Declining hepatitis E virus antibody prevalence in Phnom Penh, Cambodia during 1996-2017.

Hepatitis E virus (HEV) infection is endemic in Cambodia. However, little relevant data were available and there is no clue if HEV is an emerging or decreasing pathogen in that setting. The aim of our study was to describe temporal trends of anti-HEV IgG and IgM prevalences during the last two decades (1996-2017) in the context of population growth and urbanisation in Cambodia. A total of 2004 human plasma samples collected between 1996 and 2017 were tested for anti-HEV IgG and IgM using the commercial Wantai anti-HEV assays. Overall, the prevalences of anti-HEV IgG and IgM were 41.1% and 2.7%, respectively. Analysis by calendar period showed a decreasing trend of anti-HEV IgG prevalence over the last 21 years. After age- and gender-standardisation, the anti-HEV IgG prevalence rates decreased from 61.3% during the 1996-2000 period to 32.3% during the 2016-2017 period, but no trends were observed for anti-HEV IgM rates, which fluctuated around the overall one. In conclusion, our results suggest that HEV is not an emerging pathogen, but rather seems to circulate less in Cambodia, in particular, in Phnom Penh, since the prevalence of anti-HEV IgG has been significantly decreased during the past two decades.

Analytical and field evaluation of the Biocentric Generic HCV assay on open polyvalent PCR platforms in France and Cambodia.

BACKGROUND: Implementation of affordable methods for HCV viremia is a key priority for identifying individuals who need treatment among persons screened positive for HCV antibodies. Different HCV PCR assays for use on open polyvalent PCR platforms are currently commercially available but studies evaluating the performances of these nucleic acid tests are needed. OBJECTIVES: In the present study, we evaluated the analytical and clinical performances of a recently developed HCV RNA PCR assay for detection and quantification of HCV viremia. STUDY DESIGN: In this study the Biocentric Generic HCV PCR was compared to the Roche Cobas AmpliPrep/Cobas TaqMan HCV RNA assay. Analytical and clinical performances was evaluated on reference materials and HCV plasma samples collected in 141 patients attending at the Montpellier University Hospital in France. Field evaluation was performed on samples collected in 185 patients attending at Medical Laboratory, Institut Pasteur in Cambodia. RESULTS: The lower limit of detection ranged from 50 HCV RNA IU/ml to 300 HCV RNA IU/ml using four different Diasorin and Qiagen automated or manual extraction methods. The specificity (CI) and sensitivity of the assay were 100% (92.5-100), and 98.7% (92.3-99.9), respectively, in France, and 100% (95.5-100), and 100% (94.4-100%), respectively, in Cambodia. Bland-Altman analysis shown good agreement between the two assays including for genotypes 6 HCV, which represent the majority of HCV isolates in Cambodia. CONCLUSIONS: The Biocentric Generic HCV assay has shown overall satisfactory analytical performances and a close agreement to the Cobas HCV assay on clinical specimens collected in France and Cambodia. There is an urgent need to further evaluate commercial assays dedicated to HCV detection and quantification using open polyvalent PCR platforms in different settings.

Hepatitis B, C, and E infection among HIV-infected patients in Franceville, Gabon: retrospective cross-sectional study.

Access to antiretrovirals has increased the life expectancy of patients living with HIV. However, HIV-viral hepatitis coinfections in countries endemic for these infections make management more difficult. To determine the extent of these coinfections in Gabon, we investigated markers of hepatitis B, C, and E viruses in 762 adults infected with HIV-1 by ELISA. We used real-time PCR to quantify plasma HBV DNA (HBV VL) and amplified HCV and HEV RNA by nested RT-PCR and PCR.The seroprevalence of chronic hepatitis B infection was 9.3 %. Among patients with isolated HBcAc profiles, the prevalence of occult hepatitis B infection was 26.7 %, for a real prevalence (detectable CV-HBV) of 17.3 % of the total population. HCV seroprevalence was 8.8 %. Of the 67 HIV-positive patients, 76.1 % had replicative profiles (detectable HCV RNA), that is, 6.7 % of the total population. For hepatitis E, seroprevalence was 3.5 %. No case of chronic HEV infection was found. In conclusion, this study highlights a high rate of HIV-Hepatitis B, C and E coinfections in Gabon. In addition, we show the interest of looking for chronic infections (replicative profiles) in HIV-infected patients in Gabon. The establishment of technical platforms for this type of research, accessible to middle-income countries, is necessary.

