Description of an outbreak of hemorrhagic fever with renal syndrome in the southern Jura Mountains, France, in 2021.

OBJECTIVE: The aim of our study was to describe the 2021 Hemorrhagic Fever with Renal Syndrome (HFRS) outbreak in the southern Jura Mountains. PATIENTS AND METHODS: We included all laboratory-confirmed cases of HFRS reported between April and September 2021 in the three local hospitals. RESULTS: A total of 90 patients were enrolled in the study: 73 hospitalized and 17 non-hospitalized patients. Transient myopia was only reported in non-hospitalized patients. Forty (44.4 %) patients underwent medical imaging before hantavirus diagnosis. Twenty-one patients (28.8 %) had a plasma creatinine level > 353.6 µmol/L, no patient developed severe metabolic disorder. Only one patient was dialyzed. A pacemaker was implanted before diagnosis of HFRS due to severe bradycardia in one patient. Sudden death was reported in one patient. CONCLUSION: This hantavirus epidemic led to numerous hospitalizations, one dialysis treatment, and one death. Early diagnosis by rapid test could avoid unnecessary investigations.

Sporadic cases of chikungunya, Réunion Island, August 2009.

On 28 August 2009, French authorities reported five cases of chikungunya fever on Reunion Island: three confirmed, one probable, and one suspected case under investigation. All three confirmed patients presented with an acute febrile syndrome, arthralgia, myalgia and cutaneaous rash. All live in the same area on the western side of the island.

IL-10-producing T cells suppress immune responses in anergic tuberculosis patients.

The lethality of Mycobacterium tuberculosis remains the highest among infectious organisms and is linked to inadequate immune response of the host. Containment and cure of tuberculosis requires an effective cell-mediated immune response, and the absence, during active tuberculosis infection, of delayed-type hypersensitivity (DTH) responses to mycobacterial antigens, defined as anergy, is associated with poor clinical outcome. To investigate the biochemical events associated with this anergy, we screened 206 patients with pulmonary tuberculosis and identified anergic patients by their lack of dermal reactivity to tuberculin purified protein derivative (PPD). In vitro stimulation of T cells with PPD induced production of IL-10, IFN-gamma, and proliferation in PPD(+) patients, whereas cells from anergic patients produced IL-10 but not IFN-gamma and failed to proliferate in response to this treatment. Moreover, in anergic patients IL-10-producing T cells were constitutively present, and T-cell receptor-mediated (TCR-mediated) stimulation resulted in defective phosphorylation of TCRzeta and defective activation of ZAP-70 and MAPK. These results show that T-cell anergy can be induced by antigen in vivo in the intact human host and provide new insights into mechanisms by which M. tuberculosis escapes immune surveillance.

Endotheliotropic elephant herpes virus (EEHV) infection. The first PCR-confirmed fatal case in Asia.

Since 1995, 4 suspected cases of Endotheliotropic Elephant Herpes Virus (EEHV) infection, i.e. based on clinical presentation, have occurred in Asia without resulting in epidemic outbreaks as expected. In order to confirm the presence of EEHV on the continent of Asia, viral DNA particles from liver samples of a wild-caught 3-year-old elephant found dead at a Cambodian elephant sanctuary and clinically diagnosed with EEHV, were PCR processed using known EEHV strain primers. The presence of EEHV viral nucleic acids was confirmed and the nucleic acids had a 99% sequence similarity to the U.S.A strain (gene bank locus: AF117265) and 97% sequence similarity to the European strain (gene bank locus: AF354746) assigning this case to the EEHV-1 cluster. More than the confirmation of EEHV on the continent of Asia, is the phylogenic relationship to the USA and European strains with no corresponding contact or transport of USA or European elephants to Asia. Thus, this brings many of the traditional theories into question. Although almost forgotten, this disease is still ramped in captive elephant populations worldwide and continues to devastate particularly the neonatal and weaning-age population. Special attention and continued research are needed specifically in the area of basic virology and epidemiology.

[Seoul hantavirus infection-associated hemorrhagic fever with renal syndrome in France: A case report]. / Fièvre hémorragique à syndrome rénal associée à l'hantavirus Séoul en France : une observation.

