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Multidrug-resistant tuberculosis (MDR-TB) is caused by M. tuberculosis (Mtb) with resistance to the first-line anti-TB medicines isoniazid (INH) and rifampicin (RIF). In Western Kenya, there is reported low prevalence of drug resistant strains among HIV tuberculosis patients, creating a need to determine factors associated with drug resistance patterns among presumptive MDR-TB patients. To determine factors associated with drug resistance patterns among presumptive MDR-TB patients in western Kenya. Three hundred and ninety (3 9 0) sputum sample isolates from among presumptive multidrug TB patients, were analyzed for TB drug resistance as per Ministry of Health (MoH) TB program diagnostic algorithm. Frequency and percentages were used to summarize categorical data while median and interquartile range (IQR) were used for continuous data. Multivariable logistic regression was carried out to identify factors associated with TB drug resistance. Out of 390 participants enrolled, 302/390 (77.4 %) were males, with a median age of 34 years. The HIV-infected were 118/390 (30.3 %). Samples included 322 (82.6 %) from presumptive patients, while 68/390 (17.4 %) were either lost to follow-up patients, failures to first-line treatment or newly diagnosed cases. A total of 64/390 (16.4 %) of the isolates had at least some form of drug resistance. Out of 390, 14/390 (3.6 %) had MDR, 12 (3.1 %) were RIF mono-resistance, 34 (8.7 %) had INH, while 4 (1 %) had ethambutol resistance. The category of previously treated patients (those who received or are currently on TB treatment) had a 70 % reduced likelihood of resistance (aOR: 0.30; 95 % CI: 0.13-0.70). In contrast, older age was associated with an increased likelihood of resistance to INH and RIF, with an adjusted odds ratio of 1.04 per year (95 % CI: 1.00-1.08). Prompt MDR-TB diagnosis is essential for appropriate patient care, management, and disease prevention and control. We recommend active surveillance on drug resistant TB in these regions to detect drug resistance patterns for rapid disease management.
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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.
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Antimaláricos , Artemisininas , Educación en Salud , Humanos , Uganda , Artemisininas/uso terapéutico , Femenino , Adulto , Masculino , Antimaláricos/uso terapéutico , Quimioterapia Combinada , Persona de Mediana Edad , Adulto Joven , Malaria/tratamiento farmacológico , Malaria/prevención & control , Conocimientos, Actitudes y Práctica en Salud , Agentes Comunitarios de Salud/educación , AdolescenteRESUMEN
Background: Low- and middle-income countries continue to bear the burden of cervical cancer partly due to low uptake of screening services. Interventions through the media to increase demand for screening services among women of reproductive age (WRA) have not yielded the desired results mainly due to the unidirectional flow of information. The current study evaluated the use of a dialogue-based approach to community health education to improve the demand for cervical cancer screening services among WRA in rural sub-counties in Kisumu County. Methods: This was a mixed-method longitudinal pre and post-intervention study with a control group. The self-reported screening rates were assessed at baseline in both the intervention and control groups followed by dialogue-based community health education in the intervention arm. This was followed by endline screening rates evaluation. The screening rates at baseline and endline were compared followed by a focused group discussion among the leaders of the community units to discuss the contributors to the observed screening rates. The proportion of change in the screening rates was calculated and statistical significance was assessed at p ≤ 0.05. Results: There was a significant increase in the number of WRA reporting to have been screened at the endline in the intervention arm (p = 0.007). The number of those being screened due to the health talks conducted by the Community health volunteers also increased significantly at the endline (p = 0.036). The barriers included; not knowing where to get screened (p < 0.0001), violation of ones' privacy (p < 0.0001), lack of spousal support (p < 0.0001), waiting time at the facility (p = 0.001), attitude of the health providers (p < 0.0001) and cost of transport to the facility (p < 0.0001). Conclusion: The use of dialogue-based community health education has the potential to improve the uptake of cervical cancer screening services and identify the additional barriers as experienced by the WRA targeted for screening.
