• Decentralisation of multidrug-resistant-tuberculosis care and management [letter]

      Cox, H; Ford, N; Médecins Sans Frontières, Cape Town, South Africa; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, South Africa. (Elsevier, 2013-06-03)
    • Decline in national tuberculosis notifications with national scale-up of antiretroviral therapy in Malawi

      Kanyerere, H; Mganga, A; Harries, A D; Tayler-Smith, K; Jahn, A; Chimbwandira, F M; Mpunga, J (International Union Against Tuberculosis and Lung Disease, 2014-06-21)
    • Defining the Needs for Next Generation Assays for Tuberculosis

      Denkinger, C M; Kik, S V; Cirillo, D M; Casenghi, M; Shinnick, T; Weyer, K; Gilpin, C; Boehme, C C; Schito, M; Kimerling, M; et al. (Oxford University Press, 2015-04-01)
      To accelerate the fight against tuberculosis, major diagnostic challenges need to be addressed urgently. Post-2015 targets are unlikely to be met without the use of novel diagnostics that are more accurate and can be used closer to where patients first seek care in affordable diagnostic algorithms. This article describes the efforts by the stakeholder community that led to the identification of the high-priority diagnostic needs in tuberculosis. Subsequently target product profiles for the high-priority diagnostic needs were developed and reviewed in a World Health Organization (WHO)-led consensus meeting. The high-priority diagnostic needs included (1) a sputum-based replacement test for smear-microscopy; (2) a non-sputum-based biomarker test for all forms of tuberculosis, ideally suitable for use at levels below microscopy centers; (3) a simple, low cost triage test for use by first-contact care providers as a rule-out test, ideally suitable for use by community health workers; and (4) a rapid drug susceptibility test for use at the microscopy center level. The developed target product profiles, along with complimentary work presented in this supplement, will help to facilitate the interaction between the tuberculosis community and the diagnostics industry with the goal to lead the way toward the post-2015 global tuberculosis targets.
    • Delamanid for rifampicin-resistant tuberculosis: a retrospective study from South Africa.

      Mohr, E; Hughes, J; Reuter, A; Trivino Duran, L; Ferlazzo, G; Daniels, J; De Azevedo, V; Kock, Y; Steele, SJ; Shroufi, A; et al. (European Respiratory Society, 2018-06-14)
      Experience with delamanid (Dlm) is limited, particularly among HIV-positive individuals. We describe early efficacy and safety data from a programmatic setting in South Africa. This was a retrospective cohort study of patients receiving Dlm-containing treatment regimens between November 2015 and August 2017. We report 12-month interim outcomes, sputum culture conversion (SCC) by months 2 and 6, serious adverse events (SAEs) and QT intervals corrected using the Frederica formula (QTcF). Overall, 103 patients were initiated on Dlm; 79 (77%) were HIV positive. The main indication for Dlm was intolerance to second-line anti-tuberculosis (TB) drugs (n=58, 56%). There were 12 months of follow-up for 46 patients; 28 (61%) had a favourable outcome (cure, treatment completion or culture negativity). Positive cultures were found for 57 patients at Dlm initiation; 16 out of 31 (52%) had SCC within 2 months and 25 out of 31 (81%) within 6 months. There were 67 SAEs reported in 29 patients (28%). There were four instances of QTcF prolongation >500 ms in two patients (2%), leading to permanent discontinuation in one case; however, no cardiac arrhythmias occurred. This large cohort of difficult-to-treat patients receiving Dlm for rifampicin-resistant TB treatment in a programmatic setting with high HIV prevalence had favourable early treatment response and tolerated treatment well. Dlm should remain available, particularly for those who cannot be treated with conventional regimens or with limited treatment options.
    • Demanding an end to tuberculosis: treatment of tuberculosis infection among persons living with and without HIV

