January 21-23, Tom Harkin Global Communication Center Centers for Disease Control and Prevention 1600 Clifton Road Atlanta, Georgia

Transcription

1 Proceedings of a Regional Workshop to Assess Research and Outreach Needs in Integrated Pest Management to Reduce the Incidence of Tick-borne Diseases in the Southern United States January 21-23, 2009 Tom Harkin Global Communication Center Centers for Disease Control and Prevention 1600 Clifton Road Atlanta, Georgia

2 Introduction Reports of tick-borne diseases are increasing globally. Many factors may be contributing to this increase. These include better recognition of the diseases, increased awareness by the public and health care, the coattail effect of Lyme disease popularity, and many others. The southern United States have long been endemic for a number of tickborne diseases, the most severe being Rocky Mountain spotted fever. As molecular techniques have become more widely adopted, the recognition of other etiologic agents has occurred. Rickettsial species once thought to be of little to no pathogenicity have been shown to be causing human infections. Tick species discounted as vectors of pathogens to humans because of limited human biting have become much more important in certain geographic areas. We must reassess the current information on the prevalence and distribution of these pathogens in the southern United States and determine better means of prevention and control for the ticks and their associated pathogens. This workshop was convened in Atlanta, Georgia to provide a venue for discussion of topical issues by a diverse group of individuals working at all levels to combat these diseases. Participants from local, state, and federal agencies joined university researchers to assess the problems and needs for the southern region. Much of the current work has been funded and is focused on Borrelia burgdorferi, but a broader approach is needed for the growing pathogen list. The participants were broken into workgroups representing topic areas of their interest. The groups met for two days and presented their findings at the end of the meeting. Each group took a different approach to the discussions and presentation of their findings. It is hoped that this proceedings may serve as a blueprint for planning of future activities and that funding agencies may use the proceedings as a report of the current problems and needs for public health. Charles S. Apperson and William L. Nicholson, Editors of the Proceedings -2-

3 Organizing Committee Charles S. Apperson Department of Entomology North Carolina State University Raleigh, NC Herb Bolton Army Environmental Programs USDA, CREES Washington, DC Kristen Borré Southern Coastal Agromedicine Center East Carolina State University Greenville, NC Marcia Herman-Giddens Tick-Borne Infections Council of North Carolina, Inc. Pittsboro, NC Nolan Newton Public Health Pest Management Section NC Department of Environment, Health, and Natural Resources Raleigh, NC William L. Nicholson Rickettsial Zoonoses Branch Centers for Disease Control and Prevention Atlanta, GA Carol Pilcher North Central Region IPM Center Evaluation and Measurement Working Group Iowa State University Ames, IA Susan Ratcliffe North Central Region IPM Center University of Illinois Urbana, IL -3-

4 Acknowledgements The workshop was hosted by the Centers for Disease Control and Prevention in their new Tom Harkin Global Communications Center. The workshop was sponsored by the USDA Southern Region Integrated Pest Management Center, Bayer Environmental Science, Focus Diagnostics, and Novozymes Biologicals, Inc. We are grateful to Anirudh Dhammi for allowing us to use his picture of Amblyomma americanum on the title page of the proceedings. Mention of any commercial name is for identification only and does not represent endorsement of a company or a product. The opinions expressed are those of the authors and are not representative of the views of their respective agencies. -4-

5 Contents Overall Summary.. 6 Disease Surveillance, Laboratory Diagnosis, and Case Reporting Tick Biology and Ecology Pathogen Biology and Ecology Tick Bite Prevention and Tick Control Institutional Policies and Inter-Agency Interactions List of Participants Group Photograph

6 Overall Summary Tick-borne diseases (TBDs) are an uncommon but nevertheless significant source of morbidity and mortality in the southern United States. Notably, the incidence of TBDs is increasing in the south as a partial result of increased surveillance and improved case reporting by the medical community, but also because of the detection and description of new diseases and their etiological agents. Ticks are inexorably linked to their wildlife hosts. The process of suburbanization of woodlands and recreational activities will undoubtedly continue to expose people to ticks and the zoonotic agents that they carry. Accordingly, the public health burden imposed by TBDs will likely continue to increase. Reduction of pathogen transmission and TBDs is challenging and will require a concerted and collaborative effort of professionals from a wide range of disciplines. Disease prevention programs are built on a foundation of knowledge derived from field-based eco-epidemiology studies. In particular, such studies should include: Physician-based cohort studies of patients presumptively diagnosed with a TBD in geographic areas reporting a high incidence, including the procurement of clinical specimens for pathogen identification by culture and molecular methods. The majority of TBDs are presumptively diagnosed based on limited serological testing. Coarse and fine scale longitudinal environmental surveys and ecological studies of the interaction of ticks, wildlife, companion animals and people, particularly at the sites where patients were infected. Long term surveillance programs for detection of emerging tick vectors and pathogens should be coordinated with the medical community, public and veterinary health professionals, wildlife biologists and others. Field-based evaluations of educational or behavioral interventions in areas where TBDs occur to define public knowledge and attitudes that are preventing the adoption of protective practices against TBDs. A major dilemma in public health is that despite the availability of effective tools for preventing tick bites, protective behaviors are often not adopted. Shortage of resources is a major issue preventing public agencies from addressing TBDs effectively and proactively. Lack of funding, particularly at the federal level for laboratory and field-based studies of TBDs, is a major impediment to development of new diagnostic techniques and intervention strategies for prevention of TBDs. Agency and institutional support for these research efforts will remain crucial in the battle against these problems in the southern United States. -6-

7 Disease Surveillance, Laboratory Diagnosis, and Case Reporting Discussion leaders: Wayne Hogrefe and William L. Nicholson Focus group members: Marina Eremeeva, Chris Evans, Laurel Garrison, Marcia Giddens-Hermans, John Krebs, Jennifer McQuiston, Valerie Mock, Marc Traeger, and Carl Williams Introduction The proper diagnosis of tick-borne diseases relies on many facets including clinical presentation, exposure to competent vectors, the geographical location of the potential exposure, and laboratory tools to accurately detect the exposure to the pathogen. Access to the laboratory tools to diagnose tick-borne diseases has a variety of barriers, but a primary barrier is relatively low disease incidence, which in turn dictates a low financial investment by both the private and public sectors. Also emerging diseases have a substantial time lag between disease discovery, gaining understanding of pathobiology, and the development of proper laboratory tools for the study and diagnosis of the disease. Understanding the biology of the pathogen, the vector (if even known), and the pathobiology in the diseased host are typically required for the subsequent development of the laboratory tools to aid in the diagnosis. Laboratory diagnostics are the primary tools utilized in disease surveillance algorithms with the clinical history to establish disease causality. The entirety of laboratory data, clinical data, and epidemiologic information are then used to establish case reporting. Therefore, the validation and interpretation criteria of laboratory diagnostic results are critical for the correct laboratory-based diagnosis and the downstream disease surveillance and case reporting activities. Over the past 20 years the number of rickettsial or ehrlichial pathogens causing human disease in the United States has increased from just several to more than 15 (Nicholson et al. 2009). In the Southeastern US the following tickborne pathogens can be routinely found: Borrelia burgdorferi, Ehrlichia chaffeensis, Rickettsia rickettsii, Anaplasma phagocytophilum, E. ewingii, R. parkeri, and many others at significantly lower detection rates. Marshall et al. (2002) have also found elevated E. chaffeensis seroprevalance in the South- Central US with seroprevalance rates varying from 2% in Kentucky to as high as 22% in North Carolina. Similar results were also reported for R. rickettsii seroprevalance in children with positive rates ranging from 3.5% to 22% in the southeastern US (Marshall et al. 2003). Recently an increase in the number of reported cases of Rocky Mountain spotted fever (RMSF) has been found in specific geographic regions of the US including Oklahoma, Missouri, Tennessee, Arkansas, and North Carolina. Some of this increase could be due to the changing ecology of the natural cycles, as has been noted in the southwestern -7-

8 US (Demma et al. 2005), or exposure to other emerging rickettsial agents. As the number of tick-borne pathogens causing human disease has increased, the limitations of the current laboratory diagnostic tools have become more apparent (Raoult and Parola 2008). Apperson et. al. (2008) have suggested the recent increase in RMSF cases may be due to Candidatus R. amblyommmii rather than R. rickettsii alone as antibodies to both pathogens are cross-reactive and detected using R. rickettsii serologic reagents. The diagnosis of tick-borne diseases is based on predominantly serologic results as the direct detection of many tick-borne pathogens is limited due to low level of circulating antigen or nucleic acid present only during the acute phase of these infections. The dilemma of current laboratory serologic assays for diagnosis of tick-borne diseases is the lack of standardized reagents, as well as the lack of validated and characterized representative disease-state serum panel/collection/bank to establish diagnostic criteria such as clinically significant antibody titer levels. The CDC has published diagnostic criteria for several diseases such as RMSF, ehrlichioses, and anaplasmosis as a guide to diagnosis and management of those illnesses (Chapman et al. 2006). However, reagents to standardize those serologic assays are not generally available. In 1999, a series of workshops were held that helped establish working criteria for the laboratory diagnosis of E. chaffeensis infection (Walker et al. 2000). An extension of these workshops was the establishment of a serum bank containing sera with known clinical history and antibody titers made available through the CDC for laboratories to use to calibrate their serology results to other laboratories. However, serum panels and standardized criteria for the other tick-borne pathogens beside B. burgdorferi (distributed through CDC Bacterial Diseases Branch, Ft. Collins) and E. chaffeensis are not available. Individual laboratories have attempted to establish serologic criteria to limit serologic testing to the appropriate patient populations; however, such practices have not included procedures to either standardize reagents or interpretative criteria [a reference is needed]. The typical algorithm used to link laboratory diagnosis and disease surveillance/case reporting for rickettsial diseases is shown in figure 2. The outcome of case reporting is not only tied to laboratory diagnosis but also to the chain of authority from the health care professional to the city/county/state health departments to the CDC. Disease surveillance is typically passive and may not be monitored on a national scale. Thus, the resulting case reporting may not always reflect true disease incidence. Active surveillance is typically linked to an investigation of outbreaks and may more accurately reflect true disease incidence. Active surveillance is typically only performed in a limited geographic location and is costly to maintain for any significant period. Therefore, active surveillance may lead to a spike in reported cases, but the spike may only last the length of the active surveillance period. Also impacting surveillance data is the use of electronic reporting tools versus the traditional hard copy system such as the CDC s Case Report Form. A comparison of National Electronic Telecommunications System for Surveillance (NETSS) and the Tick-Borne Rickettsial Disease Case Report Form (CRF) for historical trends in RMSF shows -8-

9 a similar trend and an increased RMSF incidence rate when NETSS data is compared to CRF data. A current example of where passive surveillance can lead to active surveillance, or at least define a need to pursue active surveillance, is the recent increase in reported cases of RMSF in multiple states. Of particular interest is the increase of reported cases of RMSF associated with a much lower morbidity/mortality than has historically been associated with RMSF. The implementation of an active surveillance to investigate the recent changes in RMSF incidence will require cooperative effort between primary care healthcare workers and public health officials at the local, state and national level. The implementation and duration of such a surveillance program will be dictated in part by the cost of implementing the program. A variety of factors besides surveillance activities will impact case reporting, these factors include enhanced case-finding efforts, climatic changes, variations in vector/pathogen populations, increased healthcare provider interest, and increased testing efforts (Openshaw et al. in prep.). For the tick-borne pathogens concerned in this report several issues have emerged that require an assessment of how suspected cases are reported and whether the case definition may need modification. For example, more patients with clinically compatible symptoms are found to be seropositive for a particular pathogen when the clinical presentation does not fit the historical symptoms/presentation. How should these individuals be reported? Others question whether chronic rickettsiosis really exists? If a patient is afebrile and seropositive, should this person be diagnosed with rickettsiosis? And finally how do we determine true incidence via case reporting when no accurate data is available as to the number of individuals actually tested? Laboratory Diagnostics Primary Concerns/Barriers to Success. The laboratory tools for the diagnosis of tick-borne diseases are essentially limited to molecular detection methods in acute disease and serologic methods for confirmation later in the course of disease (see Fig. 1). The molecular tools provide the best opportunities to diagnose acute tick-borne infection; however, the majority of cases rely on serologic results for diagnosis. Although reagents for the accurate detection of B. burgdorferi infection (Lyme disease) have advanced over the last 10 years as has the availability of defined Lyme disease serum panels from the CDC, no such tools currently exist for the other tick-borne diseases. The serologic tools for non-lyme tick-borne disease are almost exclusively limited to antibody-based immunofluorescence reagents. Although ELISA tools have been developed through the use of native and recombinant proteins, these specific reagents have not been thoroughly characterized with well-established serum panels. The barriers to improve the serologic tools available for clinical diagnostics include the lack of confirmed patient disease-state sera to test the robustness of the -9-

10 reagents, lack of funding to identify, secure and accumulate such materials, and a relatively small market of such diagnostic reagents to attract commercial investment in such reagents. The changing regulatory environment in regards to the use of analyte-specific reagents (ASR) may potentially limit access to new reagents that may prove useful to diagnose these disease. Table 1 lists the current barriers to identifying and implementing new diagnostic tools for tickborne diseases. The proper application of the existing and future technology must include physician education on the appropriate specimens, appropriate timing of specimens within the illness, and the appropriate interpretation of the results in the context of clinical illness (Garrison and Nicholson 2007). When an education effort was implemented at a large clinical hospital, dramatic increases in proper testing strategy and results interpretability was seen (Crump et al. 2004). While having a limited utility for acute diagnosis, serologic tests can provide very meaningful data when timed correctly relative to the course of infection. Although molecular techniques are more widely available, their application will be limited until we see an increase in collection of adequate clinical specimens for each particular pathogen. Remedial Activities. A variety of remedial actions can be undertaken to enhance the laboratory diagnostic tools for tick-borne disease and they are briefly outlined below. All of the proposed activities have the common issue of identifying funding sources in order to carry out the activity. Procurement of clinically defined specimens Establish partnerships between local, state, and national public health laboratories and commercial laboratories to facilitate the process of active surveillance. The partnerships will enhance the probability of acquisition of clinically defined specimens. This may include incentive programs on a local or regional level to engage primary care physicians to participate in the active surveillance program to acquire clinical specimens. Make the clinically defined specimens available for assay development improvements at both public health and commercial entities. Provide clinically defined samples for proficiency testing between testing laboratories. Establish standardized criteria for serologic assays including procedural parameters, analytical thresholds, and immunoglobulin class-specificity. Expand availability and exchange of defined clinical specimens outside of an active surveillance effort by collaboratively collecting complete sets of clinical samples (paired sera, acute blood, acute skin biopsy if appropriate). The collaboration would be between local healthcare providers, public health facilities, and commercial laboratories and would be on a smaller scale than an active surveillance effort. The collaboration -10-

