One Flu Over The Human Nest
by Lee Tse Ling
The Star Online > Health
Sunday March 5, 2006
One flu over the human nest
Vaccination is one of the greatest achievements of medicine and has spared millions of people the effects of devastating diseases. It’s clear it has a vital role to play in the ongoing concerns over the bird flu.
THAT the next influenza pandemic is on its way is not mere hyperbole. It’s a very real risk, with serious implications.
“We had three pandemics in the last century, and there is no reason to believe there won’t be one in this century,” Nature quoted Klaus Stohr, chief influenza expert of the World Health Organisation (WHO), in May 2005.
We are in our 39th year since the last pandemic outbreak, the longest period the world has gone between pandemics. And nobody can predict how long this window will last.
What sort of numbers are involved when we use the word “pandemic”? In a normal year, the WHO estimates between 5% and 15% of the world’s population is affected by influenza. That’s between 300 million and nearly a billion people. Out of this, up to one million die from influenza-associated complications.
According to Stohr, a severe pandemic-level attack (infection rate: 35%) could result in up to a billion people becoming ill, 28 million hospitalisations, and seven million deaths worldwide. Again, these figures are not hyperbole – the 1918 Spanish Flu attack rate approached 40% at its worst, claiming at least 20 million lives. The 1957 Asian Influenza and 1968 Hong Kong Influenza claimed another four million each.
The crucial difference between 1918 and 1957/1968, and indeed between what happened then and what may happen now, was and still is pandemic preparedness as individuals, as a nation and as a global community. And a crucial element of any preparedness plan will be an effective vaccination policy.
Flu virus 101
There are three types of influenza viruses: A, B and C. All three can infect humans.
While type B viruses have been known to cause epidemics, they have never caused pandemics. (Terminology/Definitions: If a disease is endemic, it is restricted or peculiar to a locality or region. An epidemic affects an abnormally large number of individuals within a population, community, or region at the same time. A pandemic occurs over an even wider geographic area [i.e. globally] and affects an exceptionally high proportion of the population.)
Type C viruses only cause mild illness in humans.
The high-pathogenic influenza A H5N1 infection on the other hand has a mortality rate of almost 100% in poultry, and 50% in humans. That is, it has killed almost every infected bird, and one in two infected humans.
Only type A viruses are classified into subtypes by the unique haemagglutinin and neuraminidase proteins found on their surfaces. These proteins are given identification numbers e.g. H1 and N5 and are used in combination to identify type A subtypes e.g. H1N1, H1N2 and H3N2 – the A subtypes in common circulation amongst humans.
All are further classified into strains. Strains develop due to gradual genetic changes. This process is known as antigenic drift – where many small changes accumulate over time e.g. random mutations that occur in a virus particle’s RNA, making its surface proteins less recognisable to the immune system.
Think of it this way: it’s as if a friend of yours gradually grew a moustache and beard. They haven’t changed that much, but you might not recognise them initially over time. And what the immune system can’t recognise quickly, it can’t kill quickly.
Sudden change generates new subtypes through a process known as antigenic shift – where the virus particle acquires a surface protein combination that has not been seen in humans before, or not been seen for a long time.
Because our immune systems have never encountered such a foe, everyone – not just people with young or compromised immune systems – will be susceptible to infection. Think of it this way: it’s as if your friend has gone for drastic plastic surgery now. They’ve changed completely and you can’t recognise them at all. And what the immune system can’t recognise at all, it can’t kill, period. This is what a high-pathogenic H5N1 virus capable of infecting humans will be like.
Several facts make it difficult to eradicate type A viruses. To begin with, they are naturally resident in wild bird populations, which spread them across the globe during their annual migrations. Not only are they persistent in the environment, they are also capable of lying “silent” and can therefore spread undetected in domestic ducks. Lastly, they undergo both shift and drift – producing a source of new and infectious strains and subtypes.
For the moment, the virus does not spread easily from birds to humans. This becomes obvious when you compare the very large number of domestic birds exposed to H5N1 (more than 150 million culled so far), their close proximity to humans, especially in village communities with backyard flocks, to the small number of humans who have contracted the disease from them (approximately 100). Furthermore, the outbreaks of H5N1 have only occurred in small clusters, indicating that it is not easily transmitted from human to human.
