How can smallpox be prevented. What vaccines are available for smallpox prevention. Are antiviral drugs effective against smallpox. What supportive care measures are used for smallpox patients. How does vaccination timing affect smallpox protection.

Smallpox Vaccines: A Shield Against the Eradicated Virus

Smallpox, a once-dreaded disease, has been eradicated globally. However, the threat of its potential re-emergence keeps the medical community vigilant. Vaccines remain the primary defense against smallpox, should it ever resurface.

Two licensed smallpox vaccines are currently available in the United States:

• ACAM2000
• APSV (Aventis Pasteur Smallpox Vaccine)

These vaccines are classified as replication-competent, meaning they contain live vaccinia virus, a less harmful relative of the smallpox virus. Additionally, an investigational vaccine is held in reserve for potential emergencies.

How do smallpox vaccines work?

Smallpox vaccines stimulate the immune system to produce antibodies against the vaccinia virus. Due to the similarity between vaccinia and smallpox viruses, these antibodies also provide protection against smallpox. The vaccine’s effectiveness depends on the timing of administration relative to exposure:

• Pre-exposure: Offers the highest level of protection, potentially preventing infection entirely.
• Within 3 days of exposure: May prevent disease or significantly reduce its severity.
• 4-7 days post-exposure: Provides some protection and may lessen the severity of symptoms.
• After rash onset: Vaccination is no longer effective in preventing or modifying the disease course.

Antiviral Drugs: Expanding the Arsenal Against Smallpox

While vaccines remain the cornerstone of smallpox prevention, antiviral drugs have emerged as potential treatments for infected individuals. Three antiviral medications have shown promise in laboratory studies and animal models:

1. Tecovirimat (TPOXX)

FDA-approved in July 2018, tecovirimat is the first antiviral drug specifically indicated for smallpox treatment. How does tecovirimat work against smallpox?

Tecovirimat inhibits a protein essential for the smallpox virus to spread from cell to cell, effectively halting its replication. While it has not been tested in individuals with active smallpox infections, studies in healthy volunteers have demonstrated its safety and tolerability.

2. Brincidofovir (TEMBEXA)

Brincidofovir received FDA approval for smallpox treatment in June 2021. This antiviral drug has shown efficacy in laboratory studies and animal models of smallpox-like diseases. How does brincidofovir differ from tecovirimat?

Unlike tecovirimat, which targets a specific viral protein, brincidofovir works by inhibiting viral DNA replication. It has been studied in humans for other viral infections, providing valuable safety data. Common side effects include gastrointestinal symptoms such as diarrhea, nausea, and abdominal pain.

3. Cidofovir

Although not FDA-approved for smallpox treatment, cidofovir has demonstrated potential in laboratory and animal studies. It remains under evaluation for effectiveness and toxicity. In an emergency, cidofovir could be used under appropriate regulatory mechanisms, such as an investigational new drug (IND) protocol or Emergency Use Authorization.

The Strategic National Stockpile: Preparing for the Unthinkable

The United States maintains a Strategic National Stockpile (SNS) to ensure readiness in the event of a public health emergency, including a potential smallpox outbreak. What does the SNS contain for smallpox preparedness?

• Smallpox vaccines: Sufficient quantities to vaccinate every person in the United States
• Tecovirimat: Stockpiled as a potential treatment option
• Cidofovir: Available for use under appropriate regulatory mechanisms

It’s important to note that brincidofovir is not currently included in the Strategic National Stockpile. The composition of the stockpile is regularly reviewed and updated based on emerging research and threat assessments.

Supportive Care: Managing Smallpox Symptoms

In the absence of a cure for smallpox, supportive care plays a crucial role in managing the disease and improving patient outcomes. What does supportive care for smallpox entail?

• Fluid replacement: Maintaining hydration is essential, particularly for patients with severe symptoms.
• Fever management: Antipyretic medications help control fever and alleviate discomfort.
• Pain relief: Analgesics are administered to manage pain associated with skin lesions and other symptoms.
• Nutritional support: Ensuring adequate nutrition is vital for maintaining the patient’s strength and supporting recovery.
• Infection control: Strict isolation measures prevent the spread of the virus to healthcare workers and other patients.
• Skin care: Proper management of skin lesions helps prevent secondary bacterial infections.

While these supportive measures cannot directly combat the virus, they play a crucial role in helping patients cope with the disease’s symptoms and potentially improve their chances of survival.

Vaccination Strategies: Balancing Risk and Protection

Given the eradication of smallpox, routine vaccination is no longer recommended for the general public. However, certain groups may still receive smallpox vaccination:

• Laboratory workers handling orthopoxviruses
• Healthcare personnel involved in smallpox preparedness and response teams
• Military personnel, as determined by the Department of Defense

In the event of a smallpox outbreak, how would vaccination be implemented?

Public health officials would likely employ a “ring vaccination” strategy. This approach involves:

1. Identifying confirmed cases of smallpox
2. Tracing and vaccinating close contacts of infected individuals
3. Expanding vaccination to broader circles of potential exposure
4. Implementing targeted vaccination of high-risk groups or geographic areas

This strategy aims to contain the spread of the virus while conserving vaccine supplies and minimizing potential adverse effects in the broader population.

Challenges in Smallpox Treatment Research

The development and testing of smallpox treatments face unique challenges due to the disease’s eradication. How do researchers evaluate potential therapies without active smallpox cases?

• Animal models: Researchers use related poxviruses to simulate smallpox infections in animals.
• In vitro studies: Laboratory experiments assess the ability of drugs to inhibit smallpox virus replication in cell cultures.
• Surrogate endpoints: FDA approval may be based on animal studies and safety data in humans, rather than direct efficacy against smallpox.
• Historical data: Researchers analyze records from past smallpox outbreaks to inform treatment strategies.

These approaches allow for the development of potential treatments while maintaining the ethical and practical constraints of working with an eradicated disease.

Future Directions in Smallpox Preparedness

As medical science advances, researchers continue to explore new avenues for smallpox prevention and treatment. What areas show promise for future developments?

• Next-generation vaccines: Researchers are working on safer, more effective smallpox vaccines with fewer side effects.
• Combination therapies: Investigating the potential of using multiple antiviral drugs together to enhance efficacy.
• Immunotherapies: Exploring the use of monoclonal antibodies or other immune-based treatments.
• Rapid diagnostics: Developing faster, more accurate tests to quickly identify smallpox cases in the event of an outbreak.
• Global surveillance: Enhancing international cooperation to monitor for potential smallpox re-emergence or related poxvirus threats.

These ongoing efforts ensure that the global community remains prepared to face the unlikely, but potentially catastrophic, re-emergence of smallpox.

Ethical Considerations in Smallpox Preparedness

The maintenance of smallpox virus stocks and continued research into treatments raise important ethical questions. What are some of the key ethical considerations surrounding smallpox preparedness?

• Dual-use research: Balancing the benefits of scientific inquiry against the potential risks of misuse.
• Resource allocation: Determining the appropriate level of investment in preparing for a disease that no longer naturally occurs.
• Global equity: Ensuring fair access to vaccines and treatments in the event of an outbreak.
• Informed consent: Addressing the challenges of testing treatments for a disease that doesn’t currently exist in human populations.
• Biosafety and biosecurity: Maintaining strict protocols to prevent accidental or intentional release of smallpox virus.

These ethical considerations shape policies and guide decision-making in smallpox preparedness efforts worldwide.

In conclusion, while smallpox remains eradicated, the global health community maintains vigilance through a multifaceted approach encompassing vaccines, antiviral drugs, supportive care strategies, and ongoing research. This comprehensive preparedness ensures that humanity stands ready to confront any potential re-emergence of this once-devastating disease.

Prevention and Treatment | Smallpox

There are vaccines to protect people from smallpox. Currently, smallpox vaccines are not recommended for the general public because smallpox has been eradicated. If there were a smallpox outbreak, health officials would use smallpox vaccines to control it. While some antiviral drugs may help treat smallpox disease, there is no treatment for smallpox that has been tested in people who are sick with the disease and proven effective.

Smallpox Vaccines

Smallpox can be prevented by smallpox vaccines, also called vaccinia virus vaccines. The vaccines are made from a virus called vaccinia, which is a poxvirus similar to smallpox, but less harmful. There are two licensed smallpox vaccines in the United States and one investigational vaccine that may be used in a smallpox emergency.

The replication-competent smallpox vaccines (ACAM2000 and APSV) can protect people from getting sick or make the disease less severe if they receive the vaccine either before or within a week of coming in contact with smallpox virus. If you get the vaccine:

• Before contact with the virus, the vaccine can protect you from getting sick.
• Within 3 days of being exposed to the virus, the vaccine might protect you from getting the disease. If you still get the disease, you might get much less sick than an unvaccinated person would.
• Within 4 to 7 days of being exposed to the virus, the vaccine likely gives you some protection from the disease. If you still get the disease, you might not get as sick as an unvaccinated person would.

Once you have developed the smallpox rash, the vaccine will not protect you.

Currently, smallpox vaccines are not available to the general public because smallpox has been eradicated, and the virus no longer exists in nature. However, there is enough smallpox vaccine to vaccinate every person in the United States if a smallpox outbreak were to occur.

For more details about the vaccine, see Smallpox Vaccine Basics.

Antiviral Drugs

• In July 2018, the FDA approved tecovirimat (TPOXX) for treatment of smallpox. In laboratory tests, tecovirimat has been shown to stop the 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 showed that it is safe and causes only minor side effects. In addition to treating smallpox disease, tecovirimat could also be used under an investigational new drug (IND) protocol to treat adverse reactions from vaccinia virus vaccination.
• In June 2021, the FDA approved brincidofovir (TEMBEXA) for treatment of smallpox. In laboratory tests, brincidofovir has been shown to stop the growth of the virus that causes smallpox and to be effective in treating animals that had diseases similar to smallpox. Brincidofovir has not been tested in people who are sick with smallpox, but it has been given to healthy people and people with other viral infections. Test results in people who received brincidofovir for bone marrow  transplants showed the most common side effects were diarrhea, nausea, vomiting, and abdominal pain.
• In laboratory tests, cidofovir has also been shown to stop the growth of the virus that causes smallpox and to be effective in treating animals that had diseases similar to smallpox. Cidofovir  has not been tested in people who are sick with smallpox, but has been tested in healthy people and in those with other viral illnesses. This drug continues to be evaluated for effectiveness and toxicity. Cidofovir is not FDA-approved for the treatment of variola virus infections, but  could be used during an outbreak under an appropriate regulatory mechanism (such as an investigational new drug [IND] protocol or Emergency Use Authorization).

