Outcomes of a nine-month regimen for rifampicin-resistant tuberculosis up to 24 months after treatment completion in nine African countries.

BACKGROUND: Treatment outcomes of the shorter regimen for rifampicin-resistant tuberculosis are not completely established. We report on these outcomes two years after treatment completion among patients enrolled in an observational cohort study in nine African countries. METHODS: 1,006 patients treated with the nine-month regimen were followed every six months with sputum cultures up to 24 months after treatment completion. The risk of any unfavourable outcome, of failure and relapse, and of death during and after treatment was analysed according to patient's characteristics and initial drug susceptibility by Cox proportional hazard models. FINDINGS: Respectively 67.8% and 57.2% patients had >=1 culture result six months and 12 months after treatment completion. Fourteen relapses were diagnosed. The probability of relapse-free success was 79.3% (95% confidence interval [CI] 76.6-82.0%) overall, 80.9% (95% CI 78.0-84.0%) among HIV-negative and 72.5% (95% CI 66.5-78.9%) among HIV-infected patients. Initial fluoroquinolone (adjusted hazard ratio [aHR] 6.7 [95% CI 3.4-13.1]) and isoniazid resistance (aHR 9.4 [95% CI 1.3-68.0]) were significantly associated with increased risk of failure/relapse and of any unfavourable outcome. INTERPRETATION: The close to 80% relapse-free success indicates the good outcome of the regimen in low-and middle-income settings. Results confirm the lesser effectiveness of the regimen in patients with initial resistance to fluoroquinolones and support the use of high-dose isoniazid, but do not support exclusion of patients for resistance to drugs other than fluoroquinolones. FUNDING: Expertise-France and Agence Française de Développement.

[Epidemiological and clinical features of tuberculosis at the Hôpital de l'Amitié in Bangui]. / Aspects épidémiologiques et cliniques de la tuberculose en milieu hospitalier à Bangui.

Tuberculosis (TB) is endemic in the Central African Republic (CAR) with an incidence rate of 391 per 100,000 population in 2015. This study aims to analyze current epidemiological and clinical features of TB at the Hôpital de l'Amitié in the Central African Republic. We conducted an analytic retrospective study of patients hospitalized in the Department of Medicine at the Hôpital de l'Amitié from 15 April 2010 to 14 October 2011. Data were collected using a questionnaire and then analyzed with Epi info software 3.5.3. Chi-square test was used to compare proportions, using a threshold significance level of 5%. The study included 220 patients, of whom 128 were women (58.18%). The average age of patients was 35.69± 10.65 years. In 42.70% of cases, patients had no professional activity. Prevalence of tuberculosis in hospital was 10.99%. On average, 12 cases of TB were recorded each month. Most common clinical signs included: chronic cough (71.81%), fever (96.82%), alteration of the general state (91.36%) and pulmonary condensation syndrome (63.64%). The diseases most commonly associated with tuberculosis were HIV/AIDS (73.36%), malaria (48.63%) and anemia (31.81%). The mean time between symptom onset and diagnosis was 37.65 days. Mortality rate was 18.63%. TB/HIV co-infection and neuromeningeal TB were associated with a high mortality rate (p < 0.05). Tuberculosis is a common disease in Bangui and it is often associated with HIV infection. Prognosis is poor in the case of neuromeningeal involvement. Prevention and routine monitoring in HIV infected patients may contribute to reduce the extent and severity of TB.

Hepatitis B and hepatitis D virus infections in the Central African Republic, twenty-five years after a fulminant hepatitis outbreak, indicate continuing spread in asymptomatic young adults.

