Close Proximity to Mining Is Associated with Increased Prevalence of the Drug Resistance-Associated Mutation dhps540E in Eastern Democratic Republic of the Congo.

Increasing sulfadoxine-pyrimethamine (SP) resistance in the Democratic Republic of the Congo (DRC) has threatened its use for prevention of malaria in one of the most malarious countries in the world. Using geographic information on mining operations in the DRC and genetic data on SP drug resistance markers from the 2013-2014 Demographic and Health Surveys, we evaluated associations between close residence to mining and the presence of mutations conferring resistance to sulfadoxine. Close residential proximity to mining was associated with increased prevalence odds ratio (POR) of the dhps540E mutation (POR: 2.11, 95% uncertainty interval: 1.15-3.96) with adjustments for confounding variables and space. Our findings indicate that exposure to mining is associated with increased presence of an antimalarial drug resistance haplotype that threatens effective use of SP for vulnerable populations. Areas actively engaged in mining could be considered for interventions to reduce the spread of emerging drug resistance in the DRC.

Junk food use and neurodevelopmental and growth outcomes in infants in low-resource settings.

Introduction: Feeding infants a sub-optimal diet deprives them of critical nutrients for their physical and cognitive development. The objective of this study is to describe the intake of foods of low nutritional value (junk foods) and identify the association with growth and developmental outcomes in infants up to 18 months in low-resource settings. Methods: This is a secondary analysis of data from an iron-rich complementary foods (meat versus fortified cereal) randomized clinical trial on nutrition conducted in low-resource settings in four low- and middle-income countries (Democratic Republic of the Congo, Guatemala, Pakistan, and Zambia). Mothers in both study arms received nutritional messages on the importance of exclusive breastfeeding up to 6 months with continued breastfeeding up to at least 12 months. This study was designed to identify the socio-demographic predictors of feeding infants' complementary foods of low nutritional value (junk foods) and to assess the associations between prevalence of junk food use with neurodevelopment (assessed with the Bayley Scales of Infant Development II) and growth at 18 months. Results: 1,231 infants were enrolled, and 1,062 (86%) completed the study. Junk food feeding was more common in Guatemala, Pakistan, and Zambia than in the Democratic Republic of Congo. 7% of the infants were fed junk foods at 6 months which increased to 70% at 12 months. Non-exclusive breastfeeding at 6 months, higher maternal body mass index, more years of maternal and paternal education, and higher socioeconomic status were associated with feeding junk food. Prevalence of junk foods use was not associated with adverse neurodevelopmental or growth outcomes. Conclusion: The frequency of consumption of junk food was high in these low-resource settings but was not associated with adverse neurodevelopment or growth over the study period.

Incidence of possible serious bacterial infection in young infants in the three high-burden countries of the Democratic Republic of the Congo, Kenya, and Nigeria: A secondary analysis of a large, multi-country, multi-centre clinical trial.

Background: Neonatal infections are a major public health concern worldwide, particularly in low- and middle-income countries, where most of the infection-related deaths in under-five children occur. Sub-Saharan Africa has the highest mortality rates, but there is a lack of data on the incidence of sepsis from this region, hindering efforts to improve child survival. We aimed to determine the incidence of possible serious bacterial infection (PSBI) in young infants in three high-burden countries in Africa. Methods: This is a secondary analysis of data from the African Neonatal Sepsis (AFRINEST) trial, conducted in the Democratic Republic of the Congo (DRC), Kenya, and Nigeria between 15 March 2012 and 15 July 2013. We recorded baseline characteristics, the incidence of PSBI (as defined by the World Health Organization), and the incidence of local infections among infants from 0-59 days after birth. We report descriptive statistics. Results: The incidence of PSBI among 0-59-day-old infants across all three countries was 11.2% (95% confidence interval (CI) = 11.0-11.4). The DRC had the highest incidence of PSBI (19.0%; 95% CI = 18.2-19.8). Likewise, PSBI rates were higher in low birth weight infants (24.5%; 95% CI = 23.1-26.0) and infants born to mothers aged <20 years (14.1%; 95% CI = 13.4-14.8). The incidence of PSBI was higher among infants delivered at home (11.7%; 95% CI = 11.4-12.0). Conclusions: The high burden of PSBI among young infants in DRC, Kenya, and Nigeria demonstrates the importance of addressing PSBI in improving child survival in sub-Saharan Africa to reach the Sustainable Development Goals (SDGs). These data can support government authorities, policymakers, programme implementers, non-governmental organisations, and international partners in reducing preventable under-five deaths. Registration: Australian New Zealand Clinical Trials Registry: ACTRN12610000286044.

