Correlates of multi-drug non-susceptibility in enteric bacteria isolated from Kenyan children with acute diarrhea.

BACKGROUND: Reduced antimicrobial susceptibility threatens treatment efficacy in sub-Saharan Africa, where data on the burden and correlates of antibiotic resistance among enteric pathogens are limited. METHODS: Fecal samples from children aged 6 mos-15 yrs presenting with acute diarrhea in western Kenya were cultured for bacterial pathogens. HIV-uninfected children with identified Shigella or Salmonella species or pathogenic Escherichia coli (EPEC, ETEC, EAEC or EIEC) were included in this cross-sectional sub-study. Non-susceptibility to ampicillin, ceftriaxone, ciprofloxacin, cotrimoxazole, and tetracycline was determined using MicroScan Walkaway40 Plus. Multivariable log-binomial regression was used to identify correlates of multi-drug non-susceptibility (MDNS, non-susceptibility to ≥ 3 of these antibiotics). RESULTS: Of 292 included children, median age was 22.5 mos. MDNS was identified in 62.5% of 318 isolates. Non-susceptibility to cotrimoxazole (92.8%), ampicillin (81.3%), and tetracycline (75.0%) was common. Young age (6-24 mos vs. 24-59 mos adjusted prevalence ratio [aPR] = 1.519 [95% confidence interval: 1.19, 1.91]), maternal HIV (aPR = 1.29 [1.01, 1.66]); and acute malnutrition (aPR = 1.28 [1.06, 1.55]) were associated with higher prevalence of MDNS, as were open defecation (aPR = 2.25 [1.13, 4.50]), household crowding (aPR = 1.29 [1.08, 1.53]) and infrequent caregiver hand-washing (aPR = 1.50 [1.15, 1.95]). CONCLUSIONS: Young age, HIV exposure, acute malnutrition and poor sanitation may increase risk of antibiotic non-susceptible enteric pathogen infections among children in Kenya.

Low Bacteremia Prevalence Among Febrile Children in Areas of Differing Malaria Transmission in Rural Kenya: A Cross-Sectional Study.

BACKGROUND: With malaria declining, other causes of fever may account for a substantial portion of severe childhood illness in sub-Saharan Africa. We determined prevalence, etiologies, and correlates of bacteremia among children in Western Kenya. METHODS: In a cross-sectional study, febrile children aged 6 months to 15 years presenting to Kisii (low malaria endemicity) and Homabay (high malaria endemicity) Hospitals were enrolled and screened for malaria, human immunodeficiency virus (HIV) infection and bacteremia. Correlates of bacteremia were evaluated using logistic regression. RESULTS: Among 1476 children enrolled, 48 (3.3%) had bacteremia (23 of 734, 3.1% in Kisii and 25 of 734, 3.4% in Homabay). Salmonella spp (19 typhi and 21 nontyphoidal salmonella) accounted for 83% (40 of 48) of isolates. The distribution of Salmonella spp was similar between sites. Bacteremia was associated with incomplete vaccination (adjusted odds ratio [aOR] = 2.1; 95% confidence interval [CI], 1.1-4.1), before treatment with antimalarials (aOR = 2.7; 95% CI, 1.4-4.1), having sought care elsewhere (aOR = 2.2; 95% CI, 1.2-4.0) and lower education of caregiver (aOR = 2.5; 95% CI, 1.1-4.8). Nontyphoidal salmonella bacteremia was associated with HIV (aOR = 6.8; 95% CI, 1.1-35.1) and anemia (hemoglobin <8 g/dL) (aOR = 5.2; 95% CI, 1.4-18.9). CONCLUSIONS: Bacteremia was relatively uncommon, but children with HIV, anemia, incomplete vaccination, and/or persistent fever despite malaria treatment may have higher risk and may benefit from targeted bacterial culture and/or empiric antibiotic therapy.

Frequency and correlates of malaria over-treatment in areas of differing malaria transmission: a cross-sectional study in rural Western Kenya.

