Acute Maternal Infection Research Articles

Clinical utility of maternal TORCH screening in fetal growth restriction: A retrospective two-centre study.

The aim of this study was to evaluate the indications for maternal TORCH (Toxoplasma gondii, rubella, cytomegalovirus (CMV), and herpes simplex virus (HSV)) serology, with a focus on the yield in isolated fetal growth restriction (FGR). A retrospective review of antenatal TORCH testing between January 2014 and December 2018 was carried out at two hospitals in Melbourne, Australia. TORCH testing ordered for pregnancy losses and stillbirth was excluded. Medical records of 718 pregnancies were reviewed, representing 760 fetuses. Isolated FGR was the indication for TORCH screening in 71.2% of pregnancies. Screens ordered for isolated FGR were positive in 7.4% (95% CI 5.5-10.0%). There were 49 positive maternal immunoglobulin M (CMV = 34, Toxoplasma = 15). Two acute maternal infections during pregnancy were diagnosed (CMV = 1, Toxoplasma = 1), with both screens ordered to assess symptomatic maternal illness. There was one neonatal CMV infection, born to a woman with symptomatic primary CMV. No maternal or neonatal rubella or HSV infections were identified. We found a diagnostic yield of TORCH screening for isolated FGR of 0.0% (95% CI 0.00-0.8%). An estimated AUD$64 269.75 was expended on maternal TORCH screens in this study. Maternal TORCH testing for isolated FGR is of no diagnostic yield and should be abandoned.

Breastfeeding Rates During the COVID-19 Pandemic in Germany: Data from the CRONOS Registry.

SARS-CoV-2 infection and COVID-19 disease are thought to have an impact on breastfeeding rate - besides other known peripartal issues. Data of the national CRONOS registry regarding breastfeeding behavior in 6,746 women was analyzed regarding the time window between maternal SARS-CoV-2 infection and time of delivery. In addition, other influencing factors like the predominant viral variant, maternal disease severity, and gestational age at delivery were taken into account. Our data suggest that within the variables analyzed, in the case of acute maternal infection (<14 days before birth), breastfeeding behavior improved with increasing gestational age at birth (p<0.0001), with less severe maternal illness (p<0.0001) and as the pandemic progressed with less virulent viral variants (p=0.01). When adjusting for COVID-19-associated and non-associated factors, rooming-in remains the most important factor positively influencing breastfeeding behavior. With regards to the benefits for mother and infants from breastfeeding, a separation of mother and child even in case of infectious settings should be avoided.

Prevalence and associated risk factors of Toxoplasma gondii infection in sheep and aborted women in Egypt

Toxoplasmosis has been associated with economic and public health concerns due to abortion in humans and animals. Detection for the presence of anti-Toxoplasma gondii antibodies in sera of 174 healthy sheep (IgG) and sera of 89 aborted women (IgG, IgM, and IgG avidity) using enzyme-linked immunosorbent assay and T. gondii in 59 sheep milk samples identified by PCR. The primary risk factors for sheep and women seropositive samples were also analyzed. Relatively higher seroprevalence of T. gondii, 62.6%, was recorded in sheep than 57.3% in aborted women. The IgM/IgG antibody responses in aborted women were 42.7%, 41.6%, 15.7%, and 0% for IgM -ve/IgG -ve (negative toxoplasmosis), IgM -ve/IgG +ve (chronic toxoplasmosis), IgM +ve/IgG +ve (maternal infection) and IgM +ve/IgG -ve (acute infection), respectively. IgM and IgG-positive samples showed a low avidity rate 14.3%, denoting acute maternal infection, while a much higher rate 78.6%, denoting chronic maternal infection. Molecular investigation of T. gondii in sheep milk samples revealed that 28.8% were positive by PCR at 470-bp. The respectable significant association between many risk factors and the seroprevalence of T. gondii in humans and sheep was recorded. The current study indicates elevated toxoplasmosis antibodies in sheep and aborted women from El-Beheira and Alexandria governorates, Egypt. Additionally, it demonstrates a correlation between age, mutton intake, miscarriage, cat exposure, drinking water source, and breeding practices with seropositivity to T. gondii. These results largely confirm the need for greater in-depth toxoplasmosis epidemiological research and public health education initiatives.

