Key Points: In P falciparum–infected anemic children, immature gametocytes are more prevalent and abundant in bone marrow than in peripheral blood. P falciparum–infected anemic children are gametocyte carriers that can potentially contribute to malaria transmission.

Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by WHO to prevent malaria in African pregnant women. The spread of SP parasite resistance has raised concerns regarding long-term use for IPT. Mefloquine (MQ) is the most promising of available alternatives to SP based on safety profile, long half-life, and high efficacy in Africa. We evaluated the safety and efficacy of MQ for IPTp compared to those of SP in HIV-negative women. A total of 4,749 pregnant women were enrolled in an open-label randomized clinical trial conducted in Benin, Gabon, Mozambique, and Tanzania comparing two-dose MQ or SP for IPTp and MQ tolerability of two different regimens. The study arms were: (1) SP, (2) single dose MQ (15 mg/kg), and (3) split-dose MQ in the context of long lasting insecticide treated nets. There was no difference on low birth weight prevalence (primary study outcome) between groups (360/2,778 [13.0%]) for MQ group and 177/1,398 (12.7%) for SP group; risk ratio [RR], 1.02 (95% CI 0.86–1.22; p = 0.80 in the ITT analysis). Women receiving MQ had reduced risks of parasitemia (63/1,372 [4.6%] in the SP group and 88/2,737 [3.2%] in the MQ group; RR, 0.70 [95% CI 0.51–0.96]; p = 0.03) and anemia at delivery (609/1,380 [44.1%] in the SP group and 1,110/2743 [40.5%] in the MQ group; RR, 0.92 [95% CI 0.85–0.99]; p = 0.03), and reduced incidence of clinical malaria (96/551.8 malaria episodes person/year [PYAR] in the SP group and 130/1,103.2 episodes PYAR in the MQ group; RR, 0.67 [95% CI 0.52–0.88]; p = 0.004) and all-cause outpatient attendances during pregnancy (850/557.8 outpatients visits PYAR in the SP group and 1,480/1,110.1 visits PYAR in the MQ group; RR, 0.86 [0.78–0.95]; p = 0.003). There were no differences in the prevalence of placental infection and adverse pregnancy outcomes between groups. Tolerability was poorer in the two MQ groups compared to SP. The most frequently reported related adverse events were dizziness (ranging from 33.9% to 35.5% after dose 1; and 16.0% to 20.8% after dose 2) and vomiting (30.2% to 31.7%, after dose 1 and 15.3% to 17.4% after dose 2) with similar proportions in the full and split MQ arms. The open-label design is a limitation of the study that affects mainly the safety assessment. Women taking MQ IPTp (15 mg/kg) in the context of long lasting insecticide treated nets had similar prevalence rates of low birth weight as those taking SP IPTp. MQ recipients had less clinical malaria than SP recipients, and the pregnancy outcomes and safety profile were similar. MQ had poorer tolerability even when splitting the dose over two days. These results do not support a change in the current IPTp policy. ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001429343 Please see later in the article for the Editors' Summary Half the world's population is at risk of malaria, a mosquito-borne parasitic disease that kills about 600,000 people every year. Most of these deaths occur among young children in sub-Saharan Africa but pregnant women and their unborn children living in Africa are also very vulnerable to malaria. Infection with malaria during pregnancy can cause severe maternal anemia (reduced red blood cell numbers), stillbirths, and pre-term and low-birthweight babies, and is responsible for the deaths of many African babies and women. To prevent this loss of life, the World Health Organization (WHO) recommends a three-pronged approach—the delivery to pregnant women of the antimalarial drug sulfadoxine-pyrimethamine (SP) at each scheduled antenatal care visit given at least one month apart (intermittent preventive treatment in pregnancy; IPTp), the use of insecticide treated bed nets to protect pregnant women from the bites of infected mosquitoes, and effective case management of pregnant women with malarial illness. IPTp with SP reduces the delivery of low-birth-weight babies and neonatal deaths but malaria parasites are becoming resistant to SP. Thus, other antimalarial drugs need to be evaluated for use in IPTp. Suitable drugs need to remain in the body for a long time to maximize their prophylactic (preventative) effect, they need to be given as a single dose at antenatal clinic visits to ensure compliance, and they must not harm the unborn child. In this open-label, randomized controlled trial (RCT), the researchers compare the efficacy and safety of IPTp with SP and mefloquine (MQ, an antimalarial drug that matches these criteria) in HIV-negative women living in Africa. The study also compares the tolerability of two MQ regimens. RCTs compare outcomes in groups of people chosen to receive different interventions through the play of chance; in open-label RCTs, both the researchers and the study participants know which treatment is being administered. IPTp with SP is only recommended for HIV-negative women because SP interacts with cotrimoxazole, which is routinely given to HIV-positive individuals to prevent infections. The researchers assigned 4,749 pregnant women in Benin, Gabon, Mozambique, and Tanzania to one of three study groups. Participants in the SP and MQ groups received two doses of SP or MQ, respectively, administered at least one month apart. Participants in the split-dose MQ group received each MQ dose as half doses given on consecutive days. The prevalence of low-birth-weight deliveries (the study's primary outcome; the prevalence of a condition is the proportion of a population with that condition) was similar in the SP group and in the combined MQ groups. However, compared to women who received SP, women who received MQ had a lower risk of parasitemia (parasites in the blood), a lower risk of anemia at delivery, fewer episodes of clinical malaria, and fewer outpatient attendances. The prevalence of placental infection with malaria parasites and of adverse pregnancy outcomes such as stillbirth was similar in all the study groups. Finally, the tolerability of IPTp was poorer in the two MQ intervention groups than in the SP group, but similar proportions of adverse events (mainly dizziness and vomiting) were reported for the two MQ dosing regimens. These findings indicate that HIV-negative African women taking MQ for IPTp had a similar risk of a low-birth-weight delivery (the study's primary outcome) and lower risk of malaria illness during pregnancy than women taking SP for IPTp. Because the study did not have a no-IPTp arm (for ethical reasons), these findings provide no information about the efficacy or safety or either MQ or SP per se; these findings only indicate that MQ is no more efficacious than SP in the prevention of low-birth-weight babies. Moreover, because the study was open-label, the accuracy of the findings related to the tolerability and safety of MQ compared to SP may be limited because of biases in the assessment of safety outcomes. Given that the MQ dose used here for IPTp was associated with poorer tolerability than that of SP, these findings do not support the use of MQ instead of SP for IPTp. Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001733.

