Trem2/Syk/PI3K axis contributes to the host protection against Toxoplasma gondii-induced adverse pregnancy outcomes via modulating decidual macrophages.

Decidual macrophages residing at the maternal-fetal interface have been recognized as pivotal factors for maintaining normal pregnancy; however, they are also key target cells of Toxoplasma gondii (T. gondii) in the pathology of T. gondii-induced adverse pregnancy. Trem2, as a functional receptor on macrophage surface, recognizes and binds various kinds of pathogens. The role and underlying mechanism of Trem2 in T. gondii infection remain elusive. In the present study, we found that T. gondii infection downregulated Trem2 expression and that Trem2-/- mice exhibited more severe adverse pregnancy outcomes than wildtype mice. We also demonstrated that T. gondii infection resulted in increased decidual macrophages, which were significantly reduced in the Trem2-/- pregnant mouse model as compared to wildtype control animals. We further described the inhibited proliferation, migration, and invasion functions of trophoblast cell by T. gondii antigens through macrophages as an "intermediate bridge", while this inhibition can be rescued by Trem2 agonist HSP60. Concurrently, Trem2 deficiency in bone marrow-derived macrophages (BMDMs) heightened the inhibitory effect of TgAg on the migration and invasion of trophoblast cells, accompanied by higher pro-inflammatory factors (IL-1ß, IL-6 and TNF-α) but a lower chemokine (CXCL1) in T. gondii antigens-treated BMDMs. Furthermore, compelling evidence from animal models and in vitro cell experiments suggests that T. gondii inhibits the Trem2-Syk-PI3K signaling pathway, leading to impaired function of decidual macrophages. Therefore, our findings highlight Trem2 signaling as an essential pathway by which decidual macrophages respond to T. gondii infection, suggesting Trem2 as a crucial sensor of decidual macrophages and potential therapeutic target in the pathology of T. gondii-induced adverse pregnancy.

Maternal Helminth Infection Causes Dysfunctional B Cell Development in Male Offspring.

Infections during pregnancy are known to trigger alterations in offspring immunity, often leading to increased disease susceptibility. Maternal helminth infections correlate with lower Ab titers to certain childhood immunizations and putative decreased vaccine efficacy. The mechanisms that underlie how maternal infection blunts offspring humoral responses are unclear. Using our murine model of maternal schistosomiasis, we found that maternal helminth infection decreases the germinal center response of all offspring to tetanus immunization. However, only male offspring have defects in memory B cell and long-lived plasma cell generation. We found this sex-specific aberration begins during B cell development within the bone marrow via alteration of the IL-7 niche and persists throughout antigenic activation in the germinal center in the periphery. Critically, these defects in males are cell intrinsic, persisting following adoptive transfer to control male pups. Together, these data show that maternal infections can alter both the bone marrow microenvironment and the development of B lymphocytes in a sex-specific manner. This study correlates maternal infection induced defects in early life B cell development with ineffective Ab responses after vaccination.

Effect of monthly intermittent preventive treatment with dihydroartemisinin-piperaquine with and without azithromycin versus monthly sulfadoxine-pyrimethamine on adverse pregnancy outcomes in Africa: a double-blind randomised, partly placebo-controlled trial.

