• Accuracy of molecular drug susceptibility testing amongst tuberculosis patients in Karakalpakstan, Uzbekistan.

      Gil, Horacio; Margaryan, Hasmik; Azamat, Ismailov; Ziba, Bekturdieva; Bayram, Halmuratov; Nazirov, Pirimqul; Gomez, Diana; Singh, Jatinder; Zayniddin, Sayfutdinov; Parpieva, Nargiza; et al. (2021-01-06)
      Objectives In this retrospective study, we evaluated the diagnostic accuracy of molecular tests (MT) for the detection of DR‐TB, compared to the gold standard liquid‐based Drug Susceptibility Testing (DST) in Karakalpakstan. Methods A total of 6,670 specimens received in the Republican TB No 1 Hospital Laboratory of Karakalpakstan between January and July 2017 from new and retreatment patients were analyzed. Samples were tested using Xpert MTB/RIF and line probe assays (LPA) for the detection of mutations associated with resistance. The sensitivity and specificity of MTs were calculated relative to results based on DST. Results The accuracy of MT for detection of rifampicin resistance was high, with sensitivity and specificity over 98%. However, we observed reduced sensitivity of LPA for detection of resistance; 86% for isoniazid (95%CI 82‐90%), 86% for fluoroquinolones (95%CI 68‐96%), 70% for capreomycin (95%CI 46‐88%) and 23% for kanamycin (95%CI 13‐35%). Conclusions We show that MTs are a useful tool for rapid and safe diagnosis of DR‐TB, however, clinicians should be aware of their limitations. Although detection of rifampicin resistance was highly accurate, our data suggests that resistance mutations circulating in the Republic of Karakalpakstan for other drugs were not detected by the methods used here. This merits further investigation.
    • Cost Per Patient of Treatment for Rifampicin-Resistant Tuberculosis in a Community-Based Programme in Khayelitsha, South Africa

      Cox, H; Ramma, L; Wilkinson, L; Azevedo, V; Sinanovic, E (Wiley-Blackwell, 2015-10)
      The high cost of rifampicin-resistant tuberculosis (RR-TB) treatment hinders treatment access. South Africa has a high RR-TB burden, and national policy outlines decentralisation to improve access and reduce costs. We analysed health system costs associated with RR-TB treatment by drug resistance profile and treatment outcome in a decentralised programme.
    • Diagnosis of pulmonary tuberculosis in a pastoralist population in Ethiopia: are three sputum specimens needed?

      Khogali, M; Tayler-Smith, K; Zachariah, R; Gbane, M; Zimble, S; Weyeyso, T; Harries, A D; Medecins sans Frontieres - Medical Department (Operational research Unit/Operations), Operational centre Brussels, MSF, Luxembourg, Luxembourg. Mohammed.Khogali@gmail.com (Blackwell Publishing Ltd, 2013-05-18)
      To assess the number of sputum specimens necessary for a reliable diagnosis of pulmonary tuberculosis (PTB) in a pastoralist population in Ethiopia.
    • 'I cry every day': experiences of patients co-infected with HIV and multidrug-resistant tuberculosis.

      Isaakidis, P; Rangan, S; Pradhan, A; Ladomirska, J; Reid, T; Kielmann, K; Médecins Sans Frontières, Mumbai, India. (2013-09-15)
      To understand patients' challenges in adhering to treatment for MDR-TB/HIV co-infection within the context of their life circumstances and access to care and support.
    • Integrating tuberculosis and HIV care in the primary care setting in South Africa.

      Coetzee, D; Hilderbrand, K; Goemaere, E; Matthys, F; Boelaert, M; Infectious Disease Research Unit, School of Public Health and Family Medicine, University of Cape Town, Observatory, South Africa. dcoetzee@cormack.uct.ac.za (2004-06)
      BACKGROUND: In many countries including South Africa, the increasing human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics have impacted significantly on already weakened public health services. This paper reviews the scope, process and performance of the HIV and TB services in a primary care setting where antiretroviral therapy is provided, in Khayelitsha, South Africa, in order to assess whether there is a need for some form of integration. METHODS: The scope and process of both services were assessed through observations of the service and individual and group interviews with key persons. The performance was assessed by examining the 2001-2002 reports from the health information system and clinical data. RESULTS: The TB service is programme oriented to the attainment of an 85% cure rate amongst smear-positive patients while the HIV service has a more holistic approach to the patient with HIV. The TB service is part of a well-established programme that is highly standardized. The HIV service is in the pilot phase. There is a heavy load at both services and there is large degree of cross-referral between the two services. There are lessons that can be learnt from each service. There is an overlap of activities, duplication of services and under-utilization of staff. There are missed opportunities for TB and HIV prevention, diagnosis and management. CONCLUSIONS: The study suggests that there may be benefits to integrating HIV and TB services. Constraints to this process are discussed.
    • The role of targeted viral load testing in diagnosing virological failure in children on antiretroviral therapy with immunological failure.

