Publications by authors named "Charles B Beard"

40 Publications

The Rise of Ticks and Tickborne Diseases in the United States-Introduction.

J Med Entomol 2021 May 3. Epub 2021 May 3.

Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, 3156 Rampart Road, Fort Collins, CO 80521, USA.

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http://dx.doi.org/10.1093/jme/tjab064DOI Listing
May 2021

Epidemiology, Ecology and Prevention of Plague in the West Nile Region of Uganda: The Value of Long-Term Field Studies.

Am J Trop Med Hyg 2021 May 3. Epub 2021 May 3.

1Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado.

Plague, a fleaborne rodent-associated zoonosis, is a neglected disease with most recent cases reported from east and central Africa and Madagascar. Because of its low incidence and sporadic occurrence, most of our knowledge of plague ecology, prevention, and control derives from investigations conducted in response to human cases. Long-term studies (which are uncommon) are required to generate data to support plague surveillance, prevention, and control recommendations. Here we describe a 15-year, multidisciplinary commitment to plague in the West Nile region of Uganda that led to significant advances in our understanding of where and when persons are at risk for plague infection and how to reduce morbidity and mortality. These findings provide data-driven support for several existing recommendations on plague surveillance and prevention and may be generalizable to other plague foci.
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http://dx.doi.org/10.4269/ajtmh.20-1381DOI Listing
May 2021

Under pressure: phenotypic divergence and convergence associated with microhabitat adaptations in Triatominae.

Parasit Vectors 2021 Apr 8;14(1):195. Epub 2021 Apr 8.

Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.

Background: Triatomine bugs, the vectors of Chagas disease, associate with vertebrate hosts in highly diverse ecotopes. It has been proposed that occupation of new microhabitats may trigger selection for distinct phenotypic variants in these blood-sucking bugs. Although understanding phenotypic variation is key to the study of adaptive evolution and central to phenotype-based taxonomy, the drivers of phenotypic change and diversity in triatomines remain poorly understood.

Methods/results: We combined a detailed phenotypic appraisal (including morphology and morphometrics) with mitochondrial cytb and nuclear ITS2 DNA sequence analyses to study Rhodnius ecuadoriensis populations from across the species' range. We found three major, naked-eye phenotypic variants. Southern-Andean bugs primarily from vertebrate-nest microhabitats (Ecuador/Peru) are typical, light-colored, small bugs with short heads/wings. Northern-Andean bugs from wet-forest palms (Ecuador) are dark, large bugs with long heads/wings. Finally, northern-lowland bugs primarily from dry-forest palms (Ecuador) are light-colored and medium-sized. Wing and (size-free) head shapes are similar across Ecuadorian populations, regardless of habitat or phenotype, but distinct in Peruvian bugs. Bayesian phylogenetic and multispecies-coalescent DNA sequence analyses strongly suggest that Ecuadorian and Peruvian populations are two independently evolving lineages, with little within-lineage phylogeographic structuring or differentiation.

Conclusions: We report sharp naked-eye phenotypic divergence of genetically similar Ecuadorian R. ecuadoriensis (nest-dwelling southern-Andean vs palm-dwelling northern bugs; and palm-dwelling Andean vs lowland), and sharp naked-eye phenotypic similarity of typical, yet genetically distinct, southern-Andean bugs primarily from vertebrate-nest (but not palm) microhabitats. This remarkable phenotypic diversity within a single nominal species likely stems from microhabitat adaptations possibly involving predator-driven selection (yielding substrate-matching camouflage coloration) and a shift from palm-crown to vertebrate-nest microhabitats (yielding smaller bodies and shorter and stouter heads). These findings shed new light on the origins of phenotypic diversity in triatomines, warn against excess reliance on phenotype-based triatomine-bug taxonomy, and confirm the Triatominae as an informative model system for the study of phenotypic change under ecological pressure .
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http://dx.doi.org/10.1186/s13071-021-04647-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034103PMC
April 2021

Diagnostic testing for galactose-alpha-1,3-galactose, United States, 2010 to 2018.

Ann Allergy Asthma Immunol 2021 04 7;126(4):411-416.e1. Epub 2021 Jan 7.

Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado.

Background: Alpha-gal syndrome (AGS) is an emerging immunoglobulin E (IgE)-mediated allergy to galactose-alpha-1,3-galactose (alpha-gal). The geographic distribution and burden of AGS in the United States are unknown.

Objective: To characterize alpha-gal IgE testing patterns and describe the trends and distribution from 2010 to 2018 in the United States.

Methods: This retrospective analysis included all persons tested for alpha-gal IgE antibodies by Viracor-IBT Laboratories (Lee's Summit, Missouri), the primary site of testing in the United States. Data included age and sex of person tested, specimen state of origin, collection date, and result value; persons with at least 1 positive test result (≥0.1 kU/L) were compared with negatives. Proportions tested and with positive test results were calculated using the US Census population estimates.

Results: Overall, 122,068 specimens from 105,674 persons were tested for alpha-gal IgE during July 1, 2010, to December 31, 2018. Nearly one-third (34,256, 32.4%) had at least 1 positive result. The number of persons receiving positive test results increased 6-fold from 1110 in 2011 to 7798 in 2018. Of those receiving positive test results, mean [SD] age was 46.9 (19.8) years; men were more likely to test positive than women (43.3% vs 26.0%). Arkansas, Virginia, Kentucky, Oklahoma, and Missouri had the highest number of persons who were tested and had a positive result per 100,000 population.

