Association between lymphadenopathy after toxoplasmosis seroconversion in pregnancy and risk of congenital infection.

The aim of the study was to describe the pregnancy outcome of a large cohort of women with toxoplasmosis seroconversion in pregnancy and to investigate the relation between maternal lymphadenopathy and risk of congenital toxoplasmosis (CT). This was a retrospective study involving women with confirmed toxoplasmosis seroconversion in pregnancy between 2001 and 2017. Women were clinically evaluated for lymphadenopathy and classified as follows: lymphadenopathy absent (L-) or lymphadenopathy present (L+). The mothers were treated and followed-up according to local protocol, and neonates were monitored at least for 1 year in order to diagnose CT. A total of 218 women (one twin pregnancy) were included in the analysis. Pregnancy outcome was as follows: 149 (68%) of children not infected, 62 (28.3%) infected, 4 (1.8%) first trimester termination of pregnancy, 2 (0.9%) first trimester miscarriages, and 3 (1.4%) stillbirths (of which one already counted in the infected cohort). 13.8% of women were L+ , and they were nearly three times more likely to have a child with CT compared to L- women (aOR, 2.90; 95%CI, 1.28-6.58). Moreover, the result was still statistically significant when the analysis was restricted to 81 children whose mothers were clinically examined and received treatment within 5 weeks from estimated time of infection. In conclusion, there is a positive association between L+ status in pregnant women, and risk of CT also confirmed when restricting the analysis to women with early diagnosis of seroconversion and treatment. This data could be very useful in counselling pregnant women with toxoplasmosis seroconversion and lead to direct a more specific therapeutic and diagnostic protocol.

Congenital Toxoplasmosis: Missed Opportunities for Diagnosis and Prevention.

OBJECTIVES: Identify missed opportunities for the prevention and early diagnosis of congenital toxoplasmosis (CT) in infants followed up in a reference center for pediatric infectious diseases (PID) in Rio de Janeiro between January 2007 and December 2016. METHODS: Descriptive study including infants with CT, diagnosis established based on Brazil's Ministry of Health's criteria. All data regarding the infants and their mother's prenatal care were collected from the medical records of the Instituto de Puericultura e Pediatria Martagão Gesteira (IPPMG)-a tertiary public pediatric university hospital. The study enrolled infants aged between 0 and 12 months followed up in the PID department of IPPMG and with confirmed infection by Toxoplasma gondii in the period between January 2007 and December 2016. All patients with diagnosis of CT registered in the PID database of the IPPMG and admitted in the above-mentioned period were included in the study. Patients whose records were not available, or who went to just one clinic appointment were excluded. RESULTS: The obstetric history of all 44 women, whose infants (45) were diagnosed with CT, was analyzed. Their median age was 22 years. None had undergone preconception serological testing for toxoplasmosis. Only 20 (45%) of them started antenatal care during the first trimester of gestation, a total of 24 (55%) had more than six antenatal care visits, and 16% of those did not undergo serological testing for toxoplasmosis. None were adequately informed of preventive measures. The diagnosis of acute toxoplasmosis was made in 50% of these pregnancies but 32% of the women were not treated. Only 10 children of these mothers were adequately screened and treated at birth. CONCLUSION: Despite the existence of national recommendations, several opportunities were missed to prevent CT during the antenatal period and to diagnose and treat this condition in the neonatal period.

The impact of gravidity, symptomatology and timing of infection on placental malaria.

