Determinants of diarrheal disease in children undergoing complementary feeding in a low-income urban setting in Kenya.

OBJECTIVES: This study aimed to identify and characterise the determinants influencing the occurrence of diarrheal diseases in children aged 6-24 months undergoing complementary feeding within a low-income urban community in Kenya. METHODS: This study followed a cross-sectional design and recruited caregivers of children aged 6-24 months from 302 households. The dependent variable was the 2-week diarrhoea prevalence among children, with independent variables including sociodemographic characteristics, child immunisation and feeding status, and water and sanitation facilities. Data analysis was performed using SPSS. Descriptive statistics and logistic regression analyses were used to assess associations between independent variables and the occurrence of diarrheal diseases. RESULTS: The majority of caregivers were female (n = 282, 93.4%), aged 25-34 years (n = 156, 51.7%), had attained secondary school education (n = 154, 51%), were unemployed (n = 162, 53.6%), and earned Ksh 10,000 (USD 100) or less. 296 (98%) indexed children were fully vaccinated against rotavirus. Most households used improved drinking water sources (n = 272, 90.1%). Most caregivers did not regularly wash their hands with soap and water (n = 225, 74.5%). The 2-week diarrhoea prevalence among children was 34.1% (103/302), with 69.9% (72/103) of these cases seeking care at a healthcare facility. Logistic regression analysis revealed that children of caregivers earning Ksh 20,000 and below (aOR = 2.9[1.3-6.5], p = 0.01), and those from households using unimproved sanitation facilities (aOR = 1.9 [CI 1-3.4], p = 0.042), had significantly higher odds of having diarrhoea. CONCLUSION: The study found a high prevalence of diarrhoea in Kenyan children aged 6-24 months, with caregiver income and household sanitation facilities significantly impacting the occurrence of the disease. The study suggests integrated approaches, including education, income generation, hygiene, and improved nutrition, to address the burden of diarrheal disease.

Community education training to optimize the use of artemisinin-based combination therapy in Kamuli District, Uganda.

BACKGROUND: Community health education improves members health-seeking and utilization behaviours. To enhance the community knowledge and optimize the use of Artemisinin-based combination therapy (ACT), we carried out a community training in Kamuli District, Uganda. METHODS: The Analysis, Design, Development, Implementation and Evaluation (ADDIE) model was adopted. A total of 3420 community members were trained, 384 sampled to participate in pre-post-test assessment, with 76 healthcare workers (HCW). Community members were sampled by simple random sampling while the HCW were purposively selected. Community trainings occurred for two days at each of 42 public health facilities and one day at 27 parishes. A paired sample t-test and effect size was computed to establish effect with statistical significance tested at p < 0.05. RESULTS: Overall, a total of 3496 participants, majority 2705 (77.4%) females were trained. A total of 3420 community members, majority 2659 (77.7%) females trained, and 76 HCW, majority 46 (60.5%) females trained. The median age of community participants was 32 years, and interquartile range (IQR) = 17 years. The median age of HCW was 32 years, and IQR = 8 years. The training had a positive and significant effect on the community members knowledge: malaria transmission (T-test = 9.359; p < 0.0001) causes of malaria (T-test = 6.738; p < 0.0001), malaria symptoms (T-test = 5.403; p < 0.0001), dangerous malaria species (T-test = 12.088; p < 0.0001), Plasmodium vivax malaria cycle and occurrence every 48 h (T-test = 7.470; p < 0.0001), assessing whether a patient with malaria may suffer from jaundice (T-test = 7.228; p < 0.0001), organs affected by Plasmodium falciparum (T-test = 12.214; p < 0.0001), malaria diagnosis (T-test = 9.765; p < 0.0001), Plasmodium associated with malaria relapse (T-test = 10.250; p < 0.0001), and malaria prevention and control (T-test = 9.278; p < 0.0001). The intervention also had a significant and positive effect on HCW knowledge on all domains except on malaria transmission (T-test = 1.217; p = 0.228) where it didn't have any statistically significant increase on their knowledge. CONCLUSION: The education intervention improved the knowledge of participants significantly. There is need to adopt and scale-up the current intervention at all levels of care to enhance proper use of medicines.

Factors influencing patients' adherence to malaria artemisinin-based combination therapy in Kamuli District, Uganda.