Conclusion: More than 34,000 persons, most presumably symptomatic, have received positive test results for IgE antibodies to alpha-gal, suggesting AGS is an increasingly recognized public health problem. The geographic distribution of persons who tested positive is consistent with exposure to Amblyomma americanum ticks.
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http://dx.doi.org/10.1016/j.anai.2020.12.019DOI Listing
April 2021

The Need for a National Strategy to Address Vector-Borne Disease Threats in the United States.

J Med Entomol 2019 09;56(5):1199-1203

Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO.

Vector-borne diseases (VBDs) cause significant morbidity and mortality each year in the United States. Over the last 14 yr, over 700,000 cases of diseases carried by ticks, mosquitoes, and fleas have been reported from U.S. states and territories to the Centers for Disease Control and Prevention. The number of reported cases has been increasing annually with two major trends: a steady increase in tick-borne diseases and increasing intermittent outbreaks of mosquito-borne arboviruses. The factors that are driving VBD introduction and emergence vary among diseases but are not likely to disappear, indicating that current trends will continue and probably worsen in the absence of effective prevention and control tools and implementation capacity. There are a number of challenges to preventing VBDs, including the lack of vaccines and effective vector control tools, insecticide resistance, and eroding technical capacities in public health entomology at federal, state, and local levels. For these reasons, a national strategy is needed to address VBD threats and to reverse the alarming trend in morbidity and mortality associated with these diseases.
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http://dx.doi.org/10.1093/jme/tjz074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058377PMC
September 2019

Bioabsorption and effectiveness of long-lasting permethrin-treated uniforms over three months among North Carolina outdoor workers.

Parasit Vectors 2019 Jan 23;12(1):52. Epub 2019 Jan 23.

Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC, USA.

Background: Vector-borne diseases are an important cause of morbidity and mortality in the USA. Effective, convenient prevention methods are needed. Long-lasting permethrin-impregnated (LLPI) clothing can prevent tick bites, however, additional information is needed on the real-world effectiveness and safety of this preventative measure.

Methods: In this pilot study, we recruited state and county park employees from North Carolina to wear LLPI uniforms for three months during the summer of 2016. We collected spot urine samples for biomonitoring of permethrin metabolites at one week, one month and three months after first use of the LLPI uniform. Following three months of wear, we collected pants and socks and analyzed them for permethrin content and mortality to ticks and mosquitoes.

Results: Thirteen park employees were included in the analysis. Bioactive amounts of permethrin remained in all clothing swatches tested, although there was great variability. Tick mortality was high, with 78% of pant and 88% of sock swatches having mean knockdown percentages ≥ 85%. In contrast, mosquito mortality was low. Over the study period, the absorbed dosage of permethrin averaged < 4 μg/kg/d of body weight based on measurements of three metabolites.

Conclusions: LLPI clothing retained permethrin and bioactivity against ticks after three months of use in real-world conditions. The estimated absorbed dosage of permethrin was well below the U.S. EPA level of concern, suggesting that LLPI clothing can be used safely by outdoor workers for tick bite prevention.
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http://dx.doi.org/10.1186/s13071-019-3314-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343280PMC
January 2019

Combatting the Increasing Threat of Vector-Borne Disease in the United States with a National Vector-Borne Disease Prevention and Control System.

Am J Trop Med Hyg 2019 02;100(2):242-245

Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado.

Reported cases of vector-borne diseases in the United States have more than tripled since 2004, characterized by steadily increasing incidence of tick-borne diseases and sporadic outbreaks of domestic and invasive mosquito-borne diseases. An effective public health response to these trends relies on public health surveillance and laboratory systems, proven prevention and mitigation measures, scalable capacity to implement these measures, sensitive and specific diagnostics, and effective therapeutics. However, significant obstacles hinder successful implementation of these public health strategies. The recent emergence of , the first invasive tick to emerge in the United States in approximately 80 years, serves as the most recent example of the need for a coordinated public health response. Addressing the dual needs for innovation and discovery and for building state and local capacities may overcome current challenges in vector-borne disease prevention and control, but will require coordination across a national network of collaborators operating under a national strategy. Such an effort should reduce the impact of emerging vectors and could reverse the increasing trend of vector-borne disease incidence and associated morbidity and mortality.
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http://dx.doi.org/10.4269/ajtmh.18-0841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367643PMC
February 2019

A decade of vector control activities: Progress and limitations of Chagas disease prevention in a region of Guatemala with persistent Triatoma dimidiata infestation.

PLoS Negl Trop Dis 2018 11 6;12(11):e0006896. Epub 2018 Nov 6.

Center of Health Studies, Universidad del Valle de Guatemala, Ciudad de Guatemala, Guatemala.

Introduction: Chagas disease, a neglected tropical disease that affects millions of Latin Americans, has been effectively controlled in Guatemala after multiple rounds of indoor residual insecticide spraying (IRS). However, a few foci remain with persistent Triatoma dimidiata infestation. One such area is the municipality of Comapa, Department of Jutiapa, in the southeastern region of Guatemala, where control interventions appear less effective. We carried out three cross sectional entomological and serological surveys in Comapa to evaluate a decade of vector control activities. Baseline serological (1999) and entomological (2001-2) surveys were followed by three rounds of insecticide applications (2003-2005) and intermittent focal spraying of infested houses, until approximately 2012. Household inspections to determine entomological indices and construction materials were conducted in 2001, 2007 and 2011. Seroprevalence surveys were conducted in school-age children in 1999, 2007 and 2015, and in women of child bearing age (15-44 years) only in 2015. After multiple rounds of indoor residual sprayings (IRS), the infestation index decreased significantly from 39% (2001-2) to 27% (2011). Household construction materials alone predicted <10% of infested houses. Chagas seroprevalence in Comapa declined in school-aged children by 10-fold, from 10% (1999) to 1% (2015). However, seroprevalence in women of child bearing age remains >10%.

