Neuroserpin, IL-33 and IL-17A as potential markers of mild symptoms of depressive syndrome in Toxoplasma gondii-infected pregnant women.

Introduction: Depressive syndrome (DS) is a common complication during pregnancy and the postpartum period, and is triggered by multiple organic/genetic and environmental factors. Clinical and biochemical follow-up is essential for the early diagnosis and prognosis of DS. The protozoan Toxoplasma gondii causes infectious damage to the fetus during parasite primary-infection. However, in long-term infections, pregnant women develop immune protection to protect the fetus, although they remain susceptible to pathological or inflammatory effects induced by T. gondii. This study aimed to investigate plasma inflammatory biomarkers in pregnant women seropositive and seronegative for T. gondii, with diagnoses of minor and moderate/severe DS. Methods: Pregnant women (n=45; age=18-39 years) were recruited during prenatal care at health centers in Ouro Preto, Minas Gerais, Brazil. Participants were asked to complete a socio-demographic questionnaire to be submitted to well-standardized DS scale calculators (Beck Depression Inventory Questionnaire, Edinburgh Postnatal Depression Scale, and Major Depressive Episode Module). Additionally, 4 mL of blood was collected for plasma neuroserpin, CCL2, IL-17A, and IL-33 analysis. Results: Pregnant volunteers with chronic T. gondii contact were all IgG+ (44%; n=21) and exhibited increased plasma IL-33, IL-17A, and neuroserpin levels, but not CCL2, compared to uninfected pregnant women. Using Beck's depression inventory, we observed an increase in plasma IL-17A and IL-33 in women with T. gondii infeCction diagnosed with mild DS, whereas neuroserpin was associated with minor and moderate/severe DS. Discussion: Our data suggest a close relationship between DS in pregnant women with chronic T. gondii infection and neurological conditions, which may be partially mediated by plasma neuroserpin, IL-33, and IL-17A levels.

Acute necrotising pancreatitis from ascariasis in a gravid patient.

Rarer causes of acute pancreatitis may be considered in certain settings, such as parasitism in endemic regions. This report describes a pregnant female (second trimester) in her 20s who presented with 3-day steady epigastric pain radiating to the back and passage of worm from the mouth. She was diagnosed with mild acute pancreatitis, given a significantly elevated serum lipase and absence of organ failures. Fecalysis showed Ascaris lumbricoides ova; hence, she was treated with mebendazole. Plain MR cholangiopancreatography showed an 842 mL necrotic pancreatic fluid collection and tubular flow void foci within the gallbladder and duodenum consistent with helminthiasis. The patient was managed conservatively in the absence of indications for drainage. The abdominal pain remarkably improved, and she underwent eventual vacuum-assisted delivery to a healthy term baby 4 months after the bout of acute pancreatitis.

Employing digital PCR for enhanced detection of perinatal Toxoplasma gondii infection: A cross-sectional surveillance and maternal-infant outcomes study in El Salvador.

Toxoplasma gondii is a parasitic infection that can be transmitted in utero, resulting in fetal chorioretinitis and other long-term neurological outcomes. If diagnosed early, pregnancy-safe chemotherapeutics can prevent vertical transmission. Unfortunately, diagnosis of acute, primary infection among pregnant women remains neglected, particularly in low-and-middle-income countries. Clinically actionable diagnosis is complex due to the commonality of infection during childhood and early adulthood which spawn long-last antibody titers and historically unreliable direct molecular diagnostics. The current study employed a cross-sectional T. gondii perinatal surveillance study using digital PCR, a next generation molecular diagnostic platform, and a maternal-fetal outcomes survey to ascertain the risk of vertical toxoplasmosis transmission in the Western Region of El Salvador. Of 198 enrolled mothers at the time of childbirth, 6.6% had evidence of recent T. gondii infection-85% of these cases were identified using digital PCR. Neonates born to these acutely infected mothers were significantly more likely to meconium aspiration syndrome and mothers were more likely to experience labor and delivery complications. Multivariable logistic regression found higher maternal T. gondii infection odds were associated with the presence of pet cats, the definitive T. gondii host. In closing, this study provides evidence of maternal T. gondii infection, vertical transmission and deleterious fetal outcomes in a vulnerable population near the El Salvador-Guatemala border. Further, this is the first published study to show clinical utility potential of digital PCR for accurate diagnosis of congenital toxoplasmosis cases.

