The wellness industry is booming. One of the main selling points of many influencers, diets, supplements etc is trying to boost immunity. In the face of kids who seem to constantly bounce from one cough or cold to the next, child health providers are increasingly facing questions from worried parents as to what they can do to help strengthen their child’s immunity to ward off infection. As kids go back to school and the inevitable onslaught of infections begin again, no doubt these questions will be on people’s minds.

Our new review for the European Society of Paediatric Infectious Diseases (ESPID), published in the Paediatric Infectious Diseases Journal, takes a look at the evidence behind these non-pharmaceutical methods such as diet, exercise and supplements to “boost” children’s immunity.

Let me tell you what we found.

Can I boost my child’s immunity with diet or supplements?

The short answer is no.

Despite what you might read on the bottle of various different supplements or health foods, there is no clinical evidence that in otherwise healthy children, any of these things makes one jot of difference to the function of a child’s immune system or how frequently they experience infections. The caveat to this is that much of the evidence investigating this topic is of woeful quality, so even if it were the case, it might be difficult to discern from the sea of poorly conducted and reported studies that have been performed.

That is not at all to say diet and nutrition are not important for the proper functioning of the immune system. This is made very apparent in the one area where evidence is strong and plentiful; malnutrition.

In environments where children lack access to a whole and balanced diet, there is clear evidence that this drastically impacts their ability to fight infection. Frequent infections in turn negatively impact the ability of children to maintain a nutritionally replete diet, due to increased metabolic demand and poor absorption from gastrointestinal illness.

This should not be a surprise. Your immune system, like the rest of your body, needs fuel and nutritional building blocks to maintain itself. These are delivered from your diet. Whilst the body is remarkable in its ability to prioritise, adapt, and find work arounds to these restrictions, there are limits to this flexibility. Beyond a point, the immune system, like the rest of your body, will cease to function properly when it is deprived of these essential elements.

A particularly key element appears to be Zinc. In communities known to be high risk of zinc deficiency in Asia, supplementation appeared to have a clinically evident impact in reducing the frequency of respiratory tract infections. Note - rates of zinc deficiency in children in the USA are <4%, and would not be expected to routinely benefit from zinc supplementation.

Another noteworthy example is vitamin D. Despite knowledge of its molecular role in normal immune function, and observational evidence supporting the role of vitamin D supplementation in a myriad of conditions, supplementation in children showed no significant difference in any clinical immunological scenario. Vitamin D supplementation is perhaps the most famous example of an intervention which consistently shows benefit in observational data only to be found ineffective in clinical trials (to re-emphasise, this is in populations who would not be considered vitamin D deficient. There is good reason to take supplements if you do not already have normal levels of vitamin D).

Why are people allowed to advertise things which clearly don’t work? In the US, the answer is the Dietary Supplement Health and Education Act of 1994. For some reason, the decision here was to class supplements as food rather than medicine. As a result, no one has to show the FDA a product works, or is safe, before selling it. All that is required is some small print on the back of the bottle; “this statement has not been evaluated by the FDA”. UK rules are tighter on wording, but the result is the same: no trial is required to sell your product. The result is evidence free advertising.

Interestingly, obesity also appears to have immune modifying effects. The tissues comprising body fat (adipose) have relatively strong hormonal influences and are pro-inflammatory, and may increase rates of atopic (allergic) type diseases.

A healthy diet is the key to a healthy immune system, much like it is to a healthy everything.

What about exercise?

The story here is much the same.

Exercise which is excessively high or low does appear to have some immune modifying effects (interestingly intense exercise may have some pro and anti-inflammatory effects), but healthy levels of exercise seem well correlated with good immune function. Linked to the impact of diet, exercise may well help maintain a healthy immune system by preventing obesity (as mentioned above).

There are a myriad of reasons why it is good for children to exercise far beyond the impact on the immune system, but it is encouraging to think that children undertaking healthy levels of exercise get to benefit their immune system too.

What should I do?

If you are a parent, you know that your child should have a balanced diet (as much as possible!) and get regular exercise. So what to do if they still keep getting sick despite that?

There are two key things to remember: First, vaccination is the only proven way of helping protect children against common infections, and it is extremely effective. Where this is recommended for your child, accept it. Second, it is completely normal for children to get many infections, and it is unavoidable. I have covered this in more detail in a previous post, which hopefully provides some reassurance.

Summary

A healthy diet and healthy levels of exercise support the proper functioning of children’s immune systems. If your child has a relatively balanced and complete diet, there is no benefit to their immune system from taking additional supplements. The reason so many supplements or items claim to boost the immune system is that these markets are almost completely unregulated, and people are able to make a lot of money without having to provide the levels of evidence you would need for pharmaceuticals. There are many good reasons for children to have healthy diets and to exercise; consider a well functioning immune system just one extra.

The US vaccination schedule could be considered to have a reputation as “maximalist”, recommending more vaccines for children than most high income countries. There are occasions I have been critical of it, including its approach to Covid-19 vaccines for children which were so over-zealous that I believe it damaged the credibility of the agencies recommending it.

Perhaps then there is room for improvement? Last week the office of the US President issued an Executive Order regarding the childhood immunisation schedule in the US. I try not to wade into politics, but this Executive Order covers areas of science within my specialty (vaccines) which are worth addressing.

What happened?

An Executive Order (EO) is simply directions from the White House to existing agencies instructing them how to use powers they already have. It doesn’t do anything itself, but is designed to guide other agencies in how to act.

This EO is aimed at the department of Health and Human Services (HHS) predominantly, with instructions for how to amend the childhood immunisation schedule. There is preamble about how the US offers more vaccines to children than other comparable high income countries and several references throughout the document to, “Gold Standard Science” (it is not clear what this means).

The EO recommends splitting the schedule into three parts:

• Recommended for all children; measles, mumps, rubella, diphtheria, tetanus, pertussis, polio, Hib, pneumococcal disease, HPV and varicella. Eleven diseases, down from the eighteen the CDC recommended in 2024.

• Recommended for high risk groups; RSV monoclonal antibodies, hepatitis A, hepatitis B, meningococcal B, meningococcal ACWY and dengue.

• Shared decision making; hepatitis A, hepatitis B, rotavirus, meningococcal disease, influenza and COVID-19.

Then, in a single sentence the EO also recommends that the MMR vaccine be split into its three constituent components and that all childhood vaccines (including components of the MMR) should be offered at separate visits.

There are additional points regarding the way state legislatures handle religious and other exemptions among other things which I won’t go into here.

The EO itself does not accomplish anything and is not legally binding. It is noteworthy that it does not address the federal agencies that are actually responsible for setting the vaccine schedule; the Advisory Committee on Immunization Practices (ACIP) who recommend what the schedule should be, and the CDC who signs it off. This signature triggers Vaccines for Children eligibility and no-cost-sharing under the Affordable Care Act which is how children actually access the vaccines.

Analysis

The US vaccine schedule has elements to it I don’t believe are high value, such as recommending annual Covid-19 vaccination to all children aged 6 months and older (now under shared decision making). The UK doesn’t offer it at all to otherwise healthy children, and has never offered it to children <5y (which is true for many high income countries). Recommending three doses of a vaccine to a 2 year old for a virus that people can see is no different to other routine respiratory viruses for them was never going to land well. The poor uptake was predictable.

I also believe vaccine mandates are ultimately a bad idea. They increase uptake in the short term at the cost of decreasing trust overall. That said, once they are in place, repealing them is dangerous as it is likely to imply lack of confidence in vaccination and lower uptake further.

Whilst it is good to consider how the US vaccine program could be improved, this EO does not help and in fact has several catastrophic blunders in it.

Meningococcal disease as “Shared decision making”

Until the advent of the highly effective and safe conjugate vaccines, Meningococcus was a scourge of children’s hospitals. It is a devastating illness which can cause rapid onset sepsis and/or meningitis, resulting in death, disability or loss of limbs. It still occurs, but is now so rare that new resident doctors never have seen a case.

The MenACWY vaccines are particularly excellent, because they are sterilising. They prevent you from carrying the bacteria harmlessly in your throat, thereby preventing it being passed to others. You can essentially get rid of the bacteria from circulation by vaccinating groups who are known to carry it most; teenagers. Failing to vaccinate a high enough proportion of teenagers to Meningococcal serogroups A,C, W and Y would almost certainly lead to an increase in circulation and more death and disability of infants and young adults. The HHS assessment briefing document which compares the US vaccination program to other “comparable” nations showed that 15 of the 20 other nations already recommend meningococcal vaccination to all children.

For a vaccine with one of the best safety and reactogenicity profiles, moving it from recommended to shared decision making is a needless risk to take.

But it gets worse.

Splitting the MMR

For an EO with a large focus on the number of vaccine doses US children receive, it seems unfathomable that they would make a recommendation to needlessly increase the number of doses children would receive by splitting MMR into three separate injections.

No justification is given in the EO for the recommendation to split MMR (other than it is based on “Gold Standard Science”), but the signing ceremony for the EO addressed the issue by referencing “Autism in particular”. This is absurd. Far from being based on science, this runs counter to all of the research conducted to investigate this issue since the completely fraudulent publication by struck-off physician Andrew Wakefield.

I want to be completely clear on this: No research has ever demonstrated a causal link between the MMR vaccine and autism, and certainly no research has ever suggested that splitting this into three separate components would be any different. To the contrary, abundant high quality evidence has consistently failed to show any causal link between the MMR vaccine and autism. The point was originally raised by Wakefield who had himself patented a single dose measles vaccine and stood to profit enormously from his own falsified claims.

For further background on measles and its vaccine you can read here.

Worse, as one would expect, we know that splitting this vaccine into separate components reduces uptake. Trying to suggest such a thing at a time when the US is battling frequent measles outbreaks and is almost certain to lose its measles elimination status this year is disastrous.

In a welcome response to this bewildering recommendation, neither of the two manufacturers of the MMR vaccine (Merck and GSK) has indicated any intention of manufacturing split component vaccines, due to the evidence of the safety and efficacy of current products and known harms of splitting it into several different shots. Hopefully this will simply become impossible to push any further because the product will not exist.

Separate visits

Not only are extra injections being recommended by splitting the MMR into three components, but in the same sentence, they recommend all vaccines are administered at separate healthcare visits. This would mean for infants in the US who would currently receive their infant vaccines in 3 different visits at age 2, 4 and 6 months, they would need to attend up to sixteen different healthcare appointments to receive the same number of vaccinations.

Once more, no justification is provided in the text. We again only have comments made during the signing ceremony, referencing the volume of vaccine being administered to children as comparable to a bottle of soda (simple maths tells us the maximum cumulative volume administered to a child up to the age of 18 who received all recommended vaccines to be ~30mL). The implications of this, or why it would be preferred to administer the trivial amounts of fluid received via the vaccines (~0.5mL per injection) over separate visits is unclear. This recommendation is unfeasible in practice and would result in significantly reduced vaccine uptake as even the most willing families would struggle to attend so many appointments.

Failing on its own merit

The premise of the EO is misguided. Comparing geographically small and homogenous countries like the UK, Sweden or Denmark to a country the size of a continent with a diverse array of communicable disease threats doesn’t make sense. What makes more sense is to approach each individual vaccine recommendation and evaluate it on its own merit. I will not do that here as that is a task worthy of a dedicated task force (hence countries providing their own task force such as ACIP or the JCVI).

For now, let us take the high income country the US is most comparable to - the UK. There are few differences in diseases covered by the US and UK. These include Hepatitis A, of which the UK has close to zero locally acquired cases and the US used to experience frequent outbreaks until routine immunisation. Or dengue, which occurs in particular regions of the US and is not endemic anywhere in the UK. Or the BCG, which the UK does offer for high risk populations and the US doesn’t at all.

In fact, to become more US-like (in a positive way) UK is adding more diseases to its schedule. We have just added another component to the MMR (Varicella into the now MMRV). We are also adding in an adolescent MenB vaccine (and already offer an infant MenB dose beyond the US).

The big differences are that the UK delivers several multi-component vaccines such as the 6-in-1 infant vaccine (Hib, DTaP, Polio, HepB), and has reduced the number of doses administered of some vaccines such as the HPV vaccine (down from 3 to 1) and the Pneumococcal vaccine (down from 3 to 2). Remember this point.

It is worth noting despite this, that in the document the HHS uses as its assessment underlying the comparison to other countries, the new recommendation wouldn’t bring the US in line with other countries; it would drop it to among the lowest of any comparable nation despite it being so huge and geographically diverse, and having health systems in no way comparable to e.g., Denmark, which would be the only country recommending fewer vaccinations. Based on the EO, the US would recommend vaccinations against fewer diseases than Guinea-Bissau.

Incredibly, the HHS review document actually recommends giving more multivalent vaccines to reduce the number of injections required - the opposite of what the EO is now suggesting for MMR.

This EO which wishes to reduce the number of injections children in the US receive seems set to only increase the required number of injections and increase the total volume of vaccine administered. It is a document which defeats its own stated goals through its own recommendations, and in spite of a briefing document which recommends precisely the opposite approach.

If the aim is to consolidate what could be seen as an unwieldy schedule, this could be considered laudable. If you try to pack too much in, you risk reducing uptake which is the cornerstone of successful vaccine policy (especially where herd immunity is at play). Following the UK in simplifying the schedule for certain diseases by reducing the number of doses, and increasing the number of multivalent injections would be the perfect solution and would reduce the number of injections by more than thirty1. I would recommend it. The HHS reference document even hints at it. Instead, the EO has recommended the opposite.

What happens next?

Based on the considerable existing evidence around these vaccines and their implementation, the most likely outcome of these recommendations being implemented would be to reduce vaccine coverage among the population and a resulting increase in vaccine preventable disease.

The only justification given for splitting MMR flies directly in the face of the extensive scientific evidence which shows no link to autism, and instead leans on unethical, fraudulent research which was exposed over 20 years ago.

Given the previous mess that the HHS made of ACIP and the extensive legal entanglements which continue in the wake of this, the lack of any split MMR products to even administer, and the extensive pushback the EO has already received from other lawmakers in the US, it’s not clear what will practically change in the US as a result.

What will likely continue to change is the erosion of trust in vaccines and the vaccine schedule in a country which is already seeing the consequences of playing political games with the health of children. They continue to be the ones set to lose.

The White House has clearly been grossly misled about the state of the scientific evidence on these basic vaccination safety and efficacy issues. The people providing this false and misleading information are doing a disservice to the children of the US, and these actions are an embarrassment to the governing administration. It is not too late to change course.

Following my recent article on an RCT of air filters in care homes which failed to demonstrate a meaningful reduction in infections, I read an opposing viewpoint from a scientist from a chemical engineering background1.

The key point was that RCTs are meaningless for these technologies, and what really matters is measuring levels of infectious pathogens in the air in the rooms around the residents.

I have seen similar viewpoints echoed from several people among the engineering community stating RCTs are the wrong way of assessing technology such as air filters. There are essentially two approaches here, and they are viewing it through the wrong lens. Let me address some specific points.

RCTs measure the wrong thing

This was the main point of the first essay. It is argued that the appropriate outcome for such a study is simply to measure how much infectious material was in the room where the filter was placed.

The cornerstone of the argument as to why the RCT was flawed, is that the filters would only be effective if the residents were forced to stay inside the room with the filter on for the duration of the experiment. Since they did not, there was no point measuring how many infections they had and the RCT was a waste of time.

This argument is completely backwards.

Measuring infectious pathogens in the air is not the thing we are actually interested in. This only matters insofar as it leads to symptomatic infections. Symptomatic infections are the primary outcome of interest, and infectious pathogens in the air are only a surrogate marker - something we would anticipate to be correlated with the thing of interest, but not the thing of interest itself. There is no point in measuring a surrogate if you can measure the main outcome of interest. In fact, this is always the wrong thing to do.

