DR.SHABNAM - PowerPoint Presentation

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DR.SHABNAM Tehrani Infectious Disease specialiSTShahid Beheshti University of Medical Sciences

Infectious MononucleosisSlide2

DefinitionThe virus is a member of the family Herpesviridae.Epstein-Barr virus (EBV) is the cause of heterophile-positive infectious mononucleosis (IM)

which is characterized by

fever, sore throat,

lymphadenopathy

, and

atypical

lymphocytosis

.

EBV is also associated with several human

tumors

, including

nasopharyngeal carcinoma,

Burkitt's

lymphoma, Hodgkin's disease

, and (in patients with

immunodeficiencies

)

B cell lymphoma.Slide3

EpidemiologyEBV infections occur worldwide. These infections are most common in early childhood, with a second peak during late adolescenceBy adulthood, more than 90% of individuals have been infected and have antibodies to the virus.Slide4

In lower socioeconomic groups and in areas of the world with deficient standards of hygiene (e.g., developing regions), EBV tends to infect children at an early age, and IM is uncommon. In areas with higher standards of hygiene, infection with EBV is often delayed until adulthood, and

IM is more prevalent

.Slide5

…EBV is spread by contact with oral secretions.The virus is frequently transmitted from asymptomatic adults to infants and among young adults by transfer of saliva during kissing. More than 90% of asymptomatic seropositive individuals shed the virus in

oropharyngeal

secretions

EBV has been transmitted by blood transfusion and by bone marrow transplantation

.(rare)Slide6

PathogenesisEBV is transmitted by salivary secretions.The virus infects the epithelium of the oropharynx and the salivary glands and is shed from these cellsThe proliferation and expansion of EBV-infected B cells along with reactive T cells during IM result in enlargement of lymphoid tissue.Cellular immunity is more important than humoral immunity in controlling EBV infectionSlide7

Clinical ManifestationsSigns and Symptoms: -Most EBV infections in infants and young children either are asymptomatic or present as mild pharyngitis with or without tonsillitis. -up to 75% of infections in adolescents present as IM.

-IM

in the elderly presents relatively often as nonspecific symptoms, including

prolonged fever, fatigue,

myalgia

, and malaise.

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pharyngitis, lymphadenopathy, splenomegaly, and atypical lymphocytes are relatively rare in elderly patientsincubation period: in young adults is 4–6 weeks.Slide9

…A prodrome of fatigue, malaise, and myalgia may last for 1–2 weeks before the onset of fever, sore throat, and lymphadenopathy. Fever is usually low-grade and is most common in the first 2 weeks of the illness; however, it may persist for >1 month.Slide10

Signs  Lymphadenopathy % 95 Fever %93 Pharyngitis or tonsillitis %82 Splenomegaly %51 Hepatomegaly %11 Rash %10 Periorbital edema %13 Palatal enanthem

%7

Jaundice %5Slide11

…Lymphadenopathy and pharyngitis are most prominent during the first 2 weeks of the illnesssplenomegaly is more prominent during the second and third weeks.

Lymphadenopathy

most often affects the

posterior cervical nodes

but may be generalized.

Enlarged lymph nodes are frequently

tender and symmetric

but are

not fixed

.Slide12

…Pharyngitis, often the most prominent sign, can be accompanied by enlargement of the tonsils with an exudate resembling that of streptococcal pharyngitis.A morbilliform or papular rash, usually on the arms or trunk, develops in 5% of cases .

Most patients treated with

ampicillin

develop a macular rash; this rash is

not predictive

of future adverse reactions to

penicillinsSlide13

…Slide14

…Most patients have symptoms for 2–4 weeks.malaise and difficulty concentrating can persist for monthsSlide15

Laboratory Findingswhite blood cell count is usually elevated and peaks at 10,000–20,000 during the second or third week of illness. Lymphocytosis is usually demonstrable, with >10% atypical lymphocytesatypical lymphocytes are enlarged lymphocytes that have abundant cytoplasm, vacuoles, and indentations of the cell membraneSlide16

atypical lymphocyteSlide17

…Low-grade neutropenia and thrombocytopenia are common during the first month of illness.Liver function is abnormal in >90% of cases. Serum levels of aminotransferases and alkaline

phosphatase

are usually mildly elevated.

