Neurologic Complications of Smallpox and Monkeypox: A Review

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Review

. 2022 Nov 1;79(11):1180-1186.

doi: 10.1001/jamaneurol.2022.3491.

B Jeanne Billioux 
¹
, Oliver Tshiani Mbaya 
²
, James Sejvar 
³
, Avindra Nath 
¹

Affiliations

Affiliations

• ¹ National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
• ² Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of Congo.
• ³ Centers for Disease Control and Prevention, Atlanta, Georgia.

• PMID:

  36125794

• DOI:

  10. 1001/jamaneurol.2022.3491

Review

B Jeanne Billioux et al.

JAMA Neurol.

2022.

. 2022 Nov 1;79(11):1180-1186.

doi: 10.1001/jamaneurol.2022.3491.

Authors

B Jeanne Billioux 
¹
, Oliver Tshiani Mbaya 
²
, James Sejvar 
³
, Avindra Nath 
¹

Affiliations

• ¹ National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
• ² Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of Congo.
• ³ Centers for Disease Control and Prevention, Atlanta, Georgia.

• PMID:

  36125794

• DOI:

  10.1001/jamaneurol.2022.3491

Abstract

Importance:

Orthopox viruses include smallpox virus, a once feared but now eradicated virus, as well as monkeypox virus. Monkeypox is an emerging virus initially isolated in 1958, previously unrecognized outside sub-Saharan Africa until a worldwide outbreak in May 2022. It is important to review known neurologic consequences of both these viruses, as complications of smallpox may be relevant to monkeypox, though complications of monkeypox may be rarer and perhaps less severe.

Observations:

This was a literature review of the known neurologic complications of smallpox, which include encephalitis, transverse myelitis, and acute disseminated encephalomyelitis among others; historical complications of smallpox vaccination, including postvaccinal encephalomyelitis; and the known neurologic complications of monkeypox, which include headaches and mood disturbances, as well as rare presentations of encephalitis, transverse myelitis, and seizures. Of concern is the possibility of viral persistence and systemic complications in immunocompromised individuals. Also provided were considerations for diagnosis, current treatment, and prevention of monkeypox.

Conclusions and relevance:

Monkeypox should be considered in high-risk populations who present with neurologic syndromes. Diagnosis may require serology and polymerase chain reaction testing of blood and spinal fluid. Antiviral therapy should be initiated early in the course of the illness.

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Smallpox

Written by Rebecca Buffum Taylor

• What Is Smallpox?
• Smallpox Symptoms
• Smallpox Causes
• How Smallpox Is Spread
• Smallpox Diagnosis
• Smallpox Treatment
• Smallpox Complications
• Smallpox Vaccine
• Risks of the Smallpox Vaccine
• Smallpox as a Public Health Threat
• More

Smallpox is a contagious disease caused by a virus that’s no longer found in nature. For centuries, smallpox killed millions of people around the world. But thanks to global immunization programs, the deadly infectious disease was wiped out in the late 1970s.

Today, scientists keep only a small amount of the virus alive under tightly controlled conditions in the U.S. and Russia for medical research.

Routine smallpox vaccinations stopped in the U.S. and in many other countries in 1972, and in all other World Health Organization member countries by 1986. Many adults living today likely got the vaccine as children.

Smallpox gets its name from its most common sign of the disease: small blisters that pop up on the face, arms, and body, and fill up with pus.

Other symptoms include:

• Flu-like fatigue
• Headache
• Body aches
• Intense back pain
• Some vomiting
• High fever
• Mouth sores and blisters that spread the virus into the throat
• A skin rash that gets worse in a typical pattern:
  • The rash starts with flat red sores that become raised bumps a few days later.
  • The bumps turn into fluid-filled blisters.
  • The blisters fill with pus.
  • They crust over, usually in the second week of smallpox.
  • Scabs form over the blisters and then fall off, usually in the third week of the disease. They can cause permanent scars.
• Blindness can happen when blisters form near the eyes.

The variola virus causes it. There are two forms of the virus. The more dangerous form, variola major, led to smallpox disease that killed about 30% of people who were infected. Variola minor caused a less deadly type that killed about 1% of those who got it.

Two forms of smallpox were more deadly than the common strain: Hemorrhagic and malignant.

Hemorrhagic smallpox tended to affect adults, including pregnant women, not children. People had more serious symptoms, including fever, pain, and headaches, and they leaked blood from their blisters and mucous membranes. People usually died of blood poisoning within a week.

Malignant smallpox tended to affect children, not adults. Instead of raised blisters, people developed flat lesions that merged on the skin surface. Most people who got this form of smallpox also died of blood poisoning.

