Transcript Human parvovirus B19

Parvoviridae
Parvoviruses
Human Parvovirus B19
( Introduction )
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Human parvovirus B19:
Smallest DNA-containing virus, have a tropism for erythroid progenitor
cell (actively dividing cells), and it cause variety of human diseases.
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Parvoviruses:
Simplest DNA viruses.
Small coding capacity of their genome.
Viral replication is dependent actively replicating host cells.
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Nomenclature:
Human Parvovirus B19.
parvo mean small.
B19, code number of human serum, virus was first discovered.
( History and the discovery of the virus )
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Discovered in 1975.
assays of serum samples for hepatitis B surface antigen, by using
counter-immunoelectrophoresis (CIEP).
Sample number 19 in panel B gave “false-positive” result.
Precipitin line was excised, examined by EM showed the presence of 23
nm particles resembling Parvoviruses.
1985: virus named Human Parvovirus B19.
( Classification of Parvoviruses )
1- Family: Parvoviridae.
2- Subfamilies: two
I. Parvovirinae. (vertebrate ).
II. Densovirinae. (invertebrate).
3- Genera:
Parvovirinae comprise three genera, based on their ability to
replicate:
1- Genus Parvovirus (autonomously).
2- Genus Dependovirus (helper virus).
3- Genus Erythrovirus (only in erythroid cells).
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Human Parvovirus B19 replication occurs only in human
erythrocyte precursors, is the sole member of the erythrovirus
genus.
( Properties of the virus )
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I. Physical properties:
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Virion :
1- Size and shape: Small (20-25 nm), icosahedral, non
enveloped.
2- Virus outer capsid proteins (VP1, VP2).
3- Genome: ss DNA, size 5.5 kb in length.
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II. Biological properties:
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lack of envelope and the limited DNA content, B19 is
extremely resistant to physical inactivation.
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Virus is resistant to:
1- Heat: 56°C for 60 minutes.
2- pH: 3 – 9.
3- lipid solvents: such as ether and chloroform.
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Virus inactivated by:
1- Formalin.
2- ß- propiolactone.
3- Oxidizing agents
( Pathogenesis )
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Source: Human (patients), Respiratory secretion, blood.
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Mood of transmission:
1- Horizontally: Infection is spread by a respiratory route.
2- Parenteral: blood transfusion or infected blood products.
3- Vertically: trans placental transmission from mother to fetus.
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Route of entry:
Respiratory tract.
Directly into blood.
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Spread:
Blood, tropic for human erythroid cells in BM. ( Mitotically active cells for
replication).
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Target receptor (Cells, tissues):
The cellular receptor for B19 is blood group P antigen (globosids).
P antigen is expressed on:
1- Mature erythrocytes.
2- Erythroid progenitors.
3- Megakaryocytes.
4-Endothelial cells.
5- Placenta, Fetal heart and liver.
Tissue : site of viral replication
1- Adult: bone marrow.
2- Fetus: fetal liver.
Mechanism of tissue damage induced by the virus
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I. Direct effects:
Viral replication in the erythroid cells cause cell death and interruption
of RBC production.
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II. Indirect effects:
antibodies to parvovirus result in formation of immune complex which
deposit in tissue and cause damage.
CLINICAL MANIFESTATIONS
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Human Parvovirus B19 Diseases:
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1- Immunocomptenet hosts:
Children: Erythema infectiosum, EI (skin).
Adults: Polyarthralgia arthraitis syndrome (Joints).
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2- Immunocompromised patients:
Pure red cell aplasia (PRCA) result in chronic anemia.
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3- Haematological disorder:
Transient aplastic crisis, TAC.
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4- Intrauterine infection: Fetal infection, manifested by fetal anemia, hydrops
fetalis and death.
Erythema Infectiosum, Polyarthralgia arthritis syndrome
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Children: Erythema Infectiosum, (fifth disease) ( skin rash).
Adults: Polyarthralgia arthritis syndrome (joints).
almost certainly immune complex disorder.
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Incubation period is 4-14 days.
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Entry: respiratory tract.
Spread: one week , viremia is started and persist for about 5 days.
Shedding is the pharynx and nasal secretion.
