• Added value of bleach sedimentation microscopy for diagnosis of tuberculosis: a cost-effectiveness study.

      Bonnet, M; Tajahmady, A; Hepple, P; Ramsay, A; Githui, W; Gagdnidze, L; Guérin, P J; Varaine, F; Epicentre, Paris, France; Mission Nationale d’Expertise et d’Audit Hospitaliers, Paris, France; Manson Unit, Médecins Sans Frontières, London, UK; Liverpool School of Tropical Medicine, Liverpool, UK; United Nation’s Children’s Fund/United Nations Development Programme/World Bank/World Health Organization Special Programme for Research and Training for Tropical Diseases, Geneva, Switzerland; Centre for Respiratory Diseases Research, Kenya Medical Research Institute, Nairobi, Kenya; Médecins Sans Frontières, Paris, France (2010-04-09)
      SETTING: Bleach sedimentation is a method used to increase the diagnostic yield of sputum microscopy for countries with a high prevalence of human immunodeficiency virus (HIV) infection and limited resources. OBJECTIVES: To compare the relative cost-effectiveness of different microscopy approaches in diagnosing tuberculosis (TB) in Kenya. METHODS: An analytical decision tree model including cost and effectiveness measures of 10 combinations of direct (D) and overnight bleach (B) sedimentation microscopy was constructed. Data were drawn from the evaluation of the bleach sedimentation method on two specimens (first on the spot [1] and second morning [2]) from 644 TB suspects in a peripheral health clinic. Incremental cost per smear-positive detected case was measured. Costs included human resources and materials using a micro-costing evaluation. RESULTS: All bleach-based microscopy approaches detected significantly more cases (between 23.3% for B1 and 25.9% for B1+B2) than the conventional D1+D2 approach (21.0%). Cost per tested case ranged between respectively euro 2.7 and euro 4.5 for B1 and B1+D2+B2. B1 and B1+B2 were the most cost-effective approaches. D1+B2 and D1+B1 were good alternatives to avoid using approaches exclusively based on bleach sedimentation microscopy. CONCLUSIONS: Among several effective microscopy approaches used, including sodium hypochlorite sedimentation, only some resulted in a limited increase in the laboratory workload and would be most suitable for programmatic implementation.
    • Adverse events among people on delamanid for rifampicin-resistant tuberculosis in a high HIV prevalence setting

      Hughes, J; Reuter, A; Chabalala, B; Isaakidis, P; Cox, H; Mohr, E (International Union Against Tuberculosis and Lung Disease, 2019-09-01)
      SETTING: Patients with rifampicin-resistant tuberculosis (RR-TB) in the township of Khayelitsha, South Africa, were offered delamanid (DLM) within a decentralised RR-TB treatment programme. OBJECTIVE: To describe adverse events (AEs) among HIV-positive and negative people receiving DLM for RR-TB in a programmatic setting. DESIGN: Patients were followed up monthly for blood, electrocardiography and clinical monitoring and AEs were assessed for severity grade, seriousness and relationship to DLM. RESULTS: Fifty-eight patients (55% male; median age 35 years, interquartile range [IQR] 28–42) started DLM; 46 (79%) were HIV-positive, median CD4 count 173 cells/mm3 (IQR 70–294). Fifty (86%) patients experienced ≥1 new or worsening AE after starting DLM, most commonly vomiting, QTcB >450 ms and/or myalgia. Serious and/or severe AEs were experienced by 22 (38%) patients; three HIV-positive patients died (not related to DLM). HIV status was not significantly associated with number (P = 0.089) or severity/seriousness (P = 0.11) of AEs during exposure to DLM. Two (3%) patients had DLM withdrawn due to AEs. CONCLUSION: AEs during RR-TB treatment, both before and during DLM exposure, were common, with relatively few serious/severe AEs considered related to DLM and no significant association with HIV status. Clinical and electrocardiography monitoring should be prioritised in the first two months after starting DLM.
    • Ambulatory tuberculosis treatment in post-Semashko health care systems needs supportive financing mechanisms