The disease is highly contagious. You could get it:

• By breathing in the virus during close, face-to-face contact with an infected person. It usually spreads through drops of saliva when the person coughs, sneezes, or speaks.
• By handling the clothes or sheets of an infected person or coming into contact with their body fluids.
• Very rarely, smallpox has spread among people in small, enclosed spaces, probably through air in the ventilation system. Animals and insects don’t spread the disease.
• If the virus were spread through an act of terrorism. This is a rare possibility, but in case it happens, governments around the world have stockpiled smallpox vaccines.

Because smallpox hasn’t been diagnosed in decades, it’s likely that doctors wouldn’t recognize the disease in patients right away. It’s possible to diagnose the condition by testing a sample of tissue taken from a smallpox blister. A single diagnosis would be considered a worldwide health emergency.

There’s only one known drug that can treat smallpox. The drug tecovirimat (TPOXX) was approved in 2018 for the treatment of smallpox should someone show symptoms of the virus. The drug cidofovir has also worked well in early studies. Getting the vaccine within 3 to 4 days of contact with the virus may make the disease less severe or may help prevent it.

Beyond that, medical care aims to ease symptoms like fever and body aches, and control any other illnesses that a person can get when their immune system is weak. Antibiotics can help if someone gets a bacterial infection while they have smallpox.

If people got hemorrhagic or malignant smallpox, they would be more likely to die. The more fatal forms of the disease are more likely to affect women who are pregnant and people whose immune systems are impaired.

People who survive smallpox may be scarred on the face and body. In rare cases, they may become blind. Smallpox may also cause infertility in men, and it may cause miscarriage or stillbirths in women.

Scientists use the cousin virus to variola — the vaccinia virus — to make the smallpox vaccine, because it poses fewer health risks. The vaccine prompts the body’s immune system to make the tools, called antibodies, it needs to protect against the variola virus and help prevent smallpox disease.

No one knows for sure how long the smallpox vaccine protects people from the disease. Some experts believe it lasts for up to 5 years and wears off over time. Since it may not give lifelong protection, anyone vaccinated years ago as a child could be at risk of future infection by the variola virus. The only people known to be immune for life are those who have had smallpox and survived.

The World Health Organization and its member countries keep an emergency stockpile of the smallpox vaccine. It’s rarely used today, except for those few people who are around the variola virus, such as laboratory researchers working with variola and viruses like it.

Some of its side effects can be dangerous, especially for people with weak immune systems. They can range from skin reactions to a serious nervous system condition called encephalitis, which can lead to convulsions, coma, and death. But these side effects are very rare. Based on historical data, for every 1 million people vaccinated for smallpox, one to two people died from a bad reaction.

Some people would have a higher risk of a reaction to the vaccine, like:

• Women who are pregnant or breastfeeding
• People with skin disorders such as eczema
• People with a weak immune system due to a medical condition like leukemia or HIV
• People on medical treatments, such as for cancer, that make the immune system weak

It’s hard to know how major a threat a smallpox outbreak would be today. There are a few reasons that scientists can’t be sure:

• The number of people around the world with weakened immune systems is higher today than when smallpox existed.
• Countries used vaccines of different strengths during the global effort to end smallpox.
• There’s no way to know for sure how long these different vaccinations give immunity to the virus.

If an outbreak of smallpox were to happen, public health measures would likely include these steps: find and vaccinate infected people, vaccinate health care workers and others at risk of infection, isolate smallpox patients to keep them from spreading the disease, and give vaccinations for the public as needed to contain the outbreak.

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Chickenpox

Viral disease characterized by moderate general intoxication, benign course, rash in the form of vesicles.

Who is sick?

Children aged 5–9 who attend kindergarten or school are more likely to get sick.

Who is the source of infection?

The virus is transmitted from a sick person to a healthy person by airborne droplets (when talking, staying in one small room). With a current of air, chickenpox can spread over long distances (up to 20 m).

What are the main clinical signs?

For chickenpox, temperatures up to 39°C may occur. The most striking manifestation is the appearance of a characteristic rash in the form of vesicles, usually filled with transparent contents. Initially, the elements of the rash appear on a small area of ​​the body (usually the scalp, face), then the rash spreads over the entire surface of the body, and mucous membranes can also be affected. In the future, the bubbles open, forming ulcers, in place of which crusts form.

Why is the disease dangerous? Chickenpox

Among the complications of chickenpox, the most common are various purulent skin lesions – abscesses, boils, phlegmon with the addition of a bacterial infection. Less common complications: encephalitis, myocarditis, pneumonia, keratitis, nephritis, arthritis, hepatitis.

