Hantavirus infections in Ile-de-France

Hantavirus infections, Puumala serotype, is a well-known disease in the northeast of France, but not in the Paris area, despite regularly diagnosed cases. A retrospective study was performed from January 1999 to December 2000 to assess the clinical and epidemiological characteristics of this disease in the "Région Ile-de-France". Fourteen cases were diagnosed. All required hospitalisation. Patients presented usually with high fever, pain, renal failure, moderate thrombocytopenia and, sometimes, transitional acute myopia witch is pathognomonic of the disease. In each case, a contact with a forest was found. Twelve patients recovered completely. One patient with pre-existing chronic renal and hepatic failure died and another developed a persistent arterial hypertension. Invasive procedures were often used before the diagnosis. Hantavirus infections does exist in the "Région Ile-de-France". Failure to recognise this disease in this area lead to unnecessary invasive procedures and hospitalizations.     

Possible dengue sequential infection: dengue spread in a neighbourhood during the 1996/97 dengue-2 epidemic in French Polynesia

A DEN-2 epidemic occurred in French Polynesia from August 1996 to April 1997 after 7 years of DEN-3 circulation. The susceptible population constituted all expatriates and Polynesians under 21. In August 1996, two successive DEN-2 cases occurred in Teroma, a Tahitian neighbourhood close to the international airport of Tahiti. A serological prospective study of persons < 21 years living in Teroma was conducted. The study population was bled in September 1996, October 1996 and June 1997. Analysis of dengue spread in Teroma confirmed that dengue transmission occurs primarily in the house, thus vector control campaigns should incorporate focal insecticide spraying and systematic daily use of insecticide in houses. The evolution in time of the disease demonstrated that among a susceptible population, prevalence and incidence rates are related to the time of exposure, and consequently to age. Comparison of dengue incidence or dengue prevalence between populations therefore requires adjusted age rates. Most studies did not adjust for age, leading to the conclusion that DHF is more frequent during secondary than during primary dengue infection. Prospective studies taking into account the time of dengue exposure are necessary to confirm the sequential infection hypothesis.     

Surveillance épidémiologique specifique de la dengue: Méthode et intérêt lors de l'épidémie de dengue 2 en Polynésie française en 1996

La dengue est une arbovirose présente dans toute la zone intertropicale. Son extension géographique et l'augmentation simultanée de sa létalité sont préoccupantes. En zone d'endémie ou d'épidémie, une surveillance épidémiologique spécifique de la dengue permet d'identifier et de confirmer au plus vite la circulation d'un nouveau sérotype viral de la dengue: avec un délai d'alerte épidémique raccourci, l'efficacité des stratégies de lutte est renforcée. En Polynésie française, alors que seul le sérotype 3 circulait depuis 1989, la menace d'une épidémie de dengue 4 a déclenché la mise en place d'une surveillance épidémiologique spécifique en mai 1996. Devant chaque cas suspect de dengue, 18 médecins répartis sur le territoire polynésien effectuaient un prélèvement sanguin et rédigeaient une fiche de renseignements cliniques. Entre mai et novembre 1996, le laboratoire de virologie de l'Institut Malardé a mis en évidence 21 virus (2 de dengue 3 et 19 de dengue 2) soit par mise en culture, soit par RT-PCR, sur les 302 prélèvements traités. La surveillance spécifique a démontré la circulation d'un virus dengue 2 et elle a permis de raccourcir de 12 à 16 semaines le délai d'alerte épidémiologique par rapport aux précédentes épidémies. Tenant compte du délai de prélèvement, une régression logistique effectuée sur les variables cliniques a montré que seule l'absence de toux était prédictive de la dengue. Construits autour d'objectifs pragmatiques, la performance des systèmes épidémiologiques de surveillance spécifique de la dengue doit encourager leur mise en ?uvre dans tous les pays concernés, en passant, si nécessaire, par une collaboration avec des laboratoires de référence. Dengue fever is present in tropical and subtropical regions and its geographical extension and the simultaneous increase of its mortality are worrisome. In endemic or epidemic countries, the aim of dengue-specific epidemiological surveillance is to confirm as soon as possible the circulation of a new viral dengue serotype, i.e. the beginning of an epidemic. The efficiency of the control strategy is improved by an earlier epidemic alert. In French Polynesia, dengue-3 virus circulated since 1989 at low level and, in May 1996, a specific epidemiological surveillance was undertaken because of the threat of a dengue-4 epidemic. From each suspected dengue case reported by 18 Polynesian physicians located in the Société Islands, a blood sample was taken for virological assay and clinical data were reported. Between May and November 1996, the virology unit of the Institut Malardé isolated 21 viruses (2 dengue-3 and 19 dengue-2) from 302 suspected cases. The dengue-specific epidemiological surveillance confirmed that dengue-2 virus was circulating and reduced the time of the epidemiological alert by 2 or 3 months compared to previous epidemics. Taking into account the day of illness, a logistic regression undertaken on the clinical data showed that the absence of cough was the only predictive sign of dengue diagnosis. The performance of this dengue-specific epidemiological surveillance system led us to consider its implementation in all concerned countries. A collaboration with international reference laboratories could be a solution for the developing countries.     

