Early outcomes of MDR-TB treatment in a high HIV-prevalence setting in Southern Africa
Kwonjune J Seung, David B Omatayo, Salmaan Keshavjee, Jennifer J Furin, Paul E Farmer, Hind Satti, Kwonjune J Seung, David B Omatayo, Salmaan Keshavjee, Jennifer J Furin, Paul E Farmer, Hind Satti
Abstract
Background: Little is known about treatment of multidrug-resistant tuberculosis (MDR-TB) in high HIV-prevalence settings such as sub-Saharan Africa.
Methodology/principal findings: We did a retrospective analysis of early outcomes of the first cohort of patients registered in the Lesotho national MDR-TB program between July 21, 2007 and April 21, 2008. Seventy-six patients were included for analysis. Patient follow-up ended when an outcome was recorded, or on October 21, 2008 for those still on treatment. Fifty-six patients (74%) were infected with HIV; the median CD4 cell count was 184 cells/microl (range 5-824 cells/microl). By the end of the follow-up period, study patients had been followed for a median of 252 days (range 12-451 days). Twenty-two patients (29%) had died, and 52 patients (68%) were alive and in treatment. In patients who did not die, culture conversion was documented in 52/54 patients (96%). One patient had defaulted, and one patient had transferred out. Death occurred after a median of 66 days in treatment (range 12-374 days).
Conclusions/significance: In a region where clinicians and program managers are increasingly confronted by drug-resistant tuberculosis, this report provides sobering evidence of the difficulty of MDR-TB treatment in high HIV-prevalence settings. In Lesotho, an innovative community-based treatment model that involved social and nutritional support, twice-daily directly observed treatment and early empiric use of second-line TB drugs was successful in reducing mortality of MDR-TB patients. Further research is urgently needed to improve MDR-TB treatment outcomes in high HIV-prevalence settings.
Conflict of interest statement
Competing Interests: The authors have declared that no competing interests exist.
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References
- Wells CD, Cegielski JP, Nelson LJ, Laserson KF, Holtz TH, et al. HIV infection and multidrug-resistant tuberculosis: the perfect storm. J Infect Dis. 2007;196(Suppl 1):S86–107.
- WHO/IUATLD. Geneva: World Health Organization; 2008. Anti-Tuberculosis Drug Resistance in the World: Fourth Global Report (WHO/HTM/TB/2008.394).
- Gandhi NR, Moll A, Sturm AW, Pawinski R, Govender T, et al. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet. 2006;368:1575–1580.
- Mukherjee JS, Rich ML, Socci AR, Joseph JK, Viru FA, et al. Programmes and principles in treatment of multidrug-resistant tuberculosis. Lancet. 2004;363:474–481.
- Mitnick C, Bayona J, Palacios E, Shin S, Furin J, et al. Community-based therapy for multidrug-resistant tuberculosis in Lima, Peru. N Engl J Med. 2003;348:119–128.
- Leimane V, Riekstina V, Holtz TH, Zarovska E, Skripconoka V, et al. Clinical outcome of individualised treatment of multidrug-resistant tuberculosis in Latvia: a retrospective cohort study. Lancet. 2005;365:318–326.
- Demographic and Health Survey, Lesotho. Ministry of Health and Social Welfare, Bureau of Statistics. 2004
- World Health Organization Global TB Database. Accessed May 11, 2008.
- TB and HIV Co-Infection. Ministry of Health and Social Welfare, Lesotho. 2007
- The Green Light Committee (GLC) Initiative. Accessed February 5, 2009.
- WHO. Geneva: World Health Organization; 2008. Guidelines for the Programmatic Management of Drug-resistant Tuberculosis: Emergency Update 2008 (WHO/HTM/TB/2008.402).
- Laserson KF, Thorpe LE, Leimane V, Weyer K, Mitnick CD, et al. Speaking the same language: treatment outcome definitions for multidrug-resistant tuberculosis. Int J Tuberc Lung Dis. 2005;9:640–645.
- Orenstein EW, Basu S, Shah NS, Andrews JR, Friedland GH, et al. Treatment outcomes among patients with multidrug-resistant tuberculosis: systematic review and meta-analysis. Lancet Infect Dis. 2009;9:153–161.
- Shin SS, Pasechnikov AD, Gelmanova IY, Peremitin GG, Strelis AK, et al. Treatment outcomes in an integrated civilian and prison MDR-TB treatment program in Russia. Int J Tuberc Lung Dis. 2006;10:402–408.
- Tupasi TE, Gupta R, Quelapio MI, Orillaza RB, Mira NR, et al. Feasibility and cost-effectiveness of treating multidrug-resistant tuberculosis: a cohort study in the Philippines. PLoS Med. 2006;3:e352.
- Murray J, Sonnenberg P, Shearer SC, Godfrey-Faussett P. Human immunodeficiency virus and the outcome of treatment for new and recurrent pulmonary tuberculosis in African patients. Am J Respir Crit Care Med. 1999;159:733–740.
