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Smallpox

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Last Updated: 02 July 2021

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General | Latest Info

Smallpox

Other namesVariola, variola vera, pox, red plague
SpecialtyInfectious disease
ComplicationsScarring of the skin, blindness
Usual onset1 to 3 weeks following exposure
DurationAbout 4 weeks
CausesVariola major , Variola minor (spread between people)
Diagnostic methodBased on symptoms and confirmed by PCR
Differential diagnosisChickenpox , impetigo , molluscum contagiosum , monkeypox
PreventionSmallpox vaccine
TreatmentSupportive care
Prognosis30% risk of death
FrequencyEradicated (last wild case in 1977)
Pustular eruption of smallpox on face Wellcome L0032957.jpg "Pustular eruption of smallpox on face Wellcome L0032957.jpg", by https://wellcomeimages.org/indexplus/obf_images/dc/ea/be5f8d447d5ad4063106c89c4232.jpg, licensed under CC BY 4.0

Smallpox is an extremely contagious and deadly virus for which there is no known cure. The last known case occurred in the United States in 1949 and due to worldwide Vaccination programs, this disease has been completely eradicate. Smallpox is also known as Variola. Since the time of ancient Egypt, Smallpox has proven to be one of the most devastating diseases to humankind. Widespread Smallpox epidemics and huge death tolls fill pages of our history books. The first Smallpox Vaccine was created in 1758. However, disease will continue to infect and kill people on a widespread basis for another 200 years. The World Health Organization implemented strict vaccination standards in order to slow the infection rate. The last known natural case occurred in 1977 in Somalia. By 1980, WHO declared that Smallpox had been completely eradicate, although government and health agencies still have stashes of Smallpox Virus for research purposes. People no longer receive routine Smallpox vaccinations. Smallpox Vaccine can have potentially fatal side effects, so only people WHO are at high risk of exposure get Vaccine.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

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Classification

Case fatality rate (CFR) and frequency of smallpox by type and vaccination status according to Rao case study

Type of diseaseOrdinary ConfluentOrdinary SemiconfluentOrdinary DiscreteModifiedFlatEarly HemorrhagicLate hemorrhagic
Vaccinated CFR26.3%8.4%0.7%0%66.7%100%89.8%
Unvaccinated CFR62%37%9.3%0%96.5%100%96.8%
Vaccinated Frequency4.6%7%58.4%25.3%1.3%1.4%2.0%
Unvaccinated Frequency22.8%23.9%42.1%2.1%6.7%0.7%1.7%

Thousands of years ago, Variola virus emerged and began causing illness and deaths in human populations, with smallpox outbreaks occurring from time to time. Thanks to success of vaccination, last natural outbreak of smallpox in the United States occurred in 1949. In 1980, World Health Assembly declared smallpox eradicate, and no cases of naturally occurring smallpox have happened since. Smallpox research in the United States continues and focuses on development of vaccines, drugs, and diagnostic tests to protect people against smallpox in the event that it is used as an agent of bioterrorism.

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Signs and symptoms

The first symptoms of smallpox usually appear 10 to 14 days after you're infect. During the incubation period of seven to 17 days, you look and feel healthy and can't infect others. Following the incubation period, sudden onset of flu-like signs and symptoms occurs. These include: fever Overall discomfort Headache Severe Fatigue Severe back pain Vomiting, possibly a few days later, flat, red spots appear first on your face, hands and forearms, and later on your trunk. Within a day or two, many of these lesions turn into small blisters filled with clear fluid, which then turn into pus. Scabs begin to form eight to nine days later and eventually fall off, leaving deep, pitted scars. Lesions also develop in mucous membranes of your nose and mouth and quickly turn into sores that break open.

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Cause

Smallpox is caused by infection with the Variola virus. Disease is spread through person-to-person contact, most often from inhalation of droplet nuclei expel through the back of the throat of an infected person. Droplet nuclei are small particles containing virus-infected respiratory secretions that are pushed out into the air by coughing or sneezing. These airborne particles may then be inhaled by another person. Individuals with smallpox are most infectious during the first week of illness. Smallpox may also be spread through direct contact with an infected person or through contact with contaminated material such as clothing, blankets or bed linen.


