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.

Pediatric multi-drug resistant-tuberculosis and HIV co-infection in a resource-limited setting: a case report.

BACKGROUND: Tuberculosis remains a major cause of morbidity and mortality worldwide, especially in developing countries. The diagnosis and treatment of multi-drug resistant tuberculosis (MDR-TB) in children remain a major limitation in this setting, largely due to difficulties in isolating Mycobacterium tuberculosis from pediatric specimens, management with toxic second line drugs, and practically the inexistence of contact tracing. In 2016, the World Health Organization (WHO) recommended a standardized 9-month regimen for adults and children in zones which are highly endemic for the human immunodeficiency virus (HIV). Herein, we present a case of pediatric MDR-TB/HIV co-infection highlighting the difficulties in treatment and the importance of contact tracing. CASE PRESENTATION: A 6-year old male infant from the West Region of Cameroon infected with HIV who presented at a local health center with a 10 days history of productive cough associated with nocturnal fever and abdominal pains non responsive to broad spectrum antibiotics. A sputum sample analysis requested was smear positive for acid-fast bacilli, and he was initiated on quadritherapy for drug sensitive pulmonary tuberculosis. Since he was a household contact of the mother who was being managed in a referral hospital for MDR-TB at 1 month of treatment, and given his critical clinical situation, a gastric aspirate was repeated and sent for Xpert MTB/RIF to the Tuberculosis Reference Laboratory which was positive for a Rifampicin resistant strain of M. tuberculosis. The short 9 months regimen against MDR-TB was then initiated. During the course of his management, he developed minor side effects of the drugs which were managed symptomatically. CONCLUSION: Even though pediatric MDR-TB is difficult to confirm, it can be treated with favorable clinical outcomes using the short regimen recommended by the WHO. Experts involved in the control of tuberculosis over the national territory should consider adopting routine contact tracing for all cases of tuberculosis particularly amongst children.

Genetic Structure and Drug Susceptibility Patterns of Mycobacterium tuberculosis Complex Strains Responsible of Human Pulmonary Tuberculosis in the Major Rearing Region in Cameroon.

Background. Cameroon this last decade continues to present a low contribution of M. africanum and M. bovis in human tuberculosis (TB), while M. bovis was prevalent in cattle but all these pieces of information only concerned West and Center regions. Methods. We carried out the first study in Adamaoua, one of the most rearing regions of Cameroon, on the genetic structure and drug susceptibility of the MTBC strains isolated from newly diagnosed sputum smear-positive patients aged 15 years and above. For that purpose, spoligotyping, a modified 15 standard MIRU/VNTR loci typing, and the proportion method were used. Results. Four hundred and thirty-seven MTBC isolates were analyzed by spoligotyping. Of these, 423 were identified as M. tuberculosis, within the Cameroon family being dominant with 278 (65.7%) isolates; twelve (2.75%) isolates were classified as M. africanum and two as M. bovis. MIRU/VNTR typing of the most prevalent sublineage (SIT 61) suggested that this lineage is not a unique clone as thought earlier but could constitute a group of strains implicated to different pocket of TB transmission. Only M. tuberculosis sublineages were associated with antituberculosis drug resistance. Conclusion. These results showed the weak contribution of M. africanum and M. bovis to human active pulmonary tuberculosis in Cameroon even in the rearing region.

Shifts in Mycobacterial Populations and Emerging Drug-Resistance in West and Central Africa.

In this study, we retrospectively analysed a total of 605 clinical isolates from six West or Central African countries (Benin, Cameroon, Central African Republic, Guinea-Conakry, Niger and Senegal). Besides spoligotyping to assign isolates to ancient and modern mycobacterial lineages, we conducted phenotypic drug-susceptibility-testing for each isolate for the four first-line drugs. We showed that phylogenetically modern Mycobacterium tuberculosis strains are more likely associated with drug resistance than ancient strains and predict that the currently ongoing replacement of the endemic ancient by a modern mycobacterial population in West/Central Africa might result in increased drug resistance in the sub-region.

