Infectious Diseases-Infectious Mononucleosis

Infectious Diseases-Infectious Mononucleosis.

Carl Stuart

Stuart Medical Series

Introduction.

Infectious mononucleosis is a benign, heterophile-positive, self-limited lymphoproliferative condition that is caused by Epstein-Barr Virus (EBV). EBV is an enveloped virus that belongs to the family herpesviridae, and as such it consists of a linear DNA enclosed within a nucleocapsid (Fauci et al, 2012). It has been implicated in the development of nasopharyngeal carcinoma and some types of lymphomas such as B-cell lymphomas, Hodgkin’s disease and Burkitt’s lymphoma (Kutok & Wang, 2006).

The signs and symptoms of the infectious mononucleosis are fever, atypical lymphocytosis (characterized by the presence of mononucleosis cells), tonsillar pharygitis, splenomegaly and generalized lymphadenopathy (Fauci et al, 2012). It has been associated with the following co-morbidities: pneumonitis, hepatitis and meningoencephalitis (Kutok & Wang, 2006).

Studies done in developed western nations have shown that symptomatic infectious mononucleosis occurs during late adolescence and early adulthood, and that its prevalence is high among members of the upper SES (socio-economic status). The highest prevalence rate of the disease is found among college students in their first year.  However, in other parts of the world, the primary infection is asymptomatic, and it occurs during childhood. Studies have also shown that over 90% of all adults have antibodies against EBV, and the seroprevalence is about 100% in the middle-aged population. This explains its low prevalence rates among the adult population (Roberts, 2008).

Transmission of infection.

The main mode of transmission of the EBV pathogens is through oropharygeal secretions contained in the saliva. Research has shown that kissing is main mode of transmission, hence its name, the kissing disease. The peak incidence of the disease is among individuals aged 15-25 years.  Among children, transmission is facilitated by poor personal hygiene and the intense close contact that occurs during normal daily activities. The infections are usually subclinical in nature. These early acquisitions of the infection during childhood facilitate dissemination of the infection till young adulthood. Also, during periods of immunosuppression, an adult can shed the virus and thereby transit it (Roberts, 2008).

Humans are the main reservoirs for the EBV pathogens. The lymph tissue found on the oropharynx acts as the main repository of the EBV pathogens. B-cells are the main reservoir for the virus, since people with X-linked agammaglobulinaemia are neither infected nor do they shed the EBV virus. Currently, no environmental reservoirs of EBV have been isolated. The incubation period for the disease is a month, and thereafter there is a short self-limited clinical course that lasts for 2-6 weeks. Thus it is apparent that an individual can shed the virus and thereafter transmit it for a period of about three months. However, some epidemiological studies have shown that the virus can be shed persistently for a period of over 18 months (Roberts, 2008).

Pathophysiology.

The virus is transmitted during close human contact, especially kissing. Transcytosis or transient infection enables the virus to enter the submucosa of the oropharynx and nasopharynx (Hadinoto, 2008). Then, the EBV viral envelope glycoprotein exhibits a high affinity for the CD 21 (Cluster of Differentiation 21) on B cells located in the oropharygeal and nasopharyngeal submucosal lymphoid tissues.  The B-cell infection is can either be a productive (minority of cases) or latent (majority of cases) infection (Kumar et al, 2010).

IgM antibodies against EBV viral capsid antigens are produced during the early phase of infection (Hadinoto, 2008). Latent infection is established by the expression of the following EBV genes: EBNA1, EBNA2 and LMP1. EBNA1 proteins mediate the binding of the EBV genome to human chromosomes thereby establishing and maintaining the episomal persistence of the viral genome. The proteins derived from LMP1 and EBNA2 do mediate the activation and proliferation of B-cells (Kumar et al, 2010). The activated B-cells thereafter enter into the general circulation whereby it secretes heterophilic antibodies. EBV virus does not react with these heterophilic antibodies (Hadinoto, 2008).

Immunity and the immune response.

