• GeneXpert and Community Health Workers Supported Patient Tracing for Tuberculosis Diagnosis in Conflict-Affected Border Areas in India

      Isaakidis, P; Ferlazzo, G; Das, M; Pasupuleti, D; Sloan, S; Hossain, F; Kalon, S; Mansoor, H; Rao, S (MDPI AG, 2019-12-21)
      Abstract: Médecins Sans Frontières (MSF) has been providing diagnosis and treatment for patients with tuberculosis (TB) via mobile clinics in conflict-affected border areas of Chhattisgarh, India since 2009. The study objectives were to determine the proportion of patients diagnosed with TB and those who were lost-to-follow-up (LTFU) prior to treatment initiation among patients with presumptive TB between April 2015 and August 2018. The study also compared bacteriological confirmation and pretreatment LTFU during two time periods: a) April 2015–August 2016 and b) April 2017–August 2018 (before and after the introduction of GeneXpert as a first diagnostic test). Community health workers (CHW) supported patient tracing. This study was a retrospective analysis of routine program data. Among 1042 patients with presumptive TB, 376 (36%) were diagnosed with TB. Of presumptive TB patients, the pretreatment LTFU was 7%. Upon comparing the two time-periods, bacteriological confirmation increased from 20% to 33%, while pretreatment LTFU decreased from 11% to 4%. TB diagnosis with GeneXpert as the first diagnostic test and CHW-supported patient tracing in a mobile-clinic model of care shows feasibility for replication in similar conflict-affected, hard to reach areas.
    • GeneXpert and Community Health Workers Supported Patient Tracing for Tuberculosis Diagnosis in Conflict-Affected Border Areas in India.

      Das, M; Pasupuleti, D; Rao, S; Sloan, S; Mansoor, H; Kalon, S; Hossain, F; Ferlazzo, G; Isaakidis, P (MDPI AG, 2019-12-21)
      Médecins Sans Frontières (MSF) has been providing diagnosis and treatment for patients with tuberculosis (TB) via mobile clinics in conflict-affected border areas of Chhattisgarh, India since 2009. The study objectives were to determine the proportion of patients diagnosed with TB and those who were lost-to-follow-up (LTFU) prior to treatment initiation among patients with presumptive TB between April 2015 and August 2018. The study also compared bacteriological confirmation and pretreatment LTFU during two time periods: a) April 2015–August 2016 and b) April 2017–August 2018 (before and after the introduction of GeneXpert as a first diagnostic test). Community health workers (CHW) supported patient tracing. This study was a retrospective analysis of routine program data. Among 1042 patients with presumptive TB, 376 (36%) were diagnosed with TB. Of presumptive TB patients, the pretreatment LTFU was 7%. Upon comparing the two time-periods, bacteriological confirmation increased from 20% to 33%, while pretreatment LTFU decreased from 11% to 4%. TB diagnosis with GeneXpert as the first diagnostic test and CHW-supported patient tracing in a mobile-clinic model of care shows feasibility for replication in similar conflict-affected, hard to reach areas.
    • Global programmatic use of bedaquiline and delamanid for the treatment of multidrug-resistant tuberculosis

      Cox, V; Brigden, G; Crespo, RH; Lessem, E; Lynch, S; Rich, ML; Waning, B; Furin, J (International Union Against Tuberculosis and Lung Disease, 2018-04-01)
      The World Health Organization recommended two new drugs, bedaquiline (BDQ) and delamanid (DLM), for the treatment of multidrug-resistant tuberculosis (MDR-TB) in 2013 and 2014, respectively. An estimated one third of patients with MDR-TB would benefit from the inclusion of these drugs in their treatment regimens.
    • Hepple - Microscopy compared to culture for the diagnosis of Tuberculosis in Induced Sputum samples; a systematic review

      Hepple, P; Ford, N; McNerney, R; Manson Unit, Médecins Sans Frontières, London, UK. pamela.hepple@london.msf.org (2012-03-07)
      Resource-limited settings rely on sputum examination using microscopy to diagnose tuberculosis (TB); however, the sensitivity of the test is poor and case detection rates are low. Sputum induction is proposed as a way to improve sample collection and enhance test sensitivity.
    • High Activation of γδ T Cells and the γδ2 T-Cell Subset Is Associated With the Onset of Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome, ANRS 12153 CAPRI NK.