If the residents spend almost no time in the rooms, and therefore the filters have no opportunity to have any effect, this has given you your answer! There is no point putting the devices in the residents rooms. If the residents constantly turn the machine off because they are too noisy, this has given you your answer! The machine is useless because it is intolerable.

The conclusion here is precisely the opposite of what is argued. It is excellent that we did not just measure the surrogate outcome, or else we might have concluded the residents were benefitting from a measured reduction in pathogen load. As it turns out, they couldn’t tolerate having them turned on and didn’t spend any time near them, and so investing in them would not be a good idea. We only know this because we did the RCT.

Finding a negative outcome because the machines were not used correctly is a feature and not a bug of the RCT.

Human beings are complex, and when exposed to technologies can behave in unexpected (or in this case, perhaps expected) ways. When you add distance between this mechanical effect and the desired outcome, such as patient adherence or complicated biological pathways, RCTs become even more important.

The case was exactly the same for community masks. Of course we shouldn’t expect huge benefits when they have to be removed to eat and socialise, as these are the highest risk encounters. Imagine a condom that you are made to wear all the time, but for practical reasons has to be removed during sex. We would not expect good protection when the barrier has to be removed during the most high risk encounters. These types of questions cannot be answered by simply testing machines in a lab, or measuring levels of pathogens either side of a barrier.

When done correctly, a clinical trial should always measure the final clinical endpoint that we are most interested in, or at least get as close to it as possible. If the thing you really care about is the number of infections, measure those. Measuring anything else makes it a worse study. We should never care about surrogate outcomes when we can measure the thing that really matters, and whether it changes or does not, it renders the surrogate outcomes meaningless.

We don’t need RCTs for fridges

The first comparison made is with fridges. We do not do RCTs of fridges stopping people getting sick, we simply measure pathogen loads at different temperatures.

This argument misses that the point of fridges isn’t actually to stop people getting sick, but to make foods last longer. This is directly measurable by pathogen load; it is not a surrogate.

It would actually be very easy to do an RCT of fridges stopping people getting sick; give two groups of people an uncooked chicken for 7d, with one group in the fridge and the other out in the garden. Then force both groups to eat the chicken. We would not struggle to find a meaningful difference! The causal chain here is so short that the RCT becomes unnecessary. The outcome is inevitable. This has been shown to be far from the case in trying to implement masks or air filters.

We don’t need RCTs for handwashing

A different counter-example was handwashing. The author points to some RCTs that were done for handwashing, and failed to find an important difference.

This doesn’t surprise me at all.

At modern levels of hygiene, handwashing almost certainly makes a trivial, if any difference to disease transmission in most settings. The scenario in which it was originally discovered to be beneficial involved doctors moving immediately from examining dead, festering corpses, to delivering babies. Enormous inoculations of highly pathogenic bacteria directly into open wounds. This is hardly the scenario we would expect to find ourselves in today.

Why then do we still recommend it? Again, there is a very short causal chain; albeit at very low risk. But importantly, it is a behavioural intervention with effectively zero cost. Almost any conceivable benefit at all would make it worthwhile. Simply making people to stop and think about cleanliness of their hands is probably worth it, because it costs nothing. It is similar with asking people to sneeze into their elbows. Does it work? Possibly. But it costs nothing, so might as well ask people to do it. This is very much unlike the cost of retroactively installing hundreds of millions of pounds worth of air filtering devices into institutions around the country.

The Two Approaches

We need to understand there are two valid approaches to using interventions like this technology.

The first is to decide there is likely a large, measurable benefit which is worth rapid investment of very large sums of money. Such a proposal requires an RCT to evaluate it, otherwise huge sums are spent on a wasted endeavour. During and post-pandemic, many advocates of clean air framed the debate in this manner, hence the RCTs were performed. I’m sure they are disappointed to see the negative results, as we all are. However, it does show that doing RCTs to evaluate such claims was the right decision.

If you want people to rapidly, and at great cost, install your technology, then they will expect effect sizes which should be easy to measure in an RCT.

The alternative, and in my opinion, correct approach, is to suggest that such technology probably provides marginal benefits which would be difficult to measure in the short term, but over many years and over large populations probably provide a worthwhile benefit.

Such claims are extremely difficult to evaluate in an RCT, but can be evaluated on the merit of existing mechanical evidence and such surrogate markers, and the decision point is different. There is no huge urgency in such a case to retroactively fit devices wherever we can squeeze them in. Instead, we look at things like reforming building codes to include more emphasis on ventilation and clean air, and provide incentives for institutions to proactively upgrade systems over time when the opportunities arise.

The well intentioned, but misguided advocates for clean air during the pandemic have perhaps had their actions backfire. Messages like, “air is the new poop”, or “clean air like clean water”, or that they could effectively end the pandemic, have set impossible expectations for these technologies. That should not lead us to believe they are worthless. Clean air for health is deserving of much more attention. We simply need to refocus our efforts on policies and methods of implementation which are befitting of the magnitude and timelines over which we would expect to see benefits.

1

You can read the two articles here:

Matters of Perspective

Air cleaning technologies and the battle against Randomised Control Trials

A recent paper in JAMA reported the conclusion of a large scale RCT trial on the use of portable HEPA filters in care homes. The study found little significant evidence that they helped reduce infections, and although there have been numerous criticisms of the study, most of these have focused on the lack of rigour in ensuring adequate effective air cha…

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a month ago · 20 likes · 6 comments · Dr. Nicola Jane Boyd

Matters of Perspective

Air cleaning technologies and the battle against Randomised Control Trials – Part II

Yesterday I published my critique of the recent JAMA paper regarding the RCT results on the use of HEPA filters in care homes. Unfortunately what I have termed the ‘dogma creep’ that demands the use of RCTs for inappropriate applications is extending into the safe air campaign sector too…

Read more

a month ago · 4 likes · Dr. Nicola Jane Boyd

Many topics during the pandemic seemed to become almost impossible to have reasonable debates or discussions about, and one of the more surprising topics was air filtration. This took the standard dynamic of a determined group on one side citing overly optimistic predictions of its efficacy, and another stating that the whole endeavour was utterly useless. Sadly, we lacked much evidence of the effectiveness of the implementation of such systems at the time, but hoped that as new evidence emerged it might help make the debate more sensible.

Alas, the topic still seems to result in people losing their heads, as we have discovered with the publication of a new RCT.

Let’s take a look.

What is the study?

The study was conducted by a well respected team from Bristol in the UK. They conducted a cluster randomised controlled trial of air filtration devices in care homes; meaning that randomisation occurred at the level of the care-home, not of the individuals within it.

This type of study has a higher likelihood of showing benefit than randomising individuals. When one person avoids an infection, they protect the people around them from the infections they would have otherwise caught. Multiple people within the care home being protected should produce a larger signal, which is easier to detect in a trial.

The intervention was the introduction of up to 5 air filtration devices into communal areas and up to 16 into the bedrooms of residents, compared to care homes acting as controls that did not introduce air filtration devices.

Unlike previous trials, the study had, in my opinion, a robust statistical design that was powered to detect a reduction of one infection per 242 care home days, with sufficient recruitment to account for residents who did not wish to participate, moved on, etc. As such, an impressive 91 care homes were recruited with over 1000 residents contributing data.

By the end of the study, there was not a significant difference in the number of respiratory infections in the residents of care homes with filtration devices and those without (0.99 vs 1.04, p=0.67), nor a difference in rates of absenteeism in staff, antibiotic use, etc. The study authors acknowledged there are other benefits to air filtration outside of any use for preventing respiratory infections.

Why the controversy?

Many people have advocated strongly for the introduction of air filtration devices into shared spaces such as care homes and schools, and the response from some groups towards the study has not been positive.

Many experts in air filtration have rightly pointed out some limitations in concluding that air filtration does nothing on the basis of this study, such as the units being small, often used on the lowest setting or turned off by residents, and that we don’t know where they were placed or other factors that could impact how effective they are. The implication here is that if big enough filtration devices are used properly, located in the correct place, and turned on all the time, then they are much more likely to show an impact.

This may be true, but this raises a new and important point. If it is that difficult to get people to use these machines in a way that actually provides benefit, then they are useless. It is like suggesting that a medication that needs to be taken 11 times a day, not within 2 hours of food, and causes explosive diarrhoea is highly effective as long as patients take it precisely according to instructions.

A key part of the efficacy of an intervention is how easy it is for people to adhere to the intervention. If it is too noisy, too sensitive to positioning, or too easy to urinate into (this did unfortunately occur during the RCT), then it is no good. One commentator suggested filtration devices should be placed immediately next to residents when they are sick in order to be effective; an idea I don’t think many care home residents would find appealing.

At this stage, the most positive argument for the use of air filtration is to have it embedded prospectively in new buildings with the appropriate specification (so long as this doesn’t prove prohibitively loud).

This is the best available evidence on this topic so far, and as the authors point out, it is consistent with systematic reviews which have not found evidence of efficacy.

It looks to me from all the available evidence so far that retrofitting these devices in public spaces provides little to no benefit in reducing rates of infection. There are other benefits to air filtration, such as reducing pollution and aeroallergens, but these need to be weighed against the significant costs of purchasing, installing, and running such devices in an already stretched public sector. Estimates are that it would cost >£150 million to install such HEPA filters in care homes across the UK.

This is not to say institutions such as care homes or schools should not install such devices, but would suggest large-sale retrofitting projects are probably not a good use of funds for this purpose.

For more on the difficulty of controlling infections that move through the air, and why they are not comparable to controlling infections that spread through water, you can read a previous post on the topic here.

Neonates are a highly vulnerable population. The mortality risk in the first 24h of life is greater than any other 24h period, and a substantial portion of this risk is from infection. As such, most countries take a highly risk-averse position on investigating and treating for so-called Early Onset Sepsis (EOS).

This is not without consequence. High numbers of infants who may not be very unwell are admitted for intravenous antibiotics. For a risk of EOS that affects only 0.5 - 1% of live births, we end up treating up to 1 in 6 babies with antibiotics. Besides the stress and inconvenience this places on mothers and families at an already challenging time, there is growing concern over the impact of early life exposure to antibiotics on the infant microbiome and how this might affect later life risks of inflammatory, atopic, or autoimmune disease.

This risk aversion has also made it difficult to get much high quality research done in this area, but there have been a couple of huge steps forward in the past few years.

Let’s take a look at these some new studies and what they mean.

RAIN

In 2022 the Netherlands based “Reduction of intravenous Antibiotics In Neonates (RAIN)” study, looked at whether it was safe to switch neonates with negative blood cultures (no evidence of bacteria in the blood) from the usual intravenous (IV) antibiotics to oral antibiotics. This is a bigger step than it might seem, as there is a historical hesitation to use oral medications in very young babies due to concerns their gut won’t absorb them well enough.

Eventually 510 babies with probable bacterial infection (for example, symptoms or raised inflammatory markers such as CRP) were randomised to a full course of 7 days IV antibiotics or to switch to oral Co-amoxiclav. After the follow up, there was no difference in adverse events in either group nor any difference in the number of babies re-admitted for suspected infection (<1% in each group), and the babies who were switched to oral antibiotics were able to be discharged from hospital 3 days sooner.

So did everyone start switching these high risk babies to oral antibiotics? Sadly not. Some people will never be convinced oral antibiotics are just as effective as IV antibiotics; but some made a different point. Perhaps the reason it doesn’t matter if you switch to oral antibiotics or not, is that most of these babies don’t need any antibiotics at all. A bold suggestion!

But now we have some data to test it.

DURATION

A brand new trial has just been published out of Denmark looking at whether all these high risk babies with negative blood cultures need to receive a full course of 7d of antibiotics, or might be able to stop completely.

They randomised nearly 500 babies to either receive 7 days of antibiotics (including an oral switch by the way), or to receive individualised care; in this case, the antibiotics were stopped completely once the baby had no symptoms of infection for >24h and their inflammatory markers in the blood (CRP) were below 30.

Once again the finding was that the intervention was non-inferior for readmission due to bacterial infection (≤1% in each group), and there was a substantial reduction in the number of days of antibiotics given to the individual care group - by four days.

What does this mean?

Neonates are still a high risk population, and they are worthy of a high degree of caution. However, the feeling among many infectious disease specialists (including myself) and many neonatologists is that the pendulum has swung deep into the over-cautious territory (often due to highly risk averse guidelines). This is not what is best for the infants, and need to find safe ways of reducing the level of invasive interventions and antibiotic exposure to them in the first days of life.

Getting babies home sooner is a quick win, and switching babies with suspected sepsis and negative blood cultures to oral antibiotics is clearly safe. Furthermore, in babies who are no longer symptomatic and their inflammatory markers have reduced it is almost certainly safe to stop completely.

Stopping antibiotics as early as possible helps enable families to start settling into their new normality sooner. It also reduces the potential risks of antibiotic exposure in a cohort who have an immune system trying to learn what is friend and foe.

We are currently treating too many babies with antibiotics, and for too long. The evidence is clear that there are things we can change now to improve care for these infants, and they deserve better than lengthy delays in changing practice.

In March of this year the UK experienced its largest ever outbreak of MenB within a university population in Kent. Two young people died and over 20 were affected. This led to renewed interest in the issue of vaccinating this population, which had previously been found not cost effective by the UK vaccine advisory panel, the Joint Committee on Vaccination and Immunisation (JCVI). You can read more about the outbreak and the background to the MenB vaccine in my previous coverage.

Yesterday however the JCVI had published a new statement formally recommending vaccination for teenagers. This news will be welcomed by many health professionals (including myself), as well as many anxious parents. But how did this come about?

The background is more interesting and complicated than you might think, and three things in particular have given me some pause for thought.

The JCVI statement

You can read the statement from the JCVI in full here, but we will focus on what has changed the recommendation.

I will start with the most important. The JCVI have been shown evidence from the vaccine manufacturers that giving a single dose to teenagers who had previously been vaccinated as infants appears to provide robust protection (presumably in the form of measurable antibody responses).

Previously it had been considered that two doses were necessary to provide meaningful protection. Being able to give one dose instead of two will almost halve the cost of the entire program. Half the number of vaccine purchased, half the number of nursing visits, half the number of consumables, etc. This is directly applicable to children born in the UK from 2015 onwards who will have been offered the infant MenB vaccine as part of the routine immunisation schedule. This alone is probably the main determining factor.

The JCVI point to some other considerations. There is now reasonable evidence that protection from the MenB vaccines extends out to at least 5 years. This is enough to give a programme to teenagers at school and cover them through the early years of university - the highest risk period by far. This evidence is uncontroversial.

They also reference the additional benefit of the vaccine in protecting against Gonorrhoea, citing observational evidence of up to 40% protection. This isn’t new, and JCVI have in fact been recommending MenB for other cohorts at risk of Gonococcal disease since 2023.

It remains the case that the MenB vaccine does not provide herd immunity as it does not prevent carriage of the meningococcus (unlike the MenACWY vaccines).

What will happen next?

The JCVI had already recommended a “one off” campaign this year for 18 year olds, which will still go ahead. Next is for the government to consider the recommendations, which are as follows:

• Teenagers who received the infant MenB schedule (born from 2015 onwards) to get one dose of 4CMenB when ~15 years old

• Teenagers who were eligible for the infant MenB schedule but didn’t get it to receive two doses of 4CMenB

• Teenagers born before they were eligible for the infant MenB schedule to get two doses anyway, on the grounds of equity

• A catch up campaign to cover teenagers who weren’t eligible for the one-off campaign this year and who might miss the new program

The government is likely to accept this recommendation. The secretary of state called an extraordinary meeting with JCVI following the outbreak in March to re-evaluate it, and politically it is a savvy move at a time when many voters will be anxious about the disease.

