[West Nile viral meningo-encephalitis in Tunisia]. / Méningo-encéphalite à arbovirus West Nile en Tunisie.

In autumn 1997 an epidemic outbreak of meningoencephalitis was observed in two coastal districts of Tunisia. A total of 173 cases were recorded with 8 deaths. Detection with IgM capture and indirect IgG ELISAs demonstrated West Nile virus infection in 86% of patients from whom specimens were collected. West Nile is endemic in Asia and Sub-Saharan Africa. Epidemics in humans and horses have also been reported in the Mediterranean region and southern European countries. However this is the first report in Tunisia. Special West Nile virus surveillance is necessary especially in countries at high-risk for repeated introduction of this arbovirus.

Human infection due to Ebola virus, subtype Côte d'Ivoire: clinical and biologic presentation.

In November 1994 after 15 years of epidemiologic silence, Ebola virus reemerged in Africa and, for the first time, in West Africa. In Côte d'Ivoire, a 34-year-old female ethologist was infected while conducting a necropsy on a wild chimpanzee. Eight days later, the patient developed a syndrome that did not respond to antimalarial drugs and was characterized by high fever, headache, chills, myalgia, and cough. The patient had abdominal pain, diarrhea, vomiting, and a macular rash, and was repatriated to Switzerland. The patient suffered from prostration and weight loss but recovered without sequelae. Laboratory findings included aspartate aminotransferase and alanine aminotransferase activity highly elevated, thrombocytopenia, lymphopenia, and, subsequently, neutrophilia. A new subtype of Ebola was isolated from the patient's blood on days 4 and 8. No serologic conversion was detected among contact persons in Côte d'Ivoire (n = 22) or Switzerland (n = 52), suggesting that infection-control precautions were satisfactory.

Histopathological and immunohistochemical studies of lesions associated with Ebola virus in a naturally infected chimpanzee.

Lesions caused by the Côte d'Ivoire subtype of Ebola virus in a naturally infected young chimpanzee were characterized by histopathological and immunohistochemical methods. The predominant lesions consisted of multifocal necrosis in the liver and diffuse fibrinoid necrosis in the red pulp of the spleen. In these sites, macrophages contained large eosinophilic intracytoplasmic inclusion bodies. Immunohistochemical staining indicated that macrophages were a major site of viral replication. The absence of bronchiolar and pulmonary lesions and the paucity of antigen-containing macrophages in the lung suggested that aerosol transmission by this animal was unlikely. There were necrotic foci and antigen-containing macrophages in intestinal lymph nodes, in association with lesions caused by intestinal parasites, suggesting the possibility of virus entry through the digestive tract.

The reemergence of Ebola hemorrhagic fever, Democratic Republic of the Congo, 1995. Commission de Lutte contre les Epidémies à Kikwit.

In May 1995, an international team characterized and contained an outbreak of Ebola hemorrhagic fever (EHF) in Kikwit, Democratic Republic of the Congo. Active surveillance was instituted using several methods, including house-to-house search, review of hospital and dispensary logs, interview of health care personnel, retrospective contact tracing, and direct follow-up of suspect cases. In the field, a clinical case was defined as fever and hemorrhagic signs, fever plus contact with a case-patient, or fever plus at least 3 of 10 symptoms. A total of 315 cases of EHF, with an 81% case fatality, were identified, excluding 10 clinical cases with negative laboratory results. The earliest documented case-patient had onset on 6 January, and the last case-patient died on 16 July. Eighty cases (25%) occurred among health care workers. Two individuals may have been the source of infection for >50 cases. The outbreak was terminated by the initiation of barrier-nursing techniques, health education efforts, and rapid identification of cases.

Ebola virus outbreak among wild chimpanzees living in a rain forest of Côte d'Ivoire.

An outbreak of Ebola in nature is described for the first time. During a few weeks in November 1994, approximately 25% of 43 members of a wild chimpanzee community disappeared or were found dead in the Taï National Park, Côte d'Ivoire. A retrospective cohort study was done on the chimpanzee community. Laboratory procedures included histology, immunohistochemistry, bacteriology, and serology. Ebola-specific immunohistochemical staining was positive for autopsy tissue sections from 1 chimpanzee. Demographic, epidemiologic, and ecologic investigations were compatible with a point-source epidemic. Contact activities associated with a case (e.g., touching dead bodies or grooming) did not constitute significant risk factors, whereas consumption of meat did. The relative risk of meat consumption was 5.2 (95% confidence interval, 1.3-21.1). A similar outbreak occurred in November 1992 among the same community. A high mortality rate among apes tends to indicate that they are not the reservoir for the disease causing the illness. These points will have to be investigated by additional studies.

