Today we're going to be talking about a specific virus, herpes simplex virus type 2, or HSV-2, that is best known for causing symptomatic genital infection in about 10% of sexually active individuals. What's less appreciated is that this virus is responsible for causing lifelong, often clinically silent infection, in about 20 to 30% of adults. If this silent infection is present in a pregnant woman, she can inadvertently infect her baby at the time of delivery with potentially devastating consequences. This newborn boy named Jack arrived 11 months after his parents were married. His mother, Carey, had enjoyed a healthy pregnancy and the delivery had gone smoothly. Except for the fact that Carey's obstetrician needed to perform a low forceps delivery when the infant's heart rate fell during the final stages of birth. Other than a few small abrasions on Jack's scalp where the forceps had made contact with his skin, Jack appeared to be a perfectly healthy baby boy. And the happy parents were able to bring him home within 48 hours of delivery. At five days of age, Carey brought Jack to their new pediatrician's office for a well-child visit. A fourth-year medical student, who was doing his pediatrics rotation at the clinic that month, was given the task of performing a preliminary assessment of baby Jack. During the physical exam, the medical student noticed some small blisters on the baby's scalp in the same areas where the forceps had caused minor trauma to the newborn's skin. In his physical exam notes, the medical student wrote vesicular rash on scalp, query herpes. During the pediatrician's examination of baby Jack, he also noticed the skin lesions on the baby's scalp. But he suspected that this was a hospital-acquired bacterial infection like bullous impetigo caused by Staphylococcus aureus. He instructed the medical student to send a sample of fluid from inside the blisters to the microbiology lab for gram stain and culture. After two days, the results came back negative for bacterial infection. Carey was notified by phone and she reported that Jack's rash seemed to have resolved and that he was doing well. Then three weeks later, Jack suffered a grand mal seizure, and his parents rushed him to the emergency room. The Physician who examined Jack had no access to the medical records from his first well-child visit. After a thorough examination and an EEG, no identifiable cause could be found to explain the seizure. So the medical team came to the conclusion that this must have been a febrile seizure, despite the fact that Jack's temperature wasn't elevated at the time of his seizure. After Jack had a second seizure that night, the infant was started on an anti-epileptic drug and discharged after 48 hours of being seizure free on the medication. At 2 months of age, Carey brought her son back to the pediatrician who had examined him in the On the day of his first seizure. Carey had noticed small, fluid-filled blisters on Jack's scalp again, in the exact same location as the rash he'd had when he was just a few days old. The pediatrician unroofed the blisters and sent the fluid for bacterial and viral cultures and a PCR test for herpes. The viral culture and PCR returned positive for herpes simplex type 2 and confirmed the diagnosis of neonatal herpes. The herpes simplex viruses are categorized into two types. HSV-1 most commonly causes sores around the mouth and lips, sometimes called fever blisters, or cold sores. While HSV-2 is the most common cause of genital herpes. Like the general population, between 20 to 30% of pregnant women are infected with the HSV-2 virus. And the majority are symptom free and may not even know they're carrying the virus. Carey was one of these individuals. HSV-2 can be transmitted in two ways. Firstly, it can be transmitted horizontally between sexual partners, most commonly by direct contact with the genitals of an infected individual. And secondly, the virus can also be transmitted vertically from an infected mother to her infant. And this usually occurs when the infant comes into contact with the virus during passage through the birth canal. The HSV-2 preferentially infects epithelial cells located in the mucosa or at sites of abrasion on the skin. Following entry and colonization of the skin or mucosa, the virus has evolved to exploit the cell biology of local neurons. The virus enters and travels up neuronal axons to local sensory ganglia in the peripheral nervous system. Where it begins to establish latency in the ganglia before returning back to the site of initial inoculation. There the virus replicates, causing cell death and the development of the small blisters that characterize herpes simplex infection. But in many cases, the symptoms can be so mild that they may go unnoticed. During the latent state in the sensory ganglia, HSV is kept in check by the adaptive immune system. Which tolerates the presence of the virus in the immune privileged tissues of the nervous system. The delicate balance needed to maintain the virus in its latent state depends on a well-functioning immune system with ongoing immune surveillance. When the immune system is weakened, the virus can reactivate and cause symptoms in the infected adults. But when a newborn like baby Jack is infected with the virus, the newborn's immune system is too naive to control the infection in the first place. After entering the body, the virus can disseminate to many organs, including the central nervous system, causing encephalitis. An infection of the brain that can lead to serious symptoms like seizures, irreversible neurological damage, and death. In Jack's case, if his HSV infection had been correctly diagnosed at the first well-child checkup, he could've received treatment with an antiviral medication that would have prevented unchecked viral replication and the associated neurological damage. Because the diagnosis of neonatal herpes was missed, Jack began showing early signs of neurological damage. And Carey was told that he would likely suffer from serious intellectual disability. In this case, the family decided to take legal action. Newborns are at greatest risk of vertical infection with HSV-2 when the mother acquires the virus for the first time late in the pregnancy. This is partly because the mother's immune system doesn't have time to make antibodies to the virus that could protect the newborn from infection at the time of delivery. Women with visible genital HSV-2 lesions at the time of delivery are usually delivered by cesarean section before the rupture of the membranes, to reduce the risk of infecting the newborn. However, since the majority of infected pregnant women have no history of symptoms or very mild symptoms, HSV-2 is often not suspected.