Hepatitis delta virus (HDV) increases morbidity in Hepatitis B virus (HBV)-infected patients. In the mid-eighties, an outbreak of HDV fulminant hepatitis (FH) in the Central African Republic (CAR) killed 88% of patients hospitalized in Bangui. We evaluated infections with HBV and HDV among students and pregnant women, 25 years after the fulminant hepatitis (FH) outbreak to determine (i) the prevalence of HBV and HDV infection in this population, (ii) the clinical risk factors for HBV and/or HDV infections, and (iii) to characterize and compare the strains from the FH outbreak in the 1980s to the 2010 HBV-HDV strains. We performed a cross sectional study with historical comparison on FH-stored samples (n = 179) from 159 patients and dried blood-spots from volunteer students and pregnant women groups (n = 2172). We analyzed risk factors potentially associated with HBV and HDV. Previous HBV infection (presence of anti-HBc) occurred in 345/1290 students (26.7%) and 186/870 pregnant women (21.4%)(p = 0.005), including 110 students (8.8%) and 71 pregnant women (8.2%), who were also HBsAg-positive (p = 0.824). HDV infection occurred more frequently in pregnant women (n = 13; 18.8%) than students (n = 6; 5.4%) (p = 0.010). Infection in childhood was probably the main HBV risk factor. The risk factors for HDV infection were age (p = 0.040), transfusion (p = 0.039), and a tendency for tattooing (p = 0.055) and absence of condom use (p = 0.049). HBV-E and HDV-1 were highly prevalent during both the FH outbreak and the 2010 screening project. For historical samples, due to storage conditions and despite several attempts, we could only obtain partial HDV amplification representing 25% of the full-length genome. The HDV-1 mid-eighties FH-strains did not form a specific clade and were affiliated to two different HDV-1 African subgenotypes, one of which also includes the 2010 HDV-1 strains. In the Central African Republic, these findings indicate a high prevalence of previous and current HBV-E and HDV-1 infections both in the mid-eighties fulminant hepatitis outbreak and among asymptomatic young adults in 2010, and reinforce the need for universal HBV vaccination and the prevention of HDV transmission among HBsAg-positive patients through blood or sexual routes.

First data on HIV-1 resistance mutations to antiretroviral drugs in Central African Republic.

In a background of high genomic HIV-1 variability with a predominance of CRF11_cpx and CRF22_01A1, we have studied the emergence of resistance mutations in isolates from Central African patients at failure of d4T-AZT/3TC/NVP-EFV plus two at failure of a PI-including regimen; the resistance mutations observed are those which are expected on HIV-1 subtype B.

Increasing HIV type 1 polymorphic diversity but no resistance to antiretroviral drugs in untreated patients from Central African Republic: a 2005 study.

As the HIV-1 pandemic becomes increasingly complex and as new countries acceed to antiretroviral drugs, the molecular characterization of HIV-1 strains circulating has important implications for vaccine research and for the efficacy of treatments. To follow the evolution of HIV-1 diversity in African countries, we have carried out a molecular analysis of HIV-1 strains collected from 150 HIV-1-positive pregnant women recruited in Bangui, Central African Republic (CAR). We have sequenced reverse transcriptase (RT) and protease (PROT) genes to (1) characterize the subtypes and CRFs, (2) describe the polymorphism of RT and PROT, particularly at the positions of drug resistance mutations in subtype B, and (3) observe potential drug resistance mutations and evaluate the prevalence of isolates bearing such mutations in this untreated population. The results showed that there is a very high and increasing diversity of HIV-1 strains circulating in CAR; out of 117 samples sequenced, we have observed 45 CRF11_cpx, 22 subtypes A1, 13 subtypes G, 7 subtypes CRF01_AE, 3 subtypes B, 3 subtypes CRF02_AG, 2 of each subtype F2 and CRF09_cpx, and one of each subtype D, J, C, H, CRF06_cpx, CRF13_cpx, and CRF19_cpx; the remaining 13 strains showed discordant genomic results suggesting multiple recombinations leading to mosaic viruses. The polymorphism of RT and PROT was high compared to subtype B, particularly at some positions that have been involved in antiretroviral resistance in subtype B, but we could not observe any major resistance mutation in this sample of untreated patients. The prevalence of drug resistance mutations in this population was therefore clearly under the WHO 5% threshold.