Viral Disease and Perinatal Transmission 11-20-23 (Student) (2).pptx

Viral disease and perinatal transmission of viral disease Sachi Patel, PA-C, MSPAS Assistant Professor, Master of Physician Assistant Studies November 2023 • Influenza • Measles  Congenital • Mumps • Epstein Barr Virus (EBV) • Rubella • Infectious Mononucleosis • German measles • Congenital...

Viral disease and perinatal transmission of viral disease Sachi Patel, PA-C, MSPAS Assistant Professor, Master of Physician Assistant Studies November 2023 • Influenza • Measles  Congenital • Mumps • Epstein Barr Virus (EBV) • Rubella • Infectious Mononucleosis • German measles • Congenital measles Plan • Varicella- Zoster Simplex • Cytomegalovirus • Roseola • Human Papilloma Virus (HPV) • Erythema infectiosum • Zika • Rabies • Monkey Pox • Herpes Simplex Virus • Polio • Type 1 • Type 2 (New PANCE addition for 2025) • Covid-19 Influenza • Acute respiratory illness caused by orthomyxovirus • Highly contagious and readily transmitted through droplet nuclei. • Causes Upper and lower respiratory infections • Most epidemics occur during the fall and winter • 3 strains exist (A, B, and C) and types are based on the surface antigens hemagglutinin (H) and neuraminidase (N) Influenza • Eg H1N1, • Eg H5N1 (Bird flu) (2009) • A infects birds, pigs, horses and humans • B and C primarily infects humans • Major mutations cause antigenic shifts, minor mutations cause antigenic drifts • Influenza in North America is most commonly caused by Type A and B • Associated with significant morbidity and mortality • Transmission via aerosols generated by coughs / sneezes InfluenzaPathophysiology • Virus replicates within 4-6 hours, then releases to infect nearby cells • Incubation period of 18-72 hours • Viral shedding stops 2-5 days after symptoms appear • Influenza A causes most severe & extensive outbreaks • Symptoms start usually 1-3 days after exposure • Abrupt onset of fever and cough InfluenzaSigns and Symptoms • Chills, malaise, muscle aches, substernal chest pian, headache, nasal stuffiness, and occasionally nausea • Fever lasts 1-7 days accompanied by coryza, nonproductive cough, photophobia, eye pain, sore throat, pharyngeal infection, and flushed face • Wheezing and rhonchi may be heard • Children may develop diarrhea • Affecting extremes of age and chronically ill • Necrosis of respiratory epithelium can result in secondary bacterial infection, acute sinusitis, otitis media, and purulent bronchitis • Influenza causes the respiratory track epithelium to break down. • Guillain Barre Syndrome InfluenzaComplication s • Myocarditis • Reye syndrome • Fatty liver with encephalopathy • Rapidly progressive with 30% fatality rate • May develop 2-3 weeks after the onset of influenza A or varicella infection especially if aspirin is ingested • Peak age is 15-14 year • Rarely occurs in adults • Vomiting, lethargy, jaundice, seizures, hypoglycemia, increased liver enzymes, ammonia levels, prolonged prothrombin time, change in mental status • Treatment is supportive Source: Pathology: Clinicopathologic Foundations of Medicine, 7e, 2014 InfluenzaDiagnostic Studies • Rapid antigen test-takes 15 mins • Sensitivity 50-70%, Specificity 90-95% • Results are most accurate during the first few days of illness • Can give false positives • Gold Standard: Viral cultures may take 2-5 days to return • Direct and indirect immunofluorescence assays 2-4 hrs • Nucleic acid amplification tests – PCR – 48 – 96 hrs. • Labs: Leukopenia and proteinuria may be present • CXR: May show bilateral diffuse infiltrates in primary influenza pneumonia • Supportive care • Rest, analgesics, cough suppressants • Prognosis generally good in uncomplicated cases without pneumonia • Patient generally recover 1-7 days • Antivirals: • Neuraminidase inhibitors Influenza Treatment • inhaled zanamivir [Relenza] or • oral oseltamivir [Tamiflu] • May help reduce severity of illness if administered within 48 hours of the onset of symptoms. • Effective against influenza A and influenza B • Contraindicated in patients less than 12 years old. • Fewer side effects as compared to M2 inhibitors • M2 inhibitors: • Amantadine (Symmetrel) • Rimantadine (Flumadine) • Recommended for patients with influenza requiring hospitalization or in patients with high risk of morbidity/mortality • As the prevalence of resistance to oseltamivir is on the rise, recommendation is to use zanamivir or combination of oseltamivir and rimantadine if influenza A is suspected or confirmed • Annual influenza vaccine proven to decrease mortality and morbidity from the flu • Immunity is set within 2 weeks of the vaccination • Configured based on the strains isolated during the preceding year Influenza Prevention • Contraindicated in patients with • hypersensitivity to eggs, • active acute febrile illness, or • in cases of thrombocytopenia • FluMist (live, attenuated virus) cannot be given to individuals who are immunocompromised  Everyone age 6mo and older* and those at greatest risk are recommended vaccination Measles Rubeola Measles (Rubeola) • Morbillivirus in paramyxovirus family • Incubation period is 8-14 days • Prodrome is generally fever, cough, anorexia, coryza, conjunctivitis for 1-3 days • Koplik spots in the mouth  "Salt crystals in their buccal mucosa" • Rash of maculopapular face to extremities • Treatment: • Supportive Source:Schaechter's Mechanisms of Microbial Disease, 6e, 2022 Mumps Parotitis Mumps • Paramyxovirus • Viral spread by respiratory droplets • In pre-vaccine period, mumps was the most common cause of viral encephalitis • Incubation 14-21 days • 1/3 of infections are subclinical • Signs and symptoms: • Pain and swelling of the salivary glands (in front and below the ear) • primary parotid glands • May also affect the pancreas, CNS, and testes • Orchitis may cause sterility • Individuals who had the disease develop