Herpes (VZV, HSV 1& 2), All Hepatitis viruses, HIV, Dengue, Measles, rubella, Poliomelitis, in!

uen"a, enteroviruses, #apanese en$ep%alitis, prions, viruses t%at

$ause e&ant%ema
Herpes Viruses
o DNA viruses
o infect many animals and man
o 100-180nm diameter, icosahedral capsid, internal core with linear dsDNA, enveloped (ether sensitive)
o replicates in nucleus, buds from nucleus, no virion polymerase
o produce characteristic iant cells and eosinophilic intranuclear inclusion bodies (e!cept "#$)
o viral envelope binds to cell receptors fuse with cell membrane virus uncoats viral DNA enters nucleus viral DNA replicates and transcribed in
nucleus, producin early structural (capsid) proteins viral DNA pac%aed into capsids viral lycoproteins incorporated into the nuclear membrane to
form the viral envelope virions bud out thru nucleus released at cell surface
o early nonstructural proteins (thymidine kinase & DNA polymerase) are different enough from cellular enzymes and targeted by antiviral drugs e.g. acyclovir
o primary infection (acute disease)asymptomatic period (viruses se&uester into sites where they remain in &uiescent latent state) patient e!posed to
incitin aent'due to immuno-suppression viral reactivation (and viral replication) disease
Alpha herpes-viruses(
o )*$1, )*$+, $,$
o primarily infect epithelial cells-
o cause latent infections in neurons-
o cause vesicular rash in both primary infections
and reactivations
o primary infections usually more severe
o have multinucleated iant cells
Beta herpes-viruses:
o ./$, ))$0
o infect and become latent in a wide variety of
tissues
Gamma herpes-viruses:
o "#$, ))$0,1,8
o infect and become latent in lymphoid cells
o ))$2 (#ur%itt3s lymphoma) and ))$8
(4aposi3s sarcoma) are cancer-causin
Alpha Herpes-viruses
)erpes *imple! $iruses(
o cause primary and recurrent diseases
o asymptomatic sheddin of both )*$1and + play an important role in transmission
o virus detectable at cervi!'vulva'anus'urethra in the A#*"N." of ulcers (enital herpes can be transmitted se!ually with a person who3s
sheddin )*$ without symptoms'lesions)
o virus can be cultured from penile s%in'urethra'anus'semen despite absence of symptoms
o pathoenesis(
o entry throuh s%in virus replicates locally 5 epithelial cells of s%in'mucous membranes at the initial site of infection involvement of
lymphatics'the drainin lymph nodes viremia, dissemination (the e!tent depends on the deree of immunocompetence) mirate up the
neuron after primary infectionlatency in the sensory anlion cells
o patholoy(
o vesicular eruption
1
proliferation, balloonin deeneration, acidophilic intranuclear inclusions (areates of viruses in the nucleus)
the vesicles contain serous fluid filled with virus particles and cell debris
multinucleated cells found at the base of lesions
erythema multiforme
recurrent mucocutaneous )*$( more locali6ed, milder symptoms, shorter duration, prodromal sins'symptoms include tinlin and
shootin pains
)*$+ virus'DNA detectable from mucosal surface durin episodes, even prodrome one
o encephalitis
meninitis, perivascular infiltration (as the host responds by causin infiltration of inflammatory cells), neuronal deeneration
o early inclusion
.owdry type A inclusion body
o clinical features
o primary infections usually subclinical
miht be severe in some adults with rash lastin 7-2wee%s
o in non-immune sub8ects, )*$ travels alon sensory nerves to sensory anlia where it persists lifelon in a latent state
durin latency, almost all the viral DNA is located in the cytoplasm and not interated into nuclear DNA
o reactivation 9 virus travels down nerve fibers resultin in lesions, caused by(
reactivation caused by(
immuno-suppression
fever
stress'trauma'sunliht
menstruation'hormonal chanes
lesions rupture virus liberated and transmitted
o both )*$1and+ can cause severe neonatal infections ac&uired A:;"< birth from carriers handlin the child but neither causes conenital abnormalities
o =mmunoloy
o newborns have passive maternal antibodies for 0 months
o neutrali6in antibodies formed after primary infection don3t prevent reactivation due to location of latent virus in immunoprivileed sites
immunity is also type specific and incomplete( reinfection and reactivation occur in the presence of circulatin =>
o ?aboratory dianosis(
o virus isolation (culture) from lesion
specimens from vesicle fluid's%in swab'saliva'tears'corneal scrapins'brain biopsy
scrapins( multinucleated iant cells seen by ;6anc% cell microscopy (cells from the base of vesicle stained with >iemsa)
inoculation of cell cultures(
o .@" of rounded cells in 28-1+hrs, then do neutrali6ation test (N;) or immunofluorescence (=:) with specific antisera
+
both )*$1 and + produce poc%s on chorio-allantoic membrane
both transform hamster cells into malinant cells
o rapid dianosis of encephalitis made by detectin )*$1 DNA in spinal fluid usin @.<
o seroloy(
N; (neutrali6ation of the .@")
in primary )*$ infection, there3s neutrali6in )*$ =/ produced (there3s sinificant rise in antibody titer +-2w%s after
primary infection)
no use in dianosin recurrent infections as there3s already hih levels of e!istin antibodies (no rise in titer in reactivations)
.:;
"?=*A
<=A
=:
o )*$ 1 and + differentiated by(
reactions with )*$1 antiserum and )*$+ antiserum respectively (antiserum consists of antibodies, antito!ins, alutinins)
different rowth patterns at 20de .elsius
different restriction endonuclease patterns of their viral DNA
different viral polypeptides
o treatment(
o acyclovir (acyclouanosine)
it3s converted only by )*$-specific thymidine %inase to the monophosphate (thus low to!icity)
iven =$'oral'topical
indicated for(
=$ for( herpes encephalitis, enerali6ed herpes
oral'=$( enital herpes (shorten duration of lesions, reduce sheddin of virus)
topical( dendritic ulcers, cold sores, enital herpes
prophyla!is in the immunocompromised
treats neonatal infections too
some value for recurrent disease
o valacyclovir ($altre!)
?-valine ester of acyclovir which is converted to active metabolite, acyclovir
reater bioavailability than acyclovir
o for herpetic %eratitis, use(
=do!uridine
;rifluridine (trifluorothymidine)( use topically for )*$-1 eye infections
7
$idarabine (adenine arabinoside)
o no dru treatment of primary infection can prevent recurrences (Drus have no effect on latent state) but prophylactic lon-term administration
of acyclovir'valacyclovir can help suppress clinical recurrences
o epidemioloy(
o infection most common in childhood, another pea% in adolescence
o ubi&uitous human infection( worldwide, humans the only reservoir
o no ma8or communal outbrea%s
o transmission by close contact (with person sheddin virus at mucosal surface or enital'oral secretions)( )*$1(direct contact with oral
secretions eAA %issin), )*$+ (direct contact with enital secretions- se!ually'perinatally)
autoinoculation
intrapartum
o source of transmission 9 cases with herpetic lesions'carriers latently infected with )*$ in secretions
o control of )*$ infections( avoid infected sources'sites, ive acyclovir early in primary infection, vaccines are e!perimental (little value after
primary infection)
)*$ 1 )*$+
@rimary site o ?ips (80B)( primary infections above umbilicus
o )*$1 infections ac&uired in early childhood (almost 100B have
antibodies by adulthood)
o )*$1 ac&uired earlier and more fre&uently than )*$+
o attaches to cell surface at receptor for fibroblast rowth factor
o >enitalia (80B)( primary infections below umbilicus
o )*$+ usually ac&uired after puberty( about +0B of se!ually active adults have
antibodies ()*$+ antibodies correlate with past se!ual activity of
individual'partner)
o )*$+ as a *;D( hiher seroprevalence amon attendees at *;D clinics- hiher
amon homose!uals- closely related to lifetime number of se!ual partners'ae
of se!ual debut'history of other *;Ds)
o fetal'neonatal disease important (s%in lesions and disseminated infections)
Csual site of
latency
o cranial sensory anlia (trieminal anlia) o lumbar and sacral sensory anlia
<outes of
transmission
o respiratory secretions
o saliva
o Doral-enital se! results in )*$1 infection of the enitals and )*$ +
lesions in the oral cavity
o se!ual contact
o perinatal infection
o Doral-enital se! results in )*$1 infection of the enitals and )*$ + lesions in
the oral cavity
*yndromes o acute herpetic gingivostomatitis
o is the commonest primary disease, especially in youn children
(primary disease more severe and lasts loner- recurrences are
innocuous)- many children have asymptomatic primary
infections but symptomatic cases usually in children EFyrs
o genital herpes 9 herpes proenitalis
o se!ually transmitted
o painful vesiculo-ulcerative lesions of the enitalia G penis, perineum,
vulva, vaina, cervi! (lesions more painful and protracted in primary
disease than recurrences)
2
o aphthous stomatits (sores on oral mucosa)
o $incent3s stomatitis (inflammation of mouth)
o vesicles on buccal mucosa, ums ulcerate with rey slouh
(lesions usually heal spontaneously in +-7w%s)
o fever, sore throat, cervical lymphadenopathy, pharynitis,
pharyneal edema, vesicles on mucosa (pharyn!, soft palate,
tonue, floor of mouth)
o fever and to!icity can last for days
o autoinoculation (finers)
o spread mainly by %issin (eAA parent baby)
o differential dianoses( *H*, $incent3s anina, bacterial
pharynitis, herpanina ( an infectious disease, espA of children,
characteri6ed by a sudden occurrence of fever, loss of appetite, and throat
ulcerations, caused by a .o!sac%ie virus)
o recurrent herpes labialis (cold sores)
o lips
o fever (herpes febrilis), blisters, cold sore
o is the commonest recurrent disease from reactivation of )*$ in
trieminal anlion
o crops of vesicles at mucocutaneous 8unction of lips'near nose,
later with painful ulcers
o herpetic whitlow
o vesicles on finers due to implantation of )*$ onto finers due
to contact (in hands of doctors'nurses due to contact with oral
secretions of patients) lesions with serous e!udate
(staphylococcal whitlow has purulent e!udate)
o ec6ema herpeticum, 4aposi3s varicelliform eruption
o superinfection of chronic ec6ematous s%in with e!tensive
vesiculation, fever and sinificant mortality
o %eratocon8unctivitis (eye)
o edema and vesicles of eyelids (lesions of con8unctival
epithelium)( characteristic of herpes
o cornea G dendritic keratitis, ulcers, opacification, blindness Ias
recurrences can lead to scarrin and blindnessJ (don3t ive
steroids as they3re immuno-suppressants)
o aseptic meninitis
o fever, headache, malaise, myalia, tender inuinal lymphadenopathy,
itch, dysuria, vainal'urethral dischare, proctitis (pain, dischare,
tenesmus)
o recurrent lesions from reactivation of latent )*$+ in lumbar and sacral
anlia
o complications of enital herpes( aseptic meninitis, transverse myelitis,
sacral radiculopathy, e!traenital lesions (buttoc%, roin, thih, finer)
o neonatal herpes
o subclinical to severe
o severe enerali6ed infection ac&uired from the infected birth canal of
mother, especially without protective maternal antibodies (serious
neonatal infection espA when mother3s e!periencin primary herpes
because amt of virus produce primary infection a lot more than
secondary, and mothers previously infected can pass =>
transplacentally to protect neonate from serious infection)(
disseminated lesions'encephalitis or milder local lesions at
s%in'eye'mouth
o 8aundice, hepatosplenomealy, thrombocytopenia, lare cutaneous
vesicles
o prevention( caesarian delivery (prior to membrane rupture) for
prenant women with severe enital herpes
o cervical and vulvar carcinoma
o as proven by(
hih fre&A of )*$+ antibodies in patients compared with
matched controls
occasional detection of )*$+ DNA'<NA and antiens in
biopsies (#l == N frament of )*$+ DNA can transform
rodent cells)
o )*$+ may be a hit and run oncoenic virus
o stroner association with human papillomaviruses, espA types 10K18
o aseptic meninitis
o usually mild, self-limitin
)*$ and )=$(
o prior )*$+ infection ris% of )=$ ac&uisition (<<9+-7!)
