Etiology of hepatocellular carcinoma in West Africa, a case-control study.

Hepatocellular carcinoma (HCC) is a leading cause of cancer in West Africa where HBV infection is endemic. However, limited information is available on other risk factors such as alcohol use, HCV and HIV infection. A case-control study was conducted in referral hospitals of Abidjan (Cote d'Ivoire), Bamako (Mali) and Lome (Togo). Cases were matched with controls on age, gender and participating site. The diagnosis of HCC relied on the combination of one or more space-occupying lesions suggestive of an HCC on a standardized abdominal ultrasound and an α-fetoprotein level ≥400 ng/ml. HIV, HBV and HCV serology were performed. Hazardous alcohol use was assessed using the AUDIT questionnaire. A conditional logistic regression model was used to measure odds ratio (OR) with their 95% confidence intervals (CI). A total of 160 cases and 320 controls were included. Cases were predominantly men (80.0%) with a median age of 47 years (IQR 38-57). Hazardous alcohol use (OR = 4.5 [CI 1.1-18.5]), HBV infection (OR = 62.5 [CI 20.5-190.7]) and HCV infection OR = 35.9 [CI 10.0-130.3]) were independently associated with HCC. Combining the effect of HBV infection and alcohol, HBV-infected hazardous drinkers had an OR = 149.8 (CI 13.5-1 667.0), HBV mono-infected had an OR = 57.4 (CI 18.8-175.3) (ref: HBV-negative). Aside the independent association of alcohol use and HBV and HCV infection with HCC, a synergic effect between alcohol use and HBV infection was identified. Timely screening and care of HBV infection and hazardous drinking might prevent a significant number of HCC in West Africa.

Molecular characteristics of Hepatitis B and chronic liver disease in a cohort of HB carriers from Bamako, Mali.

BACKGROUND: Hepatitis B (HB) infection is common in Mali. However, there is little information on molecular and biochemical characteristics of HB carriers. METHODS: A group of 1466 adult volunteers was recruited in the district of Bamako. Confirmed HB carriers were tested for HB viral load by quantitative PCR and HBV was genotyped by sequencing of HBS. Fibrosis and hepatitis activity were measured using the Fibrotest-Actitest. A mutation of TP53 at codon 249 (R249S), specific for exposure to aflatoxin, was detected in cell-free DNA extracted from plasma. RESULTS: Overall, 276 subjects were HBsAg-positive (18.8%). Among 152 subjects tested for HBV load, 49 (32.2%) had over 10(4) copies/mL and 16 (10.5%) had levels below the limit of detection. The E genotype was found in 91.1% of carriers. Fibrotest scores ≥ F2 were observed in 52 subjects (35.4%). Actitest scores ≥ A2 were detected in 15 subjects (10.2%) and were correlated with Fibrotest scores (p = 0.0006). Among 105 subjects tested, 60% had detectable levels of R249S copies (>40 copies/mL plasma). CONCLUSION: Chronic HB carriage in adults in Bamako district is well over epidemic threshold. About 1/3 of carriers have moderate to severe liver fibrosis and 60% have detectable aflatoxin-related TP53 R249S mutation. These results support introduction of anti-HB therapies to reduce the progression towards severe liver disease.

Implementation of Kidney Biopsy in One of the Poorest Countries in the World: Experience from Zinder Hospital (Niger).