LB1534. Cord blood and maternal cytokine levels following SARS-CoV-2 infection during pregnancy

Abstract Background Pregnant people and fetuses are uniquely vulnerable to SARS-CoV-2, a driver of inflammation and immune dysregulation. Prior investigations have shown that pregnant people with SARS-CoV-2 are at higher risk of severe illness, mortality, and obstetric complications. We investigated the impact of SARS-CoV-2 infection severity and latency on maternal and infant cytokine levels. Methods We collected maternal blood and cord blood at delivery from mother-infant dyads (Chicago, IL; 3/2020-1/2022). A multiplex cytokine panel (IsoPlexis) was run on plasma from 93 SARS-CoV-2 infected dyads and 32 matched controls. Clinical data was abstracted by chart review, including latency (acute being ≤14 days and distant &amp;gt;14 days from SARS-CoV-2 infection to delivery) and severity (NIH criteria: asymptomatic, mild, moderate, severe/critical). Kruskal-Wallis tests with post-hoc pairwise Dunn Tests were used (α=0.05). Results SARS-CoV-2 exposed infants had lower levels of MIP-1b (p=0.037) and PDGF (p=0.008) than controls [Fig 1]. There were no differences in maternal blood cytokines at time of delivery following SARS-CoV-2 infection during pregnancy (pooled analysis of all SARS-CoV-2). Stratifying by latency, acutely exposed infants showed higher levels of MCP-1 than controls or those with distant maternal SARS-CoV-2 (p=0.016). There were no significant differences in maternal cytokines between control, acute, and distant SARS-CoV-2. In mothers with acute SARS-CoV-2, differences in levels of IL-1B (p=0.011) and IL-10 (p=0.046) were observed across severity groups, with a significant linear trend for each among severity groups (p for trend &amp;lt; 0.001, respectively). Severe/critical acute infection resulted in higher maternal granzyme and IL-8 than mild infection (p=0.037 and 0.047) [Fig 2]. There were no differences across severity groups in 1) mothers with distant infection, 2) infants with acute maternal infection, or 3) infants with distant maternal infection. Maternal and infant cytokine levels in acute SARS-CoV-2 infection across severity Conclusion Cytokine levels in SARS-CoV-2 positive dyads were altered only in the setting of acute or more severe infection and demonstrated anti-inflammatory, anti-viral, and anti-angiogenic responses. In acute infection, greater severity drives higher levels of both a pro- and anti-inflammatory cytokine in pregnant people. Disclosures All Authors: No reported disclosures.

2127. Is Routine TORCH Screening Necessary For Isolated Intrauterine Growth Restriction?

Abstract Background Perinatal TORCH infections (Toxoplasma gondii, rubella, cytomegalovirus [CMV], herpes simplex virus [HSV]) cause significant fetal and neonatal morbidity and mortality. While perinatal infections are associated with a variety of clinical manifestations in the fetus, they rarely cause isolated intrauterine growth restriction (IUGR). TORCH screens are often ordered to investigate isolated IUGR, but there is limited evidence to support screening for these infections in the absence of other ultrasound abnormalities. Methods A retrospective review of antenatal TORCH testing between January 2014 and December 2018 was carried out at two hospitals in Melbourne, Australia. Records were reviewed to identify indications for testing, serology results, and subsequent antenatal investigations. Neonatal outcomes were also evaluated. Serology performed for stillbirth or pregnancy losses were excluded. Results Medical records of 718 pregnancies were reviewed, representing 760 fetuses. 82.5% of screens were ordered in the third trimester, with 43.5% ordered after 32 weeks gestation. TORCH serology was performed for the following indications: isolated IUGR (71.2%), neurological abnormality (6.8%), echogenic bowel (3.4%), and maternal illness (1.7%). Screens ordered for isolated IUGR were positive in 7.4% (95% CI 5.5-10.0%). TORCH screening identified 49 positive maternal IgM results (CMV = 34, toxoplasma = 15) Two acute maternal infections during pregnancy were diagnosed (CMV = 1, toxoplasma = 1). Both were identified due to symptomatic maternal illness. There was one confirmed neonatal CMV infection. Eight women did not have follow-up to determine the significance of a positive IgM result. No TORCH screen changed maternal management or neonatal outcomes. Rubella IgM was ordered in 83.5% of women who had clearly documented evidence of prior rubella immunity. No acute HSV infections were identified. Conclusion Antenatal TORCH screening for IUGR is of minimal utility and is often performed as a reflex rather than in response to specific clinical syndromes. A more guided approach with selective testing is needed. Disclosures All Authors: No reported disclosures.

