Assessing the therapeutic efficacy of artemether-lumefantrine for uncomplicated malaria in Lagos, Nigeria: a comprehensive study on treatment response and resistance markers.

BACKGROUND: The burden of malaria persists in sub-Saharan Africa and the emergence of artemisinin resistance has introduced complexity to control efforts. Monitoring the efficacy of artemisinin-based treatment for malaria is crucial to address this challenge. This study assessed treatment efficacy of artemether-lumefantrine (AL) and genetic diversity of Plasmodium falciparum isolates in a Nigerian population. METHODS: Participants presenting with clinical symptoms of uncomplicated malaria at a health centre in Lagos, Nigeria, were screened for P. falciparum. Enrolled participants were treated with AL and monitored through scheduled check-up visits, clinical and laboratory examinations for 28 days. Parasite clearance and genetic diversity were assessed through polymerase chain reaction (PCR) analysis of merozoite surface proteins (msp1 and msp2). The prevalence of drug resistance mutations was assessed by P. falciparum multidrug resistance gene 1 (mdr1) genotyping followed by P. falciparum ubiquitin-specific protease 1 (ubp1) gene sequencing. RESULTS: The PCR-uncorrected treatment outcome revealed 94.4% adequate clinical and parasitological response (ACPR) and 5.6% late parasitological failure (LPF) rates. After PCR correction, no suspected LPF case was detected and ACPR 67/67 (100%) was achieved in all the individuals. Moreover, a high prevalence of wild-type alleles for mdr1 N86Y (93.7%), and mdr1 D1246Y (87.5%) was observed. Genetic diversity analysis revealed predominant K1 allelic family for msp1 (90.2%) and FC27 for msp2 (64.4%). Estimated multiplicity of infection (MOI) was 1.7, with the highest MOI observed in the 5-15 years age group. ubp1 sequence analysis identified one nonsynonymous E1528D polymorphism at a low frequency (1.6%). CONCLUSION: The study demonstrated sustained efficacy of AL for treating uncomplicated P. falciparum malaria. Genetic diversity analysis revealed various allelic types, suggesting occurrences of polyclonal infections. Nonetheless, the detection of a significant ubp1 polymorphism could have future implications for the epidemiology of anti-malarial drug resistance in the population.

Challenges in conducting population-based seroepidemiology survey of COVID-19 in Lagos State, Nigeria.

Population-based study is known to be a very essential type of study during and after a pandemic or epidemic, as it provides crucial information on the incidence, prevalence, and risk factors of the disease in question. There has been limited information about the challenges faced in conducting such surveys in Nigeria. In this paper, we will share our experience, and describe the challenges faced in conducting a population-based seroepidemiological study of COVID-19 in Lagos, Nigeria. Some challenges were peculiar to specific Local Government Areas (LGAs) while others were general. The challenges include general misconceptions of community members about health research, difficulties in mapping houses, planning for data collection, standardizing data collection, working in hard-to-reach communities when resources were limited as well as difficulty in collection of blood and naso-oropharyngeal swabs. Ways of overcoming these problems, lessons learnt, and recommendations are hereby discussed.

The effects of cannabidiol on behavioural and oxidative stress parameters induced by prolonged haloperidol administration.

OBJECTIVES: We investigated the influence of oral cannabidiol (CBD) on vacuous chewing movements (VCM) and oxidative stress parameters induced by short- and long-term administration of haloperidol in a rat model of tardive dyskinesia (TD). METHODS: Haloperidol was administered either sub-chronically via the intraperitoneal (IP) route or chronically via the intramuscular (IM) route to six experimental groups only or in combination with CBD. VCM and oxidative stress parameters were assessed at different time points after the last dose of medication. RESULTS: Oral CBD (5 mg/kg) attenuated the VCM produced by sub-chronic administration of haloperidol (5 mg/kg) but had minimal effects on the VCM produced by chronic administration of haloperidol (50 mg/kg). In both sub-chronic and chronic haloperidol groups, there were significant changes in brain antioxidant parameters compared with CBD only and the control groups. The sub-chronic haloperidol-only group had lower glutathione activity compared with sub-chronic haloperidol before CBD and the control groups; also, superoxide dismutase, catalase, and 2,2-diphenyl-1-picrylhydrazyl activities were increased in the sub-chronic (IP) haloperidol only group compared with the CBD only and control groups. Nitric oxide activity was increased in sub-chronic haloperidol-only group compared to the other groups; however, the chronic haloperidol group had increased malondialdehyde activity compared to the other groups. CONCLUSIONS: Our findings indicate that CBD ameliorated VCM in the sub-chronic haloperidol group before CBD, but marginally in the chronic haloperidol group before CBD. There was increased antioxidant activity in the sub-chronic group compared to the chronic group.

A barcode of multilocus nuclear DNA identifies genetic relatedness in pre- and post-Artemether/Lumefantrine treated Plasmodium falciparum in Nigeria.

