Jpn. J. Infect. Dis., 53, 2000

Laboratory and Epidemiology Commumications●SeroepidemiologlCal Survey of Influenza C Virus in
Hilroshima Prefecture, Japan
Shinichi Takao*, Akie Toyotal, Yhkie Shimazu, Shinji Fukuda, Masahiro Noda
and Shizuyo Tbkumoto

Division ofMicrobiology II and JDivision of Physics and Chemistyy,
Hiroshima Prefectural Institute ofHealth and EnviylOnment,
Minami‑machi 1‑6129, Minami‑ku, Hiroshima 734‑0007
Communicated by Hiroo lnouye(Accepted January 29, 2001)

Influenza C virus, which was first isolated from a patientage‑related distribution of HI antibody and the positive ratewith a mild innuenza‑like illness in 1947 (1), has beenin age groups against influenza C, A, and B viruses are shownconsidered an etiological agent for resplratOry infections inin Figures 1 and 2. Signi丘cant levels ofHI antibody‑positive

human beings (2). However,血e epidemiological infbmation

rate (134/186: 73･6%) against influen戸a C virus were foundregarding this virus, such as the mechanisms or its transmis‑in the sera tested, with the titers ranglng from 1:10 to I:80.

sionand maintenanceinnature, have been limited, as comparedwith those of influenza A and B viruses. We investigated theThe pattem of the HI antibody‑positive rate in age groups
agalnSt influenza C virus was markedly different from thoseantibody prevalence of this virus in the residents of Hiroshima
Prefecttwe to elucidatethe extent of influenza C viruSinfection,and inthis paper we reportthe results of the age distribution ofpositive rate (more than 50%) was shown only in the ageof influenza A and B viruses; a high percentage ofantibody‑antibody against influenza C virus in comparison with thosegroups of0‑ 14 years against A/Sydney/5/97(H3N2), Or in thatof 5‑24 and 30‑39 years against B/Harbin/7/94, while theagalnSt inmlenZa A and B vimses.

positive rate against A侶eijing/262/95(H IN 1 ) was generally

A total of 186 sera, which were collected from residents
living in Hiroshima Prefecture in the age range of 0‑84 years
in 1997, were measured for hemagglutinin‑inhibition (HI)antibody titer against influenza A, B, and C viruses. The

low ln all age groups. In contrast, the antibody‑positive rate
against C什Iiroshima/290/99 was high in all age groups except

for that of 0‑4 years. Similar antibody‑prevalence pattems inage groups agalnSt influenza C virus have also been reported

仰Ⅷ 帥 ㈹ 側 2tFJaS^P!OdLpoqt[VJOa3q JaLa)PLpoqpt 8tH

4020051015202530

3540

45505560

65707580(Ago)Fig. 1. Age‑related distribution of antibody andantibody‑positive rate in age groups against innuen2a CviruS. Hemagglutination‑inhibition (HI) titers of 1 86 sera collected from residents of Hiroshima Prefecture in 1997 were determir.63d using themicroplate technique described by Homma (3). Theantigen for HI test was the isolate of innuenza C virus (C/Hiroshima/290/99) (5). HI liters were expressed as the reciprocal of highest serum dilutionthat inhibited hemagglutination, and wereplotted against age. The pcrcentages of antibody‑positive sera (HI titer of 1 : 1 0 or more) were determined every 5 years ofage, and are shownas bars onthe graph.

*Corresponding author: Fax: +8 1 ‑82‑25218642, E‑mail: takao@
urban.neJp246

Jpn. J. hfect. Dis., 53, 2000

been declining markedly in the era ofHJWT, which includes
the use of two nucleoside reverse‑transcriptase inhibitors

Lipodystrophy syndrome can cause cardiovascular complica‑
tions (5). Therefore, older patients should likely begiven PI‑PRTIs)andanHIV‑speci丘c protease inhibitor (PI) ･ However･

spanng reglmenS tO avoid complications. Our obseⅣations

adherence to these reglmenS IS Often difrlCult because of theappear to suggest that the nTyelotoxicity of ZDV can belarge number of pills, side effects, and drug‑drug interactions
related to PIs. Furthermore, reports of unexpected serious side

exacerbated by NVP. It maytherefore be important to be awareof this potential side effect, especially during the first 5 weeks

effects in patients exposed to PIs over a long period areof ther叩y ln elderly patients.

