Successful Control of Streptococcus pneumoniae 19A Replacement With a Catch-up Primary Vaccination Program in Taiwan.

BACKGROUND: Streptococcus pneumoniae infections in Taiwan mostly occur in children aged 2-4 years. Because of a significant increase in the incidence of serotype 19A-related infections, the 13-valent pneumococcal conjugate vaccine (PCV13) was initially introduced in the national immunization program for children 2-5 years of age, prior to the national programs for infants. We have assessed the impact of such vaccination programs in reducing the incidence of invasive pneumococcal disease (IPD) in Taiwanese children. METHODS: We analyzed the national data on IPDs from the Taiwan Centers for Disease Control between 2008 and 2017. We calculated the incidence rates of IPD and incidence rate ratios (IRRs) between years for different serotypes to estimate the effectiveness of the vaccination programs. RESULTS: The national catch-up primary vaccination schedule successfully reduced the incidence rate of IPD from 17.8/100 000 in 2012 to 5.5/100 000 in 2017 among children aged 0-5 years. The IRR (2017 over 2012) was 0.31, corresponding to a 69% reduction. A modest herd effect was also observed, with a 37% reduction in the incidence of IPD in elderly people (≥70 years) from 2012 to 2017. The incidence of IPD caused by serotype 19A in children aged 0-5 years was reduced by 32.6-44.3% yearly from 2012 to 2017. In 2015, serogroup 15 outnumbered 19A, to become the leading serotypes in children 0-5 years old. CONCLUSIONS: Special catch-up vaccination programs starting from children 2-5 years of age with PCV13 have been highly effective in reducing the incidence of IPD, especially as caused by serotype 19A, in Taiwanese children.

Antimicrobial susceptibility testing of Bordetella pertussis in Taiwan prompted by a case of pertussis in a paediatric patient.

In Taiwan, pertussis is a notifiable disease with a low incidence in recent years, and antimicrobial susceptibility testing for the causative agent, Bordetella pertussis, has not been reported to date. In May 2007, the Centers for Disease Control, Taiwan, was informed of a 1-month-old pertussis patient who did not respond to erythromycin treatment. In this study, we report the result of antimicrobial susceptibility testing performed for the suspected erythromycin-resistant isolate, as well as for an additional 27 B. pertussis clinical isolates that represented almost all epidemiologically unrelated isolates obtained throughout Taiwan between 2003 and 2007. All isolates were fully susceptible to azithromycin, erythromycin, clarithromycin and trimethoprim/sulfamethoxazole (MIC < or =0.047 mug ml(-1)). This result demonstrates the general susceptibility of B. pertussis to antimicrobial agents in vitro in Taiwan.

Low rate of nasopharyngeal carriage and high rate of ampicillin resistance for Haemophilus influenzae among healthy children younger than 5 years old in northern Taiwan.

BACKGROUND AND PURPOSE: Surveillance data of colonization by Haemophilus influenzae in Taiwan are lacking. This study aimed to define the nasopharyngeal carriage rate of H. influenzae among children younger than 5 years in northern Taiwan, and to determine the antibiotic susceptibility, serotype and the clonal relationship of these isolates. METHODS: Nasopharyngeal specimens were obtained from 511 healthy children younger than 5 years. All H. influenzae isolates were serotyped. The minimal inhibitory concentrations for various antibiotics were determined. Pulsed-field gel electrophoresis (PFGE) was used for clonal analysis. RESULTS: Among 511 children, 269 (52.6%) had been vaccinated with at least one dose of H. influenzae type b (Hib) conjugate vaccine, 236 (46.2%) were unvaccinated and 6 (1.2%) had no vaccination records available. Twenty six H. influenzae strains were isolated. There were three Hib isolates and the others were nontypeable H. influenzae (NTHi). The carriage rate for Hib was 0.6% (3/511) and of NTHi was 5% (23/511). Three (1.27%) of the 236 unvaccinated children were carriers of Hib, whereas none of the 269 vaccinated children carried Hib. Two out of the three Hib isolates and 14 (60.9%) of 23 NTHi isolates were ampicillin-resistant. Multidrug resistance was found in 7 (26.9%) of the isolates. Among the isolates, 61.5% were beta-lactamase producers; there were no beta-lactamase-negative ampicillin-resistant isolates. The PFGE restriction patterns showed a wide diversity of genotypes. CONCLUSIONS: There is very low nasopharyngeal carriage of Hib among children younger than 5 years in northern Taiwan. This may explain why the incidence of invasive Hib disease is also low in Taiwan. In addition, we found a high prevalence of beta-lactamase-positive ampicillin-resistant nasopharyngeal H. influenzae isolates.

Molecular epidemiology of group A streptococcus causing scarlet fever in northern Taiwan, 2001-2002.

