Ocular Involvement in Congenital Infections - TORCH. / Augenbeteiligung bei kongenitalen Infektionen ­ TORCH.

This review summarises the ophthalmological findings in congenital infections. Intrauterine infections are an important cause of childhood blindness. The most common infections are grouped under the acronym TORCH, which stands for Toxoplasma gondii, others, rubella, CMV, and herpes simplex. Overall, these infections are not very common in first-world countries during pregnancy, but are of particular importance because of the threat to vision. Diagnosis of infection or reactivation is a gynaecological challenge. However, ophthalmological examination of newborns can be appropriately targeted if the causative agent is known. The most important therapeutic agents used in the newborn are summarised.

Fetal and neonatal abnormalities due to congenital herpes simplex virus infection: a literature review.

OBJECTIVE: Herpes simplex virus (HSV) infection during pregnancy can cause severe neonatal infections. It is also a rare cause of congenital infections. We aimed to describe fetal and neonatal abnormalities of congenital HSV infection in order to define the features that are accessible to prenatal diagnosis during ultrasound screening and/or during a work-up for congenital malformations. METHODS: We analysed all cases of congenital HSV infection (CHI) described before and/or after birth and identified in Pubed and classified the findings as accessible or not to prenatal diagnosis. RESULTS: Thirty-six cases of congenital herpes infection were reported, of which 15 were described prenatally and 21 postnatally. The most frequently reported malformations accessible to prenatal diagnosis were cerebral anomalies. The most common abnormalities described after birth were skin lesions and keratitis, which are not considered amenable to prenatal ultrasound detection. CHI can due to either HSV1 or HSV2 infection, whether primary or non-primary infection, with or without the presence of maternal symptoms. CONCLUSION: Prenatal ultrasound abnormalities due to CHI are rare, varied and non-specific. There is no clear role for fetal ultrasound in the routine management of women with primary or non-primary HSV infection in pregnancy. However, in fetuses with ultrasound abnormalities suggestive of congenital infection, HSV should still be considered as a differential diagnosis after the more common in utero infections, such as cytomegalovirus, are excluded.

Congenital cytomegalic inclusion disease with disseminated Herpes simplex infection.

We report a case of congenital cytomegalovirus and Herpes simplex virus infection suspected via ultrasound indicated by the presence of fetal cerebral abnormalities. The pregnancy was electively terminated at 31 weeks of gestation. The postmortem examination of the foetus showed brain with lissencephaly. The histopathological examination revealed numerous enlarged cells containing cytomegalic inclusions and multinucleated giant cells in multiple fetal organs and placenta. Documented evidence of histopathological detection of cytomegalovirus inclusions in multiple organs are very sparse in literature. This case highlights the causal relationship of viral infections in early pregnancy and abnormalities of the central nervous system.

Prevalence of a positive TORCH and parvovirus B19 screening in pregnancies complicated by polyhydramnios.

OBJECTIVE: The aim of this study was to evaluate the rate of women with polyhydramnios who eventually screened positive to infectious disease by serum screening testing for TORCH and parvovirus B19. METHODS: This is a retrospective observational study on singleton pregnancies with a diagnosis of polyhydramnios and who had serum screening for TORCH and parvovirus B19. Patients were followed with serial ultrasounds between 2006 and 2013. Maternal characteristics, medical and obstetric history were reviewed. Ultrasound parameters, including amniotic fluid index and fetal anomalies, and the results of serologic tests were reviewed. RESULTS: Two hundred ninety patients met the inclusion criteria. Of these, 56 (19%) presented one of the following pathological conditions associated with polyhydramnios: diabetes (13% of total cases), obstructive gastrointestinal lesions (5%), Rhesus isoimmunization (0.3%), chromosomal abnormalities or genetic syndromes (1%). Among the remaining 234 patients, only three had a positive test result for infectious disease (1%, 95% Confidence Interval (CI) 0-4%): two women were positive for parvovirus B19 and one for toxoplasmosis infection. In none of them the fetus was affected, as confirmed by serum testing after birth and by 3 years follow-up. CONCLUSIONS: Infectious disease screening does not seem beneficial in pregnancies with isolated polyhydramnios.

Premature newborns with fatal intrauterine herpes simplex virus-1 infection: first report of twins and review of the literature.

