RESPIRATORY VIRUSES IN PEDIATRIC AGE

Susanna EspositoPediatric Highly Intensive Care Unit

Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano

Milan, Italy

AGENDA

• Morbillo

• Influenza

• Other emerging viruses

• Genetics and viral infections

• New vaccines

Measles Case Distribution by Month and WHO Regions, 2008-2014

This is surveillance data, hence for the last month, the data may be incomplete. SEAR India is not included in this graph.As of 27 May 2013, South Sudan has reassigned to the Africa region (AFR) from the Eastern Mediterranean region (EMR).Data source: surveillance DEF file

Data in HQ as of 4 August 2014

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

gen2008

Apr Jul Oct gen2009

Apr Jul Oct gen2010

Apr Jul Oct gen2011

Apr Jul Oct gen2012

Apr Jul Oct gen2013

Apr Jul Oct gen2014

Apr

AFR SEAR AMR EMR EUR WPR

Number of Reported Measles Cases with onset date from Jan 2014 to Jun 2014 (6M period)

Data source: surveillance DEF fileData in HQ as of 4 August 2014

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. ©WHO 2014. All rights reserved.

0 (64 countries or 33%)1 - 9 (24 countries or 12%)

10 - 99 (32 countries or 16%)

100 - 999 (40 countries or 21%)

≥1000 (15 countries or 8%)No data reported to WHO HQ

(19 countries or 10%)

Not applicable

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ECDC measles monitoring 2013

ECDC measles monitoring 2013

Population immunity

Epidemiology and genotype data

Surveillance performance

Sustainability of immunization programme

Supplementary evidence

WHO requests - Status by country…

8

Status of measles and rubella elimination

39established National Verification Committee 14 pending

35 Annual Status Reports (2010-2012)

MEASLES 16 interrupted transmission RUBELLA 19 interrupted transmission

Armenia, Azerbaijan, Belarus, Bulgaria, Cyprus, Czech Republic, Estonia, Finland, Israel, Kyrgyzstan, Latvia, Luxembourg, Netherlands, Norway, Portugal, Slovakia

Armenia, Azerbaijan, Belarus, Bulgaria, Croatia, Cyprus, Czech Republic, Estonia, Finland, Ireland, Israel, Kyrgyzstan, Latvia, Luxembourg, Netherlands, Norway, Republic of Moldova, Portugal, Slovakia

10

Data challenges

quality

completenessconsistency

Completeness of reports

Component (%)NVC statement 33 (100%)Immunization coverage (2010-12 + historic) 25 (76%)*Measles incidence 33 (100%)Rubella incidence 32 (97%)Lab performance 33 (100%)Genotype information 22 (67%)Sustainability of NIP 33 (100%)Public acceptance 24 (73%)

* Various methods

Available at: http://www.who.int/influenza/human_animal_interface/Influenza_Summary_IRA_HA_interface_03July13.pdf

H7N9 infections in people and poultry in China in April-MaySporadic infections in humans; many with poultry exposureNo sustained or community transmission

H7N9 OUTBREAK CHARACTERIZATION

Distribution of Respiratory Viruses during the Winter Season 2003–2004

0

5

10

15

20

25

30

45 46 47 48 49 50 51 52 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Influenza RSV hMPV Coronaviruses Rhinovirus Adenovirus

Weeks2003 2004

N=2060 children aged under 15 years

Esposito S, et al. J Med Virol 2006;78:1609–15 and author’s own data.

Perc

enta

ge o

f cas

es

Effect of Age on Healthcare Burden

<6 months 6–12 months 1–<3 years 3 –<5 years 5 –<15 years

Exce

ss e

vent

s pe

r 100

chi

ldre

nOutpatient visits16

14

12

10

8

6

4

2

0

Courses of antibiotics

Excess treatment events in otherwise healthy children under 15 years of age; data over 19 consecutive seasons (US)

Neuzil KM, et al. N Engl J Med 2000;342:225–31. Age

Hospitalisation during Influenza Season according to Age and Presence of Underlying Chronic Disease

YEARS AGEHOSPIT./

100,000 HR SUBJECTS

HOSPIT./100,000 HEALTHY

SUBJECTS

1973 − 19930 − 11 mos

12 − 24 mos3 – 4 yrs

5 – 14 yrs

190080032092

496 – 10381868641

1992 – 19970 − 23 mos

2 – 4 yrs5 – 17 yrs

−−−

144 – 1870 – 258 – 12

1968 − 197315 – 44 yrs45 – 64 yrs≥65 yrs

56 – 110392 – 635399 – 518

23 – 2513 – 23

−1969 – 1995 < 65 yrs

≥65 yrs−−

20 – 42 (*)125 − 228 (*)

(*) without a separation between high-risk (HR) and healthy subjects.Izurieta HS, et al. N Engl J Med 2000;342:232–9.

