infectious mononucleosis infectious mononucleosis infectious mononucleosis (im, mono), also known as glandular fever, is an infection usually caused by the epstein–barr virus (ebv). most people are infected by the virus as children, when the disease produces few or no symptoms. in young adults, the disease often results in fever, sore throat, enlarged lymph nodes in the neck, and fatigue. most people recover in two to four weeks; however, feeling tired may last for months. the liver or spleen may also become swollen, and in less than one percent of cases splenic rupture may occur. "mononucleosis" redirects here. for excessive monocyte counts more generally, see monocytosis. infectious mononucleosisother namesglandular fever, pfeiffer's disease, filatov's disease, kissing diseaseswollen lymph nodes in the neck of a person with infectious mononucleosisspecialtyinfectious diseasesymptomsfever, sore throat, enlarged lymph nodes in the neck, fatiguecomplicationsswelling of the liver or spleenduration2–4 weekscausesepstein–barr virus (ebv) usually spread via salivadiagnostic methodbased on symptoms and blood teststreatmentdrinking enough fluids, getting sufficient rest, pain medications such as paracetamol (acetaminophen) and ibuprofenfrequency45 per 100,000 per year (u.s.) while usually caused by the epstein–barr virus, also known as human herpesvirus 4, which is a member of the herpesvirus family, a few other viruses may also cause the disease. it is primarily spread through saliva but can rarely be spread through semen or blood. spread may occur by objects such as drinking glasses or toothbrushes or through a cough or sneeze. those who are infected can spread the disease weeks before symptoms develop. mono is primarily diagnosed based on the symptoms and can be confirmed with blood tests for specific antibodies. another typical finding is increased blood lymphocytes of which more than 10% are atypical. the monospot test is not recommended for general use due to poor accuracy. there is no vaccine for ebv, though promising vaccine research results exist. infection can be prevented by not sharing personal items or saliva with an infected person. mono generally improves without any specific treatment. symptoms may be reduced by drinking enough fluids, getting sufficient rest, and taking pain medications such as paracetamol (acetaminophen) and ibuprofen. mononucleosis most commonly affects those between the ages of 15 to 24 years in the developed world. in the developing world, people are more often infected in early childhood when there are fewer symptoms. in those between 16 and 20 it is the cause of about 8% of sore throats. about 45 out of 100,000 people develop infectious mono each year in the united states. nearly 95% of people have had an ebv infection by the time they are adults. the disease occurs equally at all times of the year. mononucleosis was first described in the 1920s and is colloquially known as "the kissing disease". signs and symptoms main symptoms of infectious mononucleosis exudative pharyngitis in a person with infectious mononucleosis rash from using penicillin while infected with im maculopapular rash from amoxicillin use during ebv infection the signs and symptoms of infectious mononucleosis vary with age. children before puberty, the disease typically only produces flu-like symptoms, if any at all. when found, symptoms tend to be similar to those of common throat infections (mild pharyngitis, with or without tonsillitis). adolescents and young adults in adolescence and young adulthood, the disease presents with a characteristic triad: fever – usually lasting 14 days; often mild sore throat – usually severe for 3–5 days, before resolving in the next 7–10 days. swollen glands – mobile; usually located around the back of the neck (posterior cervical lymph nodes) and sometimes throughout the body. another major symptom is feeling tired. headaches are common, and abdominal pains with nausea or vomiting sometimes also occur. symptoms most often disappear after about 2–4 weeks. however, fatigue and a general feeling of being unwell (malaise) may sometimes last for months. fatigue lasts more than one month in an estimated 28% of cases. mild fever, swollen neck glands and body aches may also persist beyond 4 weeks. most people are able to resume their usual activities within 2–3 months. the most prominent sign of the disease is often the pharyngitis, which is frequently accompanied by enlarged tonsils with pus—an exudate similar to that seen in cases of strep throat. in about 50% of cases, small reddish-purple spots called petechiae can be seen on the roof of the mouth. palatal enanthem can also occur, but is relatively uncommon. a small minority of people spontaneously present a rash, usually on the arms or trunk, which can be macular (morbilliform) or papular. almost all people given amoxicillin or ampicillin eventually develop a generalized, itchy maculopapular rash, which however does not imply that the person will have adverse reactions to penicillins again in the future. occasional cases of erythema nodosum and erythema multiforme have been reported. seizures may also occasionally occur. complications spleen enlargement is common in the second and third weeks, although this may not be apparent on physical examination. rarely the spleen may rupture. there may also be some enlargement of the liver. jaundice occurs only occasionally. it generally gets better on its own in people who are otherwise healthy. when caused by ebv, infectious mononucleosis is classified as one of the epstein–barr virus–associated lymphoproliferative diseases. occasionally the disease may persist and result in a chronic infection. this may develop into systemic ebv-positive t cell lymphoma. older adults infectious mononucleosis mainly affects younger adults. when older adults do catch the disease, they less often have characteristic signs and symptoms such as the sore throat and lymphadenopathy. instead, they may primarily experience prolonged fever, fatigue, malaise and body pains. they are more likely to have liver enlargement and jaundice. people over 40 years of age are more likely to develop serious illness. (see prognosis.) incubation period the exact length of time between infection and symptoms is unclear. a review of the literature made an estimate of 33–49 days. in adolescents and young adults, symptoms are thought to appear around 4–6 weeks after initial infection. onset is often gradual, though it can be abrupt. the main symptoms may be preceded by 1–2 weeks of fatigue, feeling unwell and body aches. cause epstein–barr virus about 90% of cases of infectious mononucleosis are caused by the epstein–barr