Bedaquiline and delamanid result in low rates of unfavourable outcomes among TB patients in Eswatini.

SETTING: Since 2015, Eswatini has been scaling up bedaquiline (BDQ) and delamanid (DLM) based drug-resistant TB treatment regimens under programmatic conditions.OBJECTIVE: Identification of factors associated with treatment outcomes in patients receiving BDQ and/or DLM either as a new treatment initiation or drug substitution.DESIGN: This is a retrospective cohort study of patients receiving BDQ and/or DLM in Eswatini between March 2015 and October 2018. We describe factors associated with unfavourable treatment outcomes (death, lost to follow-up, treatment failure and amplification of resistance) and culture conversion using multivariable flexible parametric survival and competing-risks regression analyses.RESULTS: Of 352 patients receiving BDQ and/or DLM, 7.8% and 21.2% had an unfavourable treatment outcome at 6 and 24 months, respectively. Predictors were age ≥ 60 years (adjusted hazard ratio aHR 4.49, 95%CI 1.61-12.57) vs. age 20-39 years, and a treatment regimen combining both drugs (aHR 4.49, 95%CI 1.61-12.57) vs. BDQ only. The probability of culture conversion was increased for two health facilities and patients with a poly resistance profile (adjusted sub-hazard ratio 2.01, 95%CI 1.13-3.59) vs. multidrug resistance.CONCLUSION: Single use of BDQ or DLM was associated with low rates of unfavourable outcomes, suggesting that these medications may be effectively adopted at scale under routine programmatic conditions. Combined use of BDQ and DLM was a risk factor for unfavourable outcomes and should prompt for collection of more data on the combined use of these medications.

Operational aspects of bedaquiline implementation in Swaziland: report from the field.

Bedaquiline (BDQ) has been recommended by the World Health Organization for the treatment of multi-drug-resistant tuberculosis (MDR-TB) since 2013, but experience using the drug in high-burden, lower-income countries is limited and case studies are needed. Swaziland started using BDQ under national TB programme conditions in 2015 in four pilot sites. As of 1 December 2016, 93 patients had been initiated on BDQ, i.e., 19% of MDR-TB patients treated in the country. Swaziland has developed a systematic and efficient model for BDQ introduction in collaboration with several partners. This model is also being used to introduce other innovations and can serve as an example for other countries facing similar challenges.

La bédaquiline (BDQ) a été recommandée par l'Organisation Mondiale de la Santé pour le traitement de la tuberculose multirésistante (TB-MDR) depuis 2013, mais l'expérience de son utilisation dans des pays à faible revenu et durement touchés est limitée et des études de cas sont requises. Le Swaziland a commencé à utiliser la BDQ dans des conditions de programme national TB en 2015 dans quatre sites pilotes. Au 1er décembre 2016, 93 patients avaient été mis sous BDQ, c'est-à-dire 19% des patients TB-MDR traités dans le pays. Le Swaziland a élaboré un modèle systématique et efficace d'introduction de la BDQ en collaboration avec plusieurs partenaires. Ce modèle est également utilisé pour introduire d'autres innovations et peut servir d'exemple à d'autres pays confrontés à des défis similaires.

La Organización Mundial de la Salud recomienda desde el 2013 la bedaquilina (BDQ) en el tratamiento de la tuberculosis multirresistente (TB-MDR), pero la experiencia con su utilización en los países con alta carga de morbilidad es limitada y se precisan estudios de casos. En Swazilandia, se comenzó a utilizar la BDQ en el contexto del programa nacional contra la TB en cuatro centros piloto en el 2015. Al 1° de diciembre del 2016, 93 pacientes habían iniciado el tratamiento con BDQ, es decir, el 19% de los casos de TB-MDR tratados en el país. En Swazilandia se ha elaborado un modelo sistemático y eficiente de introducción de este medicamento en colaboración con diversos asociados. El modelo se utiliza también con el propósito de aplicar otras medidas innovadoras y puede servir como ejemplo a los países que afrontan dificultades semejantes.

Examples of bedaquiline introduction for the management of multidrug-resistant tuberculosis in five countries.

BACKGROUND: For the first time in almost 50 years, there are new drugs available for the treatment of tuberculosis (TB), including bedaquiline (BDQ) and delamanid (DLM). The rate of introduction, however, has not kept pace with patient needs. It is estimated that as many as 23% of multidrug-resistant TB (MDR-TB) patients have an indication for receiving BDQ. As this is the first time the MDR-TB community is introducing new medications, it is important to understand how implementation can be developed in a variety of settings. METHODS: A qualitative assessment of country TB programs in which more than 5% of MDR-TB patients were started on BDQ under program conditions. RESULTS: National TB programs in Belarus, France, Georgia, South Africa, and Swaziland all started sizeable cohorts of patients on BDQ in 2015. Common factors observed in these programs included experience with compassionate use/expanded access, support from implementing partners, and adequate national or donor-supported budgets. Barriers to introduction included restriction of BDQ to the in-patient setting, lack of access to companion drugs, and the development of systems for pharmacovigilance. CONCLUSION: The five countries in this paper are examples of the introduction of new therapeutic options for the treatment of TB.

Baseline epidemiological studies for a hepatitis B vaccine trial in Kangwane.

Hepatitis B markers were determined by radioimmunoassay of serum samples from 1 495 Black subjects representative of the resident population of Kangwane, a rural area with a high incidence of chronic liver disease and hepatocellular carcinoma. Pregnant women formed an important part of the study group, since it was intended to assess the frequency of perinatal transmission and the passive immunity of their infants, two factors which would markedly influence an infant immunization programme. A high overall marker positivity rate was found, indicating that hepatitis B is endemic. The hepatitis B surface antigen (HBsAg) carrier rate was 14,6% in adult males and 4,6% in adult females, while 82.6% of adult males and 69,4% of adult females were positive for at least one marker, indicating that infection had been present at some stage. Of infants under 1 year of age 34,5% were positive for antibodies to HBsAg (anti-HBs), compared with 9,3% at 13-24 months, which indicates that transplacental transfer of anti-HBs is frequent. Other markers were acquired even in the 1st year of life, with the sharpest increase at 3-11 years. Perinatal transmission was not common, however, and horizontal transmission during early childhood seemed to play an important role. It was concluded that the risk and frequency of infection justified a vaccine trial in this population and that the target group for vaccination should be infants under 1 year of age.