How to treat the disease?

In case of a mild course of the disease, treatment is carried out at home, under the supervision of a physician. With

severe forms and the appearance of complications, the child must be hospitalized.

How to prevent disease?

The most effective means of prevention is vaccination.

When is vaccination given?

Vaccination against chickenpox is carried out for children from 12 months of age, primarily from risk groups – before entering preschool educational organizations, children from orphanages, contact persons from the foci of the disease, who have not been ill, not vaccinated and do not have information about preventive vaccinations against chickenpox, persons subject to conscription for military service, children going on vacation to summer recreational institutions. Vaccination is carried out twice with a minimum interval of 6 weeks.

What vaccines are used?

Varilrix is ​​a live attenuated varicella vaccine1.

What are the possible complications of the vaccine?

Local reactions: pain, swelling and redness at the injection site. Short-term fever, any rash that is not like chickenpox itself, rarely a rash similar to chickenpox.

Significantly rare: inflammation of the lymph nodes, irritability, headache, drowsiness, runny nose, cough, muscle and joint pain.

What are the contraindications for vaccination?

▪ Hypersensitivity to any component of the vaccine, including neomycin

▪ Symptoms of hypersensitivity to previous administration of Varilrix vaccine

▪ Primary or acquired immunodeficiency

▪ Pregnancy 90 005

1 Live attenuated – a vaccine in which pathogens are specially weakened and are not able to cause

visible signs of the disease, but retain the ability to form the body’s immune response

ways of infection, possible complications and methods of treatment

The causative agent of chicken pox belongs to the ubiquitous but small family of herpes viruses. All members of the family cause skin lesions in herpes simplex, genital herpes, cytomegalovirus infection, and herpes zoster. All of them, and chickenpox is no exception, begin to penetrate from the mucous membranes, and then for the rest of a person’s life they hide in the nervous tissue, coming to the surface in the form of herpetic eruptions.

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How and why does chickenpox get infected?

The source of the disease is a sick person during the formation of a rash. It is not necessary to meet with the patient himself, it is enough to get a drop of saliva with a live virus floating in the air when coughing or talking.

The cause of the disease is the varicella-zoster virus getting into the mucous membrane of the upper respiratory tract, where it immediately penetrates into the epithelial cell, multiplies and travels with the bloodstream to the lymph nodes, and then throughout the body.

How to detect varicella-zoster virus?

The majority suffers chickenpox in kindergarten, susceptibility to an infectious agent is almost 96%, so chickenpox in adults is very rare, and its course is mostly atypical. Symptoms are either too pronounced or almost not expressed, just not the classic version.

Often the infection is mistaken for an allergic reaction, when no blisters appear, the process stops at the stage of spots. Often, symptoms of severe intoxication come to the fore, while the rash is subtle. The overall reaction is aggravated by concomitant chronic diseases and age-related decline in immunity.

Infection specialists of the international clinic Medica24 diagnose pathology and help to cope with symptoms that worsen the quality of life.

The time from infection to the appearance of the first symptoms of the disease takes 10 – 21 days, but more often within 2 weeks.

The disease begins acutely, the onset – the prodromal period – takes about two days. There are no characteristic symptoms at the onset of chickenpox, just intoxication. But in every third adult, the disease begins with pronounced manifestations: fever, headache, nausea, pain in the abdomen and lower back.

In some cases, the first symptoms of chickenpox may be catarrhal symptoms: sore throat, runny nose and dry cough.

The most characteristic sign of chickenpox

This is a rash that occurs on non-inflamed skin. First, a rapidly growing speck appears, its center gradually rises, and a bubble grows in it, like a drop of dew. The liquid in it soon becomes cloudy, and already on the 3rd day a crust forms. Bubbles of different sizes, from a point to a centimeter. The bubble will not necessarily grow, it may remain in the speck stage.

New bubbles appear in several stages, there are no more than four such waves with a break of a day or two, and for about a week it regularly “sprinkles” new ones. For the entire period of the rash, it takes no more than 3 weeks, on the third, crusts mainly form. There are no scars left.

Where can chicken pox appear?

First on the trunk and limbs, but not on the hands and feet, and then on the face and head. It also happens in the mouth, causing pain when chewing and salivation, the bubbles open easily, forming erosions that heal in 3 days. Bubbles also appear on the mucous membrane of the genital organs. Papules also grow in the eye, are transferred quite easily, the vesicle quickly opens, forming an ulcer, which disappears without a trace in a couple of days.