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Single nucleotide polymorphisms (SNPs) in the Plasmodium falciparum multi-drug resistance protein 1 (Pfmrp1) gene have previously been reported to confer resistance to Artemisinin-based Combination Therapies (ACTs) in Southeast Asia. A total of 300 samples collected from six sites between 2008 and 2019 under an ongoing malaria drug sensitivity patterns in Kenya study were evaluated for the presence of SNPs at Pfmrp1 gene codons: H191Y, S437A, I876V, and F1390I using the Agena MassARRAY® platform. Each isolate was further tested against artemisinin (ART), lumefantrine (LU), amodiaquine (AQ), mefloquine (MQ), quinine (QN), and chloroquine (CQ) using malaria the SYBR Green I-based method to determine their in vitro drug sensitivity. Of the samples genotyped, polymorphism at Pfmrp1 codon I876V was the most frequent, with 59.3% (163/275) mutants, followed by F1390I, 7.2% (20/278), H191Y, 4.0% (6/151), and S437A, 3.3% (9/274). A significant decrease in median 50% inhibition concentrations (IC50s) and interquartile range (IQR) was noted; AQ from 2.996 ng/ml [IQR = 2.604-4.747, n = 51] in 2008 to 1.495 ng/ml [IQR = 0.7134-3.318, n = 40] (P<0.001) in 2019, QN from 59.64 ng/ml [IQR = 29.88-80.89, n = 51] in 2008 to 18.10 ng/ml [IQR = 11.81-26.92, n = 42] (P<0.001) in 2019, CQ from 35.19 ng/ml [IQR = 16.99-71.20, n = 30] in 2008 to 6.699 ng/ml [IQR = 4.976-9.875, n = 37] (P<0.001) in 2019, and ART from 2.680 ng/ml [IQR = 1.608-4.857, n = 57] in 2008 to 2.105 ng/ml [IQR = 1.266-3.267, n = 47] (P = 0.0012) in 2019, implying increasing parasite sensitivity to the drugs over time. However, no significant variations were observed in LU (P = 0.2692) and MQ (P = 0.0939) respectively, suggesting stable parasite responses over time. There was no statistical significance between the mutation at 876 and parasite sensitivity to selected antimalarials tested, suggesting stable sensitivity for the parasites with 876V mutations. These findings show that Kenyan parasite strains are still sensitive to AQ, QN, CQ, ART, LU, and MQ. Despite the presence of Pfmrp1 mutations in parasites among the population.
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Antimaláricos , Combinación Arteméter y Lumefantrina , Malaria Falciparum , Plasmodium falciparum , Polimorfismo de Nucleótido Simple , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Humanos , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/genética , Combinación Arteméter y Lumefantrina/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/parasitología , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Kenia , Mefloquina/farmacología , Mefloquina/uso terapéutico , Amodiaquina/farmacología , Amodiaquina/uso terapéutico , Resistencia a Medicamentos/genética , Artemisininas/farmacología , Artemisininas/uso terapéutico , Cloroquina/farmacología , Cloroquina/uso terapéutico , Quinina/farmacología , Quinina/uso terapéutico , Masculino , FemeninoRESUMEN
This study on severe malarial anemia (SMA: Hb < 6.0 g/dL), a leading global cause of childhood morbidity and mortality, compares the entire expressed whole blood host transcriptome between Kenyan children (3-48 mos.) with non-SMA (Hb ≥ 6.0 g/dL, n = 39) and SMA (n = 18). Differential expression analyses reveal 1403 up-regulated and 279 down-regulated transcripts in SMA, signifying impairments in host inflammasome activation, cell death, and innate immune and cellular stress responses. Immune cell profiling shows decreased memory responses, antigen presentation, and immediate pathogen clearance, suggesting an immature/improperly regulated immune response in SMA. Module repertoire analysis of blood-specific gene signatures identifies up-regulation of erythroid genes, enhanced neutrophil activation, and impaired inflammatory responses in SMA. Enrichment analyses converge on disruptions in cellular homeostasis and regulatory pathways for the ubiquitin-proteasome system, autophagy, and heme metabolism. Pathway analyses highlight activation in response to hypoxic conditions [Hypoxia Inducible Factor (HIF)-1 target and Reactive Oxygen Species (ROS) signaling] as a central theme in SMA. These signaling pathways are also top-ranking in protein abundance measures and a Ugandan SMA cohort with available transcriptomic data. Targeted RNA-Seq validation shows strong concordance with our entire expressed transcriptome data. These findings identify key molecular themes in SMA pathogenesis, offering potential targets for new malaria therapies.
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Anemia , Transcriptoma , Humanos , Anemia/genética , Anemia/sangre , Preescolar , Lactante , Femenino , Malaria/sangre , Malaria/genética , Kenia , Masculino , Perfilación de la Expresión Génica , Inmunidad Innata/genética , Especies Reactivas de Oxígeno/metabolismo , Especies Reactivas de Oxígeno/sangreRESUMEN
BACKGROUND: Cervical cancer is a leading cause of cancer death among women of reproductive age despite being treatable if it is diagnosed early. Early diagnosis is possible through regular screening through the public health system. However, screening rates remain low in many low- and middle-income countries, including Kenya, where the screening rate currently stands at 16-18%. The low screening rates are attributed to, among other factors, low knowledge about cervical cancer and the available screening options among women of reproductive age. The current study evaluated the effectiveness of dialogue-based community health education by trained community health volunteers (CHVs) in improving cervical cancer knowledge among women of reproductive age (WRA) in rural Kisumu County. METHODS: This was a longitudinal pre- and post-intervention study with a control group. The knowledge of women of reproductive age was assessed at baseline in both the intervention and control groups, followed by dialogue-based community health education in the intervention arm. A final end-line knowledge assessment was performed. The scores at baseline and at the end of the study were compared to assess changes in knowledge due to the intervention. The proportion of WRA with improved knowledge was also calculated, and statistical significance was considered at p ≤ 0.05. RESULTS: There was no significant difference between the participants in the two arms, except for the level of education (p = 0.002). The knowledge of the WRA in the intervention arm improved significantly (p < 0.001) following the dialogue-based educational intervention by the trained CHVs. None of the demographic characteristics were associated with knowledge. CONCLUSION: Dialogue-based educational intervention significantly improved the knowledge of the WRA in the intervention arm, showing its potential to address the knowledge gap in the community.
