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Madurella mycetomatis is one of the main causative agents of mycetoma, a debilitating neglected tropical disease. Improved understanding of the genomic diversity of the fungal and bacterial causes of mycetoma is essential to advances in diagnosis and treatment. Here, we describe a high-quality genome assembly of M. mycetomatis and results of the whole genome sequence analysis of 26 isolates from Sudan. We demonstrate evidence of at least seven genetically diverse lineages and extreme clonality among isolates within these lineages. We also performed shotgun metagenomic analysis of DNA extracted from mycetoma grains and showed that M. mycetomatis reads were detected in all sequenced samples with the average of 11,317 reads (s.d. +/- 21,269) per sample. In addition, 10 (12%) of the 81 tested grain samples contained bacterial reads including Streptococcus sp., Staphylococcus sp. and others., Competing Interests: The authors have declared that no competing interests exist.

With this survey, we investigated healthcare-associated invasive mold infection (HA-IMI) surveillance and air sampling practices in US acute-care hospitals. More than half of surveyed facilities performed HA-IMI surveillance and air sampling. HA-IMI surveillance was more commonly performed in academic versus nonacademic facilities. HA-IMI case definitions and sampling strategies varied widely among respondents.

Background: Invasive mold diseases (IMDs) cause severe illness, but public health surveillance data are lacking. We describe data collected from a laboratory-based, pilot IMD surveillance system., Methods: During 2017-2019, the Emerging Infections Program conducted active IMD surveillance at 3 Atlanta-area hospitals. We ascertained potential cases by reviewing histopathology, culture, and Aspergillus galactomannan results and classified patients as having an IMD case (based on European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group [MSG] criteria) or a non-MSG IMD case (based on the treating clinician's diagnosis and use of mold-active antifungal therapy). We described patient features and compared patients with MSG vs non-MSG IMD cases., Results: Among 304 patients with potential IMD, 104 (34.2%) met an IMD case definition (41 MSG, 63 non-MSG). The most common IMD types were invasive aspergillosis (n = 66 [63.5%]), mucormycosis (n = 8 [7.7%]), and fusariosis (n = 4 [3.8%]); the most frequently affected body sites were pulmonary (n = 66 [63.5%]), otorhinolaryngologic (n = 17 [16.3%]), and cutaneous/deep tissue (n = 9 [8.7%]). Forty-five (43.3%) IMD patients received intensive care unit-level care, and 90-day all-cause mortality was 32.7%; these outcomes did not differ significantly between MSG and non-MSG IMD patients., Conclusions: IMD patients had high mortality rates and a variety of clinical presentations. Comprehensive IMD surveillance is needed to assess emerging trends, and strict application of MSG criteria for surveillance might exclude over one-half of clinically significant IMD cases., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

A common type of fungal disease investigation involves hospital-associated clusters of invasive mold infections (IMIs), which typically occur among immunocompromised patients. Responding to IMI clusters can be challenging for public health and hospital personnel for several reasons such as difficulty of confirming the existence of an outbreak, difficulty of determining source. Although many resources exist to guide patient notification about healthcare incidents (eg, bloodborne exposures, disease outbreaks), IMI clusters involve special considerations related to the complex diseases, uncertain exposures, and differential benefits and risks of notification. Early, nuanced communication about hospital-associated IMI clusters is almost always the best course of action to help reduce risks to patients' health and foster trust between patients and hospitals.

Background: The fungus Aspergillus fumigatus ( A. fumigatus ) is the leading cause of invasive mold infections, which cause severe disease and death in immunocompromised people. Use of triazole antifungal medications in recent decades has improved patient survival; however, triazole-resistant infections have become common in parts of Europe and are emerging in the United States. Triazoles are also a class of fungicides used in plant agriculture, and certain triazole-resistant A. fumigatus strains found causing disease in humans have been linked to environmental fungicide use., Objectives: We examined U.S. temporal and geographic trends in the use of triazole fungicides using U.S. Geological Survey agricultural pesticide use estimates., Discussion: Based on our analysis, overall tonnage of triazole fungicide use nationwide was relatively constant during 1992-2005 but increased > 4 -fold during 2006-2016 to 2.9   million   kg in 2016. During 1992-2005, triazole fungicide use occurred mostly in orchards and grapes, wheat, and other crops, but recent increases in use have occurred primarily in wheat, corn, soybeans, and other crops, particularly in Midwest and Southeast states. We conclude that, given the chemical similarities between triazole fungicides and triazole antifungal drugs used in human medicine, increased monitoring for environmental and clinical triazole resistance in A. fumigatus would improve overall understanding of these interactions, as well as help identify strategies to mitigate development and spread of resistance. https://doi.org/10.1289/EHP7484.

