Tularemia is a rare nationally notifiable zoonosis, caused by the tier-1 select agent Francisella tularensis, that has been reported from all U.S. states except Hawaii. Clinical manifestations typically include fever and localized symptoms that vary by route of infection. The case fatality rate of tularemia is typically <2% but can be higher depending on clinical manifestation and infecting strain. Tularemia is treatable with antibiotics. During 2011-2022, a total of 47 states reported 2,462 tularemia cases, but four central states (Arkansas, Kansas, Missouri, and Oklahoma) accounted for 50% of all reported cases. Incidence was highest among children aged 5-9 years (0.083 per 100,000 population) and adult males aged 65-84 years (range = 0.133-0.161). Incidence among American Indian or Alaska Native persons (0.260) was approximately five times that among White persons (0.057). The average annual incidence of tularemia in the United States during 2011-2022 (0.064) was 56% higher than that reported during 2001-2010 (0.041), largely resulting from increased reporting of probable cases. These findings might reflect an actual increase in human infection or improved case detection amid changes in commercially available laboratory tests during this period. Reducing tularemia incidence will require tailored prevention education; mitigating morbidity and mortality will require health care provider education, particularly among providers serving tribal populations, regarding early and accurate diagnosis and treatment.

Tick-borne diseases are commonly reported in the United States, but frequency of tick bites and care-seeking behaviors following tick bites are poorly understood. We used nationally representative survey data to describe the frequency of tick bites among people living in the United States and how often, where, and why care-seeking associated with tick bites occurs. We found that over 31 million people (nearly 1 in 10) living in the United States might experience a tick bite each year and highlight regional trends in associated care-seeking behaviors. These findings emphasize the need for effective tick bite prevention education and regionally tailored healthcare provider recommendations for management of tick-borne diseases.

BACKGROUND: Commercial insurance claims data are a stable and consistent source of information on Lyme disease diagnoses in the United States and can contribute to our understanding of overall disease burden and the tracking of epidemiological trends. Algorithms consisting of diagnosis codes and antimicrobial treatment information have been used to identify Lyme disease diagnoses in claims data, but there might be opportunity to improve their accuracy. METHODS: We developed three modified versions of our existing claims-based Lyme disease algorithm; each reflected refined criteria regarding antimicrobials prescribed and/or maximum days between diagnosis code and qualifying prescription claim. We applied each to a large national commercial claims database to identify Lyme disease diagnoses during 2016-2019. We then compared characteristics of Lyme disease diagnoses identified by each of the modified algorithms to those identified by our original algorithm to assess differences from expected trends in demographics, seasonality, and geography. RESULTS: Observed differences in characteristics of patients with diagnoses identified by the three modified algorithms and our original algorithm were minimal, and differences in age and sex, in particular, were small enough that they could have been due to chance. However, one modified algorithm resulted in proportionally more diagnoses in men, during peak summer months, and in high-incidence jurisdictions, more closely reflecting epidemiological trends documented through public health surveillance. This algorithm limited treatment to only first-line recommended antimicrobials and shortened the timeframe between a Lyme disease diagnosis code and qualifying prescription claim. CONCLUSIONS: As compared to our original algorithm, a modified algorithm that limits the antimicrobials prescribed and shortens the timeframe between a diagnosis code and a qualifying prescription claim might more accurately identify Lyme disease diagnoses when utilizing insurance claims data for supplementary, routine identification and monitoring of Lyme disease diagnoses.

AIMS AND METHODS: In the United States, blacklegged Ixodes spp. ticks are the primary vector of Lyme disease. Minnesota is among the states with the highest reported incidence of Lyme disease, having an average of 1857 cases reported annually during 2011-2019. In contrast to the Northeast and mid-Atlantic United States where exposure to ticks predominately occurs around the home, the circumstances regarding risk for exposure to blacklegged ticks in Minnesota are not well understood, and risk is thought to be highest in rural areas where people often participate in recreational activities (e.g. hiking, visiting cabins). We analysed enhanced surveillance data collected by the Minnesota Department of Health during 2011-2019 to describe epidemiologic and tick exposure characteristics among people with reported Lyme disease. RESULTS: We found that younger age, male gender, residence in a county with lower Lyme disease risk, residence in the Minneapolis-St. Paul metropolitan area, and an illness onset date later in the year were independently associated with higher odds of reporting tick exposures away from the home. We also describe the range of activities associated with tick exposure away from the home, including both recreational and occupational activities. CONCLUSIONS: These findings refine our understanding of Lyme disease risk in Minnesota and highlight the need for heterogeneous public health prevention messaging, including an increased focus on peridomestic prevention measures among older individuals living in high-risk rural areas and recreational and occupational prevention measures among younger individuals living in the Minneapolis-St. Paul metropolitan area.