11 would facilitate exchange of specimens on a small scale for reciprocal proficiency testing and assay validations. Expand research and development activities Encourage further research into new serologic and molecular assays for rickettsial diseases to improve sensitivity and specificity for early clinical diagnosis. Encourage the evaluation of recombinant antigens singularly, or in combination, as alternatives to whole cell antigens for serology. Encourage further research into the use of Western immunoblot assays to better define the immunologic response to rickettsial (sensu lato) pathogens and their differentiation. Encourage further research into new serologic assays and testing strategies for Lyme disease, particularly any assays for differentiating B. burgdorferi infections from other Borrelia infections or STARI. Expand molecular testing capability Expand the implementation of molecular testing procedures at the state public health and commercial laboratories to increase testing capacity for both clinical diagnosis and disease surveillance. Establish standardized criteria for molecular assays, including procedural parameters, analytical thresholds, and specificity of amplification. Encourage collection and testing of appropriately timed clinical specimens that provide the most meaningful information to the physician. Expand public and private laboratory collaboration Establish standardization of analyte specific reagents used for lab developed tests, produced for limited distribution to public health laboratories, or commercial use. Strengthen the commitments to make standardized analyte specific reagents, calibrated controls, and assay kits available to public health laboratories by establishing mechanisms for acquisition or production of bulk materials by both commercial and public health entities. Collaborate with commercial laboratories to standardize interpretive language present in patient laboratory reports. Facilitate the transfer of this interpretative information to original healthcare provider so proper interpretation of test results and proper follow-up and surveillance requirements are understood. Education -11-

12 Develop innovative methods to educate healthcare providers on testing strategies, test availability, and test interpretation to enhance proper patient care. Further educate physicians, labortorians, epidemiologists, and other public health workers to ensure that appropriate specimens are collected at the appropriate time in the illness, and tested with the proper assay to provide the most successful and efficient results. Improve submission of suitable specimens taken at the optimal time during the illness so that certain problematic issues might be better resolved. (e.g., the spotted fever concern for acute diagnosis). -12-

13 Disease Surveillance and Case Reporting Primary Concerns. The pathway to enhanced surveillance and case reporting first involves improvement of the laboratory tools and interpretation criteria of laboratory results (in particular, serologic results). The resources required to develop and implement improved diagnostic tools and diagnostic criteria, as outlined above, can be provided through active surveillance programs. Active surveillance programs can be structured so that well-defined clinical materials can be obtained through the primary healthcare professionals involved in the active surveillance. Such clinical materials can be utilized for reagent development, assay development, validation of current and future assays, and proficiency testing. The primary barrier to conducting active surveillance is funding. A second concern is the need for timely modifications to case definitions so that accurate case reporting can be obtained. As described in the Introduction, the current apparent increase in RMSF incidence may be due to a new, related pathogen, to an attenuated species, or due to the lack of strict or revised case criteria. In the latter case, as different patient populations are tested such as afebrile individuals, a more restricted case definition may be required to ensure true cases of RMSF are recorded. Remedial Activities. Surveillance and case reporting efforts will be enhanced through any improvements in the laboratory diagnostic tools outlined above. Remedial activities outlined below will also enhance surveillance and case reporting independent of enhancements made to the laboratory diagnostic tools. Some of the activities below were also identified as needs/requirements for enhanced laboratory tools; however, they are listed again since they would improve surveillance and case reporting even if they were not implemented for advancing laboratory components. Collaboration Collaborate with the Council for State and Territorial Epidemiologists (CSTE), CDC, and State Public Health Laboratories to propose changes in the current Rocky Mountain spotted fever (RMSF) case definition to reflect the fact that diseases caused by spotted fever group rickettsial species are aggregated into this longstanding named category. Collaborate with the CSTE, CDC, and State Public Health Laboratories to propose further modifications to the case definitions for Ehrlichiosis, Anaplasmosis, Q Fever, and RMSF to establish standard laboratory parameters and strict surveillance (epidemiological) thresholds for assays available for laboratory confirmation of suspect cases of tick-borne illness. Encourage better transfer of clinical and epidemiological information on each specimen submitted for diagnostic testing so that useful interpretation of any laboratory results may be made. -13-

14 Establish a more efficient infrastructure to facilitate the reporting of tickborne disease cases electronically. Incorporate pertinent clinical, epidemiological, and laboratory information into any centralized system to improve disease surveillance. Develop incentives to increase participation of primary care physicians in providing a reasoned diagnostic workup that would ultimately be reflected in better case reporting. Education Educate physicians, laboratorians, epidemiologists, and other public health workers on the concept that a threshold ( cut-off value ) for an assay has different meanings and uses for laboratory (analytical), clinical (medical), or surveillance (epidemiological) purposes. Educate physicians, laboratorians, epidemiologists, and other public health workers on the quality and limitations of existing data distributed through surveillance systems, informative publications, and other means. Administrative Consider the concept of sentinel sites in endemic areas so that tick-borne diseases may be monitored in a more intensive manner. Evaluate whether a sentinel site approach would improve disease surveillance of tick-borne diseases which have an inherently focal pattern of occurrence. Incorporate new technology and assays into disease surveillance systems as they become established, validated, and transferred into public health and commercial laboratories. Seek administrative and budgetary support for targeted active surveillance projects to better define epidemiology of tick-borne diseases, specimen collection timing and types, and optimize testing methods and procedures. References Cited Apperson, C.S., Engber, B., Nicholson, W. L., Mead, D.G., Engel, J., Yabsley, M. J., Dail, K., Johnson, J., and Watson, D.W Rickettsial diseases in North Carolina: Is Rickettsia amblyommii a possible cause of rickettsiosis reported as Rocky Mountain spotted fever? Vector Borne Zoonot. Dis. 8: Chapman, A.S., Bakken, J.S., Bloch, K.C., Buckingham, S.C., Dasch, G.A., Eremeeva, M.E., Dumler, J.S., Folk, S.M., Krusell, A., Marshall, G.S., McQuiston, J.H., Nicholson, W.L., Ohl, C.A., Paddock, C.D., Sexton, D.J., Storch, G.A., Swerdlow, D.L., and Walker, D.H Diagnosis and management of tick-borne rickettsial diseases: Rocky Mountain spotted fever, ehrlichioses, and anaplasmosis--united States (A practical guide for -14-

15 physicians and other health-care and public health professionals). MMWR, Recommendations and Reviews 55 (RR-4): [March 31, 2006] Crump, J.A., Corder, J.R., Henshaw, N.G., and Reller, L.B Development, implementation, and impact of acceptability criteria for serologic tests for infectious diseases. J. Clin. Microbiol. 42: Demma, L., Traeger, M., Nicholson, W.L., Paddock, C.D., Blau, D., Eremeeva, M., Dasch, G., Levin, M., Singleton, J., Zaki, S., Cheek, J., Swerdlow, D., and McQuiston, J Rocky Mountain spotted fever from an unexpected tick vector in Arizona. New Engl. J. Med. 353: Garrison, L.E., and Nicholson, W.L Diagnostic testing for Rocky Mountain spotted fever: unraveling the uncertainty. Georgia Epidemiol. Report 23 (4): 1 3. Marshall, G.S., Jacobs, R.F., Schutze, G.E., Paxton, H., Buckingham, S.C., DeVincenzo, J.P., Jackson, M.A., San Joaquin, V.H., Standaert, S.M., Woods, C.R., and the Tick-borne Infections in Children Study Group Ehrlichia chaffeensis seroprevalence among children in the Southeast and South-Central regions of the United States. Arch. Pediatr. Adolesc. Med. 156: Marshall, G.S., Jacobs, R.F., Schutze, G.E., Paxton, H., Buckingham, S.C., DeVincenzo, J.P., Jackson, M.A., San Joaquin, V.H., Standaert, S.M., Woods, C.R., and the Tick-borne Infections in Children Study Group Antibodies reactive to Rickettsia rickettsii among children living in the Southeast and South-Central regions of the United States. Arch. Pediatr. Adolesc. Med. 157: Nicholson, W.L., Sonenshine, D.E., Lane, R.S., and Uilenberg, G Ticks (Ixodidae). Pp In: Mullen, G.R. and Durden, L.A. (eds.). Medical and Veterinary Entomology, 2nd edition. Academic Press (Elsevier), New York, N.Y. Openshaw, J.J., Swerdlow, D.L., Krebs, J.W., Holman, R.C., Mandel, E., Harvey, A., Haberling, D., Massung, R.F., and McQuiston, J.H Rocky Mountain spotted fever in the United States, : interpreting contemporary increases in incidence. (in preparation). Raoult, D., and Parola, P Rocky Mountain spotted fever in the USA: a benign disease or a common diagnostic error? Lancet Infect. Dis. 8: Walker, D.H., and the Task Force on Consensus Approach for Ehrlichiosis ASM News 66 (5):

16 Time Course of Tick-borne Infectious Disease Tick bite Transfer to host Onset of symptoms Clinical recovery Grace Period Subclinical infection Symptomatic Convalescence 4-48 hr days 0-30 days LAB: Bacteremia (PCR) days LAB: Serologic detection PO* EPI: Surveillance detection *Prevention opportunity Figure 1. Diagnosis of tick-borne diseases. -16-

17 Figure 2. Linking laboratory diagnoses with disease surveillance. -17-

18 Table 1. Barriers for new laboratory tools for diagnostics. Reagents Lack of clinically defined sample panels to evaluate new diagnostic tools Small market to support commercial development of new technology Performance of commercial and public health laboratory reagents have not been compared nor standardized Lack of well-defined comparator assays, relatively small patient population, and the size of sample populations required for clinical trials for regulatory submission relative to a small market product are barriers to the availability of FDA-approved diagnostic products Lab-Developed Tests Lack of proficiency serum panels for use at testing laboratories (commercial or public) to establish laboratory and staff performance Lack of uniformity in interpretation between testing labs to define values of diagnostic titer for serologic assays Lack of standardization between labs for crucial test components (i.e., the antibody isotype specificity of antibody conjugates) Cost to perform proper validation of lab-developed tests that is required to meet the current standards for lab-developed tests -18-

19 Tick Biology and Ecology Discussion leaders: Rebecca Eisen, Lars Eisen, and Joe Piesman Focus group members: Charles Apperson, Lance Durden, David Gaines, Graham Hickling and Uriel Kitron Introduction Tick-borne diseases (TBDs) present an increasing public health challenge in the southern United States; in particular, a provisional total of 2,276 cases of Rocky Mountain Spotted Fever (RMSF) and 848 cases of Human Monocytic Ehrlichiosis (HME) were reported to CDC in 2008 (CDC 2008a,b). These potentially fatal TBDs are most commonly reported from the southern U.S. and the numbers of reported cases have increased sharply over the past 5 years. This raises the question of whether we understand enough about tick ecology to move forward with developing and implementing novel, improved management approaches. The focus group acknowledges the wide range of biological and ecological studies on ticks undertaken in the South (Sonenshine and Stout 1968; Barnard 1986; Bloemer et al. 1990; Mount et al. 1993; Durden and Oliver 1996). However, most of these studies were directed toward interactions of vector ticks with livestock or wildlife. We conclude that there are key knowledge gaps that presently block progress towards more effective management of TBDs of public health importance in the southern U.S. These knowledge gaps are summarized below, together with recommendations for high priority research areas. A: Big Picture Questions and Recommendations Spatial and temporal distribution and abundance of human-biting vector ticks Accurately depicting the spatial distribution of human-biting ticks is fundamental to identifying areas where humans are at risk for exposure to tickborne pathogens. The likelihood of enzootic maintenance of tick-borne pathogens and the probability of human encounters with ticks increases with tick abundance. Knowledge of when and where ticks are most abundant can aid in: 1) targeting of limited prevention and control resources to areas presenting the greatest risk; 2) empowering the public to make informed decisions regarding the need for personal protective measures; and 3) informing physicians of spatial and temporal risk patterns to ensure that TBDs are recognized and treated (Eisen and Eisen 2008). Distribution (presence or absence) information is available at the county level for commonly human-biting tick species in most southern states (i.e., the lone star tick Amblyomma americanum, the American dog tick Dermacentor variabilis, and the black-legged tick Ixodes scapularis). Although other minor tick species -19-

