Invasive Pneumococcal Strain Distributions and Isolate Clusters Associated With Persons Experiencing Homelessness During 2018

Abstract

Background.

We aimed to characterize invasive pneumococcal disease (IPD) isolates collected from multistate surveillance in the United States during 2018 and examine within-serotype propensities of isolates to form related clusters.

Methods.

We predicted strain features using whole genome sequencing obtained from 2885 IPD isolates obtained through the Center for Disease Control and Prevention’s Active Bacterial Core surveillance (ABCs), which has a surveillance population of approximately 34.5 million individuals distributed among 10 states. Phylogenetic analysis was provided for serotypes accounting for ≥27 isolates.

Results.

Thirteen-valent pneumococcal conjugate vaccine (PCV13) serotypes together with 6C accounted for 23 of 105 (21.9%) of isolates from children aged <5 years and 820 of 2780 (29.5%) isolates from those aged ≥5 years. The most common serotypes from adult IPD isolates were serotypes 3 (413/2780 [14.9%]), 22F (291/2780 [10.5%]), and 9N (191/2780 [6.9%]). Among child IPD isolates, serotypes 15BC (18/105 [17.1%]), 3 (11/105 [10.5%]), and 33F (10/105 [9.5%]) were most common. Serotypes 4, 12F, 20, and 7F had the highest proportions of isolates that formed related clusters together with the highest proportions of isolates from persons experiencing homelessness (PEH). Among 84 isolates from long-term care facilities, 2 instances of highly related isolate pairs from co-residents were identified.

Conclusions.

Non-PCV13 serotypes accounted for >70% of IPD in ABCs; however, PCV13 serotype 3 is the most common IPD serotype overall. Serotypes most common among PEH were more often associated with temporally related clusters identified both among PEH and among persons not reportedly experiencing homelessness.

Following sequential introduction in the United States during the past 2 decades of 2 multivalent vaccines targeting common pneumococcal capsular serotypes [1, 2], there are additional opportunities to prevent a substantial disease burden through vaccination of adults. During 2018 there were 3297 documented cases of invasive pneumococcal disease (IPD) within the Centers for Disease Control and Prevention’s (CDC) Active Bacterial Core surveillance (ABCs) population of 34 460 237, and 71.2% of these cases occurred in adults ≥50 years of age [3].

Here we assess serotype and antimicrobial profile distributions of strains causing IPD during 2018 and quantitate genetic clustering within individual serotypes. During 2018, IPD due to the conjugate vaccine serotype 4 in 3 western ABCs areas was 100- to 300-fold higher among persons experiencing homelessness (PEH) than in other individuals in these areas [4]. Here we describe that the highest percentages of clustering isolates were found within serotype 4 and 3 additional serotypes highly associated with PEH.

MATERIALS AND METHODS

Isolates

The ABCs IPD cases were defined through pneumococcal isolation from a normally sterile site in a surveillance-area resident. ABCs areas covered entire states or select counties in 10 states during 2018 and are described elsewhere [3]. For PEH population estimates, we used US Department of Housing and Urban Development point-in-time count data to enumerate populations of PEH in ABCs sites [5]. We characterized 2885 isolates, which represented 87.5% of the IPD cases reported in 2018. ABCs categorized patients as PEH if documented in medical charts as homeless or residing in a shelter, medical respite, or church community center.

ABCs activities were determined by CDC human research protection procedures to be nonresearch, public health surveillance. Institutional board review and informed consent were not required.

Genomic Sequencing and Bioinformatics

Validated whole genome sequencing (WGS)–based methods [6–9] were used to predict features (Supplementary Table 1) for all isolates [10, 11], including capsular serotype, multilocus sequence type, presence/absence of 2 pilus types, and known resistance determinants with associated predicted minimum inhibitory concentrations (MICs).

Isolates were categorized as recently emerged serotype-switch variants based on serotype/clonal complex (CC) associations as described previously [10, 11].

Single-nucleotide polymorphisms (SNPs) were determined for genomes within each serotype representing ≥27 isolates employing kSNP3.0 with a kmer size of 19 [12], following which pairwise comparisons were generated employing Mega7 [13]. Phylogenetic trees were generated using Mega7 from core genomic matrices created from kSNP3.0 with the maximum likelihood method based upon the general time-reversible model.

National Center for Biotechnology Information accession numbers are provided for genomes that yielded minimal acceptable values for N50 (>10 000 bp) (Supplementary Table 1) and <700 contigs.

