Lyme Disease Surveillance and Epidemiology in the United States: A Historical Perspective.

In the 40 years since Steere and colleagues first described Lyme disease, the illness has increased in incidence and distribution to become the most common vector-borne disease in the United States. Public health officials have developed, implemented, and revised surveillance systems to describe and monitor the condition. Much has been learned about the epidemiology of the illness, despite practical and logistical constraints that have encumbered the collection and interpretation of surveillance data. Future development of automated data collection from electronic health records as a source of surveillance and clinical information will address practical challenges and help answer ongoing questions about complications and persistent symptoms. Robust surveillance will be essential to monitor the effectiveness and safety of future vaccines and other preventive measures.

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.

Surveillance for Lyme Disease After Implementation of a Revised Case Definition - United States, 2022.

Lyme disease, a tickborne zoonosis caused by certain species of Borrelia spirochetes, is the most common vectorborne disease in the United States. Approximately 90% of all cases are reported from 15 high-incidence jurisdictions in the Northeast, mid-Atlantic, and upper-Midwest regions. After the implementation of a revised surveillance case definition in 2022, high-incidence jurisdictions report cases based on laboratory evidence alone, without need for additional clinical information. In 2022, 62,551 Lyme disease cases were reported to CDC, 1.7 times the annual average of 37,118 cases reported during 2017-2019. Annual incidence increased most in older age groups, with incidence among adults aged ≥65 years approximately double that during 2017-2019. The sharp increase in reported Lyme disease cases in 2022 likely reflects changes in surveillance methods rather than change in disease risk. Although these changes improve standardization of surveillance across jurisdictions, they preclude detailed comparison with historical data.

Characteristics of Hard Tick Relapsing Fever Caused by Borrelia miyamotoi, United States, 2013-2019.

Borrelia miyamotoi, transmitted by Ixodes spp. ticks, was recognized as an agent of hard tick relapsing fever in the United States in 2013. Nine state health departments in the Northeast and Midwest have conducted public health surveillance for this emerging condition by using a shared, working surveillance case definition. During 2013-2019, a total of 300 cases were identified through surveillance; 166 (55%) were classified as confirmed and 134 (45%) as possible. Median age of case-patients was 52 years (range 1-86 years); 52% were male. Most cases (70%) occurred during June-September, with a peak in August. Fever and headache were common symptoms; 28% of case-patients reported recurring fevers, 55% had arthralgia, and 16% had a rash. Thirteen percent of patients were hospitalized, and no deaths were reported. Ongoing surveillance will improve understanding of the incidence and clinical severity of this emerging disease.

Soft Tick Relapsing Fever - United States, 2012-2021.

Soft tick relapsing fever (STRF) (also known as tickborne relapsing fever) is a rare infection caused by certain Borrelia spirochetes and transmitted to humans by soft-bodied Ornithodoros ticks. In the United States, acquisition of STRF is commonly associated with exposure to rustic cabins, camping, and caves. Antibiotic treatment is highly effective for STRF, but without timely treatment, STRF can result in severe complications, including death. No nationally standardized case definition for STRF exists; however, the disease is reportable in 12 states. This report summarizes demographic and clinical information for STRF cases reported during 2012-2021 from states where STRF is reportable. During this period, 251 cases were identified in 11 states. The median annual case count was 24. Most patients with STRF (55%) were hospitalized; no fatalities were reported. The geographic distribution and seasonal pattern of STRF have remained relatively constant since the 1990s. Persons should avoid rodent-infested structures and rodent habitats, such as caves, in areas where STRF is endemic. STRF surveillance, prevention, and control efforts would benefit from a standardized case definition and increased awareness of the disease among the public and clinicians.

Characteristics of Reported Deaths Among Fully Vaccinated Persons With Coronavirus Disease 2019-United States, January-April 2021.

