• 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.
    • 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.
    • Effect of Antiretroviral Therapy on the Diagnostic Accuracy of Symptom Screening for Intensified Tuberculosis Case Finding in a South African HIV clinic

      Rangaka, M X; Wilkinson, R J; Glynn, J R; Boulle, A; van Cutsem, G; Goliath, R; Mathee, S; Maartens, G; Centre for Infectious Disease Research and Epidemiology, School of Public Health and Family Medicine, University of Cape Town, South Africa. mxrangaka@yahoo.co.uk (Oxford University Press, 2012-12)
      Current symptom screening algorithms for intensified tuberculosis case finding or prior to isoniazid preventive therapy (IPT) in patients infected with human immunodeficiency virus (HIV) were derived from antiretroviral-naive cohorts. There is a need to validate screening algorithms in patients on antiretroviral therapy (ART).
    • The emerging crisis of drug-resistant tuberculosis in South Africa: lessons from New York City.

      Murphy, R A; Division of Infectious Diseases, Massachusetts General Hospital and Brigham and Women's Hospital, Boston, Massachusetts, USA. richard.murphy@newyork.msf.org (2008-06-01)
      Multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis have emerged as important infections in South Africa among patients infected with human immunodeficiency virus (HIV). In the face of this new epidemic, South Africa must rededicate itself to the task of tuberculosis control and treatment with a rapid, multifaceted approach. Priorities include expansion of second-line treatment capacity, investment in clinical laboratories, a system to ensure supervised treatment for all patients, and enhancement of infection control procedures. In New York City, where drug-resistant tuberculosis emerged 2 decades ago--also in the context of a large HIV-infected population and an underfunded public health infrastructure--similar steps were successful in leading to the rapid decrease in rates of drug resistance among tuberculosis isolates. With refinements based on local resource constraints, urgent measures could potentially arrest the alarming increase in multidrug-resistant and extensively drug-resistant tuberculosis cases in South Africa. Unlike many countries in sub-Saharan Africa, South Africa has the capacity to mount a rapid and large-scale response before drug-resistant tuberculosis envelops a much larger and far poorer region.
    • Infection Control for Drug-Resistant Tuberculosis: Early Diagnosis and Treatment Is the Key

      van Cutsem, G; Isaakidis, P; Farley, J; Nardell, E; Volchenkov, G; Cox, H (Oxford University Press -- We regret that this article is behind a paywall., 2016-05-15)
      Multidrug-resistant (MDR) tuberculosis, "Ebola with wings," is a significant threat to tuberculosis control efforts. Previous prevailing views that resistance was mainly acquired through poor treatment led to decades of focus on drug-sensitive rather than drug-resistant (DR) tuberculosis, driven by the World Health Organization's directly observed therapy, short course strategy. The paradigm has shifted toward recognition that most DR tuberculosis is transmitted and that there is a need for increased efforts to control DR tuberculosis. Yet most people with DR tuberculosis are untested and untreated, driving transmission in the community and in health systems in high-burden settings. The risk of nosocomial transmission is high for patients and staff alike. Lowering transmission risk for MDR tuberculosis requires a combination approach centered on rapid identification of active tuberculosis disease and tuberculosis drug resistance, followed by rapid initiation of appropriate treatment and adherence support, complemented by universal tuberculosis infection control measures in healthcare facilities. It also requires a second paradigm shift, from the classic infection control hierarchy to a novel, decentralized approach across the continuum from early diagnosis and treatment to community awareness and support. A massive scale-up of rapid diagnosis and treatment is necessary to control the MDR tuberculosis epidemic. This will not be possible without intense efforts toward the implementation of decentralized, ambulatory models of care. Increasing political will and resources need to be accompanied by a paradigm shift. Instead of focusing on diagnosed cases, recognition that transmission is driven largely by undiagnosed, untreated cases, both in the community and in healthcare settings, is necessary. This article discusses this comprehensive approach, strategies available, and associated challenges.
    • One step forward: Successful end-of-treatment outcomes of drug-resistant TB patients who received concomitant bedaquiline and delamanid in Mumbai, India

      Das, M; Dalal, A; Laxmeshwar, C; Ravi, S; Mamnoon, F; Meneguim, AC; Paryani, R; Mathur, T; Singh, P; Mansoor, H; et al. (Oxford University Press, 2020-10-20)
      Background Médecins Sans Frontières clinic in Mumbai, India has been providing concomitant Bedaquiline (BDQ) and Delamanid (DLM) in treatment regimen for patients with drug-resistant tuberculosis (DR-TB) and limited therapeutic options, referred from other healthcare institutions, since 2016. The study documents the end-of-treatment outcomes, culture-conversion rates, and serious adverse events (SAEs) during treatment. Methods This was a retrospective cohort study based on routinely collected programme data. In clinic, treatment regimens are designed based on culture-drug sensitivity test patterns, previous drug-exposures and are provided for 20-22 months. The BDQ and DLM are extended beyond 24 weeks as off-label use. Patients who initiated DR-TB treatment including BDQ and DLM (concomitantly for at least 4 weeks) during February2016-February2018 were included. Result Of the 70 patients included, the median (IQR) age was 25(22-32) years and 56% were females. All except one were fluoroquinolone resistant. The median(IQR) duration of exposure to BDQ and DLM was 77(43-96) weeks. Thirty-nine episodes of serious-adverse-events(SAEs) were reported among 30(43%) patients, including five instances of QTc prolongation-assessed as possibly related to BDQ and/or DLM. Majority(69%) had culture conversion before 24 weeks of treatment. In 61(87%), use of BDQ and DLM was extended beyond 24 weeks. Successful end-of-treatment outcomes were reported in 49(70%) patients. Conclusion The successful treatment outcomes of this cohort show that regimens including concomitant bedaquiline and delamanid for longer than 24 weeks are effective and can be safely administered on ambulatory basis. National TB programmes globally should scale up access to life saving DR-TB regimens with new drugs.
    • Risk of acquired drug resistance during short-course directly observed treatment of tuberculosis in an area with high levels of drug resistance.

