Long-term healthcare utilisation, costs and quality of life after invasive group B Streptococcus disease: a cohort study in five low-income and middle-income countries.

INTRODUCTION: There are no published data on the long-term impact of invasive group B Streptococcus disease (iGBS) on economic costs or health-related quality of life (HRQoL) in low-income and middle-income countries. We assessed the impact of iGBS on healthcare utilisation, costs and HRQoL in Argentina, India, Kenya, Mozambique and South Africa. METHODS: Inpatient and outpatient visits, out-of-pocket (OOP) healthcare payments in the 12 months before study enrolment, and health-state utility of children and caregivers (using the EuroQol 5-Dimensions-3-Level) were collected from iGBS survivors and an unexposed cohort matched on site, age at recruitment and sex. We used logistic or Poisson regression for analysing healthcare utilisation and zero-inflated gamma regression models for family and health system costs. For HRQoL, we used a zero-inflated beta model of disutility pooled data. RESULTS: 161 iGBS-exposed and 439 unexposed children and young adults (age 1-20) were included in the analysis. Compared with unexposed participants, iGBS was associated with increased odds of any healthcare utilisation in India (adjusted OR 11.2, 95% CI 2.9 to 43.1) and Mozambique (6.8, 95% CI 2.2 to 21.1) and more frequent healthcare visits (adjusted incidence rate ratio (IRR) for India 1.7 (95% CI 1.4 to 2.2) and for Mozambique 6.0 (95% CI 3.2 to 11.2)). iGBS was also associated with more frequent days in inpatient care in India (adjusted IRR 4.0 (95% CI 2.3 to 6.8) and Kenya 6.4 (95% CI 2.9 to 14.3)). OOP payments were higher in the iGBS cohort in India (adjusted mean: Int$682.22 (95% CI Int$364.28 to Int$1000.16) vs Int$133.95 (95% CI Int$72.83 to Int$195.06)) and Argentina (Int$244.86 (95% CI Int$47.38 to Int$442.33) vs Int$52.38 (95% CI Int$-1.39 to Int$106.1)). For all remaining sites, differences were in the same direction but not statistically significant for almost all outcomes. Health-state disutility was higher in iGBS survivors (0.08, 0.04-0.13 vs 0.06, 0.02-0.10). CONCLUSION: The iGBS health and economic burden may persist for years after acute disease. Larger studies are needed for more robust estimates to inform the cost-effectiveness of iGBS prevention.

Burden of disease and productivity impact of Streptococcus suis infection in Thailand.

BACKGROUND: Streptoccocus suis (S.suis) infection is a neglected zoonosis disease in humans mainly affects men of working age. We estimated the health and economic burden of S.suis infection in Thailand in terms of years of life lost, quality-adjusted life years (QALYs) lost, and productivity-adjusted life years (PALYs) lost which is a novel measure that adjusts years of life lived for productivity loss attributable to disease. METHODS: A decision-analytic Markov model was developed to simulate the impact of S. suis infection and its major complications: death, meningitis and infective endocarditis among Thai people in 2019 with starting age of 51 years. Transition probabilities, and inputs pertaining to costs, utilities and productivity impairment associated with long-term complications were derived from published sources. A lifetime time horizon with follow-up until death or age 100 years was adopted. The simulation was repeated assuming that the cohort had not been infected with S.suis. The differences between the two set of model outputs in years of life, QALYs, and PALYs lived reflected the impact of S.suis infection. An annual discount rate of 3% was applied to both costs and outcomes. One-way sensitivity analyses and Monte Carlo simulation modeling technique using 10,000 iterations were performed to assess the impact of uncertainty in the model. KEY RESULTS: This cohort incurred 769 (95% uncertainty interval [UI]: 695 to 841) years of life lost (14% of predicted years of life lived if infection had not occurred), 826 (95% UI: 588 to 1,098) QALYs lost (21%) and 793 (95%UI: 717 to 867) PALYs (15%) lost. These equated to an average of 2.46 years of life, 2.64 QALYs and 2.54 PALYs lost per person. The loss in PALYs was associated with a loss of 346 (95% UI: 240 to 461) million Thai baht (US$11.3 million) in GDP, which equated to 1.1 million Thai baht (US$ 36,033) lost per person. CONCLUSIONS: S.suis infection imposes a significant economic burden both in terms of health and productivity. Further research to investigate the effectiveness of public health awareness programs and disease control interventions should be mandated to provide a clearer picture for decision making in public health strategies and resource allocations.

