Streptococcus Pneumonia Serotypes in Newly Developed State of Qatar

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State of Qatar: Consideration for Conjugate Vaccine. *AI Khal A.L. ... Department of Medical Statistics & Epidemiology, Hamad Medical Corporation, Doha, Qatar.
QATAR MEDICAL JOURNAL | VOL. 16 / NO. 2 / NOVEMBER 2007

ORIGINAL

STUDY

Streptococcus Pneumonia Serotypes in Newly Developed State of Qatar: Consideration for Conjugate Vaccine *AI Khal A.L.,**E1 Shafie S.S.,**A1 Kuwari J.,***Bener A. * Infectious Diseases, Department of Medicine ,** Laboratory Medicine & Pathology Department *** Department of Medical Statistics & Epidemiology, Hamad Medical Corporation, Doha, Qatar

Abstract:

Introduction:

Objectives: The objective of the study was to determine prevalent pneumococcal serotypes causing infections in different age groups, their susceptibility to fi-lactams and macrolides and whether these serotypes are covered by the conjugated pneumococcal vaccines. Methods: Streptococcus pneumonia strains isolated from different patients at Hamad Medical Corporation, Microbiology Laboratory between September 1999 and July 2000 were sent to Statum Serum Institute in Denmark for serotyping. The strains were tested for their susceptibility to penicillin, ceftriaxone and erythromycin by Vitek 2 machine (bioMerieux, France) at Hamad Medical Corporation, Microbiology Laboratory.

S.pneumoniae is an encapsulated Gram-positive bacterium. The capsule consists of polysaccharides, which form the basis of serogroups and serotypes. More than 90 serotypes within 45 serogroups are present with no immunologic cross reactivity between serogroups, but some cross reactivity within some serogroups and some protection(1). Infants usually become colonized at about 3 to 4 months of age and remain colonized for about 4 months with given serotypes(2,3).

Results: Predominant serotypes in children < 2 years were: 6A, 6B, 9V, 11A, 14,19A, 19F and 23 F, predominant serotypes in children between 2-7years were: 3, 6B, 15B, 19A, 19F and 23F, while predominant serotypes in adults were: 3, 8, 9V, 14,15B, 20 and 22F. In children less than 2 years, the 7-valent and 9-valent conjugate vaccines covered 52% of serotypes. 33% of strains were moderately resistant to penicillin, 27% showed high-level resistance to penicillin, 30% resistant to erythromycin and 2% resistant to ceftrixone. Conclusion: The 7-valent and 9-valent vaccines offer similar coverage of serotypes in children less than 2 years while the 11-valent vaccines offers 55% coverage. This difference is not statistically significant. Resistance to penicillin was high which leaves ceftriaxone as the drug of choice for empirical treatment of invasive pneumococcal diseases. Key words:

Address for

S.pneumoniae, resistance

conjugate vaccine,

antibiotic

The diversity of pneumococci and the development of antibiotic resistance necessitate the availability of S.pneumoniae vaccine. The first capsular type vaccines, (the 14 and 23-valent) are composed of the sefogroups most commonly associated with the human infections(9). However, these vaccines are unable to elicit adequate antibody response in children younger than 2 years, the most vulnerable age group for invasive disease(10,15). To overcome this problem, 3 protein conjugated vaccines were introduced i.e. the 7-valent (including serotypes (4,6B, 9V, 14,18C, 19F, 23F), the 9-valent (7 valent vaccine with serotypes 1 & 5) and 11-valent (9-valent vaccine with serotypes 3 and 7F) vaccines.

Methods:

correspondence:

E-mail: [email protected]

There is strong association between resistance pattern and serotypes. Currently most clinical isolates with high-level resistance to fi-lactam antibiotics belong to serogroups 6,9,14,19, and 23(6,7,8). For reasons not well understood, many of these serogroups have also acquired resistance to other drugs.

We studied the prevalent serotypes in Qatar in different age groups, their resistance to B-lactam antibiotics and erythromycin and whether the new conjugate vaccines cover these prevalent serotypes.