0

5

10

15

20

25

<6 months

6–11months

1 year

2 years

3 years

4 years

5–10 years

11–17years

00.10.20.30.40.50.60.70.80.91.0

Influenza-Associated Deaths among Children in the United States 2003–2004

Distribution of cases and mortality rates by age group among 153 children with fatal influenza, USA, 2003–2004 season.

Age group

Chi

ldre

n w

ith fa

tal i

nflu

enza

(%)

Deaths per 100,000 children

Fatal influenza cases Mortality rate

Bhat N, et al. N Engl J Med 2005;353:2559–67.

Role of Children in the Transmission of Influenza inHouseholds and Schools

Children are the major pathway of

influenza transmission within communities and

households2

SchoolHousehold &

family members

Influenza attack rates are highest in children, average rate 20.3% (7.5–25.8%)1

Influenza virustransmission

1. Molinari NAM, et al. Vaccine 2007; 25:5086–96.2. Weycker D, et al. Vaccine 2005;23:1284–93.

Influenza B Virus Circulation from 2001 to 2011 Influenza Seasons in the USA and Europe

USA Europe

Ambrose CS, et al. Human Vaccin Immunother 2012;8:81−8.

Influenza B Circulation by Lineages in the USA and Europe between 2001 and 2011

USA

23

100

7

74

19

77

217

8494

7793

2,8

81

23

9883

166

0102030405060708090

100

% In

fluen

za B

str

ains

by

linea

ge

Influenza season and vaccine lineage

EuropeRecommended-Lineage Influenza B Opposite-Lineage Influenza B

Data notavailable

Ambrose CS, et al. Human Vaccin Immunother 2012;8:81−8.

Evolution of Two Antigenically Distinct Lineages of Influenza B (1970-2006)

The pattern of varying dominance of the two influenza B lineages is likely driven by lineage-specific immunity in the population

One lineage predominates until accumulated immunity to that lineage results in increased relative susceptibility to and spread of the other lineage

Chen R, et al. J Mol Evol 2008;66:655−63.

Influenza B Strains: is there a Need of a Quadrivalent Influenza Vaccine?

In 5/10 influenza seasons between 2001–2002 and 2010–2011, the predominant circulating influenza B lineage was different from that chosen for the vaccine

Influenza vaccination campaigns have had limited effectiveness against influenza B epidemics during seasons in which a significant proportion of the disease was caused by opposite-lineage influenza B strains

This reduced effectiveness in such seasons could be avoided if seasonal influenza vaccines included four strains, one strain from each B lineage in addition to A/H1N1 and A/H3N2 strains

It is recommended that vaccines for use in the 2013-2014 influenza season (northern hemisphere winter) contain the following: – an A/California/7/2009 (H1N1)pdm09-like virus – an A(H3N2) virus antigenically like the cell-propagated prototype virus A/Victoria/361/2011 – a B/Massachusetts/2/2012-like virus

It is recommended that quadrivalent vaccines containing two influenza B viruses contain the above three viruses and - a B/Brisbane/60/2008-like virus

2013-2014 WHO RECOMMENDATION FOR INFLUENZA VACCINE COMPOSITION

IMMUNE RESPONSE OF CHILDREN >3 YEARSTO QUADRIVALENT INFLUENZA VACCINE

(From Domachowske JB et al., J Infect Dis 2013)

Jain et al., N Engl J Med 2013

UNIVERSAL INFLUENZA VACCINATION STRATEGIES

M2e-based vaccines

Hemagglutinin-based vaccines

Neuraminidase-based vaccines

T Cell-based vaccines

Ebola Outbreaks

1976- First Major Outbreak (ZEBOV)

1976- Sudan (SEBOV)

Occur Sporadically www.cdc.gov for more

information

Diagnosis of Ebola

Timeline of Infection Diagnostic tests available

Within a few days after symptoms begin

•Antigen‐capture enzyme‐linked immunosorbent assay (ELISA) testing•IgM ELISA•Polymerase chain reaction (PCR)•Virus isolation

Later in disease course or after recovery •IgM and IgG antibodies

Retrospectively in deceased patients•Immunohistochemistry testing•PCR•Virus isolation

• Diagnosing Ebola can be difficult at first since early symptoms, such as fever, are nonspecific to Ebola infection.

