Applying the photovoice method with adolescents in mining areas in rural Mozambique: critical reflections and lessons learned.

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 adolescents' 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.

Sustained clinical benefit of malaria chemoprevention with sulfadoxine-pyrimethamine (SP) in pregnant women in a region with high SP resistance markers.

OBJECTIVE: The effectiveness of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) is threatened by increasing SP-resistance in Africa. We assessed the level of SP-resistance markers, and the clinical and parasitological effectiveness of IPTp-SP in southern Mozambique. METHODS: P. falciparum infection, antimalarial antibodies and dhfr/dhps SP-resistance mutants were detected by quantitative polymerase chain reaction (qPCR), suspension array technology and targeted deep sequencing, respectively, among 4016 HIV-negative women in Maputo province (2016-2019). Univariate and multivariate regression models were used to assess the association between taking the recommended three or more IPTp-SP doses (IPTp3+) and parasitological and clinical outcomes. RESULTS: 84.3% (3385/4016) women received three or more IPTp-SP doses. The prevalence of quintuple mutants at first antenatal care (ANC) visit was 94.2%. IPTp3+ was associated with a higher clearance rate of qPCR-detected infections from first ANC visit to delivery (adjusted odds ratio [aOR]=5.9, 95% CI: 1.5-33.3; p = 0.012), lower seroprevalence at delivery of antibodies against the pregnancy-specific antigen VAR2CSADBL34 (aOR=0.72, 95% CI: 0.54-0.95; p = 0.022), and lower prevalence of low birth weight deliveries (aOR: 0.61, 95% CI: 0.41-0.90; p = 0.013). CONCLUSION: A sustained parasitological effect of IPTp-SP contributes to the clinical effectiveness of IPTp3+ in areas with high prevalence of SP-resistance markers.

Genomic malaria surveillance of antenatal care users detects reduced transmission following elimination interventions in Mozambique.

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.

Detecting temporal and spatial malaria patterns from first antenatal care visits

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<1.1), with a 2-3 months lag. Only at rapid diagnostic test detection limits at moderate-to-high transmission, did multigravidae show lower rates than children (PCC = 0.61, 95%CI[-0.12-0.94]). Seroprevalence against the pregnancy-specific antigen VAR2CSA reflected declining malaria trends (PCC = 0.74, 95%CI[0.24-0.77]). 60% (9/15) of hotspots detected from health facility data (n = 6662) using a novel hotspot detector, EpiFRIenDs, were also identified with ANC data (n = 3616). Taken together, we show that ANC-based malaria surveillance offers contemporary information on temporal trends and geographic distribution of malaria burden in the community

Targeted and whole-genome sequencing reveal a north-south divide in P. falciparum drug resistance markers and genetic structure in Mozambique

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 < 0.001), with a lower expected heterozygosity and higher relatedness of microhaplotypes surrounding pfdhps mutants than wild-type parasites suggestive of recent selection. pfdhfr/pfdhps quintuple mutants also increased from 72% in the north to 95% in the south (2018; p < 0.001). This resistance gradient was accompanied by a concentration of mutations at pfdhps-436 (17%) in the north, a south-to-north increase in the genetic complexity of P. falciparum infections (p = 0.001) and a microhaplotype signature of regional differentiation. The parasite population structure identified here offers insights to guide antimalarial interventions and epidemiological surveys.

Burden of malaria in pregnancy among adolescent girls compared to adult women in 5 sub-Saharan African countries: A secondary individual participant data meta-analysis of 2 clinical trials

Malaria 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. An 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.