BACKGROUND: Intermittent preventive treatment in pregnancy (IPTp) with dihydroartemisinin-piperaquine is more effective than IPTp with sulfadoxine-pyrimethamine at reducing malaria infection during pregnancy in areas with high-grade resistance to sulfadoxine-pyrimethamine by Plasmodium falciparum in east Africa. We aimed to assess whether IPTp with dihydroartemisinin-piperaquine, alone or combined with azithromycin, can reduce adverse pregnancy outcomes compared with IPTp with sulfadoxine-pyrimethamine. METHODS: We did an individually randomised, double-blind, three-arm, partly placebo-controlled trial in areas of high sulfadoxine-pyrimethamine resistance in Kenya, Malawi, and Tanzania. HIV-negative women with a viable singleton pregnancy were randomly assigned (1:1:1) by computer-generated block randomisation, stratified by site and gravidity, to receive monthly IPTp with sulfadoxine-pyrimethamine (500 mg of sulfadoxine and 25 mg of pyrimethamine for 1 day), monthly IPTp with dihydroartemisinin-piperaquine (dosed by weight; three to five tablets containing 40 mg of dihydroartemisinin and 320 mg of piperaquine once daily for 3 consecutive days) plus a single treatment course of placebo, or monthly IPTp with dihydroartemisinin-piperaquine plus a single treatment course of azithromycin (two tablets containing 500 mg once daily for 2 consecutive days). Outcome assessors in the delivery units were masked to treatment group. The composite primary endpoint was adverse pregnancy outcome, defined as fetal loss, adverse newborn baby outcomes (small for gestational age, low birthweight, or preterm), or neonatal death. The primary analysis was by modified intention to treat, consisting of all randomised participants with primary endpoint data. Women who received at least one dose of study drug were included in the safety analyses. This trial is registered with ClinicalTrials.gov, NCT03208179. FINDINGS: From March-29, 2018, to July 5, 2019, 4680 women (mean age 25·0 years [SD 6·0]) were enrolled and randomly assigned: 1561 (33%; mean age 24·9 years [SD 6·1]) to the sulfadoxine-pyrimethamine group, 1561 (33%; mean age 25·1 years [6·1]) to the dihydroartemisinin-piperaquine group, and 1558 (33%; mean age 24·9 years [6.0]) to the dihydroartemisinin-piperaquine plus azithromycin group. Compared with 335 (23·3%) of 1435 women in the sulfadoxine-pyrimethamine group, the primary composite endpoint of adverse pregnancy outcomes was reported more frequently in the dihydroartemisinin-piperaquine group (403 [27·9%] of 1442; risk ratio 1·20, 95% CI 1·06-1·36; p=0·0040) and in the dihydroartemisinin-piperaquine plus azithromycin group (396 [27·6%] of 1433; 1·16, 1·03-1·32; p=0·017). The incidence of serious adverse events was similar in mothers (sulfadoxine-pyrimethamine group 17·7 per 100 person-years, dihydroartemisinin-piperaquine group 14·8 per 100 person-years, and dihydroartemisinin-piperaquine plus azithromycin group 16·9 per 100 person-years) and infants (sulfadoxine-pyrimethamine group 49·2 per 100 person-years, dihydroartemisinin-piperaquine group 42·4 per 100 person-years, and dihydroartemisinin-piperaquine plus azithromycin group 47·8 per 100 person-years) across treatment groups. 12 (0·2%) of 6685 sulfadoxine-pyrimethamine, 19 (0·3%) of 7014 dihydroartemisinin-piperaquine, and 23 (0·3%) of 6849 dihydroartemisinin-piperaquine plus azithromycin treatment courses were vomited within 30 min. INTERPRETATION: Monthly IPTp with dihydroartemisinin-piperaquine did not improve pregnancy outcomes, and the addition of a single course of azithromycin did not enhance the effect of monthly IPTp with dihydroartemisinin-piperaquine. Trials that combine sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine for IPTp should be considered. FUNDING: European & Developing Countries Clinical Trials Partnership 2, supported by the EU, and the UK Joint-Global-Health-Trials-Scheme of the Foreign, Commonwealth and Development Office, Medical Research Council, Department of Health and Social Care, Wellcome, and the Bill-&-Melinda-Gates-Foundation.

Malaria in pregnancy: baby steps.

PURPOSE OF REVIEW: Malaria threatens pregnant women and their babies, particularly in Africa. RECENT FINDINGS: This century, the number of women at risk of malaria in pregnancy has decreased globally, apart from in Africa, where it has increased. Low and sub microscopic infections are increasingly documented but remain hard to diagnose with current point-of-care tests, and their contribution to morbidity and transmission are unclear. Artemether-lumefantrine has been endorsed for treatment in first trimester, but many women attend antenatal clinics later in pregnancy, and reaching high-risk young, first-time mothers is particularly difficult. Small-for-gestational-age babies frequently result from malaria, which affects the placenta's development and its functions such as nutrient transport. Resistance to continues to increase to sulphadoxine-pyrimethamine, the mainstay of intermittent preventive treatment in pregnancy. The alternative, dihydroartemisinin-piperaquine controls malaria better, but does not improve pregnancy outcomes, suggesting that sulphadoxine-pyrimethamine may have nonmalarial effects including improving gut function or reducing dangerous inflammation. Understanding of how the malaria parasite uses the VAR2CSA protein to bind to its placental receptor is increasing, informing the search for a vaccine to prevent pregnancy malaria. SUMMARY: Progress in several areas increases optimism that improved prevention and control of malaria in pregnancy is possible, but obstacles remain.

The prevention of congenital toxoplasmosis using a combination of Spiramycin and Cotrimoxazole: The long-time experience of a tertiary referral centre.

BACKGROUND: Toxoplasmosis is a parasitic infection caused by Toxoplasma gondii and is responsible for gestational and congenital infections worldwide. The current standard therapy is based on the administration of Spiramycin to prevent trans-placental transmission. Other therapies are being studied to reduce the rates of foetal transmission and symptomatic congenital infection. OBJECTIVES: We report our long-standing experience in maternal toxoplasmosis infection treatment using a combination of Spiramycin-Cotrimoxazole, assessing its effectiveness in preventing vertical transmission compared to the expected incidence of congenital infection. METHODS: We retrospectively collected cases of pregnant women referred to our centre for suspected toxoplasmosis infection according to Lebech criteria, treated with Spiramycin-Cotrimoxazole. RESULTS: Of 1364 women referred to our centre, postnatal follow-up of primary toxoplasmosis was available in 562 cases (73.9%). The overall vertical transmission rate was 3.4% in women treated immediately with Spiramycin-Cotrimoxazole after the diagnosis of infection. In comparison, it was 7.7% in women undergoing the same therapy but late or with poor compliance. The foetal transmission rate was 71.4% in untreated cases. All the infected newborns of mother treated adequately with Spiramycin-Cotrimoxazole were asymptomatic afterbirth, while 6/21 infected infants of the inadequate Spiramycin-Cotrimoxazole therapy group had postnatal sequelae (28.5%). The incidence of transmission after appropriate Spiramycin-Cotrimoxazole therapy was significantly lower than the expected rate reported in literature. CONCLUSIONS: A combination of Spiramycin and Cotrimoxazole is safe and effective in preventing foetal congenital toxoplasmosis and reducing sequelae in case of in-utero infection. The timing and adherence to the therapy are crucial to lowering the risk of congenital infection and neonatal morbidity.

