Pharmacokinetics of piperaquine and its association with intermittent malaria preventive therapy outcomes during pregnancy.

BACKGROUND: Dihydroartemisinin-piperaquine (DHP) recently showed superior effectiveness over sulfadoxine-pyrimethamine for malaria intermittent preventive treatment in pregnancy (IPTp). We investigated day 7 piperaquine pharmacokinetics and its therapeutic efficacy in preventing malaria during pregnancy. METHODS: Malaria-free (mRDT) pregnant women (n = 400) who received monthly IPTp-DHP were enrolled and followed till delivery. Day 7 Plasma piperaquine concentrations were determined after each IPTp dose using UPLC/MS/MS. IPTp outcomes (symptomatic malaria and parasitemia during pregnancy, placental malaria, and maternal malaria at delivery) were monitored. Linear mixed model and Cox regression were used to assess predictors of day 7 piperaquine concentration and treatment outcome, respectively. RESULTS: The incidences of symptomatic malaria and parasitemia during pregnancy per 100 person-year at risk were 2 and 33, respectively. The prevalence of histopathologically confirmed placental malaria and maternal malaria at delivery were 3% and 9.8%, respectively. Repeated monthly IPTp-DHP resulted in significantly increased day 7 plasma piperaquine concentration (p < 0.001). Following the 1st, 2nd, and 3rd monthly IPTp-DHP doses, the proportions of women with day 7 piperaquine concentration below the therapeutic threshold (< 30 ng/mL) were 6.1%, 4.1% and 3.6%, respectively. Factors such as maternal age, body weight and trimester were not significant predictors of day 7 piperaquine concentration. However, having a low day 7 piperaquine plasma concentration (< 30 ng/mL) was significantly associated with a higher risk of parasitemia during pregnancy (p = 0.004). CONCLUSION: Lower day 7 piperaquine plasma concentration is a risk factor for parasitemia during pregnancy. Single plasma sampling at day 7 can be used to monitor piperaquine effectiveness during IPTp-DHP. TRIAL REGISTRATION: Registered 09/12/2016, PACTR201612001901313.

Asymptomatic malaria in pregnancy and associated risk factors in Majang Zone, Gambella Region, Southwest Ethiopia: a hard-to-reach malaria hotspot.

BACKGROUND: Asymptomatic malaria in pregnancy (AMiP) is a daunting public health problem with multifaceted adverse outcomes for mothers, fetuses, newborns and beyond. This study aimed to assess the prevalence and risk factors of AMiP and anaemia in Majang Zone, Gambella, Southwest Ethiopia. METHODS: A facility-based cross-sectional study was conducted among 425 pregnant women attending the antenatal care (ANC) clinics of five health facilities in the Majang Zone from November 2022 to February 2023. Sociodemographic, obstetric, and anti-malarial intervention data were collected using an interviewer-administered questionnaire. A capillary blood specimen was collected to diagnose malaria and anaemia as well as determine the blood group. Malaria was diagnosed by rapid diagnostic test (RDT), microscopy, and quantitative polymerase chain reaction (qPCR). Statistical analyses were done by Statistical Package for Social Science (SPSS) version 26.0. The association between dependent and independent variables was assessed by multivariable binary logistic regression, considering P < 0.05 statistically significant. The magnitude of associations was quantified with the adjusted odds ratio (AOR) along with the corresponding 95% confidence interval (CI). RESULTS: The overall prevalence of AMiP was 15.3% (95% CI 12.1, 18.9). It was 11.3% (95% CI 8.4, 14.7) by RDT, 11.8% (95% CI 8.9, 15.2) by microscopy and 17.6% (95% CI 11.7, 24.9) by qPCR. Plasmodium falciparum, moderate parasitaemia and submicroscopic infection accounted for 55.4% of the AMiP prevalence, 50.8% of the parasite density, and 41.6% of the qPCR-positive AMiP, respectively. Nearly 32.3% of pregnant women with AMiP carried gametocytes. Risk factors of AMiP were: not utilizing insecticide-treated net (ITN) within the previous week (AOR: 9.43 95% CI 1.57, 56.62), having a history of malaria within the previous year (AOR: 2.26 95% CI 1.16, 4.42), lack of indoor residual spraying (IRS) within the previous year (AOR: 3.00 95% CI 1.50, 6.00), and ANC contact below two rounds (AOR: 4.28 95% CI 2.06, 8.87). The prevalence of anaemia was 27.7% (95% CI 23.6, 32.1), and it was higher among AMiP-positives (56.9%) than the negatives (22.5%) (P: 000). CONCLUSION: The prevalence of AMiP and anaemia was high, and remained as a critical public health problem in the study area. Focus on the identified risk factors and introduction of more sensitive diagnostic tools should be considered to mitigate AMiP in the study area.

Sub-microscopic Plasmodium falciparum infections and multiple drug resistant single nucleotide polymorphic alleles in pregnant women from southwestern Nigeria.

