Cell culture and polymerase chain reaction (PCR) testing for HSV is recommended for those who present with lesions such as genital ulcers or other skin mucosa. The sensitivity of viral culture is low, especially for recurrent genital herpes lesions, and its detection sensitivity decreases rapidly when the lesions begin to heal. Nucleic acid amplification methods, including the application of PCR for HSV DNA, are more sensitive and increasingly available in healthcare settings. PCR testing can be used for the diagnosis of HSV central nervous system and systemic infections (e.g., meningitis, encephalitis, and neonatal herpes). Viral culture and PCR amplification methods have the ability to differentiate between infected HSV strains. Because viral shedding is intermittent, a negative HSV culture or PCR test (especially in patients without active lesions) does not mean that the patient is free of HSV infection. Cytologic tests that look for cellular changes associated with HSV infection (e.g., the Tzanck test) are not sufficiently sensitive or specific for the diagnosis of genital herpes and are therefore not recommended. Although direct immunofluorescence (IF) assays using fluorescein-labeled monoclonal antibodies can also detect HSV antigens from genital samples, the sensitivity of this method is similarly inadequate.