is a relatively infrequent infection, occurring in between 1 in 1,700 and 1 in 12,500 births. However, it is estimated that 25 to 50% of women who have acquired HSV during pregnancy and have vaginal deliveries will transmit the disease to their child, whereas ≤1% with recurrent infection will do so. Notably, most cases of genital HSV in women are asymptomatic, though cervical viral shedding still occurs. Other factors that increase the likelihood of infection are prolonged rupture of membranes, a mother who is seronegative for HSV-2 (suggesting acute infection), and the use of fetal scalp monitors. Of neonates with herpes infections, ~80% are infected during passage through an infected birth canal, while ~6 to 14% are infected in utero and the remaining are infected postpartum.
Most neonatal HSV infections occur in the second to third week of life. There are three forms of neonatal HSV infection: (i) skin, eyes, and mouth disease; (ii) central nervous system (CNS) disease; and (iii) disseminated disease. The most benign form, which is seen in 45% of cases, causes infection localized to the skin, eyes, and mouth. If recognized, it can be effectively treated with antiviral agents such as acyclovir. CNS-associated infections account for 30% of cases. These children have nonspecific CNS symptoms not unlike those of neonatal bacterial meningitis, including seizures, lethargy, high fevers, poor feeding, and irritation. Lesions may or may not be present. Mortality approaches 50% in untreated children, and long-term neurologic sequelae such as developmental delay, epilepsy, blindness, and cognitive disabilities are seen in half of the survivors. The most severe manifestation of disease is disseminated infection, which occurs in ~25% of cases. In this infection, multiple organs, including the brain, may be infected. These individuals typically have a viral exanthem in the setting of CNS infection and/or multiorgan failure. Up to 50% of cases do not have a rash. If the infection is untreated, mortality is very high, reaching 80%. Even with appropriate therapy, mortality for disseminated disease is 30%, and those who survive often have profound neurologic sequelae as mentioned above.
4. HSV, like all herpesviruses, causes a lifelong, latent infection. In genital tract infections, the virus enters a latent state in the sacral nerve ganglia. Recurrences occur when the virus replicates in the neuron and is carried along the peripheral nerves to the epithelium. Of adults with HSV-2, only 10 to 25% have a clinical history of genital herpes lesions. HSV-infected individuals can intermittently shed HSV in the absence of symptoms and therefore contribute to the transmission of HSV. Both condom use and antiviral suppression decrease transmission. Symptomatic recurrences may occur as frequently as 8 to 10 times per year, although the majority of individuals have significantly fewer episodes. Recurrences are generally milder than the primary episode of disease.
5. HSV-2 infects ~16% of individuals in the United States. Infections are more common in females (21%) than in males (12%) and are more common in black individuals (39%, versus 12% for whites). Other risk factors for HSV-2 infection include early age of first sexual encounter, a high number of sexual partners, history of other sexually transmitted infections, and lower socioeconomic status. Infection rates among commercial sex workers may approach 100%. Although HSV-2 infection rates increased significantly from 1976 to 1994, with the highest rate of increase in individuals <30 years old, this trend has reversed in recent years.
6. There are two distinct serotypes of HSV—HSV-1 and HSV-2. HSV-1 is an infection primarily of the oropharyngeal mucosa, with latent infection occurring in the trigeminal ganglion, while HSV-2 primarily infects the genital mucosa, though either serotype can be seen in these anatomic sites. HSV-1 infections are typically acquired in early childhood, while HSV-2 infections occur after the individual becomes sexually active. There has been a noticeable increase in HSV-1 genital infections over the last 2 decades, with some studies quoting an incidence of up to 50%. Possible explanations for this increase include increased oral-genital contact; increased HSV-1 acquisition in childhood, providing more viral exposure in adolescence; and/or a decrease in HSV-1 infection in childhood, making children more susceptible when they become sexually active. Although both serotypes are neurotropic, HSV-1 appears to cause more severe CNS infection affecting the temporal and frontal lobes. In contrast to aseptic meningitis associated with primary genital HSV-2 infection and neonatal CNS infection, herpes encephalitis in adults and older children is most often due to HSV-1 infection. Herpes encephalitis is a rare, sporadic CNS viral infection and is the most common cause of nonepidemic viral encephalitis in adults in the United States. Patients present with fever, headache, and encephalopathic findings such as altered consciousness, behavioral and speech disturbances, and focal or diffuse neurologic signs. The diagnosis can be confirmed by detecting HSV directly using fluorescent antibody staining of tissue obtained by brain biopsy. Because brain biopsy is dangerous, alternative means of making this diagnosis have been sought. Two studies have carefully evaluated the sensitivity of HSV PCR compared with histopathologic evaluation of brain tissue, reporting sensitivities of 97 to 98% for PCR. Therefore, HSV PCR of CSF has become the standard method for diagnosing HSV CNS infection. It is not clear why certain patterns of CNS infection with either HSV-1 or HSV-2 result in different CNS manifestations. The age of the patient, the route of viral dissemination (e.g., neural versus hematogenous), preexisting immunity, and/or specific viral properties may be factors.
REFERENCES
1. Centers for Disease Control and Prevention (CDC). 2010. Seroprevalence of herpes simplex virus type 2 among persons ages 14-49 years—United States, 2005–2008. MMWR Morb Mortal Wkly Rep 59:456–459.
2. Corey L, Wald A. 2009. Maternal and neonatal herpes simplex virus infections. N Engl J Med 361:1376–1385.
3. Lakeman FD, Whitley RJ, National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. 1995. Diagnosis of herpes simplex encephalitis: application of polymerase chain reaction to cerebrospinal fluid from brain-biopsied patients and correlation with disease. J Infect Dis 171:857–863.
4. Tang YW, Mitchell PS, Espy MJ, Smith TF, Persing DH. 1999. Molecular diagnosis of herpes simplex virus infections in the central nervous system. J Clin Microbiol 37:2127–2136.
5. Whitley RJ, Roizman B. 2001. Herpes simplex virus infections. Lancet 357:1513–1518.
CASE 5
This 26-year-old woman was referred to a public health clinic as a result of contact tracing in a case of gonorrhea. The woman, who had recently had unprotected sexual intercourse, had no symptoms. Physical examination was normal. Pelvic examination demonstrated a white vaginal discharge but was otherwise unremarkable. A cervical swab was obtained and submitted for Chlamydia trachomatis and Neisseria gonorrhoeae testing by a nucleic acid amplification test (NAAT). Examination of a wet mount of the vaginal discharge revealed the presence of a protozoan with a characteristic jerky motility. Figure 5.1 shows a Giemsa stain of the organism.
1 1. What organism did the wet preparation demonstrate? What other organism can cause vaginitis and can be detected by wet mount?
2 2. What other methodologies are available for detection of this organism?
3 3. How is infection with this organism most commonly acquired? What clinical presentations occur in women infected with this organism? In men infected with this organism?
4 4. This patient was asymptomatic when examined. She had had sexual contact with a partner who had a positive culture for N. gonorrhoeae. What would be appropriate antimicrobial therapy for this patient?
5 5. Why is infection with this organism of special concern in pregnant women? Would therapy be any different if