The economic and health burdens of diseases caused by group A Streptococcus in New Zealand.

OBJECTIVES: In preparation for the future arrival of a group A Streptococcus (GAS) vaccine, this study estimated the economic and health burdens of GAS diseases in New Zealand (NZ). METHODS: The annual incidence of GAS diseases was based on extrapolation of the average number of primary healthcare episodes managed each year in general practices (2014-2016) and on the average number of hospitalizations occurring each year (2005-2014). Disease incidence was multiplied by the average cost of diagnosing and managing an episode of disease at each level of care to estimate the annual economic burden. RESULTS: GAS affected 1.5% of the population each year, resulting in an economic burden of 29.2 million NZ dollars (2015 prices) and inflicting a health burden of 2373 disability-adjusted life years (DALYs). Children <5 years of age were the most likely age group to present for GAS-related healthcare. Presentations for superficial throat and skin infections (predominantly pharyngitis and impetigo) were more common than other GAS diseases. Cellulitis contributed the most to the total economic and health burdens. Invasive and immune-mediated diseases disproportionately contributed to the total economic and health burdens relative to their frequency of occurrence. CONCLUSION: Preventing GAS diseases would have substantial economic and health benefits in NZ and globally.

Cost Effectiveness of Latest Recommendations for Group B Streptococci Screening in the United States.

OBJECTIVE: To evaluate whether group B streptococci (GBS) screening using the 2010 guideline (screening at 35 0/7-37 6/7 weeks of gestation) compared with the 2019 guideline (screening at 36 0/7-37 6/7 weeks of gestation with re-screening of women with GBS-negative results 5 weeks later) was more cost effective. METHODS: We constructed a decision-analysis model to compare the outcome of GBS early-onset disease in a hypothetical cohort of 3,614,049 women at 35 0/7 weeks of gestation or greater (the number of live births in 2017 excluding births based on population frequency from 23 to 34 weeks of gestation, women with GBS bacteriuria during the current pregnancy, and those with a history of a previous neonate with GBS disease). We took both a health care and societal perspective and all costs were expressed in 2017 U.S. dollars. Effectiveness was based on neonatal quality-adjusted life years (QALYs) gained. An incremental cost-effectiveness ratio was estimated with a willingness to pay threshold set at $100,000/QALY. All model inputs were derived from the literature. One-way probability and cost sensitivity analysis were performed to investigate model assumptions. RESULTS: Screening at 36 0/7-37 6/7 weeks of gestation with re-screening of women with GBS-negative results if 5 weeks passed from culture to delivery resulted in a 6% increase in neonatal QALYs gained (2,162 vs 2,037), 12% fewer cases of neonatal death (30 vs 34), and a 10% estimated reduction in total societal health care expenditures related to GBS early-onset disease ($639 million vs $707 million) when compared with the 2010 strategy of only screening at 35 0/7-37 6/7 weeks of gestation. The 2019 approach was cost effective, with an incremental cost-effectiveness ratio of $43,205 per neonatal QALY gained. CONCLUSION: Screening at 36 0/7-37 6/7 weeks of gestation with a 5-week re-screening for women with GBS-negative results is more cost effective than past strategies used in the United States.

Economic and epidemiological impact of different intervention strategies for subclinical and clinical mastitis.

The objective of this study was to evaluate and compare different combinations of intervention strategies for contagious or opportunistic subclinical and clinical intramammary infections (IMI). We simulated two different Danish dairy cattle herds with ten different intervention strategies focusing on cow-specific treatment or culling, including three baseline strategies without subclinical interventions. In one herd, the main causative pathogen of IMI was Staphylococcus (S.) aureus. In the other herd, Streptococcus (St.) agalactiae was the main causative agent. For both herds, we investigated costs and effectiveness of all ten intervention strategies. Intervention strategies consisted of measures against clinical and subclinical IMI, with baselines given by purely clinical intervention strategies. Our results showed that strategies including subclinical interventions were more cost-effective than the respective baseline strategies. Increase in income and reduction of IMI cases came at the cost of increased antibiotic usage and an increased culling rate in relation to IMI. However, there were differences between the herds. In the St. agalactiae herd, the clinical intervention strategy did not seem to have a big impact on income and number of cases. However, intervention strategies which included cow-specific clinical interventions led to a higher income and lower number of cases in the S. aureus herd. The results show that intervention strategies including interventions against contagious or opportunistic clinical and subclinical IMI can be highly cost-effective, but should be herd-specific.