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%).

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.

Considerations in the management of ocular toxoplasmosis in pregnancy: a review of literature.

Ocular toxoplasmosis is the most common cause of infectious posterior uveitis. Available literature is still conflicting regarding the incidence of recurrence during pregnancy as various calculations were employed in the different published studies. Although earlier reports have suggested a difference in presentation and an increase in severity during pregnancy, newer studies appear to show otherwise. Further diagnostic testing, including serologic and intraocular fluid sampling, may be indicated to increase the diagnostic accuracy in this special population of patients. The management of ocular toxoplasmosis during pregnancy is challenging as the foetus is additionally considered in the choice of treatment. Traditionally preferred anti-toxoplasmosis regimens containing antifolate drugs, such as pyrimethamine and trimethoprim-sulfamethoxazole, cannot be used routinely in pregnant patients, especially during the first trimester. This review includes literature on alternative treatments for ocular toxoplasmosis during pregnancy, including spiramycin and intravitreal treatment options.

Effectiveness of Intermittent Screening and Treatment of Malaria in Pregnancy on Maternal and Birth Outcomes in Selected Districts in Rwanda: A Cluster Randomized Controlled Trial.

BACKGROUND: Malaria during pregnancy can cause serious consequences including maternal anemia and low birthweight (LBW). Routine antenatal care (ANC) in Rwanda includes malaria symptom screening at each ANC visit. This cluster randomized controlled trial investigated whether adding intermittent screening with a malaria rapid diagnostic test at each routine ANC visit and treatment of positives during pregnancy (ISTp) is more effective than routine ANC for reducing malaria prevalence at delivery. METHODS: Between September 2016 and June 2018, pregnant women initiating ANC at 14 health centers in Rwanda were enrolled into ISTp or control arms. All women received an insecticide-treated bed net at enrollment. Hemoglobin concentration, placental and peripheral parasitemia, newborn outcome, birthweight, and prematurity were assessed at delivery. RESULTS: Nine hundred seventy-five women were enrolled in ISTp and 811 in the control group. Routine ANC plus ISTp did not significantly reduce polymerase chain reaction-confirmed placental malaria compared to control (adjusted relative risk [aRR], 0.94 [95% confidence interval {CI}, .59-1.50]; P = .799). ISTp had no impact on anemia (aRR, 1.08 [95% CI, .57-2.04]; P = .821). The mean birthweight of singleton newborns was not significantly different between arms (3054 g vs 3096 g, P = .395); however, women in the ISTp arm had a higher proportion of LBW (aRR, 1.59 [95% CI, 1.02-2.49]; P = .042). CONCLUSIONS: This is the only study to compare ISTp to symptomatic screening at ANC in a setting where intermittent preventive treatment is not routinely provided. ISTp did not reduce the prevalence of malaria or anemia at delivery and was associated with an increased risk of LBW. CLINICAL TRIALS REGISTRATION: NCT03508349.

Prevalence of asymptomatic malaria and associated factors among pregnant women at Boset District in East Shoa Zone, Oromia Region, Ethiopia: a cross-sectional study.

BACKGROUND: Malaria infection during pregnancy is a significant public health problem that puts pregnant women at risk. Interruption of transmission of asymptomatic malaria among a population remained a challenge and the host serves as a reservoir for the malaria parasite; and is also recognized as a major barrier to malaria elimination. This study aimed to assess the prevalence of asymptomatic malaria and associated factors among pregnant women in the Boset District, East Shoa Zone, Oromia, Ethiopia. METHODS: A community-based cross-sectional study was conducted to assess the prevalence of asymptomatic malaria and associated factors in pregnant women from February to March 2022. Using multistage sample techniques, 328 asymptomatic pregnant women were enrolled. Data were collected using a structured questionnaire. A rapid test and Giemsa-stained blood smear microscopy were used to diagnose Plasmodium infections. Epi info version 7 was used to code, enter, and clean data before being uploaded to SPSS version 25.0 for analysis. Bivariable and multivariable binary logistic regression were employed to find the associated factors. Variables in the multivariable model with a p-value < 0.05 were considered significantly associated with asymptomatic malaria. RESULTS: Of the total 328 pregnant women who participated in this study, 9(2.74%) and 10(3.05%) were confirmed to be infected with Plasmodium species by microscopy and rapid diagnostic tests, respectively. Asymptomatic malaria during pregnancy was found to be significantly associated with not using an insecticide-treated bed net [(P = 0.002, AOR: 9.61; 95% CI (2.22-41.53)], lack of consultation and health education about malaria prevention during Antenatal care attendance [(P = 0.04, AOR: 4.05; 95% CI (1.02, 16.05)], and living close stagnant water [(P = 0.02, AOR: 4.43; 95% CI (1.17,16.82)]. CONCLUSIONS: The current study showed that asymptomatic malaria is prevalent in pregnant women. Not using insecticide-treated bed nets, inadequate health education during antenatal care, and living close to stagnant water are significantly associated with malaria infection. Thus, using insecticide-treated bed nets, health education, and avoiding stagnant water from residential areas could play significant roles in preventing asymptomatic malaria among pregnant women in the study area.

