Abstract
The Lancet Conference on Influenza in the Asia–Pacific was held back-to-back with the International Scientific Symposium on Influenza A (H1N1) Pandemic Response and Preparedness organized by the Ministry of Health, People’s Republic of China, with support from the WHO. The conference has attracted scientists and clinicians from different parts of the world to share the most updated information on the current influenza pandemic, as well as key issues on seasonal influenza that are relevant to pandemic response. Several highlights are described here.
Virology of the pandemic H1N1 virus
The combination of gene segments of A(H1N1) pandemic (PDM) virus has not been reported previously. Reassortment had occurred between the North American triple reassortant and the European lineage of swine viruses. Those genetic markers for severe diseases observed in H1N1 Spanish flu or H5N1 highly pathogenic avian influenza virus were not found in the current PDM H1N1 virus. The PDM H1N1 viruses circulating worldwide are genetically and antigenically homogeneous, suggesting a single and recent introduction into humans. Thus far, no reassortment with the neuraminidase gene of seasonal H1N1 has occurred. Approximately 40% of the elderly over 65 years of age possessed serum antibody cross-reactive with A(H1N1) PDM virus, while the majority of children and adults younger than 65 years of age did not have such antibody. Vaccination with seasonal vaccines did neither induce nor boost immune response in any age groups. Data from animal models suggest that the virulence of A(H1N1) PDM is potentially higher than seasonal influenza viruses. So far, there is no significant difference in genetic and phenotype characteristics between viruses isolated from severe/fatal and mild cases.
Updated situation for the Western Pacific region
A total of 18 out of the 21 countries/areas in the Pacific region have reported cases of pandemic influenza. At the time of presentation, 136 deaths have been recorded in the Western Pacific region. Of those with clinical details, 75% had underlying medical conditions. Three deaths occurred in pregnant women who were previously healthy. Most places in this region have shifted or are shifting from ‘containment’ to ‘mitigation’. In conclusion, the virus has not undergone any significant mutations and the majority of cases have been mild. However, severe cases and death have been reported from countries with sustained community transmission. Intervention differs by different epidemiological stage. Therefore, it is important to shift accordingly at the right time. The Western Pacific Regional Office and the South East Asia Regional Office of the WHO have developed a framework for action to assist preparation in order to minimize preventable deaths.
Updates from China
In China, a national surveillance system was set up since the identification of the first clusters in North America. All suspected cases were admitted to designated hospitals for respiratory isolation, with the diagnosis confirmed by PCR. Close contacts were identified and quarantined at home or at designated hotels, and monitored daily for fever and respiratory symptoms for 7 days. At the time of presentation, there were 2741 confirmed cases in China. The median age was 20 years and ranged from 4 months to 75 years of age; 45% were under 18 years of age and only 0.4% were over 65 years of age. The confirmed cases included seven healthcare workers who had no personal protective equipments or only wore surgical masks while in contact with confirmed cases. Five teachers in two summer camps where an outbreak had occurred were also infected. Two flight crews who had contact with confirmed cases on board were also infected. More than 29 million individuals were scanned at boarder entries, which picked up 698 confirmed cases. Among the 20,329 close contacts under medical monitoring, 797 (3.9%) were confirmed to have acquired the infection. In summary, the novel H1N1 cases identified in mainland China predominately reflected importation from other countries during the early stage. The age profile of cases reflects the younger ages of travelers. Sustained community level transmission may have occurred in some areas with domestically acquired cases and local outbreaks.
Vaccine development & recommendations
Since May 2009, 13 candidate vaccine viruses have been developed and distributed in more than 400 shipments to manufacturers, regulatory authorities and research institutes. The output was expected to be reduced due to the lower yield compared with seasonal flu inactivated vaccines. The first vaccine available for use was targeted in September/October 2009. The pandemic baseline capacity was estimated at 94.5 million doses per week. The WHO is playing a coordination role in promoting access to available vaccines in low-income countries. As of 31 July 2009, a donation of 150 million doses has been committed by major manufacturers. The WHO recommends all countries to immunize healthcare workers as a first priority. A stepwise approach may be considered to vaccinate particular groups. Countries need to determine their order of priority based on country-specific conditions. Vaccination target groups include pregnant women (2% of the world population), those aged over 6 months with chronic medical conditions, healthy children, healthy young adults of 15–49 years of age, healthy adults of 49–65 years of age, and healthy adults over 65 years of age.
Vaccine production from China
China received the seed virus on 3 June 2009. The China CDC coordinated ten manufactures to recruit more than 13,000 subjects for clinical trials on the new pandemic vaccine. At the time of presentation, the results showed that the vaccines, both the 15 and 30 µg without adjuvant, were highly immunogenic with seroconversion rates over 85%. The safety profile was similar to seasonal vaccines. It was concluded that a single dose of 15 µg nonadjuvanted split vaccine could produce the required protective effect.
Antiviral resistance
Pandemic H1N1 is resistant to adamantanes, but susceptible to neuraminidase inhibitors oseltamivir and zanamivir. Sporadic isolates resistant to oseltamivir (H275Y) have been reported. At the time of presentation, oseltamivir-resistant viruses were isolated from 13 patients. The majority (eight) were on prophylaxis (75 mg daily). One case was on treatment (75 mg twice daily). Three cases were associated with prolonged therapy in immunocompromised patients. One case had a mixture of resistant and wild-type viruses detected from a respiratory sample, but only the resistant virus was isolated from cell culture. This case did not receive any antiviral treatment. The predominant pandemic virus remains resistant to both neuraminidase inhibitors oseltamivir and zanamivir.
Other key issues
The other key issues covered in the conference included the impact on vulnerable populations as learnt from Spanish flu experience, how modeling can guide the use of vaccine in an influenza pandemic, experience sharing from different countries on managing the initial phase of a pandemic, and how the control on seasonal influenza is related to pandemic preparedness.
The conference ended with recaps and conclusions from Lance Jennings (University of Otago, New Zealand). It was commented that this timely conference was an extremely successful one.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.