Tag: vaccination

All about Monkeypox & its Relation to Smallpox

The clinical presentation of monkeypox resembles that of smallpox, a related orthopoxvirus infection which has been eradicated. Smallpox was more easily transmitted and more often fatal as about 30% of patients died. The last case of naturally acquired smallpox occurred in 1977, and in 1980 smallpox was declared to have been eradicated worldwide after a global campaign of vaccination and containment. It has been 40 or more years since all countries ceased routine smallpox vaccination with vaccinia-based vaccines. As vaccination also protected against monkeypox in West and Central Africa, unvaccinated populations are now also more susceptible to monkeypox virus infection. Whereas smallpox no longer occurs naturally, the global health sector remains vigilant in the event it could reappear through natural mechanisms, laboratory accident or deliberate release. To ensure global preparedness in the event of reemergence of smallpox, newer vaccines, diagnostics and antiviral agents are being developed. These may also now prove useful for prevention and control of monkeypox.

How monkeypox relates to smallpox

The clinical presentation of monkeypox resembles that of smallpox, a related orthopoxvirus infection which has been eradicated. Smallpox was more easily transmitted and more often fatal as about 30% of patients died. The last case of naturally acquired smallpox occurred in 1977, and in 1980 smallpox was declared to have been eradicated worldwide after a global campaign of vaccination and containment. It has been 40 or more years since all countries ceased routine smallpox vaccination with vaccinia-based vaccines. As vaccination also protected against monkeypox in West and Central Africa, unvaccinated populations are now also more susceptible to monkeypox virus infection.

Whereas smallpox no longer occurs naturally, the global health sector remains vigilant in the event it could reappear through natural mechanisms, laboratory accident or deliberate release. To ensure global preparedness in the event of reemergence of smallpox, newer vaccines, diagnostics and antiviral agents are being developed. These may also now prove useful for prevention and control of monkeypox.

Key facts

  • Monkeypox is caused by monkeypox virus, a member of the Orthopoxvirus genus in the family Poxviridae.
  • Monkeypox is a viral zoonotic disease that occurs primarily in tropical rainforest areas of Central and West Africa and is occasionally exported to other regions.
  • Monkeypox typically presents clinically with fever, rash and swollen lymph nodes and may lead to a range of medical complications.
  • Monkeypox is usually a self-limited disease with the symptoms lasting from 2 to 4 weeks. Severe cases can occur. In recent times, the case fatality ratio has been around 3-6%.
  • Monkeypox is transmitted to humans through close contact with an infected person or animal, or with material contaminated with the virus.
  • Monkeypox virus is transmitted from one person to another by close contact with lesions, body fluids, respiratory droplets and contaminated materials such as bedding.
  • The clinical presentation of monkeypox resembles that of smallpox, a related orthopoxvirus infection which was declared eradicated worldwide in 1980. Monkeypox is less contagious than smallpox and causes less severe illness.
  • Vaccines used during the smallpox eradication programme also provided protection against monkeypox. Newer vaccines have been developed of which one has been approved for prevention of monkeypox
  • An antiviral agent developed for the treatment of smallpox has also been licensed for the treatment of monkeypox.

WHO- Monkeypox

WHO- Monkeypox

Introduction

Monkeypox is a viral zoonosis (a virus transmitted to humans from animals) with symptoms very similar to those seen in the past in smallpox patients, although it is clinically less severe. With the eradication of smallpox in 1980 and subsequent cessation of smallpox vaccination, monkeypox has emerged as the most important orthopoxvirus for public health. Monkeypox primarily occurs in Central and West Africa, often in proximity to tropical rainforests and has been increasingly appearing in urban areas. Animal hosts include a range of rodents and non-human primates.

The pathogen

Monkeypox virus is an enveloped double-stranded DNA virus that belongs to the Orthopoxvirus genus of the Poxviridae family. There are two distinct genetic clades of the monkeypox virus – the Central African (Congo Basin) clade and the West African clade. The Congo Basin clade has historically caused more severe disease and was thought to be more transmissible. The geographical division between the two clades has so far been in Cameroon – the only country where both virus clades have been found.

Natural host of monkeypox virus

Various animal species have been identified as susceptible to monkeypox virus.. This includes rope squirrels, tree squirrels, Gambian pouched rats, dormice, non-human primates and other species. Uncertainty remains on the natural history of monkeypox virus and further studies are needed to identify the exact reservoir(s) and how virus circulation is maintained in nature.