The Global Mycetoma Working Group (GMWG) was formed in January 2018 in response to the declaration of mycetoma as a neglected tropical disease (NTD) by the World Health Assembly. The aim of the working group is to connect experts and public health practitioners around the world to accelerate mycetoma prevention activities and reduce the impact of mycetoma on patients, healthcare providers and society in the endemic regions. The working group has made tangible contributions to mycetoma programming, awareness and coordination among scientists, clinicians and public health professionals. The group's connectivity has enabled rapid response and review of NTD documents in development, has created a network of public health professionals to provide regional mycetoma expertise and has enabled mycetoma to be represented within broader NTD organizations. The GMWG will continue to serve as a hub for networking and building collaborations for the advancement of mycetoma clinical management and treatment, research and public health programming., (Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene 2020.)

Cat-transmitted sporotrichosis caused by Sporothrix brasiliensis has become a major public health concern and presents a distinct divergence from the traditional epidemiology of sporotrichosis. This emerging fungal pathogen spreads readily among cat populations, and human infections occur exclusively via zoonotic transmission. While sporotrichosis is an implantation mycosis that typically manifests as cutaneous lesions in humans and cats, severe extracutaneous manifestations are more common with S. brasiliensis than other Sporothrix species infections. Rapid diagnosis and appropriate treatment regimens are critical for successful clinical resolution of sporotrichosis in both cats and humans. Species-level identification of Sporothrix is possible with molecular diagnostics and necessary for tracking the geographic expansion of S. brasiliensis and better understanding its epidemiology. Combatting cat-transmitted sporotrichosis requires a One Health approach to successfully implement public health control measures., Competing Interests: The authors declare no conflict of interest.

Objectives: Aspergillus coinfection in coronavirus disease 2019 patients has rarely been described but may be occurring among coronavirus disease 2019 patients admitted to ICUs. Previous reports of viral coinfections with Aspergillus , including influenza-associated pulmonary aspergillosis, suggest that coronavirus disease 2019-associated aspergillosis is plausible. This report aims to summarize what is known about coronavirus disease 2019 complicated by Aspergillus , introduces coronavirus disease 2019-associated pulmonary aspergillosis as a possible clinical entity, and describes reasons clinical suspicion of Aspergillus is warranted in the critical care setting., Data Sources: We summarize the available evidence suggesting the existence of Aspergillus coinfection among severe coronavirus disease 2019 patients. This includes published coronavirus disease 2019 patient case series, a case description, and a review of potential biologic mechanisms., Study Selection: Reports of coronavirus disease 2019 patient attributes were selected if they included clinical, microbiologic, or radiologic signs of invasive fungal infection., Data Extraction: Data included in summary tables were identified through a literature search for coronavirus disease 2019-associated pulmonary aspergillosis., Data Synthesis: We present descriptive data extracted from coronavirus disease 2019-associated pulmonary aspergillosis case series current at the time of article submission., Discussion: Pulmonary aspergillosis is known to occur among influenza patients requiring intensive care and is associated with increased mortality. If Aspergillus coinfections are occurring among coronavirus disease 2019 patients, early clinical suspicion and testing are needed to understand the epidemiology of these infections and prevent associated mortality. As the coronavirus disease 2019 pandemic unfolds, reports on the existence of this coinfection are needed, and opportunities to contribute cases of Aspergillus coinfection among coronavirus disease 2019 patients to an ongoing registry are described., Competing Interests: Dr. Verweij has received honoraria from Mundipharma, F2G, Pfizer, and Gliead Sciences paid to the institution; research grants from F2G, Pfizer, Thermofisher, and Gilead Sciences; and nonfinancial support from IMMY outside the submitted work. Dr. van de Veerdonk has received honoraria from Gliead Sciences. Dr. Wauters received speakers fee from Merck Sharp & Dohme (MSD), Pfizer, and Gilead; research grants from MSD and Pfizer; and nonfinancial support from MSD outside the submitted work. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. In response to the first cases identified in the United States, close contacts of confirmed COVID-19 cases were investigated to enable early identification and isolation of additional cases and to learn more about risk factors for transmission. Close contacts of nine early travel-related cases in the United States were identified and monitored daily for development of symptoms (active monitoring). Selected close contacts (including those with exposures categorized as higher risk) were targeted for collection of additional exposure information and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction at the Centers for Disease Control and Prevention. Four hundred four close contacts were actively monitored in the jurisdictions that managed the travel-related cases. Three hundred thirty-eight of the 404 close contacts provided at least basic exposure information, of whom 159 close contacts had ≥1 set of respiratory samples collected and tested. Across all actively monitored close contacts, two additional symptomatic COVID-19 cases (i.e., secondary cases) were identified; both secondary cases were in spouses of travel-associated case patients. When considering only household members, all of whom had ≥1 respiratory sample tested for SARS-CoV-2, the secondary attack rate (i.e., the number of secondary cases as a proportion of total close contacts) was 13% (95% CI: 4-38%). The results from these contact tracing investigations suggest that household members, especially significant others, of COVID-19 cases are at highest risk of becoming infected. The importance of personal protective equipment for healthcare workers is also underlined. Isolation of persons with COVID-19, in combination with quarantine of exposed close contacts and practice of everyday preventive behaviors, is important to mitigate spread of COVID-19., Competing Interests: The authors have declared that no competing interests exist.

