Chapter 4
Treatment and Living with West Nile Virus

One reason that health experts emphasize prevention of West Nile virus is that at West Nile meningitis, present time there is no specific treatment for the illness. That is, there are no known medications or therapies that can eradicate the virus. Antibiotics, used to treat bacterial infections, are ineffective against viruses. Several patients hospitalized with West Nile virus–related fever, chills, body aches, encephalitis, or meningitis have been given antibiotics before doctors knew they had West Nile virus, and these medications did not help the patients' conditions. Doctors have also tried using ribavirin and interferon on patients severely ill with West Nile virus infection. Ribavirin is an antiviral medication that kills West Nile virus in a laboratory test tube and is effective against several other flaviviruses in humans. Interferon is a natural immune-system chemical that can be used to strengthen the immune response to an invading pathogen. However, these medications did not help the patients, and in some instances, they made conditions worse.

Although ribavirin and interferon did not help the West Nile patients to whom they were given, the National Institute of Allergy and Infectious Diseases, which is sponsoring much research aimed at conquering West Nile virus, says that "[These] drugs may be effective against West Nile virus because the infection is typically not chronic and antiviral drugs have been identified to be effective in vitro [in a laboratory test tube] against other flaviviruses."¹⁵ Therefore, experts emphasize that controlled scientific studies and clinical trials on antiviral agents are needed before any conclusions can be reached on whether or not they may be useful in treating West Nile virus. Such studies are also under way on entirely new drugs that might be useful in the battle against the virus.

Clinical Trials and Controlled Studies

Investigations on new drugs to treat West Nile virus begin in a laboratory, where researchers initially test these substances in a test tube or a culture dish to see if they are effective in killing a pathogen. Then compounds that show promise are tested on laboratory animals for safety and effectiveness.

Ribavirin, Interferon,
and West Nile Virus

The antiviral drug ribavirin has not yet been proven effective or ineffective against West Nile virus in people. But in a laboratory test tube, high doses of the drug resulted in reduced levels of the genetic material of the virus in infected cells. The drug also decreased cell damage due to West Nile virus infection.

Ribavirin has been used to successfully treat yellow fever and Japanese encephalitis, two diseases caused by flaviviruses related to West Nile virus. For this reason, researchers are hopeful that it will also prove to be effective against West Nile virus when tested in actual patients. It can have serious side effects, such as causing a condition called anemia, so its use must be carefully monitored.

Ribavirin is sometimes used in combination with interferon, a man-made version of one of the body's natural defenses against viruses and other pathogens. In other cases, the two drugs are administered separately. By itself, interferon has been shown to significantly reduce brain inflammation and damage from Saint Louis encephalitis virus in people. Researchers believe it may be useful in combating West Nile virus either separately or in combination with ribavirin. Like ribavirin, though, interferon can have serious side effects, including flulike symptoms and a decrease in infection-fighting blood cells, so it too must be administered very carefully.

Sometimes such laboratory tests are performed on existing drugs, such as ribavirin and interferon, that have proven to be effective against other diseases. These medications have already been marketed for use with other diseases, but before they are approved to treat West Nile virus, they must prove effective against West Nile virus in a test tube.

Once a drug passes these laboratory and animal tests, the researcher can apply to the federal Food and Drug Administration (FDA) to begin clinical trials on humans. These trials are generally sponsored by a research institution such as the National Institutes of Health or by a pharmaceutical company. They are set up at numerous hospitals and clinics throughout the nation. Patients can find out about and enroll in clinical trials through their physicians or through sponsoring agencies. All participation is voluntary with the understanding that the experimental drug may or may not help.

Rules and regulations governing clinical trials are developed and enforced by the FDA in the United States and by comparable organizations in other countries. Each clinical trial generally proceeds through three mandatory phases before a drug can be approved for marketing and widespread use.

Some Drugs That May Be Effective Against West Nile Virus

Dr. John Morrey and his colleagues at the Utah State University Institute for Antiviral Research have tested many chemical compounds against West Nile virus in the laboratory. Recently they identified six drugs that were effective against the virus in laboratory cultures. The drugs included 6-azauridine, 6-azauridine triacetate, cyclopentenylcytosine, mycophenolic acid, 2-thio-6-azauridine, and pyrazofurin. Each acts in some manner to interfere with the workings of viral cells and therefore renders the virus incapable of causing disease. The researchers indicated that further laboratory testing is needed before any of the drugs can be evaluated as possible treatments in people and animals.