o )*$ can upreulate )=$ replication rate
F
o acute necroti6in encephalitis
o rare but severe
o sudden fever, headache, confusion
o temporal lobe necrosis
o .*:( lymphocytosis, @.< for )*$ (and treat &uic%ly with =$
antiviral drus)
o brain biopsy( viral isolation, =:
o hih morbidity with neuroloical deficits, hih mortality
o herpetic lesions associated with influ! of .D2 cells( more )=$ on mucosal
surface
o )=$ virions detectable in all enital lesions of persons infected with both )=$
and )*$
o common dissemination to viscera in immuno-compromised patients
(vesicles all over the body, herpes hepatitis etc)
o rare dissemination to viscera in immuno-compromised patients
$aricella ,oster $irus ($,$) .ytomealovirus (./$) "pstein #arr $irus ("#$)
o 1 serotype
o "/ morpholoy L replication cycle similar to )*$
o typical herpes "/ morpholoy
o transforms human'hamster cells in culture
DDcauses widespread infection without %illin host(
o successful due to latency and cell association
(virus spreads from cell to cell directly and thus
neutrali6in antibodies are inefficient- cell
mediated immunity important)
o infection common (widespread seroprevalence),
disease uncommon e!cept in
immunocompromised (neonate, A=D*, transplant)
o "#$ enters # lymphocytes at receptor
site for .7 complement replicates in #
lymphocytes, causin polyclonal rowth
stimulation and lymphoid hyperplasia
o "#$ infection of normal human
lymphocytes results in immortali6ation
(continuously dividin cell line) and
e!pression of nuclear neoantiens ("#
nuclear antien)
o typical herpes "/ morpholoy
;ransmission o epidemic- hihly infectious- respiratory droplets
(hihly contaious childhood disease( M0B have Ab
by ae 10)
o spread via nose and mouth by droplets from
infectious saliva, contact with s%in lesions of
varicella (infectious $,$ in vesicles) and less
commonly 6oster cases
o close contact (urine hand, mouth, se!
o transplacental, within birth canal, breast mil%
o saliva in youn children
o se!ual transmission (semen L cervical secretions)
o blood transfusions, organ transplantations
o there3s proloned sheddin after primary infection'
reactivation
o transplanted %idney (infected alloraft usually, or
leu%ocyte-containin blood products) a source of
./$
o "#$ infections very common( ubi&uitous
in healthy adults who shed "#$ in
pharyneal secretions (NM0B of C* adults
have antibodies)
o close contact O%issin disease3 in saliva of
people with a reactivation of a latent
infection ' people with active infection
o blood transmission is rare
o no ood epidemic described
o sheddin up to 18mths post-recovery
*yndromes( $aricella (chic%en po!)( primary illness
o incubation period 9 +-7wee%s
o $,$ invades mucosa of upper respA tract
o @rimary infection in sero-neative host
o *econdary infection due to activation of latent
infection ' reinfection in sero-positive Oimmune3
infection in early childhood asymptomatic-
fre&uency of clinically apparent infectious
mononucleosis hihest in those e!posed to the
0
replicates in reional lymph nodes primary
viremia ($,$ in reticuloendothelial system)
secondary viremia ($,$ in cutaneous epithelial
cells G po!- can be detected 8ust before rash and up to
+days after rash appears)
o brief prodrome of malaiseLfever (infection at
mucosa of upper respiratory tract which spreads via
blood to s%in) crops of vesicles, later pustules
(papulesvesicles pustulescrusts), appear in
waves, more on trun% than e!tremities (centripetal
distribution) Istarts at trun% then spreads to head and
e!tremitiesJ
o more severe symptoms in adults than children
o itchin common when there3re vesicles
o varicella( lesions at various staes of evolution-
smallpo!( all po! loo% ali%e all at the same stae
,oster (shinles)( recurrent manifestation of infection
o recrudescent disease- occurs in the dermatome of
sensory (dorsal'cranial) nerve anlion due to
reactivation of latent $,$
o painful vesicular eruption morpholoically similar to
varicella (virus present in s%in lesions and
correspondin sensory anlia)
o s%in distribution corresponds to sensory root anlia(
o thoracic (F0B)( belt of roses
o cervical (+0B)
o lumbar (+0B)
o trieminal nerve (1FB)( involvement of
ophthalmic division( iridocyclitis,
%eratits, corneal ulceration
o eniculate anlion( <amsay )unt
syndrome (vesicles in e!ternal auditory
canal, tympanic membrane, anterior
tonue, facial nerve palsy)
o pain can last for wee%s
person
.onenital ./$ infection
o infection of fetus when mum ets a primary
infection (has no Abs to neutrali6e virus before it
can infect fetus)
o fetal infection and damae followin maternal
viremia in any trimester of prenancy
o conenital abnormalities commoner when fetus is
infected in 1st trimester (durin development of
orans)
o primary maternal infection usually asymptomatic
o varied se&uelae( mostly mild, severe in +0B
.ytomealic inclusion disease
o multinucleated iant cells with prominent
intranuclear inclusions( affected orans show
enlared cells with lare intranuclear Oowl3s eye3
inclusions
o infection of the fetus (intrauterine or perinatal)-
leadin cause of mental retardation in the C*
o rare but severe enerali6ed ./$ infection of
infants
o widespread conenital abnormalities( 8aundice,
interstitial pneumonitis, hepatosplenomealy,
thrombocytopenia, hemolytic anemia, neuroloical
se&uelae (microcephaly, periventricular
calcification, chorioretinitis, optic atrophy, mental
retardation, spasticity, epilepsy)
o infected infants can continue to e!crete ./$, espA
in the urine, for many years
@ostnatal hepatitis
o hepatomealy, 8aundice
.lassical ./$ syndrome in a solid oran transplant
virus later in life (eAA collee students)
=nfectious mononucleosis syndrome
o landular fever (may last 12days) and
sore throat
o pharynotonsillitis( typical white
pharyneal e!udates on tonsils- lymph
nodes (usually cervical, sometimes
a!illary'inuinal) K tonsils enlared due
to # lymphocytes proliferatin there
o rash (characteristic after ampicillin)
o incubation period 9 2-1w%s (w%s-mths)
o "#$ demonstrated in # lymphocytes and
epithelial cells in oropharyneal
secretions
o hematoloic( mononuclear cells (NF0B),
atypical lymphocytes (N10B)
o seroloic( transient appearance of
heterophil antibodies, permanent anti-
"#$ antibodies
o most prevalent in seroneative children L
youn adults
o lethary'anore!ia'fever'pharynitis'
e!udative tonsillitis'lymphadenopathy'
hepatosplenomealy'rash e!acerbated by
ampicillin
.omplications of infectious mononucleosis(
o hepatitis (8aundice, abnormal ?:;)
o pneumonitis
o neuroloical (aseptic meninitis,
encephalitis, myelitis, optic neuritis, acute
cerebellar ata!ia, >uillain-#arre
syndrome, peripheral neuropathy, #ell3s
palsy, cranial nerve palsies)
o hematoloical( hemolytic anemia,
thrombocytopenia, splenic rupture
1
o usually occurs lon after childhood varicella, more
fre&uently in old ae 'immunocompromised
recipient( 2-0w%s post-transplant fever, leu%openia,
thrombocytopenia may proress to pneumonitis,
hepatitis new =>, ./$ antienemia (pp0F), ./$
<NA'DNA
myocarditis, pericarditis
Differential dianoses of =/*( streptococcal
pharynitis, primary )=$ infection, ./$
infection, acute to!oplasmosis
.omplications $aricella(
o superinfection of s%in by bacteria (staphylococci '
streptococci) [sec. infections as lesions arent kept
clean! give antihistamines"calamine lotion to prevent
scratching as hands have lots of bacteria#
o aseptic meninitis
o neuroloical syndrome
o reional lymphadenitis, abscesses
o <eye3s syndrome (encephalopathy and liver
deeneration, associated with $,$ K influen6a #
infections, aspirin in children)
o post-infectious encephalomyelitis (1w% after rash) in
the immunocompromised, meninoencephalitis,
cerebellar ata!ia
o pneumonia (couh, dyspnea, hypo!ia, diffuse
nodular infiltrate, pulmonary calcification,
potentially fatal)
o hemorrhaic (fulminatin varicella)(
thrombocytopenia, D=$.
o arthritis
o conenital varicella (rare transplacental infection in
neonates born to mothers with varicella in early
prenancy)( rare as NM0B of women of child-bearin
ae have antibodies- intra-uterine death possible at
any time- conenital varicella syndrome at 1st and
+nd trimester (s%in lesions, limb hypoplasia, eye
disease, neuroloical defects)
o neonatal varicella( child contracted disease from
mother near time of delivery when there3s little'no
protection from maternal antibodies (hih mortality
in severe disease)(ris% of death 7FB
o overwhelmin varicella( in immunosuppressed
*yndromes caused by ./$ (continued)(
=nfectious mononucleosis syndrome
o spontaneous in otherwise healthy youn adults
o post-perfusion syndrome'after open heart surery
o clinically similar to landular fever (by "#$) but
less pharynitis and lymphadenopathy
o mild hepatitis
o circulatin atypical lymphocytes (./$
mononucleosis)
o heterophil-neative (no heterophil antibodies)
o ./$-uria (in %idneys, e!creted in urine)
o ./$ isolation from @#? (peripheral blood
lymphocytes)
=nfection in the immunocompromised host(
o due to cytoto!ic, radiotherapy, cancer, oran
transplantation, A=D*
o primary infection with oran transplant or blood
transfusion
o in A=D* patients, ./$ commonly infects
intestinal tract and causes intractable diarrhea, or
causes retinitis that can lead to blindness
o immunocompromised state could lead to
recrudescence followin reactivation of latent
infection (mild to severe, dependin on deree of
immunosuppression)
o ./$ pneumonitis, hepatitis
o disseminated ./$( fever, leu%openia,
pneumonitis, hepatitis, colitis, retinitis
>uillain-#arre syndrome
)airy leu%opla%ia
whitish, non-malinant lesion on tonue (espA
in A=D* patients)
Nasopharyneal .arcinoma
o stronly associated with "#$
o N@. cells have interated "#$ DNA and
"#$ mar%ers
o hih anti-"#$ antibodies in N@. than
controls (eAA => and =A to viral capsid
antien)
=mmunoblastic lymphoma
o lymphoproliferative disorder in patients
with hereditary impaired cell-mediated
immunity (hereditary immunodeficiencies
and ac&uired immunosuppression eAA
iatroenically induced in oran transplant
recipients)
o polyclonal immunoblastic proliferation,
then monoclonal neoplasia
o mostly e!tranodal
.hronic fatiue syndrome
o e!treme fatiue, fever, sore throat, painful
lymphadenopathy, muscle wea%ness,
memory loss
o reactivation of latent "#$ infectionP
D"#$ remains latent in # lymphocytes- a few
copies of "#$ DNA interated into cell
enome- many copies of circular "#$ DNA
8
patients (conenital'ac&uired immune deficiency)
,oster(
o encephalomyelitis- lymphocytic pleocytosis in .*:
o post-herpetic neuralia (can be debilitatin), usually
in elderly
o disseminated 6oster( vesicles outside the involved
dermatomes too, in the immunosuppressed
$%& infection causes an immunosuppressive effect by
inhibiting ' cells [maintains latent state by making the
%($ class )*viral peptide comple+ unstable and thus
viral antigens are not displayed on the cell surface#
(circulating antibodies and cell*mediated immunity
usually protect)
found in cytoplasm
.omplication( #ur%itt3s lymphoma K other #
cell lymphomas (cancers of lymphoid oriin)
o in areas with holoendemic malaria in
tropical Africa
o persistent malarial infestation have
immuno-suppressive effect on cytoto!ic ;
lymphocyte surveillance of "#$-
malinant transformed cells
o #-lymphocyte cells e!press "#$ mar%ers
(eAA "#$ DNA)
o characteristic 812'+++ chromosomal
translocation, leadin to dereulation of
.-myc oncoene
=mmunoloy o previous infection with varicella confers life-lon
immunity to varicella but not to 6oster (fre&A of
6oster with advancin ae due to wanin immunity)
o 6oster is a reactivation of latent $,$- occurs in
persons with immunity to varicella too
o antibodies present in most humans e!cept youn
children without ./$
o ./$ secreted in urine even in the presence of
serum neutrali6in antibodies
DDviral capsid antien ($.A) $.A =>
permanent but titers hih from the start- $.A
=/ sensitive K specific for acute infection
DD"# nuclear antien ("#NA) Ab appears late
in course and persists for life
DDearly antien diffuse( anti-D Ab pea%s 7-
2w%s after onset, positive in N@.