BACKGROUND: Placental malaria is associated with increased risk of adverse perinatal outcomes. While primigravidity has been reported as a risk factor for placental malaria, little is known regarding the relationship between gravidity, symptomatology and timing of Plasmodium falciparum infection and the development of placental malaria. METHODS: The aim of this study was to investigate the relationship between the development of placental malaria and gravidity, timing of infection, and presence of symptoms. This is a secondary analysis of data from a double-blind randomized control trial of intermittent preventive therapy during pregnancy in Uganda. Women were enrolled from 12 to 20 weeks gestation and followed through delivery. Exposure to malaria parasites was defined as symptomatic (fever with positive blood smear) or asymptomatic (based on molecular detection of parasitaemia done routinely every 4 weeks). The primary outcome was placental malaria diagnosed by histopathology, placental blood smear, and/or placental blood loop-mediated isothermal amplification. Multivariate analyses were performed using logistic regression models. Subgroup analysis was performed based on the presence of symptomatic malaria, gravidity, and timing of infection. RESULTS: Of the 228 patients with documented maternal infection with malaria parasites during pregnancy, 101 (44.3%) had placental malaria. Primigravidity was strongly associated with placental malaria (aOR 8.90, 95% CI 4.34-18.2, p < 0.001), and each episode of malaria was associated with over a twofold increase in placental malaria (aOR 2.35, 95% CI 1.69-3.26, p < 0.001). Among multigravid women, the odds of placental malaria increased by 14% with each advancing week of gestation at first documented infection (aOR 1.14, 95% CI 1.02-1.27, p = 0.02). When stratified by the presence of symptoms, primigravidity was only associated with placental malaria in asymptomatic women, who had a 12-fold increase in the odds of placental malaria (aOR 12.19, 95% CI 5.23-28.43, p < 0.001). CONCLUSIONS: Total number of P. falciparum infections in pregnancy is a significant predictor of placental malaria. The importance of timing of infection on the development of placental malaria varies based on gravidity. In primigravidas, earlier asymptomatic infections were more frequently identified in those with placental malaria, whereas in multigravidas, parasitaemias detected later in gestation were associated with placental malaria. Earlier initiation of an effective intermittent preventive therapy may help to prevent placental malaria and improve birth outcomes, particularly in primigravid women.

Systematic review of statistical methods for safety data in malaria chemoprevention in pregnancy trials.

BACKGROUND: Drug safety assessments in clinical trials present unique analytical challenges. Some of these include adjusting for individual follow-up time, repeated measurements of multiple outcomes and missing data among others. Furthermore, pre-specifying appropriate analysis becomes difficult as some safety endpoints are unexpected. Although existing guidelines such as CONSORT encourage thorough reporting of adverse events (AEs) in clinical trials, they provide limited details for safety data analysis. The limited guidelines may influence suboptimal analysis by failing to account for some analysis challenges above. A typical example where such challenges exist are trials of anti-malarial drugs for malaria prevention during pregnancy. Lack of proper standardized evaluation of the safety of antimalarial drugs has limited the ability to draw conclusions about safety. Therefore, a systematic review was conducted to establish the current practice in statistical analysis for preventive antimalarial drug safety in pregnancy. METHODS: The search included five databases (PubMed, Embase, Scopus, Malaria in Pregnancy Library and Cochrane Central Register of Controlled Trials) to identify original English articles reporting Phase III randomized controlled trials (RCTs) on anti-malarial drugs for malaria prevention in pregnancy published from January 2010 to July 2019. RESULTS: Eighteen trials were included in this review that collected multiple longitudinal safety outcomes including AEs. Statistical analysis and reporting of the safety outcomes in all the trials used descriptive statistics; proportions/counts (n = 18, 100%) and mean/median (n = 2, 11.1%). Results presentation included tabular (n = 16, 88.9%) and text description (n = 2, 11.1%). Univariate inferential methods were reported in most trials (n = 16, 88.9%); including Chi square/Fisher's exact test (n = 12, 66.7%), t test (n = 2, 11.1%) and Mann-Whitney/Wilcoxon test (n = 1, 5.6%). Multivariable methods, including Poisson and negative binomial were reported in few trials (n = 3, 16.7%). Assessment of a potential link between missing efficacy data and safety outcomes was not reported in any of the trials that reported efficacy missing data (n = 7, 38.9%). CONCLUSION: The review demonstrated that statistical analysis of safety data in anti-malarial drugs for malarial chemoprevention in pregnancy RCTs is inadequate. The analyses insufficiently account for multiple safety outcomes potential dependence, follow-up time and informative missing data which can compromise anti-malarial drug safety evidence development, based on the available data.

Relationship between placenta malaria and mother to child transmission of HIV infection in pregnant women in South East Nigeria.

