MDR-TB in Children

1. MDR-TB in Children Session 8

2. Risk of TB disease varies by age • Greatest in infants (< 4 years); • Declines slowly to nadir at 5-10 years; • Rapid increase in risk with a second peak between 20-30 years. Donald PR. Age and the epidemiology and pathogenesis of tuberculosis. Lancet 2010;375:1852-4.

3. Mortality in relation to age • Infection in children less than 4 years old progresses rapidly; • Greater risk of dissemination and extrapulmonary involvement. Wallgren A. Primary tuberculous infections in young adult life and in childhood. Am J Dis Child 1941; 61: 577-589

4. High risk of infection • TST studies in the pre-chemotherapy era (1920-1950)† • Cohorts included thousands of children and adults. • Follow-up for up to 27 years. • Infectiousness of the index case: • 60–80% of children became infected when the source case was smear-positive. • 30–40% of children became infected when the source case was smear negative. † Marais BJ, Gie RP, Schaaf HS, et al. The natural history of childhood intra-thoracic TB. Int J Tuberc Lung Dis 2004;8(4):392-402.

5. MDR-TB in Children • Difficulty of bacteriological confirmation often leads to late diagnosis of MDR-TB. • Lack of DST often leads to inadequate treatment regimens and amplification of resistance. • Contact history is important: almost all resistance in children is primary. • Empiric MDR-TB treatment should be initiated in children based on the DST of the contact.

6. High risk of infection in children who are contacts of MDR-TB patients • In 119 South African children less than 5 years of age who had contact with an adult with MDR-TB in the prior 30 months: • 24% had active TB • 51% had latent infection (TST+) • 37% had no evidence of infection Schaaf HS, Gie RP, Kennedy M, et al. Evaluation of young children in contact with adult multidrug-resistant pulmonary tuberculosis: a 30-month follow-up. Pediatrics 2002;109(5):765-71.

7. MDR-TB outcomes in pediatric patients with low HIV prevalence • 29 children treated for MDR-TB in South Africa 1994-2000: • All clinically and radiologically well at 30 months of follow-up. • 16 children treated for MDR-TB in Peru 1999-2002: • 3 cured, 1 (6%) failure/death, remaining 12 children have intermediate outcomes demonstrating favorable response. Schaaf HS, Gie RP, Kennedy M, et al. Evaluation of young children in contact with adult multidrug-resistant pulmonary tuberculosis: a 30-month follow-up. Pediatrics 2002; 109: 765-771. Mukherjee JS, Joseph JK, Rich ML, et al. Clinical and programmatic considerations in the treatment of MDR-TB in children: a series of 16 patients from Lima, Peru. Int J Tuberc Lung Dis 2003; 7: 637-644.

8. MDR-TB outcomes in pediatric patients with low HIV prevalence • 38 children treated for MDR-TB in Peru 1999-2003 (28 with culture-confirmed disease): • 32 (94%) cured, 1 (3%) failure/death, 1 (3%) LTFU, and 4 probable cures. • 20 children treated for active MDR-TB in NYC 1995-2003 (6 with culture-confirmed disease): • 16 (80%) successfully completed treatment, 1 (5%) death, 2 left NYC, 1 had incomplete record. Drobac PC, Mukherjee JS, Joseph JK, et al. Community-based therapy for children with multidrug-resistant tuberculosis. Pediatrics 2006; 117(6): 2022-9. Feja K, McNelley E, Tran CS, Burzynski J, Saiman L. Management of pediatric multidrug-resistant tuberculosis and latent tuberculosis infections in New York City from 1995 to 2003. Pediatr Infect Dis J 2008; 27: 907-912.

9. Household contacts of MDR-TB patients almost always have MDR-TB • A Peru study looked at 4503 household contacts of 693 MDR-TB and XDR-TB index patients: • 117 (2.6%) had active TB at the time the index patient began MDR-TB treatment; • 242 contacts developed TB during 4-year follow-up; • Of the 359 cases of active TB, 142 had DST, of whom 129 (91%) had MDR-TB. Becerra MC, Appleton SC, Franke MF, et al. Tuberculosis burden in households of patients with multidrug-resistant and extensively drug-resistant tuberculosis: a retrospective cohort study. Lancet 2011; 377: 147-52.

10. MDR-TB outcomes in pediatric patients with high HIV prevalence • 19 children treated for MDR-TB in Lesotho • 74% HIV co-infected • 84% had cavitary lesions or bilateral disease • 10 (53%) were smear-negative at the time of MDR-TB initiation • Outcomes for 17 who had finished treatment: • 15 (88%) completed treatment or were cured, • 2 (12%) died late in treatment from unknown causes Satti H, McLaughlin MM, Omotayo DB et al. Outcomes of comprehensive care for children empirically treated for MDR-TB in a setting of high HIV prevalence. PLoS One 2012; 7/(5): e37114.

11. Adverse effects in children Al-Dabbagh M, Lapphra K, McGloin R, et al. Drug-resistant tuberculosis: pediatric guidelines. Pediatr Infect Dis J 2011; 30(6): 501-505.

12. Recommendations • Diagnosis of MDR-TB is difficult in children: • Children have lower bacillary load; the majority of children do not have positive smears or cultures. • Uses aggressive methods such as gastric lavage and sputum induction. • New technologies may prove to have a higher yield.

13. Recommendations • Contact history is the most important: • Almost all resistance in children is primary. • Household contacts of MDR-TB patients almost always have MDR-TB. • Bacteriological confirmation should not be a barrier to initiation of treatment. • Empiric MDR-TB treatment can be initiated in children based on the DST of the contact.

14. Recommendations • MDR-TB regimens for children follow the same principles as for adults: • 4 or more effective drugs, • 18-24 months of treatment, • Pill splitting is usually necessary since there are few pediatric formulations, and • Monitor weight frequently since children grow. • Children tend to tolerate second-line TB drugs better than adults.