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VIRAL INFECTIONSVIRAL INFECTIONS

Dr Tom Connell

Infectious Disease Physician

PLANPLANQuizClassification of viruses

Cases and descriptions

Viruses and pregnancyViruses and pregnancy

Prevention

Common and not so common viruses in

children

‘Virus’ is a latin word used by doctors to mean “your guess is as good as mine”

QUIZQUIZ

1. Which of the following viruses has not been 1. Which of the following viruses has not been associated with malignancy?associated with malignancy?

CMVEBVHHV 8HHV-8HIVHPV

2. 2. 2 yr old. Lesions on 2 yr old. Lesions on hands and feethands and feet

Fever 38 CFever 38 C

Coxackie A16EBVHSV-1HHV-6Parvovirus B19

3. Day 3 MRI, HSM, Purpuric rash3. Day 3 MRI, HSM, Purpuric rashMicrocephalyMicrocephalyWhat is the most likely What is the most likely diagnosis?diagnosis?

CMVHSVHSVRubellaSyphilisToxoplasmosis

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4. In developed countries, breast feeding is 4. In developed countries, breast feeding is contraindicated by which of the following maternal contraindicated by which of the following maternal

infections?infections?

CMVHepatitis AHepatitis BHepatitis BHepatitis CHIV

5. Human metapneumovirus is most commonly 5. Human metapneumovirus is most commonly associated with which of the following?associated with which of the following?

BronchiolitisCroupFebrile convulsionFebrile convulsionGastroenteritisViral exanthem

6. Which of these signs is not associated with 6. Which of these signs is not associated with congenital CMV?congenital CMV?

AnaemiaCataractChorioretinitisChorioretinitisHepatosplenomegalyIUGR

7. Term infant. Mum Hep B +. What is the most 7. Term infant. Mum Hep B +. What is the most appropriate management of infant?appropriate management of infant?

Hep B vaccineHep B vaccine and immunoglobulinCheck LFTs Check LFTs Withhold hepatitis B vaccineExclusion of breats milk

8. 7 year old finished intensive chemo. WBC 8. 7 year old finished intensive chemo. WBC 1.1 In contact with VZV. What is the most 1.1 In contact with VZV. What is the most

appropriate management?appropriate management?

VZIGIV aciclovirIntragamOral ACVVaricella vaccine

9. Which one of the following virus families is 9. Which one of the following virus families is are not RNA viruses?are not RNA viruses?

HepadnaParomyxovirusCoronovirusCoronovirusFlavivirusTogavirus

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10. Which of the following statements 10. Which of the following statements concerning Parvovirus B 19 is concerning Parvovirus B 19 is NOTNOT true?true?

DNA virusIncubation period 4-16 daysAlso called fifth diseaseAlso called fifth diseaseMainly affects young childrenThe majority of infections are

asymptomatic

11. Which of the following conditions has not 11. Which of the following conditions has not been associated with parvoviral infection?been associated with parvoviral infection?

GlomerulonephritisParotitisChronic fatigue syndromeChronic fatigue syndromeMeningitisPurpuric rash

12. Which one of the following statements 12. Which one of the following statements concerning parvovirus in pregnancy is true?concerning parvovirus in pregnancy is true?

Risk highest in the first trimesterIntruterine death is commonLong term effects are commong1:1000 during pregnancyIgG+/Igm- maternal serology indicates

immunity

13. Which one of the following 13. Which one of the following statements is true in relation to HHVstatements is true in relation to HHV--6? 6?

Causes fifth diseaseMost children acquire infection by age 2

yearsyearsAlso called exanthem subitumSeroprevalence is lowHigh mortality

14. Which one of the following conditions is 14. Which one of the following conditions is NOTNOT associated with congenital rubella?associated with congenital rubella?

ChorioretinitisIUGRDeafnessDeafnessPDAThrombocytopenia

15. In a measles outbreak/contact, which of 15. In a measles outbreak/contact, which of the following measures is most appropriate?the following measures is most appropriate?

Infants age 9-12 months should be give one MMR vaccine that will cover for the 12 month immunisation

Measles immunoglobulin should be Measles immunoglobulin should be administered to all contacts

Exclude from school for 7 daysMMR vaccine should be given to susceptible if

within 72 hours

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16. Which of the following statements is 16. Which of the following statements is true concerning swine flu influenza?true concerning swine flu influenza?

High mortality in general populationVaccine associated with high risk of GBSInfluenza B virusInfluenza B virusOseltamavir is contraindicated in

pregnancyIncubation period 3-5 days

17. Which of the following statements is NOT 17. Which of the following statements is NOT true in relation to HIV infection?true in relation to HIV infection?

Untreated the chance of MTCT is 30%CMV is not an AIDS defining illnessInfected infants < 12 months should be Infected infants 12 months should be

treated based on VL and CD4 countHIV-infected mothers should not

breastfeedWith treatment in pregnancy rates of

transmission < 1%

18. 3 year old John was found by his mum with a syringe in his 18. 3 year old John was found by his mum with a syringe in his hand. He was crying and it appeared that there was a small hand. He was crying and it appeared that there was a small puncture wound to his hand. Which of the following is true puncture wound to his hand. Which of the following is true

concerning his risk of viral infection with Hep B, Hep C and HIV if concerning his risk of viral infection with Hep B, Hep C and HIV if there had been a significant exposure?there had been a significant exposure?

HIV 10%, Hep B 3%, Hep C, 30%, HIV 0.3%, Hep B 30%, Hep C 3%, p , pHIV 30%, Hep B 3%, Hep C 0.3%HIV 0.1%. Hep B 1%, Hep C 10%

19. Which of the following medications is most 19. Which of the following medications is most likely to be used to treat Hepatitis B infection?likely to be used to treat Hepatitis B infection?

