Dengue in : Major Features, Surveillance, Molecular Epidemiology and Current Situation∗

By Eliane Chungue, Xavier Deparis & Bernadette Murgue Institut Territorial de Recherches Médicales Louis Malardé P.O. Box 30, Papeete, , French Polynesia, Fax : 689-43 15 90, e-mail: [email protected]

Abstract

The emergence of dengue epidemics worldwide has paralleled the expansion of the vector aegypti, along with jet air travel and increased urbanization. All the four serotypes (DEN-1, 2, 3 and 4) have occurred in epidemic form during the past 50 years in French Polynesia. The first epidemic with a known serotype was due to DEN-1 which occurred in 1944 during World War II. The disease disappeared from the Eastern Pacific after a Pacific-wide pandemic, but a series of epidemics occurred at short intervals during two decades: DEN-3 in 1964-1965, DEN-2 in 1971, DEN-1 in 1975-1976, and DEN-4 in 1979. From 1980 to 1988, the transmission of DEN-4 continued at a very low level until the resurgence of DEN-1 and DEN-3 in back-to-back epidemics in 1989. In 1996, DEN-2 reappeared in Tahiti and spread further into , the , Tonga, and .

As in most Pacific countries, epidemics with only one serotype have occurred in French Polynesia. Each time, the genetic analysis of the causative viruses showed that the current epidemic ______

∗ Reproduced from Pacific Health Dialogue 1998, 5(1):154-162 with the permission of the Editor

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was due to the introduction of a genotype which was different from the viruses recovered from the past epidemics. These observations emphasize the need for an active system of clinical and virological surveillance for the prevention and control of epidemics, together with molecular characterization of the viruses as part of the investigation of a dengue epidemic. As of now, a new genotype of DEN-2, different from the one involved in the 1970s, is disseminating throughout the Pacific region.

Keywords: DF/DHF, DEN-1,2,3,4, epidemic, molecular epidemiology, French Polynesia.

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Introduction

French Polynesia, situated in the South Pacific Ocean, consists of five Epidemiological features archipelagos (Society, Tuamotu, Gambier, Austral and ) comprising 120 islands, of Epidemic pattern which only 66 are inhabited. Most of has been known the population is concentrated in the clinically in French Polynesia since the Society archipelago which nineteenth century, with documented encompasses the Windward and the epidemics in 1852, 1870, 1885 and Leeward islands. Tahiti, the largest 1902(1,2,3). The first outbreak of island of French Polynesia in the dengue in Tahiti of a known serotype Windward group, contains the Capital, occurred in 1944 as part of the Papeete. During the past 40 years the Pacific-wide spread of the disease population of French Polynesia has caused by DEN-1 during World War undergone a dramatic increase. Since II(4). The disease disappeared from the 1946, it has trebled in 30 years, and it Eastern Pacific after the pandemic and, has doubled between 1966 and 1988. as far as is known, did not reappear The last census (1996) recorded a until 1964 and 1969, when DEN-3 population total of 219 521 which is was involved(5,6). From that time on, unequally distributed: 74% of it is epidemics have occurred at shorter concentrated in the Windward Islands, intervals: DEN-2 in 1971, DEN-1 in especially on Tahiti, of which 77% live 1975 and DEN-4 in 1979 were in the urbanized Papeete. In all areas successively epidemic(7,8,9). With the the climate is hot and tropical. A hot exception of the DEN-2 outbreak, rainy season from November to April during which severe haemorrhagic alternates with a cooler, drier season cases and three deaths were observed from May to October. The annual on Tahiti in 1971, mildness of the average temperature and rainfall in disease characterized these past Tahiti is 25.7°C and 2 m, respectively. epidemics. A recent succession of These climatic conditions are epidemics took place after nine years consistent with the year-round of continued transmission of DEN-4. mosquito breeding. Back-to-back epidemics involving

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DEN-1 and DEN-3 occurred in 1988- 1989. It is noteworthy that dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) occurred in the latter epidemic (11 fatalities) while mildness characterized the former. These viruses were spread throughout the Pacific region with varying degrees of disease severity(10).

Epidemics with only one serotype have occurred. Each epidemic serotype replaced the previous serotype that had been transmitted during the inter-epidemic period. Simultaneous transmission of both serotypes was only observed for a short period of time (2-4 months) when the epidemic serotype was taking place. During these periods, co-circulations were demonstrated for DEN-2/DEN-1 in 1975, DEN-1/DEN-4 in 1979, DEN-1/DEN-3 in 1989, and DEN-3/DEN-2 in 1996. The endemic virus was generally swept out 7 weeks to 4 months after the recognition of the new epidemic. This is illustrated by Fig.1a and Fig.1b.

