• Calling tuberculosis a social disease--an excuse for complacency?

      Isaakidis, P; Smith, S; Majumdar, S; Furin, J; Reid, T (Elsevier, 2014-09-20)
    • Can follow-up examination of tuberculosis patients be simplified? A study in Chhattisgarh, India

      Kundu, D; M V Kumar, A; Satyanarayana, S; Dewan, P K; Achuthan Nair, S; Khaparde, K; Nayak, P; Van den Bergh, R; Manzi, M; Enarson, D A; et al. (Public Library of Science, 2012-12-05)
      Each follow-up during the course of tuberculosis treatment currently requires two sputum examinations. However, the incremental yield of the second sputum sample during follow-up of different types of tuberculosis patients has never been determined precisely.
    • 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.
    • Challenges and controversies in childhood tuberculosis

      Reuter, A; Hughes, J; Furin, J (Elsevier, 2019-09-14)
      Children bear a substantial burden of suffering when it comes to tuberculosis. Ironically, they are often left out of the scientific and public health advances that have led to important improvements in tuberculosis diagnosis, treatment, and prevention over the past decade. This Series paper describes some of the challenges and controversies in paediatric tuberculosis, including the epidemiology and treatment of tuberculosis in children. Two areas in which substantial challenges and controversies exist (ie, diagnosis and prevention) are explored in more detail. This Series paper also offers possible solutions for including children in all efforts to end tuberculosis, with a focus on ensuring that the proper financial and human resources are in place to best serve children exposed to, infected with, and sick from all forms of tuberculosis.
    • Changes in Escherichia coli resistance to co-trimoxazole in tuberculosis patients and in relation to co-trimoxazole prophylaxis in Thyolo, Malawi.

      Zachariah, R; Harries, A D; Spielmann M P; Arendt, V; Nchingula, D; Mwenda, R; Courteille, O; Kirpach, P; Mwale, B; Salaniponi, F M L; et al. (Elsevier, 2008-01-31)
      In Thyolo district, Malawi, an operational research study is being conducted on the efficacy and feasibility of co-trimoxazole prophylaxis in preventing deaths in HIV-positive patients with tuberculosis (TB). A series of cross-sectional studies were carried out in 1999 and 2001 to determine (i) whether faecal Escherichia coli resistance to co-trimoxazole in TB patients changed with time, and (ii) whether the resistance pattern was different in HIV-positive TB patients who were taking co-trimoxazole prophylaxis. Co-trimoxazole resistance among E. coli isolates in TB patients at the time of registration was 60% in 1999 and 77% in 2001 (P < 0.01). Resistance was 89% among HIV-infected TB patients (receiving cotrimoxazole), while in HIV-negative patients (receiving anti-TB therapy alone) it was 62% (P < 0.001). The study shows a significant increase of E. coli resistance to co-trimoxazole in TB patients which is particularly prominent in HIV-infected patients on co-trimoxazole prophylaxis. Since a high degree of plasmid-mediated transfer of resistance exists between E. coli and the Salmonella species, these findings could herald limitations on the short- and long-term benefits to be expected from the use of co-trimoxazole prophylaxis in preventing non-typhoid Salmonella bacteraemia and enteritis in HIV-infected TB patients in Malawi.
    • Characteristics and outcomes of tuberculosis patients who fail to smear convert at two months in Sri Lanka

      Jayakody, W; Harries, A D; Malhotra, S; de Alwis, S; Samaraweera, S; Pallewatta, N (2013-03)
    • Characteristics and treatment outcomes of tuberculosis retreatment cases in three regional hospitals, Uganda

      Nakanwagi-Mukwaya, A; Reid, A J; Fujiwara, P I; Mugabe, F; Kosgei, R J; Tayler-Smith, K; Kizito, W; Joloba, M (2013-06)
    • Characteristics of drug-resistant tuberculosis in Abkhazia (Georgia), a high-prevalence area in Eastern Europe

