Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-30 (of 39 Records) |
Query Trace: Chandler G[original query] |
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Using geographic disaggregation to compare tuberculosis epidemiology among American Indian and Alaska native persons-USA, 2010-2020
Springer YP , Kammerer JS , Felix D , Newell K , Tompkins ML , Allison J , Castrodale LJ , Chandler B , Helfrich K , Rothoff M , McLaughlin JB , Silk BJ . J Racial Ethn Health Disparities 2024 BACKGROUND: American Indian and Alaska Native (AIAN) populations are frequently associated with the highest rates of tuberculosis (TB) disease of any racial/ethnic group in the USA. We systematically investigated variation in patterns and potential drivers of TB epidemiology among geographically distinct AIAN subgroups. METHODS: Using data reported to the National Tuberculosis Surveillance System during 2010-2020, we applied a geographic method of data disaggregation to compare annual TB incidence and the frequency of TB patient characteristics among AIAN persons in Alaska with AIAN persons in other states. We used US Census data to compare the prevalence of substandard housing conditions in AIAN communities in these two geographic areas. RESULTS: The average annual age-adjusted TB incidence among AIAN persons in Alaska was 21 times higher than among AIAN persons in other states. Compared to AIAN TB patients in other states, AIAN TB patients in Alaska were associated with significantly higher frequencies of multiple epidemiologic TB risk factors (e.g., attribution of TB disease to recent transmission, previous diagnosis of TB disease) and significantly lower frequencies of multiple clinical risk factors for TB disease (e.g., diagnosis with diabetes mellitus, end-stage renal disease). Occupied housing units in AIAN communities in Alaska were associated with significantly higher frequencies of multiple measures of substandard housing conditions compared to AIAN communities in other states. CONCLUSIONS: Observed differences in patient characteristics and substandard housing conditions are consistent with contrasting syndromes of TB epidemiology in geographically distinct AIAN subgroups and suggest ways that associated public health interventions could be tailored to improve efficacy. |
Association between SARS-CoV-2 variants and frequency of acute symptoms: Analysis of a multi-institutional prospective cohort study-December 20, 2020-June 20, 2022
Wang RC , Gottlieb M , Montoy JCC , Rodriguez RM , Yu H , Spatz ES , Chandler CW , Elmore JG , Hannikainen PA , Chang AM , Hill M , Huebinger RM , Idris AH , Koo K , Li SX , McDonald S , Nichol G , O'Laughlin KN , Plumb ID , Santangelo M , Saydah S , Stephens KA , Venkatesh AK , Weinstein RA . Open Forum Infect Dis 2023 10 (7) ofad275 BACKGROUND: While prior work examining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern focused on hospitalization and death, less is known about differences in clinical presentation. We compared the prevalence of acute symptoms across pre-Delta, Delta, and Omicron. METHODS: We conducted an analysis of the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), a cohort study enrolling symptomatic SARS-CoV-2-positive participants. We determined the association between the pre-Delta, Delta, and Omicron time periods and the prevalence of 21 coronavirus disease 2019 (COVID-19) acute symptoms. RESULTS: We enrolled 4113 participants from December 2020 to June 2022. Pre-Delta vs Delta vs Omicron participants had increasing sore throat (40.9%, 54.6%, 70.6%; P < .001), cough (50.9%, 63.3%, 66.7%; P < .001), and runny noses (48.9%, 71.3%, 72.9%; P < .001). We observed reductions during Omicron in chest pain (31.1%, 24.2%, 20.9%; P < .001), shortness of breath (42.7%, 29.5%, 27.5%; P < .001), loss of taste (47.1%, 61.8%, 19.2%; P < .001), and loss of smell (47.5%, 55.6%, 20.0%; P < .001). After adjustment, those infected during Omicron had significantly higher odds of sore throat vs pre-Delta (odds ratio [OR], 2.76; 95% CI, 2.26-3.35) and Delta (OR, 1.96; 95% CI, 1.69-2.28). CONCLUSIONS: Participants infected during Omicron were more likely to report symptoms of common respiratory viruses, such as sore throat, and less likely to report loss of smell and taste. TRIAL REGISTRATION: NCT04610515. |
Transmission of SARS-CoV-2 in free-ranging white-tailed deer in the United States
Feng A , Bevins S , Chandler J , DeLiberto TJ , Ghai R , Lantz K , Lenoch J , Retchless A , Shriner S , Tang CY , Tong SS , Torchetti M , Uehara A , Wan XF . Nat Commun 2023 14 (1) 4078 SARS-CoV-2 is a zoonotic virus with documented bi-directional transmission between people and animals. Transmission of SARS-CoV-2 from humans to free-ranging white-tailed deer (Odocoileus virginianus) poses a unique public health risk due to the potential for reservoir establishment where variants may persist and evolve. We collected 8,830 respiratory samples from free-ranging white-tailed deer across Washington, D.C. and 26 states in the United States between November 2021 and April 2022. We obtained 391 sequences and identified 34 Pango lineages including the Alpha, Gamma, Delta, and Omicron variants. Evolutionary analyses showed these white-tailed deer viruses originated from at least 109 independent spillovers from humans, which resulted in 39 cases of subsequent local deer-to-deer transmission and three cases of potential spillover from white-tailed deer back to humans. Viruses repeatedly adapted to white-tailed deer with recurring amino acid substitutions across spike and other proteins. Overall, our findings suggest that multiple SARS-CoV-2 lineages were introduced, became enzootic, and co-circulated in white-tailed deer. |
Lessons Learned through Implementing SARS-CoV-2 Testing and Isolation for People Experiencing Homelessness in Congregate Shelters.
