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BACKGROUND: This study characterizes the clinical utility and validity of the Karius test (KT), a plasma microbial cell-free DNA sequencing platform, as an infection surveillance tool among hematopoietic stem cell transplant (HCT) recipients, including monitoring for cytomegalovirus (CMV) and detecting infections relative to standard microbiologic testing (SMT). METHODS: A prospective, observational cohort study was performed among adult HCT recipients as inpatients and outpatients. Serial KTs were performed starting with 1 sample within 14 days before HCT, then weekly from 7-63 days posttransplant then monthly from 3-12 months post-HCT. Diagnostic performance of KT versus CMV polymerase chain reaction was evaluated with positive percent agreement and negative percent agreement. Infectious events (

BACKGROUND: Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield in immunocompromised patients with pneumonia. METHODS: In this prospective, multicenter, observational study of immunocompromised adults undergoing bronchoscopy to establish a pneumonia etiology, plasma microbial cell-free DNA sequencing was compared to standardized usual care testing. Pneumonia etiology was adjudicated by a blinded independent committee. The primary outcome, additive diagnostic value, was assessed in the Per Protocol population (patients with complete testing results and no major protocol deviations) and defined as the percent of patients with an etiology of pneumonia exclusively identified by plasma microbial cell-free DNA sequencing. Clinical additive diagnostic value was assessed in the Per Protocol subgroup with negative usual care testing. RESULTS: Of 257 patients, 173 met Per Protocol criteria. A pneumonia etiology was identified by usual care in 52/173 (30.1%), plasma microbial cell-free DNA sequencing in 49/173 (28.3%) and the combination of both in 73/173 (42.2%) patients. Plasma microbial cell-free DNA sequencing exclusively identified an etiology of pneumonia in 21/173 patients (additive diagnostic value 12.1%, 95% confidence interval [CI], 7.7% to 18.0%, P < .001). In the Per Protocol subgroup with negative usual care testing, plasma microbial cell-free DNA sequencing identified a pneumonia etiology in 21/121 patients (clinical additive diagnostic value 17.4%, 95% CI, 11.1% to 25.3%). CONCLUSIONS: Non-invasive plasma microbial cell-free DNA sequencing significantly increased diagnostic yield in immunocompromised patients with pneumonia undergoing bronchoscopy and extensive microbiologic and molecular testing. CLINICAL TRIALS REGISTRATION: NCT04047719.

Reducing premature mortality associated with age-related chronic diseases, such as cancer and cardiovascular disease, is an urgent priority. We report early results using genomics in combination with advanced imaging and other clinical testing to proactively screen for age-related chronic disease risk among adults. We enrolled active, symptom-free adults in a study of screening for age-related chronic diseases associated with premature mortality. In addition to personal and family medical history and other clinical testing, we obtained whole-genome sequencing (WGS), noncontrast whole-body MRI, dual-energy X-ray absorptiometry (DXA), global metabolomics, a new blood test for prediabetes (Quantose IR), echocardiography (ECHO), ECG, and cardiac rhythm monitoring to identify age-related chronic disease risks. Precision medicine screening using WGS and advanced imaging along with other testing among active, symptom-free adults identified a broad set of complementary age-related chronic disease risks associated with premature mortality and strengthened WGS variant interpretation. This and other similarly designed screening approaches anchored by WGS and advanced imaging may have the potential to extend healthy life among active adults through improved prevention and early detection of age-related chronic diseases (and their risk factors) associated with premature mortality.

Adventure travel is becoming more popular, increasing the likelihood of contact with unusual pathogens. We investigated an outbreak of leptospirosis in "Eco-Challenge" multisport race athletes to determine illness etiology and [...]

An outbreak of serogroup W-135 meningococcal disease occurred during the 2000 Hajj in Saudi Arabia. Disease was reported worldwide in Hajj pilgrims and their close contacts; however, most cases were [...]

We examined outbreak investigations conducted around the world from 1988 to 1999 by the Centers for Disease Control and Prevention's Epidemic Intelligence Service. In 44 (4.0%) of 1,099 investigations, identified [...]

To the Editor: During the 2001 anthrax outbreak, we evaluated and validated a highly sensitive and specific three-target (two plasmid and one chromosomally located target) 5' nuclease assay (real-time polymerase [...]

