The need for a method to examine complex, multidisciplinary processes involving many diverse organizations initially led multiple US federal agencies to adopt the traditional Kaizen, a Lean process improvement method typically used within a single organization, to encompass multiple organizations each with its own leadership and priorities. First, the Centers for Medicare and Medicaid Services and the Office of the National Coordinator for Health Information Technology adapted Kaizen to federal agency processes for the development of electronic clinical quality measures. Later, the Centers for Disease Control and Prevention (CDC) further modified this adapted Kaizen during its Adapting Clinical Guidelines for the Digital Age (ACG) initiative, which aimed to improve the broader scope of guideline development and implementation. This is a methods article to document the adapted Kaizen method for future use in similar complex processes, illustrating how to apply the adapted Kaizen through CDC's ACG initiative and showing the reach achieved by using the adapted Kaizen method. The adapted Kaizen includes pre-Kaizen planning, a Kaizen event, and post-Kaizen implementation that accommodate multidisciplinary and multi-organizational participation. ACG included 5 workgroups that each developed products to support their respective scope: Guideline Creation, Informatics Framework, Translation and Implementation, Communication and Dissemination, and Evaluation. Despite challenges gathering diverse perspectives and balancing the competing priorities of multiple organizations, the ACG participants produced interrelated standards, processes, and tools-further described in separate publications-that programs and partners have leveraged. Use of a siloed approach may not have supported the development and dissemination of these products.

BACKGROUND: The incidence of invasive disease caused by group A streptococcus (GAS) has increased in multiple countries in the past 15 years. However, despite these reports, to the best of our knowledge, no systematic reviews and combined estimates of the incidence of invasive GAS have been done in key high-risk groups. To address this, we estimated the incidence of invasive GAS disease, including death and disability outcomes, among two high-risk groups-namely, pregnant women and children younger than 5 years. METHODS: We did a systematic review and meta-analyses on invasive GAS outcomes, including incidence, case fatality risks, and neurodevelopmental impairment risk, among pregnant women, neonates (younger than 28 days), infants (younger than 1 year), and children (younger than 5 years) worldwide and by income region. We searched several databases for articles published from Jan 1, 2000, to June 3, 2020, for publications that reported invasive GAS outcomes, and we sought unpublished data from an investigator group of collaborators. We included studies with data on invasive GAS cases, defined as laboratory isolation of Streptococcus pyogenes from any normally sterile site, or isolation of S pyogenes from a non-sterile site in a patient with necrotising fasciitis or streptococcal toxic shock syndrome. For inclusion in pooled incidence estimates, studies had to report a population denominator, and for inclusion in pooled estimates of case fatality risk, studies had to report aggregate data on the outcome of interest and the total number of cases included as a denominator. We excluded studies focusing on groups at very high risk (eg, only preterm infants). We assessed heterogeneity with I(2). FINDINGS: Of the 950 published articles and 29 unpublished datasets identified, 20 studies (seven unpublished; 3829 cases of invasive GAS) from 12 countries provided sufficient data to be included in pooled estimates of outcomes. We did not identify studies reporting invasive GAS incidence among pregnant women in low-income and middle-income countries (LMICs) nor any reporting neurodevelopmental impairment after invasive GAS in LMICs. In nine studies from high-income countries (HICs) that reported invasive GAS in pregnancy and the post-partum period, invasive GAS incidence was 0·12 per 1000 livebirths (95% CI 0·11 to 0·14; I(2)=100%). Invasive GAS incidence was 0·04 per 1000 livebirths (0·03 to 0·05; I(2)=100%; 11 studies) for neonates, 0·13 per 1000 livebirths (0·10 to 0·16; I(2)=100%; ten studies) for infants, and 0·09 per 1000 person-years (95% CI 0·07 to 0·10; I(2)=100%; nine studies) for children worldwide; 0·12 per 1000 livebirths (95% CI 0·00 to 0·24; I(2)=100%; three studies) in neonates, 0·33 per 1000 livebirths (-0·22 to 0·88; I(2)=100%; two studies) in infants, and 0·22 per 1000 person-years (0·13 to 0·31; I(2)=100%; two studies) in children in LMICs; and 0·02 per 1000 livebirths (0·00 to 0·03; I(2)=100%; eight studies) in neonates, 0·08 per 1000 livebirths (0·05 to 0·11; I(2)=100%; eight studies) in infants, and 0·05 per 1000 person-years (0·03 to 0·06; I(2)=100%; seven studies) in children for HICs. Case fatality risks were high, particularly among neonates in LMICs (61% [95% CI 33 to 89]; I(2)=54%; two studies). INTERPRETATION: We found a substantial burden of invasive GAS among young children. In LMICs, little data were available for neonates and children and no data were available for pregnant women. Incidences of invasive GAS are likely to be underestimates, particularly in LMICs, due to low GAS surveillance. It is essential to improve available data to inform development of prevention and management strategies for invasive GAS. FUNDING: Wellcome Trust.

