Seroepidemiologic study of human infections with spotted fever group Rickettsiae in North Carolina.

Increasing entomologic and epidemiologic evidence suggests that spotted fever group rickettsiae (SFGR) other than Rickettsia rickettsii are responsible for spotted fever rickettsioses in the United States. A retrospective seroepidemiologic study was conducted on stored acute- and convalescent-phase sera that had been submitted for Rocky Mountain spotted fever testing to the North Carolina State Laboratory of Public Health. We evaluated the serologic reactivity of the paired sera to R. rickettsii, Rickettsia parkeri, and Rickettsia amblyommii antigens. Of the 106 eligible pairs tested, 21 patients seroconverted to one or more antigens. Cross-reactivity to multiple antigens was observed in 10 patients, and seroconversions to single antigens occurred in 11 patients, including 1 against R. rickettsii, 4 against R. parkeri, and 6 against R. amblyommii. Cross-absorption of cross-reactive sera and/or Western blots identified two presumptive cases of infection with R. parkeri, two presumptive cases of infection with R. rickettsii, and one presumptive case of infection with R. amblyommii. These findings suggest that species of SFGR other than R. rickettsii are associated with illness among North Carolina residents and that serologic testing using R. rickettsii antigen may miss cases of spotted fever rickettsioses caused by other species of SFGR.

Monitoring and Evaluation of Patient Engagement in Health Product Research and Development: Co-Creating a Framework for Community Advisory Boards.

PURPOSE: While patient engagement is becoming more customary in developing health products, its monitoring and evaluation to understand processes and enhance impact are challenging. This article describes a patient engagement monitoring and evaluation (PEME) framework, co-created and tailored to the context of community advisory boards (CABs) for rare diseases in Europe. It can be used to stimulate learning and evaluate impacts of engagement activities. METHODS: A participatory approach was used in which data collection and analysis were iterative. The process was based on the principles of interactive learning and action and guided by the PEME framework. Data were collected via document analysis, reflection sessions, a questionnaire, and a workshop. RESULTS: The tailored framework consists of a theory of change model with metrics explaining how CABs can reach their objectives. Of 61 identified metrics, 17 metrics for monitoring the patient engagement process and short-term outcomes were selected, and a "menu" for evaluating long-term impacts was created. Example metrics include "Industry representatives' understanding of patients' unmet needs;" "Feeling of trust between stakeholders;" and "Feeling of preparedness." "Alignment of research programs with patients' needs" was the highest-ranked metric for long-term impact. CONCLUSIONS: Findings suggest that process and short-term outcome metrics could be standardized across CABs, whereas long-term impact metrics may need to be tailored to the collaboration from a proposed menu. Accordingly, we recommend that others adapt and refine the PEME framework as appropriate. The next steps include implementing and testing the evaluation framework to stimulate learning and share impacts.

Association between lone star tick bites and increased alpha-gal sensitization: evidence from a prospective cohort of outdoor workers.

BACKGROUND: Alpha-gal is an oligosaccharide implicated in delayed anaphylaxis following red meat consumption. Exposure to tick bites has been correlated with development of an allergic response to alpha-gal. However, evidence prospectively linking exposure to a single tick species and an immune response to alpha-gal is lacking. METHODS: We used serum samples from a prior study cohort of outdoor workers in North Carolina, USA, with high exposure to the lone star tick, Amblyomma americanum, to prospectively evaluate the relationship between tick bites and anti-alpha-gal IgE antibodies. RESULTS: Individuals who reported exposure to one or more tick bites were significantly more likely to have a positive change in anti-alpha-gal IgE compared to individuals with no reported tick bites. This relationship was not dependent on time. A trend toward increasing number of tick bites and increased anti-alpha-gal IgE levels was observed but not statistically significant. CONCLUSION: To our knowledge, this is the first study to prospectively link documented exposure to A. americanum bites and increased sensitization to alpha-gal in a cohort of outdoor workers. Our results support the role of A. americanum as likely agents for eliciting an allergic response to red meat, and highlight the importance of preventing tick bites.

Incident Tick-Borne Infections in a Cohort of North Carolina Outdoor Workers.