24-Month adherence, tolerance and efficacy of once-a-day antiretroviral therapy with didanosine, lamivudine, and efavirenz in African HIV-1 infected children: ANRS 12103/12167.

BACKGROUND: There is no data on long-term benefit of once-a-day antiretroviral therapy (ART) with combination of DDI, 3TC and EFV to allow its use in future therapeutic strategies. OBJECTIVES: To assess 24-month immuno-virological, adherence, tolerance, and effectiveness of a once-a-day ART with DDI, 3TC and EFV. METHODS: A phase 2 open trial including 51 children aged from 30 months to 15 years, monitored a once-a-day regimen for 24 months from 2006 to 2008 in the Departement de Pediatrie du CHUSS, at Bobo-Dioulasso in Burkina Faso. We tested immunological and virological response, adherence, tolerance and resistance of the treatment. RESULTS: Children with CD4 >25% at 24 months were 67.4% (33/49) CI 95% [54%, 80%]. The proportion of children with viral plasma RNA <300 cp / ml at 24 months of treatment was 81.6 % (40/49) CI [68.0% 91.2%]. Good adherence was obtained with more than 88% adherence > 95% over the 24 months. Drugs were well tolerated. CONCLUSIONS: Given the limited number of antiretroviral drugs available in Africa and the inadequacy of laboratory monitoring in support program, once-a-day treatment and especially the DDI-based combination strategies could be an attractive operational option.

Respiratory manifestations in HIV-infected children pre- and post-HAART in Abidjan, the Ivory Coast.

Among children infected with human immunodeficiency virus (HIV), respiratory diseases are a frequent cause of morbidity and mortality. This review describes respiratory manifestations of paediatric HIV infection before and after the beginning of HAART in Abidjan, Ivory Coast. In an observational cohort, HIV infected children had quarterly clinical visits and a day-clinic available all week for ill children. CD4 and viral load were measured at baseline and every 6 months thereafter. All children with a CD4 percentage below 25% were prescribed daily cotrimoxazole prophylaxis. Ninety-eight children (of a total of 282) were recruited before HAART and treated during the follow-up, there were 56 boys and 42 girls, with a mean age of 6.2 years at inclusion. The mean percentage of CD4 before HAART was 8.7%. Twelve children had a history of pulmonary tuberculosis and five were on antituberculosis treatment at inclusion. Fifty-one per cent presented with abnormalities on chest X-ray at inclusion. Before initiation of HAART, respiratory manifestations represented 32.4% of morbidity events and the incidence for 100 child/months was 9.29 for URTI, 15.2 for bronchitis, 6.07 for LRTI, 0.71 for tuberculosis and 0.36 for Pneumocystis carinii. After the initiation of HAART, respiratory manifestations represented 40.9% of all morbidity events and the incidence for 100 child/months was 5.35 for URTI, 9.48 for bronchitis, 2.17 for LRTI and 0.16 for tuberculosis. During HAART treatment, the incidence of respiratory infections decreased dramatically compared to before the antiretroviral treatment. However, respiratory events still represented 40% of all events occurring following the start of HAART therapy.

Epidemiologic study of the association between human T-cell lymphotropic virus type 1 and Strongyloides stercoralis infection in female blood donors (Guadeloupe, French West Indies).

