Zika – still in muddy water

The spread of Zika in Brazil in 2015 ahead of the Rio 2016 Olympic Games and its reported association with microcephaly received much attention. In the event there were no cases at the Games and Zika reports faded as fast as they had arrived. The WHO’s statement that Zika was a global health emergency ended 9 months after it was called and Brazil’s state of emergency was also declared over 6 months later. The virus itself however has continued to spread (see timeline) and it made a brief return to notoriety this month with the first reports of cases in India[1]. As the closely related Dengue virus circulates in India it is very likely that Zika numbers will go up there but whether this should be a public concern remains hard to judge.

Infection of adults by Zika gives a mild aches and pains type of infection which resolves naturally. The issue is surrounding the virus is if women who contract the virus during pregnancy, particularly the first three months of pregnancy, have an increased risk of delivering a baby with fetal abnormalities, the most serious of which is microcephaly. This issue, does it or doesn’t it cause microcephaly, remains unclear.

Some arboviruses, that is viruses transmitted by insect bite, have long been associated with birth defects, particularly in the case of animal infections [2] but viruses that are the most related to Zika are not among them, despite circulating widely. Zika itself has been on the move since the 1950s and no association was reported before the Brazilian epidemic. The virus has been reported to have changed to a pandemic strain during this spread so it is conceivable that the “new” virus has more aggressive properties than the old, and there is some experimental evidence from laboratory studies to support this, but that too doesn’t really explain the differences in the rates of microcephaly reported in different locations.

Zika infection and cases of microcephaly (or Congenital Zika Syndrome – CZS) are tracked by the WHO and updated regularly (see [3]) but the numbers are hard to understand. Adjacent countries with similar numbers of claimed Zika infections, all by the pandemic strain, have hugely different numbers of microcephaly cases. The Dominican Republic for example claims 345 confirmed Zika infections and 93 cases of CZS, a rate of around 1 in 4 whereas Puerto Rico claims 40,274 cases and only 35 cases of CZS, a rate of less than 1 in 1000. Guatemala states 921 confirmed infections and 59 cases of CZS whereas Costa Rica, almost next door, states twice the number of infections but only 5 cases of CZS. Of course these numbers are subject to reporting errors but the reported rates of microcephaly are so different that they leave open the question of whether the virus is involved at all.
This lack of a confirmed relationship between infections and microcephaly was published as a correspondence in the New England Journal of Medicine recently with both Brazilian Ministry of Health and WHO authors [4].  This paper has not been cited as widely as it should, perhaps because, as a correspondence, no abstract appears on PubMed and similar sites, but the study is careful, clear and telling.  The authors plotted the cases of Zika infection for five regions of Brazil over the course of two complete seasons, 2015 and 2016 and co-plotted the number of cases of microcephaly and another condition attributed to Zika, Guillain–Barré Syndrome or GBS. GBS is a complication that can occur following a number of infections not just Zika and its inclusion here acts as sort of control – if there is Zika infection in the population you would expect a certain number of GBS cases to follow, and that is what is observed, for both of the years studied. But what about microcephaly?

The data is quite clear (see figure): microcephaly cases rose about 23 weeks after the Zika outbreak in 2015 (so consistent with births to mothers infected in the first trimester) but there was no such rise in numbers during 2016. There are various hypotheses to explain this discrepancy, perhaps not all the infections were Zika for example, but an obvious conclusion is that the association of Zika with microcephaly has been overstated. Their conclusion states it diplomatically “Further investigations are needed…..to clarify the causal links between arbovirus infections, GBS, and microcephaly in Brazil” – quite.

 

[1] http://www.firstpost.com/india/zika-virus-reaches-india-who-confirms-3-cases-in-ahmedabad-3488985.html

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581091/

[3] http://www.paho.org/hq/index.php?option=com_content&view=article&id=12390&Itemid=42090&lang=en

[4] http://www.nejm.org/doi/full/10.1056/NEJMc1608612

 

Zika and microcephaly: the answer is…..