lifelong immunity • Treatment: • Supportive Source: CDC.gov Rubella German Measles Congenital Rubella Rubella (German Measles) • Rubivirus • Mostly benign and self limiting • Signs and symptoms: • Non-specific respiratory symptoms • Maculopapular erythematous rash starting on face and progresssing to toes • Treatment: • Supportive Image sources Congenital Rubella • Most commonly noted in immigrant mom’s that are not immunized. • Can cause miscarriage, fetal death or congenital abnormalities • Smaller in size for age • Jaundice • Hearing loss • Cataracts • Congenital heart disease (PDA) • Purpuric rash (blueberry muffin) • Microphthalmia • MMR(now V) Vaccine • Live, attenuated strains of measles, mumps and rubella viruses (and varicella) • Given at age 12-15mo then 4-6 years • HUGE problem in certain cultural/religious groups • Outbreaks of these diseases are popping up all over • No link between vaccine and autism – FALSIFIED RESEARCH!!! • Congenital Rubella is Teratogenic Source: CDC.gov Roseola Roseola Infantum Roseola (Roseola Infantum, Exanthem Subitum) • Human herpes virus 6 or 7 • Incubation period is 10-14 days • Seen between the age of 6mo-3 years • Benign and self limiting • Signs and Symptoms: • Acute onset of High Fever for 4 days • Prodrome is a 4 day fever before the rash develops • Febrile seizures can occur 10% of the time • Pink macular rash appears after fever resolves • Maculopapular rash • Treatment: • Supportive Source:Lippincott's Illustrated Reviews: Microbiology, 3e, 2012 Erythema Infectiosum (Fifth Disease) Erythema infectiosum (Fifth disease, slapped cheek) • Caused by Human parvovirus B19 • Most common in school aged children • Incubation period is 4-14 days • Transmission via respiratory droplets • Can cause hydrops fetalis in pregnant • Generally, no prodrome • Red face “slapped cheek”, lacy pink macular rash on torso Source: Typical “slapped cheek” appearance of a child infected with parvovirus B19 (“fifth disease”).  Prodromal phase: Signs and symptoms + Treatment  Low grade fever, headache, URI sxs  Rash:  Facial flushing “slapped cheek appearance”  Lacy, pink macular rash on torso and extremities  Self-limiting and benign, supportive tx  Recommend to avoid contact with pregnant women to decrease fetal complications of anemia and miscarriage Rabies Rabies • Caused by the Rhabdovirus • Transmission: • via infected saliva from a virus carrying animal • Through bite wounds from bats, skunks, foxes, raccoons in US • Dogs and cats in developing countries. • Rodents and rabbits do not transmit rabies • Incubation period between the bite and onset of symptoms is 10 days to 7 weeks • Correlation between the period of incubation and the distance of the wound from the brain Source: Lippincott Illustrated Reviews: Integrated Systems, 1e, 2016 • Pain and paresthesia at the bite site RabiesSymptoms • Restlessness with muscle spasms and extreme excitability, bizarre behavior, convulsions, thick, tenacious saliva, hallucinations, insomnia • Hydrophobia • Patients may exhibit an ascending paralysis • Suspected animals are euthanized so brains can be tested for rabies using fluorescent antibody markers RabiesDiagnosis • Domestic animals may be quarantined and observed • PCR tests for humans may be negative in early disease • CSF may show rabies reverse transcriptase by PCR • MRI may reveal non-enhancing, ill defined changes in the brain steam, subcortical matter, or hypothalamus • PREVENTION IS KEY! • Post animal bite, clean and debride the wound IMMEDIATELY! • Wounds should not be sutured • Post exposure RabiesTreatment • Rabies immunoglobulin --in the wound and IM at a distant site • Human diploid cell vaccine (HDCV) • 5 injections of 1mL IM are administered on days 0,3,7,14, and 28 • If the patient received active immunization in the past, • immunoglobulin is not given, • HDCV doses are administered on days 0 and 3 only • If rabies develops, no treatment currently available • Fatal within 7 days, most commonly from respiratory failure • Rabies vaccine immunoglobulin + monoclonal antibodies, ribavirin, interferon-a, and ketamine should be provided • Mechanical ventilation and oxygen therapy as needed • Control of bat population • All household pets should eb immunized • Those who regularly handle pets must receive active immunization RabiesPrevention • Preexposure vaccination of those at high risk is accomplished with IM HDCV doses on days 0,7, and either 21 or 28. • HDCV can also be administered intradermally on days 0,7, and 28 • Rabies antibody titers should be checked every 2 years, boosters are administered to persons who become seronegative Human Herpesviruses 8 identified HHV 1. HSV-1 2. HSV-2 3. VZV 4. EBV • Infectious mononucleosis (Type-4) 5. Cytomegalovirus 6. Causative agent of Exanthema Subitum (Roseola) 7. Herpes Virus 7 causative agent of roseola seizure 8. Herpes Virus 8 causative agent of Kaposi sarcoma Herpes Simplex Virus • Transmission by close contact and inoculation of the virus into the mucosal surface or through abrasions in the skin • HSV type 1 • HSV type 2 Herpes simplex virus (HSV) • HSV remains latent in varying dorsal root ganglia • Reactivation may be precipitated be fever, stress, menses, trauma, UV light, weight gain or loss, immunosuppression, or other factors. • Reactivation is more frequent and more severe in patients who are immunocompromised. • The most common viral etiology of Bell's palsy Modified from Figures 25.4, 25.11, and 25.25, Harvey RA, Cornelissen CN. LIR Microbiology, 3rd ed. Baltimore, MD: Lippincott Williams & Wilkins, 2013 . Photo A from Bernard A. Cohen, MD, Christoph U, Lehman, MD, DermAtlas, Johns Hopkins University. Photo B is from Habif, T. P. Clinical Dermatology, A Color Guide to Diagnosis and Therapy. St. Louis: Mosby, 1996. Fig. 12–34, p. 345 . Primary and Recurrent HSV infection • Lesions begin as erythematous papules that