DDearly antien restricted( anti-< Ab
uncommon in =/*, positive in #ur%itt3s
Dianosis o usually made clinically
o ;6anc% smear of scrapins of swabs from base of
lesions( multinucleated iant cells (for presumptive
dianosis)
o =:( intracellular viral antiens
o "/ to distinuish from po!viruses
o >el diffusion usin specific antisera to detect )*$,
$,$, $$ antiens
o definitive dianosis( virus isolation in fibroblast
cultures (focal .@") L =:, N; of isolate with specific
antisera
o seroloy( .:'N;'=:'"?=*A
o virus isolation
o from urine'throat swab
o human embryo lun cultures
o slow characteristic .@" of foci of
swollen cells and intranuclear owl3s
eye inclusions after +-7w%s
o multinucleated iant cells formed
o viral detection
o des&uamated cells in urinary
sediment
o owl3s eye inclusions
o "/, viral antien, DNA (@.< assays
o hematoloic dianosis( absolute atypical
lymphocytosis (as many as 70B abnormal
lymphocytes seen on as smear) Ithese
atypical lymphs are cytoto!ic ; cells
reactin aainst "#$-infected # cells( are
lare'have lobulated nucleus, vacuolated
basophilic cytoplasmJ- atypical
mononuclear cells- (at least 10B)
o heterophile antibodies (@aul-#unnell test)
are hemalutinatin antibodies to
sheep'bovine'horse- the antibodies
removed by absorption with o! <#. but
M
o =/ in both recent varicella and 6oster
o rise in Ab titer in varicella useful in
dianosis
o hih levels of neutrali6in Ab in 6oster
already
to detect ./$ DNA'<NA in
tissue'body fluids eAA spinal or
amniotic fluid)
o ./$ =>'=/ (2-fold rise indicates recent
infection)
o seroloy( N;, .:;, <=A, =:, "?=*A (=/, =>)
o blood culture, urine culture (non-specific)
not with uinea pi %idney- present in
M0B- hetrophil antibody test can dianose
=/ early since it3s positive by wee% + but
antibody titer declines post-infection
(after 0mths) thus can3t detect prior
infection- monospot screenin test to
detect the heterophil antibodies as it3s
more sensitive K specific and less
e!pensive than tube alutination tests
o M0B of healthy adults have "#$ Ab G
"#$ =/ useful confirmation for =/-
antibodies to "#$ antiens(
;reatment o no antiviral therapy indicated for chic%en po! '
6oster in immunocompetent children
o immunocompetent adults treated with acyclovir to
reduce duration and severity of symptoms
o if symptomatic( antipyretics, antipruritics
o varicella-6oster immune lobulin ($,=>) for
prophyla!is (ive within M0hrs of contact with an
infected person) in hih-ris% immunocompromised
children, seroneative prenant women, newborn
infants e!posed to maternal varicella
o acyclovir for severe varicella pneumonia' hepatitis'
encephalitis' hemorrhaic varicella
o acyclovir can help limit proression of 6oster'
varicella'disseminated disease if iven early, even in
the immunocompromised (definite benefit) G stops
viral replication, compensates for delayed specific
immunity
o acyclovir for trieminal nerve'disseminated 6oster
o immunocompromised children with varicella (those
with chronic diseases'on courses of
steroids'salicylates)
o no treatment re&uired for immunocompetent hosts
o >anciclovir'valanciclovir for life-threatenin
./$ infections (retinitis, colitis, pneumonitis) in
immuno-compromised patients)
o control(
o isolate newborns with severe ./$
infections (as these infants shed the
viruses in urine)
o screen oran'blood donors and
recipients (should be ./$ antibody
neative)
o ./$ = prophyla!is in ./$-
seroneative oran recipients
receivin orans from seropositive
donors
o live ./$ vaccine underoin
clinical trials
o symptomatic
o no antiviral therapy needed for
uncomplicated =/-
o acyclovir little activity aainst "#$ but
hih doses useful in life-threatenin "#$
infections
o avoid ampiciillin
o "#$ underoin clinical trials
,heterophil antibodies dont react -ith any
component of ./& (./& infection probably
modified modifies a cell membrane
constituent such that it becomes antigenic and
induces the hetrophil antibody) 0 not specific
for ./& infection (also seen in (ep. / and
serum sickness)
"pidemioloy o worldwide, sporadic, no seasonal distribution
o 6oster mainly in adults, not ac&uired throuh contact
o usually asymptomatic in healthy hosts (NF0B of
adults have ./$ Ab)
o worldwide, usually subclinical in children
o limited host rane( # lymphocytes,
10
with 6oster cases as $,$ is absent from upper
respiratory tract
o 6oster may sometimes ive rise to varicella outbrea%s
o control( barrier-nursin and isolation of
immunosuppressed patients, $,=> prophyla!is,
$aria! for hih-ris% patients
o $accine with live attenuated $,$ ($aria!)( effective
in preventin varicella in children'6oster in adults but
doesn3t eliminate the latent virus
o infection of immunocompetent children'adults
usually asymptomatic (subclinical) ./$ enters
latent stae in various tissues eAA circulatin
leu%ocytes'%idneys reactivated when cell
mediated immunity reactivation in cervical
cells result in an infected birth canal
o virus sheddin in saliva'tears'urine'semen' cervical
secretions'breast mil%
o e!cretion rate and Ab titers increased in immune
deficiency induced by immunosuppressive aents,
prenancy, debilitatin disease
nasopharyneal cells
o
))$ 0 ))$ 1 ))$ 8
o human #-lymphotropic virus (infects both # and ; cells and remain
latent there- reactivated in those immunocompromised)
o oriinally isolated from patients with lymphoproliferative disorders
o can row in vivo in many types of cells
o healthy individuals have antibodies and ))$0 in oral secretions (80B of
population seropositive)- most humans seropositive by +yrs
o + subtypes A and # (can3t differentiate seroloically)
o isolated from .D2
; cells
o seroconversion in
most children
o virus persists in
saliva of 1FB of
normal adults
o no association with
human disease so
far
o viral DNA detected in saliva'semen' peripheral
mononuclear cells
o mechanisms of tumor development un%nown
o se!ual transmission ' throuh transplants (eAA of
%idneys)
.linical
features
o eanthem subitum (roseola infantum)( viral disease of infants and
youn children (0mths-7yrs) (miht be confused with rubella)
o incubation period( 1-+w%s
o abrupt onset of hih fever, lymphadenopathy, convulsions (febrile
sei6ures), mild sore throat
o rubelliform rash (pin%ish rash all over e!cept face) after the fever
disappears (a few days) that lasts for hrs-days
o leu%openia (abnormally low Q#. count) with relative lymphocytosis
("#$-like syndrome!
