Impact of the Antiretroviral Treatment Program on the Burden of Hospitalization for Culture-Confirmed Tuberculosis in South African Children: A Time-Series Analysis.

1Department of Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, South Africa. 2Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases & Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, University of the Witwatersrand, South Africa. 3City of Hamilton Public Health Services, Hamilton, Ontario, Canada. 4Mycobacteriology Referral Laboratory, National Health Laboratory Service, Johannesburg, South Africa. 5National Institute for Communicable Diseases: a division of National Health Laboratory Service, Centre for Tuberculosis, Sandringham, South Africa.
The Pediatric Infectious Disease Journal (Impact Factor: 2.72). 03/2013; 32(9). DOI: 10.1097/INF.0b013e31828d9aa4
Source: PubMed


The HIV epidemic increased the burden of tuberculosis (TB) in sub-Saharan Africa. We evaluated the impact that scaling-up of the public-funded antiretroviral treatment (ART) program had on incidence of hospitalization for culture-confirmed and overall-TB in HIV-infected and HIV-uninfected children from 2005 to 2009.

The study was undertaken in Soweto, South Africa, where ART coverage of HIV-infected children increased from 43% in 2005 to 84% by 2009. Trends in incidence of hospitalization for clinically diagnosed and culture-confirmed TB in children 3 months to <15 years of age, identified through laboratory and electronic databases, were analyzed by comparing crude incidence and regression analysis.

The incidence (per 100,000) of culture-confirmed TB declined by 63.1% from 2005 (69.8) compared with 2009 (25.8; P < 0.0001). This included a 70.6% reduction between 2005 and 2009 among HIV-infected children (incidence: 1566.3 versus 460.7, respectively; P < 0.0001) and 41.3% decrease in HIV-uninfected children (18.7 versus 11.0, respectively; P = 0.0003). The month-by-month rate of decline of culture-confirmed TB was 2.3% in HIV-infected and 1.1% in HIV-uninfected children over the study period. The residual burden of TB remained 42-fold greater in HIV-infected children, 78% of whom were severely immune compromised, compared with HIV-uninfected children by 2009.

Increase in ART coverage was associated with significant decline in TB hospitalizations in HIV-infected children. This reduction may also in part have been due to reduced Mycobacterium tuberculosis transmission resulting from increased ART access among HIV-infected adults, which may have contributed to the reduction of culture-confirmed TB in HIV-uninfected children.

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    • "In particular, the possible increased susceptibility to developing TB following influenza epidemics, may lend itself to underlying immune suppression which subsequently increases the susceptibility to developing IPD in the South African context, especially with its high burden of HIV and TB co-infection. Previous studies conducted in high HIV prevalent settings have reported an increased burden of IPD and PTB disease in HIV-infected children [1], [29]. Furthermore, almost two thirds of hospitalized PTB and IPD cases with a known HIV status were HIV-infected in our study period. "
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    ABSTRACT: The seasonal variability in hospitalization for tuberculosis may in part relate to super-imposed bacterial or predisposing respiratory viral infections. We aimed to study the temporal association between hospitalization for culture-confirmed pulmonary tuberculosis (PTB), invasive pneumococcal disease (IPD) and influenza virus epidemics in South African children. We undertook a retrospective analysis which examined seasonal trends, from 2005 to 2008, for hospitalization for culture-confirmed PTB and IPD among children in relation to the influenza epidemics in Soweto, South Africa. Original time-series of the influenza virus epidemics and hospitalization rates for PTB and IPD were decomposed into three components: a trend cycle component, a seasonal component and an irregular component using the X-11 seasonal adjustment method. To compare the seasonality amongst the three series, the trend and irregular components were removed and only seasonal components examined. Across the study period, the influenza virus epidemics peaked during May to July (winter) months, which was closely followed by an increase in the incidence of hospitalization for IPD (August to October) and PTB (August to November). Within- and between-year temporal changes associated with childhood TB hospitalization may in part be driven by factors which influence temporal changes in pneumococcal disease, including potential variability in the severity of influenza virus epidemics in temperate climates. The dynamics of the interplay between the host and these infectious agents appears to be complex and multifactorial.
    Full-text · Article · Mar 2014 · PLoS ONE
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    • "However in 2009 the incidence of culture confirmed TB, was still 42-fold times higher in HIV positive compared to HIV negative children (460.7/100,000 vs. 11.0/100,000). Over three quarters of co-infected children were severely immunocompromised [58]. Over 40% decline of TB incidence was also observed in HIV negative children which maybe in part due to increased ART coverage in adults and the associated decreased TB transmission. "
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    ABSTRACT: HIV is the top and tuberculosis is the second leading cause of death from infectious disease worldwide, with an estimated 8.7 million incident cases of tuberculosis and 2.5 million new HIV infections annually. The World Health Organization estimates that HIV prevalence among children with tuberculosis, in countries with moderate to high prevalence, ranges from 10 to 60%. The mechanisms promoting susceptibility of people with HIV to tuberculosis disease are incompletely understood, being likely caused by multifactorial processes. Paediatric tuberculosis and HIV have overlapping clinical manifestations, which could lead to missed or late diagnosis. Although every effort should be made to obtain a microbiologically-confirmed diagnosis in children with tuberculosis, in reality this may only be achieved in a minority, reflecting their paucibacillary nature and the difficulties in obtain samples. Rapid polymerase chain reaction tests, such as Xpert MTB/RIF assay, are increasingly used in children. The use of less or non invasive methods of sample collection, such as naso-pharyngeal aspirates and stool samples for a polymerase chain reaction-based diagnostic test tests and mycobacterial cultures is promising technique in HIV negative and HIV positive children. Anti-tuberculosis treatment should be started immediately at diagnosis with a four drug regimen, irrespective of the disease severity. Moreover, tuberculosis disease in an HIV infected child is considered to be a clinical indication for initiation of antiretroviral treatment. The World Health Organization recommends starting antiretroviral treatment in children as soon as anti-tuberculosis treatment is tolerated and within 2- 8 weeks after initiating it. The treatment of choice depends on the child’s age and availability of age-appropriate formulations, and potential drug interactions and resistance. Treatment of multi-drug resistant tuberculosis in HIV-infected children follows same principles as for HIV uninfected children. There are conflicting results on effectiveness of isoniazid preventive therapy in reducing incidence of tuberculosis disease in children with HIV. Conclusion Data on HIV/TB co-infection in children are still lacking. There are on-going large clinical trials on the prevention and treatment of TB/HIV infection in children that hopefully will help to guide an evidence-based clinical practice in both resource-rich and resource-limited settings.
    Full-text · Article · Jan 2014 · BMC Infectious Diseases
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    ABSTRACT: Tuberculosis continues to be a major global health problem, causing an estimated 8.8 million new cases and 1.45 million deaths annually. New drugs in the 1940s made it possible to beat the disease, and consequently, the number of cases reduced drastically. Fast-forward a few decades, drugresistant strains of varied virulence are reported consistently, disease is again on the rise and the treatment has not kept pace. Tuberculosis is the leading cause of death among HIV-infected persons in many resource-constrained settings however, it is curable and preventable. The unprecedented growth of the tuberculosis epidemic in Africa is attributable to several factors, the most important being the HIV epidemic. Analysis of molecular-based data have shown diverse genetic backgrounds among both drug-sensitive and MDR TB isolates in Africa presumably due to underlying genetic and environmental differences.
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