Cluster detection with random neighbourhood covering: Application to invasive Group A Streptococcal disease.
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ABSTRACT:
SUBMITTER: Cavallaro M
PROVIDER: S-EPMC9744322 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
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Cluster detection with random neighbourhood covering: Application to invasive Group A Streptococcal disease.
Cavallaro Massimo M Coelho Juliana J Ready Derren D Decraene Valerie V Lamagni Theresa T McCarthy Noel D ND Todkill Dan D Keeling Matt J MJ
PLoS computational biology 20221130 11
The rapid detection of outbreaks is a key step in the effective control and containment of infectious diseases. In particular, the identification of cases which might be epidemiologically linked is crucial in directing outbreak-containment efforts and shaping the intervention of public health authorities. Often this requires the detection of clusters of cases whose numbers exceed those expected by a background of sporadic cases. Quantifying exceedances rapidly is particularly challenging when on ...[more]
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Project description:BackgroundThe development of vaccines and evaluation of novel treatment strategies for invasive group A streptococcal (iGAS) disease requires suitable models of human infection that can be monitored longitudinally and are preferably non-invasive. Bio-photonic imaging provides an opportunity to reduce use of animals in infection modelling and refine the information that can be obtained, however the range of bioluminescent GAS strains available is limited. In this study we set out to develop bioluminescent iGAS strains for use in in vivo pneumonia and soft tissue disease models.ResultsUsing clinical emm1, emm3, and emm89 GAS strains that were transformed with constructs carrying the luxABCDE operon, growth and bioluminescence of transformed strains were characterised in vitro and in vivo. Emm3 and emm89 strains expressed detectable bioluminescence when transformed with a replicating plasmid and light production correlated with viable bacterial counts in vitro, however plasmid instability precluded use in the absence of antimicrobial pressure. Emm89 GAS transformed with an integrating construct demonstrated stable bioluminescence that was maintained in the absence of antibiotics. Bioluminescence of the emm89 strain correlated with viable bacterial counts both in vitro and immediately following infection in vivo. Although bioluminescence conferred a detectable fitness burden to the emm89 strain during soft tissue infection in vivo, it did not prevent dissemination to distant tissues.ConclusionDevelopment of stably bioluminescent GAS for use in vitro and in vivo models of infection should facilitate development of novel therapeutics and vaccines while also increasing our understanding of infection progression and transmission routes.
| S-EPMC6006931 | biostudies-literature
Project description:Whole-genome analysis was applied to investigate atypical point-source transmission of 2 invasive group A streptococcal (GAS) infections. Isolates were serotype M4, ST39, and genetically indistinguishable. Comparison with MGAS10750 revealed nonsynonymous polymorphisms in ropB and increased speB transcription. This study demonstrates the usefulness of whole-genome analyses for GAS outbreaks.
| S-EPMC4800461 | biostudies-literature
Project description:Group A streptococcus (GAS) is an important human pathogen that produces several extracellular exotoxins to facilitate invasion and infection. Streptococcal pyrogenic exotoxin B (SPE B) has been demonstrated to be an important virulence factor of GAS. Our previous studies indicate that SPE B cleaves complement 3 (C3) and inhibits the activation of complement pathways. In this study, we constructed and expressed recombinant fragments of SPE B to examine the C3-binding site of SPE B. Using enzyme-linked immunosorbent assays and pull-down assays, we found that the C-terminal domain, containing amino-acid residues 345-398, of SPE B was the major binding site of human serum C3. We further identified a major, Ala376-Pro398, and a minor C3-binding motif, Gly346-Gly360, that both mediated the binding of C3 complement. Immunization with the C3-binding motifs protected mice against challenge with a lethal dose of non-invasive M49 strain GAS but not invasive M1 strains. To achieve higher efficiency against invasive M1 GAS infection, a combination of synthetic peptides derived from C-terminal epitope of streptolysin S (SLSpp) and from the major C3-binding motif of SPE B (PP6, Ala376-Pro398) was used to elicit specific immune response to those two important streptococcal exotoxins. Death rates and the severity of skin lesions decreased significantly in PP6/SLSpp-immunized mice that were infected with invasive M1 strains of GAS. These results indicate a combination of the C3-binding motif of SPE B and the protective epitope of SLS could be used as a subunit vaccine against invasive M1 strains group A streptococcal infection.
