Tularemia Clinical Manifestations, Antimicrobial Treatment, and Outcomes: An Analysis of US Surveillance Data, 2006-2021.

BACKGROUND: Tularemia, a potentially fatal zoonosis caused by Francisella tularensis, has been reported from nearly all US states. Information on relative effectiveness of various antimicrobials for treatment of tularemia is limited, particularly for newer classes such as fluoroquinolones. METHODS: Data on clinical manifestations, antimicrobial treatment, and illness outcome of patients with tularemia are provided voluntarily through case report forms to the US Centers for Disease Control and Prevention by state and local health departments. We summarized available demographic and clinical information submitted during 2006-2021 and evaluated survival according to antimicrobial treatment. We grouped administered antimicrobials into those considered effective for treatment of tularemia (aminoglycosides, fluoroquinolones, and tetracyclines) and those with limited efficacy. Logistic regression models with a bias-reduced estimation method were used to evaluate associations between antimicrobial treatment and survival. RESULTS: Case report forms were available for 1163 US patients with tularemia. Francisella tularensis was cultured from a clinical specimen (eg, blood, pleural fluid) in approximately half of patients (592; 50.9%). Nearly three-quarters (853; 73.3%) of patients were treated with a high-efficacy antimicrobial. A total of 27 patients (2.3%) died. After controlling for positive culture as a proxy for illness severity, use of aminoglycosides, fluoroquinolones, and tetracyclines was independently associated with increased odds of survival. CONCLUSIONS: Most US patients with tularemia received high-efficacy antimicrobials; their use was associated with improved odds of survival regardless of antimicrobial class. Our findings provide supportive evidence that fluoroquinolones are an effective option for treatment of tularemia.

Changes in Emergency Medical Services Before and During the COVID-19 Pandemic in the United States, January 2018-December 2020.

BACKGROUND: As a result of the continuing surge of coronavirus disease 2019 (COVID-19), many patients have delayed or missed routine screening and preventive services. Medical conditions, such as coronary heart disease, mental health issues, and substance use disorder, may be identified later, leading to increases in patient morbidity and mortality. METHODS: National Emergency Medical Services Information System data were used to assess 911 emergency medical services (EMS) activations during 2018-2020. For specific activation types, the percentage of total activations was calculated per week, and Joinpoint analysis was used to identify changes over time. RESULTS: Since March 2020, the number of 911 EMS activations has decreased, while the percentages of on-scene death, cardiac arrest, and opioid use/overdose EMS activations were higher than prepandemic levels. During the early pandemic period, percentages of total EMS activations increased for on-scene death (from 1.3% to 2.4% during weeks 11-15), cardiac arrest (from 1.3% to 2.2% during weeks 11-15), and opioid use/overdose (from 0.6% to 1.1% during weeks 8-18). The percentages then declined but remained above prepandemic levels through calendar week 52. CONCLUSIONS: The COVID-19 pandemic has indirect consequences, such as relative increases in EMS activations for cardiac events and opioid use/overdose, possibly linked to disruptions is healthcare access and health-seeking behaviors. Increasing telehealth visits and other opportunities for patient-provider touch points for chronic disease and substance use disorders that emphasize counseling, preventive care, and expanded access to medications can disrupt delayed care-seeking during the pandemic and potentially prevent premature death.

The Specificity of the Persistent IgM Neutralizing Antibody Response in Zika Virus Infections among Individuals with Prior Dengue Virus Exposure.

Dengue viruses (DENV) and Zika virus (ZIKV) are related mosquito-borne flaviviruses with similar disease manifestations, vector ecologies, and geographic ranges. The ability to differentiate these viruses serologically is vital due to the teratogenic nature of ZIKV and the potential confounding of preexisting cross-reactive anti-DENV antibodies. Here, we illustrate the kinetics of the IgM neutralizing antibody (NAb) response using longitudinal samples ranging from acute ZIKV infection to late convalescence from individuals with evidence of prior DENV infection. By serially depleting antibody isotypes prior to the neutralization assay, we determined that IgM contributes predominantly to ZIKV neutralization and is less cross-reactive than the IgG NAb. The IgM NAb peaked around 14 days (95% confidence interval [95% CI], 13 to 15) and had a median duration of 257 days (95% CI, 133 to 427). These results demonstrate the persistence of IgM NAb after ZIKV infection and imply its potential role in diagnosis, vaccine evaluation, serosurveillance, and research on flavivirus-host interactions.

