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Abstract Background Eotaxin-1 concentrations in plasma have been inversely associated with malaria exposure, malaria infection and pregnancy, but the effect of these conditions on the levels of the related chemokines eotaxin-2 and eotaxin-3 remains unknown. Methods Eotaxin-2 and -3 concentrations were measured in 310 peripheral or placental plasma samples from pregnant and non-pregnant individuals from Papua New Guinea (malaria-endemic country) and Spain (malaria-naïve individuals) with previous data on eotaxin-1 concentrations. Correlations between eotaxin concentrations were examined with the Spearman’s test. Differences in eotaxin concentrations among groups were evaluated with the Kruskal–Wallis or Mann Whitney tests. The pairwise Wilcoxon test was performed to compare eotaxin-2 concentration between peripheral and placental matched plasmas. Univariable and multivariable linear regression models were estimated to assess the association between eotaxins and Plasmodium infection or gestational age. Results Eotaxin-2 concentrations in plasma showed a weak positive correlation with eotaxin-3 (rho = 0.35, p

Abstract Background European travellers to endemic countries are at risk of malaria and may be affected by a different range of co-morbidities than natives of endemic regions. The safety profile, especially cardiac issues, of artenimol (previously dihydroartemisinin)–piperaquine (APQ) Eurartesim® during treatment of uncomplicated imported falciparum malaria is not adequately described due to the lack of longitudinal studies in this population. The present study was conducted to partially fill this gap. Methods Participants were recruited through Health Care Provider’s safety registry in 15 centres across 6 European countries in the period 2013–2016. Adverse events (AE) were collected, with a special focus on cardiovascular safety by including electrocardiogram QT intervals evaluated after correction with either Bazett’s (QTcB) or Fridericia’s (QTcF) methods, at baseline and after treatment. QTcB and/or QTcF prolongation were defined by a value > 450 ms for males and children and > 470 ms for females. Results Among 294 participants, 30.3% were women, 13.7% of Caucasian origin, 13.5% were current smoker, 13.6% current alcohol consumer and 42.2% declared at least one illness history. The mean (SD) age and body mass index were 39.8 years old (13.2) and 25.9 kg/m2 (4.7). Among them, 75 reported a total of 129 AE (27 serious), 46 being suspected to be related to APQ (11 serious) and mostly labelled as due to haematological, gastrointestinal, or infection. Women and Non-African participants had significantly (p 500 ms (milliseconds) but no clinical symptoms. Using QTcB correction increases of > 60 ms were present in 9 participants (6.3%). A trend towards increased prolongation was observed in those over 65 years of age but only a few subjects were in this group. No new safety signal was reported. The overall efficacy rate was 255/257 (99.2%). Conclusions APQ appears as an effective and well-tolerated drug for treatment of malaria in patients recruited in European countries. AEs and QT prolongation were in the range of those obtained in larger cohorts from endemic countries. Trial registration This study has been registered in EU Post-Authorization Studies Register as EUPAS6942

Resumo em Português Antecedentes Moçambique tem uma das maiores taxas de incidência de cancro do colo do útero no mundo. As intervenções de saúde para o cancro do colo do útero ainda têm sido concebidas apenas do ponto de vista de doenças não transmissíveis, apesar do cancro do colo do útero ser também uma problema de saúde sexual e reprodutiva. O objectivo do estudo foi de avaliar em que medida as percepções leigas sobre o cancro do colo do útero alinham-se com o conhecimento biomédico do ponto de vista de saúde sexual e reprodutiva. Métodos Foram realizadas 10 discussões em grupos focais com 10 grupos-alvo no distrito de Manhiça. Os grupos-alvo eram diversos em termos de idade, sexo, nível de educação e ocupação. O estudo envolveu um total 116 participantes. As discussões em grupos focais geraram informação verbal e desencadearam debates sobre crenças e atitudes em relação ao cancro do colo do útero, e também exploraram noções de transmissão e etiologia da doença. As discussões foram gravadas para posterior transcrição e análise, seguindo uma combinação de análise de conteúdo e temática. Resultados Os participantes estavam familiarizados com o termo biomédico “cancro do colo do útero “, mas o seu conhecimento sobre a sua etiologia e transmissão era limitado. O cancro do colo do útero foi associado à transmissão sexual e infecções sexualmente transmissíveis e concebido como uma “ferida que não cicatriza”. O termo “cancro” causou confusão, pois era percebido como ocorrendo apenas nos membros do corpo, entendido como hereditário, não transmissível e como uma doença do Ocidente. Conclusão As percepções leigas sobre o cancro do colo do útero alinham-se, em grande parte às definições biomédicas, portanto, há uma estrutura de base comum para enquadrar futuras intervenções de saúde do ponto de vista da saúde sexual e reprodutiva.

