Patients suffering from MP present with clinical symptoms similar to those of smallpox. Upon query, they may report direct contact with rodents within three weeks previous to symptom onset. They may also state to have eaten such an animal. The average incubation period is less than two weeks and in some cases, only few days pass until first symptoms of an infection appear.

The prodromal stage of disease is characterized by flu-like symptoms, mainly fever of up to 40 °C, chills, sweats, malaise, headache, aching limbs and back, as well as myalgia. Severe lymphadenopathy may be a very striking symptom. It does mainly affect cervical and inguinal lymph nodes and may in fact serve to distinguish MP from smallpox, a disease associated with less severe lymphadenopathy. In some cases, patients show signs of an upper respiratory infection, suffer from pharyngitis, cough and dyspnea. This stage lasts approximately one week.

The prodromal stage is followed by the eruptive stage and patients now develop generalized rash. After first macules and papules appear on the face, rash usually spreads over the whole body. Pruritus may occur, but the condition is not painful. Papules rarely measure more than 1.5 cm in diameter. Unless a patient has been vaccinated against smallpox, papules turn into vesicles or pustules, break, dry and form crusts. In cases of uncomplicated MP, cutaneous lesions heal spontaneously after a few weeks, but scars may remain. Secondary bacterial infection may, however, change the clinical presentation, delay healing and aggravate the patient's overall condition.

Mucous membranes of all body regions may show unspecific signs of inflammation.

Involvement of other organ systems is rarely seen and may be limited to immunodeficient or otherwise more susceptible patients. In this context, a MP-associated encephalitis has been reported [10].

• Cervical Lymphadenopathy

  Other reported manifestations included cervical lymphadenopathy (69%), sore throat (63%), mouth ulcers (50%), cough (41%), and diarrhea (11%). [cdc.gov]

  Prior to, and concomitant with, rash development is the presence of maxillary, cervical, or inguinal lymphadenopathy (1–4 cm in diameter) in many patients (Figure 1 ). Enlarged lymph nodes are firm, tender, and sometimes painful. [doi.org]

• Fever

  The illness begins with: Fever Headache Muscle aches Backache Swollen lymph nodes Chills Exhaustion Within 1 to 3 days (sometimes longer) after the appearance of fever, the patient develops a rash, often beginning on the face then spreading to other parts [web.archive.org]

  Monkeypox virus begins with a fever, headache, muscle aches, backache, swollen lymph nodes, a general feeling of discomfort and exhaustion. [oakgov.com]

  Related: Central African Republic: No new cases of monkeypox Cape Verde: 7,000 Zika cases, No microcephaly Nigeria: Lassa fever deaths top 100, Benin death toll now 12 [outbreaknewstoday.com]

  Monkeypox has a clinical presentation very similar to that of ordinary forms of smallpox, including flulike symptoms, fever, malaise, back pain, headache, and characteristic rash. [ncbi.nlm.nih.gov]

• Lymphadenopathy

  Important epidemiologic and clinical differences exist between human monkeypox in the United States and in Africa, including sex distribution, case fatality, morphology of skin lesions, and associated lymphadenopathy. [ncbi.nlm.nih.gov]

  The main difference between symptoms of smallpox and monkeypox is that monkeypox causes lymph nodes to swell (lymphadenopathy) while smallpox does not. [web.archive.org]

• Fatigue

  The illness begins with a fever, chills, headache, muscle aches, backache, extreme fatigue, and, unlike smallpox, prominent swollen lymph nodes. About 1 to 3 days after the fever appears, a rash develops. [msdmanuals.com]

  An initial febrile prodrome is accompanied by generalized headache and fatigue. Prior to, and concomitant with, rash development is the presence of maxillary, cervical, or inguinal lymphadenopathy (1–4 cm in diameter) in many patients (Figure 1 ). [doi.org]

• High Fever

  It is mostly found in West and Central Africa; it begins with a high fever followed by a rash. The virus is also spread from person to person, especially a sick or dead person to another. [africanews.com]