Kidney biopsy (KB) has become essential in the nephrologist's approach to kidney diseases, both for diagnosis, treatment, and prognosis. Our objective is to describe the preliminary results of KBs in Niger, one of the poorest countries in the world. This is a descriptive cross-sectional study that took place over 36 months in the nephrology/dialysis department of the Zinder National Hospital. Biopsy results were obtained in less than 5 working days. Patients were responsible for covering the cost of the kidney biopsy. The data collected were analyzed using Epi Info V7 software. We performed 120 kidney biopsies during the study period. The average age of the patients was 35 years ± 15.4 [5-68]. The male/female sex ratio was 2:1. Patients' medical history included herbal medicine use in 33% of cases and high blood pressure in 27.5% of cases. Proteinuria was present at a rate of ≥3 g/24 h in 46.6% of them. The primary indication for kidney biopsy was glomerular syndrome in 62.5% of cases, including 50% with nephrotic syndrome. All kidney biopsies were performed with real-time ultrasound guidance, using an automatic gun fitted with a 16G needle. Regarding complications, macroscopic hematuria was present in 12.5% of cases. Inadequate kidney biopsy was infrequent (5.8% of cases). The most common findings were (i) glomerular diseases (58.4%), such as membranoproliferative glomerulonephritis (13.3%), focal-segmental glomerulosclerosis (10.6%), lupus nephritis (8.8%), minimal change disease (8%), and membranous nephropathy (2.7%), and (ii) tubulointerstitial changes (31.8%). Diabetic nephropathy was rare (2.6%), as was IgA nephropathy (0.9%). We have demonstrated that implementing a sustainable kidney biopsy program in a very poor country is feasible, thanks to the dedication of a specialized renal pathologist. Having a clear diagnosis can assist in properly treating these renal patients according to international guidelines, thereby delaying the progression to end-stage kidney disease.

Status Report of Renal Transplant Patients in Niger.

BACKGROUND: Kidney transplantation is the treatment of choice for end-stage chronic kidney disease. It improves quality of life and increases life expectancy. At present, Niger is one of the poorest countries in the world does not practice kidney transplantation; thus, patients continue to be referred to other countries for transplantation. METHODS: This descriptive cross-sectional study was carried out at the Nephrology Department of the National Hospital Amirou Boubacar Diallo in Niamey, Niger over a 5-month period. It included all patients that had benefited from kidney transplantation with the aim to evaluate patient and graft survival. RESULTS: We identified 25 patients. The male to female ratio was 2:1. The average age was 45.4 years ± 11.1 years. The average age of donors was 36.1 years ± 12.6 years with a clear male predominance (17 males to 8 females); all of them were related-donors with 72% of them being brothers or sisters. The causative nephropathy was undetermined in 80% of patients. Sixty-four percent of patients had their kidney transplant in Maghreb, including 16% in Tunisia. The complications were mostly medical (68%), as 20% were immunologic; 8% infectious; 16% metabolic; 20% cardiovascular, and 4% were related to recurrence of the initial nephropathy. Surgical complications involved 6 patients (24%): 5 were vascular cases and one was a urological case. With a median follow-up of 5 years, the patients' survival was 84%, the graft survival was 56%, and death-censored graft survival was 67%. CONCLUSION: In Niger, after kidney transplantation, the patients' survival is satisfactory, whereas the graft survival is not, mostly due to inadequate follow-up check-ups and prohibitive prices of immunosuppressants.

Characterization of HIV-1 antiretroviral drug resistance after second-line treatment failure in Mali, a limited-resources setting.

OBJECTIVES: We describe the outcomes of second-line drug resistance profiles and predict the efficacy of drugs for third-line therapy in patients monitored without the benefit of plasma HIV-1 RNA viral load (VL) or resistance testing. METHODS: We recruited 106 HIV-1-infected patients after second-line treatment failure in Mali. VL was determined by the Abbott RealTime system and the resistance by the ViroSeq HIV-1 genotyping system. The resistance testing was interpreted using the latest version of the Stanford algorithm. RESULTS: Among the 106 patients, 93 had isolates successfully sequenced. The median age, VL and CD4 cells were respectively 35 years, 72 000 copies/mL and 146 cells/mm(3). Patients were exposed to a median of 4 years of treatment and to six antiretrovirals. We found 20% of wild-type viruses. Resistance to etravirine was noted in 38%, to lopinavir in 25% and to darunavir in 12%. The duration of prior nucleos(t)ide reverse transcriptase inhibitor exposure was associated with resistance to abacavir (P < 0.0001) and tenofovir (P = 0.0001), and duration of prior protease inhibitor treatment with resistance to lopinavir (P < 0.0001) and darunavir (P = 0.06). CONCLUSION: Long duration of therapy prior to failure was associated with high levels of resistance and is directly related to limited access to VL monitoring and delayed switches to second-line treatment, precluding efficacy of drugs for third-line therapy. This study underlines the need for governments and public health organizations to recommend the use of VL monitoring and also the availability of darunavir and raltegravir for third-line therapies in the context of limited-resource settings.

