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There is a recognised need for innovative methods to elicit the perspective of adolescents on public health issues, particularly when addressing sensitive topics such as the impact of mining projects on their health. Participatory approaches such as “photovoice” allow for deep engagement of vulnerable and marginalised populations, including adolescents. However, few existing studies have used the photovoice method to reflect on issues related to the environment and its impact on public health. To date, no studies have been found that have used photovoice to gain insight into adolescentsʼ perspectives in mining areas. In this paper, we discuss the application of the photovoice method to understand adolescents’ perceptions about the impact of mining on their health and well-being in rural areas in Mozambique. The study was conducted in northern and central Mozambique. Photovoice was successfully integrated into eight focus group discussions with adolescent girls and boys aged 15 to 17 years. Several lessons for guiding future research were learned. First, it provided an understanding of the perceived impacts of mining on their health and well-being. Second, photovoice promoted active engagement and interest in the study by the adolescents. Finally, compared to its ability to capture perceptions of physical and environmental aspects affecting adolescents’ well-being, the method was less straightforward in revealing their concerns regarding social, relational and community aspects that are less tangible. Programs can make use of photovoice to address health issues without setting adolescents’ views and priorities aside, allowing them to influence health decisions on issues that are meaningful to them. Future studies should explore strategies to minimise the role of the power dynamics that affect the engagement and contribution of adolescents in advocating for necessary and meaningful changes. Additionally, it is important to investigate how health programs and policies can help to reduce the impact of existing inequalities.

Abstract Routine sampling of pregnant women at first antenatal care (ANC) visits could make Plasmodium falciparum genomic surveillance more cost-efficient and convenient in sub-Saharan Africa. We compare the genetic structure of parasite populations sampled from 289 first ANC users and 93 children from the community in Mozambique between 2015 and 2019. Samples are amplicon sequenced targeting 165 microhaplotypes and 15 drug resistance genes. Metrics of genetic diversity and relatedness, as well as the prevalence of drug resistance markers, are consistent between the two populations. In an area targeted for elimination, intra-host genetic diversity declines in both populations (p = 0.002-0.007), while for the ANC population, population genetic diversity is also lower (p = 0.0004), and genetic relatedness between infections is higher (p = 0.002) than control areas, indicating a recent reduction in the parasite population size. These results highlight the added value of genomic surveillance at ANC clinics to inform about changes in transmission beyond epidemiological data.

Introduction The burden of severe maternal morbidity is highest in sub-Saharan Africa, and its relative contribution to maternal (ill) health may increase as maternal mortality continues to fall. Women’s perspective of their long-term recovery following severe morbidity beyond the standard 42-day postpartum period remains largely unexplored.Methods This woman-centred, grounded theory study was nested within the Pregnancy Care Integrating Translational Science Everywhere (PRECISE) study in Kilifi, Kenya. Purposive and theoretical sampling was used to recruit 20 women who experienced either a maternal near-miss event (n=11), potentially life-threatening condition (n=6) or no severe morbidity (n=3). Women were purposively selected between 6 and 36 months post partum at the time of interview to compare recovery trajectories. Using a constant comparative approach of line-by-line open codes, focused codes, super-categories and themes, we developed testable hypotheses of women’s postpartum recovery trajectories after severe maternal morbidity.Results Grounded in women’s accounts of their lived experience, we identify three phases of recovery following severe maternal morbidity: ‘loss’, ‘transition’ and ‘adaptation to a new normal’. These themes are supported by multiple, overlapping super-categories: loss of understanding of own health, functioning and autonomy; transition in women’s identity and relationships; and adaptation to a new physical, psychosocial and economic state. This recovery process is multidimensional, potentially cyclical and extends far beyond the standard 42-day postpartum period.Conclusion Women’s complex needs following severe maternal morbidity require a reconceptualisation of postpartum recovery as extending far beyond the standard 42-day postpartum period. Women’s accounts expose major deficiencies in the provision of postpartum and mental healthcare. Improved postpartum care provision at the primary healthcare level, with reach extended through community health workers, is essential to identify and treat chronic mental or physical health problems following severe maternal morbidity.

Abstract Pregnant women attending first antenatal care (ANC) visits represent a promising malaria surveillance target in Sub-Saharan Africa. We assessed the spatio-temporal relationship between malaria trends at ANC (n = 6471) and in children in the community (n = 3933) and at health facilities (n = 15,467) in southern Mozambique (2016–2019). ANC P. falciparum rates detected by quantitative polymerase chain reaction mirrored rates in children, regardless of gravidity and HIV status (Pearson correlation coefficient [PCC] > 0.8, χ²

Abstract Background Low-density Plasmodium falciparum infections prevail in low transmission settings, where immunity is expected to be minimal, suggesting an immune-independent effect on parasite densities. We aimed to describe parasite densities in pregnancy, and determine how gravidity and antibody-mediated immunity affect these, during a period of declining malaria transmission in southern Mozambique. Methods We documented P. falciparum infections at first antenatal care visits (n = 6471) between November 2016 and October 2019 in Ilha Josina (high-to-moderate transmission area), Manhiça (low transmission area), and Magude (pre-elimination area). Two-way interactions in mixed-effects regression models were used to assess gravidity-dependent differences in quantitative PCR-determined P. falciparum positivity rates (PfPRqPCR) and densities, in the relative proportion of detectable infections (pDi) with current diagnostic tests (≥ 100 parasites/μL) and in antimalarial antibodies. Results PfPRqPCR declined from 28 to 13% in Ilha Josina and from 5–7 to 2% in Magude and Manhiça. In primigravidae, pDi was highest in Ilha Josina at the first study year (p = 0.048), which declined with falling PfPRqPCR (relative change/year: 0.41, 95% CI [0.08; 0.73], p = 0.029), with no differences in antibody levels. Higher parasite densities in primigravidae from Ilha Josina during the first year were accompanied by a larger reduction of maternal hemoglobin levels (− 1.60, 95% CI [− 2.49; − 0.72; p

Abstract Background The African continent hosts many industrial mining projects, and many more are planned due to recent prospecting discoveries and increasing demand for various minerals to promote a low-carbon future. The extraction of natural resources in sub-Saharan Africa (SSA) represents an opportunity for economic development but also poses a threat to population health through rapid urbanisation and environmental degradation. Children could benefit from improved economic growth through various channels such as access to high-quality food, better sanitation, and clean water. However, mining can increase food insecurity and trigger local competition over safe drinking water. Child health can be threatened by exposure to mining-related air, noise, and water pollution. To assess the impact of mines on child health, we analyse socio-demographic, health, and mining data before and after several mining projects were commissioned in SSA. Results Data of 90,951 children living around 81 mining sites in 23 countries in SSA were analysed for child mortality indicators, and 79,962 children from 59 mining areas in 18 SSA countries were analysed for diarrhoea, cough, and anthropometric indicators. No effects of the launch of new mining projects on overall under-five mortality were found (adjusted Odds Ratio (aOR): 0.88; 95% Confidence Interval (CI): 0.68–1.14). However, activation of mining projects reduced the mortality risk among neonates (0–30 days) by 45% (aOR: 0.55; 95% CI: 0.37–0.83) and risk for a child to develop diarrhoeal diseases by 32% (aOR: 0.68; 95% CI: 0,51–0.90). The timing analysis of observed changes showed that there is a significant decline in the risk for childhood diarrhoea (aOR: 0.69; 95% CI: 0.49–0.97), and the mean height-for-age z-scores by 28 percentage points, during the prospection and construction phase; i.e., within four years to the initiation of extraction activity. No effects were found for cough and weight-for-height. Conclusion The results presented suggest that the impacts of mining on child health vary throughout the mine’s life cycle. Mining development likely contributes positively to the income and livelihoods of the impacted communities in the initial years of mining operations, particularly the prospection and construction phase; these potential benefits are likely to be at least partially offset by food insecurity and environmental pollution during early and later mining stages, respectively. Further research is warranted to better understand these health impacts and to identify policies that can help sustain the positive initial health impacts of mining projects in the long term.