20 may be important for enzootic maintenance of a given tick-borne pathogen, the distributions of these ticks are poorly defined because they are not easily collected by drag sampling or through examination of small mammals or lizards. Field sampling is not routinely or systematically conducted and most information on current distributions is based on studies conducted decades ago. Because tick distribution and abundance patterns have changed in recent decades as a consequence of changing host abundance (particularly the explosive growth of deer populations) and land use patterns, existing distribution maps may be inaccurate. Due to ecological heterogeneity within counties which often translates to variation in tick abundance, risk assessment studies should aim for accurate abundance estimates at sub-county scales. Furthermore, tick abundance changes seasonally. To most effectively target prevention and control measures, we must identify periods of peak abundance. In short, there is a need to move beyond static, presence/absence distribution maps at a county level to temporally-dynamic finer-scale (sub-county) models of tick abundance by life stage. Ideally, these models should include information on pathogen prevalence. The following actions are required to develop temporally-dynamic and spatially-explicit tick vector abundance models: Systematic collection and enumeration of ticks (by species and life stage) across habitat gradients Identification of GIS or remotely-sensed ecological correlates of tick abundance that can be used to extrapolate abundance estimates across broad geographic areas. Field studies aimed at quantifying seasonal patterns in host-seeking behavior in relation to ecological predictors such as habitat type, temperature, and rainfall Laboratory evaluation of transmission efficiency of tick-borne pathogens for each tick species. This information will aid in identifying critical vector abundance thresholds required for enzootic maintenance of tick-borne pathogens and these estimates can serve as targets for tick reduction Pathogen/tick/host cycles Relative to the northeastern United States, we have an incomplete understanding of pathogen/tick/host cycles in the South. Systematic collections of tick species along a north-south cline has begun with the recent CDC-funded Yale survey (Diuk-Wasser et al. 2006). This work needs to be extended by moving to a finer spatial scale at selected sites, and by sampling over all seasons to gather the phenological data that are critical for modeling pathogen transmission cycles. -20-

21 It is also important to appreciate that the South is heterogeneous with regard to climate, habitat types, and host communities. There is already strong evidence that pathogen/tick/host cycles in coastal habitats are markedly different from those found a short distance inland. Tick phenologies west of the Appalachians may differ from those of populations at similar latitudes to the east. The effects of macro-scale weather patterns on tick abundance, host abundance and especially disease prevalence need investigation. For example, are there time-lagged effects of gross changes in weather such as decreased rainfall or unusually low winter temperatures? Future field studies need to be designed to obtain robust baseline data that will enable tracking over coming decades of how long term changes in spatial and temporal risk patterns relate to climate change. Such studies also need to take into account that climate change may also alter host populations and human activities leading to exposure to tick habitats. It seems likely that tick distributions are changing, but the reasons for and mechanisms of such changes are not clear. An ability to predict future change in distribution and abundance patterns has public health benefits in that it enables physicians and veterinarians to be alerted to the need for increased vigilance for increasing TBD incidence among human patients and companion animals. To this end, a better understanding of the means by which ticks disperse is important. Which hosts are the most important dispersal vehicles for which species of ticks -- birds, mammals and other hosts? Are ticks present in some areas such as migratory bird flyways as a consequence of dispersal by birds into areas in which they would not otherwise establish viable populations? Population genetic studies of ticks could provide information on the origin and movement of ticks as well as the movement of pathogens. For example, genetic analyses of ticks along the leading edge of Lyme disease in southern states could help determine whether northern genotypes are moving south and whether genetic differences underpin putative questing and host selection behavior between the North and South (Qiu et al. 2002). Surveillance and communication For non-reportable TBDs, human case data cannot be mapped to define the geographic scale and extent of the problem. For reportable diseases, the validity of probable cases needs more rigorous investigation (particularly for Lyme disease and RMSF). Inadequate case data are presently a major stumbling block for ecological studies on widespread tick species, because such studies require human case data to help focus ecological survey efforts. More comprehensive information is needed on which tick species (and life stages) bite humans in the various southern states. Passive submissions of ticks from humans are almost certainly biased towards the less familiar species. There is also a need for a better understanding of which pathogens are being -21-

22 maintained in a region within cryptic cycles, and thus potentially detectable by certain kinds of surveillance but nevertheless of negligible risk to humans. Having this kind of information is critical for effective interpretation of field ecological/epidemiological study results to health providers and the public. Greater clarity is needed because detection of vector ticks, even when infected with pathogens, does not necessarily equate to human health risk. Recommendations Create a national map of vector tick species that is seasonally explicit; Systematically collect seasonal tick and pathogen data at a suitable spatial scale for modeling tick/habitat relationships at replicate enhanced surveillance sites in several southern states. Sites should encompass areas with high and low tick abundance areas to investigate why ticks are more abundant in some areas; Establish baseline tick population data at multiple sites using standardized methods, so that long term changes potentially related to climate change can later be assessed; Gather better information, from several states, on which ticks species and life stages attack people, and when. To support the efforts recommended above, develop an EIS-like training program in field disease ecology and vector biology. B: Pathogen-specific Questions and Recommendations Lyme disease and Ixodes scapularis ecology The overarching question is: why is the incidence of Lyme disease low in Southern states. Several factors may contribute to this. First, nymphs appear to quest for hosts in a manner that rarely leads to human exposure. In the South, adults are frequently removed from humans whereas nymphal bites are rare (Merten and Durden 2000). Nymphs of I. scapularis are considered the primary vectors of Borrelia burgdorferi in the Northeast and the infrequent exposure of humans to nymphs in the South likely is a major reason for low LD incidence. Second, tick hosts that are poor spirochete reservoirs, or even zooprophylactic (lizards), may contribute more to tick feeding than in the Northeast and thus decrease the intensity of enzootic spirochete transmission (Apperson et al. 1993). It is not proven however that this explanation is applicable throughout the South for example in Tennessee where lizard abundance is low. Is the apparent lack of mammal-oriented questing behavior in southern I. scapularis a response to the host community, or a consequence of their population genetics? Moreover, are northern biotypes of I. scapularis moving southwards, and does this have implications for future Lyme disease risk? -22-

23 Recommendations: Conduct fine-scale micro-habitat studies of I. scapularis in several sites in the South, assessing abundance of each life stage using standardized methods to allow for meta-analysis. Determine the seasonal cycles of each life stage at these sites where and when are ticks questing? Micro-habitat analysis: what is different about the habitats where I. scapularis nymphs are collected? Are there vegetation structure, host or microclimate differences? Develop better methods for collecting I. scapularis immatures in the South. Clarify what hosts southern I. scapularis are feeding on, to test the lizard hypothesis. New blood meal analysis methods may provide a way forward. Population genetic studies on I. scapularis nymphs from northern and southern populations, and on nymphs removed from different hosts (e.g. mice vs lizards). Rocky Mountain Spotted Fever A. americanum and D. variabilis ecology It is not clear whether recent marked increases in RMSF reports in several southern states represent a genuine increase in this disease, or increased reporting of less intense infections associated with other Spotted Fever Group Rickettsiae (SFGR). Better epidemiological follow-up is needed to validate these case data. Several tick species (A. americanum, D. variabilis and in certain situations also the brown dog tick Rhipicephalis sanguineus) may serve as vectors of SFGR. Dermacentor variabilis seems to be in decline in many areas, and there is some evidence that R. amblyommii is highly prevalent and responsible for atypical RMFS cases (Apperson et al. 2008). So the research focus should include both D. variabilis and A. americanum. Amblyomma maculatum and Rickettsia parkeri Rickettsia parkeri was first reported as a human infection in 2004 (Paddock 2005), although the organism had been identified over 60 years earlier. Human infection is characterized by clinical findings similar to, and possibly confused with, RMSF. However, an eschar at the bite site with a maculopapular rash provides evidence of possible R. parkeri infection. Numerous cases of the infection have been confirmed in the United States. These cases were associated with the Gulf Coast tick, Amblyomma maculatum, in which field studies have demonstrated infection by the rickettsiae (Sumner et al. 2007). Only limited information of the field biology of this tick is available (summarized in -23-

24 Goddard and Paddock 2005). Given the growing recognition of its importance as a vector, studies of the field ecology of A. maculatum are warranted. Recommendations: Determine which ticks occur at sites where spotted fever case patients were likely exposed (this will require interviews of case patients to determine the most likely site of exposure to the infected tick). Undertake enhanced epidemiological follow-up so that studies can be conducted both for bona fide cases of RMSF and for disease caused by other SFGR. Undertake longitudinal studies of tick populations in peridomestic sites, to establish which ticks pose the greatest risk. Undertake fine-scale and large-scale studies of A. americanum, A. maculatum and D. variabilis distribution in relation to habitat type and host abundance. Investigate whether decline in old field habitat correlates with decline in the abundance of D. variabilis? Where they occur in proximity to human RMSF cases, populations of R. sanguineus should be tested for infection with SFGR, especially R. rickettsii. Undertake host blood meal studies of A. americanum, A. maculatum and D. variabilis to better understand the role of hosts, other than deer. Ehrlichioses A. americanum ecology Since Ehrlichia chaffeensis was described as the etiologic agent causing Human Monocytic Ehrlichiosis in the southern United States (Anderson et al. 2001), this pathogen has become one of the greatest emerging vector-borne public health threats in the country, with a case-fatality rate of 2.7% (Walker et al. 2004). The expanding distribution and increasing abundance of the principal vector of E. chaffeensis, namely A. americanum (Anderson et al. 1993), is likely a key driver for the emerging health threat posed by HME. Given the predilection of A. americanum to feed on reservoir competent deer, why are infection rates of E. chaffeensis generally low in this tick? Are E. chaffeensis infections higher for mainland populations compared to on islands? What impact does R. amblyommii or other rickettsial infections in A. americanum have on transmission of E. chaffeensis? Fine scale habitat studies of the distribution of A. americanum nymphs and adults would provide data for spatial modeling so that acarological risk of tick bites could be estimated. -24-

25 Habitats associated with high and low abundance of A. americanum should be studied to determine environmental factors that are affecting ticks survival. Anecdotal reports suggest that both the distribution and abundance of A. americanum have increased dramatically in recent years. Can a data base be established to test whether the populations of A. americanum are truly expanding? Tularemia D. variabilis and A. americanum ecology Tularemia is caused by the bacterium Francisella tularensis, which can be transmitted to humans through a variety of routes including tick- or insect bite, handling of infected animals, contact with or ingestion of infected water, food, or soil, and inhalation of infectious aerosol. Arkansas and Missouri represent the epidemiological focus of tularemia in the U.S. In this region, the majority of human cases appear to be caused by Francisella tularensis tularensis (type A), and exposure is presumed to be primarily tick-borne (Staples et al. 2006). This assertion is supported by a recent GIS-based model of human risk of exposure to F. tularensis that identified environmental factors associated with tick habitat as significant predictors of risk (Eisen et al. 2008). However, it is largely unknown which tick species or life stages serve as the primary vector(s) of F. tularensis tularensis to humans. The co-occurrence of human tularemia cases and peak host-seeking activity of human-biting ticks implicate A. americanum nymphs or adults, or D. variabilis adults as the primary vectors to humans in this region (Eisen 2007). Future laboratory studies are required to systematically assess transmission efficiency of human-biting ticks infected with F. tularensis, by species and life stage, and thus compliment the results of older transmission studies (Eisen 2007).. These should be complimented by field studies aimed at determining fine-scale abundance patterns of human-biting vectors, and elucidation of enzootic cycles of F. tularensis. Conclusion Field ecological studies on a large scale are expensive and logistically challenging. Given the complex situation in the South whereby a single tick species may vector several zoonotic pathogens, and a single pathogen may be vectored by several tick species, it is important that public health agency structures not impede opportunities to gain the maximum value from such field studies when they do occur. Funding is urgently needed for studies on tick ecology and field epidemiology of TBDs in the South. In particular, there is a need to move beyond static, presence/absence distribution maps at a county level to temporally-dynamic fine-scale (sub-county) models of tick abundance by life stage. Ideally, these models should include information on host preferences and pathogen prevalence. -25-

26 References Cited Anderson, B.E., Dawson, J.E., Jones, D.C., and Wilson, K.H Ehrlichia chaffeensis, a new species associated with human ehrlichiosis. J. Clin. Microbiol. 29: Anderson, B.E., Sims, K.G., Olson, J.G., Childs, J.E., Piesman, J.F., Happ, C.M., Maupin, G.O., and Johnson, B.J Amblyomma americanum: a potential vector of human ehrlichiosis. Am. J. Trop. Med. Hyg. 49: Apperson, C.S., Levine, J.F., Evans, T.L., Braswell, A., and Heller, J Relative utilization of reptiles and rodents as hosts by immature Ixodes scapularis (Acari: Ixodidae) in the coastal plains of North Carolina. Exptl. Appl. Acarol. 17: Apperson, C.S., Engber, B., Nicholson, W.L., Mead, D.G., Engel, J., Yabsley, M.J., Dail, K., Johnson, J., and Watson, D.W Tick-borne diseases in North Carolina: is Rickettsia amblyommii a possible cause of rickettsiosis reported as Rocky Mountain spotted fever? Vector Borne Zoonot. Dis. 8: Barnard, D.R Density perturbation in population of Amblyomma americanum (Acari: Ixodidae) in beef cattle forage areas in response to two regimens of vegetation management. J. Econ. Entomol. 79: Bloemer, S.R., Mount, G.A., Morris, T.A., Zimmerman, R.H., Barnard, D.R., and Snoddy, E.L Management of lone star ticks (Acari: Ixodidae) in recreational areas with acaricide applications, vegetative management, and exclusion of white-tailed deer. J. Med. Entomol. 27: Centers for Disease Control and Prevention Provisional cases of infrequently reported notifiable diseases (<1,000 cases reported during the preceding year)-united States, week ending January 3, 2009 (53 rd week). MMWR 2008a. 57: Centers for Disease Control and Prevention Provisional cases of selected notifiable diseases, United States, weeks ending January 3, 2009 and December 29, 2007 (53 rd week). MMWR 2008b. 57: Diuk-Wasser, M.A., Gatewood, A.G., Cortinas, M.R., Yaremych-Hamer, S., Tsao, J., Kitron, U., Hicling, G., Brownstein, J.S., Walker, E., Piesman, J., and Fish, D Spatiotemporal patterns of host-seeking Ixodes scapularis nymphs (Acari: Ixodidae) in the United States. J. Med. Entomol. 43: Durden, L.A., and Oliver, Jr., J.H Ecology of Ixodes scapularis and Lyme disease in coastal Georgia, U.S.A. Pp In Needham, G.R., Mitchell, R., Horn, D.J., and Welbourn, W.C. (eds.). Proc. IX Intl Congress Acarol. Symposia, Vol. II. July 17-22, Ohio Biological Survey, Columbus, OH, USA. Eisen, L A call for renewed research on tick-borne Francisella tularensis in the Arkansas-Missouri primary national focus of tularemia in humans. J. Med. Entomol. 44:

27 Eisen, R.J., and Eisen, L Spatial modeling of human risk of exposure to vector-borne pathogens based on epidemiological versus arthropod data. J. Med. Entomol. 45: Eisen, R.J., Mead, P.S., Meyer, A.M., Pfaff, L.E., Bradley, K.K., and Eisen, L Ecoepidemiology of tularemia in a nine-state region of the south-central United States. Am. J. Trop. Med. Hyg. 78: Goddard, J., and Paddock, C.D Observations on distribution and seasonal abundance of the Gulf Coast tick in Mississippi. J. Med. Entomolo. 42: Merten, H.A., and Durden, L.A A state-by-state survey of ticks recorded from humans in the United States. J. Vector Ecol. 25: Mount, G.A., Haile, D.G., Barnard, D.R., and Daniels, E New version of LSTSIM for computer simulation of Amblyomma americanum (Acari: Ixodidae) population dynamics. J. Med. Entomol. 30: Paddock, C.D Rickettsia parkeri as a paradigm for multiple causes of tickborne spotted fever in the western hemisphere. Ann. N.Y. Acad. Sci. 1063: Qiu, W.G., Dykhuizen, D.E., Acosta, M.S., and Luft, B.J Geographic uniformity of the Lyme disease spirochete (Borrelia burgdorferi) and its shared history with tick vector (Ixodes scapularis) in Northeastern United States. Genetics 160: Sonenshine, D.E., and Stout, J.J Use of old-field habitats by the American dog tick, Dermacentor variabilis. Ann. Entomol. Soc. Am. 61: Sumner, J.W., Durden, L.A., Goddard, J., Stromdahl, E.Y., Clark, K.L., Reeves, W.K., and Paddock, C. D Gulf Coast ticks (Amblyomma maculatum) and Rickettsia parkeri, United States. Emerg. Infec. Dis. 13: Staples, J.E., Kubota K.A., Chalcraft, L.G, Mead, P.S., and Petersen, J.M Epidemiologic and molecular analysis of human tularemia, United States, Emerg. Infect. Dis. 12: Walker, D.H., Ismail, N., Olano, J.P., McBride, J.W., Yu, X.J., and Feng, H.M Ehrlichia chaffeensis: a prevalent, life-threatening, emerging pathogen. Trans. Am. Clin. Climatol. Assoc. 115:

28 Pathogen Biology and Ecology Discussion leaders: Kevin Macaluso, Christopher D. Paddock, and Michael Yabsley Focus group members: Ed Breitschwerdt, Kerry Clark, Greg Dasch, Barbara Johnson, Susan Little, Douglas Norris, Allen Richards, and Ellen Stromdahl Abstract Several tick-borne pathogens in the genera Anaplasma, Ehrlichia, Borrelia, and Rickettsia occur in the southern United States. Compared to the historical record and greater scrutiny of tick-borne pathogens in other regions of the United States, particularly the Northeast, many gaps exist in the recognized ecology of these microorganisms in the southern United States. Multiple species of these bacteria exist in tick populations that may influence the ecology of pathogen transmission. In addition, the epidemiology of historically recognized tick-borne bacterial diseases has perhaps been clouded because of cross-reactivity observed between mildly pathogenic or nonpathogenic species and highly pathogenic species when relatively non-specific diagnostic assays are used to diagnose these diseases. A more complete understanding of the pathogen ecology is needed, particularly as it appears that important vectors such as Amblyomma americanum, appear to be increasing in number and distribution throughout the southern United States. The expanding list of bacterial species associated with ticks, including many not implicated conclusively with any known disease of humans or animals, further complicates these assessments. Presented here is a statement on the topic and pathogens that require additional research. Introduction The discussion of pathogen ecology included three presentations that broadly covered the natural histories of some of the best recognized and most historically identified tick-borne agents, such as Rickettsia rickettsii and Borrelia burgdorferi, but concentrated primarily on the knowledge that exists for several important tickborne pathogens that have emerged in the southern United States during the last 30 years. Highlighted in these presentations were overviews of recognized pathogens represented by Ehrlichia, Anaplasma, Borrelia, and Rickettsia spp., as well as some that appear on the cusp of emerging pathogen status, but currently lack the required elements to be considered human pathogens. Following these overviews, a focus group of experts in tick-borne pathogen ecology in the southern United States convened to discuss some of the critical needs in the study of the ecology of tick-borne pathogens. This review discusses the salient points of each presentation, and provides a consensus opinion of several of the crucial knowledge gaps in our understanding of pathogen ecology, some of the perceived or real barriers to the acquisition of this knowledge, and -28-

29 recommendations for enhancing and facilitating the study of these tick-borne pathogens. Ehrlichia, Anaplasma, and Borrelia spp. During the last three and a half decades, several newly recognized, tick-borne, bacterial pathogens have been identified, including Borrelia burgdorferi, Ehrlichia chaffeensis, E. ewingii, the Panola Mountain Ehrlichia (PME) and Anaplasma phagocytophilum. These pathogens are maintained in zoonotic cycles involving different vectors and wildlife reservoirs. Borrelia burgdorferi and A. phagocytophilum are transmitted by Ixodes spp., primarily Ixodes scapularis, and utilize a variety of rodent hosts as reservoirs. E. chaffeensis, E. ewingii, and Ehrlichia sp. PME are transmitted by A. americanum and utilize, or are believed to use, white-tailed deer as a principal reservoir host (Paddock and Yabsley 2007). Other microorganisms of unknown pathogenicity have been identified in these ticks, including several Rickettsia spp., Coxiella spp., variants of A. phagocytophilum, and Borrelia lonestari. Considerable research has been conducted on the natural history of Ehrlichia chaffeensis. While white-tailed deer are the principal reservoirs, alternative wildlife hosts (e.g., raccoons and coyotes) can become infected and may be rare hosts. Field and experimental studies suggests that white-tailed deer may be important reservoirs for both E. ewingii and Ehrlichia sp. PME. In contrast, the natural history of A. phagocytophilum is poorly understood. Similar to B. burgdorferi, the variant of A. phagocytophilum that is associated with human illness (Ap-hu) is maintained in rodents and transmitted by I. scapularis; however, additional variants of A. phagocytophilum (Ap-var 1-4) have been identified in white-tailed deer and I. scapularis. Additional work is needed to understand the zoonotic potential of these variants and if distinct transmission cycles exist for the Ap-hu and Ap-var variants. A major gap in our knowledge of Lyme disease is the paucity of confirmed, autochthonous Lyme disease cases in the southern United States. Enzootic cycles of B. burgdorferi have been identified in southern rodents and ticks, and genetic studies have shown that southern isolates of B. burgdorferi s. s. are similar to northern isolates (Oliver et al. 2003; Oliver et al. 2008). The southeastern United States is rich in Borrelia species; in addition to B. burgdorferi, at least five other Borrelia spp. have been identified in wildlife and/or tick vectors (Rudenko et al. 2009). One of these, B. lonestari, is commonly detected in white-tailed deer and lone star ticks and is one putative agents of Southern Tick Associated Rash Illness (STARI) although evidence for infections in humans is lacking (Wormser et al. 2005). Four other B. burgdorferi sensu lato species (B. bissetti, B. andersoni, B. americana, and B. carolinensis) infect rodents, lagomorphs, or lizards in the southeastern United State and to date, none have been associated with human infections. -29-

30 Rickettsia amblyommii and other Spotted Fever group rickettsiae of unknown pathogenicity. Similar to the increased recognition of various Ehrlichia, Anaplasma, and Borrelia spp. the potential for vertebrate infection, there is amplified detection of rickettsial species that are peripherally linked to human disease, but lack some of the prerequisites to be considered a true human pathogen. Rickettsia species are obligate intracellular gram negative bacteria that parasitize vertebrates and invertebrates. Several tick-associated species appear to be tick endosymbionts and infections produce no obvious adverse effect on the arthropod host and quite possibly are never transmitted to vertebrates. Other species are highly pathogenic to the tick vector and the vertebrate host. Considering the expanding diversity of rickettsiae, it is likely that a wide spectrum of invertebrate and vertebrate responses exist between these two extremes. With respect to tick-borne spotted fever group Rickettsia (SFGR), there is a close relationship between the bacteria and the arthropod vector and the tick can actually serve as the reservoir for the infection. In addition to horizontal transmission of rickettsiae to vertebrate hosts, considered a requirement for pathogenic SFGR, ticks maintain these organisms by vertical transmission (both transstadial and transovarial) and thus every life cycle stage is potentially infected. There are at least 16 well-characterized or proposed rickettsial species in the United States and only 4 of these have been associated definitely with diseases of humans. The presence of nonpathogenic bacteria in tick populations, e.g. Rickettsia peacockii in Dermacentor andersoni and Ixodes rickettsial endosymbiont in I. scapularis, likely have a major influence on the frequency, or rather, infrequency of rickettsial pathogens in a tick population (Burgdorfer et al. 1981b). Of particular interest in the category of potentially emerging rickettsioses is the increased recognition of Rickettsia amblyommii as a suspected etiological agent of human disease (Apperson et al. 2008); yet, unequivocal evidence of human infection is still lacking (Nicholson et al. 2009). Initially described in the hemocytes of field-caught A. americanum in the mid 1970 s (Burgdorfer et al. 1974; Loving et al. 1978), laboratory studies indicated that R. amblyommii was non-infectious for meadow voles (Burgdorfer et al. 1974). Additional studies demonstrated human exposure to R. amblyommii-infected A. americanum in the absence of clinical signs further suggesting non-transmissibility to humans (Burgdorfer et al. 1975; Jiang et al. 2010). A more recent study demonstrated a rash in a patient fed upon by a R. amblyommii-infected A. americanum; however, patient samples were not assessed for R. amblyommii infection (Billeter et al. 2007). Steady detection of R. amblyommii was recorded throughout the 1980 s with molecular characterization and generation of an isolate deemed non-infectious for guinea pigs (Burgdorfer et al. 1981a). Similar to other rickettsial species described at the time Rickettsia montanensis (formerly R. montana), Rickettsia rhipicephali, and Rickettsia rickettsii a generalized infection of the vector was observed; however, in contrast to these other rickettsial species, the infection of -30-

31 ticks was considered to be milder (Burgdorfer et al. 1981b). The A. americanumassociated Rickettsia was referred to as R. amblyommii in the mid 1990 s (Stouthard and Fuerst 1995) and, although not formally designated, this name is generally accepted for this organism (or Rickettsia). Subsequent to its initial description, R. amblyommii is often detected in A. americanum throughout the southeastern United States and likely has a distribution that is the same as the tick host A. americanum. Rickettsia amblyommii has been identified outside the United States (Labruna et al. 2004, 2007; Parola et al. 2007). With the advent of more sensitive and specific molecular techniques to detect rickettsiae in invertebrate hosts, most reports now place the prevalence of R. amblyommii in wild-caught ticks at rates up to 90% (Mixson et al. 2006; Stromdahl et al. 2008; Smith et al. 2010). The apparent high prevalence of R. amblyommii in nature is likely relevant to the ecology of other rickettsial pathogens in the increasingly important tick vector A. americanum. The ecology and disease causing potential for vertebrates and transmissibility of R. amblyommii by ticks deserves further attention. Rickettsia rickettsii and Rickettsia parkeri. The natural histories of tick-borne pathogens and the epidemiology of the various diseases that these agents cause in human hosts are inextricably linked. In this context, a thorough understanding of the ecology of these pathogens is essential to accurately describe the distribution and determinants of tick-borne diseases. By example, the discovery of a second pathogenic SFGR, Rickettsia parkeri, occurring in sympatry with R. rickettsii (the etiological agent of Rocky Mountain spotted fever; RMSF) in the southeastern U.S., provides new perspectives of the conventionally accepted epidemiology of RMSF (Paddock et al. 2008). The rates of tick infection with R. rickettsii or R. parkeri are particularly salient ecologic features of these rickettsiae. Data from almost all contemporary surveys for R. rickettsii in nature report its occurrence in less than 1% of the ticks evaluated (Burgdorfer 1988; Gage et al. 1994; Philip and Casper 1981). Indeed, surveys for this pathogen, even in areas considered endemic for RMSF, often fail to identify a single infected tick (Ammerman et al. 2004; Dergousoff et al. 2009). In contrast, multiple surveys of Gulf Coast ticks (Amblyomma maculatum) collected from Florida, Georgia, and Mississippi reveal rates of infection with R. parkeri that range from 11%-40% (Sumner et al. 2007). The relative frequencies of these 2 rickettsiae in nature suggests that at least some, and possible many, of the reported cases of RMSF represent infections with R. parkeri, or possibly other pathogenic SFGR, that reside in human biting ticks in the United States (Paddock 2009). These type of data must also be balanced with the unprecedented increase in reported cases of RMSF and the marked declines in case-fatality rates for RMSF during the last decade (Chapman et al. 2001; MMWR 2009), and an expanding clinical spectrum of RMSF, that extends from subclinical seroconversion to rapidly fatal illness (Graf et al. 2008; Marshall et al. 2003). A better understanding of the true range of virulence of naturally occurring strains of R. -31-