Whole-genome sequencing confirmed the presence of a Malassezia pachydermatis outbreak among neonates in a neonatal intensive care unit. This technology supports the importance of adhering to infection prevention measures.

We investigated coccidioidomycosis testing and treatment patterns among persons in an integrated healthcare delivery system to identify gaps in diagnosis and treatment. Coccidioidomycosis diagnosis delays were common. Among persons who tested positive, 70% were prescribed antibiotics before positive coccidioidomycosis tests. Antibiotic treatment decreased and antifungal treatment increased after positive testing., (© The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

In an online survey, we found that nearly one fifth of physicians in the United States who responded had seen or heard about a case of invasive pulmonary aspergillosis after severe influenza at their institution. However, <10% routinely used galactomannan testing to test for this fungus in patients with severe influenza.

Purpose: To describe epidemiologic features of patients with presumed ocular histoplasmosis syndrome (POHS) in the United States using insurance claims data and compare POHS patients with and without choroidal neovascularization (CNV)., Design: Retrospective cohort study., Methods: Patients with International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for histoplasmosis retinitis on an outpatient claim in the 2014 IBM® MarketScan® Commercial Database and the Medicare Supplemental Database who were enrolled for at least 2 years after the POHS code., Main Outcome Measures: Data related to testing, treatment, and direct medical costs., Results: Among >50 million total MarketScan enrollees, 6,678 (13 per 100,000) had a POHS diagnosis code. Of those, 2,718 were enrolled for 2 years; 698 (25%) of whom had a CNV code. Eleven of the 13 states with the highest POHS rates bordered the Mississippi and Ohio rivers. CNV patients had significantly more eye care provider visits (mean 8.8 vs. 3.2, p<0.0001), more ophthalmic imaging tests, higher rates of treatment with anti-vascular endothelial growth factor injections (45% vs. 4%, p<0.0001), and incurred higher mean total yearly costs ($1,251.83 vs. $251.36, p<0.0001) than POHS patients without CNV., Conclusions: Although the relationship between Histoplasma and POHS remains controversial, geographic patterns of POHS patient residence were consistent with the traditionally reported range of the fungus. CNV in the context of POHS was associated with additional healthcare use and costs. Further research to understand POHS etiology, risk factors, prevalence, and complications is needed, along with early diagnosis and treatment strategies., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Jessica G. Shantha: Santen Inc. Consultant. Steven Yeh: Clearside Biomedical; Santen. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Infections with Histoplasma can range from asymptomatic to life-threatening acute pulmonary or disseminated disease. Histoplasmosis can be challenging to diagnose and is widely underrecognized. We analyzed insurance claims data to better characterize histoplasmosis testing and treatment practices and its burden on patients., Methods: We used the IBM MarketScan Research Databases to identify patients with histoplasmosis (International Classification of Diseases, Ninth Revision, Clinical Modification codes 115.00-115.99) during 2012-2014. We analyzed claims in the 3 months before to the 1 year after diagnosis and examined differences between patients with probable (hospitalized or >1 outpatient visit) and suspected (1 outpatient visit) histoplasmosis., Results: Among 1935 patients (943 probable, 992 suspected), 54% had codes for symptoms or findings consistent with histoplasmosis and 35% had ≥2 healthcare visits in the 3 months before diagnosis. Overall, 646 (33%) had any fungal-specific laboratory test: histoplasmosis antibody test (n = 349 [18%]), Histoplasma antigen test (n = 349 [18%]), fungal smear (n = 294 [15%]), or fungal culture (n = 223 [12%]); 464 (24%) had a biopsy. Forty-nine percent of probable patients and 10% of suspected patients were prescribed antifungal medication in the outpatient setting. In total, 19% were hospitalized. Patients' last histoplasmosis-associated healthcare visits occurred a median of 6 months after diagnosis., Conclusions: Some histoplasmosis patients experienced severe disease, apparent diagnostic delays, and prolonged illness, whereas other patients lacked symptoms and were likely diagnosed incidentally (eg, via biopsy). Low rates of histoplasmosis-specific testing also suggest incidental diagnoses and low provider suspicion, highlighting the need for improved awareness about this disease., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