This is interesting to contrast with the position in the US, where adolescent MenB is already recommended for 16 to 23 year olds under “shared decision making” (uptake has therefore been predictably quite low), but has never introduced routine infant MenB vaccination. This is almost the inverse of the current UK schedule, and following the new recommendation the UK may end up being more bullish on MenB than the US.

Some things to ponder

I am pleased that adolescents in the UK will now be vaccinated against MenB, and it will have a material impact on case numbers (albeit, these are already relatively small with around one case of MenB across all populations per day in the UK).

There are some parts of the JCVI statement which have made me pause for thought. The first is that the primary driver of the change is the single dose decision, which is based entirely on data provided by the drug manufacturer and remains unpublished. I am not as distrustful of the pharmaceutical industry as many, but clearly this is not the optimum circumstances for JCVI to make the decision. They are well aware of this, stating, “Timely publication of this evidence is strongly encouraged by JCVI.”

Hopefully this will be forthcoming soon and will satisfy this anxiety.

Next, it is not clear to me that the MenB vaccine protects against gonorrhoea. Whilst the observational evidence for this looked promising, there are now several randomised controlled trials (two small studies in Nature and IJID but most robustly in NEJM) which have found no evidence of protection. This is disappointing news, but does raise a question over its inclusion in the analysis, which apparently is an assumption the modelling was very sensitive to. The JCVI make note of this discrepancy, but are more dismissive of the NEJM RCT from Australia given the very high risk population it was conducted in, citing this making it less generalisable to the UK adolescent cohort.

Finally, there was an unconventional decision by the JCVI to include “peace of mind”, as one of the factors in their cost effectiveness analysis. This is unusual, as including this has historically been considered and dismissed due to the inherent difficulty in providing meaningful estimates for how to cost it. It was brought for debate in consideration of the original infant MenB programme (which had been found to be not cost effective at any price), and was advocated for by the Meningitis Research Foundation.

A whole new subcommittee was formed to consider this topic (Cost-Effectiveness Methodology for Immunisation Programmes and Procurement, or CEMIPP), and in 2019 their recommendations for this were rejected. This was alongside a number of other recommendations which actually would have made it more difficult for vaccines to cross over the cost-effectiveness threshold, and eventually the MRF petitioned the government to reject the findings themselves.

The details of how “peace of mind” was costed are not included in the statement, and the full modelling by Bristol, UKHSA and Imperial is unpublished (it’s not clear whether this was a single study done in collaboration or whether there are several complementary modelling studies).

The inclusion of “peace of mind” is also contrasted with the decision not to include any other wider societal benefits (e.g., school attendance) as part of the cost effectiveness analysis in accordance with the JCVI Code of Practice.

This is not to say such a consideration is not legitimate, and methods clearly evolve over time - but it is noteworthy that it was used in this scenario.

Summary

The JCVI have recommended the MenB vaccine as a predominantly single dose schedule for teenagers aged 15 who previously received the infant schedule, although other teenagers will also be offered two doses. The government is likely to accept these recommendations. The change in position from JCVI is likely mostly due to new evidence of the efficacy of a single dose in previously primed teenagers, but other assumptions in the modelling seem less traditional and some perhaps less robust. We now await the decision by the government, and publication in full of some of the contributing evidence.

When your child is feeling unwell with fevers, one of the most striking features that may occur is the onset of a rash. This is a common cause of alarm among parents and a frequent reason for attending the emergency department. Fortunately, most of these rashes are completely benign and require no intervention; but how are parents supposed to know the difference?

Let’s walk through the issue together and bust some myths along the way!

The non-blanching rash

Let’s start with the rash which doctors will always want to review your child for. Almost all of the benign rashes share the same feature, which is that they blanch. This is indicative that the redness is caused by inflammation in the skin, and by an immune response to some other pathogen. The commonly known way of assessing this is the glass test - pressing a glass on the skin and seeing if the redness subsides. You can also stretch the skin for the same effect, and in practice I find this is actually much easier.

When a rash does not blanch, this is a sign of a different underlying cause. This indicates that blood has left the tiny blood vessels known as capillaries, and what you are seeing is actually tiny little bruises. When these spots are very small, we call them petechiae. When they get larger and start to coalesce, we call this purpura. At this point it looks like large bruises.

The most common cause of petechiae is just a viral infection, so it is probably nothing serious - however there is now enough of a chance that the rash is caused by something worth knowing about that a doctor would want to see them and probably do some basic blood tests.

The famous cause of this type of rash is Meningococcal septicaemia; a blood stream infection caused by Neisseria meningitidis, the bacteria famous for causing sepsis and meningitis. It was this bacteria that led to the highly successful awareness campaign around the glass test.

Thanks to the success of vaccination, it is now extremely rare for these rashes to be caused by Meningococcus. The latest studies suggest ~1% of all cases are attributable to this, with other invasive bacterial infections now being more common than Meningococcus, and benign viral infections being substantially more common than both. This is especially the case for petechiae; for purpura, the rates of Meningococcal disease and other invasive bacterial infections is much higher, and febrile children with purpura should be treated as though they have meningococcal disease until it can be proven otherwise.

It is worth doing blood tests for children with petechiae to investigate for Immune Thrombocytopaenic Purpura (ITP), which is a relatively benign condition when the immune system temporarily targets and consumes the small cells known as platelets which help your blood to clot. In very rare instances, non-blanching rashes with fever can also be the presenting symptom of leukaemia. Whilst being very rare, it is simple enough to rule this out with a quick blood test and is worth doing.

The Viral Exanthem

When kids are unwell with febrile illnesses, there are several different reasons a rash can occur but one of these is by far the most common. The type of rash we call, “viral exanthem”, occurs frequently during a multitude of different childhood viral illnesses being caused by several different pathogens. This category broadly covers the widespread, red, blotchy rash than can occur all over the body, and has the notable feature of being blanching (as discussed above).

The true biology behind why these rashes occur is not well known, but it appears to be a side effect of the immune response to the infection. The skin being the largest organ in the body means that it is often first to get caught in the cross-hairs when the immune system gets a little over-active.

The important thing about viral exanthems, is that despite having such a fancy name, they are almost completely benign, and absolutely no intervention is required.

There are multiple specific syndromes which can be diagnosed under this umbrella, but it is usually irrelevant (save a couple of cases mentioned below). Whether the child has Roseola, Slapped cheek syndrome, or some random enterovirus or adenovirus doesn’t change the fact that there is no effective treatment available, or needed, as these conditions are all benign and self limiting.

There are only two exceptions to this:

Measles: What used to be one of the most common and dangerous causes of viral exanthems in children is now relatively rare, but sadly, is becoming increasingly less rare in many western countries. If you suspect your child has measles, they absolutely must be seen by a health professional. It is a potentially dangerous infection, and it is important that public health authorities are able to trace and contain potential exposures. The most important risk factors for measles are vaccination history and known/possible exposure. The three C’s precede the rash (cough, coryza, conjunctivitis). It’s a shame this is even worth mentioning, but that is the world we are now living in.

The Munro Report

The Misery: Return of Measles

“Are you feeling all right?” I asked her…

Read more

3 years ago · 19 likes · 3 comments · Alasdair Munro

Scarlet Fever: This falls into the category of viral exanthems for historical reasons, despite actually being caused by a bacteria - Group A Strep (GAS). This infection is not dangerous, but is caused by a strain of GAS which produces toxins and is associated with outbreaks of invasive disease. The hallmarks of scarlet fever are the sandpaper-like touch of the rash, which has a very rough texture to the skin, alongside a strawberry tongue. This is worth treating to prevent spread of the toxin producing strains of the bacteria, but the infection is not considered dangerous to the child themselves.

Urticaria

Most people are aware of the rash urticaria, commonly referred to as hives. It is known for being associated with allergy; but a fact that surprises most parents it the most common cause of this rash in children is viral infection! The rash can occur during or shortly after the infection itself, and is painless but can be itchy and troublesome. The main issue is that unlike allergic urticaria, viral urticaria is not effectively treated by antihistamines. In fact, it doesn’t seem effectively treated by anything at all. This can be irritating for the family, but is not a cause of any danger.

This rash can also last a surprisingly long time; often up to a week after onset. It is rarely a cause for concern and will resolve without any intervention.

One again, the cause is likely the skin receiving friendly-fire from the immune system responding to the initial infection.

Kawasaki disease

A last word on one non-infectious cause of fever and rash worth knowing about, as early in the illness it can look indistinguishable from viral exanthem. There is a rare condition caused by inflammation of blood vessels known as Kawasaki disease. Every child with fever for 5 days or more should be reviewed by a doctor to check for the symptoms of Kawasaki disease, which include; maculopapular rash (like a viral exanthem), large cervical lymph nodes, bilateral non-purulent conjunctivitis, strawberry tongue (or other oral mucosal changes), and peeling of the skin on the hands and feet. Children with Kawasaki disease are also usually absolutely miserable.

This condition is very rare, but can result in bulging of the coronary arteries with long-term complications if not diagnosed and treated early. It’s easy enough to remember that if your child has fever for 5 days or more, you should get them checked.

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So when should I worry?

The rash is not the most important symptom. The key element is how your child seems in themselves. If they are behaving as you would expect with a usual childhood illness, then it is unlikely there is anything to worry about. If they have a blanching rash and they seem well, they probably don’t need to be seen unless you are worried they might have measles or scarlet fever.

Children with non-blanching rashes should always been seen by a doctor. It is most likely that this is still caused by a benign viral illness, but it is worth ruling out more serious causes.

Children with a fever for 5 days or more should be seen to check for the signs of Kawasaki disease, which although very rare, has complications which can be prevented if caught early.

The golden rule always applies. If your parental spidey-sense is tingling, it is always better to get them seen.

For more information on rashes, you can refer to the Healthier Together NHS page about rashes in children.

This was originally published as a guest post via the Sensible Medicine substack. I am pleased to now share it with my own subscribers, I hope you find it interesting.

Universal newborn screening with whole genome sequencing (WGS) is coming to the UK - at least on paper. There are conditions for which this would seem to clearly make sense, many for which it would be a disaster, and a vast area of grey in-between. The government has ambitious plans to roll out WGS for all newborn infants by 2035, but the practical and ethical implications of this are not ten years away.

Friends of mine are expecting their third baby, and recently that they had agreed to take part in a research study called Generation Study. This research involves performing genetic screening at birth for a selected set of 200 genetic conditions, and is being undertaken to better understand the implications of the UK governments ambitious WGS plans.

We discussed their thought process behind consenting, and then they asked me, “would you have entered your children into this study?”

I paused. Probably for longer than I should have.

Part of it is almost certainly my own philosophical biases about healthcare in childhood. But part of it is due to my apprehension about combining two topics which have great validity and simplicity at face value, but in reality are fraught with practical and ethical complexity.

Genetics

Genetics is of increasing importance within my own specialty (I am a combined paediatric immunology and infectious disease specialist), but it’s become clear it is far more complicated we previously thought. Two siblings with identical genetic mutations can have vastly differing disease phenotypes - something I witness in my clinical practice. The idea then that we can simply identify any problem with any gene and immediately predict the outcome for the patient has been proven false. Finding variants of uncertain significance (VUS) or uncommon types of mutation make interpreting many genetic results very challenging.

Despite this, it has undoubtedly brought important progress. We have children with conditions that we have understood from the ground upwards; finding a genetic VUS which has prompted more targeted functional testing of the immune pathways involved to clinch a diagnosis. These findings are not academic, but have changed the targets of our treatment.

Screening

Despite its many issues in other settings, screening also undoubtedly has huge benefits in paediatrics. In the UK we currently screen for 10 conditions using the newborn blood spot test. One of the best examples is surely Cystic Fibrosis, the most common life-limiting genetic condition in the UK, and is currently included on the newborn screening blood spot. We now have drugs which may completely re-establish normal life expectancy for children with CF (CFTR modulators), and the earlier treatment can be started the better the long-term outcomes.

The criteria for adding to the screening list in the UK are so strict that no additional conditions were added between 2015 and 2022. This makes it even more challenging to contemplate universal WGS in the next decade.

Why not combine the two?

Testing children with a specific disease phenotype for a targeted set of genes which could be implicated is uncontroversial. Performing genetics tests on a well child prior to symptom onset is a different story.

There are two ends of the spectrum. Take Spinal Muscular Atrophy as a positive example. The condition has a clean genotype with bilateral loss of the SMN1 gene, so testing will generate few false positives. The intervention window is also extremely narrow, with the new and relatively effective therapies needing to be commenced within the first few months of life to make a big difference to outcomes.

Then there are diagnoses which almost everyone would agree we should not screen for. Huntington’s disease is completely incurable, and the child’s family being aware from birth of this eventually and unavoidably lethal diagnosis is agreed by most to be unethical.

Between these two ends of the spectrum is where things get murky. There are inborn errors of immunity including within the Generation Study which result in immune dysregulation and autoinflammation which do not usually present with symptoms until later in childhood. Symptoms are then managed responsively, with some monitoring for pre-symptomatic inflammation in the interval periods. Should we be screening for these disorders? What do we do with a newborn baby who has not yet developed any symptoms of their disorder, and who would otherwise be living a normal life? Do we monitor them prior to symptom onset? Is there a role for pre-emptive anti-inflammatory treatment? These are not rhetorical, but actual clinical questions we have had to ask as children diagnosed as part of this study have come to our service.

Whilst being aware of my particular philosophical stance, I sometimes can’t help but feeling we have stolen something from the infant’s childhood by unearthing their diagnosis before its manifestation. Years spent as a family without doctors visits, without health anxiety and without labels. The sense of normality. These things are precious, and for children with genetic conditions will not be recovered once lost. Where we can be certain that taking this from a family earlier in life will improve the child’s health and longevity, it seems a worthwhile cost to bear. In some instances things are not so clear.

What is the future?

Wherever you live, genetic screening at birth to some degree seems inevitable once costs have fallen sufficiently, and they are falling rapidly. The Human Genome Project cost more than $2.5 billion by its completion over 20 years ago - we are now approaching sequencing an entire genome for $100.

There are many important questions which need to be answered about the particulars of this testing. Should we be sequencing every child’s entire genome, and if so, what do we do with the data after screening? What rights should the child have to this once they are an adult? Should we only be testing for specific conditions, and if so, which ones?

I feel that equally stringent criteria should be applied to these conditions as are currently applied to the existing screening program in the UK. There are significant harms to causing confusion and uncertainty with findings that are non-definitive. The aims when designing the program should be to maximise test specificity and to focus only on conditions where we have clear evidence that early diagnosis improves longevity and quality of life. Where this is unknown, screening should only be implemented in a limited research setting.

So would I have enrolled my children into the study if I’d had the chance? I honestly still don’t know. Would the risks of getting a diagnosis which is uncertain, or unclear if truly actionable, outweigh the potential benefits of getting a life-saving diagnosis in the first weeks of life?

I guess that’s what they call equipoise.

You may have seen headlines about a single, cheap, now withdrawn vaccine that appears to cut your risk of dementia by around a fifth; the live-attenuated shingles vaccine (now replaced by a recombinant vaccine). You likely saw it stated as plain fact from a source you trust. It is one of the most hopeful ideas in recent medicine, and as a vaccinologist, I would love it to be true.

This is why it is due more scepticism than it has received, and the last week has brought some important events.

Let’s look at the story and recent developments.

Why would anyone think this?

The underlying idea is not completely implausible. Previous lines of research suggested neurotropic herpesviruses such as Varicella zoster, the shingles virus, may play some role in dementia. If a dormant virus reactivating in the nervous system contributes to neurodegeneration, a vaccine that keeps it dormant could theoretically help.

The trouble started with studies that simply compared dementia rates in the vaccinated and unvaccinated. These reliably found lower rates in the vaccinated but are close to uninterpretable, because people who turn up for vaccines are healthier, wealthier and more health-engaged to begin with. A giveaway was that in several datasets the flu vaccine looks almost as "protective" as the shingles one. When every vaccine prevents dementia, you are not measuring vaccines. You are measuring the kind of person who gets them.