Antepartum acute maternal infection: Is the preterm neonate protected?

One of two preterm neonates born < 29 weeks gestational age exhibits some degree of cerebral white matter injury, the etiology of which remains unclear. We hypothesized that systemic maternal inflammation from infection leads to fetal neuroinflammation, which has a strong role in the pathogenesis of poor short-term and long-term neonatal outcomes. The aim of this study was to examine the relationship between antepartum maternal infection and short-term neonatal outcomes. We conducted a retrospective cohort study of preterm neonates < 29 weeks of gestational age born at our institution from 01/2010-12/2020. We excluded those with neonates receiving comfort care in the delivery room or with congenital or chromosomal abnormalities. Maternal data was extracted including co-morbidities, obstetric outcomes and complications, and maternal infections and treatments. Maternal antepartum infection status was categorized as (1) no infection, (2) non-severe acute infection and (3) severe acute infection. Infant data extracted included short-term outcomes of bronchopulmonary dysplasia, necrotizing enterocolitis, sepsis, intraventricular hemorrhage, pneumothorax, pneumonia, pulmonary hypertension, days ventilated, days on CPAP, and maximum FiO2. Analyses included c2, Fisher’s exact test, one-way analysis of variance, and Kruskal-Wallis test with p < .05 considered significant. 1121 neonates were born < 29 weeks to 983 women; 788 (70.3%) had no infection documented prenatally, 240 (21.4%) an acute non-severe infection, and 93 (8.3%) an acute severe infection. Rates of prolonged rupture of membranes were higher in the severe acute infection group whereas rates of preeclampsia and cesarean section were lower (Table 1). The presence of any acute infection did not correlate with short-term neonatal outcomes (Table 2). Acute maternal infection does not correlate with short-term neonatal outcomes. The neonate may be protected from maternal inflammation through placental-mediate mechanisms.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Performance of a Toxo IgM prototype assay for the diagnosis of maternal and congenital Toxoplasma infections.

Background Testing for anti-Toxoplasma immunoglobulin (Ig)M is of main importance in the context of pregnancy to promptly alert to an acute maternal infection prior to the detection of IgG and to identify infected newborns. Their absence helps exclude a recent maternal infection in the presence of IgG. Methods The performance of a Toxo IgM immunocapture prototype assay (bioMérieux, France) was compared with that of the VIDAS® Toxo IgM and the ARCHITECT® Toxo IgM (Abbott, Germany) assays at Grenoble and Lyon (France). A total of 1446 sera were sampled from (i) 1054 pregnant women found by routine workup to have no infection (n = 843), an acute infection (<4 months) (n = 28) or a chronic infection (>4 months) with residual (n = 120) or no IgM (n = 62); (ii) 50 three-serum panels sampled immediately after a maternal seroconversion; (iii) 242 samples taken in 41 children with a congenital toxoplasmosis (n = 122) and in 40 uninfected children (n = 120). Results In pregnant women, the overall agreement with the VIDAS® assay was 99.23% (CI: 99.16-99.27) and that with the ARCHITECT® assay was 99.14% (CI: 99.07-99.17). Sensitivity of the Toxo IgM prototype assay was 100% (CI: 87.66-100.00) and specificity was 99.64% (98.96-99.93). In acute maternal infections, IgM assays were detected as early with the prototype as with the other two. In the congenitally infected children, IgM were detected on their first sample in 25/40 with the prototype vs. 23/40 with the VIDAS® test. No uninfected child had positive IgM. Conclusion The prototype performed comparably to the ARCHITECT® and VIDAS® Toxo IgM assays for the diagnosis of maternal and congenital toxoplasmosis.