Abstract Objectives The primary objectives of the study are: 1. To assess the effect of hydroxychloroquine (HCQ) in reducing SARS-CoV-2 viral shedding by PCR in infected pregnant women with mild symptoms. 2. To assess the efficacy of HCQ to prevent SARS-CoV-2 infection in pregnant women in contact with an infected or suspected case. 3. To evaluate the effect of HCQ in preventing the development of the COVID-19 disease in asymptomatic SARS-CoV-2-infected pregnant women. The secondary objectives are: 1. To determine the effect of HCQ on the clinical course and duration of the COVID-19 disease in SARS-CoV-2-infected pregnant women. 2. To determine the impact of HCQ on the risk of hospitalization and mortality of SARS-CoV-2-infected pregnant women. 3. To assess the safety and tolerability of HCQ in pregnant women. 4. To describe the clinical presentation of SARS-CoV-2 infection during pregnancy. 5. To describe the effects of maternal SARS-CoV-2 infection on pregnancy and perinatal outcomes by treatment group. 6. To determine the risk of vertical transmission (intra-utero and intra-partum) of SARS-CoV-2. Trial design Randomized double-blind placebo-controlled two-arm multicentre clinical trial to evaluate the safety and efficacy of HCQ to prevent and/or minimize SARS-CoV-2 infection during pregnancy. Participants will be randomized to receive a 14-day oral treatment course of HCQ or placebo, ratio 1:1. Participants Study population: pregnant women undergoing routine prenatal follow up or attending emergency units at the participating hospitals who report either symptoms/signs suggestive of COVID-19 disease or close contact with a suspected or confirmed COVID-19 case. Inclusion criteria Women will be invited to participate in the trial and sign an informed consent if they meet the following inclusion criteria. • Presenting with fever (≥37.5°C) and/or one mild symptom suggestive of COVID-19 disease (cough, dyspnoea, chills, odynophagia, diarrhoea, muscle pain, anosmia, dysgeusia, headache) OR being contact* of a SARS-CoV-2 confirmed or suspected case in the past 14 days • More than 12 weeks of gestation (dated by ultrasonography) • Agreement to deliver in the study hospitals Exclusion criteria • Known hypersensitivity to HCQ or other 4-amonoquinoline compounds • History of retinopathy of any aetiology • Concomitant use of digoxin, cyclosporine, cimetidine • Known liver disease • Clinical history of cardiac pathology including known long QT syndrome • Unable to cooperate with the requirements of the study • Participating in other intervention studies • Delivery onset (characterized by painful uterine contractions and variable changes of the cervix, including some degree of effacement and slower progression of dilatation up to 5 cm for first and subsequent labours) The study participants will be stratified by clinical presentation and SARS-CoV-2 PCR results. Assignment of participants to study groups will be as follows: • SARS-CoV-2-PCR confirmed, infected pregnant women: a. symptomatic (n=100) b. asymptomatic (n=100) • SARS-CoV-2 PCR negative pregnant women in contact* with a SARS-CoV-2-infected confirmed or suspected case (n=514). *The ECDC definition of close contact will be followed. The trial will be conducted in five hospitals in Spain: Hospital Clínic of Barcelona, Hospital Sant Joan de Déu and Hospital de la Santa Creu i Sant Pau, in Barcelona, and HM Puerta del Sur and Hospital Universitario de Torrejón, in Madrid. Intervention and comparator Participants will be randomized to HCQ (400 mg/day for three days, followed by 200 mg/day for 11 days) or placebo (2 tablets for three days, followed by one tablet for 11 days). Main outcomes The primary outcome is the number of PCR-confirmed