In this study, 830 Streptococcus pyogenes isolates collected between 2001 and 2002 from patients with scarlet fever in northern Taiwan were analyzed by M protein gene (emm) sequence typing, pulsed-field gel electrophoresis (PFGE), and antimicrobial susceptibility testing. A total of 21 emm types and 56 PFGE patterns were identified. The most frequent emm types were emm1 (29.2%), emm4 (24.1%), emm12 (19.0%), emm6 (15.8%), stIL103 (5.7%), and emm22 (1.9%). Antimicrobial resistance profiles were determined, and resistance to erythromycin (24.6%), clindamycin (2.0%), and chloramphenicol (1.3%) was detected. Five major emm types (emm4, emm12, emm1, emm22, and emm6) accounted for 95.6% of the erythromycin-resistant isolates. The decreased prevalence of erythromycin-resistant emm12 strains coincided with the overall decrease in erythromycin resistance from 32.1% in 2001 to 21.1% in 2002 in Taiwan. Five major clones (emm4/2000, emm12/0000, emm4/2010, emm1/1000, and emm22/8100) represented 72.1% of the erythromycin-resistant isolates. The survey of group A Streptococcus emm types, genetic diversity, and antibiotic resistance has direct relevance to current antimicrobial use policies and potential vaccine development strategies.

Epidemiological shift in the prevalence of pertussis in Taiwan: implications for pertussis vaccination.

In Taiwan, routine pertussis immunization has been implemented for more than 40 years and a low incidence of pertussis was maintained until an 80-fold increase in cases occurred in 1992. The unexpected increase emphasized the significance of pertussis. This study evaluated a total of 2452 reported cases of pertussis during 1993-2004 and surveillance data on incidence, age distribution and seasonality. The highest morbidity was in infants aged <1 year, and upward trends in the incidence of pertussis were significant for infants aged <1 year and adolescents aged 10-14 years. The highest mean number of cases was observed in August and upward trends were in colder months. This study indicates that the epidemiology of pertussis may have been changed by waning immunity in Taiwan. Increased surveillance activities, especially in older age groups, and additional booster doses of acellular pertussis vaccine for children aged 6-8 years and adolescents/young adults aged 15-20 years are necessary to control and prevent pertussis.

Molecular epidemiology of Bordetella pertussis in Taiwan, 1993-2004: suggests one possible explanation for the outbreak of pertussis in 1997.

Pertussis reemerges periodically despite high pertussis vaccination coverage in many countries. We used prn and fim3 gene sequences and pulsed-field gel electrophoresis (PFGE) to analyze the molecular epidemiology of 168 clinical isolates of Bordetella pertussis during 1993-2004, and deduced possible reasons for an outbreak in 1997 in Taiwan. In Taiwan, during 1996-1997, a shift of prn1 to prn2 was reflected in a transition of PFGE group I to group IIIa; during 2000-2001, the change from fim3A to fim3B was displayed in transition of PFGE group IIIa to group IIIb. These changes were also consistent with the two peaks of pertussis incidence in 1997 and 2000. In 1997, a larger than expected increase in the incidence of pertussis occurred and isolates were characterized by complicated pulsotypes, appearance of many new profiles and an unusual presence of prn3. Based on a high resemblance of PFGE profiles and the same virulence genes, a similar shift of circulating strains was observed in European countries as well as Taiwan; thus, the high incidence of pertussis in 1997 may be due to an international expansion of B. pertussis strains from a similar source. This study provides further elucidation of the global molecular epidemiology of B. pertussis.

Antimicrobial resistance patterns and serotype distribution of invasive Streptococcus pneumoniae isolates from children in Taiwan from 1999 to 2004.

Streptococcus pneumoniae causes substantial morbidity and mortality worldwide. Because only limited data are available for the antibiotic resistance patterns and seroepidemiology of invasive S. pneumoniae isolates in Taiwanese children, this national surveillance of invasive pneumococcal infections in children was conducted during a 5-year period. Invasive isolates of S. pneumoniae were obtained from sterile sites (yielding blood and cerebrospinal, pleural, and intra-articular fluids) in children (aged < or =14 years) at a total of 40 regional hospitals and medical centers distributed throughout Taiwan. The collection period was between July 1999 and June 2004, with a total of 286 isolates (including 30 cerebrospinal fluids) collected. All the samples were sent to the Center for Disease Control in Taipei for serotyping and susceptibility testing. Of the 286 S. pneumoniae isolates studied, the 5 most common serotypes were 14 (28.3%), 23F (21.0%), 6B (17.1%), 19F (13.6%), and 3 (4.9%). Intermediate- and high-level penicillin resistance was determined for 50.7% and 25.5% of the isolates, respectively. Isolate resistance was demonstrated to erythromycin (93%), tetracycline (82.2%), trimethoprim/sulfamethoxazole (79.4%), cefotaxime (11.2%), and levofloxacin (0.3%). Multiple drug resistance was found for each serotype, but mostly in types 14, 23F, 6B, and 19F. Overall, 85.0% of the serotypes, 90.8% of the penicillin-nonsusceptible S. pneumoniae (PNSSP), and 90.1% of the multiple drug-resistant (MDR) isolates were covered by the heptavalent pneumococcal conjugated vaccine (PCV7). In this study, we found a diverse pulse-field gel electrophoresis pattern among MDR isolates: a high prevalence of drug resistance and a continued increasing trend in penicillin resistance among nationwide pneumococcal isolates from children in Taiwan. The highest prevalence of invasive pneumococcal disease was in children aged 2 to 5 years, and the highest PNSSP prevalence and highest PCV7 coverage were in children aged <2 years. In terms of reducing the risk of invasive pneumococcal illness in Taiwan, the use of PCV7 is likely to have a beneficial effect similar to that obtained in countries that have used it.

