Holly M. Frost

Ecology and Epidemiology of Lyme Borreliosis

Lyme borreliosis is a zoonotic, tick-borne disease that infects humans worldwide. The disease is currently recognized as the most common vector-borne disease in Europe and North America. Disease is caused by several genospecies of the Borrelia burgdorferi sensu lato complex. Humans are at high risk of infection in regions where highly competent reservoirs are the primary hosts for the subadult stages of the tick, in contrast to regions where less competent or refractory animals feed ticks. Human infections are also most frequently associated with spring and summer months when the nymph stage of the tick is active.

Blastomyces Antigen Detection for Diagnosis and Management of Blastomycosis

ABSTRACT Blastomyces spp. antigen testing was evaluated over a 10-year period in an area where blastomycosis is endemic. Antigen testing was less sensitive than previously reported, but serial urine testing was useful in monitoring disease resolution or progression. Culture and cytopathology remain the gold standard for diagnosis and exclusion of this infection.

Blastomycosis in Children: An Analysis of Clinical, Epidemiologic, and Genetic Features

Background Blastomyces spp. are endemic in regions of the United States and result in blastomycosis, a serious and potentially fatal infection. Little is known about the presentation, clinic course, epidemiology, and genetics of blastomycosis in children. Methods A retrospective review of children with blastomycosis confirmed by culture or cytopathology between 1999 and 2014 was completed. Blastomyces sp. isolates were genotyped by using microsatellite typing, and species were typed by sequencing of internal transcribed spacer 2 (its2). Results Of the 114 children with blastomycosis identified, 79% had isolated pulmonary involvement and 21% had extrapulmonary disease. There were more systemic findings, including fever (P = .01), poor intake (P = .01), elevated white blood cell count (P < .01), and elevated C-reactive protein level (P < .01), in children with isolated pulmonary disease than in children with extrapulmonary disease. Children with extrapulmonary disease had more surgeries (P = .01) and delays in diagnosis (P < .01) than those with isolated pulmonary infection. Of 52 samples genotyped, 48 (92%) were Blastomyces gilchristii and 4 (8%) were Blastomyces dermatitidis. Conclusion This is the first large-scale study of the clinical, epidemiologic, and genetic features of blastomycosis in children. The majority of the children had isolated pulmonary disease with systemic findings. Patients with extrapulmonary disease were less likely to have systemic symptoms or additional laboratory evidence of infection, which made delays in diagnosis more common. More than 90% of the pediatric cases were caused by B gilchristii.

Serologic Evidence of Powassan Virus Infection in Patients with Suspected Lyme Disease1

Powassan virus (POWV) lineage II is an emerging tickborne flavivirus with an unknown seroprevalence in humans. In a Lyme disease–endemic area, we examined the seroreactivity to POWV in 2 patient cohorts and described the clinical features of the POWV-seroreactive patients. POWV disease might be less neuroinvasive than previously thought.

Risk Factors for Severe Infection, Hospitalization, and Prolonged Antimicrobial Therapy in Patients with Babesiosis

Babesiosis is an emerging tick-borne disease transmitted by the hard tick Ixodes scapularis, which also transmits Lyme disease. Better gradation of prognostic indicators are needed to determine which patients may develop serious complications requiring hospitalization, and to provide early guidance on appropriate therapy. In this study, we evaluated 128 patients with smear or real time polymerase chain reaction-confirmed Babesia microti infections over a period of 16 years. Patients with asplenia or immunocompromising conditions were more likely to have severe infection (P < 0.01), require hospitalization (P < 0.01), or receive prolonged courses of antimicrobials (P < 0.01). Nausea or vomiting (P < 0.01) and diarrhea (P < 0.01) along with hyperbilirubinemia (P < 0.01) were predictive of severe infection, hospitalization, and prolonged antimicrobial therapy. Patients with concurrent Lyme disease were less likely to require hospitalization and had similar severity of disease and length of antibiotic treatment compared with those without Lyme disease.

Evidence of delayed dissemination or re-infection with Blastomyces in two immunocompetent hosts.

Relapse or recurrence of blastomycosis in patients is rare. Re-infection of a patient with blastomycosis has not been previously reported. In this report, we describe relapse or reinfection with Blastomyces in 2 immunocompetent patients. This is the first study in which genetic typing was performed on paired Blastomyces isolates from the same patient obtained months apart.

Development and Validation of a Serologic Test Panel for Detection of Powassan Virus Infection in U.S. Patients Residing in Regions Where Lyme Disease Is Endemic