virus, a member of the herpesviridae family of dna viruses. it is one of the most commonly found viruses throughout the world. contrary to common belief, the epstein–barr virus is not highly contagious. it can only be contracted through direct contact with an infected person's saliva, such as through kissing or sharing toothbrushes. about 95% of the population has been exposed to this virus by the age of 40, but only 15–20% of teenagers and about 40% of exposed adults actually develop infectious mononucleosis. cytomegalovirus main article: human betaherpesvirus 5 about 5–7% of cases of infectious mononucleosis is caused by human cytomegalovirus (cmv), another type of herpes virus. this virus is found in body fluids including saliva, urine, blood, and tears. a person becomes infected with this virus by direct contact with infected body fluids. cytomegalovirus is most commonly transmitted through kissing and sexual intercourse. it can also be transferred from an infected mother to her unborn child. this virus is often "silent" because the signs and symptoms cannot be felt by the person infected. however, it can cause life-threatening illness in infants, people with hiv, transplant recipients, and those with weak immune systems. for those with weak immune systems, cytomegalovirus can cause more serious illnesses such as pneumonia and inflammations of the retina, esophagus, liver, large intestine, and brain. approximately 90% of the human population has been infected with cytomegalovirus by the time they reach adulthood, but most are unaware of the infection. once a person becomes infected with cytomegalovirus, the virus stays in their body fluids throughout the person's lifetime. transmission epstein–barr virus infection is spread via saliva, and has an incubation period of four to seven weeks. the length of time that an individual remains contagious is unclear, but the chances of passing the illness to someone else may be the highest during the first six weeks following infection. some studies indicate that a person can spread the infection for many months, possibly up to a year and a half. pathophysiology the virus replicates first within epithelial cells in the pharynx (which causes pharyngitis, or sore throat), and later primarily within b cells (which are invaded via their cd21). the host immune response involves cytotoxic (cd8-positive) t cells against infected b lymphocytes, resulting in enlarged, atypical lymphocytes (downey cells). when the infection is acute (recent onset, instead of chronic), heterophile antibodies are produced. cytomegalovirus, adenovirus and toxoplasma gondii (toxoplasmosis) infections can cause symptoms similar to infectious mononucleosis, but a heterophile antibody test will test negative and differentiate those infections from infectious mononucleosis. mononucleosis is sometimes accompanied by secondary cold agglutinin disease, an autoimmune disease in which abnormal circulating antibodies directed against red blood cells can lead to a form of autoimmune hemolytic anemia. the cold agglutinin detected is of anti-i specificity. diagnosis infectious mononucleosis, peripheral smear, high power showing reactive lymphocytes splenomegaly due to mononucleosis resulting in a subcapsular hematoma splenomegaly due to mononucleosis resulting in a subcapsular hematoma diagnostic modalities for infectious mononucleosis include: person's age, with highest risk at 10 to 30 years. medical history, such as close contact with other people with infectious mononucleosis, and the presence and time of onset of "mononucleosis-like symptoms" such as fever and sore throat. physical examination, including palpation of any enlarged lymph nodes in the neck, or enlarged spleen. the heterophile antibody test is a screening test that gives results within a day, but has significantly less than full sensitivity (70–92%) in the first two weeks after clinical symptoms begin. serological tests take longer time than the heterophile antibody test, but are more accurate. physical examination the presence of an enlarged spleen, and swollen posterior cervical, axillary, and inguinal lymph nodes are the most useful to suspect a diagnosis of infectious mononucleosis. on the other hand, the absence of swollen cervical lymph nodes and fatigue are the most useful to dismiss the idea of infectious mononucleosis as the correct diagnosis. the insensitivity of the physical examination in detecting an enlarged spleen means it should not be used as evidence against infectious mononucleosis. a physical examination may also show petechiae in the palate. heterophile antibody test main article: heterophile antibody test the heterophile antibody test, or monospot test, works by agglutination of red blood cells from guinea pigs, sheep and horses. this test is specific but not particularly sensitive (with a false-negative rate of as high as 25% in the first week, 5–10% in the second, and 5% in the third). about 90% of diagnosed people have heterophile antibodies by week 3, disappearing in under a year. the antibodies involved in the test do not interact with the epstein–barr virus or any of its antigens. the monospot test is not recommended for general use by the cdc due to its poor accuracy. serology serologic tests detect antibodies directed against the epstein–barr virus. immunoglobulin g (igg), when positive, mainly reflects a past infection, whereas immunoglobulin m (igm) mainly reflects a current infection. ebv-targeting antibodies can also be classified according to which part of the virus they bind to: viral capsid antigen (vca): anti-vca igm appear early after infection, and usually, disappear within 4 to 6 weeks. anti-vca igg appears in the acute phase of ebv infection, reaches a maximum at 2 to 4 weeks after onset of symptoms and thereafter declines slightly and persists for the rest of a person’s life. early antigen (ea) anti-ea igg appears in the acute phase of illness and disappears after 3 to 6 months. it is associated with having an active infection. yet, 20% of people may have antibodies against ea for years despite having no other sign of infection. ebv nuclear antigen (ebna) antibody to ebna slowly appears 2 to 4 months after the onset of symptoms and persists for the rest of a person’s life. when negative, these tests are more accurate than the heterophile antibody test in ruling out infectious mononucleosis. when positive, they feature similar specificity to the heterophile antibody test. therefore, these tests are useful for diagnosing infectious mononucleosis in people with highly suggestive symptoms and a negative heterophile antibody test. other tests elevated hepatic transaminase levels are highly