Because these drugs were not tested in people sick with smallpox, it is not known if a person with smallpox would benefit from treatment with them. However, their use may be considered if there is ever a smallpox outbreak.

Tecovirimat and cidofovir are currently stockpiled by the Assistant Secretary for Preparedness and Response (ASPRexternal icon) Strategic National Stockpileexternal icon, which has medicine and medical supplies to protect the American public if there is a public health emergency, including one involving smallpox.

Treatment | Smallpox | CDC

Treatment of smallpox patients generally involves supportive care. Vaccination with replication-competent smallpox vaccines (i.e., ACAM2000 and APSV) can prevent or lessen the severity of disease if given within 2 to 3 days of the initial exposure. They may decrease symptoms if given within the first week of exposure.

Treating smallpox patients in a healthcare setting requires isolation and adherence to proper infection and environmental controls.

Antivirals

There are three primary antiviral therapies that have shown effectiveness against orthopoxviruses including variola (the virus that causes smallpox) in animals and in vitro studies. However, there is no treatment for smallpox disease that has been tested in people who are sick with the disease and been proven effective in this population.

Tecovirimat

In July 2018, the U.S. Food and Drug Administration (FDA) approved tecovirimat (also referred to as ST-246 or its brand name Tpoxx), the first drug with an indication for treatment of smallpox. Tecovirimat has been used in the treatment of severe adverse events to vaccinia virus vaccination; however, there are limited efficacy data in humans. Tecovirimat’s effectiveness against smallpox was established with in vitro studies using related orthopoxviruses as well as variola. Efficacy of tecovirimat treatment has also been demonstrated within multiple animal model studies measuring survival in animals infected with either variola virus or other closely related orthopoxviruses. Furthermore, treatment with tecovirimat minimized signs of morbidity as well as protected from mortality within prairie dogs challenged with monkeypox virus. The safety of tecovirimat was evaluated in 359 healthy human volunteers.

Tecovirimat was approved under the FDA’s Animal Rule, which allows efficacy findings from adequate and well-controlled animal studies to support an FDA approval when it is not feasible or ethical to conduct efficacy trials in humans. The FDA Antimicrobial Drugs Advisory Committee voted unanimously (17 to 0) that the benefits of tecovirimat treatment for smallpox outweigh its risks.

Brincidofovir

In June 2021, the FDA approved brincidofovir (also referred to its brand name TEMBEXA) for treatment of smallpox. Brincidofovir’s effectiveness against smallpox was established with in vitro studies using related orthopoxviruses as well as variola. Efficacy of brincidofovir treatment has also been demonstrated within multiple animal model studies measuring survival in animals infected with either variola virus or other closely related orthopoxviruses. The safety of brincidofovir was evaluated for non-smallpox indications, primarily in people who received  bone marrow transplants. Brincidofovir was approved under the FDA’s Animal Rule.

Cidofovir

In laboratory tests, cidofovir has been shown to be effective against the virus that causes smallpox and to be effective in treating animals that had diseases similar to smallpox. Cidofovir has not been tested in people who are sick with smallpox, but it has been tested in healthy people and in those with other viral illnesses. This drug continues to be evaluated for effectiveness and toxicity. It is not FDA-approved for the treatment of variola virus infections (smallpox), but it could be used during an outbreak under an appropriate regulatory mechanism (such as an investigational new drug [IND] protocol or Emergency Use Authorization).

Emergency Use of Smallpox Medical Countermeasures

During a declared public health emergency involving smallpox, CDC and the Assistant Secretary for Preparedness and Response (ASPRexternal icon) will provide more detailed guidance regarding the availability and use of smallpox medical countermeasures from the Strategic National Stockpileexternal icon under their appropriate regulatory mechanism(s) (e.g., IND, EUA, or Emergency Use Instructions [EUI]).

Rediscovered Native American remedy kills poxvirus | News

An old herbal remedy for treating smallpox that is thought to have been used by native Americans in the late 1800s has been rediscovered and found to kill the poxvirus. Smallpox has been eradicated, but the finding offers a possible treatment for poxvirus in the unlikely event of a bioterror attack or increased incidence of similar poxviruses such as monkey pox.  

Smallpox ravaged human populations for thousands of years, but in 1796 Edward Jenner discovered that exposure to cowpox lesions could provide immunity to smallpox. This led to the creation of the first vaccine for a disease. It took some time, but in 1979 the World Health Organization officially declared that smallpox had been eradicated. 

Historical sources suggest that in the 1800s, when smallpox still posed a serious threat, the Micmac native Americans of Nova Scotia treated the disease using a botanical infusion derived from the insectivorous plant Sarracenia purpurea, a species of pitcher plant.

Now, Jeffrey Langland at Arizona State University in Tempe, US, and colleagues have conducted in vitro experiments with the herbal extract and found it inhibits replication of the variola virus, the causative agent behind smallpox. 

Although, natural smallpox no longer poses a health threat, there is a remote possibility that unstable states or terrorist groups could have acquired stocks of the virus following the collapse of the Soviet Union, which had developed smallpox as a biological warfare agent.

Vaccinations are still administered to at risk groups including researchers working with poxviruses and members of the US military who could potentially be exposed to the virus through biological warfare. But since the risk is so low for populations at large, it is hard to justify vaccinating everyone, particularly because the vaccine can have serious side effects. Developing therapies is therefore important in order to treat people if a bioterror event does occur. 

’There is much scepticism on herbal medicine but what our results illustrate conclusively is that this herb is able to kill the virus and we can actually demonstrate how it kills the virus,’ says Langland. ’It takes this herb out of the realm of folklore, and into the area of true scientific evidence.’ 

The team made extracts of S. purpurea and found that it was highly effective at inhibiting the replication of the virus in rabbit kidney cells. They then looked at the replication cycle of the virus and found that the herb inhibits mRNA synthesis, halting production of proteins vital for replication. ’Other drugs are being developed against smallpox, but S. purpurea is the only known therapy that will target the virus at this point in the replication cycle,’ says Langland. 

’The extract blocks early transcription appearing to have a distinct mechanism of action from that of two other antivirals currently in clinical trials,’ says Mark Buller, a virologist at Saint Louis University, Missouri, US. ’The results are very compelling, and support the need to further evaluate the purified active ingredient in small animal studies.’ 

’With smallpox, it is obviously impossible to see if this herb is effective in the human body unless a bioterror release of the virus occurs,’ says Langland. ’We are in the process of doing animal studies to confirm our results in at least this type of whole animal system.’

Approach Considerations, Vaccination, Isolation Recommendations From the CDC

Author

Aneela Naureen Hussain, MD, MBBS, FAAFM Assistant Professor, Department of Family Medicine, State University of New York Downstate Medical Center; Consulting Staff, Department of Family Medicine, University Hospital of Brooklyn; Diplomate, American Board of Family Medicine

Aneela Naureen Hussain, MD, MBBS, FAAFM is a member of the following medical societies: American Academy of Family Physicians, American Medical Association, American Medical Women’s Association, Medical Society of the State of New York, Society of Teachers of Family Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Fazal Hussain, MD, MPH Associate Professor, Alfaisal University College of Medicine, Saudi Arabia

Fazal Hussain, MD, MPH is a member of the following medical societies: Aerospace Medical Association, American Academy of Pharmaceutical Physicians, American College of Radiation Oncology, American College of Radiology, American Public Health Association, American Society for Radiation Oncology, Association of Military Surgeons of the US, International College of Surgeons, New York State Radiological Society, Radiation Research Society, Royal Society for Public Health, Society of Clinical Research Associates

Disclosure: Nothing to disclose.

Maqsood Alam, MD Fellow, Department of Infectious Diseases, State University of New York Downstate Medical Center

Maqsood Alam, MD is a member of the following medical societies: American Medical Association, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Dennis J Cleri, MD, FACP, FIDSA, FAAM Chairman, Graduate Medical Education Committee, Professor of Medicine, Associate Professor of Infectious Diseases, Seton Hall University School of Graduate Medical Education; Director, Internal Medicine Residency Program, St Francis Medical Center

Disclosure: Nothing to disclose.

Chief Editor

John L Brusch, MD, FACP Corresponding Faculty Member, Harvard Medical School

John L Brusch, MD, FACP is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Acknowledgements

John L Brusch, MD, FACP Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance

John L Brusch, MD, FACP is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

David F Butler, MD Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Jeffrey P Callen, MD Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and American College of Rheumatology

Disclosure: Amgen Honoraria Consulting; Abbott Honoraria Consulting; Electrical Optical Sciences Consulting fee Consulting; Celgene Honoraria Safety Monitoring Committee; GSK – Glaxo Smith Kline Consulting fee Consulting; TenXBioPharma Consulting fee Safety Monitoring Committee

Dirk M Elston, MD Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Michael D Gober, MD Resident Physician, Department of Dermatology, Hospital of the University of Pennsylvania

Michael D Gober, MD is a member of the following medical societies: American Academy of Dermatology and American Medical Association

Disclosure: Nothing to disclose.

Duane R Hospenthal, MD, PhD Chief, Infectious Disease Service, San Antonio Military Medical Center, Brooke Army Medical Center; Professor of Medicine, Uniformed Services University of the Health Sciences

Duane R Hospenthal, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Armed Forces Infectious Diseases Society, Association of Military Surgeons of the US, Infectious Diseases Society of America, International Society for Infectious Diseases, International Society of Travel Medicine, and Medical Mycology Society of the Americas

Disclosure: Nothing to disclose.

