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.

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.

Engagement with Traditional Healers for Early Detection of Plague in Uganda.

In rural Uganda, many people who are ill consult traditional healers prior to visiting the formal healthcare system. Traditional healers provide supportive care for common illnesses, but their care may delay diagnosis and management of illnesses that can increase morbidity and mortality, hinder early detection of epidemic-prone diseases, and increase occupational risk to traditional healers. We conducted open-ended, semi-structured interviews with a convenience sample of 11 traditional healers in the plague-endemic West Nile region of northwestern Uganda to assess their knowledge, practices, and attitudes regarding plague and the local healthcare system. Most were generally knowledgeable about plague transmission and its clinical presentation and expressed willingness to refer patients to the formal healthcare system. We initiated a public health outreach program to further improve engagement between traditional healers and local health centers to foster trust in the formal healthcare system and improve early identification and referral of patients with plaguelike symptoms, which can reflect numerous other infectious and noninfectious conditions. During 2010-2019, 65 traditional healers were involved in the outreach program; 52 traditional healers referred 788 patients to area health centers. The diagnosis was available for 775 patients; malaria (37%) and respiratory tract infections (23%) were the most common diagnoses. One patient had confirmed bubonic plague. Outreach to improve communication and trust between traditional healers and local healthcare settings may result in improved early case detection and intervention not only for plague but also for other serious conditions.

Association Between Prolonged Shedding of Zika Virus in Human Semen and Male Reproductive Tract Inflammation.

Zika virus (ZIKV) is a mosquito-borne flavivirus that causes congenital defects. Sexual transmission of ZIKV was confirmed in a recent epidemic; however, mechanisms behind ZIKV infection and persistence in the male reproductive tract (MRT) are unknown. Previously, we found that approximately 33% of men with symptomatic ZIKV infections shed ZIKV RNA in semen, and some men shed ZIKV RNA for >3 months. Here, we evaluated the semen of 49 ZIKV-infected men to identify immune factors correlating with long-term ZIKV shedding in semen and ZIKV-infected cell types in semen. We found that prolonged ZIKV RNA shedding in semen was associated with MRT inflammation, indicated by higher leukocyte counts and inflammatory cytokine concentrations in semen of long-term versus short-term shedders. In addition, we found ZIKV RNA in seminal leukocytes and epithelial cells. This study of human semen from ZIKV-infected men provides critical insights into the effects of ZIKV on MRT health.

Effectiveness of personal protection measures against Lyme disease: A review of epidemiologic studies from the United States.

Lyme disease, the most commonly reported vector-borne disease in the United States, is caused by the bacteria Borrelia burgdorferi and is transmitted through the bite of an infected blacklegged tick. In the absence of a licensed vaccine, the prevention of Lyme disease relies heavily on limiting tick exposure. Methods for limiting tick exposure include personal protection measures such as repellent use, wearing protective clothing, avoiding areas where ticks may be present, bathing after exposure to tick habitat and performing regular tick checks. Public health officials typically recommend all these personal protection measures; however, there is limited evidence to promote one behaviour or practice over another. The focus of this article is to review available literature that examines the effectiveness of recommended personal protection measures to prevent Lyme and other Ixodes-transmitted diseases in humans. Articles included in this review were identified through Google Scholar and PubMed searches using specific search terms. We identified over 56,000 articles using Google Scholar and PubMed searches. Of those, 16 studies fit our criteria for inclusion and were reviewed in their entirety. Among the personal protection measures evaluated, no intervention was predominantly or consistently effective across studies, demonstrating that, currently, there is no single best method for primary prevention of Ixodes-transmitted diseases in the United States. Frequently recommended practices such as tick checks, repellent use and protective clothing had mixed results across studies. Study design differences limited comparability among studies, and sample sizes for these studies may have been too small to detect statistically significant results even if a prevention method was effective. Though many of the reviewed personal protection measures are frequently recommended to the public, limited evidence demonstrates their ability to prevent tick-borne disease. Additional standardized studies are needed to evaluate personal protection measures.

Changing Trends in Age and Sex Distributions of Lyme Disease-United States, 1992-2016.