This report serves as a guide for investigating mucormycosis infections in healthcare. We describe lessons learned from previous outbreaks and offer methods and tools that can aid in these investigations. We also offer suggestions for conducting environmental assessments, implementing infection control measures, and initiating surveillance to ensure that interventions were effective. While not all investigations of mucormycosis infections will identify a single source, all can potentially lead to improvements in infection control.

In August 2017, Hurricane Harvey caused unprecedented flooding and devastation to the Houston metropolitan area (1). Mold exposure was a serious concern because investigations after Hurricanes Katrina and Rita (2005) had documented extensive mold growth in flood-damaged homes (2,3). Because mold exposure can cause serious illnesses known as invasive mold infections (4,5), and immunosuppressed persons are at high risk for these infections (6,7), several federal agencies recommend that immunosuppressed persons avoid mold-contaminated sites (8,9). To assess the extent of exposure to mold and flood-damaged areas among persons at high risk for invasive mold infections after Hurricane Harvey, CDC and Texas health officials conducted a survey among 103 immunosuppressed residents in Houston. Approximately half of the participants (50) engaged in cleanup of mold and water-damaged areas; these activities included heavy cleanup (23), such as removing furniture or removing drywall, or light cleanup (27), such as wiping down walls or retrieving personal items. Among immunosuppressed persons who performed heavy cleanup, 43% reported wearing a respirator, as did 8% who performed light cleanup. One participant reported wearing all personal protective equipment (PPE) recommended for otherwise healthy persons (i.e., respirator, boots, goggles, and gloves). Immunosuppressed residents who are at high risk for invasive mold infections were exposed to mold and flood-damaged areas after Hurricane Harvey; recommendations from health care providers to avoid exposure to mold and flood-damaged areas could mitigate the risk to immunosuppressed persons., Competing Interests: Luis Ostrosky-Zeichner reports grants and personal fees from Astellas, personal fees from Merck & Co., grants and personal fees from Pfizer, grants and personal fees from Cidara, grants and personal fees from Scynexis, personal fees from F2G, grants from Amplyx, personal fees from Mayne, personal fees from Gilead, personal fees from NovaDigm, personal fees from United Medical, and personal fees from Stendhal outside the submitted work. Dimitrios P. Kontoyiannis reports honoraria for lectures from Merck & Co., Gilead, and United Medicine and also reports consulting fees from Merck & Co., Astellas, Cidara, Amplyx, and Mayne. No other potential conflicts of interest were disclosed.