Current recommendations to prevent malaria in African pregnant women rely on insecticide treated nets (ITNs) and intermittent preventive treatment (IPTp). However, there is no information on the safety and efficacy of their combined use. 1030 pregnant Mozambican women of all gravidities received a long-lasting ITN during antenatal clinic (ANC) visits and, irrespective of HIV status, were enrolled in a randomised, double blind, placebo-controlled trial, to assess the safety and efficacy of 2-dose sulphadoxine-pyrimethamine (SP). The main outcome was the reduction in low birth weight. Two-dose SP was safe and well tolerated, but was not associated with reductions in anaemia prevalence at delivery (RR, 0.92 [95% CI, 0.79–1.08]), low birth weight (RR, 0.99 [95% CI, 0.70–1.39]), or overall placental infection (p = 0.964). However, the SP group showed a 40% reduction (95% CI, 7.40–61.20]; p = 0.020) in the incidence of clinical malaria during pregnancy, and reductions in the prevalence of peripheral parasitaemia (7.10% vs 15.15%) (p<0.001), and of actively infected placentas (7.04% vs 13.60%) (p = 0.002). There was a reduction in severe anaemia at delivery of borderline statistical significance (p = 0.055). These effects were not modified by gravidity or HIV status. Reported ITN's use was more than 90% in both groups. Two-dose SP was associated with a reduction in some indicators, but these were not translated to significant improvement in other maternal or birth outcomes. The use of ITNs during pregnancy may reduce the need to administer IPTp. ITNs should be part of the ANC package in sub-Saharan Africa. ClinicalTrials.gov NCT00209781

Unraveling the long-term kinetics of antibodies to SARS-CoV-2 and the individual characteristics influencing it, including the impact of pre-existing antibodies to human coronaviruses causing common cold (HCoVs), is essential to understand protective immunity to COVID-19 and devise effective surveillance strategies. IgM, IgA and IgG levels against six SARS-CoV-2 antigens and the nucleocapsid antigen of the four HCoV (229E, NL63, OC43 and HKU1) were quantified by Luminex, and antibody neutralization capacity was assessed by flow cytometry, in a cohort of health care workers followed up to 7 months (N = 578). Seroprevalence increases over time from 13.5% (month 0) and 15.6% (month 1) to 16.4% (month 6). Levels of antibodies, including those with neutralizing capacity, are stable over time, except IgG to nucleocapsid antigen and IgM levels that wane. After the peak response, anti-spike antibody levels increase from ~150 days post-symptom onset in all individuals (73% for IgG), in the absence of any evidence of re-exposure. IgG and IgA to HCoV are significantly higher in asymptomatic than symptomatic seropositive individuals. Thus, pre-existing cross-reactive HCoVs antibodies could have a protective effect against SARS-CoV-2 infection and COVID-19 disease.

Maternal mortality is a major health problem concentrated in resource-poor regions. Accurate data on its causes using rigorous methods is lacking, but is essential to guide policy-makers and health professionals to reduce this intolerable burden. The aim of this study was to accurately describe the causes of maternal death in order to contribute to its reduction, in one of the regions of the world with the highest maternal mortality ratios. We conducted a prospective study between October 2002 and December 2004 on the causes of maternal death in a tertiary-level referral hospital in Maputo, Mozambique, using complete autopsies with histological examination. HIV detection was done by virologic and serologic tests, and malaria was diagnosed by histological and parasitological examination. During 26 mo there were 179 maternal deaths, of which 139 (77.6%) had a complete autopsy and formed the basis of this analysis. Of those with test results, 65 women (52.8%) were HIV-positive. Obstetric complications accounted for 38.2% of deaths; haemorrhage was the most frequent cause (16.6%). Nonobstetric conditions accounted for 56.1% of deaths; HIV/AIDS, pyogenic bronchopneumonia, severe malaria, and pyogenic meningitis were the most common causes (12.9%, 12.2%, 10.1% and 7.2% respectively). Mycobacterial infection was found in 12 (8.6%) maternal deaths. In this tertiary hospital in Mozambique, infectious diseases accounted for at least half of all maternal deaths, even though effective treatment is available for the four leading causes, HIV/AIDS, pyogenic bronchopneumonia, severe malaria, and pyogenic meningitis. These observations highlight the need to implement effective and available prevention tools, such as intermittent preventive treatment and insecticide-treated bed-nets for malaria, antiretroviral drugs for HIV/AIDS, or vaccines and effective antibiotics for pneumococcal and meningococcal diseases. Deaths due to obstetric causes represent a failure of health-care systems and require urgent improvement.