BACKGROUND: Patients' adherence to artemisinin-based combination therapy (ACT) is a malaria control strategy. Studies report varied experiences regarding patients' adherence to ACT. The study aimed at determining factors influencing patients' adherence to ACT for malaria in Kamuli, Uganda. METHODS: In a longitudinal study, 1266 participants at 8 public health facilities were enrolled. Equal numbers (422) were assigned to the three arms (no follow-up, day 2 and day 4). To establish the mean difference between groups, Student t-test was used and a chi-square test was used for proportionality. A multivariate logistic regression analysis was used to establish the influence of predictor variables on the dependent variable. Statistical significance was established at p < 0.05. RESULTS: A total of 844 patients were analysed. The median age was 20 years, majority (64.3%) were females. Overall patients' adherence was 588/844 (69.7%). At bivariate level, age (t-test = 2.258, p = 0.024), household head (χ2 = 14.484, p = 0.002), employment status (χ2 = 35.886, p < 0.0001), patients' preference of ACT to other anti-malarials (χ2 = 15.981, p < 0.0001), giving a patient/caregiver instructions on how to take the medication (χ2 = 7.134, p = 0.011), being satisfied with getting ACT at facility (χ2 = 48.261, p < 0.0001), patient/caregiver knowing the drug prescribed (χ2 = 5.483, p = 0.019), patient history of saving ACT medicines (χ2 = 39.242, p < 0.0001), and patient ever shared ACT medicines (χ2 = 30.893, p < 0.0001) were all associated with patients' adherence to ACT. Multivariate analysis demonstrated that adhering to ACT is 3.063 times higher for someone satisfied with getting ACT at the facility (OR = 3.063; p < 0.0001), 4.088 times for someone with history of saving ACT medicines (OR = 4.088; p < 0.0001), 2.134 times for someone who shared ACT (OR = 2.134; p = 0.03), and 2.817 times for someone with a household head (OR = 2.817; p = 0.008). CONCLUSION: Patients' adherence to ACT is generally good in the studied population. However, patients' tendencies to save ACT for future use and sharing among family members is a threat, amidst the benefits associated with adherence. There is a need to educate all about adherence to medicines as prescribed, and tighten government medicine supply chain to avoid stock-outs.

The role of vitamin D status on treatment outcome among HIV- infected children receiving care in Kisumu County, Kenya.

Background: Kenya has a paediatric HIV burden of nearly 140,000 children, of which only 48% of those on antiretroviral therapy (ART) have achieved the desired viral suppression possibly due to vitamin D deficiency. We explored the influence of vitamin D levels on treatment outcome. Method: We performed a cross-sectional study of 196 participants aged 3 - 14 years; among them 98 HIV infected who received treatment between 2019 - 2020 in Jaramogi Oginga Odinga Teaching and Referral Hospital, Kenya. The exposure was vitamin D levels, including deficient (<20 ng/ml), insufficient (≥20 - <30 ng/ml), and sufficient (30 - 50ng/ml). The outcome was optimal immune recovery (CD4 ≥ 500 cells/mm3) and optimal viral suppression (viral load ≤ 200 copies/ml). We compared difference in means for each vitamin D category between HIV infected and uninfected using independent t-test, multiple comparisons of vitamin D levels among age categories using ANOVA and post hoc test and Pearson correlation to correlate vitamin D levels, CD4 and viral load of HIV infected children. Results: Compared with HIV uninfected, HIV infected recorded mean age ± standard deviation of10.65±2.17 years with 39(39.8%) males vs. 6.68±2.81 years with 52(53.1%) males p<0.001; and the difference in vitamin D mean levels was statistically significant [28.21 ± 6.39 infected vs.30.88 ± 6.62 uninfected] t = 2.94, df =194, p = 0.004, 95%CI (0.90 - 4.59). Among age categories, mean vitamin D varied significantly F (2,193) = 10.68, p =0.001; with higher levels observed between 1-4 years category {mean difference 4.64ng/ml, p = 0.02, [95%CI 1.49 - 7.78]} and 5-9 years category {mean difference 4.33ng/ml, p = 0.001, [95%CI 1.89 - 6.38]} as compared to 10 - 14 years respectively.Additionally, children with optimal immune recovery recorded higher proportion of vitamin D deficiency and insufficiency (12.24% and 42.86%) as compared with sub optimally recovered 1.02% and 4.08%); while children with optimal viral suppression recorded higher proportion of vitamin D deficiency and insufficiency (8.16% and 30.61%) as compared with sub optimally suppressed (5.1% and 16.3%). Conclusion: Infections with HIV suppresses levels of vitamin D, but this has no influence on CD4 counts and viral load status in children receiving ART.

Predictors of mortality and survival probability distribution among patients on tuberculosis treatment in Vihiga County, Kenya.

