eMedicine Specialties > Infectious Diseases > Viral Infections

Enteroviruses

Author: Alexander Velazquez, MD, Fellow, Department of Infectious Diseases, Orlando Regional Medical Center
Coauthor(s): Mark R Wallace, MD, FACP, FIDSA, Clinical Professor of Medicine, Florida State University College of Medicine; Infectious Disease Fellowship Director, Orlando Regional Medical Center; Smeeta Sinha, MD, Staff Physician, Department of Dermatology, UMDNJ-New Jersey Medical School; Rajendra Kapila, MD, MBBS, Professor of Medicine, Department of Medicine, UMDNJ, New Jersey Medical School; Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School; Pratibha Dua, MD, MBBS, Staff Physician, Department of Internal Medicine, The Brooklyn Hospital Center
Contributor Information and Disclosures

Updated: Nov 10, 2009

Introduction

Background

The human enteroviruses are ubiquitous viruses that are transmitted from person to person via direct contact with virus shed from the gastrointestinal or upper respiratory tract. The enteroviruses belong to the Picornaviridae family of viruses and are traditionally divided into 5 subgenera based on differences in host range and pathogenic potential.1 Each subgenus contains a number of unique serotypes, which are distinguished based on neutralization by specific antisera. The subgenera include polioviruses, coxsackievirus (groups A and B), and echoviruses.

A total of 72 serotypes were originally identified by conventional methods; 64 serotypes remain after recognition of redundant serotypes. Three serotypes comprise the polioviruses, 23 serotypes comprise coxsackievirus group A, 6 serotypes comprise coxsackievirus group B, and 29 serotypes comprise the echoviruses. A new classification scheme has been adopted that divides all nonpolio enterovirus into 4 groups designated A through D based on the homology within RNA region coding for the VP1 capsid protein.2 More recently, many new serotypes that are not included in the original classification have been characterized by molecular methods, bringing the number of known serotypes to more than 90.3,4

Virology

  • The enteroviruses are icosahedral nonenveloped viruses that are approximately 30 nm in diameter.
  • They have a capsid composed of 60 subunits each formed from 4 proteins (VP1 to VP4).
  • They are stable at a pH from 3-10, distinguishing them from other picornaviruses (including rhinoviruses), which are unstable below pH 6.
  • A linear, single-strand RNA genome of about 7.5 kb is enclosed by the capsid; the translation product is a single polyprotein that is cleaved after translation by viral-coded proteases into the structural proteins (VP1 to VP4), RNA polymerase, proteases, and other nonstructural proteins.5
  • Enteroviruses resist lipid solvents, ether, chloroform, and alcohol. They are inactivated at temperatures above 50°C but remain infectious at refrigerator temperature.
  • Molar MgCl2 reduces thermolability at higher temperatures.
  • The viruses are inactivated by ionizing radiation, formaldehyde, and phenol.

Enteroviruses cause a wide range of infections. Poliovirus, the prototypical enterovirus, can cause a subclinical or mild illness, aseptic meningitis, or paralytic poliomyelitis, a disease that has been eradicated in the United States and other developed countries. The nonpolio viruses (group A and B coxsackieviruses, echoviruses, enteroviruses) continue to be responsible for a wide spectrum of diseases in persons of all ages, although infection and illness occur most commonly in infants.

Coxsackievirus infection is the most common cause of viral heart disease. Group A coxsackieviruses may cause flaccid paralysis, while group B coxsackieviruses cause spastic paralysis. Other diseases associated with group A coxsackievirus infections include hand-foot-and-mouth disease (HFMD) and hemorrhagic conjunctivitis, while group B coxsackievirus is associated with herpangina, pleurodynia, myocarditis, pericarditis, and meningoencephalitis. Aseptic meningitis and the common cold are associated with both groups.

Diseases caused by echoviral infections range from the common cold and fever to aseptic meningitis and acute hemorrhagic conjunctivitis (AHC).

