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The public health measures instituted by governments to combat the coronavirus disease 2019 (COVID-19) may cause developmental and educational losses to adolescents. The impacts of the COVID-19 pandemic and its mitigation strategies on adolescents in sub-Saharan Africa are unclear. This study aimed to examine adolescents’ knowledge, perceptions, and practices related to COVID-19 and the impacts of the pandemic on the daily lives of adolescents in sub-Saharan Africa. The survey was conducted in Burkina Faso, Ethiopia, and Nigeria using computer-assisted telephone interviews to enable rapid and remote data collection. Two sites were included in each country, with approximately 300 adolescents per site and 1,795 adolescents in total. Variations across the six sites were noted for the proportions of the adolescents who could correctly identify all key COVID-19 symptoms (4–25%), transmission methods (16–59%), and prevention approaches (33–79%). Most (> 72%) of the adolescents were no longer going to school due to school closures. Many adolescents (23–81%) were not receiving any education during the pandemic. A considerable proportion of the adolescents (44–83%) self-assessed as having less ability to learn during the pandemic; many expected it to be very difficult to catch up on education after the pandemic. Decreases in the consumption of major food groups were common across sites. Urgent actions are needed in sub-Saharan Africa to address the inadequate knowledge of COVID-19 among adolescents and the impacts of the pandemic on adolescent education and nutrition.

The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented public health crisis globally. Understanding healthcare providers’ (HCPs’) knowledge and perceptions of COVID-19 is crucial to identifying effective strategies to improve their ability to respond to the pandemic in sub-Saharan Africa. A phone-based survey of 900 HCPs in Burkina Faso, Ethiopia, and Nigeria (300 per country) was conducted to assess knowledge, perceptions, COVID-19 prevention measures, stigma, and mental health of HCPs. Modified Poisson regression models were used to evaluate predictors of knowledge, perceptions, and prevention measures; adjusted risk ratios (ARRs) and 95% confidence intervals (CIs) were calculated. Three-fourths of the HCPs had adequate knowledge, and over half had correct perceptions of risk and high levels of self-reported prevention measures. The majority of the HCPs (73.7%) reported self-perceived social stigma. There was relatively low prevalence of depression (6.6%), anxiety (6.6%), or psychological distress (18%). Compared with doctors, being a nurse was associated with lower levels of knowledge (ARR: 0.83; 95% CI: 0.77–0.90) and was also negatively associated with having correct perceptions toward COVID-19 (AOR: 0.82; 95% CI: 0.73–0.92). HCPs treating COVID-19 patients had higher likelihood of having high levels of prevention measures (AOR: 1.37; 95% CI: 1.23–1.53). Despite high levels of knowledge among HCPs in sub-Saharan Africa, there is a need to improve COVID-19 perceptions and compliance with prevention measures as well as address social stigma toward HCPs to better ensure their safety and prepare them to deliver health services.

Coronavirus disease 2019 (COVID-19) is a public health emergency affecting the lives of millions of people globally. Different measures and extraordinary steps are being taken to contain the transmission of the virus. The levels of knowledge and implementation of preventive practices related to COVID-19 in sub-Saharan African countries are unclear. Additionally, there is a lack of evidence regarding the impacts of the pandemic on mental health. This study aimed to describe knowledge and practices related to COVID-19 and to assess mental health status among adults in three sub-Saharan African countries: Burkina Faso, Ethiopia, and Nigeria. A total of 1,797 adults were included in the survey, and data were collected using computer-assisted telephone interviews. The proportions of adults who identified more than 80% of COVID-19 symptoms, transmission methods, and prevention mechanisms were 69.9%, 79.2%, and 90.7%, respectively. The practice of preventive measures was relatively lower for avoiding social gatherings and disinfecting contaminated surfaces. Better education, urban residence, and believing the pandemic is real were factors associated with good knowledge on COVID-19 symptoms, transmission methods, and preventive actions. Additionally, being male was associated with good knowledge on symptoms and transmission methods, whereas being in an older age group was associated with knowledge of transmission methods. Mild, moderate, and severe psychological distress was reported by 20.6%, 5.9%, and 1.1% of the participants, respectively. Although this study found high levels of knowledge regarding COVID-19, interventions are needed to increase the uptake of recommended preventive practices among adults in sub-Saharan Africa.

The coronavirus disease 2019 (COVID-19) pandemic has significant health and economic ramifications across sub-Saharan Africa (SSA). Data regarding its far-reaching impacts are severely lacking, thereby hindering the development of evidence-based strategies to mitigate its direct and indirect health consequences. To address this need, the Africa Research, Implementation Science, and Education (ARISE) Network established a mobile survey platform in SSA to generate longitudinal data regarding knowledge, attitudes, and practices (KAP) related to COVID-19 prevention and management and to evaluate the impact of COVID-19 on health and socioeconomic domains. We conducted a baseline survey of 900 healthcare workers, 1,795 adolescents 10 to 19 years of age, and 1,797 adults 20 years or older at six urban and rural sites in Burkina Faso, Ethiopia, and Nigeria. Households were selected using sampling frames of existing Health and Demographic Surveillance Systems or national surveys when possible. Healthcare providers in urban areas were sampled using lists from professional associations. Data were collected through computer-assisted telephone interviews from July to November 2020. Consenting participants responded to surveys assessing KAP and the impact of the pandemic on nutrition, food security, healthcare access and utilization, lifestyle, and mental health. We found that mobile telephone surveys can be a rapid and reliable strategy for data collection during emergencies, but challenges exist with response rates. Maintaining accurate databases of telephone numbers and conducting brief baseline in-person visits can improve response rates. The challenges and lessons learned from this effort can inform future survey efforts during COVID-19 and other emergencies, as well as remote data collection in SSA in general.

