ON June 11, the World Health Organisation (WHO) raised the current worldwide epidemic of the new influenza virus A(H1N1), commonly called swine flu, to the status of a pandemic, the highest level of global alert. This is the first flu pandemic in 41 years. The last one was the 1968 Hong Kong flu.
The world is now at the start of the 2009 influenza pandemic, announced Margaret Chan, the WHO Director-General, at a press briefing. On the basis of available evidence and expert assessments of the evidence, the scientific criteria of an influenza pandemic have been met.
As of June 12, this hitherto unknown form of A(H1N1)-type flu virus, which was first seen in Mexico in April now identified as reassortment of human influenza A(H1N1) and North American and Eurasian swine influenza viruses (Frontline, June 5, 2009) had spread to 74 countries, with a total of 29,669 laboratory-confirmed swine flu cases including 145 deaths (see map). In India, of the 237 persons tested, 16 tested positive for this new virus: Hyderabad eight, Coimbatore two, Delhi five and Goa one. Of these, two are indigenous, who caught the infection from relatives who had returned with infection from abroad. Interestingly, 155 of these were self-reported and the rest identified through screening at airports.
On a six-point WHO alert classification (Frontline, June 5), Phase 6 is characterised by community-level outbreaks in at least one other country in a different WHO region in addition to the criteria for Phase 5. The latter is when human-to-human transmission of the virus spreads to at least two countries in one WHO region from where it is exported as isolated cases to other regions. It is strongly indicative of an imminent pandemic and is a call to finalise national-level organisation, communication and implementation of mitigation measures. On April 29, the WHO raised the alert status to Phase 5 following the finding of sustained human-to-human transmission and of spreading within communities in Mexico and the United States.
It must be emphasised here that the alert status only refers to the extent of the geographical spread and the efficiency of transmission, and not to the severity of the disease. Going from Phase 5 to 6 only means that the spread of the virus has continued and the activity has become established in at least two regions of the world. It does not mean that the severity of infection has changed.
Globally, Margaret Chan said, we have good reason to believe that this pandemic, at least in its early days, will be of moderate severity. As we know from experience severity can vary, depending on many factors, from one country to another. The severity is assessed on the basis of scientific evidence available to the WHO as well as inputs from its member-states on the diseases impact on health systems, society and the economy.
The virus has been found to preferentially infect people under the age of 25. While the disease appears to be largely self-limiting, there have been a number of serious cases. In some of the countries with large and sustained outbreaks, 2 per cent of the cases developed severe illness typically pneumonia or respiratory failure requiring ventilators, sometimes ending fatally and most cases of severe and fatal infections have been in adults between the ages 30 and 50, according to Margaret Chan. This pattern is significantly different from that seen in seasonal influenza, when most deaths occur in frail elderly people.
On present evidence, she added, the overwhelming majority of patients experience mild symptoms and make a rapid and full recovery, often in the absence of any form of medical treatment. Worldwide, the number of deaths is small. However, we do not expect to see a sudden and dramatic jump in the number of severe or fatal infection. We know, too, that this early, patchy picture can change very quickly.
The virus writes the rules and this one, like all influenza viruses, can change the rules, without rhyme or reason, at any time. Perhaps of greatest concern [is that] we do not know how this virus will behave under conditions typically found in the developing world. Although the pandemic appears to have moderate severity in comparatively well-off countries, it is prudent to anticipate a bleaker picture as the virus spreads to areas with limited resources, poor health care and a high prevalence of underlying medical problems.
But there have been criticisms from some health experts that the WHO had delayed the declaration of a pandemic, the criteria for which had been met weeks ago. Keiji Fukuda, the Assistant Director-General, had responded to this criticism in a press briefing on June 9 saying that the WHO had been working extremely hard in terms of preparing countries for what a potential move to Phase 6 would entail, and to avoid panic and misunderstanding that might lead to actions that in the end would cause more anxiety among the people. It was important for the WHO to also explain the level of severity of the current situation with any announcement about a pandemic, he had said.
In his briefing, Fukuda pointed out that approximately half the people who died had been previously healthy people. This is one of the observations that has given us the most concern, he said. Apparently, there had been a lot of push by different groups to say that the pandemic was mild.
From the outset, Fukuda said, we knew a number of deaths that had taken place among younger people who were previously healthy. This is a pattern that we have seen with the H5N1 virus [avian flu], this is a pattern and a consequence that we have seen in earlier pandemics and it continues to give us a great deal of concern.
In effect, therefore, the announcement on raising the epidemics status from Phase 5 to 6 does not warrant any drastic steps by countries, different from what they had been doing earlier. It sends out an important message to countries that irrespective of what state the epidemic is in their country, they must maintain continuous vigilance they must be on the watchout for the arrival of the infection and start to prepare their people and health systems to deal with the arrival of the new disease, Margaret Chan said.