• However, if a person has the early symptoms and has had contact with Ebola they should be isolated and public health professionals notified.

• Samples from the patient can then be collected and tested to confirm infection.

Source:  Centers for Disease Control and Prevention http://www.cdc.gov/vhf/ebola/diagnosis/index.html Accessed Oct. 14, 2014

Source: http://www.cdc.gov/vhf/ebola/pdf/checklist‐patients‐evaluated‐us‐evd.pdf Accessed Oct. 14, 2014

Source: http://www.cdc.gov/vhf/ebola/pdf/ppe‐poster.pdf Accessed Oct. 14, 2014

For more detail on PPE for Health Care Workers, please visit:  http://www.cdc.gov/vhf/ebola/hcp/infection‐prevention‐and‐control‐recommendations.html

Hospital Preparedness Checklist

Source:  Centers for Disease Control and Prevention;.  Accessed October 15, 2014http://www.cdc.gov/vhf/ebola/pdf/hospital‐checklist‐ebola‐preparedness.pdf

• Every hospital should ensure that it can detect a patient with Ebola, protect health care workers, and respond in a coordinated fashion. 

• Many signs and symptoms of Ebola are non‐specific and similar to common diseases. 

• Transmission can be prevented with appropriate infection control measures. 

• Checklist highlights key areas for hospital emergency management officers, infection control practitioners, and clinicians to detect possible Ebola cases, protect employees, and respond appropriately.

• Hospitals should review infection control procedures and incorporate plans for administrative, environmental, and communication measures, as well as personal protective equipment (PPE) training and education. 

• Hospitals should also define the individual work practices that will be required to detect the introduction of a patient with Ebola, prevent spread, and manage the impact on patients, the hospital, and staff.  

CHARACTERI-SATION OF

NOVELENTEROVIRUSES

(From Piralla A et al., PLoS One 2013)

MERS-CoV

• Middle East Respiratory Syndrome-Coronavirus• Formerly called novel coronavirus

• Not the same coronovirus that caused SARS• Newly identified virus, causes severe acute respiratory

illness – first seen in April 2012• 54 cases, including 30 deaths (55.6%) to date• 8 countries, with 72% in Saudi Arabia• No cases in U.S.• Can spread from person to person during close contact

• Families• Healthcare

Countries Cases (Deaths)

France 2 (1)

Italy 3 (0)

Jordan 2 (2)

Qatar 2 (0)

Saudi Arabia 39 (24)

Tunisia 2 (0)

United Kingdom (UK) 3 (2)

United Arab Emirates (UAE) 1 (1)

Total 54 (30)

MERS Cases and Deaths, April 2012 - June 2013 Current as of June 4, 2013

Euro Surveill. 2013 Aug 22;18(34). pii: 20564.Investigation of an imported case of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in Florence, Italy, May to June 2013.Puzelli S, Azzi A, Santini M, Di Martino A, Facchini M, Castrucci M, Meola M, Arvia R, Corcioli F, Pierucci F, Baretti S, Bartoloni A, Bartolozzi D, de Martino M, Galli L, Pompa M, Rezza G, Balocchini E, Donatelli I.

CORONAVIRUS HKU1 IDENTIFIED IN AN ITALIAN INFANT WITH

BRONCHIOLITIS

N P It a ly H K U 1 A Y 5 9 7 0 1 1 H K U 1 N C 0 0 6 5 7 7 O C 4 3

S A R S N L 6 3 A m s te r d a m

2 2 9 E1 0 0

1 0 0

1 0 0

0 .0 5

H K U 1 A Y 5 9 7 0 1 1 H K U 1 N C 0 0 6 5 7 7 S g e n e It a ly

O C 4 3 S A R S

N L 6 3 A m s t e r d a m 2 2 9 E1 0 0

1 0 0

7 41 0 0

0 . 1

Bosis S et al. J Clin Virol 2006

THE RESPECTIVE CONTRIBUTIONS OF HOST AND MICROBE GENETICS ON THE CLINICAL OUTCOME OF

INFECTIOUS DISEASES(From Casanova JL and Abel L. Ann Rev Genomics Hum Genet 2013)