Burden of disease and economic impact of human Streptococcus suis infection in Viet Nam.

BACKGROUND: Streptococcus suis is a zoonotic disease mainly affecting men of working age and can result in death or long-term sequelae, including severe hearing loss and vestibular dysfunction. We aimed to quantify the burden of disease and economic impact of this infection in Viet Nam. METHODS: The annual disease incidence for the period 2011-2014 was estimated based on surveillance data using a multiple imputation approach. We calculated disease burden in disability-adjusted life years (DALYs) and economic costs using an incidence-based approach from a patient's perspective and including direct and indirect impacts of S. suis infection and its long-term sequelae. RESULTS: The estimated annual incidence rate was 0.318, 0.324, 0.255 and 0.249 cases per 100 000 population in 2011, 2012, 2013 and 2014, respectively. The corresponding DALYs lost were 1832, 1866, 1467 and 1437. The mean direct cost per episode was US$1635 (95% confidence interval 1352-1923). The annual direct cost was US$370 000-500 000 and the indirect cost was US$2.27-2.88 million in this time period. CONCLUSIONS: This study showed a large disease burden and high economic impact of S. suis infection and provides important data for disease monitoring and control.

Point-of-Care Intrapartum Group B Streptococcus Molecular Screening: Effectiveness and Costs.

OBJECTIVE: To assess outcomes and costs associated with around-the-clock point-of-care intrapartum group B streptococcus (GBS) polymerase chain reaction (PCR) screening. METHODS: Intrapartum PCR screening was implemented in 2010. Intrapartum PCR was compared with antenatal culture screening in an uncontrolled, single institution, preintervention and postintervention study. The study periods included 4 years before and 6 years after the intervention, commencing in 2006 and concluding in 2015. The primary outcome measure was rate of early-onset neonatal GBS disease. Secondary outcomes included length of stay, days of antibiotics, and costs. RESULTS: During the 4 years of antenatal culture screening, 11,226 deliveries were recorded compared with 18,835 in the 6 years of intrapartum GBS PCR screening, corresponding to 11,818 and 18,980 live births, respectively. During the antenatal culture period, 3.8% of term deliveries did not undergo GBS testing compared with 0.1% during the intrapartum PCR period (P<.001). Between the two periods, the rate of proven early-onset GBS disease cases decreased from 1.01/1,000 to 0.21/1,000 (P=.026) and probable early-onset GBS disease cases from 2.8/1,000 to 0.73/1,000 (P<.001); the risk ratio for both was 0.25, 95% CI (0.14-0.43). Total days of hospital and antibiotic therapy for early-onset GBS disease declined by 64% and 60%, respectively, with no significant difference for average length of stay or antibiotic duration preintervention and postintervention. The yearly cost of delivery and treatment of newborns with GBS infection was reduced from $41,875±6,823 to $11,945±10,303 (P<.001). The estimated extra cost to avoid one early-onset GBS disease was $5,819. CONCLUSION: Point-of-care intrapartum GBS PCR screening was associated with a significant decrease in the rate of early-onset GBS disease and antibiotic use in newborns. The additional PCR costs were offset in part by the reduction in early-onset GBS disease treatment costs.

Economic appraisal of vaccination against Streptoccocus agalactiae in Nile tilapia farms in Brazil.

