• 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.
    • Compliance with Cotrimoxazole Prophylaxis for the Prevention of Opportunistic Infections in HIV-Positive Tuberculosis Patients in Thyolo District, Malawi.

      Zachariah, R; Harries, A D; Arendt, V; Wennig, R; Schneider, S; Spielmann M P; Panarotto, E; Gomani, P; Salaniponi, F M L; Medecins sans Frontieres-Luxembourg, Thyolo District, Malawi. msflblantyre@malawi.net (International Union Against TB and Lung Disease, 2001-09)
      OBJECTIVE: To verify compliance with cotrimoxazole prophylaxis in human immunodeficiency virus (HIV) infected tuberculosis (TB) patients during the continuation phase of anti-tuberculosis treatment, and to assess the sensitivity, specificity and positive predictive values of verbal verification and pill counts as methods of checking compliance. DESIGN: Cross-sectional study. METHODS: Cotrimoxazole compliance was assessed in a cohort of TB patients who were attending four TB follow-up centres during the continuation phase of anti-TB treatment between months 4 and 6. Verbal verification of drug intake, physical verification of pill count balance, and urine trimethoprim detection by gas chromatography and mass spectrometry were used for assessing compliance. RESULTS: Using urine trimethoprim detection as the gold standard for compliance, trimethoprim was detected in 82 (94%) of 87 patients in the cohort. Verbal verification of cotrimoxazole intake and objective pill count balances showed high sensitivity and positive predictive values compared with the gold standard of urine trimethoprim detection. CONCLUSIONS: In a rural district in Malawi, compliance with cotrimoxazole as an adjunct to anti-tuberculosis treatment in HIV-infected TB patients was good, and can be assessed simply and practically by verbal verification and pill counts.
    • Cotrimoxazole prophylaxis in HIV-infected individuals after completing anti-tuberculosis treatment in Thyolo, Malawi.

      Zachariah, R; Spielmann M P; Harries, A D; Gomani, P; Bakali, E; Médecins Sans Frontières-Luxembourg, Thyolo, Thyolo District, Malawi. zachariah@internet.lu (2002-12)
      SETTING: Thyolo, rural southern Malawi. OBJECTIVES: To determine 1) the proportion who continue with cotrimoxazole prophylaxis for the prevention of opportunistic infections, and 2) the reasons for continuing or stopping prophylaxis, in human immunodeficiency virus (HIV) infected individuals with tuberculosis (TB) who complete anti-tuberculosis treatment. DESIGN: A cross-sectional study. METHODS: A questionnaire study of all HIV-infected TB patients who had been registered over a 3-month period to receive anti-tuberculosis treatment and cotrimoxazole prophylaxis and who had completed antituberculosis treatment 3-6 months earlier. RESULTS: Of 82 HIV-infected individuals who were alive at the time of interview, 76 (93%) were continuing with cotrimoxazole and wished to do so indefinitely. The most common reason for continuing the drug was to prevent illness associated with HIV, while the most common reason for stopping was long distances to the health facility. Ninety-six percent of patients received cotrimoxazole free of charge from a health centre. Of those who wished to continue indefinitely, the majority (63%) could not afford to pay for the drug. CONCLUSIONS: In a rural setting, the great majority of HIV-infected individuals continued with cotrimoxazole after completing anti-tuberculosis treatment. Making the drug available and providing it free of charge is essential if it is to remain accessible for longer term prevention.
    • Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis.