To examine knowledge of menstruation, HIV and STIs other than HIV across eight sites in SSA to develop effective programmatic interventions enabling adolescents to achieve positive SRH as their transition to adulthood.We combine data from eight Health and Demographic Surveillance Sites across sub-Saharan Africa, from an adolescent-specific survey that included 7116 males and females age 10-19 years old. We provide pooled and site-specific estimates from multiple analytic models examining the how year-specific age, school attendance and work correlate with knowledge of menstruation, HIV knowledge and knowledge of sexually transmitted infections (STIs) other than HIV.Many adolescents lack knowledge of menstruation (37.3%, 95% CI 31.8, 43.1 do not know of menstruation) and STIs other than HIV (55.9%, 95% CI 50.4, 61.3 do not know of other STIs). In multivariate analysis, older age, being in school and wealth are significant positive correlates of STI knowledge. Older adolescent age, female sex and being in school are significant positive correlates of knowledge of menstruation. Knowledge of HIV is high (89.7%, 95% CI 8.3, 12.7 know of HIV) and relatively similar across adolescent age, sex, wealth and school and work attendance.Knowledge of HIV is widespread across adolescents in these communities in sub-Saharan Africa, but knowledge of other dimensions of sexual and reproductive health - menstruation and other STIs in this study - is lacking especially for early adolescents (10- to 14-year olds). The dissemination of more comprehensive sexual and reproductive health information is needed within these and similar communities in SSA to help adolescents gain insight on how to make their own decisions towards positive adolescent sexual and reproductive health and protect them from risks.Examiner les connaissances sur la menstruation, le VIH et les IST autres que le VIH dans huit sites d’Afrique subsaharienne (ASS) afin d’élaborer des programmes d’interventions efficaces permettant aux adolescents d’obtenir une santé sexuelle et reproductive (SSR) positive lorsqu’ils passent à l’âge adulte. MÉTHODES: Nous combinons ici les données de huit sites de Surveillance Démographique et de Santé en Afrique subsaharienne, à partir d'une enquête spécifique réalisée auprès d'adolescents et comprenant 7.116 hommes et femmes âgés de 10 à 19 ans. Nous fournissons des estimations poolées et spécifiques à chaque site à partir de plusieurs modèles analytiques examinant la corrélation entre l'âge, la fréquentation scolaire et le travail, avec les connaissances sur la menstruation, sur le VIH et sur les IST autres que le VIH. RÉSULTATS: Beaucoup d'adolescents manquaient de connaissance sur les menstruations (37,3% ; IC95%: 31,8-43,1 ne connaissaient pas les menstruations) et les IST autres que le VIH (55,9% ; IC95%: 50,4-61,3 ne connaissent pas d'autres IST). Dans l'analyse multivariée, l'âge plus avancé, la fréquentation scolaire et la richesse sont des corrélats positifs significatifs des connaissances sur les IST. L’âge adolescent plus avancé, le sexe féminin et le fait d’être à l’école sont des corrélats positifs significatifs pour les connaissances sur la menstruation. Les connaissances sur le VIH sont élevées (89,7%, IC95%: 8,3-12,7 sont au courant du VIH) et relativement similaires selon les âges des adolescents, le sexe, la richesse et la fréquentation scolaire et le travail.Les connaissances sur le VIH semblent être répandues parmi les adolescents de ces communautés en Afrique subsaharienne, mais les connaissances sur les autres aspects de la santé sexuelle et reproductive - menstruations et autres IST dans cette étude - semblent faire défaut, en particulier chez les jeunes adolescents (âgés de 10 à 14 ans). La dissémination de telles informations plus complètes est nécessaire au sein de ces communautés et de communautés similaires en ASS afin d’aider les adolescents à comprendre comment prendre leurs propres décisions en matière de santé sexuelle et reproductive et de les protéger contre les risques.

