scholarly journals Elevated risk of invasive group A streptococcal disease and host genetic variation in the human leukocyte antigen locus

2019 ◽  
Author(s):  
Tom Parks ◽  
Katherine Elliott ◽  
Theresa Lamagni ◽  
Kathryn Auckland ◽  
Alexander J. Mentzer ◽  
...  
Keyword(s):  
Case Fatality ◽  
Human Leukocyte ◽  
Hla Typing ◽  
Bacterial Disease ◽  
Invasive Group ◽  
Increased Risk ◽  
Group A ◽  
Host Genetic ◽  
Hla Dqa1 ◽  
Human Leukocyte Antigen Locus

AbstractInvasive group A streptococcal (GAS) disease is uncommon but carries a high case-fatality rate relative to other infectious diseases. Given the ubiquity of mild GAS infections, it remains unclear why healthy individuals will occasionally develop life-threatening infections, raising the possibility of host genetic predisposition. Here, we present the results of a case-control study including 43 invasive GAS cases and 1,540 controls. Using HLA imputation and linear mixed-models, we find each copy of theHLA-DQA1*01:03 allele associates with a two-fold increased risk of disease (odds ratio 2.3, 95% confidence interval 1.3-4.4,P=0.009), an association which persists with classical HLA typing of a subset of cases and analysis with an alternative large control dataset with validated HLA data. Moreover, we propose the association is driven by the allele itself rather than the background haplotype. Overall this finding provides impetus for further investigation of the immunogenetic basis of this devastating bacterial disease.

scholarly journals Epidemiology of Invasive Group A Streptococcal Disease in Alaska, 2001 to 2013

2015 ◽  
Vol 54 (1) ◽  
pp. 134-141 ◽  
Author(s):  
Karen Rudolph ◽  
Michael G. Bruce ◽  
Dana Bruden ◽  
Tammy Zulz ◽  
Alisa Reasonover ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Case Fatality ◽  
Invasive Disease ◽  
Population Based ◽  
The Arctic ◽  
Surveillance Program ◽  
Bacterial Disease ◽  
Invasive Group ◽  
Laboratory Surveillance ◽  
Group A

The Arctic Investigations Program (AIP) began surveillance for invasive group A streptococcal (GAS) infections in Alaska in 2000 as part of the invasive bacterial diseases population-based laboratory surveillance program. Between 2001 and 2013, there were 516 cases of GAS infection reported, for an overall annual incidence of 5.8 cases per 100,000 persons with 56 deaths (case fatality rate, 10.7%). Of the 516 confirmed cases of invasive GAS infection, 422 (82%) had isolates available for laboratory analysis. All isolates were susceptible to penicillin, cefotaxime, and levofloxacin. Resistance to tetracycline, erythromycin, and clindamycin was seen in 11% (n= 8), 5.8% (n= 20), and 1.2% (n= 4) of the isolates, respectively. A total of 51emmtypes were identified, of whichemm1 (11.1%) was the most prevalent, followed byemm82 (8.8%),emm49 (7.8%),emm12 andemm3 (6.6% each),emm89 (6.2%),emm108 (5.5%),emm28 (4.7%),emm92 (4%), andemm41 (3.8%). The five most commonemmtypes accounted for 41% of isolates. Theemmtypes in the proposed 26-valent and 30-valent vaccines accounted for 56% and 78% of all cases, respectively. GAS remains an important cause of invasive bacterial disease in Alaska. Continued surveillance of GAS infections will help improve understanding of the epidemiology of invasive disease, with an impact on disease control, notification of outbreaks, and vaccine development.

scholarly journals Household transmission of invasive group A Streptococcus infections in England: a population-based study, 2009, 2011 to 2013

2017 ◽  
Vol 22 (19) ◽  
Author(s):  
Rachel Mearkle ◽  
Maria Saavedra-Campos ◽  
Theresa Lamagni ◽  
Martine Usdin ◽  
Juliana Coelho ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Case Fatality ◽  
Secondary Case ◽  
Time Interval ◽  
Number Needed To Treat ◽  
Short Time Interval ◽  
Primary Case ◽  
Invasive Group ◽  
Increased Risk ◽  
Group A

