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Introduction (ID 49)
O031 - EMERGENCE OF A STREPTOCOCCUS PNEUMONIAE SEROTYPE 3 CAPSULE VARIANT AMONGST CARRIAGE ISOLATES IN THE 8 YEARS SINCE PCV13 INTRODUCTION IN BLANTYRE, MALAWI (ID 574)
Abstract
Background
Several studies worldwide showed limited PCV13 efficacy against carriage of serotype 3 Streptococcus pneumoniae. Serotype 3 lineages vary substantially geographically and show tendency to recombine. We hypothesised that the apparent serotype 3 vaccine escape, in the context of reduced carriage of other vaccine serotypes (VTs), could be due to the emergence of nasopharyngeal niche-adapted lineages.
Methods
The genome and CPS locus sequences of 556 serotype-3 isolates (from Africa, Asia, Europe and America) were analysed. ML-phylogeny, antimicrobial resistance (tetM, mefA, ermB, cat gene presence and pbpX allelic profiles) and MLST profiles were calculated. Colony morphology was observed in microaerophilic and anaerobic conditions, and opsonophagocytosis of representative isolates was assessed using conjugate vaccine induced sera.
Results
We identified a serotype-3 CPS locus variant in 82% of Blantyre isolates (2015-2019), characterized by an 8-gene cluster deletion and unchanged colony morphology. ST700 is the dominant genotype with these characteristics: it was identified in invasive disease, and we observed higher resistance to opsonophagocytosis than other serotype 3 strains commonly carried in Blantyre. ST700 strains are characterised by a higher MIC to penicillin, significant genome reduction, and unique virulence gene profiles, including pathogenicity islands carrying bacteriocin synthesis genes and ABC-transporters.
Conclusions
We highlight the emergence of an AMR serotype 3 variant, characterised by a shorter, yet functional, CPS locus, genome reduction and a unique genetic and phenotypic profile which may enhance colonisation and disease. We propose that these characteristics have the potential to confer competitive advantage to this lineage, which should be considered when designing the next generation of pneumococcal vaccines.
O028 - PNEUMONIA MORTALITY IN RURAL GAMBIA (ID 336)
Abstract
Background
Pneumonia is a common cause of mortality in low-income countries, although, individual-level, population-based data are sparse.
Methods
10 years of standardised surveillance for pneumonia in Basse Health & Demographic Surveillance System residents aged ≥2 months. We determined patient characteristics associated with in-patient mortality.
Results
We detected 22,713 clinical pneumonia cases, 12,735 admissions and 486 deaths. Case-fatality was greatest in the 2-5 month (4.4% [114/2588]), 36-59 month (5.2% [64/1225]) and ≥15 year (6.2% [19/308]) age groups.
Compared to those with weight-for-height (WfH) z-score ≥0 mortality increased 2.10 times (95% CI 1.61, 2.73) with each increasingly negative standard deviation of WfH z-score (table 1).
Table 1. Pneumonia case fatality by weight-for-height z-score
Weight-for-Height | Clinical pneumonia death |
≥0 | 34/3811 (0.89%) |
<0 to -1 | 55/5215 (1.05%) |
<-1 to -2 | 65/5819 (1.12%) |
<-2 to -3 | 86/3405 (2.53%) |
<-3 | 187/2429 (7.70%) |
The effect of WfH on mortality was not modified by stunting (RRMH=1.87 [95%CI 1.41, 2.49]). The effect of stunting on mortality was modified by WfH (RRMH=1.19 [95%CI 0.93, 1.53]) with a residual effect of stunting with WfH z-score <-3 (RR=2.89 [95%CI 1.54, 5.41]). Mortality in hospitalised children with O2Sat<89% was 15.9% (91/571), 13.4% (96/715) with O2Sat<90%, 11.5% (106/925) with O2Sat<91%, 9.7% (114/1156) with O2Sat<92%, 7.3% (126/1650) with O2Sat<93%, 10.0% (29/291) with pneumococcal bacteraemia/lung aspiration, 14.4% (65/453) with non-pneumococcal bacteraemia/lung aspiration, and 3.2% (60/1898) with WHO endpoint radiological consolidation.