Tick-borne diseases cause substantial morbidity throughout the United States, and North Carolina has a high incidence of spotted fever rickettsioses and ehrlichiosis, with sporadic cases of Lyme disease. The occupational risk of tick-borne infections among outdoor workers is high, particularly those working on publicly managed lands. This study identified incident tick-borne infections and examined seroconversion risk factors among a cohort of North Carolina outdoor workers. Workers from the North Carolina State Divisions of Forestry, Parks and Recreation, and Wildlife (n = 159) were followed for 2 years in a randomized controlled trial evaluating the effectiveness of long-lasting permethrin-impregnated clothing. Antibody titers against Rickettsia parkeri, Rickettsia rickettsii, "Rickettsia amblyommii," and Ehrlichia chaffeensis were measured at baseline (n = 130), after 1 year (n = 82), and after 2 years (n = 73). Titers against Borrelia burgdorferi were measured at baseline and after 2 years (n = 90). Baseline seroprevalence, defined as indirect immunofluorescence antibody titers of 1/128 or greater, was R. parkeri (24%), R. rickettsii (19%), "R. amblyommii" (12%), and E. chaffeensis (4%). Incident infection was defined as a fourfold increase in titer over a 1-year period. There were 40 total seroconversions to at least one pathogen, including R. parkeri (n = 19), "R. amblyommii" (n = 14), R. rickettsii (n = 9), and E. chaffeensis (n = 8). There were no subjects whose sera were reactive to B. burgdorferi C6 antigen. Thirty-eight of the 40 incident infections were subclinical. The overall risk of infection by any pathogen during the study period was 0.26, and the risk among the NC Division of Forest Resources workers was 1.73 times that of workers in other divisions (95% confidence interval [CI]: 1.02, 2.92). The risk of infection was lower in subjects wearing permethrin-impregnated clothing, but not significantly (risk ratio = 0.81; 95% CI: 0.47, 1.39). In summary, outdoor workers in North Carolina are at high risk of incident tick-borne infections, most of which appear to be asymptomatic.

Long-Lasting Permethrin-Impregnated Clothing Protects Against Mosquito Bites in Outdoor Workers.

Outdoor exposure to mosquitoes is a risk factor for many diseases, including malaria and dengue. We have previously shown that long-lasting permethrin-impregnated clothing protects against tick and chigger bites in a double-blind randomized controlled trial in North Carolina outdoor workers. Here, we evaluated whether this clothing is protective against mosquito bites by measuring changes in antibody titers to mosquito salivary gland extracts. On average, there was a 10-fold increase in titer during the spring and summer when mosquito exposure was likely to be the highest. During the first year of the study, the increase in titer in subjects wearing treated uniforms was 2- to 2.5-fold lower than that of control subjects. This finding suggests that long-lasting permethrin-impregnated clothing provided protection against mosquito bites.

Prevalence of Rickettsiales in ticks removed from the skin of outdoor workers in North Carolina.

BACKGROUND: Tick-transmitted rickettsial diseases, such as ehrlichiosis and spotted fever rickettsiosis, are significant sources of morbidity and mortality in the southern United States. Because of their exposure in tick-infested woodlands, outdoor workers experience an increased risk of infection with tick-borne pathogens. As part of a double blind randomized-controlled field trial of the effectiveness of permethrin-treated clothing in preventing tick bites, we identified tick species removed from the skin of outdoor workers in North Carolina and tested the ticks for Rickettsiales pathogens. METHODS: Ticks submitted by study participants from April-September 2011 and 2012 were identified to species and life stage, and preliminarily screened for the genus Rickettsia by nested PCR targeting the 17-kDa protein gene. Rickettsia were further identified to species by PCR amplification of 23S-5S intergenic spacer (IGS) fragments combined with reverse line blot hybridization with species-specific probes and through cloning and nucleotide sequence analysis of 23S-5S amplicons. Ticks were examined for Ehrlichia and Anaplasma by nested PCR directed at the gltA, antigen-expressing gene containing a variable number of tandem repeats, 16S rRNA, and groESL genes. RESULTS: The lone star tick (Amblyomma americanum) accounted for 95.0 and 92.9% of ticks submitted in 2011 (n = 423) and 2012 (n = 451), respectively. Specimens of American dog tick (Dermacentor variabilis), Gulf Coast tick (Amblyomma maculatum) and black-legged tick (Ixodes scapularis) were also identified. In both years of our study, 60.9% of ticks tested positive for 17-kDa. "Candidatus Rickettsia amblyommii", identified in all four tick species, accounted for 90.2% (416/461) of the 23S-5S-positive samples and 52.9% (416/787) of all samples tested. Nucleotide sequence analysis of Rickettsia-specific 23S-5S IGS, ompA and gltA gene fragments indicated that ticks, principally A. americanum, contained novel species of Rickettsia. Other Rickettsiales, including Ehrlichia ewingii, E. chaffeensis, Ehrlichia sp. (Panola Mountain), and Anaplasma phagocytophilum, were infrequently identified, principally in A. americanum. CONCLUSIONS: We conclude that in North Carolina, the most common rickettsial exposure is to R. amblyommii carried by A. americanum. Other Rickettsiales bacteria, including novel species of Rickettsia, were less frequently detected in A. americanum but are relevant to public health nevertheless.

