• 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.
    • Performance of LED-Based Fluorescence Microscopy to Diagnose Tuberculosis in a Peripheral Health Centre in Nairobi.

      Bonnet, M; Gagnidze, L; Githui, W; Guérin, P J; Bonte, L; Varaine, F; Ramsay, A; Epicentre, France; Centre for Respiratory Diseases Research, Kenya Medical Research Institute, Kenya; Médecins Sans Frontières, France; UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, World Health Organization, Switzerland (2011-02-18)
      Sputum microscopy is the only tuberculosis (TB) diagnostic available at peripheral levels of care in resource limited countries. Its sensitivity is low, particularly in high HIV prevalence settings. Fluorescence microscopy (FM) can improve performance of microscopy and with the new light emitting diode (LED) technologies could be appropriate for peripheral settings. The study aimed to compare the performance of LED-FM versus Ziehl-Neelsen (ZN) microscopy and to assess feasibility of LED-FM at a low level of care in a high HIV prevalence country.
    • Performance of LED-Based Fluorescence Microscopy to Diagnose Tuberculosis in a Peripheral Health Centre in Nairobi.

      Bonnet, M; Gagnidze, L; Githui, W; Guérin, P J; Bonte, L; Varaine, F; Ramsay, A; Epicentre, Paris, France. (PloS One, 2011-02)
      Sputum microscopy is the only tuberculosis (TB) diagnostic available at peripheral levels of care in resource limited countries. Its sensitivity is low, particularly in high HIV prevalence settings. Fluorescence microscopy (FM) can improve performance of microscopy and with the new light emitting diode (LED) technologies could be appropriate for peripheral settings. The study aimed to compare the performance of LED-FM versus Ziehl-Neelsen (ZN) microscopy and to assess feasibility of LED-FM at a low level of care in a high HIV prevalence country.
    • Performance of the 2007 WHO Algorithm to diagnose Smear-negative Pulmonary Tuberculosis in a HIV prevalent setting

      Huerga, H; Varaine, F; Okwaro, E; Bastard, M; Ardizzoni, E; Sitienei, J; Chakaya, J; Bonnet, M; Clinical Research Department, Epicentre, Paris, France. helena.huerga@epicentre.msf.org (2012-12-19)
      The 2007 WHO algorithm for diagnosis of smear-negative pulmonary tuberculosis (PTB) including Mycobacterium tuberculosis (MTB) culture was evaluated in a HIV prevalent area of Kenya.
    • Pharmacokinetics of efavirenz in patients on antituberculosis treatment in high HIV and tuberculosis burden countries: a systematic review

      Atwine, D; Bonnet, M; Taburet, AM (Wiley-Blackwell, 2018-04-06)
      Efavirenz (EFV) and Rifampicin-Isoniazid (RH) are cornerstone drugs in HIV-tuberculosis (TB) co-infection treatment but with complex drug interactions, efficacy and safety challenges. We reviewed recent data on EFV and RH interaction in TB/HIV high-burden countries.
    • Poor Outcomes in a Cohort of HIV-Infected Adolescents Undergoing Treatment for Multidrug-Resistant Tuberculosis in Mumbai, India

      Isaakidis, P; Paryani, R; Khan, S; Mansoor, H; Manglani, M; Valiyakath, A; Saranchuk, P; Furin, J; Médecins Sans Frontières, Mumbai, India. msfocb-asia-epidemio@brussels.msf.org (PLoS, 2013-07-19)
      Little is known about the treatment of multidrug-resistant tuberculosis (MDR-TB) in HIV-co-infected adolescents. This study aimed to present the intermediate outcomes of HIV-infected adolescents aged 10-19 years receiving second-line anti-TB treatment in a Médecins Sans Frontières (MSF) project in Mumbai, India.
    • Population Differences in Death Rates in HIV-Positive Patients with Tuberculosis.

      Ciglenecki, I; Glynn, J R; Mwinga, A; Ngwira, B; Zumla, A; Fine, P E M; Nunn, A; Médecins Sans Frontières, Geneva, Switzerland. iza_ciglenecki@yahoo.com (International Union Against TB and Lung Disease, 2007-10)
      SETTING: Randomised controlled clinical trial of Mycobacterium vaccae vaccination as an adjunct to anti-tuberculosis treatment in human immunodeficiency virus (HIV) positive patients with smear-positive tuberculosis (TB) in Lusaka, Zambia, and Karonga, Malawi. OBJECTIVE: To explain the difference in mortality between the two trial sites and to identify risk factors for death among HIV-positive patients with TB. DESIGN: Information on demographic, clinical, laboratory and radiographic characteristics was collected. Patients in Lusaka (667) and in Karonga (84) were followed up for an average of 1.56 years. Cox proportional hazard analyses were used to assess differences in survival between the two sites and to determine risk factors associated with mortality during and after anti-tuberculosis treatment. RESULTS: The case fatality rate was 14.7% in Lusaka and 21.4% in Karonga. The hazard ratio for death comparing Karonga to Lusaka was 1.47 (95% confidence interval [CI] 0.9-2.4) during treatment and 1.76 (95%CI 1.0-3.0) after treatment. This difference could be almost entirely explained by age and more advanced HIV disease among patients in Karonga. CONCLUSION: It is important to understand the reasons for population differences in mortality among patients with TB and HIV and to maximise efforts to reduce mortality.
    • Pre-treatment loss to follow-up among smear-positive pulmonary tuberculosis cases: a 10-year audit of national data from Fiji

      Ram, S; Kishore, K; Batio, I; Bissell, K; Zachariah, R; Satyanarayana, S; Harries, A D (TB Union, 2013-02-14)
    • Precision medicine for drug-resistant tuberculosis in high-burden countries: is individualised treatment desirable and feasible?