Rubella in Pregnancy

AbstractRubella, commonly known as ‘German Measles’ is a common childhood viral disease that may affect adults as well. More than half of the infections are either asymptomatic or present with mild flu like illness with a typical maculopapular rash. In contrast, primary rubella infection in pregnancy, especially in the first trimester, can have serious consequences, namely miscarriage, intrauterine fetal demise or congenital rubella syndrome (CRS). WHO recognizes CRS as the ‘leading vaccine preventable cause of birth defects’. Antenatal management primarily is based on testing for immunity in the first trimester and recognizing acute maternal infection. A correct interpretation of maternal serology using IgG avidity along with IgM and IgG is imperative to avoid false positive diagnoses. Diagnosis of fetal infection is by detection of Rubella virus specific RTPCR in amniotic fluid and is indicated if maternal seroconversion is seen in the periconceptional period and/or the first trimester or if there are ultrasound features suggestive of fetal infection. Since there is no treatment available to either prevent mother to child transmission or to treat fetal infection, the mainstay is prevention. India is amongst the 11 countries of WHO South East Asia Region who are committed to control of Rubella and CRS by 2020.

PLACENTAL CYTOPATHIC DAMAGE FACTOR DUE TO PARVOVIRUS B19 – AS A HALLMARK OF INTRAUTERINE SYMPTOMATHY OF INFECTED FETUS

Aim of the work. The focus of this study was to analyze the frequency of fetal intrauterine symptomatic realization as a result of B19 parvovirus infection of pregnant women during I and II gestation periods, with the combination of determination the levels of alpha-fetoprotein in maternal serum blood and histopathological investigation of placenta in cases of negative effects for infected fetuses. Materials and methods. A total of 478 pregnant women were at risk of infection and screened for parvovirus B19. The study was based on serological, morphological and virological testing of fetuses from mothers with confirmed parvovirus B19 infection. Infection of pregnant women was detected by serological diagnosis of specific antibodies IgM and IgG to parvovirus B19. Intrauterine fetal infection was confirmed by polymerase chain reaction method. Levels of alpha-fetoprotein in meternal venous blood were detected using an immunochemical test method. An antenatal diagnosis of hydrops fetalis was confirmed by ultrasound scanning. Placenta from the 8 infected fetuses was studied histologically with hematoxylin and eosin staining using electron microscope during gestational periods of 12-22 weeks. Statistical analysis of the obtained data was carried out using nonparametric statistics with the definition of Fisher's criterion. Results and discussion. The average gestational period of symptomatic manifestations of intrauterine fetal infection was 19.9±0.5 weeks of gestation. It was established that in 33 of cases were confirmed the intrauterine infection due to parvovirus B19 by using the morphological placenta tissue analysis. The research found that the levels of maternal serum alpha-fetoprotein was significantly higher (in 2.17 times) in group of fetuses who suffered from fetal hydrops and in cases of intrauterine fetal death before detecting the general echographic sings of fetal failure (p˂0.05). It will be very important to compare this indicator with the Doppler ultrasound measurements of the human fetal middle cerebral artery peak systolic velocity (MCA PSV) and blood flow parameters in the fetal ductus venosus and to predict the possibility of poor perinatal outcomes. It was identified a cytopathic effect in placental cells viral origin and detected in cells of the cytotrophoblast, syncytiotrophoblast, endothelial cells, and blood cells. Conclusions. Parvovirus B19 fractions were visualized in 100 % of cases of miscarriages with fetal hydrops and placental edema during 12-22 weeks of gestation, while acute maternal parvovirus infection (with the detection of IgM against to parvovirus B19) was diagnosed by immunoassay only in 62.5 % of cases. Detection of B19 particles in placental tissue from fetuses with non-immune origin hydrops is an auxiliary method in the diagnosis of vertical transmission of parvovirus during pregnancy. It is more preferable to estimate the levels of alpha-fetoprotein in maternal serum blood in case of parvovirus B19 affected pregnancies as raising rates of this marker may be an early prediction hallmark for adverse fetal outcome.

Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current Clinical Practice.