Scott E , Rowan S , Chandler K , Fisher A , Hill B , Hill J , Marx GE , Farrell E , Wendel K , Stella SA . Prog Community Health Partnersh 2022 16 13-22 BACKGROUND: The Denver COVID-19 Joint Task Force is a multisector community partnership which formed to coordinate Denver's pandemic response in people experiencing homelessness (PEH). OBJECTIVES: Describe how interdisciplinary community partners collaborated to develop, implement, and pilot severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing and isolation protocols in congregate shelters, and discuss lessons learned and subsequently applied. METHODS: In March through May 2020, community partners collaborated to design, implement and conduct pilot testing paired with isolation in a subset of PEH at a congregate shelter to assess feasibility and inform protocol development.Results and Lessons Learned: We performed SARS-CoV-2 testing in 52 PEH with 14 (27%) testing positive or inconclusive. Thirteen (93%) positive or inconclusive participants were transferred to isolation hotels with 9 of 13 (69%) transferred within 72 hours of testing. CONCLUSIONS: Our findings informed development of coronavirus disease 2019 surveillance testing and isolation protocols for PEH and highlight the value of community partnerships in nimbly responding to the pandemic. |
Early and increased influenza activity among children - Tennessee, 2022-23 influenza season
Thomas CM , White EB , Kojima N , Fill MA , Hanna S , Jones TF , Newhouse CN , Orejuela K , Roth E , Winders S , Chandler DR , Grijalva CG , Schaffner W , Schmitz JE , DaSilva J , Kirby MK , Mellis AM , Rolfes MA , Sumner KM , Flannery B , Talbot HK , Dunn JR . MMWR Morb Mortal Wkly Rep 2023 72 (3) 49-54 Influenza seasons typically begin in October and peak between December and February (1); however, the 2022-23 influenza season in Tennessee began in late September and was characterized by high pediatric hospitalization rates during November. This report describes a field investigation conducted in Tennessee during November 2022, following reports of increasing influenza hospitalizations. Data from surveillance networks, patient surveys, and whole genome sequencing of influenza virus specimens were analyzed to assess influenza activity and secondary illness risk. Influenza activity increased earlier than usual among all age groups, and rates of influenza-associated hospitalization among children were high in November, reaching 12.6 per 100,000 in children aged <5 years, comparable to peak levels typically seen in high-severity seasons. Circulating influenza viruses were genetically similar to vaccine components. Among persons who received testing for influenza at outpatient clinics, children were twice as likely to receive a positive influenza test result as were adults. Among household contacts exposed to someone with influenza, children were more than twice as likely to become ill compared with adults. As the influenza season continues, it is important for all persons, especially those at higher risk for severe disease, to protect themselves from influenza. To prevent influenza and severe influenza complications, all persons aged ≥6 months should get vaccinated, avoid contact with ill persons, and take influenza antivirals if recommended and prescribed. |
Electronic messaging for gonorrhea and chlamydia test result notification, improving treatment and patient satisfaction
Rahman MM , Johnson C , Whyte M , Ewell J , Cope AB , Chandler Y , Bennett TS , Gray T , Gruber D , Peterman TA . Sex Transm Dis 2021 49 (4) 257-261 BACKGROUND: Approximately 20% of chlamydia (CT) and gonorrhea (GC) cases in Louisiana are diagnosed at Parish Health Units (PHU). Patient notification of CT and GC test results involves nurses' phone calls and letters to positive patients, which is time consuming and inefficient. METHODS: In December 2018, electronic results notification was implemented in Caddo PHU using Chexout software to notify enrolled patients via text or email when test results are ready to view in a patient portal. We compared the timeliness of GC/CT results notification and treatment pre- (December 2017-November 2018) and post- (December 2018-November 2019) Chexout implementation. A random sample of patients were interviewed to assess acceptability. RESULTS: During December 2018 - November 2019, 5,432 patients were tested for CT/GC, 3,924 (72%) enrolled in Chexout, and notifications were sent to 3,884 (99%). Among CT positives, 472/568 (83%) viewed results in the portal compared to 2,451/3,356 (73%) CT negatives. Among GC positives, 300/353 (85%) viewed results compared to 2,657/3,571 (74%) GC negatives. Treatment success for CT improved from 493/670 (74%) to 506/568 (89%) and for GC from 332/409 (81%) to 325/353 (92%). Mean time to treatment decreased for CT (13.4 to 10.7 days) and GC (11.3 to 9.2 days). Enrolled patients found Chexout notification satisfactory 168/169 (99%) and easy to use 130/141 (92%). Reasons for declining electronic notification included lack of personal cell phone 55/86 (64%) and confidentiality concerns 42/86 (49%). CONCLUSIONS: Electronic messaging decreased time to notification and increased treatment success. Nurses spent less time notifying patients leaving more time for patient care. |
Reproductive hormone concentrations and associated anatomical responses: does soy formula affect minipuberty in boys
Chin HB , Kelly A , Adgent MA , Patchel SA , James K , Vesper HW , Botelho JC , Chandler DW , Zemel BS , Schall JI , Ford EG , Darge K , Stallings VA , Baird DD , Rogan WJ , Umbach DM . J Clin Endocrinol Metab 2021 106 (9) 2635-2645 CONTEXT: Soy formula feeding is common in infancy and is a source of high exposure to phytoestrogens, documented to influence vaginal cytology in female infants. Its influence on minipuberty in males has not been established. OBJECTIVE: To assess the association between infant feeding practice and longitudinally measured reproductive hormones and hormone-responsive tissues in infant boys. DESIGN: The Infant Feeding and Early Development study was a prospective cohort of maternal-infant dyads requiring exclusive soy formula, cow-milk formula, or breastmilk feeding during study follow-up. Reproductive hormone concentrations and male anatomical measurements were longitudinally assessed from birth to 28 weeks. SETTING: Clinic-based cohort. PARTICIPANTS: 147 mother-infant boy pairs. INTERVENTIONS: not applicable. MAIN OUTCOME MEASURE: Serum testosterone and luteinizing hormone (LH) concentrations, stretched penile length, anogenital distance, and testis volume. RESULTS: Median serum testosterone was at pubertal levels at 2 weeks [176 ng/dL (quartiles:124, 232)] and remained in this range until 12 weeks, in all feeding groups. We did not observe differences in trajectories of hormone concentrations or anatomical measures between boys fed soy formula (n=55) and boys fed cow-milk formula (n=54). Compared with breastfed boys (n=38), soy-formula-fed boys had a more rapid increase in penile length (p=0.004) and slower initial lengthening of AGD (p=0.03), but no differences in hormone trajectories. CONCLUSIONS: Reproductive hormone concentrations and anatomical responses followed similar trajectories in soy and cow-milk formula-fed infant boys. Our findings suggest that these measures of early male reproductive development do not respond to phytoestrogen exposure during infancy. |
Progress in Immunization Safety Monitoring - Worldwide, 2010-2019
Salman O , Topf K , Chandler R , Conklin L . MMWR Morb Mortal Wkly Rep 2021 70 (15) 547-551 High levels of coverage with safe and effective immunizations are critical to the successful control and prevention of vaccine-preventable diseases worldwide. In addition to stringent standards to regulate the safety of vaccines, robust postlicensure monitoring systems help ensure that the benefits of vaccines continue to outweigh the risks for the populations who receive them. National Expanded Programmes on Immunization (EPI) are typically responsible for identifying and investigating adverse events following immunization (AEFI), including assessment of causality. National regulatory authorities (NRAs) are mandated to perform postlicensure surveillance of adverse drug reactions, including those associated with receipt of vaccines. This report describes global progress toward meeting World Health Organization (WHO) indicators on minimal country capacity for vaccine safety surveillance and coordination of AEFI reporting between countries' EPI and NRAs. In 2019, among 194 countries, 129 (66.5%) reported having an operational national AEFI causality review committee, compared with 94 (48.5%) in 2010. During 2010-2019, the proportion of countries reporting ≥10 AEFI per 100,000 surviving infants per year (an indicator of country capacity to monitor immunization safety) increased, from 41.2% to 56.2%. In 2019, however, only 46 (23.7%) countries reported AEFI data from both EPI and NRAs. Although global progress has been made toward strengthening systems for vaccine safety monitoring over the past decade, new indicators for monitoring global immunization safety performance are needed to better reflect program functionality. Continued global efforts will be vital to address barriers to routine reporting of AEFI, build national capacity for AEFI investigation and data management, and improve sharing of AEFI data at national, regional, and global levels. |
The 2017 solar eclipse: Implementing enhanced syndromic surveillance on the path of totality in Kentucky
Heitzinger K , Thoroughman DA , Johnson BD , Chandler A , Prather JW , Walls HM , Robeson SD , Porter KA . Disaster Med Public Health Prep 2020 15 (2) 1-4 OBJECTIVE: The 2017 solar eclipse was associated with mass gatherings in many of the 14 states along the path of totality. The Kentucky Department for Public Health implemented an enhanced syndromic surveillance system to detect increases in emergency department (ED) visits and other health care needs near Hopkinsville, Kentucky, where the point of greatest eclipse occurred. METHODS: EDs flagged visits of patients who participated in eclipse events from August 17-22. Data from 14 area emergency medical services and 26 first-aid stations were also monitored to detect health-related events occurring during the eclipse period. RESULTS: Forty-four potential eclipse event-related visits were identified, primarily injuries, gastrointestinal illness, and heat-related illness. First-aid stations and emergency medical services commonly attended to patients with pain and heat-related illness. CONCLUSIONS: Kentucky's experience during the eclipse demonstrated the value of patient visit flagging to describe the disease burden during a mass gathering and to investigate epidemiological links between cases. A close collaboration between public health authorities within and across jurisdictions, health information exchanges, hospitals, and other first-response care providers will optimize health surveillance activities before, during, and after mass gatherings. |
Population Structure and Genetic Diversity among Isolates of Coccidioides posadasii in Venezuela and Surrounding Regions.