INTRODUCTION: Rodents are hantavirus hosts. In Europe, hantaviruses are responsible for human infections resulting in hemorrhagic fever with renal syndrome. Thousands of Puumala virus infections are reported annually in Europe, whereas human Seoul virus infections are rarely detected. CASE REPORT: We report the case of a 38-year-old patient who presented initially with flu-like symptoms and transitory blurred vision. He developed thrombocytopenia, acute renal failure, and elevated aminotransferases levels during the disease course, but the outcome was favorable with a full recovery. Afterwards, the hantavirus serology results were indicative of Seoul virus infection. CONCLUSION: This report serves to remind physicians to consider diagnosing hantavirus infection when observing the association of fever, acute renal failure and thrombocytopenia. Transitory blurred vision is a specific element to indicate this diagnosis.

The first epidemic of dengue hemorrhagic fever in French Guiana.

From July 1991 to October 1992, an outbreak of dengue spread into the main urban areas of French Guiana, where 90% of the country's 114,808 inhabitants live. In mid-July 1991 dengue-2 virus was identified as being responsible for most cases, while dengue-1 virus was rarely isolated and circulated at a low level. The number of dengue cases during this period was unknown because there was no clinically based dengue surveillance system. The only available data were for the number of suspected cases as indicated by the number of patients for whom blood samples were submitted to a laboratory for dengue diagnosis. Eight hundred forty-seven of the 2,948 suspected cases were diagnosed in the laboratory as dengue cases. Six fatal cases were reported. This outbreak was marked by the appearance of the first clinical cases of dengue hemorrhagic fever (DHF) in French Guiana. Forty cases met the World Health Organization definition of clinical DHF: 32 were grade II, seven were grade III, and one was grade IV and fatal. Eighteen cases were confirmed in the laboratory and 12 were probable; there was no proof of the dengue etiology for the remaining patients.

Plasmodium falciparum parasites in French Guiana: limited genetic diversity and high selfing rate.

The genetic characteristics of Plasmodium falciparum isolates collected in French Guiana, where malaria transmission is low and occurs in isolated foci, were studied. Blood samples were collected from 142 patients with symptomatic malaria and typed using a polymerase chain reaction-based strategy for merozoite surface protein-(MSP-1) block 2, the MSP-2 central domain, and glutamate-rich protein (GLURP) repeat domain polymorphism. This showed that the parasite population circulating in French Guiana presented a limited number of allelic forms (4, 2, and 3 for MSP-1 block 2, MSP-1, and GLURP, respectively) and a small number of mixed infections, contrasting with the large genetic diversity of parasite populations and infection complexity reported for Africa, Asia, and other parts of South America. Two groups of isolates displaying identical 3 loci allele combinations were further studied for the Pf332 antigen, histidine-rich protein-1, thrombospondin-related anonymous protein, and Pf60 multigene family polymorphism. Within each group, most isolates were identical for all markers tested. This suggests a high rate of self-fertilization of P. falciparum parasites in French Guiana, resulting in homogenization of the population. The implications of these findings for malaria control in areas of low endemicity are discussed.

Fleas in French Guiana (Insecta: Siphonaptera).

Based on a collection of approximately 760 fleas, of which 520 were collected in 1994-1995 during scientific studies at the Petit Saut dam site in French Guiana, 12 species and subspecies are discussed. Two taxa, Rhopalopsyllus garbei Guimarães, 1940 and Adoratopsylla intermedia copha (Jordan, 1926), are new records for French Guiana. The fleas collected during the 1994-1995 study were obtained from 35 species of mammals (3,484 specimens); of which, 21 (60%) species were negative for fleas. The mammals were captured primarily by live-trapping during a capture-release study along a portion of the Sinnamary River and its tributaries up to a distance of 70 km upstream from the Petit Saut dam site.

Characterization and observation of animals responsible for rabies post-exposure treatment in Phnom Penh, Cambodia.