The structure of Zikavirus has been published [1]. The work was done by a well known virus structure group at Purdue University and follows their previous structures of similar viruses, notably Dengue virus. Pleasingly the paper is open access so anyone can read the details and see how the virus is. It looks, well, like any other flavivirus.

zik

Zikavirus. The outside surface of the virus shows the classic “herringbone” arrangement of the major glycoprotein (the yellow), the protein that gets the virus into a cell. The virus is symmetrical and the 2-fold (oval), 3-fold (triangle) and 5-fold (pentangle) axis of symmetry are shown.  

Ordinarily, a virus structure might resolve unknowns concerning virus entry into the cell, especially if the resolution of the structure, the level of detail that can be seen, is sufficient to make out the surface detail, as the authors have managed here. So the Zika structure was awaited in the hope it might cast some light on how Zika could(still could, not proven yet) cause microcephaly.

Viruses have notable affinities for some cells more than others, termed tropism, and this is most usually governed by the virus interaction with the cell surface via a virus “receptor”. If the receptor is present the virus can enter, if it is absent it cannot. The question for Zika prior to the structure was whether the detail of the virus surface could help resolve this question. That is, what is the receptor used for foetal infection and could this explain the supposed link with microcephaly – alas it does not.

As is the case for all other arboviruses (viruses transmitted from insects) the identity of a receptor that could explain virus tropism remains unknown. There are really none that can be stated as “the” entry gate for the virus. At best all that can be said is that the position of a sugar chain on the surface of the virus, attached to the envelope (E) protein, is consistent with initial binding to a cell surface lectin (a sugar binding protein). The position is largely conserved with Dengue virus, as is most of the E structure. The position does vary a bit among related viruses so it could be part of the tropism picture but if it is the first contact with a cell then it will be a point of contact also for neutralizing antibodies produced during an infection and that, in turn, will drive change in the region through the everyday forces of evolution. In other words, the fact that this site varies is not surprising and it may have nothing to do with cell specificity.

zik2

A model for the interaction of Zika with the host cell. It’s very likely but it does not explain any specificity for foetal tissue 

The outcomes attributed to Zika have continued to grow. Soon after the first reports of microcephaly, GuillainBarré Syndrome (GBS) was added to the Zika list of possible outcomes and in neighbouring Colombia it has been linked to a creeping paralysis[2]. Could one relatively simple virus cause all of these outcomes? In the case of GBS, the underlying cause is an autoimmunity syndrome triggered by a number of different infections. It is difficult to see why Zika should be any more associated with it than any other of the previously listed causes and given that many other infections circulate with Zika proving Zika is a direct cause, let alone the only cause, will be very difficult.

A alternate view to the current sensation based reporting is that once the immediate epidemic is over[3] the immunity left in the population will naturally control subsequent infections so that the longer term outlook is not as bad as it might first seem.

[1] http://science.sciencemag.org/content/early/2016/03/30/science.aaf5316.full

[2] http://www.bbc.co.uk/news/health-35552340

[3] http://www.independent.co.uk/news/world/americas/zika-infections-decline-in-parts-of-latin-america-a6967026.html

 

Zika and Microcephaly – all aboard the speculation express

My last post ended “We must wait for the next year to see … whether or not the El Nino effect that is giving the unseasonal weather will perturb virus dynamics (those transmitted by insect pests for example) later in the year” (Another Year). Well, we didn’t have to wait long.

No one would wish to underplay the possible role of a new infection in something as sensitive as birth defects but the assumption that the current Zika outbreak is THE cause of a reported surge in cases of microcephaly among new-borns is premature. There is no doubt that a Zika epidemic is in progress in South America, fuelled by mosquito infestation, and several independent reports suggest a rise in the number of cases of microcephaly. But whether these observations are linked is much less sure. It’s not unreasonable to make the assumption, especially as not to do so would risk making light of personal tragedies, but the hard data is yet to be presented. Is it Zika and only Zika (many other viruses are transmitted by the same mosquitoes) and if so why should this virus do it and why was it not seen before (other Zika outbreaks have occurred as it moved across the Pacific albeit not on the scale now being witnessed in countries like Brazil)? In the absence of reliable data here are some virus related points that might be considered.