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Agentes Comunitarios de Salud , Educación en Salud , Conocimientos, Actitudes y Práctica en Salud , Población Rural , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control , Kenia , Adulto , Educación en Salud/métodos , Estudios Longitudinales , Agentes Comunitarios de Salud/educación , Persona de Mediana Edad , Detección Precoz del Cáncer/métodos , Adulto Joven , AdolescenteRESUMEN
Vaccination is crucial in reducing child mortality and the prevalence of Vaccine-Preventable-Diseases (VPD), especially in low-and-middle-income countries like Kenya. However, non-vaccination, under-vaccination, and missed opportunities for vaccination (MOV) pose significant challenges to these efforts. This study aimed to analyze the impact of demographic and socio-economic factors on non-vaccination, under-vaccination, and MOV among children aged 0-23 months in Kenya from 2003 to 2014. A secondary data analysis of data from the Kenya Demographic Health Surveys (KDHS) conducted during this period was conducted, with a total of 11,997 participants, using a two-stage, multi-stage, and stratified sampling technique. The study examined factors such as child's sex, residence, mother's age, marital status, religion, birth order, maternal education, wealth quintile, province, child's birth order, parity, number of children in the household, place of delivery, and mother's occupation. Binary logistic regression was employed to identify the determinants of non-vaccination, under-vaccination, and MOV, and multivariable logistic regression analysis to report odds ratios (OR) and their corresponding 95% confidence intervals (CI). In 2003, the likelihood of non-vaccination decreased with higher maternal education levels: mothers who did not complete primary education (AOR = 0.55, 95% CI = 0.37-0.81), completed primary education (AOR = 0.34, 95% CI = 0.21-0.56), and had secondary education or higher (AOR = 0.26, 95% CI = 0.14-0.50) exhibited decreasing probabilities. In 2008/09, divorced/separated/widowed mothers (AOR = 0.22, 95% CI = 0.07-0.65) and those with no religion (AOR = 0.37, 95% CI = 0.17-0.81) showed lower odds of non-vaccination, while lower wealth quintiles were associated with higher odds. In 2014, non-vaccination was higher among younger mothers aged 15-19 years (AOR = 12.53, 95% CI = 1.59-98.73), in North Eastern Province (AOR = 7.15, 95% CI = 2.02-25.30), in families with more than 5 children (AOR = 4.19, 95% CI = 1.09-16.18), and in children born at home (AOR = 4.47, 95% CI = 1.32-15.17). Similar patterns were observed for under-vaccination and MOV. This information can inform strategies for bridging the gaps in immunization coverage and promoting equitable vaccination practices in Kenya.
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BACKGROUND: Community and individual participation are crucial for the success of schistosomiasis control. The World Health Organization (WHO) has highlighted the importance of enhanced sanitation, health education, and Mass Drug Administration (MDA) in the fight against schistosomiasis. These approaches rely on the knowledge and practices of the community to be successful; however, where the community knowledge is low and inappropriate, it hinders intervention efforts. Hence, it is essential to identify barriers and misconceptions related to awareness of schistosomiasis, sources of infection, mode of transmission, symptoms, and control measures. METHODS: This was a mixed-method cross-sectional study involving 1200 pre-school children randomly selected and examined for Schistosoma mansoni infection using the Kato-Katz technique. All parents/guardians of selected children were enrolled for a pre-tested questionnaire survey, while 42 were engaged in focus group discussions (FGDs). The level of knowledge and awareness among parents/guardians about schistosomiasis was evaluated in relation to the infection status of their pre-school children. RESULTS: Among pre-school children, the prevalence of intestinal schistosomiasis was 45.1% (95% CI 41.7-48.5). A majority of parents/guardians (85.5%) had heard about schistosomiasis, and this awareness was associated with the participant's level of education (OR = 0.16, 95% CI 0.08, 0.34). In addition, a positive association was observed between higher educational attainment and knowledge of the causative agent (OR = 0.69, 95% CI 0.49, 0.96). Low education level was significantly associated with limited knowledge of transmission through lake water contact (OR = 0.71, 95% CI 0.52, 0.97) and infection from the lake (OR = 0.33, 95% CI 0.19, 0.57). Notably, parents/guardians who have heard of schistosomiasis could not recognize symptoms of S. mansoni infection, such as abdominal pain (91.8%, 815/888) and blood in the stool (85.1%, 756/888). Surprisingly, 49.8% (442/888) incorrectly identified hematuria (blood in urine), a key sign of S. haematobium, but not S. mansoni, in an endemic area for S. mansoni infection. The majority (82.6%, 734/888) of parents/guardians were unaware that dams are potential infection sites, despite 53.9% (479/888) of their pre-school-aged children testing positive for schistosome infection. CONCLUSIONS: Despite the high level of awareness of intestinal schistosomiasis in the study area, we identified a low level of knowledge regarding its causes, modes of transmission, signs and symptoms and potential sites of transmission within the community. This study emphasizes the need for targeted educational interventions to address the misconceptions and knowledge gaps surrounding intestinal schistosomiasis through tailored community-based programs.
