Clostridium difficile Infection (CDI) is the cause of substantial morbidity and mortality in the developed world. However, very little is known about the burden of CDI in sub-Saharan Africa where less antibiotic restriction, high HIV prevalence and greater impact from nosocomial infection mean the potential for a significant disease burden is great. Researchers investigated the prevalence of Clostridium difficile Toxin (CDT), assessing association with HIV, CD4 count and diarrhoea in medical in-patients in Malawi. In 206 patients tested for CDT, 28 (13.6%) were positive. No significant associations were seen with either diarrhoea or HIV. There was a non-statistically significant (p = 0.056) association between CD4 counts of <50 and CDT. The frequency and the clinical implications of CDI in both HIV positive and negative patients in sub-Saharan Africa, requires further assessment.