      Kohler, S; Asadov, D A; Bründer, A; Healy, S; Khamraev, A K; Sergeeva, N; Tinnemann, P (International Union Against Tuberculosis and Lung Disease, 2014-12-01)
      The tuberculosis (TB) control strategy in the Republic of Karakalpakstan, Uzbekistan, is being changed to decentralised out-patient care for most TB patients by the Government of Uzbekistan, in collaboration with the international medical humanitarian organisation Médecins Sans Frontières. Ambulatory treatment of both drug-susceptible and drug-resistant TB from the first day of treatment has been recommended since 2011. Out-patient treatment of TB from the beginning of treatment was previously prohibited. However, the current Uzbek health financing system, which evolved from the Soviet Semashko model, offers incentives that work against the adoption of ambulatory TB treatment. Based on the 'Comprehensive TB Care for All' programme implemented in Karakalpakstan, we describe how existing policies for the allocation of health funds complicate the scale-up of ambulatory-based management of TB.
    • Can We Get More HIV-Positive Tuberculosis Patients on Antiretroviral Treatment in a Rural District of Malawi?

      Zachariah, R; Teck, R; Ascurra, O; Gomani, P; Manzi, M; Humblet, P; Nunn, P; Salaniponi, F M L; Harries, A D; Medical Department (HIV-TB Operational Research), Brussels Operational Centre, Médecins sans Frontières, Brussels, Belgium. zachariah@internet.lu (International Union Against TB and Lung Disease, 2005-03)
      The World Health Organization (WHO) has set a target of treating 3 million people with antiretroviral treatment (ART) by 2005. In sub-Saharan Africa, HIV-positive tuberculosis (TB) patients could significantly contribute to this target. ART (stavudine/lamivudine/nevirapine) was initiated in Thyolo district, Malawi, in April 2003, and all HIV-positive TB patients were considered eligible and offered ART. Despite this, only 44 (13%) of 352 TB patients were eventually started on ART by the end of November 2003. Most TB patients leave hospital after 2 weeks to complete the initial phase of anti-tuberculosis treatment (rifampicin-based) in the community, and ART is offered to HIV-positive TB patients after they have started the continuation phase of treatment (isoniazid/ ethambutol). ART is only offered at hospital, while the majority of TB patients take their continuation phase of anti-tuberculosis treatment from health centres. HIV-positive TB patients therefore find it difficult to access ART. In this paper, we discuss a series of options to increase the uptake of ART among HIV-positive TB patients. The main options are: 1) to hospitalise HIV-positive TB patients with a view to starting ART in the continuation phase in hospital; 2) to decentralise ART delivery so ART can be delivered at health centres; 3) to replace nevirapine with efavirenz so ART can be started earlier in the initial phase of anti-tuberculosis treatment. Decentralisation of ART from hospitals to health centres would greatly improve ART access.
    • Compliance with Cotrimoxazole Prophylaxis for the Prevention of Opportunistic Infections in HIV-Positive Tuberculosis Patients in Thyolo District, Malawi.

