• 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.
    • A Bayesian Response-Adaptive Trial in Tuberculosis: The endTB Trial

      Cellamare, M; Ventz, S; Baudin, E; Mitnick, CD; Trippa, L (SAGE Publications, 2016-08-23)
      To evaluate the use of Bayesian adaptive randomization for clinical trials of new treatments for multidrug-resistant tuberculosis.
    • Bedaquiline and delamanid in combination for treatment of drug-resistant tuberculosis

      Mohr, E; Ferlazzo, G; Hewison, C; De Azevedo, V; Isaakidis, P (Elsevier, 2019-05-01)
      Here we report on the final outcomes for the cohort of 28 patients from Armenia, India, and South Africa who initiated regimens containing the combination of bedaquiline and delamanid from January to August, 2016, for the treatment of multidrug-resistant tuberculosis in our cohort study.1 The median duration on combination treatment was 12 months (interquartile range [IQR] 5·9–20·0); 17 (61%) of 28 patients received the combination for more than 6 months.
    • Bedaquiline overdose: A case report

      Telnov, O; Alvarez, V; Graglia, E; Molfino, L; du Cros, P; Rich, M (Elsevier, 2019-07)
      We present a case report describing outcomes in a 21 year old HIV-negative man who received treatment with bedaquiline. Due to error, dosage received comprised 4 pills of 100 mg every second day in the 60 days following the first two weeks of 4 pills of 100 mg every day. On detection, treatment was continued as per standard dosing of 200 mg given three times per week, with enhanced monitoring of ECG and liver function. The man was asymptomatic, with no signs of jaundice, abdominal pain, or abnormal heart rhythm. Toxic effects at this dosage were therefore not observed.
    • Bedaquiline overdose: A case report

      Telnov, O; Alvarez, V; Gragila, E; Molfino, L; du Cros, P; Rich, M (Elsevier, 2019-04-02)
      We present a case report describing outcomes in a 21 year old HIV-negative man who received treatment with bedaquiline. Due to error, dosage received comprised 4 pills of 100 mg every second day in the 60 days following the first two weeks of 4 pills of 100 mg every day. On detection, treatment was continued as per standard dosing of 200 mg given three times per week, with enhanced monitoring of ECG and liver function. The man was asymptomatic, with no signs of jaundice, abdominal pain, or abnormal heart rhythm. Toxic effects at this dosage were therefore not observed.
    • The Beijing genotype and drug resistant tuberculosis in the Aral Sea region of Central Asia.

      Cox, H; Kubica, T; Doshetov, D; Kebede, Y; Rüsch-Gerdess, S; Niemann, S; Médecins Sans Frontières, Aral Sea Area Programme, Uzbekistan and Turkmenistan Tashkent, Uzbekistan. h.cox2@pgrad.unimelb.edu.au (2005)
      BACKGROUND: After the collapse of the Soviet Union, dramatically increasing rates of tuberculosis and multidrug-resistant tuberculosis (MDR-TB) have been reported from several countries. This development has been mainly attributed to the widespread breakdown of TB control systems and declining socio-economic status. However, recent studies have raised concern that the Beijing genotype of Mycobacterium tuberculosis might be contributing to the epidemic through its widespread presence and potentially enhanced ability to acquire resistance. METHODS: A total of 397 M. tuberculosis strains from a cross sectional survey performed in the Aral Sea region in Uzbekistan and Turkmenistan have been analysed by drug susceptibility testing, IS6110 fingerprinting, and spoligotyping. RESULTS: Fifteen isolates showed mixed banding patterns indicating simultaneous infection with 2 strains. Among the remaining 382 strains, 152 (40%) were grouped in 42 clusters with identical fingerprint and spoligotype patterns. Overall, 50% of all isolates were Beijing genotype, with 55% of these strains appearing in clusters compared to 25% of non-Beijing strains. The percentage of Beijing strains increased with increasing drug resistance among both new and previously treated patients; 38% of fully-susceptible isolates were Beijing genotype, while 75% of MDR-TB strains were of the Beijing type. CONCLUSION: The Beijing genotype is a major cause of tuberculosis in this region, it is strongly associated with drug resistance, independent of previous tuberculosis treatment and may be strongly contributing to the transmission of MDR-TB. Further investigation around the consequences of Beijing genotype infection for both tuberculosis transmission and outcomes of standard short course chemotherapy are urgently needed.
    • Better Treatment of XDR Tuberculosis Needed in South Africa

      Cox, H; van Cutsem, G; Cox, V (Elsevier, 2014-08-16)
    • Beyond 'cure' and 'treatment success': quality of life of patients with multidrug-resistant tuberculosis