Abstract Background Due to the threat of emerging anti-malarial resistance, the World Health Organization recommends incorporating surveillance for molecular markers of anti-malarial resistance into routine therapeutic efficacy studies (TESs). In 2018, a TES of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) was conducted in Mozambique, and the prevalence of polymorphisms in the pfk13, pfcrt, and pfmdr1 genes associated with drug resistance was investigated. Methods Children aged 6–59 months were enrolled in four study sites. Blood was collected and dried on filter paper from participants who developed fever within 28 days of initial malaria treatment. All samples were first screened for Plasmodium falciparum using a multiplex real-time PCR assay, and polymorphisms in the pfk13, pfcrt, and pfmdr1 genes were investigated by Sanger sequencing. Results No pfk13 mutations, associated with artemisinin partial resistance, were observed. The only pfcrt haplotype observed was the wild type CVMNK (codons 72–76), associated with chloroquine sensitivity. Polymorphisms in pfmdr1 were only observed at codon 184, with the mutant 184F in 43/109 (39.4%) of the samples, wild type Y184 in 42/109 (38.5%), and mixed 184F/Y in 24/109 (22.0%). All samples possessed N86 and D1246 at these two codons. Conclusion In 2018, no markers of artemisinin resistance were documented. Molecular surveillance should continue to monitor the prevalence of these markers to inform decisions on malaria treatment in Mozambique.

Abstract Background Artemisinin-based combination therapy (ACT) has been the recommended first-line treatment for uncomplicated malaria in Mozambique since 2006, with artemether–lumefantrine (AL) and amodiaquine–artesunate (AS–AQ) as the first choice. To assess efficacy of currently used ACT, an in vivo therapeutic efficacy study was conducted. Methods The study was conducted in four sentinel sites: Montepuez, Moatize, Mopeia and Massinga. Patients between 6 and 59 months old with uncomplicated Plasmodium falciparum malaria (2000–200,000 parasites/µl) were enrolled between February and September of 2018, assigned to either an AL or AS–AQ treatment arm, and monitored for 28 days. A Bayesian algorithm was applied to differentiate recrudescence from new infection using genotyping data of seven neutral microsatellites. Uncorrected and PCR-corrected efficacy results at day 28 were calculated. Results Totals of 368 and 273 patients were enrolled in the AL and AS–AQ arms, respectively. Of these, 9.5% (35/368) and 5.1% (14/273) were lost to follow-up in the AL and AS–AQ arms, respectively. There were 48 and 3 recurrent malaria infections (late clinical and late parasitological failures) in the AL and AS–AQ arms, respectively. The day 28 uncorrected efficacy was 85.6% (95% confidence interval (CI) 81.3–89.2%) for AL and 98.8% (95% CI 96.7–99.8%) for AS–AQ, whereas day 28 PCR-corrected efficacy was 97.9% (95% CI 95.6–99.2%) for AL and 99.6% (95% CI 97.9–100%) for AS–AQ. Molecular testing confirmed that 87.4% (42/48) and 33.3% (1/3) of participants with a recurrent malaria infection in the AL and AS–AQ arms were new infections; an expected finding in a high malaria transmission area. Adverse events were documented in less than 2% of participants for both drugs. Conclusion Both AL and AS–AQ have therapeutic efficacies well above the 90% WHO recommended threshold and remain well-tolerated in Mozambique. Routine monitoring of therapeutic efficacy should continue to ensure the treatments remain efficacious. Trial registration Clinicaltrials.gov: NCT04370977

Plain Language Summary Maternal mortality is an important public health problem in Mozambique. Delays in reaching health facilities and insufficient health care professionals call for innovative community-level solutions. We conducted a study to describe the feasibility of task-sharing the screening and initiation of management for pre-eclampsia/eclampsia from the primary healthcare providers to community health workers in Mozambique and to document healthcare facility preparedness to respond to referrals. The study was done to inform a future intervention trial known as the Community-Level Interventions for Pre-eclampsia (CLIP) study. We interviewed community health workers, women, various community groups, health care providers, and policymakers and assessed health facilities in Maputo and Gaza provinces, Mozambique. Our results showed that community health workers in Mozambique were trained to identify the basic danger signs of pregnancy; however, they were not trained or equipped to provide obstetric emergencies care prior to referral. Nurses at primary health facilities were supportive of task-sharing with community health workers; however, some barriers mentioned include a lack of equipment, shortage of supervisors, and irregular drug availability. Local stakeholders emphasized the need for comprehensive training and supervision of community health workers to take on new tasks. Task-sharing for screening and pre-referral management of pre-eclampsia and eclampsia was deemed feasible at the community level in southern Mozambique, but still, to be addressed some health system level barriers to the management of pregnancies complications.

Abstract Background While there is increasing evidence on the safety of artemisinin-based combination therapy (ACT) for the case management of malaria in early pregnancy, little is known about the association between exposure to ACT during the first trimester and the effect on fetal growth. Methods Data were analysed from prospective studies of pregnant women enrolled in Mozambique, Burkina Faso and Kenya designed to determine the association between anti-malarial drug exposure in the first trimester and pregnancy outcomes, including low birth weight (LBW) and small for gestational age (SGA). Exposure to anti-malarial drugs was ascertained retrospectively by record linkage using a combination of data collected from antenatal and adult outpatient clinic registries, prescription records and self-reported medication usage by the women. Site-level data synthesis (fixed effects and random effects) was conducted as well as individual-level analysis (fixed effects by site). Results Overall, 1915 newborns were included with 92 and 26 exposed to ACT (artemether–lumefantrine) and quinine, respectively. In Burkina Faso, Mozambique and Kenya at recruitment, the mean age (standard deviation) was 27.1 (6.6), 24.2 (6.2) and 25.7 (6.5) years, and the mean gestational age was 24.0 (6.2), 21.2 (5.7) and 17.9 (10.2) weeks, respectively. The LBW prevalence among newborns born to women exposed to ACT and quinine (QNN) during the first trimester was 10/92 (10.9%) and 7/26 (26.9%), respectively, compared to 9.5% (171/1797) among women unexposed to any anti-malarials during pregnancy. Compared to those unexposed to anti-malarials, ACT and QNN exposed women had the pooled LBW prevalence ratio (PR) of 1.13 (95% confidence interval (CI) 0.62–2.05, p-value 0.700) and 2.03 (95% CI 1.09–3.78, p-value 0.027), respectively. Compared to those unexposed to anti-malarials ACT and QNN-exposed women had the pooled SGA PR of 0.85 (95% CI 0.50–1.44, p-value 0.543) and 1.41 (95% CI 0.71–2.77, p-value 0.322), respectively. Whereas compared to ACT-exposed, the QNN-exposed had a PR of 2.14 (95% CI 0.78–5.89, p-value 0.142) for LBW and 8.60 (95% CI 1.29–57.6, p-value 0.027) for SGA. The level of between sites heterogeneity was moderate to high. Conclusion ACT exposure during the first trimester was not associated with an increased occurrence of LBW or SGA. However, the data suggest a higher prevalence of LBW and SGA for children born to QNN-exposed pregnancies. The findings support the use of ACT (artemether–lumefantrine) for the treatment of uncomplicated malaria during the first trimester of pregnancy.