      Zachariah, R; Harries, A D; Arendt, V; Wennig, R; Schneider, S; Spielmann M P; Panarotto, E; Gomani, P; Salaniponi, F M L; Medecins sans Frontieres-Luxembourg, Thyolo District, Malawi. msflblantyre@malawi.net (International Union Against TB and Lung Disease, 2001-09)
      OBJECTIVE: To verify compliance with cotrimoxazole prophylaxis in human immunodeficiency virus (HIV) infected tuberculosis (TB) patients during the continuation phase of anti-tuberculosis treatment, and to assess the sensitivity, specificity and positive predictive values of verbal verification and pill counts as methods of checking compliance. DESIGN: Cross-sectional study. METHODS: Cotrimoxazole compliance was assessed in a cohort of TB patients who were attending four TB follow-up centres during the continuation phase of anti-TB treatment between months 4 and 6. Verbal verification of drug intake, physical verification of pill count balance, and urine trimethoprim detection by gas chromatography and mass spectrometry were used for assessing compliance. RESULTS: Using urine trimethoprim detection as the gold standard for compliance, trimethoprim was detected in 82 (94%) of 87 patients in the cohort. Verbal verification of cotrimoxazole intake and objective pill count balances showed high sensitivity and positive predictive values compared with the gold standard of urine trimethoprim detection. CONCLUSIONS: In a rural district in Malawi, compliance with cotrimoxazole as an adjunct to anti-tuberculosis treatment in HIV-infected TB patients was good, and can be assessed simply and practically by verbal verification and pill counts.
    • Cotrimoxazole prophylaxis in HIV-infected individuals after completing anti-tuberculosis treatment in Thyolo, Malawi.

      Zachariah, R; Spielmann M P; Harries, A D; Gomani, P; Bakali, E; Médecins Sans Frontières-Luxembourg, Thyolo, Thyolo District, Malawi. zachariah@internet.lu (2002-12)
      SETTING: Thyolo, rural southern Malawi. OBJECTIVES: To determine 1) the proportion who continue with cotrimoxazole prophylaxis for the prevention of opportunistic infections, and 2) the reasons for continuing or stopping prophylaxis, in human immunodeficiency virus (HIV) infected individuals with tuberculosis (TB) who complete anti-tuberculosis treatment. DESIGN: A cross-sectional study. METHODS: A questionnaire study of all HIV-infected TB patients who had been registered over a 3-month period to receive anti-tuberculosis treatment and cotrimoxazole prophylaxis and who had completed antituberculosis treatment 3-6 months earlier. RESULTS: Of 82 HIV-infected individuals who were alive at the time of interview, 76 (93%) were continuing with cotrimoxazole and wished to do so indefinitely. The most common reason for continuing the drug was to prevent illness associated with HIV, while the most common reason for stopping was long distances to the health facility. Ninety-six percent of patients received cotrimoxazole free of charge from a health centre. Of those who wished to continue indefinitely, the majority (63%) could not afford to pay for the drug. CONCLUSIONS: In a rural setting, the great majority of HIV-infected individuals continued with cotrimoxazole after completing anti-tuberculosis treatment. Making the drug available and providing it free of charge is essential if it is to remain accessible for longer term prevention.
    • 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.
    • Does Antiretroviral Treatment Reduce Case Fatality Among HIV-Positive Patients with Tuberculosis in Malawi?

      Zachariah, R; Fitzgerald, M; Massaquoi, M; Acabu, A; Chilomo, D; Salaniponi, F M L; Harries, A D; Medical Department (Operational Research), Médecins sans Frontières, Brussels Operational Centre, Luxembourg. zachariah@internet.lu (2007-08)
      SETTING: Thyolo district, Malawi. OBJECTIVES: To report on 1) case fatality among human immunodeficiency virus (HIV) positive tuberculosis (TB) patients while on anti-tuberculosis treatment and 2) whether antiretroviral treatment (ART) initiated during the continuation phase of TB treatment reduces case fatality. DESIGN: Retrospective cohort analysis. METHODS: Comparative analysis of treatment outcomes for TB patients registered between January and December 2004. RESULTS: Of 983 newly registered TB patients receiving diagnostic HIV testing, 658 (67%) were HIV-positive. A total of 132 (20%) patients died during the 8-month course of anti-tuberculosis treatment, of whom 82 (62%) died within the first 2 months of treatment when ART was not provided (cumulative incidence 3.0, 95%CI 2.5-3.6 per 100 person-years). A total of 576 TB patients started the continuation phase of anti-tuberculosis treatment, 180 (31%) of whom were started on ART. The case-fatality rate per 100 person-years was not significantly different for patients on ART (1.0, 95%CI 0.6-1.7) and those without ART (1.2, 95%CI 0.9-1.7, adjusted hazard ratio 0.86, 95%CI 0.4-1.6, P = 0.6) CONCLUSIONS: ART provided in the continuation phase of TB treatment does not have a significant impact on reducing case fatality. Reasons for this and possible measures to reduce high case fatality in the initial phase of TB treatment are discussed.
    • Does One Size Fit All? Drug Resistance and Standard Treatments: Results of Six Tuberculosis Programmes in Former Soviet Countries.

