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Prevalence estimates of SARS-CoV-2 infection in Africa are limited, particularly among pregnant women and in those living with HIV. This study assessed the seroprevalence of SARS-CoV-2 antibodies among Mozambican HIV-infected pregnant women during the first year of the pandemic, before COVID-19 vaccines were deployed in the country.The study was conducted in Manhiça district, a semi-rural area in southern Mozambique.A prospective cohort study including pregnant women living with HIV was carried out from November 2019 to June 2021. Women were enrolled at the first antenatal care (ANC) clinic visit and followed until post-partum. HIV viral load (HIV-VL) and IgM/IgG antibodies against SARS-CoV-2 were determined in blood samples at first ANC clinic visit and at delivery. Associations between SARS-CoV-2 serostatus and maternal characteristics at enrolment were analysed.A total of 397 women were enrolled. SARS-CoV-2 IgG/IgM antibodies were detected in 7.1% of women at enrolment and in 8.5% of women at delivery. Overall, SARS-CoV-2 antibodies were detected in 45 (11.3%; 95%CI 8.4-14.9%) women during the study period; the first seropositive sample was identified in September 2020. Having undetectable HIV-VL was associated with seropositivity of SARS-CoV-2 IgG/IgM (OR 3.35 [1.10-11.29]; p=0.039).Seroprevalence of SARS-CoV-2 antibodies in this cohort of Mozambican unvaccinated pregnant women was similar to reported global estimates of approximately 10% in pregnancy for 2021. Findings also suggest that pregnant women with high HIV- viral load may have an impaired immune response against SARS-CoV-2 and might need to be carefully managed in case of COVID-19.

IntroductionMalaria infection during pregnancy is an important driver of maternal and neonatal health especially among HIV-infected women. Intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine–pyrimethamine is recommended for malaria prevention in HIV-uninfected women, but it is contraindicated in those HIV-infected on cotrimoxazole prophylaxis (CTXp) due to potential adverse effects. Dihydroartemisinin–piperaquine (DHA–PPQ) has been shown to improve antimalarial protection, constituting a promising IPTp candidate. This trial’s objective is to determine if monthly 3-day IPTp courses of DHA–PPQ added to daily CTXp are safe and superior to CTXp alone in decreasing the proportion of peripheral malaria parasitaemia at the end of pregnancy.Methods and analysisThis is a multicentre, two-arm, placebo-controlled, individually randomised trial in HIV-infected pregnant women receiving CTXp and antiretroviral treatment. A total of 664 women will be enrolled at the first antenatal care clinic visit in sites from Gabon and Mozambique. Participants will receive an insecticide-treated net, and they will be administered monthly IPTp with DHA-PPQ or placebo (1:1 ratio) as directly observed therapy from the second trimester of pregnancy. Primary study outcome is the prevalence of maternal parasitaemia at delivery. Secondary outcomes include prevalence of malaria-related maternal and infant outcomes and proportion of adverse perinatal outcomes. Participants will be followed until 6 weeks after the end of pregnancy and their infants until 1 year of age to also evaluate the impact of DHA–PPQ on mother-to-child transmission of HIV. The analysis will be done in the intention to treat and according to protocol cohorts, adjusted by gravidity, country, seasonality and other variables associated with malaria.Ethics and disseminationThe protocol was reviewed and approved by the institutional and national ethics committees of Gabon and Mozambique and the Hospital Clinic of Barcelona. Project results will be presented to all stakeholders and published in open-access journals.Trial registration numberNCT03671109.