OBJECTIVES: The study evaluated sub-microscopic malaria infections in pregnancy using two malaria Rapid Diagnostic Tests (mRDTs), microscopy and RT-PCR and characterized Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and Plasmodium falciparum dihydropteroate synthase (Pfdhps) drug resistant markers in positive samples. METHODS: This was a cross sectional survey of 121 pregnant women. Participants were finger pricked, blood drops were collected for rapid diagnosis with P. falciparum histidine-rich protein 11 rapid diagnostic test kit and the ultra-sensitive Alere Pf malaria RDT, Blood smears for microscopy and dried blood spots on Whatman filter paper for molecular analysis were made. Real time PCR targeting the var acidic terminal sequence (varATS) gene of P. falciparum was carried out on a CFX 96 real time system thermocycler (BioRad) in discriminating malaria infections. For each run, laboratory strain of P. falciparum 3D7 and nuclease free water were used as positive and negative controls respectively. Additionally, High resolution melt analyses was employed for genotyping of the different drug resistance markers. RESULTS: Out of one hundred and twenty-one pregnant women sampled, the SD Bioline™ Malaria Ag P.f HRP2-based malaria rapid diagnostic test (mRDT) detected eight (0.06%) cases, the ultra-sensitive Alere™ malaria Ag P.f rapid diagnostic test mRDT had similar outcome in the same samples as detected by the HRP2-based mRDT. Microscopy and RT-PCR confirmed four out of the eight infections detected by both rapid diagnostic tests as true positive and RT-PCR further detected three false negative samples by the two mRDTs providing a sub-microscopic malaria prevalence of 3.3%. Single nucleotide polymorphism in Pfdhps gene associated with sulphadoxine resistance revealed the presence of S613 mutant genotypes in three of the seven positive isolates and isolates with mixed wild/mutant genotype at codon A613S. Furthermore, four mixed genotypes at the A581G codon were also recorded while the other Pfdhps codons (A436G, A437G and K540E) showed the presence of wild type alleles. In the Pfdhfr gene, there were mutations in 28.6%, 28.6%, and 85.7% at the I51, R59 and N108 codons respectively. Mixed wild and mutant type genotypes were also observed in 28.6% each of the N51I, and C59R codons. For the Pfcrt, two haplotypes CVMNK and CVIET were observed. The SVMNT was altogether absent. Triple mutant CVIET 1(14.3%) and triple mutant + wild genotype CVIET + CVMNK 1(14.3%) were observed. The Pfmdr1 haplotypes were single mutants YYND 1(14.3%); NFND 1(14.3%) and double mutants YFND 4(57.1%); YYDD 1(14.3%).

Trimethoprim-Sulfamethoxazole Plus Azithromycin to Prevent Malaria and Sexually Transmitted Infections in Pregnant Women With HIV (PREMISE): A Randomized, Double-Masked, Placebo-Controlled, Phase IIB Clinical Trial.

Background: This trial tested the effectiveness of a novel regimen to prevent malaria and sexually transmitted infections (STIs) among pregnant women with HIV in Cameroon. Our hypothesis was that the addition of azithromycin (AZ) to standard daily trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis would reduce malaria and STI infection rates at delivery. Methods: Pregnant women with HIV at gestational age <28 weeks were randomized to adjunctive monthly oral AZ 1 g daily or placebo for 3 days and both groups received daily standard oral TMP-SMX through delivery. Primary outcomes were (1) positive peripheral malaria infection by microscopy or polymerase chain reaction and (2) composite bacterial genital STI (Chlamydia trachomatis, Neisseria gonorrhoeae, or syphilis) at delivery. Relative risk and 95% confidence intervals were estimated using 2 × 2 tables with significance as P < .05. Results: Pregnant women with HIV (n = 308) were enrolled between March 2018 and August 2020: 155 women were randomized to TMP-SMX-AZ and 153 women to TMP-SMX-placebo. Groups were similar at baseline and loss to follow up was 3.2%. There was no difference in the proportion with malaria (16.3% in TMP-SMX-AZ vs 13.2% in TMP-SMX; relative risk, 1.24 [95% confidence interval, .71-2.16]) or STI at delivery (4.2% in TMP-SMX-AZ vs 5.8% in TMP-SMX; relative risk, 0.72 [95% confidence interval, .26-2.03]). Adverse birth outcomes were not significantly different, albeit lower in the TMP-SMX-AZ arm (preterm delivery 6.7% vs 10.7% [P = .3]; low birthweight 3.4% vs 5.4% [P = .6]). Conclusions: The addition of monthly azithromycin to daily TMP-SMX prophylaxis in pregnant women living with HIV in Cameroon did not reduce the risk of malaria or bacterial STI at delivery.

Monthly Sulfadoxine-Pyrimethamine During Pregnancy Prevents Febrile Respiratory Illnesses: A Secondary Analysis of a Malaria Chemoprevention Trial in Uganda.