Conclusions
Pneumonia mortality in rural Gambia varied by age. Particular attention should be given to severely wasted children, those with O2Sat<92%, and community-based interventions should also target moderate wasting.
O029 - ELUCIDATING THE SPATIOTEMPORAL DYNAMICS OF STREPTOCOCCUS PNEUMONIAE IN SOUTH AFRICA USING GENETIC AND HUMAN MOBILITY DATA (ID 132)
Abstract
Background
Streptococcus pneumoniae is a globally endemic, human obligate bacteria, and a leading cause of pneumonia and meningitis worldwide. Despite the enormous public health burden, the extent and mechanisms of pneumococcal spread across spatial scales remains largely unknown.
Methods
We analyze 5970 geolocated pneumococcal genome sequences from pneumococcal disease patients, collected from 2000-2014 in South Africa. We develop mechanistic phylogeographic models to reconstruct pathogen spread, incorporating the generation time distribution, human mobility data provided by Facebook, population size, and underlying heterogeneities in sampling.
Results
We found that sequence pairs from the same genotype and the same province had 4.7[3.4-7.4] times the probability of having a MRCA within 3 years compared to sequence pairs from >1000km apart. Pneumococci become homogenously mixed across South Africa after 50 years (relative-risk=1). We were able to accurately recover this observed pattern of spatial-spread using our mechanistic model estimating that most transmission events were local (77% within municipality), with occasional long-distance transmissions. Our framework also showed the key role of travel to large cities in disease spread. We found that following an introduction, pneumococcus was 20 times more likely to have travelled to a major population hub (population >3-million) than elsewhere after one year of sequential person-to-person transmission.
Conclusions
Pneumococcus spreads slowly across South Africa, driven by limited long-distance human mobility and the long generation time of pneumococcus. Our framework provides an opportunity to explore whether similar patterns of spread are observed elsewhere with differing mobility patterns, or whether vaccine introduction results in different patterns of spread across pneumococcal serotypes.
O030 - MORTALITY AND SEQUELAE FOLLOWING PNEUMOCOCCAL MENINGITIS IN SOUTH AFRICA (ID 195)
Abstract
Background
Pneumococcal meningitis has high mortality and causes long-term sequelae in survivors. In an era of high HIV prevalence and post pneumococcal-conjugate-vaccine introduction we document the sequelae following pneumococcal meningitis.
Methods
From 2016-2020, we conducted sentinel surveillance at 25 hospitals across South Africa for episodes of laboratory-confirmed, physician-diagnosed pneumococcal meningitis. Data on mortality and sequelae at discharge amongst survivors were collected.
Results
Among 1319 cases of pneumococcal meningitis, 1199 (91%) had outcome data. The in-hospital case-fatality ratio was 41% (26%, 64/246 <5 years and 44%, 423/953 >5 years). On multivariable analysis, death was significantly associated with HIV-infection (adjusted odds ratio (aOR) 2.4, 95% confidence interval (CI) 1.6-3.5), admission Glasgow-Coma-Scale (GCS) of <15 (aOR 6.4, 95%CI 4.5-9.1) and underlying illness (aOR 2.8, 95%CI 1.9-4.0).
Among survivors with sequelae data, 25% (179/712) suffered sequelae, 7% (51/712) had >1 sequelae. The top three sequelae included: new-onset seizures (81, 11%), neurological fallout (70, 10%) and hearing loss (42, 6%). GCS <15 on admission (aOR 2.6, 95%CI 1.5-4.3) and having a pneumococcus resistant to first-line antibiotics (aOR 2.1, 95%CI 1.2-3.6) were predictive of sequelae.
Conclusions
Death and sequelae following pneumococcal meningitis remains high. HIV and underlying illness were associated with death, whereas GCS<15 was predictive of increased risk of death or sequelae.
