Welcome to the ISPPD 2022 Meeting Calendar

Background

The pneumococcal conjugate vaccines (PCVs) protect against diseases caused by Streptococcus pneumoniae, such as meningitis, bacteremia, and pneumonia. Estimating the population-level impact – including direct and indirect effects – of PCVs is challenging because of the lack of a perfect control population and the subtleness of signals when the outcome – like all-cause pneumonia – is attributable to a wide range of pathogens. Here we present a new approach to estimate PCVs’ impacts – using LASSO regression to predict the counterfactual outcome in different age groups for vaccine impact inference.

Methods

First, we designed a simulation study to test the performance of LASSO regression and three established methods – interrupted time series (ITS), synthetic control (SC), and seasonal-trend decomposition plus PCA (STL+PCA) – by comparing their ability to estimate the pre-specified vaccine impact. Then we applied LASSO to published pneumonia hospitalization data from Chile, Ecuador, Mexico, and the US.

Results

In the simulations, we found that both LASSO and SC achieved accurate and precise estimation, with high coverage (LASSO: 96–100%; SC: 69–89%); while estimates from ITS and STL+PCA were sometimes biased, with variable coverage (ITS: 0­–100%; STL+PCA: 0–100%). The performance of LASSO and SC remained robust in complex simulation scenarios where the association between outcome and all control variables was non-causal. When applied to real data, we found that LASSO yielded similar estimates of vaccine impact to SC.

Conclusions

The LASSO method is accurate, easily implementable and interpretable. In complement to existing methods like SC, LASSO can be used to study the population-level impact of PCVs and other vaccines.

Background

Interactions of Streptococcus pneumoniae with viruses feature in the pathogenesis of numerous respiratory illnesses.

Methods

We undertook a case-control study among adults at Kaiser Permanente Southern California between 2015-2019. Cases were individuals diagnosed with lower respiratory tract infection (LRTI; including pneumonia or non-pneumonia LRTI diagnoses) with viral infections detected by multiplex polymerase chain reaction testing. Eligible controls without LRTI diagnoses were matched to cases by demographic and clinical attributes. We measured vaccine effectiveness (VE) for PCV13 against virus-associated LRTI via the adjusted odds ratio of PCV13 receipt.

Results

Analyses included 15,298 virus-associated LRTI cases and 284,972 matched controls. Receipt of PCV13 was associated with 24.5% (95% confidence interval: 18.2-30.3%) VE against virus-associated pneumonia and 16.1% (5.7-25.4%) VE against other (non-pneumonia) virus-associated LRTI. We estimated 25.6% (18.8-31.9%) and 15.4% (6.5-23.4%) VE against all virus-associated LRTI episodes diagnosed in inpatient and outpatient settings, respectively. We identified statistically-significant protection against LRTI episodes associated with influenza A and B viruses, endemic human coronaviruses, parainfluenza viruses, human metapneumovirus, and enteroviruses, but not respiratory syncytial virus or adenovirus infections.

Conclusions

Among adults, PCV13 conferred moderate protection against virus-associated LRTI. Public health impacts of PCVs may be mediated, in part, by effects on polymicrobial interactions between pneumococci and respiratory viruses.

Background

Following the introduction of pediatric 13-valent pneumococcal conjugate vaccine (PCV13) programmes, the decline in serotype 3 (SPN3) has been less than for other vaccine serotypes and in some settings incidence has increased, coincident with a shift in the main circulating SPN3 clade, from I to II. The development of a novel SPN3 human challenge model will allow the interaction between PCV13 and SPN3 in the upper airway to be investigated.

Methods

A human challenge study involving three well characterized and antibiotic sensitive isolates of SPN3 (PFESP306 [clade Ia], PFESP231 [no clade] and PFESP505 [clade II]). Isolates were selected based on antibiotic sensitivity, phylogenesis, clade affiliation, presence of virulence/colonization genes, and pneumococcal chain length in liquid culture, the latter positively correlating with achieved average human experimental pneumococcal colonization rates. Doses were escalated (10,000cfu- 160,000 cfu) until maximal colonization rates with concurrent acceptable safety were achieved. Presence and density of experimental SPN3 nasopharyngeal colonization in nasal wash samples were assessed using microbiological and molecular methods, on days 2, 7 and 14 post-inoculation.

Results

96 healthy participants (median age 21, interquartile range 19-25) were inoculated, with all isolates efficiently and safely colonising the nasopharynx. Colonisation rates were 30.0-70.0% based on dose/isolate. 30% (29/96) reported mild symptoms (82.8% sore throat, [24/29]) with the majority at higher doses. There were no serious adverse events.

Conclusions

An SPN3 human challenge model is feasible and safe with comparable carriage rates to a SPN6B model. SPN3 carriage may cause mild upper respiratory symptoms.

Background

Persons experiencing homelessness (PEH) have high rates of invasive pneumococcal disease (IPD). Pneumococcal vaccines recently approved for use in U.S. adults provide an opportunity to reduce IPD among PEH.

Methods

We used statewide surveillance data, census estimates, and Point-in-Time counts to calculate age-adjusted IPD incidence among PEH aged ≥18 years in Anchorage, Alaska from 2005–2020. We compared IPD incidence among PEH and the general population in Anchorage, Alaska, and determined the proportion of cases that could be prevented by 20-valent pneumococcal conjugate vaccine (PCV20).

