In this article, we highlight technological pediatric TB research advances across the TB care cascade; discuss recently completed or ongoing work in adults and corresponding significant research gaps for children; and offer recommendations and opportunities to increase investments and accelerate pediatric TB R&D.

An association between rotavirus vaccination and intussusception has been documented in post-licensure studies in some countries. We evaluated the risk of intussusception associated with monovalent rotavirus vaccine (Rotavac) administered at 6, 10 and 14 weeks of age in India. Active prospective surveillance for intussusception was conducted at 22 hospitals across 16 states from April 2016 through September 2017. Data on demography, clinical features and vaccination were documented. Age-adjusted relative incidence for 1–7, 8–21, and 1–21 days after rotavirus vaccination in children aged 28–364 days at intussusception onset was estimated using the self-controlled case-series (SCCS) method. Only Brighton Collaboration level 1 cases were included. Out of 670 children aged 2–23 months with intussusception, 311 (46.4%) children were aged 28–364 days with confirmed vaccination status. Out of these, 52 intussusception cases with confirmed receipt of RVV were included in the SCCS analysis. No intussusception case was observed within 21 days of dose 1. Only one case occurred during 8–21 days after the dose 2. Post-dose 3, two cases in 1–7 days and 7 cases during 8–21 days period were observed. There was no increased risk of intussusception during 1–7 days after the doses 1 and 2 (zero cases observed) or dose 3 (relative incidence [RI], 1.71 [95% confidence interval {CI} 0.0–5.11]). Similarly, no increased risk during 8–21 days after the dose 1 (zero cases observed), dose 2 (RI, 0.71 [95% CI, 0.0–3.28]) or dose 3 (RI, 2.52 [95% CI, 0.78–5.61]). The results were similar for 1–21 day periods after the doses separately or pooled. The risk of intussusception during the first 21 days after any dose of rotavirus vaccine (Rotavac) was not higher among the Indian infants than the background risk, based on limited SCCS analysis of 52 children.

Intussusception has been linked with rotavirus vaccine (RVV) as a rare adverse reaction. In view of limited background data on intussusception in India and in preparation for RVV introduction, a surveillance network was established to document the epidemiology of intussusception cases in Indian children. Intussusception in children 2-23 months were documented at 19 nationally representative sentinel hospitals through a retrospective surveillance for 69 months (July 2010 to March 2016). For each case clinical, hospital course, treatment and outcome data were collected. Among the 1588 intussusception cases, 54.5% were from South India and 66.3% were boys. The median age was 8 months (IQR 6, 12) with 34.6% aged 2-6 months. Seasonal variation with higher cases were documented during March-June period. The most common symptoms and signs were vomiting (63.4%), bloody stool (49.1%), abdominal pain (46.9%) and excessive crying (42.8%). The classical triad (vomiting, abdominal pain, and blood in stools) was observed in 25.6% cases. 96.4% cases were diagnosed by ultrasound with ileocolic location as the commonest (85.3%). Management was done by reduction (50.8%) and surgery (41.1%) and only 1% of the patients' died. 91.1% cases met Brighton criteria level 1 and 3.3% Level 2. Between 2010 and 2015, the case load and case ratio increased across all regions. Intussusception cases have occurred in children across all parts of the country, with low case fatality in the settings studied. The progressive rise cases could indicate an increasing awareness and availability of diagnostic facilities.

Background: India introduced rotavirus vaccines (RVV, monovalent, Rotavac™ and pentavalent, Rotasiil™) in April 2016 with 6, 10 and 14 weeks schedule and expanded countrywide in phases. We describe the epidemiology of intussusception among children aged 2–23 months in India. Methods: The prospective surveillance at 19 nationally representative sentinel hospitals from four regions recruited children with intussusception from April 2016 to September 2017. Data on sociodemography, immunization, clinical, treatment and outcome were collected. Along with descriptive analysis, key parameters between four regions were compared using Chi-Square/Fisher’s exact/Mann–Whitney U/Kruskal-Wallis tests. The pre- and post-RVV periods were compared to estimate the risk ratios. Results: Six hundred twenty-one children with intussusception from South (n = 262), East (n = 190), North (n = 136) and West (n = 33) regions were recruited. Majority (n = 465, 74.8%) were infants (40.0% aged 4–7 months) with median age 8 months (IQR 5, 13 months), predominantly males (n = 408, 65.7%) and half (n = 311, 50.0%) occurred during March–June months. A shorter interval between weaning and intussusception was observed for ragi based food (median 1 month, IQR 0–4.2 months) compared to rice (median 4 months, IQR 1–9 months) and wheat (median 3 months, IQR 1–7 months) based food (p < 0.01). Abdominal pain or excessive crying (82.8%), vomiting (72.6%), and bloody stool (58.1%) were the leading symptoms. Classical triad (abdominal pain, vomiting and bloody stool) was observed in 34.8% cases (24.4 to 45.8% across regions). 95.3% of the cases were diagnosed by ultrasound. 49.3% (10.5 to 82.4% across regions) cases were managed by reduction, 39.5% (11.5 to 71.1% across regions) cases underwent surgery and 11.1% spontaneously resolved. Eleven (1.8%) cases died. 89.1% cases met Brighton criteria level 1 and 7.6% met Level 2. RVV was received by 12 cases within 1–21 days prior to intussusception. No increase in case load (RR = 0.44; 95% CI 0.22–1.18) or case ratio (RR = 0.5; 95% CI 0.3–1.2) was observed after RVV introduction in select sites. Conclusions: Intussusception cases were observed across all sites, although there were variations in cases, presentation and mode of management. The high case load age coincided with age of the RVV third dose. The association with ragi based weaning food in intussusception needs further evaluation.

In the continued battle against one of the oldest enemies known to mankind, Mycobacterium tuberculosis (MTB), the emergence of drug resistance to antituberculosis drugs among children poses multiple challenges for early detection and treatment. Molecular diagnostics and newer drugs like bedaquiline and delamanid have strengthened the armamentarium and helped design convenient, safe, and child-friendly therapeutic regimens against drug-resistant tuberculosis (TB). Preventive strategies like treatment of TB infection among children living in close contact with patients with drug-resistant TB and effective vaccines against TB are currently in the investigative stages of development and implementation. In addition to the implementation of recent novel diagnostics and treatment modalities, effective psychosocial and nutritional support, as well as dedicated monitoring for compliance and adverse effects, are crucial determinants for successful treatment outcomes in these children.