BACKGROUND: Neonates with blistering skin diseases are dermatologic emergencies. The pathologies involved can pose diagnostic difficulties and there exists a variety of potential life-threatening differential diagnoses. OBJECTIVE: description of the first case of intrauterine acquired herpes simplex virus (HSV) 1 infection in twins. METHODS: We present the case of two premature bicordial biamniotic twins (27th week of gestation) whose intrauterine growth retardation, fetal anaemia and cardiotocography abnormalities led to a caesarean emergency delivery. RESULTS: Accurate medical history revealed a maternal febrile gingivostomatitis at the 23rd week of gestation, which was neglected by the treating gynaecologist. Respiratory distress was present at delivery and intubation was necessary in both children. The whole skin showed extensive erosions and ulcerations and the mucosa of the eyes and genitals was also involved. Intrauterine Herpes simplex virus (HSV) 1 infection was confirmed by immunohistochemistry of skin Tzanck smear (HSV 1 positive, HSV 2 negative), real-time polymerase chain reaction of both serum and skin (HSV 1 positive; HSV 2 negative) and maternal serology positive for HSV 1 IgM and IgG. Siblings were immediately treated with high-dose endovenous acyclovir. Anaemia thrombocytopenia and hepatorenal values markedly deteriorated and both developed consequential hepatorenal failure. The third day live supportive measures were terminated after parental informed consent and both siblings deceased shortly after on their mother's breast. DISCUSSION: Intrauterine HSV infection is rare and accounts only for 5% of neonatal HSV infections. Literature reports only 64 cases and 90% of those are related to HSV-2. Transplacental viral transmission is highest during the first 20 weeks of gestation and has been observed in pregnant women with disseminated HSV infection. Mortality and morbidity of intrauterine herpetic infection are extremely high. CONCLUSION: Despite transplacental HSV transmission remains a rare event, the potential devastating outcome justifies immediate adequate antiviral treatment in a pregnant woman affected by primary HSV infection.

Australian Paediatric Surveillance Unit annual report, 2013.

This report provides an update on the surveillance conducted by the Australian Paediatric Surveillance Unit (APSU) during the period January to December 2013. The APSU facilitates national active surveillance of uncommon diseases of childhood including selected communicable diseases. This report includes data on the following conditions: acute flaccid paralysis (AFP), congenital cytomegalovirus (cCMV), congenital rubella, perinatal exposure to HIV and paediatric HIV infection, neonatal herpes simplex virus (HSV), congenital varicella, neonatal varicella, severe complications of varicella and juvenile onset recurrent respiratory papillomatosis (JoRRP). Surveillance of severe complications of influenza was undertaken during the influenza season (July to September 2013).

Systematic review on molecular detection of congenital and neonatal infections caused by TORCH and SARS-CoV-2 in newborns' cerebrospinal fluid.

OBJECTIVE: To verify the use and identify advantages of molecular methods for congenital infections diagnosis in cerebrospinal fluid of neonates. DATA SOURCE: The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO), under CRD42021274210. The literature search was performed in databases: PubMed, Virtual Health Library/ Latin American and Caribbean Center on Health Sciences Information (VHL/BIREME), Scopus, Web of Science, Excerpta Medica database (EMBASE), Cochrane, ProQuest, and EBSCOhost. The search was carried out from August to October 2021 and updated in December 2022, respecting the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The selection sequence was: 1) Duplicate title removal; 2) Examination of titles and abstracts; 3) Full-text retrieval of potentially relevant reports; and 4) Evaluation of the full text according to eligibility criteria by two independent authors. Inclusion criteria considered randomized and non-randomized control trials, longitudinal, cross-sectional, and peer-reviewed studies in humans, published in English, Spanish, Italian, and Portuguese, with newborns up to 28 days old who had congenital neuroinfections by toxoplasmosis, rubella, cytomegalovirus, herpes simplex (TORCH), and others such as Treponema pallidum, Zika, parvovirus B-19, varicella zoster, Epstein-Barr, and SARS-CoV2, diagnosed by polymerase chain reaction (PCR). Two evaluators extracted the following information: author, year of publication, nationality, subjects, study type, methods, results, and conclusion. DATA SYNTHESIS: The most studied pathogen was herpes simplex. Several articles reported only nonspecific initial symptoms, motivating the collection of cerebrospinal fluid and performing PCR for etiological investigation. CONCLUSIONS: Molecular methods are effective to detect pathogen genomes in cerebrospinal fluid, which can impact clinical evolution and neurological prognosis.

Significance of maternal screening for toxoplasmosis, rubella, cytomegalovirus and herpes simplex virus infection in cases of fetal growth restriction.

AIM: The objective of this study was to evaluate the significance of maternal toxoplasmosis, rubella, cytomegalovirus (CMV) and herpes simplex virus (TORCH) screening in cases of fetal growth restriction (FGR). MATERIAL AND METHODS: The medical records of women carrying fetuses with FGR who underwent TORCH screening over a 10-year period were retrospectively reviewed for maternal and congenital TORCH infection. Women carrying fetuses with FGR routinely underwent serologic TORCH tests and systematic ultrasound evaluation for congenital abnormalities. If a congenital CMV infection was suspected, amniotic fluid, placenta or neonatal urine was used for CMV DNA detection by polymerase chain reaction. RESULTS: In 319 patients, no cases of maternal or congenital infection with toxoplasma, rubella, or herpes simplex virus were found. Conversely, six cases (1.8%) were diagnosed with congenital CMV infection, two of which had no structural abnormalities other than FGR. CONCLUSIONS: A complete maternal TORCH screening for cases of FGR appears to be unnecessary. Although a maternal CMV test can be considered, the incidence of congenital CMV infection was found to be low in FGR cases.

