NEONATAL HERPES IS A SERIOUS consequence of herpes simplex virus (HSV) infection. Transmission of HSV from mother to infant occurs in utero or intrapartum. Rarely, infants are infected postpartum by direct contact with infected mothers, caregivers, or other contacts.1 Up to 80% of neonates with herpes are born to mothers without any clinical symptoms or known history of genital herpes.2 Clinical findings of neonatal herpes vary, but may be classified into 3 main clinical syndromes with considerable overlap: infection limited to the skin, eyes, and mouth (SEM disease); central nervous system disease (CNS); or disseminated infection.1 Laboratory confirmation of HSV infection includes isolation by culture and identification of HSV infection by antigen detection, nucleic acid amplification, or immunofluorescence assay from a clinical or an autopsy specimen.
Without treatment, case fatality for neonatal herpes is 85%.3 Even with treatment, the case fatality rate can be over 50% among infants with disseminated infection, though lower among those treated for CNS (13%) or SEM (0%) disease.4 Although cesarean delivery is recommended for women noted to have active herpes lesions at the onset of labor, the efficacy of this and other prevention approaches, such as serologic screening during pregnancy, is not well documented.5 Moreover, the interval between onset of symptoms in the infant and institution of treatment had not changed in a decade.4 Early diagnosis of neonatal herpes may be facilitated by greater communication with physicians about occurrence of neonatal herpes cases in their locales, which could be assisted by local case reporting.
Although neonatal herpes is not nationally reportable, some states include this disease as a reportable condition. A previous assessment of neonatal herpes reporting documented programmatic constraints to neonatal herpes reporting.6 We conducted an updated national assessment of neonatal herpes reporting practices to describe surveillance systems in those states in which neonatal herpes was reportable during 2000–2005.
Materials and Methods
From September to December 2005, an e-mail query was sent to directors and managers of Sexually Transmitted Disease (STD) programs in the United States to identify states in which neonatal herpes was reportable. Programs in all 50 states responded to the query. To assess reporting practices, we used a standardized evaluation instrument to collect data from programs with neonatal herpes reporting with regards to (a) process and management of neonatal herpes reporting and (b) number of reported cases.
The rate of neonatal herpes was calculated using the reported cases divided by the number of live births (obtained from census information) that occurred while the surveillance was in place. Because the number of reported cases in 2005 was not available in all 9 states when this assessment was conducted, we present the rate from 2000 to 2004.
We identified 2 states, Hawaii and Indiana, in which neonatal herpes was reportable in the past but not since the late 1990s. Indiana discontinued neonatal herpes reporting because the data were not being utilized; however, the state will reinstitute neonatal herpes reporting as of January, 2008. Hawaii discontinued neonatal herpes reporting after a systematic review of reportable conditions; few cases were reported and neonatal herpes reporting did not meet their minimal criteria for reportable conditions. Nine states (18%) had reporting systems for neonatal herpes at some point from 2000 to 2005: Connecticut, Delaware, Florida, Louisiana, Nebraska, Massachusetts, Ohio, South Dakota, and Washington. STD programs were responsible for the reporting activity in all the 9 states.
Only 1 state had a surveillance case definition for reporting, which was as follows: “A case presenting with any symptoms of SEM, and/or CNS and/or disseminated infection in an infant ≤60 days of life.” A confirmed case was, “a case that is laboratory confirmed determined by isolation of HSV in specimens from infection sites, or by detection of HSV in cerebrospinal fluid”. In the other 8 states, health care provider diagnosis of cases was the basis for reporting. The age range required for case reporting varied across states: infants ≤60 days old were reported in 3 states, infants ≤1 year of age in 4 states, and children ≤4 years of age in 1 state. In 1 state, there was no age specification for a case.
All reporting systems were mandated by state law and were passive. There were specific requirements for the time frame of reporting, which ranged from 24 hours to 5 days from the date of diagnosis and varied by state. All reporting systems involved clinicians, hospitals, and local health departments; all collected limited demographic information such as name, age, dates of hospitalization, and discharge date. Only 1 state required laboratory confirmation of a case. One state obtained information on treatment, and 1 state on outcome. Two states routinely validated data by comparing case reports from clinicians with those from laboratories to ensure that there was no duplication.
Annual state rates of reported cases ranged from 0 to 54.4 cases per 100,000 live births. Few cases were reported in any state (range, 0–13 per year) (Table 1). Overall, the rate was 4 cases per 100,000 live births over 5 years, from 2000 to 2004.
We determined that neonatal herpes was reportable in 9 states (18%) during 2000–2005. This is somewhat different from a previous assessment that identified 3 states with neonatal herpes reporting;6 the previous assessment was not able to survey all program areas and had different methods of assessment. We identified significant programmatic barriers to successful identification of neonatal herpes cases, similar to the previous evaluation.
Neonatal herpes is a serious disease resulting in significant sequelae and high case fatality. The estimated incidence of neonatal herpes varies widely based upon methods utilized. However, neonatal herpes reporting as currently practiced does not appear to be a reliable indicator of neonatal herpes morbidity. Using the international classification of diseases, 9th revision (ICD-9), 3 population-based assessments in CA and WA using state birth certificate data and state hospital discharge data have found incidence rates for neonatal herpes of 8.4, 11.7, and 12.1 cases per 100,000 live births annually, respectively.7–9 A prospective study of women seen in a variety of clinical settings in Washington State found that the neonatal herpes rate was 54 cases per 100,000 live births among HSV seronegative pregnant women, 22 cases per 100,000 live births among HSV-2 seropositive women, and 26 cases per 100,000 live births among HSV-1 seropositive women.10 Of note, a national surveillance evaluation in Canada found an incidence of 5.9 cases in 100,000 births.11 The reasons for differences in neonatal herpes incidence rates are unclear.
