• 10-year assessment of treatment outcome among Cambodian refugees with sputum smear-positive tuberculosis in Khao-I-Dang, Thailand.

      Sukrakanchana-Trikham, P; Puéchal, X; Rigal, J; Rieder, H L; Médecins sans Frontières Tuberculosis Programme, Khao-I-Dang, Prachinburi, Thailand. (International Union Against Tuberculosis and Lung Disease, 1992-12)
      Tuberculosis control among displaced persons is fraught with difficulties to ensure adherence of patients to treatment for a prolonged period of time. In the Khao-I-Dang camp for Cambodian refugees an approach with daily, directly observed treatment throughout the course of 6 months duration was chosen to address the problem. Of a total 929 patients with sputum smear-positive tuberculosis who were enrolled from 1981 to 1990, 5.0% died, 75.5% completed treatment and were bacteriologically cured with a day-to-day adherence of more than 98%, none failed bacteriologically, 19.2% were transferred to another camp where continuation of treatment was guaranteed, and only 0.4% absconded from treatment. These data suggest that the approach to tuberculosis control in this refugee camp was very effective in cutting the chain of transmission of tuberculosis in a highly mobile population and in reducing substantially unnecessary morbidity and mortality.
    • Access to paediatric formulations for the treatment of childhood tuberculosis

      Nash, M; Perrin, C; Seddon, JA; Furin, J; Hauser, J; Marais, B; Kitai, I; Starke, J; McKenna, L (Elsevier, 2020-12-01)
    • 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.
    • Adapting the DOTS framework for tuberculosis control to the management of non-communicable diseases in sub-Saharan Africa

      Harries, A D; Jahn, A; Zachariah, R; Enarson, D; Clinical HIV Unit, Ministry of Health, Lilongwe, Malawi; Family Health International, Malawi Country Office, Lilongwe, Malawi; London School of Hygiene and Tropical Medicine, London, United Kingdom; Lighthouse Trust, Lilongwe, Malawi; International Training and Education Center on HIV, University of Washington, Seattle, WA; Médecins Sans Frontières, Operational Research Medical Department, Luxembourg; International Union against Tuberculosis and Lung Disease, Paris, France (Public Library of Science (PLoS), 2008-06-10)
    • 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.
    • Addressing Diabetes Mellitus as Part of the Strategy for Ending TB

      Harries, A D; Kumar, A M; Satyanarayana, S; Lin, Y; Zachariah, R; Lönnroth, K; Kapur, A (Oxford University Press, 2016-03-01)
      As we enter the new era of Sustainable Development Goals, the international community has committed to ending the TB epidemic by 2030 through implementation of an ambitious strategy to reduce TB-incidence and TB-related mortality and avoiding catastrophic costs for TB-affected families. Diabetes mellitus (DM) triples the risk of TB and increases the probability of adverse TB treatment outcomes such as failure, death and recurrent TB. The rapidly escalating global epidemic of DM means that DM needs to be addressed if TB-related milestones and targets are to be achieved. WHO and the International Union Against Tuberculosis and Lung Disease's Collaborative Framework for Care and Control of Tuberculosis and Diabetes, launched in 2011, provides a template to guide policy makers and implementers to combat the epidemics of both diseases. However, more evidence is required to answer important questions about bi-directional screening, optimal ways of delivering treatment, integration of DM and TB services, and infection control. This should in turn contribute to better and earlier TB case detection, and improved TB treatment outcomes and prevention. DM and TB collaborative care can also help guide the development of a more effective and integrated public health approach for managing non-communicable diseases.
    • Adherence to self-administered tuberculosis treatment in a high HIV-prevalence setting: a cross-sectional survey in Homa Bay, Kenya.

      Nackers, F; Huerga, H; Espié, E; Aloo, A O; Bastard, M; Etard, J-F; Sitienei, J; Varaine, F; Chakaya, J; Bonnet, M; et al. (2012-03-12)
      Good adherence to treatment is crucial to control tuberculosis (TB). Efficiency and feasibility of directly observed therapy (DOT) under routine program conditions have been questioned. As an alternative, Médecins sans Frontières introduced self-administered therapy (SAT) in several TB programs. We aimed to measure adherence to TB treatment among patients receiving TB chemotherapy with fixed dose combination (FDC) under SAT at the Homa Bay district hospital (Kenya). A second objective was to compare the adherence agreement between different assessment tools.
    • Adherence, Tolerability, and Outcome After 36 Months of Isoniazid-Preventive Therapy in 2 Rural Clinics of Swaziland: A Prospective Observational Feasibility Study