Infection with Streptococcus agalactiae causes mortality and major economic losses in Nile tilapia (Oreochromis niloticus) farming worldwide. In Brazil, serotype strains Ia, Ib and III have been isolated in streptococcosis outbreaks, but serotype Ib is the most prevalent. Vaccination is considered an effective method to prevent economically-important diseases in aquaculture and has been associated with decreased use of antibiotics and improvements in fish survival. We developed a flexible partial-budget model to undertake an economic appraisal of vaccination against Streptococcus agalactiae in Nile tilapia farmed in net cages in large reservoirs. The model considers the benefits and costs that are likely to be associated with vaccination at the farm-level, in one production cycle. We built three epidemiological scenarios of cumulative mortality attributable to S. agalactiae (5%, 10%, and 20%, per production cycle) in a non-vaccinated farm. For each scenario, we applied a stochastic model to simulate the net return of vaccination, given a combination of values of "vaccine efficacy", "gain in feed conversion ratio", "feed price", "fish market price ", and "cost of vaccine dose". In the 20% cumulative mortality scenario, the net return would break-even (benefits ≥ costs) in at least 97.9% of interactions. Should cumulative mortality be lower than 10%, the profitability of vaccination would be more dependent on better feed conversion ratio. The inputs "feed price" and "cost of vaccine" had minor effects on the output, in all pre-vaccination mortality scenarios. Although our simulations are based on conservative values and consider uncertainty about the modeled parameters, we conclude that vaccination against S. agalactiae is likely to be profitable in Nile tilapia farms, under similar production conditions.

The burden of infant group B streptococcal infections in Ontario: Analysis of administrative data to estimate the potential benefits of new vaccines.

Group B streptococcus (GBS) is a leading bacterial cause of neonatal sepsis and meningitis in many countries as well as an important cause of disease in pregnant women. Currently, serotype-specific conjugate vaccines are being developed. We conducted an epidemiological analysis of health administrative data to estimate the burden of infant GBS disease in Ontario, Canada and combined these estimates with literature on serotype distribution to estimate the burden of disease likely to be vaccine-preventable. Between 1st January 2005 and 31st December 2015, 907 of 64320 health care encounters in Ontario in patients under 1 year old had codes specifically identifying GBS as the cause of the disease, of which 717 were under one month of age. In addition, application of epidemiological data to the remaining patients allowed us to estimate a further 2322 cases and among them 1822 were under one month of age. In the same period, 579 confirmed neonatal invasive GBS cases in patients up to one month of age were reported to public health. Depending on serotype distribution, vaccination coverage and early versus late onset disease (0-6 days and 7-90 days of age respectively), the preventable fraction ranged widely. With a vaccine that is 90% effective and 60% immunization coverage, up to 52% of early and late onset disease could be prevented by forthcoming vaccines. GBS is under-reported in Ontario. Uncertainty about the potential impact of vaccine indicates that further analysis and research may be needed to prepare for policy-decision making, including clinical validation studies and an economic evaluation of GBS vaccination in Ontario.

Cost-effectiveness analysis of maternal immunisation against group B Streptococcus (GBS) disease: A modelling study.

BACKGROUND: There is a considerable global burden of invasive group B streptococcal (GBS) disease. Vaccines are being developed for use in pregnant women to offer protection to neonates. OBJECTIVE: To estimate the potential impact and cost-effectiveness of maternal immunisation against neonatal and maternal invasive GBS disease in the UK. METHODS: We developed a decision-tree model encompassing GBS-related events in infants and mothers, following a birth cohort with a time horizon equivalent to average life expectancy (81 years). We parameterised the model using contemporary data from disease surveillance and outcomes in GBS survivors. Costs were taken from NHS sources and research studies. Maternal immunisation in combination with risk-based intrapartum antibiotic prophylaxis (IAP) was compared to the current standard practice of risk-based IAP alone from an NHS and Personal Social Services (health-provider) perspective. We estimated the cases averted and cost per QALY gained through vaccination. One-way sensitivity analysis, scenario analysis and probabilistic sensitivity analysis were performed. RESULTS: An effective maternal immunisation programme could substantially reduce the burden of GBS disease. The deterministic analysis estimated the threshold cost-effective price for a GBS vaccine to be £54 per dose at £20,000/QALY (£71 per dose at £30,000/QALY). Results were most sensitive to assumptions on disease incidence, sequelae rate and vaccine efficacy. Probabilistic analysis showed 90.66% of iterations fell under the £30,000 threshold at a vaccine price of £55. Inclusion of modest prevention of stillbirths and/or, preterm births, carer health impacts, maternal GBS deaths and 1.5% discounting improved cost-effectiveness compared to the base case. Lowering vaccine strain coverage made the vaccine less cost-effective. A key limitation is that the properties of the final GBS vaccine are unknown. CONCLUSIONS: Maternal GBS immunisation is expected to be cost-effective, even at a relatively high vaccine price.