Background: Fungal diseases range from relatively-minor superficial and mucosal infections to severe, life-threatening systemic infections. Delayed diagnosis and treatment can lead to poor patient outcomes and high medical costs. The overall burden of fungal diseases in the United States is challenging to quantify, because they are likely substantially underdiagnosed., Methods: To estimate the total, national, direct medical costs associated with fungal diseases from a healthcare payer perspective, we used insurance claims data from the Truven Health MarketScan 2014 Research Databases, combined with hospital discharge data from the 2014 Healthcare Cost and Utilization Project National Inpatient Sample and outpatient visit data from the 2005-2014 National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. All costs were adjusted to 2017 dollars., Results: We estimate that fungal diseases cost more than $7.2 billion in 2017, including $4.5 billion from 75055 hospitalizations and $2.6 billion from 8993230 outpatient visits. Hospitalizations for Candida infections (n = 26735, total cost $1.4 billion) and Aspergillus infections (n = 14820, total cost $1.2 billion) accounted for the highest total hospitalization costs of any disease. Over half of outpatient visits were for dermatophyte infections (4981444 visits, total cost $802 million), and 3639037 visits occurred for non-invasive candidiasis (total cost $1.6 billion)., Conclusions: Fungal diseases impose a considerable economic burden on the healthcare system. Our results likely underestimate their true costs, because they are underdiagnosed. More comprehensive estimates of the public health impact of these diseases are needed to improve their recognition, prevention, diagnosis, and treatment., (Published by Oxford University Press for the Infectious Diseases Society of America 2018.)

The environmental mold Aspergillus fumigatus is the primary cause of invasive aspergillosis. In patients with high-risk conditions, including stem cell and organ transplant recipients, mortality exceeds 50%. Triazole antifungals have greatly improved survival (1); however, triazole-resistant A. fumigatus infections are increasingly reported worldwide and are associated with increased treatment failure and mortality (2). Of particular concern are resistant A. fumigatus isolates carrying either TR 34 /L98H or TR 46 /Y121F/T289A genetic resistance markers, which have been associated with environmental triazole fungicide use rather than previous patient exposure to antifungals (3,4). Reports of these triazole-resistant A. fumigatus strains have become common in Europe (2,3), but U.S. reports are limited (5). Because of the risk posed to immunocompromised patients, understanding the prevalence of such isolates in patients is important to guide clinical and public health decision-making. In 2011, CDC initiated passive laboratory monitoring for U.S. triazole-resistant A. fumigatus isolates through outreach to clinical laboratories. This system identified five TR 34 /L98H isolates collected from 2016 to 2017 (6), in addition to two other U.S. isolates collected in 2010 and 2014 and reported in 2015 (5). Four of these seven isolates were reported from Pennsylvania, two from Virginia, and one from California. Three isolates were collected from patients with invasive pulmonary aspergillosis, and four patients had no known previous triazole exposure. A. fumigatus resistant to all triazole medications is emerging in the United States, and clinicians and public health personnel need to be aware that resistant infections are possible even in patients not previously exposed to these medications., Competing Interests: All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Infections caused by pan-azole-resistant Aspergillus fumigatus strains have emerged in Europe and recently in the United States. Physicians specializing in infectious diseases reported observing pan-azole-resistant infections and low rates of susceptibility testing, suggesting the need for wider-scale testing.