Background: Trials evaluating antimalarials for intermittent preventive treatment in pregnancy (IPTp) have shown that dihydroartemisinin-piperaquine (DP) is a more efficacious antimalarial than sulfadoxine-pyrimethamine (SP); however, SP is associated with higher birthweight, suggesting that SP demonstrates "nonmalarial" effects. Chemoprevention of nonmalarial febrile illnesses (NMFIs) was explored as a possible mechanism. Methods: In this secondary analysis, we leveraged data from 654 pregnant Ugandan women without HIV infection who participated in a randomized controlled trial comparing monthly IPTp-SP with IPTp-DP. Women were enrolled between 12 and 20 gestational weeks and followed through delivery. NMFIs were measured by active and passive surveillance and defined by the absence of malaria parasitemia. We quantified associations among IPTp regimens, incident NMFIs, antibiotic prescriptions, and birthweight. Results: Mean "birthweight for gestational age" Z scores were 0.189 points (95% CI, .045-.333) higher in women randomized to IPTp-SP vs IPTp-DP. Women randomized to IPTp-SP had fewer incident NMFIs (incidence rate ratio, 0.74; 95% CI, .58-.95), mainly respiratory NMFIs (incidence rate ratio, 0.69; 95% CI, .48-1.00), vs IPTp-DP. Counterintuitively, respiratory NMFI incidence was positively correlated with birthweight in multigravidae. In total 75% of respiratory NMFIs were treated with antibiotics. Although overall antibiotic prescriptions were similar between arms, for each antibiotic prescribed, "birthweight for gestational age" Z scores increased by 0.038 points (95% CI, .001-.074). Conclusions: Monthly IPTp-SP was associated with reduced respiratory NMFI incidence, revealing a potential nonmalarial mechanism of SP and supporting current World Health Organization recommendations for IPTp-SP, even in areas with high-grade SP resistance. While maternal respiratory NMFIs are known risk factors of lower birthweight, most women in our study were presumptively treated with antibiotics, masking the potential benefit of SP on birthweight mediated through preventing respiratory NMFIs.

Experiences of young mothers with the uptake of Sulfadoxine-Pyrimethamine for intermittent preventive treatment of malaria in pregnancy: a cross-sectional study in the Lake endemic region, Kenya.

Background: A substantial proportion of the world population is affected by malaria with 241 million malaria cases reported globally. Intermittent Preventive Treatment in pregnancy (IPTp) with Sulfadoxine-Pyrimethamine (SP) is an effective chemotherapy but its utilisation has not been optimised. Few studies focus on young mothers and their experiences regarding the optimal uptake of IPTp-SP. Methods: The study design was cross-sectional with data derived from six focus group discussions with mothers aged 15-24 years who had a pregnancy and gave birth to a live baby within the last two years in Kisumu and Migori counties, Kenya. Inductive analysis was used to identify themes and patterns. Results: Young mothers were motivated to take IPTp-SP during pregnancy if they had prior knowledge about SP and its associated benefits and if they were knowledgeable about the consequences of malaria infection during pregnancy. Perceived side effects of SP, lack of awareness of SP as a malaria prevention therapy, lack of knowledge on the benefits of SP, dosage and frequency of uptake, poor communication by health providers towards young mothers, and inconsistent supply of SP at health facilities inhibited young mothers from attaining the recommended 3+ doses of IPTp-SP. Conclusions: There is a need for health literacy programmes that focus on increasing knowledge of IPTp-SP dosage, timing and benefits for both the young pregnant mother and her foetus. Community engagement through dialogue with mentor mothers and male partners will be an important complementary approach in establishing a support system for young women for positive health outcomes including attaining the recommended 3+ doses of IPTp-SP.

First malaria in pregnancy followed in Philippine real-world setting: proof-of-concept of probabilistic record linkage between disease surveillance and hospital administrative data.

BACKGROUND: Although the Philippines targets malaria elimination by 2030, it remains to be a disease that causes considerable morbidity in provinces that report malaria. Pregnant women residing in endemic areas are a vulnerable population, because in addition to the risk of developing severe malaria, their pregnancy is not followed through, and the outcome of their pregnancy is unknown. This study determined the utility of real-world data integrated with disease surveillance data set as real-world evidence of pregnancy and delivery outcomes in areas endemic for malaria in the Philippines. METHODS: For the period of 2015 to 2019, electronic data sets of malaria surveillance data and Ospital ng Palawan hospital admission log of pregnant women residing in the four selected barangays of Rizal, Palawan were merged using probabilistic linkage. The source data for record linkage were first and last names, birth date, and address as the mutual variable. The data used for characteristics of the pregnant women from the hospital data set were admission date, discharge date, admitting and final diagnosis and body weight on admission. From the malaria surveillance data these were date of consultation, and malaria parasite species. The Levenshtein distance formula was used for a fuzzy string-matching algorithm. Chi-square test, and Mann-Whitney U test were used to compare the means of the two data sets. RESULTS: The prevalence of pregnant women admitted to the tertiary referral hospital, Ospital ng Palawan, was estimated to be 8.34/100 overall, and 11.64/100 from the four study barangays; that of malaria during pregnancy patients was 3.45/100 and 2.64/100, respectively. There was only one true-positive matched case from 238 women from the hospital and 54 women from the surveillance data sets. The overall Levenshstein score was 97.7; for non-matched cases, the mean overall score was 36.6 (35.6-37.7). The matched case was a minor who was hospitalized for severe malaria. The outcome of her pregnancy was detected from neither data set but from village-based records. CONCLUSIONS: This proof-of-concept study demonstrated that probabilistic record linkage could match real-world data in the Philippines with further validation required. The study underscored the need for more integrated and comprehensive database to monitor disease intervention impact on pregnancy and its outcome in the Philippines.

