Tick-Borne Diseases.

Ticks are responsible for the vast majority of vector-borne illnesses in the United States. The number of reported tick-borne disease (TBD) cases has more than doubled in the past 20 years. The majority of TBD cases occur in warm weather months in individuals with recent outdoor activities in wooded areas. The risk of contracting a TBD is also highly dependent on geographic location. Between 24 and 48 hours of tick attachment is required for most disease transmission to occur. Only 50% to 70% of patients with a TBD will recall being bitten by a tick, and TBDs are often initially misdiagnosed as a viral illness. Most TBDs are easily treated when diagnosed early in their course.

Anaplasma, Ehrlichia and Rickettsia species infections in cats: European guidelines from the ABCD on prevention and management

OVERVIEW: Anaplasma species, Ehrlichia species and Rickettsia species are vector-borne pathogens infecting a wide variety of mammals, but causing disease in very few of them. Infection in cats: Anaplasma phagocytophilum is the most important feline pathogen among these rickettsial organisms, and coinfections are possible. Little information is available on the pathogenesis of these agents in cats. Clinical signs are usually reported soon after tick infestation. They are mostly non-specific, consisting of fever, anorexia and lethargy. Joint pain may occur. Infection in humans: Some rickettsial species ( A phagocytophilum, Ehrlichia chaffeensis, Ehrlichia ewingii, Rickettsia conorii, Rickettsia rickettsii, Rickettsia felis, Rickettsia typhi and Candidatus Neoehrlichia mikurensis) are of zoonotic concern. Direct contact with cat saliva should be avoided because of potential contamination by R felis. Infected cats are 'sentinels' of the presence of rickettsial pathogens in ticks and fleas in a given geographical area, and they signal a risk for people exposed to vectors.

Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis - United States.

Tickborne rickettsial diseases continue to cause severe illness and death in otherwise healthy adults and children, despite the availability of low-cost, effective antibacterial therapy. Recognition early in the clinical course is critical because this is the period when antibacterial therapy is most effective. Early signs and symptoms of these illnesses are nonspecific or mimic other illnesses, which can make diagnosis challenging. Previously undescribed tickborne rickettsial diseases continue to be recognized, and since 2004, three additional agents have been described as causes of human disease in the United States: Rickettsia parkeri, Ehrlichia muris-like agent, and Rickettsia species 364D. This report updates the 2006 CDC recommendations on the diagnosis and management of tickborne rickettsial diseases in the United States and includes information on the practical aspects of epidemiology, clinical assessment, treatment, laboratory diagnosis, and prevention of tickborne rickettsial diseases. The CDC Rickettsial Zoonoses Branch, in consultation with external clinical and academic specialists and public health professionals, developed this report to assist health care providers and public health professionals to 1) recognize key epidemiologic features and clinical manifestations of tickborne rickettsial diseases, 2) recognize that doxycycline is the treatment of choice for suspected tickborne rickettsial diseases in adults and children, 3) understand that early empiric antibacterial therapy can prevent severe disease and death, 4) request the appropriate confirmatory diagnostic tests and understand their usefulness and limitations, and 5) report probable and confirmed cases of tickborne rickettsial diseases to public health authorities.

Tick-Borne Illnesses.

Tick-borne diseases are prevalent throughout the United States. These illnesses are caused by a variety of different pathogens that use ticks as vectors, including bacteria, viruses, rickettsia, and protozoa. Some of the most common illnesses caused by ticks are Lyme disease, Rocky Mountain spotted fever, babesiosis, ehrlichiosis, anaplasmosis, tularemia, Colorado tick fever, tick-borne relapsing fever, and Powassan disease. Unique skin changes, fever, and influenza-like symptoms may indicate tick-borne disease. Early diagnosis can be difficult as well as nonspecific and can resemble overtraining syndrome. Diagnosis is important to facilitate early treatment to decrease morbidity and mortality and should often be initiated before a definitive diagnosis is made. Treatment guidelines are published by the Centers for Disease Control and Prevention. As tick-borne diseases increase and their geographic regions expand, it is important for providers to distinguish the often overlapping and diverse presentations of these diseases.