BACKGROUND: The decline in the efficacy of artemisinin-based combination treatment (ACT) in some endemic regions threatens the progress towards global elimination of malaria. Molecular surveillance of drug resistance in malaria-endemic regions is vital to detect the emergence and spread of mutant strains. METHODS: We observed 89 malaria patients for the efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum infections in Lagos, Nigeria and determined the prevalence of drug resistant strains in the population. Parasite clearance rates were determined by microscopy and the highly sensitive var gene acidic terminal sequence (varATS) polymerase chain reaction for 65 patients with samples on days 0, 1, 3, 7, 14, 21 and 28 after commencement of treatment. The genomic finger print of parasite DNA from pre- and post-treatment samples were determined using 24 nuclear single nucleotide polymorphisms (SNP) barcode for P. falciparum. Drug resistance associated alleles in chloroquine resistance transporter gene (crt-76), multidrug resistance genes (mdr1-86 and mdr1-184), dihydropteroate synthase (dhps-540), dihydrofolate reductase (dhfr-108) and kelch domain (K-13580) were genotyped by high resolution melt analysis of polymerase chain reaction (PCR) fragments. RESULTS: By varATS qPCR, 12 (18.5%) of the participants had detectable parasite DNA in their blood three days after treatment, while eight (12.3%) individuals presented with genotypable day 28 parasitaemia. Complexity of infection (CoI) was 1.30 on day 0 and 1.34 on day 28, the mean expected heterozygosity (HE) values across all barcodes were 0.50 ± 0.05 and 0.56 ± 0.05 on days 0 and 28 respectively. Barcode (π) pairwise comparisons showed high genetic relatedness of day 0 and day 28 parasite isolates in three (37.5%) of the eight individuals who presented with re-appearing infections. Crt-76 mutant allele was present in 38 (58.5%) isolates. The mdr1-86 mutant allele was found in 56 (86.2%) isolates. No mutation in the K-13580 was observed. CONCLUSIONS: Persistence of DNA-detectable parasitaemia in more than 18% of cases after treatment and indications of genetic relatedness between pre- and post-treatment infections warrants further investigation of a larger population for signs of reduced ACT efficacy in Nigeria.

Machine Learning-Based Hyperglycemia Prediction: Enhancing Risk Assessment in a Cohort of Undiagnosed Individuals.

Background: Noncommunicable diseases continue to pose a substantial health challenge globally, with hyperglycemia serving as a prominent indicator of diabetes. Objective: This study employed machine learning algorithms to predict hyperglycemia in a cohort of individuals who were asymptomatic and unraveled crucial predictors contributing to early risk identification. Methods: This dataset included an extensive array of clinical and demographic data obtained from 195 adults who were asymptomatic and residing in a suburban community in Nigeria. The study conducted a thorough comparison of multiple machine learning algorithms to ascertain the most effective model for predicting hyperglycemia. Moreover, we explored feature importance to pinpoint correlates of high blood glucose levels within the cohort. Results: Elevated blood pressure and prehypertension were recorded in 8 (4.1%) and 18 (9.2%) of the 195 participants, respectively. A total of 41 (21%) participants presented with hypertension, of which 34 (83%) were female. However, sex adjustment showed that 34 of 118 (28.8%) female participants and 7 of 77 (9%) male participants had hypertension. Age-based analysis revealed an inverse relationship between normotension and age (r=-0.88; P=.02). Conversely, hypertension increased with age (r=0.53; P=.27), peaking between 50-59 years. Of the 195 participants, isolated systolic hypertension and isolated diastolic hypertension were recorded in 16 (8.2%) and 15 (7.7%) participants, respectively, with female participants recording a higher prevalence of isolated systolic hypertension (11/16, 69%) and male participants reporting a higher prevalence of isolated diastolic hypertension (11/15, 73%). Following class rebalancing, the random forest classifier gave the best performance (accuracy score 0.89; receiver operating characteristic-area under the curve score 0.89; F1-score 0.89) of the 26 model classifiers. The feature selection model identified uric acid and age as important variables associated with hyperglycemia. Conclusions: The random forest classifier identified significant clinical correlates associated with hyperglycemia, offering valuable insights for the early detection of diabetes and informing the design and deployment of therapeutic interventions. However, to achieve a more comprehensive understanding of each feature's contribution to blood glucose levels, modeling additional relevant clinical features in larger datasets could be beneficial.

Perception, knowledge, and consumption pattern of dietary supplement used during COVID-19 pandemic among black Africans: Perspective of Nigerians.

