Diarrheal illness is responsible for over a quarter of all deaths in children under 5 years of age in sub-Saharan Africa and South Asia. Recent findings have pointed to the parasite Cryptosporidium spp. as a major contributor to enteric disease burden in the developing world. We assessed whether Cryptosporidium spp. interacted with any other co-occurring pathogen in the Global Enteric Multicenter Study to moderate odds of moderate-to-severe diarrhea (MSD).
We examined 32 pathogens detected in stools from 9,348 cases and 13,128 controls from The Gambia, Kenya, Mali, Mozambique, India, Bangladesh, and Pakistan. Analysis for multiplicative and additive interaction was completed using R version 3.2.1, based on calculated odds of MSD adjusted for site, age, sex, body mass index, antibiotic use, and stool consistency.
Cryptosporidium spp. was found to interact negatively with Shigella spp., with an Interaction Contrast Ratio (ICR) of 0.16 (95% CI: 0.07 to 0.37, p-value <0.0001) on the multiplicative scale, and Relative Excess Risk due to Interaction (RERI) of -9.81 (95% CI: -13.61 to -6.01, p-value <0.0001) on the additive scale. Odds of MSD for Cryptosporidium spp. co-infection with Shigella spp. are lower than odds of MSD with either organism alone. When the study population was subdivided by age or country, Shigella spp. negatively interacted with Cryptosporidium spp. on the multiplicative scale, additive scale, or both scales in the 12-23 month old age group, the 24-35 month old age group, and in the Kenyan study population. Cryptosporidium spp. also interacted negatively with adenovirus in the 6-11 month old age group, Aeromonas spp. and rotavirus in the 12-23 month old age group, atypical entero-pathogenic Escherichia coli and norovirus in Kenya, and astrovirus in Pakistan. Cryptosporidium spp. interacted positively with entero-aggregative E. coli in Mozambique, and Entamoeba histolytica in Pakistan.
To our knowledge, this is the first study to show that Cryptosporidium spp. interacts with co-infecting bacteria, viruses, or protozoa to alter enteric disease outcomes in humans. These interactions may impact the efficacy of targeted intervention strategies and should be further explored.
M. Pop, None
A. Sapkota, None