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BACKGROUND: Vector surveillance is among the World Health Organization global vector control response (2017-2030) pillars. Human landing catches are a gold standard but difficult to implement and potentially expose collectors to malaria infection. Other methods like light traps, pyrethrum spray catches and aspiration are less expensive and less risky to collectors. METHODS: Three mosquito sampling methods (UV light traps, CDC light traps and Prokopack aspiration) were evaluated against human landing catches (HLC) in two villages of Rarieda sub-county, Siaya County, Kenya. UV-LTs, CDC-LTs and HLCs were conducted hourly between 17:00 and 07:00. Aspiration was done indoors and outdoors between 07:00 and 11:00 a.m. Analyses of mosquito densities, species abundance and sporozoite infectivity were performed across all sampling methods. Species identification PCR and ELISAs were done for Anopheles gambiae and Anopheles funestus complexes and data analysis was done in R. RESULTS: Anopheles mosquitoes sampled from 608 trapping efforts were 5,370 constituting 70.3% Anopheles funestus sensu lato (s.l.), 19.7% Anopheles coustani and 7.2% An. gambiae s.l. 93.8% of An. funestus s.l. were An. funestus sensu stricto (s.s.) and 97.8% of An. gambiae s.l. were Anopheles arabiensis. Only An. funestus were sporozoite positive with 3.1% infection prevalence. Indoors, aspiration captured higher An. funestus (mean = 6.74; RR = 8.83, P < 0.001) then UV-LT (mean = 3.70; RR = 3.97, P < 0.001) and CDC-LT (mean = 1.74; RR = 1.89, P = 0.03) compared to HLC. UV-LT and CDC-LT indoors captured averagely 0.18 An. arabiensis RR = 5.75, P = 0.028 and RR = 5.87, P = 0.028 respectively. Outdoors, UV-LT collected significantly higher Anopheles mosquitoes compared to HLC (An. funestus: RR = 5.18, P < 0.001; An. arabiensis: RR = 15.64, P = 0.009; An. coustani: RR = 11.65, P < 0.001). Anopheles funestus hourly biting indoors in UV-LT and CDC-LT indicated different peaks compared to HLC. CONCLUSIONS: Anopheles funestus remains the predominant mosquito species. More mosquitoes were collected using aspiration, CDC-LTs and UV-LTs indoors and UV-LTs and CD-LTs outdoors compared to HLCs. UV-LTs collected more mosquitoes than CDC-LTs. The varied trends observed at different times of the night suggest that these methods collect mosquitoes with diverse activities and care must be taken when interpreting the results.
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Anopheles , Malaria , Animales , Humanos , Anopheles/fisiología , Kenia/epidemiología , Mosquitos Vectores/fisiología , Conducta Alimentaria , Esporozoítos , Control de Mosquitos/métodosRESUMEN
Vaccines are effective and cost-effective. Non-vaccination, under-vaccination, and missed opportunities for vaccination (MOV), have contributed to incomplete vaccination coverage in Kenya. Analyzing their trends is essential for targeting interventions and improvement strategies. This study aimed to assess trends of non-vaccination, under-vaccination, and MOV among children aged 0-23 months in Kenya using data obtained from the Kenya Demographic and Health Surveys (KDHS) conducted in 2003, 2008/09, and 2014. A two-stage, multi-stage, and stratified sampling technique was used. Weighted analysis was conducted to ensure generalizability to the full population. Using the KDHS sample size estimation process, the sample size was estimated for each indicator, with varying standard error estimates, level of coverage and estimated response rates. Final sample size was 2380 (2003), 2237 (2008/09) and 7380 (2014). To determine the level of non-vaccination, under-vaccination and MOV among children aged 0-23 months, a weighted descriptive analysis was used to estimate their prevalence, with 95% confidence intervals (CI) for each year. MOV was defined using an algorithm as a binary variable. Data coding and recoding were done using Stata (version 14; College Station, TX: StataCorp LP). Trends in proportions of non-vaccination, under-vaccination and MOV were compared between 2003, 2008/09, and 2014 using the Cochrane-Armitage trend test. All results with P≤0.05 were considered statistically significant. Trends in proportion of non-vaccination among children aged 0-23 months in Kenya was 13.2%, 6.1% and 3.2% in 2003, 2008/09 and 2014, respectively (P = 0.0001). Trends in proportion of under-vaccination among children aged 0-23 months in Kenya was 54.3%, 50% and 51.3% in 2003, 2008/09 and 2014, respectively (P = 0.0109). The trends in proportion of children who experienced MOV was 22.7% in 2003, 31.9% in 2008/09 and 37.6% in 2014 (P = 0.0001). In the study duration, non-vaccination decreased by 10%, under-vaccination remained relatively stable, and MOV increased by ~15%. There is need for the Government and partners to implement initiatives that improve vaccine access and coverage, particularly in regions with low coverage rates, and to address missed opportunities for vaccination.