Recognition of and Prompt Treatment for Tick-Borne Infections in Children.

Tick-borne infections create diagnostic challenges because they tend to present with nonspecific findings. Because clinicians often fail to recognize tick-borne illnesses in early stages, therapy is frequently delayed or omitted. This is especially problematic for rickettsial infections (Rocky Mountain spotted fever, ehrlichiosis, and anaplasmosis), because the risk of long-term morbidity and mortality increases with delayed treatment. We emphasize the need for clinicians to maintain a high index of suspicion for tick-borne infections; to diagnose these illnesses presumptively, without waiting for confirmatory laboratory test results; and to promptly start therapy with doxycycline, even in young children, when rickettsial infections are suspected.

[Actual diagnosis, treatment and prevention of human granulocytic anaplasmosis]. / Aktualne postqpowanie diagnostyczne, terapeutyczne i prewencyjne w ludzkiej anaplazmozie granulocytarnej.

Ixodes ricinus tick is widely known as a reservoir and vector for many dangerous pathogens. One of them is gram-negative bacteria called Anaplasma phagocytophilum, that may cause human granulocytic anaplasmosis (formerly called granulocytic ehrlichiosis). Development of modem diagnostics, which allows the implementation of effective pharmacotherapy, caused that this disease can be effectively detected only for last couple years. Human granulocytic anaplasmosis in most cases is not a severe ailment, but in some patients, especially improperly diagnosed and treated, it can lead to serious complications or even death. Due to non-specific clinical symptoms and a small number of laboratories proceeding specialized tests, human granulocytic anaplasmosis constitutes clinical and diagnostic problem. A significant increase in tick-borne diseases needs to increase public and physicians awareness of these issues.

Rhabdomyolysis-induced acute kidney injury secondary to Anaplasma phagocytophilum and concomitant statin use.

We report the case of a patient with rhabdomyolysis-induced acute renal failure occurring in the setting of Anoplasma phagocytophilum infection based on the presence of morulae in neutrophils and concomitant statin use. Although the pathogenesis is unknown, we believe the combination of concurrent statin use in the setting of the infection promoted this complication. We describe proposed mechanisms including cytokine activation, alteration of the muscle membrane components, and ionic balance as contributing factors.

Molecular and cellular pathobiology of Ehrlichia infection: targets for new therapeutics and immunomodulation strategies.

Ehrlichia are small obligately intracellular bacteria in the order Rickettsiales that are transmitted by ticks and associated with emerging life-threatening human zoonoses. Vaccines are not available for human ehrlichiosis, and therapeutic options are limited to a single antibiotic class. New technologies for exploring host-pathogen interactions have yielded recent advances in understanding the molecular interactions between Ehrlichia and the eukaryotic host cell and identified new targets for therapeutic and vaccine development, including those that target pathogen virulence mechanisms or disrupt the processes associated with ehrlichial effector proteins. Animal models have also provided insight into immunopathological mechanisms that contribute significantly to understanding severe disease manifestations, which should lead to the development of immunomodulatory approaches for treating patients nearing or experiencing severe disease states. In this review, we discuss the recent advances in our understanding of molecular and cellular pathobiology and the immunobiology of Ehrlichia infection. We identify new molecular host-pathogen interactions that can be targets of new therapeutics, and discuss prospects for treating the immunological dysregulation during acute infection that leads to life-threatening complications.

Ehrlichia-induced hemophagocytic lymphohistiocytosis in two children.

Two children presented with a history of fever and rash. Lab values revealed pancytopenia, elevated ferritin, coagulopathy, and elevated triglycerides. Both children quickly developed respiratory distress and hypotension requiring admission to the ICU. Bone marrow biopsies revealed hemophagocytosis. Studies for Ehrlichia returned positive. The patients were started on doxycycline and treated for hemophagocytic lymphohistiocytosis (HLH). Each made a full recovery. In both patients, testing for MUNC and perforin genes were found to have no mutation. These two cases demonstrate the importance of considering Ehrlichiosis as a possible trigger of HLH.

