Human papillomavirus genotype prevalence and distribution among Moroccan women

Background:Human papillomavirus (HPV) is the major etiologic agent of invasive cervical cancer, vulvar and vaginal cancer. It has been estimated that, worldwide, 70% of cervical cancers are due to HPV-16 and HPV-18. Malignant transformation appears to require the presence of additional cofactors such as pregnancy, smoking and immunosuppression. The aim of the present study was to determine the prevalence and distribution of HPV genotypes among Moroccan women.  Methods:Between January 1, 2011, and December 31, 2012, 277 cervical samples collected from confirmed women who attended the department of gynecology and obstetrics at Mohamed V Military teaching hospital, Rabat, Morocco, were analyzed in the laboratory of virology for HPV in vitro diagnosis and genotyping and for cytology in laboratory of pathology.Results:High-risk HPV DNA was detected in 101 (36%) samples, with higher prevalence in women ≥45 (43%) years. The overall prevalence of HPV infection and multiple infections in the study samples was 76% and 21%, respectively. The most frequent HPV genotypes were HPV-16 (31%). Human papillomavirus DNA detection was inversely related to maternal age. The risk of HPV infection was significantly reduced in women aged older than 30 years. The history of gynaecological problem showed significant association with the HPV positive test.Conclusion:In Morocco, the diagnosis of cervical lesions rests exclusively on the cytology-based screening that offers substantial protection, although current coverage is low. The introduction of HPV DNA testing in cervical cancer management will greatly benefit early stage HPV detection and help prevent development of cervical lesions and cancer. Screening pregnant women offer a significant opportunity for the Moroccan National Program against cervical cancer to control.  

Occult hepatitis B virus infection in Moroccan HIV infected patients

Background: The purpose of this study is to assess the prevalence of Occult hepatitis B virus Infection (OBI) among antiretroviral treatment naïve HIV-1 infected individuals in Morocco and to determine factors favouring its occurrence.Methods: The retrospective study was conducted in the Mohammed V military teaching hospital in Rabat between January 2010 and June 2011. It included patients with confirmed HIV infection, tested negative to serological detection of HBV surface antigen (HBsAg) and did not received antiviral treatment or hepatitis B vaccine. All samples were tested for anti-HBc, anti-HBs and anti-HCV antibodies using enzyme immunoassay (ELISA). The detection of HBV DNA was performed by real-time PCR using two specific primers for a gene in the region C of the viral genome. The sensitivity of the technique was 20 copies/ml.Results: A total of 82 samples were analyzed, 19 (23 %) were found to have isolated anti-HBc, 07 (8.5%) with associated anti-HBc and Anti-HBs. No anti-HCV marker was detected on these screening samples. The HBV DNA was detected in 48 (58%) samples, of which, males constituted 58% (28/48). The mean age of these patients was 38 ± 8.2 (29-56), the median HIV-1 viral load and CD4 cell count HIV-1 infected patients were 127500 (54108-325325) copies/ml and 243 [80-385] cells/mm3 respectively and 27.1% (13/48) of these patients were found to have isolated anti-HBc. A significant correlations between DNA HBV and HIV viral load higher than 100000 copies/ml (P = 0.004), CD4 cell count lower than 400 cells/mm3 (P = 0.013, P = 0.006) and isolated anti-HBc samples (P <0.005) were founded. However there was no significant association with age, sex, transmission mode and clinical stage.  Conclusion: The consequences of this high prevalence of OBI in Morocco need to be considered in laboratory diagnosis of HBV infection in HIV infected patients and the PCR seems to be inevitable for a better diagnosis and therapy.

