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Subclinical Herpes Simplex Virus in Neonates: What to Do?

Subclinical Herpes Simplex Virus in Neonates: What to Do? 1024 683 Katie Brind'Amour, PhD, MS, CHES

Neonates can test positive for HSV without having visible lesions or other classic symptoms, leaving clinical uncertainty regarding appropriate antiviral treatment and testing protocols.

Researchers at Nationwide Children’s Hospital have shared data on a sample of 17 neonates who tested positive for herpes simplex virus (HSV) at mucosal sites, without any mucosal lesions, positive blood or spinal fluid tests, or other obvious manifestations of neonatal HSV disease. Their HSV-positive status was only revealed due to the hospital’s standard practice of testing for HSV among all neonates evaluated for sepsis — a rare protocol at pediatric medical centers.

“Our molecular virology laboratory that does our HSV PCR [polymerase chain reaction] testing is wonderful — they run the tests every day, and we have results in a very timely manner,” says Pablo Sánchez, MD, principal investigator in the Center for Perinatal Research at the Abigail Wexner Research Institute and a board-certified neonatologist and pediatric infectious diseases specialist at Nationwide Children’s. He is senior author on the study, published in The Journal of Pediatrics.

“Many places around the country have to send the clinical specimens for HSV PCR testing to an off-site reference lab and results are not known for several days,” he says. “When you have a condition that requires treatment within 24 hours, that’s not very helpful.”

The urgency of initiating treatment leads many clinicians to start antiviral therapy with acyclovir in advance of known results — provided the infant has classic HSV symptoms or there was confirmed intrapartum HSV disease in the mother. However, in the absence of mucosal lesions, skin vesicles, liver disease, seizures or other typical signs of HSV infection or risk factors, empiric acyclovir treatment is unclear.

“As we started screening babies for HSV during standard sepsis evaluations, we found that some infants don’t really fit into those standard diagnostic categories,” says Dr. Sánchez.

Rachel Graf, MD, first author on the publication and now a pediatric resident at Rainbow Babies & Children’s Hospital, and the study team identified 17 subclinical cases among the 120 neonates with positive HSV tests since the start of an HSV surveillance study in 2001.

“What if you detect HSV from mucosal sites, but blood and cerebrospinal fluid are normal, as we found in these babies?” asks Dr. Sánchez. “How significant is that? Is it a false positive PCR test result, or maybe early detection prior to symptoms? What do you do?”

Dr. Sánchez hopes that the data from infants at Nationwide Children’s can spark discussion about managing this rather novel subset of patients with HSV. He believes a point-of-care test for neonatal HSV that combines pathogen detection with host immune response could revolutionize the ability to effectively identify the infection earlier and make better surveillance — and earlier treatment — possible.

At present, little is known about the true incidence of HSV infection in neonates, in part because of the difficulty many centers have with timely testing. Estimates range from 1 in every 3,000 to 1 in 20,000 live births. Left untreated, it can be deadly, and even with treatment, some babies sustain long-term neurodevelopmental delays, blindness and significant organ damage.

Dr. Sánchez has been tracking cases for decades, both at Nationwide Children’s and his prior appointments. He has periodically made attempts to get neonatal HSV infection onto the list of federally reportable diseases. In the meantime, Dr. Sánchez and his colleagues at Nationwide Children’s and elsewhere continue to expand their HSV research efforts.

“We plan to perform transcriptomic analysis using blood samples that were collected from these babies in order to identify markers of inflammation and immune response,” says Dr. Sánchez of his ongoing collaboration with Asunción Mejías, MD, PhD, MSCS, a coauthor of the study and physician-scientist in the Department of Infectious Diseases at St. Jude Children’s Research Hospital. “We hope this tool will help us understand if these were false positive cases or if the babies were responding immunologically to the virus. We also want to better understand the coinfections that we identified in some of these babies, and the best ways to improve early management of neonates born to mothers with active genital HSV infection.”

 

References:

  1. Fernandes ND, Arya K, Syed HA, et al. Congenital Herpes Simplex. [Updated 2024 Apr 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507897/
  2. Graf RJ, Viviana Hoyos García I, Dendi A, White NO, Pifer T, Harris R, Salamon D, Mejias A, Sánchez PJ. Mucosal Site Detection of Herpes Simplex Virus in Neonates. J Pediatr. 2024 Jul 24;275:114212. Epub ahead of print.

Image credit: Adobe Stock

 

 

 

 

About the author

Katherine (Katie) Brind’Amour is a freelance medical and health science writer based in Pennsylvania. She has written about nearly every therapeutic area for patients, doctors and the general public. Dr. Brind’Amour specializes in health literacy and patient education. She completed her BS and MS degrees in Biology at Arizona State University and her PhD in Health Services Management and Policy at The Ohio State University. She is a Certified Health Education Specialist and is interested in health promotion via health programs and the communication of medical information.

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