Abstract Background Poor knowledge on the afebrile Plasmodium falciparum biology limits elimination approaches to target asymptomatic malaria. Therefore, the association of parasite factors involved in cytoadhesion, parasite multiplication and gametocyte maturation with afebrile malaria was assessed. Methods Plasmodium falciparum isolates were collected from febrile (axillary temperature ≥ 37.5 °C or a reported fever in the previous 24 h) and afebrile (fever neither at the visit nor in the previous 24 h) individuals residing in Southern Mozambique. var, PfSir2a and Pfs25 transcript levels were determined by reverse transcriptase quantitative PCRs (RT-qPCRs) and compared among 61 pairs of isolates matched by parasite density, age and year of sample collection. Results The level of varC and PfSir2a transcripts was higher in P. falciparum isolates from afebrile individuals (P ≤ 0.006), while varB and DC8 genes (P ≤ 0.002) were higher in isolates from individuals with febrile infections. After adjusting the analysis by area of residence, doubling the relative transcript unit (RTU) of varC and PfSir2a was associated with a 29.7 (95% CI 4.6–192.3) and 8.5 (95% CI 1.9–32.2) fold increases, respectively, of the odds of being afebrile. In contrast, doubling the RTU of varB and DC8 was associated with a 0.8 (95% CI 0.05–0.6) and 0.2 (95% CI 0.04–0.6) fold changes, respectively, of the odds of being afebrile. No significant differences were found for Pfs25 transcript levels in P. falciparum isolates from afebrile and febrile individuals. Conclusions var and gametocyte-specific transcript patterns in febrile and afebrile infections from southern Mozambique matched by age, parasite density and recruitment period suggest similar transmissibility but differential expression of variant antigens involved in cytoadhesion and immune-evasion.

Abstract Background In Mozambique cervical cancer is a public health threat, due to its high incidence and limited access to early diagnosis of precancerous lesions. International organisations are supporting the introduction of human papillomavirus (HPV) vaccines in low- and middle-income countries. Some of these countries recently conducted demonstration programmes, which included evaluation of acceptability, coverage, and practicality of implementation and of integration in existing programmes. Information on costs of delivering the vaccine is needed to overcome the challenges of reaching vaccine potential recipients in rural and remote areas. Methods We estimated the financial and economic costs of delivering HPV vaccination to ten-year-old girls at schools for the first vaccination cycle of the demonstration programme in the Manhiça district (southern Mozambique), delivered throughout 2014. We also estimated costs of an alternative scenario with a reduced number of doses and personnel, which was analogous to the second vaccination cycle delivered throughout 2015. Cost estimates followed a micro-costing approach and included interviews with key informants at different administrative levels through the administration of standard questionnaires developed by the World Health Organisation. Results Considering only data from the first vaccination cycle (2014), which consisted in the administration of three doses, the average economic cost was US$17.59 per dose and US$52.29 per fully-immunised girl (FIG). Financial cost per dose (US$6.07) and per FIG (US$17.95) were substantially lower. The economic cost was US$15.53 per dose and US$31.14 per FIG when estimating an alternative cost scenario with reduced number of doses and personnel. Conclusions The average economic cost per dose was lower than the ones recently reported for low- and middle-income countries. However, our estimation of the financial cost per FIG was higher than the ones observed elsewhere (ranging from US$2.49 in India to US$20.36 in Vietnam) due to the high percentage of out-of-school girls which, reduced vaccine coverage and, therefore, reduced the denominator. Due to budget constraints, if Mozambique is to implement nation-wide HPV vaccination targeted to ten-year-old girls at schools, a reduction in personnel costs should be operated either by restricting the outreach vaccinator team or the number of supervision visits.

Abstract Mozambique has historically been one of the countries with the highest malaria burden in the world. Starting in the 1960s, malaria control efforts were intensified in the southern region of the country, especially in Maputo city and Maputo province, to aid regional initiatives aimed to eliminate malaria in South Africa and eSwatini. Despite significant reductions in malaria prevalence, elimination was never achieved. Following the World Health Organization’s renewed vision of a malaria-free-world, and considering the achievements from the past, the Mozambican National Malaria Control Programme (NMCP) embarked on the development and implementation of a strategic plan to accelerate from malaria control to malaria elimination in southern Mozambique. An initial partnership, supported by the Bill and Melinda Gates Foundation and the La Caixa Foundation, led to the creation of the Mozambican Alliance Towards the Elimination of Malaria (MALTEM) and the Malaria Technical and Advisory Committee (MTAC) to promote national ownership and partner coordination to work towards the goal of malaria elimination in local and cross-border initiatives. Surveillance systems to generate epidemiological and entomological intelligence to inform the malaria control strategies were strengthened, and an impact and feasibility assessment of various interventions aimed to interrupt malaria transmission were conducted in Magude district (Maputo Province) through the “Magude Project”. The primary aim of this project was to generate evidence to inform malaria elimination strategies for southern Mozambique. The goal of malaria elimination in areas of low transmission intensity is now included in the national malaria strategic plan for 2017–22 and the NMCP and its partners have started to work towards this goal while evidence continues to be generated to move the national elimination agenda forward.

Abstract Background Despite major improvements in child survival rates, the number of deaths due to diarrhea remains unacceptably high. We aimed to describe diarrhea-associated mortality and evaluate risk factors for death among Mozambican children with moderate-to-severe diarrhea (MSD). Methods Between December 2007 and November 2012, children under-five with MSD were enrolled in Manhiça district, as part of the Global Enteric Multicenter study (GEMS). Clinical, epidemiological, and socio-demographic characteristics were collected. Anthropometric measurements were performed and stool samples collected upon recruitment. A follow-up visit ~ 60 days post-enrolment was conducted and verbal autopsies performed in all death cases. Results Of the 916 MSD-cases analyzed; 90% (821/916) completed 60 days follow-up and 69 patients died. The case fatality rate at follow-up was 8% (69/821), and the mortality rate 10.2 (95%CI: 7.75–13.59) deaths per 1000 persons-week at risk. Nearly half of the deaths 48% (33/69) among study participants clustered within 2 weeks of the onset of diarrhea. Typical enteropathogenic Escherichia coli (typical EPEC) and Cryptosporidium were the two pathogens associated to an increased risk of death in the univariate analysis with (HR = 4.16, p = 0.0461) and (H = 2.84, p = 0.0001) respectively. Conversely, Rotavirus infection was associated to a decreased risk of death (HR = 0.52, p = 0.0198). According to the multivariate analysis, risk factors for death included co-morbidities such as malnutrition (HR = 4.13, p

Background Global malaria mortality estimates are hindered by the low reliability of the verbal autopsy (VA) and the clinical records, the most common sources of information used to estimate malaria-specific mortality. We aimed to determine the accuracy of these tools, as well as of the minimally invasive autopsy (MIA), a needle-based postmortem sampling method, to identify malaria-specific mortality in a large series of deceased patients from Mozambique, using complete autopsy as the gold standard.Methods Observational study that included 264 deaths, occurring at a tertiary level hospital in Mozambique, from 1 November 2013 to 31 March 2015 (17 months-long period). Clinical data were abstracted, a computer coded VA was completed using the clinical data as source of information, and an MIA followed by a complete autopsy were performed. Screening for malaria infection was conducted postmortem to all participants using molecular and histological techniques (PCR and immunohistochemistry).Findings Malaria infection was considered the cause of death in 6/264 (2.3%) cases: 2/54 children (3.7%, both less than 5 years old) and 4/57 (7.0%) maternal deaths. The sensitivity and specificity of the VA, the clinical data and the MIA to identify malaria-specific deaths were 33.3% and 96.1%, 66.7% and 96.1%, and 100% and 100%, respectively. In addition, malaria was identified as a possible contributor in 14 additional patients who died of other diseases. These cases were also accurately identified by the MIA (sensitivity 82.4%, specificity 100%).Interpretation The high sensitivity and specificity of the MIA in identifying malaria may help to improve current estimates of malaria-specific mortality in endemic areas.