AcyclovirGanciclovirLamivudineLamivudineInterferon gammaVidarabine

20. Which of these situations concerning 20. Which of these situations concerning maternal HSV is associated with the greatest maternal HSV is associated with the greatest

risk to the baby?risk to the baby?

Mother has recurrent genital HSV-infection

Mother acquires infection with HSV-2 Mother acquires infection with HSV 2 having had HSV-1 (non-primary)

Mother has primary HSV-1 early in pregnancy

Mother has primary HSV-1 at 34 weeks

21. Which is 21. Which is notnot a category of antia category of anti--retroviral retroviral medications?medications?

Nucleoside reverse transcriptase inhibitors

Non-nucleoside reverse transcriptase Non nucleoside reverse transcriptase inhibitors

Fusion inhibitorsCCR4 antagonists

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22. WHO recommends treating which of the 22. WHO recommends treating which of the following with HIV?following with HIV?

All infants less than 1 yr of ageOnly infants with CD4% <25Only infants with VL>100 000Only infants with VL>100,000No infants as they are at less risk

23. Which strain was responsible for the 23. Which strain was responsible for the swine flu pandemic?swine flu pandemic?

H3N2H5N1H1NIH1NIH2N3

24. Estimated number of confirmed 24. Estimated number of confirmed cases of swine flu in Australia in 2009?cases of swine flu in Australia in 2009?

404004000400040000

25. Estimated number of deaths due to swine 25. Estimated number of deaths due to swine flu in Australia in 2009flu in Australia in 2009

202002000200020000

1. Which of the following viruses has not been 1. Which of the following viruses has not been associated with malignancy?associated with malignancy?

CMVEBVHHV 8HHV-8HIVHPV

2 yr old. Lesions on hands 2 yr old. Lesions on hands and feetand feet

Fever 38 CFever 38 C

Coxackie A16EBVHSV-1HHV-6Parvovirus B19

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3.3. Day 3 MRI, HSM, Day 3 MRI, HSM, Purpuric rash, Purpuric rash, MicrocephalyMicrocephalyWhat is the most likely What is the most likely diagnosis?diagnosis?

CMVHSVHSVRubellaSyphilisToxoplasmosis

4. In developed countries, breast feeding is 4. In developed countries, breast feeding is contraindicated by which of the following maternal contraindicated by which of the following maternal

infections?infections?

CMVHepatitis AHepatitis BHepatitis BHepatitis CHIV

5. Human metapneumovirus is most commonly 5. Human metapneumovirus is most commonly associated with which of the following?associated with which of the following?

BronchiolitisCroupFebrile convulsionFebrile convulsionGastroenteritisViral exanthem

6. Which of these signs is not associated with 6. Which of these signs is not associated with congenital CMV?congenital CMV?

AnaemiaCataractChorioretinitisChorioretinitisHepatosplenomegalyIUGR

7. Term infant. Mum Hep B and C +. What is 7. Term infant. Mum Hep B and C +. What is the most appropriate management of infant? the most appropriate management of infant?

Hep B vaccineHep B vaccine and immunoglobulinCheck LFTs Check LFTs Withhold hepatitis B vaccineExclusion of breats milk

8. 7 8. 7 --year old finished intensive chemo. WBC year old finished intensive chemo. WBC 1.1 In contact with VZV. What is the most 1.1 In contact with VZV. What is the most

appropriate management?appropriate management?

VZIGIV aciclovirIntragamIntragamOral ACVVaricella vaccine

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9. Which one of the following virus families is 9. Which one of the following virus families is not an RNA virus?not an RNA virus?

HepadnaParomyxovirusCoronovirusCoronovirusFlavivirusTogavirus

10. Which of the following statements 10. Which of the following statements concerning Parvovirus B 19 is concerning Parvovirus B 19 is NOTNOT true?true?

DNA virusIncubation period 4-16 daysAlso called fifth diseaseAlso called fifth diseaseMainly affects young childrenThe majority of infections are

asymptomatic

11. Which of the following conditions has been 11. Which of the following conditions has been not been associated with parvoviral infection?not been associated with parvoviral infection?

GlomerulonephritisParotitisChronic fatigue syndromeChronic fatigue syndromeMeningitisPurpuric rash

12. Which one of the following statements 12. Which one of the following statements concerning parvovirus in pregnancy is trueconcerning parvovirus in pregnancy is true

Risk highest in the first trimesterIntrauterine death is commonLong term effects are commong1:1000 during pregnancyIgG+/IgM- maternal serology indicates

immunity

13. Which one of the following 13. Which one of the following statements is true in relation to HHVstatements is true in relation to HHV--6?6?

Causes fifth diseaseMost children acquire infection by age 2

yearsyearsAlso called exanthem subitumSeroprevalence is lowHigh mortality

14. Which one of the following conditions is 14. Which one of the following conditions is NOTNOT associated with congenital rubella? associated with congenital rubella?

ChorioretinitisIUGRDeafnessDeafnessPDAThrombocytopenia

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15. In a measles outbreak/contact, which of 15. In a measles outbreak/contact, which of the following measures is most appropriate?the following measures is most appropriate?

Infants age 9-12 months should be give one MMR vaccine that will cover for the 12 month immunisation

Measles immunoglobulin should be administered to all Measles immunoglobulin should be administered to all contacts

Exclude from school for 7 daysMMR vaccine should be given to susceptible if within

72 hours

16. Which of the following statements is 16. Which of the following statements is true concerning swine flu influenza?true concerning swine flu influenza?

