COL4A1-related disorder as a mimic of congenital TORCHES infection-Expanding the clinical, neuroimaging and genotype spectrum.

Pseudo-TORCH Syndrome (PTS) encompasses a heterogeneous group of genetic disorders that may clinically and radiologically resemble congenital TORCH infections. These mimickers present with overlapping features manifested as intracranial and systemic abnormalities. Collagen type IV alpha 1 chain (COL4A1)-related diseases, characterized by autosomal dominant inheritance, exhibit a diverse phenotypic spectrum involving cerebrovascular, renal, ophthalmological, cardiac, and muscular abnormalities. Cerebrovascular manifestations range from small-vessel brain disease to large vessel abnormalities, resulting in intracerebral hemorrhage, periventricular leukoencephalopathy, and ventriculomegaly. Additional features include cortical malformations, eye defects, arrhythmias, renal disease, muscular abnormalities, and hematological manifestations. Age of onset varies widely, and phenotypic variability exists even among individuals with the same variant. In this study, we present two cases of COL4A1-related disorder mimicking congenital TORCH infections, highlighting the importance of recognizing genetic mimics in clinical practice.

Fetal Zika virus inoculation in macaques revealed control of the fetal viral load during pregnancy.

BACKGROUND: Early pregnancy Zika virus (ZIKV) infection is associated with major brain damage in fetuses, leading to microcephaly in 0.6-5.0% of cases, but the underlying mechanisms remain largely unknown. METHODS: To understand the kinetics of ZIKV infection during fetal development in a nonhuman primate model, four cynomolgus macaque fetuses were exposed in utero through echo-guided intramuscular inoculation with 103 PFU of ZIKV at 70-80 days of gestation, 2 controls were mock inoculated. Clinical, immuno-virological and ultrasound imaging follow-ups of the mother/fetus pairs were performed until autopsy after cesarean section 1 or 2 months after exposure (n = 3 per group). RESULTS: ZIKV was transmitted from the fetus to the mother and then replicate in the peripheral blood of the mother from week 1 to 4 postexposure. Infected fetal brains tended to be smaller than those of controls, but not the femur lengths. High level of viral RNA ws found after the first month in brain tissues and placenta. Thereafter, there was partial control of the virus in the fetus, resulting in a decreased number of infected tissue sections and a decreased viral load. Immune cellular and humoral responses were effectively induced. CONCLUSIONS: ZIKV infection during the second trimester of gestation induces short-term brain injury, and although viral genomes persist in tissues, most of the virus is cleared before delivery.

Discordant Zika Virus Findings in Twin Pregnancies Complicated by Antenatal Zika Virus Exposure: A Prospective Cohort.

BACKGROUND: There are limited data on the natural history of antenatal Zika virus (ZIKV) exposure in twin pregnancies, especially regarding intertwin concordance of prenatal, placental, and infant outcomes. METHODS: This prospective cohort study included twin pregnancies referred to a single institution from September 2015 to June 2016 with maternal ZIKV. Polymerase chain reaction (PCR) testing of maternal, placental, and neonatal samples was performed. Prenatal ultrasounds were completed for each twin, and histomorphologic analysis was performed for each placenta. Abnormal neonatal outcome was defined as abnormal exam and/or abnormal imaging. Two- to three-year follow-up of infants included physical exams, neuroimaging, and Bayley-III developmental assessment. RESULTS: Among 244 pregnancies, 4 twin gestations without coinfection were identified. Zika virus infection occurred at 16-33 weeks gestation. Zika virus PCR testing revealed discordance between dichorionic twins, between placentas in a dichorionic pair, between portions of a monochorionic placenta, and between a neonate and its associated placenta. Of the 8 infants, 3 (38%) had an abnormal neonatal outcome. Of 6 infants with long-term follow-up, 3 (50%) have demonstrated ZIKV-related abnormalities. CONCLUSIONS: Neonatal PCR testing, placental findings, and infant outcomes can be discordant between co-twins with antenatal ZIKV exposure. These findings demonstrate that each twin should be evaluated independently for vertical transmission.

The Role of Amniocentesis in the Diagnosis of Congenital Zika Syndrome.

