Last data update: Oct 28, 2024. (Total: 48004 publications since 2009)
Records 1-30 (of 79 Records) |
Query Trace: Mead PS[original query] |
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Surveillance for lyme disease after implementation of a revised case definition - United States, 2022
Kugeler KJ , Earley A , Mead PS , Hinckley AF . MMWR Morb Mortal Wkly Rep 2024 73 (6) 118-123 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
Wu HJ , Bostic TD , Horiuchi K , Kugeler KJ , Mead PS , Nelson CA . Clin Infect Dis 2024 78 S29-s37 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
Apangu T , Candini G , Abaru J , Candia B , Okoth FJ , Atiku LA , Griffith KS , Hayden MH , Zielinski-Gutiérrez E , Schwartz AM , McCormick DW , Mead PS , Kugeler KJ . Am J Trop Med Hyg 2023 109 (5) 1129-1136 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. |
Human plague: An old scourge that needs new answers.
Vallès X , Stenseth NC , Demeure C , Horby P , Mead PS , Cabanillas O , Ratsitorahina M , Rajerison M , Andrianaivoarimanana V , Ramasindrazana B , Pizarro-Cerda J , Scholz HC , Girod R , Hinnebusch BJ , Vigan-Womas I , Fontanet A , Wagner DM , Telfer S , Yazdanpanah Y , Tortosa P , Carrara G , Deuve J , Belmain SR , D'Ortenzio E , Baril L . PLoS Negl Trop Dis 2020 14 (8) e0008251 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. |
Nomenclature for human infections caused by relapsing fever Borrelia
Mead PS . Emerg Infect Dis 2023 29 (5) 1084 Vazquez et al. report a convincing case of relapsing fever caused by Borrelia lonestari bacteria (1). This discovery highlights an existing problem with the nomenclature for relapsing fever. | | Tick-borne relapsing fever (TBRF) is the name given to illness caused by several genospecies of relapsing fever Borrelia bacteria, all of which are transmitted by argasid (soft) ticks (2). The limitations of this term became apparent after discovery of B. miyamotoi, a related genospecies that is transmitted by ixodid (hard) ticks and causes illness that differs epidemiologically from traditional TBRF (3). Consequently, 3 terms are used in the scientific literature to describe B. miyamotoi infections: Borrelia miyamotoi disease, hard tick–borne relapsing fever, and hard tick relapsing fever (3,4). In the interest of standard nomenclature, it is worth considering objectively the relative merits of each term. |
Prolonged shedding of Zika virus in human semen is associated with male reproductive tract inflammation.
Vogt MB , McDonald EM , Delorey M , Mead PS , Hook SA , Hinckley AF , Werre SR , Brault AC , Duggal NK . J Infect Dis 2022 226 (7) 1140-1150 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 are unknown. Previously, we found that ∼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 prolonged ZIKV RNA shedding in semen was associated with male reproductive tract inflammation, indicated by higher leukocyte counts and inflammatory cytokine concentrations in semen of long-term versus short-term shedders. Additionally, we found ZIKV RNA in seminal leukocytes and epithelial cells. This study of human semen from ZIKV-infected men provides critical insights into impacts of ZIKV on male reproductive tract health. |
Effectiveness of personal protection measures against Lyme disease: A review of epidemiologic studies from the United States
Schwartz AM , Mackeprang JM , Mead PS , Hinckley AF . Zoonoses Public Health 2022 69 (7) 777-791 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. |
Post-treatment Lyme borreliosis in context: Advancing the science and patient care
Marx GE , Hinckley AF , Mead PS . Lancet Reg Health Eur 2021 6 100153 The most common tickborne disease in both Europe and the United States, Lyme borreliosis (LB) can range from mild to severe forms of illness. If not recognized and treated during early localized disease, which typically presents as a large, slowly expanding erythema migrans rash, the Borrelia spirochete can disseminate, causing diverse pathologies including cranial neuritis, carditis, meningitis, and acute arthritis. Although most patients with LB recover completely when treated with antibiotics, some report persistent symptoms of fatigue, pain, or cognitive impairment lasting months or even years [1]. Because these symptoms are also ubiquitous in the general population, drawing a clear association between these lingering symptoms and treated LB has remained elusive. |