rapidly develop into tiny, thin-walled, grouped vesicles • The vesicles continue to erupt over 1-2 weeks • Recurrence is heralded by burning or stinging • Neuralgia may occur • Constitutional symptoms are unlikely Source: Lippincott® Illustrated Reviews: Microbiology, 4e, 2020 • Asymptomatic shedding of either virus is common • Primarily affect the oral and genital areas Herpes simplex virus (HSV) • • • • • • • • Mucocutaneous disease Ocular disease Neonatal and congenital infection Central nervous system disease Disseminated disease Bell palsy- association with HSV-1 is established Esophagitis and proctitis Erythema multiforme • Principal symptom are burning and stinging • Lesions consist of small, grouped vesicles on erythematous base that can occur anywhere most common: HSV Type 1 and 2 • • • • • Vermilion border Penile shaft Labia Perianal skin Buttocks • Regional lymph nodes may be swollen and tender • Lesions usually crust and heal in 1 week Acute herpetic gingivostomatitis HSV 1 • Most common orolabial area • Over 85% of adults have serologic evidence of HSV-1 infections HSV type 1&2 • Usually asymptomatic as a child • Recurrent, self-limited attacks are common • Average of two attacks per year • Maximum shedding in the first 24 hours of each outbreak • Number of outbreaks decrease with time • Has a predilection for the trigeminal nerve HSV 2 • Most common in genital area. The virus typically causes genital lesions • About 25% of the US population have serologic evidence of infection with HSV-2 • Transmission may be via sexual contact or during vaginal delivery • Asymptomatic shedding and painful eruptions can be frequent • 90% of cases can reactivate within 12 months. • More than 30% of patients have 6 episodes/year and about 20% have more than 10 episodes per year • Remains dormant in the sacral root ganglia Acute herpetic pharyngotonsillitis HSV-Type 1 • Common in adults manifesting initial HSV-1 disease and less common in those manifesting HSV-2 • Patients present with fever, malaise, headache, and sore throat • Vesicles are formed on the posterior pharynx and tonsils. • Vesicles rupture and form shallow ulcers • Grayish exudate may be present over the posterior mucosa Source:AAFP.org HSV Type 2 Source: Lippincott® Illustrated Reviews: Microbiology, 4e, 2020 Laboratory Findings • Diagnosis is generally clinical • Direct fluorescent antibody slide tests • Viral cultures of the vesicular fluids • Tzanck smear, immunofluorescent staining reveals multinucleated giant cells • Antibodies can be identified in the serum by PCR techniques Source: nlmn.nih.gov HSV 1 HSV type 1&2 TREATMENT • Oral antiviral cream • 5% Acyclovir • Penciclovir Cream applied every 2 hours while awake for 4 days • Potent topical corticosteroid 3x/d reduced duration, size and pain of orolabial herpes when added to oral antiviral agent HSV 2 • First Outbreak: • Acyclovir 400mg po 5x/d, or 800 mg TID • Valcyclovir 1000mg BID • Famciclovir 250mg TID • Treat for 7-10days • Subsequent Outbreaks: • Acyclovir 200mg 5x/d x 5 days • Valcyclovir 500mg BID x 3 days or 2g BID x 1 day • Famciclovir 125mg BID x 5days or 1 g once or twice/day Mucocutaneous Disease • HSV-1 • Herpes labialis or gingivostomatitis • Herpetic whitlow: digital lesions • Herpes gladiatorum: skin infection • HSV-2 • Largely involve genital tract: lesions remain dormant in presacral ganglia • Occasionally lesions arise in perianal region or on buttocks and upper thigh Ocular Disease • HSV can cause keratitis, blepharitis and keratoconjunctivitis • Keratitis usually unilateral and is often associated with impaired vision • Lesions limited to epithelium usually heal without affecting vision • Stromal involvement can cause uveitis, scarring, and eventual blindness • PE: Keratitis- branching or dendrites that stain with fluorescein • Treatment: • topical antivirals…combination with interferon and debridement hastens healing; • acute retinal necrosis: IV acyclovir, oral famciclovir Neonatal and Congenital disease • Both HSV-1 and HSV-2 can affect the fetus and induce congenital malformation • Organomegaly • Bleeding • CNS abnormalities • Neonatal transmission during delivery is more common than intrauterine infection • Treatment: IV acyclovir 20mg/kg Q8 hrs for 14-21 days (for neonate), maternal antenatal suppressive therapy beginning at 36 weeks gestations decreases detectable HSV • C-section recommended for pregnant women with active lesions or prodromal symptoms TORCH complex • • • • • Toxoplasma Varicella zOster Rubella Cytomegalovirus Herpes simplex Source: Rubin's Pathology: Mechanisms of Human Disease, 8e, 2020 • Herpes simplex encephalitis • Predominantly caused by HSV-1 • Presents as nonspecific symptoms • Flu-like prodrome followed by headache, fever, behavioral and speech disturbances and focal or generalized seizures • Temporal lobe often involved CNS disease • HSV-1 and HSV-2 are recognized as a cause of mild, nonspecific neurologic symptoms and are also associated with benign recurrent lymphocytic (Mollart) meningitis • DX: HSV DNA PCR of cerebrospinal fluid is a rapid sensitive tool • Antibodies to HSV in cerebrospinal fluid can confirm diagnosis but happen later in disease • Treatment: IV acyclovir 10 mg/kg Q8 hr for 10 days or more Disseminated Disease Esophagitis & Proctitis •Occurs in setting of immunosuppression • Eczema herpeticum • Burns, atopic dermatitis, eczema, site long-term topical steroid use •Pneumonia can occur regardless of immune status • CT scan: diffuse or multifocal areas of ground-glass attenuation or consolidation changes • HSV-1 can cause esophagitis in immunocompromised patients • DX: endoscopic biopsy and culture • HSV-1 may also activate mononuclear cells in the pathogenesis of achalasia • Proctitis often occurs in men who have sex with men • Dx: rectal swab for PCR or culture, complicated cases require biopsy • TX: IV