Currently, there is no proven, safe treatment for monkeypox. The people who have been infected can be vaccinated up to 14 days after exposure.

Vaccination against smallpox is assumed to provide protection against human monkeypox infection considering they are closely related viruses and the vaccine protects animals from experimental lethal monkeypox challenge. This has not been conclusively demonstrated in humans because routine smallpox vaccination was discontinued following the apparent eradication of smallpox and due to safety concerns with the vaccine.

Smallpox vaccine has been reported to reduce the risk of monkeypox among previously vaccinated persons in Africa. The decrease in immunity to poxviruses in exposed populations is a factor in the prevalence of monkeypox. It is attributed both to waning cross-protective immunity among those vaccinated before 1980 when mass smallpox vaccinations were discontinued, and to the gradually increasing proportion of unvaccinated individuals. The United States Centers for Disease Control and Prevention (CDC) recommends that persons investigating monkeypox outbreaks and involved in caring for infected individuals or animals should receive a smallpox vaccination to protect against monkeypox. Persons who have had close or intimate contact with individuals or animals confirmed to have monkeypox should also be vaccinated.

CDC does not recommend preexposure vaccination for unexposed veterinarians, veterinary staff, or animal control officers, unless such persons are involved in field investigations.

The overall case-fatality rate for ordinary-type smallpox is about 30 percent, but varies by pock distribution: ordinary type-confluent is fatal about 50–75 percent of the time, ordinary-type semi-confluent about 25–50 percent of the time, in cases where the rash is discrete the case-fatality rate is less than 10 percent. The overall fatality rate for children younger than 1 year of age is 40–50 percent. Hemorrhagic and flat types have the highest fatality rates. The fatality rate for flat-type is 90 percent or greater and nearly 100 percent is observed in cases of hemorrhagic smallpox. The case-fatality rate for variola minor is 1 percent or less. There is no evidence of chronic or recurrent infection with variola virus.

In fatal cases of ordinary smallpox, death usually occurs between the tenth and sixteenth days of the illness. The cause of death from smallpox is not clear, but the infection is now known to involve multiple organs. Circulating immune complexes, overwhelming viremia, or an uncontrolled immune response may be contributing factors. In early hemorrhagic smallpox, death occurs suddenly about six days after the fever develops. Cause of death in hemorrhagic cases involved heart failure, sometimes accompanied by pulmonary edema. In late hemorrhagic cases, high and sustained viremia, severe platelet loss and poor immune response were often cited as causes of death. In flat smallpox modes of death are similar to those in burns, with loss of fluid, protein and electrolytes beyond the capacity of the body to replace or acquire, and fulminating sepsis.

Smallpox is caused by infection with variola virus, which belongs to the genus Orthopoxvirus, the family Poxviridae and subfamily chordopoxvirinae.

Cowpox originates on the udders or teats of cows. It is classified as a zoonotic disease, which means it can be transferred from animals to humans and vice versa. Cowpox is an infectious disease. So, the disease can manifest on cows in environments where bacteria thrive, due to unsanitary conditions, or randomly. Cowpox symptoms are similar in whichever host they infect: cow, cat, human. Cowpox symptoms include round, pus filled lesions on the skin at the site of infection. In most cases of humans, the lesions develop on the inner and outer parts of the hand and fingers. In some cases, the infected person can develop a mild fever or inflammation around the lesions. Cowpox can be transferred from human to human by contact of the infected site to another individual. It is very similar in pathology and structure in contrast to small pox. However, cowpox has increased activity in between the ectoderm and endoderm layers of the human skin. Cowpox includes both A type bodies and B type inclusion bodies which largely impacts the pathology of the disease.

Cowpox is an infectious disease caused by the cowpox virus. The virus, part of the orthopoxvirus family, is closely related to the "vaccinia" virus. The virus is zoonotic, meaning that it is transferable between species, such as from animal to human. The transferral of the disease was first observed in dairymaids who touched the udders of infected cows and consequently developed the signature pustules on their hands. Cowpox is more commonly found in animals other than bovines, such as rodents. Cowpox is similar to, but much milder than, the highly contagious and often deadly smallpox disease. Its close resemblance to the mild form of smallpox and the observation that dairymaids were immune from smallpox inspired the first smallpox vaccine, created and administered by English physician Edward Jenner.