Retrospective Evaluation of Toxoplasma Serology in Patients Admitted to a Training and Research Hospital Between 2017-2021

Objective: In this study, it was aimed to retrospectively evaluate the anti-Toxoplasma IgG, IgM and avidity index results of patients who were requested for Toxoplasma serology in our hospital between 01.01.2017 and 31.12.2021. Methods: Anti-Toxoplasma antibodies are studied with Abbott Architect I2000 SR device that using the chemiluminescent microparticle immunoassay method (CMIA), according to the company's recommendations. The age, gender, nationality, sending clinic/polyclinic, and pregnancy status information of patients were scanned from the hospital system. Results: In the five-year period between 2017 and 2021, 29.58% of anti-Toxoplasma IgG tests requested from 12694 patients and 0.94% of anti-Toxoplasma IgM tests sent from 12546 patients were found positive. It is striking that the number of test requests is higher in women. IgG positivity is highest in women in the age group of 30-39 (9.97%), and in men in the age group of 60-69 (6.97%). IgM positivity is higher in both women and men in the 20-29 age group (0.48% and 0.38%, respectively). Anti-Toxoplasma IgG was positive in 27.78% and IgM in 0.64% of the pregnant women. IgG positivity in Turkish and Syrian pregnant women were determined as 25.88%; 47.10% and IgM positivity as 0.49% and 1.83%, respectively, and the difference was statistically significant (p<0.001). Conclusion: Our anti-Toxoplasma antibody positivity was found to be compatible with studies conducted in different centers in our country. The fact that IgM positivity in women is high in the 20-29 age group, which is the childbearing age, emphasizes the importance of screening before and during pregnancy. Consistent with other studies in the literature, the rate of seropositivity in Syrian pregnant women was found to be higher than Turkish. This is important in terms of showing the effect of socio-cultural behaviors on prevalence.

Revisión sistemática de la exactitud diagnóstica de la gota gruesa en comparación con la reacción en cadena de la polimerasa para malaria asociada al embarazo, 2010-2022 / Systematic review of the diagnostic accuracy of thick smear compared to polymerase chain reaction for pregnancy-associated malaria, 2010-2022

RESUMEN Objetivos. Evaluar la exactitud de gota gruesa (GG) frente a la reacción en cadena de la polimerasa (PCR) cuantitativa para la malaria asociada al embarazo (MAE). Materiales y métodos. Se realizó una revisión sistemática de pruebas diagnósticas en nueve bases de datos. Se evaluó la calidad metodológica con QUADAS. Se estimó sensibilidad, especificidad, cociente de probabilidad positivo (CPP) y negativo (CPN), razón de odds diagnóstica (ORD) y área bajo la curva ROC. Se determinó la heterogeneidad con el estadístico Q de Der Simonian-Laird y la incertidumbre con el porcentaje de peso de cada estudio sobre el resultado global. Resultados. Se incluyeron diez estudios con 5691 gestantes, 1415 placentas y 84 neonatos. En los estudios con nPCR (PCR anidada) y qPCR (PCR cuantitativa) como estándar, los resultados de exactitud diagnóstica fueron estadísticamente similares, con sensibilidad muy baja (50 y 54%, respectivamente), alta especificidad (99% en ambos casos), alto CPP y deficiente CPN. Usando nPCR la OR diagnóstica fue 162 (IC95%=66-401) y el área bajo la curva ROC fue 95%, mientras que con qPCR fueron 231 (IC95%=27-1951) y 78%, respectivamente. Conclusiones. Mediante un protocolo exhaustivo se demostró el bajo desarrollo de investigaciones sobre la exactitud diagnóstica de la GG en MAE. Se demostró que la microscopía tiene un desempeño deficiente para el diagnóstico de infecciones asintomáticas o de baja parasitemia, lo que afianza la importancia de implementar otro tipo de técnicas en el seguimiento y control de las infecciones por malaria en las gestantes, con el fin de lograr el control y posible eliminación de la MAE.