acyclovir or oral acyclovir Erythema Multiforme • Herpes simplex viruses remain a leading cause of erythema multiforme and Steven-Johnson syndrome • TX: suppressive therapy with oral acyclovir 400 mg BID x 6 months; valacyclovir 500 mg BID maybe effective in cases unresponsive to acyclovir Latex condom usage Patient education Sunscreen HSV-1 • Topical Therapy • 5% acyclovir ointment • Acyclovir 200 mg QID • Suppressive therapy HSV-2 • For frequent or severe recurrence: • Acyclovir 400 mg BID • Valcyclovir 500mg daily • Famciclovir 125-250 mg BID • • • • Prevention Varicella Zoster Viral infections Human Herpes Virus 3 • Highly contagious member of the herpesvirus Varicellazoster viral (VZV) infections • Primary infection • Varicella(Chickenpox) • Generally, presents during childhood • Most cases occur in the late winter or spring • Incubation period is 10-20 days • Most contagious 1 day before the rash appears • Spreads by inhalation of infective droplets or contact with lesions • Fever and malaise • Single attack confers lifelong immunity • Some cases may be life-threating in adults of immunocompromised adults VZV (Rash) • Generalized pruritic eruption that follows a centripetal pattern • Begin as erythematous macules and papules forming superficial vesicles (dew drops on a rose petal) that later crust over • Lesions appear in red clusters “crops”. Several morphologies can be indemnified • Rash prominently on the face, scalp, and trunk and later involves extremities • New lesions erupt for 1-5 days • The crusts slough in 7-14 days Source: Lippincott's Illustrated Reviews: Microbiology, 3e, 2012 • Mucous membranes can be involved • Systemic symptoms are variable • Severe, progressive infections manifest with deeper lesions in the lung, liver, pancreas, or brain. Mortality is 10% • Complications include secondary bacterial infections of excoriated lesions, varicella embryopathy, and Reye syndrome “dew drop on rose petal” appearance • Zoster (shingles) is the reactivation of varicella that has been dormant in ganglionic satellite cells • Latent VZV will reactivate as herpes zoster in about 10-30% of persons VZV reactivation (Zoster) • Outbreak may be precipitated by illness, stress or advancing age • More than half of all patients are >60y/o • Painful eruption usually following a dermatomal pattern • Thoracic and lumbar areas are most common Complications: •Herpes zoster ophthalmicus • • Lesion at tip of nose, inner corner of eye, and root and side of nose (Hutchinson sign) indicates involvement of trigeminal nerve Needs ophthalmic consult/evaluation •Herpes zoster oticus (Ramsey Hunt syndrome) • Facial palsy, lesions of external ear with or without tympanic membrane involvement, vertigo and tinnitus or deafness signify geniculate ganglion involvement Source: Lippincott's Illustrated Reviews: Microbiology, 3e, 2012 VZV Diagnosis • Clinically established • confirmation by direct immunofluorescent antibody staining or PCR of scrapings from lesions • Multinucleated giant cells are usually apparent in Tzanck smear • A varicella skin test and interferon-gamma enzyme-linked immunospot (ELISPOT) can screen for VZV susceptibility • Supportive care for symptom relief for itching isolation and hygiene recommendations. • Prevention of secondary bacterial infection is key VZV Treatment • Varicella • Immunocompromised patients exposed to varicella should receive acyclovir and varicella-zoster immunoglobulin • Acyclovir 20 mg/kg po QID x 5 days should be given within first 24 hours after onset of varicella rash (children older then 12 y/o) • Acyclovir 30mg/kg/d three divided doses for at least 7 days: immunocompromised pt, pregnant pt in third trimester, pt with extracutaneous disease • Herpes Zoster • Acyclovir 800 mg 5x day • Valcyclovir 1 g po TID x 7 days • Started within 72 hours of onset of lesion • IV acyclovir for extra dermatomal complications • Postherpetic neuralgia can be treated with a short course of steroids, tricyclic antidepressants, capsaicin cream, or gabapentin or pregabalin • VARICELLA • Live attenuated vaccine administered at 1-2 years of age for varicella • Quadrivalent measles, mumps, rubella and varicella (ProQuad) • First dose at 12-15 months and second dose at 4-6 years • Individuals older than 13 y/o two doses of single antigen 4-8 weeks apart • Postexposure: vaccine is recommended, or Varicella-zoster immunoglobin (VZIG) if can not get vaccine • Avoid the vaccine in pregnancy VZV Prevention • HERPES ZOSTER • CDC recommends two doses of recombinant zoster vaccine (RZV, Shingrix) to prevent shingles and related complications in adults 50 years and older. • Shingrix is also recommended for adults 19 years and older who have weakened immune systems because of disease or therapy. • Zostavax single dose for patients 60 years or older • Decreases shingles by 50% and reduces the risk of postherpetic neuralgia • Contraindicated in patients allergic to gelatin or neomycin, immunocompromised, untreated tuberculosis, or are pregnancy • Affected infants secondary to maternal varicella infection up to 20 weeks gestation • Low birth weight Congenital Varicella • Damage to nervous system during fetal development • Abnormalities of the skin, arms legs, hands and/or feet, cortical atrophy, ventriculomegaly • Occurs in 1-7/10,000 pregnancies • Severe, neonatal varicella is possible if congenital varicella syndrome that develops in the final days before birth Epstein Barr Virus Infectious Mononucleosis Human Herpes Virus 4  A human herpes virus 4  Most commonly transmitted via saliva but can be transmitted from genital secretions.  