Impact of the COVID-19 pandemic on malaria in pregnancy indicators in Northern Uganda: a joinpoint regression analysis.

BACKGROUND: Pregnancy is both a risk factor for P. falciparum infection and development of severe malaria. In low- and middle-income countries, the COVID-19 pandemic severely impacted health systems, including utilization of maternal services. This study aimed to assess trends in delivering malaria in pregnancy-related health-care services before and during COVID-19 in Northern Uganda. METHODS: An interrupted time-series study comparing pre-COVID-19 (January 2018 to April 2020) and COVID-19 (May to December 2021) periods, based on the date the first COVID case was detected. The study involved 30 health facilities in Northern Uganda with 22,650 estimated pregnancies per year, 14% of which took place in hospital. Monthly data were sourced from District routinely collected indicators. Trends were analyzed by joinpoint regression models. RESULTS: From the onset of the COVID pandemic in Uganda (May 2020), we found a significant reduction in the number of women accessing a fourth antenatal care visit (from APC + 183.5 to + 4.98; p < 0.001) and taking at least three doses of intermittent preventive treatment in pregnancy (IPTp, from APC + 84.28 to -63.12; p < 0.001). However, we found no significant change in the trend of the total number of pregnant women managed as outpatients or hospitalized for malaria, as well as in the number of women attending their first antenatal visit and in the number of institutional deliveries. CONCLUSIONS: In our study, the COVID-19 pandemic significantly reduced access to ANC visits and IPTp uptake. However, the healthcare system maintained its capacity for managing malaria cases, first antenatal visits, and institutional deliveries.Trial registration: This study has been registered on the ClinicalTrials.gov public website on 26 April 2022. ClinicalTrials.gov Identifier: NCT05348746.

Fetal Growth Retardation is Associated with High Apoptotic Cells and Low VEGF Expression in Placenta of Malarial Pregnant Mice.

Background: During pregnancy, pregnant women are susceptible to malaria, contributing significantly to maternal and infant mortality. Objective: This research was conducted to study the effect of Plasmodium berghei infection in pregnant mice on fetal growth retardation through placental cell apoptosis and the change of local vascularization. Methods: Eighteen pregnant Balb/c strain mice resulting from simultanously mating were divided into two groups those were nine pregnant mice used as non infected group and nine pregnant mice infected with Plasmodium berghei on day 9th post mating used as infected group respectively. On day 15th of post mating, all of the pregnant mice were killed. Fetal weights were measured using analytic balance. Apoptosis of placental cells and VEGF expression in the placental tissue were measured using immunohistochemistry. Results: Result showed that there was sequestration of parasite-infected red blood cells (PRBCs) in intervillous space. Statistical analysis showed that the fetal weights in infected pregnant mice group was significantly lower than non infected one (p = 0.01), and the placental cell apoptosis in placental tissue of infected pregnant mice was significantly higher than the non infected one (p=0.00).There was also a significant difference on VEGF expression between infected group and non infected group (p= 0,00). Conclusion: Plasmodium berghei infection in pregnant Balb/c mice can cause fetal growth retardation due to high of placental cell apoptosis and low VEGF expression.

Missed opportunities for Intermittent Preventive Treatment of Malaria among pregnant women with the recommended number of antenatal care visits in Nigeria: Secondary Analysis of Malaria Indicator Survey 2021.

