ViralViral infectionsinfections ChildhoodChildhood infectionsinfections

fever

fever with a rash

fever with a serious localised infection site of infection

many infections lack • localisation •rash • severe complications ...but these may evolve Plan:Plan:

Exanthems Enteroviruses

„ Measles „ Echo

„ Rubella „ coxsackie „ Mumps Retroviruses „ Parvovirus Parvovirus „ HIV

Herpesviridae „ HTLV „ EBV Miscellaneous „ CMV CMV „ Molluscum „ HHV6 HHV6 „ HPV „ VZV VZV „ adeno „ HSV

measlesmeasles rubellarubella FeverFever erythemaerythema infectiosuminfectiosum withwith aa ((parvoparvo)) blotchyblotchy roseolaroseola infantuminfantum (HHV6)(HHV6) oror spottyspotty scarletscarlet feverfever rashrash erythemaerythema multiformemultiforme KawasakiKawasaki diseasedisease systemicsystemic JCAJCA (Still(Still’’s)s) allergyallergy VirusVirus classificationclassification CommonCommon viralviral pathogenspathogens inin childhoodchildhood (1)(1) DNADNA virusesviruses typical manifestation Pox viruses „ molluscum contagiosum benign skin nodules Herpes viruses „ HSV 1 stomatitis „ HHV 6 roseola infantum „ varicella zoster chickenpox „ cytomegalovirus congenital infection „ Epstein-Barr virus infectious mononucleosis Adenoviruses „ many serotypes URTI Small DNA viruses „ parvovirus erythema infectiosum CommonCommon viralviral pathogenspathogens (2)(2) RNARNA virusesviruses

„ rubeola (measles) ‘childhood fevers’ „ rubella (German measles)

„ mumps

„ rhino

„ respiratory syncytial virus respiratory infection „ influenza

„ parainfluenza

„ rotavirus diarrhoea „ Norovirus

„ coxsackie enteroviruses „ echo

„ polio

„ human immunodeficiency other important viruses virus

„ dengue 7 year old boy • cough • fever • sore eyes

MeaslesMeasles

HighlyHighly contagiouscontagious acuteacute viralviral illnessillness duedue toto aa paramyxovirusparamyxovirus andand characterisecharacterise byby classicclassic triad:triad:

„ CoughCough

„ CoryzaCoryza

„ ConjunctivitisConjunctivitis Measles:Measles: epidemiologyepidemiology

EndemicEndemic worldwideworldwide KillsKills ~1~1 millionmillion eacheach yearyear 22--33 yearlyyearly epidemicsepidemics inin nonnon--vaccinatedvaccinated populationspopulations TemperateTemperate climatesclimates maxmax latelate winterwinter--earlyearly springspring PeakPeak susceptibilitysusceptibility infantsinfants andand yy childrenchildren

„ 40%<16m40%<16m Measles:Measles: aetiologyaetiology

ParamyxovirusParamyxovirus ssRNAssRNA MinorMinor antigenicantigenic shiftsshifts onlyonly seenseen ExternalExternal proteins:proteins:

„ H- haemagglutinin

„ F- fusion

„ Envelope protiens Measles:Measles: pathogenesispathogenesis

Transmission - aerosolised respiratory secretions

„ Max infectivity prodrome to d4 of rash ¾ from 7-10 days after contact

„ Stable for at least 1hr fomites

„ Invades/replicates nasopharynx ¾ →spreads to regional lymphatics ¾ 2o viraemia d5-7 after exposure (esp PBMCs) ¾ Dissem replication d7-14 ¾ Immunity 15-17 d after exposure Measles: incubation Measles: 10 - 14 days commoncommon featuresfeatures 33--44 daysdays ofof URTIURTI--likelike symptomssymptoms ¾fever, coryza, cough ¾conjunctivitis ¾lymphadenopathy ¾Koplik’s spots followedfollowed byby rashrash ¾florid, blotchy ¾starts on head & neck, spreads to whole body Measles:Measles: clinicalclinical picturepicture

Typical:

„ Incubate 8-12d

„ Prodrome ¾ Fever, cough, non-purulent conjuctivitis, coryza

„ Koplik’s spots within 2-3d ¾ Anywhere buccal mucosa

„ Classically opposite lower premolars 12- 72hrs

„ Coalesce

„ Rash ~14 days after exposure ¾ Forehead/post occipital

„ Spreads over 3 days to trunk & extremities

„ Confluent higher up MeaslesMeasles Measles:Measles: exanthematousexanthematous phasephase

highhigh feverfever peakspeaks 22--33 dd afterafter rashrash appearsappears o „ IfIf persistingpersisting thinkthink 22 bacterialbacterial infectioninfection OccasOccas GIGI SxSx-- diarrhoeadiarrhoea majormajor CxCx inin developingdeveloping countriescountries SevereSevere haemorrhagichaemorrhagic measlesmeasles

„ Pneumonia,Pneumonia, seizures,seizures, DIC,DIC, mucosalmucosal bleedsbleeds CanCan getget mildermilder modifiedmodified measlesmeasles postpost exposureexposure ifif givengiven IgIg (longer(longer incubincub)) Measles:Measles: CxCx

11 inin 10001000 ††

„ Usually LRTI (60%) or encephalitis stomatitisstomatitis AOMAOM 77--9%9% LRTILRTI –– viralviral extensionextension oror bacterialbacterial 11--6%6% Developing:Developing: mastoiditis,mastoiditis, pneumonia,pneumonia, diarrhoeadiarrhoea ThrombocytopaeniaThrombocytopaenia,, hepatitis,hepatitis, appendicitisappendicitis etcetc MeaslesMeasles isis aa majormajor causecause ofof childhoodchildhood mortalitymortality inin developingdeveloping countriescountries In some parts of Africa the case fatality rate is as high as 30%.

epithelium devastated

bacterial infection chronic diarrhoea

immunodeficiency malnutrition Measles:Measles: complicationscomplications inin thethe malnourishedmalnourished childchild

stomatitisstomatitis cancrum oris

desquamatingdesquamating rashrash pyoderma

cornealcorneal ulcerationulceration blindness

diarrhoeadiarrhoea malnutrition immunosuppressionimmunosuppression secondary infection MeaslesMeasles encephalitisencephalitis

Acute: 0.1-0.01% 2-6 days after rash starts

„ Mild in most, 15% severe, 25% sequelae Pleocytosis SSPE If wild infection b4 2yo, M>F Sx usually ~10 years after infection Slow behav and intellectual deterioration

„ Then myoclonic seizures, 6-9 months to death EEG: burst suppression MeaslesMeasles MxMx::

VaccineVaccine maymay bebe protectiveprotective ifif withinwithin 7272 hrshrs RespResp isolationisolation untiluntil 55 daysdays afterafter rashrash VitaminVitamin AA

„ DecreasesDecreases diarrhoeadiarrhoea andand pneumoniapneumonia RubellaRubella togavirus,togavirus, ssRNAssRNA OnlyOnly oneone antigenicantigenic typetype respresp transmissiontransmission (n(n--p)p)

„ Day 3-8 after exposure, lasts 11-14 days ActiveActive replicationreplication throughoutthroughout bodybody d8d8--1414 RareRare inin vaccinatedvaccinated populationspopulations

„ Immigrants increased risk incl SEA ImmunityImmunity lifelonglifelong-- AbAb andand CMICMI

„ Reinfection rarely causes cong rubella Rubella:Rubella: incubation 14 - 21 days commoncommon featuresfeatures generallygenerally aa mildmild illnessillness

„ feverfever

„ pinkpink macularmacular rashrash

„ generalisedgeneralised lymphadenopathylymphadenopathy ((suboccipitalsuboccipital nodes)nodes)

„ URTIURTI RubellaRubella complicationscomplications TheseThese areare rarerare inin children:children:

„ thrombocytopaeniathrombocytopaenia

„ encephalitisencephalitis

„ arthritisarthritis

CONGENITAL RUBELLA MainMain risksrisks areare inin firstfirst s deafness s heart defects 33 monthsmonths ofof pregnancy:pregnancy: s mental retardation s cataracts / retinopathy „ abortionabortion s thrombocytopaenia s hepatosplenomegaly „ severesevere birthbirth defectsdefects s bony lesions AcquiredAcquired RubellaRubella

