Mononucleosis: Symptoms, Causes, Diagnosis and Treatment

Mononucleosis is caused in the vast majority of cases by the Epstein-Barr virus. It is estimated that 9 out of 10 adults have been infected by this pathogen in the world.
Mononucleosis: Symptoms, Causes, Diagnosis and Treatment
Samuel Antonio Sánchez Amador

Written and verified by el biólogo Samuel Antonio Sánchez Amador.

Last update: 02 April, 2021

Infectious mononucleosis (more commonly known by its nickname “kissing disease”) is a contagious disease caused, in most cases, by the Epstein-Barr virus (EBV). This is one of the most widely distributed viral agents in the world, as it’s estimated that 95% of adults between 35 and 40 years of age have contracted it at some point.

Despite the fact that the vast majority of the world’s population has been infected, it should be noted that many of those affected don’t present specific symptoms. If you want to know everything about this curious pathology, we encourage you to continue reading.

What are the causative agents of mononucleosis?

As we’ve said previously, the Epstein-Barr virus is the cause of the vast majority of cases of mononucleosis disease. However, it’s necessary to emphasize that other pathogens also produce similar symptoms in patients. We’re going to show you the particularities of each one in the following article.

Epstein-Barr virus

Mononucleosis is caused by a virus.
The Epstein-Barr virus is linked to many diseases.

The Epstein-Barr virus belongs to the herpes virus family and is one of the most common pathogens in humans, as indicated by the Vircell portal. It’s a double-stranded DNA virus with about 85 genes, whose genetic information is surrounded by a nucleocapsid, which is, in turn, covered by integument and a protein envelope.

When viral infection occurs in adolescence, about 35-50% of patients will develop the medical condition of infectious mononucleosis. On the other hand, children who are exposed to the pathogen are usually asymptomatic or, at most, develop nonspecific febrile symptoms that are often attributed to other conditions.

In any case, it should be noted that this virus isn’t only associated with the aforementioned disease because, to name just one, the Cancer Research UK Center estimates that 200,000 cases of cancer per year are attributed to it. Gastric cancer, nasopharyngeal carcinoma, Hodgkin lymphoma, and other conditions appear to be linked to this infection.


Cytomegalovirus (CMV) infection is another of the viral conditions of the most common Herpes viruses, as it’s estimated that 60 to 90% of the general population have been infected throughout their lives. Like EBV, this pathogen can cause a specific type of infectious mononucleosis.

However, Epstein-Barr virus mononucleosis produces significant pharyngitis (sore throat), whereas this variant doesn’t. As indicated by the MSD Manuals portal, there are other differences in the symptoms of mononucleosis, depending on the agent that causes it.

Toxoplasma gondii

1% of mononucleosis cases are attributable to this parasite. This protozoan (Toxoplasma gondii) is transmitted through the feces of domestic cats, so many people contract toxoplasmosis without realizing it by not effectively sanitizing items that have been in contact with the feline, or by putting their hands to their mouths.

This pathology is asymptomatic in 80-90% of cases. However, in immunodeficient people and fetuses, it can seriously endanger them.

Pathogenesis and immune reaction

The NCBI portal and other professional medical sources help us understand what happens in the patient’s body when infected with the Epstein-Barr virus. We’re going to quickly tell you what this immune reaction consists of.

First of all, you should be aware that viruses can’t reproduce on their own. As they lack cells (and therefore organelles such as mitochondria or ribosomes), they aren’t capable of replicating their genetic information or synthesizing proteins. Therefore, they must infect a host cell and “hijack” its machinery.

Mechanism of contagion

The disease doesn’t follow any pattern of seasonality, but it is more present in children and young adults. This virus is transmitted through saliva, but it isn’t necessary that the contact between an infected patient and a healthy one is very intense in order for the infection to occur.

A small viral inoculation in the form of a kiss on the cheek or salivary sputum could be enough to infect a child.

Replication and response sites

Once the pathogen enters the body, viral replication begins in the pharyngeal cavity (B cells and tonsil epithelium). At some point during the incubation period, the replicated viruses enter the bloodstream and can remain circulating for up to 2 weeks before symptoms appear.

The acute stage of the disease coincides with a peak in viral load in the blood and oral cavity, events that occur simultaneously. The body acts at an immune level to counteract infection, producing IgM antibodies and a large number of CD8 + T lymphocytes, which are activated in response to virus-infected cells.

Active CD8 + T cells recognize infected cells and destroy them. By a succession of physiological events, they induce apoptosis of the target cell, in order to prevent the virus from replicating uncontrollably and ending the physiological equilibrium of the host.