Lyme disease is the most common vector-borne disease in the United States and is characterized by a bimodal age distribution and male predominance. We examined trends in reported cases during a 25-year period to describe changes in the populations most affected by Lyme disease in the United States. We examined demographic characteristics of people with confirmed cases of Lyme disease reported to the Centers for Disease Control and Prevention during 1992-2016 through the National Notifiable Diseases Surveillance System. We grouped cases into 5-year periods (1992-1996, 1997-2001, 2002-2006, 2007-2011, 2012-2016). We calculated the average annual incidence by age and sex and used incidence rate ratios (IRRs) to describe changes in Lyme disease incidence by age and sex over time. We converted patient age at time of illness into patient birth year to ascertain disease patterns according to birth cohorts. The incidence of Lyme disease in the United States doubled from 1992-1996 to 2012-2016 (IRR = 1.74; 95% CI, 1.70-1.78) and increased disproportionately among males; IRRs were 39%-89% higher among males than among females for most age groups. During the study period, children aged 5-9 years were most frequently and consistently affected. In contrast, the average age of adults with Lyme disease increased over time; of all adults, people born during 1950-1964 were the most affected by Lyme disease. Our findings suggest that age-related behaviors and susceptibilities may drive infections among children, and the shifting peak among adults likely reflects a probability proportional to the relative size of the baby boom population. These findings can inform targeted and efficient public health education and intervention efforts.

Antimicrobial Treatment and Prophylaxis of Plague: Recommendations for Naturally Acquired Infections and Bioterrorism Response.

This report provides CDC recommendations to U.S. health care providers regarding treatment, pre-exposure prophylaxis, and postexposure prophylaxis of plague. Yersinia pestis, the bacterium that causes plague, leads to naturally occurring disease in the United States and other regions worldwide and is recognized as a potential bioterrorism weapon. A bioweapon attack with Y. pestis could potentially infect thousands, requiring rapid and informed decision making by clinicians and public health agencies. The U.S. government stockpiles a variety of medical countermeasures to mitigate the effects of a bioterrorism attack (e.g., antimicrobials, antitoxins, and vaccines) for which the 21st Century Cures Act mandates the development of evidence-based guidelines on appropriate use. Guidelines for treatment and postexposure prophylaxis of plague were published in 2000 by a nongovernmental work group; since then, new human clinical data, animal study data, and U.S. Food and Drug Administration approvals of additional countermeasures have become available. To develop a comprehensive set of updated guidelines, CDC conducted a series of systematic literature reviews on human treatment of plague and other relevant topics to collect a broad evidence base for the recommendations in this report. Evidence from CDC reviews and additional sources were presented to subject matter experts during a series of forums. CDC considered individual expert input while developing these guidelines, which provide recommended best practices for treatment and prophylaxis of human plague for both naturally occurring disease and following a bioterrorism attack. The guidelines do not include information on diagnostic testing, triage decisions, or logistics involved in dispensing medical countermeasures. Clinicians and public health officials can use these guidelines to prepare their organizations, hospitals, and communities to respond to a plague mass-casualty event and as a guide for treating patients affected by plague.

Epidemiology, Ecology and Prevention of Plague in the West Nile Region of Uganda: The Value of Long-Term Field Studies.

Plague, a fleaborne rodent-associated zoonosis, is a neglected disease with most recent cases reported from east and central Africa and Madagascar. Because of its low incidence and sporadic occurrence, most of our knowledge of plague ecology, prevention, and control derives from investigations conducted in response to human cases. Long-term studies (which are uncommon) are required to generate data to support plague surveillance, prevention, and control recommendations. Here we describe a 15-year, multidisciplinary commitment to plague in the West Nile region of Uganda that led to significant advances in our understanding of where and when persons are at risk for plague infection and how to reduce morbidity and mortality. These findings provide data-driven support for several existing recommendations on plague surveillance and prevention and may be generalizable to other plague foci.

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.

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.

Human plague: An old scourge that needs new answers.

