Multidrug-Resistant Tuberculosis in Côte d'Ivoire from 1995 to 2016: Results of National Surveys.

SETTING: Tuberculosis (TB) drug resistance survey was conducted in 2016-2017 to estimate the burden of drug-resistant TB in Côte d'Ivoire. DESIGN: A cross-sectional cluster-based survey was conducted. All eligible smear positive patients were interviewed using a structured questionnaire to collect clinical and sociodemographic information and tested by the Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) assay. If resistant to rifampicin, solid and liquid cultures were performed. Phenotypic drug susceptibility testing (DST) was conducted in liquid medium for rifampicin, isoniazid, ethambutol, streptomycin, ofloxacin, and amikacin. RESULTS: Of the 1105 sputum smear positive patients enrolled, 995 new and 100 previously treated patients were positive for Mycobacterium tuberculosis complex by Xpert. Proportion of patients with rifampicin resistance was 4.6% (95% CI: 2.4-6.7) and 22% (95% CI: 13.7-30.3), respectively, for new and previously treated patients. Second-line DST results were available for most rifampicin-resistant patients. None were resistant to amikacin, only two were ofloxacin-resistant. Apart from the antecedent of previously treatment for TB, no other risk factors for rifampicin resistance were detected. CONCLUSION: Prevalence of rifampicin resistance among TB patients in Côte d'Ivoire is higher than that in other countries in the region. Surveillance of drug resistance, through an expanded GeneXpert network, and programmatic management of drug-resistant TB (PMDT) must be strengthened in Côte d'Ivoire.

Prevalence of pulmonary tuberculosis among prison inmates: A cross-sectional survey at the Correctional and Detention Facility of Abidjan, Côte d'Ivoire.

BACKGROUND: In Côte d'Ivoire, a TB prison program has been developed since 1999. This program includes offering TB screening to prisoners who show up with TB symptoms at the infirmary. Our objective was to estimate the prevalence of pulmonary TB among inmates at the Correctional and Detention Facility of Abidjan, the largest prison of Côte d'Ivoire, 16 years after this TB program was implemented. METHODS: Between March and September 2015, inmates, were screened for pulmonary TB using systematic direct smear microscopy, culture and chest X-ray. All participants were also proposed HIV testing. TB was defined as either confirmed (positive culture), probable (positive microscopy and/or chest X-ray findings suggestive of TB) or possible (signs or symptoms suggestive of TB, no X-Ray or microbiological evidence). Factors associated with confirmed tuberculosis were analysed using multivariable logistic regression. RESULTS: Among the 943 inmates screened, 88 (9.3%) met the TB case definition, including 19 (2.0%) with confirmed TB, 40 (4.2%) with probable TB and 29 (3.1%) with possible TB. Of the 19 isolated TB strains, 10 (53%) were TB drug resistant, including 7 (37%) with multi-resistance. Of the 10 patients with TB resistant strain, only one had a past history of TB treatment. HIV prevalence was 3.1% overall, and 9.6%among TB cases. Factors associated with confirmed TB were age ≥30 years (Odds Ratio 3.8; 95% CI 1.1-13.3), prolonged cough (Odds Ratio 3.6; 95% CI 1.3-9.5) and fever (Odds Ratio 2.7; 95% CI 1.0-7.5). CONCLUSION: In the country largest prison, pulmonary TB is still 10 (confirmed) to 44 times (confirmed, probable or possible) as frequent as in the Côte d'Ivoire general population, despite a long-time running symptom-based program of TB detection. Decreasing TB prevalence and limiting the risk of MDR may require the implementation of annual in-cell TB screening campaigns that systematically target all prison inmates.

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa.

BACKGROUND: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. METHODS: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. RESULTS: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. CONCLUSIONS: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.).

Incidence of serious morbidity in HIV-infected adults on antiretroviral therapy in a West African care centre, 2003-2008.

BACKGROUND: In resource-limited settings, scaling-up antiretroviral treatment (ART) has required the involvement of decentralized health facilities with limited equipment. We estimated the incidence of serious morbidity among HIV-infected adults receiving ART in one of these HIV routine care center in sub-Saharan Africa. METHODS: We conducted a prospective study at the Centre Medical de Suivi des Donneurs de Sang (CMSDS), which is affiliated with the National Centre for Blood Transfusion in Abidjan, Côte d'Ivoire. Adult patients infected with HIV-1 or HIV-1/HIV-2 who initiated ART between January 2003 and December 2008 were eligible for the study. Standardized clinical data were collected at each visit. Serious morbidity was defined as a new episode of malaria, WHO stage 3-4 event, ANRS grade 3-4 adverse event, or any event leading to death or to hospitalization. RESULTS: 1008 adults, 67% women, with a median age of 35 years, and a median pre-ART CD4 count of 186/mm3 started ART and were followed for a median of 17.3 months. The overall incidences of loss to follow-up, death, and attrition were 6.2/100 person-years (PY) [95% CI 5.1-7.2], 2.3/100 PY [95% CI 1.6-2.9], and 8.1/100 PY [95% CI 7.0-9.4], respectively. The incidence of first serious event was 11.5/100 PY overall, 15.9/100 PY within the first year and 8.3/100 PY thereafter. The most frequently documented specific diagnoses were malaria, tuberculosis, bacterial septicemia and bacterial pneumonia. CONCLUSION: Among HIV-infected adults followed in routine conditions in a West African primary care clinic, we recorded a high incidence of serious morbidity during the first year on ART. Providing care centers with diagnostic tools and standardizing data collection are necessary steps to improve the quality of care in primary care facilities in sub-Saharan Africa.

