What three infections should be prioritised for vaccine development and why? This is the question that the World Health Organisation has had to answer in the last few weeks. It may seem simple and you may have your top three but I wonder if you agree with the WHO.
So what did the WHO decide were their priorities?
The WHO has a published list of Top 5 diseases likely to cause an epidemic in the near future. These were agreed by a panel of experts in 2015 and include:
So what did the WHO decide were their priorities?
The WHO has a published list of Top 5 diseases likely to cause an epidemic in the near future. These were agreed by a panel of experts in 2015 and include:
- Crimean Congo haemorrhagic fever, Ebola virus disease and Marburg
- Lassa fever
- Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome coronavirus diseases
- Nipah
- Rift Valley fever
Okay, this is a bit of a cheat as those of you who can count noticed more than 5. There are actually eight diseases not five as the WHO says, but they justify the numerical error by putting similar infections, like the viral haemorrhagic fevers, together. Then they short list to just 3…
So the WHO is prioritising:
My initial reaction to the choices of the WHO was one of surprise. I couldn’t understand why they had chosen the infections they had. But then I started to think it through a bit more and the more I thought the more I realised I really didn’t know enough to judge the choices made by the WHO, I needed more information. Clearly I wasn’t one of their panel of experts!!
So how would I go about choosing three infections to prioritise for vaccination development? In order to answer this I would have to ask myself a number of questions:
1. What is the aim of vaccination?
Vaccination aims to prevent an individual not only developing a specific infection but also prevent them carrying the causative microorganism, therefore interrupting transmission of infection within a population. “Herd immunity” is a term used to describe when enough individuals in a population are immune that the specific cause of an infection is no longer able to spread from individual-to-individual and therefore anyone not immune does not come in to contact with the microorganism. Herd immunity only applies to infections spread from person-to-person (e.g. pertussis where vaccinating pregnant mothers and children protects new-born babies) not from the environment-to-person (e.g. tetanus from environmental spores or bacteria) in which case the individuals immunity protects them; an infected person poses no threat to others, it is the environmental source that poses the threat.
2. How severe is the infection?
Some infections are so severe that prevention is always preferable to treatment. Examples from the UK primary course of vaccination include diphtheria, tetanus, Haemophilus influenzae type b (Hib), Neisseria meningitidis types B and C (Men B and C) and measles. Not all of these are easy to spread but the infections are particularly nasty e.g. Hib and epiglottitis, Men B and meningitis.
Perhaps less obvious causes of “severe” disease are dependent on the situation in which they occur. Gastroenteritis in a country like the UK with freely available safe drinking water and good facilities for sewerage disposal are of less “severity”. However in developing countries gastroenteritis is a leading cause of death; exposure to infection from inadequately treated sewerage and an inability to keep patients hydrated because of a lack of freely available safe drinking water. In these cases severity is more of a “social” problem than a specific infectious one. Examples of these types of infections include: Enterotoxigenic E. coli, Rotavirus, Norovirus.
3. What is the economic burden of the infection?
As a Microbiology Registrar I was once asked what the most economically disastrous infectious diseases were and I naively said things like Human Immunodeficiency Virus (HIV) and Malaria as they stopped people in the developing world from reaching their full potential. My teacher Alan (then Senior Virology BMS in Nottingham) agreed that these were important but explained to me that the most economically disastrous infections did not affect humans at all. I feel I was set up for the fall! Alan gave the example of Foot and Mouth in the UK which caused a massive impact on the farming economy and rural areas of the UK; he also talked about Rinderpest in the past affecting cattle in places like Africa and preventing economic export of cattle. Clearly, politically I had more to learn!
Okay, I’m not talking here about what animal infections to prevent, so why is this important!? What is my point?! Well the most economically damaging infections are often not the most severe but can be the ones which have resources “spent” on them. In the UK gastroenteritis and upper respiratory tract diseases in children are probably the most economically damaging infections as they are very common and parents have to stay at home to look after their children when they are unwell. This takes the parents out of the workforce and businesses lose millions of “work days” a year to what are usually self-limiting infections. This economic argument was used to justify the introduction of rotavirus vaccine in to many European countries including the UK i.e. it was economically justified not medically justified. Some vaccinations are developed to save us money!
4. How easy does the infection spread person-to-person?
In my opinion there is less need to prevent infections caused by a microorganism that either does not spread from person-to-person or which inefficiently spreads from person-to-person. These types of infections have much less potential to cause outbreaks, epidemics or pandemics.
I would want to concentrate my priorities on those microorganisms which are highly infectious and which once introduced into a population will spread rapidly to infect many others. I would be especially concerned about infections which have a prodromal period in which the infected person is infectious to others before they develop symptoms, as these people will be able to travel (e.g. internationally by aeroplane) whilst infectious and rapidly disseminate the infection. Some of the current vaccine preventable diseases in the UK fit this type of infection e.g. measles, diphtheria.