Lifestyles associated with malaria in pregnancy in northwest Colombia: a mixed study from Latin American critical epidemiology.

BACKGROUND: In the scientific literature on Malaria in Pregnancy (MiP), no studies have been conducted on lifestyles based on critical theory. The objective of this study was to analyse the lifestyles or singular processes of social determination of health in MiP in northwestern Colombia. METHODS: Mixed QUAN-QUAL convergent triangulation study. In the quantitative component, a psychometric evaluation and a cross-sectional design were conducted in 400 pregnant women to whom the Pender-Walker lifestyle scale and a survey on MiP prevention were applied. In the qualitative study, a critical ethnography was conducted with 46 pregnant women in whom their narratives and practices regarding lifestyles at home and healthcare were described. RESULTS: The frequency of MiP was 9%, and a higher occurrence of the disease was identified in those who did not control stagnant water (29%), did not use insecticide-treated net (16%) and went to the hospital (14%) or the microscopist (20%) when they had fever. This coincides with the presence of unhealthy lifestyles, little knowledge about malaria, and a low perception of the risk of getting sick, as well as meanings and experiences about MiP, maternity, and pregnancy that show a high clinical, cultural, and socioeconomic burden for the women studied. CONCLUSION: This epidemiological profile and the approach to lifestyles based on the postulates of critical theory in health evidence that pregnant women exposed to malaria suffer serious social, cultural and health injustices that are not possible to impact with the current health model of malaria control in Colombia guided by aetiopathogenic, biomedical, positivist and utilitarian theories.

IgG and IgM responses to the Plasmodium falciparum asexual stage antigens reflect respectively protection against malaria during pregnancy and infanthood.

BACKGROUND: Plasmodium falciparum malaria is a public health issue mostly seen in tropical countries. Until now, there is no effective malaria vaccine against antigens specific to the blood-stage of P. falciparum infection. Because the pathogenesis of malarial disease results from blood-stage infection, it is essential to identify the most promising blood-stage vaccine candidate antigens under natural exposure to malaria infection. METHODS: A cohort of 400 pregnant women and their infants was implemented in South Benin. An active and passive protocol of malaria surveillance was established during pregnancy and infancy to precisely ascertain malaria infections during the follow-up. Twenty-eight antibody (Ab) responses specific to seven malaria candidate vaccine antigens were repeatedly quantified during pregnancy (3 time points) and infancy (6 time points) in order to study the Ab kinetics and their protective role. Abs were quantified by ELISA and logistic, linear and cox-proportional hazard model were performed to analyse the associations between Ab responses and protection against malaria in mothers and infants, taking into account socio-economic factors and for infants an environmental risk of exposure. RESULTS: The levels of IgM against MSP1, MSP2 and MSP3 showed an early protective response against the onset of symptomatic malaria infections starting from the 18th month of life, whereas no association was found for IgG responses during infancy. In women, some IgG responses tend to be associated with a protection against malaria risk along pregnancy and at delivery, among them IgG3 against GLURP-R0 and IgG2 against MSP1. CONCLUSION: The main finding suggests that IgM should be considered in vaccine designs during infanthood. Investigation of the functional role played by IgM in malaria protection needs further attention.

Prospective study of malaria in pregnancy, placental and congenital malaria in Northwest Colombia.

BACKGROUND: Pregnancy Associated Malaria (PAM) include malaria in pregnancy (MiP), placental malaria (PM), and congenital malaria (CM). The evidence available in Colombia on PAM focuses on one of the presentations (MiP, PM or CM), and no study longitudinally analyses the infection from the pregnant woman, passing through the placenta, until culminating in the newborn. This study determined the frequency of MiP, PM, and CM caused by Plasmodium vivax, Plasmodium falciparum, or mixed infections, according to Thick Blood Smear (TBS) and quantitative Polymerase Chain Reaction (qPCR). Identifying associated factors of PAM and clinical-epidemiological outcomes in northwestern Colombia. METHODS: Prospective study of 431 pregnant women, their placenta, and newborns registered in the data bank of the research Group "Salud y Comunidad César Uribe Piedrahíta" which collected information between 2014 and 2020 in endemic municipalities of the departments of Córdoba and Antioquia. The frequency of infection was determined with 95% confidence intervals. Comparisons were made with the Chi-square test, Student t-test, prevalence ratios, and control for confounding variables by log-binomial regression. RESULTS: The frequency of MiP was 22.3% (4.6% using TBS), PM 24.8% (1.4% using TBS), and CM 11.8% (0% using TBS). Using TBS predominated P. vivax. Using qPCR the proportions of P. vivax and P. falciparum were similar for MiP and PM, but P. falciparum predominated in CM. The frequency was higher in nulliparous, and women with previous malaria. The main clinical effects of PAM were anaemia, low birth weight, and abnormal APGAR score. CONCLUSIONS: The magnitude of infections was not detected with TBS because most cases were submicroscopic (TBS-negative, qPCR-positive). This confirmed the importance of improving the molecular detection of cases. PAM continue being underestimated in the country due to that in Colombia the control programme is based on TBS, despite its outcomes on maternal, and congenital health.