An economic case for a vaccine to prevent group A streptococcus skin infections.

BACKGROUND: Group A streptococcus (GAS) causes an exceptionally diverse range of diseases, raising questions about the optimal product characteristics of a commercially viable vaccine. The objectives of this study were to (1) estimate the current health and economic burdens caused by 24 diseases attributable to GAS each year in Australia and (2) use these estimates to explore the value of a GAS vaccine for different clinical indications, age schedules, and population groups. METHODS: For objective 1, we estimated the population heath and economic burdens by synthesising data from administrative databases, nationally representative surveys, literature reviews, public reimbursement schedules, and expert opinion. For objective 2, we modelled the prospective lifetime burden of GAS for all infants from birth, for children from 5 years of age, and for adults from 65 years of age. A vaccine was assumed to reduce each GAS disease by 70% for a period of 10 years, and the difference in outcomes between vaccinated and non-vaccinated cohorts were used to calculate the cost-effective value of vaccination. RESULTS: The annual health and economic burdens of GAS diseases totalled 23,528 disability-adjusted life years and AU$185.1 million in healthcare costs respectively; approximately half of each measure was due to cellulitis, followed by other skin infections and throat infections. Reducing the incidence of throat infections, skin infections, and cellulitis in non-Indigenous cohorts resulted in 30%, 33%, and 28% of the total vaccine value for an infant schedule (cost-effective vaccine price AU$260 per course); 47%, 26%, and 22% of the value for a child schedule (AU$289); and 2%, 15% and 74% for an adult schedule (AU$489). CONCLUSIONS: A vaccine that prevents GAS cellulitis and other skin infections, in addition to throat infections, would maximise its value and commercial viability, with a cost-effective price in line with other recently-licensed and funded vaccines in Australia.

Streptococcosis in Commercial and Noncommercial Avian Species in California: 95 Cases (2000-2017).

Streptococcal bacterial species represent common inhabitants of the intestinal tract of animals and humans with a potential for opportunistic infections. Streptococcosis has been identified in turkey poults ( Meleagris gallopavo), ducklings and goslings (Anatidae), broiler chickens, semimature-adult chickens ( Gallus gallus domesticus), and young and adult pigeons (Columbidae). However, the exact underlying factors that lead to bacterial invasion of the blood stream and tissue colonization have not been completely elucidated. The electronic database of the California Animal Health and Food Safety laboratory (Fresno, Tulare, and Turlock branches) was searched for necropsy cases in which streptococcosis was diagnosed in different avian species between January 2000 and August 2017. A total of 95 cases, involving both commercial operations and noncommercial premises, were analyzed. Streptococcus spp., Streptococcus bovis, and Streptococcus gallolyticus were identified from multiple organs, with macroscopic or histopathologic lesions (or both) indicative of septicemia in 23 (24%), 40 (42%), and 30 (32%) cases, respectively. Streptococcus pluranimalium and Streptococcus lutetiensis were also isolated from one (1%) and two (2%) cases, respectively. Turkey poults, broiler chickens, and ducklings were the most-commonly affected species with streptococcosis. Splenitis and hepatitis were the most-common lesions observed and these were the organs with the highest isolation rate. An overview of the clinical and pathologic presentation, and possible predisposing conditions associated with this bacterial infection, is provided.

Understanding the virulence of Streptococcus suis: A veterinary, medical, and economic challenge.

Streptococcus suis is a major swine pathogen worldwide and causes considerable economic losses in the swine industry. S. suis is also an emerging zoonotic agent, mainly in Asia. In pigs and humans, S. suis can cause septicemia, pneumonia, endocarditis, arthritis, and meningitis with irreversible sequelae. Identification and characterization of the virulence factors produced by S. suis are major advances in the understanding of the pathogenesis of S. suis infections and has therefore opened promising avenues for vaccine development against this pathogen. This literature review aimed to update the current knowledge of the virulence mechanisms of S. suis and of the vaccination strategies tested until now.

The cost of hospital care for management of invasive group A streptococcal infections in England.