Infectious Mononucleosis "the kissing“ is a common manifestation of EBV Epstein-Barr Virus (EBV)  Infects >95% of adult population worldwide and persisting for the lifetime of the host. • Incubation period lasts several weeks (30-50 days) • EBV usually develops in persons between ages 10 and 35 y/o  Has been noted to increase risk of cancer  Burkitt lymphoma  Nasopharyngeal carcinoma  Pediatric leiomyomas  Collagen vascular diseases Role of EBV in infectious mono, nasopharyngeal carcinoma, and Burkitt lymphoma Source: Rubin's Pathology: Mechanisms of Human Disease, 8e, 2020  Splenomegaly in 50% of cases  Symptoms of fever, sore throat, Malaise, anorexia, myalgias  Lymph nodes enlarged (posterior cervical chain)  Nonsuppurative  Minimal pain  Conjunctival hemorrhage. Signs and symptoms  Oral lesions  Exudative pharyngitis  Tonsillitis  Gingivitis  Soft palate petechiae  Maculopapular or occasional petechia rash in 15%  Administration of amoxicillin raises incidence of rash to 90%  Hepatitis  Secondary bacterial pharyngitis  Most commonly Strep  Splenic rupture  Pericarditis Complication s  Myocarditis  Aseptic meningitis  Transverse myelitis  Encephalitis  LABS:  Increased hepatic aminotransferases (ALT/AST),  Increased bilirubin,  Decreased cryoglobulins EBVDiagnosis  Heterophil sheep cell agglutination (HA) antibody test or correlated mononucleosis spot test (Monospot)  Usually positive within 4 weeks  False positive VDRL or RPR in 10% of infected patients  During acute illness rise and fall in IgM antibody to EB virus capsid antigen (VCA) and a rise in IgG antibody to VCA, which persist for life • Antibodies (IgG) to EBV nuclear antigen (EBNA) appear after 4 weeks of onset and also persist • PCR for EBV DNA Source:Permission granted by WebPath, courtesy of Edward C. Klatt MD © 1994-2015 by Edward C. Klatt MD, Savannah, Georgia, USA.  Over 95% of patients with acute EBV-associated infectious mononucleosis recover without specific antiviral medication • In uncomplicated cases fever disappears in 10 days, lymphadenopathy and splenomegaly in 4 weeks • The debility may linger for 2-3 months • Hand-washing after contact and avoidance of close contact with acute cases is important • Avoid contact sports if splenomegaly EBVTreatment Tx options:  Symptomatic care with non-aspirin antipyretics and anti-inflammatories  Antivirals decrease shedding but do not affect the course of the illness  Steroids are indicated for thrombocytopenia, hemolytic anemia, or airway obstruction secondary to enlarged lymph nodes Cytomegalovirus Human Herpes Virus 5 CMV • Cytomegalovirus (CMV) • Most CMV infections are asymptomatic • After primary infection virus remains latent in most body cells • Transmission occurs through sexual contact, breastfeeding, blood products, transplantation, person-to-person, or congenital • Serious disease occurs primarily in immunocompromised persons • Three recognizable clinical syndromes • Perinatal disease and CMV inclusion disease, disease in immunocompetent persons, and disease in immunocompromised persons CMV PERINATAL & CMV INCLUSION DISEASE • Most common congenital infection in developed countries (0.2% and 2% of all live births) • Transmission is much higher from mothers with primary disease during pregnancy than those with reactivation (40% vs. 0.2-1.8%) • About 10% of infected newborns will be symptomatic with CMV inclusion disease • Jaundice, hepatosplenomegaly, thrombocytopenia, purpura, microcephaly, periventricular CNS calcifications, mental retardation, and motor disability • Perinatal infection acquired through breastfeeding or blood products typically shows a benign clinical course – not MCV inclusive disease Immunocompetent patients • Acute CMV infection is the most common cause of mononucleosis- like syndrome with negative heterophil antibodies • Fever, malaise, myalgias, arthralgias, and splenomegaly, cutaneous rash • Mean duration of symptoms is 7-8 weeks • Complications: mucosal gastrointestinal damage, encephalitis, severe hepatitis, thrombocytopenia, Guillain-Barre syndrome, pericarditis, myocarditis Immunocompro mised patients • Tissue and bone marrow transplant patients are mainly at risk for a year after allograft transplantation • HIV-infected patients occur most predominantly when CD4 count is <50 cells/mcL • CMV Retinitis- fundoscopic exam neovascular, proliferative lesions (“pizza pie” retinopathy) • Gastrointestinal and Hepatobiliary CMV • Respiratory CMV-cough, dyspnea and relatively little sputum production • Neurologic CMV- polyradiculopathy, transverse myelitis, ventriculoencephalitis, focal encephalitis • Mother and newborn Diagnosis • Pregnant women should be tested for IgM CMV antibodies every 3 months if + in first trimester • Congenital CMV disease is confirmed by presence of the virus in amniotic fluid or an IgM assay for fetal blood • PCR assay of blood or ELISA of urine during first 3 weeks of life • Immunocompetent persons • CMV specific IgM or four-fold increase of specific IgG levels support the diagnosis of acute infection • Immunocompromised persons • PCR analysis • Rapid shell-vial cultures detect early CMV antigens with fluorescent antibodies in 24-48 hours (bronchoalveolar lavage fluid) • Imaging • CMV pneumonitis are consistent with interstitial pneumonia (Xray) Diagnosis • Biopsy • Characteristic CMV histopathologic findings of intranuclear (“owl’s eye”) and intracytoplasmic inclusions Treatment • Sight-threatening retinitis • Ganciclovir induction therapy IV • Less severe retinal disease: Valganciclovir oral • HAART reduces need for CMV antiviral agents • Non-severe post transplant CMV disease • Oral valganciclovir 900mg BID • IV Ganciclovir 5mg/kg every 12 hours • Severe post transplant CMV disease • IV Ganciclovir remains the treatment of choice, treatment continued for at least 2 weeks until viral eradication is achieved Prevention • CMV glycoprotein B with MF59 adjuvant vaccine is currently under development • HAART is effective in preventing CMV infection in HIVinfected patients • Valganciclovir prophylaxis 450 mg po BID (high risk – stem cells, immunocompromised) • CMV immunoglobulin (ONLY in stem cell pts) Human