| S-EPMC4309557 | biostudies-literature
Project description:ObjectivesGroup B streptococcus (GBS) infection is a serious disease that continues to cause high morbidity and mortality. It is one of the leading cause of sepsis; particularly meningitis, in infants and young children all around the world. In this study, we aim to identify the incidence of GBS sepsis in Omani infants less than 3 months of age who were born at Royal Hospital and who presented with clinical sepsis and positive culture. In addition, we aim to describe the clinical presentation and complications noted on admission and then on follow-up visit.MethodsThis is an observational retrospective chart review study. It included all Omani infants (0-3 months) who were diagnosed to have GBS sepsis/meningitis from 2006 to 2016 at the Royal Hospital, Muscat, Sultanate of Oman.ResultsThere were 83,000 live births in the Royal Hospital over a period of 10 years. Thirty-eight babies had culture proven GBS infection, with an overall incidence rate of neonatal GBS of 0.46 per 1000 live births with 95% confidence intervals. There were no significant variations in the annual rates of infection during the study period, ranging from around 1-7 cases per year. Additional 5 cases of GBS sepsis presented to Royal Hospital are either through Emergency Department or as referrals from other hospitals, giving us a total of 43 cases of proven GBS infections. Out of the 43 cases, 8 were born prematurely (19%), either before (<34 weeks, n = 2) or during (34-36 weeks, n = 6). Term babies were 35 out of 43 with percentage of 81% of the total. Three died, resulting in a case mortality of 7.0%.ConclusionOur GBS incidence is comparable to that of screened population internationally. At the time being, with the best available results, maternal screening might not seem cost effective in our current settings. A cost effective study is required before implemented a national screening programme in the Country. However, this research will definitely help in the process of any future plans of implantation of new guidelines, as it can be used as leading point for future prospective studies.
| S-EPMC7567995 | biostudies-literature
Project description:Data on neonatal group B streptococcal (GBS) invasive disease burden are needed to refine prevention policies. Differences in surveillance methods and investigating for cases can lead to varying disease burden estimates. We compared the findings of laboratory-based passive surveillance for GBS disease across South Africa, and for one of the provinces compared this to a real-time, systematic, clinical surveillance in a population-defined region in Johannesburg, Soweto. Passive surveillance identified a total of 799 early-onset disease (EOD, <7 days age) and 818 LOD (late onset disease, 7-89 days age) cases nationwide. The passive surveillance provincial incidence varied for EOD (range 0.00 to 1.23/1000 live births), and was 0.03 to 1.04/1000 live births for LOD. The passive surveillance rates for Soweto, were not significantly different compared to those from the systematic surveillance (EOD 1.23 [95%CI 1.06-1.43] vs. 1.50 [95%CI 1.30-1.71], respectively, rate ratio 0.82 [95%CI 0.67-1.01]; LOD 1.04 [95% CI 0.90-1.23] vs. 1.22 [95%CI 1.05-1.42], rate ratio 0.85 [95% CI 0.68-1.07]). A review of the few cases missed in the passive system in Soweto, suggested that missing key identifiers, such as date of birth, resulted in their omission during the electronic data extraction process. Our analysis suggests that passive surveillance provides a modestly lower estimate of invasive GBS rates compared to real time sentinel-site systematic surveillance, however, this is unlikely to be the reason for the provincial variability in incidence of invasive GBS disease in South Africa. This, possibly reflects that invasive GBS disease goes undiagnosed due to issues related to access to healthcare, poor laboratory capacity and varying diagnostic procedures or empiric antibiotic treatment of neonates with suspected sepsis in the absence of attempting to making a microbiological diagnosis. An efficacious GBS vaccine for pregnant women, when available, could be used as a probe to better quantify the burden of invasive GBS disease in low-middle resourced settings such as ours. From our study passive systems are important to monitor trends over time as long as they are interpreted with caution; active systems give better detailed information and will have greater representivity when expanded to other surveillance sites.