o 4aposi3s sarcoma
o 4* lesions virtually all ))$8-positive by @.<
o N+0000 times more common in persons with A=D*
(NMFB of )=$-associated 4* in homose!ual men)
o 4* in A=D*( malinancy of vascular endothelial cells
- 1 or more vascular purple nodules in the s%in,
mucous membranes, viscera (lun and biliary
system), oral cavity, >=;
o endemic form( indolent and of little pronostic
11
o spontaneous recovery
o manifestations in the immunocompromised
o ))$0 in the transplant patient( pneumonitis, encephalitis, bone marrow
suppression
sinificance
o in A=D* patients( uncommon aressive #-cell
lymphoma presentin as lymphomatous effusions in
pleural, pericardial or peritoneal cavities
o in advanced A=D*, it3s less important a cause of
morbidity'mortality than opportunistic infections
Dianosis o ))$0 in serum and throat washins durin pyre!ia o o biopsy of s%in lesions but not rown in culture
;reatment o anti-pyretic aents to control fever o o no antiviral ' vaccine
o surically e!cise'radiation'systemic alpha-interferon
/easles /umps <ubella
o paramy!ovirus( ss<NA(-), enveloped, helical
o 1 serotype
o worldwide, outbrea%s every +-7yrs
o A=D* patients, children, population that hasn3t
e!perienced measles most susceptible
o neutrali6in antibodies aainst hemalutinin
o paramy!ovirus
o 1 serotype
o neutrali6in antibodies
aainst hemalutinin
o worldwide, pea% in winter
o 70B of children have
subclinical infection
which confers immunity
o non-arthropod borne virus of the ;oavirus family, enus
<ubivirus
o 1 serotype
o small ss<NA(L), enveloped, icosahedral
o neutrali6in antibodies aainst hemalutinin
o worldwide, epidemics every 0-Myrs if no vaccine
;ransmission o aerosol (respiratory droplets) by couhin'snee6in
durin prodrome and a few days after rash appears G
e!tremely contaious
o respiratory droplets o respiratory droplets- moderately infectious
o transplacental
@athoenesis o cells of upper respiratory tract infected virus enters
blood reticuloendothelial cells infected virus
spreads to s%in via blood rash due to cytoto!ic ;
cells attac%in vascular endothelial cells in s%in that are
infected with measles L due to antibody-mediated
vasculitis virus can3t be recovered after rash appears
(can3t spread rash to others)
o cells of upper respA tract
infected spreads
throuh blood parotid
lands, testes, ovaries,
pancreas, menines
affected
o viral replication in respiratory epithelium, nasopharyn! and local
lymph nodes spread via blood (viremia) to internal orans and
s%in rash probably due to antien-antibody mediated vasculitis
o recurrent sprin endemics with increase in susceptible population
in pre-vaccine era and countries without vaccination
o 1M02 epidemic in C*A( + million cases with 7A0B of prenant
1+
o there3re multinucleated iant cells due to the fusion
protein in the spi%es
women involved (+000 victims of conenital rubella syndrome)
=ncubation
period
o 10-12days (viremia, virus replication in respiratory
epithelium and s%in G measles rash)
o +-7 wee%s o +-7 wee%s
.linical
features
o ubi&uitous common infection of early childhood
(infection by Fyrs without vaccination)
o incubation prodrome of
fever%con&unctivitis%rhinorrhea%cough specific
symptoms( 'oplik(s spots (pre-rash- dianostic briht
red lesions with central white dot on buccal mucosa)
around parotid duct orifices herald onset of rash
typical maculopapular rash (flat L palpable)
appears a few days later as the fever subsides, from
face and spreadin to the entire body includin palms
and soles there3s discoloration after the rash has
disappeared (post-measal hypo'hyper-pimentation)
o atypical measles in people iven %illed vaccine and
subse&uently infected with measles virus( atypical rash
without 4opli%3s spots
o measles in prenant woman increased ris% of
stillbirth, not conenital abnormalities (measles more
serious than rubella fetal infection( measles causes fetal
death, rubella causes conenital abnormalities)
o measles usually subsides within 10days from onset in
immunocompetent
o most infections aeF-1F
o incubation prodrome of
fever' malaise'anore!ia
unilateral' bilateral
tender swellin of parotid
lands (increased pain
when drin%in citrus
8uices), salivary land
enlarement, pain
aravated by eatin,
sometimes presents as
toothache, tender cervical
lymphadenopathy
o unilateral swellin
obliterates the anle
between 8aw and nec%
o no rashR
o usually benin, resolvin
spontaneously within 1
wee%
<ubella (>erman measles)
o mimics measles but it3s milder and shorter
o common viral e!anthem
o usually subclinical, espA in children
o constitutional symptoms usually mild and variable
o incubation prodrome of malaise, headache, fever, con8unctivitis,
cory6a, couh, posterior auricular lymphadenopathy
occasionally, discrete rose spots on palate (:orschheimer3s
spots) herald onset of s%in rash typical rubella rash( small
maculopapular lesions startin from face, proressin to trun% and
e!tremities), lasts about 7days- tender lymphadenopathy
(fre&uently suboccipital'postauricular'cervical nodes)
o in adults, espA women, they can be polyarthritis caused by immune
comple!es
.omplications(
o arthralia (8oint pain), arthritis (8oint pain AND inflammation)-
affects 1 or more lare and small 8oints when rash subsides eAA
%nees, wrists, finers, fever
o encephalitis (uncommon, in adults more than children, sometimes
fatal)
o purpura (bleedin in s%in)- thrombocytopenia with'without
hemorrhae
.omplications Din the malnourished'immunocompromised (famine L
measles 9 hih mortality)
o mucosal infections (con8unctivitis, otitis media at
middle ear G bacterial)
o respiratory( bronchopneumonia, iant cell pneumonia
(rare proressive measles lun infection( iant cell
clusterin compromises lun function)
o G"( diarrhea due to measles virus ' secondary bacterial
infection
Din adults more fre&uently
o aseptic meninitis
(relatively common but
mild) G also caused by
co!sac%ievirus'echovirus-
headache, photophobia,
stiff nec%
o orchitis (testes)
o pain and
)ongenital *ubella $yndrome
o teratoenic to fetus particularly if intrauterine infection of mother
occurs durin 1st trimester of prenancy
o rubella virus crosses placenta invades and damaes almost any
fetal oran
o ris% and e!tent of embryopathy reater espA durin earlier periods
of oranoenesis (77B in 1st month of prenancy, +FB in +nd
month, MB in 7rd month, 2B in 2th month)
o stillbirth, spontaneous abortion
17
o +eurological(
o post-infectious demyelinatin encephalitis
with hih mortality and permanent se&uelae
eAA deafness, mental retardation
o sub-acute sclerosin panencephalitis (**@")(
possibly due to persistent latent infection of
neurons by defective measles virus ' abnormal
immune response to measles ' impaired host
immunity- develops lon (mths-yrs) after
apparent recovery- rare but fatal
o myoclonic sei6ures, intellectual deterioration,
suppression-burst ""> pattern (low voltae
interrupted by periodic hih voltae
comple!es), rapidly fatal
o cytoplasmic inclusions in neuronal cells
o multiple sclerosis
swellin
o in 10-+FB of
post-pubertal
cases
o usually unilateral
(bilateral leads to
subfertility)
o pancreatitis in 10B of
adults
o rare( myocarditis'
nephritis' oophoritis'
thyroiditis'demyelinatin
encephalitis'arthritis
o permanent defects include( ocular lesions (cataract( opa&ue cornea,
retinopathy, microphthalmia), ear (sensorineural deafness), .N*
(microcephaly, mental retardation, spasticity)
o cardiorespiratory system G heart malformations, @DA, $*D,
pulmonary stenosis, interstitial pneumonitis
o diabetes mellitus( insulin dependent due to infection of islet cells
o hepatosplenomealy, thrombocytopenia (rash that doesn3t blanch),
bone-metaphyseal osteitis
o some children infected in utero can continue to e+crete rubella for
months follo-ing birth 0 public health hazard! some congenital
shedders are asymptomatic and -ithout malformations. only
diagnosed -hen virus is isolated and -ith high 1g% titers and
persistent 1g2 long after maternal antibodies have disappeared
=mmunity o life-lon immunity
o => neutrali6es virus durin viremic stae but cell-
mediated immunity more important
o maternal antibodies crosses placenta protection in
first 0 months
o life-lon immunity
o mumps only occurs once
(other cases of parotitis
caused by other viruses
eAA parainfluen6a,
bacteria'duct stones)
o life-lon immunity
o antibody can cross placenta to protect fetus
o &uarantine infected individual, screen all surroundin family
members, e!posed contacts and hospital personnel
o screen all prenant women antenatally for rubella antibodies (L
)ep # and )=$) in case vaccination wasn3t effective
o specific serum = may be protective if iven early after e!posure
o life attenuated rubella vaccine (the //< vaccine)( current strain
developed in human diploid cells
o vaccinate both se!es at ae 1+, vaccinate women of childbearin
ae
Dianosis o tissue culture from virus isolated from
pharyn!'con8unctiva'urine - infected mon%ey %idney
cells demonstrate multinucleated iant cells
o seroloy( measles =/ assay for recent infection-
measles => for retrospective dianosis (use rise in
titer of 2fold or more for difficult cases)
o tissue culture in mon%ey
%idney cells ' )e?a cells '
hen3s es- specimens
from saliva'throat
washins' urine' .*:
o .@" effect( roundin of
cells, multinucleated
syncytial formation,
eosinophilic inclusions
o tissue culture but virus isolation is time-consumin
o seroloy( detect 2fold or more rise in antibody titer and'or =/ for
up to 1month after rash (observe presence of =/ in a sinle
acute-phase serum sample)
o standard test( hemalutination inhibition (see if the <#.s in the
sample lose the ability to clump toether when the antibody to the
virus is added)
o "?=*A
o radial hemolysis in el
12
o can hemalutinate chic%
<#.s
o seroloy( =/' =>' .:;'
)=' N; (2-fold antibody
titer rise in these tests is
dianostic)
o =:
o passive alutination
o <=A (radioimmunoassay)
o part of the ;S<.)"* => panel (to!oplasma, rubella, ./$,
herpes, syphilis)
o if a pregnant -omans e+posed to rubella3 1g% presence indicates recent
infection ()45 or greater titer of 1g2 indicates immunity and conse6uent
protection of fetus)! an amniocentesis can reveal -hether there is rubella
virus in amniotic fluid
;reatment o no antiviral therapy available o no antivral therapy o no antiviral therapy
=mmuni6ation( live attenuated //< vaccine
o administered subcutaneously at ae 1 (earlier in poorer communities)- *inapore at 1Fmonths
o effective L lon lastin immunity (at least 10yrs)
o mild pyre!ia but serious complications are rare
o NS; iven to immunocomprmised'severely malnourished children and prenant women
o if iven to unimmuni6ed youn adult women, they must not be prenant and must use contraception for the ne!t 7 months
o passive immuni6ation with immune ammalobulin for contacts with immunodeficiency eAA leu%emia
o recommended for unimmuni6ed pre-adolescents who have not had mumps parotitis
o induces some respiratory =A which can limit spread of the virulent virus by nasal carriae
o //< for both se!es to establish herd immunity and to prevent viral spread
o adverse effects of vaccine( fever, rash lymphadenopathy, arthralia, polyneuropathy (rare)
"nfluen,a A, B, ) (-rthomyoviruses! *espiratory $yncytial Virus (.aramyovirus! .arainfluen,a (.aramyovirus!