That Zika could be linked to microcephaly

  • The virus has been reportedly fund at autopsy of affected new-borns
  • It is circulating and will obviously infect pregnant women (~4% of the population at any one time)
  • Some viruses of this family (flaviviruses) cause encephalitis in adults
  • Other viruses like Rubella and CMV, long known to be able to transfer across the placenta and infect the foetus, cause foetal abnormalities including microcephaly
  • It is a new infection so previous experience limited, nothing should be ruled out

That Zika is unlikely to be linked to microcephaly

  • Tests for Zika are often confused by cross reaction with other flaviviruses
  • Previous Zika epidemics, in Africa, Southeast Asia, and the Pacific Islands have not noted the link with microcephaly despite detailed follow up
  • Why only microcephaly? Rubella and CMV infection result in a range of birth defects resulting from damage of many foetal tissues. Generally the earlier in the pregnancy the infection, the greater the damage. No such range reported for Zika
  • Specific brain cell infection would require a tropism for that tissue. No such tropism has been shown in adult Zika infections. In fact arboviruses (insect transmitted viruses) are known for their wide host range, infecting many cell types

From a virology perspective the case for Zika being a “microcephaly virus” is not at all clear. It is reasonable to err on the side of caution, e.g. the travel advice for pregnant women, but no-one knows the real risk assessment and we must wait for much more comprehensive follow-ups to know if the presumed association is real. It seems too widespread to be mass hysteria but with a world sensitised to virus outbreaks by the Ebola and Swine/avian flu experiences it is also prudent to question whether there isn’t a hint of scaremongering in the coverage to date.

Another year

Another year

Influenza

Seasonal times bring seasonal infections, or not as in the case of Influenza this year. As has been the case for the last three years influenza activity has been very low, in fact for this year remarkably low and if past years are a reliable guide (they mostly are) then we are already through the peak month and the winter flu outbreak is already on the slide. The amazingly warm weather is certainly part of the reason for this but it seems also that the strains in circulation are relatively unchanged from previous years and are all well-matched by the current vaccine strains, unlike the situation last year where the H3 strains in the vaccine were poorly matched[1]  although that season too was very mild.  The majority of strains typed this year so far have been H1, essentially the pandemic strain from 2009 which seems have varied very little in recent years. We haven’t had a significant flu outbreak since 2010/11 but as noted previously in this blog the clock resets itself every year and a cold snap could change what has been, for the last few years, a relatively benign influenza season.

Ebola

Any review of the year for 2015 (they will be in the supplements at the coming weekend) would have to include the end of the Ebola outbreak. So much has been written on the outbreak that more seems pointless and there will be ample papers this year with official follow-up analysis such as the case fatality rate with time (remarkably similar from early in the epidemic to late as far as I can make out which suggests the treatment camps did not improve as time went on) and the outcome of clinical trials conducted while the epidemic was raging. Whatever these say, the subject has already gone from the headlines (graphic 1), predictable but still disappointing as it was historically significant for a number of reasons.

graphic1


Others

If you strip out Ebola and Influenza then 2015 has been a relatively quiet year for virus infections (graphic 2), at least for those that might make headlines. They are all there of course causing routine

graphic2
infections throughout the year, common cold, measles (still an issue in inner London), HIV, Herpes, norovirus, but nothing has really taken off this year and those associated with the winter season have been particularly quiet. Some of this is the result of other world events dominating the headlines but there too viruses are involved with increased incidences of a number of infections, including HIV and measles, in refugee populations displaced by the war in Syria. We must wait for the next year to see how serious these become and whether or not the El Nino effect that is giving the unseasonal weather will perturb virus dynamics (those transmitted by insect pests for example) later in the year.

