6/01/2011

PLAN Dr Tom Connell Infectious Disease Physician Quiz Classification of viruses VIRAL Cases and descriptions Viruses 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”

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

CMV QUIZ EBV HHV-8 HIV HPV

2. 2 yr old. Lesions on 3. Day 3 MRI, HSM, Purpuric rash Microcephaly hands and feet What is the most likely Fever 38 C diagnosis?

Coxackie A16 CMV EBV HSV HSV-1 HHV-6 Syphilis Toxoplasmosis

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4. In developed countries, breast feeding is 5. is most commonly contraindicated by which of the following maternal infections? associated with which of the following? CMV Bronchiolitis Croup Febrile convulsion HIV Viral

6. Which of these signs is not associated with 7. Term infant. Mum Hep B +. What is the most congenital CMV? appropriate management of infant?

Anaemia Hep B vaccine Cataract Hep B vaccine and immunoglobulin Chorioretinitis Check LFTs Hepatosplenomegaly Withhold hepatitis B vaccine IUGR Exclusion of breats milk

8. 7 year old finished intensive chemo. WBC 9. Which one of the following virus families is 1.1 In contact with VZV. What is the most are not RNA viruses? appropriate management?

VZIG Hepadna IV aciclovir Paromyxovirus Intragam Coronovirus Oral ACV Flavivirus Varicella vaccine Togavirus

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10. Which of the following statements 11. Which of the following conditions has not concerning Parvovirus B 19 is NOT true? been associated with parvoviral ?

DNA virus Glomerulonephritis Incubation period 4-16 days Parotitis Also called Chronic fatigue syndrome Mainly affects young children Meningitis The majority of infections are Purpuric rash asymptomatic

12. Which one of the following statements 13. Which one of the following concerning parvovirus in pregnancy is true? statements is true in relation to HHVHHV--6?6?

Risk highest in the first trimester Causes fifth disease Intruterine death is common Most children acquire infection by age 2 Long term effects are common years 1:1000 during pregnancy Also called exanthem subitum IgG+/Igm- maternal serology indicates immunity Seroprevalence is low High mortality

14. Which one of the following conditions is 15. In a outbreak/contact, which of NOT associated with congenital rubella? the following measures is most appropriate?

Chorioretinitis Infants age 9-12 months should be give one MMR vaccine that will cover for the 12 IUGR month immunisation Deafness Measles immunoglobulin should be administered to all contacts PDA Exclude from school for 7 days Thrombocytopenia MMR vaccine should be given to susceptible if within 72 hours

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

High mortality in general population Untreated the chance of MTCT is 30% Vaccine associated with high risk of GBS CMV is not an AIDS defining illness Influenza Infected infants < 12 months should be treated based on VL and CD4 count Oseltamavir is contraindicated in HIV-infected mothers should not pregnancy breastfeed Incubation period 3-5 days With treatment in pregnancy rates of transmission < 1%

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 19. Which of the following medications is most 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 likely to be used to treat Hepatitis B infection? there had been a significant exposure? Acyclovir HIV 10%, Hep B 3%, Hep C, 30%, Ganciclovir HIV 0.3%,,p Hep B 30% ,p, Hep C 3% Lamivudine HIV 30%, Hep B 3%, Hep C 0.3% Interferon gamma HIV 0.1%. Hep B 1%, Hep C 10% Vidarabine

20. Which of these situations concerning 21. Which is not a category of antianti--retroviralretroviral maternal HSV is associated with the greatest medications? risk to the baby? Mother has recurrent genital HSV- Nucleoside reverse transcriptase infection inhibitors Mother acquires infection with HSV-2 Non-nucleoside reverse transcriptase having had HSV-1 (non-primary) inhibitors Mother has primary HSV-1 early in Fusion inhibitors pregnancy CCR4 antagonists Mother has primary HSV-1 at 34 weeks

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22. WHO recommends treating which of the 23. Which strain was responsible for the following with HIV? swine flu pandemic?

