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    Evaluation of a financial incentive intervention on malaria prevalence among the residents in Lake Victoria basin, Kenya: study protocol for a cluster-randomized controlled trial

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    In the Lake Victoria basin of western Kenya, malaria remains highly endemic despite high coverage of interventions such as mass distribution of long-lasting insecticidal nets (LLIN), indoor residual spraying (IRS) programs, and improvement of availability and accessibility of rapid diagnostic tests (RDT) and artemisinin-based combination therapy (ACT) at community healthcare facilities. We hypothesize that one major cause of the residual transmission is the lack of motivation among residents for malaria prevention and early treatment. Methods This study will aim to develop a demand-side policy tool to encourage local residents’ active malaria prevention and early treatment-seeking behaviors. We examine the causal impact of a financial incentive intervention complemented with malaria education to residents in malaria-prone areas. A cluster-randomized controlled trial is designed to assess the effect of the financial incentive intervention on reducing malaria prevalence in residents of Suba South in Homa Bay County, Kenya. The intervention includes two components. The first component is the introduction of a financial incentive scheme tied to negative RDT results for malaria infection among the target population. This study is an attempt to promote behavioral changes in the residents by providing them with monetary incentives. The project has two different forms of incentive schemes. One is a conditional cash transfer (CCT) that offers a small reward (200 Ksh) for non-infected subjects during the follow-up survey, and the other is a lottery incentive scheme (LIS) that gives a lottery with a 10% chance of winning a large reward (2000 Ksh) instead of the small reward. The second component is a knowledge enhancement with animated tablet-based malaria educational material (EDU) developed by the research team. It complements the incentive scheme by providing the appropriate knowledge to the residents for malaria elimination. We evaluate the intervention’s impact on the residents’ malaria prevalence using a cluster-randomized control trial.AK and JG received support from JICA/AMED joint research project (SATREPS) (Grant no. 20JM0110020H0002). TM received support from JSPS KAKENHI (Grant Number JP21H051080). The funding bodies play no role in the study design, data collection, analysis, interpretation, and publication

    Non-Random Distribution of Plasmodium Species Infections and Associated Clinical Features in Children in The Lake Victoria Region, Kenya, 2012-2018

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    Background While Plasmodium falciparum (Pf) stands out as the most lethal malaria parasite species in humans, the impact of other species should not be dismissed. Moreover, there is a notable lack of understanding of mixed-species infections and their clinical implications. Methods We conducted eight school-based cross-sectional malariometric surveys in the Lake Victoria region of western Kenya between 2012 and 2018. Plasmodium infection was determined by microscopy and nested polymerase chain reaction (PCR). The multiple-kind lottery (MKL) model calculated the expected distribution of Plasmodium infections in the population and compared it to observed values using a chi-squared test (χ2). Results The Plasmodium prevalence by PCR was 51.1% (4969/9724). Among all infections, Pf, P. malariae (Pm), and P. ovale (Po) mono-infections were 58.6%, 3.0%, and 1.7%, respectively. Pf/Pm, Pf/Po, Pm/Po, and Pf/Pm/Po co-infections were 23.5%, 4.3%, 0.1%, and 8.6%, respectively. MKL modelling revealed non-random distributions with frequencies of Pf/Pm and Pf/Pm/Po co-infections higher than expected (χ2 = 3385.60, p < 0.001). Pf co-infections with Pm and Po were associated with a decreased risk of fever (aOR 0.64, 95% CI 0.46–0.83; p = 0.01) and increased risks of splenomegaly (aOR 12.79, 95% CI 9.69–16.9; p < 0.001) and anaemia (aOR 2.57, 95% CI 2.09–3.15; p < 0.001), compared to single-species infections. Conclusion This study sheds light on the potential interaction between Pf and Pm and/or Po. Given the clinical significance of mixed-species infections, improved diagnostics, and case management of Pm and Po are urgently needed

    Prevalence of diarrhea and water sanitation and hygiene (WASH) associated factors among children under five years in Lira City Northern Uganda: Community based study

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    Background Children under the age of five experience a significant disease burden from diarrheal illnesses. This poses a severe public health risk as the second leading cause of infant death worldwide, after pneumonia. Lira City in Uganda is one of the developing urban areas with limited information about the diarrheal disease among children under the age of 5 years. This study aimed to determine the prevalence and assess the water, sanitation and hygiene related factors associated with diarrheal diseases among children under five years in Lira City. Methods The study was conducted among 492 care takers of children under the age of 5 years in Lira City between August 2022 and September 2022. Data was collected using an interviewer administered questionnaire and a multi-stage sampling was used to select study participants. Data was analyzed by bivariate and multivariate logistic regression using STATA version 17. P-value of < 0.05 was considered statistically significant. Results Out of 541 participants, 492 responded. The majority of the respondents, 425(86.4%) were female, 146(29.7%) had children aged 1–12 months, 192 (39%) had primary level education, and 155(31.5%) were self-employed. The prevalence of diarrhea among children under five years was 130(26.4%) and the associated factors with diarrheal disease were children between 49–60 months old (AOR = 0.12, 95% CI: 0.03–0.39, P = 0.001), cleaning the latrine more times (AOR = 0.42, 95% CI: 0.22–0.81, P = 0.010) and not treating water (AOR = 1.84, 95% CI: 1.11–3.06, P = 0.018). Conclusion There is high prevalence of diarrhea among children under 5 years of age. The study’s findings highlight the need for ongoing efforts to lower the prevalence of diarrheal illnesses among children under the age of five in Uganda’s emerging urban areas