BACKGROUND: This study determined the rate of mother-to-child transmission (MTCT) of HIV among HIV positive women with placenta malaria and factors associated with placenta malaria. METHODS: This was a prospective observational study of booked HIV positive pregnant women in labour. A smear for malaria parasite was made from blood taken from the placental tissue post-delivery. The baby HIV testing was done with DNA polymerase chain reaction at 6 weeks postpartum. Data on age, parity, gestational age, religion, address, highest educational attainment and knowledge about malaria prevention in pregnancy was obtained with questionnaires and analysed using SPSS version 20. The P-value was set at 0.05 providing a confidence interval of 95%. RESULTS: A total of 174 booked HIV women participated in this study. The placental malaria parasitaemia prevalence was 44.8%. Overall rate of MTCT of HIV infection was 17.2%. Number of infants with HIV infection among women with maternal placental malarial parasitaemia was 30/78 (38.5%), while it was 0/96 (0%) for women without placenta malaria. There was significant relationship between placenta malaria density and infant HIV status (P-value = 0.001). The relative risk for MTCT of HIV for women with placenta malaria Density > 5000 was 25% with 95% confidence interval of 11.41-54.76%. CONCLUSION: The mother-to-child transmission rate of HIV was high among HIV positive women with placental malaria parasitaemia. There is the need to review the malarial treatment and prophylactic measures at least in this group of women and to establish the nature of relationship between placenta malaria and MTCT of HIV infection.

Factors associated with sub-microscopic placental malaria and its association with adverse pregnancy outcomes among HIV-negative women in Dar es Salaam, Tanzania: a cohort study.

BACKGROUND: Malaria infection during pregnancy has negative health consequences for both mothers and offspring. Sub-microscopic malaria infection during pregnancy is common in most African countries. We sought to identify factors associated with sub-microscopic placental malaria, and its association with adverse pregnancy outcomes among HIV-negative pregnant women in Dar es Salaam, Tanzania. METHODS: We recruited a cohort of pregnant women during their first trimester and assessed for the occurrence of placental malaria and pregnancy outcomes. The follow-up was done monthly from recruitment until delivery. Histopathology placental malaria positive results were defined as the presence of malaria pigment or parasitized erythrocytes on the slide (histology-positive (HP)), and the sub-microscopic placental infection was defined as positive Plasmodium falciparum DNA by polymerase chain reaction (DNA PCR) amplification in a negative histopathology test. Adverse pregnancy outcomes investigated included low birth weight (birth weight below 2.5 kg), prematurity (live birth below 37 weeks), and small-for-gestational-age (SGA) (live born with a birth weight below 10th percentile for gestational age and sex). Weighted baseline category logit, log-binomial, and log-Poisson models were used to assess factors associated with placental malaria, and its association with adverse pregnancy outcomes. RESULTS: Among 1115 women who had histopathology and DNA PCR performed, 93 (8%) had HP placental infection, and 136 (12%) had the sub-microscopic placental infection. The risk of sub-microscopic placental malaria was greater in women who did not use mosquito prevention methods such as bed nets, fumigation, or mosquito coils (odds ratio (OR) = 1.75; 95% confidence interval (CI): 1.05-2.92; P = 0.03) and in women who were anemic (OR = 1.59; 95% CI: 1.20-2.11; P = 0.001). Women who were underweight had reduced odds of sub-microscopic placental malaria infection (OR = 0.33; 95% CI: 0.17-0.62; P = 0.001). Women who were overweight/obese had 1.48 times higher the odds of HP placental malaria compared to normal weight (OR = 1.48; 95% CI: 1.03-2.11; P = 0.03). HP placental malaria infection was associated with an increased risk of SGA births (RR = 1.30, 95% CI: 0.98-1.72, P = 0.07). In contrast, the sub-microscopic infection was associated with a reduced risk of SGA births (RR = 0.61, 95% CI: 0.43-0.88, P = 0.01). Placental malaria was not associated with low birth weight or prematurity. CONCLUSION: Malaria prevention methods and maternal nutrition status during early pregnancy were important predictors of sub-microscopic placental malaria. More research is needed to understand sub-microscopic placental malaria and the possible mechanisms mediating the association between placental malaria and SGA.

An upstream open reading frame (uORF) signals for cellular localization of the virulence factor implicated in pregnancy associated malaria.

Plasmodium falciparum, the causative agent of the deadliest form of human malaria, alternates expression of variable antigens, encoded by members of a multi-copy gene family named var. In var2csa, the var gene implicated in pregnancy-associated malaria, translational repression is regulated by a unique upstream open reading frame (uORF) found only in its 5' UTR. Here, we report that this translated uORF significantly alters both transcription and posttranslational protein trafficking. The parasite can alter a protein's destination without any modifications to the protein itself, but instead by an element within the 5' UTR of the transcript. This uORF-dependent localization was confirmed by single molecule STORM imaging, followed by fusion of the uORF to a reporter gene which changes its cellular localization from cytoplasmic to ER-associated. These data point towards a novel regulatory role of uORF in protein trafficking, with important implications for the pathology of pregnancy-associated malaria.

