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Glandular Fever: A Comprehensive analysis

General, Immune | May 26, 2015 | Author: The Super Pharmacist

general, Immune

Glandular Fever: A Comprehensive analysis

Glandular fever is a type of viral infection which is also known as infectious mononucleosis (IM) or “mono.”  Glandular fever affects around 1 in 200 people during their lives and mostly affects young adults aged between 15 and 24. Clinical infection is most common in populations with many young adults, such as active-duty military personnel and college students. 

Sometimes called the kissing disease, glandular fever is spread through a person's saliva, through kissing, coughing, and sneezing and shared cutlery and crockery, such as cups, plates, and utensils. However, these viruses can also spread through blood and semen during sexual contact, blood transfusions, and organ transplantations. The virus can even be spread by sharing things like lip gloss, lipstick, or lip balm.

A person is most contagious from just before symptoms start until they go away. Epstein-Barr virus (EBV) is the most common cause of glandular fever, but other viruses can also cause this disease. Other infections that can cause glandular fever include:

  • Cytomegalovirus (CMV)
  • Toxoplasmosis HIV
  • Rubells
  • Hepatitis A, B, or C
  • Streptococcal pharyngitis

EBV is classified as a member of the herpes virus family. It is one of the most common viruses that affect humans and is very contagious.

EBV has an incubation period of about one to two months. Incubation period is the time elapsed between initial infection and the appearance of signs and symptoms. 

A person remains contagious for at least two months after initial infection with EBV. Some people can have EBV in their saliva for up to 18 months after infection.

Most EBV infections occur during early childhood. When glandular fever strikes young children, the illness is usually so mild that it passes as a common cold or the flu. Afterwards, the virus will remain in the body for life, lying dormant in a number of throat and blood cells.  

The majority of glandular fever cases, however, occur in teenagers and young people aged between 15 and 25. Not everyone who lives in close proximity to a person infected with glandular fever comes down with the illness. About 95% of adults have been infected with EBV and 50% of kids are infected before age 5. So, it is likely that many persons have had mono but were not even aware of it. 

However, when it occurs during adolescence or adulthood, the disease can be much more serious. Although far more common in children and young adults, the disease can occur at any age. At least 25% of teenagers and young adults who get infected with EBV will develop glandular fever. During the infection, the immune system fabricates antibodies to fight the virus and this then provides lifelong immunity. Therefore, it is rare to have more than one bout of glandular fever.

Symptoms of Glandular Fever

Glandular fever comes on gradually. For some people, especially young children, an EBV infection does not cause any symptoms, whilst others may develop a brief illness that is milder.

The symptoms of glandular fever are common to many infections and mimic the symptoms of a cold, the flu, or strep throat. Symptoms usually develop slowly and may not all occur at the same time. Fatigue is often more severe with mono than with other viral or bacterial illnesses.

Typical symptoms of glandular fever include:

  • Flu-like symptoms. As is the case with many virus infections, glandular fever often causes fever, aches, and headaches.
  • A skin rash can appear in some individuals. The rash is widespread, red, non-itchy.
  • Loss of appetite.
  • Nausea.
  • Malaise. A feeling of intense tiredness and weakness often develops.
  • Sore throat. The tenderness may be mild, but commonly the throat is very sore, red, and swollen. It resembles a bad bout of tonsillitis. Glandular fever is typically suspected when 'tonsillitis' is severe and lasts longer than usual. Swallowing is often painful.
  • Spleen. This organ is under the ribs on the left side of the abdomen and is an important  part of the immune system. Like the lymph glands, it swells and can sometimes be felt below the ribs. Occasionally, it causes mild pain in the upper left section of the abdomen.
  • Swelling around eyes. About 1 in 5 people with glandular fever become quite puffy and swollen around the eyes. This disappears rapidly.
  • Swollen glands. As the body's immune system fights off the virus, the lymph glands swell. Any lymph nodes in the body can be affected, but the glands in the neck and the armpits are usually the most prominent. They can become swollen and tender.
  • No symptoms. This is called a sub-clinical infection. Many people become infected with this virus but do not develop symptoms.
  • The liver can be affected. In some cases, the infection can affect the liver. This can cause jaundice (yellowing of the skin and the eyes). It is more common in people who are over 30 years of age.
  • Mild inflammation of the liver or hepatitis can occur with symptoms such as intolerance to alcohol, loss of appetite, and nausea.