All infants less than 1 yr of age H3N2 Only infants with CD4% <25 H5N1 Only infants with VL>100, 000 H1NI No infants as they are at less risk H2N3

24. Estimated number of confirmed 25. Estimated number of deaths due to swine cases of swine flu in Australia in 2009? flu in Australia in 2009

40 20 400 200 4000 2000 40000 20000

2 yr old. Lesions on hands 1. Which of the following viruses has not been and feet associated with malignancy? Fever 38 C CMV Coxackie A16 EBV EBV HHV-8 HSV-1 HIV HHV-6 HPV Parvovirus B19

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3. Day 3 MRI, HSM, 4. In developed countries, breast feeding is Purpuric rash, contraindicated by which of the following maternal Microcephaly infections? What is the most likely diagnosis? CMV CMV Hepatitis A HSV Hepatitis B Rubella Hepatitis C Syphilis HIV Toxoplasmosis

5. Human metapneumovirus is most commonly 6. Which of these signs is not associated with associated with which of the following? congenital CMV?

Bronchiolitis Anaemia Croup Cataract Febrile convulsion Chorioretinitis Gastroenteritis Hepatosplenomegaly Viral exanthem IUGR

8. 7 --yearyear old finished intensive chemo. WBC 7. Term infant. Mum Hep B and C +. What is 1.1 In contact with VZV. What is the most the most appropriate management of infant? appropriate management? Hep B vaccine VZIG Hep B vaccine and immunoglobulin IV aciclovir Check LFTs Intragam Withhold hepatitis B vaccine Oral ACV Exclusion of breats milk Varicella vaccine

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9. Which one of the following virus families is 10. Which of the following statements not an RNA virus? concerning Parvovirus B 19 is NOT true?

Hepadna DNA virus Paromyxovirus Incubation period 4-16 days Coronovirus Also called fifth disease Flavivirus Mainly affects young children Togavirus The majority of infections are asymptomatic

11. Which of the following conditions has been 12. Which one of the following statements not been associated with parvoviral infection? concerning parvovirus in pregnancy is true

Glomerulonephritis Risk highest in the first trimester Parotitis Intrauterine death is common Chronic fatigue syndrome Long term effects are common 1:1000 during pregnancy Meningitis IgG+/IgM- maternal serology indicates Purpuric rash immunity

13. Which one of the following 14. Which one of the following conditions is statements is true in relation to HHVHHV--6?6? NOT associated with congenital rubella?

Causes fifth disease Chorioretinitis Most children acquire infection by age 2 IUGR years Deafness Also called exanthem subitum PDA Seroprevalence is low Thrombocytopenia High mortality

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16. Which of the following statements is 15. In a measles outbreak/contact, which of true concerning swine flu influenza? the following measures is most appropriate?

Infants age 9-12 months should be give one MMR High mortality in general population vaccine that will cover for the 12 month immunisation Vaccine associated with high risk of GBS Measles immunoglobulin should be administered to all contacts Exclude from school for 7 days Oseltamavir is contraindicated in MMR vaccine should be given to susceptible if within pregnancy 72 hours Incubation period 3-5 days

18. 3 year old John was found by his mum with a syringe in his 17. Which of the following statements is NOT hand. He was crying and it appeared that there was a small puncture wound to his hand. Which of the following is true true in relation to HIV infection? concerning his risk of viral infection with Hep B, Hep C and HIV if there had been a significant exposure? Untreated the chance of MTCT is 30% CMV is not an AIDS defining illness HIV 10%, Hep B 3%, Hep C, 30%, Infected infants < 12 months should be HIV 0.3%,,p Hep B 30% ,p, Hep C 3% treated based on VL and CD4 count HIV 30%, Hep B 3%, Hep C 0.3% HIV-infected mothers should not HIV 0.1%. Hep B 1%, Hep C 10% breastfeed With treatment in pregnancy rates of transmission < 1%

19. Which of the following medications is most 20. Which of these situations concerning likely top be used to treat Hepatitis B maternal HSV is associated with the greatest infection? risk to the baby? Acyclovir Mother has recurrent genital HSV- Ganciclovir infection Lamivudine Mother acquires infection with HSV-2 Interferon gamma having had HSV-1 (non-primary) Vidarabine Mother has primary HSV-1 early in pregnancy Mother has primary HSV-1 at 34 weeks

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21. Which is not a category of antianti--retroviralretroviral 22. WHO recommends treating which of the medications? following with HIV?