What are the symptoms of smallpox?

The Variola virus causes smallpox. In the past, people spread smallpox most commonly through direct, prolonged face-to-face contact with others. When they sneeze or cough, they would send respiratory particles through the air. When other people inhale these large droplets, they would become infected. Less commonly, people become infected by direct contact with rash or crust material from swab. People also spread viruses to each other by sharing sheets, towels and clothing. The disease is most contagious when sores first appear in the throat and mouth. But people with smallpox are contagious for several weeks after the first sores develop.

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Diagnosis

Table

ConditionAgentDistinguishing Features
ChickenpoxVZVSee Distinguishing Features Between Smallpox, Monkeypox, and Chickenpox below
Human monkeypoxMonkeypox virusSee Monkeypox below
Naturally occurring vaccinia virus infection bNaturally occurring vaccinia virusLesions tend to occur on the hands and forearms Cases generally have exposure to infected cattle (usually dairy cows) Occurs in certain areas of the world with endemic disease in cattle (such as Brazil)
Disseminated herpes zosterVZVUsually occurs in immunocompromised hosts History of chickenpox
ImpetigoStaphylococcus aureus Streptococcus pyogenesLesions often pruritic and not painful Lesions focal and not usually disseminated Lesions not "shotty" Gold-colored crusted plaques are classic Lesions superficial and not embedded into dermis Constitutional symptoms generally absent or minimal Usually occurs in children
Hand, foot, and mouth diseaseCoxsackievirusUsually occurs in children <10 yr of age Has autumn seasonal pattern Lesions may be confined to hands and feet (although dissemination may occur)
Disseminated herpes simplexHerpes simplex virusUsually occurs in immunocompromised hosts Lesions are vesicular and do not progress to pustules
Secondary syphilisTreponema pallidumRash generally does not include vesicular phase Lesions not "shotty" Constitutional symptoms relatively mild Lesions generally evolve slowly from macules to papules to pustules (often over several weeks)
Molluscum contagiosumMolluscipoxvirusUsually occurs in healthy children or HIV-positive adults In healthy adults, lesions generally occur in genital area Lesions are painless Constitutional symptoms generally are absent Lesions may persist for several months (or longer in immunocompromised patients)
Erythema multiforme major (including Stevens-Johnson syndrome)Associated with various infectious and noninfectious processesConstitutional symptoms and rash usually appear at same time Rash evolves rapidly Bullae or "bull's-eye" lesions common Extensive mucous membrane involvement, including conjunctivitis, common
Drug eruptionsNoninfectiousLesions generally not pustular History of drug exposure Fever may be present, but severe toxemia usually absent
Bullous pemphigoidNoninfectiousTense bullae characteristic Occurs most commonly in elderly Intense pruritus may be present Constitutional symptoms usually absent Peripheral eosinophilia may be noted
Other skin conditionsNoninfectiousAcne Insect bites Contact dermatitis
MeningococcemiaNeisseria meningitidisRapid progression to shock and often death
Hemorrhagic varicellaVZVUsually occurs in immunocompromised children
Rocky Mountain spotted feverRickettsia rickettsiiTick exposure history may be obtained Occurs April through May Most US cases occur in southeastern and south-central states
EhrlichiosisEhrlichia chaffeensis Erhlichia phagocytophiliaTick exposure history may be obtained Petechial rash uncommon Peripheral blood smear may show morulae in neutrophils of patients with human granulocytic ehrlichiosis
Septicemia caused by gram-negative bacteriaVarious bacterial agentsUnderlying illness usually present

Other poxviruses can mimic the way Smallpox looks but are significantly less lethal than Smallpox. Some of these are closely related to the Variola virus. There are several zoonotic versions of orthopoxvirus, family of virus that includes Variola, which is cause of Smallpox. These often look like Smallpox and can be similar. Some can be serious. Cowpox affects both cows and humans. Before clinical vaccination was widespread, farmers would develop some inoculation of Variola through exposure to cowpox. Vaccinia is another virus that affects cattle and is the base virus for the Smallpox vaccine. Monkeypox is most closely related to Smallpox and still naturally infects humans in some African nations. It has a mortality rate of 1 to 10 percent. Camelpox affects camels and can cross over to humans. Buffalopox is closely related to vaccinia and is common in India. Chickenpox is primarily child illness from varicella-zoster virus. Kids don't usually have fever or other signs and symptoms before pox lesions appear. As mentioned above, chickenpox lesions are less robust than those of Smallpox and are very unlikely to appear on palms or soles of feet. Shingles is a secondary infection from the same varicella virus and appears mostly in older adults. Shingles lesions follow major nerve pathways and are nearly always on one side of the body.


