Xavier Deparis

Prospective study of the duration and magnitude of viraemia in children hospitalised during the 1996-1997 dengue-2 outbreak in French Polynesia.

The magnitude and duration of viraemia in children admitted to the hospital with dengue was studied during a dengue 2 outbreak in French Polynesia in 1996–1997. Forty‐nine patients from whom at least 3 plasma samples were available were included in the study. Based on analysis of IgG‐ELISA and haemagglutination inhibition assay, 21 of these were primary and 28 were secondary infections. According to World Health Organization criteria, 42 were dengue fever and 7 were dengue haemorrhagic fever. Virus was detectable by reverse transcription‐PCR in all patients for at least the first 3 days of the onset of fever, but was never detected after the 6th day (mean duration = 4.4 days). Plasma virus titers ranged from 1.7–5.6 Log10 TCID50/ml. A significant difference was not observed in the magnitude and duration of viraemia in patients with primary versus secondary infections. The severity of the illness, however, was correlated with both criteria. J. Med. Virol. 60:432–438, 2000.

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

Summary 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.

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.

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

Abstract 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 α (TNFα) and transforming growth factor β-1 (TGFβ-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 TNFα. By contrast, plasma obtained from children with DHF had significantly higher levels of TGFβ-1 than plasma from children with DF, especially from days 1 to 3 after the onset of fever.

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.

IMPLICATION OF MACROPHAGE INFLAMMATORY PROTEIN-1ALPHA IN THE INHIBITION OF HUMAN HAEMATOPOIETIC PROGENITOR GROWTH BY DENGUE VIRUS

The mechanisms were investigated of haematopoietic progenitor growth inhibition, observed after in vitro infection of cord blood mononuclear cells (CBMNC) by a clinical isolate of dengue 3 (29-56DSS). The level of virus replication was not different when CBMNC were inoculated with 29-56DSS compared with a prototype strain of dengue 3 (H-87) which had no inhibitory effect. An inhibitory effect was also observed when cell-free and heat-inactivated supernatants from 29-56DSS cultures, but not from H-87 cultures, were added to cultures of normal CBMNC, suggesting an indirect mechanism via the release of soluble suppressive factor(s). Macrophage inflammatory protein-1alpha (MIP-1alpha) was detected at a significantly higher level in 29-56DSS cultures than in controls. Blocking experiments with anti-MIP-1alpha antibody demonstrated that the inhibitory effect was related at least partly to high MIP-1alpha levels. To our knowledge, this is the first report suggesting an indirect effect of dengue infection on haematopoiesis mediated by a suppressive cytokine.