Podeu consultar dades primàries associades a l'article a: http://hdl.handle.net/2445/111582, BACKGROUND: Despite that over 90 million pregnancies are at risk of Plasmodium vivax infection annually, little is known about the epidemiology and impact of the infection in pregnancy. METHODOLOGY AND PRINCIPAL FINDINGS: We undertook a health facility-based prospective observational study in pregnant women from Guatemala (GT), Colombia (CO), Brazil (BR), India (IN) and Papua New Guinea PNG). Malaria and anemia were determined during pregnancy and fetal outcomes assessed at delivery. A total of 9388 women were enrolled at antennal care (ANC), of whom 53% (4957) were followed until delivery. Prevalence of P. vivax monoinfection in maternal blood at delivery was 0.4% (20/4461) by microscopy [GT 0.1%, CO 0.5%, BR 0.1%, IN 0.2%, PNG 1.2%] and 7% (104/1488) by PCR. P. falciparum monoinfection was found in 0.5% (22/4463) of women by microscopy [GT 0%, CO 0.5%, BR 0%, IN 0%, PNG 2%]. P. vivax infection was observed in 0.4% (14/3725) of placentas examined by microscopy and in 3.7% (19/508) by PCR. P. vivax in newborn blood was detected in 0.02% (1/4302) of samples examined by microscopy [in cord blood; 0.05% (2/4040) by microscopy, and 2.6% (13/497) by PCR]. Clinical P. vivax infection was associated with increased risk of maternal anemia (Odds Ratio-OR, 5.48, [95% CI 1.83-16.41]; p = 0.009), while submicroscopic vivax infection was not associated with increased risk of moderate-severe anemia (Hb

Background The World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine‐pyrimethamine for malaria for all women who live in moderate to high malaria transmission areas in Africa. However, parasite resistance to sulfadoxine‐pyrimethamine has been increasing steadily in some areas of the region. Moreover, HIV‐infected women on cotrimoxazole prophylaxis cannot receive sulfadoxine‐pyrimethamine because of potential drug interactions. Thus, there is an urgent need to identify alternative drugs for prevention of malaria in pregnancy. One such candidate is mefloquine. Objectives To assess the effects of mefloquine for preventing malaria in pregnant women, specifically, to evaluate: • the efficacy, safety, and tolerability of mefloquine for preventing malaria in pregnant women; and • the impact of HIV status, gravidity, and use of insecticide‐treated nets on the effects of mefloquine. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, Latin American Caribbean Health Sciences Literature (LILACS), the Malaria in Pregnancy Library, and two trial registers up to 31 January 2018. In addition, we checked references and contacted study authors to identify additional studies, unpublished data, confidential reports, and raw data from published trials. Selection criteria Randomized and quasi‐randomized controlled trials comparing mefloquine IPT or mefloquine prophylaxis against placebo, no treatment, or an alternative drug regimen. Data collection and analysis Two review authors independently screened all records identified by the search strategy, applied inclusion criteria, assessed risk of bias, and extracted data. We contacted trial authors to ask for additional information when required. Dichotomous outcomes were compared using risk ratios (RRs), count outcomes as incidence rate ratios (IRRs), and continuous outcomes using mean differences (MDs). We have presented all measures of effect with 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach for the following main outcomes of analysis: maternal peripheral parasitaemia at delivery, clinical malaria episodes during pregnancy, placental malaria, maternal anaemia at delivery, low birth weight, spontaneous abortions and stillbirths, dizziness, and vomiting. Main results Six trials conducted between 1987 and 2013 from Thailand (1), Benin (3), Gabon (1), Tanzania (1), Mozambique (2), and Kenya (1) that included 8192 pregnant women met our inclusion criteria. Two trials (with 6350 HIV‐uninfected pregnant women) compared two IPTp doses of mefloquine with two IPTp doses of sulfadoxine‐pyrimethamine. Two other trials involving 1363 HIV‐infected women compared three IPTp doses of mefloquine plus cotrimoxazole with cotrimoxazole. One trial in 140 HIV‐infected