Recombinant Ebola virus nucleoprotein and glycoprotein (Gabon 94 strain) provide new tools for the detection of human infections.

After cloning and sequencing the glycoprotein (GP) gene of one of the Gabonese strains of Ebola virus isolated during the 1994-1996 outbreak, it was shown that the circulating virus was of the Zaire subtype. This was confirmed in this study by cloning and sequencing the nucleoprotein (NP) gene of this strain. These two structural proteins were also expressed as recombinant proteins and used in ELISA tests. NP was expressed as a His-tagged fusion protein in Escherichia coli and was purified on resins charged with nickel ions. GP was expressed by means of recombinant baculoviruses in Spodoptera frugiperda cells. Both recombinant proteins reacted positively in ELISAs for the detection of IgG antibodies in convalescent human sera from Gabon and Zaire. The difference in the relative titres of anti-NP and -GP antibodies was variable, depending on the sera. In addition, the recombinant NP reacted with heterologous sera from Côte d'Ivoire and was used successfully to detect IgM antibodies by mu-capture ELISA in sera from Gabonese patients.

[Hantavirus and pulmonary pathology]. / Hantavirus et pathologie pulmonaire.

The hantavirus pulmonary syndrome recognized in the United States in 1993 quickly brought the formerly little known virus into the limelight. Contrary to what has been written almost everywhere, this is not a "new" virus causing new "emerging" disease. Hantaviruses have been harbored in their natural hosts, three subfamilies of murine rodents, for millions of years. The phylogenetic classifications of these viruses follows that of their hosts, proving close adaptation and contradicting short-term emergence of American serotypes in Eurasia. Certain hantaviruses are the causal agents of renal diseases of variable severity grouped together under the term of hemorrhagic fever with a renal syndrome in Eurasia. Others cause acute respiratory distress syndrome, particularly in North America. Most cases occur in adults and the sex-ratio always favors men, probably due to exposure to airborne rodent ejections. No interhuman contamination is observed. A few dozen cases of hantavirus pulmonary syndrome are reported annually in North America and a few hundred cases in Europe. China is the only country were incidence has been high enough for hundreds of years to lead to an experimentation on vaccines. Hantaviruses are difficult to isolate and diagnosis in humans is based on serology. Improved diagnostic tools have led to a better assessment of the impact of this virus on public health. An epidemic in France in 1996 caused 230 cases while only 808 cases had been registered since 1977. Most of the cases occurred in Northeastern France and were focalized.

Molecular detection and characterization of yellow fever virus in blood and liver specimens of a non-vaccinated fatal human case.

A yellow fever virus of a South American genotype was identified in the liver and blood samples of a non-vaccinated European patient after his return from Brazil. ELISA tests were negative for IgG and positive for IgM against yellow fever. Yellow fever proteins in the formalin-fixed and paraffin-embedded liver biopsy were detected by immunohistochemical procedures. Viral RNA extracted from the liver tissue was also detected using an RT-semi-nested PCR procedure and molecular hybridization. Alignment of the sequence obtained from a gene fragment amplified by RT-semi-nested PCR directly from a blood sample with those of African and South American yellow fever virus strains identified a Brazilian topotype as being responsible for the disease. RT-semi-nested PCR may be used advantageously for clinical specimens for rapid and specific diagnosis, and with archival biopsy material for retrospective studies.

[Viral hemorrhagic fevers: what is the risk for travelers?]. / Les fièvres hémorragiques virales: quel risque pour le voyageur?

The term hemorrhagic fever covers a number of diseases with different clinical and epidemiologic features. All these diseases are zoonoses but their occurrence is not confined to tropical areas. Some occur in polar zones. Travelers to endemic areas for these diseases are at risk of infection. There are two modes of transmission. Arthropods are vectors for some diseases such as yellow fever, dengue fever, and Rift Valley fever which are carried by mosquitos and Congo-Crimea virus which is carried by ticks. Airborne contamination by rodent excrement is responsible for transmission of hantaviruses and arenaviruses. Nosocomial infection is a risk for health care providers. Some types of hemorrhagic fever such as Bolivian hemorrhagic fever are highly localized, while other types such as dengue are observed worldwide. Judging from the small number of cases observed in European countries, the overall risk for travelers seems low except unless high-risk activities are planned. The main exceptions are yellow fever and dengue which can easily be transmitted to tourists by mosquitos. Yellow fever can be prevented by vaccination. Typical dengue is usually self-limited but hemorrhagic forms require treatment to prevent shock.

