fbpx

Monkeypox

Updated : February 22, 2024





Background

Monkeypox is a viral disease that infects humans and other mammals and causes smallpox-like cutaneous manifestations like rash and blisters and is caused by a virus from the Poxviridae family. It is an emerging zoonotic disease found in areas where smallpox has been eradicated.

The natural host of the virus remains uncertain. However, it has been identified in wild animals such as the rope squirrel and sooty mangabey. The incubation period of monkeypox is approximately 12 days in humans through human-to-human transmission.

The virus can be transmitted through various routes, including respiratory secretions and saliva, direct contact with the lesion or its exudates, and feces. It is important to note that the exact mode of transmission and the natural host of the virus is still being studied, and more research is needed to understand and prevent the spread of monkeypox.

Epidemiology

Monkeypox is a viral illness that affects both humans and certain species of animals. It was first identified in humans in 1970 in the Democratic Republic of the Congo and Asian monkeys in 1958 in Denmark during polio vaccine research. There are two strains of the virus, with the Congo Basin clade being more severe and having a higher death rate compared to the West African clade.

Many African countries, including Benin, Cameroon, Ghana, Liberia, Nigeria, and Sierra Leone, are endemic for monkeypox. However, the actual impact of the disease on public health is unknown. The first recorded instance of monkeypox outside of Africa was in 2003 in the United States when prairie dogs were infected by imported Gambian giant rats from Ghana, leading to 53 human cases.

In 2005, another outbreak in Sudan marked the second time the disease was reported outside of endemic African regions. Nigeria reported 122 cases of monkeypox in 2017, which was the first known occurrence in 39 years, with evidence of both zoonotic and human-to-human transmission. Monkeypox outbreaks are typically linked to individuals recently traveling from endemic areas.

However, in May 2022, the World Health Organization reported a new outbreak that was different from previous ones, involving over 780 laboratory-confirmed cases in 27 non-endemic countries without any travel history to endemic areas. This highlights the potential global spread of the disease and the need for continued monitoring and control efforts.

Anatomy

 

 

Pathophysiology

The transmission cycle of the monkeypox virus begins with the virus infecting the respiratory system. The virus then spreads through the lymphatic system to infect major organs and replicate, leading to primary viremia. During this stage, little to no virus is detectable in the blood as the body’s reticuloendothelial system efficiently removes it.

However, secondary viremia occurs when the virus is released from the infected organs and lymphoid tissues into the blood, reaching the skin’s cornified layer and causing a rash, as well as the mucosal epithelium and causing mucosal lesions. The severity of the rash and mucosal lesions depends on the amount of virus in the bloodstream during secondary viremia.

In the US, patients with monkeypox infection who reported symptoms of mucosal and gastrointestinal issues required volume replacement due to gastrointestinal fluid loss. This was because the fluid moved from the intravascular compartment to the extravascular compartment, causing hypoalbuminemia and fluid loss in the gastrointestinal tract.

This highlights that the monkeypox infection results in systemic compromise, with complications not limited to the mucosal and integumentary surfaces, as indicated by the overall clinical presentation of the disease.

Etiology

The Monkeypox virus (MPXV) belongs to the Orthopoxvirus genus, which includes cowpox, variola, and vaccinia virus. It is a double-stranded DNA virus with an oval or brick-shaped structure, a lipoprotein envelope, and a genome similar to other viruses in its genus. The MPXV genome consists of a 6379-base pair terminal inverted repetition with a telomere resolution sequence and short tandem repeats. The virus infects host cells through either fusion of the viral envelope with host cell plasma membrane receptors or endosomal uptake through macropinocytosis.

Once inside the host cell, the virus impairs the cellular defense mechanisms and stimulates early gene expression leading to DNA replication and the production of intermediate transcription factors. Two different phylogenetic clades of MPXV have been identified in the literature, the Central African clade and the West African clade. The Central African clade is considered to be more virulent than the West African clade due to differences in its genomic structure.

