Clinical relevance of enteropathogen co-infections in preschool children—a population-based repeated cross-sectional study

Abstract

Objectives: This study aimed to (i) determine risk factors for enteropathogen co-infections, (ii) determine whether enteropathogen co-infections influence gastroenteritis risk, and (iii) determine whether enteropathogen co-infection occurred randomly in preschool children. Methods: A monthly-repeated cross-sectional survey in Dutch children aged 0e48 months was conducted during October 2012 to October 2014. A total of 981 stool samples were collected along with questionnaires collecting data on gastrointestinal symptoms and potential risk factors; 822 samples were successfully tested for 19 enteropathogens using real-time multiplex PCRs. Logistic regression analysis assessed co-infections in relation to gastroenteritis and potential risk factors. Results: In all, 598/822 (72.7%) stool samples tested positive for at least one enteropathogen, of which 290 (48.5%) were positive for two or more enteropathogens. Risk factors for two or more enteropathogen co-infections were young age (<12 months, OR 1.9, 95% CI 1.1e3.3; 13e36 months, OR 1.7, 95% CI 1.1e2.5, versus 37e48 months), day-care attendance (OR 1.8, 95% CI 1.3e2.5), households with three or more children versus those with one child (OR 1.7, 95% CI 1.1e2.8). Stool samples collected in spring less often had two or more enteropathogens versus summer (OR 0.4, 95% CI 0.2e0.7). Food allergy was a risk factor for three or more enteropathogen co-infections (OR 3.2, 95% CI 1.1e8.9). The frequency of co-infection was higher than expected for norovirus GI/norovirus GII, Clostridium difficile/norovirus GI, C. difficile/ rotavirus, astrovirus/Dientamoeba fragilis, atypical enteropathogenic Escherichia coli/adenovirus, typical enteropathogenic E. coli/adenovirus, and enteroaggregative E. coli/astrovirus. No co-infection was associated with increased gastroenteritis risk. Conclusions: Risk factors for enteropathogen co-infections were identified and specific enteropathogens co-occurred significantly more often than expected by chance. Enteropathogen co-infections were not associated with increased gastroenteritis risk, calling into question their clinical relevance in preschool children. R.

Enteric Viral Co-Infections: Pathogenesis and Perspective

“…The first several years of life are then a particularly dramatic period of co-infection, and the simultaneous detection of multiple enteropathogens is common, both associated with AGE and even in the absence of symptoms. As an example of prevalence in early life, a cohort of Dutch infants had at least one enteropathogen, including eukaryotic viruses and bacterial pathogens, detected in~73% of samples tested, and of these, nearly half had two distinct pathogens detected [25]. Similarly, a longitudinal study conducted in two healthy British infants during their first year of life showed that a variety of human viruses, including AdV, AstV, RV, and multiple enteroviruses, were present during this period [26].…”

“…Risk factors for acquiring enteric co-infections include young age, daycare attendance, and households with more than three children [25], as well as contaminated drinking water and poor sanitation [27]. Children from high income regions often exhibit lower rates of co-infection than those from lower income regions.…”

“…Overall, these studies support that in healthy children and adults experiencing AGE episodes, between~3-50% may have more than one viral pathogen present. Some reports indicate that RV co-infections, at least in healthy children, are not associated with greater symptom severity than single RV infection [25,27], while another reported that co-infections with NoV may lead to more severe AGE with enhanced comorbidities, such as vomiting and fever, compared to NoV alone [94]. Further clinical studies exploring the effects of co-infection on symptom severity are needed to better clarify the relative contribution of co-infection to disease outcomes.…”

Epidemiology and Genetic Characterization of Classical Human Astrovirus Infection in Shanghai, 2015–2016

“…Infection of classic HAstVs usually causes mild symptoms and has been implicated in gastroenteritis outbreaks indoors, such as in daycare centers and schools ( Pankovics et al, 2011 ; Tan et al, 2019 ). Mixed infections of HAstVs with rotavirus, norovirus, and adenovirus are common ( Chhabra et al, 2013 ; Li et al, 2016 ; Liu et al, 2016 ; Andersson et al, 2018 ; Pijnacker et al, 2019 ). In susceptible individuals, including pediatric patients, older adults, and the immunocompromised hosts, HAstVs, especially non-classic human astroviruses (HAstV-VA/HMO and HAstV-MLB), may infect the central nervous system with severe clinical consequences ( Fremond et al, 2015 ; Cordey et al, 2016 ; Lum et al, 2016 ; Sato et al, 2016 ).…”

Evaluation of viral co-infections among patients with community-associated Clostridioides difficile infection

“…In other countries, the prevalence of co-infection with a gastrointestinal pathogen among patients with CDI have varied from 34% to 67% [14][15][16]. In a multicenter study on community-acquired gastroenteritis conducted in 10 European countries, the proportion of CDI patients with co-infection was highest in those <5 years of age [14].…”