Colds and common viral illness Flashcards

Question

Other labs:

Answer 1

􀀀 In measles not complicated by bacterial infection, the erythrocyte sedimentation rate and C-reactive protein levels are normal. 􀀀 Serologic confirmation may also be made by demonstration of a 4-fold rise in IgG antibodies in acute and convalescent specimens taken 2–4 wk later. 􀀀 Viral isolation from blood, urine, or respiratory secretions can be accomplished by culture at the Centers for Disease Control and Prevention (CDC) or local or state laboratories. 􀀀 Molecular detection by polymerase chain reaction is possible but is a research tool. b. Management b.1. Goals of Management: 􀀀 Management of measles is supportive. Maintenance of hydration, oxygenation, and comfort are goals of therapy. b.2. Pharmacologic Management 􀀀 Antipyretics for comfort and fever control b.3. Non-pharmacologic management 􀀀 Oral fluids 􀀀 Eye care 􀀀 Nutrition b.4. Anticipatory care 􀀀 Developmental surveillance 􀀀 Dental health care 􀀀 Avoidance of injury 􀀀 Child protection vs maltreatment 􀀀 Immunization 􀀀 Proper nutrition Others*: 􀀀 Vitamin A supplementation Oxygen support (For patients with respiratory tract involvement, airway humidification and supplemental oxygen may be of benefit while respiratory failure due to pneumonia may require ventilatory support_

Answer 2

* Children 6 mo to 2 yr of age hospitalized with measles and its complications (e.g., croup, pneumonia, and diarrhea). * Children >6 mo of age with measles who are not already receiving vitamin A supplementation and who have any of the following risk factors: * Immunodeficiency * clinical evidence of vitamin A deficiency * impaired intestinal absorption * moderate to severe malnutrition * recent immigration from areas where high mortality rates attributed to measles have been observed Single dose of 200,000 IU orally for children ≥1 yr of age (100,000 IU for children 6 mo to 1 yr of age) * The dose should be repeated the next day and again 4 wk later for children with ophthalmologic evidence of vitamin A deficiency

Answer 3

􀀀 Otitis media 􀀀 Measles pneumonia – Giant cell pneumonia 􀀀 Dehydration 􀀀 Subacute Sclerosing Panencephalitis

Answer 4

5. How can this illness be prevented? 􀀀 Vaccination with measles vaccine Administration of measles vaccine to children, adolescents and adults with incomplete or no vaccination using the monovalent or trivalent vaccine (contains measles, mumps and rubella). A tetravalent vaccine, MMRV (contains measles, mumps, rubella and varicella) may be used for infants 12 months to 12 years of age 􀀀 Indications: o For those who have not received any dose of the measles vaccine, they should receive 2 doses 1 month apart o For those who have received 1 dose of measles vaccine at 12 months of age or older, administer the second dose o For those with unknown history of measles vaccination, give measles vaccine for 2 doses 1 month apart o Children 6 months to 11 months of age should receive measles vaccine and followed by 1 dose administered on or after the first birthday, preferably between 12-15 months of age, then another dose at least 1 month after and usually given at 4-6 years o In outbreak areas, where measles involves infants <12 months of age and have ongoing risk of exposure, measles vaccine can be given as early as 6 months o Individuals exposed to measles should receive measles vaccine (monovalent or trivalent vaccine) within 72 hours of exposure

Answer 5

Rubeola Etiology: - Paramyxovirus - Humans are the only host of measles virus - Prolonged immunosuppression x 2-3 yrs - Most infectious virus (r knot 12-18)

Answer 6

- The status of vaccine coverage is important in the epidemiology of measles - High measles vaccination coverage early in life are essential to maintain the endemic spread (>90% at 12- 15mos, and >95% 2 dose coverage in school age) - Outbreaks due to lower coverage rates of vaccination due to personal belief - Indicator of weakness of immunization program (geographic) - Risk for complicated disease: a. <5 yo, >20yo b. Malnourished c. Insufficient vit A d. Weak immune system (AIDS)

Answer 7

Transmission: - Respiratory tract/conjunctiva after contact with large droplets or small droplet aerosols - Virus viable in droplet for 1h, and 2h on surfaces - 90% of exposed individuals are susceptible to measles

Answer 8

4 Phases: 1. Incubation period – measles migrates to regional LN primary viremia to RES à secondary viremia to body surfaces 2. Prodromal illness – epithelial cell necrosis and giant cell formation in tissues. Cell death via viral replication, viral shedding begins. 3. Exanthematous phase – onset of rash. Ab production. Viral replication & sx subside. Immunosuppression of Th1. 4. Recovery phase

Answer 9

Period of communicability: 3 days before until 4-6 day after onset of rash Incubation period: 8-12 days (1-2w)

Answer 10

CM 1. Prodromal phase – fever, conjunctivitis, coryza, cough, photophobia - Koplik spots – pathognomonic. Grayish white dots with red border opposite lower molars. Enanthem. a. appear 1-4 days before rash b. also at lips, hard palate, and gingiva 2. exanthematous phase – after 1-4 days from onset of sx, usually at height of fever - rash: MP begins at forehead which spreads downward to torso, ext., palms, soles (craniocaudal dissemination/ centrifugal distribution) - x7-10d days and fade in the same pattern leaving fine/branny desquamation 3. recovery – cough lasts longest x 10d

Answer 11

Dx: Always clinical 1. CBC: dec WBC, dec lym

Answer 12

Complications: Highest M&M at 5yo (esp <1 yo) and >2 yo 1. PN – most common cause of death (giant cell PN) or bacterial superinfection (S.pneumonia, S.aureus, HiB) 2. AOM – most common complication 3. Croup, tracheitis, bronchiolitis 4. Febrile sz 5. Encephalitis 6. Subacute sclerosing panecephalitis (SSPE) - 1-10mos after infection (immunocompromised) - Sz, myoclonus, stupor, coma - Nearly always fatal - Secondary to persistent infection with an altered measles virus in intracellular CNS - After 7-13 yrs, attack CNS à inflammation à cell death à neurodegenerative process - Risk factors: a. 20% measles <2yo b. 75% measles <4yo - S/Sx: a. Stage I: behavioral changes, irritability, dec attention, temper outbursts b. Stage II: massive myoclonus c. Stage III: choreoathetosis, immobility, dystonia, lead pipe rigidity, dec. sensorium, coma Dx: a. S/Sx + CSF measles Ab b. EEG: suppression-burst episodes c. Biopsy – show evidence of astrogliosis, neuronal loss, degeneration of dendrites, demyelination, neurofibrillary tangles, and infiltration of inflammatory cells - Tx: supportive - Death in 1-3 yrs 7. Hemorrhagic/black measles – hemorrhagic skin eruptions, fatal 8. Bronchiolitis obliterans – final common PW to an obliterative outcome

Answer 13

Mgt 1. Supportive 2. Vitamin A – for all pxs 200,000 IU OD x 2 d >12mo 100,000 IU 6-11mo 50,000 IU <6mo Prevention - Viral shedding = 7 days after exposure to 4-6 d after onset of rash 1. Standard and airborne precautions 2. Isolation 3. MMR/measles vax @ 9mos, then at 12-15mos, then 4- 6yo - Protective of SSPE - AE: fever, rash (rare) – 6-12d after vax - PEP if within 72h after exposure 4. IVIG – 0.25ml/kg within 6d after exposure for <6mo, pregnant, immunocomp

Answer 14

CH 248: MUMPS - Rubulavirus Transmission: - Respiratory droplets Period of communicability: 1-2 days before to 5 days after parotid swelling Incubation period: 16-18 d (12-25d)(2-3w)

Answer 15

Patho - Virus targets the salivary glands, CNS, pancreas, testes > thyroid, ovaries, heart, kidneys, liver, joint synovia --> viral replication at epithelium of URT --> LN spread to tissues --> necrosis of infected cells and lymphocytic inflammatory infiltrate

