Pediatric acute gastroenteritis associated with adenovirus 40/41 in low-income and middle-income countries.

PURPOSE OF REVIEW: To review the roles of enteric adenovirus types 40 and 41 and nonenteric adenoviruses in the global burden of pediatric diarrhea. RECENT FINDINGS: Large studies using highly sensitive, type-specific molecular diagnostics have demonstrated a substantial and previously under-estimated burden of pediatric diarrheal disease because of enteric infections with adenovirus types 40/41. However, the true epidemiology of adenovirus 40/41 remains incompletely understood. Similarly, additional adenovirus types may also be implicated as agents of community-acquired pediatric gastroenteritis but current data are too limited to elucidate their epidemiological role(s), if any. SUMMARY: Efforts at global diarrhea control in low-income and middle-income countries will require combating pediatric gastroenteritis because of enteric adenovirus infections. Future research in these settings using type-specific molecular diagnostics or strain genotyping to fully characterize the epidemiology of adenovirus 40/41 infections, identify non-40/41 adenoviruses significantly associated with gastroenteritis, and develop vaccines effective at preventing adenovirus diarrhea is warranted.

The effect of increased inoculum on oral rotavirus vaccine take among infants in Dhaka, Bangladesh: A double-blind, parallel group, randomized, controlled trial.

BACKGROUND: Oral, live-attenuated rotavirus vaccines suffer from impaired immunogenicity and efficacy in low-income countries. Increasing the inoculum of vaccine might improve vaccine response, but this approach has been inadequately explored in low-income countries. METHODS: We performed a double-blind, parallel group, randomized controlled trial from June 2017 through June 2018 in the urban Mirpur slum of Dhaka, Bangladesh to compare vaccine take (primary outcome) among healthy infants randomized to receive either the standard dose or double the standard dose of oral Rotarix (GlaxoSmithKline) vaccine at 6 and 10 weeks of life. Infants with congenital malformations, birth or enrollment weight <2000 gm, known immunocompromising condition, enrollment in another vaccine trial, or other household member enrolled in the study were excluded. Infants were randomized using random permuted blocks. Vaccine take was defined as detection of post-vaccination fecal vaccine shedding by real-time reverse transcription polymerase chain reaction with sequence confirmation or plasma rotavirus-specific immunoglobulin A (RV-IgA) seroconversion 4 weeks following the second dose. RESULTS: 220 infants were enrolled and randomized (110 per group). 97 standard-dose and 92 high-dose infants completed the study per-protocol. For the primary outcome, no significant difference was observed between groups: vaccine take occurred in 62 (67%) high-dose infants versus 69 (71%) standard-dose infants (RR 0.92, 95% CI 0.67-1.24). However, in post-hoc analysis, children with confirmed vaccine replication had significantly increased RV-IgA responses, independent of the intervention. No significant adverse events related to study participation were detected. CONCLUSIONS: Administration of double the standard dose of an oral, live-attenuated rotavirus vaccine (Rotarix) did not improve vaccine take among infants in urban Dhaka, Bangladesh. However, improved immunogenicity in children with vaccine replication irrespective of initial inoculum provides further evidence for the need to promote in-host replication and improved gut health to improve oral vaccine response in low-income settings. ClinicalTrials.gov: NCT02992197.