BACKGROUND AND OBJECTIVES: Missed opportunity (MO) for IPTp SP remains high in Nigeria even among pregnant women with four or more ANC visits. We assessed the current MO rate and its predictors, using data from the 2021 MIS. METHODS: We carried out a secondary analysis of data of women who had at least one live birth and at least 4 ANC visits. Bivariate analyses assessed the relationship between socio-demographic characteristics, type of ANC facility, type of ANC provider, knowledge of malaria prevention, awareness about IPT, and missed opportunity using the Chi-square test. Multivariate analyses were presented as odd ratios at 95% CI, (P value <0.05). RESULTS: Nearly half (47%) had only primary education or none at all. About 30% were poor. Most had their 1st visit ANC in the 2nd trimester (58%). The missed opportunity rate was 55%. Predictors included age 20 to 34 years [aOR 1.3(1.1-1.67)], being very poor [aOR 1.6(1.1-2.4)], late ANC (in 2nd or 3rd trimester) [aOR 0.57(0.4-0.89)], ignorance about malaria prevention [aOR 1.8(1.4-2.4)], ignorance about IPT [aOR 1.3(1.3-2.5)] and residence in the South South and North East [aOR 0.46(0.31-0.68)] regions. CONCLUSIONS: The missed opportunity was high. Place of residence, poor knowledge of malaria prevention and IPT use, late commencement of ANC, poverty, and young age (20 to 34 years) contributed to the burden. Recommendations include stressing the importance of IPT during health talks. Provision of cups and drinking water for the IPT DOT policy by the Government and partners. There is a need for further research to unravel the reasons for the higher MO rates in some regions.

CONTEXTE: Les opportunités manquées (OM) pour le TPIp SP restent élevées au Nigéria, même parmi les femmes enceintes ayant effectué quatre visites ou plus aux soins prénatals. Nous avons évalué le taux actuel d'OM et ses prédicteurs en utilisant les données de l'Enquête sur les Indicateurs du Paludisme de 2021. MÉTHODE: Nous avons réalisé une analyse secondaire des données des femmes ayant eu au moins une naissance en vie et au moins quatre visites de soins prénatals. Les analyses bivariées ont évalué la relation entre les caractéristiques sociodémographiques, le type d'installation de soins prénatals, le type de prestataire de soins prénatals, la connaissance de la prévention du paludisme, la sensibilisation à propos du TPIp, et les opportunités manquées en utilisant le test du chi-carré. Les analyses multivariées ont été présentées sous forme de cotes ajustées avec un intervalle de confiance de 95 % (valeur de p<0,05). RÉSULTATS: Près de la moitié (47 %) avaient seulement une éducation primaire ou n'en avaient pas du tout. Environ 30 % étaient pauvres. La plupart ont effectué leur 1ère visite prénatale au cours du 2ème trimestre (58 %). Le taux d'opportunités manquées était de 55 %. Les prédicteurs comprenaient l'âge de 20 à 34 ans [aOR 1,3 (1,1-1,67)], être très pauvre [aOR 1,6 (1,1-2,4)], début tardif des soins prénatals (au 2ème ou 3ème trimestre) [aOR 0,57 (0,4-0,89)], ignorance de la prévention du paludisme [aOR 1,8 (1,4-2,4)], ignorance du TPIp [aOR 1,3 (1,3-2,5)] et résider dans les régions du Sud-Sud et du Nord-Est [aOR 0,46 (0,31-0,68)]. CONCLUSION: Les opportunités manquées étaient élevées. Le lieu de résidence, la méconnaissance de la prévention du paludisme et de l'utilisation du TPIp, le début tardif des soins prénatals, la pauvreté et l'âge jeune (20 à 34 ans) ont contribué à cette charge. Les recommandations incluent de souligner l'importance du TPIp lors des entretiens de santé. La fourniture de gobelets et d'eau potable pour la politique de l'administration directe du TPI par le gouvernement et les partenaires. Il est nécessaire de poursuivre la recherche pour découvrir les raisons des taux plus élevés d'OM dans certaines régions. Mots-clés: Paludisme pendant la grossesse, traitement préventif intermittent, sulfadoxine-pyriméthamine, opportunité manquée, soins prénatals.

Intestinal barrier disruption with Plasmodium falciparum infection in pregnancy and risk of preterm birth: a cohort study.

BACKGROUND: Malaria in early pregnancy is a risk factor for preterm birth and is associated with sustained inflammation and dysregulated angiogenesis across gestation. This study investigated whether malaria is associated with increased gut leak and whether this contributes to systemic inflammation, altered angiogenesis, and preterm birth. METHODS: We quantified plasma concentrations of gut leak markers, soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP) from 1339 HIV-negative pregnant Malawians at <24 weeks gestational age. We assessed the relationship of sCD14 and LBP concentrations with markers of inflammation, angiogenesis, and L-arginine bioavailability and compared them between participants with and without malaria, and with and without preterm birth. FINDINGS: Plasma concentrations of sCD14 and LBP were significantly higher in participants with malaria and were associated with parasite burden (p <0.0001, both analyses and analytes). The odds ratio for preterm birth associated with one log sCD14 was 2.67 (1.33 to 5.35, p = 0.006) and 1.63 (1.07-2.47, p = 0.023) for LBP. Both gut leak analytes were positively associated with increases in proinflammatory cytokines CRP, sTNFR2, IL18-BP, CHI3L1 and Angptl3 (p <0.05, all analytes) and sCD14 was significantly associated with angiogenic proteins Angpt-2, sENG and the sFLT:PlGF ratio (p <0.05, all analytes). sCD14 was negatively associated with L-arginine bioavailability (p <0.001). INTERPRETATION: Malaria in early pregnancy is associated with intestinal barrier dysfunction, which is linked to an increased risk of preterm birth. FUNDING: Open Philanthropy, Canadian Institutes of Health Research, Canada Research Chair program, European and Developing Countries Clinical Trials Partnership, Bill & Melinda Gates Foundation.

