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Introduction (ID 60)
O079 - ADULTS LIVING WITH HIV ON ANTIRETROVIRAL THERAPY EXHIBIT PROLONGED HIGH-DENSITY PNEUMOCOCCAL CARRIAGE AND SHED ANTIMICROBIAL-RESISTANT PNEUMOCOCCI (ID 100)
Abstract
Background
Despite the successful rollout of the pneumococcal conjugate vaccines, vaccine serotype (VT) carriage remains high among People Living with HIV (PLHIV) on antiretroviral therapy (ART). We investigated the impact of HIV infection on pneumococcal carriage duration, density, shedding, and antimicrobial resistance (AMR).
Methods
In a prospective cohort study, we recruited 90 asymptomatic PLHIV on ART and 54 HIV-uninfected adults aged 18-45 years and followed them up at regular intervals for 12 months. Standard microbiological techniques were used to test for pneumococcal presence and density on the nasopharyngeal swab and shedding specimens (cough, nose poke, and facemask). Disk diffusion using oxacillin, tetracycline, erythromycin, and co-trimoxazole was performed to screen AMR.
Results
PLHIV on ART had a longer duration of pneumococcal carriage (133 [95% CI 112-140] vs. 49 [95% CI 26-66] days; p=0.0012) and higher pneumococcal carriage density (51088 [95% CI 27542-95499] vs. 7630 [95% CI 3467-16218] CFU/ml; p=0.0394) than HIV-uninfected adults. PLHIV on ART were more likely to shed pneumococcus than HIV-uninfected adults (46% vs 25%; p=0.002). Shed isolates were more often multidrug-resistant (MDR) than the nasopharyngeal carriage isolates (57% vs. 36%; p=0.0015). A generalized linear mixed model demonstrated that being HIV-infected on ART (p=0.017) or having a higher carriage density (p=0.0002) were independently associated with increased pneumococcal shedding.
Conclusions
We have demonstrated profoundly greater risks of pneumococcal carriage and shedding among PLHIV on ART compared to HIV-uninfected adults. These findings suggest that PLHIV on ART could be an important reservoir of pneumococcal transmission, including AMR pneumococci.
O080 - ASSOCIATION OF THE 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IMPLEMENTATION WITH THE INCIDENCE OF ACUTE CHEST SYNDROME IN CHILDREN: A TIME-SERIES ANALYSIS FROM A 13-YEAR NATIONAL SURVEILLANCE (ID 205)
Abstract
Background
Acute chest syndrome (ACS) is a major complication of sickle-cell disease (SCD). Although Streptococcus pneumoniae is highly prevalent in children with SCD, its precise role in ACS is unclear. The impact of 13-valent pneumococcal conjugate vaccine (PCV13) implementation on ACS remains unknown. We aimed to assess the association of PCV13 implementation in the general pediatric population with the incidence of ACS in children with SCD.
Methods
We conducted an interrupted time-series analysis using an exhaustive national surveillance system. All children aged <18 years with SCD hospitalized for ACS, based on the ICD-10, between 2007 and 2019 were included. The monthly incidence of ACS per 1,000 children with SCD was analyzed by segmented linear regression with autoregressive error. We analyzed the monthly incidence of hospitalization for vaso-occlusive crisis, asthma crisis, and acute pyelonephritis per 1,000 children with SCD over the same period as control outcomes.
Results
Among the 107,694 hospitalizations of children with SCD, we included 4,007 episodes of ACS. PCV13 implementation in 2010 was associated with a significant decrease in the incidence of ACS (-0.9% per month, p=0.0007), with an estimated cumulative effect of -41.8% (95% CI [-70.8;-12.7]) by 2019. By contrast, no change was found for the three control outcomes over the study period.
Conclusions
PCV13 implementation was associated with an important reduction in the incidence of ACS in children with SCD. This vaccine benefit provides new evidence of the key role of Streptococcus pneumoniae in ACS and should be considered when estimating the impact of current and next-generation PCVs in children.