An amendment to this paper has been published and can be accessed via the original article.

Background Technological advances and high throughput biological assays can facilitate discovery science in biobanks from population cohorts, including pregnant women. Biological pathways associated with health outcomes differ depending on geography, and high-income country data may not generalise to low-resource settings. We conducted a systematic review to identify prospective pregnancy cohorts in sub-Saharan Africa (SSA) that include biobanked samples with potential to enhance discovery science opportunity.Methods Inclusion criteria were prospective data collection during pregnancy, with associated biobanking in SSA. Data sources included: scientific databases (with comprehensive search terms), grey literature, hand searching applicable reference lists and expert input. Results were screened in a three-stage process based on title, abstract and full text by two independent reviewers. The review is registered on PROSPERO (CRD42019147483).Results Fourteen SSA studies met the inclusion criteria from database searches (n=8), reference list searches (n=2) and expert input (n=4). Three studies have ongoing data collection. The most represented countries were South Africa and Mozambique (Southern Africa) (n=3), Benin (Western Africa) (n=4) and Tanzania (Eastern Africa) (n=4); including an estimated 31 763 women. Samples commonly collected were blood, cord blood and placenta. Seven studies collected neonatal samples. Common clinical outcomes included maternal and perinatal mortality, malaria and preterm birth.Conclusions Increasingly numerous pregnancy cohorts in SSA that include biobanking are generating a uniquely valuable resource for collaborative discovery science, and improved understanding of the high regional risks of maternal, fetal and neonatal morbidity and mortality. Future studies should align protocols and consider their added value and distinct contributions.

Maternal factors and exposure to pathogens have an impact on infant health. For instance, HIV exposed but uninfected infants have higher morbidity and mortality than HIV unexposed infants. Innate responses are the first line of defense and orchestrate the subsequent adaptive immune response and are especially relevant in newborns. To determine the association of maternal HIV infection with maternal and newborn innate immunity we analyzed the cytokine responses upon pattern recognition receptor (PRR) stimulations in the triad of maternal peripheral and placental blood as well as in cord blood in a cohort of mother-infant pairs from southern Mozambique. A total of 48 women (35 HIV-uninfected and 13 HIV-infected) were included. Women and infant innate responses positively correlated with each other. Age, gravidity and sex of the fetus had some associations with spontaneous production of cytokines in the maternal peripheral blood. HIV-infected women not receiving antiretroviral therapy (ART) before pregnancy showed decreased IL-8 and IL-6 PRR responses in peripheral blood compared to those HIV-uninfected, and PRR hyporesponsiveness for IL-8 was also found in the corresponding infant’s cord blood. HIV infection had a greater impact on placental blood responses, with significantly increased pro-inflammatory, TH1 and TH17 PRR responses in HIV-infected women not receiving ART before pregnancy compared to HIV-uninfected women. In conclusion, innate response of the mother and her newborn was altered by HIV infection in the women who did not receive ART before pregnancy. As these responses could be related to birth outcomes, targeted innate immune modulation could improve maternal and newborn health.

Abstract Background Pre-eclampsia is one of the leading causes of maternal death in Mozambique. Limited access to health care facilities and a lack of skilled health professionals contribute to the high maternal morbidity and mortality rates in Mozambique and indicate a need for community-level interventions. The aim of this review was to identify and characterise health policies related to the role of CHWs in the management of pre-eclampsia and eclampsia in Mozambique. Methods The policy review was based on three methods: a desk review of relevant documents from the Mozambique Ministry of Health (n = 7), contact with 28 key informants in the field of health policy in Mozambique (n = 5) and literature review (n = 699). Policy documents obtained included peer-reviewed articles, government and institutional policies, reports and action plans. Seven hundred and eleven full-text documents were assessed for eligibility and included based on pre-defined criteria. Qualitative analysis was done to identify main themes using content analysis. Results A total of 56 papers informed the timeline of key events. Three main themes were identified from the qualitative review: establishment of the community health worker programme and early challenges, revitalization of the CHW programme and the integration of maternal health in the community health tasks. In 1978, following the Alma Alta Declaration, the Mozambique government brought in legislation establishing primary health care and the CHW programme. Between the late 1980s and early 1990s, this programme was scaled down due to several factors including a prolonged civil war; however, the decision to revitalise the programme was made in 1995. In 2010, a revitalised programme was re-launched and expanded to include the management of common childhood illnesses, detection of warning signs of pregnancy complications, referrals for maternal health and basic health promotion. To date, their role has not included management of emergency conditions of pregnancy including pre-eclampsia and eclampsia. Conclusion The role of CHWs has evolved over the last 40 years to include care of childhood diseases and basic maternal health counselling. Studies to assess the impact of CHWs in providing services to reduce maternal morbidity and mortality are recommended.

Objectives A Demographic and Health Platform was established in Magude in 2015, prior to the deployment of a project aiming to evaluate the feasibility of malaria elimination in southern Mozambique, named the Magude project. This platform aimed to inform the design, implementation and evaluation of the Magude project, through the identification of households and population; and the collection of demographic, health and malaria information.Setting Magude is a rural district of southern Mozambique which borders South Africa. It has nine peripheral health facilities and one referral health centre with an inpatient ward.Intervention A baseline census enumerated and geolocated all the households, and their resident and non-resident members, collecting demographic and socio-economic information, and data on the coverage and usage of malaria control tools. Inpatient and outpatient data during the 5 years (2010 to 2014) before the survey were obtained from the district health authorities. The demographic platform was updated in 2016.Results The baseline census conducted in 2015 reported 48 448 (92.1%) residents and 4133 (7.9%) non-residents, and 10 965 households. Magude’s population is predominantly young, half of the population has no formal education and the main economic activities are agriculture and fishing. Houses are mainly built with traditional non-durable materials and have poor sanitation facilities. Between 2010 and 2014, malaria was the most common cause of all-age inpatient discharges (representing 20% to 40% of all discharges), followed by HIV (12% to 22%) and anaemia (12% to 15%). In early 2015, all-age bed-net usage was between 21.8% and 27.1% and the reported coverage of indoor residual spraying varied across the district between 30.7% and 79%.Conclusion This study revealed that Magude has limited socio-economic conditions, poor access to healthcare services and low coverage of malaria vector control interventions. Thus, Magude represented an area where it is most pressing to demonstrate the feasibility of malaria elimination.Trial registration number NCT02914145; Pre-results.