Neurodevelopment of Children Whose Mothers Were Randomized to Low-Dose Aspirin During Pregnancy.

OBJECTIVE: Because low-dose aspirin is now commonly prescribed in pregnancy, we sought to assess the association between early antenatal exposure and child neurodevelopment. METHODS: We performed a noninferiority, masked, neurodevelopmental follow-up study of children between age 33 and 39 months whose mothers had been randomized to daily low-dose aspirin (81 mg) or placebo between 6 0/7 and 13 6/7 weeks of gestation through 37 weeks. Neurodevelopment was assessed with the Bayley-III (Bayley Scales of Infant and Toddler Development, 3rd Edition) and the ASQ-3 (Ages and Stages Questionnaire, 3rd Edition). The primary outcome was the Bayley-III cognitive composite score with a difference within 4 points demonstrating noninferiority. RESULTS: A total of 640 children (329 in the low-dose aspirin group, 311 in the placebo group) were evaluated between September 2021 and June 2022. The Bayley-III cognitive composite score was noninferior between the two groups (-1, adjusted mean -0.8, 95% CI, -2.2 to 0.60). Significant differences were not seen in the language composite score (difference 0.7, 95% CI, -0.8 to 2.1) or the motor composite score (difference -0.6, 95% CI, -2.5 to 1.2). The proportion of children who had any component of the Bayley-III score lower than 70 did not differ between the two groups. Similarly, the communication, gross motor, fine motor, problem-solving, and personal-social components of the ASQ-3 did not differ between groups. Maternal characteristics, delivery outcomes, breastfeeding rates, breastfeeding duration, and home environment as measured by the Family Care Indicators were similar. CONCLUSION: Antenatal low-dose aspirin exposure was not associated with altered neurodevelopmental outcomes at age 3 years. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT04888377.

Neonatal Respiratory Support Utilization in Low- and Middle-Income Countries: A Registry-Based Observational Study.

BACKGROUND: Newborns with hypoxemia often require life-saving respiratory support. In low-resource settings, it is unknown if respiratory support is delivered more frequently to term infants or preterm infants. We hypothesized that in a registry-based birth cohort in 105 geographic areas in seven low- and middle-income countries, more term newborns received respiratory support than preterm newborns. METHODS: This is a hypothesis-driven observational study based on prospectively collected data from the Maternal and Newborn Health Registry of the NICHD Global Network for Women's and Children's Health Research. Eligible infants enrolled in the registry were live-born between 22 and 44 weeks gestation with a birth weight ≥400 g and born from January 1, 2015, to December 31, 2018. Frequency data were obtained to report the number of term and preterm infants who received treatment with oxygen only, CPAP, or mechanical ventilation. Test for trends over time were conducted using robust Poisson regression. RESULTS: 177,728 (86.3%) infants included in this study were term, and 28,249 (13.7%) were preterm. A larger number of term infants (n = 5,108) received respiratory support compared to preterm infants (n = 3,287). Receipt of each mode of respiratory support was more frequent in term infants. The proportion of preterm infants who received respiratory support (11.6%) was higher than the proportion of term infants receiving respiratory support (2.9%, p < 0.001). The rate of provision of respiratory support varied between sites. CONCLUSIONS: Respiratory support was more frequently used in term infants expected to be at low risk for respiratory disorders compared to preterm infants.

Maternal age extremes and adverse pregnancy outcomes in low-resourced settings.