Primary Toxoplasma gondii infection is usually subclinical, but cervical lymphadenopathy or ocular disease can be present in some patients. Active infection is characterized by tachyzoites, while tissue cysts characterize latent disease. Infection in the fetus and in immunocompromised patients can cause devastating disease. The combination of pyrimethamine and sulfadiazine (pyr-sulf), targeting the active stage of the infection, is the current gold standard for treating toxoplasmosis, but failure rates remain significant. Although other regimens are available, including pyrimethamine in combination with clindamycin, atovaquone, clarithromycin, or azithromycin or monotherapy with trimethoprim-sulfamethoxazole (TMP-SMX) or atovaquone, none have been found to be superior to pyr-sulf, and no regimen is active against the latent stage of the infection. Furthermore, the efficacy of these regimens against ocular disease remains uncertain. In multiple studies, systematic screening for Toxoplasma infection during gestation, followed by treatment with spiramycin for acute maternal infections and with pyr-sulf for those with established fetal infection, has been shown to be effective at preventing vertical transmission and minimizing the severity of congenital toxoplasmosis (CT). Despite significant progress in treating human disease, there is a strong impetus to develop novel therapeutics for both the acute and latent forms of the infection. Here we present an overview of toxoplasmosis treatment in humans and in animal models. Additional research is needed to identify novel drugs by use of innovative high-throughput screening technologies and to improve experimental models to reflect human disease. Such advances will pave the way for lead candidates to be tested in thoroughly designed clinical trials in defined patient populations.

Congenital Toxoplasmosis in Tunisia: Prenatal and Neonatal Diagnosis and Postnatal Follow-up of 35 Cases.

Congenital toxoplasmosis (CT) results from transplacental passage of Toxoplasma gondii to the fetus during acute maternal infection. Our study aims to report clinical and biological patterns of 35 cases of CT diagnosed at the department of the Parasitology of the Pasteur Institute of Tunis and to access the performance of prenatal and early postnatal diagnosis techniques. Serological screening of maternal infection was performed by Immunoglobulin (Ig) M and IgG detection and IgG avidity determination. Prenatal diagnosis was based on both Toxoplasma DNA detection in the amniotic fluid and monthly ultrasound examinations. polymerase chain reaction analysis on amniotic fluid, performed only in 15 cases, detected Toxoplasma's DNA in five cases (33.3%). Ultrasound examination did not reveal any morphological abnormalities. Thirty newborns had serological criteria of Toxoplasma infection. Congenital toxoplasmosis diagnosis was confirmed in 23 cases (76.6%) by immunoblot. Among the 35 born-infants, five (14.3%) were symptomatic: three had chorioretinitis at the first clinical ocular examination, one had neurological symptoms (seizures) with positive parasite DNA in cerebral spinal fluid, and one had both ophthalmological and neurological damages- chorioretinitis and intracranial calcifications in the computed tomography scan. Thirty-four of 35 infected children were treated with pyrimethamine-sulfadiazine combination. Four (11.7%) of the treated infants showed abnormal hematological values because of the treatment side effect. Serological rebound was observed in seven infants. A screening program and a diagnostic algorithm in pregnant women should be implemented in Tunisia to improve the follow-up of seronegative ones and to prevent CT cases.

