N. Gopal Raj

Experts have advised the WHO to continue using geographical spread as the basis to move a pandemic to Phase 6. But they have also indicated that it should modify the criterion to include an assessmentof severity.

With the swine-origin flu virus being reported from over 60 countries, the World Health Organisation is edging closer to announcing a full pandemic alert. The WHO’s global flu pandemic alert system is based on the geographical spread of the disease. But in response to concerns raised by a number of countries, it is planning to include an index of severity to declare that a pandemic is indeed under way.

After a novel Influenza A(H1N1) virus that originated in pigs was isolated from the sick in Mexico and the neighbouring U.S., the WHO raised its six-point pandemic alert status to Phase 4 on April 27. Three days later, it raised the international alert to Phase 5 after finding evidence of community-level transmission in both Mexico and the U.S. According to the WHO’s current criterion, evidence of community-level transmission of a virus in a country in another part of the world is needed to move to Phase 6 — the declaration of a pandemic.

“Globally, we believe we are at Phase 5 but are getting closer to Phase 6,” said WHO Assistant Director-General Keiji Fukuda at a recent press briefing. The virus was well-established in countries in North America and was spreading internationally. A number of countries such as the U.K. and Spain in Europe, Japan in Asia, Chile in South America and Australia appeared to be in transition, moving from travel-related cases to a more community-based spread of the disease. “However, we are still waiting for evidence of really widespread community activity in these countries,” said Dr. Fukuda.

During last month’s World Health Assembly in Geneva, the annual meeting of the WHO’s 139 member-states and the organisation’s supreme decision-making body, several countries took the stand that a pandemic alert must also take into account the severity of a disease. The WHO’s pandemic alert status was created to cope with the H5N1 bird flu, which killed 60 per cent of the people it infected. By contrast, the swine-origin flu virus has so far been much more benign, with most cases being relatively mild.

Over the last several days, the WHO has held discussions with experts from 23 countries on the pandemic phases and the severity of illness, Dr. Fukuda told reporters. They had advised the WHO to continue using geographical spread as the basis to move a pandemic to Phase 6.

However, they indicated that the WHO should modify this kind of shift with an assessment of severity. In doing so, the WHO should provide more tailored guidance to countries to help them respond better to the degree of severity, he added.

Consequently, the WHO was considering “something like a three-point scale in which different levels of severity can be conveyed,” according to Dr. Fukuda. Then, if a move to Phase 6 became necessary, the severity could at first be assessed as relatively low on the scale and moved up later.

Writing in the ‘Science Insider’ blog-site of the journal Science, Jon Cohen says the three-point scale of severity could be implemented in a country-specific manner. So, one country could be at Phase 6, Level 3 while others are at Phase 6, Level 1.

“Adding that requirement of severity may sound like common sense. But it is not, because the severity of a pandemic is unpredictable,” wrote Declan Butler in a news report published by Nature recently. “The flu might fizzle out; or it could go away for months only to come back with a vengeance, creating as much devastation as the 1918 flu outbreak.”

Moreover, “assessment of the severity of a pandemic is complex,” as the WHO itself observed in a recent issue of the Weekly Epidemiological Record. “Experience has shown that past influenza pandemics have varied in terms of severity, and that the associated health impacts may vary significantly based on a variety of factors.” It noted that severity could vary from country to country and even among populations or regions within a country.

The health impacts of a pandemic were determined by the characteristics of the virus, including the sort of disease it produced, the vulnerability of the population and the capacity of the population to respond, the WHO said.

Consequently, it asserted at the time that “a single assessment of severity at the global level may not be relevant or helpful to countries,” a point that Dr. Fukuda too made during earlier press briefings. In the same issue of the Weekly Epidemiological Record, the WHO suggested that “within each phase, countries may find it useful to assess the specific severity parameters of a pandemic at the national or regional level.”

However, now under pressure from its member-countries, the WHO is itself to provide such assessments of severity.

So far, the new flu virus appears to have produced relatively mild forms of the disease. In another issue of the Weekly Epidemiological Record, the WHO noted that only about 2 to 5 per cent of confirmed cases of infection were admitted to hospital in the U.S. and Canada while the proportion was 6 per cent in Mexico.

Almost half the patients hospitalised in the U.S. and about 46 per cent of the fatal cases in Mexico had underlying conditions such as pregnancy, asthma and other lung diseases, auto-immune disorders and associated treatments that would have led to the suppression of the immune system, neurological disorders and cardiovascular disease.

The seasonal flu that people catch can typically be life-threatening in the very young and the old. One of the characteristics of a pandemic flu virus is supposed to be a change in this pattern and a tendency for healthy young adults to show marked vulnerability.

The majority of those infected by the virus are under 60, Dr. Fukuda said at his recent press conference. Moreover, those who developed severe pneumonia or died from the infection tended to be in the age group of 20-40 years.

Dr. Fukuda preferred to characterise the current level of illness as “moderate” rather than “mild.” Neither the number of people with serious illness nor the number of those displaying symptoms across the entire spectrum of the disease was accurately known, he said. Besides, the infection could be fatal not only in those with underlying medical conditions but also in those who were healthy. “So we do have some hesitation in calling such an infection mild.”

One reason why older people are less vulnerable to infection and serious illness could be that they are more likely to harbour protective antibodies. Research by scientists of the U.S. Centres for Disease Control and Prevention published recently showed that about a third of Americans over 60 had antibodies that could latch on to the new virus strain. Although younger people had been vaccinated against seasonal H1N1 flu strains, few of them had protective antibodies against the new virus.

Those over 60 probably acquired the antibodies through infection with an H1N1 strain that the immune system found to be similar to the new virus, commented virologist Vincent Racaniello in his virology-related blog. “Whether such antibodies would confer protection against infection [by the virus] is unknown, but they could reduce the severity of disease symptoms.”

“For the first time in history, we are watching the conditions conducive for the start of a pandemic unfold before our eyes,” said Margaret Chan, Director-General of the WHO, in her closing speech to the World Health Assembly. “Scientists, clinicians and epidemiologists are capturing abundant signals. But we do not have the scientific knowledge to interpret these signals with certainty. We have clues, many clues, but very few firm conclusions.”