Introduction: Adolescent (<20 years) and advanced maternal age (>35 years) pregnancies carry adverse risks and warrant a critical review in low- and middle-income countries where the burden of adverse pregnancy outcomes is highest. Objective: To describe the prevalence and adverse pregnancy (maternal, perinatal, and neonatal) outcomes associated with extremes of maternal age across six countries. Patients and methods: We performed a historical cohort analysis on prospectively collected data from a population-based cohort study conducted in the Democratic Republic of Congo, Guatemala, India, Kenya, Pakistan, and Zambia between 2010 and 2020. We included pregnant women and their neonates. We describe the prevalence and adverse pregnancy outcomes associated with pregnancies in these maternal age groups (<20, 20-24, 25-29, 30-35, and >35 years). Relative risks and 95% confidence intervals of each adverse pregnancy outcome comparing each maternal age group to the reference group of 20-24 years were obtained by fitting a Poisson model adjusting for site, maternal age, parity, multiple gestations, maternal education, antenatal care, and delivery location. Analysis by region was also performed. Results: We analyzed 602,884 deliveries; 13% (78,584) were adolescents, and 5% (28,677) were advanced maternal age (AMA). The overall maternal mortality ratio (MMR) was 147 deaths per 100,000 live births and increased with advancing maternal age: 83 in the adolescent and 298 in the AMA group. The AMA groups had the highest MMR in all regions. Adolescent pregnancy was associated with an adjusted relative risk (aRR) of 1.07 (1.02-1.11) for perinatal mortality and 1.13 (1.06-1.19) for neonatal mortality. In contrast, AMA was associated with an aRR of 2.55 (1.81 to 3.59) for maternal mortality, 1.58 (1.49-1.67) for perinatal mortality, and 1.30 (1.20-1.41) for neonatal mortality, compared to pregnancy in women 20-24 years. This pattern was overall similar in all regions, even in the <18 and 18-19 age groups. Conclusion: The maternal mortality ratio in the LMICs assessed is high and increased with advancing maternal age groups. While less prevalent, AMA was associated with a higher risk of adverse maternal mortality and, like adolescence, was associated with adverse perinatal mortality with little regional variation.

A novel duplex qualitative real-time PCR assay for the detection and differentiation of Plasmodium ovale curtisi and Plasmodium ovale wallikeri malaria.

Background: P. ovale spp. infections are endemic across multiple African countries and are caused by two distinct non-recombining species, P. ovale curtisi (Poc) and P. ovale wallikeri (Pow). These species are thought to differ in clinical symptomatology and latency, but existing diagnostic assays have limited ability to detect and distinguish them. In this study, we developed a new duplex assay for the detection and differentiation of Poc and Pow that can be used to improve our understanding of these parasites. Methods: Repetitive sequence motifs were identified in available Poc and Pow genomes and used for assay development and validation. We evaluated the analytical sensitivity and specificity of the best-performing assay using a panel of samples from Tanzania and the Democratic Republic of the Congo (DRC), then validated its performance using 55 P. ovale spp. samples and 40 non-ovale Plasmodium samples from the DRC. Poc and Pow prevalence among symptomatic individuals sampled across three provinces of the DRC were estimated. Results: The best-performing Poc and Pow targets had 9 and 8 copies within the reference genomes, respectively. Our duplex assay had 100% specificity and 95% confidence lower limits of detection of 4.2 and 41.2 parasite genome equivalents/µl for Poc and Pow, respectively. Species was determined in 80% of all P. ovale spp.-positive field samples and 100% of those with >10 parasites/µl. Most P. ovale spp. field samples from the DRC were found to be Poc infections. Conclusions: We identified promising multi-copy targets for molecular detection and differentiation of Poc and Pow and used them to develop a new duplex real-time PCR assay that performed well when applied to diverse field samples. Though low-density Pow infections are not reliably detected, the assay is highly specific and can be used for high-throughput studies of P. ovale spp. epidemiology among symptomatic cases in malaria-endemic countries like the DRC.

Epidemiology of Plasmodium malariae and Plasmodium ovale spp. in a highly malaria-endemic country: a longitudinal cohort study in Kinshasa Province, Democratic Republic of Congo.