Interventions for malaria prevention in pregnancy; factors influencing uptake and their effect on pregnancy outcomes among post-natal women in a tertiary facility in the Volta Region of Ghana.

Objectives: Malaria in pregnancy is associated with adverse pregnancy outcomes including maternal anaemia and low birthweight. Uptake of preventive interventions is sub-optimal in sub-Saharan Africa including Ghana. Understanding local-level factors that influence uptake of these interventions can enhance control. The study assessed uptake of intermittent preventive treatment of malaria during pregnancy using sulphadoxine-pyrimethamine (IPTp-SP) and insecticide-treated net (ITN) use, their determinants and effects on pregnancy outcomes. Methods: A cross-sectional study involving 349 post-partum women was conducted from 25 August 2022 to 9 October 2022 at the Ho Teaching Hospital. A structured questionnaire was used to collect data on participant socio-demographics, ITN use, number of doses of sulphadoxine-pyrimethamine received, knowledge of malaria in pregnancy, haemoglobin levels and birth weight among others. Summary statistics were reported as frequencies, percentages and means. Associations between exposure and outcome variables were assessed using logistic regression methods and odds ratios reported with 95% confidence intervals. Statistical significance was concluded at p < 0.05. Results: More than 80% (291) of respondents received ⩾3 doses of intermittent preventive treatment using sulphadoxine-pyrimethamine and 64.8% (226) slept under ITNs the night before the survey. Age >25 years, employment, good knowledge of malaria in pregnancy, parity ⩾2 and initiating antenatal care visits in the first trimester facilitated the uptake of these interventions. Receiving ⩾3 doses of sulphadoxine-pyrimethamine was associated with having normal-weight babies (adjusted odds ratio 2.80, 95% CI: 1.07, 7.34; p = 0.036) while ITN use was associated with having term babies (adjusted odds ratio 2.72, 95% CI: 1.24, 5.90; p = 0.013) and normal maternal haemoglobin concentration at term (adjusted odds ratio 1.57, 95% CI: 1.01, 2.47; p = 0.044). Conclusions: The interventions were beneficial against low birthweight and preterm births which predispose to neonatal deaths and poor cognitive function in children. Malaria in pregnancy health campaigns should be intensified, especially among younger-aged primigravidae, to increase their knowledge of the condition as a way to further improve uptake of these preventive interventions.

Complement System Activation Is a Plasma Biomarker Signature during Malaria in Pregnancy.

Malaria in pregnancy (MiP) is a public health problem in malaria-endemic areas, contributing to detrimental outcomes for both mother and fetus. Primigravida and second-time mothers are most affected by severe anemia complications and babies with low birth weight compared to multigravida women. Infected erythrocytes (IE) reach the placenta, activating the immune response by placental monocyte infiltration and inflammation. However, specific markers of MiP result in poor outcomes, such as low birth weight, and intrauterine growth restriction for babies and maternal anemia in women infected with Plasmodium falciparum are limited. In this study, we identified the plasma proteome signature of a mouse model infected with Plasmodium berghei ANKA and pregnant women infected with Plasmodium falciparum infection using quantitative mass spectrometry-based proteomics. A total of 279 and 249 proteins were quantified in murine and human plasma samples, of which 28% and 30% were regulated proteins, respectively. Most of the regulated proteins in both organisms are involved in complement system activation during malaria in pregnancy. CBA anaphylatoxin assay confirmed the complement system activation by the increase in C3a and C4a anaphylatoxins in the infected plasma compared to non-infected plasma. Moreover, correlation analysis showed the association between complement system activation and reduced head circumference in newborns from Pf-infected mothers. The data obtained in this study highlight the correlation between the complement system and immune and newborn outcomes resulting from malaria in pregnancy.

Women's empowerment and uptake of sulfadoxine-pyrimethamine for intermittent preventive treatment of malaria during pregnancy: results from a cross-sectional baseline survey in the Lake endemic region, Kenya.