Performance of Dengue Diagnostic Tests in a Single-Specimen Diagnostic Algorithm.

BACKGROUND: Anti-dengue virus (DENV) immunoglobulin M (IgM) seroconversion has been the reference standard for dengue diagnosis. However, paired specimens are rarely obtained, and the interval for this testing negates its usefulness in guiding clinical case management. The presence of DENV viremia and appearance of IgM during the febrile phase of dengue provides the framework for dengue laboratory diagnosis by using a single serum specimen. METHODS: Archived paired serum specimens (n = 1234) from patients with laboratory-confirmed dengue from 2005 through 2011 were used to determine the diagnostic performance of real-time reverse transcription polymerase chain reaction (RT-PCR), for detection of DENV serotypes 1-4, and enzyme-linked immunosorbent assays (ELISAs), for detection of DENV nonstructural protein 1 (NS1) antigen and anti-DENV IgM. RESULTS: During 1-3 days after illness onset, real-time RT-PCR and NS1 antigen testing detected 82%-69% and 90%-84% of cases, respectively, as viremia levels declined, while anti-DENV IgM ELISA detected 5%-41% of cases as antibody appeared. Over the 10-day period of the febrile phase of dengue, the cumulative effect of using these 3 types of tests in a diagnostic algorithm confirmed ≥90% of dengue cases. CONCLUSIONS: The use of molecular or NS1 antigen tests to detect DENV and one to detect anti-DENV IgM in a single serum specimen collected during the first 10 days of illness accurately identified ≥90% of dengue primary and secondary cases.

Effect of a Dengue Clinical Case Management Course on Physician Practices in Puerto Rico.

BACKGROUND: Prior to 2010, the clinical management of dengue in Puerto Rico was inconsistent with World Health Organization guidelines. A 4-hour classroom-style course on dengue clinical management was developed in 2009 and mandated for Puerto Rico medical licensure in 2010. Fifty physicians were trained as "master trainers" and gave this course to 7638 physicians. This study evaluated the effect of the course on the clinical management of hospitalized dengue patients. METHODS: Pre- and post-course test responses were compared. Changes in physician practices were assessed by reviewing medical records of 430 adult and 1075 pediatric dengue patients at the 12 hospitals in Puerto Rico that reported the most cases during 2008-2009 (pre-intervention) and 2011 (post-intervention). Mixed-effects logistic regression was used to compare key indicators of dengue management. RESULTS: Physician test scores increased from 48% to 72% correct. Chart reviews showed that the percentage of adult patients who did not receive corticosteroids increased from 30% to 68% (odds ratio [OR], 5.9; 95% confidence interval [CI], 3.7-9.5) and from 91% to 96% in pediatric patients (OR, 2.7; 95% CI, 1.5-4.9). Usage of isotonic intravenous saline during the critical period increased from 57% to 90% in adult patients (OR, 6.2; 95% CI, 1.9-20.4) and from 25% to 44% in pediatric patients (OR, 3.4; 95% CI, 2.2-5.3). CONCLUSIONS: Management of dengue inpatients significantly improved following implementation of a classroom-style course taught by master trainers. An online version of the course was launched in 2014 to expand its reach and sustainability.

Probable and possible transfusion-transmitted dengue associated with NS1 antigen-negative but RNA confirmed-positive red blood cells.