Factors associated with use of insecticide-treated net for malaria prevention in Manica District, Mozambique: a community-based cross-sectional survey

Background: Insecticide-treated net (ITN) use is crucial for preventing malaria infection. Despite significant improvements in ITN access and use over the past two decades, many malaria-endemic countries in sub-Saharan Africa have not yet reached global targets for universal coverage of ITNs. To reduce the gaps in ITN use, it is important to understand the factors associated with ITN use. The goal of this analysis was to determine the factors associated with ITN use in Manica District, Mozambique. Methods: A cross-sectional community-based survey was conducted from October to November 2019. Households were randomly selected, and all members of selected households were eligible to participate. Data on socio-demographic characteristics, housing construction and the ownership, use and characteristics of ITNs were collected using structured questionnaires. Factors independently associated with ITN use were identified using generalized estimating equations multivariate logistic regression. Results: Of the 302 households surveyed, 209 (69.2%) owned at least one ITN and 176 (58.3%) had one ITN for every two household members. The multivariate analysis indicated that the odds of ITN use was significantly lower among individuals in households with 3 or more members. However, the odds of ITN use was significantly higher among older age groups, poorer households, and as the number of ITNs in a household increased. Conclusions: The findings of this analysis highlight the need for behaviour change communication strategies targeting young people and ITN distribution campaigns targeting larger households to increase ITN ownership, thereby improving ITN use in Manica District.

Adolescent, Pregnant, and HIV-Infected: Risk of Adverse Pregnancy and Perinatal Outcomes in Young Women from Southern Mozambique

Sub-Saharan Africa concentrates the burden of HIV and the highest adolescent fertility rates. However, there is limited information about the impact of the interaction between adolescence and HIV infection on maternal health in the region. Data collected prospectively from three clinical trials conducted between 2003 and 2014 were analysed to evaluate the association between age, HIV infection, and their interaction, with the risk of maternal morbidity and adverse pregnancy and perinatal outcomes in women from southern Mozambique. Logistic regression and negative binomial models were used. A total of 2352 women were included in the analyses; 31% were adolescents (≤19 years) and 29% HIV-infected women. The effect of age on maternal morbidity and pregnancy and perinatal adverse outcomes was not modified by HIV status. Adolescence was associated with an increased incidence of hospital admissions (IRR 0.55, 95%CI 0.37-0.80 for women 20-24 years; IRR 0.60, 95%CI 0.42-0.85 for women >25 years compared to adolescents; p-value < 0.01) and outpatient visits (IRR 0.86, 95%CI 0.71-1.04; IRR 0.76, 95%CI 0.63-0.92; p-value = 0.02), and an increased likelihood of having a small-for-gestational age newborn (OR 0.50, 95%CI 0.38-0.65; OR 0.43, 95%CI 0.34-0.56; p-value < 0.001), a low birthweight (OR 0.40, 95%CI 0.27-0.59; OR 0.37, 95%CI 0.26-0.53; p-value <0.001) and a premature birth (OR 0.42, 95%CI 0.24-0.72; OR 0.51, 95%CI 0.32-0.82; p-value < 0.01). Adolescence was associated with an increased risk of poor morbidity, pregnancy and perinatal outcomes, irrespective of HIV infection. In addition to provision of a specific maternity care package for this vulnerable group interventions are imperative to prevent adolescent pregnancy.

Community acceptability to antimalarial mass drug administrations in Magude district, Southern Mozambique: A mixed methods study