Invasive group A streptococcal infection has a 15% case fatality rate and a risk of secondary transmission. This retrospective study used two national data sources from England; enhanced surveillance (2009) and a case management system (2011–2013) to identify clusters of severe group A streptococcal disease. Twenty-four household pairs were identified. The median onset interval between cases was 2 days (range 0–28) with simultaneous onset in eight pairs. The attack rate during the 30 days after first exposure to a primary case was 4,520 per 100,000 person-years at risk (95% confidence interval (CI): 2,900–6,730) a 1,940 (95% CI: 1,240–2,880) fold elevation over the background incidence. The theoretical number needed to treat to prevent one secondary case using antibiotic prophylaxis was 271 overall (95% CI: 194–454), 50 for mother-neonate pairs (95% CI: 27–393) and 82 for couples aged 75 years and over (95% CI: 46–417). While a dramatically increased risk of infection was noted in all household contacts, increased risk was greatest for mother-neonate pairs and couples aged 75 and over, suggesting targeted prophylaxis could be considered. Offering prophylaxis is challenging due to the short time interval between cases emphasising the importance of immediate notification and assessment of contacts.

scholarly journals Host genetic variants near the PAX5 gene locus associate with susceptibility to invasive group A streptococcal disease

2019 ◽  
Author(s):  
Tom Parks ◽  
Kathryn Auckland ◽  
Theresa L. Lamagni ◽  
Alexander Mentzer ◽  
Katherine Elliott ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Clinical Manifestations ◽  
Invasive Group ◽  
Genome Wide ◽  
A Genome ◽  
Increased Risk ◽  
Combining Data ◽  
Group A ◽  
Risk Of Disease ◽  
Host Genetic

AbstractWe undertook a genome-wide association study of susceptibility to invasive group A streptococcal (GAS) disease combining data from distinct clinical manifestations and ancestral populations. Amongst other signals, we identified a susceptibility locus located 18kb from PAX5, an essential B-cell gene, which conferred a nearly two-fold increased risk of disease (rs1176842, odds ratio 1.8, 95% confidence intervals 1.5-2.3, P=3.2×10−7). While further studies are needed, this locus could plausibly explain some inter-individual differences in antibody-mediated immunity to GAS, perhaps providing insight into the effects of intravenous immunoglobulin in streptococcal toxic shock.

scholarly journals 1891. Invasive Group A Streptococcus Infections Among Residents of Multiple Nursing Homes—Denver, Colorado, 2017–2018

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S55-S56
Author(s):  
Osatohamwen Idubor ◽  
Nisha B Alden ◽  
Srinivas Nanduri ◽  
Abimbola Ogundimu ◽  
Sukarma S S Tanwar ◽  
...  
Keyword(s):  
Nursing Homes ◽  
Infection Control ◽  
Group A Streptococcus ◽  
Multiple Infection ◽  
Invasive Group ◽  
Increased Risk ◽  
Group A ◽  
Sterile Site ◽  
Colorado Department ◽  
Emm Type

Abstract Background Older adults residing in nursing homes (NH) are at increased risk for invasive group A Streptococcus (GAS) infections due to advanced age, presence of wounds, and comorbidities; approximately one-third of infected patients die. Beginning in 2015, increasing numbers of GAS infections in NH residents and several NH clusters were reported from the Denver metropolitan area. Colorado Department of Public Health and Environment (CDPHE) and CDC investigated to characterize cases and assess if outbreaks resulted from interfacility transmission. Methods We reviewed data from Active Bacterial Core surveillance (ABCs) in the 5-county Denver area from January 2017 to June 2018. We defined a case as isolation of GAS from a normally sterile site in an NH resident. GAS isolates underwent whole-genome sequencing (WGS) at CDC’s Streptococcus Laboratory to determine emm types for genotyping. Among isolates with the same emm type, pairwise single-nucleotide polymorphism (SNP) distances were calculated using Nucmer software. In October 2018, a CDPHE-CDC team assessed infection control at NHs with cases of the most common emm type. Results Over 18 months, among >100 NHs in the Denver area, ≥1 GAS case was identified in 29 NHs, with 6 having ≥3 cases. During this period, 68 cases in NH residents were identified. WGS identified 17 emm types among isolates from these cases; most common was emm11.10 (34%, n = 22), a rare subtype in ABCs. All emm11.10 isolates had nearly identical genomes (average pairwise SNP distance: 3.2), and were isolated from 10 NHs, with 2 NHs having ≥ 4 cases. Multiple infection control lapses were noted during site visits to 8 NHs. Conclusion Multiple outbreaks due to GAS were noted in 5-county Denver area NHs in 2017–2018. WGS of surveillance isolates identified a rarely seen emm subtype 11.10 from multiple facilities with temporal and genomic clustering suggesting interfacility GAS transmission. Disclosures All Authors: No reported Disclosures.