32 rickettsii is needed to resolve these epidemiologic conundrums. Ecological investigations that include efforts to cultivate new isolates of pathogenic SFGR will provide the better tools to address questions of virulence that have confounded discussions of RMSF for more than 75 years. Recognized needs in the study of pathogen ecology. Contemporary ecologic surveys reveal clearly that many more tick-borne pathogens exist than were appreciated as recently as 35 years ago. Compounding these findings is the ambiguous nature of some rickettsial species and the rediscovery of some rickettsial pathogens. The pathogen ecology focus group recognized that these tick-borne bacterial pathogens are not likely to operate independently of each other and that there may be many undescribed ecological factors contributing to the current proliferation of tick-borne bacteria. Based on the initial presentations, there were discussions to address some of the overarching needs of researchers in the field of pathogen ecology, including facilitating pathogen availability, the mechanisms of generating and maintaining a reliable microbial repository, increasing awareness of tick-borne diseases and the economic importance of studying and understanding the complex microbial communities in ticks that include pathogens and nonpathogenic bacterial species, delineating the role of tick-borne pathogens in chronic diseases, standardizing methods for field research and tick and microbial characterization, enhancing interactions with federal regulators to determine more rational rules for the study of tick-borne bacteria, and developing an accessible toolbox of materials and reagents (e.g. clean ticks, low-passage isolates, etc.) to facilitate research on tick-borne diseases. Recommendations to facilitate research in pathogen ecology Elevate the status of tick-borne diseases. Worldwide, tick-borne pathogens are an important cause of morbidity and mortality; in some places rivaling mosquito-borne pathogens as the number one cause of illness. Because of their importance, there should be some recognition of tick-borne pathogens by abatement programs which currently are focused on mosquito control. These holistic vector control programs could provide services for a wide range of pathogens including those transmitted by fleas, ticks, mosquitoes, and biting flies. The group recognized that the best research results are obtained through collaboration and interdisciplinary programs. Future development of interdisciplinary projects that involve entomologists, microbiologists, infectious disease specialists, wildlife biologists, pathologists, is encouraged. In addition, it is important to recognize that scientists from other disciplines, such as virology, can help broaden the thought process and improve research goals. Education of new vector-borne disease specialists is needed. The group discussed the limited availability of training programs that provide integrated -32-

33 programs in medical entomology and pathogen ecology. Another avenue that was discussed to provide cross-disciplinary training included researchers presenting to non-traditional audiences such as at medical or pediatric, veterinary medicine, ecology, or ecosystem health conferences. The latter groups would be especially important given the increased need to recognize that tick-borne disease research should become more ecosystem focused with the understanding that ticks and potential reservoir hosts are present in dynamic systems that are rapidly changing. Address funding obstacles. The group also discussed the difficulty in determining the appropriate agency to submit large-scale tick-borne projects that are 1) ecologically-based; and, 2) involve both non-pathogen and multiple pathogens that include rickettsial, borrelial, and protozoan pathogens which span across multiple review panels as well as programmatic areas. The multipathogen proposals should be encouraged as co-infections are being increasingly recognized and these poly-infections can be more severe than single pathogen infections. Develop accessible resources for research. Low passage isolates of tickborne pathogens are needed for characterization studies (e.g., biochemical, transmission, antigen expression, etc.). Currently few tick-borne pathogens (or suspected pathogens) are readily cultivable and those that are, few isolates exist for use in research. Significant progress has been made since the development of several embryonic tick cell lines (reviewed in Munderloh and Kurtti 1995). However, access to these new isolates can be problematic due to difficulties in submitting cultures to national and international culture collections, many of which will not accession organisms that only grow within tick cells. Adaptation of these organisms to more routinely available cell lines should improve availability of isolates. Numerous studies have shown that organisms have the ability to change after long-term culture so attempts should be made to disseminate or archive low-passage isolates. Develop rational regulations for work with live agents. There needs to be more rational approaches to containment issues related to many of these organisms. More appropriate criteria should be established regarding work with for several of the species that have low or no evidence of pathogenicity. Currently, regulations are based on genus-wide restrictions that were developed for the most virulent pathogens of the group. Modification of these restrictions would allow more laboratories to engage in research on tick-borne disease agents. Current recommendations have created difficulties at many institutions in working with several of these agents, including Ehrlichia and Rickettsia species. As an example, it should be more clearly recognized that SFGR vary greatly in pathogenicity and that not all SFGR require BSL-3 practices. It was suggested that more prudent guidelines be determined through collaboration with experienced rickettsiologists and other experts to modify BMBL5-33-

34 recommendations for some species or strains that are not recognized as pathogens or have a well-documented history of low virulence in vertebrates. Develop standard methods for field research. Numerous studies on the ecology of tick-borne pathogens have been conducted and they have provided data that have significantly improved our knowledge of these organisms. However, it can be difficult to compare data between some studies because study designs may differ substantially such as the scale of the study (local vs. county vs. region), diagnostic methods (serology vs. PCR vs. culture), or geographic region. It was recommended that multiple lines of evidence be collected when conducting field studies on tick-borne pathogens. This should include culture (as a gold standard) for those pathogens for which culture conditions are known. For uncultivable agents, DNA-based studies can be utilized but assays used should be validated for sensitivity and specificity because some wildlife or vector species may be infected with previously uncharacterized organisms that may cross-react with well-characterized assays. Because of this, multiple gene targets should be utilized combined with sequence analysis of amplicons to confirm identity. As a supplement to DNA-based assays, a return to various conventional techniques, including inoculation of susceptible laboratory animal species with tick tissues should be considered when attempting to assess pathogenicity. For serologicbased studies, consideration should be given to the antigen used as some antigens may cross-react with related organisms more than other antigens. Research data are more meaningful if independently verified; therefore, researcher collaborations with other laboratories to verify findings, at least on a subset of samples, are encouraged. Many tick-borne pathogens in the United States have a wide distribution that is shared with their respective tick vectors. Considerable research may be conducted on a pathogen and vector in one region but further studies in other regions would be needed to fully understand regional differences in the natural history. Differences in climate, habitat, and densities and community structures of potential reservoir or dilution hosts and vectors can have a significant impact on the natural history of an organism. These regional differences can also influence the initial, peak, and duration of vector activity as well as presence or absence of endosymbionts which may alter the ecology of tick-borne organisms. Therefore, research on these organisms across their entire geographic range was encouraged. While recognized that a certain level of quality is required for validity of field studies, the adoption of a standard surveillance protocol was not advised because of difficulties related to limitations of equipment availability in all labs or presence of novel organisms that would ultimately limit creativity and development within the field. Understand regional differences in pathogen ecology. The group discussed that considerable knowledge has been gained regarding the ecology -34-

35 of Lyme disease in the Northeastern and Midwestern United States, yet we know little about the natural history of the causative agent(s) in the southeastern states. Considerable work has been conducted on Borrelia spp. throughout several southeastern states but currently we understand little on the big picture of these organisms. Similarly, A. phagocytophilum appears to have dramatically different host ranges which may be related to variable strains circulating in nature. For example, raccoons are commonly infected with A. phagocytophilum in Connecticut but rarely show any evidence of infection in the southern states (Levin et al. 2002; Yabsley et al. 2008). Experiment studies with raccoons have indicated that different strains of A. phagocytophilum elicit variable infection dynamics (Yabsley et al. 2008). Furthermore, different species of endosymbionts may be present in certain geographic regions which may alter transmission of more pathogenic organisms by interference (e.g., some endosymbiotic SFGR can prevent establishment of pathogenic Rickettsia in vectors) (reviewed in Azad and Beard 1998). These are just a few of the many examples of regional differences in pathogens host range and transmission. Additionally, as host communities, habitat, or climate changes occur, the natural transmission cycle of a pathogen may be altered in historically common and well-studied regions. These differences can have a significant impact on the risk of human illness and further examination of even well-studied pathogens should be encouraged when they attempt to understand pathogen ecology in a novel geographic region or when habitat or climatic changes occur. Disclaimer The findings and conclusions of this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. -35-

36 References Cited Ammerman, N.C., Swanson, K.I., Anderson, J.M., Schwartz, T.R., Seaberg, E.C., Glass, G.E., and Norris, D.E Spotted fever group Rickettsia in Dermacentor variabilis, Maryland. Emerg. Infect. Dis. 10: Apperson, C.S., Engber, B, Nicholson, W.L., Mead, D.G., Engel, J., Yabsley, M.J., Dail, K, Johnson, J., and Watson, D.W Tick-borne diseases in North Carolina: is "Rickettsia amblyommii" a possible cause of rickettsiosis reported as Rocky Mountain spotted fever? Vector Borne Zoonot. Dis. 8: Azad, A., and Beard, C.B Rickettsial pathogens and their arthropod vectors. Emerg. Infect. Dis. 4: Billeter, S.A., Blanton, H.L., Little, S.E., Levy, M.G., and Breitschwerdt, E.B Detection of Rickettsia amblyommii in association with a tick bite rash. Vector Borne Zoonot. Dis. 7: Burgdorfer, W Ecological and epidemiological considerations of Rocky Mountain spotted fever and scrub typhus. Pp In Walker, D.H. (Ed.). The biology of rickettsial diseases. Vol.I. CRC Press, Boca Raton, FL. Burgdorfer, W., Adkins, Jr., T.R., and Priester, L.E Rocky Mountain spotted fever (tick-borne typhus) in South Carolina: an educational program and tick/rickettsial survey in 1973 and Am. J. Trop. Med. Hyg. 24: Burgdorfer, W, Cooney, J.C., and Thomas, L.A Zoonotic potential (Rocky Mountain spotted fever and tularemia) in the Tennessee Valley region. II. Prevalence of Rickettsia rickettsii and Francisella tularensis in mammals and ticks from Land Between the Lakes. Am. J. Trop. Med. Hyg. 23: Burgdorfer, W., Hayes, S.F., and Mavros, A.J. 1981a. Nonpathogenic rickettsiae in Dermacentor andersoni: a limiting factor for the distribution of Rickettsia rickettsii. Pp In Burgdorfer, W., and Anacker, R. (Eds.). Rickettsiae and rickettsial diseases. Academic Press, New York. Burgdorfer, W., Hayes, S.F., Thomas, L.A., and Lancaster, J.L. 1981b. A new spotted fever group rickettsia from the lone star tick, Amblyomma americanum. Pp In Burgdorfer, W., and Anacker, R. (Eds.). Rickettsiae and rickettsial diseases. Academic Press, New York. Chapman, A.S., Murphy, S.M., Demma, L.J., Holman, R.C., Curns, A.T., McQuiston, J.H., Krebs, J.W., and Swerdlow, D.L Rocky Mountain spotted fever in the United States, Vector Borne Zoonot. Dis. 6: Centers for Disease Control and Prevention Notice to readers: final 2008 reports of nationally notifiable infectious diseases. MMWR 58: ;

37 Dergousoff, S.J., Gajadhar, A.J.A., and Chilton, N.B Prevalence of Rickettsia species in Canadian populations of Dermacentor andersoni and D. variabilis. Appl. Environ. Microbiol. 75: Ellison, D.W., Clark, T.R., Sturdevant, D.E., Virtaneva, K., Porcella, S.F., and Hackstadt, T Genomic comparison of virulent Rickettsia rickettsii Sheila Smith and avirulent Iowa. Infect. Immun. 76: Gage, K.L., Schrumpf, M.E., Karstens, R.K., Burgdorfer, W., and Schwan, T.G DNA typing of rickettsiae in naturally infected ticks using a polymerase chain reaction/restriction fragment length polymorphism system. Am. J. Trop. Med. Hyg. 50: Graf, P.C.F., Chretien, J.P., Ung, L., Gaydos, J.C., and Richards, A.L Prevalence of seropositivity to spotted fever group rickettsiae and Anaplasma phagocytophilum in a large, demographically diverse U.S. sample. Clin. Infect. Dis. 46: Jiang J., Yarina, T., Miller, M.K., Stromdahl, E.Y., and Richards, A.L Molecular detection of Rickettsia amblyommii in Amblyomma americanum parasitizing humans. Vector Borne Zoonot. Dis. 10: Karpathy, S., Dasch, G.A., and Eremeeva, M.E Molecular typing of isolates of Rickettsia rickettsii by use of DNA sequencing of variable intergenic regions. J. Clin. Microbiol. 45: Labruna, M.B., Whitworth, T., Bouyer, D.H., McBride, J., Camargo, L.M. Camargo, E.P., Popov, V., and Walker, D.H Rickettsia belli and Rickettsia amblyommii in Amblyomma ticks from the State of Rondonia, Western Amazon, Brazil. J. Med. Entomol. 41: Labruna, M.B., Pacheco, R.C., Nava, S., Brandao, P.E., Richtzenhain, L.J., and Guglielmone, A.A Infection by Rickettsia belli and Candidatus Rickettsia amblyommii in Amblyomma neumanni ticks from Argentina. Microb. Ecol. 54: Levin, M.L., Nicholson, W.L., Massung, R.F., Sumner, J.W., and Fish, D Comparison of the reservoir competence of medium-sized mammals and Peromyscus leucopus for Anaplasma phagocytophilum in Connecticut. Vector Borne Zoonot. Dis. 2: Loving, S.M., Smith, A.B., Di Salvo, A.F., and Burgdorfer, W Distribution and prevalence of spotted fever group rickettsiae in ticks from South Carolina, with an epidemiological survey of persons bitten by infected ticks. Am. J. Trop. Med. Hyg. 27: Macaluso, K.R., and Azad, A.F Rocky Mountain spotted fever and other spotted fever group rickettsioses. Pp In Goodman, J. L., Dennis, D. T., and Sonenshine, D. E. (Eds.). Tick-borne diseases of humans. ASM Press, Washington, DC. Marshall, G.S., Stout, G.G., Jacobs, R.F., Shutze, G.E., Paxton, H., Buckingham, S.C., De Vincenzo, J.P., Jackson, M.A., San Jaoquin, V.H., Standaert, S.M., -37-

