H1N1: Contagion escalates, but caution still advocated...

Part of this article appeared in The Star 01 July 2009 as Caution can Save Lives and in Malaysiakini as Better Safe than Sorry on 30 June 2009.

Last Wednesday 24 June 2009, I attended the National Influenza Pandemic Task Force meeting chaired by the DG of Health, Tan Sri Dr Ismail Merican.

There remains fear that the H1N1 flu infection will continue to spread in the country, with most being imported cases, but with a steadily growing person to person spread becoming a reality. The plan is to try and contain and limit the contagion to as few people as possible and thus perhaps shield Malaysians from the worst aspects of this pandemic's potential lethality and socioeconomic perils.

As of June 26, the latest WHO statistics show that of 59,814 reported cases there have been 263 deaths — a mortality rate of 0.44%.

This is in contrast to two other high-profile global health threats of recent years. Avian Flu (influenza A(H5N1) had 433 reported cases and 262 deaths; while SARS (Severe Acute Respiratory Syndrome) had 8,096 reported cases and 774 deaths; thus their mortality rates are much higher at 61% and 9.6% respectively.

(Contrast this with our resurgent dengue fever; in the first half of this year, there were 23,057 dengue cases and 57 related deaths in Malaysia, i.e. 1 death in 404 cases or a case fatality of 0.25%.)

Not Really Much Ado about Nothing
Although some skeptics had brought up concerns that perhaps the response to this current pandemic is overblown or exaggerated, and that socio-economic implications remain still unrealised; the MOH and the DG pointed out correctly that while this may turn out to be true in the longer term, we just can't simply sit by and let this pandemic go without careful monitoring.

One very important and poignant point raised by the DG is that, if and when this pandemic turns out to be truly benign, then it's well and good. But consider the converse, if this flu became more lethal and many Malaysians then die, what then? Will the culpability for this potential disaster be equally shared for blame and recriminations? Indeed, will anyone then wish to take the rap, the responsibility?

In neighbouring Thailand, as of today, two among the hundreds infected have died, so this is not so benign after all. In the USA, CDC spokesperson, respiratory director Dr Ann Shuchart has stated that perhaps as many as 1 million Americans may have been infected with the H1N1 virus.

U.S. Passes Million Swine Flu Cases, Officials Say

Of the 27,717 laboratory-confirmed cases, about 3,000 Americans have been hospitalized, (their median age was quite young, just 19) and 127 have died; i.e. an in-hospital case fatality rate of 1 in 23, or 4.2%. Those who have died had a higher median age of 37 years, and when looked at in this way the actual in-hospital case fatality rate is around 2%.

But if we were to consider that the true number is perhaps just half as estimated, then 127 out of 500,000 exposed, is about as benign as the usual seasonal flu... Even if we considered just lab-confirmed cases, the case fatality rate would have been 0.45% or 1 in 218, very consistent with global figures.

Still, Malaysians are known to be very quick at pointing fingers and apportioning blame and vindictive censure. Many very vocal citizens are frequently irrationally strident and unforgiving, expecting that no authority or government can do any wrong!

Already there have been mutterings that we have not done enough. A recent letter No wonder A (H1N1) cases are on the rise stated that Singapore's surveillance methods are better and more visible, just because that person and their friends were not screened when crossing over the 2nd Tuas Link into Johor Bahru when returning. Yet they fail to note that the tiny nation state has already more than twice the number of cases of H1N1 infections than Malaysia, with even greater numbers of local transmission! Sadly, it's that inherent color of bias that our neighbour down south is always perceptibly better, whatever the raw unvarnished truth!

Hence, Malaysian health authorities have very limited options. Rigorous vigilance, close monitoring and being overly cautious might be the more prudent approach—yes, perhaps, this might cost us a bit of time, energy, resources and money in the beginning, but in the long term this would have been worth it—every life saved, is and should always be a correct public health measure! The question that begs to be answered is, at what cost?

It is true that many countries are loosening their surveillance programmes and are moving towards mitigation measures, which will help preserve resources and perhaps offer a more realistic approach to the pandemic.

Of course, everyone hopes that this flu will peter out after the initial wave of snuffles and fever subsides, if or when it does. But much remains to be seen, the unknowable remains as unpredictable as ever, and the possible future scenarios range from the most optimistically benign to the most catastrophic!

In the meantime, we can only help by assisting the MOH to respect and abide by the continually updated measures that are being rolled out on a day-to-day basis. At the very least, we can help by mitigating against the careless spread of this quite contagious virus, by scrupulous hygiene measures, and where necessary, by applying strict self-quarantine, if and when, anyone of us, might be possibly infected. Let's do our civic duty and be responsible and good citizens!

