Summary Background In 2000, seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the USA and resulted in dramatic reductions in invasive pneumococcal disease (IPD) and moderate ...increases in non-PCV7 type IPD. In 2010, PCV13 replaced PCV7 in the US immunisation schedule. We aimed to assess the effect of use of PCV13 in children on IPD in children and adults in the USA. Methods We used laboratory-based and population-based data on incidence of IPD from the Active Bacterial Core surveillance (part of the Centers for Disease Control and Prevention's Emerging Infections Program) in a time-series model to compare rates of IPD before and after the introduction of PCV13. Cases of IPD between July 1, 2004, and June 30, 2013, were classified as being caused by the PCV13 serotypes against which PCV7 has no effect (PCV13 minus PCV7). In a time-series model, we used an expected outcomes approach to compare the reported incidence of IPD to that which would have been expected if PCV13 had not replaced PCV7. Findings Compared with incidence expected among children younger than 5 years if PCV7 alone had been continued, incidence of IPD overall declined by 64% (95% interval estimate 95% IE 59–68) and IPD caused by PCV13 minus PCV7 serotypes declined by 93% (91–94), by July, 2012, to June, 2013. Among adults, incidence of IPD overall also declined by 12–32% and IPD caused by PCV13 minus PCV7 type IPD declined by 58–72%, depending on age. We estimated that over 30 000 cases of IPD and 3000 deaths were averted in the first 3 years after the introduction of PCV13. Interpretation PCV13 reduced IPD across all age groups when used routinely in children in the USA. These findings provide reassurance that, similar to PCV7, PCVs with additional serotypes can also prevent transmission to unvaccinated populations. Funding Centers for Disease Control and Prevention.
The National Action Plan for Combating Antibiotic-Resistant Bacteria set a goal of reducing inappropriate outpatient antibiotic use by 50% by 2020, but the extent of inappropriate outpatient ...antibiotic use is unknown.
To estimate the rates of outpatient oral antibiotic prescribing by age and diagnosis, and the estimated portions of antibiotic use that may be inappropriate in adults and children in the United States.
Using the 2010-2011 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, annual numbers and population-adjusted rates with 95% confidence intervals of ambulatory visits with oral antibiotic prescriptions by age, region, and diagnosis in the United States were estimated.
Ambulatory care visits.
Based on national guidelines and regional variation in prescribing, diagnosis-specific prevalence and rates of total and appropriate antibiotic prescriptions were determined. These rates were combined to calculate an estimate of the appropriate annual rate of antibiotic prescriptions per 1000 population.
Of the 184,032 sampled visits, 12.6% of visits (95% CI, 12.0%-13.3%) resulted in antibiotic prescriptions. Sinusitis was the single diagnosis associated with the most antibiotic prescriptions per 1000 population (56 antibiotic prescriptions 95% CI, 48-64), followed by suppurative otitis media (47 antibiotic prescriptions 95% CI, 41-54), and pharyngitis (43 antibiotic prescriptions 95% CI, 38-49). Collectively, acute respiratory conditions per 1000 population led to 221 antibiotic prescriptions (95% CI, 198-245) annually, but only 111 antibiotic prescriptions were estimated to be appropriate for these conditions. Per 1000 population, among all conditions and ages combined in 2010-2011, an estimated 506 antibiotic prescriptions (95% CI, 458-554) were written annually, and, of these, 353 antibiotic prescriptions were estimated to be appropriate antibiotic prescriptions.
In the United States in 2010-2011, there was an estimated annual antibiotic prescription rate per 1000 population of 506, but only an estimated 353 antibiotic prescriptions were likely appropriate, supporting the need for establishing a goal for outpatient antibiotic stewardship.
The study of infectious disease has been aided by model organisms, which have helped to elucidate molecular mechanisms and contributed to the development of new treatments; however, the lack of a ...conceptual framework for unifying findings across models, combined with host variability, has impeded progress and translation. Here, we fill this gap with a simple graphical and mathematical framework to study disease tolerance, the dose response curve relating health to microbe load; this approach helped uncover parameters that were previously overlooked. Using a model experimental system in which we challenged Drosophila melanogaster with the pathogen Listeria monocytogenes, we tested this framework, finding that microbe growth, the immune response, and disease tolerance were all well represented by sigmoid models. As we altered the system by varying host or pathogen genetics, disease tolerance varied, as we would expect if it was indeed governed by parameters controlling the sensitivity of the system (the number of bacteria required to trigger a response) and maximal effect size according to a logistic equation. Though either the pathogen or host immune response or both together could theoretically be the proximal cause of pathology that killed the flies, we found that the pathogen, but not the immune response, drove damage in this model. With this new understanding of the circuitry controlling disease tolerance, we can now propose better ways of choosing, combining, and developing treatments.
Group B Streptococcus (GBS) is an important cause of invasive bacterial disease. Previous studies have shown a substantial and increasing burden of GBS infections among nonpregnant adults, ...particularly older adults and those with underlying medical conditions.
To update trends of invasive GBS disease among US adults using population-based surveillance data.