‘‘RashRash andand suboccipitalsuboccipital lymphadenopathylymphadenopathy’’ ProdromeProdrome d10d10--20:20: fever,fever, eyeeye pain,pain, soresore throat,throat, arthralgiaarthralgia RashRash d14d14--21:21: startstart face,face, cephalocaudalcephalocaudal spreadspread overover 24h,24h, fadesfades overover 22--3d3d (m(m--p,p, butbut cancan vary)vary)

„ Can be pruritic in adults AdenopathyAdenopathy-- upup toto 1w1w beforebefore rashrash

„ Suboccipital and post auricular CongenitalCongenital rubellarubella

Risk inversely related to Permanent: gestation ¾ Deafness, pulmonary stenosis, PDA, VSD, „ 80% exposed in TM1 have retinopathy, cataract, defects microphthalmia, UDT, „ Almost none after 16/40 inguinal hernia, IDDM Transient: Delayed: ¾ Thrombocytopaenia, ¾ SNHL, periph PS, MR, hepatosplenomegaly, language defects, IDDM, IUGR, bone lesions immune complex disease,

„ Lymphadenopathy, hypogammaglobulinaemia hepatitis, haemolytic hepatitis, haemolytic „ hypothyroidism anaemia, pneumonitis, cloudy corneas, CongenitalCongenital rubellarubella Ix baby

„ Excretion ¾ceases by 12m in 90% ¾Dx cult from n-p, blood

„ Serol: ¾IgM FPs

„ (Rh factor or maternal IgG) Ix: Maternal

„ EIA IgG,A,M ¾Fourfold rise or single IgM ¾IgM may not be detectable until 1-2w after rash ¾May go 3w after rash ParvovirusParvovirus B19B19

Erythema infectiosum, fifth disease ssDNA, resp droplet spread 50% 2o infection rate in households Single type Erythrocyte P antigen is receptor for virus

„ Also found in myocardium, endothelium, placenta, megakaryocyte, foetal liver Some effects direct, some immune Normal kids:

„ (Direct) Mild fever d8, rash d17-18 ¾ Slapped cheek, spreads extremities lacy reticular

„ (Immune) arthralgia 3w (asymmetrical) ParvovirusParvovirus B19B19 NormalNormal hostshosts Cx:Cx: PregnancyPregnancy

¾HSP, vasculitis „ ~30% foetuses infected ¾Arthropathy „ ~50% women susceptible ¾Neuropathy, meninigitis „ ~6% risk of catching in ¾Transient anaemia, thrombocytopaenia, community outbreak neutropenia „ Death <10%, mainly TM2 HaemoglobinopathyHaemoglobinopathy ¾Spon abortion ¾Pure red cell aplasia ¾Still birth ¾Transient aplastic crisis ¾Non-immune hydrops ImmunosuppressedImmunosuppressed ¾Can affect all haem cell lines HerpesvirusesHerpesviruses

Target cell Latency Transmission

Herpes simplex-1 1 Mucoepithelia Neuron Close contact (HSV-1) Herpes simplex-2 Close contact usually 2 Mucoepithelia Neuron (HSV-2) sexual Varicella Zoster virus Contact or respiratory 3 Mucoepithelia Neuron (VSV) route Epstein-Barr Virus B lymphocyte, 4 B lymphocytes Saliva (EBV) epithelia Monocytes, Contact, blood Cytomegalovirus Epithelia, monocytes, 5 lymphocytes and transfusions, (CMV) lymphocytes possibly others transplantation, congenital Herpes lymphotropic T lymphocytes and T lymphocytes and 6 Contact, respiratory route virus others others Human herpes virus-7 T lymphocytes and T lymphocytes and 7 Unknown (HHV-7) others others Human herpes virus-8 8 Endothelial cells Unknown Exchange of body fluids? (HHV-8) Kaposi's sarcoma- associated 5 year old with fever and rash FeverFever withwith vesiclesvesicles

chickenpox herpes simplex hand, foot and mouth ChickenpoxChickenpox incubation 14 - 16 days commoncommon featuresfeatures moderatemoderate feverfever cropscrops ofof vesiclesvesicles

