A lecture by Dr. Naya Hassan about Monkeybox; which is a viral zoonotic infection that results in a rash similar to smallpox and started to spread around the world since May 2022.

1. Dr. Naya Hassan
Prof. Dr. Fouz Hassan
Prepared by:
Supervisor:
Dermatology Department
Tishreen University, Syria

2. Introduction
Monkeypox is a viral zoonotic infection that results in a rash similar to
smallpox. However, the person-to-person spread and the mortality from a
monkeypox infection are significantly lower than for smallpox.

3. Virology
Orthopoxvirus
Enveloped double‐stranded DNA virus with a genome size of
around 190 kb
first isolated in the late 1950s from a colony of sick monkeys.
The virus is in the same genus as variola and is used in
smallpox vaccine.
Two distinct strains of monkeypox exist in different
geographic regions of Africa:
Central Africa: more virulent.
Western Africa: less virulent and lacks a number of genes
present in the other viral strain.
Electron micrograph of
monkeypox virus

5. Epidemiology
Monkeypox was first identified as a cause of disease in humans in the
1970s in the Democratic Republic of the Congo.
The first outbreak of monkeypox in the Western Hemisphere occurred in
the United States in 2003.

6. Geographic Distribution
Since discontinuation of smallpox immunization, most cases have occurred
in Central and West Africa. However, sporadic cases have been reported in
several nonendemic countries, typically in returning travelers. In the
United States, an outbreak of monkeypox due to infected prairie dogs
exposed to imported animals from Africa occurred in 2003
in May 2022, multiple clusters of monkeypox were reported in Europe,
including Portugal, Spain, and the United Kingdom (UK) high (close contact
with infectious skin lesions during sex may be the most likely
mode of transmission).

8. Transmission
Animal-to-human transmission:
The virus is typically acquired through contact with an
infected animal's bodily fluids or through a bite.
Monkeys and humans are incidental hosts.
Reservoir remains unknown but is likely to be rodents.
Infected rodents from Western Africa were accidentally
imported into the United States; this led to the first
human monkeypox infections in the Western
Hemisphere.

9. Transmission
Human-to-human transmission:
Through large respiratory droplets.
Close contact with infectious skin lesions or from contact with lesion
material.
For droplet transmission, prolonged face-to-face contact may be required
for transmission to occur (eg, within a six-foot radius for ≥3 hours in the
absence of personal protection equipment [PPE])
In general, transmissibility from person to person is very low.
However, in a cluster of cases seen in May 2022, the risk of person-to-
person transmission appears to be high.

10. Incubation Period
Persons with a history of an animal bite
or scratch may have a shorter incubation
period than those with tactile exposures
(13 versus 9 days, respectively).

11. Clinical Manifestations
The predominant signs and symptoms are:
•Rash (97%)
•Fever (85%)
•Chills (71%)
•Lymphadenopathy (71%)
•Headache (65%)
•Myalgias (56%)

12. Clinical Manifestations
•The rash usually begins as macules and papules then progresses over a
two- to four-week period to vesicles, pustules, followed by umbilication,
scabbing, and desquamation.
•It starts on the trunk and then spreads to involve the palms and soles.
•Lesions can also involve the mucous membranes
•It ranges from 0.5 to 1 centimeter in size.
•Some patients develop only a localized rash on their hands associated
with direct contact with the infected animal.
Skin rash:

13. Clinical Manifistations

14. Clinical Manifestations
The onset of fever preceded the rash by approximately two days, but the
median duration of fever is shorter than the rash (8 and 12 days,
respectively).
Hospitalization was due a variety of reasons, including nausea, vomiting,
and dysphagia.
All of the patients in the United States outbreak survived with supportive
therapy; no antiviral therapy was administered.

15. Cluster of cases reported in May 2022:
It was noted that some patients may present with proctitis
or with lesions located on the genital or perianal area alone.

18. Diagnosis
•Although clinical features are helpful in making the diagnosis, laboratory
confirmation of monkeypox virus is necessary to differentiate this disease
from those caused by other potential etiologies.
•This includes: virus isolation (in mammalian cell cultures), electron
microscopy, real-time polymerase chain reaction (PCR), enzyme-linked
immunosorbent assay (ELISA), and immunofluorescent antibody assay.
•If the diagnosis of monkeypox is being considered, local and state public
health officials should be notified so that the samples are quickly
processed.
•Characteristic brick-shaped poxvirus virions are found on electron
microscopy.

19. Diagnosis
Electron Microscope

20. Diagnosis
Histopathologic analysis may demonstrate
ballooning degeneration of keratinocytes,
prominent spongiosis, dermal edema, and
acute inflammation; however these findings
can also be seen in other viral infections.
This figure shows large multinucleated cells
and eosinophilic viral inclusion bodies may be
seen in sections of the epidermis (Patient had
a primary lesion at the site of a previous cat
scratch.)

