DNA ENVELOPED VIRUSES

HERPES VIRUSES
Enveloped (ether sensitive), Regular Icosahedral capsid composed of 162 capsomeres, linear ds DNA (stale),
no polymerase, 100-180nm
Replicates in nucleus, !orm eosinophilic Intra Nuclear inclusions (e"cept E#$), only viruses tt obtain
envelopes by budding frm nuclear membrane
- early inclusion Cowdry type A inclusion body
%roduces characteristic giant cells
&atenc'( !ollo)ing primar' infection, herpes viruses se*uester into sites )here the' remain *uiescent+
Latent infections. Reactivation upon immonosuppressioninciting agent e!posurefeverstressmenses.
- symptoms as a result of reactivation may be similar or diff to original one
, neutralising As formed after 1- infection does not prevent reactivation ecause of location of
latent virus in immunoprivileged site
, - Note( Reactivation does not stimulate a rise in antiod' titre
"ubdivided into # families based on types of cells infected and sites of latency
- Alp$a-%&' %"&1, %"&(, %%&# )&*&+, %erpes ,)only affects mon-eys, if $umans are scratc$ed by
mon-eys, encep$alitis ensues+ epit$elial cell infection, latency in neurons
- ,eta-%&' %%&. )C/&+, %%&0 )%uman , Lymp$otropic &irus+ &ariety of tissues
- 1amma-%&' %%&2 )3,&+, %%&8 4nfection and latency in lymp$oid cells
- %%& 5 not medically impt
Association )ith cancers
, E#$ ( #ur.itt/s l'mphoma and N%0
, 11$2( 3aposi/s 4arcoma
#1 HERPES SIMPLEX VIRUS
%rimar' infection mostl' suclinical (ut in adults ma' e severe ) rash lasting 5,6 ).s)
$esicular eruption proliferation, allooning, degeneration, serous7clear fluid )ithin lesion
%roduces poc.s on chorio,allantoic memrane
8ransforms hamster cells
14$1 doesn/t form pla*ues in chic. emr'o la'ers+ 14$ 2 does+
Earl' inclusion 9 0o)dr' t'pe A inclusion od'
14$ 1 14$2
&ocation of
lesions
Aove )aist (2:;) #elo) )aist (2:;)
Diseases Acute <ingivostomatitis
, vesicles on uccal mucosa
, gums ulcerate ) gre' slough
, fever, l'mphadenopath'
, fetid breat$
, mainl' in children
, $eals spontaneously in (-#w-s
, most common primar' disease
, primary disease 6 severe t$an
recurrences
<enital herpes
, painful vesicles at genitals and anus
, vesiculoulcerative
, dysuria
, uret$ral or vagina disc$arge
, itc$
, more severe and protracted in 17 disease
, 17 infections fever and inguinal
adenopath', malaise
, asymptomatic infections are fre8uent
, many c$ildren $ave
asymptomatic primary disease
Recurrent 1erpes &aialis
(cold sores7fever listers)
, milder
, commenest recurrent form from
reactivation of 14$ in
trigeminal ganglion
, crops of vesicles, usu at
mucocutaneous =unction of lips
or nose, later ) painful ulcers
, recurrent infections fre8uently
at same sites
3eratocon=unctivitis
, lesions of con9 epi
, oedema and vesicles of e'elids,
, cornea( dendritic .eratitis,
ulcers, opacification, lindness
, recurrences can lead to
scarring and blindness
- Note( 0areful )ith steroid e'edrops>
Immunosupression )ill )orsen the
situation+ <ive anti viral instead>
Acute necroti?ing encephalitis
(0N4 inflammation)
, meningitis, perivascular
infiltration, neuronal
degeneration
, necrotic lesion in one temporal
loe
, sudden fever, headache,
confusion, vomiting, sei:ures,
altered mental states
, onset may be acute or
protracted
, disease is a result of 17
infection or recurrence
, high moridit' )ith
neurological deficits
, high mortalit'
, spinal tap reveals increased
l'mphoc'tes, proteins
, %0R 04! for confirmation
, #rain iops', viral isolation, I!
, Rare ut severe
1erpetic @hitlo)
, pustular lesion of s-in of finger
or $and of $ealt$care wor-er
, recurrent painful lesions from lumar and
sacral ganglia
Neonatal 1erpes
, originates c$iefly due to contact of lesions
at birt$ canal, sometimes due to
asymptomatic s$edding
, severe generali?ed infection ac*uired from
infected irth canal of mother (esp )ithout
protective maternal As)
, can be ac8uired t$roug$ $andling of baby
)%"&1 as well+
, s'mptoms var', as'mptomatic, mil- local
lesions, severe generali:ed diseases,
encep$alitis
, Aaundice, hepatosplenomegal',
thromoc'topenia, large cutaneous
vesicles
, ;espite t$eir association wit$ neonatal
infections, neit$er %"&-1 nor %"&-(
causes congenital abnormalities to any
significant degree
- Note( 8o prevent, Deliver ' caesarian section
Aseptic Beningitis
, usually mild, self-limited disease wit$ few
se8uelae
, ot$er complications are' transverse
myelitis )doesn<t go up all t$e way cause it
gets stuc- somew$ere+, sacral
radiculopat$y
Recurrent mucocutaneous 14$
, more locali:ed
, milder symptoms
, duration of episode s$orter
, prodromal signs
, tingling, s$ooting pains = to 28 $rs before
eruption
, %"&( detectable even wo bro-en lesions
prodrome only
- Note( %atients )ho has 14$ 2 has high ris. of
contracting 1I$, and 1I$ ris. )ill e
more serious
0ervical and $ulvar 0arcinoma
, 14$ 2 ma' e hit and run oncogenic virus
, 4tronger assoc ) human papillomaviruses,
esp t'pes 16 and 12
, 1igh fre*uenc' of 14$ 2 As in patients
cf matched ctrls
due to contact )ith oral
secretions of infected patients
, serous e"udates
- Note( cf staph'lococcal )hitlo) )
purulent e"udate
Disseminated infections, s+a+
, 1erpes hepatitis, 3sop$agitis,
>neumonia in patients )
depressed 8 cell function
Ec?ema
, Ec?ema 1erpeticum )dual
problem+, underlying s-in
disease ? %erpes added
, 3aposi/s $aricelliform eruption
, 4uperinfection of chronic
ec?ematous s.in ) e"tensive
vasiculation, fever
, 4ignificant mortalit'
Aseptic Beningitis
, Cccasional detection of 14$2 DNA,RNA
Ags in iopsies
Impt properties Borphologicall' indistinguishale+
Distinguish ' t'pe specific monoclonal antisera or ' %0R
Replicative
0'cle
(ait of conflict
t) notes n
&evinsons)
Attaches to cell surface at site of R for fibroblast 1@, fuses )ith cell mem
3ntry, uncoating, genome DNA enters nucleus, linear circular ;AA
mRNA transcried by $ost cell RAA polymerase
earl' structural (capsid) proteins formed
translation into early non structural proteins in cell cytoplasm s.a. t$ymidine -inase,
;AA polymerase target of drugs
3arly protein synt$esis immediate early, early, late )begins w$en viral ;AA polymerase
replicates its genome ;AA. Late proteins t$en transported into nucleus.
$iral DNA pac.aged into capsids
$iral gl'coproteins are incorporated into the nuclear memrane to form the viral envelope
$irions ud out through the nucleus and are released at the cell surface (cell l'sis)+
4n latently infected cells
- /ultiple copies of %"&-1 ;AA are found in cytoplasm of infected neurons
- Bnly a few genes are transcribed, and none are translated into protein
8ransmission
and
Epidemiolog'
1+ 4aliva (e+g+ .issing)
- Bral se!ual practices can reverse
convention.
2+ As'mptomatic shedding (esp in secretion)
5+ Direct contact )ith active lesions
6+ Autoinnoculation possile
20C $ave recurrent $erpes labialis
Infection most common in childhood and
often as'mptomatic+ Another pea. in
adolescence
1+ 4e"ual contact
, Bral se!ual practices can reverse
convention
2+ As'mptomatic shedding (esp in secretions)
5+ Direct contact )ith active lesions
6+ Autoinnoculation
No ma=or communal outrea.s No ma=or communal outrea.s
%athogenesis
and Immunit'
Replicate in t$e s-inmucous membrane )peribasal intermediate epit$elial cells+ at initial
site of infection
8hen migrates up the neuron and persists lifelong in a latent state in the sensor' ganglion
cells )trigeminal or lumbarsacral+
Inducers( sunlig$t, $ormonal c$anges )eg during menses+, trauma, stress, fever,
immunosuppression
Bigrates do)n neurons D replicates in s.in, causing lesions
- typically a vesicle containing serous fluid filled w virus particles n cell debris.
- 7 Aote' /ulti Aucleated 1iant Cells typically at base of lesions
4mmunity
- type specific, but some cross protection occurs
- $owever, immunity is incomplete D bot$ reinfection and reactivation can occur in
presence of circulating lg1
- cell mediated immunity impt in limiting %%&
Immunolog' Ne)orns have passive maternal As lasting 6 mths
14$ 1 infection ac*uired earl' in life E Almost 1::; have As ' adulthood
14$ 2 ac*uired usuall' after puert' E Aout 2:; se"uall' active adults have As
8reatment Ac'clovir(Ac'cloguanosine)
, converted ' 14$ specific
th'midine .inase to
monophosphate
, lo) to"icit'
, I$, topical, oral
, Encephalitis D s'stemic disease
due to 14$ 1 4& s$ortens
duration of lesions and reduces
e!tent of viral s$edding
, Dendritic ulcers, cold sores
topical
, %roph'la"is in
immunocompromised
, 4ome value for recurrent disease
@oscarnet
, for patients wit$ mutant %"& 1
resistant to acyclovir
Ac'clovir
, for primary and recurrent genital herpes
4& or oral or topical
, neonatal $erpes
$alac'clovir ($altre")
, &,valine ester of ac'clovir converted to
active metaolite, ac'clovir
, - Note( greater ioavailailit'
, suppresses recurrences of genital $erpes
$idaraine, 8rifluridine ($iroptic),
Ido"uridine
, for herpetic .eratitis
- Note( No drug treatment of the primar' infection can prevent recurrencesF drugs have no
effect on latent state, ut the' are proph'lactic, long term admin can suppress recurrences+
&a Diagnosis $irus isolation
, vesicle fluid, s.in s)a, saliva, tears, corneal scrapings, rain iops'
, inoculation of cell cultures 0%E of rounded cells in 62 to G2 hrs, N8 or I! )ith
specific antisera
, 4crapings Bultinucleated <iant cells (8?an. 0ell microscor')
, #H8 insufficient evidence to indicate viral aetiolog' since 14$ is found in
as'mptomatic su=ects
4erolog'
, N8, 0!8, E&I4A, RIA, I!