Background: Tuberculosis (TB) related mortality remains a serious impediment in ending TB epidemic. Objective: To estimate survival probability and identify predictors, causes and conditions contributing to mortality among TB patients in Vihiga County. Methods: A cohort of 291 patients from 20 purposively selected health facilities were prospectively considered. Data was obtained by validated questionnaires through face-to-face interviews. Survival probabilities were estimated using Kaplan-Meier method while Cox proportional hazard model identified predictors of TB mortality through calculation of hazard ratios at 95% confidence intervals. Mortality audit data was qualitatively categorized to elicit causes and conditions contributing to mortality. Results: 209 (72%) were male, median age was 40 (IQR=32-53) years while TB/HIV coinfection rate was 35%. Overall, 45 (15%) patients died, majority (78% (log rank<0.001)) during intensive phase. The overall mortality rate was 32.2 (95% CI 23.5 - 43.1) deaths per 1000 person months and six months' survival probability was 0.838 (95% CI, 0.796-0.883). Mortality was higher (27%) among HIV positive than HIV negative (9%) TB patients. Independent predictors of mortality included; comorbidities (HR = 2.72, 95% CI,1.36-5.44, p< 0.005), severe illness (HR=5.06, 95% CI,1.59-16.1, p=0.006), HIV infection (HR=2.56, 95% CI,1.28-5.12, p=0.008) and smoking (HR=2.79, 95% CI,1.01-7.75, p=0.049). Independent predictors of mortality among HIV negative patients included; comorbidities (HR = 4.25, 95% CI; 1.15-15.7, p = 0.03) and being clinically diagnosed (HR = 4.8, 95% CI; 1.43-16, P = 0.01) while among HIV positive; they included smoking (HR = 4.05, 95% CI;1.03-16.0, P = 0.04), severe illness (HR = 5.84, 95% CI; 1.08-31.6, P = 0.04), severe malnutrition (HR = 4.56, 95% CI; 1.33-15.6, P = 0.01) and comorbidities (HR = 3.04, 95% CI; 1.03-8.97, p = 0.04). More than a half (52%) of mortality among HIV positive were ascribed to advanced HIV diseases while majority of (72%) of HIV negative patients died to TB related lung disease. Conditions contributing to mortality were largely patient and health system related. Conclusion: Risk of TB mortality is high and is attributable to comorbidities, severe illness, HIV and smoking. Causes and conditions contributing to TB mortality are multifaceted but modifiable. Improving TB/HIV care could reduce mortality in this setting.

Nasal Carriage of Methicillin-Resistant Staphylococcus Sciuri Group by Residents of an Urban Informal Settlement in Kenya.

Background: The Staphylococcus sciuri group constitutes animal-associated bacteria but can comprise up to 4% of coagulase-negative staphylococci isolated from human clinical samples. They are reservoirs of resistance genes that are transferable to Staphylococcus aureus but their distribution in communities in sub-Saharan Africa is unknown despite the clinical importance of methicillin-resistant S. aureus. Objectives: We characterised methicillin-resistant S. sciuri group isolates from nasal swabs of presumably healthy people living in an informal settlement in Nairobi to identify their resistance patterns, and carriage of two methicillin resistance genes. Method: Presumptive methicillin-resistant S. sciuri group were isolated from HardyCHROM™ methicillin-resistant S. aureus media. Isolate identification and antibiotic susceptibility testing were done using the VITEK®2 Compact. DNA was extracted using the ISOLATE II genomic kit and polymerase chain reaction used to detect mecA and mecC genes. Results: Of 37 presumptive isolates, 43% (16/37) were methicillin-resistant including - S. sciuri (50%; 8/16), S. lentus (31%; 5/16) and S. vitulinus (19%; 3/16). All isolates were susceptible to ciprofloxacin, gentamycin, levofloxacin, moxifloxacin, nitrofurantoin and tigecycline. Resistance was observed to clindamycin (63%), tetracycline (56%), erythromycin (56%), sulfamethoxazole/trimethoprim (25%), daptomycin (19%), rifampicin (13%), doxycycline, linezolid, and vancomycin (each 6%). Most isolates (88%; 14/16) were resistant to at least 2 antibiotic combinations, including methicillin. The mecA and mecC genes were identified in 75% and 50% of isolates, respectively. Conclusion: Colonizing S. sciuri group bacteria can carry resistance to methicillin and other therapeutic antibiotics. This highlights their potential to facilitate antimicrobial resistance transmission in community and hospital settings. Surveillance for emerging multidrug resistant strains should be considered in high transmission settings where human-animal interactions are prevalent. Our study scope precluded identifying other molecular determinants for all the observed resistance phenotypes. Larger studies that address the prevalence and risk factors for colonization with S. sciuri group and adopt a one health approach can complement the surveillance efforts.

Resistance of Anopheles gambiae sensu lato to Pirimiphos-methyl Insecticide in Kakamega County, Highlands of Western Kenya.

Background: Insecticide treated bed nets and Indoor residual spraying remains the principal interventional malaria control strategies. To achieve malaria disease eradication, vector control programmes that monitor insecticide resistance profiles are necessary. Objective: The study evaluated pirimiphos-methyl susceptibility of Anopheles gambiae sensu lato in Kakamega County, western Kenya. Methods: Adult Anopheles gambiae sensu lato mosquitoes were assayed using World Health Organization tube bioassay against 0.25% pirimiphos-methyl. Susceptible and non-susceptible populations were characterized to species-level using Polymerase Chain Reaction. Susceptible and resistant mosquitoes were further subjected to G119S Acetylcholisterase (ace 1R) mutation detection. Results: Anopheles arabiensis was the predominant species in all study population Mumias east (62%), Malava (68%), Ikolomani (77%) and Lurambi (82%). Results showed phenotypic susceptibility to pirimiphos-methyl. Mortality was low in Mumias east (80.6%) and high in Lurambi (89.0%). G119S mutations ranged from 3.0% to 8.9% in Anopheles arabiensis whereas G119S mutations were relatively low ranging from 0.0% to 3.1% in Anopheles gambiae s.s populations. Study populations tested were consistent with Hardy-Weinberg equilibrium (P>0.05). Conclusion: We observed pirimiphos-methyl resistance in Anopheles arabiensis and Anopheles gambiae s.s. study populations. Results showed G119S mutation in resistance population. Resistance monitoring and management are urgently required.