Quality Control for Predicting Serotypes and MICs

The 386 isolates recovered from Minnesota during 2018 were subjected to conventional serotyping and MIC testing, and results were compared to bioinformatics pipeline predictions.

There were 4 serotype discrepancies, 2 of which were due to initial error in Quellung-based testing (Supplementary Table 2). Of 3860 MIC comparisons (Supplementary Table 3; 386 isolates, 10 antimicrobials), there were 30 discrepancies relevant to clinical guidelines [14]; however, 27 of these differed by a single dilution (doubling) and were in “essential agreement” [15].

RESULTS

Year 2018 IPD and Serotype Distributions

During 2018, pediatric IPD due to 13-valent pneumococcal conjugate vaccine (PCV13) + 6C serotypes was primarily restricted to serotypes 3 and 19F (19/23 isolates) with the remainder due to serotypes 6C, 19A, and 18C. The 2 serotype 6C isolates represented recurrent episodes (5 months apart) in the same child and differed by 5 SNPs. Serotypes 3 (11 isolates) and 15BC (18 isolates; 15B and 15C combined) were most frequent among the <5-year age group, with 6 additional serotypes accounting for 5–10 isolates each. CCs associated with each serotype are depicted in Figures 1 and 2 as assigned (Supplementary Table 1).

Figure 1.

Active Bacterial Core surveillance serotype distribution among individuals aged <5 years. The primary clonal complex (blue) indicated for each serotype corresponds to the single most commonly occurring clonal complex listed in Supplementary Table 1. Serotype “15D” is a putative newly discovered serotype highly related to serotypes 15A and 15F, based upon a unique serologic profile and cps locus composition (B. Beall, unpublished data).

Figure 2.

A, Active Bacterial Core surveillance (ABCs) serotype distribution among individuals aged ≥5 years. The primary clonal complex (CC; blue) indicated for each serotype corresponds to the single most commonly occurring CC listed in Supplementary Table 1. B, ABCs serotype distribution among persons experiencing homelessness. The primary CC (blue) indicated for each serotype corresponds to the single most commonly occurring CC listed in Supplementary Table 1. C, Numbers of isolates within each serotype sharing ≤10 single-nucleotide polymorphisms with at least 1 other isolate within entire sampling of serotype (90%–100% of all isolates within each serotype). Number is percentage of isolates within total isolate comparison. Abbreviations: PEH, people experiencing homelessness; PNEH, people not experiencing homelessness.

Of the 2885 isolates characterized from 2018, 2780 (96.4%) were from individuals ≥5 years old (Figure 2A). These isolates represented 40 different serotypes, with 13 occurring in ≤8 isolates. During 2018, PCV13 + 6C serotypes accounted for 819 of 2780 (29.5%) isolates from those aged ≥5 years (Figure 2A).

Serotypes 3, 22F, and 9N were the most common IPD serotypes during 2018 (Figures 1 and 2A), accounting for 841 of 2885 (29.2%). The 23 remaining serotypes each represented 34–144 isolates.

Serotype Distributions of Isolates From PEH

Of the 2885 IPD isolates, 2823 (97.9%) were from individuals of known residence status. Of these isolates, 198 (7.0%) were from PEH. Of these 198 isolates, 149 (75.3%) were recovered from the 4 states California, Colorado, Oregon, and New Mexico, which also had the highest ratios of PEH/non-PEH isolates (58/241, 56/235, 18/144, and 17/246, respectively) (Supplementary Figure 1).

Serotypes 4, 12F, 20, and 7F had the most disproportional representation from PEH (compare Figure 2A and 2B). These 4 serotypes accounted for 87 of 198 (43.9%) isolates from PEH (Figure 2B) and 253 of 2687 (9.4%) remaining isolates. IPD among PEH accounted for 36 of 105 (34.3%) serotype 4 cases, 27 of 97 (27.8%) serotype 12F cases, 15 of 101 (14.9%) serotype 20 cases, and 9 of 37 (25.7%) serotype 7F cases. Of the 340 cases caused by these 4 serotypes, all but 2 serotype 12F cases were among adults (average age 46 years), and 87 isolates (25.6%) were from PEH.

All 36 serotype 4 cases among PEH were from 3 ABCs sites: Colorado (Denver area, n = 16), California (San Francisco area, n = 13), and New Mexico (n = 7); 103 of the 105 total serotype 4 isolates were recovered from these 3 sites. The highest increase of serotype 4 IPD cases during 2018 was in Colorado, followed by California and New Mexico [4]. The majority of IPD cases caused by serotypes 20 and 12F among PEH were also within these same 3 ABCs sites (13/15 and 25/27 isolates for serotypes 20 and 12F, respectively). Serotype 7F isolates from PEH were restricted to California (4 isolates) and Oregon (5 isolates).