Smallpox

Smallpox, like other poxviruses, has lesions that can cover the entire body. Physicians will not likely begin to diagnose smallpox until lesions become obvious. At that point, healthcare providers will attempt to gain a history of illness prior to the appearance of lesions. To determine the difference between smallpox and chickenpox, healthcare providers will be looking at the formation of lesions as the most important sign. Smallpox: Lesions are hard and well-define. All lesions will develop at the same rate and will be similar in their formation and firmness. Sometimes, lesions will have small indentation on their crown, know as umbilical formation. Smallpox Lesions are often preceded up to one to four days by fever as high as 105 degrees. Lesions will be distributed on arms and face and appear on palms and soles of feet. Chickenpox: Lesions are not as well-define and will be at different stages of development. They are not firm and will be easy to remove. There will not likely be any fever preceding the onset of Lesions. Lesions are likely to appear first on the torso rather than on the arms and face. They will rarely appear on palms or soles of feet. If you or someone in your family develop lesions that appear to be chickenpox or smallpox, see healthcare provider.

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Risk and Clinical and Public Health Response

Risk CategoryRisk CriteriaClinical and Public Health Response
High riskMeets all three major smallpox criteriaObtain urgent Infectious Disease and/or Dermatology consultation. If after consultation patient is still considered to have a high risk for smallpox: Classify as a probable smallpox case and treat as a medical and public health emergency. Contact CDCs Emergency Operations Center at 770-488-7100 for assistance, including specimen collection and testing. Take digital photos for consultation with experts. Treat patient as clinically indicated. Do not delay treatment for other likely conditions in the differential diagnosis while awaiting response team. Do not proceed with laboratory testing for other diagnoses until smallpox has been ruled out.
Moderate riskFebrile prodrome AND 1 other major smallpox criterion OR Febrile prodrome AND 4 minor smallpox criteriaObtain urgent Infectious Disease and/or Dermatology consultation. If after consultation patient is still considered to have a moderate risk for smallpox: Perform laboratory testing for confirmation or exclusion of varicella or other diagnoses in the differential diagnosis. Initiate treatment for likely etiology as clinically indicated.
Low riskNo febrile prodrome OR febrile prodrome AND < 4 minor smallpox criteriaIf diagnosis is uncertain, test for varicella. Manage as clinically indicated.

Common Conditions That Might Be Confused with Smallpox

ConditionClinical Clues
Varicella (primary infection with varicella-zoster virus)Most common in children <10 years Children usually do not have a viral prodrome
Disseminated herpes zosterImmunocompromised or elderly persons Rash looks like varicella, usually begins in dermatomal distribution
Impetigo ( Streptococcus pyogenes, Staphylococcus aureus)Honey-colored crusted plaques with bullae are classic but may begin as vesicles Regional, not disseminated rash Patients generally not ill
Drug eruptionsExposure to medications Rash often generalized
Contact dermatitisItching Contact with possible allergens Rash often localized in a pattern suggesting external contact
Erythema multiforme minorTarget, bulls eye, or iris lesion Often follows recurrent herpes simplex virus infections May involve hands and feet (including palms and soles)
Erythema multiforme major (Stevens-Johnson syndrome)Major form involves mucous membranes and conjunctivae There may be target lesions or vesicles
Enteroviruses infection, especially Hand, Foot, and Mouth DiseaseSummer and fall Fever and mild pharyngitis 1 to 2 days before rash onset Lesions initially maculopapular but evolve into whitish-grey, tender, flat, and often oval vesicles Peripheral distribution (hands, feet, mouth, or disseminated)
Disseminated herpes simplexLesions indistinguishable from varicella Immunocompromised host
Scabies; insect bite (including fleas)Itching is a major symptom Patient is not febrile and is otherwise well
Molluscum contagiosumMay disseminate in immunosuppressed persons Can occur anywhere on the body Presents as small, raised, and usually white, pink, or flesh-colored lesions with a dimple or pit in the center
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Prevention