Surveillance of invasive Streptococcus pneumoniae in Taiwan, 2002-2003.

A total of 522 Streptococcus pneumoniae invasive isolates from diverse sources were collected from January 2002 to December 2003 in Taiwan in order to understand the serotype distribution of invasive isolates in Taiwan. The most frequently isolated serotypes of S. pneumoniae were types 14 (18.4%), 23F (15.1%), 3 (13.8%), 19F (13.4%), 6B (8.2%), 9V (3.6%) and 4 (2.5%). The majority of cases were either under 5 years of age (24.1%) or older than 65 years (36.6%). Serotype distribution in adults aged over 14 years and children aged under 2 years was similar, except for that of type 3, which was more prevalent in adults. Penicillin-non-susceptible strains accounted for 67.7% of all strains and were the predominant strains of serotypes 23F, 19F, 6B and 14. Most strains were susceptible to cephem drug, 85.7% of isolates were susceptible to cefotaxime and 92.9% were susceptible to ceftriaxone. A total of 72.6% (379/522) of the isolates were resistant to at least two antibiotics. The 23-valent vaccine in the current commercial market would cover 87.2% of the serotypes and 100% of the penicillin-non-susceptible serotypes of S. pneumoniae in Taiwan. The coverage of 7- and 11-valent protein conjugate vaccines of the serotypes in children under 2 years of age would be 78.8 and 86.5%, respectively. These results will help to assess the adequacy of the vaccine formulations marketed in Taiwan.

National surveillance of invasive pneumococcal diseases in Taiwan, 2008-2012: differential temporal emergence of serotype 19A.

INTRODUCTION: Serotype replacement after the introduction of seven-valent pneumococcal conjugate vaccine (PCV7) and the future availability of multivalent PCVs prompted the listing of invasive pneumococcal disease (IPD) as a notifiable disease in Taiwan in October 2007. Here, we report the national surveillance results. METHODS: The study population comprised the whole nation of Taiwan from 2008 to 2012. Restricting to cases with viable isolates, we calculated the incidence, case fatality ratio, prevalence of serotype 19A, and percentage of vaccine preventable IPD. RESULTS: 3659 cases of IPD were identified yielding an incidence of 3.2 per 100,000 population; the highest incidence was among children aged 2-4 years (21.1 per 100,000 population). The case fatality ratio was 9.2% and the highest ratio was among adults aged ≥75 years (19.0%). The percentage of PCV7 preventable IPD decreased for all age groups, especially sharply among children aged 2-4 years, from 65.8% in 2008 to 12.9% in 2012. The prevalence of serotype 19A increased from 5.5% in 2008 to 25.3% in 2012 among all Streptococcus pneumoniae, displaying a differential temporal emergence among different age groups. Serotype 19A became the most prevalent serotype among children aged <2 years in 2009, children aged 2-4 and 5-17 years in 2010, and adults aged 18-49 years in 2012. CONCLUSIONS: The incidence of IPD fluctuated during the study period, with ongoing decrease due to PCV7 vaccine serotypes and increase due to non-vaccine serotypes. Serotype 19A became the most prevalent serotype in 2010 among all S. pneumoniae.

Antigenic divergence of Bordetella pertussis isolates in Taiwan.

In recent studies, antigenic divergence has been observed in Bordetella pertussis circulating isolates. We collected 80 Bordetella pertussis isolates in Taiwan from 1998 to 2004 and analyzed them using a combination of pulsed-field gel electrophoresis (PFGE) and sequencing of the ptxS1 and prn genes. The incidence of pertussis increases every 3 years, and most of the isolates prevalent since 1998 have expressed nonvaccine ptxS1A and prn2 alleles. Through PFGE analysis, all isolates could be classified into four major groups, and the incidence of these groups exhibited a correlation with the prn allele expressed by the isolates. We found that PFGE is more discriminative than gene sequencing, since it could divide the isolates expressing the prn2 allele into two groups: one group circulating from 1998 to 2001 and another group circulating from 2001 to 2004. The transition between the two groups in 2000 coincided with an outbreak of 326 cases. This research indicates that the antigenic divergence of B. pertussis circulating isolates has evolved over time in Taiwan. Such information will have implications for vaccine policy in Taiwan.