Herpes Virus 6 • B cell lymphotropic virus • Two variants (A & B) • Principal cause of exanthema subitum (roseola infantum, sixth disease) • Occur most commonly in children under age 2 y/o • Also associated with encephalitis and acute liver failure Human Herpes Virus 7 • T cell lymphotropic virus • Associated with roseola, seizures and rarely encephalitis • Infection with HHV-7 is synergistic with CMV in kidney transplant recipients • Kaposi Sarcoma, multicentric Castleman disease, and primary effusion (body cavity) lymphoma • Infection is endemic in Africa Human Herpes Virus 8 • Kaposi Sarcoma: • Lesions may appear anywhere (even organ systems), careful exam of eyelids, conjunctiva, pinnae, palate and toe webs is important • Light-skinned individuals: purplish, non-blanching lesions can be papular or nodular • Dark-skinned individuals: lesions may appear more brown • Visceral disease (GI, pulmonary) will develop in 40% of patients with dermatologic Kaposi lesions • Treatment: Rapidly progressive dermatologic or visceral disease treated with chemotherapy. Milder forms usually improve with ART Copyrights apply Human Papilloma Virus Human Papillomavirus (HPV) • Transmission • Primarily by genital contact, usually (but not necessarily) through sexual intercourse • Epidemiology • Most common STI (CDC 2010) • About 6 mil new infections per year • About 1% of sexually active adults in US have genital warts at any one time • Subtypes 16,18,and 45 are typically correlated with cancers of the mouth and genitals  Common skin warts HPV     Most caused by HPV types 1-4 Typically asymptomatic Hands and feet are commonly affected Warts may be flat and superficial or plantar and deep • Laryngeal warts • Caused by serotype 11 • May be life threatening in children if they obstruct the airway • Must be removed surgically HPV  Anogenital warts (condyloma acuminata)  Occur in the squamous epithelium of the external genitalia and perianal area  Most commonly caused by types 6 and 11  Sexually transmitted  Condoms reduce transmission  Low Risk of neoplasia  Rarely turn cancerous unless the patient is immunosuppressed Rubin's Pathology: Mechanisms of Human Disease, 8 2020 HPV  Cervical/anal dysplasia  Most commonly HPV types 16,18, and 45 have been implicated in intraepithelial cervical dysplasia, neoplasia, and invasive carcinoma  High risk for neoplasia  Vaginal, anal, penile, head and neck cancer  Vaccination available against HPV  Approved for ages 9-26 Rubin’s Pathology: Clinicopathologic Foundations of Medicine, 7e, 2014  Histologic sampling- Biopsy with typing HPVDiagnosis  Hyperplastic prickle cells and excess keratin in skin warts  Koilocytotic or vacuolated squamous epithelium on pap smear results may represent cervical warts  Molecular DNA detects and types HPV on cervical swabs  Spontaneous treatment of skin warts are typical  Persistent lesions may be treated medically or surgically HPV treatment  Medical options:  salicylic acid  Podophyllum  topical interferon (imiquimod)  Surgical options:  blunt dissection  Electrocautery/Cryotherapy (liquid nitrogen)  Surgical excision  44.9% prevalence of prenatal transmission  Most transmission may occur at delivery  Transmission in utero is also possible Transmission of HPV  Very little is known about the effect of HPV on pregnancy outcomes  No clinical guidelines are in place to test donor sperm for HPV  Educate patients Zika • Transmitted by the Aedes mosquito • May also be transmitted to fetus sexually and by blood infusion • Most infections are asymptomatic • Fever, maculopapular rash, conjunctivitis, arthralgias, and headache are common Zika • Complications include neurologic disease and microcephaly, and fetal loss in pregnant women(congenital Zika infection) • Diagnosis by PCR testing for acute infection and virus serology • Treatment is symptomatic • Pregnant or individuals that wish to become pregnancy should avoid travel to zika-infected areas Zika Source: CDC.gov • Pregnant women should NOT travel to areas with Zika outbreaks ZikaPrevention • Before travel to other areas with risk of Zika, pregnant women and couples planning pregnancy in the next 3 months should discuss their travel plans with their health care provider and carefully consider the risks and possible consequences of travel to these areas. • All travelers to areas with risk of Zika should (1) prevent mosquito bites and (2) use condoms or not have sex for 2 months (for the partner that will be pregnant) -3 months (for the partner that will supply sperm) after the return or development of symptoms Monkey Pox  Rare disease cause by infection with the monkeypox virus.  Same family of viruses as Variola virus that causes Smallpox.  Monkey pox has similar sxs as smallpox but milder and rarely fatal.  Initially discovered in 1958 when two outbreaks of pox like disease noted in monkeys. Source of disease remains unknown (not from monkeys).  Prior to 2022 outbreak, monkeypox was reported in several central and western African countries. What is Monkey Pox?  Transmission:  Animal to human  Human to human  Close or Intimate contact  Direct contact with someone infected  Touching objects, fabrics and surfaces that have been used by infected person  Contact with respiratory secretions  Sexual intercourse or contact (Oral, Anal, Vaginal)  Hugging, prolonged Face-to-face contact Source CDC  Incubation period  Usually around 5-13 days People with monkeypox get a rash that may be located on or near the genitals (penis, testicles, labia, and vagina) or anus (butthole) and could be on other areas like the hands, feet, chest, face, or mouth. • The rash will go through several stages, including scabs, before healing. • The rash can initially look like pimples or blisters and may be painful or itchy. Typically 2-5mm diameter macules. Other symptoms of monkeypox can include: Signs and Symptoms • Fever • Chills • Swollen lymph nodes • Exhaustion • Muscle aches and backache • Headache • Respiratory symptoms (e.g. sore throat, nasal congestion, or cough) • Proctitis and tonsilitis were noted in the 2022 outbreak Source CDC Signs and Symptoms Source CDC How long do monkeypox symptoms last?  