In the international clinic Medica24, an examination is carried out using high-precision equipment, which allows you to quickly make the correct diagnosis and immediately begin treatment.

What are the other symptoms of chickenpox?

When the rash develops, the temperature rises, the rash comes in waves and the fever also comes in waves, but the temperature rarely lasts more than 5 days. With an extremely profuse rash, high fever and drowsiness, convulsions and loss of consciousness are possible. The rash, of course, is very itchy.

Nearly half have enlarged lymph nodes on the neck and in the submandibular areas, which almost never occurs in children. The well-being of adults suffers more than that of children, and the severity of clinical manifestations is more intense.

How does the infection usually proceed?

Mild course with few rashes, normal or briefly rising to 38°C, blisters disappear in 3 days.

In case of moderate infection with temperature up to 39°С, abundant skin formations disappear within 5 days.

Severe chickenpox occurs in patients weakened by chronic diseases, a fresh rash lasts for almost a week, the condition is severe with severe symptoms of intoxication.

If the condition worsens, you should immediately contact the infectious disease specialist who visits the international clinic Medica24 without days off and holidays. Registration is carried out around the clock by phone +7 (495) 120-19-58. Early start of special therapy will avoid irreparable consequences.

How else can the infection proceed?

Atypical forms are more common in adults. So, when treating an adult with immunoglobulin in contact with a sick person, which is practiced with an unconditional probability of developing the disease, the symptoms of chickenpox are almost not expressed and this option is called erased.

In patients with severe chronic processes, tumors or after transplantation, on the contrary, severe forms develop according to the type of gangrene of the vesicles, with huge blisters – bullous, hemorrhagic with hemorrhages in the vesicles – with blood diseases. The generalized form flows very hard, when a rash forms even in the internal organs.

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When is the patient considered cured?

Not before he feels himself recovering, but according to medical criteria:

• The patient should not have a skin rash and the mucous membranes should also be clean.
• There are no signs of intoxication.
• At least three days the temperature should be normal.
• Blood test without abnormalities.

Most people get chickenpox in childhood; in adults, the infection is much more severe than in children, who, even during the heyday of the disease, feel well and are active.

The international clinic Medica24 uses the most effective domestic and foreign methods of therapy, which can significantly improve the quality of life of our patients and keep them active. Get help from a specialist of our medical center by calling +7 (495) 120-19-58

The reason for the development of chickenpox is a virus from a small family of herpes viruses, it was designated as type 3. On the one hand, it is very delicate and cannot withstand not only ultraviolet radiation, but simply sunlight.

Surfaces in the patient’s room are not required to be treated with antiseptics, because the ingress of the virus on them leads to his death, but in the cold it remains for a long time and is easily restored after freezing. At the same time, the viral particle is very volatile and flies from person to person on particles of saliva.

Who is resistant to virus infection?

Chickenpox is an amazingly sticky infection, and so most people get it during childhood. For some time, the newborn remains protected from the mother who had been ill with chickenpox a long time ago, the reason for this resistance is the antiviral antibodies inherited by the baby that circulated in the pregnant woman’s bloodstream. Once the antibodies are destroyed, the child will become defenseless.

Immunity after illness is characterized as stable, almost lifelong, however, in the rarest cases, re-disease is possible. The fact is that the viral particle settles in the nerve nodes – the ganglia, and even after a few years it can cause shingles or even repeated chickenpox, and the antibodies circulating in the blood do not cause trouble for the suddenly activated type 3 herpes virus.

Only a qualified infectious disease specialist is able to quickly make a differential diagnosis and identify the cause of the pathological condition. Sometimes it is necessary to resort to modern diagnostic methods. All this is possible in the international clinic Medica24.

Cause of infection: how is the disease transmitted from person to person?

It is unlikely that the cause of chickenpox can be the contact route of transmission – through touching the sick person. But a viral particle is perfectly transmitted by airborne droplets using an aerosol, which is formed in the air from the smallest droplets of saliva when a sick person coughs and talks.

Live infectious agents float in the smallest droplets of saliva, it is believed that the infection spreads through the ventilation system in the same way, because one patient is enough for a multi-apartment entrance, and all residents who do not have immunity will get sick.

In the event of a disease, you should immediately contact a specialist who sees you seven days a week and holidays at the international clinic Medica24. Early initiation of therapy will avoid irreparable consequences.

Why do spots and blisters form on the skin?

The main manifestation of chickenpox is a characteristic skin lesion. The chickenpox agent has a tropism for the skin; first of all, it rushes there, invades the cells and multiplies. While the particle is in the cell, the body reacts to the disorder by forming an inflammatory shaft: nearby vessels expand, through which immune cells actively arrive, filled with biologically active substances that dissolve all foreign substances. In general, inflammatory edema develops.