To measure health-related behaviours and risk factors among sub-Saharan African adolescents.Cross-sectional study in nine communities in Burkina Faso, Ethiopia, Eswatini, Ghana, Nigeria, Tanzania and Uganda between 2015 and 2017. Community-representative samples of males and females 10-19 years of age were selected. All communities used a uniform questionnaire that was adapted from the WHO Global School-based Student Health Survey. Weighted prevalence estimates and 95% confidence intervals were calculated for each indicator and stratified by age and sex using SAS version 9.4. All prevalence estimates were pooled across communities through random-effects meta-analyses in Stata version 14.A total of 8075 adolescents participated in the study. We observed a high prevalence of inadequate fruit consumption (57-63%) and low physical activity (82-90%); a moderate prevalence of inadequate vegetable consumption (21-31%), unprotected last sex (38-45%), age at first sex15 years (21-28%) and bullying and physical fighting (12-35%); and a low prevalence of mental health risk factors (1-11%) and alcohol and substance use risk factors (0-6%). We observed a moderate to high prevalence of daily soft drink consumption (21-31%) for all adolescents. Among sexually active adolescents 15-19 years, 37% of females reported ever being pregnant and 8% of males reported to have ever made someone pregnant. Bullying (23%) and physical fighting (35%) were more common among younger male adolescents . The prevalence of low mood was generally higher among older (15-19 years) than younger adolescents (10-14 years). The proportion of adolescents reporting alcohol, drug or cigarette use was very small, with the exception of khat use in Ethiopia.Overall, diet and physical activity, violence, sexual and reproductive health, and depression are important risk factors for these sub-Saharan African communities. These findings suggest that more evidence is needed including novel efforts for the collection of sensitive information, as well as a need to move towards community-tailored interventions to reach adolescent populations with varying needs.Mesurer les comportements liés à la santé et les facteurs de risque chez les adolescents africains subsahariens. MÉTHODES: Etude transversale dans neuf communautés au Burkina Faso, en Ethiopie, à Eswatini, au Ghana, au Nigéria, en Tanzanie et en Ouganda entre 2015 et 2017. Des échantillons représentatifs de la communauté composés d'hommes et de femmes âgés de 10 à 19 ans ont été sélectionnés. Toutes les communautés ont utilisé un questionnaire uniforme adapté de l'Enquête Mondiale sur la Santé des Elèves de l'OMS. Les estimations de prévalence pondérée et les intervalles de confiance à 95% ont été calculés pour chaque indicateur et stratifiées par âge et sexe à l'aide de la version 9.4 de SAS. Toutes les estimations de prévalence ont été poolées dans les communautés via des méta-analyses à effets aléatoires dans Stata, version 14. RÉSULTATS: 8.075 adolescents ont participé à l'étude. Nous avons observé une prévalence élevée de consommation insuffisante de fruits (57-63%) et de faible activité physique (82-90%); une prévalence modérée de consommation insuffisante de légumes (21-31%), du dernier rapport sexuel non protégé (38-45%), du premier rapport sexuel à moins de 15 ans (21-28%) et de l'intimidation et des combats physiques (12-35%), une faible prévalence de facteurs de risque pour la santé mentale (1-11%) et de facteurs de risque pour la consommation d'alcool et de substances (0-6%). Nous avons observé une prévalence modérée à élevée de consommation quotidienne de boissons gazeuses (21-31%) chez tous les adolescents. Parmi les adolescents sexuellement actifs âgées de 15 à 19 ans, 37,0% des femmes ont déclaré avoir déjà été enceintes et 8,0% des hommes ont rapporté avoir déjà enceinté une femme. L'intimidation (23%) et les combats physiques étaient plus fréquents chez les adolescents plus jeunes (35%). La prévalence de la mauvaise humeur était généralement plus élevée chez les adolescents d’âge plus élevé (de 15 à 19 ans) que chez les plus jeunes (de 10 à 14 ans). La proportion d'adolescents déclarant avoir consommé de l'alcool, des drogues ou des cigarettes était très faible, à l'exception de la consommation de khat en Ethiopie.Dans l’ensemble, le régime alimentaire et l’activité physique, la violence, la santé sexuelle et reproductive et la dépression sont des facteurs de risque importants pour ces communautés d’Afrique subsaharienne. Ces résultats suggèrent que davantage de données sont nécessaires, notamment de nouveaux efforts pour la collecte d'informations sensibles, ainsi que la nécessité de passer à des interventions adaptées aux communautés pour atteindre les populations adolescentes avec des besoins variés.

Background The development and spread of artemisinin-resistant Plasmodium falciparum malaria in Greater Mekong Subregion has created impetus for continuing global monitoring of efficacy of artemisinin-based combination therapies (ACTs). This post analyses is aimed to evaluate changes in early treatment response markers 10 years after the adoption of ACTs as first-line treatments of uncomplicated falciparum malaria in Nigeria. Methods At 14 sentinel sites in six geographical areas of Nigeria, we evaluated treatment responses in 1341 children under 5 years and in additional 360 children under 16 years with uncomplicated malaria enrolled in randomized trials of artemether-lumefantrine versus artesunate-amodiaquine at 5-year interval in 2009–2010 and 2014–2015 and at 2-year interval in 2009–2010 and 2012–2015, respectively after deployment in 2005. Results Asexual parasite positivity 1 day after treatment initiation (APPD1) rose from 54 to 62% and 2 days after treatment initiation from 5 to 26% in 2009–2010 to 2014–2015 (P = 0.002 and P 75 000 μl− 1, haematocrit > 27% 1 day post-treatment initiation, treatment with artemether-lumefantrine and enrolment in 2014–2015 independently predicted APPD1. In parallel, Kaplan-Meier estimated risk of recurrent infections by day 28 rose from 8 to 14% (P = 0.005) and from 9 to 15% (P = 0.02) with artemether-lumefantrine and artesunate-amodiaquine, respectively. Mean asexual parasitaemia half-life increased significantly from 1.1 h to 1.3 h within 2 years (P

