Drug-Resistant Tuberculosis Among Children: A Systematic Review and Meta-Analysis

Abstract

Background: Drug-resistant tuberculosis (DR-TB), especially multidrug-resistant tuberculosis (MDR-TB) is a public health threat. Little is known about estimates of different profiles and rates of DR-TB among children globally. Methods: We did a systematic review and meta-analysis of observational studies reporting DR-TB among children by searching Embase, PubMed, and Scopus databases from January 1, 2000 to October 1, 2020. Publications reporting more than 60 children with bacteriological confirmed tuberculosis and phenotypical drug susceptibility testing (DST) results were included. Pooled proportions of MDR-TB and sub-analysis by age subgroups, regions, economical levels were performed. Results: We identified 4,063 studies, of which 37 were included. Of 23,652 pediatric TB patients, the proportions of DR-TB, MDR-TB, mono-resistant TB, polydrug resistant TB, extensively drug-resistant TB were 13.59% (1,964/14,453), 3.72% (881/23,652), 6.07% (529/8,719), 1.61% (119/7,361), 0.44% (30/6,763), respectively. The pooled proportion of MDR-TB among 23,652 children of 37 studies was 3.7% (95% CI, 3.5-4.0%). Rate of MDR-TB was much lower in high-income countries (1.8%) than that in lower-middle-income countries (6.3%) and upper-middle-income countries (7.3%). More specifically, the rates of MDR-TB were 1.7% in USA, 1.7% in UK, 2.9% in India, 6.0% in South Africa, 9.8% in China, respectively. Conclusions: The burden of DR-TB remains high in children, and there are potential associations between rates of pediatric MDR-TB and national economical levels. More interventions on child TB cases in low-income countries may be urgently needed in future.

Keywords: children; drug resistance; meta-analysis; national economic levels; tuberculosis.

Figure 1

Flow chart for study selection. TB, tuberculosis.

Figure 2

Geographic distribution. (A) the rates of MDR-TB in each country; (B) the number of pediatric TB cases with drug susceptibility results from each country. TB, tuberculosis; MDR-TB, multidrug resistant tuberculosis.

Figure 3

Forest plot depicting the pooled proportion of multidrug-resistant tuberculosis in children. MDR-TB, multidrug resistant tuberculosis; Horizontal lines represent the 95% CIs around the point estimates for each study and the gray shaded areas are proportional to the weight given to each study.

Figure 4

Forest plots for multidrug-resistant tuberculosis ratios from 37 studies in different age subgroups. MDR-TB, multidrug resistant tuberculosis; Horizontal lines represent the 95% CIs around the point estimates for each study and the gray shaded areas are proportional to the weight given to each study.

Figure 5

Forest plots for multidrug-resistant tuberculosis ratios in different continents. MDR-TB, multidrug resistant tuberculosis; Horizontal lines represent the 95% CIs around the point estimates for each study and the gray shaded areas are proportional to the weight given to each study.

Figure 6

Forest plots for multidrug-resistant tuberculosis ratios in different country. MDR-TB, multidrug resistant tuberculosis; Horizontal lines represent the 95% CIs around the point estimates for each study and the gray shaded areas are proportional to the weight given to each study.

Figure 7

Forest plots for multidrug-resistant tuberculosis ratios in lower-middle-income, upper-middle-income, high-income countries. MDR-TB, multidrug resistant tuberculosis; Horizontal lines represent the 95% CIs around the point estimates for each study and the gray shaded areas are proportional to the weight given to each study.