Maksuda Islam, Bangladesh

The rarity of serotype 19A among invasive pneumococcal disease (IPD) supported choice of PCV-10 for Bangladesh’s program. However, concern remains about emergence of this serotype, particularly multi-drug resistant (MDR) sequence type (ST) 320, after widespread PCV10 use. Therefore, we tracked the molecular epidemiology of 19A among pneumococci from Bangladeshi children over time.

Methods

We analyzed 64 isolates (54 pre-PCV and 10 post-PCV) spanning 2005-2018; isolates were from IPD (n=23), carriage (n=23) and otitis media (n=18). Isolates were subjected to whole genome sequencing and STs determined. Antimicrobial resistance patterns were determined phenotypically and genotypically.

Results

Overall, a total of 24 STs were identified, including 3 novel STs. Among the identified STs, ST12473 (16.4%), ST2464 (16.4%) and ST12891 (11.5%) were most common. No ST320 strains were detected. Multidrug resistance (erythromycin, co-trimoxazole and tetracycline) was only seen in ST12473. In addition, ST2464 was predominantly non-susceptible to co-trimoxazole and tetracycline.

Conclusions

The surveillance identified two drug resistant STs but not ST320. However, considering the increased rate of serotype 19A seen elsewhere following PCV7 and PCV10 use, we should continue surveillance and molecular investigation of this serotype.

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IMPACT OF 10-VALENT PNEUMOCOCCAL CONJUGATE VACCINE (PCV-10) ON PNEUMONIA HOSPITALIZATION RATE AMONG BANGLADESHI CHILDREN (ID 1134)

Session Name

Vaccines - Impact of Vaccine programs and Serotype Replacement

Presenter

Md Hasanuzzaman, Bangladesh

Authors

Abstract

Abstract

Background

Bangladesh introduced PCV-10 in March 2015 with a 3+0 schedule. We assessed impact of PCV-10 on pneumonia and severe pneumonia among children <5 years.

Methods

Children <5 years were enrolled following WHO’s Invasive Bacterial Vaccine Preventable Disease surveillance criteria. January 2011 to March 2015 was considered as baseline and April 2015 to June 2019 as post-PCV era. PCV-10 impact was measured based on hospitalization rate (adjusted with all hospitalized patients) of pneumonia and severe pneumonia using (I) WHO case definitions and (II) physician’s diagnosis.

Results

Analysis using WHO’s case definition didn’t show any significant changes in pneumonia admissions among those <5 years or 3-23 months. Similarly, no impact was noted for admissions of physician-diagnosed pneumonia. However, physician-diagnosed severe pneumonia episodes decreased 82% (95% CI: 78.9%-84.2%) from 4.5%-0.8% among those <5 years and 76.1% (95% CI 69.8%-81.2%) from 4.4 -1% among children 3-23 months.

Conclusions

The lack of significant change for WHO-defined pneumonia and severe pneumonia or physician-diagnosed pneumonia may be due to a lack of specificity in the definitions, including many illnesses not caused by pneumococcal infection. Reduction in severe pneumonia admissions (among which more cases are expected to be bacterial), suggests a role of PCV-10 in reduction of pneumococcal pneumonia.

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MOLECULAR EPIDEMIOLOGY OF PNEUMOCOCCUS ISOLATED FROM INVASIVE PNEUMOCOCCAL DISEASES BEFORE INTRODUCTION OF PCV-10 IN BANGLADESH, 2002-2015 (ID 1037)

Session Name

Basic Sciences - Genomics and Transmission

Presenter

Roly Malaker, Bangladesh

Authors

Abstract

Abstract

Background

Bangladesh has been generating pneumococcal data since last 30 years to make an evidence-based data for vaccine introduction. This study is aimed to make a genomic characterization of pneumococcus isolated from pre-vaccine period.

Methods

Whole-genome sequencing data of total 525 pneumococcus isolated from IPD, during 2002 to 2015, were analyzed using previously established methods.