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Disease is biphasic illness with symptoms during viremic and immune complex
mediated stage.
1- First phase ( viremic stage): occur at the end of the first week and associated
clinically with:
Flu-like illness (fever, coryzia, headache, myalgia).
GIT symptoms: mild (nausea and diarrhea).
2- Second phase : ( immune complex deposition in tissue ):
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Children (EI): skin rash maculopapular, affect the face (facial rash ), limb, trunk,
resolves in a week.
Adults (Polyarthralgia arthritis syndrome):
Clinically (joints): arthritis, symmetrical and peripheral, wrists, hands and knees.
resolves in 3 weeks.
some arthritis (non destructive) remain months or years.
2- Pure red cell aplasia (PRCA)
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B19 infection in patients with immunodeficiency diseases
like:
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1- Congenital immunodeficiency.
2- Human immunodeficiency virus.
3- Acute lymphocytic leukemia
4- Organ transplants.
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Mechanism:
Patients unable to eliminate B19 infection, because they
cannot produce adequate levels of virus-specific
antibodies.
Result is persistent infection with destruction of erythroid
precursor cells in the BM and chronic anemia.
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Cured or controlled: by immunoglobulin therapy.
3- Transient Aplastic Crisis (TAC)
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Patients with chronic hemolytic disease, result in TAC.
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Chronic hematological disease include:
1- Chronic hemolytic anemia (sickle cell disease, thalassemias).
2- Idiopathic thrombocytopenic purpura.
3- BM transplantation.
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Mechanisms:
The infection lowers the production of erythrocytes, causing reduction
in the hemoglobin level of peripheral blood.
The temporal arrest of production of red blood cells becomes apparent
only in patient with chronic hemolytic anemia because of the short life
span of their erythrocytes.
Clinically:
anemia (pallor, weakness), may need blood transfusion.
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4- Fetal and Congenital Infection
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Maternal infections, serious risk to the fetus.
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Infected fetus may severely affected because:
1- Red blood cell turnover is high.
2- Immune response is deficient, result in persistent viral infection.
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Clinically:
1- Severe anemia, hydrops fetalis.
2- Fetal death and fetal loss:
occur in less than 10% of primary maternal infections.
commonly before 20th week of pregnancy (first and second trimester).
Third trimester effective fetal immune response to the virus account
for decrease in fetal loss at this stage of pregnancy.
3- No evidence that parvovirus B19 infection cause congenital physical
abnormalities.
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Laboratory Diagnosis
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I. Detection of viral DNA : most sensitive test,
Samples: respiratory secretions, serum, and tissue sample( B.M ).
Techniques:
1- Dot Blot hybridization of serum or tissue extract.
2- In-situ hybridization of fixed tissue.
3- PCR: amplification and detection of viral nucleic acid.
II. Serology for detection of serum antibodies:
Types:
1- B19-specific IgM ( indicate recent infection), detected for up to 3
months after the onset.
2- B19 IgG antibodies ( past infection), lasts longer and detectable
lifelong following infection.
Diagnostic importance of serum antibodies:
I. B19-specific IgM.
II. Rising titer of B19 specific IgG.
Techniques:
Enzyme-Linked immunosorbent assay (ELISA).
III- Culture:
Failed to grow in conventional cell culture lines.
Replicate only in human erythroid progenitor cells culture.
EPIDEMIOLOGY
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Transmission: respiratory or through blood and blood
products.
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Seasonal:
commonly as outbreaks of erythema infectiosum in schools
during winter and spring months.
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Rate of infection: Common
60% of adults possess serum antibodies.
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Prevention:
1- Interruption of virus transmission (respiratory) so patients
with TAC and PRCA, should be separated from high risk
patients.
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2-No vaccine for B19 is currently available.
HUMAN PAPILLOMAVIRUS INFECTIONS
(HPVs)
Family: Papillomaviridae.
Genus: Papillomavirus.
Members: Human papillomaviruses (HPVs).
HPV was named because of an association with small epithelial
proliferations:
'Papilla' = nipple (Latin).
'Oma' = tumour (Greek).
HPVs selectively infect the epithelium of the skin and mucous
membranes. These infections may be asymptomatic, produce
warts, or be associated with a variety of benign and malignant
neoplasias.
