[Autochthonous hepatitis E: an emerging and still unrecognized disease]. / Hépatite E autochtone: une maladie emergente encore méconnue.

In developed countries, HEV infection was still recently considered as rare, and as an imported disease from endemic areas by travellers. Hepatitis E virus is now mainly recognized as an autochthonous disease in these countries. Although the sources and the routes of contamination remain uncertain, several cases of foodborne (zoonotic transmission) and blood borne transmission have been recently reported. HEV infection may evolve towards a chronic hepatitis in immunocompromised patients (mostly in solid organ transplant recipients and patients with HIV) which can evolve to cirrhosis. The mortality rates in industrialized countries seem to be higher than in endemic areas. By contrast, whereas mortality rate reaches 20% during pregnancy in developing countries, no death in pregnant woman secondary to an autochthonous case has been reported so far in developed countries.

Close similarity between sequences of hepatitis E virus recovered from humans and swine, France, 2008-2009.

Frequent zoonotic transmission of hepatitis E virus (HEV) has been suspected, but data supporting the animal origin of autochthonous cases are still sparse. We assessed the genetic identity of HEV strains found in humans and swine during an 18-month period in France. HEV sequences identified in patients with autochthonous hepatitis E infection (n = 106) were compared with sequences amplified from swine livers collected in slaughterhouses (n = 43). Phylogenetic analysis showed the same proportions of subtypes 3f (73.8%), 3c (13.4%), and 3e (4.7%) in human and swine populations. Furthermore, similarity of >99% was found between HEV sequences of human and swine origins. These results indicate that consumption of some pork products, such as raw liver, is a major source of exposure for autochthonous HEV infection.

Hepatitis E virus infection in HIV-infected patients with elevated serum transaminases levels.

Increases in aminotransferases levels are frequently encountered in HIV-positive patients and often remain unexplained. The role in this setting and natural history of hepatitis E in HIV-infected patients are unknown. The aim of the study was to assess HEV infection in HIV-infected patients attending a Parisian hospital, with a current or previous cryptogenic hepatitis.191 plasma samples collected from 108 HIV-infected patients with elevated aminotransferases levels were retrospectively tested for the presence of hepatitis E virus (HEV) infection markers: anti-HEV IgM antibodies, anti-HEV IgG antibodies, anti-HEV IgG avidity index and plasma HEV RNA.One acute infection, documented by positive tests for anti-HEV IgM antibody, low anti-HEV IgG avidity index and plasma HEV RNA (genotype 3e), and three past infections were diagnosed, without any observed case of persistent infection. The acute hepatitis was benign and resolved spontaneously within two weeks. This infection was probably contracted locally. Acute HEV hepatitis can occur in HIV-infected patients but rarely explains cryptogenic hepatitis, at least in an urban HIV population, regardless geographic origin and CD4 counts.

Brief communication: case reports of ribavirin treatment for chronic hepatitis E.

BACKGROUND: There is currently no accepted treatment of chronic hepatitis E virus (HEV) infection. OBJECTIVE: To report 2 patients in whom ribavirin therapy seemed to alter the natural history of chronic HEV infection. DESIGN: Case reports. SETTING: Hepatology unit of a tertiary care center in France. PATIENTS: A kidney and pancreas transplant recipient and a patient with idiopathic CD4(+) T lymphocytopenia, both with biopsy-proven chronic HEV infection. INTERVENTION: Patients received oral ribavirin, 12 mg/kg of body weight daily for 12 weeks. MEASUREMENTS: Liver function tests, detection of HEV RNA (viremia and stool shedding) by reverse transcriptase polymerase chain reaction, and anti-HEV IgM and IgG antibodies. RESULTS: Both patients had normalized liver function test results after 2 weeks of treatment and cleared HEV after 4 weeks of treatment. Hepatitis E virus RNA remained undetectable in the serum and stools throughout follow-up (3 months and 2 months for the first and second patient, respectively). Side effects were considered mild. LIMITATION: Given the relatively short follow-up, the achievement of HEV eradication could not be claimed. CONCLUSION: Ribavirin is a potentially effective treatment of HEV infection and should be evaluated in patients with chronic HEV infection. PRIMARY FUNDING SOURCE: None.

[Disseminated Trichosporon asahii infection]. / Infection invasive à Trichosporon asahii.