38 Woods, C.R., and The Tick-Borne Infections in Children Study (TICS) Group Antibodies reactive to Rickettsia rickettsii among children living in the southeast and south central regions of the United States. Arch. Pediatr. Adolesc. Med. 157: Mixson, T.R., Campbell, S.R., Gill, J.S., Ginsberg, H.S., Reichard, M.V., Schulze, T.L, and Dasch, G.A Prevalence of Ehrlichia, Borrelia, and rickettsial agents in Amblyomma americanum (Acari: Ixodidae) collected from nine states. J. Med. Entomol. 43: Munderloh, U.G., and Kurtti, T.J Cellular and molecular interrelationships between ticks and prokaryotic tick-borne pathogens. Annu. Rev. Entomol. 40: Nicholson, W.L., Masters, E., and Wormser, G.P Preliminary serologic investigation of Rickettsia amblyommii in the aetiology of Southern tick associated rash illness (STARI). Proc 5 th Intl Conf. on Rickettsiae and Rickettsial Diseases, Marseille, France, May 2008, Eur. Soc. Clin. Microbiol. Infect. Dis., CMI 15 (Suppl. 2): Oliver, Jr., J.H., Lin T., Gao L., Clark, K.L, Banks, C.W., Durden, L.A., James, A.M., and Chandler, Jr., F.W An enzootic transmission cycle of Lyme borreliosis spirochetes in the southeastern United States. Proc. Natl. Acad. Sci., U.S.A. 100: Oliver, Jr., J.H., Gao, L., and Lin, T Comparison of the spirochete Borrelia burgdorferi s. l. isolated from the tick Ixodes scapularis in southeastern and northeastern United States. J. Parasitol. 94: Paddock, C.D., Finley, R.W., Wright, C.S., Robinson, H.N., Schrodt, B.J., Lane, C.C., Ekenna, O., Blass, M.A., Tamminga, C.L., Ohl, C.A., McLellan, S.L.F., Goddard, J. Holman, R.C., Openshaw, J.J., Sumner, J.W., Zaki, S.R., and Eremeeva, M.E Rickettsia parkeri rickettsiosis and its clinical distinction from Rocky Mountain spotted fever. Clin. Infect. Dis. 47: Paddock, C.D., and Yabsley, M.J Ecological havoc, the rise of white tailed deer, and the emergence of Amblyomma americanum-associated zoonoses in the United States. Curr. Top. Microbiol. Immunol. 315: Paddock, C.D The science and fiction of emerging rickettsioses. Ann. N.Y. Acad. Sci. 1166: Parola P., Matsumoto, K., Socolovschi, C., Parzy, D., and Raoult, D A tick-borne rickettsia of the spotted-fever group, similar to Rickettsia amblyommii, in French Guyana. Ann. Trop. Med. Parasitol. 101: Philip, R.N., and Casper, E.A Serotypes of spotted fever group rickettsiae isolated from Dermacentor andersoni (Stiles) in western Montana. Am. J. Trop. Med. Hyg. 30:

39 Rudenko, N., Golovchenko, M., Lin, T., Gao, L., Grubhoffer, L., and Oliver, Jr., J.H Delineation of a new species of the Borrelia burgdorferi sensu lato complex, Borrelia americana sp. nov. J. Clin. Microbiol. 47: Smith, M.P., Ponnusamy, L., Jiang, J., Abu Ayyash, L., Richards, A.L., and Apperson, C.S Bacterial pathogens in ixodid ticks from a piedmont county in North Carolina: Prevalence of rickettsial organisms. Vector Borne Zoonot. Dis. 10: Stothard, D.R., and Fuerst, P.A Evolutionary analysis and the Spotted Fever and Typhus groups of Rickettsia using 16S rrna gene sequences. Syst. Appl. Microbiol. 18: Stromdahl, E.Y., Vince, M.A., Billingsley, P.M., Dobbs, N.A., and Williamson, P.C Rickettsia amblyommii infecting Amblyomma americanum larvae. Vector Borne Zoonot. Dis. 8: Sumner, J.W., Durden, L.D., Goddard, J., Stromdahl, E.Y., Clark, K.L., Reeves, W.K., and Paddock, C.D Gulf Coast ticks (Amblyomma maculatum) and Rickettsia parkeri, United States. Emerg. Infect. Dis.13: Wormser, E, Liveris, D., Nowakowski, J., Nadelman, R.B., Holmgren, D., Bittker, S., Cooper, D., Wang, G., and Schwartz, I Microbiologic evaluation of patients from Missouri with erythema migrans. Clin. Infect. Dis. 40: Yabsley, M.J., Murphy, S.M., Luttrell, M.P., Little, S.E., Massung, R.F., Stallknecht, D.E., Conti, L.A., Blackmore, C.G., and Durden, L.A Experimental and field studies on the suitability of raccoons (Procyon lotor) as hosts for tick-borne pathogens. Vector Borne Zoonot. Dis. 8:

40 Tick Bite Prevention and Tick Control Discussion leaders: Howard Ginsberg and Thomas Mather Focus group members: John Carroll, Emily Gutierrez-Zielinski, Joe Hope, Rosmarie Kelly, Jarrod Leland, Nolan Newton, Kirby Stafford, and Karen Yates Abstract The voluminous recent literature on tick bite prevention and tick control primarily covers management of Lyme disease in the northern U.S. and Europe, and tick control on cattle. Research is needed on tick management in the southern U.S. Priority research topics include geographical distribution of ticks and pathogens, attachment time required for transmission of pathogens important in the south, public knowledge and attitudes and ways to foster improved prevention, and effectiveness of repellents and other precautions, tick control methods, and IPM practices in southern environments. Information on ticks, associated pathogens, tick bite prevention, and tick control should be made available via websites (all such sites should be linked so that local information is readily obtainable). A tick management manual specific to southern ticks and environments should be produced. Kits for tick bite prevention should be made readily available and simple to use. An ASTHO (Association of State and Territorial Health Officials) or similar publication should be produced to provide guidance to localities on how to develop tick bite prevention and tick control programs. Introduction The scope of the Tick bite prevention and tick control group discussion was limited to ticks that affect humans, with only minor attention to ticks on domestic animals. The focus was on tick management for the purpose of preventing tickborne diseases. Several reviews of tick management techniques have been published in recent years (George et al. 2008; Ginsberg and Stafford 2005; Piesman and Eisen 2008; Samish et al. 2008; Sonenshine 2008; Stafford and Kitron 2002; Willadsen 2008). However, a constant theme of the discussion was that most of these techniques were developed to manage Ixodes scapularis and Lyme disease in the northeastern U.S., or cattle ticks and associated diseases in various parts of the world. However, their applicability to the important ticks in the southern U.S., notably Amblyomma americanum and Dermacentor variabilis, and associated diseases (Macaluso and Azad 2005; Goddard and Varela-Stokes 2009) has not been well evaluated. Furthermore, changing environmental conditions, potentially including changing roles of tick species such as A. maculatum, are not well understood. Baseline Information Needs -40-

41 Careful targeting of tick management efforts in the southern U.S. is essential because of the broad geographical area involved and the focal nature of tick distribution. Baseline information is needed on spatial and temporal distributional patterns of ticks and tick-borne pathogens to allow efficient allocation of resources devoted to tick management. Spatial distribution. Geographical data on tick and pathogen distribution are needed on coarse (county) and fine (community and habitat) scales. Countylevel data (Dennis et al. 1998) and standardized surveys (Diuk-Wasser et al. 2006) are available for Ixodes scapularis, but not for Amblyomma americanum or Dermacentor variabilis, which have major importance in the south. Statewide survey data are available for these species in some states (e.g., in Georgia, North Carolina, Tennessee, Virginia). Both active and passive surveys can provide useful information on geographical distribution of disease risk (Nicholson and Mather 1996; Johnson et al. 2004). Furthermore, geographic distribution data on human cases of reportable tick-borne diseases are compiled by the CDC. These data should be analyzed to provide overall distributional data on these tick species and associated pathogens, and knowledge gaps should be identified and filled. Temporal distribution. Phenologies of human-biting stages are broadly known for southern ticks, but location-specific information needs to be compiled to help target tick bite prevention and management efforts at disease foci. Phenology of I. scapularis is still not well characterized in the south. Time to transmission. Transmission of B. burgdorferi typically requires nearly two days of attachment by I. scapularis (Piesman et al. 1987). This delay in transmission has important implications for Lyme disease prevention practices. Transmission times of the primary southern tick-borne pathogens are less well known. Rickettsia rickettsii apparently requires several hours of D. variabilis attachment for transmission to humans (Macaluso and Azad 2005), but the temporal pattern has not been well characterized. Transmission times for other important rickettsiae, including Ehrlichia chaffeensis and Anaplasma phagocytophilum, are unknown. These transmission times should be determined to inform recommendations for personal precautions to avoid these diseases. Public knowledge, attitudes, practices. Diligent and appropriate application of tick bite prevention techniques and tick management methods are necessary for effective prevention of tick borne diseases. Studies at northern sites suggest some degree of compliance resulting from public education, but with limited efficacy at preventing tick bites (Poland 2001; Malouin et al. 2003). Research on current levels of public knowledge, attitudes toward ticks and practices for tick bite prevention is needed to effectively target public education programs. -41-

42 Tick bite prevention. Effective prevention of tick bites using personal precautions requires knowledge of the efficacies of various techniques for local tick species, and maximal use of these techniques by people at risk of tick exposure. Efficacy of available techniques. Many of the personal protection techniques currently recommended for Lyme disease prevention in the northern U.S. might be less effective in southern environments. For example, tucking pants into socks is likely to be more effective at avoiding I. scapularis bites because nymphs of this species quest near ground level and use a sedentary ambush approach to find hosts. Amblyomma americanum, in contrast, is a very active and fast moving tick that quests higher in vegetation, so it is less likely to be avoided using this precaution. Research is needed on the effectiveness of all standard black-legged tick avoidance methods to determine their effectiveness for avoidance of lone star ticks and American dog ticks. Repellents with active ingredients including deet, picaridin, and permethrin are commercially available, and other products are currently in development. There has been some study of the effectiveness of various repellents on southern species (e.g., Solberg et al. 1995; Carroll et al. 2005, 2008), but more research is needed to develop the knowledge required to make reliable recommendations about repellent use in the south. We recommend standardization of testing methods so that efficacies of existing and new repellents can be easily compared. The difference in prevalence of zoonotic pathogens in questing ticks between the northern states (where Borrelia burgdorferi is highly prevalent) and southern states (where the more virulent rickettsial pathogens tend to have low prevalence in ticks) have implications for the effectiveness of tick-bite protection for disease prevention. The implications of this difference need to be considered in order to optimize recommendations for avoiding tick-borne disease. No vaccines are currently available for tick-borne diseases of humans in the southern U.S. Current research programs on anti-tick vaccines and on vaccines to lower attachment success and pathogen transmission show considerable promise. Optimizing use of self-protection techniques. Attitudes and practices that relate to tick bite prevention vary considerably in different groups of people. For example, hunters tend to be aware of tick bite prevention methods and to utilize them, while people on summer picnics or short hikes in natural areas tend to be less conscientious about tick bite prevention. To effectively target public education programs to lower incidence of tick bite, research is needed on sociological and psychological factors that influence peoples knowledge, attitudes, and practices. Education needs to be targeted geographically and temporally, and using approaches that maximize compliance. Accurate and locally appropriate information, and any necessary tools and materials should be easy for ordinary people to obtain. -42-

43 We recommend that all websites that provide tick-related information include links to other major websites, and that it be made simple for users to click to websites with information specifically relevant to their local area. We also recommend developing relationships with retail outlets, including chain and local drugstores and outfitters, to provide tick-bite prevention materials (e.g., forceps appropriate for tick removal, repellents, and informational material) so that they are easily visible just before and during times of peak tick activity, affordable, and easy to use. Environmental modification. Habitat and host relations of A. americanum and D. variabilis have received substantial study (reviewed by Hair and Bowman 1986; Sonenshine 1993), and several investigators have evaluated the effects of environmental interventions on populations of these ticks. Environmental manipulations include controlled burns, removing canopy plants to promote desiccation by opening up ground-level vegetation to sunlight, low mowing of lawns and meadows, and lowering vertebrate host populations or excluding hosts (especially deer) by fencing. Environmental management can influence habitat suitability for ticks directly, or can influence tick abundance through its effects on host behavior (Presley and Hair 1988). Applicability of these techniques varies along the gradient from urban to suburban to rural to natural areas. For example, controlled burns have had moderate success at lowering numbers of D. variabilis (Smith et al. 1946) and A. americanum (Bloemer et al. 1990), but tick population recovery tends to be rapid, and this technique is not applicable in human residential areas. Knowledge of environmental factors that influence tick presence and abundance can be utilized to develop landscaping practices that lower tick numbers, or separate areas of human activity from areas of tick abundance. Combined use of mowing, fencing, wood-chip or crushed rock barriers, construction of decks and boardwalks, and placement of furniture and play areas can minimize tick-human contact, thus preventing tick-borne disease around the home and in playgrounds, etc. These techniques have been studied for I. scapularis in the north, to the point that detailed recommendations are available for practical implementation (Stafford 2007). However, effectiveness of these techniques likely differs for southern ticks and southern environments, so research is needed to adapt these techniques for implementation in the south. A manual similar to the one produced by the Connecticut Agricultural Experiment Station (Stafford 2007), adapted to southern ticks and environments would be immensely valuable for prevention of tick-borne disease in the southern states. Host-centered techniques. White tailed deer are important hosts for all active life stages of A. americanum (Childs and Paddock 2003), so manipulation of deer populations can potentially influence tick abundance. Exclusion of deer by fencing can be utilized in suburban environments, but efficacy at lowering A. americanum populations is modest (Bloemer et al. 1986, 1990; Ginsberg et al. -43-