Human ehrlichiosis and anaplasmosis.

Human ehrlichiosis and anaplasmosis are acute febrile tick-borne diseases caused by various members of the genera Ehrlichia and Anaplasma (Anaplasmataceae). Human monocytotropic ehrlichiosis has become one of the most prevalent life-threatening tick-borne disease in the United States. Ehrlichiosis and anaplasmosis are becoming more frequently diagnosed as the cause of human infections, as animal reservoirs and tick vectors have increased in number and humans have inhabited areas where reservoir and tick populations are high. Ehrlichia chaffeensis, the etiologic agent of human monocytotropic ehrlichiosis (HME), is an emerging zoonosis that causes clinical manifestations ranging from a mild febrile illness to a fulminant disease characterized by multiorgan system failure. Anaplasma phagocytophilum causes human granulocytotropic anaplasmosis (HGA), previously known as human granulocytotropic ehrlichiosis. This article reviews recent advances in the understanding of ehrlichial diseases related to microbiology, epidemiology, diagnosis, pathogenesis, immunity, and treatment of the 2 prevalent tick-borne diseases found in the United States, HME and HGA.

Rickettsial and ehrlichial infections.

Rickettsial diseases represent a clinically homogeneous group of infections characterized by fever, headache myalgias, variable presence of a rash, and a broad spectrum of neurological manifestations. Epidemiological information including time of year, geography, history of arthropod exposure, and animal contact gives important clues to the diagnosis, and should be actively elicited. Abnormalities in hematological indices of liver function tests should also increase suspicion for illness. Delay in initiation of doxycycline therapy while awaiting laboratory confirmation of infection has been associated with progressive neurological impairment and death. Clinicians should maintain a low threshold to initiate empiric therapy for rickettsial diseases in any patient with neurological findings and compatible exposures, signs, or laboratories, as these syndromes represent readily treatable causes of neurological dysfunction.

Current management of human granulocytic anaplasmosis, human monocytic ehrlichiosis and Ehrlichia ewingii ehrlichiosis.

Anaplasma phagocytophilum, Ehrlichia chaffeensis and Ehrlichia ewingii are emerging tick-borne pathogens and are the causative agents of human granulocytic anaplasmosis, human monocytic ehrlichiosis and E. ewingii ehrlichiosis, respectively. Collectively, these are referred to as human ehrlichioses. These obligate intracellular bacterial pathogens of the family Anaplasmataceae are transmitted by Ixodes spp. or Amblyomma americanum ticks and infect peripherally circulating leukocytes to cause infections that range in clinical spectra from asymptomatic seroconversion to mild, severe or, in rare instances, fatal disease. This review describes: the ecology of each pathogen; the epidemiology, clinical signs and symptoms of the human diseases that each causes; the choice methods for diagnosing and treating human ehrlichioses; recommendations for patient management; and is concluded with suggestions for potential future research.

[Ehrlichiosis/Anaplasmosis]. / Ehrlichióza/Anaplazmóza.