, %rimar' 14$ infection Neutralising 14$ IgB A
, 4ignificant rise in A titre 2,6 )ee.s after primar' infection
- Note( Recurrent infection 1igh levels of e"isting A, ut NC RI4E in titre
0ontrol Avoidance of infected sources and sites
Ac'clovir given earl' in primar' infection
$accines 9 e"perimental
, little value after primar' infection

- Note( , Impt to distinguish t) ulcers due to antiiotic allergies and 14$
, @hen ta.ing s)as, scrape #A4E of lesion
E $iruses are oligate I0 parasites> 8he fluid )on/t have much+ Need cells>
#2 VARICELLA ZOSTER VIRUS
- Note( &esions in chic.en po" E in $ARIIN< degrees of evolution
&esions in smallpo" E all in the 4ABE stage of infection
$aricella E primar' disease, ?oster E recurrent form
&*& similar morp$ologically and structurally under 3/ to ot$er $erpes viruses, ut Ag diff
4ingle serot'pe
1ighl' infectious
%umans D natural $osts
8ransmission 1+ Respirator' droplets (nose or mouth)
2+ Direct contact ()ith lesions frm varicella cases+ less commonl' from ?oster cases)
5+ 4aliva
%athogenesis 4nfects mucosa of ERF &iremia to s-in )vesicular ras$ occur+
Replicates in regional LA primary viraemia in R3 system
"econdary &iraemia &*& in cutaneous epit$elial cells
, pple are infective a few days before ras$
, @ever, $eadac$e 1-( days before t$e ras$ starts
Causing vesicular ras$
/ultinucleated giant cells w 4A inclusions seen at base of lesions
Latency in dorsal root ganglia
Later in life, suppression of C/4 or local trauma, virus is activated
&esicular s-in lesions, nerve plain
0linical
!indings7
Diseases
$aricella
, incuation 2,5).s
, ,rief prodromal syndromes of fever and malaise
, %apulovesicular rash appears 1
st
in crops on trun., then spreads to head and
e"tremities (centripetal distriution)
, Rash evolves from vesicles to pustules, then finall' crusts
, 4tc$ing )pruritis+ esp in vesicles
, Bore severe in adults, mild in .ids
, 0omplications(
(i) 4.in super infection (staph or strep)
(ii) Aseptic Beningitis
(iii) Neurological s'ndrome
(iv) %ost infectious encephalom'elitis (1 ). after rash) E Rare+
(v) %neumonia
, )ith 0ough, d'spnoea, h'po"ia, diffuse nodular infiltrate, pulm
calcification, ma' e fatal+ Rare
(vi) 1emorrhagic (!ulminating $aricella)
, leading to thromoc'topenia,DI$0
(vii) Arthritis
(viii) 0ongenital $aricella
, - rare transplacental infection in neonates orn to mothers )ith
varicella in earl' pregnanc'
(i") Neonatal varicella
, child contracted disease from mother near time of deliver' )hen there
is little7no protection from maternal As
, 1igh mortalit' in severe disease+
(") Cver)helming $aricella 9 in immunosuppressed patients
)!i+ Reye<s syndrome
- c$aracteri:ed by encep$alopat$y and liver degeneration
- associated wit$ &*& and influen:a ,
- pat$ogenesis un-nown.
- prevalance according to climate
- 4n temperate countries, c$ildren increased ris-
- 4n warm climates, adults increased ris-.
Joster
, clustered dermatomal vesicles, won<t cross midline of body
, recrudescent disease occurring in s.in dermatome of sensor' N ganglia
(cranial or dorsal)
, >ain can last for wee-s
, %ainful vesicular eruption morphologicall' similar to varicella+
, 4.in distriution corresponds to one or more sensor' root ganglia(
(i) 8horacic 9 K:; (#elt of roses)
(ii) 0ervical 9 2:D
(iii) &umar 9 2:;
(iv) 8rigeminal nerve 9 1K;
, Involvement of ophthalmic division ma' cause iridoc'clitis, .eratitis,
corneal ulceration
(v) <eniculate ganglion
, Ramsa',1unt,4'ndrome E $esicles in e"t+ auditor' canal, t'mpanic
memrane, anterior tongue, facial nerve
pals'
, 0omplications(
(i) %ost,?oster neulralgia (esp in elderl'+ 0an e deilitating)
)ii+ ;isseminated infections )e.g. pneumonia+
, in immunocompromised patients
, life- t$reatening
(iii) Encephalom'elitis
)iv+ Lymp$ocytic p$agocytosis in C"@
(v) Disseminated ?oster vesicles outside involved dermatomes in
immunosuppressed
- Note( Joster )ill not spread ?oster, ut ma' sometimes cause varicella spread
8reatment 4'mptomatic (for chic.enpo")
, antip'retics, antipruritics
, $JI< proph'la"is in e"posed high ris. immunocompromised
Ac'clovir
, in severe varicella pneumonia or harmorrhagic varicella
, in immunocompromised children )ith varicella
, immunocompetent patients wit$ &aricella treated wit$in (2$rs can reduce
fever, lesions. ,ut no impact on complications
, 0an limit progression of ?oster if given earl', even in immunocompromised
@oscarnet )alternative to acyclovir+
@amciclovir G &alacyclovir
- to decrease $ealing time in :oster
0ontrol for
$aricella
prevention
%h'sical arriers
$JI< proph'la"is for immunocompromised or pregnant )omen
&ive attenuated vaccine for high ris. patients
, avoid pregnant )omen or immunocompromised
&a
diagnosis of
$J$
$esicles
, stained smears of scrapings of s)as from ase reveals BN<0s
, I!
, EB to distinguish from po" viruses
, <el diffusion using specific antisera to detect 14$, $J$, $$ Ags
$irus Isolation
, In human firolast cultures !ocal 0%E, no free virus in medium
, I!, N8 of isolate )ith specific antisera
4erolog'
, 0!, N8, I!, E&I4A
, IgB found in oth recent varicella and ?oster
, Rise in A tire
, 1igh levels of neutrali?ing A in ?oster
#3 CYTOMEGALOVIRUS
"o named because giant cells are formed
EB morpholog' similar to t'pical herpes virus
Ale to transform human and hamster cells in culture
"ingle serotype
0linical
!indings7
Diseases
1+ 0ongenital 0B$ infection
, foetal infection and damage follo)ing maternal viraemia in an' trimester of
pregnanc'
, primar' maternal infection usuall' as'mptomatic
, usually in primary maternal infection, mom $as no Ab to fig$t off virus
before it infects infants
, ris- $ig$est in 1
st
trimester
, varied se*uelae mostl' mild, severe in at 2:;
2+ 0'tomegalic Inclusion Disease
, severe generali?ed 0B$ infection of infants
, intrauterine or perinatal infection
, Aaundice, hepatosplenomegal', interstitial pneumonitis, thromoc'topaenia,
hemol'tic anemia, 0N4 se*uelae (microcephal', periventricular
calcification, chorioretinitis, optic atroph', mental retardation, spasticit',
epileps')
, Affected organs sho) enlarged cells )ith large intranuclear Lo)l/s e'eM
inclusions
, Rare ut severe
5+ %ost Natal hepatitis
, hepatomegal'
, anormal &!8
, =aundice ma' e present
6+ Infectious Bononucleosis s'ndrome (Epstein,#arr li.e)
, spontaneous in other)ise health' 'oung adults
, post perfusion s'ndrome or after open heart surger'
, clinicall' similar to glandular fever ut less phar'ngitis and
l'mphadenopath'
, mild hepatitis
, circulating at'pical l'mphoc'tes (0B$ mononucleosis)
, #ut asence of heterophile As
, 0B$uria
, 0B$ isolation from peripheral lood l'mphoc'tes
K+ Infection in the immunocompromised host
, Eg+ c'toto"ic, radiotherap', cancer, organ transplantation, AID4
, primar' infection can also occur )ith organ transplant or lood transfusion
, recrudescence follo)ing reactivation of latent infection severit' from
mild to severe, depending on degree of immunosuppression
, 0B$ pneumonitis, hepatitis
, Disseminated 0B$ N fever, leucopaenia, pneumonitis, hepatitis, colitis,
rhinitis
, 4n A4;", C/& often attac-s
- 14F H intractable diarr$ea
- Retinitis H blindness
6+ <uillain,#arre 4'ndrome
8ransmission 1+ %lacenta, irth canal, reast mil.