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Figure 1a. DEN-1 and DEN-3 epidemics (1988-1990): Monthly distribution of dengue virus serotypes

350 Dengue 1 300 Dengue 3

s 250

200

15 0 Number of isolate 10 0

50

0 DJFMAMJJASONDJFMAMJJA

1988II 1989 1990

Figure 1b. DEN-2 epidemic (1996-1997): Monthly distribution of dengue virus serotypes

350

300 Dengue 3 Dengue 2 250

200

Number of isolate 15 0

10 0

50

0 JFMAMJJASONDJFMAMJJASO

1996 I 1997

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Morbidity and mortality serological surveys, the proportion of asymptomatic infections was Although accurate data regarding estimated to be 30%(8,11,12). During an morbidity are not available, a review outbreak the mortality rate is usually of published and unpublished low (see Table 1). The morbidity trend literature allowed us to obtain of the epidemics is also illustrated by estimates of dengue infection in the the number of (i) clinical cases Windward Islands during the major reported by physicians (reported epidemics which occurred between cases), (ii) cases for which a request 1944 and 1997 (Table 1). Estimated for laboratory confirmation is made morbidity rates were calculated by (suspected cases), and (iii) virologically using the data obtained by serological and/or serologically confirmed cases and/or epidemiological surveys. The (Table 2). The annual incidence rate estimation of the attack rates involved during the inter-epidemic periods antibody prevalence in cohorts of (endemic transmission) is unknown. susceptible populations and One study that concerned the long measurements of absenteeism in inter-epidemic period between 1980 schools and government and business and 1987 showed an acquisition rate offices. The serological attack rate was of dengue antibodies of 3% per year in generally around 50% as determined a cohort of susceptible children(13). immediately after the epidemic transmission. According to clinical and

Table 1. Morbidity and mortality of dengue during major epidemics between 1944 and 1997 in the Windward Islands (French Polynesia)

No.of Population Estimated Year of No. of fatal infected Serotype Windward Is. morbidity epidemic cases persons (1000’s) rate(%) (1000’s)

1944 DEN-1 29.8 62 - 26

1964-65 DEN-3 55.2 20 - ND*

1969 DEN-3 79.1 ND* - ND*

Dengue Bulletin – Vol 22, 1998 79 Dengue in French Polynesia: Major Features, Surveillance, Molecular Epidemiology and Current Situation

1971 DEN-2 84.5 50 3 42.2

1975-76 DEN-1 94.6 25 - 34.1

1979 DEN-4 104.2 25 - 37.5

1988-89 DEN-1 140.3 17 - 35.1

1989-90 DEN-3 143.9 25 11 49.5

1996-97 DEN-2 162.6 19 1 43.5

*ND: not determined.

Table 2. Dengue cases reported during the epidemics in French Polynesia, 1964-1997

Number of Year of epidemic Serotype Reported cases* Suspected cases Confirmed cases

1964-65 DEN-3 1358 – –

1969 DEN-3 72 – –

1971 DEN-2 12943 – –

1975-76 DEN-1 2032 2018 694

1979 DEN-4 7489 1783 630

1988-89 DEN-1 6034 4836 1976

1989-90 DEN-3 6330 5583 1357

1996-97 DEN-2 7230 4424 2027

– data not available; *Institut Malarde & Direction de la Sante

Transportation and spread intensive movements of human populations among and into areas that of virus were permissive to dengue In addition to the lack of effective transmission during World War II. mosquito control, the origin of the Hence, in 1944, an extensive epidemic Pacific-wide pandemic of DEN-1 of dengue occurred in the Society (1941-1945) was very likely related to archipelago, French Polynesia.

