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I “NUOVI” PATOGENI RESPIRATORI Susanna Esposito Istituto di Pediatria, Università di Milano Fondazione IRCCS “Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena” Milano

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I “NUOVI” PATOGENI RESPIRATORI. Susanna Esposito Istituto di Pediatria, Università di Milano Fondazione IRCCS “Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena” Milano. NEWER RESPIRATORY VIRUS INFECTIONS. - PowerPoint PPT Presentation

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Page 1: I “NUOVI” PATOGENI RESPIRATORI

I “NUOVI” PATOGENI RESPIRATORI

Susanna EspositoIstituto di Pediatria, Università di MilanoFondazione IRCCS “Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena”

Milano

Page 2: I “NUOVI” PATOGENI RESPIRATORI

NEWER RESPIRATORY VIRUS INFECTIONS

• Acute respiratory tract infections are responsible for considerable morbidity and mortality

• A variety of viruses are associated with RTIs

• Since the beginning of the millenium, the Paramyxoviridae, the Coronaviridae and Parvoviridae virus families have been expanded

• In the past five years, we have also become reacquainted with several influenza A virus subtypes that crossed the species barrier

Page 3: I “NUOVI” PATOGENI RESPIRATORI

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

I nfluenza RSV hMPV Coronaviruses Rhinovirus Adenovirus

Weeks

% cases

DISTRIBUTION OF RESPIRATORY VIRUSES DURING THE WINTER SEASON 2003-2004

(Children enrolled = 2,060)Esposito S et al. J Med Virol 2006

2003 2004

Page 4: I “NUOVI” PATOGENI RESPIRATORI

IN JUNE 2001 VAN DEN HOOGEN ET AL. AT THE ERASMUS MEDICAL CENTER, ROTTERDAM,

REPORTED THE DISCOVERY OF A NEW RESPIRATORY PATHOGEN

Van Den Hoogen et al. Nat Med 2001;7:719-24

Page 5: I “NUOVI” PATOGENI RESPIRATORI

hMPV EPIDEMIOLOGY

PHYLOGENETIC ANALYSIS OF STRAINS DEMONTRATED 2 MAIN LINEAGES OF hMPV (A, B) AND 4 SUBLINEAGES (A1, A2, B1,B2)

SEROLOGICAL DATA INDICATED THAT hMPV CAN CAUSE

MULTIPLE INFECTIONS IN HUMAN BEINGS

STUDIES SUGGESTED A SEASONAL DISTRIBUTION

UNDERLYING CONDITIONS MAY PREDISPOSE PATIENTS TO

SEVERE hMPV DISEASE

COINFECTION WITH hMPV MIGHT BE A DETERMINANT OF RSV

DISEASE SEVERITY

Page 6: I “NUOVI” PATOGENI RESPIRATORI

DISTRIBUTION OF HMPV-INFECTIONS IN ITALY

2003-2004

• 49 (2.4%) of the cases were single hMPV infections: hMPV A in 24 (49.0%), hMPV B in 14 (28.6%) and untyped hMPV in 11 (22.4%)

• 11 children (0.5%) were co-infected by hMPV and another respiratory virus

Esposito S et al., 25th ESPID 2007

Page 7: I “NUOVI” PATOGENI RESPIRATORI

CLINICAL PRESENTATION OF THE STUDY CHILDREN WITH HMPV INFECTION WAS

DIAGNOSED (from Principi et al. NEJM 2004)

Page 8: I “NUOVI” PATOGENI RESPIRATORI

IMPACT AMONG HOUSEHOLD CONTACTS OF THE STUDY CHILDREN IN WHOM HMPV

INFECTION WAS DIAGNOSED (from Principi et al NEJM 2004)

Page 9: I “NUOVI” PATOGENI RESPIRATORI

CLINICAL OUTCOME OF THE STUDY CHILDREN IN WHOM HMPV

INFECTION WAS DIAGNOSED

hMPV-A (n=24)

hMPV-B (n=14)

Untyped hMPV (n=11)

hMPV-coinfected

(n=11)

HOSPITALIZATION (%)

4 (16.7) 1 (7.1) 1 (9.1) 1 (9.1)

SCHOOL ABSENCE, MEDIAN DAYS (range)

8 (1-15) 5 (1-10) 5 (1-10) 7 (1-15)

