Bordetella pertussis In Infants Admitted for Bronchiolitis During Winter to Hospitals In Northern Israel: Epidemiology, Clinical Course and

Transcription

1 , : Bordetella pertussis In Infants Admitted for Bronchiolitis During Winter to Hospitals In Northern Israel: Epidemiology, Clinical Course and Prognosis., ': : : hayanakhleh@yahoo.com: " " ", : - ",, ' : : -, : -",," : -,,',-,' : - " 1

2 2 :. 50% ),(-,.., 1.5:1.[1] 4-6,. 3-7,,,.. :,....[1,2,3], (). :,, % -, - Respiratory Syncytial Virus.(RSV), 76% RSV.[4] 49% 27%. Bordetella pertussis " 6.2% ).( 0.6% 5.6%.

3 : ) Bordetella pertussis ".Bordetella parapertussis " (Bp. -Bp. : 90%, ,(CDC) % ". 6.[5] / , ) 72/100,000,2008,.[6] (,1940.." 15-20,,, :. ) Polymerase Chain Reaction. (PCR 3

4 : ,, : " 6-8 :,,,,,, 1-2 :catarrhal stage.1.[1],/.., 2-4 :paroxysmal stage.2..,,., 1-2 :convalescent stage.3., " 4

5 ,.[7]. " :.. ( ) : :. ", :.. " " :.. Bp,100% (Regan-Lowe),.. 3,.[8] Bp PCR." PCR.. PCR.. - " " :,. insertion sequence IS % :pertussis toxin promoter region (ptxa-pr)., DFA Direct fluorescent antibody.[9] 3- (PT) (Ig) G, 100 IgG anti-pt. Bp 4. EU/mL 5

6 20%-90%,.[10]. : " inspiratory whoop -, :. PCR :. : CDC : whoop, 14. :. - PCR, ;, : PCR.PCR " :. 6

7 7 :, Bp",.. :, [11] : :, ,,.[1], CDC-,,.[12-14] : * * * *, :, * ",).( : * *, * 3.

8 .,,.. (azithromycin,clarithromycin, ). sulfamethoxazole-,( 7) ( 3-5),( 7). Bordetella pertussis : : " *..[7] DTP- () () , 1981 **-.( ) DTaP. :(whole-cell) * :,,. 24.,. (). 8

9 Pertussis ). :(acellular) - **,. (toxin..., - DTP-., 4, (DTaP: Diphtheria-Tetanus acellular Pertussis) , dtap 7 ( ) :, Bp. 180 Bp RSV Nelson et al [15]- 15,( direct fluorescent antibody " ) 29,. 14,,, RSV,. RSV.. 9

10 126 [16] Crowcroft et al, 9, 25, 6.,.RSV Saint Vincent de Paul-Cochin,- RSV-), 4 pertussis-pcr,.(pertussis.[17], Bordetella parapertussis Bp- Bp pertussis-pcr,.[18] 166 [19] Siberry et al : "- Walsh et al [18] RSV ) ( PCR", Bp.[18] pertussis-pcr 117 [20] Korppi and Hiltunen RSV 7,, '"-..[21], 6,- - '' 8.5% :, 10

11 Bp.(RSV,rhinovirus,influenza A ).[22] RSV [4] :... Bp,.. : Bp.1,,, : ().. Bp :.3. 11

12 12 : :. 475 ", ' '," : 4. : : ",,,. :.1. RSV.2. :,.". :. 3) ( ". 48. Bp DNA-PCR " IS481).(ptxA-Pr /."..1 :.,,,,,.

13 ,,,,, :..',,.2.,, :. : ,. :. Fisher's Exact 2 ) Mann-Whitney.(. Bp Positive 95% (p<0.10) P-value. (Chicago, Inc.) SPSS

14 :. 3.4, 475.(1) 38% 62% (73%) 346/474, RSV (6.1%) 29/474. (65%) 226/346 9/29,RSV (62%) 18/29. Bocavirus, Human Meta Pneumo Virus : (31%).(2) Bp (6.9%) 2/29,RSV Rhinovirus. Bp :. Bp.(3) 6 ) p<0.06,(14.6%) 2 (3.3%) 3.(4, 2-4, 2>) : Bp 2,(0,1,2, 3) ( 6<, 4-6, (OR: 36.84; 95% CI : ; p<0.006),,.(5),,,.,.,.(7 6) 14