Nucleoside reverse transcriptase All infants less than 1 yr of age inhibitors Only infants with CD4% <25 Non-nucleoside reverse transcriptase Only infants with VL>100, 000 inhibitors No infants as they are at less risk Fusion inhibitors CXCR4 antagonists

23. Which strain was responsible for the 24. Estimated number of confirmed swine flu pandemic? cases of swine flu in Australia in 2009?

H3N2 40 H5N1 400 H1NI 4000 H2N3 40000

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

20 200 2000 20000

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Classification of Viruses Classification of Viruses Herpes HHV 6 EBV CMV Molluscum HPV Rubeola Adenovirus Rubella Parvovirus Rhinovirus Influenza Parainfluenza Enterovirus Coxsackie HIV

CASE 1 Stephanie

Febrile ~ 1 week ago FEVER WITH RASH Rash Rash over trunk and extremities Pale

PARVOVIRUS B19 Clues Erythema infectiosum (Stricker 1899) Fifth disease DNA virus DNA virus 1st known human parvovirus (discovered in This disease is also a number petri dish B19) Grows only in dividing cells Spread - direct contact with secretions (group Also called slapped cheek of volunteers infected nasally with B19) Can be transmitted by blood transfusion And the answer …….. Incubation period 4-15 days

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PARVOVIRUS B19 PARVOVIRUS B19

Epidemic pattern similar to Rubella Non specific fever Erythema infectiousum Most prevalent in winter and spring Virus shedding between D 5 and D 12 Virus excretion IgM Attack rate highest in children 5 to 14 yrs SitiSeropositive (IG)(IgG)

2 to 21% of children < 11yrs Reticulocytes

40 to 60% adults Viraemia Pathophysiology and pathology – Direct effects (lysis)

– Indirect (immune) 07 14 21 28

B19 inhibits the formation of blast forming erythroid colonies

PARVOVIRUS B19 CLINICAL Erythema Infectiosum Prodromal phase 2-3 days (viraemia) Spectrum Symptom free for 7 days 20% asymptomatic D18- “slapped cheek” Facial exanthem worsens on going from Usual erythema infectiosum outdoors to warm room Unusual clinical manifestations D 19-23 maculopapular rash on trunk Headache in 20% Arthralgia (80% adults, <10% children) Knees, ankles, PIPJ, bilateral No isolation

PARVOVIRUS RARE CLINICAL

Arthritis (association between B19 •Other Stephanie comes back….. and RA) –GN Neurological – Kawasaki – Encephalitis (B19 DNA CSF) –Meningitis –Behcet – GB syndrome –PAN – Facial palsy Rash has gone… – CT syndrome – Wegener’s (5 children and 4 – Hepatitis adults) –SLE But she is very Cutaneous – Raynaud –EM – Parotitis pale… –HSP – Hepatitis – Petechiae Haematological – Pseudoappendicitis – TTP –CFS –Pancytopenia – Chronic haemolytic – Haemophagocytic anaemia WHY?? – DB anaemia

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PARVOVIRUS B19 APLASTIC CRISIS

Non specific fever Erythema infectiousum Reticulocytopenia Aplastic crisis Decreased RCC lifespan Virus excretion IgM SCA, HS, PK deficiency, G6PD, Thalassaemia

Reticulocytes Transfusion Viraemia Self limiting

07 14 21 28

B19 inhibits the formation of blast forming erythroid colonies

Stephanie was in contact with PARVOVIRUS Dx and Tx babysitter Jodie…… IgM and IgG by enzyme immunoassay Antigen by PCR or EM IggpG past infection

No specific treatment Blood transfusions during crisis IVIG immunocompromised

PARVOVIRUS AND PREGNANCY Serology in pregnancy

50% seropositive so NO RISK IgG+ IgM - (Immune) ~ 6% risk of catching in community outbreak IgG- IgM- (susceptible) 1:400 during pregnancy Risk highest in T2 IgG- IgM+ (possible recent infection) Death<10% IgG+ IgM+ (likely recent infection) – Spontaneous abortion Serial US to look for hydrops – Still birth – Non-immune hydrops No congenital problems or long term effects

