MDR-TB in Children
Session 8
1
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.
USAID TB CARE II PROJECT
Donald PR. Age and the epidemiology and pathogenesis of tuberculosis. Lancet
2010;375:1852-4.
Mortality in relation to age
• Infection in children less
than 4 years old progresses
rapidly;
• Greater risk of dissemination
and extrapulmonary
involvement.
Age
(years)
Number
Mortality
0-1
39
36.9%
1-3
64
15.6%
3-7
225
4.4%
7-16
125
0.8%
Wallgren A. Primary tuberculous infections in young adult life and in childhood. Am J Dis Child 1941;
61: 577-589
USAID TB CARE II PROJECT
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.
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.
USAID TB CARE II PROJECT
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.
USAID TB CARE II PROJECT
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.
USAID TB CARE II PROJECT
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.
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 MDRTB 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.
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.
USAID TB CARE II PROJECT
Adverse effects in children
Adverse effects
Incidence in
children (%)
Potential causative agents
Hearing loss
7–9%
Km, Amk, Cm
Renal toxicity
3%
Km, Amk, Cm
12 – 50 %
H, Z, Eto, fluoroquinolones, PAS,
macrolides, amoxicillin/clavulanate
Hepatotoxicity
9%
Z, H, R, PAS, Eto, FQs, macrolides
Hypothyroidism
6–9%
Eto, PAS
Psychiatric effects
6 – 11 %
Cs, FQs, thioamides
Skin manifestations
3–8%
H, R, fluoroquinolones, Cs, Eto, E,
clofazimine, amoxicillin/clavulanate
Arthralgia, arthritis
0.7 – 4.5 %
Gastrointestinal symptoms
Fluoroquinolones, Z
Blurring of vision
9%
E, linezolid
Electrolyte abnormalities
3%
Km, Amk, Cm
Al-Dabbagh M, Lapphra K, McGloin R, et al. Drug-resistant tuberculosis: pediatric guidelines. Pediatr Infect Dis J 2011; 30(6): 501-505.
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.
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.
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.
USAID TB CARE II PROJECT