William D James, MD Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System

William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology

Disclosure: elsevier Royalty Other; american college of physicians Honoraria Other

Julie R Kenner, MD, PhD Consultant, Clinical Research, Medical Affairs, VaxGen, Inc; Private Practice, Kenner Dermatology Center

Julie R Kenner, MD, PhD is a member of the following medical societies: American Academy of Dermatology and American Society of Tropical Medicine and Hygiene

Disclosure: Nothing to disclose.

Michelle Pelle, MD Clinical Assistant Professor, Division of Dermatology, Department of Medicine, University of California at San Diego

Michelle Pelle, MD is a member of the following medical societies: American Academy of Dermatology, California Medical Association, Medical Dermatology Society, and Pennsylvania Medical Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Victoria P Werth, MD Professor of Dermatology and Medicine, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, Philadelphia Veterans Affairs Medical Center

Victoria P Werth, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, American College of Rheumatology, Medical Dermatology Society, Phi Beta Kappa, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

FDA approves drug to treat smallpox

[6/4/2021] The U.S. Food and Drug Administration today approved Tembexa (brincidofovir) to treat smallpox. Although the World Health Organization declared smallpox, a contagious and sometimes fatal infectious disease, eradicated in 1980, there have been longstanding concerns that the virus that causes smallpox, the variola virus, could be used as a bioweapon.

Before its eradication in 1980, the variola virus mainly spread by direct contact among people. Symptoms typically began 10 to 14 days after infection and included fever, exhaustion, headache, and backache. A rash consisting of small, pink bumps progressed to pus-filled sores before it crusted over and scarred. Complications of smallpox included encephalitis (inflammation of the brain), corneal ulcerations (an open sore on the clear, front surface of the eye), and blindness.

Although naturally occurring smallpox no longer exists, concerns about potential uses of variola virus as a bioweapon has made smallpox drug development an important component of the U.S. medical countermeasures response.

Because smallpox is eradicated, the effectiveness of Tembexa was studied in animals infected with viruses that are closely related to the variola virus. Effectiveness was determined by measuring animals’ survival at the end of the studies. More animals treated with Tembexa survived compared to the animals treated with placebo. FDA approved Tembexa under the agency’s Animal Rule, which allows findings from adequate and well-controlled animal efficacy studies to serve as the basis of an approval when it is not feasible or ethical to conduct efficacy trials in humans.

Safety information to support approval of Tembexa was derived from clinical trials of the drug for a non-smallpox indication, primarily from patients who received hematopoietic stem cell transplants.  An increased risk of death was seen in another disease (Cytomegalovirus disease – a viral infection) when Tembexa was used for a longer-than-recommended duration (longer than once a week for two weeks on days 1 and 8). Tembexa is only approved for the treatment of smallpox.  

The most common side effects when using Tembexa are diarrhea, nausea, vomiting, and abdominal pain.

Tembexa received priority review, fast track and orphan drug designations. Priority review directs overall attention and resources to the evaluation of applications for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions when compared to standard applications. Fast track is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Orphan drug designation provides incentives to assist and encourage the development of drugs for rare diseases.  

Tembexa was developed in conjunction with the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA). FDA granted approval of Tembexa to Chimerix Inc.

Related Information

• Content current as of:

  06/04/2021

Smallpox | Michigan Medicine

Topic Overview

What is smallpox?

Smallpox is a contagious infection caused by the variola virus. Smallpox can be deadly, so if an outbreak happens, it is vital to stay away from infected people. Get vaccinated if you have been around someone who has smallpox. And if you have symptoms, seek medical care.

The telltale signs of smallpox are severe illness with a high fever, then a body rash. Symptoms appear about 12 days after the person is infected.

Before there was a vaccine, smallpox used to cause death all around the world. Thanks to widespread use of the vaccine, the last natural case of smallpox occurred in 1977. And in 1980 the World Health Organization (WHO) declared that the spread of smallpox was stopped and that the disease had been wiped out.

Because there is a slight risk of serious reactions and even death from the smallpox vaccine, routine smallpox immunization ended in the United States in 1972.

Smallpox virus is known to exist in labs at the Centers for Disease Control and Prevention (CDC) in the U.S. and at the State Research Center of Virology and Biotechnology in Russia. But it may also be in other labs. Some people worry that terrorists could release the virus and spread smallpox to many people.

What are the symptoms?

The first symptoms of smallpox include a high fever, fatigue, a headache, and a backache. After 2 to 3 days of illness, a flat, red rash appears. It usually starts on the face and upper arms, and then it spreads all over your body. Over the next 2 to 3 weeks, the flat, red spots become firm and dome-shaped and fill with pus. Then they scab over. Scabs fall off 3 to 4 weeks after the rash first appears, and they leave pitted scars.

The incubation period for smallpox is about 12 days. But symptoms can develop as soon as 7 days or as long as 19 days after exposure.

You may mistake a severe chickenpox rash for a smallpox rash at first. But different viruses cause these illnesses and there are many differences between chickenpox and smallpox rashes.

How is smallpox spread?

Smallpox is contagious. It can be passed from one person to another through coughing, sneezing, or breathing, or by contact with the scabs or the fluid from blisters. It can even spread from an infected person’s personal items and bedding. Smallpox is easiest to spread during the first week of the rash. As scabs form, the person is less contagious. But a person can spread the virus from the time the rash first appears until all scabs have fallen off.

If a terrorist were to release a small amount of the virus into the air, it is possible that it could spread among a large number of people. The virus may be able to survive and infect people for up to a day.

People who get this disease must stay away from others to help prevent it from spreading. If there has been a smallpox outbreak and you think you might have been exposed, call your doctor or local health department. Do not go directly to a health facility, because you could pass the disease to other people.

How is smallpox diagnosed?

If a doctor suspected a case of smallpox, blood and skin tests would be needed to confirm the diagnosis. A confirmed case of smallpox would be considered a worldwide health emergency. In the U.S., state and federal health officials would quickly take action. They would keep anyone who might have been exposed away from others.

If a smallpox outbreak had been confirmed, a doctor in the outbreak area could diagnose smallpox without a lab test. The doctor would look at the rash and ask about symptoms and possible exposure to the disease.

How is it treated?

There is no known cure for smallpox. Treatment includes drinking plenty of fluids and taking medicines to control pain and fever.

To prevent the spread of the virus, an infected person must be kept away from other people until he or she is no longer contagious.

Can smallpox infection be prevented?

People who have survived smallpox cannot get it again.

Also, there is a smallpox vaccination. It has vaccinia virus in it, which is like the smallpox virus but safer. If you get the shot before you’ve been exposed to smallpox, it will likely protect you for at least 3 to 5 years. And having a second shot later can protect you for an even longer period of time.

The shot works even if you don’t get it in advance. Most people who get the smallpox shot within 3 days after they’ve been exposed to the virus will have no symptoms or will have symptoms that aren’t as severe. Getting a shot 4 to 7 days after exposure may also help.^{footnote 1}

People who have very close contact with a person who has gotten a smallpox vaccine can get an infection from the virus used in the vaccine. The infection usually causes a minor skin rash and is not smallpox. So the site where the smallpox vaccine was given should be covered until the scab falls off.

In the past, when a smallpox infection was diagnosed, infected people were kept away from others to prevent the spread of infection. Everyone who might have been exposed to the virus was then vaccinated. This practice, called ring vaccination, played a key role in wiping out smallpox. Many experts think it would be better to carry out ring vaccination before mass vaccination if there were a case today.

Because there are risks of a serious reaction from the vaccine, routine smallpox immunization doesn’t occur. All children and most adults in the U.S. today have a chance of getting infected if they are exposed to the smallpox virus.

Since the September 2001 terrorist attacks on the U.S., more vaccine has been made. The U.S. government has enough smallpox vaccine for all Americans in case of an outbreak.^{footnote 1}

The smallpox vaccine is recommended for laboratory workers who handle the vaccinia virus, for members of smallpox response teams, and for certain people in the military. For accurate, up-to-date information, visit the Centers for Disease Control and Prevention (CDC) website at www.bt.cdc.gov/agent/smallpox.

Smallpox (variola) | DermNet NZ

Author: Vanessa Ngan, Staff Writer, 2003.

What is smallpox?

Smallpox is a highly contagious and sometimes deadly disease that is caused by infection with the variola virus. It has been around for thousands of years and has been associated with many deadly epidemics. Widespread vaccination between 1940 and 1970 has led to the global eradication of the virus and in 1980 the World Health Organization (WHO) officially declared smallpox eradicated. The last naturally occurring case of smallpox was in Somalia in 1977. The only remaining known variola virus isolates are stored at the Centers for Disease Control and Prevention (CDC) in the US and at the Vektor Institute in Russia. Renewed interest in smallpox is taking place, as there is concern that the variola virus may be used as an agent of bioterrorism.

There are 2 clinical types of smallpox, variola major and variola minor. Variola major is the most common and severe form and has a death rate of about 30%. Variola minor is a much less common form with an estimated death rate of less than 1%.

Vaccinia

Where does smallpox come from and how is it spread?

The variola virus emerged in human populations thousands of years ago and humans are the only natural host. Smallpox is most efficiently spread from one person to another by breathing in airborne respiratory droplets from an infected person. This generally requires direct and fairly prolonged face-to-face contact. It can also be spread by touching the skin rash, sores and scabs of an infected person, or by sharing contaminated clothing, towels or bedding.

What are the signs and symptoms of smallpox?

Infection with the variola virus begins with an incubation period that can be from 7-17 days (on average 12-14 days). During this time most people experience no symptoms whatsoever and they are not contagious. The first sign of smallpox disease is the prodromal phase, which lasts 2-4 days and is characterised by:

• Fever (> 40C)
• Malaise
• Severe headache
• Nausea and vomiting
• Aching body
• Sore throat
• Possibly contagious during this phase.