Ehrlichiosis and anaplasmosis are zoonoses caused by bacteria from the family Anaplasmataceae, including human and animal pathogens. The human pathogens are Ehrlichia chaffeensis, the causative agent of human monocytic ehrlichiosis (HME), Anaplasma phagocytophilum, the pathogen causing human granulocytic anaplasmosis (HGA), E. ewingii and Neorickettsia sennetsu, granulocytotropic and monocytotropic Ehrlichia species, respectively. Ehrlichia spp. are small, gram-negative, obligate intracellular bacteria. They replicate in the cytoplasmic vacuoles of host cells, especially granulocytes and monocytes, to form microcolonies called morulae. These agents are transmitted through the bite of infected tick. In the United States, the vectors are Amblyomma americanum, Ixodes scapularis and Ixodes pacificus ticks. The primary vector in Europe is Ixodes ricinus. Rodents, deer, roe deer, foxes, cattle, sheep, goats, horses and dogs are reservoirs of these bacteria in Europe. Peromyscus leucopus, the white-footed mouse, and Odocoileus virginianus, the white-tailed deer, are the most important reservoirs in the United States. Infection in humans is manifested as a nonspecific flu-like illness. The laboratory diagnosis is most frequently serological--evidence of antibody by indirect immunofluorescence assay (IFA) and detection of DNA by polymerase chain reaction (PCR), or microscopy evidence--Giemsa stain of blood smears (morulae in granulocytes or monocytes). Doxycycline is the drug of choice in therapy. Avoiding exposure to ticks is the best method of prevention of infection.

Rickettsial and other tick-borne infections.

Tick bites are best prevented by people avoiding tick-infested areas. When this is not possible, tick bites may be prevented by the wearing of long trousers that are tucked into boots. The best method to avoid tick bites is twofold: application of a topical deet (N,N-diethyl-m-toluamide) repellent to exposed skin, and treatment of clothing with permethrin. This system is currently used by the US Army to protect soldiers. Ticks can crawl underneath clothing and bite untreated portions of the body; therefore, treating clothing is imperative. Permethrin is nontoxic to humans, and can be used in any age group. Permethrin is commercially available. Checking clothing regularly while in tick-infested areas is highly recommended to back up the few hours of protection provided by the insect repellents. It is also recommended that the entire body be carefully screened for ticks and other parasites by campers and hunters while they are staying in and after leaving infested areas. Any tick found should be removed immediately. Removing ticks may not be easy. It is best to use blunt, rounded forceps, and a magnifying glass to remove ticks, especially when immature ticks are found. The forceps are used to grasp the mouthparts of the tick as close as possible to the skin, and then the tick is pulled upward, perpendicular to the skin, with a continuous and steady action. Usually any mouth parts of the tick retained in the skin are eliminated uneventfully by the body. Other methods of removing ticks, such as using fingers, lighted cigarettes, petroleum jelly, or suntan oil, should be avoided. Killing the tick in situ may increase the risk of regurgitation by the tick and the transmission of infectious agents. Most stick bites are uncomplicated, and result only in benign cutaneous inflammatory reactions that may be pruritic for a few days. As a result of mouthparts being retained at the feeding site, a granuloma may rarely develop. There are no data to indicate that antimicrobial prophylaxsis is beneficial to the tick-bitten patient to prevent disease. It must be kept in mind that the risk of transmission of disease increases with the duration of attachment and generally requires greater than 24 to 48 hours. The degree of tick engorgement or the time since tick exposure and discovery of the tick may be used to establish the likely duration of attachment and the risk of disease transmission. Reducing and controlling tick populations is difficult. Habitat modifications, including vegetation management by cutting, burning, and herbicide treatment, and drainage of wet areas are one strategy for tick control, but their effects are often short-lived, and they can cause severe ecologic damage. Chemicals used to control ticks may cause environmental contamination, and therefore, toxicity for humans and animals. Biologic control methods for ticks include the promotion of natural predators. Natural predators of ticks are beetles, spiders, and ants, and parasites such as insects, mites and nematodes. Tick control is best based on the concept of integrated pest management, in which different control methods are adapted to one area or against one tick species with due consideration to their environmental effects. Tick-borne diseases are increasing in prevalence. Perhaps it is because people are undertaking more outdoor activities, which result in contact with ticks and their pathogens. Clinicians should be aware of the clinical sign of tick-transmitted diseases, because morbidity and mortality as a result of these diseases increases substantially if there are delays in diagnosis and treatment. Tick-borne illness occur in distinctive geographic areas. The reporting of these illnesses and diseases to the health department enables the gathering of information and statistics. The public should be informed about the risks of disease in tick-infested areas and the means of preventing infections. The most common diseases are caused by Rickettsia, Borrelia, and Ehrichia, but with continued study, new pathogens and diseases will continue to emerge.