Answer 16

CM: 1. 1-2 days prodrome of fever, headache, vomiting, myalgia, then parotitis 2. Parotid swelling and tenderness, peaks in 3d then gradually subsides over 7d, bilateral (70%) 3. Angle of jaw obscured as swelling ensues and earlobe lifted upward and outward 4. Edema over the sternum due to lymphatic obstruction

Answer 17

Dx: Usually clinical 1. CBC – leukopenia with relative lymphocytosis 2. Mumps IgM, IgG 3. Viral culture – gold standard, buccal/oral swab 4. Immunofluorescence – detect viral Ag 5. RT-PCR – samples URT secretions, urine, CSF during acute phase 6. Elev Serum amylase

Answer 18

Supportive – antipyretics, pain relief, adequate hydration

Answer 19

Complications 1. Meningitis w/ or w/o encephalitis – most commonly manifests 5d after parotitis. Sx resolve in 7d 2. Orchitis – 30-40% of postpubertal males. Begins within days after onset of parotitis, HG fever, chills, exquisite testicular pain and swelling, B (30%). Sterility is rare 3. Pancreatitis, myocarditis, PN, optic neuritis, conjunctivitis, nephritis, thrombocytopenia prevention: MMR vaccine

Answer 20

- German Measles/3-day measles - Togavirus - Usually pre-school and school-age children - Epidemiology relative to Rubella vax

Answer 21

- Virus replicates in the respiratory epithelium then to regional LN (10-17d) - Viral shedding = 10d after infection to 2 weeks after rash onset - in fetus: causes tissue necrosis due to vascular insufficiency, reduced cellular multiplication time, chromosomal breaks, and production of protein inhibitor causing mitotic arrests - Chronicity – most distinctive feature. Virus persists until postpartum

Answer 22

Transmission: - Droplet, respiratory, stool, urine, cervical - transplacental Period of communicability: 5 days before to 6 days after rash onset Incubation period: 14-21d (2-3wks)

Answer 23

Risk factor: 1. Pregnant women – most impt for congenital defects - 1st 8 weeks AOG – most severe and widespread defects a. <11 wks -90% risk b. 11-12 wks – 33% c. 13-14 wks – 11% d. 15-16 wks -24 % e. >16 wks – uncommon - Thus, early infection (1-12 wks) higher risk of congenital defects and higher risk to fetus - Pregnant woman develops mononucleosis-like illness

Answer 24

CM: 1. Prodrome – LG fever (dec in T on D3-4 when rashes appear), sore throat, red eyes+pain, headache, flu-like sx, LNE 2. Suboccipital, postauricular, anterior cervical LNE - Begins 24h before rash & remains for 1 wk 3. Rash – pink macules that spread centrifugally (from face, neck à torso and ext, discrete x3d. resolves without desquamation 4. Forchheimer spots – tiny, rose colored spots at soft palate. Appear at same time as rash 5. No photophobia

Answer 25

Dx: 1. CBC – dec WBC, dec neu, plt 2. Rubella IgM, IgG – 4x increase is diagnostic, taken before 3 mos old 3. C/S – can be done until 1 yr of illness (nasopharyngeal swab, conjunctival scrapings, urine, CSF_ 4. PCR (+) 5. CSF – encephalitis with inc protein and cell count

Answer 26

Complications 1. Thrombocytopenia 2. Arthritis – after 1 week, fingers 3. Encephalitis – most serious 4. Progressive Rubella Panencephalitis (PRP)– like SSPE 5. GBS, myocarditis, neuritis

Answer 27

Congenital Rubella Syndrome (CRS) CM: 1. Hearing loss/sensorineural deafness – single most common sx in infants, most common sx 2. IUGR 3. Salt and pepper retinopathy – most common eye sx 4. Cataract – most serious eye sx 5. microphthalmos 6. PDA – most freq heart defect 7. CV: PAS, valvular pulmonic stenosis 8. Interstitial pneumonitis 9. Blueberry muffin rash 10. Meningoencephalitis 11. Psychomotor retardation, MR, speech and language delay 12. Death Tx: 1. Supportive 2. IVIG, CS – for severe, non-remitting thrombocytopenia 3. Hearing screening – for early intervention of CRS Prevention 1. Isolation x7d after rash onset 2. Standard & droplet prec 3. CRS: contact precaution until 1yo (viral secretion in respiratory secretions) 4. Rubella IgG -for pregnant women; repeated at 2wks, 6 wks 5. MMR/MMRV vax - @12-15mo (#1), then @4-6yo (#2) - CI: severe immunocomp, pregnancy - AE: fever, rash

Answer 28

Enanthem subitum/6th disease - Human Herpesvirus (HHV)6B, 7

Answer 29

Epid: - Peak age @6-9mos following loss of maternal Ab, usually <3yo - Sporadic, (-)seasonal predilection, (-)contact exposure Transmission: - Saliva, respiratory droplets - Vertical transmission = transplacental infection and chromosomal integration Communicability: unknown Incubation period: 9-10d

Answer 30

CM 1. Fever – HG (>39.7C) x 3-5d, abrupt, usually acutely resolves after 72h (“crisis”) or gradually fades over the day “lysis” coincident with appearance of rash 2. Rash – blanching, MP, faint, pink, nonpruritic on trunk x 1-3d, evanescent spreading to face and ext. (centripetal) 3. Pharyngeal injection, palpebral conjunctiva, TM 4. Bulging of anterior fontanelle 5. Suboccipital LNE 6. Nagayama spots – ulcers at uvulopalatal junction 7. Fussiness, irritability 8. Colds, congestion 9. GI sx 10. Encephalopathy, convulsions Mean duration = 6d (3d fever + 3d rash)

Answer 31

Dx: Mainly clinical = 3d fever with blanching MP rash in nontoxic 6- 10mo child 1. CBC – dec WBC, lym, neu, plt 2. Elev serum transaminase 3. MRI – hyperintense T2 images at amygdala, hippocampus, uncus 4. Viral C/S – gold standard 5. PCR

Answer 32

Complication 1. Convulsion – most common, peak at 12-15mo 2. Encephalitis, cerebellitis 3. Hepatitis 4. Myocarditis 5. Developmental abN, autism Tx: supportive Prognosis: self-limited with complete recovery

Answer 33

- Fifth disease - Parvovirus B19, bocavirus - 5-15yo Transmission: - Respiratory route via large droplet, blood, blood products

Answer 34

Patho: - Viral tropism to erythroid cells à dec plt and neu - Biphasic illness a. After inoculation, at 7-11d = viremia & viral shedding. Fever, malaise. b. @17-18d = rash, arthralgia

Answer 35

Communicability = before onset of the rash until after the onset of rash Incubation period = 4-28d (ave 16-17d)

Answer 36

CM 1. Benign, self-limited 2. Prodrome – LG fever, headache, URTI 3. Rash = 3 stages: a. Slapped cheek appearance – erythematous, facial flushing b. Rash spread to trunk, ext, diffuse macular erythema c. Lacy, reticulated rash, macular, with central clearing, esp extensors. Sparing palms and soles. Wax and wane X 1-3w - Atypical skin eruption: papular-purpuric “gloves & socks” syndrome (PPGSS), then fever, pruritus, painful edema & erythema localized to distal extremities, followed by acral petechiae & oral lesions

Answer 37

Mainly clinical 1. CBC – WOF for low Hgb in aplastic crisis 2. Low reticulocyte count 3. B19 IgM – (+) for 6-8wks, recent/acute infection 4. PCR – detectable for 4 months

Answer 38

Supportive

Answer 39

Complication: 1. Arthralgia, arthritis 2. Transient aplastic crisis – fever (-)rash. Chronic hemolysis, rapid RBC turnover, severe anemia 3. In pregnant women = miscarriage, intrauterine death (<5%), hydrops fetalis, bone lesions a. Most sn period = 2nd trimester b. No tx Prevention: 1. Isolation not necessary, rash is postinfectious

