Impact of COVID-19 on the Utilization of Maternal and Child Health Services at a Regional Referral Hospital in Kenya.

Background and Objective: Pandemics, like COVID-19, disrupt healthcare, potentially reversing progress in various disease areas. The impact on maternal and child health (MCH) services in Kenya during the pandemic is yet to be determined. Recognizing this impact is crucial for formulating policies and programs that minimize disruptions in reproductive health services during future health crises. The purpose of this study was to determine the effect of COVID-19 on the uptake of MCH services at Thika Level V Hospital, a regional referral hospital in Kenya. Methods: In this cross-sectional mixed methods study, we reviewed antenatal clinic (ANC), MCH, and family planning (FP) registers for data on the uptake of the various services during the COVID-19 pandemic (July to October 2020) compared to a year before the COVID-19 pandemic (July to October 2019). MCH clients (N = 60) and healthcare workers (N = 19) were interviewed about the impact of the pandemic on MCH services at the hospital. Differences in clinic attendance before and during the pandemic were compared using the student t-test. Thematic analysis was conducted on the interview responses. Results: The number of MCH/FP clients dropped from 12,915 pre-pandemic to 7,429 during the pandemic. Significant differences were noted in ANC revisits (p = 0.026) and those completing the World Health Organization recommended minimum of four ANC visits (p<0.001) during the COVID-19 pandemic. The number of revisits at the child welfare clinic was also significantly lower (p = 0.004) during the COVID-19 lockdown period. MCH clients stated that the decline in the uptake of MCH services was attributable to the fear of contracting disease, financial difficulties, and strain on the healthcare workforce. Conclusion and Global Health Implications: This study found a decline in access to MCH/FP services during the COVID-19 crisis with the potential to reverse gains made in securing the safety of the pregnant mother and unborn baby.

Emerging Drug Targets for Antimalarial Drug Discovery: Validation and Insights into Molecular Mechanisms of Function.

Approximately 619,000 malaria deaths were reported in 2021, and resistance to recommended drugs, including artemisinin-combination therapies (ACTs), threatens malaria control. Treatment failure with ACTs has been found to be as high as 93% in northeastern Thailand, and parasite mutations responsible for artemisinin resistance have already been reported in some African countries. Therefore, there is an urgent need to identify alternative treatments with novel targets. In this Perspective, we discuss some promising antimalarial drug targets, including enzymes involved in proteolysis, DNA and RNA metabolism, protein synthesis, and isoprenoid metabolism. Other targets discussed are transporters, Plasmodium falciparum acetyl-coenzyme A synthetase, N-myristoyltransferase, and the cyclic guanosine monophosphate-dependent protein kinase G. We have outlined mechanistic details, where these are understood, underpinning the biological roles and hence druggability of such targets. We believe that having a clear understanding of the underlying chemical interactions is valuable to medicinal chemists in their quest to design appropriate inhibitors.

Student's perspectives, satisfaction and experiences with online and classroom learning during the COVID-19 pandemic: Findings and implications on blended learning.

Objectives: The coronavirus disease 2019 (COVID-19) pandemic disrupted classroom-based learning, necessitating the adoption of online learning in most universities. However, there has been a lack of information on university students' perspectives regarding online learning during the COVID-19 pandemic. This study assessed the perspectives, satisfaction and experiences with online and classroom learning among human health students at the University of Zambia. Methods: This cross-sectional study was conducted among 737 students at the University of Zambia from October 2022 to April 2023. Data were analysed using Stata version 16.1. Results: Of the 737 participants, 51.6% were female and 56.5% agreed that blended learning should continue even after the COVID-19 pandemic. However, 78.4% of the students believed that group discussions were more suitable in the classroom than online learning. Most students (67.1%) disagreed that they preferred online learning to classroom learning. Furthermore, 77.6% of the students disagreed that online learning gave more satisfaction than classroom learning. Conclusions: This study found that most students recommended the continuation of blended learning after the pandemic. However, they believed that follow-up tutorials and assessments were better undertaken in physical classrooms than online learning. These findings are important in sensitising stakeholders in the education sector and governments to consider blended learning as a teaching strategy in the future. There is a need to develop and implement curricula that offer blended learning to students as well as ensure the students have the necessary facilities and equipment to support such learning.

Medicinal Chemistry and Target Identification of Synthetic Clinical and Advanced Preclinical Antimalarial Candidates (2000 - 2022).

