Mini-symposium: Childhood TB in 2010TB and HIV in children – advances in prevention and management
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:
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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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Cited by (33)
Viral–bacterial interactions within hosts
2023, Molecular Medical Microbiology, Third EditionTUBERCULOSIS IN CHILDREN. HOW IS IT DIAGNOSED?
2017, Revista Medica Clinica Las CondesRecommendations Concerning the Therapeutic Approach to Immunocompromised Children with Tuberculosis
2016, Clinical TherapeuticsCitation Excerpt :HIV infection increases the risk of active TB in patients with latent TB infection and those recently exposed to TB. Only ~10% of people infected with TB in the general population actually develop the disease, whereas this risk is 20 to 30 times higher in HIV-infected patients.35 A prospective, laboratory-guided surveillance study conducted in South Africa found that the incidence of disseminated TB was 240 cases per 100,000 among HIV-infected children (95% CI, 89–433/100,000) versus 14 cases per 100,000 (95% CI, 10–18/100,000) among uninfected children of the same age.36
Towards early inclusion of children in tuberculosis drugs trials: A consensus statement
2015, The Lancet Infectious DiseasesCitation Excerpt :Underdiagnosis (and thus underreporting) is of particular concern in young children who are at greatest risk of disease progression after exposure and infection, and in whom microbiological, or other diagnostic confirmation of both tuberculosis infection and disease is not straightforward.3 HIV infection increases the risk of tuberculosis disease and death, especially in the absence of antiretroviral treatment.4–10 Another concern is that the number of children with drug-resistant tuberculosis is increasing worldwide.11–16
Tuberculosis and HIV co-infection-focus on the Asia-Pacific region
2015, International Journal of Infectious DiseasesCitation Excerpt :As in adults, TB is a leading cause of death in HIV-infected children.57 Children living in HIV-affected households are at increased risk of TB exposure and infection irrespective of their own HIV status, with those who are HIV-infected being at increased risk of developing TB disease progression.58,59 The clinical approach to TB diagnosis is similar to adults with sputum smear-negative disease, taking into account the likelihood of TB exposure, proof of M. tuberculosis infection (tuberculin skin test induration of ≥5 mm, or a positive M. tuberculosis interferon-gamma-release assay), clinical features, and chest X-ray signs suggestive of TB, as well as appropriate microbiological evaluation.59,60
HIV/AIDS in Children
2013, Manson's Tropical Diseases: Twenty-Third Edition