Results

Overall, 57 serotypes were identified, and most predominant serotypes were 2, 1, 14, 23F, 5, 19F, 12A and 45 which accounted for 50% of isolates. Serotype coverage were 47% for PCV10+6A, 50% for PCV13 and 58% for PCV20. The population was genetically diverse with 108 known and 61 new Sequence Types (STs), encompassing in 89 GPSCs. Among them, GPSC96 (serotype 2, n=66, 11.6%), GPSC 2 (serotype 1, n=48, 9%), GPSC 9 (serotype 14, n=32, 6%) were most predominant. Significant increase in resistance has observed for Erythromycin (0%-60%). Resistance is commonly seen in GPSC 10, 43, 101 and 482 mainly among serotype 19F, 23F, 6B and 7B, respectively.

Conclusions

Pneumococcus in Bangladesh is diverse and different in respect of serotype, ST and GPSC. This data will work as the baseline population to monitor vaccine induced changes in molecular epidemiology.

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NASOPHARYNGEAL CARRIAGE OF STREPTOCOCCUS PNEUMONIAE SEROTYPES AMONG HEALTHY CHILDREN IN NORTH INDIA (ID 318)

Session Name

Clinical Sciences - Disease Burden in Infants, Children/Youth, and Adults

Presenter

Shally Awasthi, India

Authors

Abstract

Abstract

Background

Streptococcus pneumonia (SP) causes morbidity and mortality among children worldwide. India introduced 13-valent pneumococcal conjugate vaccine (PCV-13) in 2017. Current study was conducted to isolate SP from nasopharyngeal (NP) swabs of healthy children and assess changes in serotypes among PCV vaccinated and unvaccinated children.

Methods

Cross-sectional study was conducted (July-August 2019) in Lucknow District, North India. Children (2-59 months) who had no clear illness/hospitalization (last one-month) were recruited from vaccination-clinics of hospitals. After NP specimen collection, bacterial culture was done using 5% sheep agar-blood plate containing gentamicin. Pneumococcal isolates were identified by optochin-sensitivity and bile-solubility. Serotyping was done using Quellung Method

Results

Of 300 children, 56.7%(170/300) were males and 52.0%(156/300) were 2-11 months. Overall SP colonization rate was 37.6% (113/300). Vaccine serotypes isolated were 18C,19A,19F,23F,3,4,6A,6B,9V. Among 60% (181/300) PCV vaccinated, SP positivity was 37.5% (68/181) and vaccine serotype were 39.7% (27/68). Among 40% (119/300) non-PCV vaccinated-children, 37.8%(47/119)had NP colonization positive and PCV-13 serotypes were 37.7%(17/47). Non-Vaccine serotypes were 10A,15A,15B,15C,21,34,35B,22F and similar in vaccinated and unvaccinated children.

Conclusions

About 4 of 10 healthy children had NP colonization with SP and around 40% serotypes were covered by PCV-13. Our preliminary data suggests that SP colonization rate and serotype isolates were similar in vaccinated and unvaccinated children

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GLOBAL GENOMIC EPIDEMIOLOGY OF PNEUMOCOCCAL SEROTYPE 2 ISOLATED DURING 1989 TO 2019 (ID 1084)

Session Name

Basic Sciences - Genomics and Transmission

Presenter

Roly Malaker, Bangladesh

Authors

Abstract

Abstract

Background

Serotype 2 was a major cause of pneumococcal pneumonia about 100 years ago and then disappeared. Recently, serotype 2 re-emerged in many countries, including Bangladesh and associated with meningitis. This study aims to understand genomic and epidemiological characteristics of newly emerged serotype 2 strains.

Methods

Whole-genome sequencing was performed on 146 isolates (invasive= 125, carriage= 8 and other= 5, unknown= 8) collected between 1989 and 2017. Data were analyzed for comparative genomics, antimicrobial resistance and molecular typing.