The spawning enemy agent and immune defenders together cause cell death. In place of the dead cell, a cavity is formed, which is filled with the surrounding inflammatory fluid, exfoliating the surface layer of the skin. So a bubble is formed from a speck.

When is the patient contagious to others?

The period from the penetration of an infectious agent to the development of symptoms of the disease in chickenpox lasts no more than 3 weeks. But already in the last few days of incubation in the body of an infected person, the virus multiplies and is released into the surrounding space. At this time, a person does not yet know about his illness, but he is already capable of infecting other people a day before the appearance of rashes.

For the duration of the appearance of new skin manifestations of chickenpox, a person is a source of infection. When new bubbles no longer appear, but there are still crusts, the person is no longer dangerous and may well come into contact with people. On average, the entire period of nucleation and maturation of blisters lasts about a week, but in adults weakened by concomitant diseases, the infection can proceed atypically, long and hard.

Specialists of the international clinic Medica24 always take into account not only the individual characteristics of the disease, but the possibilities and interests of each patient, so that the treatment is as comfortable as possible and really improves the quality of life. If you are not healthy, accidentally contacted a source of infection, or an infectious patient has appeared in the family, call: +7 (495) 120-19-58

Chickenpox is transmitted by the unusually volatile herpesvirus type 3. In the medical literature, a high probability of transmission of an infection is designated as 96% virulence, but in life it looks like this: if a sick chicken pox appears in the entrance of a house, then everyone who has not been ill before gets sick.

Is it always necessary to get tested for chickenpox?

Diagnosis is easy and often no testing is required to identify the causative agent. Chickenpox has very characteristic clinical manifestations, so the diagnosis is carried out by an infectious disease doctor based on symptoms.

The high degree of transmission also speaks in favor of infection, in most cases it is possible to trace where the infection came from. Diagnosis of the pathogen may be required in the atypical course of the disease, when the manifestations are either less or more pronounced and do not look like chicken pox.

What diagnostic methods can a doctor prescribe for chicken pox?

With any infectious process, changes are noted in the general blood test, and with chickenpox too, but there are no manifestations specific only to this disease. In most cases, there is an acceleration of the erythrocyte sedimentation rate – ESR.

To identify the pathogen, the contents of the vesicle or scraping-imprint from erosion are taken, after special silvering, microscopy determines accumulations of viruses or giant cells with many nuclei. With an atypical form, manifested by catarrhal changes in the throat, these reactions are also performed.

Molecular biological methods are used to detect antibodies to the virus in the blood, this is called a serological test. As a rule, diagnostics is performed in severe cases, however, the severity of changes does not correlate with the severity of the disease.

The infectious disease specialist of the international clinic Medica24, having an extensive clinical outlook, has at his disposal the most modern diagnostic methods and equipment with the ability to perform complex tests, which affects a favorable prognosis for the patient.

What illnesses can symptoms of chickenpox look like?

Differential diagnosis of chickenpox is carried out with other processes that also cause skin changes in combination with symptoms of intoxication. First of all, with SARS and herpes infections: generalized herpes and cytomegalovirus infection.

Looking for differences from pustular skin lesions – streptoderma and a dangerous infection of animals – foot and mouth disease, and other infections.

Only a qualified specialist with extensive diagnostic capabilities is able to quickly make a differential diagnosis and identify the cause of the pathological condition, and all this is possible in the infectious diseases center of the International Clinic Medica24.

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How to treat an infection?

In most cases, the treatment and prevention of chickenpox is symptomatic, that is, the symptoms of intoxication are removed, and in order to prevent infection of the vesicles, they are treated with antiseptics.

If someone in the family gets chickenpox: what are the preventive measures?

Most non-severe patients are treated at home.

• It is sufficient to isolate the patient in a separate room, where airing is carried out regularly.
• The family member caring for the patient must observe the usual hygiene rules. Of course, he must have immunity, that is, he had previously had chickenpox.
• Disinfect the room and objects used by the patient unnecessarily, as the virus is volatile but not viable outside the body.
• When all vesicles have crusted over, approximately 6 days after the last vesicle appears, the patient is no longer contagious.

What to do if there is no immunity to infection, but there was contact with the patient?

Lifelong immunity after illness. The quarantine period for chickenpox is 21 days, which is enough time for the virus to incubate.

In the first four days after contact with the patient, those who have not previously been ill and not vaccinated are vaccinated with the varicellose-zoster vaccine.