Serotype Changes in Adult Invasive Pneumococcal Disease in the Vaccine Era with Special Reference to Serotype 6E

Takamatsu A¹*, Noguchi M², Ito M³, Matsuzaka S¹, Kawaguchiya M⁴, Kobayashi N⁴ and Seriwaza Y¹

¹Department of Medicine and Infectious Diseases, Teine Keijinkai Hospital, Japan

²Department of Genetic Medicine, Hokkaido University, Japan

³Department of Microbiology, Teine Keijinkai Hospital, Japan

⁴Department of Hygiene, Sapporo Medical University, Japan

*Corresponding author: Takamatsu A, Department of Medicine and Infectious Diseases, Teine Keijinkai Hospital, Japan

Received: August 19, 2016; Accepted: September 28, 2016; Published: October 03, 2016

Abstract

Background: Despite the decreased incidence of pediatric Invasive Pneumococcal Disease (IPD) due to Streptococcus pneumoniae vaccine serotypes with the advent of pneumococcal vaccines, pediatric IPD cases due to non-vaccine serotypes have increased. However, it remains unclear whether similar trends exist among unvaccinated adult populations. In this observational study, we investigated the clinical and microbiological characteristics of adult patients with IPD.

Methods: Medical records of adult patients with documented IPD at Teine Keijinkai Hospital in Sapporo, Japan, were reviewed between January 2015 and December 2015. Serotypes and genotypes were verified by multiplex PCR and Multi-Locus Sequence Typing (MLST).

Results: Four of seven patients with IPD had a past history of malignancy. None of the patients previously received pneumococcal vaccination. The most common IPD manifestation was pneumonia (four patients). All patients received susceptible antibiotics as an initial therapy. Multiplex PCR and MLST showed non-vaccine serotypes in six cases; one of which was serotype 6E. Two patients infected with non-vaccine serotypes died during their hospital stay.

Conclusion: These findings suggested that changes in serotypes responsible for IPD in adults were potentially affected by pneumococcal vaccination and that improving pneumococcal vaccine coverage in both pediatric and adult populations might provide clinical benefit.

Keywords: Streptococcus pneumoniae; Invasive pneumococcal disease; Vaccine

Abbreviations

IPD: Invasive Pneumococcal Disease; MLST: Multi-Locus Sequence Typing; PCV7: 7-Valent Pneumococcal Conjugate Vaccine; PCV13: 13-Valent Pneumococcal Conjugate Vaccine; PCVs: Pneumococcal Conjugate Vaccines; PBP: Penicillin-Binding Protein; PPSV23: 23-Valent Pneumococcal Polysaccharide Vaccine

Introduction

Vaccination strategy for pneumococcal disease is the cornerstone for preventing life-threatening Invasive Pneumococcal Disease (IPD). In Japan, similar to that observed in most countries, 7-Valent Pneumococcal Conjugate Vaccine (PCV7) was incorporated into the national routine immunization program for children in April 2013 and was later replaced by 13-Valent Pneumococcal Conjugate Vaccine (PCV13) in November 2013. PCV13 coverage rate among children is over 90% [1], which is higher than that in other countries and responsible for the drastic decrease in the incidence of IPD due to vaccine serotypes in children. However, the incidence of IPD due to non-vaccine serotypes has increased [1,2]. Although some studies suggested that a decrease in the incidence of IPD due to vaccine serotypes in adults was an indirect effect of Pneumococcal Conjugate Vaccines (PCVs), the existence of such a trend remains unclear [2,3]. Thus, we conducted an observational study on adult IPD cases at a single tertiary center in Japan to elucidate the clinical and microbiological characteristics of patients.

Materials and Methods

Medical records of adult patients >18 years with documented IPD at Teine Keijinkai Hospital, Japan, were retrospectively reviewed (January 2015-December 2015). Vitek^® 2 System (bioMerieux, France) was used for bacterial identification and antibiotic susceptibility testing of all Streptococcus pneumoniae isolates following the Clinical and Laboratory Standards Institute guidelines [4]. S. pneumoniae serotypes, macrolide resistance gene profile and Penicillin-Binding Protein (PBP) genotypes were determined by multiplex PCR; sequence analysis was employed for Multi-Locus Sequence Typing (MLST) [5].

Results

Seven patients (three males) with a mean age of 54 (range, 33- 84) years were diagnosed with IPD during the study period (Table 1). Four patients had a history of malignancy. None were previously vaccinated with PCV13 or 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23). Four patients had clinical manifestations of pneumonia. All patients received susceptible antibiotics as an initial therapy. Except for one S. pneumoniae isolate, the remaining six isolates belonged to the non-PCV13 serotypes. One isolate was serotype 6E. All seven isolates carried macrolide resistance genes; six isolates exhibited PBP mutations. Two patients with IPD due to non-vaccine S. pneumoniae serotypes died during the course of hospitalization.

Table 1: Clinical and microbiological characteristics of invasive pneumococcal disease among the study cohort.