There are limited data on amniocentesis as a diagnostic tool for congenital Zika syndrome. Here we report on a prospective cohort of 16 women with suspected Zika virus infection in a highly endemic area, and discuss the role of amniocentesis in the prenatal diagnosis of fetal Zika infection.

TORCH (Toxoplasmosis, Other, Rubella, Cytomegalovirus, Herpes Simplex Virus) Infection and the Enigma of Anomalous Fetal Development: Pregnancy Puzzles.

The cytomegalovirus (CMV), a common DNA virus with a high global seroprevalence, is the primary cause of teratogenic congenital infections, which presents a serious risk to public health. Maternal CMV infection is linked to congenital CMV (cCMV), a major contributor to non-genetic sensorineural hearing loss, cognitive developmental impairments, and cerebral palsy in infants. Transmission might occur through direct contact with infected bodily fluids, with higher transmission rates after primary infection and an increased risk of severe fetal effects before 20 weeks. The mother and fetus do not get immunity from a prior infection. Fetal growth restriction, fetal loss, and cerebral or extra-cerebral abnormalities that can be detected by ultrasonography are possible presentations of cCMV. Specific antibody detection or seroconversion is required for the diagnosis of maternal CMV during pregnancy. Amniocentesis is used to diagnose fetal CMV during pregnancy after eight weeks of presumed maternal infection and 17 weeks of gestation. The main preventive measure is hygiene education, as the effectiveness of immunoglobulins, antiviral medications, and vaccines is still up for debate. The focus is particularly directed toward the anomalous fetal outcomes observed during the course of the pregnancy.

A Rare Case of a Subgaleal Hematoma With Global Developmental Delay, Scurvy, and Congenital Toxoplasmosis, Rubella, Cytomegalovirus, Herpes Simplex, and HIV (TORCH) Infection.

This case report details the complex presentation of a six-year-old female child with global developmental delay (GDD), scurvy, congenital toxoplasmosis, rubella, cytomegalovirus, herpes simplex, and HIV (TORCH) infection and a subgaleal hematoma. The patient's medical history included delayed developmental milestones, bilateral congenital cataract, and a previous generalized tonic-clonic seizure. Thorough investigations revealed cerebral atrophy, bilateral ventricular dilatation, and periosteal thinning consistent with scurvy. The interdisciplinary approach involving neurology, ophthalmology, and orthopedics resolved the subgaleal hematoma. This case underscores the intricate interplay of neurological, nutritional, and infectious factors in pediatric conditions and highlights the importance of a collaborative, multidisciplinary approach for accurate diagnosis and effective management.

A Cross-Sectional Survey of Pediatric Infectious Disease Physicians' Approach to Congenital Cytomegalovirus Infection.

Congenital cytomegalovirus (cCMV) continues to be a major public health care issue due to its high prevalence throughout the world. However, there is a paucity of studies evaluating how providers manage this infection. This study surveyed North American Pediatric Infectious Disease (PID) physicians to elicit their approach towards the evaluation and treatment of this condition. Thirty-two PID physicians responded to this survey. Institutional testing and screening for cCMV were infrequently reported. The respondents in general agreed upon most laboratory and diagnostic testing except for neuroimaging. For those tests, there was a disparity in indications for head ultrasound versus brain MRI imaging. Most (68.8%) agreed with the clinical practice of starting valganciclovir in an infant less than 1 month of age with one sign or symptom of disease, and 62.5% would do so for an infant with isolated sensorineural hearing loss. However, only 28.1% would treat cCMV-infected infants older than 1 month of age. In conclusion, few healthcare institutions represented by PID physicians in this cohort had a cCMV screening or testing initiative, yet most respondents would test at a much higher level based on their clinical practice. While there is general consensus in evaluation and treatment of these children, there are disparities in practices regarding neuroimaging and indications for antiviral treatment with respect to age and severity of disease. There is a great need for an evidence based policy statement to standardize cCMV workup and treatment.

Analysis of an Expanded Targeted Early Cytomegalovirus Testing Program.