The coronavirus disease 2019 (COVID-19) pandemic may have short-term and long-term impacts on health services across sub-Saharan African countries. A telephone survey in Burkina Faso, Ethiopia, and Nigeria was conducted to assess the effects of the pandemic on healthcare services from the perspectives of healthcare providers (HCPs) and community members. A total of 900 HCPs (300 from each country) and 1,797 adult community members (approximately 600 from each country) participated in the study. Adjusted risk ratios (ARRs) and 95% confidence intervals (CIs) were computed using modified Poisson regression. According to the HCPs, more than half (56%) of essential health services were affected. Child health services and HIV/surgical/other services had a slightly higher percentage of interruption (33%) compared with maternal health services (31%). A total of 21.8%, 19.3%, and 7.7% of the community members reported that their family members and themselves had difficulty accessing childcare services, maternal health, and other health services, respectively. Nurses had a lower risk of reporting high service interruptions than physicians (ARR, 0.85; 95% CI, 0.56–0.95). HCPs at private facilities (ARR, 0.71; 95% CI, 0.59–0.84) had a lower risk of reporting high service interruptions than those at governmental facilities. Health services in Nigeria were more likely to be interrupted than those in Burkina Faso (ARR, 1.38; 95% CI, 1.19–1.59). Health authorities should work with multiple stakeholders to ensure routine health services and identify novel and adaptive approaches to recover referral services, medical care, maternal and child health, family planning, immunization and health promotion, and prevention during the COVID-19 era.

Objectives COVID-19 has far-reaching consequences for developing countries through the combined effects of infection and mortality and unintended consequences from mitigation measures. COVID-19 can adversely impact food systems and dietary diversity for populations. This cross-sectional study evaluated, using a mobile platform, the effect of COVID-19 on food prices and dietary diversity and quality, among 1797 households in Nouna and Ouagadougou (Burkina Faso), Addis Ababa and Kersa (Ethiopia), and Lagos and Ibadan (Nigeria). Methods Dietary intake was assessed as the frequency of consumption of 20 food groups over the previous 7 days. Dietary diversity scores (DDS; range: 0–10) and Prime Diet Quality Score (PDQS; range: 0–40) assessed dietary diversity and quality. Linear regression models were used to evaluate associations between changes in the prices of staples, pulses, vegetables, fruits, and animal source foods (ASF) with DDS and PDQS during COVID-19. Results Most households reported increases in prices of staples, pulses, fruits, vegetables and ASF, and ≥40% reported decreased consumption of staples, legumes, ASF, other vitamin A rich vegetables, other vegetables and other fruits, and lower DDS and PDQS compared to the period before the COVID-19 emergency. Increases in pulse prices were associated with lower DDS (estimate − 0.35, 95% CI: −0.61, −0.09). Lower crop production (estimate − 0.70, 95% CI: −1.02, −0.37), and skipping meals (estimate − 0.39, 95% CI: −0.56, −0.21) or not eating for a whole day (estimate − 0.23, 95% CI: −0.43, −0.03) were also associated with lower DDS. Conclusions The price increases and worsening dietary diversity and quality call for social protection and other strategies to increase the availability and affordability of nutrient-rich foods during the COVID-19 pandemic and other public health emergencies. Funding Sources The Bill and Melinda Gates Foundation Grant as well as institutional support from the Heidelberg Institute of Global Health, Germany and the Harvard T.H. Chan School of Public Health, USA, supported this work.

The ARISE Network Adolescent Health Study is an exploratory, community-based survey of 8075 adolescents aged 10-19 in 9 communities in 7 countries: Burkina Faso, Eswatini, Ethiopia, Ghana, Nigeria, Tanzania and Uganda. Communities were selected opportunistically and existing population cohorts maintained by health and demographic surveillance systems (HDSSs). The study is intended to serve as a first round of data collection for African adolescent cohorts, with the overarching goal of generating community-based data on health-related behaviours and associated risk factors in adolescents, to identify disease burdens and health intervention opportunities. Household-based sampling frames were used in each community to randomly select eligible adolescents (aged 10-19 years). Data were collected between July 2015 and December 2017. Consenting participants completed face-to-face interviews with trained research assistants using a standardised questionnaire, which covered physical activity, cigarette and tobacco use, substance and drug use, mental health, sexual behaviours and practices, sexually transmitted infections, pregnancy, food security and food diversity, teeth cleaning and hand washing, feelings and friendship, school and home activities, physical attacks and injuries, health care, health status assessment and life satisfaction, as well as media and cell phone use and socio-demographic and economic background characteristics. Results from this multi-community study serve to identify major adolescent health risks and disease burdens, as well as opportunities for interventions and improvements through policy changes.L’étude ARISE du réseau sur la santé des adolescents est une étude exploratoire de surveillance basée sur la communauté portant sur 8.075 adolescents âgés de 10 à 19 ans dans 9 communautés de 7 pays: Burkina Faso, Eswatini, Ethiopie, Ghana, Nigéria, Tanzanie et Ouganda. Les communautés ont été sélectionnés de manière opportuniste et les cohortes de population existantes maintenues par des systèmes de surveillance de la santé et démographique (SSSD). L'étude est destinée à servir comme premier cycle de collecte de données pour les cohortes d’adolescents africains, dans le but primordial de générer des données communautaires sur les comportements liés à la santé et les facteurs de risque associés chez les adolescents, afin d'identifier la charge de morbidité et les opportunités d'intervention en matière de santé. Des cadres d'échantillonnage basés sur le ménage ont été utilisés dans chaque communauté pour sélectionner au hasard les adolescents admissibles (âgés de 10-19 ans). Les données ont été collectées entre juillet 2015 et décembre 2017. Les participants consentants ont participé à des entretiens de face à face avec des assistants de recherche formés, à l'aide d'un questionnaire standardisé couvrant l'activité physique, l’usage de la cigarette ou la consommation de tabac, l'usage de drogues et autres substances, la santé mentale, les comportements et pratiques sexuels, les infections sexuellement transmissibles, la grossesse, la sécurité et la diversité alimentaire, le nettoyage des dents et le lavage des mains, les sentiments et les amitiés, les activités scolaires et à domicile, les attaques et les blessures physiques, les soins de santé, l’évaluation de l’état de santé et la satisfaction à l’égard de la vie, l’utilisation des médias et du téléphone portable ainsi que les caractéristiques sociodémographiques et économiques. Les résultats de cette étude portant sur plusieurs communautés permettent d'identifier les principaux risques pour la santé des adolescents et les charges de morbidité, ainsi que les opportunités d'interventions et d'amélioration par le biais de changements de politiques.