The Variola major has a 10-to 12-day incubation period, followed by 2-to 3-day prodrome of fever, headache, backache, and extreme malaise. Sometimes severe abdominal pain and vomiting occur. After prodrome, maculopapular lesions develop on oropharyngeal mucosa, face, and arms, spreading shortly thereafter to trunk and legs. Oropharyngeal lesions quickly ulcerate. After 1 or 2 days, cutaneous lesions become vesicular, then pustular. Pustules are denser on the face and extremities than on trunk, and they may appear on palms. The pustules are round and tense and appear deeply embed. Skin lesions of smallpox, unlike those of chickenpox, are all at the same stage of development on give body part. After 8 or 9 days, pustules become crusted. Severe residual scarring is typical. Diagnosis of smallpox is confirmed by documenting the presence of variola DNA by PCR of vesicular or pustular samples. Or virus can be identified by electron microscopy or viral culture of material scrapped from skin lesions and subsequently confirmed by PCR. Suspect smallpox must be reported immediately to local public health agencies or CDC at 770-488-7100. These agencies then arrange for testing in laboratory with high-level containment capability. Treatment of smallpox is generally supportive, with antibiotics for secondary bacterial infections. However, antiviral drug tecovirimat was approved by the US Food and Drug Administration in 2018 based on experimental studies and is the first drug to be licensed for treatment of smallpox. Although its effectiveness against smallpox in humans is unknown, tecorvirimat would likely be the drug of choice for attempted treatment and is available in the US Department of Health and Human Services Strategic National Stockpile. Cidofovir and investigational drug brincidofovir also be consider. License smallpox vaccines in the US consist of live replication-competent vaccinia virus and JYNNEOS, live attenuate modified vaccinia Ankara vaccine. Vaccinia is related to smallpox and provides cross-immunity. ACAM2000 vaccine is administered with bifurcated needle dip in reconstituted vaccine. The needle is rapidly jabbed 15 times in an area about 5 mm in diameter and with sufficient force to draw traces of blood. Vaccine sites are covered with dressing to prevent spread of the vaccine virus to other body sites or to close contacts. Fever, malaise, and myalgias are common week after vaccination. Successful vaccination is indicated by development of pustule by about 7 day. Revaccination may cause only papule surrounded by erythema, which peaks between 3 and 7 days. People without such signs of successful vaccination should be given another dose of vaccine. Some serious vaccine complications are treated with vaccinia immune globulin; one case of eczema vaccinatum apparently treated successfully with VIG, cidofovir, and tecovirimat has been report. In the past, high-risk patients who required vaccination because of viral exposure were simultaneously given VIG to try to prevent complications. The efficacy of this practice is unknown, and it is not recommended by CDC. VIG is available only from the CDC.


Smallpox Vaccine

The Smallpox vaccination procedure is different from other common vaccination procedures, such as shot. The Procedure starts by dipping a bifurcate needle into the vaccine solution and then pricking upper arm skin several times in a few seconds with that needle. Although pricking is superficial, it may develop sores on the skin. After successful vaccination, red and itchy blister develop at the vaccination site within 3 to 4 days, which eventually turns into large blister filled with pus. During 2 weeks of vaccination, blister begins to dry, forming scab, which fall off in 3 week.Sss

