Mathuram Santosham, United States of America

Johns Hopkins University International Health and Pediatrics

Author Of 6 Presentations

 Conference Calendar

CHARACTERIZATION OF STREPTOCOCCUS PNEUMONIAE SEROTYPE 3 CARRIAGE AND DISEASE ISOLATES AMONG NATIVE AMERICANS IN THE SOUTHWEST UNITED STATES (ID 1020)

Session Name
Basic Sciences - Genomics and Transmission
Presenter
Authors

Abstract

Background

Despite inclusion in PCV13, Streptococcus pneumoniae serotype 3 (ST3) continues to cause significant morbidity and mortality. In Native American communities in the southwest US in 2015-2017, the ST3 carriage prevalence among children was 2.7% and the incidence of ST3 invasive pneumococcal disease (IPD) among adults was 9.0/100,000. An emerging lineage of ST3 belonging to Clonal Complex (CC) 180, termed clade II, has recently increased.

Methods

We analyzed the genomic epidemiology of 202 ST3 isolates collected from 133 adults and 69 children with carriage (n=71) or IPD (n=131) from 1999–2018. Using phylogenetics based on whole-genome sequencing data, we determined clade membership of each isolate and assessed how the population structure changed over time.

Results

The percent of isolates belonging to clade II increased from 22.3% (n=94) in 1999-2010 to 65.7% (n=108) in 2010-2018 (Figure A). Carriage isolates were comprised equally by three clades (CC180 clade Ia n=24 and II n=23 and non-CC180 n=24); however, IPD isolates were more likely to be clade II (1a n=37, II n=69, non-CC180 n=25; OR=2.32, 95% CI 1.27-4.25) (Figure B).

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Conclusions

Overall, we find that ST3 clade II has increased significantly since the introduction of PCV13 and is found more commonly in invasive disease compared to other clades.

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HEAD TO HEAD COMPARISONS AT 2, 4, AND 7 MONTHS, FOLLOWING STANDARD AND COMBINED PHID-CV10 AND PCV13 SCHEDULES. (ID 429)

Session Name
Vaccines - Pneumococcal Vaccines Development
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Abstract

Background

Australian Aboriginal children are at high risk of early infection withStreptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi). We evaluated immunogenicity against 10 shared serotypes of a 4-dose combination schedule of PHiD-CV10 at 1-2-4 months plus PCV13 at 6 months, compared with standard 2-4-6 month schedules.

Methods

Infants were allocated (1:1:1) at 28 to 38 days of age, to 3-dose schedules of PCV13 (P) or PHiD-CV10 (S) at 2-4-6 months (_PPP or _SSS), or a combination schedule at 1-2-4-6 months (SSSP). Immunogenicity was measured at 2, 4, and 7 months.

Results

At 2 months the SSSP combination was superior to pre-vaccination (VTs other than 6B, 19F, or 23F). At 4 months SSSP was superior to _PPP (9 VTs) and _SSS (7 VTs), and _SSS was superior to _PPP (8 VTs). At 7 months, SSSP was superior to _PPP (1, 6B, 9V, 19F and 23F) and _SSS (8 VTs), and _PPP was superior to _SSS (8 VTs). OPA supports the SSSP schedule, particularly against 1, 6B, and 23F.

Conclusions

The 1-2-4-6 month schedule (SSSP) was superior at 2, 4, and 7 months of age compared to _SSS or _PPP, particularly for 1, 6B, and 23F at 7 months. At 4 months, _SSS was superior to _PPP.

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DIFFERENCES IN PNEUMOCOCCAL CARRIAGE PREVALENCE BY TESTING METHOD AND SPECIMEN TYPE AMONG NATIVE AMERICAN INDIVIDUALS DURING ROUTINE USE OF 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE (PCV13) (ID 995)

Session Name
Clinical Sciences - Pneumococcal Infections in Aboriginal Populations
Presenter
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PCV INTERCHANGEABILITY: SYNTHESIZING AVAILABLE EVIDENCE TO INFORM PROGRAM SWITCHES BETWEEN PRODUCTS IN AN EXPANDING VACCINE PRODUCT LANDSCAPE (ID 1226)

Session Name
Population Sciences - Knowledge Translation and Public Health Policy
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INTERCHANGEABILITY OF PHID-CV10 AND PCV13 IN PRIMARY COURSE SCHEDULES (ID 204)

Session Name
Vaccines - Pneumococcal Vaccines Development
Presenter
Authors

Abstract

Background

In remote communities of northern Australia, we previously demonstrated that the onset of otitis media (OM) in Aboriginal infants was preceded by acquisition of bacterial pathogens that colonise the nasopharynx (NP) soon after birth. We aimed to determine safety and effectiveness of mixed vaccine schedules against early infection due to non-typeable Haemophilus influenzae and Streptococcus pneumoniae.

Methods

In an open-label controlled trial, we randomised (1:1:1) Aboriginal infants at 28 to 38 days of age, to either Prevenar13™ (P, PCV13) at 2-4-6 months of age (_PPP), Synflorix™ (S, PHiD-CV10) at 2-4-6 months (_SSS), or Synflorix at 1-2-4 months plus Prevenar13 at 6 months (SSSP). Primary outcomes (assessor-blinded) were immunogenicity at 7 months of age against pneumococcal serotypes 3, 6A, and 19A, and protein D (GMCs and proportions of infants with IgG > 0·35 µg/mL or > 100 EL.U/mL, respectively). Secondary immunogenicity outcomes at 2 and 4 months are also reported.

Results

A 4-dose early 1-2-4-6 month combination schedule of Synflorix plus Prevenar13 (SSSP) provided superior overall immune protection against serotypes 3, 6A, 19A, and protein D, compared to standard 3-dose 2-4-6 month schedules (_SSS or _PPP).

Conclusions

These vaccines can be combined safely and effectively within this primary schedule, with no evidence of immune suppression.

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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
Authors

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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