Resistance in Plasmodium falciparum to amodiaquine (AQ) can be reversed in vitro with with antihistaminic and tricyclic antidepressant compounds, but its significance in vivo is unclear. The present report presents the enhancement of the antimalarial efficacy of AQ by chlorpheniramine, an H1 receptor antagonist that reverses chloroquine (CQ) resistance in vitro and enhances its efficacy in vivo, in five children who failed CQ and/or AQ treatment, and who were subsequently retreated and cured with a combination of AQ plus CP, despite the fact that parasites infecting the children harboured mutant pfcrtT76 and pfmdr1Y86 alleles associated with AQ resistance. This suggests a potential clinical application of the reversal phenomenon.

Seven methanol extracts of seven plants from seven plant families were screened for antimalarial properties. The plants were identified and selected from Gboko and Kastina-Ala local government areas in the Tivland ethnobotany in the Middle Belt Zone of Nigeria. Methanol plant extracts were evaluated for in vitro. antimalarial properties using the lactate dehydrogenase technique, with a multiresistant strain of Plasmodium falciparum. K1. Quantification of activity was by estimation of the concentration of extracts that inhibited 50% growth of parasite (IC50) in µg/ml. Of the seven plants screened, Erythrina senegalensis. DC (Leguminosae), Pericopsis elata. Harms (Papilionaceae), and Bridelia micrantha. Benth (Fabaceae) had IC50 values of 99.7, 124.8, and 158.7 µg/ml, respectively. Nauclea latifolia. SM (Rubiaceae) extract exhibited the least activity in the assay with an IC50 value of 478.9 µg/ml.

The efficacy of chloroquine and chloroquine plus chloropheniramine, a histamine H1 receptor blocker which reverses chloroquine insensitivity in Plasmodium falciparum in vitro, was studied in 96 children with acute symptomatic uncomplicated falciparum malaria. The chloroquine/chloropheniramine combination produced a significantly higher cure rate than chloroquine alone and cured 77% of children with chloroquine treatment failures. Children with chloroquine treatment failure had mean plasma chloroquine concentrations above the minimum therapeutic concentration for the area. Chloroquine concentrations in plasma and red blood cells and ratio of red cell to plasma chloroquine concentrations on days 3 and 7 after initiation of therapy were not significantly different in the two groups. Chloroquine/chloropheniramine produces a higher cure rate than chloroquine alone and reverses chloroquine insensitivity in Plasmodium falciparum in vivo. It may be a useful way of optimising the antimalarial effect of chloroquine.

Drug resistance inPlasmodium falciparumrequires that new drugs must be developed. Plants are a potential source for drug discovery and development. Two plants that used to treat febrile illnesses in Nigeria were tested forin vitroandin vivoantimalarial activity and cytotoxicity in cancer cell lines. Methanol, hexane, and ethyl acetate leaf extracts ofFicus thonningiiandLophira alatawere active inin vitroassays againstP. falciparumNF54 (sensitive) and K1 (multiresistant) strains. Hexane extracts ofF. thonningiiandL. alatawere the most effective extracts inin vitroassays with IC50of2.7±1.6 μg/mL and2.5±0.3 μg/mL for NF54 and10.4±1.6 μg/mL and2.5±2.1 μg/mL for K1 strain. All extracts were nontoxic in cytotoxicity assays against KB human cell line with IC50of over 20 μg/mL, demonstrating selectivity againstP. falciparum.In vivoanalysis shows that hexane extracts of both plants reduced parasitaemia. At the maximum dose tested,L. alatahad a 74.4% reduction of parasitaemia whileF. thonningiihad a reduction of 84.5%, both extracts prolonged animal survival in mice infected withP. bergheiNK65 when compared with vehicle treated controls. The antiplasmodial activity observed justifies the use of both plants in treating febrile conditions.