BACKGROUND: The downward trend in malaria cases and deaths is steadily reversed - 627,000 deaths in 2020 compared to 405,000 deaths in 2018. Drug resistance has compromised the effectiveness of currently available treatment options, with some reports documenting molecular markers of resistance to artemisinins in African countries in addition to the Greater Mekong subregion, which was initially associated with this kind of resistance. Therefore, the development of novel drugs is crucial to replenishing the antimalarial drug arsenal toward malaria eradication. In this review, we summarize the progress made in antimalarial drug discovery in the period 2000 - 2022, focusing on drug candidates which have made it to advanced preclinical trials (drugs tested in rodent species and at least one higher species such as dog or monkey) and beyond. METHODS: We searched Google Scholar and selected studies meeting these defined criteria. We highlight the medicinal chemistry optimization of these compounds; the preclinical/clinical evaluation and the mechanisms of action. RESULTS AND CONCLUSION: Although the pipeline seems promising, the prospect of having an antimalarial medicine that meets the current target product profiles (TPPs) towards the malaria eradication agenda is far from reality. Some of the key TPP attributes required include multistage activity, resistance- proof; ability to achieve a single dose cure and safety across a wide range of patient populations. Clinical trials are ongoing for some promising molecules, inspiring optimism toward identifying better drugs that meet these defined TPPs. Until then, concerted research efforts should continue to be mounted to populate the antimalarial drug discovery and development pipeline.

Knowledge and practices toward COVID-19 among healthcare students: A cross-sectional study at the University of Zambia.

Background: The COVID-19 pandemic led to the disruption of physical classes for university students globally, as large gatherings fuelled the transmission of the virus. In the efforts to mitigate its transmission and return to normality, prevention measures, including vaccination, have been encouraged. Therefore, it is critical to understand the knowledge and practices of students regarding COVID-19. This study assessed the knowledge and practices toward COVID-19 among healthcare students at the University of Zambia. Materials and methods: This questionnaire-based cross-sectional study was carried out from August 2021 to October 2021 among 478 healthcare students (pharmacy, physiotherapy, nursing, biomedical, medicine, and radiography). We used a previously validated questionnaire to measure knowledge and practice. The predictors of knowledge and practices were assessed using logistic regression with robust estimation of standard errors. Statistical analysis was conducted using Stata/BE version 17.0. Results: Of the 478 respondents, 243 (50.8%) were females. A larger proportion, 175 (36.6%) were in Pharmacy training, and 156 (32.6%) were in their fifth year of study. The overall mean knowledge score of the participants was 87.9 (SD = 16.1), being higher at 89.6 (SD = 14.3) among medical students and the lowest at 86.7 (SD = 17.1) among Pharmacy students, although this was statistically non-significant (p = 0.488). The overall mean practice score was 60.0 (SD = 24.7), being significantly higher at 63.5 (23.4) among nursing, physiotherapy and environmental students compared to other students (p = 0.048). In multivariable analysis, the participant training program was non-significantly associated with knowledge and practice toward COVID-19. However, increased age (AOR = 1.09, 95% CI: 1.01-1.117) and residing in urban areas (AOR = 1.79, 95% CI: 1.07-3.01) than in rural areas were associated with higher odds of good practice toward COVID-19. Conclusion: The healthcare students generally showed good knowledge levels and poor practices toward COVID-19. Further, there was no evidence of a difference in knowledge of COVID-19 among healthcare students. These findings suggest the need for implementation strategies to be centered on improving the practices of students toward COVID-19.

Thwarting protein synthesis leads to malaria parasite paralysis.

Inhibiting translation presents a tantalizing strategy to tackle the most virulent human malaria parasite. Xie et al. disclose a compound that binds selectively to Plasmodium falciparum tyrosine aminoacyl-tRNA synthetase, preventing the incorporation of tyrosine into nascent proteins and paving the way for a new generation of safe, effective antimalarials.

Structure-Activity Relationship Studies and Plasmodium Life Cycle Profiling Identifies Pan-Active N-Aryl-3-trifluoromethyl Pyrido[1,2- a]benzimidazoles Which Are Efficacious in an in Vivo Mouse Model of Malaria.

