Herpes viruses(part-II

Herpes viruses:

Epstein-Barr virus(a.k.a human herpesvirus type-4):

EBV is distributed worldwide, with over 90% of adults seropositive . Humans are natural hosts of EBV. The virus is transmitted by exchange of saliva (eg; during kissing ).
Pathogenesis:
EBV initiates infection of oropharyngeal epithelial cells and spreads to cervical lymph nodes, then travels via blood to liver and spleen. EBV infects and become latent in B-lymphocytes, that persists for life.
Clinical pictures:
EBV causes primary infection is infectious mononucleosis(glandular fever) in young adults .The disease has incubation period 30-50 days ,it is characterized by fever ,pharyngitis ,sore throat, lethargy, fatigue ,headache ,malaise, lymphadenopathy ,splenomegaly , and elevated liver enzymes. IM is usually resolving in 1-2 weeks, but fatigue may be persisting for months. Primary EBV infections in children are usually asymptomatic.
EBV is tumor virus (oncogenic), recurrent infection is reactivated and closely linked with Burkitt lymphoma (this disease is common in African children, especially who infected with malaria) , nasopharyngeal carcinoma (the disease is common in south Asia especially in males of Chinese origin, especially who eating salted fish that treated with nitrosamine), and Hodgkin lymphoma disease(common in Europe and Africa).
EBV is also associated with X-linked lymphoproliferative syndrome , and hairy leukoplakia, a whitish lesion on tongue seen especially in AIDS patients.

Lab. Dx :
a. Hematological approach ; EBV mononucleosis is diagnosed by demonstration of atypical lymphocytes(abnormal lymphocytes) in blood smear.
b. Immunological approach ; EBV-specific serologic tests (Paul-Bunnell test) can be used to detect heterophile antibodies that common in EBV infection.
c. Genetic approach : EBV DNA can be detected by PCR.
Control :
• Treatment : There is no specific antiviral therapy for EBV. Acyclovir has little activity against EBV.
• Prevention :There is no vaccine available to prevent EBV infection.
Cytomegalovirus(a.k.a human herpesvirus type-5):

Humans are the natural hosts , whereas ,animal CMV strains do not infect human. CMV infection occur worldwide distribution, it is endemic in all parts of world .
The virus is transmitted from person to person by several different ways. In early life, it is transmitted across placenta, within birth canal, and commonly in breast milk. In young children , its most common mode of transmission is via saliva. Later in life , it is transmitted sexually, and it can also be transmitted during blood transfusion and organ transplants. In other words , the virus is transmitted by contact with body fluids such as ; saliva, urine, semen, breast milk, cervical secretions , and blood.

Pathogenesis :
There are two clinical forms of CMV infection :
1-congenital infection(primary infection) .
2-immunosuppressed individuals(secondary infection).
The virus initial replicate in oropharynx (especially in salivary gland) , it spreads to lymphoid tissues , and produces a viremia , then the virus disseminates systemically to involve multiple organs (liver ,kidney , spleen, lungs,brain). CMV remains latent in mononuclear cells and is reactivated in immunosuppressed patients.
CMV primary infection is cytomegalic inclusion disease in neonates, which characterized by multinucleated giant cells with prominent intranuclear inclusion. Because giant cells are formed ,hence the name cytomegalo. Many organs are affected , and widespread congenital abnormalities result. Infection of fetus occurs in the pregnant women , ie, when she has no antibodies that will neutralize the virus before it can infect the fetus. Congenital abnormalities are more common when a fetus is infected during the first trimester than later in gestation.
CMV primary infection of children and adults are usually asymptomatic .
CMV enters a latent state in leukocytes (monocytes)and can be reactivated when cell-mediated immunity is decreased .

Clinical features:
1- Infants infected with congenital infection by this virus during gestation show clinically manifestations of cytomegalic inclusion disease(CID) such as microcephaly , hepatosplenomegaly ,seizure , deafness, jaundice, and purpura . Cytomegalic inclusion disease is one of leading causes of mental retardation. Infected infants can continue to secrete CMV( shedding) in urine for several years .
2- CMV causes a mononucleosis-like syndrome in older children and adults characterized by persistent fever ,pharyngitis, fatigue, malaise, and lymphadenopathy that is clinically similar to EBV mononucleosis.
3- CMV is opportunistic virus. The virus is common cause pneumonia in immunosuppressed patients who have received transplants . It can causes retinitis(which can lead to blindness) in patients with AIDS, and also causes encephalitis and colitis.

Lab. Dx:
1. CMV can be isolated by cytopathic effects in cell culture.
2. Directed diagnosed by immunoflourescence test for detect CMV-specific antibodies.
3. CMV DNA can be detected in body fluids by PCR.

Control:
• Treatment: Ganciclovir is drug of choice for treatment of CMV infections. The drug is highly toxic . Foscarnet is used to treat CMV infections resistant to ganciclovir.
• Prevention:
1-There is no vaccine available to prevent CMV infections.
2-Barrier contraception and safe sex practice are important preventive measures.


Human herpesvirus type-6 and type-7:

These herpesviruses are less common than others in cause human infections . Transmission of HHV-6 and HHV-7 occurs by saliva.

Pathogenesis and clinical findings:
Both viruses infect T-cells . They have capacity to establish latent infection in T-cells. Reactivation of infection can occur in immunocompromised patients. Both viruses cause exanthema subitum (roseola infantum) in children and is characterized by high fever for 2-5 days, followed by generalized ,maculopapular rash.

Lab.Dx:
1-serologic tests are used to detect virus-specific IgM and IgG.
2-DNA of HHV-6 and HHV-7 can be detected by PCR.

Control :
A. Treatment : There is no specific antiviral therapy for HHV-6 and -7 infection .
B. Prevention : There is no vaccine against these viruses.



Human herpesvirus type-8:

Transmission of HHV-8 is primarily sexually, and by saliva, but it also can be transmitted in transplanted organs.

Pathogenesis and clinical findings:
HHV-8 infects B-lymphocytes and endothelial cells and establishes a latent infection in B cells. The virus encodes many potentially oncogenic producers and cause Kaposi sarcoma (KS), a spindle cell of endothelial origin, characterized by lesions on skin, face, or oral cavity that appear as bruised or discolored spots and that progress to ulcerated nodules. Kaposi sarcoma-associated herpes virus is most common in patients with AIDS.

Lab. Dx:
1. Biopsy of skin lesions for detection of spindle cells.
2. HHV-8 infection is detected by PCR and hybridization with HHV-8-specific probes.

Control :
A. Treatment:
1-There is no specific antiviral therapy for HHV-8 infection . 2-Surgical excision, radiation, and systemic drugs such as alpha interferon, can be used.
B. Prevention : a-There is no vaccine against this virus.
b-Safe sex practice should reduce the risk of transmission .


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