Answer 40

Epid - Lifetime risk for zoster 20-30%, >45yo 75% - Lifelong latent infection -- > dorsal/sensory ganglia

Answer 41

communicability: 1-2d before rash until vesicles are crusted usually 3-7d after rash onset Incubation period: 10-21d (1-3w) Transmission - Airborne spread, direct contact with secretions (oral and skin)

Answer 42

Patho - Virus inoculated in the URT and tonsillar lymphoid tissue --> viremia spreads to the RES--> infection in lungs, liver, brain, etc (chickenpox) --> virus transported retrogradely through sensory axons to the dorsal root ganglia of SC --> latent infection (herpes zoster)

Answer 43

1. Chickenpox - Sx start 14-16d after exposure - Fever (37.8-41.1C) - Anorexia, headache - Mild abdominal pain - Rash – intensely pruritic erythematous macules to papules to vesicles at scalp, face, trunk. Simultaneous presence of lesions at various stages of evolution. Central/centripetal distribution (most at trunk, prox.ext) - Ulcerative mucosal lesions (oropharynx, vagina) - Complications: a. Secondary bacterial infection – skin, PN, sepsis, arthritis b. Encephalitis & cerebellar ataxia – highest morbidity <5yo or >20yo § Begins 2-6d after rash c. Meningitis d. Reye syndrome e. GN 2. Herpes zoster - Vesicular lesions clustered within 1-2 adjacent dermatomes with pain, hyperesthesia, pruritus, LG fever - Usually 1-2 weeks, milder in children - Complic: Postherpetic neuralgia 3. Neonatal varicella - High mortality rate - Mom with VZV 5 days before delivery to 2 days afterward are at risk for severe varicella a. Transmission: transplacental from maternal viremia. b. Mom has not yet developed significant Ab response, infant receives large viral load w/o maternal Ab - Mom with VZV >5 days prior to delivery a. Attenuated infection due to maternal Ab b. Esp after 30 weeks AOG a. Rash – 2d to 2nd week of life b. PN, hepatitis, encephalitis 4. Congenital/Fetal varicella syndrome (CVS) - Mom with VZV during 1st half of pregnancy (8th-20th week) - <13wks AOG (0.4%) 13-20wks AOG (2%) - Virus spreads to all fetal organs hematogenously a. Rash – cicatricial skin scarring, dermatomal distribution b. Limb hypoplasia c. CNS: microcephaly, cortical & SC atrophy, sz, MR, encephalitis, cerebral calcifications d. Eye: chorioretinitis, microphthalmia, cataract, optic atrophy, nystagmus, Horner syndrome (ptosis, miosis, enophthalmos) e. Renal: hydroureter, hydronephrosis f. ANS: neurogenic bladder, swallowing dysfunction, aspiration PN g. LBW, PT, IUGR h. 30% die within first 4 mos i. High risk to develop zoster in first 2 yrs j. Pneumonitis - Dx: PCR

Answer 44

1. CBC – dec WBC during 1st 72h of rash, then lymphocytosis 2. Elev LFT 3. PCR – most sn (fetal blood and amniotic fluid) 4. VZV IgG – after 2-3 weeks for chickenpox a. for CVS, @>7mos or VZV zoster @1yo 5. cranial UTZ – for CVS, cortical atrophy, dilated ventricles

Answer 45

Mgt: 1. Acyclovir – 20mkdose q6h x 5d for: a. Nonpregnant >12yo b. On CS tx, ASA c. Most effective if started within 24h of rash onset until 72h d. For herpes zoster – 10mkdose q8 if with lesions e. For neonatal varicella f. Not indicated for CVS, but may be used to stop progression of eye ds or tx shingles (first 2 yrs of life) g. For mother if diagnosed during pregnancy 2. Famciclovir, valacyclovir 3. VZIG or IVIG – severe (PN, hepa, dec plt). - Given w/in 72-96h of exposure of mother 4. Supportive 5. VarizIg + Acyclovir – for pregnant, immunocomp, infants after exposure a. NB of mom with varicella 5 days before to 2 days after delivery b. PT infant <28wks AOG

Answer 46

Prognosis: Death due to PN, CNS, secondary infection, hemorrhage in infants and adults

Answer 47

VZV vax @12-15mos (#1), then 4-6yo (#2) - Min interval between doses: - <12 yo: 3mos - >12 yo: 4 wks - CI: pregnant, immunodef. - AE: rash (1-5%) 6-10 lesions at 8-21d after vax, PN, hepatitis, meningitis, zoster, sz (higher for MMRV at 12-23mos) - PEP - 3-5d after exposure Rash 0-42d after vax due to exposure and infection before vax, or secondary to vax Breakthrough varicella - >42d after vax due to wild type VZV. - VZV protects >97% from moderate to severe VZV after vax - Rash atypical, MP, <50 rashes, shorter duration, afebrile, fewer complications, less contagious Prevention Isolation until all lesions crusted (-)new lesions/vesicles

Answer 48

Virus is hepatotropic --> direct cytopathic and immune-mediated injury --> acute mixed inflammatory infiltrate à liver parenchyma necrosis, intact lobular architecture --> chronic hepatitis -->progressive scarring

Answer 49

1. Jaundice 2. AGE-like sx 3. Acute fever, anorexia, nausea, malaise, vomiting 4. LNE, splenomegaly 5. Rash – in HepB: urticarial, purpuric, macular, MP 6. Others: PAN, GN, aplastic anemia – for HepB

Answer 50

Dx 1. Elev AST, ALT – the magnitude of elevation does not correlate with the extent of hepatocellular necrosis and has little prognostic value 59 - Rapidly falling values indicate poor outcome, massive hepatic injury 2. Elev TB, DB, IB – cholestasis 3. Elev ALP, GGT, urobilinogen 4. Elev PT, INR, low serum albumin, metabolic disturbance (hypogly, lactic acidosis, hyperammonemia – reflects altered synthetic function, most impt marker of liver injury/ failure. Indication for transplant - Monitoring of synthetic function should be the main focus of clinical follow-up to define the severity of the ds. 5. Liver biopsy – only for chronic disease, to assess degree of damage and rule out other causes. Ground glass hepatocytes, finely granular, eosinophilic cytoplasm 6. Elastography – ID presence of elastosis

Answer 51

HEPATITIS A - Most prevalent hepatotropic virus - Responsible for most forms of acute and benign hepatitis - Most prevalent in developing countries - Highly contagious – most 2 weeks before and approximately 7 days after the onset of jaundice. Isolation. - Food-borne and waterborne outbreaks, contaminated shellfish, berries, vegetables

Answer 52

Transmission: - Infected blood or body fluids: serum, semen, vaginal secretions, CSF, synovial, pleural, pericardial, peritoneal, amniotic fluid (most infectious) - Percutaneous and permucosal exposure to fluids - Sharing unsterilized needles, syringes, or glucose monitoring equipment - Sharing inanimate objects such as razors, toothbrush - Sexual contact with infected person - Risk of transmission is greatest if mother is also HBeAg- (+) (90% of infants become chronically infected if untreated) - Perinatal exposure to infected mother in utero, during labor and delivery: a. Infants born to HBsAg(+), HBeAg (+) mother: 70-90% risk of HBV b. Infants born to HBsAg(+), HBeAg(-) mother: 5-20% risk of HBV Dx: 1. HBsAg – first marker to appear & its rise coincides with sx onset - Acute or chronic infection - During self-limited HBV, disappears a few weeks to several months after infection 2. Anti-HBs – indication of resolved HBV infection. Protective Ab to HBV - Determines immunity after vaccination (present long after HB vax) 3. HBeAg – identification of HBV infected at risk of transmitting HBV (highly infectious). qualitative - Serves as marker of active viral replication 4. Anti-HBe – transition from a state of high to low infectivity 5. Anti-HBc (total) – identification of acute, resolved, or chronic HBV infection - Passively transferred maternal Anti-HBc detectable for 24mos among infants born to HBsAg+ women 6. IgM anti-HBc – identification of acute or recent HBV infection - The only marker highly specific for establishing the diagnosis of acute HBV infection during the window phase of infection - Not reliable for detecting perinatal HBV infection 7. IgG anti-HBc – past or chronic infection 8. HBV DNA – indicates active viral replication, more accurate than HBeAg especially in cases of escape mutants. Used mainly for monitoring response to therapy. Quantitative 9. cccDNA – covalently closed chain DNA. New biomarker for infection.