Teixeira MM , Alvarado P , Roe CC , Thompson GR 3rd , Patane JSL , Sahl JW , Keim P , Galgiani JN , Litvintseva AP , Matute DR , Barker BM . mBio 2019 10 (6) Coccidioides posadasii is a pathogenic fungus that causes coccidioidomycosis in many arid regions of the Americas. One of these regions is bordered by the Caribbean Sea, and the surrounding landscape may play an important role in the dispersion of C. posadasii across South America through southeastern Mexico, Honduras, Guatemala, and Venezuela. Comparative phylogenomic analyses of C. posadasii reveal that clinical strains from Venezuela are genetically distinct from the North American populations found in (i) Arizona and (ii) Texas, Mexico, and the rest of South America (TX/MX/SA). We find evidence for admixture between the Venezuela and the North American populations of C. posadasii in Central America. Additionally, the proportion of Venezuelan alleles in the admixed population decreases as latitude (and distance from Venezuela) increases. Our results indicate that the population in Venezuela may have been subjected to a recent bottleneck and shows a strong population structure. This analysis provides insight into potential for Coccidioides spp. to invade new regions.IMPORTANCE Valley Fever is a fungal disease caused by two species of fungi: Coccidioides immitis and C. posadasii These fungi are found throughout the arid regions of North and South America; however, our understanding of genetic diversity and disease in South America is limited. In this report, we analyze 10 new genomes of Coccidioides posadasii from regions bordering the Caribbean Sea. We show that these populations are distinct and that isolates from Venezuela are likely a result of a recent bottleneck. These data point to patterns that might be observed when investigating recently established populations. |
HIV prevention via mobile messaging for men who have sex with men (M-Cubed): Protocol for a randomized controlled trial
Sullivan PS , Zahn RJ , Wiatrek S , Chandler CJ , Hirshfield S , Stephenson R , Bauermeister JA , Chiasson MA , Downing MJJr , Gelaude DJ , Siegler AJ , Horvath K , Rogers E , Alas A , Olansky EJ , Saul H , Rosenberg ES , Mansergh G . JMIR Res Protoc 2019 8 (11) e16439 BACKGROUND: Men who have sex with men (MSM) continue to be the predominately impacted risk group in the United States HIV epidemic and are a priority group for risk reduction in national strategic goals for HIV prevention. Modeling studies have demonstrated that a comprehensive package of status-tailored HIV prevention and care interventions have the potential to substantially reduce new infections among MSM. However, uptake of basic prevention services, including HIV testing, sexually transmitted infection (STI) testing, condom distribution, condom-compatible lubricant distribution, and preexposure prophylaxis (PrEP), is suboptimal. Further, stronger public health strategies are needed to promote engagement in HIV care and viral load suppression among MSM living with HIV. Mobile health (mHealth) tools can help inform and encourage MSM regarding HIV prevention, care, and treatment, especially among men who lack access to conventional medical services. This protocol details the design and procedures of a randomized controlled trial (RCT) of a novel mHealth intervention that comprises a comprehensive HIV prevention app and brief, tailored text- and video-based messages that are systematically presented to participants based on the participants' HIV status and level of HIV acquisition risk. OBJECTIVE: The objective of the RCT was to test the efficacy of the Mobile Messaging for Men (M-Cubed, or M3) app among at least 1200 MSM in Atlanta, Detroit, and New York. The goal was to determine its ability to increase HIV testing (HIV-negative men), STI testing (all men), condom use for anal sex (all men), evaluation for PrEP eligibility, uptake of PrEP (higher risk HIV-negative men), engagement in HIV care (men living with HIV), and uptake of and adherence to antiretroviral medications (men living with HIV). A unique benefit of this approach is the HIV serostatus-inclusiveness of the intervention, which includes both HIV-negative and HIV-positive MSM. METHODS: MSM were recruited through online and venue-based approaches in Atlanta, Detroit, and New York City. Men who were eligible and consented were randomized to the intervention (immediate access to the M3 app for a period of three months) or to the waitlist-control (delayed access) group. Outcomes were evaluated immediately postintervention or control period, and again three and six months after the intervention period. Main outcomes will be reported as period prevalence ratios or hazards, depending on the outcome. Where appropriate, serostatus/risk-specific outcomes will be evaluated in relevant subgroups. Men randomized to the control condition were offered the opportunity to use (and evaluate) the M3 app for a three-month period after the final RCT outcome assessment. RESULTS: M3 enrollment began in January 2018 and concluded in November 2018. A total of 1229 MSM were enrolled. Data collection was completed in September 2019. CONCLUSIONS: This RCT of the M3 mobile app seeks to determine the effects of an HIV serostatus-inclusive intervention on the use of multiple HIV prevention and care-related outcomes among MSM. A strength of the design is that it incorporates a large sample and broad range of MSM with differing prevention needs in three cities with high prevalence of HIV among MSM. TRIAL REGISTRATION: ClinicalTrials.gov NCT03666247; https://clinicaltrials.gov/ct2/show/NCT03666247. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/16439. |
Burkholderia pseudomallei, the causative agent of melioidosis, is rare but ecologically established and widely dispersed in the environment in Puerto Rico.