  It is a potentially severe illness that begins with a high fever, followed by the development of a characteristic rash. [news-medical.net]

• Weakness

  Abstract Weak or nonexistent smallpox immunity in today's human population raises concerns about the possibility of natural or provoked genetic modifications leading to re-emergence of variola virus and other poxviruses. [ncbi.nlm.nih.gov]

  WHO considered the overall risk of this outbreak high at national level given the weak surveillance system coupled with the limited public health infrastructure. [doi.org]

• Cough

  Symptoms : The initial symptoms are fever, chills, sore throat, cough, headache, myalgias, blepharoconjunctivitis, and adenopathy. [bcbsma.medscape.com]

  Getty Images Europe) “The symptoms in human is similar to those seen in the past in smallpox patient although less severe - monkeypox should be suspected in any person with rash, fever, chills, sweats, headache backache, lymphadenopathy, sore-throats, cough [mirror.co.uk]

  Its clinical presentation in humans is similar to smallpox including fever; headache; cough; and a painful rash. It is caused by monkeypox virus and is usually transmitted to humans through bites or via contact with an animal's blood. [icd10data.com]

  During this prodrome phase the affected individual can experience fever, malaise and swollen lymph nodes, with possible occurrence of other symptoms such as sweats, headache, backache, shortness of breath, sore throat and cough. [news-medical.net]

• Pharyngitis

  In some cases, patients show signs of an upper respiratory infection, suffer from pharyngitis, cough and dyspnea. This stage lasts approximately one week. [symptoma.com]

  […] a second girl (3.5 years) with the same clinical signs died a few hours after her admission to the hospital in Pimu on 14 August; a third child, a boy 3.5 years old, died on 23 August with clinical features of generalized eruptions, conjunctivitis, pharyngitis [doi.org]

• Dyspnea

  In some cases, patients show signs of an upper respiratory infection, suffer from pharyngitis, cough and dyspnea. This stage lasts approximately one week. [symptoma.com]

  […] immunohistochemistry. www.cdc.gov/ncidod/monkeypox/casedefinition.htm ) and Wisconsin Division of Public Health Clinical description: Includes (1) fever; (2) other clinical features including chills, sweats, headache, backache, adenopathy, sore throat, dyspnea [bcbsma.medscape.com]

• Back Pain

  Monkeypox has a clinical presentation very similar to that of ordinary forms of smallpox, including flulike symptoms, fever, malaise, back pain, headache, and characteristic rash. [ncbi.nlm.nih.gov]

  Get answers on common health concerns, from back pain and allergies to migraines and stomach aches. Take the first step to finding care. Check your medical symptoms online to help determine your next move. [memoriallosbanos.org]

  […] bites) You can also get infected through indirect contact (contaminated materials and surfaces, respiratory particles) Geography Mostly central and western Africa Incubation Period 5 – 21 days Signs and Symptoms Phase One Headache Fever Chills Tiredness Back [drasatrust.org]

  The infection can be divided into two periods: the invasion period, during which symptoms include fever, intense headache, lymphadenopathy (swelling of the lymph node), back pain, myalgia (muscle aches), and an intense asthenia (lack of energy). [garda.com]

  The symptoms include headache, fever, back pains and in advanced cases, rashes bigger than those caused by chicken pox. [health.gov.ng]

• Myalgia

  The infection can be divided into two periods: the invasion period, during which symptoms include fever, intense headache, lymphadenopathy (swelling of the lymph node), back pain, myalgia (muscle aches), and an intense asthenia (lack of energy). [garda.com]

  Symptoms : The initial symptoms are fever, chills, sore throat, cough, headache, myalgias, blepharoconjunctivitis, and adenopathy. [bcbsma.medscape.com]

  The infection can be divided into two periods: the invasion period (0-5 days) characterized by fever, intense headache, lymphadenopathy (swelling of the lymph node), back pain, myalgia (muscle ache) and an intense asthenia (lack of energy); the skin eruption [who.int]