In this population-based surveillance study, a case was defined as isolation of GBS from a sterile site between January 1, 2008, and December 31, 2016. Demographic and clinical data were abstracted from medical records. Rates were calculated using US Census data. Antimicrobial susceptibility testing and serotyping were performed on a subset of isolates. Case patients were residents of 1 of 10 catchment areas of the Active Bacterial Core surveillance (ABCs) network, representing approximately 11.5% of the US adult population. Patients were included in the study if they were nonpregnant, were 18 years or older, were residents of an ABCs catchment site, and had a positive GBS culture from a normally sterile body site.
Trends in GBS cases overall and by demographic characteristics (sex, age, and race), underlying clinical conditions of patients, and isolate characteristics are described.
The ABCs network detected 21 250 patients with invasive GBS among nonpregnant adults from 2008 through 2016. The GBS incidence in this population increased from 8.1 cases per 100 000 population in 2008 to 10.9 in 2016 (P = .002 for trend). There were 3146 cases reported in 2016 (59% male; median age, 64 years; age range, 18-103 years). The GBS incidence was higher among men than women and among blacks than whites and increased with age. Projected to the US population, an estimated 27 729 cases of invasive disease and 1541 deaths occurred in the United States in 2016. Ninety-five percent of cases in 2016 occurred in someone with at least 1 underlying condition, most commonly obesity (53.9%) and diabetes (53.4%). Resistance to clindamycin increased from 37.0% of isolates in 2011 to 43.2% in 2016 (P = .02). Serotypes Ia, Ib, II, III, and V accounted for 86.4% of isolates in 2016; serotype IV increased from 4.7% in 2008 to 11.3% in 2016 (P < .001 for trend).
The public health burden of invasive GBS disease among nonpregnant adults is substantial and continues to increase. Chronic diseases, such as obesity and diabetes, may contribute.
Invasive disease owing to group B Streptococcus (GBS) remains an important cause of illness and death among infants younger than 90 days in the United States, despite declines in early-onset disease ...(EOD; with onset at 0-6 days of life) that are attributed to intrapartum antibiotic prophylaxis (IAP). Maternal vaccines to prevent infant GBS disease are currently under development.
To describe incidence rates, case characteristics, antimicrobial resistance, and serotype distribution of EOD and late-onset disease (LOD; with onset at 7-89 days of life) in the United States from 2006 to 2015 to inform IAP guidelines and vaccine development.
This study used active population-based and laboratory-based surveillance for invasive GBS disease conducted through Active Bacterial Core surveillance in selected counties of 10 states across the United States. Residents of Active Bacterial Core surveillance areas who were younger than 90 days and had invasive GBS disease in 2006 to 2015 were included. Data were analyzed from December 2017 to April 2018.
Group B Streptococcus isolated from a normally sterile site.
Early-onset disease and LOD incidence rates and associated GBS serotypes and antimicrobial resistance.
The Active Bacterial Core surveillance program identified 1277 cases of EOD and 1387 cases of LOD. From 2006 to 2015, EOD incidence declined significantly from 0.37 to 0.23 per 1000 live births (P < .001), and LOD rates remained stable (mean, 0.31 per 1000 live births). Among the mothers of 1277 infants with EOD, 617 (48.3%) had no indications for IAP and did not receive it, and 278 (21.8%) failed to receive IAP despite having indications. Serotype data were available for 1743 of 1897 patients (91.3%) from 7 sites that collect GBS isolates. Among patients with EOD, serotypes Ia (242 27.3%) and III (242 27.3%) were most common. Among patients with LOD, serotype III was most common (481 56.2%), and this increased from 2006 to 2015 from 0.12 to 0.20 cases per 1000 live births (P < .001). Serotype IV caused 53 cases (6.2%) of EOD and LOD combined. The 6 most common serotypes (Ia, Ib, II, III, IV, and V) caused 881 EOD cases (99.3%) and 853 LOD cases (99.7%). No β-lactam resistance was identified; 359 isolates (20.8%) tested showed constitutive clindamycin resistance. In 2015, an estimated 840 EOD cases and 1265 LOD cases occurred nationally.
The rates of LOD among US infants are now higher than EOD rates. Combined with addressing IAP implementation gaps, an effective vaccine covering the most common serotypes might further reduce EOD rates and help prevent LOD, for which there is no current public health intervention.
Infected hosts differ in their responses to pathogens; some hosts are resilient and recover their original health, whereas others follow a divergent path and die. To quantitate these differences, we ...propose mapping the routes infected individuals take through "disease space." We find that when plotting physiological parameters against each other, many pairs have hysteretic relationships that identify the current location of the host and predict the future route of the infection. These maps can readily be constructed from experimental longitudinal data, and we provide two methods to generate the maps from the cross-sectional data that is commonly gathered in field trials. We hypothesize that resilient hosts tend to take small loops through disease space, whereas nonresilient individuals take large loops. We support this hypothesis with experimental data in mice infected with Plasmodium chabaudi, finding that dying mice trace a large arc in red blood cells (RBCs) by reticulocyte space as compared to surviving mice. We find that human malaria patients who are heterozygous for sickle cell hemoglobin occupy a small area of RBCs by reticulocyte space, suggesting this approach can be used to distinguish resilience in human populations. This technique should be broadly useful in describing the in-host dynamics of infections in both model hosts and patients at both population and individual levels.