A characteristic rash appears after the prodromal phase and goes through several stages, lasting for up to 20 days or longer. The most contagious stage is the early rash, which lasts for about 4 days. Characteristics of this stage include:

• Small red spots occur on the tongue and in the mouth which turn into sores containing the virus
• Rash spreads to face, arms, legs, hands and feet and to all parts of the body within 24 hours (coincides with subsiding fever)
• The rash becomes raised bumps that then become fluid-filled with a depression in the centre (umbilicated)
• Fever recurs and stays high until scabs form
• A person is most contagious during this period, particularly when mouth sores have broken open and fill the mouth and throat with variola virus.

The bumps turn into pustules that are raised, round and firm to touch. Pustules may reach between 4 and 6 mm in diameter. After about 5 days pustules begin to form a crust and then scab. By about 3 weeks after the first signs of the rash appearing, scabs fall off leaving marks on the skin that eventually become pitted scars. A person is contagious until all the scabs have fallen off.

How is smallpox diagnosed?

Smallpox can be diagnosed clinically by the presence of fever and typical skin lesions. It is supported by isolation of the virus in the blood or skin lesions or the detection of antibodies to the variola virus in a bloodstream. These tests must be undertaken in specialised laboratories.

What is the differential diagnosis of smallpox?

Smallpox could be confused with several other diseases, especially:

• Chickenpox (varicella), usually seen in children and affecting the trunk predominantly
• Widespread shingles (zoster) in immune-compromised or elderly, normally starting in a single area of the body
• Impetigo, localised to one area and has honey-coloured crusts
• Severe cutaneous adverse reaction (SCAR) to a drug — a generalised rash after exposure to a medicine.

What is the treatment of smallpox?

There is no cure for smallpox. The aim of keeping smallpox under control is to prevent it from occurring. If smallpox is suspected in an individual, state health officials must be notified immediately and containment of the virus a major priority. This would include strict respiratory and contact isolation for at least 17 days and vaccination of all contacts.

Treatment for an already ill smallpox patient should be supportive care consisting of adequate hydration and nutrition, eye care and antibiotics as needed for secondary skin infections. Vaccination within the incubation period, particularly if given within 3 days of exposure to the virus, has been shown to prevent or significantly lessen the severity of smallpox disease in most people.

The patient should be isolated. Very strict adherence to hygiene and personal protective equipment (N95 mask, eye protection, gloves, and gown) must be worn by carers to reduce the chance of contagion.

What are the complications of smallpox?

Most patients who survive smallpox have extensive scarring of the skin. Other complications may include:

• Eye problems including corneal ulceration and blindness
• Bronchopneumonia
• Arthritis
• Osteomyelitis.

How is smallpox prevented?

Routine vaccination against smallpox among the general population was stopped soon after the WHO declared smallpox had been eradicated from the world. However, the last manufactured batches of smallpox vaccine (Vaccinia virus vaccine) are kept at the CDC, ready for use in the event of a smallpox outbreak. The United States has recently begun a vaccination programme for its military forces (February 2003).

Immunity is most effective during the first 10 years after vaccination and decreases thereafter. Historically, the vaccine has been effective in preventing smallpox infection in 95% of those vaccinated. The level of protection, in people who received the last routine smallpox vaccination over 30 years ago, is unclear.

Vaccination involves pricking the vaccine into a 5-mm area of the upper arm. The vaccination should be kept covered and should not be scratched, to avoid transmitting vaccinia virus to someone else. Within a few days, a papule appears that turns into a blister. It forms a pustule within a week, scabbing over in 2 weeks and healing with a scar within 3 weeks.

Unless recently exposed to smallpox, the following people should avoid vaccination as they are at greater risk of severe adverse effects.

• Pregnancy
• Immunodeficiencies
• Extensive skin disease eg burns, impetigo, dermatitis
• Immunosuppressive drugs eg cancer treatment, organ transplants
• Inflammatory eye disease (to avoid vaccinia entering eye)
• Allergy to a component of the vaccine (polymyxin B, streptomycin, chlortetracycline, neomycin)

What are the adverse effects of vaccination?

The complications of vaccination include:

• Soreness, redness, swelling and ulceration at the vaccination site
• Swollen lymph glands
• Fever, malaise, muscle aches
• No reaction: the subject should be revaccinated as it hasn’t taken
• Accidental implantation in another site or person
• Bacterial infection with Staphylococcus aureus or Group A beta-haemolytic Streptococci (impetigo)
• Erythema multiforme.

Severe adverse reactions to vaccination include:

• Severe accidental implantation reactions
• Generalised vaccinia: lesions appear on any part of the body for weeks to months (mild cases do not require VIG)
• Eczema vaccinatum arises in atopic dermatitis and results in extensive blistering, pustules and scarring
• Post-vaccinial encephalitis (15/million)
• Progressive vaccina: local spread from vaccination site then spreads throughout the body resulting in shock, secondary infection and death.

Severe adverse reactions require treatment with Vaccinia Immune Globulin (VIG). A new intravenous form is likely to replace an intramuscular form used during the 1960s.

90,000 Smallpox, sheep and goats

Smallpox of sheep and goats is a viral contagious disease characterized by fever, the formation of seals and nodules, vesicles on the skin, and the presence of lesions of internal organs. Source: sick animals and carriers of smallpox virus during the incubation period.The main routes of infection are aerogenic (through the air), contact and alimentary (through food).

Incubation period: 3 to 14 days.

Clinical signs

• depressed state;
• cessation of gum;
• conjunctivitis and swelling of the eyelids;
• the appearance of a rash on the head, legs, udder;
• chills and loss of appetite;
• hyperemia of the nasal mucosa;
• purulent-mucous discharge from the eyes;
• the appearance of scabs.

Diagnostics: based on clinical and epizootic data, results of laboratory blood tests.

Treatment: antibiotics, gamma globulins. The pockmarks on the skin are softened with neutral fats, ointments or glycerin, and the ulcerative surfaces are treated with iodine, 3-5% chloramine. The nasal cavity and conjunctiva are washed with warm water and irrigated with 2-3% boric acid solution. Animals are given water without restriction, adding potassium iodide to it.

Prevention and control measures

• Boil milk from sick individuals for at least 5 minutes.
• Cremation of fallen animals.
• Vaccination of clinically healthy animals.
• Establishment of quarantine.

Quarantine mode

• Isolation and treatment of sick and suspicious animals.
• Installation of disinfectants in the quarantine area.
• Installation of security and quarantine posts on the entrance and exit roads of the district.
• Prohibition of transportation and trade of animals and animal products.
• Prohibition of holding exhibitions, fairs, bazaars and other events related to the gathering of animals, people and vehicles in the quarantine area.

90,000 is the return of smallpox possible – RT in Russian

The last case of smallpox in the world was recorded on October 26, 1977. Today, a disease that once killed hundreds of thousands of people every year is considered conquered. Soviet doctors played a decisive role in eradicating this deadly virus.The idea that only global vaccination on a global scale will forever save people from smallpox was expressed in 1958 at the XI session of WHO by Academician Viktor Zhdanov. How vaccinations saved humanity from smallpox and other deadly diseases – in the material RT.

In old novels one can often find the following description of appearance: “Pockmarked face.” Those who survived after natural (or, as it is also called, blackpox) smallpox, forever had a mark – scars on the skin. They were formed due to the most characteristic feature of the disease – pockmarks, which appear on the body of patients.

Today, smallpox is no longer there, although it was once considered one of the worst diseases of mankind.

Smallpox epidemics

The first mentions of 90,065 smallpox outbreaks date back to the 6th century, but historians have suggested that some epidemics described by early chroniclers are similar to the same disease. For example, in the II century, during the reign of the emperor-philosopher Marcus Aurelius, a pestilence fell on Rome, the cause of which was probably smallpox. As a result, the troops were unable to resist the barbarians due to a shortage of soldiers: there was almost no one to recruit into the army – the disease struck a significant part of the empire’s population.

• Smallpox crusts on the patient’s hands
• © CDC / Dr. William Foege / Public Health Image Library

In full force, the disease hit humanity in the Middle Ages, when, due to poor hygiene, epidemics spread at lightning speed, mowing down cities and villages.

European countries suffered from smallpox until the twentieth century. In the 18th century, it was the main cause of death in European countries – smallpox even killed the Russian emperor Peter II.

The last serious outbreak of the disease in Western Europe happened in the 70s of the XIX century, then it claimed about half a million lives.

Europeans brought smallpox to other countries, and it killed no less Indians than the guns of the pale-faced. American colonists even used the disease as a biological weapon. There is a well-known story about how the indigenous people of the New World were presented with blankets infected with the smallpox virus. The Indians died from an unknown disease, and the colonists seized their lands.

Only the massive spread of vaccination put an end to the regular outbreaks of smallpox in developed countries.

Our victory

However, even after the massive spread of the vaccine in the 20th century, smallpox continued to take lives in the poor countries of Africa and Asia. Sometimes the disease “visited” and long-familiar places – for example, in Russia the last outbreak of smallpox was recorded in the late 1950s. The virus was brought by a tourist from India, three people died from the disease.

In 1958, at the XI session of the World Health Assembly, the Deputy Minister of Health of the USSR, Academician Viktor Zhdanov, expressed an incredibly courageous idea: smallpox can be defeated completely, this requires mass vaccination on a planetary scale.

• Scientist-virologist, epidemiologist, academician of the USSR Academy of Medical Sciences Viktor Mikhailovich Zhdanov
• RIA News
• © Vladimir Akimov

The idea of ​​a Soviet scientist was initially met with hostility by the World Health Organization: WHO Director General Morolino Kandau simply did not believe that such a thing was possible.Nevertheless, the Soviet Union, on its own initiative, began donating millions of doses of smallpox vaccine to WHO for distribution in Asia and Africa. It was only in 1966 that the organization adopted a program for the global eradication of smallpox. The leading role in it was played by Soviet epidemiologists who worked in the most remote corners of the world.

11 years after the start of the global vaccination program, on October 26, 1977, smallpox was last diagnosed in Somalia.

Finally, the disease was declared defeated at the XXXIII WHO conference in 1980.

What if he comes back?