  The prodromal stage of disease is characterized by flu-like symptoms, mainly fever of up to 40 °C, chills, sweats, malaise, headache, aching limbs and back, as well as myalgia. Severe lymphadenopathy may be a very striking symptom. [symptoma.com]

• Skin Lesion

  Diagnostic testing by both polymerase chain reaction and culture revealed infectious monkeypox virus in skin lesions of all 3 patients; 2 patients had orthopoxvirus detected by immunohistochemistry in skin lesions. [ncbi.nlm.nih.gov]

• Skin Rash

  […] as "atypical chickenpox" and 6.1% among cases with skin rash for which clinical diagnosis could not be established. [ncbi.nlm.nih.gov]

  Those symptoms include fever, muscle aches and swollen lymph nodes, followed by a skin rash. They can normally be treated – monkeypox has a fatality rate of between one and 10 percent. [africatimes.com]

  "The monkey pox virus can cause an illness with the following symptoms; a generalized vesicular skin rash, fever, and painful jaw swelling," the body had said, urging people to maintain personal hygiene and avoid contacts with infected people. [dailysabah.com]

  The patient developed fever, muscle aches, chills and skin rash on 30 April. He reported that he had remained in his hotel room most of the time between 1 and 7 May. [who.int]

• Headache

  Monkeypox begins with fever, headache, muscle aches, and exhaustion. The main difference between symptoms of smallpox and monkeypox is that monkeypox causes lymph nodes to swell (lymphadenopathy) while smallpox does not. [web.archive.org]

  Monkeypox has a clinical presentation very similar to that of ordinary forms of smallpox, including flulike symptoms, fever, malaise, back pain, headache, and characteristic rash. [ncbi.nlm.nih.gov]

  Initial symptoms include fever, headache, aching muscles, backache, swollen lymph nodes, chills and exhaustion. A rash can also develop, usually starting on the face before spreading to other parts of the body. [theguardian.com]

  […] virus, and has been reported mainly in central and west African countries It can spread when someone is in close contact with an infected person, however there is a very low risk of transmission to the general population Initial symptoms include fever, headache [bbc.co.uk]

• Confusion

  She said there was confirmed transmission of varicella zoster virus and reports of measles transmission in the region and added that monkeypox is often confused with other rash illnesses. [medpagetoday.com]

  While Sievers' flight was en route to Midway, her mother confused Sievers' bug bites and the boy's pustules, and called her local hospital to ask what she should do to prepare to treat her daughter's symptoms. [articles.chicagotribune.com]

  Human monkeypox: confusion with chickenpox. Acta Trop. 1988 Dec; 45 (4):297–307. [ PubMed ] [ Google Scholar ] Articles from Emerging Infectious Diseases are provided here courtesy of Centers for Disease Control and Prevention [ncbi.nlm.nih.gov]

  Human monkeypox: confusion with chickenpox. Acta Trop. 45 : 297 -307. ↵ Mukinda, V. B., G. Mwema, M. Kilundu, D. L. Heyman, A. S. Khan, and J. J. Esposito. 1997. Re-emergence of human monkeypox in Zaire in 1996. [doi.org]

• Asthenia

  The infection can be divided into two periods: the invasion period, during which symptoms include fever, intense headache, lymphadenopathy (swelling of the lymph node), back pain, myalgia (muscle aches), and an intense asthenia (lack of energy). [garda.com]

  The infection can be divided into two periods: the invasion period (0-5 days) characterized by fever, intense headache, lymphadenopathy (swelling of the lymph node), back pain, myalgia (muscle ache) and an intense asthenia (lack of energy); the skin eruption [who.int]

An anamnesis revealing residence or stay in endemic regions, close contact to carriers or corresponding eating habits, as well as characteristic dermatological findings prompt a strong suspicion for monkeypox. However, this infectious disease is rare and diagnosis requires confirmation of the causative agent although smallpox has been eradicated. Samples, particularly fluid or crusts obtained from cutaneous lesions, may be evaluated electron microscopically. Detection of brick-shaped virus particles indicates an infection with Poxviridae, but does not allow for an identification of the species. The latter requires virus isolation and confirmation of the presence of monkeypox virus by molecular biological techniques like polymerase chain reaction [11]. Immunoassays may also be very helpful. To this end, an enzyme-linked immunosorbent assay has been developed by the US-American Centers for Disease Control and Prevention [12].