[1] http://www.telegraph.co.uk/news/health/news/11393560/Flu-jab-given-to-millions-is-useless.html

 

New year updates

Ebola – the magic of R0
The Ebola numbers in West Africa are in decline – hurrah. So much so in fact that the much anticipated trials of vaccine and drug interventions have had to be rescheduled or stopped as the number of cases cannot be relied upon to give a meaningful measure of effectiveness[1]. For anyone not quite clear on this, any trial of effectiveness for a lethal outbreak disease, one that does not circulate in man naturally, has to take place during an outbreak while people are being infected. There is no surrogate so splitting an at-risk population into groups that receive the treatment or not, and then looking at the rate of disease incidence over time (you are hoping to see it reduced in the test group when compared to the untreated) is the only definitive way of knowing the treatment is effective. So far the safety tests have proved satisfactory although they leave open the question of whether a single shot of the vaccine would be enough to ensure protection[2]. This is tricky as, after the immediate needs of healthcare workers and so on, any eventual vaccine would be destined for a rural population and the chance of getting them back for boosters is not simple. However the fact that a vaccine has got this far so quickly is to be welcomed although it will not play a major role in this ending this epidemic, as indeed was predicted at the onset of scale-up[3].

Capture

What HAS curtailed the epidemic is infection control, particularly the ending of risky funerary practices; there is direct link between country ebola rates and adherence to the “Safe Burials Save Lives” campaign[4]. If the virus cannot pass on to another individual it dies with the host and its basic replication rate (R0) falls below the level where the epidemic is sustainable. As long as these measures are maintained it is a mathematical certainty the outbreak will end. A disappointment for a virologist like me is the unsupported chatter about the virus changing to become less pathogenic and the case fatality rate falling[5]. There is no unambiguous data for this; as far as it goes the virus shows typical RNA quasispecies changes, not a constant drift to something else, and the CFR remains around 60% when centre effectiveness and local population profiles are adjusted. It is the same virus causing the same disease as it always has, which is why it is now responding to the traditional methods of control.

Influenza – all quiet except for the shouting

Splash headlines on the infectiveness of this year’s flu vaccine[6] do not help the general need to ensure that vaccines are taken up promptly by most of the population. Most current flu vaccine protect against 4 different viruses, 2 A strains and 2 B strains. The choice of which strain to use for the vaccine (there are many circulating across the globe) is made ahead of manufacturing and is done on a best guess basis using data on which strains predominate when positive cases are diagnosed. For 1 of the 4 strains (1 of the A strains) that guess was wrong this year. For detail, the vaccine strain used to protect against H3 subtypes (A/Texas/50/2012) turns out not to be a good match to the strain that is causing most infections (A/Switzerland/9715293/2013). The remaining 3 strains ARE a good match and do protect against the second A strain (H1) and the 2 B strains. As it happens this year has been another relatively mild year for influenza. It has scarcely made the headlines and the season is effectivity over with numbers now in decline[7].

There are 4 main pillars supporting the longevity we now expect; sanitation, nutrition, antibiotics and vaccines. Remove any of these and infectious disease will re-emerge (it has never gone away, just held down to containable levels). Tone, slant, spin, call it what you like, the delight shown by some reporting when a product fails to live up to expectation is miserable. The message should be learn from the omission and be better next time, keep up not give up.

[1] http://www.theguardian.com/world/2015/jan/23/ebola-vaccine-liberia-gsk-glaxosmithkline-trials

[2] http://www.nejm.org/doi/full/10.1056/NEJMoa1410863

[3] http://www.bbc.co.uk/news/health-29649572

[4] http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6401a6.htm

[5] http://www.bbc.co.uk/news/health-31019097

[6] http://www.telegraph.co.uk/news/health/news/11393560/Flu-jab-given-to-millions-is-useless.html

[7] https://www.gov.uk/government/statistics/weekly-national-flu-reports

Ebola, Ebola, Ebola

You don’t need to watch Donnie Darko to know that we live in a mad world. The current Ebola situation is truly dismal with numbers of cases continuing to rise in the three West African countries that form the epicentre of the infection, Guinea, Sierra Leone and Liberia. In fact there is a glimmer of improvement on the numbers tracked by WHO as both Guinea and Sierra Leone show a small flattening of the curve of known cases with time[i]; they are still rising but not as fast as previously. It is a hopeful sign that contagion control measures, previously not taken seriously enough or not applied in the right places, are beginning to take effect. In Liberia however the cases continue to rise as in a classic epidemic.