„ maculemacule >> papulepapule >> vesiclevesicle >> scabscab

„ typicallytypically trunktrunk andand faceface moremore thanthan limbslimbs

„ maymay occuroccur inin mouthmouth

„ sometimessometimes becomebecome bacteriallybacterially infectedinfected Chickenpox:Chickenpox: complicationscomplications In normal children Cx rare (apart from 2o infection)

„ encephalitis (espec. cerebellar ataxia)

„ pneumonia (leaving calcifications on CXR)

„ haemorrhagic form Can be fatal in immunosuppressed patient

„ prophylaxis with zoster immune globuin (ZIG)

„ treatment with intravenous acyclovir Congenital infection

„ risk highest if mother is incubating infection just before or after delivery (transmission rate 25%)

„ give ZIG at birth Shingles in elderly and immunosuppressed Aspirin + VZV = risk factor Reye’s syndrome CMVCMV dsDNAdsDNA herpesherpes virusvirus Latency:Latency: viralviral genomegenome persistspersists asas episomalepisomal PresentPresent allall humanhuman (only)(only) populationspopulations ¾There are non-human CMV species NoNo seasonalseasonal variationvariation EarlyEarly acquisitionacquisition developingdeveloping nationsnations && DCCDCC ¾50-70% children in DCC infected MostMost commoncommon causecause congenitalcongenital infectioninfection CMVCMV transmissiontransmission

DirectDirect oror indirectindirect personperson--toto--personperson contactcontact CloseClose oror intimateintimate contactcontact withwith secretionssecretions CMVCMV transmissiontransmission DirectDirect oror indirectindirect personperson--toto--personperson contactcontact NoNo aerosolaerosol spreadspread CloseClose oror intimateintimate contactcontact withwith secretionssecretions

¾Urine ¾Oropharyngeal secretions ¾Semen ¾Cervicovaginal secretions ¾Tears ¾Breast milk ¾Blood ¾Transplanted organs ExcretionExcretion startsstarts 44--66 wkswks afterafter infectioninfection

„ Persists for months to years

„ Intermittent excretion possible at any time MayMay persistpersist onon fomitesfomites forfor hourshours CMVCMV riskrisk groupsgroups

OccupationalOccupational

„ DCCDCC workersworkers x5x5--1010

„ PaedPaed healthhealth workersworkers nono clearclear increasedincreased riskrisk PerinatalPerinatal CMVCMV

„ PerinatalPerinatal lecturelecture AcquiredAcquired CMV:CMV: normalnormal hosthost

>90%>90% asymptomaticasymptomatic IMIM syndromesyndrome ¾Fever up to 2w ¾Abn LFTs (bilirubin usually N) ¾malaise, HA, atypical lymphocytosis ¾Rash (esp after ampicillin) ¾EBV >CMV UExudative pharyngitis UHepatomegaly USplenomegaly Uadenopathy CMV:CMV: immunocompromisedhostimmunocompromisedhost

FeverFever PolyradiculopathyPolyradiculopathy MalaiseMalaise GraftGraft functionfunction LeukopeniaLeukopenia deteriorationdeterioration TransaminitisTransaminitis PneumonitisPneumonitis PrimaryPrimary ¾4-12 w after Tx RetinitisRetinitis ReactivationReactivation EnterocolitisEnterocolitis EncephalitisEncephalitis CMVCMV DxDx

ViralViral detectiondetection

„ TissueTissue cultureculture

„ AntigenaemiaAntigenaemia detectiondetection (pp65(pp65 andand others)*others)*

„ DNADNA PCRPCR-- quantitative*quantitative* vsvs qualitativequalitative

„ HistologyHistology SerologySerology

„ IgGIgG

„ IgMIgM ¾(FPs in Rh factor, FNs in immunosuppressed) CMVCMV MxMx

TreatmentTreatment

„ Ganciclovir (IV/o)

„ Foscarnet

„ Cidofovir

„ Hyperimmune globulin PreventionPrevention

„ Hyperimmune globulin

„ GCV

„ Hygeine

„ Donor screening

„ Reduce viable leukocytes in blood product EBVEBV dsDNAdsDNA,, herpervirusherpervirus LyticLytic infectioninfection inin oropharyngealoropharyngeal && salivarysalivary cellscells LatentLatent infectioninfection inin BB lymphocyteslymphocytes AllAll humanhuman populationspopulations NoNo seasonalseasonal variationvariation EarlyEarly acquisitionacquisition developingdeveloping worldworld andand ?DCC?DCC AdolescentAdolescent seroprevalenceseroprevalence 4040--50%50% EBVEBV pathogenesispathogenesis

