i “nuovi” patogeni respiratori
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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 PresentationTRANSCRIPT
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I “NUOVI” PATOGENI RESPIRATORI
Susanna EspositoIstituto di Pediatria, Università di MilanoFondazione IRCCS “Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena”
Milano
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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
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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
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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
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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
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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
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CLINICAL PRESENTATION OF THE STUDY CHILDREN WITH HMPV INFECTION WAS
DIAGNOSED (from Principi et al. NEJM 2004)
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IMPACT AMONG HOUSEHOLD CONTACTS OF THE STUDY CHILDREN IN WHOM HMPV
INFECTION WAS DIAGNOSED (from Principi et al NEJM 2004)
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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
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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
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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
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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
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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
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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)
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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
C°
Days from the beginning of the disease
CORONAVIRUS INFECTIONS: PATHOGENESIS
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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
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DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF CHILDREN WITH CORONAVIRUS INFECTION
Esposito S et al. J Med Virol 2006
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DIAGNOSIS, THERAPY AND CLINICAL OUTCOME IN CHILDREN
WITH BOCAVIRUS INFECTION
Esposito S et al. J Med Virol 2006
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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%
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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
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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
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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
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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
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SYMPTOMS OF PATIENTS WITH hBoV INFECTIONS
Arnold et al., CID 2006
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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
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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
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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
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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
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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
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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%)
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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