Imaging of Congenital/Childhood Central Nervous System Infections.

This article highlights the changing profile of the pediatric patient with central nervous system infection as countries develop and the roles of different imaging modalities such as cranial ultrasound, MR imaging, and computed tomography. It discusses the commonly encountered congenital toxoplasmosis, rubella, cytomegalovirus, herpes simplex (TORCH) infections, Group B Streptococcal and Escherichia coli infections in the neonatal period, and disease outbreaks affecting children. Iatrogenic, opportunistic, and immune-mediated changes as well as long-term effects of infection and mimics of infection are also discussed. Variety of images is provided to show the range of neuroimaging findings encountered, particularly on cranial ultrasound and MR imaging.

Intrauterine herpes simplex virus infection presenting with hypopigmented lesions.

Genital herpes simplex virus (HSV) is a sexually transmitted infection that can be transmitted from mother to child in utero, perinatally, or postnatally. Cutaneous infection with HSV commonly presents as vesicles affecting the skin, eyes, or mouth. In our case, we report a well child with cutaneous hypopigmented patches at birth that preceded typical blistering.

Infections at the maternal-fetal interface: an overview of pathogenesis and defence.

Infections are a major threat to human reproductive health, and infections in pregnancy can cause prematurity or stillbirth, or can be vertically transmitted to the fetus leading to congenital infection and severe disease. The acronym 'TORCH' (Toxoplasma gondii, other, rubella virus, cytomegalovirus, herpes simplex virus) refers to pathogens directly associated with the development of congenital disease and includes diverse bacteria, viruses and parasites. The placenta restricts vertical transmission during pregnancy and has evolved robust mechanisms of microbial defence. However, microorganisms that cause congenital disease have likely evolved diverse mechanisms to bypass these defences. In this Review, we discuss how TORCH pathogens access the intra-amniotic space and overcome the placental defences that protect against microbial vertical transmission.

Congenital herpes simplex virus infection among hospitalized infants in Poland.

INTRODUCTION AND OBJECTIVE: Congenital herpes simplex virus infection (cHSV) is a rare entity and may pose a life-threatening disease for the newborns. Due to the public health and clinical importance of cHSV infection in infants, the recent data on this disease in Poland should be investigated. The aim of the study was to evaluate the incidence and other factors related to cHSV. MATERIAL AND METHODS: The study is retrospective, population-based that utilised the hospital discharge records of cHSV patients. Data were obtained from National Institute of Public Health NIH - National Research Institute in Warsaw, Poland, covering the period 2014-2019. RESULTS: The study group consisted of 1,573 cHSV newborns (841 males and 732 females). Among this group, 70.1% were infants up to 90 days of age and 3.6% were neonates up to 28 days of age. The mean and median age was 98 days (95% CI: 94.5-101.8, SD 74) and 70 days (IQR: 53-104), respectively. Based on the hospital registry the overall average cHSV incidence over the study period was estimated to be 69 per 100,000 live births. The number of cHSV infection fluctuated over the years 2014-2019 with a significant decreasing trend from 2015-2019 (P<0.01). A significantly higher cHSV incidence was observed among patients from urban than rural areas of Poland (88 vs 40/100,000 live births; P<0.001). CONCLUSIONS: CHSV incidence may be related to multifactorial conditions for the occurrence of this disease. Further studies on changes in the incidence of cHSV are needed.

A case of congenital herpes simplex virus infection diagnosed at 8 months of age.

We present the case of an 8-month-old boy with the repeated recurrence of vesicles from the time of birth and who subsequently manifested psychomotor developmental delay. We retrospectively diagnosed the patient with congenital herpes simplex virus (HSV) infection. Computed tomography showed multiple calcifications in the periventricular white matter and thalami. The bilateral deep white matter showed an abnormally high signal intensity on T2-weighted magnetic resonance imaging. The patient required consecutive, suppressive therapy with valacyclovir to prevent the repeated recurrence of vesicles. This case presented a milder phenotype of congenital HSV infection in comparison to previous reports, and highlights the importance of the careful examination for this disease when neonates present with skin lesions.

Congenital herpes simplex virus infection: two unique cutaneous presentations associated with probable intrauterine transmission.