High mortality in general populationVaccine associated with high risk of GBSInfluenza B virusInfluenza B virusOseltamavir is contraindicated in

pregnancyIncubation period 3-5 days

17. Which of the following statements is 17. Which of the following statements is NOTNOTtrue in relation to HIV infection?true in relation to HIV infection?

Untreated the chance of MTCT is 30%CMV is not an AIDS defining illnessInfected infants < 12 months should be Infected infants 12 months should be

treated based on VL and CD4 countHIV-infected mothers should not

breastfeedWith treatment in pregnancy rates of

transmission < 1%

18. 3 year old John was found by his mum with a syringe in his 18. 3 year old John was found by his mum with a syringe in his hand. He was crying and it appeared that there was a small hand. He was crying and it appeared that there was a small puncture wound to his hand. Which of the following is true puncture wound to his hand. Which of the following is true

concerning his risk of viral infection with Hep B, Hep C and HIV if concerning his risk of viral infection with Hep B, Hep C and HIV if there had been a significant exposure?there had been a significant exposure?

HIV 10%, Hep B 3%, Hep C, 30%, HIV 0.3%, Hep B 30%, Hep C 3%, p , pHIV 30%, Hep B 3%, Hep C 0.3%HIV 0.1%. Hep B 1%, Hep C 10%

19. Which of the following medications is most 19. Which of the following medications is most likely top be used to treat Hepatitis B likely top be used to treat Hepatitis B

infection?infection?

AcyclovirGanciclovirLamivudineLamivudineInterferon gammaVidarabine

20. Which of these situations concerning 20. Which of these situations concerning maternal HSV is associated with the greatest maternal HSV is associated with the greatest

risk to the baby?risk to the baby?

Mother has recurrent genital HSV-infection

Mother acquires infection with HSV-2 Mother acquires infection with HSV 2 having had HSV-1 (non-primary)

Mother has primary HSV-1 early in pregnancy

Mother has primary HSV-1 at 34 weeks

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21. Which is 21. Which is notnot a category of antia category of anti--retroviral retroviral medications?medications?

Nucleoside reverse transcriptase inhibitors

Non-nucleoside reverse transcriptase Non nucleoside reverse transcriptase inhibitors

Fusion inhibitorsCXCR4 antagonists

22. WHO recommends treating which of the 22. WHO recommends treating which of the following with HIV?following with HIV?

All infants less than 1 yr of ageOnly infants with CD4% <25Only infants with VL>100 000Only infants with VL>100,000No infants as they are at less risk

23. Which strain was responsible for the 23. Which strain was responsible for the swine flu pandemic?swine flu pandemic?

H3N2H5N1H1NIH1NIH2N3

24. Estimated number of confirmed 24. Estimated number of confirmed cases of swine flu in Australia in 2009?cases of swine flu in Australia in 2009?

404004000400040000

25. Estimated number of deaths due to swine 25. Estimated number of deaths due to swine flu in Australia in 2009flu in Australia in 2009

202002000200020000

Classification of virusesClassification of viruses

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Classification of VirusesClassification of Viruses Classification of VirusesClassification of VirusesHerpesHHV 6EBVCMVMolluscumHPVAdenovirusParvovirus

RubeolaRubella

Parvovirus RhinovirusInfluenzaParainfluenzaRotavirusEnterovirusCoxsackieHIV

FEVER WITH RASHFEVER WITH RASH

CASE 1 StephanieCASE 1 Stephanie

Febrile ~ 1 week ago

Rash

Rash over trunk and extremitiesRash over trunk and extremities

Pale

CluesClues

DNA virus

This disease is also a numberThis disease is also a number

Also called slapped cheek

And the answer ……..

PARVOVIRUS B19PARVOVIRUS B19Erythema infectiosum (Stricker 1899)Fifth diseaseDNA virus1st known human parvovirus (discovered in

petri dish B19)petri dish B19)Grows only in dividing cellsSpread - direct contact with secretions (group

of volunteers infected nasally with B19)Can be transmitted by blood transfusionIncubation period 4-15 days

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PARVOVIRUS B19PARVOVIRUS B19Epidemic pattern similar to RubellaMost prevalent in winter and springVirus shedding between D 5 and D 12Attack rate highest in children 5 to 14 yrsS iti (I G)Seropositive (IgG)

2 to 21% of children < 11yrs40 to 60% adults

Pathophysiology and pathology– Direct effects (lysis)– Indirect (immune)

PARVOVIRUS B19PARVOVIRUS B19

IgM

Non specific fever

Virus excretion

Erythema infectiousum

0 7 14 21 28

Viraemia

Reticulocytes

B19 inhibits the formation of blast forming erythroid colonies

PARVOVIRUS B19 CLINICALPARVOVIRUS B19 CLINICAL

Spectrum20% asymptomaticUsual erythema infectiosumUsual erythema infectiosumUnusual clinical manifestations

Erythema InfectiosumErythema Infectiosum

Prodromal phase 2-3 days (viraemia)Symptom free for 7 daysD18- “slapped cheek”Facial exanthem worsens on going from

d outdoors to warm roomD 19-23 maculopapular rash on trunkHeadache in 20%Arthralgia (80% adults, <10% children)Knees, ankles, PIPJ, bilateralNo isolation

PARVOVIRUS RARE CLINICALPARVOVIRUS RARE CLINICALArthritis (association between B19

and RA)Neurological

– Encephalitis (B19 DNA CSF)– Meningitis– GB syndrome– Facial palsy– CT syndrome

Myocarditis (5 children and 4

• Other– GN– Kawasaki– Behcet– PAN– Wegener’s– HepatitisMyocarditis (5 children and 4

adults)Cutaneous

– EM– HSP– Petechiae

Haematological– TTP– Pancytopenia– Haemophagocytic– DB anaemia

– Hepatitis– SLE– Raynaud– Parotitis– Hepatitis– Pseudoappendicitis– CFS– Chronic haemolytic

anaemia

Stephanie comes back…..Stephanie comes back…..