High prevalence of shared international type 53 among Mycobacterium tuberculosis complex strains in retreated patients from Côte d'Ivoire.

BACKGROUND: Genotyping methods are useful tools to provide information on tuberculosis epidemic. They can allow a better response from health authorities and the implementation of measures for tuberculosis control. This study aimed to identify the main lineages and clades of Mycobacterium tuberculosis complex strains circulating in Côte d'Ivoire. METHODS/MAIN FINDINGS: Strains isolated from sputum samples of patients ongoing retreatment from all the country were characterized by spoligotyping and by MIRU-VNTR. Profiles obtained by spoligotyping were first compared to the SITVIT/SpolDB4 database for family assignment. Of 194 strains analysed, 146 (75.3%) belonged to the T lineage. The most predominant spoligotype was the shared international type 53 with 135 strains (69.6%). In contrast with neighbouring countries, LAM (11 strains, 5.7%) and H (9 strains 4.6%) lineages were slightly represented. Only 3 Beijing strains (1.5%) and 4 strains of Mycobacterium africanum (2%) were found. Analysis of the results obtained with MIRU-VNTR revealed also a high level of clustering. CONCLUSION/SIGNIFICANCE: The population of Mycobacterium tuberculosis complex strains among retreatment cases in Côte d'Ivoire exhibits a low diversity, allowing to assume recent transmission and locally based infection.

AIDS and non-AIDS morbidity and mortality across the spectrum of CD4 cell counts in HIV-infected adults before starting antiretroviral therapy in Cote d'Ivoire.

BACKGROUND: In Western Europe, North America, and Australia, large cohort collaborations have been able to estimate the short-term CD4 cell count-specific risk of AIDS or death in untreated human immunodeficiency virus (HIV)-infected adults with high CD4 cell counts. In sub-Saharan Africa, these CD4 cell count-specific estimates are scarce. METHODS: From 1996 through 2006, we followed up 2 research cohorts of HIV-infected adults in Côte d'Ivoire. This included follow-up off antiretroviral therapy (ART) across the entire spectrum of CD4 cell counts before the ART era, and only in patients with CD4 cell counts >200 cells/µL once ART became available. Data were censored at ART initiation. We modeled the CD4 cell count decrease using an adjusted linear mixed model. CD4 cell count-specific rates of events were obtained by dividing the number of first events occurring in a given CD4 cell count stratum by the time spent in that stratum. RESULTS: Eight hundred sixty patients were followed off ART over 2789 person-years (PY). In the ≥650, 500-649, 350-499, 200-349, 100-199, 50-99, and 0-49 cells/µL CD4 cell count strata, the rates of AIDS or death were 0.9, 1.7, 3.7, 10.4, 30.9, 60.8, and 99.9 events per 100 PY, respectively. In patients with CD4 cell counts ≥200 CD4 cells/µL, the most frequent AIDS-defining disease was tuberculosis (decreasing from 4.0 to 0.6 events per 100 PY for 200-349 and ≥650 cells/µL, respectively), and the most frequent HIV non-AIDS severe diseases were visceral bacterial diseases (decreasing from 9.1 to 3.6 events per 100 PY). CONCLUSIONS: Rates of AIDS or death, tuberculosis, and invasive bacterial diseases are substantial in patients with CD4 cell counts ≥200 cells/µL. Tuberculosis and bacterial diseases should be the most important outcomes in future trials of early ART in sub-Saharan Africa.

Incidence and determinants of mortality and morbidity following early antiretroviral therapy initiation in HIV-infected adults in West Africa.

