Mononucleosis
Mononucleosis
Disease History, Characteristics, and Transmission
Introduction
Mononucleosis is a self-limiting viral disease caused by the Epstein-Barr virus (EBV). EBV is considered to be one of the most common viruses among humans and most people become infected with the virus at some point during their lives. When infection with EBV occurs during adolescence or young adulthood, the infection develops into mononucleosis 35–50% of the time. The disease occurs worldwide.
EBV infection during early childhood is usually asymptomatic. When an adolescent or young adult develops mononucleosis the symptoms include fever, sore throat, swollen glands, swollen lymph nodes, and general fatigue. In severe cases, patients may display symptoms for months, but usually they will resolve within four weeks of initial infection. There is no vaccine to prevent mononucleosis and treatment of symptoms relies largely on rest and rehydration.
No areas have been identified as having an increased risk of infection and most cases occur sporadically with no reports of outbreaks. The long incubation period of infection coupled with the universal presence of the viral agent makes epidemiological control impractical.
Disease History, Characteristics, and Transmission
Mononucleosis is also known as Pfeiffer's disease, Filatov's disease, the kissing disease, glandular fever, or, simply, mono. The disease was first termed glandular fever by a group of German physicians in the 1880s due to the obvious swelling of the lymph nodes and glands. In 1920, scientists discovered that the infection was associated with white blood cells called mononuclear leukocytes, and thus it was also called infectious mononucleosis. The causative agent wasn't identified as EBV until 1968, when Michael Epstein (1921–) and Yvonne Barr (1932–) discovered the virus.
EBV is a member of the family of human herpes viruses. It is one of the most common human viruses and is responsible for 90% of mononucleosis cases. Cytomegalovirus is another member of this family of viruses and may cause mononucleosis in a small number of cases. EBV causes mononucleosis by infecting lymphocytes, or white blood cells, which subsequently reduces host immunity for the period of infection. EBV has also been implicated in more severe diseases, such as post-transplant lymphoproliferative disease, Hodgkin's disease, nasopharyngeal carcinoma, and Burkitt's lymphoma.
Mononucleosis has an incubation period of 4–7 weeks, during which symptoms may not be present. Most children are exposed to EBV at a young age, which generally results in a mild, asymptomatic infection. If initial infection occurs during adolescence or young adulthood, symptoms may present as a persistent cold or flu and may include fever, enlarged lymph nodes on the neck, sore throat, muscle aches, fatigue, and white patches on the tonsils. Enlargement of the spleen occurs in 25–75% of cases and poses threat of further complications due to the possibility of rupture. Other symptoms may include abdominal pain, headache, jaundice, depression, weakness, skin rash, and swollen liver. The broad spectrum of possible symptoms means that almost all cases of mononucleosis are unique to each patient.
Generally the infection is self-limiting within 2–4 weeks, but in some cases the course of disease is considered chronic and patients may suffer from symptoms for months, or even years. In most cases, hospitalization is seldom required unless complications, such as ruptured spleen or liver problems, arise. There have been no indicating factors to suggest why some people develop more serious symptoms than others, however it is postulated that external stressors in a patient's life could potentially play a key role. The EBV infection does not necessarily affect only people with compromised immunity and quite often, those that contract mononucleosis appear fit and healthy.
Mononucleosis is considered relatively contagious and is transmitted through contact with saliva or mucus, which can occur by kissing or by the sharing of drinks and utensils. In some instances, transmission has been linked to blood and may occur through transfusion. Infected people may be contagious while symptomatic but even asymptomatic persons can carry and spread the virus for life, and, as such, remain a primary reservoir for transmission.
Scope and Distribution
EBV is found worldwide. Mononucleosis most frequently occurs in young adults between 15 and 17 years of age, but it potentially affects people of all ages. One to three percent of college students are affected annually.
Generally, most people will contract EBV at some stage of their life and in the United States, 95% of 35 to 40 year-olds have previously been infected. In most cases, previous infection will have occurred without recognition or diagnosis. This is due to the fact that during early childhood, infection is mild, usually producing no symptoms, or only mild symptoms similar to the common cold.