Pathophysiology

Enteroviruses are transmitted predominantly via the fecal-oral route. However, there are some exceptions, including coxsackievirus A21, which is spread mainly by respiratory secretions,6 and enterovirus 70, which is shed in tears and spread via fingers and fomites.7

Upon entry into the oropharynx, the virus replicates in submucosal tissues of the distal pharynx and alimentary tract.8 Viral particles are shed in the feces and in upper respiratory tract secretions for days prior to symptom onset. The average incubation period is 3-10 days, during which the virus migrates to regional lymphoid tissue and replicates. Minor viremia results, which is associated with the onset of symptoms and viral spread to the reticuloendothelial system (spleen, liver, bone marrow).9

Dissemination to target organs follows, and viral replication in target organs produces the major viremia with possible secondary seeding of the CNS. Potential target organs include the skin and CNS. Infectious virus is shed from the upper respiratory tract for 1-3 weeks and from the feces for 3-8 weeks. Enteroviruses undergoes a high rate of mutation during replication in the gastrointestinal tract, where single-site mutations can occur in the 5' noncoding region of the attenuated polioviruses; this can lead to prolonged excretion and neurovirulence.10

The neuropathy of paralytic diseases caused by enteroviruses is due to direct cellular destruction. Neuronal lesions occur mainly in anterior horn cells of the spinal cord. The 3 serotypes of poliovirus all bind to the cell surface receptor CD155.

Immunity and immune response

  • Immunity to enterovirus is serotype-specific. Intact humoral immunity is required for the control and eradication of enteroviral disease.
  • T lymphocytes do not contribute to viral clearance and, in coxsackievirus B3 myocarditis, may contribute to myocardial inflammation.11
  • Humoral immunity (antibody-mediated) mechanisms operate both in the alimentary tract (to prevent mucosal infection) and in the blood (to prevent dissemination to target organs).
  • Secretory immunoglobulin A (IgA) appears in nasal and alimentary secretions 2-4 weeks after the administration of live-attenuated oral poliovirus vaccine (OPV) and persists for at least 15 years.12 Upon re-exposure to infectious virus, high titers of secretory IgA antibodies prevent or substantially reduce poliovirus shedding; higher secretory IgA titers lead to better immunity.12
  • Immunoglobulin M (IgM) antibodies appear as early as 1-3 days after enteroviral challenge and disappear after 2-3 months.12
  • Immunoglobulin G (IgG) antibody, which is generally detected 7-10 days after infection, is mostly of the IgG1 and IgG3 subtypes. Serum neutralizing IgG antibodies persist for life after natural enteroviral infections.13
  • Macrophage function is also a critical component of the immune response in enteroviral infections; ablation of macrophage function in experimental animals markedly enhances the severity of coxsackievirus B infections.14

Frequency

United States

  • Nonpolio enteroviruses are responsible for 10-20 million symptomatic infections per year and are more prevalent among children of lower socioeconomic class, probably because of crowding, poor hygiene, and opportunities for fecal contamination.
  • AHC was first recognized in the United States in 1981 during an epidemic in Florida; few cases have been reported since. The prevalence is higher in southern areas than in northern areas.
  • Between 2002 and 2004, echoviruses 9 and 30 were the most commonly reported enterovirus serotypes in the United States.15 In contrast, other enterovirus serotypes (eg, echovirus 1, coxsackievirus B6, and enteroviruses 68 and 69) are rarely reported and appear to have little epidemic potential.16
  • Coxsackievirus A is likely underrepresented because only some serotypes are readily isolated in cell culture.17
  • National or regional outbreaks of aseptic meningitis are occasionally reported, such as the echovirus 30 outbreaks in the United States between 1989 and 1992 and in 2003 and echovirus 13 and echovirus 18 outbreaks in 2001. Aseptic meningitis is no longer a nationally notifiable disease in the United States.

International

  • Enteroviruses are distributed worldwide and are influenced by season and climate. Infections occur in summer and early fall in temperate areas, while tropical and semitropical areas bear the brunt all year.
  • AHC occurs as epidemics in tropical countries during the hot and rainy season. It was first recognized in 1969 in Ghana (Apollo disease) and Indonesia. AHC is also epidemic in India and the Far East.
  • The worldwide prevalence of poliomyelitis has decreased significantly because of improved economic conditions and availability of vaccines. The last case of wild polio in the Americas occurred in Peru in 1991. In 1994, the World Health Organization declared polio eradicated from the Western Hemisphere. In 2000, 7 cases of poliomyelitis due to a mutated polio strain related to oral polio vaccine were reported from Haiti and the Dominican Republic. Polio remains a significant disease in the developing world, and, in 2003, 6 endemic countries were identified: Afghanistan, Egypt, India, Niger, Nigeria, and Pakistan.
  • In 2008, 1,652 confirmed cases of paralytic polio were reported worldwide. Polio is endemic in 4 countries: Afghanistan, India, Nigeria, and Pakistan. In addition, 14 other previously polio-free countries (Angola, Burkina Faso, Benin, Central Africa Republic, Chad, Côte d'Ivoire, The Democratic Republic of Congo, Ghana, Ethiopia, Nepal, Niger, Sudan, Tango) have reported cases in 2008-2009 (114 cases through August 2009) as a result of importations.18,19 As of September 2009, 969 cases of polio (including wild polio strains and oral vaccine–derived) had been reported in endemic and nonendemic countries.20