Background: Increasing reports suggest that non-falciparum species are an underappreciated cause of malaria in sub-Saharan Africa, but their epidemiology is not well-defined. This is particularly true in regions of high P. falciparum endemicity such as the Democratic Republic of Congo (DRC), where 12% of the world's malaria cases and 13% of deaths occur. Methods and Findings: The cumulative incidence and prevalence of P. malariae and P. ovale spp. infection detected by real-time PCR were estimated among children and adults within a longitudinal study conducted in seven rural, peri-urban, and urban sites from 2015-2017 in Kinshasa Province, DRC. Participants were sampled at biannual household survey visits (asymptomatic) and during routine health facility visits (symptomatic). Participant-level characteristics associated with non-falciparum infections were estimated for single- and mixed-species infections. Among 9,089 samples collected from 1,565 participants over a 3-year period, the incidence of P. malariae and P. ovale spp. infection was 11% (95% CI: 9%-12%) and 7% (95% CI: 5%-8%) by one year, respectively, compared to a 67% (95% CI: 64%-70%) one-year cumulative incidence of P. falciparum infection. Incidence continued to rise in the second year of follow-up, reaching 26% and 15% in school-age children (5-14yo) for P. malariae and P. ovale spp., respectively. Prevalence of P. malariae, P. ovale spp., and P. falciparum infections during household visits were 3% (95% CI: 3%-4%), 1% (95% CI: 1%-2%), and 35% (95% CI: 33%-36%), respectively. Non-falciparum malaria was more prevalent in rural and peri-urban vs. urban sites, in school-age children, and among those with P. falciparum co-infection. A crude association was detected between P. malariae and any anemia in the symptomatic clinic population, although this association did not hold when stratified by anemia severity. No crude associations were detected between non-falciparum infection and fever prevalence. Conclusions: P. falciparum remains the primary driver of malaria morbidity and mortality in the DRC. However, non-falciparum species also pose an infection risk across sites of varying urbanicity and malaria endemicity within Kinshasa, DRC, particularly among children under 15 years of age. As P. falciparum interventions gain traction in high-burden settings like the DRC, continued surveillance and improved understanding of non-falciparum infections are warranted.

Assessing caregivers' perceptions of treatment-seeking for suspected severe malaria in the Democratic Republic of the Congo.

BACKGROUND: Malaria remains a major public health issue in the Democratic Republic of the Congo (DRC), accounting for 44% deaths among outpatient visits in children < 5 years of age, and 22% of facility deaths. Understanding determinants of caregivers' treatment-seeking patterns and decision-making is crucial in reducing the malaria burden. METHODS: In the frame of the Community Access to Rectal Artesunate for Malaria (CARAMAL) project, cross-sectional household surveys that randomly sampled villages and households were carried-out in three rural DRC health zones prior to the rollout of pre-referral Rectal Artesunate (RAS) and then 9 and 19 months after RAS rollout (post-RAS). Data were captured electronically through face-to-face interviews with the main caregivers of children < 5 years. Capillary blood samples of the children were tested for malaria and anaemia. The main study outcome was whether caregiver "sought treatment outside home" when the child had fever. Multilevel mixed effects logistic regression models using village as random effect and health zone as a fixed effect was performed to assess treatment-seeking predictors. RESULTS: 2439 household interviews were completed (pre-RAS 888 and post-RAS 1551), including 316 and 653 treatment-seeking interviews. Overall, 3499 children < 5 years were tested for malaria and anaemia (pre-RAS 1,315 and post-RAS 2184). Caregiver's recognition of severe malaria signs was poor, while knowledge of symptoms of uncomplicated malaria seemed high. Despite this, danger signs significantly increased the odds of seeking treatment (aOR = 2.12, 95%CI 1.03-4.38), the same was found for the "least poor" quintile (aOR = 3.01, 95%CI 1.03-8.82), as well as residents of Kingandu (aOR = 2.78, 95%CI 1.01-7.65). "Doing something at home" against fever negatively affected treatment-seeking in both study phases. RAS acceptance was high, at almost 100%. Malaria prevalence was higher post-RAS (45.2%) compared to pre-RAS (34.4%), p = 0.003, but anaemia, although high (≥ 75%), was similar in both study phases (p = 0.92). CONCLUSION: In remote communities with high malaria prevalence in the DRC, malaria remains a major problem. Improving the recognition of danger signs of severe disease and introducing pre-referral RAS may improve treatment-seeking and contribute to reducing malaria-related mortality among children-if quality of care can be guaranteed.

Epidemiology of Plasmodium malariae and Plasmodium ovale spp. in Kinshasa Province, Democratic Republic of Congo.

Reports suggest non-falciparum species are an underappreciated cause of malaria in sub-Saharan Africa but their epidemiology is ill-defined, particularly in highly malaria-endemic regions. We estimated incidence and prevalence of PCR-confirmed non-falciparum and Plasmodium falciparum malaria infections within a longitudinal study conducted in Kinshasa, Democratic Republic of Congo (DRC) between 2015-2017. Children and adults were sampled at biannual household surveys and routine clinic visits. Among 9,089 samples from 1,565 participants, incidences of P. malariae, P. ovale spp., and P. falciparum infections by 1-year were 7.8% (95% CI: 6.4%-9.1%), 4.8% (95% CI: 3.7%-5.9%) and 57.5% (95% CI: 54.4%-60.5%), respectively. Non-falciparum prevalences were higher in school-age children, rural and peri-urban sites, and P. falciparum co-infections. P. falciparum remains the primary driver of malaria in the DRC, though non-falciparum species also pose an infection risk. As P. falciparum interventions gain traction in high-burden settings, continued surveillance and improved understanding of non-falciparum infections are warranted.

