First-line tuberculosis treatment with double-dose rifampicin is well tolerated.

OBJECTIVE: To compare the occurrence of unfavourable treatment and safety outcomes of double-dose rifampicin (RMP; 20 mg/kg/d, intervention) with standard dose (10 mg/kg/d, control) in a first-line tuberculosis (TB) treatment regimen for smear-positive TB patients in Bangladesh.DESIGN: This was a randomised clinical trial. The primary efficacy and safety endpoints were the occurrence of an unfavourable treatment outcome (death, failure, relapse or loss to follow-up) and the occurrence of any serious drug-related adverse event (SAE).RESULTS: In primary efficacy analysis, among 343 control and 347 intervention patients, respectively 15.5% and 11.8% had an unfavourable outcome. In safety analysis, among 349 intervention and 352 control patients, respectively 4.3% and 2.6% experienced an SAE. These differences were not significant. There was a significantly lower occurrence of SAEs, explained by a lower occurrence of hepatic toxicity, in a RMP double-dosed but erroneously HZE (isoniazid+pyrazinamide+ethambutol) under-dosed subgroup.CONCLUSIONS: Our findings show that there is no statistically significant difference in terms of efficacy and safety between standard and double-dose RMP. An accidental finding (related to dosage levels of the standard regimen) suggests that high-dose RMP is potentially a lesser cause of hepatotoxicity. Larger trials with more power, or trials with at least a triple-dose might be needed to clearly see the effect of high-dose RMP on unfavourable outcomes.

Drug resistance profiles of new- and previously treated patients with pulmonary tuberculosis in Ibadan, Nigeria.

BACKGROUND: Information on TB drug resistance profiles and its' associated risk factors are scarce in Nigeria despite the large burden of disease in the country. The study was designed to report drug resistance profiles of new- and previously treated patients with pulmonary tuberculosis (TB) in Ibadan, Nigeria. METHOD: Sputum from consenting pulmonary TB patients were collected and cultured for Mycobacterium tuberculosis (Mtb) at the TB laboratory of the University College Hospital, Ibadan, Nigeria using standard method. Mtb were stored and sent for drug susceptibility testing against first and second-line anti-TB drugs at the MRC Unit, The Gambia and at the Institute of Tropical Medicine, Antwerp, Belgium using BACTEC MGIT 960 and proportion method on solid medium respectively. RESULTS: Of 238 Mtb collected, 124 (52.1%) were viable, 102 (59.65%) non-viable while 12 (7.02%) were contaminated. About half (58.87%) of the Mtb were from previously treated patients, 40 (32.26%) were from new patients while treatment history of 1.1 (8.87%) were unknown. Forty-seven (37.90%) of the 124 Mtb. tested were multidrug resistant (MDR) out of which, 40 (85.10%) were from previously treated patients.. HIV prevalence was 8.69%. Of the 17 MDR-TB from previously treated cases tested for second-line drugs, four (23.53%) were resistant to fluoroquinolones or injectable agents, 13 (76.47%) were susceptible while none was resistant to both of these classes of drugs. CONCLUSION: MDR-TB in Ibadan already demonstrates resistance to second line anti-TB drugs hence management of MDR-TB patients should be strengthened to prevent emergence of extensively drug-resistant TB (XDR-TB).

Effect of increased ART-CPT uptake on tuberculosis outcomes and associated factors, Burundi, 2009-2013.

We retrospectively examined 3579 records of human immunodeficiency virus infected tuberculosis (TB) patients diagnosed from January 2009 to June 2013 in 55 TB treatment facilities in Burundi, to demonstrate whether improvement of combined cotrimoxazole preventive therapy and antiretroviral therapy (ART) uptake was accompanied by improvement of treatment outcomes, and to describe associated factors. Treatment success rates increased from 71% to 80% (P < 0.001). While loss to follow-up and transfer-out rates declined significantly, death rates decreased modestly, and remained high, at 14%. ART uptake was worse in suburban areas and private for-profit institutions. World Health Organization targets could be achieved if peripheral health facilities were prioritised.

Une étude rétrospective conduite de janvier 2009 à juin 2013 au Burundi chez 3579 patients co-infectées par la tuberculose (TB) et le virus de l'immunodéficience humaine dans 55 centres de diagnostic et de traitement de la TB, décrit l'évolution des résultats de traitement antirétroviral (ART) et cotrimoxazole et apprécie les facteurs liés à l'ART. La proportion des succès au traitement a augmenté de 71% à 80% (P < 0,001). Tandis que les taux de perdus de vue et de transferts ont baissé significativement, celui des décès n'a baissé que modestement, tout en restant élevée, à 14%. La couverture en ART est plus faible dans les centres de santé périphériques et dans ceux relevant du privé non lucratif. Les objectifs de l'Organisation Mondiale de la Santé pourraient être atteints si les districts sanitaires ruraux étaient inclus dans la fourniture des soins.

En el presente estudio se analizaron 3579 registros de pacientes aquejados de coinfección por el virus de la inmunodeficiencia humana (VIH) y la tuberculosis (TB) en Burundi de enero del 2009 a junio del 2013, provenientes de 55 establecimientos de tratamiento de la TB, con el objeto de investigar si al aumentar la aceptación del tratamiento preventivo con cotrimoxazol en asociación con el tratamiento antirretrovírico (ART) se mejoraban los desenlaces terapéuticos y también se describieron los factores que se asociaban con esta situación. Las tasas de éxito terapéutico aumentaron de un 71% a un 80% (P < 0,001). Aunque las tasas de pérdida durante el seguimiento y de remisión a otros establecimientos disminuyeron de manera significativa, la disminución de las tasas de mortalidad fue leve y permanecieron en un nivel alto de 14%. La aceptación del ART fue más deficiente en las zonas suburbanas y en los establecimientos privados con ánimo de lucro. Sería posible cumplir con las metas de la Organización Mundial de la Salud si se da prioridad a los establecimientos sanitarios periféricos.

Inadequacy of the current WHO re-treatment regimen in a central Siberian prison: treatment failure and MDR-TB.

Multidrug-resistant tuberculosis (MDR-TB) threatens the progress of global control efforts. Prisons represent a high risk setting for development and transmission of MDR-TB. In a Siberian TB referral prison (Kemerovo region), the treatment failure rate is 35% (June 1996-March 1997), despite implementation of a strict DOTS program and use of the World Health Organization Category 2 re-treatment regimen for all new cases. Among 164 patients (December 1997-March 1998), initial resistance to isoniazid and rifampin is 22.6%. Such a rate is a warning call to reconsider prison control strategies, and importantly, to address the treatment regimens necessary to combat an institutional epidemic of MDR-TB.