Anyone looking at these figures can tell where action needs to be taken – on the ground where the disease is still being transmitted by practices resulting from a mix of fear, shame, suspicion and ignorance, and where the infected are unable to be treated effectively as a result of a dysfunctional health care system. It is doubly disturbing therefore that the focus in the west has shifted to battening down the hatches for an epidemic we will never see. Like most of my colleagues[ii] I decry the screening of incomers at ports and airports as it is wholly pointless. Anyone showing obvious fever symptoms would have shown the same at embarkation and that is where they ought to have been identified and subjected to a full test. Anyone at the start of the up to 3 weeks incubation time will walk through anyway. What is particularly worrisome is that Mr Cameron claims he is listening to medical experts[iii] when all the experts I know say the opposite. One wonders who exactly is giving this advice and why the resource used would not be better deployed elsewhere.

Meanwhile companies in the region, providing work which pays taxes which untimely funds some healthcare provision, go bankrupt, cruise liners that would bring tourist spend go elsewhere and companies selling disinfectant are doing roaring business[iv].  The basic facts of contagion control, which could stop this disease quickly, have been quietly side-lined in favour of grandstanding.

 

[i] http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6339a4.htm?s_cid=mm6339a4_w#Fig1

[ii] http://www.independent.ie/world-news/europe/ebola-screening-at-airports-is-a-waste-of-time-30656889.html

[iii] http://www.ft.com/cms/s/0/93c54214-5097-11e4-b73e-00144feab7de.html#axzz3FxWDimhe

[iv] http://www.telegraph.co.uk/finance/markets/marketreport/11152714/Market-report-Ebola-worries-draw-attention-to-Bioquell.html

 

Ebola declared a Public Health Emergency of International Concern – yes but….

The declaration of a PHEIC (Public Health Emergency of International Concern) by WHO on Friday 8th August received a lot of press coverage (too much to list). In part it was stating the obvious as the virus had already infected individuals in 4 African countries so met the international definition. Of course the WHO release[1] contains authoritative summaries and suggested courses of action but to me the concentration on the international dimension risks missing the obvious. The miserable current situation in Western Africa is not helped by inaccurate and sensational press reporting that emphasises the risk abroad, such as the Daily Express on Wednesday the 6th which announced that the Saudi patient hospitalised on return from West Africa “had tested positive for the virus” and become the “first victim outside of Africa”[2]. Neither of these was true as reported by the Saudi Health Ministry (which did a very good job incidentally) yesterday[3]. Why sensationalise an already dire situation? The reporter concerned couldn’t possibly have had reliable information as none had been released at the time of the article.

In fact the risk to the international community is trivial compared to the situation on the ground[4] and it is there that effort is required. The point that is not getting through is that if the current virus spread in Sierra Leone, Guinea and Liberia was controlled there wouldn’t be any sick people to board aircraft. And the current talk of experimental drugs and vaccines, while worthwhile for longer term planning, also tends to drown out the simple fact that Ebola has been successfully cleaned up on many previous occasions and can be again with the appropriate actions.

Border closures and country leaders announcing a state of emergency may do some good but it is the epicentre that needs the attention and that needs money, logistics and roll-out that grand announcements ignore.

The Ebola “Secret Serum” – what is it and how does it work?

The news that both the American aid workers who have contracted Ebola have been treated with a secret serum and appear to be making a recovery will answer many calls for why there is no treatment for Ebola. I wish both patients the best possible outcome. But what is this secret serum, why hasn’t it been used before and how does it work?

In fact the “serum” is a mixture of 3 humanised monoclonal antibodies previously selected for inhibiting Ebola replication and shown to protect monkeys from Ebola infection[1]. Crucially, a study last year showed that the antibody mixture could be given post-exposure, that is once someone was already infected, and still result in about 50% protection[2]. “Serum” is an inaccurate description of the product as a naturally occurring serum, for example taken from an animal or someone who has been previously vaccinated (or infected), would contain many antibodies, only some of which would be effective in blocking virus infection. This product is much more defined; it is made of ONLY antibodies that block virus infection so the potency per volume is far higher. An added twist, although it doesn’t relate to how the antibodies work, is that each antibody was produced by expression of the protein in plants, a technology that has the possibility of cheap manufacture.  