Background This study aimed to capture the acceptability prior to, during and after the implementation of the first year of MDA rounds conducted under the Magude project, a malaria elimination project in southern Mozambique. Methods This was amixed-methods study, consisting of focus group discussions (FGDs) prior to the implementation of MDA rounds (September 2015), non-participant observations (NPOs) conducted during the MDA rounds (November 2015 ­beginning of February 2016), and semi-structured interviews (SSIs) after the second round (end of February 2016). Community leaders, women in reproductive age, general members of the community, traditional healers and health professionals were recruited to capture the opinions of all representing key membersofthecommunity. A generic outline of nodes and codes was designed to analyze FGDsandSSIseparately. Qualitative and quantitative NPO information was analyzed following a content analysis approach. Findings 222participants took part in the FGDs (n = 154), and SSIs (n = 68); and 318 household visits during the MDAunderwent NPOs.Thecommunityengagement campaign emerged throughout the study stages as a crucial factor for the acceptability of MDAs. Acceptability wasalso fostered by the community's general will to cooperate in any government-led activity that would reduce malaria burden, the appropriate behavior and knowledge of field workers, or the fact that the intervention was available free of charge to all. Absenteeism of heads of households was identified as the main barrier for the success of the campaign. The most commonly reported factors that negatively affected acceptability were the fear of adverse events, rumors of deaths, being unable to drink alcohol while taking DHAp, or the fear to take DHAp while in anti-retroviral treatment. Pregnancy testing and malaria testing were generally well accepted by the community. Conclusion Magude's community generally accepted the first and second antimalarial MDA rounds, and the procedures associated to the intervention. Future implementation of antimalarial MDAs in southern Mozambique should focus on locally adapted strategies that engage the community to minimize absenteeism and refusals to the intervention.

Assessment of the Feasibility, Acceptability, and Impact of Implementing Seasonal Malaria Chemoprevention in Nampula Province, Mozambique: Protocol for a Hybrid Effectiveness-Implementation Study

Background Malaria is a significant cause of morbidity and mortality in children aged under 5 years in Mozambique. The World Health Organization recommends seasonal malaria chemoprevention (SMC), the administration of four monthly courses of sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ), to children aged 3-59 months during rainy season. However, as resistance to SP is widespread in East and Southern Africa, SMC has so far only been implemented across the Sahel in West Africa. Objective This protocol describes the first phase of a pilot project that aims to assess the protective effect of SP and AQ when used for SMC and investigate the levels of molecular markers of resistance of Plasmodium falciparum to antimalarial medicines in the study districts. In addition, it is important to understand whether SMC is a feasible and acceptable intervention in the context of Nampula Province, Mozambique. Methods This study will adopt a hybrid effectiveness-implementation design to conduct a mixed methods evaluation with six objectives: a molecular marker study, a nonrandomized controlled trial, an analysis of reported malaria morbidity indicators, a documentation exercise of the contextual SMC adaptation, an acceptability and feasibility assessment, and a coverage and quality assessment. Results Ethical approval for this study was granted by the Mozambican Ministry of Health National Bioethics Committee on September 15, 2020. Data collection began in October 2020, and data analysis is expected to be completed by August 2021. Conclusions This research will make a unique contribution to our understanding of whether the combination of SP and AQ, when used for SMC, can confer a protective effect against malaria in children aged 3-59 months in a region where malaria transmission is seasonal and SP resistance is expected to be high. If the project is successful, subsequent phases are expected to provide a more comprehensive assessment of the effectiveness and sustainability of SMCs.

Feasibility of task-sharing with community health workers for the identification, emergency management and referral of women with pre-eclampsia, in Mozambique

Background Maternal mortality is an important public health problem in low-income countries. Delays in reaching health facilities and insufficient health care professionals call for innovative community-level solutions. There is limited evidence on the role of community health workers in the management of pregnancy complications. This study aimed to describe the feasibility of task-sharing the initial screening and initiation of obstetric emergency care for pre-eclampsia/eclampsia from the primary healthcare providers to community health workers in Mozambique and document healthcare facility preparedness to respond to referrals. Method The study took place in Maputo and Gaza Provinces in southern Mozambique and aimed to inform the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomized controlled trial. This was a mixed-methods study. The quantitative data was collected through self-administered questionnaires completed by community health workers and a health facility survey; this data was analysed using Stata v13. The qualitative data was collected through focus group discussions and in-depth interviews with various community groups, health care providers, and policymakers. All discussions were audio-recorded and transcribed verbatim prior to thematic analysis using QSR NVivo 10. Data collection was complemented by reviewing existing documents regarding maternal health and community health worker policies, guidelines, reports and manuals. Results Community health workers in Mozambique were trained to identify the basic danger signs of pregnancy; however, they have not been trained to manage obstetric emergencies. Furthermore, barriers at health facilities were identified, including lack of equipment, shortage of supervisors, and irregular drug availability. All primary and the majority of secondary-level facilities (57%) do not provide blood transfusions or have surgical capacity, and thus such cases must be referred to the tertiary-level. Although most healthcare facilities (96%) had access to an ambulance for referrals, no transport was available from the community to the healthcare facility. Conclusions This study showed that task-sharing for screening and pre-referral management of pre-eclampsia and eclampsia were deemed feasible and acceptable at the community-level, but an effort should be in place to address challenges at the health system level.

