eMedicine Specialties > Dermatology > Viral Infections

Monkeypox

Author: Mary Beth Graham, MD, Associate Professor, Department of Medicine, Division of Infectious Diseases, Medical College of Wisconsin
Coauthor(s): Juliet L Gunkel, MD, Assistant Professor, University of Wisconsin School of Medicine and Public Health; Consulting Physician, University of Wisconsin Hospital; Janet Fairley, MD, Professor and Head, Department of Dermatology, University of Iowa
Contributor Information and Disclosures

Updated: Oct 24, 2008

Introduction

Background

In 1970, when smallpox was nearly eradicated, a previously unrecognized orthopoxvirus named monkeypox was identified in humans. The first known human case occurred in the Equateur province of Zaire (now known as the Democratic Republic of Congo [DRC]) when a 9-year-old boy developed a smallpoxlike illness, which was eventually confirmed as human monkeypox by the World Health Organization.¹ Retrospectively, similar cases occurring in 1970-1971 from the Ivory Coast, Liberia, Nigeria, and Sierra Leone were attributed to monkeypox infection.

Monkeypox was limited to the rain forests of central and western Africa until 2003, when the first cases in the Western Hemisphere were reported. In late spring 2003, multiple persons were identified in the midwestern United States who had developed fever, rash, respiratory symptoms, and lymphadenopathy following exposure to ill pet prairie dogs (Cynomys species) infected with the monkeypox virus.²

Most confirmed cases reported direct contact or exposure to ill prairie dogs showing signs of profuse nasal discharge, ocular discharge, dyspnea, lymphadenopathy, and mucocutaneous lesions. Traceback investigators concluded that all confirmed cases of monkeypox were associated from a common animal distributor where prairie dogs were housed or transported with African rodents from Ghana. Among these rodents were Gambian rats, which are known reservoirs of monkeypox in their native habitat of Africa.

In this outbreak, imported asymptomatic animals transmitted a nonindigenous pathogen to an indigenous susceptible animal. After an average incubation period of 12 days, the animal became ill and was capable of transmitting the pathogen to humans when in close proximity. The potential for human-to-human transmission and human-to-animal transmission remains unknown.

The Medscape Emerging and Reemerging Infectious Diseases Resource Center may be of interest.

Pathophysiology

The monkeypox virus is a member of the genus orthopox (family Poxviridae); other members include cowpox, vaccinia, and variola (smallpox) viruses. It is a zoonotic virus with primary transmission believed to occur through direct contact with infected animals or possibly by ingestion of their inadequately cooked flesh. Inoculation may be from cutaneous or mucosal lesions on the animal, especially when the skin barrier is compromised secondary to bites, scratches, or other trauma. The infection was first seen in laboratory monkeys in 1958, thus, the name monkeypox, although rodents are believed to be the major reservoir in Africa.^3,4

Secondary, or human-to-human, disease transmission was found to be another possible route in an outbreak in the DRC in 1996-1997.⁴ Studies of this outbreak suggested that within households, monkeypox was secondarily transmitted to 8-15% of human contacts. Prior to this, monkeypox was not identified as an important worldwide health problem because human infection rates were not known to play a significant role in the pathogenesis. Analysis of the 2003 US outbreak implicates animal-to-animal and animal-to-human transmission as the significant route of transmission. However, in the 2003 US outbreak, clear exposure to an infected animal could not be identified in one case, and, therefore, human-to-human transmission could not be excluded.

Frequency

United States

No cases occurred in the United States until the late spring 2003 outbreak in the Midwestern states. Between May 16 and June 20, 2003, 71 suspected cases of monkeypox were investigated.⁵ A total of 47 individuals were identified with confirmed (n = 37) or probable (n = 10) monkeypox virus infection. Monkeypox cases were confirmed on the basis of virus isolation or detection of the virus by polymerase chain reaction (PCR) from a clinical specimen (eg, skin biopsy or throat culture). Individuals who presented with fever and rash within 21 days of exposure to monkeypox and had serum positive for orthopox immunoglobulin M (IgM), but did not have culture- or PCR-positive clinical specimens, were classified as having a probable case of infection.^6,7

International

This condition is rare and only known to be indigenous to the rain forests of western and central Africa. It was first recognized in humans in 1970 after the eradication of smallpox, possibly because of the subsequent unmasking of the infection. Surveillance reports from 1981-1986 documented 338 cases in the DRC (out of a 1982 estimated population of 5 million). In the 1996-1997 outbreak in the DRC, the attack rate was 22 cases per 1000 population.

Mortality/Morbidity

The disease in the United States was generally self-limited, with resolution in 2-4 weeks, depending on the severity of the illness. However, a small subset of patients, most commonly pediatric patients, had a more severe course, with several patients requiring ICU care.⁸

Complications reported from African outbreaks include pitted scars, deforming scars, secondary bacterial infection, bronchopneumonia, respiratory distress, keratitis, corneal ulceration, blindness, septicemia, and encephalitis.