Mortality/Morbidity

  • More than 90% of infections caused by the nonpolio enteroviruses are asymptomatic or result in only an undifferentiated febrile illness.21
  • Myopericarditis carries a mortality rate of 0%-4%. Myocarditis carries a higher mortality rate than pericarditis. Additionally, murine model studies have suggested that a deficiency of complement receptors 1 and 2 leads to increased morbidity in coxsackie B3 infections, including myocarditis, dilated cardiomyopathy, and fibrosis.22
  • Prior to the vaccine era, the mortality rate in polio epidemics was 5%-7%.
  • The overall risk of OPV-related disease is estimated to be 1 case per 2.6 million doses of OPV. The inactivated poliovirus vaccine (IPV) was incorporated into the routine polio vaccination in Europe and Canada in the 1980s. IPV has been used in the United States since 2000; OPV is no longer used in the United States.
  • Despite the risk of OPV-related paralysis, it is still the preferred vaccine for global polio eradication in developing nations (see Deterrence/Prevention).

Sex

  • The male-to-female ratio of myopericarditis is 2:1. The risk of cardiac involvement is higher during pregnancy and immediately postpartum.
  • The prevalence of polio infection is equal in boys and girls, although paralysis is more common in boys. Among adults, women are at increased risk of infection and the postpolio syndrome.
  • Aseptic meningitis is approximately twice as common in males as in females.

Age

  • Enteroviral infections are most common in young children. Herpangina primarily affects children aged 3 months to 16 years. Poliomyelitis is observed in children younger than 15 years. Aseptic meningitis due to enteroviral infection is more common in infants than in adults. Most cases of pleurodynia occur in children and adults younger than 30 years.
  • Myopericarditis is most prevalent in young adults, especially those who are physically active. AHC is most prevalent in adults aged 20-50 years.
  • Neonates are at high risk for severe sepsis due to enterovirus infections.

Clinical

History

Polio

  • Disease due to wild-type poliovirus infection no longer occurs in the Western Hemisphere, and a World Health Organization (WHO) international eradication program is making significant progress in the rest of the world.20
  • Patients with abortive polio present with symptoms similar to those of other viral infections, including fever, headache, sore throat, loss of appetite, vomiting, and abdominal pain. Neurologic symptoms are typically not reported.
  • The symptoms of nonparalytic polio are similar to those of abortive polio but are more intense. Patients report stiffness of the posterior muscles of the neck, trunk, and limbs.
  • Paralytic polio presents similarly to nonparalytic polio. It is an acute febrile illness characterized by aseptic meningitis and weakness or paralysis of one or more extremities, along with weakness of one or more muscle groups. Exercise increases the severity of paralytic polio, especially during the first 3 days of the major illness. Intramuscular injections or skeletal muscle injury predisposes to localization of polio to that extremity (termed provocation poliomyelitis).
    • Spinal: Patients have a prolonged prodrome, with features of aseptic meningitis followed in 1-2 days by weakness and, eventually, paralysis.
    • Bulbar: Cranial nerves are involved, most commonly IX, X, and XII. Tonsillectomy increases the risk of bulbar polio. Patients are unable to swallow smoothly. They accumulate pharyngeal secretions, have a nasal twang to the voice, and develop paralysis of vocal cords, causing hoarseness, aphonia, and, eventually, asphyxia.
    • Polioencephalitis: This form is principally reported in children. Unlike in other forms of polio, seizures are common and paralysis may be spastic.