The majority of the symptoms should pass within four to six weeks without treatment. Fatigue, however, can persist beyond that time. In most people, fatigue will end after three months. Occasionally, the disease lingers for a year or so, causing recurrent attacks that gradually become milder. Full recovery is typical.

Diagnosing Glandular Fever

The classic triad of fever, pharyngitis (inflammation of the back of the throat), and lymphadenopathy (enlarged lymph nodes) should alert the clinician to the possibility of glandular fever as the diagnosis. All these symptoms occur in more than half of all patients, particularly in older children and adolescents. These patients usually present with early symptoms of headache, anorexia, malaise, and fatigue. After this period, which typically lasts about a week, the classic triad appears.

Diagnosis of glandular fever is confirmed with blood tests.

Diagnosing Glandular FeverLaboratory diagnosis: Serologic testing is the mainstay of diagnosis of caused by EBV, although interpretation of the laboratory results can be difficult.

Heterophile antibodies: The most rapid testing involves detection of the presence of heterophile antibodies. The heterophile antibodies are not specific for the EB virus.

False positive results: Positivity for the heterophile antibody tests increases during the first six weeks of the illness, and so, test results may be negative early in the course of the disease. 

False-negative results: Reasons for false negative results include:

  • Testing is performed too early in the course of the illness. The false-negative rate is as high as 25% in the first week of infection, 5-10% in the second week and 5% in the third week of infection.
  • Heterophile antibody tests are less sensitive in patients aged younger than 10 years. False-negative results are particularly common in children less than 12 years of age and in the elderly.

EBV-specific antibodies.  If results for heterophile antibodies are negative up to six weeks into the disease, EBV-specific antibodies should be tested. The antibodies tested are developed by the body against proteins that lie within the core of the EB virus. The most useful EBV-specific antibodies are the viral capsid antigens (VCAs) and the EBV nuclear antigen (EBNA).

The Centers for Disease Control and Prevention recommend ordering several tests to help determine whether a person is susceptible to EBV or to detect a recent infection or a prior infection, or a reactivated EBV infection. These tests include:

  • Viral capsid antigen (VCA-IgM)
  • Viral capsid antigen (VCA-IgG)
  • D early antigen (EA-D)
  • Epstein Barr nuclear antigen (EBNA)

Interpretation of EBV-specific antibody tests: If someone is positive for VCA-IgM antibodies, then it is likely that he or she has an EBV infection, and it may be early in the course of the illness. If the person also has symptoms associated with mono, then it is most likely that he will be diagnosed with mono, even if the mono test was negative.

  • If a person has positive VCA-IgG and EA-D IgG tests, then it is highly likely that he has a current or recent EBV infection.
  • If the VCA-IgM is negative but VCA-IgG and an EBNA antibody are positive, then it is likely that the person tested had a previous EBV infection.
  • If an individual is asymptomatic and negative for VCA-IgG, then that person has likely not been previously exposed to EBV and is vulnerable to infection.
  • In general, rising VCA-IgG levels tend to indicate an active EBV infection, while falling concentrations tend to indicate a recent EBV infection that is resolving.

Although in most cases serologic testing is appropriate, given the lapse in time between onset of symptoms and the presentation of a symptomatic patient, on occasion, patients may present more acutely—in a "window" phase between infection and the generation of antibodies. In such patients, it may be useful to evaluate for the presence of EBV in the blood  using a technique called the polymerase chain reaction. The polymerase chain reaction is used to amplify a single copy or a few copies of a piece of DNA by several orders of magnitude. The technique allows for rapid and highly specific diagnosis of infectious diseases, including those caused by the EBV.