Outbreaks

Human monkeypox was first identified in humans in 1970 in the Democratic Republic of the Congo in a 9-year-old boy in a region where smallpox had been eliminated in 1968. Since then, most cases have been reported from rural, rainforest regions of the Congo Basin, particularly in the Democratic Republic of the Congo and human cases have increasingly been reported from across Central and West Africa.

Since 1970, human cases of monkeypox have been reported in 11 African countries – Benin, Cameroon, the Central African Republic, the Democratic Republic of the Congo, Gabon, Cote d’Ivoire, Liberia, Nigeria, the Republic of the Congo, Sierra Leone, and South Sudan. The true burden of monkeypox is not known. For example, in 1996–97, an outbreak was reported in the Democratic Republic of the Congo with a lower case fatality ratio and a higher attack rate than usual. A concurrent outbreak of chickenpox (caused by the varicella virus, which is not an orthopoxvirus) and monkeypox was found which could explain real or apparent changes in transmission dynamics in this case. Since 2017, Nigeria has experienced a large outbreak, with over 500 suspected cases and over 200 confirmed cases and a case fatality ratio of approximately 3%. Cases continue to be reported until today.

Monkeypox is a disease of global public health importance as it not only affects countries in West and Central Africa, but the rest of the world. In 2003, the first monkeypox outbreak outside of Africa was in the United States of America and was linked to contact with infected pet prairie dogs. These pets had been housed with Gambian pouched rats and dormice that had been imported into the country from Ghana. This outbreak led to over 70 cases of monkeypox in the U.S. Monkeypox has also been reported in travelers from Nigeria to Israel in September 2018, to the United Kingdom in September 2018, December 2019, May 2021 and May 2022, to Singapore in May 2019, and to the United States of America in July and November 2021. In May 2022, multiple cases of monkeypox were identified in several non-endemic countries. Studies are currently underway to further understand the epidemiology, sources of infection, and transmission patterns.  

Transmission

Animal-to-human (zoonotic) transmission can occur from direct contact with the blood, bodily fluids, or cutaneous or mucosal lesions of infected animals. In Africa, evidence of monkeypox virus infection has been found in many animals including rope squirrels, tree squirrels, Gambian poached rats, dormice, different species of monkeys and others. The natural reservoir of monkeypox has not yet been identified, though rodents are the most likely. Eating inadequately cooked meat and other animal products of infected animals is a possible risk factor. People living in or near forested areas may have indirect or low-level exposure to infected animals.

Human-to-human transmission can result from close contact with respiratory secretions, skin lesions of an infected person or recently contaminated objects. Transmission via droplet respiratory particles usually requires prolonged face-to-face contact, which puts health workers, household members and other close contacts of active cases at greater risk. However, the longest documented chain of transmission in a community has risen in recent years from six to nine successive person-to-person infections. This may reflect declining immunity in all communities due to cessation of smallpox vaccination. Transmission can also occur via the placenta from mother to fetus (which can lead to congenital monkeypox) or during close contact during and after birth. While close physical contact is a well-known risk factor for transmission, it is unclear at this time if monkeypox can be transmitted specifically through sexual transmission routes. Studies are needed to better understand this risk.

Signs and symptoms

The incubation period (interval from infection to onset of symptoms) of monkeypox is usually from 6 to 13 days but can range from 5 to 21 days.

The infection can be divided into two periods:

  • the invasion period (lasts between 0-5 days) characterized by fever, intense headache, lymphadenopathy (swelling of the lymph nodes), back pain, myalgia (muscle aches) and intense asthenia (lack of energy). Lymphadenopathy is a distinctive feature of monkeypox compared to other diseases that may initially appear similar (chickenpox, measles, smallpox)
  • the skin eruption usually begins within 1-3 days of appearance of fever. The rash tends to be more concentrated on the face and extremities rather than on the trunk. It affects the face (in 95% of cases), and palms of the hands and soles of the feet (in 75% of cases). Also affected are oral mucous membranes (in 70% of cases), genitalia (30%), and conjunctivae (20%), as well as the cornea. The rash evolves sequentially from macules (lesions with a flat base) to papules (slightly raised firm lesions), vesicles (lesions filled with clear fluid), pustules (lesions filled with yellowish fluid), and crusts which dry up and fall off. The number of lesions varies from a few to several thousand. In severe cases, lesions can coalesce until large sections of skin slough off.

