Viruses Flashcards
Cytomegalovirus infections (CMV)
Double-stranded DNA virus; member of the Herpesviridae family
Symptomatic CMV disease in immunocompromised individuals affects almost every organ of the body
CMV is transmitted from person to person via close contact
CMV pneumonia
0-6% adults with mononucleosis syndrome develop pneumonia
CMV pneumonia is found on CXR; no clinical significance, rapidly resolving with resolution of primary infection
Life-threatening CMV pneumonia occurs immunocompromised patients (lung transplant recipients have a 50% risk of developing CMV illness)
Cytomegalovirus hepatitis
Elevated bilirubin and/or liver enzymes w/ CMV detected
Most common with primary CMV infection & mononucleosis
Mild & transient LFT elevation, rarely hyperbilirubinemia
Cytomegalovirus gastritis and colitis
CMV may infect the GI tract from the oral cavity through the colon
Typical manifestation of disease is ulcerative lesions (oral lesions indistinguishable from HSV or aphthous ulcers)
Gastritis may present as pain or hematemesis
Colitis usually presents as diarrhea
Cytomegalovirus retinitis
Common opportunistic infection in persons with AIDS, typically those with CD4+lymphocyte counts below 50 cells/µL
Cases have decreased with the use of HAART
Immune reconstitution syndrome (IRIS) is reported in 16%-63% of HIV-infected patients with CMV retinitis following the initiation of HAART (median onset 43 weeks after starting HAART)
CMV IRIS manifest as painless floaters, blurred vision, photopia, decreased visual acuity, or ocular pain
Cytomegalovirus nephritis
CMV viremia has been associated with acute glomerular injury
Detecting CMV in the urine of a patient with renal failure does not meet diagnostic criteria for CMV nephritis (clinically inconsequential viruria)
Cytomegalovirus CNS disease
Association between CMV and Guillain-Barré Syndrome Younger patients (typically < 35 y) present with sensory defects and facial palsy, antiganglioside (GM2) IgM response, and mild long-term sequelae
CMV workup
IgM level is elevated in patients with recent CMV infection, or there is a 4-fold increase in IgG titers
False-positive CMV IgM results may be seen in patients with EBV or HHV-6 infections, RF
Anti-CMV immediate early antigen monoclonal antibody test, reacts with an early protein; can detect CMV infection 3 hours into the infection
Detection of the CMV pp65 antigen in leukocytes, expressed only during viral replication, immunofluorescence assay or mRNA amplification
Cytopathology
CMV treatment
Best options for treatment and prevention of cytomegalovirus (CMV) disease remain ganciclovir and valganciclovir 2nd line (foscarnet or cidofovir) or are used off-label (leflunomide)
Epstein-Barr Virus
EBV is transmitted via intimate contact with body secretions, primarily oropharyngeal secretions
EBV infects the B cells in the oropharyngeal epithelium
Symptomatic EBV
Fatigue may be profound initially following 1-2 month incubation
Gradually resolves with in 3 months
Some have initial recovery then prolonged fatigue without the features of infectious mononucleosis
Airway obstruction and central nervous system (CNS) mononucleosis are also responsible for increased morbidity
Presentation of EBV
triad of fever, pharyngitis, and lymphadenopathy
Hoaglund sign - bilateral upper-lid edema, last only a few days
EBV workup
Heterophile antibody test
Peak levels 2-6 weeks after primary EBV infection; may remain positive up to a year
Latex agglutination assay (using horse RBCs) has sensitivity is 85%; specificity is 100%
Heterophile antibody test (e.g. Monospot test) often negative early; increasing during 1st 6 weeks, if remains negative considered ‘heterophile-negative infectious mononucleosis’
EBV Treatment
Short courses of corticosteroids (7-10 days) are indicated for EBV infectious mononucleosis with hemolytic anemia, thrombocytopenia, CNS involvement, or obstructive adenoid/tonsillar enlargement