Phylogenetic Clustering Within Serotypes

Genetic clustering within the 26 most common serotypes was measured by pairwise SNP comparisons between genomes of adequate sequence quality within each serotype (90%–100% of isolates). Cluster isolates were defined by sharing ≤10 SNPs with at least 1 other isolate within the serotype. Serotypes 4, 12F, 20, and 7F, which had the highest proportions of isolates from PEH, also had the greatest proportions of isolates (61.6%–88.0%) within related clusters (Figures 2B and 2C). Three of these 4 serotypes displayed little fluctuation in incidence or clustering during 2015–2018; however, serotype 4 showed obvious increased incidence and clustering [4]. The number of serotype 4 isolates increased approximately 3-fold during 2015–2018.

Within each of these 4 serotypes, there were multiple instances of distinct phylogenetic branches encompassing clusters of apparently highly temporally related isolates. These clusters were often comprised of isolates from both PEH and persons not experiencing homelessness (PNEH) (Figures 3–6). In each instance, highly related subclusters were phylogenetically segregated to the same ABCs site, and often to the same county.

Figure 3.

Phylogenetic analysis of serotype 4 isolates. The tree with the highest log likelihood (−73 581.17) is shown. Initial tree(s) for the heuristic search were obtained automatically by applying neighbor-joining and BioNJ algorithms to a matrix of pairwise distances estimated using the maximum composite likelihood approach, and then selecting the topology with superior log likelihood value. The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. The analysis involved 100 nucleotide sequences. There was a total of 12 968 positions in the final dataset. Isolates from people experiencing homelessness (PEH) are indicated in red font. Isolates sharing ≤5 single-nucleotide polymorphisms (SNPs) with neighboring isolates are shaded. Predicted antimicrobial resistance is shown below each isolate (ery, erythromycin resistant; cli, clindamycin resistant; cot, cotrimoxazole resistant; cotI, intermediately cotrimoxazole resistant; tet, tetracycline resistant [predictive pipeline features for each resistance provided for each isolate in Supplementary Table 1]). ABCs sites are color coded in lines below the tree with county also indicated for each isolate as coded below. The relevant counties are indicated below each of the 5 relevant Active Bacterial Core surveillance (ABCs) sites with total number of year 2018 isolates indicated from people not experiencing homelessness (PNEH) and PEH and within each county. The ABCs sites include the 5 indicated Colorado (CO) Denver area counties and the 3 indicated California (CA) San Francisco Bay area counties. The entire states of New Mexico (NM) and Minnesota are included in ABCs as well as the 6-county Maryland area. Relative locations of the relevant (red font) CO, CA, and NM counties are indicated at right.

Figure 6.

Phylogenetic analysis of serotype 7F isolates. The tree with the highest log likelihood (−56 624.18) is shown. Initial tree(s) for the heuristic search were obtained automatically by applying neighbor-joining and BioNJ algorithms to a matrix of pairwise distances estimated using the maximum composite likelihood approach, and then selecting the topology with superior log likelihood value. The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. The analysis involved 34 nucleotide sequences. There was a total of 11 050 positions in the final dataset. Figure features and abbreviations are as described for Figures 3 and 4.

Within serotype 4, tight isolate clusters were evident within each major branch (Figure 3). Sequence type (ST) 244 and ST695 are 3 locus variants and comprise the long-standing serotype 4/CC244 [16]. ST10172 was the most abundant serotype 4 genotype. The ST10172 serotype-switch genotype (category 18 in Supplementary Table 4) was restricted to highly related isolates within Colorado and New Mexico, with the exception of 1 California isolate (Figure 3). Two 3-isolate clusters were restricted to PEH, 1 within the ST244 branch and 1 ST14038 cluster. CC244 lineages were restricted to California, with the exception of 4 isolates, including 2 closely related isolates recovered in Colorado (1 from PEH).

Twenty-five of the 27 serotype 12F isolates from PEH were recovered in Colorado (11), California (11), and New Mexico (3). Two nearly identical isolates of 12F/ST11595 were recovered from PEH in Tennessee (Figure 4). ST220 and ST218 are single-locus variants that have long comprised most serotype 12F IPD within ABCs [16]. The ST220 branch showed wider geographic distribution than ST218 and contained several highly related site-specific subclusters. The ST218 branch encompassed more related subclusters than the ST220 branch, as well as the majority of serotype 12F isolates from PEH. Isolates within the ST220 branch were mef positive (erythromycin resistant), whereas ST218 isolates were erythromycin susceptible.