OBJECTIVE: To estimate the incidence and risk factors of mortality and severe morbidity during the first months following antiretroviral therapy (ART) initiation in West African adults. METHODS: A cohort study in Abidjan in which 792 adults started ART with a median CD4 cell count of 252 cells/mul and were followed for a median of 8 months. Severe morbidity was defined as all World Health Organization stage 3 or 4-defining morbidity events other than oral candidiasis. RESULTS: In patients with pre-ART CD4 cell count < 200, at 200-350 and > 350 cells/mul, incidence of mortality was 5.0 [95% confidence interval (CI), 2.6-8.7], 1.7 (95% CI, 0.6-3.8) and 0.0 (95% CI, 0.0-3.4]/100 person-years, and incidence of severe morbidity was 13.3 (95% CI, 9.0-19.1), 9.5 (95% CI, 6.2-12.9) and 7.9 (95% CI, 3.4-15.5)/100 person-years, respectively. The most frequent diseases were invasive bacterial diseases (32/65 episodes, 49%) and tuberculosis (25/65 episodes, 38%). Both diseases followed the same curve of decreasing incidence over time. Patients who experienced severe morbidity had higher risks of mortality, virological failure and immunological failure. Other independent risk factors for mortality and/or severe morbidity were: at baseline, high viral load, advanced clinical stage, past history of tuberculosis, low BMI, low haemoglobin and low CD4 cell count; during follow-up: low CD4 cell count and persistently detectable viral load. CONCLUSION: These data give new arguments to reinforce the hypothesis that, in this region, ART should be started before the CD4 cell count drops below 350 cells/mul. Further studies should assess whether patients with low BMI, low haemoglobin, high viral load or past history of tuberculosis should start ART earlier.

Pattern of bacterial diseases in a cohort of HIV-1 infected adults receiving cotrimoxazole prophylaxis in Abidjan, Côte d'Ivoire.

BACKGROUND: WHO/UNAIDS recommended that cotrimoxazole should be prescribed in Africa in HIV-infected adults with CD4 cell counts < 500 x 10 /l, while closely monitoring bacterial diseases in as many settings as possible. METHODS: Prospective cohort study, describing bacterial morbidity in adults receiving cotrimoxazole prophylaxis (960 mg daily) between April 1996 and June 2000 in Abidjan, Côte d'Ivoire. RESULTS: Four-hundred and forty-eight adults (median baseline CD4 cell count 251 x 10 /l) were followed for a median time of 26 months. The rates of overall bacterial diseases and of serious bacterial diseases with hospital admission were 36.8/100 person-years (PY) and 11.3/100 PY, respectively. Bacterial diseases were the first causes of hospital admissions, followed by non-specific enteritis (10.2/100 PY), acute unexplained fever (8.4/100 PY), and tuberculosis (3.6/100 PY). Among serious bacterial diseases, the most frequent were enteritis (3.0/100 PY), invasive urogenital infections (2.5/100 PY), pneumonia (2.3/100 PY), bacteraemia with no focus (2.0/100 PY), upper respiratory tract infections (1.6/100 PY) and cutaneous infections (0.6/100 PY). Compared with patients with baseline CD4+ cell counts >or= 200 x 10 /l, other patients had an adjusted hazard ratio of serious bacterial diseases of 3.05 (95% confidence interval, 2.00-4.67; < 0.001). Seventy-five bacterial strains were isolated during serious episodes including 29 non-, 14, 12 spp, and 12. DISCUSSION: Though with a medium-term rate half that of the short-term rate estimated under placebo before 1998 (26.1/100 PY), serious bacterial morbidity remains the first cause of hospital admission in adults receiving cotrimoxazole in this setting.

Causes and empirical treatment of fever in HIV-infected adult outpatients, Abidjan, Côte d'Ivoire.

OBJECTIVES: In Abidjan, HIV prevalence has been estimated at 20% in outpatients attending community clinics. Documenting causes of fever in HIV-infected adult outpatients may help to improve care in these centres with limited facilities. DESIGN: Prospective study. METHODS: We describe all diagnoses and treatments made during febrile episodes in HIV-infected adults participating in the ANRS 059 trial and followed up in a dedicated outpatient centre. RESULTS: Causes of fever could be identified in half of the 269 febrile episodes. Bacterial diseases were the leading identified cause of fever in all CD4 cell count strata (53, 56 and 43% of identified causes in episodes with CD4 count < 200 x 106/l, 200-499 x 106/l, and >or= 500 x 106/l, respectively), followed by malaria (5, 22, and 38%, respectively). Among febrile bacterial diseases, respiratory tract infections and enteritis accounted for 62% of organ involvement, and Streptococcus pneumoniae and non-typhi Salmonella represented 69% of isolated bacterial strains. In these bacterial episodes, an early empirical antibacterial treatment was associated with shorter duration of hospitalization and fever. In the 19 episodes leading to death (7%), the two leading diagnoses were atypical mycobacteriosis (26%) and acute unexplained fever (21%). Death was associated with the absence of antimalarial treatment in the group of acute unexplained fevers. CONCLUSIONS: African HIV treatment guidelines should take into account the predominant role of bacterial infections and malaria in HIV-infected adult outpatients. Reports from other African settings would be useful to compare experiences in algorithms of empirical early antibacterial and antimalarial treatments.