BACKGROUND: Vaccines against coronavirus disease 2019 (COVID-19) are highly efficacious, but severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections do occur after vaccination. We characterized COVID-19 cases among fully vaccinated persons with an outcome of death. METHODS: We analyzed COVID-19 cases voluntarily reported to the Centers for Disease Control and Prevention by US health departments from 1 January to 30 April 2021. We included cases among US residents with a positive SARS-CoV-2 test result ≥14 days after completion of an authorized primary vaccine series and who had a known outcome (alive or dead) as of 31 May 2021. When available, specimens were sequenced for viral lineage and death certificates were reviewed for cause(s) of death. RESULTS: Of 8084 fully vaccinated persons with reported COVID-19 during the surveillance period, 245 (3.0%) died. Compared with patients who remained alive, those who died were older (median age, 82 vs 57 years;), more likely to reside in a long-term care facility (51% vs 18%), and more likely to have ≥1 underlying health condition associated with risk for severe disease (64% vs 24%) (all P < .01). Among 245 deaths, 191 (78%) were classified as COVID-19 related. Of 106 deaths with available death certificates, COVID-19 was listed for 81 deaths (77%). There were no differences in the type of vaccine administered or the most common viral lineage (B.1.1.7). CONCLUSIONS: COVID-19 deaths are rare in fully vaccinated persons, occurring most commonly in those with risk factors for severe disease, including older age and underlying health conditions. All eligible persons should be fully vaccinated against COVID-19 and follow other prevention measures to mitigate exposure risk.

Incidence of Monkeypox Among Unvaccinated Persons Compared with Persons Receiving ≥1 JYNNEOS Vaccine Dose - 32 U.S. Jurisdictions, July 31-September 3, 2022.

Human monkeypox is caused by Monkeypox virus (MPXV), an Orthopoxvirus, previously rare in the United States (1). The first U.S. case of monkeypox during the current outbreak was identified on May 17, 2022 (2). As of September 28, 2022, a total of 25,341 monkeypox cases have been reported in the United States.* The outbreak has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) (3). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic), administered subcutaneously as a 2-dose (0.5 mL per dose) series with doses administered 4 weeks apart, was approved by the Food and Drug Administration (FDA) in 2019 to prevent smallpox and monkeypox infection (4). U.S. distribution of JYNNEOS vaccine as postexposure prophylaxis (PEP) for persons with known exposures to MPXV began in May 2022. A U.S. national vaccination strategy† for expanded PEP, announced on June 28, 2022, recommended subcutaneous vaccination of persons with known or presumed exposure to MPXV, broadening vaccination eligibility. FDA emergency use authorization (EUA) of intradermal administration of 0.1 mL of JYNNEOS on August 9, 2022, increased vaccine supply (5). As of September 28, 2022, most vaccine has been administered as PEP or expanded PEP. Because of the limited amount of time that has elapsed since administration of initial vaccine doses, as of September 28, 2022, relatively few persons in the current outbreak have completed the recommended 2-dose series.§ To examine the incidence of monkeypox among persons who were unvaccinated and those who had received ≥1 JYNNEOS vaccine dose, 5,402 reported monkeypox cases occurring among males¶ aged 18-49 years during July 31-September 3, 2022, were analyzed by vaccination status across 32 U.S. jurisdictions.** Average monkeypox incidence (cases per 100,000) among unvaccinated persons was 14.3 (95% CI = 5.0-41.0) times that among persons who received 1 dose of JYNNEOS vaccine ≥14 days earlier. Monitoring monkeypox incidence by vaccination status in timely surveillance data might provide early indications of vaccine-related protection that can be confirmed through other well-controlled vaccine effectiveness studies. This early finding suggests that a single dose of JYNNEOS vaccine provides some protection against monkeypox infection. The degree and durability of such protection is unknown, and it is recommended that people who are eligible for monkeypox vaccination receive the complete 2-dose series.

Evaluating risk factors associated with COVID-19 infections among vaccinated people early in the U.S. vaccination campaign: an observational study of five states, January-March 2021.