BACKGROUND: In the absence of active blood donation screening, dengue viruses (DENV) have been implicated in only a limited number of transfusion transmissions worldwide. This study attempted to identify if blood from donors testing negative by an NS1-antigen (Ag) enzyme-linked immunosorbent assay (ELISA) but confirmed positive for DENV RNA caused DENV-related disease in recipients during the epidemic years of 2010 to 2012 in Puerto Rico. STUDY DESIGN AND METHODS: Donation aliquots testing negative by an investigational NS1-Ag ELISA were stored frozen and retested retrospectively using a research transcription-mediated amplification assay (TMA) detecting DENV RNA. All RNA-reactive donations were subject to confirmatory RNA and antibody testing. Recipient tracing was conducted for all components manufactured from TMA-reactive components. Medical chart review, recipient interview, and follow-up sampling occurred for 42 recipients transfused with TMA-reactive components. RESULTS: Six of 42 recipients developed new-onset fever in the 2 weeks posttransfusion; three (50%) received RNA confirmed-positive, NS1-Ag-negative red blood cell (RBC) units. One recipient of a high-titer unit (7 × 10(7) DENV-4 RNA copies/mL) developed severe dengue, and a second recipient had only fever recorded but had a negative sepsis work-up. New fever attributable to DENV infection in a third recipient was confounded by fever potentially attributable to posttransfusion sepsis. CONCLUSIONS: In our retrospective study, NS1-Ag detected 20% of all RNA confirmed-positive donations demonstrating limitations of NS1-Ag ELISA for blood donation screening. We identified one recipient with a clinical syndrome compatible with severe dengue who had received an NS1-Ag-negative but RNA confirmed-positive RBC unit. This investigation illustrates the difficulty in confirming transfusion transmission in dengue-endemic areas among severely ill transfusion recipients.

A Simple Modification to the Mosquito Homogenization Protocol Safely Inactivates West Nile Virus and Allows Virus Detection by the Rapid Analyte Measurement Platform (RAMP®) ASSAY.

We evaluated the ability of the Rapid Analyte Measurement Platform (RAMP(®)) mosquito-grinding buffer to inactivate West Nile virus (WNV) by subjecting WNV-positive samples ground in RAMP buffer to incubation intervals ranging from 5 min to 60 min. At each time point an aliquot was removed and serially diluted in bovine albumin (BA)-1 cell culture media to stop the inactivation process by RAMP buffer. Each BA-1 sample was tested for viable virus using Vero 6-well cell culture plaque assay and observed for plaques. We observed very limited inactivation of WNV (1-2 log10 plaque-forming units/ml) by RAMP buffer. Concerned for RAMP operators who may be using this assay in low-level biocontainment facilities, we developed an alternate sample homogenization protocol using Triton X-100 detergent that ensures complete WNV inactivation without compromising the performance of the RAMP assay.

Evaluation of a rapid analyte measurement platform and real-time reverse-transcriptase polymerase chain reaction assay West Nile virus detection system in mosquito pools.

We evaluated the commercially available Rapid Analyte Measurement Platform (RAMP) West Nile virus (WNV) antigen detection test for sensitivity and consistency with real-time reverse transcriptase polymerase chain reaction (RT-PCR) confirmation testing. Panels of samples consisting of WNV-spiked mosquito pools and negative control pools were sent to 20 mosquito abatement districts (MADs) that processed the pools using the RAMP assay. The samples were then sent to the reference laboratories used by the MADs for confirmation by real-time RT-PCR. Positive pools with virus titers of roughly 1-3 log10 PFU/ml had RAMP scores above the RAMP test positive cutoff score of 30 RAMP units, but these virus-positive samples could not be reliably confirmed by real-time RT-PCR testing. Pools with virus titers > or =4 log10 PFU/ml scored > or =50 RAMP units. Real-time RT-PCR results varied among the confirmation laboratories. With few exceptions, pools returning a RAMP score of > or =100 were confirmed with real-time RT-PCR, while pools returning a RAMP score of 50-99 appeared to be at the limit of real-time RT-PCR detection. Therefore, we recommend using a positive cutoff of 50 RAMP units with no real-time RT-PCR confirmation to maximize speed, efficiency, and economy of the RAMP assay. A more conservative approach would be to implement a "gray zone" range of 50-100 RAMP units. Pools scoring within the gray zone could be submitted for real-time RT-PCR confirmation with the understanding that positive pools may not confirm due to the inhibitory effect of the RAMP buffer on the real-time RT-PCR assay. We also conducted a series of experiments using laboratory-prepared mosquito pools spiked with WNV to compare mosquito homogenization buffers, pool sizes, and grinding methods in order to determine how these variables affect the RAMP and real-time RT-PCR assay results.