The awareness of the health implication of Covid-19 pandemic marked an increase consumption of various dietary and herbal supplements (DHS) for the deterrence and/or prophylaxis against the novel emerging and infectious disease. However, there is little indication of the usefulness or otherwise of their use in alleviating symptoms of COVID-19. Objectives: To investigate the pattern and determinants of DHS use among the Nigerian population for the prevention and treatment of COVID-19. Design: Cross-sectional questionnaire survey. Setting: Older adolescents and adults residing in Nigeria. Participants: Participants (n = 645) residing in the Nigeria were recruited from different geo-political zones and various ethnic groups. Primary and secondary outcomes: Prevalence and determinants for the use of different DHS for the prevention and treatment of COVID-19 in Nigeria, and sources of information for DHS use. Results: Most participants (425, 65.9%) believed that dietary supplements are necessary during infectious disease outbreak, but a fewer proportion believed that supplements can be used in conjunction with other drugs to treat Covid-19. Vitamin C was the most known (70.0%) and Vitamin A. The least known (0.3%) dietary supplement Approximately half (50.2%) of the study subjects, more than a third (37.8%) and less than a quarter (22.7%) were aware that Folic acid, vitamin D and vitamin E are DS. Herbal dietary supplements mentioned as known by the study participants included Garlic (46.5%), Ginger (44.7%), Tumeric (36.3%), Moringa (40.0%) and Ginseng (26.3%). Citrus fruit as a DS was recognized by fewer (6.5%) study participants and only 1.6% referred to herbal tea as DHS. In all, 571 (88.5%) of the study participants took DHS during the Covid-19 pandemic with males 1.5 times more likely to take DHS than females (χ2 = 3.09, P-value = 0.08, OR = 1.54, 95% CI = 0.95, 2.47) during the pandemic. Participants reported lesser consumption of Selenium (27, 4.2%), Iron (20,3.1%), Zinc (61, 9.5%) and calcium (101, 15.7%) to prevent/treat Covid-19. Majority (271, 42.0%) of the study participants mentioned "health worker" as source of information on DHS while 13% mentioned "Social media". The sociodemographic determinants of DHS practices used to prevent/treat COVID-19 during the pandemic included older age group of 61-70 years, widows, secondary level of education and not employed. Conclusions: The findings showed widespread use of DHS for the prevention and treatment of COVID-19. The use of DHS in this study was mainly guided by health workers with a marginal role of social media and Mass media. These findings call for a more robust consolidative tactic towards DHS to ensure its proper and safe use.

Acute and subacute oral toxicity characterization and safety assessment of COVID organics® (Madagascar's Anti-COVID Herbal Tea) in animal models.

Introduction: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. No drug has been generally approved as safe and effective for the treatment of COVID-19. Several therapeutic agents such as COVID Organics® (CVO) have been explored as treatment options. CVO is an herbal tea composed of 62% of Artemisia annua and 38% of other plants. There is presently no existing scientific report and data on the safety and efficacy of CVO herbal drug. Thus, acute and subacute toxicity studies were undertaken to evaluate the safety and toxicity of CVO on short- and long-term usage in animal models. Materials and Methods: Phytochemical and nutritional compositions of CVO were determined using standard methods. Acute oral toxicity was investigated using female Swiss albino mice (three per group). While subacute oral toxicity was done using female and male Swiss albino rats (five per group). The animals were administered 2000 mg/kg, 5000 mg/kg, therapeutic dose; 5500 mg/kg and supratherapeutic dose; 11,000 mg/kg of CVO herbal product. The control group received water ad libitum. The oral toxicity studies were done in accordance with Organization for Economic Corporation and Development guidelines. The experimental protocol was approved by the Institutional Animal Care and Use Committee, Nigerian Institute of Medical Research (Ethics No. IRB/17/043). Results: CVO is rich in antioxidants: flavonoids (10.3%), tannins (29.1%), and phenolics (434.4 mg). It contains proteins (33.8%), carbohydrates (34.5%), fat (6.8%), and fiber (0.5%). In the acute toxicity study, no mortality was recorded in all the treated and untreated groups. The lethal dose of CVO is >5000 mg/kg body weight. The hematological, biochemical, lipid profile, and histologic parameters were all normal at therapeutic doses when compared to the control group. Conclusion: The acute and subacute oral toxicity studies revealed that CVO is not toxic. The specific organ toxicity evaluations also indicated that CVO has no toxic effects on blood parameters and vital organs structure and function at therapeutic dose. Thus, CVO is safe for short- and long-term usage. We recommend that CVO should be subjected to efficacy studies to investigate whether it is effective for COVID-19 treatment as claimed by the manufacturer.