Conclusion: After a decade of vector control activities in Comapa, there is evidence of significantly reduced transmission. However, the continued risk for vector-borne and congenital transmission pose a threat to the 2022 Chagas disease elimination goal. Systematic integrated vector control and improved Chagas disease screening and treatment programs for congenital and vector-borne disease are needed to reach the elimination goal in regions with persistent vector infestation.
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http://dx.doi.org/10.1371/journal.pntd.0006896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6239342PMC
November 2018

Vital Signs: Trends in Reported Vectorborne Disease Cases - United States and Territories, 2004-2016.

MMWR Morb Mortal Wkly Rep 2018 May 4;67(17):496-501. Epub 2018 May 4.

Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, CDC, Fort Collins, Colorado.

Introduction: Vectorborne diseases are major causes of death and illness worldwide. In the United States, the most common vectorborne pathogens are transmitted by ticks or mosquitoes, including those causing Lyme disease; Rocky Mountain spotted fever; and West Nile, dengue, and Zika virus diseases. This report examines trends in occurrence of nationally reportable vectorborne diseases during 2004-2016.

Methods: Data reported to the National Notifiable Diseases Surveillance System for 16 notifiable vectorborne diseases during 2004-2016 were analyzed; findings were tabulated by disease, vector type, location, and year.

Results: A total 642,602 cases were reported. The number of annual reports of tickborne bacterial and protozoan diseases more than doubled during this period, from >22,000 in 2004 to >48,000 in 2016. Lyme disease accounted for 82% of all tickborne disease reports during 2004-2016. The occurrence of mosquitoborne diseases was marked by virus epidemics. Transmission in Puerto Rico, the U.S. Virgin Islands, and American Samoa accounted for most reports of dengue, chikungunya, and Zika virus diseases; West Nile virus was endemic, and periodically epidemic, in the continental United States.

Conclusions And Implications For Public Health Practice: Vectorborne diseases are a large and growing public health problem in the United States, characterized by geographic specificity and frequent pathogen emergence and introduction. Differences in distribution and transmission dynamics of tickborne and mosquitoborne diseases are often rooted in biologic differences of the vectors. To effectively reduce transmission and respond to outbreaks will require major national improvement of surveillance, diagnostics, reporting, and vector control, as well as new tools, including vaccines.
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http://dx.doi.org/10.15585/mmwr.mm6717e1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933869PMC
May 2018

Tick-Borne Zoonoses in the United States: Persistent and Emerging Threats to Human Health.

ILAR J 2017 12;58(3):319-335

Rebecca J. Eisen, PhD, is a Research Biologist in the Bacterial Diseases Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention in Fort Collins, Colorado. Kiersten J. Kugeler, PhD, is an Epidemiologist in the Bacterial Diseases Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention in Fort Collins, Colorado. Lars Eisen, PhD, is a Research Entomologist in the Bacterial Diseases Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention in Fort Collins, Colorado. Charles B. Beard, PhD, is a Branch Chief in the Bacterial Diseases Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention in Fort Collins, Colorado. Christopher D. Paddock, MD, is a Medical Officer/Pathologist in the Rickettsial Zoonoses Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention in Atlanta, Georgia.

In the United States, ticks transmit the greatest diversity of arthropod-borne pathogens and are responsible for the most cases of all vector-borne diseases. In recent decades, the number of reported cases of notifiable tick-borne diseases has steadily increased, geographic distributions of many ticks and tick-borne diseases have expanded, and new tick-borne disease agents have been recognized. In this review, we (1) describe the known disease agents associated with the most commonly human-biting ixodid ticks, (2) review the natural histories of these ticks and their associated pathogens, (3) highlight spatial and temporal changes in vector tick distributions and tick-borne disease occurrence in recent decades, and (4) identify knowledge gaps and barriers to more effective prevention of tick-borne diseases. We describe 12 major tick-borne diseases caused by 15 distinct disease agents that are transmitted by the 8 most commonly human-biting ixodid ticks in the United States. Notably, 40% of these pathogens were described within the last two decades. Our assessment highlights the importance of animal studies to elucidate how tick-borne pathogens are maintained in nature, as well as advances in molecular detection of pathogens which has led to the discovery of several new tick-borne disease agents.
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http://dx.doi.org/10.1093/ilar/ilx005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610605PMC
December 2017

Host-Seeking Phenology of Ixodes pacificus (Acari: Ixodidae) Nymphs in Northwestern California in Relation to Calendar Week, Woodland Type, and Weather Conditions.

J Med Entomol 2017 01 5;54(1):125-131. Epub 2016 Oct 5.