Monkeypox symptoms usually start within 3 weeks of exposure to the virus. If someone has flu-like symptoms, they will usually develop a rash 1-4 days later.  Monkeypox can be spread from the time symptoms start until the rash has healed, all scabs have fallen off, and a fresh layer of skin has formed. The illness typically lasts 2-4 weeks. Monkey Pox Pictures on CDC  Currently for the 2022 outbreak-- specimen sent for testing after consultation with public health authorities. Diagnosis  PCR test for orthopoxvirus: Sample the lesion on the skin or a throat swab.  Serologic testing: Antiorthopoxvirus IgM antibody detectable during the period of 5 days after rash onset. IgG detectable 8 days after onset of rasht  Electron microscopy  Histopathologic analysis. Source CDC Prevention Source CDC  JYNNEOS Vaccine is currently approved for prevention of small pox and monkeypox.  ACAM2000 vaccine is an alternative to JYNNEOS  Single dose  There are no treatments specifically for monkeypox. But because the viruses that cause monkeypox and smallpox are similar, antiviral drugs developed to protect against smallpox may be used to treat monkeypox effectively.  TPOXX (Tecovirimat) FDA approved for Small pox  Drugs developed to treat smallpox may be used to treat monkeypox. Treatment • Research is currently happening to test the safety and effectiveness for all people with monkeypox. • TPOXX is currently only for people with severe monkeypox disease or who are at high risk of severe disease, like people with weakened immune systems or skin conditions, such as HIV that is not virally suppressed and eczema. • TPOXX may help prevent or minimize severe monkeypox disease involving the eyes, mouth, throat, genitals, and anus (butthole). It may provide relief for short-term symptoms such as pain, swelling, and abscesses and longterm effects such as scarring. Source CDC Polio Newly added to the PANCE blueprint effective January 2025 Poliovirus infection primarily affects the musculoskeletal and neurologic systems leading to permanent paralytic disease. Brief info about the enteroviruses  Human are major natural hosts of Enteroviruses such as Poliovirus, Coxsackievirus, echoviruses What is Polio?  Coxsackie virus commonly causes hand, foot, mouth disease, conjunctivitis and other  Echoviruses causes viral meningitis  Poliovirus causes polio  NO evidence of disease spreading from animals to humans  Worldwide distribution  Enteroviruses are resistant to acid, detergents, and many disinfectants  Formaldehyde, hypochlorite active against enteroviruses Epidemiology of Polioviruses  Worldwide  Three poliovirus serotypes (type 1,2,3) Epidemiolog y  First emerged in the 19th century in developed temperate zone countries.  Mainly affects children <5yo  Risk of paralytic disease increases with age  Cases have decreased by >99% since 1988 to 2016 due to successful vaccination. However, noted to be on an increase since 2017-2022 in the endemic and underdeveloped countries of Asia, Africa and Middle east. Etiology  Spread via Direct or indirect fecal oral transmission is the most common Etiology  Person to person.  Respiratory secretions  Crosses the blood brain barrier leading to motor neuron cells being destroyed causing paralysis Clinical Signs and Sxs  Most infections (perhaps 80-90%) are either completely subclinical or so mild that they do not gather attention.  1 out of 4 experience flu-like sxs– sore throat, fever, tiredness, nausea, headache, stomach pain.  Incubation period : Range can be 4-35 days but usually between 7-14 days.  3 types of disease can be observed.  Abortive poliomyelitis :  Most common  non-specific febrile illness of 2-3 days with  no CNS sxs  Aseptic meningitis: (non paralytical poliomyelitis) characterized by signs of meningeal irritation Clinical Signs and Sxs  Stiff neck, pain and stiff back  Along with flu like sxs  Sxs resolve within a few days  Paralytic poliomyelitis     Usually <2% of infections Brief period of minor illness Signs of meningeal irritation Hallmark sign is paralytic poliomyelitis (Asymmetric flaccid paralysis without sensory loss.  Extent of involvement differs from case to case. Worse involvement is all 4 limbs paralyzed or brain stem is attacked  Max extent of effect is noted in first few days. Thereafter, temporarily damaged neurons regain their function and recovery begins  Recovery of function can take upto 6 months, after this time the persistent paralysis is permanent Treatment  Supportive treatment w/ pain management and PT  No approved antiviral therapies for poliomyelitis Treatment  Symptomatic treatment for fever and flu-like sxs.  Respiratory failure will require mechanical ventilation.  Close monitoring of CV status due to BP fluctuations and autonomic dysfunction with CNS involvement.  2 types of poliovirus vaccines:  Inactivated or killed polio vaccine (IPV)  Currently used in US  Live, attenuated virus, oral polio vaccine (OPV)  Mostly used in developing countries  Each type contains all 3 poliovirus serotypes. Prevention  Use of IPV has dramatically decreased paralytic cases since 1955.  Sub Q injection  4 doses: At ages 2 mo, 4mo, between 6-18 months, between 4-6 years  IgG antibodies produced in 98% of recipients.  Considered safe and w/o significant deleterious side effects. Prevention Sars COVID-19 What is COVID-19  Severe acute respiratory syndrome coronavirus 2 (SARSCOV-2, COVID-19)  β-coronavirus that gains entry into the cell through angiotensinconverting enzyme 2 (ACE2)  COVID-19 was first identified through a cluster of cases in Wuhan, China, in late 2019 and spread rapidly to pandemic status. Epidemiolog y + Etiology  Transmission:  Direct person-to-person contact primary route of transmission.  