Malaria in Pregnancy in Endemic Regions of Colombia: High Frequency of Asymptomatic and Peri-Urban Infections in Pregnant Women with Malaria.

Background: Malaria in pregnancy (MiP) has been associated with adverse pregnancy outcomes. There is limited information on MiP in low transmission regions as Colombia. This study aimed to describe the epidemiology of MiP through active surveillance of infections by microscopy and polymerase chain reaction (PCR). Methods: A cross-sectional study was conducted between May 2016 and January 2017 in five municipalities (Apartadó, Turbo, El Bagre, Quibdó, and Tumaco) in Colombia. Pregnant women self-presenting at health centers for antenatal care visits, seeking medical care for suspected malaria, or delivery, were enrolled. Diagnosis of Plasmodium spp was made in peripheral and placental blood samples by microscopy and PCR. Results: A total of 787 pregnant women were enrolled; plasmodial infection was diagnosed by microscopy in 4.2% (95% CI 2.8-5.6; 33/787) or by nPCR in 5.3% (95% CI 3.8-6.9; 42/787) in peripheral blood. Most of the infections were caused by P. falciparum (78.5%), and 46% were afebrile (asymptomatic). Women in the first and second trimester of pregnancy were more likely to be infected (aOR = 3.06, 95%CI = 1.6 - 5.8). To live in the urban/peri-urban area (aOR = 3.04, 95%CI = 1.4 - 6.56), to have a history of malaria during last year (aOR = 5.45, 95%IC = 2.16 - 13.75), and the infrequent bed net usage (aOR = 2.8, 95%CI = 1.31 - 5.97) were associated with the infection. Pregnant infected women had a higher risk of anaemia (aOR = 2.18, 95%CI = 1.15 - 4.12) and fever (aOR = 14.2, 95%CI = 6.89 - 29.8). Conclusion: The screening for malaria during antenatal care in endemic areas of Colombia is highly recommended due to the potential adverse effects of Plasmodium spp. infection in pregnancy and as an important activity for the surveillance of asymptomatic infections in the control of malaria.

Influence of Sexually Transmitted Infections in Pregnant Adolescents on Preterm Birth and Chorioamnionitis.

Background: Adolescents have an increased risk of preterm birth (PTB) and sexually transmitted infections (STIs). We examined the prevalence and impact of STIs (gonorrhea, chlamydia, and trichomonas) on PTB and chorioamnionitis in pregnant adolescents. Methods: This retrospective cohort study utilized the first pregnancy delivered at an urban hospital among patients ≤ 19 years old over a 5-year period. Poisson regression with robust standard errors was used to estimate prevalence ratios (PR) and 95% confidence intervals (CI) of the association between STIs and PTB (<37 weeks) and chorioamnionitis identified by clinical or placental pathology criteria. Results: 739 deliveries were included. 18.8% (n = 139) of births were preterm. The overall prevalence of STIs during pregnancy was 16.5% (Chlamydia trachomatis: 13.1%, n = 97; Trichomonas vaginalis: 3.7%, n = 27; and Neisseria gonorrheae: 3.1%, n = 23). Detection of C. trachomatis, T. vaginalis, or N. gonorrheae was not associated with increased PTB. While infection with N. gonorrheae and C. trachomatis did not increase the likelihood of any chorioamnionitis, infection with T. vaginalis significantly increased the likelihood of any chorioamnionitis diagnosis (aPR 2.19, 95% CI 1.26-3.83). Conclusion: In this adolescent population with a high rate of PTB, in whom most received appropriate STI treatment, we did not find an association between STI during pregnancy and an increased rate of PTB. However, an infection with T. vaginalis was associated with an increased likelihood of chorioamnionitis. Early detection of STIs may prevent adverse pregnancy outcomes. Continued vigilance in STI screening during pregnancy, including consideration of universal Trichomonas vaginalis screening, is merited in this high-risk population.

Impact of Microscopic and Submicroscopic Parasitemia During Pregnancy on Placental Malaria in a High-Transmission Setting in Uganda.