Building a predictive model of low birth weight in low- and middle-income countries: a prospective cohort study.

BACKGROUND: Low birth weight (LBW, < 2500 g) infants are at significant risk for death and disability. Improving outcomes for LBW infants requires access to advanced neonatal care, which is a limited resource in low- and middle-income countries (LMICs). Predictive modeling might be useful in LMICs to identify mothers at high-risk of delivering a LBW infant to facilitate referral to centers capable of treating these infants. METHODS: We developed predictive models for LBW using the NICHD Global Network for Women's and Children's Health Research Maternal and Newborn Health Registry. This registry enrolled pregnant women from research sites in the Democratic Republic of the Congo, Zambia, Kenya, Guatemala, India (2 sites: Belagavi, Nagpur), Pakistan, and Bangladesh between January 2017 - December 2020. We tested five predictive models: decision tree, random forest, logistic regression, K-nearest neighbor and support vector machine. RESULTS: We report a rate of LBW of 13.8% among the eight Global Network sites from 2017-2020, with a range of 3.8% (Kenya) and approximately 20% (in each Asian site). Of the five models tested, the logistic regression model performed best with an area under the curve of 0.72, an accuracy of 61% and a recall of 72%. All of the top performing models identified clinical site, maternal weight, hypertensive disorders, severe antepartum hemorrhage and antenatal care as key variables in predicting LBW. CONCLUSIONS: Predictive modeling can identify women at high risk for delivering a LBW infant with good sensitivity using clinical variables available prior to delivery in LMICs. Such modeling is the first step in the development of a clinical decision support tool to assist providers in decision-making regarding referral of these women prior to delivery. Consistent referral of women at high-risk for delivering a LBW infant could have extensive public health consequences in LMICs by directing limited resources for advanced neonatal care to the infants at highest risk.

Malaria in Pregnancy: Key Points for the Neonatologist.

In malaria-endemic regions, infection with the malaria parasite Plasmodium during pregnancy has been identified as a key modifiable factor in preterm birth, the delivery of low-birthweight infants, and stillbirth. Compared with their nonpregnant peers, pregnant persons are at higher risk for malaria infection. Malaria infection can occur at any time during pregnancy, with negative effects for the pregnant person and the fetus, depending on the trimester in which the infection is contracted. Pregnant patients who are younger, in their first or second pregnancy, and those coinfected with human immunodeficiency virus are at increased risk for malaria. Common infection prevention measures during pregnancy include the use of insecticide-treated bed nets and the use of intermittent preventive treatment with monthly doses of antimalarials, beginning in the second trimester in pregnant patients in endemic areas. In all trimesters, artemisinin-combination therapies are the first-line treatment for uncomplicated falciparum malaria, similar to treatment in nonpregnant adults. The World Health Organization recently revised its recommendations, now listing the specific medication artemether-lumefantrine as first-line treatment for uncomplicated malaria in the first trimester. While strong prevention and detection methods exist, use of these techniques remains below global targets. Ongoing work on approaches to treatment and prevention of malaria during pregnancy remains at the forefront of global maternal child health research.

Trends over time in the knowledge, attitude and practices of pregnant women related to COVID-19: A cross-sectional survey from seven low- and middle-income countries.

OBJECTIVE: To understand trends in the knowledge, attitudes and practices (KAP) of pregnant women related to COVID-19 in seven low- and middle-income countries. DESIGN: Multi-country population-based prospective observational study. SETTING: Study sites in Bangladesh, the Demographic Republic of Congo (DRC), Guatemala, India (two sites), Kenya, Pakistan and Zambia. POPULATION: Pregnant women in the Global Network's Maternal and Neonatal Health Registry (MNHR). METHODS: Pregnant women enrolled in the MNHR were interviewed to assess their KAP related to COVID-19 from September 2020 through July 2022 across all study sites. MAIN OUTCOME MEASURES: Trends of COVID-19 KAP were assessed using the Cochran-Armitage test for trend. RESULTS: A total of 52 297 women participated in this study. There were wide inter-country differences in COVID-19-related knowledge. The level of knowledge of women in the DRC was much lower than that of women in the other sites. The ability to name COVID-19 symptoms increased over time in the African sites, whereas no such change was observed in Bangladesh, Belagavi and Guatemala. All sites observed decreasing trends over time in women avoiding antenatal care visits. CONCLUSIONS: The knowledge and attitudes of pregnant women related to COVID-19 varied substantially among the Global Network sites over a period of 2 years; however, there was very little change in knowledge related to COVID-19 over time across these sites. The major change observed was that fewer women reported avoiding medical care because of COVID-19 across all sites over time.