What changed things was a 2025 Nature paper from Wales. Eligibility for the live vaccine there turned on an arbitrary date-of-birth cut-off: born just before, ineligible for life; just after, eligible. People either side of that line are, on average, extremely similar except for their access to the vaccine. The design behaves somewhat like a natural experiment.

The study reported a jaw dropping 20% relative reduction in dementia over seven years. The situation presented a clever opportunity, and this was meant to be the study that finally escaped confounding. The same team then applied the same trick to rollouts in Australia and Ontario, and each time the result pointed the same way. To most observers the same finding across three countries looked like gold-standard confirmation, and was heralded as such by some.

The cracks

There were many reasons to have remained highly sceptical of these findings at the time.

The effect was enormous. A one-fifth reduction from a single jab, against a disease which, until now, we’ve struggled to even understand the pathophysiology of, let alone make any therapeutic progress, is the kind of effect size that should raise an eyebrow instead of a cheer.

It was also mostly in women, with little or no effect in men. A real biological effect confined to one sex is possible, but seems highly unlikely in a disease where the pathology is thought to be common, and seemingly scrambled explanations were put together after the result was known.

As Vinay Prasad has noted, where survival curves have been presented (showing differences in how many cases occur over time) the effect seems to occur implausibly early following vaccination. For a disease which takes years to develop and manifest, an almost immediate effect from vaccination is difficult to explain.

On a more technical note, the outcome was never dementia itself, but a dementia diagnosis in an administrative record. Whether a case is captured depends on who comes through the doctor’s door and how a clinician codes them. The eligibility moment is also a healthcare-contact moment, so anything that nudges how often the just-eligible are seen and worked up (e.g., by getting shingles) can shift recorded dementia without changing the real rate. It is also why the same design can give different answers in different health systems, which is precisely what happened next.

What a new analysis shows

My friend, the venerable George Davey Smith and colleagues did the next obvious thing and ran the identical design in a far larger population, which was presented at a guest lecture on June 17th. England used the same vaccine, the same date, the same cut-off, so an almost identical natural experiment exists, across 6.3 million people (roughly twenty times the Welsh sample).

As one would expect from this group, the study is persuasive. First they confirmed that eligibility produced a clear drop in recorded shingles. This is proof the design works (and the vaccine, which is excellent, does its actual job). Then they looked at dementia, and found….nothing.

A complete null result, stable across sensitivity analyses, with no bias they could find to explain the gap with Wales.

This does not quite close the question completely, as no single study ever does. England codes dementia from hospital records, which capture it less completely than Welsh primary care, so a defender could argue the effect is simply being missed. This criticism is weak however, because the same design plainly can detect the vaccine's effect on shingles in these very people. In addition, restricting the Welsh analysis only to hospital data (like the new English analysis) doesn’t alter their findings, showing it should be robust whichever of these types of data you use.

Speaking to the differences in these findings, a point made in the lecture was that the type of method deployed to these study (regression discontinuity design, for those who are interested), enables the researcher a huge degree of freedom in making analytical decisions. Each of these can potentially drastically alter the ultimate result.

Ultimately, the failure to observe an effect size so large it should be visible from space, in the largest and most robust replication study to date, is devastating evidence against this hypothesis.

Suddenly, a trial is urgent?

Within days of the null replication, a Nature Medicine commentary argued that large randomised trials of the live vaccine for dementia are urgently needed, and that we have never had a more robust body of observational evidence for any dementia intervention. Notably, its author is the researcher behind the Welsh, Australian and Canadian observational data.

He is right that a trial would ultimately be the only way to provide a definitive answer, that observational evidence has gross limitations, and may be right that the live vaccine is the one to test. But the framing is exactly what this episode should teach us to distrust. "The most robust observational evidence we have ever had for a dementia intervention" is, to be blunt, an extremely low bar: that field is a graveyard of observational findings (HRT, vitamin E, ginkgo, B vitamins) that looked wonderful until someone ran the trial. Let’s also be aware that three of the four headline experiments come from one group running one design, while the single genuinely independent large-scale replication is the one that found nothing.

As is happens, such a clinical trial is already underway in Denmark; but with the new, recombinant vaccine, not the live-attenuated vaccine to which all this evidence refers. Recruitment is underway and over 100,000 people will be needed to assess if the vaccine reduces cardiovascular complications or dementia over a 3y period.

This trial is possible in Denmark as no shingles vaccine is currently offered on the national schedule there, unlike in the US or the UK.

This raises an important point - it’s not clear who the control group would be if a study of the old, live-attenuated vaccine was to be done in the US (as I understand the NIH are considering). If the control arm receives the current, recombinant vaccine (which they are entitled to), and this also prevents dementia (which hopefully we’ll discover from the Danish study), the trial would show no difference between the two even though they both prevent dementia.

This leaves me to ask, can we ethically randomise patients to not receive a vaccine which we already know is highly effective at the thing it is actually supposed to do: protecting against shingles? I am aggressively pro-clinical trials, and even I find this idea questionable. The commentary completely avoids referencing the control group at any point.

In my opinion, much more evidence from different streams of data (such as mechanistic work) are required to justify such an endeavour.

In aforementioned lecture, George Davey Smith speaks to the importance of triangulation of evidence; not relying on a single source or method of research, but collating multiple different types of observational and experimental evidence to try and establish causality. Even for associations as strong as smoking and lung cancer, such triangulation was necessary to eventually convince the scientific community of the relationship (this was a major source of disagreement between the two titans of medical statistics and epidemiology of the 20th century, Ronald Fisher and Austin Bradford Hill).

The part that worries me

The messaging about these studies from the people we trust to communicate science has completely missed the mark.

From very early on, the finding that shingles vaccines prevent dementia was being relayed to the public as established fact. One prominent, widely trusted, emphatically pro-science communicator told a national audience that the shingles vaccine reduces Alzheimer's and dementia "by at least 20 to 25 percent", not as a hypothesis but as something we had simply learned, folded into advice on how to age well.

The finding was exciting, and it flattered a “pro-vaccine” worldview, so scepticism got switched off. When people who are fervently anti-vaccine overstate a harm we rightly demand rigour and replication; when a result flatters the pro-vaccine side, the same people wave it through. It is the identical error, and when an oversold finding wobbles, the people who never trusted the messaging get to say, accurately, that scientists hyped a vaccine benefit that did not hold up. More of public health's credibility, which is hard won, is lost.

I am dismayed at how “Sci-Com” keeps losing its way, and how often the biggest names are guilty. The job is not simply to parrot a studies findings but to rigorously interrogate them: what was the design, how big was the effect, does it replicate, what would have to be true for it to be wrong? Reposting a conclusion with an admiring adjective is not communicating science; it is laundering a press release. At this point you’re playing the role of a publicist, not a scientist.

That appraisal, slow and unglamorous and sometimes deflating, is the whole value we are meant to add as science communicators.

Summary

The initial hype over an enormous risk reduction in dementia from receiving the shingles vaccine has not held up in the largest independent replication study to date. The hypothesis is not dead (although it is on life support), but it’s hard to see how a trial is currently the answer. The lesson is not that the vaccine is useless, nor that natural experiments are bad, but that an unbelievable result deserves the same hard scrutiny whether or not it tells us what we hoped to hear. Science Communicators must give due effort to appraising the research that they cite, not simply repeating the headlines. At present it is not good enough.

So the truth: does the shingles vaccine prevent dementia? Probably not - although I would love it to be proven so.

Two trials reported in the last few weeks, in two completely different infections, point at the same uncomfortable idea. Some of the things we do for our sickest patients, that the guidelines tell us to do, and the observational evidence seemed to support, may have been harming, or even killing them.

Both of these findings are preliminary and not published in full. Findings from the REMAP-CAP trial have been presented at the CCRUK conference and the SNAP trial (adjunctive clindamycin arm) at ESCMID. But the direction they point is important, because the lesson is bigger than either drug.

Oseltamivir in critically ill influenza (REMAP-CAP)

REMAP-CAP is a large, multi-centre randomised trial for influenza and other respiratory infections (I am the lead paediatric investigator for my hospital). In the relevant part of the study, patients are randomised to 5 days of the antiviral medication oseltamivir (Tamiflu), 10 days, or no antiviral. This part of the study was recently paused after an interim analysis, usually indicating either a safety issue or that the drug could not reach the pre-defined superiority threshold.

The results have now been presented for those aged 12 years and older in the ICU - the sickest patients. In this group, 90-day mortality was higher in those who received Oseltamivir; roughly 19% for those randomised to 5 days and 22% to 10 days, against 14% with no antiviral. The adjusted odds ratios were around 2.3 in both treatment arms. The study was analysed using Bayesian methods, with a posterior probability of harm (increased mortality) at over 96%.

The trial team have since released an “information for healthcare professionals”Q&A with extra details, such as subgroups who seemed particualry high risk; those with shock, bacterial superinfection, symptoms for >5d, and the immunocompromised. They have explicitly recommends the drug not be prescribed for critically ill patients aged 12 and older with influenza.

I would like to re-emphasise that this is not a subtle signal. Oseltamivir is recommended for severe influenza by essentially every major guideline, and the evidence underpinning that recommendation has always been observational, and questionable. The most influential piece was the PRIDE collaboration’s individual-patient meta-analysis (Muthuri and colleagues, Lancet Respiratory Medicine, 2014), which pooled some 29,000 patients hospitalised with H1N1pdm09 across 38 countries and reported a 19% reduction in mortality with neuraminidase inhibitors overall, and 25% in adults. This was even larger still if the drug was started early. This looked compelling, and it shaped a decade of practice.

Unfortunately, we know that this is exactly the kind of data that flatters a drug given to the people most likely to recover anyway. The patients who get oseltamivir early are, on average, the ones who present sooner, are looked after more attentively, and are less moribund. One group re-analysed similar British H1N1 data accounting for immortal time bias (taking into account the fact that you have to survive long enough to be given the drug) and the apparent benefit evaporated (hazard ratio 1.03, 95% CI 0.64–1.65). That was an important warning, but REMAP-CAP has now randomised the question properly, and the answer points the other way.

Adjunctive clindamycin in Staph aureus bacteraemia (SNAP)

The case for adjunctive clindamycin (giving it alongside the primary antibiotics to treat infections with the bacteria Staphylococcus aureus) is compelling. Clindamycin’s mechanism of action is to inhibit protein synthesis (stop it making proteins), therefore it should switch off the toxins that drive much of the damage in severe infections. Observational research seemed to bear this out. A review of 92 cases of staphylococcal necrotising pneumonia found that regimens including an antitoxin agent were associated with lower mortality (P = 0.007), with supporting case series in PVL-positive invasive infection and severe skin and soft-tissue disease. The same logic has also long been applied to invasive Group A Strep. It is an entirely reasonable thing to have believed.

The SNAP clinical trial (for which I sit on the Global Trial Steering Committee) asked whether it actually helps in Staphylococcus aureus bloodstream infection. In this arm of the study, patients were randomised to receive 5 days Clindamycin in addition to their first line antibiotic, or not receive any adjunctive treatment. Across nearly 3,800 patients, 90-day mortality was 16.9% with clindamycin versus 15.2% without (adjusted OR 1.15), and the trial declared the intervention futile with very high probability.

But it gets worse. In the ICU subgroup, who are the sickest patients for whom the toxin argument is most seductive, mortality was 30.4% with clindamycin against 24.7% without (adjusted OR 1.47). This leaves a posterior probability >90% of increased mortality. More diarrhoea, no benefit, and a worrying signal of increased mortality precisely where we were most tempted to reach for it.

The pattern

In both cases the instinct is the same, and is completely natural:

Give an antiviral. Add a second antibiotic. The mechanism makes sense, the observational data point the right way, and doing less feels uncomfortable for physicians.

But the observational data point the right way because of who receives these drugs, not because of what the drugs do. The only way to separate the two is to randomise. When we finally do, the answer is sometimes that the thing we were sure would help does nothing, or in this case, possibly worse.

We must always remember that “do everything”, without sufficient evidence, carries a high risk of doing something that actively harms the patient

This now leaves us in an awkward position. Until the full papers are published and digested, many guidelines still say to use these drugs, and we now have good reason to believe that in some patients they may do real harm1. The clinician Q&A for REMAP-CAP states that these findings don’t apply to other populations, such as children <12 years; but what are my team supposed to advise when 10 or 11 year olds are admitted to PICU with flu this winter?

This is a firm reminder that “we must do more for the sickest” is a human reflex, not an evidence base. The discipline of waiting for a trial, rather than acting on what feels right, is the thing that actually protects patients.

More to follow when both papers are out in full.

If you’ve been a subscriber for a while, you’ll have noticed that for a long time the newsletter was quieter than it should have been. The truth is that clinical and academic work absorbed the time I used to spend writing, and the gaps got longer until momentum was lost. I have missed it!

I would like to avoid that happening again, so here’s what I’m changing.

What this newsletter is for

For anyone who’s joined recently, or who’s forgotten why they signed up: The Munro Report exists to write clearly about paediatric infectious diseases, child health, and the quality of evidence behind both. The audience has always been mixed; parents who want to understand what’s actually happening when their child is unwell, clinicians who want a careful read of new data, academics who want commentary that takes methodology seriously, and journalists or policy people who want to know what the evidence actually shows.

I try to do one thing reliably: explain what we know, what we don’t, and how confident we should be about the difference. That hasn’t changed. What’s changed is how seriously I’m going to treat the work of doing it.

What’s changing

Three things.

Posting will be more regular: My aim is to publish every few weeks, with a working mix of evidence-quality commentary, outbreak news, and parent-facing pieces on the everyday child health questions that come up again and again.

The visual identity is being refreshed: Header images, the publication mark, and the overall look are being brought into a coherent theme that matches what the writing aspires to; a serious editorial publication. You may have noticed some of this already, and it will continue rolling out over the coming weeks.

A paid tier is opening: Almost everything on The Munro Report will remain free, as it always has been. Outbreak commentary, evidence reviews, and parent-facing pieces will all remain free, on publication, to anyone who subscribes. I will offer some additional material for those who offer support through a paid subscription by way of thankyou, but the substantive work stays open to everyone.

The reason for opening paid at all is editorial independence. A newsletter funded by readers doesn’t need sponsors, advertisements, or institutional patronage that comes with strings attached. And it lets the writing be sustained at a level the spare-time-around-clinical-work model has otherwise struggled to manage.

If the newsletter has been useful to you and you can spare it, a paid subscription is how you make more of it possible. If you can’t, or you’d rather not, that’s entirely fine. You remain a welcome reader, and the work you came for stays free.

That’s the reset. The next post will be along shortly.

Thank you for joining me.

The news from central Africa over the past two weeks has been grim, and it is getting worse. On 15th May, the Democratic Republic of the Congo and Uganda jointly declared an outbreak of Ebola disease, and two days later the WHO declared it a public health emergency of international concern. It is the DRC’s 17th Ebola outbreak since the virus was first identified in 1976, and it has escalated with alarming speed. The background to the current outbreak was covered here previously.

The Munro Report

Not now, Ebola

As if the ongoing hantavirus cluster on a cruise ship were not enough, the world now has another viral haemorrhagic fever to contend with. On May 15th 2026, Africa CDC confirmed an outbreak of Ebola virus disease in Ituri province, northeastern Democratic Republic of the Congo (DRC). Less than 48 hours later it was declared a…

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3 months ago · 27 likes · Alasdair Munro

Here is an update on the current situation, why it is so terrible, and why this is not the beginning of a global pandemic.

The situation

The numbers are bad and moving daily. As of June 1st, the DRC and Uganda Ministries of Health report 321 confirmed cases in the DRC, including 48 confirmed deaths, with a further 116 suspected cases still under investigation. The great majority are in Ituri Province, where the outbreak began, but it has spread west into North and South Kivu. Uganda has 11 confirmed cases, including one death, several linked to travel from the DRC; cases have reached the capital, Kampala.