Patients with EBV infectious mononucleosis who have positive throat cultures for group A streptococci should not be treated because this represents colonization (~30%) rather than infection
Amoxicillin treatment of group A streptococcal oropharyngeal colonization with EBV infectious mononucleosis may result in a maculopapular rash
Fatigue may take some time to resolve, and some patients may develop a state of chronic fatigue that is induced, but not caused by, EBV infectious mononucleosis
Erythema Infectiosum – 5th disease
Usually a benign childhood condition characterized by a classic slapped-cheek and subsequent lacy exanthem
Caused by human parvovirus (HPV) B19
Incubation period is usually 7-10 days
3 Phases of Erythema Infectiosum
Phase 1: A bright red, raised, slapped-cheek rash with circumoral pallor develops, sparing of nasolabial folds
Phase 2: Occurs 1-4 days later; erythematous maculopapular rash on proximal extremities (usually arms and extensor surfaces) and trunk, which fades into a classic lace-like reticular pattern; palms and soles usually spared
Phase 3: Recurrences of lacy rash for weeks or months (especially with exercise, irritation, or overheating of skin from bathing or sunlight)
Do not, diagnose in phase 1
Fetal hydops - 5th Disease
Fetal transmission with severe anemia and resultant congestive heart failure
Occurs <10% of primary maternal infections
½ of women of childbearing age are seropositive (immune and at no risk for the fetus)
Erythema infectiosum Prevention/Isolation
Children with erythema infectiosum are not infectious; may attend childcare or school
Routine exclusion of pregnant women from the workplace where erythema infectiosum is occurring is not recommended (due to high prevalence of human parvovirus B19 infection and low incidence of fetal effects)
Exposed pregnant women should consult their OB/GYN regarding immune status and f/u
Herpes Simplex Virus
Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2)
HSV-1 is traditionally associated with orofacial disease
HSV-2 is traditionally associated with genital disease;
Lesion location is not necessarily indicative of viral type
Up to 80% of herpes simplex infections are asymptomatic
HSV - Gingivostomatitis
Acute herpetic gingivostomatitis
Primary HSV-1 infection in children 6 mo to 5 yr
Adults may have acute gingivostomatitis (less severe; more symptomatic as a posterior pharyngitis)
Infected saliva from an adult or another child is the mode of infection
Incubation period is 3-6 days
Clinical Features of HSV - Gingivostomatitis
Abrupt onset
High temperature (102-104°F)
Anorexia and listlessness
Gingivitis(most striking feature, with markedly swollen, erythematous, friable gums)
Vesicular lesions (develop on the oral mucosa, tongue, and lips and later rupture and coalesce
HSV Workup
Herpes simplex virus (HSV) infection is best confirmed by isolation of the virus in tissue culture
PCR has been used to detect HSV-2 as the cause of recurrent meningitis
HSV - Complications
Bacterial and fungal superinfections balanitiscan occur in an uncircumcised male due to bacterial infection of the herpetic ulcers
Candidalvaginitisin as many as 10% of women with primary genital herpes, particularly in women with diabetes, mucosal herpetic lesions can be confused withyeast infection
Ocular infections is not uncommon in children as a result of autoinoculation during acute herpetic gingivostomatosis or asymptomatic oropharyngeal HSV infection
HSV Treatment
Penciclovir (Denavir) - Inhibitor of DNA polymerase in HSV-1 and HSV-2 strains, inhibiting viral replication
Acyclovir (Zovirax) - Synthetic purine nucleoside analogue with activity against a number of herpesviruses,
HIV
Human immunodeficiency virus (HIV) is a blood-borne, sexually transmissible virus
Typically transmitted via
Sexual intercourse
Shared intravenous drug paraphernalia
Mother-to-child transmission (MTCT), which can occur during the birth process or during breastfeeding
Where the 2 types of HIV come from?