Malaria parasites are sexually reproducing protozoa, although the extent of effective meiotic recombination in natural populations has been debated. If meiotic recombination occurs frequently, compared with point mutation and mitotic rearrangement, linkage disequilibrium between polymorphic sites is expected to decline with increasing distance along a chromosome. The rate of this decline should be proportional to the effective meiotic recombination rate in the population. Multiple polymorphic sites covering a 5-kb region of chromosome 9 (the msp1 gene) have been typed in 547 isolates from six populations in Africa to test for such a decline and estimate its rate in populations of Plasmodium falciparum . The magnitude of two-site linkage disequilibrium declines markedly with increasing molecular map distance between the sites, reaching nonsignificant levels within a map range of 0.3–1.0 kb in five of the populations and over a larger map distance in the population with lowest malaria endemicity. The rate of decline in linkage disequilibrium over molecular map distance is at least as rapid as that observed in most chromosomal regions of other sexually reproducing eukaryotes, such as humans and Drosophila . These results are consistent with the effective recombination rate expected in natural populations of P. falciparum , predicted on the basis of the underlying molecular rate of meiotic crossover and the coefficient of inbreeding caused by self-fertilization events. This is conclusive evidence to reject any hypothesis of clonality or low rate of meiotic recombination in P. falciparum populations. Moreover, the data have major implications for the design and interpretation of population genetic studies of selection on P. falciparum genes.

The effect of combining promethazine with chloroquine was examined against Plasmodium falciparum in vitro in the Aotus-P. falciparum model and in bioassays from volunteers given promethazine. The combination of chloroquine plus promethazine (1 x 10(-6) M) reversed chloroquine resistance in standard P. falciparum clones and patient parasite isolates from Nigeria. The combination reduced the 50% inhibitory concentrations (IC50s) for chloroquine against resistant parasites by 32-92%. Coadministration of promethazine with chloroquine also demonstrated a dose-dependent effect in Aotus monkeys infected with chloroquine-resistant P. falciparum. Monkeys were given a chloroquine dose (20 mg/kg of body weight for seven days), which normally has no effect on parasitemia, plus 10, 20, 40, or 80 mg of promethazine/kg of body weight. In one monkey, parasitemia was suppressed at the lowest promethazine dose, but re-treatment with 20 mg/kg resulted in clearance of parasitemia. Initial treatment with chloroquine and 20 or 40 mg/kg of promethazine cleared parasitemia in some animals followed by recrudescence. Re-treatment at higher doses cured one monkey and resulted in initial clearance and delayed recrudescence 28 or 63 days after treatment in two monkeys. Recrudescent parasitemia in the two monkeys was low (10 parasites/microl of blood) and subsequently cleared without re-treatment. An in vitro bioassay model was developed to examine the effects of clinically achievable doses of promethazine on parasites susceptibilities in vitro. Plasma samples taken at hourly intervals from patients given a single oral dose of 25 mg of promethazine decreased the IC50 values for chloroquine by 20-58% with the most significant reductions occurring in plasma obtained from volunteers 3-4 hr after ingestion. Plasma obtained from two volunteers 6 hr after ingestion of the drug demonstrated no effect on chloroquine susceptibility, suggesting that study of the pharmacokinetic disposition and potential interaction is warranted to optimize the dose regimen in patients for antimalarial efficacy. Historic use of this drug combination for treatment or prevention of chloroquine-associated pruritus or as an antiemetic suggest that the combination is safe and effective when used at standard dosages. The results from this study demonstrate that promethazine is a potent modulator of chloroquine resistance. Clinical evaluation of therapeutic regimens is required to validate clinical efficacy of this promising combination for treatment of uncomplicated chloroquine-resistant malaria.

In a previous report we described the synergistic antimalarial interaction between two structurally similar compounds, rufigallol and exifone. To explain this phenomenon, we proposed that exifone is transformed inside the parasitized erythrocyte into a xanthone with potent antimalarial properties. We speculated that the transformation process was induced by the prooxidant activity of rufigallol. On the basis of this model we hypothesized that exifone would act synergistically with other oxidant drugs. In the present study we have found a similar synergistic interaction between exifone and ascorbic acid (vitamin C) against both chloroquine-susceptible and multidrug-resistant strains of Plasmodium falciparum. The prooxidant activity of ascorbic acid against Plasmodium-infected erythrocytes is believed to result from an intraerythrocytic Fenton reaction occurring in the acidic food vacuole of the parasite. The hydroxyl radicals produced during this process are believed to attack exifone, which undergoes cyclodehydration to become 2,3,4,5,6-pentahydroxyxanthone (X5). Evidence presented to support this "xanthone hypothesis" includes the demonstration that the exifone ==> X5 transformation occurs readily in vitro under mildly acidic conditions in the presence of iron, ascorbic acid, and oxygen.

Antigens associated with the surface of merozoites of the malaria parasite Plasmodium falciparum are directly accessible to immune attack and therefore are prime vaccine candidates. We have previously shown that one of the two known merozoite surface antigens (merozoite surface antigen 2; MSA-2) exhibits considerable sequence and antigenic diversity in different isolates. The sequences of MSA-2 from three isolates revealed a central domain composed of repeats that vary in number, length, and sequence, flanked in turn by nonrepetitive variable sequences and by conserved N- and C-terminal domains. We report here the sequences of a further four MSA-2 alleles, containing repetitive sequences that are related but not identical to each other. The seven alleles of MSA-2 can be divided into two distinct allele families on the basis of nonrepetitive sequences. Hybridization studies with repeat probes indicated that all of the 44 P. falciparum isolates examined contained repeat regions similar to those defined in known MSA-2 sequences.