Enhancing Eastern Equine Encephalitis Virus Surveillance in New Jersey: Optimized Collection of Culiseta melanura.

Eastern equine encephalitis virus (EEEV) causes the most clinically severe neuroinvasive arboviral disease in the United States. The virus is endemic in eastern and Gulf Coast states and the Great Lakes region, causing cases annually. To detect EEEV circulation in its enzootic cycle before the virus infects humans and other mammals, mosquito control agencies in New Jersey have conducted mosquito surveillance using a series of permanent wooden resting box sites since 1975. We conducted 2 field studies, 1 evaluating resting traps and 1 evaluating efficacy of CO2 lures, to optimize collection of Culiseta melanura, the primary enzootic vector of EEEV. Resulting mosquito samples were subjected to molecular analysis to determine EEEV infection rates. Corrugated plastic boxes trapped more bloodfed Cs. melanura than other resting trap types (resting boxes, Centers for Disease Control and Prevention [CDC] resting traps, or fiber pots) and were similar to resting boxes in total number of female Cs. melanura caught. Further, non-baited CDC light traps were more successful in trapping host-seeking Cs. melanura than those baited with dry ice, a CO2 lure. The EEEV RNA was identified in Cs. melanura, Aedes vexans, Anopheles quadrimaculatus, and Uranotaenia sapphirina. Our findings indicate that corrugated plastic boxes and non-CO2 baited traps could improve detection of Cs. melanura. Mosquito control agencies are encouraged to periodically assess their surveillance strategy for EEEV.

Culex flavivirus and West Nile virus in Culex quinquefasciatus populations in the southeastern United States.

Little is known of the interactions between insect-only flaviviruses and other arboviruses in their mosquito hosts, or the potential public health significance of these associations. The specific aims of this study were to describe the geographic distribution, prevalence, and seasonal infection rates of Culex flavivirus (CxFV) and West Nile virus (WNV) in Culex quinquefasciatus Say in the Southeastern United States, investigate the potential association between CxFV and WNV prevalence in Cx. quinquefasciatus and describe the phylogenetic relationship among CxFV and WNV isolates from the Southeastern United States and around the world. Using ArboNET records, 11 locations were selected across Georgia, Mississippi, and Louisiana that represented a range of WNV human case incidence levels. Cx. quinquefasciatus were trapped weekly throughout the summer of 2009 and pools were screened for flavivirus RNA by reverse transcriptase polymerase chain reaction. Cx. quinquefasciatus from Georgia had significantly higher CxFV infection rates than either Mississippi or Louisiana. CxFV was not detected in Mississippi after July, and no CxFV was detected in Cx. quinquefasciatus in Louisiana. In Georgia, CxFV infection rates were variable between and within counties and over time. WNV infection rates were not significantly different across states or months, and WNV sequences from all three states were identical to each other in the envelope and NS5 gene regions. Phylogenetically, NS5 and E gene sequences from Georgia CxFV isolates clustered with CxFV from Japan, Iowa, and Texas. Multiple CxFV genetic variants were found circulating simultaneously in Georgia. No evidence was found supporting an association between WNV and CxFV infection prevalence in Cx. quinquefasciatus.

Potential quantitative effect of a laboratory-based approach to Lyme disease surveillance in high-incidence states.

Historically, public health surveillance for Lyme disease has required clinical follow-up on positive laboratory reports for the purpose of case classification. In areas with sustained high incidence of the disease, this resource-intensive activity yields a limited benefit to public health practice. A range of burden-reducing strategies have been implemented in many states, creating inconsistencies that limit the ability to decipher trends. Laboratory-based surveillance, or surveillance based solely on positive laboratory reports without follow-up for clinical information on positive laboratory reports, emerged as a feasible alternative to improve standardization in already high-incidence areas. To inform expectations of a laboratory-based surveillance model, we conducted a retrospective analysis of Lyme disease data collected during 2012-2018 from 10 high-incidence states. The number of individuals with laboratory evidence of infection ranged from 1302 to 20,994 per state and year. On average, 55% of those were ultimately classified as confirmed or probable cases (range: 29%-86%). Among all individuals with positive laboratory evidence, 18% (range: 2%-37%) were determined to be 'not a case' upon investigation and 23% (range: 2%-52%) were classified as suspect cases due to lack of associated clinical information and thus were not reported to the Centers for Disease Control and Prevention (CDC). The number of reported cases under a laboratory-based approach to surveillance in high-incidence states using recommended two-tier testing algorithms is likely to be, on average, 1.2 times higher (range: 0.6-1.8 times) than what was reported to CDC during 2012-2018. A laboratory-based surveillance approach for high-incidence states will improve standardization and reduce burden on public health systems, allowing public health resources to focus on prevention messaging, exploration of novel prevention strategies and alternative data sources to yield information on the epidemiology of Lyme disease.