BACKGROUND: Placental malaria is a major cause of adverse birth outcomes. However, data are limited on the relationships between longitudinal measures of parasitemia during pregnancy and placental malaria. METHODS: Data came from 637 women enrolled in a randomized controlled trial of intermittent preventive treatment of malaria in pregnancy (IPTp) from Uganda. Plasmodium falciparum parasitemia was assessed using microscopy and ultrasensitive quantitative PCR at intervals of 28 days from 12 to 20 weeks gestation through delivery. Multivariate analysis was used to measure associations between characteristics of parasitemia during pregnancy and the risk of placental malaria based on histopathology. RESULTS: Overall risk of placental malaria was 44.6%. None of the 34 women without parasitemia detected during pregnancy had evidence of placental malaria. Increasing proportion of interval assessments with parasitemia and higher parasite densities were independently associated with an increased risk of placental malaria. Higher gravidity and more effective IPTp were associated with a decreased risk of placental malaria. Women with parasitemia only detected before the third trimester still had an increased risk of placental malaria. CONCLUSIONS: The frequency, density, and timing of parasitemia are all important risk factors for placental malaria. Interventions should target the prevention of all levels of parasitemia throughout pregnancy.

Alterations in Placental Gene Expression of Pregnant Women with Chronic Chagas Disease.

Trypanosoma cruzi infection in women of reproductive age is associated with congenital transmission and adverse pregnancy outcomes. The placenta is a key barrier to infection. Gene expression profiles of term placental environment from T. cruzi-seropositive (SP) and -seronegative (SN) mothers were characterized by RNA-Seq. Nine pools of placental RNA paired samples were used: three from SN and six from SP tissues. Each pool consisted of female/male newborns and vaginal/cesarean delivery binomials. No newborn was congenitally infected. T. cruzi satellite DNA quantitative PCR in placental tissues and maternal and neonatal blood, and parasite 18S quantitative RT-PCR from placental RNA were negative, except in three SP women's bloodstream. To identify pathways associated with maternal T. cruzi infection, a gene-set association analysis was implemented: SP placental samples showed overexpression of inflammatory response and lymphocytic activation, whereas numerous biosynthetic processes were down-regulated. About 42 genes showed a significant fold-change between SP and SN groups. KISS1 and CGB5 were down-regulated, whereas KIF12, HLA-G, PRG2, TAC3, FN1, and ATXN3L were up-regulated. Several expressed genes in SP placentas encode proteins associated with preeclampsia and miscarriage. This first transcriptomics study in human term placental environment shows a placental response that may affect the fetus while protecting it from parasite infection; this host response could be responsible for the low rate of congenital transmission in chronic Chagas disease.

Microscopic and submicroscopic Plasmodium falciparum infection, maternal anaemia and adverse pregnancy outcomes in Papua New Guinea: a cohort study.

BACKGROUND: Infection during pregnancy with Plasmodium falciparum is associated with maternal anaemia and adverse birth outcomes including low birth weight (LBW). Studies using polymerase chain reaction (PCR) techniques indicate that at least half of all infections in maternal venous blood are missed by light microscopy or rapid diagnostic tests. The impact of these subpatent infections on maternal and birth outcomes remains unclear. METHODS: In a cohort of women co-enrolled in a clinical trial of intermittent treatment with sulfadoxine-pyrimethamine (SP) plus azithromycin for the prevention of LBW (< 2500 g) in Papua New Guinea (PNG), P. falciparum infection status at antenatal enrolment and delivery was assessed by routine light microscopy and real-time quantitative PCR. The impact of infection status at enrolment and delivery on adverse birth outcomes and maternal haemoglobin at delivery was assessed using logistic and linear regression models adjusting for potential confounders. Together with insecticide-treated bed nets, women had received up to 3 monthly intermittent preventive treatments with SP plus azithromycin or a single clearance treatment with SP plus chloroquine. RESULTS: A total of 9.8% (214/2190) of women had P. falciparum (mono-infection or mixed infection with Plasmodium vivax) detected in venous blood at antenatal enrolment at 14-26 weeks' gestation. 4.7% of women had microscopic, and 5.1% submicroscopic P. falciparum infection. At delivery (n = 1936), 1.5% and 2.0% of women had submicroscopic and microscopic P. falciparum detected in peripheral blood, respectively. Submicroscopic P. falciparum infections at enrolment or at delivery in peripheral or placental blood were not associated with maternal anaemia or adverse birth outcomes such as LBW. Microscopic P. falciparum infection at antenatal enrolment was associated with anaemia at delivery (adjusted odds ratio [aOR] 2.00, 95% confidence interval [CI] 1.09, 3.67; P = 0.025). Peripheral microscopic P. falciparum infection at delivery was associated with LBW (aOR 2.75, 95% CI 1.27; 5.94, P = 0.010) and preterm birth (aOR 6.58, 95% CI 2.46, 17.62; P < 0.001). CONCLUSIONS: A substantial proportion of P. falciparum infections in pregnant women in PNG were submicroscopic. Microscopic, but not submicroscopic, infections were associated with adverse outcomes in women receiving malaria preventive treatment and insecticide-treated bed nets. Current malaria prevention policies that combine insecticide-treated bed nets, intermittent preventive treatment and prompt treatment of symptomatic infections appear to be appropriate for the management of malaria in pregnancy in settings like PNG.

