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ABSTRACT Enterotoxigenic E. coli (ETEC) and salmonellae are among the major pathogens associated with diarrhea in piglets, weaning pigs and humans. Uganda is an emerging pig producer in Africa and these pathogens could be of importance, particularly to farmers with low socioeconomic indicators. However, the occurrence and epidemiology of these infections in pigs in Uganda is not known, therefore there are no control strategies in place. This cross-sectional study was conducted from 2011 to 2013 to characterize pig production and understand epidemiology of ETEC and salmonellae in pig production systems in Gulu and Soroti districts in northern and eastern Uganda, respectively. Data were collected through questionnaire surveys and analyses of fecal and tissue samples from piglets, weaners and adult pigs. The pig herds studied were identified using snowball method. Pig production in Gulu and Soroti districts was largely smallholder, practiced by farmers who kept on average 3 adult pigs and 7 to 8 suckling piglets and/or 5 weaners. In a majority of the households (67%, n = 96) adult pigs and weaners were tethered but the piglets left to roam, and natural breeding of sows with a shared boar was the most common practice (88%). In a majority of the households (60%), women provided much of the labor, but only in 23% of the households did women own and make decisions on the pigs reared. Diarrhea was a common sign of disease in piglets and weaners in 38% of the households. Diarrhea observed on piglets and weaners during data collection was associated with Salmonella infection (p=0.008). At individual level, the prevalence of Salmonella spp. was 12.2% in Gulu and 11.9% in Soroti, and a total prevalence of 12% (n= 465). At the herd level, the prevalence of Salmonella spp. was 43% in Gulu and 34 % in Soroti, and a total herd prevalence of 39% (n=93). The recovered salmonellae were highly diverse (20 serovars from 56 pigs). The serovars investigated were highly resistant to the antimicrobials - sulfamethoxazole, trimethoprim and streptomycin that are commonly used in humans and livestock in Uganda. However, “intensive” method of pig management versus “tethering and roaming” (p= 0.016, OR = 0.11; 95% CI 0.02, 0.64) or “intensive” method versus “semi-intensive” method (p= 0.048, OR = 0.12; 95% CI 0.01, 0.96) was protective of the piglets and weaners against Salmonella infection. Diarrhea attributed to ETEC infections, as observed from post-mortem and other laboratory examinations, was reported. Genes for two adhesins, F4 and AIDA-I, were detected in E. coli from diarrheic and non-diarrheic piglets, with F4 being the most prevalent. Genes for other adhesins (F5, F6, F18 and F41) were not detected. The most predominant toxin gene in E. coli from diarrheic piglets was for STb, detected from seven out of 18 diarrheic piglets. However, the gene for LT was not detected. The ETEC isolates from seven diarrheic piglets and one weaner were non-hemolytic and of the sero-groups O138, O139, O45 or non-identifiable. In addition TGEV- and PRCV-positive pigs from northern Uganda were reported. In conclusion, the smallholder farmers in the study area should be sensitize to adopt practices that reduce the magnitude of Salmonella and ETEC infections such as “intensive” piggery, improved nutrition, sanitation, biosecurity and the introduction of ETEC adhesin-based vaccines. The involvement of women should strongly be considered when disseminating information on disease control since they take care of the pigs most of the time. However, this study was limited to two districts and among smallholder farmers. There is a need to conduct similar studies in other parts of Uganda and among large scale pig producers. Some of the diarrheic piglets and weaners tested negative for Salmonella and ETEC, suggesting that there are also other causes of diarrhea that should be investigated. This study was cross-sectional and therefore, longitudinal studies should be carried out, especially in large scale systems to estimate disease incidence and loss incurred due to these diarrheal diseases. There is also a need to investigate the possible involvement of humans in the epidemiology of Salmonella antimicrobial resistance.