Figure 4.

Phylogenetic analysis of serotype 12F isolates. The tree with the highest log likelihood (−73 581.74) is shown. Initial tree(s) for the heuristic search were obtained automatically by applying neighbor-joining and BioNJ algorithms to a matrix of pairwise distances estimated using the maximum composite likelihood approach, and then selecting the topology with superior log likelihood value. The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. The analysis involved 94 nucleotide sequences. There was a total of 12 659 positions in the final dataset. Figure features and abbreviations are as described for Figure 3. Active Bacterial Core surveillance (ABCs) surveillance areas for Colorado, California, New Mexico, Minnesota, and Maryland are described in the Figure 3 legend. ABCs areas also include Connecticut (entire state) and selected counties of Tennessee, Georgia, Oregon, and New York [3].

Thirteen of the 15 serotype 20 isolates from PEH were restricted to Colorado, New Mexico, and California, with single isolates from PEH recovered in Maryland and Tennessee (Figure 5). CC1257 accounted for all isolates except for a mixed (PEH and PNEH) pair of related (8 SNPs) serotype-switch variant isolates (CC568, category 83 in Supplementary Table 4). Highly related clusters of isolates were subdivided among 3 branches of CC1257, with the majority within the ST235 branch.

Figure 5.

Phylogenetic analysis of serotype 20 isolates. The tree with the highest log likelihood (−51780.06) is shown. Initial tree(s) for the heuristic search were obtained automatically by applying neighbor-joining and BioNJ algorithms to a matrix of pairwise distances estimated using the maximum composite likelihood approach, and then selecting the topology with superior log likelihood value. The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. The analysis involved 99 nucleotide sequences. There was a total of 10 234 positions in the final dataset. Figure features and abbreviations are as described for Figures 3 and 4.

All 9 serotype 7F isolates recovered from PEH were of the longstanding 7F/ST191 lineage (Figure 6) [16] and were restricted to Oregon (all 5 comprised mixed clusters with isolates from PNEH) and California (2 of 4 isolates were in mixed clusters).

Clustering of IPD Isolates From Long-term Care Facilities

Of the 2885 isolates characterized, 84 (2.9%) were from residents of long-term care facilities (LTCFs). Twelve of these 84 isolates were each highly related (differing by only 2–10 SNPs) to 1–4 isolates from individuals not residing in LTCFs (Supplementary Table 6). We found 2 highly related isolate pairs recovered from individuals 73–88 years of age within the same LTCFs (11A/ST62 isolates differing by 2 SNPs and 6C/ST473 isolates differing by 1 SNP).

Lineages With Elevated Penicillin MICs

Different patterns of MICs for penicillin, erythromycin, and clindamycin were characteristic of each serotype (Figure 7). Of the 2885 isolates, 531 (18.4%) had predicted penicillin MICs of ≥0.12 μg/mL, the cutoff for meningitis infections [14]. Among the 169 isolates with penicillin MICs ≥2 μg/mL, which were primarily 35B (104 isolates) and 19A (38 isolates), 152 were macrolide-resistant (100 mef positive; 52 were additionally clindamycin resistant and ermB positive). Among these 169 isolates, there were 40 isolates with predicted penicillin MICs of ≥4 μg/mL, the cutoff for nonmeningitis infections [14], 34 of which were 19A/CC320 (Supplementary Table 5). The 27 remaining isolates of serotypes other than 35B or 19A with penicillin MICs ≥2 μg/mL included 14 of PCV13 + 6C serotypes consisting of 4 19F/CC320 strains (3 with penicillin MIC = 4 μg/mL; Supplementary Table 5), 2 unrelated serotype 14 strains, 4 9V/CC156 strains, 2 unrelated 6C strains, a single 6B/CC90 strain, and a single serotype 3/CC320 serotype-switch variant. The latter strain was the third such isolate recovered within ABCs since 2015 (Supplementary Table 4) within 2 different states. There were 13 strains of non-PCV13 + 6C serotypes with penicillin MICs ≥2 μg/mL. These included 3 11A/CC156 switch variants, and 3 of the putative switch variant lineage 15B/CC3280 (Supplementary Table 4). Two of the 15B/CC3280 isolates had a penicillin MIC of 4 μg/mL (Supplementary Table 5). There were 6 serotype 15A isolates with penicillin MICs ≥2 μg/mL, 5 of which were of the common 15A/CC63 complex. A single serotype 9N strain had a penicillin MIC of 2 μg/mL. Pilus type 1 was highly associated with penicillin MICs ≥2 μg/mL (152/169 [89.9%]) [6, 10, 11].