In the preliminary, or Phase 1, studies, a small group of patients, usually no more than twenty, receives the new drug to determine safe and effective doses and to check for adverse effects. In Phase 2, also known as the pilot phase, a larger group of patients, perhaps as many as one hundred, are given the drug. If the medication does not appear to be beneficial, the clinical trial may be halted and the drug rejected or sent back to the laboratory for improvement. If, on the other hand, the drug gives dramatic results and has few or no adverse effects, the FDA may assign it a so-called fast-track status, where some of the lengthy testing requirements are waived so the drug becomes available sooner to people who need it.

In Phase 3, or the control phase, hundreds or even thousands of patients are enrolled and randomly assigned to either an experimental or a control group. People in the experimental group receive the new drug, but those in the control group are given a placebo, an inactive substance that appears to be authentic. Results from the control group indicate to statisticians whether any positive effects in the study are due to patients' expectation of success rather than to the medicine itself. Patients are not informed which group they are in.

Once Phase 3 is completed in a satisfactory manner, the FDA may approve the new treatment for marketing. Sometimes further studies known as Phase 4 postmarket studies are conducted to learn more about long-term effects or to recheck any questionable data from earlier trials.

Patients who are severely ill with West Nile virus need treatment immediately, so sometimes all these lengthy new-drug testing requirements seem to prevent those who need a drug from receiving it except on an experimental basis. However, the FDA requires such rigorous testing before approving a drug because many new compounds end up causing adverse effects.

Drugs Under Investigation

In addition to beginning controlled clinical studies on existing antiviral drugs against West Nile virus, researchers are experimenting with entirely new chemical compounds to treat the virus. Dr. John Morrey of Utah State University Institute for Antiviral Research in Logan, for example, has developed a technique of screening large numbers of chemical compounds that might be effective. Morrey has already tested hundreds of substances in hopes of finding one that will do well against West Nile virus.

Another area of drug-related research is looking at chemicals that might be able to compensate for a missing protein discovered by investigators at the Pasteur Institute in Paris, France. These researchers have been studying a protein found in some mice that prevents the virus from reproducing inside the brain. In this research, scientists genetically alter a mouse's brain to block this protein, enabling the virus to replicate. A mouse whose protein is blocked tends to die quickly from West Nile virus. Although no one knows whether or not the protein is normally present in humans, experts believe that further knowledge about it could lead to important new treatments. "The most promising thing about this [Pasteur Institute] study is that it could help lead to a drug that would restore the missing protein and give patients protections against replications of the virus,"¹⁶ said Catherine A. Laughlin of the National Institute of Allergy and Infectious Diseases.

Supportive Therapy

Until investigators are able to test and find drugs effective against West Nile virus, the only treatment available is known as supportive therapy. This involves doing what is necessary to control symptoms and make the patient as comfortable as possible, much like influenza or colds are treated. If the person has fever and aches and pains, for example, medications like acetaminophen, which lowers fever and reduces pain, are administered. Patients are advised to drink plenty of fluids and to rest in bed until the body's own immune system can fight off the infection so recovery can begin.

For people who experience more severe illness from West Nile virus infection, supportive therapy may involve more drastic measures such as being hospitalized and receiving intravenous fluid and medications, assistance with breathing, and drugs necessary to prevent secondary infections like pneumonia from starting.

Patients hospitalized with encephalitis, meningitis, or meningoencephalitis often require extensive supportive therapy that includes medications to reduce swelling in the brain, drugs to diminish seizures, sedatives to treat restlessness or agitation, and pain and fever relievers like acetaminophen. Doctors give such patients intravenous fluids to keep them hydrated and to help flush out the infection. They are also given as much nutrition as they are able to consume or, if unable to eat, are fed through a feeding tube inserted into the stomach.

If encephalitis causes confusion or disorientation, psychiatric care and medications may be needed to treat these symptoms. If paralysis is present, the patient may need physical therapy, occupational therapy, and speech therapy after recovery from the acute phase of the illness. This acute phase can last anywhere from a few weeks to several months. Physical therapy is performed by a licensed physical therapist and involves exercises and stimulation to help retrain muscles that were paralyzed or extremely weakened. Some patients must learn to walk again or to use other muscle groups that were temporarily out of commission. Occupational therapists help people relearn how to perform everyday tasks such as eating, dressing themselves, or bathing that they may have lost the ability to do while extremely ill. Speech therapists may be needed to help a person learn to speak again after being paralyzed if the muscles or brain centers used in speech are affected.