      Laxmeshwar, C; Stewart, A G; Dalal, A; Kumar, A M V; Kalaiselvi, S; Das, M; Gawde, N; Thi, S S; Isaakidis, P (International Union Against Tuberculosis and Lung Disease, 2019-01-01)
      Two drug-resistant tuberculosis (DR-TB) sites (MSF Clinic, Jupiter Hospital) in Mumbai, India.
    • Bleach sedimentation: an opportunity to optimize smear microscopy for tuberculosis diagnosis in settings of high prevalence of HIV

      Bonnet, M; Ramsay, A; Githui, W; Gagnidze, L; Varaine, F; Guerin, P J; Epicentre, Paris, France; Médecins Sans Frontières, Paris, France; Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Centre for Respiratory Diseases Research, Kenya Medical Research Institute, Nairobi, Kenya (Infectious Diseases Society of America, 2008-06-01)
      BACKGROUND: The purpose of the study was to evaluate the performance and feasibility of tuberculosis diagnosis by sputum microscopy after bleach sedimentation, compared with by conventional direct smear microscopy, in a setting of high prevalence of HIV. METHODS: In a community-based study in Kenya (a population in which 50% of individuals with tuberculosis are infected with HIV), individuals with suspected pulmonary tuberculosis submitted 3 sputum specimens during 2 consecutive days, which were examined by blind evaluation. Ziehl-Neelsen-stained smears were made of fresh specimens and of specimens that were processed with 3.5% household bleach followed by overnight sedimentation. Two different cutoffs for acid-fast bacilli (AFB) per 100 high-power fields (HPF) were used to define a positive smear: >10 AFB/100 HPF and 1 AFB/100 HPF. Four smear-positive case definitions, based on 1 or 2 positive smears with the 1 AFB or 10 AFB cutoff, were used. RESULTS: Of 1879 specimens from 644 patients, 363 (19.3%) and 460 (24.5%) were positive by bleach sedimentation microscopy, compared with 301 (16.0%) and 374 (19.9%) by direct smear microscopy, with use of the 10 AFB/100 HPF (P < .001) and 1 AFB/100 HPF (P < .001) cutoffs, respectively. Regardless of the case definition used, bleach sedimentation microscopy detected significantly more positive cases than did direct smear microscopy: 26.7% (172 of 644) versus 21.7% (140 of 644), respectively, with the case definition of 1 positive smear and the 1 AFB/100 HPF cutoff (P < .001), and 21.4% (138 of 644) versus 18.6% (120 of 644), respectively, with the case definition of 1 positive smear and the 10 AFB/100 HPF cutoff (P < .001). Inter- and intrareader reproducibility were favorable, with kappa coefficients of 0.83 and 0.91, respectively. Bleach sedimentation was relatively inexpensive and was not time consuming. CONCLUSIONS: Bleach sedimentation microscopy is an effective, simple method to improve the yield of smear microscopy in a setting of high prevalence of HIV. Further evaluation of this method, under operational conditions, is urgently needed to determine its potential as a tool for tuberculosis control.
    • Breast tuberculosis in men: A systematic review

      Quaglio, G; Pizzol, D; Bortolani, A; Manenti, F; Isaakidis, P; Putoto, G; Olliaro, PL (Public Library of Science, 2018-04-03)
      Breast tuberculosis in male is a rarely reported and poorly described condition.
    • Building clinical trials capacity for tuberculosis drugs in high-burden countries

      Schluger, N; Karunakara, U; Lienhardt, C; Nyirenda, T E; Chaisson, R; Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University, New York, NY, USA; Campaign for Access to Essential Medicines, Médecins Sans Frontières, Geneva, Switzerland; Clinical Trial Division, International Union Against Tuberculosis and Lung Disease, Paris, France; European and Developing Countries Clinical Trials Partnership, Cape Town, South Africa; Center for TB Research, Johns Hopkins University, Baltimore, MD, USA (2007-11-06)
    • The burden and outcomes of childhood tuberculosis in Cotonou, Benin

      Ade, S; Harries, A D; Trébucq, A; Hinderaker, S G; Ade, G; Agodokpessi, G; Affolabi, D; Koumakpaï, S; Anagonou, S; Gninafon, M (International Union Against TB and Lung Disease, 2013-03)
    • The burden and treatment outcomes of extra-pulmonary tuberculosis in Bhutan

      Jamtsho, T; Harries, A D; Malhotra, S; Wangchuk, D; Dophu, U; Dorji, T; Dendup, T (2013-03)
    • 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.