Herpes Simplex

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Herpes simplex viruses are ubiquitous, host-adapted pathogens that cause a wide variety of disease states. Two types exist: herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). Both are closely related but differ in epidemiology. HSV-1 is traditionally associated with orofacial disease (see the image below), while HSV-2 is traditionally associated with genital disease. Lesion location, however, is not necessarily indicative of viral type, as HSV-1 is associated with genital infections more often than HSV-2 in some unique subpopulations.

The term herpes is derived from the Greek word “to creep or crawl” and dates back to early Greek civilization, approximately 2000 years ago, in reference to the spreading nature of herpetic skin lesions.

See Herpes Simplex Viruses: Test Your Knowledge, a Critical Images slideshow, for more information on clinical, histologic, and radiographic imaging findings in HSV-1 and HSV-2.

Also, see the 20 Signs of Sexually Transmitted Infections and Clues in the Oral Cavity: Are You Missing the Diagnosis? slideshows to help make an accurate diagnosis.

Up to 80% of herpes simplex infections are asymptomatic. Symptomatic infections can be characterized by significant morbidity and recurrence. In immunocompromised hosts, infections can cause life-threatening complications.

The prevalence of HSV infection worldwide has increased over the last several decades, making it a major public health concern. Prompt recognition of herpes simplex infection and early initiation of therapy are of utmost importance in the management of the disease.

HSV belongs to the alpha herpesvirus group. It is an enveloped virus that is approximately 160 nm in diameter with a linear, double-stranded DNA genome. The overall sequence homology between HSV-1 and HSV-2 is about 50%. HSV-1 has tropism for oral epithelium, while HSV-2 has tropism for genital epithelium. HSV infection is mediated through attachment via ubiquitous receptors to cells, including sensory neurons, leading to establishment of latency. ^[1]

HSV-1 and HSV-2 are characterized by the following unique biological properties: ^[1]

Cellular immunity is an important defense against herpes simplex. Dissemination of herpes simplex infection can occur in people with impaired T-cell immunity, such as in organ transplant recipients and in individuals with AIDS. Herpes simplex infection can also complicate burn wounds or damaged skin such as in atopic dermatitis or other allergic dermatoses.

HSV is distributed worldwide. Humans are the only natural reservoirs, and no vectors are involved in transmission. Endemicity is easily maintained in most human communities owing to latent infection, periodic reactivation, and asymptomatic virus shedding. ^[3]

HSV is transmitted by close personal contact, and infection occurs via inoculation of virus into susceptible mucosal surfaces (eg, oropharynx, cervix, conjunctiva) or through small cracks in the skin. The virus is readily inactivated at room temperature and by drying; hence, aerosol and fomitic spread are rare.

United States

HSV is the most common cause of genital ulcers in the United States. HSV-1 is usually acquired in childhood by contact with oral secretions that contain the virus. The presence of HSV-2 can be used as an indirect measure of sexual activity. Seroprevalence rates do not reflect how many of these individuals have or will have symptomatic episodes of HSV recurrence, as the presence of antibodies is poorly correlated with disease protection.

Seroprevalence: Antibodies to HSV-1 increase with age starting in childhood and correlate with socioeconomic status, race, and cultural group. By age 30 years, 50% of individuals in a high socioeconomic status and 80% in a lower socioeconomic status are seropositive. Antibodies to HSV-2 begin to emerge at puberty, correlating with the degree of sexual activity. The lifetime seroprevalence can be 20%-80%. ^[4] More than 90% of adults have antibodies to HSV-1 by the fifth decade of life. ^[1] ​A slight crossover of immunity occurs between HSV-1 and HSV-2, allowing for milder subsequent infection by the partner virus type.

International

HSV is well distributed worldwide, with over 23 million new cases per year. An increase in seroprevalence of antibodies to HSV-2 has been documented throughout the world (including the United States) over the last 20 years. ^[1]

Morbidity and mortality rates associated with HSV infections are discussed in Complications. Overall, the mortality rate associated with herpes simplex infections is related to 3 situations: perinatal infection, encephalitis, and infection in the immunocompromised host.