2+ 4aliva (common in 'oung children)
5+ 4e" 9 present in semen and cervical secretions
6+ Hrine
K+ #lood transfusions
6+ Crgan transplants

- Note( E"cretion rate D A titres increased in immune deficienc' induced '
immunosuppressive agents, pregnanc', deilitating disease
Epidemiolog' OK:; adults have A against 0B$
usually asymptomatic in $ealt$y $osts
%athogenesis 0B$ enters a latent state in leu.oc'tes and can e reactivated )hen cell immunit'
is lo)ered
C/& infection causes an immunosuppressive effect by in$ibiting F cells, w$ic$
can lead to systemic disease
8reatment <anciclovir
, moderatel' effective in treatment of life threatening 0B$ retinitis, colitis, and
pneumonia in AID47immunocompromised patients
@oscarnet D also useful but causes more side effects
Cidofovir&alganciclovir D for retinitis
@omiversin D an antisense ;AA for intraocular treatment
- Note( 0B$ is ver' resistant to Ac'clovir
&a
Diagnosis
1+ $irus isolation
, from urine, throat s)a
, inoculate into human emr'o lung cultures
, slo) characteristic 0%E of foci of s)ollen cells
, Lo)l/s e'esM inclusions after 2,5).s
2+ $iral detection
, Des*uamated cells in urinar' sediment, Lo)l/s e'esM inclusions
, EB, viral antigen, DNA
5+ 4erolog'
, N8, 0!, RIA, I!, E&I4A (IgB and Ig<)
Immunolog' As in most humans e"cept 'oung children )ithout 0B$
0B$ secreted in urine even in asence of serum neutrali?ing A
0ontrol Isolation of ne)orns )ith severe 0B$ infections
4creening of organ and lood donors and recipients
0B$I< proph'la"is in 0B$,seronegative organ recipients receiving organs from
seropositive donors
&ive 0B$ vaccine undergoing clinical trials
#4 EPSTEIN BARR VIRUS
EB t'pical of herpes virus
Replicates in # l'mphoc'tes causing pol'clonal gro)th stimulation and l'mphoid h'perplasia
, results in immortalisation (ie continuall' dividing cell line)
, e"pression of nuclear neoantigens (E# nuclear antigen)
$irtuall' ui*uitous in health' adults )ho shed the virus in phar'ngeal secretions
Diseases7
0linical
!indngs
1+ Infectious Bononucleosis
, glandular fever
, incuation 6,G).s
, duration from fe) ).s to mths
, transmitted ' close contact .issing disease
, E#$ found in # l'mphoc'tes and epithelial cells in orophar'ngeal secretions
, most prevalent in seronegative children and 'oung adults
, letharg', anore"ia, fever (up to 6: - and 6: da's)
phar'ngitis (sore throat), e"udative tonsillitis, l'mphadenopath',
hepatosplenomegal', rash e"acerated ' ampicillin
, 0omplications(
(i) 1epatitis (fre*uent) E ma' have =aundice, anormal &!8
(ii) %neumonitis
(iii) Neurological( aseptic meningitis, encephalitis, m'elitis, optic neuritis, acute
cereellar ata"ia, <#4, peripheral neuropath', #ell/s %als'
(iv) 1aematological 9 hemol'tic anemia, thromoc'topaenia, splenic rupture
(v) 0$4 9 m'ocarditis, pericarditis
, Associations )ith 0ancer(
2+ #ur.itt/s l'mphoma
, occurs in areas )ith holoendemic malaria in tropical Africa
, %ersistent malarial infection thought to have immunosuppressive effect on
08 surveillance of E#$ transformed cells
, #& cells e"press E#$ mar.ers eg E#NA
, 0haracteristic 2 to 16 (or 2 to 22) chromosomal translocation
E deregulation of 0,m'c oncogene
5+ Naso%har'ngeal 0ancer
, strongl' assoc ) E#$
, N%0 cells harour integrated E#$ DNA and E#$ mar.ers
, 1igh anti,E#$ A in N%0 cf ctrls eg+ Ig< and IgA to $0A
6+ Immunolastic &'mphoma
, l'mphoproliferative disorder in patients )ith impaired 0B immunit'
(hereditar', P,lin.ed)
, immunodeficiencies and ac*uired immunosuppression (eg iatrogenicall'
induced in organ transplant recipients)
, pol'clonal immunolastic proliferation follo)ed ' monoclonal neoplasia
, mostl' e"tranodal
, fatal
K+ 0hronic fatigue s'ndrome
, e"treme fatigue, fever, sore throat, painful l'mphadenopath', muscle
)ea.ness, memor' loss
, reactivation of latent infectionQ
8ransmission 1. "aliva )pple wit$ a reactivation of latent infection as well as pple wit$ active
infection+
(. ,lood )rare+
Epidemiolog' I0C adults infected
fre8uency of clinically apparent infectious mononucleosis is $ig$est in t$ose
e!posed to virus later in life
%athogenesis
and Immunit'
4nfection first in orop$aryn!
&iraemia, infects , lymp$ocytes
CF cells react against , cells
3,& remains latent in , cells
A few copies of 3,& ;AA integrated into genome, many copies of circular ;AA in
cytoplasm
4mmune Response
, 1
st
4g/ Ab to t$e &CA
, 4g1 Ab follows and persists for life.
7 Aote' 4n addition to 3,& specific Abs, nonspecific $eterop$il Abs are also found.
4t does not react wit$ any cpt of 3,&
4t is li-ely t$at 3,& infection modifies a cell memb constituent suc$ t$at it
becomes antigenic
%eterop$ils H Abs detected by tests using Ags different from t$e Ags
t$at induced t$em
8reatment 4'mptomatic
Avoid penicillin ()ill cause rash)
E#$ vaccine undergoing clinical trials
No antiviral specific treatment
&a
Diagnosis
At'pical l'mphoc'tosis
, at'pical mononuclear cells
, at least 1:;
1eterophile As (%aul,#unnell test)
, 1aemagglutinating A to sheep R#0s
, A removed ' asorption )ith C" R#0 ut not )ith guinea pig .idne'
, %resent in R:;
, Bonospot screening test
R:; of health' adults have E#$ A
, E#$ IgB useful confirmation for IB
, As to E#$ antigens sa $0A, E# Nuclear Antigen, Earl' Ag7Diffuse, Earl'
antigen7restricted A+
#5 HUMAN HERPES VIRUS 6
1uman # l'mphotropic $irus
Criginall' isolated from patients )ith l'mphoproliferative disorders
1ealth' individuals have As and 11$6 in oral secretions
0linical features(
, associated )ith e"anthema (rash) suitum(no+ 6) a.a roseola infantum
, mild disease of children et)een 6 mths and 5 'rs, occasionall' confused )ith ruella
, incuation 1,2 ).s
, arupt onset, high p're"ia, l'mphadenopath', convulsions
, Ruelliform rash (after fever disappears) e"cept face
, &eucopenia )ith relative l'mphoc'tosis
, 4pontaneous recover'
, 11$ 6 in serum and throat )ashings during p're"ia
, Anti,p'retic agents to control fever (children 6 mths to 6 'rs )ith high fever prone to ferile fits and
convulsions)
#6 HUMAN HERPES VIRUS 7
Isolated from 0D6 positive 8 cells
4eroconversion in most children
$irus persists in saliva of GK; of normal adults
No association )ith human disease so far+
#7 HUMAN HERPES VIRUS 8 (AKA KAPOSI SARCOMA ASSOCIATED HERPES VIRUS)
J" most common cancer in A4;"
"e!ual transmission, organ transplant
, AB blood transmission
J" in A4;" is a malignancy of vascular endot$elial cells t$at contains many spindle s$aped cells and rbcs
, lesions are dar- purple, flat to nodular, at s-in, mout$, soles )but not palms+, 14F, lungs
%%& 8 also infects , cells, inducing proliferation primary effusion lymp$oma
POX VIRUSES
#1 SMALLPOX VIRUS
Disease 4mallpo" a.a $ariola $irus causes smallpo!
Important
%roperties
,ric- s$aped
Linear ds ;AA, dis--s$aped core wit$in a double membrane, lipoprotein envelope.
;AA dependent RAA pol
- re8uired as virus replicates in cytoplasm, no access to cellular polymerase
"ingle, stable serotype
Replicative
0'cle
>enetration, Encoating
&irion ;AA dpt RAA pol synt$esi:es early mRAA tt is translated into early, nonstruct
proteins, mainly en:ymes needed for subse8uent steps in viral replication
&iral ;AA replicated
F$en, late structural proteins made
Assembly and budding
8ransmission
and
Epidemiolog'
Aerosol
;irect contact wit$ s-in lesions
@omites
%athogenesis
and Immunit'
$irus infects HR8, local LA
%rimar' viraemia
Internal organs infected
4econdar' viraemia
4preads to s.in, virus replication, causing rash to appear suddenl'
(first 6 events occur during incuation period of 12 da's)
4evere infections ) 2:,K:; mortalit'
4mmunity following infection is lifelong, immunity frm vaccination lasts 10 yrs
0linical
!indings
"udden onset prodrome of fever and malaise
@ollowed by ras$, beginning on face and spreading all over body
/acules papules vesicles pustules crusts in ( to # w-s, leaving pin. scars
&a
Diagnosis
1rowing virus in cell culture or c$ic- embryos
;etecting viral Ags in vesicular fluid by 4@
%revention $accine
, )ith life, attenuated vaccinia virus prepared frm vesicular lesions produced in s.in of calves
and sheep7gro) in chic. emr'os
- Ab response is prompt, so e!posed person can still be protected
- inoculated intradermally
- side effects H encep$alitis, generali:ed vaccinia, vaccinia gangrenosa
- can be treated wit$ /et$isa:one
- Note( generall', complications range from mild r"ns to fatal encephalitis+ Cverall incidence
of complications is 172::, ut severe complications onl' 1K7million
1istor' Eradication of small po" )as possile for reasons as follo)s(
1. No other reservoir e"cept humans and primates
(. Cnl' acute infections )here patients
, die or
, recover )ith lifelong immunit'
, no carrier state or suclinical infection
#. $accinia virus is an effective immunogen
2. "mallpo! $as a single, stable serotype
.. Ab response is prompt, so e!posed persons can be protected w vaccination
0. Ao subclinical infections, easy clinical diagnosis. 3!posed person can be promptly
vaccinated.