Figure 7.

Combined minimum inhibitory concentration phenotype distributions for penicillin, erythromycin, and clindamycin within each serotype for year 2018 Active Bacterial Core surveillance pneumococcal isolates predicted from bioinformatics pipeline data. Cumulative data from each isolate are included in Supplementary Table 1. Abbreviations: cliR, clindamycin-resistance; eryR, erythromycin-resistance; pen, penicillin-resistance.

Within the 4 highly clustering serotypes disproportionally associated with PEH, there was only a single-serotype 12F outlier isolate (see ST3774 in Figure 4) with a penicillin MIC >0.03; however, multiple isolates within serotypes 4, 12F, and 7F were nonsusceptible to 1 or more of the antimicrobials cotrimoxazole, erythromycin, and clindamycin.

Macrolide Resistance

Macrolide resistance was evident in 839 of 2885 (29.1%) isolates, primarily conferred by ermB and/or mef. Of these 839, 263 (9.1%) were additionally clindamycin resistant, conferred by ermB (256 isolates) and 23S ribosomal RNA gene substitutions (5 isolates with A2061G, 2 with A2061C). Twenty-four serotype 3 isolates contained an ermB allele (ermB*), which encodes the G41E substitution [7] and was associated with low-level erythromycin resistance (0.5–1 μg/mL) in 17 isolates, but not with clindamycin resistance.

Other Resistance Features

Two levofloxacin-resistant 19A/CC320 strains were multiresistant (Supplementary Table 5). There were 2 highly related rifampin-resistant serotype 22F isolates (Supplementary Table 1). Chloramphenicol resistance was predicted for 58 isolates (cat positive) and tetracycline resistance in 346 isolates (tetM positive). Cotrimoxazole resistance was predicted in 561 isolates (19.4%) due to folA and/or folP mutations [7].

Recently Emerged Serotype-Switch Variants

Using previously employed nomenclature [10, 11], we observed 31 recently identified (within post–7-valent pneumococcal conjugate vaccine [PCV7] years) serotype-switch variants within 19 different serotypes (Supplementary Table 4). Fourteen of these variants were newly identified among year 2018 isolates (categories 75–88 in Supplementary Table 4). Notable are penicillin-resistant serotype 3 and 11A isolates (categories 44 and 11) that are normally penicillin susceptible. Category 18 showed the most increase of switch variant isolates, with the year 2018 total greater than the total from years 2015–2017. This serotype 4/CC439 variant (primarily ST10172) has emerged within Colorado and New Mexico, with disproportionate incidence within PEH (Figure 3A).

DISCUSSION

A main purpose of this “snapshot” of year 2018 IPD strains was to examine the frequency of isolates forming temporally related clusters within individual serotypes. The 4 serotypes displaying the most clustering were subsequently found to have the highest proportions of cases from PEH. The capacity of these 4 serotypes to disproportionally affect PEH and efficiently spread is likely multifactorial but could be related to naturally high transmissibility and invasive potential [17]. Our data suggest a transmission reservoir among adults, since these 4 serotypes were not recovered from younger individuals, and post-PCV13 carriage of these serotypes by children is rare [18]. Other studies have reported increased serotype 4 outbreaks among PEH compared to PNEH during post-PCV7 years [19–21]. Serotype 12F/CC220 is well known as a cause of outbreaks among disadvantaged people [22–24]. Serotypes 4 and 12F had the highest IPD occurrences among PEH in ABCs during 2018, despite being 11th and 13th overall in incidence, respectively. There are also many potential host-related factors that have undoubtedly influenced the spread of IPD caused by these 4 serotypes. Consequences of homelessness include overcrowded conditions within shelters that predispose for respiratory infections. Vaccine uptake is low in PEH [25, 26], which may have impacted the increase of these serotypes among PEH (all 4 covered by the 23-valent polysaccharide vaccine [PPSV23], 4 and 7F additionally in PCV13). PEH are also much more likely to use drugs, and certain substances, particularly opioids, have been associated with increased risk of IPD [27]. It is likely that homelessness, especially sporadic homelessness, is underreported in ABCs cases, and that its impact on the high transmissibility of these 4 serotypes is underestimated.

