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Paul Mead - Top 30 Publications

Knowledge and practices related to plague in an endemic area of Uganda.

Plague is a virulent zoonosis reported most commonly from sub-Saharan Africa. Early treatment with antibiotics is important to prevent mortality. Understanding knowledge gaps and common behaviors informs development of educational efforts to reduce plague mortality.

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.

Correction: Lyme borreliosis.

This corrects the article DOI: 10.1038/nrdp.2016.90.

Serious Bacterial Infections Acquired During Treatment of Patients Given a Diagnosis of Chronic Lyme Disease - United States.

The term "chronic Lyme disease" is used by some health care providers as a diagnosis for various constitutional, musculoskeletal, and neuropsychiatric symptoms (1,2). Patients with a diagnosis of chronic Lyme disease have been provided a wide range of medications as treatment, including long courses of intravenous (IV) antibiotics (3,4). Studies have not shown that such treatments lead to substantial long-term improvement for patients, and they can be harmful (1,5). This report describes cases of septic shock, osteomyelitis, Clostridium difficile colitis, and paraspinal abscess resulting from treatments for chronic Lyme disease. Patients, clinicians, and public health practitioners should be aware that treatments for chronic Lyme disease can carry serious risks.

Unique Case of Disseminated Plague With Multifocal Osteomyelitis.

Plague is a disease caused by Yersinia pestis. Septicemic and pneumonic plague have a high mortality rate if untreated. Here we describe the challenges of accurately diagnosing a nonfatal pediatric case of septicemic plague with involvement of multiple organs; to our knowledge, the first documented case of multifocal plague osteomyelitis.

Successful Treatment of Human Plague with Oral Ciprofloxacin.

The US Food and Drug Administration recently approved ciprofloxacin for treatment of plague (Yersina pestis infection) based on animal studies. Published evidence of efficacy in humans is sparse. We report 5 cases of culture-confirmed human plague treated successfully with oral ciprofloxacin, including 1 case of pneumonic plague.

Zika Virus -10 Public Health Achievements in 2016 and Future Priorities.

The introduction of Zika virus into the Region of the Americas (Americas) and the subsequent increase in cases of congenital microcephaly resulted in activation of CDC's Emergency Operations Center on January 22, 2016, to ensure a coordinated response and timely dissemination of information, and led the World Health Organization to declare a Public Health Emergency of International Concern on February 1, 2016. During the past year, public health agencies and researchers worldwide have collaborated to protect pregnant women, inform clinicians and the public, and advance knowledge about Zika virus (Figure 1). This report summarizes 10 important contributions toward addressing the threat posed by Zika virus in 2016. To protect pregnant women and their fetuses and infants from the effects of Zika virus infection during pregnancy, public health activities must focus on preventing mosquito-borne transmission through vector control and personal protective practices, preventing sexual transmission by advising abstention from sex or consistent and correct use of condoms, and preventing unintended pregnancies by reducing barriers to access to highly effective reversible contraception.

Male-to-Female Sexual Transmission of Zika Virus-United States, January-April 2016.

We report on 9 cases of male-to-female sexual transmission of Zika virus in the United States occurring January-April 2016. This report summarizes new information about both timing of exposure and symptoms of sexually transmitted Zika virus disease, and results of semen testing for Zika virus from 2 male travelers.

Lyme borreliosis.

Lyme borreliosis is a tick-borne disease that predominantly occurs in temperate regions of the northern hemisphere and is primarily caused by the bacterium Borrelia burgdorferi in North America and Borrelia afzelii or Borrelia garinii in Europe and Asia. Infection usually begins with an expanding skin lesion, known as erythema migrans (referred to as stage 1), which, if untreated, can be followed by early disseminated infection, particularly neurological abnormalities (stage 2), and by late infection, especially arthritis in North America or acrodermatitis chronica atrophicans in Europe (stage 3). However, the disease can present with any of these manifestations. During infection, the bacteria migrate through the host tissues, adhere to certain cells and can evade immune clearance. Yet, these organisms are eventually killed by both innate and adaptive immune responses and most inflammatory manifestations of the infection resolve. Except for patients with erythema migrans, Lyme borreliosis is diagnosed based on a characteristic clinical constellation of signs and symptoms with serological confirmation of infection. All manifestations of the infection can usually be treated with appropriate antibiotic regimens, but the disease can be followed by post-infectious sequelae in some patients. Prevention of Lyme borreliosis primarily involves the avoidance of tick bites by personal protective measures.