#2 MOLLUSCUM CONTAGIOSUM VIRUS
Disease "mall, pin-, papular, wartli-e benign tumors of s-in or // 9 enign s.in nodules
Lesions wit$ c$aracteristic cup-s$aped crater wit$ w$ite core
7 Aote' t$ese are not warts, w$ic$ are caused by papillomaviruses
8ransmission
and
Epidemiolog'
0lose contact E (s.in to s.in), incl se", fomites
Disease *uite common in children, )orld)ide distriution
Lesions can be widespread in patients w reduced cellular immunity
4n immunocompetent patients, t$e lesions are self limited but may last for mont$s
Diagnosis 0linical diagnosis
0onfirmed ' EB (semi,solid caseous material can e e"pressed from the lesions)
8reatment Ao specific antiviral t$erapy
Ao vaccine
Removal or lesions by curettage or wit$ li8uid nitrogen often effective
0linical
findings
Incuation of 1 ). 9 6 mths
4mall papule gro)s into discrete, )a"', smooth, dome shaped, pearl' or flesh colored nodule
Hsuall' 1,2: lesions, occasionall' hundreds
Hsuall' enign and painless+ 4pontaneous recover'+
0hildren( trun. and pro"imal e"tremities
Adults( trun., puic areas and thighs
Iindividual lesions persist for 2 mths, disease lasts 6 mths
RNA ENVELOPED VIRUSES
FLAVIVIRUS
#1 DENGUE VIRUS
Important
%roperties
6 serot'pes (dengue virus sugroup)
Envelope gl'coprotein contains antigenic determinants
, group specific
, sugroup specific
, t'pe specific
0ontains nonstructural proteins
, eg serine protease to chop proproteins for virus replication
%athogenesis
Dengue virus deposited in s.in ' iting mos*uito vector
$irus replicates initiall' at site of infection and in local l'mphatic tissue
$iraemia )ithin a fe) da's (lasts up to 6
th
or K
th
da' after onset of s'mptoms)
$irus replicates in mononuclear phagoc'tes
, histioc'tes, B%s, .upffer cells, monoc'tes
2 h'potheses on pathogenesis of D1!7D44(
1+ $iral virulence 9 dengue virus strains var' in pathogenic potentialF severe
complications caused ' virulent strains
2+ Immune enhancement involving infection,enhancing As
D44 seen in 2 grps of patients(
(i) Infants less than 1 'r )hile e"periencing primar' dengue infection
- Note( if mom has dengue, Ig< passes across placenta to a'+ If a'
gets dengue, immune response mimics secondar' infection
(ii) 0hildren 1 'r and aove )hile e"periencing a second dengue infection
(ma=orit')
In the first infection group,
, infants in 1
st
6 mths protected ' maternal dengue neutrali?ing As
, As maternal Ig< degrades, dengue neutrali?ing As decrease to elo)
protective level, )hile As )ith enhancing activit' reach pea. level
, Infant e"posed to dengue virus at this stage is at high ris. of developing
D44
, !urther Ig< degradation results in decrease of enhancing activit' 9
as'mptomatic infection
In the second group,
, non,neutrali?ing enhancing As rapidl' produced
, forms immune comple"es )ith replicating virus
, Immune comple"es attach to !c receptors on mononuclear phagoc'tes
, Immune comple"es internali?ed
, $irus continues to replicate in infected cell
, Boile cells spread infection+
, Infection activates mononuclear phagoc'tes, releasing factors responsile
for increased vascular permeailit' and disorder in haemostasis(
(i) en?'mes cleaving 05, releasing anaph'lato"ins
(ii) leu.oc'te thromoplastin causing haemorrhage
(iii) activation of complement s'stem
- Note( Immune enhancement phenomenon
, e"plained ' antiod',dependent enhancement of infectivit'
, mediated ' cross,reactive ut non,neutrali?ing dengue viral As
, leads to a rapid cascade of complement activation, e"cessive
production of vasoactive c'to.ines, and other chemical mediators
(e+g+ histamine, t%A etc)
7 According to Levinson'
- >atient recovers frm classic dengue caused by 1 of t$e 2 serotypes
- Ab against tt serotype produced
- >atient infected wit$ anot$er serotype
- An anamnestic, $erotypic response occurs, and large amts of cross-
reacting Ab to t$e 1
st
serotype are produced
- Fwo $ypot$eses abt w$at $appens ne!t
)i+ 4mmune comple!es composed of virus and Ab are formed t$at
activate complement, causing increased vascular permeability and
t$rombocytopenia
)ii+ Abs increase t$e entry of virus into monocytes and />s wit$ t$e
conse8uent liberation of a large amt of cyto-ines
Antiod'
Responses and
Immunit'
!irst Infection
, %rimar' t'pe A response
, Initiall' IgB A (transient)F A produced against t'pe,specific Ag
determinants (neutrali?ing)
, Ig< follo)s, neutrali?ing
, %atient immune to infecting serot'pe, partial protection (5,6).s) against
other serot'pes
4econd infection
, Ig< predominant
, A produced against group or sugroup specific Ag determinants, non
neutrali?ing and infection enhancing
Diseases and
0linical findings
As'mptomatic reservoirs in 2K; of infections
4IB%8CB4(
Hndifferentiated fever (infants and 'oung children)
0lassic dengue (rea.one fever)
, egins suddenl' )ith an influen?a li.e s'ndrome
E fever, malaise, cough, headache, pain ehind e'es
, severe pains in muscles and =oints
, enlarged &N, a maculopapular rash, and leu.openia are common
, after a )ee. or so, s'mptoms regress ut )ea.ness ma' persist
, rarel' fatal, fe) se*uelae
Dengue 1emorrhagic !ever7Dengue 4hoc. 4'ndrome
, 1:; mortalit'
, initial picture same as classical dengue
, acute onset fever, high, continuous, lasting 2,G da's
, hemorrhagic manifestations, including at least a positive tourni*uet test+
E %etechiae, purpura, ecch'mosis
E Epista"is, gum leeding
, E 1armatemesis and7or malaena, hepatomegal' ma' e present
, later shoc. and hemorrhage )ith leeding esp into <I8 and s.in develop
, Dengue 4hoc. 4'ndrome
, occurs at a time of, or shortl' after, fall in temperature, et)een 5
rd
and G
th
da' of disease
, acute adominal pain is a fre*uent complaint shortl' efore onset of
shoc.
, patient dies )ithin 12,26 hrs or recovers rapidl' )ith antishoc. therap'
, )arning signs of shoc.( restlessness and7or letharg', acue adominal
pain, cold e"tremities, s.in congestion, oliguria
, rapid and )ea. pulse )ith narro)ing of pulse pressure (2:mm1g or less)
or h'potension, )ith cold, clamm' s.in and restlessness
&A# 0riteria for D1!7D44
thromoc'topaenia S1:::::7mmT5
increase in hematocrit ' 2:; or more of recover' value (due to
haemoconcentration+ %lasma reduced due to lea.age of plasma due to
increased vascular permeailit'+
(#reathlessness ma' occur due to pleural effusion)
- Note( third and 6
th
infections usuall' mild
Banagement of
D1!7D44
Ba=or patho anormalit' is an acute increase in vascular permeailit' that leads
to lea.age of plasma
%rognosis depends upon earl' recognition of shoc., ased on careful
monitoring of pulse and #%
#asic principle in management of D44 is correction of plasma lea.age '
volume replacement 9 infusion of plasma, plasma e"pander )ith electrol'te
solution
4alic'lates s+a+ aspirin that is ulcerogenic should e avoided+ Hse paracetamol
instead
8ransmission Aedes Aeg'pti mos*uito (also the vector of 'ello) fever virus)
Aedes Alopictus is another vector+
1uman reservoirs, ut a =ungle c'cle involving mon.e's as the reservoirs and
other aedes species as vectors is suspected
Epidemiolog' Classic dengue in tropical areas worldwide
;engue $emorr$agic fever particularly in "out$ern Asia
&a diagnosis &ive mos*uitoes( aedes spp (adults), to"orh'nchites spp (adults, larvae)
, cell cultures ( 06756 mo??ie cell line, mon.e' .idne' cell lines ($ero, &&0,
B32)
, 4uc.ling )hite mice (1,2 da's old)
4erologic tests
- demonstrate t$e presence of 4g/ antibody or a 2-fold or greater rise in Ab
titer in acute and convalescent sera
, 1aemagglutination inhiition test
, IgB and Ig< E&I4A
,
8reatment Ao antiviral t$erapy available
%revention Ao vaccine available
4nsecticides
;raining stagnant water
>ersonal protection
la) enforcement, health education
#2 APANESE ENCEPHALITIS
Important
%roperties
Cne serot'pe
%athogenesis Infection follo)s ite ' infected mos*uito
$irus replicates locall' either in s.in, l'mphatics or endothelium of #$
8ransient viraemia
- Note( If viraemia terminates efore virus penetrates rain, or efore virus
destro's enough rain cells to produce overt encephalitis, infection )ill e
as'mptomatic or merel' a non,encephalitic, generali?ed, ferile sic.ness
$irus enters nervous s'stem either(
, ' capillar' seeding through endothelium into meninges and rain
, through infection of nerve endings (s+a+ NBAs of olfactor' receptors)
)ith suse*uent a"oplasmic transport to neurons
8ransmission Bo??ies (vector) incl+ 0ule" tritaeniorh'nchus and 0ule" gelidus
%igs7#irds(amplif'ing hosts)Bo??iesBan (incidental host(dead end))
ENJCC8I0 c'cle
0linical disease Arupt onset )ith fever, headache, malaise, dro)siness, vomiting, generali?ed
convulsions
Bar.ed and increasing disturances of sensorium and signs of meningeal
irritation (nec. rigidit', positive 3ernig/s sign)
04! anormalities( pleoc'tosis, elevated glucose content, raised protein
Bortalit' ranges from S1:; in endemic areas to 2:,2K; in severe epidemics
1istopatholog' of rain(
, destruction of neurons and glial cells
, perivascular infiltration )ith l'mphoc'tes (perivascular cuffing)
, sometimes focal hemorrhage
4e*uelae common in survivors( motor )ea.ness, mental ac.)ardness,
ehaviour disorders (apath', aggressiveness)
Epidemiolog' K::,1::: inapparent infections for ever' encephalitis case due to effective
###
0ases usuall' in children under 1K'rs
Epidemics in India, 8hailand, $ietnam, 0hina
&a Diagnosis Immune response primaril' humoral
,A develops at or shortl' after onset of 0N4 disease 9Ig< and IgB
IgB in 0N4 during encephalitis, appears in 04! and serum
IgB captures E&I4A
%revention and
0ontrol
Inactivated vaccines derived from infected mouse rain
No antiviral therap'
BUNYAVIRUSES
#1 HANTAVIRUSES
Important
properties
8risegmented single stranded RNA genome
Diseases 1aemorrhagic fever )ith renal s'ndrome
, 3no)n viruses( 1antaan, 4eoul, %uumala, Dorava
, Bild to severe
, 4evere disease in 3orea, 0hina+ Also in the #al.ans (Dorava $irus)
, 4evere 1!R4 clinical course divided into K phases(
1+ !erile
2+ 1'potensive
5+ Cliguric
6+ Diuretic
K+ 0onvalescent
, 4udden onset )ith influen?a li.e s'mptoms, petechiae and con=unctival
hemorrhage
, after 5,G da's, 1'potensive phase egins E )ith tach'cardia, vomiting,
shoc. and further hemorrhagic signsF la findings include
haemoconcentration, thromoc'topaenia, leu.oc'tosis
, Cliguric phase E accompanied ' h'potension and severe harmorrhage,
anormal renal function+ Electrol'te imalance ma' occur during diuretic
phase+
, 0onvalescent phase prolonged
, Bost deaths in oliguric phase
, Bild 1!R4 in Europe also called nephropathia epidemica (%uumala
virus)
, 5 1!R4 patients seen in 4ingapore( one had an influen?a li.e illness and
renal d'sfunctionF second had petechial s.in rash, severe
thromoc'topaenia, proteinuria and hepatitis, third had the classical K,
phase clinical course )ith 0N4 complication
, mortality 10C
, Bccurs in Asia and 3urope but not A America
1antavirus %ulmonar' 4'ndrome
, 3no)n viruses( 4in Nomre
, !ever, m'algia and variale resp s'mptoms eg+ 0ough follo)ed '
arupt onset of acute resp distress
, Aot transmitted from person to person
, 4t is a new virus t$at occurred in 1II#. virus endemic in deer mice in
western E"
, @ew pple $ave Ab against virus, indicating t$at asymptomatic infections
are not common
, /ortality 00C
8ransmission $irus transmitted to humans ' infected rodents
Epidemiolog' Each 1antavirus is maintained in nature ' infecting a single rodent species
Infection in rodents as'mptomatic and lifelong
4heds virus in saliva, urine, faeces
8ransmission to humans occurs predominantl' after infected rodent e"creta are
inhaled
Inapparent infections common
&a diagnosis IgB ' indirect I! assa' and E&I4A
8reatment and
prevention
Ao effective drug and no vaccine
ORTHOMYXOVIRUSES !"#$% &'&(') *+ INFLUENZA VIRUS,
1::nm particle
Envelope
, composed of lipoprotein
, covered )ith radiall',pro=ecting gl'coprotein surface spi.es
,
Diseases 4nfluen:a A Kworldwide epidemics )pandemics+ of influen:a
4nfluen:a , K ma9or outbrea-s. >eriodic epidemics.
