A Virology 07 Kids Infections

Front 1

Measles Clinical features

Back 1

- respiratory exposure
- 10-14 day incubation
- then 'ratcheting' high fever, cough, coryza and conjunctivitis
- unique red lesions (Koplik's spots) with white centers, appear on buccal mucosa(charicteristic of measles)
- rash first on head and neck

Front 2

Measles Complications

Back 2

- encephalomyelitis
1)Post-infection encephalitis (auto-immune,PIE)
2)Measles inclusion body encephalitis(rare, MIBE)
3)Subacute sclerosing panencephalitis (SSPE)-rare, 7-10yrs after 1o
- 1o measles or giant-cell pneumonia in immunodef
- 2o bacterial pneumonia
- keratoconjunctivitis in kids with nutritional deficiencies

Front 3

atypical measles

Back 3

- in persons who received killed measles vaccine during 1963-1967 then got infected
- atypical rash (no Koplik's), and serious pneumonitis
- no longer use killed vaccine

Front 4

Measels Virus properties

Back 4

- pleomorphic morbillivirus
- one molecule of (-) ssRNA
- a viral-encoded RNA dependent RNA polymerase
- a helical nucleocapsid
- a lipoprotein envelope (know more about spikes)

Front 5

Measels Viral envelope Spikes

Back 5

- one with hemagglutinating (H glycoprotein) activity
- one with cell-fusing (F glycoprotein) activity
- F displayed on infected cell
- Morbilliviruses have NO neuraminidase(N) activity on spikes
- Morbilliviruses induce BOTH nuclear and cytoplasmic inclusion bodies
- F is inactive precursor (Fo) cleaved by host in Golgi
- envelope must fuse to host (via F) to penetrate/infect
- F prot on surf of infected cells, cause cell-cell fusion-> means for cell-cell spread and giant multinucleate cell formation

Front 6

Measels Pathogenesis

Back 6

- inhalation
⇒ RT mucosa
⇒ regional LNs ⇒ primary viremia
⇒ ReticuloEndoth system ⇒ 2o viremia
⇒ lymphoid cells(including skin)
⇒ lesions
- rash from CMI response
- kids' infections probably involve CNS (usually asymptomatic) and growth curve is arrested, but later catches up

Front 7

Measels Immunity

Back 7

- only one serotype
- natural infection produces lifelong permanent immunity
- neutralizing Ab directed at H
- maternal Ab can cross placenta (6 mos protection)
- agammaglobulinemics demonstrate a normal disease course
- cell-mediated immunodef ⇒ persistent infection (w/ complications)
- concomitant depression of CMI to a wide variety of non-measles antigens

Front 8

Measels Epi

Back 8

- most contagious, from aerosolized droplets (sneeze/cough)
- survives in droplets for hours
- infectous from 4 days before rash to 4 days after rash is apparent
- high mortality from lack of adequate nutrition and health care, its immunosuppressive
- only become endemic in conc group of hosts:
1)high rate of contagion
2)no animal reservoir
3)rapidly “burns itself out” in isolated rural areas

Front 9

Measels Diagnosis

Back 9

Clinical symptoms

Front 10

Measels Treatment

Back 10

- no therapy
- A two day course of vitamin A reduces severity in kids
- prevent w/ attenuated vaccine (MMR)

Front 11

Measels Vaccine

Back 11

- give first dose at a min of of 12 months (circulating maternal Ab can inhibit vaccine efficacy)
- give second dose at least 12 months later; usually 4-6 yrs
- window of susceptibility (b/w maternal wearing off and first MMR, or b/w maternal wearing off and 2nd MMR)
- more than >90% covered by age 3

Front 12

Mumps Clinical Features

Back 12

- 18 day incubation
- viremic spread to parotid and presents as swollen salivary glands(characteristic)
- 1/3 infections subclinical
- can involve the epithelial cells of organs(testes, ovaries, kidneys, etc.