Rash has gone…

But she is very pale…

WHY??

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PARVOVIRUS B19PARVOVIRUS B19

IgM

Non specific fever

Virus excretion

Aplastic crisis

Erythema infectiousum

0 7 14 21 28

Viraemia

Reticulocytes

B19 inhibits the formation of blast forming erythroid colonies

APLASTIC CRISISAPLASTIC CRISIS

ReticulocytopeniaDecreased RCC lifespanSCA, HS, PK deficiency,

G6PD, Thalassaemia,Transfusion Self limiting

PARVOVIRUS Dx and TxPARVOVIRUS Dx and Tx

IgM and IgG by enzyme immunoassayAntigen by PCR or EMIgG past infectiong p

No specific treatmentBlood transfusions during crisisIVIG immunocompromised

Stephanie was in contact with Stephanie was in contact with babysitter Jodie……babysitter Jodie……

PARVOVIRUS AND PREGNANCYPARVOVIRUS AND PREGNANCY

50% seropositive so NO RISK~ 6% risk of catching in community outbreak1:400 during pregnancyRisk highest in T2Death<10%

– Spontaneous abortion– Still birth– Non-immune hydrops

No congenital problems or long term effects

Serology in pregnancySerology in pregnancy

IgG+ IgM - (Immune)IgG- IgM- (susceptible)IgG IgM+ (possible recent infection)IgG- IgM+ (possible recent infection)IgG+ IgM+ (likely recent infection)Serial US to look for hydrops

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CASE 2 ELLACASE 2 ELLA12 monthsFever for 2 daysFebrile convulsionFeeding wellDevelops rash D4

HHV 6 Roseola InfantumHHV 6 Roseola Infantum

Herpesvirus1st description 1809 (Willan)Sixth diseaseSeroprevalence 80%Most acquire by 5 yrsVeeder (Exanthem subitum)“descriptive of the most striking clinical symptom, namely, the sudden,

unexpected appearance of a rash on the fourth day”

Roseola InfantumRoseola InfantumRare < 3/12 or > 4 yrsPeak 7-13 months (20% ED visits)90% within first 2 yearsHHV 6, HHV 7 and echovirus 16,

coxsackie, enterovirus

Roseola Infantum ClinicalRoseola Infantum Clinical

Fever for 3 - 5 daysRash for 1-2 days (Blanching)Usually well childUsually well childBeliner - palpebral oedemaWBC usually lowConvulsions (6-30%)

CLINICALCLINICALHHV 6 IMMUNOCOMPROMISEDHHV 6 IMMUNOCOMPROMISED

• IMMUNOCOMPROMISED– BM suppression– Interstitial

pneumonitis

• CNS– Aseptic meningitis– FC

pneumonitis– Renal dysfunction– Skin rash

– Meningitis– ? MS flares

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DIAGNOSISDIAGNOSIS

SerologyPCR (Quantitative)

Treatment– Ganciclovir– Foscarnet– Cidofovir

CASE 3 TomCASE 3 Tom

18 months2 days of feverPost auricular

adenopathyRash‘not himself’

CluesClues

RNA virusSpread by respiratory dropletsIncubation period of 14 21 daysIncubation period of 14-21 daysCauses problems in pregnancyOften called German measles

..Also called Bastard scarlatina….?

RUBELLARUBELLA

De Bergen and Orlow (German)1881 distinct disease RubellaGregg (Australian Opthalmologist) 1941gg ( p g )Congenital defects in babiesPandemic 1964Live attenuated Rubella vaccines 1969

RUBELLARUBELLA

TogavirusOnly one antigenic typePeriodic epidemics where vaccination coverage

i lis lowTransmission by NPProlonged contact requiredMaximal shedding 5 days prior to 6 days post

appearance of rashImmunity lifelong - Ab and CMI

RUBELLA CLINICALRUBELLA CLINICAL

Incubation period 14-21 daysMild prodrome in infants and childrenPrecede the rash by 1-5 daysy yRash first on face - hands - feetDisappeared by D325% subclinical infectionLeucopenia/neutropeniaNow more common in adolescents

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RUBELLA COMPLICATIONSRUBELLA COMPLICATIONSJoints

– Arthralgia/arthritis– Rare in children– Lasts ~ 9 days– ? Association with RA

Neurological– Encephalitis rare (only 6

Other– Thrombocytopenia– Purpura– Myocarditis– Testicular pain

Haemol tic anaemiap ( y

cases in 30,000 1964)– 2 to 4 days after rash– Numbness and tingling– SSPE like illness rare

– Haemolytic anaemia

RUBELLA DIAGNOSISRUBELLA DIAGNOSIS

Specific rubella IgMCan detect from salivaRise in titre (Study IgG in paired sera)Rise in titre (Study IgG in paired sera)

Jodie was also babysitting Jodie was also babysitting Tom!Tom!

AND SHE IS 12 WEEKS PREGNANT……….