Is the return of this deadly disease possible, the head of the laboratory for vaccine prevention and immunotherapy of allergic diseases at the I.I. Mechnikov Russian Academy of Medical Sciences, Professor Mikhail Kostinov.

“Viruses can come back, because virus strains are still stored in special laboratories in Russia and the USA.This is done just in case, in order to quickly create a new vaccine, if necessary, – said Kostinov. – The development of new vaccines against smallpox is still underway. So if, God forbid, there is such a need, then you can vaccinate. ”

Since the 70s of the twentieth century, people have not been vaccinated against smallpox, Kostinov noted, since the disease is considered to be eradicated, and “now a generation is being born that has no immunity from smallpox.”

According to the professor, all infections are controllable, they are controlled by vaccination.If it is not carried out, then the finally unconquered infection threatens to become uncontrollable, and this can lead to serious consequences, especially against the backdrop of calls here and there to refuse vaccinations.

• Smallpox vaccination
• Reuters
• © Jim Bourg

To date, humanity has defeated not only smallpox – the list of deadly diseases that have gone into the past is gradually expanding.Such sad companions of mankind as mumps, whooping cough or rubella are close to extinction in developed countries. Until recently, the polio virus vaccine had three serotypes (varieties). It has already been proven that one of them has been eliminated. And today the vaccine against this disease contains not three varieties of the strain, but two.

But if people refuse vaccines, the “leaving” diseases can return.

“Diphtheria is an example of the return of diseases,” Kostinov commented on the situation.- In the nineties, people massively refused to vaccinate, and the press also welcomed this undertaking. And in 1994-1996, there was no diphtheria anywhere on the planet, and only the former Soviet republics faced its epidemic. Experts from other countries came to see what diphtheria looks like! ”

Smallpox from the Empress, or the First Russian inoculation | History | DW

It was October 1768. In the magnificent palace of Tsarskoye Selo, Catherine the Second was secretly ill from everyone. And the physician of the Empress Dimsdale wrote in her diary with delight: “Many other pockmarks appeared and the smallpox was quite full, at will, to great pleasure.”His joy was simply explained: the empress, nee German princess Sophia von Anhalt-Zerbst, decided to test the then newfangled remedy for smallpox before introducing it in Russia, and the experiment was a success.

Few people managed to avoid smallpox and love.

Smallpox or smallpox began to rage in Europe from the 6th century. Whole cities died out. It was almost impossible to meet a city dweller without scars from healed smallpox ulcers on his face in those years. In France, in the 18th century, the police considered “the absence of traces of smallpox on the face” as one of the special signs.And the Germans used the saying “Von Pocken und Liebe bleiben nur Wenige frei” – “Few people manage to avoid smallpox and love.”

Catherine Palace. Tsarskoe Selo

The first method of controlling smallpox in Europe was variolation. As Professor Yuri Zobnin from St. Petersburg explains, the essence of the method was that biological material was extracted from the pockmarks of recovering patients, which was then artificially inoculated into healthy people. In the 18th century, they did it like this: they stretched an infected thread under the incised skin.

For Europe, variolation was opened by the wife of the British ambassador who returned to London from Turkey. But variolation did not give one hundred percent guarantee. And before Jenner’s invention, that is, before the vaccination of cowpox, which is not dangerous to humans, which everyone began to do en masse in the 20th century, there was still half a century. Therefore, in England they decided to test the reliability of the method by experimenting with criminals and children from orphanages. After that, the family of British King George I nevertheless decided on the infected thread.

Empress of Risk

And in Russia, smallpox epidemics took on a terrifying scale. This can be judged at least by the number of surnames that have survived to this day, the etymology of which goes back to nicknames: Ryabovs, Ryabtsevs, Ryabinins, Shchedrina, Shadrina, Koryavina. And the surname of the author of this article – Ryabko – is also from there. But experiments on checking variolation were not performed in Russia. Having learned about the vaccination, Empress Catherine II decided to try it first on herself.

Catherine was vaccinated against smallpox in secret, in the presence of only the most trusted confidants.”Vaccination of smallpox was considered a dangerous business, and the empress could not risk her health without the approval of the court,” says candidate of historical sciences Vadim Erlikhman. “The next day she went to Tsarskoe Selo, where she was treated for a week until she fully recovered. According to the official version, the material was taken from the servant of the sergeant Alexander Markov, six or seven years old, who then received the nobility and the surname Ospenny. ”

Judging by the doctor’s recollections, the empress behaved submissively: “On October 19, she slept and fell asleep all night, but sleep was interrupted many times.Head and back pain continued with fever. Hands were burning much more, and in the evening many pimples, merged together, appeared around the wounds. I didn’t want to eat all day, and didn’t deign to eat anything except a little tea, oatmeal and water in which apples were boiled. ”Then the heir Pavel Petrovich was vaccinated. – a doctor and a big pension ..

To be in fashion

But not a title, not a title or an estate, but a pockmark from the empress – this is what has become the dream of every courtier.According to Alexandra Bekasova, dean of the history department of the European University in St. Petersburg, shortly after the experiment, about 140 aristocrats were “inoculated” from Catherine.

Today such vaccinations are a common thing

“Now we have only two conversations: the first about the war (Russian-Turkish – author’s note), and the second about vaccination. Starting from me and my son, who is also recovering, there is no noble house , in which there were not several vaccinated, and many regret that they had smallpox and cannot be in fashion.Count Grigory Grigorievich Orlov, Count Kirill Grigorievich Razumovskaya and countless others went through the hands of Mr. Dimsdal, even to the beauties … England, Count Chernyshev

The example of Catherine can be called, in modern language, a PR-action, but we must not forget the risk she put her life at when she was the first to try vaccination on herself.And this risk was justified – not only for her, but for very many of her subjects.

90,000 Smallpox, diphtheria, poliomyelitis. Diseases We Conquer with Vaccines | Hromadske television

Vaccines are one of the most useful inventions of mankind. They have already saved hundreds of millions of lives and continue to do so. hromadske talks about some of the most impressive disease victories we owe to vaccines.

Smallpox: A Story of an Outright Victory

If you are under 40, then you are guaranteed not to have encountered this disease.Today, no one in any country in the world is sick with smallpox. And its pathogens are stored only in two very well-protected laboratories in the United States and Russia.

But in the twentieth century alone, smallpox claimed 300 million lives. This is the only infectious disease that has been completely eradicated. Vaccination has played a key role in the fight against it.

The first manifestations of smallpox are fever, severe weakness, back pain, vomiting and headache. On the second or third day, the temperature drops, and a rash appears on the human body.About a third of all patients eventually died. And those who survived received immunity and characteristic numerous scars on the skin, especially on the face.

It is known that people suffered from smallpox even before the beginning of the new era. In the 18th century in Europe, 400 thousand people died from it every year, and it was the cause of a third of all cases of blindness.

It was against smallpox that the first vaccine in history was created. And here we must pay tribute … to the cows.

The fact is that cows also get sick with their cowpox, and people can get it from them.Fortunately, no major health consequences.

More than two centuries ago, the English doctor Edward Jenner drew attention to the fact that milkmaids who were infected with cowpox from cows, then no longer fell ill with natural, that is, human.

In 1796 he conducted a historical experiment. A doctor infected an eight-year-old boy named James Phipps, the son of his gardener, with cowpox. He fell ill, but without any danger to his life. Some time later, they tried to infect the boy with natural smallpox, but nothing came of it, because he developed immunity against these diseases.Already at the beginning of the 19th century, the smallpox vaccine was successfully used in various countries.

But even in the 1950s, one and a half hundred years after its invention, about 50 million people in the world fell ill with smallpox every year. Therefore, in 1967, WHO launched a global smallpox control campaign. Thanks to her, 10 years ago – in 1977, the last case of the disease was registered in Somalia. The WHO was already ready to announce a complete victory over the disease, but an incident occurred that has not yet received an exhaustive explanation.

In 1978, Janet Parker, a photographer in the Anatomy Department of the University of Birmingham School of Medicine, fell ill with smallpox. The university did research the pathogen of smallpox, but other people did it, and none of them got sick. To avoid an outbreak of the disease, doctors urgently vaccinated about half a thousand people who could have come into contact with the patient. The outbreak was avoided, but Janet Parker herself died and became the last victim of smallpox in history.

Smallpox vaccination has not been carried out for four decades because it is not necessary. Smallpox can only affect people, so no other animal can serve as a “reservoir” for the causative agent of this disease.

There is no need to be afraid of the return of the disease, but such a danger cannot be excluded by 100%. For example, in 2014, in the US state of Maryland, in one of the scientific laboratories, several test tubes with the pathogen of smallpox were found, which were definitely not supposed to be there.Probably they were simply forgotten. Fortunately, this story had no negative consequences.

It is also impossible to exclude the possibility that the causative agent of the disease somehow falls into the hands of terrorists who use it as a biological weapon. To some, this may seem fantastic, but the United States, nevertheless, has a supply of smallpox vaccine. Fortunately, as a biological weapon, smallpox is far from the worst thing. Precisely because there is a vaccine and a cure for it.

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A healthcare professional administers a polio vaccine to a child at a clinic in Peshawar, Pakistan, December 1, 2020

Photo:

AP / Muhammad Sajjad

Poliomyelitis: the first candidate to fly out

The next infectious disease that humankind will eliminate can become polio.Most modern people also know about this terrible disease rather from textbooks, and this is very good.

The virus that causes poliomyelitis is easily transmitted by the oral and fecal route from person to person. At the same time, the vast majority of people do not notice it at all or get sick in a mild form.

But not everyone is so lucky: about one in two hundred patients develops paralysis. This is an irreversible process that can happen in a matter of hours. 10% of people with paralysis die.The most offensive thing is that the most vulnerable to polio are children under the age of 5.

There are three types of poliovirus. In 1999, the last case of infection with the second type of virus was registered, and 5 years ago, WHO officially announced its complete eradication. And in 2018, she announced the eradication of a type 3 virus that people have not been infected with since 2012. Only the first type remains. Fortunately, it can be eradicated as well as the other two.