4nfluen:a C K mild RF infections, no ma9or outbrea-s
Important
%roperties
&irus contains an RAA dependent RAA polymerase w$ic$ transcribes Kve
genome into mRAA. F$erefore genome not infectious
2 discrete RNA segments randoml' incorporated into virion during maturation
5 t'pes of RNA pol
Lipoprotein envelope covered by radially pro9ecting glycoprotein surface
pro9ections, a $emagglutinin and a neuraminidase
(i) 1 E inds to cell surface R and initiates infection
, agglutinates rc in la tests (inhiited ' As, 1I)
- target of neutrali:ing Ab
, t'pe (A, #, 0) and strain specific antigen9 antigenic variation
(ii) N E acts on neuraminic acid R
, cleaves neuraminic acid )sialic acid+
, to release progeny virus from infected cell
- degrades t$e protective layer of mucus in t$e RF
D en$ancing t$e ability of t$e virus to infect R3
4nfluen:a A esp $as a $ig$ capacity to c$ange Ag of % and A proteins
(i) Antigenic shift
, recomination of RNA segments of t)o Ag t'pes simultaneousl' infecting
the same cell t) diff animal virus strains
, ' genetic reassortment, entire segments of RNA are e"changed, each of
)hich codes for 1 protein Ba=or Ag change of oth surface cpts+
(ii) Antigenic drifts
, minor changes ased on spontaneous mutations in genome RNA
, lead to minor changes in 1+
%ave group specific and type specific Ags
, the internal rionucleoprotein contains solule or Us/ antigen that is grp
specific tt distinguishes A # and 0+ 0!8+
, t$e % and A are type specific, on cell surface

- Note( , A against 1 neutrali?es the infectivit' of virus D prevents diseases+
, A against grp specific Ag does not
, A against N, does not neutrali?e
, ut reduce disease (limit viral replication D spread)
/any animal species $ave t$eir own influen:a A viruses
, F$ese viruses are t$e source of RAA segments for Ag s$ifts
, eg. 4f avian and $uman virus infect t$e same cell in farmer<s RF,
reassortment may occur and a new variant of $uman A bearing avian %
may appear
4nfluen:a , is only a $uman virus, no animal source of new RAA, t$erefore Ag
drift but no s$ift
Replication &irus adsorbs to cell w$en it interacts wit$ sialic acid R on cell surface
3ndocytosis, uncoating
&irion RAA polymerase ma-es mRAA
, virion proteins in cytoplasm
>rogeny RAA genomes made in nucleus
,udding

7 Aote' 4& and retro&s are t$e only RAA viruses t$at $ave impt replicative step in
nucleus
8ransmission Airborne Resp droplets
7 Aote' Ability of 4A to cause epidemics is dependent on Ag c$anges in % and A
, 4A s$ifts 10-11yrs
, 4A drifts 1 yr
, >ree!isting immunity in most pple are not effective
/ainly in winter. >redisposes to secondary bacterial pneumonia
%athogenesis
and
Immunit'
A degrades protective mucus in ERF and LRF
- Allow virus to gain access to cells
7 Aote' 4nfection limited primarily to t$is area as proteases t$at cleave % to
activate it are located $ere
;espite systemic symptoms, viraemia is rare
)eg. "evere myalgias are due to circulating cyto-ines+
$iral multiplication in RE )ith des*uamation and ciliar' damage
4& pneumonia, w$ic$ can complicate 4, is interstitial in location
4mmunity mainly upon 4gA
D 4g1 also produced but less protective
0linical
findings
Ba=or epidemic disease )ith occasional pandemics
Incuation 1,6da's
4udden fever, m'algias, headache, malaise
Rhinorroea, snee?ing
4ore throat, cough
"ymptom usually resolves spontaneously in 2-5 days
0omplications(
1+ Influen?al7#acterial %neumoniae
, primar' viral virus moves frm ERF to lungs infection resp failure+
Rare ut high mortalit'
, secondar' acterial after damage of ronchial mucosa
, predisposing factors are( e"tremes of age, immunocompromised, chronic
cardiopulmonar' diseases
, streptococcus pneumoniae, haemophilus influen?ae, staph'lococcus aureus
- Note( indication for antiiotics+ 0an give as preventive measure during flu to
high ris. group even if pneumonia has 'et to develop+
2+ B'ocarditis
, presents wit$ c$est pain, giddiness due to lac- of cerebral perfusion.
, advice patient to rest
5+ B'ositis
, inflammation of t$e muscle
6+ Re'es 4'ndrome
, 0ereral oedema Vliver degeneration
, Rare, fatal
, !ollo)s some viral infections (such as I# and $J$)
, 1igh mortalit'
- Note( Aspirin used to lo)er fever has een lin.ed to pathogenesis
8reatment Amantadine
- Freatment and prevention of 4A in confined, elderly, unimmunised population
- ( drawbac-s )i+ to!ic K use only for very sic- patients
)ii+ prone to resistance - not useful towards %.A1
Rimantadine - less side effects
*anamivir )Relen:a, in$alant+ and Bseltamivir )tamiflu,oral+
- A in$ibitors
- for 4A and 4, reduces duration of symptoms by 1-(days
%revention &accine
)i+ -illed A and , strains
, doesn<t infect R3, t$erefore no 4gA
, but 4g1 confers from protection, but titer also low
, protection lasts only 0 mt$s

)ii+ split virus or purified surface Ag
, used esp in -ids due to decreased side effects
)iii+ e!perimental temperature sensitive mutant
, infects ERF )##7+ but inactivated in LRF )#57+
, t$erefore does not cause disease and yet induces 4gA
&a Diagnosis $irus isolation
, chic. emr'o, mon.e' .idne' cells (no 0%E ut haemadsorption
affected cells )ill asor haem), t'ping ' 11
, I! of Ag in RE cells
4erolog'
, eg 0!8 (complement fi"ation test)
, not useful+ Ban' of us have had flu, )ill have A an')a'
Banagement Differential diagnosis
4'mptomatic treatment
Recogni?e and treat complications
Inactivated vaccine proph'la"is for high ris. groups during )inter
prolems of timel' preparation(Lcatching up vaccineM), short lived
immunit', incomplete protection, rarel' <# s'ndrome
Binimi?e spread ' respirator' route
PARAMYXOVIRUSES
Enveloped helical RNA viruses
<enetic recominations uncommon
RAA depentdent on RAA pol to turn Kve RAA to mRAA
3nvelope covered wit$ spi-es, w$ic$ contain eit$er %, A, or a fusion protein t$at causes cell fusion and in
some cases, $emolysis
/embers pat$ogenic for $umans( parainfluen?a, respirator' s'nc'tial, measles, mumps
#1 PARAINFLUENZA VIRUS
Diseases Infects animals and man, infection ac*uired ' age K
, 8'pe 1 croup in infants
, 8'pe 2 epidemics in )inter
, 8'pe 5 #ronchiolitis and ronchopneumonia in 'oung infants, croup in
older infants
, 8'pe 6 minor resp infection
, 1o)ever, there is considerale overlap
1+ 0roup (acute lar'ngotracheoronchitis)
, cough, hoarseness
, if severe, d'spnoea, stridor, c'anosisma' re*uire tracheostom'
, differential diagnosis diphtheria, haemophilus influen?ae and epiglottitis
mimic croup
2+ #ronchiolitis
5+ #ronchopneumonia
6+ !erile common cold
, disease resembling common cold in adults )often caused by type 2+
, ferile, sore throat, cough, hoarseness
Important
%roperties
"urface spi-es consist of %, A )on same spi-e+ and @
2 types
- >4& # causes diseases less fre8uently
7 Antibodies to eit$er % or @ neutrali:es infectivity
8ransmission Resp droplets
%athogenesis
and Immunit'
ERF and LRF disease wit$out viraemia
Large proportion of infections are subclinical
&a diagnosis 8issue culture
, mon.e' .idne' cells 0%E ' t'pe 2
, guinea pig R#0 haemagglutination (haemadsorption)
Antigenic detection
, I! of infected RE cells
4erolog' (not so useful)
, detect antiodies to 4olule antigen (earl') $iral antigen late
, 0!8, 1I, N8
8reatment and
0ontrol
No antiviral agent availale
$entilator' support
Antiiotics for 2- acterial infection
4edation and h'dration (to overcome fluid loss via h'perventilation)
No vaccine
#2 RESPIRATORY SYNCTIAL VIRUS
Diseases Bost impt cause of ronchiolitis in infants
, pea. at 5 mths (during )inter)
, cough, fever, d'spnoea, tach'pnoea, )hee?ing, c'anosis, inspirator'
indra)ing of resp muscles
, pneumonia ma' develop after this
, immune,mediated and7or mechanical ostruction of narro) ronchioles '
inflammator' process
, 0omplications
(i) secondar' acterial infections
(ii) otitis media
(iii) cardiac failure
(iv) apnoea (Ucot death s'ndrome/)
, up to K; mortalit' in ronchiolitis and pneumonia high mortalit' assoc
) 0N4 malformations and congenital diseases of heart and lung
in older children and adults, HR8 infection t$at resembles common cold
- 7 Aote' Bur lumen is bigger, t$erefore less severe diseases
Important
properties
"urface spi-es are fusion proteins K forms multinucleated giant cells
No 1 or N
Ab against fusion protein neutrali:es infectivity
8ransmission Resp droplets
;irect contact of contaminated $ands wit$ mout$ or nose
R"& causes outbrea-s of RF infections yearly, unli-e ot$er Lcold< viruses, w$ic$
reenter t$e community every few years
%athogenesis
and Immunit'
R"& in infants more severe, more often involves LRF
- maternal Abs react wit$ virus and damage RF cells can result in severe
pneumonia &iral-Ab comple! deposited on resp tract of c$ild, complement
activated inflammation
Ao viraemia
/ost individuals $ave multiple infection caused by R"M, indicating incomplete
immunity
8reatment and
0ontrol
Aerosolised Riavirin
, for severel' ill infants
, ut there is uncertaint' regarding its usefulness
0oncurrent therap' )ith 1'perimmune gloulins ma' e more effective
No vaccine
Isolate hospitali?ed children )ho are infected
&a diagnosis 8issue culture
, inoculate 1e&a or 1ep,2 cells
, highl' characteristic refractile s'nc'tium formation of multinucleated giant
cells
$iral antigen demonstration (al)a's the fastest, est )a')
, I! of nasophar'ngeal aspirate
4erolog'
, one serot'pe
, 0!8, 1I, N8
#3 MEASLES VIRUS
Important
%roperties
Fwo types of spi-es
, %
, @usion and $aemolytic
"ingle serotype
% is t$e Ag against w$ic$ Abs are directed
8ransmission Aerosol, resp droplets during prodromal period and 2,5 da's after rash starts
outrea.s 2,5 'rs
)ithout vaccination, infection ' age K
%athogenesis
and immunit'
After infecting ERF cells, virus enters lood, infects RE cells, w$ere it replicates
again
"preads via blood to s.in
Ras$ is primarily due to CF cells attac-ing measles virus infected vascular endo
cells in s-in
"$ortly after ras$ appears, t$e virus can no longer be recovered and t$e patient
can no longer spread t$e virus to ot$ers
/ultinucleated giant cells form as a result of fusion protein in spi-es
&ifelong immunit' in natural infection
, 4g1 places a role in neutrali:ing in viraemic stage
, C/ also plays a role
4nfection wit$ measles can transiently depress C/ against ot$er 4C /os. Can
cause reactivation of latent /B
, measles bind to C;20 receptor on macrop$ages
, >roduction of 4L-1( suppressed
0linical
findings
Incuation 1:,16 da's
>rodromal p$ase
, fever, con=unctivitis (causing photophoia), rhinnorhoea, cough
1+ 3opli./s 4pots
, around parotid duct orifice heralds onset of rash
, right red lesions ) )hite central dot located on uccal mucosa diagnostic
2+ Baculopapular Rash
, fe) da's later, maculo(flat)papular(protruding) rash
, on face first, then proceeds to e"tremities
- pigmentary c$anges after ras$
- $ypo, $yper sometimes.