      Pardini, M; Niemann, S; Varaine, F; Iona, E; Meacci, F; Orrù, G; Yesilkaya, H; Jarosz, T; Andrew, P; Barer, M; et al. (2009-06-18)
      Although multidrug-resistant (MDR) tuberculosis (TB) is a major public health problem in Eastern Europe, the factors contributing to emergence, spread and containment of MDR-TB are not well defined. Here, we analysed the characteristics of drug-resistant TB in a cross-sectional study in Abkhazia (Georgia) between 2003 and 2005, where standard short-course chemotherapy is supplemented with individualized drug-resistance therapy. Drug susceptibility testing (DST) and molecular typing were carried out for Mycobacterium tuberculosis complex strains from consecutive smear-positive TB patients. Out of 366 patients, 60.4% were resistant to any first-line drugs and 21% had MDR-TB. Overall, 25% of all strains belong to the Beijing genotype, which was found to be strongly associated with the risk of MDR-TB (OR 25.9, 95% CI 10.2-66.0) and transmission (OR 2.8, 95% CI 1.6-5.0). One dominant MDR Beijing clone represents 23% of all MDR-TB cases. The level of MDR-TB did not decline during the study period, coinciding with increasing levels of MDR Beijing strains among previously treated cases. Standard chemotherapy plus individualized drug-resistance therapy, guided by conventional DST, might be not sufficient to control MDR-TB in Eastern Europe in light of the spread of "highly transmissible" MDR Beijing strains circulating in the community.
    • Clinical Access to Bedaquiline Programme for the treatment of drug-resistant tuberculosis

      Conradie, F; Meintjes, G; Hughes, J; Maartens, G; Ferreira, H; Siwendu, S; Master, I; Ndjeka, N (Health & Medical Publishing Group, 2014-03-26)
      While clinical disease caused by drug-sensitive Mycobacterium tuberculosis (MTB) can usually be treated successfully, clinical disease caused by drug-insensitive MTB is associated with a poorer prognosis. In December 2012, a new drug, bedaquiline, was approved by the US Food and Drug Administration. This article documents the process whereby the National Department of Health, Right to Care and Médecins Sans Frontières obtained access to this medication for South Africans who might benefit from subsequent implementation of the Clinical Access to Bedaquiline Programme
    • Coadministration of lopinavir/ritonavir and rifampicin in HIV and tuberculosis co-infected adults in South Africa

      Murphy, R A; Marconi, V C; Gandhi, R T; Kuritzkes, D R; Sunpath, H; Medical Unit, Médecins Sans Frontières/Doctors Without Borders, New York, New York, United States of America (Public Library of Science, 2012-09-28)
      In HIV-infected patients receiving rifampicin-based treatment for tuberculosis (TB), the dosage of lopinavir/ritonavir (LPV/r) is adjusted to prevent sub-therapeutic lopinavir concentrations. In this setting, South African clinicians were advised to administer super-boosted LPV/r (400 mg/400 mg) twice daily, instead of standard dosed LPV/r (400 mg/100 mg) twice daily. We sought to determine--in routine practice--the tolerability and HIV treatment outcomes associated with super-boosted LPV/r compared to unadjusted LPV/r in combination with rifampicin-based TB treatment.
    • Community Knowledge, Attitudes and Practices in Relation to Tuberculosis in Cameroon

      Kwedi Nolna, S; Kammogne, ID; Ndzinga, R; Afanda, B; Ntonè, R; Boum, Y; Nolna, D (International Union Against Tuberculosis and Lung Disease, 2016-09-01)
      With 15 080 new cases in 2013, Cameroon is a country with high tuberculosis (TB) incidence and prevalence. Understanding the community's knowledge, attitude and practice (KAP) about TB is key to TB control in such endemic settings.
    • Compassionate Use of New Drugs in Children and Adolescents with Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis: Early Experiences and Challenges

      Tadolini, M; Garcia-Prats, AJ; D'Ambrosio, L; Hewison, C; Centis, R; Schaaf, HS; Marais, BJ; Ferreira, H; Caminero, JA; Jonckheere, S; et al. (European Respiratory Society, 2016-06-23)
    • 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.
    • The Contribution of a Non-Governmental Organisation's Community Based Tuberculosis Care Programme to Case Finding in Myanmar: Trend Over Time

      Maung, HM; Saw, S; Isaakidis, P; Khogali, M; Reid, A; Hoa, NB; Zaw, KK; Thein, S; Aung, ST (BioMed Central, 2017-04-03)
      It is estimated that the standard, passive case finding (PCF) strategy for detecting cases of tuberculosis (TB) in Myanmar has not been successful: 26% of cases are missing. Therefore, alternative strategies, such as active case finding (ACF) by community volunteers, have been initiated since 2011. This study aimed to assess the contribution of a Community Based TB Care Programme (CBTC) by local non-government organizations (NGOs) to TB case finding in Myanmar over 4 years.
    • Convergence of a Diabetes Mellitus, Protein Energy Malnutrition, and TB Epidemic: the Neglected Elderly Population