CONGENITAL RUBELLACONGENITAL RUBELLA

In utero infection first 12 weeks

CONGENITAL RUBELLACONGENITAL RUBELLAGeneral

– IUGR (50-85%)– FTT– In utero death 10-30%

Eyes– Cataracts (30%)– Unilateral or bilateral– Retinopathy (35%)

Cardiovascular– PDA (30%)– PPBS (25%)– Pulm Art hypoplasia (25%)– AS (2-5%)– TOF (2-5%)– Myocarditis (10%)

Bone– Glaucoma (5%)

Auditory– Nerve deafness (80-90%)

Neurological– Mental retardation (10-20%)– Meningoencephalitis (10-20%)– Behaviour disorders (10-20%)

Bone– Radiolucencies (20%)

Haematological– Thrombocytopenia– HSM

CONGENITAL RUBELLA CONGENITAL RUBELLA DIAGNOSISDIAGNOSIS

Virus isolation– Nose, throat, urine, buffy coat of blood, CSF– Serology difficult to interpret– Rubella specific IgM– Compare maternal to infant (drop in IgG)– Late diagnosis can be made by avidity assays

Should babies be isolated?– Yes– Carers should be known IgG+– Can shed for up to 1 yr

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What do about Jodie?What do about Jodie?

URGENT serologyIgG+ (protected)IgG- (susceptible)Watch for symptomsWatch for symptomsNasal swabSerologyIf seroconversion risk of

infection highRepeat test? Immunoglobulin

CASE 4 JACKCASE 4 JACK

18 monthsFever, coryza,

conjunctivitis x 4 days

Then rash

CASE 4 ClueCASE 4 Clue

Mouth

MEASLES (Rubeola)MEASLES (Rubeola)Endemic worldwideEpidemic disease (non vaccinated)< 1/100,000 in post vaccine eraRhazes (10th century physician)US 1st epidemic 1657Exanthem (Koplik 1896)Vaccine (live attenuated 1965)

MEASLESMEASLESRNA virus

500

400

Vaccine licensed

1963 1968 1973 1978 1983 1988 1993 1998

300

200

100

MEASLESMEASLES

Disease of childhoodPeak susceptibility infants and young

childrenchildrenTemperate climates- winter/springHighly contagiousRespiratory spread

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MEASLES CLINICALMEASLES CLINICAL

Incubation period 10 days

Prodrome lasts 2-3 days

Rash day 14From head to feetImmunity 14 days post

exposure

MEASLES CLINICALMEASLES CLINICAL

Respiratory– Common– Different appearance on

CXR– Secondary bacterial

Neurological– Abnormal EEG common– Encephalitis (1:1000)– Usually during exanthem– 25% sequelae

CSF (↑ ↑ i )y

infection– OM– LTB

Cardiac– Myocarditis– Pericarditis– ECG changes

– CSF (↑wcc, ↑protein)Others

– Black measles (haemorrhagic skin eruption)

– TP– SSPE (Dawson 1933)– 0.6/100,000– Mean incubation 7 years– Increase CSF IgG– 6-9 months until death

MEASLES MANAGEMENTMEASLES MANAGEMENT

No specific treatmentVitamin A (enhance IgG activity and total

lymphocyte numbers)100,000 IU 6/12 to 1 yr00,000 U 6 to y200,000 IU >1 yrIsolation until 5 days after rash (infectious

from prodrome)Vaccine may be used if within 72 hoursMeasles immunoglobulin

WHAT ABOUT THE CRECHE?WHAT ABOUT THE CRECHE?

Vaccinate (MMR)– Susceptible contacts if within 72 hours– Contacts 1 dose of MMR– Infants 9-12 months of age (second dose at 12 months)

M l I l b liMeasles Immunoglobulin– IM injection within 7 days of exposure– 0.2ml/kg (max 15 ml)– > 9 months if MMR contraindicated– Non immune pregnant women– Impaired immunity– Infants 6-9 months (followed 5 months later by MMR)

If no vaccine exclude from school for 14 days

AND CAN YOU BELIEVE IT…..AND CAN YOU BELIEVE IT…..

• Jodie picked up her son at the creche were Jack was

• Pregnancy– Premature labour– Still birth– Spontaneous abortion– Check serology– If negative give

immunoglobulin

RASHES WITH VESICLESRASHES WITH VESICLES

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CASE 5 JimCASE 5 Jim

3 year oldFever and rashVesicular rash++ itchy

VARICELLAVARICELLA

DNA virusOne antigenic typePrimary infection-varicellayReactivation-shingles (Zoster)Highly contagious (80-90% attack rates)Incubation period 14-16 daysInfectious from 48 hr prior to rash until

crusting of lesions

VARICELLA CHICKENPOX VARICELLA CHICKENPOX

“Chickenpox”French pois chiche (chick pea)Farmyard fowl (Cicen)Farmyard fowl (Cicen)German (kuchen)Herpes Greek “to creep”Zoster “girdle’ or “belt”

VARICELLA TRANSMISSIONVARICELLA TRANSMISSION

Airborne routeDirect contactZoster not transmissibleZoster not transmissible

VARICELLA VARICELLA

Pre-vaccine 3.8M cases annually USLive attenuated vaccine licensed in 1995Zoster 15% over a lifetimeZoster rare in children

– More common in children with in utero infection– Infection prior to 2 yrs (RR 3-21)– HIV infected children with CD4% <15%

VARICELLAVARICELLA

5% subclinical (75% adults seropositive with no history of clinical varicella)

85% seropositive by 10-15 yrs85% seropositive by 10 15 yrsPrior to vaccine 240,000 cases in Aus1500 hospitalisations7-8 deaths per year

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VARICELLA CLINICALVARICELLA CLINICAL

200-500 skin lesionsMouth, conjunctivaLimited prodrome in childrenLimited prodrome in childrenMore likely in adults

VARICELLA COMPLICATIONSVARICELLA COMPLICATIONS

Bacterial superinfection– SA, GAS

CNS– Aseptic meningitis– Cerebellar ataxia– Transverse myelitis– Reye (aspirin use)