Adaptive prediction is a capability of diverse organisms, including microbes, to sense a cue and prepare in advance to deal with a future environmental challenge. Here, we investigated the timeframe over which adaptive prediction emerges when an organism encounters an environment with novel structure. We subjected yeast to laboratory evolution in a novel environment with repetitive, coupled exposures to a neutral chemical cue (caffeine), followed by a sublethal dose of a toxin (5-FOA), with an interspersed requirement for uracil prototrophy to counter-select mutants that gained constitutive 5-FOA resistance. We demonstrate the remarkable ability of yeast to internalize a novel environmental pattern within 50-150 generations by adaptively predicting 5-FOA stress upon sensing caffeine. We also demonstrate how novel environmental structure can be internalized by coupling two unrelated response networks, such as the response to caffeine and signaling-mediated conditional peroxisomal localization of proteins., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Background: Giardiasis, the most common enteric parasitic infection in the United States, causes an estimated 1.2 million episodes of illness annually. Published clinical recommendations include readily available Giardia-specific diagnostic testing and antiparasitic drugs. We investigated sequences of giardiasis diagnostic and treatment events using MarketScan, a large health insurance claims database., Methods: We created a longitudinal cohort of 2995 persons diagnosed with giardiasis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 007.1) from 2006 to 2010, and analyzed claims occurring 90 days before to 90 days after initial diagnosis. We evaluated differences in number and sequence of visits, diagnostic tests, and prescriptions by age group (children 1-17 years, adults 18-64 years) using χ2 tests and data visualization software., Results: Among 2995 patients (212433 claims), 18% had a Giardia-specific test followed by or concurrent with an effective antiparasitic drug, without ineffective antibiotics. Almost two-thirds of patients had an antiparasitic and 27% had an antibiotic during the study window. Compared with children, adults more often had ≥3 visits before diagnosis (19% vs 15%; P = .02). Adults were also less likely to have a Giardia-specific diagnostic test (48% vs 58%; P < .001) and more likely to have an antibiotic prescription (28% vs 25%; P = .04). When Giardia-specific tests and antiparasitic and antibiotic prescriptions were examined, pediatric clinical event sequences most frequently began with a Giardia-specific test, whereas adult sequences most frequently began with an antiparasitic prescription., Conclusions: Giardiasis care infrequently follows all aspects of clinical recommendations. Multiple differences between pediatric and adult care, despite age-agnostic recommendations, suggest opportunities for provider education or tailored guidance., (Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: In June 2014, the mosquito-borne chikungunya virus (CHIKV) emerged in the U.S. Virgin Islands (USVI), a location where tourists comprise the majority of the population during peak season (January-April). Limited information is available concerning visitors' CHIKV awareness and prevention measures., Methods: We surveyed a convenience sample of Virgin Islands National Park visitors aged ≥18 years. Respondents completed a questionnaire assessing CHIKV knowledge, attitudes, and practices; health information-seeking practices; and demographics., Results: Of 783 persons contacted, 443 (57%) completed the survey. Fewer than half (208/441 [47%]) were aware of CHIKV. During trip preparation, 28% of respondents (126/443) investigated USVI-specific health concerns. Compared with persons unaware of CHIKV, CHIKV-aware persons were more likely to apply insect repellent (134/207 [65%] versus 111/231 [48%]; p < 0.001), wear long-sleeves and long pants (84/203 [41%] versus 57/227 [25%]; p < 0.001), and wear insect repellent-treated clothing (36/204 [18%] versus 22/227 [10%]; p = 0.02)., Conclusions: The majority of visitors surveyed did not research destination-related health concerns and were unaware of CHIKV. However, CHIKV awareness was associated with using multiple prevention measures to reduce disease risk. These findings underscore the importance of providing tourists with disease education upon destination arrival., Competing Interests: None., (Published by Elsevier Ltd.)

Populations of organisms routinely face abiotic selection pressures, and a central goal of evolutionary biology is to understand the mechanistic underpinnings of adaptive phenotypes. Ultraviolet radiation (UVR) is one of earth's most pervasive environmental stressors, potentially damaging DNA in any organism exposed to solar radiation. We explored mechanisms underlying differential survival following UVR exposure in genotypes of the water flea Daphnia melanica derived from natural ponds of differing UVR intensity. The UVR tolerance of a D. melanica genotype from a high-UVR habitat depended on the presence of visible and UV-A light wavelengths necessary for photoenzymatic repair of DNA damage, a repair pathway widely shared across the tree of life. We then measured the acquisition and repair of cyclobutane pyrimidine dimers, the primary form of UVR-caused DNA damage, in D. melanica DNA following experimental UVR exposure. We demonstrate that genotypes from high-UVR habitats repair DNA damage faster than genotypes from low-UVR habitats in the presence of visible and UV-A radiation necessary for photoenzymatic repair, but not in dark treatments. Because differences in repair rate only occurred in the presence of visible and UV-A radiation, we conclude that differing rates of DNA repair, and therefore differential UVR tolerance, are a consequence of variation in photoenzymatic repair efficiency. We then rule out a simple gene expression hypothesis for the molecular basis of differing repair efficiency, as expression of the CPD photolyase gene photorepair did not differ among D. melanica lineages, in both the presence and absence of UVR., (© 2015 John Wiley & Sons Ltd.)

Advances in water management and sanitation have substantially reduced waterborne disease in the United States, although outbreaks continue to occur. Public health agencies in the U.S. states and territories* report information on waterborne disease outbreaks to the CDC Waterborne Disease and Outbreak Surveillance System (http://www.cdc.gov/healthywater/surveillance/index.html). For 2011-2012, 32 drinking water-associated outbreaks were reported, accounting for at least 431 cases of illness, 102 hospitalizations, and 14 deaths. Legionella was responsible for 66% of outbreaks and 26% of illnesses, and viruses and non-Legionella bacteria together accounted for 16% of outbreaks and 53% of illnesses. The two most commonly identified deficiencies† leading to drinking water-associated outbreaks were Legionella in building plumbing§ systems (66%) and untreated groundwater (13%). Continued vigilance by public health, regulatory, and industry professionals to identify and correct deficiencies associated with building plumbing systems and groundwater systems could prevent most reported outbreaks and illnesses associated with drinking water systems.

