• Are tuberculosis patients in a tertiary care hospital in Hyderabad, India being managed according to national guidelines?

      Kondapaka, K K; Prasad, S V; Satyanarayana, S; Kandi, S; Zachariah, R; Harries, A D; Nagaraja, S B; Tetali, S; Anchala, R; Kannuri, N K; et al. (Public Library of Science (PLoS), 2012-01-17)
      A tertiary health care facility (Government General and Chest hospital) in Hyderabad, India.
    • Doing no harm? Adverse events in a nation-wide cohort of patients with multidrug-resistant tuberculosis in Nigeria

      Avong, Y K; Isaakidis, P; Hinderaker, S G; Van den Bergh, R; Ali, E; Obembe, B O; Ekong, E; Adebamowo, C; Ndembi, N; Okuma, J; et al. (Public Library of Science, 2015-03-17)
      Adverse events (AEs) of second line anti-tuberculosis drugs (SLDs) are relatively well documented. However, the actual burden has rarely been described in detail in programmatic settings. We investigated the occurrence of these events in the national cohort of multidrug-resistant tuberculosis (MDR-TB) patients in Nigeria.
    • High Prevalence of Tuberculosis and Serious Bloodstream Infections in Ambulatory Individuals Presenting for Antiretroviral Therapy in Malawi

      Bedell, R A; Anderson, S T B; van Lettow, M; Åkesson, A; Corbett, E L; Kumwenda, M; Chan, A K; Heyderman, R S; Zachariah, R; Harries, A D; et al. (Public Library of Science (PLoS), 2011-06-22)
      Background Tuberculosis (TB) and serious bloodstream infections (BSI) may contribute to the high early mortality observed among patients qualifying for antiretroviral therapy (ART) with unexplained weight loss, chronic fever or chronic diarrhea. Methods and Findings A prospective cohort study determined the prevalence of undiagnosed TB or BSI among ambulatory HIV-infected adults with unexplained weight loss and/or chronic fever, or diarrhea in two routine program settings in Malawi. Subjects with positive expectorated sputum smears for AFB were excluded. Investigations Bacterial and mycobacterial blood cultures, cryptococcal antigen test (CrAg), induced sputum (IS) for TB microscopy and solid culture, full blood count and CD4 lymphocyte count. Among 469 subjects, 52 (11%) had microbiological evidence of TB; 50 (11%) had a positive (non-TB) blood culture and/or positive CrAg. Sixty-five additional TB cases were diagnosed on clinical and radiological grounds. Nontyphoidal Salmonellae (NTS) were the most common blood culture pathogens (29 cases; 6% of participants and 52% of bloodstream isolates). Multivariate analysis of baseline clinical and hematological characteristics found significant independent associations between oral candidiasis or lymphadenopathy and TB, marked CD4 lymphopenia and NTS infection, and severe anemia and either infection, but low positive likelihood ratios (<2 for all combinations). Conclusions We observed a high prevalence of TB and serious BSI, particularly NTS, in a program cohort of chronically ill HIV-infected outpatients. Baseline clinical and hematological characteristics were inadequate predictors of infection. HIV clinics need better rapid screening tools for TB and BSI. Clinical trials to evaluate empiric TB or NTS treatment are required in similar populations.
    • How Do Patients Who Fail First-Line TB Treatment but Who Are Not Placed on an MDR-TB Regimen Fare in South India?

      Burugina Nagaraja, S; Satyanarayana, S; Chadha, S S; Kalemane, S; Jaju, J; Achanta, S; Reddy, K; Potharaju, V; Motta Shamrao, S R; Dewan, P; et al. (2011-10)
    • "Life continues": Patient, health care and community care workers perspectives on self-administered treatment for rifampicin-resistant tuberculosis in Khayelitsha, South Africa

      Mohr, E; Snyman, L; Mbakaz, Z; Caldwell, J; DeAzevedo, V; Kock, Y; Trivino Duran, L; Venables, E (Public Library of Science, 2018-09-14)
      Self-administered treatment (SAT), a differentiated model of care for rifampicin-resistant tuberculosis (RR-TB), might address adherence challenges faced by patients and health care systems. This study explored patient, health-care worker (HCW) and community care worker (CCW) perspectives on a SAT pilot programme in South Africa, in which patients were given medication to take at home with the optional support of a CCW.
    • Loss from treatment for drug resistant tuberculosis: risk factors and patient outcomes in a community-based program in Khayelitsha, South Africa