Arthritis, myocarditis, GNVaricella pneumonia in IC

ZOSTERZOSTER

Dermatomal distributionPainful in adultsPHNPHNIF/ Culture from skin lesions

TREATMENTTREATMENT

SupportiveAcyclovirIV acyclovirIV acyclovirFamciclovir

VARICELLA EXPOSUREVARICELLA EXPOSURE

Post exposure – Varicella vaccine within 72 hours but up to 5 days

Household contacts– Household contacts of those with impaired

immunity

Healthcare workers– If vaccinated watch for rash for 3 weeks– If unvaccinated or uncertain history (vaccine)– If does not want vaccination (reassign or place on

sick leave from D 10-21)

Zoster ImmunoglobulinZoster ImmunoglobulinPublic Health

– ZIG within 96 hours to pregnant women if susceptible

– ZIG to neonates whose mother develops VZV from 7 days prior to 2 days after deliveryZIG t t i th fi t 30 d if th – ZIG to neonates in the first 30 days if mother no history or negative serology

– Premature infants <28 weeks– IC where vaccine may be contraindicated

Dose– 0- 10 kg 200IU– 11-30 kg 400 IU– > 30 kg 600 IU

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VARICELLA VARICELLA IMMUNOCOMPROMISEDIMMUNOCOMPROMISED CMVCMV

DNA virusFirst described in 1881(Ribbert)Initially in salivary glands (Salivary gland Initially in salivary glands (Salivary gland

virus)60-70% seroprevalence

CMVCMV

CMV acquisition– Exposure in the home– SES– Daycare exposure– Prevalence rates of 20-50% in daycare

No seasonal variationMost common cause of congenital

infection

CMV TRANSMISSIONCMV TRANSMISSION

Direct person to person spreadIntimate contact with secretionsExcretion starts 4 6 weeks following Excretion starts 4-6 weeks following

infectionMay persist for years

CMV TRANSPLANTCMV TRANSPLANT

Primary, reinfection, reactivationD+/R-CMV pneumonitis BMT > renal> liver CMV pneumonitis BMT > renal> liver

patientsProphylaxis

CMV CLINICALCMV CLINICAL

>90% asymptomaticFever and malaise up to 4

weeksHeadacheMyalgias

OrganomegalyImmunocompromised

– Fever– Leucopenia

MyalgiasAbdominal painDiarrhoea

RashCMV pneumonia

– IC

– Transaminitis– Pneumonitis– Enterocolitis– Retinitis– Encephalitis– 1-4 months post transplant

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CMV POST TRANSPLANTCMV POST TRANSPLANT CMV DIAGNOSISCMV DIAGNOSIS

SerologyCMV IgG persists for lifeCaution in ICIgM interpretation

Biopsy – Tissue culture

PCRIgM interpretationRemove RFCMV IgM 6 weeks and may

persist for monthsAvidity

CMV antigenaemiaRegular monitoring in

IC

CMV TREATMENTCMV TREATMENT

Medications– Ganciclovir– Valganciclovir– Cidofovir

Prevention– CMV - blood– Hyperimmune globulin

Prophylactic anti viralsCidofovir– Foscarnet

IC– Induction (IV) and

maintenanceImmunoglobulinCMV Hyperimmune globulin

– Prophylactic anti-virals– Hygiene– Leucocyte depleted

blood– ? Vaccine– Viral surveillance

CMV pregnancyCMV pregnancy

• What are the options?

CMV PREGNANCYCMV PREGNANCY

Nigro et al 2008

CASE 7 JohnCASE 7 John

7 years old– Sore throat– Fatigue– Fever 2 weeks– Lymphadenopathy– Splenomegaly

– In his throat…

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CASE 7 JohnCASE 7 John

• 7 years old– Blood film

EBVEBV

Pfeiffer 1889“ Drusenfeiber” Glandular feverInitially suggestive of leukaemia1930s Paul and Bunnell (high heterophile abs in a 1930s Paul and Bunnell (high heterophile abs in a

medical student with EBV)1958 Dennis Burkitt (Epstein et al noted viral particles

similar to HSV - HHV 4)Serendipity 1968 Lab technician seroconverted with

EBV (6 days after getting symptoms)

EBVEBV

DNA virusEBV 1 and 2Lytic infection in oropharyngeal cellsy p y gInfects B cellsEstablished latency in B cells (1-50 /1,000,000)

EBM TRANSMISSIONEBM TRANSMISSION

Kissing diseaseEBV not transmitted efficientlyIncubation period 30 50 daysIncubation period 30-50 days

EBV CLINICALEBV CLINICAL

Acute Phase– Fever 1-2 weeks– Sore throat– Lymphadenopathy (W 2-4)– Tonsillopharyngitis (W 1)– Splenomegaly (50%)

Hepatomegaly (60%)

HLH– 1939– Fever– Pancytopenia– Splenomegaly– Haemophagocytosis– XLPD

Malignancy– Hepatomegaly (60%)– Rash

Resolution phase– 3-4 wks– Enlarged nodes 3-4 M– Severe fatigue– CFS no clear association

Malignancy– BL- African and PNG– Jaw>abdominal– HD

Complications– Rare– Neurological (1-5%)– ITP (20-50%)– Neutropenia– Cardiac– Respiratory (AO 1-5%)– Neck abscesses

EBV DIAGNOSISEBV DIAGNOSIS

FBE + Film– Lymphocytosis– Atypical Lymphocytes– Low plts

Serology– IgM VCA– IgG VCA– EA antibodies

Heterophile abs– Agglutination of

sheep/horse RBCs– Rapid test (Monospot)– False positive and

negatives

EA antibodies– EBNA later

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EBV serologyEBV serology EBV TREATMENTEBV TREATMENT