Exposure of Domestic Cats to Three Zoonotic Bartonella Species in the United States.

Cat-associated Bartonella species, which include B. henselae, B. koehlerae, and B. clarridgeiae, can cause mild to severe illness in humans. In the present study, we evaluated 1362 serum samples obtained from domestic cats across the U.S. for seroreactivity against three species and two strain types of Bartonella associated with cats (B. henselae type 1, B. henselae type 2, B. koehlerae, and B. clarridgeiae) using an indirect immunofluorescent assay (IFA). Overall, the seroprevalence at the cutoff titer level of ≥1:64 was 23.1%. Seroreactivity was 11.1% and 3.7% at the titer level cutoff of ≥1:128 and at the cutoff of ≥1:256, respectively. The highest observation of seroreactivity occurred in the East South-Central, South Atlantic, West North-Central, and West South-Central regions. The lowest seroreactivity was detected in the East North-Central, Middle Atlantic, Mountain, New England, and Pacific regions. We observed reactivity against all four Bartonella spp. antigens in samples from eight out of the nine U.S. geographic regions.

Prevention of Lyme and other tickborne diseases using a rodent-targeted approach: A randomized controlled trial in Connecticut.

Tickborne diseases are an increasing public health problem in the northeastern USA. Bait boxes that apply acaricide to rodents have been shown in small field studies to significantly reduce abundance of Ixodes scapularis ticks as well as their pathogen infection rates in treated areas. The effectiveness of this intervention for preventing human tickborne diseases (TBDs) has not been demonstrated. During 2012-2016, TickNET collaborators conducted a randomized, blinded, placebo-controlled trial among 622 Connecticut households. Each household received active (containing fipronil wick) or placebo (empty) bait boxes in their yards over two consecutive years. Information on tick encounters and TBDs among household members was collected through biannual surveys. Nymphal ticks were collected from a subset of 100 properties during spring at baseline, during treatment, and in the year post-intervention. Demographic and property characteristics did not differ between treatment groups. There were no significant differences post-intervention between treatment groups with respect to tick density or pathogen infection rates, nor for tick encounters or TBDs among household members. We found no evidence that rodent-targeted bait boxes disrupt pathogen transmission cycles or significantly reduce household risk of tick exposure or TBDs. The effectiveness of this intervention may depend on scale of use or local enzootic cycles.

Development of diagnostic microsphere-based immunoassays for Heartland virus.

BACKGROUND: Heartland virus (HRTV), a recently reclassified member of the genus Bandavirus, family Phenuiviridae, was first isolated in 2009 from a Missouri farmer exhibiting leukopenia and thrombocytopenia with suspected ehrlichiosis. Since then, more HRTV cases have been diagnosed, and firstline laboratory diagnostic assays are needed to identify future infections Objectives. We sought to develop rapid and reliable IgM and IgG microsphere immunoassays (MIAs) to test sera of patients suspected of having HRTV infection, and to distinguish between recent and past infections. STUDY DESIGN: Heartland virus antigen was captured by an anti-HRTV monoclonal antibody covalently bound to microspheres. Antibodies in human sera from confirmed HRTV-positive and negative cases were reacted with the microsphere complexes and detected using a BioPlex® 200 instrument. Assay cutoffs were determined by receiver operator characteristic analysis of the normalized test output values, equivocal zones for each assay were defined, and sensitivities, specificities, accuracies, and imprecision values were calculated. RESULTS: Sensitivities, specificities and accuracies of the IgM and IgG MIAs were all >95 %. Both tests were precise within and between assay plates, and cross-reactivity with other arboviruses was not observed. CONCLUSIONS: HRTV IgM and IgG MIAs are accurate and rapid first-line methods to serologically identify recent and past HRTV infections.

