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The emergence and spread of drug-recalcitrant Plasmodium falciparum parasites threaten to reverse the gains made in the fight against malaria. Urgent measures need to be taken to curb this impending challenge. The higher plant-derived sesquiterpene, quinoline alkaloids, and naphthoquinone natural product classes of compounds have previously served as phenomenal chemical scaffolds from which integral antimalarial drugs were developed. Historical successes serve as an inspiration for the continued investigation of plant-derived natural products compounds in search of novel molecular templates from which new antimalarial drugs could be developed. The aim of this study was to identify potential chemical scaffolds for malaria drug discovery following analysis of historical data on phytochemicals screened in vitro against P. falciparum. To identify these novel scaffolds, we queried an in-house manually curated database of plant-derived natural product compounds and their in vitro biological data. Natural products were assigned to different structural classes using NPClassifier. To identify the most promising chemical scaffolds, we then correlated natural compound class with bioactivity and other data, namely (i) potency, (ii) resistance index, (iii) selectivity index and (iv) physicochemical properties. We used an unbiased scoring system to rank the different natural product classes based on the assessment of their bioactivity data. From this analysis we identified the top-ranked natural product pathway as the alkaloids. The top three ranked super classes identified were (i) pseudoalkaloids, (ii) naphthalenes and (iii) tyrosine alkaloids and the top five ranked classes (i) quassinoids (of super class triterpenoids), (ii) steroidal alkaloids (of super class pseudoalkaloids) (iii) cycloeudesmane sesquiterpenoids (of super class triterpenoids) (iv) isoquinoline alkaloids (of super class tyrosine alkaloids) and (v) naphthoquinones (of super class naphthalenes). Launched chemical space of these identified classes of compounds was, by and large, distinct from that of legacy antimalarial drugs. Our study was able to identify chemical scaffolds with acceptable biological properties that are structurally different from current and previously used antimalarial drugs. These molecules have the potential to be developed into new antimalarial drugs.

The antimalarial drug-resistance conundrum which threatens to reverse the great strides taken to curb the malaria scourge warrants an urgent need to find novel chemical scaffolds to serve as templates for the development of new antimalarial drugs. Plants represent a viable alternative source for the discovery of unique potential antiplasmodial chemical scaffolds. To expedite the discovery of new antiplasmodial compounds from plants, the aim of this study was to use phylogenetic analysis to identify higher plant orders and families that can be rationally prioritised for antimalarial drug discovery. We queried the PubMed database for publications documenting antiplasmodial properties of natural compounds isolated from higher plants. Thereafter, we manually collated compounds reported along with plant species of origin and relevant pharmacological data. We systematically assigned antiplasmodial-associated plant species into recognised families and orders, and then computed the resistance index, selectivity index and physicochemical properties of the compounds from each taxonomic group. Correlating the generated phylogenetic trees and the biological data of each clade allowed for the identification of 3 hot plant orders and families. The top 3 ranked plant orders were the (i) Caryophyllales, (ii) Buxales, and (iii) Chloranthales. The top 3 ranked plant families were the (i) Ancistrocladaceae, (ii) Simaroubaceae, and (iii) Buxaceae. The highly active natural compounds (IC50 ≤ 1 µM) isolated from these plant orders and families are structurally unique to the legacy antimalarial drugs. Our study was able to identify the most prolific taxa at order and family rank that we propose be prioritised in the search for potent, safe and drug-like antimalarial molecules.

BackgroundDrugs taken during pregnancy can affect maternal and child health outcomes, but few studies have compared the safety and virological efficacy of different antiretroviral therapy (ART) regimens. We report the primary safety outcomes from enrolment up to 50 weeks post partum and a secondary virological efficacy outcome at 50 weeks post partum of three commonly used ART regimens for HIV-1.MethodsIn this multicentre, open-label, randomised, controlled, phase 3 trial, we enrolled pregnant women aged 18 years or older with confirmed HIV-1 infection at 14-28 weeks of gestation. Women were enrolled at 22 clinical research sites in nine countries (Botswana, Brazil, India, South Africa, Tanzania, Thailand, Uganda, the USA, and Zimbabwe). Participants were randomly assigned (1:1:1) to one of three oral regimens: dolutegravir, emtricitabine, and tenofovir alafenamide; dolutegravir, emtricitabine, and tenofovir disoproxil fumarate; or efavirenz, emtricitabine, and tenofovir disoproxil fumarate. Up to 14 days of antepartum ART before enrolment was permitted. Women with known multiple gestation, fetal anomalies, acute significant illness, transaminases more than 2·5 times the upper limit of normal, or estimated creatinine clearance of less than 60 mL/min were excluded. Primary safety analyses were pairwise comparisons between ART regimens of the proportion of maternal and infant adverse events of grade 3 or higher up to 50 weeks post partum. Secondary efficacy analyses at 50 weeks post partum included a comparison of the proportion of women with plasma HIV-1 RNA of less than 200 copies per mL in the combined dolutegravir-containing groups versus the efavirenz-containing group. Analyses were done in the intention-to-treat population, which included all randomly assigned participants with available data. This trial was registered with ClinicalTrials.gov, NCT03048422.FindingsBetween Jan 19, 2018, and Feb 8, 2019, we randomly assigned 643 pregnant women to the dolutegravir, emtricitabine, and tenofovir alafenamide group (n=217), the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group (n=215), and the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (n=211). At enrolment, median gestational age was 21·9 weeks (IQR 18·3-25·3), median CD4 count was 466 cells per μL (308-624), and median HIV-1 RNA was 903 copies per mL (152-5183). 607 (94%) women and 566 (92%) of 617 liveborn infants completed the study. Up to the week 50 post-partum visit, the estimated probability of experiencing an adverse event of grade 3 or higher was 25% in the dolutegravir, emtricitabine, and tenofovir alafenamide group; 31% in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group; and 28% in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (no significant difference between groups). Among infants, the estimated probability of experiencing at least one adverse event of grade 3 or higher by postnatal week 50 was 28% overall, with small and non-statistically significant differences between groups. By postnatal week 50, 14 infants whose mothers were in the efavirenz-containing group (7%) died, compared with six in the combined dolutegravir groups (1%). 573 (89%) women had HIV-1 RNA data available at 50 weeks post partum: 366 (96%) in the dolutegravir-containing groups and 186 (96%) in the efavirenz-containing group had HIV-1 RNA less than 200 copies per mL, with no significant difference between groups.InterpretationSafety and efficacy data during pregnancy and up to 50 weeks post partum support the current recommendation of dolutegravir-based ART (particularly in combination with emtricitabine and tenofovir alafenamide) rather than efavirenz, emtricitabine, and tenofovir disoproxil fumarate, when started in pregnancy.FundingNational Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health.