АССОЦИАТИВНАЯ СВЯЗЬ ИНФЕКЦИОННО-ВОСПАЛИТЕЛЬНЫХ ЗАБОЛЕВАНИЙ ПРИ БЕРЕМЕННОСТИ И ТЯЖЁЛОЙ ПРЕЭКЛАМПСИИ

Materials and methods. This retrospective case-control study enrolled 50 women with severe preeclampsia and 50 control women with spontaneous singleton pregnancy. Median age of women ranged from 20 to 35 years. All women did not have a history of hypertension, autoimmune, metabolic, renal, or cardiac diseases, and preeclampsia before this pregnancy. We have analyzed χ 2 , odds ratio (OR) and its 95% confidence intervals (95% Cl). Results. We found significant association between maternal systemic infectious and severe preeclampsia (OR = 49.6; 95% Cl 13.05-188.64). The risk of severe preeclampsia were significantly lower in patients with local infections of the lower genital tract (OR = 4.5; 95% Cl 1.49-6.71). Asymptomatic bacteriuria is associated with the highest risk of severe preeclampsia (OR = 17.0; 95% Cl 4.66-61.81). Acute gravidarum pyelonephritis showed lower association with severe preeclampsia (OR = 5.4; 95% Cl 1.69-10.54). We did not observe increased risk of severe preeclampsia with acute respiratory infections (OR = 2.0; 95% Cl 0.71-4.69). Acute non-specific bacterial vaginitis and acute candidiasis vulvovaginitis were found to be risk factors of severe preeclampsia (OR = 6.7; 95% Cl 1.90-11.02 and OR = 4.3; 95% Cl 1.45-9.99 respectively). Cytomegalovirus infection (2 %), toxoplasmosis (2 %), Chlamydia trachomatis cervicitis (4 %), acute Trichomonas colpitis (2 %) and bacterial vaginosis (4 %) were found only in patients with severe preeclampsia. Conclusion. Our data support that acute maternal infection is associated with an increased risk of severe preeclampsia in healthy women with singleton pregnancy. Systemic inflammatory response might be the main potential mechanisms related to infections and enhanced development of severe preeclampsia. Further research is required to elucidate the underlying mechanism of this association.

Missed Opportunities for Preventing Perinatal Transmission of Human Immunodeficiency Virus, Florida, 2007-2014.

Despite declining numbers of perinatally exposed infants, an increase in perinatal human immunodeficiency virus (HIV) infections from 2011 to 2013 prompted this study to identify missed perinatal HIV prevention opportunities. Deidentified records of children born from 2007 through 2014, exposed to HIV perinatally, and reported to the Florida Department of Health were obtained. Crude relative risks (RRs) and 95% confidence intervals (CIs) for factors associated with perinatal transmission, nondiagnosis of maternal HIV infection, and nonreceipt of antiretroviral medication were calculated. Of the 4337 known singleton births exposed to maternal HIV infection, 70 (1.6%) were perinatally infected. Among perinatal transmission cases, more than one-third of mothers used illegal drugs or acquired a sexually transmitted infection during pregnancy. Perinatal transmission was most strongly associated with maternal HIV diagnosis during labor and delivery (RR 5.66, 95% CI 2.31-13.91) or after birth (RR 26.50, 95% CI 15.44-45.49) compared with antenatally or prenatally. Among the 29 women whose infection was not known before pregnancy and whose child was perinatally infected, 18 were not diagnosed during pregnancy; 12 had evidence of an acute HIV infection, and 6 had no prenatal care. Late diagnosis of maternal HIV infection appeared to be primarily the result of acute maternal infections and inadequate prenatal care. In Florida, effective programs to improve utilization of prenatal care and detection and primary prevention of prenatal acute infection are needed.

Incidence of Symptomatic Congenital Toxoplasmosis During Ten Years in a Brazilian Hospital.

Population seroprevalence and rates of mother-to-child transmission are important in determining the incidence of congenital toxoplasmosis. (CT) Mother-to-child transmission depends on the timing of acute maternal infection and treatment during pregnancy. The incidence of CT varies widely across geographic regions, ranging from 1 to 10 cases per 10,000 live births. The incidence of symptomatic disease varies from 0.15 to 0.34 cases per 10,000. This is a review of patients treated at a pediatric CT clinic at a university hospital in the south of Brazil, from 2004 to 2014. The annual incidence of CT varied from 0 to 14 cases per 10,000 live births, with a mean incidence of 6 cases per 10,000 during the 10 years studied (CI 95%: 3.02-8.91). The incidence of symptomatic CT varied from 0 to 9 cases per 10,000 live births, with a mean incidence of 5 per 10,000 (CI 95%: 2.44-6.94). There were 5 (14.3%) asymptomatic cases. The main findings were retinochoroiditis (54%), intracranial calcifications (37.5%) and altered cerebrospinal fluid (37.5%). The incidence of CT and the rate of symptomatic cases were in accordance with the previous data from other studies in Brazil, being significantly higher than in previous North American and European studies.

Frequency of Toxoplasma Infection Among Pregnant Women and Their Newborn in Kashan, Iran

test. Results: Five (0.63%) and 341 (42.7%) were positive for acute and chronic infections. A 400 bp band was seen in 3 newborns of acute maternal infections. The incidence of neonatal toxoplasmosis was 3.7 per 1000. Only one neonate of the acute maternal toxoplasmosis had jaundice. Conclusions: The rate of maternal and neonatal toxoplasmosis, were higher than the world. Jaundice was only sign in newborn with Toxoplasma gondii infection.