OBJECTIVE: Determine the detection rate from an expanded targeted early cytomegalovirus (CMV) testing program implemented from a large healthcare system (Intermountain Healthcare, IHC). STUDY DESIGN: Retrospective review. SETTING: Tertiary medical center. METHODS: An electronic system was modified to include indications for testing whenever a provider placed an order for CMV testing. A retrospective analysis of this database was performed. RESULTS: From March 1, 2021 to August 31, 2022, there were 3450 (8.8%) patients who underwent CMV testing out of 39,245 total live births within the IHC system. Since the formal implementation of this program in 2019, annual CMV testing has increased almost 10-fold: 2668 CMV tests were performed in 2021 compared to 289 CMV tests in 2015. The most frequent indication for congenital CMV (cCMV) testing was small for gestational age (SGA) (68.2%), followed by macrocephaly (13.5%), an abnormal hearing test (5.0%), and microcephaly (4.4%). Fourteen cCMV-infected infants were diagnosed all of them meeting the criteria for symptomatic cCMV. The most common indication resulting in a positive diagnosis was those who presented with SGA (n = 10 patients). The positivity rate would result in a prevalence of 35.7 symptomatic cCMV cases diagnosed per 100,000 live births, numbers comparable to those expected for universal cCMV screening. CONCLUSION: An expanded targeted early cCMV testing program may improve detection rates of symptomatic cCMV cases and should be considered as a feasible alternative approach to universal or hearing-targeted early CMV testing.

A predicting model of child-bearing-aged women' spontaneous abortion by co-infections of TORCH and reproductive tract.

To develop a predicting model of child-bearing-aged women' spontaneous abortion (SA) by co-infections of TORCH and reproductive tract, in order to provide a reference tool for accurately predicting the risk of SA and guide the early prevention, diagnosis and treatment of SA. A prospective cohort study was designed based on 218 958 child-bearing-aged women following up in Hebei province in China from 2010 to 2017. Multivariable logistic regression analysis was used to select candidate predictive variables. Fisher's discriminant analysis was performed to build a predictive model, and the validity of the model was evaluated. The incidence rate of SA was 2.4%. Multivariable logistic regression analysis showed that age (OR = 3.507), adverse pregnancy history (OR = 1.509), co-infections status of Candida and HBsAg (ORCandida positive×HBsAg negative  = 4.091, ORCandida negative×HBsAg positive  = 3.327, and ORCandida positive×HBsAg positive  = 13.762), and co-infections status of HBsAg, Rubella (IgG) and CMV (IgG) (ORHBs-Ag negative×Rubella (IgG) negative×CMV (IgG) positive  = 1.789, ORHBs-Ag positive×Rubella (IgG) positive×CMV (IgG) negative  = 3.809, and ORHBsAg positive×Rubella (IgG) positive×CMV (IgG) positive  = 11.919) were the independent predictors of SA. The total discriminant rate reached 91%, with 82% of the sensitivity and 91% of the specificity. The predicting model of child-bearing-aged women' SA by co-infections status has a good performance. The co-infection status of TORCH and reproductive tract are suggested to be considered in pre-pregnancy physical examination.

Seroprevalence of Toxoplasma, Rubella, CMV and HSV infection at a teaching hospital: A 7 year study from North India.

OBJECTIVES: The present study was aimed to find seroprevalence in different age group population to explore the burden of TORCH (toxoplasma, rubella virus, cytomegalovirus [(CMV] and herpes simplex virus [HSV]) infection in the North Indian Population. MATERIALS AND METHODS: It is a retrospective study carried out in the Microbiology Department, Institute of Medical Science, Banaras Hindu University (IMS, BHU), a tertiary care centre of North India. The blood samples of the suspected population of either sex or age group from different departments were analysed over a period of 7 years. The samples were tested for TORCH infections by the IgM ELISA kit following the manufactures instruction. RESULTS: Out of total 4044 samples, 1353 (33.46%) cases were seropositive with maximum cases from the obstetrics and gynaecology department 39.46%. The highest seropositivity of TORCH (43.15%) was in the age group 15-25 years followed by 36.33% in the age group 25-35 years. This study revealed an overall male and female ratio of the total positive cases as 0.12 while it was 2.2 for pediatric cases (0-15 years). The overall seroprevalence was contributed as toxoplasma 1.38%, rubella 1.14%, CMV 13.63% and herpes 17.43%. The overall seropositivity (IgM) contributed as toxoplasma gondii with 4%, rubella with 3%, cytomegalovirus with 41% and herpes simplex virus with 52%. The coinfection of HSV with CMV was most abundant with 246 cases. CONCLUSIONS: The seropositivity of toxoplasma and rubella were comparatively more in infants while CMV and herpes were more prevalent in adults. Though, the incidence of TORCH has reduced over the past few years. Furthermore, knowing the epidemiology is an important aspect to develop strategies and appropriate implementation for the prevention of infection.