44 2002a), and effectiveness depends on the size of the exclosure (Perkins et al. 2006). Deer exclusion can be integrated with other techniques to manage A. americanum (Bloemer et al. 1990). However, in some trials deer exclusion actually resulted in increased numbers of D. variabilis (Bloemer et al. 1986) and questing adult I. scapularis (Ginsberg and Zhiuoa 1999). Biological control. Numerous organisms kill ticks and could potentially be developed as biological control agents, including predators, parasites, and pathogens (Samish et al. 2008), but none is commercially applied for tick control at present. A product using the pathogenic fungus Metarhizium anisopliae is currently under development. This fungus is pathogenic to I. scapularis (Zhioua et al. 1997), as well as to some nontarget insect species (Ginsberg et al. 2002b), but its efficacy against A. americanum and D. variabilis has not been established. Pesticides. Area-wide pesticide applications. Broad scale pesticide applications for tick control are most effective when carefully targeted, because of the widespread but locally clumped nature of tick distributions (Goddard 1997). Pesticides can be applied to heavy-use areas, as in area-wide treatment of pastures for A. americanum control on cattle (Barnard et al. 1994), or can be targeted at yard edges in barrier applications to discourage tick movement into lawns (Stafford 2007). The need for appropriate targeting implies that pesticides should be applied by professional applicators rather than by homeowners. Research is needed on the effectiveness of area-wide and barrier applications at preventing tick bites in peridomestic and other human-use areas in the southern U.S. Targeted pesticide applications. Pesticides can be targeted at domestic animals using direct applications, such as by spraying cattle (Barnard and Jones 1981), or by applying via collars or spot applications to dogs and cats. Application to wild animals for area-wide tick management requires that enough of the local host animals are treated to attain successful control. Several devices have been developed to apply pesticides to small mammals, including bait boxes to control D. variabilis (Sonenshine and Haines 1985) and I. scapularis (Dolan et al. 2004) on rodents, and cardboard tubes containing pesticide-treated cotton balls to control I. scapularis on mice (Mather et al. 1987). Techniques to target acaricides at large mammals include the use of systemics (such as ivermectin) applied to deer via treated bait (Miller et al. 1989; Pound et al. 1996), and topical application of pesticides to deer using devices such as the 4-poster (Pound et al. 2000; Carroll et al. 2002). These techniques show promise, particularly for local control of A. americanum and I. scapularis, but efficacy in preventing tick bites in southern states has not been established. Integrated Pest Management (IPM). IPM programs for tick control can be oriented toward commodity protection using a traditional cost-benefit approach to management, or toward public health protection using a cost-efficiency approach to minimize the number of human cases of illness with a given level of resources -44-

45 (Ginsberg and Stafford 2005). Barnard et al. (1994) analyzed integrated management of A. americanum on cattle using a computer simulation model of lone star tick population dynamics (Haile and Mount 1987; Mount et al. 1993) to assess costs and benefits of different combinations of control methods. Bloemer et al. (1990) performed field tests of the effectiveness of different combinations of management methods to lower recreational exposure to A. americanum at Land Between the Lakes, in Kentucky and Tennessee. Additional studies of IPM programs for A. americanum and D. variabilis at high-risk southern sites would provide invaluable information to help managers design IPM programs for these ticks and associated pathogens. The ability of public health personnel to develop IPM programs for southern ticks would benefit greatly from a manual of tick management similar to the one produced by the Connecticut Agricultural Experiment Station for northern ticks (Stafford 2007), but oriented toward the tick species and environmental conditions in the southern states. Before this manual could be produced, a great deal of research is needed, as proposed earlier in this document, to provide information on the effectiveness of available tick management techniques in controlling southern tick species. We also recommend that a publication be produced for ticks and tick-borne diseases similar to the report by the Association of State and Territorial Health Officials that dealt with mosquitoes and West Nile Virus (ASTHO 2005). In particular, this publication should provide guidance to states and local communities on how to develop public health protection programs at levels appropriate for local needs and available funding (minimal programs, intermediate programs and comprehensive surveillance and management programs). Recommendations: Priority research needs include studies on: Geographical distribution of ticks and pathogen prevalence at coarse (county) and fine (community) scales. Time from initial tick attachment to pathogen transmission for pathogens common in southern states, especially rickettsiae. Levels of public knowledge, attitudes toward ticks, and practices for tick bite protection; sociological and psychological factors that influence these attitudes and practices. Effectiveness of personal protection and tick management techniques utilized in the northern states and elsewhere at controlling ticks in southern environments. Effectiveness of available repellents against southern tick species. IPM practices to prevent tick bites and tick-borne disease transmission. -45-

46 Priority actions: A central website with information about southern ticks, associated pathogens, self-protection, and practical management techniques should be established. All websites with tick-related information should link to this website and to other sites so that a person finding any of these websites can click to the central website as well as to a site with specific information relevant to their locale. A tick management manual, similar to that published by the Connecticut Agricultural Experiment Station for northern ticks (Stafford 2007) should be produced and made available online. Arrangements should be made with potential distributors (e.g., drug stores, outfitters) to provide a simple kit for sale that would be useful for protection from southern ticks (informational material, forceps suitable for tick removal, repellents, etc.). A publication similar to the ASTHO piece on mosquitoes and WNV should be produced to provide guidance to localities on developing tick bite and tick-borne disease prevention programs. References Cited ASTHO Public health confronts the mosquito. Association of State and Territorial Health Officials. Washington, DC. (available online at: Barnard, D.R., and Jones, B.G Field efficacy of acaricides for control of the lone star tick on cattle in southeastern Oklahoma. J. Econ. Entomol. 74: Barnard, D.R., Mount, G.A., Haile, D.G., and Daniels, E Integrated management strategies for Amblyomma americanum (Acari: Ixodidae) on pastured beef cattle. J. Med. Entomol. 31: Bloemer, S.R., Snoddy, E.L., Cooney, J.C., and Fairbanks, K Influence of deer exclusion on populations of lone star ticks and American dog ticks (Acari: Ixodidae). J. Econ. Entomol. 79: Bloemer, S.R., Mount, G.A., Morris, T.A., Zimmerman, R.H., Bernard, D.R., and Snoddy, E.L Management of lone star ticks (Acari: Ixodidae) in recreational areas with acaricide applications, vegetative management and exclusion of white-tailed deer. J. Med. Entomol. 27: Carroll, J.F., Allen, P.C., Hill, D.E., Pound, J.M., Miller, J.A., and, George, J.E Control of Ixodes scapularis and Amblyomma americanum through use of the 4-poster treatment device on deer in Maryland. Exp. Appl. Acarol. 28:

47 Carroll, J.F., Klun, J.A., and Debboun, M Repellency of deet and SS220 applied to skin involves olfactory sensing by two species of ticks. Med. Vet. Entomol. 19: Carroll, J.F., Benante, J.P., Klun, J.A., White, C.E., Debboun, M., Pound, J.M., and Dheranetra, W Twelve-hour duration testing of cream formulations of three repellents against Amblyomma americanum. Med. Vet. Entomol. 22: Childs, J.E., and Paddock, C.D The ascendency of Amblyomma americanum as a vector of pathogens affecting humans in the United States. Annu. Rev. Entomol. 48: Dennis, D.T., Nekomoto, T.S., Victor, J.C., Paul, W.S., and Piesman, J Reported distribution of Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae) in the United States. J. Med. Entomol. 35: Diuk-Wasser, M.A., Gatewood, A.G., Cortinas, M.R., Yaremych-Hamer, S., Tsao, J., Kitron, U., Hickling, G., Brownstein, J.S., Walker, E., Piesman, J., and Fish, D Spatiotemporal patterns of host-seeking Ixodes scapularis nymphs (Acari: Ixodidae) in the United States. J. Med. Entomol. 43: Dolan, M.C., Maupin, G.O., Schneider, B.S., Denatale, C., Hamon, N., Cole, C., Zeidner, N.S., and Stafford, III, K.C Control of immature Ixodes scapularis (Acari: Ixodidae) on rodent reservoirs of Borrelia burgdorferi in a residential community of southeastern Connecticut. J. Med. Entomol. 41: George, J.E., Pound, J.M., and Davey, R.B Acaricides for controlling ticks on cattle and the problem of acaricide resistance. Pp In Bowman, A.S., and Nuttall, P. (Eds.). Ticks: Biology, disease and control. Cambridge University Press. Cambridge, UK. Ginsberg, H.S., and Zhioua, E Influence of deer abundance on the abundance of questing adult Ixodes scapularis (Acari: Ixodidae). J. Med. Entomol. 36: Ginsberg, H.S., Butler, M., and Zhioua, E. 2002a. Effect of deer exclusion by fencing on abundance of Amblyomma americanum (Acari: Ixodidae) on Fire Island, New York, USA. J. Vector Ecol. 27: Ginsberg, H.S., LeBrun, R.A., Heyer, K., and Zhioua, E. 2002b. Potential nontarget effects of Metarhizium anisopliae (Deuteromycetes) used for biological control of ticks (Acari: Ixodidae). Environ. Entomol. 31: Ginsberg, H.S., and Stafford, III, K.C Management of ticks and tick-borne diseases. Pp In Goodman, J.L., Dennis, D.T., and Sonenshine, D.E. (Eds.). Tick-borne diseases of humans. ASM Press, Washington, D.C. Goddard, J Clustering effects of lone star ticks in nature: implications for control. J. Environ. Hlth. 59(10):

48 Goddard, J., and Varela-Stokes, A.S Role of the lone star tick, Amblyomma americanum (L.), in human and animal diseases. Vet. Parasitol. 160: Haile, D.G., and Mount, G.A Computer simulation of population dynamics of the lone star tick, Amblyomma americanum (Acari: Ixodidae). J. Med. Entomol. 24: Hair, J.A., and Bowman, J.L Behavioral ecology of Amblyomma americanum. Pp In Sauer, J.R. and Hair, J.A. (Eds.). Morphology, physiology, and behavioral biology of ticks. Wiley, NY. Johnson, J.L., Ginsberg, H.S., Zhioua, E., Whitworth, U.G., Markowski, D., Hyland, K.E., and Hu, R Passive tick surveillance, dog seropositivity, and incidence of human Lyme disease. Vector Borne Zoonot. Dis. 4: Macaluso, K.R., and Azad, A.F Rocky Mountain Spotted Fever and other spotted fever group rickettsioses. Pp In Goodman, J.L., Dennis, D.T., and Sonenshine, D.E. (Eds.). Tick-borne diseases of humans. ASM Press, Washington, DC. Malouin R., Winch, P., Leontsini, E., Glass, G., Simon, D., Hayes, E.B., and Schwartz, B.S Longitudinal evaluation of an educational intervention for preventing tick bites in an area with endemic Lyme disease in Baltimore County, Maryland. Am. J. Epidemiol. 157: Mather, T.N., Ribeiro, J.M.C., and Spielman, A Lyme disease and babesiosis: acaricide focused on potentially infected ticks. Am J. Trop. Med. Parasitol. 36: Miller, J.A., Garris, G. I., George, J.E., and Oehler, D.D Control of lone star ticks (Acari: Ixodidae) on Spanish goats and white-tailed deer with orally administered ivermectin. J. Econ. Entomol. 82: Mount, G.A., Haile, D.G., Barnard, D.R., and Daniels, E New version of LSTSIM for computer simulation of Amblyomma americanum (Acari: Ixodidae) population dynamics. J. Med. Entomol. 30: Nicholson, M.C., and Mather, T.N Methods for evaluating Lyme disease risks using Geographic Information Systems and geospatial analysis. J. Med. Entomol. 33: Perkins, S.E., Cattadori, I.M., Tagliapietra, V., Rizzoli, A.P., and Hudson, P.J Localized deer absence leads to tick amplification. Ecology 87: Piesman, J., and Eisen, L Prevention of tick-borne diseases. Annu. Rev. Entomol. 53: Piesman, J., Mather, T.N., Sinsky, R.J., and Spielman, A Duration of tick attachment and Borrelia burgdorferi transmission. J. Clin. Microbiol. 25:

49 Poland, G.A Prevention of Lyme disease: a review of the evidence. Mayo Clinic Proc. 76: Pound, J.M., Miller, J.A., George, J.E., Oehler, D.D., and Harmel, D.E Systemic treatment of white-tailed deer with ivermectin-medicated bait to control free-living populations of lone star ticks (Acari: Ixodidae). J. Med. Entomol. 33: Pound, J.M., Miller, J.A., and George, J.E Efficacy of amitraz applied to white-tailed deer by the '4-poster' topical treatment device in controlling freeliving lone star ticks (Acari: Ixodidae). J. Med. Entomol.37: Presley, S.M., and Hair, J.A Lone star tick (Acari: Ixodidae) management by host manipulation through habitat modification. J. Med. Entomol. 25: Samish, M., Ginsberg, H., and Glazer, I Anti-tick biological control agents: assessment and future perspectives. Pp In Bowman, A.S., and Nuttall, P. (Eds.). Ticks: Biology, disease and control. Cambridge University Press. Cambridge, UK. Smith, C.N., Cole, M.N., and Gouck, H.K Biology and Control of the American Dog Tick. U.S. Department of Agriculture Technical Bulletin pp. Solberg, V.B., Klein T.A., McPherson K.R., Bradford B.A., Burge J.R., and Wirtz, R.A Field evaluation of deet and a piperidine repellent (A ) against Amblyomma americanum (Acari: Ixodidae). J. Med. Entomol. 32: Sonenshine, D.E Biology of ticks, Vol. 2. Oxford University Press, NY. 465 pp. Sonenshine, D.E Pheromones and other semiochemicals of ticks and their use in tick control. Pp In Bowman, A.S. and Nuttall, P. (Eds.). Ticks: Biology, disease and control. Cambridge University Press. Cambridge, UK. Sonenshine, D.E., and Haines, G A convenient method for controlling populations of the American dog tick, Dermacentor variabilis (Acari:Ixodidae) in the natural environment. J. Med. Entomol. 22: Stafford, K.C., III Tick Management Handbook, Revised Edition. The Connecticut Agricultural Experiment Station, New Haven, CT. Stafford, K.C., III, and Kitron, U Environmental management for Lyme borreliosis control. Pp In Gray, J.S., Kahl, O., Lane, R.S., and Stanek, G. (Eds.). Lyme borreliosis: Biology, epidemiology and control. CABI Publishing, Oxon, UK. Willadsen, P Anti-tick vaccines. Pp In Bowman, A.S., and Nuttall, P. (Eds.). Ticks: Biology, disease and control. Cambridge University Press. Cambridge, UK. -49-