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CASE 2 ELLA HHV 6 Infantum

12 months Herpesvirus Fever for 2 days 1st description 1809 (Willan) Febrile convulsion Sixth disease Feeding well Seroprevalence 80% Most acquire by 5 yrs Develops rash D4 Veeder (Exanthem subitum) “descriptive of the most striking clinical symptom, namely, the sudden, unexpected appearance of a rash on the fourth day”

Roseola Infantum Rare < 3/12 or > 4 yrs Roseola Infantum Clinical Peak 7-13 months (20% ED visits) Fever for 3 - 5 days 90% within first 2 years Rash for 1-2 days (Blanching) HHV 6, HHV 7 and echovirus 16, Usually well child coxsackie, enterovirus Beliner - palpebral oedema WBC usually low Convulsions (6-30%)

CLINICAL HHV 6 IMMUNOCOMPROMISED

• IMMUNOCOMPROMISED •CNS – BM suppression – Aseptic meningitis – Interstitial –FC pneumonitis –Meningitis – Renal dysfunction –? MS flares –Skin rash

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DIAGNOSIS CASE 3 Tom

Serology Treatment 18 months PCR (Quantitative) – Ganciclovir 2 days of fever –Foscarnet Post auricular – Cidofovir adenopathy Rash ‘not himself’

Clues RUBELLA

RNA virus De Bergen and Orlow (German) Spread by respiratory droplets 1881 distinct disease Rubella Incubation period of 14-21 days Gregg ( Australian O pthalmolo gist ) 1941 Congenital defects in babies Causes problems in pregnancy Pandemic 1964 Often called German measles Live attenuated Rubella vaccines 1969

..Also called Bastard scarlatina….?

RUBELLA RUBELLA CLINICAL

Togavirus Incubation period 14-21 days Only one antigenic type Mild prodrome in infants and children Periodic epidemics where vaccination coverage Precede the rash by 1-5 days is low Rash first on face - hands - feet Transmission by NP Prolonged contact required Disappeared by D3 Maximal shedding 5 days prior to 6 days post 25% subclinical infection appearance of rash Leucopenia/neutropenia Immunity lifelong - Ab and CMI Now more common in adolescents

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RUBELLA COMPLICATIONS Joints Other RUBELLA DIAGNOSIS – Arthralgia/arthritis – Thrombocytopenia – Rare in children – Lasts ~ 9 days –Purpura Specific rubella IgM – ? Association with RA – Myocarditis Neurological –Testicular pain Can detect from saliva –Encepp(yhalitis rare (only 6 cases in 30,000 1964) – Haemolytic anaemia Rise in titre (Study IgG in paired sera) – 2 to 4 days after rash – Numbness and tingling – SSPE like illness rare

Jodie was also babysitting CONGENITAL RUBELLA Tom! In utero infection first 12 weeks AND SHE IS 12 WEEKS PREGNANT… …….

CONGENITAL RUBELLA CONGENITAL RUBELLA General Cardiovascular – IUGR (50-85%) – PDA (30%) DIAGNOSIS –FTT – PPBS (25%) – In utero death 10-30% – Pulm Art hypoplasia (25%) Virus isolation Eyes – AS (2-5%) – Nose, throat, urine, buffy coat of blood, CSF – Cataracts (30%) – TOF (2-5%) – Unilateral or bilateral – Serology difficult to interpret – Myocarditis (10%) – Retinopathy (35%) – Rubella specific IgM Bone –Glaucoma (5%) – Compare maternal to infant (drop in IgG) – Radiolucencies (20%) Auditory – Late diagnosis can be made by avidity assays – Nerve deafness (80-90%) Haematological Neurological – Thrombocytopenia – Mental retardation (10-20%) –HSM Should babies be isolated? – Meningoencephalitis (10-20%) –Yes – Behaviour disorders (10-20%) – Carers should be known IgG+ –Can shed for up to 1 yr

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What do about Jodie? CASE 4 JACK

URGENT serology 18 months IgG+ (protected) Fever, coryza, IgG- (susceptible) conjunctivitis x 4 Watch for symptoms days Nasal swab Serology Then rash If seroconversion risk of infection high Repeat test ? Immunoglobulin

MEASLES (Rubeola) CASE 4 Clue Endemic worldwide Mouth Epidemic disease (non vaccinated) < 1/100,000 in post vaccine era Rhazes (10th century physician) US 1st epidemic 1657 Exanthem (Koplik 1896) Vaccine (live attenuated 1965)