      Mueller, Y; Mpala, Q; Kerschberger, B; Rusch, B; Mchunu, G; Mazibuko, S; Bonnet, M (Wolters Kluwer Health | Lippincott Williams & Wilkins, 2017-09)
      Although efficacy of 36 months isoniazid preventive therapy (IPT) among HIV-positive individuals has been proven in trial settings, outcome, tolerance, and adherence have rarely been evaluated in real-life settings.This is a prospective observational cohort study conducted in 2 primary care rural clinics in Swaziland.After negative tuberculosis symptom screening, patients either with the positive tuberculin skin test (TST) or after tuberculosis treatment were initiated on IPT for 144 weeks. In addition to routine clinic visits, adherence was assessed every semester.Of 288 eligible patients, 2 patients never started IPT (1 refusal, 1 contraindication), and 253 (87.8%), 234 (81.3%), and 228 (79.2%) were still on IPT after 48, 96, and 144 weeks, respectively (chiP = .01). Of 41 patients who interrupted IPT before 144 weeks, 21 defaulted (of which 17 also defaulted HIV care); 16 stopped because of adverse drug reactions; 2 were discontinued by clinicians' mistake and 1 because of TB symptoms. Five patients (1.7%) died of causes not related to IPT, 5 (1.7%) developed TB of which 2 were isoniazid-resistant, and 9 (3.1%) were transferred to another clinic. As an indicator of adherence, isoniazid could be detected in the urine during 86.3% (302/350) and 73.6% (248/337) of patient visits in the 2 clinics, respectively (chiP < .001).The routine implementation of IPT 36 months was feasible and good patient outcomes were achieved, with low TB incidence, good tolerance, and sustained adherence.
    • Advances in imaging chest tuberculosis: blurring of differences between children and adults

      Andronikou, S; Vanhoenacker, F M; De Backer, A I; Medecins Sans Frontiers, Amsterdam, The Netherlands; Department of Radiology, University of Cape Town, Cape Town, South Africa; Department of Radiology, Sint-Maarten Hospital, Duffel-Mechelen, Belgium; University Hospital Antwerp, Edegem, Belgium; Department of Radiology, Sint-Lucas Hospital, Ghent, Belgium; (Elsevier, 2009-12-01)
      This article reviews the ongoing role of imaging in the diagnosis of tuberculosis (TB) and its complications. A modern imaging classification of TB, taking into account both adults and children and the blurring of differences in the presentation patterns, must be absorbed into daily practice. Clinicians must not only be familiar with imaging features of TB but also become expert at detecting these when radiologists are unavailable. Communication between radiologists and clinicians with regard to local constraints, patterns of disease, human immunodeficiency virus (HIV) coinfection rates, and imaging parameters relevant for management (especially in drug resistance programs) is paramount for making an impact with imaging, and preserving clinician confidence. Recognition of special imaging, anatomic and vulnerability differences between children and adults is more important than trying to define patterns of disease exclusive to children.
    • Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral and Second Line Anti-TB Treatment in Mumbai, India.

      Isaakidis, P; Varghese, B; Mansoor, H; Cox, H S; Ladomirska, J; Saranchuk, P; Da Silva, E; Khan, S; Paryani, R; Udwadia, Z; et al. (PLoS, 2012-07)
      Significant adverse events (AE) have been reported in patients receiving medications for multidrug- and extensively-drug-resistant tuberculosis (MDR-TB & XDR-TB). However, there is little prospective data on AE in MDR- or XDR-TB/HIV co-infected patients on antituberculosis and antiretroviral therapy (ART) in programmatic settings.
    • 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.
    • Alarming Levels of Drug-Resistant Tuberculosis in HIV-Infected Patients in Metropolitan Mumbai, India

      Isaakidis, P; Das, M; Kumar, A M V; Peskett, C; Khetarpal, M; Bamne, A; Adsul, B; Manglani, M; Sachdeva, K S; Parmar, M; et al. (Public Library of Science, 2014-10-21)
      Drug-resistant tuberculosis (DR-TB) is a looming threat to tuberculosis control in India. However, no countrywide prevalence data are available. The burden of DR-TB in HIV-co-infected patients is likewise unknown. Undiagnosed and untreated DR-TB among HIV-infected patients is a major cause of mortality and morbidity. We aimed to assess the prevalence of DR-TB (defined as resistance to any anti-TB drug) in patients attending public antiretroviral treatment (ART) centers in greater metropolitan Mumbai, India.
    • Alternative sputum collection methods for diagnosis of childhood intrathoracic tuberculosis: a systematic literature review

