structure/char/genetics of adenovirus

• DNA
• outer covering is protein coat which contains capsomeres aranged in an icosahedral structure
• non enveloped
• more than 50 serotypes
  • many different types associated with different types of clinical symptoms/disease

Unique biological abilities of adenoviruses

• cause tumors in animals and ocncogenically transform cells in tissue cultures
• cause latent infection in several hosts
• induce or inhibit apoptosis through suppression or expression of early viral proteins
• serve as vectors for introducing foreign genes into mammalian cells

• three different interactions
  • lytic infections- occurs in human epithelial cells, result in human cell death and produce many progeny
  • latent or chronic infection- involve lymphoid tissue like in tonsilar infection
  • oncogenic transformation- viral DNA is integrated into host and replicates with cell DNA, but no virons produced

adenovirus: clinical syndromes

• respiratory infections
• pharyngoconjunctival fever
• epidemic keratoconjunctivitis
• hemorrhagic cystitis
• infantile diarrhea
• intussusception
• CNS infection

adenovirus: respiratory infections characteristics/ symptoms

• at least half of infections asymptomatic
• serological survey shows they cause at least 10% of all resp. infections
• usually causes mild phayngitis or tracheitis
• cough, fever, sore throat, rhinorrhea are most common symptoms
• in infants, type 7 cause bronchiolitis and pneumonia

adenoviruses: pharyngoconjunctival fever characteristics

• occurs in small outbreaks
• characterized by:
  • conjunctivitis
  • pharyngitis
  • rhinitis
  • cervical adenopathy
  • fever
• epi- contaminated swimming pools and ponds

adenoviruses: epidemic keratoconjunctivitis characteristics

• frequently bilateral
• may last up to 4 weeks
• periauricular adenopathy is common
• cornea may remain involved for several months and produce visual disturbances
• secondary spread to household contacts is about 10% in most cases

adenovirus: hemorrhagic cystitis characteristics

• 25-50% of all cases of hemorrhagic cystitis in kids due to adenovirus
• more common in boys
• present with hematuria, dysuria, and urinary frequency

adenovirus: infantile diarrhea characteristics

• diarrhea associated with fever
• rotavirus and adenoviruses predominate causes of infantile viral diarrhea

adenovirus: CNS infection characteristics

• sporadic cases of encephalitis and meningoencephalitis

Effect of adenoviruses in immunocompromised hosts: clinical characteristics

• important pathogen in those undergoing bone marrow or solid organ transplantation
• infection frequently involves organ transplanted (hep in liver transpantation, hemorrhagic cystitis in renal transplantation)
• disseminated disease with lung, colon, and CNS involvement can occur
  • disseminated disease is more common in kids and has high mortality
• most frequent manifestation in the immunocompromised host involves lung, liver, UT
• pneumonia is often interstitial and bilateral

dx: adenovirus

• clinical criteria alone (usually dont bother to find out if its something like a cold)
• definitive dx involves:
  • visualization by electron microscopy
  • tirssue culture
  • fourfold rise in serum Ab
  • adenovirus DNA in tissue samples or blood
• Ag can be detected in sputum, nasopharyngeal washes or throat swabs by immunofluorescence or ELISA, which serve as rapid dx tests

tx: adenovirus

• immunocompetent: supportive therapy
• if immunocompromised or severe, antiviral therapy has been attempted with variable success: Cidofovir

prevention of adenovirus

• oral vaccines were developed for use on military recruits contain live virus
• virus not attenuated, but took advantage of fact that infection of GI tract of adults doesnt result in illness
• efficacy and saftey was well established but lack of availability and demand of vaccine resulted in discontinuation of vaccination in 1999

genetics/sturcture/characteristics of Papillomaviruses

• icosahedral capsid composed of capsomeres enclosing a dsDNA that is circular
  • viral genome divided into regions
  • one regulatory region contributes to role of DNA replication and transcription of 8-9 ORF
  • these ORF's are divided into early and late regions, each with its own specialized function
  • gene products of E6, have major transforming properties through binding of various cellular factors and key tumor suppressor proteins
  • E6 bind p53 and accelerate degredation
  • E7 bind tumor suppresor gene products (Rb protein) and inhibits their function

papillomavirus: epidemiology

• cutaneous warts
  • common warts occur in school aged children
  • plantar warts sween frequently in adolescents and young adults
  • flat warts predominantly in children
  • other groups at high risk are butchers, meat packers, fish handlers
• genital warts
  • most commonly acquired viral STD
  • 3/4 of US population is infected

papillomavirus: transmission

• close personal contact for transmission of cutaneous warts
• minor trauma at site of inoculation is also important (high frequency in meat handlers)
• sexual transmission of anogenital warts
• resp. papillomatosis can occur through passage through infected birth canal