Determinants of tuberculosis treatment interruption among patients in Vihiga County, Kenya.

BACKGROUND: Despite robust Tuberculosis (TB) program with effective chemotherapy and high coverage, treatment interruption remains a serious problem. Interrupting TB treatment means that patients remain infectious for longer time and are at risk of developing drug resistance and death. This study was conducted to identify and describe predictors of TB treatment interruption. METHODS: A cohort of 291 notified TB patients from 20 selected health facilities in Vihiga County were enrolled in to the study and followed up until the end of treatment. Patient characteristics that potentially predict treatment interruption were recorded during treatment initiation using structured questionnaires. Patients who interrupted treatment were traced and reasons for stoppage of treatment recorded. Kaplan Meier method was used to estimate probabilities of treatment interruption by patient characteristics and determine time intervals. The Log rank test for the equality of survival distributions analyzed significance of survival differences among categorical variables. For multivariable analysis, Cox proportional hazard model, was fitted to identify predictors of TB treatment interruption through calculation of hazard ratios with 95% Confidence Intervals (CIs). For variable analysis, statistical significance was set at P ≤ 0.05. Reasons for treatment interruption were categorized according to most recurrent behavioral or experiential characteristics. RESULTS: Participants' median age was 40 years (IQR = 32-53) and 72% were male. Of the 291 patients, 11% (n = 32) interrupted treatment. Incidences of treatment interruption significantly occurred during intensive phase of treatment. Independent predictors of treatment interruption included alcohol consumption (HR = 9.2, 95% CI; 2.6-32.5, p < 0.001), being female (HR = 5.01, 95% CI; 1.68-15.0, p = 0.004), having primary or lower education level (HR = 3.09, 95% CI; 1.13-8.49, p < 0.029) and having a treatment supporter (HR = 0.33, 95% CI; 0.14-0.76, p = 0.009). Reasons for interrupting treatment were categorized as: alcoholism, feeling better after treatment initiation, associated TB stigma, long distance to health facility, lack of food, perception of not having TB and pill burden. CONCLUSION: TB treatment interruption was high and largely associated with patients' socio-demographic and behavioral characteristics. These multidimensional factors suggest the need for interventions that not only target individual patients but also environment in which they live and receive healthcare services.

Mapping geographic clusters of new HIV diagnoses to inform granular-level interventions for HIV epidemic control in western Kenya.

BACKGROUND: As countries make progress towards HIV epidemic control, there is increasing need to identify finer geographic areas to target HIV interventions. We mapped geographic clusters of new HIV diagnoses, and described factors associated with HIV-positive diagnosis, in order to inform targeting of HIV interventions to finer geographic areas and sub-populations. METHODS: We analyzed data for clients aged > 15 years who received home-based HIV testing as part of a routine public health program between May 2016 and July 2017 in Siaya County, western Kenya. Geospatial analysis using Kulldorff's spatial scan statistic was used to detect geographic clusters (radius < 5 kilometers) of new HIV diagnoses. Factors associated with new HIV diagnosis were assessed in a spatially-integrated Bayesian hierarchical model. RESULTS: Of 268,153 clients with HIV test results, 2906 (1.1%) were diagnosed HIV-positive. We found spatial variation in the distribution of new HIV diagnoses, and identified nine clusters in which the number of new HIV diagnoses was significantly (1.56 to 2.64 times) higher than expected. Sub-populations with significantly higher HIV-positive yield identified in the multivariable spatially-integrated Bayesian model included: clients aged 20-24 years [adjusted relative risk (aRR) 3.45, 95% Bayesian Credible Intervals (CI) 2.85-4.20], 25-35 years (aRR 4.76, 95% CI 3.92-5.81) and > 35 years (aRR 2.44, 95% CI 1.99-3.00); those in polygamous marriage (aRR 1.84, 95% CI 1.55-2.16), or separated/divorced (aRR 3.36, 95% CI 2.72-4.08); and clients who reported having never been tested for HIV (aRR 2.35, 95% CI 2.02-2.72), or having been tested > 12 months ago (aRR 1.53, 95% CI 1.41-1.66). CONCLUSION: Our study used routine public health program data to identify granular geographic clusters of higher new HIV diagnoses, and sub-populations with higher HIV-positive yield in the setting of a generalized HIV epidemic. In order to target HIV testing and prevention interventions to finer granular geographic areas for maximal epidemiologic impact, integrating geospatial analysis into routine public health programs can be useful.

Development and Validation of a Sociodemographic and Behavioral Characteristics-Based Risk-Score Algorithm for Targeting HIV Testing Among Adults in Kenya.