infected pregnant women assessed from collected nasopharyngeal and oropharyngeal swabs at day 21 after treatment start (one week after treatment is completed). Randomisation Allocation of participants to study arms will be done centrally by the trial’s Sponsor (the Barcelona Institute for Global Health, ISGlobal) by block randomization. This method will ensure balanced allocation to both arms. The electronic CRF will automatically assign a study number to each participant, depending on her study group and recruitment site. Each number will be related to a treatment number, which assigns them to one of the study arms. Blinding (masking) Participants, caregivers, investigators and those assessing the outcomes will be blinded to group assignment. Study tablets (HCQ and placebo) will be identically packaged in small opaque bottles. Numbers to be randomised (sample size) This study requires 200 SARS-CoV-2 infected and 514 contact pregnant women, randomised 1:1 with 100 and 227 respectively in each study arm. Trial Status Protocol version 1.0, from May 8th, 2020. Recruitment is ongoing (first patient recruited the 19th May 2020 and recruitment end anticipated by December 2020). Trial registration EudraCT number: 2020-001587-29, registered 2 April 2020. Clinicaltrials.gov identifier: NCT04410562 , retrospectively registered 1 June 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Abstract Background Disruption of malaria control strategies during the West African 2014–2016 Ebola epidemic led to an increase in malaria-attributable mortality. However, recent data on malaria infection in vulnerable groups, such as pregnant women, are lacking in this post-Ebola scenario. This cross-sectional study aimed to assess the prevalence of Plasmodium falciparum infection and of molecular markers of drug resistance among pregnant women attending antenatal care in Monrovia, capital of Liberia. Methods From October 2016 to June 2017, all pregnant women attending their first antenatal care visit at the Saint Joseph’s Catholic Hospital, Monrovia, were invited to participate in the study. In addition to their routine antenatal care tests, capillary blood spotted onto filter papers were collected from all consenting participants to determine presence of P. falciparum by real-time quantitative PCR. Molecular markers of anti-malarial drug resistance were assessed through Sanger sequencing and quantitative PCR in specimens positive for P. falciparum analysis. Results Of the 195 women participants, 24 (12.3%) were P. falciparum-positive by qPCR. Infected women tended to be more commonly primigravidae and younger than uninfected ones. Parasite densities were higher in primigravidae. Fever was more frequently detected among the infected women. No statistically significant association between P. falciparum infection and haemoglobin levels or insecticide-treated net use was found. While high prevalence of genetic polymorphisms associated with chloroquine and amodiaquine resistance were detected, no molecular markers of artemisinin resistance were observed. Conclusion Plasmodium falciparum infections are expected to occur in at least one in every eight women attending first ANC at private clinics in Monrovia and outside the peak of the rainy season. Young primigravidae are at increased risk of P. falciparum infection. Molecular analyses did not provide evidence of resistance to artemisinins among the P. falciparum isolates tested. Further epidemiological studies involving pregnant women are necessary to describe the risk of malaria in this highly susceptible group outside Monrovia, as well as to closely monitor the emergence of resistance to anti-malarials, as recommended by the Liberian National Malaria Control Programme.