Esposito S et al., 25th ESPID 2007

Page 10: I “NUOVI” PATOGENI RESPIRATORI

PHARMACOLOGICAL TREATMENT IN THE STUDY CHILDREN IN WHOM hMPV INFECTION WAS DIAGNOSED (%)

hMPV-A (n=24)

hMPV-B (n=14)

Untyped hMPV (n=11)

hMPV-coinfected

(n=11)

ANTIPYRETIC PRESCRIPITIONS

15 (62.5) 9 (64.3) 5 (45.5) 9 (81.8)

ANTIBIOTIC PRESCRIPTIONS

12 (50.0) 8 (57.1) 5 (45.5) 6 (54.6)

BRONCHODILATOR PRESCRIPTIONS

5 (20.8) 4 (28.6) 2 (18.2) 2 (18.2)

STEROID PRESCRIPTIONS

3 (12.5) 0 (0.0) 2 (18.2) 1 (9.1)

Esposito S et al., 25th ESPID 2007

Page 11: I “NUOVI” PATOGENI RESPIRATORI

IMPACT AMONG HOUSEHOLD CONTACTS OF THE STUDY CHILDREN IN WHOM HMPV

INFECTION WAS DIAGNOSED

hMPV-A (n=85)

hMPV-B (n=47)

Untyped hMPV (n=39)

hMPV-coinfected

(n=41)

DISEASE SIMILAR TO THAT OF THE INFECTED CHILD (%)

12 (14.1) 4 (8.5) 3 (7.7) 5 (12.2)

ADDITIONAL MEDICAL VISITS (%)

7 (8.2) 5 (10.6) 1 (2.6) 2 (4.9)

ANTIPYRETIC PRESCRIPTIONS (%)

8 (9.4) 4 (8.5)3 (7.7) 5 (12.2)

ANTIBIOTIC PRESCRIPTIONS (%)

2 (2.4) 2 (4.3) 1 (2.6) 2 (4.9)

LOST WORKING DAYS, MEDIAN (range)

3 (1-7) 3 (1-5) 2 (1-4) 3 (1-5)

LOST SCHOOL DAYS, MEDIAN (range)

2 (1-5) 2 (1-3) 2 (1-3) 3 (1-5)

Esposito S et al., 25th ESPID 2007

Page 12: I “NUOVI” PATOGENI RESPIRATORI

VIRAL LOAD (MEAN + SD cp/mL) AND DISEASE SEVERITY IN CHILDREN

WITH HMPV INFECTION

LRTI involvement URTI involvement

p

1,424,270 + 3,401,326

3,276 + 5,545 <0.001

Hospitalized children Outpatient children

p

4,817,875 + 5,467,264

74,177 + 115,661

<0.001

Children who had households with a

similar disease

Children who had not

households with a similar disease

p

1,769,850 + 3,736,830

9,721 + 16,189 <0.001

Esposito S et al., 25th ESPID 2007

Page 13: I “NUOVI” PATOGENI RESPIRATORI

CORONAVIRUS

Nidovirales

Coronaviridae

Coronavirus - Grp I

- Grp II

- Grp III

RNA virus Found everywhereCause of mild as well as severe infections sometimes with epidemic peaks that could involve mainly respiratory and gastroenteric tracts

Page 14: I “NUOVI” PATOGENI RESPIRATORI

CORONAVIRUS HOST AND DISEASES

Disease (site of infection) Genetic group

Virus Host Respiratory Enteric Other

1

HcoV-229E HCoV-NL63 TGEV PRCoV PEDV FIPV FcoV CcoV

Human Human Pig Pig Pig Cat Cat Dog

X X

(X) X

X

X X

X X X X

Sistemic

2

HcoV-OC43 HCoV-HKU1 MHV RcoV HEV BcoV

Human Human Mouse Mouse Pig Bovin

X X X X

X

X X X

X X

CNS, sistemic eye, urinary

tract

3 IBV TCoV

Chicken Turkey

X

X X

Kidney

4?? SARS-CoV Human X (X) (Kidney)

Page 15: I “NUOVI” PATOGENI RESPIRATORI

34

36

38

40

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

Viral Immune response Organ involvementreplication

Days from the beginning of the disease

CORONAVIRUS INFECTIONS: PATHOGENESIS

Page 16: I “NUOVI” PATOGENI RESPIRATORI

EPIDEMIOLOGIC RESULTS

2,060 children < 15 yrs (1,112 males)