- Nunn P, Brindle R, Carpenter L, Odhiambo J, Wasunna K, et al. Cohort study of human immunodeficiency virus infection in patients with tuberculosis in Nairobi, Kenya. Analysis of early (6-month) mortality. Am Rev Respir Dis. 1992;146:849–854.
- Harries AD, Hargreaves NJ, Gausi F, Kwanjana JH, Salaniponi FM. High early death rate in tuberculosis patients in Malawi. Int J Tuberc Lung Dis. 2001;5:1000–1005.
- Alvarez GG, Thembela BL, Muller FJ, Clinch J, Singhal N, et al. Tuberculosis at Edendale Hospital in Pietermaritzburg, Kwazulu Natal, South Africa. Int J Tuberc Lung Dis. 2004;8:1472–1478.
- Rich ML, Socci AR, Mitnick CD, Nardell EA, Becerra MC, et al. Representative drug susceptibility patterns for guiding design of retreatment regimens for MDR-TB. Int J Tuberc Lung Dis. 2006;10:290–296.
- Saravia JC, Appleton SC, Rich ML, Sarria M, Bayona J, et al. Retreatment management strategies when first-line tuberculosis therapy fails. Int J Tuberc Lung Dis. 2005;9:421–429.
- WHO . Geneva: World Health Organization; 2009. Management of MDR-TB: a field guide. A companion document to Guidelines for the Programmatic Management of Drug-resistant Tuberculosis (WHO/HTM/TB/2008.402a).
- Singh JA, Upshur R, Padayatchi N. XDR-TB in South Africa: no time for denial or complacency. PLoS Med. 2007;4:e50.
- Murphy RA. The emerging crisis of drug-resistant tuberculosis in South Africa: lessons from New York City. Clin Infect Dis. 2008;46:1729–1732.
- Basu S, Andrews JR, Poolman EM, Gandhi NR, Shah NS, et al. Prevention of nosocomial transmission of extensively drug-resistant tuberculosis in rural South African district hospitals: an epidemiological modelling study. Lancet. 2007;370:1500–1507.
- Shin S, Furin J, Bayona J, Mate K, Kim JY, et al. Community-based treatment of multidrug-resistant tuberculosis in Lima, Peru: 7 years of experience. Soc Sci Med. 2004;59:1529–1539.
- Shean KP, Willcox PA, Siwendu SN, Laserson KF, Gross L, et al. Treatment outcome and follow-up of multidrug-resistant tuberculosis patients, West Coast/Winelands, South Africa, 1992-2002. Int J Tuberc Lung Dis. 2008;12:1182–1189.
- Holtz TH, Lancaster J, Laserson KF, Wells CD, Thorpe L, et al. Risk factors associated with default from multidrug-resistant tuberculosis treatment, South Africa, 1999-2001. Int J Tuberc Lung Dis. 2006;10:649–655.
- Furin JJ, Mitnick CD, Shin SS, Bayona J, Becerra MC, et al. Occurrence of serious adverse effects in patients receiving community-based therapy for multidrug-resistant tuberculosis. Int J Tuberc Lung Dis. 2001;5:648–655.
- Shin SS, Pasechnikov AD, Gelmanova IY, Peremitin GG, Strelis AK, et al. Adverse reactions among patients being treated for MDR-TB in Tomsk, Russia. Int J Tuberc Lung Dis. 2007;11:1314–1320.
- Nathanson E, Gupta R, Huamani P, Leimane V, Pasechnikov AD, et al. Adverse events in the treatment of multidrug-resistant tuberculosis: results from the DOTS-Plus initiative. Int J Tuberc Lung Dis. 2004;8:1382–1384.
- Nunn P, Kibuga D, Gathua S, Brindle R, Imalingat A, et al. Cutaneous hypersensitivity reactions due to thiacetazone in HIV-1 seropositive patients treated for tuberculosis. Lancet. 1991;337:627–630.
- Marks DJ, Dheda K, Dawson R, Ainslie G, Miller RF. Adverse events to antituberculosis therapy: influence of HIV and antiretroviral drugs. Int J STD AIDS. 2009;20:339–345.
- Yee D, Valiquette C, Pelletier M, Parisien I, Rocher I, et al. Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis. Am J Respir Crit Care Med. 2003;167:1472–1477.
- Cegielski JP, McMurray DN. The relationship between malnutrition and tuberculosis: evidence from studies in humans and experimental animals. Int J Tuberc Lung Dis. 2004;8:286–298.
- Suttmann U, Ockenga J, Selberg O, Hoogestraat L, Deicher H, et al. Incidence and prognostic value of malnutrition and wasting in human immunodeficiency virus-infected outpatients. J Acquir Immune Defic Syndr Hum Retrovirol. 1995;8:239–246.
- Mangili A, Murman DH, Zampini AM, Wanke CA. Nutrition and HIV infection: review of weight loss and wasting in the era of highly active antiretroviral therapy from the nutrition for healthy living cohort. Clin Infect Dis. 2006;42:836–842.
Source: PubMed