Data from the African outbreaks suggest that prior smallpox vaccination confers 85% protection from monkeypox; infection may be milder even several years after vaccination, and the incidence of complications may be reduced.^9,10 With the recent US outbreak, the Centers for Disease Control and Prevention (CDC) recommended smallpox vaccination up to 2 weeks, ideally within 4 days, after a significant, unprotected exposure to a diseased animal or a confirmed human case.¹¹

African cases have mortality rates of 1-10%, with the highest rates occurring in children and individuals without vaccination. In general, the prognosis is related to the amount of exposure to the virus, host immune response, comorbidities, vaccination status, and severity of complications.

Genomic sequencing of US, western African, and central African monkeypox isolates have confirmed the existence of 2 distinct monkeypox clades. The isolates from the United States were identical to the western African isolates. The disease course for individuals infected with the western African isolates is milder with less human-to-human transmission than for those infected with isolates from central Africa.¹²

Sex

The incidence is equal in males and females.

Age

In the African epidemics, 90% of the patients were children younger than 15 years.¹³ In the recent US outbreak, of the confirmed cases in 2003 (n = 35), 11 patients were younger than 18 years and 24 were older.

Clinical

History

Monkeypox can cause a syndrome clinically similar to smallpox but overall is less infectious and less deadly.

• Transmission
  • Contact with ill animals or animal reservoirs from Western Africa (eg, prairie dogs, rabbits, rats, mice, squirrels, dormice, monkeys, porcupines, gazelles)
  • Preparing or ingesting infected animals
  • Direct cutaneous (skin-to-skin) or respiratory contact with an animal or person who is infected
• The incubation period averages 12 days, ranging from 4-20 days.
• Prodrome or preeruptive stage (lasts 1-10 d)
  • Fever is commonly the first symptom (usually 38.5-40.5°C).
  • The febrile illness is often accompanied by chills, drenching sweats, severe headache, backache, myalgia, malaise, anorexia, prostration, pharyngitis, shortness of breath, and cough (with or without sputum).
  • Lymphadenopathy appears within 2-3 days after the fever. In the 2003 outbreak, 47% of patients had nodes measuring several centimeters in diameter in the cervical and submental areas.
• Exanthem (eruptive) stage: Most persons develop a rash within 1-10 days after the onset of fever. The rash often starts on the face and then spreads to the rest of the body. It persists for 2-4 weeks until all lesions have shed the crusts.
• Encephalitis with IgM found in the cerebrospinal fluid has been reported.¹⁴

Physical

• The most reliable clinical sign differentiating monkeypox from smallpox and chickenpox is enlarged lymph nodes, especially the submental, submandibular, cervical, and inguinal nodes.
• Enanthema: Nonspecific lesions and inflammation of the pharyngeal, conjunctival, and genital mucosae have been observed.
• Exanthema
  • Within a particular body region, lesions evolve synchronously over 14-21 days, similar to the development of lesions with smallpox. However, unlike smallpox, skin lesions may appear in crops. In contrast to smallpox, the lesions do not have a strong centrifugal distribution.
  • Lesions progress from macules to papules to vesicles and pustules; umbilication, crusting, and desquamation follow. Most lesions are 3-15 mm in diameter.
  • The face, the trunk, the extremities, and the scalp are involved. Lesions appear in covered and uncovered areas.
  • Lesions may be seen on the palms and the soles.
  • Necrosis, petechiae, and ulceration may be features.
  • Pain is unusual, and, if it occurs, it is often associated with secondary bacterial infection. Pruritus may occur.
  • In patients who have been previously vaccinated against smallpox, a milder form of disease occurs. In children, the lesions may appear as nonspecific, erythematous papules that are 1-5 mm in diameter and suggestive of arthropod bite reactions. Subtle umbilication may be seen.
  • In the African outbreaks, 20% of unvaccinated patients developed a confluent, erythematous eruption on the face and the upper part of the trunk, which some authors have termed the septicemic rash of monkeypox.¹³
  • Hemorrhagic and flat forms, which can be seen with smallpox, have not been reported in patients with monkeypox.
  • Deep pock scars can result as the lesions resolve.

Causes

In the DRC in 1997, animals caught from the wild were tested for the monkeypox virus. The following animals were found to have neutralizing antibodies against the monkeypox virus, suggesting a role as natural reservoirs: domestic pig (Sus scrofa), Gambian rat (Cricetomys emini), elephant shrew (Petrodromus tetradactylus), Thomas's tree/rope squirrel (Funisciurus anerythrus), Kuhl's tree squirrel (Funisciurus congicus), and sun squirrel (Heliosciurus rufobrachium).⁴

Human-to-human transmission supplanted the prominence of animal-to-human transmission in the 1996-1997 outbreak in the DRC. Crowded living quarters, poor hygiene, discontinuation of the smallpox vaccination, and decreased herd immunity were implicated. Respiratory droplets and direct contact with mucocutaneous lesions or fomites have been postulated as routes of human-to-human transmission.

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