| S-EPMC4824385 | biostudies-literature
Project description:Viridans group streptococci (VGS) are a heterogeneous group of medically important bacteria that cannot be accurately assigned to a particular species using conventional phenotypic methods. Although multilocus sequence analysis (MLSA) is considered the gold standard for VGS species-level identification, MLSA is not yet feasible in the clinical setting. Conversely, molecular methods, such as sodA and 16S rRNA gene sequencing, are clinically practical but not sufficiently accurate for VGS species-level identification. Here, we present data regarding the use of an ∼ 400-nucleotide internal fragment of the gene encoding DNA gyrase subunit B (GyrB) for VGS species-level identification. MLSA, internal gyrB, sodA, full-length, and 5' 16S gene sequences were used to characterize 102 unique VGS blood isolates collected from 2011 to 2012. When using the MLSA species assignment as a reference, full-length and 5' partial 16S gene and sodA sequence analyses failed to correctly assign all strains to a species. Precise species determination was particularly problematic for Streptococcus mitis and Streptococcus oralis isolates. However, the internal gyrB fragment allowed for accurate species designations for all 102 strains. We validated these findings using 54 VGS strains for which MLSA, 16S gene, sodA, and gyrB data are available at the NCBI, showing that gyrB is superior to 16S gene and sodA sequence analyses for VGS species identification. We also observed that specific polymorphisms in the 133-amino acid sequence of the internal GyrB fragment can be used to identify invasive VGS species. Thus, the GyrB amino acid sequence may offer a more practical and accurate method for classifying invasive VGS strains to the species level.
| S-EPMC4136163 | biostudies-literature
Project description:PurposeInvasive Group G streptococcal infection (iGGS) has increasingly been recognized as a cause of severe disease, mainly among elderly people with chronic illnesses. This study aimed to examine age-related differences in clinical characteristics of iGGS and describe its characteristics among very elderly individuals (≥80 years).MethodsFifty-four iGGS patients for whom detailed clinical information was available were identified from 2002 to 2014 in a tertiary care hospital in Japan. iGGS (n = 54) was compared with invasive Group A (iGAS; n = 17) and B streptococcal infection patients (iGBS; n = 52) based on patient age.ResultsThe incidence of iGGS in our catchment area significantly increased during the study period. The prevalence of iGGS in the very elderly population was higher than that of iGAS or iGBS (p<0.001). Among iGGS patients, cardiovascular disease, chronic kidney disease, oxygen demand, and bacteremia with unknown focus of infection were more frequent in the very elderly population (p = 0.009, p = 0.02, p = 0.04, and p = 0.04, respectively). Altered mental status was present in half of iGGS patients aged ≥60 years (p = 0.03). In contrast, alcohol drinking and liver cirrhosis were significantly more frequent in patients with iGGS aged <60 years than in other age groups (p<0.001, p = 0.001, respectively). Levofloxacin resistance in GBS isolates was significantly more frequent among very elderly patients than among other age groups (p<0.001).ConclusionsThe burden of iGGS has been increasing in our catchment area. Different iGGS-associated clinical characteristics were found in each age group. Unclear and atypical clinical manifestations and syndromes were likely to be observed in very elderly patients. Alcohol drinking and liver cirrhosis may contribute to iGGS even in patients aged <60 years. Understanding these age-related differences could be helpful for optimal diagnosis and treatment.
| S-EPMC6405256 | biostudies-literature
Project description:BACKGROUND:Invasive Group A Streptococcal (iGAS) disease exerts an important burden among Australian children. No Australian hospitalisation cost estimates for treating children with iGAS disease exist, so the financial impact of this condition is unknown. AIM:To determine the minimum annual healthcare cost for children (< 18 years) hospitalised with iGAS disease in Australia from a healthcare sector perspective. METHODS:A cost analysis including children with laboratory-confirmed iGAS disease hospitalised at the Royal Children's Hospital (Victoria, Australia; July 2016 to June 2019) was performed. Results were extrapolated against the national minimum iGAS disease incidence. This analysis included healthcare cost from the 7 days prior to the index admission via General Practitioner (GP) and Emergency Department (ED) consultations; the index admission itself; and the 6 months post index admission via rehabilitation admissions, acute re-admissions and outpatient consultations. Additional extrapolations of national cost data by age group, Aboriginal and Torres Strait Islander ethnicity and jurisdiction were performed. RESULTS:Of the 65 included children, 35% (n = 23) were female, 5% (n = 3) were Aboriginal and Torres Strait Islander, and the average age was 4.4 years (SD 4.6; 65% aged 0-4). The iGAS disease related healthcare cost per child was $67,799 (SD $92,410). These costs were distributed across the 7 days prior to the index admission via GP and ED consultations (0.2 and 1.1% of total costs, respectively), the index admission itself (88.7% of the total costs); and the 6 months post index admission via rehabilitation admissions, acute re-admissions and outpatient consultations (5.3, 4.5 and 0.1% of total costs, respectively). Based on a national minimum paediatric incidence estimation of 1.63 per 100,000 children aged < 18 (95%CI: 1.11-2.32), the total annual healthcare cost for children with iGAS in 2019 was $6,200,862. The financial burden reflects the overrepresentation of Aboriginal and Torres Strait Islander people in the occurrence of iGAS disease. Costs were concentrated among children aged 0-4 years (62%). CONCLUSION:As these cost estimations were based on a minimum incidence, true costs may be higher. Strengthening of surveillance and control of iGAS disease, including a mandate for national notification of iGAS disease, is warranted. TRIAL REGISTRATION:The current study is a part of ongoing iGAS surveillance work across seven paediatric health services in Australia. As this is not a clinical trial, it has not undergone trial registration.