      Moyo, S; Cox, H S; Hughes, J; Daniels, J; Synman, L; De Azevedo, V; Shroufi, A; Cox, V; van Cutsem, G (Public Library of Science, 2015-03-18)
      A community based drug resistant tuberculosis (DR-TB) program has been incrementally implemented in Khayelitsha, a high HIV and TB burden community in South Africa. We investigated loss from treatment (LFT), and post treatment outcomes of DR-TB patients in this setting.
    • Multidrug-resistant tuberculosis treatment outcomes in Karakalpakstan, Uzbekistan: treatment complexity and XDR-TB among treatment failures.

      Cox, H; Kalon, S; Allamuratova, S; Sizaire, V; Tigay, Z; Rüsch-Gerdes, S; Karimovich, H; Kebede, Y; Mills, C; Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Australia. (PLoS, 2007)
      BACKGROUND: A pilot programme to treat multidrug-resistant TB (MDR-TB) was implemented in Karakalpakstan, Uzbekistan in 2003. This region has particularly high levels of MDR-TB, with 13% and 40% among new and previously treated cases, respectively. METHODOLOGY: This study describes the treatment process and outcomes for the first cohort of patients enrolled in the programme, between October 2003 and January 2005. Confirmed MDR-TB cases were treated with an individualised, second-line drug regimen based on drug susceptibility test results, while suspected MDR-TB cases were treated with a standardised regimen pending susceptibility results. PRINCIPAL FINDINGS: Of 108 MDR-TB patients, 87 were started on treatment during the study period. Of these, 33 (38%) were infected with strains resistant to at least one second-line drug at baseline, but none had initial ofloxacin resistance. Treatment was successful for 54 (62%) patients, with 13 (15%) dying during treatment, 12 (14%) defaulting and 8 (8%) failing treatment. Poor clinical condition and baseline second-line resistance contributed to treatment failure or death. Treatment regimens were changed in 71 (82%) patients due to severe adverse events or drug resistance. Adverse events were most commonly attributed to cycloserine, ethionamide and p-aminosalicylic acid. Extensively drug resistant TB (XDR-TB) was found among 4 of the 6 patients who failed treatment and were still alive in November 2006. CONCLUSIONS: While acceptable treatment success was achieved, the complexity of treatment and the development of XDR-TB among treatment failures are important issues to be addressed when considering scaling up MDR-TB treatment.
    • Resistance Patterns among Multidrug-Resistant Tuberculosis Patients in Greater Metropolitan Mumbai: Trends over Time

      Dalal, A; Pawaskar, A; Das, M; Desai, R; Prabhudesai, P; Chhajed, P; Rajan, S; Reddy, D; Babu, S; Jayalakshmi, T K; et al. (Public Library of Science, 2015-01-21)
      While the high burden of multidrug-resistant tuberculosis (MDR-TB) itself is a matter of great concern, the emergence and rise of advanced forms of drug-resistance such as extensively drug-resistant TB (XDR-TB) and extremely drug-resistant TB (XXDR-TB) is more troubling. The aim of this study was to investigate the trends over time of patterns of drug resistance in a sample of MDR-TB patients in greater metropolitan Mumbai, India.
    • Treatment of tuberculosis in a region with high drug resistance: Outcomes, drug resistance amplification and re-infection

