To understand the etiology of moderate-to-severe diarrhea among children in high mortality areas of sub-Saharan Africa and South Asia, we performed a comprehensive case/control study of children aged <5 years at 7 sites. Each site employed an identical case/control study design and each utilized a uniform comprehensive set of microbiological assays to identify the likely bacterial, viral and protozoal etiologies. The selected assays effected a balanced consideration of cost, robustness and performance, and all assays were performed at the study sites. Identification of bacterial pathogens employed streamlined conventional bacteriologic biochemical and serological algorithms. Diarrheagenic Escherichia coli were identified by application of a multiplex polymerase chain reaction assay for enterotoxigenic, enteroaggregative, and enteropathogenic E. coli. Rotavirus, adenovirus, Entamoeba histolytica, Giardia enterica, and Cryptosporidium species were detected by commercially available enzyme immunoassays on stool samples. Samples positive for adenovirus were further evaluated for adenovirus serotypes 40 and 41. We developed a novel multiplex assay to detect norovirus (types 1 and 2), astrovirus, and sapovirus. The portfolio of diagnostic assays used in the GEMS study can be broadly applied in developing countries seeking robust cost-effective methods for enteric pathogen detection.

BackgroundThe epidemiology of non-Typhi Salmonella (NTS) bacteremia in Africa will likely evolve as potential co-factors, such as HIV, malaria, and urbanization, also change.MethodsAs part of population-based surveillance among 55,000 persons in malaria-endemic, rural and malaria-nonendemic, urban Kenya from 2006–2009, blood cultures were obtained from patients presenting to referral clinics with fever ≥38.0°C or severe acute respiratory infection. Incidence rates were adjusted based on persons with compatible illnesses, but whose blood was not cultured.ResultsNTS accounted for 60/155 (39%) of blood culture isolates in the rural and 7/230 (3%) in the urban sites. The adjusted incidence in the rural site was 568/100,000 person-years, and the urban site was 51/100,000 person-years. In both sites, the incidence was highest in children <5 years old. The NTS-to-typhoid bacteremia ratio in the rural site was 4.6 and in the urban site was 0.05. S. Typhimurium represented >85% of blood NTS isolates in both sites, but only 21% (urban) and 64% (rural) of stool NTS isolates. Overall, 76% of S. Typhimurium blood isolates were multi-drug resistant, most of which had an identical profile in Pulse Field Gel Electrophoresis. In the rural site, the incidence of NTS bacteremia increased during the study period, concomitant with rising malaria prevalence (monthly correlation of malaria positive blood smears and NTS bacteremia cases, Spearman's correlation, p = 0.018 for children, p = 0.16 adults). In the rural site, 80% of adults with NTS bacteremia were HIV-infected. Six of 7 deaths within 90 days of NTS bacteremia had HIV/AIDS as the primary cause of death assigned on verbal autopsy.ConclusionsNTS caused the majority of bacteremias in rural Kenya, but typhoid predominated in urban Kenya, which most likely reflects differences in malaria endemicity. Control measures for malaria, as well as HIV, will likely decrease the burden of NTS bacteremia in Africa.

A virulent clone from Africa or southern Asia was likely introduced at a single time point.

A hospital-based surveillance study conducted by Ciara O'Reilly and colleagues describes the risk factors for death amongst children who have been hospitalized with diarrhea in rural Kenya.

A rotavirus vaccination program would reduce the substantial burden of rotavirus disease and the economic burden in Kenya.

We assessed the effect of daily cotrimoxazole, essential for HIV care, on development of antifolate-resistant Plasmodium falciparum, naso-pharyngeal Streptococcus pneumoniae (pneumococcus), and commensal Escherichia coli. HIV-positive subjects with CD4 cell count < 350 cells/muL (lower-CD4; N = 692) received cotrimoxazole; HIV-positive with CD4 cell count > or = 350 cells/muL (higher-CD4; N = 336) and HIV-negative subjects (N = 132) received multivitamins. Specimens were collected at baseline, 2 weeks, monthly, and at sick visits during 6 months of follow-up to compare changes in resistance, with higher-CD4 as referent. P. falciparum parasitemia incidence density was 16 and 156/100 person-years in lower-CD4 and higher-CD4, respectively (adjusted rate ratio [ARR] = 0.11; 95% confidence interval [CI] = 0.06-0.15; P < 0.001) and 97/100 person-years in HIV-negative subjects (ARR = 0.62; 95% CI = 0.44-0.86; P = 005). Incidence density of triple and quintuple dihydrofolate-reductase/dihydropteroate-synthetase mutations was 90% reduced in lower-CD4 compared with referent. Overall, cotrimoxazole non-susceptibility was high among isolated pneumococcus (92%) and E. coli (76%) and increased significantly in lower-CD4 subjects by Week 2 (P < 0.005). Daily cotrimoxazole prevented malaria and reduced incidence of antifolate-resistant P. falciparum but contributed to increased pneumococcus and commensal Escherichia coli resistance.

Continued surveillance of rotavirus AGE will provide timely data on the population-level impact of rotavirus vaccine following its likely introduction in 2014.

Background: Data on pneumococcal conjugate vaccine (PCV) indirect effects in low-income countries with high HIV burden are limited. We examined adult pneumococcal pneumonia incidence before and after 10-valent PCV introduction in Kenya in 2011. Methods: From 1/1/2008 to 12/31/2016, we conducted surveillance for acute respiratory infection (ARI) among ~12,000 adults (≥18 years) in western Kenya, where HIV prevalence ~17%. ARI cases (cough or difficulty breathing or chest pain, plus temperature ≥38.0◦C or oxygen saturation <90%) presenting to a clinic underwent blood culture and pneumococcal urine antigen testing (UAT). We calculated ARI incidence and adjusted for healthcare seeking using data from household visits. The proportion of ARI cases with pneumococcus detected among those with complete testing (blood culture and UAT) was multiplied by adjusted ARI incidence to estimate pneumococcal pneumonia incidence. Results: Pre-PCV (2008–2010), crude and adjusted ARI incidence were 3.14 and 5.30/100 person-years-observation (pyo), respectively. Among ARI cases, 39.0% (340/872) had both blood culture and UAT; 21.2% (72/340) had pneumococcus detected, yielding baseline pneumococcal pneumonia incidence of 1.12/100 pyo (95% confidence interval [CI] 1.0–1.3). In each post-PCV year (2012–2016), pneumococcal pneumonia incidence was significantly lower than baseline; with incidence rate ratios (IRR) of 0.53 (95%CI 0.31–0.61) in 2012 and 0.13 (95%CI 0.09–0.17) in 2016. Similar declines were observed in HIV-infected (IRR 0.13, 95%CI 0.08–0.22), and HIV-uninfected (IRR 0.10, 95%CI 0.05–0.20). Conclusions: Adult pneumococcal pneumonia declined in western Kenya following 10-valent PCV introduction, likely reflecting vaccine indirect effects. Evidence of herd protection is critical for guiding PCV policy decisions in resource-constrained areas.