BACKGROUND: COVID-19 vaccines are an effective tool to prevent illness due to SARS-CoV-2 infection. However, infection after vaccination still occurs. We evaluated all infections identified among recipients of either the Pfizer-BioNTech or Moderna COVID-19 vaccine in five U.S. states during January-March 2021. METHODS: Using observational data reported to CDC, we compared the incidence of SARS-CoV-2 infection among vaccinated and unvaccinated persons, and the sex, age, and vaccine product received for individuals with vaccine breakthrough infections to those of the vaccinated population using Poisson regression models. We also compared the proportion of vaccine breakthrough cases due to a SARS-CoV-2 variant of concern to data reported to CDC's national genomic surveillance program. RESULTS: The age-adjusted incidence of reported SARS-CoV-2 infection was 97% lower among vaccinated as compared to unvaccinated persons aged ≥ 16 years (68 vs 2252 cases per 100,000 people). Vaccinated adults aged ≥ 85 years were 1.6 times (95% CI 1.3-1.9) as likely to become infected with SARS-CoV-2 than vaccinated adults aged < 65 years. Pfizer-BioNTech COVID-19 vaccine recipients were 1.4 times (95% CI 1.3-1.6) as likely to experience infection compared to Moderna COVID-19 recipients. The proportion of infections among vaccinated persons caused by SARS-CoV-2 variants of concern was similar to the proportion of circulating viruses identified as variants of concern in the five states during the same time. CONCLUSIONS: Vaccinated persons had a substantially lower incidence of SARS-CoV-2 infection compared to unvaccinated persons. Adults aged ≥ 85 years and Pfizer-BioNTech vaccine recipients had a higher risk of infection following vaccination. We provide an analytic framework for ongoing evaluation of patterns associated with SARS-CoV-2 infection among vaccinated persons using observational surveillance and immunization data. Our findings reinforce the effectiveness of COVID-19 vaccines in preventing infection in real-world settings.

Estimating the Frequency of Lyme Disease Diagnoses, United States, 2010-2018.

By using commercial insurance claims data, we estimated that Lyme disease was diagnosed and treated in ≈476,000 patients in the United States annually during 2010-2018. Our results underscore the need for accurate diagnosis and improved prevention.

Use of Commercial Claims Data for Evaluating Trends in Lyme Disease Diagnoses, United States, 2010-2018.

We evaluated MarketScan, a large commercial insurance claims database, for its potential use as a stable and consistent source of information on Lyme disease diagnoses in the United States. The age, sex, and geographic composition of the enrolled population during 2010-2018 remained proportionally stable, despite fluctuations in the number of enrollees. Annual incidence of Lyme disease diagnoses per 100,000 enrollees ranged from 49 to 88, ≈6-8 times higher than that observed for cases reported through notifiable disease surveillance. Age and sex distributions among Lyme disease diagnoses in MarketScan were similar to those of cases reported through surveillance, but proportionally more diagnoses occurred outside of peak summer months, among female enrollees, and outside high-incidence states. Misdiagnoses, particularly in low-incidence states, may account for some of the observed epidemiologic differences. Commercial claims provide a stable data source to monitor trends in Lyme disease diagnoses, but certain important characteristics warrant further investigation.

Effects of COVID-19 Pandemic on Reported Lyme Disease, United States, 2020.

Surveys indicate US residents spent more time outdoors in 2020 than in 2019, but fewer tick bite-related emergency department visits and Lyme disease laboratory tests were reported. Despite ongoing exposure, Lyme disease case reporting for 2020 might be artificially reduced due to coronavirus disease-associated changes in healthcare-seeking behavior.

Monitoring Incidence of COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Status - 13 U.S. Jurisdictions, April 4-July 17, 2021.

COVID-19 vaccine breakthrough infection surveillance helps monitor trends in disease incidence and severe outcomes in fully vaccinated persons, including the impact of the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19. Reported COVID-19 cases, hospitalizations, and deaths occurring among persons aged ≥18 years during April 4-July 17, 2021, were analyzed by vaccination status across 13 U.S. jurisdictions that routinely linked case surveillance and immunization registry data. Averaged weekly, age-standardized incidence rate ratios (IRRs) for cases among persons who were not fully vaccinated compared with those among fully vaccinated persons decreased from 11.1 (95% confidence interval [CI] = 7.8-15.8) to 4.6 (95% CI = 2.5-8.5) between two periods when prevalence of the Delta variant was lower (<50% of sequenced isolates; April 4-June 19) and higher (≥50%; June 20-July 17), and IRRs for hospitalizations and deaths decreased between the same two periods, from 13.3 (95% CI = 11.3-15.6) to 10.4 (95% CI = 8.1-13.3) and from 16.6 (95% CI = 13.5-20.4) to 11.3 (95% CI = 9.1-13.9). Findings were consistent with a potential decline in vaccine protection against confirmed SARS-CoV-2 infection and continued strong protection against COVID-19-associated hospitalization and death. Getting vaccinated protects against severe illness from COVID-19, including the Delta variant, and monitoring COVID-19 incidence by vaccination status might provide early signals of changes in vaccine-related protection that can be confirmed through well-controlled vaccine effectiveness (VE) studies.