In order to provide relevant therapeutic answers to human patients exposed to risk of rabies infection who visit the Institut Pasteur du Cambodge for post-exposure treatment and to improve control of rabies in Cambodia, a pilot study was carried out in Phnom Penh Province in November and December 1997 with three objectives: characterization of the population of animals responsible for the exposure to rabies, observation of the animals concerned, and confirmation of the presence of rabies virus in the province. Between 18 November 1997 and 19 December 1997, 409 of the 741 patients treated at the Institut Pasteur du Cambodge because of an exposure to a known rabies vector were included in the study. The animals concerned were: 401 dogs (98%), six monkeys (1.5%) and two cats (0.5%). Three-hundred-and-seventy of the animals (90.5%) were owned, 4 (1%) were unowned but were available for characterization and observation, and 35 (8.6%) had an unknown ownership status and were not available for further study. The exposures occurred on private property in 84% of the cases, and 80 of the 370 owned animals (22%) lived in the same home as had the patient. The 374 animals with known ownership status were examined. Five were already dead and two of these five dogs had presented clinical signs typical of those of rabies. The male:female sex ratio of the dogs was 2.1:1. The 369 live animals were placed under observation for 10 d immediately after exposure of the humans had taken place. At the end of the period none of the animals had developed clinical signs of rabies, three had died of diseases other than rabies, and one was lost. Tests for the rabies nucleocapsid antigen were positive in two cases (the two suspected rabid dogs), confirming the presence of rabies in Phnom Penh Province. Consequently, we recommend measures to improve the control of rabies in Cambodia.

[Dengue in French Guiana. History and present status]. / La dengue en Guyane Française. Historique et actualités.

The evolution of dengue in French Guiana has the same trend as in most tropical American countries, with emergence of dengue hemorrhagic fever (DHF) and endemicity of the disease. During the 1940's, several dengue-like outbreaks were reported from French Guiana. Then, the only dengue vector, Aedes aegypti, was eradicated between 1950 and 1963, when it started to reinfest the country. By the end of the 1960's, new dengue epidemics with serological confirmation were described. After 1970, the first dengue strains were isolated, firstly dengue-2 strains, then dengue-1 and dengue-4 strains. Between 1970 and 1990, several dengue outbreaks struck French Guiana with 2 to 6 years intervals. In July 1991, started the first DHF outbreak in French Guiana which spread in all the most important towns until October 1992. About 3,000 cases were reported, that is almost 3% of the population, from which about 1/3 had serological confirmation; more than 300 people were hospitalized and some 80 with hemorrhages. Finally 6 deaths were reported, 5 of which had hemorrhages but could not be included into DHF cases according to WHO criteria. The dengue-2 strain responsible for this outbreak is close to the Jamaïcan topotype known to be particularly virulent. Since the beginning of 1993 and actually, dengue is still circulating in French Guiana, but at low level and dengue-1 and dengue-4 strains are occasionally isolated.

[Current situation of yellow fever in Latin America]. / Situation actuelle de la fièvre jaune en Amérique latine.

Yellow fever endemicity is currently stabilized in South America: an average of 115 cases has officially been notified each year since 25 years (between 12 and 304 annual cases). These figures are underevaluated but no epidemic has been observed since 1983. Only sporadic or limited grouped cases have been reported. All declared cases correspond to people who have been infected within sylvatic areas, mainly adult forestmen. Within the last years, the majority of cases have occurred in Peru and Bolivia; the other cases have been observed in Brazil, in Columbia, in Ecuador and in French Guiana (imported strains from Surinam). This apparently low virus circulation may be due to massive campaigns of vaccination and to mosquito vector control. But this situation could suddenly reverse as observed in the past with yellow fever and the spring of the urban Aedes aegypti vector. Genetic and immunochemical heterogeneity has been demonstrated between South American and African yellow fever strains, which may reveal evolutionary divergence due to different ecological environment between the two continents. Yellow fever definitely remains a topical disease which requires a constant surveillance.

HIV-1 gp41-specific monoclonal mucosal IgAs derived from highly exposed but IgG-seronegative individuals block HIV-1 epithelial transcytosis and neutralize CD4(+) cell infection: an IgA gene and functional analysis.