      Bonnet, M; Sizaire, V; Kebede, Y; Janin, A; Doshetov, D; Mirzoian, B; Arzumanian, A; Muminov, T; Iona, E; Rigouts, L; et al. (International Union Against TB and Lung Disease, 2005-10)
      SETTING: After the collapse of the Soviet Union, countries in the region faced a dramatic increase in tuberculosis cases and the emergence of drug resistance. OBJECTIVE: To discuss the relevance of the DOTS strategy in settings with a high prevalence of drug resistance. DESIGN: Retrospective analysis of one-year treatment outcomes of short-course chemotherapy (SCC) and results of drug susceptibility testing (DST) surveys of six programmes located in the former Soviet Union: Kemerovo prison, Russia; Abkhasia, Georgia; Nagorno-Karabagh, Azerbaijan; Karakalpakstan, Uzbekistan; Dashoguz Velayat, Turkmenistan; and South Kazakhstan Oblast, Kazakhstan. Results are reported for new and previously treated smear-positive patients. RESULTS: Treatment outcomes of 3090 patients and DST results of 1383 patients were collected. Treatment success rates ranged between 87% and 61%, in Nagorno-Karabagh and Kemerovo, respectively, and failure rates between 7% and 23%. Any drug resistance ranged between 66% and 31% in the same programmes. MDR rates ranged between 28% in Karakalpakstan and Kemerovo prison and 4% in Nagorno-Karabagh. CONCLUSION: These results show the limits of SCC in settings with a high prevalence of drug resistance. They demonstrate that adapting treatment according to resistance patterns, access to reliable culture, DST and good quality second-line drugs are necessary.
    • Ending Tuberculosis by 2030: Can We Do It?

      Suthar, A B; Zachariah, R; Harries, A D (International Union Against TB and Lung Disease, 2016-06-30)
      The Sustainable Development Goals aim to end tuberculosis (TB) related deaths, transmission and catastrophic costs by 2030. Multisectorial action to accelerate socio-economic development, a new vaccine and novel diagnostics and medicines for treatment are key advances needed to end TB transmission. Achieving 90-90-90 targets for TB (i.e., 90% of vulnerable populations screened, 90% diagnosed and started on treatment, and at least 90% cured) will help accelerate progress towards reductions in mortality; however, passive case detection strategies, multidrug-resistant TB, human immunodeficiency virus coinfection and outdated pathways to care need to be overcome. Ending the catastrophic costs associated with TB will require expansion of health insurance coverage, comprehensive coverage of TB services, and limited indirect costs by vulnerable and poor populations.
    • Evaluation of FASTPlaqueTB to diagnose smear-negative tuberculosis in a peripheral clinic in Kenya