Multidrug-resistant Escherichia coli ST131 fimH30 responsible for extra-intestinal pathogenic (ExPEC) infections is globally distributed. However, the occurrence of a subclone fimH27 of ST131 harboring both ExPEC and enteroaggregative E. coli (EAEC) related genes and belonging to commonly reported O25:H4 and other serotypes causing bacteremia in African children remain unknown. We characterized 325 E. coli isolates causing bacteremia in Mozambican children between 2001 and 2014 by conventional multiplex polymerase chain reaction and whole genome sequencing. Incidence rate of EAEC bacteremia was calculated among cases from the demographic surveillance study area. Approximately 17.5% (57/325) of isolates were EAEC, yielding an incidence rate of 45.3 episodes/105 children-years-at-risk among infants; and 44 of isolates were sequenced. 72.7% (32/44) of sequenced strains contained simultaneously genes associated with ExPEC (iutA, fyuA and traT); 88.6% (39/44) harbored the aggregative adherence fimbriae type V variant (AAF/V). Sequence type ST-131 accounted for 84.1% (37/44), predominantly belonging to serotype O25:H4 (59% of the 37); 95.6% (35/44) harbored fimH27. Approximately 15% (6/41) of the children died, and five of the six yielded ST131 strains (83.3%) mostly (60%; 3/5) due to serotypes other than O25:H4. We report the emergence of a new subclone of ST-131 E. coli strains belonging to O25:H4 and other serotypes harboring both ExPEC and EAEC virulence genes, including agg5A, associated with poor outcome in bacteremic Mozambican children, suggesting the need for prompt recognition for appropriate management.

Sub-Saharan Africa concentrates the largest burden of cervical cancer worldwide. The introduction of the HPV vaccination in this region is urgent and strategic to meet global health targets. This was a cross-sectional study conducted in Mozambique prior to the first round of the HPV vaccine demonstration programme. It targeted girls aged 10–19 years old identified from schools and households. Face-to-face structured interviews were conducted. A total of 1147 adolescents were enrolled in three selected districts of the country. Most girls [84% (967/1147)] had heard of cervical cancer, while 76% believed that cervical cancer could be prevented. However only 33% (373/1144) of girls recognized having ever heard of HPV. When girls were asked whether they would accept to be vaccinated if a vaccine was available in Mozambique, 91% (1025/1130) answered positively. Girls from the HPV demonstration districts showed higher awareness on HPV and cervical cancer, and willingness to be vaccinated. This study anticipates high acceptability of the HPV vaccine in Mozambique and high awareness about cervical cancer, despite low HPV knowledge. These results highlight that targeted health education programmes are critical for acceptance of new tools, and are encouraging for the reduction of cervical cancer related mortality and morbidity in Mozambique. Keywords: Human papillomavirus, Vaccine, Cervical cancer, Mozambique, Awareness and acceptability

Sub-Saharan Africa (SSA) has the highest proportion of people using unclean fuels for household energy, which can result in products of incomplete combustion that are damaging for health. Black carbon (BC) is a useful marker of inefficient combustion-related particles; however, ambient air quality data and temporal patterns of personal exposure to BC in SSA are scarce. We measured ambient elemental carbon (EC), comparable to BC, and personal exposure to BC in women of childbearing age from a semi-rural area of southern Mozambique. We measured ambient EC over one year (2014–2015) using a high-volume sampler and an off-line thermo-optical-transmission method. We simultaneously measured 5-min resolved 24-h personal BC using a portable MicroAeth (AE51) in 202 women. We used backwards stepwise linear regression to identify predictors of log-transformed 24-h mean and peak (90th percentile) personal BC exposure. We analyzed data from 187 non-smoking women aged 16–46 years. While daily mean ambient EC reached moderate levels (0.9 μg/m3, Standard Deviation, SD: 0.6 μg/m3), daily mean personal BC reached high levels (15 μg/m3, SD: 19 μg/m3). Daily patterns of personal exposure revealed a peak between 6 and 7 pm (>35 μg/m3), attributable to kerosene-based lighting. Key determinants of mean and peak personal exposure to BC were lighting source, kitchen type, ambient EC levels, and temperature. This study highlights the important contribution of lighting sources to personal exposure to combustion particles in populations that lack access to clean household energy. Keywords: Household air pollution, Personal monitoring, Black carbon, Kerosene, Sub-Saharan Africa

Reliable statistics on maternal morbidity and mortality are scarce in low and middle-income countries, especially in rural areas. This is the case in Mozambique where many births happen at home. Furthermore, a sizeable number of facility births have inadequate registration. Such information is crucial for developing effective national and global health policies for maternal and child health. The aim of this study was to generate reliable baseline socio-demographic information on women of reproductive age as well as to establish a demographic surveillance platform to support the planning and implementation of the Community Level Intervention for Pre-eclampsia (CLIP) study, a cluster randomized controlled trial. This study represents a census of all women of reproductive age (12-49 years) in twelve rural communities in Maputo and Gaza provinces of Mozambique. The data were collected through electronic forms implemented in Open Data Kit (ODK) (an app for android based tablets) and household and individual characteristics. Verbal autopsies were conducted on all reported maternal deaths to determine the underlying cause of death. Between March and October 2014, 50,493 households and 80,483 women of reproductive age (mean age 26.9 years) were surveyed. A total of 14,617 pregnancies were reported in the twelve months prior to the census, resulting in 9,029 completed pregnancies. Of completed pregnancies, 8,796 resulted in live births, 466 resulted in stillbirths and 288 resulted in miscarriages. The remaining pregnancies had not yet been completed during the time of the survey (5,588 pregnancies). The age specific fertility indicates that highest rate (188 live births per 1,000 women) occurs in the age 20-24 years old. The estimated stillbirth rate was 50.3/1,000 live and stillbirths; neonatal mortality rate was 13.3/1,000 live births and maternal mortality ratio was 204.6/100,000 live births. The most common direct cause of maternal death was eclampsia and tuberculosis was the most common indirect cause of death. This study found that fertility rate is high at age 20-24 years old. Pregnancy in the advanced age (>35 years of age) in this study was associated with higher poor outcomes such as miscarriage and stillbirth. The study also found high stillbirth rate indicating a need for increased attention to maternal health in southern Mozambique. Tuberculosis and HIV/AIDS are prominent indirect causes of maternal death, while eclampsia represents the number one direct obstetric cause of maternal deaths in these communities. Additional efforts to promote safe motherhood and improve child survival are crucial in these communities.

BACKGROUND:At times, ultrasound is not readily available in low resource countries in Africa for accurate determination of gestational age, so using alternative methods is pivotal during pregnancy. These assessments are used to aid the risk analysis for an infant and management strategies for premature delivery, if necessary. Currently, date of last menstrual period, fundal height measurements, and the New Ballard Score are commonly used in resource-limited settings. However, concordance of these measures is unknown for sub-Saharan Africa. We obtained data from an open-label randomized controlled trial, to assess the concordance of these alternative assessment methods. The purpose of our study was to determine the agreement between these alternative methods when used in sub-Saharan African populations. METHODS:A total of 4,390 pregnant women from Benin, Gabon, Mozambique and Tanzania were included in our analysis. The assessment methods compared were: 1) reported last menstrual period, 2) symphysis-fundal height measurement, and 3) the New Ballard Score. The Bland-Altman method and intraclass correlation coefficient (ICC) were used to test the degree of agreement. Survival range gestational age, used as an inclusion criterion for further analysis, was from 22 to 44 weeks. FINDINGS:Plots showed a lack of agreement between methods and the 95% limits of agreement too wide to be clinically useful. ICC = 0.25 indicated poor agreement. A post-hoc analysis, restricted from 32 to 42 weeks, was done to check for better agreement in this near-term population. The plots and ICC = 0.16 still confirmed poor agreement. CONCLUSION:The alternative assessments do not result in comparable outcomes and discrepancies are far beyond the clinically acceptable range. Last menstrual period should not be used as the only estimator of gestational age. In the absence of reliable early ultrasound, symphysis-fundal height measurements may be most useful during pregnancy for fetal risk assessment and the New Ballard Score after delivery as a confirmation of these estimations and for further neonatal management. However, promotion of portable ultrasound devices is required for accurate assessment of gestational age in sub-Sahara Africa.

