Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Molecular epidemiology of drug-resistant Plasmodium falciparum in Benguela province, Angola

Background: The malaria situation has been worsening in Angola, partly due to armed conflict until the recent past and drug-resistant Plasmodium falciparum. Malaria transmission is heterogeneous within the country, and data on drug-resistant malaria in different parts of the country are incomplete. The aim of the present study was to evaluate resistance to 4-aminoquinolines and antifolate drugs in P. falciparum isolates collected in Benguela province, central Angola, using molecular markers. Methods: Fingerprick capillary blood was collected from asymptomatic children aged less than 15 years old during a household survey in and around Balombo town in 2010-2011. Samples were screened for P. falciparum by nested PCR. Molecular markers (P. falciparum dihydrofolate reductase [pfdhfr], P. falciparum dihydropteroate synthase [pfdhps], P. falciparum chloroquine resistance transporter [pfcrt], and P. falciparum multidrug-resistance gene 1 [pfmdr1]) were sequenced to determine the key codons associated with drug resistance. Results: A total of 60 blood samples were positive for P. falciparum. Most isolates with successful PCR amplification had mutant pfdhfr alleles, with either double mutant AICNI (69%) or triple mutant AIRNI (21%) haplotypes. A16V, S108T, and I164L substitutions were not found. Many of the isolates were carriers of either SGKAA (60%) or AGKAA (27%) pfdhps haplotype. K540E substitution was absent. There were only two pfcrt haplotypes: wild-type CVMNK (11%) and mutant CVIET (89%). Wild-type pfmdr1 NYSND haplotype was found in 19% of the isolates, whereas single mutant pfmdr1 YYSND and NFSND haplotypes occurred in 48% and 11%, respectively. Double mutant pfmdr1 haplotypes (YFSND and YYSNY) occurred rarely. Conclusions: The results suggest that the high prevalence of mutant pfcrt CVIET haplotype is in agreement with low clinical efficacy of chloroquine observed in earlier studies and that the double pfdhfr mutant AICNI and single pfdhps mutant SGKAA are currently the predominant haplotypes associated with antifolate resistance in Benguela province. The hallmark of clinical resistance observed in East Africa, i.e. triple pfdhfr mutant haplotype (AIRNI) and double pfdhps mutant haplotype (SGEAA), was absent. These molecular findings need to be further evaluated in parallel with clinical studies, in particular with the efficacy of intermittent preventive treatment using sulphadoxine-pyrimethamine in pregnant women and artesunate-amodiaquine for uncomplicated malaria

A review of Cameroonian medicinal plants with potentials for the management of the COVID-19 pandemic

Since the outbreak in December 2019, in Wuhan (China) of COVID-19, approved drugs are still lacking and the world is seeking effective treatment. The purpose of this article is to review the medicinal plants with potential to be used as complementary therapies against COVID-19. Bibliographic information was searched in several databases (Google Scholar, PubMed, Scopus, ScienceDirect, PROTA, ResearchGate and GLOBEinMED), to retrieve relevant papers on (1) plants used to manage common symptoms of COVID-19, (2) plant secondary metabolites with confirmed inhibitory effects on COVID-19 and (3) plants exhibiting pharmacological activities of relevance for COVID-19 management. A total of 230 species was recorded as potential source of ingredients for the fight against the 2019 novel corona virus. Of these species, 30 contain confirmed antiCOVID-19 secondary metabolites, 90 are used traditionally to manage at least 3 common symptoms of COVID-19, 10 have immunostimulant activity, 52 have anti-inflamatory activity, 14 have antiviral properties and 78 species are documented as used to treat malaria. A PCA analysis showing cluster formatting among the recorded species indicates 4 groups of species and an array of possibility of using individual species or a combination of species for their complementary effects. The authors argue that Cameroonian medicinal plants can be of potential contribution to the fight against COVID-19. Further applied research is needed to provide more scientific evidence for their efficacy, to establish standard formulations and clinical studies as part of efforts to develop therapies for COVID-19