HIV-1 probably originated from one or more cross-species transfers from chimpanzees in central Africa
HIV-2 is closely related to viruses that infect sooty mangabeys in western Africa
HIV risk Factors
Unprotected sexual intercourse, especially receptive anal intercourse (8-fold higher risk of transmission)
Large number of sexual partners
Prior or current STDs
Gonorrhea and chlamydia infections increase the HIV transmission risk 3-fold
Syphilis raises the transmission risk 7-fold
Herpes genitalis raises the transmission risk up to 25-fold during an outbreak
Sharing of intravenous drug paraphernalia
Receipt of blood products (before 1985 in the US)
Mucosal contact with infected blood or needle-stick injuries
Maternal HIV infection
HIV Presentation
Acute seroconversion manifests as a flulike illness, consisting of fever, malaise, and a generalized rash
Asymptomatic phase is generally benign (aka asymptomatic)
Generalized lymphadenopathy is common ; may be a presenting symptom
Weight loss
HIV Workup
high-sensitivity enzyme-linked immunoabsorbent assay (ELISA) should be used for screening
CD4 T-cell count is a reliable indicator of the current risk of acquiring opportunistic infections
Newly diagnosed HIV infection workup to include the following?
Cytomegalovirus (CMV) testing
Syphilis testing
Rapid amplification testing for gonococcal and chlamydial infection
Hepatitis A, B, and C serology
Anti-Toxoplasmaantibody
Ophthalmologic examination
A purified protein derivative skin test (PPD) to evaluate for tuberculosis infection
Chest radiography should be performed in patients with a positive PPD test result
HIV Staging
Category A - asymptomatic HIV infection without a history of symptoms or AIDS-defining conditions
Category B - HIV infection with symptoms that are directly attributable to HIV infection
Category C - HIV infection with AIDS-defining opportunistic infections (previous slide with opportunistic infections
3 categories are further subdivided based on the CD4+T-cell count
Categories A1, B1, and C1 - CD4+T-cell counts > 500/µL
Categories A2, B2, and C2 - CD4+T-cell counts 200/µL - 400/µL
A3, B3 and C3 - CD4+T-cell counts < 200/µL
HIV Treatment
Efavirenz/tenofovir/emtricitabine (EFV/TDF/FTC)
Ritonavir-boosted atazanavir + tenofovir/emtricitabine (ATV/r + TDF/FTC)
Ritonavir-boosted darunavir + tenofovir/emtricitabine (DRV/r + TDF/FTC)
Raltegravir + tenofovir/emtricitabine
Antiretroviral regimen selection is individualized, on the basis of the following:
Virologic efficacy Toxicity Pill burden Dosing frequency Drug-drug interaction potential Drug resistance testing results Comorbid conditions
HIV Prognosis
Untreated HIV infection - overall mortality rate > 90%
Average time from infection to death is 8-10 years, although individual variability ranges from less than 1 year to long-term nonprogression
Variables implicated in HIV’s rate of progression, including CCR5-delta32 heterozygosity, mental health,concomitant drug or alcohol abuse, superinfection with another HIV strain, nutrition, age; also primary risk factor for initial infection
Prevention of HIV
Sexual transmission
Prevention measures include the following:
Abstinence when possible
Reduction in number of sexual partners
Using barrier contraception
Treatment of concurrent sexually transmitted diseases (STDs)
Testing of self and partner for HIV infection and other STDs
Vertical transmission
Prevention measures include the following:
Maternal testing
Effective control of maternal infection
Prenatal antiviral therapy and treatment of mother and infant during labor, delivery, and the neonatal period
Cesarean delivery
Avoidance of breastfeeding (unless local conditions make this unsafe or unfeasible)
Postexposure prophylaxis
HPV
Human papillomavirus (HPV) produces epithelial tumors of the skin and mucous membranes More than 100 HPV types are known HPV types 6 and 11 - low risk oncogenic potential; formation of condylomata and low-grade precancerous lesions HPV types 16 and 18 - high-risk types of HPV; responsible for most high-grade intraepithelial lesions that may progress to carcinomas
HPV Incidence
Anogenital HPV is the most common sexually transmitted infection in the US