This case control study was conducted among female blood donors in Guadeloupe. A total of 85 HTLV-1 positive subjects were matched by age (+/- 5 years) in a 1:3 ratio to 255 HTLV-1 negative controls. The mean age was 48.5 and 48.9 years respectively. Ethnic, environmental and socio-economic risk factors were studied. Four risk factors were found independently associated with HTLV-1 seropositivity: Strongyloides stercoralis antibodies (OR = 3.6, CI 1.8, 7.3), low socio-economic status (OR = 2.0 CI 1.0, 4.0), low educational level (OR = 2.0 CI 1.0, 4.0) and agricultural activity (OR = 2.8 CI 1.4, 5.6). This logistic regression analysis demonstrates the reality of the association between HTLV-1 carriers and Strongyloides stercoralis, and its association with socio-economic and environmental risk factors.

Epidemiologic study of the association between human T-cell lymphotropic virus type 1 and Strongyloides stercoralis infection in female blood donors (Guadeloupe, French West Indies)

This case control study was conducted among female blood donors in Guadeloupe. A total of 85 HTLV-1 positive subjects were matched by age (+/- 5 years) in a 1:3 ratio to 255 HTLV-1 negative controls. The mean age was 48.5 and 48.9 years respectively. Ethnic, environmental and socio-economic risk factors were studied. Four risk factors were found independently associated with HTLV-1 seropositivity: Strongyloides stercoralis antibodies (OR = 3.6, CI 1.8, 7.3), low socio-economic status (OR = 2.0 CI 1.0, 4.0), low educational level (OR = 2.0 CI 1.0, 4.0) and agricultural activity (OR = 2.8 CI 1.4, 5.6). This logistic regression analysis demonstrates the reality of the association between HTLV-1 carriers and Strongyloides stercoralis, and its association with socio-economic and environmental risk factors

Field evaluation of an improved assay using a heat-dissociated p24 antigen for adults mainly infected with HIV-1 CRF02_AG strains in Côte d'Ivoire, West Africa.

The aim of this study was to evaluate the heat-dissociated p24 antigen (HD p24 Ag) assay as an alternative low-cost tool for diagnosis of HIV-1 infection and quantitation of HIV-1 RNA levels in African adults mainly infected with HIV-1 CRF02_AG strains. One hundred seventeen plasma specimens were obtained from HIV-1-seropositive subjects enrolled in the ANRS 1220 PRIMO-CI cohort (Abidjan, Côte d'Ivoire, West Africa). Results of the HD p24 Ag assay were comparable with those of HIV-1 RNA levels quantified in the same antibody-positive plasma samples by the Amplicor HIV-1 Monitor assay (1.5 version; Roche Diagnostics, Indianapolis, IN): sensitivity, 95.7% versus 96.6%, respectively; specificity (evaluated with samples from 75 seronegative subjects), 94.7% versus 100%, respectively. HD p24 Ag and HIV-1 RNA assays were weakly correlated (Spearman coefficient correlation, r = 0.33; P < 0.001) except for HIV-1 RNA levels of >/=5 log10 copies/mL (r = 0.62; P < 0.001). Quantitation of HD p24 antigenemia in 76 plasma specimens from 14 patients treated with highly active antiretroviral therapy demonstrated weaker changes during treatment than those observed with the HIV-1 RNA assay. Follow-up of infected patients using both markers showed different results. The reliability of the HD p24 Ag assay is questionable for clinical and biologic management as a surrogate tool for measurement of HIV-1 RNA levels in Africa.

[Cards of information and informed consent. Proposal of 14 information cards for plastic and aesthetic surgery]. / Fiches d'information et consentement éclairé. Proposition de 14 fiches d'information concernant la chirurgie plastique et esthétique.

Obligation to deliver full information and obtaining enlightened assent are now, for the whole French practitioner, a necessary preliminary to each operation. Henceforth, in case of suit, the practitioner must prove the reality and the quality of preoperatoire information. The National Medical French Council (CNOM) called scientific societies attention to propose to their members some index standard cards, corresponding to mail medical and surgical records. The National Agency for Accreditation and Evaluation in Health (Anaes) defined the main characteristics of these documents. The authors propose fourteen information cards corresponding to the most currently operations of plastic and aesthetic surgery. They will being clear and simple, wtih a large agreement, strictly informative and yearly up to date. They have the label and therefore the scientific guarantee of French Society of Plastic Reconstructive and Aesthetic Surgery.