o soluble (s) antien is the group-specific antigen that determines A'#'.( found in
ribonucleoprotein core internally- same s A shared by all influen6a A viruses-
.:;
o )emalutinin is the type specific antigen( is the main neutrali6in antien
responsible for host immunity (hemalutinin and neuraminidase are the type-
specific antiens on the surface)
o nucleocapsid has 8 discrete ss<NA(-) sements randomly incorporated into
virion durin maturation, helical capsid, enveloped (lipoprotein), 100nm
o has 7 types of virion <NA polymerase (which is <NA-dependent <NA
polymerase)( transcribes the (-)ss<NA into m<NA (the enome isn3t infectious)
o NS iant cell formation
o envelope covered with radially-pro8ectin lycoprotein surface pro8ections(
hemalutinin K neuraminidase on different spi%es
Dhaemagglutinin (the taret of neutrali6in antibodies)G spi%es for virus attachment
to host cells- type'strain-specific antiens (antienic variation thru constant mutations
to escape Abs)- alutination of various animal erythrocytes G inhibited by antibodies
PARAMYXOVIRUSES
o measles
o mumps
o respiratory syncytial virus
o parainfluenza
o NS hemalutinin ' neuraminidase- has fusion
protein on surface spi%e only
o the most important cause of pneumonia and
bronchiolitis in infants
o an important cause of otitis media (inflammation
of middle ear( pain, di66iness, impaired hearin)
in children, pneumonia in elderly and those with
chronic cardiopulmonary diseases
o iant cells formed
o 1 serotype
o humans K animals both infected
but the animal strain doesn3t
infect humans
o replication similar to measles
o worldwide disease espA in winter
months
o main cause of croup in children
youner than F
o most infections ac&uired by ae F
o iant cells formed

1F
(hemalutinin inhibition)
Dneuraminidase 7 a protein that cleaves neuraminic acid to release progeny virus
from the infected cell- it acts on neuraminic acid receptors- it helps virus to spread and
it mutates rapidly- it also derades protective layer of mucus at respiratory tract,
enhancin virus3 ability to infect the respiratory epithelium- there3re neuraminidase
inhibitor drus
Antigenic Variation:
Antigenic shift(
o such variants occur every 10-+0years
o due to recombination of <NA sements of + antienic types (from different
animal viral strains eAA swine, duc%, wild birds, human) that simultaneously
infect the same cell Ientire sements of <NA are e!chaned eAA at the farmer3s
respA tract and they each code for sinle proteins eAA hemalutinin- may have
human A virus bearin the avian virus hemalutininJ
o ma8or antienic chane of both hemalutinin and neuraminidase
Antigenic drift(
o spontaneous mutations in <NA enome leadin to minor chanes in
hemalutinin- variants occur early
Depidemics and pandemics occur when the antienicity of the virus has chaned
sufficiently such that pree!istin immunity in people is no loner effective
Dantienic desination accordin to serotype of hemalutinin ()) and neuraminidase
(N) eAA )+N+ (Asian flu), )7N+ ()4 flu), )FN1 (avian influen6a flu- bird flu)
o )FN1 primarily causes avian flu in chic%en and an aressive human influen6a
from direct infection of humans from chic%ens (personperson transmission still
rare but possible if there3s ressortment with human-adapted strains)
o )FN1 has reat virulence as it3s resistant to interferon, leads to increased
production of cyto%ines that mediate the pathoenesis of pneumonia and acute
respiratory distress (A<D*)A )FN1 sensitive to neuraminidase inhibitors,
oseltamivir (;amiflu), ,anamivir (<elen6a)
PARAMYXOVIRUSES:
o envelope !elical non"se#mente ssR$A%"&'
()*nm
o #enetic recom+ination oesn,t occur
o envelope: envelope covere -it! .types of
surface spi/es:
o 00t!e (st surface spi/e contains !ema##lutinin
123 an neuraminiase 1$3 on t!e same spi/e
o 00t!e .n surface spi/e 4 fusion protein 153
t!at causes cell fusion an sometimes
!emolysis %5 meiates formation of
multinucleate #iant cells %syncytia&
o 0000anti+oies to 2 or 5 protein neutralizes
infectivity
o !as virion R$A"epenent R$A polymerase
t!at transcri+es ssR$A%"& into mR$A %#enome
isn,t infectious&
(refer to previous column)
/ serotypes:
Dtypes distinuished by antienicity,
cytopathic effect, pathoenicity
D types 1K+ are ma8or causes of croup
Dall 2 serotypes cause upper K lower
respiratory tract disease without
viremia
o 0ype 1: .roup in infants
o 0ype 2: "pidemics (winter)
o 0ype 3: bronchiolitis and
bronchopneumonia in youn
infants- croup in older infants
o 0ype /: minor respiratory
infection (rarely causes disease
e!cept common cold)
"nfluen,a A
o causes worldwide epidemics IpandemicsJ every 10-+0years
"nfluen,a B
o causes ma8or outbrea%s- periodic epidemics
o it3s only a human virus (no animal source of new <NA sements- thus no
antienic shifts but does undero antienic drifts G thus the current strain due to
antienic drift must be included in yearly influen6a vaccines)
"nfluen,a )
o less common- causes mild respiratory tract infections but no outbrea%s
o causes outbrea%s in hospitali6ed infants too
(controlled by handwashin and loves)
o outbrea%s of respiratory infections worldwide,
espA in winter, almost everyone infected by 7yrs
;ransmission o airborne respiratory droplets o respiratory droplets
10
o direct contact of contaminated hands with
nose'mouth
=ncubation o 1-2days o
.linical
features
o a ma8or epidemic disease with occasional pandemics
o incubation abrupt onset of fever'myalia'malaise' headache rhinorrhoea,
snee6in, dry couh, sore throat
o viral multiplication in respiratory epithelium with des&uamation (the infected
epithelial cells die and des&uamate) and ciliary damae
o symptoms usually resolve in 2-1days easily
o lower respA tract diseases
o commonest cause of bronchiolitis in youn
children
o pea% at 7 months (durin winter)
o fever, couh, dyspnea, tachypnea, whee6in,
cyanosis, inspiratory indrawin
o febrile common cold G sore throat,
couh, hoarseness
o #ronchiolitis (bronchitis,
larynitis, otitis media,
pharynitis
o #ronchopneumonia
.omplications @neumonia
o (usually in winter months, a lot of deaths with bacterial pneumonia that3s
secondary to influen6a)
o primary viral (rare but hih mortality)( respA failure eAA bird flu infects luns
directly with rapid death within 28-1+hrs)
o secondary bacterial infection after damae of bronchial mucosa (strepA
pneumoniae, haemophilus influen6ae, staphA aureus)- antibiotics indicated-
o in( e!tremes of ae, immunocompromised, chronic cardiorespiratory diseases,
chronic smo%ers (as their epithelium is replaced by non-ciliateds&uamous cells
/yocarditis( infection of myocardium
/yositis( inflammation of muscles followin myalia
<eye3s syndrome
o associated with viral infections eAA influen6a #' chic%enpo! and aspirin inta%e
(iven to relieve fever) in children
o cerebral edema (encephalopathy), liver fatty deeneration, hih mortality
.linical features (continued)
o in elderly (N0F) and adults with chronic
cardiopulmonary diseases, <*$ causes severe
lower respA tract disease includin pneumonia
o severe pneumonia may result from reaction
between virus and maternal antibodies( immune-
mediated (immune comple!es) and'or
mechanical obstruction of narrow bronchioles by
inflammatory process (narrowed lumens lead to
whee6in)- immune comple!es may damae
respA tract cells
.omplications
o secA bacterial infections, otitis media, cardiac
failure, apnea (*CD*, cotbaby syndrome)
o up to FB mortality in bronchiolitis and
pneumonia
o hih mortality associated with .N*
malformations and conenital diseases of
heart'lun
.roup (NS; complication)
o acute larynotracheobronchitis
(the entire upper respA tract)
o couh, hoarseness
o if severe, there3s dyspnea, stridor,
cyanosis and may re&uire
tracheostomy (lumens in infants
very small( severely narrowed
when inflamed)
o croup 9 condition of the
laryn!'trachea characteri6ed by a
hoarse couh and difficulty in
breathin
o differential dianoses( diphtheria,
)aemophilus influen6ae,
epilottis
@athoenesis o virus inhaled neuraminidase derades mucus of respA tract virus ains access
to cells of the upper and lower respiratory tract Inecrosis of superficial layers of
respiratory epitheliumJ (locali6ed infection- viremia seldom occurs)- systemic
symptoms are due to cyto%ines in the blood
o <*$ infection in infants more severe- involves
lower respA tract Iupper respA tract infection in
older children and adults( milder as lumens are
now bier, not easily constrictedJ
=mmunity o secretory =A in respA tract
o cytoto!ic ; cells are protective
o => produced too but less protective
o antibody aainst hemalutinin neutrali6es infectivity to prevent disease but
antibodies aainst roup-specific antiens that are located internally don3t
prevent disease- antibodies aainst neuraminidase don3t neutrali6e infectivity but
o antibodies to : protein neutrali6es infectivity
o most have multiple infections caused by <*$
(incomplete immunity)- not due to antienic
variation- =A fre&uency of <*$ infections
with ae
o antibodies to ) or : protein
neutrali6es infectivity
11
does disease by amt of virus released from infected cell
Dianosis o virus isolation usin chic% embryo, mon%ey %idney cells (no .@" but there3s
hemadsorption)- typin by )- virus isolated from nasal'throat washins and
swabs, sputum
o =: of antien in respiratory epithelial cells
o seroloy (.:; or )=)( rise in antibody titer at least 2! in paried serum samples
ta%en early and 10days later
o tissue culture ()e?a cells')ep-+ cells)( hihly
characteristic refractile syncytium formation of
of multinucleated iant cells (.@" effect in cell
culture)
o viral antien demonstration (=: on
nasopharyneal aspirates)
o seroloy( 1 serotype- .:;, N;
o rise in antibody titer of at least 2!
o tissue culture (mon%ey %idney
cells)( .@" by type +- uinea pi
<#. hemadsorption
o antienic detection (=: of infected
respiratory epithelial cells)
o seroloy( detect( early antibodies
to * (soluble) antien
InucleocapsidJ, late antibodies to
$(viral) antien Ihemalutinin
and neuraminidaseJ
o .:;, )=, N; (but seroloy
enerally of limited value)
/anaement o differential dianoses
o symptomatic treatment
o reconi6e and treat complications
o minimi6e spread by respiratory route
o A/AN;AD=N" active aainst influen6a A (but ineffective aainst )FN1 as
they3re resistant as farmers in .hina e!posed )FN1 to amantadine)
o Neuraminidase inhibitors (oseltamivir( ;amiflu that3s ta%en orally, 6anamivir(
<elen6a that3s ta%en as an inhalant) inhibit release of virus fro infected cells(
effective aainst influen6a A and #
o the above drus can prevent influen6a and useful in old people who haven3t been
immuni6ed but may have been e!posed- but vaccine3s still the most reliable
o ribavirin aerosol therapy may be beneficial
o ventilatory support
o isolate hospitali6ed children who3re infected
o passive immuni6ation with monoclonal antibody
directed aainst the fusion protein of <*$ (for
prophyla!is in premature'immunocompromised
infants)
o no antiviral therapy' vaccine
o ventilatory support
o antibiotics for secondary bacterial
infection
o sedation and hydration
o inactivated vaccine prophyla!is for hih ris% roups durin winter
o problems of vaccine( timely preparation a problem ' short-lived immunity,
incomplete protection' rarely, can cause >uillain #arre syndrome
o no effective vaccine o no vaccine in routine use
Adenovirus *hinovirus )oronavirus
o ?inear dsDNA, icosahedral capsid, no envelope
o pro8ectin fibers from each of the 1+ vertices of the capsid
(fibers are hemalutinins that mediate attachment)
o species-specific infections of many animals
o certain human strains cause malinant tumors (sarcomas 5 site
of in8ection) in baby hamster but not in humans
o N20 serotypes (most can hemalutinate)
o infects mucosa and lymphoid tissue
o can cause acute infections (death of cells) or latent infections
(espA in adenoidal and tonsillar tissues of the throat( adenoids
@icornavirus(
o animal viruses
o small (+0-70nm), na%ed icosahedral symmetry (no
envelope), ss<NA(L)
o + types( rhinoviruses and enteroviruses
o 4nteroviruses (hepAA, polio, co!sac%ie, echo)replicate