A PROPOSED AGE-DEPENDENT GENETICARCHITECTURE OF INFECTIOUS DISEASES

(From Casanova JL and Abel L. Ann Rev Genomics Hum Genet 2013)

MAIN STUDIES DEMONSTRATING ASSOCIATION BETWEEN TLR4 POLYMORPHISMS AND INFECTIOUS DISEASES

GENETIC POLYMORPHISMS AND RISK OF INFECTIOUS WHEEZING IN

PEDIATRIC AGE(Esposito et al., BMC Infect Dis 2014)

This study has been planned to evaluate whethermodifications of some genes involved in the regulationof innate or adaptive immunity can favor repeated

viral infections that induce persistent airwaymodifications and chronic severe respiratory disease

Demographic and clinical characteristics of the studypopulation at the time of the first wheezing episode

Characteristics Control group

(n=119)

Childrenwith

wheezing(n=119)

P-value

Childrenwith non-recurrentwheezing(=45)

Childrenwith

recurrentwheezing(n=74)

P-value

Females, n (%) 43 (36.1) 43 (36.1) 1.00 16 (35.6) 27 (36.5) 0.92

Median age (range), months 6 (0.3-12) 6 (0.3-12) 1.00 6 (0.3-12) 6 (0.3-12) 1.00

Caucasian, n (%) 113 (95.0) 113 (95.0) 1.00 42 (93.3) 71 (95.5) 0.67

Median gestational age (range), weeks

38.3 (37-41) 38.1 (37-41) 0.97 38.2 (37-41)

37.6 (37-40) 0.94

Subjects breastfed ≥3 months, n (%)

82 (68.9) 73 (61.3) 0.27 29 (64.4) 44 (59.5) 0.72

Subjects regularly using pacifier, n (%)

30 (25.2) 31 (26.1) 1.00 10 (22.2) 21 (28.4) 0.59

Subjects with at least one oldersibling, n (%)

28 (23.5) 33 (27.7) 0.55 12 (26.7) 21 (28.4) 0.99

Subjects exposed to cigarettesmoke, n (%)

55 (46.2) 79 (66.4) 0.002 26 (57.8) 53 (71.6) 0.17

Subjects with high IgE level, n (%)

11 (9.2) 76 (63.9) <0.001 24 (53.3) 52 (70.3) 0.09

Subjects with family history of atopy, n (%)

24 (20.2) 85 (71.4) <0.001 24 (53.3) 61 (82.4) 0.001

Genotype frequencies of selected SNPs in controlsand in children with wheezing (I)

Gene and polymorphic alleles

Control group

(n=119)

N %

Childrenwith

wheezing(n=119)N %

Control group

(n=119)

N %

Childrenwith

wheezing(n= 119)

N %

HWE, Χ2

ControlsP-value

HWE, Χ2

WheezingP-value

ORb 95% CI P-value

IL8‐rs4073AA/TT

28        23.747        39.843        36.4

21        17.857        48.340        33.9

22.5        19.058.0        49.237.5        31.8

20.8           17.657.5           48.739.8           33.7 0.04 0.93

1.002.501.57

(reference)(1.15‐5.44)(0.71‐3.45)

‐0.020.27

VEGFA‐rs833058CC/TT 

32 27.160 50.926        22.0

22 18.572 60.5 25        21.0

32.6         27.658.8         49.926.6         22.5

28.3           23.859.5           50.031.3           26.3 0.83 0.02

1.002.221.96

(reference)(1.09‐4.55)(0.83‐4.65)

‐0.03O.13

MBL2‐rs1800450CC/TT

87 73.729 24.62             1.7

76 63.940 33.63            2.5

87.3         74.028.4         24.12.3             2.0

77.4           65.137.1           31.24.4               3.7 0.81 0.40

1.001.901.03

(reference)(1.01‐3.58)(0.15‐7.239

‐0.050.97

IKBKB‐rs3747811AA/TT

36 31.342 36.537        32.2

20 17.167 57.330        25.6

28.3         24.657.5         50.029.3         25.4 

24.5           20.958.1           49.634.5           29.5 0.004 0.10

1.003.262.01

(reference)(1.55‐6.85)(0.89‐4.53)

‐0.00180.09

Genotype frequencies of selected SNPs in controlsand in children with bronchospasm (II)

Gene and polymorphicalleles

Control group

(n=119)

N %

Childrenwith

wheezing(n=119)N %

Control group

(n=119)