Answer 53

HBsAg, HBeAg, HBV DNA, ALT, liver biopsy/ elastography – assessment of HBV infection Anti-HBs & total Anti-HBc = indicate resolved HBV infection HBsAg & total Anti-HBc = chronic HBV infection HBeAg & HBV DNA = useful in the selection of candidates for antiviral therapy for monitoring response to therapy “symptomatic, enfectious, chronic/case”

Answer 54

Never infected: (-)HBsAg, (-)Anti-HBs, (-)Anti-HBc, (-)HbEAg Incubation period: (+) HBsAg, (+)HBeAg Acute Infection: (+)HBsAg, (+)IgM Anti-HBc, (+)HBeAg Window period: (+)IgM Anti-HBc Complete recovery: (+)Anti-HBs, (+)IgG Anti-HBc Chronic carrier: (+)HBsAg, (+)IgG Anti-HBc Chronic active: (+)HBsAg, (+)IgG Anti-HBc, (+) HBeAg Vaccinated: (+) Anti-HBs

Answer 55

1. Acute infection – no specific tx available 2. Chronic infection – treatment to prevent cirrhosis, hepatic failure, & HCC - Requirements before considering tx: a. Persistently elevated ALT levels for at least 6 mos; at least 12 mos in HBeAg (-) b. ALT at least 1.5-2x N and ALT levels >60 IU/L c. HBV DNA >20,000 IU/ml d. Moderate to severe inflammation on liver biopsy - Special circumstances to start tx immediately: a. Inc risk of progression of disease: cirrhosis, HBV related GN, co-infection with HDV, HCV, or HIV b. FHx of HCC c. Recipients of grafts from anti-HBc (+) donors d. HBsAg (+) children who will receive cytotoxic or immunosuppressive tx 3. Tx of pax in the immune-active form of the disease as shown by increased levels of LFT, those with fibrosis on liver biopsy: a. Interferon-a2b (IFNa): for >1yo. for +HBeAg carriers with chronic active hepatitis. Response rate is 30-40%. IFN activates intracellular enzymes causing degradation of HBV mRNA First line tx for chronic HBV in children >1yo Dose: 5-10 M IU/m2 3x/week SQ for minimum of 6mos Definite duration of tx (6-12 mos) given 3x/wk Adv: no viral resistance, licensed for children >1yo, definite duration of tx Disadv: SC administration; AE: local and systemic (fever, myalgia, h/a); not used in decompensated liver disease, liver transplant and in those with autoimmune disorders b. Lamivudine – a nucleoside analogue (NA) with low barrier to resistance. Well tolerated. Most px will respond favorably. However, tendency to relapse on cessation of tx & rapid emergence of drug resistance (30%). Recommended for >3yo c. Adefovir – NA with low barrier to resistance. Recommended for >12yo d. Entecavir – NA with high barrier to resistance. For >2yo Slows down the stop signal causing elongation of DNA chain 2-18 yo, HBV DNA >20,000 IU/ml, ALT >1.5x Dose: 0.015 mg/kg (max 0.5 mg/d) x 96 weeks Adv: oral administration, high response rate with low resistance (2.2%), licensed for >2yo Disadv: long duration of tx; AE: renal dysfunction, hepatitis flare e. Tenofovir – NA with high barrier to resistance. For >12yo 4. Successful response to tx will result in disappearance of HBsAg, HBV-DNA, and seroconversion to HBeAg.

Answer 56

Hepatitis C

Answer 57

1. HCV Ab – generally used to dx hepatitis C infection. Not useful in acute phase as it takes at least 4 wks after infection before Ab appears 2. HCV RNA – PCR and branched DNA. Dx HCV infection in acute phase. Its main use is in monitoring response to antiviral tx. 3. HCV Ag – EIA for HCV. Used like HCV RNA, easier to carry out.

Answer 58

Mgt 1. Interferon – chronic HepC. Response rate 50% but 50% of responders will relapse upon withdrawal of tx 2. Ribavirin – combined with interferon is more effective

Answer 59

Patho: - Destroys villus tips à decreased absorption of salt, water and imbalance of absorption to secretion - Complex CHO and lactose malabsorption

Answer 60

CM: 1. Diarrhea – freq, watery stools, severely dehydrating x 5-7d 2. Mild to moderate fever, vomiting x 1-2d 3. Dehydration with acidosis

Answer 61

Dx: Mostly clinical. 1. Isotonic dehydration with acidosis - is the most common finding 2. Fecalysis – no WBC, RBC 3. ELISA

Answer 62

Tx: 1. supportive – tx dehydration and maintain nutrition 2. ORS 3. After rehydration, resumption of normal diet – allows more rapid recovery 4. BF, lactose-free diet Preventive: 1. Rotavirus vaccine – given at 2,4,6 mos before 32 weeks old

Answer 63

Dogs - >90% of human cases worldwide Rabies carriers – dogs, cats, bats Rare – mice, rabbits Transmission: 35-50% secondary to bite from infected animal (-)PEP High risk: bite at highly innervated part (face, hands) does not enter intact skin may enter mucus membranes Inoculation at skin/mucosa --> long incubation period at muscle/skin --> peripheral motor nerve à fast travel q12h --> rapid dissemination through brain, SC Infection concentrates at brainstem – autonomic dysfunction (cognition spared)

Answer 64

Negri bodies

Answer 65

2 Clinical Forms 1. Encephalitic/”Furious rabies” - Fever, sore throat, headache, malaise, nausea, vomiting, paresthesia and pruritus at bite site then extend along limbs --> - encephalitis – agitation, depressed mentation, sz a. characteristically periods of lucidity alternating with profound encephalopathy b. cardinal signs: hydrophobia, aerophobia - phobic spasms – agitation and fear after offered drink/fanning of air in face --> pharyngeal. Neck, diaphragm spasm --> choking, aspiration - death within 2 d 2. Paralytic/”dumb” rabies - Fever, ascending motor weakness of B limbs & CN - Encephalopathy

Answer 66

DDx: 1. Tetanus 2. NMDA encephalitis, other infectious enceph 3. Psychiatric illness 4. Drug abuse

Answer 67

Dx: 1. Rabies RT PCR – most sn. Sample saliva, serum, CSF 2. Skin biopsy of hair follicle at base of neck – Negri bodies 3. Viral culture 4. ABG – respiratory alkalosis from hyperventilation during acute phase, then respiratory acidosis as respiratory depression progresses 5. CBC – WBC N or elev, atypical monocytes 6. CXR – r/o aspiration PN, nosocomial PN, ARDS, CHF 7. Brain MRI or CT scan – usually N. nonspecific low level T2 enhancement along the nerve plexus and nerve root ganglia 8. EEG – during the 1st week, amplitude drop mimicking brain death due to the generalized vasospasm of cerebral arteries 9. ECG – SVT then eventually bradycardia and cardiac arrest