To inform targeted HIV testing, we developed and externally validated a risk-score algorithm that incorporated behavioral characteristics. Outpatient data from five health facilities in western Kenya, comprising 19,458 adults ≥ 15 years tested for HIV from September 2017 to May 2018, were included in univariable and multivariable analyses used for algorithm development. Data for 11,330 adults attending one high-volume facility were used for validation. Using the final algorithm, patients were grouped into four risk-score categories: ≤ 9, 10-15, 16-29 and ≥ 30, with increasing HIV prevalence of 0.6% [95% confidence interval (CI) 0.46-0.75], 1.35% (95% CI 0.85-1.84), 2.65% (95% CI 1.8-3.51), and 15.15% (95% CI 9.03-21.27), respectively. The algorithm's discrimination performance was modest, with an area under the receiver-operating-curve of 0.69 (95% CI 0.53-0.84). In settings where universal testing is not feasible, a risk-score algorithm can identify sub-populations with higher HIV-risk to be prioritized for HIV testing.

Novel biomarkers with promising benefits for diagnosis of cervical neoplasia: a systematic review.

BACKGROUND: Cervical cancer screening is slowly transitioning from Pappanicolaou cytologic screening to primary Visual Inspection with Acetic Acid (VIA) or HPV testing as an effort to enhance early detection and treatment. However, an effective triage tests needed to decide who among the VIA or HPV positive women should receive further diagnostic evaluation to avoid unnecessary colposcopy referrals is still lacking. Evidence from experimental studies have shown potential usefulness of Squamous Cell Carcinoma Antigen (SCC Ag), Macrophage Colony Stimulating Factor (M-CSF), Vascular Endothelial Growth Factor (VEGF), MicroRNA, p16INKa / ki-67, HPV E6/E7/mRNA, and DNA methylation biomarkers in detecting premalignant cervical neoplasia. Given the variation in performance, and scanty review studies in this field, this systematic review described the diagnostic performance of some selected assays to detect high-grade cervical intraepithelial neoplasia (CIN2+) with histology as gold standard. METHODS: We systematically searched articles published in English between 2012 and 2020 using key words from PubMed/Medline and SCOPUS with two reviewers assessing study eligibility, and risk of bias. We performed a descriptive presentation of the performance of each of the selected assays for the detection of CIN2 + . RESULTS: Out of 298 citations retrieved, 58 articles were included. Participants with cervical histology yielded CIN2+ proportion range of 13.7-88.4%. The diagnostic performance of the assays to detect CIN2+ was; 1) SCC-Ag: range sensitivity of 78.6-81.2%, specificity 74-100%. 2) M-CSF: sensitivity of 68-87.7%, specificity 64.7-94% 3) VEGF: sensitivity of 56-83.5%, specificity 74.6-96%. 4) MicroRNA: sensitivity of 52.9-67.3%, specificity 76.4-94.4%. 5) p16INKa / ki-67: sensitivity of 50-100%, specificity 39-90.4%. 6) HPV E6/E7/mRNA: sensitivity of 65-100%, specificity 42.7-90.2%, and 7) DNA methylation: sensitivity of 59.7-92.9%, specificity 67-98%. CONCLUSION: Overall, the reported test performance and the receiving operating characteristics curves implies that implementation of p16ink4a/ki-67 assay as a triage for HPV positive women to be used at one visit with subsequent cryotherapy treatment is feasible. For the rest of assays, more robust clinical translation studies with larger consecutive cohorts of women participants is recommended.

Epidemiological patterns and antimicrobial resistance of bacterial diarrhea among children in Nairobi City, Kenya.

AIM: Determine the prevalence of enteric bacterial pathogens and their antimicrobial resistance among diarrheic children in Nairobi City, Kenya. BACKGROUND: Regardless of enteric bacterial pathogens being a major cause of gastroenteritis in children, their occurrence and antimicrobial resistance patterns reveals regional spatial and temporal variation. METHODS: In a cross-sectional study, a total of 374 children below five years presenting with diarrhea at Mbagathi County Hospital were recruited. Stool microbiology test was used to detect enteric bacterial infection. Antimicrobial resistance was determined using the disk diffusion method. RESULTS: Diarrheagenic E. coli (36.4%) was the leading species followed by Shigella (3.2%), Salmonella (2.4%), Campylobacter (1.6%), Yersinia (1.3%) and Aeromonas (1.1%) species. Escherichia coli pathotyping revealed that 20.9%, 4.0%, 10.2% and 0.5% of the study participants were infected with enteroaggregative E. coli (EAEC), enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC) and enteroinvasive E. coli (EIEC) pure isolates while the prevalence of mixed pathotype infections was 0.3% for EAEC/EPEC/ETEC and 0.5% for EAEC/ETEC. Shigella sero-grouping revealed that 0.5%, 0.3%, 1.9%, and 0.5% were infected with Shigella boydii, Shigella dysentriae, Shigella flexneri and Shigella sonnei pure isolates. Shigella species and E. coli co-infection was detected in 2.4% of the children, specifically, 1.1% for EAEC/Shigella boydii, 0.5% for EAEC/Shigella dysentriae and 0.3% in each case of EAEC/Shigella sonnei, EPEC/Shigella flexneri and ETEC/Shigella flexneri co-infections. Most of the isolates were resistant to commonly prescribed antibiotics. CONCLUSION: There was a high prevalence of enteric bacterial pathogens and co-infection alters epidemiological dynamics of bacterial diarrhea in children. Continuous antibiotic resistance surveillance is justified because the pathogens were highly resistant to commonly prescribed antimicrobials.