Viruses can’t replicate themselves by mitosis, as our cells can. Therefore, they always need a host to multiply.

Mononucleosis symptoms

So, now you know which agents cause mononucleosis as well as the immune mechanism of the disease. We can now address its symptoms, diagnosis, and treatment. Fortunately, Epstein-Barr virus infection has been extensively studied, so there are many studies that accurately show its symptoms.

The Integral Pediatrics journal and other sources already cited help us to build a list of the clinical symptoms of mononucleosis, including the percentages affected by each symptom. Here’s a breakdown:

  • Sore throat (95%): As we’ve said, the virus begins to replicate in the pharyngeal epithelium, so it isn’t surprising that most of the symptoms are located here in the initial stages. It’s sometimes misdiagnosed as strep throat, but mononucleosis doesn’t respond to antibiotics.
  • Fever (up to 98% in children, 47% in adults): Together with a sore throat, this is usually one of the first symptoms of the disease, especially in infants. It has a remitting or intermittent character and oscillates over a value of 39 degrees.
  • Lymphadenopathy (80%): Tonsils are lymph nodes found at the back of the mouth and high in the throat. Since their role is to fight infection, when EBV infestation arises, these tissues become inflamed. The patient may show a very obvious lump in the throat or neck area.
  • Fatigue (70%): Fatigue during infectious diseases is natural. After all, the body is devoting resources to fighting a pathogen.
  • Upper respiratory tract symptoms (65%).
  • Headache and reduced appetite (50%).
  • Muscle aches (45%).
  • Transient elevation of liver enzymes (75%): This can be considered as typical of subclinical hepatitis.

Considerations and possible complications

These percentages are very general and, in addition, we must emphasize that children and adults respond very differently to infection. However, sore throat and cervical lymphadenopathy (inflammation of the tonsils ) are clinical signs shared by almost all patients.

Symptoms of the disease can last 2 to 4 weeks. However, most of the obvious clinical signs begin to subside 10 days after their appearance. Unfortunately, this infection can also manifest itself with various complications, such as anemia, hepatitis with jaundice, nervous system problems, and even a ruptured spleen.

In general, these complications are seen almost exclusively in people over 35 years of age. Beyond a fever and sore throat, children and young people often don’t have life-threatening symptoms.

Mononucleosis diagnosis

Mononucleosis is diagnosed with laboratory tests.
Multiple laboratory studies are necessary to correctly diagnose the disease.

As the Mayo Clinic indicates, the diagnosis of mononucleosis begins with a physical examination. The professional may be suspicious of the pathology by seeing the swelling of the patient’s tonsils and with their complaints of a sore throat, but a superficial examination isn’t enough.

Because of this, they will ask for a blood test. The following factors will be examined:

  1. More white blood cells than normal: As we’ve said, the concentration of circulating CD8 + T lymphocytes increases significantly during infection.
  2. Strange-looking white blood cells.
  3. Antibody analysis: Those that are looked for are IgM-type immunoglobulins (called heterophile antibodies). These immunoglobulins are the ones produced for the recognition of the virus antigen, present in its capsid (VCA).
  4. Slightly abnormal liver function.

The white blood cell count doesn’t fully confirm the presence of the disease (it may be due to mononucleosis or other types of infections), but the antibody analysis undoubtedly provides the information necessary to correctly categorize the disease.


The goal of treating mononucleosis is to relieve symptoms, since most viral diseases can’t be solved with medications. After all, it is the patient’s own body that must fight and eliminate the pathogen.

Therefore, drugs such as antipyretics are used to combat feverish states (such as acetylsalicylic acid, paracetamol, and ibuprofen). Other drugs that fall into the group of non-steroidal anti-inflammatory drugs (NSAIDs) may also be useful.

If symptoms are severe, prednisone can be given by mouth. This is a synthetic corticosteroid drug that treats fever, asthma, and cough, among other things. As indicated by the US National Library of Medicine, antivirals such as acyclovir have little or no benefit in these cases.

The best allies in the face of a common viral infection are rest and adequate hydration.

Prevention and final care

Preventing mononucleosis is an almost impossible task, as the virus can remain in saliva for months after infection. It’s advisable to avoid kissing anyone during the most intense moments of the disease, but this doesn’t ensure that the contagion won’t occur later.

Therefore, the best advice we can give readers is not to be afraid of this disease. Almost all of us experience mononucleosis throughout our lives, but in very few cases has it become a serious pathology that requires hospital care.

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