SupportiveAnti-virals: acyclovir,penciclovir, GCVDecrease viral sheddingDecrease viral sheddingRituximab (anti-CD20)Chemotherapy

CASE 8 OliviaCASE 8 Olivia

5 month old babyUnwell x 2-3 daysPoor feedingR i diRespiratory distress

CXR

RSVRSV

Most important respiratory pathogen

91,000 admissions USInfects nearly all children in

Spreads efficiently (older sib likely to infect young)

RVS remains infectious on counter tops for 6 hours

the first few yearsFirst discovered in

chimpanzeesRNA virusPassive protectionPeak 2-5/12M>F severity

Direct contact

RSVRSV

Incubation period 4-6 days

1% of primary infections lead to hospitalisation

Pulse oximetry may prolong admission

CXR rarely needed for diagnosisHandwashinglead to hospitalisation

Rhinitis, Fever, rales, wheezes, hypoxaemia, apnoea

Duration 7-12 daysFull recovery may take

weeks

Apnoea– 20% of hospitalised infants – < 44 weeks

RSVRSV

Diagnosis– Clinical– IFA from respiratory

specimen (nasal swab or

Treatment– Supportive– 02– Bronchodilators

NPA)– Serology not helpful in

acute setting

Bronchodilators controversial

– Steroids not useful– Ribavirin

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RSV PREVENTIONRSV PREVENTION

Breast feedingRSV immunoglobulin

– < 24/12 *gestational age < 36 weeks– < 24/12 gestational age < 36 weeks– Pre-term with CLD– Administered during RSV season– Expensive– No vaccine

Human MetapneumovirusHuman Metapneumovirus

First described in 2001Illness similar to RSVAffects children < 2 yearsM hild i i b 5 Most children seropositive by age 5 yrsNo specific treatmentDiagnosis by PCRNo IF test available

CASE 9 JAMESCASE 9 JAMES

4 yrs oldRash on palms and

sole of feetFever

..you get a brief look in his mouth

ENTEROVIRUSENTEROVIRUS

Sore throat, feverBlisters on palms and soles of feetVesicular lesions on buccal

surfacesSymptomatic management

Humans only natural hostsSpread by F-O routeIncubation 3-6 days

N l i lSymptomatic management

Other Coxsackie viruses– A 1-24– B1 -6

Echovirus 1-34Enterovirus 68-71Poliovirus 1-3

Neurological– Aseptic meningitis– Encephalitis– CSF findings variable– Early neutrophil

predominance– Possible sequelae

– Pleconoril no longer used

CASE 10 EVACASE 10 EVA

2/5/20083/12 girl presenting with cough

HOPCHOPC2/52:

– Staccato like cough– Poor oral intake– Gagging and vomiting post cough– Coryza

BackgroundBackground

Birth Hx– Born Tanzania– Nil Antenatal concerns – routine Ix NAD– 42/40 NVD– BW 3.285g

Social/FHx: Tanzanian mother – dental nurseMother HIV negative at 6/12 pregnancyAustralian father – engineer Arrived in Australia 2/52 prior for holiday

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BackgroundBackground

PHx: Breast Feeding with appropriate weight gain to

date date. Nil developmental concerns

IUTD – inc BCGMeds – Nil regularNKDA

Examination FindingsExamination Findings

On presentationSats 85% RABP 85/60 RR 70 PR 160BP 85/60, RR 70, PR 160Moderate respiratory distress

Additional findings on Additional findings on examinationexamination

oral thrushsplenomegalyhepatomegaly small BCG scar no other rashessmall BCG scar, no other rashes

Ix• FBE – Hb 118, Plat 196, WCC 11.5, N3.2, L7.2• CXR

Differential DiagnosisDifferential DiagnosisInfective

– Viral – RSV, CMV or other viral infection– Atypical pneumonia - Chlamydia / mycoplasma– Congenital or miliary TB – Bacterial pneumoniaBacterial pneumonia– HIV +/-PCP

Structural– Tracheomalacia– H type TOF

Infiltration– Leukaemia

InvestigationsInvestigations

• FBE:– Hb 104, Plat 189, WCC 4.7 neuts 2.72

lymphocytes 1.83y p y

• LFTS: albumin 19• U&E – N• NPA – RSV + (DIF)

Further IxFurther Ix

HIV antibodies – positive (WB, ELISA)NPA – PCP PCR +HIV tests organised on parents (discordant results)HIV tests organised on parents (discordant results)

U/S - Enlarged spleen with multiple scattered hypoechoic lesions. ?infective ? Infiltrative ? TB ? Fungal

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Further InvestigationsFurther Investigations

HIV HIV RNA PCR - >750,000 copies/mlCD4 13% (absolute 237) (23-60)CD8 47% (14-25)

CMVNPA and urine culture +BAL culture +IgG Neg and IgM +CMV blood quantitative viral load 2x10^3 copies/mL (5/5)

Global view of HIV

Western & Central Europe

<100<100[[<100 –– <200]]

Middle East & North Africa46004600

Eastern Europe & Central Asia

3700 3700 [1700 [1700 –– 6000]6000]

South & South East

North America<<100

[<100 –– <200]East Asia

32003200[2100 [2100 –– 4500]4500]Caribbean

2300

Estimated number of children (<15 years) Estimated number of children (<15 years) newly infected with HIVnewly infected with HIV

46004600[2300 [2300 –– 7500]7500]

Sub-Saharan Africa390 000390 000

[210 000 [210 000 –– 570 000]570 000]

South & South-East Asia18 00018 000

[11 000 [11 000 –– 25 000]25 000]Oceania

<500<500[<500 –– <1000]

Latin America69006900

[4200 [4200 –– 9700]9700]

2300[1400 – 3400]

Total: 430 000 (240 000 – 610 000)An estimated 1200 children infected daily

HIVHIV

• Vertical transmission• 25-30% die by 1 yr• <1% infection rate in

developed countriesdeveloped countries• ART effective if can access• More resources• Diagnosis often too late

HIV virionHIV virion HIV life cycleHIV life cycle

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Transmission – When?