Hall CM , Jaramillo S , Jimenez R , Stone NE , Centner H , Busch JD , Bratsch N , Roe CC , Gee JE , Hoffmaster AR , Rivera-Garcia S , Soltero F , Ryff K , Perez-Padilla J , Keim P , Sahl JW , Wagner DM . PLoS Negl Trop Dis 2019 13 (9) e0007727 BACKGROUND: Burkholderia pseudomallei is a soil-dwelling bacterium and the causative agent of melioidosis. The global burden and distribution of melioidosis is poorly understood, including in the Caribbean. B. pseudomallei was previously isolated from humans and soil in eastern Puerto Rico but the abundance and distribution of B. pseudomallei in Puerto Rico as a whole has not been thoroughly investigated. METHODOLOGY/PRINCIPAL FINDINGS: We collected 600 environmental samples (500 soil and 100 water) from 60 sites around Puerto Rico. We identified B. pseudomallei by isolating it via culturing and/or using PCR to detect its DNA within complex DNA extracts. Only three adjacent soil samples from one site were positive for B. pseudomallei with PCR; we obtained 55 isolates from two of these samples. The 55 B. pseudomallei isolates exhibited fine-scale variation in the core genome and contained four novel genomic islands. Phylogenetic analyses grouped Puerto Rico B. pseudomallei isolates into a monophyletic clade containing other Caribbean isolates, which was nested inside a larger clade containing all isolates from Central/South America. Other Burkholderia species were commonly observed in Puerto Rico; we cultured 129 isolates from multiple soil and water samples collected at numerous sites around Puerto Rico, including representatives of B. anthina, B. cenocepacia, B. cepacia, B. contaminans, B. glumae, B. seminalis, B. stagnalis, B. ubonensis, and several unidentified novel Burkholderia spp. CONCLUSIONS/SIGNIFICANCE: B. pseudomallei was only detected in three soil samples collected at one site in north central Puerto Rico with only two of those samples yielding isolates. All previous human and environmental B. pseudomallei isolates were obtained from eastern Puerto Rico. These findings suggest B. pseudomallei is ecologically established and widely dispersed in the environment in Puerto Rico but rare. Phylogeographic patterns suggest the source of B. pseudomallei populations in Puerto Rico and elsewhere in the Caribbean may have been Central or South America. |
Update on the Epidemiology of coccidioidomycosis in the United States.
McCotter OZ , Benedict K , Engelthaler DM , Komatsu K , Lucas KD , Mohle-Boetani JC , Oltean H , Vugia D , Chiller TM , Sondermeyer Cooksey GL , Nguyen A , Roe CC , Wheeler C , Sunenshine R . Med Mycol 2019 57 S30-s40 The incidence of reported coccidioidomycosis in the past two decades has increased greatly; monitoring its changing epidemiology is essential for understanding its burden on patients and the healthcare system and for identifying opportunities for prevention and education. We provide an update on recent coccidioidomycosis trends and public health efforts nationally and in Arizona, California, and Washington State. In Arizona, enhanced surveillance shows that coccidioidomycosis continues to be associated with substantial morbidity. California reported its highest yearly number of cases ever in 2016 and has implemented interventions to reduce coccidioidomycosis in the prison population by excluding certain inmates from residing in prisons in high-risk areas. Coccidioidomycosis is emerging in Washington State, where phylogenetic analyses confirm the existence of a unique Coccidioides clade. Additional studies of the molecular epidemiology of Coccidioides will improve understanding its expanding endemic range. Ongoing public health collaborations and future research priorities are focused on characterizing geographic risk, particularly in the context of environmental change; identifying further risk reduction strategies for high-risk groups; and improving reporting of cases to public health agencies. |
Zoonotic Source Attribution of Salmonella enterica Serotype Typhimurium Using Genomic Surveillance Data, United States.
Zhang S , Li S , Gu W , den Bakker H , Boxrud D , Taylor A , Roe C , Driebe E , Engelthaler DM , Allard M , Brown E , McDermott P , Zhao S , Bruce BB , Trees E , Fields PI , Deng X . Emerg Infect Dis 2019 25 (1) 82-91 Increasingly, routine surveillance and monitoring of foodborne pathogens using whole-genome sequencing is creating opportunities to study foodborne illness epidemiology beyond routine outbreak investigations and case-control studies. Using a global phylogeny of Salmonella enterica serotype Typhimurium, we found that major livestock sources of the pathogen in the United States can be predicted through whole-genome sequencing data. Relatively steady rates of sequence divergence in livestock lineages enabled the inference of their recent origins. Elevated accumulation of lineage-specific pseudogenes after divergence from generalist populations and possible metabolic acclimation in a representative swine isolate indicates possible emergence of host adaptation. We developed and retrospectively applied a machine learning Random Forest classifier for genomic source prediction of Salmonella Typhimurium that correctly attributed 7 of 8 major zoonotic outbreaks in the United States during 1998-2013. We further identified 50 key genetic features that were sufficient for robust livestock source prediction. |
Utility of Whole-Genome Sequencing to Ascertain Locally Acquired Cases of Coccidioidomycosis, Washington, USA.