Investigation of and Response to 2 Plague Cases, Yosemite National Park, California, USA, 2015.

In August 2015, plague was diagnosed for 2 persons who had visited Yosemite National Park in California, USA. One case was septicemic and the other bubonic. Subsequent environmental investigation identified probable locations of exposure for each patient and evidence of epizootic plague in other areas of the park. Transmission of Yersinia pestis was detected by testing rodent serum, fleas, and rodent carcasses. The environmental investigation and whole-genome multilocus sequence typing of Y. pestis isolates from the patients and environmental samples indicated that the patients had been exposed in different locations and that at least 2 distinct strains of Y. pestis were circulating among vector-host populations in the area. Public education efforts and insecticide applications in select areas to control rodent fleas probably reduced the risk for plague transmission to park visitors and staff.

Cat-Scratch Disease in the United States, 2005-2013.

Cat-scratch disease (CSD) is mostly preventable. More information about the epidemiology and extent of CSD would help direct prevention efforts to those at highest risk. To gain such information, we reviewed the 2005-2013 MarketScan national health insurance claims databases and identified patients <65 years of age with an inpatient admission or outpatient visit that included a CSD code from the International Classification of Diseases, Ninth Revision, Clinical Modification. Incidence of CSD was highest among those who lived in the southern United States (6.4 cases/100,000 population) and among children 5-9 years of age (9.4 cases/100,000 population). Inpatients were significantly more likely than outpatients to be male and 50-64 years of age. We estimate that each year, 12,000 outpatients are given a CSD diagnosis and 500 inpatients are hospitalized for CSD. Prevention measures (e.g., flea control for cats) are particularly helpful in southern states and in households with children.

Borrelia mayonii sp. nov., a member of the Borrelia burgdorferi sensu lato complex, detected in patients and ticks in the upper midwestern United States.

Lyme borreliosis (LB) is a multisystem disease caused by spirochetes in the Borrelia burgdorferisensu lato (Bbsl) genospecies complex. We previously described a novel Bbsl genospecies (type strain MN14-1420T) that causes LB among patients with exposures to ticks in the upper midwestern USA. Patients infected with the novel Bbsl genospecies demonstrated higher levels of spirochetemia and somewhat differing clinical symptoms as compared with those infected with other Bbsl genospecies. The organism was detected from human specimens using PCR, microscopy, serology and culture. The taxonomic status was determined using an eight-housekeeping-gene (uvrA, rplB, recG, pyrG, pepX, clpX, clpA and nifS) multi-locus sequence analysis (MLSA) and comparison of 16S rRNA gene, flaB, rrf-rrl, ospC and oppA2 nucleotide sequences. Using a system threshold of 98.3 % similarity for delineation of Bbsl genospecies by MLSA, we demonstrated that the novel species is a member of the Bbsl genospecies complex, most closely related to B. burgdorferisensu stricto (94.7-94.9 % similarity). This same species was identified in Ixodes scapularis ticks collected in Minnesota and Wisconsin. This novel species, Borrelia mayonii sp. nov, is formally described here. The type strain, MN14-1420, is available through the Deutsche Sammlung von Mikroorganismen und Zelkulturen GmbH (DSM 102811) and the American Type Culture Collection (ATCC BAA-2743).

Current Guidelines, Common Clinical Pitfalls, and Future Directions for Laboratory Diagnosis of Lyme Disease, United States.

In the United States, Lyme disease is caused by Borrelia burgdorferi and transmitted to humans by blacklegged ticks. Patients with an erythema migrans lesion and epidemiologic risk can receive a diagnosis without laboratory testing. For all other patients, laboratory testing is necessary to confirm the diagnosis, but proper interpretation depends on symptoms and timing of illness. The recommended laboratory test in the United States is 2-tiered serologic analysis consisting of an enzyme-linked immunoassay or immunofluorescence assay, followed by reflexive immunoblotting. Sensitivity of 2-tiered testing is low (30%-40%) during early infection while the antibody response is developing (window period). For disseminated Lyme disease, sensitivity is 70%-100%. Specificity is high (>95%) during all stages of disease. Use of other diagnostic tests for Lyme disease is limited. We review the rationale behind current US testing guidelines, appropriate use and interpretation of tests, and recent developments in Lyme disease diagnostics.

