Abstract
HIV and tuberculosis (TB) often occur together with each exacerbating the other. Improvements in vertical transmission prevention has reduced the number of HIV-infected children being born and early antiretroviral therapy (ART) protects against tuberculosis. However, with delayed HIV diagnosis, HIV-infected infants often present with tuberculosis co-infection. The number of HIV exposed uninfected children has increased and these infants have high exposure to TB and may be more immunologically vulnerable due to HIV exposure in utero. Bacillus Calmette-Guérin (BCG) immunization shortly after birth is essential for preventing severe TB in infancy. With early infant HIV diagnosis and ART, disseminated BCG is no longer an issue. TB prevention therapy should be implemented for contacts of a source case and for all HIV-infected individuals over a year of age. Although infection can be identified through skin tests or interferon gamma release assays, the non-availability of these tests should not preclude prevention therapy, once active TB has been excluded. Therapeutic options have moved from isoniazid only for 6–9 months to shorter regimens. Prevention therapy after exposure to a source case with resistant TB should also be implemented, but should not prevent pivotal prevention trials already under way. A microbiological diagnosis for TB remains the gold standard because of increasing drug resistance. Antiretroviral therapy for rifampicin co-treatment requires adaptation for those on lopinavir-ritonavir, which requires super-boosting with additional ritonavir. For those with drug resistant TB, the main problems are identification and overlapping toxicity between antiretroviral and anti-TB therapy. In spite of renewed focus and improved interventions, infants are still vulnerable to TB.
Highlights
Since the identification of Mycobacterium tuberculosis (M.tb) as the cause of tuberculosis (TB) in March 1882 [1], M.tb remains one of most lethal human pathogens, causing more deaths than any other infectious agent [2]
In a South African study from the late 1990’s that predated availability of antiretroviral therapy (ART), nearly half (48.9%) of children hospitalized with pulmonary TB were Human Immunodeficiency Virus (HIV)+
TB and TB meningitis in vaccines infants altered cell-mediated immunity, including impaired T-cell maturation, and hypo- and hyper-responsive T-cell activation [22]. These immune changes may be mediated by fetal HIV exposure as they are absent in mothers established on ART at conception [24]
Summary
Tuberculosis (TB) is a leading cause of morbidity and mortality in both adults and children across the globe. The causative agent, Mycobacterium tuberculosis (M.tb), causes more deaths than any other infectious agent. Human Immunodeficiency Virus (HIV) coinfection contributes greatly to the global burden of TB, in sub Saharan Africa, where the prevalence of both diseases is high. The ambitious goal to eradicate TB, as set by the World Health Organization (WHO), faces multiple challenges, for childhood TB. In the HIV/TB co-infected child, the risk of infection and disease is increased, diagnosis is challenging, and treatment involves high medication burden and complex drug interactions. National TB programs highlighting early identification of childhood case contacts, adequate and appropriate preventative therapy, novel strategies, and advancements in TB diagnostics and drug therapy, and early initiation of antiretroviral therapy are all positive steps toward achieving this goal
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