100 HPV types occur.
Characteristics of the virus
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1- Nonenveloped, icosahedral in shape.
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2- Size: measure 50 to 55 nm in diameter.
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3- Genome: ds DNA, circular genome, about 7.9 kbp.
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4- Capsids: composed of 72 capsomeres, capsomers
located at each of the 12 vertices, are pentavalent and
the other 60 capsomers are hexavalent .
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5- Replicated in nucleus, stimulate cell DNA synthesis,
and viral oncoproteins interact with cellular tumor
suppressor proteins.
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6- Oncogenic potential: significant cause of human
cancer especially cervical cancer.
PATHOGENESIS
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Source: skin lesion, new lesions are probably more infective than older.
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Transmission: Spread is via direct contact, genital area transmitted via
sexual route.
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Target: HPV are highly tropic for epithelial cells of the skin and mucous
membrane. All types of squamous epithelium can be infected by HPV.
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Replication of HPV: begins with the infection of basal cells.
As cellular differentiation proceeds, HPV DNA replicates and is
transcribed. Ultimately, virions are assembled in the nucleus and released
when keratinocytes are shed.
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This process is associated with proliferation of all epidermal layers except
the basal layer and produces hyperkeratosis.
Histologically normal epithelium may contain HPV DNA, and residual
DNA after treatment can be associated with recurrent disease.
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CLINICAL MANIFESTATIONS
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Incubation period of HPV disease is usually 3 to 4 months, up to 2 years.
These infections may be:
1- Asymptomatic.
2- Produce warts.
3- Associated with a variety of benign and malignant neoplasia.
The clinical manifestations of HPV infection depend on the location of
the lesions and the type of virus.
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Warts in humans, including:
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1- Skin warts (Common warts ): benign, usually occur on the hands as flesh-colored
to brown, often regress spontaneously. (HPV 2,4,27,57).
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2- Planter warts: painful. (HPV 1).
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3- Flat wart: common among children, face, neck, chest, and flexor surfaces of the
forearms and legs. ( HPV 3,10, 28).
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4- Anogenital warts (genital condyloma):
sexually transmitted genital lesions
skin and mucosal surfaces of the external genitalia and perianal areas.
caused by specific types of papillomavirus 6,11,40, 42-44,54, types HPV16 and
HPV18, regularly become malignant if they persist for a sufficiently long time.
5- Laryngeal papilloma type HPV6, HPV11. , children.
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Types of anogenital cancer and HPV
types:
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I. Cervical cancer:
Strong association: HPV16, 18, 31, 45
Moderate association: HPV 33, 35, 39, 51, 52,
56, 58, 59, 68
Weak or no association: HPV 6, 11, 26, 42, 43,
44, 53, 54, 55, 62
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II. Vulvar cancer: HPV 16.
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III. Penile cancer: HPV 16.
DIAGNOSIS
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I. Clinical diagnosis: Most warts that are visible to the naked eye can
be diagnosed clinically alone.
II. Laboratory diagnosis:
1- The most sensitive and specific methods :
the polymerase chain reaction or the hybrid capture assay to detect
HPV nucleic acids and to identify specific virus types.
2- Serologic techniques to diagnose HPV infection are in the early stages
of development and are not yet widely available.
3- Culture: HPV cannot be efficiently propagated in cell culture:
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Treatment
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Frequently used therapies include cryosurgery, application of caustic
agents, surgical excision, and ablation with a laser.
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Topical antimetabolites such as 5-fluorouracil also have been used.
Both failure and recurrence have been well documented with all of
these methods of treatment.
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Various interferon preparations have been employed with modest
success.
Prevention:
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HPV vaccine.
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I. Prophylactic vaccination.
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II. Therapeutic vaccines: develop therapeutic vaccines to treat people infected with
HPVs.
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HPV vaccine is an inactivated virus particles (not live) vaccine
which protects against 4 major types of HPV.
These include:
2types that cause about 70% of cervical cancer (HPV 16 and 18) and 2 types that
cause about 90% of genital warts (HPV 6 and 11)..
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HPV vaccine can prevent most genital warts and most cases of cervical cancer.
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Protection from HPV vaccine is expected to be long-lasting.