Lyme disease, a tickborne zoonosis caused by certain species of Borrelia spirochetes, is the most common vectorborne disease in the United States. Approximately 90% of all cases are reported from 15 high-incidence jurisdictions in the Northeast, mid-Atlantic, and upper-Midwest regions. After the implementation of a revised surveillance case definition in 2022, high-incidence jurisdictions report cases based on laboratory evidence alone, without need for additional clinical information. In 2022, 62,551 Lyme disease cases were reported to CDC, 1.7 times the annual average of 37,118 cases reported during 2017-2019. Annual incidence increased most in older age groups, with incidence among adults aged ≥65 years approximately double that during 2017-2019. The sharp increase in reported Lyme disease cases in 2022 likely reflects changes in surveillance methods rather than change in disease risk. Although these changes improve standardization of surveillance across jurisdictions, they preclude detailed comparison with historical data.

OBJECTIVE: Clinical practice guidelines are often created through collaboration among organizations. Use of inconsistent terminology may cause poor communication and delays. This study aimed to develop a glossary of terms related to collaboration in guideline development. STUDY DESIGN AND SETTING: A literature review of collaborative guidelines was performed to develop an initial list of terms related to guideline collaboration. The list of terms was presented to the members of the Guideline International Network Guidelines Collaboration Working Group, who provided presumptive definitions for each term and proposed additional terms to be included. The revised list was subsequently reviewed by an international, multidisciplinary panel of expert stakeholders. Recommendations received during this pre-Delphi review were implemented to augment an initial draft glossary. The glossary was then critically evaluated and refined through two rounds of Delphi surveys and a virtual consensus meeting with all panel members as Delphi participants. RESULTS: Forty-nine experts participated in the pre-Delphi survey and 44 participated in the two-round Delphi process. Consensus was reached for 37 terms and definitions. CONCLUSION: Uptake and utilization of this guideline collaboration glossary by key organizations and stakeholder groups may facilitate collaboration among guideline-producing organizations by improving communication, minimizing conflicts, and increasing guideline development efficiency.

Description: The Kidney Disease: Improving Global Outcomes (KDIGO) 2018 clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in chronic kidney disease (CKD) is an extensive update of KDIGO's 2008 guideline on HCV infection in CKD. This update reflects the major advances since the introduction of direct-acting antivirals (DAAs) in the management of HCV infection in the CKD population. Methods: The KDIGO work group tasked with developing the HCV and CKD guideline defined the scope of the guideline, gathered evidence, determined topics for systematic review, and graded the quality of evidence previously summarized by the evidence review team. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to appraise the quality of evidence and rate the strength of the recommendations. Searches of the English-language literature were conducted through May 2017 and were supplemented with targeted searches for studies of DAA treatment and with abstracts from nephrology, hepatology, and transplantation conferences. A review process involving many stakeholders, subject matter experts, and industry and national organizations informed the guideline's final modification. Recommendation: The updated guideline comprises 66 recommendations. This synopsis focuses on 32 key recommendations pertinent to the prevention, diagnosis, treatment, and management of HCV infection in adult CKD populations.

Infection with the hepatitis C virus (HCV) has adverse liver, kidney, and cardiovascular consequences in patients with chronic kidney disease (CKD), including those on dialysis therapy and in those with a kidney transplant. Since the publication of the original Kidney Disease: Improving Global Outcomes (KDIGO) HCV Guideline in 2008, major advances in HCV management, particularly with the advent of direct-acting antiviral therapies, have now made the cure of HCV possible in CKD patients. In addition, diagnostic techniques have evolved to enable the noninvasive diagnosis of liver fibrosis. Therefore, the Work Group undertook a comprehensive review and update of the KDIGO HCV in CKD Guideline. This Executive Summary highlights key aspects of the guideline recommendations.

BACKGROUND: Proficiency testing (PT) can have regulatory and nonregulatory uses, providing an effective tool for quality improvement. Clinical laboratories were surveyed to determine how they perceive PT and how they use PT results and materials to improve laboratory testing quality. METHODS: All laboratories certified to perform nonwaived testing under the CLIA regulations expected to perform required PT were invited to participate in the survey. We examined respondents' use of PT from 5 laboratory types: hospital, independent, public health, physician office, and "all other." Respondents' awareness of resources about PT was also examined. Several questions allowed responses on a categorical scale. RESULTS: Varying proportions of the respondents (n = 769) used PT to identify problems in the preanalytic (48%), analytic (86%), and postanalytic (76%) phases of testing. Responses also showed that PT was important for demonstrating personnel competency (93%), inappropriate specimen handling (80%), incorrect result interpretation (84%), and other uses. Respodents purchased PT even when not required to do so (77%). Based on all responses, most considered PT worth the cost (65%). CONCLUSIONS: Laboratories, regardless of type, have found ways of using leftover PT samples and the information from PT event summaries to help improve laboratory quality. Our findings suggest many laboratories are not taking full advantage of PT to improve testing quality. Additionally, the study suggests a need to improve awareness of resources about PT.