ABSTRACT Objective. To evaluate the accuracy of thick smear (TS) versus quantitative polymerase chain reaction (PCR) for pregnancy-associated malaria (PAM). Materials and methods. We carried out a systematic review of diagnostic tests in nine databases. Methodological quality was evaluated with QUADAS. Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the ROC curve were estimated. Heterogeneity was determined with the Der Simonian-Laird Q method and uncertainty with the weighted percentage of each study on the overall result. Results. We included 10 studies with 5691 pregnant women, 1415 placentas and 84 neonates. In the studies with nested PCR (nPCR) and quantitative PCR (qPCR) as the standard, the diagnostic accuracy results were statistically similar, with very low sensitivity (50 and 54%, respectively), high specificity (99% in both cases), high PLR and poor NLR. When nPCR was used, the DOR was 162 (95%CI=66-401) and the area under the ROC curve was 95%, while with qPCR it was 231 (95%CI=27-1951) and 78%, respectively. Conclusions. We demonstrated that research on the diagnostic accuracy of TS in PAM is limited. Microscopy showed poor performance in the diagnosis of asymptomatic or low parasitemia infections, which reinforces the importance of implementing other types of techniques for the follow-up and control of malaria infections in pregnant women, in order to achieve the control and possible elimination of PAM.

Active case detection and treatment of malaria in pregnancy using LAMP technology (LAMPREG): a pragmatic randomised diagnostic outcomes trial-study protocol.

INTRODUCTION: Malaria is one of the major public health problems in sub-Saharan Africa. It contributes significantly to maternal and fetal morbidity and mortality in affected countries. This study aims to evaluate the impact of enhanced case detection using molecular testing called loop-mediated isothermal amplification (LAMP) on birth outcomes in a prospective study design. METHODS AND ANALYSIS: A pragmatic randomised diagnostic outcomes trial will be conducted in several health institutes in different Ethiopian regions. Women (n=2583) in their first and second trimesters of pregnancy will be included in the study and individually randomised to the standard of care or enhanced case detection arms, and followed until delivery. Enrolment will encompass the malaria peak transmission seasons. In the standard of care arm, a venous blood sample will be collected for malaria diagnosis only in symptomatic patients. In contrast, in the intervention arm, mothers will be tested by a commercially available Conformité Européene (CE)-approved LAMP malaria test, microscopy and rapid diagnostic test for malaria regardless of their symptoms at each antenatal care visit. The primary outcome of the study is to measure birth weight. ETHICS AND DISSEMINATION: The study was approved by the following ethical research boards: Armauer Hansen Research Institute/ALERT Ethics Review Committee (FORM AF-10-015.1, Protocol number PO/05/20), the Ethiopia Ministry of Science and Higher Education National Research Ethics Review Committee (approval SRA/11.7/7115/20), the Ethiopia Food and Drug Administration (approval 02/25/33/I), UCalgary Conjoint Health Research Ethics Board (REB21-0234). The study results will be shared with the institutions and stakeholders such as the Ethiopia Ministry of Health, the Foundation for Innovative Diagnostics, WHO's Multilateral initiative on Malaria - Tropical Diseases Research (TDR-MIM), Roll Back Malaria and the Malaria in Pregnancy Consortium. The study results will also be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT03754322.

Toxoplasma gondii outbreak in southern Brazil: heterogeneity of the serological humoral response in pregnant women and outcomes in newborns.

The aim of the study was to describe the heterogeneity of the humoral immune response and pregnancy outcomes in infected women during an outbreak of toxoplasmosis. Forty-two pregnant women referred to the University Hospital of Santa Maria (HUSM), RS, Brazil in 2018 and 2019, were evaluated. Clinical symptoms were reported in 33.3% of the patients. The majority (64.3%) of symptomatic pregnant women had anti T. gondii IgM antibodies index >7.0. Considering asymptomatic pregnant women, 46.4% presented antibodies IgM index below 3.0. Anti T. gondii IgG low avidity antibodies are present in 23.5% of pregnant women with a IgM index <3.0. Three newborns had the congenital form of the infection, and of these, only 1 had a positive IgM result. The serological response detected at the time of diagnosis of the infection is heterogeneous, which can make it difficult to interpret the tests, due to the presence of non-classical serological profiles.

