[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.

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.

[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.

[The French Committee for the prevention and control of influenza and the 2009 influenza pandemic: Lessons learnt]. / Comité de lutte contre la grippe et la pandémie 2009 : retour d'expérience.

The Committee for the Prevention and Control of Influenza (Comité de lutte contre la Grippe - CLCG) is an advisory committee to the French Health Minister for a medical and scientific collective expertise on the measures to be implemented to control or to reduce the impact of an epidemic or a pandemic of influenza. Appointed by decree, the CLCG consists of ex-officio members; representatives of French Agencies strongly involved by influenza and qualified personalities, representing various fields of expertise. Collective expertise is based on consensus after thorough collective discussion. A notice is drafted in reply to every official question and passed on either to the Chief Medical Officer, or, when the question concerns vaccines, to the Technical Committee of the vaccinations for which the CLCG acted as a working group. The CLCG was extremely active throughout the pandemic. The objective of this article is to describe in a factual way its output throughout this period of sanitary crisis. This article presents and compare chronologically and in a factual way the state of the scientific knowledge about influenza due to the A(H1N1)pdm09 virus and the CLCG notices. Between the alert launched by the WHO the 24th of April and the 31st of December 2009, CLCG met on 40 occasions. Its work dealt in particular with patient care, recommendations on medical treatment (antivirals, seasonal and pandemic vaccines), and on virological diagnosis. Whatever the defects of its expertise delivered in a context of urgency, which was a difficult exercise, the CLCG fulfilled its advisory to the health authorities. However, the pandemic experience showed that this expertise must be improved by insuring the recognition and the visibility of the advisory committee and by defining their exact position in the chain of decision.

Circulation of genotype 4 hepatitis E virus in Europe: first autochthonous hepatitis E infection in France.

BACKGROUND: Human HEV infections reported in Europe without previous travel to endemic regions are linked to exposure to genotype 3 Hepatitis E virus (HEV).Genotype 3 is widely distributed through human cases and zoonotic reservoir. The geographical distribution of genotype 4 is limited to Asian countries. OBJECTIVES: The first human case of autochthonous genotype 4 hepatitis E infection was reported in France. STUDY DESIGN: The HEV infection was described in an immunosuppressed patient, presenting an acute myeloblastic leukemia. Investigation of the case was performed on detection of HEV markers in the patient and in the environment. RESULTS: Hepatitis E infection was diagnosed on the basis of HEV RNA viremia, and detection of anti-HEV IgM. The prognostic of leukemia was favorable and HEV was cleared without relapsing. HEV isolate was classified into genotype 4. CONCLUSIONS: The recent characterization of genotype 4 HEV through swine surveillance in Europe and the description of the first human case in France open interesting questions about the circulation of this genotype: health risks in human population, transmission patterns, and zoonotic reservoir.

Prevalence of antibodies and RNA genome of hepatitis E virus in a cohort of French immunocompromised.

BACKGROUND: Recently, cases of chronic hepatitis E have been identified in immunocompromised patients. OBJECTIVES: To evaluate the prevalence of anti-HEV IgG antibodies and the persistence of HEV-RNA in sera of immunocompromised patients with regular follow-up at Saint-Louis Hospital in Paris, France. STUDY DESIGN: 307 samples collected from 261 HIV-infected patients and 46 kidney transplant (KT)-patients were retrospectively tested for the presence of the following hepatitis E virus (HEV) infection markers: anti-HEV IgM antibodies, anti-HEV IgG antibodies, anti-HEV IgG avidity index, and HEV-RNA. RESULTS: Anti-HEV IgG positive serology was found in 4 HIV-infected patients (1.5%) and 3 KT-patients (6.5%), leading to an overall seroprevalence of 2.3%. HEV-RNA detection was not observed among 55 HIV-patients at higher risk of chronic HEV (<200 CD4 cells/mm(3), elevated alanine aminotransferase (ALT) levels, and/or positive anti-HEV antibodies) and among 44 KT-patients. None of the seven patients had anti-HEV IgM antibodies, thereby excluding any acute infection. The IgG avidity index confirmed past HEV infection among tested patients. CONCLUSIONS: The low seroprevalence observed in the Paris region does not warrant a systematic evaluation of HEV infection in immunocompromised patients. However, HEV infection must be examined as a possibility if unexplained increases in ALT should occur and after more common viral hepatitis infections are excluded.

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.

Acute pancreatitis: a rare complication of acute hepatitis E.

Hepatitis E is an emerging imported disease in Europa but autochthonous cases are described for some years. Extra-hepatic associated manifestations are published. We report a case of acute necrotizing pancreatitis associated with imported acute viral E hepatitis (genotype 1a) in a 26 years old French man travelling and originated from Pakistan. The outcome is favourable spontaneously in two months. This life-threatening hepatitis E related complication is unknown in Europa where genotype 3 virus strains prevail. The clinical presentation is stereotyped with the onset of pancreatitis in the second or third weeks of hepatitis evolution in an Indian male in his second or third decade infected with genotype 1 strain. No pancreatitis-related death is reported in the 13 previous reported cases.

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.

Sustained virologic response with ribavirin in chronic hepatitis E virus infection in heart transplantation.

