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Malaria remains a key health and economic problem, particularly in sub-Saharan Africa. The emergence of artemisinin drug resistance (ART-R) parasite strains poses a serious threat to the control and elimination of this scourge. This is because artemisinin-based combination therapies (ACTs) remain the first-line treatment in the majority of malaria-endemic regions in Sub-Saharan Africa. Certain single-nucleotide polymorphisms in the propeller domains of Plasmodium falciparum Kelch 13 protein (K13) have been associated with delayed parasite clearance in vivo and in vitro. These mutations serve as vital molecular markers for tracking the emergence and dispersion of resistance. Recently, there have been increasing reports of the emergence and spread of P. falciparum ART-R parasites in the Eastern Africa region. This necessitates continued surveillance to best inform mitigation efforts. This study investigated the presence of all reported mutations of K13 propeller domains in the parasite population in Busia County, Kenya, a known malaria-endemic region. Two hundred twenty-six participants with microscopically confirmed uncomplicated malaria were recruited for this study. They were treated with artemether-lumefantrine under observation for the first dose, and microscopic examination was repeated 1 day later after ensuring the participants had taken the second and third doses. P. falciparum DNA from all samples underwent targeted amplification of the K13 gene using a semi-nested PCR approach, followed by Sanger sequencing. The recently validated ART-R K13 mutation C469Y was identified in three samples. These three samples were among 63 samples with a low reduction in parasitemia on day 1, suggesting day 1 parasitemia reduction rate is a useful parameter to enrich the ART-R parasites for further analysis. Our findings highlight the need for continuous surveillance of ART-R in western Kenya and the region to determine the spread of ART-R and inform containment., (© 2024. The Author(s).)

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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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 January-February 2012 and September-October 2018. In each survey, a minimum of 100 children aged 3 to 15 years were randomly chosen from a school in Ungoye village on the mainland and as well as from each school selected in every catchment area on Mfangano island. 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 (χ 2 )., Results: The Plasmodium prevalence was 25.9% (2521/9724) by microscopy and 51.1% (4969/9724) by PCR. Among all infections detected by PCR, Pf, P. malariae (Pm), and P. ovale (Po) mono-infections were 58.6%, 3.1%, and 1.8%, 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 being significantly higher than expected (χ 2  = 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., (© 2024. The Author(s).)

Cytochrome P450 3A4 (CYP3A4) enzyme is involved in the metabolism of about 30 % of clinically used drugs, including the antimalarials artemether and lumefantrine. CYP3A4 polymorphisms yield enzymatic variants that contribute to inter-individual variation in drug metabolism. Here, we examined CYP3A4 polymorphisms in populations from malaria-endemic islands in Lake Victoria, Kenya, and Vanuatu, to expand on the limited data sets. We used archived dried blood spots collected from 142 Kenyan and 263 ni-Vanuatu adults during cross-sectional malaria surveys in 2013 and 2005-13, respectively, to detect CYP3A4 variation by polymerase chain reaction (PCR) and sequencing. In Kenya, we identified 14 CYP3A4 single nucleotide polymorphisms (SNPs), including the 4713G (CYP3A4∗1B; allele frequency 83.9 %) and 19382A (CYP3A4∗15; 0.7 %) variants that were previously linked to altered metabolism of antimalarials. In Vanuatu, we detected 15 SNPs, including the 4713A (CYP3A4∗1A; 88.6 %) and 25183C (CYP3A4∗18; 0.6 %) variants. Additionally, we detected a rare and novel SNP C4614T (0.8 %) in the 5' untranslated region. A higher proportion of CYP3A4 genetic variance was found among ni-Vanuatu populations (16 %) than among Lake Victoria Kenyan populations (8 %). Our work augments the scarce data sets and contributes to improved precision medicine approaches, particularly to anti-malarial chemotherapy, in East African and Pacific Islander populations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)

Overview: The roadmap adopted by the World Health Organization (WHO) for eliminating neglected tropical diseases aims to eliminate schistosomiasis, as a public health concern, by 2030. While progress has been made towards reducing schistosomiasis morbidity control in several sub-Saharan African countries, there is still more that needs to be done. Proper surveillance using accurate diagnostics with acceptable sensitivity and specificity is essential for evaluating the success of all efforts against schistosomiasis. Microscopy, despite its low sensitivity, remains the gold standard approach for diagnosing the disease. Although many efforts have been made to develop new diagnostics based on circulating parasite proteins, genetic markers, schistosome egg morphology, and their paramagnetic properties, none has been robust enough to replace microscopy. This review highlights common diagnostic approaches for detecting schistosomiasis in field and clinical settings, major challenges, and provides new and novel opportunities and diagnosis pathways that will be critical in supporting elimination of schistosomiasis., Methods: We searched for relevant and reliable published literature from PubMed, Scopus, google scholar, and Web of science. The search strategies were primarily determined by subtopic, and hence the following words were used (schistosom*, diagnosis, Kato-Katz, antibody test, circulating antigen, POC-CCA, UCP-LF-CAA, molecular diagnostics, nucleic acid amplification test, microfluidics, lab-on a disk, lab-on chip, recombinase polymerase amplification (RPA), LAMP, portable sequencer, nanobody test, identical multi-repeat sequences, diagnostic TPPs, REASSURED, extraction free), and Boolean operators AND and/OR were used to refine the searching capacity. Due to the global public health nature of schistosomiasis, we also searched for reliable documents, reports, and research papers published by international health organizations, World Health Organization (WHO), and Center for Disease control and Elimination., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Ally et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Regular monitoring of bacterial susceptibility to antibiotics in clinical settings is key for ascertaining the current trends as well as re-establish empirical therapy. This study aimed to determine bacterial contaminants and their antimicrobial susceptibility patterns from medical equipment, inanimate surfaces and clinical samples obtained from Thika Level V Hospital (TLVH), Thika, in Central Kenya. Three hundred and five samples were collected between the period of March 2021 to November 2021 and comprised urine, pus swabs, catheter swabs, stool, and environmental samples. Bacterial identification and antimicrobial susceptibility were performed using VITEK 2 and disc diffusion respectively. We observed that Coagulase-negative Staphylococci (28 /160, 17.5%) were the most commonly isolated species from clinical samples followed by E. coli (22 /160 13.8%) and S. aureus (22/160, 13.8%). The bed rails were the mostly contaminated surface with S. aureus accounting for 14.2% (6/42). Among the clinical samples, pus swabs yielded the highest number of pathogens was pus (92/160). Trauma patients had the highest proportion of isolates (67/160, 41.8%). High level of antimicrobial resistance to key antimicrobials, particularly among Enterobacterales was observed. Extended Spectrum Beta Lactamase (ESBL) phenotype was noted in 65.9% (29/44) of enteric isolates. While further ESBL genetic confirmatory studies are needed, this study highlights the urgent need for actions that mitigate the spread of antibiotic-resistant bacteria., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kimani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© 2024. The Author(s).)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflict of interest., (Copyright © 2024 Musundi, Gitaka and Kanoi.)