The objective of this study was to estimate the direct financial costs of hospital care for management of invasive group A streptococcal (GAS) infections using hospital records for cases diagnosed in England. We linked laboratory-confirmed cases (n = 3696) identified through national surveillance to hospital episode statistics and reimbursement codes. From these codes we estimated the direct hospital costs of admissions. Almost all notified invasive GAS cases (92% of 3696) were successfully matched to a primary hospital admission. Of these, secondary admissions (within 30 days of primary admission) were further identified for 593 (17%). After exclusion of nosocomial cases (12%), the median costs of primary and secondary hospital admissions were estimated by subgroup analysis as £1984-£2212 per case, totalling £4·43-£6·34 million per year in England. With adjustment for unmatched cases this equated to £4·84-£6·93 million per year. Adults aged 16-64 years accounted for 48% of costs but only 40% of cases, largely due to an increased number of surgical procedures. The direct costs of hospital admissions for invasive GAS infection are substantial. These estimated costs will contribute to a full assessment of the total economic burden of invasive GAS infection as a means to assess potential savings through prevention measures.

Cost-effectiveness of a potential group B streptococcal vaccine program for pregnant women in South Africa.

BACKGROUND: In low- and middle-income countries neonatal infections are important causes of infant mortality. Group B streptococcus (GBS) is a major pathogen. A GBS polysaccharide-protein conjugate vaccine, the only option that has the potential to prevent both early- and late-onset GBS disease, has completed Phase II trials. Screening-based intrapartum antibiotic prophylaxis (IAP) for pregnant women, an effective strategy in high-income countries, is often not practical in these settings. Risk factor-based IAP (RFB-IAP) for women with risk factors at delivery has had limited success in preventing neonatal infection. We evaluated the cost and health impacts of maternal GBS vaccination in South Africa. METHODS AND FINDINGS: We developed a decision-analytic model for an annual cohort of pregnant women that simulates the natural history of GBS disease in their infants. We compared four strategies: doing nothing, maternal GBS vaccination, RFB-IAP, and vaccination plus RFB-IAP. Assuming vaccine efficacy varies from 50% to 90% against covered serotypes and 75% of pregnant women are vaccinated, GBS vaccination alone prevents 30-54% of infant GBS cases compared to doing nothing. For vaccine prices between $10 and $30, and mid-range efficacy, its cost ranges from $676 to $2390 per disability-adjusted life-year (DALY) averted ($US 2010), compared to doing nothing. RFB-IAP alone, compared to doing nothing, prevents 10% of infant GBS cases at a cost of $240/DALY. Vaccine plus RFB-IAP prevents 48% of cases at a cost of $664-2128/DALY. CONCLUSIONS: Vaccination would substantially reduce the burden of infant GBS disease in South Africa and would be very cost-effective by WHO guidelines. RFB-IAP is also very cost-effective, but prevents only 10% of cases. Vaccination plus RFB-IAP is more effective and more costly than vaccination alone, and consistently very cost-effective.

PRImary care Streptococcal Management (PRISM) study: in vitro study, diagnostic cohorts and a pragmatic adaptive randomised controlled trial with nested qualitative study and cost-effectiveness study.