O032 - INVASIVE PNEUMOCOCCAL DISEASE (IPD) MORTALITY RATES AND RISK FACTORS ASSOCIATED WITH 30-DAY MORTALITY IN ENGLAND; A PROSPECTIVE COHORT STUDY, 2000-2019 (ID 733)
Abstract
Background
Invasive pneumococcal disease (IPD) is a large burden on global morbidity and mortality, disproportionately affecting young children, the elderly and immunocompromised.
Methods
We used national IPD surveillance data from the UK Health Security Agency to study pre- to post- PCV vaccination trends in mortality in England (2000-2019) and used enhanced surveillance data (2014-2019) to identify clinical and epidemiological risk factors for 30-day case-fatality using logistic regression.
Results
There were 94,579 IPD cases between July 2000 and June 2019. Over 80-year-olds had the highest mortality rate which decreased by 61% from 104.4 deaths per 100,000 in 2000/01 to a nadir of 40.9 deaths per 100,000 in 2013/14, before increasing to 69.1 deaths per 100,000 in 2017/18. Additionally, mortality rate in <2-year-olds reduced by 67% from an average of 41.6 deaths per 100,000 in the pre-PCV7 period to 13.6 deaths per 100,000 in 2018/19.
During 2014-2019 (n=22,160), after adjusting for age-group, epidemiological year and serotype group, chronic diseases of the liver (adjusted Odds Ratio (aOR): 2.86, 95%CI (2.47-3.32)), kidneys (aOR: 1.22, (1.11-1.35)) and heart (aOR: 1.19, (1.10-1.30)), sickle-cell disease (aOR: 2.52 (1.27-5.00)), cerebrospinal fluid leaks (aOR: 1.36, (1.10-1.68)) and malignancy/immunosuppression (aOR: 1.14, (1.04-1.24)) were associated with increased 30-day case-fatality rate. PCV7, additional PCV13 and non-vaccine serotypes were associated with increased risk (aOR range: 1.34-1.60) compared to additional PPV23 serotypes.
Conclusions
Mortality rates in young children and older adults showed the greatest decline following pneumococcal conjugate vaccine introduction. Several comorbidities were independently associated with increased risk of death, notably, chronic liver disease.
O033 - INCIDENCE OF PNEUMOCOCCAL PNEUMONIA HOSPITALIZATIONS BEFORE AND DURING THE COVID-19 PANDEMIC IN TENNESSEE AND GEORGIA: RESULTS FROM THE PNEUMO STUDY (ID 316)
Abstract
Background
Understanding the burden of pneumococcal pneumonia is essential for assessing potential impact of vaccines. The COVID-19 pandemic caused major changes in the epidemiology of acute respiratory infections. We calculated incidence of all-cause and pneumococcal pneumonia hospitalizations among US adults before and during the COVID-19 pandemic.
Methods
As part of the ongoing Pneumococcal Pneumonia Epidemiology, Urine Serotyping, and Mental Outcomes (PNEUMO) study, we prospectively enrolled adults hospitalized with clinical and radiographic evidence of pneumonia. At 1 hospital in Nashville we enrolled all pneumonia patients (including COVID-19) for 3 years (2018-2019, 2019-2020, 2020-2021) and at 2 hospitals in Atlanta we enrolled pneumonia patients without COVID-19 for 1 year (2018-2019). Pneumococcal etiology was determined by BinaxNOW urine antigen tests, respiratory cultures, and sterile site cultures (which identified invasive pneumococcal pneumonia). Incidence of hospitalizations for all-cause and pneumococcal pneumonia was calculated using market share methodology. During 2020-2021, we also collected information on COVID-19, including results of clinical SARS-CoV-2 tests.
Results
Of 2,558 enrolled patients with all-cause pneumonia, 164 (6.4%) had pneumococcal pneumonia, including 101 (3.9%) with non-invasive pneumococcal pneumonia, and 63 (2.5%) with invasive pneumococcal pneumonia. Of 191 patients with COVID-19 enrolled during the 2020-2021 year, 3 (1.6%) had co-detection of S. pneumoniae. Compared to the year prior to the COVID-19 pandemic, incidence of all-cause pneumonia was maintained during the pandemic years while the incidence of pneumococcal pneumonia decreased (Table).