Vectorborne Diseases, Centers for Disease Control

Local knowledge of when humans are at elevated risk for exposure to tick vectors of human disease agents is required both for the effective use of personal protection measures to avoid tick bites and for implementation of control measures to suppress host-seeking ticks. Here, we used previously published data on the seasonal density of host-seeking Ixodes pacificus Cooley and Kohls nymphs, the primary vectors of Lyme disease spirochetes in the far western USA, collected across a broad habitat and climate gradient in northwestern California to identify predictors of periods of time within the year when questing nymphal density is elevated. Models based on calendar week alone performed similarly to models based on calendar week and woodland type, or meteorological variables. The most suitable model for a given application will depend on user objectives, timescale of interest, and the geographic extent of predictions. Our models sought not only to identify when seasonal host-seeking activity commences, but also when it diminishes to low levels. Overall, we report a roughly 5-7 month period in Mendocino County during which host-seeking nymphal densities exceed a low threshold value.
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http://dx.doi.org/10.1093/jme/tjw155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5229258PMC
January 2017

Update: Interim Guidance for Health Care Providers Caring for Pregnant Women with Possible Zika Virus Exposure - United States, July 2016.

MMWR Morb Mortal Wkly Rep 2016 Jul 25;65(29):739-44. Epub 2016 Jul 25.

CDC has updated its interim guidance for U.S. health care providers caring for pregnant women with possible Zika virus exposure, to include the emerging data indicating that Zika virus RNA can be detected for prolonged periods in some pregnant women. To increase the proportion of pregnant women with Zika virus infection who receive a definitive diagnosis, CDC recommends expanding real-time reverse transcription-polymerase chain reaction (rRT-PCR) testing. Possible exposures to Zika virus include travel to or residence in an area with active Zika virus transmission, or sex* with a partner who has traveled to or resides in an area with active Zika virus transmission without using condoms or other barrier methods to prevent infection.(†) Testing recommendations for pregnant women with possible Zika virus exposure who report clinical illness consistent with Zika virus disease(§) (symptomatic pregnant women) are the same, regardless of their level of exposure (i.e., women with ongoing risk for possible exposure, including residence in or frequent travel to an area with active Zika virus transmission, as well as women living in areas without Zika virus transmission who travel to an area with active Zika virus transmission, or have unprotected sex with a partner who traveled to or resides in an area with active Zika virus transmission). Symptomatic pregnant women who are evaluated <2 weeks after symptom onset should receive serum and urine Zika virus rRT-PCR testing. Symptomatic pregnant women who are evaluated 2-12 weeks after symptom onset should first receive a Zika virus immunoglobulin (IgM) antibody test; if the IgM antibody test result is positive or equivocal, serum and urine rRT-PCR testing should be performed. Testing recommendations for pregnant women with possible Zika virus exposure who do not report clinical illness consistent with Zika virus disease (asymptomatic pregnant women) differ based on the circumstances of possible exposure. For asymptomatic pregnant women who live in areas without active Zika virus transmission and who are evaluated <2 weeks after last possible exposure, rRT-PCR testing should be performed. If the rRT-PCR result is negative, a Zika virus IgM antibody test should be performed 2-12 weeks after the exposure. Asymptomatic pregnant women who do not live in an area with active Zika virus transmission, who are first evaluated 2-12 weeks after their last possible exposure should first receive a Zika virus IgM antibody test; if the IgM antibody test result is positive or equivocal, serum and urine rRT-PCR should be performed. Asymptomatic pregnant women with ongoing risk for exposure to Zika virus should receive Zika virus IgM antibody testing as part of routine obstetric care during the first and second trimesters; immediate rRT-PCR testing should be performed when IgM antibody test results are positive or equivocal. This guidance also provides updated recommendations for the clinical management of pregnant women with confirmed or possible Zika virus infection. These recommendations will be updated when additional data become available.
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http://dx.doi.org/10.15585/mmwr.mm6529e1DOI Listing
July 2016

County-Scale Distribution of Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae) in the Continental United States.

J Med Entomol 2016 Mar;53(2):349-86

The blacklegged tick, Ixodes scapularis Say, is the primary vector to humans in the eastern United States of the Lyme disease spirochete Borrelia burgdorferi, as well as causative agents of anaplasmosis and babesiosis. Its close relative in the far western United States, the western blacklegged tick Ixodes pacificus Cooley and Kohls, is the primary vector to humans in that region of the Lyme disease and anaplasmosis agents. Since 1991, when standardized surveillance and reporting began, Lyme disease case counts have increased steadily in number and in geographical distribution in the eastern United States. Similar trends have been observed for anaplasmosis and babesiosis. To better understand the changing landscape of risk of human exposure to disease agents transmitted by I. scapularis and I. pacificus, and to document changes in their recorded distribution over the past two decades, we updated the distribution of these species from a map published in 1998. The presence of I. scapularis has now been documented from 1,420 (45.7%) of the 3,110 continental United States counties, as compared with 111 (3.6%) counties for I. pacificus. Combined, these vectors of B. burgdorferi and other disease agents now have been identified in a total of 1,531 (49.2%) counties spread across 43 states. This marks a 44.7% increase in the number of counties that have recorded the presence of these ticks since the previous map was presented in 1998, when 1,058 counties in 41 states reported the ticks to be present. Notably, the number of counties in which I. scapularis is considered established (six or more individuals or one or more life stages identified in a single year) has more than doubled since the previous national distribution map was published nearly two decades ago. The majority of county status changes occurred in the North-Central and Northeastern states, whereas the distribution in the South remained fairly stable. Two previously distinct foci for I. scapularis in the Northeast and North-Central states appear to be merging in the Ohio River Valley to form a single contiguous focus. Here we document a shifting landscape of risk for human exposure to medically important ticks and point to areas of re-emergence where enhanced vector surveillance and control may be warranted.
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http://dx.doi.org/10.1093/jme/tjv237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844559PMC
March 2016

Whole genome multilocus sequence typing as an epidemiologic tool for Yersinia pestis.