increaslng ln number. In particular, metabolic disturbancessuch as increased levels of cholesterol or triglycerides andThis study was supported by grants from the Ministry of

insulin‑resistant diabetes in association with abnormal fat

Health and Welfare of Japan, and the Organization for
Pharmaceutical Safetyand Research (OPSR) of Japan.

redistribution, which is referred to as lipodystrophy syndrome( 1 ), have been observed. Non‑nucleoside reverse‑transCriptase
inhibitors (NNRTIs) are advantageousdue tothe lower burden

REFERENCES

ofpills and fewer drug‑drug Interactions compared with PI.
Therefわre, HAART consistlng Of 2 NRTIs and 1 NNRTI isI. Carr, A., Samaras, K., Burton, S., Law, M., Freund, J.,

being prescribed as initial therapy ln treatment‑naive patients,Chisholm, D. ∫. and Cooper, D. A. (1998): A syn血omeand ̀switch ther叩y'with NVP in place of PIs is beingof peripheral lipodystrophy, hyperlipidemia and insulinprescribed for patients with long‑term sustained viral suppres‑resistance in patients recelVlng HIV protease inhibitors.

a洗er its approval (3). However, there has been little infoma‑

AIDS, 12, F51‑58.
2. Barreiro, P., Soriano, V., Blanco, F., Casimiro, C., de lasion (2).Leukocytopenia caused by ZDV was reported soontion regarding myelotoxicitycaused by antiretroviral regimens

Cruz, ∫. ∫. and Gonzalez‑Lahoz, ∫. (2000): Risks andcontalnlng NVP in adults. At our hospital, 44 patients havebeen treated with NVP‑containlng reglmenS Since 1997.

benefits of replaclng PrOteaSe inhibitors by neviraplne

in HIV‑infected subjectsunder long‑termsuccessful triple
combination therapy. AIDS, 14, 807‑8 12.

Seventeen underwent reglmenS COntainlng NVP and ZDV.

Asdescribed above, 3 out of 17 patients (17.6%) developed
leukocytopenia 315 Weeks after the commencement of

3. Richman, D. D., Fischl, M. A., Grieco, M. H., Gottleb,M. S., Volberding, P. A., Laskin, 0. L., Leedom, J. M.,

antiretroviral therapy. In cases 1 and 2, regimens including

Groopman, ∫. E., Mildvan, D., Hirsch, M. S., Jackson,

ZDV and NVP were introduced as the first antiretroviraltherapy, resulting in leukocytopenia. In case 1, ZDV wasreplaced by d4T, while 3TC and NVP were not changed in

G. G., Durack, D. T., Nusinoff‑Lehrman, S. and AZTCollaborative Working Group (1987): The t?xicity ofthe second reglmen, this patient had no further episodes ofADSand AIDS‑related complex. A double‑blind, placebo‑
controlled trial. N. Engl. J. Med., 317, 192‑197.

azidothymidine (AZT) in the treatment of patlentS With

leukocytopenia. Although case 3 had been treated with ZDV/
ddt since I 996, he had never developed leukocytopeniauntil
dual‑PIs were changed to NVP. These observations appear to4. D'Aquila, R. T., Hughes, M. D., Jolmson, V A., Fischl,M･ A., Sommadossi, J. P., Liou, S. H., Timpone, J., Myers,

indicate that luekocytopenia by ZDV might be intensified byM., Basgoz, N., Niu, M. and Hirsch, M. S. (1996):

NVP.

Neviraplne, Zidovudine, and didanosine compared with

Toxic hepatitis and Stevens‑Jolmson 's syndrome have been

zidovudine and didanosine in patients withHIV‑ 1 infec‑tion. Ann. Intem Med., 124, 1019‑1030.

reported as serious adverse events associated with NVP.
However, in previous studies of NVP in combination with
ZDV, serious leukocytopenia has not been reported among

5. Henry, K., Melroe, H., Huebsch, ∫., Hemundson, ∫.,the more than 400 participants studied (4). In our cases, thepremature coronary artery disease with protease inhibi‑

patients were relatively older. If advanced age is a predispos‑
ing factor for leukocytopenia, this will have clinical relevance.

tors. Lancet, 51, 1328.

Levine, C., Swensen, L and Daley, ∫. (1998): Severe245