The word “vaccination,” coined by Jenner in 1796, is derived from the Latin root "vaccinus", meaning of or from the cow. Once vaccinated, a patient develops antibodies that make them immune to cowpox, but they also develop immunity to the smallpox virus, or "Variola virus". The cowpox vaccinations and later incarnations proved so successful that in 1980, the World Health Organization announced that smallpox was the first disease to be eradicated by vaccination efforts worldwide. Other orthopox viruses remain prevalent in certain communities and continue to infect humans, such as the cowpox virus (CPXV) in Europe, vaccinia in Brazil, and monkeypox virus in Central and West Africa.

Paravaccinia virus originates from livestock infected with bovine papular stomatitis. When a human makes physical contact with the livestock's muzzle, udders, or an infected area, the area of contact will become infected. Livestock may not show symptoms of bovine papular stomatitis and still be infected and contagious. Paravaccinia can enter the body though all pathways including: skin contact by mechanical means, through the respiratory tract, or orally. Oral or respiratory contraction may be more likely to cause systemic symptoms such as lesions across the whole body

A person who has not previously been infected with paravaccinia virus should avoid contact with infected livestock to prevent contraction of disease. There is no commercially available vaccination for cattle or humans against paravaccinia. However, following infection, immunization has been noted in humans, making re-infection difficult. Unlike other pox viruses, there is no record of contracting paravaccinia virus from another human. Further, cattle only show a short immunization after initial infection, providing opportunity to continue to infect more livestock and new human hosts.

Alastrim, also known as variola minor, was the milder strain of the variola virus that caused smallpox. The last known case of variola minor was in Somalia, Africa in 1977. Smallpox was formally declared eradicated in May 1980.

Variola minor is of the genus orthopoxvirus, which are DNA viruses that replicate in the cytoplasm of the affected cell, rather than in its nucleus. Like variola major, alastrim was spread through inhalation of the virus in the air, which could occur through face-to-face contact or through fomites. Infection with variola minor conferred immunity against the more dangerous variola major.

Variola minor was a less common form of the virus, and much less deadly. Although alastrim had the same incubation period and pathogenetic stages as smallpox, alastrim is believed to have had a mortality rate of less than 1%, as compared to smallpox's 30%.

Because alastrim was a less debilitating disease than smallpox, patients were more frequently ambulant and thus able to infect others more rapidly. As such, variola minor swept through the USA, Great Britain, and South Africa in the early 20th century, becoming the dominant form of the disease in those areas and thus rapidly decreasing mortality rates.

Alastrim was also called white pox, kaffir pox, Cuban itch, West Indian pox, milk pox, and pseudovariola.

Like smallpox, alastrim has now been totally eradicated from the globe thanks to the 1960s Global Smallpox Eradication campaign. The last case of indigenous variola minor was reported in a Somalian cook, Ali Maow Maalin, in October 1977, and smallpox was officially declared eradicated worldwide in May 1980.

The duration of the visible blistering caused by varicella zoster virus varies in children usually from 4 to 7 days, and the appearance of new blisters begins to subside after the fifth day. Chickenpox infection is milder in young children, and symptomatic treatment, with sodium bicarbonate baths or antihistamine medication may ease itching. It is recommended to keep new infants from birth up to age 6 months away from an infected person for 10 to 21 days because their immune systems are not developed enough to handle the stress it can bring on. Paracetamol (acetaminophen) is widely used to reduce fever. Aspirin, or products containing aspirin, should not be given to children with chickenpox, as it can cause Reye's Syndrome.

In adults, the disease is more severe, though the incidence is much less common. Infection in adults is associated with greater morbidity and mortality due to pneumonia (either direct viral pneumonia or secondary bacterial pneumonia), bronchitis (either viral bronchitis or secondary bacterial bronchitis), hepatitis, and encephalitis. In particular, up to 10% of pregnant women with chickenpox develop pneumonia, the severity of which increases with onset later in gestation. In England and Wales, 75% of deaths due to chickenpox are in adults. Inflammation of the brain, or encephalitis, can occur in immunocompromised individuals, although the risk is higher with herpes zoster. Necrotizing fasciitis is also a rare complication.

Varicella can be lethal to adults with impaired immunity. The number of people in this high-risk group has increased, due to the HIV epidemic and the increased use of immunosuppressive therapies. Varicella is a particular problem in hospitals, when there are patients with immune systems weakened by drugs (e.g., high-dose steroids) or HIV.

