(Pyrazolyl)pyridine ruthenium(III) complexes: Synthesis, kinetics of substitution reactions with thiourea and biological studies

Reactions of 2-bromo-6-(3,5-dimethyl-1H-pyrazol-1-yl)pyridine (L1), 2,6-di (1H-pyrazol-1-yl) pyridine (L2) and 2,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)pyridine (L3) with RuCl3·3H2O led to the formation of their respective metal complexes [RuCl3(L1)] (1), [RuCl3(L2)] (2) and [RuCl3(L3)] (3). Solid state structure of complex 3 established the formation of a six-coordinate mononuclear compound in which L3 is tridentately bound. The order of reactivity of the studied complexes with thiourea (TU) nucleophile is in the form 1 > 2 > 3, in line with density functional theory (DFT) studies. The complexes displayed minimal cytotoxic activity against the HeLa cell line, consistent with molecular docking experiments which showed weaker DNA binding affinities

Evaluation of the protective efficacy of OlysetPlus ceiling nets for reduction of malaria incidence in children in Homa Bay County, Kenya: a cluster-randomized controlled study protocol

Introduction Malaria is still a major health problem in sub-Saharan Africa, where 98% of global malaria mortality occurs. In addition, the spread of Plasmodium falciparum with partial artemisinin resistance in East Africa and beyond is a great concern. The establishment of more effective vector control, in addition to the current long-lasting insecticide-treated net (LLIN) distribution program, is an urgent task in these areas. One novel vector control candidate is the Olyset®Plus ceiling nets which can overcome the problems of variations in net use behaviors and metabolic resistance to insecticide in vectors. Our preliminary study suggests the protective efficacy and high acceptability of this tool. With this proposed second trial, we aim to evaluate the impact of this tool in a different eco-epidemiological setting in the lake endemic region of Kenya. Methods A cluster randomized controlled trial is designed to evaluate the impact of Olyset®Plus ceiling nets in Ndhiwa Sub-County, Homa Bay County, Kenya. A total of 44 clusters will be randomly assigned in a 1:1 ratio to the intervention group (Olyset®Plus ceiling nets) and the control group. The assignment will be accomplished through covariate-constrained randomization of clusters. For the primary outcome of clinical malaria incidence, 38 children from each cluster will be enrolled in a cohort and followed for 18 months. We will also evaluate the effects of the intervention on entomological indicators as well as its acceptance by communities and cost-effectiveness. Ethics and dissemination Ethics approval was provided by the Mount Kenya University Institutional Scientific Ethics Review Committee. Study results will be shared with study participants and communities, the Homa Bay County Government and the Kenya National Malaria Control Programme. Results will also be disseminated through publications, conferences and workshops to help the development of novel malaria control strategies in other malaria-endemic countries.YKK and MK were financially supported by the Japan Society for the Promotion of Science. AK and JG received support from JICA/AMED joint research project (SATREPS) (Grant no. 20JM0110020H0002), Hitachi Fund Support for Research Related to Infectious Diseases, and Sumitomo Chemical Corporation. The funding bodies play no role in the study design, data collection, analysis, interpretation, and publication

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

Background 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. Conclusion Therefore, there is a potential to implement this concept within miniaturized, isothermal, microfluidic platforms, and laboratory-on-a-chip diagnostic devices for highly reliable point-of-care testing

Unraveling the “indirect effects” of interventions against malaria endemicity: A systematic scoping review

There is an urgent need to maximize the effectiveness of existing malaria interventions and optimize the deployment of novel countermeasures. When assessing the effects of interventions against malaria, it is imperative to consider the interdependence of people and the resulting indirect effects, without which the impact on health outcomes and their cost-effectiveness may be miscalculated. Here, we conducted a scoping review of existing literature on the indirect effects of malaria interventions. We observed a recent increase in both the number of reports and the variety of terms used to denote indirect effects. We further classified eight categories of comparative analysis to identify the indirect effects, proposed common terms for the indirect effects, and highlighted the potential benefits of mathematical models in estimating indirect effects. Improving the study design and reporting the indirect effects of malaria interventions will lead to better informed decisions by policymakers

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

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

Metatranscriptomic analysis of wastewater sites reveals a high abundance of antimicrobial resistance genes from hospital wastewater

Objective This study analyzed the metatranscriptome of wastewater samples from different sites with a focus of identifying antibiotic resistance genes and the bacterial community. Methods Twenty-four wastewater samples were collected from a hospital, university sewer, and the influent and effluent of a wastewater treatment plant (WWTP). The metatranscriptome was sequenced to identify antimicrobial resistance genes (ARGs), mobile genetic elements, and bacterial community composition. Results Metatranscriptome analysis revealed varying abundances of ARG transcripts across different sites, with 84, 27, 14, and 9 ARG transcripts identified in wastewater collected from the hospital, university, influent, and effluent of a WWTP, respectively. Notably, hospital wastewater contained clinically relevant beta-lactam ARGs, including bla-NDM-1 and several blaOXA transcripts. Four core ARGs, against sulfonamides sul1 and sul2 and aminoglycosides aph(6)-ld and aph(’3’)-lb were also identified. The predominant bacterial community comprised of Gammaproteobacteria, with priority pathogens like Neisseria gonorrhea and Helicobacter pylori present in hospital wastewater and WWTP influent. Conclusion These findings provide insights into the wastewater resistome and how meta-transcriptomic data can be utilized for the surveillance of antibiotic resistance. Overall, our study highlights the utility of wastewater surveillance in understanding and addressing the dissemination of antibiotic resistance and emphasizes the crucial role of proper wastewater management in protecting public and environmental health.This study was funded by the Kenya National Research Fund NRF/MKU/2017/007 to J