Results

During 2005–2020, 147 IPD cases were reported among PEH in Anchorage for an age-adjusted incidence rate of 910 cases per 100,000 person-years (95% CI: 745–1,075). IPD rates were 45-fold higher (95% CI: 37–55) among PEH compared to the general population. Among PEH, the average annual age-adjusted rate of IPD increased 3.8-fold from 505 per 100,000 (95% CI: 370–641) during 2005–2015 to 1,925 per 100,000 (95% CI: 1,458–2,392) during 2016–2020. Overall, among 147 PEH with IPD, 140 (95%) were aged ≥65 years (N=6) or aged 19–64 years with ≥1 high-risk condition (N=134), and 100 (68%) were infected with a PCV20 serotype, most commonly serotypes 12F (N=31), 4 (N=25), 8 (N=13), or 7F (N=10).

Conclusions

During 2005–2020, adult PEH in Anchorage experienced a higher burden of IPD compared to the general population and incidence increased significantly during 2016–2020. Most infections were caused by a PCV20 serotype and occurred among persons who would meet the recently approved vaccine recommendations.

Background

Major cardiovascular events, including acute myocardial infarction (AMI), have been reported among patients with invasive pneumococcal disease (IPD). Yet, whether IPD is causally associated with AMI remains unclear. We sought to determine if laboratory confirmed IPD was associated with the risk of AMI.

Methods

We conducted a self-controlled case series (SCCS) analysis among adult Tennessee residents with evidence of laboratory confirmed IPD as identified by the Tennessee Active Bacterial Core surveillance system (2003-2019). Patients entered the cohort 52 weeks prior to their IPD specimen collection date and were followed through the earliest of date of death, week 52 after IPD or end of study (12/2019). Risk periods included a pre-IPD (day -7 to day -1 before IPD date), an acute IPD (day 0 to 7 after IPD date), a post-acute IPD (day 8 to 28 after IPD date) and a control (all other follow-up time) risk period. We used conditional Poisson regression to perform within-person comparisons and to calculate age-adjusted incidence rate ratios for each risk period compared to control periods.

Results

Among 3,140 patients with laboratory confirmed IPD, 13.9% (n=438) had an AMI episode during follow-up. The incidence of AMI was significantly higher during both the pre-IPD (IRR: 8.3; 95% CI: 5.6-12.4) and the acute IPD (IRR: 47.7; 95% CI: 37.5-60.9) risk periods compared to control periods. No difference was observed for the post-acute IPD risk period.

Conclusions

The risk of AMI was substantially increased during laboratory confirmed IPD periods compared to control periods.

Background

Pneumococcal serotype 3 (SPN3) remains a common cause of adult and pediatric disease despite widespread use of SPN3 containing 13-valent pneumococcal conjugate vaccine (PCV13) in pediatric national immunization programs (NIPs) globally.

Methods

Data were collated from different disciplines to create a coherent explanation for serotype 3 epidemiology and vaccine response.

Results

Evidence supports PCV13 efficacy and effectiveness among directly vaccinated adults and children against SPN3 pneumonia, otitis media, and IPD. Data suggest some carriage impact as well: in countries using PCV13 in their pediatric NIPs, all-age SPN3 IPD usually declines for several years and then rises to levels approaching the pre-PCV13 era, while PCV10-using countries see a more rapid increase above baseline. Analyses of global and country-specific SPN3 strains demonstrate a switch from clade Ia, which previously dominated and which declined following PCV13 introduction, to clade II, which shows substantially greater macrolide/tetracycline resistance and altered sub-capsular proteins. Evidence to date does not support a role for PCV13 use in the emergence of clade II and no difference in capsules between clade Ia and clade II has been seen.

Conclusions

PCV13 showed substantial impact on SPN3 disease when clade Ia was the predominant strain. Mechanisms for the current rise of clade II remain under investigation, but if they are independent of the capsule it is possible that newer higher-valency PCVs will have similar impact against SPN3 at the population level as PCV13.

Background

Studies have examined trends in causative serotypes of adult pneumococcal disease in the context of childhood conjugate-vaccine usage. Despite decreasing conjugate-vaccine serotype circulation, predicted adult disease reduction has been smaller than expected, with incidence potentially increasing. However, there is little information on disease severity trends over time.

Methods

We recorded clinical characteristics and outcomes in a retrospective cohort analysis of hospitalised adults from 2006-2018 in Bristol, spanning the introduction of PCV13 into the UK vaccination programme in 2010. Pneumococcal infection was confirmed by blood culture and/or urinary antigen.

Results

2657 admissions with pneumococcal disease were identified. 93% admissions were pneumonia, 4% meningitis, 3% other infections. In 976 cases the causative serotype was identified. Progressive serotype shift to non-PCV13 serotypes occurred (54% isolates pre-PCV13 versus 72% post-PCV13) with loss of serotypes contained in the PCV13 vaccination.

Pneumococcal pneumonia incidence increased throughout the study (P<0.05). However, median admission CURB65-score decreased: 3 (IQR2-4) pre-PCV13 versus 2 (IQR1-3) post-PCV13 (P<0.01). The proportion of patients with complications decreased [58% pre-PCV13 to 47% post-PCV13]. ITU admissions increased throughout the study (P<0.01), but all-cause inpatient mortality decreased from 28% pre-PCV13 to 15% post-PCV13. However, all-cause 1-year mortality remained 26% (P>0.05). Patients >65 years had a 35% 1-year mortality, with both 30-day and 1-year survival improving in the PCV-13 era in patients >80 years (P<0.01).

Conclusions

Serotype shift with increased non-PCV13 serotype disease occurred. Conversely, disease severity decreased, potentially from serotype shift away from more invasive serotypes. Prospective evaluation of adult pneumonia/pneumococcal disease trends is warranted.