Influence of blood group, Glucose-6-phosphate dehydrogenase and Haemoglobin genotype on Falciparum malaria in children in Vihiga highland of Western Kenya.

BACKGROUND: Genetic diversity of ABO blood, glucose-6-phosphate dehydrogenase (G6PD) deficiency and haemoglobin type and their ability to protect against malaria vary geographically, ethnically and racially. No study has been carried out in populations resident in malaria regions in western Kenya. METHOD: A total of 574 malaria cases (severe malaria anaemia, SMA = 137 and non-SMA = 437) seeking treatment at Vihiga County and Referral Hospital in western Kenya, were enrolled and screened for ABO blood group, G6PD deficiency and haemoglobin genotyped in a hospital-based cross-sectional study. RESULT: When compared to blood group O, blood groups A, AB and B were not associated with SMA (P = 0.380, P = 0.183 and P = 0.464, respectively). Further regression analysis revealed that the carriage of the intermediate status of G6PD was associated with risk to SMA (OR = 1.52, 95%CI = 1.029-2.266, P = 0.035). There was, however, no association between AS and SS with severe malaria anaemia. Co-occurrence of both haemoglobin type and G6PD i.e. the AA/intermediate was associated with risk to SMA (OR = 1.536, 95%CI = 1.007-2.343, P = 0.046) while the carriage of the AS/normal G6PD was associated with protection against SMA (OR = 0.337, 95%CI = 0.156-0.915, P = 0.031). CONCLUSION: Results demonstrate that blood group genotypes do not have influence on malaria disease outcome in this region. Children in Vihiga with blood group O have some protection against malaria. However, the intermediate status of G6PD is associated with risk of SMA. Further, co-inheritance of sickle cell and G6PD status are important predictors of malaria disease outcome. This implies combinatorial gene function in influencing disease outcome.

Evaluation of morbidity in Schistosoma mansoni-positive primary and secondary school children after four years of mass drug administration of praziquantel in western Kenya.

BACKGROUND: World Health Organization guidelines recommend preventive chemotherapy with praziquantel to control morbidity due to schistosomiasis. The primary aim of this cross-sectional study was to determine if 4 years of annual mass drug administration (MDA) in primary and secondary schools lowered potential markers of morbidity in infected children 1 year after the final MDA compared to infected children prior to initial MDA intervention. METHODS: Between 2012 and 2016 all students in two primary and three secondary schools within three kilometers of Lake Victoria in western Kenya received annual mass praziquantel administration. To evaluate potential changes in morbidity we measured height, weight, mid-upper arm circumference, hemoglobin levels, abdominal ultrasound, and quality of life in children in these schools. This study compared two cross-sectional samples of Schistosoma mansoni egg-positive children: one at baseline and one at year five, 1 year after the fourth annual MDA. Data were analyzed for all ages (6-18 years old) and stratified by primary (6-12 years old) and secondary (12-18 years old) school groups. RESULTS: The prevalence of multiple potential morbidity markers did not differ significantly between the egg-positive participants at baseline and those at 5 years by Mann Whitney nonparametric analysis and Fisher's exact test for continuous and categorical data, respectively. There was a small but significantly higher score in school-related quality of life assessment by year five compared to baseline by Mann Whitney analysis (P = 0.048) in 13-18 year olds where malaria-negative. However, anemia was not positively impacted by four annual rounds of MDA, but registered a significant negative outcome. CONCLUSIONS: We did not detect differences in morbidity markers measured in a population of those infected or re-infected after multiple MDA. This could have been due to their relative insensitivity or a failure of MDA to prevent morbidity among those who remain infected. High malaria transmission in this area and/or a lack of suitable methods to measure the more subtle functional morbidities caused by schistosomiasis could be a factor. Further research is needed to identify and develop well-defined, easily quantifiable S. mansoni morbidity markers for this age group.

Phenotypic and Genotypic Antibiotic Resistant diarrheagenic Escherichia coli pathotypes isolated from Children with Diarrhea in Nairobi City, Kenya.