      Polidy, P; Nouhin, J; Ratana, M; Madec, Y; Borand, L; Marcy, O; Laureillard, D; Fernandez, M; Barre-Sionussi, F; Weiss, L; et al. (Frontiers Media, 2019-08-09)
      Background: Human Immunodeficiency Virus 1 (HIV-1) and Mycobacterium Tuberculosis (Mtb) co-infected patients are commonly at risk of immune reconstitution inflammatory syndrome (IRIS) when initiating antiretroviral treatment (ART). Evidence indicates that innate immunity plays a role in TB-IRIS. Here, we evaluate the phenotype of Gamma-delta (γδ) T cells and invariant Natural Killer (iNK) T cells in tuberculosis-associated IRIS. Methods: Forty-eight HIV+/TB+ patients (21 IRIS) and three control groups: HIV-/TB- (HD, n = 11), HIV+/TB- (n = 26), and HIV-/TB+ (n = 22) were studied. Samples were taken at ART initiation (week 2 of anti-tuberculosis treatment) and at the diagnosis of IRIS for HIV+/TB+; before ART for HIV+/TB-, and at week 2 of anti-tuberculosis treatment for HIV-/TB+ patients. γδ T cells and Invariant natural killer T (iNKT) cells were analyzed by flow cytometry. Results: Before ART, IRIS, and non-IRIS patients showed a similar proportion of γδpos T and iNKT cells. HLA-DR on γδpos T cells and δ2posγδpos T cells was significantly higher in TB-IRIS vs. non-IRIS patients and controls (p < 0.0001). NKG2D expression on γδpos T cells and the δ2posγδpos T cell subset was lower in HIV+/TB+ patients than controls. CD158a expression on γδpos T cells was higher in TB-IRIS than non-IRIS (p = 0.02), HIV+/TB-, and HIV-/TB- patients. Conclusion: The higher activation of γδposT cells and the γδ2posγδpos T cell subset suggests that γδ T cells may play a role in the pathogenesis of TB-IRIS.
    • High adherence to anti-tuberculosis treatment among patients attending a hospital and slum health centre in Nairobi, Kenya

      Raguenaud, M E; Zachariah, R; Massaquoi, M; Ombeka, V; Ritter, H; Chakaya, J; Medecins Sans Fronteres (Taylor & Francis, 2008-10-22)
      We conducted a study among patients with tuberculosis (TB) attending two health facilities - a hospital and a slum health centre - in Nairobi, in order to: (a) assess adherence to anti-TB treatment; and (b) identify reasons for non-adherence. Urine Isoniazid (INH), used as a proxy for overall adherence, was detected in 142 (97%) (95% CI 92-99) of the 147 patients involved in the study. Five patients had no INH detected in urine and had run out of pills within the previous three days. The reasons included: not having enough pills to last until the next appointment date (1); and losing some pills (1). Anti-TB treatment adherence is high, and is reassuring information as Kenya plans to change to a superior first-line regimen based on rifampicin throughout the course of anti-TB treatment. Providing patients with a three-day "excess stock" of pills would provide a "safety net" for continued treatment.
    • High initial default in patients with smear-positive pulmonary tuberculosis at a regional hospital in Accra, Ghana

      Afutu, F K; Zachariah, R; Hinderaker, S G; Ntoah-Boadi, H; Obeng, E A; Bonsu, F A; Harries, A D (2012-08)
    • High Prevalence of Infection and Low Incidence of Disease in Child Contacts of Patients with Drug-resistant Tuberculosis: a Prospective Cohort Study