Vaccines
In the face of this, vaccines will play a two-fold role in keeping a pandemic in check. The obvious solution is a vaccine that confers protection against human H5N1. However, it will be some time before this new vaccine will make it from the producers to the rest of the world.
In the first place, until H5N1 begins infecting humans in earnest, it is unlikely a highly effective formulation can be developed. That’s because in order to get past our immune systems, the virus will have to evolve a completely novel trait, one our current vaccines have not forewarned our systems about and primed them against.
In the second, vaccine distribution will be limited by production capacity and locality. The vaccine industry is one that never manages to meet demand. World production capacity is currently 300 million doses per annum. That is, enough doses to vaccinate just 5% of the world’s population. Compare that with the postulated attack rate of 35%.
Furthermore, most of the world supply of influenza vaccine is produced in Europe and the US. A small amount is manufactured in Japan. Asia is almost exclusively dependent on Europe for its vaccine supply. It is a tricky situation US vaccination and public policy expert Dr David Fedson brought up in an interview with the Asia-Pacific Advisory Committee on Influenza (APACI).
“We still need to deal with the political implications of distributing pandemic vaccine to countries that do not have production companies of their own. It is likely that the political leaders of countries in which vaccine companies are located will nationalise the production of pandemic vaccine, preventing export until all of their citizens have been vaccinated,” he said.
According to the National Influenza Pandemic Preparedness Plan (NIPPP), it is unlikely Malaysia will receive the H5N1 vaccine until at least six months after large-scale production begins. What can be done in the meantime?
The rationale for vaccination
The best thing we can do to slow the pandemic is to limit the chances of antigenic shift happening. The chances of this happening are high when two influenza viruses – e.g. the high-pathogenic H5N1 bird flu and any human flu virus – infect a human at the same time.
Once in this “mixing vessel”, the viruses can genetically re-assort. That is, they can trade packets of genetic information. What you don’t want the human flu virus to pass on to the H5N1 bird flu virus is a manual titled How to Infect Humans. So first things first – vaccinate the normal hosts: poultry. Second, vaccinate the mixing vessels: humans.
“A strategy to bar the meeting of the viruses in the human body would go a long way towards preventing the emergence of a deadly new virus. It would reduce the opportunities for simultaneous infection of humans with the avian and human flu viruses, decreasing opportunities for reassortment. I believe this can be achieved with higher immunisation rates with the influenza vaccine,” says consultant paediatrician and neonatologist Dr Musa Mohd Nordin.
Besides slowing the evolution of such a virus, increased vaccination will encourage the growth of vaccine production capacity and vaccination infrastructure.
“Perhaps the best we can hope for is to develop the global capacity to produce as many doses as possible, so that they can be supplied to non-producer countries sooner rather than later,” said Fedson in the same APACI interview.
“Too much attention has been focused on curative strategies. My back-to-basics virology and vaccinology would suggest that during this inter-pandemic period, influenza immunisation would be the best option for protection against influenza and would help to mitigate the emergence of a pandemic virus. This investment would prove to be a cost-saving policy. It would undoubtedly decrease the health burden of annual influenza flu epidemics and prevent influenza morbidities and mortalities,” says Dr Musa.
He adds: “Quite evidently, the pandemic clock is ticking; we just do not know what time it is!”
A guide to vaccination
CHILDREN
Consultant paediatrician and neonatologist Dr Musa Mohd Nordin recommends the influenza vaccination for all children, in particular those above the age of six months and below nine years.
Past six months, the immune system is mature enough to make protective antibodies. But at that young age, the child is still vulnerable to infection, as his/her immune system may not be experienced enough to cope with an attack.