      Cox, H; Niemann, S; Ismailov, G; Doshetov, D; Orozco, J D; Blok, L; Rüsch-Gerdes, S; Kebede, Y; Australian International Health Institute, University of Melbourne, Australia. (Infectious Disease Society of America, 2007-06-01)
      BACKGROUND: Data on the performance of standardized short-course directly observed treatment (DOTS) of tuberculosis (TB) in areas with high levels of drug resistance and on the potential impact of DOTS on amplification of resistance are limited. Therefore, we analyzed treatment results from a cross-sectional sample of patients with TB enrolled in a DOTS program in an area with high levels of drug resistance in Uzbekistan and Turkmenistan in Central Asia. METHODS: Sputum samples for testing for susceptibility to 5 first-line drugs and for molecular typing were obtained from patients starting treatment in 8 districts. Patients with sputum smear results positive for TB at the end of the intensive phase of treatment and/or at 2 months into the continuation phase were tested again. RESULTS. Among 382 patients with diagnoses of TB, 62 did not respond well to treatment and were found to be infected with an identical Mycobacterium tuberculosis strain when tested again; 19 of these patients had strains that developed new or additional drug resistance. Amplification occurred in only 1.2% of patients with initially susceptible or monoresistant TB strains, but it occurred in 17% of those with polyresistant strains (but not multidrug-resistant strains, defined as strains with resistance to at least isoniazid and rifampicin) and in 7% of those with multidrug-resistant strains at diagnosis. Overall, 3.5% of the patients not initially infected with multidrug-resistant TB strains developed such strains during treatment. Amplification of resistance, however, was found only in polyresistant Beijing genotype strains. CONCLUSIONS: High levels of amplification of drug resistance demonstrated under well-established DOTS program conditions reinforce the need for implementation of DOTS-Plus for multidrug-resistant TB in areas with high levels of drug resistance. The strong association of Beijing genotype and amplification in situations of preexisting resistance is striking and may underlie the strong association between this genotype and drug resistance.
    • Safety and effectiveness of an all-oral, bedaquiline-based, shorter treatment regimen for rifampicin-resistant tuberculosis in high HIV burden rural South Africa: a retrospective cohort analysis

      Tack, I; Dumicho, A; Ohler, L; Shigayeva, A; Bulti, AB; White, K; Mbatha, M; Furin, J; Isaakidis, P (Oxford University Press, 2020-12-29)
      Background At the end of 2018, South Africa updated its all-oral regimen, to include bedaquiline (BDQ) and two months of linezolid (LZD) for all patients initiating the shorter 9 to 12 months regimen for rifampicin-resistant tuberculosis (RR-TB). We assessed a group of patients in rural KwaZulu-Natal for safety and effectiveness of this treatment regimen under programmatic conditions. Methods We conducted a retrospective cohort analysis on RR-TB patients treated with a standardized all-oral short regimen between July 1, 2018 and April 30, 2019 in three facilities in King Cetshwayo District. An electronic register (EDR Web) and facility-based clinical charts were used to collect variables which were entered into an Epi-Info database. Results Our cohort included 117 patients; 68.4%(95%CI:59.3-76.3) were HIV positive. The median time to culture conversion was 56 days(95%CI:50-57). Treatment success was achieved in 75.2%(95%CI:66.5-82.3) of patients. Mortality within the cohort was 12.8%(95%CI:7.8-20.3). Anaemia was the most frequent severe adverse event. The median time to develop severe anaemia was 7.1 weeks(IQR 4.0-12.9) after treatment initiation. LZD was interrupted in 25.2%(95%CI:17.8-34.5) of participants. Conclusions An all-oral shorter regimen, including BDQ and LZD as core drugs for the treatment of RR-TB, shows good outcomes, in a high HIV burden rural setting. Adverse events (AEs) are common, especially for LZD, but could be managed in the program setting. Support is needed when introducing new regimens to upskill staff in the monitoring, management and reporting of AEs.
    • 'SILVAMP TB LAM' rapid urine tuberculosis test predicts mortality in hospitalized HIV patients in South Africa.

      Sossen, B; Broger, T; Kerkhoff, AD; Schutz, C; Trollip, A; Moreau, E; Schumacher, SG; Burton, R; Ward, A; Wilkinson, RJ; et al. (Oxford University Press, 2020-01-09)
      Reducing diagnostic delay is key towards decreasing tuberculosis-associated deaths in people living with HIV. In tuberculosis patients with retrospective urine testing, the point-of-care Fujifilm SILVAMP TB LAM (FujiLAM) could have rapidly diagnosed tuberculosis in up to 89% who died. In FujiLAM negative patients, the probability of 12-week survival was 86-97%.
    • Treating drug-resistant tuberculosis infection: no more excuses

      Reuter, A; Furin, J (Oxford University Press, 2020-04-08)
    • Treatment outcomes of patients switching from an injectable drug to bedaquiline during short standardized MDR-TB treatment in Mozambique

      Bastard, M; Molfino, L; Mutaquiha, C; Galindo, MA; Zindoga, P; Vaz, D; Mahinca, I; du Cros, P; Rusch, B; Telnov, A (Oxford University Press, 2019-03-11)
      Bedaquiline was recommended by WHO as the preferred option in treatment of MDR-TB patients with long regimen. However, no recommendation was given for the short MDR-TB regimen. Data from our small cohort of patients who switched injectable dug to bedaquiline suggest that bedaquiline based short regimen is effective and safe.