Approximately 100 cases of POWV disease were reported in the United States over the past 10 years. Most cases have occurred in the Northeast (52) and Great Lakes (45) regions (https://www.cdc.gov/powassan/statistics.html). The prevalence of POWV in ticks and mammals is increasing, and POWV poses an increasing threat in a greater geographical range. In areas of the Northeast and Midwest where Lyme disease is endemic, POWV testing is recommended for patients with a recent tick bite, patients with Lyme disease who have been treated with antibiotics, or patients with a tick exposure who have tested negative for Lyme disease or other tick-borne illnesses and have persistent symptoms consistent with posttreatment Lyme disease. Testing could also benefit patients with tick exposure and unexplained neurologic symptoms and chronic fatigue syndrome (CFS) patients with known tick exposure. Until now, diagnostic testing for Powassan virus has not been commercially available and has been limited to patients presenting with severe, neurologic complications. The lack of routine testing for Powassan virus in patients with suspected tick-borne disease means that little information is available regarding the overall prevalence of the virus and the full spectrum of clinical symptoms associated with infection. As Ixodes scapularis is the tick vector for Powassan virus and multiple other tick-borne pathogens, including the Lyme disease bacterium, Borrelia burgdorferi, the clinical presentations and long-term outcomes of Powassan virus infection and concurrent infection with other tick-borne disease pathogens remain unknown. ABSTRACT Powassan virus (POWV) is an emerging tick-borne arbovirus presenting a public health threat in North America. POWV lineage II, also known as deer tick virus, is the strain of the virus most frequently found in Ixodes scapularis ticks and is implicated in most cases of POWV encephalitis in the United States. Currently, no commercial tests are available to detect POWV exposure in tick-borne disease (TBD) patients. We describe here the development and analytical validation of a serologic test panel to detect POWV infections. The panel uses an indirect enzyme immunoassay (EIA) to screen. EIA-positive samples reflex to a laboratory-developed, POWV-specific immunofluorescence assay (IFA). The analytical sensitivity of the test panel was 89%, and the limit of detection was a plaque reduction neutralization test (PRNT) titer of 1:20. The analytical specificity was 100% for the IgM assay and 65% for the IgG assay when heterologous-flavivirus-positive samples were tested. On samples collected from regions where Lyme disease is endemic, seroprevalence for POWV in TBD samples was 9.4% (10 of 106) versus 2% when tested with non-TBD samples (2 of 100, P = 0.034). No evidence of POWV infection was seen in samples collected from a region where Lyme disease was not endemic (0 of 22). This test panel provides a sensitive and specific platform for detecting a serologic response to POWV early in the course of infection when neutralizing antibodies may not be detectable. Combined with clinical history, the panel is an effective tool for identifying acute POWV infection. IMPORTANCE Approximately 100 cases of POWV disease were reported in the United States over the past 10 years. Most cases have occurred in the Northeast (52) and Great Lakes (45) regions (https://www.cdc.gov/powassan/statistics.html). The prevalence of POWV in ticks and mammals is increasing, and POWV poses an increasing threat in a greater geographical range. In areas of the Northeast and Midwest where Lyme disease is endemic, POWV testing is recommended for patients with a recent tick bite, patients with Lyme disease who have been treated with antibiotics, or patients with a tick exposure who have tested negative for Lyme disease or other tick-borne illnesses and have persistent symptoms consistent with posttreatment Lyme disease. Testing could also benefit patients with tick exposure and unexplained neurologic symptoms and chronic fatigue syndrome (CFS) patients with known tick exposure. Until now, diagnostic testing for Powassan virus has not been commercially available and has been limited to patients presenting with severe, neurologic complications. The lack of routine testing for Powassan virus in patients with suspected tick-borne disease means that little information is available regarding the overall prevalence of the virus and the full spectrum of clinical symptoms associated with infection. As Ixodes scapularis is the tick vector for Powassan virus and multiple other tick-borne pathogens, including the Lyme disease bacterium, Borrelia burgdorferi, the clinical presentations and long-term outcomes of Powassan virus infection and concurrent infection with other tick-borne disease pathogens remain unknown.

Clinical Presentation and Outcomes of Children With Human Granulocytic Anaplasmosis

Background Adults with the tick-borne disease human granulocytic anaplasmosis (HGA) have a spectrum of acute febrile illnesses that, if untreated, might be severe. Clinical presentation and outcomes of children with HGA have been poorly described. Methods A retrospective analysis was conducted to determine the frequency, presentation, and outcomes of pediatric patients with HGA between 1994 and 2015 in a region of Wisconsin in which HGA is highly endemic. Patients with related International Classification of Diseases Ninth and Tenth Revision (ICD-9 and ICD-10, respectively) codes or positive HGA laboratory test results were evaluated and classified as having had confirmed, probable, or suspected HGA on the basis of the Centers for Disease Control and Prevention (CDC) case definition. The Fishers exact and Wilcoxon rank-sum tests were used in statistical comparisons. Results Of 187 children identified with possible HGA, 17 (9%) had confirmed, 75 (40%) had probable, and 91 (49%) had suspected infections. The number of cases rose sharply in 2010 and has remained between 16 and 36 cases per year since that time. A minority of children with confirmed or probable infections had elevated liver transaminase levels (33%), leukopenia (24%), thrombocytopenia (17%), or anemia (8%); 6 (7%) of these children required hospitalization. Children with evidence of concurrent HGA and Lyme disease (27% of confirmed or probable cases) had a higher risk of hospitalization (odds ratio, 6.55 [95% confidence interval, 1.11-38.78]). None of these children had life-threatening disease or died. Conclusions Evidence suggests that the frequency of HGA in children is increasing. Although most children had mild disease, doxycycline remains the treatment of choice, because outcome data for children without treatment remains limited.