Hepatitis E virus (HEV) is an emerging problem amongst transplant recipients. We report a patient with chronic HEV hepatitis after a heart transplant. The patient received a 3-month course of oral ribavirin (17 mg/kg/day). HEV RNA became undetectable in the serum after 1 month of treatment and remained undetectable in serum and stool samples until the last follow-up, 2 months after completion of ribavirin therapy. The values of liver function indicators returned to normal reference ranges. The main ribavirin-induced side effect was a significant but well-tolerated anemia. We confirmed that ribavirin may induce a sustained virologic response (4 months after ribavirin cessation) in heart transplant patients with chronic HEV infection. Liver cytolysis is rather common in patients after heart transplantation. Rapid evolution to liver fibrosis lesions and available anti-viral therapy highlight the need to look for HEV infection in heart transplant recipients with unexplained hepatitis.

Incidence, etiology, and determinants associated with acute diarrhea among French forces deployed to Chad.

BACKGROUND: This study assesses, for the first time, the incidence, etiology, and determinants associated with traveler's diarrhea (TD) among French forces deployed to N'Djamena, Chad. METHODS: A prospective study was conducted based on physician consultation for diarrhea during a 5-month French forces mandate. Diarrhea was defined as ≥3 loose stools in a 24-hour period or ≥2 loose stools within the last 8 hours. For each diarrheic episode, an anonymous physician-administered questionnaire was completed and a stool sample collected. Samples were tested for parasites, bacteria, and enteric viruses. Global incidence rate was calculated using the mean number of soldiers based in N'Djamena (n = 1,024) over the 5-month period, as denominator. Incidence rates were also estimated for each of the eleven 2-week periods of stay. A case-crossover analysis estimated determinants associated with diarrhea. RESULTS: A total of 240 cases of diarrhea were notified by military physicians, resulting in a global incidence rate of 49 cases per 1,000 person-months (PM). The cumulative individual risk of developing diarrhea during the study period was 0.23. The incidence per 2-week stay began at 8.8/1,000 PM, rose to 54.4/1,000 PM after 1 month, and decreased after 2 months. Of the 240 cases reported, stool samples were obtained for 196 cases. Pathogens were identified in 40% of samples; enteric viruses were predominant (28.1%). Three determinants were associated with diarrhea by multivariate analysis: diarrhea in the close circle [OR: 3.8 (2.0-7.0)]; always eating at the military mess [OR: 0.2 (0.1-0.5)]; or staying in a temporary encampment [OR: 0.3 (0.1-0.8)]. CONCLUSIONS: This study found a high frequency of enteric viruses and a high risk of person-to-person transmission associated with diarrhea. Eating at the military mess or staying in a temporary encampment conferred a protective effect. In addition to food-borne disease prevention, stringent hygiene measures are required to break transmission of diarrhea during military deployments.

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.

Hepatitis E virus in HIV-infected patients.

OBJECTIVES: Many cases of acute autochthonous hepatitic E virus (HEV) hepatitis have been reported in France, mainly from the south. Chronic HEV infection has recently been described in immunosuppressed patients. Although a potential risk of chronicity exists in HIV-infected patients, no survey has been conducted in this population. The aim of this study was to assess the sero-virological prevalence of HEV in French HIV-infected patients. METHODS: Two hundred and forty-five HIV-infected patients followed at two Infectious Diseases Departments (one in the south, one in the north) were included from January to March 2009. Sera were collected from all patients and tested using anti-HEV IgG and IgM kits. HEV RNA was systematically amplified in the ORF2 region with an in-house method. The IgG avidity index of all IgG-positive samples was determined. RESULTS: Three of the 133 southern patients showed both anti-HEV IgG and IgM positivities, along with cytolysis and biological cholestasis; HEV RNA was amplified in two of these cases, whereas a low IgG avidity index was observed in all three samples. Twelve of the 130 remaining southern patients (9%) showed anti-HEV IgG positivity. The serological prevalence in the 112 northern patients was 3%, which was significantly lower than in the southern patients (P=0.04). No case of acute hepatitis was reported in the north, whereas the prevalence of patients with biochemical liver abnormalities was similar in both areas (P=0.22). CONCLUSIONS: In France, HIV-infected patients are at risk of HEV infection with a serological north-to-south gradient. No case of chronic HEV infection was detected in this study.

[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.

Use of hepatitis E IgG avidity for diagnosis of hepatitis E infection.

The diagnosis of acute hepatitis E infection is based on the detection of HEV RNA or specific IgM in immunocompetent patients. Viraemia and excretion of HEV RNA in faeces are not observed in all patients and commercial kits vary in their performance for anti-HEV IgM detection. Additional diagnostic tests must therefore be considered. The value of anti-HEV IgG avidity index for differentiating between acute infection and previous exposure to HEV in countries of low endemicity was investigated. 132 specimens were included, with 39 serum samples from patients with known HEV infection, studied retrospectively. IgG avidity index was high (>60%) in patients with previous infection (n=16) or polyclonal activation (n=3) but was low (<40%) in patients with acute infection (n=20). Then, 93 serum samples from patients, checking for acute hepatitis (detection of anti-HEV IgM but not of HEV RNA) were investigated. IgG avidity index was <40% in 77 of these patients, consistent with acute infection. It exceeded 60% in 15 patients, providing evidence of contact with HEV up to six months previously. One patient had an uninterpretable biological profile, with an IgG avidity index between 40% and 60%. IgG mature slowly during HEV infection, over a period of six months. IgG avidity index can therefore be used to exclude primary infection. This method should improve the diagnosis of acute hepatitis E.