Yersinia pestis, the bacterial causative agent of plague, remains an important threat to human health. Plague is a rodent-borne disease that has historically shown an outstanding ability to colonize and persist across different species, habitats, and environments while provoking sporadic cases, outbreaks, and deadly global epidemics among humans. Between September and November 2017, an outbreak of urban pneumonic plague was declared in Madagascar, which refocused the attention of the scientific community on this ancient human scourge. Given recent trends and plague's resilience to control in the wild, its high fatality rate in humans without early treatment, and its capacity to disrupt social and healthcare systems, human plague should be considered as a neglected threat. A workshop was held in Paris in July 2018 to review current knowledge about plague and to identify the scientific research priorities to eradicate plague as a human threat. It was concluded that an urgent commitment is needed to develop and fund a strong research agenda aiming to fill the current knowledge gaps structured around 4 main axes: (i) an improved understanding of the ecological interactions among the reservoir, vector, pathogen, and environment; (ii) human and societal responses; (iii) improved diagnostic tools and case management; and (iv) vaccine development. These axes should be cross-cutting, translational, and focused on delivering context-specific strategies. Results of this research should feed a global control and prevention strategy within a "One Health" approach.

Treatment of Human Plague: A Systematic Review of Published Aggregate Data on Antimicrobial Efficacy, 1939-2019.

BACKGROUND: Plague, caused by the bacterium Yersinia pestis, has killed millions in historic pandemics and continues to cause sporadic outbreaks. Numerous antimicrobials are considered effective for treating plague; however, well-defined information on the relative efficacy of various treatments is lacking. We conducted a systematic review of published data on antimicrobial treatment of plague reported in aggregate. METHODS: We searched databases including Embase, Medline, CINAHL, Cochrane Library, and others for publications with terms related to plague and antimicrobials. Articles were included if they contained 1) a group of patients treated for plague, with outcomes reported by antimicrobial regimen, and 2) laboratory evidence of Y. pestis infection or an epidemiologic link to patients with laboratory evidence of Y. pestis. Case fatality rate by antimicrobial regimen was calculated. RESULTS: In total, 5837 articles were identified; among these, 26 articles published between 1939 and 2008 met inclusion criteria. A total of 2631 cases of human plague reported within these articles were included. Among cases classified by primary clinical form of plague, 93.6% were bubonic, 5.9% pneumonic, and 0.5% septicemic with associated case fatalities of 14.2%, 31.1%, and 20.0%, respectively. Case fatality rate among patients who received monotherapy with tetracyclines, chloramphenicol, aminoglycosides, or sulfonamides was 1.3%, 1.4%, 7.5%, and 20.2%, respectively. Fluoroquinolones were only given as part of combination therapy. Penicillin was associated with a case fatality rate of 75%. CONCLUSIONS: Tetracyclines, chloramphenicol, and aminoglycosides were associated with the lowest case fatality rates of all antimicrobials used for treatment of plague. Additional research is needed to determine the efficacy of fluoroquinolones as monotherapy.

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.

Antimicrobial Treatment of Human Plague: A Systematic Review of the Literature on Individual Cases, 1937-2019.

BACKGROUND: Yersinia pestis remains endemic in Africa, Asia, and the Americas and is a known bioterrorism agent. Treatment with aminoglycosides such as streptomycin or gentamicin is effective when initiated early in illness but can have serious side effects. Alternatives such as fluoroquinolones, tetracyclines, and sulfonamides are potentially safer but lack robust human data on efficacy. METHODS: We searched PubMed Central, Medline, Embase, and other databases for articles in any language with terms related to plague and antimicrobials. Articles that contained case-level information on antimicrobial treatment and patient outcome were included. We abstracted information related to patient demographics, clinical features, treatment, and fatality. RESULTS: Among 5837 articles screened, we found 762 published cases of treated plague reported from 1937 to 2019. Fifty-nine percent were male; median age was 22 years (range, 8 days-80 years). The case fatality rate was 20% overall. Most patients had primary bubonic (63%), pneumonic (21%), or septicemic (5%) plague, with associated case fatality rates of 17%, 27%, and 38%, respectively. Among those treated with an aminoglycoside (n = 407 [53%]), the case fatality rate was 13%. Among those treated with a sulfonamide (n = 322 [42%]), tetracycline (n = 171 [22%]), or fluoroquinolone (n = 61 [8%]), fatality was 23%, 10%, and 12%, respectively. Case fatality rate did not substantially differ between patients treated with 1 vs 2 classes of antimicrobials considered to be effective for plague. CONCLUSIONS: In addition to aminoglycosides, other classes of antimicrobials including tetracyclines, fluoroquinolones, and sulfonamides are effective for plague treatment, although publication bias and low numbers in certain treatment groups may limit interpretation.