Secondary bacterial infection of skin lesions, manifesting as impetigo, cellulitis, and erysipelas, is the most common complication in healthy children. Disseminated primary varicella infection usually seen in the immunocompromised may have high morbidity. Ninety percent of cases of varicella pneumonia occur in the adult population. Rarer complications of disseminated chickenpox include myocarditis, hepatitis, and glomerulonephritis.

Hemorrhagic complications are more common in the immunocompromised or immunosuppressed populations, although healthy children and adults have been affected. Five major clinical syndromes have been described: febrile purpura, malignant chickenpox with purpura, postinfectious purpura, purpura fulminans, and anaphylactoid purpura. These syndromes have variable courses, with febrile purpura being the most benign of the syndromes and having an uncomplicated outcome. In contrast, malignant chickenpox with purpura is a grave clinical condition that has a mortality rate of greater than 70%. The cause of these hemorrhagic chickenpox syndromes is not known.

Variola caprina (goat pox) is a contagious viral disease caused by a pox virus that affects goats. The virus usually spreads via the respiratory system, and sometimes spreads through abraded skin. It is most likely to occur in crowded stock. Sources of the virus include cutaneous lesions, saliva, nasal secretions and faeces. There are two types of the disease: the papulo-vesicular form and the nodular form (stone pox). The incubation period is usually 8–13 days, but it may be as short as four days.

It is thought the same virus spreads sheep pox, to which European sheep breeds are highly susceptible. The virus may be present in dried scabs for up to six months.

In endemic areas the morbidity rate is 70–90% and the mortality rate is 5–10%. The mortality rate may reach nearly 100% in imported animals. Resistant animals may show only a mild form of the disease, which may be missed as only a few lesions are present, usually around the ears or the tail.

Paravaccinia is a member of the Parapoxvirus family. It has a cylindrical body about 140 X 310 nm in size, with convex ends covered in a criss-cross pattern of rope like structures. The virus is resistant to cold, dehydration, and temperatures up to 56 °C. Upon injecting a cell with its genome, the virus begins transcription in the cytoplasm using viral RNA polymerase. As the virus progresses through the cell, the host begins to replicate the viral genome between 140 minutes and 48 hours.

After a chickenpox infection, the virus remains dormant in the body's nerve tissues. The immune system keeps the virus at bay, but later in life, usually in an adult, it can be reactivated and cause a different form of the viral infection called shingles (also known as herpes zoster).

The United States Advisory Committee on Immunization Practices (ACIP) suggests that every adult over the age of 60 years get the "herpes zoster" vaccine.

Shingles affects one in five adults infected with chickenpox as children, especially those who are immune-suppressed, particularly from cancer, HIV, or other conditions. Stress can bring on shingles as well, although scientists are still researching the connection. Shingles are most commonly found in adults over the age of 60 who were diagnosed with chickenpox when they were under the age of 1.

Goat pox is found in the part of Africa north of the equator, the Middle East, Central Asia and India. It may be spread between animals by:

- Direct contact

- Indirect transmission by contaminated implements, vehicles or products such as litter or fodder

- Indirect transmission by insects (mechanical vectors).

- Contamination by inhalation, intradermal or subcutaneous inoculation, or by respiratory, transcutaneous and transmucosal routes

Pigeon pox is a viral disease to which pigeons are susceptible. There is a live viral vaccine available (ATCvet code: ). Pigeon pox is caused by a virus that is spread by mosquitoes and dirty water but not in droppings.

The U.S. Centers for Disease Control and Prevention (CDC) publishes a journal "Emerging Infectious Diseases" that identifies the following factors contributing to disease emergence:

- Microbial adaption; e.g. genetic drift and genetic shift in Influenza A

- Changing human susceptibility; e.g. mass immunocompromisation with HIV/AIDS

- Climate and weather; e.g. diseases with zoonotic vectors such as West Nile Disease (transmitted by mosquitoes) are moving further from the tropics as the climate warms

- Change in human demographics and trade; e.g. rapid travel enabled SARS to rapidly propagate around the globe

- Economic development; e.g. use of antibiotics to increase meat yield of farmed cows leads to antibiotic resistance

- Breakdown of public health; e.g. the current situation in Zimbabwe

- Poverty and social inequality; e.g. tuberculosis is primarily a problem in low-income areas

- War and famine

- Bioterrorism; e.g. 2001 Anthrax attacks

- Dam and irrigation system construction; e.g. malaria and other mosquito borne diseases

Key measures to prevent outbreaks of the disease are maintaining hygiene standards and using screening to exclude persons with suspicious infections from engaging in contact sports. A skin check performed before practice or competition takes place can identify individuals who should be evaluated, and if necessary treated by a healthcare professional. In certain situations, i.e. participating in wrestling camps, consider placing participants on valacyclovir 1GM daily for the duration of camp. 10-year study has shown 89.5% reduction in outbreaks and probable prevention of contracting the virus. Medication must be started 5 days before participation to ensure proper concentrations exist.