Résumé Introduction: La maladie à coronavirus 2019 (COVID-19) est une maladie infectieuse causée par le coronavirus 2 du syndrome respiratoire aigu sévère. Aucun ne médicamenta été généralement approuvé comme étant sûr et efficace pour le traitement du COVID-19. Plusieurs agents thérapeutiques comme le COVID Organics® (CVO) ont été explorées comme options de traitement. CVO est une tisane composée à 62% d'Artemisia annua et à 38% d'autres plantes. Il y a actuellement il n'existe aucun rapport scientifique ni aucune donnée sur l'innocuité et l'efficacité du médicament à base de plantes CVO. Ainsi, des études de toxicité aiguë et subaiguë ont été entreprises évaluer la sécurité et la toxicité du CVO sur une utilisation à court et à long terme dans des modèles animaux. Matériels et méthodes: phytochimiques et les compositions nutritionnelles du CVO ont été déterminées à l'aide de méthodes standard. La toxicité orale aiguë a été étudiée chez des femmes albinos suisses souris (trois par groupe). La toxicité orale subaiguë a été réalisée sur des rats albinos suisses femelles et mâles (cinq par groupe). Les animaux étaient administrés 2 000 mg/kg, 5 000 mg/kg, 5 500 mg/kg (dose thérapeutique) et 11 000 mg/kg (dose suprathérapeutique) de produit à base de plantes CVO. Le le groupe témoin a reçu de l'eau à volonté. Les études de toxicité orale ont été réalisées conformément à l'Organisation pour la société économique et Directives de développement. Le protocole expérimental a été approuvé par le Comité institutionnel de protection et d'utilisation des animaux de l'Institut nigérian de Recherche médicale (Éthique n° IRB/17/043). Résultats: Le CVO est riche en antioxydants : flavonoïdes (10,3 %), tanins (29,1 %) et phénoliques (434,4 mg). Il contient des protéines (33,8 %), des glucides (34,5 %), des lipides (6,8 %) et des fibres (0,5 %). Dans l'étude de toxicité aiguë, aucune mortalité n'a été enregistrée chez tous les groupes traités et non traités. La dose mortelle de CVO est > 5 000 mg/kg de poids corporel. Le profil hématologique, biochimique, lipidique et les paramètres histologiques étaient tous normaux aux doses thérapeutiques par rapport au groupe témoin. Conclusion: Les conséquences orales aiguës et subaiguës des études de toxicité ont révélé que le CVO n'est pas toxique. Les évaluations de la toxicité spécifique pour certains organes ont également indiqué que le CVO n'a aucun effet toxique sur le sang. Paramètres et structure et fonction des organes vitaux à dose thérapeutique. Ainsi, CVO est sans danger pour une utilisation à court et à long terme. Nous recommandons que Le CVO doit être soumis à des études d'efficacité pour déterminer s'il est efficace pour le traitement du COVID-19, comme le prétend le fabricant. Mots-clés: Maladie à coronavirus 2019, plantes médicinales, histopathologie, produits phytochimiques, analyses immédiates, évaluation de la toxicité.

Contemporary Anti-Retroviral Drugs (ARVDs) Disrupt Follicular Development in Female Wistar Rats.

Introduction: There are genuine concerns that long-term use of anti-retroviral drugs may be associated with reproductive complications in females. This study aimed to ascertain the effect of highly active anti-retroviral drugs on the ovarian reserve and reproductive potential of female Wistar rats and by extension to HIV-positive human females. Methods: A total of 25 female Wistar rats, weighing between 140g and 162g, were randomly allotted into non-intervention and intervention groups, receiving the anti-retroviral drugs, Efavirenz (EFV), Tenofovir Disoproxil Fumarate (TDF), Lamivudine (3TC), and a fixed-dose combination (FDC). The dosage was administered orally at 8 am daily for 4 weeks. Serum concentrations of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinising hormone (LH), and estradiol were measured using standard biochemical techniques (ELISA). Follicular counts were made on fixed ovarian tissue from the sacrificed rats. Results: The mean AMH level for the control group and the EFV, TDF, 3TC, and FDC groups were 11.20, 6.75, 7.30, 8.27, and 6.60 pmol/L, respectively. The EFV and FDC groups had the lowest AMH, compared to the other groups, but there was no statistically significant difference in AMH across the groups. The mean count of antral follicles was significantly lower in the group that received EFV when compared to the other groups. The corpus luteal count was significantly higher in the control group than in the intervention groups. Conclusion: The study demonstrated a disruption in the reproductive hormones of female Wistar rats receiving anti-retroviral regimens containing EFV. Clinical studies are required to determine if these changes are seen in women receiving EFV-based treatment, as this may compromise reproductive function and predispose them to early menopause.

Design, Implementation, and Coordination of Malaria Therapeutic Efficacy Studies in Nigeria in 2018.

Prior to 2018, malaria therapeutic efficacy studies (TESs) in Nigeria were implemented separately at different sites, as assigned by the National Malaria Elimination Program (NMEP). In 2018, however, the NMEP engaged the Nigerian Institute of Medical Research to coordinate the 2018 TESs in 3 of 14 sentinel sites with the objective of standardizing their conduct across all three sites: Enugu, Kano, and Plateau states in three of six geopolitical zones. Artemether-lumefantrine and artesunate-amodiaquine, the two first-line drugs for treatment of acute uncomplicated malaria in Nigeria, were tested in both Kano and Plateau states. In Enugu State, however, artemether-lumefantrine and dihydroartemisinin-piperaquine were the test drugs, with dihydroartemisinin-piperaquine being tested for potential inclusion in Nigerian treatment policy. The TES was conducted in 6-month to 8-year-old children and was funded by the Global Fund with additional support from the WHO. A multipartite core team comprised of the NMEP, the WHO, the U.S. Presidential Malaria Initiative, academia, and the Nigerian Institute of Medical Research was set up to oversee the execution of the 2018 TES. This communication reports best practices adopted to guide its coordination, and lessons learned during in the process, including applying developed standard operating procedures, powering the sample size adequately for each site to report independently, training the investigating team for fieldwork, facilitating stratification of decisions, determining efficiencies derived from monitoring and quality assessment, and optimizing logistics. The planning and coordination of the 2018 TES activities is a model of a consultative process for the sustainability of antimalarial resistance surveillance in Nigeria.