Antimicrobial Treatment and Prophylaxis of Plague: Recommendations for Naturally Acquired Infections and Bioterrorism Response
Nelson CA , Meaney-Delman D , Fleck-Derderian S , Cooley KM , Yu PA , Mead PS . MMWR Recomm Rep 2021 70 (3) 1-27 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. |
Changing Trends in Age and Sex Distributions of Lyme Disease-United States, 1992-2016
Kugeler KJ , Mead PS , Schwartz AM , Hinckley AF . Public Health Rep 2021 137 (4) 333549211026777 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. |
Prevention of Lyme and other tickborne diseases using a rodent-targeted approach: A randomized controlled trial in Connecticut
Hinckley AF , Niesobecki SA , Connally NP , Hook SA , Biggerstaff BJ , Horiuchi KA , Hojgaard A , Mead PS , Meek JI . Zoonoses Public Health 2021 68 (6) 578-587 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. |
Epidemiology, Ecology and Prevention of Plague in the West Nile Region of Uganda: The Value of Long-Term Field Studies
Eisen RJ , Atiku LA , Enscore RE , Mpanga JT , Acayo S , Mead PS , Apangu T , Yockey BM , Borchert JN , Beard CB , Gage KL . Am J Trop Med Hyg 2021 105 (1) 18-23 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. |
Estimating the frequency of Lyme disease diagnoses, United States, 2010-2018
Kugeler KJ , Schwartz AM , Delorey MJ , Mead PS , Hinckley AF . Emerg Infect Dis 2021 27 (2) 616-619 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. |
Treatment of human plague: A systematic review of published aggregate data on antimicrobial efficacy, 1939-2019
Godfred-Cato S , Cooley KM , Fleck-Derderian S , Becksted HA , Russell Z , Meaney-Delman D , Mead PS , Nelson CA . Clin Infect Dis 2020 70 S11-s19 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
Kugeler KJ , Mead PS , Campbell SB , Nelson CA . Clin Infect Dis 2020 70 S20-s26 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
Nelson CA , Fleck-Derderian S , Cooley KM , Meaney-Delman D , Becksted HA , Russell Z , Renaud B , Bertherat E , Mead PS . Clin Infect Dis 2020 70 S3-s10 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.
Moriarty LF , Plucinski MM , Marston BJ , Kurbatova EV , Knust B , Murray EL , Pesik N , Rose D , Fitter D , Kobayashi M , Toda M , Canty PT , Scheuer T , Halsey ES , Cohen NJ , Stockman L , Wadford DA , Medley AM , Green G , Regan JJ , Tardivel K , White S , Brown C , Morales C , Yen C , Wittry B , Freeland A , Naramore S , Novak RT , Daigle D , Weinberg M , Acosta A , Herzig C , Kapella BK , Jacobson KR , Lamba K , Ishizumi A , Sarisky J , Svendsen E , Blocher T , Wu C , Charles J , Wagner R , Stewart A , Mead PS , Kurylo E , Campbell S , Murray R , Weidle P , Cetron M , Friedman CR . MMWR Morb Mortal Wkly Rep 2020 69 (12) 347-352 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
Apangu T , Acayo S , Atiku LA , Apio H , Candini G , Okoth F , Basabose JK , Ojosia L , Ajoga S , Mongiba G , Wetaka MM , Kayiwa J , Balinandi S , Schwartz A , Yockey B , Sexton C , Dietrich EA , Pappert R , Petersen JM , Mead PS , Lutwama JJ , Kugeler KJ . MMWR Morb Mortal Wkly Rep 2020 69 (9) 241-244 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 tularensis infection in dogs: 88 cases (2014-2016)
Kwit NA , Middaugh NA , VinHatton ES , Melman SD , Onischuk L , Aragon AS , Nelson CA , Mead PS , Ettestad PJ . J Am Vet Med Assoc 2020 256 (2) 220-225 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. |
An evaluation of the flea index as a predictor of plague epizootics in the West Nile Region of Uganda
Eisen RJ , Atiku LA , Mpanga JT , Enscore RE , Acayo S , Kaggwa J , Yockey BM , Apangu T , Kugeler KJ , Mead PS . J Med Entomol 2019 57 (3) 893-900 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 opportunistica sp. nov., isolated from human blood and cerebrospinal fluid.