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Treatment

Smallpox vaccination within three days of exposure will prevent or significantly lessen the severity of smallpox symptoms in the vast majority of people. Vaccination four to seven days after exposure can offer some protection from disease or may modify the severity of the disease. Other than vaccination, treatment of smallpox is primarily supportive, such as wound care and infection control, fluid therapy, and possible ventilator assistance. Flat and hemorrhagic types of smallpox are treated with the same therapies used to treat shock, such as fluid resuscitation. People with semi-confluent and confluent types of smallpox may have therapeutic issues similar to patients with extensive skin burns. In July 2018, Food and Drug Administration approved tecovirimat, first drug approved for treatment of smallpox. Antiviral treatments have improved since the last large smallpox epidemic and studies suggest that the antiviral drug cidofovir might be useful as a therapeutic agent. Drugs must be administered intravenously, and may cause serious kidney toxicity. ACAM2000 is a smallpox vaccine developed by Acambis. It was approved for use in the United States by the US FDA on August 31 2007. It contains live vaccinia virus, clone of the same strain used in earlier vaccine, Dryvax. While Dryvax virus was cultured in the skin of calves and freeze-dry, ACAM2000s virus is cultured in kidney epithelial cells from African green monkey. Efficacy and adverse reaction incidence are similar to Dryvax. Vaccine is not routinely available to the US public; it is, however, used in the military and maintained in the Strategic National Stockpile.


Antiviral Drugs

In July 2018, FDA approved tecovirimat for the treatment of smallpox. In laboratory tests, tecovirimat has been shown to stop growth of the virus that causes smallpox and to be effective in treating animals that had diseases similar to smallpox. Tecovirimat has not been tested in people who are sick with smallpox, but it has been given to healthy people. Test results in healthy people show that it is safe and causes only minor side effects. In addition to treating smallpox disease, tecovirimat could also be used under investigational new Drug protocol to treat adverse reactions from vaccinia vaccination. In laboratory tests, cidofovir and brincidofovir have also been shown to stop growth of the virus that caused smallpox and to be effective in treating animals that had diseases similar to smallpox. Cidofovir and brincidofovir have not been tested in people who are sick with smallpox, but they have been tested in healthy people and in those with other viral illnesses. These Drugs continue to be evaluated for effectiveness and toxicity. Neither are FDA-approve for treatment of variola virus infections, but they could be used for isolated cases or during outbreaks under appropriate regulatory mechanism for treatment of complications from vaccinia vaccination. Because these drugs were not tested in people sick with smallpox, it is not know if people with smallpox would benefit from treatment with them. However, their use may be considered if there is ever smallpox outbreak. Tecovirimat and cidofovir are currently Stockpile by the Assistant Secretary for Preparedness and Response strategic National Stockpile external icon, which has medicine and medical supplies to protect the American public if there is a public health emergency, including one involving smallpox.

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Prognosis

The mortality rate from Variola minor is approximately 1 %, while the mortality rate from Variola major is approximately 30 %. Ordinary type-confluent is fatal about 50-75 percent of time, ordinary-type semi-confluent about 25-50 percent of time, in cases where rash is discrete 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 or late hemorrhagic type smallpox is 90 percent or greater and nearly 100 percent is observed in cases of early 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 cases of flat smallpox in vaccinated people, condition was extremely rare but less lethal, with one case series showing 66. 7 % death rate. In fatal cases of ordinary smallpox, death usually occurs between tenth and sixteenth days of illness. The cause of death from smallpox is not clear, but infection is now known to involve multiple organs. Circulating immune complexes, overwhelming viremia, or uncontrolled immune response may be contributing factors. In early hemorrhagic smallpox, death occurs suddenly about six days after fever develops. The cause of death in early hemorrhagic cases is commonly due to heart failure and pulmonary edema. In late hemorrhagic cases, high and sustained viremia, severe platelet loss and poor immune response are 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, and fulminating sepsis.

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History

The history of Smallpox holds a unique place in medicine. One of the deadliest diseases known to humans, it is also the only human disease to have been eradicated by vaccination. Symptoms of typical Smallpox infection begin with fever and lethargy about two weeks after exposure to the Variola virus. Headache, sore throat, and vomiting were common as well. In a few days, raise rashes appear on the face and body, and sores form inside the mouth, throat, and nose. Fluid-fill pustules would develop and expand, in some cases joining together and covering large areas of skin. In about third week of illness, scabs form and separate from the skin. About 30 % of cases end in death, typically in the second week of infection. Most survivors had some degree of permanent scarring, which could be extensive. Other deformities could result, such as loss of lip, nose, and ear tissue. Blindness could occur as a result of corneal scarring. Smallpox was spread by close contact with sores or respiratory droplets of an infected person. Contaminate bedding or clothing could also spread the disease. The patient remains infectious until the last scab is separated from skin. Smallpox plagued human populations for thousands of years. Researchers who examined the mummy of Egyptian pharaoh Ramses V observe scarring similar to that from Smallpox on his remains. Ancient Sanskrit medical texts, dating from about 1500 BCE, describe Smallpox-like illness. Smallpox was likely present in Europe by about 300 CE. Some estimates indicate that 20-century worldwide deaths from Smallpox number more than 300 million. The last known case of wild Smallpox occurred in Somalia in 1977. Bibliography for Smallpox Timeline

