Tuberculosis and HIV-An Update on the "Cursed Duet" in Children

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.

Keywords: HIV; TB/HIV co-infection; TB/HIV co-therapy; childhood TB; tuberculosis.

Figure 1

Algorithm for the evaluation and treatment of a newborn infant with TB +/- HIV exposure. (1) Early identification of HIV exposure (if not ascertained in the antenatal period) with maternal testing. Confirmation of transmission with PCR testing of the infant at 4–6 weeks. However, birth testing may be beneficial to early identification and treatment of perinatally infected infants. (2) Identify the risk of TB in the mother: thorough history, contact exposure, symptom screening, clinical examination, chest x-ray, sputum microscopy, culture and sensitivity and GeneXpert, if risk of miliary TB or TB meningitis is suspected: lumbar puncture, as necessary, initiate appropriate TB therapy in the mother. If the mother is diagnosed with TB, the placenta should be evaluated with histologic staining (including acid-fast bacilli) and tissue culture. Consider whether mother could have resistant TB. (3) If the newborn is HIV exposed, initiate prevention of mother to child prophylaxis: twice daily Zidovudine with added daily Nevirapine or Nevirapine + Lamivudine if there is a high risk of transmission. (4) The TB exposed newborn may present with symptoms or be asymptomatic. Clinical observation and examination for symptoms and signs forms part of the diagnostic process. Other investigations: chest radiograph, abdominal ultrasound, Tuberculin skin testing, specimens for TB culture and GeneXpert. (5) TB therapy for drug susceptible TB in the neonate: 4 months of daily: Rifampicin 15 mg/kg, Isoniazid 10 mg/kg, Pyrazinamide 35 mg/kg, Ethambutol 20 mg/kg, followed by 2 months of daily doses: Rifampicin 15 mg/kg, Isoniazid 10 mg/kg. (6) Initiate ART consisting of: Zidovudine, Lamivudine and Nevirapine or Raltegravir. (7) If confirmed or suspected drug sensitive TB disease is excluded, Isoniazid prophylaxis at 10 mg/kg should commence and continue for 6 months. Close monitoring and follow-up is required to identify TB symptoms and signs. (8) Initiate ART consisting of: Zidovudine, Lamivudine and Nevirapine or Raltegravir.

Figure 2

Algorithm for the evaluation and treatment of a child exposed to a TB source case. (1) Health promotion of testing all children in contact with an adult TB source case is important. Children ≤5 years of age are at high risk for TB disease. (2) History includes that of the source case: drug susceptible or drug resistant TB, compliance on TB treatment, first or second episode of TB. History of the child includes weight loss, loss of playfulness, coughing, fever, drenching night sweats. (3) Anthropometry is important in the clinical examination of all children. Respiratory signs may be non-specific and other HIV related respiratory conditions should be considered e.g., non-TB bacterial pneumonia, lymphocytic interstitial pneumonitis. (4) Children with a history of a TB contact may be asymptomatic, or present with non-specific symptoms for example, growth faltering. (5) These include a tuberculin skin test, chest radiograph and IGRA. In the symptomatic child, respiratory or other sampling for GeneXpert and microscopy (including acid-fast bacilli), culture and sensitivity, serum culture. Consider lumbar puncture and neuro imaging if suspicion of military TB or TB meningitis. Specialized tests indicated if extra pulmonary TB is suspected e.g., abdominal ultrasound, cardiac echo etc. (6) Uncomplicated TB: 4 months of daily Rifampicin 15 mg/kg, Isoniazid 10 mg/kg, Pyrazinamide 35 mg/kg followed by 2 months of daily Rifampicin 15 mg/kg, Isoniazid 10 mg/kg. In HIV+ children or complicated TB: 4 months of daily Rifampicin 15 mg/kg, Isoniazid 10 mg/kg, Pyrazinamide 35 mg/kg, Ethambutol 20 mg/kg, followed by 2 months of daily doses: Rifampicin 15 mg/kg, Isoniazid 10 mg/kg. (7) If TB has been clinically excluded, 6 months of Isoniazid prophylaxis is recommended. An alternative is 12 weekly doses of Isoniazid and Rifapentine.