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The clinical burden of tuberculosis among human immunodeficiency virus-infected children in western Kenya and the impact of combination antiretroviral treatment
Global Health Sciences Literature Digest
Published February 3, 2010
Journal Article

Braitstein P, Nyandiko W, Vreeman R, et al. The clinical burden of tuberculosis among human immunodeficiency virus-infected children in western Kenya and the impact of combination antiretroviral treatment. Pediatr Infect Dis J. 2009 May 15.

In Context

Co-infection with HIV and tuberculosis (TB) poses a serious public health problem in sub-Saharan Africa. Tuberculosis is the leading cause of death among HIV-infected persons worldwide.(1, 2) In children, HIV infection increases their likelihood of TB exposure and risk of developing active disease. Although treatable, a definitive diagnosis of TB by identification of Mycobacterium tuberculosis in culture is limited among children in sub-Saharan Africa because infected children do not always have a large burden of organisms, techniques to obtain specimens are invasive and require highly trained personnel, and tools for culture are not readily available.(3, 4, 5) Staining of sputum, the most common diagnostic method in this setting, is hampered by the difficulty of obtaining specimens in children. As such, data on the burden of disease in this population are limited.

Objectives

  1. to describe the clinical burden of pediatric TB diagnosed in an HIV-infected population in sub-Saharan Africa;
  2. to describe the social and clinical factors associated with a TB diagnosis; and
  3. to describe the effect of combination antiretroviral treatment (cART) on the probability of being diagnosed with TB among these HIV-infected children

Setting

Urban and rural HIV care clinics in and near Eldoret, Kenya

Study Design

Prospective cohort

Participants

HIV-infected children aged 0-13 years enrolled at one of the study clinics between December 2001 and January 2007 who had at least one follow-up visit.

Outcome

TB diagnosis or initiation of anti-tuberculin treatment (excluding prophylaxis)

Methods

The data for this analysis come from clinical records of pediatric patients seen at the Academic Model Providing Access to Healthcare (AMPATH) clinics. HIV-infected patients are screened for TB at enrollment by symptom review, physical examination, and chest radiograph. Diagnosis of TB is done using the Kenneth-Jones scoring system. Included in the analysis were age, gender, the child's orphan status at enrollment (having lost one or both parents vs. having lost none), weight-for-height at enrollment, whether the child had ever attended school at the time of enrollment, CD4% closest to enrollment, the use of isoniazid prophylaxis, and whether the child was attending an urban or a rural clinic. Also analyzed was having compared with not having initiated cART prior to TB diagnosis. Severe immune suppression is defined for children aged ≤18 months as a CD4% of <25%; aged >18 months but ≤5 years as a CD4% of <20%; and aged ≥ 5 years as ≤15%.

Results

There were 6535 HIV-infected children included in the analysis with a median age at enrollment of 1.0 year (interquartile range [IQR], 0.2-4.6). There were 234 (3.6%) children diagnosed with TB at enrollment. The factors associated with diagnosis of TB at enrollment were orphanhood (46.4% vs. 22.5%, P<0.001); having attended school (55.7% vs. 24.4%, P<0.001); having an HIV-infected sibling (5.3% vs. 2.9%, P<0.008); having severely low weight-for-height (33.0% vs. 18.5%, P<0.001), being older (median 5.5 vs. 1.0 years, P<0.001); and having a lower median CD4% at or near enrollment in all age categories, although this factor was not always statistically significant due to the low number of subjects. In multivariable analysis, factors independently associated with diagnosis of TB at enrollment were having ever been in school (adjusted odds ratio [AOR]: 3.27, 95% confidence interval [CI]: 2.21-4.84); being severely immune suppressed (AOR: 2.06, 95% CI: 1.44-2.95), being an orphan (AOR: 1.70, 95% CI: 1.17-2.46), and being of severely low weight-for-height (AOR: 1.61, 95% CI: 1.34-1.94).

There were 797 new TB diagnoses and 765 had time-to-event information and 4368 child-years (CY) of follow-up (incidence rate of 17.5 (16.3-18.8)/100 CY). The incidence rate was higher in months 1 to 2 after enrollment at 355 (321.1-392.3)/100 CY, compared with 46 (40.1-52.8)/100 CY, during months 3 to 6, and 4.7 (4.0 -5.4), after the sixth month.

Independent risk factors for incident TB included being severely immune-suppressed at enrollment (adjusted hazard ratio [AHR]: 4.44, 95% CI: 3.62-5.44), having ever attended school (AHR: 2.65, 95% CI: 2.15-3.25), being an orphan (AHR: 1.57, 95% CI: 1.28 -1.92), being severely low weight-for-height at enrollment (AHR: 1.46, 95% CI: 1.32-1.62), and attending an urban clinic (AHR: 1.39, 95% CI: 1.16 -1.67). The use of cART reduced the risk of incident TB by more than 80% (AHR: 0.15, 95% CI: 0.12-0.20).

Conclusions

These data suggest a high rate of TB diagnosis among HIV-infected children, with severe immune suppression, school attendance, orphan status, very low weight-for-height, and attending an urban clinic being key risk factors. The use of combination antiretroviral treatment significantly reduces the risk of TB infection in HIV-infected children.

Quality Rating

This is a very good study. The strengths are the completeness of data, the large sample, and sufficient follow-up. The outcome measures were unbiased. The only limitation is that information on representativeness was not included.

Programmatic Implications

This study identified several modifiable factors related to TB infection among HIV-infected children. The decreased risk of TB infection with ART is probably the most important. Continued efforts to diagnose and treat HIV and TB in children and adults should remain a very high programmatic priority. Clearly, treating TB and HIV in adults can have a major impact on reducing disease burden in children.

References

  1. Tindyebwa D, Kayita J, Musoke P, et al; African Network for the Care of Children Affected by AIDS (ANECCA), eds. Handbook on Paediatric AIDS in Africa. Kampala, Uganda: Family Health International; 2005;124-132. Abstract not available.
  2. Raviglione MC, Snider DE Jr, Kochi A. Global epidemiology of tuberculosis. Morbidity and mortality of a worldwide epidemic. JAMA. 1995;273:220-226.
  3. Marais BJ, Gie RP, Schaaf HS, et al. Childhood pulmonary tuberculosis: old wisdom and new challenges. Am J Respir Crit Care Med. 2006;173:1078-1090.
  4. Marais BJ, Hesseling AC, Gie RP, et al. The bacteriologic yield in children with intrathoracic tuberculosis. Clin Infect Dis. 2006;42:e69-e71.
  5. Frieden T, ed. Toman's Tuberculosis: Case Detection, Treatment, and Monitoring - Questions and Answers. Geneva: World Health Organization; 2002. Abstract not available.