Diagn Microbiol Infect Dis 2016 Apr 12;84(4):275-80. Epub 2015 Dec 12.

Division of Vector-Borne Diseases, Bacterial Diseases Branch, Centers for Disease Control and Prevention, Fort Collins, CO 80523. Electronic address:

Human plague is a severe and often fatal zoonotic disease caused by Yersinia pestis. For public health investigations of human cases, nonintensive whole genome molecular typing tools, capable of defining epidemiologic relationships, are advantageous. Whole genome multilocus sequence typing (wgMLST) is a recently developed methodology that simplifies genomic analyses by transforming millions of base pairs of sequence into character data for each gene. We sequenced 13 US Y. pestis isolates with known epidemiologic relationships. Sequences were assembled de novo, and multilocus sequence typing alleles were assigned by comparison against 3979 open reading frames from the reference strain CO92. Allele-based cluster analysis accurately grouped the 13 isolates, as well as 9 publicly available Y. pestis isolates, by their epidemiologic relationships. Our findings indicate wgMLST is a simplified, sensitive, and scalable tool for epidemiologic analysis of Y. pestis strains.
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http://dx.doi.org/10.1016/j.diagmicrobio.2015.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829196PMC
April 2016

Linkages of Weather and Climate With Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae), Enzootic Transmission of Borrelia burgdorferi, and Lyme Disease in North America.

J Med Entomol 2016 Mar;53(2):250-61

Lyme disease has increased both in incidence and geographic extent in the United States and Canada over the past two decades. One of the underlying causes is changes during the same time period in the distribution and abundance of the primary vectors: Ixodes scapularis Say and Ixodes pacificus Cooley and Kohls in eastern and western North America, respectively. Aside from short periods of time when they are feeding on hosts, these ticks exist in the environment where temperature and relative humidity directly affect their development, survival, and host-seeking behavior. Other important factors that strongly influence tick abundance as well as the proportion of ticks infected with the Lyme disease spirochete, Borrelia burgdorferi, include the abundance of hosts for the ticks and the capacity of tick hosts to serve as B. burgdorferi reservoirs. Here, we explore the linkages between climate variation and: 1) duration of the seasonal period and the timing of peak activity; 2) geographic tick distributions and local abundance; 3) enzootic B. burgdorferi transmission cycles; and 4) Lyme disease cases. We conclude that meteorological variables are most influential in determining host-seeking phenology and development, but, while remaining important cofactors, additional variables become critical when exploring geographic distribution and local abundance of ticks, enzootic transmission of B. burgdorferi, and Lyme disease case occurrence. Finally, we review climate change-driven projections for future impact on vector ticks and Lyme disease and discuss knowledge gaps and research needs.
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http://dx.doi.org/10.1093/jme/tjv199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844560PMC
March 2016

Climate change influences on the annual onset of Lyme disease in the United States.

Ticks Tick Borne Dis 2015 Jul 15;6(5):615-22. Epub 2015 May 15.

Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, 3150 Rampart Rd., Fort Collins, CO 80522, USA. Electronic address:

Lyme disease is the most commonly reported vector-borne illness in the United States. Lyme disease occurrence is highly seasonal and the annual springtime onset of cases is modulated by meteorological conditions in preceding months. A meteorological-based empirical model for Lyme disease onset week in the United States is driven with downscaled simulations from five global climate models and four greenhouse gas emissions scenarios to project the impacts of 21st century climate change on the annual onset week of Lyme disease. Projections are made individually and collectively for the 12 eastern States where >90% of cases occur. The national average annual onset week of Lyme disease is projected to become 0.4-0.5 weeks earlier for 2025-2040 (p<0.05), and 0.7-1.9 weeks earlier for 2065-2080 (p<0.01), with the largest shifts for scenarios with the highest greenhouse gas emissions. The more southerly mid-Atlantic States exhibit larger shifts (1.0-3.5 weeks) compared to the Northeastern and upper Midwestern States (0.2-2.3 weeks) by 2065-2080. Winter and spring temperature increases primarily cause the earlier onset. Greater spring precipitation and changes in humidity partially counteract the temperature effects. The model does not account for the possibility that abrupt shifts in the life cycle of Ixodes scapularis, the primary vector of the Lyme disease spirochete Borrelia burgdorferi in the eastern United States, may alter the disease transmission cycle in unforeseen ways. The results suggest 21st century climate change will make environmental conditions suitable for earlier annual onset of Lyme disease cases in the United States with possible implications for the timing of public health interventions.
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http://dx.doi.org/10.1016/j.ttbdis.2015.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631020PMC
July 2015

Collection and characterization of samples for establishment of a serum repository for lyme disease diagnostic test development and evaluation.

J Clin Microbiol 2014 Oct 13;52(10):3755-62. Epub 2014 Aug 13.

Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, USA

Serological assays and a two-tiered test algorithm are recommended for laboratory confirmation of Lyme disease. In the United States, the sensitivity of two-tiered testing using commercially available serology-based assays is dependent on the stage of infection and ranges from 30% in the early localized disease stage to near 100% in late-stage disease. Other variables, including subjectivity in reading Western blots, compliance with two-tiered recommendations, use of different first- and second-tier test combinations, and use of different test samples, all contribute to variation in two-tiered test performance. The availability and use of sample sets from well-characterized Lyme disease patients and controls are needed to better assess the performance of existing tests and for development of improved assays. To address this need, the Centers for Disease Control and Prevention and the National Institutes of Health prospectively collected sera from patients at all stages of Lyme disease, as well as healthy donors and patients with look-alike diseases. Patients and healthy controls were recruited using strict inclusion and exclusion criteria. Samples from all included patients were retrospectively characterized by two-tiered testing. The results from two-tiered testing corroborated the need for novel and improved diagnostics, particularly for laboratory diagnosis of earlier stages of infection. Furthermore, the two-tiered results provide a baseline with samples from well-characterized patients that can be used in comparing the sensitivity and specificity of novel diagnostics. Panels of sera and accompanying clinical and laboratory testing results are now available to Lyme disease serological test users and researchers developing novel tests.
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http://dx.doi.org/10.1128/JCM.01409-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4187768PMC
October 2014

Phylogeographic pattern and extensive mitochondrial DNA divergence disclose a species complex within the Chagas disease vector Triatoma dimidiata.

PLoS One 2013 5;8(8):e70974. Epub 2013 Aug 5.

Laboratório de Epidemiologia e Sistemática Molecular, Instituto Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brazil.

Background: Triatoma dimidiata is among the main vectors of Chagas disease in Latin America. However, and despite important advances, there is no consensus about the taxonomic status of phenotypically divergent T. dimidiata populations, which in most recent papers are regarded as subspecies.

Methodology And Findings: A total of 126 cyt b sequences (621 bp long) were produced for specimens from across the species range. Forty-seven selected specimens representing the main cyt b clades observed (after a preliminary phylogenetic analysis) were also sequenced for an ND4 fragment (554 bp long) and concatenated with their respective cyt b sequences to produce a combined data set totalling 1175 bp/individual. Bayesian and Maximum-Likelihood phylogenetic analyses of both data sets (cyt b, and cyt b+ND4) disclosed four strongly divergent (all pairwise Kimura 2-parameter distances >0.08), monophyletic groups: Group I occurs from Southern Mexico through Central America into Colombia, with Ecuadorian specimens resembling Nicaraguan material; Group II includes samples from Western-Southwestern Mexico; Group III comprises specimens from the Yucatán peninsula; and Group IV consists of sylvatic samples from Belize. The closely-related, yet formally recognized species T. hegneri from the island of Cozumel falls within the divergence range of the T. dimidiata populations studied.

Conclusions: We propose that Groups I-IV, as well as T. hegneri, should be regarded as separate species. In the Petén of Guatemala, representatives of Groups I, II, and III occur in sympatry; the absence of haplotypes with intermediate genetic distances, as shown by multimodal mismatch distribution plots, clearly indicates that reproductive barriers actively promote within-group cohesion. Some sylvatic specimens from Belize belong to a different species - likely the basal lineage of the T. dimidiata complex, originated ~8.25 Mya. The evidence presented here strongly supports the proposition that T. dimidiata is a complex of five cryptic species (Groups I-IV plus T. hegneri) that play different roles as vectors of Chagas disease in the region.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0070974PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733668PMC
March 2014

Dihydropteroate synthase mutations in Pneumocystis pneumonia: impact of applying different definitions of prophylaxis, mortality endpoints and mutant in a single cohort.

Med Mycol 2013 Aug 8;51(6):568-75. Epub 2013 Mar 8.

San Francisco General Hospital, Division of Pulmonary & Critical Care Medicine, University of California, San Francisco, California 94110, USA.

Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations are well-reported. Although sulfa prophylaxis generally is associated with DHPS mutant infection, whether mutant infection is associated with poorer clinical outcomes is less clear. The differing definitions of sulfa prophylaxis and the different mortality endpoints used in these studies may be one explanation for the conflicting study results. Applying different definitions of prophylaxis, mortality endpoints and DHPS mutant to 301 HIV-infected patients with Pneumocystis pneumonia, we demonstrate that prophylaxis, irrespective of definition, increased the risk of infection with pure mutant (any prophylaxis: AOR 4.00, 95% CI: 1.83-8.76, P < 0.001) but not mixed genotypes (any prophylaxis: AOR 0.78, 95% CI: 0.26-2.36, P = 0.65). However, infection with mutant DHPS, irrespective of definition, was not associated with increased mortality (all-cause or PCP death) at the three time-intervals examined (all P > 0.05). Future studies should standardize key variables associated with DHPS mutant infection as well as examine DHPS mutant subtypes (pure mutant vs. mixed infections) - perhaps even individual DHPS mutant genotypes - so that data can be pooled to better address this issue.
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http://dx.doi.org/10.3109/13693786.2013.770604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008324PMC
August 2013

The Lyme disease vaccine--a public health perspective.

Clin Infect Dis 2011 Feb;52 Suppl 3:s247-52

Department of Health and Human Services, Washington, DC, USA.

Lyme disease, which is caused by the spirochetal agent Borrelia burgdoferi, is the most common vector-borne illness in the United States. In 1998, the US Food and Drug Administration approved a recombinant Lyme disease vaccine that was later voluntarily withdrawn from the market by the manufacturer. Current Lyme disease prevention efforts focus on a combination of methods and approaches, including area acaricides, landscape management, host-targeted interventions, management of deer populations, and personal protective measures, such as the use of insect repellant and tick checks. Although these methods are generally safe and relatively inexpensive, the primary limitations of these methods are that their effectiveness has been difficult to demonstrate conclusively and that rates of compliance are generally poor. An effective human Lyme disease vaccine that has been adequately evaluated in the highest-risk population groups could be very beneficial in preventing Lyme disease; however, it would need to meet high standards regarding safety, efficacy, cost, and public acceptance.
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http://dx.doi.org/10.1093/cid/ciq115DOI Listing
February 2011

Assessing human risk of exposure to plague bacteria in northwestern Uganda based on remotely sensed predictors.