BACKGROUND: In 2010, the World Health Organization shifted its malaria guidelines from recommending the empiric treatment of all febrile children to treating only those with laboratory-confirmed malaria. This study evaluated the frequency and predictors of malaria over-treatment among febrile malaria-negative children in Kenya. METHODS: Between 2012 and 2013, 1,362 children presenting consecutively with temperature ≥37.5°C to Kisii and Homa Bay hospitals were enrolled in a cross-sectional study evaluating causes of fever. Children were screened for malaria using smear microscopy and rapid diagnostic tests and managed according to standard of care at the hospitals. The frequency of anti-malarial prescriptions among children with laboratory-confirmed malaria negative children (malaria over-treatment) was determined; and clinical and demographic correlates of overtreatment evaluated using logistic regression. Because of differences in malaria endemicity, analyses were stratified and compared by site. RESULTS: Among 1,362 children enrolled, 46 (7%) of 685 children in Kisii, and 310 (45.8%) of 677 in Homa Bay had laboratory-confirmed malaria; p < 0.001. Among malaria-negative children; 210 (57.2%) in Homa Bay and 45 (7.0%) in Kisii received anti-malarials; p < 0.001. Predictors of over-treatment in Homa Bay included ≥ one integrated management of childhood illness (IMCI) danger sign (aOR = 8.47; 95% CI: 4.81-14.89), fever lasting ≥ seven days (aOR = 4.94; 95% CI: 1.90-12.86), and fever ≥39°C (aOR = 3.07; 95% CI: 1.58-5.96). In Kisii, only fever ≥39°C predicted over-treatment (aOR = 2.13; 95% CI: 1.02-4.45). CONCLUSIONS: Malaria over-treatment was common, particularly in Homa Bay, where the prevalence of malaria was extremely high. Severe illness and high or prolonged fever were associated with overtreatment. Overtreatment may result in failure to treat other serious causes of fever, drug resistance, and unnecessarily treatment costs.

Impact of helminth diagnostic test performance on estimation of risk factors and outcomes in HIV-positive adults.

BACKGROUND: Traditional methods using microscopy for the detection of helminth infections have limited sensitivity. Polymerase chain reaction (PCR) assays enhance detection of helminths, particularly low burden infections. However, differences in test performance may modify the ability to detect associations between helminth infection, risk factors, and sequelae. We compared these associations using microscopy and PCR. METHODS: This cross-sectional study was nested within a randomized clinical trial conducted at 3 sites in Kenya. We performed microscopy and real-time multiplex PCR for the stool detection and quantification of Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale, Strongyloides stercoralis, and Schistosoma species. We utilized regression to evaluate associations between potential risk factors or outcomes and infection as detected by either method. RESULTS: Of 153 HIV-positive adults surveyed, 55(36.0%) and 20(13.1%) were positive for one or more helminth species by PCR and microscopy, respectively (p<0.001). PCR-detected infections were associated with farming (Prevalence Ratio 1.57, 95% CI: 1.02, 2.40), communal water source (PR 3.80, 95% CI: 1.01, 14.27), and no primary education (PR 1.54, 95% CI: 1.14, 2.33), whereas microscopy-detected infections were not associated with any risk factors under investigation. Microscopy-detected infections were associated with significantly lower hematocrit and hemoglobin (means of -3.56% and -0.77 g/dl) and a 48% higher risk of anemia (PR 1.48, 95% CI: 1.17, 1.88) compared to uninfected. Such associations were absent for PCR-detected infections unless infection intensity was considered, Infections diagnosed with either method were associated with increased risk of eosinophilia (PCR PR 2.42, 95% CI: 1.02, 5.76; microscopy PR 2.92, 95% CI: 1.29, 6.60). CONCLUSION: Newer diagnostic methods, including PCR, improve the detection of helminth infections. This heightened sensitivity may improve the identification of risk factors for infection while reducing ability to discriminate infections associated with adverse clinical outcomes. Quantitative assays can be used to differentiate infection loads and discriminate infections associated with sequelae.