Abdul LatifAl Khal, MD, FACP Department of Medicine, Hamad Medical P. O. Box 3050, Doha, Stateof Qatar

The pneumococcus is responsible for a broad spectrum of diseases. It is a major cause of community acquired bacterial pneumonia, causes the majority of otitis media in children, and a leading cause of bacterial meningitis and septicaemia(4'5).

Corporation

From September 1999 to July 2000-148 strains of S.pneumoniae were isolated from different specimens obtained from patients with different age groups.

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Streptococcus

Pneumoniae

Serotypes and Conjugate

Al Khal A.L., et.al.

Vaccine

Strains were identified by conventional methods including gram stain, susceptibility to optochin, bile solubility and latex agglutination. The antimicrobial susceptibility testing was performed by the Vitek 2 (bioMerieux, France). Interpretation of the results was according to National Committee of Clinical Laboratories Standards (NCCLS). The serogrouping was performed at the Statum Serum Institute, Copenhagen.

22 different serotypes were isolated from children < 2 years. As shown in Table 4, predominant serotypes were 19F, 6A, 19A, 6B, 23F, 9V, 11A and 14. While in children > 2 years of age 15 serotypes were isolated with serotypes 19F, 23F, 3, 6B, 15B and 19A as the predominant serotypes (Table 5). In adults 19 serotypes were identified (Table 6). Table 4: Serotypes in children below 2 years

Results: 148 strains were sent for typing, 15 strains were rough and only 133 strains were typable. Of these 66 strains isolated from children < 2 years, 36 from children > 2 (2-71/2 years) years, and 31 from adults (40-82 years). Sites of infections for the different age groups was shown in Table 1, 2, 3. Table 1: Sites of infections in children below 2 years Infections

n(%)

Children < = 2 Years Eye Infections

36 (55%)

Ear Infections

19 (29%)

Respiratory Tract Infections

8 (12%)

Blood Stream Infections

3 ( 5%)

Cerebrospinal Fluid Infections

0 ( 0%)

Total

66

Table 2: Sites of infections in children below 2 years

Serotypes Children < 2 Years 19F

17 (26%)

6A

7(11%)

19A

6 ( 9%)

6B

6 ( 9%)

23F

4 ( 6%)

9V

3 ( 5%)

11A

3 ( 5%)

14

3 ( 5%)

Other serotypes were: 7F, 10A, 15A, 15C, 16F, 18B, 18C, 23A, 23B, 24F, 29, 33A, 35B, 35F

Table 5: Serotypes in children > 2 years Serotypes

n(%)

Children > 2 Years 19F

5 (14%)

23F

5 (14%)

3

4(11%)

27 (75%)

6B

4(11%)

Respiratory Tract Infections

5 (14%)

15B

4 ( 6%)

Eye infection

2 ( 6%)

19A

3 ( 8%)

Cerebrospinal Fluid Infections

1 ( 3%)

Miscellaneous Infections

1 ( 3%)

Blood Stream Infections

0 ( 0%)

Infections

n(%)

Children > = 2 Years Ear Infections

Total

36

Table 3: Sites of infections in adults aged 40-80 years Infections Respiratory Tract Infections

n(%) 19(61%)

Ear Infections

7 (23%)

Blood Stream Infections

4 (13%)

Eye Infections

1 ( 3%)

Total

26

n(%)

31

Other serotypes were: 5, 6A, 13,14, 22A, 23B, 28A, 34, 35B

Table 6: Serotypes in adults aged between 40-80years Serotypes

n(%)

9V

4 (13%)

3

3 (10%)

14

3 (10%)

8

3 (10%)

20

2 ( 6%)

22F

2 ( 6%)

15B

2 ( 6%)

Other serotypes were: 12F, 15A, 15C, 16F, 17F, 19A, 19F, 23A, 23F, 35C, 40,48

QATAR MEDICAL JOURNAL | VOL. 16 / NO. 2 / NOVEMBER 2007

Streptococcus

Pneumoniae

Serotypes and Conjugate

Potential serogroups coverage by the 3 types of conjugate vaccines was shown in Figure 1. There were nine invasive infections in all age groups, 7 cases of septicaemia and one case of meningitis. Serotypes causing these infections were: 6B, 7F, 16F, 19A, 22F, 23F, 40 and 48. Only three were included in the conjugated vaccines. Figure 1: Potential Serogroup Coverage by conjugate vaccine formulations.