[Management of tuberculosis patients in the urban setting: health service delivery and health care-seeking behavior]. / Prise en charge des patients souffrant de la tuberculose en milieu urbain: offre de soins et parcours thérapeutique.

OBJECTIVES: This descriptive and prospective study was designed to determine the incidence of smear-positive pulmonary tuberculosis (PTB+) by health area (HA) in Douala, use of Diagnosis and Treatment Centres (DTCs) and the factors influencing the choice of DTC. METHODS: Over a one-year period, the residence of all PTB+ patients and the DTC at which they were treated were located by means of a GPS system and represented on a geo-referenced health map. Incidence of PTB+ per HA was calculated. Focus group discussions with TB patients were then held in seven of the nineteen DTCs chosen by convenience. RESULTS: The incidence of PTB+ is not randomly distributed between HAs, as the incidence is fivefold higher than the mean in some HAs. More than one half of patients (65%) were not treated in the DTC to which they were designated by the health system. Attendance in a DTC mostly depends on chance decisions based on previous experiences with a health care unit, recommendations from family members, friends or strangers, or the (sometimes erroneous) reference by health care personnel. References rarely follow the logic of the system. CONCLUSION: The provision of health care for TB in the city of Douala and health care-seeking behaviour of patients frequently do not correspond. Information and communication on TB care delivery could make the management of tuberculosis more efficient and more effective.

[Formative supervision: the experience of treatment units during cholera epidemic in Douala, Cameroon]. / Supervision formative: i'expérience des unités de traitement du choléra au cours de l'epidémie de Douala, Cameroun.

Formative supervision is a quality and performance tool based on evaluation and adult training techniques. The 2004 cholera outbreak in Douala (Cameroon) presented a critical problem in terms of quality of care; formative supervision emerged as the choice of instrument developed as a key response and solution. After a chronological qualitative description of how the supervision team and system were constituted, established and organized, the results are presented: strengthening infrastructure, equipment and organisation; improving the quality of care, hygiene, communication, and management. The system requires capacity building for sustainability in order to also be eventually extended to other health districts and other health sector activities, on the condition that the necessary resources can be mobilized.

Impact of resistance to anti-tuberculosis drugs on treatment outcome using World Health Organization standard regimens.

We compared treatment outcome in 410 patients with drug-susceptible tuberculosis (DS-TB) and 150 patients with drug-resistant tuberculosis (DR-TB) among 560 adult patients (> or = 15 years old) notified with smear-positive pulmonary tuberculosis between July 1997 and June 1998 in the West Province of Cameroon and treated with World Health Organization (WHO) standard regimens under field conditions. Information on treatment outcome was collected for all smear-positive TB patients having a positive culture with drug susceptibility tests performed for isoniazid, rifampicin, ethambutol and streptomycin. Treatment outcome was recorded as cured, completed treatment, failed, defaulted, died or transferred out, 332 of the 410 patients (81%) with DS-TB were cured, compared to 109/150 (72.7%) patients with DR-TB (odds ratio [OR] = 0.62, 95% confidence interval [CI] 0.40-0.99). Seven patients (1.7%) failed treatment in the DS-TB group vs. 9 (6.0%) in the DR-TB group (OR = 3.67, 95% CI 1.23-11.18). No significant difference was found in rates of death, default or transfer. Sputum smear conversion at the end of the intensive treatment phase was observed in 78.8% of the cases, drug resistance having no effect on the conversion rate. After adjusting for age, sex and resistance, the death rate was higher in patients also infected with human immunodeficiency virus (HIV). In TB cases with multidrug resistance, standard regimens result in unacceptably high failure rates (26.1%). For all other drug-resistant forms of TB, rifampicin-based short-course chemotherapy gave satisfactory results. The death toll in the West Province seems due to HIV co-infection rather than to TB alone. To prevent development of drug-resistance, the proportion of defaulters must be decreased and prevention and control strategies endorsed by the WHO and the International Union Against Tuberculosis and Lung Disease must be implemented nation-wide.