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Together with entomological surveys increased seaport activity. In the in other Pacific islands(14,15,16), the 1960s, important changes in the evidence of experimental transmission ecology of dengue in French Polynesia of dengue virus between monkeys occurred after the construction of the suggested that Aedes polynesiensis international airport in 1960-1961. served as a natural vector in the past This event suddenly brought French epidemics in French Polynesia(14). Polynesia into the modern era, with Conversely, the geographical accelerated urbanization that distribution of the disease and the paralleled an increasing number of entomological surveys carried out dengue outbreaks. The increase of during the post-war epidemics (1964- population in Papeete and its 1996) were more consistent with the surrounding localities comprised of role of Ae. aegypti as a vector. For workers recruited from the rural part instance, while Ae. aegypti was of Tahiti and from neighbouring reported in 1953 in Tahiti, its islands. Between 1956 and 1988 the presence had expanded progressively population of Tahiti rose from 50% to throughout French Polynesia, which 76% of the total population of French was coincidental with the advent of Polynesia; of these, 79% resided in inter-island air connections: in the urban areas. The expansion of Papeete 1970s in the Tuamotu, in 1982-1986 led to the growth of adjacent suburbs. in the Marquesas Islands, and in At this time, the metropolitan Papeete 1979-1986 in the (17). lied along a 40 km coastal border only a half kilometre wide. The size and frequency of dengue epidemics are related directly to social The first re-introduction of and economic development, especially dengue viruses was related to multiple urbanization(18,19). For instance, the factors: increased jet air travel, high first urbanized locale, Papeete, density of susceptible population in became so in 1850 during the urban areas, and lack of mosquito European colonization. Coincidentally, control. Papeete was hit by a DEN-3 the first occurrence of dengue on epidemic in 1964, as was Makatea Tahiti was reported in 1852. The island, a nearby island of the Tuamotu disease was limited to Papeete which archipelago whose urban areas were had been recently urbanized with an subjected to exploitation of

Dengue Bulletin – Vol 22, 1998 81 Dengue in French Polynesia: Major Features, Surveillance, Molecular Epidemiology and Current Situation phosphates. Regular exchanges of the epidemics may be seen in the existed between these two sites, in dynamics of the recent epidemics. Fig. both of which Ae. aegypti were 2 shows clearly that the DEN-1 abundant. The limited transmission epidemic in 1988-1989 moved from within these areas was apparently the Windward Islands to the Leeward related to the sparse distribution of Islands and on to the Marquesas and Ae. aegypti in most islands of French Austral Islands(21). Furthermore, DEN- Polynesia(5). A flare-up of DEN-3 was 3 was first detected in the tourist reported in 1969 in Papeete(6). island of in the Leeward Islands, and spread subsequently to The speed and frequency of Tahiti, then to the remote human exchanges by jet air travel archipelagoes(21). These situations make possible the introduction of were consistent with the fact that dengue viruses by a dengue-infected inter-island air travel was more traveller from hyperendemic areas. A intense between Tahiti and the parallel has been observed between Leeward Islands than with the the spread of dengue viruses and the Marquesas and Austral Islands. route and frequency of air travel between the infected and the permissive areas within the Pacific Clinical features (20) region . This was exemplified by the The disease has been generally mild. epidemics which occurred in the However, dengue illness caused by all Pacific islands in the 1970s, which four serotypes is naturally always emerged from countries/areas accompanied by haemorrhagic which had intensive international manifestations(22). In most epidemics, traffic. The disease has spread a proportion of cases presented with secondarily from these points to minor haemorrhagic signs:15% in neighbouring island countries. For 1964 (DEN-3), 4% in 1969 (DEN-3), 3% instance, in 1979 the first occurrence in 1971 (DEN-2), 15% in 1975-1976 of DEN-4 outside Asia was observed (DEN-1), 5% in 1989 for epidemic on Tahiti. Three years later, DEN-4 DEN-1, 14% for epidemic DEN-3, and had spread to many islands of the 18% in 1996-1997 for DEN-2. The Pacific. At the country level, in French two occurrences of severe Polynesia, the geographical diffusion

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Figure 2. DEN-1 epidemic (1988-1989): Geographical distribution of reported cases, by week

500 Windward Is. e Leeward Is. 400 M ar q u esas an d Au st r al I s.

300

200 Number of reported cas Number 100

0 51 52 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Calendar week 1988-1989

manifestations requiring hospitalization were in 1971 (33 Socioeconomic impacts cases, 3 fatalities) and 1989-1990 (401 cases, 11 fatalities). The 1971 In islands with limited populations, epidemic involved mostly adults (63%) dengue fever is generally an epidemic while children represented 69% of the disease. In Asia, where the occurrence cases in 1989-1990, an outbreak in of DHF/DSS is frequent, the social and which haemorrhagic manifestations economic cost is high (US $31.48 (24) were observed among 59% of the million per year in Thailand ). hospitalized children. In 1996, among However, epidemics of the classical the 232 hospitalized children, the disease are not to be overlooked. For number of severe forms was low (19 instance, during the last epidemic of cases), and the proportion of children DEN-1 in French Polynesia, of the 161 presenting with haemorrhagic subjects from whom a reply to the manifestations was 36%. Only one question about the number of days death (adult) was reported(5,6,7,8,10,23). absented from work was obtained, 125 indicated a 3-5 days of absence.