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BACKGROUND: Food insecurity is a major predicament for rural populations, especially mothers and children, whose livelihoods are often dependent on rain-fed agriculture. Indigenous foods have the potential of mitigating food insecurity as they can thrive in poor agro-ecological conditions. However, the associations between indigenous food production and food security status of mothers and children drawn from rural contexts has not been expansively assessed. Food insecurity evident by high food poverty rates remain high in Kisumu County due to over-reliance on food imports from other counties. The objective of the study was to assess seasonality in associations between production of selected indigenous foods (kidney beans, soya beans, millet, cassava, sweet potatoes, groundnuts, green grams, cow peas, amaranth leaves, spider plant leaves, black night shade leaves, mangoes, guavas, lime, and tamarind) and food security status of mothers and children during planting and harvesting seasons. METHODS: We used a longitudinal study design adopting both quantitative and qualitative data collection methods. A structured questionnaire assessed production of selected indigenous foods in the sampled households, Household Food Insecurity Access Scale for mother's food security status and Prevalence of Underweight for children's food security status. Ordinal logistic regression was used to derive odds ratio (OR), which assessed strength of associations between dependent variables (mother's and children's food security status) and independent variables (production of selected indigenous foods). Significance was determined at α ≤ 0.05. RESULTS: Results demonstrated that during planting season, production of kidney beans decreased the odds of mothers being severely food insecure by 53% (OR = 0.469, 95% CI = 0.228-0.964, p = 0.039). In the same season, sorghum production demonstrated 3.5 times increase in odds of children being severely food insecure (OR = 3.498, 95% CI = 1.454-8.418, p = 0.005). During harvesting season, production of kidney beans was associated with a 62% reduction in the odds of children being severely food insecure (OR = 0.379, 95% CI = 0.190-0.754, p = 0.006). CONCLUSIONS: Production of some of the selected indigenous foods demonstrated significant odds of predicting mother's and children's food security status across both study seasons. An intervention-based study approach that would best establish causal associations of indigenous food production and food security status is recommended.
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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.
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Antimaláricos , Artemisininas , Malaria , Femenino , Humanos , Adulto Joven , Adulto , Masculino , Uganda , Estudios Longitudinales , Artemisininas/uso terapéutico , Malaria/tratamiento farmacológico , Malaria/prevención & control , Malaria/epidemiología , Antimaláricos/uso terapéutico , Combinación de Medicamentos , Quimioterapia CombinadaRESUMEN
INTRODUCTION: Global morbidity from enteric infections and diarrhoea remains high in children in low-income and middle-income countries, despite significant investment over recent decades in health systems and water and sanitation infrastructure. Other types of societal development may be required to reduce disease burden. Ecological research on the influence of household and neighbourhood societal development on pathogen transmission dynamics between humans, animals and the environment could identify more effective strategies for preventing enteric infections. METHODS AND ANALYSIS: The 'enteric pathome'-that is, the communities of viral, bacterial and parasitic pathogens transmitted from human and animal faeces through the environment is taxonomically complex in high burden settings. This integrated cohort-exposure assessment study leverages natural socioeconomic spectrums of development to study how pathome complexity is influenced by household and neighbourhood infrastructure and hygiene conditions. We are enrolling under 12-month-old children in low-income and middle-income neighbourhoods of two Kenyan cities (Nairobi and Kisumu) into a 'short-cohort' study involving repeat testing of child faeces for enteric pathogens. A mid-study exposure assessment documenting infrastructural, behavioural, spatial, climate, environmental and zoonotic factors characterises pathogen exposure pathways in household and neighbourhood settings. These data will be used to inform and validate statistical and agent-based models (ABM) that identify individual or combined intervention strategies for reducing multipathogen transmission between humans, animals and environment in urban Kenya. ETHICS AND DISSEMINATION: The protocols for human subjects' research were approved by Institutional Review Boards at the University of Iowa (ID-202004606) and AMREF Health Africa (ID-ESRC P887/2020), and a national permit was obtained from the Kenya National Commission for Science Technology and Innovation (ID# P/21/8441). The study was registered on Clinicaltrials.gov (Identifier: NCT05322655) and is in pre-results stage. Protocols for research on animals were approved by the University of Iowa Animal Care and Use Committee (ID 0042302).