women compared three doses of IPTp‐mefloquine with cotrimoxazole. Finally, one trial enrolling 339 of unknown HIV status compared mefloquine prophylaxis with placebo. Study participants included women of all gravidities and of all ages (four trials) or > 18 years (two trials). Gestational age at recruitment was > 20 weeks (one trial), between 16 and 28 weeks (three trials), or ≤ 28 weeks (two trials). Two of the six trials blinded participants and personnel, and only one had low risk of detection bias for safety outcomes. When compared with sulfadoxine‐pyrimethamine, IPTp‐mefloquine results in a 35% reduction in maternal peripheral parasitaemia at delivery (RR 0.65, 95% CI 0.48 to 0.86; 5455 participants, 2 studies; high‐certainty evidence) but may have little or no effect on placental malaria infections (RR 1.04, 95% CI 0.58 to 1.86; 4668 participants, 2 studies; low‐certainty evidence). Mefloquine results in little or no difference in the incidence of clinical malaria episodes during pregnancy (incidence rate ratio (IRR) 0.83, 95% CI 0.65 to 1.05, 2 studies; high‐certainty evidence). Mefloquine decreased maternal anaemia at delivery (RR 0.84, 95% CI 0.76 to 0.94; 5469 participants, 2 studies; moderate‐certainty evidence). Data show little or no difference in the proportions of low birth weight infants (RR 0.95, 95% CI 0.78 to 1.17; 5641 participants, 2 studies; high‐certainty evidence) and in stillbirth and spontaneous abortion rates (RR 1.20, 95% CI 0.91 to 1.58; 6219 participants, 2 studies; I2 statistic = 0%; moderate‐certainty evidence). IPTp‐mefloquine increased drug‐related vomiting (RR 4.76, 95% CI 4.13 to 5.49; 6272 participants, 2 studies; high‐certainty evidence) and dizziness (RR 4.21, 95% CI 3.36 to 5.27; participants = 6272, 2 studies; moderate‐certainty evidence). When compared with cotrimoxazole, IPTp‐mefloquine plus cotrimoxazole probably results in a 48% reduction in maternal peripheral parasitaemia at delivery (RR 0.52, 95% CI 0.30 to 0.93; 989 participants, 2 studies; moderate‐certainty evidence) and a 72% reduction in placental malaria (RR 0.28, 95% CI 0.14 to 0.57; 977 participants, 2 studies; moderate‐certainty evidence) but has little or no effect on the incidence of clinical malaria episodes during pregnancy (IRR 0.76, 95% CI 0.33 to 1.76, 1 study; high‐certainty evidence) and probably no effect on maternal anaemia at delivery (RR 0.94, 95% CI 0.73 to 1.20; 1197 participants, 2 studies; moderate‐certainty evidence), low birth weight rates (RR 1.20, 95% CI 0.89 to 1.60; 1220 participants, 2 studies; moderate‐certainty evidence), and rates of spontaneous abortion and stillbirth (RR 1.12, 95% CI 0.42 to 2.98; 1347 participants, 2 studies; very low‐certainty evidence). Mefloquine was associated with higher risks of drug‐related vomiting (RR 7.95, 95% CI 4.79 to 13.18; 1055 participants, one study; high‐certainty evidence) and dizziness (RR 3.94, 95% CI 2.85 to 5.46; 1055 participants, 1 study; high‐certainty evidence). Authors' conclusions Mefloquine was more efficacious than sulfadoxine‐pyrimethamine in HIV‐uninfected women or daily cotrimoxazole prophylaxis in HIV‐infected pregnant women for prevention of malaria infection and was associated with lower risk of maternal anaemia, no adverse effects on pregnancy outcomes (such as stillbirths and abortions), and no effects on low birth weight and prematurity. However, the high proportion of mefloquine‐related adverse events constitutes an important barrier to its effectiveness for malaria preventive treatment in pregnant women., Mefloquine for preventing malaria in pregnant women What is the aim of this review? The aim of this Cochrane Review was to find out whether the antimalarial drug mefloquine is efficacious and safe for prevention of malaria in pregnant women living in stable transmission areas. We found six relevant studies to help us answer this question. Key messages The antimalarial drug mefloquine is efficacious for malaria prevention in pregnant women. The drug has been found to be safe in terms of adverse pregnancy outcomes, such as low birth weight, prematurity, stillbirths and abortions, and congenital malformations. However, it is worse tolerated than other antimalarial drugs. What