SARS-CoV-2: Is it the newest spark in the TORCH?

Amid the rapidly evolving global coronavirus disease 2019 (COVID-19) pandemic that has already had profound effects on public health and medical infrastructure globally, many questions remain about its impact on child health. The unique needs of neonates and children, and their role in the spread of the virus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) should be included in preparedness and response plans. Fetuses and newborn infants may be uniquely vulnerable to the damaging consequences of congenitally- or perinatally-acquired SARS-CoV-2 infection, but data are limited about outcomes of COVID-19 disease during pregnancy. Therefore, information on illnesses associated with other highly pathogenic coronaviruses (i.e., severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome [MERS]), as well as comparisons to common congenital infections, such as cytomegalovirus (CMV), are warranted. Research regarding the potential routes of acquisition of SARS-CoV-2 infection in the prenatal and perinatal setting is of a high public health priority. Vaccines targeting women of reproductive age, and in particular pregnant patients, should be evaluated in clinical trials and should include the endpoints of neonatal infection and disease.

Pneumonia.

Neonatal pneumonia may occur in isolation or as one component of a larger infectious process. Bacteria, viruses, fungi, and parasites are all potential causes of neonatal pneumonia, and may be transmitted vertically from the mother or acquired from the postnatal environment. The patient's age at the time of disease onset may help narrow the differential diagnosis, as different pathogens are associated with congenital, early-onset, and late-onset pneumonia. Supportive care and rationally selected antimicrobial therapy are the mainstays of treatment for neonatal pneumonia. The challenges involved in microbiological testing of the lower airways may prevent definitive identification of a causative organism. In this case, secondary data must guide selection of empiric therapy, and the response to treatment must be closely monitored.

Diffuse periventricular calcification and brain atrophy: A case of neonatal central nervous system cytomegalovirus infection.

TORCH refers to the most common congenitally acquired infections: toxoplasma, rubella, cytomegalovirus, and herpes simplex virus. Neonatal cytomegalovirus infection remains a common cause of congenital infection worldwide with effects ranging from hearing impairment to significant neurological morbidity. We report a case of a term neonate with ventriculomegaly on prenatal ultrasound who presented with low birth weight, small head circumference, hepatosplenomegaly, and purpuric rash on physical exam. Central nervous system cytomegalovirus infection typically shows periventricular calcifications and associated deep white matter damage and ventriculomegaly. Ultrasound, computed tomography, and magnetic resonance imaging have different roles in the diagnosis of congenital central nervous system cytomegalovirus infection. Many imaging features of congenital cytomegalovirus are distinctive, and can spur a diagnostic work-up as well as help provide a prognosis.

Development of a novel, guinea pig-specific IFN-γ ELISPOT assay and characterization of guinea pig cytomegalovirus GP83-specific cellular immune responses following immunization with a modified vaccinia virus Ankara (MVA)-vectored GP83 vaccine.

The guinea pig (Cavia porcellus) provides a useful animal model for studying the pathogenesis of many infectious diseases, and for preclinical evaluation of vaccines. However, guinea pig models are limited by the lack of immunological reagents required for characterization and quantification of antigen-specific T cell responses. To address this deficiency, an enzyme-linked immunospot (ELISPOT) assay for guinea pig interferon (IFN)-γ was developed to measure antigen/epitope-specific T cell responses to guinea pig cytomegalovirus (GPCMV) vaccines. Using splenocytes harvested from animals vaccinated with a modified vaccinia virus Ankara (MVA) vector encoding the GPCMV GP83 (homolog of human CMV pp65 [gpUL83]) protein, we were able to enumerate and map antigen-specific responses, both in vaccinated as well as GPCMV-infected animals, using a panel of GP83-specific peptides. Several potential immunodominant GP83-specific peptides were identified, including one epitope, LGIVHFFDN, that was noted in all guinea pigs that had a detectable CD8+ response to GP83. Development of a guinea pig IFN-γ ELISPOT should be useful in characterization of additional T cell-specific responses to GPCMV, as well as other pathogens. This information in turn can help focus future experimental evaluation of immunization strategies, both for GPCMV as well as for other vaccine-preventable illnesses studied in the guinea pig model.