Am J Trop Med Hyg 2010 May;82(5):904-11

Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, 3150 Rampart Road, Fort Collins, CO 80522, USA.

Plague, a life-threatening flea-borne zoonosis caused by Yersinia pestis, has most commonly been reported from eastern Africa and Madagascar in recent decades. In these regions and elsewhere, prevention and control efforts are typically targeted at fine spatial scales, yet risk maps for the disease are often presented at coarse spatial resolutions that are of limited value in allocating scarce prevention and control resources. In our study, we sought to identify sub-village level remotely sensed correlates of elevated risk of human exposure to plague bacteria and to project the model across the plague-endemic West Nile region of Uganda and into neighboring regions of the Democratic Republic of Congo. Our model yielded an overall accuracy of 81%, with sensitivities and specificities of 89% and 71%, respectively. Risk was higher above 1,300 meters than below, and the remotely sensed covariates that were included in the model implied that localities that are wetter, with less vegetative growth and more bare soil during the dry month of January (when agricultural plots are typically fallow) pose an increased risk of plague case occurrence. Our results suggest that environmental and landscape features play a large part in classifying an area as ecologically conducive to plague activity. However, it is clear that future studies aimed at identifying behavioral and fine-scale ecological risk factors in the West Nile region are required to fully assess the risk of human exposure to Y. pestis.
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http://dx.doi.org/10.4269/ajtmh.2010.09-0737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861378PMC
May 2010

Genetic transformation of a Corynebacterial symbiont from the Chagas disease vector Triatoma infestans.

Exp Parasitol 2008 May 24;119(1):94-8. Epub 2008 Jan 24.

Department of Internal Medicine, University of New Mexico, 915 Camino Del Salud NE, CRF 305, Albuquerque, NM 87131, USA.

Insect-borne diseases have experienced a troubling resurgence in recent years. Emergence of resistance to pesticides greatly hampers control efforts. Paratransgenesis, or the genetic transformation of bacterial symbionts of disease vectors, is an alternative to traditional approaches. Previously, we developed paratransgenic lines of Rhodnius prolixus, a vector of Chagas disease in Central America. Here, we report identification of a Corynebacterial species as a symbiont of Triatoma infestans, a leading vector of Chagas disease in South America. We have modified this bacterium to produce an immunologically active single chain antibody fragment, termed rDB3. This study establishes the basis for generating paratransgenic T. infestans as a strategy for control of Chagas disease.
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http://dx.doi.org/10.1016/j.exppara.2007.12.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2635415PMC
May 2008

Performance of a molecular viability assay for the diagnosis of Pneumocystis pneumonia in HIV-infected patients.

Diagn Microbiol Infect Dis 2007 Feb 17;57(2):169-76. Epub 2006 Oct 17.

Division of Geographic Medicine, BBRB Box 7, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Pneumocystis pneumonia (PCP), caused by infection with Pneumocystis jirovecii, remains an important opportunistic infection in humans. A reverse transcriptase polymerase chain reaction assay has been shown to specifically detect viable P. jirovecii organisms. In the current study, we evaluated this assay on different types of respiratory samples. The assay had a diagnostic sensitivity of 100% and a specificity of 86% when applied to bronchoalveolar lavage samples. The assay's performance declined when applied to less invasive induced sputum and oropharyngeal wash (OPW) samples. The sensitivity, when applied to OPWs, was improved by examining multiple sequential OPW samples and was affected by clinical sampling parameters that could increase or decrease the number of potential organisms in the oropharynx. When used in conjunction with an optimized clinical sampling protocol, this assay may become a useful tool for detecting and monitoring P. jirovecii in minimally invasive clinical samples.
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http://dx.doi.org/10.1016/j.diagmicrobio.2006.08.015DOI Listing
February 2007

Genetic differences in Pneumocystis isolates recovered from immunocompetent infants and from adults with AIDS: Epidemiological Implications.

J Infect Dis 2005 Nov 13;192(10):1815-8. Epub 2005 Oct 13.

Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention (CDC), Fort Collins, CO 80521, USA.

Polymerase chain reaction analysis, direct DNA sequencing, and histological staining were used to determine whether Pneumocystis jirovecii was present in lung tissue specimens obtained, at autopsy, from 58 infants without identifiable immunodeficiency. The results of genotyping of these specimens were compared with the results of genotyping of specimens obtained from 384 human immunodeficiency virus (HIV)-infected adults with Pneumocystis pneumonia. P. jirovecii DNA was detected at the mitochondrial large subunit rRNA and dihydropteroate synthase loci in 100% and 53%, respectively, of the specimens obtained from infants. All specimens obtained from adults tested positive for P. jirovecii at both loci. Genotype distributions at both loci were significantly different in the 2 populations (P < .0001). The observation of different strains circulating in immunocompetent infants and HIV-infected adults suggests independent transmission cycles that warrant further study.
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http://dx.doi.org/10.1086/497381DOI Listing
November 2005

Severity and outcome of HIV-associated Pneumocystis pneumonia containing Pneumocystis jirovecii dihydropteroate synthase gene mutations.

