• The Need to Accelerate Access to New Drugs for Multidrug-resistant Tuberculosis

      Cox, H; Furin, J J; Mitnick, C D; Daniels, C; Cox, V; Goemaere, E (World Health Organization, 2015-07-01)
      Approximately half a million people are thought to develop multidrug-resistant tuberculosis annually. Barely 20% of these people currently receive recommended treatment and only about 10% are successfully treated. Poor access to treatment is probably driving the current epidemic, via ongoing transmission. Treatment scale-up is hampered by current treatment regimens, which are lengthy, expensive, poorly tolerated and difficult to administer in the settings where most patients reside. Although new drugs provide an opportunity to improve treatment regimens, current and planned clinical trials hold little promise for developing regimens that will facilitate prompt treatment scale-up. In this article we argue that clinical trials, while necessary, should be complemented by timely, large-scale, operational research that will provide programmatic data on the use of new drugs and regimens while simultaneously improving access to life-saving treatment. Perceived risks - such as the rapid development of resistance to new drugs - need to be balanced against the high levels of mortality and transmission that will otherwise persist. Doubling access to treatment and increasing treatment success could save approximately a million lives over the next decade.
    • Nevirapine or efavirenz for tuberculosis and HIV coinfected patients: exposure and virological failure relationship

      Bhatt, N B; Baudin, E; Meggi, B; da Silva, C; Barrail-Tran, A; Furlan, V; Grinsztejn, B; Bonnet, M; Taburet, A-M (Oxford University Press, 2014-09-18)
      We describe nevirapine and efavirenz exposure on and off tuberculosis treatment and consequences for virological efficacy and tolerance in patients included in the ANRS 12146/12214-CARINEMO trial.
    • New and Repurposed Drugs for Pediatric Multidrug-Resistant Tuberculosis. Practice-based Recommendations

      Harausz, E; Garcia-Prats, A; Seddon, J; Schaaf, H; Hesseling, A; Achar, J; Bernheimer, J; Cruz, A; D'Ambrosio, L; Detjen, A; et al. (American Thoracic Society, 2017-05-15)
      It is estimated that 33,000 children develop multidrug-resistant tuberculosis (MDR-TB) each year. In spite of these numbers, children and adolescents have limited access to the new and repurposed MDR-TB drugs. There is also little clinical guidance for the use of these drugs and for the shorter MDR-TB regimen in the pediatric population. This is despite the fact that these drugs and regimens are associated with improved interim outcomes and acceptable safety profiles in adults. This review fills a gap in the pediatric MDR-TB literature by providing practice-based recommendations for the use of the new (delamanid and bedaquiline) and repurposed (linezolid and clofazimine) MDR-TB drugs and the new shorter MDR-TB regimen in children and adolescents.
    • New approaches to filling the gap in tuberculosis drug discovery.

      Casenghi, M; Cole, S; Nathan, C F; Médecins Sans Frontières, Campaign for Access to Essential Medicines, Geneva. martina.casenghi@geneva.msf.org (Public Library of Science, 2007-11-06)
    • New diagnostic tests for tuberculosis in southern countries: from theory to practice in Southern countries

      Bonnet, M; Epicentre, Médecins-Sans-Frontières, Geneva, Switzerland (Elservier, 2011-12)
      Tuberculosis (TB) is responsible of 1.7 millions of deaths per year worldwide. In high burden countries sputum smear-microscopy diagnoses only half of the cases of pulmonary TB. It is unlikely that a new test will replace smear-microscopy in peripheral services in the short term.
    • New Diagnostics for Tuberculosis: Fulfilling Patient Needs First

      Lemaire, J-F; Casenghi, M; Médecins Sans Frontières Campaign for Access to Essential Medicines, Switzerland; (2010-10-25)
      An effective tuberculosis (TB) control programme requires early diagnosis and immediate initiation of treatment. Any delays in diagnosing TB not only impair a patient's prognosis, but also increase the risks of transmitting the disease within the community. Unfortunately, the most recent TB diagnostic tools still depend on high-infrastructure laboratories, making them poorly adapted for use in resource-limited settings. Additionally, existing tests show poor performance in diagnosing TB in children, people living with HIV/AIDS, and extrapulmonary forms of the disease. As a consequence, TB patients are still to date left with either fair access to poor diagnostics or poor access to fair diagnostics.
    • New opportunities in tuberculosis prevention: implications for people living with HIV.