scholarly journals LB9. Rising High Rate of Invasive Group A Streptococcus Infections Among Persons Experiencing Homelessness in San Francisco, 2010–2017

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S762-S762
Author(s):  
Tara Scheuer ◽  
Tanya Libby ◽  
Chris Van Beneden ◽  
James Watt ◽  
Arthur Reingold ◽  
...  
Keyword(s):  
United States ◽  
San Francisco ◽  
Group A Streptococcus ◽  
Disease Incidence ◽  
Case Fatality ◽  
The United States ◽  
Invasive Group ◽  
Incidence Trends ◽  
Disease Case ◽  
Group A

Abstract Background Rates of invasive group A Streptococcus (iGAS) disease in the United States have risen since 2014; reasons remain unclear. Outbreaks of iGAS infection among persons experiencing homelessness (PEH) and persons who inject drugs in Europe, Canada, and the United States have been described. Using active, population-based surveillance data from California’s Emerging Infections Program, we describe incidence trends and characteristics of iGAS infection among PEH and persons not experiencing homelessness (PNEH) in San Francisco (SF) County during 2010–2017. Methods We defined an iGAS case as infection with GAS isolated from a normally sterile site (e.g., blood) in an SF resident. We calculated annual iGAS disease incidence rates (cases per 100,000 population) for PEH and PNEH using denominators from SF’s Department of Homelessness and Supportive Housing and the State of California Department of Finance. Demographic, clinical, and exposure characteristics of PEH and PNEH were compared by chi-square or t-test. Results We identified 673 iGAS cases in SF during 2010–2017. Among these, 34% (229/673) were among PEH. Annual iGAS incidence among PEH rose from ~300 (2010–2014) to 547 (95% CI: 379–714) per 100,000 in 2017 (P < 0.001, Cochran-Armitage trend test); rates peaked at 758 (95% CI: 561–955) in 2016. Annual iGAS incidence in PNEH rose from a mean of 5 in 2010–2013 to 9.3 (95% CI: 7.3–11.4) per 100,000 in 2017 (P < 0.001). Annual iGAS incidence in PEH was 42–72 times that in PNEH. PEH with iGAS infections were significantly younger and more likely to be male, white, and uninsured or enrolled in Medicaid (P < 0.05 for each) compared with PNEH with iGAS disease. Case fatality ratios, ICU admission, infection type, and length of hospital stay did not differ significantly. Smoking, current injection drug use, current alcohol abuse, and AIDS diagnosis were significantly more common among PEH with iGAS. Obesity, diabetes, and cancer were significantly more common among PNEH with iGAS. Conclusion In San Francisco, iGAS rates among both PEH and PNEH have risen significantly. Incidence of iGAS is strikingly higher in PEH than in PNEH and exposures differed between PEH and PNEH with iGAS. This information could inform development of disease control and prevention strategies. Disclosures All authors: No reported disclosures.

scholarly journals Elevated risk of invasive group A streptococcal disease and host genetic variation in the human leucocyte antigen locus