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Moreover, in the 1996-97 DEN-2 Commission) and local authorities, a epidemic, the direct costs were network of dengue control and estimated to be US $2.5 million, surveillance was set up. Subsequent including laboratory costs, funding supported the development of hospitalization, and medical care. The a community-based vector control indirect costs, including morbidity- programme. Despite the implementa- related absenteeism from work, the tion of preventive measures, an cost of lost production and prevention epidemic occurred a short time later. and control activities was around US Epidemic control involved adulticiding $1.98 million. The estimated total cost of mosquitoes using ultra low volume worked around US $4.48 million (i.e. (ULV) spraying of insecticides. US $20 per inhabitant). From this Larvicidal source reduction measures study, it was evident that the involved the destruction or treatment estimated total cost of the 1989-90 by insecticides of breeding sites. DEN-3 epidemic, including the Educational programmes accompanied (8) DHF/DSS cases, was US $40 per these measures . During the 1979 DEN-4 epidemic, similar measures inhabitant, whereas the estimated cost were implemented. After these series of the 1988-89 DEN-1 epidemic was of epidemics, the control programme US $15 per inhabitant. Estimation of was maintained at a minimum level the costs for loss of tourism was not which comprised continued health made. education and limited entomological surveillance at the international airport Surveillance, prevention and at a few sentinel stations. and control Finally, the only constant and Before 1975, the DHF epidemics did immediately available surveillance not benefit from any special control system is the laboratory-based programme. They were generally system. Laboratory capabilities were explosive and ended after exhaustion reinforced, and modern and rapid viral of the susceptible population. In 1975, and serological analyses were made Tahiti was expected to have DEN-1 available. Urgent diagnosis of virus reintroduced from Fiji. With the suspected DHF/DSS was carried out by efforts of both regional (South Pacific reverse transcriptase polymerase

84 Dengue Bulletin – Vol 22, 1998 Dengue in French Polynesia: Major Features, Surveillance, Molecular Epidemiology and Current Situation chain reaction (RT-PCR), allowing a Caledonia(28). Subsequently, DEN-2 was result within as little as one day(25). detected instead. Since 1988, the surveillance of dengue The detection of a serotype fever has been based on the different from the one which is monitoring of (i) cases reported by endemically transmitted constitutes a physicians; (ii) suspected cases; and very important feature while (iii) confirmed cases. Trends of considering whether further epidemic dengue activity and the virus serotype transmission might occur. A are continuously monitored. retrospective analysis of the situation Actually, the weekly incidence of in French Polynesia in recent years suspected cases constitutes a valuable shows that a new epidemic followed indicator of dengue activity(26,27). Since each detection of a new serotype in a all the diagnoses are made only in our sizeable susceptible population in a laboratory, the data are immediately country where mosquitoes were always available. A sudden rise in laboratory present. In 1988, the first isolation of requests precipitates an immediate DEN-1 in Tahiti island intervened telephone survey among sentinel during a nine-year inter-epidemic physicians. In addition, through a small period of a low-level incidence of DEN- group of selected sentinel physicians, 4(11). The epidemic peaked a few weeks any increase in dengue-like illness is after, and the disease spread reported and investigated. Blood throughout most of the islands of specimens are obtained from French Polynesia. The first isolation of representative cases and processed to DEN-3 was observed in April 1989 in detect dengue infection by virus Bora-Bora island, then in June 1989 in isolation or RT-PCR and/or dengue IgM Tahiti island. The epidemic was antibody detection. In addition, recognized in August in Tahiti(21). information on dengue activity in the Furthermore, the recent DEN-2 Pacific region is taken into account in epidemic peaked in January 1997 after order to stimulate awareness in the the first case was detected by medical community or to set up timely laboratory survey in August 1996. sentinel surveillance, as happened in Thus, virological surveillance is of 1996 when DEN-4 was detected in New importance for an early warning surveillance system.