Dietrich EA , Kingry LC , Kugeler KJ , Levy C , Yaglom H , Young JW , Mead PS , Petersen JM . Int J Syst Evol Microbiol 2019 70 (2) 1145-1151 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, PA05-1188(T), available through the Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSM 107100) and the American Type Culture Collection (ATCC BAA-2974). |
Evaluating the potential misuse of the Lyme disease surveillance case definition
Perea AE , Hinckley AF , Mead PS . Public Health Rep 2019 135 (1) 33354919890024 Lyme disease has been a nationally notifiable condition in the United States since 1991. As with other diseases, surveillance for Lyme disease relies on an explicit case definition to promote comparability of data across locations and time.1 Although surveillance case definitions are based on key features of a disease, they are intended for the public health purposes of tracking trends and identifying populations at risk. They are not intended to be used by clinicians for making a clinical diagnosis or determining how to meet a patient’s health needs. Despite published disclaimers to this effect,2 commentaries suggest that clinicians frequently rely on the Lyme disease case definition to diagnose patients, leaving some patients with Lyme disease untreated.3,4 Congress also requested a report on how the Centers for Disease Control and Prevention is examining the potential misuse of the Lyme disease case definition.5 |
Human tularaemia associated with exposure to domestic dogs-United States, 2006-2016
Kwit NA , Schwartz A , Kugeler KJ , Mead PS , Nelson CA . Zoonoses Public Health 2018 66 (4) 417-421 Dogs have been implicated in the zoonotic transmission of numerous pathogens. Whereas cats are known to transmit Francisella tularensis to humans via bite and other routes, the role of dogs in facilitating infection is much less understood. We reviewed tularaemia case investigation records collected through national surveillance during 2006-2016 to summarize those with dog involvement, characterize the nature of dog-related exposure and describe associated clinical characteristics. Among 1,814 human tularaemia cases, 735 (41%) supplemental case investigation records were available for review; and of those, 24 (3.3%) were classified as dog-related. Median age of patients was 51 years (range: 1-82); 54% were female. Two thirds (67%) of cases presented with ulceroglandular/glandular tularaemia; pneumonic (13%) and oropharyngeal (13%) illness occurred less frequently. Dog-related exposures were classified as follows: direct contact via bite, scratch or face snuggling/licking (n = 12; 50%); direct contact with dead animals retrieved by domestic dogs (n = 8; 33%); and contact with infected ticks acquired from domestic dogs (n = 4; 17%). Prevention of dog-related tularaemia necessitates enhanced tularaemia awareness and tick avoidance among pet owners, veterinarians, health care providers and the general public. |
A cross-cutting approach to surveillance and laboratory capacity as a platform to improve health security in Uganda
Lamorde M , Mpimbaza A , Walwema R , Kamya M , Kapisi J , Kajumbula H , Sserwanga A , Namuganga JF , Kusemererwa A , Tasimwa H , Makumbi I , Kayiwa J , Lutwama J , Behumbiize P , Tagoola A , Nanteza JF , Aniku G , Workneh M , Manabe Y , Borchert JN , Brown V , Appiah GD , Mintz ED , Homsy J , Odongo GS , Ransom RL , Freeman MM , Stoddard RA , Galloway R , Mikoleit M , Kato C , Rosenberg R , Mossel EC , Mead PS , Kugeler KJ . Health Secur 2018 16 S76-s86 Global health security depends on effective surveillance for infectious diseases. In Uganda, resources are inadequate to support collection and reporting of data necessary for an effective and responsive surveillance system. We used a cross-cutting approach to improve surveillance and laboratory capacity in Uganda by leveraging an existing pediatric inpatient malaria sentinel surveillance system to collect data on expanded causes of illness, facilitate development of real-time surveillance, and provide data on antimicrobial resistance. Capacity for blood culture collection was established, along with options for serologic testing for select zoonotic conditions, including arboviral infection, brucellosis, and leptospirosis. Detailed demographic, clinical, and laboratory data for all admissions were captured through a web-based