      Huerga, H; Sanchez-Padilla, E; Melikyan, N; Atshemyan, H; Hayrapetyan, A; Ulumyan, A; Bastard, M; Khachatryan, N; Hewison, C; Varaine, F; et al. (BMJ, 2018-12-06)
      We aimed to measure the prevalence and incidence of latent tuberculosis infection (LTBI) and tuberculosis (TB) disease in children in close contact with patients with drug-resistant TB (DR-TB) in a country with high DR-TB prevalence.
    • High prevalence of infection and low incidence of disease in child contacts of patients with drug-resistant tuberculosis: a prospective cohort study

      Huerga, H; Sanchez-Padilla, E; Melikyan, N; Atshemyan, H; Hayrapetyan, A; Ulumyan, A; Bastard, M; Khachatryan, N; Hewison, C; Varaine, F; et al. (The BMJ, 2019-07)
      Objective We aimed to measure the prevalence and incidence of latent tuberculosis infection (LTBI) and tuberculosis (TB) disease in children in close contact with patients with drug-resistant TB (DR-TB) in a country with high DR-TB prevalence. Design and setting This is a prospective cohort study of paediatric contacts of adult patients with pulmonary DR-TB in Armenia. Children were screened using tuberculin skin test, interferon-gamma release assay and chest X-ray at the initial consultation, and were reassessed every 3–6 months for a period of 24 months. Children did not receive preventive treatment. Main outcome measures Prevalence and incidence of LTBI and TB disease; factors associated with prevalent LTBI. Results At initial evaluation, 3 of the 150 children included were diagnosed with TB disease (2.0%). The prevalence of LTBI was 58.7%. The incidence of LTBI was 19.9 per 100 children per year, and was especially high during the first 6 months of follow-up (33.3 per 100 children per year). No additional cases with incident disease were diagnosed during follow-up. After adjustment, prevalent LTBI was significantly associated with the child’s age, sleeping in the same house, higher household density, the index case’s age, positive smear result and presence of lung cavities. Conclusions Children in close contact with patients with DR-TB or in contact with very contagious patients had an increased risk of prevalent LTBI. Although none of the children developed TB disease during a 2-year follow-up period, screening for symptoms of TB disease, based on the prevalence of disease at recruitment, together with follow-up and repeated testing of non-infected contacts, is highly recommended in paediatric contacts of patients with DR-TB.
    • High prevalence of multidrug-resistant tuberculosis, Swaziland, 2009-2010

      Sanchez-Padilla, E; Dlamini, T; Ascorra, A; Rüsch-Gerdes, S; Tefera, Z D; Calain, P; de la Tour, R; Jochims, F; Richter, E; Bonnet, M; et al. (Center for Disease Control, 2012-01)
      In Africa, although emergence of multidrug-resistant (MDR) tuberculosis (TB) represents a serious threat in countries severely affected by the HIV epidemic, most countries lack drug-resistant TB data. This finding was particularly true in the Kingdom of Swaziland, which has the world's highest HIV and TB prevalences. Therefore, we conducted a national survey in 2009-2010 to measure prevalence of drug-resistant TB. Of 988 patients screened, 420 new case-patients and 420 previously treated case-patients met the study criteria. Among culture-positive patients, 15.3% new case-patients and 49.5% previously treated case-patients harbored drug-resistant strains. MDR TB prevalence was 7.7% and 33.8% among new case-patients and previously treated case-patients, respectively. HIV infection and past TB treatment were independently associated with MDR TB. The findings assert the need for wide-scale intervention in resource-limited contexts such as Swaziland, where diagnostic and treatment facilities and health personnel are lacking.
    • 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.
    • High prevalence of undiagnosed diabetes among tuberculosis patients in peripheral health facilities in Kerala

      Nair, S; Kumari, A K; Subramonianpillai, J; Shabna, D S; Kumar, S M; Balakrishnan, S; Naik, B; Kumar, A M V; Isaakidis, P; Satyanarayana, S (International Union Against TB and Lung Disease, 2013-11)
    • High Rate of Hypothyroidism in Multidrug-Resistant Tuberculosis Patients Co-Infected with HIV in Mumbai, India.