High priority groups include those with:
# Pulmonary conditions e.g. asthma, chronic lung disease of immaturity
# Heart conditions e.g. congenital heart disease
# Kidney dysfunction
# Blood disorders e.g. thalassaemia
# Metabolic disease e.g. diabetes
# Compromised immune systems, including those with HIV infections
The vaccine should not be administered if the child:
# Is under six months of age
# Has a known allergy to eggs, chicken proteins, neomycin (an antibiotic) and other active substances in the vaccine e.g. formaldehyde
# Has had an adverse reaction to the vaccine in the past
# Has a fever or is experiencing an acute illness (in which case, simply postpone the vaccination)
Dosages
# Children aged between six months and 35 months should receive a half-dose (0.25ml)
# Children aged three years and above should receive a full-dose (0.5ml)
# Children below nine years who have not previously received the vaccination should be given a second booster dose one month after the first
# Children above nine years should receive an annual dose
ADULTS
In general, anyone who wants to reduce their chances of contracting influenza should get vaccinated annually. However, high-priority groups include:
# People living in nursing homes and long-term care facilities
# People with the chronic conditions listed under high-priority for children
# People with impaired respiratory function (those conditions that make it difficult to breath or swallow e.g. brain or spinal cord injuries; seizure disorders; and nerve or muscle disorders)
# Women who will be pregnant during the influenza season
# Anyone who can transmit influenza to others in high-priority groups e.g. healthcare workers and caregivers
THE ELDERLY
The elderly typically have weaker immune systems and may experience chronic diseases that render them more susceptible to infection and complications following infection. Consultant geriatrician Dr. Rajbans Singh recommends annual influenza vaccination for all persons above 60.
“Patients who have taken their influenza and pneumococcal vaccines have less incidence of chest infections. I also find the vaccine safe with no side effects,” he says.
The vaccine should not be administered if the elderly persons in question:
# Has a known allergy to eggs, chicken proteins, neomycin (an antibiotic) and other active substances in the vaccine e.g. formaldehyde
# Has had an adverse reaction to the vaccine in the past
# Is febrile
# Is immunocompromised
Note: Information compiled from the US Centre for Disease Control (CDC), vaccine manufacturer Sanofi-Pasteur and local specialists.
Dispelling myths about influenza vaccination
Myth #1: The common cold is the same as influenza
According to consultant paediatrician and neonatologist Dr Musa Mohd Nordin, influenza is often erroneously equated with the common cold.
“Hence the myth that it is a relatively mild illness which improves rapidly over two to three days, and that lots of rest, fluids, vitamin C and aspirin are all that is required. On the contrary, they have strikingly different pathologies (i.e. collection of abnormalities). Influenza is often associated with high-grade fever lasting three to four days; severe muscle aches, chest discomfort, early and severe physical weakness and generalised fatigue, which could last up to three weeks,” he says.
The two are both respiratory illnesses caused by different viruses. Anyone who has experienced a bad attack of viral influenza will know the difference. If you haven’t, have a look at the accompanying table, Flu or cold?
Myth #2: The current influenza vaccine will protect you from bird flu
When medical practitioners recommend vaccination as the primary means of preventing influenza, they’re referring to the normal influenza vaccine – meaning, the influenza you are being vaccinated against is not the H5N1 subtype, but the endemic subtypes that normally circulate and cause the seasonal epidemics we are familiar with.
It is unlikely the current vaccine formulation will confer any cross-protection against a virulent H5N1 subtype. By definition, a pandemic can only occur when a new subtype emerges or when a subtype has disappeared over many generations re-emerges.
Myth #3: The influenza vaccine only protects me
Herd immunity, or community immunity arises when enough individuals in a population are protected from a given infection. Since nobody catches the infection, nobody spreads it, so the infectious agent never has a chance to get a foothold. While a few vaccinations may protect individuals, widespread vaccination protects everyone. This is how smallpox was eradicated completely by 1980.
Myth #4: The influenza vaccination is only for travel
Current data shows the influenza vaccine is an effective, vital and common pre-travel protective measure. Vaccination rates among Malaysians as a whole are low – about one in every four hundred people (0.3%).
On the other hand, vaccination rates among travellers are high – a 2000 study on vaccine effectiveness in Malaysian Haj pilgrims showed a rate of up to 88%. That’s nearly every nine out of 10 people, thanks to the constant recommendations made by the Haj Authority.
The study also showed that the influenza vaccine was 78% effective in protecting recipients from clinic visits for influenza-like-illness. Why stop there? School environments, offices, and public transport all are environments in which influenza can be transmitted too.