Nasopharyngeal carriage is a precursor for pneumococcal disease and can be useful for evaluating pneumococcal conjugate vaccine (PCV) impact. We studied pre-PCV pneumococcal carriage among HIV-infected and -uninfected children in Mozambique. Between October 2012 and March 2013, we enrolled HIV-infected children age

BackgroundAnimal embryotoxicity data, and the scarcity of safety data in human pregnancies, have prevented artemisinin derivatives from being recommended for malaria treatment in the first trimester except in lifesaving circumstances. We conducted a meta-analysis of prospective observational studies comparing the risk of miscarriage, stillbirth, and major congenital anomaly (primary outcomes) among first-trimester pregnancies treated with artemisinin derivatives versus quinine or no antimalarial treatment.Methods and findingsElectronic databases including Medline, Embase, and Malaria in Pregnancy Library were searched, and investigators contacted. Five studies involving 30,618 pregnancies were included; four from sub-Saharan Africa (n = 6,666 pregnancies, six sites) and one from Thailand (n = 23,952). Antimalarial exposures were ascertained by self-report or active detection and confirmed by prescriptions, clinic cards, and outpatient registers. Cox proportional hazards models, accounting for time under observation and gestational age at enrollment, were used to calculate hazard ratios. Individual participant data (IPD) meta-analysis was used to combine the African studies, and the results were then combined with those from Thailand using aggregated data meta-analysis with a random effects model. There was no difference in the risk of miscarriage associated with the use of artemisinins anytime during the first trimester (n = 37/671) compared with quinine (n = 96/945; adjusted hazard ratio [aHR] = 0.73 [95% CI 0.44, 1.21], I2 = 0%, p = 0.228), in the risk of stillbirth (artemisinins, n = 10/654; quinine, n = 11/615; aHR = 0.29 [95% CI 0.08-1.02], p = 0.053), or in the risk of miscarriage and stillbirth combined (pregnancy loss) (aHR = 0.58 [95% CI 0.36-1.02], p = 0.099). The corresponding risks of miscarriage, stillbirth, and pregnancy loss in a sensitivity analysis restricted to artemisinin exposures during the embryo sensitive period (6-12 wk gestation) were as follows: aHR = 1.04 (95% CI 0.54-2.01), I2 = 0%, p = 0.910; aHR = 0.73 (95% CI 0.26-2.06), p = 0.551; and aHR = 0.98 (95% CI 0.52-2.04), p = 0.603. The prevalence of major congenital anomalies was similar for first-trimester artemisinin (1.5% [95% CI 0.6%-3.5%]) and quinine exposures (1.2% [95% CI 0.6%-2.4%]). Key limitations of the study include the inability to control for confounding by indication in the African studies, the paucity of data on potential confounders, the limited statistical power to detect differences in congenital anomalies, and the lack of assessment of cardiovascular defects in newborns.ConclusionsCompared to quinine, artemisinin treatment in the first trimester was not associated with an increased risk of miscarriage or stillbirth. While the data are limited, they indicate no difference in the prevalence of major congenital anomalies between treatment groups. The benefits of 3-d artemisinin combination therapy regimens to treat malaria in early pregnancy are likely to outweigh the adverse outcomes of partially treated malaria, which can occur with oral quinine because of the known poor adherence to 7-d regimens.Review registrationPROSPERO CRD42015032371.

The HIV epidemic is concentrated in sub-Saharan Africa. However, limited information exists on its impact on women and infant's health since the introduction of antiretroviral drugs in this region, where health resources are often scarce.The effect of HIV infection on maternal health, birth outcomes and infant health was analysed in two contemporary cohorts of HIV-uninfected and HIV-infected pregnant women from southern Mozambique. Pregnant women attending the first antenatal care visit were followed until one month after delivery. Antiretroviral therapy was administered based on CD4+T cell count and clinical stage. Maternal and neonatal morbidity and mortality, as well as pregnancy outcomes were assessed by mother's HIV status.A total of 1183 HIV-uninfected and 561 HIV-infected pregnant women were enrolled. HIV-infected women were more likely to have anaemia both at the first antenatal care visit and at delivery than HIV-uninfected women (71.5% versus 54.8% and 49.4% versus 40.6%, respectively, p

BackgroundLittle is known about the effects of intermittent preventive treatment of malaria in pregnancy (IPTp) on the health of sub-Saharan African infants. We have evaluated the safety of IPTp with mefloquine (MQ) compared to sulfadoxine-pyrimethamine (SP) for important infant health and developmental outcomes.Methods and findingsIn the context of a multicenter randomized controlled trial evaluating the safety and efficacy of IPTp with MQ compared to SP in pregnancy carried out in four sub-Saharan countries (Mozambique, Benin, Gabon, and Tanzania), 4,247 newborns, 2,815 born to women who received MQ and 1,432 born to women who received SP for IPTp, were followed up until 12 mo of age. Anthropometric parameters and psychomotor development were assessed at 1, 9, and 12 mo of age, and the incidence of malaria, anemia, hospital admissions, outpatient visits, and mortality were determined until 12 mo of age. No significant differences were found in the proportion of infants with stunting, underweight, wasting, and severe acute malnutrition at 1, 9, and 12 mo of age between infants born to women who were on IPTp with MQ versus SP. Except for three items evaluated at 9 mo of age, no significant differences were observed in the psychomotor development milestones assessed. Incidence of malaria, anemia, hospital admissions, outpatient visits, and mortality were similar between the two groups. Information on the outcomes at 12 mo of age was unavailable in 26% of the infants, 761 (27%) from the MQ group and 377 (26%) from the SP group. Reasons for not completing the study were death (4% of total study population), study withdrawal (6%), migration (8%), and loss to follow-up (9%).ConclusionsNo significant differences were found between IPTp with MQ and SP administered in pregnancy on infant mortality, morbidity, and nutritional outcomes. The poorer performance on certain psychomotor development milestones at 9 mo of age in children born to women in the MQ group compared to those in the SP group may deserve further studies.Trial registrationClinicalTrials.gov NCT00811421.

The objective of this qualitative study was to explore how clinical symptoms may affect adherence to antiretroviral therapy (ART) in HIV patients, and to explore factors, perceptions and attitudes related to adherence to therapy.A qualitative study was carried out in the context of the prospective cohort study "Evaluation of Immune Reconstitution Following Initiation of Highly Active Antiretroviral Treatment in Manhiça, Mozambique". In-depth Interviews were conducted twice in a sub-sample of the study cohort (51 participants), at six-month intervals.Most participants (73%) knew that AIDS is a chronic disease and that ART does not cure it. Nine participants (18%) were non-adherent at some point and two (4%) abandoned ART. All participants but five reported having symptoms after starting ART, mainly attributed to pills needing time to act and body's reaction to the treatment. In spite of the perceived severity of the symptoms, only two people reported they discontinued the treatment due to symptoms. Almost all participants reported feeling comfortable with the HIV clinic organization and procedures, but afraid of staff being hostile if they did not follow the rules or if the health worker visited their home. Family was one of the most important source of support according participants. Almost all participants with children said that a decisive factor to follow the treatment was the desire to be able to look after them.Experiencing symptoms after starting treatment was not a barrier to adherence to ART. Factors related to adherence included control measures set up by the health facility (exhaustive follow up, support, information) and family and community support. Indirect ART-related expenses did jeopardise adherence.