Condylomata acuminata are clinically apparent in 1% of the sexually active population (molecular studies - 10-20% of men/women aged 15-49 yo HPV exposed)
Prevalence of 4-13% has been reported by sexually transmitted disease (STD) clinics
Common among adolescents and young adults
Estimated 80% of sexually active women will have been infected by age 50
Laryngeal Papillomatosis
An incubation period (latency period) is 3 months, but periods as long as 20 months
Age of onset usually 2-4 yo, but as late as juvenile onset documented, younger age worse prognosis
Symptoms include hoarseness, voice changes, croupy cough, stridor
Diagnosis by direct laryngoscopy
Prevention by HPV vaccine
Treatment by direct surgical resection (recurrences are the rule), tracheostomy occasionally required
Workup of HPV
Most diagnoses are made clinically
Exam of genital lesions with acetic acid helpful
Colposcopy & biopsy to determine extent of intraepithelial neoplasia
PAP Smear
HPV Treatment
No single curative treatment for condylomata acuminata
Treatment of most HPV infections involves agents that directly ablate the lesions
Medications used in treating HPV disease:
Immune response modifiers – imiquimod and interferon alfa and are primarily used in treatment of external anogenital warts or condylomata acuminata
Cytotoxic agents - antiproliferative drugs podofilox, podophyllin,
Influenza
Highly contagious airborne disease that causes an acute febrile illness (ranging from mild to respiratory failure/death)
Most significant immunologic surface proteins include hemagglutinin (H) and neuraminidase (N), which determine virulence
Influenza Presentation
Abrupt onset of illness is common (may be able to report the time when the illness began)
Fever may vary widely, 100-104°F; feeling feverish /chills
Sore throat may be severe and may last 3-5 days (often reason for office visit)
Frontal/retro-orbital headache is common; usually severe. (ocular symptoms photophobia, burning sensations, and/or pain upon motion
Ptosis is common
Complications of Influenza
Pneumoniain highest risk groups: women in the third trimester of pregnancy, elderly individuals, especially nursing home patients; those with cardiovascular disease usually constitute the highest risk group
Secondary bacterial pneumonia
Staphylococus aureus (most severe with cavitary infiltrates)
Haemophilus pneumonia
Steptococcus pneumoniae (S pneumoniae and H flu ususally develop
Methicillin-susceptibleS aureus (MSSA) and methicillin-resistantS aureus (MRSA) pneumonias, often severe & difficult to treat, fatal within 24 hours occasionally
Workup of Influenza
Viral culture of nasopharyngeal samples and/or throat samples
Rapid diagnostic tests are available, but because of cost, availability, and sensitivity issues, most flu is diagnosed clinically
PCR
Serologic Testing
Influenza Treatment
4 prescription antiviral drugs: oseltamivir, zanamivir, amantadine, rimantadine
Measles
one of the most contagious infectious diseases, at least a 90% secondary infection rate in susceptible domestic contacts
Measles is marked by prodromal fever, (3-Cs) cough, coryza, conjunctivitis
Transmitted via respiratory droplets, which can remain active and contagious, either airborne or on surfaces, for up to 2 hours
Measles Prognosis
Morbidity and mortality increased Immune deficiency disorders Malnutrition Vitamin A deficiency Inadequate vaccination (60-fold increase in risk of disease due to exposure to imported measles cases)
Measles Presentation
Incubation period 10-12 days
1st sign usually a high fever often >104 lasting 4-7 days
Prodromal phase associated with malaise, fever, anorexia,
classic triad (the ‘3-Cs’):
Conjunctivitis
Cough (may be the final symptom to appear though)
Coryza
Measles Complications
otitis media, interstitial pneumonitis, bronchopneumonia, laryngotracheobronchitis(ie, croup), exacerbation of tuberculosis
acute encephalitis
Measles Workup
Serologic testing for IgG (4 fold increase acute-convalescent serum) and IgM (positive by 3rd day of rash for 30-60 days)
Isolation of the virus
Reverse-transcriptase polymerase chain reaction (RT-PCR)
CBC may reveal leukopenia with a relative lymphocytosis and thrombocytopenia
LFTs results may reveal elevated transaminase levels in patients with measles hepatitis