BB cellscells

„ UpUp toto 20%20% infectedinfected

„ MonoclonalMonoclonal andand polyclonalpolyclonal proliferationproliferation

„ ImmortalisationImmortalisation ofof BB cellscells AtypicalAtypical LCsLCs areare cytotoxiccytotoxic CD8CD8 positivepositive

„ KillKill infectedinfected BB cellscells

„ OutnumberOutnumber BB cellscells 50:150:1 EBVEBV transmissiontransmission

OropharyngealOropharyngeal secretionssecretions

„ LowLow titretitre eveneven duringduring acuteacute illnessillness

„ NoNo isolationisolation neededneeded inin hosphosp BloodBlood productsproducts

„ LessLess commoncommon thanthan CMVCMV Clinical:Clinical: acuteacute EBVEBV

AsymptomaticAsymptomatic frequencyfrequency inverseinverse toto ageage IMIM syndromesyndrome NeurologicNeurologic ¾Nerve palsy ¾GBS ¾Meningoencephalitis ¾Transverse myelitis ITPITP MononucleosisMononucleosis syndromesyndrome

IncubationIncubation 3030--50d50d PneumonitisPneumonitis FeverFever NeurolNeurol LymphadenopathyLymphadenopathy MyocarditisMyocarditis Pharyngitis Pharyngitis ThrombocytopaeniaThrombocytopaenia SplenomegalySplenomegaly AnaemiaAnaemia HepatitisHepatitis –– mildmild „ Haemolytic RashRash „ Aplasia „ 15% if no antibiotics neutropenianeutropenia „ 60-80% if beta- lactams EBV:EBV: immunosuppressedimmunosuppressed

XX--linkedlinked lymphoproliferativelymphoproliferative syndromesyndrome PostPost TxTx BB cellcell lymphoproliferativelymphoproliferative syndromesyndrome HIVHIV associatedassociated

„ LymphomaLymphoma

„ OralOral HairyHairy leukoplakialeukoplakia EBVEBV cancerscancers

BurkittBurkitt lymphomalymphoma-- mainlymainly AfricanAfrican typetype NasopharyngealNasopharyngeal carcinomacarcinoma HodgkinHodgkin’’ss (some)(some) EBVEBV DxDx FBE:FBE: plateletsplatelets (low),(low), WCCWCC (up(up oror down)down)

„ film:film: atypicalatypical LCLC HeterophileHeterophile AbAb (Paul(Paul BunnelBunnel)) ¾aggl of sheep/horse RBCs after absorption with guinea pig kidney cells ¾rapid test horse or beef RBCs ¾positivity increases

„ with age (rare<5y)

„ time after Sx onset) serologyserology IgGIgG/M/M VCAVCA

„ alsoalso EBNAEBNA (6(6--12w)12w) // EAEA HHV6HHV6

RoseolaRoseola infantuminfantum::

„ virusvirus 1st1st notednoted inin LCLC ofof infantinfant 19881988 infectsinfects TT lymphocytes,lymphocytes, espesp activatedactivated CD4CD4 ?latency?latency inin macrophagesmacrophages 22 types:types:

„ AA-- adultsadults-- ?role?role

„ BB-- roseolaroseola andand otherother febrilefebrile illnessesillnesses HHV6HHV6

Worldwide,Worldwide, nono seasonalseasonal variationvariation peakpeak 66--1212 monthsmonths ofof ageage 66--12m:12m: causescauses 20%20% allall EDED visitsvisits

„ 9.7%9.7% allall EDED visitsvisits <3<3 yearsyears mostmost adultsadults sero+vesero+ve shedshed intermittently,intermittently, oftenoften asymptomaticasymptomatic

„ virusvirus presentpresent inin salivasaliva ofof healthyhealthy adultsadults ¾?major source transplacentaltransplacental possible,possible, BMilkBMilk ?not?not fdfd HHV6HHV6 clinicallyclinically

