• Effect of sex hormones on COVID-19 outcome bias in males and females. • Effect of immunological factors on COVID-19 outcome bias in males and females. • Angiotensin-converting enzyme-2 (ACE2) system and COVID-19 outcome in males and females. • Correlation between smoking and COVID-19 incidence in males and females. • Possible therapeutic options for COVID-19.

We describe the Pf8 data resource, the latest MalariaGEN release of curated genome variation data on over 33,000 Plasmodium falciparum samples from 99 partner studies and 122 locations over more than 50 years. This release provides open access to raw sequencing data and genotypes at over 12 million genomic positions. For the first time, it includes copy-number variation (CNV) calls in the drug-resistance associated genes gch1 and crt . As in Pf7, CNV calls are provided for mdr1 and plasmepsin2/3 , along with calls for deletion in hrp2 and hrp3, genes associated with rapid diagnostic test failures. This data resource additionally features derived datasets, interactive web applications for exploring patterns of drug resistance and variation in over 5,000 genes, an updated Python package providing methods for accessing and analysing the data, and open access analysis notebooks that can be used as starting points for further analyses. In addition, informative example analyses show contrasting profiles of the decline of chloroquine resistance-associated mutations in Africa, and variation in copy number variation across 10 distinct sub-populations. To the best of our knowledge, Pf8 is the largest open data set of genome variation in any eukaryotic species, making it an invaluable foundational resource for understanding evolution, including that of pathogens.

Background: The adulticidal and cercaricidal activities of five Ghanaian medicinal plants, namely, Phyllanthus amarus, Vernonia amygdalina, Azadirachta indica, Morinda lucida and Nauclea latifolia against S. mansoni were evaluated in this study. Six weeks old ICR mice (n = 25) were percutaneously infected with S. mansoni cercariae. Nine weeks later, infected mice (n = 5) were anaesthetised and perfused for adult S. mansoni. Cercariae were treated with different concentrations (1000, 500, 250, 125, 62.5, 31.25 μg/mL) of methanolic extracts of the experimenting plants in triplicates. Adult S. mansoni incopula were also treated with same concentrations of each extract or 20 μg/mL praziquantel. The cercariae and adult worms were observed at time intervals for 180 min and 120 h to assess mortality and viability respectively. Additionally, 9-week cercariae-infected mice (4 groups of 5 mice) were treated with either 500 mg/kg po A. indica or V. amygdalina, 400 mg/kg po praziquantel or distilled water for 14 days. The mice were euthanized after adult worms were recovered from them. The liver was processed and histologically examined for granuloma formations. Results: All the plants exhibited varying cercaricidal and adulticidal activities against S. mansoni in a time and concentration-dependent manner. A. indica (3 h IC₅₀ = 27.62 μg/mL) and V. amygdalina (3 h IC₅₀ = 35.84 μg/mL) exerted the highest cercaricidal activity. Worm recovery after treatment with V. amygdalina, A. indica and praziquantel in vivo was 48.8%, 85.1 % and 59.9 % respectively (p < 0.05). A. indica and V. amydalina-treated mice recorded lesser mean liver and spleen weights compared to untreated groups (p < 0.05). Conclusion: A. indica demonstrated the highest cercaricidal and alduticidal activities in vitro, whereas V. amygdalina exhibited the most potent aldulticidal activity in vivo. This study could provide baseline information which can be used to develop plant-based alternative commercial drugs against S. mansoni.

Background: Clinicians in areas where malaria and typhoid fever are co-endemic often treat infected patients irrationally, which may lead to the emergence of drug resistance and extra cost to patients. This study determined the proportion of febrile conditions attributable to either malaria and/or typhoid fever and the susceptibility patterns of Salmonella spp. isolates to commonly used antimicrobial agents in Ghana. Methods: One hundred and fifty-seven (157) febrile patients attending the Ga West Municipal Hospital, Ghana, from February to May 2017 were sampled. Blood samples were collected for cultivation of pathogenic bacteria and the susceptibility of the Salmonella isolates to antimicrobial agents was performed using the Kirby-Bauer disk diffusion method with antibiotic discs on Müller Hinton agar plates. For each sample, conventional Widal test for the detection of Salmonella spp was done as well as blood film preparation for detection of Plasmodium spp. Data on the socio-demographic and clinical characteristics of the study participants were collected using an android technology software kobo-collect by interview. Results: Of the total number of patients aged 2–37 years (median age = 6 years, IQR 3–11), 82 (52.2%) were females. The proportion of febrile patients with falciparum malaria was 57/157 (36.3%), while Salmonella typhi O and H antigens were detected in 23/157 (14.6%) of the samples. The detection rate of Salmonella spp in febrile patients was 10/157 (6.4%). Malaria and typhoid fever coinfection using Widal test and blood culture was 9 (5.7%) and 3 (1.9%), respectively. The isolates were highly susceptible to cefotaxime, ceftriaxone, ciprofloxacin, and amikacin but resistant to ampicillin, tetracycline, co-trimoxazole, gentamicin, cefuroxime, chloramphenicol, and meropenem. Conclusion: Plasmodium falciparum and Salmonella spp coinfections were only up to 1.9%, while malaria and typhoid fever, individually, were responsible for 36.3% and 6.4%, respectively. Treatment of febrile conditions must be based on laboratory findings in order not to expose patients to unnecessary side effects of antibiotics and reduce the emergence and spread of drug resistance against antibiotics.