The statistics are much the same for developing nations, where 90% of children contract asymptomatic EBV when under five years old. These individuals are then not susceptible to mononucleosis caused by EBV. It is interesting to note that mononucleosis is a disease that more commonly affects people in developed countries than those in developing countries. Variations in social etiquette and acceptable social behaviors may account for such differences, since mononucleosis is a disease that requires direct contact with saliva for transmission, such as through intimate kissing. Another theory accounting for this difference is that in developing countries, individuals are likely to be exposed to EBV while young, and so would develop a mild form of the infection. In developed countries, individuals may be protected from the virus until adolescence. Without the immunity conferred by prior infection, mononucleosis would develop.
There does not appear to be a strong link between the health status of a person and the extent to which they will develop mononucleosis, but potentially people who have a compromised immune systems may be at higher risk of developing mononucleosis when infected with EBV.
The global scope of EBV almost certainly ensures the continued transmission of the disease. Most cases of mononucleosis occur sporadically and outbreaks are rare. In most cases, people presenting symptoms of the disease have no recollection of possible exposure to the virus, and it is uncommon that infection would be transmitted to a group from a single source. In any large adult group environment, over 90% of the people will probably have been exposed to the EBV previously and, in such situations, an outbreak is unlikely.
There are no known ethnic, racial, or sexual factors that predispose a person to develop mononucleosis. However, it is interesting to note that, in developed countries, infection more often occurs in persons belonging to a higher socioeconomic class. This may be attributed to differences in lifestyle and increased opportunities for the social interactions associated with this disease. In addition, the fact that these individuals receive a higher level of protection from childhood infections may also play a role. The only gender-related factor associated with mononucleosis is that 90% of cases of ruptured spleens occur in males.
Treatment and Prevention
Diagnosis of mononucleosis may be confirmed through serological testing to determine the presence of abnormal white blood cells. The “mono spot” test is a specific test designed to detect the presence of antibodies that have developed as a result of the viral infection. These are known as heterophile antibodies and usually develop about one week after onset of the disease. They peak during the first month of illness, but may persist in the blood for several months and up to one year. Some people infected with mononucleosis may never develop these antibodies and so the test may return a false negative result. Generally, the testing is accurate with false positive results occurring in only a small number of patients.
There is no vaccine or preventative medicine available for mononucleosis, largely due to the fact that it results from a viral infection. However, the severity of other infections related to EBV, in addition to a further understanding of the virus, has prompted scientists to investigate avenues for creating a potential vaccine. It is likely that the vaccine would be targeted towards minimizing the clinical manifestations of primary infection with EBV, rather than towards malignancies associated with the disease.
The fact that EBV infection in early childhood seldom results in development of mononucleosis, while primary infection occurring after adolescence develops into the disease in 35–50% of cases has encouraged researchers. This observation suggests that a vaccine generating a minimized immune response may potentially limit the clinical symptoms of mononucleosis. The limiting factor in this area of research is that such a vaccine requires the use of an attenuated (weakened) virus, which has been deemed unsafe for administration to healthy adolescents. For this reason, it is unlikely that the vaccine would meet strict licensing laws.
In most cases, mononucleosis resolves within four weeks after symptoms first arise, during which time treatments are targeted at the symptoms of the infection. Rest is one of the key elements to recuperation and maintenance of fluid intake is essential. Patients are also advised to avoid heavy activity for at least one month following initial infection to reduce the risk of spleen rupture. Nonsteroidal anti-inflammatory (NSAID) medication may be used to treat pain and reduce fever and swelling, and dietary supplements may help boost the immune system. Antibiotics may be useful in treating throat infections often accompanying mononucleosis, but will not be effective against EBV. It is not recommended that patients use aspirin due to the possibility of developing Reye's syndrome, a potentially fatal disease.
The typically benign and self-limiting course of mononucleosis, in addition to the ubiquitous nature of the virus, makes prevention virtually impossible. With over 90% of the western adult population returning positive tests for previous infection, person-to-person infection remains highly likely in societies worldwide.
Prevention of the disease may not be beneficial. As noted, childhood infection with EBV typically results in few or no symptoms. In contrast, infection during adolescence tends to result in a more serious disease. This suggests that intentional early primary exposure could potentially be used as a method of preventing the later onset of mononucleosis.