Oltean HN , Etienne KA , Roe CC , Gade L , McCotter OZ , Engelthaler DM , Litvintseva AP . Emerg Infect Dis 2019 25 (3) 501-506 Coccidioidomycosis is an emerging fungal infection in Washington, USA, and the epidemiology of the disease in this state is poorly understood. We used whole-genome sequencing to differentiate locally acquired cases in Washington on the basis of the previously identified phylogeographic population structure of Coccidioides spp. Clinical isolates from coccidioidomycosis cases involving possible Washington soil exposure were included. Of 17 human infections with epidemiologic evidence of possible local acquisition, 4 were likely locally acquired infections and 13 were likely acquired outside Washington. Isolates from locally acquired cases clustered within the previously established Washington clade of C. immitis. Genetic differences among these strains suggest multiple environmental reservoirs of C. immitis in the state. |
Impact of abstinence and of reducing illicit drug use without abstinence on HIV viral load
Nance RM , Trejo MEP , Whitney BM , Delaney JAC , Altice F , Beckwith CG , Chander G , Chandler R , Christopoulous K , Cunningham C , Cunningham WE , Del Rio C , Donovan D , Eron JJ , Fredericksen RJ , Kahana S , Kitahata MM , Kronmal R , Kuo I , Kurth A , Mathews WC , Mayer KH , Moore RD , Mugavero MJ , Ouellet LJ , Quan VM , Saag MS , Simoni JM , Springer S , Strand L , Taxman F , Young JD , Crane HM . Clin Infect Dis 2019 70 (5) 867-874 BACKGROUND: Substance use is common among people living with HIV (PLWH) and a barrier to achieving viral suppression. OBJECTIVE: Among PLWH who report illicit drug use, we evaluated associations between HIV viral load (VL) and reduced use of illicit opioids, methamphetamine/crystal, cocaine/crack, and marijuana, regardless of whether or not abstinence was achieved. DESIGN: Longitudinal cohort studySetting/participantsPLWH in clinical care at 8 HIV clinics or 5 clinical studies. MEASUREMENTS: We used joint longitudinal and survival models to examine the impact of decreasing drug use and of abstinence for each drug on viral suppression. We repeated analyses using linear mixed models to examine associations between change in frequency of drug use and VL. RESULTS: The number of PLWH who were using each drug at baseline ranged from n=568 (illicit opioids) to n=4272 (marijuana). Abstinence was associated with higher odds of viral suppression (OR 1.4-2.2) and lower relative VL (ranging from 21-42% by drug) for all four drug categories. Reducing frequency of illicit opioid or methamphetamine/crystal use without abstinence was associated with VL suppression (OR 2.2, 1.6 respectively). Reducing frequency of illicit opioid or methamphetamine/crystal use without abstinence was associated with lower relative VL (47%, 38% respectively). LIMITATIONS: Observational data have limitations with causal inference. CONCLUSIONS: Abstinence was associated with viral suppression. In addition, reducing use of illicit opioids or methamphetamine/crystal, even without abstinence, was also associated with viral suppression. Findings highlight the impact of reducing substance use even when abstinence is not achieved and the potential benefits of medications, behavioral interventions, and harm-reduction interventions. |
Timing the Origin of Cryptococcus gattii sensu stricto, Southeastern United States.
Lockhart SR , Roe CC , Engelthaler DM . Emerg Infect Dis 2018 24 (11) 2095-2097 We conducted molecular clock analysis of whole-genome sequences from a set of autochthonous isolates of Cryptococcus gattii sensu stricto from the southeastern United States. Our analysis indicates that C. gattii arrived in the southeastern United States approximately 9,000-19,000 years ago, long before its arrival in the Pacific Northwest. |
Improved Subtyping of Staphylococcus aureus Clonal Complex 8 Strains Based on Whole-Genome Phylogenetic Analysis.
Bowers JR , Driebe EM , Albrecht V , McDougal LK , Granade M , Roe CC , Lemmer D , Rasheed JK , Engelthaler DM , Keim P , Limbago BM . mSphere 2018 3 (3) Strains of Staphylococcus aureus in clonal complex 8 (CC8), including USA300, USA500, and the Iberian clone, are prevalent pathogens in the United States, both inside and outside health care settings. Methods for typing CC8 strains are becoming obsolete as the strains evolve and diversify, and whole-genome sequencing has shown that some strain types fall into multiple sublineages within CC8. In this study, we attempt to clarify the strain nomenclature of CC8, classifying the major strain types based on whole-genome sequence phylogenetics using both methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) genomes. We show that isolates of the Archaic and Iberian clones from decades ago make up the most basal clade of the main CC8 lineages and that at least one successful lineage of CC8, made up mostly of MSSA, diverged before the other well-known strain types USA500 and USA300. We also show that the USA500 type includes two clades separated by the previously described "Canadian epidemic MRSA" strain CMRSA9, that one clade containing USA500 also contains the USA300 clade, and that the USA300-0114 strain type is not a monophyletic group. Additionally, we present a rapid, simple CC8 strain-typing scheme using real-time PCR assays that target single nucleotide polymorphisms (SNPs) derived from our CC8 phylogeny and show the significant benefit of using more stable genomic markers based on evolutionary lineages over traditional S. aureus typing techniques. This more accurate and accessible S. aureus typing system may improve surveillance and better inform the epidemiology of this very important pathogen.IMPORTANCEStaphylococcus aureus is a major human pathogen worldwide in both community and health care settings. Surveillance for S. aureus strains is important to our understanding of their spread and to informing infection prevention and control. Confusion surrounding the strain nomenclature of one of the most prevalent lineages of S. aureus, clonal complex 8 (CC8), and the imprecision of current tools for typing S. aureus make surveillance and source tracing difficult and sometimes misleading. In this study, we clarify the CC8 strain designations and propose a new typing scheme for CC8 isolates that is rapid and easy to use. This typing scheme is based on relatively stable genomic markers, and we demonstrate its superiority over traditional typing techniques. This scheme has the potential to greatly improve epidemiological investigations of S. aureus. |
A bead-based flow cytometric assay for monitoring Yersinia pestis exposure in wildlife
Chandler JC , Baeten LA , Griffin DL , Gidlewski T , DeLiberto TJ , Petersen JM , Pappert R , Young JW , Bevins SN . J Clin Microbiol 2018 56 (7) Yersinia pestis is the causative agent of plague, and is considered a category A priority pathogen due to its potential for high transmissibility and the significant morbidity and mortality it causes in humans. Y. pestis is endemic to the Western United States and much of the world, necessitating programs to monitor for this pathogen on the landscape. Elevated human risk of plague infection has been spatially correlated with spikes in seropositive wildlife numbers, particularly rodent-eating carnivores which are frequently in contact with the enzootic hosts and the associated arthropod vectors of Y. pestis In this study, we describe a semi-automated bead-based flow cytometric assay developed for plague monitoring in wildlife called the F1-Luminex Plague Assay (F1-LPA). Based upon Luminex/Bio-Plex technology, the F1-LPA targets serological responses to the F1 capsular antigen of Y. pestis and was optimized to analyze antibodies eluted from wildlife blood samples preserved on Nobuto filter paper strips. In comparative evaluations using wildlife samples with passive hemagglutination, the gold standard tool for wildlife plague serodiagnosis, the F1-LPA demonstrated as much as 64x improvement in analytical sensitivity to F1-specific IgG detection, and allowed for unambiguous classification of IgG status. The functionality of the F1-LPA was demonstrated for coyotes and other canids, which are the primary sentinels in wildlife plague monitoring, as well as felids and raccoons. Additionally, assay formats that do not require species-specific immunological reagents, which are not routinely available for several wildlife species used in plague monitoring, were determined to be functional in the F1-LPA. |