ImmunosuppressedImmunosuppressed

„ BMBM suppressionsuppression inin BMTBMT && HIVHIV

„ interstitialinterstitial pneumonitispneumonitis

„ renalrenal dysfunctiondysfunction

„ skinskin rashrash neurologicalneurological manifestationsmanifestations ¾aseptic meiningitis ¾FCs ¾meningoencephalitis ¾?MS flares HHV6HHV6 clinicallyclinically

HighHigh feverfever 33--55 daysdays InflamedInflamed TMsTMs „ ‘no focus’ often URIURI SxSx irritableirritable GIGI SxSx adenopathyadenopathy:: Cx/occCx/occ bulgingbulging AFAF rashrash-- macmac--pappap FebrileFebrile seizuresseizures

„ „ 25% during fever „ 15-20%

„ „ most after fever „ incl recurrent FCs „ Nagayama’s spots ¾red papules buccal mucosa HHV6HHV6

DxDx::

„ SerologySerology

„ PCRPCR ¾+ve indicates current or past infection ¾plasma rather than whole blood indicates active Rx:Rx:

„ inin vitrovitro susceptiblesusceptible toto GCV,GCV, foscarnetfoscarnet,, cidofovircidofovir HHV7HHV7

FrequentFrequent olderolder thanthan HHV6HHV6 mildmild fever,fever, rashrash etcetc foundfound inin breastbreast milkmilk andand adultadult salivasaliva HHV8HHV8

KaposiKaposi’’ss sarcomasarcoma

„ doesdoes occuroccur inin childhoodchildhood inin AfricaAfrica ?transmission?transmission HSV:HSV:

LatencyLatency inin neuronneuron DRGDRG episomeepisome

„ nono rolerole inin malignancy/transformationmalignancy/transformation neurovirulentneurovirulent HSVHSV thymidinethymidine kinasekinase

„ VZVVZV has,has, CMVCMV doesdoes notnot cancan affectaffect anyany organorgan ofof bodybody worseworse ifif TT cellcell abnormalityabnormality ??AbAb onlyonly importantimportant forfor neonatesneonates HSVHSV RxRx

ValacyclovirValacyclovir prodrugprodrug forfor ACVACV FamcyclovirFamcyclovir alsoalso actsacts TKTK FoscarnetFoscarnet reservedreserved forfor resistantresistant virusvirus

„ ActsActs onon viralviral DNADNA polymerasepolymerase VerticallyVertically acquiredacquired HIVHIV-- NHxNHx

20%20% earlyearly progressionprogression toto AIDSAIDS andand deathdeath inin infancyinfancy 4040--50%50% survivedsurvived toto 1010 yearsyears withoutwithout ARTART Scenario:Scenario: HIVHIV ++veve mothermother

YouYou areare calledcalled toto counselcounsel anan HIVHIV positivepositive mothermother aboutabout verticalvertical transmisiontransmision ofof HIVHIV WhatWhat isis thethe transmissiontransmission risk?risk? WhatWhat areare thethe riskrisk factors?factors? WhatWhat interventionsinterventions maymay reducereduce risk?risk? HowHow willwill youyou managemanage andand diagnosediagnose thethe baby?baby? HIV:HIV: kidskids aintaint adultsadults

VLVL muchmuch higher,higher, espesp earlyearly CD4CD4 countscounts ageage dependentdependent

„ MuchMuch higherhigher inin infancyinfancy

„ UseUse CD4%CD4% LifetimeLifetime ofof RxRx

„ Resistance/optionsResistance/options

„ ToxicityToxicity VerticalVertical Transmission:Transmission:

AccountsAccounts forfor >90%>90% paediatricpaediatric HIVHIV

„ RiskRisk ifif HIVHIV positivepositive mothermother ¾Europe ~14%, Africa ~30% InIn uteroutero -- fromfrom 11st trimestertrimester IntrapartumIntrapartum –– 5050--70%70% vertvert tt’’missionmission

„ ContactContact withwith infectedinfected secretionsecretion oror bloodblood PostpartumPostpartum –– 1414--29%*29%*

