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Dissociation between inhibition and killing by levofloxacin in human granulocytic anaplasmosis.

Human granulocytic anaplasmosis (HGA) is a potentially fatal tick-borne infection caused by Anaplasma phagocytophilum. Treatment options are limited for this entity, with doxycycline being the drug of choice. Certain fluoroquinolones such as levofloxacin are active against A. phagocytophilum in vitro. We report a hospitalized patient with HGA who improved coincident with a 13-day course of levofloxacin therapy, but clinically and microbiologically relapsed 15 days after completion of treatment. Relapse of infection after levofloxacin therapy was reproduced in a severe combined immune-deficient (SCID) mouse infection model. Quinolone therapy should not be considered curative of HGA.

Aged↗

Human granulocytic anaplasmosis affecting the myocardium.

A case of 65-year-old male is reported who presented with myalgias, headache, and fever. He subsequently developed myocarditis and was diagnosed to have anaplasmosis on peripheral blood smear. He was treated with doxycycline for 30 days. A coronary angiogram done after recovery showed normal epicardial arteries. The case illustrates the importance of a careful examination of the peripheral smear, with a high index of clinical suspicion, which led to prompt treatment and complete recovery of the patient.

Adult↗

Chemotherapy of acute bovine anaplasmosis.

The efficacy of a standard tetracycline, imidocarb and a new experimental long-acting tetracycline (T-200) in the treatment of anaplasmosis was examined in 5 groups of 9 nonsplenectomised, adult, 4-year-old, speyed cattle. The efficacy of T-200 was further examined using 9 splenectomised calves. One treatment of imidocarb (3.5 mg/kg) or T-200 (20 mg/kg) or 2 treatments (10 mg/kg) of a standard tetracycline were very effective in controlling the infection in the intact cattle. On inoculation of T-200 (20 mg/kg) controlled infection in 5 splenectomized calves, whereas all 4 untreated control calves died. T-200 did not sterilise either intact or splenectomised cattle.

Acute Disease↗

Bovine leucosis virus contamination of a vaccine produced in vivo against bovine babesiosis and anaplasmosis.

Contamination of a batch of tick fever (babesiosis and anaplasmosis) vaccine with bovine leucosis virus (BLV) was detected when a herd, in the final stages of an enzootic bovine leucosis (EBL) accreditation program, developed a large number of seropositive cattle following use of tick fever vaccine. Investigations incriminated a single calf used to produce Anaplasma centrale vaccine from which 13,959 doses were distributed. The failure of this calf to give a positive agar gel immunodiffusion (AGID) test before use was not fully explained. A total of 22,627 cattle from 111 herds receiving contaminated vaccine was tested to validate claims for compensation. Results showed infection rates of 62% and 51.8% in vaccinated dairy and beef cattle, respectively, compared with 6.1% and 1.5% in non-vaccinated cattle in the same herds. The results also indicated that infection did not spread from vaccinated to non-vaccinated in-contact cattle. Heavy reliance is now placed on purchase of calves for vaccine production from EBL accredited-free herds and on transmission tests from the calves to sheep to prevent a recurrence of contamination. The need for a BLV antigen detection test, with the sensitivity of the sheep transmission test but simpler and faster to perform, is evident.

Anaplasma↗

CXCR2 blockade influences Anaplasma phagocytophilum propagation but not histopathology in the mouse model of human granulocytic anaplasmosis.

Anaplasma phagocytophilum is an obligate intracellular bacterium that infects neutrophils and causes human granulocytic anaplasmosis. Infection induces neutrophil secretion of interleukin-8 or murine homologs and perpetuates infection by recruiting susceptible neutrophils. We hypothesized that antibody blockade of CXCR2 would decrease A. phagocytophilum tissue load by interrupting neutrophil recruitment but would not influence murine hepatic pathology. C3H-scid mice were treated with CXCR2 antiserum or control prior to or on day 14 after infection. Quantitative PCR and immunohistochemistry for A. phagocytophilum were performed and severity of liver histopathology was ranked. Control mice had more infected cells in tissues than the anti-CXCR2-treated group. The histopathological rank was not different between treated and control animals. Infected cells of control mice clustered in tissue more than in treated mice. The results support the hypothesis of bacterial propagation through chemokine induction and confirm that tissue injury is unrelated to A. phagocytophilum tissue load.

Anaplasma phagocytophilum↗

Innate immune tissue injury and murine HGA: tissue injury in the murine model of granulocytic anaplasmosis relates to host innate immune response and not pathogen load.

