Why neonatal herpes matters
Authors: David W Kimberlin
Journal: The Lancet Global Health (2017)

Neonatal herpes is a devastating disease. A newborn baby at the start of life is ravaged by a viral infection that, in almost all cases, was acquired from his own mother. He may start with just a few tiny clusters of blisters on his skin and then progress to more severe involvement, or he may begin with uncontrollable convulsions, inability to breathe, and bleeding from any number of body sites. As the doctor rushes to understand what the cause of the baby's illness is, she or he will consider several common pathogens, including bacteria such as group B streptococcus and viruses such as enteroviruses. As the cause settles in on herpes simplex virus (HSV), however, the doctor must sit down with the parents to explain that there is a high likelihood that their baby might die, and if he survives there can be an equally high likelihood of permanent brain damage. Inevitably they will ask how this happened, and the doctor will explain that in at least 90% of cases the infection comes from the mother. Vertical transmission of a sexually transmitted disease comes with a host of documented emotional and psychosocial consequences. This is what neonatal herpes does: it ravages the lives of newborn babies and parents. In The Lancet Global Health, Katharine Looker and colleagues1Looker KJ Magaret AS May MT et al.First estimates of the global and regional incidence of neonatal herpes infection.Lancet Glob Health. 2017; (published online Jan 30.)http://dx.doi.org/10.1016/S2214-109X(16)30362-XSummary Full Text Full Text PDF PubMed Scopus (120) Google Scholar attempt what, to my knowledge, has never been done before—namely, to estimate how many times each year across the globe a doctor sits down with a mother and father to have the above conversation. They use very complex mathematical equations to reach conclusions that are simultaneously jolting and reassuring. Looking at it from one angle, 132 million women worldwide have prevalent or incident HSV-1 or HSV-2 infections during pregnancy. That means tens of millions of babies are at risk of acquiring neonatal herpes each year. Looking at it from another angle, that only 3703 and 36 415 babies actually acquire neonatal herpes each year is a good thing—except for those thousands who do become infected. These authors take on a very challenging issue. For regions of the world with higher HSV-2 seroprevalence, the risk of neonatal HSV-2 disease is high because of both increased risk of acquisition during pregnancy (when the sexual partner is HSV-2-positive), with its likelihood of transmission ranging from 25% to 60%, and increased risk of HSV-2 recurrent infection at the time of delivery, with its likelihood of transmission of about 2%. For those regions of the world with increasing HSV-1 genital disease, primarily through changing sexual practices that include the increasing practice of oral sex, the likelihood of a first-episode primary or non-primary genital HSV-1 infection increases, carrying with it the likelihood of transmission of 25–60%, although this risk might decrease since HSV-1 is less likely to reactivate in the genital tract than is HSV-2.2Kimberlin DW The Scarlet H.J Infect Dis. 2014; 209: 315-317Crossref PubMed Scopus (13) Google Scholar These complex considerations are approached in a sophisticated manner by the authors of their Article,1Looker KJ Magaret AS May MT et al.First estimates of the global and regional incidence of neonatal herpes infection.Lancet Glob Health. 2017; (published online Jan 30.)http://dx.doi.org/10.1016/S2214-109X(16)30362-XSummary Full Text Full Text PDF PubMed Scopus (120) Google Scholar and they deserve significant accolades as a consequence. However, the limitations of this work must also be emphasised. Most of the numbers presented in the study1Looker KJ Magaret AS May MT et al.First estimates of the global and regional incidence of neonatal herpes infection.Lancet Glob Health. 2017; (published online Jan 30.)http://dx.doi.org/10.1016/S2214-109X(16)30362-XSummary Full Text Full Text PDF PubMed Scopus (120) Google Scholar are estimates that are based on other estimates derived from a very small number of studies conducted in North America. What really is needed is for prospective studies to be done in countries across the world, so that actual babies with neonatal herpes are counted rather than estimated. We are starting such a study with collaborators in Peru, but much more work remains to be done on all the continents of the world. Additional global funding is required to achieve this important work, and Looker and colleagues' data illustrate why such funding would be money well spent. Several preventative opportunities are under development, including point-of-care diagnostics that could identify babies exposed to HSV at delivery and who therefore are at increased risk of neonatal herpes (NCT01878383) and vaccine development.3Stanberry LR Spruance SL Cunningham AL et al.The GlaxoSmithKline Herpes Vaccine Efficacy Study GroupGlycoprotein-D-adjuvant vaccine to prevent genital herpes.N Engl J Med. 2002; 347: 1652-1661Crossref PubMed Scopus (715) Google Scholar The prevention of genital herpes would be beneficial for several reasons, including the benefit on the psychosocial impact of genital herpes4Rosenthal SL Zimet GD Leichliter JS et al.The psychosocial impact of serological diagnosis of asymptomatic herpes simplex virus type 2 infection.Sex Transm Infect. 2006; 82: 154-157Crossref PubMed Scopus (54) Google Scholar and the prevention of HIV transmission.5Celum C Wald A Lingappa JR et al.Partners in Prevention HSV/HIV Transmission Study TeamAcyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2.N Engl J Med. 2010; 362: 427-439Crossref PubMed Scopus (420) Google Scholar I would argue, however, that the most compelling reason to prevent genital herpes is to put an end to the conversation between doctors and mothers cited above. Nothing is more important than your child. The opportunity to change this dynamic is within reach, but first efforts such as those of Looker and colleagues and the prospective studies to follow are crucial. For the sake of babies yet to be born, let's do it. I declare no competing interests. First estimates of the global and regional incidence of neonatal herpes infectionThese neonatal herpes estimates mark the first attempt to quantify the global burden of this rare but serious condition. Better collection of primary data for neonatal herpes is crucially needed to reduce uncertainty and refine future estimates. These data are particularly important in resource-poor settings where we may have underestimated cases. Nevertheless, these first estimates suggest development of new HSV prevention measures such as vaccines could have additional benefits beyond reducing genital ulcer disease and HSV-associated HIV transmission, through prevention of neonatal herpes. Full-Text PDF Open Access