BACKGROUND: The marked genome plasticity of diarrheagenic Escherichia coli promotes emergence of pathotypes displaying unique phenotypic and genotypic resistance. This study examined phenotypic and genotypic antibiotic resistant diarrheagenic Escherichia coli pathotypes among children in Nairobi City, Kenya. METHODS: In a cross-sectional study, diarrheagenic Escherichia coli pathotypes were isolated from stool samples and their phenotypic and genotypic resistance against eight antimicrobial agents assayed. RESULTS: Diarrheagenic Escherichia coli was detected in 136(36.4%) children. Most of diarrheagenic Escherichia coli that were resistant to ampicillin, ceftriaxone, streptomycin, gentamycin, ciprofloxacin, chloramphenicol, erythromycin and tetracycline, harbored citm, bla CMY, aadA1, aac(3)-IV, qnr, catA, ere(A) and tet(A) corresponding resistant genes. CONCLUSION: Antimicrobial-resistant genes are highly prevalent among phenotypic resistant ETEC pathotypes indicating a possibility of horizontal gene transfer in spreading antibiotic resistant genes among E. coli pathotypes.

HIV infection drives IgM and IgG3 subclass bias in Plasmodium falciparum-specific and total immunoglobulin concentration in Western Kenya.

BACKGROUND: HIV infection is associated with more frequent and severe episodes of malaria and may be the result of altered malaria-specific B cell responses. However, it is poorly understood how HIV and the associated lymphopenia and immune activation affect malaria-specific antibody responses. METHODS: HIV infected and uninfected adults were recruited from Bondo subcounty hospital in Western Kenya at the time of HIV testing (antiretroviral and co-trimoxazole prophylaxis naïve). Total and Plasmodium falciparum apical membrane antigen-1 (AMA1) and glutamate rich protein-R0 (GLURP-R0) specific IgM, IgG and IgG subclass concentrations was measured in 129 and 52 of recruited HIV-infected and uninfected individuals, respectively. In addition, HIV-1 viral load (VL), CD4+ T cell count, and C-reactive protein (CRP) concentration was quantified in study participants. Antibody levels were compared based on HIV status and the associations of antibody concentration with HIV-1 VL, CD4+ count, and CRP levels was measured using Spearman correlation testing. RESULTS: Among study participants, concentrations of IgM, IgG1 and IgG3 antibodies to AMA1 and GLURP-R0 were higher in HIV infected individuals compared to uninfected individuals (all p < 0.001). The IgG3 to IgG1 ratio to both AMA1 and GLURP-R0 was also significantly higher in HIV-infected individuals (p = 0.02). In HIV-infected participants, HIV-1 VL and CRP were weakly correlated with AMA1 and GLURP-R0 specific IgM and IgG1 concentrations and total (not antigen specific) IgM, IgG, IgG1, and IgG3 concentrations (all p < 0.05), suggesting that these changes are related in part to viral load and inflammation. CONCLUSIONS: Overall, HIV infection leads to a total and malaria antigen-specific immunoglobulin production bias towards higher levels of IgM, IgG1, and IgG3, and HIV-1 viraemia and systemic inflammation are weakly correlated with these changes. Further assessments of antibody affinity and function and correlation with risk of clinical malaria, will help to better define the effects of HIV infection on clinical and biological immunity to malaria.

Molecular basis of reduced LAIR1 expression in childhood severe malarial anaemia: Implications for leukocyte inhibitory signalling.

BACKGROUND: Leukocyte-associated immunoglobulin like receptor-1 (LAIR1) is a transmembrane inhibitory receptor that influences susceptibility to a myriad of inflammatory diseases. Our recent investigations of severe malarial anaemia (SMA) pathogenesis in Kenyan children discovered that novel LAIR1 genetic variants which were associated with decreased LAIR1 transcripts enhanced the longitudinal risk of SMA and all-cause mortality. METHODS: To characterize the molecular mechanism(s) responsible for altered LAIR1 signalling in severe malaria, we determined LAIR1 transcripts and protein, sLAIR1, sLAIR2, and complement component 1q (C1q) in children with malarial anaemia, followed by a series of in vitro experiments investigating the LAIR1 signalling cascade. FINDINGS: Kenyan children with SMA had elevated circulating levels of soluble LAIR1 (sLAIR1) relative to non-SMA (1.69-fold P < .0001). The LAIR1 antagonist, sLAIR2, was also elevated in the circulation of children with SMA (1.59 fold-change, P < .0001). There was a positive correlation between sLAIR1 and sLAIR2 (ρ = 0.741, P < .0001). Conversely, circulating levels of complement component 1q (C1q), a LAIR1 natural ligand, were lower in SMA (-1.21-fold P = .048). These in vivo findings suggest that reduced membrane-bound LAIR1 expression in SMA is associated with elevated production of sLAIR1, sLAIR2 (antagonist), and limited C1q (agonist) availability. Since reduced LAIR1 transcripts in SMA were associated with increased acquisition of haemozoin (PfHz) by monocytes (P = .028), we explored the relationship between acquisition of intraleukocytic PfHz, LAIR1 expression, and subsequent impacts on leukocyte signalling in cultured PBMCs from malaria-naïve donors stimulated with physiological concentrations of PfHz (10 µg/mL). Phagocytosis of PfHz reduced LAIR1 transcript and protein expression in a time-dependent manner (P < .050), and inhibited LAIR1 signalling through decreased phosphorylation of LAIR1 (P < .0001) and SH2-domain containing phosphatase-1 (SHP-1) (P < .001). This process was associated with NF-κB activation (P < .0001) and enhanced production of IL-6, IL-1ß, and TNF-α (all P < .0001). INTERPRETATION: Collectively, these findings demonstrate that SMA is characterized by reduced LAIR1 transmembrane expression, reduced C1q, and enhanced production of sLAIR1 and sLAIR2, molecular events which can promote enhanced production of cytokines that contribute to the pathogenesis of SMA. These investigations are important for discovering immune checkpoints that could be future targets of immunotherapy to improve disease outcomes.