      Davies, M-A; Boulle, A; Technau, K; Eley, B; Moultrie, H; Rabie, H; Garone, D; Giddy, J; Wood, R; Egger, M; et al. (2012-09-14)
      Objectives  To determine the improvement in positive predictive value of immunological failure criteria for identifying virological failure in HIV-infected children on antiretroviral therapy (ART) when a single targeted viral load measurement is performed in children identified as having immunological failure. Methods  Analysis of data from children (<16 years at ART initiation) at South African ART sites at which CD4 count/per cent and HIV-RNA monitoring are performed 6-monthly. Immunological failure was defined according to both WHO 2010 and United States Department of Health and Human Services (DHHS) 2008 criteria. Confirmed virological failure was defined as HIV-RNA >5000 copies/ml on two consecutive occasions <365 days apart in a child on ART for ≥18 months. Results  Among 2798 children on ART for ≥18 months [median (IQR) age 50 (21-84) months at ART initiation], the cumulative probability of confirmed virological failure by 42 months on ART was 6.3%. Using targeted viral load after meeting DHHS immunological failure criteria rather than DHHS immunological failure criteria alone increased positive predictive value from 28% to 82%. Targeted viral load improved the positive predictive value of WHO 2010 criteria for identifying confirmed virological failure from 49% to 82%. Conclusion  The addition of a single viral load measurement in children identified as failing immunologically will prevent most switches to second-line treatment in virologically suppressed children.
    • Screening of patients with diabetes mellitus for tuberculosis in India

      Kumar, A; Gupta, D; Nagaraja, S B; Nair, S A; Satyanarayana, S; Zachariah, R; Harries, A D (Blackwell Publishing Ltd, 2013-05)
      To assess the feasibility, results and challenges of screening patients with diabetes mellitus (DM) for tuberculosis (TB) within the healthcare setting of six DM clinics in tertiary hospitals across India.
    • Screening of patients with tuberculosis for diabetes mellitus in China.

      Li, L; Lin, Y; Mi, F; Tan, S; Liang, B; Guo, C; Shi, L; Liu, L; Gong, F; Li, Y; et al. (2012-07-25)
      Objective  There is a high burden of both diabetes (DM) and tuberculosis (TB) in China, and this study aimed to assess feasibility and results of screening patients with TB for DM within the routine healthcare setting of six health facilities. Method  Agreement on how to screen, monitor and record was reached in May 2011 at a stakeholders' meeting, and training was carried out for staff in the six facilities in July 2011. Implementation started in September 2011, and we report on 7 months of activities up to 31 March 2012. Results  There were 8886 registered patients with TB. They were first asked whether they had DM. If the answer was no, they were screened with a random blood glucose (RBG) followed by fasting blood glucose (FBG) in those with RBG ≥ 6.1 mm (one facility) or with an initial FBG (five facilities). Those with FBG ≥ 7.0 mm were referred to DM clinics for diagnostic confirmation with a second FBG. Altogether, 1090 (12.4%) patients with DM were identified, of whom 863 (9.7%) had a known diagnosis of DM. Of 8023 patients who needed screening for DM, 7947 (99%) were screened. This resulted in a new diagnosis of DM in 227 patients (2.9% of screened patients), and of these, 226 were enrolled to DM care. In addition, 575 (7.8%) persons had impaired fasting glucose (FBG 6.1 to <7.0 mm). Prevalence of DM was significantly higher in patients in health facilities serving urban populations (14.0%) than rural populations (10.6%) and higher in hospital patients (13.5%) than those attending TB clinics (8.5%). Conclusion  This pilot project shows that it is feasible to screen patients with TB for DM in the routine setting, resulting in a high yield of patients with known and newly diagnosed disease. Free blood tests for glucose measurement and integration of TB and DM services may improve the diagnosis and management of dually affected patients.
    • Screening of patients with tuberculosis for diabetes mellitus in India

      Kumar, A; Jain, D C; Gupta, D; Satyanarayana, S; Zachariah, R; Harries, A D (2013-05)
      To assess feasibility and results of screening patients with tuberculosis (TB) for diabetes mellitus (DM) within the routine healthcare setting across the country at: eight tertiary care hospitals and more than 60 peripheral health institutions in eight tuberculosis units.
    • Short communication: antituberculosis drug-induced hepatotoxicity is unexpectedly low in HIV-infected pulmonary tuberculosis patients in Malawi.