      Blanc, F-X; Sok, T; Laureillard, D; Borand, L; Rekacewicz, C; Nerrienet, E; Madec, Y; Marcy, O; Chan, S; Prak, N; et al. (2011-10-20)
      Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy.
    • 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.
    • 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.
    • The looming epidemic of diabetes-associated tuberculosis: learning lessons from HIV-associated tuberculosis

      Harries, A D; Lin, Y; Satyanarayana, S; Lönnroth, K; Li, L; Wilson, N; Chauhan, L S; Zachariah, R; Baker, M A; Jeon, C Y; et al. (International Union Against Tuberculosis and Lung Disease, 2011-11-01)
      The prevalence of diabetes mellitus is increasing at a dramatic rate, and countries in Asia, particularly India and China, will bear the brunt of this epidemic. Persons with diabetes have a significantly increased risk of active tuberculosis (TB), which is two to three times higher than in persons without diabetes. In this article, we argue that the epidemiological interactions and the effects on clinical presentation and treatment resulting from the interaction between diabetes and TB are similar to those observed for human immunodeficiency virus (HIV) and TB. The lessons learned from approaches to reduce the dual burden of HIV and TB, and especially the modes of screening for the two diseases, can be adapted and applied to the screening, diagnosis, treatment and prevention of diabetes and TB. The new World Health Organization (WHO) and The Union Collaborative Framework for care and control of TB and diabetes has many similarities to the WHO Policy on Collaborative Activities to reduce the dual burden of TB and HIV, and aims to guide policy makers and implementers on how to move forward and combat this looming dual epidemic. The response to the growing HIV-associated TB epidemic in the 1980s and 1990s was slow and uncoordinated, despite clearly articulated warnings about the scale of the forthcoming problem. We must not make the same mistake with diabetes and TB. The Framework provides a template for action, and it is now up to donors, policy makers and implementers to apply the recommendations in the field and to 'learn by doing'.
    • Low uptake of antiretroviral therapy after admission with human immunodeficiency virus and tuberculosis in KwaZulu-Natal, South Africa.

      Murphy, R A; Sunpath, H; Taha, B; Kappagoda, S; Maphasa, K T M; Kuritzkes, D R; Smeaton, L; Doctors Without Borders USA, New York, USA; McCord Hospital, South Africa; Harvard Medical School, Massachusetts, USA; Division of Infectious Disease and Geographic Medicine, California, USA; Zoe-Life, South Africa; Section of Retroviral Therapeutics, Massachusetts, USA; Centre for Biostatistics in AIDS Research, Massachusetts, USA (2010-07-01)
      A prospective cohort study was conducted among human immunodeficiency virus (HIV) infected in-patients with tuberculosis (TB) or other opportunistic infections (OIs) in South Africa to estimate subsequent antiretroviral therapy (ART) uptake and survival.
    • Moderate to severe malnutrition in patients with tuberculosis is a risk factor associated with early death.

      Zachariah, R; Spielmann M P; Harries, A D; Salaniponi, F M L; Médecins Sans Frontières-Luxembourg, Thyolo District, Malawi. zachariah@internet.lu (Elsevier, 2008-02-07)
      A study was conducted in new patients registered with tuberculosis (TB) in a rural district of Malawi to determine (i) the prevalence of malnutrition on admission and (ii) the association between malnutrition and early mortality (defined as death within the first 4 weeks of treatment). There were 1181 patients with TB (576 men and 605 women), whose overall rate of infection with human immunodeficiency virus (HIV) was 80%. 673 TB patients (57%) were malnourished on admission (body mass index [BMI] < 18.5 kg/m2). There were 259 patients (22%) with mild malnutrition (BMI 17.0-18.4 kg/m2), 168 (14%) with moderate malnutrition (BMI 16.0-16.9 kg/m2) and 246 (21%) with severe malnutrition (BMI < 15.9 kg/m2). 95 patients (8%) died during the first 4 weeks. Significant risk factors for early mortality included increasing degrees of malnutrition, age > 35 years, and HIV seropositivity. Among all the 1181 patients, 10.9% of the 414 patients with moderate to severe malnutrition died in the first 4 weeks compared with 6.5% of the 767 patients with normal to mild malnutrition (odds ratio 1.8, 95% confidence interval 1.1-2.7). In patients with TB, BMI < 17.0 kg/m2 is associated with an increased risk of early death.