MEASLES MEASLES RNA virus 500 Vaccine licensed Disease of childhood

400 Peak susceptibility infants and young

300 children Temperate climates- winter/spring 200 Highly contagious 100 Respiratory spread

1963 1968 1973 1978 1983 1988 1993 1998

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MEASLES CLINICAL MEASLES CLINICAL

Incubation period 10 Respiratory Neurological – Common – Abnormal EEG common days – Different appearance on – Encephalitis (1:1000) CXR – Usually during exanthem Prodrome lasts 2-3 –Secondary bacterial – 25% sequelae days infection – CSF (↑wcc, ↑protei)in) –OM Others – Black measles (haemorrhagic Rash day 14 –LTB skin eruption) Cardiac –TP From head to feet – Myocarditis – SSPE (Dawson 1933) Immunity 14 days post – – 0.6/100,000 – ECG changes – Mean incubation 7 years exposure –Increase CSF IgG – 6-9 months until death

MEASLES MANAGEMENT WHAT ABOUT THE CRECHE?

No specific treatment Vaccinate (MMR) Vitamin A (enhance IgG activity and total – Susceptible contacts if within 72 hours lymphocyte numbers) – Contacts 1 dose of MMR – Infants 9-12 months of age (second dose at 12 months) 100,000 IU 6/12 to 1 yr MlMeasles Immunog lblilobulin 200,000 IU >1 yr – IM injection within 7 days of exposure Isolation until 5 days after rash (infectious – 0.2ml/kg (max 15 ml) – > 9 months if MMR contraindicated from prodrome) – Non immune pregnant women Vaccine may be used if within 72 hours – Impaired immunity – Infants 6-9 months (followed 5 months later by MMR) Measles immunoglobulin If no vaccine exclude from school for 14 days

AND CAN YOU BELIEVE IT…..

• Jodie picked up her son at the creche were Jack was RASHES WITH VESICLES •Pregnancy – Premature labour – Still birth – Spontaneous abortion –Check serology – If negative give immunoglobulin

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CASE 5 Jim VARICELLA

3 year old DNA virus Fever and rash One antigenic type Vesicular rash Primary infection-varicella ++ itchy Reactivation- (Zoster) Highly contagious (80-90% attack rates) Incubation period 14-16 days Infectious from 48 hr prior to rash until crusting of lesions

VARICELLA VARICELLA TRANSMISSION

“Chickenpox” Airborne route French pois chiche (chick pea) Direct contact Farmyard fowl (Cicen) Zoster not transmissible German (kuchen) Herpes Greek “to creep” Zoster “girdle’ or “belt”

VARICELLA VARICELLA

Pre-vaccine 3.8M cases annually US 5% subclinical (75% adults seropositive Live attenuated vaccine licensed in 1995 with no history of clinical varicella) Zoster 15% over a lifetime 85% seropositive by 10-15 yrs Zoster rare in children Prior to vaccine 240,000 cases in Aus – More common in children with in utero infection – Infection prior to 2 yrs (RR 3-21) 1500 hospitalisations – HIV infected children with CD4% <15% 7-8 deaths per year

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VARICELLA CLINICAL VARICELLA COMPLICATIONS

200-500 skin lesions Bacterial superinfection Mouth, conjunctiva –SA, GAS CNS Limited prodrome in children – Aseptic meningitis More likely in adults – Cerebellar ataxia – Transverse – Reye (aspirin use) Arthritis, myocarditis, GN Varicella pneumonia in IC

ZOSTER TREATMENT

Dermatomal distribution Supportive Painful in adults Acyclovir PHN IV acyclovir IF/ Culture from skin lesions Famciclovir

VARICELLA EXPOSURE Zoster Immunoglobulin

Public Health – ZIG within 96 hours to pregnant women if Post exposure susceptible – Varicella vaccine within 72 hours but up to 5 days – ZIG to neonates whose mother develops VZV from Household contacts 7 days prior to 2 days after delivery – ZIG to neonat es in the firs t 30 days if mo ther no – Household contacts of those with impaired history or negative serology immunity – Premature infants <28 weeks Healthcare workers – IC where vaccine may be contraindicated – If vaccinated watch for rash for 3 weeks Dose – If unvaccinated or uncertain history (vaccine) – 0- 10 kg 200IU – If does not want vaccination (reassign or place on – 11-30 kg 400 IU sick leave from D 10-21) – > 30 kg 600 IU