5. Is there an effective treatment already?
The availability of an effective treatment to a particular infection is not necessarily a major argument against vaccination but it can make some infections less urgent than others. If an infection can be easily treated then it is less urgent to prevent it than if there is no effective treatment. Viruses are often difficult to treat and there are very few specific anti-viral treatments available therefore many of the viruses might be attractive to prevention.
Of course there are some infections which whilst they can be treated the infection is so aggressive that patients often come to harm before treatment can be given, e.g. Hib epiglottitis and Men B meningitis, which can be so overwhelming that the patient dies before reaching hospital; in which case prevention is better than treatment!
6. Are humans the only reservoir?
Whilst this would not be the highest priority for me I would at least consider it. If humans are the only reservoir for a particular microorganism then there is the potential to eradicate the infection through vaccination. This is what was done with smallpox and what is being attempted with polio.
So what would I choose as priorities?
My priorities for vaccination based on my considerations above would be:
So why does my list differ from the WHO’s list? That’s because there is another question to ask.
7. Is there already a vaccine or one in development?!
Sneaky question!!! The other issue to consider when deciding where to prioritise vaccine development is that there is little point pushing researchers and companies to develop vaccines where effective vaccines already exist or where they are already in clinical trials and will soon be available. In this case it would be better to target specific infections that don’t yet have anyone trying to deal with them.
The list below are the vaccines currently in development, as you can see my priorities are under development:
Once this list of vaccines in development is taken into account it becomes clear that my list of vaccines to prioritise do not actually need prioritising. Oh well…
So have the WHO got it right?
Lassa, MERS and Nipah are all viral infections which are easy to spread and have the potential to cause severe illnesses in humans. They are all highly contagious (either person-to-person or animal-to-person) and either have a prodromal period during which they can be spread or can be asymptomatic in some patients allowing them to spread the infections further, including worldwide. None of these infections currently have specific treatments and therefore in the circumstances of an epidemic, patients with the severe illnesses will rapidly overwhelm the intensive care facilities required to provide support to infected individuals. And finally, other than Nipah, there are no vaccines in the pipeline so if an epidemic were to occur there would be little that could be done to prevent them spreading.
So I have had to revise my initial assessment of the WHO choice of priorities for vaccination and actually I think they are spot on… but then THEY are the experts! Do you think the WHO are right? What would you choose?
So the WHO is prioritising:
- Lassa fever
- Middle East Respiratory Syndrome
- Nipah
My initial reaction to the choices of the WHO was one of surprise. I couldn’t understand why they had chosen the infections they had. But then I started to think it through a bit more and the more I thought the more I realised I really didn’t know enough to judge the choices made by the WHO, I needed more information. Clearly I wasn’t one of their panel of experts!!
So how would I go about choosing three infections to prioritise for vaccination development? In order to answer this I would have to ask myself a number of questions:
1. What is the aim of vaccination?
Vaccination aims to prevent an individual not only developing a specific infection but also prevent them carrying the causative microorganism, therefore interrupting transmission of infection within a population. “Herd immunity” is a term used to describe when enough individuals in a population are immune that the specific cause of an infection is no longer able to spread from individual-to-individual and therefore anyone not immune does not come in to contact with the microorganism. Herd immunity only applies to infections spread from person-to-person (e.g. pertussis where vaccinating pregnant mothers and children protects new-born babies) not from the environment-to-person (e.g. tetanus from environmental spores or bacteria) in which case the individuals immunity protects them; an infected person poses no threat to others, it is the environmental source that poses the threat.
2. How severe is the infection?
Some infections are so severe that prevention is always preferable to treatment. Examples from the UK primary course of vaccination include diphtheria, tetanus, Haemophilus influenzae type b (Hib), Neisseria meningitidis types B and C (Men B and C) and measles. Not all of these are easy to spread but the infections are particularly nasty e.g. Hib and epiglottitis, Men B and meningitis.
Perhaps less obvious causes of “severe” disease are dependent on the situation in which they occur. Gastroenteritis in a country like the UK with freely available safe drinking water and good facilities for sewerage disposal are of less “severity”. However in developing countries gastroenteritis is a leading cause of death; exposure to infection from inadequately treated sewerage and an inability to keep patients hydrated because of a lack of freely available safe drinking water. In these cases severity is more of a “social” problem than a specific infectious one. Examples of these types of infections include: Enterotoxigenic E. coli, Rotavirus, Norovirus.
3. What is the economic burden of the infection?
As a Microbiology Registrar I was once asked what the most economically disastrous infectious diseases were and I naively said things like Human Immunodeficiency Virus (HIV) and Malaria as they stopped people in the developing world from reaching their full potential. My teacher Alan (then Senior Virology BMS in Nottingham) agreed that these were important but explained to me that the most economically disastrous infections did not affect humans at all. I feel I was set up for the fall! Alan gave the example of Foot and Mouth in the UK which caused a massive impact on the farming economy and rural areas of the UK; he also talked about Rinderpest in the past affecting cattle in places like Africa and preventing economic export of cattle. Clearly, politically I had more to learn!