As an external assessment of quality, proficiency testing (PT) is recognized as one essential component for assuring quality testing in clinical laboratories.1–3 Each laboratory that performs non-waived testing is required by the Clinical Laboratory Improvement Amendments of 1988 (CLIA) to perform PT. The CLIA regulations specify requirements for PT program provider approval by the Department of Health and Human Services (HHS). | | The CLIA law changed the paradigm for providers from an educational to a more regulatory role. Consequently, there are often misperceptions about providers’ operations and their limitations. This report presents some of the common viewpoints held by clinical laboratory professionals and the corresponding perspectives shared by some PT providers. The report is intended to assist clinical laboratories in understanding the constraints faced by PT program providers, learning about potentially helpful provider services, communicating with their providers, and making knowledgeable inquiries as they search for PT services. | | In 2012, the Centers for Disease Control and Prevention (CDC), working in collaboration with the Association of Public Health Laboratories, conducted a series of focus groups that included clinical and public health laboratory professionals to explore how they use and perceive PT.4–5 Some discussions concerned participants’ satisfaction with PT provider services. Participants spoke of issues they had experienced and made recommendations for providers to consider. As a follow-up to the focus groups, in 2015 CDC developed several open-ended questions about some of these issues and sent them to all 11 HHS-approved PT program providers that provide, at a minimum, chemistry analytes. Seven providers furnished either written or verbal answers, which are summarized in this article. Respondents included providers which offer a wide range of programs: programs affiliated with accreditation organizations; those that offer a small number of programs to specific types of laboratories (e.g. physician office laboratories); and some independent and state-affiliated programs.

BACKGROUND: During an October 2005 algal bloom (i.e., a rapid increase or accumulation in the population of algae) off the coast of Nicaragua, 45 people developed symptoms of paralytic shellfish poisoning (PSP) and one person died. PSP in humans is caused by ingestion of saxitoxin, which is a neurotoxin often associated with shellfish contaminated by algal blooms. To explore the relationship between the algal bloom and human illnesses, we performed a case-control study of residents living in a coastal island. We administered a standardized clinical questionnaire, sampled locally harvested seafood and algae, and obtained urine samples for saxitoxin testing from symptomatic and asymptomatic persons. PSP case-patients were defined as island residents who developed at least one neurological symptom during the November 4-16 intoxication period. Seafood and algal samples were analyzed for saxitoxins using the receptor-binding assay and high-performance liquid chromatography. Two urine samples were analyzed for saxitoxins using a newly developed immunoassay. FINDINGS: Three shellfish and two algal samples tested positive for saxitoxins. Ten (9%) of 107 participants developed neurological symptoms during the specified time period and five required hospitalization. While 6 (67%) of 9 possible case-patients and 21 (21%) of 98 controls had eaten fish (p=0.008), all case-patients and 17 (17%) of controls had eaten clams (P<0.0001). The saxitoxin concentration in the urine of a hospitalized case-patient was 21 ng saxitoxin/g creatinine compared to 0.16 ng saxitoxin/g creatinine in the single control patient's urine. CONCLUSIONS: These findings suggest that a bloom of saxitoxin-producing algae resulted in saxitoxin accumulation in local clams and was responsible for the PSP intoxication.

PURPOSE: Many regions have implemented newborn screening (NBS) for cystic fibrosis (CF) using a limited panel of cystic fibrosis transmembrane regulator (CFTR) mutations after immunoreactive trypsinogen (IRT) analysis. We sought to assess the feasibility of further improving the screening using next-generation sequencing (NGS) technology. METHODS: An NGS assay was used to detect 162 CFTR mutations/variants characterized by the CFTR2 project. We used 67 dried blood spots (DBSs) containing 48 distinct CFTR mutations to validate the assay. NGS assay was retrospectively performed on 165 CF screen-positive samples with one CFTR mutation. RESULTS: The NGS assay was successfully performed using DNA isolated from DBSs, and it correctly detected all CFTR mutations in the validation. Among 165 screen-positive infants with one CFTR mutation, no additional disease-causing mutation was identified in 151 samples consistent with normal sweat tests. Five infants had a CF-causing mutation that was not included in this panel, and nine with two CF-causing mutations were identified. CONCLUSION: The NGS assay was 100% concordant with traditional methods. Retrospective analysis results indicate an IRT/NGS screening algorithm would enable high sensitivity, better specificity and positive predictive value (PPV). This study lays the foundation for prospective studies and for introducing NGS in NBS laboratories.