N %

Childrenwith

wheezing(n= 119)

N %

HWE, Χ2

ControlsP-value

HWE, Χ2

WheezingP-value

ORb 95% CI P-value

CTLA4‐rs3087243AA/GG

25        21.273        61.920        17.0

35        29.760        50.923        19.5

32.1        27.258.9        49.927.1        22.9

35.8           30.358.4           49.523.8           20.2 0.009 0.76

1.000.500.65

(reference)(0.25‐0.99)(0.27‐1.56)

‐0.050.34

NFKBIB‐rs3136642CC/TT

64        54.240        33.914        11.9

72        61.039        33.1 7           5.9

59.8         50.748.4         41.09.8           8.3

71.0           60.141.1           34.86.0             5.0 0.06 0.58

1.000.900.33

(reference)(0.49‐0.66)(0.11‐0.94)

‐0.730.04

Genotype frequencies of selected SNPs with significant differences in children with recurrent

or non-recurrent wheezingGene and

polymorphic alleles

Non-recurrent (n=74)

N %

Recurrentwheezing(n=119)

N %

Non recurrent(n=74)

N %

Recurrentwheezing(n= 119)

N %

HWE, Χ2

ControlsP-value

HWE, Χ2

WheezingP-value

ORb 95% CI P-value

IL8‐rs4073AA/TT

17        23.326        35.630        41.1

4             8.931          68.910          22.2

12.3        16.935.3        48.425.3        34.7

8.5            18.822.1            49.115.5            32.1 0.02 0.007

1.003.601.18

(reference)(1.03‐12.57)

(0.31‐4.51)

‐0.040.81

VEGFA‐rs2146323AA/CC 

4           5.437         50.033         44.6

8          17.819          42.2 18          40.0

6.8           9.231.3         42.335.8         48.4

6.8             15.121.4             47.516.8             37.3 0.12 0.45

4.321.081.96

(1.06‐17.64)

(0.46‐2.54)(reference)

0.040.85‐

TLR3‐rs3775291TT/CC

10         13.731         42.532         43.8

4             8.913           28.928           62.2

8.9         12.233.2         45.130.9         42.3

2.5                5.4 16.1             35.826.5             58.8 0.57 0.20

0.750.361.00

(0.20‐2.75)(0.14‐0.90)(reference)

0.660.031.00

NFKBIA‐rs2233419AA/GG

5           6.814         18.955         74.3

2            4.416          35.627          60.0

1.9             2.620.1         27.251.9         70.2 

2.2               4.915.6             34.627.2             60.5 0.009 0.85

0.822.791.00

(0.13‐5.05)(1.12‐6.99)(reference)

0.830.03‐

Frequency distribution of viral infections in children with recurrent or non-recurrent wheezing

Viral infection N % N % P-valueRSVNoYes

2153

28.471.6

2223

48.951.1 0.02

RV (any type)No Yes

5915

79.720.3

3312

73.326.7 0.42

EnterovirusNoYes

704

94.65.4

378

82.217.8 0.055

Coronavirus (any type)NoYes

713

96.04.0

432

95.64.4 1.00

MetapneumovirusNoYes

686

91.98.1

432

95.64.4 0.71

BocavirusNoYes

722

97.32.7

432

95.64.4 0.63

Influenza (any type)NoYes

722

97.32.7

441

97.82.2 1.00

Parainfluenza (any type)NoYes

722

97.32.7

450

100.00.0 0.53

Any viral infectionNoYes

767

9.590.5

837

17.882.2 0.18

Non-recurrent wheezing (n=74) Recurrent wheezing (n=45)

GENE-ENVIRONMENT INTERACTION

• Rhinovirus significantly associated with recurrent wheezing in the presence of IL4Ra-rs1801275GG and G (OR 6.03, 95% CI: 1.21-30.10, p=0.03) and MAP3K1-rs702689AA (OR 4.09, 95% CI: 1.14-14.61, p=0.03)

• No significant difference observed in the distribution of genetic polymorphisms among the children with RSV or other viral infections and non-recurrent or recurrent wheezing

CONCLUSIONS

• This study shows a relationship between the riskof wheezing and polymorphisms of some of the genes involved in the immune response

• Susceptibility to the development of wheezing seems to be greater in children with SNPs of the IL8 (rs4073AT), VEGFA (rs833058CT), MBL2 (rs1800450CT) and IKBKB genes (rs3747811AT)