Courtesy Deepak Patel

100 infants born to HIV-infected women who breastfeed, without any interventions

60 to 75 infants will not be HIV-infected

5–10 infected during

About 15 infected during

5–15 infected during

What are the chances?..............

25 to 40 will be HIV-infected

pregnancy labour and delivery

breast-feeding

Courtesy Deepak Patel

Vertical TransmissionVertical Transmission• Accounts for >90% paediatric HIV

– Risk if HIV positive mother• Europe ~14%, Africa ~30%

• In utero - from 1st trimesterIn utero from 1 trimester• Intrapartum – 50-70% vertical

transmission– Contact with infected secretion or blood

• Postpartum – 14-29%*– Breastfeeding

Risk factors for vertical Risk factors for vertical infectioninfection

Advanced maternal disease/low CD4High viral loadNVD (vs LUSCS) when detectable VLNVD (vs LUSCS) when detectable VLROM > 4 hoursMonitoring -FSBloody deliveryBreast feeding

What can we do? What can we do?

Maximise maternal status– Health, nutrition

Diminish viral load raise CD4 %Diminish viral load, raise CD4 %– Maximise anti-retroviral regimen by

delivery

Don’t breast feed

Vertical TransmissionVertical Transmission--Antiretroviral treatment:Antiretroviral treatment:

ACTG 076– Maternal zidovudine (ZDV) po from 34/40– ZDV IV during labourZDV IV during labour– Oral ZDV to infant for 1st 6 weeks– Reduced risk from 25.5% to 8.3%

Maternal HAART (3 drugs)– Risk of transmission 1:1000

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Increasing number of HIV infected women delivering in Victoriadelivering in Victoria

Currently in past two years ~ 60 women

Service development in Melbourne-

Dr Michelle Giles (ID)Dr Olga Vugovic (ID)Dr Tom Connell (PID)Louise BordunDr Penelope Bryant (PID)Prof Richard Doherty (PID)Jane HowardKaren Blyth

Obstetrician

ID Physician GP

Paediatrician

Nurse specialists

PharmacistRWH

MMC

RCH

Prevention of Infection

ARTART

Reverse transcriptase inhibitorsNucleoside analogues (NRTIs)Nucleotide analogues (NRTIs-Tenofovir,abacavir)

Non nucleoside RTIs (NNRTIs)Interfere with binding at the active site of the RT

Protease inhibitors (PIs)

Probability of Death/AIDS within 12 months by CD4

Courtesy Hermione Lyall

Probability of Death/AIDS within 12 months by VL and age

Courtesy Hermione Lyall

NOVEL AGENTSNOVEL AGENTSNNRTIs

– TMC125 (Etravirine)Protease inhibitors

– TMC 114 (Darunavir)Maturation inhibitors

– PA-457CCR5 antagonists

– Maraviroc, VicrivirocFusion inhibitors

– T651Integrase inhbitors

– MK0518, GS9137

HIV viral cycleHIV viral cycle

Co‐receptor antagonist

Fusion inhibitor

ZidovudineStavudineDidanosine

Enfuvirtide (T20)MaravirocVicriviroc

NRTI

NNRTI

Integrase inhibitor

Protease inhibitor

DidanosineLamivudineAbacavirTenofovirEmtricitabine

NevirapineEfavirenzEtravirine

LopinavirRitonavirAtazanavirDarunavirIndinavirNelfinavirSaquinavirTipranavir

RaltegravirElvitegravir

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ARTART

WHO 2008

Meds do not taste nice!

Vertical TransmissionVertical Transmission--management of newborn:management of newborn:

Diagnostic PCR:– 1st within 48 hrs pick up 38%– 2nd at 2-4 weeks pick up 93%– 3rd at 4 months pick up 99.7%p p

serology at 12-18 months

INFLUENZAINFLUENZA

“last greatest plague of man”Epidemic 412 BC300 000 hospitalisations annually300,000 hospitalisations annually8 influenza pandemics since 15801918 (20 M deaths worldwide)Orthomyxovirus

INFLUENZAINFLUENZA

RNA virusSurface glycoproteins Haemagluttinin

(HA)(HA)Neuraminadase (NA)

INFLUENZAINFLUENZA

Droplet spreadIncubation 1-7 daysViral shedding shorter for Influenza AViral shedding shorter for Influenza AHumoral and cell mediated immunityAnti HA - neutralisationAnti-NA- decrease severitySecretory IgA

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INFLUENZA CLINICALINFLUENZA CLINICAL

Clinical– Abrupt onset– Fever 2-3 days– Chills

Complications– Bacterial infections– Myositis– Encephalopathy

– Headache– Myalgia

PneumoniaGIT

– Abdominal pain– Anorexia

– Reye syndrome– Cardiac– Sudden death

TreatmentAmantadine (A)Inhaled zanamivir (A/B)Oseltamavir (A/B)

H1N1 swine flu H1N1 swine flu

• 40000 confirmed cases• Very infectious• High risk in pregnant women• High risk in pregnant women• 200 deaths• Vaccine