15 15,,,/),.(,. ",. :1 N % N (. ) (,) (15.9) (96-0,6.2) 4< 184 (38.8) (15.2) (9.3) (12.4) (5.7) (24.00) 19 (4.0) (10.5) (4.0)

16 Bp+ (%) RSV+ (%) % (474) :2 N % 226 RSV+ ( ) % 18 Bp+ RSV % RSV % 73.0% 346 All RSV % 2 Bp+ ( ) % 9 + Bp+ 100% 6.1% 29 All Bp+ :3 2 p p 0.25 Bronchiolitis/Bp- (N=445) % N (. ) (16.1) N 445 Bronchiolitis/ Bp+ (N=29) % N (. (12.4) N 29 4<

17 :4 ( 3 )p Bp- Bp (5.1%) (7.9%) (14.6%) (3.3%) 3 17

18 18 :5, Bronchiolitis/Bp+ Bronchiolitis/Bpp VALUE N % N % ) ' 38 ( :6, Bronchiolitis/Bp+ Bronchiolitis/Bp- P VALUE N % N % N (. ) N P VALUE (12.3) 80-30, (12.1) 90-50, % (3.9) (4.5) , % (2.2) , (2.2), not normally distributed

19 19 :7, Bronchiolitis/Bp+ Bronchiolitis/Bp- P VALUE N % N % / N N P VALUE (3.3) 12-0, (2.4) 15-0, (1.2) 5-0, (1.1) ( /) (1.7) 6-0, (2.0) 14-0, ,0 (2.8) (2.4) 14-0, (3.1) 13, (4.2) 68, not normally distributed

20 20 :,, ,.[22] 50%-) (, 2-6.[1].. 2,,., Bp.Bp,., 2, ) (

21 21,. ". Bp..,.[23], 90%. [23]. 15% - 50%.[24].[24], 3.2% 15) (474. :.., :,,, " 4 8-9

22 22,,,,.[25] ", 2., Pediatrics.[23],,,.,Bp. ". Bp,. " [17] [22],() ()-".. : [17], Saint Vincent de Paul pertussis-RSV. 16% RSV.-RSV

23 highly "." predictive 6 205, [22]... 69%., PCR ". 6.(95%) (3.3%) 3. (14.6%) [22] Nuolivirta K et al ,1. 23

24 24, CDC [13],[12,14] 21 ).( ( ).() ".( ) :.1.,..2. LRT..3,,...4, clinical score system, "".

25 :.,.,

26 : :, (RSV) - Respiratory Syncytial virus,.,. (6.2%). : Bp.1,,, : ().. Bp :.3. :,, " 475, ',., , " ', :. 26

27 27 ",,. : 346 RSV (72.8%). 226 (65%). Bp 29 (6.1%), 18/29 (62%).RSV 9/29 (31%).RSV Bp (3.3%).p<0.06,(14.6%) 2,,.. :.,.,

28 ABSTRACT: Introduction: Acute bronchiolitis, a lower respiratory tract disease of infancy, is caused primarily by viruses. The peak incidence of severe bronchiolitis occurs in neonates, infants and toddlers in the winter months. While Respiratory syncytial virus (RSV) is responsible for most cases of bronchiolitis, coinfection with Bordetella pertussis is known to occur. For example, a recent study (Miron et al) found 6.2% of cases of infants <2 years admitted with bronchiolitis to hospitals in northern Israel to be co-infected. However, to date, little is known about the clinical presentation of this co-infection and more specifically, how Bordetella pertussis may affect the course of the disease. Goals: 1. To assess how Bp may affect the course of the disease: clinical presentation, severity and prognosis. 2. To identify risk factors associated with bronchiolitis-bp co-infection. 3. To review the utility of PCR testing of those infected with bronchiolitis. Subjects and Methods: 475 infants under the age of two years with an admission diagnosis of bronchiolitis were evaluated prospectively. The study was conducted between November 2005 and March 2006 at three hospitals in Northern Israel: Bnai Zion Medical Center, Rambam Medical Center in Haifa and Ha Emek Hospital in Afula. Demographic and epidemiological data were recorded and data were collected on patients' clinical presentation and hospital course. Subjects were categorized as either pertussis-positive bronchiolitis or pertussis-negative bronchiolitis.. 28