Analysis of TORCH infection in Qujing area / 国际检验医学杂志

Objective To analyze the detection results of TORCH antibodies for further understanding the TORCH infection situation among different groups in Qujing area .Methods The detection results of 3035 cases of TORCH antibodies were retro-spectively analyzed ,and the detection results were grouped into the male group and female group ,juvenile group and adult group , and the positive rate of TORCH antibodies was statistically analyzed .Results (1) In the TORCH-IgG various antibodies detec-tion ,the positive rate of CMV-IgG antibody was highest(84 .78% ) .In the TORCH-IgM various antibodies detection ,the positive rate of RUV-IgM antibody was highest(9 .92% ) .(2)The positive rates of RUV ,CMV and HSVⅠ /Ⅱ-IgG and IgM antibodies in the female group were higher than those in the male group ,and the differences were statistically significant (P0 .05) .(3)The positive rates of TOX ,RUV , CMV and HSVⅠ /Ⅱ-IgG antibodies in the adult group were higher than those in the juvenile group ,the differences were statistical-ly significant (P0 .05) .Conclusion The infection rates of CMV ,RUV ,HSVⅠ /Ⅲ were higher in Qu-jing area .The infection rates are higher in the adult group and female group .Therefore ,TORCH infection should be early found and the infected persons should take some intervention and treatment measures .

Epidemiological investigation on TORCH infection of children in Pu′er / 国际检验医学杂志

Objective To make an epidemiological investigation on TORCH infection in children in Pu′er city of Yunnan prov‐ince ,in order to provide references for the prevention and treatment of TORCH infection in children .Methods A total of 1 194 children treated at this hospital from January to December 2014 were selected and divided into five age groups .Serum TORCH spe‐cific IgM and IgG antibodies were detected by using enzyme‐linked immunosorbent assay(ELISA) and the positive rate of TORCH specific antibody and TORCH infection rate were comparatively analysed .Results The positive rate of TORCH specific IgM anti‐body was significantly lower than that of IgG .The range of positive rate of IgM was 0 .00% -3 .10% ,and that of IgG was 10 .13% -82 .24% .The total infection rate of TORCH was 96 .98% .There were no significant differences in the infection rate of single item of TORCH or the total TORCH infection rate among the five different age groups(P>0 .05) .The distribution of infec‐tion rate of single item of TORCH among the five age groups was statistically significantly different(P0 .05) .Conclusion Children with TORCH infection in this area mainly are infected by CMV ,followed with RV and HSV infections ,while TOX infection is uncommon .There are no obvious differences in different seasons and children in different age groups .

Ultrasound and serological diagnosis of TORCH infection in pregnant women / 国际检验医学杂志

Objective To study the use of ultrasound and serological diagnosis of TORCH infection in pregnant women .Methods Enzyme linked immunosorbent assay of serum IgM antibodies specific for TORCH were performed .Biweekly ultrasonic inspec‐tion were also performed to detect fetal development .Results Among 656 cases of pregnant women ,the TORCH infection rate was 19 .36% ,and the positive rates of IgM specific for toxoplasma ,Rubella virus ,cytomegalovirus ,herpes simplex virus were 3 .50% , 2 .13% ,4 .27% and 4 .72% .Among TORCH antibody positive pregnant women ,ultrasound abnormality included 37 cases of omphalocele ,12 cases of cervical lymph hydrocyst ,4 cases of growth‐stopping ,6 cases of hydrocephalus ,9 cases of fetal death ,16 cases of single umbilical artery hydronephrosis ,12 cases of gastroschisis ,24 cases of intrauterine fetal growth retardation ,and the total abnormal rate was 18 .29% .Among 656 cases of pregnant women ,there are 574 cases of normal deliveries ,including 56 cases of TORCH infection ,accounting for 9 .76% ,and 82 cases with adverse pregnancy outcome ,including 43 cases of TORCH infection , accounting for 52 .44% ,which was higher than that in pregnant women with normal deliveries(P<0 .05) .Conclusion Ultrasound and serological diagnosis of TORCH infection could be reliable and effectively improve the quality of the population .