HLA-B*44 allele associated with clinical parameters in HIV-1 infected Moroccan cohort

Background: The human leukocyte antigen-B*44 (HLA-B*44) allele has been reported to have promising results in the control of human immunodeficiency virus-1 (HIV-1) infection and associated with protection against HIV-1 disease progression. In the Moroccan HIV-1 infected patients, the contribution of this allele has not been established. This study aimed to evaluate the distribution of HLA-B*44 allele among HIV-1-infected in Morocco. Additionally, investigate HLA-B*44 allele association with demographical and HIV clinical parameters.Methods: One hundred and sixty-seven HIV-1 infected, antiretroviral naive individuals were enrolled in this study. The HLA-B*44 allele screening was performed using the PCR amplification.Results: Of the 167 individuals genotyped, 26 (16%) of them expressing the HLA-B*44 allele. Clinical stages at diagnosis, median pre-treatment HIV viral load (pVL) and CD4 T cell counts differ significantly (p = 0.0001, p=0.001 and p=0.0001 respectively) between the patients who had been expressing the HLA-B*44 allele and patients who had not been expressing this allele. The presence of HLA-B*44 allele was significantly associated with pVL and CD4 T cell counts (p=0.004 and p=0.0001 respectively). The bivariate analysis has showed that the expression of the HLA-B*44 allele was strongly associated with advanced HIV infection (Odd ratio (OR) 0.12 (95% confidence interval (CI) 0.04-0.37), p=0.0001).Conclusions: Author have described for the first time in Morocco the association of the HLA-B*44 allele with the clinical parameters of HIV infection. These results expand the knowledge of the distribution and effect of this allele in the Moroccan population

Recurrence of occult hepatitis B virus infection in a recipient of a liver transplant for HCV-related cirrhosis: full length genome, mutations analysis and literature review

The outcome of liver transplant recipients in HCV chronic carriers with Anti-HBc only concerning occult HBV infection is unknown. We report here the case of a patient who underwent liver transplantation (LT) for cirrhosis post chronic hepatitis C who received an allograft from a donor with no marker of hepatitis B infection. After LT, HBV DNA was detected in the serum in the absence of HBsAg while HCV RNA remained negative. To determine the origin of this occult HBV infection, we retrospectively examined stored serum and liver tissue, pre and post-transplantation, for HBV DNA by PCR. A stored liver biopsy of the donor before transplantation was also tested. HBV DNA was detected in the pre-transplant liver but not in the donor liver. HBV viral load quantified by real time PCR after LT ranged from about 102 to 5x103 HBV DNA copies/mg of liver, while in sera, concentrations ranged from 102 to 3x103 HBV DNA copies/ml. All PCR products in the S gene from liver and sera were sequenced. Analysis of sequences showed the presence of an HBV strain genotype D. The nucleotide homology between the patient’s HBV strains before and after LT was 96 % across the analyzed regions. Full length HBV genomes were amplified from the sera using Rolling Circle Amplification and then sequenced. Analysis of sequences confirmed the genotype D, but did not show obvious mutations that could contribute to HBsAg seronegativity and low HBV viral replication. Factors leading to occult HBV infection are still unclear, but it is well establish that occult HBV infection is frequent in HCV patients. This underlines the role of extra hepatic sites for HBV replication, potentially lymphocytes acting as “reservoirs”.  

Caractérisation moléculaire des infections à VHB occultes au cours des hépatites C chroniques