Low retention of HIV-infected patients on antiretroviral therapy in 11 clinical centres in West Africa.

OBJECTIVE: To study factors associated with the probability of retention in antiretroviral therapy (ART) programmes in West Africa. METHODS: The International epidemiologic Databases to Evaluate AIDS (IeDEA) in West Africa is a prospective, operational, observational cohort study based on collaboration between 11 cohorts of HIV-infected adult patients in Benin, Côte d'Ivoire, Gambia, Mali and Senegal. All patients aged 16 and older at ART initiation, with documented gender and date of ART initiation, were included. For those with at least 1 day of follow-up, Kaplan-Meier method and Weibull regression model were used to estimate the 12-month probability of retention in care and the associated factors. RESULTS: In this data merger, 14 352 patients (61% female) on ART were included. Median age was 37 (interquartile range (IQR): 31-44 years) and median CD4 count at baseline was 131 cells/mm(3) (IQR: 48-221 cells/mm(3)). The first-line regimen was NNRTI-based for 78% of patients, protease inhibitor-based for 17%, and three NRTIs for 3%. The probability of retention was 0.90 [95% confidence interval (CI): 0.89-0.90] at 3 months, 0.84 (95% CI: 0.83-0.85) at 6 months and 0.76 (95% CI: 0.75-0.77) at 12 months. The probability of retention in care was lower in patients with baseline CD4 count <50 cells/mm(3) [adjusted hazard ratio (aHR) = 1.37; 95% CI: 1.27-1.49; P < 0.0001] (reference CD4 > 200 cells/mm(3), in men (aHR = 1.17; 95% CI: 1.10-1.24; P = 0.0002), in younger patients (<30 years) (aHR = 1.10; 95% CI: 1.03-1.19; P = 0.01) and in patients with low haemoglobinaemia <8 g/dl (aHR = 1.33; 95% CI: 1.21-1.45; P < 0.0001). Availability of funds for systematic tracing was associated with better retention (aHR = 0.29; 95% CI: 0.16-0.55; P = 0.001). CONCLUSIONS: Close follow-up, promoting early access to care and ART and a decentralized system of care may improve the retention in care of HIV-infected patients on ART.

Incidence of Severe Neutropenia in HIV-Infected People Starting Antiretroviral Therapy in West Africa.

BACKGROUND: In sub-Saharan Africa, antiretroviral therapy (ART) including drugs with potential toxicity such as Zidovudine (ZDV) are routinely prescribed. This study aimed at estimating the incidence of severe neutropenia and associated factors after ART initiation in five West African countries. METHODS: A retrospective cohort analysis was conducted within the international epidemiologic database to evaluate AIDS (IeDEA) collaboration in West Africa. All HIV-infected adults, initiating ART between 2002 and 2014, with a baseline and at least one follow-up absolute neutrophil count (ANC) measurement were eligible. Incidence of severe neutropenia (ANC <750 cells/mm3) was estimated with 95% confidence interval (CI) according to age, gender, HIV clinic, hemoglobin, CD4 count, clinical stage, and ART duration. A Cox proportional hazard model was used to identify factors associated with severe neutropenia, expressed with their adjusted hazard ratios (aHR). RESULTS: Between 2002 and 2014, 9,426 HIV-infected adults were enrolled. The crude incidence rate of a first severe neutropenia was 9.1 per 100 person-years (95% CI: 8.6-9.8). Factors associated with severe neutropenia were exposure to ZDV <6 months (aHR = 2.2; 95% CI: 1.8-2.6), ≥6-12 months (aHR = 2.1; 95% CI: 1.6-2.8) and ≥12 months (aHR = 1.6; 95% CI: 1.2-2.2) [Ref. no ZDV exposure], CD4 count <350 cells/mm3 (aHR = 1.3; 95% CI: 1.1-1.5) and advanced clinical stage at ART initiation (aHR = 1.2; 95% CI: 1.0-1.4). CONCLUSION: The incidence of severe neutropenia after ART initiation in West Africa is high and associated with ZDV exposure and advanced HIV disease. In this context, efforts are needed to scale-up access to less toxic first-line ART drugs and to promote early ART initiation.