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Molecular epidemiology epidemiology of DEN-2 viruses is particularly worthy of emphasis. By using molecular techniques, the transmission pathways of the viruses Nucleotide sequencing of have been suggested and seem to different parts of the genome as short corroborate with the descriptive fragments or entire genes (prM, E or epidemiology. Analyse of genome NS3) allowed several authors to sequence relatedness demonstrated perform comparative analysis of a genotype groupings among all four large variety of dengue virus strains. DEN virus serotypes(29). Thus, one to Sequence data obtained recently in five genotypes were defined among our laboratory or those retrieved from virus strains isolated in different published databases were compared geographic areas and over periods within each serotype virus. Hence, ranging from 33 to 53 years. Each fragments of the E protein gene of (i) genotype seems to have a defined 180 nucleotides (nt 82 to 261) from focus of endemicity. However, certain DEN-1 and DEN-4 viruses, (ii) 198 genotypes appeared to have been nucleotides (nt 85 to 282) from DEN-2 transported to another part of the viruses, and (iii) 195 nucleotides (nt world where they became established. 73 to 267) from DEN-3 viruses were Different transmission pathways of compared(29). A divergence of 6% these viruses around the world are within the studied region was taken as pointed out, and co-circulation of two a cut-off point for virus groupings. or more genotypes in the same Three genotype groups were geographic region has been observed, defined for DEN-1 viruses, and especially for DEN-2 viruses. The first clustering of virus isolates for which genetic evidence of the existence of a linkages would be expected on sylvatic cycle of dengue virus, clearly epidemiological grounds was different from outbreak viruses, was observed(32). Genetic relationships demonstrated, and further confirmed were detectable over a 50-year span by molecular analysis(30,31). Owing to (, 1944, to the Indian Ocean, the current circulation of dengue 1993). For instance, earlier epidemic viruses in our region, the molecular strains from the Pacific (1974-1978)

86 Dengue Bulletin – Vol 22, 1998 Dengue in French Polynesia: Major Features, Surveillance, Molecular Epidemiology and Current Situation clustered in genotype 1 while recent strain derived from mutation through epidemics strains from French silent transmission. Furthermore, a Polynesia and New Caledonia (1988- high level of dissemination of DEN-1 1989) and the Comoro Islands genotype 2 during recent years, as (1993), as well as from French shown by the clustering of the viruses Guiana, Guadeloupe, Puerto Rico, recently isolated in countries that Brazil, Peru, Nicaragua and Cuba, fell have ties with French tropical in genotype 2 (as do the American countries (French Guiana, French strains). Therefore, it is likely that the Pacific territories, Comoro Islands) recent epidemics of DEN-1 in the was suggested, although the Pacific region are due to the direction of the spread was not introduction of a new variant of virus determined. rather than theFigure re-emergence 3. Molecular of epidemiology a of DEN-2 viruses

TORRES STRAIT 96 BURKINA FASO 83 SOMALIA 84 INDONESIA 76 1 SRI LANKA 85a SRI LANKA 85b SRI LANKA 90a SRI LANKA 89 SRI LANKA 90b Dengue 2 PHILIPPINES 83 TAIWAN 87 BURMA 76 THAILAND 64 NEW GUINEA 44 2 CUBA 81 THAILAND 80d JAMAICA 83 VIETNAM 87 VIETNAM 96 FRENCH GUIANA 90 TAHITI 96 COOK 97 3 NEW CALEDONIA96 QUEENSLAND 92 PUERTO RICO 69 TONGA 74 4 INDIA 57 TAHITI 75 TRINIDAD 57

SENEGAL 74 5 SENEGAL 81 BURKINA FASO 80

0 2 4 6 8 10 12 14 16 18 20 % Divergence

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The maximum divergence over Samoa isolates in the same genotype. the E protein gene fragment was This new genotype is significantly approximately 20% among DEN-2 distinct from the previous virus viruses. The dendrogram shown in groups (9% divergence with genotype Fig. 3 depicted five genotypic groups 4). The Tahiti 1996 strain presented a and agreed generally with previously 12.5% difference with the earlier (30,31,33) published phylogenetic trees . Tahitian virus (1975), and agreed with the evidence of a virus recently Two genotypes have been introduced rather than to the involved in the Caribbean. The hypothesis of a new variant derived Jamaican genotype (genotype 2) was from earlier virus. Its closer genotype confirmed as to be related to virus is genotype 1, in which isolates from strains from South-East Asia (97.5% Torres Strait (D. Phillipps, personal similarity with Vietnamese 1974 and communication), Burkina Faso or Sri 1996 strains). As mentioned by Lanka fell. Guzman et al.(33), the Cuban strain (1981) was closer (98% similarity) to Four genotypes were defined the old New Guinea C strain (1944) among 30 isolates of DEN-3 viruses and clustered in the same genotype 2. with the entire gene or restriction The Puerto Rican strain is shown to be analysis(34). The first group contained transmitted in the Caribbean, Central isolates from the South Pacific (1988 America, India, and the South Pacific to 1995), Singapore (1973) and (Tonga 1974, Tahiti 1975) within the Indonesia (1973 to 1991). The second genotype 4. Interestingly, the recent group comprised the viruses from virus isolated during the actual Asia (1956 to 1995) including the epidemic on Tahiti in 1996 falls into a reference strain H-87 and the new genotype (genotype 3) together Vietnamese strains (1974 and 1995). with recent isolates from New The third was composed of one isolate Caledonia. Data sequence from D. from Thailand (1971). The fourth Phillipps (personal communication) genotype included the early strains allowed also the classifycation of 1992 from French Polynesia (1964 to 1969) Queensland, 1997 Cook Islands and and from Puerto Rico (1963).