The availability of high-dose (HD) influenza vaccine for seniors should decrease influenza-related hospitalization. Studies to date show a range of mostly moderate increased HD vaccine effectiveness ...(VE). While a ‘healthy vaccinee’ phenomenon can inflate VE, for influenza and particularly an HD vaccine targeted at frailer adults, an ‘at-risk vaccinee’ bias may deflate VE estimates. We assessed senior HD vaccine effectiveness against influenza-related hospitalization by linking immunization registry records to hospitalizations. We also examined whether adding strata typically ignored in case-control matching schemas, such as residence areas, exact age, and provider biases, would increase VE.
For the 2016–17 influenza season in the Portland metropolitan area, the differential VE for the HD vaccine in preventing PCR-confirmed influenza hospitalization was assessed by a nested series of models across matching strata. For an exact match for high-dose and standard-dose seniors, matching elements included exact age, gender, residence type, race-ethnicity, provider bias, and residence area (zipcode).
As a first step, a simple aggregate comparison of influenza-related hospitalization risk showed no added HD effectiveness. For the nested models, adding strata increased VE. In the final model, among 23,712 matched pairs of HD to SD vaccinated seniors, the HD vaccine was 30.7% (95%CI: 8–48%) more effective in preventing influenza-related hospitalization.
For this study, the high-dose influenza vaccine provided superior protection for seniors against influenza hospitalization. Including matching elements as exact year of age and residence zipcode all added to the calculation of VE. As a warning, non-matched or overly simple matched VE study designs may substantially under-estimate VE.
Purpose
To assess the importance of each blastocyst morphological criteria with pregnancy and perinatal outcomes.
Methods
This single-center retrospective cohort study included blastocyst single ...embryo transfers (SET) performed between 1/2012–2/2018. Poisson regression was used to evaluate pregnancy outcomes following fresh and cryopreserved embryo transfer (CET) for association with blastocyst expansion, inner cell mass (ICM) quality, and trophectoderm (TE) quality. Among cycles resulting in live birth, associations with preterm birth, small for gestational age (SGA) and large for gestational age (LGA), were evaluated using logistic regression.
Results
A total of 1023 fresh and 1222 CET cycles were included, of which 465 (45.1%) fresh and 600 (48.5%) CET cycles resulted in singleton live birth. Clinical pregnancy rates increased with increasing expansion among fresh transfers (
p
for trend = 0.001) but not CET (
p
= 0.221), and with TE quality for both fresh and CET cycles (
p
= 0.005 and < 0.0001, respectively). Live birth rates increased with increasing expansion (fresh
p
= 0.005, CET
p
=
0
.018) and TE quality (fresh
p
= 0.028, CET
p
= 0.023). ICM grade was not associated with pregnancy outcomes; however, higher ICM quality among CET cycles was associated with increased chance of preterm birth (
p =
0.005).
Conclusions
In blastocyst SET, blastocyst expansion and TE quality were each associated with clinical pregnancy and live birth. While higher ICM quality was associated with increased chance of preterm birth among CET, no other associations with perinatal outcomes were identified. Clinicians can be reassured that pregnancies from blastocysts with lower expansion, ICM, or TE qualities are not more likely to result in adverse perinatal outcomes.
BackgroundSerotype 19A invasive pneumococcal disease (IPD) increased annually in the United States after the introduction of the 7-valent conjugate vaccine (PCV7). To understand this increase, we ...characterized serotype 19A isolates recovered during 2005 MethodsIPD cases during 1998–2005 were identified through population-based surveillance. We performed susceptibility testing and multilocus sequence typing on 528 (95%) of 554 serotype 19A isolates reported in 2005 ResultsThe incidence of IPD due to serotype 19A increased from 0.8 to 2.5 cases per 100,000 population between 1998 and 2005 (P<.05), whereas the overall incidence of IPD decreased from 24.4 to 13.8 cases per 100,000 population (P<.05). Simultaneously, the incidence of IPD due to penicillin-resistant 19A isolates increased from 6.7% to 35% (P<.0001). Of 151 penicillin-resistant 19A isolates, 111 (73.5%) belonged to the rapidly emerging clonal complex 320, which is related to multidrug-resistant Taiwan19F-14. The remaining penicillin-resistant strains were highly related to other clones of PCV7 serotypes or to isolates within major 19A clonal complex 199 (CC199). In 1999, only CC199 and 3 minor clones were apparent among serotype 19A isolates. During 2005, 11 multiple-isolate clonal sets were detected, including capsular switch variants of a serotype 4 clone ConclusionsPCV7 ineffectiveness against serotype 19A, antibiotic resistance, clonal expansion and emergence, and capsular switching have contributed to the genetic diversity of 19A and to its emergence as the predominant invasive pneumococcal serotype in the United States
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