In the present evaluation, we found the rate of neonatal herpes through the existing reporting systems was 4 cases per 100,000 live births, with a wide range in rates, and with some states having no cases reported over the entire 6 years, suggesting an underreporting of neonatal herpes cases. Of note, 1 state conducted 2 evaluations comparing reported cases with statewide hospital discharge data and found that the reporting system identified 17% (11/65) of infants who had been diagnosed with neonatal herpes from 1992 to 1996, and 13% (9/67) from 2002 to 2004 (personal communications, Mark Stenger and Mark Aubin).
The reporting systems for neonatal herpes could be enhanced by use of a standard case definition, active review of available data, and dissemination of information about reported cases. A standard case definition would enhance surveillance for neonatal herpes by allowing states to compare reported cases and trends. Periodic assessments of reported neonatal herpes cases, either by comparing hospital discharge data with medical records or with laboratory data, could significantly improve data quality and completeness of reporting. Timely dissemination of findings from data analyses and feedback concerning reported cases could refine measurements of the burden of disease and enhance overall quality of the reporting system. This feedback could also increase awareness of the reporting requirement and enhance completeness of the reporting.
This evaluation of neonatal herpes reporting is subject to limitations. The assessment was based on interviews conducted with persons responsible for the reporting systems at the state health departments and did not include interviews with laboratories or clinicians. In addition, this report does not include information on the reporting systems in New York State and New York City, where neonatal herpes became reportable in early 2006 after our assessment. Finally, our assessment did not include measures of quality or completeness of the data collected, nor did we review surveillance reports from the states.
Neonatal herpes is not currently a nationally reportable disease, although recent editorials and experts have advocated for this.12–13 This report suggests that neonatal herpes reporting, as currently implemented, has not been an adequate means by which to assess burden of disease. CDC is collaborating with the Council of State and Territorial Epidemiologists (CSTE) to improve surveillance for neonatal herpes through development of a standard case definition for those locales where the disease is reportable14; if such a case definition is adopted, the impact on reporting will need to be evaluated. However, there are other approaches by which burden of disease may also be assessed. As discussed above, population-based hospital discharge data are useful7,8; similarly administrative databases have also been used to assess burden, although research is needed to help clarify which diagnostic codes should be utilized.15 A different approach was employed in a 3-year period in Canada; neonatal herpes cases were reported by the nation’s pediatricians, monthly.11 This data provided extensive demographic and clinical information on neonatal herpes cases.
No one approach appears to be completely satisfactory. Although hospital discharge and administrative data can help track overall disease occurrence, they provide less clinical or laboratory information, such as the severity of disease or the virus type responsible (i.e., HSV-1 or HSV-2); such information will be important to track if impact of a future herpes simplex vaccine is to be monitored. The Canadian approach provided such information, but the one-time evaluation did not allow assessment of trends. A combination of data sources may be optimal to provide reliable estimates of neonatal herpes, including demographic and clinical information, and neonatal herpes incidence trends in the United States. Further discussion with experts in public health, academics and laboratory medicine will be necessary to achieve the appropriate platform for neonatal herpes surveillance.
1. Stagno S, Whitley RJ. Herpesvirus infections in neonates and children: Cytomegalovirus and herpes simplex virus. In Holmes KK, Sparling PF, Mardh P-A, et al., eds. Sexually Transmitted Diseases, 3rd ed. New York: Mc-Graw Hill, 1999:1191–1212.
2. Whitley RJ. Herpes simplex infection. In: Remington JS, Klein JO, eds. Infectious Diseases of the Fetus and Newborn Infant, 3rd ed. Philadelphia: WB Saunders, 1990:282–305.
3. Whitley RJ, Nahmias AJ, Soong SJ, et al. Vidarabine therapy of neonatal herpes simplex virus infection. Pediatrics 1980; 66:495–501.
4. Kimberlin DW, Lin CY, Jacobs RF, et al. Natural history of neonatal herpes simplex virus infections in the acyclovir era. Pediatrics 2001; 108:223–229.
7. Gutierrez KM, Falkovitz Halpern MS, Maldonado Y, et al. The epidemiology of neonatal herpes simplex virus infection in California from 1985 to 1995. J Infect Dis 1999; 180:199–202.
8. Mark KE, Kim NH, Wald A, et al. Targeted prenatal herpes simplex virus testing: Can we identify women at risk of transmission to the neonate? Am J Obstet Gynecol 2006; 194:408–414.
9. Morris SR, Bauer HM, Samuel MC, et al. Neonatal herpes morbidity and mortality in California, 1995–2003. Sex Transm Dis. In press.
10. Brown ZA, Wald A, Morrow RA, et al. Effect of serologic status and cesarean delivery on transmission rates of herpes. Simplex virus from mother to infant. JAMA 2003; 289:203–209.
11. Kropp RY, Wong T, Cormier L, et al. Neonatal herpes simplex virus infections in Canada: Results of a 3-year national prospective study. Pediatr 2006; 117:1955–1962.
12. Handsfield H, Waldo AB, Brown ZA, et al. National herpes should be a reportable disease. Sex Transm Dis 2005; 32:521–525.
13. Donoval BA, Passaro DJ, Klausner JD. The public health imperative for a neonatal herpes simplex virus infection surveillance system. Sex Transm Dis 2006; 33:170–174.
15. Whitley R, Davis EA, Suppapanya N. Incidence of neonatal herpes simplex virus infections in a managed-care population. Sex Transm Dis 2007;34:704–708.