Long-lasting permethrin impregnated uniforms: A randomized-controlled trial for tick bite prevention.

BACKGROUND: Because of frequent exposure to tick habitats, outdoor workers are at high risk for tick-borne diseases. Adherence to National Institute for Occupational Safety and Health-recommended tick bite prevention methods is poor. A factory-based method for permethrin impregnation of clothing that provides long-lasting insecticidal and repellent activity is commercially available, and studies are needed to assess the long-term effectiveness of this clothing under field conditions. PURPOSE: To evaluate the protective effectiveness of long-lasting permethrin impregnated uniforms among a cohort of North Carolina outdoor workers. DESIGN, SETTING, AND PARTICIPANTS: A double-blind RCT was conducted between March 2011 and September 2012. Subjects included outdoor workers from North Carolina State Divisions of Forestry, Parks and Recreation, and Wildlife who worked in eastern or central North Carolina. A total of 159 volunteer subjects were randomized, and 127 and 101 subjects completed the first and second years of follow-up, respectively. INTERVENTION: Uniforms of participants in the treatment group were factory-impregnated with long-lasting permethrin whereas control group uniforms received a sham treatment. Participants continued to engage in their usual tick bite prevention activities. MAIN OUTCOME MEASURES: Incidence of work-related tick bites reported on weekly tick bite logs. RESULTS: Study subjects reported 1,045 work-related tick bites over 5,251 person-weeks of follow-up. The mean number of reported tick bites in the year prior to enrollment was similar for both the treatment and control groups, but markedly different during the study period. In our analysis conducted in 2013, the effectiveness of long-lasting permethrin impregnated uniforms for the prevention of work-related tick bites was 0.82 (95% CI=0.66, 0.91) and 0.34 (95% CI=-0.67, 0.74) for the first and second years of follow-up. CONCLUSIONS: These results indicate that long-lasting permethrin impregnated uniforms are highly effective for at least 1 year in deterring tick bites in the context of typical tick bite prevention measures employed by outdoor workers.

Pilot study assessing the effectiveness of long-lasting permethrin-impregnated clothing for the prevention of tick bites.

INTRODUCTION: Tick-borne diseases such as Lyme disease, Rocky Mountain spotted fever, and ehrlichiosis are a significant concern for many thousands of workers who have frequent and unavoidable exposure to tick-infested habitats. Many North Carolina state employees with outdoor occupations report multiple tick bites each year, indicating that existing tick preventive strategies may be underutilized or ineffective. Treatment of clothing with permethrin, a nontoxic chemical with insecticidal, knockdown, and repellent properties, is highly effective against ticks. However, most permethrin products must be reapplied after several washings to maintain insecticidal activity. Recently, a factory-based method for long-lasting permethrin impregnation of clothing has been developed by Insect Shield, Inc., that allows clothing to retain insecticidal activity for over 70 washes. METHODS: A nonrandomized open label pilot study was conducted to determine the effectiveness of Insect Shield-treated clothing for the prevention of tick bites among 16 outdoor workers from the North Carolina Division of Water Quality under actual field conditions. Participants completed questionnaires at the start of follow-up (March, 2008) and at the end of follow-up (September, 2008), and tick bites and outdoor work hours were reported on weekly tick bite logs for the entire follow-up period. RESULTS: Subjects wearing Insect Shield-treated clothing had a 93% reduction (p < 0.0001) in the total incidence of tick bites compared to subjects using standard tick bite prevention measures. CONCLUSION: This study provides preliminary evidence that long-lasting permethrin-impregnated clothing may be highly effective against tick bites.

Practice-Based Research Network Partnership with CDC to acquire clinical specimens to study the etiology of southern tick-associated rash illness (STARI).

INTRODUCTION: Erythema migrans (EM) is an annular, erythematous, expanding rash that is characteristic of early Lyme disease. In the southern United States, however, many cases of EM seem to have an etiology different from that of Lyme disease. This little-understood condition is called Southern tick-associated rash illness. METHODS: With the goal of obtaining biological specimens and clinical histories from 12 to 20 STARI patients for use in etiologic research, microbiologists from the Centers for Disease Control and Prevention contacted the North Carolina Network Consortium, a statewide consortium of practice-based research networks. This article describes the methods by which the North Carolina Network Consortium successfully identified and enrolled Southern tick-associated rash illness patients into a primary care-based research protocol. RESULTS: A total of 23 patients were enrolled, with 100% attainment of the desired specimens. After an initial lack of success, the revised protocol identified and trained physicians practicing in endemic areas for the illness, used a coordinator with 24-hour availability, recruited participants using newspaper notices and medical providers, and provided regular reminders and progress updates. CONCLUSIONS: A practice-based research network can help basic scientists identify patients and collect specimens for clinically relevant research.