      Fargher, J; Reuter, A; Furin, J (Lippincott, Williams & Wilkins, 2019-01-01)
      More than two billion people are infected with Mycobacterium tuberculosis and few of them are ever offered therapy in spite of such treatment being associated with reduced rates of morbidity and mortality. This article reviews the current recommendations on the diagnosis and treatment of TB infection (or what is commonly referred to as 'prophylaxis' or 'preventive therapy' of latent TB) and discusses barriers to implementation that have led to low demand for this life-saving therapeutic intervention.
    • Detecting tuberculosis: rapid tools but slow progress

      England, K; Masini, T; Rajardo, E (International Union Against Tuberculosis and Lung Disease, 2019-09-21)
      The World Health Organization (WHO) currently recommends Xpert® MTB/RIF as the initial test for all people with presumptive tuberculosis (TB). A number of challenges have been reported, however, in using this technology, particularly in low-resource settings. Here we examine these challenges, and provide our perspective of the barriers to Xpert scale-up as assessed through a survey in 16 TB burden countries in which the Médecins Sans Frontières is present. We observed that the key barriers to scale-up include a lack of policy adoption and implementation of WHO recommendations for the use of Xpert, resulting from high costs, poor sensitisation of clinical staff and a high turnover of trained laboratory staff; insufficient service and maintenance provision provided by the manufacturer; and inadequate resources for sustainability and expansion. Funding is a critical issue as countries begin to transition out of support from the Global Fund. While it is clear that there is still an urgent need for research into and development of a rapid, affordable point-of-care test for TB that is truly adapted for use in low-resource settings, countries in the meantime need to develop functional and sustainable Xpert networks in order to close the existing diagnostic gap.
    • Detection and Quantification of Mycobacterium Tuberculosis in the Sputum of Culture-Negative HIV-infected Pulmonary Tuberculosis Suspects: A Proof-of-Concept Study

      Madico, G; Mpeirwe, M; White, L; Vinhas, S; Orr, B; Orikiriza, P; Miller, N S; Gaeddert, M; Mwanga-Amumpaire, J; Palaci, M; et al. (Public Library of Science, 2016-07-08)
      Rapid diagnosis of pulmonary tuberculosis (TB) is critical for timely initiation of treatment and interruption of transmission. Yet, despite recent advances, many patients remain undiagnosed. Culture, usually considered the most sensitive diagnostic method, is sub-optimal for paucibacillary disease.
    • Detection of drug-resistant tuberculosis by Xpert MTB/RIF in Swaziland

      Sanchez-Padilla, E; Merker, M; Beckert, P; Jochims, F; Dlamini, T; Kahn, P; Bonnet, M; Niemann, S (Massachusetts Medical Society, 2015-03-19)
    • The devil we know: is the use of injectable agents for the treatment of MDR-TB justified?

      Reuter, A; Tisile, P; von Delft, D; Cox, H; Cox, V; Ditiu, L; Garcia-Prats, A; Koenig, S; Lessem, E; Nathavitharana, R; et al. (International Union Against Tuberculosis and Lung Disease, 2017-11-01)
      For decades, second-line injectable agents (IAs) have been the cornerstone of treatment for multidrug-resistant tuberculosis (MDR-TB). Although evidence on the efficacy of IAs is limited, there is an expanding body of evidence on the serious adverse events caused by these drugs. Here, we present the results of a structured literature review of the safety and efficacy of IAs. We review the continued widespread use of these agents in the context of therapeutic alternatives-most notably the newer TB drugs, bedaquiline and delamanid-and from the context of human rights, ethics and patient-centered care. We conclude that there is limited evidence of the efficacy of IAs, clear evidence of the risks of these drugs, and that persons living with MDR-TB should be informed about these risks and provided with access to alternative therapeutic options.
    • Diabetes mellitus and smoking among tuberculosis patients in a tertiary care centre in Karnataka, India

      Jali, M V; Mahishale, V K; Hiremath, M B; Satyanarayana, S; Kumar, A M V; Nagaraja, S B; Isaakidis, P (International Union Against TB and Lung Disease, 2013-11)
    • Diabetes Mellitus and Tuberculosis: Programmatic Management Issues