optimally at 71de, infect enteric tract, stable under
acidic p) (7-F)

o helical enveloped ss<NA(L), 100nm
o no virion polymerase
o at least 7 antienic types with some cross
reactivity
18
near pharyneal tissues)
;ransmissio
n
o aerosol droplets
o fecal-oral route (most common in children and their families)
o direct inoculation of con8unctiva by finers
o close contact
o respiratory droplets (personperson, deposition onto
hands' surfaces then transported to nose'eyes via
finers) Dpredominates in rainy season
o respiratory aerosol
=ncubation
period
o +-2days
.linical
features
Dwide variety of upper and lower respiratory tract diseases
o pharyno-con8unctival fever (sometimes epidemic, usually type
7, swimmin pool that3s not properly fluoridated)
o C<;= with fever (pharynitis)
o (atypical) pneumonia (?<;=)
o acute follicular con8unctivitis
o epidemic %eratocon8unctivitis (shipyard eye)
o inflammation of cornea and con8unctiva
o iatroenic disease preventable by strict sepsis
and handwashin
o types 8K1M
o hemorrhaic cystitis
o common in paediatric oncoloy patients due to
damae to bladder interstitial epithelium and
blood vessels by the virus'to!ins
o hematuria, dysuria
o due to "A coli, papovirus, influen6a A too
(bladder inflammation)
o types 11K+1
o astroenteritis (inflammation of stomach K intestines, affects
mesenteric lymph nodes at lower riht &uadrant, presents as
appendicitis with abdominal pain), mesenteric adenitis (&uite
common), intussusception
o astroenteritis with nonbloody diarrhea usually
in children E+yrs of ae
o chronic infection of tonsils and adenoids
o adenovirus infections endemic -orld-ide! outbreaks common
among military recruits (types 8393:3;) respiratory disease)
o most adenovirus infections resolve spontaneously (almost T are
asymptomatic)
*hinoviruses replicate optimally at 77de (infects nose'
con8unctiva more often than ?<;), is acid-labile (thus
infections limited to nose and throat)
o N100 serotypes (many re-infections)
o may undero enetic'antienic variation
o inhabits upper respA tract
o host rane limited to humans K chimpan6ees
o hih incidence in childhood
o common cold (also caused by adenoviruses, influen6a .,
co!sac%ievirus)
o entry 5 C<; and remains locali6ed there since they
row poorly at 71de
o rhinorrhea, snee6in, sore throat, couh, mild fever,
hoarseness, headache (chilly sensation but there3s few
other systemic symptoms)
o lasts 1-+wee%s
o complications (rare)(
o sinusitis
o otitis media
o pneumonia
o may precipitate asthmatic attac%s and
aravate chronic bronchitis
#eta-pneumovirus
o discovered in +001
o infants and children with acute respA disease (severe
o +nd only to rhinoviruses in causin common
cold (causes 1FB of total) Gcommon cold 9
cory6a, rhinorrhea, scratchy sore throat, low
rade fever
o mucosal infections in domestic animals
o occurs worldwide, early in life (Abs in half the
children)- outbrea%s usually in winter
o F0B of infections are asymptomatic
o diseases usually last for several days with no
lon-term se&uelae
$A*$: severe acute respiratory syndrome
o *A<*-coronavirus (.o$-*A<*)( the source
miht be from the many animal coronaviruses
as its enome se&uence is diffA from e!istin
human strains- but enome se&uence of diffA
isolates of .o$-*A<* very similar
(antienicity of *A<* is &uite stable)
o fever at least 78de, non-productive couh,
dyspnea, hypo!ia, chills'
riors'malaise'headache, sore throat and
rhinorrhea are uncommon- .U< reveals
interstitial roundlass infiltrates that don3t
cavitate- leu%openia, thrombocytopenia-
incubation peiod +-10days
o *A<* atypical pneumonia( diffuse edema
resultin in hypo!ia- bindin of virus to A."-
+ on surface of respA tract epithelium
contributes to dysreulated fluid balance
edema in alveolar space
o epidemioloy( from .hina (Nov 0+), N8700
cases, N18F deaths, 1FB case fatality rate
1M
bronchiolitis and pneumonia)
o most children infected by Fyrs
o asthma in children G acute whee6in attac%s
o symptoms similar to <*$ infections
o spreads &uic%ly in hospital settins,
humanhuman, some are super-spreaders
o manaement by &uarantine, respA infection
control procedures
o no specific treatment
o dianosis( antibody-based and @.<
<eplication
cycle
attach to cell surface via its fiber virus penetrates and uncoats
viral DNA moves to nucleus host cell3s DNA-dependent <NA
polymerase transcribes early enes, splices introns functional
m<NA produced early m<NA transcribed into nonstructural
proteins in the cytoplasm viral DNA replication occurs in nucleus
late m<NA transcribed and translated into structural virion
proteins viral assembly in nucleus virus released by lysis of cell
bind to cell surface receptor =.A/-1 which is found on many
cell types enters cell uncoatin (capsid proteins
removed) enome <NA functions as m<NA and translated
into a lare polypeptide polypeptide cleaved into many
proteins (a <NA polymerase that ma%es proeny <NA
enomes) assembly of proeny virions virions
accumulate in cell cytoplasm and released upon death of cell
(no buddin)
$irus adsorbs to surface with hemalutinin spi%es
enters cytoplasm where it3s uncoiled L<NA
translated to polypeptides (some form <NA
polymerase that replicates the enome) m<NAs
synthesi6ed and translated into structural proteins
virus assembled and obtains envelope from "<
=mmunity o immunity based on the neutrali6in antibody is type-specific
and lifelon
o neutrali6in antibody protective aainst the same
serotype (serotype-specific immunity by nasal secretory
=A)
o immunity is brief- can have re-infections
Dianosis o tissue culture (human embryonic or )e?a cells)( swellin and
clusterin of infected cells with intranuclear inclusions (bunch
of rapes)
o seroloy( =: for rapid detection of viral antien in
nasopharyneal aspirates- .:;')= to adenovirus common roup
antien- serotypin by N; (detect 2!'more rise in antibody titer)
o only for epidemioloical purposes
o isolation of virus form nasal secretions in cell culture but
it3s rarely done( tissue culture unstable below p)0,
optimal rowth at 77de, .@" in human embryo lun ()
rhinovirus) and mon%ey %idney cells (/ rhinovirus)
o usually by seroloy (N; for serotypin)
o electron microscopy( crown-li%e pro8ections
on virion surface (corona)
o hemalutinates <#.s
.ontrol vaccine aainst certain serotypes for military recruits Iadenovirus
infections endemic -orld-ide! outbreaks common among military
recruits (types 8393:3;) respiratory disease)#
o vaccine infects the >=;, causin asymptomatic infection and
inducin immunity to respA diseases
o monovalent vaccines that3re administered separately as they3ll
interfere with one another
o no specific antiviral therapy
o symptomatic treatment
o no vaccine due to lare noA of serotypes
o prevention( use paper tissues with citric acid which inactivates
rhinoviruses and sodium lauryl sulfate which inactivates
influen6a and <*$) to limit transmission when used to remove
viruses from finers contaminated with respiratory secretions
o tissue culture( difficult to culture- isolated in
human embryo trachea cultures with .@"
o no specific treatment' vaccine
4nteroviruses
o @icornaviruses
o small (+8nm) icosahedral ss<NA(L), with no envelope [sidenote4 (1& genome isnt infectious though its a ss<NA(=) as it needs reverse
transcriptase#
o 2 ma8or polypeptides on capsid
o stable
o insensitive to deterents (eAA 10B alcohol, dilute ?ysol, lipid solvents), but handwashin has a dilutin effect
o can survive for months at 2de, can survive e!posure to 00de
+0
o replicate in the >=;
o prefer warm moist environments (tropics, epidemic in summer months)
o classification(
o F different species (human enteroviruses A-D and polioviruses)
o newly discovered viruses( enterovirus UU (eAA enterovirus 11)
enterovirus 10( acute hemorrhaic con8unctivitis
enterovirus 11( encephalitis' hand-foot-mouth disease
recent outbrea%s in /alaysia (1MM1), ;aiwan (1MM8) miht be an important pathoen
enterovirus 1+( now called hepatitis A virus
o N00 different serotypes
4nterovirus .oliovirus )osackieviruses and 4chovirus )osackie%4nteroviruses: H5#6
o virus first rown in cell culture in 1M2M( the basis for
vaccines
o 7 serotypes
o lobal distribution (as of +002, there3re now reions that
are endemic'have re-established transmission'are
importation countries'are polio-free)
o .o!sac%ieviruses A and # divided
based on the histopatholoical
chanes they produce in newborn
mice and their capacity to row in
cell cultures
o "choviruses(
o 9 enteric cytopathic
human orphan
o produces cytophatic
chanes in cell culture,
non-pathoenic for
newborn mice and
subhuman primates
o 70 serotypes
"$11
o first described in 1M12
o common infection
o infection manifests as childhood e!anthema, the
):/D it causes is indistinuishable from .A10
o small proportion of infection results in .N* infection
o seroprevalence of "$11 in *inapore( antibody level
rises from ae+-F (most infections in preschool)- in
1MM8, 2FB of mothers had antibodies aainst "$11-
the maternal antibody level in the child declines within
1month and increases from +yrs onwards
o hihest seroconversion rate in children +-Fyrs
o seroconversion rate slows NFyrs
o neutrali6in Ab titer reduces with ae( indicates low
re-infection rate
o control of "$11 by controllin the pre-school
environment
;ransmission o o o
=ncubation
period
o 1-12days o o
.linical
features
o subclinical infection (78-79:!: vast ma8ority of
poliovirus infections (a successful pathogen that
replicates in host -ithout killing it)
o abortive infection (/-;:!( a minor influen6a illness with
)osackie A: epithelial infections
o herpanina (ulcers 5 soft
palate), hand-foot-mouth
disease (.A10), con8unctivitis
o
+1
recovery within a few days- may be accompanied by
aseptic meninitis
o ma&or illness (1-2:!: may present +-7days followin the
minor illness, or without precedin minor illness- sins of
aseptic meninitis common- involvement of anterior horn
cells lead to flaccid paralysis (due to polio in childhood 0
no muscle tone3 bones dont gro- one leg shorter than
the other)- involvement of medulla leads to respiratory
paralysis and death (bulbar poliomyelitis) G treated by
iron lung(-ith negative pressure)
)osackie B: muscular infections
o #ornholm3s disease (infection
of intercostal muscles that3s
sometimes mista%en for
appendicitis), myocarditis
Dboth types can cause encephalitis
"choviruses( wide rane of disease
spectrum
@athoenesis =nestion virus multiples in oropharyneal and intestinal
mucosa invasion of lymphatic system espA the tonsils and
@eyer3s patches of the ileum virus enters blood (transient
viraemia) virus may involve the .N* followin
dissemination in a minority of cases
=mmunity o disease became important with increased hyiene- almost
100B of children in developin countries infected before
ae F (children last time ot infected very early and developed
antibodies Iearly seroconversionJ increased hyiene 9 less
infections and less antibodies in children)
o o
Dianosis o o more useful for surveillance
only as the virus ta%es days-
wee%s to row
o .o!sac%ie # and echoviruses
can be readily rown in cell
culture from throat swabs,
feces, rectal swabs and .*:
o some .o!sac%ie A viruses can3t
be easily isolated in cell culture
o seroloy( rarely used due to
cross-reactivity Guseful for
epidemioloical studies
o molecular methods( <;-@.<,
enetic se&uencin
o
/anaement'
prevention'
o immuni6ation and poliovirus eradication campain has
eradicated poliovirus in most reions of the world
o no specific vaccine
o some use =$=> to treat neonatal
):/D
o common mild childhood infection
++
.ontrol @reventive $accination(
"ntramuscular .oliovirus Vaccine (".V!
o by Honas *al%
o consists of formalin-inactivated virus of all 7 serotypes
o =/, re&uires trained personnel
o confers immunity but recipient of vaccine still acts as a
carrier (=A not developed thouh => develops G the
vaccinated person won3t develop infection but the virus
still develops in the ut and can infect others)
o no ris% of vaccine-associated paralysis I$A@J
o vaccinates patients only
-ral .oliovirus Vaccine (-.V!