A case-control study of risk factors associated with human T-cell lymphotrophic virus type-I seropositivity in blood donors from Guadeloupe, French West Indies.

BACKGROUND AND OBJECTIVES: An age- and gender-specific distribution characterizes human T-cell lymphotrophic virus type-I (HTLV-I) seropositivity in Guadeloupe (French West Indies). Further epidemiological studies are required to identify other possible risk factors associated with this retroviral infection. MATERIALS AND METHODS: A nested case-control study was conducted between 1997 and 1999 among blood donors. A total of 102 HTLV-I-positive subjects were matched (at a ratio of 1 : 3) by gender, age (+/-5 years) and donor status (new or regular) to 306 HTLV-I-negative controls. Information was obtained through a questionnaire assessing both environmental and behavioural variables. RESULTS: Factors independently associated with HTLV-I infection included a low level of education [odds ratio (OR) 6.61, confidence interval (CI) 2.89-15.15], black ethnicity (OR 3.28, CI 1.01-10.65), two or more sex partners in the previous 3 years (OR 2.43, CI 1.16-5.10), early age at first sexual intercourse (0.84 risk reduction per additional year, CI 0.76-0.93), a history of sexually transmitted diseases (OR 2.29, CI 1.0-5.34) and positive Chlamydia serology (OR 1.95, CI 1.03-3.68). CONCLUSION: These data provide a wide spectrum of features associated with HTLV-I seropositivity, especially sexual risk factors. It strongly suggests that heterosexual intercourse is an important route of HTLV-I transmission in Guadeloupe, even among low-risk populations such as blood donors.

Early diagnosis of paediatric HIV-1 infection among African breast-fed children using a quantitative plasma HIV RNA assay.

OBJECTIVE: To evaluate the performance of a quantitative plasma HIV-1 RNA assay for HIV infection diagnosis among African breast-fed children. METHODS: Serial plasma specimens collected in the first week, at day 45-90, 6 months and 9-12 months of age from HIV-exposed children born to HIV-1-infected women enrolled in the DITRAME ANRS 049a perinatal intervention trial (Abidjan, Côte d'Ivoire) were tested for HIV-1 plasma RNA using a branched DNA (bDNA) assay. Sensitivity and specificity of this RNA test were assessed in comparison with a qualitative DNA polymerase chain reaction (PCR) performed on the same blood samples and allowing a reliable detection of the predominant subtype A. RESULTS: Among 91 samples from 53 infected children which tested positive by DNA PCR, the sensitivity of the bDNA test was 100% [95% confidence interval (CI), 96.0-100.0] at < or = 8 days (n = 19), 6-12 weeks (n = 43), 6 months (n = 26), and 9-12 months (n = 3). The median plasma HIV-1 RNA viral load ranged from 242 000 copies/ml at < or = 8 days to more than 500 000 copies/ml at day 45-90 and at 6 months. Of 106 specimens from 106 uninfected children who were DNA PCR- negative at month 3 or 6 of age, HIV-1 RNA was undetectable in 103, yielding an overall specificity for the bDNA test of 97.2% (95% CI, 92.0-99.4). The viral load in the three remaining samples with false-positive results was low (410, 937 and 3752 copies/ml, respectively). CONCLUSIONS: The quantitative bDNA assay appears a suitable tool for early, reliable and easy diagnosis of paediatric HIV-1 infection among a population of African breast-fed children.

Seroprevalence of human herpes virus 8 antibody in populations at high or low risk of transfusion, graft, or sexual transmission of viruses.