Public health resilience checklist for high-consequence infectious diseases-informed by the domestic Ebola response in the United States
Sell TK , Shearer MP , Meyer D , Chandler H , Schoch-Spana M , Thomas E , Rose DA , Carbone EG , Toner E . J Public Health Manag Pract 2018 24 (6) 510-518 CONTEXT: The experiences of communities that responded to confirmed cases of Ebola virus disease in the United States provide a rare opportunity for collective learning to improve resilience to future high-consequence infectious disease events. DESIGN: Key informant interviews (n = 73) were conducted between February and November 2016 with individuals who participated in Ebola virus disease planning or response in Atlanta, Georgia; Dallas, Texas; New York, New York; or Omaha, Nebraska; or had direct knowledge of response activities. Participants represented health care; local, state, and federal public health; law; local and state emergency management; academia; local and national media; individuals affected by the response; and local and state governments. Two focus groups were then conducted in New York and Dallas, and study results were vetted with an expert advisory group. RESULTS: Participants focused on a number of important areas to improve public health resilience to high-consequence infectious disease events, including governance and leadership, communication and public trust, quarantine and the law, monitoring programs, environmental decontamination, and waste management. CONCLUSIONS: Findings provided the basis for an evidence-informed checklist outlining specific actions for public health authorities to take to strengthen public health resilience to future high-consequence infectious disease events. |
A longitudinal study of estrogen-responsive tissues and hormone concentrations in infants fed soy formula
Adgent MA , Umbach DM , Zemel BS , Kelly A , Schall JI , Ford EG , James K , Darge K , Botelho JC , Vesper HW , Chandler DW , Nakamoto JM , Rogan WJ , Stallings VA . J Clin Endocrinol Metab 2018 103 (5) 1899-1909 Purpose: Chemicals with hormone-like activity, such as estrogenic isoflavones, may perturb human development. Infants exclusively fed soy-based formula are highly exposed to isoflavones, but their physiologic responses remain uncharacterized. Here, we compare estrogen-responsive postnatal development in infants exclusively fed soy formula, cow-milk formula and breast milk. Methods: We enrolled 410 infants born in Philadelphia area hospitals, 2010-2013; 283 infants were exclusively fed soy formula (n=102), cow-milk formula (n=111), or breast milk (n=70) throughout the study (birth to 28 [boys] or 36 [girls] weeks). We repeatedly measured maturation index (MI) in vaginal and urethral epithelial cells using standard cytological methods, uterine volume and breast-bud diameter using ultrasound, serum estradiol and, in girls, follicle-stimulating hormone. We estimated MI, organ-growth and hormone trajectories by diet using mixed-effects regression splines. Results: Maternal demographics did not differ between cow-milk-fed and soy-fed infants but did differ between formula-fed and breastfed infants. Vaginal cell MI trended higher (p=0.01) and uterine volume decreased more slowly (p=0.01) in soy-fed girls compared to cow-milk-fed girls; however, their trajectories of breast-bud diameter and hormone concentrations did not differ. We observed no significant differences between boys fed cow-milk formula versus soy formula; estradiol was not detectable. Breastfed infants differed from soy-formula-fed infants in vaginal cell MI, uterine volume, girls' estradiol and boys' breast-bud diameter trajectories. Conclusions: Relative to cow-milk formula-fed girls, soy formula-fed girls demonstrated tissue and organ-level developmental trajectories consistent with response to exogenous estrogen exposure. Additional studies are needed to further evaluate the effects of soy on child development. |
Dating the Cryptococcus gattii Dispersal to the North American Pacific Northwest.
Roe CC , Bowers J , Oltean H , DeBess E , Dufresne PJ , McBurney S , Overy DP , Wanke B , Lysen C , Chiller T , Meyer W , Thompson GR3rd , Lockhart SR , Hepp CM , Engelthaler DM . mSphere 2018 3 (1) The emergence of Cryptococcus gattii, previously regarded as a predominantly tropical pathogen, in the temperate climate of the North American Pacific Northwest (PNW) in 1999 prompted several questions. The most prevalent among these was the timing of the introduction of this pathogen to this novel environment. Here, we infer tip-dated timing estimates for the three clonal C. gattii populations observed in the PNW, VGIIa, VGIIb, and VGIIc, based on whole-genome sequencing of 134 C. gattii isolates and using Bayesian evolutionary analysis by sampling trees (BEAST). We estimated the nucleotide substitution rate for each lineage (1.59 x 10(-8), 1.59 x 10(-8), and 2.70 x 10(-8), respectively) to be an order of magnitude higher than common neutral fungal mutation rates (2.0 x 10(-9)), indicating a microevolutionary rate (e.g., successive clonal generations in a laboratory) in comparison to a species' slower, macroevolutionary rate (e.g., when using fossil records). The clonal nature of the PNW C. gattii emergence over a narrow number of years would therefore possibly explain our higher mutation rates. Our results suggest that the mean time to most recent common ancestor for all three sublineages occurred within the last 60 to 100 years. While the cause of C. gattii dispersal to the PNW is still unclear, our research estimates that the arrival is neither ancient nor very recent (i.e., <25 years ago), making a strong case for an anthropogenic introduction. IMPORTANCE The recent emergence of the pathogenic fungus Cryptococcus gattii in the Pacific Northwest (PNW) resulted in numerous investigations into the epidemiological and enzootic impacts, as well as multiple genomic explorations of the three primary molecular subtypes of the fungus that were discovered. These studies lead to the general conclusion that the subtypes identified likely emerged out of Brazil. Here, we conducted genomic dating analyses to determine the ages of the various lineages seen in the PNW and propose hypothetical causes for the dispersal events. Bayesian evolutionary analysis strongly suggests that these independent fungal populations in the PNW are all 60 to 100 years old, providing a timing that is subsequent to the opening of the Panama Canal, which allowed for more direct shipping between Brazil and the western North American coastline, a possible driving event for these fungal translocation events. |
Lessons from the domestic Ebola response: Improving health care system resilience to high consequence infectious diseases