A survey of chloroquine use for prevention and treatment of COVID-19 in Nigeria.

Background: Rampant chloroquine/hydroxychloroquine poisoning in Nigerian hospitals following suggestions of its possible efficacy in the treatment and prevention of the newly emerged COVID-19 disease informed this survey. Objectives: The aim of this study was to assess the knowledge, attitude and perception of the Nigerian populace on the use of chloroquine in the COVID-19 pandemic. Methods: This cross-sectional study was done by administering an electronic questionnaire created using Google Docs, through social media cascade methods including the WhatsApp application software to capture data on chloroquine use between April 20 and June 20, 2020. Results: Six hundred and twenty-eight people responded to the questionnaire (response rate 99.2%, mean age 41.05 ± 12.3) from the six geopolitical zones in Nigeria with 556 (88.5%) having tertiary level education. Only 21 (3.3%) of the respondents took chloroquine for treatment or prevention. Respondents from the North-west geopolitical zones used chloroquine 5.8 (95% CI: 1.55, 21.52, p=0.02) more times than other zones while the age group 20-29 were 8.8 times more likely to use chloroquine than any other age group (95% CI: 3.53, 21.70, p = 0.00). Female respondents were 2.3 times more likely to use chloroquine than the males (OR 2.26 95% CI: 0.90-5.68; p=0.08) and those in the income bracket of N75,000-99,000, 2.5 times more than other income groups. Conclusion: Young adults, North-western geopolitical zone, and female gender should be target groups for education on rational chloroquine use. The danger of chloroquine overdose should be communicated to the general population in Nigeria.

Effects of cannabidiol on vacuous chewing movements, plasma glucose and oxidative stress indices in rats administered high dose risperidone.

Atypical antipsychotics, despite their rapid dissociation from dopamine receptors and reduced tendency to induce oxidative stress, have been associated with difficult-to-manage movement disorders, including tardive dyskinesia (TD). The study set out to investigate the effects of cannabidiol (CBD), a potent antioxidant, on risperidone-induced behavioural and motor disturbances; namely vacuous chewing movements (VCM), and oxidative stress markers (e.g. superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), malondialdehyde (MDA), Nitric oxide (NO), and DPPH (2,2-diphenyl-1-picrylhydrazyl)). Oral risperidone (10 mg/kg) or oral CBD (5 mg/kg) were administered to six experimental groups. While risperidone alone was administered for 28 days, CBD concomitantly or in sequential order with risperidone, was administered for 28 days; and CBD alone was administered for 21 days. Behavioural, motor, and specific biochemical parameters, which included VCM, muscle tone, fasting blood sugar (FBS), and oxidative stress markers were assessed at different time points after the last dose of medication. Oral CBD (5 mg/kg) significantly reduced risperidone-induced elevated FBS when given after the administration of risperidone. Oral CBD also had effects on VCM when administered before risperidone and similarly, attenuated risperidone-induced increased muscle tone. It was also established that concomitant or sequential administration of CBD and risperidone did not have any adverse effects on cognition or locomotion. Both CBD and risperidone increased the activity of antioxidant enzymes and decreased the activity of pro-oxidant enzymes. This study suggests CBD could mitigate metabolic dysregulation and extrapyramidal side effects associated with risperidone without producing cognitive impairments.

Effects of cannabidiol on weight and fasting blood sugar with chronic and subchronic haloperidol administration.

OBJECTIVES: The duration of administration (e.g., subchronic or chronic) of haloperidol may influence its adverse effects. We studied the effects of duration of administration of haloperidol on body weight and fasting blood sugar (FBS). In addition, we examined whether orally administered cannabidiol (CBD) had any putative mitigating influence on haloperidol-induced body weight changes and FBS elevation. METHODS: Haloperidol (5 mg/kg/day) was administered for 21 days (subchronic administration), via the intraperitoneal (IP) route, or monthly (50 mg/kg monthly) for 3 months (chronic administration), via the intramuscular (IM) route, either alone or before CBD (5 mg/kg/day). Oral CBD (5 mg/kg/day) alone and distilled water alone were administered for 21 days. Weight and FBS were measured before administration of pharmacological agents (distilled water in the control group) and post-administration. RESULTS: Group differences in average weight across time were significant. Pairwise comparisons showed that mean weight of the subchronic (IP) haloperidol alone group (Group A) and the chronic (IM) haloperidol before CBD group (Group F) increased significantly over time. Post medications, there was a significant increase in mean FBS in the subchronic (IP) haloperidol group compared to the subchronic (IP) haloperidol before CBD group. There was also a significant reduction in mean FBS from the baseline for the control group only. CONCLUSION: We demonstrated that the duration of administration of haloperidol influenced weight and FBS in rats, suggesting that metabolic side effects, may be influenced by duration of administration. CBD ameliorated the increase in weight and FBS observed in the subchronic (IP) haloperidol groups.