AIDS is mainly a sexually transmitted disease, and accordingly, mucosal tissues are the primary sites of natural human immunodeficiency virus type-1 (HIV-1) transmission. Mucosal immunoglobulin A (IgA) antibody specific for HIV-1 envelope gp41 subunit is one correlate of protection in individuals who are highly sexually exposed to HIV-1 but remain persistently IgG seronegative (HEPS). Understanding these peculiar IgAs at the gene and functional level is possible only with monoclonal IgAs. We have constructed a mucosal Fab IgA library from HEPS and have characterized a series of HIV-1 IgAs specific for gp41 that, in vitro, are transcytosis-blocking and infection-neutralizing. Characterization of their IgA genes shows that Fab specific for the gp41 membrane-proximal region harbors a long heavy-chain CDR3 loop (CDRH3) similar to the two broadly neutralizing IgG monoclonal antibodies, 2F5 and 4E10. Furthermore, the selected Fab IgA shows extensive somatic mutations that cluster in the CDR regions, indicating that affinity maturation due to an antigen-driven process had occurred in HEPS individuals, presumably upon multiple exposures to HIV. This analysis of HEPS monoclonal IgA gives a unique opportunity to correlate an antibody function (resistance to a pathogen in vivo) with an antibody gene. Such neutralizing monoclonal IgAs could be used in microbicide formulation.

Factors influencing the population structure of Aedes aegypti from the main cities in Cambodia.

A population genetic analysis was conducted on 47 Aedes aegypti collections from Cambodia. Genetic differentiation at seven polymorphic isoenzyme loci was analysed by starch gel electrophoresis. Low (F(ST)=0.024) but significant (P<10(-6)) differentiation was found when all samples were considered. Whatever the grouping of samples tested, differentiation remained significant but low. The role of human activities (ie insecticide treatments or water storage practices) and environmental factors (ie rainfall) in shaping mosquito differentiation are discussed.

Frequent infection of Hylobates pileatus (pileated gibbon) with species-associated variants of hepatitis B virus in Cambodia.

As well as being distributed widely in human populations, hepatitis B virus (HBV) infections occur frequently in chimpanzee, gibbon and other ape populations in sub-Saharan Africa and South-East Asia. To investigate the frequency and genetic relationships of HBV infecting gibbons in Cambodia, pileated gibbons (Hylobates pileatus) that were originally wild-caught were screened for surface antigen. Twelve of 26 (46 %) were positive, of which 11 were positive for HBV DNA. Phylogenetic analysis of complete genome sequences revealed two distinct genetic groups in the gibbon/orangutan clade. Three were similar to previously described variants infecting H. pileatus in Thailand and eight formed a distinct clade, potentially representing distinct strains of HBV circulating in geographically separated populations in South-East Asia. Because of the ability of HBV to cross species barriers, large reservoirs of infection in gibbons may hamper ongoing attempts at permanent eradication of HBV infection from human populations in South-East Asia through immunization.

Dengue in French Guiana, 1965-1993.

While it seems likely that dengue fever (DF) has existed in French Guiana for at least one century, data on outbreaks are sketchy before temporary eradication of the dengue vector mosquito Aedes aegypti and its reestablishment in the early 1960s. Dengue cases were serologically confirmed for the first time in 1965, and since then dengue epidemics have occurred at two to six year intervals, the most important occurring in 1968-1969, 1970, 1972, 1976, 1982, 1986, and 1992. Three of the four dengue virus serotypes (dengue-1, dengue-2, and dengue-4) have been implicated in these outbreaks. During the 1992 epidemic, which appears to have begun in 1991 and extended into 1993, cases of dengue hemorrhagic fever (DHF) were confirmed for the first time. In all, at least 40 DHF cases and several deaths were associated with this epidemic. This development has raised considerable concern about the public health threat posed by DHF in French Guiana. Such concern is only heightened by the fact that while vector control is the sole means of preventing or combating dengue outbreaks, it has proved difficult to maintain vector populations at low levels with the control measures currently employed.