Diagnosis of Congenital Toxoplasmosis: Performance of Four IgG and IgM Automated Assays at Birth in a Tricentric Evaluation.

For postnatal diagnosis of congenital toxoplasmosis (CT), the gold standard for the detection of anti-Toxoplasma IgM in newborns relies on the immunosorbent agglutination assay (ISAGA), which is manufactured from whole Toxoplasma parasites that become difficult to maintain. For IgG, only the Platelia assay provides a validated assay for cord blood according to the manufacturer, allowing its use in this context. We compared the analytical performance of four commercialized automated assays, Platelia, Abbott, Vidas, and Liaison, for the detection of IgG and IgM in the cord blood or peripheral blood of newborns from women infected during pregnancy. The assays were performed on samples from 509 newborns, collected from the university hospitals of Montpellier, Nîmes, and Toulouse. For IgM, the four assays appeared to be sufficiently informative to be used for congenital toxoplasmosis diagnosis (area under the curve [AUC] > 0.8, receiver operating characteristic [ROC] analysis), with Platelia showing the best performance, similar to ISAGA with regard to accuracy (83%). For the Vidas (76%), Abbott (75%), and Liaison (74%) assays, the accuracy was significantly lower. Maternal treatment significantly decreased the sensitivity of all the assays. For IgG, the four evaluated assays showed a sensitivity of over 90%, with Abbott (95%) and Liaison (94%), exhibiting a significantly higher sensitivity than Platelia (90%). Furthermore, Abbott showed its superiority in the cases of maternal infection during the third trimester. In the context of the newborns of mothers infected by Toxoplasma gondii during pregnancy, to ensure efficient care, Platelia and Abbott seemed to be the most suitable reference tests for the detection of IgM for the former and IgG for the latter.

The Angiopoietin-Tie2 axis contributes to placental vascular disruption and adverse birth outcomes in malaria in pregnancy.

BACKGROUND: Malaria during pregnancy is a major contributor to the global burden of adverse birth outcomes including fetal growth restriction, preterm birth, and fetal loss. Recent evidence supports a role for angiogenic dysregulation and perturbations to placental vascular development in the pathobiology of malaria in pregnancy. The Angiopoietin-Tie2 axis is critical for placental vascularization and remodeling. We hypothesized that disruption of this pathway would contribute to malaria-induced adverse birth outcomes. METHODS: Using samples from a previously conducted prospective cohort study of pregnant women in Malawi, we measured circulating levels of angiopoietin-1 (Angpt-1) and Angpt-2 by Luminex (n=1392). We used a preclinical model of malaria in pregnancy (Plasmodium berghei ANKA [PbA] in pregnant BALB/c mice), genetic disruption of Angpt-1 (Angpt1+/- mice), and micro-CT analysis of placental vasculature to test the hypothesis that disruptions to the Angpt-Tie2 axis by malaria during pregnancy would result in aberrant placental vasculature and adverse birth outcomes. FINDINGS: Decreased circulating levels of Angpt-1 and an increased ratio of Angpt-2/Angpt-1 across pregnancy were associated with malaria in pregnancy. In the preclinical model, PbA infection recapitulated disruptions to the Angiopoietin-Tie2 axis resulting in reduced fetal growth and viability. Malaria decreased placental Angpt-1 and Tie2 expression and acted synergistically with reduced Angpt-1 in heterozygous dams (Angpt1+/-), to worsen birth outcomes by impeding vascular remodeling required for placental function. INTERPRETATION: Collectively, these data support a mechanistic role for the Angpt-Tie2 axis in malaria in pregnancy, including a potential protective role for Angpt-1 in mitigating infection-associated adverse birth outcomes. FUNDING: This work was supported by the Canadian Institutes of Health Research (CIHR), Canada Research Chair, and Toronto General Research Institute Postdoctoral Fellowship Award. The parent trial was supported by the European & Developing Countries Clinical Trials Partnership and the Malaria in Pregnancy Consortium, which was funded by the Bill & Melinda Gates Foundation. The funders had no role in design, analysis, or reporting of these studies.