      Harries, A D; Kumar, A M V; Satyanarayana, S; Lin, Y; Zachariah, R; Lönnroth, K; Kapur, A (International Union Against Tuberculosis and Lung Disease, 2015-08-01)
      In August 2011, the World Health Organization and the International Union Against Tuberculosis and Lung Disease launched the Collaborative Framework for Care and Control of Tuberculosis (TB) and diabetes mellitus (DM) to guide policy makers and implementers in combatting the epidemics of both diseases. Progress has been made, and includes identifying how best to undertake bidirectional screening for both diseases, how to provide optimal treatment and care for patients with dual disease and the most suitable framework for monitoring and evaluation. Key programmatic challenges include the following: whether screening should be directed at all patients or targeted at those with high-risk characteristics; the most suitable technologies for diagnosing TB and diabetes in routine settings; the best time to screen TB patients for DM; how to provide an integrated, coordinated approach to case management; and finally, how to persuade non-communicable disease programmes to adopt a cohort analysis approach, preferably using electronic medical records, for monitoring and evaluation. The link between DM and TB and the implementation of the collaborative framework for care and control have the potential to stimulate and strengthen the scale-up of non-communicable disease care and prevention programmes, which may help in reducing not only the global burden of DM but also the global burden of TB.
    • Diagnosis and management of drug-resistant tuberculosis in South African adults

      Hughes, J; Osman, M (Health & Medical Publishing Group, 2014-12)
    • 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.
    • Diagnostic management and outcomes of pulmonary tuberculosis suspects admitted to a central hospital in Malawi

      Gawa, L G; Reid, T; Edginton, M E; Van Lettow, M; Joshua, M; Harries, A D (TB Union, 2012-01-25)
    • Diagnostic sensitivity of SILVAMP TB-LAM (FujiLAM) point-of-care urine assay for extra-pulmonary tuberculosis in people living with HIV

      Kerkhoff, AD; Sossen, B; Schutz, C; Reipold, EI; Trollip, A; Moreau, E; Schumacher, SG; Burton, R; Ward, A; Nicol, MP; et al. (European Respiratory Society, 2019-11-07)
    • Direct microscopy versus sputum cytology analysis and bleach sedimentation for diagnosis of tuberculosis: a prospective diagnostic study.

      Hepple, P; Nguele, P; Greig, J; Bonnet, M; Sizaire, V (2010-09-21)
      ABSTRACT: BACKGROUND: Diagnostic options for pulmonary tuberculosis in resource-poor settings are commonly limited to smear microscopy. We investigated whether bleach concentration by sedimentation and sputum cytology analysis (SCA) increased the positivity rate of smear microscopy for smear-positive tuberculosis. METHODS: We did a prospective diagnostic study in a Medecins Sans Frontieres-supported hospital in Mindouli, Republic of Congo. Three sputum samples were obtained from 280 consecutive pulmonary tuberculosis suspects, and were processed according to WHO guidelines for direct smear microscopy. The remainder of each sputum sample was homogenised with 2.6% bleach, sedimented overnight, smeared, and examined blinded to the direct smear result for acid-fast bacilli (AFB). All direct smears were assessed for quality by SCA. If a patient produced fewer than three good-quality sputum samples, further samples were requested. Sediment smear examination was performed independently of SCA result on the corresponding direct smear. Positivity rates were compared using McNemar's test. RESULTS: Excluding SCA, 43.2% of all patients were diagnosed as positive on direct microscopy of up to three samples. 47.9% were diagnosed on sediment microscopy, with 48.2% being diagnosed on direct microscopy, sediment microscopy, or both. The positivity rate increased from 43.2% to 47.9% with a case definition of one positive smear ([greater than or equal to]1 AFB/100 high power fields) of three, and from 42.1% to 43.9% with two positive smears. SCA resulted in 87.9% of patients producing at least two good-quality sputum samples, with 75.7% producing three or more. Using a case definition of one positive smear, the incremental yield of bleach sedimentation was 14/121, or 11.6% (95% CI 6.5-18.6, p=0.001) and in combination with SCA was 15/121, or 12.4% (95% CI 7.1-19.6, p=0.002). Incremental yields with two positive smears were 5/118, or 4.2% (95% CI 1.4-9.6, p=0.062) and 7/118, or 5.9% (95% CI 2.4-11.8, p=0.016), respectively. CONCLUSIONS: The combination of bleach sedimentation and SCA resulted in significantly increased microscopy positivity rates with a case definition of either one or two positive smears. Implementation of bleach sedimentation led to a significant increase in the diagnosis of smear-positive patients. Implementation of SCA did not result in significantly increased diagnosis of tuberculosis, but did result in improved sample quality. Requesting extra sputum samples based on SCA results, combined with bleach sedimentation, could significantly increase the detection of smear-positive patients if routinely implemented in resource-limited settings where gold standard techniques are not available. We recommend that a pilot phase is undertaken before routine implementation to determine the impact in a particular context.
    • Direct Observation (DO) for Drug-Resistant Tuberculosis: Do We Really DO?