      Cox, H; Hughes, J; Black, J; Nicol, MP (Elsevier, 2018-03-13)
      Treatment for drug-resistant tuberculosis is largely delivered through standardised, empirical combination regimens in low-resource, high-burden settings. However, individualised treatment, guided by detailed drug susceptibility testing, probably results in improved individual outcomes and is the standard of care in well-resourced settings. Driven by the urgent need to scale up treatment provision, new tuberculosis drugs, incorporated into standardised regimens, are being tested. Although standardised regimens are expected to improve access to treatment in high-burden settings, they are also likely to contribute to the emergence of resistance, even with good clinical management. We argue that a balance is required between the need to improve treatment access and the imperative to minimise resistance amplification and provide the highest standard of care, through a precision medicine approach. In tuberculosis, as in other diseases, we should aim to reduce the entrenched inequalities that manifest as different standards of care in different settings.
    • Predictive Modeling Targets Thymidylate Synthase ThyX in Mycobacterium Tuberculosis

      Djaout, K; Singh, V; Boum, Y; Katawera, V; Becker, H F; Bush, N G; Hearnshaw, S J; Pritchard, J E; Bourbon, P; Madrid, P B; et al. (Nature Publishing Group, 2016-06-10)
      There is an urgent need to identify new treatments for tuberculosis (TB), a major infectious disease caused by Mycobacterium tuberculosis (Mtb), which results in 1.5 million deaths each year. We have targeted two essential enzymes in this organism that are promising for antibacterial therapy and reported to be inhibited by naphthoquinones. ThyX is an essential thymidylate synthase that is mechanistically and structurally unrelated to the human enzyme. DNA gyrase is a DNA topoisomerase present in bacteria and plants but not animals. The current study set out to understand the structure-activity relationships of these targets in Mtb using a combination of cheminformatics and in vitro screening. Here, we report the identification of new Mtb ThyX inhibitors, 2-chloro-3-(4-methanesulfonylpiperazin-1-yl)-1,4-dihydronaphthalene-1,4-dione) and idebenone, which show modest whole-cell activity and appear to act, at least in part, by targeting ThyX in Mtb.
    • Predictors of Delayed Culture Conversion Among Ugandan Patients

      Atwine, D; Orikiriza, P; Taremwa, I; Ayebare, A; Logoose, S; Mwanga-Amumpaire, J; Jindani, A; Bonnet, M (BioMed Central, 2017-04-24)
      Estimates of month-2 culture conversion, a proxy indicator of tuberculosis (TB) treatment efficacy in phase-2 trials can vary by culture-type and geographically with lower rates reported among African sites. The sub-study aimed at comparing TB detection rates of different culture media, within and across rifampicin-based regimens (R10, 15 and 20 mg/Kg) over a 6-month treatment follow-up period, and to establish predictors of month-2 culture non-conversion among HIV-negative TB patients enrolled at RIFATOX trial site in Uganda.
    • Prevalence, features and risk factors for malaria co-infections amongst visceral leishmaniasis patients from Amudat Hospital, Uganda.

      van den Bogaart, E; Berkhout, M M Z; Adams, E R; Mens, P F; Sentongo, E; Mbulamberi, D B; Straetemans, M; Schallig, H D F H; Chappuis, F; Department of Biomedical Research, Royal Tropical Institute (KIT), Amsterdam, The Netherlands; Department of Medical Microbiology, Makerere University College of Health Sciences, Kampala, Uganda; Ministry of Health, Kampala, Uganda; Médecins Sans Frontières, Geneva, Switzerland; Geneva University Hospitals and University of Geneva, Geneva, Switzerland (Public Library of Medicine (PLoS), 2012-04-10)
      Due to geographic overlap of malaria and visceral leishmaniasis (VL), co-infections may exist but have been poorly investigated. To describe prevalence, features and risk factors for VL-malaria co-infections, a case-control analysis was conducted on data collected at Amudat Hospital, Uganda (2000-2006) by Médecins sans Frontières. Cases were identified as patients with laboratory-confirmed VL and malaria at hospital admission or during hospitalization; controls were VL patients with negative malaria smears. A logistic regression analysis was performed to study the association between patients' characteristics and the occurrence of the co-infection.
    • Prevention of Hearing Loss in Patients with Multidrug-Resistant Tuberculosis

      Cox, H; Reuter, A; Furin, J; Seddon, J (Elsevier, 2017-09-02)