Safety and efficacy of intermittent presumptive treatment with sulfadoxine-pyrimethamine using rapid diagnostic test screening and treatment with dihydroartemisinin-piperaquine at the first antenatal care visit (IPTp-SP+): study protocol for a randomized controlled trial.

BACKGROUND: Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by the World Health Organization for the prevention of malaria in pregnancy (MIP)-associated adverse outcomes in high burden areas. However, the efficacy of IPTp-SP has decreased in step with increasing parasite drug resistance. Suitable alternative strategies are needed. METHODS: This is a protocol for a phase IIIb open-label, two-armed randomized controlled superiority trial to assess the safety and efficacy of a hybrid approach to IPTp combining screening and treatment with dihydroartemisinin-piperaquine (DP) to the current IPTp-SP regimen at the first antenatal care clinic visit. Pregnant women without HIV infection and without signs or symptoms of malaria will be randomized to either standard IPTp-SP or hybrid IPTp-SP plus screening and treatment (IPTp-SP+). In the IPTp-SP+ arm, participants who screen positive by rapid diagnostic test for P. falciparum will be treated with DP at the first antenatal visit while those who screen negative will receive SP per current guidelines. All participants will be administered SP on days 35 and 63 and will be actively followed biweekly up to day 63 and then monthly until delivery. Infants will be followed until 1 year after delivery. The primary endpoint is incident PCR-confirmed MIP at day 42. Secondary endpoints include incident MIP at other time points, placental malaria, congenital malaria, hemoglobin trends, birth outcomes, and incidence of adverse events in infants up to the first birthday. DISCUSSION: A hybrid approach to IPTp that combines screening and treatment with an artemisinin-based combination therapy at the first visit with standard IPTp-SP is hypothesized to confer added benefit over IPTp-SP alone in a high malaria transmission area with prevalent SP resistant parasites. TRIAL REGISTRATION: Pan African Clinical Trials Registry 201905721140808 . Registered retrospectively on 11 May 2019.

IgG Subclasses and Congenital Transmission of Chagas Disease.

The mechanism of vertical transmission of Trypanosoma cruzi is poorly understood. In this study, we evaluated the role of IgG subclasses in the congenital transmission of Chagas disease. We conducted a case-control study in a public maternity hospital in Santa Cruz, Bolivia, enrolling women at delivery. Thirty women who transmitted T. cruzi to their newborns (cases), and 51 women who did not (controls) were randomly selected from 676 total seropositive women. Trypanosoma cruzi-specific IgG1, IgG2, and IgG3 levels were measured by in-house ELISA. The IgG4 levels were unmeasurable as a result of low levels in all participants. Quantitative polymerase chain reaction results and demographic factors were also analyzed. One-unit increases in normalized absorbance ratio of IgG1 or IgG2 levels increased the odds of congenital T. cruzi transmission in Chagas-seropositive women by 2.0 (95% CI: 1.1-3.6) and 2.27 (95% CI: 0.9-5.7), adjusted for age and previous blood transfusion. Odds of congenital transmission were 7.0 times higher in parasitemic mothers (95% CI: 2.3-21.3, P < 0.01) compared with nonparasitemic mothers. We observed that all mothers with IgG1 ≥ 4 were transmitters (sensitivity = 20%, specificity = 100%). Additionally, no mothers with IgG2 < 1.13 were transmitters (sensitivity = 100%, specificity = 21.6%). We demonstrated that IgG subclasses and parasite presence in blood are associated with vertical transmission of T. cruzi and could identify women at increased risk for congenital transmission by measuring IgG subclasses. These measures have potential as objective screening tests to predict the congenital transmission of Chagas.

Acute Toxoplasmosis During Pregnancy: A Hard Call

Toxoplasma gondii is an obligate intracellular parasite that infects all animals, including humans, and causes toxoplasmosis. If toxoplasmosis occurs during pregnancy, it may affect the foetus owing to transplacental transmission. Such transmission may lead to foetal complications, some of which can be very serious, e.g. hydrocephaly and chorioretinitis; however, not all cases of acute toxoplasmosis during pregnancy result in foetal complications. The decision whether to continue or terminate the pregnancy is a difficult problem for families as well as healthcare professionals, thus making it important. Here we present a case of acute toxoplasmosis at 6 weeks of pregnancy. The patient was directly advised to terminate the pregnancy. However, with detailed laboratory analyses, close follow-up and treatment to prevent transplacental transmission, she successfully completed the pregnancy and eventually delivered a healthy baby. By presenting this case, we aimed to review acute toxoplasmosis during pregnancy.