Conclusions
During the COVID-19 pandemic in the US, hospitalizations for pneumococcal pneumonia declined. Co-infection with SARS-CoV-2 and pneumococcus was rare.
O034 - A SYSTEMATIC REVIEW OF TRENDS IN PNEUMONIA AND PNEUMONIA-RELATED MORTALITY INCIDENCE AMONG CHILDREN LESS THAN 10 YEARS OF AGE IN LOW AND MIDDLE INCOME COUNTRIES (ID 86)
Abstract
Background
Pneumonia is the leading infectious cause of child mortality and 95% of pneumonia-related deaths occur in low- and middle-income countries (LMICs). SDG3 calls for a reduction in child mortality. We conducted a systematic review to assess trends in pneumonia incidence and pneumonia mortality incidence using empiric data and compared this with modelled estimates from the Institute for Health Metrics and Evaluation (IHME) to assess progress towards achieving SDG3.
Methods
Systematic search of Ovid Medline, Embase, and Pubmed using keywords and Mesh terms. Observational studies conducted in LMICs of pneumonia or pneumonia mortality incidence in children aged <10years with at least two estimates over at least five years were included. Modelled estimates were extracted from the 2020 IHME database.
Results
Of 4084 records, 280 underwent full-text screening and 30 were included. Three countries were classified as low-income. Pneumonia incidence was reported in 17 studies across 12 countries, with declines observed in all but one country. Pneumonia mortality incidence was reported in 15 studies from 18 countries, with declines in 16/18 countries. Four studies in China estimated mortality incidence across subpopulations, reporting higher starting incidence and greater declines in minority and rural populations. Most empiric trends and IHME-modelled estimates reported declining incidence, however the magnitude of declines varied.
Conclusions
Most studies reported declines in pneumonia and pneumonia mortality incidence, but trends did not always align with modelled estimates. Reliance on national trends may miss important differences in subpopulations. Consistent definitions of pneumonia, data sources, and methodology are required to compare country progress towards SDG3 targets.
O035 - PROGRESS IN PNEUMONIA CONTROL FOR CHILDREN IN LOW-AND-MIDDLE INCOME COUNTRIES: A SYSTEMATIC REVIEW OF COUNTRIES REPORTING ON PNEUMONIA INDICATORS (ID 190)
Abstract
Background
Background
The goal of the integrated Global Action Plan for Prevention and Control of Pneumonia and Diarrhoea (GAPPD) is to end preventable childhood deaths by 2025 with targets and indicators to monitor progress. The aim of this systematic review is to summarise how low-and-middle income countries (LMICs) reported pneumonia-specific GAPPD indicators and whether GAPPD targets have been achieved.
Methods
Methods
A systematic literature search was performed in August 2020. Publications/reports between 2015 and 2020 reporting on two or more GAPPD-pneumonia indicators from LMICs were included. Data prior to 2015 were included if available in the same report series. A narrative synthesis of the literature was performed.
Results
Results
17 publications/reports met inclusion criteria with data available from 139 LMICs. Most GAPPD indicators were reported at the national level with minimal reporting at the subnational level. Immunisation coverage (Haemophilus influenzae, measles, diphtheria-tetanus-pertussis vaccines) in the WHO Europe, Americas and South-East Asia regions were meeting 90% coverage targets, while pneumococcal conjugate vaccine coverage was lagging globally. The remaining GAPPD indicators (breastfeeding, pneumonia case management, antiretroviral prophylaxis, household air pollution) were not meeting GAPPD targets. There was a strong negative correlation between GAPPD coverage rates and under-five mortality.
Conclusions
Conclusions
There is substantial progress to be made in LMICs to achieve the 2025 GAPPD targets. Current GAPPD indicators should be reviewed with consideration of adding undernutrition and access to oxygen therapy as important indicators which impact pneumonia outcomes. Further research on GAPPD indicators at subnational levels can help identify high-risk populations for targeted pneumonia interventions.