      Bonnet, M; Gagnidze, L; Varaine, F; Ramsay, A; Githui, W; Guerin, P J; Epicentre, Paris, France; Liverpool School of Tropical Medicine, Liverpool, UK; United Nations Children’s Fund/United Nations Development Programme/World Bank/World Health Organization Special Programme for Research and Training for Tropical Diseases (TDR), Geneva, Switzerland; Centre for Respiratory Diseases Research, Kenya Medical Research Institute, Nairobi, Kenya (2009-09-01)
      OBJECTIVE: To evaluate the performance and feasibility of FASTPlaqueTB in smear-negative tuberculosis (TB) suspects in a peripheral clinic after laboratory upgrading. DESIGN: Patients with cough > or=2 weeks, two sputum smear-negative results, no response to 1 week of amoxicillin and abnormal chest X-ray were defined as smear-negative suspects. One sputum sample was collected, decontaminated and divided into two: half was tested with FASTPlaqueTB in the clinic laboratory and the other half was cultured on Löwenstein-Jensen medium in the Kenyan Medical Research Institute. Test sensitivity and specificity were evaluated in all patients and in human immunodeficiency virus (HIV) infected patients. Feasibility was assessed by the contamination rate and the resources required to upgrade the laboratory. RESULTS: Of 208 patients included in the study, 56.2% were HIV-infected. Of 203 FASTPlaqueTB tests, 95 (46.8%) were contaminated, which interfered with result interpretation and led to the interruption of the study. Sensitivity and specificity were respectively 31.2% (95%CI 12.1-58.5) and 94.9% (95%CI 86.8-98.4) in all patients and 33.3% (95%CI 9.9-65.1) and 93.9% (95%CI 83.1-98.7) in HIV-infected patients. Upgrading the laboratory cost euro 20,000. CONCLUSION: FASTPlaqueTB did not perform satisfactorily in this setting. If contamination can be reduced, in addition to laboratory upgrading, its introduction in peripheral clinics would require further assessment in smear-negative and HIV co-infected patients and test adaptation for friendlier use.
    • The experience of implementing a 'TB village' for a pastoralist population in Cherrati, Ethiopia

      Tayler-Smith, K; Khogali, M; Keiluhu, K; Jemmy, J-P; Ayada, L; Weyeyso, T; Issa, A M; De Maio, G; Harries, A D; Zachariah, R (2011-09)
    • False-positive Xpert(®) MTB/RIF assays and previous treatment

      Boyles, T H; Hughes, J; Cox, V; Burton, R; Meintjes, G; Mendelson, M (International Union Against Tuberculosis and Lung Disease, 2015-04)
    • False-positive Xpert(®) MTB/RIF assays in previously treated patients: need for caution in interpreting results.

      Boyles, T H; Hughes, J; Cox, V; Burton, R; Meintjes, G; Mendelson, M (2014-07)
      Xpert(®) MTB/RIF is the initial diagnostic test of choice for tuberculosis (TB). It is not known if false-positive results are more common in previously treated patients. We report four patients with successful treatment for TB up to 5 years previously who presented with respiratory tract infection and were Xpert-positive, but had negative TB cultures and clinical improvement without anti-tuberculosis treatment. We hypothesise that the Xpert results were false-positive due to the presence of dead Mycobacterium tuberculosis bacilli in lungs and sputum. Further work is required to determine the specificity of Xpert in previously treated patients.
    • Hepple - Microscopy compared to culture for the diagnosis of Tuberculosis in Induced Sputum samples; a systematic review

      Hepple, P; Ford, N; McNerney, R; Manson Unit, Médecins Sans Frontières, London, UK. pamela.hepple@london.msf.org (2012-03-07)
      Resource-limited settings rely on sputum examination using microscopy to diagnose tuberculosis (TB); however, the sensitivity of the test is poor and case detection rates are low. Sputum induction is proposed as a way to improve sample collection and enhance test sensitivity.
    • 'I didn't know so many people cared about me': support for patients who interrupt drug-resistant TB treatment.