BACKGROUND: Antibiotics are still prescribed to most patients attending primary care with acute sore throat, despite evidence that there is modest benefit overall from antibiotics. Targeting antibiotics using either clinical scoring methods or rapid antigen detection tests (RADTs) could help. However, there is debate about which groups of streptococci are important (particularly Lancefield groups C and G), and uncertainty about the variables that most clearly predict the presence of streptococci. OBJECTIVE: This study aimed to compare clinical scores or RADTs with delayed antibiotic prescribing. DESIGN: The study comprised a RADT in vitro study; two diagnostic cohorts to develop streptococcal scores (score 1; score 2); and, finally, an open pragmatic randomised controlled trial with nested qualitative and cost-effectiveness studies. SETTING: The setting was UK primary care general practices. PARTICIPANTS: Participants were patients aged ≥ 3 years with acute sore throat. INTERVENTIONS: An internet program randomised patients to targeted antibiotic use according to (1) delayed antibiotics (control group), (2) clinical score or (3) RADT used according to clinical score. MAIN OUTCOME MEASURES: The main outcome measures were self-reported antibiotic use and symptom duration and severity on seven-point Likert scales (primary outcome: mean sore throat/difficulty swallowing score in the first 2-4 days). RESULTS: The IMI TestPack Plus Strep A (Inverness Medical, Bedford, UK) was sensitive, specific and easy to use. Lancefield group A/C/G streptococci were found in 40% of cohort 2 and 34% of cohort 1. A five-point score predicting the presence of A/C/G streptococci [FeverPAIN: Fever; Purulence; Attend rapidly (≤ 3 days); severe Inflammation; and No cough or coryza] had moderate predictive value (bootstrapped estimates of area under receiver operating characteristic curve: 0.73 cohort 1, 0.71 cohort 2) and identified a substantial number of participants at low risk of streptococcal infection. In total, 38% of cohort 1 and 36% of cohort 2 scored ≤ 1 for FeverPAIN, associated with streptococcal percentages of 13% and 18%, respectively. In an adaptive trial design, the preliminary score (score 1; n = 1129) was replaced by FeverPAIN (n = 631). For score 1, there were no significant differences between groups. For FeverPAIN, symptom severity was documented in 80% of patients, and was lower in the clinical score group than in the delayed prescribing group (-0.33; 95% confidence interval -0.64 to -0.02; p = 0.039; equivalent to one in three rating sore throat a slight rather than moderately bad problem), and a similar reduction was observed for the RADT group (-0.30; -0.61 to 0.00; p = 0.053). Moderately bad or worse symptoms resolved significantly faster (30%) in the clinical score group (hazard ratio 1.30; 1.03 to 1.63) but not the RADT group (1.11; 0.88 to 1.40). In the delayed group, 75/164 (46%) used antibiotics, and 29% fewer used antibiotics in the clinical score group (risk ratio 0.71; 0.50 to 0.95; p = 0.018) and 27% fewer in the RADT group (0.73; 0.52 to 0.98; p = 0.033). No significant differences in complications or reconsultations were found. The clinical score group dominated both other groups for both the cost/quality-adjusted life-years and cost/change in symptom severity analyses, being both less costly and more effective, and cost-effectiveness acceptability curves indicated the clinical score to be the most likely to be cost-effective from an NHS perspective. Patients were positive about RADTs. Health professionals' concerns about test validity, the time the test took and medicalising self-limiting illness lessened after using the tests. For both RADTs and clinical scores, there were tensions with established clinical experience. CONCLUSIONS: Targeting antibiotics using a clinical score (FeverPAIN) efficiently improves symptoms and reduces antibiotic use. RADTs used in combination with FeverPAIN provide no clear advantages over FeverPAIN alone, and RADTs are unlikely to be incorporated into practice until health professionals' concerns are met and they have experience of using them. Clinical scores also face barriers related to clinicians' perceptions of their utility in the face of experience. This study has demonstrated the limitation of using one data set to develop a clinical score. FeverPAIN, derived from two data sets, appears to be valid and its use improves outcomes, but diagnostic studies to confirm the validity of FeverPAIN in other data sets and settings are needed. Experienced clinicians need to identify barriers to the use of clinical scoring methods. Implementation studies that address perceived barriers in the use of FeverPAIN are needed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN32027234. SOURCE OF FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 6. See the NIHR Journals Library website for further project information.

Cost analysis of dental services needed before hematopoietic cell transplantation.

OBJECTIVE: Streptococcal bacteremia occurs during hematopoietic cell transplantation (HCT), and treatment of active oral disease may reduce this risk. The objective of this study was to determine the type, number, and costs of pre-transplantation dental procedures in this population. STUDY DESIGN: Data were collected retrospectively from the records of patients who were to undergo HCT. The type, number, and costs of dental procedures were determined based on median charges of MassHealth (the Medicaid program in Massachusetts) and also on the median "usual and customary" fees charged by dentists in Massachusetts. RESULTS: A total of 405 patients were evaluated. There were 243 men (60%) and 162 women, with a median age of 53 years. The median and average costs (in US dollars) of dental treatment before HCT were $275 and $384, respectively, for patients covered by MassHealth and $368 and $522, respectively, for those with private insurance, adjusted to 2012 levels. CONCLUSIONS: Dental evaluation before HCT is an economical way for patients to minimize the risk of localized infection and possibly reduce the risk of bacteremia that may prolong the length of hospitalization.

Cost-effectiveness analysis of rheumatic heart disease prevention strategies.