Two features make this particularly difficult. The first is that by the time the outbreak was formally declared, it already had hundreds of suspected cases. It’s like a fire that had been spreading for some time before anyone reached for the alarm.

The second is community resistance to the response. This is a recurring and tragic feature of Ebola outbreaks. There are a mix of reasons with related results.

Families, understandably, do not want their sick relatives taken away to isolation units from which many never return, and traditional burial practices involve washing and touching the body of the deceased. There have been reports of family members retrieving bodies from quarantine. This is an act of love that, with this disease, is one of the most dangerous things a person can do. It is a particular tragedy of Ebola that the people most likely to catch the disease are those caring for others who are dying of it; both as family members or healthcare workers.

Misinformation is rife, including conspiracy theories around organ harvesting, the government scamming for aid money, or even that the Ebola virus does not exist at all. Locals set fire to the Ebola quarantine unit at Rwampara General Hospital, with many patients escaping.

As if this is not difficult enough, much of the affected area is currently embroiled in a civil war. Conditions are almost unimaginably difficult for frontline workers providing aid and healthcare. Resistance to outbreak response was a defining problem of the West African epidemic a decade ago, and it is the reason community engagement matters as much as any medical intervention.

A quick warning on some of the graphs you may be seeing shared, including by serious commentators (or even frustratingly by the BMJ). Some charts circulating online show case numbers rising near-vertically over the past fortnight, which looks terrifying. But much of that rise reflects case ascertainment catching up with an outbreak that was already large, not the speed of new transmission. When an outbreak is declared late, the early part of any cumulative curve always looks explosive, because you are counting cases that accumulated over weeks and recording them all at once.

Tellingly, the DRC's figures were recently revised downward after authorities removed non-cases and reclassified others. The curve was partly an artefact of counting, not just of spread. The outbreak is serious enough without misreading the shape of the graph, and this only risks further mistrust in health communicators.

Why this is not the next pandemic

Ebola, for all its horror, is not suited to becoming a pandemic. The pathogens that cause pandemics share a particular profile: they transmit efficiently through the air, and crucially, they transmit before the infected person feels very unwell. That combination is what allows a virus to spread silently through a population faster than any response can contain it. It is what made Covid-19 impossible to contain.

Ebola is almost the opposite. It is not airborne. It spreads through direct contact with the bodily fluids of someone who is symptomatic, and people with Ebola become very symptomatic, very obviously, very quickly. Transmission is concentrated in the late symptomatic phase and, grimly, around death, which is why infections cluster so tightly around carers, healthcare workers, and funerals. A disease that mostly spreads from people who are visibly, severely ill is a disease you can, in principle, contain by isolating the ill and managing burials safely. This is hard, dangerous, resource-intensive work, but containable in a way that an airborne, pre-symptomatic virus simply is not.

This also means that the interventions people instinctively reach for after the last pandemic are largely beside the point. Community masking will not help here. The transmission route is wrong. This is a disease controlled by contact tracing, safe isolation, safe burial, and hopefully, vaccination.

It also makes some of the political responses hard to fathom. The US has declared it "cannot and will not allow" any Ebola cases onto American soil, and rather than repatriating exposed citizens (as it did during the 2014–16 West African outbreak) it has moved to house them in a quarantine facility at an air base in Kenya, a country with no Ebola cases of its own. The plan has been temporarily blocked by the Kenyan High Court pending a legal challenge from local civil society groups, who object to having infectious disease risk "externalised" onto Kenyan territory. Leaving aside the question of a government declining to bring its own citizens home, the epidemiology does not warrant this response. With a disease this hard to catch from someone who isn't visibly ill, sealing borders does little except discourage the transparency and cooperation that outbreak response depends on. Indeed, it makes it more likely that high risk individuals will seek to circumvent the very safety nets that are put in place to prevent imported cases. Some lessons are never learnt.

The vaccine story

Amongst all the very bad news about this outbreak, there is a cause for some optimism.

We already have a highly effective Ebola vaccine but for the wrong species. The rVSV-ZEBOV vaccine (Ervebo) was tested in the remarkable “Ebola ça Suffit” ring vaccination trial in Guinea in 2015, which used a design inspired by the strategy that eradicated smallpox: when a case is confirmed, you vaccinate their contacts and their contacts’ contacts; the “ring” around the case. The interim results showed 100% efficacy against Ebola disease from ten days after vaccination. It was a landmark, and ring vaccination has been a mainstay of outbreak response ever since.

The complication is that Ervebo protects against Zaire Ebolavirus. This outbreak is caused by Bundibugyo virus, a different species, and we do not have an off-the-shelf licensed vaccine for it.

What we do have is a platform. The Oxford Vaccine Group is producing a vaccine, ChAdOx1 BDBV, built on the same ChAdOx viral-vector technology that underpinned the Oxford/AstraZeneca Covid vaccine. It is currently in preclinical testing (the animal studies needed before it can be given to people) with manufacturing already running in parallel through Oxford and the Serum Institute of India.

I find this particularly encouraging, as I was involved in the deployment of the Covid vaccine. I can tell you from my own experience, that the speed at which a platform like this can move from genetic sequence to deliverable doses, when the will and infrastructure are there is astonishing. The ChAdOx platform was built precisely for this purpose. Swap in the genetic code for a new pathogen’s surface protein, and much of the manufacturing and safety groundwork is already done.

CEPI have now encouragingly added their backing to the project, alongside two other candidate vaccines for Bundibugyo virus; these include an mRNA vaccine, and a rVSV based vaccine (this is the same platform that the successful Zaire vaccine was built on). Separately, GAVI have also offered tens of millions of dollars in purchasing commitments to ensure vaccine makers know there will be a market if the vaccines are effective.

The “Ebola ça Suffit” trial gives us a proven model for testing a vaccine’s efficacy in the field, in the middle of a real outbreak. The pieces exist. The question is whether they can be assembled fast enough to matter for this outbreak, rather than the next one.

There are also plans in the work for rapid deployment of clinical trials for antiviral therapies, including monoclonal antibodies and the antiviral medicine “Remdesivir”, used during the Covid-19 pandemic. Finally, a post-exposure prophylactic antiviral, “Obeldesevir” (yes, this is related to Remdesivir), is also planned to enter trials in the region

These are predominantly aimed at treating patients who have contracted Ebola, or already been exposed but will not be impactful for stemming the spread of disease. This is why vaccination is key.

Undertaking these trials in a literal warzone alongside a population with high degrees of institutional mistrust will be a challenge, to say the least. Whilst they will come quickly, they won’t come quickly enough that they can be depended upon. Boots-on-the-ground public health measures are needed to stem the tide for the foreseeable future.

Summary

This is a serious and escalating outbreak, made worse by late detection and by community resistance to the response. These are the same human factors that have always made Ebola so hard to fight.

This is not the beginning of a pandemic. Ebola is not airborne, it spreads overwhelmingly from people who are visibly and severely ill, and it is therefore containable through isolation, safe burial, and ring vaccination. We have a proven vaccine for the wrong species and promising candidates for the right one in early development. The danger here is real and local; the risk to the wider world is low. Both things are true at once.

Adam Kucharski recently posted a thoughtful piece reviewing Helen Pearson’s new book Beyond Belief, in which he picks up her concept of “aluminium-standard” evidence. This describes evidence which is faster, cheaper, and often more feasible than the gold standard, but still good enough to inform the decision being made. The argument is that demanding gold-standard evidence before action can become a form of “weaponised certainty”; a way for people opposed to an intervention to keep raising the bar of evidence until no decision is possible.

Understanding the unseen

Do we need more 'aluminium-standard' evidence?

In 1971, a doctor named Archie Cochrane showed a group of cardiologists the results of a clinical trial he had been running. The response was furious: ‘Archie, we always thought you were unethical. You must stop this trial at once…

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4 months ago · 74 likes · 9 comments · Adam Kucharski

This is true, but it left me considering another problem. If gold-standard evidence isn’t always available, and isn’t always required, how do you know when the evidence you have is enough? There is a different problem where “Aluminium-standard” risks becoming weaponised in its own right, or a way of saying “whatever evidence I happen to find convincing, applied to whichever decision I happen to want to make.” We need a way of knowing when good enough really is good enough.

I want to offer a framework for thinking about this that is rarely articulated in public-facing evidence debates, and I think makes the argument easier to navigate.

Belief is not binary

The first thing to get out of the way is the idea that knowledge is something we either have or we don’t. We essentially never know anything. We hold beliefs with varying degrees of confidence, and evidence is what moves those beliefs.

This probability language used for this is known as Bayesian (after the Reverend Thomas Bayes), but it is intuitive and it does not require any formal training in probability to use. We are all doing it constantly.

You have a prior belief, for example about whether your child is unwell (”she seems off today”), you gather evidence (she has a temperature, she won’t eat, she’s unsettled), and you update your belief accordingly. By the time you decide whether to call the GP, your confidence has moved from thinking “she might have something”, to, “she probably has something”.

Three things matter for any decision of this kind. Your prior belief: how likely the thing was before you had this evidence. The strength of the evidence itself: how much it should move that belief. And the key, often overlooked element - the threshold for action: how confident you need to be before doing whatever it is you are considering doing.

That gap is what the evidence has to close.

Why medicine usually demands more

Medicine has earned its reputation for high evidentiary standards, and rightly so. Kucharski wisely refers to the story of Archie Cochrane and his attempts to overcome “eminence based medicine” with practice based on high quality evidence.

For most novel interventions, the prior is uninformative. We have a mechanistic hypothesis, e.g., this drug should bind that receptor and produce that effect, but mechanism has a long and humiliating history of failing to predict clinical outcome. The graveyard of plausible-sounding interventions that turned out not to work, or to actively harm patients, is enormous.

This is partially a reflection of the fact that humans, including those of us trained in medicine, systematically overestimate the benefits of interventions and underestimate their harms. Plausible mechanisms feel like evidence. Anecdotal successes are remembered; failures are attributed to the disease. This is true of clinicians, of patients, of researchers, and of policymakers.

Meanwhile, the threshold to act is high. Most medical interventions are expensive, and recommended to large numbers of people, many of whom are otherwise well, would have recovered anyway, or had other options available. The downside of recommending the wrong thing is borne by people who did not choose to take on the uncertainty. This is important because an individual choosing to try an experimental treatment for their own incurable illness can apply one threshold; a public health body recommending an intervention to millions applies a much higher one.

Another crucial element is that in medicine (or even public health) we usually can run the trial, and generate the “gold standard”. Unlike Kucharski’s caribou where the breeding programme cannot meaningfully be randomised, most drug interventions, vaccines, devices and procedures can be tested in proper clinical trials. In fact, many things you might imagine to be impossible to randomise could be, if scientists are able to think more flexibly. The feasibility of generating better evidence raises the bar on whether you should act on worse evidence.

When the gold standard is genuinely unavailable, aluminium becomes a defensible substitute. When the gold standard is available but slow, it’s more complicated.

When the threshold legitimately moves

The framework also explains why we sometimes accept lower-quality evidence in medicine and are right to do so.

Severe outcomes raise the cost of inaction, which lowers the threshold to act. Limited alternatives narrow the comparison: when there is no other plausible option, you are no longer asking “is this better than nothing” against a high bar, but against a much lower one. Rare diseases change feasibility: a trial that would resolve uncertainty cannot practically be run, so the alternative to acting on imperfect evidence is acting on no evidence at all. Established safety profiles reduce the potential costs of lowering the threshold.

Each of these is a specific lever being pulled, not a general permission to be more relaxed. That distinction is what separates exceptions with good reasons from special pleading.

Masks

Few topics have been argued more poorly than masks during the COVID-19 pandemic. People saying “we know masks do/don’t work” was worse than unhelpful, because almost everyone involved was using the word “masks”, AND the word “work”, to mean different things, and was applying their conclusion to different decisions and different thresholds.

Consider a fit-tested N95/FFP3 worn by a healthcare worker entering a respiratory isolation room. The prior is informative and favourable: regulators have tested these devices extensively, the mechanism by which they work is well understood, and we are confident they remove most particulate matter under fixed conditions. The threshold to act is low: the intervention is brief, the cost to the wearer is minimal, the contact is high-risk, and the alternative is exposure. Even a thin RCT evidence base does not need to do much work to clear that gap. Recommending this is straightforward.

Now consider intermittent community mask use. Cloth or surgical masks, worn variably, removed during the periods of highest transmission risk (at home, eating, socialising with close contacts). The prior is much weaker, because most of the mechanistic confidence applies to a different intervention under different conditions. The evidence is weak: the RCTs that exist are inconclusive, and observational evidence that is heavily confounded and (depending on who generated the study) often produces effect sizes so large they are implausible at face value. The threshold to act depends on what you are deciding to do.

If the decision is whether to recommend mask use to the public, the threshold is much lower. The intervention is relatively cheap, the imposition is small for most people, and a recommendation merely shifts the choice for people who would not have considered it otherwise. Even weak evidence could feasibly clear that bar.

If the decision is whether to mandate mask use across entire populations for years at a time, the threshold is much higher. Mandates impose real social, educational, economic and environmental costs, and risks damage to public trust in institutions. The evidence required to justify a mandate is therefore substantially more than the evidence required to justify a recommendation, even though the intervention itself is nominally the same.

I think this helps some of the mask debate become intelligible:

Libertarians will have vastly different evidence thresholds to socialists on public health interventions. This isn’t right or wrong in any testable or scientific sense. I think many people are just resistant to admitting it.

Which failure mode has cost us more?

It is absolutely right that weaponised certainty exists and is dangerous. Opponents of an intervention have clearly raised the evidentiary bar as a way of blocking action. Climate change is a current example and vaccine debates often have the same shape. Demanding perfect evidence for things you already oppose, and accepting anecdote for things you already support is dangerous and intellectually dishonest.

Within the realm of medicine and public health however, I think the inverse of this has been more consequential. Call it weaponised urgency: invoking the impossibility of perfect evidence to bypass evidence the field actually could have generated. “We cannot wait for an RCT” when the RCT could have been run in a few months but never was. “Action is needed now” when the burden of disease will still be there in a year, and a year is what would have produced a defensible answer. The pandemic offered repeated examples.

The reason this matters is that despite the efforts of people like Archie Cochrane and Austin Bradford-Hill, medicine’s track record is littered with interventions adopted on insufficient evidence and later withdrawn; not with interventions withheld until certainty arrived and never came.

The textbook examples include hormone replacement therapy being recommended for cardiovascular prevention in healthy postmenopausal women on the strength of observational data, until the Women’s Health Initiative trial showed it caused more harm than benefit. Class I antiarrhythmic drugs were given routinely to patients after heart attacks on the mechanistically obvious basis that suppressing arrhythmias should save lives, until the CAST trial found they tripled mortality. The list is long, the harms in each case were substantial, and in every instance the evidence to know better was either available, or could have been generated, before the intervention was rolled out.

Weaponised certainty is absolutely real, and is a problem, but it is rarely the move that ends up doing the most damage in medicine. The more common pattern is acting too fast, on optimistic priors, with evidence that turns out not to support the confidence we placed in it.

What the framework can and can’t do

Where two people work from the same evidence and reach different decisions, the disagreement is usually about the threshold, not the evidence. This framework helps us see that, but it does not tell you which threshold is right - or if there truly is a “right”. We must avoid mistakes such as claiming that evidence is insufficient when your real objection is to the threshold.

There may be some exceptions where waiting is itself a decision with costs, and those cases need to be argued explicitly. But the prior on “we should act now on what we have” deserves to be more sceptical because historically that is the more common mistake we have made.