O081 - EVOLVING RISK PROFILE OF PATIENTS WITH INVASIVE PNEUMOCOCCAL DISEASE DURING THE PNEUMOCOCCAL CONJUGATE VACCINE ERA (ID 276)
Abstract
Background
The incidence of invasive pneumococcal disease (IPD) due to serotypes covered by pneumococcal conjugate vaccines (PCVs) has declined since PCVs introductions. Whether the risk profile of IPD cases has changed following PCVs introductions is unclear.
Methods
We examined the comorbidity profile of all laboratory-confirmed IPD cases identified in Tennessee through active population and laboratory-based surveillance (1999-2018). Comorbidities were identified through chart review and classified as high-risk and at-risk (Figure footnote). We examined changes in the proportion of patients with relevant comorbidities over time, and stratified estimates according to serotype information.
Results
The overall number of IPD declined modestly over the study period. By 2017-2018, IPD due to PCV7 serotypes was very rare; IPD due to the 6 additional serotypes included in PCV13 declined below 1999-2000 levels after more than a doubling early in the decade; and IPD due to non-PCV13 serotypes steadily increased reaching ~80% of the total IPD cases. The proportion of all IPD cases with high-risk and at-risk comorbidities increased over time from 11% (1999-2000) to 27% (2017-2018) and from 25% to 60%, respectively (Figure).
Conclusions
After widespread use of PCVs, patients with residual IPD in Tennessee have a higher prevalence of relevant comorbidities than in previous years. These risk profile changes need to be considered in future prevention plans.
O082 - IMPACT OF PCV ON DRAINING OTITIS MEDIA AMONG NATIVE AMERICAN CHILDREN UNDER 5 YEARS OF AGE LIVING ON NAVAJO AND WHITE MOUNTAIN APACHE TRIBAL LANDS (ID 456)
Abstract
Background
Native American children living on the Navajo and White Mountain Apache (WMA) tribal lands experience a high burden of otitis media (OM). We assessed the impact of pneumococcal conjugate vaccines (PCV7 introduced in 2000; PCV13 in 2010) on draining OM.
Methods
Through laboratory-based surveillance we identified pneumococci grown from OM specimens from Navajo and WMA children under 5 years of age. Pneumococci were serotyped. Culturing middle ear fluid was done at the provider’s discretion and practices varied over time, so yearly change in the odds of vaccine-type pneumococcal OM was assessed separately for PCV7-type (2000-2009) and PCV13-type (2010-2019) using a generalized linear model with a logit link and overdispersion parameter. PCV7-types were 4, 6B, 9V, 14, 18C, 19F, and 23F. PCV13-types were 1, 3, 5, 6A, 7F, 19A and PCV7-types.
Results
308 cases of pneumococcal OM were identified from 2000-2019 (Figure); serotypes were available from 236 (77%). The odds of vaccine-type OM declined yearly during the PCV7 period (OR=0.56, 95% CI: 0.29-0.81); however, a similar trend was not observed during the PCV13 period (OR=0.99, 95% CI: 0.86–1.15). During 2010-2019, serotypes 3, 19A, and 19F accounted for 96% of PCV13-type cases and 42% of all cases. Eighty percent of children with PCV13-type OM were fully vaccinated for age.
Conclusions
Use of PCV7 in this population was associated with a decline in the proportion of OM caused by PCV7-type; however, vaccine-type OM (predominantly 3, 19A, and 19F) persisted in the PCV13 era. Most vaccine-type cases occurred in PCV-vaccinated children.
O083 - IMPACT OF PNEUMOCOCCAL CONJUGATE VACCINES (PCV) ON INVASIVE PNEUMOCOCCAL DISEASE (IPD) AMONG ALASKA NATIVE/AMERICAN INDIAN (AN/AI) CHILDREN AGED (ID 464)
Abstract
Background
PCV have significantly reduced high rates of IPD among AN/AI children. We compared IPD rates among AN/AI and non-Native children in Alaska during the decade before use of 7-valent PCV (1991‒2000), after use of PCV7 but before 13-valent PCV (2001‒2010), and after PCV13 (2011‒2020).