Uptake of intermittent preventive treatment of malaria in pregnancy and risk factors for maternal anaemia and low birthweight among HIV-negative mothers in Dschang, West region of Cameroon: a cross sectional study.

BACKGROUND: Approximately 32 million pregnant women are at risk of malaria with up to 10,000 maternal deaths and 200,000 neonates at risk annually. Intermittent Preventive Treatment (IPT) with sulfadoxine-pyrimethamine (SP) is recommended by the World Health Organization (WHO) to reduce disease in pregnancy and adverse maternal and newborn outcomes. At least three doses of SP should be taken by pregnant women during antenatal consultation (ANC) beginning from the thirteenth week of pregnancy till parturition. The aim of this study was to assess uptake of IPT during pregnancy and risk factors for maternal anaemia and infant birth weight in Dschang, West region of Cameroon. METHODS: A total of 380 consenting pregnant women at delivery were recruited in a cross- sectional prospective survey between January to December 2021. Data on ANC attendance, total dose of IPT and history of malaria were abstracted from hospital ANC records while socio-demographic characteristics, bed net use and obstetrics history of each participant were also recorded through an interview. Further, blood samples were collected from the intervillous space for assessment of maternal anaemia and microscopic parasitology. Nested PCR based on amplification of the Plasmodium 18S sRNA was carried out to detect submicroscopic infection. IPTp coverage was calculated per WHO recommendation and the prevalence of anaemia and low birth weight were estimated as proportions in the total sample of pregnant women and live births, respectively. Crude and adjusted odds ratios and their 95% confidence intervals were used to estimate associations between pregnancy outcomes considered and risk factors in specific and general models. A p < 0.05 was considered significant. The R software (V4.1.4) was used for all analyses. RESULTS: A majority of pregnant women was aged between 24 and 34 years old (59.2%) and had secondary education (58.8%). Uptake of ≥ 3 IPTp was 64.99% with 77.20% of all who received at least one IPTp doses taking a mix of SP and DP or DP alone in successive ANC contacts. Those with four or more ANC contacts (73.42%) were more likely to have received at least one IPTp. Furthermore, 13.9% of live births had low birthweights (BW < 2500 g) and one in four parturient women with moderate anaemia by WHO criteria. Microscopy (blood smear examination) and PCR-based diagnosis revealed between 0% and 1.57% of parasite-infected placental samples, respectively. Reported malaria in pregnancy predicted maternal anaemia at birth but not birth weight. Only gestational age (< 37 weeks) and bed net use (< 5 months) significantly predicted infant birth weight at delivery. CONCLUSION: The uptake of WHO recommended IPT doses during pregnancy was moderately high. Reported malaria in pregnancy, poor bed net coverage, gestational age less than 37 weeks adversely affect maternal haemoglobin levels at birth and infant birth weight. Asymptomatic and submicroscopic placental parasite infections was found at low prevalence. Together these results highlight the importance of maintaining aggressive measures to prevent malaria in pregnancy and protect the health of mother and baby.

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.

WHO antenatal care policy and prevention of malaria in pregnancy in sub-Saharan Africa.

BACKGROUND: The WHO 2016 antenatal care (ANC) policy recommends at least eight antenatal contacts during pregnancy. This study assessed ANC8 uptake following policy implementation and explored the relationship between ANC attendance and intermittent preventive treatment in pregnancy (IPTp) coverage in sub-Saharan Africa following the rollout of the World Health Organization (WHO) 2016 ANC policy, specifically, to assess differences in IPTp uptake between women attending eight versus four ANC contacts. METHODS: A secondary analysis of data from 20 sub-Saharan African countries with available Demographic Health and Malaria Indicator surveys from 2018 to 2023 was performed. The key variables were the number of ANC contacts and IPTp doses received during a participant's last completed pregnancy in the past two years. Pooled crude and multivariable logistic regression models were used to explore factors associated with attendance of at least four or eight ANC contacts as well as receipt of at least three doses of IPTp during pregnancy. RESULTS: Overall, only a small proportion of women (median = 3.9%) completed eight or more ANC contacts (ANC8 +). Factors significantly associated with increased odds of ANC8 + included early ANC attendance (AOR: 4.61: 95% CI 4.30-4.95), literacy (AOR: 1.20; 95% CI 1.11-1.29), and higher wealth quintile (AOR: 3.03; 95% CI 2.67-3.44). The pooled estimate across all countries showed a very slight increase in the odds of IPTp3 + among women with eight (AOR: 1.06; 95% CI 1.00-1.12) compared to those with four contacts. In all but two countries, having eight instead of four ANC contacts did not confer significantly greater odds of receiving three or more doses of IPTp (IPTp3 +), except in Ghana (AOR: 1.67; 95% CI 1.38-2.04) and Liberia (AOR: 1.43; 95% CI 1.18-1.72). CONCLUSION: Eight years after the WHO ANC policy recommendation, all countries still had sub-optimal ANC8 + coverage rates. This paper is a call to action to actualize the vision of the WHO and the global malaria community of a malaria free world. Policies to improve ANC and IPTp coverage should be operationalized with clear actionable guidance and local ownership. Study findings can be used to inform multi-level policy, programmatic, and research recommendations to optimize ANC attendance and malaria in pregnancy prevention, thus improving maternal and child health outcomes, including the reduction of malaria in pregnancy.