Cutaneous manifestations of congenital herpes simplex virus (HSV) have been classically described as grouped vesicles on an erythematous base. We report two cases of HSV infection wherein both infants presented at birth with widespread erosions and an absence of vesicles or vesicopustules. The presence of skin lesions at birth, neurologic changes seen on radiographic imaging, and a cesarean section delivery in one case suggests intrauterine transmission in both neonates.

Guías Latinoamericanas de Infecciones Congénitas y Perinatales de la Sociedad Latinoamericana de Infectología Pediátrica (SLIPE). Parte II / Latin American Guidelines on Congenital and Perinatal Infections from the Latin-American Society of Pediatric Infectious Diseases (SLIPE). Part II

Las infecciones perinatales son una causa de morbilidad, tanto fetal como neonatal, y que compromete la salud de la mujer embarazada, por lo que su diagnóstico, tratamiento, e intento de eliminación son una prioridad en América Latina y el Caribe. Este documento representa la segunda entrega realizada por expertos en la región dentro de la Sociedad Latinoamericana de Infectología Pediátrica (SLIPE), brindando una mirada actualizada en el manejo de las infecciones congénitas y entrega herramientas para detectar posibles momentos estratégicos de intervención y cambio en el manejo de las infecciones congénitas.

Perinatal infections are a major cause of morbidity and mortality in the fetus, neonate, and the health of the pregnant woman. Diagnosis, treatment, and the search for elimination of these diseases are a priority in Latin America and the Caribbean. This document represents the second delivery by a group of experts in the region inside the Latin-American Society of Pediatric Infectious Diseases (SLIPE), presenting a up-to-date look into the management of congenital infectious diseases and give a tool to detect possible strategic sceneries and a change in the management of congenital infections in our region.

Eye manifestations of intrauterine infections and their impact on childhood blindness.

Intrauterine infections are important causes of childhood blindness in both developed and developing countries. Chorioretinal scars are the most characteristic eye manifestation of a congenital or prenatal infection. The various ocular manifestations of congenital infections, summarized by the mnemonic TORCH, and recent additions to the "other" category (lymphocytic choriomeningitis virus and West Nile virus) are discussed.

A systematic review of the incidence of sensorineural hearing loss in neonates exposed to Herpes simplex virus (HSV).

OBJECTIVE: To develop evidence-based guidelines for appropriate audiological monitoring of children born following exposure to or infection with Herpes simplex virus (HSV) for development of immediate or delayed-onset of sensorineural hearing loss (SNHL). DATA SOURCES: A Medline search of the 1966-July 2007 database was supplemented by search of the additional database Embase (1980-July 2007). Manual search was conducted of references of identified papers and book chapters. STUDY SELECTION: Articles were sought that were longitudinal in design, to include an inception cohort of children infected with (or exposed to) HSV who were entered at a similar point at birth and followed over time with serial audiometry to identify hearing loss if it developed. DATA EXTRACTION: Patient information and audiometric data extraction from relevant articles was performed independently by all three researchers. Discrepancies were resolved by mutual consensus. DATA SYNTHESIS: Data was analyzed using descriptive statistics. RESULTS: Three papers reported five children with SNHL following apparent disseminated HSV-2 infections in which other obvious clinical sequelae of HSV infection and co-morbid conditions were present. Audiometric information is lacking regarding onset and progression. There are no reports of delayed-onset SNHL following perinatal or asymptomatic HSV infection. CONCLUSIONS: The development of SNHL in children with exposure to HSV occurs rarely. Routine serological screening for HSV infection in otherwise healthy neonates newly diagnosed with SNHL is unjustified. There is insufficient data to define the incidence and natural history of SNHL in children with HSV infections. Carefully designed and conducted studies are needed to address this issue.

Prevalence of HSV1/2 Congenital Infection Assessed Through Genome Detection on Dried Blood Spot in Individuals with Autism Spectrum Disorders.

BACKGROUND/AIM: Etiopathogenesis of autism spectrum disorders (ASD) remains to be elucidated. Congenital infections, particularly viral infections, have repeatedly been associated with the onset of such disorders. Our study aimed at assessing the prevalence of herpes simplex type 1 and 2 (HSV1/2) congenital infections in patients with ASD. MATERIALS AND METHODS: In our case-control study, a total of 38 children with ASD were compared to 44 age- and sex-matched controls regarding the presence of HSV1/2 infection though viral DNA polymerase chain reaction performed on dried blood spots collected at birth. RESULTS: No HSV congenital infection was detected in either group. CONCLUSION: Our negative finding is in agreement with other studies that failed to demonstrate a definitive role of HSV on the onset of ASD. Further investigation of congenital HSV prevalence in larger and more powerful studies is needed to undeniably discard a role of such virus in the etiopathogenesis of ASD.