Nonpolio viruses

More than 90% of infections caused by the nonpolio enterovirus are asymptomatic or result only in an undifferentiated febrile illness.21

  • Pleurodynia
    • Group B coxsackieviruses, particularly B3 and B5, are the most important causes of epidemic pleurodynia. Multiple family members may be affected.23,24
    • Pleurodynia manifestations include a sudden onset of fever accompanied by muscular pain in the chest and abdomen.25 The pain is spasmodic in nature, with spasms lasting 15-30 minutes and worsening during inspiration or coughing. This paroxysmal pain is characteristically associated with fever, peaking within 1 hour after onset of each paroxysm and subsiding with the subsequent paroxysm. Headache, nausea, and vomiting are also frequently reported.
  • Myopericarditis
    • Enteroviruses appear to be the most common viral cause of myopericarditis and account for at least half of all cases of acute myopericarditis.
    • Neonatal infections typically develop within the first week of life, and involvement is predominantly myocardial. In contrast, older children and adults usually present with symptoms of pericarditis.
    • The typical presentation in adolescents and adults is shortness of breath, chest pain, and fever 1-2 weeks following an upper respiratory tract infection. Chest pain may be dull or sharp; it is worsened by inspiration and may improve with sitting and leaning forward. It can be differentiated from angina by lack of response to nitroglycerin.
    • Enteroviral myocarditis can present as acute myocardial infarction associated with arrhythmias and heart failure. Some patients with myocardial infarction who have normal findings on coronary angiographic studies have been shown to have myocarditis by radiolabeled antimyosin antibody cardiac scanning.26
  • Acute hemorrhagic conjunctivitis
    • This highly contagious ocular infection can cause large-scale epidemics. AHC was first described in 1969. Enterovirus 70 is the most common etiology in epidemics. Coxsackievirus A24 causes a similar disease. AHC was initially recognized in Ghana and Indonesia and is now epidemic in India and the Far East.27
    • The first reported outbreak of AHC in United States was Key West, Florida, in 1981; subsequently, 2,500 cases were reported in Miami. Since then, with the exception of few imported cases, AHC activity has not been reported in the United States.28
    • The mode of transmission is from finger or fomite to eye. AHC is highly contagious, and crowding and unsanitary conditions favor spread. Reuse of water for bathing and sharing of towels have been implicated as factors contributing to the spread of infection.29,7
    • Onset is abrupt, and the most common symptoms include ocular pain and burning, swelling of the eyelids, and the sensation of a foreign body in the eye. Patients may also experience photophobia and watery discharge. The other eye becomes involved within hours of the first eye.
    • Nonspecific symptoms such as fever, malaise, and headache may be present. The symptoms typically improve by the second or third day of infection, and recovery is complete within 7-10 days.
  • Nonspecific febrile illness
    • This is the most common presentation of enterovirus infection.
    • More than 90% present with a nonspecific febrile illness that manifests as sudden fever (temperature, 101-104°F). The fever may last for as long as a week and may show a biphasic pattern.21
    • Patients may also report myalgia, headache, sore throat, nausea, vomiting, mild abdominal discomfort, and diarrhea.
  • Aseptic meningitis
    • Enteroviral infections (group B coxsackievirus and echovirus) account for 90% of cases of aseptic meningitis in patients younger than one year and 50% of cases in older children and adults.30,31
    • The clinical presentations of aseptic meningitis vary greatly. Prodromal symptoms include fever, chills, headache, photophobia, and nuchal rigidity. Rash and upper respiratory tract symptoms may also occur. In infants, fever and irritability are the most common symptoms.32
    • Fever and meningeal signs subside within 2-7 days.
    • Enterovirus 71, which causes HFMD, has also been associated with a particularly more aggressive and, in some instances, fatal CNS infection in children. It manifests as flaccid motor paralysis and brain stem encephalitis. Large outbreaks were reported in the late 1990s in Eastern Europe, Russia, Thailand, and Taiwan.33
  • Herpangina
    • Coxsackie A virus is the main etiologic agent of herpangina, described as a vesicular enanthem of the tonsillar fauces and soft palate that principally affects children aged 3-10 years.34 Other serotypes have been isolated including enterovirus 71 (EV71), which has cause recent outbreaks and epidemics in South-East Asia35
    • Symptoms include sudden onset of fever, sore throat, and difficulty swallowing, followed a day later by a painful vesicular eruption of the oral mucosa. The posterior pharynx and tonsils may also be involved. Most disease occurs in the summer.
    • Patients may report anorexia, malaise, irritability, headache, backache, and diarrhea. Symptoms resolve in 3-4 days.
  • Hand-foot-and-mouth disease
    • This is mainly a disease of children; most patients are younger than 10 years. Epidemics of HFMD occur approximately every 3 years.
    • Coxsackievirus A16 is the most common etiologic agent, although enterovirus 71 and numerous other coxsackievirus serotypes may also cause the disease.
    • Following an incubation period of 3-6 days, patients experience prodromal symptoms such as fever, cough, sore throat, malaise, and anorexia. The prodrome lasts from 12-36 hours; afterward, vesicular eruptions of the hands, feet, and oral cavity develop. This may cause decreased oral intake in young children. The lesions self-resolve within 5-7 days.
    • Infection with enterovirus 71 may be accompanied by severe neurologic disease including encephalitis, meningitis, and poliolike paralysis.35
  • Encephalitis
    • Frank encephalitis is an unusual manifestation of enterovirus infection.36
    • Echovirus 9 is the most common etiologic agent.
    • Clinical manifestations have ranged from lethargy, drowsiness, and personality change to seizures, paresis, and coma. Children with focal encephalitis present with partial motor seizures, hemichorea, and acute cerebellar ataxia; this may mimic herpes simplex encephalitis.37,38
  • Nonpoliovirus paralytic disease
    • Enterovirus 71 and coxsackievirus A7 have been associated with large outbreaks of poliomyelitislike disease in Russia, Eastern Europe, Thailand, and Taiwan.33 Some cases have manifested as brainstem encephalitis or noncardiogenic pulmonary edema, with some having a fatal course.
    • Paralytic disease caused by nonpolioviruses other than enterovirus 71 is usually less severe and is associated with paralysis. It manifests as muscle weakness and complete unilateral oculomotor palsy.
    • Guillain-Barré syndrome and transverse myelitis has been reported in a small number of patients infected with coxsackievirus serotypes A2, A5, A9, and B4 and with echovirus serotypes 5, 6, and 22.39
  • Neonatal infections: Refer to the article Enteroviral Infections in eMedicine’s Pediatrics volume.

