Sunday July 12, 2009
What is an appropriate response?
By Dr MILTON LUM
The country’s response to the H1N1 pandemic has elicited many different opinions from the public as well as health professionals. A case of too little, or too much?
INFLUENZA epidemics, which occur annually, are widespread outbreaks of the infection in a community or region. A pandemic is different in that there is sustained human-to-human transmission of influenza with community outbreaks in at least one country in two World Health Organization (WHO) regions. It is no longer possible to contain the virus to a particular geographical area.
During previous pandemics, the influenza virus took more than six months to spread as widely as the influenza A (H1N1) took to spread in less than six weeks since the detection of the initial cases in Mexico and the United States. International travel has contributed very significantly to the spread of the virus, seeding urban areas prior to wider geographical spread within countries.
The Health Ministry’s response to the pandemic has become the subject of public debate. Some, including doctors, are of the view that the Ministry has over-reacted. Others are of the view that the measures are not stringent enough.
In addressing this debate, several factors are worthy of consideration.
Novel virus and correct terminology
The novel influenza A (H1N1) virus contain genes from human, pig (swine), and bird (avian) influenza A viruses, although it was initially thought to have originated in swine. Laboratory analyses by the Centre for Disease Control have shown that the influenza A (H1N1) virus have unique gene segments from four different viruses – some North American swine and avian viruses, one human virus and two Eurasian swine viruses.
The influenza A (H1N1) virus had not been identified before among human or swine influenza A viruses. That is one of the major reasons why WHO renamed it.
People have not got influenza A(H1N1) infection from eating properly handled and prepared pork or other pork derived products. The virus is killed by the commonly used cooking temperatures.
The impact of statements by those who influence public opinion cannot be underestimated. The wife of a specialist colleague, whom I met socially recently, opined that the problem can be solved by mass culling pigs. One can only imagine what public perception of the cause of this infection is when even those with tertiary education can be misled by ill-informed terminology from a governmental agency.
To substitute the term swine influenza for influenza A (H1N1) will not only lead to confusion but also create a false sense of security in those who do not consume or who are remote from swine. Furthermore, what term would be used for the influenza viruses that infect swine?
The influenza A(H1N1) virus is different from the ordinary seasonal influenza because it is a new virus that has appeared in humans. Since it a new virus, no one will have immunity to it and everyone is at risk of getting the infection. This includes healthy adults, pregnant women, older people, young children and those with existing medical conditions like diabetes, lung, kidney, liver and neurological disease.
The virus causes a spectrum of disease that range from mild upper respiratory tract illness, without fever, to severe or fatal pneumonia. Most cases appear to have uncomplicated, typical influenza-like illness and recover spontaneously. However, one third of those hospitalised in Mexico required ventilators to support their breathing.
Previous pandemics
Three influenza pandemics occurred in the 20th century. They were the Spanish flu which started in 1918, the Asian flu in 1957 and the Hong Kong flu in 1968, involving the H1N1, H2N2 and H3N2 subtypes respectively.
All the pandemics affected large population numbers, with considerable morbidity and mortality as well as social and economic impacts. The estimated deaths worldwide for the Spanish flu, Asian flu and Hong Kong flu were 50 million, one to two million and 700,000 respectively.
Even those in the United States were not spared, with 675,000, 70,000 and 34,000 deaths in 1918, 1957 and 1968 respectively.
All the previous influenza pandemics had certain characteristics, viz: a shift in the virus subtype, shifting of mortality to young people, multiple waves of infections, higher transmission rates than that of seasonal influenza, and variations in its impact in different geographic regions.
Whilst mortality occurred in those at the extremities of life or who those had medical conditions in seasonal epidemics, young people were also affected in the 20th century pandemics as shown in the chart for the 1918 pandemic.
The excess mortality from the pandemic virus can last up to five years after its first appearance. It is pertinent to note that many who died in the current pandemic are young people, just like in the 20th century pandemics.
All the pandemics in the 20th century were characterised by a series of multiple waves, each of which caused increased mortality for two to five years. There was a mild first wave during the summer in the 1918 pandemic, followed by two severe waves the following winter. The 1957 pandemic had three winter waves during the first five years. The 1968 pandemic had a mild first wave in Britain, followed by a severe second wave the following winter.
The transmission rates are higher in a pandemic as compared to the seasonal influenza.
This is because the population is more susceptible due to the change in the virus subtype to which they have not previously been exposed to.
The impact of the infection during a pandemic varies in different geographical regions of the world. The incidence and mortality varies considerably due to a complex interplay of several factors, which include the degree of immunity of the population to the circulating influenza subtypes and transmission factors like degree of infectiousness, extent of social interactions and geography.
Pandemic threats
There were also pandemic threats which included the Russian flu threat in 1977 and the avian flu threat in 1997. The Russian flu threat started in north China, involving children and young adults, and spread around the world. As children were the main group affected, it was not considered a true pandemic. A vaccine containing the virus subtype was not produced in time for the 1977-1978 flu season, but it was included in the 1978-1979 vaccine.
The avian flu threat occurred in 1997 to 1999. The influenza virus moved directly from chicken to humans. Many of those who were severely ill were young adults. The avian influenza virus did not spread easily from one person to another. With the culling of millions of chickens, there were few reports of new human infections.
The continued presence of avian influenza viruses in birds, their ability to infect humans, its ability to mutate and become more transmissible in humans is a continuing concern.