      Tostmann, A; Boeree, M J; Harries, A D; Sauvageot, D; Banda, H T; Zijlstra, E E; Department of Pulmonary Diseases, Radboud University Nijmegen Medical Centre and University Lung Centre Dekkerswald, Nijmegen, The Netherlands. A.Tostmann@ulc.umcn.nl (2007-07)
      The proportion of patients with antituberculosis drug-induced hepatotoxicity (ATDH) was unexpectedly low during a trial on cotrimoxazole prophylaxis in Malawian HIV-positive pulmonary tuberculosis patients. About 2% of the patients developed grade 2 or 3 hepatotoxicity during tuberculosis (TB) treatment, according to WHO definitions. Data on ATDH in sub-Saharan Africa are limited. Although the numbers are not very strong, our trial and other papers suggest that ATDH is uncommon in this region. These findings are encouraging in that hepatotoxicity may cause less problem than expected, especially in the light of combined HIV/TB treatment, where drug toxicity is a major cause of treatment interruption.
    • Successful expansion of community-based drug-resistant TB care in rural Eswatini - a retrospective cohort study.

      Kerschberger, B; Telnov, A; Yano, N; Cox, H; Zabsonre, I; Kabore, SM; Vambe, D; Ngwenya, S; Rusch, B; Luce, TM; et al. (Wiley-Blackwell, 2019-08-07)
      OBJECTIVES: Provision of drug-resistant tuberculosis (DR-TB) treatment is scarce in resource-limited settings. We assessed the feasibility of ambulatory DR-TB care for treatment expansion in rural Eswatini. METHODS: Retrospective patient-level data were used to evaluate ambulatory DR-TB treatment provision in rural Shiselweni (Eswatini), from 2008 to 2016. DR-TB care was either clinic-based led by nurses or community-based at the patient's home with involvement of community treatment supporters for provision of treatment to patients with difficulties in accessing facilities. We describe programmatic outcomes and used multivariate flexible parametric survival models to assess time to adverse outcomes. Both care models were costed in supplementary analyses. RESULTS: Of 698 patients initiated on DR-TB treatment, 57% were women and 84% were HIV-positive. Treatment initiations increased from 27 in 2008 to 127 in 2011 and decreased thereafter to 51 in 2016. Proportionally, community-based care increased from 19% in 2009 to 77% in 2016. Treatment success was higher for community-based care (79%) than clinic-based care (68%, P = 0.002). After adjustment for covariate factors among adults (n = 552), the risk of adverse outcomes (death, loss to follow-up, treatment failure) in community-based care was reduced by 41% (adjusted hazard ratio 0.59, 95% CI: 0.39-0.91). Findings were supported by sensitivity analyses. The care provider's per-patient costs for community-based (USD13 345) and clinic-based (USD12 990) care were similar. CONCLUSIONS: Ambulatory treatment outcomes were good, and community-based care achieved better treatment outcomes than clinic-based care at comparable costs. Contextualised DR-TB care programmes are feasible and can support treatment expansion in rural settings.
    • Tuberculosis treatment in complex emergencies: are risks outweighing benefits?

      Biot, M; Chandramohan, D; Porter, J D H; MSF Brussels (2003-03)
      Tuberculosis (TB) is a major public health problem in complex emergencies. Humanitarian agencies usually postpone the decision to offer TB treatment and opportunities to treat TB patients are often missed. This paper looks at the problem of tuberculosis treatment in these emergencies and questions whether treatment guidelines could be more flexible than international recommendations. A mathematical model is used to calculate the risks and benefits of different treatment scenarios with increasing default rates. Model outcomes are compared to a situation without treatment. An economic analysis further discusses the findings in a trade-off between the extra costs of treating relapses and failures and the savings in future treatment costs. In complex emergencies, if a TB programme could offer 4-month treatment for 75% of its patients, it could still be considered beneficial in terms of public health. In addition, the proportion of patients following at least 4 months of treatment can be used as an indicator to help evaluate the public health harm and benefit of the TB programme.