Molecular docking, simulation and binding free energy analysis of small molecules as PfHT1 inhibitors.

Antimalarial drug resistance has thrown a spanner in the works of malaria elimination. New drugs are required for ancillary support of existing malaria control efforts. Plasmodium falciparum requires host glucose for survival and proliferation. On this basis, P. falciparum hexose transporter 1 (PfHT1) protein involved in hexose permeation is considered a potential drug target. In this study, we tested the antimalarial activity of some compounds against PfHT1 using computational techniques. We performed high throughput virtual screening of 21,352 small-molecule compounds against PfHT1. The stability of the lead compound complexes was evaluated via molecular dynamics (MD) simulation for 100 nanoseconds. We also investigated the pharmacodynamic, pharmacokinetic and physiological characteristics of the compounds in accordance with Lipinksi rules for drug-likeness to bind and inhibit PfHT1. Molecular docking and free binding energy analyses were carried out using Molecular Mechanics with Generalized Born and Surface Area (MMGBSA) solvation to determine the selectivity of the hit compounds for PfHT1 over the human glucose transporter (hGLUT1) orthologue. Five important PfHT1 inhibitors were identified: Hyperoside (CID5281643); avicularin (CID5490064); sylibin (CID5213); harpagoside (CID5481542) and quercetagetin (CID5281680). The compounds formed intermolecular interaction with the binding pocket of the PfHT1 target via conserved amino acid residues (Val314, Gly183, Thr49, Asn52, Gly183, Ser315, Ser317, and Asn48). The MMGBSA analysis of the complexes yielded high free binding energies. Four (CID5281643, CID5490064, CID5213, and CID5481542) of the identified compounds were found to be stable within the PfHT1 binding pocket throughout the 100 nanoseconds simulation run time. The four compounds demonstrated higher affinity for PfHT1 than the human major glucose transporter (hGLUT1). This investigation demonstrates the inhibition potential of sylibin, hyperoside, harpagoside, and avicularin against PfHT1 receptor. Robust preclinical investigations are required to validate the chemotherapeutic properties of the identified compounds.

Mutations in Pfcrt and Pfmdr1 genes of Plasmodium falciparum isolates from two sites in Northcentral and Southwest Nigeria.

The ability of malaria parasites to develop resistance to antimalarial drugs has made it necessary to continuously survey malaria parasite populations for resistance markers. Mutations in specific malaria parasite genes confer resistance to antimalarial drugs. The study compared mutations in Pfcrt and Pfmdr1 genes of P. falciparum from two ecologically different areas of Nigeria. Plasmodium falciparum dried blood spots collected from New Bussa (Northcentral Nigeria) and Ijede (Southwest Nigeria) were analysed by PCR-RFLP for Pfcrt, K76 T, Pfmdr1, N86Y and Y184F mutations. Pfmdr1 copy number was determined by quantitative-PCR. A total of 145 blood spots [Ijede = 55; New Bussa = 90 blood spots] were analysed, but Pfcrt gene was successfully amplified in 144 samples while Pfmdr1 was amplified in 132 samples. Overall, prevalence of mutant forms of Pfcrt 76 T,Pfmdr1 86Y and 184F were 74.3% (95% CI: 66.4-81.2%), 18.2% (95% CI: 12.0-25.8%) and 35.6% (95% CI: 27.5-44.4%). The frequency of Pfcrt 76 T was similar in both study sites [Ijede: 81.8% (95%CI: 69.1-90.9%); New Bussa: 69.7% (95%CI: 59.0-79.0), p = 0.105]. However, the frequencies of Pfmdr1 86Y and 184F were significantly higher in Ijede (28.3% and 62.3%) than in New Bussa (11.4% and 17.7%), respectively (P < 0.05). Eight parasite genotypes based on three codons of the two genes were identified. The most frequent genotype was TNY 53(40.5%) while the least was KYF 1 (0.8%). The most frequent genotype in Ijede and New Bussa were TNF 18(34.0%) and TNY 40 (51.3%) respectively. The frequency of wild strain KNF in Ijede and New Bussa were 3 (5.7%) and 18 (23.1%), respectively. The distribution of the genotypes differed significantly by location. The genotypes with more than two or more mutations were more in Ijede 32 (60.4%) than in New Bussa 16 (20.5%) (p < 0.001). Amplification of Pfmdr1 copy number was not observed in the two study sites. The prevalence of Pfcrt 76 T was similar in both locations while Pfmdr1 86Y and 184F differed in both locations. Single nucleotide polymorphisms in the three codons assessed were more in Ijede than in New Bussa.

Mucoadhesive Microspheres of Maraviroc and Tenofovir Designed for Pre-Exposure Prophylaxis of HIV-1: An in vitro Assessment of the Effect on Vaginal Lactic Acid Bacteria Microflora.

