Pneumococcal Vaccine in Children: current situation

Transcription

1 Pneumococcal Vaccine in Children: current situation LAU Yu Lung Chair Professor of Paediatrics Doris Zimmern Professor in Community Child Health LKS Faculty of Medicine, The University of Hong Kong Chairman Working Group on Pneumococcal Vaccination Centre for Health Protection

2 Outline Pneumococcal disease Pneumococcal vaccination Surveillance of Invasive Pneumococcal Diseases (IPD) Overall disease burden Case-based surveillance of paediatric IPD

3 Spectrum of pneumococcal infections PL Ho 27

4 Day 7 Day Day USG Left chest Day 2 Day 6 Day 2 USG Right pleura Day 26 Day 55 CAP in a child: K Leung & YL Lau 25, QMH

5 Outline Pneumococcal disease Pneumococcal vaccination Surveillance of Invasive Pneumococcal Diseases (IPD) Overall disease burden Case-based surveillance of paediatric IPD

6 Pneumococcal Vaccination for Infants in Hong Kong () The Scientific Committee on Vaccine Preventable Diseases (SCVDP) under the CHP of DH review and develop strategies for public health management of vaccinepreventable infections and their risk factors in the light of changing epidemiology and advances in medical science. SCVPD considers the following factors when deciding whether to introduce new vaccines in the Hong Kong Childhood Immunisation Programme (HKCIP) - Epidemiology (incidence and mortality rates) Efficacy & safety Availability of other preventive measures Economic analysis Public acceptance Administrative arrangements (delivery mechanism)

7 Economic analysis of Pneumococcal Conjugate Vaccine (PCV7) Benefit-cost ratio favourable Net cost per life-year saved is estimated to be HK$55, (25% per capita GDP in HK) Recommended to incorporate of PCV7 in the Hong Kong Childhood Immunisation Programme 2, 4, 6 months, then at year old [2, 4 months, then at year old is also adequate] SCVPD, CHP Oct 28

8 Conjugate pneumococcal vaccine Serotypes included in the three licensed pneumococcal conjugate vaccines Serogroup/ serotype Formulation 4 5 6A 6B 7F 9V 4 8C 9A 9F 2F PCV-7 PCV- PCV- PCV, pneumococcal conjugate vaccine., serotype included in the vaccine;, cross-protection expected from serotype 6B. Current Opinion in Infectious Diseases 2; 2:27

9 Pneumococcal vaccination in the Hong Kong Childhood Immunisation Programme (HKCIP) A standard -dose primary series of Pneumococcal Conjugate Vaccine (PCV) at 2nd, 4th and 6th months of age with a booster at 2-5 months Vaccine Available in market since Included in HKCIP since Birth cohort covered with at least dose PCV7 Jul 25 Sep 29 Sep 27* PCV Aug 29 Oct 2 Oct 29 PCV Jul 2 Dec 2 Dec 2 *One-off catch-up programme for eligible children born between Sep 27 to June 29.

10 PCV vaccination coverage in Hong Kong DH conducted territory-wide immunisation coverage surveys on children aged 2 to 5 in Hong Kong every years. Survey in 29 indicated 2% of local-born children of birth cohorts 2 to 26 ever received pneumococcal vaccines []. Survey in 22 covered children born in 26 to 29 [2]. Among those eligible for PCV standard regimen (i.e. those born on or after July 29), high vaccination coverage was achieved: PCV Coverage (%) (n=469) st dose nd dose 99. rd dose 97.4 Booster 94.7 Source: [] Immunisation coverage survey 29, Centre for Health Protection, Department of Health [2] Immunisation coverage survey 22, Centre for Health Protection, Department of Health

11 Outline Pneumococcal disease Pneumococcal vaccination Surveillance of Invasive Pneumococcal Diseases (IPD) Overall disease burden Case-based surveillance of paediatric IPD

12 Surveillance of IPD in HK Laboratory surveillance by PHLC, DH Before introduction of PCV into HKCIP, there has been ongoing laboratory surveillance to capture IPD disease burden Serotyping of positive culture isolate of pneumococci The number of isolates in between 27 and 29 only include blood, CSF, pleural fluid and pericardial fluid specimens Extended to include all specimens from normally sterile sites since 2 Participating hospitals Nine out of the microbiology laboratories of public hospitals in 27 All laboratories of public hospitals sent the isolates to PHLC from 28 onwards Private laboratories joined the surveillance system since 28 Voluntary reporting of Paediatric IPD To enhance collection of clinical and epidemiological information, reporting of paediatric IPD cases by physicians started in 24. IPD becomes notifiable Starting from 9 Jan 25, IPD becomes notifiable. All doctors are required to report IPD cases of any age to the Department of Health.