Impact on pregnancy outcomes of intermittent preventive treatment with sulfadoxine-pyrimethamine in urban and peri-urban Papua New Guinea: a retrospective cohort study.

BACKGROUND: Intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) reduces malaria-attributable adverse pregnancy outcomes and may also prevent low birth weight (< 2,500 g) through mechanisms independent of malaria. Malaria transmission in Papua New Guinea (PNG) is highly heterogeneous. The impact of IPTp-SP on adverse birth outcomes in settings with little or no malaria transmission, such as PNG's capital city Port Moresby, is unknown. METHODS: A retrospective cohort study was conducted amongst HIV-negative women with a singleton pregnancy who delivered at Port Moresby General Hospital between 18 July and 21 August 2022. The impact of IPTp-SP doses on adverse birth outcomes and anaemia was assessed using logistic and linear regression models, as appropriate. RESULTS: Of 1,140 eligible women amongst 1,228 consecutive births, 1,110 had a live birth with a documented birth weight. A total of 156 women (13.7%) did not receive any IPTp-SP, 347 women (30.4%) received one, 333 (29.2%) received two, and 304 (26.7%) received the recommended ≥ 3 doses of IPTp-SP. A total of 65 of 1,110 liveborn babies (5.9%) had low birth weight and there were 34 perinatal deaths (3.0%). Anaemia (haemoglobin < 100 g/L) was observed in 30.6% (243/793) of women, and 14 (1.2%) had clinical malaria in pregnancy. Compared to women receiving 0-1 dose of IPTp-SP, women receiving ≥ 2 doses had lower odds of LBW (adjusted odds ratio [aOR] 0.50; 95% confidence interval [CI] 0.26, 0.96), preterm birth (aOR 0.58; 95% CI 0.32, 1.04), perinatal death (aOR 0.49; 95% CI 0.18, 1.38), LBW/perinatal death (aOR 0.55; 95% CI 0.27, 1.12), and anaemia (OR 0.50; 95% CI 0.36, 0.69). Women who received 2 doses versus 0-1 had 45% lower odds of LBW (aOR 0.55, 95% CI 0.27, 1.10), and a 16% further (total 61%) reduction with ≥ 3 doses (aOR 0.39, 95% CI 0.14, 1.05). Birth weights for women who received 2 or ≥ 3 doses versus 0-1 were 81 g (95% CI -3, 166) higher, and 151 g (58, 246) higher, respectively. CONCLUSIONS: Provision of IPTp-SP in a low malaria-transmission setting in PNG appears to translate into substantial health benefits, in a dose-response manner, supporting the strengthening IPTp-SP uptake across all transmission settings in PNG.

Malaria in pregnancy: Meta-analyses of prevalence and associated complications.

This review aims to assess the prevalence of malaria in pregnancy during antenatal visits and delivery, species-specific burden together with regional variation in the burden of disease. It also aims to estimate the proportions of adverse pregnancy outcomes in malaria-positive women. Based on the PRISMA guidelines, a thorough and systematic search was conducted in July 2023 across two electronic databases (including PubMed and CENTRAL). Forest plots were constructed for each outcome of interest highlighting the effect measure, confidence interval, sample size, and its associated weightage. All the statistical meta-analysis were conducted using R-Studio version 2022.07. Sensitivity analyses, publication bias assessment, and meta-regression analyses were also performed to ensure robustness of the review. According to the pooled estimates of 253 studies, the overall prevalence of malaria was 18.95% (95% CI: 16.95-21.11), during antenatal visits was 20.09% (95% CI: 17.43-23.06), and at delivery was 17.32% (95% CI: 14.47-20.61). The highest proportion of malarial infection was observed in Africa approximating 21.50% (95% CI: 18.52-24.81) during ANC and 20.41% (95% CI: 17.04-24.24) at the time of delivery. Our analysis also revealed that the odds of having anaemia were 2.40 times (95% CI: 1.87-3.06), having low birthweight were 1.99 times (95% CI: 1.60-2.48), having preterm birth were 1.65 times (95% CI: 1.29-2.10), and having stillbirths were 1.40 times (95% CI: 1.15-1.71) in pregnant women with malaria.

Comparison of malaria diagnostic methods for detection of asymptomatic Plasmodium infections among pregnant women in northwest Ethiopia.

BACKGROUND: Malaria in pregnancy remains a major public health problem in the globe, especially in sub-Saharan Africa. In malaria endemic areas, most pregnant women remain asymptomatic, but malaria could still cause complications on the mother and her offspring; as well as serve as reservoirs to transmit infection. Despite these effects, no attention is given to the diagnosis of asymptomatic Plasmodium infections (APIs) using highly sensitive and specific laboratory diagnostic tools in Ethiopia. Therefore, the goal of this study was to compare the performance of Rapid Diagnostic Test (RDT), microscopy and real-time polymerase chain reaction (RT-PCR) to detect APIs among pregnant women. METHODS: A health facility based cross -sectional study was conducted among pregnant women attending antenatal care at Fendeka town health facilities Jawi district, northwest Ethiopia from February to March, 2019. A total of 166 participants were enrolled by using convenient sampling technique. Socio-demographic features were collected using a semi structured questionnaire. Dried blood spot (DBS) samples were collected for molecular analysis. Asymptomatic Plasmodium infection on pregnant women was diagnosed using RDT, microscopy and RT-PCR. Descriptive statistics were used to determine the prevalence of APIs. Method comparison was performed, and Cohen's kappa coefficient (k) was used to determine the degree of agreement among the diagnostic methods. Parasite densities were also calculated. RESULTS: The prevalence of API was 9.6%, 11.4% and 18.7% using RDT, microscopy and RT-PCR, respectively. The overall proportion of API was 19.3%. Sensitivity of the RDT was 83.3% as compared with microscopy. Rapid Diagnostic Test and microscopy also showed sensitivity of 50% and 60%, respectively, as compared with RT-PCR. The mean parasite density was 3213 parasites/µl for P falciparum and 1140 parasites/µl of blood for P. vivax. CONCLUSION: Prevalence of API in the study area was high. Both RDT and microscopy had lower sensitivity when compared with RT-PCR. Therefore, routine laboratory diagnosis of API among pregnant women should be given attention and done with better sensitive and specific laboratory diagnostic tools.