AIDS 2005 May;19(8):801-5

Positive Health Program and Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California, San Francisco, California, USA.

Background: The impact of Pneumocystis jirovecii (formerly P. carinii) dihydropteroate synthase (DHPS) gene mutations on morbidity and mortality of Pneumocystis pneumonia (PCP) in HIV-positive patients is unclear.

Objective: To determine whether severity and outcome of HIV-associated PCP differs according to DHPS genotype.

Setting: A prospective, observational study in a university-affiliated county hospital.

Patients: The study included 197 patients with 215 microscopically confirmed PCP episodes and successfully sequenced DHPS genotypes; 175 (81%) episodes displayed mutant genotypes.

Main Outcome Measure: All-cause mortality within 60 days.

Results: The majority of patients (86%) with PCP containing Pneumocystis DHPS mutations survived. Although severity of PCP was comparable, there was a trend for more patients with mutant genotypes than patients with wild-type to require mechanical ventilation (14.3% versus 2.5%; P = 0.056) and to die (14.3% versus 7.5%, P = 0.31). Independent predictors of mortality at baseline were low serum albumin levels [odds ratio (OR), 4.62; 95% confidence interval (CI), 1.63-13.1; P = 0.004] and requiring intensive care within 72 h of hospitalization (OR, 5.06; 95% CI, 1.43-18.0; P = 0.012).

Conclusion: The majority of HIV-infected patients with PCP containing mutant Pneumocystis DHPS genotypes survived. Mortality was related primarily to the underlying severity of illness. However, a trend towards increased mortality in episodes of PCP containing mutant DHPS genotypes was observed and this warrants further study.
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http://dx.doi.org/10.1097/01.aids.0000168974.67090.70DOI Listing
May 2005

Current epidemiology of Pneumocystis pneumonia.

Emerg Infect Dis 2004 Oct;10(10):1713-20

University of Southern California, Los Angeles, California, USA.

Pneumocystis pneumonia (PCP) has historically been one of the leading causes of disease among persons with AIDS. The introduction of highly active antiretroviral therapy in industrialized nations has brought about dramatic declines in the incidence of AIDS-associated complications, including PCP. In the adult population, the incidence of PCP has significantly decreased, but it remains among the most common AIDS-defining infections. Similar declines have been documented in the pediatric population. In much of the developing world, PCP remains a significant health problem, although its incidence among adults in sub-Saharan Africa has been debated. This review discusses the epidemiology of PCP during the current era of the AIDS epidemic. Although fewer cases of PCP occur in industrialized countries, increasing drug-resistant HIV infections, possible drug-resistant PCP, and the tremendous number of AIDS cases in developing countries make this disease of continued public health importance.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3323247PMC
http://dx.doi.org/10.3201/eid1010.030985DOI Listing
October 2004

Nested clade and phylogeographic analyses of the Chagas disease vector Triatoma brasiliensis in Northeast Brazil.

Mol Phylogenet Evol 2004 Jul;32(1):46-56

Departamento de Medicina Tropical, Instituto Oswaldo Cruz-Fiocruz, Av. Brasil 4365, Rio de Janeiro, RJ 21045-900, Brazil.

Triatoma brasiliensis (Hemiptera: Reduviidae: Triatominae) is the most important Chagas disease vector in the semiarid areas of Northeast Brazil. We analyzed mitochondrial cytochrome b sequence variation among 136 individuals representing 16 populations from across the species' distribution. Neighbor-joining and parsimony tree-building methods were used in conjunction with nested clade analysis to describe the systematics and phylogeography of this species. Our results indicate that T. brasiliensis is composed of four genetically distinct chromatic forms (referred to as brasiliensis, macromelasoma, juazeiro, and melanica) that present inter-population divergence values (0.027-0.119, corrected K2-p) and a pattern of haplotype geographic distribution compatible with the existence of a species complex. As a consequence, such forms can be treated as isolated targets in vector control programs. We were unable to infer what is shaping the population structure of the brasiliensis form as we obtained mutually exclusive causes of structure, namely a barrier to gene flow caused by past population fragmentation, and isolation by distance between populations (which would permit gene flow). We found indication of mitochondrial DNA introgression occurring among forms in putative hybrid zones.
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http://dx.doi.org/10.1016/j.ympev.2003.12.011DOI Listing
July 2004

A prospective, blinded study of quantitative touch-down polymerase chain reaction using oral-wash samples for diagnosis of Pneumocystis pneumonia in HIV-infected patients.

J Infect Dis 2004 May 16;189(9):1679-83. Epub 2004 Apr 16.

Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA.

Oral-wash samples obtained during 113 episodes of suspected Pneumocystis pneumonia (PCP) in human immunodeficiency virus-infected patients were tested by use of a quantitative touch-down PCR (QTD PCR) assay. QTD PCR had a sensitivity of 88% and a specificity of 85%. Treatment for PCP prior to oral wash collection had an impact on the sensitivity, and PCR-positive oral-wash samples obtained within < or =1 day of treatment from patients without PCP had significantly fewer copies per tube than did those from patients with PCP; thus, application of a post hoc cut-off value of 50 copies/tube increased the specificity to 100%. QTD PCR of oral-wash samples can be an accurate and noninvasive method for diagnosis of PCP.
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http://dx.doi.org/10.1086/383322DOI Listing
May 2004