- not permanent
0omplications
(i) %ost infectious dem'elinating encephalitis
, in 171::: cases
, 1:; mortalit'
, 6:; permanent se*uelae
2+ <I8
, diarrhoea due to measles virus or secondar' acterial infection
5+ Bucosal infections
, acterial otitis media
, con=unctivitis
6+ Respirator'
, ronchopneumonia
, primar' measles (giant cell) pneumonia
E rare progressive measles lung infection in immunocompromised or
malnourished
, secondary bacterial pneumonia
K+ 4uacute 4clerosing %anencephalitis (ver' rare)
, fatal disease of 0N4 that occurs several 'rs after measles
, persistent latent infection of neurons ' defective measles $Q
, anormal immune response to measles $Q
, impaired host immunit'Q
, m'oclonic sei?ures, intellectual deterioration, suppression ust EE<
pattern, c'toplasmic inclusions in neuronal cells
6+ Implicated in Bultiple sclerosis
8reatment Ao antiviral t$erapy available
%revention &ife, attenuated vaccine
, onl' at 1K mths in ne)orns cause efore 1K mths maternal A in child can
neutrali?e the virus
, mil. p're"ia ut serious complications are rare
, ooster dose re* as immunit' )anes
- IB%CR8AN8( , 3illed vaccine shld not e used
, 3no)n to e still infective+
%assive Immuni?ation
, )ith immune gammagloulin for contacts ) immunodeficienc' eg leu.aemia
&a diagnosis 8issue culture
, virus isolated from phar'n", con=unctiva, urine
, infected mon.e' .idne' cells demonstrate multinucleated giant cells
4erolog'
, measles IgB assa' for recent infection
, measles Ig< for retrospective diagnosis
#4 MUMPS VIRUS
Important
%roperties
( types of envelope spi-es
- one wit$ % and A
- t$e ot$er wit$ fusion and $emolytic activities
"ingle serotype
Ab against %
8ransmission Resp droplets
pea- incidence in winter
#0C subclinical infection w$ic$ confers immunity
most infections t) K,1K 'rs
%athogenesis 1. ERF ,lood parotid glands, testes, ovaries, pancreas, meninges
(. ,uccal mucosa up stensen<s duct parotid gland
Lifelong immunity D Enilateral doesn<t mean t$e ot$er side will follow
0linical
!indings
Incuation 12,21 da's
%rodromal stage
, fever, malaise, anore"ia, tender s)elling of salivar' gland (esp parotid)
ma' have tender cervical l'mphadenopath'
Disease is t'picall' enign Eresolves spontaneousl' in 1 )ee.
0omplications (more fre*uent in adults)(
(i) Crchitis
, in 1:,2K; of post puertal males
, usuall' unilateral
, firous tunica aluginea resists e"pansion, pain and s)elling
E pressure necrosis of spermatoc'tes
, ilateral ma' lead to sufertilit'
(ii) Aseptic meningtitis
, common, usuall' enign, self,limited, )ithout se*uelae
(iii) %ancreatitis (in 1:; of adults)
(iv) B'ocarditis, nephritis, oophoritis, th'roiditis, dem'elinating encephalitis,
arthritis Rare
8reatment Ao anti viral t$erapy available
%revention Live, attenuated vaccine
>rotection up to 10 yrs
1iven at 1 yr old
&a Diagnosis 4pecimens
, saliva, throat )ashings, urine, 04!
8issue culture
, using mon.e' or 1e&a cells or 1en/s eggs
, 0%E 9 rounding of cells
, multinucleated s'nc'tial formation
, eosinophilic inclusions
, haemagglutinates chic. rc
4erolog'
, IgB, Ig<, 0!8, 1I, N8, E&I4A (commonl' used)
TOGAVIRUSES
#1 RUBELLA VIRUSES
Ruivirus of 8ogavirus famil'
4mall RNA virus enveloped )ith cuic s'mmetr'
An acute, usuall' enign, infectious disease caused ' a togavirus and most often affecting children and
nonimmune 'oung adults, in )hich the virus enters the respirator' tract via droplet nuclei and spreads to the
l'mphatic s'stem+
It is characterised ' a slight cold, sore throat and fever, follo)ed ' enlargement of the postauricular,
suoccipital and cervical l'mph nodes and the appearances of a fine pin. rash that egins on the head and
spreads to ecome generalised+
Diseases and
clinical
findings
0ommon viral e"anthem easil' confused )ith others
Cften suclinical esp in children
Incuation 16,21 da's
0onstitutional s'mptoms often mild ut variale
#rief prodromal period
, fever and malaise, headache, con=unctivitis, cor'?a(common cold s'mptoms),
cough, l'mphadenopath'
1+ !orschheimer/s 4pots
, herald onset of s.in rash
, discrete rose spots on palate
2+ <erman Beasles
, maculopapular rash, starting on face e"tremities lasting W5da's
5+ 8ender &'mphadenopath'
, fre*uentl' suoccipital, postauricular and cervical nodes
0omplications(
(i) pol'arthritis
- in adults, esp women caused by immune comple!es is common
, affects one or more large and small =ts )hen rash susides
, arthralgia (=oint pain)
(ii) encephalitis
, uncommon+ AdultsOchildren
, occasionall' fatal
(iii) purpura
, thromoc'topaenia and hemorrhage
6+ 0ongenital Ruella 4'ndrome
, teratogen esp in 1
st
trimester
, mainl' affects organogenesis of
(i) heart (%DA, $4D, %4)
(ii) e'es(cataracts, retinopath', microphthalmia)
(iii) rain (deafness, mental retardation, microcephal', spasticit'),
, Interstitial pneumonitis,
, DB
, 1epatosplenomegal'
, 8hromoc'topenia, metaph'seal osteitis
- Note( ris. and e"tent of emr'opath' greater esp during earlier periods of
organogenesis
, 55; in 1
st
mth of pregnanc', 2K; in 2
nd
, R; in 5
rd
, 6; in 6
th
,stillirth, spontaneous aortion
, "ome c$ildren infectd in utero can continue to e!crete rubella for mt$s aft birt$
- "ome congenital s$edders can be asymptomatic and wit$out malformations
Important
%roperties
"urface spi-es wit$ %
"ingle Ag type
, one serot'pe
- but got many different strains
Ab against % neutrali:es it
8ransmission 1+ Resp droplets
2+ 8ransplacental
recurrent spring endemics )ith increase in susceptile population in countries
)ithout vaccination+ 0R4 urden is heav' on societ'+
)orld)ide distriution+
moderatel' infectious
%athogenesis
and Immunit'
4nitial replication in Aasop$aryn! and local LAviraemia organs and s-in
Brigin of ras$ is unclear, may be due to Ag-Ab mediated vasculitis
8reatment Ao antiviral t$erapy available
%revention Live, attenuated vaccine
- long lasting at least 10 yrs
- few side effects
&a diagnosis 8issue culture
, virus isolation is time consuming
4erolog'
, for detection of significant rise in A tire and7or IgB up to one month after
rash
, 1aemagglutination inhiition
, E&I4A
, Radial haemol'sis in gel
, I!
, %assive agglutination
, RIA
, %art of 8CR01 Ig< panel
Banagement
and control
Xuarantine infected person
%assive immunogloulins
4creening
&ive attenuated ruella vaccine at 1 'r of age in 4ingapore
,adverse effects of vaccine N fever, rash, l'mphadenopath', arthralgia,
arthritis, rarel' pol'neuropath'
, advise against pregnanc' )ithin 5 mths follo)ing vaccination ecause it is
a live vaccine
CORONAVIRUSES
Important properties 0ro)n li.e pro=ections on virion surface
1aemagglutinate R#0s
At least 5 Ag t'pes )ith some cross reactivit'
8wo serotypes
Diseases Bucosal infections in domestic animals
0ommon colds in man (at 1K; of total),
- 9ust second to r$inoviruses in fre8uency
- c$aracteri:ed by cory:a )i.e. r$inorr$ea+, scratc$y sore t$roat, low
grade fever.