The bioterrorism-associated human anthrax epidemic in the fall of 2001 highlighted the need for a sensitive, reproducible, and specific laboratory test for the confirmatory diagnosis of human anthrax. The Centers [...]

In October 2001, the first inhalational anthrax case in the United States since 1976 was identified in a media company worker in Florida. A national investigation was initiated to identify [...]

On October 4, 2001, we confirmed the first bioterrorism-related anthrax case identified in the United States in a resident of Palm Beach County, Florida. Epidemiologic investigation indicated that exposure occurred [...]

On Thursday, October 4, 2001, just 24 days after the tragic events of September 11, the Florida Department of Health and the Centers for Disease Control and Prevention (CDC) confirmed [...]

Population-based surveillance for unexplained death and critical illness possibly due to infectious causes (UNEX) was conducted in four U.S. Emerging Infections Program sites (population 7.7 million) from May 1, 1995, [...]

From October 4 to November 2, 2001, the first 10 confirmed cases of inhalational anthrax caused by intentional release of Bacillus anthracis were identified in the United States. Epidemiologic investigation [...]

This article addresses menstrual toxic shock syndrome (TSS) from the context of it being a health threat to women of reproductive age. Results examine national suveillance data on 5,296 cases of TSS with reference to epidemiology, awareness, and monitoring of TSS., Menstrual toxic shock syndrome (TSS) emerged as a public health threat to women of reproductive age in 1979-80. We reviewed surveillance data for the period 1979 to 1996, when 5,296 [...]

Research shows that use of an unapproved adrenal cortex extract (ACE) resulted in the largest outbreak of Mycobacterium abscessus infections during 1995-96 in the United States. Data reveal that 148 persons purchased unapproved ACE in 30 states and 87 suffered postinjection abscesses., An unlicensed injectable medicine sold as adrenal cortex extract (ACE*) and distributed in the alternative medicine community led to the largest outbreak of Mycobacterium abscessus infections reported in the United [...]

Objectives. current knowledge of the epidemiology of cat scratch disease is based primarily on information from case series. We used three national databases to obtain more representative data to determine the incidence and demographics of cat scratch disease. Methods. Records coded with the dignosis of cat scratch disease from two hospital discharge database and an ambulatory care database were analyzed. Costs of diagnostic tests and hospitalization were obtained from a sample of providers and published data. Results. The incidence of patients discharged from hospitals with a diagnosis of cat scratch disease was between 0.77 and 0.86 per 100 000 population per year. Fifty-five percent of the case patients were 18 years of age or younger. Males accounted for 60% of cases. Incidence varied by season; approximately 60% of case patients were discharged in the months September through January. The estimated incidence of disease in ambulatory patients was 9.3 per 100 000 population per year. On the basis of these rates, we estimated the annual health care cost of the disease to be more than $12 million. Conclusions. The rates and seasonality of cat scratch disease found in this study were consistent with previous reports. Adults represented a higher percentage of the total than reported in previous case series, suggesting that the disease may affect more adults than previously recognized. (Am J Public Health. 1993;83:1707-1711), General demographic analysis indicates that cat scratch disease may be more common in adults that previously determined. Cat scratch disease affects the lymph nodes. Records from the Commission on Professional and Hospital Activities (CPHA) and the National Hospital Discharge Survey (NHDS) databases were analysed for the incidence of cat scratch disease. A total of 2,828 records from CPHA and 95 records from NHDS listed such a diagnosis. Children accounted for over half of the cases, with males comprising 60% of the cases. However, adults represented a higher proportion of cases than in previous studies. The rate of incidence was about 0.8 per 100,000 population, a rate similar to earlier epidemiological findings. Researchers estimate that about 22,000 persons are affected each year, with 2,000 people being hospitalized for the disease.

To the Editor: In his letter, Industry-related Outbreak of Human Anthrax, Massachusetts, 1868 (1), Dr. Macher suggests an additional reference to cases of industry-related anthrax that occurred in the United [...]