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VARICELLA IMMUNOCOMPROMISED CMV

DNA virus First described in 1881(Ribbert) Initially in salivary glands (Salivary gland virus) 60-70% seroprevalence

CMV CMV TRANSMISSION

CMV acquisition Direct person to person spread – Exposure in the home Intimate contact with secretions –SES Excretion starts 4-6 weeks following – Daycare exposure – Prevalence rates of 20-50% in daycare infection No seasonal variation May persist for years Most common cause of congenital infection

CMV TRANSPLANT CMV CLINICAL

Primary, reinfection, reactivation >90% asymptomatic Organomegaly Fever and malaise up to 4 Immunocompromised weeks D+/R- – Fever Headache –Leucopenia CMV pneumonitis BMT > renal> liver Myalgias – Transaminitis patients Abdominal pain – Pneumonitis Diarrhoea – Enterocolitis Prophylaxis Rash – Retinitis CMV pneumonia – Encephalitis –IC – 1-4 months post transplant

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CMV POST TRANSPLANT CMV DIAGNOSIS

Serology Biopsy CMV IgG persists for life – Tissue culture Caution in IC PCR IgM interpretation Remove RF CMV antigenaemia CMV IgM 6 weeks and may Regular monitoring in persist for months Avidity IC

CMV TREATMENT CMV pregnancy

Medications Prevention • What are the – Ganciclovir – CMV - blood options? –Valganciclovir – Hyperimmune globulin – Cidofovir – Prophylactic anti-virals –Foscarnet –Hygiene IC – Leucocyte depleted – Induction (IV) and blood maintenance – ? Vaccine Immunoglobulin CMV Hyperimmune globulin – Viral surveillance

CMV PREGNANCY CASE 7 John

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

Nigro et al 2008 – In his throat…

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CASE 7 John EBV

•7 years old Pfeiffer 1889 – Blood film “ Drusenfeiber” Glandular fever Initially suggestive of leukaemia 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)

EBV EBM TRANSMISSION

DNA virus Kissing disease EBV 1 and 2 EBV not transmitted efficiently Lyypygtic infection in oropharyngeal cells Incubation period 30-50 days Infects B cells Established latency in B cells (1-50 /1,000,000)

EBV CLINICAL

HLH EBV DIAGNOSIS Acute Phase – 1939 – Fever 1-2 weeks – Fever –Sore throat –Pancytopenia FBE + Film Serology – Lymphadenopathy (W 2-4) – Splenomegaly – Lymphocytosis –IgM VCA – Tonsillopharyngitis (W 1) – Haemophagocytosis – Atypical Lymphocytes –XLPD –IgG VCA – Splenomegaly (50%) – Low plts Malignancy – EA antibodies – Hepatomegaly (60%) Heterophile abs –Rash –BL-African and PNG –EBNA later – Jaw>abdominal Resolution phase – Agglutination of –HD sheep/horse RBCs –3-4 wks Complications – Rapid test (Monospot) – Enlarged nodes 3-4 M –Rare – Severe fatigue – Neurological (1-5%) – False positive and – CFS no clear association – ITP (20-50%) negatives – Neutropenia – Cardiac – Respiratory (AO 1-5%) – Neck abscesses

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EBV serology EBV TREATMENT

Supportive Anti-virals: acyclovir,penciclovir, GCV Decrease viral shedding Rituximab (anti-CD20) Chemotherapy

CASE 8 Olivia RSV

5 month old baby Most important respiratory Spreads efficiently (older sib pathogen likely to infect young) Unwell x 2-3 days 91,000 admissions US RVS remains infectious on Poor feeding Infects nearly all children in counter tops for 6 hours RiRespiratory distress the first few years Direct contact First discovered in chimpanzees CXR RNA virus Passive protection Peak 2-5/12 M>F severity