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Maximum divergence over the studied the three other serotypes since the region was approximately 12% and maximum divergence was 20% for corresponded to the distance between DEN-2 viruses, 12% for DEN-3 viruses, the early (1964 and 1969) and recent and 6.9% for DEN-1 viruses. However, (1989 to 1995) Polynesian/New microheterogeneity was observed Caledonian DEN-3 strains. Hence, it is within DEN-4 geographic strains that unlikely that the recent isolates result clustered in two subgroups. from a genetic mutation of the Interestingly, the recent isolate from remaining endemic virus, since no New Caledonia (1996) appears to be DEN-3 virus has been isolated within a more closely related to the viruses 20-year period. Therefore, as for from Indonesia. This variant was DEN-1, these data suggest that the present for only a few weeks in early recent epidemics in the Pacific are due 1996. Whether its failure to be to the introduction of a new variant transmitted intensively is related to a virus rather than the re-emergence of weak adaptation of the virus to its a strain derived from mutation vector and /or host or to unfavourable through silent transmission. Moreover, climatic conditions, combined with an there is a sequence similarity between active vector control programme, is a New Caledonian strain (1988) difficult to state (M. Laille, recovered four months before the unpublished data). Moreover, recognition of the epidemic. This transportation of virus from one favours the hypothesis of the continent to another is illustrated by emergence of DEN-3 epidemics in the the isolation of the Haiti 1981 strain in Pacific from Indonesia via New Senegal from a patient who had just Caledonia after several months of arrived from Haiti(31). latency. These studies demonstrated that

DEN-4 viruses seem to occur as a dengue viruses could be identified and classified in genotypic groups that single genotype around the world. The may circulate concurrently in the same sequence variation in the same region region. Moreover, in some instances, of the E protein gene among DEN-4 the origin of the newly introduced viruses was lower (4.9%) than among

Dengue Bulletin – Vol 22, 1998 89 Dengue in French Polynesia: Major Features, Surveillance, Molecular Epidemiology and Current Situation virus has been suggested. For change is involved in the instance, close relationships between pathogenicity of DHF/DSS. the Polynesian strains (1964 and 1969) and the Puerto Rican (1963) DEN-3 strain or between the Current situation Polynesian (1975) and Puerto Rican Fig. 4 illustrates the yearly distribution (1969) strains or Trinidad (1957) DEN- of the suspected and confirmed 2 strains, suggest possible virus dengue cases from 1988 to 1997. exchanges between the Caribbean and Since its recent introduction, DEN-2 the South Pacific owing to the frequent has been continuously transmitted. In trades from Europe via the Panama view of the risk of epidemic dengue, channel. The South Pacific-American when considering the time elapsed connection was also suggested by the since the last epidemic of a given close genetic relationships between serotype and the size of the DEN-4 viruses (99 to 100% homology). population born subsequently, French In more recent years, the introduction Polynesia is at high risk for the of a new virus in the South Pacific reintroduction of DEN-4, and to a seems to be more related to frequent lesser extent, of DEN-1. Retrospective air travel exchanges with Indonesia observations concerning the (DEN-3 in 1989, and DEN-4 in 1996). epidemiology and control of the Each time, a new epidemic was due to recent epidemics showed that the introduction of a new genotype. emergency adulticiding and larvicidal The current DEN-2 virus spreading control have to be applied from Tahiti to New Caledonia and the immediately after the detection of the Cook Islands belongs to the same first emergence of either virus. genotype. This emphasizes the Advantage may be taken of the usual efficient dissemination of viruses one-to- several months of the time among these island countries through lag before the recognition of an intra-regional travel. Furthermore, epidemic. certain genotypes of the viruses have In conclusion, improved been associated with severe disease laboratory-based surveillance, genetic potential. However, it is still unclear investigation of circulating viruses, whether any particular molecular disease surveillance (specific and