[Case-control study of hepatitis C HBs Ag and antivirus antibodies in chronic hepatopathies]. / Etude de l'antigène HBs et des anticorps antivirus de l'hépatite C au cours des hépatopathies chroniques.

The aim of this study is to establish the prevalence of hepatitis C HBs Ag and of anti-virus antibodies in chronic hepatopathies. The prospective case-control study was carried out on 91 patients who needed to be treated for chronic hepatopathies and 92 occasional blood donors. The search for hepatitis C HBs Ag and anti-virus antibodies was done using third generation ELISA screening. At the end of the study, HBs Ag was found in 54% of the patients vs. 4.3% of the control (p=0.0006). The two markers were present more frequently in cirrhosis than in hepatocellular carcinoma (HCC) and their association was more frequent in the case of cirrhosis. In Mali, hepatitis B and C viruses play an important part in chronic hepatopathies.

Disease patterns and causes of death of hospitalized HIV-positive adults in West Africa: a multicountry survey in the antiretroviral treatment era.

OBJECTIVE: We aimed to describe the morbidity and mortality patterns in HIV-positive adults hospitalized in West Africa. METHOD: We conducted a six-month prospective multicentre survey within the IeDEA West Africa collaboration in six adult medical wards of teaching hospitals in Abidjan, Ouagadougou, Cotonou, Dakar and Bamako. From April to October 2010, all newly hospitalized HIV-positive patients were eligible. Baseline and follow-up information until hospital discharge was recorded using standardized forms. Diagnoses were reviewed by a local event validation committee using reference definitions. Factors associated with in-hospital mortality were studied with a logistic regression model. RESULTS: Among 823 hospitalized HIV-positive adults (median age 40 years, 58% women), 24% discovered their HIV infection during the hospitalization, median CD4 count was 75/mm(3) (IQR: 25-177) and 48% had previously received antiretroviral treatment (ART). The underlying causes of hospitalization were AIDS-defining conditions (54%), other infections (32%), other diseases (8%) and non-specific illness (6%). The most frequent diseases diagnosed were: tuberculosis (29%), pneumonia (15%), malaria (10%) and cerebral toxoplasmosis (10%). Overall, 315 (38%) patients died during hospitalization and the underlying cause of death was AIDS (63%), non-AIDS-defining infections (26%), other diseases (7%) and non-specific illness or unknown cause (4%). Among them, the most frequent fatal diseases were: tuberculosis (36%), cerebral toxoplasmosis (10%), cryptococcosis (9%) and sepsis (7%). Older age, clinical WHO stage 3 and 4, low CD4 count, and AIDS-defining infectious diagnoses were associated with hospital fatality. CONCLUSIONS: AIDS-defining conditions, primarily tuberculosis, and bacterial infections were the most frequent causes of hospitalization in HIV-positive adults in West Africa and resulted in high in-hospital fatality. Sustained efforts are needed to integrate care of these disease conditions and optimize earlier diagnosis of HIV infection and initiation of ART.