      Gonzalez Fernandez, L; Casas, EC; Singh, S; Churchyard, GJ; Brigden, G; Gotuzzo, E; Vandevelde, W; Sahu, S; Ahmedov, S; Kamarulzaman, A; et al. (Wiley Open Access, 2020-01-01)
      INTRODUCTION: Tuberculosis (TB) is a leading cause of mortality among people living with HIV (PLHIV). An invigorated global END TB Strategy seeks to increase efforts in scaling up TB preventive therapy (TPT) as a central intervention for HIV programmes in an effort to contribute to a 90% reduction in TB incidence and 95% reduction in mortality by 2035. TPT in PLHIV should be part of a comprehensive approach to reduce TB transmission, illness and death that also includes TB active case-finding and prompt, effective and timely initiation of anti-TB therapy among PLHIV. However, the use and implementation of preventive strategies has remained deplorably inadequate and today TB prevention among PLHIV has become an urgent priority globally. DISCUSSION: We present a summary of the current and novel TPT regimens, including current evidence of use with antiretroviral regimens (ART). We review challenges and opportunities to scale-up TB prevention within HIV programmes, including the use of differentiated care approaches and demand creation for effective TB/HIV services delivery. TB preventive vaccines and diagnostics, including optimal algorithms, while important topics, are outside of the focus of this commentary. CONCLUSIONS: A number of new tools and strategies to make TPT a standard of care in HIV programmes have become available. The new TPT regimens are safe and effective and can be used with current ART, with attention being paid to potential drug-drug interactions between rifamycins and some classes of antiretrovirals. More research and development is needed to optimize TPT for small children, pregnant women and drug-resistant TB (DR-TB). Effective programmatic scale-up can be supported through context-adapted demand creation strategies and the inclusion of TPT in client-centred services, such as differentiated service delivery (DSD) models. Robust collaboration between the HIV and TB programmes represents a unique opportunity to ensure that TB, a preventable and curable condition, is no longer the number one cause of death in PLHIV.
    • Non-disclosure of tuberculosis diagnosis by patients to their household members in south western Uganda

      Nyangoma, M; Bajunirwe, F; Atwine, D (Public Library of Science, 2020-01-24)
      BACKGROUND: Tuberculosis (TB) non-disclosure by adult patients to all household members is a setback to TB control efforts. It reduces the likelihood that household contacts will seek early TB screening, initiation on preventive or curative treatment, but also hinders the implementation of infection controls and home-based directly observed treatment. Therefore, the purpose of this study was to determine the level of TB non-disclosure, its predictors and the effects of disclosure among adult TB patients in Uganda. METHODS: We conducted a cross-sectional study at a large regional referral hospital in Mbarara, south-western Uganda. Questionnaires were administered to collect patients' sociodemographic and their TB disclosure data. Non-disclosure was considered if a patient did not reveal their TB diagnosis to all household members within 2 weeks post-treatment initiation. Univariate and multivariate logistic regression models were fitted for predictors of non-disclosure. RESULTS: We enrolled 62 patients, 74% males, mean age of 32 years, and median of five people per household. Non-disclosure rate was 30.6%. Post-disclosure experiences were positive in 98.3% of patients, while negative experiences suggestive of severe stigma occurred in 12.3% of patients. Being female (OR 6.5, 95% CI: 1.4-29.3) and belonging to Muslim faith (OR 12.4, 95% CI: 1.42-109.1) were significantly associated with TB non-disclosure to household members. CONCLUSIONS: There is a high rate of TB non-disclosure to all household members by adult patients in rural Uganda, particularly among women and muslim patients. Interventions enhancing TB disclosure at household level while minimizing negative effects of stigma should be developed and prioritized.
    • 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.