      Snyman, L; Venables, E; Trivino Duran, L; Mohr, E; Harmans, X; Isaakidis, P; Azevedo, VD (International Union Against Tuberculosis and Lung Disease, 2018-09-01)
      SETTING: Early interventions for patients who interrupt their treatment for drug-resistant tuberculosis (DR-TB) are rarely reported and assessed. A novel, patient-centred intervention for patients at risk of loss to follow-up (LTFU) from DR-TB treatment was implemented in Khayelitsha, South Africa, in September 2013. OBJECTIVE: To explore the experiences and perceptions of patients, key support persons, health care workers (HCWs) and programme managers of a patient-centred model. DESIGN: This was a qualitative study consisting of 18 in-depth interviews with patients, key support persons, HCWs, key informants and one focus group discussion with HCWs, between July and September 2017. Data were coded and thematically analysed. RESULTS: The model was well perceived and viewed positively by patients, care providers and programme managers. 'Normalisation' and tolerance of occasional treatment interruptions, tracing, tailored management plans and peer support were perceived to be beneficial for retaining patients in care. Although the model was resource-demanding, health workers were convinced that it 'needs to be sustained,' and proposed solutions for its standardisation. CONCLUSION: An intervention based on early tracing of patients who interrupt treatment, peer-delivered counselling and individualised management plans by a multidisciplinary team was considered a beneficial and acceptable model to support patients at risk of LTFU from DR-TB treatment.
    • 'I'm fed up': experiences of prior anti-tuberculosis treatment in patients with drug-resistant tuberculosis and HIV

      Furin, J; Isaakidis, P; Reid, A J; Kielmann, K (International Union Against Tuberculosis and Lung Disease, 2014-10-03)
      To understand the impact of past experiences of anti-tuberculosis treatment among patients co-infected with the human immunodeficiency virus and multidrug-resistant tuberculosis (MDR-TB) on perceptions and attitudes towards treatment.
    • Identification of Patients Who Could Benefit from Bedaquiline or Delamanid: a Multisite MDR-TB Cohort Study

      Bonnet, M; Bastard, M; du Cros, P; Khamraev, A; Kimenye, K; Khurkhumal, S; Hayrapetyan, A; Themba, D; Telnov, A; Sanchez-Padilla, E; et al. (International Union Against TB and Lung Disease, 2016-02-01)
      The World Health Organization recommends adding bedaquiline or delamanid to multidrug-resistant tuberculosis (MDR-TB) regimens for which four effective drugs are not available, and delamanid for patients at high risk of poor outcome.
    • Impact of introducing human immunodeficiency virus testing, treatment and care in a tuberculosis clinic in rural Kenya

      Huerga, H; Spillane, H; Guerrero, W; Odongo, A; Varaine, F; Médecins Sans Frontières, Nairobi, Kenya; National Tuberculosis Programme, Homa Bay, Kenya; Médecins Sans Frontières, Paris, France (2010-04-09)
      SETTING: In July 2005, Médecins Sans Frontières and the Ministry of Health, Kenya, implemented an integrated tuberculosis-human immunodeficiency virus (TB-HIV) programme in western Kenya. OBJECTIVE: To evaluate the impact of an integrated TB-HIV programme on patient care and TB programme outcomes. DESIGN: Retrospective evaluation of three time periods: before (January-June 2005), shortly after (January-June 2006) and medium term after (January-December 2007) the implementation of the integrated programme. RESULTS: Respectively 79% and 91% of TB patients were HIV tested shortly and at medium term after service integration. The HIV-positive rate varied from 96% before the intervention to respectively 88% (305/347) and 74% (301/405) after. The estimated number of HIV-positive cases was respectively 303, 323 and 331 in the three periods. The proportion of patients receiving cotrimoxazole prophylaxis increased significantly from 47% (142/303) to 94% (303/323) and 86% (285/331, P < 0.05). Before the intervention, 87% (171/197) of the TB-HIV patients would have been missed when initiating antiretroviral treatment, compared to respectively 29% (60/210) and 36% (78/215) after the integration. The TB programme success rate increased from 56% (230/409) to 71% (319/447) in the third period (P < 0.05); however, there was no significant decrease in the default rate: 20% to 22% (P = 0.66) and 18% (P = 0.37). CONCLUSION: Integrated TB-HIV care has a very positive impact on the management of TB-HIV patients and on TB treatment outcomes.