13 Incidence of IPD in Hong Kong PCV7 PCV PCV 27-24: PHLSB lab surveillance (bacterial culture only) 25 onwards: IPD notification to CHP (bacterial culture + PCR)

14 Age-specific incidence of IPD in Hong Kong, 27 to Apr : PHLSB lab surveillance (bacterial culture only) 25 onwards: IPD notification to CHP (bacterial culture + PCR)

15 Seasonal pattern IPD is more common in winter and spring, with peaks from December to February 27-24: PHLSB lab surveillance (bacterial culture only) 25 onwards: IPD notification to CHP (bacterial culture + PCR)

16 Serotype replacement Serotypes covered by PCV but not by PCV7 (i.e. serotypes, 5, 7F in PCV and PCV and serotypes, 6A and 9A in PCV) become predominant in recent years Serotype replacement is more profound among the younger age groups Serotype distribution is relatively stable among the adults

17 Serotype replacement (aged under 8) Note: small numbers especially for years 24 and 25

18 Serotype replacement (aged 8 and above)

19 Outline Pneumococcal disease Pneumococcal vaccination Surveillance of Invasive Pneumococcal Diseases (IPD) Overall disease burden Case-based surveillance of paediatric IPD

20 Case-based surveillance of Paediatric IPD In 24, voluntary reporting of Paediatric IPD was initiated to enhance collection of clinical and epidemiological information, reporting of paediatric IPD cases by physicians started in 24. To further enhance case-based surveillance, IPD was made notifiable starting 9 January 25. All doctors are required to report IPD cases of any age to the Department of Health.

21 A total of 7 cases were reported from 2 Jan to Dec 24 through the voluntary reporting system. Since IPD becomes notifiable in 25, 9 cases were reported from 9 Jan to Apr, compared to 2 cases in the first four months of 24.

22 Paediatric IPD cases 7 and 9 cases were reported in 24 and 25 (up to Apr) respectively Year 24 Jan-Apr 25 Demographic characteristics # (%) # (%) Age group Gender Male Female Ethnicity Chinese Indian Usual place of residence HK Mainland China Data as at May 2

23 Paediatric IPD cases Year 24 Jan to Apr 25 Characteristics # (%) # (%) Underlying medical conditions Concurrent infection (with known laboratory confirmation) No Yes No Yes Prematurity Speech delay ADHD History of Reyes syndrome Eczema History of use of ketamine Enterovirus/ Rhinovirus RSV Influenza A (H) Influenza A (H) Rhinovirus Parainfluenza Coronavirus OC4 Mycoplasma pneumoniae RSV & Influenza A(H) RSV & Rhinovirus Enterovirus/ Rhinovirus & Human metapneumonic virus Parainfluenza type 4 & Human Metapneumonic virus *This patient also has history of recurrent bronchiolitis *

24 (A) Detection of Gram-positive cocci (arrows) with use of Lillie- Twort Gram stain of lung tissue (B) Immunohistochemical staining of multiple S. pneumoniae (arrows) with use of immunoalkaline phosphatase with naphthol-fast red and hematoxylin counterstain

25 Timing of peak influenza correlated with the timing of excess pneumococcal pneumonia in fall of 29 among 5 64-year-olds in USA. (Suggesting the association of secondary pneumococcal infection with influenza diseases) Weinberger D M et al. J Infect Dis. 22;25:

26 (a) (b) (c) (d) (e) (f) Paediatric IPD cases 7 and 9 cases were reported in 24 and 25 (up to Apr)respectively 2 cases of bacteremic pneumonia also had pleural effusion; one case of bacteremic pneumonia also had pleural empyema and otitis media case of pneumonia with pleural empyema also presented with otitis media case with lung abscess also presented with cerebral oedema, subarachnoid haemorrhage, intraventricular haemorrhage, ARDS case with HUS also had DIC case of pneumonia with pleural effusion also has febrile convulsion case of pneumonia with pleural empyema also has septic shock Preliminary data as at May 25 Year 24 Jan to Apr 25 Characteristics # (%) # (%) Clinical manifestation Other manifestations Bacteremic pneumonia Pneumonia with pleural/ parapneumonic effusion Pneumonia with pleural empyema Meningitis Bacteremia with URTI symptoms Lung Lung abscess HUS/ renal failure respiratory distress 8 (a) 6 (b) (c ) (d) (e) 5 (f) 22 56