Case Report: Cervical chondrocalcinosis as a complication of Gitelman syndrome.

Gitelman syndrome is an inherited tubulopathy leading to a hypokalaemic metabolic alkalosis with hypomagnesaemia and hypocalciuria. Most cases are due to mutations in SLC12A3, encoding the apical thiazide sensitive co-transporter in the distal convoluted tubule. Musculoskeletal effects of Gitelman syndrome are common, including muscle weakness, tetany and cramps. Chronic hypomagnesaemia can lead to chondrocalcinosis, which often affects knees but can affect other joints. Here we present a case of Gitelman syndrome complicated by cervical chondrocalcinosis leading to neck pain and numbness of the fingers. Treatments directed at correcting both hypokalaemia and hypomagnesaemia were initiated and allowed conservative non-surgical management of the neck pain. Recognition of chondrocalcinosis is important and treatments must be individualised to correct the underlying hypomagnesaemia.

The heat is on: Killing blacklegged ticks in residential washers and dryers to prevent tickborne diseases.

Reducing exposure to ticks can help prevent Lyme disease and other tickborne diseases. Although it is currently recommended to dry clothes on high heat for one hour to kill ticks on clothing after spending time outdoors, this recommendation is based on a single published study of tick survival under various washing conditions and a predetermined one-hour drying time. We conducted a series of tests to investigate the effects of temperature, humidity, and drying time on killing nymphal and adult blacklegged ticks (Ixodes scapularis). Muslin bags containing 5 ticks each were washed then dried or dried only with six cotton towels during each drying cycle. All nymphal and adult ticks were killed when exposed to wash cycles when the water temperature reached ≥54°C (≥130°F); however, 50% of ticks survived hot water washes when the water temperature was <54°C. The majority (94%) of ticks survived warm washes [temperature range, 27-46°C (80-115°F)] and all ticks survived cold washes [15-27°C (59-80°F)]. When subsequently dried on high heat setting [54-85°C (129-185°F)], it took 50min to kill all ticks (95% confidence limit, 55min). Most significantly, we found that all adult and nymphal ticks died when placed directly in the dryer with dry towels and dried for 4min on high heat (95% confidence limit, 6min). We have identified effective, easily implemented methods to rid clothing of ticks after spending time outdoors. Placing clothing directly in a dryer and drying for a minimum of 6min on high heat will effectively kill ticks on clothing. If clothing is soiled and requires washing first, our results indicate clothing should be washed with water temperature ≥54°C (≥130°F) to kill ticks. When practiced with other tick-bite prevention methods, these techniques could further reduce the risk of acquiring tickborne diseases.

Lack of Evidence for Plague or Anthrax on the New York City Subway.

Ackelsberg et al. point out a lack of evidence in the dataset of Afshinekoo et al. for the presence of plague and anthrax on the New York City subway.

Male-to-Male Sexual Transmission of Zika Virus--Texas, January 2016.

Zika virus infection has been linked to increased risk for Guillain-Barré syndrome and adverse fetal outcomes, including congenital microcephaly. In January 2016, after notification from a local health care provider, an investigation by Dallas County Health and Human Services (DCHHS) identified a case of sexual transmission of Zika virus between a man with recent travel to an area of active Zika virus transmission (patient A) and his nontraveling male partner (patient B). At this time, there had been one prior case report of sexual transmission of Zika virus. The present case report indicates Zika virus can be transmitted through anal sex, as well as vaginal sex. Identification and investigation of cases of sexual transmission of Zika virus in nonendemic areas present valuable opportunities to inform recommendations to prevent sexual transmission of Zika virus.

Zika Virus Disease: A CDC Update for Pediatric Health Care Providers.