Young Children < 2 Years

Young Children > 2 Years

Al Khal A.L., et.al.

Vaccine

Adults

44 (33%) of strains showed intermediate level resistance to penicillin and 36 strains (27%) were highly resistant to penicillin. The main serogroups with reduced penicillin susceptibility were 6,14,19 and 23. Main serogroups with highlevel resistance to penicillin were 23 and 19. Only 2 strains were found to be resistant to ceftriaxone both belonging to serotype 23F. Erythromycin resistance was recorded as 30%.

Discussion: S.pneumoniae remains an important cause of respiratory tract infections in adults worldwide and in Qatar (Tables) and important cause of eye and ear infections in children (Table 1, 2). The complications of these infections caused by S.pneumoniae are usually very severe e.g. meningitis and bacteraemia(12,13). Penicillin resistant pneumococci have emerged throughout the world in recent years. In USA a 60-fold increase from 1987 to 1999 was reported(14). European data shows major variation between countries from 4% in Belgium(15) to 44% in Spain(16). In our study 33% of serotypes were moderately resistant to penicillin and 27% show high level resistance, while resistance

to erythromycin - 2nd drug of choice - was as high as 30%. All strains remain sensitive to ceftriaxone except 2 belonging to serotype 23F (2%). This high level resistance to penicillin necessitate the introduction of an effective vaccine which cover the prevalent serotypes, in the at risk groups i.e. infants, the elderly and the immunocompromised. Most prevalent serogroups shown in Table 4, 5 & 6 were included in the polysaccharide vaccine, which will not protect children < 2 years due to their poor response to polysaccharide antigens. Conjugate vaccines were developed by coupling capsular polysaccharide to a protein carrier. This process endows the conjugated polysaccharide with certain properties of a T-cell dependant antigen, allowing it to be antigenic in infants(17'18). These vaccines include the 7-valent, the 9-valent and the 11-valent vaccines. Assuming similar efficacy, the coverage confirmed by the 7-valent vaccines varies from country to another because of the geographic and epidemiologic differences in serotype distribution and disease pattern. For example, 7-valent vaccine serogroups cause 70-80% of invasive disease in young children in USA, Canada, Europe and Africa, but only 65% of disease in Latin America and Asia. Serogroups in the 9-valent formulation cause 80-90% of pneumococcal disease in most regions of the world except Asia (66%)(11'9). In our study as shown in Fig.l, in children < 2 years, the 7-valent and 9-valent vaccines offer similar coverage (52%) while the 11-valent vaccine offer 55% coverage, a difference which is not statistically significant. However, most of the infections were eye and ear infections with only 3 cases of invasive disease. Ideally a vaccine that could protect against pneumococcal pneumonia and otitis media would also protect against meningitis and septicaemia in young children™. Further studies to define the prevalent serotypes causing invasive disease in this age group will be essential to decide the exact coverage offered by the conjugated vaccines. We conclude that the prevalent serotypes causing noninvasive infections in infants < 2 years in Qatar were 6A, 6B, 11 A, 14, 19A, 19F and 23F with only 53% coverage by 7valent and 9-valent vaccines. Penicillin resistance is high (60%); this leaves ceftriaxone as the drug of choice for empirical therapy of pneumococcal infections, which mandate further studies to define the common invasive serotypes and their coverage by conjugated vaccines.

References: 1. Henrichsen J. Six newly recognized types of Streptococcus pneumonia. J. Clin Microbio 1995; 33: 2759-2760. 2. Gray BM, Dillon HC JR. Epidemiologic studies of Streptococcus pneumonia in infants antibody to type 3, 16, 14 and 23 in the first two years of Infect Dis. 1988; 158: 948-953.