Results

Isolates were from 16 countries, mostly in Asia (n=93), Africa (n=23) and Oceania (n=26). Bangladesh (n=66) and Papua New Guinea (n=26) contributed 63% of the isolates. Among the known clinical conditions, 80% (91/113) were from meningitis. All isolates belonged to GPSC96 lineage and descended from two predominant sequence types: ST74 found in Asia and Africa, and ST1504 found in Papua New Guinea and Israel. Almost all isolates were sensitive to all antibiotics. No significant genetic differences were detected between invasive and carriage isolates.

Conclusions

Our findings don’t explain why the recent increase in serotype 2 occurred but exclude an outbreak or emergence of an antimicrobial-resistant strain as the cause. These isolates have unusually high propensity to be invasive, mostly causing meningitis.

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EFFECT OF NATIONAL INTRODUCTION OF 10-VALENT PNEUMOCOCCAL CONJUGATE VACCINE ON INVASIVE PNEUMOCOCCAL DISEASES IN BANGLADESH: A POPULATION-BASED STUDY (ID 471)

Session Name

Vaccines - Impact of Vaccine programs and Serotype Replacement

Presenter

Abdullah H. Baqui, United States of America

Authors

Abstract

Abstract

Background

Bangladesh introduced 10-valent pneumococcal conjugate vaccine (PCV10) in its national immunization program in early 2015. We conducted case-control, incident trend and indirect cohort analyses to assess PCV impact on invasive pneumococcal diseases (IPD).

Methods

To assess PCV impact on IPD, we established community and facility-based surveillance in Bangladesh’s Sylhet district. Children 3-35 months of age attending study clinics were assessed for suspected IPD. Blood and CSF were collected from suspected IPD cases to isolate pneumococcus using culture and molecular tests. Community and clinic controls were matched to each IPD case. Data on immunization status and potential confounders were collected from cases and controls.

Results

During July 2015-June 2018, 94,584 children 3-35-month-old were under surveillance. Of these, 32,021 sought care from study clinics. We enrolled 44 IPD cases, 158 clinic and 173 community controls. Case-control analysis using clinic controls showed 89.6% (95% CI: -26.0 to 99.1) and using community controls showed 83.1% (95% CI:1.57 to 97.1) effectiveness in preventing vaccine type IPD. Time trend analysis estimated 80.1% (95% CI: 38.4, 93.6) effectiveness, and the indirect cohort analysis estimated 76.1% (95% CI: 17.3, 93.1) effectiveness with 3 doses of PCV.

Conclusions

PCV in our population is highly effective in preventing IPD.

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MACROLIDE RESISTANT STREPTOCOCCUS PNEUMONIAE: ASSOCIATION WITH SEROTYPE, SEQUENCE-TYPE (ST) AND ANTIBIOTIC CONSUMPTION (ID 1085)

Session Name

Clinical Sciences - Disease Burden in Infants, Children/Youth, and Adults

Presenter

Sharmistha Goswami, Bangladesh

Authors

Abstract

Abstract

Background

Azithromycin is a useful therapeutic, but its long half-life encourages development of azolide/macrolide resistance. We investigated increasing macrolide-resistance among Streptococcus pneumoniae, exploring the association of macrolide-resistance with serotype, clone and azithromycin use.

Methods

Between January-2002 to March-2015, 464 invasive pneumococcal isolates were collected and whole-genome sequenced. Azolide/macrolide non-susceptibility was determined by erythromycin disk-diffusion and E-test.

Results

We identified macrolide resistance in 70 (15%) pneumococci; 64% of which harbored ermB, 33% mefA and 1.4% carried both the genetic determinants. Few (n=6 of 265 tested) were identified through 2009; subsequently resistance increased to 46% in 2014, and 60% in 2015. Macrolide-resistant pneumococci exhibited 24 serotypes; 19F (14%), 6B (13%) and 23F (13%) were predominant. PCV10, PCV13, and PCV20 would address 51% (36/70), 56% (39/70), and 63% (44/70), respectively. Macrolide-resistant pneumococci belonged to 26 GPSCs and 42 STs. Dominant lineages were GPSC10 (ST1553, 12894, 14490, 14488), GPSC43 (ST4745, 3214), GPSC101 (ST2854, 1078) and GPSC482 (ST5612). Increased azithromycin consumption showed direct association with increasing macrolide-resistance during this period (r=0.8572, p=0.0031, Spearman correlation coefficient).