Meta-analysis of the prevalence of malaria associated with pregnancy in Colombia 2000-2020.

Knowledge about malaria associated with pregnancy is scarce in Latin America, and in Colombia, little is known about the magnitude of this infection. A systematic review was conducted to determine the prevalence of malaria associated with pregnancy (MAP) and each of its three forms: gestational (GM), placental (PM), and congenital (CM) tested using thick blood smear (TBS) and PCR. Also to compare the proportion of cases due to Plasmodium falciparum and Plasmodium vivax in Colombia from the year 2000-2020. We searched in Pubmed, Science Direct, EMBASE, EMCare, Cochrane Library, Scielo, Lilacs, Google Scholar, libraries, and repositories of Colombian universities, to obtain data on prevalence of GM, PM and CM with their respective testing method. We performed a meta-analysis with a random-effects model to obtain pooled prevalence of MAP and its three forms categorized by testing methods (TBS and PCR). We used data from 14 studies (out of 258 screened) contributing 7932, 2506 women for GM and PM respectively, also data on 1143 umbilical cord blood samples, and 899 peripheral blood of neonates. We found prevalence by TBS as, MAP 4.5% (95%CI = 2.9-6.9), GM 5.8% (95%CI = 3.8-8.7), PM 3.4% (95%CI = 1.7-6.7) and CM 1.3% (95%CI = 0.6-3.0). With PCR the prevalence was, MAP 14.4% (95%CI = 7.6-25.5), GM 16.7% (95%CI = 9.0-28.8), PM 11.0% (95%CI = 4.1-26.3) and CM 16.2% (95%CI = 8.2-29.5). The prevalence of submicroscopic infection was 8.5% (95%CI = 3.4-19.7) in GM, 10.1% (95%CI = 3.5-25.5) in PM and 22.0% (95%CI = 13.2-34.3) in CM. Infections by P. vivax was dominant over P. falciparum when tested with TBS, the PCR test gave similar proportions of P. falciparum and P. vivax. This meta-analysis has demonstrated high prevalence of MAP in Colombia, and highlights the urgent need to increase attention of researchers, research funding institutions, government agencies, and health authorities to study and intervene MAP, that has currently been under investigated.

Detection and genetic characterisation of Toxoplasma gondii circulating in free-range chickens, pigs and seropositive pregnant women in Benue state, Nigeria.

Toxoplasma gondii parasites present strong but geographically varied signatures of population structure. Populations sampled from Europe and North America have commonly been defined by over-representation of a small number of clonal types, in contrast to greater diversity in South America. The occurrence and extent of genetic diversity in African T. gondii populations remains understudied, undermining assessments of risk and transmission. The present study was designed to establish the occurrence, genotype and phylogeny of T. gondii in meat samples collected from livestock produced for human consumption (free-range chickens, n = 173; pigs, n = 211), comparing with T. gondii detected in blood samples collected from seropositive pregnant women (n = 91) in Benue state, Nigeria. The presence of T. gondii DNA was determined using a published nested polymerase chain reaction, targeting the 529 bp multicopy gene element. Samples with the highest parasite load (assessed using quantitative PCR) were selected for PCR-restriction fragment length polymorphism (PCR-RFLP) targeting the surface antigen 3 (SAG3), SAG2 (5' and 3'), beta-tubulin (BTUB) and dense granule protein 6 (GRA6) loci, and the apicoplast genome (Apico). Toxoplasma gondii DNA was detected in all three of the populations sampled, presenting 30.6, 31.3 and 25.3% occurrence in free-range chickens, pigs and seropositive pregnant women, respectively. Quantitative-PCR indicated low parasite occurrence in most positive samples, limiting some further molecular analyses. PCR-RFLP results suggested that T. gondii circulating in the sampled populations presented with a type II genetic background, although all included a hybrid type I/II or II/III haplotype. Concatenation of aligned RFLP amplicon sequences revealed limited diversity with nine haplotypes and little indication of host species-specific or spatially distributed sub-populations. Samples collected from humans shared haplotypes with free-range chickens and/or pigs. Africa remains under-explored for T. gondii genetic diversity and this study provides the first detailed definition of haplotypes circulating in human and animal populations in Nigeria.