, Lasts several days
- Ao se8uelae
in (00(, a new disease, an atypical pneumonia called "AR" )"evere acute
resp syndrome+ emerged
- 1enome se8uence of t$e coronavirus t$at caused t$e "AR" outbrea- is
different from t$e e!isting $uman strains
- fever of at least #8C
- non productive coug$
- dysnea
- $ypo!ia
- c$ills, rigors, malaise, $eadac$e are common
- sore t$roat and r$inorr$ea are uncommon
- c$est Nray reveals interstitial Lground-glass< infiltrates t$at do not
cavitate
- leu-openia and t$rombocytopenia are seen
- incubation ( to 10 days
%athogenesis and
Immunit'
4nfection is typically limited to t$e mucosal cells of resp tract
O.0C asymptomatic K role t$ey play in transmission is unclear
4mmunity following infection is brief, reinfection can occur
Replicative c'cle &irus adsorbs to cells via % spi-es
3nters cytoplasm, uncoated
?ve genome translated into polypeptides, self-cleaved by virus encoded
protease
Fwo of t$ese peptide aggregate to form RAA pol t$at replicates genome
4n addition, mRAAs are synt$esi:ed, t$en translated into structural proteins
&irus assembled and membrane obtained from 3R
&a diagnosis 8issue culture
, human coronaviruses hard to culture
, isolated in human emr'o trachea cultures
, 0%E in human emr'o lung cell line
4erolog' and %0R tests for 4AR4
8reatment and
0ontrol
No treatment
)t$oug$ a combination of ribavirin and steroids $as been tried in t$e
treatment of life-t$reatening "AR", but t$eir efficacy is uncertain+
No vaccine
RHABDOVIRUSES
#1 RABIES VIRUS
JCCNC4E4 9 diseases of verterate animals that can e transmitted to man, either directl' or indirectl'
through an insect vector (arovirus) eg+ #ird flu, 4AR4, nipah virus (ats), raies
Disease Raies 9 an acute infection of the 0N4
Important
properties
Bemer of &'ssavirus genus or the Rhadoviridae famil'
15:,26: nm
ssRNA(,), ullet shaped capsid, lipoprotein envelope, RNA dependent RNA pol
Bne serotype, Ag in env 1> spi.es (6,Gnm)
,road $ost range K all mammals
Replicative 0'cle Attac$es to Ac$-R on cell surface
&irion RAA pol synt$esi:es . mRAAs t$at code for viral proteins
Replication of progeny RAA by virus encoded RAA pol
Assembly and budding
8ransmission and
Epidemiolog'
,ite of a rabid animal t$at manifests aggressive, biting be$avior induced by t$e viral
encep$alitis
Aerosols of bat secretions
%revalent in )ildlife, eg mongoose, dogs, antelopes, fo"es, ats, raccoons
%athogenesis and
Immunit'
$irus multiplies locall' at ite site in the striated or connective tissue, enters peripheral
N through NBA, spreads to 0N4(esp rain) in endoneurium of sch)ann cell ' a"onal
transport
8erminall', there is )idespread 0N4 involvement
;uring its transport, virus s$eltered from immune system and little, if any, immune
response mounted
&irus multiplies in CA" and t$en travels down perip$eral nerves to salivary glands and
ot$er organs
Ao viraemia.
Pit$in t$e CA", encep$alitis occurs
- wit$ deat$ of neurons and demyelination
, infected neurons contain an eosinop$ilic cytoplasmic inclusion called a Aegri
,ody
%ig$ mortality
Infectivit' depends on site and mode of transmission
, If itten on head, 6:; ris.+ 1and, 1K,6:; ris.+ &eg, 5,1:; ris.
0linical !indings Incuation varies, according to location of ite, 2 toO16 ).s
, shorter )hen ites on head cf ites on leg due to shorter distance of virus travel
%rodrome
,1,2da's
, nonspecific s'mptoms (such as fever, anore"ia)
, pain and paraesthesia at ite site
, <I8 and HR8 s'mptoms
, irritailit', apprehension, sense of impending death, h'drophoia
7 Aote' painful spasms of t$roat muscles on swallowing K resulting in $ydrop$obia, an
aversion to swallowing water because it is so painful
E"citation phase(
, h'perventilation, h'peractivit', disorientation, sei?ures
%aral'tic phase ()ithin a fe) da's)(
, letharg', increased salivation,
, earl' paral'sis
, esp in areas innervated ' 0N
, in somatic muscles, ladder and o)els
, <radual involvement of cardiac muscles and paral'sis of resp muscles+
deat$ almost invariably ensues
&a Diagnosis In animals
e!amination of brain tissue by 4@ Ab to rabies virus
$istologic staining of negri odies (pathognomonic on histolog' in G:; cases) in
c'toplasm of hippocampal neurons
In humans
I!,A (direct fluorescent A test D!A) of iops' specimen ta.en frm s.in of nec. at the
hairline, or corneal impressions, to test for virus antigen
isolation of virus and cultivation from sources s+a+ saliva, spinal fluid, rain tissue
, most definitive means of diagnosis, ut rarel' offered ' diagnostic las
4erolog'
, circulating A appear slo)l' in course ut usu present ' onset of clinical
4'mptoms
, rise in Ab titer to virus
- Aegri bodies in corneal scrapings and autopsy specimens of brain
8reatment Ao antiviral t$erapy
%revention Rabies vaccine K . doses on days 0, #, 5, 12, #0. ,oosters to maintain titer of 1'.
, can be used pre or post e!posure due to long incubation period
, inactivated )hole virus vaccine grown in $uman diploid cells (1D0$) est
vaccine availale, efficac' nearl' 1::;, rarel' an' severe r"ns
, given IB or 40 into deltoid area of upper arm
, dogs are given inactivated vaccies
%oste"posure
, immediate cleaning of )ound )ith soap and )ater to reduce viral load
, proph'la"is E oth vaccine D human raies Ig (from h'perimmuni?ed persons)
, ABA% of RI< given into ite site, and the rest given IB to confer short term protection
)hile )aiting for vaccine to stimulate IR+
, post e"posure proph'la"is )or.s due to long incuaton period
0ontrol of raies
, stra' dog control
, vaccination of dogs
, *uarantine of imported animals
, vaccination of )idlife
DNA NON-ENVELOPED VIRUSES
PARVOVIRUSES
Diseases %arvovirus #1R is the most impt human virus and causes(
, Er'thema infectiosum (slapped chee.s s'ndrome, K
th
disease)
, Aplastic anemia (esp in patients )ith sic.le cell anemia)
, !etal infections, incl+ 1'drops fetalis
Impt properties $er' small (22nm)
Nonenveloped
ss DNA (,)
No virion pol
Icosahedral
Cne serot'pe
Replicative 0'cle Replication in host cell nucleus
ss DNA has hairpin loops at oth ends
, provide ds areas for cellular DNA pol to initiate s'nthesis of progen' genomes
$iral mRNA s'nthesi?ed ' cellular RNA pol frm the ds DNA intermediate
Asseml' in nucleus
- Note( #1R virus replicates onl' )hen a cell is in 4 phase
, )hich e"plains )h' it replicates in red cell precursors ut not in mature cells
8ransmission and
Epidemiolog'
Respirator' route
8ransplacental
#lood
)orld)ide
humans natural reservoir, animals not a source of human infection
%athogenesis and
Immunit'
#1R infects primaril' 2 t'pes of cells(
, er'throlasts in the #B E accounting for aplastic anemia
, endothelial cells in #$ E accounts in part, for rash assoc ) er'thema infectiosum
Immune comple"es of virus and IgB or Ig< can contriute to rash and arthritis in some
people
Immunit' is lifelong
1'drops fetalis manifests as massive edema of the fetus secondar' to 01! ppted '
severe anemia
0linical findings 6 main presentations
1+ Er'thema Infectiosum
,mild disease, 1- of childhood
,right red rash most prominent on chee.s
,lo) grade fever, runn' nose, sore throat
,lac', less intense er'thematous rash on od'
,main complication is arthritis more common in adults, mostl' )omen
2+ Aplastic Anemia
, children ) chronic anemia s+a 40A, thalassemia, can have transient ut severe
aplastic anemia (aplastic crisis)
, normal people do not have clinicall' apparent anemia
5+ !etal infections
, )oman infected ) #1R during 1 or 2 trimester, virus can cross placenta D
infect fetus
, infection in 1
st
trimester leads to death, 2
nd
trimester h'drops fetalis
, third trimester infections do not lead to impt clinical findings
6+ 0hronic #1R infection
, pple )ith immunodeficiencies, esp 1I$, chemotherap', transplant patients can
have chr anemia, leu.openia, or thromoc'topenia as a result of chr #1R
infection
&a Diagnosis 1+ and 2+ usuall' diagnosed ' detecting IgB
#1R isolated frm throat s)as
$iral DNA in lood, %0R
5 detected ' %0R of amniotic fluid
8reatment and
%revention
No specific treatment
%ooled immune gloulins ma' have eneficial effect on chr #1R patients ) Ids
No vaccine
ADENOVIRUSES
Icosahedral DNA virions )ith cuic s'mmetr' and pro=ecting fires
4pecies specific infections of man' animals
0ertain human strains cause malignant tumours in a' hamster (ut not in man)
Diseases Appro! = are asymptomatic, most resolve spontaneously
&ariety of LRF and ERF diseases
, phar'ngitisHR8I )ith fever
, acute follicular con=unctivitis
, pneumonia
, epidemic .eratocon=unctivitis
, hemorrhagic c'stitis(ladder)$ematuria and dysuria prominent,
, gastroenteritis
mesenteric adenitis )ith adominal pain, can mimic appendicitis
intussusception due to abnormal intestinal peristalsis-part of
intestine collapses into itself. Jin-ed blood vessels. 4sc$aemic
necrosis ensues
c$aracterised by non bloody diarr$ea
, chronic infection of tonsils and adenoids
, cervical l'mph adenitis
Important
%roperties
Bnly viruses wit$ a fiber protruding from eac$ of t$e 1( vertices of t$e
capsid Kfiber is a %. organ of attac$ment
61 .no)n Ag t'pes, fiber protein is main type specific Ag
Bost haemagglutinate
All $ave common group specific Ag on $e!on protein
Replicative c'cle Attac$ment via fiber, penetration, uncoating
&iral ;AA moves to nucleus
%ost cell-dependent RAA pol transcribes early genes, splicing
3arly mRAA nonstructural proteins in cytoplasm
After viral ;AA replication in nucleus
- late mRAA transcribed and translated into structural virion proteins
&iral assembly occurs in nucleus
&irus released by cell lysis
8ransmission and
Epidemiolog'
Aerosol
@ecal-oral
;irect inoculation of con9unctiva
certain serotypes are assoc wit$ specific syndromes
- eg #, 2, 5, (1 resp disease
- 8, 1I epidemic -eratocon9unctivitis
- 11 $emorr$agic cystitis
- 20, 21 infantile gastroenteritis
%athogenesis and
Immunit'
Bucosal epi infection of several organsRF, 14F, con9unctiva
4mmunity based on neutrali:ing Ab is type-specific and lifelong
Latent infection, particularly in adenoidal and tonsilar tissues of t$e t$roat
Acute infection -ills cells
8reatment Ao antiviral t$erapy
%revention # live, nonattenuated vaccines against 2,5,(1 used in military
virus infects 14F, causing an asymptomatic infection and induces
immunity to resp. disease
&a diagnosis 8issue culture
, human emr'onic or 1e&a cells
, s)elling and clustering of infected cells )ith IN inclusions (unch of
grapes)
4erolog'
, I! for rapid detection of viral Ag
, 0!8 to adenovirus common group Ag
, 4erot'ping ' N8
RNA NONENVELOPED VIRUSES
PICORNAVIRUSES
&arge famil' of animal viruses characteri?ed ' small si?e (pico), na.ed icosahedral s'mmetr' and ss RNA
(V), 6 ma=or pol'peptides on capsid
8)o genera( rhinoviruses and enteroviruses
#1 RHINOVIRUSES
%roperties Bore than 1:: serot'pes
, neutrali?ing A is serot'pe specific+ 4o )e can have cold 1:: times+
Ba' undergo genetic7Ag variation
Inhaits upp resp tract
0linical
features7
Diseases
0ausative agent of common cold
Incuation 2,6 da's
Rhinorrhoea, snee?ing, sore throat, cough, mild fever (usuall' in children),
hoarseness, headache
lasts 1,2 )ee.s
0omplications (rare)
, sinusitis
, otitis media
, pneumonia
ma' precipitate asthmatic attac.s and aggravate chronic ronchitis
8ransmission 0lose contact
Respirator' secretions
%redominating in rain' seasons
&a
Diagnosis
8issue culture
, unstale elo) p16 (acid,laile)
, optimal gro)th at 55-
, 0%E in human emr'o lung 1 rhinoviruses
, 0%E in mon.e' .idne' cells B rhinoviruses
4erd cot'ping
,N8
8reatment
and 0ontrol
4'mptomatic, no vaccine
#2 ENTEROVIRUSES
4tale
, insensitive to detergents (alcohol, dilute &'sol and lipid solvents)
, survives for months at 6-, survives e"posure to 6:-
Replicates in <I8, prefers )arm, moist environment 9 common in tropics, epidemic in summer mths of
temperate countries
Recentl' reclassified ased on molecular properties+ 1E$ A,D and polioviruses+
%oliovirus 0o"sac.ieviruses Echoviruses
(Enteric 0'topathic
1uman Crphan)
Disease %oliom'elitis a variety of diseases
group A viruses (26 serot'pes)(
, mainl' epithelial infections+
herpangina, acute $emorr$agic
con=unctivitis, 1!B (0A16)
group # viruses )0 serotypes+ (
, mainl' muscular infections+
>leurodynia(#ornholm/s disease),
m'ocarditis, pericarditis,
bot$ groups cause nonspecific
ERF disease, febrile ras$es, aseptic
meningitis, encephalitis
)ide range of
disease spectrum(
aseptic meningitis,
ERF infection,
febrile illness wit$
and wit$out ras$,
infantile diarr$ea,
$emorr$agic
con9unctivitis
O5: serot'pes
Impt
prop
5 serologic (antigenic) t'pes based on
antigenic determinants on t$e outer
capsid proteins
No common Ag
little N-r!n, protection re8uires
presence of Ab against all # types
group classification is ased on
pathogenit' in mice and their
capacit' to gro) in cell cultures
Replica
tive
c'cle
&irion interacts w specific cell R on
cell membrane, t$en enters cell.
