All four dengue virus serotypes have occurred in French Polynesia. The first epidemic of dengue on Tahiti island of known serotype (dengue 1) occurred in 1944 as part of the Pacific-wide spread of the disease during World War II. The next outbreak of dengue took place in 1964 and was the result of the introduction of dengue 3 virus. With the increase in air travel by humans, dengue has occurred as successive epidemics, especially between 1969 and 1979 with each epidemic involving a different serotype. Each time, the epidemic serotype replaced the unique endemic serotype that had been transmitted during the preceeding interepidemic period: dengue type 3 in 1969, dengue 2 in 1971, dengue 1 in 1975-1976 and dengue 4 in 1979. With the exception of the dengue 2 epidemic, during which severe haemorrhagic cases and several deaths were observed on Tahiti on 1971, cases of dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) were not common. Following a long inter-epidemic period involving a low transmission of dengue 4, two back-to-back epidemics of dengue 1 and dengue 3 took place during 1988-1989. Of great interest was the occurrence of DHF/DSS in the latter epidemic (11 fatalities) while mildness characterized the former. Surveillance of both epidemics involved clinically and laboratory-based systems. Public health control measures were instituted. These viruses were throughoutly spread in the Pacific region with varying degrees of disease severity. Molecular epidemiology studies provided new information on geographic distribution, origin, evolution and strain variation among dengue viruses

Chungue Eliane

Glaziou Philippe

Laudon Francois

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Trop･ Med･, 35 (4), 209-215, December, 1993 209Dengue and Dengue Haemorrhagic Feverin French Polynesia-Current SituationEliane CHUNGUE1, Francois LAUDON2 & Philippe GLAZIOU1Unit of Virology, Institut Terri･tonal de Recherches Medicates Louis Malarde,P. O. Box 30, Papeete, Tahiti, French Polynesia & 2Epidemiology-Statistics Section,Direction de la Sante Publique, P. 0･ Box 611, Papeete, Tahiti, French PolynesiaAbstract : All four dengue virus serotypes have occurred in French Polynesia. The firstepidemic of dengue on Tahiti island of known serotype (dengue 1) occurred in 1944 as part ofthe Pacific-wide spread of the disease during World War II. The next outbreak of denguetook place in 1964 and was the result of the introduction of dengue 3 virus. With the increasein air travel by humans, dengue has occurred as successive epidemics, especially between 1969and 1979 with each epidemic involving a different serotype. Each time, the epidemic serotypereplaced the unique endemic serotype that had been transmitted during the preceeding inter-epidemic period: dengue type 3 in 1969, dengue 2 in 1971, dengue 1 in 1975-1976 and dengue4 in 1979. With the exception of the dengue 2 epidemic, during which severe haemorrhagiccases and several deaths were observed on Tahiti on 1971, cases of dengue haemorrhagicfever/dengue shock syndrome (DHF/DSS) were not common. Following a long inter-epi-demic period involving a low transmission of dengue 4, two back-to-back epidemics ofdengue 1 and dengue 3 took place during 1988-1989. Of great interest was the occurrence ofDHF/DSS in the latter epidemic (11 fatalities) while mildness characterized the former.Surveillance of both epidemics involved clinically and laboratory-based systems. Publichealth control measures were instituted. These viruses were throughoutly spread in thePacific region with varying degrees of disease severity. Molecular epidemiology studiesprovided new information on geographic distribution, origin, evolution and strain variationamongdengue