      Andries, A; Isaakidis, P; Das, M; Khan, S; Paryani, R; Desai, C; Dalal, A; Mansoor, H; Verma, R; Fernandes, D; et al. (PLoS, 2013-10-23)
      Adverse events (AEs) among HIV-infected patients with multidrug-resistant tuberculosis (MDR-TB) receiving anti-TB and antiretroviral treatments (ART) are under-researched and underreported. Hypothyroidism is a common AE associated with ethionamide, p-aminosalicylic acid (PAS), and stavudine. The aim of this study was to determine the frequency of and risk factors associated with hypothyroidism in HIV/MDR-TB co-infected patients.
    • High treatment success rate for multidrug-resistant and extensively drug-resistant tuberculosis using a bedaquiline-containing treatment regimen

      Ndjeka, N; Schnippel, K; Master, I; Meintjes, G; Maartens, G; Romero, R; Padanilam, X; Enwerem, M; Chotoo, S; Singh, N; et al. (European Respiratory Society, 2018-10-25)
      Background: South African patients with rifampicin-resistant tuberculosis and resistance to fluoroquinolones and/or injectables (pre/XDR-TB) were granted access to bedaquiline through a Clinical Access Programme with strict inclusion and exclusion criteria.Methods: Pre/XDR-TB and XDR-TB patients were treated with 24 weeks bedaquiline within an optimised, individualised background regimen that could include levofloxacin, linezolid and clofazimine as needed.Results: 200 patients were enrolled: 87 (43.9%) with XDR-TB, 99 (49.3%) were female, median age 34 years (IQR 27, 42). 134 (67.0%) were living with HIV; median CD4+ 281 (IQR 130; 467) and all on antiretroviral therapy.16/200 patients (8.0%) did not complete 6 months of bedaquiline of which 8 were lost to follow up, 6 died, 1 stopped for side effects and 1 patient was diagnosed with drug-sensitive TB.146/200 (73.0%) patients had favourable outcomes: 139/200 were cured (69.5%) and 7 completed treatment (3.5%). 25 died (12.5%), were lost from treatment (10.0%), 9 had treatment failure (4.5%).22 adverse events were attributed to bedaquiline: including QTcF >500 ms (n=5), QTcF increase >50 ms from baseline (n=11), paroxysmal atrial flutter (n=1).Conclusion: Bedaquiline added to an optimised background regimen was associated with a high rate of successful treatment outcomes for this MDR-TB and XDR-TB cohort.
    • HIV testing in people with presumptive tuberculosis: time for implementation

      Kumar, A M V; Gupta, D; Gupta, R S; Satyanarayana, S; Wilson, N; Zachariah, R; Lawn, S D; Harries, A D (2012-09)
    • The HIV-associated tuberculosis epidemic--when will we act?