The present report describes a case of disseminated Trichosporon asahii infection. Trichosporon species has emerged as opportunistic infectious yeast in immunocompromised patients and is resistant to echinocandins. These antifungal drugs are not recommended for trichosporonosis treatment and yeast species identification be attempted for all clinical isolates, particularly with respect to the choice of antifungal therapy for specific Trichosporon species.

[Survey of diarrhoea survey in Kosovo Mitrovica. August 2001]. / Etude sur les diarrhées à Mitrovicè (Kosovo) en août 2001.

The upsurge of diarrhoea observed in children in Kosovo Mitrovica in the spring of 2001 led to a survey, jointly organized by the city health department, the GISPE association and the medical laboratory at the Val de Grâce Hospital (France). The available retrospective data showed an increase in cases of diarrhoea in which Giardia duodenalis was isolated. During the third week of August 2001, all children with diarrhoea consulting in the hospital south of city (n = 45) had a complete stool analysis. The analyses showed the presence of Giardia cysts and trophozoites in 40% of the cases, and no cases with helminthes or cryptosporidia. Moreover 3 strains of S. sonnei, a microorganism never previously identified, and different pathovars of E. coli in 11 patients were isolated. This "epidemic" appeared to be linked to the poor hygiene conditions that still prevailed 2 years after the events but not directly to the water supply, which was rehabilitated at the end of 1999. It is also necessary to strengthen the capacity of the public laboratories and health-care facilities of the province.

[Policies vaccination against the Human papillomavirus infections in France and worldwide]. / Politique de vaccination contre les infections à papillomavirus humains en France et dans le monde.

Policies vaccination against the human papillomavirus infections in France and worldwide. Since 2007, french guidelines have recommended HPV vaccination for female aged to 14-23 years old then 11 to 19 years old in 2012, and expanded to men who have sex with men aged up to 26 years in 2016. The impact of HPV vaccine programm regarding reduction of high grade cervical precancerous lesions in women was limited by a very low vaccine coverage in France. Safety concerns of this vaccination, lack of practical information for healthcare and citizens could potentially raise vaccine hesitancy.

Politiques de vaccination contre les infections à papillomavirus humains en France et dans le monde. Depuis la disponibilité des vaccins Gardasil et Cervarix en 2007, puis Gardasil 9 en 2016, la prévention des maladies liées aux infections par les papillomavirus à haut risque se fait par la vaccination des jeunes filles de 11 à 19 ans et des hommes ayant des relations sexuelles avec les hommes jusqu'à l'âge de 26 ans. Cette politique vaccinale s'est heurtée à une forte réticence, avec pour conséquence une couverture vaccinale très insuffisante par rapport à l'objectif fixé à 60 %. Les pays ayant une couverture vaccinale élevée ont mis en évidence un impact direct de cette vaccination sur l'incidence des lésions précancéreuses du col de l'utérus. L'inquiétude vis-à-vis de la tolérance des vaccins, le défaut d'information pour les médecins de 1re ligne et le public ont participé à l'hésitation vaccinale.

Outbreak of hepatitis E virus infection in Darfur, Sudan: effectiveness of real-time reverse transcription-PCR analysis of dried blood spots.

Biological samples collected in refugee camps during an outbreak of hepatitis E were used to compare the accuracy of hepatitis E virus RNA amplification by real-time reverse transcription-PCR (RT-PCR) for sera and dried blood spots (concordance of 90.6%). Biological profiles (RT-PCR and serology) of asymptomatic individuals were also analyzed.

Seroprevalence and risk factors of hepatitis E among women of childbearing age in the Xieng Khouang province (Lao People's Democratic Republic), a cross-sectional survey.

BACKGROUND: Endemic hepatitis E in Southeast Asia increases the risk of death in pregnant women. In Lao People's Democratic Republic, infection with hepatitis E virus (HEV) is widespread in pig farms. No human data are available yet. This study determined the prevalence and risk factors for HEV infection among women of reproductive age living in urban and rural areas. METHODS: A cross-sectional study was conducted in Xieng Khouang province, selected for its high prevalence of HEV in pig farms, after a two-stage random sampling. Blood eluates of filter paper samples were tested by enzyme-linked immunosorbent assay for anti-HEV immunoglobulin G (IgG). Risk factors were investigated by bivariate and multivariate analyses. RESULTS: Of 226 women (112 rural and 114 urban), anti-HEV IgG was detected in 66 (29.2%), with more in rural than in urban areas (38.4% vs 20.2%; p=0.005). Age (25-29 y) and farming profession were associated with HEV positivity. Living in an urban area, a supply of clean drinking water and raw duck blood consumption were protective. CONCLUSIONS: Risks of HEV infection are more related to lack of drinking water resources than to promiscuity with pigs. Women of childbearing age could be targeted by future vaccination programs. Consumption of drinking water should be recommended during pregnancy.