This increased virulence results from the inhibition of T cell activation and the production of important immune system cytokines like interferon-gamma and tissue necrosis factor-alpha. The Central African clade also has a gene that inhibits complement enzymes, further contributing to its increased virulence. However, MPXV’s virulence does not involve the inhibition of significant histocompatibility complex expression or the cellular transport of MHC molecules.

Genetics

 

 

Prognostic Factors

The prognosis of monkeypox varies and can range from mild to severe. Factors that may affect the prognosis of monkeypox include age, overall health, and prompt access to medical care. Individuals infected with the virus recover without complication, while few may experience severe symptoms, such as high fever, skin rashes, and neurological problems.

The monkeypox virus has two different clades. The West African clade has a better prognosis, with a case fatality rate of less than 1%. The Central African clade is fatal, with up to 11% case fatality rate in unvaccinated children. Aside from possible scarring and skin discoloration, most patients recover completely within four weeks from the onset of symptoms.

Clinical History

Clinical History

Monkeypox is a viral illness that shares many clinical features with smallpox. However, it has some distinctive characteristics that differentiate it from smallpox. One of the most notable of these is the early onset of fever and pronounced lymphadenopathy. Almost 90% of individuals with monkeypox exhibit swollen lymph nodes, which can be located in various regions of the body, including the submandibular, cervical, postauricular, axillary, or inguinal areas.

These nodes can be firm, tender, and sometimes painful, with a size of approximately 1 to 4 cm. The course of monkeypox is generally milder than that of smallpox. Common symptoms reported by patients during outbreaks of monkeypox include rash, fever, chills, headache, myalgia, and swollen lymph nodes.

Some patients also experience symptoms such as tonsillitis, pharyngitis, coughing, nausea, and vomiting (which can cause severe dehydration). The average duration of the fever is 8 days, and the average duration of the rash is 12 days, with a 2-day gap between the onset of the fever and the onset of the rash. However, in some cases, the gap can be as long as 12 days.

 

 

 

Physical Examination

Physical Examination

Human monkeypox is characterized by the appearance of a rash about one to three weeks after the onset of fever and swelling of the lymph nodes. The rash is monomorphic and has a centrifugal distribution, starting as macular and evolving through papular, pustular, and vesicular stages, ultimately ending with scabbing and desquamation. The lesions of monkeypox infection are well-defined and have deep and hard characteristics with an umbilicated appearance.

The progression of the rash is slow, and the lesions are at a similar stage of development throughout the body. The number of lesions reported throughout the rash phase can range from a few to thousands, and some may be in the oral cavity, causing difficulties with eating and drinking. The range of the lesions is estimated to be about 0.5 to 1 cm in diameter. A small number of lesions may be ulcerated, necrotic, and few may have hemorrhagic pustules.

Individuals infected with human monkeypox may experience various complications, including dehydration, respiratory distress, bronchopneumonia, secondary bacterial infections, gastrointestinal issues, sepsis, corneal infections leading to vision loss, and encephalitis. The risk of complications is higher in unvaccinated individuals (74%) compared to those who have been vaccinated (39.5%). The duration of the illness is usually around four weeks.

Individuals with prior smallpox vaccination may experience a milder form of the illness, characterized by a pleomorphic rash and lymphadenopathy in roughly half of the cases, with no reported deaths. Post-infection scarring is a common long-term consequence for individuals who survive the illness.

 

 

 

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Differential Diagnoses

  • Smallpox
  • Chickenpox
  • Eczema herpeticum
  • Disseminated herpes simplex.
  • Drug-associated eruption
  • Syphilis
  • Disseminated zoster.
  • Generalized vaccinia.

 

 

 

Laboratory Studies

 

 

 

Imaging Studies

 

 

 

Procedures

 

 

 

Histologic Findings

 

 

 

Staging

 

 

 

Treatment Paradigm

Presently, there is no FDA-approved treatment for monkeypox. The disease is typically mild and self-limiting for those who experience symptoms such as pain, fever, or secondary infections. However, some precautions may be taken to avoid an epidemic. Until all lesion crusts have naturally come off and a new skin layer has grown, the infected person should stay in isolation, wear a protective mask, and have lesions covered as much as possible.

