Congenital TORCH infections: Pathology review
Content Reviewers:Antonella Melani, MD
Contributors:Maria Emfietzoglou, MD, Evan Debevec-McKenney, Sam Gillespie, BSc, Jung Hee Lee, MScBMC
At the clinic, two mothers came in with their babies. The first baby is an 11 month old girl called Cecile, who is brought by her parents, who are immigrants, for a routine visit. You immediately noticed that she doesn’t react when you call her name, as if she can’t hear you at all. Upon eye examination, you find that Cecile has bilateral clouding of the lens. Then, upon cardiac auscultation, you hear a continuous rumbling murmur. Upon further questioning, Cecile’s mother tells you that, during the first trimester of pregnancy, she developed a rash that mainly involved her head and neck, as well as swollen lymph nodes behind the ears.
After Cecile, comes a 6 month old baby boy named Arthur with his mother, who is concerned because Arthur has developed multiple purple marks on his skin. Upon physical examination, you noticed that Arthur has an unusually large head for his age. Then, on fundoscopy, his eyes show white and yellow scars that look like cotton. You decide to order a CT scan of the brain, which reveals scattered calcifications. Upon further questioning, Arthur’s mother admits to handling her cat’s litter while she was pregnant, despite her doctor’s advice against it.
All right, now both Cecile and Arthur seem to have a congenital TORCH infection. TORCH is an acronym that stands for infections caused by Toxoplasma gondii; Other agents, such as syphilis, parvovirus B19, varicella zoster virus, and listeria; then there’s Rubella; Cytomegalovirus, and finally Herpes simplex virus-2 or HSV-2.
All these infections are lumped together because they can be vertically transmitted, which means that a pregnant individual can transmit the infection to their child either before birth via the placenta, or during and after birth via blood, body fluids, or breast milk.
Now, keep in mind that TORCH infections may share some non-specific signs and symptoms, including delayed growth, and hepatosplenomegaly or enlarged liver and spleen, which can lead to jaundice or yellow skin, and thrombocytopenia or low platelet count. So for your exams, it’s important that you’re able to distinguish the different TORCH infections based on additional characteristics.
Okay, the first TORCH infection is toxoplasmosis, which is caused by the protozoan parasite Toxoplasma gondii. For your exams, remember that pregnant individuals usually get infected from contact with cat feces, such as when handling cat litter, as well as consumption of undercooked meat, especially pork and lamb.
However, keep in mind that the pregnant individual typically remains asymptomatic, or may rarely develop lymphadenopathy or enlarged lymph nodes. The bad news is that toxoplasma can be transmitted to the fetus via the placenta, and if that happens during the first six months of pregnancy, it can lead to congenital toxoplasmosis.
Now, the most high yield manifestations of congenital toxoplasmosis include the classic triad of chorioretinitis, hydrocephalus, and intracranial calcifications. Chorioretinitis is an inflammation of the choroid and retina of the eye, which can be seen upon fundoscopy as white and yellow scars that look like cotton. Then, hydrocephalus is when fluid builds up within the ventricles, which are cavities within the brain. As a result, there’s enlargement of the ventricles, so these babies develop macrocephaly or an enlarged head.
Finally, intracranial calcifications are basically calcifications that are typically randomly distributed within the brain tissue, and can be seen on brain CT scan. An additional clue that you may find on a test question is that some babies with congenital toxoplasmosis may present with multiple purple-blue marks in the skin, which is often referred to as a “blueberry muffin” rash.
The next TORCH infections are Other agents, which includes syphilis, parvovirus B19, varicella zoster virus, and listeria. Now, syphilis is caused by the spirochete bacterium treponema pallidum, which is transmitted through sexual contact, including vaginal, anal, and oral sex.
Now, syphilis has three stages. The first stage as soon as the person gets infected is called primary syphilis or early localized stage, and it’s characterized by the presence of chancres or painless skin ulcers, which usually appear on the labia, anal region or cervix.
About 2 to 10 weeks later begins the second stage, which is called secondary syphilis, or the dissemination stage, where treponema pallidum enters the bloodstream. As a result, individuals develop generalized lymphadenopathy. In addition, individuals may present with a maculopapular rash, which are small bumps that start on the trunk and spread out to the arms and legs and eventually to the palms, soles, genitalia, and other mucous membranes.
And some individuals may also develop condyloma lata, which are smooth, white, painless, wart-like lesions on the genitals and around the anal region. The third stage is called latent syphilis, and it’s when the disease enters a dormant or asymptomatic phase. Individuals who don’t get any treatment eventually progress into the final stage of syphilis, which is called tertiary syphilis.
