Pregnancy outcomes and risk of placental malaria after artemisinin-based and quinine-based treatment for uncomplicated falciparum malaria in pregnancy: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis.

Malaria in pregnancy, including asymptomatic infection, has a detrimental impact on foetal development. Individual patient data (IPD) meta-analysis was conducted to compare the association between antimalarial treatments and adverse pregnancy outcomes, including placental malaria, accompanied with the gestational age at diagnosis of uncomplicated falciparum malaria infection. A systematic review and one-stage IPD meta-analysis of studies assessing the efficacy of artemisinin-based and quinine-based treatments for patent microscopic uncomplicated falciparum malaria infection (hereinafter uncomplicated falciparum malaria) in pregnancy was conducted. The risks of stillbirth (pregnancy loss at ≥ 28.0 weeks of gestation), moderate to late preterm birth (PTB, live birth between 32.0 and < 37.0 weeks), small for gestational age (SGA, birthweight of < 10th percentile), and placental malaria (defined as deposition of malaria pigment in the placenta with or without parasites) after different treatments of uncomplicated falciparum malaria were assessed by mixed-effects logistic regression, using artemether-lumefantrine, the most used antimalarial, as the reference standard. Registration PROSPERO: CRD42018104013. Of the 22 eligible studies (n = 5015), IPD from16 studies were shared, representing 95.0% (n = 4765) of the women enrolled in literature. Malaria treatment in this pooled analysis mostly occurred in the second (68.4%, 3064/4501) or third trimester (31.6%, 1421/4501), with gestational age confirmed by ultrasound in 91.5% (4120/4503). Quinine (n = 184) and five commonly used artemisinin-based combination therapies (ACTs) were included: artemether-lumefantrine (n = 1087), artesunate-amodiaquine (n = 775), artesunate-mefloquine (n = 965), and dihydroartemisinin-piperaquine (n = 837). The overall pooled proportion of stillbirth was 1.1% (84/4361), PTB 10.0% (619/4131), SGA 32.3% (1007/3707), and placental malaria 80.1% (2543/3035), and there were no significant differences of considered outcomes by ACT. Higher parasitaemia before treatment was associated with a higher risk of SGA (adjusted odds ratio [aOR] 1.14 per 10-fold increase, 95% confidence interval [CI] 1.03 to 1.26, p = 0.009) and deposition of malaria pigment in the placenta (aOR 1.67 per 10-fold increase, 95% CI 1.42 to 1.96, p < 0.001). The risks of stillbirth, PTB, SGA, and placental malaria were not different between the commonly used ACTs. The risk of SGA was high among pregnant women infected with falciparum malaria despite treatment with highly effective drugs. Reduction of malaria-associated adverse birth outcomes requires effective prevention in pregnant women

Antimicrobial Susceptibility of <em>Campylobacter</em> Strains Isolated from Chicken Carcasses in Senegal

Campylobacter resistance to antimicrobial agents appears as an emerging public health problem in industrialized countries, but, on the other hand, only few data on the subject are available in developing countries. To assess antibiotic susceptibility of Campylobacter strains in Senegal, skin samples were collected from 250 chicken carcasses from January 2001 to October 2002. Among 204 Campylobacter strains isolated, two species were identified: C. jejuni (59%) and C. coli (41%). In vitro susceptibility to five antimicrobial drugs (amoxicillin, amoxicillin-clavulanic acid, erythromycin, nalidixic acid and ciprofloxacin) was determined by the E-test method. Minimum inhibitory concentrations (MICs) showed 34% of Campylobacter isolates were ciprofloxacin resistant with a high level of resistance (MIC ≥ 32 mg/l) in 25% of both species. Cross-resistance between nalidixic acid and ciprofloxacin was found in 96% of quinolone-resistant strains. The level of amoxicillin resistance was statistically higher for C. coli than for C. jejuni (20.2 versus 10.8%), but all the strains were susceptible to amoxicillin combined with clavulanic acid. Both species showed low resistance to erythromycin. Multiresistant phenotype to three of the drugs tested was found in 9.8% of the strains: 15.5% of C. coli strains and 5.8% of C. jejuni strains. No strain was resistant to four or more of the drugs studied. Further studies appear necessary to evaluate antibiotic resistance of Campylobacter isolated in human and animal samples in order to control the emergence of new multidrug-resistant strains in Senegal

Systèmes d’aide à la décision clinique pour la pédiatrie en santé globale [Paediatric digital clinical decision support for global health]

Effective, scalable and sustainable strategies to improve quality of care are needed to address the substantial burden of preventable deaths of children under-five in resource-constrained settings. Clinical decision support systems (CDSS), digital tools which generate recommendations for healthcare providers based on patient-specific information, show promise. By strengthening adherence to evidence-based assessment, diagnosis and management and generating high-quality data, CDSS can improve quality care - care that is effective, safe, people-centered, timely, equitable, integrated and efficient. Designing and implementing CDSS that deliver this impact is a complex and iterative process. We advocate for collaboration on developing and evaluating these tools to guide their implementation for maximal impact

Efficacy and tolerability of artemisinin-based and quinine-based treatments for uncomplicated falciparum malaria in pregnancy: a systematic review and individual patient data meta-analysis.