Supportive care such as pain relief and antibiotics can be provided. However, for individuals with weakened immune systems, pregnant women, and children, specialized treatment may be necessary. Antiviral medications and vaccines that were originally developed for smallpox have shown promise in treating monkeypox due to the similarities between the viruses.

Tecovirimat, an antiviral drug, has been approved by both the FDA and the EMA for the treatment of smallpox and can be used to treat monkeypox. Other antiviral drugs, such as cidofovir and brincidofovir, may also be used for treatment. Additionally, VIGIV, an immunoglobulin used to treat complications from vaccinia vaccination, can be used for monkeypox treatment through the expanded access protocol of the US Centers for Disease Control and Prevention.

 

 

 

by Stage

 

 

 

by Modality

 

 

 

Chemotherapy

 

 

 

Radiation Therapy

 

 

 

Surgical Interventions

 

 

 

Hormone Therapy

 

 

 

Immunotherapy

 

 

 

Hyperthermia

 

 

 

Photodynamic Therapy

 

 

 

Stem Cell Transplant

 

 

 

Targeted Therapy

 

 

 

Palliative Care

 

 

 

Medication

 

 

 

 

smallpox and monkeypox vaccine (live nonreplicating) (US Availability limited to health department CDC expanded access protocol) (Rx)

Postexposure prophylaxis:

0.5

ml

Subcutaneous (SC)

, 2 doses separated by 4 weeks
Note: For better efficacy administer within 4 days of exposure
If administered after 4 to 14 days, it may reduce the symptoms but may not prevent the disease



tecovirimat 

(Off-label)
Used for randomized clinical trial
Oral-
For 40 to less than 120 kg: 120 mg orally every 12 hours
For more than 120 kg: 600 mg orally every 8 hours
Intravenous-
For 35 to 120 kg: 200 mg intravenously every 12 hours



 

tecovirimat 

(Off-label)
Used for randomized clinical trial
Oral-
For 40 to less than 120 kg: 120 mg orally every 12 hours
For more than 120 kg: 600 mg orally every 8 hours
Intravenous-
For 35 to 120 kg: 200 mg intravenously every 12 hours
For >120 kg: 300 mg intravenously every 12 hours



 

Media Gallary

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870502/

https://www.ncbi.nlm.nih.gov/books/NBK574519/

 

 

Monkeypox

Updated : February 22, 2024




Monkeypox is a viral disease that infects humans and other mammals and causes smallpox-like cutaneous manifestations like rash and blisters and is caused by a virus from the Poxviridae family. It is an emerging zoonotic disease found in areas where smallpox has been eradicated.

The natural host of the virus remains uncertain. However, it has been identified in wild animals such as the rope squirrel and sooty mangabey. The incubation period of monkeypox is approximately 12 days in humans through human-to-human transmission.

The virus can be transmitted through various routes, including respiratory secretions and saliva, direct contact with the lesion or its exudates, and feces. It is important to note that the exact mode of transmission and the natural host of the virus is still being studied, and more research is needed to understand and prevent the spread of monkeypox.

Monkeypox is a viral illness that affects both humans and certain species of animals. It was first identified in humans in 1970 in the Democratic Republic of the Congo and Asian monkeys in 1958 in Denmark during polio vaccine research. There are two strains of the virus, with the Congo Basin clade being more severe and having a higher death rate compared to the West African clade.

Many African countries, including Benin, Cameroon, Ghana, Liberia, Nigeria, and Sierra Leone, are endemic for monkeypox. However, the actual impact of the disease on public health is unknown. The first recorded instance of monkeypox outside of Africa was in 2003 in the United States when prairie dogs were infected by imported Gambian giant rats from Ghana, leading to 53 human cases.

In 2005, another outbreak in Sudan marked the second time the disease was reported outside of endemic African regions. Nigeria reported 122 cases of monkeypox in 2017, which was the first known occurrence in 39 years, with evidence of both zoonotic and human-to-human transmission. Monkeypox outbreaks are typically linked to individuals recently traveling from endemic areas.