Mean age + SD, 3.46 + 3.30 yrs

HCoVs were detected in 79 children (3.8%) as against influenza in 235 (11.4%;

p<0.0001), RSV in 171 (8.3%; p<0.0001), adenovirus in 136 (6.6%; p<0.0001),

rhinoviruses in 130 (6.3%; p<0.05), hMPV in 48 (2.3%; p<0.05) and parainfluenza

viruses in 29 (1.4%; p<0.05)

Esposito S et al. J Med Virol 2006

Page 17: I “NUOVI” PATOGENI RESPIRATORI

DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF CHILDREN WITH CORONAVIRUS INFECTION

Esposito S et al. J Med Virol 2006

Page 18: I “NUOVI” PATOGENI RESPIRATORI

DIAGNOSIS, THERAPY AND CLINICAL OUTCOME IN CHILDREN

WITH BOCAVIRUS INFECTION

Esposito S et al. J Med Virol 2006

Page 19: I “NUOVI” PATOGENI RESPIRATORI

RES PI RA T O RY I N FECT I O N S I N H O US EH O LDS CO N T A CT S BY VI RA L I N FECT I O N I N T H E

S T UDY PO PU LA T I O NEsposito S et al. J M ed Virol 2006

0

2

4

6

8

10

12%

Page 20: I “NUOVI” PATOGENI RESPIRATORI

SARS in pediatric age

• Under 12 years of age, SARS appears as a moderate disease clinically less aggressive than in adults

• Radiographic alterations appear low and not

severe

• The main signs were cough and nasal

congestion

• No death is observed in the first 12 years of age

Page 21: I “NUOVI” PATOGENI RESPIRATORI

FIRST DETECTION OF CORONAVIRUS HKU1 IN AN ITALIAN INFANT WITH

BRONCHIOLITIS • While studying the epidemiology of viral

respiratory infections in Italy during the winter seasons from 2002-2003 to 2004-2005, we detected HCoV-HKU1 in the nasopharyngeal secretions of a pre-term infant hospitalized for bronchiolitis

• This finding not only allows a better definition of the disease’s possible etiology, but also confirms that coronaviruses can cause mild, as well as moderate/severe respiratory infections

Bosis S et al. J Clin Virol 2007

Page 22: I “NUOVI” PATOGENI RESPIRATORI

HUMAN BOCAVIRUS (hBoV)

• Latest addition to the list of novel respiratory virus

• Described by Allander et al. in Swedish children in 2005

• DNA virus closely related to the Bovine Parvovirus (BPV)

• Classified in the genus Bocavirus within the Parvoviridae

Page 23: I “NUOVI” PATOGENI RESPIRATORI

FREQUENCY OF hBoV INFECTIONS

AUTHORS (YRS) PREVALENCE STUDY POPULATION

Allander et al. (2005) 3.1% Swedish children with LRTIs

Sloots et al. (2006) 5.6% Respiratory samples from Australian adults

and children

Ma et al. (2006) 5.7% Japanese children with LRTI

Bastien et al. (2006) 1.5% Respiratory samples from Canadian adults

and children

Foulongne et al. (2006)

3.4% Respiratory samples from French children <5

yrs

Weissbrick et al. (2006)

10.3% Respiratory samples from German children

<8 yrs

Page 24: I “NUOVI” PATOGENI RESPIRATORI

SYMPTOMS OF PATIENTS WITH hBoV INFECTIONS

Arnold et al., CID 2006

Page 25: I “NUOVI” PATOGENI RESPIRATORI

FREQUENCY OF DETECTION OF RESPIRATORY VIRUSES AMONG 1,332

CHILDREN ATTENDING THE EMERGENCY ROOM

0

2

4

6

8

10

12

14

16

Influenza RSV Adenovirus Rhinovirua Bocavirus Coronavirus PIV HMPV

%

Esposito S et al., J Clin Microbiol 2008

Page 26: I “NUOVI” PATOGENI RESPIRATORI

AGE DISTRIBUTION OF BOCAVIRUS INFECTIONS

Age (yrs)BOCAVIRUS

(N=99)

<1 17 (17.2%)

1-2 47 (47.4%)

2-5 25 (25.3%)

>5 10 (10.1%)

Esposito S et al., J Clin Microbiol 2008

Page 27: I “NUOVI” PATOGENI RESPIRATORI

FREQUENCY OF HUMAN BOCAVIRUS (HBOV) CO-

DETECTION

Virus detection status HBoV-positive samples, no.

