Viruses

SMALLPOX

Variola (the virus that causes smallpox) is the most notorious of the poxviruses. Smallpox was an important cause of illness and death in the developing world until recent times. In 1980, the World Health Organization (WHO) declared that smallpox had been completely wiped out. The last case was noted in Somalia in 1977.

Variola represents a significant threat as a biological warfare agent. Variola is highly infectious and is associated with a high death rate and secondary spread. Currently, the majority of the US population has no immunity, vaccine is in short supply, and no effective treatment exists for the disease. Two WHO-approved and inspected repositories remain: One is at the Centers for Disease Control and Prevention in the United States; the other at Vector Laboratories in Russia. It is widely believed that clandestine stockpiles exist in other countries such as Iraq and North Korea.

Variola virus is highly infectious when released into the air. It is environmentally stable and can retain its ability to infect people for long periods. Infection through contaminated objects such as clothing is infrequent. After a person is exposed to aerosolized virus, the virus multiplies in the person's respiratory tract. After a period of 7-17 days, variola is spread through the bloodstream to lymph nodes where it continues to multiply.

Variola then moves into smaller blood vessels near the surface of the skin where the inflammatory changes occur. The classic smallpox rash then begins. Two types of smallpox generally are recognized.

• Variola major, the most severe form, may cause death in up to 30% of unvaccinated people who develop it. (3% of people vaccinated people may also develop variola major).
  
  
• Variola minor, a milder form of smallpox, produces death in 1% of unvaccinated people.

Signs and symptoms

The symptoms of variola major occur after a 7- to 17-day incubation period. They begin acutely with high fever, headache, chills, aches, vomiting, abdominal and back pain. During the initial phase, 15% of people develop delirium (hallucinations), and 10% of light-skinned people may develop a fleeting rash.

After 2-3 days, the rash develops on the face, hands, and forearms and extends gradually to the trunk and lower part of the body. The sores progress all at once into fluid-filled sacs. The distribution of the rash is important in making the diagnosis of smallpox. A greater number of lesions will appear on the face arms and legs compared to the trunk. People with smallpox are most infectious on days 3-6 after the fever begins. Virus is spread to others through coughing and sneezing or by direct contact.

With the milder form of smallpox, variola minor, the skin sores are similar but smaller and fewer in number. People are not as ill as those who have variola major.

Diagnosis

Most doctors have never seen a case of smallpox and may have difficulty diagnosing it. Other viral illnesses with rash, such as chickenpox or allergic contact dermatitis, can look similar. Smallpox is different from chickenpox because of the distribution of the lesions and because they are all at the same stage of development everywhere on the body. With chickenpox, sores may be forming while others are scabbing over.

The failure to recognize mild cases of smallpox in people with partial immunity permits rapid person-to-person transmission. Exposed people may shed virus through coughing without ever showing the signs and symptoms of the disease.

The doctor may look at scrapings of tissue under a microscope but will be unable to tell the difference between smallpox and monkeypox or cowpox. Advanced PCR techniques have been developed and may provide for more accurate diagnosis in the near future.

Treatment

People with smallpox are usually isolated from people without smallpox for 17 days. Anyone exposed to either weaponized variola or people infected with smallpox must be vaccinated immediately; this may lessen or prevent the illness if done within 4 or 5 days of infection.

Treatment of smallpox is mainly to help relieve symptoms. The antiviral agent, cidofovir, may be effective in treating symptoms.

For more on smallpox, see Smallpox.

Prevention

Smallpox vaccine is used to prevent people from getting smallpox. The vaccine is given as a type of shot, but a 2-pronged needle is used to place the medication into the skin. This leaves a permanent scar, which many adults may still have from smallpox inoculations given to them when they were babies.

Once the shot is given, a small fluid-filled pimple usually appears 5-7 days later. A scab forms over the site during the next 1-2 weeks. Common side effects include low-grade fever and swollen lymph glands. People with weakened immune systems should not have the smallpox vaccination. This includes people with HIV, anyone with a history of eczema, and pregnant women.

MONKEYPOX

The monkeypox virus is a naturally occurring relative of variola, which is found in Africa. The first case of human monkeypox was identified in 1970, but fewer than 400 cases have been diagnosed since. Some concern exists that monkeypox may be weaponized, however, human monkeypox is not as potent as smallpox. Pneumonia due to monkeypox may cause death in about half of people who develop it.

VIRAL ENCEPHALITIDES

The viral encephalitides, Venezuelan equine encephalitis (VEE) virus, western equine encephalitis (WEE) virus, and eastern equine encephalitis (EEE) virus, are members of the Alphavirus genus and are regularly associated with encephalitis. These viruses were recovered from horses during the 1930s. VEE was isolated in the Guajira peninsula of Venezuela in 1930, WEE in the San Joaquin Valley of California in 1930, and EEE in Virginia and New Jersey in 1933.

Although natural infections with these viruses occur following bites from mosquitos, the viruses are also highly infectious when spread through the air. If intentionally released as a small particle aerosol, this virus may be expected to infect a high percentage of people exposed within a few miles.

VEE virus has the capacity to produce epidemics. Outcomes are significantly worse for the very young and the very old. Up to 35% of people infected may die. WEE and EEE typically produce less severe and widespread disease but are associated with death rates as high as 50-75% in those with severe illness.

Signs and symptoms

• VEE: After an incubation period of 2-6 days, people with VEE develop fevers, chills, headache, aches, sore throat, and sensitivity to light (eyes). They may become mildly confused, have seizures or paralysis, or go into a coma. For those who survive, their nervous system functions usually recover completely.
  
