drug-resistant tuberculosis

In Uganda, various health system challenges impeded scale-up of DR-TB care in 2012; only three treatment initiation facilities existed, with only 41 of the estimated 1010 RR-TB/MDR-TB cases enrolled on treatment yet 300 were on the waiting list and there was no DR-TB treatment scale-up plan. To scale up care, the National TB and Leprosy Program (NTLP) with partners rolled out a DR-TB mixed model of care. In this paper, we share achievements and outcomes resulting from the implementation of this mixed Model of DR-TB care. Routine NTLP DR-TB program data on treatment initiation site, number of patients enrolled, their demographic characteristics, patient category, disease classification (based on disease site and human immunodeficiency virus (HIV) status), on co-trimoxazole preventive therapy (CPT) and antiretroviral therapy (ART) statuses, culture results, smear results and treatment outcomes (6, 12, and 24 months) from 2012 to 2017 RR-TB/MDR-TB cohorts were collected from all the 15 DR-TB treatment initiation sites. Over the period 2013–2015, the RR-TB/MDR-TB treatment success rate (TSR) was sustained between 70.1% and 74.1%, a performance that is well above the global TSR average rate of 50%. Additionally, the cure rate increased from 48.8% to 66.8% (P = 0.03). The Uganda DR-TB mixed model of care coupled with early application of continuous improvement approaches, enhanced cohort reviews and use of multi-disciplinary teams allowed for rapid DR-TB program expansion, rapid clearance of patient backlog, attainment of high cumulative enrollment and high treatment success rates.

To describe trends in diagnostic and treatment delays and estimate their effect on  rifampicin-resistant tuberculosis (RR-TB) mortality, we conducted a retrospective analysis of individual-level data including 748 (85.4%) of 876 patients diagnosed with RR-TB notified to the World Health Organization between 1 July 2005 and 31 December 2016 in Rwanda. Logistic regression was used to estimate the effect of diagnostic and therapeutic delays on RR-TB mortality. Between 2006 and 2016, the median diagnostic delay significantly decreased from 88 days to 1 day, and the therapeutic delay from 76 days to 3 days. Simultaneously, RR-TB mortality significantly decreased from 30.8% in 2006 to 6.9% in 2016.

Our objective was to assess the knowledge of health professionals on Xpert MTB/RIF assay and associated factors in detecting TB/TB drug resistance. An institution based cross–sectional study was conducted from April 4 to June 5, 2015, in Addis Ababa, that involved 209 healthcare providers working in TB clinics.The overall magnitude of knowledge of healthcare workers on Xpert was found to be low. Health workers above age 35 years and those who had read the guidelines on Xpert had greater knowledge of Xpert. Distribution of the national guidelines on Xpert and assigning experienced clinicians to TB DOTs clinics are recommended.

Ethambutol (EMB) resistance can evolve through a multistep process, and mutations in the ubiA (Rv3806c) gene appear to be responsible for high-level EMB resistance in Mycobacterium tuberculosis. We evaluated the prevalence of ubiA and embB (Rv3795) mutations in EMB-resistant strains originating from Africa and South Korea. No differences in embB mutation frequencies were observed between strains from both origins. However, ubiA mutations were present in 45.5% 6.5% of the African EMB-resistant isolates but in only 9.5% 1.5% of the South Korean EMB-resistant isolates. The ubiA mutations associated with EMB resistance were localized to regions encoding the transmembrane domains of the protein, whereas the embB mutations were localized to regions encoding the extramembrane domains. Larger studies are needed to investigate the causes of increased ubiA mutations as a pathway to high-level EMB resistance in African countries, such as extended EMB usage during tuberculosis treatment.

The objective of this study was to assess the prevalence, profile and outcome of adverse events (AEs) associated with treatment of drug-resistant tuberculosis (DR-TB) and explore possible influences of HIV disease on the occurrence of adverse events. Data were collected from treatment records of all patients treated for DR-TB at the study facility between January 2008 and February 2010. A total of 141 adverse events of varying severity were experienced in 90% (53/59) of patients.The TB/HIV co-infection rate was 53%. The prevalence of gastrointestinal tract adverse events was 64%, tinnitus 45%, joint pain 28% and decreased hearing 25%. Abdominal pains, rash, nausea, decreased hearing and joint pain were more common in HIV infected than in HIV uninfected patients.

To improve tuberculosis (TB) diagnosis, many national TB programmes have committed to deploying Xpert® MTB/RIF. Implementation of this relatively new technology has suffered from a lack of comprehensive technical assistance, however, including the formulation of policies and plans to address operational issues. While providing technical assistance, we observed numerous operational challenges in the implementation and scale-up of Xpert in five sub-Saharan African countries: low coverage, poor laboratory infrastructure, limited access, poor linkages to treatment, inadequate data on outcomes, problems with specimen transport, diagnostic algorithms that are not aligned with updated World Health Organization recommendations on target patient groups and financing challenges. We recommend better country preparedness and training, laboratory information and quality systems, supply management and referral mechanisms.

The aim of this study was to assess the prevalence of MDR-TB and associated risk factors in West Armachiho and Metema districts of North Gondar. A cross-sectional study was conducted between February 1 and June 25, 2014. A total of 124 consecutive smear-positive pulmonary TB patients were included in the study. Socio-demographic and possible risk factor data were collected using a semi-structured questionnaire. Drug susceptibility testing was first performed for rifampicin using GeneXpert MTB/RIF. For those rifampicin resistant strains, drug susceptibility testing was performed for both isoniazid and rifampicin to identify MDR-TB. Of 124 smear-positive pulmonary TB patients, 117 (94.4 %) were susceptible to rifampicin, while 7 (5.7 %) were confirmed to be resistant to rifampicin and isoniazid. History of previous treatment was significantly associated with MDR-TB. Maximizing early case detection and treatment, strengthening TB infection control activities and proper implementation of DOTS are recommended to reduce the burden of MDR-TB.

 In 2013 the Global Drug Facility reduced the price of the second-line drugs it supplies for multidrug-resistant tuberculosis (MDR TB): the overall cost of the longest and most expensive treatment regimen for a patient decreased by 26%, from US$7,890 in 2011 to US$5,822 in 2013. The price of treatment for MDR TB was reduced by consolidating orders to achieve large purchase volumes, by international, competitive bidding and by the existence of donor-funded medicine stockpiles. The rise in the number of suppliers of internationally quality-assured drugs was also important. The savings achieved from lower drug costs could be used to increase the number of patients on high-quality treatment.

We set out to evaluate the variation in prevalence of drug resistant tuberculosis (DR-TB) and its determinants across sub-Saharan African (SSA) countries--excluding South Africa--among new and previously treated TB patients. A search of PubMed, EMBASE, Cochrane and bibliographies of DR-TB studies yielded 726 studies published between 2003 and 2013, of which 27 articles fulfilled the inclusion criteria. Studies reported drug susceptibility testing results for a total of 13,465 new and 1,776 previously treated TB patients. The pooled estimate of any DR-TB prevalence among the new cases was 12.6%, while for MDR-TB this was 1.5%. Among previously treated patients, these were 27.2% and 10.3%, respectively. DR-TB (any and MDR-TB) did not vary significantly with respect to study characteristics. The reported prevalence of DR-TB in SSA is low compared to WHO estimates. MDR-TB in this region does not seem to be driven by the high HIV prevalence rates.

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