Exposures to contaminated water can lead to waterborne disease outbreaks associated with various sources, including many that are classified and reported separately as drinking water or recreational water. Waterborne disease outbreaks can also involve a variety of other exposures (e.g., consuming water directly from backcountry or wilderness streams, or inhaling aerosols from cooling towers and ornamental fountains). Additionally, outbreaks might be epidemiologically linked to multiple water sources or may not have a specific water source implicated.

On April 21, 2015, the Fairfield Medical Center (FMC) and Fairfield Department of Health contacted the Ohio Department of Health (ODH) about a patient suspected of having botulism in Fairfield County, Ohio. Botulism is a severe, potentially fatal neuroparalytic illness.* A single case is a public health emergency, because it can signal an outbreak. Within 2 hours of health department notification, four more patients with similar clinical features arrived at FMC's emergency department. Later that afternoon, one patient died of respiratory failure shortly after arriving at the emergency department. All affected persons had eaten at the same widely attended church potluck meal on April 19. CDC's Strategic National Stockpile sent 50 doses of botulinum antitoxin to Ohio. FMC, the Fairfield Department of Health, ODH, and CDC rapidly responded to confirm the diagnosis, identify and treat additional patients, and determine the source.

As of July 1, 2015, Guinea, Liberia, and Sierra Leone have reported a total of 27,443 confirmed, probable, and suspected Ebola virus disease (Ebola) cases and 11,220 deaths. Guinea and Sierra Leone have yet to interrupt transmission of Ebola virus. In January, 2016, Liberia successfully achieved Ebola transmission-free status, with no new Ebola cases occurring during a 42-day period; however, new Ebola cases were reported beginning June 29, 2015. Local cultural practices and beliefs have posed challenges to disease control, and therefore, targeted, timely health messages are needed to address practices and misperceptions that might hinder efforts to stop the spread of Ebola. As early as September 2014, Ebola spread to most counties in Liberia. To assess Ebola-related knowledge, attitudes, and practices (KAP) in the community, CDC epidemiologists who were deployed to the counties (field team), carried out a survey conducted by local trained interviewers. The survey was conducted in September and October 2014 in five counties in Liberia with varying cumulative incidence of Ebola cases. Survey results indicated several findings. First, basic awareness of Ebola was high across all surveyed populations (median correct responses = 16 of 17 questions on knowledge of Ebola transmission; range = 2-17). Second, knowledge and understanding of Ebola symptoms were incomplete (e.g., 61% of respondents said they would know if they had Ebola symptoms). Finally, certain fears about the disease were present: >90% of respondents indicated a fear of Ebola patients, >40% a fear of cured patients, and >50% a fear of treatment units (expressions of this last fear were greater in counties with lower Ebola incidence). This survey, which was conducted at a time when case counts were rapidly increasing in Liberia, indicated limited knowledge of Ebola symptoms and widespread fear of Ebola treatment units despite awareness of communication messages. Continued efforts are needed to address cultural practices and beliefs to interrupt Ebola transmission.

Background: Expansion of transcription factors is believed to have played a crucial role in evolution of all organisms by enabling them to deal with dynamic environments and colonize new environments. We investigated how the expansion of the Feast/Famine Regulatory Protein (FFRP) or Lrp-like proteins into an eight-member family in Halobacterium salinarum NRC-1 has aided in niche-adaptation of this archaeon to a complex and dynamically changing hypersaline environment., Results: We mapped genome-wide binding locations for all eight FFRPs, investigated their preference for binding different effector molecules, and identified the contexts in which they act by analyzing transcriptional responses across 35 growth conditions that mimic different environmental and nutritional conditions this organism is likely to encounter in the wild. Integrative analysis of these data constructed an FFRP regulatory network with conditionally active states that reveal how interrelated variations in DNA-binding domains, effector-molecule preferences, and binding sites in target gene promoters have tuned the functions of each FFRP to the environments in which they act. We demonstrate how conditional regulation of similar genes by two FFRPs, AsnC (an activator) and VNG1237C (a repressor), have striking environment-specific fitness consequences for oxidative stress management and growth, respectively., Conclusions: This study provides a systems perspective into the evolutionary process by which gene duplication within a transcription factor family contributes to environment-specific adaptation of an organism.