Monkeypox is usually a self-limited disease with the symptoms lasting from 2 to 4 weeks. Severe cases occur more commonly among children and are related to the extent of virus exposure, patient health status and nature of complications. Underlying immune deficiencies may lead to worse outcomes. Although vaccination against smallpox was protective in the past, today persons younger than 40 to 50 years of age (depending on the country) may be more susceptible to monkeypox due to cessation of smallpox vaccination campaigns globally after eradication of the disease.  Complications of monkeypox can include secondary infections, bronchopneumonia, sepsis, encephalitis, and infection of the cornea with ensuing loss of vision. The extent to which asymptomatic infection may occur is unknown.

The case fatality ratio of monkeypox has historically ranged from 0 to 11 % in the general population and has been higher among young children. In recent times, the case fatality ratio has been around 3-6%.

Diagnosis

The clinical differential diagnosis that must be considered includes other rash illnesses, such as chickenpox, measles, bacterial skin infections, scabies, syphilis, and medication-associated allergies. Lymphadenopathy during the prodromal stage of illness can be a clinical feature to distinguish monkeypox from chickenpox or smallpox.

If monkeypox is suspected, health workers should collect an appropriate sample and have it transported safely to a laboratory with appropriate capability. Confirmation of monkeypox depends on the type and quality of the specimen and the type of laboratory test. Thus, specimens should be packaged and shipped in accordance with national and international requirements. Polymerase chain reaction (PCR) is the preferred laboratory test given its accuracy and sensitivity. For this, optimal diagnostic samples for monkeypox are from skin lesions – the roof or fluid from vesicles and pustules, and dry crusts. Where feasible, biopsy is an option. Lesion samples must be stored in a dry, sterile tube (no viral transport media) and kept cold. PCR blood tests are usually inconclusive because of the short duration of viremia relative to the timing of specimen collection after symptoms begin and should not be routinely collected from patients.

As orthopoxviruses are serologically cross-reactive, antigen and antibody detection methods do not provide monkeypox-specific confirmation. Serology and antigen detection methods are therefore not recommended for diagnosis or case investigation where resources are limited. Additionally, recent or remote vaccination with a vaccinia-based vaccine (e.g. anyone vaccinated before smallpox eradication, or more recently vaccinated due to higher risk such as orthopoxvirus laboratory personnel) might lead to false positive results.

In order to interpret test results, it is critical that patient information be provided with the specimens including: a) date of onset of fever, b) date of onset of rash, c) date of specimen collection, d) current status of the individual (stage of rash), and e) age.

Therapeutics

Clinical care for monkeypox should be fully optimized to alleviate symptoms, manage complications and prevent long-term sequelae. Patients should be offered fluids and food to maintain adequate nutritional status. Secondary bacterial infections should be treated as indicated.  An antiviral agent known as tecovirimat that was developed for smallpox was licensed by the European Medical Association (EMA) for monkeypox in 2022 based on data in animal and human studies. It is not yet widely available.

If used for patient care, tecovirimat should ideally be monitored in a clinical research context with prospective data collection.

Vaccination

Vaccination against smallpox was demonstrated through several observational studies to be about 85% effective in preventing monkeypox. Thus, prior smallpox vaccination may result in milder illness. Evidence of prior vaccination against smallpox can usually be found as a scar on the upper arm. At the present time, the original (first-generation) smallpox vaccines are no longer available to the general public. Some laboratory personnel or health workers may have received a more recent smallpox vaccine to protect them in the event of exposure to orthopoxviruses in the workplace. A still newer vaccine based on a modified attenuated vaccinia virus (Ankara strain) was approved for the prevention of monkeypox in 2019. This is a two-dose vaccine for which availability remains limited. Smallpox and monkeypox vaccines are developed in formulations based on the vaccinia virus due to cross-protection afforded for the immune response to orthopoxviruses.

Prevention

Raising awareness of risk factors and educating people about the measures they can take to reduce exposure to the virus is the main prevention strategy for monkeypox. Scientific studies are now underway to assess the feasibility and appropriateness of vaccination for the prevention and control of monkeypox. Some countries have, or are developing, policies to offer vaccine to persons who may be at risk such as laboratory personnel, rapid response teams and health workers.