was studied in the review? Pregnant women are vulnerable to malaria infection, especially if they are living with HIV. The consequences of malaria during pregnancy can be severe and include poor health outcomes for both women and their children. For this reason, in malaria‐endemic areas of stable transmission, women are recommended to prevent malaria infection by sleeping under mosquito bed‐nets and by taking effective drugs (such as sulphadoxine‐pyrimethamine or cotrimoxazole in case of HIV infection) as chemoprevention against malaria throughout pregnancy. This Cochrane Review looked at the effects of mefloquine for prevention of malaria in both HIV‐uninfected and HIV‐infected pregnant women. What are the main results of the review? We found five relevant studies conducted in sub‐Saharan Africa and one in Thailand between 1987 and 2013. These studies compared mefloquine with placebo or other antimalarial drugs currently recommended for prevention of malaria in pregnant women. The review shows the following: • Compared with sulfadoxine‐pyrimethamine, mefloquine chemoprevention in HIV‐uninfected women: ◦reduces risks of maternal peripheral parasitaemia (presence of malaria parasites in the blood of women) and anaemia at delivery; ◦ makes no difference in the prevalence of adverse maternal outcomes (such as low birth weight, prematurity, stillbirths and abortions, and congenital malformations) and in the incidence of clinical malaria episodes during pregnancy; and ◦ increases risks of drug‐related adverse events including vomiting, fatigue/weakness, and dizziness. • Compared with cotrimoxale prophylaxis alone, mefloquine chemoprevention plus cotrimoxazole in HIV‐infected women: ◦ reduces the risk of maternal peripheral parasitaemia at delivery and the risk of placental malaria; ◦ makes no difference in the prevalence of adverse pregnancy outcomes (such as low birth weight, prematurity, stillbirths and abortions, and congenital malformations) and in the incidence of clinical malaria episodes during pregnancy; and ◦ increases the risk of drug‐related adverse events such as vomiting and dizziness. Overall, the high proportion of mefloquine‐related adverse events constitutes an important barrier to its effectiveness for malaria preventive treatment in pregnant women. How up‐to‐date is this review? The review authors searched for studies up to 31 January 2018.

The objective of this study was to analyse an array of ciprofloxacin and norfloxacin derivatives in order to determine those with good activity against bacteria that already present fluoroquinolone resistance associated with mutations in the gyrA and/or parC genes. Four norfloxacin and 20 ciprofloxacin derivatives were synthesised and tested against quinolone-susceptible and -resistant Escherichia coli, Acinetobacter baumannii, Stenotrophomonas maltophilia and Staphylococcus aureus strains using a microdilution test. Among the derivatives, the 4-methyl-7-piperazine ciprofloxacin derivative showed a minimum inhibitory concentration for 50% of the organisms that was 16- and 8-fold lower than ciprofloxacin for A. baumannii and S. maltophilia, respectively. When the methyl group at position 4 in the piperazine ring was substituted by ethyl, butyl or heptyl groups, activity against A. baumannii steadily decreased. The 7-(4-methyl)-piperazine ciprofloxacin derivative (UB-8902) showed very good activity against these multiresistant microorganisms including A. baumannii and S. maltophilia.

One of the goals of computational chemists is to automate the de novo design of bioactive molecules. Despite significant advances in computational approaches to ligand design and binding energy evaluation, novel procedures for ligand design are required. Evolutionary computation provides a new approach to this design endeavor. We propose an evolutionary tool for de novo peptide design, based on the evaluation of energies for peptide binding to a user-defined protein surface patch. Special emphasis has been placed on the evaluation of the proposed peptides, leading to two different evaluation heuristics. The software developed was successfully tested on the design of ligands for the proteins prolyl oligopeptidase, p53, and DNA gyrase.