Summary Background Artemisinin-based combination antimalarials are currently considered effective alternatives for the treatment of malaria in Africa, but there are few studies of such combinations in Nigerian children. We assessed the safety, treatment efficacy and effects on gametocyte carriage of the combination of artesunate plus amodiaquine and chloroquine plus pyrimethamine-sulfadoxine in children. Methods We evaluated 153 children who were aged 12 years or younger who had uncomplicated Plasmodium falciparum malaria. Patients were randomly assigned a combination of artesunate (4 mg/kg of body weight daily for 3 days) plus amodiaquine (30 mg/kg over 3 days), or chloroquine (25 mg/kg over 3 days) plus pyrimethamine-sulfadoxine (25 mg/kg of the sulfadoxine component at presentation). The primary endpoints were the proportions of children with adequate clinical and parasitological response, late parasitological failure, late clinical failure and early treatment failure. The parasitological cure rates on days 14–28 were also used as the primary endpoints. Results Both regimens were well tolerated; no child was withdrawn because of drug intolerance. All children treated with artesunate plus amodiaquine had adequate clinical and parasitological response (ACPR), while all but five children treated with chloroquine plus pyrimethamine-sulfadoxine had similar response. Fever clearance times were similar in the two treatment groups. However, the proportion of patients whose parasitaemia cleared by day 2 was significantly higher (100 vs. 50%, P = 0.00001) and parasite clearance was significantly faster (1.7 ± 0.4 vs. 2.5 ± 0.8 days, P = 0.0001) in children treated with artesunate plus amodiaquine. The cure rates on days 21 (100%vs. 94%, P = 0.03) and 28 (100%vs. 90%, P = 0.003) were also significantly higher in children treated with artesunate plus amodiaquine than in those treated with chloroquine plus pyrimethamine-sulfadoxine. Overall, a significantly higher proportion of children treated with chloroquine plus pyrimethamine-sulfadoxine carried gametocytes at least once during follow-up compared with those treated with artesunate plus amodiaquine [5 of 50 (10%) vs. 1 of 103 (0.97%), P = 0.01]. Conclusion The combination of artesunate plus amodiaquine is therapeutically superior to a combination of chloroquine plus pyrimethamine-sulfadoxine, and significantly reduced gametocyte carriage following treatment.

Wellcome Trust (Grant Ref. 055487/Z/98/Z) and the Medical Research Council (Grant Ref. G9803180). London School of Hygiene and Tropical Medicine. Department of Infectious and Tropical Diseases. Keppel Street, London, UK. Minist?rio da Sa?de. Funda??o Nacional de Sa?de. Instituto Evandro Chagas. Bel?m, PA, Brasil. Universiti Malaysia Sarawakc. Faculty of Medicine and Health Sciences. Kota Samarahan, Sarawak, Malaysia. London School of Hygiene and Tropical Medicine. Department of Infectious and Tropical Diseases. Keppel Street, London, UK. London School of Hygiene and Tropical Medicine. Department of Infectious and Tropical Diseases. Keppel Street, London, UK. Minist?rio da Sa?de. Funda??o Nacional de Sa?de. Instituto Evandro Chagas. Bel?m, PA, Brasil. University of Ibadan. College of Medicine. Postgraduate Institute of Medical Research and Training. Ibadan, Nigeria. London School of Hygiene and Tropical Medicine. Department of Infectious and Tropical Diseases. Keppel Street, London, UK. Comparing patterns of genetic variation at multiple loci in the genome of a species can potentially identify loci which are under selection. The large number of polymorphic microsatellites in the malaria parasite Plasmodium falciparum are available markers to screen for selectively important loci. The Pfs48/45 gene on Chromosome 13 encodes an antigenic protein located on the surface of parasite gametes, which is a candidate for a transmission blocking vaccine. Here, genotypic data from 255 P. falciparum isolates are presented, which show that alleles and haplotypes of five single nucleotide polymorphisms (SNPs) in the Pfs48/45 gene are exceptionally skewed in frequency among different P. falciparum populations, compared with alleles at 11 microsatellite loci sampled widely from the parasite genome. Fixation indices measuring inter-population variance in allele frequencies (FST) were in the order of four to seven times higher for Pfs48/45 than for the microsatellites, whether considered (i) among populations within Africa, or (ii) among different continents. Differing mutational processes at microsatellite and SNP loci could generally affect the population structure at these different types of loci, to an unknown extent which deserves further investigation. The highly contrasting population structure may also suggest divergent selection on the amino acid sequence of Pfs48/45 in different populations, which plausibly indicates a role for the protein in determining gamete recognition and compatibility. ? 2001 Elsevier Science B.V.