West Nile virus outbreak in horses,southern France, 2000: results of a serosurvey

During late summer and autumn 2000, a West Nile fever outbreak in southern France resulted in 76 equine clinical cases; 21 horses died. We report the results of a large serosurvey of all equines within a 10-km radius of laboratory-confirmed cases. Blood samples were obtained from 5,107 equines, distributed in groups of 1 to 91 animals. West Nile virus immunoglobulin (Ig) G antibodies were found in 8.5% of animals (n=432). Forty-two percent of the IgG-positive animals were also IgM positive. Horses living in small groups were more affected than those in large groups. The results suggest that West Nile virus is not endemic in the affected area, the Camargue; rather, sporadic outbreaks are separated by long silent periods.     

Plasma concentrations of sVCAM-1 and severity of dengue infections

Adhesion molecules are essential for the immune response. They are involved in the regulation of cell-to-cell contact, thereby enabling leukocytes to communicate. Circulating forms of adhesion molecules are found in the serum of healthy individuals. Raised levels have been associated with disease severity in HCV and other infections and thus appear to be good markers of endothelial damage. The levels of soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) and of sP and sL-selectin in the plasma of children hospitalised for dengue in French Polynesia were monitored. Studies from the 1996/1997 dengue-2 outbreak, showed that levels of sVCAM-1 increase steadily during the febrile period, peak on day 7, and then decline relatively rapidly. Disregarding the time frame within the febrile period, sVCAM-1 levels were always higher compared to controls. There was a significant association between sVCAM-1 levels and dengue haemorrhagic fever, a severe manifestation of dengue virus infection characterised by plasma leakage. No association was apparent between sVCAM-1 levels and primary vs. secondary dengue virus infections. Levels of sP-selectin and sL-selectin were significantly higher in primary compared with secondary infection but were not different in patients presenting with plasma leakage. Lastly, sVCAM-1 levels were significantly higher in an outbreak of severe disease in 1989/1990 (dengue-3) when compared to a non-severe outbreak in 1988/1989 (dengue-1) and a mild outbreak in 1996/1997 (dengue-2). The results suggested that levels of sVCAM-1 production might prove to be a useful marker in the management of severe dengue.     

Changing clinical and biological manifestations of dengue during the dengue-2 epidemic in French Polynesia in 1996/97 – description and analysis in a prospective study

In August 1996 dengue-2 virus was detected in French Polynesia for the first time since 1976. A prospective study was conducted from November 1996 to April 1997. Each time one of 7 physicians suspected dengue, the patient was enrolled and epidemiological, clinical and biological data were recorded. Dengue diagnosis was confirmed by virus isolation and IgM detection. The aims of this study were to find clinical and biological predictive factors constituting a specific profile of dengue (DF) and dengue haemorrhagic fever (DHF/DSS) and to assess the possibility of diagnosing dengue at primary health care level using clinical criteria and basic laboratory parameters. Of 298 clinically suspect cases, 196 (66%) were confirmed as dengue. The association of macular rash, pruritis, low platelet count and leukopenia was statistically predictive of dengue but not clinically, since these four signs occur in many other viral infections. As the prevalence of clinical and biological manifestations varied over time in our study, a specific profile useful for dengue diagnosis cannot be defined. With six cases of DHF, the morbidity of this dengue-2 outbreak was very low despite the sequential infection scheme DEN-3/DEN-2. The clinical expression of dengue could depend on a specific virus strain circulating in a specific population in a particular place, with varying virulence over time.     

Dengue: an evaluation of dengue severity in French Polynesia based on an analysis of 403 laboratory-confirmed cases

We conducted a retrospective study of 403 laboratory-confirmed dengue cases hospitalized in Tahiti between August 1989 and March 1997. According to standard WHO criteria, 337 of these cases were dengue fever (DF) and 64 were dengue haemorrhagic fever (DHF). Of the 10 fatal cases, 6 were DF and 4 were DHF. As an alternative, we used a correspondence analysis procedure to define dengue severity based on basic clinical and biological criteria for which we assigned a severity score, and then selected the 50 most severe cases from this analysis. Of the latter, 17 patients had been classified as DF and 33 as DHF by the WHO criteria. From this analysis, haemorrhages and decreased platelets counts associated with hepatic disorders are the main criteria associated with the severe dengue cases. Thus in our study population, the WHO classification does not account for the overall severity of dengue; hepatic failure should be considered as a specific severe form of dengue since plasma leakage, which is the pathophysiological hallmark of DHF, is only one of the pathogenic mechanisms leading to severity.     

Plasma levels of tumour necrosis factor alpha and transforming growth factor beta-1 in children with dengue 2 virus infection in French Polynesia.

The pathogenesis of dengue haemorrhagic fever (DHF) is not well understood. In the absence of predictive clinical or biological criteria, the management of DHF patients remains difficult. The role played by cytokines in the occurrence of DHF has been suggested by several authors. In this study, we determined the plasma levels of tumour necrosis factor alpha (TNF alpha) and transforming growth factor beta-1 (TGF beta-1) in 52 children with laboratory-confirmed dengue virus infection admitted to hospital during the recent dengue 2 outbreak in French Polynesia. Thirty-three children were classified as having dengue fever (DF) and 19 as DHF. The plasma of both DF and DHF patients contained similar levels of TNF alpha. By contrast, plasma obtained from children with DHF had significantly higher levels of TGF beta-1 than plasma from children with DF, especially from days 1 to 3 after the onset of fever.