Aluminium standard evidence is not lower-quality gold-standard evidence. It is what you reach for when the gold standard is not available, and only when the gap you are trying to close is small enough that aluminium can do the work. The art of evidence based decision making lies in being able to tell the difference. The art of evidence based public debate lies in being able to say, explicitly, which one you think you are doing.

Work out whether you are arguing about the evidence (science) or about the threshold (values) before you dive in.

As if the ongoing hantavirus cluster on a cruise ship were not enough, the world now has another viral haemorrhagic fever to contend with. On May 15th 2026, Africa CDC confirmed an outbreak of Ebola virus disease in Ituri province, northeastern Democratic Republic of the Congo (DRC). Less than 48 hours later it was declared a public health emergency of international concern (PHEIC), the highest level of public health threat. At the time of writing, over 300 suspected cases and at least 88 deaths have been reported, with sequencing confirming the Bundibugyo strain.

This is the DRC’s 17th recorded Ebola outbreak since 1976. And it comes with a particular complication: there is no approved vaccine or treatment for this strain of the virus.

This outbreak already looks to be highly problematic.

What is Ebola?

Ebola virus disease causes viral haemorrhagic fever (VHF), one of the most severe clinical syndromes in infectious disease. The, “Haemorrhagic” is so-called as these illnesses cause damage to blood vessels and the clotting system, leading to bleeding, organ failure, and a very high risk of death. Unlike Hantavirus, it belongs to the family of High Consequence Infectious Diseases (HCID), deemed so for their high mortality, lack of treatments, difficulty to detect and potential for spreading in the community.

Ebola is both interesting and terrifying. It belongs to the family Filoviridae -- filoviruses, from the Latin for thread. Under an electron microscope it is one of the longest viruses known, forming distinctive elongated filaments sometimes shaped like a shepherd’s crook or the number 6. It looks nothing like how we imagine most viruses.

The virus was identified in 1976 following simultaneous outbreaks in Sudan and in what is now the DRC. The Congolese outbreak occurred in Yambuku, a remote village near the Ebola River. The name is, by the discoverers’ own account, wrong: they wanted to avoid stigmatising Yambuku and chose a nearby river as a more neutral reference, but subsequently found it was not actually the closest river to the outbreak site. The name stuck anyway.

Four species cause disease in humans: Zaire, Sudan, Bundibugyo, and Tai Forest, and they are all quite different. Zaire is the most feared, with an untreated case fatality rate (CFR) around 79%, it is responsible for the largest and deadliest outbreaks on record. Sudan carries a CFR of around 54%. Bundibugyo, identified for the first time in Uganda in 2007, has a CFR closer to 32% - the fact this makes it the “mild” Ebola is a depressing thought.

One additional species worth mentioning is Reston virus. It infected laboratory workers in Virginia in 1989 who developed antibodies but never got sick. The alarming thing about Reston is that spreads through the air between monkeys (airborne Ebola…). Thankfully it doesn’t cause disease in humans.

The natural reservoir is fruit bats, which appear to catch the virus without becoming ill. The 2014 West Africa outbreak was traced to a two-year-old boy in Guinea who had likely played near a hollow tree colonised by bats. The virus transmits between humans through direct contact with bodily fluids of infected individuals. Ebola is not airborne in the conventional sense.

The virus does other weird things, such as persist in immune-privileged sites like the eyes, testes, and central nervous system, long after a person has clinically recovered. Cases of sexual transmission from male survivors have occurred more than a year after recovery. A Scottish nurse even developed Ebola meningitis nine months after being discharged. This persistence in survivors is one reason response efforts cannot just stop when a patient leaves hospital.

In central Africa, funerals are a major driver of spread. Traditional washing and preparation of bodies, combined with extremely high viral loads in the deceased have made funeral practices a repeated amplifier in nearly every outbreak. Safe and dignified burial programmes are now a core pillar of the response.

Despite all this, most of the world paid little attention to it for the first three decades after its discovery. Ebola killed roughly 1,500 people in total across small, geographically isolated events, contained through case isolation and contact tracing. The disease was seen as too rare and too remote to justify pharmaceutical investment, and vaccine development stalled.

Then came 2014.

What 2014 changed

The West Africa outbreak of 2014 to 2016 infected more than 28,000 people across Guinea, Liberia, and Sierra Leone, and killed over 11,000. It grew in urban centres with weak health systems, overwhelmed the response capacity of three countries, and spread internationally, including infections of healthcare workers in Spain and the United States. By any measure, it was catastrophic.

It was also the event that finally triggered the development of effective countermeasures. Two vaccines are now licensed: rVSV-ZEBOV (Ervebo) and the two-dose Ad26.ZEBOV/MVA-BN-Filo regimen, and a monoclonal antibody combination (Inmazeb) has substantially reduced mortality (in clinical trials at least). Crucially, modern supportive care has significantly improved outcomes even without specific antivirals. Many historical “Ebola deaths” were really deaths from dehydration and electrolyte derangement that intensive care can correct. With supportive care and monoclonal antibodies, Zaire-strain mortality has been brought below 35% in trials.

All of which is good news. Except every approved countermeasure targets the Zaire strain.

The current outbreak

The outbreak is centred on Ituri province, in the remote northeast of the DRC. Ituri sits over 1,000km from Kinshasa, borders both Uganda and South Sudan, and is currently experiencing active conflict between rival militia groups. A healthcare worker was the first known case, with symptom onset on 24th April with fever, bleeding, vomiting, and severe weakness, and subsequently died at a medical centre in Bunia, Ituri’s capital. WHO was alerted to an unknown illness causing high mortality in Mongbwalu health zone on 5th May, including the deaths of four healthcare workers within four days of each other. The outbreak was officially declared on 15 May. On 17th May, WHO declared it a PHEIC.

An important detail from the early outbreak has emerged. Initial samples tested negative for Ebola. The available rapid tests detected only Zaire ebolavirus, not Bundibugyo, and a positive Bundibugyo result was not confirmed until 14th May - nearly six weeks after symptom onset in the index case, three weeks after the first cluster of healthcare worker deaths. There is speculation that the detection delay may be linked to recent cuts to global health programmes. That speculation will need to be assessed properly in due course, but the basic point is that the tools deployed to detect the outbreak could not detect the strain causing it.

It was caught late, and it was caught late for a specific reason.

The case counts reflect this delay. As of 18 May, DRC has reported 10 confirmed cases, 336 suspected cases, and 88 deaths, across at least nine health zones in Ituri. A separately confirmed case has been reported in Kinshasa (in someone returning from Ituri), and another in Goma, a city in North Kivu currently under the control of the March 23 Movement, which adds a substantial complication to contact tracing and response efforts.

Concerningly, Uganda has confirmed two cases in Kampala, with one death, in individuals who arrived from DRC within 24 hours of each other and have no apparent link, suggesting more than one importation chain. An American healthcare worker who had been caring for patients in the DRC tested positive on 17th May and is being moved to Germany for treatment. The US has implemented enhanced travel screening and entry restrictions for travellers from DRC, Uganda, and South Sudan.

The geography compounds everything. Mongbwalu is a high-traffic mining town, and the working hypothesis is that the outbreak originated there before patients moved to Rwampara and Bunia seeking medical care. Ituri has over 270,000 internally displaced people and 1.9 million people identified as being in humanitarian need. The combination of high population mobility, active conflict disrupting health infrastructure, an urban hotspot, an outbreak straddling territory controlled by different armed groups, and the geographical proximity to Uganda and South Sudan creates the conditions under which small outbreaks readily become large ones. WHO has been explicit that the true scale of the outbreak is likely larger than the reported figures, on the basis of the high positivity rate in initial sequencing (eight positives in 13 samples), the unusual clusters of community deaths being reported across multiple health zones, and the rising trend in syndromic surveillance.

The current situation is bad, and is likely to look worse as more information becomes available.

Worth noting in the middle of all this: Jean-Jacques Muyembe, the Congolese virologist who co-discovered Ebola in 1976 as a young doctor drawing blood samples in Yambuku, now heads the DRC’s National Institute for Biomedical Research and is on the response. The man who helped identify the virus is leading the response to it fifty years later, in the same country. It is one of the more remarkable careers in modern infectious disease.

Why this one is harder

The current outbreak is Bundibugyo, not Zaire. Global vaccine stockpiles exist for Ebola, but the vaccines in it were not designed to protect against this strain. There are no approved treatments. Africa CDC has convened an urgent coordination meeting with health authorities from DRC, Uganda, and South Sudan alongside pharmaceutical companies including Merck, Gilead, Regeneron, and Moderna, plus CEPI and Gavi, to assess what options exist. CEPI has indicated it can support accelerated trial facilitation if required. For now, the response depends on the classical pillars: case isolation, contact tracing, safe and dignified burials, and community engagement.

The lower CFR of Bundibugyo (32% vs Zaire’s 79%) is a silver lining (if you can call it that). If a third of confirmed cases die rather than four-fifths, the clinical picture looks different. This may add to the explanation of why the outbreak grew so large before being detected, if early cases were attributed to other causes. However, it certainly does not make this a minor outbreak.

The mode of transmission of Ebola means this is extremely unlikely to become a serious, sustained transmission risk in Western countries. Even during the 2014 outbreak, the UK only saw three cases which were all in healthcare workers looking after patients with Ebola. However, frontline staff around the world will once again be on high alert for gastrointestinal symptoms in travellers returning from central Africa.

Despite the fact this outbreak already significantly more deadly than the cruise-ship Hantavirus outbreak, it is likely receive receive a fraction of the media attention - unless cases end up on our doorstep.

Summary

Ebola is a filovirus which causes devastating viral haemorrhagic fever, and Bundibugyo is one of four species pathogenic to humans - less lethal than Zaire but still very serious. It was under-researched until the 2014 to 2016 West Africa outbreak finally drove the development of effective vaccines and treatments, but those tools are specific to Zaire. The current DRC outbreak involves Bundibugyo, was detected late, sits in a conflict-affected region with high cross-border mobility, and has already spread to Uganda. The response is now reliant on the same set of public health interventions that were available in 1976. Since Ebola spreads through close contact with bodily fluids and has never sustained transmission outside Africa, the risk to Europe or North America remains very low. The people at serious risk are those living in Ituri and the neighbouring provinces of Uganda and South Sudan, and, as always, the healthcare workers responding under extremely difficult conditions.

In my previous post I covered the background to the hantavirus outbreak on the cruise ship MV Hondius. At that point, it was largely a matter of interest among the infectious disease community, with only a faint interest from the press. Things have changed substantially in the past few days, with widespread media interest and a significant amount of anxiety among parts of the public - perhaps unsurprising given the recent pandemic.

The situation has evolved rapidly and we have much more information now to give us a better handle of where we stand and the risks going forward.

Confirmed and suspected cases

As of 8 May 2026, authorities have identified at least nine confirmed or suspected hantavirus cases linked directly to the outbreak, including three deaths: a Dutch couple and a German passenger. Confirmed infections include a critically ill British expedition guide evacuated to the Netherlands and a Swiss passenger diagnosed after leaving the ship at St Helena. Additional suspected cases include the ship’s Dutch doctor, a German passenger, and two symptomatic crew/passengers still under monitoring. As of this morning, an additional British passenger on the remote Atlantic island of Trista da Cunha is now also considered a suspected case.

There has been much interest in two potential cases in people who were not passengers aboard the ship, but had been in contact with them on their flights home. A Dutch KLM flight attendant who interacted with the infected Dutch woman in Johannesburg was hospitalised with mild symptoms but has now reportedly tested negative for hantavirus, according to WHO. Meanwhile, French authorities are monitoring a French national identified through contact tracing after sharing a flight with an infected passenger; officials say this person is currently considered a “contact case” only, with test results still awaited and no confirmed infection announced so far.

Genomic testing

There have been two important developments in the genomic assessment of the hantavirus involved in the outbreak. South African scientists have confirmed that the virus has been identified as the Andes virus. This makes sense in the context of the outbreak, as this is the only hantavirus previously documented to have caused human-to-human (H2H) transmission; it seems very likely given the distribution of cases that H2H transmission occurred on board the ship.

This is useful to know, as it highlights that the current features of the outbreak are consistent with existing knowledge of outbreaks with this virus. This means nothing unexpected has happened so far. The only unusual feature is that the outbreak has occurred on a cruise ship. However, we know that outbreaks of infectious diseases on cruise ships generally are a frequent occurrence.

The next development is that the same scientists have commented more broadly on the genetic sequencing of the virus, to report that it seems closely related to other identified Andes viruses from South America and does not appear to have any usual or distinguishing features present which would indicate it might have acquired additional or unusual features in it’s transmission or disease.

Put together, this means that nothing so far has happened which would be unexpected for this virus, and we have no indication as yet that we would anticipate anything unusual to occur.

Why this won’t be the next pandemic

Previous outbreaks of Andes virus strongly suggest that transmission is inefficient, requires close contact, and has never demonstrated the sustained community spread needed for a pandemic.

The first well-documented person-to-person Andes hantavirus outbreak occurred in southern Argentina in 1996. Investigators identified 20 linked cases, including healthcare workers and family members, with epidemiologic and later molecular evidence supporting human transmission. Genetic sequencing showed identical viral genomes among linked patients, strongly indicating direct spread rather than repeated rodent exposure.

Subsequent studies confirmed similar patterns. A 2005 CDC review documented several Argentine household and hospital clusters in which transmission occurred primarily among spouses, caregivers, or people with prolonged close exposure during the symptomatic phase of illness. In another detailed Argentine cluster from 2014, whole-genome sequencing confirmed transmission between three closely linked patients. Researchers noted that infection generally occurred during the prodromal phase, when patients were already visibly ill, and incubation periods ranged from roughly 9–40 days.

The largest modern event occurred in Epuyén, Argentina (2018–2019), where one zoonotic spillover infection triggered a cluster of 34 cases and 11 deaths after several symptomatic individuals attended crowded social gatherings. A NEJM review described this as a “super-spreader outbreak,” but even there, transmission chains remained relatively short and geographically contained.

This means there are several reasons why we do not expect Andes hantavirus to cause a COVID-scale pandemic:

• Transmission appears to require close, prolonged exposure, often among household contacts, intimate partners, caregivers, or people sharing enclosed spaces. Casual encounters rarely lead to infection.

• Patients are believed to become infectious mainly after symptoms begin, unlike SARS-CoV-2 which spreads efficiently before symptom onset. This makes contact tracing and isolation much more effective.

• Andes virus has a relatively low reproductive number (R₀) in most observed outbreaks, often estimated below or near 1 outside exceptional superspreading circumstances.

• The virus is biologically less adapted to human transmission than respiratory viruses such as influenza or coronaviruses; its primary ecological reservoir remains rodents in South America.

• As mentioned above, scientists involved in the sequencing of this Andes virus have said there is currently “nothing unusual” in the outbreak genome compared with previously circulating Andes strains.

For these reasons, the current cruise ship outbreak is considered as a serious but containable international cluster rather than the start of a globally transmissible pandemic.

The key learning points so far

Just because this outbreak isn’t unexpected doesn’t mean we shouldn’t be concerned. In fact, it shows we have not been concerned enough about hantavirus, or other viral haemorrhagic fevers previously. Whilst similar outbreaks have occurred before, they haven’t garnered interest because they haven’t impacted affluent, western populations. That needs to change. We need more research investment in this diseases because they are already impacting people in low-and-middle-income settings, and because in an increasingly globalised world, they are more likely to end up on our doorstep.

Finally, an important reason we can be confident this won’t become a pandemic is due to the rapid and diligent response and co-ordination of international and local public health agencies. Without them, things could quickly get out of control. We need them in the modern world more than ever before, and we need to make sure these agencies receive the funding and resources they need to keep us safe now, and in the future.

