Division of International Health (Public Health)

Influenza virus

  インフルエンザはオルソミキソウイルスに属するマイナス一本鎖のRNAウイルスで、急性呼吸器感染を引き起こします。インフルエンザウイルスは核蛋白の血清型からA,B,C型に分けられます。A型インフルエンザは、表面抗原のヘマグルチニン(HA)とノイラミニダーゼ(NA)蛋白の種類により、さらに亜型に分けられています。インフルエンザは人獣共通感染症ですが、通常人間に感染するのはA/H1N1, A/H3N2とB型です。A型インフルエンザは周期的にパンデミック(世界大流行)を起こすことが知られており、2009年には北米の豚に由来するA/H1N1インフルエンザがパンデミックを起こしたことは記憶に新しいと思います。



 近年、インフルエンザ感染症に対して抗ウイルス薬で治療が可能となりました。日本で保険適応されているのはM2阻害剤のアマンタジンと、ノイラミニダーゼ阻害剤のオセルタミビル、ザナミビル、ペラミビル、ラニナミビルです。M2阻害剤はA型インフルエンザにのみ有効ですが、ノイラミニダーゼ阻害剤はA型、B型インフルエンザ双方に有効です。症状がでてから48時間以内に治療を開始すれば、有熱期間が1-2日短縮されます。抗インフルエンザ剤は治療後に耐性が出現することが知られています。M2阻害剤では治療後の約1/3に、ノイラミニダーゼ阻害剤のオセルタミビルではA/H1N1の約1割に耐性が出現します。一般的に耐性株は伝播力が弱いとされており、これまで耐性株が流行することはないと考えられてきました。しかし、2005年にアジアを中心にアマンタジン耐性A型が大流行し、2007年にはヨーロッパに端を発したオセルタミビル耐性A/H1N1株が世界中で流行しました。幸い、インフルエンザA/H1N1 2009(新型インフルエンザ)に耐性株の流行はまだありません。

 当教室では、インフルエンザの分子疫学と薬剤耐性に焦点をあてて研究を行っています。これまで日本のみならずミャンマー、ベトナム、レバノン、極東ロシアなどでインフルエンザの調査を行ってきました。ミャンマーでは世界的に珍しいザナミビルとアマンタジンの二重耐性A/H3N2を検出し英文誌に報告しました。(Dapat et al., EID 2010)

Influenza is negative sense RNA virus belongs to Orthomixoviridae, and causes acute respiratory infections to humans. Influenza virus is classified into type A, B and C by nucleoprotein. Influenza A is further classified into subtype by combination of various type of two surface proteins, hemagglutinin and neuraminidase. Influenza causes infections to various animals, and normally influenza subtypes A/H1N1 and A/H3N2 and type B infect humans. Influenza A is known to cause pandemic periodically, and in 2009 influenza A/H1N1 (A/H1N1 pdm) originated from swine in North America caused pandemic. Since then, A/H1N1pdm replaced seasonal A/H1N1, and circulates with influenza A/H3N2 and B.

Influenza causes epidemic during winter time in temperate countries, but limited information is available on circulation of influenza in tropical areas. Previous studies show in tropics influenza is detected throughout year, but outbreaks are likely to occur during rainy season. We have clarified seasonality of influenza in North Vietnam and Myanmar where information was limied.

Another question remains with influenza is where new strains of influenza occur in the world. Most recently, a source-sink model of influenza virus evolution has been proposed, whereby new virus variants preferentially emerge out of the tropics, in particular from East-SouthEast Asia, and seed epidemics in temperate areas. One of our purposes is to

Other focus is antiviral resistance of influenza. Currently, two types of anti-influenza drug are in clinical use in Japan, M2 inhibitors (amantadine) and neuraminidase inhibitors (oseltamivir, zanamivir, peramivir, laninamivir). M2 inhibitors are effective for influenza A, but neuraminidase inhibitors are effective for both influenza A and B. Both drugs can reduce illness days by 1- 2 days when they are administered within 48 hours of symptom onset. It is reported that one third of influenza patients can develop resistance after treatment by M2 inhibitors and 10% by one of neuraminidase inhibitors, oseltamivir. Viral resistance is derived from point mutation at functional protein (M2 protein or neuraminidase), and in general, fitness at the time of human to human transmission is reduced with resistant strains compared to wild strains. Thus it was believed resistant strains do not increase in the community. However, in 2005 amantadine resistant influenza A showed a dramatic rise in community circulating strains without pressure of the M2 inhibitors and then in 2007, oseltamivir resistant influenza A/H1N1 (seasonal) caused epidemic firstly in Europe and spread to the rest of the world. Thus, picture for drug resistant influenza strains are changing in recent years. So far, there is no increase of oseltamivir resistant strains in A/H1N1 pdm in the community.

Niigata University is one of National Universities in Japan located North West of Japan main island, and working on influenza viral surveillance. We are focusing on molecular epidemiology and anti-viral resistance of influenza. In the past, we investigated influenza not only in Japan but various countries such as Myanmar, Vietnam, Lebanon and Far East Russia, which is regarded as hot spot in influenza dynamics. We found rare double resistant strains for zanamivir and amantadine in influenza A/H3N2 in 2007 and 2008 in Myanmar and reported to international English journal (Dapat et al., EID 2010).

Niigata University is not only working on analyses of influenza, but has ability to upgrade influenza laboratory for molecular diagnostics. We worked with national laboratories in Vietnam and Myanmar, and the two laboratories were designated as National Influenza Center in WHO Global Influenza Surveillance Network.