      Harries, A D; Zachariah, R; Corbett, E L; Lawn, S D; Santos-Filho, E T; Chimzizi, R; Harrington, M; Maher, D; Williams, B G; De Cock, K M; et al. (2010-05-29)
      Despite policies, strategies, and guidelines, the epidemic of HIV-associated tuberculosis continues to rage, particularly in southern Africa. We focus our attention on the regions with the greatest burden of disease, especially sub-Saharan Africa, and concentrate on prevention of tuberculosis in people with HIV infection, a challenge that has been greatly neglected. We argue for a much more aggressive approach to early diagnosis and treatment of HIV infection in affected communities, and propose urgent assessment of frequent testing for HIV and early start of antiretroviral treatment (ART). This approach should result in short-term and long-term declines in tuberculosis incidence through individual immune reconstitution and reduced HIV transmission. Implementation of the 3Is policy (intensified tuberculosis case finding, infection control, and isoniazid preventive therapy) for prevention of HIV-associated tuberculosis, combined with earlier start of ART, will reduce the burden of tuberculosis in people with HIV infection and provide a safe clinical environment for delivery of ART. Some progress is being made in provision of HIV care to HIV-infected patients with tuberculosis, but too few receive co-trimoxazole prophylaxis and ART. We make practical recommendations about how to improve this situation. Early HIV diagnosis and treatment, the 3Is, and a comprehensive package of HIV care, in association with directly observed therapy, short-course (DOTS) for tuberculosis, form the basis of prevention and control of HIV-associated tuberculosis. This call to action recommends that both HIV and tuberculosis programmes exhort implementation of strategies that are known to be effective, and test innovative strategies that could work. The continuing HIV-associated tuberculosis epidemic needs bold but responsible action, without which the future will simply mirror the past.
    • "Home is where the patient is": a qualitative analysis of a patient-centred model of care for multi-drug resistant tuberculosis

      Horter, S; Stringer, B; Reynolds, L; Shoaib, M; Kasozi, S; Casas, E C; Verputten, M; du Cros, P (BioMed Central Ltd, 2014-02-21)
      Ambulatory, community-based care for multi-drug resistant tuberculosis (MDR-TB) has been found to be effective in multiple settings with high cure rates. However, little is known about patient preferences around models of MDR-TB care. Medecins Sans Frontieres (MSF) has delivered home-based MDR-TB treatment in the rural Kitgum and Lamwo districts of northern Uganda since 2009 in collaboration with the Ministry of Health and the National TB and Leprosy Programme. We conducted a qualitative study examining the experience of patients and key stakeholders of home-based MDR-TB treatment.
    • Household screening and multidrug-resistant tuberculosis

      Cox, H; van Cutsem, G; Burnet Institute for Medical Research and Public Health, Centre for Population Health, Melbourne, Australia; Médecins Sans Frontières, Cape Town, South Africa (2010-12-09)
      Of the estimated half a million people who develop multidrug resistant (MDR) tuberculosis each year, less than 7% are diagnosed and only 1 in 5 of these have access to eff ective treatment.1 To control this epidemic, dramatically increased efforts are required to scale up case detection and treatment provision. In The Lancet, Mercedes Becerra and colleagues2 report the yield of additional MDR tuberculosis diagnoses that are found by screening household contacts of index cases in Lima, Peru. This study—the largest of its kind to date—found that more than 2% of 4503 household contacts had active tuberculosis at the time the index case was diagnosed. Incident tuberculosis was also found at a rate of 1624 cases per 100 000 person-years over 4 years follow-up. These results support recommendations for active screening of household contacts of people with MDR tuberculosis,3 and provide valuable lessons for other programmes striving to improve case detection and to reduce community transmission of MDR tuberculosis.
    • 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)
    • "I Can Also Serve as an Inspiration": A Qualitative Study of the TB&Me Blogging Experience and Its Role in MDR-TB Treatment

      Horter, S; Stringer, B; Venis, S; du Cros, P (Public Library of Science, 2014-09-24)
      In 2011, Médecins Sans Frontières (MSF) established a blogging project, "TB&Me," to enable patients with multidrug-resistant tuberculosis (MDR-TB) to share their experiences. By September 2012, 13 MDR-TB patients had blogged, either directly or with assistance, from the UK, Australia, Philippines, Swaziland, Central African Republic, Uganda, South Africa, India, and Armenia. Due to the lack of research on the potential for social media to support MDR-TB treatment and the innovative nature of the blog, we decided to conduct a qualitative study to examine patient and staff experiences. Our aim was to identify potential risks and benefits associated with blogging to enable us to determine whether social media had a role to play in supporting patients with MDR-TB.