Unknowns and uncertainties
There is much that is unknown and uncertain about the influenza A (H1N1) infection as it is a new virus.
The clinical spectrum of disease caused by the new influenza A (H1N1) viral infection is wide and may evolve, especially when more of the vulnerable, e.g. pregnant women, those with asthma, malnutrition, chronic infections like HIV/AIDS and other medical conditions are infected.
One can only speculate on the spectrum of disease should the influenza A (H1N1) virus exchange genetic material with other human, swine or avian influenza viruses. The H5N1 avian influenza virus sub-type has already demonstrated its ability to infect people and cause severe disease with mortality rates of more than 50%. What would happen should there be human infections from a influenza virus subtype after exchange of genetic material between the H5N1 avian and the A (H1N1) viruses? No one knows!
There is limited evidence of the effectiveness of vaccination and antiviral medicines in the reduction of the health impact and the stopping and limitation of the spread of new influenza viruses. Vaccine development and mass production take six months or more after the virus subtype has been identified.
There is, however, current evidence to support the targeted use of vaccines, once it is available, and certain antiviral medicines, in priority groups and infected patients. The effectiveness of the vaccine may be limited by the evolution, or worse still, mutation, of the new virus.
The use of antiviral medicines is limited by its resistance to some prevailing influenza strains and cost.
Although the antiviral medicine, oseltamivir, has been shown to be helpful in the treatment of influenza A (H1N1), there are already reports of resistance to the medicine in Denmark, Japan and Hong Kong. These patients had to be treated with another antiviral medicine, zanamivir.
The possibility of higher doses, longer treatment regimens and increased costs of some other antiviral medicines is not only always present, but also likely to occur.
Containment and mitigation
Malaysia is currently at the containment phase. The longer we are at this phase, the better it is an indication that the spread of the infection is still controllable. In addition, time is being bought for a vaccine to be available.
Some countries have moved to the mitigation phase – e.g. the United Kingdom, which has the highest number of cases in Europe. There were 7,447 laboratory confirmed cases and three deaths as of July 3, 2009. It was reported that the British Health Secretary informed Parliament that, at the current rate of infectivity, there are projections of about 100,000 new cases daily by the end of August. The health authorities there have ceased attempts to control the spread of the infection, not because the infection is usually uncomplicated but because their resources could be better utilised by focusing on those who are susceptible.
The Chief Medical Officer, in an advisory on July 2, 2009, has advised doctors in the United Kingdom to make a diagnosis of influenza A (H1N1) infection by clinical diagnosis without taking swabs for laboratory confirmation unless there are special reasons for doing so.
Early antiviral treatment is to be prescribed for those above 65 years and up to five years, those with medical conditions, the immunosuppressed and pregnant women.
It has to be borne in mind that there are very few countries in the world that are as well prepared as the United Kingdom for an influenza pandemic as they already had stocks of antiviral medicines for more than half its population prior to the start of the pandemic and a robust healthcare delivery system as well.
Malaysia does not have the financial and human resources to mount a response on the same scale as the developed economies are doing when they move into the mitigation phase.
If Malaysia, with our limited resources, has to move into the mitigation phase, a possibility that appears to be increasingly more likely with each passing day, the issues will become much more complex and may be heartrending.
The debate then would not be about whether the measures taken are too much or too little. It could be about who will be treated and who will not, and if the intensive care units cannot cope with the number of patients admitted, who will live and who will die.
Conclusion
Whether the measures taken by the Health Ministry so far are too much or too little is a question that cannot be answered now or in a few months time.
Given the tricky influenza virus with its propensity to mutate and spread as is characteristic of a pandemic, the answer may be found in a few years time or so when the pandemic ceases or wanes.
The answer would be influenced considerably by the numbers from the initial and successive waves of illness and death caused by the influenza A (H1N1) virus.
It would also not be a definitive answer as the population has not been divided into two categories – one with containment measures and the other with mitigation measures – as it is unethical to do so.
Health policy makers have the unenviable and challenging task of addressing a combination of unknowns, uncertainties and urgency. Any intervention will involve trade-offs between the social and economic costs and the uncertain probability of greater harm of a widespread outbreak.
Dr Margaret Chan, the Director General of the World Health Organization, sums up this daily dilemma for health policy makers at the high level meeting on Influenza A (H1N1): Lessons learned and preparedness on July 2, 2009 at Cancun, Mexico:
“In keeping our populations informed, we face a difficult challenge. We cannot be alarmist, as this risks flooding emergency wards with the worried well, creating disruptively high demands for staff, hospitals, and laboratories. I am sure you will agree: health services need to stay fit for genuinely severe cases.
“At the same time, if we are overly reassuring, patients in genuine need of treatment, where rapid emergency care can make a life-and-death difference, may be lulled into waiting too long.”
While science, communications, health systems organisation and international collaboration should contain and control the infection, everyone has to play their respective roles for the measures to succeed. It is in everyone’s interest to put up with some inconveniences and adhere strictly to the health messages in the print and electronic media.
Individual efforts may not be significant by themselves but the collective contributions will be substantial.
The active participation of the public is crucial to controlling the spread of this new disease. Patience and understanding of the challenges for health policy makers is crucial as well as continued vigilance, but neither panic nor complacency should be allowed to come into the picture.
■ Dr Milton Lum is a member of the board of Medical Defence Malaysia. This article is not intended to replace, dictate or define evaluation by a qualified doctor. The views expressed do not represent that of any organisation the writer is associated with.
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