Mycoplasma detection in a historical arbovirus repository: Commercial kit comparison and implications for improved repository management.

The Centers for Disease Control and Prevention, Arbovirus Reference Collection (ARC) contains viral isolates from both environmental and human sources that are maintained in the laboratory through passage in suckling mouse brain and/or vertebrate and invertebrate cell culture. There has been increased concern regarding the effect of mycoplasma contamination on virus growth and its impact on research and phenotypic analysis. Therefore, quality control testing of virus preparations has become a routine part of the ARC quality assurance program. We compared the performance of three kits - the PCR Mycoplasma Detection Kit (ABM), the VenorGem Mycoplasma Detection Kit (Sigma), and the MycoAlert Mycoplasma Detection Kit (Lonza) - against a reference mycoplasma detection assay from the American Tissue Culture Collection (ATCC) using 744 virus preparations in the ARC, representing 721 unique viruses comprising twelve families and unclassified viruses. We found the ABM kit had the highest sensitivity and specificity, followed by the Sigma kit and Lonza kit, when compared to the ATCC kit. An increase in false positives was observed for the Lonza kit for preparations recently passaged in suckling mouse. Our data supports previously reported observations; that once introduced a specific species of mycoplasma is maintained within a lab.

Evaluation of Patient IgM and IgG Reactivity Against Multiple Antigens for Improvement of Serodiagnostic Testing for Early Lyme Disease.

Serologic testing is the standard for laboratory diagnosis and confirmation of Lyme disease. Serodiagnostic assays to detect antibodies against Borrelia burgdorferi, the agent of Lyme borreliosis, are used for detection of infection. However, serologic testing within the first month of infection is less sensitive as patients' antibody responses continue to develop. Previously, we screened several B. burgdorferi in vivo expressed antigens for candidates that elicit early antibody responses in patients with Stage 1 and 2 Lyme disease. We evaluated patient IgM seroreactivity against 6 antigens and found an increase in sensitivity without compromising specificity when compared to current IgM second-tier immunoblot scoring. In this study, we continued the evaluation using a multi-antigen panel to measure IgM plus IgG seroreactivity in these early Lyme disease patients' serum samples. Using two statistical methods for calculating positivity cutoff values, sensitivity was 70 and 84-87%, for early acute and early convalescent Lyme disease patients, respectively. Specificity was 98-100% for healthy non-endemic control patients, and 96-100% for healthy endemic controls depending on the statistical analysis. We conclude that improved serologic testing for early Lyme disease may be achieved by the addition of multiple borrelial antigens that elicit IgM and IgG antibodies early in infection.

Performance of InBios ZIKV Detect™ 2.0 IgM Capture ELISA in two reference laboratories compared to the original ZIKV Detect™ IgM Capture ELISA.

ZIKV Detect™ 2.0 IgM Capture ELISA (InBios International, Seattle, WA) recently replaced the ZIKV Detect™ IgM Capture ELISA and a number of significant changes have been made to the original version. This study compares data generated from the ZIKV Detect™ 2.0 IgM Capture ELISA, to data generated using the original version of the kit. The same sample sets were used in this comparison, and reference test results for these samples were used to assess sensitivity, specificity, accuracy and concordance of results across two laboratories. Average sensitivity increased from 90.4% to 92.5% with the updated kit where the increase was not statistically different, and specificity increased from 79.5% to 97.4%, a statistically-significant difference. Accuracy of the ZIKV Detect™ 2.0 IgM Capture ELISA was 89% compared to 63.9% for the original version of the kit, and agreement across the laboratories increased from 79.5% to 97.4%. With secondary dengue virus infections, specificity increased from 9.3% to 82.6% with the updated kit, primarily due to the change in interpretation criteria that no longer includes "Possible Zika positive."

Evaluation of in vivo expressed Borrelia burgdorferi antigens for improved IgM serodiagnosis of early Lyme disease.