Answer 68

Mgt Rabies is generally fatal! Supportive RIG/vax no benefit once sx’c

Answer 69

Prevention 1. Routine rabies vax for domestic pets (dogs, cats) - If a vaccinated pet bites you (annually updated, confirmed), no PEP need to be given - If undocumented/unconfirmed/unupdated à give PEP 2. Post-exposure prophylaxis (PEP) CCDV – modern concentration & purified cell culture derived vax Rabies PEP should be given ASAP Pregnancy & infancy are not CIs to PEP Patients presenting for rabies (even months after a bite) should be treated as if contact is recent PEP should be given even if animal cannot be observed. - Vax & RIG may be d/c after 10 days of animal observation if vaccinated pet is asx’c/lab test (-)

Answer 70

Category of exposure Category Description Mgt Cat I Lick intact skin No PEP Cat II Minor scratch/abrasion w/o bleeding PEP Cat III 1 or more transdermal bite/scratch on broken skin; lick on mucosa PEP + RIG ASAP at distant site. RIG may be given up to 7d after 1st vax dose

Answer 71

Regimens: Dose: 20 IU/kg HRIG or 40 IU/kg ERIG 1. 5 dose IM (1-1-1-1-1) - 1 dose of vax on days 0,3,7,14,28 at deltoid or anterolateral thigh 2. 2-1-1 IM (2-0-1-0-1) - 2 doses at day 0 at R/L deltoid then - 1 dose at day 7 and 21 3. 2 site ID method (2-2-2-0-2) - Uses less vax amount, cheaper, or if vax is on short supply - PVRV (Verorab) & PCECV (Rabipur) 0.1ml ID - 1 dose 0.1ml ID at 2 different sites (R & L deltoid or suprascapular area) at D0,3,7 & 28 4. Wound tx: - Done ASAP - Immediate washing & flushing x 15 min with water and soap - Disinfection with ethanol, iodine 5. ABX + Tetanus prophylaxis - Abx = co-amoxiclav (DOC) 20-40 mkd q8/12 po 6. Rabies Ig (RIG) - No need for skin testing for ERIG 7. Pre-exposure prophylaxis (PrEP) - Recommended for anyone with continual, frequent exposure or inc exposure a. Vets, animal handlers b. Rabies affected area residents c. Travelers to rabies affected areas a. 3 dose IM - 1 dose IM @ D0, 7, 21 or 28 at anterolateral thigh (<2yo) or deltoid (>2yo) b. 3 dose ID - 0.1ml ID at D0,7,21 or 28 - Then serum level q2yrs - Booster dose if titer <0.5 IU/ml

Answer 72

Transmission - Respiratory and fecal-oral routes - Can survive on inanimate objects Patho - Viremia causes damage to epithelial mucosa, sloughing of cell debris, and inflammation

Answer 73

CM 1. Conjunctivitis – self-limiting. Severe form (epidemic keratoconjunctivitis). a. Pharyngoconjunctival fever – distinct syndrome with HG fever, pharyngitis, nonpurulent conjunctivitis, preauricular and cervical LNE 2. URTI, LRTI – bronchiolitis, PN 3. Pharyngitis – coryza, sore throat, fever 4. AGE – self-limiting 5. Hemorrhagic cystitis – sudden onset hematuria, dysuria, frequency, urgency. Sterile pyuria (-) RBC. Resolves spontaneously after 1-2 wks 6. Myocarditis, hepatitis, meningoencephalitis

Answer 74

Dx: 1. Cx – required 2-7d 2. CBC – WBC N 3. ELISA - stool 4. Serum PCR

Answer 75

Mgt 1. Supportive 2. Cidofovir – for epidemic keratoconjunctivitis Prevention 1. Hand washing, disinfection

Answer 76

CH 265: NORWALK AGENT - Calicivirus - Important pathogen of human viral gastroenteritis - Most common cause of AGE in older children and adults Patho - Destroy villus (like rotavirus) Incubation period: <12h

Answer 77

CM: 1. Diarrhea – large, explosive outbreaks usually in schools, cruise, hospitals, often from a single food, shellfish/water 2. Vomiting, nausea – prominent 3. Duration 1-3d 4. Appears like food poisoning

Answer 78

Dx: Clinical 1. CBC – WBC N, slight PMN leucocytosis, lymphopenia 2. ELISA 3. E’, BUN, Crea – if with dehydration (isotonic) 4. Fecalysis – (-) WBC, leu, (-) occult blood; to r/o other enteroinvasive infectious diarrhea 5. SCx – r/o Yersinia, Shigella, Salmonella, Campylobacter 6. CBC – elev WBC (stress-induced) Tx Supportive, ORS

Answer 79

Etiopatho - Influenza virus types A, B, C Influenza A – causes epidemics - Has animal host - Subtypes (based on surface Ag Hemagglutinin and Neuraminidase): H & N Influenza B – causes epidemics. Has no animal host Influenza C – causes sporadic mild flu-like illness

Answer 80

- Antigenic drift: minor antigenic variations may occur within types A & B that result in new strains leading to seasonal epidemics - Antigenic shift: major antigenic changes in influenza A viruses resulting in new HA or NA which can result in pandemics

Answer 81

Respiratory droplets - Contact with respiratory droplet-contaminated surfaces followed by autoinoculation - Viral shedding in nasal secretions peak on 1st 3 days of illness and cease within 7d

Answer 82

Patho - Infect the respiratory tract epithelium, primarily ciliated columnar epithelial cells, by using the HA to attach to sialic acid residues à lytic infection of the respiratory epithelium, dec mucus production, desquamation of epithelial layer à sec. bacterial invasion Incubation period: 1-4d

Answer 83

CM 1. Abrupt onset of HG fever, coryza, conjunctivitis, pharyngitis, dry cough, myalgia, malaise and headache 2. Majority recover fully after 3-7d

Answer 84

Complications 1. Otitis media 2. PN 3. febrile sz to encephalopathy/encephalitis 4. Reye syndrome 5. myocarditis 6. invasive secondary bacterial infections

Answer 85

Dx 1. CBC – leukopenia (lymphopenia) 2. hemagglutination inhibition test – during acute & convalescent stages 3. viral C/S 4. RT-PCR

Answer 86

Mgt 1. Supportive tx. 2. Do not give ASA 3. Oseltamivir x 7d – >1yo; within 48h may decrease the severity & duration <12yo: 12-60 mg po q12; >12yo: 75 mg po q12 4. Amantadine, Rimantadine – prophylaxis and tx of type A outbreaks

Answer 87

CH 250: NON-POLIO ENTEROVIRUS - Nonspecific viral illness - GIT: primary site of invasion and replication and source of transmission - Enterovirus (poliovirus, coxsackie A & B, echovirus) - Year-round in tropical and subtropical areas - Humans are the only known reservoir - Risk factors: young age, male, children exposure, poor hygiene, overcrowding, low SE status - Protective factor: BF

Answer 88

Transmission: - Fecal-oral route, respiratory route, fomites Patho - Replicates in the pharynx and intestines à LN tissue (tonsils, Peyer patches, regional LN) à CNS, heart, liver, lungs, pancreas, kidneys, muscle and skin à cell damage by necrosis and inflammatory response Incubation period: 3-6d

Answer 89

CM 1. HFMD 2. Herpangina – sudden fever (41C)x1-4d, sore throat, vesicles, dysphagia, lesions in posterior pharynx. Characteristic lesions present on the anterior tonsillar pillars, soft palate, uvula, tonsils, posterior pharyngeal wall, posterior buccal surfaces, discrete 1-2mm vesicles and ulcers that enlarge over 2-3d to 3-4mm and surrounded by erythematous rings upto 10mm. sx resolve in 3-7d. a. Coxsackie A 3. Acute Hemorrhagic conjunctivitis – airborne transmission, eye-hand-fomite-eye transmission. IP 1- 3d. b. Enterovirus, coxsackie A c. Sudden severe eye pain, with photophobia, OM, lacrimation, lid edema, LNE, subconjunctival hemorrhages, punctate keratitis, eye discharge. Recover in 1-2wks 4. Myocarditis, pericarditis 5. Meningitis – brainstem lesions. Most common cause of viral meningitis in mumps immunized populations 6. Nonspecific febrile illness – most common sx, esp infant and young children. Fever abrupt (38.5-40C), malaise, irritability, lethargy, anorexia, diarrhea, nausea, vomiting, abd discomfort, rash (macular, MP, vesicle, petechiae), sore throat, RTI, cervical LNE. Last 4-7d. 7. Pleurodynia (Bornholm disease) – coxsackie B, echovirus d. Epidemic or sporadic paroxysmal thoracic pain, due to myositis of chest and abdominal wall, pleural inflammation 8. Neonatal infection – ranges from asx’c to mild to severe disease.