Detection and characterization of Human caliciviruses associated with sporadic acute diarrhea in adults in Djibouti (horn of Africa).

Recent advances in molecular diagnostics have allowed us to recognize Human caliciviruses (HuCVs) as important agents of acute diarrhea in industrialized countries. Their prevalence and genetic diversity in developing countries remains unknown. We report on the characterization of HuCVs among adults presenting acute diarrheas in Djibouti; 108 stool samples collected were screened by EIA, RTPCR, or cell cultures for the group A Rotaviruses, Adenoviruses, Astroviruses, and HuCVs, which were further characterized by genotyping. Among stool samples screened for HuCVs, 25.3% were positive. The other enteric viruses were less prevalent. The 11 HuCV strains sequenced revealed a large diversity (3 sapoviruses and 8 noroviruses). GII strains noroviruses were predominant, five were newly described genotypes, and two were recombinant with a pol gene related to GGIIb strains with the particularity to associate a unique pol gene to different capsid genes. These results could help to the knowledge of HuCV infections in Tropical Africa.

Acute hepatitis E with severe jaundice: report of three cases.

Hepatitis E virus (HEV) is the main cause of enterically transmitted non-A hepatitis worldwide. Infection is endemic in developing countries. Disease course is benign, and severe jaundice is rarely reported. Three patients presented to our department with symptomatic acute hepatitis. Two of them had recently travelled to endemic areas. Jaundice was very marked in all patients. HEV infection was documented by HEV antibodies and by HEV-RNA detection in serum and stools. In the autochthonous case, immunoglobulin-M was absent, and diagnosis was established on HEV-RNA amplification by real-time reverse transcriptase-PCR. Comprehensive investigation for concomitant causes of liver disease was negative in all patients. Histological features showed marked cholestasis with multiple bile plugs in dilated canaliculi. In conclusion, acute hepatitis E may be autochthonous in developed countries and patients may present with severe jaundice. HEV-RNA detection by real-time reverse transcriptase-PCR is a very efficacious diagnostic tool in anti-HEV immunoglobulin-M-negative cases.

[Autochthonous hepatitis E in France and consumption of raw pig meat]. / Hépatite virale E autochtone en France et consommation de viande de porc séchée.

Viral hepatitis E is an endemic infection in developing countries. Emerging cases of autochthonous hepatitis E have been observed in developed countries, especially in France. Transmission route of those cases remains unknown and contamination may occur from an animal reservoir. We report two new cases of hepatitis E simultaneously diagnosed in a couple after a trip in southern France. Diagnosis was based on detection of anti-HEV IgM and HEV RNA in sera of the two patients. Epidemiologic investigation revealed that the two patients had eaten undercooked pig meat four weeks before the onset of the jaundice. This report suggests that consumption of undercooked pork meat may be responsible for the contamination by hepatitis E virus in France as it was described in Japan.

High mortality associated with an outbreak of hepatitis E among displaced persons in Darfur, Sudan.

BACKGROUND: Hepatitis E virus (HEV) causes acute onset of jaundice and a high case-fatality ratio in pregnant women. We provide a clinical description of hospitalized case patients and assess the specific impact on pregnant women during a large epidemic of HEV infection in a displaced population in Mornay camp (78,800 inhabitants), western Darfur, Sudan. METHODS: We reviewed hospital records. A sample of 20 clinical cases underwent laboratory confirmation. These patients were tested for immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody to HEV (serum) and for amplification of the HEV genome (serum and stool). We performed a cross-sectional survey in the community to determine the attack rate and case-fatality ratio in pregnant women. RESULTS: Over 6 months, 253 HEV cases were recorded at the hospital, of which 61 (24.1%) were in pregnant women. A total of 72 cases (39.1% of those for whom clinical records were available) had a diagnosis of hepatic encephalopathy. Of the 45 who died (case-fatality ratio, 17.8%), 19 were pregnant women (specific case-fatality ratio, 31.1%). Acute hepatitis E was confirmed in 95% (19/20) of cases sampled; 18 case-patients were positive for IgG (optical density ratio > or =3), for IgM (optical density ratio >2 ), or for both, whereas 1 was negative for IgG and IgM but positive for HEV RNA in serum. The survey identified 220 jaundiced women among the 1133 pregnant women recorded over 3 months (attack rate, 19.4%). A total of 18 deaths were recorded among these jaundiced pregnant women (specific case-fatality ratio, 8.2%). CONCLUSIONS: This large epidemic of HEV infection illustrates the dramatic impact of this disease on pregnant women. Timely interventions and a vaccine are urgently needed to prevent mortality in this special group.