Meyer D , Kirk Sell T , Schoch-Spana M , Shearer MP , Chandler H , Thomas E , Rose DA , Carbone EG , Toner E . Am J Infect Control 2017 46 (5) 533-537 BACKGROUND: The domestic response to the West Africa Ebola virus disease (EVD) epidemic from 2014-2016 provides a unique opportunity to distill lessons learned about health sector planning and operations from those individuals directly involved. This research project aimed to identify and integrate these lessons into an actionable checklist that can improve health sector resilience to future high-consequence infectious disease (HCID) events. METHODS: Interviews (N = 73) were completed with individuals involved in the domestic EVD response in 4 cities (Atlanta, Dallas, New York, and Omaha), and included individuals who worked in academia, emergency management, government, health care, law, media, and public health during the response. Interviews were transcribed and analyzed qualitatively. Two focus groups were then conducted to expand on themes identified in the interviews. Using these themes, an evidence-informed checklist was developed and vetted for completeness and feasibility by an expert advisory group. RESULTS: Salient themes identified included health care facility issues-specifically identifying assessment and treatment hospitals, isolation and treatment unit layout, waste management, community relations, patient identification, patient isolation, limitations on treatment, laboratories, and research considerations-and health care workforce issues-specifically psychosocial impact, unit staffing, staff training, and proper personal protective equipment. CONCLUSIONS: The experiences of those involved in the domestic Ebola response provide critical lessons that can help strengthen resilience of health care systems and improve future responses to HCID events. |
The impact of introducing malaria rapid diagnostic tests on fever case management: A synthesis of ten studies from the ACT Consortium
Bruxvoort KJ , Leurent B , Chandler CIR , Ansah EK , Baiden F , Bjorkman A , Burchett HED , Clarke SE , Cundill B , DiLiberto DD , Elfving K , Goodman C , Hansen KS , Kachur SP , Lal S , Lalloo DG , Leslie T , Magnussen P , Mangham-Jefferies L , Martensson A , Mayan I , Mbonye AK , Msellem MI , Onwujekwe OE , Owusu-Agyei S , Rowland MW , Shakely D , Staedke SG , Vestergaard LS , Webster J , Whitty CJM , Wiseman VL , Yeung S , Schellenberg D , Hopkins H . Am J Trop Med Hyg 2017 97 (4) 1170-1179 Since 2010, the World Health Organization has been recommending that all suspected cases of malaria be confirmed with parasite-based diagnosis before treatment. These guidelines represent a paradigm shift away from presumptive antimalarial treatment of fever. Malaria rapid diagnostic tests (mRDTs) are central to implementing this policy, intended to target artemisinin-based combination therapies (ACT) to patients with confirmed malaria and to improve management of patients with nonmalarial fevers. The ACT Consortium conducted ten linked studies, eight in sub-Saharan Africa and two in Afghanistan, to evaluate the impact of mRDT introduction on case management across settings that vary in malaria endemicity and healthcare provider type. This synthesis includes 562,368 outpatient encounters (study size range 2,400-432,513). mRDTs were associated with significantly lower ACT prescription (range 8-69% versus 20-100%). Prescribing did not always adhere to malaria test results; in several settings, ACTs were prescribed to more than 30% of test-negative patients or to fewer than 80% of test-positive patients. Either an antimalarial or an antibiotic was prescribed for more than 75% of patients across most settings; lower antimalarial prescription for malaria test-negative patients was partly offset by higher antibiotic prescription. Symptomatic management with antipyretics alone was prescribed for fewer than 25% of patients across all scenarios. In community health worker and private retailer settings, mRDTs increased referral of patients to other providers. This synthesis provides an overview of shifts in case management that may be expected with mRDT introduction and highlights areas of focus to improve design and implementation of future case management programs. |
Impact of introduction of rapid diagnostic tests for malaria on antibiotic prescribing: analysis of observational and randomised studies in public and private healthcare settings
Hopkins H , Bruxvoort KJ , Cairns ME , Chandler CI , Leurent B , Ansah EK , Baiden F , Baltzell KA , Bjorkman A , Burchett HE , Clarke SE , DiLiberto DD , Elfving K , Goodman C , Hansen KS , Kachur SP , Lal S , Lalloo DG , Leslie T , Magnussen P , Jefferies LM , Mårtensson A , Mayan I , Mbonye AK , Msellem MI , Onwujekwe OE , Owusu-Agyei S , Reyburn H , Rowland MW , Shakely D , Vestergaard LS , Webster J , Wiseman VL , Yeung S , Schellenberg D , Staedke SG , Whitty CJ . BMJ 2017 356 j1054 Objectives To examine the impact of use of rapid diagnostic tests for malaria on prescribing of antimicrobials, specifically antibiotics, for acute febrile illness in Africa and Asia.Design Analysisof nine preselected linked and codesigned observational and randomised studies (eight cluster or individually randomised trials and one observational study).Setting Public and private healthcare settings, 2007-13, in Afghanistan, Cameroon, Ghana, Nigeria, Tanzania, and Uganda.Participants 522 480 children and adults with acute febrile illness.Interventions Rapid diagnostic tests for malaria.Main outcome measures Proportions of patients for whom an antibiotic was prescribed in trial groups who had undergone rapid diagnostic testing compared with controls and in patients with negative test results compared with patients with positive results. A secondary aim compared classes of antibiotics prescribed in different settings.Results Antibiotics were prescribed to 127 052/238 797 (53%) patients in control groups and 167 714/283 683 (59%) patients in intervention groups. Antibiotics were prescribed to 40% (35 505/89 719) of patients with a positive test result for malaria and to 69% (39 400/57 080) of those with a negative result. All but one study showed a trend toward more antibiotic prescribing in groups who underwent rapid diagnostic tests. Random effects meta-analysis of the trials showed that the overall risk of antibiotic prescription was 21% higher (95% confidence interval 7% to 36%) in intervention settings. In most intervention settings, patients with negative test results received more antibiotic prescriptions than patients with positive results for all the most commonly used classes: penicillins, trimethoprim-sulfamethoxazole (one exception), tetracyclines, and metronidazole.Conclusions Introduction of rapid diagnostic tests for malaria to reduce unnecessary use of antimalarials-a beneficial public health outcome-could drive up untargeted use of antibiotics. That 69% of patients were prescribed antibiotics when test results were negative probably represents overprescription.This included antibiotics from several classes, including those like metronidazole that are seldom appropriate for febrile illness, across varied clinical, health system, and epidemiological settings. It is often assumed that better disease specific diagnostics will reduce antimicrobial overuse, but they might simply shift it from one antimicrobial class to another. Current global implementation of malaria testing might increase untargeted antibiotic use and must be examined. |
Improving prescribing practices with rapid diagnostic tests (RDTs): synthesis of 10 studies to explore reasons for variation in malaria RDT uptake and adherence
Burchett HE , Leurent B , Baiden F , Baltzell K , Bjorkman A , Bruxvoort K , Clarke S , DiLiberto D , Elfving K , Goodman C , Hopkins H , Lal S , Liverani M , Magnussen P , Martensson A , Mbacham W , Mbonye A , Onwujekwe O , Roth Allen D , Shakely D , Staedke S , Vestergaard LS , Whitty CJ , Wiseman V , Chandler CI . BMJ Open 2017 7 (3) e012973 OBJECTIVES: The overuse of antimalarial drugs is widespread. Effective methods to improve prescribing practice remain unclear. We evaluated the impact of 10 interventions that introduced rapid diagnostic tests for malaria (mRDTs) on the use of tests and adherence to results in different contexts. DESIGN: A comparative case study approach, analysing variation in outcomes across different settings. SETTING: Studies from the ACT Consortium evaluating mRDTs with a range of supporting interventions in 6 malaria endemic countries. Providers were governmental or non-governmental healthcare workers, private retail sector workers or community volunteers. Each study arm in a distinct setting was considered a case. PARTICIPANTS: 28 cases from 10 studies were included, representing 148 461 patients seeking care for suspected malaria. INTERVENTIONS: The interventions included different mRDT training packages, supervision, supplies and community sensitisation. OUTCOME MEASURES: Analysis explored