The aim of the study was to profoundly gain understanding into specific cultural values that underlie traditional practices which pose as barriers to rural girls' education in Zambia. A pairwise case study approach was used to identify and describe types of cultural values prevalent in the Bemba and Tonga ethnic groups of Zambia. A total of 28 interviews (16 focus group discussions and 12 key informant interviews) were carried out with community members and school heads in Choma and Kasama, to verify specific proximate barriers associated with school-going girls. Thematic data analysis was performed using NVivo 12. The study identified six broad values that the two ethnic groups mutually desired. Security and protection, purity and propriety of a woman, conformity, respect, generosity and hard work. Conversely, power and possession, and unity were specific to Tongas and Bembas, respectively. The value of "unity" portrayed more impetus than that of "power and possession" to restrain girls from attending school. While both social groups indicated desire to uphold these values, modes of value expression and collective practices were clearly differentiated. The study established that specific practices and norms chocking rural girls' education are performed through the process of cultural value activation. Further, the study demonstrates that cultural values have underlying associations with rural girls' education advancement especially at higher ages. Gaining detailed knowledge of cultural values underpinning specific social groups through case study research is important in order to inform the design of more effective girls' education promotion interventions.

Simulated standardized patients (SPs) are trained individuals who pose incognito as people seeking treatment in a health care setting. With the method's increasing use and popularity, we propose some standards to adapt the method to contextual considerations of feasibility, and we discuss current issues with the SP method and the experience of consent and ethical research in international SP studies. Since a foundational discussion of the research ethics of the method was published in 2012, a growing number of studies have implemented this method to collect data on the quality of care in a variety of settings around the world. We draw from that experience to provide empirical foundations for a popular approach to ethical approval of such studies in the United States and Canada, which has been to obtain a waiver of informed consent from the health care providers who are the subjects of the research. However, the majority of studies to date have evaluated quality of care outside the U.S., requiring additional ethical consideration when partnering with international institutions. We discuss these considerations in the context of a case study from a completed SP study in South Africa, where informed consent is constitutionally protected.

Using external representations (ERs) to foster content understanding in biology education has increased as they allow for the visualization of abstract biological phenomena. However, the extent to which students have visualization skills required to learn from ERs effectively remains an open question. The current quantitative quasi-experimental research sought to determine the extent to which an animation could be used to enhance students' visualization skills and reduce learning difficulties related to basic concepts of mitosis. Participants were 67 Grade 10 purposively selected learners from a South African school. An assessment test was used for data collection. Results showed that exposure to an animation, as an additional learning tool, improved students' visualization skills while reducing visualization difficulties related to basic concepts of mitosis. We conclude that ERs may enhance students' visualization skills, reduce learning difficulties and improve content understanding. ERs may also be used in broader student development which includes visual literacy.

Our research with Grade 9 learners at a school in Soweto was conducted to explore learners' understanding of fundamental fraction concepts used in applications required at that level of schooling. The study was based on the theory of constructivism in a bid to understand whether learners' transition from whole numbers to rational numbers enabled them to deal with the more complex concept of fractions. A qualitative case study approach was followed. A test was administered to 40 learners. Based on their written responses, eight learners were purposefully selected for an interview. The findings revealed that learners' definitions of fraction were neither complete nor precise. Particularly pertinent were challenges related to the concept of equivalent fractions that include fraction elements, namely the numerator and denominator in the phase of rational number. These gaps in understanding may have originated in the early stages of schooling when learners first conceptualised fractions during the late concrete learning phase. For this reason, we suggest a developmental intervention using physical manipulatives to promote understanding of fractions before inductively guiding learners to construct algorithms and transition to the more abstract applications of fractions required in Grade 9.