Impacts and Issues
The statistics show that inevitably, at some stage of their life, almost the entire world population will be exposed to, contract, and harbor the Epstein-Barr virus. However, the majority of people who encounter infection during early childhood will not even develop mononucleosis. It is the omnipresence of EBV that prevents the eradication of the infection.
WORDS TO KNOW
ANTIBODY: Antibodies, or Y-shaped immunoglobulins, are proteins found in the blood that help to fight against foreign substances called antigens. Antigens, which are usually proteins or polysaccharides, stimulate the immune system to produce antibodies. The antibodies inactivate the antigen and help to remove it from the body. While antigens can be the source of infections from pathogenic bacteria and viruses, organic molecules detrimental to the body from internal or environmental sources also act as antigens. Genetic engineering and the use of various mutational mechanisms allow the construction of a vast array of anti-bodies (each with a unique genetic sequence).
CHRONIC FATIGUE SYNDROME: Chronic fatigue syndrome (CFS) is a condition that causes extreme tiredness. People with CFS have debilitating fatigue that lasts for six months or longer. They also have many other symptoms. Some of these symptoms are pain in the joints and muscles, headache, and sore throat. CFS appears to result from a combination of factors.
EPSTEIN BARR VIRUS (EBV): Epstein-Barr virus (EBV) is part of the family of human herpes viruses. Infectious mononucleosis (IM) is the most common disease manifestation of this virus, which once established in the host, can never be completely eradicated. Very little can be done to treat EBV; most methods can only alleviate resultant symptoms.
MONO SPOT TEST: The mononucleosis (mono) spot test is a blood test used to check for infection with the Epstein-Barr virus, which causes mononucleosis.
MONONUCLEAR LEUKOCYTE: A mononuclear leukocyte is a type of white blood cell active in the immune system.
The impact of mononucleosis may be seen on a personal level. Severe cases may keep patients in bed and away from their normal activities for many weeks or even months. This is a particular problem for students, since they may miss classes during this time. In addition, being removed from social groups for extended periods may generate emotional issues among adolescents. This is especially significant considering that the disease commonly occurs at an important time in social development.
In addition, social pressures can occur when adults contract mononucleosis. Adults may lose income due to an inability to work, which may put economic pressures on families and further strain family relationships. Such concerns may lead individuals to shorten their recovery period and return to their regular activities earlier than recommended. In these cases, symptoms of fatigue may persist for longer than usual and result in lower productivity.
In some chronic cases of the disease, patients suffer symptoms for more than six months and sometimes for years. In many chronic cases, it is considered that the mononucleosis contributed to the development of chronic fatigue syndrome (CFS). Although the exact causes of CFS have not been identified, approximately 10% of mononucleosis patients will go on to suffer from it and so CFS is considered a possible side effect of the disease. In these situations, people are unable to work, study, or socialize for long periods of time and, sometimes, permanently.
Cases of mononucleosis are generally much more severe in people with compromised immunity, and the complications that develop from such infections may prove fatal. Immunocompromised individuals include those who have undergone organ or marrow transplants, individuals receiving chemotherapy, and those with autoimmune diseases. The development of an immune disorder later in life may also result in a severe relapse of mononucleosis infection among people who previously only carried the virus in a latent form. While fatalities resulting from mononucleosis were previously a rare occurrence, the growing numbers of people suffering from immune disorders makes this a potentially significant threat in the future.
Bone marrow has been identified as one site of latent EBV persistence within the body. It has also been observed that an EBV-positive individual who receives a bone marrow transplant from an EBV-negative donor is found to be EBV-negative following transplantation. This means that this recipient is again susceptible to infection and most likely, if the transplant occurs during adulthood, will develop mononucleosis. This raises a new concern—the loss of immunity to certain diseases following transplantation. This could become a more serious problem as organ transplantation becomes a more common procedure.
Primary Source Connection
A diagnosis of mononucleosis can mean a period of convalescence for about two months, and that is usually a difficult order for an otherwise healthy teenager or young adult, who are the prime ages for infection with the viruses that cause mono. In the following article from the FDA Consumer, author Judith Levine Willis discusses mono and it's implications for physical and social limitations for young people. At the time the article was published in 1998, Judith Levine Willis was on the public affairs staff of the Food and Drug Administration. She has since authored, as Judith Levine, books about gender, health, and consumer issues.
