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1 MDR-TB in Children Session 8. USAID TB CARE II PROJECT Risk of TB disease varies by age Greatest in infants (< 4 years); Declines slowly to nadir at.

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Presentation on theme: "1 MDR-TB in Children Session 8. USAID TB CARE II PROJECT Risk of TB disease varies by age Greatest in infants (< 4 years); Declines slowly to nadir at."— Presentation transcript:

1 1 MDR-TB in Children Session 8

2 USAID TB CARE II PROJECT 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 years. Donald PR. Age and the epidemiology and pathogenesis of tuberculosis. Lancet 2010;375:

3 USAID TB CARE II PROJECT Wallgren A. Primary tuberculous infections in young adult life and in childhood. Am J Dis Child 1941; 61: Mortality in relation to age Infection in children less than 4 years old progresses rapidly; Greater risk of dissemination and extrapulmonary involvement. Age (years) NumberMortality % % % %

4 USAID TB CARE II PROJECT High risk of infection TST studies in the pre-chemotherapy era ( ) † –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):

5 USAID TB CARE II PROJECT 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 USAID TB CARE II PROJECT 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): 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

7 USAID TB CARE II PROJECT MDR-TB outcomes in pediatric patients with low HIV prevalence 29 children treated for MDR-TB in South Africa : –All clinically and radiologically well at 30 months of follow-up. 16 children treated for MDR-TB in Peru : –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: 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:

8 USAID TB CARE II PROJECT MDR-TB outcomes in pediatric patients with low HIV prevalence 38 children treated for MDR-TB in Peru (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 (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): 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 Pediatr Infect Dis J 2008; 27:

9 USAID TB CARE II PROJECT 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:

10 USAID TB CARE II PROJECT 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 USAID TB CARE II PROJECT 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): Adverse effects Incidence in children (%) Potential causative agents Hearing loss7 – 9 %Km, Amk, Cm Renal toxicity3 %Km, Amk, Cm Gastrointestinal symptoms12 – 50 %H, Z, Eto, fluoroquinolones, PAS, macrolides, amoxicillin/clavulanate Hepatotoxicity9 %Z, H, R, PAS, Eto, FQs, macrolides Hypothyroidism6 – 9 %Eto, PAS Psychiatric effects6 – 11 %Cs, FQs, thioamides Skin manifestations3 – 8 %H, R, fluoroquinolones, Cs, Eto, E, clofazimine, amoxicillin/clavulanate Arthralgia, arthritis0.7 – 4.5 %Fluoroquinolones, Z Blurring of vision9 %E, linezolid Electrolyte abnormalities3 %Km, Amk, Cm

12 USAID TB CARE II PROJECT 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 USAID TB CARE II PROJECT 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 USAID TB CARE II PROJECT 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.


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