variation in: (1) uptake of mRDTs (% febrile patients tested); (2) provider adherence to positive mRDTs (% Plasmodium falciparum positive prescribed/given Artemisinin Combination Treatment); (3) provider adherence to negative mRDTs (% P. falciparum negative not prescribed/given antimalarial). RESULTS: Outcomes varied widely across cases: 12-100% mRDT uptake; 44-98% adherence to positive mRDTs; 27-100% adherence to negative mRDTs. Providers appeared more motivated to perform well when mRDTs and intervention characteristics fitted with their own priorities. Goodness of fit of mRDTs with existing consultation and diagnostic practices appeared crucial to maximising the impact of mRDTs on care, as did prior familiarity with malaria testing; adequate human resources and supplies; possible alternative treatments for mRDT-negative patients; a more directive intervention approach and local preferences for ACTs. CONCLUSIONS: Basic training and resources are essential but insufficient to maximise the potential of mRDTs in many contexts. Programme design should respond to assessments of provider priorities, expectations and capacities. As mRDTs become established, the intensity of supporting interventions required seems likely to reduce. |
Integrating health into buildings of the future
Heidari L , Younger M , Chandler G , Gooch J , Schramm P . J Sol Energy Eng 2017 139 (1) 010802 The health and wellbeing of building occupants should be a key priority in the design, building, and operation of new and existing buildings. Buildings can be designed, renovated, and constructed to promote healthy environments and behaviors and mitigate adverse health outcomes. This paper highlights health in terms of the relationship between occupants and buildings, as well as the relationship of buildings to the community. In the context of larger systems, smart buildings and green infrastructure strategies serve to support public health goals. At the level of the individual building, interventions that promote health can also enhance indoor environmental quality (IEQ) and provide opportunities for physical activity. Navigating the various programs that use metrics to measure a building's health impacts reveals that there are multiple co-benefits of a "healthy building," including those related to the economy, environment, society, transportation, planning, and energy efficiency. |
MLST and Whole-Genome-Based Population Analysis of Cryptococcus gattii VGIII Links Clinical, Veterinary and Environmental Strains, and Reveals Divergent Serotype Specific Sub-populations and Distant Ancestors.
Firacative C , Roe CC , Malik R , Ferreira-Paim K , Escandon P , Sykes JE , Castanon-Olivares LR , Contreras-Peres C , Samayoa B , Sorrell TC , Castaneda E , Lockhart SR , Engelthaler DM , Meyer W . PLoS Negl Trop Dis 2016 10 (8) e0004861 The emerging pathogen Cryptococcus gattii causes life-threatening disease in immunocompetent and immunocompromised hosts. Of the four major molecular types (VGI-VGIV), the molecular type VGIII has recently emerged as cause of disease in otherwise healthy individuals, prompting a need to investigate its population genetic structure to understand if there are potential genotype-dependent characteristics in its epidemiology, environmental niche(s), host range and clinical features of disease. Multilocus sequence typing (MLST) of 122 clinical, environmental and veterinary C. gattii VGIII isolates from Australia, Colombia, Guatemala, Mexico, New Zealand, Paraguay, USA and Venezuela, and whole genome sequencing (WGS) of 60 isolates representing all established MLST types identified four divergent sub-populations. The majority of the isolates belong to two main clades, corresponding either to serotype B or C, indicating an ongoing species evolution. Both major clades included clinical, environmental and veterinary isolates. The C. gattii VGIII population was genetically highly diverse, with minor differences between countries, isolation source, serotype and mating type. Little to no recombination was found between the two major groups, serotype B and C, at the whole and mitochondrial genome level. C. gattii VGIII is widespread in the Americas, with sporadic cases occurring elsewhere, WGS revealed Mexico and USA as a likely origin of the serotype B VGIII population and Colombia as a possible origin of the serotype C VGIII population. Serotype B isolates are more virulent than serotype C isolates in a murine model of infection, causing predominantly pulmonary cryptococcosis. No specific link between genotype and virulence was observed. Antifungal susceptibility testing against six antifungal drugs revealed that serotype B isolates are more susceptible to azoles than serotype C isolates, highlighting the importance of strain typing to guide effective treatment to improve the disease outcome. |
Whole-Genome Analysis of Cryptococcus gattii, Southeastern United States.
Lockhart SR , Roe CC , Engelthaler DM . Emerg Infect Dis 2016 22 (6) 1098-101 Cryptococcus gattii is a recognized pathogenic fungus along the Pacific coast of the United States from California to Washington. Here we report that C. gattii may also be endemic to the southeastern United States and has probably been present there longer than in the Pacific Northwest. |
Local Population Structure and Patterns of Western Hemisphere Dispersal for Coccidioides spp., the Fungal Cause of Valley Fever.
Engelthaler DM , Roe CC , Hepp CM , Teixeira M , Driebe EM , Schupp JM , Gade L , Waddell V , Komatsu K , Arathoon E , Logemann H , Thompson GR 3rd , Chiller T , Barker B , Keim P , Litvintseva AP . mBio 2016 7 (2) e00550-16 Coccidioidomycosis (or valley fever) is a fungal disease with high morbidity and mortality that affects tens of thousands of people each year. This infection is caused by two sibling species, Coccidioides immitis and C. posadasii, which are endemic to specific arid locales throughout the Western Hemisphere, particularly the desert southwest of the United States. Recent epidemiological and population genetic data suggest that the geographic range of coccidioidomycosis is expanding, as new endemic clusters have been identified in the state of Washington, well outside the established endemic range. The genetic mechanisms and epidemiological consequences of this expansion are unknown and require better understanding of the population structure and evolutionary history of these pathogens. Here we performed multiple phylogenetic inference and population genomics analyses of 68 new and 18 previously published genomes. The results provide evidence of substantial population structure in C. posadasii and demonstrate the presence of distinct geographic clades in central and southern Arizona as well as dispersed populations in Texas, Mexico, South America, and Central America. Although a smaller number of C. immitis strains were included in the analyses, some evidence of phylogeographic structure was also detected in this species, which has been historically limited to California and Baja, Mexico. Bayesian analyses indicated that C. posadasii is the more ancient of the two species and that Arizona contains the most diverse subpopulations. We propose a southern Arizona-northern Mexico origin for C. posadasii and describe a pathway for dispersal and distribution out of this region. IMPORTANCE: Coccidioidomycosis, or valley fever, is caused by the pathogenic fungi Coccidioides posadasii and C. immitis The fungal species and disease are primarily found in the American desert southwest, with spotted distribution throughout the Western Hemisphere. Initial molecular studies suggested a likely anthropogenic movement of C. posadasii from North America to South America. Here we comparatively analyze eighty-six genomes of the two Coccidioides species and establish local and species-wide population structures to not only clarify the earlier dispersal hypothesis but also provide evidence of likely ancestral populations and patterns of dispersal for the known subpopulations of C. posadasii. |
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