Abstract Background Social accountability mechanisms have been highlighted as making a contribution to improving maternal health outcomes and reducing inequities. But there is a lack of evidence on how they contribute to such improvements. This study aims to explore social accountability mechanisms in selected districts of the Indian state of Gujarat in relation to maternal health, the factors they address and how the results of these mechanisms are perceived. Methods We conducted qualitative research through in-depth interviews and focus group discussions with actors of civil society and government health system. Data were analyzed using a framework of social determinants of maternal health in terms of structural and intermediary determinants. Results There are social accountability mechanisms in the government and civil society in terms of structure and activities. But those that were perceived to influence maternal health were mainly from civil society, particularly women’s groups, community monitoring and a maternal death review. The social accountability mechanisms influenced structural determinants – governance, policy, health beliefs, women’s status, and intermediary determinants – social capital, maternal healthcare behavior, and availability, accessibility and the quality of the health service delivery system. These further positively influenced the increased use of maternal health services. The social accountability mechanisms, through the process of information, dialogue and negotiation, particularly empowered women to make collective demands of the health system and brought about changed perceptions of women among actors in the system. It ultimately improved relations between women and the health system in terms of trust and collaboration, and generated appropriate responses from the health system to meeting women’s groups’ demands. Conclusion Social accountability mechanisms in Gujarat were perceived to improve interaction between communities and the health system and contribute to improvements in access to and use of maternal health services. The influence of social accountability appeared to be limited to the local/district level and there was lack of capacity and ownership of the government structures.

Abstract Background Quality antenatal care (ANC) is recognised as an opportunity for screening and early identification of pregnancy-related complications. In rural Ghana, challenges with access to diagnostic services demotivate women from ANC attendance and referral compliance, leading to absent or late identification and management of high-risk women. In 2016, an integrated diagnostic and clinical decision support system tagged ‘Bliss4Midwives’ (B4M), was piloted in Northern Ghana. The device facilitated non-invasive screening of pre-eclampsia, gestational diabetes and anaemia at the point-of-care. This study aimed to explore the experiences of pregnant women with B4M, and its influence on service utilisation (“pull effect”) and woman-provider relationships (“woman engagement”). Methods Through an embedded study design, qualitative methods including individual semi-structured interviews and non-participant observation were employed. Interviews were conducted with 20 pregnant women and 10 health workers, supplemented by ANC observations in intervention facilities. Secondary data on ANC registrations over a one-year period were extracted from health facility records to support findings on the perceived influence of B4M on service utilisation. Results Women’s first impressions of the device were mostly emotive (excitement, fear), but sometimes neutral. Although it is inconclusive whether B4M increased ANC registration, pregnant women generally valued the availability of diagnostic services at the point-of-care. Additionally, by fostering some level of engagement, the intervention made women feel listened to and cared for. Process outcomes of the B4M encounter also showed that it was perceived as improving the skills and knowledge of the health worker, which facilitated trust in diagnostic recommendations and was therefore believed to motivate referral compliance. Conclusions This study suggests that mHealth diagnostic and decision support devices enhance woman engagement and trust in health workers skills. There is need for further inquiry into how these interventions influence maternal health service utilization and women’s expectations of pregnancy care.

Abstract The goal to eliminate malaria from the Asia-Pacific by 2030 will require the safe and widespread delivery of effective radical cure of malaria. In October 2017, the Asia Pacific Malaria Elimination Network Vivax Working Group met to discuss the impediments to primaquine (PQ) radical cure, how these can be overcome and the methodological difficulties in assessing clinical effectiveness of radical cure. The salient discussions of this meeting which involved 110 representatives from 18 partner countries and 21 institutional partner organizations are reported. Context specific strategies to improve adherence are needed to increase understanding and awareness of PQ within affected communities; these must include education and health promotion programs. Lessons learned from other disease programs highlight that a package of approaches has the greatest potential to change patient and prescriber habits, however optimizing the components of this approach and quantifying their effectiveness is challenging. In a trial setting, the reactivity of participants results in patients altering their behaviour and creates inherent bias. Although bias can be reduced by integrating data collection into the routine health care and surveillance systems, this comes at a cost of decreasing the detection of clinical outcomes. Measuring adherence and the factors that relate to it, also requires an in-depth understanding of the context and the underlying sociocultural logic that supports it. Reaching the elimination goal will require innovative approaches to improve radical cure for vivax malaria, as well as the methods to evaluate its effectiveness.