Timothy L McMurry1, Elizabeth T Rogawski McQuade1,2, Jie Liu2, Gagandeep Kang3, Margaret N Kosek2,4, Aldo A M Lima5, Pascal O Bessong6, Amidou Samie6, Rashidul Haque7, Estomih R Mduma8, Jose Paulo Leite9, Ladaporn Bodhidatta10, Najeeha T Iqbal11, Nicola Page12, Ireen Kiwelu13, Zulfiqar A Bhutta11, Tahmeed Ahmed7, Eric R Houpt2, James A Platts-Mills2. 1. Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA. 2. Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA. 3. Christian Medical College, Vellore, India. 4. Asociación Benéfica PRISMA, Iquitos, Peru. 5. Federal University of Ceara, Fortaleza, Brazil. 6. University of Venda, Thohoyandou, South Africa. 7. International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh. 8. Haydom Global Health Research Centre, Haydom, Tanzania. 9. Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. 10. Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand. 11. Aga Khan University, Karachi, Pakistan. 12. National Institute for Communicable Diseases, Johannesburg, South Africa. 13. Kilimanjaro Clinical Research Institute, Moshi, Tanzania.
Abstract
BACKGROUND: Prolonged enteropathogen shedding after diarrhea complicates the identification of etiology in subsequent episodes and is an important driver of pathogen transmission. A standardized approach has not been applied to estimate the duration of shedding for a wide range of pathogens. METHODS: We used a multisite birth cohort of children 0-24 months of age from whom diarrheal and monthly nondiarrheal stools were previously tested by quantitative polymerase chain reaction for 29 enteropathogens. We modeled the probability of detection of the etiologic pathogen before and after diarrhea using a log-normal accelerated failure time survival model and estimated the median duration of pathogen carriage as well as differences in subclinical pathogen carriage 60 days after diarrhea onset in comparison to a prediarrhea baseline. RESULTS: We analyzed 3247 etiologic episodes of diarrhea for the 9 pathogens with the highest attributable burdens of diarrhea. The median duration of postdiarrheal carriage varied widely by pathogen, from about 1 week for rotavirus (median, 8.1 days [95% confidence interval {CI}, 6.2-9.6]) to >1 month for Cryptosporidium (39.5 days [95% CI, 30.6-49.0]). The largest increases in subclinical pathogen carriage before and after diarrhea were seen for Cryptosporidium (prevalence difference between 30 days prior and 60 days after diarrhea onset, 0.30 [95% CI, .23-.39]) and Shigella (prevalence difference, 0.21 [95% CI, .16-.27]). CONCLUSIONS: Postdiarrheal shedding was widely variable between pathogens, with strikingly prolonged shedding seen for Cryptosporidium and Shigella. Targeted antimicrobial therapy and vaccination for these pathogens may have a relatively large impact on transmission.
BACKGROUND: Prolonged enteropathogen shedding after diarrhea complicates the identification of etiology in subsequent episodes and is an important driver of pathogen transmission. A standardized approach has not been applied to estimate the duration of shedding for a wide range of pathogens. METHODS: We used a multisite birth cohort of children 0-24 months of age from whom diarrheal and monthly nondiarrheal stools were previously tested by quantitative polymerase chain reaction for 29 enteropathogens. We modeled the probability of detection of the etiologic pathogen before and after diarrhea using a log-normal accelerated failure time survival model and estimated the median duration of pathogen carriage as well as differences in subclinical pathogen carriage 60 days after diarrhea onset in comparison to a prediarrhea baseline. RESULTS: We analyzed 3247 etiologic episodes of diarrhea for the 9 pathogens with the highest attributable burdens of diarrhea. The median duration of postdiarrheal carriage varied widely by pathogen, from about 1 week for rotavirus (median, 8.1 days [95% confidence interval {CI}, 6.2-9.6]) to >1 month for Cryptosporidium (39.5 days [95% CI, 30.6-49.0]). The largest increases in subclinical pathogen carriage before and after diarrhea were seen for Cryptosporidium (prevalence difference between 30 days prior and 60 days after diarrhea onset, 0.30 [95% CI, .23-.39]) and Shigella (prevalence difference, 0.21 [95% CI, .16-.27]). CONCLUSIONS: Postdiarrheal shedding was widely variable between pathogens, with strikingly prolonged shedding seen for Cryptosporidium and Shigella. Targeted antimicrobial therapy and vaccination for these pathogens may have a relatively large impact on transmission.
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Authors: Elizabeth T Rogawski McQuade; Stephanie A Brennhofer; Sarah E Elwood; Timothy L McMurry; Joseph A Lewnard; Estomih R Mduma; Sanjaya Shrestha; Najeeha Iqbal; Pascal O Bessong; Gagandeep Kang; Margaret Kosek; Aldo A M Lima; Tahmeed Ahmed; Jie Liu; Eric R Houpt; James A Platts-Mills Journal: Proc Natl Acad Sci U S A Date: 2022-08-29 Impact factor: 12.779