Susceptibility of human villous (BeWo) and extravillous (HTR-8/SVneo) trophoblast cells to Toxoplasma gondii infection is modulated by intracellular iron availability.

Congenital toxoplasmosis is a serious health problem that can lead to miscarriage. HTR-8/SVneo is a first trimester extravillous trophoblast, while BeWo is a choriocarcinoma with properties of villous trophoblast cells. In the placenta, iron is taken up from Fe-transferrin through the transferrin receptor being the ion an important nutrient during pregnancy and also for Toxoplasma gondii proliferation. The aim of this study was to evaluate the role of iron in T. gondii proliferation in BeWo and HTR-8/SVneo cells and in human chorionic villous explants. The cells were infected with T. gondii, iron supplemented or deprived by holo-transferrin or deferoxamine, respectively, and parasite proliferation and genes related to iron balance were analyzed. It was verified that the addition of holo-transferrin increased, and DFO decreased the parasite multiplication in both trophoblastic cells, however, in a more expressive manner in HTR-8/SVneo, indicating that the parasite depends on iron storage in trophoblastic cells for its growth. Also, tachyzoites pretread with DFO proliferate normally in trophoblastic cells demonstrating that DFO itself does not interfere with parasite proliferation. Additionally, T. gondii infection induced enhancement in transferrin receptor mRNA expression levels in trophoblastic cells, and the expression was higher in HTR-8/SVneo compared with BeWo. Finally, DFO-treatment was able to reduce the parasite replication in villous explants. Thus, the iron supplementation can be a double-edged sword; in one hand, it could improve the supplement of an essential ion to embryo/fetus development, and on the other hand, could improve the parasite proliferation enhancing the risk of congenital infection.

Epidemiology of congenital Chagas disease 6 years after implementation of a public health surveillance system, Catalonia, 2010 to 2015.

BackgroundChagas disease is endemic in Latin America and affects 8 million people worldwide. In 2010, Catalonia introduced systematic public health surveillance to detect and treat congenital Chagas disease.AimThe objective was to evaluate the health outcomes of the congenital Chagas disease screening programme during the first 6 years (2010-2015) after its introduction in Catalonia.MethodsIn a surveillance system, we screened pregnant women and newborns and other children of positive mothers, and treated Chagas-positive newborns and children. Diagnosis was confirmed for pregnant women and children with two positive serological tests and for newborns with microhaematocrit and/or PCR at birth or serology at age 9 months.ResultsFrom 2010 to 2015, the estimated screening coverage rate increased from 68.4% to 88.6%. In this period, 33,469 pregnant women were tested for Trypanosoma cruzi and 937 positive cases were diagnosed. The overall prevalence was 2.8 cases per 100 pregnancies per year (15.8 in Bolivian women). We followed 82.8% of newborns until serological testing at age 9-12 months and 28 were diagnosed with Chagas disease (congenital transmission rate: 4.17%). Of 518 siblings, 178 (34.3%) were tested and 14 (7.8%) were positive for T. cruzi. Having other children with Chagas disease and the heart clinical form of Chagas disease were maternal risk factors associated with congenital T. cruzi infection (p < 0.05).ConclusionThe increased screening coverage rate indicates consolidation of the programme in Catalonia. The rate of Chagas disease congenital transmission in Catalonia is in accordance with the range in non-endemic countries.