viruses.Key words : Dengue, epidemiology, surveillance, current situation, French PolynesiaHISTORICAL BACKGROUNDDengue viruses are the only mosquito-bone flaviviruses involved in FrenchPolynesia･ All four dengue virus serotype have occurred in epidemic form during the last50 years･ The first epidemic with known serotype was due to dengue 1 in 1944 as part ofthe Pacific-wide pandemic (Rosen, 1958)･ The reappearance of the disease paralleled withthe advent of jet air travel and the increased urbanization of French Polynesia in the 1960's･210Thus, a succession of epidemics occurred at short intervals : dengue 3 in 1964-1965 and1969, dengue 1 in 1971, dengue 1 in 1975-1976, dengue 4 in 1979 (Laigret et al., 1967;Saugrain et al., 1970 ; Moreau et al, 1973; Kaueffer et al., 1976; Pare et at., 1981a and1981b). From 1980 to 1988, transmission of dengue continued at a very low level (Chungueet al, 1989).THE RECENT EpIDEMICSTwo successive epidemics took place recently : dengue 1 in late December 1988 anddengue 3 in August 1989･ The trend and the surveillance of these epidemics have beendescribed in details elsewhere (Chungue et at., 1992 ; Chungue et al., 1990). Briefly,surveillance of both epidemics was followed by ( i ) weekly reporting of the number ofpatients diagnosed by sentinel physicians (a case of dengue was defined as a patient whopresented with a sudden onset of febrile illness with any of 2 of the following symptoms :headache, myalgia, arthralgia, rash or haemorrhagic manifestations), (ii) the weeklynumber of requests for laboratory confirmation, (iii) the number of virologically and/orserologically confirmed cases (virus isolation on C6/36 cell cultures and detection of denguespecific lgM by MAC-ELISA)･ Epidemic control involved adulticidal measures and lar-vicidal source reduction for both epidemics. Information messages were delivered onvector control, on minimizing risk of infection, and on the procedure to be adopted in theevent of illness･Dengue 1 epidemic : December 1988-June 1989 : In December 1988, dengue 1 viruswas isolated from a 15 years old child who presented with a dengue-like illness. Thepatient lived in a suburb of Papeete. Subsequent survey showed that 2 family contactsharboured lgM anti dengue antibodies二　Epidemic transmission was recognized in lateDecember･ Although control efforts were initiated few days after, the epidemic developedexplosively and reached its peak in Tahiti island in February (Fig･ 1). The serologicalattack rate was about 44%, 4 months after the onset of the epidemic. Among 6,034 casesreported by sentinel physicians, 60.3% were<20 years old･ The illness was classicaldengue. No fatality or case of dengue haemorrhagic/dengue shock syndrome (DHF/DSS)was reported. Of 1,752 documented cases, 701 (40%) were confirmed in laboratory･ TLefrequency of the various clinical symptoms among these confirmed cases are shown inTable l･ Overall, laboratory diagnosis of 4,836 patients resulted in 41% of confirmed cases(Table 2)･ Primary infection was predominant. Virus isolation from mosquitoes pro二vided evidence that dengue 1 was transmitted by Aedes aegypti.Dengue 3 epidemic : August 1989-May 1989 : While the dengue 1 epidemic wasdeclining, dengue 3 was detected for the first time since 1969, in Bora Bora island, in midApril. Overall 3 strains were identified between April and May･ One or them wasisolated in the neighbouring island of Raiatea･ A few cases were detected between June211and July in Tahiti. Although French Polynesia was at high risk of epidemic dengue 3,transmission was rather low until September (Fig･ 1)･ The peak was reached in October-November･ The epidemic stretched out on several months, and epidemic transmissionlasted about 8 months･ As