Ebola virus disease (Ebola) is a multisystem disease caused by a virus of the genus Ebolavirus. In late March 2014, Ebola cases were described in Liberia, with epicenters in Lofa County and later in Montserrado County. While information about case burden and health care infrastructure was available for the two epicenters, little information was available about remote counties in southeastern Liberia. Over 9 days, August 6-14, 2014, Ebola case burden, health care infrastructure, and emergency preparedness were assessed in collaboration with the Liberian Ministry of Health and Social Welfare in four counties in southeastern Liberia: Grand Gedeh, Grand Kru, River Gee, and Maryland. Data were collected by health care facility visits to three of the four county referral hospitals and by unstructured interviews with county and district health officials, hospital administrators, physicians, nurses, physician assistants, and health educators in all four counties. Local burial practices were discussed with county officials, but no direct observation of burial practices was conducted. Basic information about Ebola surveillance and epidemiology, case investigation, contact tracing, case management, and infection control was provided to local officials.

It is known that environmental context influences the degree of regulation at the transcriptional and post-transcriptional levels. However, the principles governing the differential usage and interplay of regulation at these two levels are not clear. Here, we show that the integration of transcriptional and post-transcriptional regulatory mechanisms in a characteristic network motif drives efficient environment-dependent state transitions. Through phenotypic screening, systems analysis, and rigorous experimental validation, we discovered an RNase (VNG2099C) in Halobacterium salinarum that is transcriptionally co-regulated with genes of the aerobic physiologic state but acts on transcripts of the anaerobic state. Through modelling and experimentation we show that this arrangement generates an efficient state-transition switch, within which RNase-repression of a transcriptional positive autoregulation (RPAR) loop is critical for shutting down ATP-consuming active potassium uptake to conserve energy required for salinity adaptation under aerobic, high potassium, or dark conditions. Subsequently, we discovered that many Escherichia coli operons with energy-associated functions are also putatively controlled by RPAR indicating that this network motif may have evolved independently in phylogenetically distant organisms. Thus, our data suggest that interplay of transcriptional and post-transcriptional regulation in the RPAR motif is a generalized principle for efficient environment-dependent state transitions across prokaryotes., (© 2014 John Wiley & Sons Ltd.)

Although tractable model organisms are essential to characterize the molecular mechanisms of evolution and adaptation, the ecological relevance of their behavior is not always clear because certain traits are easily lost during long-term laboratory culturing. Here, we demonstrate that despite their long tenure in the laboratory, model organisms retain "ecological memory" of complex environmental changes. We have discovered that Halobacterium salinarum NRC-1, a halophilic archaeon that dominates microbial communities in a dynamically changing hypersaline environment, simultaneously optimizes fitness to total salinity, NaCl concentration, and the [K]/[Mg] ratio. Despite being maintained under controlled conditions over the last 50 years, peaks in the three-dimensional fitness landscape occur in salinity and ionic compositions that are not replicated in laboratory culturing but are routinely observed in the natural hypersaline environment of this organism. Intriguingly, adaptation to variations in ion composition was associated with differential regulation of anaerobic metabolism genes, suggesting an intertwined relationship between responses to oxygen and salinity. Our results suggest that the ecological memory of complex environmental variations is imprinted in the networks for coordinating multiple cellular processes. These coordination networks are also essential for dealing with changes in other physicochemically linked factors present during routine laboratory culturing and, hence, retained in model organisms.

The prediction and verification of adaptive trajectories on macroevolutionary timescales have rarely been achieved for complex biological systems. Employing a model linking biological information at multiple scales, Heckmann et al. simulate likely sequences of evolutionary changes from C3 to C4 photosynthesis biochemistry., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The evolutionary success of an organism is a testament to its inherent capacity to keep pace with environmental conditions that change over short and long periods. Mechanisms underlying adaptive processes are being investigated with renewed interest and excitement. This revival is partly fueled by powerful technologies that can probe molecular phenomena at a systems scale. Such studies provide spectacular insight into the mechanisms of adaptation, including rewiring of regulatory networks via natural selection of horizontal gene transfers, gene duplication, deletion, readjustment of kinetic parameters, and myriad other genetic reorganizational events. Here, we discuss advances in prokaryotic systems biology from the perspective of evolutionary principles that have shaped regulatory networks for dynamic adaptation to environmental change., (Copyright © 2010 John Wiley & Sons, Inc.)