• Off-Label Use of Bedaquiline in Children and Adolescents with Multidrug-Resistant Tuberculosis

      Achar, J; Hewison, C; Cavalheiro, AP; Skrahina, A; Cajazeiro, J; Nargiza, P; Herboczek, K; Rajabov, A; Hughes, J; Ferlazzo, G; et al. (Centers for Disease Control and Prevention, 2017-10)
      We describe 27 children and adolescents <18 years of age who received bedaquiline during treatment for multidrug-resistant tuberculosis. We report good treatment responses and no cessation attributable to adverse effects. Bedaquiline could be considered for use with this age group for multidrug-resistant tuberculosis when treatment options are limited.
    • Operational challenges in managing Isoniazid Preventive Therapy in child contacts: A high-burden setting perspective.

      van Wyk, S S; Reid, A J; Mandalakas, A M; Enarson, D A; Beyers, N; Morrison, J; Hesseling, A C (2011-07-08)
      ABSTRACT: BACKGROUND: The study was conducted at a high TB-HIV burden primary health community clinic in Cape Town, South Africa. We describe the management of children under five years of age in household contact with a smear and/or culture-positive adult TB case. METHODS: This study was a record review of routinely-collected programme data. RESULTS: A total of 1094 adult TB case folders were reviewed. From all identified contacts, 149 children should have received IPT based on local guidelines; in only 2/149 IPT was initiated. Management of child contacts of sputum smear and/or culture-positive compared to sputum-negative TB patients were similar. CONCLUSIONS: IPT delivery to children remains an operational challenge, especially in high TB-HIV burden communities. A tool to improve IPT management and targeting sputum smear and/or culture-positive TB child contacts may overcome some of these challenges and should be developed and piloted in such settings.
    • Operational research leading to rapid national policy change: tuberculosis-diabetes collaboration in India

      Kumar, A M V; Satyanarayana, S; Wilson, N C; Chadha, S S; Gupta, D; Nair, S; Zachariah, R; Kapur, A; Harries, A D (International Union Against Tuberculosis and Lung Disease, 2014-06-21)
    • Operational research within a Global Fund supported tuberculosis project in India: why, how and its contribution towards change in policy and practice.

      Sagili, KD; Satyanarayana, S; Chadha, SS; Wilson, NC; Kumar, AMV; Moonan, PK; Oeltmann, JE; Chadha, VK; Nagaraja, SB; Ghosh, S; et al. (Taylor & Francis, 2018-02)
      BACKGROUND: The Global Fund encourages operational research (OR) in all its grants; however very few reports describe this aspect. In India, Project Axshya was supported by a Global Fund grant to improve the reach and visibility of the government Tuberculosis (TB) services among marginalised and vulnerable communities. OR was incorporated to build research capacity of professionals working with the national TB programme and to generate evidence to inform policies and practices. OBJECTIVES: To describe how Project Axshya facilitated building OR capacity within the country, helped in addressing several TB control priority research questions, documented project activities and their outcomes, and influenced policy and practice. METHODS: From September 2010 to September 2016, three key OR-related activities were implemented. First, practical output-oriented modular training courses were conducted (n = 3) to build research capacity of personnel involved in the TB programme, co-facilitated by The Union, in collaboration with the national TB programme, WHO country office and CDC, Atlanta. Second, two large-scale Knowledge, Attitude and Practice (KAP) surveys were conducted at baseline and mid-project to assess the changes pertaining to TB knowledge, attitudes and practices among the general population, TB patients and health care providers over the project period. Third, studies were conducted to describe the project's core activities and outcomes. RESULTS: In the training courses, 44 participant teams were supported to develop research protocols on topics of national priority, resulting in 28 peer-reviewed scientific publications. The KAP surveys and description of project activities resulted in 14 peer-reviewed publications. Of the published papers at least 12 have influenced change in policy or practice. CONCLUSIONS: OR within a Global Fund supported TB project has resulted in building OR capacity, facilitating research in areas of national priority and influencing policy and practice. We believe this experience will provide guidance for undertaking OR in Global Fund projects.
    • Outcome of Children with Presumptive Tuberculosis in Mbarara, Rural Uganda

      Bonnet, M; Nansumba, M; Bastard, M; Orikiriza, P; Kyomugasho, N; Nansera, D; Boum, Y; de Beaudrap, P; Kiwanuka, J; Kumbakumba, E (Wolters Kluwer Health | Lippincott Williams & Wilkins, 2017-08-02)
      Mortality among children with presumptive tuberculosis (TB) empiric TB treatment can be high. We describe the predictors of death among children with presumptive TB, and the relation between treatment and mortality.
    • Outcomes after chemotherapy with WHO category II regimen in a population with high prevalence of drug resistant tuberculosis.