| S-EPMC8670128 | biostudies-literature
Project description:BackgroundIncreases in invasive group A streptococcal disease (iGAS) have recently been reported in multiple countries in the northern hemisphere, occurring during, and outside of, typical spring peaks. We report the epidemiology of iGAS among children in Australia from 1 July 2018 to 31 December 2022.MethodsThe Paediatric Active Enhanced Disease Surveillance (PAEDS) Network prospectively collected iGAS patient notifications for children and young people aged less than 18 years admitted to five major Australian paediatric hospitals in Victoria, Queensland, Western Australia and the Northern Territory. Patients were eligible for inclusion if they had GAS isolated from a normally sterile body site, or met clinical criteria for streptococcal toxic shock syndrome or necrotising fasciitis with GAS isolated from a non-sterile site. We report patients' clinical and demographic characteristics, and estimate minimum incidence rates.FindingsWe identified 280 paediatric iGAS patients, median age 4.5 years (interquartile range 1.4-6.4). We observed a pre-pandemic peak annualised incidence of 3.7 per 100,000 (95% CI 3.1-4.4) in the 3rd quarter of 2018, followed by a decline to less than 1.0 per 100,000 per quarter from 2020 to mid-2021. The annualised incidence increased sharply from mid-2022, peaking at 5.2 per 100,000 (95% CI 4.4-6.0) in the 3rd quarter and persisting into the 4th quarter (4.9 per 100,000, 95% CI 4.2-5.7). There were 3 attributable deaths and 84 (32%) patients had severe disease (overall case fatality rate 1%, 95% CI 0.2-3.3). Respiratory virus co-infection, positive in 57 of 119 patients tested, was associated with severe disease (RR 1.9, 95% CI 1.2-3.0). The most common emm-type was emm-1 (60 of 163 isolates that underwent emm-typing, 37%), followed by emm-12 (18%).InterpretationAustralia experienced an increase in the incidence of iGAS among children and young people in 2022 compared to pandemic years 2020-2021. This is similar to northern hemisphere observations, despite differences in seasons and circulating respiratory viruses. Outbreaks of iGAS continue to occur widely. This emphasises the unmet need for a vaccine to prevent significant morbidity associated with iGAS disease.FundingMurdoch Children's Research Institute funded open access publishing of this manuscript.
| S-EPMC10786649 | biostudies-literature
Project description:Patients with severe group A Streptococcus (GAS) induced necrotizing soft tissue infection sometimes develop Streptococcal toxic shock syndrome, which is a life-threatening condition with an extremely high fatality rate. Obtaining survival is the most important goal; however, an early diagnosis for debridement surgery and quick granulation formation for skin grafting surgery can better preserve the extremity functions. The patient was a 47-year-old man with a history of atopic dermatitis who presented with GAS-induced necrotizing soft tissue infection in his left lower extremity. His vital signs indicated shock, and he was diagnosed with streptococcal toxic shock syndrome. Emergency surgery was performed with his body pressure maintained with noradrenaline. Intraoperatively, rapid antigen detection tests (RADTs) were negative in the medial thigh and positive in the lower leg, which helped in decision-making regarding the area of aggressive debridement surgery. The wound culture results matched the intraoperative rapid antigen detection test results. A collagen/gelatin sponge with the sustained release of basic fibroblast growth factor was used as an artificial dermis before skin grafting. Excellent granulation was obtained, and skin grafting surgery was performed on the 11th day after collagen/gelatin sponge placement. He was discharged home on the 42nd day with normal lower extremity functions. First, an intraoperative diagnosis using GAS-rapid antigen detection tests with an appropriate sampling method from small incisions avoided excessive surgical debridement. Second, collagen/gelatin sponge with the sustained release of basic fibroblast growth factor promoted quick granulation tissue formation for wound bed preparation. These efforts resulted in the successful less-invasive treatment of a patient with streptococcal toxic shock syndrome caused by GAS-induced necrotizing soft tissue infection.
| S-EPMC8432633 | biostudies-literature