Physical

Physical examination findings in enteroviral disease vary greatly depending on the type of illness and etiologic agent.

  • Nonspecific febrile illness: Physical findings are those of general viral illness; mild pharyngeal erythema or conjunctivitis may be present.
  • Pleurodynia: Paroxysmal chest pain is characteristic, has no prodrome, and begins with an abrupt onset of spasmodic pain, typically over the lower part of the rib cage or the upper abdominal region. Fever often occurs within one hour of the onset of pain and subsides as the pain recedes. During paroxysms, respirations are rapid and shallow. The pain is reproducible, and patients appear healthy between paroxysms of pain. Auscultation may reveal a pleural friction rub.
  • Myopericarditis: The most common symptoms are dyspnea, chest pain, fever, and malaise.40 Pain in the precordial area maybe sharp or dull and is often exacerbated by the recumbency position. A pericardial friction rub is transient, if present. Signs of congestive heart failure are present in 20% of cases.41
  • AHC: The hallmark physical findings include ocular erythema and subconjunctival hemorrhage, which seems to be more profuse in young patients.42 Palpebral edema, chemosis, and ocular discharge may also be noted. Preauricular lymphadenopathy is an associated finding in AHC.
  • Aseptic meningitis: Meningeal signs (nuchal rigidity, bulging fontanelles in infants) may be present, along with a positive Kernig and/or Brudzinski sign. Some patients develop a rash. Adults may experience a more prolonged period of headache and fever than children.43 Approximately 5%-10% of infants with aseptic meningitis experience complications such as febrile seizures, complex seizures, lethargy, coma, and movement disorders early in the course.32
  • Encephalitis: Manifestations range from lethargy, drowsiness, and personality change to seizures, paresis, coma, motor seizures, hemichorea, and acute cerebellar ataxia.44
  • Herpangina: Examination of the oral mucosa reveals punctate macular lesions that evolve into vesicles and eventually ulcerate. The most common site of involvement is the anterior tonsillar pillar and soft palate (mimics pharyngitis or tonsillitis). The lesions are tender and subside within one week.
  • HFMD: Vesicular lesions develop on the hands and feet and in the oral cavity. Hands are involved more commonly than feet. The skin lesions consist of mixed papules. Clear vesicles appear gray and are surrounded by erythematous rings. Lesions are tender and resemble those of herpes simplex or varicella zoster infection. They resolve in approximately one week.
  • Poliomyelitis
    • Nonparalytic polio: Signs of meningeal irritation are present, and patients may have positive Kernig and Brudzinski signs. In infants, the head drop sign can be elicited.
    • Paralytic polio: In early-stage disease, reflexes are normally active. A change in the character of reflexes precedes paralysis by 12-24 hours. Superficial reflexes are the first to decrease, followed in 8-24 hours by loss of deep tendon reflexes. The resultant paralysis is flaccid and characteristically asymmetric in distribution. Proximal limb muscles are involved more than distal muscles. The lower extremities are affected more commonly than the upper extremities.
  • Orchitis: In some remote cases, the presentation of coxsackievirus B infection clinically resembles mumps orchitis.