Antibodies for prevention of mother-to-child transmission of HIV-1.

Although antiretroviral (ARV) prophylaxis can reduce mother-to-child transmission (MTCT) of HIV-1 to less than 2%, one-quarter of a million infants continue to be infected with HIV-1 annually. ARV prophylaxis alone will fail to eliminate infant HIV-1 infection because of issues of maternal adherence, toxicities, ARV-resistant virus strains, and acute maternal infection. Effective maternal and/or infant immunization will likely be required to achieve the goal of an HIV-free generation. This article describes recent studies of antibody responses that protect against vertical HIV-1 transmission. Studies have shown that maternal neutralization breadth is not a critical factor in MTCT, yet the ability of maternal plasma to neutralize autologous virus variants may be important in infant protection. There is also new evidence that infants mount robust and durable antibody responses to HIV-1 envelope following vaccination and can develop broad neutralization during infection. Finally, passive immunization of infants with highly potent and broad neutralizing antibodies may be an effective strategy to protect infants against infection with postnatally transmitted variants. Defining the characteristics of maternal and infant antibody responses that protect against MTCT will inform development of effective passive and active immunization strategies that will likely be required to eliminate pediatric HIV-1.

Infant HIV-1 vaccines: supplementing strategies to reduce maternal-child transmission.

Despite the success of maternal antiretroviral therapy (ART) to prevent mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1), more than 200 000children continue to acquireHIV-1 annually. Infants account for roughly 10% of new HIV-1 infections globally despite making up less than 2%of the world’s population. Moreover, the decline in infant HIV-1 acquisition with implementation of wide-scale maternal-infant ART prophylaxis has not been as steep as predicted, and efforts will not meet the World Health Organization goal to eliminate mother-to-child transmission by 2015. This slow decline in infant HIV-1 infections is partly due to suboptimal coverage at each step of the ART “prevention cascade” (Figure). Yet even if the goal of 90% ART coverage can be achieved, it is estimated that 138 000 infants will still become infected withHIV-1 annually1 because of several situations in which maternal ART prophylaxis is ineffective, including maternal late presentation for care, nonadherence, and acute maternal infection during breastfeeding. In low- and middle-income countries, only half of pregnant women attend therecommended4prenatal visits. Late initiation of ART results in high rates of mother-to-child transmission, with one South African study reporting a tripling of transmission rates in pregnant women who received less than 4 weeks of ART prior to delivery compared with women who received 16 to 32 weeks of treatment.2 Furthermore, a high number of women disengage from care after childbirth (Figure), leaving infants vulnerable to HIV-1 infection. Also of great concern is the increasing incidence ofHIV-1 infection in young women; an estimated 620 000 women aged 15 to 49 years from areas of high HIV-1 prevalence acquired HIV-1 in 2013. Acute HIV-1 infection among mothers accounts for up to 34%of mother-to-child transmission3 and will not be curbed by maternal ART-based strategies. Because of these established gaps in the prevention of mother-to-child transmission, there is a critical need to develop safe, feasible supplemental strategies to be used with the current ART-based strategies, such as a universal infant HIV-1 vaccine. Figure Maternal ART Coverage Goal and Currently Achieved ART Coverage in PMTCT High-Burden Countries

Amniocentesis for the detection of congenital toxoplasmosis: results from the nationwide Austrian prenatal screening program

Prenatal diagnosis of congenital toxoplasmosis (CT) influences therapeutical management in pregnant women and their offspring. In Austria, a nationwide serological healthcare program to identify potential maternal toxoplasma infections during pregnancy exists. We assessed the clinical use of amniocentesis for toxoplasma-specific polymerase chain reaction (PCR) on amniotic fluid to detect CT. Data on serology, amniocentesis, PCR, complications, treatment, and paediatric clinical outcome were collected retrospectively among the birth cohort 1992–2008. There were 1386 women with amniocentesis, but only in 707 cases (51%) was acute maternal infection confirmed serologically. A high proportion (49%) of amniocenteses with negative PCR results in women with chronic infection or seronegativity were performed without clinical justification for the women or their foetuses. The positive and negative predictive values of PCR were 94.4% and 99.3%, respectively. Thirty-nine foetuses with CT, including four deaths, were reported. The five PCR-negative but infected infants were identified by the serological and clinical follow-up program. Thirty percent of amniocenteses were performed in the third trimester, and gestational age or treatment did not influence PCR sensitivity. Amniocentesis is indicated in women with acute maternal infection, and facilitated targeted therapies in pregnant women and their offspring. In women with late toxoplasma infection, negative amniotic fluid PCR made treatment of infants unnecessary. Serological and clinical follow-up of infants is important to confirm the infection status of the infant. Recommendations, based on our 17-year experience, to improve the current diagnostic strategies and to reduce unnecessary amniocentesis, are given.