Front 13

Mumps Complications

Back 13

- orchitis(Inflamed ball) in 25% of males, worse and more common if post-puberty -> sterility
- aseptic meningitis in up to 50%, usually subclinical, resolves w/o perm damage

Front 14

Mumps Viral Properties

Back 14

- pleomorphic paramyxovirus
- transcription, replication and assembly in cytoplasm like the measles virus
- envelope has 2 glycoprot spikes
- one with BOTH hemagglutinating(H) and neuraminidase(N) activities
- the other w/ cell fusing(F) activity

Front 15

Mumps Pathogenesis

Back 15

- replicates in URT
⇒ LNs which drain the region ⇒ viremia ⇒ replicates in the epith cells of various organs (parotid)
⇒ cell lysis and multinucleated giant cells (cell fusion)

Front 16

Mumps Immune response

Back 16

- only one serotype
- immunity lifelong
- neutralizing Abs directed at the HN envelope protein
- Ab in saliva signals the end of virus excretion
- maternal Ab can cross placenta

Front 17

Mumps Epi

Back 17

- spread via aerosolized droplets, esp in winter and spring
- shed for 7-10 days, beginning 6 days prior to symptoms

Front 18

Mumps Diagnosis

Back 18

- clinical symptoms alone - swollen parotid in mumps susceptable individual
- virus may be cultured
- antiviral Abs may be found in the convalescent serum

Front 19

Mumps Treatment

Back 19

- immunization with live attenuated vaccine (MMR)
- no antiviral therapy

Front 20

Rubella Clinical Features

Back 20

- normally like measles
- 14-21 day asymptomatic incubation
- most cases subclinical
- starts w/ rash (face(slapped) ⇒ extremities) and lasts 3 days(may confuse w/ viral/drug rashes)
- if acquired later in life (by males or non-pregnant females) its uncomplicated
- if pregnant/non-immune, high risk of Congenital Rubella Syndrome or spontaneous abortion
- congenital often results in hearing loss or cataracts
- can take months to manifest
- congenital kids are often persistent carriers and constantly shed infectious virus

Front 21

Rubella Virus Properties

Back 21

- spherical nucleocapsid w/ envelope
- Togaviridae family
- no RNA-dependent RNA polymerase in the virion
- one molecule of (+) RNA
- replication and maturation are confined to the cytoplasm
- infectious virions bud from the cytoplasmic membrane

Front 22

Rubella pathogenesis

Back 22

- aerosolized droplets
⇒ nose and local LN ⇒ viremia
⇒ organs and skin
- no fusion protein, so no cell to cell spread
- viremia! critical for systemic inf
- shed for 1 week after rash cessation
- infection -> lifelong immun
- Abs cross the placenta

Front 23

Rubella Epi

Back 23

- springtime epidemics every few years
- endemic worldwide
- unique among togaviruses b/c it neither infects nor is transmitted by arthropod vector
- outbreaks due to gaps in our vaccine coverage are a concern

Front 24

Rubella Diagnosis

Back 24

- usually clinical symptoms
- tests for immune status of women of childbearing age
- can be cultured in lab

Front 25

Rubella Treatment

Back 25

- vaccination of children
- medical people are often required to be immune
- vaccine is very effective and long-lived(when introduced, 12.5mill cases/yr in US ⇒ 300cases/yr)
- CDC is about to study if vaccine procedure fully eliminates CRS in US

Front 26

Human Herpesvirus 6 and 7 Clinical Features

Back 26

- 6th disease or "roseola" in kids under 2
- high fever and a red rash
- resolves in 3-5 days without complications or sequelae
- most are asymptomatic
- 50% of initial febrile episodes in infants due to HHV-6
- lifelong protection, so 1o infection in immunocompetent adults is rare

Front 27

Human Herpesvirus 6 and 7 Properties of the Virus

Back 27

- replication & structure like other herpesviruses
- icosahedral capsid and spiked envelope
- latent after 1o infection
- 1 case of virus-associated hemophagocytic syndrome (VAHS) from reactivation - prominent phagocytosis of erythrocyts/nucleated BCs in bone marrow and LNs

Front 28

Human Herpesvirus 6 and 7 Pathogenesis

Back 28

- respiratory route ⇒ oropharynx ⇒ many cell types including lymphocytes (esp CD4+ T-lymphocytes), Macs, epi and endo cells
- a tiny fraction of these cells become infected during childhood roseola

Front 29

Human Herpesvirus 6 and 7 Epi

Back 29

- transmitted by salivary droplets
- requires close contact
- infection is universal
- usually presents in infants soon after maternal Ab waned
- most 1o infections are subclinical or febrile illnesses without the rash