BACKGROUND: Malaria in pregnancy remains a major public health problem in endemic areas of the sub-Saharan African (SSA) region. However, there is limited understanding of the association between women's empowerment and the uptake of sulfadoxine-pyrimethamine for intermittent preventive treatment of malaria during pregnancy (IPTp-SP) in Kenya. This study examines the association between women's empowerment indicators (decision-making power, control of assets, education, and employment status) and the uptake of three or more doses of IPTp-SP in the Lake endemic region of Kenya. METHODS: The analysis utilized a dataset from a cross-sectional baseline survey of 3129 women aged 15-49 years in Kisumu and Migori Counties who had a live birth within the last 2 years preceding the study. Data were collected between June to August 2021. A descriptive analysis was conducted to show the distribution of respondents by key background characteristics, and bivariate and multivariate logistic regression to examine statistically significant associations between women's empowerment measures and the uptake of 3+ doses of IPTp-SP. RESULTS: Among the 3129 women surveyed, 1978 (65.7%) received 3+ doses of IPTp-SP during their most recent pregnancy. Controlling for individual characteristics and the number of ANC visits, the odds of taking 3+ doses of IPTp-SP increased among women who had high decision-making autonomy (AOR = 2.33; CI = 1.81-3.01; P < 0.001); and tertiary level of educational attainment (AOR = 1.51; CI = 1.10-2.06). However, the association between control of assets and uptake of IPTp-SP was positive but not statistically significant. CONCLUSION: Women's decision-making autonomy and educational attainment were positively associated with the uptake of IPTp-SP. As a result, maternal health interventions should focus on less empowered women, specifically those with less decision-making autonomy and no/low formal education, as they are less likely to achieve optimal uptake of IPTp-SP during pregnancy.

Malaria Infections and Placental Blood Flow: A Doppler Ultrasound Study From a Preconception Cohort in Benin.

Background: Malaria in pregnancy (MiP) has been associated with fetal growth restriction, the underlying pathogenic mechanisms of which remain poorly understood. Malaria in pregnancy is suspected to induce abnormalities in placental vascularization, leading to impaired placental development. Our study evaluated MIP's effect on uterine artery (UtA) and umbilical artery (UA) blood flow. Methods: The analysis included 253 Beninese women followed throughout pregnancy and screened monthly for submicroscopic and microscopic malaria. Uterine artery Doppler measurement was performed once between 21 and 25 weeks' gestation (wg), and UA Doppler measurement was performed 1-3 times from 28 wg. Linear and logistic regression models were used to assess the effect of malaria infections on UtA Doppler indicators (pulsatility index and presence of a notch), whereas a logistic mixed model was used to assess the association between malaria infections and abnormal UA Doppler (defined as Z-score ≥2 standard deviation or absent/reversed UA end-diastolic flow). Results: Primigravidae represented 7.5% of the study population; 42.3% of women had at least 1 microscopic infection during pregnancy, and 29.6% had at least 1 submicroscopic infection (and no microscopic infection). Both microscopic and submicroscopic infections before Doppler measurement were associated with the presence of a notch (adjusted odds ratio [aOR] 4.5, 95% confidence interval [CI] = 1.2-16.3 and aOR 3.3, 95% CI = .9-11.9, respectively). No associations were found between malaria before the Doppler measurement and abnormal UA Doppler. Conclusions: Malaria infections in the first half of pregnancy impair placental blood flow. This highlights the need to prevent malaria from the very beginning of pregnancy.

Fetal growth and birth weight are independently reduced by malaria infection and curable sexually transmitted and reproductive tract infections in Kenya, Tanzania, and Malawi: A pregnancy cohort study.

OBJECTIVES: Malaria and sexually transmitted and reproductive tract infections (STIs/RTIs) are highly prevalent in sub-Saharan Africa and associated with poor pregnancy outcomes. We investigated the individual and combined effects of malaria and curable STIs/RTIs on fetal growth in Kenya, Tanzania, and Malawi. METHODS: This study was nested within a randomized trial comparing monthly intermittent preventive treatment for malaria in pregnancy with sulfadoxine-pyrimethamine vs dihydroartemisinin-piperaquine, alone or combined with azithromycin. Fetal weight gain was assessed by serial prenatal ultrasound. Malaria was assessed monthly, and Treponema pallidum, Neisseria gonorrhoeae, Trichomonas vaginalis, Chlamydia trachomatis, and bacterial vaginosis at enrollment and in the third trimester. The effect of malaria and STIs/RTIs on fetal weight/birthweight Z-scores was evaluated using mixed-effects linear regression. RESULTS: In total, 1435 pregnant women had fetal/birth weight assessed 3950 times. Compared to women without malaria or STIs/RTIs (n = 399), malaria-only (n = 267), STIs/RTIs only (n = 410) or both (n = 353) were associated with reduced fetal growth (adjusted mean difference in fetal/birth weight Z-score [95% confidence interval]: malaria = -0.18 [-0.31,-0.04], P = 0.01; STIs/RTIs = -0.14 [-0.26,-0.03], P = 0.01; both = -0.20 [-0.33,-0.07], P = 0.003). Paucigravidae experienced the greatest impact. CONCLUSION: Malaria and STIs/RTIs are associated with poor fetal growth especially among paucigravidae women with dual infections. Integrated antenatal interventions are needed to reduce the burden of both malaria and STIs/RTIs.

The economic costs of malaria in pregnancy: evidence from four sub-Saharan countries.