RSV RSV

Incubation period 4-6 Pulse oximetry may prolong Diagnosis Treatment days admission – Clinical – Supportive CXR rarely needed for diagnosis 1% of primary infections – IFA from respiratory –02 Handwashing lead to hospitalisation specimen (nasal swab or – Bronchodilators NPA) controversial Rhinitis, Fever, rales, Apnoea – Serology not helpful in – Steroids not useful wheezes, hypoxaemia, – 20% of hospitalised infants acute setting – Ribavirin apnoea – < 44 weeks Duration 7-12 days Full recovery may take weeks

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RSV PREVENTION Human Metapneumovirus

Breast feeding First described in 2001 Illness similar to RSV RSV immunoglobulin Affects children < 2 years – < 24/12 * gestational age < 36 weeks Most children seropos iiitive by age 5 yrs –Pre-term with CLD No specific treatment – Administered during RSV season Diagnosis by PCR –Expensive No IF test available – No vaccine

CASE 9 JAMES ENTEROVIRUS

4 yrs old Sore throat, fever Humans only natural hosts Blisters on palms and soles of feet Spread by F-O route Rash on palms and Vesicular lesions on buccal Incubation 3-6 days sole of feet surfaces Symptomatic management NlilNeurological Fever – Aseptic meningitis Other Coxsackie viruses – Encephalitis – A 1-24 –CSF findings variable ..you get a brief look –B1 -6 – Early neutrophil Echovirus 1-34 predominance in his mouth Enterovirus 68-71 – Possible sequelae 1-3 – Pleconoril no longer used

CASE 10 EVA Background

2/5/2008 Birth Hx 3/12 girl presenting with cough – Born Tanzania – Nil Antenatal concerns – routine Ix NAD – 42/40 NVD HOPC – BW 3.285g 2/52: – Staccato like cough Social/FHx: – Poor oral intake Tanzanian mother – dental nurse – Gagging and vomiting post cough –Coryza Mother HIV negative at 6/12 pregnancy Australian father – engineer Arrived in Australia 2/52 prior for holiday

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Background Examination Findings

On presentation PHx: Sats 85% RA Breast Feeding with appropriate weight gain to date. BP 85/60, RR 70, PR 160 Nil developmental concerns Moderate respiratory distress

IUTD – inc BCG Meds – Nil regular NKDA

Additional findings on Differential Diagnosis examination oral thrush Infective splenomegaly – Viral – RSV, CMV or other viral infection – Atypical pneumonia - Chlamydia / mycoplasma hepatomegaly – Congenital or miliary TB small BCG scar, no other rashes – Bacterial pneumonia – HIV +/-PCP

Ix Structural • FBE – Hb 118, Plat 196, WCC 11.5, N3.2, L7.2 – Tracheomalacia •CXR –H type TOF Infiltration – Leukaemia

Investigations Further Ix

•FBE: HIV antibodies – positive (WB, ELISA) – Hb 104, Plat 189, WCC 4.7 neuts 2.72 NPA – PCP PCR + lyypmphoc ytes 1.83 HIV tests organised on parents (discordant results) •LFTS: albumin 19 U/S - Enlarged spleen with multiple scattered •U&E –N hypoechoic lesions. ?infective ? Infiltrative ? TB ? • NPA – RSV + (DIF) Fungal

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Global view of HIV Further Investigations

HIV HIV RNA PCR - >750,000 copies/ml CD4 13% (absolute 237) (23-60) CD8 47% (14-25)

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

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

Western & Eastern Europe Central Europe & Central Asia • Vertical transmission North America <100 3700 <<100 [[<100 – <200]] [1700 –6000] East Asia • 25-30% die by 1 yr [<100 – <200] 3200 Middle East & North [2100 – 4500] • <1% infection rate in Caribbean Africa 2300 4600 South & South-East developed countries [1400 – 3400] [2300 – 7500] Asia Sub-Saharan Africa 18 000 • ART effective if can access Latin America 390 000 [11 000 – 25 000] • More resources 6900 [210 000 – 570 000] Oceania [4200 –9700] <500 • Diagnosis often too late [<500 – <1000]

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

HIV virion HIV life cycle

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Transmission – When? What are the chances?...... 100 infants born to HIV-infected women who 60 to 75 infants breastfeed, without any interventions will not be HIV-infected