    Kinetics and mechanistic investigation of the substitution from dinuclear Pt(II) complexes bridged by N,N’-bis(2-pyridylcarboxamide)phenylenediamines

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    The rates of substitution of the chloride ligand in dinuclear complexes, [Pt2(N,N'-bis(2-pyridylcarboxamide)-1,3-phenylenediamine)Cl4] (1), [Pt2(N,N'-bis(2-pyridylcarboxamide)-1,4-phenylenediamine)Cl4] (2), [Pt2(N,N'-bis(3-isoquinolylcarboxamide)-1,3-phenylenediamine)Cl4] (3) and [Pt2(N,N'-bis(3-isoquinolylcarboxamide)-1,4-phenylenediamine)Cl4] (4), by three bio-relevant nucleophiles, thiourea (TU), N,N-dimethylthiourea (DMTU) and N,N,N’,N’-tetramethylthiourea (TMTU), were investigated. The mononuclear analogue [Pt(N-phenylpyridine-2-carboxamide)Cl2] (5) was included to compare the results. The kinetics of the reactions were studied under pseudo first-order conditions in a methanol solution (I = 0.1 M LiCl) as a function of concentration and temperature using the stopped-flow spectrophotometer. The observed pseudo first-order rate constants for the substitution reactions of all the complexes were calculated from two well-separated steps and obey the rate law kobs (1st/2nd) = k2 (1st/2nd)[Nu]. The reactivity of the complexes decreases in the order 2 > 1 > 4 > 3 > 5. The conformational symmetry of the complexes as controlled by the phenylenediamine bridges, steric hindrance due to the bridges as well as the σ-donor capacity of the coordinated groups around the metal centers influence the reactivity of the dinuclear complexes. The low enthalpy (ΔH#) and negative intrinsic entropy (ΔS#) values support an associative mechanism of substitution. The kinetic data are supported by DFT calculations

    Knowledge, attitudes and practices towards COVID-19 among healthcare workers: A cross-sectional survey from Kiambu County, Kenya

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    The knowledge possessed by healthcare workers (HCWs), along with their attitudes and practices play a vital role in effectively managing a pandemic. This is crucial considering that HCWs are exposed to great risk at the forefront of such crises. We aimed to describe the knowledge, attitude, and practices (KAP) of HCWs during the COVID-19 pandemic in Kiambu county, Kenya. Methods A cross-sectional study using a structured questionnaire was conducted from 11th March 2021 to 12th August 2021. Bloom’s cutoff points were used to determine KAP scores (>80%: good, 60–79%: medium and <60% poor). Multivariable ordinal logistic regression analyses were conducted, calculating adjusted odds ratios (AOR) at a 95% confidence interval. Spearman’s rank correlations were used to examine the relationship between KAP scores. Results 438 HCWs participated in the study, majority of whom were female (64.5%), had obtained a diploma (59.6%) and were informed through government websites (78.6%). 43.0% had good knowledge, 17.5% good attitudes, and 68.4% good practice. 23.0% had medium knowledge, 35.6% medium attitude, 15.7% medium practice, while 34.0% had poor knowledge, 46.9% poor attitude and 15.9% poor practice. Only 68.9% of the caregivers correctly recognized the county’s COVID-19 isolation centre and only 7.9% chose the two correct documents for the entry of data for a suspected COVID-19 case. Furthermore, the general attitude towards their own personal safety and their training regarding PPEs (17.8% and 23.8% strongly agreed with the contrary) were less compelling. There was a significant positive association between obtaining information from international government sites [AOR: 1.382 (1.058–1.807); p = 0.0178)] and good knowledge. Referring to local government sites for information regarding COVID-19 produced better attitudes [AOR: 1.710 (1.194–2.465); p = 0.0036] and produced almost twice the odds of having better practice [AOR: 1.800 (1.181–2.681); p = 0.0048]. There was a significant correlation between knowledge and practice (r = -0.330, p = 2.766×10−11), and knowledge and attitude (r = -0.154, p = 6.538×10−3). Conclusion This study emphasizes the substantial impact that governing bodies have on shaping favorable KAP. As a result, it’s crucial for local government platforms to prioritize the dissemination of up-to-date information that aligns with international standards. This information should be tailored to the specific region, focusing on addressing deficiencies in healthcare practices and patient management. The identification of a significant number of HCWs lacking confidence in managing COVID-19 patients and feeling unprotected underscores a clear need for improvement in their understanding and implementation of preventive measures. This gap can be bridged by adequately equipping HCWs with locally manufactured PPEs. This aspect is crucial for pandemic preparedness, and we further advocate for the creation of a locally produced repository of medical equipment. These actions are pivotal in improving future crisis management capabilities