CXR if pneumonia suspected
Measles Treatment
Supportive, IV hydration
Vitamin A – reduces severity & duration 50%
Postexposure prophylaxis should be considered in unvaccinated contacts
Antibiotic treatment of 2nd infections, e.g. pneumonia & otitis media
Ribavirin (IV or aerosolized) - treat severely affected and immunocompromised adults with SSPE, no controlled studies
MMR - preventive if administered within 3 days of exposure, contraindicated in HIV with CD4 count < 15%
Human Ig within 6 days of exposure
Molluscum contagiosum
MC virus causes a benign viral infection almost exclusively limited to humans
Papules are umbilicated and contain a caseous plug
3 Types of people affected by Molluscum contagiosum
Children - most common, become infected through direct skin-to-skin contact or indirect skin contact with fomites, e.g. bath towels, sponges, and gymnasium equipment
Immunocompetent adults - sexually transmitted disease (STD); few lesions limited to the perineum, genitalia, lower abdomen, or buttocks
Immunocompromised children or adults - widespread, persistent, and atypical molluscum contagiosum in those with AIDS with low CD4 counts
3 Types of molluscum contagiosum virus
Orthopoxvirus- resembles variola (smallpox) and vaccinia
Parapoxvirus- orf and milker’s nodule viruses
Unclassified (with features that are intermediate between those of the orthopox and parapox groups)
Distribution of molluscum contagiosum
Face, trunk, and extremities is observed in children; relatively common in the groin, perineal or genital (not pathognomonic of abuse)
Groin and genitalia in adults
Lesions are seldom found on the palms, soles, oral mucosa, or conjunctiva
Molluscum contagiosum Treatment
Spontaneous resolution generally occurs by 18 months in immunocompetent individuals; may persist up to 5 years
Treatment options:
Benign neglect - primum non nocere(first do no harm)
Direct trauma to lesions: acids, cryotherapy, pulse laser
Antiviral therapy
Immune response stimulation
Mumps
Mumps is an acute, self-limited, systemic viral illness characterized by the swelling of one or more of the salivary glands, typically the parotid glands RNA virus Salivary glands (also pancreas, testes) show edema and desquamation of necrotic epithelial cells lining the ducts
Prognosis and Complications of Mumps
Overall prognosis in uncomplicated mumps is excellent
Encephalitis:
Rates of mumps encephalitis 5:1000 reported mumps cases
Sensorineural deafness
Orchitis (usually unilateral)
Oophoritis
Pancreatitis
Treatment of Mumps
Supportive care
Reduce acidic foods, both salivary gland & gastric issues
Ice packs to parotid gland; ice/scrotal support for orchitis
Analgesic/antipyretics
Isolation for 5 days
Vaccine coverage
Rabies
viral disease that affects the CNS, single stranded RNA
Transmitted in saliva or in aerosolized secretions from infected animals, typically via a bite
2 Periods of Rabies
Incubation period
Asymptomatic; average duration is 20-90 days, usually < 1 year; but up to 7-19 years.
Incubation period < 50 days more likely if the patient is bitten on the head or neck or if a heavy inoculum is transferred through multiple bites, deep wounds, or large wounds
Rabies virus is segregated from the immune system ; no antibody response
Prodromal period
Virus enters the CNS; duration 2-10 days
Paresthesia, pain, intense itching at inoculation site is pathognomonic for rabies, may be only presenting sign; occurs in 50%
Acute neurologic period
Duration 2-7 days
Objective signs of developing CNS disease: muscle fasciculations, priapism, and focal or generalized convulsions
Patients may die immediately or may progress to paralysis, 1st in bitten limb at first but usually becomes diffuse
Furious rabies:
Agitation, hyperactivity, restlessness, thrashing, biting, confusion, or hallucinations lasting < 5 minutes; becomes episodic and interspersed with calm, cooperative, lucid periods
Episodes may be triggered by visual, auditory, or tactile stimuli or spontaneous; seizures may occur
Hydrophobia/aerophobia present in 50%; larynogospasm / diaphragmatic spasms with drinking water or air blown in face
May end in cardiorespiratory arrest or may progress to paralysis
Paralytic rabies (dumb rabies or apathetic rabies)