Although inherited blood disorders are common among children in many parts of Africa, limited data are available about their prevalence or contribution to childhood anaemia. We conducted a cross-sectional survey of 858 children aged 6-35 months who were randomly selected from 60 villages in western Kenya. Haemoglobin (Hb), ferritin, malaria, C-reactive protein (CRP) and retinol binding protein (RBP) were measured from capillary blood. Using polymerase chain reaction (PCR), Hb type, -3.7 kb alpha-globin chain deletion, glucose-6-phosphate dehydrogenase (G6PD) genotype and haptoglobin (Hp) genotype were determined. More than 2 out of 3 children had at least one measured blood disorder. Sickle cell trait (HbAS) and disease (HbSS) were found in 17.1% and 1.6% of children, respectively; 38.5% were heterozygotes and 9.6% were homozygotes for alpha(+) -thalassaemia. The Hp 2-2 genotype was found in 20.4% of children, whereas 8.2% of males and 6.8% of children overall had G6PD deficiency. There were no significant differences in the distribution of malaria by the measured blood disorders, except among males with G6PD deficiency who had a lower prevalence of clinical malaria than males of normal G6PD genotype (P = 0.005). After excluding children with malaria parasitaemia, inflammation (CRP > 5 mg L(-1) ), iron deficiency (ferritin < 12 mcg L(-1) ) or vitamin A deficiency (RBP < 0.7 mcg L(-1) ), the prevalence of anaemia among those without alpha(+) -thalassaemia (43.0%) remained significantly lower than that among children who were either heterozygotes (53.5%) or homozygotes (67.7%, P = 0.03). Inherited blood disorders are common among pre-school children in western Kenya and are important contributors to anaemia.

Most newborn screening (NBS) laboratories use second-tier molecular tests for cystic fibrosis (CF) using dried blood spots (DBS). The Centers for Disease Control and Prevention's NBS Quality Assurance Program offers proficiency testing (PT) in DBS for CF transmembrane conductance regulator (CFTR) gene mutation detection. Extensive molecular characterization on 76 CF patients, family members or screen positive newborns was performed for quality assurance. The coding, regulatory regions and portions of all introns were sequenced and large insertions/deletions were characterized as well as two intronic di-nucleotide microsatellites. For CF patient samples, at least two mutations were identified/verified and four specimens contained three likely CF-associated mutations. Thirty-four sequence variations in 152 chromosomes were identified, five of which were not previously reported. Twenty-seven of these variants were used to predict haplotypes from the major haplotype block defined by HapMap data that spans the promoter through intron 19. Chromosomes containing the F508del (p.Phe508del), G542X (p.Gly542X) and N1303K (p.Asn1303Lys) mutations shared a common haplotype subgroup, consistent with a common ancient European founder. Understanding the haplotype background of CF-associated mutations in the U.S. population provides a framework for future phenotype/genotype studies and will assist in determining a likely cis/trans phase of the mutations without need for parent studies.

BACKGROUND: CDC's Newborn Screening Quality Assurance Program collaborated with several U.S. Cystic Fibrosis Care Centers to collect specimens for development of a molecular CFTR proficiency testing program using dried-blood spots for newborn screening laboratories. METHODS: Adult and adolescent patients or carriers donated whole blood that was aliquoted onto filter paper cards. Five blind-coded specimens were sent to participating newborn screening laboratories quarterly. Proficiency testing results were evaluated based on presumptive clinical assessment. Individual evaluations and summary reports were sent to each participating laboratory and technical consultations were offered if incorrect assessments were reported. RESULTS: The current CDC repository contains specimens with 39 different CFTR mutations. Up to 45 laboratories have participated in the program. Three years of data showed that correct assessments were reported 97.7% of the time overall when both mutations could be determined. Incorrect assessments that could have lead to a missed case occurred 0.9% of the time, and no information was reported 1.1% of the time due to sample failure. CONCLUSIONS: Results show that laboratories using molecular assays to detect CFTR mutations are performing satisfactorily. The programmatic results presented demonstrate the importance and complexity of providing proficiency testing for DNA-based assays.