There are two types of vaccines that were invented in the 1950s.According to WHO, they are one of the most important achievements of medicine of the last century. Despite the fact that the number of cases of polio has decreased significantly over the past decades, in countries such as Afghanistan and Pakistan, they still occur. And that’s bad news for everyone. Since the disease often goes away without symptoms, its pathogen can invisibly enter any country. Then any unimmunized person will be at risk.

Unfortunately, around polio vaccination, there are enough harmful myths that interfere with the fight against this terrible disease.For example, in Nigeria in the recent past, some religious leaders said that under the guise of vaccinations, doctors spread HIV and rendered women infertile. The result of such “preaching” is less vaccination coverage and subsequent outbreaks of the disease.

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A boy cries while receiving a diphtheria vaccine at a hospital in Sana’a, Yemen, September 9, 2019

Photo:

AP / Hani Mohammed

Diphtheria: one of the most dangerous childhood diseases

Children are always were most vulnerable to diphtheria.In the 1880s in the United States, the mortality rate from it in some regions reached 50%. In Europe, during the First World War, thanks to the success of medicine, this figure dropped to 15%. By the 1980s, in developing countries, about a million people were sick with it every year, 50-60 thousand of them died. Even today, the mortality rate for diphtheria can exceed 10%.

The causative agent of this disease is the bacterium Corynebacterium diphteriae . It releases exotoxin – a toxic substance that, once it enters the human body, becomes the main cause of all problems.

Diphtheria often goes away easily. But in some cases, it can affect the upper respiratory tract, heart muscle and kidneys. Sometimes a patient, in order to save his life, needs to do a tracheotomy (a surgical operation in which a hole is made in the trachea so that a person can breathe).

The diphtheria vaccine is one of the oldest used in medicine – it was created almost a hundred years ago. Its main component is toxoid – the same toxin that pathogens produce, but devoid of dangerous properties and capable of causing an immune response.

Children are vaccinated against diphtheria several times in order to develop strong immunity against the disease, and then in adulthood they are repeated every ten years. Its effectiveness is very high – from 92% to more than 99%, depending on the number of doses.

Thanks to the vaccine, the incidence of diphtheria has been significantly reduced. According to the WHO, 86% of children in the world receive the required three doses of the vaccine. But in some countries, for example, in Africa, this figure is less than 50%.

In Ukraine, according to the Ministry of Health, as of October 2019, the level of vaccination among children under one year old is only 59%, and adults – 52%.That is why we are still registering cases of this disease.

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Mothers with their children with measles at a hospital in Kuayoku, South Sudan, April 17, 2019

Measles: a story of a hybrid victory

Measles is another infectious disease from which, as well, as well as from diphtheria, children primarily suffer, especially under 5 years old. According to the WHO, in 2017, 110 thousand people died from it in the world. Before the introduction of the measles vaccine in the 1960s, the disease claimed an estimated 2.6 million lives annually.

Measles is a highly contagious viral disease. It can be infected by direct contact with the patient or through the air. It begins with a significant increase in temperature, which can last for 4-7 days. Patients may have a cough, runny nose, redness of the eyes. But one of the characteristic manifestations is a rash that appears on the face and upper neck, and then spreads throughout the body and lasts for 5-6 days.

Measles can cause serious complications – blindness, cerebral edema, diarrhea, which leads to dehydration, and pneumonia.They most often develop in children under 5 years of age or in adults over 30 years of age. It is with complications that deaths are most often associated. A person with measles is contagious 4 days before the rash appears and 4 days after the rash appears.

Although there is no specific treatment for measles, with proper care, the death rate from the disease does not exceed one percent. But without proper help, about one in ten dies. Unsurprisingly, more than 95% of all measles deaths occur in poor countries, primarily in Asia and Africa.

A turning point in the fight against this disease was the creation in the sixties of the last century of the vaccine, which is still the best way to prevent it. Besides, it is quite affordable – the cost of immunizing one child costs about one dollar.

The effectiveness of the vaccine can be inferred from the following figures. Already in 2000, measles deaths fell from the aforementioned 2.6 million per year in the middle of the century to 545 thousand cases. That is, about five times. And over the next 17 years – about five times more.The WHO notes that between 2000 and 2017 alone, vaccinations have saved more than 20 million lives.

But, unlike smallpox or the two types of poliovirus, the measles pathogen has not disappeared. People continue to get sick due to the fact that not all children receive this affordable and sufficiently safe vaccine. So, according to WHO, in 2017, 67% of children in the world received two doses (after the first vaccination, not everyone develops immunity). In Nigeria, Pakistan and other poor countries, this fact is easy to find a rational explanation.But in the case of Ukraine, where measles vaccinations are included in the national calendar, that is, they are given to everyone at the expense of the state, this is more difficult to do.

The fact is that for a long time in the 21st century, no more than 60% of our children were vaccinated against measles. As a result, in 2017-2019, an outbreak of measles occurred in Ukraine, when more than 115 thousand people fell ill, 39 of them died.

Fortunately, the situation returned to normal in 2020 and, according to the Public Health Center, 262 cases of measles were registered in 11 months – much less compared to the previous year.

“Humanity has become vaccinated”

Vaccine prophylaxis is the most effective means of combating the spread of viruses, which is known to mankind, Nikolai Briko, head of the Department of Epidemiology and Evidence-Based Medicine at Sechenov University (the university is a participant of the 5-100 Education Competitiveness Project), said in an interview with Izvestia. It was thanks to this procedure that in the last century people managed to cope with the deadliest pandemic, the culprit of which was smallpox.According to the scientist, in recent years, people have underestimated the role of vaccinations. However, refusal to vaccinate could lead to outbreaks of dangerous infections like poliomyelitis, which are now considered almost eradicated, the specialist warned.

– Why is it important to vaccinate for human survival?

– What are the main victories over diseases after the introduction of vaccine prevention?

– Of the most important achievements, I would single out the victories of mankind over polio, measles and especially smallpox.We have been smallpox-free for the fifth decade. Last year, on 8 May, we and WHO celebrated the 40th anniversary of smallpox eradication. Thanks to vaccinations, we have been able to overcome this disease on a global scale. Smallpox is one of the few anthroponotic infections (a disease whose causative agent is capable of parasitizing in natural conditions only in the human body. – Izvestia), which people have managed to literally hack to death everywhere. Thanks to the cooperation of many countries. Moreover, more than 3 thousand people coexisted with smallpox.years. In the 20th century alone, she killed about 300 million people.

– What share of the merit in the victory over smallpox belongs to the USSR?

– The fact that today’s world is free from a terrible disease that claimed the lives of hundreds of millions of people, devastated countries and continents is the merit of Soviet doctors. It was the USSR that proposed a program for the eradication of smallpox. It was in 1958 at the WHO World Assembly. Delegation of the Soviet Union led by Academician Viktor Zhdanov.Subsequently, about 1.5 billion doses of smallpox vaccine were produced in the USSR.

– If smallpox is defeated, why are new vaccines against this disease being created at the Vector Research Center?

– In Russia, new vaccines against smallpox are being developed not only at Vektor, but also at other institutes. They are needed because the drugs that were inoculated in the 1950s – 1960s can today give rise to severe complications – there are more immunocompromised people, people with an allergic disposition of the body.New drugs are also needed in case of an act of bioterrorism. Although there is no smallpox pathogen in nature, samples of the virus still remain on the planet. Officially, they are stored in two places: in the Koltsovo science city near Novosibirsk, and at the US Centers for Disease Control and Prevention. But we do not know for sure if the virus is not officially stored in laboratories in other countries.

– And after the smallpox case, were epidemiologists ever close to defeating infections?

– I would like to mention the fight against polio.In 2020, only 140 cases of infection were recorded. We can say that today poliomyelitis is practically eliminated. For comparison: in the pre-vaccine era, the incidence was at the level of 600 thousand cases per year. In addition, the case of polio is an example of the victory over the infection with some of the most dire consequences for human health. Poliomyelitis affects the spinal cord or brain and causes paralytic forms of the disease. Poliomyelitis, like smallpox, measles and many other viral diseases, is incurable.Etiotropic drugs (aimed at eliminating the cause of the disease. – Izvestia) for their effective treatment do not exist. Vaccination is the most effective way to prevent these diseases.

– Did Soviet scientists make a great contribution in this case too?

– Yes. Mass production of a vaccine against this infection based on Sabin’s live serum (talking about a live polio vaccine developed by the American scientist Albert Sabin.- “Izvestia”) was established in the Soviet Union with the participation of [the founder of the present Institute of Poliomyelitis and Viral Encephalitis named after V.I. M.P. Chumakov RAS] Mikhail Chumakov and [the founder of the N.I. A.A. Smorodintsev of the Ministry of Health of Russia] Anatoly Smorodintsev. The history of the fight against poliomyelitis is also a vivid example of the altruism of Soviet scientists. After all, the first versions of the drugs were tested by our specialists first on themselves and their relatives. The same Smorodintsev introduced one of the first doses of the vaccine to his beloved granddaughter. He took enormous risks to save the lives of millions of other children.This is a real feat.

– What vaccines, developed already in our time, would you single out?

– I would like to mention the drug for dengue fever, which is now going through the stages of clinical trials and research. The development of a vaccine against malaria is also a big event bordering on fantasy. After all, malaria is a disease, the causative agent of which is not a virus or even a bacterium. The drug was recently developed and is already being tested in several African countries.The latest advances in vaccine prevention are drugs against COVID-19. Today, more than 20 vaccines have been registered in the world, three of them are domestic.

The latest developments also include a vaccine against human papillomavirus infection. We know that papillomaviruses of certain genotypes – 16th and 18th – cause cervical cancer. At the same time, about 600 thousand cases of cervical cancer are registered annually. Papillomaviruses are generally responsible for a wide range of cancers in both men and women.Cancer of the larynx, cancer of the head and neck, cancer of the penis – papillomaviruses are often the culprits of these diagnoses.

– Which infections should not be overlooked despite the importance of addressing COVID-19?