Touching contaminated surfaces then touching ones own eyes, nose or mouth  Longer distance transmission suspected due to large outbreaks  Time of contagion is 7-10 days.  Transmission after 10 days less likely.  Risk of transmission depends on exposure type:  Risk of transmission from an asymptomatic person is less.  Risk increases with closeness and duration of contact  Higher with prolonged indoor settings Risk Factors for severe disease  Diabetes  Cerebrovascular disease  CKD  Down syndrome  COPD  HIV  Obesity  Neurologic disorders  Heart disease  Pregnancy  Sickle cell dz, thalassemia  Sickle cell disease  Cancer  Tobacco use, substance abuse disorders  Use of corticosteroids or other immunosuppressives  Cystic fibrosis  History of transplantation: solid organ, stem cell  Case reports have shown exposure up to 6-7 days prior to onset of symptoms…this is thought to be the period of highest infectiousness up to 2 days after the onset of symptoms  Viral RNA may still be detectable more than 10 days after onset of symptoms….however, in mild to moderate case it is thought the RNA levels are to poor replication capability…. Clinical manifestation  Asymptomatic transmission:  Known to occur is as much as 6-7 days prior to infection  Has been proven to be the cause of many outbreaks *Children under 5yrs of age may have up to 100X virus in the upper respiratory tract  Initial Presentation in most of the cases (97%)  Cough  Fever  Dyspnea  Initial Presentation in most of the cases (97%)  Cough  Fever  Dyspnea Clinical manifestation  Other sxs:  Myalgias  Headache  Sore throat  Rash  Diarrhea  Nausea/ Vomiting  Loss of taste or smell  Abdominal pain  Rhinorrhea  Loss of taste and/or smell Atypical Presentation  Fever has been present in ~44% of admissions yet ~89% developed fever during their hospitalization  GI symptoms: diarrhea and nausea prior to the onset of other respiratory symptoms  Altered mental status  Atypical Pneumonia  Bilateral findings: 85% of case  Predominately peripheral  Predominantly posterior  Definitive diagnosis:  Nucleic acid amplification testing (NAAT)  Better yield earlier in the course of the disease test Diagnostics  Other Labs  CBC  CMP/BMP  PT/INR  EKG  >90% on days 1-3,  Troponin  <80% at day 6,  COVID rapid test  <50% after day 14  +/- flu  Antigen Testing  Useful when NAAT not available  Used for serial screening and selftesting  High specificity but less sensitive than NAAT  Serology  Less likely to be reactive at the beginning of infection  Utilized 3-4 weeks after the onset of symptoms.  Viral cultures  Only reserved for research purposes  Imaging  Chest X-ray  Range from normal to consolidation/opacities/ bilateral /lower lung involvement.  Pneumothoracies.  Chest CT:  NOT recommended for screening, reserve for inpatient management  Ground glass opacities  Pleural thickening  Interlobular septal thickening  Air bronchograms  Mild    Managemen t disease Supportive care only Close monitoring Educate patient for signs and symptoms of concern  Outpatient management  Antiviral Paxlovid (Nirmatrelvir with Ritonavir)  Age 12yrs and older  PO route, Preferred therapy at this time  Moderate sxs for <= 5 days  Adverse effect: many drug-to-drug interactions  Monoclonal antibody Bebteloviman  Recommended second choice  High risk pts w/ serious disease progression  Sxs <7days. Close contact with someone who tested positive  Antiviral Remdesivir     Adults and children Given within 7 days of sxs onset IV route Some early studies have shown improved outcomes in pregnancy Inpatient management  Empiric treatment for influenza and bacterial pneumonia when indicated  Fever reducers: acetaminophen preferred  Avoidance of nebulized medications  Prevention of venous embolism with LMWH  Patients NOT requiring oxygen:  Remdesivir (Veklury) Managemen t  Patients requiring oxygen or severe disease:  Remdesivir  Dexamethasone  Patient requiring mechanical ventilation or ECMO:  Dexamethasone  Tocilizumab or baricitinib  Steroids  Only in severely ill and requiring O2 or ventilator  Dexamethasone PO or IV  Extracorporeal Membrane oxygenation (ECMO)  Patients placed in prone position  Intubation ECMO Proning Patients faced prone for 1618 hours then placed horizontally for 6-8hrs  Respiratory Failure  ARDS  Cardiovascular  Arrythmias, acute cardiac injury, shock, myocarditis, SIRS, hypoxic injury  Thromboembolic  PE, CVA Complications  Neurologic complications:  Encephalopathy, stroke, ataxia, seizures, movement disorders, sensory disorders  Inflammatory  Elevated inflammatory markers, fevers, elevated proinflammatory cytokines  Associated with severe dz and high mortality rate  Guillain-Barre Syndrome, Kawasaki Dz, toxic Shock Syndrome  Secondary Infection  Fungal infections  Bacteremia  Aspergillosis  Milder Infections:  Recovery ~2 weeks  Age dependent  Prolong symptoms lasting longer than 30 days: cough, fatigue, fever, chills Recovery time  Severe Disease:  3-6 weeks to recover from acute illness  Patients have been reported to have symptoms that continue well into 60 days past initial illness: fatigue, dyspnea, joint pain, chest pain  Neuropathy Post COVID syndrome  Difficulty with breathing or dyspnea  Diarrhea  HA  Fever  Fatigue  Dizziness, lightheadedness  Symptoms that worsen with mental or physical activity  Rash  “Brain fog”  Cough  Chest or stomach pain  Palpitations  Arthralgias, Myalgias  Insomnia  Mood changes  Change in smell or taste  Change in menstrual cycles Prevention  mRNA vaccination  Evusheld (Tixagevimab + cilgavamib):  Preexposure prophylaxis: recent known contact  In investigational status  For those who cannot be vaccinated or have had an inadequate response to vaccine  Combination of 2 monoclonal antibodies  1 dose of 2 IM injections Vaccine MOA The End