90 Dengue Bulletin – Vol 22, 1998 Dengue in French Polynesia: Major Features, Surveillance, Molecular Epidemiology and Current Situation febrile diseases), health education D. Pons for their secretarial programmes, and vector control assistance. programmes must be promoted for the better prevention and control of References

Figure 4. Yearly distribution of dengue in French Polynesia, 1989-1997

9000 60%

8000 Su sp e c t e d c ase s Confi rmed cases 50%

s 7000 % confirmed cases

6000 40%

5000 30%

Number of case 4000

3000 20%

2000 10 % 10 0 0

0 0% 19 8 8 19 8 9 19 9 0 19 9 1 19 9 2 19 9 3 19 9 4 19 9 5 19 9 6 19 9 7

DEN-1 DEN-3 DEN-2

epidemics. 1. Chassaniol DMP. (1885). Lettre de Mr. Le Chef de Service de la Santé à Mr. Le Acknowledgments Directeur de l'Intérieur. Bull. Soc. Etudes Océaniennes-EFO, juin 1885; Numéro The authors thank C. Roche, O. spécial, 231, tome XIX (8): 218. Cassar, F. Laur, A. Babinet, K. Laille 2. Buisson. Les Marquises et les marquisiens. and JF Schnee for their collaboration, Ann Hyg Colon, 1903; 6: 535-551. Hodée P. and D.Q. Ha of Pasteur Institute, Ho In : Archevéché de Papeete (Ed) Tahiti 1834- Chi Minh City and M. Laille from 1984, 150 ans de vie chrétienne en église. Saint-Paul, Paris/Fribourg 1983. Institut Pasteur de Nouvelle Calédonie 3. Rosen L. Dengue antibodies in residents of for providing the 1996 virus strains. the , French . Am J The authors also thank N. Maruhi and Trop Med Hyg, 1958; 7: 403-405.

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4. Laigret J, Rosen L, Scholammer G. Sur une 12. Chungue E, Marché G, Plichart R. Comparison épidémie de Dengue survenue à Tahiti en of immunoglobulin G enzyme-linked 1964. Relations avec les "Fièvres immunosorbent assay (IgG-ELISA) and Hémorragiques" du Sud-Est Asiatique. Bull haemagglutination inhibition (HI) test for the Soc Path Exot, 1967; 60: 339-353. detection of Dengue antibodies. Prevalence of Dengue IgG-ELISA antibodies in Tahiti. Trans 5. Saugrain J, Rosen L, Outin-Fabre D, Moreau J- Roy Soc Trop Med Hyg, 1989; 83: 708-711. P. Une récente épidémie d'arbovirose du type 13. Rosen L, Rozeboom LE, Sweet BH, Sabin AB. Dengue à Tahiti. Comparaison avec The transmission of Dengue by Aedes l'épidémie de 1964. Bull Soc Path Exot, 1970; polynesiensis marks. Am J Trop Med Hyg, 63: 631-41. 1954; 3: 878-882. 6. Moreau J-P, Rosen L, Saugrain J, Lagraulet J. 14. Hargrave WW. Report of Dengue epidemic in An epidemic of Dengue on Tahiti associated . US Nav Med Bull, 1931; 29: with hemorrhagic manifestations. Am J Trop 565-572. Med Hyg, 1973; 22: 237-241. 15. Mumford EP, Mohr JL. Manual of the 7. Kaueffer H, Pichon G, Merlin M, et al. A distribution of communicable diseases and propos d'une épidémie contrôlée de Dengue their vectors in the tropics. Pacific Islands en Polynésie Française. Méd Trop, 1976; 36: Section-Part I, 26 pp ; Suppl. to Am J Trop 455-459. Med Hyg, 1944; 24.