The effect of second generation pneumococcal conjugate vaccines on invasive pneumococcal disease (IPD) strain distributions have not yet been well described. We analyzed IPD isolates recovered from children <5 years of age through Active Bacterial Core surveillance before (2008-2009; n=828) and after (2011-2013; n=600) 13-valent vaccine (PCV13) implementation. We employed conventional testing, PCR/electrospray ionization mass spectrometry, and whole genome sequence (WGS) analysis to identify serotypes, resistance features, genotypes, and pilus types. PCV13, licensed in February of 2010, effectively targeted all major 19A and 7F genotypes and decreased antimicrobial resistance primarily due to removal of the 19A/ST320 complex. The strain complex contributing most to remaining beta-lactam resistance during 2011-2013 was 35B/ST558. Significant emergence of non-vaccine clonal complexes was not evident. Due to the removal of vaccine serotype strains, positivity for one or both pilus types (PI-1 and PI-2) decreased in the post PCV13 years 2011-2013 relative to 2008-2009 (decreases of 32-55% for PI-1, > 95% for PI-2 and combined PI-1 + PI-2). beta-lactam susceptibility phenotypes correlated consistently with transpeptidase region sequence combinations of the three major penicillin binding proteins (PBPs) determined through WGS. Other major resistance features were predictable by DNA signatures from WGS. Multilocus sequence data combined with PBP combinations identified progeny, serotype donors, and recipient strains in serotype switch events. PCV13 decreased all PCV13 serotype clones and concurrently decreased strain subsets with resistance and/or adherence features conducive for successful carriage. Our results serve as a reference describing key features of current pediatric IPD strains in the United States after PCV13 implementation.

BACKGROUND: Streptococcus pneumoniae (SP) serotype distribution among nasopharyngeal (NP) carriage isolates changed significantly after the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7). We evaluated the impact on NP carriage and invasive disease of SP after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in March 2010. METHODS: NP swabs were collected from children 6-59 months of age in an emergency department from July 2010-June 2013. After broth enrichment, samples were cultured for SP and isolates were serotyped. Clinical and immunization records were reviewed. Findings during six sequential 6-month study periods were compared. Surveillance isolates of invasive disease isolates were reviewed. RESULTS: A total of 2,048 children were enrolled and 656 (32%) were SP carriers. Mean age of carriers was 27 months, 54% were males. Carriage was higher among daycare attendees (p<0.01) and children with respiratory tract illnesses (p<0.5) and otitis media (p<0.01). Commonly carried serotypes included 35B (15.2%), 15B/C (14.2%), 19A (9.6%), 11A (8%), 23B (5.6%), 6C (5.3%), 21 (5%), and 15A (5%); 13.9% were PCV13 serotypes. The proportion of children with SP carriage remained stable but the serotype distribution changed over the study period. Among carriers, PCV13 serotypes declined from 29% (36/124) to 3% (3/99) (p<0.0001), predominantly due to decline of serotype 19A from 25.8% (32/124) to 3% (3/99) (p<0.0001); non-PCV13 serotypes (excluding 6C) increased from 68.4% (78/114) to 97% (95/98) (p<0.0001); serotype 35B significantly increased from 8.9% (11/124) to 25.3% (25/99) (p<0.05). Nonsusceptibility to ceftriaxone declined from 22.6% (28/124) to 0% (0/99) (p<0.0001), with a similar decline in penicillin nonsusceptibility. CONCLUSIONS: Introduction of PCV13 for universal infant use was associated with significant reductions in nasopharyngeal carriage of PCV13 serotypes and resistant strains. Carriage of non-PCV13 serotypes increased modestly, particularly serotype 35B. Further investigation is warranted to determine whether non-vaccine pneumococcal serotypes carried in the nasopharynx are associated with significant replacement disease.