      Matthys, F; Rigouts, L; Sizaire, V; Vezhnina, N; Lecoq, M; Golubeva, V; Portaels, F; Van der Stuyft, P; Kimerling, M; Epidemiological and Disease Control Unit, Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium. fmatthys@itg.be (PLoS, 2009-12)
      Standard short course chemotherapy is recommended by the World Health Organization to control tuberculosis worldwide. However, in settings with high drug resistance, first line standard regimens are linked with high treatment failure. We evaluated treatment outcomes after standardized chemotherapy with the WHO recommended category II retreatment regimen in a prison with a high prevalence of drug resistant tuberculosis (TB). A cohort of 233 culture positive TB patients was followed through smear microscopy, culture, drug susceptibility testing and DNA fingerprinting at baseline, after 3 months and at the end of treatment. Overall 172 patients (74%) became culture negative, while 43 (18%) remained positive at the end of treatment. Among those 43 cases, 58% of failures were determined to be due to treatment with an inadequate drug regimen and 42% to either an initial mixed infection or re-infection while under treatment. Overall, drug resistance amplification during treatment occurred in 3.4% of the patient cohort. This study demonstrates that treatment failure is linked to initial drug resistance, that amplification of drug resistance occurs, and that mixed infection and re-infection during standard treatment contribute to treatment failure in confined settings with high prevalence of drug resistance.
    • Outcomes From the First Multidrug-Resistant Tuberculosis Programme in Kenya

      Huerga, H; Bastard, M; Kamene, M; Wanjala, S; Arnold, A; Oucho, N; Chikwanha, I; Varaine, F (International Union Against Tuberculosis and Lung Disease, 2017-03-01)
      In March 2006, the first multidrug-resistant tuberculosis (MDR-TB) treatment programme was implemented in Kenya.
    • Outcomes in Adolescents Undergoing Treatment for Drug-Resistant Tuberculosis in Cape Town, South Africa, 2008-2013

      Moyo, S; Furin, J J; Hughes, J; Daniels, J; Snyman, L; Muller, O; Cox, V; Shroufi, A; Cox, H (Pediatric Infection Research Center, 2014-03-06)
    • Outcomes of Bedaquiline Treatment in Patients with Multidrug-Resistant Tuberculosis

      Mbuagbaw, L; Guglielmetti, L; Hewison, C; Bakare, N; Bastard, M; Caumes, E; Frechet-Jachym, M; Robert, J; Veziris, N; Khachatryan, N; et al. (Centers for Disease Control and Prevention, 2019-05-01)
      Bedaquiline is recommended by the World Health Organization for the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). We pooled data from 5 cohorts of patients treated with bedaquiline in France, Georgia, Armenia, and South Africa and in a multicountry study. The rate of culture conversion to negative at 6 months (by the end of 6 months of treatment) was 78% (95% CI 73.5%-81.9%), and the treatment success rate was 65.8% (95% CI 59.9%-71.3%). Death rate was 11.7% (95% CI 7.0%-19.1%). Up to 91.1% (95% CI 82.2%-95.8%) of the patients experienced >1 adverse event, and 11.2% (95% CI 5.0%-23.2%) experienced a serious adverse event. Lung cavitations were consistently associated with unfavorable outcomes. The use of bedaquiline in MDR and XDR TB treatment regimens appears to be effective and safe across different settings, although the certainty of evidence was assessed as very low.
    • Outcomes of HIV-infected versus HIV-non-infected patients treated for drug-resistance tuberculosis: Multicenter cohort study

