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Zoonotic pathogens make up an important and increasing number of emerging and reemerging infectious diseases of humans worldwide. It has been documented that rodents serve as hosts and reservoirs of over 60 zoonotic pathogens that pose significant challenges to human health. The Mnisi community area in Bushbuckridge Municipality, Mpumalanga Province, South Africa is cradled in the heart of a human/livestock/wildlife interface. In this community humans, domestic animals and wildlife have perennial direct and indirect contact. Research in the area has found rodents to be common and abundant with 76% of households reported seeing rodents around their homes. Of that number 62% of the respondents saw them daily. A recent study in the area suggests that rodent-borne zoonoses may be implicated as causes of non-malarial acute febrile illness. In this study, 6.5% of acute febrile illness patients tested positive for the rodent-borne zoonotic pathogen Bartonella spp. on PCR, while 6.8% of patients showed prior exposure to Coxiella burnetti, the cause of Q fever and 2.3% to Leptospira spp. The surveillance of zoonotic pathogens in rodents in this community is thus of utmost importance as the role they play in the transmission of zoonotic pathogens to humans is unknown.