 

Reducing the risk of human-to-human transmission

Surveillance and rapid identification of new cases is critical for outbreak containment. During human monkeypox outbreaks, close contact with infected persons is the most significant risk factor for monkeypox virus infection. Health workers and household members are at a greater risk of infection. Health workers caring for patients with suspected or confirmed monkeypox virus infection, or handling specimens from them, should implement standard infection control precautions. If possible, persons previously vaccinated against smallpox should be selected to care for the patient.

Samples taken from people and animals with suspected monkeypox virus infection should be handled by trained staff working in suitably equipped laboratories. Patient specimens must be safely prepared for transport with triple packaging in accordance with WHO guidance for transport of infectious substances.

The identification in May 2022 of clusters of monkeypox cases in several non-endemic countries with no direct travel links to an endemic area is atypical. Further investigations  are underway to determine the likely source of infection and limit further onward spread. As the source of this outbreak is being investigated, it is important to look at all possible modes of transmission in order to safeguard public health. Further information on this outbreak can be found here

 

Reducing the risk of zoonotic transmission

Over time, most human infections have resulted from a primary, animal-to-human transmission. Unprotected contact with wild animals, especially those that are sick or dead, including their meat, blood and other parts must be avoided. Additionally, all foods containing animal meat or parts must be thoroughly cooked before eating.

Preventing monkeypox through restrictions on animal trade

Some countries have put in place regulations restricting importation of rodents and non-human primates. Captive animals that are potentially infected with monkeypox should be isolated from other animals and placed into immediate quarantine. Any animals that might have come into contact with an infected animal should be quarantined, handled with standard precautions and observed for monkeypox symptoms for 30 days.

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History & Evolution of Vaccination


Before the first vaccinations, in the sense of using cowpox to inoculate people against smallpox, people have been inoculated in China and elsewhere, before being copied in the west, by using smallpox, called Variolation.

Variolation was the method of inoculation first used to immunize individuals against smallpox (Variola) with material taken from a patient or a recently variolated individual, in the hope that a mild, but protective, infection would result.

   The procedure was most commonly carried out by inserting/rubbing powdered smallpox scabs or fluid from pustules into superficial scratches made in the skin. 

    The earliest hints of the practice of variolation for smallpox in China come during the 10th century. The Chinese also practiced the oldest documented use of variolation, which comes from Wan Quan’s (1499–1582) Douzhen Xinfa  of 1549. They implemented a method of “nasal insufflation” administered by blowing powdered smallpox material, usually scabs, up the nostrils.

   Various insufflation techniques have been recorded throughout the sixteenth and seventeenth centuries within China. Two reports on the Chinese practice of inoculation were received by the Royal Society in London in 1700; one by Martin Lister who received a report by an employee of the East India Company stationed in China and another by Clopton Havers. In France, Voltaire reports that the Chinese have practiced variolation “these hundred years”.

     In 1796, Edward Jenner, a doctor in Berkeley in Gloucestershire, England, tested a common theory that a person who had contracted cowpox would be immune from smallpox. To test the theory, he took cowpox vesicles from a milkmaid named Sarah Nelmes with which he infected an eight-year-old boy named James Phipps, and two months later he inoculated the boy with smallpox, and smallpox did not develop.

   In 1798, Jenner published An Inquiry into the Causes and Effects of the Variolae Vacciniae which created widespread interest. He distinguished ‘true’ and ‘spurious’ cowpox (which did not give the desired effect) and developed an “arm-to-arm” method of propagating the vaccine from the vaccinated individual’s pustule. Early attempts at confirmation were confounded by contamination with smallpox, but despite controversy within the medical profession and religious opposition to the use of animal material, by 1801 his report was translated into six languages and over 100,000 people were vaccinated. The term vaccination was coined in 1800 by the surgeon Richard Dunning in his text Some observations on vaccination.

   In 1802, the Scottish physician Helenus Scott vaccinated dozens of children in  Mumbai (previous Bombay) against smallpox using Jenner’s cowpox vaccine. In the same year Scott penned a letter to the editor in the Bombay Courier, declaring that “We have it now in our power to communicate the benefits of this important discovery to every part of India, perhaps to China and the whole eastern world”.  Subsequently, vaccination became firmly established in British India. A vaccination campaign was started in the new British colony of Ceylon in 1803.