Effect of seasonality and ecological factors on the prevalence of the four malaria parasite species in northern mali.

Background. We performed 2 cross-sectional studies in Ménaka in the Northeastern Mali across 9 sites in different ecological settings: 4 sites have permanent ponds, 4 without ponds, and one (City of Ménaka) has a semipermanent pond. We enrolled 1328 subjects in May 2004 (hot dry season) and 1422 in February 2005 (cold dry season) after the rainy season. Objective. To examine the seasonality of malaria parasite prevalence in this dry northern part of Mali at the edge of the Sahara desert. Results. Slide prevalence was lower in hot dry than cold dry season (4.94 versus 6.85%, P = 0.025). Gametocyte rate increased to 0.91% in February. Four species were identified. Plasmodium falciparum was most prevalent (74.13 and 63.72%). P. malariae increased from 9.38% to 22.54% in February. In contrast, prevalence of P. vivax was higher (10.31%) without seasonal variation. Smear positivity was associated with splenomegaly (P = 0.007). Malaria remained stable in the villages with ponds (P = 0.221); in contrast, prevalence varied between the 2 seasons in the villages without ponds (P = 0.004). Conclusion. Malaria was mesoendemic; 4 species circulates with a seasonal fluctuation for Plasmodium falciparum.

Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity.

Mutations in the connection domain (CD) of reverse transcriptase have been implicated in reverse transcriptase inhibitor (RTI) resistance, but this is controversial and little is known in non-B subtype HIV-1. We determined CD mutations prevalence in a population infected predominantly with CRF02_AG and investigated associations with phenotypic RTI resistance. Detected CD mutations were G335D (82.3%), A371V (69.8%), E399D (9.4%), N348I (5.2%), V365I (4.2), Y318F (2.1%), G333E (2.1%), and A360V (2.1%). Mutations were largely polymorphic and did not confer RTI resistance. The observed trend toward reduced likelihood of etravirine or nevirapine resistance in the presence of G335D should be investigated further.

First-year lymphocyte T CD4+ response to antiretroviral therapy according to the HIV type in the IeDEA West Africa collaboration.

OBJECTIVE: To compare the lymphocyte T CD4+ (CD4) response to combinations of antiretroviral therapy (ART) in HIV-1, HIV-2 and dually positive patients in West Africa. DESIGN AND SETTING: Collaboration of 12 prospective cohorts of HIV-infected adults followed in Senegal (2), Gambia (1), Mali (2), Benin (1) and Côte d'Ivoire (6). SUBJECTS: Nine thousand, four hundred and eighty-two patients infected by HIV-1 only, 270 by HIV-2 only and 321 dually positive, who initiated an ART. OUTCOME MEASURES: CD4 change over a 12-month period. RESULTS: Observed CD4 cell counts at treatment initiation were similar in the three groups [overall median 155, interquartile range (IQR) 68; 249 cells/microl). In HIV-1 patients, the most common ART regimen was two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI; N = 7714) as well as for dually positive patients (N = 135). HIV-2 patients were most often treated with a protease inhibitor-based regimen (N = 193) but 45 of them were treated with an NNRTI-containing ART. In those treated with a NNRTI-containing regimen, the estimated mean CD4 change between 3 and 12 months was significantly lower in HIV-2 (-41 cells/microl per year) and dually positive patients (+12 cells/microl per year) compared to HIV-1 patients (+69 cells/microl per year, overall P value 0.01). The response in HIV-2 and dually positive patients treated by another regimen (triple NRTIs or protease inhibitor-containing ART) was not significantly different than the response obtained in HIV-1-only patients (all P values >0.30). CONCLUSION: An optimal CD4 response to ART in West Africa requires determining HIV type prior to initiation of antiretroviral drugs. NNRTIs are the mainstay of first-line ART in West Africa but are not adapted to the treatment of HIV-2 and dually positive patients.

Alcohol use and non-adherence to antiretroviral therapy in HIV-infected patients in West Africa.