    Improving gonorrhoea molecular diagnostics: Genome mining-based identification of identical multi-repeat sequences (IMRS) in Neisseria gonorrhoeae

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    Curable sexually transmitted infections (STIs), such as Neisseria gonorrhoeae (N. gonorrhoeae), are a major cause of poor pregnancy outcomes. The infection is often asymptomatic in pregnant women, and a syndrome-based approach of testing leads to a missed diagnosis. Culture followed by microscopy is inadequate and time-consuming. The gold standard nucleic acid amplification tests require advanced infrastructure settings, whereas point-of-care tests are limited to immunoassays with sensitivities and specificities insufficient to accurately diagnose asymptomatic cases. This necessitates the development and validation of assays that are fit for purpose. Methods We identified new diagnostic target biomarker regions for N. gonorrhoeae using an algorithm for genome mining of identical multi-repeat sequences (IMRS). These were then developed as DNA amplification primers to design better diagnostic assays. To test the primer pair, genomic DNA was 10-fold serially diluted (100 pg/μL to 1 × 10−3 pg/μL) and used as DNA template for PCR reactions. The gold standard PCR using 16S rRNA primers was also run as a comparative test, and both assay products were resolved on 1% agarose gel. Results Our newly developed N. gonorrhoeae IMRS-PCR assay had an analytical sensitivity of 6 fg/μL representing better sensitivity than the 16S rRNA PCR assay with an analytical sensitivity of 4.3096 pg/μL. The assay was also successfully validated using clinical urethral swab samples. We further advanced this technique by developing an isothermal IMRS, which was both reliable and sensitive for detecting cultured N. gonorrhoeae isolates at a concentration of 38 ng/μL. Combining isothermal IMRS with a low-cost lateral flow assay, we were able to detect N. gonorrhoeae amplicons at a starting concentration of 100 pg/μL.This research was supported by the Royal Society, Future Leaders African Independent Researchers (FLAIR) Scheme (FLR\R1\201314) to JG

    Genetic variation of the Plasmodium falciparum circumsporozoite protein in parasite isolates from Homabay County in Kenya

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    The Plasmodium falciparum Circumsporozoite Protein (PfCSP) has been used in developing the RTS,S, and R21 malaria vaccines. However, genetic polymorphisms within Pfcsp compromise the effectiveness of the vaccine. Thus, it is essential to continuously assess the genetic diversity of Pfcsp, especially when deploying it across different geographical regions. In this study, we assessed the genetic diversity of the Pfcsp on isolates from Homabay County, a malaria-endemic region in western Kenya, and compared it against other isolates from Kenya. We extracted DNA from 27 microscopically confirmed P. falciparum positive samples and conducted Illumina sequencing to generate paired-end short reads. The sequences were then mapped to the Pf3D7 reference genome, and genetic variation was analyzed using bcftools. Additionally, we retrieved isolates from two other malaria-endemic regions in Kenya, Kisumu (n=58) and Kilifi (n=596), from MalariaGEN version 7 and compared their genetic diversity and natural selection. We also evaluated the predicted binding affinities for HLA class I and II supertype alleles for the identified haplotypes using NetMHCpan and NetMHCIIpan. Our results show that the N-terminal of PfCSP was relatively conserved with a notable mutation at A98G across all isolates. The number of NANP repeats varied across the three Kenyan sites within the central repeat region. Furthermore, the C-terminal region showed polymorphism within the Th2R and Th3R regions. Haplotype network analysis of the Kenyan isolates revealed 69 haplotypes, with the 3D7 reference being found in the most prevalent haplotype. When assessing the predicted binding affinities between supertypes in HLA class I and II with the identified haplotypes, we observed stronger predicted binding affinities to multiple haplotypes except for those containing the 3D7 reference. The results suggest the need to take into account the existing changes occurring in Pfcsp while developing malaria vaccines.The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by BK an EDCTP Fellow under EDCTP2 programme supported by the European Union grant number TMA2020CDF-3203. JG received support from the African Academy of Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    Knowledge, Perception, and Practice of Safe Medical Circumcision on HIV Infection Risk Reduction among Undergraduate Students of a Public University in Northern Uganda: A Cross-Sectional Study

