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Background   Campylobacter  is one of the main causes of gastroenteritis worldwide. Most of the current knowledge about the epidemiology of this food-borne infection concerns two species,  C .  coli  and  C .  jejuni . Recent studies conducted in developing countries and using novel diagnostic techniques have generated evidence of the increasing burden and importance of other  Campylobacter  species, i.e. non- C .  coli/jejuni . We performed a nested case-control study to compare the prevalence of  C .  coli/jejuni  and other  Campylobacter  in children with clinical dysentery and severe diarrhea as well as without diarrhea to better understand the clinical importance of infections with  Campylobacter  species other than  C .  coli/jejuni .    Methodology/Principal findings  Our nested case-control study of 439 stool samples included dysenteric stools, stools collected during severe diarrhea episodes, and asymptomatic stools which were systematically selected to be representative of clinical phenotypes from 9,160 stools collected during a birth cohort study of 201 children followed until two years of age. Other  Campylobacter  accounted for 76.4% of the 216  Campylobacter  detections by qPCR and were more prevalent than  C .  coli/jejuni  across all clinical groups. Other  Campylobacter  were also more prevalent than  C .  coli/jejuni  across all age groups, with older children bearing a higher burden of other  Campylobacter . Biomarkers of intestinal inflammation and injury (methylene blue, fecal occult test, myeloperoxidase or MPO) showed a strong association with dysentery, but mixed results with infection. MPO levels were generally higher among children infected with  C .  coli/jejuni , but  Shigella -infected children suffering from dysentery recorded the highest levels (26,224 ng/mL); the lowest levels (10,625 ng/mL) were among asymptomatic children infected with other  Campylobacter . Adjusting for age, sex, and  Shigella  infection, dysentery was significantly associated with  C .  coli/jejuni  but not with other  Campylobacter , whereas severe diarrhea was significantly associated with both  C .  coli/jejuni  and other  Campylobacter . Compared to asymptomatic children, children suffering from dysentery had a 14.6 odds of  C .  coli/jejuni  infection (p-value < 0.001, 95% CI 5.5–38.7) but were equally likely to have other  Campylobacter  infections–odds ratio of 1.3 (0.434, 0.7–2.4). Children suffering from severe diarrhea were more likely than asymptomatic children to test positive for both  C .  coli/jejuni  and other  Campylobacter –OR of 2.8 (0.034, 1.1–7.1) and 1.9 (0.018, 1.1–3.1), respectively. Compared to the  Campylobacter -free group, the odds of all diarrhea given  C .  coli/jejuni  infection and other  Campylobacter  infection were 8.8 (<0.001, 3.0–25.7) and 2.4 (0.002, 1.4–4.2), respectively. Eliminating other  Campylobacter  in this population would eliminate 24.9% of the diarrhea cases, which is almost twice the population attributable fraction of 15.1% due to  C .  coli/jejuni .    Conclusions/Significance  Eighty-seven percent of the dysentery and 59.5% of the severe diarrhea samples were positive for  Campylobacter ,  Shigella , or both, emphasizing the importance of targeting these pathogens to limit the impact of dysentery and severe diarrhea in children. Notably, the higher prevalence of other  Campylobacter  compared to  C .  coli/jejuni , their increasing burden during early childhood, and their association with severe diarrhea highlight the importance of these non- C .  coli/jejuni Campylobacter  species and suggest a need to clarify their importance in the etiology of clinical disease across different epidemiological contexts.

The other Campylobacters: Not innocent bystanders in endemic diarrhea and dysentery in children in low-income settings