Methods
We used Alaska IPD surveillance data for 1991–2020 to calculate rates per 100,000 among children aged <5 years and used 95% confidence intervals (CI) and incidence rate ratios (IRR) to compare rates by race.
Results
Average annual IPD rates among AN/AI children in Alaska decreased by 80% overall, from 250 per 100,000 (95% CI: 224‒278) during 1991‒2000, to 109 (95% CI: 93‒128) during 2001‒2010, and 49 (95% CI: 39‒61) during 2011‒2020. During these same time-periods, IPD rates decreased by 88% among non-Native children from 68 per 100,000 (95% CI: 61‒76) pre-PCV7, to 27 (95% CI: 22‒33) post-PCV7, and 8 (95% CI: 6‒11) post-PCV13. IPD rates remained higher among AN/AI children compared to non-Native children during all three time-periods, with an IRR of 3.7 (95% CI: 3.1‒4.3) during 1991‒2000, 4.0 (95% CI: 3.1‒5.2) during 2001‒2010, and 6.1 (95% CI: 4.0‒9.3) during 2011‒2020. From 1991‒2000 to 2011‒2020, PCV13-type IPD decreased by 95% (206 to 9 per 100,000 children) among AN/AI and 97% among non-Native children (56 to 2 per 100,000 children).
Conclusions
Overall and PCV13-type IPD rates decreased significantly from pre-PCV7 to post-PCV13 time-periods among both AN/AI and non-Native children in Alaska. However, disparities in IPD rates remain that may be addressed by new PCV.
O084 - IMPACT OF PNEUMOCOCCAL CONJUGATE VACCINES (PCV) AND THE COVID-19 PANDEMIC ON INVASIVE PNEUMOCOCCAL DISEASE (IPD) AMONG NATIVE AMERICANS LIVING ON THE NAVAJO NATION (ID 116)
Abstract
Background
Native Americans living on reservations experience high rates of IPD. A 7-valent PCV was introduced in 2000 for children <5 years. In 2010, a 13-valent PCV replaced PCV7 in the US. In late 2014, PCV13 was recommended for adults ≥65 years; this recommendation was revised in 2019, to recommend shared clinical decision-making. COVID-19 and associated mitigation strategies affected the spread of other respiratory diseases.
Methods
We conducted active, laboratory-based surveillance for IPD in Native Americans living on or around the Navajo Nation from 1995-2021. Isolates were serotyped by Quellung reaction. We compared incidence before and after PCV13 introduction and emergence of COVID-19 using incidence rate ratios and binomial exact confidence intervals.
Results
Comparing the PCV7 and PCV13-eras, PCV13-type IPD incidence decreased 93% in children and 48% in adults (Table). Among adults ≥65 years, PCV13-type IPD incidence was unchanged after the adult recommendation (22.7/100,000 in 2011-2014 vs 29.3/100,000 in 2015-2019). Serotypes 3, 8, 12F, and 20 were the leading causes of IPD in the PCV13-era. Comparing the pre-PCV and PCV13-eras, overall incidence declined 85% in children and 25% in adults (Table). In 2020-2021 (COVID-19 era), overall incidence declined 91% in children and 44% in adults, compared to the PCV13-era (Table).
Conclusions
Use of PCVs resulted in a significant and sustained reduction in IPD on the Navajo Nation; however, the remaining burden is substantially higher than in the general U.S. Higher valency vaccines and risk reduction strategies could help address this disparity. The COVID-19 pandemic was associated with an unprecedented and dramatic decline in IPD.