However, in May 2022, the World Health Organization reported a new outbreak that was different from previous ones, involving over 780 laboratory-confirmed cases in 27 non-endemic countries without any travel history to endemic areas. This highlights the potential global spread of the disease and the need for continued monitoring and control efforts.

 

 

The transmission cycle of the monkeypox virus begins with the virus infecting the respiratory system. The virus then spreads through the lymphatic system to infect major organs and replicate, leading to primary viremia. During this stage, little to no virus is detectable in the blood as the body’s reticuloendothelial system efficiently removes it.

However, secondary viremia occurs when the virus is released from the infected organs and lymphoid tissues into the blood, reaching the skin’s cornified layer and causing a rash, as well as the mucosal epithelium and causing mucosal lesions. The severity of the rash and mucosal lesions depends on the amount of virus in the bloodstream during secondary viremia.

In the US, patients with monkeypox infection who reported symptoms of mucosal and gastrointestinal issues required volume replacement due to gastrointestinal fluid loss. This was because the fluid moved from the intravascular compartment to the extravascular compartment, causing hypoalbuminemia and fluid loss in the gastrointestinal tract.

This highlights that the monkeypox infection results in systemic compromise, with complications not limited to the mucosal and integumentary surfaces, as indicated by the overall clinical presentation of the disease.

The Monkeypox virus (MPXV) belongs to the Orthopoxvirus genus, which includes cowpox, variola, and vaccinia virus. It is a double-stranded DNA virus with an oval or brick-shaped structure, a lipoprotein envelope, and a genome similar to other viruses in its genus. The MPXV genome consists of a 6379-base pair terminal inverted repetition with a telomere resolution sequence and short tandem repeats. The virus infects host cells through either fusion of the viral envelope with host cell plasma membrane receptors or endosomal uptake through macropinocytosis.

Once inside the host cell, the virus impairs the cellular defense mechanisms and stimulates early gene expression leading to DNA replication and the production of intermediate transcription factors. Two different phylogenetic clades of MPXV have been identified in the literature, the Central African clade and the West African clade. The Central African clade is considered to be more virulent than the West African clade due to differences in its genomic structure.

This increased virulence results from the inhibition of T cell activation and the production of important immune system cytokines like interferon-gamma and tissue necrosis factor-alpha. The Central African clade also has a gene that inhibits complement enzymes, further contributing to its increased virulence. However, MPXV’s virulence does not involve the inhibition of significant histocompatibility complex expression or the cellular transport of MHC molecules.

 

 

The prognosis of monkeypox varies and can range from mild to severe. Factors that may affect the prognosis of monkeypox include age, overall health, and prompt access to medical care. Individuals infected with the virus recover without complication, while few may experience severe symptoms, such as high fever, skin rashes, and neurological problems.

The monkeypox virus has two different clades. The West African clade has a better prognosis, with a case fatality rate of less than 1%. The Central African clade is fatal, with up to 11% case fatality rate in unvaccinated children. Aside from possible scarring and skin discoloration, most patients recover completely within four weeks from the onset of symptoms.

Clinical History

Monkeypox is a viral illness that shares many clinical features with smallpox. However, it has some distinctive characteristics that differentiate it from smallpox. One of the most notable of these is the early onset of fever and pronounced lymphadenopathy. Almost 90% of individuals with monkeypox exhibit swollen lymph nodes, which can be located in various regions of the body, including the submandibular, cervical, postauricular, axillary, or inguinal areas.

These nodes can be firm, tender, and sometimes painful, with a size of approximately 1 to 4 cm. The course of monkeypox is generally milder than that of smallpox. Common symptoms reported by patients during outbreaks of monkeypox include rash, fever, chills, headache, myalgia, and swollen lymph nodes.