Monitoring the HIV epidemic in a defined population is critical for planning treatment and preventive strategies. This is especially important in sub-Saharan Africa, which harbours the highest burden of the disease.To estimate HIV incidence in adults aged 18-47 years old and to investigate spatial variations of HIV prevalence in Manhiça, a semi-rural area of southern Mozambique.Two cross-sectional community-based surveys were conducted in 2010 and 2012 to determine HIV prevalence. Individual participants were randomly selected from the demographic surveillance system in place in the area and voluntary HIV counselling and testing was offered at the household level. HIV incidence was calculated using prevalence estimates from the two sero-surveys. Each participant's household was geocoded using a global information system. The Spatial Scan Statistics programme was used to identify areas with disproportionate excess in HIV prevalence.A total of 1511 adults were tested. The estimated HIV prevalence in the community was 39.9% in 2010 and 39.7% in 2012. The overall HIV incidence was 3.6 new infections per 100 person-years at risk (PYAR) [95CI 1.56; 7.88], assuming stable epidemic conditions, and tended to be higher in women (4.9/100 PYAR [95CI 1.74; 11.85]) than in men (3.2/PYAR [95CI 1.36; 9.92]). One cluster with significant excess HIV prevalence was identified at the same geographic location in both surveys. This cluster had an HIV prevalence of 79.0% in 2010 and 52.3% in 2012.The findings of these first individually-randomised community-HIV sero-surveys conducted in Mozambique reinforce the need to combine HIV incidence estimates and research on micro geographical infection patterns to guide and consolidate effective prevention strategies.

BACKGROUND: Intermittent Preventive Treatment (IPTp) and insecticide treated nets (ITNs) are recommended malaria in pregnancy preventive interventions in sub-Saharan Africa. Despite their cost-effectiveness and seemingly straight-forward delivery mechanism, their uptake remains low. We aimed at describing perceptions of pregnant women regarding malaria and the recommended prevention interventions to understand barriers to uptake and help to improve their effectiveness. METHODS AND FINDINGS: We used mixed methods to collect data among 85 pregnant women from a rural area of Southern Mozambique. Information was obtained through observations, in-depth interviews, and focused ethnographic exercises (Free-listing and Pairwise comparisons). Thematic analysis was performed on qualitative data. Data from focused ethnographic exercises were summarized into frequency distribution tables and matrices. Malaria was not viewed as a threat to pregnancy. Participants were not fully aware of malaria- associated adverse maternal and birth outcomes. ITNs were the most preferred and used malaria preventive intervention, while IPTp fell between second and third. Indoor Residual Spraying (IRS) was the least preferred intervention. CONCLUSIONS: Low awareness of the risks and adverse consequences of malaria in pregnancy did not seem to affect acceptability or uptake to the different malaria preventive interventions in the same manner. Perceived convenience, the delivery approach, and type of provider were the key factors. Pregnant women, through antenatal care (ANC) services, can be the vehicles of ITN distribution in the communities to maximise overall ITN coverage. There is a need to improve knowledge about neonatal health and malaria to improve uptake of interventions delivered through channels other than the health facility.

BACKGROUND: Human milk and infant gut microbiota are essential for the immune system maturation and protection against infections. There is scarce information on the microbiological composition of breast milk in general, and none from developing countries. The objective of the study was to characterize the breast milk and gut microbiota from mothers and infants from southern Mozambique, where infections and breastfeeding are prevalent. METHODS: A community-based study was undertaken among 121 pairs of women and infants. Breast milk and infant's faeces were analyzed by bacterial culture and molecular methods. Breast milk samples were screened for HIV RNA by RT-PCR. RESULTS: The most frequent bacterial groups isolated by culture media in breast milk were Staphylococci (96.4%), Streptococci (92.7%) and Lactobacilli (56.4%). HIV RNA was detected in 24% of the samples. Staphylococcus hominis, S. aureus, and S.parasanguis were more frequently isolated in infants ≤14 days of life. Women on exclusive breastfeeding presented higher proportion of S. parasanguis in breast milk than those on mixed infant feeding (36.4% versus 11.1%, p = 0.035). Bacterial diversity (mean number of bacterial species isolated by sample: 10.4 versus 8.5; p = 0.004) and the frequency of Lactobacillus spp (75.9% versus 36%, p = 0.003) were higher in the specimens with HIV RNA than in those without it. The main bacterial groups found in infant's faeces were Bifidobacterium, Streptococci and Enterococci. CONCLUSIONS: Women with HIV RNA in breast milk had a different pattern of microbiological composition, suggesting specific immunopathological phenomena in HIV-infected women. Both breast milk and faecal microbiota composition varied with lactation period, which might be related to changes in the type of feeding over time and/or in the milk's biochemical characteristics. These findings provide insights into interactions between commensal bacteria and HIV infection in human milk and the role of these bacteria in mucosal protection against infections in breastfed infants.

The pre-erythrocytic malaria vaccine RTS,S/AS02A has shown to confer protection against clinical malaria for at least 21 months in a trial in Mozambican children. Efficacy varied between different endpoints, such as parasitaemia or clinical malaria; however the underlying mechanisms that determine efficacy and its duration remain unknown. We performed a new, exploratory analysis to explore differences in the duration of protection among participants to better understand the protection afforded by RTS,S.The study was a Phase IIb double-blind, randomized controlled trial in 2022 children aged 1 to 4 years. The trial was designed with two cohorts to estimate vaccine efficacy against two different endpoints: clinical malaria (cohort 1) and infection (cohort 2). Participants were randomly allocated to receive three doses of RTS,S/AS02A or control vaccines. We did a retrospective, unplanned sub-analysis of cohort 2 data using information collected for safety through the health facility-based passive case detection system. Vaccine efficacy against clinical malaria was estimated over the first six-month surveillance period (double-blind phase) and over the following 12 months (single-blind phase), and analysis was per-protocol. Adjusted vaccine efficacy against first clinical malaria episodes in cohort 2 was of 35.4% (95% CI 4.5-56.3; p = 0.029) over the double-blind phase and of 9.0% (-30.6-36.6; p = 0.609) during the single-blind phase.Contrary to observations in cohort 1, where efficacy against clinical malaria did not wane over time, in cohort 2 the efficacy decreases with time. We hypothesize that this reduced duration of protection is a result of the early diagnosis and treatment of infections in cohort 2 participants, preventing sufficient exposure to asexual-stage antigens. On the other hand, the long-term protection against clinical disease observed in cohort 1 may be a consequence of a prolonged exposure to low-dose blood-stage asexual parasitaemia.ClinicalTrials.gov NCT00197041.