A large outbreak of hepatitis E among a displaced population in Darfur, Sudan, 2004: the role of water treatment methods.

BACKGROUND: The conflict in Darfur, Sudan, was responsible for the displacement of 1.8 million civilians. We investigated a large outbreak of hepatitis E virus (HEV) infection in Mornay camp (78,800 inhabitants) in western Darfur. METHODS: To describe the outbreak, we used clinical and demographic information from cases recorded at the camp between 26 July and 31 December 2004. We conducted a case-cohort study and a retrospective cohort study to identify risk factors for clinical and asymptomatic hepatitis E, respectively. We collected stool and serum samples from animals and performed a bacteriological analysis of water samples. Human samples were tested for immunoglobulin G and immunoglobulin M antibody to HEV (for serum samples) and for amplification of the HEV genome (for serum and stool samples). RESULTS: In 6 months, 2621 hepatitis E cases were recorded (attack rate, 3.3%), with a case-fatality rate of 1.7% (45 deaths, 19 of which involved were pregnant women). Risk factors for clinical HEV infection included age of 15-45 years (odds ratio, 2.13; 95% confidence interval, 1.02-4.46) and drinking chlorinated surface water (odds ratio, 2.49; 95% confidence interval, 1.22-5.08). Both factors were also suggestive of increased risk for asymptomatic HEV infection, although this was not found to be statistically significant. HEV RNA was positively identified in serum samples obtained from 2 donkeys. No bacteria were identified from any sample of chlorinated water tested. CONCLUSIONS: Current recommendations to ensure a safe water supply may have been insufficient to inactivate HEV and control this epidemic. This research highlights the need to evaluate current water treatment methods and to identify alternative solutions adapted to complex emergencies.

[Autochthonous hepatitis E in France]. / Hépatite E autochtone en France.

Hepatitis E must no longer be considered simply as an exotic disease occasionally imported from developing countries. Autochthonous hepatitis E exists in France. In spite of certain difficulties and limits, biological markers of hepatitis E have to be included in algorithms for etiological diagnosis of acute hepatitis, even if the patient has not recently traveled abroad. Based on a recombinant protein of the viral capsid, more sensitive serological assays should soon be available. The potential severity of hepatitis E, especially during pregnancy, calls for a national surveillance program, including evaluation of the animal reservoir and the risk associated with drinking water and food.

Short communication. Antiretroviral drug resistance among drug-naive HIV-1-infected individuals in Djibouti (Horn of Africa).

OBJECTIVE: To survey the frequency of genotypic antiretroviral resistance in drug-naive HIV-1-infected Djiboutians. METHODS: A national study was conducted in the general population of Djibouti in March 2002 to determine HIV-1 seroprevalence. Blood samples were collected anonymously and plasma samples scoring positive for HIV-1 antibodies were tested for viral load. Genotypic studies were performed with viral RNA from plasma using the consensus technique of the Agence Nationale de Recherche sur le SIDA (www.hivfrenchresistance.org). Mutations were identified using the International AIDS Society-USA resistance panel and resistant virus was defined according to the ANRS algorithm. RESULTS: A panel of 2423 individuals representing the general population of Djibouti was included. Antibodies were detected in 53 of 2423 samples tested. The HIV-1 seroprevalence in the general population was 2.2%. Genotype C was the most prevalent, and the other isolates were CRF_02 AG, or subtype A or D. Forty-seven of the 53 samples were tested for genotypic resistance, and mutations concerning all three classes of antiretrovirals were found. The most frequent were secondary mutations associated with protease inhibitors (PIs): M36I, R41K and K20I/R. A few strains displayed primary mutations (the non-nucleoside reverse transcriptase inhibitor [NNRTI]-associated mutations K101E, K103T, L100I and G190V; the PI-associated mutation N88D; and the NRTI-associated mutation K65R). The presence of these mutations may be due to the transmission of strains from treated patients. CONCLUSION: Substantial polymorphism and a few primary mutations are found in HIV-1 non-B subtype isolates from Djiboutian antiretroviral-drug-naive individuals. This needs to be taken into account to adapt antiretroviral regimens and prophylactic schedules locally.