PURPOSE: To formulate and evaluate microspheres of the antiretroviral drugs maraviroc and tenofovir intended for a candidate vaginal microbicide and assess its effect on the vaginal lactic acid bacteria microflora. METHODS: Ionic gelation technique was used to formulate maraviroc and tenofovir microspheres with subsequent characterization. The effect of varying concentrations of the polymer, crosslinking agent and the curing time on the outcome variables viz: particle size, mucoadhesion and encapsulation efficiency were investigated. Lactic acid bacteria were isolated from the vagina of healthy women using standard microbiologic methods. The analysis of their 16S rRNA sequence data identified Lactobacillus fermentum and Enterococcus faecalis strains which were assigned GenBank accession numbers. The efficacy of the microspheres on HIV-1BaL strain was evaluated using TZM-bl indicator cells. RESULTS: The optimal maraviroc and tenofovir microspheres had particle sizes of (434.82 µm and 456.18 µm), mucoadhesion of (93.3% and 90%) and encapsulation efficiency (92.80% and 78.9%) respectively. Maraviroc release kinetics followed a zero-order model and tenofovir was released via Higuchi model. The assay of a 1 mg/mL suspension of the microspheres on the strains of Lactobacillus fermentum and Enterococcus faecalis showed a viability of 93.9% and 89.7%, respectively. There was a statistically significant difference between the mean absorbance readings of the test agent and that of the positive control (P = 0.001). The microspheres elicited a progressive decline in HIV infectivity until at a concentration of 1 µg/mL. CONCLUSION: The antiretroviral drugs loaded in the microspheres, had good mucoadhesion which is a potential for prolonged residence time in the vagina. The antiretroviral drugs were adequately released from the microspheres and showed efficacy against the HIV-1 BaL virus strain. There was no significant disruption in the growth of the lactic acid bacteria which constitute valuable bacteria microflora of the vagina.

Self-reported use of and access to personal protective equipment among healthcare workers during the COVID-19 outbreak in Nigeria.

The SARS-CoV-2 virus is highly infectious resulting in increased infection and death among the front-line Healthcare Workers (HCW) because of limited access to personal protective equipment (PPE). This study assesses the availability and self-reported use of PPE amongst HCW during the COVID-19 pandemic in Nigeria. A mixed-method study was conducted through a cross-sectional survey and in-depth interviews amongst HCW. Quantitative data analysis was done using SPSS version 26 and thematic analysis was done for the in-depth interview. A total of 258 HCW completed the survey while 15 HCW took part in the in-depth interview. The mean age was 40 (±8.6) years, 67.4% were female and 83.3% were married. 49% were Doctors, 21.1% were Nurses, 28.7% were other allied HCW and 62.2% had at least 10 years of practice experience. Only 22.1% of HCWs had regular access to PPE and only 20.6% had access to N-95 facemask compare to other PPEs. Male HCWs and those working at secondary or tertiary facilities had access to N-95 facemask (p-value 0.025 and 0.010 respectively). The facilitator of PPE use is leadership quality of hospital head and donation of PPE to the facilities while the barriers to PPE use include a limited supply of PPE, as well as facility's infrastructural and operational challenges. The study reported limited access to essential PPE with varying perspectives on its use. Therefore, access, knowledge, and appropriate use of PPE need urgent attention with improved implementation of infection control policy at the facility level.

Investigation of the effects of cannabidiol on vacuous chewing movements, locomotion, oxidative stress and blood glucose in rats treated with oral haloperidol.

Objectives: Tardive dyskinesia (TD) unlike acute dystonia may be irreversible. This study investigated the effects of oral cannabidiol (CBD) on haloperidol-induced vacuous chewing movement (VCM) model of TD. Methods: There were six experimental groups with different combinations of oral cannabidiol with 5 mg/kg of haloperidol given orally. Behavioural assays and FBS were measured. VCMs were assessed after the last dose of medication. Blood for oxidative stress assays was collected on the 8th day after the administration of the last dose of medication. Results: This study found that CBD co-administration with haloperidol attenuated the VCMs and increased motor tone produced by haloperidol. CBD alone at 5 mg/kg appears to have anxiolytic properties but may not be as effective as haloperidol which exhibited a greater anxiolytic effect at 5 mg/kg. Treatment with CBD alone at 5 mg/kg also appeared to enhance brain DPPH scavenging activity. Conclusions: We confirmed that CBD can ameliorate motor impairments produced by haloperidol. Our data suggest that CBD can be combined with haloperidol to prevent the emergent of extrapyramidal side effects and long-term movement disorders, such as acute dystonic disorder and TD.

Implementation of a modified drive-through sampling strategy for SARS-CoV-2-the Nigerian experience.