Access to family planning services and associated factors among young people in Lira city northern Uganda

Background Access to family planning services among young people is crucial for reproductive health. This study explores the access and associated factors among young people in Lira City, Northern Uganda. Methods and materials A mixed-methods study was conducted in March to April 2022. Quantitative data were collected using a structured questionnaire from 553 participants aged 15–24 years. Qualitative data were obtained through in-depth interviews and focus group discussions. Data analysis included univariate, bivariate, and multivariate analyses for quantitative data, while interpretative phenomenological analysis was used for qualitative data. Results Overall, 31.7% of the respondents had a good perceived access to family planning services, with 64.6% reporting perceived availability of FP methods. Challenges included lack of privacy (57.7%), fear of mistreatment (77.2%), and decision-making difficulties (66.2%). Among females, good perceived access to FP services was less likely among urban residents (AOR: 0.22, 95% CI: 0.09–0.53), Christian respondents (AOR: 0.51, 95% CI: 0.01–0.36), Muslim respondents (AOR: 0.07, 95% CI: 0.01–0.55) and respondents with poor attitude to FP services (AOR: 0.39, 95% CI: 0.24–0.64), but more likely among respondents with a sexual a partner (AOR: 4.48, 95% CI: 2.60–7.75). Among males, good perceived access to FP services was less likely among respondents living with parents (AOR: 0.19, 95% CI: 0.05–0.67) but more likely among respondents with good knowledge of FP services (AOR: 2.28, 95% CI: 1.02–5.32). Qualitative findings showed that three themes emerged; knowledge of family planning methods, beliefs about youth contraception and, friendliness of family planning services. Conclusion The study revealed a substantial gap in perceived access to family planning services among young people in Lira City. Barriers include privacy concerns, fear of mistreatment, and decision-making difficulties. Tailored interventions addressing urban access, religious beliefs for females, and knowledge enhancement for males are essential. Positive aspects like diverse FP methods and physical accessibility provide a foundation for targeted interventions. Youth-friendly services, comprehensive sexual education, and further research are emphasized for a nuanced understanding and effective interventions in Northern Uganda

The Lived Experiences of Individuals and Coping Strategies in the Context of Internet Gaming Disorder: A Qualitative Study Within Higher Education Setting in Uganda

Background: Internet Gaming Disorder (IGD), recognized as a mental disorder in both the Diagnostic and Statistical Manual (DSM-5) and International Classification of Diseases (ICD-11), poses significant threats to physical, social, and mental well-being. This study aims to delve into the experiences of individuals grappling with IGD. Methods and Materials: The study employed an interpretive phenomenology, conducting interviews with 10 graduate students at Makerere University. Participants were purposefully sampled until data saturation was achieved during interviews, which took place between May and July 2023. An interview guide facilitated data collection (Supplementary File 1), and thematic analysis was manually applied for data interpretation, utilizing intuition and imaginative approaches. Results: The findings revealed that the majority of participants started gaming during childhood, starting with offline games. Exposure to gadgets and games, idle time, and stress emerged as key triggers for IGD. Participants reported experiencing sleep deficits, deteriorating interpersonal relationships, declining job performance, unhealthy eating habits, academic challenges, and wastage of money and time. The study also identified strategies employed by participants to mitigate their gaming behaviors, such as refraining from purchasing data, seeking support from friends, and uninstalling the game app, although relapses were common. Conclusion: The study highlights a global pattern of early initiation into gaming, emphasizing the need for early intervention and preventive measures. Factors such as easy accessibility and affordability of gaming platforms, idleness, and stress play significant roles in motivating internet gaming, contributing to a higher prevalence among the studied population. The research underscores the adverse effects of IGD on students, affecting academic performance, interpersonal relationships, and job performance. Notably, participants demonstrate agency in addressing IGD through practical coping strategies, including controlling data access, seeking social support, and uninstalling games. These coping mechanisms provide valuable insights into the complex nature of addressing IGD and form a basis for developing targeted interventions and support systems within the higher education setting in Uganda

An Analysis of Post-Traumatic Stress Disorder and Quality of Life Among Adults Living with HIV in Western Uganda

Background: HIV/AIDS remains a significant global public health issue, profoundly impacting infected individuals. Living with HIV involves complex mental health dynamics, with post-traumatic stress disorder (PTSD) being a prevalent challenge. This study aims to examine the correlation between PTSD and quality of life among HIV-positive individuals in western Uganda. Material and Methods: Conducted between May and July 2023, this facility-based cross-sectional study surveyed 439 participants from four HIV clinics in southwestern Uganda. Data were collected through interviewer-administered questionnaires, analyzed using descriptive statistics, simple linear regression, and multiple linear regression (p< 0.05). Results: Respondents had a mean age of 40.6 years, with 68.3% female, 54.9% married, and 55.1% lacking formal education. The reported PTSD prevalence among HIV-positive individuals was 33.7%, significantly correlating with reduced overall quality of life (β = − 4.52; p< 0.001). The social quality of life had the highest mean score of 14.24 (± 3.45) while the environmental quality of life had the lowest mean score 11.89 (± 2.68). Conclusion: Our study reveals a concerning prevalence of PTSD, affecting 1 in 3 individuals, emphasizing the pressing need for comprehensive mental health support within HIV care settings. We observed a significant negative impact of PTSD on overall quality of life, particularly in physical and social aspects. Integrating mental health screening into routine HIV care is crucial, using validated tools like the PSTD Checklist Civilian Version, alongside training for healthcare providers to recognize PTSD symptoms in the context of HIV diagnosis and treatment

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

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