• Despite not conclusive, these results indicate thatgenetics play an important role in conditioningwheezing development

• Further studies are needed in order to establishwhich are the real association between wheezingdevelopment and genetic variations

2003 pre-clinical trials 2010

New species of Ebola - Bundibugyo - emerged in 2007 Experimental vaccines being developed against other

lethal Ebola species found to totally protected against it did not stimulate antibodies against the new species protection depended entirely on cellular immunity

"The dogma is that viruses require an antibody response to prevent the virus from entering the cell," Sullivan says. "This is truly the first time that cell-mediated immunity alone has been shown to be protective against virus infection.“

Vaccine Trials in the News… Ebola

Study Design 8 macaques – 4 vaccinated / 4 unvaccinated All inoculated with lethal doses of Ebola Vaccinated animals survived, Unvaccinated animals died

Vaccine pieces of the Zaire & Sudan viruses’ protein-sugar coat

(glycoprotein) inserted into a type of common cold virus The cold virus carries the Ebola glycoprotein into cells of

the vaccine recipients 4 "priming" shots, followed a year later with a booster

“There's no way to do trials of Ebola vaccines in humans. Unlike, say, a vaccine for HIV, there's no identifiable group of people at risk for Ebola...”

Vaccine Trials in the News… Ebola

2009: 3rd largest AIDS vaccine trial to date Cost the US government $105 M Largest done in humans: >16,000 participants

Controversy: Combination of 2 vaccines that each failed

when tested for use individually 2004 editorial in Science signed by 22 top

AIDS researchers: Suggested trial was a waste of $$

Vaccine Trials in the News… HIV

NPR: AIDS Vaccine Prevents Some HIV Infections

HIV Vaccine

Vaccines Tested: Sanofi-Aventis Alvac-HIV

Carrier vaccine Canarypox virus with 3 AIDS virus genes grafted

onto it Stimulate cell mediated immunity

Genentech Aidsvax Non-infectious sub-unit vaccine Contains two recombinant gp120 proteins found

on surface of different strains of HIV virus Stimulate anti-body mediated immunity

Dangers of Vaccine Trials

Most researchers feel first HIV vaccines will not be more than 40-50% effective Will vaccinated individuals engage in higher

risk behaviors? Vaccine could cause as much harm as it

prevents http://www.npr.org/templates/story/story.php?s

toryId=113177004

Future vaccines cannot be tested against placebo, would be unethical

RSV AS CAUSE OF ACUTE

RESPIRATORYILLNESS AND BRONCHIO-LITIS IN HOSPITAL

AND EMERGENCY

DEPARTMENTS

(From Borchers AT et al., Clin Rev Allergol

Immunol 2013)

TESTED APPROACHES FOR THE PRODUCTION OF RSV VACCINES

Production of live attenuated cold-passaged and temperature sensitive mutants

Creation of recombinant RSV virus with deletionsof one or more virus proteins or expressing hostcytokines in order to boost vaccine response

Vectored vaccines Use of adjuvants, including TLR9 and NOD2 ligands

REVIEW OF STUDIES EXAMINING PREVALENCEOF NOROVIRUS AMONG OUTBREAKS OF

GASTROENTERITIS FROM ALL ETIOLOGIES(From Patel MM et al., J Clin Virol 2009)

EFFICACY OF AN INTRANASALLY DELIVEREDNOROVIRUS VIRUS-LIKE PARTICLE VACCINE (I)

(From Atmar RL at al., N Engl J Med 2011)

EFFICACY OF AN INTRANASALLY DELIVEREDNOROVIRUS VIRUS-LIKE PARTICLE VACCINE

(II)(From Atmar RL at al., N Engl J Med 2011)

CONCLUSIONS• Viral infectious diseases have an important burden

on childhood health

• Old and new viruses have a significant role ascause of disease

• Genetics seem to have an important role in conditioning susceptibility and/or severity to specific infections

• Interesting new vaccines are in development

BOARDSusanna Esposito (Milan, Italy), President

Francesco Blasi (Milan, Italy)Kathryn Edwards (Vanderbilt, USA)

Ivan Hung (Hong Kong, China)Irja Lutsar (Tallin, Estonia)

Shabir Madhi (Johannesburg, South Africa)Miguel O’Ryan (Santiago, Chile)

Albert Osterhaus (Rotterdam, The Netherlands)Yehuda Shoenfeld (Tel-Hashomer, Israel)

Tina Tan (Chicago, USA)www.waidid.org