Front 30

Human Herpesvirus 6 and 7 Diagnosis

Back 30

clinical presentation

Front 31

Human Herpesvirus 6 and 7 Treatment

Back 31

- no antiviral therapy yet
- but Ganciclovir (GCV) has been via IV to suppress HHV-6 replication in lifethreatening CNS infections in bone marrow recipients
- HHV-6 is more sensitive to GCV than ACV but GCV has more toxic side effects
- no vaccine, but most newborns have maternal Ab
- most infants seropositive by 13 months

Front 32

Parvovirus B19 Clinical Features

Back 32

- 5th disease (age 1-5 years)
- "slapped-cheek" rash and rash on the trunk w/ low fever
- adults asymptomatic or have arthralgia then flu-like
- if hemolytic disorders(SS, thalassemia) -> transient aplastic crisis, from viral impact new erythrocyte prod, combined w/ the reduction in existing ones
- can infect in utero
1) persistently viremic infants w/ severe anemia, so transfusions
2) can cause death (hydrops fetalis)

Front 33

Parvovirus B19 Properties of the Virus

Back 33

- typical parvovirus
- small, no enveloped icosa.
- 1 molecule of + or - ssDNA
- replication and assembly in the nucleus only during S phase
- uses host enzymes
- no integration into host DNA

Front 34

Parvovirus B19 Pathogenesis

Back 34

- narrow specificity for host cells in bone marrow, fetal liver or heart
- directly cytotoxic, rapid killing of host cells(erythropoeitic cells)
- causes high titer viremia w/ bone marrow depression thats short-lived, ending due to the development of Ab
- rash and adult rheumatic syndrome due to immune-complex formation
- infection -> lifelong immun.
- w/o hemolytic disorder->no aplastic crisis

Front 35

Parvovirus B19 Epi

Back 35

- respiratory droplets->URT->bone marrow
- infected spreading virus w/in 5-6 days of infection until sufficient Abs (10-14)
- widely disseminated in community-wide epidemics via school-age children
- can survive pasteurization of blood products

Front 36

Parvovirus B19 Diagnosis

Back 36

- clinical presentation
- isolated cases are commonly misdiagnosed as measles, etc.

Front 37

Parvovirus B19 Treatment

Back 37

- typically not treated
- transient aplastic crisis is readily treated by blood transfusion

Front 38

Coxsackievirus Clinical Features

Back 38

- serogroup A and B (each w/ multiple serotypes)
- can be severe in both kids and adults
- may present as isolated cases or as an epidemic
- infections of NS and URT, LRT, rashes, myocardial disease and conjunctivitis

Front 39

Coxsackievirus Serogroup A

Back 39

1) herpangina
- fever, sore throat, vesicles in oropharynx; acute onset
2) hand foot and mouth disease w/ ulcerative vesicles on buccal mucosa, and vesicular rash on hands and feet
3) aseptic meningitis - typically, uneventful recovery
4) epidemic conjunctivitis - some forms hemorrhagic
5) infantile diarrhea

Front 40

Coxsackievirus Serogroup B

Back 40

1) pleurodynia - acute chest pain and fever - 2-14 days
2) myocarditis and pericarditis - acute and chronic forms, fever, chest pain (due to CTL response)
3) neonatal infection can be inapparent to fatal
- resp and CV involvement
- from the nursery or transplacentally
- associated with juvenile diabetes

Front 41

Coxsackievirus Properties of Virus

Back 41

- typical enteroviruses
- naked, icosahedral
- 1 molecule of (+) RNA
- replication confined to the cytoplasm like polioviruses

Front 42

Coxsackievirus pathogenesis

Back 42

replicates in Oropharyngeal and GI lymphoid tissue
⇒ the RES
⇒ skin, myocardium and CNS

Front 43

Coxsackievirus Epi

Back 43

- fecal-oral mainly, but also inhalation of droplets
- active infection may block poliovirus vaccine
- concurrent enterovirus infections can interfere with replication among each other; one enterovirus infection then dominates

Front 44

Coxsackievirus Diagnosis and Treatment

Back 44

- can be isolated from stool samples, pharyngeal secretions and vesicular fluids
- serum typed for presence of convalescent antibodies
- no antiviral drugs or vaccines available