The Topic of This Month Vol. 30, No. 10 (No. 356)
The virus has had different names since its discovery, but now the WHO's official name is influenza A (H1N1)pdm (abbreviated as AH1pdm below), and the disease caused by it is called pandemic (H1N1) 2009.
Start of the epidemic in Japan: On April 28, in response to elevation of the WHO pandemic alert level to phase 4, the pandemic (H1N1) 2009 was classed as "pandemic influenza and relevant infections" under the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections (Infectious Diseases Control Law), and quarantine measures were enforced immediately. On May 9, three passengers including high school students coming back from Canada via USA were found infected with AH1pdm (see p. 257-258 of this issue). On May 16, the first domestic infection was found in Kobe City and Osaka Prefecture, which were probably epidemiologically unrelated. Further investigation revealed outbreaks in Osaka and Hyogo Prefectures mostly among high school students (see p. 266 of this issue). The immediate measures taken were to ask feverish patients to consult "fever consultation centers" first and then under the centers' guidance to visit "fever clinics", to isolate all the laboratory-confirmed cases in the designated hospitals, to close schools in the affected area temporarily, and to request close contacts to remain at home. Such measures were effective in preventing further local spread of the infection (see p. 259 of this issue). From mid June on, however, the pandemic influenza spread Japan wide (Fig. 1), and by July 16 no prefecture was left unaffected (see p. 260-265 of this issue).
Surveillance in Japan: In early phase of the epidemic, in compliance with the Infectious Diseases Control Law, laboratory diagnosis of all the suspected cases and notification of all the diagnosed influenza patients were norms. On July 24, however, after reporting of 5,038 confirmed cases, the norm was replaced by cluster surveillance (reports of outbreaks in various settings) and hospital admission surveillance for severe cases, in addition to routine sentinel surveillance, pathogen surveillance, school absentee surveillance (reports of school outbreak of ILI). At the same time, the law-based isolation of the patients in hospitals was discontinued.
Influenza sentinel surveillance in Japan that started in 1987 is based on weekly report of ILI from sentinel points (currently approximately 5,000 sentinels including 2,000 clinics of internal medicine and 3,000 clinics of pediatrics). About 10% of them are pathogen sentinels too. Specimens obtained in the pathogen sentinels and those obtained from outbreaks and serious cases were sent to the prefectural and municipal public health institutes (PHI) for virus isolation and identification. The isolates were then sent to National Institute of Infectious Diseases (NIID) and analyzed for antigenicity, genetic characterization, and drug susceptibility.
As all the feverish patients had to go to "fever clinics" initially, the number of influenza cases reported from influenza sentinels remained at a low level. But it started to increase from week 28 (July 6-12) when the "fever clinics" were discontinued and consultation of feverish patients was allowed in general clinics including sentinel clinics. The number of cases per sentinel reached 1.69 on week 33, far exceeding 1.00, an indicator of the start of an influenza epidemic. On week 38 (September 14-20), it reached 4.95 (Fig. 2) and the total number of the influenza patients who visited the medical facilities in this country in the week was estimated to be 270,000. In Okinawa Prefecture, the influenza patients increased sharply towards the end of July and attained 46.31 cases per sentinel at its peak in week 34 (see p. 264 of this issue).
In May when the AH1pdm virus was first isolated in Japan, subtype AH3 was dominant, but from week 24 (June 8-14) on, AH1pdm started to dominate, and, since July, almost all the influenza patients were infected by AH1pdm (Fig 2 & Fig 3 and http://idsc.nih.go.jp/iasr/influ-e.html).
Reports from school absentee surveillance and cluster surveillance indicated that temporary closures owing to the influenza outbreak were increasing among schools and other places in September after summer vacation.
Symptoms and prognosis: The symptoms of pandemic (H1N1) 2009 are pharyngitis, sudden onset of high fever, cough, running nose and general fatigue, almost indistinguishable from those of the seasonal influenza (see p. 266 of this issue). The case-fatality rate calculated by using the Mexico outbreak data was 0.4-0.5%, which was equivalent to that of Asian flu and higher than that of the seasonal influenza 0.05%. People with ailments like asthma, diabetes, heart diseases, and decreased immunity occupied half of the fatal cases. Highly obese people and pregnant women in the third trimester are considered at high risk.
Though the fatal case has been small in number in Japan yet, severe cases have increased with the increase of the patients; 54 patients needing artificial respirators (see p. 267 of this issue), 34 patients of acute encephalopathy (see p. 268 of this issue), and 17 fatalities among 1,323 hospitalized patients have been reported to the Ministry of Health Labour and Welfare (MHLW) as of September 29. While most fatal cases were adults, the majority of hospitalized patients were children. About 40% of the hospitalized patients had background ailments (http://www.mhlw.go.jp/bunya/kenkou/kekkaku-kansenshou04/index.html).
Laboratory diagnosis: As early as May 1st, PHIs and major quarantine stations were ready to conduct PCR diagnosis of AH1pdm using primers and positive controls provided by NIID (the primers were designed by NIID using the data published by Center for Disease Control and Prevention, USA). It is important to note that the rapid diagnosis kit for antigen detection that is widely used in clinics in Japan cannot detect the antigen, including that of AH1pdm, during the onset of fever, but, on one day later, it detects the antigen-positives more efficiently.
Treatment: In Japan, antiviral drugs have been used for treatment of the influenza patients and they should not be used for prophylaxis in principle. Antiviral drug therapy can be started without the laboratory data. The viruses with H275Y mutation associated with oseltamivir resistance have been isolated in Denmark, Japan (see p. 270 of this issue), Hong Kong, USA, Mexico and other countries, but they have not posed clinical problems yet.
Vaccines: The influenza vaccines licensed in Japan are adjuvant-free, embryonated chicken egg-derived ones. After having produced 80% of the amount of the seasonal influenza virus vaccine prearranged for the 2009/10 influenza season, production was switched to pandemic influenza AH1pdm vaccine. The vaccine strain chosen was A/California/7/2009(H1N1)pdm-like recommended by WHO, and the production method was the same as that used for the seasonal influenza virus. The projected production scale is equivalent to 54,000,000 doses (or for 27,000,000 persons if each person receives two doses). The proposed vaccination targets are, in the order of priority, medical staff, pregnant women, persons with ailments, children from 1 year old to the 3rd grade of the primary school, and parents of 0-year-old children. If the vaccination targets are extended to all students at primary, secondary and high schools and to elderly, however, the domestic production may not be able to cope with the amount required. Adjuvant-combined vaccines and vaccines derived from tissue culture cell grown virus are produced in abroad.
Conclusion: As preparedness for the expansion of the epidemic, enforcement of surveillance, consolidation of the medical services, procurement of sufficient amount of therapeutics and vaccines are in immediate need. For assisting treatment of serious cases, the past experience with the influenza encephalopathy and experience of the respiratory control are placed on the MHLW website, http://www.mhlw.go.jp/kinkyu/kenkou/influenza/hourei.html.
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