Of note, if biopsies are analyzed histopathologically, ballooning degeneration of keratinocytes, spongiosis, acanthosis and, in later stages, epidermic necrosis may be observed [13]. These findings are little specific.

Treatment is mainly supportive. Most MP patients suffer from mild symptoms that don't require specific interventions, but measures to prevent secondary bacterial infection and disease transmission to other people should be taken. In this context, the patient may receive antibiotic drugs and contact to fellow humans should be reduced. Dehydration may be an issue and can be corrected by intravenous administration of fluids.

Patients developing more severe forms of the disease may benefit from antiviral therapy. However, no controlled clinical trials have been carried out to confirm the effects of determined compounds in humans and possible side effects should be considered before deciding for such treatment. The efficacy of cidofovir has been shown in non-human primates [14]. Other compounds may be effective against monkeypox virus, too, but drug development is less advanced in these cases [15].

Prognosis is usually good or very good. In most cases, infection provokes only mild symptoms and is self-limiting. However, immunodeficient patients or those suffering from comorbidities may develop secondary bacterial infection and possibly fatal sepsis. The overall mortality is less than 3%.

The monkeypox virus, strictly speaking Orthopoxvirus simiae, is the causative agent of MP. This viral species pertains to the genus of Orthopoxvirus. Further representatives of this genus are those viruses provoking smallpox and cowpox as well as the vaccinia virus which has been used to elaborate vaccines for a long time [3]. Indeed, antigenic similarity between those viruses may confer immunity to those who have been immunized or infected with any other of the aforementioned species. The fact that an infection with cowpox prevented falling ill to smallpox was what started development of vaccines; patients vaccinated against smallpox are less susceptible to MP.

Orthopoxvirus have a characteristic brick-shaped form that may be recognized electron microscopically. Unfortunately, the similarity that provides cross-immunity also applies to morphology and thus does not allow for a distinction of species by this technique.

Monkeypox virus has been isolated from Gambian pouched rats (Cricetomys gambianus), African dormice (Graphiurus kelleni), Natal multimammate mice (Mastomys natalensis), tiny fat mice (Steatomys parvus), rope squirrels (Funisciurus spp.) and sun squirrels (Heliosciurus spp.) [4]. Thus, these species are currently considered the reservoir for monkeypox virus. Most likely, the list is not complete and future studies will demonstrate other rodents to carry the pathogen. Somewhat surprisingly, the virus has rarely been isolated from monkeys. It is named after these primates because the pathogen was first detected in laboratory monkeys.

The aforementioned rodents may transmit the virus by direct contact. Bites and scratches seem to increase the risk of infection. Also, some rodents serve as food sources and in this context, the pathogen may enter the human body either via mucous membranes of mouth, nose and eyes, or via the gastrointestinal tract. Human-to-human transmission has been estimated to account for approximately 10% of all MP cases. Here, sites of entry are probably the same as for zoonotic infections.

MP is a rare disease. Its causative agent is endemic only to tropical rain forests of Central and West Africa, with most cases reported in the Democratic Republic of the Congo. More recently, it has been detected in Sudan.

It was first described in humans in 1970 [5] and a few hundred infections have been registered in the 1980s. This sudden increase in MP incidence has been explained with cessation of smallpox vaccination in 1980, because immunization against the latter seems to provide certain immunity against MP [6]. Since then, sporadic infections as well as epidemics have been described. It has to be suspected that a significant share of cases is not even reported, though. Education of the general population and physicians is the key to avoidance of risky behavior and early detection of an infection [7].