of March 1990, 6,330 cases were reported by sentinel physicians･Of ll fatal cases, 10 occurred in children under 15 years old･ Of 838 documented casesrecorded between August to February among ambulatory patients, 266 (31･7%) werelaboratory confirmed. The frequency of clinical symptoms was shown in Table 1. Themajor features of dengue 3 epidemic were its high frequency of cases with minor haemorr-rM650600ササ5004507Ja　400(すォ　350二･■サ!ra子=250星　200150IBM500｢]∩!l言JrlDengue 1- Reported cases□ Suspected cases■Co血med casesDengue 3III!IIIIII!IIII･IIIIIIIII卜l二1子tー1l二I1二Tm51 1 3　5　7　9 111315171921232527293133353739414345474951 1 3　5　7　9 1113151719211 988　　　　　　　　　　　　　　　　　　　　　1989Calendar weekFig･ 1･ Dengue 1 epidemic (Dec･ 1988二June 1989) and Dengue 3 epidemic (Aug. 1989-May1990) : Weekly distribution of dengue cases･Table l･ Frequency of clinical symptoms observed in laboratoryconfirmed dengue patientsClinical symptomsFrequency (%) amonglaboratory confirmed patientsDengue 1 Dengue 3n-701　　　　　n=266Fever/ H eadache/Myalgi aAdenopathiesMacular rashDigestive signs (vomiting, nausea, diarrhoea)Taste alterationsPrurit/ParesthesiaHeamorrhagic signs (epistaxis, petechia, purpura)Hepatalgia/HepatomegalyPapular rash5.3　　　　　　　･722･　　　　　　15.420.9　　　　　　15･719･　　　　　　34.616.1　　　　　19.99.9　　　　　　13･95.1　　　　　14.35.04･7　　　　　　　9･7212Table 2. Virological and serological results from suspected cases submitted tolaboratory confirmation of dengue diagnosisEpidemicNo･ of No･ of positive Totalsusp∝ted cases Virus isolation Mac-ELISA PositivesDengue 1(Dec. 88-Jun.Dengue 3(Aug. 89-May 90)4,836　　1,198 (24.7%)　778 (16･0%)　1,976 (40.8%)5,583　　　589 (10.5%)　768 (13･7%)　1,357 (24･3%)hagic signs (14･3%) and the occurrence of cases severe enough to require hospitahzation･Furthermore, cases with thrombocytopenia were high (26･3%)･ Among 232 laboratoryconfirmed children hospitalized in the public civilian hospital of Papeete, 55･6% presentedwith hemorrhage, 30･1% with DSS, 63% with thrombocytopenia, 46% with SCOT > 99 IU,55% with hepatomegaly, 40 % with a neurologic disorder (Glaziou et al., 1992). Among178 individuals for whom the type of HI antibody response was determined, 39% had aprimary infection. DSS was observed in both primary and secondary infection (41% vs30%)･ Of 5,583 patients subjected to laboratory confirmation, 24% were confirmed (Table2)･ This confirmation rate was low compared to that observed during dengue 1 epidemic(41%)･ Whether this lower rate was due to clinical overdiagnosis in a context of moresevere manifestations related to dengue 3 or to the lower frequency of virus isolation sincemost of cases are secondary infections, is difficult to assess･ Fur仙ermore, serologicaldiagnosis was mostly performed on single serum specimen and level of lgM is known to belower in secondary infections･ However, the serological attack rate was estimated atabout 49% in December 1989 (Chungue et al., 1992).The study of these epidemics emphasize the need of both clinically and laboratory-based system for an adequate surveillance of epidemic, and for early warning system･CuRRENT SITUATIONRecent advances in dengue diagnosis : Urgent diagnosis by RT-PCR in case ofsuspicion of DHF/DSS was made available since we described a rapid, simple and efficientsingle-tube procedure for dengue viral RNA extraction from small amount of serum (10//1).Recovery of RNA is based on the lysing and nuclease-inactivating properties ofguanidinium thiocyanate in the presence of silica. The RT/PCR can be completed within5 hours starting from the RNA extraction to agarose gel electrophoresis. (Chungue et al,1993)･surveillance : Since 1988, the surveillance of dengue fever is based on the monitor-ing of reported cases by physicians, of suspected cases (cases in whom a laboratoryconfirmation of the diagnosis is seeked) and of confirmed cases (virologically and/or213serologically positive)･ Moreover, because of its immediate availability, the weekly inci-dence of suspected cases has been shown to be a valuable indicator of dengue activitytogether with the confirmation rate (Chan et al., 1977 ; Chungue et al., 1991). A suddenrise in laboratory requests urged to a号urvey among sentinel physicians.The nature of the virus serotpype is continuously monitored･ In order to tracemovement of dengue viruses over time and geography, molecular techniques were used inrecent studies (Deubel et al., 1992). Evidence that the recent epidemics were due to theintroduction of a new variant rather than the re-emergence of early viruses through silenttransmission was shown (Chungue et al., in press). For instance, the recent Polynesianepidemic dengue 3 virus strain clustered in a genotypic group that comprised recent strainsfrom Indonesia and New Caledonia･ Analysis of dengue 1 strains showed relatednessbetween recent Polynesia Strain (1988) and isolate from a Caribbean strain (unpublisheddata). Identification of virus strain regarding their genotypic grouping might of interestfor a better understanding of the epidemiology of dengue viruses, and for vaccine develop･ment.In view of continued entomological survey and vector control our effort are concen二trated to the international airport area during interepidemic period while a community-based vector control is promoted by the public health service, especially in Tahiti.Situation in 1993 : Table 3 summarizes the yearly distribution of dengue cases from1988 to 1993･ Since its introduction dengue 3 is continuously transmitted (Fig･ 2) withsporadic severe cases (2 fatalities in 1992)･ In view of risk of epidemic dengue, whenconsidering the distance from the more recent known serotypes epidemics and the subse-quent sizeable population born after them, French Polynesia is at high risk for dengue 2epidemic, and at a lesser extent, for dengue 4 epidemic･Table 3･ Yearly distribution of dengue cases in French Polynesia, 1988-1993YearNumber of casesReported Suspected Confirmed H ospitali zed *1988　　　262 (197)a　　　512 (111)1　　　78 (44)'1989　　12,3971990　　　3,6051991　　　　5781992　　　　　6091993　　　　248b7,976　　　　　　2,13,0501,1981,451504b61815924887b1972044574Total 17,699　　　　14,691　　　　4,073　　　　　　521a : numberreported on weeks 51 and 52 of 1988; : up to June 1993-- : not available* : from public civilian hospital214160014001200[り｢q.)詔　1000oで　800q)J⊃良　6004002000�"Reported cases□ Suspected casesI Confirmed cases三三三∠LiLliTva ~　二一二_-_二�".�"/E--_�"A O D F AJA O D F AJA O D F AJA O D F AJA1989 I　1990　　　　1991　　　　1992　　　　1993Fig. 2. Current situation : Monthly distribution of dengue 3 cases, 1989-1993･In conclusion, improved laboratory-based surveillance, genetic investigation ofcirculating viruses, disease surveillance, health education programme, vector controlprogramme are adopted for an efficient surveillance system.AcKNOWLEDGMENTSThis work was supported by the Government of French Polynesia and the Mmisterede la Recherche et de l'Enseignement Superieur (decision 87-L-0557), France. We thankM･ Lefevre, C, Roche, 0. Cassar, M･ Gay and the clinical laboratory, N･ Maruhi, D. Ch6ouand all the sentinel physicians and the hospital physicians for their assistance･REFERENCES1) Chan, K. L., Ng, S. K･ & Chew, L. M･ (1977), The 1973 dengue haemorrhagic fever outbreak insingapore and its control. Sing･ Med･ J. 18, 81-93.2 ) Chungue, E･, Marchfi, G., Plichart, R., Boutin, J-P. & Roux, J (1989) : Comparison of immunoglobulinG enzyme-linked immunosorbent assay (IgG-ELISA) and haemagglutination inhibition (HI) test forthe detection of dengue