Background Plasmodium vivax can potentially lead to life-threatening episodes but the mechanisms underlying severe disease remain poorly defined. Cytoadhesion of infected erythrocytes may contribute to P. vivax sequestration and organ injury although its physiological impact is still unknown. Here, we aimed to describe clinically-relevant cytoadhesive phenotypes of P. vivax isolates. Methodology/Principal findings Rosetting and adhesion to CSA, CD36, ICAM1, placental and brain cryosections were determined in P. vivax peripheral isolates from 12 pregnant women, 24 non-pregnant women and 23 men from Manaus (Brazil). P. falciparum co-infection was excluded by PCR and P. vivax isolates were genotyped by assessing the size polymorphism of microsatellites ms2, ms20 and msp1F3 through capillary electrophoresis of PCR products. P. vivax monoinfection was confirmed by PCR in 59 isolates, with 50 (85%) of them being single-clone infections. One P. vivax haplotype was more frequently found among pregnant women (33%) than in non-pregnant women (0%) and men (4%; p = 0.010). Rosetting was observed in 64% of the isolates, adhesion to CSA in 15%, to ICAM1 in 12% and to placental cryosections in 9%, being similar among pregnant and non-pregnant groups. Intensity of rosetting was higher among anaemic individuals compared to non-anaemic (p = 0.010) and decreased with increasing haematocrit (p = 0.033) and haemoglobin levels (p = 0.015). Conclusions/Significance P. vivax peripheral isolates from pregnant women do not exhibit a prominent adhesion to CSA, although other parasite phenotypes still unknown may increase the propagation of certain P. vivax clones observed among pregnant hosts. Rosetting is a frequent cytoadhesive phenotype in P. vivax infections that may contribute to the development of anaemia., Author Summary Despite being considered a relatively benign disease, Plasmodium vivax infection has been recently associated with fatal outcomes. The mechanisms contributing to severe disease in P. vivax malaria remain largely unknown, although scarce evidences suggests that similarly to P. falciparum, P. vivax may also adhere to host receptors on the vascular endothelium or on uninfected erythrocytes to form ‘rosettes’. Such cytoadhesion phenotypes might contribute to mild sequestration of P. vivax and poor clinical outcomes. The present study aimed to describe clinically relevant cytoadhesive phenotypes of P. vivax infected erythrocytes isolated from peripheral blood of pregnant and non-pregnant patients in the Brazilian Amazon. We did not observe any specific cytoadhesion phenotype associated to pregnancy, although a P. vivax haplotype was more frequent among pregnant women than in non-pregnant hosts. This finding suggests that other parasite phenotypes still unknown may increase the propagation of certain P. vivax clones among pregnant hosts. In addition, we found that rosetting was a frequent cytoadhesive phenotype in P. vivax infections that was associated with an increased risk of anaemia. This study places cytoadhesion and specifically rosetting as a target for the development of new therapies to treat or prevent life-threatening P. vivax malaria.

Plasmodium vivax is the most widely distributed human parasite and the main cause of human malaria outside the African continent. However, the knowledge about the genetic variability of P. vivax is limited when compared to the information available for P. falciparum. We present the results of a study aimed at characterizing the genetic structure of P. vivax populations obtained from pregnant women from different malaria endemic settings. Between June 2008 and October 2011 nearly 2000 pregnant women were recruited during routine antenatal care at each site and followed up until delivery. A capillary blood sample from the study participants was collected for genotyping at different time points. Seven P. vivax microsatellite markers were used for genotypic characterization on a total of 229 P. vivax isolates obtained from Brazil, Colombia, India and Papua New Guinea. In each population, the number of alleles per locus, the expected heterozygosity and the levels of multilocus linkage disequilibrium were assessed. The extent of genetic differentiation among populations was also estimated. Six microsatellite loci on 137 P. falciparum isolates from three countries were screened for comparison. The mean value of expected heterozygosity per country ranged from 0.839 to 0.874 for P. vivax and from 0.578 to 0.758 for P. falciparum. P. vivax populations were more diverse than those of P. falciparum. In some of the studied countries, the diversity of P. vivax population was very high compared to the respective level of endemicity. The level of inter-population differentiation was moderate to high in all P. vivax and P. falciparum populations studied.