Title: Risk Factors for Emerging and Reemerging Infectious Diseases in Children
Description: This dissertation assesses the factors that lead to the emergence of infectious diseases in children, particularly the emergence of multidrug-resistant organisms (MDROs) and diarrheal pathogens in vulnerable pediatric populations. It includes three manuscripts. The initial study is a systematic review that summarized the role of antibiotic exposure on the acquisition of MDROs in children. Twenty-nine studies met the inclusion criteria and a positive association between prior antibiotic use and subsequent colonization or infection with an MDRO was identified in most studies. There were wide variations among study sites, populations, and definitions of antibiotic use and MDROs. Therefore, limited inferences could be made on which components of antibiotic exposure have the greatest impact on MDRO development. The second analysis examines the relationship between prior stay at a pediatric long-term care (LTC) facility and infection with an MDRO among hospitalized children. This study included 2,945 infections in 258,664 pediatric admissions from 2006 through 2016.

At least 1 MDRO was identified in 10% of infections. Of the 1,198 children who had previously resided in a pediatric LTC facility, only 1 child (0.08%) had an MDRO infection. However, prior receipt of pediatric LTC was associated with an increased likelihood of infection (OR 2.4, CI95 1.66 – 3.43), C. difficile infection (OR 2.57, CI95 1.26 – 5.25), days of antibiotic use (OR 1.01, CI95 1.01 – 1.02), length of stay (OR 1.01, CI95 1.01 – 1.01), and death (OR 4.38, CI95 2.93 – 6.55). The concluding study evaluates the association between animals living in or near the home and diarrheal disease in children. This research is a secondary analysis of the Global Enteric Multicenter Study case control study, which investigated the epidemiology of diarrheal illness in children <5 in sub-Saharan Africa and south Asia. Of 9,439 cases and 13,128 controls, 87% had ≥1 animal in their home. In a multivariable analysis adjusting for exclusive breastfeeding, water source, sanitation facility, number of children <5 years in the household, and wealth index, any animal on a child’s compound decreased the odds of diarrhea by 33% (aOR 0.66, CI95 0.59 – 0.74).

However, children with diarrhea who had an animal present were not more likely to have a positive stool culture. Overall, the three studies provide a thorough analysis of several factors associated with the infectious disease emergence in children, particularly as related to MDROs and diarrheal disease. Environmental characteristics, including antibiotic use and interaction with animals, were shown to be important factors for emergent infectious disease across diverse settings. The development of pediatric infection prevention interventions should take into consideration environmental risk factors in order to effectively mitigate the risks posed infectious disease emergence.