Some patients also experience symptoms such as tonsillitis, pharyngitis, coughing, nausea, and vomiting (which can cause severe dehydration). The average duration of the fever is 8 days, and the average duration of the rash is 12 days, with a 2-day gap between the onset of the fever and the onset of the rash. However, in some cases, the gap can be as long as 12 days.

 

 

 

Physical Examination

Human monkeypox is characterized by the appearance of a rash about one to three weeks after the onset of fever and swelling of the lymph nodes. The rash is monomorphic and has a centrifugal distribution, starting as macular and evolving through papular, pustular, and vesicular stages, ultimately ending with scabbing and desquamation. The lesions of monkeypox infection are well-defined and have deep and hard characteristics with an umbilicated appearance.

The progression of the rash is slow, and the lesions are at a similar stage of development throughout the body. The number of lesions reported throughout the rash phase can range from a few to thousands, and some may be in the oral cavity, causing difficulties with eating and drinking. The range of the lesions is estimated to be about 0.5 to 1 cm in diameter. A small number of lesions may be ulcerated, necrotic, and few may have hemorrhagic pustules.

Individuals infected with human monkeypox may experience various complications, including dehydration, respiratory distress, bronchopneumonia, secondary bacterial infections, gastrointestinal issues, sepsis, corneal infections leading to vision loss, and encephalitis. The risk of complications is higher in unvaccinated individuals (74%) compared to those who have been vaccinated (39.5%). The duration of the illness is usually around four weeks.

Individuals with prior smallpox vaccination may experience a milder form of the illness, characterized by a pleomorphic rash and lymphadenopathy in roughly half of the cases, with no reported deaths. Post-infection scarring is a common long-term consequence for individuals who survive the illness.

 

 

 

Differential Diagnoses

  • Smallpox
  • Chickenpox
  • Eczema herpeticum
  • Disseminated herpes simplex.
  • Drug-associated eruption
  • Syphilis
  • Disseminated zoster.
  • Generalized vaccinia.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Presently, there is no FDA-approved treatment for monkeypox. The disease is typically mild and self-limiting for those who experience symptoms such as pain, fever, or secondary infections. However, some precautions may be taken to avoid an epidemic. Until all lesion crusts have naturally come off and a new skin layer has grown, the infected person should stay in isolation, wear a protective mask, and have lesions covered as much as possible.

Supportive care such as pain relief and antibiotics can be provided. However, for individuals with weakened immune systems, pregnant women, and children, specialized treatment may be necessary. Antiviral medications and vaccines that were originally developed for smallpox have shown promise in treating monkeypox due to the similarities between the viruses.

Tecovirimat, an antiviral drug, has been approved by both the FDA and the EMA for the treatment of smallpox and can be used to treat monkeypox. Other antiviral drugs, such as cidofovir and brincidofovir, may also be used for treatment. Additionally, VIGIV, an immunoglobulin used to treat complications from vaccinia vaccination, can be used for monkeypox treatment through the expanded access protocol of the US Centers for Disease Control and Prevention.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

smallpox and monkeypox vaccine (live nonreplicating) (US Availability limited to health department CDC expanded access protocol) (Rx)

Postexposure prophylaxis:

0.5

ml

Subcutaneous (SC)

, 2 doses separated by 4 weeks
Note: For better efficacy administer within 4 days of exposure
If administered after 4 to 14 days, it may reduce the symptoms but may not prevent the disease



tecovirimat 

(Off-label)
Used for randomized clinical trial
Oral-
For 40 to less than 120 kg: 120 mg orally every 12 hours
For more than 120 kg: 600 mg orally every 8 hours
Intravenous-
For 35 to 120 kg: 200 mg intravenously every 12 hours



tecovirimat 

(Off-label)
Used for randomized clinical trial
Oral-
For 40 to less than 120 kg: 120 mg orally every 12 hours
For more than 120 kg: 600 mg orally every 8 hours
Intravenous-
For 35 to 120 kg: 200 mg intravenously every 12 hours
For >120 kg: 300 mg intravenously every 12 hours



 

 

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870502/

https://www.ncbi.nlm.nih.gov/books/NBK574519/