Okay, I’m not talking here about what animal infections to prevent, so why is this important!? What is my point?! Well the most economically damaging infections are often not the most severe but can be the ones which have resources “spent” on them. In the UK gastroenteritis and upper respiratory tract diseases in children are probably the most economically damaging infections as they are very common and parents have to stay at home to look after their children when they are unwell. This takes the parents out of the workforce and businesses lose millions of “work days” a year to what are usually self-limiting infections. This economic argument was used to justify the introduction of rotavirus vaccine in to many European countries including the UK i.e. it was economically justified not medically justified. Some vaccinations are developed to save us money!
4. How easy does the infection spread person-to-person?
In my opinion there is less need to prevent infections caused by a microorganism that either does not spread from person-to-person or which inefficiently spreads from person-to-person. These types of infections have much less potential to cause outbreaks, epidemics or pandemics.
I would want to concentrate my priorities on those microorganisms which are highly infectious and which once introduced into a population will spread rapidly to infect many others. I would be especially concerned about infections which have a prodromal period in which the infected person is infectious to others before they develop symptoms, as these people will be able to travel (e.g. internationally by aeroplane) whilst infectious and rapidly disseminate the infection. Some of the current vaccine preventable diseases in the UK fit this type of infection e.g. measles, diphtheria.
5. Is there an effective treatment already?
The availability of an effective treatment to a particular infection is not necessarily a major argument against vaccination but it can make some infections less urgent than others. If an infection can be easily treated then it is less urgent to prevent it than if there is no effective treatment. Viruses are often difficult to treat and there are very few specific anti-viral treatments available therefore many of the viruses might be attractive to prevention.
Of course there are some infections which whilst they can be treated the infection is so aggressive that patients often come to harm before treatment can be given, e.g. Hib epiglottitis and Men B meningitis, which can be so overwhelming that the patient dies before reaching hospital; in which case prevention is better than treatment!
6. Are humans the only reservoir?
Whilst this would not be the highest priority for me I would at least consider it. If humans are the only reservoir for a particular microorganism then there is the potential to eradicate the infection through vaccination. This is what was done with smallpox and what is being attempted with polio.
So what would I choose as priorities?
My priorities for vaccination based on my considerations above would be:
- Malaria – this is a global killer, responsible for millions of infections around the world every year and where an effective vaccine would prevent 100s of thousands of deaths a year as well
- HIV – according to the WHO HIV is responsible for 1.5 million deaths a year around the world and the lack of widely available treatments in the countries that need them the most means that a vaccine to prevent infection in the first place could protect millions of people
- Norovirus – gastrointestinal infections kill many people in developing countries but Norovirus has the added effect of causing large outbreaks in the developed world as well, and therefore there are both medical and economic reasons for wanting this infection prevented (and anyone who has had to close hospital beds over the winter because of Norovirus will probably agree!)
So why does my list differ from the WHO’s list? That’s because there is another question to ask.
7. Is there already a vaccine or one in development?!
Sneaky question!!! The other issue to consider when deciding where to prioritise vaccine development is that there is little point pushing researchers and companies to develop vaccines where effective vaccines already exist or where they are already in clinical trials and will soon be available. In this case it would be better to target specific infections that don’t yet have anyone trying to deal with them.
The list below are the vaccines currently in development, as you can see my priorities are under development:
- Campylobacter jejuni
- Chagas Disease
- Chikungunya
- Dengue
- Enterotoxigenic Escherichia coli
- Enterovirus 71 (EV71)
- Group B Streptococcus (GBS)
- Herpes Simplex Virus
- HIV-1
- Human Hookworm Disease
- Leishmaniasis Disease
- Malaria
- Nipah Virus
- Nontyphoidal Salmonella Disease
- Norovirus
- Paratyphoid fever
- Respiratory Syncytial Virus (RSV)
- Schistosomiasis Disease
- Shigella
- Staphylococcus aureus
- Streptococcus pneumoniae
- Streptococcus pyogenes
- Tuberculosis
- Universal Influenza Vaccine
Once this list of vaccines in development is taken into account it becomes clear that my list of vaccines to prioritise do not actually need prioritising. Oh well…
So have the WHO got it right?
Lassa, MERS and Nipah are all viral infections which are easy to spread and have the potential to cause severe illnesses in humans. They are all highly contagious (either person-to-person or animal-to-person) and either have a prodromal period during which they can be spread or can be asymptomatic in some patients allowing them to spread the infections further, including worldwide. None of these infections currently have specific treatments and therefore in the circumstances of an epidemic, patients with the severe illnesses will rapidly overwhelm the intensive care facilities required to provide support to infected individuals. And finally, other than Nipah, there are no vaccines in the pipeline so if an epidemic were to occur there would be little that could be done to prevent them spreading.
So I have had to revise my initial assessment of the WHO choice of priorities for vaccination and actually I think they are spot on… but then THEY are the experts! Do you think the WHO are right? What would you choose?
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