Zika virus is a mosquito-borne flavivirus discovered in Africa in 1947. Most persons with Zika virus infection are asymptomatic; symptoms when present are generally mild and include fever, maculopapular rash, arthralgia, and conjunctivitis. Since early 2015, Zika virus has spread rapidly through the Americas, with local transmission identified in 31 countries and territories as of February 29, 2016, including several US territories. All age groups are susceptible to Zika virus infection, including children. Maternal-fetal transmission of Zika virus has been documented; evidence suggests that congenital Zika virus infection is associated with microcephaly and other adverse pregnancy and infant outcomes. Perinatal transmission has been reported in 2 cases; 1 was asymptomatic, and the other had thrombocytopenia and a rash. Based on limited information, Zika virus infection in children is mild, similar to that in adults. The long-term sequelae of congenital, perinatal, and pediatric Zika virus infection are largely unknown. No vaccine to prevent Zika virus infection is available, and treatment is supportive. The primary means of preventing Zika virus infection is prevention of mosquito bites in areas with local Zika virus transmission. Given the possibility of limited local transmission of Zika virus in the continental United States and frequent travel from affected countries to the United States, US pediatric health care providers need to be familiar with Zika virus infection. This article reviews the Zika virus, its epidemiologic characteristics, clinical presentation, laboratory testing, treatment, and prevention to assist providers in the evaluation and management of children with possible Zika virus infection.

Cardiac Tropism of Borrelia burgdorferi: An Autopsy Study of Sudden Cardiac Death Associated with Lyme Carditis.

Fatal Lyme carditis caused by the spirochete Borrelia burgdorferi rarely is identified. Here, we describe the pathologic, immunohistochemical, and molecular findings of five case patients. These sudden cardiac deaths associated with Lyme carditis occurred from late summer to fall, ages ranged from young adult to late 40s, and four patients were men. Autopsy tissue samples were evaluated by light microscopy, Warthin-Starry stain, immunohistochemistry, and PCR for B. burgdorferi, and immunohistochemistry for complement components C4d and C9, CD3, CD79a, and decorin. Post-mortem blood was tested by serology. Interstitial lymphocytic pancarditis in a relatively characteristic road map distribution was present in all cases. Cardiomyocyte necrosis was minimal, T cells outnumbered B cells, plasma cells were prominent, and mild fibrosis was present. Spirochetes in the cardiac interstitium associated with collagen fibers and co-localized with decorin. Rare spirochetes were seen in the leptomeninges of two cases by immunohistochemistry. Spirochetes were not seen in other organs examined, and joint tissue was not available for evaluation. Although rare, sudden cardiac death caused by Lyme disease might be an under-recognized entity and is characterized by pancarditis and marked tropism of spirochetes for cardiac tissues.

Zika Virus Infection Among U.S. Pregnant Travelers - August 2015-February 2016.

After reports of microcephaly and other adverse pregnancy outcomes in infants of mothers infected with Zika virus during pregnancy, CDC issued a travel alert on January 15, 2016, advising pregnant women to consider postponing travel to areas with active transmission of Zika virus. On January 19, CDC released interim guidelines for U.S. health care providers caring for pregnant women with travel to an affected area, and an update was released on February 5. As of February 17, CDC had received reports of nine pregnant travelers with laboratory-confirmed Zika virus disease; 10 additional reports of Zika virus disease among pregnant women are currently under investigation. No Zika virus-related hospitalizations or deaths among pregnant women were reported. Pregnancy outcomes among the nine confirmed cases included two early pregnancy losses, two elective terminations, and three live births (two apparently healthy infants and one infant with severe microcephaly); two pregnancies (approximately 18 weeks' and 34 weeks' gestation) are continuing without known complications. Confirmed cases of Zika virus infection were reported among women who had traveled to one or more of the following nine areas with ongoing local transmission of Zika virus: American Samoa, Brazil, El Salvador, Guatemala, Haiti, Honduras, Mexico, Puerto Rico, and Samoa. This report summarizes findings from the nine women with confirmed Zika virus infection during pregnancy, including case reports for four women with various clinical outcomes. U.S. health care providers caring for pregnant women with possible Zika virus exposure during pregnancy should follow CDC guidelines for patient evaluation and management. Zika virus disease is a nationally notifiable condition. CDC has developed a voluntary registry to collect information about U.S. pregnant women with confirmed Zika virus infection and their infants. Information about the registry is in preparation and will be available on the CDC website.