Background Malaria in pregnancy is a major public health problem in sub-Saharan Africa (SSA), which imposes a significant economic burden. We provide evidence on the costs of malaria care in pregnancy to households and the health system in four high-burden countries in SSA.  Methods Household and health system economic costs associated with malaria control in pregnancy were estimated in selected areas of the Democratic Republic of Congo (DRC), Madagascar (MDG), Mozambique (MOZ) and Nigeria (NGA). An exit survey was administered to 2,031 pregnant women when leaving the antenatal care (ANC) clinic from October 2020 to June 2021. Women reported the direct and indirect costs associated to malaria prevention and treatment in pregnancy. To estimate health system costs, we interviewed health workers from 133 randomly selected health facilities. Costs were estimated using an ingredients-based approach. Results Average household costs of malaria prevention per pregnancy were USD6.33 in DRC, USD10.06 in MDG, USD15.03 in MOZ and USD13.33 in NGA. Household costs of treating an episode of uncomplicated/complicated malaria were USD22.78/USD46 in DRC, USD16.65/USD35.65 in MDG, USD30.54/USD61.25 in MOZ and USD18.92/USD44.71 in NGA, respectively. Average health system costs of malaria prevention per pregnancy were USD10.74 in DRC, USD16.95 in MDG, USD11.17 in MOZ and USD15.64 in NGA. Health system costs associated with treating an episode of uncomplicated/complicated malaria were USD4.69/USD101.41 in DRC, USD3.61/USD63.33 in MDG, USD4.68/USD83.70 in MOZ and USD4.09/USD92.64 in NGA. These estimates resulted in societal costs of malaria prevention and treatment per pregnancy of USD31.72 in DRC, USD29.77 in MDG, USD31.98 in MOZ and USD46.16 in NGA. Conclusions Malaria in pregnancy imposes a high economic burden on households and the health system. Findings emphasize the importance of investing in effective strategies that improve access to malaria control and reduce the burden of the infection in pregnancy.

Using Andersen's behavioral model of health care use for intermittent preventive treatment of malaria in pregnancy in Nigeria.

BACKGROUND: Studies in Nigeria and elsewhere in sub-Saharan Africa (sSA) have explored factors influencing usage of intermittent preventive treatment of malaria in pregnancy (IPTp). Most studies, however, are not model or theory-based, which provides less satisfactory guidance to malaria control programming. This study fills the knowledge gap by adapting Andersen's behavioral model of health care use to IPTp usage in Nigeria. METHODS: This study adopted a cross-sectional design that utilized secondary data extracted from the 2018 Nigeria Demographic and Health Survey (NDHS). A weighted sample of 4,772 women who had given birth in the past year preceding the survey, was analyzed. Outcome variable was usage of IPTp, dichotomized into optimal or otherwise. Explanatory variables cut across individual and community levels and were divided into predisposing, enabling and need factors in line with the theoretical constructs of the Andersen model. Two multilevel mixed-effects logistic regression models were fitted to identify factors which influenced optimal usage of IPTp. Analyses were performed using STATA 14. Statistical significance was set at 5%. RESULTS: Realised level of optimal IPTp usage was 21.8%. Factors that either predispose or enable pregnant women to take optimal doses of IPTp were maternal education, being employed, being autonomous in their own healthcare, health insurance enrolment, partner education, receiving antenatal care in public health facilities, rural residence, being resident in northern geo-political zones, community literacy level and community perception of the consequences of malaria. Two significant need factors affecting optimal usage of IPTp were timing of the first antenatal care visit and sleeping under mosquito bed nets. CONCLUSION: Optimal usage of IPTp is low among pregnant women in Nigeria. There is a need to devise additional public health educational programs promoting IPTp usage through the formation of Advocacy, Communication and Social Mobilisation (ACSM) in every ward in all local government areas, particularly in the rural and northern parts of the country. In addition, health planners should adopt the Andersen model for assessing key determinants of IPTp usage among childbearing women in Nigeria.

Keeping the momentum: suggestions for treatment policy updates in the final push to eliminate malaria in India.

Malaria case management with prompt and effective treatment is critical to minimize morbidity and mortality, reduce transmission and to prevent the emergence and spread of anti-malarial drug resistance. India has the highest burden of malaria in South East Asia Region and has made impressive progress in the reduction of the malaria burden in recent years. Since the last revision to the Indian national malaria treatment policy in 2013, guidelines on new treatment strategies have been published for the control/ elimination of malaria by the World Health Organisation (WHO). The most recent update was in March 2023 based on the new evidence available. India's success is the Region's success. Therefore, to meet the national as well as regional targets of elimination, the Indian National Programme needs to consider WHO guidelines, deliberate with stakeholders and experts so as to tailor and adapt to the local context, and update National policies to incorporate the relevant ones. Technical aspects of new WHO guidelines which need to be considered for updating India's treatment policy are discussed.