The serum concentration of

bilirubin

is elevated in ~40% of cases.Slide18

ComplicationsMost cases of IM are self-limited.Deaths are very rare and most often are due to: central nervous system (CNS) complications, splenic rupture, upper airway obstruction, or bacterial superinfectionSlide19

CNS complications: develop usually do so during the first 2 weeks of EBV infection.Meningitis and encephalitis are the most common neurologic abnormalities, and patients may present with headache, meningismus, or cerebellar ataxiaSlide20

…Autoimmune hemolytic anemia: occurs in 2% of cases during the first 2 weeks. In most cases, the anemia is Coombs-positive, with cold agglutinins directed against the red blood cell antigen.spleen ruptures:

in <0.5% of cases which is more common among

male

than female patients

may manifest as

abdominal pain, referred shoulder pain, or hemodynamic compromiseSlide21

Hypertrophy of lymphoid tissue in the tonsils or adenoids: can result in upper airway obstruction.Slide22

…Other rare complications associated with acute EBV infection include: hepatitis (which can be fulminant)myocarditis or pericarditis pneumonia with pleural effusioninterstitial nephritis vasculitis

.Slide23

Diagnosisheterophile test : -human serum is absorbed with guinea pig kidney, and the heterophile titer is defined as the greatest serum dilution that agglutinates sheep, horse, or cow erythrocytes. -Tests for heterophile antibodies are positive in 40%

of patients with IM during the

first week

of illness

and in

80–90% during the third week

.

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-Therefore, repeated testing may be necessary, especially if the initial test is performed early.These antibodies usually are not detectable in children <5 years of age, in the elderly, or in patients presenting with symptoms not typical of IMSlide25

monospot test: The commercially available monospot test for heterophile antibodies is somewhat more sensitive than the classic heterophile test.The monospot test is 75% sensitive and 90% specific compared with EBV-specific serologiesSlide26

…EBV-specific antibody testing : used for patients with suspected acute EBV infection who lack heterophile antibodies and for patients with atypical infections .

Anti-VCA

IgM

and

IgG

antibodies

:

- elevated in the serum of more than 90% of patients at the onset of

diseaseSlide27

- Anti-VCA IgM :diagnosis of acute IM because it is present at elevated titers only during the first 2–3 months of the disease - Anti-VCA

IgG

usually

not useful for diagnosis of IM

but is often used to assess past exposure to EBV because it

persists for lifeSlide28

Seroconversion to EBNA positivity : is also useful for the diagnosis of acute infection with EBV. Antibodies to EBNA become detectable relatively late (3–6 weeks after the onset of symptoms) in nearly all cases of acute EBV infection and persist for the lifetime of the patient. Slide29

Differential DiagnosisCMV HIV Toxoplasmosis HHV-6 Streptococcal pharyngitis Viral hepatitis Rubella Lymphoma Drugs (phenytoin, carbamazepine, sulfonamides, or minocycline)Slide30

TreatmentTherapy for IM consists of supportive measures, with rest and analgesiaExcessive physical activity during the first month should be avoided to reduce the possibility of splenic ruptureAcyclovir has had

no significant

clinical impact on IM in controlled trials.

Glucocorticoid

therapy is

not indicated

for uncomplicated IM and in fact may predispose to bacterial

superinfectionSlide31

Glucocorticoid therapy: prevention of airway obstruction in patients with severe tonsillar hypertrophy autoimmune hemolytic anemia hemophagocytic

lymphohistiocytosis

severe thrombocytopenia

Glucocorticoid

therapy have also been administered to rare patients with severe malaise and fever & to patients with severe CNS or cardiac disease.Slide32

PreventionThe isolation of patients with IM is unnecessary.