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Placental malaria is associated with a TLR–Endothelin-3–oxidative damage response in 1 human placenta tissues
No full textPlacental malaria, which is mainly caused by the sequestration of Plasmodium falciparum-infected erythrocytes in the placenta, is an important driver of poor pregnancy outcomes, including fetal growth restriction, preterm birth, and stillbirth. However, the mechanisms underlying its adverse outcomes are unclear. Mouse models have previously shown that placental malaria (PM) triggers a proinflammatory response in the placenta, which is accompanied by a fetal Toll-like receptor (TLR)4-mediated innate immune response associated with improved fetal outcomes. Here, we used hematoxylin and eosin staining to identify PM-positive and negative samples in our biobank of placentas donated by women living in a malaria-endemic region of Kenya and assessed the impact of PM on the expression of TLRs, Endothelins, and oxidative damage. RT-qPCR analysis revealed that PM was associated with an upregulation of TLR4, TLR7, and Endothelin-3. Moreover, immunohistochemistry showed that PM was associated with elevated expression levels of the oxidative DNA damage marker, 8-hydroxy-2’-deoxyguanosine, while RT-qPCR revealed that this was accompanied by an upregulation of p21, an inhibitor of cell cycle progression and marker of cellular response to DNA damage. These findings allude to a novel mechanism of PM pathogenesis driven by a TLR–Endothelin-3–oxidative DNA damage signaling axis
Qualitative study on stigma as a barrier to emergency contraceptive pill use among university students in the Lango subregion, Uganda
Full text linkObjective The aim of the current study was twofold: to understand the nature and extent of stigma and to learn the reasons behind the decision not to use emergency contraceptive pills among university students in the Lango subregion of Uganda.
Design An exploratory qualitative study design.
Setting The study was carried out among university students in Lango subregion of Uganda.
Participants 40 female university students across four universities.
Main outcome measures Stigma.
Results Participants (n=40) aged 19–26 exhibited generally positive attitudes towards emergency contraceptive pills, recognising them as empowering and essential. Stigma, however, emerged as a substantial barrier manifested in societal judgements and negative perceptions. Themes included the positive attitude towards emergency contraceptive pills, perceptions of peers and the general public, and perceptions of health service providers.
Conclusion Stigma significantly impedes emergency contraceptive pill use among university students in the Lango subregion, Uganda. Positive attitudes towards the pills contrast with societal judgements and provider stigmatisation. Tailored interventions addressing knowledge gaps, societal perceptions and healthcare system challenges are crucial for improving emergency contraceptive pill acceptability and utilisation among university students
Unraveling the “indirect effects” of interventions against malaria endemicity: A systematic scoping review
No full textThere 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
An Analysis of Post-Traumatic Stress Disorder and Quality of Life Among Adults Living with HIV in Western Uganda
No full textBackground: 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
Multi-repeat sequences identification using genome mining techniques for developing highly sensitive molecular diagnostic assay for the detection of Chlamydia trachomatis
No full textChlamydia trachomatis (C. trachomatis) is a common sexually transmitted infection (STI). In 2019, the World Health Organization reported about 131 million infections. The majority of infected patients are asymptomatic with cases remaining undetected. It is likely that missed C. trachomatis infections contribute to preventable adverse health outcomes in women and children. Consequently, there is an urgent need of developing efficient diagnostic methods. In this study, genome-mining approaches to identify identical multi-repeat sequences (IMRS) distributed throughout the C. trachomatis genome were used to design a primer pair that would target regions in the genome. Genomic DNA was 10-fold serially diluted (100pg/μL to 1×10-3pg/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 products were resolved on agarose gel. The novel assay, C. trachomatis IMRS-PCR, had an analytical sensitivity of 4.31 pg/μL, representing better sensitivity compared with 16S rRNA PCR (9.5 fg/μL). Our experimental data demonstrate the successful development of lateral flow and isothermal assays for detecting C. trachomatis DNA with potential use in field settings. There is a potential to implement this concept in miniaturized, isothermal, microfluidic platforms, and laboratory-on-a-chip diagnostic devices for reliable point-of-care testing
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
No full textBackground: 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 (2,000 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.This work is supported by Japan International Cooperation Agency (JICA), Japan Agency for Medical Research and Development (AMED) under the Science and Technology Research Partnership for Sustainable Development Goals (SATREPS) program, and JSPS KAKENHI (Grant Number JP21H051080)
The effect of the chelate ligand on the rate of chloride substitution from Pt(II) complexes with picolyl and isoquinolinylcarboxamide moieties on the non-leaving ligand
No full textSubstitution reactions of four Pt(II) complexes, namely; N-(2-picolyl)picolinamide-platinum(II) chloride (Pt3), N-(8-quinolyl)pyridine-2-carboxamide platinum(II) chloride (Pt4), N-(8-quinolyl)-3-isoquinolinecarboxamide platinum(II) chloride (Pt5) and N-(8-quinolinyl)-1-isoquinolinecarboxamide platinum(II) chloride (Pt6), were studied with biorelevant nucleophiles, viz. thiourea (TU), N,N′-dimethylthiourea (DMTU) and N,N,N′,N′-tetramethylthiourea (TMTU) under pseudo first order conditions as a function of concentration and temperature using the stopped flow spectrophotometer. The observed pseudo first order rate constants for the substitution reactions obey the rate law kobs = k2[Nu]. The reactivity of the studied complexes depends on strength of π-backbonding of the attached ligands, which is enhanced by the strong electron withdrawing nature of the carboxamide group on the non-leaving ligands of Pt(II) complexes. Quinoline moieties of Pt5 and Pt6 lie out-of-the square plane, resulting in enhanced reactivity due to the aided entrapment of the nucleophile by the non-planar groups of the ligand. Negative activation entropies and positive enthalpies of activation support an associative mode of activation
Improving gonorrhoea molecular diagnostics: Genome mining-based identification of identical multi-repeat sequences (IMRS) in Neisseria gonorrhoeae
No full textBackground
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
Evaluation of the protective efficacy of Olyset®Plus ceiling nets for reduction of malaria incidence in 2 children in Homa Bay County, Kenya: a cluster-randomized controlled study protocol
No full textIntroduction 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
Development of a rapid and highly sensitive nucleic acid-based diagnostic test for schistosomes, leveraging on identical multi-repeat sequences
No full textDepartment of Molecular Biology and Biotechnology, Pan African University Institute for Basic Sciences, Technology and Innovation (PAUSTI), Nairobi, Kenya
Department of Biology, College of Natural and Mathematical Sciences, University of Dodoma, Dodoma, Tanzania
Center for Research in Infectious Diseases, College of Graduate Studies and Research, Mount Kenya University, Thika, Kenya
Division of Research and Development, Jigsaw Bio Solutions Private Limited, Bangalore, India
Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya
Department of Medical Microbiology and Parasitology, Kenyatta University, Nairobi, Kenya
SACIDS Africa Center of Excellence for Infectious Diseases, Sokoine University of Agriculture, Morogoro, Tanzania
Department of Biochemistry, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya
Department of Computer Science and Applications, KL University, Andhra Pradesh, Guntur, India
Department of Tropical and Infectious Diseases, Institute of Primate Research, Nairobi, Keny