Here, the immune cells start to huddle around and form characteristic granulomatous lesions called gummas. In addition, various organs get damaged, especially the heart and blood vessels leading to cardiovascular syphilis, as well as the brain and spinal cord leading to neurosyphilis. What’s really important to remember is that the first and second stages are the most infectious, so that’s when the fetus is most likely to get infected, either via the placenta or during childbirth.
Now, congenital syphilis often results in hydrops fetalis, which is when the fetus has an abnormal accumulation of fluid in soft tissues. This poses a great risk for still-birth, which is when the fetus dies within the womb. Babies who survive the pregnancy typically develop some characteristic features that can be divided into early signs, which appear during the first two years of life; and late signs, which appear after the child is two years old. Early signs can include a maculopapular rash involving palms and soles of the feet, as well as snuffles or increased nasal secretions, which are laden with treponema.
On the other hand, late signs include frontal bossing where the forehead is really prominent, as well as a saddle nose with a depressed nasal bridge, and a short maxilla. Another very characteristic finding is Hutchinson teeth, which are small, notched, and widely spaced permanent teeth. These children may also develop saber shins, which refers to bending of the shinbone or tibia. Finally, congenital syphilis may lead to progessive damage to the vestibulocochlear nerve or cranial nerve VIII, which normally transmits sound. As a result, congenital syphilis may cause deafness or hearing loss.
Next up is parvovirus B19 infection, which is primarily transmitted via respiratory droplets when someone coughs or sneezes. In a pregnant individual, parvovirus B19 infection causes arthritis or joint inflammation with pain and stiffness. This usually affects the small joints of the hands, wrists, knees, and feet, and is often symmetrical, meaning that the same joints on both sides of the body will be affected. Now, this presentation is very similar to that of rheumatoid arthritis, so to set these two apart, remember that parvovirus B19 also leads to a decreased red blood cell production in the bone marrow, which can result in pure red blood cell aplasia. This is a type of anemia characterized by the absence of reticulocytes, which are red blood cell precursors in the bone marrow.
Now, parvovirus B19 can also be transmitted by a pregnant individual to the fetus via the placenta. As a result, the fetus will also develop anemia. Because there are fewer red blood cells to carry oxygen, the heart will pump a larger volume of blood to give the growing fetus all the oxygen it needs. This raises the pressure inside the fetal blood vessels, and fluid may start to leak out. This can ultimately result in hydrops fetalis, which poses a great risk for spontaneous abortion or still-birth, especially if the infection occurs in the first half of the pregnancy. The good news is that fetuses who survive the infection don’t develop any permanent defects or malformations.
Okay, moving onto the next one. Varicella or chickenpox is caused by the varicella zoster virus, or VZV for short. VZV can be transmitted by respiratory droplets when someone coughs or sneezes, as well as via contact with the oral or skin lesions of an infected person.
What can be concerning is when the VZV infection is transmitted to a pregnant individual who is unvaccinated or has no history of previous infection. Maternal varicella zoster usually causes a fever, headache, and overall weakness. After a couple days, the pregnant individual will develop an intensely pruritic, vesicular rash, which starts on the trunk and then spreads outward, eventually covering the entire body.
And most importantly, the pregnant person can transmit the infection to the fetus via the placenta. The main issue is when this occurs in the first or second trimester, when the fetus is still undergoing major development and is most vulnerable. This can lead to congenital varicella syndrome, where babies are born underdeveloped, and the most high yield findings include low birth weight, limb atrophy, and microcephaly or an abnormally small head. In addition, these babies may develop eye defects, such as cataracts, which refers to clouding or opacification of the lens, as well as neurological defects like cortical atrophy or brain degeneration, and intellectual disability.
Next up is listeria infection, caused by the bacteria listeria monocytogenes. In a test question, look for an individual that gets infected after ingestion of contaminated foods like unpasteurized dairy products and deli meats. Now, in pregnant individuals, listeria infection may cause fever, fatigue, and gastroenteritis with diarrhea, vomiting, and abdominal cramps. Another high yield presentation is amnionitis or infection of the amniotic fluid. And the most severe cases may even develop sepsis, which is when listeria spreads to the bloodstream.
Now, the main route of transmission to the fetus is via the placenta, which may result in spontaneous abortion or still-birth. If the fetus survives to term, it may develop sepsis and meningitis, which is an inflammation of the meninges that cover and protect the brain and spinal cord, and is fatal if untreated.
- "Robbins Basic Pathology" Elsevier (2017)
- "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
- "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
- "TORCH Infections" Clinics in Perinatology (2015)
- "TORCH (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus) screening of small for gestational age and intrauterine growth restricted neonates: efficacy study in a single institute in Korea" Korean Journal of Pediatrics (2018)