Toxoplasma Screening Results of 84587 Pregnant Women in a Tertiary Referral Center in Turkey.

Aim: To determine the seroprevalence of Toxoplasma in a tertiary referral center in Turkey and to discuss the benefits and drawbacks of routine antenatal screening. Materials and methods: A serologic test for Toxoplasma is free of charge for all pregnant women as part of routine antenatal care at their first prenatal visit. The study was conducted between 2008 and 2017. Results: The frequency of Toxoplasma IgG and IgM seropositivity was 22.3% and 0.64%, respectively. Low avidity was detected in 142 patients and 60 PCR tests were performed with no positive result. A total of 33 mothers with low IgG avidity and negative PCR received prophylactic treatment, and no congenital toxoplasmosis was documented in this study. Conclusion: Universal screening for Toxoplasma in pregnancy is a subject of debate. As the prevalence in Turkey is higher compared to other countries, more studies are needed to identify the necessity of routine screening.

[Microbiological analysis of the maternal genital tract and umbilical cord blood and its association with neonatal damage]. / Análisis microbiológico del tracto genital materno y de la sangre del cordón umbilical en relación con el daño neonatal.

The etiology leading to neonatal damage is multifactorial, being genital infections one of the causes. The objective of the study was to identify microorganisms of the maternal genital tract that are associated with neonatal damage, in order to prevent future perinatal complications. Seven hundred and eleven pregnant patients attended their prenatal control during the period January 2010-July 2013. Ureaplasma urealyticum and Mycoplasma hominis presence was investigated in umbilical cord blood by metabolic substrates (Micofast-Biomerieux) and that of T.vaginalis, by PCR using specific primers. The microbiological study of the vaginal contents of 288 pregnant patients at weeks 35 to 37 was performed by conventional methods, adding the modified thioglycolate culture for T.vaginalis. GroupB streptococcus (GBS) was investigated in anorectal and vaginal introitus swabs, using selective broth enrichment and subsequent isolation in chromogenic medium. The χ2 Yates test and Fisher's test were used for independent samples. A p value <0.05 was considered statistically significant. The pathogens significantly related to neonatal damage were M.hominis (p=0.03), T.vaginalis (p=0.03), and BV (p=0.02). Main complications were preterm birth, premature rupture of membranes (PRM), low weight and Apgar score ≤7. U.urealyticum (p=0.35), Candidaspp. (p=0.94) and GBS (p=0.18) were not related to neonatal damage. Since different microorganisms of the maternal genital tract were related to neonatal damage, it is very important to perform the microbiological study of vaginal contents during pregnancy to prevent possible maternal and perinatal complications.

Etiology of Placental Plasmodium falciparum Malaria in African Women.

Plasmodium falciparum parasites causing placental malaria express the VAR2CSA type of the clonally variant antigen family erythrocyte membrane protein 1 (PfEMP1). This enables evasion of preexisting immunity and results in placental accumulation of infected erythrocytes. We present data on seasonal variation in levels of VAR2CSA-specific immunoglobulin G (IgG) and IgG specific for a placental malaria-unrelated PfEMP1 protein among Ghanaian women at their first antenatal visit. Our results indicate that placental malaria does not require recent exposure to infected mosquitoes, in contrast to malaria in general. This has implications for the impact of insecticide-treated bed nets on placental malaria incidence and for antenatal care in woman with preexisting immunity.

Placental Sequestration of Plasmodium falciparum Malaria Parasites Is Mediated by the Interaction Between VAR2CSA and Chondroitin Sulfate A on Syndecan-1.

During placental malaria, Plasmodium falciparum infected erythrocytes sequester in the placenta, causing health problems for both the mother and fetus. The specific adherence is mediated by the VAR2CSA protein, which binds to placental chondroitin sulfate (CS) on chondroitin sulfate proteoglycans (CSPGs) in the placental syncytium. However, the identity of the CSPG core protein and the cellular impact of the interaction have remain elusive. In this study we identified the specific CSPG core protein to which the CS is attached, and characterized its exact placental location. VAR2CSA pull-down experiments using placental extracts from whole placenta or syncytiotrophoblast microvillous cell membranes showed three distinct CSPGs available for VAR2CSA adherence. Further examination of these three CSPGs by immunofluorescence and proximity ligation assays showed that syndecan-1 is the main receptor for VAR2CSA mediated placental adherence. We further show that the commonly used placental choriocarcinoma cell line, BeWo, express a different set of proteoglycans than those present on placental syncytiotrophoblast and may not be the most biologically relevant model to study placental malaria. Syncytial fusion of the BeWo cells, triggered by forskolin treatment, caused an increased expression of placental CS-modified syndecan-1. In line with this, we show that rVAR2 binding to placental CS impairs syndecan-1-related Src signaling in forskolin treated BeWo cells, but not in untreated cells.