Anaplasma phagocytophilum is an obligate intracellular tick-borne bacterium that propagates within neutrophils and causes human and animal granulocytic anaplasmosis (HGA). In the murine model of HGA, host immune response plays a more important role in histopathologic lesions than does pathogen load. We examined the role of CYBB, NOS2, and TNFalpha as effectors of innate immune-related injury. Our hypothesis is that the innate immune response to A. phagocytophilum results in inflammatory histopathology, but does not control the pathogen.

Anaplasma phagocytophilum↗

Concentration of procalcitonin and C-reactive protein in patients with human granulocytic anaplasmosis and the initial phase of tick-borne encephalitis.

The aim of this prospective study was to assess the value of procalcitonin (PCT) level and serum concentration of C-reactive protein (CRP) in differentiating viral from bacterial infection in selected groups of patients, including those with acute human granulocytic anaplasmosis (HGA), which is caused by an intracellular bacteria Anaplasma phagocytophilum, and patients with the initial phase of tick-borne encephalitis (TBE), which is a viral disease caused by an RNA virus belonging to the Flavivirus genus of the family Flaviviridae.

Anaplasmosis↗

Molecular epidemiology of human and bovine anaplasmosis in southern Europe.

The genus Anaplasma (Rickettsiales: Anaplasmataceae) includes several pathogens such as A. marginale and A. phagocytophilum that have an impact on veterinary and human health. In this study, we characterized A. marginale and A. phagocytophilum infections in humans, wild and domestic animals, and ticks in southern Europe (particularly in south-central Spain and in Sicily) by means of serologic study, PCR, and sequence analysis of major surface proteins (msp) 1alpha and 4 and 16S rDNA. The results suggest that A. marginale infections in this region are maintained in cattle and deer, with ticks and tabanids serving as biological and mechanical vectors of the pathogen, respectively. Infections with A. phagocytophilum may occur in humans and are maintained in cattle, donkeys, deer, and birds and are most likely transmitted by several tick species with as yet an unknown role as reservoir hosts for other wild and domesticated mammals. The presence of concurrent infections in cattle and deer suggests that these pathogens may multiply in the same reservoir host and illustrates the complexity of the epidemiology of bovine and human anaplasmosis in this region.

Anaplasma↗

Human granulocytic anaplasmosis in northeastern Italy.

Sporadic cases of human granulocytic anaplasmosis (HGA) have been reported in areas with a high prevalence of tick-borne diseases (TBDs) in Europe. We aimed at estimating the sero-prevalence of A. phagocytophilum and other TBDs in northeastern Italy in outpatients with a history of recent tick bite or suspected TBD. In the 1-year study, 79 patients were enrolled and 30 (38%) received a diagnosis of TBD: 24 (30%) with Lyme disease and 5 (6%) with HGE. Our findings indicate the presence of HGA in northeastern Italy; so, since co-infection with Lyme disease appeared to be frequent, physicians assessing patients after a tick bite should consider HGA in the diagnosis.

Anaplasmosis↗

Human anaplasmosis: the first Spanish case confirmed by PCR.

We report a case of human anaplasmosis (HA) fulfilling the confirmation criteria: epidemiologic data and clinical picture compatible with HA; presence of a morulae within polymorphonuclear leukocyte; and positive PCR assay for Anaplasma phagocytophilum: This case report shows the presence of HA in Spain.

Adult↗

Molecular diagnosis of human granulocytic anaplasmosis.

Human granulocytic anaplasmosis, formerly known as human granulocytic ehrlichiosis, is caused by the microorganism Anaplasma phagocytophilum that is transmitted by Ixodes tick bites. The disease state ranges from subclinical to fatal but may be difficult to differentiate from other febrile conditions without specific tests. Rapid and early diagnosis is important since the infection may be fatal and specific antibiotic therapy is required. The bacterium is an obligate intracellular pathogen of neutrophils. Thus, early diagnosis is best achieved by amplification of nucleic acids from the blood. An increasing number of potential gene targets for diagnostic assays have been described and the incipient release of an Anaplasma phagocytophilum genome sequence will not only help to better understand the disease but may facilitate improvements in diagnostic strategies.

Anaplasma phagocytophilum↗

Perceived causes, diagnosis and treatment of babesiosis and anaplasmosis in cattle by livestock farmers in communal areas of the central Eastern Cape Province, South Africa.

