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Clostridium difficile infections in Africa C. difficile pathogenesis C. difficile epidemiology CDI in young children CDI in infants C. difficile co-infection A B S T R A C TBackground: Diarrhea causes significant morbidity and mortality among children worldwide. Regions most affected by diarrhea include Sub-Saharan Africa and Southeast Asia, where antibiotics are in common use and can make children more vulnerable to Clostridium difficile and pathogens that are not affected by these drugs. Indeed, C. difficile is a major diarrhea-associated pathogen and poses a significant threat to vulnerable and immunocompromised populations. Yet, little is known about the role and epidemiology of C. difficile in diarrhea-associated illness among young children. As a result, C. difficile is often neglected in regions such as Sub-Saharan Africa that are most impacted by childhood diarrhea. The purpose of this study was to establish the frequency of C. difficile in young children (<5 years) with diarrhea. Methods: Children presenting with diarrhea at a national hospital in Kenya from 2015 to 2018 were enrolled consecutively. Following informed consent by a parent or legal guardian, stool samples were obtained from the children and demographic data were collected. The stools were examined for the presence of four common pathogens known to cause diarrhea: C. difficile, rotavirus, Cryptosporidium parvum, and Giardia lamblia. C. difficile was verified by toxigenic culture and PCR. The presence of C. parvum and/or G. lamblia was determined using the ImmunoCard STAT! Crypto/Giardia Rapid assay. Rotavirus was detected by ELISA. Results: The study population comprised 157 children; 62.4% were male and 37.6% were female and their average age was 12.4 months. Of the 157 stool specimens investigated, 37.6% were positive for C. difficile, 33.8% for rotavirus, 5.1% for Cryptosporidium, and 5.1% for Giardia. PCR analysis identified at least one of the C. difficile-specific -genes (tcdA, tcdB, or tcdC). Further, 57.6% of the stools had C. difficile colonies bearing a frame-shift deletion in the tcdC gene, a mutation associated with increased toxin production. The frequency of C. difficile was 32.6% in children 12 months old and increased to 46.6% in children 12-24 months old. Conclusions: In Kenyan children presenting with diarrhea, C. difficile is more prevalent than rotavirus or Cryptosporidium, two leading causes of childhood diarrhea. These findings underscore the need to better understand the role of C. difficile in children with diarrhea, especially in areas with antibiotic overuse. Understanding C. difficile epidemiology and its relationship to co-infecting pathogens among African children with diarrhea will help in devising ways of reducing diarrhea-associated illness.

BackgroundDrug users act as reservoirs and transmission channels for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections to the general population worldwide. Periodic epidemiological studies to monitor the prevalence and genetic diversity of these infections to inform on interventions are limited.Objective of the studyThe objective of this study was to determine the predictors of HIV infection and genetic diversity of HBV and HCV among drug users in Kenya.Materials and methodsA cross-sectional study on previous drug use history among drug users was conducted in three Kenyan cities using a respondent-driven sampling method between January 2011 and September 2012. Blood samples were collected and analysed for the presence of HBV, HCV and HIV serological markers and to determine the genotypes of HBV and HCV.ResultsThe overall prevalence of HBV, HCV and HIV among drug users was 4.3%, 6.5% and 11.1%, respectively, with evidence of HBV/HIV, HCV/HIV and HBV/HCV/HIV co-infections. The HBV circulating genotypes were A1 (69%) and D6 (19%), whereas HCV genotypes were 1a (72%) and 4a (22%). Injection drug use was a significant predictor of HIV/HCV infections. Younger age (30 years; aOR (adjusted odds ratio) = 0.50, 95% CI (confidence interval): 0.33–0.76; p < 0.001) and early sexual debut (aOR = 0.54, 95% CI: 0.40–0.82; p < 0.05) were negatively associated with detection of any of the three infections. Injecting drug use was positively associated with HCV infection (aOR = 5.37, 95% CI: 2.61–11.06; p < 0.001).ConclusionThis high level of genetic diversity exhibited by HBV and HCV isolates requires urgent implementation of harm reduction strategies and continuous monitoring for effective management of the patients.

Background: Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea worldwide. As a result, the US Centers for Disease Control and Prevention have designated C. difficile as an urgent threat. Despite the global public health risk posed by CDI, little is known about its epidemiology on the African continent. This article describes the common occurrence of CDI from a cross-section of consecutively seen, randomly enrolled patients presenting with diarrhea at two major hospitals in Kenya. Methods: Patients presenting with diarrhea at two major hospitals in Kenya from May to July 2017 were enrolled. After signing the informed consent, stool samples, demographic data, medical history, prior antibiotic use, and HIV status were obtained from the patients. C. difficile was detected and validated by toxigenic culture and PCR. Results: The average age of the patients was 35.5 years (range 3–86 years); 59% were male and 41% were female. Out of 105 patient s tools tested, 98 (93.3%) were positive for C. difficile by culture. PCR analysis confirmed C. Difficile-specific genes, tcdA, tcdB, and tcdC, in the strains isolated from the stools. Further, 82.5% of the stools had C. difficile isolates bearing the frame-shift delection associated with hypervirulent strains. Remarkably, 91.9% of the stools that tested positive for C. difficile came from patients under 60 years old, with 64.3% being less than 40 years of age.The majorityof the patients (85%) reported over-the-counter antibiotic use in the last 30 days before the hospital visit. Conclusions: Together, the results revealed an unusually high incidence of C. difficile in the stools analyzed, especially among young adults who are thought to be less vulnerable. Comprehensive research is urgently needed to examine the epidemiology, risk factors, pathogenesis, comorbidities, clinical outcomes, antibiotic susceptibility, and genetic makeup of C. difficile strains circulating on the African continent.

BackgroundWith the persistent challenges towards controlling the HIV epidemic, there is an ongoing need for research into HIV vaccines and drugs. Sub-Saharan African countries - worst affected by the HIV pandemic - have participated in the conduct of clinical trials for HIV vaccines. In Kenya, the Kenya AIDS Vaccine Initiative (KAVI) at the University of Nairobi has conducted HIV vaccine clinical trials since 2001.MethodologyParticipants were recruited after an extensive informed consent process followed by screening to determine eligibility. Screening included an assessment of risk behavior, medical history and physical examination, and if clinically healthy, laboratory testing. In the absence of locally derived laboratory reference ranges, the ranges used in these trials were derived from populations in the West.Principal findingsTwo hundred eighty-one participants were screened between 2003 and 2006 for two clinical trials. Of these, 167 (59.4%) met the inclusion/exclusion criteria. Overall, laboratory abnormalities based on the non-indigenous laboratory references used were the most frequent reasons (61.4%) for ineligibility. Medical abnormalities contributed 30.7% of the total reasons for ineligibility. Based on the laboratory reference intervals now developed from East and Southern Africa, those ineligible due to laboratory abnormalities would have been 46.3%. Of the eligible participants, 18.6% declined enrolment.ConclusionsParticipant recruitment for HIV vaccine clinical trials is a rigorous and time-consuming exercise. Over 61% of the screening exclusions in clinically healthy people were due to laboratory abnormalities. It is essential that laboratory reference ranges generated from local populations for laboratory values be used in the conduct of clinical trials to avoid unnecessary exclusion of willing participants and to avoid over-reporting of adverse events for enrolled participants.Trial registrationProtocol IAVI VRC V001 [1]. ClinicalTrials.gov NCT00124007 Protocol IAVI 010 [2] (registration with ClincalTrials.gov is in progress) Protocols IAVI 002 and IAVI 004 are Phase 1 trials only mentioned in introductory paragraphs; details will not be reported. Registration was not required when they were conducted.