Prevalence and Detection of Trichomonas vaginalis in HIV-Infected Pregnant Women.

BACKGROUND: Trichomonas vaginalis is a sexually transmitted infection associated with increased transmission of HIV and significant adverse birth outcomes; culture and polymerase chain reaction (PCR) are commonly used in diagnosis. METHODS: Consenting HIV-infected pregnant women were recruited from clinics in South Africa and screened for T. vaginalis using PCR. Polymerase chain reaction-positive women provided an additional sample for culture. We compared T. vaginalis detection between PCR and culture, and investigated how PCR cycle threshold (Ct) values differ among culture results. RESULTS: A total of 359 women were enrolled and 76 (20%) tested T. vaginalis PCR positive. Cultures were obtained from 61 of the PCR-positive women, and 38 (62%) were culture positive. The median baseline Ct of the PCR-positive/culture-positive group was 22.6 versus 38.0 among those who were PCR positive/culture negative (P < 0.001). Culture-positive cases had lower Ct values (higher DNA load); a Ct value less than 30 predicted positivity with a sensitivity of 97% and a specificity of 96%. CONCLUSIONS: Culture was positive in roughly half of PCR-positive cases. The culture-negative cases had significantly higher Ct values, indicating a lower concentration of T. vaginalis DNA. A Ct value of 30 provides a reliable threshold for predicting culture positivity. The clinical significance of culture-negative infections detected by PCR is still unclear.

The prevalence of submicroscopic Plasmodium falciparum gametocyte carriage and multiplicity of infection in children, pregnant women and adults in a low malaria transmission area in Southern Ghana.

BACKGROUND: The gametocyte stage of Plasmodium falciparum is considered an important target for disrupting malaria transmission. Indications are that various demographic groups, such as children and pregnant women may differ in risk of harbouring gametocytes, which may be crucial for targeted control. In this study, the relationship between the prevalence and multiplicity of P. falciparum, asexual parasite infections and gametocytaemia was assessed in three different demographic groups in an area of southern Ghana with low malaria endemicity. Levels of antibody responses to Pfs230 were also assessed as a proxy for the presence of gametocytes. METHODS: The study involved multiple cross-sectional sampling of children (N = 184, aged 2-15 years), male and non-pregnant female adults (N = 154, aged 16-65 years) and pregnant women (N = 125, aged 18-45 years) from Asutsuare in the Shai Osudoku District of Greater Accra Region in Ghana. Asexual parasitaemia was detected by microscopy and PCR, and gametocytaemia was assessed by Pfs25-real time PCR. Multiclonal P. falciparum infections were estimated by msp2 genotyping and an indirect ELISA was used to measure plasma IgG antibodies to Pfs230 antigen. RESULTS: Overall, children and pregnant women had higher prevalence of submicroscopic gametocytes (39.5% and 29.7%, respectively) compared to adults (17.4%). Multiplicity of infection observed amongst children (3.1) and pregnant women (3.9) were found to be significantly higher (P = 0.006) compared with adults (2.7). Risk of gametocyte carriage was higher in individuals infected with P. falciparum having both Pfmsp2 3D7 and FC27 parasite types (OR = 5.92, 95% CI 1.56-22.54, P = 0.009) compared with those infected with only 3D7 or FC27 parasite types. In agreement with the parasite prevalence data, anti-Pfs230 antibody levels were lower in gametocyte positive adults (ß = - 0.57, 95% CI - 0.81, - 0.34, P < 0.001) compared to children. CONCLUSIONS: These findings suggest that children and pregnant women are particularly important as P. falciparum submicroscopic gametocyte reservoirs and represent important focus groups for control interventions. The number of clones increased in individuals carrying gametocytes compared to those who did not carry gametocytes. The higher anti-gametocyte antibody levels in children suggests recent exposure and may be a marker of gametocyte carriage.