Abstract Background Monitoring HIV infection estimates is critical to guide health interventions and assess their impact, especially in highly vulnerable groups to the infection such as African pregnant women. This study describes the trends of HIV infection over eleven years in women attending selected antenatal care (ANC) clinics from southern Mozambique. Methods We performed a secondary analysis of data registered at the ANC clinic of the Manhiça District Hospital and from the Ministry of Health's HIV National Program Registry between 2010 and 2021. HIV incidence was calculated using prevalence estimates. HIV incidence trends over time were obtained by fitting splines regression model. Results Data from 21,810 pregnant women were included in the analysis. Overall HIV prevalence was 29.3% (95% CI: 28.7–29.9), with a reduction from 28.2% (95% CI: 25.6–30.8) in 2010 to 21.7% (95% CI: 19.8–23.6) in 2021, except for a peak in prevalence (35.3%, 95% CI: 30.1–40.8) in 2016. Over the study period, by maternal age group, the largest reduction in HIV prevalence was in the 15–20 year-old group [62% reduction, from 14.3% (95% CI 10.8–18.4) to 5.3% (95% CI: 3.6–7.5)], followed by the 20–25 year old group [43% reduction, from 29.0% (95% CI: 24.2–34.5) to 16.6% (95% CI: 13.6–19.8)] and the 25–30 year old group [13% reduction, from 36.9% (95% CI: 31.0–43.1) to 32.0% (95% CI: 27.3–37.0)] (p

Objectives: Malaria is still one of the main reasons for hospitalization in children living in sub-Saharan Africa. Rapid risk stratification at admission is essential for optimal medical care and improved prognosis. Whereas coma, deep breathing, and, to a lesser degree, severe anemia are established predictors of malaria-related death, the value of assessing prostration for risk stratification is less certain. Methods: Here we used a retrospective multi-center analysis comprising over 33,000 hospitalized children from four large studies, including two observational studies from the Severe Malaria in African Children network, a randomized controlled treatment study, and the phase-3-clinical RTS,S-malaria vaccine trial, to evaluate known risk factors of mortality and with a specific emphasis on the role of prostration. Results: Despite comparable age profiles of the participants, we found significant inter- and intra-study variation in the incidence of fatal malaria as well as in the derived risk ratios associated with the four risk factors: coma, deep breathing, anemia, and prostration. Despite pronounced variations, prostration was significantly associated with an increased risk of mortality (P

Abstract Mozambique is one of the four African countries which account for over half of all malaria deaths worldwide, yet little is known about the parasite genetic structure in that country. We performed P. falciparum amplicon and whole genome sequencing on 2251 malaria-infected blood samples collected in 2015 and 2018 in seven provinces of Mozambique to genotype antimalarial resistance markers and interrogate parasite population structure using genome-wide microhaplotyes. Here we show that the only resistance-associated markers observed at frequencies above 5% were pfmdr1-184F (59%), pfdhfr-51I/59 R/108 N (99%) and pfdhps-437G/540E (89%). The frequency of pfdhfr/pfdhps quintuple mutants associated with sulfadoxine-pyrimethamine resistance increased from 80% in 2015 to 89% in 2018 (p

BackgroundSeroprevalence studies are an alternative approach to estimating the extent of transmission of SARS-CoV-2 and the evolution of the pandemic in different geographical settings. We aimed to determine the SARS-CoV-2 seroprevalence from March 2020 to March 2022 in a rural and urban setting in Kilifi County, Kenya.MethodsWe obtained representative random samples of stored serum from a pregnancy cohort study for the period March 2020 to March 2022 and tested for antibodies against the spike protein using a qualitative SARS-CoV-2 ELISA kit (Wantai, total antibodies). All positive samples were retested for anti-SARS-CoV-2 anti-nucleocapsid antibodies (Euroimmun, ELISA kits, NCP, qualitative, IgG) and anti-spike protein antibodies (Euroimmun, ELISA kits, QuantiVac; quantitative, IgG).ResultsA total of 2,495 (of 4,703 available) samples were tested. There was an overall trend of increasing seropositivity from a low of 0% [95% CI 0–0.06] in March 2020 to a high of 89.4% [95% CI 83.36–93.82] in Feb 2022. Of the Wantai test-positive samples, 59.7% (95% CI 57.06–62.34) tested positive by the Euroimmun anti-SARS-CoV-2 NCP test and 75.9% (95% CI 73.55–78.17) tested positive by the Euroimmun anti-SARS-CoV-2 QuantiVac test. No differences were observed between the urban and rural hospital but villages adjacent to the major highway traversing the study area had a higher seroprevalence.ConclusionAnti-SARS-CoV-2 seroprevalence rose rapidly, with most of the population exposed to SARS-CoV-2 within 23 months of the first cases. The high cumulative seroprevalence suggests greater population exposure to SARS-CoV-2 than that reported from surveillance data.

BackgroundMalaria is among the top causes of death in adolescent girls (10 to 19 years) globally. Adolescent motherhood is associated with increased risk of adverse maternal and neonatal outcomes. The interaction of malaria, adolescence, and pregnancy is especially relevant in malaria endemic areas, where rates of adolescent pregnancy are high. However, data on burden of malaria among adolescent girls are limited. This study aimed at investigating whether adolescent girls were at a greater risk of experiencing malaria-related outcomes in pregnancy-parasitaemia and clinical disease-than adult women.Methods and findingsAn individual secondary participant-level meta-analysis was conducted using data from 5,804 pregnant women participating in 2 malaria prevention clinical trials in Benin, Gabon, Kenya, Mozambique, and Tanzania between 2009 and 2014. Of the sample, 1,201 participants were adolescent girls with a mean age of 17.5 years (standard deviation (SD) 1.3) and 886 (73.8%) of them primigravidae. Among the 4,603 adult women with mean age of 27.0 years (SD 5.4), 595 (12.9%) were primigravidae. Mean gestational age at enrolment was 20.2 weeks (SD 5.2) and 1,069 (18.4%) participants were HIV-infected. Women were followed monthly until the postpartum visit (1 month to 6 weeks after delivery). This study considered outcomes including clinical episodes during pregnancy, peripheral parasitaemia at delivery, and placental malaria. A 2-stage meta-analysis approach was followed by pooling single multivariable regression results into standard DerSimonian-Laird random-effects models. Adolescent girls were more likely than adult women to present with clinical malaria during pregnancy (incidence risk ratio (IRR) 1.70, 95% confidence interval (CI) 1.20; 2.39, p-value = 0.003, I2 = 0.0%, N = 4,092), peripheral parasitaemia at delivery (odds ratio (OR) 2.28, 95% CI 1.46; 3.55, p-value < 0.001, I2 = 0.0%, N = 3,977), and placental infection (OR 1.97, 95% CI 1.31; 2.98, p-value = 0.001, I2 = 1.4%, N = 4,797). Similar associations were observed among the subgroup of HIV-uninfected participants: IRR 1.72 (95% CI 1.22; 2.45, p-value = 0.002, I2 = 0.0%, N = 3,531) for clinical malaria episodes, OR 2.39 (95% CI 1.49; 3.86, p-value < 0.001, I2 = 0.0%, N = 3,053) for peripheral parasitaemia, and OR 1.88 (95% CI 1.06 to 3.33, p-value = 0.03, I2 = 34.9%, N = 3,847) for placental malaria. Among HIV-infected subgroups statistically significant associations were not observed. Similar associations were found in the subgroup analysis by gravidity. The small sample size and outcome prevalence in specific countries limited the inclusion of some countries in the meta-analysis. Furthermore, peripheral parasitaemia and placental malaria presented a considerable level of missing data-12.6% and 18.2% of participants had missing data on those outcomes, respectively. Given the original scope of the clinical trials, asymptomatic malaria infection was only assessed at the end of pregnancy through peripheral and placental parasitaemia.ConclusionsIn this study, we observed that adolescent girls in sub-Saharan Africa (SSA) are more prone to experience clinical malaria episodes during pregnancy and have peripheral malaria and placental infection at delivery than adult women. Moreover, to the best of our knowledge, for the first time this study disaggregates figures and stratifies analyses by HIV infection. Similar associations were found for both HIV-infected and uninfected women, although those for HIV-infected participants were not statistically significant. Our finding suggests that adolescent girls may benefit from targeted malaria prevention strategies even before they become pregnant.