Haemorrhagic fevers and ecological perturbations.

Hemorrhagic fever is a clinical and imprecise definition for several different diseases. Their main common point is to be zoonoses. These diseases are due to several viruses which belong to different families. The Flaviviridae have been known for the longest time. They include the Amaril virus that causes yellow fever and is transported by mosquitoes. Viruses that have come to light more recently belong to three other families: Arenaviridae, Bunyaviridae, and Filoviridae. They are transmitted by rodents (hantaviruses and arenaviruses) or from unknown reservoirs (Ebola Marburg). The primary cause of most outbreaks of hemorrhagic fever viruses is ecological disruption resulting from human activities. The expansion of the world population perturbs ecosystems that were stable a few decades ago and facilitates contacts with animals carrying viruses pathogenic to humans. Another dangerous human activity is the development of hospitals with poor medical hygiene. Lassa, Crimean-Congo or Ebola outbreaks are mainly nosocomial. There are also natural environmental changes: the emergence of Sin Nombre in the U.S. resulted from heavier than usual rain and snow during spring 1993 in the Four Corners. Biological industries also present risks. In 1967, collection of organs from monkeys allowed the discovery in Marburg of a new family of viruses, the Filoviridae. Hemorrhagic fever viruses are cause for worry, and the avenues to reduce their toll are still limited.

[Pathologies associated with HTLV-1 virus in Dakar (1992-1995)]. / Pathologies associées au virus HTLV-1 à Dakar (1992-1995).

A clinical and laboratory study was conducted in Dakar (Senegal) to assess the involvement of HTLV-1 virus (human T lymphotrophic virus type 1) in various diseases. Patients were enrolled at three locations: the Dermatology Department of the Fann University Hospital Center (845 patients) from 1992 to 1995, the Dermatology Department of the Le Dantec University Hospital Center and the Oncology Department of the Principal Hospital (7 patients) in 1994 and 1995. The incidence of involvement of human retroviruses in neurologic complications seemed low (HTLV-1: 2%, HIV: 3%) and only 6 cases of tropical spastic paraparesis associated with specific anti-HTLV-1 antibodies were diagnosed in 3 men and 3 women with a mean age of 51 years. These cases which were identical to those previously described cases in the West Indies and Japan confirms the existence of this disease in Senegal. In addition 3 cases of isolated facial paralysis were observed in HIV positive patients. Combined HIV/HTLV-1 infection was observed in 3 cases and was not associated with special clinical findings. Adult T-cell leukemia/lymphoma (ATL) was detected in 4 patients including leukemia with proliferation of CD4 and CD25 in two cases and lymphoma in one case. In one case of ATL two proviruses were identified in circulating tumor cells. These are the first cases of ATL to be reported in Senegal. Molecular characterization of part of the envelope gene (gp 21) from patients with PST hospitalized in a neurology ward showed that the virus present in Senegal belonged to the universal HTLV-1 A type. This study indicates that two types of diseases are associated with HTLV-1 infection in Senegal. Further epidemiologic studies will be needed to evaluate the incidence of the virus and of the diseases associated with it. Prevention will depend partly on screening blood donors as has now been started at the Blood Transfusion Center of Dakar.

[Serologic screening of certain zoonoses in the abattoir personnel in Djibouti]. / Dépistage sérologique de certaines zoonoses sur le personnel de l'abattoir de Djibouti-ville.

A sero-prevalence survey was carried out on 108 workers of Djibouti slaughter-house in order to search out the carriers of agents of zoonotic diseases. The sera revealed prevalences of 6.5% for brucellosis, 0.9% for chlamydiosis and 42.6% for toxoplasmosis whereas no positive reactions were detected for Rift valley fever, Crimean Congo hemorrhagic fever, hydatidosis, and toxocarosis. These data are compared with results obtained from cattle and small ruminants slaughtered in Djibouti.

Emerging viruses.

Hemorrhagic fever viruses are among the most dangerous biological agents known. New ones are discovered every year, and artificial as well as natural environmental changes are favoring their spread.

Isolation and partial characterisation of a new strain of Ebola virus.

We have isolated a new strain of Ebola virus from a non-fatal human case infected during the autopsy of a wild chimpanzee in the Côte-d'Ivoire. The wild troop to which this animal belonged has been decimated by outbreaks of haemorrhagic syndromes. This is the first time that a human infection has been connected to naturally-infected monkeys in Africa. Data from the long-term survey of this troop of chimpanzees could answer questions about the natural reservoir of the Ebola virus.