Background: Plasmodium falciparum parasites, which could harbour anti-malaria drug resistance genes, are commonly detected in blood donors in malaria-endemic areas. Notwithstanding, anti-malaria drug resistant biomarkers have not been characterized in blood donors with asymptomatic P. falciparum infection. Methods: A total of 771 blood donors were selected from five districts in the Greater Accra Region, Ghana. Each donor sample was screened with malaria rapid diagnostic test (RDT) kit and parasitaemia quantified microscopically. Dried blood spots from malaria positive samples were genotyped for P. falciparum chloroquine resistance transporter (Pfcrt), P. falciparum multi-drug resistance (Pfmdr1), P. falciparum dihydropteroate-synthetase (Pfdhps), P. falciparum dihydrofolate-reductase (Pfdhfr) and Kelch 13 propeller domain on chromosome 13 (Kelch 13) genes. Results: Of the 771 blood donors, 91 (11.8%) were positive by RDT. Analysis of sequence reads indicated successful genotyping of Pfcrt, Pfmdr1, Pfdhfr, Pfdhps and Kelch 13 genes in 84.6, 81.3, 86.8, 86.9 and 92.3% of the isolates respectively. Overall, 21 different mutant haplotypes were identified in 69 isolates (75.8%). In Pfcrt, CVIET haplotype was observed in 11.6% samples while in Pfmdr1, triple mutation (resulting in YFN haplotype) was detected in 8.1% of isolates. In Pfdhfr gene, triple mutation resulting in IRNI haplotype and in Pfdhps gene, quintuple mutation resulting in AGESS haplotype was identified in 17.7% parasite isolates. Finally, five non-synonymous Kelch 13 alleles were detected; C580Y (3.6%), P615L (4.8%), A578S (4.8%), I543V (2.4%) and A676S (1.2%) were detected. Conclusion: Results obtained in this study indicated various frequencies of mutant alleles in Pfcrt, Pfmdr1, Pfdhfr, Pfdhps and Kelch 13 genes from P. falciparum infected blood donors. These alleles could reduce the efficacy of standard malaria treatment in transfusion-transmitted malaria cases. Incorporating malaria screening into donor screening protocol to defer infected donors is therefore recommended.

In sub-Saharan Africa where sickle cell trait (SCT) and malaria is prevalent, significant proportions of blood donors may be affected by one or more of these abnormalities. The haemato-biochemical properties of SCT and asymptomatic malaria in donor blood have not been evaluated. This study evaluated the haemato-biochemical impact of SCT and asymptomatic malaria infections in citrate-phosphate-dextrose-adenine (CPDA-1) stored donor blood units. Fifty-milliliters of sterile CPDA-1 anti-coagulated blood were drained into the sample pouch attached to the main blood bag. Ten units each of sickle cell/malaria negative, sickle cell and malaria positive blood were analyzed. Baseline and weekly haematological profiling and week 1, 3 and 5 concentrations of plasma haemoglobin, % haemolysis, sodium, potassium and chloride and lactate dehydrogenase (LDH) were assayed. Differences between baseline and weekly data were determined using one-way analysis of variance (ANOVA) and Kruskal-Wallis test, whereas differences between baseline parameters and week 1–3 data pairs were determined using paired t-test. P-value < 0.05 was considered statistically significant. Storage of SCT and malaria infected blood affected all haematological cell lines. In the SCT donors, red blood cells (RBC) (4.75 × 10¹²/L ± 1.43^baseline to 3.49 × 10¹²/L ± 1.09^week-5), haemoglobin (14.45 g/dl ± 1.63^baseline to 11.43 g/dl ± 1.69^week-5) and haematocrit (39.96% ± 3.18^baseline to 33.22% ± 4.12^week-5) were reduced. In the asymptomatic malaria group, reductions were observed in RBC (5.00 × 10¹²/L ± 0.75^baseline to 3.72 × 10¹²/L ± 0.71^week-5), haemoglobin (14.73 g/dl ± 1.67^baseline to 11.53 g/dl ± 1.62^week-5), haematocrit (42.72% ± 5.16^baseline to 33.38% ± 5.80^week-5), mean cell haemoglobin concentration (35.48 g/dl ± 1.84^baseline to 35.01 g/dl ± 0.64^week-5) and red cell distribution width coefficient of variation (14.81% ± 1.54^baseline to 16.26% ± 1.37^week-5). Biochemically, whereas plasma LDH levels significantly increased in asymptomatic malaria blood donors (319% increase at week 5 compared to baseline), SCT blood donors had the most significant increase in plasma potassium levels at week 5 (382% increase). Sodium ions significantly reduced in SCT/malaria negative and sickle cell trait blood at an average rate of 0.21 mmol/L per day. Moreover, elevations in lymphocytes-to-eosinophils and lymphocytes-to-neutrophils ratios were associated with SCT and malaria positive blood whilst elevation lymphocytes-to-basophils ratio was exclusive to malaria positive blood. Severe storage lesions were significant in SCT or malaria positive donor blood units. Proper clinical evaluation must be done in prospective blood donors to ensure deferral of such donors.