mabs

Making the secret serum. Mice are immunized with Ebola virus, to which they mount a normal immune response. In this case the mice are transgenic and make human not mouse antibodies so down the line, if they are used in man, the antibodies themselves will not cause a reaction. The antibodies are screened for those that inhibit Ebola virus growth and those that show inhibition are isolated. The genes that encode those antibodies are isolated and put into plant cells in such a way that they make human antibodies as part of the growth of the plant. Plants are harvested and crushed and the human antibody in the sap is purified. Now, when infused into infected patients the antibody slows Ebola growth giving the patient a chance to recover. It is not a cure but a very supportive helping hand for a natural recovery. The treatment is part of the field of “therapeutic antibodies” and is already an accepted clinical practice.     

 

Will this now be rolled out in Africa? Alas probably not. Firstly, no-one knows how late in an infection the products would still work. Both aid workers were in the very centres set up to deal with Ebola so couldn’t have been in a more appropriate place. They were diagnosed very quickly and surrendered themselves for treatment. That is not the case in the rural population of western Africa. The product is not FDA approved and was used under a special “compassionate grounds” clause. This would probably not apply in Africa were local consent would need to be sought. And despite the manufacture in plants, which in theory could be growth on almost limitless scale, the product will not be cheap or plentiful in the short term. All of these facts will limit the application of therapeutic antibodies in a real outbreak situation. However, assuming a good outcome an important principle will have been proved and stockpiling of the product for use in future outbreaks may be a realistic possibility.

 

[1] Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques.Olinger GG Jr, Pettitt J, Kim D, Working C, Bohorov O, Bratcher B, Hiatt E, Hume SD, Johnson AK, Morton J, Pauly M, Whaley KJ, Lear CM, Biggins JE, Scully C, Hensley L, Zeitlin L.Proc Natl Acad Sci U S A. 2012 Oct 30;109(44):18030-5. doi: 10.1073/pnas.1213709109. Epub 2012 Oct 15
[2] Therapeutic intervention of Ebola virus infection in rhesus macaques with the MB-003 monoclonal antibody cocktail.Pettitt J, Zeitlin L, Kim do H, Working C, Johnson JC, Bohorov O, Bratcher B, Hiatt E, Hume SD, Johnson AK, Morton J, Pauly MH, Whaley KJ, Ingram MF, Zovanyi A, Heinrich M, Piper A, Zelko J, Olinger GG.Sci Transl Med. 2013 Aug 21;5(199):199ra113. doi: 10.1126/scitranslmed.3006608

MERS – a bioterrorist plot?

Two publications from Raina MacIntyre of the School of Public Health and Community Medicine, University of New South Wales[i] suggest that bioterrorism or accidental lab release could explain the origin of the MERS coronavirus. Is this a possibility? For me the answer is a very firm NO.

 

In essence the authors use standard epidemiology parameters to assess the pattern of MERS infections to date. The methodology is fine but the dataset used is not. The accepted problem for any modelling is the quality of the data used for the predictions, cynically termed the GIGO problem (garbage in, garbage out), a minor change in which can have a disproportionally big outcome. Think about the numbers that were predicted to have nvCJD (human BSE) or to die in the last influenza pandemic – both hugely overestimated early on in the epidemics. The issue with MERS is the dataset is small and much of it uncertain (the number of cases increased sharply following the change of Saudi health minister in June but these cases were mostly anecdotal as the patients are all dead. The precise details of the cases and technical proof of MERS infection are lacking). It is true that the exact origin and route to man is still unclear but there are no grounds to invoke bioterrorist or accidental release. For bioterrorism the virus clearly doesn’t work well in man so is hardly going to change the course of anything – it is a poorly transmitting virus so why would it be released? And who is it targeted at? Similarly, accidental release would require a local lab working on the virus or a very similar virus – none known, especially in the Middle East. In the latter case the epidemiology would also clearly trace back to the originating lab instead of being all over the place.

Death

 Pieter Bruegel’s “The Triumph of Death” is a favourite accompanying picture for bioterrorism texts. But is it a realistic scenario for the Middle Eastern Respiratory Syndrome coronavirus?   