In vivo efficacy and safety of artemether-lumefantrine and amodiaquine-artesunate for uncomplicated Plasmodium falciparum malaria in Mozambique, 2018

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

Reduced Placental Transfer of Antibodies Against a Wide Range of Microbial and Vaccine Antigens in HIV-Infected Women in Mozambique

Transplacental transfer of antibodies is essential for conferring protection in newborns against infectious diseases. We assessed the impact of different factors, including gestational age and maternal infections such as HIV and malaria, on the efficiency of cord blood levels and placental transfer of IgG subclasses. We measured total IgG and IgG subclasses by quantitative suspension array technology against 14 pathogens and vaccine antigens, including targets of maternal immunization, in 341 delivering HIV-uninfected and HIV-infected mother-infant pairs from southern Mozambique. We analyzed the association of maternal HIV infection, Plasmodium falciparum exposure, maternal variables and pregnancy outcomes on cord antibody levels and transplacental transfer. Our results show that maternal antibody levels were the main determinant of cord antibody levels. Univariable and multivariable analysis showed that HIV reduced the placental transfer and cord levels of IgG and IgG1 principally, but also IgG2 to half of the antigens tested. P. falciparum exposure and prematurity were negatively associated with cord antibody levels and placental transfer, but this was antigen-subclass dependent. Our findings suggest that lower maternally transferred antibodies may underlie increased susceptibility to infections of HIV-exposed infants. This could affect efficacy of maternal vaccination, especially in sub-Saharan Africa, where there is a high prevalence of HIV, malaria and unfavorable environmental factors.

In vivo efficacy and safety of artemetherlumefantrine and amodiaquine­artesunate for uncomplicated Plasmodium falciparum malaria in Mozambique, 2018

Background: Artemisinin-based combination therapy (ACT) has been the recommended first-line treatment for uncomplicated malaria in Mozambique since 2006, with artemether­lumefantrine (AL) and amodiaquine­artesunate (AS­AQ) 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 (2000­200,000 parasites/µl) were enrolled between February and September of 2018, assigned to either an AL or AS­AQ 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 AS­AQ arms, respectively. Of these, 9.5% (35/368) and 5.1% (14/273) were lost to follow-up in the AL and AS­AQ arms, respectively. There were 48 and 3 recurrent malaria infections (late clinical and late parasitological failures) in the AL and AS­AQ arms, respectively. The day 28 uncorrected efficacy was 85.6% (95% confidence interval (CI) 81.3­89.2%) for AL and 98.8% (95% CI 96.7­99.8%) for AS­AQ, whereas day 28 PCR-corrected efficacy was 97.9% (95% CI 95.6­99.2%) for AL and 99.6% (95% CI 97.9­100%) for AS­AQ. Molecular testing confirmed that 87.4% (42/48) and 33.3% (1/3) of participants with a recurrent malaria infection in the AL and AS­AQ 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 AS­AQ 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.