New strategies are required to identify the most important targets of protective immunity in complex eukaryotic pathogens. Natural selection maintains allelic variation in some antigens of the malaria parasite Plasmodium falciparum. Analysis of allele frequency distributions could identify the loci under most intense selection. The merozoite surface protein 1 (Msp1) is the most-abundant surface component on the erythrocyte-invading stage of P. falciparum. Immunization with whole Msp1 has protected monkeys completely against homologous and partially against non-homologous parasite strains. The single-copy msp1 gene, of about 5 kilobases, has highly divergent alleles with stable frequencies in endemic populations. To identify the region of msp1 under strongest selection to maintain alleles within populations, we studied multiple intragenic sequence loci in populations in different regions of Africa and Southeast Asia. On both continents, the locus with the lowest inter-population variance in allele frequencies was block 2, indicating selection in this part of the gene. To test the hypothesis of immune selection, we undertook a large prospective longitudinal cohort study. This demonstrated that serum IgG antibodies against each of the two most frequent allelic types of block 2 of the protein were strongly associated with protection from P. falciparum malaria.

Financial support was provided by The Wellcome Trust (grant ref. 055487), the European Commission, and the University of London Central Research Fund London School of Hygiene and Tropical Medicine. Department of Infectious and Tropical Diseases. Keppel St, London, UK. London School of Hygiene and Tropical Medicine. Department of Infectious and Tropical Diseases. Keppel St, London, UK. London School of Hygiene and Tropical Medicine. Department of Infectious and Tropical Diseases. Keppel St, London, UK. London School of Hygiene and Tropical Medicine. Department of Infectious and Tropical Diseases. Keppel St, London, UK. London School of Hygiene and Tropical Medicine. Department of Infectious and Tropical Diseases. Keppel St, London, UK. London School of Hygiene and Tropical Medicine. Department of Infectious and Tropical Diseases. Keppel St, London, UK. London School of Hygiene and Tropical Medicine. Department of Infectious and Tropical Diseases. Keppel St, London, UK. University of Ibadan. College of Medicine. Ibadan, Nigeria. Organisation de Coordination pour la lutte contre les End?mies en Afrique Centrale. Malaria Department. Yaounde, Cameroon. Minist?rio da Sa?de. Funda??o Nacional de Sa?de. Instituto Evandro Chagas. Bel?m, PA, Brasil. Universiti Malaysia Sarawak. Kota Samarahan. Sarawak, Malaysia. Biomedical Primate Research Centre. Rijswijk, The Netherlands. The origin and geographical spread of Plasmodium falciparum is here determined by analysis of mitochondrial DNA sequence polymorphism and divergence from its most closely related species P. reichenowi (a rare parasite of chimpanzees). The complete 6 kb mitochondrial genome was sequenced from the single known isolate of P. reichenowi and from four different cultured isolates of P. falciparum, and aligned with the two previously derived P. falciparum sequences. The extremely low synonymous nucleotide polymorphism in P. falciparum (pi=0.0004) contrasts with the divergence at such sites between the two species (kappa=0.1201), and supports a hypothesis that P. falciparum has recently emerged from a single ancestral population. To survey the geographical distribution of mitochondrial haplotypes in P. falciparum, 104 isolates from several endemic areas were typed for each of the identified single nucleotide polymorphisms. The haplotypes show a radiation out of Africa, with unique types in Southeast Asia and South America being related to African types by single nucleotide changes. This indicates that P. falciparum originated in Africa and colonised Southeast Asia and South America separately.

The emergence of chloroquine resistance in Plasmodium falciparum has necessitated the development of alternate strategies for chemotherapy and chemoprophylaxis. One approach has been the identification of drugs that do not possess any intrinsic antimalarial activity when used alone but that potentiate the effect of currently available antimalarial drugs, such as chloroquine. We identified fluoxetine hydrochloride (Prozac), a commonly prescribed antidepressant, as another resistance modulator for drug-resistant P. falciparum. Studies with chloroquine-resistant clones and isolates from various geographical locations confirmed our initial observations with a chloroquine-resistant P. falciparum clone, W2. Fluoxetine concentrations of 500 nM were found to effectively modulate chloroquine resistance by 66% in clone W2. In comparison, verapamil at similar concentrations was observed to modulate chloroquine resistance in clone W2 by 61%. Neither fluoxetine nor verapamil was observed to possess any innate antimalarial activity. These data augment the current description of the chloroquine resistance phenotype and may provide additional insights into lead-directed synthesis of new antimalarial drugs.

Chloroquine-resistant Plasmodium falciparum accumulate significantly less chloroquine than susceptible parasites, and this is thought to be the basis of their resistance. However, the reason for the lower accumulation of chloroquine was unknown. The resistant parasite has now been found to release chloroquine 40 to 50 times more rapidly than the susceptible parasite, although their initial rates of chloroquine accumulation are the same. Verapamil and two other calcium channel blockers, as well as vinblastine and daunomycin, each slowed the release and increased the accumulation of chloroquine by resistant (but not susceptible) Plasmodium falciparum. These results suggest that a higher rate of chloroquine release explains the lower chloroquine accumulation, and thus the resistance observed in resistant Plasmodium falciparum.

Desipramine and several other tricyclic antidepressant drugs reverse chloroquine resistance in Plasmodium falciparum in vitro at concentrations observed in the plasma of human patients treated for depression. Reversal of resistance is associated with increased chloroquine accumulation in the parasite, probably because of inhibition of a putative chloroquine efflux pump. When owl monkeys (Aotus lemurinus lemurinus) infected with chloroquine-resistant Plasmodium falciparum were treated with chloroquine plus desipramine, their parasitemias were rapidly suppressed. Desipramine was found to be one of the most effective compounds yet described for the reversal of chloroquine resistance both in vitro and in vivo.