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Pneumoniae

Serotypes and Conjugate Vaccine

Immunogenicity and tolerance of a 7-Valent Pneumococcal Conjugate vaccine in Nonresponders to the 23-Valent Pneumococcal Vaccine, Infection and Immunity, 2000,68 (3): 1435.1440,. 5. Wenger JD, Hightower AW, Facklam RR, Gaventa S, Broome CV. Bacterial meningitis in the United States, 1986, Report of a multistate surveillance study, J. Infect Dis 1990; 162: 1316-1323. 6. Klugman KP. Pneumococcal resistance to antibiotics. Clin Microbio Rev. 1990; 3: 171-196. 7. Gherardi GC, Whitney R, Racklam and Beal. Major related sets of antibiotic resistant penumonococci in the United States as determined by pulsed-field gel electrophoresis and pbplapbp2b-pbp2x-dhf restriction profiles. J. Infect Dis. 2000; 181:216-219. 8. Stephanie J. Schrag, Bernard B and Scott F. Dowell. Limiting the spread of resistant pneumococci biological and epidemiological evidence for the effectiveness of alternative interventions. Clin Microbio Rev. 2000; 13: 588-601. 9. Moroney, J A. Farley, L. Harrison, J. Patterson, M. Cetron and A. Schuchat 1997. Therapy and outcome of meningitis caused by drug-resistant Streptococcus pneumoniae in three US cities 1994-1996, abst. 48. In abstract of the 35th annual meeting of the Infectious Diseases Society of America. 10. Sheldon L, Kaplan and Edward O. Mason JR. Management of Infections due to antibiotic resistant Streptococcus pneumonia. Clin Microbiol Rev 1998; 11(4): 628-644. 11. Obaro SK. The new pneumococcal vaccines. Clin Microbiol Infect 2002; 8(10): 623-644. 12. Fridman E, Gill IC, Heal G. Central nervous system complication associated with acute otitis media in childrenlaryngoscope 1990; 100: 149-151.

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13. Konppari G, et al. Pneumococcal acute otitis media in children. Clin Microbiol Infect 2000; 6: 69-73. 14. Beiman RF, et al. Emerging of drug resistant pneumonococcal infection in the United States. J. Am Med Assoc 1994; 271: 1831-1835 15. Verhaegen J, Glupczynski Y, Verbist L, et al. Capsular types and antibiotic susceptibility of pneumococcus isolated from patients in Belgium with serious infections 1980-1993. Clin Infect Dis 1995; 20: 1339-1345. 16. Fenoll A, Martin Bourgon C, Munoz R, Vicioso D, Casaql J. Serotypes distribution and antimicrobial resistance of S.pneumonia isolated causing systemic infections in Spain, 1979-1989. Rev Infec Dis 1991; 13: 56-60. 17. Insel RA and Anderson PW. Oligo saccharide protein conjugate vaccines induce and prime for oligoclonal log, G antibody responses to the Haemophilus influenzae b capsular polysaccharide in human infants. J. Exp Med 1986; 163:262-269. 18. Steubgijf MGK, Edwards H, Keyserling ML, Thomas C, Jhonson D, Madore M, and Hogerman DH. Arandomized comparison of three bivalent Streptococcus pneumonia glycoprotein conjugate vaccines in young children, effect of polysaccharide size and linkage characteristics. Pediatric Infect Dis J. 1994; 13: 368-372. 19. HansdroffWP, Bryant J, Paradiso PR, Siber GR. Which pneumococcal serogroups cause the most invasive disease implications for conjugate vaccine formulation and use, Part 1. Clin Infect Dis 2000; 30: 100-121. 20. David E. Brile, et al. Pneumococcal diversity consideration for new vaccine strategies with emphasis on pneumococcal surface protein A. Clin Microbiol Rev 1998; 11(4): 645-657.

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