system accessible at participating hospitals, laboratories, and the Uganda Public Health Emergency Operations Center. Between July 2016 and December 2017, the expanded system was activated in pediatric wards of 6 regional government hospitals. During that time, patient data were collected from 30,500 pediatric admissions, half of whom were febrile but lacked evidence of malaria. More than 5,000 blood cultures were performed; 4% yielded bacterial pathogens, and another 4% yielded likely contaminants. Several WHO antimicrobial resistance priority pathogens were identified, some with multidrug-resistant phenotypes, including Acinetobacter spp., Citrobacter spp., Escherichia coli, Staphylococcus aureus, and typhoidal and nontyphoidal Salmonella spp. Leptospirosis and arboviral infections (alphaviruses and flaviviruses) were documented. The lessons learned and early results from the development of this multisectoral surveillance system provide the knowledge, infrastructure, and workforce capacity to serve as a foundation to enhance the capacity to detect, report, and rapidly respond to wide-ranging public health concerns in Uganda. |
Direct diagnostic tests for Lyme disease
Schutzer SE , Body BA , Boyle J , Branson BM , Dattwyler RJ , Fikrig E , Gerald NJ , Gomes-Solecki M , Kintrup M , Ledizet M , Levin AE , Lewinski M , Liotta LA , Marques A , Mead PS , Mongodin EF , Pillai S , Rao P , Robinson WH , Roth KM , Schriefer ME , Slezak T , Snyder JL , Steere AC , Witkowski J , Wong SJ , Branda JA . Clin Infect Dis 2018 68 (6) 1052-1057 Borrelia burgdorferi was discovered to be the cause of Lyme disease in 1983, leading to seroassays. The 1994 serodiagnostic testing guidelines predated a full understanding of key B. burgdorferi antigens and have a number of shortcomings. These serologic tests cannot distinguish active infection, past infection, or reinfection. Reliable direct-detection methods for active B. burgdorferi infection have been lacking in the past but are needed and appear achievable. New approaches have effectively been applied to other emerging infections and show promise in direct detection of B. burgdorferi infections. |
Vital Signs: Trends in reported vectorborne disease cases - United States and Territories, 2004-2016
Rosenberg R , Lindsey NP , Fischer M , Gregory CJ , Hinckley AF , Mead PS , Paz-Bailey G , Waterman SH , Drexler NA , Kersh GJ , Hooks H , Partridge SK , Visser SN , Beard CB , Petersen LR . MMWR Morb Mortal Wkly Rep 2018 67 (17) 496-501 INTRODUCTION: Vectorborne diseases are major causes of death and illness worldwide. In the United States, the most common vectorborne pathogens are transmitted by ticks or mosquitoes, including those causing Lyme disease; Rocky Mountain spotted fever; and West Nile, dengue, and Zika virus diseases. This report examines trends in occurrence of nationally reportable vectorborne diseases during 2004-2016. METHODS: Data reported to the National Notifiable Diseases Surveillance System for 16 notifiable vectorborne diseases during 2004-2016 were analyzed; findings were tabulated by disease, vector type, location, and year. RESULTS: A total 642,602 cases were reported. The number of annual reports of tickborne bacterial and protozoan diseases more than doubled during this period, from >22,000 in 2004 to >48,000 in 2016. Lyme disease accounted for 82% of all tickborne disease reports during 2004-2016. The occurrence of mosquitoborne diseases was marked by virus epidemics. Transmission in Puerto Rico, the U.S. Virgin Islands, and American Samoa accounted for most reports of dengue, chikungunya, and Zika virus diseases; West Nile virus was endemic, and periodically epidemic, in the continental United States. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Vectorborne diseases are a large and growing public health problem in the United States, characterized by geographic specificity and frequent pathogen emergence and introduction. Differences in distribution and transmission dynamics of tickborne and mosquitoborne diseases are often rooted in biologic differences of the vectors. To effectively reduce transmission and respond to outbreaks will require major national improvement of surveillance, diagnostics, reporting, and vector control, as well as new tools, including vaccines. |
Zika Virus Shedding in Semen of Symptomatic Infected Men.