21. Differential Diagnosis
Given the worldwide eradication of smallpox, the most likely diagnostic consideration is varicella
(chickenpox). Unlike varicella where vesicular lesions are characteristically in different stages of
development and healing when the patient is examined, monkeypox lesions are all generally at
the same stage.
Because of concerns regarding bioterrorism, it is also important to consider the possibility of
smallpox in the differential diagnosis of a patient who has not been in the rain forests of Africa or
exposed to potentially infected animals. Lymphadenopathy, which has been observed in the
majority of unvaccinated patients, is a key distinguishing feature of monkeypox.
Lymphadenopathy can occur in the submandibular, cervical, or inguinal regions.
Also in the differential diagnosis is tanapox, another African poxvirus that causes a febrile
prodrome and skin lesions that resolve over several weeks without sequelae.
Orf and bovine stomatitis (also caused by parapoxviruses) can produce localized skin lesions
similar to those of monkeypox, but can be differentiated by an experienced microscopist by
morphologic features on electron microscopy. Parapoxvirions are slightly smaller than
orthopoxvirus virions and have a more regular surface pattern than orthopoxviruses.

22. Differential Diagnosis

23. Smallpox
Monkeypox

24. Lymphadenopathy
in monkeypox

25. Electron microscope
Orthopoxvirus
Parapoxvirus

26. Management
Supportive care:
Most patients have mild disease and recover without medical intervention.
Others who have risk factors for dehydration (eg, nausea, vomiting,
dysphagia) may require a short hospital stay for intravenous hydration.
For the seriously ill patient, supportive care is necessary until the patient
recovers from the infection.
Antivirals:
In general, tecovirimat is the treatment of choice, though some experts
may use dual therapy with tecovirimat and brincidofovir in patients with
severe disease.

27. Antivirals
Tecovirimat — In July 2018, tecovirimat was approved for use in the United States for
treatment of smallpox . Tecovirimat is a potent inhibitor of an orthopoxvirus protein
required for the formation of an infectious virus particle that is essential for
dissemination within an infected host.
The recommended dose of tecovirimat depends upon the patient's weight.. The
duration of treatment is 14 days. The most frequently reported side effects are
headache, nausea, and abdominal pain.
Brincidofovir — In June 2021, brincidofovir was approved for use in the United States
for treatment of smallpox. Brincidofovir is an analog of cidofovir that can be given
orally.
Cidofovir — has in vitro activity against monkeypox and has been shown to be effective
against lethal challenge in animal models. However, there are no clinical data regarding
its efficacy against monkeypox infection in humans and its use can be associated with
significant adverse events, including nephrotoxicity.

28. Complications
Bacterial superinfection of skin
Permanent skin scarring
Hyperpigmentation or hypopigmentation
Permanent corneal scarring (vision loss)
Pneumonia
Dehydration (vomiting, diarrhea, decreased oral intake due to painful
oral lesions, and insensible fluid loss from widespread skin disruption)
Sepsis
Encephalitis
Death

29. MRI showing areas of increased signal in the left thalamus (open star) and
right posterior parietal cortex (solid star) from a patient with monkeypox
encephalitis at day 3 after onset.

30. Mortality
In Central Africa, the fatality rate is approximately 10 percent and deaths
generally occur in the second week of illness.
In contrast, there were no deaths in the outbreak in the United States.
These more favorable outcomes in the United States may be related to a
healthier patient population, greater availability of supportive medical
care, and a less virulent strain of monkeypox, which was imported from
the West African nation of Ghana.
10%

31. Prevention
Smallpox vaccine:
It has a protective effect against acquisition of monkeypox virus and may
ameliorate the clinical manifestations.
the Centers for Disease Control and Prevention (CDC) recommended
vaccination with vaccinia virus for the limited number of individuals
exposed to monkeypox in the 2003 United States outbreak.
Vaccinia immune globulin:
In immunosuppressed patients with an exposure history, since
immunization with vaccinia virus vaccine is contraindicated.

32. Prevention
Infection control precautions:
Using both contact and airborne precautions are recommended for any
generalized vesicular rash of unknown etiology in which monkeypox and
smallpox are included in the differential diagnosis.

33. More research is needed!

34. References
Multi-country monkeypox outbreak in non-endemic countries, World Health Orgazation
[WHO].
Multi-country monkeypox outbreak: situation update . [Updated 10 June 2022] World
Health Orgazation [WHO].
Moore M, Zahra F. Monkeypox. [Updated 2022 May 22]. In: StatPearls [Internet]. Treasure
Island (FL): StatPearls Publishing; 2022 Jan.
Tyler KL. Emerging Viral Infections of the Central Nervous System: Part 2. Arch Neurol.
2009;66(9):1065–1074.
UpToDate.
Medscape.
Centers for Disease Control and Prevention [CDC].