L infection par le virus de l hépatite B occulte, définie par la présence de l ADN du VHB en l absence d AgHBs dans le sérum, a été retrouvée de manière fréquente dans les hépatites C chroniques. Afin de mieux cerner les mécanismes d échappement du VHB occulte aux tests diagnostiques classiques et de déterminer les conséquences de cette co-infection sur l évolution de l hépatite C chronique, nous avons analysé, par des techniques moléculaires très sensibles développées au laboratoire, les sérums de 203 patients atteints d hépatite C chroniques avant qu ils ne soient traités. Les résultats de cette première étude ont montré que la prévalence des infections occultes chez les patients porteurs chroniques du VHC pourrait atteindre 20% en France et que la présence de l infection à VHB occulte est associée à une mauvaise réponse au traitement ainsi qu à l aggravation des lésions hépatiques et à l accélération de l évolution vers l hépatocarcinome. Afin de permettre la caractérisation moléculaire du VHB occulte, le génome entier a été amplifié, puis cloné et séquencé dans le cas particulier d un patient VHC transplanté. L analyse des différents clones n a pas montré les mutations connues susceptibles d expliquer l absence de détection de l AgHBs. Ces résultats suggèrent d une part, l implication d autres facteurs dans la suppression de la réplication et l altération de l expression du VHB, d autre part, l importance des sites extrahépatiques dans l infection à VHB occulte. Ces travaux soulignent la nécessité de développer de nouvelles approches diagnostiques et thérapeutiques dans la prise en charge du VHB occulte et particulièrement dans les co-infections avec le VHCOccult Hepatitis B infection (HBV), defined by HBV DNA positivity in absence of HBsAg in the serum was found in 30% of hepatitis of unknown aetiology and frequently among HCV chronic carriers. In order to better understand how HBV escape to diagnosis tests and determine the consequences of this co-infection on HCV chronic infection, we analyzed by ultra sensitive molecular tests developed in the lab, serum samples from 203 HCV chronic carriers before any antiviral treatment. The results from this first study showed that occult HBV infection frequency could reach 20% in France and that occult HBV infection may worsen the course of HCV infection being associated to a bad response to antiviral therapy and aggravation of liver disease. In order to perform the molecular characterization of hepatitis B viruses in cases of occult HBV infections, the whole HBV genome was amplified by a new technique developed in the lab, named Rolling Cycle Amplification (RCA), cloned and sequenced in a HCV transplanted case. The analysis of the cloned sequences did not show the presence of any of the known mutations in the viral genome that may explain HBsAg negativity. Our results suggest, on one hand, the implication of other factors in the suppression of the HBV replication and altered expression of HBV, on the other hand, the importance of extra hepatic sites of HBV replication during occult HBV infections, since it was able to persist after liver transplantation. Our work emphasise the need to develop new diagnostic and therapeutic tools in the case of occult HBV infections especially during co-infection with HCVLYON1-BU.Sciences (692662101) / SudocSudocFranceF

What is really ongoing during occult HBV reactivation?

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Prevalence of resistance to integrase strand-transfer inhibitors (INSTIs) among untreated HIV-1 infected patients in Morocco

Abstract Objective The integrase strand-transfer inhibitors (INSTIs) are an important class in the arsenal of antiretroviral drugs designed to block the integration of HIV-1 cDNA into the host DNA through the inhibition of DNA strand transfer. In this study for the first time in Morocco, the complete HIV-1 integrase gene was analysed from newly diagnosed patients to evaluate the prevalence of natural polymorphisms and INSTIs resistance-associated mutations in the integrase gene. Results The 864pb IN coding region was successfully sequenced from plasma sample for 77 among 80 antiretroviral naïve patients. The sequences were interpreted for drug resistance according to the Stanford algorithm. Sixty samples were HIV-1 subtype B (78%), fourteen CRF02_AG (18%), two subtype C and one subtype A. Overall 81 of 288 (28%) amino acid IN positions presented at least one polymorphism each. We found 18 (36.73%), 42 (25.76%) and 21 (27.27%) of polymorphic residues assigned to the N-Terminal Domain, Catalytic Core Domaine and the C-Terminal Domain positions respectively. Primary INSTIs resistance mutation were absent, however secondary mutations L74IM, T97A were detected in four samples (5.2%). These results demonstrate that untreated HIV-1 infected Moroccans will be susceptible to INSTIs

MOESM1 of Prevalence of resistance to integrase strand-transfer inhibitors (INSTIs) among untreated HIV-1 infected patients in Morocco

Additional file 1. Distribution of IN mutations in subtypes B and non-B in therapy-naĂŻve patients. Secondary and additional mutations screened in 17 positions (V72I, T112I, S119PRTG, T124A, T125K, A128T, Q146K, M154I, K156N, V165I, V201I, I203M, T206S, S230N, D232N, V249I and C280Y) using the Stanford HIV Drug Resistance Program (Version September 23, 2016), all mutations identified in this study are likely natural polymorphisms