– Pneumococcal infection is one of the most famous killers of children. Vaccination against this disease has been included in our national calendar since 2014. Since then, the incidence and mortality of pneumococcus among children has dropped sharply.But now the task is to create broad programs for vaccination of adults against pneumococcus. Indeed, for the elderly and people with chronic diseases, the disease is often fatal.

Meningococcal infection – right here. It is characterized by periods of decline and increase lasting 40-50 years. Now we are obviously in a period of another rise in the incidence. The pathogen causes terrible brain damage and is a frequent killer among children. Moreover, there is a vaccine against this infection.We need to start a mass vaccination program now.

– Why are many people in no hurry to get vaccinated against COVID-19, although throughout the history of mankind there has been a lot of convincing evidence about the benefits of vaccination?

– Today it is very important to popularize vaccination, because in recent years, not only during the COVID-19 pandemic, people’s confidence in this procedure has noticeably decreased. Because humanity has ceased to face powerful epidemics and pandemics.We just started to forget about the importance of vaccine prevention. Although vaccines remain the main tool that allows humanity to manage dangerous infections and even set goals for their elimination.

Vaccines have become hostages to their success. In the past, they have coped with many terrible infections, and people, against the background of well-being, have become less likely to use them. But this position is a big mistake. After all, the same poliomyelitis is now spread only in two countries: in Afghanistan and in Pakistan.However, it can easily spread beyond their borders. And if in the donor country the collective is not immune to the pathogen, an epidemic may begin.

– How long should vaccination against a particular disease continue on a regular basis?

– People are forced to continue vaccinations until the disease is eradicated. Yes, polio is practically non-existent today. In Russia, the last case was registered in 1996.But this result was achieved precisely thanks to the mass immunization of the population. It is possible to stop vaccination against a particular disease only if experts are convinced of the complete victory over the infection and the absence of circulation of the virus, as was the case with smallpox. In this sense, humanity has become vaccinated.

– What Russian vaccine against COVID-19 would you recommend to be vaccinated?

– All three Russian vaccines are highly effective.Therefore, everyone has the right to choose a drug for himself. Studies show that Sputnik V is the best vaccine against coronavirus among the three that are widely used in the world today. The Lancet reported over 91% efficiency. Recently, the developers of the vaccine made a presentation at the general meeting of the Russian Academy of Sciences, where the deputy director for scientific work of the Center. N.F. Gamalei Denis Logunov has already announced the 100% effectiveness of the drug in civilian use.

Chickenpox (chickenpox) – Lumen Vita

Every year from 1990 to 1994Before the chickenpox vaccine was available, there were about 4 million cases in the United States. Of this number, approximately 10,000 cases required hospitalization and 100 patients died.

Complications of chickenpox are recorded with a frequency of 5-6%, they are the reason for hospitalization in 0.3-0.5%. Of the total number of cases, this is several thousand per year. 30% of complications – neurological, 20% – pneumonia and bronchitis, 45% – local complications accompanied by the formation of scars on the skin

Mortality from chickenpox – 1 in 60,000 cases.

In 10-20% of those who have recovered, the varicella-zoster virus remains for life in the nerve ganglia and subsequently causes another disease that can manifest itself in old age – shingles or herpes

In response to vaccination, about 95% of children develop antibodies and 70-90% will be protected from infection for at least 7-10 years after vaccination. According to Japanese researchers (Japan is the first country in which a vaccine was registered), immunity lasts 10-20 years.

General

Chickenpox (chickenpox) is an acute, highly contagious viral disease prevalent throughout the world. As soon as one case occurs among susceptible individuals, it is very difficult to prevent an outbreak of the disease. While chickenpox is relatively mild in childhood, it becomes more severe in adults. It can be fatal, especially in newborns and in immunocompromised individuals.

The causative agent, varicella zoster virus (VZV), is transmitted by airborne droplets or by direct contact, and patients are usually contagious a few days before the onset of the rash and until the rash becomes crusted.Transmission of infection through third parties and household items is impossible.

VZV is a double-stranded DNA virus belonging to the herpesvirus family. Only one serotype is known, and man is its only reservoir.

The varicella-zoster virus VZV enters the human body through the mucous membrane of the nasopharynx and almost without exception causes clinical manifestations of the disease in susceptible individuals. After infection, the virus remains in a latent form in the nerve nodes and, as a result of VZV activation, can cause shingles (or herpes zoster – Herpeszoster ), a disease that mainly affects the elderly and those with weakened immune systems.

Probability of getting sick

The contagiousness of the varicella-zoster virus is truly unique – it is 100%. Chickenpox affects all age groups. However, this infection most often affects children. About half of childhood diseases occur at the age of 5 to 9 years, less often children 1–4 and 10–14 years old are ill. About 10% of the cases are people 14 years and older. Among this age group, over the past 5 years, the incidence of chickenpox has increased from 28 to 58 per 100 thousand.population. Children in the first months of life are most often resistant to this infection. However, children who are premature and weakened by other diseases can be seriously ill with chickenpox.

The maximum incidence of chickenpox is observed in the autumn-winter months. Epidemic outbreaks are observed mainly in organized groups among preschool children. Children attending kindergartens and nurseries have chickenpox 7 times more often than unorganized children.

The risk group also includes patients with immunodeficiencies, including HIV infection.Severe cases of chickenpox in children who received hormonal therapy with steroid drugs have been described. Also described are cases of congenital chickenpox in children whose mothers had chickenpox in the first half of pregnancy; perinatal infection occurs in children whose mothers become ill 5 days before and 48 hours after the birth of the child.

In persons with severe immunodeficiency of various etiologies (in rare cases with HIV infection and in patients after organ transplantation; often with acclimatization, decreased immunity caused by severe stress), repeated illness is possible.

Symptoms

The incubation period is usually 14-16 (10-21) days. After chickenpox, the virus remains in sensory ganglia, where it can later reactivate and cause herpes zoster. Symptoms of chickenpox appear as an itchy vesicular rash that usually begins on the face and upper body and is initially accompanied by fever and general malaise. The presence of a vesicular rash on the scalp is a characteristic symptom of chickenpox.The elements of the rash look like small (several millimeters in diameter) bubbles rising above the reddened surface of the skin, filled with a clear liquid (which contains the varicella-zoster virus). As the rash gradually spreads to the body and limbs, the first bubbles (vesicles) dry out. Usually all crusts disappear after 7-10 days.

Complications after a previous illness

Although varicella (chickenpox) is a relatively benign childhood illness and is rarely considered a significant public health problem, the course of the disease can sometimes be complicated by pneumonia or encephalitis caused by the VZV virus, which can be permanent or fatal.The most dangerous are bullous, hemorrhagic or gangrenous forms of chickenpox. Disfiguring scars can form as a result of secondary infection of the vesicles; in addition, necrotizing fasciitis or sepsis may result from such infection.

Complications of chickenpox are recorded with a frequency of 5-6%, they serve as a reason for hospitalization in 0.3-0.5% of patients. Of the total number of cases, this is several thousand per year. 30% of complications are neurological, 20% are pneumonia and bronchitis, 45% are local complications (for example, streptaderma), accompanied by the formation of scars on the skin.

Other serious manifestations include pneumonia (more often in adults), rarely – congenital chickenpox syndrome (caused by chickenpox transferred during the first 20 weeks of pregnancy) and perinatal chickenpox of newborns whose mothers develop chickenpox in the period 5 days before and 48 hours after childbirth. In patients with immunodeficiencies, including HIV infection, chickenpox is severe. Severe chickenpox and deaths can also occur in children taking steroid hormones for asthma.In general, complications and deaths from chickenpox are more common in adults than in children.

In 10-20% of those who have recovered, the varicella-zoster virus remains for life in the nerve ganglia and subsequently causes another disease that can manifest itself at an older age – shingles or herpes (Herpes zoster). Herpes zoster is characterized by lingering and excruciating neuralgic pain, and also has a number of complications in the form of lesions of the nervous system and internal organs – paralysis, visual impairment.People with herpes zoster can be a source of chickenpox infection.

Mortality

The mortality rate (deaths per 100,000 cases) among healthy adults is 30-40 times higher than among children aged 5-9 years. The mortality rate is 1 in 60,000 cases.

Treatment

Treatment of chickenpox is mainly reduced to the prevention of bacterial complications. To avoid the spread of the virus, good hygiene must be followed, including daily showers and nail clipping in young children (to prevent scratching and rupture of the rash blisters).

The use of antiviral agents during treatment, such as acyclovir, is justified only for premature infants, patients with impaired immune systems and adults (due to the greater severity of the infection). The traditional remedy for the “treatment” of chickenpox – “brilliant green” – is not in any way effective, much more effective than baths and baths with a small addition of soda, antihistamines and pain relieving ointments to relieve itching.

Effectiveness of vaccination

Apart from vaccination, there are no countermeasures to control the spread of chickenpox or the incidence of shingles in a susceptible population.Varicella zoster immunoglobulin and herpes medicines are very expensive and are mainly used for prophylaxis after contact with an infection or for the treatment of chickenpox in people at high risk of developing a severe form of the disease. Due to the extreme contagiousness of chickenpox in the world, almost all children or young adults get sick. Every year from 1990 to 1994, before the chickenpox vaccine was introduced, there were about 4 million cases in the United States. Of this number, approximately 10,000 patients required hospitalization and 100 patients died.

Chickenpox vaccines obtained using the Oka strain of the VZV virus have been on the market since 1994. The positive results in terms of safety, efficacy and cost-benefit analysis have confirmed the validity of their implementation in childhood immunization programs in a number of industrialized countries. After observing study populations for 20 years in Japan and 10 years in the United States, more than 90% of immunocompetent individuals vaccinated during childhood still had protection against chickenpox.

In response to vaccination, about 95% of children develop antibodies, and 70-90% will be protected from infection for at least 7-10 years after vaccination. According to Japanese researchers (Japan is the first country in which a vaccine was registered), immunity against chickenpox lasts 10-20 years. It is safe to say that the circulating virus contributes to the “revaccination” of the vaccinated, increasing the duration of immunity.