The impact of risk factors on aspirin's efficacy for the prevention of preterm birth.

BACKGROUND: The Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas trial was a landmark study that demonstrated a reduction in preterm birth and hypertensive disorders of pregnancy in nulliparous women who received low-dose aspirin. All women in the study had at least 1 moderate-risk factor for preeclampsia (nulliparity). Unlike current US Preventative Service Task Force guidelines, which recommend low-dose aspirin for ≥2 moderate-risk factors, women in this study were randomized to receive low-dose aspirin regardless of the presence or absence of an additional risk factor. OBJECTIVE: This study aimed to compare how low-dose aspirin differentially benefits nulliparous women with and without additional preeclampsia risk factors for the prevention of preterm birth and hypertensive disorders of pregnancy. STUDY DESIGN: This was a non-prespecified secondary analysis of the Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas trial that randomized nulliparous women with singleton pregnancies from 6 low-middle-income countries to receive low-dose aspirin or placebo. Our primary exposure was having an additional preeclampsia risk factor beyond nulliparity. Our primary outcome was preterm birth before 37 weeks of gestation, and our secondary outcomes included preterm birth before 34 weeks of gestation, preterm birth before 28 weeks of gestation, hypertensive disorders of pregnancy, and perinatal mortality. RESULTS: Among 11,558 nulliparous women who met the inclusion criteria, 66.8% had no additional risk factors. Low-dose aspirin similarly reduced the risk of preterm birth at <37 weeks of gestation in women with and without additional risk factors (relative risk: 0.75 vs 0.85; P=.35). Additionally for our secondary outcomes, low-dose aspirin similarly reduced the risk of preterm birth at <28 weeks of gestation, hypertensive disorders of pregnancy, and perinatal mortality in women with and without additional risk factors. The reduction of preterm birth at <34 weeks of gestation with low-dose aspirin was significantly greater in women without additional risk factors than those with an additional risk factor (relative risk: 0.69 vs 1.04; P=.04). CONCLUSION: Low-dose aspirin's ability to prevent preterm birth, hypertensive disorders of pregnancy, and perinatal mortality was similar in nulliparous women with and without additional risk factors. Professional societies should consider recommending low-dose aspirin to all nulliparous women.

COVID-19 symptoms and antibody positivity among unvaccinated pregnant women: An observational study in seven countries from the Global Network.

OBJECTIVE: To determine the relation of COVID-19 symptoms to COVID-19 antibody positivity among unvaccinated pregnant women in low- and middle-income countries (LMIC). DESIGN: COVID-19 infection status measured by antibody positivity at delivery was compared with the symptoms of COVID-19 in the current pregnancy in a prospective, observational cohort study in seven LMICs. SETTING: The study was conducted among women in the Global Network for Women's and Children's Health's Maternal and Newborn Health Registry (MNHR), a prospective, population-based study in Kenya, Zambia, the Democratic Republic of the Congo (DRC), Bangladesh, Pakistan, India (Belagavi and Nagpur sites) and Guatemala. POPULATION: Pregnant women enrolled in the ongoing pregnancy registry at study sites. METHODS: Data on COVID-19 symptoms during the current pregnancy were collected by trained staff between October 2020 and June 2022. COVID-19 antibody testing was performed on samples collected at delivery. The relation between COVID-19 antibody positivity and symptoms was assessed using generalised linear models with a binomial distribution adjusting for site and symptoms. MAIN OUTCOME MEASURES: COVID-19 antibody status and symptoms of COVID-19 among pregnant women. RESULTS: Among 19 218 non-vaccinated pregnant women who were evaluated, 14.1% of antibody-positive women had one or more symptoms compared with 13.4% in antibody-negative women. Overall, 85.3% of antibody-positive women reported no COVID-19 symptoms during the present pregnancy. Reported fever was significantly associated with antibody status (relative risk [RR] 1.10, 95% CI 1.03-11.18; P = 0.008). A multiple variable model adjusting for site and all eight symptoms during pregnancy showed similar results (RR 1.13, 95% CI 1.04-1.23; P = 0.012). None of the other symptoms was significantly related to antibody positivity. CONCLUSIONS: In a population-based cohort in LMICs, unvaccinated pregnant women who were antibody-positive had slightly more symptoms during their pregnancy and a small but significantly greater increase in fever. However, for prevalence studies, evaluating COVID-19-related symptoms does not appear to be useful in differentiating pregnant women who have had a COVID-19 infection.