Reduced Placental Transfer of Antibodies Against a Wide Range of Microbial and Vaccine Antigens in HIV-Infected Women in Mozambique

Transplacental transfer of antibodies is essential for conferring protection in newborns against infectious diseases. We assessed the impact of different factors, including gestational age and maternal infections such as HIV and malaria, on the efficiency of cord blood levels and placental transfer of IgG subclasses. We measured total IgG and IgG subclasses by quantitative suspension array technology against 14 pathogens and vaccine antigens, including targets of maternal immunization, in 341 delivering HIV-uninfected and HIV-infected mother-infant pairs from southern Mozambique. We analyzed the association of maternal HIV infection, Plasmodium falciparum exposure, maternal variables and pregnancy outcomes on cord antibody levels and transplacental transfer. Our results show that maternal antibody levels were the main determinant of cord antibody levels. Univariable and multivariable analysis showed that HIV reduced the placental transfer and cord levels of IgG and IgG1 principally, but also IgG2 to half of the antigens tested. P. falciparum exposure and prematurity were negatively associated with cord antibody levels and placental transfer, but this was antigen-subclass dependent. Our findings suggest that lower maternally transferred antibodies may underlie increased susceptibility to infections of HIV-exposed infants. This could affect efficacy of maternal vaccination, especially in sub-Saharan Africa, where there is a high prevalence of HIV, malaria and unfavorable environmental factors

HIV infection and placental malaria reduce maternal transfer of multiple antimalarial antibodies in Mozambican women / HIV infection and placental malaria reduce maternal transfer of multiple antimalarial antibodies in Mozambican women

Maternal Plasmodium falciparum-specific antibodies may contribute to protect infants against severe malaria. Our main objective was to evaluate the impact of maternal HIV infection and placental malaria on the cord blood levels and efficiency of placental transfer of IgG and IgG subclasses. Methods: In a cohort of 341 delivering HIV-negative and HIV-positive mothers from southern Mozambique, we measured total IgG and IgG subclasses in maternal and cord blood pairs by quantitative suspension array technology against eight P. falciparum antigens: Duffy-binding like domains 3-4 of VAR2CSA from the erythrocyte membrane protein 1, erythrocyte-binding antigen 140, exported protein 1 (EXP1), merozoite surface proteins 1, 2 and 5, and reticulocyte-binding-homologue-4.2 (Rh4.2). We performed univariable and multivariable regression models to assess the association of maternal HIV infection, placental malaria, maternal variables and pregnancy outcomes on cord antibody levels and antibody transplacental transfer. Results: Maternal antibody levels were the main determinants of cord antibody levels. HIV infection and placental malaria reduced the transfer and cord levels of IgG and IgG1, and this was antigen-dependent. Low birth weight was associated with an increase of IgG2 in cord against EXP1 and Rh4.2. Conclusions: We found lower maternally transferred antibodies in HIV-exposed infants and those born from mothers with placental malaria, which may underlie increased susceptibility to malaria in these children.

Minimally Invasive Tissue Sampling: A Tool to Guide Efforts to Reduce AIDS-Related Mortality in Resource-Limited Settings

Available information on the causes of death among people living with human immunodeficiency virus (PLHIV) in low- and middle-income countries (LMICs) remains scarce. We aimed to provide data on causes of death in PLHIV from two LMICs, Brazil and Mozambique, to assess the impact of clinical misdiagnosis on mortality rates and to evaluate the accuracy of minimally invasive tissue sampling (MITS) in determining the cause of death in PLHIV. Methods: We performed coupled MITS and complete autopsy on 164 deceased PLHIV (18 children, 36 maternal deaths, and 110 adults). HIV antibody levels and HIV RNA viral loads were determined from postmortem serum samples. Results: Tuberculosis (22.7%), toxoplasmosis (13.9%), bacterial infections (13.9%), and cryptococcosis (10.9%) were the leading causes of death in adults. In maternal deaths, tuberculosis (13.9%), bacterial infections (13.9%), cryptococcosis (11.1%), and cerebral malaria (8.3%) were the most frequent infections, whereas viral infections, particularly cytomegalovirus (38.9%), bacterial infections (27.8%), pneumocystosis (11.1%), and HIV-associated malignant neoplasms (11.1%) were the leading cause among children. Agreement between the MITS and the complete autopsy was 100% in children, 91% in adults, and 78% in maternal deaths. The MITS correctly identified the microorganism causing death in 89% of cases. Conclusions: Postmortem studies provide highly granular data on the causes of death in PLHIV. The inaccuracy of clinical diagnosis may play a significant role in the high mortality rates observed among PLHIV in LMICs. MITS might be helpful in monitoring the causes of death in PLHIV and in highlighting the gaps in the management of the infections.