The latest molecular studies show that the virus is able to infect camel, goat, cow, and sheep cells, which would fit the idea of a zoonotic origin (probably bats) that gets across to domestic livestock, likely as a silent infection that is not reported. Occasionally and via circuitous routes it gets to man where it can lead to severe respiratory distress, especially if the patient is already compromised in some way. The age and male predominance of cases to date fits with typical social roles that would interface with livestock. My own view is that low level contamination of food is also a possibility and the recent finding that the virus can survive for several days in unpasteurised milk shows this is a realistic possibility. Overall however the data are too fragmentary to offer a clear answer.

 

The papers from UNSW do not offer any direct evidence for a deliberate or accidental release of MERS-CoV. With our present state of knowledge you might as well drag up viruses from outer space (nonsense that was wrongly invoked to explain the SARS outbreak). It is none of these things. MERS CoV is a newly recognised and rare zoonotic infection whose pattern of spread will only become clear when more case controlled studies like those recently initiated by the new Saudi health minister have been completed. Science will get to the bottom of MERS, not speculation.


[i]

  1. MacIntyre CR. The discrepant epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV). Environment Systems and Decisions. Formerly The Environmentalist. 2014 10.1007/s10669-014-9506-5
  2. Gardner LM, MacIntyre CR. Unanswered questions about the Middle East respiratory syndrome coronavirus (MERS-CoV). BMC Res Notes. 2014 Jun 11;7:358. doi: 10.1186/1756-0500-7-358.

 

Ebola – why vaccines and drugs are not the answer

The Ebola outbreak in Western Africa continues to attract as lot of press coverage and a perfectly understandable response to the crisis is to ask why drugs and vaccines are not available. Vaccines are available for many virus infections and some are also treated successfully with drugs (your cold sore, caused by herpes simplex virus, for example), so why not for Ebola? Some scientists have been quite forthright in suggesting that experimental vaccines should be rolled out immediately on compassionate grounds (see bottom of article). This is unlikely to happen anytime soon for reasons that apply not only to Ebola but also to many other emerging infections.

For vaccines there are several points which make a roll-out unrealistic, at least in the short to medium term.

1)       The number of patients is too small. Who would make a vaccine to sell or donate so few doses? How would it be stored when not in use – it probably has a shelf life so any stockpile would have to be renewed regularly. Who would do that and for how long?

2)       How would you satisfy safety requirements? If the vaccine is experimental it will not have been trialled in a large population so the safety profile would be unclear. Would it be given to children? Or immunodeficient people? Who would bear the cost if there was an adverse event?

3)       The take-up may not be high. The current Ebola outbreak is characterised by fear and mistrust of foreign medical teams. Why would that be different for a vaccine? Even if available a vaccine may not reach the target population.

There are similar concerns experimental drugs.

1)       Almost all our successful antiviral drugs work against chronic not acute infections. The few that have been trialled for acute infection have mostly failed. The general consensus now on the use of anti-influenza drugs in the last pandemic is that they were largely useless (see article). It is not that the drugs don’t work, they do, but it is that they have to be given very early to have any effect and that in turn means rapid and accurate diagnosis. By the time the patient feels unwell it is too late so whether a drug could be given early enough to alter the clinical course of disease is currently unclear. Of course a drug could be given prophylactically to those at risk from patient contact but that would mean giving drugs to some individuals, including perhaps children, who may never actually become infected. Like the vaccine situation there is a risk of adverse events here and it is unclear who would bear that risk.

It is these issues that cloud the “compassionate grounds” argument and effectively hold back more forthright approaches. The other point is that a focus on treatment rather than prevention risks leading to a false sense of safety where practices such as consuming bushmeat continue – any treatment has to go hand in hand with education.

Ebola can be controlled by preventing transmission in the same way as a number of other zoonotic infections. To invoke vaccines and drugs tends to obscure this simple fact. Perhaps in the longer term as part of a regional emergency response system new and emerging therapies could play a role, but for now the traditional approach of contact tracing and barrier nursing has to be top of any list. Not everyone infected dies so convalescent serum collection could also be put in place.  Of course all of these things are useful but they all take time and will not be in place to impact the current outbreak.