27 24 children with pneumococcal pneumonia with necrotising pneumonia Serotype infection was associated with necrosis (OR 4.67) Clinical Infectious Diseases 28; 46:46-52

28 Late Complications of Necrotizing Pneumonia Pediatr Pulmonol 2 doi:.2/ppul.2294

29 ^ Duration of ICU admission is pending for one case ; *excluding case pending discharge outcome Paediatric IPD cases 7 and 9 cases were reported in 24 and 25 (up to Apr) respectively Year 24 Jan to Apr 25 Other treatments received # (%) # (%) Treatment Mechanical ventilation Renal replacement therapy (haemodialysis) Surgical intervention Chest drain Decortication Hospitalization # (%) # (%) Reporting hospital Duration of hospital stay ICU admission admission Outcome Public hospitals Private hospitals DH Range Median No Yes Recovered Death Still hospitalized ICU stay (duration) ICU stay (median) ^ 7^ * 8* 6 Pending Pending

30 Paediatric IPD cases fatal cases out of 7 cases in 24 The first fatal case was a 5 year old boy who had bacteremic pneumonia with pleural effusion. His NPA tested positive for influenza A (H) by RT-PCR and RSV antigen. Serotype pneumococci was isolated from his blood culture. He received doses of PCV7 but no seasonal influenza vaccine. The second fatal case was a year old girl from Guangdong, Mainland China. She had bacteremic pneumonia with respiratory distress and septic shock. Serotype 9A pneumococci was isolated from her blood culture. She did not receive any PCV. The third fatal case was a 2 year old girl who had pneumonia with pleural effusion. Her pleural fluid collected on 28 Oct tested positive for serotype pneumococci by PCR. NPA taken on 22/ was positive for RSV and rhinovirus. Her situation was complicated by transfusion related acute lung injury, aspiration and right heart failure. Blood culture collected on Dec grew multidrug resistant Stenotrophomonas maltophilia. Patient died on 5 Dec 24

31 Co-infection of influenza virus and Streptococcus pneumoniae increases mortality and reduces virus-specific antibodies Co-infection increases mortality Co-infection reduces B cells in spleen Co-infection reduces IgG secreting cells Co-infection reduces virus-specific IgG, IgM and IgA in the lu J Virol. 25; 89:4:2-2

32 Paediatric IPD cases, Jan 24-Apr 25 Serotype distribution of Paediatric cases, 2 Jan 24 to Apr 25 5 covered by PCV but not by PCV covered by PCV7 Not covered by PCV7/ PCV 9V 4 2F 9A 8 5A 5C 2A B/F Serotypes is predominant (6%), followed by serotype 9A (2%) All 9 cases notified in 25 were caused by serotype. Data as at May 25 - year 2-4 years 5-7 years

33 Covered by PCV? Yes No Serotype Paediatric IPD cases Age group (Years) PCV dose Total (Sub-total) V A A (Sub-total) F A 5-7 5C 2-4 2A 2-4 B/F 2-4 Total For the 29 cases caused by serotype pneumococci, (4%) had received or 4 doses of PCV whereas 4 (48%) did not receive any. For the 9 cases caused by serotype 9A pneumococci, (%) had received 4 doses of PCV, 2 (22%) received dose whereas the remaining 6 (67%) did not receive any.

34 PCV Vaccine Effectiveness in UK Post-licensure PCV VE evaluated using Indirect cohort method in UK IPD cases collected under national surveillance was used (.5 years and about 7 cases) PCV shown to provide significant protection for most of the vaccine serotypes VE for serotype was not significant Source: Andrews N et al. Lancet. Vol 4 Sep 24

35 Conclusion High vaccination coverage is achieved after introduction of PCV in routine immunisation. There is significant reduction in IPD incidence among children aged under two after introduction of PCV vaccination in the HKCIP. PHLSB laboratory surveillance system indicated changes in the predominant serotypes causing IPD in Hong Kong, with serotype being the main cause of IPD in recent years. In addition to laboratory surveillance, notification of IPD cases by frontline physicians provided an opportunity to collect detail pertinent information in a timely manner. IPD cases reported to surveillance system can be used to evaluate vaccine effectiveness of PCV. More data is needed in view of the relatively low incidence in Hong Kong.

36 Acknowledgement Members of SCVPD Members of the Working Group on Pneumococcal Vaccination Doctors reporting cases and providing clinical information All laboratories participating the laboratory surveillance of IPD

37 Thank you