A national health survey conducted in the United States revealed a seroprevalence of HSV-2 antibodies in 45% of blacks, 22% of Mexican-Americans, and 17% of whites. ^[4]

Seropositivity to HSV-2 is more common in women (25%) than in men (17%). ^[4]

HSV-1 infections transmitted via saliva are common in children, although primary herpes gingivostomatitis can be observed at any age. HSV-2 infections are clustered perinatally (from a maternal episode at delivery) and primarily once sexual activity begins. HSV-2 genital infections in children can be an indication of sexual abuse. Increased age (after onset of sexual activity) and total number of sexual partners are independent factors associated with increased seroprevalence of HSV-2 antibodies. ^[4]

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Folusakin O Ayoade, MD Clinical Fellow, Division of Infectious Diseases, LSU Health Science Center

Folusakin O Ayoade, MD is a member of the following medical societies: American College of Physicians, American Medical Association, Infectious Diseases Society of America, Society of Hospital Medicine

Disclosure: Nothing to disclose.

John R Todd, IV, MD Professor of Clinical Medicine, Department of Medicine, Section of Infectious Diseases, Louisiana State University School of Medicine in Shreveport

John R Todd, IV, MD is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Charles V Sanders, MD Edgar Hull Professor and Chairman, Department of Internal Medicine, Professor of Microbiology, Immunology and Parasitology, Louisiana State University School of Medicine at New Orleans; Medical Director, Medicine Hospital Center, Charity Hospital and Medical Center of Louisiana at New Orleans; Consulting Staff, Ochsner Medical Center

Charles V Sanders, MD is a member of the following medical societies: American College of Physicians, Alliance for the Prudent Use of Antibiotics, The Foundation for AIDS Research, Southern Society for Clinical Investigation, Southwestern Association of Clinical Microbiology, Association of Professors of Medicine, Association for Professionals in Infection Control and Epidemiology, American Clinical and Climatological Association, Infectious Disease Society for Obstetrics and Gynecology, Orleans Parish Medical Society, Southeastern Clinical Club, American Association for the Advancement of Science, Alpha Omega Alpha, American Association of University Professors, American Association for Physician Leadership, American Federation for Medical Research, American Geriatrics Society, American Lung Association, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Association of American Medical Colleges, Association of American Physicians, Infectious Diseases Society of America, Louisiana State Medical Society, Royal Society of Medicine, Sigma Xi, Society of General Internal Medicine, Southern Medical Association

Disclosure: Received royalty from Baxter International for other.

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Larry I Lutwick, MD, FACP Editor-in-Chief, ID Cases; Moderator, Program for Monitoring Emerging Diseases; Adjunct Professor of Medicine, State University of New York Downstate College of Medicine

Larry I Lutwick, MD, FACP is a member of the following medical societies: American Association for the Advancement of Science, American Association for the Study of Liver Diseases, American College of Physicians, American Federation for Clinical Research, American Society for Microbiology, Infectious Diseases Society of America, Infectious Diseases Society of New York, International Society for Infectious Diseases, New York Academy of Sciences, Veterans Affairs Society of Practitioners in Infectious Diseases

Disclosure: Nothing to disclose.

Meena Seenivasan, MD Fellow, Department of Infectious Disease, State University of New York Health Science Center at Brooklyn

Disclosure: Nothing to disclose.

Thomas J Marrie, MD Dean of Faculty of Medicine, Dalhousie University Faculty of Medicine, Canada

Thomas J Marrie, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society for Microbiology, Association of Medical Microbiology and Infectious Disease Canada, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Swati Kumar, MD Assistant Professor of Pediatrics, Division of Infectious Diseases, Medical College of Wisconsin, Consulting Staff, Children’s Specialty Group, Children’s Hospital of Wisconsin

Swati Kumar, MD is a member of the following medical societies: American Academy of Pediatrics, Infectious Diseases Society of America, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Michelle R Salvaggio, MD, FACP Assistant Professor, Department of Internal Medicine, Section of Infectious Diseases, University of Oklahoma College of Medicine; Medical Director of Infectious Diseases Institute, Director, Clinical Trials Unit, Director, Ryan White Programs, Department of Medicine, University of Oklahoma Health Sciences Center; Attending Physician, Infectious Diseases Consultation Service, Infectious Diseases Institute, OU Medical Center

Michelle R Salvaggio, MD, FACP is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America

Disclosure: Received honoraria from Merck for speaking and teaching.

Herpes Simplex

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