Mortality is low and only few deaths have been related to MP. During early epidemics, mortality rates of up to 11% were reported for patients that had not been vaccinated against smallpox [8]. Regarding an outbreak in the Democratic Republic of the Congo during 1996 and 1997, 3.7% of affected patients died [2]. More recently, overall mortality has been estimated to be less than 3%.

Pediatric patients account for the majority of MP cases [8].

MP is a zoonotic disease caused by infection with the monkeypox virus. Little is known about the reservoir of the pathogen, about transmission between animals and to humans. It has been proposed that humans may contract the disease after being in close contact or eating an animal carrying the virus. Presumably, the virus may enter the human body via cutaneous lesions that may exist previously or result from bites and scratches, or via mucous membranes of the alimentary or upper respiratory tract. Living close to or working with rodents carrying the virus may lead to sub-clinical infections [9]. It is tempting to speculate that transmission between animals occurs similarly, but no studies have been conducted to this end.

Because rodents serve as a reservoir for the monkeypox virus, avoidance of direct or indirect contact largely contributes to prevention of MP. Also, such animals should not be eaten if other food sources are available.

Patients that suffer from MP should be isolated due to the risk of human-to-human transmission. Health care givers should wear protective clothing, gloves and masks when attending these people.

Monkeypox (MP) is a rare, zoonotic infectious disease whose etiologic agent is the monkeypox virus. This virus pertains to the genus of Orthopoxvirus.

Most cases of MP are reported in Central and West Africa, particularly in the Democratic Republic of the Congo. Here, people may contract the disease sporadically or during epidemics. Although MP has occasionally been diagnosed in other continents, epidemiological research could generally backtrack the source of infection to Africa [1].

The aforementioned parts of Africa are inhabited by various species of rodents that are assumed to serve as a reservoir for the causative virus. Presumably, people contract the disease after direct contact with animals that carry the virus. Bites seem to increase the probability of transmission. MP is mostly diagnosed in pediatric patients and this fact may either result from closer contact to animals or from an intrinsically increased susceptibility for the disease. Human-to-human transmission is possible but unlikely [2].

Clinically, MP is very similar to smallpox. Although MP is associated with a significantly lower mortality than smallpox, up to one fifth of all patients may still die. Cutaneous lesions, malaise and fever are the most frequently observed symptoms. They may not be distinguishable from smallpox or even varicella, especially if secondary bacterial infection complicates the patient's condition. Viral culture and molecular biological methods are the most specific techniques for diagnosing MP.

Treatment is mainly supportive and consists in wound care, therapy of secondary bacterial infection and antiviral drugs. Many infections are self-limiting. Of note, controlled clinical studies regarding treatment of MP have not been carried out. It has not been analyzed whether the restricted medical coverage in Central and West Africa contributes to MP-associated mortality or not.

Monkeypox (MP) is a rare, zoonotic infectious disease endemic to tropical rain forests of Central and West Africa and Sudan. It is caused by the monkeypox virus, a viral species pertaining to the same genus as those pathogens triggering smallpox and cowpox. The monkeypox virus is mainly transmitted by rodents that inhabit the aforementioned regions. Close contact is required to contract the disease. Of note, the disease has been diagnosed out of Africa after rodents had been caught here and shipped elsewhere.

Causes

Distinct species of rodents, namely rats, mice and squirrels, may transmit the etiologic agent upon close contact. Bites, scratches or other cutaneous lesions presumably increase the probability of infection. Some species that may harbor the virus serve as food sources and in this context, it may enter the human body either via mucous membranes of mouth, nose and eyes or via the gastrointestinal tract.

Human-to-human transmission is unlikely, but has been proven to happen.

Symptoms

MP typically manifests within two to three weeks after exposure to the pathogen. Initially, flu-like symptoms may be experienced, e.g., fever of up to 40 °C, chills, sweats, indisposition, headache, aching limbs, back and muscles. This stage of the disease may last for about a week before rash appears. Macules and papules develop on the face and subsequently spread to the whole body. Subsequently, they turn into vesicles, pustules, they break, dry, and form a crust that is finally shed. Healing occurs spontaneously. This whole process may take up to one month. While patients are suffering from cutaneous lesions, their lymph nodes may be significantly enlarged and tender.