o oral, no medical trainin re&uired for administration
o lifelon immunity and prevents carriae (as the
vaccinated person develops =A too)
o small ris% of vaccine-associated paralysis I$A@J (the
mother' careiver must be vaccinated aainst polio too)
o secondary vaccination possible (the child3s vaccine can
serve as a booster for the mum'careiver as S@$ oes
into the stools)
o problems( $A@, reversion to wild type( thus the ris%s are
sinificant now that polio has been eradicated (risks cant
be >ustified -hen theres no polio around anymore thus
children not routinely vaccinated anymore)
polio has reservoir in contaminated -ater
infections' severe infections in
immunocompromised
individuals but efficacy
uncertain
o pleconaril is active aainst
certain enteroviruses
o caused by several different types of enteroviruses and
.o!sac%ie .A10, +2, and more recently "$11
o outbrea%s in *arawa%, @eninsula /alaysia, ;aiwan in
1MM1'1MM8
o thousands affected with hih mortality rate
o immunocompetent people affected too
o fever, oral ulcers, constipation, headache, vomitin,
vesicular lesions on hands'feet' oral mucosa or
herpanina, but usually not life-threatenin
o aseptic meninitis, myocarditis present too
o all the cases have rash (macules'papules' petechiae)
o deaths due to encephalitis and neuroenic pulmonary
edema (infection of brainstem cardiac failure
pulmonary edema)
o made a leally notifiable disease in Sct +001,
administratively notifiable since Apr 1MM8
o ):/D outbrea%s never due to only 1 serotype- 1
serotype may form the ma8ority but there3re always
other serotypes involved too
o outbrea% of ):/D in *inapore, *ep-Sct +000
o sudden deaths (2 deaths in a month) of youn
children (usually E+AFyrs)
o duration of illness usually +-Fdays
o increased virulence and tropism of some enoroups
of viruses, coinfection with a +nd virus (adenovirus L
enterovirus or .A10 L "$11)
o viral diseases tend to et more severe with increasin ae
o natural host doesn3t et %illed by pathoen (eAA humans die from influen6a A as humans aren3t the human host)
o nephrotic syndrome 9 edema due to %idneys lea%in protein treat with steroids, cyclosporine
o !imab 9 chimeric Ab, mumab 9 humani6ed Ab
.arvovirus < B17 virus .ovirus *abies
o simplest DNA virus, linear ssDNA
without envelope, icosahedral
o lare linear dsDNA virus, with double
membrane and lipoprotein envelope, comple!
o ?yssavirus of the <habdovirus family- linear ss<NA(-),
helical capsid with envelope- 170-+20mm
+7
capsid, ++nm
o 1 serotype
o worldwide (most people have
antibodies to #1M)
o
capsid symmetry, +F0-700nm
o contains DNA-dependent <NA polymerase
(replication in cytoplasm)
o %nown for centuries (.hina':ar "ast N+000 yrs
ao)
o have specific animal hosts
o contains <NA-dependent <NA polymerase
o characteristic bullet-shaped appearance with 0-1mm spi%e
pro8ections
o sinle antienic type( antienicity based on the envelope
lycoprotein spi%es
;ransmission o mainly via respiratory route
o throuh body fluids, blood
o vertical( motherfetus
(transplacentally)
o smallpo!( rapid spread via respiratory route of
transmission from lesions in the respiratory tract
(respiratory aerosol, direct contact with virus on
s%in lesions'formites)
o /.$( direct contact'fomites (towels, swimmin
pools) ' s%ins%in transmission after se!ual
intercourse
o rabies has broad host rane (infects all mammals) but only
some mammals are impt sources of infection for humans
o bite'inhaled in bat-infested caves (aerosols of bat secretions
containin rabies)- rare( coenea transplants from patients
who died of undianosed rabies
=ncubation time o 2days G +w%s o 1+days (for smallpo!), 1w%-0mths (for /.$) o +-10w%s or loner (dependent on location of bite( head
9shorter)
.linical
features
o common infection in childhood,
mostly asymptomatic
4rythema infectiosum (Fth disease)
o the other 2 macular'maculopapular
rash diseases of childhood( measles,
rubella, scarlet fever, roseola
o 1st phase( viraemic phase (virus
present in C<;, the site of sheddin-
symptoms appear at end of 1st w%(
fever'malaise'myalia'chills
'itchin, cory6a, sore throat
o +nd phase( mediated by immune
comple!es I=/, => with virus, can
lead to arthritis with rash espA in
womenJ( rash in 1'7 of patients 5
chee%( slapped chee% appearance
(briht red rash that3s prominent on
chee%s)- rash can loo% li%e lace on
trun% too( lacy, less intense
erythematous rash on the body
@o!virus-induced diseases (humans the primary host for
all 7)
Variola < smallpo (*A$H!
o now eradicated throuh Q)S international
cooperationG last naturally occurrin outbrea% in
*omalia in 1M11
o durin incubation, virus is distributed to internal
orans
o after incubation sudden onset of prodrome
(fever, malaise) sudden appearance of rash
(worse on face and e!tremities than then trun%)(
papular, vesicular'pustular (contains fluid'pus),
leavin pin% scars Iproression of rash( macular
papules vesicles pustules crusts (in +-
7wee%s)J
o severe infection with +0-F0B mortality
Vaccinia (causes co=po! < smallpo vaccination
(live attenuated vaccinia virus)
o variolation 9 administration of material from
%nown smallpo! cases to protect recipients
o Henner used cowpo! from a mil%maid to vaccinate
8yrold Hames @hipp Henner then challened
<abies 9 acute .N* infection that3s invariably fatal- ac&uired
throuh bite of a rabid animal (usually do) that manifests
aressive bitin behavior induced by viral encephalitis
<abies virus replicates in the striated' connective tissue 5 the
site of inoculation (bite site) enters peripheral nerves throuh
neuromuscular 8unction (infection of sensory neurons) spread
to .N* throuh the endoneurium of *chwann cells (a!onal
transport to .N*) there is widespread .N* involvement in
terminal disease virus multiplies in the $N? and travels do-n
peripheral nerves to salivary glands and other organs enter
saliva to be transmitted by bite
Ddurin transport within nerves, the virus is sheltered from the
immune system- little if any immune response- no viremic stae
=nfectivity of rabies virus determined by site and mode of
transmission
o site( nearer to brain 9 worse
.rodrome phase (1-2days!
o pain and paresthesia in area of bite, >= and upper respA
+2
o arthritis at small 8oints of
hands and feet bilaterally,
resemblin rheumatoid
arthritis
o hepatitis # and rubella also
immune-comple!-related
=n patients =ith chronic hemolytic
anemia (eAA sic%le cell disease,
thalassemia), #1M can cause transient
aplastic crisis (continuous lysin of
<#.s)
=n immunocompromised patients ()=$,
chemotherapy, transplant), #1M can
cause severe aplastic anemia
(leu%openia, thrombocytopenia- chronic
anemia due to chronic #1M infection)
=n pregnant patients (1stN+nd
trimester), #1M may cross placenta can
cause severe anemia in fetus (non-
immune hydrops fetalis in +nd
trimester)- fetal death in 1st trimester- no
sinificant clinical findin in 7rd
trimester [/)@ generally doesnt cause
significant congenital abnormalities as
the fetus dies -hen infected#
o death of #1M-infected-erythroblasts
in fetus severe anemia
conestive heart failure
hydrops fetalis (massive edema)
Hames with variola virus and showed that he was
protected
o $accinia virus for vaccination is prepared from
vesicular lesions produced in the s%in of calves and
sheep, or it can be rown in chic% embryos
o $accinia vaccination has certain ris%s ranin from
mild reactions to fatal encephalitis, vaccinia
gangrenosa (severe" fatal form of vaccinia in
immuno*compromised people -ith progressive
enlargement of the initial lesion)- incidence of
complications 1'800- severe complications
1F'million
o vaccinia could be a vector for immuni6ation
aainst other viruses'to protect aainst smallpo!
bioterrorism (due to complications3 routine
vaccination of civilians discontinued! for military
personnel)
o measures against bioterrorism4 vaccinate )st
responders so they can give emergency medical
care -ithout fear of contracting the disease! ring
immunization of unimmunized general population
(an e+posed individual can be immunized -ithin
9days)
o vaccinia immune globulins (&12) -ith high*titer
antibodies can treat most of the vaccinated*related
complications
#olluscum contagiosum virus (#)V! < many benign
skin nodules
o part of po!virus family but different from variola and
vaccinia
o small papule rows into discrete wa!y smooth dome-
shaped pearly'flesh-colored nodule (volcano
appearance with white crater in the center where virus
emeres)
o there3s usually 1-+0 lesions, sometimes 100s
o 5 trun%'pro!imal e!tremities for children-
trun%'pubic areas'thihs for adults
o individual lesions persist for + months- disease lasts
0mths
symptoms
o irritability, apprehension, sense of impendin death
o hydrophobia (due to painful spasm of throat muscles on
swallowin( aversion to water as swallowin is too painful)
o non-specific symptoms( fever, anore!ia, confusion,
lethary, increased salivation
o tinlin'itchin'burnin of s%in associated with peripheral
nerve damae
4citation phase
o hyperventilation, hyperactivity, disorientation, sei6ures
.aralytic phase
o lethary, early paralysis espA in areas innervated by the
cranial nerves and in somatic muscles'bladder'bowels
o radual involvement of cardiac muscles L paralysis of respA
muscles lead to death
Dencephalitis within .N* (death of neurons, demyelination)
4pidemiology(
o rabies virus prevalent in wildlife
o domestic do is the ma8or source in urban areas where
there3re no immuni6ation prorams for animals
o Qildlife may be responsible for human infection elsewhere(
"urope (fo!es, bats), /iddle "ast (wolves, dos), Asia
(dos), Africa (dos, monoose, antelopes), NA America
(fo!es, s%un%s, raccoons, insectivorous bats), *A America
(dos, vampire bats) Drodents and rabbits don3t transmit
rabies
+F
o tends to occur in children'those with reduced cellular
immunity- lesions in immuno-competent people are
self-limited but may last many months
o infection is usually benin and painless
o spontaneous recovery (treatment for cosmetic
reasons)
@athoenesis <eplicates autonomously in rapidly
dividin cells
o <#. precursors Ierythroblasts in
bone marrowJ which are in * phase,
but not mature <#.s)- as #1M
tarets human erythroid proenitor
cells in bone marrow, they can cause
lysis of cells leadin to anemia- and
can also affect
lymphocytes'ranulocytes' platelet(
aplastic crisis
o endothelial cells in blood vessels
(leadin to rash)
=nfects upper respA tract K local lymph nodes
enters blood (primary viremia) internal organs
affected virus re-enters blood (secondary viremia)
spread to s%in (rash due to viral replication in s%in,
and damae caused by cytoto!ic ; cells attac%in the
virus-infected cells)
*abies virus binds to Ach receptor on cell surface entry into
cell virion <NA polymerase synthesi6es m<NAs that code
for viral proteins and replicates the viral enome proeny
<NA assembled with virion proteins to form the nucleocapsid
envelope ac&uired as the virion buds throuh the cell
membrane
,ooneses
o diseases of vertebrate animals transmittable to man directly'
indirectly throuh an insect vector
o when an insect vector is involved, the disease is %nown as
an arthropod-borne(arboviral) disease
=mmunity o => persists and may offer lon-
term protection
o infected person recovers with lifelon immunity o ?ittle infoA %nown as very few ppl have survived rabies
Dianosis o #1M difficult to row
o use *"<S?S>V
o =/ appears after 2-
1days
o => appears 1-10days
later, persistin for
years (possible lon-
term protection)
o in immunocompromised patients,
antibodies may not be detectable-
detect viral DNA in blood by @.<
o prenancy(
o mother( seroloy( =/
and => (risin titers)
o @.< can detect #1M
*mallpo!