2019 ◽  
Vol 21 (1) ◽  
pp. 63-70
Author(s):  
Tom Parks ◽  
Katherine Elliott ◽  
Theresa Lamagni ◽  
Kathryn Auckland ◽  
Alexander J. Mentzer ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Human Leucocyte Antigen ◽  
Elevated Risk ◽  
Invasive Group ◽  
Streptococcal Disease ◽  
Group A ◽  
Host Genetic

scholarly journals Identification of risk and protective human leukocyte antigens in COVID-19 using genotyping and structural modeling

2021 ◽  
Author(s):  
Yiran Shen ◽  
David Ostrov ◽  
Santosh Rananaware ◽  
Piyush K Jain ◽  
Cuong Nguyen
Keyword(s):  
Immune Deficiency ◽  
Immune Responses ◽  
Human Leukocyte ◽  
Hla Typing ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Leukocyte Antigens ◽  
Disease Mechanisms ◽  
Unknown Risk ◽  
Increased Risk

COVID-19 is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The severity of COVID-19 is highly variable and related to known (e.g., age, obesity, immune deficiency) and unknown risk factors. Since innate and adaptive immune responses are elicited in COVID-19 patients, we genotyped 94 Florida patients with confirmed COVID-19 and 89 healthy controls. We identified an HLA gene, HLA-DPA1, in which specific alleles were associated with the risk of SARS-CoV-2 positivity and COVID-19 disease. HLA-DPA1*01:03 was associated with reduced incidence of SARS-CoV-2 positivity, whereas HLA-DPA1*03:01 was associated with increased risk of SARS-CoV-2 positivity. These data suggest a model in which COVID-19 severity is influenced by immunodominant peptides derived from SARS-CoV-2 preferentially presented by specific HLA-DP molecules to either protective (for asymptomatic COVID-19) or pathogenic T cells (in severe COVID-19). Although this study is limited to comparing SARS-CoV-2 positive and negative subjects, these data suggest that HLA typing of COVID-19 patients stratified for disease severity may be informative for identifying biomarkers and disease mechanisms in high-risk individuals

scholarly journals SweHLA: the high confidence HLA typing bio-resource drawn from 1000 Swedish genomes

2019 ◽  
Vol 28 (5) ◽  
pp. 627-635 ◽  
Author(s):  
Jessika Nordin ◽  
Adam Ameur ◽  
Kerstin Lindblad-Toh ◽  
Ulf Gyllensten ◽  
Jennifer R. S. Meadows
Keyword(s):  
Human Leukocyte ◽  
Class Ii ◽  
Hla Typing ◽  
Class I ◽  
Sequencing Data ◽  
High Confidence ◽  
Leukocyte Antigen ◽  
Hla Dqa1 ◽  
Inference Methods ◽  
Ngs Data

AbstractThere is a need to accurately call human leukocyte antigen (HLA) genes from existing short-read sequencing data, however there is no single solution that matches the gold standard of Sanger sequenced lab typing. Here we aimed to combine results from available software programs, minimizing the biases of applied algorithm and HLA reference. The result is a robust HLA population resource for the published 1000 Swedish genomes, and a framework for future HLA interrogation. HLA 2nd-field alleles were called using four imputation and inference methods for the classical eight genes (class I: HLA-A, HLA-B, HLA-C; class II: HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRB1). A high confidence population set (SweHLA) was determined using an n−1 concordance rule for class I (four software) and class II (three software) alleles. Results were compared across populations and individual programs benchmarked to SweHLA. Per gene, 875 to 988 of the 1000 samples were genotyped in SweHLA; 920 samples had at least seven loci called. While a small fraction of reference alleles were common to all software (class I = 1.9% and class II = 4.1%), this did not affect the overall call rate. Gene-level concordance was high compared to European populations (>0.83%), with COX and PGF the dominant SweHLA haplotypes. We noted that 15/18 discordant alleles (delta allele frequency >2) were previously reported as disease-associated. These differences could in part explain across-study genetic replication failures, reinforcing the need to use multiple software solutions. SweHLA demonstrates a way to use existing NGS data to generate a population resource agnostic to individual HLA software biases.

scholarly journals Invasive group A streptococcal infections in the San Francisco Bay area, 1989–99