BACKGROUND: The routes of transmission of human herpes virus 8 (HHV-8) remain unclear. In particular, HHV-8 transmission by blood components and organ transplantation is still debated and raises public health issues. The objective of this study was to determine the prevalence of anti-HHV-8 in selected populations of persons or patients with or without risk factors for the transmission of viral infections, in order to determine the routes of HHV-8 transmission. STUDY DESIGN AND METHODS: A total of 1431 persons or patients at low or high risk of sexually, blood-, or graft-transmitted viral infections were tested by means of a standardized immunofluorescence serologic assay detecting anti-HHV-8. RESULTS: The persons or patients could be classified into three distinct groups according to anti-HHV-8 prevalence: a low prevalence group (0.0% to 5.0%), including healthy blood donors, healthy pregnant women, multiply transfused patients with thalassemia major, and IV drug users; an intermediate prevalence group (5.0% to 20.0%), including organ donors, kidney transplant recipients, and multiply transfused patients with sickle cell disease; a high prevalence group (>20.0%), including HIV-negative persons at high risk of sexually-transmitted viral infections, and HIV-infected homosexual men and heterosexuals. CONCLUSION: The sexual route appears to be the main route of HHV-8 transmission; bloodborne transmission of HHV-8, if it exists, is rare. In contrast, organ transplantation recipients might be exposed to HHV-8 transmission by the transplanted organ, which raises the issue of systematic screening of organ donors.

Dengue fever: a harmful disease in patients with thrombocytopenia?

We describe 2 patients with autoimmune thrombocytopenic disease who developed classic dengue fever associated with serious bleeding and extremely low platelet counts (1000 cells/mm(3) and 3000 cells/mm(3), respectively). Such patients should be properly advised as to the possibility that common dengue fever may substantially enhance their risk for hemorrhagic complications.

Serological, epidemiological, and molecular differences between human T-cell lymphotropic virus Type 1 (HTLV-1)-seropositive healthy carriers and persons with HTLV-I Gag indeterminate Western blot patterns from the Caribbean.

To investigate the significance of serological human T-cell lymphotropic virus type 1 (HLTV-1) Gag indeterminate Western blot (WB) patterns in the Caribbean, a 6-year (1993 to 1998) cross-sectional study was conducted with 37,724 blood donors from Guadeloupe (French West Indies), whose sera were routinely screened by enzyme immunoassay (EIA) for the presence of HTLV-1 and -2 antibodies. By using stringent WB criteria, 77 donors (0.20%) were confirmed HTLV-1 seropositive, whereas 150 (0.40%; P < 0.001) were considered HTLV seroindeterminate. Among them, 41.3% (62) exhibited a typical HTLV-1 Gag indeterminate profile (HGIP). Furthermore 76 (50.7%) out of the 150 HTLV-seroindeterminate subjects were sequentially retested, with a mean duration of follow-up of 18.3 months (range, 1 to 70 months). Of these, 55 (72.4%) were still EIA positive and maintained the same WB profile whereas the others became EIA negative. This follow-up survey included 33 persons with an HGIP. Twenty-three of them (69.7%) had profiles that did not evolve over time. Moreover, no case of HTLV-1 seroconversion could be documented over time by studying such sequential samples. HTLV-1 seroprevalence was characterized by an age-dependent curve, a uniform excess in females, a significant relation with hepatitis B core (HBc) antibodies, and a microcluster distribution along the Atlantic coast of Guadeloupe. In contrast, the persons with an HGIP were significantly younger, had a 1:1 sex ratio, did not present any association with HBc antibodies, and were not clustered along the Atlantic façade. These divergent epidemiological features, together with discordant serological screening test results for subjects with HGIP and with the lack of HTLV-1 proviral sequences detected by PCR in their peripheral blood mononuclear cell DNA, strongly suggest that an HGIP does not reflect true HTLV-1 infection. In regard to these data, healthy blood donors with HGIP should be reassured that they are unlikely to be infected with HTLV-1 or HTLV-2.

Human T-lymphotropic virus type I among blood donors from Guadeloupe: donation, demographic, and biologic characteristics.