She, however, struck a note of optimism by saying, We are in the earliest days of the pandemic. The virus is spreading under a close and careful watch. No previous pandemic has been detected so early or watched so closely, in real time, right at the very beginning. The world can now reap the benefits of investments [for avian flu] over the past five years in pandemic preparedness. We have a head start, she said.
India had been following a phase-wise approach advocated by the WHO for averting an avian flu epidemic and for the containment of a novel virus. In the present case, given the widespread transmission that is already evident in many countries, the WHO does not advocate a containment strategy in general. India has, however, been following a containment strategy until now. You can only do containment for some weeks and if you are seeing continuing spread of infection in the community, it is important they move to mitigation measures, Margaret Chan pointed out.
According to Vineet Chowdhury, Joint Secretary, Ministry of Health and Family Welfare (MoHFW), since the disease has not spread in India and there are no clusters [more than five transmissions from a single case], the containment strategy will be continued. According to the MoHFWs document Pandemic Preparedness and Response for Managing Novel Influenza A(H1N1) (or that arising from any other novel strain of Influenza), an action plan intended to be used in Phase 5 and 6, when India gets affected with a small cluster and transmission is not efficient, cluster containment strategy could be enforced provided it is supported by the requisite legal, administrative, technical and resource support. The defined population in a geographic area would be subjected to active house to house surveillance, contact tracing and chemoprophylaxis by giving oseltamivir [Tamiflu] to every individual in a prescribed geographic limit of 5 km from the epicentre (village/city where the cluster is reported). [I]f one person infects two persons in 3 days (15 cases in 10 days), containment may be difficult but yet possible. If the spread is more than this, containment is less likely. Widely dispersed multiple clusters would indicate that the clusters cannot be contained through the geographic approach.
India has currently a stock of 10 million doses of oseltamivir for chemoprophylaxis, according to the MoHFW document. This stock is enough for 714,000 people. Some stocks are also committed by pharmaceutical companies for exclusive use by the government. This drug is available only through the public health care system. If there is widespread infection, MoHFW would review this decision. For worst case scenario, the stockpile held by WHO would also be tapped, says the document.
As regards worldwide availability of a vaccine, Margaret Chan said, At least there is equity now. No country has pandemic vaccine for the next few months because normally it takes about four to six months to make a vaccine. For the next three months or so, no country would have vaccine. Even when we get into September and beyond, there will be limited supply, and the challenge for the world is to look at who should get the vaccine and within a country which groups get the vaccine.
According to the WHO vaccine expert Marie-Paule Kieny, vaccine manufacturers have been standing ready to start production for quite a number of weeks now. All of them have received the vaccine virus, which allows them to go into large-scale preparation, she said. According to her, a very small number has already been able to start and the other ones will start next week or the week after that.
When enough evidence is available in the coming weeks we will make policy recommendations on which population should be prioritised for the use of the first doses of the vaccine, she said.
In an MoHFW press briefing on June 12, Chowdhury said that the National Institute of Virology (NIV), Pune, had isolated the virus from Indian cases, which would be used to develop an indigenous vaccine. He added that the Indian government had also asked the WHO for the seed virus.
The WHO agreed to give it to India with the condition that if India succeeded in developing the vaccine the produce should be available for global use. Both the Indian isolate and the WHO isolate will be used for producing the vaccine by three manufacturers: Panacea Biotec, New Delhi; Bharat Biotech, Hyderabad; and Serum Institute of India Ltd. (SIIL), Pune. The first two will make cell-based vaccine and the SILL will grow the virus in eggs. If the development is successful, production should take six months to a year at least.
From a genetic perspective, the virus, as we see today, is relatively the same as the virus that was first seen in April, according to the WHO. In a recent paper in the advance online version of the journal Science, Rebecca J. Garten from the WHO Collaborating Centre for Influenza at the Centres for Disease Control and Prevention (CDC), United States, and others have pointed out that the antigenic variation among the 2009 A(H1N1) viruses circulating in humans is currently less than that seen during a typical influenza season. Analysing 76 isolates from Mexico and 12 U.S. States, they have found the identity to be 99.9 per cent.
The authors point out that molecular markers predictive of adaptation to humans, seen in the 1918 H1N1 strain that killed 40 million-100 million people worldwide, are not currently present in this new virus, suggesting that previously unrecognised molecular determinants could be responsible for the transmission among humans.
Interestingly, however, the new 2009 Influenza virus A(H1N1) of swine origin seems to have filled in the off-season period of conventional seasonal flu (see graph) outbreaks. So how the virus will evolve, if it is still circulating when the seasonal flu virus is widespread during the winter months, remains a medically interesting question.