antibodies･ Prevalence of dengue lgG-ELISA antibodies in Tahiti. Trans. Roy.soc. Trop. Med･ & Hyg., 83, 708-711･3 ) Chungue, E., Spiegel, A., Roux, J., Laudon, F. & Cardines, R. (1990) : Dengue 3 in French Polynesia :preliminary data. J. Med. Aust･, 152, 557-558.4 ) Chungue, E･, Boutin, J-P. & Roux, J･ (1991) : Dengue surveillance in French Polynesia : an attempt to215use the excess number of laboratory requests for confirmation of dengue diagnosis as an indicator ofdengue activity･ Eur･ J･ Epidemiolリ7, 616-620.5 ) Chungue, E., Burucoa, C., Boutin, J-R, Philippon, G., Laudon, F., Plichart, R., Barbazan, P., Cardines,R･ & Roux, J. (1992)二Dengue 1 epidemic in French Polynesia, 1988-1989 : surveillance and clinical,epidemiological, virological and serological findings in 1752 documented clinical cases. Trans. Roy.Soc･ Top･ Med･ Hyg･ 5, 193-197･6) Chungue, E･, Glaziou, P., Spiegel, A･, Martin, P･ M. V. & Roux, J･ (1992): Estimation of dengueinfection attack rate in a cohort of children during a dengue 3 outbreak in Tahiti. Southeast AsianJ･ Trop. Med. Public Health., 23, 157二158.7) Chungue, E･, Roche, C., Lefevre, M-F･, Barbazan, P. & Chanteau, S. (1993): Ultrarapid, simple,sensitive, and economical silica method for extraction of dengue viral RNA from clinical specimensand mosquitoes by reverse transcriptase-polymerase chain reaction. J. Med･ Virol, 40, 142-145.8 ) Chungue, E., Deubel, V., Cassar, 0., Laille, M. & Martin, P. M. V. (1993) : Molecular epidemiology ofdengue-3 viruses and genetic relatedness among dengue-3 strains isolated from patients with mild orsevere form of dengue in French Polynesia. J. Gen. Virol･ in press.9 ) Deubel, V･, Nogueira, R二, Drouet, M. T., Zeller, H･, Reynes, J･ P. &Ha, D. Q･ (1993) : Direct sequencingof genomic CDNA fragments amplified by the polymerase chain reaction for molecular epidemiologyof dengue -2 viruses. Arch. Virol., 129, 197-210.10) Glaziou, P., Chungue, E., Gestas, P･, Soulignac, 0., Couter, J-P･, Plichart, RリRoux, J. & Poll, L. (1992) :Dengue fever and dengue shock syndrome in French Polynesia. Southeast Asian J･ Trop. Med. PublicHealth., 23, 531-532･ll) Kaueffer, H., Pichon, G., Merlin, M., Carme, B., Riviere, F., Rosen, L. & Laigret, J. (1976) : A proposd'une 6pid6mie contrSlee de dengue en Polynesie Frangaise. Med. Trop., 36, 455-459･12) Laigret, J., Rosen, L. & Scholammer, G. (1967) ‥ Sur une epidemic de dengue survenueえTahiti en 1964･Relations avec les "Fievres Hgmorragiques" du Sud-Est Asiatique. Bull. Soc° Path. Exot･, 60 (4), 339-353･13) Moreau, J-P., Rosen, L･, Saugrain, J. & Lagraulet, J. (1973): An epidemic of dengue on Tahitiassociated with hemorrhagic manifestations･ Am. J. Trop- Med. Hyg., 22, 237-241･14) Pare, F･, Tetaria, CリPichon, G･, Louis, F. & Laigret, J･ (1981a) ‥ La dengue due au virus de type 4 enPolyngsie Fran∈aise･ I. Epidemiologie generate. Aspects cliniques particuiers. Med. Trop., 41, 97- 102.15) Pare, F･, Tetaria, C･ & Pichon, G･ (1981b) : La dengue due au virus de type 4 en Polynesie Frangaise.II. -Observations biologiques liminaires sur quelques points precis d'epidemiologie et de physiopath-ologie. Med･ Trop., 41, 97-102･16) Rosen, L･ (1958) : Dengue antibodies in residents of the Society Islands, French Oceania. Am･ J. Trop.Med･ Hyg., 7, 403-405･17) Saugrain, J., Rosen, L., Outin-Fabre, D･ & Moreau, J-P･ (1970) : Une rgcente gpid&mie d'arbovirose dutype dengue畠Tahiti. Comparaison avec I'6pid6mie de 1964. Bull. Soc･ Path. Exot, 63 (6), 631･641･

Dengue and Dengue Haemorrhagic Fever in French Polynesia-Current Situation

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Dengue and Dengue Haemorrhagic Fever in French Polynesia-Current Situation

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