AIM: To investigate the association between alcohol use and adherence to highly active antiretroviral treatment (HAART) among human immunodeficiency virus (HIV)-infected patients in sub-Saharan Africa. DESIGN AND SETTING: Cross-sectional survey conducted in eight adult HIV treatment centres from Benin, Côte d'Ivoire and Mali. Participants and measurements During a 4-week period, health workers administered the Alcohol Use Disorders Identification Test to HAART-treated patients and assessed treatment adherence using the AIDS Clinical Trials Group follow-up questionnaire. FINDINGS: A total of 2920 patients were enrolled with a median age of 38 years [interquartile range (IQR) 32-45 years] and a median duration on HAART of 3 years (IQR 1-4 years). Overall, 91.8% of patients were identified as adherent to HAART. Non-adherence was associated with current drinking [odds ratio (OR) 1.4; 95% confidence interval (CI) 1.1-2.0], hazardous drinking (OR 4.7; 95% CI 2.6-8.6) and was associated inversely with a history of counselling on adherence (OR 0.7; 95% CI 0.5-0.9). CONCLUSIONS: Alcohol consumption and hazardous drinking is associated with non-adherence to HAART among HIV-infected patients from West Africa. Adult HIV care programmes should integrate programmes to reduce hazardous and harmful drinking.

Low prevalence of detectable HIV plasma viremia in patients treated with antiretroviral therapy in Burkina Faso and Mali.

BACKGROUND: Sub-Saharan Africa has seen dramatic increases in the numbers of people treated with antiretroviral therapy (ART). Although standard ART regimens are now universally applied, viral load measurement is not currently part of standard monitoring protocols in sub-Saharan Africa. METHODS: We describe the prevalence of inadequate virological response (IVR) to ART (viral load >or= 500 copies/mL) and identify factors associated with this outcome in 606 HIV-positive patients treated for at least 6 months. Recruitment took place in 7 hospitals and community-based sites in Bamako and Ouagadougou, and information was collected using medical charts and interviews. RESULTS: The overall prevalence of IVR in treatment-naive patients was 12.3% and 24.4% for pretreated patients. There were no differences in rates of IVR according to ART delivery sites and time on treatment. Patients living farther away [odds ratio (OR) = 2.48; 95% confidence interval (CI) 1.40 to 4.39], those on protease inhibitor or nucleoside reverse transcriptase inhibitor regimens (OR = 3.23; 95% CI 1.79 to 5.82) and those reporting treatment interruptions (OR = 2.36; 95% CI 1.35 to 4.15), had increased odds of IVR. Immune suppression (OR = 3.32, 95% CI 1.94 to 5.70) and poor self-rated health (OR = 2.00; 95% CI 1.17 to 3.41) were also associated with IVR. CONCLUSIONS: Sufficient expertise and dedication exist in public hospital and community-based programs to achieve rates of treatment success comparable to better-resourced settings.

Meningococcal meningitis in sub-Saharan Africa: the case for mass and routine vaccination with available polysaccharide vaccines.

Endemic and epidemic group A meningococcal meningitis remains a major cause of morbidity and mortality in sub-Saharan Africa, despite the availability of the safe and inexpensive group A meningococcal polysaccharide vaccine, which is protective at all ages when administered as directed. Despite optimal therapy, meningococcal meningitis has a 10% fatality rate and at least 15% central nervous system damage. WHO's policy of epidemic containment prevents, at best, about 50% of cases and ignores endemic meningitis, which is estimated at 50,000 cases per year. The effectiveness of group A, C, W135, and Y capsular polysaccharides is the basis for recommending universal vaccination with group A meningococcal polysaccharide twice in infancy, followed by the four-valent vaccine in children aged two and six years. This could eliminate epidemic and endemic disease, prepare for the use of conjugates when they become available, and probably could have prevented the recent epidemics of groups A and W135 meningitis in Burkina Faso.