Diagnosis

Diagnosis of MP requires confirmation of the presence of the causative agent. In order to achieve this, samples will be taken from skin lesions and analyzed applying molecular biological techniques or immunoassays. The main aim of diagnostic workup is to rule out differential diagnoses that may manifest similarly.

Treatment

There is no specific therapy for MP. Most patients suffer from mild symptoms and benefit from supportive care, i.e., prophylaxis or treatment of secondary bacterial infections and possible dehydration. If someone develops a more severe form of the disease, anti-viral drugs may be helpful. However, because MP is a rare disease, controlled clinical trial have not been carried out and anti-viral drugs may cause significant side effects.

1. Nalca A, Rimoin AW, Bavari S, Whitehouse CA. Reemergence of monkeypox: prevalence, diagnostics, and countermeasures. Clin Infect Dis. 2005; 41(12):1765-1771.
2. Hutin YJ, Williams RJ, Malfait P, et al. Outbreak of human monkeypox, Democratic Republic of Congo, 1996 to 1997. Emerg Infect Dis. 2001; 7(3):434-438.
3. Baker RO, Bray M, Huggins JW. Potential antiviral therapeutics for smallpox, monkeypox and other orthopoxvirus infections. Antiviral Res. 2003; 57(1-2):13-23.
4. Falendysz EA, Lopera JG, Lorenzsonn F, et al. Further Assessment of Monkeypox Virus Infection in Gambian Pouched Rats (Cricetomys gambianus) Using In Vivo Bioluminescent Imaging. PLoS Negl Trop Dis. 2015; 9(10):e0004130.
5. Ladnyj ID, Ziegler P, Kima E. A human infection caused by monkeypox virus in Basankusu Territory, Democratic Republic of the Congo. Bull World Health Organ. 1972; 46(5):593-597.
6. Reynolds MG, Damon IK. Outbreaks of human monkeypox after cessation of smallpox vaccination. Trends Microbiol. 2012; 20(2):80-87.
7. Reynolds MG, Emerson GL, Pukuta E, et al. Detection of human monkeypox in the Republic of the Congo following intensive community education. Am J Trop Med Hyg. 2013; 88(5):982-985.
8. Jezek Z, Szczeniowski M, Paluku KM, Mutombo M. Human monkeypox: clinical features of 282 patients. J Infect Dis. 1987; 156(2):293-298.
9. Reynolds MG, Carroll DS, Olson VA, et al. A silent enzootic of an orthopoxvirus in Ghana, West Africa: evidence for multi-species involvement in the absence of widespread human disease. Am J Trop Med Hyg. 2010; 82(4):746-754.
10. Sejvar JJ, Chowdary Y, Schomogyi M, et al. Human monkeypox infection: a family cluster in the midwestern United States. J Infect Dis. 2004; 190(10):1833-1840.
11. Olson VA, Laue T, Laker MT, et al. Real-time PCR system for detection of orthopoxviruses and simultaneous identification of smallpox virus. J Clin Microbiol. 2004; 42(5):1940-1946.
12. Karem KL, Reynolds M, Braden Z, et al. characterization of acute-phase humoral immunity to monkeypox: use of immunoglobulin M enzyme-linked immunosorbent assay for detection of monkeypox infection during the 2003 North American outbreak. Clin Diagn Lab Immunol. 2005; 12(7):867-872.
13. Bayer-Garner IB. Monkeypox virus: histologic, immunohistochemical and electron-microscopic findings. J Cutan Pathol. 2005; 32(1):28-34.
14. Stittelaar KJ, Neyts J, Naesens L, et al. Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection. Nature. 2006; 439(7077):745-748.
15. Sbrana E, Jordan R, Hruby DE, et al. Efficacy of the antipoxvirus compound ST-246 for treatment of severe orthopoxvirus infection. Am J Trop Med Hyg. 2007; 76(4):768-773.