BACKGROUND: Epidemiologic data on human T-lymphotropic virus type I (HTLV-I) in Guadeloupe (French West Indies) are scant. STUDY DESIGN AND METHODS: From January 1989 to December 1996, 59,426 blood donors were screened by enzyme immunoassay for antibodies to HTLV-I. All repeatedly reactive samples were confirmed by Western blot. Temporal trends in HTLV-I seropositivity rates were examined during the study period. A multivariate analysis of donation, demographic, and biologic characteristics was performed. RESULTS: Of the screened blood donors, 195 were confirmed as seropositive, for an overall prevalence of 0.33 percent (95% CI 0.28-0.38). A marked decrease in overall HTLV-I prevalence with time (from 0.47% in 1989 to 0.13% in 1996) was observed, which can be explained mainly by the decreasing percentage of recruited new donors during the study period. Four independent risk factors for HTLV-I were identified: new donor status (odds ratio [OR] 12.5), female sex (OR 1.7), increasing age (30-39 years: OR, 2.4; 40-49 years: OR, 3.7; >50 years: OR 6.6), and positive antibodies to hepatitis B virus core antigen (OR, 1.7). Selection of specific locations for blood collection was inversely associated with HTLV-I (OR 0.5). CONCLUSION: New donor status, advancing age, female sex, and positivity for hepatitis B virus core antibodies were the major factors associated with HTLV-I infection in Guadeloupe.

Geographical clustering of human T-cell lymphotropic virus type I in Guadeloupe, an endemic Caribbean area.

Between January 1989 and December 1996, 59,426 blood donors from Guadeloupe (French West Indies) were screened for antibodies to human T-cell lymphotropic virus type I (HTLV-I). Of these, 195 were confirmed as being positive for HTLV-I, yielding an overall prevalence of 0.33% [95% confidence interval (CI) 0.28-0.38]. On multiple logistic regression analysis, risk factors for HTLV-I were female gender [odds ratio (OR) 1.8; CI 1.3-2.4], increasing age (30-39 years, OR 2.2, CI 1.4-3.4; 40-49 years, OR 3.1, CI 2.1-4.7; > or =50 years, OR 5.6, CI 3.6-8.6) and positive hepatitis B core antibodies (OR 2.0; CI 1.5-2.8). HTLV-I seropositivity was also significantly associated with current residence in certain areas, highlighting microgeographic clustering: individuals living along the Atlantic Facade of Guadeloupe, which is a traditional sugar cane plantation area where Africans were brought during slave trading, were at increased risk for HTLV-I infection (OR 1.9; CI 1.3-2.7) compared with other areas in Guadeloupe devoted to other activities. Our report of HTLV-I cluster identification in Guadeloupe probably reflects both its low spread and its highly intrafamilial restricted transmission within this endemic Caribbean population.

The endogenous benzodiazepine receptor ligand ODN increases cytosolic calcium in cultured rat astrocytes.

We have investigated the production of diazepam-binding inhibitor (DBI)-related peptides by astrocytes in primary culture and we have determined the effect of the octadecaneuropeptide DBI[33-50] (ODN) on the intracellular calcium concentration ([Ca2+]i) in astrocytes. Immunocytochemical labeling with antibodies against ODN showed that cultured astrocytes retain their ability to synthesize DBI in vitro. Cultured astrocytes were also found to release substantial amounts of ODN-immunoreactive material, and a brief exposure of astrocytes to a depolarizing potassium concentration resulted in a 5-fold increase in the rate of release of the ODN-like peptide. Microfluorimetric measurement of [Ca2+]i with the fluorescent probe indo-1 showed that nanomolar concentrations of ODN induced a marked increase in [Ca2+]i. The stimulatory effect of ODN on [Ca2+]i was not affected by calcium channel blockers or by incubation in Ca(2+)-free medium. In contrast, thapsigargin, an inhibitor of microsomal Ca(2+)-ATPase activity, totally abolished the ODN-induced increase in [Ca2+]i. Repeated pulses of ODN caused attenuation of the response, indicating the existence of a desensitization phenomenon. Preincubation of astrocytes with pertussis toxin totally blocked the effect of ODN on [Ca2+]i. The present study indicates that ODN-related peptides are synthesized and released by glial cells. Our results also show that synthetic ODN induces calcium mobilization from an intracellular store through stimulation of pertussis toxin-sensitive G protein. Taken together, these data suggest that endozepines act as paracrine and/or autocrine factors controlling the activity of astroglial cells.