Some patients who develop severe complications from West Nile virus may require even more extensive supportive therapy. One sixty-nine-year-old New York man, for example, was hospitalized with fatigue; poor concentration; and weakness, numbness, and tingling in his arms and legs. This progressed to the point at which he was no longer able to walk. Doctors diagnosed him with Guillain-Barré syndrome, which his physicians believed was triggered by a West Nile virus infection.

The patient was placed in the intensive care unit of the hospital where he was admitted. Soon his weakness increased, and he became unable to breathe. He was placed on a mechanical ventilator and given plasmapheresis treatments. Plasmapheresis is a common method of treating Guillain-Barré syndrome. It consists of replacing the plasma—the liquid portion of blood—intravenously using a sophisticated filtering machine. The goal of this procedure is to free the body of any impurities in the plasma that are causing the Guillain-Barré condition. In this man's case, the plasmapheresis did not seem to help. Doctors administered intravenous gamma globulin, an immune protein, to try to bolster his immune system to fight the infection. This did not seem to help either. The patient developed pneumonia in his lungs, which required treatment with antibiotics. Then he developed blood clots in his legs, so doctors administered blood-thinning medications. After ten weeks in the intensive care unit, his condition stabilized to the point that he was able to be transferred to a nursing home, where he continued to be fed through a stomach tube until he could eat on his own. Although he was gravely ill, this patient did recover and was eventually able to go home.

Recovering from West Nile Virus Infection

Many patients who are severely ill from West Nile virus do not recover and eventually die from the illness. Others get better but suffer permanent impairments of muscle control, memory, speech, vision, hearing, or sensation that must be dealt with for the rest of their lives. Older adults in particular are likelier to die from the disease, but some experts say that those who survive have a good chance of not having lasting disabilities. "In older adults, West Nile virus carries a high death rate—about one in five people—but the outcome is favorable for the survivors,"¹⁷says Dr. Yitsal N. Berner, a lead researcher in a recent study in Israel. The investigators in this study discovered that 88 percent of the older adult survivors returned to their previous level of functioning after their recovery.

However, another recent study in New York found that 67 percent of the people hospitalized with West Nile virus still reported aftereffects like fatigue as much as one year after leaving the hospital. Fifty percent had ongoing memory loss, 49 percent had difficulty walking, 44 percent had muscle weakness, and 38 percent were depressed after the same length of time. The patients in this study had been hospitalized for two to forty-seven days due to West Nile virus encephalitis, meningitis, or meningoencephalitis. Some were able to go home after being released from the hospital, but some had to be put in long-term care facilities. Even among those patients who were able to go home, several required physical therapy, occupational therapy, and speech therapy.

The differences in findings between the study in Israel and the one in New York may be due to the fact that, in general, people in areas where West Nile virus has been around for a long time do not experience as severe a degree of illness as do those where the virus is newly arrived. This may, in turn, explain why the affected people in Israel, where the virus has been present for many years, did not seem to have as many difficulties living with the aftermath of West Nile virus. In New York, more serious illness in the majority of the patients could then translate into less-complete recoveries.

Recovery and Previous Illness

Another factor that can influence how much effect West Nile virus has on a person's ability to recover and function is the presence of previous illness. Joan, for example, was weakened both by cancer and by cancer treatment when she was bitten by a mosquito and developed West Nile virus. She initially experienced a fever and mental confusion, which progressed to a comatose state. The fifty-five-year-old woman was hospitalized in an intensive care unit, diagnosed with encephalitis, and placed on a ventilator. For more than two months she was unable to talk, move, breathe, or eat, even after emerging from her coma. Finally, after doctors inserted a breathing tube in her neck, she was able to breathe without a ventilator. At a rehabilitation center, she began her recovery, which doctors said would include speech therapy, physical therapy, and occupational therapy. Whether she will ever recover fully is unknown, though chances are that she will experience permanent disability. "Many of these patients who get these serious encephalitis symptoms don't return to their baseline state and many have severe long-term complications,"¹⁸says Dr. Lyle Petersen, a Centers for Disease Control expert on West Nile virus, in comments about the woman's condition. This is especially true when the patient had a previous illness that weakened him or her before the West Nile virus struck.

Because West Nile virus is still so new in the United States, doctors in this country acknowledge that they lack the firsthand experience to make reliable predictions on whether or not patients will recover fully from the effects of a serious case of the disease. It will take some time to fully assess the long-term effects and the issues that patients affected by these complications will face in living with the aftermath of a West Nile virus infection. Until more studies on West Nile virus patients are completed, experts rely primarily on reports from elsewhere in the world and on knowledge of how people with serious cases of encephalitis or meningitis caused by other infections respond.