      Bonnet, M; Pardini, M; Meacci, F; Orrù, G; Yesilkaya, H; Jarosz, T; Andrew, P W; Barer, M; Checchi, F; Rinder, H; et al. (Public Library of Science, 2011-08-23)
      Introduction: Emerging antituberculosis drug resistance is a serious threat for tuberculosis (TB) control, especially in Eastern European countries. Methods: We combined drug susceptibility results and molecular strain typing data with treatment outcome reports to assess the influence of drug resistance on TB treatment outcomes in a prospective cohort of patients from Abkhazia (Georgia). Patients received individualized treatment regimens based on drug susceptibility testing (DST) results. Definitions for antituberculosis drug resistance and treatment outcomes were in line with current WHO recommendations. First and second line DST, and molecular typing were performed in a supranational laboratory for Mycobacterium tuberculosis (MTB) strains from consecutive sputum smear-positive TB patients at baseline and during treatment. Results: At baseline, MTB strains were fully drug-susceptible in 189/326 (58.0%) of patients. Resistance to at least H or R (PDR-TB) and multidrug-resistance (MDR-TB) were found in 69/326 (21.2%) and 68/326 (20.9%) of strains, respectively. Three MDR-TB strains were also extensively resistant (XDR-TB). During treatment, 3/189 (1.6%) fully susceptible patients at baseline were re-infected with a MDR-TB strain and 2/58 (3.4%) PDR-TB patients became MDR-TB due to resistance amplification. 5/ 47 (10.6%) MDR- patients became XDR-TB during treatment. Treatment success was observed in 161/189 (85.2%), 54/69 (78.3%) and 22/68 (32.3%) of patients with fully drug susceptible, PDR- and MDR-TB, respectively. Development of ofloxacin resistance was significantly associated with a negative treatment outcome. Conclusion: In Abkhazia, a region with high prevalence of drug resistant TB, the use of individualized MDR-TB treatment regimens resulted in poor treatment outcomes and XDR-TB amplification. Nosocomial transmission of MDR-TB emphasizes the importance of infection control in hospitals.
    • Whole Genome Sequencing Reveals Complex Evolution Patterns of Multidrug-Resistant Mycobacterium tuberculosis Beijing Strains in Patients

      Merker, M; Kohl, T A; Roetzer, A; Truebe, L; Richter, E; Rüsch-Gerdes, S; Fattorini, L; Oggioni, M R; Cox, H; Varaine, F; et al. (Public Library of Science, 2013-12)
      Multidrug-resistant (MDR) Mycobacterium tuberculosis complex (MTBC) strains represent a major threat for tuberculosis (TB) control. Treatment of MDR-TB patients is long and less effective, resulting in a significant number of treatment failures. The development of further resistances leads to extensively drug-resistant (XDR) variants. However, data on the individual reasons for treatment failure, e.g. an induced mutational burst, and on the evolution of bacteria in the patient are only sparsely available. To address this question, we investigated the intra-patient evolution of serial MTBC isolates obtained from three MDR-TB patients undergoing longitudinal treatment, finally leading to XDR-TB. Sequential isolates displayed identical IS6110 fingerprint patterns, suggesting the absence of exogenous re-infection. We utilized whole genome sequencing (WGS) to screen for variations in three isolates from Patient A and four isolates from Patient B and C, respectively. Acquired polymorphisms were subsequently validated in up to 15 serial isolates by Sanger sequencing. We determined eight (Patient A) and nine (Patient B) polymorphisms, which occurred in a stepwise manner during the course of the therapy and were linked to resistance or a potential compensatory mechanism. For both patients, our analysis revealed the long-term co-existence of clonal subpopulations that displayed different drug resistance allele combinations. Out of these, the most resistant clone was fixed in the population. In contrast, baseline and follow-up isolates of Patient C were distinguished each by eleven unique polymorphisms, indicating an exogenous re-infection with an XDR strain not detected by IS6110 RFLP typing. Our study demonstrates that intra-patient microevolution of MDR-MTBC strains under longitudinal treatment is more complex than previously anticipated. However, a mutator phenotype was not detected. The presence of different subpopulations might confound phenotypic and molecular drug resistance tests. Furthermore, high resolution WGS analysis is necessary to accurately detect exogenous re-infection as classical genotyping lacks discriminatory power in high incidence settings.
    • Wind-driven roof turbines: a novel way to improve ventilation for TB infection control in health facilities

      Cox, H; Escombe, R; McDermid, C; Mtshemla, Y; Spelman, T; Azevedo, V; London, L; Medecins Sans Frontieres, Cape Town, South Africa; Burnet Institute for Medical Research, Melbourne, Australia; Department of Infectious Diseases and Immunity, Imperial College London, London, United Kingdom; City of Cape Town Health Department, Cape Town, South Africa; University of Cape Town, Cape Town, South Africa (Public Library of Science (PLoS), 2012-01-09)
      Tuberculosis transmission in healthcare facilities contributes significantly to the TB epidemic, particularly in high HIV settings. Although improving ventilation may reduce transmission, there is a lack of evidence to support low-cost practical interventions. We assessed the efficacy of wind-driven roof turbines to achieve recommended ventilation rates, compared to current recommended practices for natural ventilation (opening windows), in primary care clinic rooms in Khayelitsha, South Africa.