Antimicrobial Treatment Patterns and Illness Outcome Among United States Patients With Plague, 1942-2018.

BACKGROUND: Plague is a rare and severe zoonotic illness with limited empiric evidence to support treatment recommendations. We summarize treatment information for all patients with plague in the United States (US) as collected under the auspices of public health surveillance. METHODS: We reviewed use of specific antimicrobials and illness outcome among cases of plague reported from 1942-2018. Antimicrobials were a priori classified into high-efficacy (aminoglycosides, tetracyclines, fluoroquinolones, sulfonamides, and chloramphenicol) and limited-efficacy classes (all others). Logistic regression models were created to describe associations between use of specific antimicrobial classes and illness outcome while controlling for potential confounding factors. RESULTS: Among 533 total reported plague cases during 1942-2018, 426 (80%) received high-efficacy antimicrobial therapy. Mortality differed significantly among those receiving high-efficacy therapy (9%) and only limited-efficacy therapy (51%). Aminoglycosides and tetracyclines were used more commonly than other classes, and their use was associated with increased odds of survival of plague. Gentamicin use was associated with higher mortality than streptomycin, and aminoglycoside use was linked to higher mortality than for tetracyclines. Fluoroquinolones have been used in treatment of >30% of patients in recent years and limited data suggest clinical effectiveness. CONCLUSIONS: Most US patients with plague have received effective antimicrobials. Aminoglycosides and tetracyclines substantially improve survival of plague, and fluoroquinolones may be equally as effective, yet lack sufficient data. Early recognition and early treatment with any of these antimicrobial classes remain the most important steps to improving survival of plague.

Targeted Metagenomics for Clinical Detection and Discovery of Bacterial Tick-Borne Pathogens.

Tick-borne diseases, due to a diversity of bacterial pathogens, represent a significant and increasing public health threat throughout the Northern Hemisphere. A high-throughput 16S V1-V2 rRNA gene-based metagenomics assay was developed and evaluated using >13,000 residual samples from patients suspected of having tick-borne illness and >1,000 controls. Taxonomic predictions for tick-borne bacteria were exceptionally accurate, as independently validated by secondary testing. Overall, 881 specimens were positive for bacterial tick-borne agents. Twelve tick-borne bacterial species were detected, including two novel pathogens, representing a 100% increase in the number of tick-borne bacteria identified compared to what was possible by initial PCR testing. In three blood specimens, two tick-borne bacteria were simultaneously detected. Seven bacteria, not known to be tick transmitted, were also confirmed to be unique to samples from persons suspected of having tick-borne illness. These results indicate that 16S V1-V2 metagenomics can greatly simplify diagnosis and accelerate the discovery of bacterial tick-borne pathogens.

Intervention To Stop Transmission of Imported Pneumonic Plague - Uganda, 2019.

Plague, an acute zoonosis caused by Yersinia pestis, is endemic in the West Nile region of northwestern Uganda and neighboring northeastern Democratic Republic of the Congo (DRC) (1-4). The illness manifests in multiple clinical forms, including bubonic and pneumonic plague. Pneumonic plague is rare, rapidly fatal, and transmissible from person to person via respiratory droplets. On March 4, 2019, a patient with suspected pneumonic plague was hospitalized in West Nile, Uganda, 4 days after caring for her sister, who had come to Uganda from DRC and died shortly thereafter, and 2 days after area officials received a message from a clinic in DRC warning of possible plague. The West Nile-based Uganda Virus Research Institute (UVRI) plague program, together with local health officials, commenced a multipronged response to suspected person-to-person transmission of pneumonic plague, including contact tracing, prophylaxis, and education. Plague was laboratory-confirmed, and no additional transmission occurred in Uganda. This event transpired in the context of heightened awareness of cross-border disease spread caused by ongoing Ebola virus disease transmission in DRC, approximately 400 km to the south. Building expertise in areas of plague endemicity can provide the rapid detection and effective response needed to mitigate epidemic spread and minimize mortality. Cross-border agreements can improve ability to respond effectively.