      Benbaba, S; Isaakidis, P; Das, M; Jadhav, S; Reid, T; Furin, J (2015-12-29)
      Directly-observed therapy (DOT) is recommended for drug-resistant tuberculosis (DR-TB) patients during their entire treatment duration. However, there is limited published evidence on implementation of direct observation (DO) in the field. This study aims to detail whether DO was followed with DR-TB patients in a Médecins Sans Frontières (MSF) tuberculosis program in Mumbai, India.
    • Directly-observed and self-administered tuberculosis treatment in a chronic, low-intensity conflict setting in India

      Das, M; Isaakidis, P; Armstrong, E; Gundipudi, N R; Babu, R B; Qureshi, I A; Claes, A; Mudimanchi, A K; Prasad, N; Mansoor, H; et al. (Public Library of Science, 2014)
      Limited data are available about tuberculosis treatment models of care for internally displaced populations in chronic, low-intensity conflict zones. This study aimed to detail experiences of a Médecins Sans Frontières tuberculosis programme in Andhra Pradesh-Chhattisgarh border area, India, from January to December 2012.
    • Dispatches From Abroad: Aground in a Sea of TB.

      Kittle, D; MSF Aral Sea Area Program, Uzbekistan. (Published by the Canadian Medical Association, 2000-12-12)
    • Disseminated Tuberculosis Among Hospitalised HIV Patients in South Africa: A Common Condition that Can Be Rapidly Diagnosed Using Urine-Based Assays

      Kerkhoff, A; Barr, D; Schutz, C; Burton, R; Nicol, M; Lawn, S; Meintjes, G (Nature Publishing Group, 2017-09-07)
      HIV-associated disseminated TB (tuberculosis) has been under-recognised and poorly characterised. Blood culture is the gold-standard diagnostic test, but is expensive, slow, and may under-diagnose TB dissemination. In a cohort of hospitalised HIV patients, we aimed to report the prevalence of TB-blood-culture positivity, performance of rapid diagnostics as diagnostic surrogates, and better characterise the clinical phenotype of disseminated TB. HIV-inpatients were systematically investigated using sputum, urine and blood testing. Overall, 132/410 (32.2%) patients had confirmed TB; 41/132 (31.1%) had a positive TB blood culture, of these 9/41 (22.0%) died within 90-days. In contrast to sputum diagnostics, urine Xpert and urine-lipoarabinomannan (LAM) combined identified 88% of TB blood-culture-positive patients, including 9/9 who died within 90-days. For confirmed-TB patients, half the variation in major clinical variables was captured on two principle components (PCs). Urine Xpert, urine LAM and TB-blood-culture positive patients clustered similarly on these axes, distinctly from patients with localised disease. Total number of positive tests from urine Xpert, urine LAM and MTB-blood-culture correlated with PCs (p < 0.001 for both). PC1&PC2 independently predicted 90-day mortality (ORs 2.6, 95%CI = 1.3-6.4; and 2.4, 95%CI = 1.3-4.5, respectively). Rather than being a non-specific diagnosis, disseminated TB is a distinct, life-threatening condition, which can be diagnosed using rapid urine-based tests, and warrants specific interventional trials.