29 Results: RSV was found in 346 (72.8%) cases. Bp was identified in 29 (6.1%) cases, with 18 of these cases (i.e., 62% of all Bp cases) involving co-infection with RSV. In only 2 cases was Bp the sole pathogen detected. There were no epidemiological or demographic differences between the Bp+ and Bpbronchialitis patients. However, among infants <6 months, 2 doses of Bp vaccination were significantly more likely to be pertussis-positive than those with 3 doses of vaccination (14.6% versus 3.3%; p<0.06). There were no significant differences between the two groups with respect to the clinical course of the disease during hospitalization, treatment modality, the amount of time patients required supplemental oxygen, or rate of transfer to a Pediatric intensive care unit. Conclusions: Among children infected with bronchiolitis, no evidence was found to suggest that Bp is associated with the epidemiological characteristics, clinical course of the disease or its prognosis. These findings lead us to believe that there may be little benefit to the Bp-positive patient by identifying such patients as Bp positive. Nevertheless, there may be significant infection control ramifications associated with not identifying and treating such individuals. Additionally, the findings suggest the utility of multiple vaccinations against Bp, with infants <6 months of age who received 3 doses of vaccination having a significantly lower prevalence rate of pertussis relative to those who received 2 doses. While these findings suggest that 3 doses provide a higher level of protection than 1 or no doses, limited cell sizes made it impossible for us to do so. Accordingly, future research should replicate our analysis using a larger sample of Bp+ patients with greater variance in vaccination coverage. 29

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31 9. Mark A, Wendelboe, Van Rie A: Diagnosis of pertussis: a historical review and recent developments. Expert Rev. Mol. Diagn. 2006; 6; De Melker H, Versteegh F, Conyn-van Spaendocnk M, et al: Spesificity and sensitivity of high levels of immunoglobulin G antibodies against pertussis toxin in a single sample for diagnosis of infection with bordetella pertussis. J clin microbial 2000; 38; Rudolph CD, Rudolph AM, Hostetter MK, Lister GG, Siegel NJ. Rudolphs pediatrics 2003; 21th edition. New York: McGraw-Hill p Dodhia H, Crowcroft NS, Bramley JC, Miller E. UK guidelines for use of erythromycin chemoprophylaxis in persons exposed to pertussis.j Pub Health Med 2002; 24: Recommended antimicrobial agents for the treatment and postexposure prophylaxis of pertussis 2005.Atlanta,Ga: Centers for Disease Control and Prevention.Available at : on March 30, Dodhia H, Miller E. Review of the evidence for the use of erythromycin in the management of persons exposed to pertussis.epidemiol Infect 1998; 120:

32 15. Nelson WL, Hopkins RS, Roe MH, et al. Simultaneous infection with Bordetella pertussis and respiratory syncytial virus in hospitalized children. Pediatr Infect Dis. 1986;5: Crowcroft NS, Booy R, Harrison T, et al. Severe and 32nrecognized: pertussis in UK infants _erratum in Arch Dis Child. 2006;91:453_. Arch Dis Child. 2003;88: Cosnes-Lambe C, Raymond J, Chalumeau M, et al. Pertussis and respiratory syncytial virus infections. Eur J Pediatr. 2008;167: Walsh PF, Kimmel, L, Feola M, et al. Prevalence of Bordetella pertussis and Bordetella parapertussis in infants presenting to the emergency department with bronchiolitis. J Emerg Med Mar;40(3): Epub 2008 Dec Siberry GK, Paquette NR, Ross TL, et al. Low prevalence of pertussis among children admitted with respiratory symptoms during respiratory syncytial virus season. Infect Control Hosp Epidemiol. 2006;27: Korppi M, Hiltunen J. Pertussis is common in nonvaccinated infants hospitalized for respiratory syncytial virus infection. Pediatr Infect Dis J.2007;26: Greenberg D, Bamberger E, Ben-Shimol S, et al. Pertussis is under diagnosed in infants hospitalized with lower respiratory tract infection in the pediatric intensive care unit. Med Sci Monit. 2007;13:CR475 CR Nuolivirta K, Koponen P, He Q, Halkosalo A, Korppi M, Vesikari T, Helminen M. Bordetella pertussis infection is common in nonvaccinated infants admitted for bronchiolitis. Pediatr Infect Dis J,2010;29(11):

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