Antimicrobial Resistance and Sickle Cell Protein Analysis in Invasive Non-Typhoidal Salmonella Isolated From Outpatient and Hospitalized Children Below 16 Years in Informal Settlements in Nairobi Kenya

Abstract Background: Invasive Non-typhoidal Salmonella (iNTS) disease continues to be a major public health problem, especially in sub Saharan Africa where incidence rates are 227 cases [range 152-341] per 100,000 population. Populations at risk of iNTS include adults with HIV infection, malnourished children, those with recent malaria or sickle-cell anaemia (SCA). Individuals with SCA are at an increased risk of invasive bacterial infections with the proportion of deaths from infection reported to be as high as 38% in the United States and 29% in Jamaica. In Kenya, iNTS disease is particularly a major challenge in poor informal settlements with infants and young children less than 5 years of age being the most affected; mortality rates can be 20-25% unless prompt treatment is administered. Methods Our study was conducted in 3 outpatient sites and 1 inpatient site, the outpatient sites were all located within Mukuru informal settlement, a densely populated slum, 15km East of Nairobi City. Blood and stool samples from children with fever alone and with fever and diarrhea were collected for processing for presence of iNTS using basic microbiology procedures. Dry blood spots were also taken and processed for sickle cell protein markers using High performance liquid chromatography (HPLC). Results A total of 22,246 blood and stool samples were collected from children < 16 years of age with fever/with or without diarrhea, for a period of 6 years and subjected to microbiological culture and detection of bacterial pathogens. Out of these 741 (3.3%) tested positive for Salmonella species. A total of 338/741(41%) NTS were isolated across all the sites; these consisted of 158/741(21%) Salmonella Enteritidis and 180/741 (24%) Salmonella Typhimurium. The most common resistance phenotype was ampicillin, cotrimoxazole and chloramphenicol (35.03%). We had 12/338 (3.6%) isolates (11 of them being Salmonella Typhimurium) that were ESBL producers conferring resistance to 3rd generation cephalosporins (Amp C β-lactamases) while only 0.3% were resistant to ciprofloxacin. A total of 118 (35.03%) isolates were MDR. Out of 2684 dry blood samples subjected to HPLC for investigation of sickle cell disease traits, 1820/2684 (67%) had normal hemoglobin (Hb AA/ Hb AF); (162/2684 (6%) tested positive for Sickle Cell Traits (Hb AS/Hb AFS); while 4/2684 (0.2%) tested positive for Sickle cell disease (Hb FS). Conclusion The high MDR resistance phenotype in iNTS isolates and emerging resistance to third generation cephalosporins is of great concern in management of iNTS in our settings. Sickle cell disease was not a major factor among children with iNTS disease and no significant association with iNTS was observed.