o easily rown in lab (row in cell culture)
o antienically comple!( induces both specific and
cross-reactin antibodies
o detect viral antiens in vesicular fluid by =:
/.$
o clinical appearance (s%in nodules with crater and
dome)
o confirmed by "/ (semi-solid caseous material
from lesions)
/.$ treatment'manaement(
o no vaccine
o remove lesions by curettae'li&uid nitroen
o histopatholoy G usin corneal scrapins' brain autopsy
specimens- N"><= #SD="* (infected neurons contin an
eosinophilic cytoplasmic inclusion called the Neri body)
are pathonomonic on histoloy (10B of cases) G important
dianostic feature
o rapid virus AN;=>"N D";".;=SN( widely used- corneal
impressions'nec% s%in biopsy- direct fluorescent antibody
test (D:A) commonly used
o the most definitive dianosis 9 $=<C* .C?;=$A;=SN
from saliva'infected tissue'.*: (cell cultures may be used
or more commonly, the specimen is inoculated
intracerebrally into infant mice)- rarely offered by
dianostic labs
o *"<S?S>V( circulatin antibodies appear slowly in the
course of infection but are usually present by the time of
onset of clinical symptoms (rise in titer)
+0
DNA in maternal
serum (or amniotic
fluid)
o ultrasound of fetus for
non-immune hydrops
o percutaneous umbilical
blood samplin
(@C#*) - invasive
o no specific antiviral therapy but cidofovir could
treat e!tensive lesions in the
immunocompromised
@re-e!posure immuni6ation for hih-ris% roups (vets'
6oo%eepers'travelers to endemic areas)
o 7doses on 0'1'+1or+8
o booster doses needed to maintain antibody titer of 1(F
;reatment
/anaement'
prevention'
.ontrol
o no %nown specific treatment (not
needed in most cases) G pooled
immune lobulins may be beneficial
for chronic #1M infection in patients
with immuno-deficiency
o blood transfusion for transient
aplastic crisis
o fetal infection( watchin waitin
(conservative manaement), hih
dose => therapy, intrauterine fetal
transfusion for serious cases
o vaccine or chemoprophyla!is
unavailable yet
o avoid e!posure durin prenancy
*uccessful eradication of smallpo! due to(
o no other reservoir for the virus besides man
(includin primates) G arboviruses have
reservoirs besides man- polio has reservoir in
contaminated -ater
o variola virus only causes acute infections and
the infected person either dies or recovers with
lifelon immunity (herpes not like that)
o vaccinia virus is an effective immunoen
o sinle, stable serotype without varied
antienicity li%e influen6a
o antibody response is prompt (e!posed person
can be protected if vaccinated within 2days)
o disease is easily reconi6ed clinically (e!posed
persons can be promptly immuni6ed)
*abies Vaccines
o inactivated whole virus vaccines for humans( )uman diploid
cell vaccine ()D.$) Iinactivated virus rown in human
diploid cellsJG the best vaccine available now with nearly
100B efficacy and rarely any severe reactions- iven =/'*.
into deltoid area of upper arm, in F doses at days 0'7'1'12'70
o inactivated vaccine for dos
o live attenuated virus vaccines underoin trials for wild
animals
.ost-eposure .rophylais (rabies vaccine routinely used post-
e!posure as the incubation period is lon enouh to allow virus in
the vaccine to sufficiently induce protective immunity)
o factors affectin decision to ive post-e!posure prophyla!is(
type of animal (iven to all wild animal attac%s), whether the
domestic animal was immuni6ed ade&uately (K whether the
attac% was provo%ed), whether rabies is endemic in that area
o wound treatment (to viral load at bite site)( bites'scratches
thorouhly washed with soap and water (incidence of rabies in
animals can be reduced by local treatment alone,
e!perimentally)
o passive immuni6ation (iven once with first dose of )D.$)(
human rabies immunolobulin (from hyper-immuni6ed
persons) ma! dose iven around the area of the wound, and
supplemented with an =/ dose to confer short-term protection
o active immuni6ation ()D.$) used at different site from
wound
)ontrol of *abies
o urban( canine rabies accounts for MMB of human rabies G control
by stray do control, do vaccination, &uarantine of imported
animals
+1
o wildlife( onoin trials in "urope where bait with rabies vaccine is
iven to fo!es (success in *wit6erland)
$lo= Virus 6iseases $ubacute spongioform encephalopathies
o viruses causin proressive patholoical processes
involvin mainly the .N*
o radual onset, proressive invariably fatal course
o have clinically silent lon incubation periods of
many months'years
o no antimicrobial therapy
o replicate rate of these viruses similar to other viruses
o neuroloical diseases due to unconventional aents (prions)
o sponioform ' vacuolatin deeneration in the brain
$ubacute sclerosing pancephalitis ($$.4! <
#easles
o slowly proressive- persistent infection
by a variant of measles that can3t
complete its replication (but has
disappeared with measles vaccine)
o inflammatory lesions in many areas of the
brain
o beins with mild chanes in personality,
endin with dementia K death
$$.4 (congenital infection! < *ubella
o proressive panencephalitis in patients
with conenital rubella
.rogressive #ultifocal
>eucoencephalopathy ?.#>@< A) (human
polyomavirus!
o fatal demyelinatin disease of white
matter affectin multiple areas of the
brain
o only in immunocompromised patients
(leu%emia, lymphoma, those receivin
immunosuppressants, chemotherapy)-
increasin importance now due to A=D*
.rions
o the causative agent of transmissible spongiform encephalopathies of humans and animals
o not conventional viruses (incorrectly termed as slow viruses)
o contain SN?V proteinaceous material, devoid of nucleic acidsIno <NA'DNAJ (@roteinaceous =nfectious @articles)
o small si6e (E70nm)
o hih resistance to chemical'physical aents eAA heat'formaldehyde'C$ liht' nucleases that usually wor% aainst viruses (resistant
to temps usually used in cooking! thus transmission by food possible e.g. in $AD) 0 inactivated by protein"lipid*disrupting agents
(e.g. phenol3 ether3 NaB(3 hypochlorite) and autoclaving
o prions can be ac6uired by ingestion survive digestion in 21' penetrates gut mucosa amplified -ithin follicle dendritic cells
in lymphatic tissue e.g. Ceyers patches prions carried by migrating dendritic cells to spleen spread to $N? from spleen via
sympathetic nerves
o not immunoenic (no response by body) G this is because prions are encoded by normal cellular genes (no inflammatory response
in infected brain tissue 0 vacuolated spongiform appearance found -ithout inflammatory cells)
o not uniformly distributed in tissues (concentrated in brain tissues)
o normal prion protein CrCc [prion cellular protein# has significant alpha*helical conformation (non*pathogenic) but -hen it
changes to beta*pleated sheet CrCsc [prion protein scrapies#3 these abnormal forms aggregate into filaments -hich disrupt
neuronal function and cause cell death
o abnormal prions combine with normal cellular protein to induce replication of the abnormal form (prions Oreproduce3 by the
abnormal beta-pleated sheet form recruitin normal heli! forms to chane their conformation- beta and helical forms have same aa
se&uence but 8ust conformational difference- recruitment is an essential step to noA of abnormal pathoenic particles)
#an:
'uru (transmissibleB caused by infesting"handling brain tissue!
)reut,feld-Aacob ()A6!B ?sporadic% 18: inherited@
o human form of mad cow disease ac&uired when humans eat the meat of infected cows
+8
I10B of patients with @/? have )=$
infectionJ
o H. virus( circular, dsDNA- present in
many people Iantibodies to H. found in
1FB of normal people and the virus
persists 5 %idney and e!creted in urineJ
but only causes problems in the
immunocompromised
o H.$ infects oliodendrocytes
and %ills them G causes syncytia
in astrocytes
o reactivation of latent H.$
infecetion in
immunocompromised patients -
dissemination via blood
o doesn3t appear to be contaious- primary
infection probably occurs in childhood
$ymptoms and $igns
o mental status chanes speech'lanuae
deficits, visual deficits enerali6ed or
focal wea%ness
o neuroloic sins( lac% of coordination,
cranial nerve palsies, loss of vision,
sensory loss, lanuae disturbances,
unsteadiness
o proressive to blindness, dementia, coma,
death within 0mths
6iagnosis
o definitive dianosis re&uires brain biopsy
o clinical dianosis by detectin focal
lesions and abnormalities of white matter
on neuroimain studies (.;'/<=)
o @.< of H.$ DNA from .*: used
recently
+o effective treatment
o the disease only ets worse
o worldwide distribution- familial clusterin in ?ibyan-Hews (hereditary cases could be due to mutations in erm cells)
o sporaic! no increased risk -ith dietary habits"occupation"animal e+posure
o ae of onset( 20-00
o male(female 9 1(1
o mode of transmission un%nown () blood transfusion case so far -here prions reached brain via lymphocytes! no evidence for
personperson or transplacental transmission)
o iatroenic transmission documented( corneal rafts, rowth hormone derived from human pituitary land, rafts of dura mater
from cadavers, contaminated electrodes for "">
o clinical features
o lon incubation period (yrs)
o dementia (-ith behavioral changes3 memory loss3 confusion), ata!ia, myoclonic 8er%s, death within 1yr
o patholoy( deeneration of .N* with vacuolated neurons (sponiform appearance), fibrous liosis (holes in brain) G
holes result from dead neurons and replacement by fibrous tissue (neuronal vacuolation and neuronal loss rather than
demyelination! spongy cheese*like holes in brain parenchyma)
o no virus particles seen in brain
o encephalopathy 7 pathological process in the brain -ithout signs of inflammation vs encephalitis 7 inflammatory
process in brain -here neutrophils and lymphocytes are present
o ""> shows periodic sharp wave comple!es
o no inflammatory reaction, no antibody or cell-mediated immune response elicited- prions found in the brains of .HD
patients (prion proteins in infected brain tissue form rod*shaped particles that are morphologically and histochemically
same as amyloid thats found in brain tissue in $N? diseases)
o immunosuppression has no effect on pathoenesis of disease
o dianosis by(
o detectin sponiform chanes in brain biopsy specimen G neuronal loss and liosis, amyloid pla&ues, florid pla&ues
o brain imain and electroencephaloram
o immunohistochemistry (labeled anti-prion antibodies stain the patient3s brain specimen)
o no treatment'drus for prevention
+e= Variant )A6 ?nv)A6@ (transmissible G possibly ac&uired by eatin meat'nervous tissue from animals with mad cow disease!
o in youn (vs old in .HD)
o proloned disease course (vs rapid in .HD)
o behavioral chanes (vs dementia in .HD)
o fre&uent @r@ pla&ues seen (vs infre&uently seen in .HD)
Gerstmann-$traussler syndrome (hereditary'enetic due to mutations in erm cells)
Animals:
+M
$crapie (sheep, goats!, scrapie in captive animals
Bovine spongioform encephalopathy: nv.HD differs clinically from other human **"s and nv.HD cases followed the sharp increase
in #*" cases in the late 1M80s (cross-species transmission via oral route in animals)- profiles of @r@sc from #*" and .HD
(electrophoretic mobility and lycosylation) are similar
70