Answer 90

Dx: Clinical 1. CBC – WBC N or mildly elevated, with neutrophilia, or leukocytosis 2. E’ – to r/o electrolyte imbalance 3. Viral C/S 4. RT-PCR – CSF, serum, urine, conjunctiva, nasopharyngeal, throat, tracheal, rectal, stool

Answer 91

Tx: 1. Supportive 2. IVIG – for severe ds Prevention 1. Hand hygiene, disinfection 2. Chlorination of water, pools 3. In pregnant women, do not terminate pregnancy, allow fetus to passively acquire protective Ab

Answer 92

- Coxsackie virus A16, enterovirus71

Answer 93

Epid: - Enterovirus circulate year-round in tropical areas - >25% in <1yo - BF protective due to maternal Ab - Commonly affects <10yo Risk factors: - Young age, female - Exposure to children, poor hygiene, overcrowding, low socioeconomic status Transmission: - Fecal-oral route, Respiratory route, fomites - Vertical transmission, BF Incubation period: 3-6d Communicability: via RT: <1-3wks Via feces: 7-11wks

Answer 94

Patho - Initial replication at pharynx, intestines --> LN, tonsils, Peyer’s patches --> minor viremia at RES (liver, spleen, BM, LN) --> major viremia to target organs (CNS, breast, skin)

Answer 95

CM: 2. LG fever x1-2d then 3. Inflamed oropharynx 4. Enanthem – vesicles and ulcerations at tongue, buccal mucosa, pharynx, palate, gingiva, lips; then 5. Exanthem – tender MP, vesicular, pustular @ hands> feet, butt, groin, palms and soles. Vesicles resolve after 1 week

Answer 96

Complications (more severe ds w/ entero71) 1. Neurologic ds, Encephalitis, encephalomyelitis 2. Acute flaccid paralysis 3. Myopericarditis 4. Shock 5. Pulmonary edema 6. hemorrhage

Answer 97

Dx: Clinical 1. PCR 2. Viral C/S – gold standard Mgt Supportive Prevention Good hygiene, handwashing, avoid sharing of utensils & drinks, disinfection of contaminated surfaces, chlorination of pools

Answer 98

- Polio virus 1, 2, 3 - Wild-type poliovirus (Type 1) - Circulating vaccine-derived poliovirus (cVDPV) – Type 2. Cause outbreaks - Community protection requires vaccination of >95% of the population

Answer 99

Transmission: - Fecal-oral Communicability: shortly before and after onset of sx. Virus persists in throat until a week after onset and excreted in the feces for 3-4wks Incubation period: 7-21d

Answer 100

Patho - Virus primarily replicates in the small intestines. Virus seeds multiple sites (RES, brown fat, skeletal muscle, CNS) --> affect motor and vegetative neurons --> inflammatory reaction with both PMN leukocytes and lymphocytes --> extensive neuronal destruction, petechial hemorrhages, edema --> >50% neuron destroyed results to limb weakness, hyperesthesia, myalgia - Primarily infects motor neuron cells in the SC (anterior horn cells) and medulla oblongata (CN nuclei) - cVDPV do not replicate in the CNS: safety of vaccine

Answer 101

CM Abortive PM – fever, malaise, anorexia, headache for 2-3d. complete recovery Nonparalytic PM – intense headache, nausea, vomiting, sore stiff neck, trunk, limbs a. Minor/1st phase: sx free interlude b. Major/2nd phase: CNS: nuchal & spinal rigidity, elev/dec DTRs, (-) sensory defects Paralytic PM 1. Spinal paralytic PM a. 1st phase – abortive PM. Px feels better after 2-3d b. 2nd phase – severe headache, fever, severe ms pain (lower back), sensory & motor sx (paresthesia, hyperesthesia, fasciculations, spasm, dec DTR § PE: spotty paralysis – 1/multiple/groups of ms, any pattern paralysis c. Asymmetric flaccid paralysis/paresis – after 1-2d. usually 1 leg à 1 arm. Proximal extremities > distal ext § PE: nuchal rigidity, ms tenderness, dec DTR d. Paralytic phase – bowel and bladder dysfunction, constipation, urinary retention 2. Bulbar PM - Dysfunction of CN and medulla a. Nasal flaring b. Dysphagia c. Accumulation of saliva à irregular respiration d. Ineffective cough e. Nasal regurgitation f. Desaturation of palate, uvula, tongue g. ANS: irregular RR, hypertension, arrhythmia, flushing, T changes h. Vocal cord paralysis – hoarseness, aphasia, asphyxia i. Rope sign – acute angle between chin & larynx j. Ultimately leading to shock, respiratory failure, coma à fatal! 3. Polioencephalitis a. Seizure, coma, spastic paralysis, elev DTR, irritability, disorientation, drowsiness, CN paralysis, respiratory insufficiency

Answer 102

Dx: 1. C/S – Isolation of virus: “BTS” a. Blood – end of 1st week b. Throat – end of 2nd week c. Stool – end of 3rd week. Collected 2x within 24-48h apart, highest in 1st week after paralysis. d. CSF 2. CSF analysis – N or pleocytosis (20-300 cells/uL) with early predominance of PMNs followed by a shift to mononuclear cells; N glc, inc proteins 3. CBC – leukocytosis 4. MRI – may show localization of inflammation to the SC anterior horns

Answer 103

Dx: 1. C/S – Isolation of virus: “BTS” a. Blood – end of 1st week b. Throat – end of 2nd week c. Stool – end of 3rd week. Collected 2x within 24-48h apart, highest in 1st week after paralysis. d. CSF 2. CSF analysis – N or pleocytosis (20-300 cells/uL) with early predominance of PMNs followed by a shift to mononuclear cells; N glc, inc proteins 3. CBC – leukocytosis 4. MRI – may show localization of inflammation to the SC anterior horns

Answer 104

Mgt 1. Bed rest and isolation 2. Supportive – IV, nutrition, bowel & bladder dysfunction support, tracheostomy 3. PT, OT, ST – to prevent contracture and joint ankylosis. ST for mgt of swallowing dysfunction Prognosis - Maximum paralysis usually after 2-3d after onset of paralysis. - Recovery phase x 6mo permanent Prevention 1. Oral poliovirus vaccine (OPV) a. Unimmunized person at imminent (w/in 4 weeks) risk of exposure to polio b. Contributes to herd immunity c. Induces intestinal mucosal immunity d. Vax of choice to interrupt transmission and rapidly stop outbreaks e. Bivalent OPV (bOPV) @ NCR – VDPV1 f. Monovalent OPV @ Mindanao – VDPV2 2. Inactivated poliovirus vaccine (IPV) a. HIV(+) b. Household contact of immunodeficient px c. Unimmunized person at future risk of exposure

Answer 105

Supplemental immunization activity (SIA) - Children until 59mo (<5yo) will receive 1 additional OPV dose regardless of previous doses a. To optimize immunity of susceptible pxs - Preferred are standalone IPV/OPV formulations (only available from govt) - Recommendations: 1. Primary series – 3 doses OPV/IPV at birth (0 dose) optional, 6 weeks, 10 wks, 14 weeks - A dose of IPV given with OPV @ 3rd dose 2. 2 booster doses @ 12-15mos (#1), and 4-6yo (#2) 3. <4yo missing booster doses: give 1st booster anytime then 2nd after 4 wks 4. >4yo: a. Unvaccinated: 3x OPV/IPV at 0,1,6 mos b. Incomplete vax: minimum interval b/n § dose 1&2 = 4 weeks § dose 2&3 = 6 mos § if missed, give missed dose There is no harm in receiving additional OPV doses. OPV is a supplemental dose given anytime (outside of routine vax sched) No minimum interval b/n IPV and OPV.