papillomavirus: clinical manifestations of cutaneous warts

• deep plantar warts (verrucae plantaris)
  • raised bundles of keratotic fibers
  • shavings reveals punctuate, bleeding blood vessels
  • lesions are often painful and may be on palms
• common warts (verrucae vulgaris)
  • well demarcated, hyperkeratotic papules with rough surface
  • common places: dorsum of hand, btw fingers, around nails
• plane or flat warts (verrucae planae)
  • common in kids
  • appears as slightly elevated papules with irregular contour and smooth surface

papillomavirus: clinical manifestations of anogenital warts

• flesh or gray colored hyperkeratotic papules
• either sessile or attached by a short peduncle
• in men, usually on penile shaft
• in women, usually on posterior introiitis, labia, flat condylomas on cervix
• involvement of perianal area depending on sexual practices
• can lead to cervical intraepithelial neoplasmis
• grade 1 CIN has great likelihood of regression
• risk of progression to invasive cancer is highest with CIN3: 12%

dx of papillomavirus

• cutaneous warts are dx clinically
• anogential warts
  • in women, colonoscopy with application of acetic acid
  • screnning for premalignant lesion with PAP smears
  • detection of HPV DNA
    • sample DNA is reacted with RNA probes in 2 pools that distinguish between high and low risk HPV types

papillomavirus: general clinical manifestations

• cutaneous warts
  • deep plantar warts
  • common warts
  • plane or flat warts
• anogenital warts

papilloma virus tx

• cutaneous warts
  • OTC salicylic and lactic acid applied after hot warter soak
  • occlusive bandages increase tx effectiveness
  • cryotherapy
• anogenital warts
  • podophyllotoxin topical tx (rellapse common)
  • imiquimode cream (induce production of IFN and other cytokines)
  • cryotherapy with liquid nitrogen or cryoprobe
  • CO₂ laser therapy

papilloma virus prevention

• vaccine approved recently
• protect against 4 types of HPV
• currently approved for girls/women
• ideally administered before individual becomes sexually active
• close to 100% efficacy

genetics/structure/char of parvovirus B19

• among smallest known DNA viruses
• virions are nonenveloped
• icosahedral symmetry

pathophysiology of parvovirus B19

• very narrow target range and can only be propagated in human erythroid progenitor cells
• infection leads to an acute, but self limited cessation of RBC production
• patients with normal RBC turnover, short interuption in RBC production doesnt cause anemia
• patients with high RBC turnover (hemolysis, hemolytic syndromes), it can cause aplastic criss
• anemia improves as host immune response develops
• patients who are immunocompromised, infection may persist and lead to chronic pure red cell aplasia (PRCA)

parvovirus B19: epidemiology and transmission

• common in childhood
• by 15, half of children have detectable IgG
• infection also happen in adults
• most common in late winter, spring, and early summer
• spread via resp. route

parvovirus B19: general clinical manifestations

• erythema infectiosum
• arthropathy
• transient aplastic crisis
• pure red cell aplasia

parvovirus B19: clinical manifestations with erythema infectiosum

• aka fifth disease
• symptomatic pts: prodrome of fever, headache, nausea, diarrhea, followed by classic slapped cheek rash
• ther may be second stage of faint, erythematous maculopapular rash on trunk and limbs
• symptoms are immune mediated

parvovirus B19: clinical manifestations of arthropathy

• infected adults, especially women can present with arthralgia or frank arthritis with swelling and stiffness
• usually symmetrical, involving small joints
• symptoms usually last 1-3 weeks
• symptoms may be mistaken with acute RA

parvovirus B19: clinical manifestations of transient aplastic crisis

• usually pts have underlying hemolytic disorders or have conditions such as iron deficiency or are transplant recipients
• acute anemia has been described in hematologically normal persons
• present with dyspnea due to severe anemia and can be severely ill
• pts with this condition are viremic

parvovirus B19: clinical manifestations of pure red cell aplasia

• occurs in pts who are immunodeficient and is a chronic condition
• pts may have congenital immunodeficiency, AIDS, lymphoproliferative disorders, or are transplant recipients
• presents as persistent anemia
• pts lack or have low parvovirus specific Ab response and persistent viremia

parvovirus B19: dx

• both IgM and IgG made in immunocompetent pts
• viremia detected via DNA hybridization tech
• pts with erythema infectiosum are not viremic
  • Ab production (ELISA) used for dx
  • IgM present at time of rash
  • IgG persists throughout life
• pts with transient aplastic crisis and those with pure red cell aplasia, B19 DNA assays are used to detect viremia
  • for the immunocompromised, THEY CANT MAKE AB, SO NO ELISA
• pts with transient aplastic crisis also produce Ab

parvovirus B19: tx

• benign infection that results in lifelong immunity that requires NO THERAPY if immunocompetent
• immunosuppressed patients or persistent infection
  • cessation/lower dose of immunosuppressive therapy
  • if you cant take away/lower dose of immunosuppressants, you administer Ig