      Ioos, V; Cordel, H; Bonnet, M (The BMJ, 2018-08-20)
      Objective We aimed to measure the prevalence and incidence of latent tuberculosis infection (LTBI) and tuberculosis (TB) disease in children in close contact with patients with drug-resistant TB (DR-TB) in a country with high DR-TB prevalence. Design and setting This is a prospective cohort study of paediatric contacts of adult patients with pulmonary DR-TB in Armenia. Children were screened using tuberculin skin test, interferon-gamma release assay and chest X-ray at the initial consultation, and were reassessed every 3–6 months for a period of 24 months. Children did not receive preventive treatment. Main outcome measures Prevalence and incidence of LTBI and TB disease; factors associated with prevalent LTBI. Results At initial evaluation, 3 of the 150 children included were diagnosed with TB disease (2.0%). The prevalence of LTBI was 58.7%. The incidence of LTBI was 19.9 per 100 children per year, and was especially high during the first 6 months of follow-up (33.3 per 100 children per year). No additional cases with incident disease were diagnosed during follow-up. After adjustment, prevalent LTBI was significantly associated with the child’s age, sleeping in the same house, higher household density, the index case’s age, positive smear result and presence of lung cavities. Conclusions Children in close contact with patients with DR-TB or in contact with very contagious patients had an increased risk of prevalent LTBI. Although none of the children developed TB disease during a 2-year follow-up period, screening for symptoms of TB disease, based on the prevalence of disease at recruitment, together with follow-up and repeated testing of non-infected contacts, is highly recommended in paediatric contacts of patients with DR-TB.
    • Alternative sputum collection methods for diagnosis of childhood intrathoracic tuberculosis: a systematic literature review

      Ioos, V; Cordel, H; Bonnet, M (BMJ Journals, 2018-08-20)
      Diagnosis of intrathoracic tuberculosis (ITB) is limited in children partly by their difficulty to produce sputum specimen.
    • Ambulatory Multi-Drug Resistant Tuberculosis Treatment Outcomes in a Cohort of HIV-Infected Patients in a Slum Setting in Mumbai, India.

      Isaakidis, P; Cox, H S; Varghese, B; Montaldo, C; Da Silva, E; Mansoor, H; Ladomirska, J; Sotgiu, G; Migliori, G B; Pontali, E; et al. (2011-12)
      India carries one quarter of the global burden of multi-drug resistant TB (MDR-TB) and has an estimated 2.5 million people living with HIV. Despite this reality, provision of treatment for MDR-TB is extremely limited, particularly for HIV-infected individuals. Médecins Sans Frontières (MSF) has been treating HIV-infected MDR-TB patients in Mumbai since May 2007. This is the first report of treatment outcomes among HIV-infected MDR-TB patients in India.
    • 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.
    • Are sputum samples of retreatment tuberculosis reaching the reference laboratories? A 9-year audit in Tanzania

      Kilale, A M; Ngowi, B J; Mfinanga, G S; Egwaga, S; Doulla, B; Kumar, A M V; Khogali, M; van Griensven, J; Harries, A D; Zachariah, R; et al. (2013-06-21)
    • Are tuberculosis patients in a tertiary care hospital in Hyderabad, India being managed according to national guidelines?

      Kondapaka, K K; Prasad, S V; Satyanarayana, S; Kandi, S; Zachariah, R; Harries, A D; Nagaraja, S B; Tetali, S; Anchala, R; Kannuri, N K; et al. (Public Library of Science (PLoS), 2012-01-17)
      A tertiary health care facility (Government General and Chest hospital) in Hyderabad, India.
    • Assessing and improving data quality from community health workers: a successful intervention in Neno, Malawi

      Admon, A J; Bazile, J; Makungwa, H; Chingoli, M A; Hirschhorn, L R; Peckarsky, M; Rigodon, J; Herce, M; Chingoli, F; Malani, P N; et al. (International Union Against TB and Lung Disease, 2013-03)
    • Barriers and solutions to finding rifampicin-resistant tuberculosis cases in older children and adolescents

      Mohr-Holland, E; Apolisi, I; Reuter, A; de Azevedo, V; Hill, J; Matthee, S; Seddon, JA; Isaakidis, P; Furin, J; Trivino-Duran, L (International Union Against Tuberculosis and Lung Disease, 2019-12-21)
      Little is known about the barriers to post-exposure management of rifampicin-resistant tuberculosis (RR-TB) in older children and adolescents. We report on implementation lessons from a pilot programme targeting household-exposed individuals aged 6–18 years in Khayelitsha, South Africa. Barriers included misperceptions regarding risk of exposure, multiple research and implementation stakeholders, additional workload for an overburdened healthcare system, logistical issues faced by families, and insufficient human and financial resources. Solutions to these barriers are possible, but creativity and persistence are required. Our experience can guide others looking to roll-out care for children and adolescents exposed to RR-TB.