Abstract Background The World Health Organization (WHO) and partners are collaborating to eradicate poliomyelitis. To monitor progress, countries perform surveillance for acute flaccid paralysis (AFP). The WHO African Regional Office (WHO-AFRO) and the U.S Centers for Disease Control and Prevention are also involved in strengthening infectious disease surveillance and response in Africa. We assessed whether polio-eradication initiative resources are used in the surveillance for and response to other infectious diseases in Africa. Methods During October 1999-March 2000, we developed and administered a survey questionnaire to at least one key informant from the 38 countries that regularly report on polio activities to WHO. The key informants included WHO-AFRO staff assigned to the countries and Ministry of Health personnel. Results We obtained responses from 32 (84%) of the 38 countries. Thirty-one (97%) of the 32 countries had designated surveillance officers for AFP surveillance, and 25 (78%) used the AFP resources for the surveillance and response to other infectious diseases. In 28 (87%) countries, AFP program staff combined detection for AFP and other infectious diseases. Fourteen countries (44%) had used the AFP laboratory specimen transportation system to transport specimens to confirm other infectious disease outbreaks. The majority of the countries that performed AFP surveillance adequately (i.e., non polio AFP rate = 1/100,000 children aged Conclusions Despite concerns regarding the targeted nature of AFP surveillance, it is partially integrated into existing surveillance and response systems in multiple African countries. Resources provided for polio eradication should be used to improve surveillance for and response to other priority infectious diseases in Africa.

Patients with end-stage kidney disease on maintenance hemodialysis commonly develop protein-energy wasting, a syndrome characterized by nutritional and metabolic abnormalities. Nutritional supplementation and exercise are recommended to prevent protein-energy wasting. In a 6-mo prospective randomized, open-label, clinical trial, we reported that the combination of resistance exercise and nutritional supplementation does not have an additive effect on lean body mass measured by dual-energy X-ray absorptiometry. To provide more mechanistic data, we performed a secondary analysis where we hypothesized that the combination of nutritional supplementation and resistance exercise would have additive effects on muscle protein accretion by stable isotope protein kinetic experiments, muscle mass by MRI, and mitochondrial content markers in muscle. We found that 6 mo of nutritional supplementation during hemodialysis increased muscle protein net balance [baseline: 2.5 (-17.8, 13.0) µg·100 mL-1·min-1 vs. 6 mo: 43.7 (13.0, 98.5) µg·100 mL-1·min-1, median (interquartile range), P = 0.04] and mid-thigh fat area [baseline: 162.3 (104.7, 226.6) cm2 vs. 6 mo: 181.9 (126.3, 279.2) cm2, median (interquartile range), P = 0.04]. Three months of nutritional supplementation also increased markers of mitochondrial content in muscle. Although the study is underpowered to detected differences, the combination of nutritional supplementation and exercise failed to show further benefit in protein accretion or muscle cross-sectional area. We conclude that long-term nutritional supplementation increases the skeletal muscle anabolic effect, the fat cross-sectional area of the thigh, and markers of mitochondrial content in skeletal muscle. [ABSTRACT FROM AUTHOR]

Genome sequencing has established clinical utility for rare disease diagnosis. While increasing numbers of individuals have undergone elective genome sequencing, a comprehensive study surveying genome-wide disease-associated genes in adults with deep phenotyping has not been reported. Here we report the results of a 3-y precision medicine study with a goal to integrate wholegenome sequencingwith deep phenotyping. A cohort of 1,190 adult participants (402 female [33.8%]; mean age, 54 y [range 20 to 89+]; 70.6% European) had whole-genome sequencing, and were deeply phenotyped using metabolomics, advanced imaging, and clinical laboratory tests in addition to family/medical history. Of 1,190 adults, 206 (17.3%) had at least 1 genetic variant with pathogenic (P) or likely pathogenic (LP) assessment that suggests a predisposition of genetic risk. A multidisciplinary clinical team reviewed all reportable findings for the assessment of genotype and phenotype associations, and 137 (11.5%) had genotype and phenotype associations. A high percentage of genotype and phenotype associations (>75%) was observed for dyslipidemia (n = 24), cardiomyopathy, arrhythmia, and other cardiac diseases (n = 42), and diabetes and endocrine diseases (n = 17). A lack of genotype and phenotype associations, a potential burden for patient care, was observed in 69 (5.8%) individuals with P/LP variants. Genomics and metabolomics associations identified 61 (5.1%) heterozygotes with phenotype manifestations affecting serum metabolite levels in amino acid, lipid and cofactor, and vitamin pathways. Our descriptive analysis provides results on the integration of whole-genome sequencing and deep phenotyping for clinical assessments in adults. [ABSTRACT FROM AUTHOR]

1. Brief description of the disease Leprosy is a chronic infectious disease caused by Mycobacterium leprae. It usually affects the skin and peripheral nerves but has a wide range of [...]