Mono: Tough for Teens and Twenty-Somethings
Missed parties. Postponed exams. Sitting out a season of team sports. And loneliness. These are a few of the ways that scourge of high school and college students known as “mono” can affect your life.
The disease whose medical name is infectious mononucleosis is most common in people 10 to 35 years old, with its peak incidence in those 15 to 17 years old. Only 50 people out of 100,000 in the general population get mono, but it strikes as many as 2 out of 1,000 teens and twenty-somethings, especially those in high school, college, and the military. While mono is not usually considered a serious illness, it may have serious complications. Without a doubt your lifestyle will change for a few months.
You've probably heard people call mono the “kissing disease.” But if your social life is in a slump, you may wonder, “How did I get this ‘kissing disease’ when I haven't kissed anyone romantically recently?”
Here's how. Mono is usually transmitted though saliva and mucus—which is where the “kissing disease” nickname comes from. But the kissing or close contact that transmits the disease doesn't happen right before you get sick. The virus that causes mono has a long incubation period: 30 to 50 days from the time you're exposed to it to the time you get sick. In addition, the virus can be transmitted in other ways, such as sipping from the same straw or glass as an infected person—or even being close when the person coughs or sneezes. Also, some people can have the virus in their systems without ever having symptoms and you can still catch it from them.
Two viruses can cause mono: Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Both viruses are in the herpes family, whose other members include viruses responsible for cold sores and chickenpox.
EBV causes 85 percent of mono cases. About half of all children are infected with EBV before they're 5, but at that young age, it usually doesn't cause any symptoms. If you don't become infected with EBV until you're a teen or older, you're more likely to develop mono symptoms. After you're infected, the virus stays with you for life, but usually doesn't cause any additional symptoms. Still, every now and then you may produce viral particles in your saliva that can transmit the virus to other people, even though you feel perfectly fine. By age 40, 85 to 90 percent of Americans have EBV antibodies, indicating they have the virus in their systems and are immune to further EBV infection.
CMV is also a very common virus. About 85 percent of the U.S. population is infected with it by the time they reach adulthood. As with EBV, CMV is frequently symptomless, and mono most often results when infection occurs in the teens and 20s. Sore throat is less common in people who have CMV mono than in those infected with EBV.
As another one of its nicknames—glandular fever— implies, perhaps the most distinguishing mono symptom is enlarged glands or lymph nodes, especially in the neck, but also in the armpit and groin.
Another common mono symptom is fever. A temperature as high as 39.5 degrees Celsius (103 degrees Fahrenheit) is not uncommon. Other symptoms include a tired achy feeling, appetite loss, white patches on the back of the throat, and tonsillitis.
“My tonsils got so swollen they were touching each other in back,” says Heidi Palombo of Annandale, Va., who had mono when she was a senior in college. She recalls her throat being “so hot and swollen that the only thing that felt good was ice water.”
Cold drinks and frozen desserts are both ways to relieve sore throat symptoms. Doctors also recommend gargling with saltwater (about half a teaspoon salt to 8 ounces of warm water) and sucking on throat lozenges available over the counter in pharmacies and other stores. If throat or tonsils are infected, a throat culture should be taken so the doctor can prescribe an appropriate antibiotic. Ampicillin is usually not recommended because it sometimes causes a rash that can be confused with the pink, measleslike rash that 1 out of 5 mono patients develops.
For fever and achiness, you can take acetaminophen (marketed as Tylenol, Datril and others) or ibuprofen (marketed as Advil, Motrin, Nuprin, and others). If you're under 20, don't take aspirin unless your doctor approves it. In children and teens, aspirin taken for viral illnesses has been associated with the potentially fatal disease Reye syndrome. Sometimes a person with mono may have trouble breathing because of swelling in the throat, and doctors have to use other medications and treatment. A person who has mono—or those caring for the person—should contact a doctor immediately if the person starts having breathing problems.