Causes

  • The most common mode of transmission of enteroviruses is via the fecal-oral route. Poor sanitation, low socioeconomic status, and crowded living conditions all facilitate the spread of infection. Direct contact with feces occurs with activities such as diaper changing. Indirect transmission due to poor sanitary conditions may occur via numerous routes, including via contaminated water, food, fingers, fomites, or contaminated ophthalmological instruments (eg, AHC).
  • Respiratory-oral spread may also be the mode of transmission for coxsackievirus A21 and other coxsackievirus serotypes.
  • Transmission of enteroviruses has been described among travelers swimming in sewage-contaminated seawater.45

More on Enteroviruses

Overview: Enteroviruses
Differential Diagnoses & Workup: Enteroviruses
Treatment & Medication: Enteroviruses
Follow-up: Enteroviruses
References
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Further Reading

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Keywords

Enterovirus, enteroviral infections, Bornholm disease, Bornholm's disease, epidemic myalgia, Sylvest's disease, Sylvest disease, devil's grip, polio, poliovirus, coxsackievirus group A, coxsackievirus group B, echovirus, aseptic meningitis, poliomyelitis, viral heart disease, hand foot and mouth disease, hand-foot-and-mouth disease, HFM disease, hemorrhagic conjunctivitis, herpangina, pleurodynia, myocarditis, pericarditis, meningoencephalitis, common cold, aseptic meningitis, acute hemorrhagic conjunctivitis, AHC, viremia, myopericarditis, abortive polio, nonparalytic polio, paralytic polio

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Contributor Information and Disclosures

Author

Alexander Velazquez, MD, Fellow, Department of Infectious Diseases, Orlando Regional Medical Center
Alexander Velazquez, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Coauthor(s)

Mark R Wallace, MD, FACP, FIDSA, Clinical Professor of Medicine, Florida State University College of Medicine; Infectious Disease Fellowship Director, Orlando Regional Medical Center
Mark R Wallace, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Tropical Medicine and Hygiene, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Smeeta Sinha, MD, Staff Physician, Department of Dermatology, UMDNJ-New Jersey Medical School
Smeeta Sinha, MD is a member of the following medical societies: Alpha Omega Alpha, Phi Beta Kappa, and Sigma Xi
Disclosure: Nothing to disclose.

Rajendra Kapila, MD, MBBS, Professor of Medicine, Department of Medicine, UMDNJ, New Jersey Medical School
Rajendra Kapila, MD, MBBS is a member of the following medical societies: American College of Physicians, American Medical Association, Infectious Diseases Society of America, and Infectious Diseases Society of New Jersey
Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Pratibha Dua, MD, MBBS, Staff Physician, Department of Internal Medicine, The Brooklyn Hospital Center
Pratibha Dua, MD, MBBS is a member of the following medical societies: American Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Mary Nettleman, MD, MS, Chair, Department of Medicine, Michigan State University
Mary Nettleman, MD, MS is a member of the following medical societies: American College of Physicians, Association of Professors of Medicine, Central Society for Clinical Research, Infectious Diseases Society of America, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

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Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

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Ronald A Greenfield, MD, Professor, Department of Internal Medicine, Section of Infectious Diseases, University of Oklahoma College of Medicine
Ronald A Greenfield, MD is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Central Society for Clinical Research, Infectious Diseases Society of America, Medical Mycology Society of the Americas, Phi Beta Kappa, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology
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CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
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Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
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