Complications of Glandular Fever

The most common serious complications of EBV infection are airway obstruction due to extreme tonsillar enlargement and splenic rupture, which fortunately only occur in about 5% and less than 0.5% of infected patients, respectively. Other complications include:

  • Myocarditis and cardiac conduction abnormalities are rare complications
  • Haemolytic anaemia, thrombocytopenia (low platelet count)
  • Acute insterstitial nephritis, glomerulonephritis
  • Neurological, including optic neuritis, transverse myelitis, aseptic meningitis, encephalitis and meningoencephalitis, cranial nerve palsies (especially facial palsy) or Guillain-Barre syndrome
  • Prolonged fatigue
  • Depression
  • EBV has been linked to the development of several malignancies (eg, (Burkitt's lymphoma, lymphomas associated with immunosuppression, other non-Hodgkin's lymphomas, Hodgkin's disease, nasopharyngeal carcinoma, gastric adenocarcinoma, lymphoepithelioma-like carcinomas, and immunodeficiency-related leiomyosarcoma)

Treating Glandular Fever 

The mainstay of therapy for patients with glandular fever is supportive care. Emphasis is placed on the relief of pain, normalisation of body temperature, hydration, and limitation of physical activity. There are no medications  which directly target the EB virus in glandular fever because antibiotics and antiviral drugs are not effective against the virus. 

Analgesics

Pain control is important during the early stages of glandular fever, especially for those patients whose throat is so sore that it keeps them up at night. Recommended pain management may include nonsteroidal anti-inflammatory drugs, salt water gargles, anesthetic throat lozenges, or viscous lignocaine hydrochloride. Codeine is appropriate for patients who do not respond to non-narcotic pain medication.

Antipyretics

Most clinicians favour paracetamol over aspirin to control fever because of concern that aspirin might increase the risk of haemorrhage into the spleen. Also, children under 16 years of age should not take aspirin because there is a small risk it could trigger a rare but serious health condition called Reye’s syndrome. Fever usually subsides within a week but has been reported to persist for up to 3 weeks.

Fluids and nutrition

Attention to fluid intake is important, especially for febrile patients. Maintaining adequate nutrition is also important but can be challenging because many patients are anorexic during the first week or two of illness. 

Limitation of activities

Patients generally adjust daily activities to the level of their exercise tolerance. When may athletes return to contact sports?

There is no consensus. Because splenic rupture generally occurs between days 4 and 21 of clinical illness, most experts would advise waiting at least 1 month after the onset of illness and until splenomegaly has resolved before returning to athletics. It is often difficult to rely on the physical exam alone to detect the presence of splenomegaly.

Corticosteroids

The use of corticosteroids in glandular fever  appears to be a relatively common practice. However, an evidence-based literature review of 7 studies concluded that there is insufficient evidence to recommend steroids for control of the symptoms of glandular fever. Most authors reserve corticosteroids for the management of complications, such as impending airway obstruction, autoimmune anaemia, and autoimmune thrombocytopenia.

Antiviral Drugs

A number of anti-viral drugs (eg, aciclovir, valaciclovir) have shown efficacy against the EBV in vitro (in the laboratory), but none have demonstrated clinical efficacy in patients.

Vaccines

Development of a prophylactic vaccine is the most important future step toward controlling the consequences of primary EBV infection. However, development of an EBV vaccine has been disappointingly slow.

Novel Treatment Approaches

There is currently no cure for EBV infections and very little success treating glandular fever with drugs. However, a recent study  demonstrated that intravenous injections of high dose vitamin C have direct anti-viral activity and can be successfully used for the treatment of EBV infection. Important findings in the study:

  • High dose (7.5 to 50 grams) intravenous vitamin C therapy may have a positive effect on disease duration and may reduce viral antibody levels.
  • EBV antibody expression correlates with plasma ascorbic acid concentrations and confirmed the depletion of vitamin C during EBV infection.
  • A reduction in viral load levels occurs over time during intravenous vitamin C therapy.

How Can the Spread of Glandular Fever Be Prevented?

There is no need to be isolated from others if a person has glandular fever as most people will already be immune to the Epstein-Barr virus. Patients can return to work, college or school as soon as they feel well enough. There is little risk of spreading the infection to others as long as common sense precautions are taken, such as not kissing other people or sharing drinks, food, utensils, or personal items, like toothbrushes. It is important to thoroughly clean any items that may have been contaminated by saliva until recovery from the illness is complete.

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