Prevalence and associated factors of schistosomiasis among pregnant women in northern Senegal.

BACKGROUND: Schistosomiasis remains a public health concern worldwide. It is responsible for more than 240 million cases in 78 countries, 40 million of whom are women of childbearing age. In the Senegal River basin, both Schistosoma haematobium and Schistosoma mansoni are very prevalent in school-age children. However, there is a lack of information on the burden of schistosomiasis in pregnant women, which can cause complications in the pregnancy outcome. This study aimed to determine the prevalence and associated factors of schistosomiasis in pregnant women. METHODS: We conducted a prospective cross-sectional study of pregnant women attending antenatal clinics at the health center of the Senegalese Sugar Company and at the hospital of Richard Toll between August and December 2021. The urine and stool samples collected were examined using microscopy techniques and quantitative polymerase chain reaction (qPCR) to detect the presence of S. haematobium and S. mansoni. The urines were previously tested using urine reagent strips to detect hematuria and proteinuria. Socio-demographical, clinical, and diagnostically data were recorded by the midwife and the gynaecologist. The data were analyzed using a logistic regression model. RESULTS: Among the 298 women examined for the infection by microscopic, 65 (21.81%) were infected with urogenital schistosomiasis, 10 (3.36%) with intestinal schistosomiasis, and 4 (1.34%) were co-infected with both types of schistosomiasis. Out of the 288 samples tested by qPCR, 146 (48.99%) were positive for S. haematobium, 49 (35.51%) for S. mansoni and 22 (15.94%) for both species (co-infection). Pregnant women having microscopic haematuria and proteinuria were significantly more infected (p < 0.05). CONCLUSION: This study has revealed a high prevalence of schistosomiasis in pregnant women in Senegal. The qPCR allowed us to detect more cases compared to the microscopy. There is a need to conduct more studies to understand the real burden of the disease and to set up a surveillance system to prevent pregnancy-related complications.

Soil-transmitted helminths and associated factors among pregnant women in Doreni district, Oromia region, Ethiopia: a cross-sectional study.

BACKGROUND: Soil-transmitted helminthiasis (STH) refers to a set of parasitic illnesses caused by nematode worms and spread to people through faeces-contaminated soil. It is highly prevalent in low- and middle-income countries due to a lack of environmental sanitation and personal hygiene. Pregnant women are among the risk groups for infection by soil-transmitted helminths. Former studies of the disease burden among pregnant women in Ethiopia didn't indicate the intensity of parasitic infection. The aim of this study was to assess the prevalence and associated factors of soil-transmitted helminths among pregnant women. METHODS: An institution-based cross-sectional study was conducted among 416 randomly selected pregnant women. The data were collected using a structured interview-administered questionnaire and a laboratory test. The Kato-Katz technique was used to diagnose soil-transmitted helminthiasis and determine the intensity of the infection. The collected data were entered into Epi-Data version 4.6 and exported to SPSS version 25 for analysis. Multivariate logistic regression analysis was used to identify independent predictors of soil-transmitted helminths at a p-value < 0.05. RESULTS: The overall prevalence of soil-transmitted helminths among pregnant women was 30%. (95%, CI: 26-34%). Living in a rural area (AOR = 3.35; 95% CI = 1.83-6.13), drinking from an unprotected water source (AOR = 2.52; 95% CI = 1.45-4.37), not washing one's hand after the toilet (AOR = 2.75; 95% CI = 1.55-4.88), lacking health information (AOR = 1.70; 95% CI = 1.01-2.85), working as a daily labourer (AOR = 2.88; 95% CI = 1.01-8.20), and walking barefoot (AOR = 4.00; 95% CI = 2.29-7.00) were significantly associated with the presence of soil-transmitted helminths among pregnant women. CONCLUSION: The prevalence of STH was significantly moderate in the study area, where pregnant women were mostly affected by ascariasis and hookworms. Living in a rural area, being a daily labourer, walking barefoot, not washing hands after the toilet, drinking from an unprotected water source, and lacking health information were the determining factors. Interventions including health education, the expansion of pure drinking water sources, the promotion of personal hygiene, and the wearing of shoes are recommended to reduce the burden of soil-transmitted helminths in the study area.

Altered Offspring Immunity in Maternal Parasitic Infections.