      Bastard, M; Sanchez-Padilla, E; du Cros, P; Khamraev, AK; Parpieva, N; Tillyashaykov, M; Hayrapetyan, A; Kimenye, K; Khurkhumal, S; Dlamini, T; et al. (Public Library of Science, 2018-03-08)
      The emergence of resistance to anti-tuberculosis (DR-TB) drugs and the HIV epidemic represent a serious threat for reducing the global burden of TB. Although data on HIV-negative DR-TB treatment outcomes are well published, few data on DR-TB outcomes among HIV co-infected people is available despite the great public health importance.
    • Outcomes of tuberculosis patients who start antiretroviral therapy under routine programme conditions in Malawi

      Makombe, S D; Harries, A D; Yu, J K-L; Hochgesang, M; Mhango, E; Weigel, R; Pasulani, O; Fitzgerald, M; Schouten, E J; Libamba, E; et al. (2007-04-01)
      SETTING: Public sector facilities in Malawi providing antiretroviral therapy (ART) to human immunodeficiency virus (HIV) positive patients, including those with tuberculosis (TB). OBJECTIVES: To compare 6-month and 12-month cohort treatment outcomes of HIV-positive TB patients and HIV-positive non-TB patients treated with ART. DESIGN: Retrospective data collection using ART patient master cards and ART patient registers. RESULTS: Between July and September 2005, 7905 patients started ART, 6967 with a non-TB diagnosis and 938 with a diagnosis of active TB. 6-month cohort outcomes of non-TB and TB patients censored on 31 March 2006 showed significantly more TB patients alive and on ART (77%) compared with non-TB patients (71%) (P < 0.001). Between January and March 2005, 4580 patients started ART, 4179 with a non-TB diagnosis and 401 with a diagnosis of active TB. 12-month cohort outcomes of non-TB and TB patients censored on 31 March 2006 showed significantly more TB patients alive and on ART (74%) compared with non-TB patients (66%) (P < 0.001). Other outcomes of default and transfer out were also significantly less frequent in TB compared with non-TB patients. CONCLUSION: HIV-positive TB patients on ART in Malawi have generally good treatment outcomes, and more patients need to access this HIV treatment.
    • Overcoming Challenges in the Diagnosis, Prevention, and Treatment of Pediatric Drug-Resistant Tuberculosis

      Jonckheree, S; Furin, J (Taylor & Francis. We regret that this article is behind a paywall., 2017-03-28)
      Drug-resistant tuberculosis (DR-TB) is a growing global health threat and children are especially vulnerable to becoming infected and sick with DR-TB. There is a growing body of evidence on the optimal diagnosis, treatment and prevention of DR-TB in this vulnerable population. Areas covered: A comprehensive review of the literature on DR-TB in children was done using PubMed and Ovid databases up to 31 December 2016. Topic areas covered included diagnosis of DR-TB, treatment of DR-TB - including novel medications and regimens, prevention of DR-TB, community-based care, and stigma/discrimination. After presenting a case that highlights some of these challenges in each of these areas, for which we will propose mechanisms for overcoming them. Expert commentary: Overcoming the challenges facing children with DR-TB, requires a paradigm shift at multiple levels. The 'trickle down' approach to pediatric DR-TB has been woefully inadequate and it is essential that pediatric DR-TB - preventing it, diagnosing it, and treating it - be made a priority.
    • Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome after early initiation of antiretroviral therapy in a randomized clinical trial

      Laureillard, D; Marcy, O; Madec, Y; Chea, S; Chan, S; Borand, L; Fernandez, M; Prak, N; Kim, C; Dim, B; et al. (Lippincott Williams & Wilkins, 2013-10-23)
      To analyze cases of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in the CAMbodian Early versus Late Introduction of Antiretrovirals (CAMELIA) randomized trial designed to compare early (2 weeks) versus late (8 weeks) antiretroviral therapy (ART) initiation after tuberculosis treatment onset in Cambodia (NCT00226434).
    • "Paradoxical" immune-mediated reactions to Mycobacterium ulcerans during antibiotic treatment: a result of treatment success, not failure.