This study undertakes a decolonial reading of the Zimbabwean history curriculum as an exemplar of how knowledge and pedagogy could be reframed as the basis for curricular justice in a global imaginary that is predicated on the epistemic hegemony of the Global North. The study which is framed as a conceptual research article introduces and argues for undoing "historicide" as a heuristic within the broader scope of the epistemic decolonial turn. The Zimbabwean history curriculum, as a unit of analysis, is referenced to exemplify entrapment within the Cartesian paradigm of knowing, despite the country's political independence. The argument developed is that history curricula that do not interrogate the geography and biography of knowledge entrench the hegemonic narrative of the coloniality of power and by extension colonial historiography. The paper suggests that the way out of the epistemic quandary that pervades the Zimbabwean history curriculum entails re-envisioning curricular practices in ways that ensure the emergence of a pluriverse in which we reclaim, restitute and legitimate our knowledges and histories, and affirm our ontological densities as equal to those of the Global North.

Use of Information and Communication Technologies (ICTs) offers extraordinary opportunities for society, particularly in the education sector. Many schools in Zimbabwe are now allowing the use of ICTs devices by learners in order to access the Internet and share educational material. However, there is considerable evidence that through use of ICTs, learners will be exposed to different ICTs risks. Learners using ICTs may face Internet and social media related risks which may expose them to inappropriate content, communicating and meeting strangers, cyberbullying, ICTs addiction and cyber-harassment. Sadly, most parents, teachers and learners do not have knowledge and expertise to mitigate these ICTs risks. As such, this research aims to develop an Electronic Safety (E-Safety) framework for Secondary Schools in Zimbabwe that teaches and safeguards learners from ICTs related risks. Researchers used a qualitative research method to gather information on the use of ICTs, risks faced by learners and how these risks can be mitigated. A case study of two secondary schools in Zvishavane District (Zimbabwe) was used. Data was collected using face-to-face interviews and questionnaires from learners. Data from teachers, parents and officials from Ministry of Primary and Secondary Education, Child Protection Services and Ministry of Information Communication and Technology, Postal and Courier Services was collected using face to face interviews. Collected data was analysed using thematic analysis. A framework was then designed by researchers based on the results from the thematic analysis and reviewed by two experts.

IntroductionMedicine prescribing practices are integral to quality of care for leading infectious diseases such as tuberculosis (TB). We describe prescribing practices in South Africa's private health sector, where an estimated third of people with TB symptoms first seek care.MethodsSixteen standardised patients (SPs) presented one of three cases during unannounced visits to private general practitioners (GPs) in Durban and Cape Town: TB symptoms, HIV-positive; TB symptoms, a positive molecular test for TB, HIV-negative; and TB symptoms, history of incomplete TB treatment, HIV-positive. Prescribing practices were recorded in standardised exit interviews and analysed based on their potential to contribute to negative outcomes, including increased healthcare expenditures, antibiotic overuse or misuse, and TB diagnostic delay. Factors associated with antibiotic use were assessed using Poisson regression with a robust variance estimator.ResultsBetween August 2018 and July 2019, 511 SP visits were completed with 212 GPs. In 88.5% (95% CI 85.2% to 91.1%) of visits, at least one medicine (median 3) was dispensed or prescribed and most (93%) were directly dispensed. Antibiotics, which can contribute to TB diagnostic delay, were the most common medicine (76.5%, 95% CI 71.7% to 80.7% of all visits). A majority (86.1%, 95% CI 82.9% to 88.5%) belonged to the WHO Access group; fluoroquinolones made up 8.8% (95% CI 6.3% to 12.3%). Factors associated with antibiotic use included if the SP was asked to follow-up if symptoms persisted (RR 1.14, 95% CI 1.04 to 1.25) and if the SP presented as HIV-positive (RR 1.11, 95% CI 1.01 to 1.23). An injection was offered in 31.9% (95% CI 27.0% to 37.2%) of visits; 92% were unexplained. Most (61.8%, 95% CI 60.2% to 63.3%) medicines were not listed on the South African Primary Healthcare Essential Medicines List.ConclusionPrescribing practices among private GPs for persons presenting with TB-like symptoms in South Africa raise concern about inappropriate antimicrobial use, private healthcare costs and TB diagnostic delay.

As the most stigmatised epidemic in history -- the human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) have proven to be a fierce challenge to humanity. The stigmatisation associated with the HIV/AIDS pandemic continues to destroy societies worldwide. The present study was designed to explain the challenges faced by teachers living with HIV. Transformational and ethics of care theories framed this research study. A narrative research design rooted in social constructivism was used to gather qualitative data. The data were analysed using qualitative content analysis, where descriptive, process, and emotion codes were used to interpret the data. Key findings speak to affected teachers' social exclusion, stigmatisation and discrimination, inadequate care and support, physical debilitation as well as psychological stress and depression. All these conditions resulted in teachers being unable to perform their tasks at optimal level in South African schools.