8. Parc F, Tetaria C, Pichon G, et al. La Dengue 16. Séchan Y, Lardeux F, Loncke S. Les due au virus de type 4 en Polynésie Française. arthropodes vecteurs de maladies agents de nuisances. In : ORSTOM (ed.) Atlas de II. – Observations biologiques préliminaires Polynésie Française, 1993, Planche 58. sur quelques points précis d’épidémiologie et

de physiopathologie. Méd Trop, 1981; 41: 17. Fages J, Pichon G. Dengue and urbanization 97-102. in French Polynesia. Pacific Science Association, Honolulu, Hawaii, 1975; 281- 9. Chungue E, Laudon F, Glaziou P. Dengue and 286. Dengue haemorrhagic fever in French 18. Gubler DJ. Aedes aegypti and Aedes aegypti- Polynesia - current situation. Trop Med, borne disease control in the 1990s: top down 1993; 35: 209-215. or bottom up. Am J Trop Med Hyg, 1989; 40: 10. Chungue E, Burucoa C, Boutin J-P. Dengue 1 571-578. epidemic in French Polynesia, 1988-1989: 19. Lyon M-F. Epidémiologie de la Dengue dans surveillance and clinical, epidemiological, la région du Pacifique Sud. Thèse, Doctorat virological and serological findings in 1752 en Médecine, Faculté de Médecine, Paris documented clinical cases. Trans Roy Soc Trop 1980. Med Hyg, 1992; 86: 193-197. 20. Chungue E, Spiegel A, Roux J. DEN-3 in 11. Chungue E, Glaziou P, Spiegel A. Estimation French Polynesia: preliminary data. J Med of Dengue infection attack rate in a cohort of Aust, 1990; 152: 557-558. children during a DEN-3 outbreak in Tahiti. Southeast Asean J Trop Med Public Health, 21. Halstead SB. Antibody, macrophages, dengue 1992; 23: 157-158. virus infection, shock, and hemorrhage: a

92 Dengue Bulletin – Vol 22, 1998 Dengue in French Polynesia: Major Features, Surveillance, Molecular Epidemiology and Current Situation

pathogenetic cascade. Rev Infect Dis, 1989; épidémiologique de la dengue en 1996. 11, supp. 4: S830-S839. Bises, 1997; 2: 5-8. 22. Glaziou P, Chungue E, Gestas P. Dengue fever 28. Chungue, E. Molecular epidemiology of and dengue shock syndrome in French dengue viruses. In : Saluzzo JF, Dodet B (eds) Polynesia. Southeast Asian J Trop Med Public Factors in the Emergence of arbovirus Health, 1992; 23: 531-532. diseases. Elsevier, 1997; pp 93-101. 23. Knudsen AB. Global strategy for the 29. Rico-Hesse R. Molecular evolution of dengue prevention and control of dengue and dengue serotype 1 and 2 in nature. Virol, 1990; 174: haemorrhagic fever. In : Saluzzo JF, Dodet B 479-493. (eds) Factors in the emergence of arbovirus 30. Deubel V, Nogueira R, Drouet MT. Direct diseases. Elsevier, 1997; pp 131-140. sequencing of genomic cDNA fragments 24. Chungue E, Roche C, Lefevre M-F, Barbazan amplified by the polymerase chain reaction P, Chanteau S. Ultra-rapid, simple, sensitive, for molecular epidemiology of Dengue-2 and economical silica method for extraction viruses. Arch Virol, 1993; 129: 197-210. of dengue viral RNA from clinical specimens 31. Chungue E, Cassar O, Drouet MT. Molecular and mosquitoes by reverse transcriptase- epidemiology of Dengue-1 and Dengue-4 polymerase chain reaction. J Med Virol, 1993; viruses. J Gen Virol, 1995; 76: 1877-1884. 40: 142-145. 32. Guzman MG, Deubel V, Pelegrino JL. Partial

25. Chan KL, Ng SK, Chew LM. The 1973 dengue nucleotide and amino acid sequences of the haemorrhagic fever outbreak in Singapore enveloppe/nonstructural protein-1 gene and its control. Sing Med J, 1977; 18: 81-93. junction of four Dengue-2 virus strains 26. Chungue E, Boutin J-P, Roux J. Dengue isolated during the 1981 Cuban epidemic. surveillance in French Polynesia: an attempt Am J Trop Med Hyg, 1995; 52: 241-246. to use the excess number of laboratory 33. Chungue E, Deubel V, Cassar O. Molecular requests for confirmation of Dengue epidemiology of DEN-3 viruses and genetic diagnosis as an indicator of dengue activity. relatedness among DEN-3 strains isolated Eur J Epidemiol, 1991; 7: 616-620. from patients with mild or severe form of 27. Deparis X, Chungue E, Murgue B. Bilan du Dengue fever in French Polynesia. J Gen Virol, réseau sentinelle de surveillance 1993; 74: 2765-2.

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