50 Zhioua, E., Browning, M., Johnson, P.W., Ginsberg, H.S., and LeBrun, R.A Pathogenicity of the entomopathogenic fungus Metarhizium anisopliae (Deuteromycetes) to Ixodes scapularis (Acari: Ixodidae). J. Parasitol. 83:

51 Institutional Policies and Inter-Agency Interactions Discussion leaders: Ben Beard and Daniel Strickman Focus group participants: Herb Bolton, Stan Cope, Susan Jennings, Rob Massung, Sam Perdue, Prasad Rao, Susan Ratcliffe, Pat Smith, Tracee Treadwell, David Wong Bottom Line Up Front The purpose of this institutional working group (IWG) was to examine how various institutions with an interest in reducing illness caused by tick-borne pathogens could work together to accomplish their missions. The details of the discussions are presented below, but the main product from the meeting was two action items. First, the IWG recommended establishment of a committee to write a tickborne diseases plan. The plan would make suggestions on how to reduce barriers between institutions in order to enhance the flow of information on ticks, their control, and the diseases associated with them. It would examine available human, facility, and monetary resources for the required research. The plan should also provide a mechanism for assessing the performance of the TBD community. Impact should include improvements in individual prevention of tick bites, treatment of individual residents for control of ticks, community-wide tick control, and public health functions with respect to TBDs (statistics, economics, identification of pathogens, outreach to physicians). Also of importance will be the identification of the communities concerned, whether stakeholders, researchers, or outreach specialists. The report would be improved by specific examples to illustrate its points, such as the scarce success stories with areawide tick control. It should be clear from the content of the report that TBDs are a target of the One Health strategy, in that wildlife are consistently involved in maintenance of the tick and/or the pathogen. Discussions in the report will contribute toward prioritization and timelines of research goals, based on their practical importance for preventing disease and on their feasibility. Finally, it would be useful for the plan to include an outline of interagency memoranda of understanding that would facilitate the work and bring some structure to relationships. The second action item was to improve outreach. This would include establishing a newsletter called Tick Talk. This newsletter would inform interested agencies and stakeholders about efforts in tick research and control. Hopefully, this format would provide more timely summaries and a forum for discussions that are not suitable in a peer-reviewed journal. In parallel to a newsletter, an interagency website would also help inform the community and it would provide a centralized location for accumulation of research results. It is -51-

52 possible that the modest funding for these efforts could be provided by US EPA or by the IPM Centers. Key Issues The need for better diagnostic tests for TBDs Diagnosis of disease in humans with suspected infections by tick-borne pathogens is a medical challenge for a number of reasons. First, the incidence of some TBD is generally low, greatly decreasing the index of suspicion and positive predictive value. Second, some of the etiological agents are taxonomically similar, creating the possibility of cross reaction between immunological tests. Third, the existing FDA-approved diagnostic tests are often serologic tests, which are of limited value during the acute phase of illness. Finally, the reagents (immune sera, antigens, primers) are not always available commercially or available widely for clinical laboratories. Even when diagnostic tests are developed, FDA approval and commercial availability can be very difficult to achieve. Consequently, the need for improved diagnostic tests is considered one of the greatest challenges to a better understanding of TBDs and their effective management. The need for formal training programs for vector-borne disease specialists Most professional personnel involved in TBDs were initially trained in a different field or were trained in a specialized aspect of vector or pathogen biology. As a result, there is a lack of personnel in research and practice who are able to assemble all the skills necessary to approach the problem in an integrated fashion. Practitioners in mosquito abatement districts, the military, and in public health learn the majority of their operational skills on the job. Training for licensing public health pesticide applicators in some states, and, especially, in the military, is helpful. No university-based program exists in the U.S. for broad training in control of vector-borne pathogens, combining science and operational skills. Such training would have to include a wide variety of subjects, but with focus on those skills that could be used in integrated vector management programs. For example, the training might provide general immunological background, but specific training on IFA, Western blot, and vaccination. The need for new acaricides and better methods for controlling ticks Tick control is small economically, which discourages manufacturers from developing new methods. Nonetheless, the desire by the public for better control of ticks on companion animals and the general enthusiasm for topical repellents has generated significant new products during the last 10 years. Specifically, new active ingredients in oral and pour-on products for cats and dogs have resulted in improvements in tick protection for those animals. New topical repellents (picaridin, IR3535, and p-menthane diol) have been introduced into the US market, though their efficacy against ticks is poorly documented. Major -52-

53 efforts by the USDA Agricultural Research Service, the Bill and Melinda Gates Foundation, and the US military to discover and develop new insecticides for public health use are resulting in candidate compounds with completely new modes of action, but these are, for the most part, years away from practical use. Wider screening of existing, registered toxicants could produce new acaricides that could be developed quickly. Is there a place for increasing the role of animal surveillance as it relates to human disease risk? The CDC assembles national statistics on human infection with selected pathogens and APHIS selectively monitors infections of agricultural animals, but there are few specific efforts to survey for human disease by examining animal populations. Examples include monitoring wild rodents for plague and hantavirus, as well as birds for influenza virus and West Nile virus. There might be a productive role for this kind of surveillance in order to assess risk of and document TBDs. How are TBD-related efforts coordinated and conveyed between federal and state agencies and other stakeholders? With the exception of professional conferences and targeted workshops like this one, coordination of stakeholders concerned with TBDs is very weak. Reportable disease like Lyme and RMSF create statistics that can result in measurable progress, but other TBDs are ignored. One very admirable effort is by the U.S. Army s Center for Health Promotion and Preventive Medicine (now the US Army Public Health Command [Provisional]). They conduct a program in coordination with medical facilities on military bases to gather ticks that have bitten humans. These ticks are tested by PCR for a wide variety of pathogens, resulting in a nation-wide data set. How does institutional policy (state and federal) translate down to the public level and affect services the public can receive for TBDs, including prevention, control, treatment and physician services? Information on tick-bite prevention and tick control is widely disseminated through local, state, and regional resources. Outside of official channels, there is much advice offered in association with commercial products, publications, and non-government organizations. The best information is based on primary and secondary references, though low-quality information is also common. Labels of products for tick control and tick-bite prevention are closely reviewed by the U.S. EPA, which is probably the system closest to translation of official policy to a public level. The military has a manual that includes directions on avoiding tick bites. Though the manual is freely available to the public, it is probably seldom used by the wider audience. Several books have been published on tick control and tick-bite prevention by reputable authors. CDC has a number of resources available at their website and distributed upon request, including a tick management handbook for home owners, distribution maps, and a prevention -53-

54 tool kit that contains trail signs, multi-lingual prevention brochures, fact sheets, web widgets, and radio PSAs. The printed documents are available in highresolution PDF format for download. Who is responsible for and empowered to control ticks and tick-borne disease? Tick control to protect humans is seldom undertaken by communities in the same manner as mosquito abatement. Some vector control districts include tick control in their mission, though their activities are usually restricted to identification, Lyme Borrelia determination, and advice. Although not for the protection of humans, the USDA Animal Plant Health and Inspection Service conducts an extensive program for control of the cattle fever tick in southern Texas. The military probably has the most organized approach, thanks to systematic evaluation of ticks from servicemen and their families and organized dissemination of control techniques (permethrin-treated uniforms). What unexplored or underutilized opportunities exist for interagency cooperative efforts in preventing and controlling TBDs? As a general consideration, those wishing to improve coordination between public and private entities that could contribute toward organized control of TBDs need to think about how the natural history of the pathogens intersects with various interests. For example, Lyme disease is strongly dependent on wild deer for maintenance of the Ixodes vectors. Interested parties include those tasked with direct patient care, recreational activities in parks and preserves, wildlife management, garden extension activities, diagnostic services, epidemiology, and pest control. Probably the most significant connection to make is between environmental services (i.e., those administered by public works) and health services. What other needs are currently not being addressed? The discussion above touches on the major issues of risk assessment, surveillance, control, and sustainability. Most activities, even in research, have been reactive rather than proactive. There is evidence that the TBD problem is getting worse, but the data to prove this are weak and assignment of cause has been difficult. Moving from assumption to evidence in this area would be very helpful in directing efforts to prevent expansion of TBDs. How can we better communicate between agencies? Meetings with clear focus like this one are very helpful, but the result has not been hopeful. Our group felt that the breadth of the discussion has to be national rather than regional and some members thought that expansion of the discussion to include veterinary problems would help achieve critical mass. A website and newsletter directed at government agencies would be very helpful for coordination and mutual awareness of opportunities and challenges. -54-

55 Workshop Participants Disease Surveillance, Laboratory Diagnosis, Case Reporting Discussion Leaders Hogrefe, Wayne Focus Diagnostics, Cypress, CA Nicholson, William Rickettsial Zoonoses Branch, CDC, Atlanta, GA Eremeeva, Marina Evans, Chris Garrison, Laurel Herman-Giddens, Marcia Krebs, John McQuiston, Jennifer Mock, Valerie Traeger, Marc Focus Group Participants Rickettsial Zoonoses Branch, CDC, Atlanta, GA South Carolina State Dept. of Hlth. & Environ. Control, Columbia Georgia State Dept. of Human Res., Div. Public Hlth., Atlanta Tick-Borne Infections Council of NC, Inc., Pittsboro, NC Rickettsial Zoonoses Branch, CDC, Atlanta, GA Rickettsial Zoonoses Branch, CDC, Atlanta, GA Bureau of Laboratories, Florida Dept. of Health, Jacksonville Indian Health Services, White River, AZ Tick Biology and Ecology Eisen, Becky Eisen, Lars Piesman, Joe Discussion Leaders Bacterial Diseases Branch, CDC, Fort Collins, CO Dept. Microbiology, Immunology & Pathol., Colo. St. Univ., Ft. Collins Bacterial Diseases Branch, CDC, Fort Collins, CO Focus Group Participants Apperson, Charles Dept. of Entomology, NC State University, Raleigh Durden, Lance Dept. of Biology, Georgia Southern University, Statesboro Gaines, David Virginia Dept. of Health, Richmond Hickling, Graham Center of Wildlife Health, Univ. of Tennessee, Knoxville -55-

56 Kitron, Uriel Dept. of Environmental Studies, Emory University, Atlanta, GA Pathogen Biology and Ecology Macaluso, Kevin Paddock, Chris Yabsley, Michael Breitschwerdt, Ed Clark, Kerry Dasch, Greg Johnson, Barbara Little, Susan Norris, Doug Richards, Al Stromdahl, Ellen Discussion Leaders Dept. of Pathobiological Sciences, Louisiana State Univ., Baton Rouge Infectious Diseases Pathology Branch, CDC, Atlanta, GA SE Cooperative Wildlife Disease Study, Univ. of Georgia, Athens Focus Group Participants Dept. of Clinical Sciences, NC State University, Raleigh Dept. of Public Health, University of North Florida, Jacksonville Rickettsial Zoonoses Branch, CDC, Atlanta, GA Bacterial Zoonoses Branch, CDC, Fort Collins, CO Dept. of Pathobiology, Oklahoma State Univ., Stillwater Dept. of Molecular Microbiology & Immunology, Johns Hopkins Univ., Baltimore, MD Rickettsial Diseases Dept., Naval Medical Research Center, Silver Spring, MD US Army Ctr. Health Prom. Prev. Med., Aberdeen Proving Grnd., MD Tick Bite Prevention and Tick Control Ginsberg, Howard Mather, Tom Discussion Leaders USGS Patuxent Wildlife Res Cntr, Univ. of Rhode Island, Kingston Center for Vector-Borne Diseases, Univ. of Rhode Island, Kingston Focus Group Participants Carroll, John USDA, ARS, Beltsville, MD Gutierrez-Zielinski, Emily CDC, DVBID, Fort Collins, CO -56-

57 Hope, Joe Bayer Environmental Science, Research Triangle, NC Kelly, Rosmarie Georgia State Dept. of Health, Atlanta Leland, Jarrod Novozymes Biologicals, Salem, VA Newton, Nolan Dept. Environ. Natural Resources, Public Health Pest Management Section, Raleigh, NC Stafford, Kirby Dept. of Entomology, Connecticut Agricultural Experiment Station, New Haven Yates, Karen Missouri Health Department, Jefferson City Institutional Policies and Inter-Agency Interactions Beard, Ben Strickman, Dan Discussion Leaders Bacterial Diseases Branch, CDC, Fort Collins, CO USDA, ARS, Veterinary, Medical, & Urban Entomology, Beltsville, MD Focus Group Participants Bolton, Herb USDA, CSREES, Arlington, VA Cope, Stan Armed Forces Pest Management Board, Silver Spring, MD Jennings, Susan EPA, Athens, GA Massung, Rob Rickettsial Zoonoses Branch, CDC, Atlanta, GA Perdue, Sam NIAID, NIH, Bethesda, MD Rao, Prasad FDA, Rockville, MD Ratcliffe, Susan North Central IPM Center, University of Illinois, Urbana, IL Smith, Pat Lyme Disease Assoc., Inc., Jackson, NJ Treadwell, Tracee CDC/CCID/NCZVED, Atlanta, GA Williams, Carl NC Division of Public Health, Raleigh, NC Wong, David National Park Service, Albuquerque, NM -57-

58 Regional Workshop to Assess Research and Outreach Needs in Integrated Pest Management to Reduce the Incidence of Tick-Borne Diseases in the Southern US held in the Tom Harkin Global Communication Center Centers for Disease Control and Prevention 1600 Clifton Road Atlanta, Georgia January 21-23,