„ BreastfeedingBreastfeeding RiskRisk factorsfactors forfor verticalvertical infectinfectnn::

AdvancedAdvanced maternalmaternal disease/lowdisease/low CD4CD4 HighHigh viralviral loadload NVDNVD ((vsvs LUSLUSCCS)S) ROMROM >> 44 hourshours BloodyBloody deliverydelivery prematurityprematurity BreastBreast feedingfeeding-- espesp longlong termterm WhatWhat cancan wewe do?do? AntenatallyAntenatally:: MaximiseMaximise maternalmaternal statusstatus

„ Health,Health, nutritionnutrition DiminishDiminish viralviral load,load, raiseraise CD4CD4 %%

„ MaximiseMaximise antianti--retroviralretroviral regimenregimen byby deliverydelivery BookBook forfor electiveelective LUSCSLUSCS atat 37/4037/40 DonDon’’tt breastbreast feedfeed VerticalVertical TransmissionTransmission-- AntiretroviralAntiretroviral treatment:treatment: ACTGACTG 076076

„ MaternalMaternal zidovudinezidovudine (ZDV)(ZDV) popo fromfrom 34/4034/40

„ ZDVZDV IVIV duringduring labourlabour st „ OralOral ZDVZDV toto infantinfant forfor 11 66 weeksweeks

„ ReducedReduced riskrisk fromfrom 25.5%25.5% toto 8.3%8.3% VerticalVertical TransmissionTransmission-- AntiretroviralAntiretroviral treatment:treatment: HIVNETHIVNET 001122 OralOral nevirapinenevirapine (NVP)(NVP) singlesingle dosesdoses ¾to mother at onset of labour ¾to baby at 48 hours vsvs modifiedmodified 076076 protocolprotocol NearlyNearly allall breastbreast fed,fed, RVRV atat 1414--1616 ww Transmission:Transmission:

„ NVPNVP 13.1%,13.1%, ZDVZDV 25.1%25.1% CostCost--effectiveeffective VerticalVertical TransmissionTransmission-- managementmanagement ofof newborn:newborn: DiagnosticDiagnostic PCR:PCR: st „ 11 atat 4848 hrshrs pickpick upup 38%38% nd „ 22 atat 22--44 weeksweeks pickpick upup 93%93% ¾IF NEGATIVE HERE:

„ CEASE ANTIRETROVIRALS

„ START SEPTRIN rd „ 33 atat 44 monthsmonths pickpick upup 99.7%99.7% ¾IF NEGATIVE HERE:

„ CEASE SEPTRIN th „ 44 atat 6m6m serologyserology atat 12,12, 1818 monthsmonths VerticalVertical TransmissionTransmission-- drugdrug managementmanagement ofof newborn:newborn: UsuallyUsually mothermother onon HAARTHAART IntrapartumIntrapartum ZDVZDV NeonatalNeonatal ZDVZDV

„ +/+/-- 3TC3TC

„ andand NVPNVP (intrapartum(intrapartum andand neonatal)neonatal)

„ andand bothboth

„ forfor 44--66 weeksweeks possiblepossible maternalmaternal viralviral resistanceresistance

HIVHIV testingtesting

Serology: screen with ELISA, confirm with Western blot. OK after 18months, when maternal Ab waned. HIV DNA PCR: Preferred test to diagnose HIV infection in infants and children younger than 18 months of age; highly sensitive and specific by 2 weeks of age and available; performed on peripheral blood mononuclear cells HIV p24 Ag: Less sensitive, false-positive results during first month of life, variable results; not recommended ICD p24 Ag: Commonly available; negative test result does not rule out infection; not recommended HIV culture: Expensive, not easily available, requires up to 4 wk to do test HIV RNA PCR: Not recommended for routine testing of infants and children younger than 18 months of age because a negative result cannot be used to exclude HIV infection AreAre therethere risksrisks ofof therapy?therapy?

