Kiersten J. Kugeler

Incidence of Clinician-Diagnosed Lyme Disease, United States, 2005-2010.

Extrapolation from a large medical claims database suggests that 329,000 cases occur annually.

Molecular Epidemiology of Francisella tularensis in the United States

BACKGROUND In the United States, tularemia is caused by Francisella tularensis subsps. tularensis (type A) and holarctica (type B). Molecular subtyping has further divided type A into 2 subpopulations, A1 and A2. Significant mortality differences were previously identified between human infections caused by A1 (14%), A2 (0%) and type B (7%). To verify these findings and to further define differences among genotypes, we performed a large-scale molecular epidemiologic analysis of F. tularensis isolates from humans and animals. METHODS Pulsed-field gel electrophoresis with PmeI was performed on 302 type A and 61 type B isolates. Pulsed-field gel electrophoresis pattern and epidemiologic analyses were performed. Logistic regression was used to assess factors associated with human mortality. RESULTS Pulsed-field gel electrophoresis typing identified 4 distinct type A genotypes, A1a, A1b, A2a, and A2b, as well as type B. Genotypic and geographic divisions observed among isolates from humans were mirrored among isolates from animals, specifically among animal species that are linked to human infection and to enzootic maintenance of tularemia. Significant differences between human infections caused by different genotypes were identified with respect to patient age, site of organism recovery, and mortality. Human infections due to A1b resulted in significantly higher mortality (24%) than those caused by A1a (4%), A2 (0%), and type B (7%). CONCLUSIONS Three type A genotypes, A1a, A1b, and A2, were shown to be epidemiologically important. Our analysis suggests that A1b strains may be significantly more virulent in humans than A1a, A2, or type B strains. These findings have important implications for disease progression, disease prevention, and basic research programs.

Geographic Distribution and Expansion of Human Lyme Disease, United States.

Lyme disease occurs in specific geographic regions of the United States. We present a method for defining high-risk counties based on observed versus expected number of reported human Lyme disease cases. Applying this method to successive periods shows substantial geographic expansion of counties at high risk for Lyme disease.

Discrimination between Francisella tularensis and Francisella-like endosymbionts when screening ticks by PCR.

ABSTRACT The presence of Francisella-like endosymbionts in tick species known to transmit tularemia poses a potential diagnostic problem for laboratories that screen tick samples by PCR for Francisella tularensis. Tick samples initially considered positive for F. tularensis based on standard 16S rRNA gene PCR were found to be positive only for Francisella-like endosymbionts using a multitarget F. tularensis TaqMan assay (ISFtu2, tul4, and iglC) and 16S rRNA gene sequencing. Specificity of PCR-based diagnostics for F. tularensis should be carefully evaluated with appropriate specimen types prior to diagnostic use.

Clinical Recognition and Management of Tularemia in Missouri: A Retrospective Records Review of 121 Cases

BACKGROUND Clinical recognition of tularemia is essential for prompt initiation of appropriate antibiotic treatment. Although fluoroquinolones have desirable attributes as a treatment option, limited data on efficacy in the US setting exist. METHODS To define the epidemiology of tularemia in Missouri, and to evaluate practices and outcomes of tularemia management in general, we conducted a detailed retrospective review and analysis of clinical records for patients reported to the state from 2000 to 2007. RESULTS We reviewed records of 121 of 190 patients (64%) reported with tularemia; 79 (65%) were males; the median age was 37 years. Most patients presented with ulceroglandular (37%) and glandular (25%) forms of tularemia, followed by pneumonic (12%), typhoidal (10%), oculoglandular (3%), and oropharyngeal (2%) forms. Most cases (69%) were attributed to tick bites. Median incubation period was 3 days (range, 1-9 days), and patients sought care after a median of 3 days of illness (range, 0-44 days). Systemic disease occurred more commonly in older patients. Patients were prescribed tetracyclines (49%), aminoglycosides (47%), and fluoroquinolones (41%). Nine of 10 patients treated with ciprofloxacin for ≥10 days recovered uneventfully, without accompanying aminoglycosides or tetracyclines. CONCLUSIONS Tularemia is frequently initially misdiagnosed. A thorough exposure history, particularly for tick bites, and awareness of clinical features may prompt clinicians to consider tularemia and facilitate appropriate testing. Promising success with oral fluoroquinolones could provide an acceptable alternative to intravenous aminoglycosides or long courses of tetracyclines where clinically appropriate.

Epidemiology of Human Plague in the United States, 1900–2012

Epidemiologic changes reflect shifts in the populations at risk, the advent of effective therapy, and improved detection methods.

Isolation and Characterization of a Novel Francisella sp. from Human Cerebrospinal Fluid and Blood

ABSTRACT We describe the isolation of a Francisella sp. from normally sterile sites in acutely ill patients in two different states within 2 years. Microbiologic and molecular analyses indicate that this organism represents a novel Francisella sp. Clinicians and microbiologists should be aware of this new potential pathogen, as infection may be more common than recognized.

The frequency of genes encoding three putative group B streptococcal virulence factors among invasive and colonizing isolates

BackgroundGroup B Streptococcus (GBS) causes severe infections in very young infants and invasive disease in pregnant women and adults with underlying medical conditions. GBS pathogenicity varies between and within serotypes, with considerable variation in genetic content between strains. Three proteins, Rib encoded by rib, and alpha and beta C proteins encoded by bca and bac, respectively, have been suggested as potential vaccine candidates for GBS. It is not known, however, whether these genes occur more frequently in invasive versus colonizing GBS strains.MethodsWe screened 162 invasive and 338 colonizing GBS strains from different collections using dot blot hybridization to assess the frequency of bca, bac and rib. All strains were defined by serotyping for capsular type, and frequency differences were tested using the Chi square test.ResultsGenes encoding the beta C protein (bac) and Rib (rib) occurred at similar frequencies among invasive and colonizing isolates, bac (20% vs. 23%), and rib (28% vs. 20%), while the alpha (bca) C protein was more frequently found in colonizing strains (46%) vs, invasive (29%). Invasive strains were associated with specific serotype/gene combinations.ConclusionNovel virulence factors must be identified to better understand GBS disease.

Ecological Niche Modeling of Francisella tularensis Subspecies and Clades in the United States

Two subspecies of Francisella tularensis are recognized: F. tularensis subsp. tularensis (type A) and F. tularensis subsp. holartica (type B). Type A has been subdivided further into A1a, A1b, and A2, which differ geographically and clinically. The aim of this work was to determine whether or not differences among subspecies and clades translate into distinct ecological niches. We used 223 isolates from humans and wildlife representing all six genotypes (type A, B, A1, A2, A1a, or A1b). Ecological-niche models were built independently for each genotype, using the genetic algorithm for rule-set prediction. The resulting models were compared using a non-parametric multivariate analysis-of-variance method. A1 and A2 are ecologically distinct, supporting the previously observed geographic division, whereas ecological niches for types A and B overlapped notably but A1a and A1b displayed no appreciable differences in their ecological niches.

Canine Serology as Adjunct to Human Lyme Disease Surveillance

To better define areas of human Lyme disease risk, we compared US surveillance data with published data on the seroprevalence of Borrelia burgdorferi antibodies among domestic dogs. Canine seroprevalence >5% was a sensitive but nonspecific marker of human risk, whereas seroprevalence <1% was associated with minimal risk for human infection.