Our primary purpose is to provide ongoing characterization of ABCs IPD isolates. It is important to provide capsular serotype distributions and antibiotic resistance features, since a new 20-valent PCV (PCV20) targeting additional serotypes is in advanced development [28], and the emergence of new resistant strains requires continued vigilance. For example, continued expansion of the highly resistant serotype 3/ST271, 15BC/CC3852, and 11A/CC156 variants that we have recently detected is of concern, since these serotypes are not targeted (or ineffectively targeted in case of serotype 3) by PCV13. For these considerations, the year 2018 data were confirmatory of continuing small reductions of vaccine-type strains and emergence of nonvaccine strains [[10], [11]]. A notable exception was the continued localized expansion of apparent serotype-switch variant 4/ST10172 IPD among adults that was first recovered during 2013 from a PCV13-vaccinated infant [6]. The serotype 4/ST10172 variant potentially arose from a serotype 23A genetic recipient during the post-PCV13 period since ST10172 is closely similar to previously serotype 23A genotypes described during the pre-PCV era. Following 2013, serotype 4 IPD has been absent among young children; however, ABCs data from 2015–2018 revealed serotype 4 IPD clusters within states with the highest proportions of PEH, particularly within Colorado and California [4]. The vulnerability of PEH to serotype 4 IPD seems more associated with inherent properties of the serotype 4 capsule than with specific underlying clonal features, since 3 independent lineages (CC10172, CC244, CC695) each represented independent clusters. ST244 and ST695 are distantly related STs (positive for pilus-1 locus) that were commonly observed among pediatric serotype 4 isolates in the pre-PCV7 era [16]. Serotype 4/ST695 served as the recipient for a successful serotype 19A serotype switch that generated serotype 19A/ST695, first detected in the post-PCV7 era [29, 30]. The 27 serotype 19A/ST695 isolates recovered during 2018 (Supplementary Table 1) showed little clustering compared to serotype 4/ST695 isolates, were not associated with PEH, and were not recovered in California (data not shown).

The 4 serotypes with the highest incidence in PEH also displayed the highest proportions of clustering isolates—that is, groups of isolates that appeared nearly isogenic and with a very close temporal relationship. Serotypes 12F, 20, and 7F have shown disproportionate proportions of isolates from PEH during each of the years 2015–2018 in ABCs compared to non–serotype 4 serotypes, ranging from 11% to 33% each year (unpublished data). Only serotype 4 has shown an obvious continuing trend of isolate increase, with 34.3%–50% of serotype 4 isolates from PEH each year, and incrementally increased proportions of clustering isolates each year [4]. These 4 serotypes were uniformly comprised of basally penicillin-susceptible isolates, although resistance to other antibiotics was apparent. Lack of penicillin nonsusceptibility potentially correlates with decreased opportunity for recombination due to low carriage duration [31], which is also consistent with the apparent high transmissibility of these 4 serotypes. In a recent study, carriage duration appeared to contribute more to frequencies of individual resistance than horizontal gene transfer rates in different lineages, and was most apparent for the frequency of penicillin resistance [32].

The large surveillance population and broad geographic distribution of ABCs, combined with the advent of routine WGS, provide unique opportunities for strain surveillance. These features of ABCs readily allow detection and quantitation of rare events such as near isogenic strains shared between 2 different residents of the same LTCF. Without representation of ABCs in key western states, we would not have detected recent IPD clusters due to both PCV13 serotypes (4 and 7F) and non-PCV13 serotypes (12F and 20) that disproportionally affect PEH. Although there are no specific recommendations for pneumococcal vaccinations for PEH, such recommendations could potentially benefit this disadvantaged segment of our society.

Overall IPD rates within ABCs have fluctuated little during 2014–2018, with very low rates in young children, and limited signs of nonvaccine serotype “replacement disease” in older individuals [3]. Further opportunity exists to further reduce PCV13 serotypes 3, 4, 19A, and 19F, although the potential to reduce serotype 3 IPD through vaccination remains uncertain. PPSV23 and PCV13 are recommended alone or in series for select adults. The expanded experimental conjugate vaccine, PCV20, containing PCV13 and additional PPSV23 serotypes 8, 10A, 11A, 12F, 15B, 22F, and 33F [29], is predicted to confer more robust protection against serotypes shared with PPSV23, and would target a significant remaining IPD burden in the United States.