Ultrasound of the spleen demonstrates a diffuse coarse echogenicity with multiple hypoechoic lesions highly suggestive of microabscesses. The radiologic differential for microabscesses in the spleen includes disseminated TB, non-tuberculous mycobacterial infection (Mycobacterium avium complex), and fungal infections.

Her CD4 count was 53 cells/mm³ (2.02%). The baseline viral load was 4,170,560 RNA copies/mL. There was no known TB contact.

She was treated for community-acquired pneumonia, and responded well to therapy. She was discharged four days later in good health, with a plan to initiate her onto antiretroviral therapy (ART) in 4 weeks, once stabilised on anti-TB treatment.

Question 1: According to the World Health Organization, what clinical stage of HIV does this child fall into?

Question 2: What investigations can be sent to confirm a microbiological diagnosis of tuberculosis in this infant?

Question 3: What anti-tuberculosis regimen would you use in such a child?

Question 4: What doses of first-line anti-tuberculosis drugs are recommended for children, according to the South African TB Guidelines?

Question 5: What additional medication is warranted in such a child, and why?

Frontal chest X-ray demonstrates reticular pattern in the right middle zone, with some obscuration of the right heart border. The child is rotated in this X-ray, but there are no obvious features to suggest hilar adenopathy, i.e. no lobulated, dense masses filling the hilar points

Question 6: Why would a liver function test be warranted in this infant, despite the fact that she was not clinically jaundiced?

Discussion:

Toxicity to first-line anti-TB drugs is uncommon in clinical paediatrics, however it may be devastating if not managed appropriately [5]. Although isoniazid, rifampicin and pyrazinamide all have the potential for causing hepatocyte damage, isoniazid is the most frequently implicated agent [6]. Isoniazid is metabolised by N-acetyltransferase in the liver, and young children tend to metabolise the drug more efficiently than do older children and adults [7]. Recommended doses of isoniazid in the South African Paediatric TB Guidelines (10-15 mg/kg/day) and revised World Health Organization (WHO) Guidelines (10 mg/kg/day) is higher than those previously recommended in paediatric treatment guidance documents ( ̴5 mg/kg/day) [8].

It is expedient to do baseline liver function tests (ALT, AST) in young HIV-infected children who are on anti-TB treatment, in whom we are soon to initiate ART [9]. No baseline liver functions were done in the child reported here, and the hepatitic picture would have been missed entirely if the test was not conducted at the second hospital admission.

A positive TB blood culture in this child is reassuring of the fact that continuation of anti-TB therapy is warranted in this child. Duration of anti-TB therapy is debatable, but as isoniazid cannot be used with safety, at least 12 months of treatment is justified.

Acknowledgements

Thank-you to Dr Pedro da Silva (Braamfontein TB Laboratory) for assistance in interpreting the TB blood culture result), and Dr Nasreen Mahomed (Respiratory & Meningeal Pathogens Research Unit, ) for expertise in interpreting the radiological investigations done in this case. Ethics permissions for online publication of this case were obtained from the Chris Hani Baragwanath Medical Advisory Committee and the University of the Witwatersrand Human Research Ethics Committee (Medical)

References:

1. World Health Organization, Antiretroviral therapy for HIV infection in infants and children: towards universal access, ed. World Health Organization2010, Geneva: World Health Organization.
2. South African National Department of Health, Guidelines for the Management of Tuberculosis in Children, South African National Department of Health, Editor 2013, South African National Department of Health: Pretoria.
3. South African Department of Health, National consolidated guidelines for the prevention of mother-to-child transmission of HIV (PMTCT) and the management of HIV in children, adolescents and adults, South African Department of Health, Editor 2014, South African Department of Health: Pretoria.
4. Moore, D.P., et al., Childhood tuberculosis guidelines of the Southern African Society for Paediatric Infectious Diseases. South Afr J Epidemiol Infect, 2009. 24(3): p. 57-68.
5. Wu, S.S., et al., Isoniazid-related hepatic failure in children: a survey of liver transplantation centers. Transplantation, 2007. 84(2): p. 173-9.
6. Donald, P.R., Antituberculosis drug-induced hepatotoxicity in children. Pediatr Rep, 2011. 3(2): p. e16.
7. Schaaf, H.S., et al., Isoniazid pharmacokinetics in children treated for respiratory tuberculosis. Archives of disease in childhood, 2005. 90(6): p. 614-8.
8. Thee, S., et al., Pharmacokinetics of isoniazid, rifampin, and pyrazinamide in children younger than two years of age with tuberculosis: evidence for implementation of revised World Health Organization recommendations. Antimicrob Agents Chemother, 2011. 55(12): p. 5560-7.
9. South African National Department of Health, The South African Antiretroviral Treatment Guidelines, 2013, South African National Department of Health, Editor 2013, South African National Department of Health: Pretoria.