Research shows that emergency vaccination can be effective – when the vaccine is given within 96 hours (preferably 72 hours) of exposure to VZV, at least 90% protective efficacy can be expected.Treatment for chickenpox is much easier for people who have received the vaccine than for those who have not been vaccinated.

Vaccines

The chickenpox vaccines currently available on the market are obtained using the so-called VZV Oka strain, which has been modified by sequential reproduction in various cell cultures. Various formulations of these live, attenuated vaccines have been rigorously tested and approved for use in Japan, the Republic of Korea, the United States, and several European countries.Some vaccines are approved for use by ages 9 months or older.

From a logistical and epidemiological point of view, the optimal age for varicella vaccination is 12-24 months. In Japan and several other countries, one dose of the vaccine is considered sufficient, regardless of age. In the United States, 2 doses of the vaccine given 4-8 weeks apart are recommended for adolescents and adults, of whom 78% seroconverted after the first dose and 99% after the second dose.

According to the current US vaccination schedule, children receive 2 doses of the vaccine (1st dose at 12 months, 2nd at 6 years old).

More about vaccines

Recent epidemics

The incidence of chickenpox is widespread throughout the world. In Russia, there is an annual increase in the number of diseases of this infection. From 1998 to 2007, the incidence of chickenpox increased 1.8 times annually, every year 500-700 thousand cases of chickenpox are recorded.

An interesting fact: the chickenpox vaccine became available in the Russian Federation in 2009.From the end of 2013 to 2015, there was a break in the supply of vaccines to our country. According to Rospotrebnadzor, in 2015 there was an increase in the incidence of chickenpox compared to 2014 by 16%.

Historical information and interesting facts

Chickenpox was first described in Italy in the middle of the 16th century by the physicians Vidus-Vidius and Ingranus. For a long time, chickenpox was not recognized as an independent disease and was considered a type of natural smallpox. After the causative agent of chickenpox was discovered in the contents of the chickenpox vesicles in 1911, the disease began to be considered a separate nosological form.The virus itself was isolated only in 1958. The varicella-zoster virus infects only humans; humans are also the only reservoir of infection.

90,000 Smallpox, sheep and goats | Veterinary clinic

Smallpox of sheep and goats (Latin – Variola ovina; English – Sheep pox) is a highly contagious especially dangerous disease characterized by fever and the formation of papular-pustular lesions in the epithelium of the skin and mucous membranes.

Causative agent of the disease DNA is a containing virus belonging to the Poxviridae family, genus Capripoxvirus.All strains of sheep pox virus isolated in different countries are antigenically identical. The virus is cultivated in the primary and subculture of kidney and testicle cells of lambs, kids and calves.

Epizootology . Sheep of all ages and breeds, especially fine-wooled sheep, are ill. Under natural conditions, sheep are more likely to become infected when healthy animals come into contact with sick animals. Sick animals scatter the virus in the external environment with drying out and rejecting smallpox crusts. The virus, secreted with mucus from the nose, can be transmitted to healthy sheep by airborne transmission.An alimentary route of infection is not excluded when the virus enters the mucous membrane of the oral cavity, since it often has damage from roughage. A serious danger is posed by recovered sheep, in which the pathogen can persist in dry crusts for several months. When the mammary gland is damaged, the virus is excreted in milk. In fresh epizootic foci, the incidence of smallpox can reach more than 50% of the number of sheep. The regular mass prophylactic immunizations carried out in recent years have influenced the intensity of the manifestation of the epizootic process.Smallpox is reported sporadic in most cases, regardless of the season. Smallpox mortality is low – up to 3 … 5%.

Pathogenesis. The virus that enters the body with the inhaled air multiplies in the epithelial cells of the respiratory tract, causing typical changes. From here, it is carried by the bloodstream into the skin and mucous membranes, in which it causes the formation of pockmarks. During the period of viremia, when fever is observed, the pathogen is found in the blood, lungs and kidneys.

Course and clinical manifestation. The incubation period lasts 4 … 14 days. The manifestation of the disease begins with swelling of the eyelids and the appearance of serous-mucous and serous-purulent discharge from the eyes and nose. Breathing is difficult and accompanied by a sniffing noise. Smallpox rash is more often found on the head, lips, around the eyes, on the inner surface of the front and hind limbs, on the scrotum and foreskin in males, as well as on the skin of the udder and mucous membrane of the pudendal lips in females.Initially, the rash looks like round pinkish specks with slight edema around the periphery. After 1 … 2 days, the spots turn into dense, rounded papules, surrounded by a towering red belt. They are rapidly increasing in size. Body temperature, previously elevated (up to 40 … 41 ° C), decreases slightly. After 1 … 3 days, the epidermis on the periphery of the papules rises. At this time, the papules are impregnated with a transparent, slightly yellowish serous fluid. More than 90% of diseased sheep have pelliculated papules, characterized by different sizes and dark red swelling of the skin.As papules form, they turn pale, becoming gray-white or gray-yellow with a pink rim. At this time, the epidermis is easily separated in the form of a film (pellicle, skin). Sometimes a lot of papules appear, in which case they merge. Vesicles and pustules usually do not form. In the affected areas of the skin under the scab, connective tissue scars are formed, which, depending on the degree of tissue damage, are weakly overgrown or not covered with hair at all. The scab falls off after 5 … 6 days. If the smallpox process is complicated, the signs of secondary infections, accompanied by lesions of the respiratory tract and the gastrointestinal tract, come to the fore.With a severe course of smallpox, exanthema covers large areas of the skin: individual papules, merging with each other, form continuous lesions of significant areas of the skin that are subject to purulent inflammation. The disease is accompanied by a significant increase in body temperature, especially during the period of suppuration, and a deterioration in the general condition of the animal. This form of smallpox is called confluent. Most often, the confluent form of smallpox is observed in lambs. 50 … 80% of diseased individuals (young animals) die, more often from sepsis. With a mild and abortive course of smallpox, a small number of pockmarks appear on the body of animals, the body temperature rises slightly, and pockmarks, without undergoing all stages of formation, can quickly disappear.

Pathological signs. In addition to the characteristic changes in the skin and mucous membranes of the oral cavity, hemorrhagic inflammation of the mucous membrane of the gastrointestinal tract and respiratory tract is found. Erosions and ulcers are found in the pharynx and trachea. An increase in all superficial and regional lymph nodes is noted. Hemorrhages are observed on the serous integuments; in the lungs – foci of hepatization. In the sections of papules, stained according to Pashen and Romanovsky, elementary particles of the virus are detected – the virions of the causative agent of the disease.

Diagnostics and differential diagnostics. The diagnosis of smallpox is made on the basis of the analysis of epizootological, clinical, pathological data and the results of laboratory studies, including a bioassay.

Immunity, specific prophylaxis. Recovered animals acquire immunity for at least 2 years. For the specific prophylaxis of sheep pox, a culture virus-vaccine from an attenuated strain of the Institute of Agriculture is used, which creates immunity in vaccinated animals for up to 12 months.

Prevention. To prevent the occurrence of sheep pox, it is necessary: ​​1) to prevent the introduction (import) of sheep into the farm, as well as feed and equipment from farms that are dysfunctional for sheep pox; 2) keep all sheep that have come to the farm in isolation for 30 days; 3) maintain pastures, drinking places, livestock buildings in proper veterinary and sanitary condition; 4) the sheep population of farms and settlements in the area threatened by sheep pox should be regularly vaccinated with smallpox vaccine.

Treatment. Specific treatments for patients with sheep pox have not been developed.

Control measures. In the event of sheep pox, a quarantine is imposed on the farm, under the conditions of which it is prohibited: entry and import into a disadvantaged point, removal and removal of animals of all types from it, regrouping of animals within the farm, as well as grazing, watering and keeping sick sheep together with healthy animals of all species; removal of forage from a dysfunctional point, with which sick sheep came into contact; shearing; trade in animals and livestock products, holding exhibitions, fairs, bazaars and other events related to the accumulation of animals in the quarantined territory; travel of all types of transport; access of people not related to the service of animals in disadvantaged groups; use of uncontaminated sheep’s milk.

In farms dysfunctional for sheep pox, all the sheep livestock, regardless of their affiliation, are registered and subjected to clinical examination once every 10 days. Detected sick sheep are isolated and, if necessary, treated with symptomatic agents. The corpses of sheep that have died in the presence of clinical signs of smallpox are burned. All clinically healthy sheep are vaccinated against smallpox. The vaccinated animals must be monitored by veterinarians for 14 days. When identified among the vaccinated population of patients, they are transferred to a separate group and treated.

After each case of death of sheep and cleaning of corpses, as well as at the end of immunization of sheep, all livestock buildings, pens and other places where animals are located are subjected to mechanical cleaning followed by disinfection. Given the high resistance of the smallpox virus in the external environment and the non-simultaneous illness of animals, disinfection is repeated every 5 days during the entire quarantine period. For disinfection of premises, hot solutions of alkali, sulfur-carbolic mixture, 20% solution of freshly slaked lime (calcium hydroxide), clarified solution of bleach or sodium hypochlorite, formaldehyde solution are used.Walls, fences and various wooden fences should be decontaminated with a freshly prepared quicklime solution. Manure is disinfected within 3 weeks using a biothermal method.

In the event of the appearance of sheep pox in areas where it has not been recorded for 3 years or more, immediate slaughter of all sheep of the dysfunctional group (patients suspected of the disease and suspected of being infected) is necessary. Slaughter is carried out on a specially equipped slaughter site in compliance with veterinary and sanitary rules.

The sanitary assessment of meat and other products of slaughter is carried out in accordance with the requirements of the veterinary and sanitary examination. The skins obtained during the slaughter of sheep are disinfected in a solution of carbolic acid or creolin emulsion for 24 hours, and then dried. The export of sheepskins is allowed only after the quarantine has been lifted.

Wool and other raw materials of animal origin, harvested before the quarantine was established, are disinfected in a steam disinfection chamber at a temperature of 110 ° C, and then, after the quarantine is lifted, they are taken out in a container made of dense fabric to processing plants.