    By 1807 the British had vaccinated more than a million Indians and Sri Lankans against smallpox. Also in 1803 the Spanish Balmis Expedition launched the first transcontinental effort to vaccinate people against smallpox. Following a smallpox epidemic in 1816 the Kingdom of Nepal ordered smallpox vaccine and requested the English veterinarian William Moorcroft to help in launching a vaccination campaign. In the same year a law was passed in Sweden to require the vaccination of children against smallpox by the age of two. Prussia briefly introduced compulsory vaccination in 1810 and again in the 1920s, but decided against a compulsory vaccination law in 1829.

    A law on compulsory smallpox vaccination was introduced in the Province of Hanover in the 1820s. In 1826, in Kragujevac,  future prince Mihailo of Serbia was the first person to be vaccinated against smallpox in the principality of Serbia. 

    Following a smallpox epidemic in 1837 that caused 40,000 deaths, the British government initiated a concentrated vaccination policy, starting with the Vaccination Act of 1840, which provided for universal vaccination and prohibited Variolation.

    The Vaccination Act 1853 introduced compulsory smallpox vaccination in England and Wales.

    The law followed a severe outbreak of smallpox in 1851 and 1852. It provided that the poor law authorities would continue to dispense vaccination to all free of charge, but that records were to be kept on vaccinated children by the network of births registrars. It was accepted at the time, that voluntary vaccination had not reduced smallpox mortality,  but the Vaccination Act 1853 was so badly implemented that it had little impact on the number of children vaccinated in England and Wales. 

In the United States of America compulsory vaccination laws were upheld in the 1905 landmark case Jacobson v. Massachusetts by the Supreme Court of the United States. The Supreme Court ruled that laws could require vaccination to protect the public from dangerous communicable diseases. However, in practice the United States had the lowest rate of vaccination among industrialized nations in the early 20th century.

    Compulsory vaccination laws began to be enforced in the United States after World War II. In 1959 the World Health Organization (WHO) called for the eradication of smallpox worldwide, as smallpox was still endemic in 33 countries.

     In the 1960s six to eight children died each year in the United States from vaccination-related complications. According to the WHO there were in 1966 about 100 million cases of smallpox worldwide, causing an estimated two million deaths.

     In the 1970s there was such a small risk of contracting smallpox that the United States Public Health Service recommended for routine smallpox vaccination to be ended.

   By 1974 the WHO smallpox vaccination program had confined smallpox to parts of Pakistan, India, Bangladesh, Ethiopia and Somalia.

     In 1977 the WHO recorded the last case of smallpox infection acquired outside a laboratory in Somalia. In 1980 the WHO officially declared the world free of smallpox.

   In 1974 the WHO adopted the goal of universal vaccination by 1990 to protect children against six preventable infectious diseases: measles, poliomyelitis, diphtheria, whooping cough, tetanus, and tuberculosis.

    In the 1980s only 20 to 40% of children in developing countries were vaccinated against these six diseases. In wealthy nations the number of measles cases had dropped dramatically after the introduction of the measles vaccine in 1963. WHO figures demonstrate that in many countries a decline in measles vaccination leads to a resurgence in measles cases. Measles are so contagious that public health experts believe a vaccination rate of 100% is needed to control the disease.  Despite decades of mass vaccination polio remains a threat in India, Nigeria, Somalia, Niger, Afghanistan, Bangladesh and Indonesia.

   By 2006 global health experts concluded that the eradication of polio was only possible if the supply of drinking water and sanitation facilities were improved in slums. The deployment of a combined DPT vaccine against diphtheria, pertussis (whooping cough), and tetanus in the 1950s was considered a major advancement for public health. But in the course of vaccination campaigns that spanned decades, DPT vaccines became associated with high incidences of side effects. Despite improved DPT vaccines coming onto the market in the 1990s, DPT vaccines became the focus of anti-vaccination campaigns in wealthy nations. As immunization rates decreased, outbreaks of pertussis increased in many countries.

      In 2000, the Global Alliance for Vaccines and Immunization was established to strengthen routine vaccinations and introduce new and under-used vaccines in countries with a per capita GDP of under US$1000.

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