Francisella opportunistica sp. nov., isolated from human blood and cerebrospinal fluid.

Two isolates of a Gram-negative, non-spore-forming coccobacillus cultured from the blood and cerebrospinal fluid of immunocompromised patients in the United States were described previously. Biochemical and phylogenetic analyses revealed that they belong to a novel species within the Francisella genus. Here we describe a third isolate of this species, recovered from blood of a febrile patient with renal failure, and formally name the Francisella species. Whole genome comparisons indicated the three isolates display greater than 99.9 % average nucleotide identity (ANI) to each other and are most closely related to the tick endosymbiont F. persica, with only 88.6-88.8 % ANI to the type strain of F. persica. Based on biochemical, metabolic and genomic comparisons, we propose that these three isolates should be recognized as Francisella opportunistica sp. nov, with the type strain of the species, PA05-1188T, available through the Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSM 107100) and the American Type Culture Collection (ATCC BAA-2974).

Animal Exposure and Human Plague, United States, 1970-2017.

Since 1970, >50% of patients with plague in the United States had interactions with animals that might have led to infection. Among patients with pneumonic plague, nearly all had animal exposure. Improved understanding of the varied ways in which animal contact might increase risk for infection could enhance prevention messages.

Surveillance for and Discovery of Borrelia Species in US Patients Suspected of Tickborne Illness.

Background: Tick-transmitted Borrelia fall into 2 heterogeneous bacterial complexes comprised of multiple species, the relapsing fever (RF) group and the Borrelia burgdorferi sensu lato group, which are the causative agents of Lyme borreliosis (LB), the most common tickborne disease in the Northern Hemisphere. Geographic expansion of LB in the United States and discovery of emerging Borrelia pathogens underscores the importance of surveillance for disease-causing Borrelia. Methods: De-identified clinical specimens, submitted by providers throughout the United States, for patients suspected of LB, anaplasmosis, ehrlichiosis, or babesiosis were screened using a Borrelia genus-level TaqMan polymerase chain reaction (PCR). Borrelia species and sequence types (STs) were characterized by multilocus sequence typing (MLST) utilizing next-generation sequencing. Results: Among 7292 specimens tested, 5 Borrelia species were identified: 2 causing LB, B. burgdorferi (n = 25) and B. mayonii (n = 9), and 3 RF borreliae, B. hermsii (n = 1), B. miyamotoi (n = 8), and Candidatus B. johnsonii (n = 1), a species previously detected only in the bat tick, Carios kelleyi. ST diversity was greatest for B. burgdorferi-positive specimens, with new STs identified primarily among synovial fluids. Conclusions: These results demonstrate that broad PCR screening followed by MLST is a powerful surveillance tool for uncovering the spectrum of disease-causing Borrelia species, understanding their geographic distribution, and investigating the correlation between B. burgdorferi STs and joint involvement. Detection of Candidatus B. johnsonii in a patient with suspected tickborne disease suggests this species may be a previously undetected cause of illness in humans exposed to bat ticks.

Patterns of Human Plague in Uganda, 2008-2016.

Plague is a highly virulent fleaborne zoonosis that occurs throughout many parts of the world; most suspected human cases are reported from resource-poor settings in sub-Saharan Africa. During 2008-2016, a combination of active surveillance and laboratory testing in the plague-endemic West Nile region of Uganda yielded 255 suspected human plague cases; approximately one third were laboratory confirmed by bacterial culture or serology. Although the mortality rate was 7% among suspected cases, it was 26% among persons with laboratory-confirmed plague. Reports of an unusual number of dead rats in a patient's village around the time of illness onset was significantly associated with laboratory confirmation of plague. This descriptive summary of human plague in Uganda highlights the episodic nature of the disease, as well as the potential that, even in endemic areas, illnesses of other etiologies might be being mistaken for plague.

Lyme Disease in Hispanics, United States, 2000-2013.

Hispanics comprise a growing portion of the US population and might have distinct risk factors for tickborne diseases. During 2000-2013, a total of 5,473 Lyme disease cases were reported among Hispanics through national surveillance. Hispanics were more likely than non-Hispanics to have signs of disseminated infection and onset during fall months.