Differing Burden and Epidemiology of Non-Typhi Salmonella Bacteremia in Rural and Urban Kenya, 2006–2009

2006-2009. PLoS ONE 7(2): e31237. doi:10.1371/journal.pone.0031237 Differing Burden and Epidemiology of Non-Typhi Salmonella Bacteremia in Rural and Urban Kenya, 2006- 2009 Collins Tabu 0 Robert F. Breiman 0 Benjamin Ochieng 0 Barrack Aura 0 Leonard Cosmas 0 Allan Audi 0 Beatrice Olack 0 Godfrey Bigogo 0 Juliette R. Ongus 0 Patricia Fields 0 Eric Mintz 0 Deron Burton 0 Joe 0 Oundo 0 Daniel R. Feikin 0 Dipshikha Chakravortty, Indian Institute of Science, India 0 1 Field Epidemiology and Laboratory Training Program, Nairobi, Kenya, 2 Ministry of Public Health and Sanitation, Nairobi, Kenya, 3 Kenya Medical Research Institute/ Centers for Disease Control and Prevention, Nairobi, Kenya, 4 Jomo Kenyatta University of Agriculture and Technology , Nairobi , Kenya , 5 International Emerging Infections Program, Global Disease Detection, Centers for Disease Control and Prevention, Nairobi, Kenya, 6 Division of Foodborne , Waterborne, and Environmental Diseases , Centers For Disease Control and Prevention , Atlanta, Georgia , United States of America Background: The epidemiology of non-Typhi Salmonella (NTS) bacteremia in Africa will likely evolve as potential co-factors, such as HIV, malaria, and urbanization, also change. Methods: As part of population-based surveillance among 55,000 persons in malaria-endemic, rural and malarianonendemic, urban Kenya from 2006-2009, blood cultures were obtained from patients presenting to referral clinics with fever $38.0uC or severe acute respiratory infection. Incidence rates were adjusted based on persons with compatible illnesses, but whose blood was not cultured. Results: NTS 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. Conclusions: NTS 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. - Funding: This work was supported by the Centers for Disease Control and Prevention. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Non-Typhi Salmonella (NTS) is a common cause of bacteremia among children and adults in Africa [112]. NTS bacteremia in Africa is highly associated with other diseases, particularly HIV and malnutrition, and possibly malaria [2,9,10,12]. As the epidemiology of these associated diseases evolves in Africa, the epidemiology and burden of NTS bacteremia may also change. Moreover, recent reports of a multi-drug resistant NTS clone, causing invasive disease in Africa suggests that the epidemiology of NTS bacteremia might also be in flux due to other selective pressures [13,14]. Lastly, as more Africans migrate to urban areas, living in crowded, squalid conditions, these new environments might also lead to a different epidemiology of NTS bacteremia. Updated epidemiologic data on NTS bacteremia can serve to guide future policy decisions on treatment and prevention. We evaluated three years of population-based surveillance on NTS bacteremia from an urban informal settlement in Nairobi and a rural area of western Kenya. Our surveillance highlights stark differences in invasive Salmonella epidemiology in urban and rural Africa and the close associations between NTS bacteremia and HIV and malaria. Study sites The Centers for Disease Control and Preventions (CDC) International Emerging Infections Program (IEIP) and the Kenya Medical Research Institute (KEMRI) have conducted populationbased morbidity surveillance since late 2005 in Asembo, in rural western Kenya and in Kibera, an informal settlement in Nairobi. The surveillance sites and design have been described previously [15,16]. In brief, the population from July, 2006 included approximately 25,000 and 30,000 persons in the rural and urban areas, respectively [15,16]. All participants must have resided permanently in the surveillance area for four calendar months [17]. In Asembo, malaria transmission is intense and occurs yearround [17]. In Kibera, the population lives in crowded conditions, with dirt paths between the dwellings and open sewers. Malaria is not endemic, but does occur particularly among those travelling to visit family in rural areas. Both sites have high adult prevalence of HIV at 1517% (KEMRI/CDC unpublished data). Surveillance methods Study participants receive free medical care for most acute conditions at a single referral health facility centrally-located in each site (Lwak Hospital in Asembo, Tabitha Clinic in Kibera). Patients are examined and diagnosed by clinical officers (similar to physicians assistants). Scannable paper questionnaires (TeleFormH, CardiffTM, California) or computerized databases (GFL Partners, Kenya) are completed on all sick visits, documenting symptoms, health-seeking, physical exam, diagnosis, treatment and outcome. Blood cultures are done on persons meeting one of three case definitions. 1. Severe acute respiratory illness (SARI), defined in persons $5 years old as cough or difficulty breathing and either temperature $38.0uC or oxygen saturation ,90%, and in children ,5 years old as those with clinical pneumonia as defined by WHOs Integrated Management of Childhood Illness [18]. 2. Acute febrile illness, defined as a temperature $38.0uC, without SARI or other obvious source (e.g. bloody diarrhea), irrespective of malaria blood smear result (only the first two Age category Rural Kenya child and first two adult patients who meet this criteria per day are enrolled). 3. All patients, regardless of age, admitted for conditions unrelated to injury or obstetrics, at Lwak Hospital. (Tabitha Clinic does not have inpatient capacity.) In addition, blood smears for malaria are done and read by KEMRI/CDC (...truncated)