Public Health Responses to COVID-19 Outbreaks on Cruise Ships - Worldwide, February-March 2020.

An estimated 30 million passengers are transported on 272 cruise ships worldwide each year* (1). Cruise ships bring diverse populations into proximity for many days, facilitating transmission of respiratory illness (2). SARS-CoV-2, the virus that causes coronavirus disease (COVID-19) was first identified in Wuhan, China, in December 2019 and has since spread worldwide to at least 187 countries and territories. Widespread COVID-19 transmission on cruise ships has been reported as well (3). Passengers on certain cruise ship voyages might be aged ≥65 years, which places them at greater risk for severe consequences of SARS-CoV-2 infection (4). During February-March 2020, COVID-19 outbreaks associated with three cruise ship voyages have caused more than 800 laboratory-confirmed cases among passengers and crew, including 10 deaths. Transmission occurred across multiple voyages of several ships. This report describes public health responses to COVID-19 outbreaks on these ships. COVID-19 on cruise ships poses a risk for rapid spread of disease, causing outbreaks in a vulnerable population, and aggressive efforts are required to contain spread. All persons should defer all cruise travel worldwide during the COVID-19 pandemic.

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.

An Evaluation of the Flea Index as a Predictor of Plague Epizootics in the West Nile Region of Uganda.

Plague is a low incidence flea-borne zoonosis that is often fatal if treatment is delayed or inadequate. Outbreaks occur sporadically and human cases are often preceded by epizootics among rodents. Early recognition of epizootics coupled with appropriate prevention measures should reduce plague morbidity and mortality. For nearly a century, the flea index (a measure of fleas per host) has been used as a measure of risk for epizootic spread and human plague case occurrence, yet the practicality and effectiveness of its use in surveillance programs has not been evaluated rigorously. We sought to determine whether long-term monitoring of the Xenopsylla flea index on hut-dwelling rats in sentinel villages in the plague-endemic West Nile region of Uganda accurately predicted plague occurrence in the surrounding parish. Based on observations spanning ~6 yr, we showed that on average, the Xenopsylla flea index increased prior to the start of the annual plague season and tended to be higher in years when plague activity was reported in humans or rodents compared with years when it was not. However, this labor-intensive effort had limited spatial coverage and was a poor predictor of plague activity within sentinel parishes.

Francisella tularensis infection in dogs: 88 cases (2014-2016).

OBJECTIVE: To characterize the epidemiology, clinical signs, and treatment of dogs with Francisella tularensis infection in New Mexico. ANIMALS: 87 dogs in which 88 cases of tularemia (1 dog had 2 distinct cases) were confirmed by the New Mexico Department of Health Scientific Laboratory Division from 2014 through 2016 and for which medical records were available. PROCEDURES: Dogs were confirmed to have tularemia if they had a 4-fold or greater increase in anti-F tularensis antibody titer between acute and convalescent serum samples or F tularensis had been isolated from a clinical or necropsy specimen. Epidemiological, clinical, and treatment information were collected from the dogs' medical records and summarized. RESULTS: All 88 cases of tularemia were confirmed by paired serologic titers; the first (acute) serologic test result was negative for 84 (95%) cases. The most common reported exposure to F tularensis was wild rodent or rabbit contact (53/88 [60%]). Dogs had a median number of 3 clinical signs at initial evaluation; lethargy (81/88 [92%]), pyrexia (80/88 [91%]), anorexia (67/88 [76%]), and lymphadenopathy (18/88 [20%]) were most common. For 32 (36%) cases, the dog was hospitalized; all hospitalized dogs survived. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with F tularensis infection often had nonspecific clinical signs and developed moderate to severe illness, sometimes requiring hospitalization. Veterinarians examining dogs from tularemia-enzootic areas should be aware of the epidemiology and clinical signs of tularemia, inquire about potential exposures, and discuss prevention methods with owners, including reducing exposure to reservoir hosts and promptly seeking care for ill animals.