O085 - CLINICAL AND MICROBIOLOGICAL PROFILE OF IPD IN HOSPITALIZED PATIENTS IN A TERTIARY BRAZILIAN HOSPITAL, 2000-2021 (ID 507)
Abstract
Background
A pneumococcal conjugate vaccine was introduced in Brazilian National Vaccination Program in 2010. This ongoing prospective study evaluates the effect of PCV10 use on the clinical and microbiological characteristics of IPD in all ages over the last 21 years in a single tertiary hospital in Sao Paulo, Brazil.
Methods
In our ongoing hospital-based surveillance study, all culture-positive IPD cases groups were evaluated from January 1, 2000, through December 31, 2021, in all ages. Serotypes, clinical characteristics, and outcomes were analyzed according to the pre-vaccination period (2000-2009) and post-vaccination period (2010-2021)
Results
701 isolates were recovered, of which 81.6% were serotyped. Nearly 71% of the pre-vaccination strains were PCV10 serotypes and declined to 38.8% in the post-vaccine era. Conversely, serotypes 3, 6A e 19A altogether increased from 7.6% to 15.5%; unique PPSV23 serotypes increased from 12.7% to 23.3% and non-vaccine serotypes (NVT) increased from 9% to 21.3%. Smoking (22.5%), alcohol and substance misuse (20.7%), cardiovascular diseases (18%), neoplastic diseases (13.5%), chronic respiratory disease (10.2%), HIV (9%), and homelessness (8.7%) are the leading risk factors in the post-vaccine period – driven largely by adults. Approximately 43% required intensive care; Overall, CFR was 24.5%, increased with age, and peaked among those with comorbidities (range: 19-47%).
Conclusions
Contrasting with the pre-vaccine era, IPD has turned into a disease affecting adults with comorbidities. The relative significance of non-PCV10 serotypes has almost doubled in the post-PCV10 period. ICU need and CFR remained high and varied widely across age groups, increased-risk conditions, and period studied.
O086 - INVESTIGATING MATERNAL TRANSFER OF PNEUMOCOCCAL AND NTHI PROTEIN ANTIBODIES IN AUSTRALIAN ABORIGINAL INFANTS (ID 337)
Abstract
Background
Australian Aboriginal and Torres Strait Islander, and Papua New Guinean (PNG) children, experience disproportionately high rates of pneumococcal and nontypeable Haemophilus influenzae (NTHi) infections. We demonstrated differences in pneumococcal and NTHi antibody ontogeny in PNG infants suggesting lower NTHi specific maternal antibody transfer. In this study we assessed if 1) antibody ontogeny was similar in Aboriginal infants and 2) if patterns were due to low maternal antibody titres or lack of placental transfer.
Methods
Antibody titres to pneumococcal (PspA1, PspA2, CbpA, Ply) and NTHi antigens (Protein D (PD), ChimV4, OMP26, rsPilA) were measured in 84 maternal, 80 cord and 27 7-month-old Aboriginal infant sera (IgG), and 145 breast milk samples collected at 1,2, 7 months (IgA) using in-house multi-plexed bead-based immunoassays.
Results
Antibody titres in cord and maternal sera were similar for all antigens, except Ply (higher in cord;p=0.004). Infant sera IgG were lower than cord blood titres for all pneumococcal antigens(p<0.001). Infant sera titres were higher compared to cord IgG for PD(p=0.029), similar for OMP26(p=0.817) and rsPilA(p=0.290) and lower for ChimV4(p=0.004). Breast milk IgA were similar at 1, 2 and 7 months for all antigens except OMP26 (lower at 7 months than 1 month(p=0.035)).
Conclusions
These data support previous findings demonstrating waning of maternally-derived pneumococcal, but not NTHi antibodies (except ChimV4) in young Aboriginal infants. The similarities between maternal and cord IgG, and the absence of waning, support a lack of maternal NTHi antibodies for cross-placental transfer. Maternal immunisation strategies should be considered for NTHi protein vaccines.