Capsid proteins t$en removed
After uncoating, t$e genome RAA
functions as mRAA, translated into one
very large polypeptide called noncapsid
viral protein 00.
Cleaved by virus encoded protease to
As in poliovirus As in poliovirus
form bot$ capsid proteins in progeny
virions as well as several noncapsid
proteins, incl RAA pol to synt$esi:e
progeny RAA genome
"ynt$esis of complementary Kve
strand, w$ic$ serves as template for
?ve strand
"ome of t$ese ?ve strands serve as
templates to ma-e more viral proteins,
ot$ers become viral genome RAA
Assembly by coating genome RAA
wit$ capsid proteins
Release by lysis and deat$ of cell
8ransmi
ssion
and
Epidem
iolog'
!ecal,oral
, replicates in t$e orop$aryn! and
14F
disease ecame impt ) increased
h'giene>
humans are the onl' susceptile hosts
4ntact virus $ost range limited to
primates
- due to binding of viral capsid protein
to a R found only on primate cell
membranes
- $owever, purified RAA can enter and
replicate in many nonprimate cells
)can bypass cell membrane R, ie it is
infectious RAA+
virtually eradicated due to effective
vaccination
, rare cases occur in e!posure
to virulent revertants of
attenuated virus of t$e live
vaccine
, unimmuni:ed people e!posed to
wild type w$ile traveling
gloall' distriuted e"cept in places
)ith vaccination
@ecal-oral,
Resp aerosols
, replicates in orop$rayn! and
14F
$umans are t$e only natural $osts
can infect animals ot$er t$an
primates
worldwide infection, primarily in
summer and fall
@ecal-oral
worldwide
distribution
toget$er wit$
Co!sac-ievirus,
leading cause of
aseptic meningitis
%athoge
nesis
and
immuni
t'
Incuation G,16 da's
after replicating in orophar'n" and
<I8, esp in l'mphoid tissue, viraemia+
In a minorit' of cases, virus ma'
involve the 0N4 follo)ing
dissemination+
can also spread retrograde along
a!ons
in CA",
- preferentially replicates in motor
neurons in ant horn
1rp A viruses $ave a predilection
for s-in and //
1rp , viruses cause diseases in
organs s.a $eart, pleura, pancreas,
liver
bot$ can affect meninges and
motor neurons to cause paralysis
bot$ cause viraemia
type specific 4g1 Ab provides
immunity
As in ot$er
enteroviruses+
, deat$ of neurons, muscle paralysis
- also affects brain stem, leading to
ular poliom'elitis)wit$ resp
paralysis+, but rarely damages
cerebral corte!
immune response of intestinal 4gA and
$umoral 4g1
lifelong immunity
0linical
findings
range of responses (ma=or illness onl'
1,2;) ma=or illness ma' present 2,5
da's follo)ing the minor illness or
)ithout an' preceding minor illness+
, inapparent, as'mptomatic
)i+ Abortive >oliomyelitis )most
common+
mild, febrile illness w $eadac$e,
nausea, vomiting, sore t$roat
usually spontaneous recovery
)ii+ Aonparalytic >oliomyelitis
manifests as aseptic meningitis )
fever, $eadac$e, stiff nec-
usually spontaneous recovery
)iii+ >aralytic >oliomyelitis
flaccid paral'sis
rain stem involvement can lead to
resp paral'sis
painful muscle spasms
motor nerve damage is permanent
but some recovery of muscle fn as
ot$er nerve cells ta-e over
a post polio syndrome t$at occurs
many yrs after acute illness $as been
described
- involving mar-ed deterioration of
residual fn of affected muscles
no permanent carrier state, but virus
e!cretion in feces for several mont$s
1+ 1roup A specific diseases
%erpangina
- fever, sore t$roat, tender
vesicles in orop$aryn!
%@/
- vesicular ras$ on t$e $ands G
feet
- ulcerations in mout$
- mainly in c$ildren
(+ 1roup , specific diseases
>$eurodynia
- fever
- severe pleuritic-type c$est pain
/yocarditis and >ericarditis
- fever
- c$est pain
- signs of congestive failure
- dilated cardiomyopat$y w
global $ypo-inesia of
myocardium is a feared se8uel
Quvenile diabetes due to ,2
#+ ;iseases caused by bot$ groups
aseptic meningitis
mild paresis
transient paralysis
ERF infections
minor febrile infections wit$ or
wit$out ras$
&aorat
or'
Diagno
sis
$irus Isolation
, from throat, stool, 04! '
inoculation of cell cultures
, re*uires molecular techni*ues to
differentiate et)een the )ild t'pe and
vaccine t'pe
, virus produces 0%E, can e identified
' neutrali?ation of 0%E )ith specific
$irus Isolation
, in cell culture of suc.ling mice
, ta.es a fe) da's to )ee.s to gro)
, 4ome co"sac.ie A viruses cannot
e easil' isolated in cell culture+
"erology
- Ab titre
$irus Isolation
, in cell culture
, 0%E in cell
culture
"erology
- of little value
- due to large no. of
antisera
4erolog'
, ver' rarel' used for diagnosis+
Cccasionall' used for immune status
screening for immunocompromised
individuals
, rise in A titer
serotypes and no
common antigen
8reatme
nt and
preventi
on
Ao antiviral t$erapy
"ymptomatic relief and resp support
>$ysiot$erapy
$accine (containing 5 serot'pes)
(i) .illed 9 formalin inactivated (4al.
vaccine, inactivated vaccine, I%$)
(ii) live, attenuated (4ain vaccine, oral
vaccine, C%$), serial passage in
primar' mon.e' .idne' cells
, oth induce humoral A, neutrali?es
virus in viraemic stage
- Note( &ive vaccine preferred
interrupts !,C transmission '
inducing IgA )hile replicating in <I8
easier administration
secondar' vaccination
, disadvantages of the life vaccine are(
reversion of attenuated virus to
virulence, esp t'pe 5
can cause disease in
immunodeficient person
infection of <I8 ' other
enteroviruses can limit replication and
reduce protection
cold chain
, Disadvantages of I%$ are(
confers immunit' ut still acts as a
carrier
, duration of immunit' thought to e
longer ) live than .illed, ut ooster
recommended ) oth
, 3illed vaccine is used in 2 special
instances
initial vaccination of unimmuni?ed
adults (ris. of disease frm live vaccine
higher in adults than in children), then
give dose of live vaccine+ 0irculating
Ao anti-viral t$erapy
Ao vaccine
Ao passive immuni:ation
recommended.
Ao antiviral
t$erapy
no vaccine
As induced ' the 1
st
2 immuni?ations
)ill neutrali?e an' revertants
immunodefecient individuals
, passive immuni?ation )ith
immune serum gloulin
, 4ingapore 4chedule
5, 6 , K months, ooster at 12 mths,
ooster at presch, C%$
C81ER EN8ERC$IRH4E4(
1) E$G:
, main cause of acute hemorrhagic con=unctivitis, ) petechial hemorrhages on ular con=unctivas
, complete recovery usually occurs. Ao t$erapy.
2) E$ G1
, one of the leading causes of viral 0N4 disease, incl+ Beningitis, encephalitis, paral'sis+ Also causes 1!B and
herpangina
&a Diagnosis
, generall', serolog' ver' rarel' used due to P,reactivit'
, molecular methods of R8,%0R and genetic se*uencing used instead+
%revention
, some use I$I<
, efficac' is uncertain
%leconaril
, active against certain enteroviruses
1!BD in 4ingapore
, common, mild childhood infection
, caused ' several different serot'pes of E$, commonl' 0A16, 0A26 and more recentl' E$G1
, in outrea.s in 4ara)a., and 8ai)an, deaths due to encephalitis and neurogenic pulmonar' oedema
, made a legall' notifiale disease in Cct 2::1
, E$ G1
common infection
highest seroconversion rate in children aged 2,K 'rs
seroconversion rate slo)s OK 'rs
neutrali?ing A titre reduces )ith age 9 lo) reinfection rates