INTRODUCTION: effective and safe means of sample collection is a crucial component of testing for Covid-19. Uptake of testing is key to containing and controlling the spread of the virus. Scientists have been working on various strategies that will increase the uptake of testing for COVID-19. One such method involves the use of the drive-through sampling strategy. METHODS: data was collected by both qualitative and quantitative methods. An eligibility form was filled online. While in-depth interviews were conducted for the qualitative aspect of the study. RESULTS: 2,600 visits were recorded at the website, 2300 (88.46%) participants successfully registered for the test. 57.4% were found eligible of which 78.0% presented for the test. This Consisted of 78.0% drive-through and 22.0% walk-in. The average time for transiting through the drive-through site was 19.2 ± 4.6minutes while that of the walk-in was 28 ± 9.2min. This difference was statistically significant (p<0.001). In the qualitative component, respondents opined that maximum safety measures were deployed to protect both participants and health workers. Most said that the turnaround time for the sampling process was short. CONCLUSION: the sampling strategy although largely successful, is largely dependent on Internet penetrability, thus this sampling modality will be best utilized as an adjunct to established models of sample collection.

Acute and subacute oral toxicity characterization and safety assessment of COVID organics® (Madagascar's Anti­COVID Herbal Tea) in animal models

Introduction: Coronavirus disease 2019 (COVID 19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. No drug has been generally approved as safe and effective for the treatment of COVID 19. Several therapeutic agents such as COVID Organics® (CVO) have been explored as treatment options. CVO is an herbal tea composed of 62% of Artemisia annua and 38% of other plants. There is presently no existing scientific report and data on the safety and efficacy of CVO herbal drug. Thus, acute and subacute toxicity studies were undertaken to evaluate the safety and toxicity of CVO on short and long term usage in animal models. Materials and Methods: Phytochemical and nutritional compositions of CVO were determined using standard methods. Acute oral toxicity was investigated using female Swiss albino mice (three per group). While subacute oral toxicity was done using female and male Swiss albino rats (five per group). The animals were administered 2000 mg/kg, 5000 mg/kg, therapeutic dose; 5500 mg/kg and supratherapeutic dose; 11,000 mg/kg of CVO herbal product. The control group received water ad libitum. The oral toxicity studies were done in accordance with Organization for Economic Corporation and Development guidelines. The experimental protocol was approved by the Institutional Animal Care and Use Committee, Nigerian Institute of Medical Research (Ethics No. IRB/17/043). Results: CVO is rich in antioxidants: flavonoids(10.3%), tannins(29.1%), and phenolics(434.4 mg). It contains proteins (33.8%), carbohydrates (34.5%), fat (6.8%), and fiber (0.5%). In the acute toxicity study, no mortality was recorded in all the treated and untreated groups. The lethal dose of CVO is >5000 mg/kg body weight. The hematological, biochemical, lipid profile, and histologic parameters were all normal at therapeutic doses when compared to the control group. Conclusion: The acute and subacute oral toxicity studies revealed that CVO is not toxic. The specific organ toxicity evaluations also indicated that CVO has no toxic effects on blood parameters and vital organs structure and function at therapeutic dose. Thus, CVO is safe for short and long term usage. We recommend that CVO should be subjected to efficacy studies to investigate whether it is effective for COVID 19 treatment as claimed by the manufacturer.

Knowledge, attitude and practice on malaria prevention and sulfadoxine-pyrimethamine utilisation among pregnant women in Badagry, Lagos State, Nigeria.

Background: Malaria in pregnancy is one of the major causes of mater nal morbidity and mortality as well as of poor pregnancy outcomes. We studied the knowledge, attitude and practices of pregnant women on malaria prevention, assessed their knowledge of sulfadoxine-pyrimethamine (SP) for intermittent preventive therapy in pregnancy (IPTp-SP), and used the outcomes to create awareness on malaria prevention with IPTp-SP. Materials and methods: A structured questionnaire on malaria prevention and SP utilisation was administer ed to 450 pregnant women attending antenatal clinics in both government and private health facilities in Badagry, Lagos State, Nigeria. Results: 355 (78.8% ) of the pregnant women perceived malaria as a serious illness. Other responses by the respondents included: parasitic disease (13; 2.9%); caused by mosquito (5; 1.9%), while 77 (17%) said they did not know. The signs and symptoms of malaria mentioned included headache (109; 24.2%), weakness (77; 17.1%), fever (77; 17.1%) and body pains (44; 10%). 174 (58%) women indicated that they would go to a hospital when having malaria, 54 (17%) indulged in self-medication, while 32 (11%) took herbs. 43 (14%) did nothing. Malaria prevention was performed by taking herbs (134; 30%); artemisinin-based combination therapy (ACT) (123; 27%); daraprim (104; 23%); blood tonic (51; 11%); paracetamol (21; 5%) and SP (17; 4%). Mosquito control was mainly carried out by the use of insecticide spray (215; 47.7%), followed by anti-mosquito coils (95; 21%). Out of the 450 pregnant women interviewed, 350 (84.5%) said that SP was for the treatment of malaria, while 69 (15.2%) said that it was for malaria prevention. Knowledge of SP was influenced by both education (P<0.05) and parity (P<0.001). Conclusion: The majority of the pregnant women had knowledge of SP but did not know that it is used for malaria prevention. Most of the respondents took malaria-preventive measures by taking herbs but preferred to go to the hospital when suspecting that they had malaria.