5–10 About 15 5–15 infected infected infected during during during pregnancy labour and breast- delivery feeding

25 to 40 will be HIV-infected

Courtesy Deepak Patel Courtesy Deepak Patel

Risk factors for vertical Vertical Transmission infection • Accounts for >90% paediatric HIV – Risk if HIV positive mother Advanced maternal disease/low CD4 • Europe ~14%, Africa ~30% High viral load • In utero - from 1st trimester NVD (vs LUSCS) when detectable VL • Intrapartum – 50-70% vertical ROM > 4 hours transmission – Contact with infected secretion or blood Monitoring -FS • Postpartum – 14-29%* Bloody delivery – Breastfeeding Breast feeding

What can we do? Vertical TransmissionTransmission-- Antiretroviral treatment: Maximise maternal status ACTG 076 – Health, nutrition – Maternal zidovudine (ZDV) po from 34/40 Diminish viral load, raise CD4 % – ZDV IV during labour – Maximise anti-retroviral regimen by – Oral ZDV to infant for 1st 6 weeks delivery – Reduced risk from 25.5% to 8.3% Don’t breast feed Maternal HAART (3 drugs) – Risk of transmission 1:1000

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ART

Reverse transcriptase inhibitors Increasing number of HIV Nucleoside analogues (NRTIs) infected women Nucleotide analogues (NRTIs-Tenofovir,abacavir) delivering in Victoria Currently in past two years Non nucleoside RTIs (NNRTIs) ~ 60 women ID Physician GP Interfere with binding at the active site of the RT

Service development in Obstetrician Paediatrician MMC Protease inhibitors (PIs) Melbourne- RWH Dr Michelle Giles (ID) RCH Nurse Pharmacist Dr Olga Vugovic (ID) specialists Dr Tom Connell (PID) Louise Bordun Dr Penelope Bryant (PID) Prof Richard Doherty (PID) Prevention of Infection Jane Howard Karen Blyth

Probability of Death/AIDS within 12 months by VL Probability of Death/AIDS within 12 months by CD4 and age

Courtesy Hermione Lyall Courtesy Hermione Lyall

HIV viral cycle NOVEL AGENTS

NNRTIs Co‐receptor Fusion – TMC125 (Etravirine) Maraviroc inhibitor Enfuvirtide (T20) Protease inhibitors antagonist Vicriviroc – TMC 114 (Darunavir) Zidovudine Maturation inhibitors Stavudine Didanosine – PA-457 NRTI Lamivudine CCR5 antagonists Abacavir – Maraviroc, Vicriviroc NNRTI Nevirapine EfavirenzTenofovir Fusion inhibitors Emtricitabine Lopinavir Etravirine Ritonavir – T651 Integrase Raltegravir Atazanavir Integrase inhbitors inhibitor – MK0518, GS9137 Elvitegravir Darunavir Indinavir Protease Nelfinavir inhibitor Saquinavir Tipranavir

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ART

WHO 2008

Meds do not taste nice!

Vertical TransmissionTransmission-- management of newborn: INFLUENZA Diagnostic PCR: –1st within 48 hrs pick up 38% “last greatest plague of man” –2nd at 2-4 weeks pick up 93% Epidemic 412 BC rd –3 at 4 months pppick up 99.7% 300, 000 hospitalisations annually serology at 12-18 months 8 influenza pandemics since 1580 1918 (20 M deaths worldwide) Orthomyxovirus

INFLUENZA INFLUENZA

RNA virus Droplet spread Surface glycoproteins Haemagluttinin Incubation 1-7 days (HA) Viral shedding shorter for Influenza A Neuraminadase (NA) Humoral and cell mediated immunity Anti HA - neutralisation Anti-NA- decrease severity Secretory IgA

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INFLUENZA CLINICAL H1N1 swine flu

Clinical Complications • 40000 confirmed cases –Abrupt onset – Bacterial infections – Fever 2-3 days – Myositis • Very infectious – Chills – Encephalopathy –Headache – Reye syndrome • High risk in pregnant women –Myalgia – Cardiac Pneumonia – Sudden death • 200 deaths GIT Treatment • Vaccine – Abdominal pain Amantadine (A) – Anorexia Inhaled zanamivir (A/B) Oseltamavir (A/B)

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