Impact of Cryptosporidium spp. interaction with co-occurring microorganisms on moderate-to-severe diarrhea in the developing world

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 identified the parasite Cryptosporidium as a contributor to enteric disease. We examined 9,348 cases and 13,128 controls from the Global Enteric Multicenter Study to assess whether Cryptosporidium interacted with co-occurring pathogens based on adjusted odds of moderate-to-severe diarrhea (MSD). Cryptosporidium was found to interact negatively with Shigella spp., with multiplicative interaction score of 0.16 (95% CI: 0.07 to 0.37, p-value=0.000), and an additive interaction score of -9.81 (95% CI: -13.61 to -6.01, p-value=0.000). Cryptosporidium also interacted negatively with Aeromonas spp., Adenovirus, Norovirus, and Astrovirus with marginal significance. Odds of MSD for Cryptosporidium co-infection with Shigella spp., Aeromonas spp., Adenovirus, Norovirus, or Astrovirus are lower than odds of MSD with either organism alone. This may reduce the efficacy of intervention strategies targeted at Cryptosporidium.