Summary

As of the morning of May 8th there are now 9 suspected or confirmed cases, all of whom were passengers on board the ship. There are no secondary cases of contacts from ships passengers to date, with contact tracing ongoing. The virus has been confirmed as the Andes hantavirus, which is known to cause H2H transmission which is highly likely to have occurred in this case. There are no unusual features in it’s genome which would cause us to expect this outbreak to behave differently to previous outbreaks.

Given all we know about the Andes virus and the extensive efforts being put into contact tracing and containment, the likelihood of the current outbreak turning into a pandemic is close to zero.

Diseases like hantavirus are important, and research into them is underfunded. In an increasingly globalised society, more funding is needed for research and public health agencies to keep us safe from serious and transmissible pathogens.

This week has brought some unexpected news to the infectious disease community. The WHO issued a Disease Outbreak News notification on 4 May 2026 about a hantavirus cluster aboard the MV Hondius. Not many people have heard of this disease, but the setting is unusual. The implications, depending on what investigations reveal, may be significant.

Here is an explainer on hantavirus disease, the current outbreak, and current options for treatment and prevention.

What is hantavirus?

Hantavirus disease is caused by multiple hantaviruses; a family of RNA viruses carried by rodents (primarily rats, mice, and voles, depending on the species and the part of the world). Humans typically become infected by inhaling aerosolised particles from rodent urine, droppings, or saliva. The classic scenario involves disturbing dust in an enclosed space where rodents have been living, such as cleaning out a long-disused shed, or sleeping in a cabin with an unnoticed infestation.

Direct rodent bites can also transmit infection, but airborne exposure to contaminated dust is much more common. Crucially, person-to-person transmission is extremely rare. There is one important exception, which is the Andes virus. This particular virus is found in Chile and Argentina, and has been documented to occasionally pass between humans, particularly close household contacts.

Hantaviruses cause two distinct clinical syndromes, broadly mapping to geography:

Haemorrhagic fever with renal syndrome (HFRS) is caused mainly by Hantaan virus in Asia and Puumala virus in Europe and Scandinavia. The kidneys are the principal target, and the disease ranges from a mild flu-like illness to severe organ failure with bleeding.

Hantavirus pulmonary syndrome (HPS) is caused mainly by Sin Nombre virus in North America and Andes virus in South America. Here the lungs are most affected. The clinical course is characteristic: a few days of non-specific fever, muscle aches, and gastrointestinal symptoms, followed by rapid deterioration as the lungs fill with fluid. Acute respiratory distress syndrome and shock can develop within hours.

Hantavirus disease is extremely severe. Case fatality for HPS sits at 35–40%, even with modern intensive care. HFRS is generally less lethal but still kills 1–15% of those infected, depending on the species involved.

The good news is that Hantavirus infection is very rare. Fewer than 900 cases of HPS were recorded in the United States between the start of surveillance in 1993 and the end of 2023. It is the kind of disease most clinicians will never encounter in their careers.

What is the current outbreak?

The MV Hondius, a Dutch-flagged expedition cruise ship operated by Oceanwide Expeditions, departed Ushuaia in southern Argentina on 1 April 2026 across the South Atlantic. There were ~150 people on board in total.

Between 6 and 28 April, passengers began falling ill. According to the WHO, the clinical picture was striking: fever and gastrointestinal symptoms, followed by rapid progression to pneumonia, ARDS, and shock. These are the classic features of severe hantavirus pulmonary syndrome.

As of the WHO update on 4 May, there were two laboratory-confirmed cases and five suspected cases. Three patients had died, one was critically ill, and three had milder symptoms. Two of the early cases (a couple) had travelled in Argentina, including hantavirus-endemic regions, before boarding the ship. This might fit with the disease being caused by the Andes virus, but the specific Hantavirus is yet unknown.

Two plausible mechanisms are being considered. The first is that the ship became contaminated, perhaps by infected rodents at port, with passengers exposed via dust or surfaces. The second would be more concerning: human-to-human transmission of Andes virus, which would represent one of the largest such clusters ever documented.

What are the clinic implications?

• The global risk is low. The WHO has been clear on this point, and there is no case for travel restrictions or public alarm.

• The local risk to those on the ship is significant, particularly given the limitations on intensive care available at sea.

• Whether human-to-human transmission is occurring will be the key question to resolve.

The ship is currently anchored off Praia, the capital of Cape Verde, after being refused entry to port. Medical assessments have been organised for the sickest patients, contact tracing is underway (including for passengers on a Johannesburg-bound flight that one of the cases boarded before her death), and laboratory investigations are ongoing.

Are there any treatments?

There is no specific antiviral therapy proven effective against hantavirus. Care is largely supportive: oxygen, mechanical ventilation, careful fluid management, and in the most severe cases, ECMO (heart-lung bypass) to take over for failing lungs. The key factor is access to a centre that can deliver this level of care quickly, which is why a cluster on a cruise ship in the middle of the ocean is such a concern.

As is true for all the viruses which cause deadly haemorrhagic fevers, what we really need is a vaccine. The picture here is more interesting.

Inactivated hantavirus vaccines have been used in South Korea and China for decades against HFRS, with mixed views on their effectiveness. In the West, no hantavirus vaccine is licensed. Several candidates are in early-phase development, including DNA vaccines targeting the Hantaan, Puumala, and Andes virus glycoproteins, with encouraging immunogenicity data from Phase 1 trials.

I have particular interest in this topic, as I am the Principal Investigator of an ongoing Phase 1 hantavirus vaccine clinical trial (ISRCTN17868912), which has now completed enrolment. The vaccine (MVA-Hanta) has been developed by the UKHSA using a backbone of Modified Vaccinia Ankara (MVA) - the virus which was used as the smallpox vaccine. The MVA virus has no relationship to hantaviruses itself, but it can be modified to encode for antigens which are found in other viruses (or bacteria).

Unfortunately this trial, and the other phase I trials, are still too early in the life cycle of development to provide clinical benefit towards outbreaks. Hopefully we are not too far off moving to phase II trials and being able to offer protection during rare outbreak scenarios.

Summary

Hantavirus disease is severe, and presents differently depending on which part of the world it occurs (due to different hantavirus disease causing viruses being implicated). In Europe/Asia is presents mostly as Haemorrhagic Fever with Renal Syndrome, and in South America as the more severe Hantavirus pulmonary syndrome. Treatment options remain limited and are mainly supportive. Vaccines are coming, but slowly.

A hantavirus outbreak on a cruise ship is highly unusual and concerning event. For the wider public, the risk remains very, very low. Hantavirus is not going to start spreading through the general population like COVID-19 or influenza. This is not the start of a new pandemic, and there is no reason for people outside of the ship to worry.

It remains to be seen whether the outbreak is deemed to be caused by the presence of hantavirus carrying rodents on-board the ship, or the more concerning possibility of human-to-human transmission (with involvement of the Andes virus). Hopefully further laboratory analysis and outbreak investigation will yield some more definitive answers.

All parents will be familiar with the endless onslaught of childhood illnesses once your child enters their first educational environment - be that nursery, pre-school, or school. There seems to be much confusion as to the significance of getting - or not getting - these infections. Post pandemic, the world seems to have been split into two camps; those who wish to stop their children getting these infections at all, and those who think “the sooner the better”.

As with many things, the reality is more complex.

Infected now or later?

It’s important to note that infections with most common endemic pathogens is inevitable - and for most of them, will be experienced multiple times over the life course. For some, such as rhinovirus and some of the human coronaviruses, this may even be multiple times per year. Immunity that prevents infection is short lived, either due to modest immune responses or the virus frequently changing it’s appearance to circumvent existing immunity.

One thing that is true for these bugs - it is almost always much better to get them for the first time as a young child, and probably better to get them multiple times.

This is because the immune system is set up differently in children compared to adults. There is a qualitative difference that is designed to reflect what is happening at these life stages. Children’s immune systems are programmed in preparation to encounter pathogens for the first time. Children produce a much more pronounced immediate innate immune response - the part of the immune system which recognises general patterns and is not pathogen specific - and rapid onset of inflammation. This buys time for their adaptive immune system - the part which learns to recognise specific pathogens and deploy a highly targeted and effective response - to kick into action, and mainly to be ready for when that pathogen is encountered in future.

After the first encounter, multiple exposures allow the adaptive immune system to hone and refine its response to the pathogen. This is why for most people, by the time we are adults, the same viruses which cause fevers and debilitating symptoms in young children bounce off us with often no symptoms at all.

Examples

The most obvious recent example of this phenomenon was COVID-19. Children experienced by far the mildest form of illness from the SARS-CoV-2 virus. It was in almost every respect indistinguishable from other benign respiratory viruses. For adults however, prior to vaccination it carried a remarkable rate of hospitalisation and risk of death when compared to counterparts like influenza. We were fortunate to develop vaccines for adults to use, but by the time today’s children are adults, they will have been exposed to SARS-CoV-2 so many times that it will be a trivial infection for their immune system to deal with, much like the other human coronaviruses.

There are other interesting examples. Influenza is a nasty virus. We know it now as being particularly severe for young children compared to adults - but that is only because the adult population have all been exposed multiple times and generated an impressive immune repertoire. Prior to the advent of global travel, there are accounts of influenza being introduced for the first time to small cohorts of isolated populations to dramatic effect - with mortality rates up to 20% or higher among adults in Samoa during the 1918 influenza pandemic.

Measles was similar. Prior to vaccination it was known as an illness of childhood, and even for children it was a very nasty disease. However, it was far better to have caught it as a child than as an adult. When measles was introduced into small, immune naïve populations of adults it absolutely ravaged them. In the 1850’s measles tore through Hawaii and killed ~20% of the population.

In this sense, childhood is not simply a vulnerable period, but a training phase.

For many endemic respiratory viruses and common childhood infections, this training happens early and repeatedly. By adulthood, most people carry a layered history of exposures that shapes how their immune system responds to future threats. This is why truly “novel” infections are relatively rare in adults, and when they do occur, they can be disproportionately severe.

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The younger the better?

This is where things become a little complicated. Whilst it is almost always better to get these infectionsp during childhood, the first year of life is particularly vulnerable. A good example of this is RSV, the virus which causes bronchiolitis and is the most common cause of hospitalisation of infants in the modern era. RSV exposure is ubiquitous in early life, with 90% of children having caught it by the age of two. However, evidence suggests that the severity of infection for RSV is much more strongly determined by the age at infection than whether you have been infected before. This is a good example of where being a little bit older provides better protection than having existing immunity.

Whilst the first year of life is relatively vulnerable, the period which is most exposed is the neonatal period - the first four to eight weeks of life. This is not necessarily just due to the set up of the immune system, but the developing respiratory and gastrointestinal systems which are less resilient to the onset of infection and inflammation. The protection provided by mothers during this period is absolutely key.

Since the newborn has none of their own adaptive immunity - having not yet encountered any pathogens for themselves, they are entirely reliant on immunity transferred to them from their mother. During the third trimester of pregnancy, the placenta actively transfers maternal immunoglobulins (antibodies) to the infant (more specifically immunoglobulin G, or IgG). This gives surprisingly good protection for the following three to six months. The difference between having this or not can be profound. Varicella (chicken pox) caught by a newborn in the postnatal period whose mum has transferred anti-varicella IgG to them is likely to experience a very mild illness. However, varicella caught by a newborn with no maternal IgG protection is at risk of life threatening infection and needs urgent medical treatment.

Nursery vs pre-school - does timing matter?

Outside of the neonatal period, and particularly past 9-12 months of age, the timings of these first infections does not matter too much. The infections are almost all unavoidable, and it will not make a huge difference to the child at which point they first start catching them.

A new study from Germany has examined this in some detail. The findings were that, as you would expect, entering nursery significantly increased the number of infections at this point in life compared to not going to nursery. Reassuringly however, this didn’t seem to significantly increase the total number of illness episodes. The increase at an early age seemed almost completely offset by a decrease at the older ages when other children would be entering preschool or school.

This is essentially shifting the burden earlier without any significant effect on the total burden of infections.

This also didn’t seem to make a significant difference to healthcare utilisation overall - simply shifting the time period during which this is utilised.

Infections are not “good”

It may seem silly to say it - but given a lot of confusion on this topic it’s good to be clear.

It is not good for your children, or you, to get infections.

In an ideal world, we would enable children to avoid these pathogens altogether. However, for many endemic viruses this is impossible and so we have to deal with the reality we live in. If we consider it is inevitable that these infections will occur, and all other things being equal, it is simply better to encounter them for the first time in early life. When it becomes possible to avoid the infection completely - for example, by vaccinating against chicken pox or measles - this will always be the preferred option.

There is also no evidence that countering multiple infections during childhood “boosts” the immune system in any general sense, or helps it to function appropriately. The theory parallel to this it the “hygiene hypothesis”, which is more to do with encountering normal, harmless commensal organisms, of the sort that live peacefully on your skin or within your gut. A lack of diversity among these is theorised to increase the risk of allergy or immune dysregulation, as your immune system is not adequately set up to differentiate friend from foe. According to this theory, playing in the dirt would be considered beneficial. Not so for catching influenza and RSV.

Summary

There are a huge array of ubiquitous childhood infections that must be encountered at some point. Children are uniquely designed to meet these organisms for the first time, and having multiple encounters during childhood leads to these infections being mild or trivial in adulthood. Many of these infections can be more severe during the first few months of life, but are usually less severe once over 6 - 12 months of age. It doesn’t seem to matter whether these infections are encountered earlier, during nursery, or later during school periods. The total burden seems to be the same, only shifted earlier or later.

The UK news is full of reports of an outbreak of infection with the bacteria Neisseria meningitidis, more commonly known as Meningococcus. Due to the severity of the infection, this has understandably been the source of intense interest and anxiety among the public. But what is Meningococcus, and what has happened in this outbreak?

The Meningococcus

Neisseria meningitidis was first discovered by an Austrian bacteriologist in 1887, in the cerebrospinal fluid of patients suffering from meningitis. Indeed, the bacteria is most famous for causing meningitis (infection around the brain), but can also cause bacteraemia (infection in the blood stream, also known as “septicaemia”). Bacteraemia is responsible for the classic sign of the non-blanching rash - the famous rash which does not disappear when pressure with glass is applied. When these appear as spots they are known as petechiae, and when they grow and coalesce into a patch like a bruise they are called purpura. Very severe purpura can lead to skin and tissue breakdown in the hands and feet, which in some cases can require amputation.

Notably, meningitis alone will not cause this rash. Despite the glass test being considered a test for meningitis, it is more accurate to think of it as a test for meningococcal bacteraemia.

Both infection around the brain or in the blood can lead to sepsis - an overwhelming immune response to infection which can be life threatening. The reason this infection is so dangerous is the speed with which sepsis develops. Children in particular can go from looking relatively well to having life threatening symptoms in minutes to hours.

Despite the severity of infection, the bacteria itself is extremely easy to kill. A single dose of antibiotics is usually enough to almost completely sterilise the blood or cerebrospinal fluid. A treatment course for uncomplicated bacterial meningitis with Meningococcus is only five days long - compared to 14 days for Group B Streptococcus or 21 days for E coli.

Thankfully, invasive meningococcal disease is extremely rare in the UK. During 2024/2025, there were only 378 total cases in England and around 30 deaths. Around 1/3 of all cases were in children <15yrs. Those aged 15 - 25yrs made up around 25% of cases. This rarity is largely thanks to the success of vaccination.

The outbreak

As of March 19th, there have been 15 confirmed cases and 12 suspected cases of invasive Meningococcal disease linked to the outbreak (this will be a combination of meningitis and bacteraemia). There have sadly been two deaths. The cases have occurred in the county of Kent in South East England, all linked to the city of Canterbury. Almost all the cases were linked to the same university, and the majority linked to attendance of a particular nightclub over a three day period.