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Animales Domésticos , Diarrea , Niño , Animales , Lactante , Humanos , Estudios de Cohortes , Kenia/epidemiología , Diarrea/prevención & control , SaneamientoRESUMEN
BACKGROUND: Plasmodium falciparum malaria is a leading cause of pediatric morbidity and mortality in holoendemic transmission areas. Severe malarial anemia [SMA, hemoglobin (Hb) < 5.0 g/dL in children] is the most common clinical manifestation of severe malaria in such regions. Although innate immune response genes are known to influence the development of SMA, the role of natural killer (NK) cells in malaria pathogenesis remains largely undefined. As such, we examined the impact of genetic variation in the gene encoding a primary NK cell receptor, natural cytotoxicity-triggering receptor 3 (NCR3), on the occurrence of malaria and SMA episodes over time. METHODS: Susceptibility to malaria, SMA, and all-cause mortality was determined in carriers of NCR3 genetic variants (i.e., rs2736191:C > G and rs11575837:C > T) and their haplotypes. The prospective observational study was conducted over a 36 mos. follow-up period in a cohort of children (n = 1,515, aged 1.9-40 mos.) residing in a holoendemic P. falciparum transmission region, Siaya, Kenya. RESULTS: Poisson regression modeling, controlling for anemia-promoting covariates, revealed a significantly increased risk of malaria in carriers of the homozygous mutant allele genotype (TT) for rs11575837 after multiple test correction [Incidence rate ratio (IRR) = 1.540, 95% CI = 1.114-2.129, P = 0.009]. Increased risk of SMA was observed for rs2736191 in children who inherited the CG genotype (IRR = 1.269, 95% CI = 1.009-1.597, P = 0.041) and in the additive model (presence of 1 or 2 copies) (IRR = 1.198, 95% CI = 1.030-1.393, P = 0.019), but was not significant after multiple test correction. Modeling of the haplotypes revealed that the CC haplotype had a significant additive effect for protection against SMA (i.e., reduced risk for development of SMA) after multiple test correction (IRR = 0.823, 95% CI = 0.711-0.952, P = 0.009). Although increased susceptibility to SMA was present in carriers of the GC haplotype (IRR = 1.276, 95% CI = 1.030-1.581, P = 0.026) with an additive effect (IRR = 1.182, 95% CI = 1.018-1.372, P = 0.029), the results did not remain significant after multiple test correction. None of the NCR3 genotypes or haplotypes were associated with all-cause mortality. CONCLUSIONS: Variation in NCR3 alters susceptibility to malaria and SMA during the acquisition of naturally-acquired malarial immunity. These results highlight the importance of NK cells in the innate immune response to malaria.
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Anemia , Malaria Falciparum , Malaria , Humanos , Niño , Anemia/genética , Genotipo , Malaria Falciparum/genética , Alelos , Receptor 3 Gatillante de la Citotoxidad NaturalRESUMEN
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.
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This study on severe malarial anemia (SMA: Hb < 6.0 g/dL), a leading global cause of childhood morbidity and mortality, analyzed the entire expressed transcriptome in whole blood from children with non-SMA (Hb ≥ 6.0 g/dL, n = 41) and SMA (n = 25). Analyses revealed 3,420 up-regulated and 3,442 down-regulated transcripts, signifying impairments in host inflammasome activation, cell death, innate immune responses, and cellular stress responses in SMA. Immune cell profiling showed a decreased antigenic and immune priming response in children with SMA, favoring polarization toward cellular proliferation and repair. Enrichment analysis further identified altered neutrophil and autophagy-related processes, consistent with neutrophil degranulation and altered ubiquitination and proteasome degradation. Pathway analyses highlighted SMA-related alterations in cellular homeostasis, signaling, response to environmental cues, and cellular and immune stress responses. Validation with a qRT-PCR array showed strong concordance with the sequencing data. These findings identify key molecular themes in SMA pathogenesis, providing potential targets for new malaria therapies.