Perceived causes, diagnosis and treatment of redwater (babesiosis) and gallsickness (anaplasmosis) in cattle by livestock farmers in communal areas of the central Eastern Cape Province were investigated by means of participatory methods, semi-structured interviews and a questionnaire survey. Most livestock owners relate the causes of these diseases to excessive grazing of lush green grass, which is thought to bring about an accumulation of bile in the body. The majority of livestock owners diagnose gallsickness and redwater on the basis of presenting signs and post mortem findings. Eighty nine percent of a total of 343 livestock owners participating in the study claimed to administer herbal remedies to treat the 2 tick-borne diseases; 75% of these combine herbal remedies with conventional medicines and 25% use herbal remedies only. Application of herbal remedies was reportedly aimed mainly at the removal of excess bile. However, some plant species used to prepare herbal remedies are reported to possess activities ranging from anti-inflammatory, analgesic, antimicrobial, anti-pyretic and purgative, and may be effective in the treatment of gallsickness and redwater. A lack of understanding of the causes and transmission of gallsickness and redwater, leading to ill-directed treatment, and widespread deviation from the directions of use when administering conventional medicines, were identified as problems that could be addressed by farmer training and the supply of appropriate information.

Anaplasmosis↗

The impact of 2 dipping systems on endemic stability to bovine babesiosis and anaplasmosis in cattle in 4 communally grazed areas in Limpopo Province, South Africa.

A 12-month study was conducted in 4 communal grazing areas in the Bushbuckridge region, Limpopo Province, South Africa. The main objective was to investigate the impact of reduced acaricide application on endemic stability to bovine babesiosis (Babesia bigemina and Babesia bovis) and anaplasmosis (Anaplasma marginale) in the local cattle population. To this end 60 cattle in each communal grazing area were bled at the beginning and the conclusion of the experimental period and their sera were assayed for B. bovis, B. bigemina and Anaplasma antibodies. Cattle in the intensively dipped group were dipped 26 times and maintained on a 14-day dipping interval throughout the study, whereas cattle in the strategically dipped group were dipped only 13 times. Three cattle, from which adult ticks were collected, were selected from each village, while immature ticks were collected by drag-sampling the surrounding vegetation. During the dipping process, a questionnaire aimed at assessing the prevalence of clinical cases of tick-borne disease, abscesses and mortalities was completed by an Animal Health Technician at each diptank. An increase in seroprevalence to B. bovis and B. bigemina and a decrease in seroprevalence to Anaplasma was detected in the strategically dipped group while in the intensively dipped group the converse was true. Amblyomma hebraeum was the most numerous tick species on the cattle, and Rhipicephalus (Boophilus) microplus was more plentiful than Rhipicephalus (Boophilus) decoloratus. Drag samples yielded more immature stages of A. hebraeum than of Rhipicephalus (Boophilus) spp. The incidence of clinical cases of tick-borne disease and of abscesses increased in the strategically dipped group at the start of the survey.

Anaplasma marginale↗

The modified card agglutination test: an accurate tool for detecting anaplasmosis in Columbian black-tailed deer.

Inoculation of susceptible calves confirmed that the modified card agglutination test accurately detected the anaplasmosis infection status of each of 35 Columbian black-tailed deer (Odocoileus hemionus columbianus). Anaplasma marginale, and specific antibodies, were demonstrated only in calves which received blood from deer that were positive by the card test. The modified card agglutination testing of deer serum was performed in the manner recommended for testing cattle serum with bovine-origin antigen and bovine serum factor.

Agglutination Tests↗

Immunization against anaplasmosis and babesiosis: Part I. Evaluation of immunization using minimum infective doses under laboratory conditions.

A method of immunization against anaplasmosis and babesiosis using minimum infective doses was developed under laboratory conditions. Stabilates of Anaplasma marginale stored at -60 degrees C were found infective when diluted 10-fold to 10(-3). Stabilates of Babesia argentina and Babesia bigemina stored under the same conditions were infective when diluted 10-fold to 10(-1). Intact calves inoculated with the above dilutions of stabilates developed moderate parasitemias and recovered from infection without treatment. There was an immune response to vaccination with the formation of specific antibodies to A. marginale, B. bigemina and B. argentina as measured by the complement fixation (CF) test. All calves were found resistant to artificial challenge with lethal doses of the respective parasites.

Anaplasmosis↗

Survey of anaplasmosis in elk of the Clearwater National Forest (Idaho).

Samples of blood from 27 free-roaming elk (Cervus canadensis canadensis) from the Clearwater National Forest in north central Idaho were tested by the rapid card agglutination test and complement-fixation test for the presence of antibodies against Anaplasma marginale. The serum card test and complement-fixation test gave incomplete and false-positive reactions; the plasma card test did not give any reactions. Anaplasma bodies or other blood parasites were not observed in stained smears of elk blood. Blood from 11 elk, including 2 that were serum card test-positive, did not produce clinical, hematologic, or serologic evidence of infection in 3 anaplasmosis-susceptible bovine calves.

Anaplasmosis↗

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.

Anaplasmosis↗