Conclusions

Serotype and genotype diversity among macrolide-resistant pneumococci and low proportion addressed by PCVs suggests that a vaccine covering all strains or restricted consumption of azithromycin is needed to reduce transmission of macrolide-resistant strains.

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EFFECT OF PCV-10 ON INVASIVE PNEUMOCOCCAL DISEASE AMONG BANGLADESHI CHILDREN (ID 1010)

Session Name

Vaccines - Impact of Vaccine programs and Serotype Replacement

Presenter

Md Hasanuzzaman, Bangladesh

Authors

Abstract

Abstract

Background

Bangladesh introduced PCV-10 in March 2015 using a 3+0 schedule. We evaluated PCV-10 effect on invasive pneumococcal disease (IPD) among children <5 years.

Methods

IPD surveillance is ongoing in four sentinel hospitals. Numbers of children with pneumococcus detected from a sterile site (IPD cases) were adjusted using number of febrile children tested with blood and/ CSF each year as the denominator. Data from pre-vaccine baseline (January 2012 to March 2015) and post-vaccine (April 2015 to September 2019) periods were compared to determine PCV-10 impact by age group. Serotypes in PCV-10 plus 6A were considered vaccine types (VT).

Results

We identified 543 children with IPD among 60,921 children tested during 2012 to September 2019. IPD rates among children <5 years decreased 61% (CI: 45.8-72.4%) between baseline (137/10,000 tested) and 2019 (53/10,000; Figure-A); VT IPD rates fell 71% (CI: 47.2-85.4%; 53 to 15/10,000). Among children 3-23 months, IPD declined 70% (CI: 54.9-81.9%) between baseline (207/10,000) and 2019 (63/10,000; Figure-B); VT rates dropped 87% [(CI: 65.2-96.5%); 81 to 10/10,000]. Nonvaccine-serotype IPD rates were stable. figure 1.png_modified.png

Conclusions

PCV-10 introduction resulted in large reductions of overall and VT IPD among young children. In contrast to reports from elsewhere, serotype replacement is not yet evident in Bangladesh.

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PNEUMOCOCCAL CARRIAGE AND SEROTYPE DIVERSITY AMONG HEALTHY ADULTS IN BANGLADESH (ID 1095)

Session Name

Vaccines - Impact of Vaccine programs and Serotype Replacement

Presenter

Sanchita K. Ritu, Bangladesh

Authors

Abstract

Abstract

Background

Streptococcus pneumoniae colonization in the nasopharynx (NP) of elderly reflects transmission in the community and disease risk. Few studies measured pneumococcal carriage among adults. However in developing countries, the data is scare. To address this, we conducted cross-sectional studies during October 2014-February 2015 and July-September 2015. As PCV-10 introduced in Bangladesh on March 2015, both periods are considered baseline data.

Methods

In Mirzapur, a rural area in Bangladesh, 1408 NP swabs were collected from healthy adults (age, 45-95 years) identified during demographic surveillance system household visits. Swabs were cultured for pneumococci and serotyped using quellung reaction.

Results

Pneumococcal colonization rates during the two time periods were 10% (80/762) and 9% (61/646), respectively. Fifty-one different serotypes were detected. Only 13% (19/141) of isolates were PCV-10 serotypes, 22% (31/141) were PCV-13, 33% (46/141) were PCV-20, and 34% (48/141) were 23-valent polysaccharide vaccine serotypes. The most predominant serotypes were 13 (8%), 34 (8%), 3 (6%), 39 (6%), 35B (4%), 18C (4%) and 19F (4%).

Conclusions

Our findings indicate that a diverse set of serotypes cause pneumococcal carriage among older adults in Bangladesh, with 4 of the 7 most predominant not found in existing or forthcoming conjugate vaccine formulations.

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