Clinical diagnosis and treatment of human granulocytotropic anaplasmosis.

Tick-borne rickettsiae in the genera Ehrlichia and Anaplasma are intracellular bacteria that infect wild and domestic mammals and, more recently, man. The increased desire of humans for recreational activities outdoors has increased the exposure to potential human pathogens that previously cycled almost exclusively within natural, nonhuman enzootic hosts. Anaplasma phagocytophilum causes an acute, nonspecific febrile illness of humans previously known as human granulocytotropic ehrlichiosis (HGE) and now called human granulocytotropic anaplasmosis (HGA). The first patient to have recognized HGA was hospitalized at St Mary's Hospital in Duluth, Minnesota, USA in 1990. However, the clinical and laboratory presentation of this infection remained undefined until 1994, when Bakken and collaborators published their experience with 12 patients who had HGA. By the end of December 2004, at least 2,871 cases of HGA had been reported from 13 U.S. states to the Centers for Disease Control and Prevention (CDC). A limited number of laboratory-confirmed cases have been reported from countries in Europe, including Austria, Italy, Latvia, the Netherlands, Norway, Poland, Slovenia, Spain, and Sweden. Ixodes persulcatus-complex ticks are the arthropod hosts for Borrelia burgdorferi, the agent of Lyme borreliosis, and are also the arthropod hosts for A. phagocytophilum. Most cases of HGA have been contracted in geographic regions that are endemic for Lyme borreliosis. Male patients outnumber female patients by a factor of 3 to 1 and as many as 75% of patients with HGA have had a tick bite prior to their illness. Seroepidemiologic studies have demonstrated that HGA for the most part is a mild or even asymptomatic illness. However, older individuals and patients who are immunocompromised by natural disease processes or medications may develop an acute, influenza-like illness characterized by high fever, rigors, generalized myalgias, and severe headache. Local skin reactions at the site of the tick bite have not been described, and nonspecific skin rashes have been reported only occasionally. Anaplasmosis is associated with variable but suggestive changes in routine laboratory test parameters. Most patients develop transient reductions in total leukocyte and platelet concentrations. Relative granulocytosis accompanied by a left shift and lymphopenia during the first week of illness has been reported frequently. Serum hepatic transaminase concentrations usually increase two- to fourfold, and inflammatory markers, such as C-reactive protein and the erythrocyte sedimentation rate, rise during the acute phase. Abnormal laboratory findings may return toward normal range for patients who have been ill for more than 7 days, which may obfuscate the clinical decision making. Characteristic clusters of bacteria (morulae) are observed in the cytoplasm of peripheral blood granulocytes in 20% to 80% of infected patients during the acute phase of illness. The clinical diagnosis may be confirmed retrospectively by specific laboratory tests, which include positive polymerase chain reaction (PCR), identification of A. phagocytophilum in culture of acute-phase blood, or the detection of specific antibodies to A. phagocytophilum in convalescent serum. Virtually all patients have developed serum antibodies to A. phagocytophilum after completion of antibiotic therapy, and demonstration of seroconversion by indirect immunofluorescent antibody testing of acute-phase and convalescent-phase serum samples is currently the most sensitive and specific tool for laboratory confirmation of HGA. Treatment with doxycycline usually results in rapid improvement and cure. Most patients with HGA have made an uneventful recovery even without specific antibiotic therapy. However, delayed diagnosis in older and immunocompromised patients may place those individuals at risk for an adverse outcome, including death. Thus, prompt institution of antibiotic therapy is advocated for any patient who is suspected to have HGA and for all patients who have confirmed HGA.

Enteritis and colitis in horses.