Answer 106

CH 260: RESPIRATORY SYNCITIAL VIRUS (RSV) - major cause of bronchiolitis and viral PN in children <1yo - most impt respiratory tract pathogen of early childhood - protective: BF - almost all children already had RSV infection by 2yo - highest incidence at 6wk-7mo old and dec freq thereafter incubation period: 3-5d

Answer 107

transmission: - droplets, airborne or fomites contact precautions sufficient to prevent spread Patho - RV-induced airway narrowing due to necrosis of bronchiolar epithelium, hypersecretion of mucus, round-cell infiltration and edema of surrounding mucosa à mucus plugs, obstructing bronchioles à hyperinflation or collapse of distal lung tissue

Answer 108

CM 1. rhinorrhea – 1st sign of infection 2. cough – after 1-3d 3. coryza, pharyngitis, fever, sneezing 4. otitis media 5. bronchiolitis – due to obstruction and collapse of small airways during expiration. Audible wheezing 6. PN – signs of respiratory distress 7. Diffuse fine inspiratory crackles and expiratory wheeze

Answer 109

Dx 1. CBC – WBC N or elev, N neu or mononuclear predominance 2. CXR – hyperexpansion of the chest, peribronchial thickening. The most important diagnostic concern is to ID bacterial or chlamydial involvement 3. RSV C/S – definitive dx 4. RT-PCR – using nasal mucus or nasopharyngeal specimen

Answer 110

Mgt 1. Humidified oxygen and suctioning – if hypoxic 2. IVF – moderately dehydrated Prognosis - Very low mortality rate Prevention 1. Contact precaution and isolation 2. Palivizumab 15mg/kg IM once a month for passive immunoprophylaxis for immunocompromised pxs, PT, CHD, CPD

Answer 111

- Persistently infected for 1 yr with intermittent secretion of CMV - Most common cause of congenital illness - Penetrates placental and BBB - Leading cause of deafness Transmission: 1. Community exposure – direct contact and secretions (saliva, urine) 2. Nosocomial – blood transfusion 3. Intrauterine (30%) - Perinatal: via genital secretions during SVD 4. Breastfeeding – most common route of CMV transmission in childhood (1st 6mo)

Answer 112

Patho - Lytic virus that causes cytopathic effects. - Pathologic hallmark are enlarged cells (cytomegaly) with viral inclusion bodies (“owl’s eye”)

Answer 113

CM: 1. Pregnant women - Teratogenic potential in the fetus during the 1st trimester - Mononucleosis-like syndrome 2. Congenital CMV infection a. Asx’c (90%) b. PT (<37 wks AOG) c. Jaundice d. Petechiae, purpura e. Hepatosplenomegaly f. Hepatitis g. PN, pneumonitis h. Triad: Microcephaly + cataract + periventricular calcifications i. Blueberry muffin rash j. SGA, IUGR k. Chorioretinitis l. Hearing loss – most common long-term sequelae (11%) m. Mortality rate = 20-30% (sepsis-like illness) n. Late complic: intellectual or developmental impairment, IUGR, microcephaly 3. Perinatal CMV a. Mild, asx’c, no tx required § Except for PT infant: severe

Answer 114

Dx: 1. Elev ALT 2. CBC - Dec plt (<100K), dec RBC 3. Direct hyperbilirubinemia 4. Cranial UTZ/CT scan – periventricular calcification 5. CMV PCR – urine at 1st 2-3 weeks of life (also saliva, blood) 6. Prenatal UTZ – cerebral abN (cerebral ventriculomegaly, occipital horn calcifications, PVL, microcephaly), non-cerebral multi-organ abN (echogenic bowel, ascites, hepatomegaly, cardiomegaly 7. Urine/saliva C/S – gold standard. Obtained before 3 wks of age 8. CMV IgM 9. CSF analysis, C/S – elev protein level, mononuclear leukocytosis

Answer 115

Mgt 1. None for immunocompetent 2. For congenital CMV - Ganciclovir 10 mkd q12h IV x 7-14d (induction) then 5mkdose OD for 6 wks IV, or 6mos po – for immunocompromised, sx’c infants - Hearing screening - Refer to Ophtha

Answer 116

Etiology 1. HSV type 1 - Affects face and skin above waist - Transmitted by direct contact with infected secretions or orolabial lesions 2. HSV type 2 - Affects the genitalia and skin below the waist - Direct contact with virus shed from genital lesion or secretions during sexual activity

Answer 117

Patho - Portal of entry (oral cavity, genital mucosa, ocular conjunctiva, breaks in skin) --> cell death and inflammatory response --> vesicles and ulcers --> virus enters nerve endings to sensory ganglia by intraneuronal transport --> herpetic lesions and latent infection --> reactivation in latent neuron --> recurrent infection

Answer 118

Types of infection 1. Primary infection – HSV seronegative (subclinical) 2. Nonprimary, 1st infection – infection caused by a 2nd type of HSV in a person with immunity to 1 HSV type (less severe) 3. Recurrent infection – reactivation of a latent infection in an immune host. Follows stimuli like cold, stress, fever

Answer 119

CM 1. Herpetic gingivostomatitis – most commonly affects 6mos to 5 yo - Drooling, HG fever, refusal to eat/drink, painful ulcers on tongue, gums, and lips - Hallmark: skin vesicles and shallow ulcers that are more extensively distributed than herpangina 2. Herpes labialis/fever blisters/cold sores – most common manifestation of recurrent HSV-1 infection - Most common site at the vermillion border of the lip - Burning pain, itching sensation before appearance of lesions 3. Genital herpes – common in sexually active adolescents and adults - Classic primary genital herpes: local burning and tenderness before vesicles appear - Vesicles become shallow ulcers with yellowish gray exudates, then become crusts 4. Herpes gladiatorum – due to skin trauma and exposure to infectious secretions, commonly in contact sports (wrestling) - Multiple vesicles affect a larger surface area and systemic sx are uncommon 5. Herpes whitlow – HSV infection of the fingers, or toes, involving the paronychia 6. Conjunctivitis/keratoconjunctivitis – usually unilateral, with blepharitis and preauricular LNE - Vesicles on lid margins and periorbital skin with fever 7. Perinatal/neonatal infection – most due to HSV-2 (in utero, SVD, neonatal period. HSV-1 via direct contact - 85% ascending infection - Acquired intrauterine, intrapartum or postnatal a. Intrauterine: § Rash – vesicles, scarring § Eye: chorioretinitis, keratoconjunctivitis § Microcephaly, hydranencephaly § Usually fatal w/ severe sequelae b. Postpartum: a. Disease localized to skin, eyes, mouth b. Encephalitis with or w/o skin, eyes, and mouth ds (D8-17) c. Disseminated infection involving multiple organs (brain, lungs, liver, heart, adrenals, skin) at D5-11 § Septic-like, T instability, irritability, poor feeding, cyanosis, vomiting, respiratory distress, apnea, jaundice, rash (purpuric), seizure, skin, vesicles (75%) --> shock, DIC § 90% die § Severe neuro sequelae 8. HSV encephalitis – acute necrotizing infection affecting the frontal lobe and/or temporal lobe and limbic system - Fever, headache, neck rigidity, nausea, vomiting, seizure, change in sensorium, anosmia, memory loss, expressive aphasia, hallucinations, focal seizures - Untreated infections progress to coma & death in 75%`