Structure-activity relationship studies involving N-aryl-3-trifluoromethyl pyrido[1,2- a]benzimidazoles (PBI) identified several compounds possessing potent in vitro activities against the asexual blood, liver, and gametocyte stages of the Plasmodium parasite with no cross-resistance to chloroquine. Frontrunner lead compounds with good in vitro absorption, distribution, metabolism, and excretion (ADME) profiles were subjected to in vivo proof-of-concept studies in NMRI mice harboring the rodent P. berghei infection. This led to the identification of compounds 10 and 49, effecting 98% and 99.93% reduction in parasitemia with mean survival days of 12 and 14, respectively, at an oral dose of 4 × 50 mg/kg. In vivo pharmacokinetics studies on 10 revealed slow absorption, low volume of distribution, and low clearance profiles. Furthermore, this series displayed a low propensity to inhibit the human ether-a-go-go-related gene (hERG) potassium ion channel whose inhibition is associated with cardiotoxicity.

Structure-Activity Relationship and in Vitro Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) Studies of N-aryl 3-Trifluoromethyl Pyrido[1,2- a]benzimidazoles That Are Efficacious in a Mouse Model of Schistosomiasis.

We have previously reported on the antischistosomal activity of pyrido[1,2- a]benzimidazole (PBI) derivatives. As a follow-up, we designed and prosecuted further structure-activity relationship (SAR) studies that incorporate N-aryl substitutions on the PBI scaffold. Investigations into the in vitro antischistosomal activity against newly transformed schistosomula (NTS) and adult worms revealed several leads with promising potency. Active compounds with a good cytotoxicity profile were tested in vivo whereby 6 and 44 induced noteworthy reduction (62-69%) in the worm load in the Schistosoma mansoni mouse model. Pharmacokinetic analysis on 44 pointed to slow absorption, low volume of distribution, and low plasma clearance indicating the potential of these compounds to achieve a long duration of action. Overall, our work demonstrates that PBI chemotype is a promising scaffold in the discovery of new antischistosomal leads.

Antischistosomal Activity of Pyrido[1,2-a]benzimidazole Derivatives and Correlation with Inhibition of ß-Hematin Formation.

The extensive use of praziquantel against schistosomiasis raises concerns about drug resistance. New therapeutic alternatives targeting critical pathways within the parasite are therefore urgently needed. Hemozoin formation in Schistosoma presents one such target. We assessed the in vitro antischistosomal activity of pyrido[1,2-a]benzimidazoles (PBIs) and investigated correlations with their ability to inhibit ß-hematin formation. We further evaluated the in vivo efficacy of representative compounds in experimental mice and conducted pharmacokinetic analysis on the most potent. At 10 µM, 48/57 compounds resulted in >70% mortality of newly transformed schistosomula, whereas 37 of these maintained >60% mortality of adult S. mansoni. No correlations were observed between ß-hematin inhibitory and antischistosomal activities against both larval and adult parasites, suggesting possible presence of other target(s) or a mode of inhibition of crystal formation that is not adequately modeled by the assay. The most active compound in vivo showed 58.7 and 61.3% total and female worm burden reduction, respectively. Pharmacokinetic analysis suggested solubility-limited absorption and high hepatic clearance as possible contributors to the modest efficacy despite good in vitro activity. The PBIs evaluated in this report thus merit further optimization to improve their efficacy and to elucidate their possible mode of action.

The Role of Natural Products in Drug Discovery and Development against Neglected Tropical Diseases.

Endemic in 149 tropical and subtropical countries, neglected tropical diseases (NTDs) affect more than 1 billion people annually, including 875 million children in developing economies. These diseases are also responsible for over 500,000 deaths per year and are characterized by long-term disability and severe pain. The impact of the combined NTDs closely rivals that of malaria and tuberculosis. Current treatment options are associated with various limitations including widespread drug resistance, severe adverse effects, lengthy treatment duration, unfavorable toxicity profiles, and complicated drug administration procedures. Natural products have been a valuable source of drug regimens that form the cornerstone of modern pharmaceutical care. In this review, we highlight the potential that remains untapped in natural products as drug leads for NTDs. We cover natural products from plant, marine, and microbial sources including natural-product-inspired semi-synthetic derivatives which have been evaluated against the various causative agents of NTDs. Our coverage is limited to four major NTDs which include human African trypanosomiasis (sleeping sickness), leishmaniasis, schistosomiasis and lymphatic filariasis.