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

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

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

Background: 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)

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

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

Placental malaria is associated with a TLR–Endothelin-3–oxidative damage response in 1 human placenta tissues

Placental 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

Objective 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

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

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.The author(s) declare financial support was received for the research, authorship, and/or publication of this article. BK is an EDCTP fellow under the EDCTP2 program supported by the European Union grant number TMA2020CDF-3203-EndPAMAL. JG is supported by the African Academy of Sciences and Royal Society FLAIR grant number FLR\R1\201314

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

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)

Predictors of birth weight in pregnant women with malaria: a prospective cohort facility-based study in Webuye-Kenya

In sub-Saharan Africa, malaria, which remains a major public health burden, has a prevalence of 9 to 28% and malaria in pregnancy is associated with severe adverse outcomes for the mother and her baby. Here, we sought to determine the predictors of birth weight in a cohort of 140 women with malaria in pregnancy, who were recruited at the Webuye County hospital in Western Kenya. All study participants underwent malaria diagnosis through microscopic examination of blood smear samples and were grouped into the malaria-positive and malaria-negative groups. Both groups were followed up beginning at the first antenatal visit (March 2022) until delivery (December 2022) and various data, including demographic, parity, gravidity, socioeconomic, maternal and fetal outcomes were collected. Data analyses were done using SPSS version 27. Chi-square and Fisher’s Exact tests were used for bivariate and relative risk analyses at a p-value of ≤0.05 (95%) confidence level. Most of the participants were aged 18–25 years, were primigravidas and married, had secondary school-level education, earned 20–30 thousand Kenya shillings, resided in rural areas, and were in the second trimester. There were 6 (4.6%) cases of low birth weight, 3 (4.5%) in the malaria-negative group and 3 (4.7%) in the malaria-positive group. During pregnancy, 41 (31.5%) were anaemic, 5 (3.8%) were HIV-positive, 5 (3.8%) had preeclampsia, and 2 (1.5%) had gestational diabetes. Our analyses show that confounding factors like anaemia, HIV, pre-eclampsia and gestational diabetes did not influence birthweight (p ≥ 0.923). The malaria-positive and malaria-negative groups did not differ significantly with regard to the low birth weight (relative risk: 0.999, 95% confidence interval: 0.926–1.077). Marital status, gestational age, and area of residence were associated with malaria p ≤ 0.001, ≤ 0.001 and 0.028 respectively. In both groups, 124 of the 140 deliveries had normal birth weights and of these 63 (95.4%, n = 70) were in the malaria-negative group, whereas 61 (95.3%, n = 70) belonged to the malaria-positive group

Autoantibodies inhibit Plasmodium falciparum growth and are associated with protection from clinical malaria

Many infections, including malaria, are associated with an increase in autoantibodies (AAbs). Prior studies have reported an association between genetic markers of susceptibility to autoimmune disease and resistance to malaria, but the underlying mechanisms are unclear. Here, we performed a longitudinal study of children and adults (n = 602) in Mali and found that high levels of plasma AAbs before the malaria season independently predicted a reduced risk of clinical malaria in children during the ensuing malaria season. Baseline AAb seroprevalence increased with age and asymptomatic Plasmodium falciparum infection. We found that AAbs purified from the plasma of protected individuals inhibit the growth of blood-stage parasites and bind P. falciparum proteins that mediate parasite invasion. Protected individuals had higher plasma immunoglobulin G (IgG) reactivity against 33 of the 123 antigens assessed in an autoantigen microarray. This study provides evidence in support of the hypothesis that a propensity toward autoimmunity offers a survival advantage against malaria

Development of a rapid and highly sensitive nucleic acid-based diagnostic test for schistosomes, leveraging on identical multi-repeat sequences

Department 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