Maternal infection during pregnancy is known to alter the development and function of offspring's immune system, leading to inappropriate immune responses to common childhood infections and immunizations. Although this is an expanding field, maternal parasitic infections remain understudied. Millions of women of reproductive age are currently at risk for parasitic infection, whereas many pregnant, chronically infected women are excluded from mass drug administration due partially to a lack of resources, as well as fear of unknown adverse fetal developmental outcomes. In areas endemic for multiple parasitic infections, such as sub-Saharan Africa, there are increased rates of morbidity and mortality for various infections during early childhood in comparison with nonendemic areas. Despite evidence supporting similar immunomodulatory effects between various parasite species, there is no clear mechanistic understanding of how maternal infection reprograms offspring immunity. This brief review will compare the effects of selected maternal parasitic infections on offspring immunity.

Gastrointestinal nematode infection during pregnancy and lactation enhances spatial reference memory and reduces indicators of anxiety-like behaviour in uninfected adult female mouse offspring.

Maternal bacterial and viral infections that induce neuroinflammation in the developing brain are associated with impaired cognitive function and increased anxiety in the offspring. In contrast, maternal infection with the immunoregulatory murine gastrointestinal (GI) nematode, Heligmosomoides bakeri, appears to benefit neurodevelopment as juvenile 2- and 3-week-old male and female offspring had enhanced spatial memory, which may be due to a Th2/Treg biased neuroimmune environment. Here, the impact of maternal H. bakeri infection during pregnancy and lactation on the spatial and anxiety-like behaviours of adult, 3-month-old uninfected male and female offspring was explored for the first time. It was observed that adult female offspring of H. bakeri-infected dams had enhanced spatial reference memory and reduced anxiety-like behaviour compared to females of uninfected dams. These effects were not observed in adult male offspring. Thus, the positive influence of a maternal GI nematode infection on spatial memory of juvenile offspring persists in adult female offspring.

Intermittent preventive treatment regimens for malaria in HIV-positive pregnant women.

BACKGROUND: Malaria and HIV infection overlap geographically in sub-Saharan Africa and share risk factors. HIV infection increases malaria's severity, especially in pregnant women. The World Health Organization (WHO) recommends intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) for pregnant women living in areas of stable malaria transmission. However, HIV-positive women on daily cotrimoxazole prophylaxis (recommended for prevention of opportunistic infections in people with HIV) cannot receive SP due to adverse drug interactions, so malaria prevention in this vulnerable population currently relies on daily cotrimoxazole prophylaxis alone. This review is based on a new protocol and provides an update to the 2011 Cochrane Review that evaluated alternative drugs for IPTp to prevent malaria in HIV-positive women. OBJECTIVES: To compare the safety and efficacy of intermittent preventive treatment regimens for malaria prevention in HIV-positive pregnant women. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, three other databases, and two trial registries to 31 January 2024. To identify relevant additional studies or unpublished work, we checked references and contacted study authors and other researchers working on malaria and HIV. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing any intermittent preventive treatment regimen for preventing malaria in HIV-positive pregnant women against daily cotrimoxazole prophylaxis alone, placebo, current or previous standard of care, or combinations of these options. By 'standard of care' we refer to the country's recommended drug regimen to prevent malaria in pregnancy among HIV-positive women, or the treatment that a trial's research team considered to be the standard of care. DATA COLLECTION AND ANALYSIS: Review authors, in pairs, independently screened all records identified by the search strategy, applied inclusion criteria, assessed risk of bias in included trials, and extracted data. We contacted trial authors when additional information was required. We presented dichotomous outcomes using risk ratios (RRs), count outcomes as incidence rate ratios (IRRs), and continuous outcomes as mean differences (MDs). We presented all measures of effect with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach for what we considered to be the main comparisons and outcomes. MAIN RESULTS: We included 14 RCTs, with a total of 4976 HIV-positive pregnant women initially randomized. All trials assessed the efficacy and safety of one antimalarial used as IPTp (mefloquine, dihydroartemisinin/piperaquine, SP, or azithromycin) with or without daily cotrimoxazole, compared to daily cotrimoxazole alone, placebo, or a standard of care regimen. We grouped the trials into nine comparisons. Our main comparison evaluated the current standard of care (daily cotrimoxazole) with another drug regimen (mefloquine or dihydroartemisinin/piperaquine) versus daily cotrimoxazole with or without placebo. In this comparison, two trials evaluated mefloquine and three evaluated dihydroartemisinin/piperaquine. We conducted meta-analyses that included trials evaluating dihydroartemisinin/piperaquine plus cotrimoxazole, and trials that evaluated mefloquine plus cotrimoxazole, as we considered there to be no qualitative or quantitative heterogeneity among trials for most outcomes. We considered drug-related adverse events and HIV-related outcomes to be drug-specific. Daily cotrimoxazole prophylaxis plus another drug regimen (mefloquine or dihydroartemisinin/piperaquine) probably results in lower risk of maternal peripheral parasitaemia at delivery (RR 0.62, 95% CI 0.41 to 0.95; 2406 participants, 5 trials; moderate-certainty evidence). It results in little or no difference in maternal anaemia cases at delivery (RR 0.98, 95% CI 0.90 to 1.07; 2417 participants, 3 trials; high-certainty evidence). It probably results in a decrease in placental malaria measured by blood smear (RR 0.54, 95% CI 0.31 to 0.93; 1337 participants, 3 trials; moderate-certainty evidence), and probably results in little or no difference in low birth weight (RR 1.16, 95% CI 0.95 to 1.41; 2915 participants, 5 trials; moderate-certainty evidence). There is insufficient evidence to ascertain whether daily cotrimoxazole prophylaxis plus another drug regimen affects the risk of cord blood parasitaemia (RR 0.27, 95% CI 0.04 to 1.64; 2696 participants, 5 trials; very low-certainty evidence). Daily cotrimoxazole prophylaxis plus another drug regimen probably results in little or no difference in foetal loss (RR 1.03, 95% CI 0.73 to 1.46; 2957 participants, 5 trials; moderate-certainty evidence), and may result in little or no difference in neonatal mortality (RR 1.21, 95% CI 0.68 to 2.14; 2706 participants, 4 trials; low-certainty evidence). Due to the probability of an increased risk of mother-to-child HIV transmission and some adverse drug effects noted with mefloquine, we also looked at the results for dihydroartemisinin/piperaquine specifically. Dihydroartemisinin/piperaquine plus daily contrimoxazole probably results in little to no difference in maternal peripheral parasitaemia (RR 0.59, 95% CI 0.31 to 1.11; 1517 participants, 3 trials; moderate-certainty evidence) or anaemia at delivery (RR 0.95, 95% CI 0.82 to 1.10; 1454 participants, 2 trials; moderate-certainty evidence), but leads to fewer women having placental malaria when measured by histopathologic analysis (RR 0.67, 95% CI 0.50 to 0.90; 1570 participants, 3 trials; high-certainty evidence). The addition of dihydroartemisinin/piperaquine to daily cotrimoxazole probably made little to no difference to rates of low birth weight (RR 1.13, 95% CI 0.87 to 1.48; 1695 participants, 3 trials), foetal loss (RR 1.14, 95% CI 0.68 to 1.90; 1610 participants, 3 trials), or neonatal mortality (RR 1.03, 95% CI 0.39 to 2.72; 1467 participants, 2 trials) (all moderate-certainty evidence). We found low-certainty evidence of no increased risk of gastrointestinal drug-related adverse events (RR 1.42, 95% CI 0.51 to 3.98; 1447 participants, 2 trials) or mother-to-child HIV transmission (RR 1.54, 95% CI 0.26 to 9.19; 1063 participants, 2 trials). AUTHORS' CONCLUSIONS: Dihydroartemisinin/piperaquine and mefloquine added to daily cotrimoxazole seem to be efficacious in preventing malaria infection in HIV-positive pregnant women compared to daily cotrimoxazole alone. However, increased risk of HIV transmission to the foetus and poor drug tolerability may be barriers to implementation of mefloquine in practice. In contrast, the evidence suggests that dihydroartemisinin/piperaquine does not increase the risk of HIV mother-to-child transmission and is well tolerated.

