Case 17- Herpes Flashcards
Herpesviridae virus family
- Herpes simplex virus (HSV) 1 and 2
- Varicella Zoster virus (VZV)
- Cytomegalovirus (CMV)
- Human herpes virus 6 (HHV6)
- Human herpes virus 7 (HHV7)
- Epstein Barr Virus (EBV)
- Human Herpes Virus 8 (HHV8)- Kaposi’s sarcoma associated herpes virus
CMV life cycle
Primary infection –> Latency –> Reactivation
CMV pathogenesis
Lytic replication and host immune response. Latency in a number of blood cells i.e. Lymphocytes. T cell based immunity is important.
CMV
Seroprevalence- 40% for young adults
Transmission is via direct contact with infected secretions (saliva, sexual, blood). Can be congenital
CMV- Infection in immunocompetent patients
- Primary infection- usually asymptomatic. Can get Lymphadenopathy, Hepatitis, General malaise and headache
- Reactivates intermittently throughout life- asymptomatic, virus excreted in urine and saliva
- Long term association (maybe from chronic inflammation)- atherosclerosis, immune senescence
Congenital CMV
- CMV can cross the placenta
- The virus is transmitted from mother to baby during pregnancy
- Normally asymptomatic but can get IUGR, jaundice, hepatosplenomegaly, encephalitis, SNHL
- 20% mortality
- You get serious neurological problems in the survivors
- Some who are asymptomatic at birth get later problems like hearing loss and developmental delays
- Leading cause of non genetic SNHL (Sensorineural hearing loss)
What causes CMV infection in immunocompromised patients
- Solid Organ transplant recipients especially lungs- greatest risk is when the donor is positive and the recipient negative, results in primary infection
- Stem Cell (Bone marrow) transplant recipients- greatest risk is when the donor is negative and the recipient is positive. The recipient has CMV but the bone marrow contains no CMV specific T cells to control it.
- AIDS (especially GI tract and retinitis)
- Biological agents
Types of CMV infections in the immunocompromised
- CMV syndrome- fever, neutropenia, unspecific
* Organ invasive disease- Retinitis, Pneumonitis. Hepatitis, Encephalitis. Myocarditis, GI disease
Diagnosing CMV
- Serology- CMV IgM and IgG
- Molecular- detection of viral DNA by PCR in bodily fluids. It can be found in the blood in immunocompromised people, in the urine/amniotic fluid for congenital infections and sometimes in the tissues
- Histology- Owl’s eye (Cowdry bodies) inclusion bodies
Treatment of CMV
- Ganciclovir (only IV)- inhibits viral DNA polymerase. Requires activation by a viral enzyme. Valganciclovir (oral) is a prodrug with better bioavailability
- Ganciclovir is more toxic then acyclovir- myelosuppressive, nephrotoxic and teratogenic
- Second line- Foscarnet and cidofovir
CMV- when do you treat
- Immunocompetent- treatment not required unless in very specific circumstances
- Congenital infection- Ganciclovir is given to symptomatic babies, it can reduce hearing loss later in life. Use acyclovir in pregnancy
- Immunosuppressed- reduce immunosuppression if possible, give IV ganciclovir or oral valganciclovir
Prevention of CMV
- Prophylaxis- give oral valganciclovir for several months post transplant, Letermovir
- Pre-emptive monitoring- monitor CMV in the blood, if detected give treatment
Epstein Barr virus
Primary infection -> Latency -> Reactivation
Can replicate in a wide range of cell type including B lymphocytes and epithelial cells. 95% seropositive by 40. Transmission is via direct contact with infected secretions (saliva). The means peaks of incidence are in childhood and adolescence.
Epstein Barr virus age
- Young children- usually asymptomatic, can present with sore throat
- Adolescence- infectious Mononucleosis, may be asymptomatic
Infectious mononucleosis
Mono/glandular fever
Mono symptoms
• Low grade fever
• Lymphadenopathy
• Sore throat (viral tropism for epithelial cells)
Abnormal liver function- mild transaminitis. Splenomegaly which can lead to Splenic rupture. Malaise, anorexia, tiredness. The incubation period is 1-2 months.
Diagnosis of primary EBV
Monospot test, EBV serology (IgM and IgG). Atypical lymphocytes as seen on histology/blood film (T lymphocytes reacting to EBV infected B lymphocytes)
Monospot test- EBV
Detects heterophile antibodies, causes clumping of red blood cells Low sensitivity in young children and in the first week (false negatives), low specificity in adults (false positives).
EBV treatment
Usually self-limited, no effective antivirals or vaccines
Reactivation of EBV
Reactivates intermittently through life, normally asymptomatic unless immunocompromised. Virus is excreted in the saliva. EBV is associated with some cancers.
EBV and cancer
- Burkitt’s lymphoma
- Nasopharyngeal carcinoma
- Post-transplant lymphoproliferative disorder (PTLD)
- Other associations- Hodgkins lymphoma, HIV associated lymphoma
Burkitt’s lymphoma
Highly malignant cancer associated with B cells, rapidly growing. Endemic form- seen mostly in young children from Africa, arises most often in the jaw. Sporadic/immunodeficiency forms- less associated with EBV, occurs in the abdomen, bone marrow and CNS. No benefit from antivirals.
Nasopharynngeal carcinoma
Rare, EBV associated tumour of the head and neck. Antivirals dont help
Post-transplant lymphoproliferative disorder
Reduced T cell immunity -> uncontrolled EBV replication -> B cell proliferation -> PTLD. Occurs with reduced T cell immunity, seen in the first year after transplantation. Normally after primary EBV. Treatment- Rituxamab.
HHV6 virus
Two different types of HHV6 virus- A and B.
More then 90% of people are infected by HHV6 by 2. Transmission is via direct contact with infected secretions (saliva) i.e. at nursery. Peak infections 9-21 months
HHV7
Similar clinical features to HHV6
What does HHV6 infect
It infects mononuclear cells in the blood, salivary glands and CNS. Can integrate itself into the host DNA in gremlin cells- chromosomal integration.
Roseola infantum
Rash illness in infants. HHV6/7 is the most common cause, Enterovirus, Adenovirus and Parainfluenzavirus can also be a cause. The rash appears as fever settles, very mild or asymptomatic.
Complications- febrile convulsions (primary infection), Encephalitis (primary infection)
At risk groups for Roseola infantum
Immunocompromised (primary or reactivation). This can cause a generalised infection, Organ-specific disease namely encephalitis, Bone marrow engraftment failure and risk of CMV reactivation.
HHV8 i.e. Karposi’s Sarcoma Associates virus
30% general population serotypes. Disease may not develop. Antiviral therapy has no benefit. You get Kaposi’s sarcoma in HIV infected individuals. Kaposi’s sarcoma is endemic in areas of Africa (not associated with HIV).
Progresses from flat patches to plaques, nodules and tumours.
Rare diseases caused by HHV-8
Primary effusion lymphoma, Multicentric Castleman’s disease
