Vaccins et traitements de la pandémie à Coronavirus SARS-CoV-2 : évidences scientifiques, dangers et essais cliniques: Vaccines and treatments for the Coronavirus SARS-CoV-2 pandemic: scientific evidence, dangers, and clinical trials

Since December 2019, an emerging disease due to Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) and called coronavirus (COVID-19), has spread quickly around the world from Wuhan, China; leading to an ever-increasing number of confirmed cases and deaths. Unfortunately, to date no drug or vaccine has yet been approved or recommended universally; current therapies are essentially supportive or compassionate. Several options are being considered or under study, including vaccines, antibiotics (azithromycin), antiviral agents (lopinavir, ritonavir, ribavirin, arbidol), anti-parasitic agents (chloroquin, hydroxychloroquin, ivermectin), immunomodulators and other molecules of the immune system (tocilizumab, interferons) and traditional medicine plants. Depuis décembre 2019, une maladie émergente à coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV) appelée coronavirus disease 2019 (COVID-19) s’est rapidement propagée dans le monde entier à partir de Wuhan en Chine, entrainant un nombre toujours plus élevé de cas confirmés et des décès. Malheureusement, à ce jour aucun médicament ou vaccin n’a encore été approuvé ou recommandé universellement, les thérapeutiques actuelles sont essentiellement de soutien ou compassionnelles. Plusieurs options sont envisagées ou en étude comprenant les vaccins, les antibiotiques (azithromycine), les agents antiviraux (lopinavir, ritonavir, Ribavirin, Arbidol), antiparasitaires (chloroquine, hydroxychloroquine, ivermectine), les immunomodulateurs et autres molécules du système immunitaire (Tocilizumab, interférons), les plantes de la médecine traditionnelle. &nbsp

Identification of the PfK13 mutations R561H and P441L in Democratic Republic of Congo (DRC).

BACKGROUND: Partial artemisinin resistance, mediated by P. falciparum K13 (PfK13) mutations, has been confirmed in certain areas of East Africa which are historically associated with high-level antimalarial resistance. DRC borders these areas in the East. OBJECTIVES: To determine the prevalence of resistance markers in six national malaria control programme (NMCP) surveillance sites; Boende, Kabondo, Kapolowe, Kimpese, Mikalayi and Rutshuru. METHODS: The SNPs in P. falciparum genes PfK13, Pfdhfr, Pfdhps, Pfmdr1 and Pfcrt were assessed using targeted NGS of isolates collected at enrolment in therapeutic efficacy studies. RESULTS: PfK13 SNPs were detected in two samples; in Kabondo (R561H) and in Rutshuru (P441L), both areas near Uganda and Rwanda. The Pfdhps ISGEGA haplotype, associated with reduced SP chemoprevention efficacy, ranged from 0.8% in Mikalayi (central DRC) to 42.2% in Rutshuru (East DRC). CONCLUSIONS: R561H and P441L observed in eastern DRC are a concern, as they are associated with delayed ACT-clearance and candidate marker of resistance, respectively. This is consistent with previous observations of shared drug resistance profiles in parasites of that region with bordering areas of Rwanda and Uganda. The likely circulation of parasites has important implications for the ongoing surveillance of partial artemisinin-resistant P. falciparum and for future efforts to mitigate its dispersal

Therapeutic Efficacy of Artemisinin-Based Combination Therapies in Democratic Republic of the Congo and Investigation of Molecular Markers of Antimalarial Resistance

Routine assessment of the efficacy of artemisinin-based combination therapies (ACTs) is critical for the early detection of antimalarial resistance. We evaluated the efficacy of ACTs recommended for treatment of uncomplicated malaria in five sites in Democratic Republic of the Congo (DRC): artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), and dihydroartemisinin-piperaquine (DP). Children aged 6–59 months with confirmed Plasmodium falciparum malaria were treated with one of the three ACTs and monitored. The primary endpoints were uncorrected and polymerase chain reaction (PCR)-corrected 28-day (AL and ASAQ) or 42-day (DP) cumulative efficacy. Molecular markers of resistance were investigated. Across the sites, uncorrected efficacy estimates ranged from 63% to 88% for AL, 73% to 100% for ASAQ, and 56% to 91% for DP. PCR-corrected efficacy estimates ranged from 86% to 98% for AL, 91% to 100% for ASAQ, and 84% to 100% for DP. No pfk13 mutations previously found to be associated with ACT resistance were observed. Statistically significant associations were found between certain pfmdr1 and pfcrt genotypes and treatment outcome. There is evidence of efficacy below the 90% cutoff recommended by WHO to consider a change in first-line treatment recommendations of two ACTs in one site not far from a monitoring site in Angola that has shown similar reduced efficacy for AL. Confirmation of these findings in future therapeutic efficacy monitoring in DRC is warranted

Drug-induced hepatotoxicity and association with slow acetylation variants NAT2*5 and NAT2*6 in Cameroonian patients with tuberculosis and HIV co-infection

Abstract Background Human immunodeficiency virus (HIV) and tuberculosis (TB) are major contributors to morbidity and mortality in sub-Saharan Africa including Cameroon. Pharmacogenetic variants could serve as predictors of drug-induced hepatotoxicity (DIH), in patients with TB co-infected with HIV. We evaluated the occurrence of DIH and pharmacogenetic variants in Cameroonian patients. Methods Treatment-naïve patients with HIV, TB or TB/HIV co-infection were recruited at three hospitals in Cameroon, between September 2018 and November 2019. Appropriate treatment was initiated, and patients followed up for 12 weeks to assess DIH. Pharmacogenetic variants were assessed by allele discrimination TaqMan SNP assays. Results Of the 141 treatment naïve patients, the overall incidence of DIH was 38% (53/141). The highest incidence of DIH, 52% (32/61), was observed among HIV patients. Of 32 pharmacogenetic variants, the slow acetylation variants NAT2*5 was associated with a decreased risk of DIH (OR: 0.4; 95%CI: 0.17–0.96; p = 0.038), while NAT2*6 was found to be associated with an increased risk of DIH (OR: 4.2; 95%CI: 1.1–15.2; p = 0.017) among patients treated for TB. Up to 15 SNPs differed in ≥ 5% of allele frequencies among African populations, while 25 SNPs differed in ≥ 5% of the allele frequencies among non-African populations, respectively. Conclusions DIH is an important clinical problem in African patients with TB and HIV. The NAT2*5 and NAT2*6 variants were found to be associated with DIH in the Cameroonian population. Prior screening for the slow acetylation variants NAT2*5 and NAT2*6 may prevent DIH in TB and HIV-coinfected patients

Plasmodium falciparum kelch 13 Mutations, 9 Countries in Africa, 2014–2018

The spread of drug resistance to antimalarial treatments poses a serious public health risk globally. To combat this risk, molecular surveillance of drug resistance is imperative. We report the prevalence of mutations in the Plasmodium falciparum kelch 13 propeller domain associated with partial artemisinin resistance, which we determined by using Sanger sequencing samples from patients enrolled in therapeutic efficacy studies from 9 sub-Saharan countries during 2014–2018. Of the 2,865 samples successfully sequenced before treatment (day of enrollment) and on the day of treatment failure, 29 (1.0%) samples contained 11 unique nonsynonymous mutations and 83 (2.9%) samples contained 27 unique synonymous mutations. Two samples from Kenya contained the S522C mutation, which has been associated with delayed parasite clearance; however, no samples contained validated or candidate artemisinin-resistance mutations