Mead PS , Duggal NK , Hook SA , Delorey M , Fischer M , Olzenak McGuire D , Becksted H , Max RJ , Anishchenko M , Schwartz AM , Tzeng WP , Nelson CA , McDonald EM , Brooks JT , Brault AC , Hinckley AF . N Engl J Med 2018 378 (15) 1377-1385 BACKGROUND: Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that has been linked to adverse birth outcomes. Previous reports have shown that person-to-person transmission can occur by means of sexual contact. METHODS: We conducted a prospective study involving men with symptomatic ZIKV infection to determine the frequency and duration of ZIKV shedding in semen and urine and to identify risk factors for prolonged shedding in these fluids. Specimens were obtained twice per month for 6 months after illness onset and were tested by real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay for ZIKV RNA and by Vero cell culture and plaque assay for infectious ZIKV. RESULTS: A total of 1327 semen samples from 184 men and 1038 urine samples from 183 men were obtained 14 to 304 days after illness onset. ZIKV RNA was detected in the urine of 7 men (4%) and in the semen of 60 (33%), including in semen samples from 22 of 36 men (61%) who were tested within 30 days after illness onset. ZIKV RNA shedding in semen decreased substantially during the 3 months after illness onset but continued for 281 days in 1 man (1%). Factors that were independently associated with prolonged RNA shedding included older age, less frequent ejaculation, and the presence of certain symptoms at the time of initial illness. Infectious ZIKV was isolated from 3 of 78 semen samples with detectable ZIKV RNA, all obtained within 30 days after illness onset and all with at least 7.0 log10 ZIKV RNA copies per milliliter of semen. CONCLUSIONS: ZIKV RNA was commonly present in the semen of men with symptomatic ZIKV infection and persisted in some men for more than 6 months. In contrast, shedding of infectious ZIKV appeared to be much less common and was limited to the first few weeks after illness onset. (Funded by the Centers for Disease Control and Prevention.). |
Lyme disease testing in a high-incidence state: Clinician knowledge and patterns
Conant JL , Powers J , Sharp G , Mead PS , Nelson CA . Am J Clin Pathol 2018 149 (3) 234-240 Objectives: Lyme disease (LD) incidence is increasing, but data suggest some clinicians are not fully aware of recommended procedures for ordering and interpreting diagnostic tests. The study objective was to assess clinicians' knowledge and practices regarding LD testing in a high-incidence region. Methods: We distributed surveys to 1,142 clinicians in the University of Vermont Medical Center region, of which 144 were completed (12.6% response rate). We also examined LD laboratory test results and logs of calls to laboratory customer service over a period of 2.5 years and 6 months, respectively. Results: Most clinicians demonstrated basic knowledge of diagnostic protocols, but many misinterpreted Western blot results. For example, 42.4% incorrectly interpreted a positive immunoglobulin M result as an overall positive test in a patient with longstanding symptoms. Many also reported receiving patient requests for unvalidated tests. Conclusions: Additional education and modifications to LD test ordering and reporting systems would likely reduce errors and improve patient care. |
Risk factors for clinician-diagnosed Lyme arthritis, facial palsy, carditis, and meningitis in patients from high-incidence states
Kwit NA , Nelson CA , Max R , Mead PS . Open Forum Infect Dis 2018 5 (1) ofx254 Background: Clinical features of Lyme disease (LD) range from localized skin lesions to serious disseminated disease. Information on risk factors for Lyme arthritis, facial palsy, carditis, and meningitis is limited but could facilitate disease recognition and elucidate pathophysiology. Methods: Patients from high-incidence states treated for LD during 2005-2014 were identified in a nationwide insurance claims database using the International Classification of Diseases, Ninth Revision code for LD (088.81), antibiotic treatment history, and clinically compatible codiagnosis codes for LD manifestations. Results: Among 88022 unique patients diagnosed with LD, 5122 (5.8%) patients with 5333 codiagnoses were identified: 2440 (2.8%) arthritis, 1853 (2.1%) facial palsy, 534 (0.6%) carditis, and 506 (0.6%) meningitis. Patients with disseminated LD had lower median age (35 vs 42 years) and higher male proportion (61% vs 50%) than nondisseminated LD. Greatest differential risks included arthritis in males aged 10-14 years (odds ratio [OR], 3.5; 95% confidence interval [CI], 3.0-4.2), facial palsy (OR, 2.1; 95% CI, 1.6-2.7) and carditis (OR, 2.4; 95% CI, 1.6-3.6) in males aged 20-24 years, and meningitis in females aged 10-14 years (OR, 3.4; 95% CI, 2.1-5.5) compared to the 55-59 year referent age group. Males aged 15-29 years had the highest risk for complete heart block, a potentially fatal condition. Conclusions: The risk and manifestations of disseminated LD vary by age and sex. Provider education regarding at-risk populations and additional investigations into pathophysiology could enhance early case recognition and improve patient management. |
Plague in Madagascar - a tragic opportunity for improving public health
Mead PS . N Engl J Med 2017 378 (2) 106-108 When plague first arrived in Madagascar in November 1898, its appearance mirrored events in port cities around the world. Alexandria, Bombay, Buenos Aires, San Francisco, Saigon, and Sydney were all affected as part of the “third pandemic,” a global event that began in China but spread widely with the aid of long-distance steamships. Like the Justinian Plague of 542 c.e. and the Black Death of 1346 c.e., the third pandemic took millions of lives and disrupted societies. Although the disease eventually died out in some regions, enzootic foci established during the third pandemic persist in many areas, including the western United States and the central highlands of Madagascar. |
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