Challenges and needs for social behavioural research and community engagement activities during the COVID-19 pandemic in rural Mozambique

After the Ebola outbreaks the world is again facing a challenge in which human behaviours and contact history play crucial roles in determining the trends in disease spreading within and across communities. With the onset of the recent coronavirus disease (COVID-19) pandemic, several issues related to conducting social behavioural sciences research and related community engagement activities arise, especially in rural areas of low-income countries, where the coverage of information and communication technologies (ICTs) is limited and their application on field-based research would imply a biased selection of relatively more privileged minorities with access to on-line and other communication platforms not requiring physical contact. This article enumerates and discusses the different technical challenges that social behavioural sciences research and community engagement activities face in times of public health emergencies caused by pandemics such as COVID-19. It also highlights the possibility of using alternative approaches to maintain the engagement with members of rural communities in research and social action activities, as well as the ethical challenges arising from such approaches.

Demographic and health community-based surveys to inform a malaria elimination project in magude district, southern Mozambique

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.

A multiphase program for malaria elimination in southern Mozambique (the Magude project): A before-after study

Background: Malaria eradication remains the long-term vision of the World Health Organization (WHO). However, whether malaria elimination is feasible in areas of stable transmission in sub-Saharan Africa with currently available tools remains a subject of debate. This study aimed to evaluate a multiphased malaria elimination project to interrupt Plasmodium falciparum malaria transmission in a rural district of southern Mozambique. Methods and findings: A before-after study was conducted between 2015 and 2018 in the district of Magude, with 48,448 residents living in 10,965 households. Building on an enhanced surveillance system, two rounds of mass drug administrations (MDAs) per year over two years (phase I, August 2015-2017), followed by one year of reactive focal mass drug administrations (rfMDAs) (phase II, September 2017-June 2018) were deployed with annual indoor residual spraying (IRS), programmatically distributed long-lasting insecticidal nets (LLINs), and standard case management. The four MDA rounds covered 58%-72% of the population, and annual IRS reported coverage was >70%. Yearly parasite surveys and routine surveillance data were used to monitor the primary outcomes of the study-malaria prevalence and incidence-at baseline and annually since the onset of the project. Parasite prevalence by rapid diagnostic test (RDT) declined from 9.1% (95% confidence interval [CI] 7.0-11.8) in May 2015 to 2.6% (95% CI 2.0-3.4), representing a 71.3% (95% CI 71.1-71.4, p < 0.001) reduction after phase I, and to 1.4% (95% CI 0.9-2.2) after phase II. This represented an 84.7% (95% CI 81.4-87.4, p < 0.001) overall reduction in all-age prevalence. Case incidence fell from 195 to 75 cases per 1,000 during phase I (61.5% reduction) and to 67 per 1,000 during phase II (65.6% overall reduction). Interrupted time series (ITS) analysis was used to estimate the level and trend change in malaria cases associated with the set of project interventions and the number of cases averted. Phase I interventions were associated with a significant immediate reduction in cases of 69.1% (95% CI 57.5-77.6, p < 0.001). Phase II interventions were not associated with a level or trend change. An estimated 76.7% of expected cases were averted throughout the project (38,369 cases averted of 50,005 expected). One malaria-associated inpatient death was observed during the study period. There were 277 mild adverse events (AEs) recorded through the passive pharmacovigilance system during the four MDA rounds. One serious adverse event (SAE) that resulted in death was potentially related to the drug. The study was limited by the incomplete coverage of interventions, the quality of the routine and cross-sectional data collected, and the restricted accuracy of ITS analysis with a short...