      O'Brien, D P; Robson, M E; Callan, P P; McDonald, A H; Barwon Health, Geelong, VIC, Australia. daniel.obrien@amsterdam.msf.org. (2009-11-16)
      We present the first clinical descriptions of immune-mediated paradoxical reactions to effective antibiotic treatment for Mycobacterium ulcerans infection, which result in clinical deterioration after initial improvement. Recognition of this phenomenon could prevent unnecessary changes to antibiotic regimens, and might obviate the need for, or reduce the extent of, further surgery. (MJA 2009; 191: 564-566).
    • Paragonimiasis in Tuberculosis Patients in Nagaland, India

      Das, M; Doleckova, K; Shenoy, R; Mahanta, J; Narain, K; Devi, KR; Konyak, T; Mansoor, H; Isaakidis, P (Co-Action Publishing, 2016-09-23)
      One of the infections that mimic tuberculosis (TB) is paragonimiasis (PRG), a foodborne parasitic disease caused by lung flukes of the genus Paragonimus. In the northeastern states of India, TB and PRG are endemic; however, PRG is rarely included in the differential diagnosis of TB.
    • Passive Versus Active Tuberculosis Case Finding and Isoniazid Preventive Therapy Among Household Contacts in a Rural District of Malawi.

      Zachariah, R; Spielmann M P; Harries, A D; Gomani, P; Graham, S; Bakali, E; Humblet, P; Operational Research (HIV/TB), Medical Department, Médecins sans Frontières-Brussels Operational Centre, Brussels, Belgium. zachariah@internet.lu (International Union Against TB and Lung Disease, 2003-11)
      SETTING: Thyolo district, rural Malawi. OBJECTIVES: To compare passive with active case finding among household contacts of smear-positive pulmonary tuberculosis (TB) patients for 1) TB case detection and 2) the proportion of child contacts aged under 6 years who are placed on isoniazid (INH) preventive therapy. DESIGN: Cross-sectional study. METHODS: Passive and active case finding was conducted among household contacts, and the uptake of INH preventive therapy in children was assessed. RESULTS: There were 189 index TB cases and 985 household contacts. Human immunodeficiency virus (HIV) prevalence among index cases was 69%. Prevalence of TB by passive case finding among 524 household contacts was 0.19% (191/100000), which was significantly lower than with active finding among 461 contacts (1.74%, 1735/100000, P = 0.01). Of 126 children in the passive cohort, 22 (17%) received INH, while in the active cohort 25 (22%) of 113 children received the drug. Transport costs associated with chest X-ray (CXR) screening were the major reason for low INH uptake. CONCLUSIONS: Where the majority of TB patients are HIV-positive, active case finding among household contacts yields nine times more TB cases and is an opportunity for reducing TB morbidity and mortality. The need for a CXR is an obstacle to the uptake of INH prophylaxis.
    • Patch-Testing for the Management of Hypersensitivity Reactions to Second-Line Anti-Tuberculosis Drugs: A Case Report

      Khan, S; Andries, A; Pherwani, A; Saranchuk, P; Isaakidis, P (BioMed Central (Springer Science), 2014-08-15)
      The second-line anti-tuberculosis drugs used in the treatment of multidrug-resistant tuberculosis often cause adverse events, especially in patients co-infected with the human immunodeficiency virus. Severe hypersensitivity reactions due to these drugs are rare and there is little published experience to guide their management.
    • Patients' Costs Associated With Seeking and Accessing Treatment for Drug-Resistant Tuberculosis in South Africa

      Ramma, L; Cox, H; Wilkinson, L; Foster, N; Cunnama, L; Vassall, A; Sinanovic, E (International Union Against TB and Lung Disease, 2015-12)
      South Africa is one of the world's 22 high tuberculosis (TB) burden countries, with the second highest number of notified rifampicin-resistant TB (R(R)-TB) and multidrug-resistant TB (MDR-TB) cases.
    • Performance of FASTPlaqueTB and a modified protocol in a high HIV prevalence community in South Africa.

      Trollip, A P; Albert, H; Mole, R; Marshall, T; van Cutsem, G; Coetzee, D; Biotec Laboratories South Africa Ltd, Cape Town, South Africa. andre.trollip@bioteclabs.co.za (2009-06)
      Modifications in the FASTPlaqueTB test protocol have resulted in an increase in the analytical limits of detection. This study investigated whether the performance of a modified prototype was able to increase the detection of smear-negative, culture-positive sputum samples as compared to the first generation FASTPlaqueTB test. Modifications to the FASTPlaqueTB did result in increased detection of smear-negative samples, but this was associated with a decrease in the specificity of the test. Before the FASTPlaqueTB can be considered as a viable replacement for smear microscopy and culture for the identification of tuberculosis, further work is required to resolve the performance issues identified in this study.