Integrated OMICS platforms identify LAIR1 genetic variants as novel predictors of cross-sectional and longitudinal susceptibility to severe malaria and all-cause mortality in Kenyan children.

BACKGROUND: Severe malarial anaemia (SMA) is a leading cause of childhood mortality in holoendemic Plasmodium falciparum regions. METHODS: To gain an improved understanding of SMA pathogenesis, whole genome and transcriptome profiling was performed in Kenyan children (n=144, 3-36months) with discrete non-SMA and SMA phenotypes. Leukocyte associated immunoglobulin like receptor 1 (LAIR1) emerged as a predictor of susceptibility to SMA (P<1×10-2, OR: 0.44-1.37), and was suppressed in severe disease (-1.69-fold, P=0.004). To extend these findings, the relationship between LAIR1 polymorphisms [rs6509867 (16231C>A); rs2287827 (18835G>A)] and clinical outcomes were investigated in individuals (n=1512, <5years) at enrolment and during a 36-month longitudinal follow-up. FINDINGS: Inheritance of the 16,231 recessive genotype (AA) increased susceptibility to SMA at enrolment (OR=1.903, 95%CI: 1.252-2.891, P=0.003), and longitudinally (RR=1.527, 95%CI: 1.119-2.083, P=0.008). Carriage of the 18,835 GA genotype protected against SMA cross-sectionally (OR=0.672, 95%CI: 0.480-0.9439, P=0.020). Haplotype carriage (C16231A/G18835A) also altered cross-sectional susceptibility to SMA: CG (OR=0.717, 95%CI: 0.527-0.9675, P=0.034), CA (OR=0.745, 95%CI: 0.536-1.036, P=0.080), and AG (OR=1.641, 95%CI: 1.160-2.321, P=0.005). Longitudinally, CA carriage was protective against SMA (RR=0.715, 95%CI: 0.554-0.923, P=0.010), while AG carriage had an additive effect on enhanced SMA risk (RR=1.283, 95%CI: 1.057-1.557, P=0.011). Variants that protected against SMA had elevated LAIR1 transcripts, while those with enhanced risk had lower expression (P<0.05). Inheritance of 18,835 GA reduced all-cause mortality by 44.8% (HR=0.552, 95%CI: 0.329-0.925, P=0.024), while AG haplotype carriage increased susceptibility by 68% (HR=1.680, 95%CI: 1.020-2.770, P=0.040). INTERPRETATION: These findings suggest LAIR1 is important for modulating susceptibility to SMA and all-cause childhood mortality.

Correction to: Seroprevalence and determinants of transfusion transmissible infections among voluntary blood donors in Homabay, Kisumu and Siaya counties in western Kenya.

Following publication of the original article [1], the authors reported that for two of the authors, Felix Humwa and Vallarie Opollo, an incorrect affiliation has been given. In this Correction the incorrect and correct affiliations are listed.

Seroprevalence and determinants of transfusion transmissible infections among voluntary blood donors in Homabay, Kisumu and Siaya counties in western Kenya.

OBJECTIVE: Since the implementation of a series of blood donation safety improvements in Kenya, information about seroprevalence and determinants of transfusion transmissible infections among voluntary blood donors especially in high HIV burden regions of Homabay, Kisumu and Siaya counties remain scanty. A cross-sectional study examining HIV, syphilis, hepatitis B and C virus sero-markers and associated determinants was conducted among voluntary blood donors. Their demographic characteristics and previous risk exposure were recorded in a pre-donation questionnaire, while blood samples collected were screened for hepatitis B, hepatitis C, human immunodeficiency viruses by ELISA and RPR (syphilis), then confirmed using CMIA. RESULTS: Overall TTIs seroprevalence was 114 (9.4%), distributed among HIV, HBV, HCV and syphilis at 14 (1.15%), 42 (3.46%), 39 (3.21%) and 19 (1.56%), respectively, with co-infections of 3 (0.25%). There were no significant differences in proportions distributions among demographic variables. However, high risk sex was significantly associated with higher odds of HBV infections [> 1 partner vs. 0-1 partner; odd ratio (OR) 2.60; 95% confidence interval (CI) 1.098-6.86; p = 0.046]. In conclusion, a substantial percentage of blood donors still harbor transfusion transmissible infections despite recent safety improvements with greater majority cases caused by HBV infections arising from previous exposure to high risk sex.