Malaria in pregnancy affects both the mother and the fetus. However, evidence supporting treatment guidelines for uncomplicated (including asymptomatic) falciparum malaria in pregnant women is scarce and assessed in varied ways. We did a systematic literature review and individual patient data (IPD) meta-analysis to compare the efficacy and tolerability of different artemisinin-based or quinine-based treatments for malaria in pregnant women. We did a systematic review of interventional or observational cohort studies assessing the efficacy of artemisinin-based or quinine-based treatments in pregnancy. Seven databases (MEDLINE, Embase, Global Health, Cochrane Library, Scopus, Web of Science, and Literatura Latino Americana em Ciencias da Saude) and two clinical trial registries (International Clinical Trials Registry Platform and ClinicalTrials.gov) were searched. The final search was done on April 26, 2019. Studies that assessed PCR-corrected treatment efficacy in pregnancy with follow-up of 28 days or more were included. Investigators of identified studies were invited to share data from individual patients. The outcomes assessed included PCR-corrected efficacy, PCR-uncorrected efficacy, parasite clearance, fever clearance, gametocyte development, and acute adverse events. One-stage IPD meta-analysis using Cox and logistic regression with random-effects was done to estimate the risk factors associated with PCR-corrected treatment failure, using artemether-lumefantrine as the reference. This study is registered with PROSPERO, CRD42018104013. Of the 30 studies assessed, 19 were included, representing 92% of patients in the literature (4968 of 5360 episodes). Risk of PCR-corrected treatment failure was higher for the quinine monotherapy (n=244, adjusted hazard ratio [aHR] 6·11, 95% CI 2·57-14·54, p&lt;0·0001) but lower for artesunate-amodiaquine (n=840, 0·27, 95% 0·14-0·52, p&lt;0·0001), artesunate-mefloquine (n=1028, 0·56, 95% 0·34-0·94, p=0·03), and dihydroartemisinin-piperaquine (n=872, 0·35, 95% CI 0·18-0·68, p=0·002) than artemether-lumefantrine (n=1278) after adjustment for baseline asexual parasitaemia and parity. The risk of gametocyte carriage on day 7 was higher after quinine-based therapy than artemisinin-based treatment (adjusted odds ratio [OR] 7·38, 95% CI 2·29-23·82). Efficacy and tolerability of artemisinin-based combination therapies (ACTs) in pregnant women are better than quinine. The lower efficacy of artemether-lumefantrine compared with other ACTs might require dose optimisation. The Bill &amp; Melinda Gates Foundation, ExxonMobil Foundation, and the University of Oxford Clarendon Fund

Beneficial effects of low doses of red wine consumption on perturbed shear stress-induced atherogenesis

Moderate wine intake is associated with a reduced risk of morbidity and mortality from cardiovascular disease. Atherosclerosis is enhanced in arterial segments exposed to disturbed flow. Perturbed shear stress increases also the endothelial expression of oxidation-sensitive responsive genes (such as ELK-1 and p-JUN). This study evaluates the effects of chronic consumption of red wine on perturbed shear stress-induced atherogenesis. Results indicated that chronic treatment with red wine significantly attenuated the activation of redox-sensitive genes (ELK-1 and p-JUN) and increased endothelial nitric oxide synthase (eNOS) expression (which was decreased by perturbed shear stress) in cultured human coronary endothelial cells (EC) and in atherosclerosis-prone areas of hypercholesterolemic mice. Oral administration of red wine to hypercholesterolemic mice reduced significantly the progression of atherosclerosis. Moreover, short-term supplementation with red wine to C57BL/6J mice significantly increased upregulation of aortic eNOS and SIRT1 expression induced by physical training. These findings establish that administration of low doses of red wine can attenuate the proatherogenic effects induced by perturbed shear stress in vitro and in vivo. This evidence may have implications for the prevention of atherosclerotic lesion progression and its clinical manifestations