Improved serologic tests are needed for accurate diagnosis and proper treatment of early stage Lyme disease. We evaluated the 3 antigens currently used for 2-tiered IgM immunoblot testing (FlaB, OspC, and BmpA) in combination with 3 additional antigens (BBA65, BBA70, and BBA73) and measured the sensitivity and specificity against a serum repository of positive and negative controls. Using 3 statistical methods for positivity cutoff determinations and scoring criteria, we found increased sensitivities for early Lyme disease when 2 of 6 antigens were positive as compared with the 2 of 3 antigen IgM criteria currently used for second-tier immunoblot scoring. Specificities for negative controls were comparable or superior to using 2 of 3 antigens. These results indicate that IgM sensitivity and specificity of serological testing for Lyme disease in the early stages of illness can be improved by employing antigens that target the initial host antibody responses.

Distinguishing patients with laboratory-confirmed chikungunya from dengue and other acute febrile illnesses, Puerto Rico, 2012-2015.

Chikungunya, a mosquito-borne viral, acute febrile illness (AFI) is associated with polyarthralgia and polyarthritis. Differentiation from other AFI is difficult due to the non-specific presentation and limited availability of diagnostics. This 3-year study identified independent clinical predictors by day post-illness onset (DPO) at presentation and age-group that distinguish chikungunya cases from two groups: other AFI and dengue. Specimens collected from participants with fever ≤7 days were tested for chikungunya, dengue viruses 1-4, and 20 other pathogens. Of 8,996 participants, 18.2% had chikungunya, and 10.8% had dengue. Chikungunya cases were more likely than other groups to be older, report a chronic condition, and present <3 DPO. Regardless of timing of presentation, significant positive predictors for chikungunya versus other AFI were: joint pain, muscle, bone or back pain, skin rash, and red conjunctiva; with dengue as the comparator, red swollen joints (arthritis), joint pain, skin rash, any bleeding, and irritability were predictors. Chikungunya cases were less likely than AFI and dengue to present with thrombocytopenia, signs of poor circulation, diarrhea, headache, and cough. Among participants presenting <3 DPO, predictors for chikungunya versus other AFI included: joint pain, skin rash, and muscle, bone or back pain, and absence of thrombocytopenia, poor circulation and respiratory or gastrointestinal symptoms; when the comparator was dengue, joint pain and arthritis, and absence of thrombocytopenia, leukopenia, and nausea were early predictors. Among all groups presenting 3-5 DPO, pruritic skin became a predictor for chikungunya, joint, muscle, bone or back pain were no longer predictive, while arthritis became predictive in all age-groups. Absence of thrombocytopenia was a significant predictor regardless of DPO or comparison group. This study identified robust clinical indicators such as joint pain, skin rash and absence of thrombocytopenia that can allow early identification of and accurate differentiation between patients with chikungunya and other common causes of AFI.

Prevalence and Geographic Distribution of Borrelia miyamotoi in Host-Seeking Ixodes pacificus (Acari: Ixodidae) Nymphs in Mendocino County, California.

Borrelia miyamotoi is an increasingly recognized human pathogen transmitted by Ixodes ticks in the Northern Hemisphere. In North America, infection prevalences of B. miyamotoi are characteristically low (<10%) in Ixodes scapularis (Say; Acari: Ixodidae) and Ixodes pacificus (Cooley & Kohls; Acari: Ixodidae), both of which readily bite humans. We tested 3,255 host-seeking I. pacificus nymphs collected in 2004 from 79 sites throughout Mendocino County in north-coastal California for presence of B. miyamotoi. The collection sites represented a variety of forest types ranging from hot, dry oak woodlands in the southeast, to coastal redwoods in the west, and Ponderosa pine and Douglas fir-dominated areas in the northern part of the county. We found that B. miyamotoi was geographically widespread, but infected I. pacificus nymphs infrequently (cumulative prevalence of 1.4%). Infection prevalence was not significantly associated with geographic region or woodland type, and neither density of host-seeking nymphs, nor infection with Borrelia burgdorferi sensu stricto was associated with B. miyamotoi infection status in individual ticks. Because B. burgdorferi prevalence at the same sites was previously associated with woodland type and nymphal density, our results suggest that despite sharing a common vector, the primary modes of enzootic maintenance for the two pathogens are likely different.