Fears of ‘second wave’ bug may be exaggerated

JUNE 27 — A new strain of the pandemic virus was identified in Shanghai in the middle of this month.

This, however, was reported by the media in mainland China only. The virus isolated from a 22-year-old Shanghai woman shows a significant mutation called E627K in the PB2 gene, one of the novel strain’s eight genes.

(A recent MIT study shows that without the PB2 gene, human viruses spread mainly by contact. Acquisition of the avian PB2 gene, however, enables them to transmit by air, which is why the pandemic strain is spreading so rapidly now.)

Before E627K appeared in the PB2 gene, PB2 was simply that which the pandemic strain had acquired from bird viruses. When E627K appeared, however, it meant that the PB2 gene was humanised or better adapted to people.

These genomic details can be confirmed on two free Internet databases. The expert who first noticed the E627K mutation in the Shanghai isolate noted that, in 1997, the H5N1 bird flu virus seen in Hong Kong which was very virulent in lab mice also carried E627K.

Dr Henry Niman of Pittsburgh-based Recombinomics, a private consultancy, told The Straits Times that, in 2003, the H7N7 bird flu virus that killed a veterinarian in the Netherlands had E627K as well.

Most importantly, the world’s only sample of the 1918 pandemic virus ever isolated from a patient also has E627K. This victim had been buried in Alaska (in permafrost) in November 1918 when the bug was killing people ferociously.

The Shanghai sample also shows another significant mutation, D701N, which is thought to augment E627K’s ability to infect humans. Does this Shanghai strain, which the United States authorities have now noted with little fanfare, presage a lethal second wave later this year?

It seems ominous. East Asia is ground zero for all flu virus mutations, a fact confirmed last month by two genomic studies. From Asia, mutated flu viruses are then spread by humans via air travel to both hemispheres. So E627K being detected in Shanghai first looks bad.

However, other experts remain sceptical: Whether the bug already had E627K in the spring and summer of 1918 when far fewer deaths were noted is not known. This is because there isn’t a single patient sample from that spring or summer to compare with the sole autumnal one available. Thus, one cannot conclude that it was E627K that turned the bug ferocious.

All that can be deduced is that E627K is associated with, not causal of, virulence. Likewise, E627K was also only associated with but not proven to cause the virulence in the 2003 Dutch case or the 1997 Hong Kong sample.

Until E627K is widely detected in a lethal second or third wave of the current pandemic, its relationship to virulence remains conjectural. More generally, the 1918 pandemic per se offers no genomic evidence that it was mutations after a mild spring or summer outbreak that caused the bug to turn ferocious.

Say, mutations were not responsible. What then might have caused the virulence in 1918? Perhaps, the poor nutritional status of all during wartime was crucial. At any rate, with no antibiotics available in that time period as yet, most deaths in 1918 were caused by untreated bacterial pneumonias in people already laid low by the flu. There were probably lots of pneumonia-causing bacteria like pneumococci, staphylococci or Haemophilus circulating in the poor hygiene.

Then there were also killers like tuberculosis, cholera and typhoid as well as other non-flu respiratory viruses which might have presented with flu-like illness but remained undiagnosed.

Some scientists now speculate that the use of high doses of aspirin advocated then might have been responsible too. Aspirin can cause Reye’s syndrome – a situation in which there is potentially fatal brain and liver swelling in children with viral infections. While aspirin is therefore avoided in childhood fevers nowadays, there are many aspirin derivatives.

In Mexico, such derivatives as diclofenac, mefenamic acid and ibuprofen are easily available. Not knowing that these are related to aspirin, parents tend to use them for fevers in children when paracetamol (branded Panadol here) fails to work. These may potentially have the same harmful effects. Did this cause Mexico’s high kill rates this year?

Here is an even more radical idea. Perhaps the bug never turned ferocious in the autumn of 1918 at all. Some experts are now arguing that, without lab confirmation of cause of death, the estimated number of deaths attributed to flu in late 1918 is imprecise. (The virus was first identified only in 1933.)

In fact, the idea of a “lethal second wave” came from a Journal of Infectious Diseases study published in January last year. However, this is merely one study using highly imprecise data from 1918 in but one city, Copenhagen. Amazingly, these experts say, this study alone has given rise to concerns about a lethal second wave, which may be less relevant today.

There are now antivirals and ventilators to treat bad flu cases; antibiotics for bacterial pneumonias; flu vaccines and personal protective equipment to prevent infection; better nutrition and sanitation; and, the public is better informed too.

The future may not be so bleak, after all. (Andy Ho – Straits Times, Singapore)