Enteritis and colitis remain challenging and life-threatening diseases despite many recent advances. Successful treatment is largely dependent on early recognition and directed therapy, which is facilitated by obtaining a complete history and physical examination. A number of new therapies and methods of monitoring critically ill patients have become integral components of treatment success. The critical monitoring of equine foals and adults continues to be an exciting and emerging field.

Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever, ehrlichioses, and anaplasmosis--United States: a practical guide for physicians and other health-care and public health professionals.

Tickborne rickettsial diseases (TBRD) continue to cause severe illness and death in otherwise healthy adults and children, despite the availability of low cost, effective antimicrobial therapy. The greatest challenge to clinicians is the difficult diagnostic dilemma posed by these infections early in their clinical course, when antibiotic therapy is most effective. Early signs and symptoms of these illnesses are notoriously nonspecific or mimic benign viral illnesses, making diagnosis difficult. In October 2004, CDC's Viral and Rickettsial Zoonoses Branch, in consultation with 11 clinical and academic specialists of Rocky Mountain spotted fever, human granulocytotropic anaplasmosis, and human monocytotropic ehrlichiosis, developed guidelines to address the need for a consolidated source for the diagnosis and management of TBRD. The preparers focused on the practical aspects of epidemiology, clinical assessment, treatment, and laboratory diagnosis of TBRD. This report will assist clinicians and other health-care and public health professionals to 1) recognize epidemiologic features and clinical manifestations of TBRD, 2) develop a differential diagnosis that includes and ranks TBRD, 3) understand that the recommendations for doxycycline are the treatment of choice for both adults and children, 4) understand that early empiric antibiotic therapy can prevent severe morbidity and death, and 5) report suspect or confirmed cases of TBRD to local public health authorities to assist them with control measures and public health education efforts.

Tick-borne infections in children: epidemiology, clinical manifestations, and optimal management strategies.

Ticks can transmit bacterial, protozoal, and viral infections to humans. Specific therapy is available for several of these infections. Doxycycline is the antimicrobial treatment of choice for all patients, regardless of age, with Rocky Mountain spotted fever, human monocytic ehrlichiosis, or human granulocytic ehrlichiosis. Chloramphenicol has been used to treat these infections in children but is demonstrably inferior to doxycycline. In patients with Mediterranean spotted fever, doxycycline, chloramphenicol, and newer macrolides all appear to be effective therapies. Therapy of Lyme disease depends on the age of the child and stage of the disease. For early localized disease, amoxicillin (for those aged <8 years) or doxycycline (for those aged >/=8 years) is effective. Doxycycline, penicillin V (phenoxymethylpenicillin) or penicillin G (benzylpenicillin) preparations, and erythromycin are all effective treatments for tick-borne relapsing fever. Hospitalized patients with tularemia should receive gentamicin or streptomycin. Doxycycline and ciprofloxacin have each been investigated for the treatment of tularemia in outpatients; however, these agents do not yet have established roles in the treatment of this disease in children. Combination therapy with clindamycin and quinine is preferred for children with babesiosis; the combination of azithromycin and atovaquone also appears promising. Ribavirin has been recently shown to markedly improve survival in patients with Crimean-Congo hemorrhagic fever. The role of antiviral therapy in the treatment of other tick-borne viral infections, including other hemorrhagic fevers and tick-borne encephalitis, is not yet defined.

[Ehrlichiosis]. / Ehrlichioza.

Ehrlichiosis is a disease caused by Ehrlichiae bacteria. The disease is transmitted by ticks. The disease occurs in the following clinical forms: monocytic ehrlichiosis, granulocytic ehrlichiosis and sennetsu fever. Symptoms of ehrlichiosis are non-specific, and include flu-like symptoms, cutaneous manifestations (erythema), enlargement of the lymphatic nodules, liver and spleen. Involvement of the gastrointestinal tract is common in the patients. Symptoms are accompanied by alteration seen in peripheral blood (leukopenia with lymphocytopenia, thrombocytopenia). Antibiotics are used in management of ehrlichiosis.