Rheumatic heart disease (RHD), secondary to group A streptococcal infection is endemic in the developing as well as parts of the developed world with significant costs to the patient, and to the healthcare system. We briefly review the prevalence and cost of RHD in developed and developing nations. We subsequently develop a Markov model to evaluate the cost-effectiveness of three strategies (vs standard no prevention) for preventing RHD in a developing world country: primary prophylaxis (throat swab to detect and subsequently treat group A streptococci as needed); primary prophylaxis (antibiotic prophylaxis for all) with benzathine penicillin G once monthly to all patients (ages 5-21 years) regardless of evidence of infection; and secondary prophylaxis with monthly only to those with echocardiographic evidence of early RHD. Our model suggests that echocardiographic screening and secondary prophylaxis is the best strategy although the strategies change depending on parameters used.

Reduction of the use of antimicrobial drugs following the rapid detection of Streptococcus agalactiae in the vagina at delivery by real-time PCR assay.

OBJECTIVE: To assess whether the determination of the presence of group B streptococci (GBS) in the vagina using a rapid polymerase chain reaction (PCR) assay at delivery was able to spare useless antimicrobial treatments, as compared with conventional culture at 34-38 weeks of gestation. DESIGN: Practical evaluation and prospective cost-effectiveness analysis. SETTING: A university hospital in France. POPULATION: A cohort of 225 women in labour at the University-Hospital of Saint-Etienne. METHODS: Each woman had a conventional culture performed at 34-38 weeks of gestation. At the beginning of labour, two vaginal swabs were sampled for rapid PCR testing and culture. The decision to prescribe a prophylactic antimicrobial treatment or not was taken according to the result of the PCR test. A comparative cost-effectiveness analysis of the two diagnostic strategies was carried out. MAIN OUTCOME MEASURES: Number of women receiving inadequate prophylactic antimicrobial drugs following each testing strategy, costs of PCR testing and culture, frequency of vaginal GBS, and diagnostic performance of the PCR test at delivery. RESULTS: The percentage of unnecessarily treated women was significantly reduced using the rapid test versus conventional culture (4.5 and 13.6%, respectively; P < 0.001). The rate of vaginal GBS at delivery was 12.5%. The incremental cost-effectiveness ratio (ICER) for each inadequate management avoided was €36 and €173 from the point of view of the healthcare system and hospital, respectively. CONCLUSIONS: The PCR assay reduced the number of inadequate antimicrobial treatments aimed to prevent the early onset of GBS disease. However, this strategy generates extra costs that must be put into balance with its clinical benefits.

Bioeconomic modeling of intervention against clinical mastitis caused by contagious pathogens.

The objective of this study was to assess the epidemiologic and economic consequences of intervention against contagious clinical mastitis during lactation. A bioeconomic model of intramammary infections (IMI) was used to simulate contagious spread of Staphylococcus aureus, Streptococcus uberis, and Streptococcus dysgalactiae, and an environmental spread of Escherichia coli IMI in a 100-cow dairy herd during 1 quota year. The costs of clinical IMI, subclinical IMI, and intervention were calculated into the total annual net costs of IMI during lactation per scenario and compared with a default scenario. Input parameter values were based on the scientific literature. The scenarios were 3-d intramammary lactational treatment (default), 5-d intramammary treatment, 5-d intramammary treatment and 3-d systemic treatment, 3-d intramammary treatment and culling bacteriologically unrecovered clinical IMI cows, and 5-d intramammary treatment and culling bacteriologically unrecovered clinical IMI cows. Sensitivity analysis was conducted on parameter input values. The results showed that interventions including antibiotic treatment combined with culling unrecovered clinical IMI cows resulted in the lowest transmission, number of IMI cases, and persistent subclinical IMI cases. Nonetheless, the high associated costs of culling bacteriologically unrecovered clinical IMI cows made the other scenarios with a long and intensive antibiotic treatment, but without culling, the most cost effective. The model was sensitive to changes to the cure rate of clinical IMI following treatment, but the ranking of the intervention scenarios did not change. The model was most sensitive to the changes to the transmission rate of Staph. aureus. The ranking of the intervention scenarios changed at low transmission rate of this pathogen, in which the default scenario became the most cost-effective scenario. In case of high transmission of contagious IMI pathogens, long and intensive treatment of clinical IMI should be preceded by strategies that lower the transmission.