  
• EEE: The incubation period for EEE varies from 5-15 days. Adults may have certain early symptoms up to 11 days before the onset of nervous system problems such as mild confusion, seizures, and paralysis. Signs and symptoms include fever, chills, vomiting, muscle rigidity, lethargy, slight paralysis, excess salivation, and difficulty breathing. Children frequently develop swelling on their face and near their eyes. Up to 30% of survivors of severe disease have permanent nervous system problems such as seizures and various degrees of confusion (dementia).
  
  
• WEE: The incubation period is 5-10 days. Most people have no symptoms, or they might develop a fever. Other symptoms include nausea, vomiting, headache, a stiff neck, and drowsiness. Up to 90% of victims younger than 1 year have seizures. Typically, adults recover completely. Children, especially newborns, may have lasting nervous system problems.

Diagnosis

Laboratory tests, including nasal swab samples, may show any of the 3 viruses.

Treatment

No specific treatment is available. Doctors will help control symptoms. For some people that may include medications to control fever and seizures or help breathing.

Prevention

A vaccine for VEE can be given as an injection for those at high risk, such as laboratory field personnel. About 20% of those who receive the vaccine fail to respond to it, meaning they would not be protected by the vaccine. An additional 25% of those vaccinated develop high fever, chills, and feel sick enough to be in bed.

A different vaccine was developed for those who did not develop protection from the initial activated vaccine. It is an inactivated vaccine, which produces only mild tenderness at the injection site. Shots are given at 2- and 4-week intervals until the person responds and develops antibodies as protection.

The EEE vaccine is inactivated and given as an injection (1 to start and another 28 days later). There are no serious side effects or long-term problems with this vaccine. Boosters are required.

VIRAL HEMORRHAGIC FEVERS

Viral hemorrhagic fevers are caused by 4 families of viruses.

• Arenaviridae (Lassa, Argentine, Bolivian, Brazilian, Venezuelan hemorrhagic fevers)
  
  
• Bunyaviridae (Rift Valley, Crimean-Congo, Hantaan)
  
  
• Filoviridae (Marburg, Ebola)
  
  
• Flaviviridae (Yellow, Dengue, Kyasanur Forest, Omsk HFs)

The best known of the viral hemorrhagic fevers is Ebola virus. First recognized in Zaire in 1976, the virus has been linked to 3 outbreaks in Africa. Up to 92% of people who contract Ebola will die. A related virus was discovered in Reston, Virginia, in 1989 in association with an outbreak of illness among monkeys imported from the Philippines. No human cases occurred with this outbreak.

These viruses are each characterized by an acute generalized illness that includes feeling quite ill (flulike illness) with profound exhaustion and often associated internal bleeding. All agents are highly infectious via the aerosol route, and most are stable as respiratory aerosols. Thus, they possess characteristics that may make them attractive for use by terrorists.

The agents that produce viral hemorrhagic fever are all simple RNA viruses. They are able to survive in blood for long periods, which means they can infect people who are around animals slaughtered domestically. These viruses are linked to the rodent or insect that helps to spread them, which helps in searching for a diagnosis.

The specific viral hemorrhagic fever that develops depends on many factors such as the strength of the virus, its strain, and the route of exposure.

Signs and symptoms

All viral hemorrhagic fevers primarily target blood vessels. They damage the blood vessels and produce internal bleeding. Victims may have fever, aches, exhaustion, infected eyes, low blood pressure to severe shock, and bleeding in tiny blood vessels such as in the eye. More severe cases will have serious problems with the nervous system, liver, and lungs.

Depending on the type of virus, symptoms can include deafness, severe internal bleeding, kidney failure, rash, black (bloody) vomit, and other life-threatening symptoms.

Diagnosis

It is important for the doctor to know a person's travel history in making a diagnosis of viral hemorrhagic fever. These agents are linked tightly with their natural geographic area and the ecology of the species and vectors found in that specific locale. Victims often recall exposures to rodents (Arenavirus, Hantavirus), mosquitoes (Rift Valley fever virus, yellow and dengue fever viruses), or even slaughtered horses (Rift Valley fever virus, Crimean-Congo virus).

Laboratory tests may be helpful. Testing can be conducted at the CDC in Atlanta or the US Army Medical Research Institute of Infectious Disease (USAMRIID) at Fort Detrick in Frederick, Maryland.

Treatment

Treatment for viral hemorrhagic fevers is largely directed at easing the discomfort of the symptoms. Victims benefit from being placed in a hospital setting immediately. Air transport is not advised. Sedative and pain-relieving medications are helpful, but aspirin and similar drugs should not be given because of their tendency to make bleeding worse.

Doctors will also not usually use IV lines or catheters because of bleeding problems. The treatment for bleeding is controversial. Generally, mild bleeding is not usually treated, but severe bleeding requires appropriate replacement therapy (blood through an IV line).

Specific treatment with ribavirin has been used and is currently under investigation as a therapy for Lassa fever, Hantavirus, Crimean-Congo, and Rift Valley Fever. Treatment is most effective if begun within 7 days. Ribavirin has poor activity against the filoviruses and flaviviruses.

Prevention

The only established and licensed virus-specific vaccine against any of these viruses is the yellow fever vaccine. It is mandatory for those traveling into areas of Africa and South America where the disease is commonly found. Current trials are underway for further vaccines and antibody therapies.