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Society and culture

In the face of the devastation of Smallpox, various Smallpox gods and goddesses have been worshipped throughout parts of the Old World, for example in China and in India. In China, Smallpox goddess was referred to as t'ou-Shen Niang-Niang. Chinese believers actively work to appease the goddess and pray for her mercy, by such measures as referring to Smallpox pustules as beautiful flowers as a euphemism intended to avert offending goddess, for example. In a related New Year's Eve custom, it was prescribed that children house wear ugly masks while sleeping, so as to conceal any beauty and thereby avoid attracting goddess, WHO would be passing through sometime that night. If case of Smallpox do occur, shrines would be set up in homes of victims, to be worship and offer to as disease run its course. If the victim recover, shrines are removed and carried away in special paper chair or boat for burning. If the patient does not recover, shrine was destroyed and curse, so as to expel the goddess from the house. In the Yoruba language, Smallpox is known as Sopona, but it is also written as shakpanna, Shopona, shapana, and sopono. The word is a combination of 3 words, verb san, meaning to cover or plaster, kpa or pa, meaning to kill, and enia, meaning human. Roughly translate, it means one WHO kills person by covering them with pustules. Among Yoruba people of West Africa, and also in the Dahomean religion, Trinidad, and in Brazil, deity Sopona, also know as Obaluaye, is deity of Smallpox and other deadly diseases. One of the most feared deities of the orisha pantheon, Smallpox was seen as a form of punishment from Shopona. The worship of Shopona was highly controlled by his priests, and it was believed that priests could also spread Smallpox when anger. However, Shopona was also seen as a healer WHO could cure diseases he inflict, and he was often called upon by his victims to heal them. The British government banned worship of god because it was believed his priests were purposely spreading Smallpox to their opponents. India's first records of Smallpox can be found in medical books that date back to 400 CE. This book describes a disease that sounds exceptionally like Smallpox. India, like China and Yoruba, created goddess in response to its exposure to Smallpox. The Hindu goddess Shitala was both worshipped and feared during her reign. It was believed that this goddess was both evil and kind and had the ability to inflict victims when anger, as well as calm fevers of already afflict. Portraits of goddess show her holding the broom in her right hand to continue to move the disease and a pot of cool water in the other hand in an attempt to soothe victims.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

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Overview

There have n't been any confirmed cases of smallpox since it was wiped out. Before that, smallpox was a life-threatening disease. Millions of people get smallpox every year. Up to 30 % of people die of their illness. The death was due to systemic shock and toximemia. Smallpox is a very contagious disease, with secondary attacks affecting up to 80 % of house hold contacts. Often, people WHO survive disease have long-term problems, such as blindness and severe scarring. Researchers believe that the disease first appeared in the third century. For thousands of years, smallpox spread throughout the world. In the 1960s, WHO led worldwide effort to eliminate smallpox.


Smallpox Symptoms

When you're first exposed to the smallpox virus, you're in what's called the incubation period. You aren't contagious and you won't have symptoms for another 7 to 19 days. Symptoms of smallpox start with high fever, headache, fatigue, body aches, and sometimes vomiting, all of which can last from two to four days. You may be contagious at this point. A few days later, you will develop flat rash that starts in your mouth and spreads, turning into raise bumps and pus-fill blisters that crust, scab, and fall off after about three weeks, leaving a pitted scar. You may also develop blisters in your nose and mouth.

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Cleaning and Disinfection of Environmental Surfaces

Table

DisinfectantMinimum Concentration to Achieve Inactivation
Ethyl alcohol40%
Isopropyl alcohol40%
Benzalkonium chloride100 ppm
Sodium hypochlorite200 ppm
Ortho -phenylphenol40%
Iodophor75 ppm

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

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Sources

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

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