Answer 120

Dx 1. Viral C/S – gold standard. Skin/mucocutaneous membrane lesions/surfaces - If mom with genital lesions, do this at 12-24h and tx if C/S(+) or sx’c 2. HSV DNA PCR – test of choice for CSF HSV enceph 3. EEG, cranial CT/MRI – check beyond neonatal period for temporal lobe abnormalities – parenchymal brain edema, hemorrhage, and destructive lesions 4. HSV Ag 5. Tzank smear – characteristic cytologic changes (multinucleated giant cells and epithelial cells with eosinophilic inclusion bodies), rapid dx 6. Cranial CT scan with contrast – focal localization in temporal area with edema and contrast enhancement

Answer 121

Mgt 1. acyclovir 60mkd q8 IV– severe mucocutaneous and disseminated infections in immunocompromised patients, CNS infection, perinatal infection x14s for skin, eyes, mouth ds x21d for disseminated, CNS ds 2. Oral acyclovir 300 mg/m2/dose q8 or valacyclovir – gingivostomatitis, herpes labialis, genital herpes - For 6 mos after tx as suppressive tx

Answer 122

Other Dx tests: 1. CD4+ T cell count – reliable indicator of the current risk of acquiring opportunistic infections - NV: 500-2000 cells/uL - <200/uL = considered AIDS and inc risk of opportunistic infections 2. Baseline studies – to r/o other infections a. PPD testing/ TST then CXR if (+) b. CMV testing/serology c. Syphilis testing (RPR/VDRL) d. Rapid amplification test for gonococcal and chlamydial infection e. Hepatitis A, B, and C serology f. Anti-Toxoplasma Ab g. Ophthalmologic exam 3. Tests prior to antiretroviral tx a. LFT b. Serum chemistries c. BUN, creatinine d. Fasting lipid panel e. Vit B12 and folate levels f. Thyroid function tests

Answer 123

Transmission - Oral secretions and sexual intercourse - Persistent lifelong infection Incubation period: 30-50d Patho - After exposure in the oral cavity, EBV infects B lymphocytes à atypical lymphocytes develop from CD8+ T cells à remains in the host (B lymphocytes) for life - Atypical lymphocytes are characteristic (CD8 T lymphocytes)

Answer 124

CM 1. Infectious mononucleosis - Best known clinical syndrome caused by EBV - 2-4wks - Prodromal period (1-2 wks): Fever (>1 wk), sore throat, generalized LNE, headache, nausea, abdominal pain, myalgia - Triad: fatigue, LNE, pharyngitis - LNE (90%): most commonly anterior and posterior cervical nodes, submandibular a. Epitrochlear LNE suggestive - Hepatosplenomegaly – LUQ abd discomfort and tenderness - Moderate to severe pharyngitis with marked tonsillar enlargement, occ exudates 2. Associated with CA – nasopharyngeal CA, Burkitt lymphoma, Hodgkin ds, lymphoproliferative ds, leiomyosarcoma 3. Ampicillin-rash – morbilliform, vasculitic rash after ampicillin or amoxicillin tx, immune mediated rxn. Selflimited 4. Gianotti-Crosti syndrome – symmetric rash on cheeks with multiple erythematous papules, which may coalesce to plaques and persist for 15-50d. similar to atopic dermatitis, appear on extremities, and butt.

Answer 125

Dx 1. EBV IgM – 4wks to 3mos 2. Elev LFT 3. CBC – elev WBC, atypical WBCs, lymphocytosis

Answer 126

Tx: 1. Supportive – rest, inc OFI, NSAIDs/Paracetamol 2. Avoid contact sports/strenuous athletic activities during 1st 2-3wks 3. CS <2wks – prednisone 1mkd x7d then taper for 7d. - for thrombocytopenia with hemorrhaging, airway obstruction, autoimmune hemolytic anemia, sz, meningitis

Answer 127

Complic: 1. subcapsular splenic hemorrhage or splenic rupture – during 2nd wk, trauma-induced, mild 2. airway obstruction from swelling of tonsils or LNE 3. Alice-in-Wonderland syndrome (metamorphopsia) – perceptual distortions in sizes, shapes and spatial relationships 4. GBS, Reye syndrome Prognosis - Complete recovery - Sx last for 2-4 wk followed by gradual recovery within 2 mos

Answer 128

CH 267/268: ARBOVIRUS CHIKUNGUNYA VIRUS - Mosquito transmitted pathogen (Aedes aegypti, Aedes albopictus)

Answer 129

Patho - Virus replicates in the skin, in fibroblasts, and disseminates to the liver, muscle, joints, lymphoid tissue (LN, spleen), brain à proinflammatory response (cytokines, IL4,10)

Answer 130

Patho - Virus replicates in the skin, in fibroblasts, and disseminates to the liver, muscle, joints, lymphoid tissue (LN, spleen), brain --> proinflammatory response (cytokines, IL4,10) CM 1. Begins 3-7d after bite, acute episode lasts 7-10d 2. HG fever 3. severe joint sx (hands, feet, ankles, wrists) – symmetrical bilateral polyarthralgia or arthritis 4. headache, myalgia, conjunctivitis, weakness 5. maculopapular rash

Answer 131

Dx: 1. Chikungunya IgM – test after >5d infection 2. CBC – lymphopenia, thrombocytopenia (usually >200K) 3. Elev Crea, ALT, AST Mgt: supportive. Hydration and antipyretic tx. NSAIDs for arthralgia

Answer 132

JAPANESE ENCEPHALITIS - Mosquito-borne ds - Vector: Culex tritaeniorhynchus - Native to Asia/Japan to Sri Lanka, inc PH - Usually affect <15 yo, nearly universal exposure by adulthood IP: 4-14d

Answer 133

Patho - Viremia results to inflammatory changes in the heart, lungs, liver, and RES - Virus is neurotropic à neurologic invasion involving large areas of the brain (thalamus, basal ganglia, BS, cerebellum, hippocampus, cerebral cortex) à Virus has direct neurotoxic effects in brain cells and its ability to prevent the development of new cells from neural stem/progenitor cells (NPCs)

Answer 134

CM 1. Prodromal stage (2-3d) – abrupt onset fever, headache, respiratory sx, anorexia, nausea, abdominal pain, vomiting, sensory changes (psychotic episodes) 2. Acute stage (3-4d) 3. Subacute stage (7-10d) 4. Convalescence (4-7wk) 5. Grand mal seizures, parkinsonian-like non-intention tremor and cogwheel rigidity 6. Characteristic: rapidly changing CNS signs (hyperreflexia followed by hyporeflexia or changing plantar responses) 7. Varying sensory status: confusion, disorientation, delirium, somnolence, progressing to coma, maskedlike facial appearance 8. Fatal within 10d

Answer 135

Dx: 1. CBC – nonspecific. Modest leucocytosis in the 2st week then relative leukopenia in the 2nd week, mild anemia, thrombocytopenia in some 2. Dec Na due to SIADH secretion 3. LFT elev Dec Na due to SIADH secretion 3. LFT elev 4. CSF – mild pleocytosis, lymphocytic predominance, protein mildly elev, glu N 5. u/a – albuminuria 6. JE IgM or 4x elev IgG – IgM detected by 4d of sx 7. JE PCR 8. MRI, CT scan: bilateral thalamic lesions with hemorrhage; BS, basal ganglia, pons, SC, cerebellum lesions 9. EEG – diffuse continuous delta slowing, diffuse delta pattern with spikes, theta waves, and burst suppression

Answer 136

Mgt 1. ICU care 2. Seizure control

Answer 137

Prognosis - Fatality rate 24-42% - Highest death in 5-9yo - Sequelae most common in <10yo a. MR, severe emotional instability, personality changes, motor abN, speech disturbance

Answer 138

Prevention 1. JE vaccine – 2 doses IM 0.5ml, 28 d apart (90% efficacy) 2. Mosquito repelling procedures