Transmission of Zika Virus Through Sexual Contact with Travelers to Areas of Ongoing Transmission - Continental United States, 2016.

Zika virus is a flavivirus closely related to dengue, West Nile, and yellow fever viruses. Although spread is primarily by Aedes species mosquitoes, two instances of sexual transmission of Zika virus have been reported, and replicative virus has been isolated from semen of one man with hematospermia. On February 5, 2016, CDC published recommendations for preventing sexual transmission of Zika virus. Updated prevention guidelines were published on February 23. During February 6-22, 2016, CDC received reports of 14 instances of suspected sexual transmission of Zika virus. Among these, two laboratory-confirmed cases and four probable cases of Zika virus disease have been identified among women whose only known risk factor was sexual contact with a symptomatic male partner with recent travel to an area with ongoing Zika virus transmission. Two instances have been excluded based on additional information, and six others are still under investigation. State, territorial, and local public health departments, clinicians, and the public should be aware of current recommendations for preventing sexual transmission of Zika virus, particularly to pregnant women. Men who reside in or have traveled to an area of ongoing Zika virus transmission and have a pregnant partner should abstain from sexual activity or consistently and correctly use condoms during sex with their pregnant partner for the duration of the pregnancy.

Update: Interim Guidelines for Health Care Providers Caring for Infants and Children with Possible Zika Virus Infection--United States, February 2016.

CDC has updated its interim guidelines for U.S. health care providers caring for infants born to mothers who traveled to or resided in areas with Zika virus transmission during pregnancy and expanded guidelines to include infants and children with possible acute Zika virus disease. This update contains a new recommendation for routine care for infants born to mothers who traveled to or resided in areas with Zika virus transmission during pregnancy but did not receive Zika virus testing, when the infant has a normal head circumference, normal prenatal and postnatal ultrasounds (if performed), and normal physical examination. Acute Zika virus disease should be suspected in an infant or child aged <18 years who 1) traveled to or resided in an affected area within the past 2 weeks and 2) has ≥2 of the following manifestations: fever, rash, conjunctivitis, or arthralgia. Because maternal-infant transmission of Zika virus during delivery is possible, acute Zika virus disease should also be suspected in an infant during the first 2 weeks of life 1) whose mother traveled to or resided in an affected area within 2 weeks of delivery and 2) who has ≥2 of the following manifestations: fever, rash, conjunctivitis, or arthralgia. Evidence suggests that Zika virus illness in children is usually mild. As an arboviral disease, Zika virus disease is nationally notifiable. Health care providers should report suspected cases of Zika virus disease to their local, state, or territorial health departments to arrange testing and so that action can be taken to reduce the risk for local Zika virus transmission. As new information becomes available, these guidelines will be updated: http://www.cdc.gov/zika/.

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.

Update: Interim Guidelines for Health Care Providers Caring for Pregnant Women and Women of Reproductive Age with Possible Zika Virus Exposure - United States, 2016.

CDC has updated its interim guidelines for U.S. health care providers caring for pregnant women during a Zika virus outbreak (1). Updated guidelines include a new recommendation to offer serologic testing to asymptomatic pregnant women (women who do not report clinical illness consistent with Zika virus disease) who have traveled to areas with ongoing Zika virus transmission. Testing can be offered 2-12 weeks after pregnant women return from travel. This update also expands guidance to women who reside in areas with ongoing Zika virus transmission, and includes recommendations for screening, testing, and management of pregnant women and recommendations for counseling women of reproductive age (15-44 years). Pregnant women who reside in areas with ongoing Zika virus transmission have an ongoing risk for infection throughout their pregnancy. For pregnant women with clinical illness consistent with Zika virus disease,* testing is recommended during the first week of illness. For asymptomatic pregnant women residing in areas with ongoing Zika virus transmission, testing is recommended at the initiation of prenatal care with follow-up testing mid-second trimester. Local health officials should determine when to implement testing of asymptomatic pregnant women based on information about levels of Zika virus transmission and laboratory capacity. Health care providers should discuss reproductive life plans, including pregnancy intention and timing, with women of reproductive age in the context of the potential risks associated with Zika virus infection.