Herpes gladiatorum is only caused by the herpes simplex virus. Shingles, also manifesting as skin rashes with blisters, is caused by a different virus, herpes zoster. Other agents may cause skin infections, for example ringworm is primarily due to the fungal dermatophyte, "T. tonsurans". Impetigo, cellulitis, folliculitis and carbuncles are usually due to "Staphylococcus aureus" or Beta-hemolytic streptococcus bacteria. These less common forms can be potentially more serious. Anti-viral treatments will not have an effect in non-viral cases. Bacterial infections must be treated with antibiotics and fungal infections with anti-fungal medication.

Hemorrhagic smallpox, sometimes called bloody pox, fulminant smallpox, and blackpox, is a severe and rare form of smallpox and is usually fatal. Like all forms of smallpox it is caused by the variola virus. It is characterized by an incubation period of 7 to 14 days. It has two stages, the first begins with fever, headache, chills, nausea, vomiting and severe muscle aches. The skin flushes in a deep-purple, uneven pattern across the face. The early stage is often mistaken for measles. The late stage is characterized by the appearance of small blisters resembling a severe form of chickenpox. These small blisters then flatten until they are even with the skin, and change into reddish lesions similar to those seen in measles. The skin then turns a deep purple. Lesions appear inside the mouth and active bleeding from oral and nasal mucous membranes is common. This is followed by active bleeding in the gastrointestinal tract, and blood appears in the stool and urine. Blood studies resemble the clinical values of disseminated intravascular coagulation.

Eczema vaccinatum is a serious medical condition that requires immediate and intensive medical care. Therapy has been supportive, such as antibiotics, fluid replacement, antipyretics and analgesics, skin healing, etc.; vaccinia immune globulin (VIG) could be very useful but supplies may be deficient as of 2006. Antiviral drugs have been examined for activity in pox viruses and cidofovir is believed to display potential in this area.

In March 2007, a two-year-old Indiana boy and his mother contracted the life-threatening vaccinia infection from his father who was vaccinated against smallpox as part of the standard vaccination protocol for individuals serving in the US armed forces beginning in 2002. The child developed the pathognomonic rash which typifies eczema vaccinatum over 80 percent of his body surface area. The boy has a history of eczema, which is a known risk factor for vaccinia infection.

An emerging infectious disease (EID) is an infectious disease whose incidence has increased in the past 20 years and could increase in the near future. Emerging infections account for at least 12% of all human pathogens. EIDs are caused by newly identified species or strains (e.g. Severe acute respiratory syndrome, HIV/AIDS) that may have evolved from a known infection (e.g. influenza) or spread to a new population (e.g. West Nile fever) or to an area undergoing ecologic transformation (e.g. Lyme disease), or be "reemerging" infections, like drug resistant tuberculosis. Nosocomial (hospital-acquired) infections, such as methicillin-resistant Staphylococcus aureus are emerging in hospitals, and extremely problematic in that they are resistant to many antibiotics. Of growing concern are adverse synergistic interactions between emerging diseases and other infectious and non-infectious conditions leading to the development of novel syndemics. Many emerging diseases are zoonotic - an animal reservoir incubates the organism, with only occasional transmission into human populations.

Only 8% of infected horses have this form of pigeon fever, however, it has a 30-40% fatality rate. Organs that are commonly affected are the liver, spleen, and lungs. For a successful recovery, long-term antimicrobial therapy is essential.

Farmyard pox is a group of closely related parapoxviruses of sheep and cattle that cause similar diseases in humans. Conditions included in this group are:

The disease can occur in horses of any age, breed or gender. In the US, it occurs throughout the country and at any time of year. The disease was traditionally thought to occur mainly in dry, arid regions, but from at least 2005, its range has been increasing into areas where it was not previously seen, such as the Midwestern US, and Western Canada. Environmental risk factors include over 7 days of a weekly average land surface temperatures above 35 °C, and drier soils; these factors were implicated in an outbreak in Kansas in 2012.

, there is no vaccine effective for prevention. Several vaccines based on treponemal proteins reduce lesion development in an animal model, and research is ongoing.