Aspirin delays the onset of hypertensive disorders of pregnancy among nulliparous pregnant women: A secondary analysis of the ASPIRIN trial.

OBJECTIVE: To assess the impact of low-dose aspirin (LDA) starting in early pregnancy on delaying preterm hypertensive disorders of pregnancy. DESIGN: Non-prespecified secondary analysis of a randomised masked trial of LDA. SETTING: The study was conducted among women in the Global Network for Women's and Children's Health's Maternal and Newborn Health Registry (MNHR) clusters, a prospective, population-based study in Kenya, Zambia, the Democratic Republic of the Congo (DRC), Pakistan, India (two sites-Belagavi and Nagpur) and Guatemala. POPULATION: Nulliparous singleton pregnancies between 6+0 weeks and 13+6 weeks in six low-middle income countries (Democratic Republic of Congo, Guatemala, India, Kenya, Pakistan, Zambia) enrolled in the ASPIRIN Trial. METHODS: We compared the incidence of HDP at delivery at three gestational age periods (<28, <34 and <37 weeks) between women who were randomised to aspirin or placebo. Women were included if they were randomised and had an outcome at or beyond 20 weeks (Modified Intent to Treat). MAIN OUTCOME MEASURES: Our primary outcome was pregnancies with HDP associated with preterm delivery (HDP@delivery) before <28, <34 and <37 weeks. Secondary outcomes included small for gestational age (SGA) <10th percentile, <5th percentile, and perinatal mortality. RESULTS: Among the 11 976 pregnancies, LDA did not significantly lower HDP@delivery <28 weeks (relative risk [RR] 0.18, 95% confidence interval [CI] 0.02-1.52); however, it did lower HDP@delivery <34 weeks (RR 0.37, 95% CI 0.17-0.81) and HDP@delivery <37 weeks (RR 0.66, 95% CI 0.49-0.90). The overall rate of HDP did not differ between the two groups (RR 1.08, 95% CI 0.94-1.25). Among those pregnancies who had HDP, SGA <10th percentile was reduced (RR 0.81, 95% CI 0.67-0.99), though SGA <5th percentile was not (RR 0.84, 95% CI 0.64-1.09). Similarly, perinatal mortality among pregnancies with HDP occurred less frequently (RR 0.55, 95% CI 0.33-0.92) in those receiving LDA. Pregnancies randomised to LDA delivered later with HDP compared with those receiving placebo (median gestational age 38.5 weeks vs. 37.9 weeks; p = 0.022). CONCLUSIONS: In this secondary analysis of a study of low-risk nulliparous singleton pregnancies, early administration of LDA resulted in lower rates of preterm HDP and delivery before 34 and 37 weeks but not in the overall rate of HDP. These results suggest that LDA works in part by delaying HDP.

Impact of malaria diagnostic choice on monitoring of Plasmodium falciparum prevalence estimates in the Democratic Republic of the Congo and relevance to control programs in high-burden countries.