A fatal case of melioidosis was diagnosed in Ohio one month after culture results were initially reported as a Bacillus species. To identify a source of infection and assess risk in patient contacts, we abstracted patient charts; interviewed physicians and contacts; genetically characterized the isolate; performed a Burkholderia pseudomallei antibody indirect hemagglutination assay on household contacts and pets to assess seropositivity; and collected household plant, soil, liquid, and insect samples for culturing and real-time polymerase chain reaction testing. Family members and pets tested were seronegative for B. pseudomallei. Environmental samples were negative by real-time polymerase chain reaction and culture. Although the patient never traveled internationally, the isolate genotype was consistent with an isolated that originated in Southeast Asia. This investigation identified the fifth reported locally acquired non-laboratory melioidosis case in the contiguous United States. Physicians and laboratories should be aware of this potentially emerging disease and refer positive cultures to a Laboratory Response Network laboratory.

Since nasopharyngeal carriage of pneumococcus precedes invasive pneumococcal disease, characteristics of carriage isolates could be incorrectly assumed to reflect those of invasive isolates. While most pneumococci express a capsular polysaccharide, nontypeable pneumococci are sometimes isolated. Carriage nontypeables tend to encode novel surface proteins in place of a capsular polysaccharide synthetic locus, the cps locus. In contrast, capsular polysaccharide is believed to be indispensable for invasive pneumococcal disease, and nontypeables from population-based invasive pneumococcal disease surveillance have not been extensively characterized. We received 14,328 invasive pneumococcal isolates through the Active Bacterial Core surveillance program during 2006-2009. Isolates that were nontypeable by Quellung serotyping were characterized by PCR serotyping, sequence analyses of the cps locus, and multilocus sequence typing. Eighty-eight isolates were Quellung-nontypeable (0.61%). Of these, 79 (89.8%) contained cps loci. Twenty-two nontypeables exhibited serotype 8 cps loci with defects, primarily within wchA. Six of the remaining nine isolates contained previously-described aliB homologs in place of cps loci. Multilocus sequence typing revealed that most nontypeables that lacked capsular biosynthetic genes were related to established non-encapsulated lineages. Thus, invasive pneumococcal disease caused by nontypeable pneumococcus remains rare in the United States, and while carriage nontypeables lacking cps loci are frequently isolated, such nontypeable are extremely rare in invasive pneumococcal disease. Most invasive nontypeable pneumococci possess defective cps locus genes, with an over-representation of defective serotype 8 cps variants.

BACKGROUND: Streptococcus pneumoniae is a significant pathogen capable of expressing protective and antigenically diverse capsules. To better understand the molecular basis of capsular antigenic diversity, we investigated the hypothetical serological role of wcjE, which encodes a capsule O-acetyltransferase, in the vaccine-targeted serotype 9V and related serotype 9A. METHODS: We inactivated wcjE by recombination in a serotype 9V strain and determined wcjE sequences of 11 serotype 9A clinical isolates. We determined the antigenic phenotypes of these pneumococcal strains with serogroup 9-specific antibodies and flow cytometry. RESULTS: Inactivation of wcjE in a serotype 9V strain resulted in expression of the 9A phenotype. Each serotype 9A clinical isolate contained a distinct mutation to wcjE. Flow cytometry showed that some 9A isolates (herein named 9Aalpha) expressed trace amounts of 9V-specific epitopes whereas others (named 9Abeta) did not express any. Recombination with 9Aalpha wcjE alleles into a 9Abeta strain conferred partial expression of 9V-specific epitopes. CONCLUSIONS: Each serotype 9A strain independently arose from a serotype 9V strain. Furthermore, clinical isolates identified as 9A can contain mutations to wcjE that are either partially functional or completely nonfunctional, demonstrating a previously unidentified antigenic heterogeneity of serotype 9A isolates.