2002 ◽  
Vol 129 (3) ◽  
pp. 471-478 ◽  
Author(s):  
D. J. PASSARO ◽  
D. S. SMITH ◽  
E. C. HETT ◽  
A. L. REINGOLD ◽  
P. DAILY ◽  
...  
Keyword(s):  
Native Americans ◽  
San Francisco ◽  
San Francisco Bay ◽  
San Francisco Bay Area ◽  
Case Fatality ◽  
Population Based ◽  
Emerging Infections ◽  
Invasive Group ◽  
Bay Area ◽  
Group A

To describe the epidemiology of invasive group A streptococcal (iGAS) infections in the San Francisco Bay Area, population-based active surveillance for laboratory-confirmed iGAS was conducted by the California Emerging Infections Program in three California counties. From January 1989 to December 1999, 1415 cases of iGAS were identified. Mean iGAS incidence was 4·06/100 000 person-years and case fatality ratio was 13%, with no linear trends over time. Incidence was lowest in adolescents, was higher in men than women (4·4 vs. 3·2/100 000 person-years), and was higher in African–Americans (6·7) than in non-Hispanic (4·1) or Hispanic (3·4) Whites, Asians (2·2) or Native Americans (1·7/100 000 person-years). Injecting drug use was the riskiest underlying condition and was associated with the highest attributable risk. Cases were associated with several underlying conditions, but 23% occurred in previously healthy persons. From 1989–1999, iGAS infections in the San Francisco Bay Area became neither more common nor more deadly.

scholarly journals 462. Prospective Surveillance of Invasive Group A Streptococcal Infections in Toronto, Ontario, Canada: 1992–2017

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S226-S227
Author(s):  
Christopher Kandel ◽  
Nick Daneman ◽  
Walter Demczuk ◽  
Wayne Gold ◽  
Karen Green ◽  
...  
Keyword(s):  
Case Fatality ◽  
Clinical Information ◽  
Population Based ◽  
Incidence Rates ◽  
Invasive Group ◽  
Bacterial Diseases ◽  
Central Processing ◽  
Common Clinical Presentation ◽  
Group A ◽  
Over Time

Abstract Background. Background Invasive Group A streptococcal (iGAS) infections remain a substantial source of morbidity and mortality. We explore the clinical and molecular epidemiology of iGAS infections in Toronto, Ontario, Canada over a 26-year period. Methods The Toronto Invasive Bacterial Diseases Network has performed population-based surveillance for iGAS infections in metropolitan Toronto and Peel regions since 1992. Participating microbiology laboratories report and submit sterile site specimens for central processing. M typing was performed on iGAS isolates until September 2006; thereafter emm typing was performed. Clinical information was collected by chart review using standardized collection forms. Results Over the 26-year period there were 2819 iGAS infections, representing an average incidence of 2.85 per 100,000 residents with a nadir of 1.65 in 1993 and a peak of 4.52 in 2014. Nosocomial infections occurred in 8.9% (251/2,819). There was substantial variation in annual incidence rates over the study period with increases from 1992 until 2002 and then 2004 until 2014 (analysis for trend, P < 0.001). Skin and soft-tissue infections were the most common clinical presentation, accounting for 33.2% (936/2,819), followed by bacteremia without a focus in 15.4% (435/2,819). Necrotizing fasciitis was observed in 7.4% (208/2,819) and criteria for toxic shock syndrome were met in 17.6% (497/2,819). Overall case fatality within 30 days of hospitalization was 15.3% (95% confidence interval 14.0 to 16.6) and did not change over time. M serotype distribution varied yearly with the most common type being M1 at 22.2% (626/2,189) followed by M12 at 8.2% (230/2,189), then M89 at 5.8% (163/2,189). Antibiotic susceptibility was available from 1998 onwards with overall clindamycin susceptibility at 92.3% (1,957/2,121) and erythromycin susceptibility at 87.9% (1864/2,121). Conclusion The incidence of iGAS in Toronto, Ontario has varied over time, with no recent increase apparent. Similar to worldwide observations, M1 serotype was the most commonly isolated; most common serotypes demonstrated cyclical variation. Case fatality rates have remained relatively constant making the development of a vaccine imperative. Disclosures All authors: No reported disclosures.

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