Mini-symposium: Childhood TB in 2010
TB and HIV in children – advances in prevention and management

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Summary

The human immunodeficiency virus (HIV) epidemic has had a major impact on the age and gender profile of adult tuberculosis (TB) patients, resulting in increased exposure of HIV-infected and uninfected children at a very young age. Young and/or HIV-infected children are extremely vulnerable to develop severe forms of TB following recent exposure and infection. There is an urgent need to implement safe and pragmatic strategies to prevent TB in children, especially in TB endemic areas where they suffer the greatest burden of disease.

The management of TB in HIV-infected children poses multiple challenges, but recent advances in the implementation of prevention of mother to child transmission (PMTCT) strategies and HIV care of infants offer hope. These include HIV testing and access to PMTCT for all pregnant women, routine testing of all HIV exposed infants and rapid initiation of antiretroviral treatment irrespective of clinical or immunological disease staging. In addition, careful scrutiny for TB exposure should occur at every health care visit, with provision of isoniazid preventive therapy (IPT) following each documented exposure event. Knowing the HIV infection status of child TB suspects is essential to optimize case management. Although multiple difficulties remain, recent advances demonstrate that the management of children with TB and/or HIV can be vastly improved by well focused interventions using readily available resources.

Section snippets

Epidemiologic considerations

World Health Organization (WHO) figures suggests that the global tuberculosis (TB) incidence has stabilized since 2004, with many regions on track to meet Millenium Developmental Goal targets set for 2015.1 However, TB-disease rates remain at unprecedented high levels in countries with high prevalence of concomitant human immunodeficiency virus (HIV) and/or drug resistant TB epidemics.1 Despite progress in HIV awareness and care, huge programmatic gaps remain. The most recent WHO report

Epidemic control

The most effective means to prevent recurrent M. tuberculosis infection in children is to “close the tap”, by improving general epidemic control. Early detection and rapid cure of infectious cases is essential to limit ongoing transmission, which sustains the epidemic [Table 1]. This explains why the WHO incorporated intensified case finding, together with infection control and isoniazid preventive therapy (IPT), as key components of the “three I's” prevention strategy.20 Population based

Vaccination

M. bovis BCG is an attenuated live vaccine, developed by Calmette and Guerin in the 1920's. It offers highly variable protection against adult-type pulmonary TB, with no evidence of epidemiologic impact in TB endemic areas.41 However, it does offer significant protection against disseminated (miliary) disease in HIV-uninfected infants.42 Complications from BCG, apart from mild local or regional reactions, are extremely rare in immune competent children. In contrast, in HIV-infected infants the

Antiretroviral therapy

Studies in HIV-infected adults demonstrated that ART significantly reduced TB rates, with increasing benefits over time.48, 49 Immune recovery after ART reduce the risk of TB by more than 50%,the benefit being greatest with earlier HIV diagnosis and treatment.50, 51 Despite ART the TB risk remains substantially elevated compared to HIV-uninfected controls.52 Modeling suggests that starting ART at higher CD4 counts is an important public health strategy to consider in order to reduce TB

Diagnosis

The diagnosis of childhood TB presents a major challenge as specimen collection is difficult and bacteriologic confirmation is rarely achieved.58 Sputum smear microscopy is often the only diagnostic test available, but young children cannot expectorate and yields in gastric aspirates are low; 10-15% of children with probable TB.58 The yield from culture after 2-3 fasting gastric aspirate samples is 30-40%, but higher yields are possible in children with advanced disease.59 Alternative sample

Treatment

TB treatment recommendations are similar for HIV-infected and –uninfected children,32 although severely immune compromised children are at increased risk of TB relapse.67 Consideration may be given to prolonging the treatment duration from 6 months to 9 months, but benefit has not been demonstrated in a randomized controlled trial. Many studies report higher mortality in HIV-infected compared to -uninfected children with TB. This may reflect one of the following:

  • higher incidence of

Drug interactions

TB is frequently the presenting disease in children with previously undiagnosed HIV infection. According to the most recent WHO guidance, lifelong ART should be initiated as soon as possible (preferably within the first 2-8 weeks of TB therapy) in all HIV-infected individuals diagnosed with TB.68

Significant drug interactions occur between the rifamycins, especially rifampicin (RMP), and some of the non-nucleoside reverse transcriptase inhibitors (NNRTI's) and/or protease inhibitors. RMP is

Immune Reconstitution Inflammatory Syndrome (IRIS)

Transient worsening of symptoms such as fever, increasing lymphadenopathy, exacerbation of intracerebral tuberculomas, pleural effusions and even respiratory distress syndrome have been reported after the initiation of HAART in severely immunocompromised patients.75, 76 TB IRIS may present as “unmasking IRIS”, where subclinical disease becomes evident after immune reconstitution, or as “paradoxical IRIS” where symptomatic deterioration occurs despite adequate TB treatment.77 This temporary

Conclusion

The major burden of TB in HIV-infected children occurs where both diseases are common in adults. Recent advances in PMTCT implementation and HIV care of infants offer hope. These include rapid HAART initiation in all HIV-infected infants irrespective of clinical or immunological disease staging, together with careful TB exposure monitoring and IPT provision after each documented exposure event. Routine HIV testing is an essential part of the diagnostic work-up for child TB suspects, since

Conflict of interest statement

None of the authors has a conflict of interest to declare.

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