Malaria programs rely upon a variety of diagnostic assays, including rapid diagnostic tests (RDTs), microscopy, polymerase chain reaction (PCR), and bead-based immunoassays (BBA), to monitor malaria prevalence and support control and elimination efforts. Data comparing these assays are limited, especially from high-burden countries like the Democratic Republic of the Congo (DRC). Using cross-sectional and routine data, we compared diagnostic performance and Plasmodium falciparum prevalence estimates across health areas of varying transmission intensity to illustrate the relevance of assay performance to malaria control programs. Data and samples were collected between March-June 2018 during a cross-sectional household survey across three health areas with low, moderate, and high transmission intensities within Kinshasa Province, DRC. Samples from 1,431 participants were evaluated using RDT, microscopy, PCR, and BBA. P. falciparum parasite prevalence varied between diagnostic methods across all health areas, with the highest prevalence estimates observed in Bu (57.4-72.4% across assays), followed by Kimpoko (32.6-53.2%), and Voix du Peuple (3.1-8.4%). Using latent class analysis to compare these diagnostic methods against an "alloyed gold standard," the most sensitive diagnostic method was BBA in Bu (high prevalence) and Voix du Peuple (low prevalence), while PCR diagnosis was most sensitive in Kimpoko (moderate prevalence). RDTs were consistently the most specific diagnostic method in all health areas. Among 9.0 million people residing in Kinshasa Province in 2018, the estimated P. falciparum prevalence by microscopy, PCR, and BBA were nearly double that of RDT. Comparison of malaria RDT, microscopy, PCR, and BBA results confirmed differences in sensitivity and specificity that varied by endemicity, with PCR and BBA performing best for detecting any P. falciparum infection. Prevalence estimates varied widely depending on assay type for parasite detection. Inherent differences in assay performance should be carefully considered when using community survey and surveillance data to guide policy decisions.

Association between domesticated animal ownership and Plasmodium falciparum parasite prevalence in the Democratic Republic of the Congo: a national cross-sectional study.

BACKGROUND: Domesticated animal ownership is an understudied aspect of the human environment that influences mosquito biting behaviour and malaria transmission, and is a key part of national economies and livelihoods in malaria-endemic regions. In this study, we aimed to understand differences in Plasmodium falciparum prevalence by ownership status of common domesticated animals in DR Congo, where 12% of the world's malaria cases occur and anthropophilic Anopheles gambiae vectors predominate. METHODS: In this cross-sectional study, we used survey data from individuals aged 15-59 years in the most recent (2013-14) DR Congo Demographic and Health Survey and previously performed Plasmodium quantitative real-time PCR (qPCR) to estimate P falciparum prevalence differences by household ownership of cattle; chickens; donkeys, horses, or mules; ducks; goats; sheep; and pigs. We used directed acyclic graphs to consider confounding by age, gender, wealth, modern housing, treated bednet use, agricultural land ownership, province, and rural location. FINDINGS: Of 17 701 participants who had qPCR results and covariate data, 8917 (50·4%) of whom owned a domesticated animal, we observed large differences in malaria prevalence across types of animals owned in both crude and adjusted models. Household chicken ownership was associated with 3·9 (95% CI 0·6 to 7·1) more P falciparum infections per 100 people, whereas cattle ownership was associated with 9·6 (-15·8 to -3·5) fewer P falciparum infections per 100 people, even after accounting for bednet use, wealth, and housing structure. INTERPRETATION: Our finding of a protective association conferred by cattle ownership suggests that zooprophylaxis interventions might have a role in DR Congo, possibly by drawing An gambiae feeding away from humans. Studies of animal husbandry practices and associated mosquito behaviours could reveal opportunities for new malaria interventions. FUNDING: The National Institutes of Health and the Bill & Melinda Gates Foundation. TRANSLATIONS: For the French and Lingala translations of the abstract see Supplementary Materials section.

Plasmodium falciparum with pfhrp2/3 Deletion Not Detected in a 2018-2021 Malaria Longitudinal Cohort Study in Kinshasa Province, Democratic Republic of the Congo.

Histidine-rich protein 2- (HRP2-) based rapid diagnostic tests (RDTs) are widely used to detect Plasmodium falciparum in sub-Saharan Africa. Reports of parasites with pfhrp2 and/or pfhrp3 (pfhrp2/3) gene deletions in Africa raise concerns about the long-term viability of HRP2-based RDTs. We evaluated changes in pfhrp2/3 deletion prevalence over time using a 2018-2021 longitudinal study of 1,635 enrolled individuals in Kinshasa Province, Democratic Republic of the Congo (DRC). Samples collected during biannual household visits with ≥ 100 parasites/µL by quantitative real-time polymerase chain reaction were genotyped using a multiplex real-time PCR assay. Among 2,726 P. falciparum PCR-positive samples collected from 993 participants during the study period, 1,267 (46.5%) were genotyped. No pfhrp2/3 deletions or mixed pfhrp2/3-intact and -deleted infections were identified in our study. Pfhrp2/3-deleted parasites were not detected in Kinshasa Province; ongoing use of HRP2-based RDTs is appropriate.