There is no good explanation for why such an intense outbreak has occurred, but this is not an unknown phenomenon. My own university (Southampton) experienced an outbreak of MenC in 1997, with 6 students affected and three deaths. Most cases were linked to a shared nightclub attendance. A similar outbreak occurred in Wales the year before. More recently, the university of Surrey experienced a cluster of three cases in 2017. The current outbreak has been notable for a much higher number of cases, which remains unexplained. It is conceivable that pandemic restrictions reduced mixing and subsequent carriage rates, temporarily reducing immunity. This is reflected in the temporary drop in cases during 2020/21, but why an outbreak would only occur now is unclear and this remains speculative.

Despite high rates of carriage, the bacteria is not thought to be highly transmissible. Normally, only “kissing contacts” are thought to be at risk following cases of invasive disease and offered prophylaxis, and it is unclear why sporadic outbreaks occur in different settings such as universities, or nurseries.

The current outbreak is considered to have been contained, with the response of the UKHSA having been to offer prophylactic antibiotics to any attendees of the nightclub during the affected period, and close contacts of any of the known cases. In addition, students at the affected university at the relevant campus or who attended the nightclub during the relevant period are also now being offered a vaccine against the specific serogroup of Meningococcus indicated in the outbreak - MenB.

Vaccination

The current UK vaccine schedule does include vaccination against MenB, but only for infants This was introduced in 2015. Teenagers received a different meningococcal vaccine, which is against serogroups ACWY.

The reasons for this difference in infant and adolescent vaccination are all to do with carriage.

Meningococcus is a normal commensal bacteria in the mouth and throat, carried by around 10% - 35% of people, with the highest rates in older teenagers/young adults. This makes them the main reservoir for Meningococcal transmission. The MenACWY vaccine is extremely effective, not just at preventing severe illness, but also preventing carriage. This means that vaccinating teenagers protects the entire population, as it halts the main route of transmission of these serogroups. The reason we no longer need to vaccinate infants against MenC (previously the most common cause of invasive Meningococcal disease) is because we have effectively eliminated carriage of this serogroup by vaccinating teenagers.

Alas, the same is not true of MenB. Whilst the MenACWY vaccine effectively targets the polysaccharide capsule surrounding the bacteria, we cannot do this for MenB. Its capsular polysaccharide too closely resembles human neural tissue, risks causing the body to attack itself and appears relatively un-immunogenic in pre-clinical models.

The other antigens available to target are highly diverse, meaning that several have had to be combined to try and get the best possible coverage, but still leaves some strains uncovered. Disappointingly, the vaccine also fails to prevent transmission of carriage among young adults, as demonstrated in RCTs. This means vaccinating teenagers has not been cost effective, as invasive disease is very rare and there are no benefits to others from vaccinating them. Protection from the vaccine is also relatively short lived, so future adolescents who were vaccinated as infants will have relatively little protection by the time they attend university.

The current outbreak is likely to provoke strong feelings amongst some about the need to vaccinate teenagers against MenB. The JCVI (who determine the recommendations) operate on strict criteria for cost effectiveness. It remains to be seen whether the most up-to-date epidemiology and modelling would tip this over into being a good decision based on these criteria, but it seems unlikely a single outbreak would have much impact.

Summary

Neisseria meningitidis is a bacteria which can cause life threatening infection around the brain or in the blood, leading to sepsis. It has cause an outbreak in at least 20 university students in South East England, with a some deaths. The outbreak is caused by the MenB serogroup, which infants are vaccinated against, but adolescents are not. This is because the vaccine does not prevent carriage; unlike the MenACWY vaccine currently offered. It is unclear if there is a case for offering routine vaccination to adolescents in the future.

Until recently, most parents had never heard of Respiratory Syncytial Virus (RSV). This is remarkable, given it is the major winter scourge of child health. Whilst influenza, rightly, has a reputation for causing pressure on health services, RSV actually poses a much larger burden in paediatrics. Entire ward bays are dedicated to babies and young children with RSV infection every winter. This usually presents as the syndrome known as “bronchiolitis”, characterised by difficulty breathing, wheezing and crackles on the lungs, and difficulty feeding. It is the most common reason for children to need hospitalisation in the UK and high income countries. It costs the UK economy around £80 million per year. There is no treatment, and the management is just supporting babies whilst their immune systems fends off the invader.

Despite the revolution in child health brought about by vaccination in the last 25 years, RSV remained the major pathogen for healthy children for which we had no protection.

That has now changed.

Why didn’t we have vaccines for RSV?

Due to it’s significance, RSV has long been a target for vaccination. Some of the earliest efforts were made in 1966 and were made from formalin inactivated RSV viruses - a relatively common technique.

However, this is where we ran into problems. In the trials of these vaccines, far from protecting infants against RSV infection, it looked as though the vaccines seemed to somehow make infections worse. Sadly, two children who received these early vaccines died and many more were hospitalised with severe infection. This is one of the earliest examples of something called vaccine associated enhanced respiratory disease (VAERD), where the reaction to vaccination creates an aberrant immune response when infection is next encountered, resulting in much more severe disease. It was later noted that the formalin inactivated vaccines only generated antibodies to the F protein (the most immunogenic antigen) in its post fusion form - the way it looks after binding to cells. It was theorised that targeting only the pre-fusion version might avert VAERD, and all therapeutics have been targeted at the pre-fusion F protein (RSVpreF) ever since.

This major setback caused a lot of anxiety about producing vaccines for young children, delaying progress in the field for a long time. This is why we’ve had no options for protecting otherwise healthy children - until now. Remarkably, in the past two years we have gained two novel methods of protection.

Monoclonal antibodies

Vaccines work by showing your immune system a portion, or weakened version of a pathogen, training it to make antibodies itself. But there is an alternative approach. If you know precisely what portion of a pathogen is best to target, you can externally manufacture antibodies against it and then administer them to people directly. These are called monoclonal antibodies. They usually don’t last long, and are expensive to manufacture - but they work. A version of this for RSV called palivizumab already existed, but it only worked for 1 month at a time. This meant only babies with profound susceptibility to RSV were eligible, and needed monthly injections during winter to stay protected.

More recently, a long acting monclonal antibody called nirsevimab came along. It provided amazing results in phase III trials, then in the pivotal HARMONIE clinical trial was shown to reduce RSV hospitalisation by 80% over the first RSV season, and remarkably, reduced all cause respiratory hospitalisations in babies by half. It lasts for a whole RSV season (at least), suitable for all babies to get protected from RSV.

It was implemented very early after licensure in some areas, including Galicia in Spain, where very high uptake by babies resulted in dramatic falls in hospital admissions from RSV over the following season. This is the first real “game changer”, in paediatrics for decades. But it doesn’t end there.

Maternal vaccination

The issues encountered by RSV vaccination in infants seemed to be restricted to babies who hadn’t seen RSV before. If you already had an existing immune profile to RSV, vaccination seemed to just enhance your existing response rather than resulting in an aberrant one. This has led to much faster development of excellent vaccines for the elderly, and for pregnant mums.

Maternal vaccination is ingenious. Newborn babies obviously have no existing adaptive immune profile - they’ve never encountered any pathogens of their own. To help protect them, their mothers antibodies (specifically IgG) are actively transferred to babies across the placenta during the third trimester. This gives babies pretty good antibody protection for the first three to six months of life. By boosting maternal antibody levels to pathogens which are particularly dangerous to newborns, you can enhance the newborns protection by giving them more of their mum’s antibodies. We already do this for pertussis and flu - now we can do it for RSV too.

Phase III clinical trials showed impressive protection for babies whose mothers were vaccinated against RSV during pregnancy at levels which look very similar to those provided by immunisation with nirsevimab (the trials are different in many ways which preclude direct comparison - but they are in the same ball-park). This is now the main form of protection offered in the UK, with monoclonal antibodies only offered to very high risk infants (who would previously have received palivizumab).

Both monoclonal antibodies and maternal vaccination work in a similar way - by providing babies with antibodies they didn’t make themselves to give them effective, but temporary protection during the period where they are most vulnerable.

What about infant vaccination?

Whilst temporary protection is much better than nothing, there remains a desire to give infants vaccination which could provide long term protection - enabling them to produce an enduring response to RSV for all future encounters, and not just for the few months where they are highest risk. Whilst the spectre of VAERD loomed over RSV vaccination, extensive efforts have been made to try and understand the mechanisms by which it happened. Several safeguards were put in place to eliminate any candidates at the pre-clinical stage which looked like they might induce it.1

Vaccine trials commenced with several candidates, including those made by the novel mRNA platforms which were so successful for COVID-19. But sadly, things did not go entirely as planned.

At the very early stages of clinical trials for mRNA RSV vaccines, a small imbalance in severe RSV infections were noticed in the vaccination groups compared to the placebo arms (but fortunately no deaths). The trials were immediately halted and a meeting of drug regulators was convened on December 12th 2024. Despite the vaccine passing all the pre-clinical tests put in place to ensure the vaccines didn’t result in VAERD, it looks possible it may have happened anyway. The good news is that all the safety checks put in place to catch it early at the clinical phase worked extremely well.

The outcome of the meeting was that all clinical trials for RSV vaccines in children under two years old, or under five years old with no evidence of prior RSV exposure were put on-hold (with the exception of live, attenuated vaccines).2 Further scientific work will be needed to provide additional reassurances for study of future vaccine candidates, and robust safety plans in place to detect any possible incidences of VAERD.

What next?

There are promising candidates for RSV vaccination for children - most notably, a nasal spray of a live, attenuated RSV virus. This would be similar to the current nasal influenza vaccine used for children aged two and older (known as Fluenz in the UK and Flumist in the US). The vaccine brings the added benefit of involving no needles, making it more acceptable for children and their parents alike. Many of us are eagerly awaiting to hear progress on the further information needed by the FDA to move forwards with clinical trials.

In the meantime, we are fortunate to have two alternatives to protect infants during their most vulnerable stages in life - passive immunisation with monoclonal antibodies or maternal vaccination. The key for these interventions will be in ensuring uptake. The UK managed a pretty miserable 55% uptake of maternal vaccination during it’s first year, and it was given to pregnant mothers too late to have any impact on the first RSV season (much to the frustration of paediatricians around the country). Hopefully this year we will begin to see an impact - although this will only be as good as the uptake we manage to achieve.

This is no small task in an era where the worlds main superpower has an avowed anti-vaxxer in charge of it’s health service, and who has filled their own vaccine advisory board with other anti-vaxxers. The public have never received such a barrage of confusing, and downright false information regarding vaccines from the people they are meant to be able to trust. It is more important than ever that professionals in the UK step up to provide the English speaking world with clear, open, and trustworthy communications about vaccination to improve public confidence.

Summary

RSV is a major cause of respiratory morbidity in young infants. Until recently, we had no way to protect babies. Now we are able to provide them with maternal vaccination or monoclonal antibodies to keep them safe during their most vulnerable periods. Health professionals must focus on improving confidence and trust in the provision of these therapies to help keep babies safe. Infant vaccination remains someway in the distance due to recent setbacks in potential VAERD, but promising candidates remain.

We’ve come a very long way in infant protection from RSV - but there is further we can go still.

One of the most noteworthy phenomena since the Covid-19 pandemic has been the erratic, sometimes explosive recurrence of seasonal infections such as RSV and Group A Strep. Many people have attributed this phenomenon to something termed “immunity debt”, sparking a huge amount of debate online and even in the media as to what this means. Some outlets even referred to the idea as “misguided and dangerous”.

My colleague Thomas House and I recently published an article on the issue in the journal “Clinical Infectious Diseases”, and a brand new publication has shone some new light on the topic. I thought this would be an excellent opportunity to explain this concept and clear up some of the confusion and controversy around it.

Normal seasonal pathogen circulation

Some pathogens such as RSV and Group A Strep are “endemic”, which broadly means they are always circulating to some extent. They are also seasonal, meaning rather than circulating at a constant level, they come and go in annual waves. There are several reasons this happens, however one of the most important is levels of population immunity.

During a wave of infections, exposure to these pathogens causes a boost to peoples immunity. This includes people who were last exposed a while ago, or to young children who have never been exposed before. This causes the level of population immunity to rise. Once it’s high enough, it becomes too difficult for the pathogen to continue to circulate and the wave of infections rescinds.

After the next few months, population immunity gradually falls again and new children are born who have never been exposed. Eventually, population immunity is low enough for another wave of infections to occur. This occurs in a relatively predictable pattern, so there is a rough range of “normal” levels of immunity.

What happened during the pandemic?

Measures used to prevent the circulation of Covid-19 had a predictable impact on also preventing the circulation of other infections. In fact, it was so successful in some cases we think it actually caused the extinction of an entire strain of influenza (the Yamagata strain). As seasonal pathogens did not circulate at their usual time, this causes population immunity to fall lower than it usually would. This is because immunity falls over time since the last exposure, and more children than usual had been born who had never been exposed.

We knew this would happen, and it was predicted that this would cause disruption to the circulation of these pathogens when they recurred.

What is immunity debt?

Immunity debt is simply the term derived to explain population immunity being lower than what would be normal for a particular pathogen. The term “debt” refers to an amount of additional immunity needed to be accrued to cause the seasonal wave to decrease compared to normal, as it is starting from a lower baseline. This is what would explain the larger than usual number of infections observed for the recurrence of pathogens such as RSV or Group A Strep; or even the current epidemic of Mycoplasma pneumoniae being observed in North America (much of the rest of the world experienced this in winter 2023/24).

Some people mistook the term to mean a general phenomenon where the immune system needs constant exposure to a variety of pathogens in order to be “strong”. This is not what it means. It is about immunity to specific pathogens which usually occur in cycles. It has never been referred to in this way in the academic literature or by any specialists in infectious diseases or immunology.

Is Covid-19 impacting immunity?

A small community of people have claimed that these increased waves of infection are happening due to Covid-19 causing immunodeficiency in children and adults. Some have even gone so far as to refer to Covid-19 as “airborne AIDS”. This is completely false. There is no evidence of Covid-19 causing any clinically relevant changes to the immune system beyond that which is seen with all viral infections during the acute infection. I have previously written about this disastrously wrong theory which you can read below.

What’s the new research?

An excellent new study from a paediatric emergency medicine network has provided more evidence towards the theory of immunity debt. They tracked the levels of several seasonal infections during and after the pandemic, looking for a “dose response” relationship between how much each infection was suppressed during the pandemic and how great the level of the infection was when it recurred. As per the theory of immunity debt, we would expect that pathogens which were suppressed more to have a higher rebound in infections. If there was any problem with immunity due to Covid-19 infections, there is no reason why this would happen and the recurrence of infections would have no reason to be proportional to their suppression.

It should be no surprise that we observed precisely what we would expect based on our existing knowledge of infectious disease transmission and population immunity. There was a clear dose response relationship between infection suppression and recurrence, during and after the pandemic respectively. Such a correlation was not observed for urinary tract infections, used as a control as they would not be expected to be impacted by non-pharmaceutical interventions and therefore by immunity debt. This provides excellent evidence for the theory of immunity debt as the explanation for the phenomenon we have observed after the pandemic with the circulation of seasonal infectious diseases.

Furthermore, all the pathogens which had unusual surges post-pandemic so far have already settled back into their normal circulation patterns. RSV and Group A Strep are now behaving as normal. This is again what we would expect according to the theory of immunity debt, and is not what would happen if Covid-19 was impacting children’s immunity.

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Summary

Immunity debt describes the lower than normal levels of population immunity to seasonal pathogens which occurred after the pandemic due to the suppression of these pathogens as a side effect of the interventions to suppress Covid-19. This was expected prior to the pandemic, and has happened according to what we would expect. A new study has demonstrated a dose-response relationship to infection suppression and recurrence which provides further evidence towards this theory. There is no clinical or epidemiological evidence of Covid-19 causing any relevant immunodeficiency in the population.

For a more technical and detailed discussion you can read the open access version of my publication with Thomas House here.