Some people with mono become overly sensitive to light and about half develop enlargement of the spleen, usually two to three weeks after they first become sick. Mild enlargement of the liver may also occur.
Whether or not the spleen is enlarged, people who have mono should not lift heavy objects or exercise vigorously—including participating in contact sports—for two months after they get sick, because these activities increase the risk of rupturing the spleen, which can be life-threatening. If you have mono and get a severe sharp, sudden pain on the left side of your upper abdomen, go to an emergency room or call 911 immediately.
Because its symptoms can be very similar to those of other illnesses, doctors often recommend tests to find out exactly what the problem is.
“I was misdiagnosed at first and told I was bit by a spider,” writes John L. Gipson, of Kansas City, Mo., in a note he posted to a Website. “That's what I thought because I had killed a spider in my room. I figured I'd been bitten by a spider in my sleep. A few days after. I had no energy, a fever. and those pea-sized bumps on the back of my neck.” Gipson returned to his doctor, who did blood tests and diagnosed mononucleosis.
Other diagnostic problems can result because enlarged lymphocytes, a type of white cell, are common with mono, but can also be a symptom of leukemia. Blood tests can distinguish between the type of white cell seen in leukemia and that with mono.
If your throat is sore, having a throat culture is usually a good idea for several reasons. First, the symptoms of mono and strep infection (including that caused by Strep-A, a particularly serious form of strep) are very similar. Second, strep throat or other throat infections can develop anytime during or shortly after in the disease. In any case, it's important that throat infections be diagnosed as soon as possible and treated with antibiotics that can kill the organism responsible for the infection.
The test most commonly used to tell whether you have mono or some other ailment is the mononucleosis spot test. This blood test detects the antibodies (proteins) that the body makes to fight EBV or CMV. Because it takes a while for antibodies to develop after infection, your doctor may need to order or repeat the test one to two weeks after you develop symptoms. At that time the test is about 85 percent accurate.
Other tests your doctor might order include a complete blood count (CBC) to see if your blood platelet count is lower than normal and if lymphocytes are abnormal, and a chemistry panel to see if liver enzymes are abnormal.
Bed rest is the most important treatment for uncomplicated mono. It's also important to drink plenty of fluids. Mono is not usually a reason to quarantine students. Many people are already immune to the viruses that cause it. But if you have mono you'll want to stay in bed and out of classes for several days, until the fever goes down and other symptoms abate. Even when you've started to get better, you can expect to have to curtail your activities for several weeks, and it can take two to three months or more until you feel your old self again.
The author of this article had mono herself when she was 16. Though she didn't mind getting out of all that homework (or at least putting it off), having to delay finals only added to her anxiety about college applications that many high school juniors experience. And then there was that guy who never called again.
When you add the time spent recuperating to the fact that most people are not exactly anxious to get close to a person with mono, you can understand why some students find themselves combating loneliness on top of their other troubles.
Getting through mono may be both challenging and depressing—and seem to take forever. But if you rest when your body tells you to, you can lessen the chances of complications and get back your life.
Judith Levine Willis
WILLIS, JUDITH LEVINE. “MONO: TOUGH FOR TEENS AND TWENTY-SOMETHINGS.” FDA CONSUMER (MAY, JUNE 1998): 32,3.
See AlsoBlood Supply and Infectious Disease; Cancer and Infectious Disease; Childhood Infectious Diseases, Immunization Impacts; Demographics and Infectious Disease; Viral Disease.
BIBLIOGRAPHY
Books
Collier, L., and J. Oxford. Human Virology. New York: Oxford University Press, 2006.
Mandell, G.L., J.E. Bennett, and R. Dolin. Principles and Practice of Infectious Diseases. 6th ed. Philadelphia: Elsevier, 2004.
Tselis, A., and H.B. Jenson. Epstein-Barr Virus. New York: Taylor & Francis, 2006.
Umar, C.S. New Developments in Epstein-Barr Virus Research. New York: Nova Science Publishers, 2006.
Web Sites
Centers for Disease Control and Prevention. “Epstein-Barr Virus and Infectious Mononucleosis.” 2007. <http://www.cdc.gov/ncidod/diseases/ebv.htm> (accessed March 7, 2007).