 The immune response to the primary EBV infection is mediated by cellular immunity. Cytotoxic CD 8+ T cells and CD16+ NK (Natural Killer) cells mediate the cellular immune response. Reactive proliferation of the EBV-specific cytotoxic CD 8+ T cells within lymphoid tissues leads to atypical lymphocytosis, splenomegaly and generalized lymphadenopathy. The IgM antibodies that were formed undergo isotype switching to form IgG antibodies which mediate immune response during secondary infections. These IgG antibodies persist for the lifetime of the individual, and they thus form the humoral immune response to secondary infections (Kumar et al, 2010).

The fully developed cellular and humoral immunity eliminates the infected B-cells (except those with latent infection), and this prevents shedding of the virus (Hadinoto, 2008). Latent-infection in B-cells is activated during periods of immunosuppression, and the reactivation initiates a multi-step (cell-cycle independent) process that leads to neoplasm such as EBV-associated B-cell lymphomas and Burkitt lymphoma (Kumar et al, 2010).

The Epidemiological triad.

The epidemiological triangle shown above assists the epidemiologist to break the cycle of infections. The interventions that are applied must prevent the person-to-person transmission of the pathogen. The incubation period of infectious mononucleosis links the three vertexes of the triangle.

Infectious disease transmission dynamics.

Based on the epidemiological triangle above, the infection can transmitted to the host through close personal contact, or through direct contact of the host to the virus(as it happens among drug abusers who share the same hypodermic needle). Interventions can thus be applied at three points. The apposite interventions must prevent the transmission of the virus to the environment or to the host (Roberts, 2008). These interventions are described below.

1.      Treatment of infections: The proper treatment of both asymptomatic and symptomatic EBV infections will prevent the shedding of the virus, and its subsequent dissemination through kissing. This will have the effect of eliminating the agent (EBV pathogens) from the epidemiological triad. Thus, the virus cannot enter the environment or directly gain access to another person. This is the most appropriate intervention since it is practicable and it does not have any adverse socio-emotional effects (Roberts, 2008).

2.      Prevention of close personal contact with infected individuals: The infected individual needs to be isolated (or quarantined) and treated properly. Also, all his close contacts must be treated. This will have the effect of eliminating person-to-person transmission of EBV. However, this intervention has several demerits which are stated hereafter. First of all, it does not assure that the individual with be treated properly to complete recovery. Also, since the main means of transmission is kissing, this intervention would interfere with close or intimate relationships among individuals; and it will also interfere with children games (Roberts, 2008).

3.      Immunity: A fully functional and competent immune system would prevent the attachment of the virus to the B-cells (mediated by IgG), thus inhibiting the initial stage of infection. Thus, immunosuppression must be prevented. In case immunosuppression occurs, it must be managed properly with immunomodulators. Also, immunosuppressive drugs must be contraindicated in susceptible individuals. The main disadvantage of immunomodulators is that they may exercabate auto-immune conditions.

Conclusion.

Infectious mononucleosis is a benign, heterophile-positive, self-limited lymphoproliferative condition that is caused by EBV; and it is associated with nasopharyngeal carcinoma, B-cell lymphomas, meningoencephalitis, Hodgkin’s disease, pneumonitis, hepatitis and Burkitt’s lymphoma. The disease is characterized by fever, atypical lymphocytosis, tonsillar pharygitis, splenomegaly and generalized lymphadenopathy. Its prevalence rate is high among children, adolescents and young adults. Humans are the main reservoirs for the EBV pathogens, with the B-cells located in the oropharyngeal and nasopharygeal lymphoid masses serving as the main repository of the EBV pathogens. The epidemiological triangle assists epidemiologists to break the cycle of infections by applying the apposite interventions such as treatment of infections, prevention of close personal contact with infected individuals, and, maintenance of a competent immune system.

References.

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Kumar,V; Abbas, A; Fausto, N & Aster, J. (2010). Robins and Cotran Pathologic Basis of

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