?lactic?lactic acidosis/mitochondrialacidosis/mitochondrial defectsdefects

„ relativerelative potencypotency inhibitinginhibiting mitochondrialmitochondrial gammagamma DNADNA polymerasepolymerase highesthighest for:for: ¾ddC, followed by didanosine (ddI), stavudine (d4T), 3TC, ZDV and abacavir (ABC)

„ KeepKeep watchingwatching thisthis spacespace

„ Adults/olderAdults/older childrenchildren lipodystrophylipodystrophy syndsynd ?preterm?preterm-- notnot clearclear associationassociation

„ RaisedRaised forfor combinationcombination therapytherapy HIV:HIV: toto treattreat oror not?not?

InfantsInfants AlwaysAlways startstart if:if: ¾Stage C ¾CD4<20% ¾CD4 rapidly falling and persistent high VL>106/ml ConsiderConsider inin anyany infectedinfected infantinfant HIV:HIV: toto treattreat oror not?not?

ChildrenChildren >12m>12m AlwaysAlways startstart if:if: ¾CD4%<15 ConsiderConsider if:if: ¾Stage B ¾CD4%<20 or VL>105 DeferDefer if:if: ¾Stage N or A ¾CD4%>20 ¾VL<105 HIVHIV therapiestherapies kidskids cancan taketake

NRTIsNRTIs

„ ZDVZDV,, ddIddI,, ddCddC,, d4T,d4T, 3TC3TC,, ABCABC NNRTIsNNRTIs

„ NevirapineNevirapine NVPNVP,, efavirenzefavirenz EFVEFV,, delvaridinedelvaridine DLVDLV PIsPIs

„ IndinavirIndinavir,, ritonavirritonavir,, saquinavirsaquinavir,, nelfinavirnelfinavir,, amprenaviramprenavir,, lopinivir/ritonavirlopinivir/ritonavir TopicalTopical virusesviruses

EnterovirusEnterovirus 7171

„ HFM,HFM, neurologicalneurological andand systemicsystemic diseasedisease

„ SEASEA NipahNipah virusvirus MalaysiaMalaysia 19981998

„ flyingflying foxesfoxes naturalnatural hosthost SARSSARS

„ coronaviruscoronavirus EnterovirusesEnteroviruses

SmallSmall RNARNA virusesviruses ((PicornavirusesPicornaviruses)) ssRNAssRNA RapidRapid replicationreplication inin hosthost cell=>cell=> cellcell lysislysis Groups:Groups:

„ A1A1--2424

„ B1B1--66

„ EchovirusesEchoviruses (31)(31)

„ EnterovirusesEnteroviruses (types(types 6868--71)71)

„ PoliovirusesPolioviruses (types(types 11--3)3) EnterovirusEnterovirus disease:disease: distinctdistinct viruses,viruses, diversediverse arrayarray diseasedisease SummerSummer peakpeak timetime HumansHumans onlyonly naturalnatural hosthost FaecoFaeco--oral,oral, respresp,, mothermother--infantinfant tmissiontmission

„ FaecalFaecal sheddingshedding ~8w~8w

„ RespResp sheddingshedding ~1w~1w FomiteFomite spreadspread possiblepossible IncubIncub 33--6d6d EnterovirusEnterovirus manifestations:manifestations:

„ DifferentDifferent tissuetissue tropismstropisms ¾Non-spec febrile illness ¾Resp: URTI….pneumonia ¾CNS disease: aseptic meningitis, encephalitis, paralysis ¾Skin exanthem/enanthem: HFM

„ A16, Echo19, EV71 ¾Eye: acute haemorrhagic conjunctivitis ¾Cardiac: myocarditis, pericarditis

„ Coxsackie B1-5 ¾GI: V, D, abdominal pain, hepatitis EVEV meningitismeningitis cancan bebe neutrophilianeutrophilia inin CSFCSF earlyearly ManyMany differentdifferent serotypesserotypes possiblepossible MostMost inin childhoodchildhood NotNot associatedassociated withwith permanentpermanent sequelaesequelae DailyDaily PCRPCR costcost--effectiveeffective inin USUS studiesstudies pleconarilpleconaril EVEV DxDx::

Culture:Culture:

„ Throat,Throat, faeces,faeces, rectalrectal swab,swab, blood,blood, BxBx

„ PositivePositive cultureculture fromfrom anywhereanywhere exceptexcept faecesfaeces diagnosticdiagnostic PCRPCR

„ ?Gold?Gold standardstandard SerologySerology

„ PolioPolio mainlymainly