  
    Case 
    Age 
    Sex 
    Diagnosis 
    Comorbidities 
    Vaccine Status 
    Treatment 
    Outcome 
    Serotype 
    pbp genotype* 
    Macrolide resistant gene 
    ST 
    PCG MIC (�g/mL) 
  
  
    1
    61
    Male
    Lung
    Malignancy
    None
    CFPM
    Died
    6C
    gPISP (pbp2x)
    ermB
    2924
    0.06
  
  
    Abscess
    →VCM
  
  
    2
    79
    Male
    Pneumonia
    DM
    None
    ABPC
    Cured
    6E
    gPRSP
    ermB
    90
    0.12
  
  
    3
    84
    Female
    Pneumonia
    Cirrhosis
    None
    CTRX
    Cured
    23F
    gPRSP
    mefA/E
    10409
    1
  
  
    →ABPC
  
  
    4
    38
    Female
    Peritonitis
    Malignancy
    None
    CFPM
    Died
    23A
    gPSSP
    ermB
    2572
    0.25
  
  
    →CTRX→CLDM
  
  
    5
    33
    Female
    Iliopsoas Abscess
    None
    None
    CTRX
    Cured
    15B
    gPISP (pbp2x)
    ermB
    199
    0.12
  
  
    →LVFX
  
  
    6
    54
    Female
    Pneumonia
    Malignancy
    None
    CTRX
    Cured
    38
    gPISP (pbp2x)
    mefA/E
    6429
    0.06
  
  
    7
    60
    Male
    Tumor Infection
    Malignancy
    None
    CFPM
    Cured
    15A
    gPRSP
    ermB
    63
    2
  
  
    →LVFX
  
  
    CFPM
  
  
    →LVFX
  
  
    PCG: Penicillin G; ST: Sequence Type; MIC: Minimal    Inhibitory Concentration; DM: Diabetes Mellitus; CFPM: Cefepime; VCM: Vancomycin;    ABPC: Ampicillin; CTRX: Ceftriaxone; CLDM: Clindamycin; LVFX: Levofloxacin,    PSSP: Penicillin-Susceptible Streptococcus Pneumoniae; PISP:    Penicillin-Intermediate S. Pneumoniae; PRSP: Penicillin-Resistant S.    Pneumoniae
      *Penicillin-Binding Protein (PBP) gene genotype was    presented as gPSSP (presence of three normal pbp genes: pbp1a, pbp2x, and    pbp2b), gPISP (presence of one or two altered pbp genes) and gPRSP (three    altered pbp genes).



Table 1: Clinical and microbiological characteristics of invasive pneumococcal disease among the study cohort.

Discussion

Here IPD occurred in unvaccinated patients, including those with malignancies. The incidence of IPD due to PCV13 serotypes was 54% [1]. Here non-PCV13 serotypes caused IPD in six cases. These results were consistent with a study by Lexau, et al. who reported that PCVs had an indirect effect on the adult population [6]; PPSV23 vaccination of elderly people >65 years and immunocompromised individuals should be encouraged to facilitate coverage for non-PCV13 serotypes. IPD due to serotypes 22F, 6C, 23A and 15C are increasing since PCV introduction [1]. Here two cases with serotype 6C and 23A had poor outcomes; further supporting concerns of increased mortality risk in patients with IPD due to virulent non-vaccine serotypes despite the overall decreased the incidence. Because certain proportion of S. pneumoniae is known to harbor chemo-resistance genes with reduced susceptibility to cephalosporin agents, caution is advised during initial treatment with ceftriaxone, which is often used. Thus, IPD prevention by vaccination is critical.

With the advent of PCVs, the incidence of IPD due to vaccine serotypes, most notably serotype 6B was drastically decreased. S. pneumoniae serogroup 6 comprises four different serotypes (6A- 6D). The incidence of a new S. pneumoniae serotype (genotype) 6E was recently reported [7]. Studies investigating the clinical and microbiological characteristics of S. pneumoniae serotype 6E are With the advent of PCVs, the incidence of IPD due to vaccine serotypes, most notably serotype 6B was drastically decreased. S. pneumoniae serogroup 6 comprises four different serotypes (6A- 6D). The incidence of a new S. pneumoniae serotype (genotype) 6E was recently reported [7]. Studies investigating the clinical and microbiological characteristics of S. pneumoniae serotype 6E are

Conclusion

Findings in the current study suggested that changes in S. pneumoniae serotypes responsible for pneumococcal disease in adults might be affected by pediatric PCV13 vaccination. Consequently, increase in the incidence of IPD due to non-vaccine serotypes, including 6E, following PCV13 worldwide remains a concern. Improvement of pneumococcal vaccine coverage for both pediatric and adult populations might be beneficial in preventing unwanted seroconversion in IPD.

References

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Citation: Takamatsu A, Noguchi M, Ito M, Matsuzaka S, Kawaguchiya M, Kobayashi N, et al. Serotype Changes in Adult Invasive Pneumococcal Disease in the Vaccine Era with Special Reference to Serotype 6E. Austin J Infect Dis. 2016; 3(2): 1027.

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