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    Background. About 70% (25.6 million) of the global HIV/AIDS burden is from Sub-Saharan Africa. Safe male circumcision (SMC) is one of the measures that were adopted by the Ugandan government aimed at reducing the risk of HIV infection contraction, as recommended by the WHO. Its main goal was to maximize HIV prevention impact with voluntary medical circumcision services to all adult men and adolescent boys. The objective of our study was to assess the knowledge, perception, and practice of safe medical circumcision on HIV infection risk reduction among undergraduate students of a public university in Northern Uganda. Methods. We conducted a cross-sectional survey among 556 randomly selected Lira University undergraduate students from March 2023 to June 2023. With the use of a self-administered questionnaire, we collected data on the knowledge and perceptions of undergraduate students towards safe medical circumcision. Data were exported to Stata® 17 statistical software. Univariate, bivariate, and multivariate regression analyses were done at a statistical level of significance P value < 0.05. Results. Our 556 study participants had an age range of 21-25 years. The majority (81.29%) of the respondents knew that safe medical circumcision reduces the risk of acquiring HIV. However, the perception is that close to 3 in 4 (74.46%) of the students were unsure if they would opt for safe medical circumcision as risk reduction measure against HIV. The practice of safe medical circumcision was 64.8% among the study participants. Conclusions. More than three in four of the undergraduate students have knowledge on safe medical circumcision as risk reduction measure for HIV infection. And close to 3 in 4 (74.46%) of the student’s perception were unsure if they would opt for safe medical circumcision as risk reduction measure against HIV. The practice of safe medical circumcision was 64.8% among the study participants. Therefore, in an effort to increase SMC’s adoption for HIV/AIDS prevention, the Ministry of Health of Uganda and related stakeholders in health should work hand in hand with university study bodies in order to optimize SMC uptake among university students

    Identification of conserved cross-species B-cell linear epitopes in human malaria: a subtractive proteomics and immuno-informatics approach targeting merozoite stage proteins

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    Human malaria, caused by five Plasmodium species (P. falciparum, P. vivax, P. malariae, P. ovale, and P. knowlesi), remains a significant global health burden. While most interventions target P. falciparum, the species associated with high mortality rates and severe clinical symptoms, non-falciparum species exhibit different transmission dynamics, remain hugely neglected, and pose a significant challenge to malaria elimination efforts. Recent studies have reported the presence of antigens associated with cross-protective immunity, which can potentially disrupt the transmission of various Plasmodium species. With the sequencing of the Plasmodium genome and the development of immunoinformatic tools, in this study, we sought to exploit the evolutionary history of Plasmodium species to identify conserved cross-species B-cell linear epitopes in merozoite proteins. We retrieved Plasmodium proteomes associated with human malaria and applied a subtractive proteomics approach focusing on merozoite stage proteins. Bepipred 2.0 and Epidope were used to predict B-cell linear epitopes using P. falciparum as the reference species. The predictions were further compared against human and non-falciparum databases and their antigenicity, toxicity, and allergenicity assessed. Subsequently, epitope conservation was carried out using locally sequenced P. falciparum isolates from a malaria-endemic region in western Kenya (n=27) and Kenyan isolates from MalariaGEN version 6 (n=131). Finally, physiochemical characteristics and tertiary structure of the B-cell linear epitopes were determined. The analysis revealed eight epitopes that showed high similarity (70-100%) between falciparum and non-falciparum species. These epitopes were highly conserved when assessed across local isolates and those from the MalariaGEN database and showed desirable physiochemical properties. Our results show the presence of conserved cross-species B-cell linear epitopes that could aid in targeting multiple Plasmodium species. Nevertheless, validating their efficacy in-vitro and in-vivo experimentally is essential

    Combating antibiotic resistance using guidelines and enhanced stewardship in Kenya: a protocol for an implementation science approach

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    Antimicrobial resistance (AMR) is a growing problem globally especially in Sub-Saharan Africa including Kenya. Without any intervention, lower/middle-income countries (LMICs) will be most affected due to already higher AMR levels compared with higher income countries and due to the far higher burden of diseases in the LMICs. Studies have consistently shown that inappropriate use of antimicrobials is the major driver of AMR. To address this challenge, hospitals are now implementing antibiotic stewardship programmes (ASPs), which have been shown to achieve reduced antibiotic usage, to decrease the prevalence of resistance and lead to significant economic benefits. However, the implementation of the guideline is highly dependent on the settings in which they are rolled out. This study, employing an implementation science approach, aims to address the knowledge gap in this area and provide critical data as well as practical experiences when using antibiotic guidelines and stewardship programmes in the public health sector. This will provide evidence of ASP performance and potentially contribute to the county, national and regional policies on antibiotics use

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