      Menon, S; Rossi, R; Nshimyumukiza, L; Wusiman, A; Zdraveska, N; Eldin, MS (BioMed Central, 2016-07-26)
      On a global scale, nearly two billion persons are infected with Mycobacterium tuberculosis. From this vast reservoir of latent tuberculosis (TB) infection, a substantial number will develop active TB during their lifetime, with some being able to transmit TB or Multi-drug- resistant (MDR) TB to others. There is clinical evidence pointing to a higher prevalence of infectious diseases including TB among individuals with Diabetes Mellitus (DM). Furthermore, ageing and diabetes mellitus may further aggravate protein-energy malnutrition (PEM), which in turn impairs T-lymphocyte mediated immunologic defenses, thereby increasing the risk of developing active TB and compromising TB treatment. This article aims to a) highlight synergistic mechanisms associated with immunosenescence, DM and PEM in relation to the development of active TB and b) identify nutritional, clinical and epidemiological research gaps.
    • Cost Per Patient of Treatment for Rifampicin-Resistant Tuberculosis in a Community-Based Programme in Khayelitsha, South Africa

      Cox, H; Ramma, L; Wilkinson, L; Azevedo, V; Sinanovic, E (Wiley-Blackwell, 2015-10)
      The high cost of rifampicin-resistant tuberculosis (RR-TB) treatment hinders treatment access. South Africa has a high RR-TB burden, and national policy outlines decentralisation to improve access and reduce costs. We analysed health system costs associated with RR-TB treatment by drug resistance profile and treatment outcome in a decentralised programme.
    • 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.
    • Countries are out of step with international recommendations for tuberculosis testing, treatment, and care: Findings from a 29-country survey of policy adoption and implementation

      Saran, K; Masini, T; Chikwanha, I; Paton, G; Scourse, R; Kahn, P; Sahu, S; Perrin, C; Ditiu, L; Lynch, S (bioRxiv, 2019-02-01)
      Background: Tuberculosis (TB) poses a global health crisis requiring robust international and country-level action. Adopting and implementing TB policies from the World Health Organization (WHO) is essential to meeting global targets for reducing TB burden. However, many high TB burden countries lag in implementing WHO recommendations. Assessing the progress of implementation at national level can identify key gaps that must be addressed to expand and improve TB care. Methods: In 2016/2017, Médecins Sans Frontières and the Stop TB Partnership conducted a survey on adoption and implementation of 47 WHO TB policies in the national TB programs of 29 countries. Here we analyze a subset of 23 key policies in diagnosis, models of care, treatment, prevention, and drug regulation to provide a snapshot of national TB policy adoption and implementation. We examine progress since an analogous 2015 survey of 23 of the same countries. Results: At the time of the survey, many countries had not yet aligned their national guidelines with all WHO recommendations, although some progress was seen since 2015. For diagnosis, about half of surveyed countries had adopted the WHO-recommended initial rapid test (Xpert MTB/RIF). A majority of countries had adopted decentralized models of care, although one-third of them still required hospitalization for drug-resistant (DR-)TB. Recommended use of the newer drugs bedaquiline (registered in only 6 high-burden TB countries) and delamanid (not registered in any high-burden country) was adopted by 23 and 18 countries, respectively, but short-course (9-month) and newer pediatric regimens by only 13 and 14 countries, respectively. Guidelines in all countries included preventive treatment of latent TB infection for child TB contacts and people living with HIV/AIDS, but only four extended this to adult contacts. Conclusion: To reach global TB targets, greater political will is needed to rapidly adopt and implement internationally recognized care guidelines.
    • Culture conversion at six months in patients receiving delamanid-containing regimens for the treatment of multidrug-resistant tuberculosis.

      Seung, KJ; Khan, P; Franke, MF; Ahmed, S; Aiylchiev, S; Alam, M; Putri, FA; Bastard, M; Docteur, W; Gottlieb, G; et al. (Oxford University Press, 2019-11-02)
      Delamanid should be effective against highly resistant strains of Mycobacteriumtuberculosis, but uptake has been slow globally. In the endTB (expand new drug markets for TB) Observational Study, which enrolled a large, heterogeneous cohorts of patients receiving delamanid as part of a multidrug regimen, 80% of participants experienced sputum culture conversion within 6 months.