Relatively quiet; 20 % do not develop the furious form
Paralysis occurs from the outset
Coma
Rabies Postexposure
Rabies vaccine IM (deltoid) - 1 mL on days on days 0, 3, 7, and 14 (if immunocompromised, add an additional dose: 1 mL IM deltoid on days 0, 3, 7, 14, and 28)
Rabies immunoglobulin - 20 IU/kg infiltrated as much as feasible around and under the bite wound; if any left over, give IM (gluteus)
HRIG may be administered as long as 7 days after the first dose of vaccine (if not immediately available )
Prophylaxis may be discontinued if the animal does not develop rabies within 10 days or is found to be free of rabies upon sacrifice
Pregnancy is not a contraindication to postexposure prophylaxis against rabies
Roseola
human herpesvirus 6 (HHV-6)
Replication of the virus occurs in the leukocytes and the salivary glands
Classic presentation of roseola infantum is 9-12 mo infant with acute onset high fever; commonly a febrile seizure; 72 hours later rapid defervescence with onset morbilliform rash (early invasion of the CNS may occur)
HHV-6 then remains latent (like other herpes viruses) in most patients who are immunocompetent
Roseola Presentation
Acute onset of fever
Febrile seizure in 15%
Lack ofURI or GI symptoms, playful despite fevers of 104-105
After acute defervescence, exanthem: generalized but subtle with either discrete, small, pale pink papules or blanchable, maculopapular
Rubella Epidemiology
Young children - mild constitutional symptoms, rash, and suboccipital adenopathy
Older children, adolescents, and adults, rubella may be complicated by arthralgia, arthritis, and thrombocytopenic purpura
Rare cases occur of rubella encephalitis
Pregnant women
Presentation of Rubella
Incubation is usually 14-21 days after exposure to a person with rubella Conjunctivitis Sore throat Headache General body aches Low-grade fever Chills Anorexia Nausea Forchheimer sign
Congenital Rubella Presentation
classic triad of congenital rubella syndrome consists of:
Sensorineural hearing loss
Congenital heart disease
Ocular abnormalities including cataract, infantile glaucoma, and pigmentary retinopathy
Rubella Workup
Congenital rubella syndrome should be strongly suspected in infants > 3 mo if rubella-specific IgG antibody levels are observed and do not decline at the rate expected from passive transfer of maternal antibody (i.e. equivalent of a 2-fold decline in HI titer per mo)
Rubella-specific immunoglobulin M (IgM) antibody in a single serum sample
Rubella-specific IgG rise
Varicella Pathophysiology
Inhalation of contaminated respiratory droplets, the virus infects the conjunctivae or the mucosae of the upper respiratory tract
Viral proliferation occurs in regional lymph nodes of the upper respiratory tract 2-4 days after initial infection
Varicella Presentation
Incubation period of 10-21 days
Not heralded by a prodrome
Begins with the onset of an exanthem, infectious 1-2 days prior to rash developing
Small, erythematous macules appear on the scalp to face to trunk to limbs
Rapid sequential progression over 12-14 hours to papules to clear vesicles to pustules, which umbilicate and crust
Intense pruritus typical with vesicles
Remains infectious for 4-5 days after the rash develops, as last vesicle crusts over
Varicella Complications
Secondary bacterial infection
2nd bacterial infection of skin lesions most common complication - impetigo,cellulitis, anderysipelas
Staphylococci & streptococci most common bacteria
Disseminated primary varicella infection
Disseminated primary varicella infection seen in immunocompromised or adult populations,
CNS complications Reye syndrome – associated with ASA Guillain-Barré syndrome – ascending paralysis Acute cerebellar ataxia (post-varicella) Encephalitis
Hemorrhagic complications
Varicella Workup
Tzanck smear of vesicular fluid - multinucleated giant cells and epithelial cells with eosinophilic intranuclear inclusion bodies
Vesicular fluid culture – 40% sensitivity, better with direct immunofluorescence & PCR
Serologic testing – multiple tests for IgG
Chest radiography – signs of pneumonia
Histologic examination – nonspecific with herpes
Varicella Treatment
Clip nails
Antihistamines
Topical & parenteral antibiotics if 2nd infections
Acyclovir if risk for severe disease