Long-lasting insecticidal nets use and the prevalence of Plasmodium falciparum infection among pregnant women attending antenatal care at the Bonassama District Hospital, Littoral Region of Cameroon: a cross-sectional study.

BACKGROUND: Malaria during pregnancy continues to be a significant cause of morbidity and mortality for both infants and mothers, particularly in sub-Saharan African (SSA) countries, despite increased efforts to control it. The utilization of long-lasting insecticide-treated nets (LLINs) during pregnancy is a well-established strategy to reduce the prevalence of malaria. Nonetheless, inadequate adherence remains a persistent challenge in certain regions with high malaria endemicity. This research aimed to assess the effectiveness of long-lasting insecticidal nets in preventing asymptomatic malaria infections among pregnant women attending antenatal care at the Bonassama District Hospital in the Littoral Region of Cameroon. METHODS: A hospital-based cross-sectional study was conducted from March to June 2022. Data on sociodemographic characteristics and LLIN usage were collected through a structured questionnaire, while asymptomatic malaria infections were identified using a PfHRP2/pLDH malaria qualitative rapid diagnostic kit. The relationship between categorical variables was analyzed using the chi-square test and logistic regression at a significance level of 5%. RESULTS: Out of the 411 pregnant women included in the study, 35.4% were diagnosed with malaria. The LLIN utilization rate was 65.1%. The risk of malaria infection was 2.7 times higher (AOR = 2.75, 95% CI = 1.83-4.14, p < 0.001) among women who did not consistently use LLINs compared to those who did. Pregnant women in their first trimester (AOR = 3.40, 95% CI = 1.24-4.64, p = 0.010) and second trimester (AOR = 1.90, 95%CI = 0.99-3.62, p = 0.055) were more likely to sleep under net when compared to those in the third trimester. Younger women 20-29 years (71.4%), those in the first trimester (69.6%) and those who had the nets before pregnancy (68.9%) were amongst those who frequently used use the nets. Among the reasons reported for not frequently using LLINs were heat (55.2%), suffocation (13.6%) and the smell of nets (8.4%). CONCLUSION: The use of LLIN was moderately high among the participants in this study, though still below national target. Age group, religion and gestation period were the major factors determining the use of LLINs. Considering the proven effectiveness of LLINs in reducing malaria morbidity and mortality, it is imperative for the National Malaria Control Programme (NMCP) to remain focused in promoting both LLIN ownership and utilization to achieve the national target of 100% and 80%, respectively.