(%)

HBoV-negative

samples, no. (%)

Single infection detected 49 (49.5)* 475 (72.5)

Co-infection detected 50 (50.5)* 180 (27.5)

With a total of 2 viruses 41 (41.4)* 180 (27.5)

With a total of 3 viruses 9 (9.1) 0 (0.0)

Total 99 (100.0) 655 (100.0)

*p< 0.0001; no other significant difference between the groups.

Esposito S et al., J Clin Microbiol 2008

Page 28: I “NUOVI” PATOGENI RESPIRATORI

CLINICAL MANIFESTATIONS IN CHILDREN WITH HUMAN BOCAVIRUS (HBOV)

INFECTIONS

DiagnosisNo virus

(No.=578)Single

bocavirus (No.=49)

Bocavirus co-infection (n=50)

URTI 202 (34.9%) 42 (85.7%)* 21 (42.0)

Pharyngitis 115 (19.9%) 27 (55.1%)* 9 (42.8%)

AOM 64 (11.1%) 9 (18.4%) 7 (14.0%)

Rhinosinusitis 23 (3.3%) 6 (12.2%) 5 (10.0%)

LRTI 50 (8.7%) 2 (4.0%)* 24 (48.0%)

Acute bronchitis

20 (3.5%) 1 (2.0%)* 9 (18.0%)

Wheezing 19 (3.3%) 1 (2.0%) 7 (14.0%)

Pneumonia 11 (1.9%) 0 (0)* 8 (16.0%)

Gastroenteritis 90 (15.6%) 5 (10.2%) 5 (10.0%)

Fever ws 23 (3.9%) 0 (0) 0 (0)

Exanthema 18 (3.1%) 0 (0) 0 (0)

Other diagnosis 195 (33.7%) 0 (0) 0 (0) *p<0.05

Page 29: I “NUOVI” PATOGENI RESPIRATORI

CLINICAL OUTCOME IN CHILDREN WITH HUMAN BOCAVIRUS (HBOV) INFECTIONS

No virus(No.=578)

Single bocavirus (No.=49)

Bocavirus co-infection(n=50)

Examinations

Laboratory tests 186 (32.2%) 13 (26.5%)* 25 (50.0%)

Radiographic examinations

29 (5.0%) 2 (4.1%)* 11 (22.0%)

Outcome

Hospitalization 43 (7.4%) 2 (4.1%)* 10 (20.0%)

Days lost from school

10 (1-20) 10 (1-15) 12 (2-18)

Therapies

Antibiotic 234 (40.5%) 26 (53.1%) 36 (72.0%)

Acetaminophen 297 (51.4%) 30 (61.2%) 39 (78.0%)

NSAID 13 (2.2%) 0 (0) 2 (4.0%)

Aerosol therapy 42 (7.3%) 3 (6.1%)* 15 (30.0%)

Oral steroids 14 (2.4%) 1 (2.0%)* 9 (18.0%)

*p<0.05

Page 30: I “NUOVI” PATOGENI RESPIRATORI

CLINICAL IMPACT AMONG HOUSEHOLDS OF CHILDREN WITH HUMAN BOCAVIRUS

(HBOV) INFECTIONS

Impact among households

No virus(No.=578)

Single bocavirus (No.=49)

Bocavirus co-infection(n=50)

Respiratory tract infections

92/1425 (6.5%)

14/120 (11.7%) 21/126 (16.7%)

Medical visits 48/1425 (3.4%)

9/120 (7.5%) 12/126 (9.5%)

Hospitalization 4/1425 (0.3%)

0 (0) 1/50 (2.0%)

Antibiotics 22/1425 (1.5%)

4/120 (3.3%) 7/126 (5.6%)

Antipyretics 48/1425 (3.4%)

9/120 (7.5%) 12/126 (9.5%)

Page 31: I “NUOVI” PATOGENI RESPIRATORI

TAKE HOME MESSAGES: EMERGING RESPIRATORY

VIRUSES

• Respiratory viral pathogens, old and new, continue to be an important threat to human health

• Diagnostic techniques remain crucial for the rapid identification of known and unknown pathogens

• It will be essential to further increase our understanding of virus epidemiology, pathogenesis, clinical presentation and host defense against infection