Elsevier

Survey of Ophthalmology

Volume 53, Issue 2, March–April 2008, Pages 95-111
Survey of Ophthalmology

Major Review
Eye Manifestations of Intrauterine Infections and Their Impact on Childhood Blindness

https://doi.org/10.1016/j.survophthal.2007.12.003Get rights and content

Abstract

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.

Introduction

The most common congenital intrauterine infections can be summarized by the mnemonic TORCH: Toxoplasma gondii, others, rubella, cytomegalovirus, and herpes simplex virus. “Others” includes treponema pallidum, varicella–zoster virus, Epstein–Barr virus, human immunodeficiency virus, lymphocytic choriomeningitis virus, and West Nile virus. These are a potential cause of preventable childhood blindness in all parts of the world.

These agents produce a relatively mild illness in the mother, compared to the impact in the developing fetus. More virulent agents result in a spontaneous abortion or stillbirth, although the named agents, if contracted early in the first trimester, may result in abortion or stillbirth as well. They are transmitted transplacentally, and have a direct toxic effect (inflammation and necrosis). Additionally, in the first trimester, when the fetus has immature, developing organs, there may be a teratogenic effect. If the fetus is unable to eliminate the organism, this may lead to chronic infection and, in some cases immune tolerance, and the diagnosis can be made by elevated levels of IgM and IgA antibodies.

In humans IgG is actively transported across the placenta. IgM is not. This placental transfer onsets at the 24th week of gestation and increases exponentially during the second half of pregnancy. The baby receives from the mother, pre-natally, IgG and post-natally (from colostrum and breast milk), mostly s IgA (secretory IgA) and small amounts of IgG and IgM (short half life of one to two days).13, 51, 90 After birth, the child's own production of IgM starts almost immediately, but the production of IgG does not start for almost 6 months. Therefore, in the first 6 months of life, elevated levels of IgG were mostly likely from transplacental transfer from the mother. Elevated levels of IgM antibodies in the mother support the congenital nature of the infection.

Section snippets

Agent and Epidemiology

Toxoplasma gondii derives from the Greek, toxon meaning bow (the shape of the proliferative form), and gondii, for a rodent (Ctenodactylus gundi) indigenous to North Africa from which the organism was first isolated.82 Toxoplasma gondii is an obligate intracellular parasite, which probably evolved from a unicellular alga because it has an organelle similar to a chloroplast. It has a life cycle that has three forms, an oocyst (found in the gut of cats), a tissue cyst, and an active, or

Agent and Epidemiology

The rubella virus is a member of the Togaviridae family in which the virus contains a single-stranded RNA surrounded by a lipid envelope, or “toga.” The congenital form was first described by an ophthalmologist, Sir Norman McAlister Gregg, in 1941. He practiced in Sydney, Australia, where he reported several cases of congenital cataracts, congenital heart disease, and deafness associated with rubella during pregnancy.41 This represents the first demonstration of teratogenicity secondary to a

Agent and Epidemiology

Cytomegalovirus is a member of the herpes virus group, and was first described in the late nineteenth century as a rare cause of “cytomegalic inclusion disease” of the fetus and newborn.47 It is the cause for the most common intrauterine infection, with reported rates ranging from 0.5% to 2.4% of live births.32 Infection is usually subclinical. The prevalence of latent infections in young adults varies with age and geography, increasing with age, and being more prevalent in developing countries.

Agent and Epidemiology

Herpes simplex virus (HSV) is a double-stranded DNA virus. HSV infections were first described by the Greeks, and Hippocrates used the word “herpes,” which means to creep or crawl to describe the spreading of the lesion.102 There are two types of Herpes simplex virus, HSV type 1 and type 2. HSV-1 is the oral strain, and is responsible for mouth lesions, eye infections, and encephalitis, whereas HSV-2 is the genital strain, and produces genital infection.34, 102 The latter is transmitted

Lymphocytic Choriomeningitis Virus

This agent is in the “other” category, but will be discussed more extensively because the authors feel it is greatly under-diagnosed due to lack of knowledge.

Agent and Epidemiology

West Nile virus (WNV) was first isolated from a febrile patient in the West Nile district of Uganda in 1937. From 1937 to the early 1990s, human outbreaks, manifesting as mild febrile illnesses, were rarely reported in Israel and Africa. Since 1996, there have been outbreaks involving thousands of people in Romania, Russia, Israel, and the United States and Canada. In the United States, it was first detected in 1999 in an outbreak of encephalitis in New York City. Since then the virus has

Agent and Epidemiology

Treponema pallidum belongs to the family Spirochaeteceae, the same family as that of Borrelia and Leptospira. It remains active in a specially enriched media for up to a week and does not grow on routine culture media. It is the causative agent of the sexually transmitted disease syphilis. This sexually transmitted disease has had a great impact on the course of civilization. The availability of penicillin after World War II was instrumental in the reduction in the incidence of this infection.

Transmission

Impact on Childhood Blindness

Childhood blindness makes an important contribution to the overall blindness in the world. Considering years of visual loss, the impact per patient is much greater if blindness onsets in childhood. The prevalence of childhood blindness is highest in the developing countries—Africa, with 1.1 per 1,000 children in the age range 0–15 years, followed by 0.9 per 1,000 in Asia. Different factors have been implicated in the etiology of childhood blindness, one of which operates in the intrauterine

Summary

The eye-related finding most characteristic of a prenatal, and therefore, congenital infection is a chorioretinal scar or an active chorioretinitis, as can be seen in congenital toxoplasmosis, cytomegalovirus, herpes simplex, lymphocytic choriomeningitis virus, varicella–zoster infections, and most recently WNV. Congenital cataracts are suggestive, but less specific for congenital infection. They may be a relatively isolated finding in rubella, syphilis, varicella–zoster, and Epstein–Barr virus

Method of Literature Search

An online search of the literature was conducted on Medline articles in all languages covering years from 1949 to 2006 with the keywords congenital, eye, systemic, toxoplasmosis, cytomegalovirus, herpes, rubella, West Nile virus, lymphocytic choriomeningitis. Well-documented individual patient reports and patient series of ocular manifestations of congenital infections in English literature were reviewed.

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      Congenital Epstein-Barr virus (EBV) has been reported associated with congenital cataract in some sporadic cases [33]. EBV causes a relatively mild illness in the mother and is transmitted transplacentally to the fetus, with both a direct toxic and a teratogenic effect [33]. In older children and adolescents, EBV infection presents with fever, fatigue, exudative pharyngitis, and posterior cervical lymphadenopathy.

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    The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this review. This article was supported in part by grants to Dr. Mets from the Guild Fund of the Children's Memorial Hospital and Research to Prevent Blindness (unrestricted grant), Chicago, Illinois, USA.

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