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BACKGROUND: Epstein Barr virus (EBV)-associated endemic Burkitt's Lymphoma pediatric cancer is associated with morbidity and mortality among children resident in holoendemic Plasmodium falciparum regions in western Kenya. P. falciparum exerts strong selection pressure on sickle cell trait (SCT), alpha thalassemia (-α3.7/αα), glucose-6-phosphate dehydrogenase (G6PD), and merozoite surface protein 2 (MSP-2) variants (FC27, 3D7) that confer reduced malarial disease severity. The current study tested the hypothesis that SCT, (-α3.7/αα), G6PD mutation and (MSP-2) variants (FC27, 3D7) are associated with an early age of EBV acquisition. METHODS: Data on infant EBV infection status (< 6 and ≥ 6-12 months of age) was abstracted from a previous longitudinal study. Archived infant DNA (n = 81) and mothers DNA (n = 70) samples were used for genotyping hemoglobinopathies and MSP-2. The presence of MSP-2 genotypes in maternal DNA samples was used to indicate infant in-utero malarial exposure. Genetic variants were determined by TaqMan assays or standard PCR. Group differences were determined by Chi-square or Fisher's analysis. Bivariate regression modeling was used to determine the relationship between the carriage of genetic variants and EBV acquisition. RESULTS: EBV acquisition for infants < 6 months was not associated with -α3.7/αα (OR = 1.824, P = 0.354), SCT (OR = 0.897, P = 0.881), or G6PD [Viangchan (871G > A)/Chinese (1024 C > T) (OR = 2.614, P = 0.212)] and [Union (1360 C > T)/Kaiping (1388G > A) (OR = 0.321, P = 0.295)]. There was no relationship between EBV acquisition and in-utero exposure to either FC27 (OR = 0.922, P = 0.914) or 3D7 (OR = 0.933, P = 0.921). In addition, EBV acquisition in infants ≥ 6-12 months also showed no association with -α3.7/αα (OR = 0.681, P = 0.442), SCT (OR = 0.513, P = 0.305), G6PD [(Viangchan (871G > A)/Chinese (1024 C > T) (OR = 0.640, P = 0.677)], [Mahidol (487G > A)/Coimbra (592 C > T) (OR = 0.948, P = 0.940)], [(Union (1360 C > T)/Kaiping (1388G > A) (OR = 1.221, P = 0.768)], African A (OR = 0.278, P = 0.257)], or in utero exposure to either FC27 (OR = 0.780, P = 0.662) or 3D7 (OR = 0.549, P = 0.241). CONCLUSION: Although hemoglobinopathies (-α3.7/αα, SCT, and G6PD mutations) and in-utero exposure to MSP-2 were not associated with EBV acquisition in infants 0-12 months, novel G6PD variants were discovered in the population from western Kenya. To establish that the known and novel hemoglobinopathies, and in utero MSP-2 exposure do not confer susceptibility to EBV, future studies with larger sample sizes from multiple sites adopting genome-wide analysis are required.
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Infecciones por Virus de Epstein-Barr , Hemoglobinopatías , Malaria Falciparum , Malaria , Niño , Animales , Humanos , Lactante , Herpesvirus Humano 4/genética , Merozoítos , Infecciones por Virus de Epstein-Barr/epidemiología , Infecciones por Virus de Epstein-Barr/genética , Kenia/epidemiología , Malaria/epidemiología , Malaria/genética , Polimorfismo GenéticoRESUMEN
Background: Severe malarial anemia (SMA; Hb < 5.0 g/dl) is a leading cause of childhood morbidity and mortality in holoendemic Plasmodium falciparum transmission regions such as western Kenya. Methods: We investigated the relationship between two novel complement component 5 (C5) missense mutations [rs17216529:C>T, p(Val145Ile) and rs17610:C>T, p(Ser1310Asn)] and longitudinal outcomes of malaria in a cohort of Kenyan children (under 60 mos, n = 1,546). Molecular modeling was used to investigate the impact of the amino acid transitions on the C5 protein structure. Results: Prediction of the wild-type and mutant C5 protein structures did not reveal major changes to the overall structure. However, based on the position of the variants, subtle differences could impact on the stability of C5b. The influence of the C5 genotypes/haplotypes on the number of malaria and SMA episodes over 36 months was determined by Poisson regression modeling. Genotypic analyses revealed that inheritance of the homozygous mutant (TT) for rs17216529:C>T enhanced the risk for both malaria (incidence rate ratio, IRR = 1.144, 95%CI: 1.059-1.236, p = 0.001) and SMA (IRR = 1.627, 95%CI: 1.201-2.204, p = 0.002). In the haplotypic model, carriers of TC had increased risk of malaria (IRR = 1.068, 95%CI: 1.017-1.122, p = 0.009), while carriers of both wild-type alleles (CC) were protected against SMA (IRR = 0.679, 95%CI: 0.542-0.850, p = 0.001). Conclusion: Collectively, these findings show that the selected C5 missense mutations influence the longitudinal risk of malaria and SMA in immune-naïve children exposed to holoendemic P. falciparum transmission through a mechanism that remains to be defined.