Two Distinct Yersinia pestis Populations Causing Plague among Humans in the West Nile Region of Uganda.

Plague is a life-threatening disease caused by the bacterium, Yersinia pestis. Since the 1990s, Africa has accounted for the majority of reported human cases. In Uganda, plague cases occur in the West Nile region, near the border with Democratic Republic of Congo. Despite the ongoing risk of contracting plague in this region, little is known about Y. pestis genotypes causing human disease.

Interim Guidelines for Prevention of Sexual Transmission of Zika Virus - United States, 2016.

Zika virus is a mosquito-borne flavivirus primarily transmitted by Aedes aegypti mosquitoes (1,2). Infection with Zika virus is asymptomatic in an estimated 80% of cases (2,3), and when Zika virus does cause illness, symptoms are generally mild and self-limited. Recent evidence suggests a possible association between maternal Zika virus infection and adverse fetal outcomes, such as congenital microcephaly (4,5), as well as a possible association with Guillain-Barré syndrome. Currently, no vaccine or medication exists to prevent or treat Zika virus infection. Persons residing in or traveling to areas of active Zika virus transmission should take steps to prevent Zika virus infection through prevention of mosquito bites (http://www.cdc.gov/zika/prevention/).

Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study.

Lyme borreliosis is the most common tick-borne disease in the northern hemisphere. It is a multisystem disease caused by Borrelia burgdorferi sensu lato genospecies and characterised by tissue localisation and low spirochaetaemia. In this study we aimed to describe a novel Borrelia species causing Lyme borreliosis in the USA.

Effectiveness of Residential Acaricides to Prevent Lyme and Other Tick-borne Diseases in Humans.

In the northeastern United States, tick-borne diseases are a major public health concern. In controlled studies, a single springtime application of acaricide has been shown to kill 68%-100% of ticks. Although public health authorities recommend use of acaricides to control tick populations in yards, the effectiveness of these pesticides to prevent tick bites or human tick-borne diseases is unknown.

Amelioration of murine sickle cell disease by nonablative conditioning and γ-globin gene-corrected bone marrow cells.

Patients with severe sickle cell disease (SCD) are candidates for gene therapy using autologous hematopoietic stem cells (HSCs), but concomitant multi-organ disease may contraindicate pretransplant conditioning with full myeloablation. We tested whether nonmyeloablative conditioning, a regimen used successfully for allogeneic bone marrow transplantation of adult SCD patients, allows engraftment of γ-globin gene-corrected cells to a therapeutic level in the Berkeley mouse model of SCD. Animals transplanted according to this regimen averaged 35% engraftment of transduced hematopoietic stem cells with an average vector copy < 2.0. Fetal hemoglobin (HbF) levels ranged from 20 to 44% of total hemoglobin and approximately two-thirds of circulating red blood cells expressed HbF detected by immunofluorescence (F-cells). Gene therapy treatment of SCD mice ameliorated anemia, reduced hyperleukocytosis, improved renal function, and reduced iron accumulation in liver, spleen, and kidneys. Thus, modest levels of chimerism with donor cells expressing high levels of HbF from an insulated γ-globin lentiviral vector can improve the pathology of SCD in mice, thereby illustrating a potentially safe and effective strategy for gene therapy in humans.

Notes from the Field: Increase in Human Cases of Tularemia--Colorado, Nebraska, South Dakota, and Wyoming, January-September 2015.

Tularemia is a rare, often serious disease caused by a gram-negative coccobacillus, Francisella tularensis, which infects humans and animals in the Northern Hemisphere. Approximately 125 cases have been reported annually in the United States during the last two decades. As of September 30, a total of 100 tularemia cases were reported in 2015 among residents of Colorado (n = 43), Nebraska (n = 21), South Dakota (n = 20), and Wyoming (n = 16) (Figure). This represents a substantial increase in the annual mean number of four (975% increase), seven (200%), seven (186%) and two (70%) cases, respectively, reported in each state during 2004-2014.