High Incidence of Tuberculosis among HIV-Infected Infants: Evidence from a South African Population-Based Study Highlights the Need for Improved Tuberculosis Control Strategies

Clinical Infectious Diseases, Jan 2009

Background. There are limited population-based estimates of tuberculosis incidence among human immunodeficiency virus (HIV)—infected and HIV-uninfected infants aged ⩽12 months. We aimed to estimate the population-based incidence of culture-confirmed tuberculosis among HIV-infected and HIV-uninfected infants in the Western Cape Province, South Africa. Methods. The incidences of pulmonary, extrapulmonary, and disseminated tuberculosis were estimated over a 3-year period (2004–2006) with use of prospective representative hospital surveillance data of the annual number of culture-confirmed tuberculosis cases among infants. The total number of HIV-infected and HIV-uninfected infants was calculated using population-based estimates of the total number of live infants and the annual maternal HIV prevalence and vertical HIV transmission rates. Results. There were 245 infants with culture-confirmed tuberculosis. The overall incidences of tuberculosis were 1596 cases per 100,000 population among HIV-infected infants (95% confidence interval [CI], 1151–2132 cases per 100,000 population) and 65.9 cases per 100,000 population among HIV-uninfected infants (95% CI, 56–75 cases per 100,000 population). The relative risk of culture-confirmed tuberculosis among HIV-infected infants was 24.2 (95% CI, 17–34). The incidences of disseminated tuberculosis were 240.9 cases per 100,000 population (95% CI, 89–433 cases per 100,000 population) among HIV-infected infants and 14.1 cases per 100,000 population (95% CI, 10–18 cases per 100,000 population) among HIV-uninfected infants (relative risk, 17.1; 95% CI, 6–34). Conclusions. This study indicates the magnitude of the tuberculosis disease burden among HIV-infected infants and provides population-based comparative incidence rates of tuberculosis among HIV-infected infants. This high risk of tuberculosis among HIV-infected infants is of great concern and may be attributable to an increased risk of tuberculosis exposure, increased immune-mediated tuberculosis susceptibility, and/or possible limited protective effect of bacille Calmette-Guérin vaccination. Improved tuberculosis control strategies, including maternal tuberculosis screening, contact tracing of tuberculosis-exposed infants coupled with preventive chemotherapy, and effective vaccine strategies, are needed for infants in settings where HIV infection and tuberculosis are highly endemic.

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High Incidence of Tuberculosis among HIV-Infected Infants: Evidence from a South African Population-Based Study Highlights the Need for Improved Tuberculosis Control Strategies

A. C. Hesseling 2 3 8 M. F. Cotton 1 2 T. Jennings 2 3 A. Whitelaw 0 2 7 L. F. Johnson 2 4 B. Eley 2 6 P. Roux 2 5 P. Godfrey-Faussett 2 8 H. S. Schaaf 2 3 0 National Health Laboratory Service 1 KidCru, Tygerberg Academic Hospital, Department of Paediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University , Tygerberg , South Africa 2 of Paediatrics and Child Health , Clinical Bldg., Rm. 0085 , Faculty of Health Sciences, Stellenbosch University , PO Box 19063, Tygerberg, South Africa (annekeh @sun.ac.za) 3 Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Health Sciences 4 Centre for Actuarial Research, University of Cape Town , Cape Town , South Africa 5 Department of Paediatrics, Groote Schuur Hospital 6 Paediatric Infectious Diseases Unit, Red Cross Children's Hospital and School of Child and Adolescent Health 7 Department of Medical Microbiology 8 Clinical Research Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London , United Kingdom Background. There are limited population-based estimates of tuberculosis incidence among human immunodeficiency virus (HIV)-infected and HIV-uninfected infants aged 12 months. We aimed to estimate the population-based incidence of culture-confirmed tuberculosis among HIV-infected and HIV-uninfected infants in the Western Cape Province, South Africa. Methods. The incidences of pulmonary, extrapulmonary, and disseminated tuberculosis were estimated over a 3-year period (2004-2006) with use of prospective representative hospital surveillance data of the annual number of culture-confirmed tuberculosis cases among infants. The total number of HIV-infected and HIV-uninfected infants was calculated using population-based estimates of the total number of live infants and the annual maternal HIV prevalence and vertical HIV transmission rates. Results. There were 245 infants with culture-confirmed tuberculosis. The overall incidences of tuberculosis were 1596 cases per 100,000 population among HIV-infected infants (95% confidence interval [CI], 1151-2132 cases per 100,000 population) and 65.9 cases per 100,000 population among HIV-uninfected infants (95% CI, 5675 cases per 100,000 population). The relative risk of culture-confirmed tuberculosis among HIV-infected infants was 24.2 (95% CI, 17-34). The incidences of disseminated tuberculosis were 240.9 cases per 100,000 population (95% CI, 89-433 cases per 100,000 population) among HIV-infected infants and 14.1 cases per 100,000 population (95% CI, 10-18 cases per 100,000 population) among HIV-uninfected infants (relative risk, 17.1; 95% CI, 6-34). Conclusions. This study indicates the magnitude of the tuberculosis disease burden among HIV-infected infants and provides population-based comparative incidence rates of tuberculosis among HIV-infected infants. This high risk of tuberculosis among HIV-infected infants is of great concern and may be attributable to an increased risk of tuberculosis exposure, increased immune-mediated tuberculosis susceptibility, and/or possible limited protective effect of bacille Calmette-Guerin vaccination. Improved tuberculosis control strategies, including maternal tuberculosis screening, contact tracing of tuberculosis-exposed infants coupled with preventive chemotherapy, and effective vaccine strategies, are needed for infants in settings where HIV infection and tuberculosis are highly endemic. Infants in settings where tuberculosis and HIV infection are highly endemic are at high-risk of tuberculosis-related morbidity and mortality [1]. Studies from the - prechemotherapy era indicate that, in the absence of preventive chemotherapy, up to 40% of infants who were infected with Mycobacterium tuberculosis subsequently developed tuberculosis disease. Children aged !2 years were most at risk of developing disease, and disease progression occurred mostly in the first calendar year after primary infection [24]. The incidence of infant tuberculosis is an indicator of both control of infectious tuberculosis and the effectiveness of tuberculosis prevention strategies, such as neonatal bacille Calmette-Guerin (BCG) vaccination. The Joint United Nations Program on HIV/AIDS estimated that, in 2007, 390,000470,000 children aged !15 years acquired HIV infection, mostly through mother-to-child (vertical) transmission [5]. There are few estimates comparing tuberculosis rates between HIV-uninfected and HIV-infected infants and children. The protective effect of BCG vaccination against pulmonary tuberculosis in childhood is inconsistent [6], and there is limited epidemiological evidence of any BCG-induced protective effect in HIV-infected children [7, 8]. However, there is considerable evidence for the protective efficacy of BCG vaccination against disseminated tuberculosis in HIV-uninfected infants [9]. Recent data indicate that HIV-infected infants have a substantially increased risk of serious BCG-associated (...truncated)


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A. C. Hesseling, M. F. Cotton, T. Jennings, A. Whitelaw, L. F. Johnson, B. Eley, P. Roux, P. Godfrey-Faussett, H. S. Schaaf. High Incidence of Tuberculosis among HIV-Infected Infants: Evidence from a South African Population-Based Study Highlights the Need for Improved Tuberculosis Control Strategies, Clinical Infectious Diseases, 2009, pp. 108-114, 48/1, DOI: 10.1086/595012