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BACKGROUND: Malaria remains a public health problem in Kenya despite sustained interventions deployed by the government. One of the major impediments to effective malaria control is a lack of accurate diagnosis and effective treatment. This study was conducted to assess clinical malaria incidence and treatment seeking profiles of febrile cases in western Kenya. METHODS: Active case detection of malaria was carried out in three eco-epidemiologically distinct zones topologically characterized as lakeshore, hillside, and highland plateau in Kisumu County, western Kenya, from March 2020 to March 2021. Community Health Volunteers (CHVs) conducted biweekly visits to residents in their households to interview and examine for febrile illness. A febrile case was defined as an individual having fever (axillary temperature ≥ 37.5 °C) during examination or complaints of fever and other nonspecific malaria related symptoms 1-2 days before examination. Prior to the biweekly malaria testing by the CHVs, the participants' treatment seeking methods were based on their behaviors in response to febrile illness. In suspected malaria cases, finger-prick blood samples were taken and tested for malaria parasites with ultra-sensitive Alere® malaria rapid diagnostic tests (RDT) and subjected to real-time polymerase chain reaction (RT-PCR) for quality control examination. RESULTS: Of the total 5838 residents interviewed, 2205 residents had high temperature or reported febrile illness in the previous two days before the visit. Clinical malaria incidence (cases/1000people/month) was highest in the lakeshore zone (24.3), followed by the hillside (18.7) and the highland plateau zone (10.3). Clinical malaria incidence showed significant difference across gender (χ2 = 7.57; df = 2, p = 0.0227) and age group (χ2 = 58.34; df = 4, p < 0.0001). Treatment seeking patterns of malaria febrile cases showed significant difference with doing nothing (48.7%) and purchasing antimalarials from drug shops (38.1%) being the most common health-seeking pattern among the 2205 febrile residents (χ2 = 21.875; df = 4, p < 0.0001). Caregivers of 802 school-aged children aged 5-14 years with fever primarily sought treatment from drug shops (28.9%) and public hospitals (14.0%), with significant lower proportions of children receiving treatment from traditional medication (2.9%) and private hospital (4.4%) (p < 0.0001). There was no significant difference in care givers' treatment seeking patterns for feverish children under the age of five (p = 0.086). Residents with clinical malaria cases in the lakeshore and hillside zones sought treatment primarily from public hospitals (61.9%, 60/97) traditional medication (51.1%, 23/45) respectively (p < 0.0001). However, there was no significant difference in the treatment seeking patterns of highland plateau residents with clinical malaria (p = 0.431).The main factors associated with the decision to seek treatment were the travel distance to the health facility, the severity of the disease, confidence in the treatment, and affordability. CONCLUSION: Clinical malaria incidence remains highest in the Lakeshore (24.3cases/1000 people/month) despite high LLINs coverage (90%). The travel distance to the health facility, severity of disease and affordability were mainly associated with 80% of residents either self-medicating or doing nothing to alleviate their illness. The findings of this study suggest that the Ministry of Health should strengthen community case management of malaria by providing supportive supervision of community health volunteers to advocate for community awareness, early diagnosis, and treatment of malaria.
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Antimaláricos , Malaria , Antimaláricos/uso terapéutico , Niño , Fiebre/tratamiento farmacológico , Fiebre/epidemiología , Fiebre/etiología , Humanos , Incidencia , Recién Nacido , Kenia/epidemiología , Malaria/diagnóstico , Malaria/tratamiento farmacológico , Malaria/epidemiologíaRESUMEN
BACKGROUND: Identification and characterization of larval habitats, documentation of Anopheles spp. composition and abundance, and Plasmodium spp. infection burden are critical components of integrated vector management. The present study aimed to investigate the effect of landscape heterogeneity on entomological and parasitological indices of malaria in western Kenya. METHODS: A cross-sectional entomological and parasitological survey was conducted along an altitudinal transect in three eco-epidemiological zones: lakeshore along the lakeside, hillside, and highland plateau during the wet and dry seasons in 2020 in Kisumu County, Kenya. Larval habitats for Anopheles mosquitoes were identified and characterized. Adult mosquitoes were sampled using pyrethrum spray catches (PSC). Finger prick blood samples were taken from residents and examined for malaria parasites by real-time PCR (RT-PCR). RESULTS: Increased risk of Plasmodium falciparum infection was associated with residency in the lakeshore zone, school-age children, rainy season, and no ITNs (χ2 = 41.201, df = 9, P < 0.0001). Similarly, lakeshore zone and the rainy season significantly increased Anopheles spp. abundance. However, house structures such as wall type and whether the eave spaces were closed or open, as well as the use of ITNs, did not affect Anopheles spp. densities in the homes (χ2 = 38.695, df = 7, P < 0.0001). Anopheles funestus (41.8%) and An. arabiensis (29.1%) were the most abundant vectors in all zones. Sporozoite prevalence was 5.6% and 3.2% in the two species respectively. The lakeshore zone had the highest sporozoite prevalence (4.4%, 7/160) and inoculation rates (135.2 infective bites/person/year). High larval densities were significantly associated with lakeshore zone and hillside zones, animal hoof prints and tire truck larval habitats, wetland and pasture land, and the wet season. The larval habitat types differed significantly across the landscape zones and seasonality (χ2 = 1453.044, df = 298, P < 0.0001). CONCLUSION: The empirical evidence on the impact of landscape heterogeneity and seasonality on vector densities, parasite transmission, and Plasmodium infections in humans emphasizes the importance of tailoring specific adaptive environmental management interventions to specific landscape attributes to have a significant impact on transmission reduction.