Survey of obstetrician-gynecologists in the United States about toxoplasmosis: 2012 update.

Toxoplasmosis, caused by the parasite Toxoplasma gondii, can have serious impacts on fetal development in the setting of acute maternal primary infection. The American College of Obstetricians and Gynecologists (ACOG) sought to determine current knowledge, practices, opinions, and educational preferences regarding T. gondii infection in pregnancy among ACOG members practicing prenatal care. ACOG sent a survey to 1,056 members chosen by stratified random sampling from membership lists, including 370 participants and 686 non-participants in the Collaborative Ambulatory Research Network (CARN). Mailings were sent up to four times to nonresponders. Survey minimum response rates were 40.3% (CARN) and 19.7% (non-CARN); response rates adjusted for imputed non-eligibility were 59.7% (CARN) and 22.6% (non-CARN). Among providers, 80.2% had diagnosed no acute maternal T. gondii infections in the past 5 years, 12.7% correctly identified the screening role of the Toxoplasma avidity test, 42.6% performed serologic T. gondii screening for at least some asymptomatic pregnant women, and 62.1% of those who so did used appropriate approaches. Providers in the northeastern United States were 2.02 times more likely to routinely screen than those in the west (p = 0.025) and female providers were 1.48 times more likely than male providers (p = 0.047). The potential educational interventions considered useful by the most practitioners were updated ACOG guidelines on screening (81.4%) and management (71.7%) for acute T. gondii infection in pregnancy. ACOG members would benefit from educational efforts targeted at risk factor counseling and screening approaches.

Acute Maternal Infection and Risk of Pre-Eclampsia: A Population-Based Case-Control Study

BackgroundInfection in pregnancy may be involved in the aetiology of pre-eclampsia. However, a clear association between acute maternal infection and pre-eclampsia has not been established. We assessed whether acute urinary tract infection, respiratory tract infection, and antibiotic drug prescriptions in pregnancy (a likely proxy for maternal infection) are associated with an increased risk of pre-eclampsia.Methods and FindingsWe used a matched nested case-control design and data from the UK General Practice Research Database to examine the association between maternal infection and pre-eclampsia. Primiparous women aged at least 13 years and registered with a participating practice between January 1987 and October 2007 were eligible for inclusion. We selected all cases of pre-eclampsia and a random sample of primiparous women without pre-eclampsia (controls). Cases (n = 1533) were individually matched with up to ten controls (n = 14236) on practice and year of delivery. We calculated odds ratios and 95% confidence intervals for pre-eclampsia comparing women exposed and unexposed to infection using multivariable conditional logistic regression. After adjusting for maternal age, pre-gestational hypertension, diabetes, renal disease and multifetal gestation, the odds of pre-eclampsia were increased in women prescribed antibiotic drugs (adjusted odds ratio 1.28;1.14–1.44) and in women with urinary tract infection (adjusted odds ratio 1.22;1.03–1.45). We found no association with maternal respiratory tract infection (adjusted odds ratio 0.91;0.72–1.16). Further adjustment for maternal smoking and pre-pregnancy body mass index made no difference to our findings.ConclusionsWomen who acquire a urinary infection during pregnancy, but not those who have a respiratory infection, are at an increased risk of pre-eclampsia. Maternal antibiotic prescriptions are also associated with an increased risk. Further research is required to elucidate the underlying mechanism of this association and to determine whether, among women who acquire infections in pregnancy, prompt treatment or prophylaxis against infection might reduce the risk of pre-eclampsia.