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PubMed2004

Human granulocytic ehrlichiosis in Europe.

Human granulocytic ehrlichiosis (HGE) is a tick-borne zoonosis caused by Anaplasma phagocytophilum. A MEDLINE literature search revealed that the European story of HGE began in 1995 with an article on the presence of serum antibodies to A. phagocytophilum. At present, there is seroepidemiological information indicating the presence of infection with HGE agent(s) for several European countries; seroprevalence rates range from zero or very low to up to 28%. The proportion of seropositive persons increases with age and is higher in persons exposed to ticks. Knowledge of the causative agent of HGE and of animal reservoirs in Europe is limited. Ixodes ricinus is a recognized vector of A. phagocytophilum in Europe. Prevalence of the agent in questing I. ricinus is usually higher in adult ticks than in nymphs and ranges from zero or very low to > 30%. Pronounced differences between countries and marked variability by localities were established. Up to March 2003 about 65 human patients (all but one were adults) with confirmed HGE and several patients fulfilling criteria for probable HGE had been reported. The majority of them came from Central Europe (Slovenia) and Scandinavia (Sweden) but there are individual reports from several other European countries. The patients presented with an acute febrile illness that as a rule occurred after a tick bite; the majority had leukopenia and/or thrombocytopenia, elevated concentration of C-reactive protein and mild abnormalities of liver function test results. A small number of patients does not permit reliable conclusions on the clinical features of European HGE; however, there is an impression that at least in central Europe (but maybe not in Scandinavia) the disease is, from the clinical angle, only mild to moderately severe and (most likely) self-limited. The relatively high proportion of the population with HGE serum antibodies and the presence of A. phagocytophilum (like) agent(s) in ticks, small mammals and deer as found in several European countries are discordant with the rather low number of patients with proven HGE. The discordance may indicate inadequate awareness among European physicians, limited recording and reporting of the disease, and/or the presence of and the infection of humans with nonpathogenic A. phagocytophilum (like) strains present in ticks. Additional studies are needed to better define the biological and public health significance of HGE in Europe.

Anaplasma phagocytophilum↗

PubMed2006

Vector seasonality, host infection dynamics and fitness of pathogens transmitted by the tick Ixodes scapularis.

Fitness of tick-borne pathogens may be determined by the degree to which their infection dynamics in vertebrate hosts permits transmission cycles if infective and uninfected tick stages are active at different times of the year. To investigate this hypothesis we developed a simulation model that integrates the transmission pattern imposed by seasonally asynchronous nymphal and larval Ixodes scapularis ticks in northeastern North America, with a model of infection in white-footed mice (Peromyscus leucopus) reservoir hosts, using the bacteria Borrelia burgdorferi and Anaplasma phagocytophilum as examples. In simulations, survival of microparasites, their sensitivity to reduced rodent and tick abundance, and to 'dilution' by a reservoir-incompetent host depended on traits that allowed (i) highly efficient transmission from acutely-infected hosts, (ii) long-lived acute or 'carrier' host infections, and/or (iii) transmission amongst co-feeding ticks. Minimum values for transmission efficiency to ticks, and duration of host infectivity, necessary for microparasite persistence, were always higher when nymphal and larval ticks were seasonally asynchronous than when these instars were synchronous. Thus, traits influencing duration of host infectivity, transmission efficiency to ticks and co-feeding transmission are likely to be dominant determinants of fitness in I. scapularis-borne microparasites in northeastern North America due to abiotic forcings influencing I. scapularis seasonality.

Anaplasma phagocytophilum↗

PubMed2003

Acarological risk of exposure to agents of tick-borne zoonoses in the first recognized Italian focus of Lyme borreliosis.

Acarological risk was calculated as the probability of encountering at least one host-seeking Ixodes ricinus tick infected by the pathogen Borrelia burgdorferi sensu lato, in 100 m transects in the province of Genoa, Italy. The seasonal pattern of I. ricinus was studied using generalized estimating equations (GEE) with negative binomial error, to consider overdispersion of tick counts and repeated sampling of the same dragging sites from April 1998 to March 1999. Prevalence of infection by B. burgdorferi s.l. was evaluated by PCR and hybridization with genospecies-specific probes. Acarological risk (R) peaked in April (R = 0.2, 95% CI 0.13-0.26) and November (R = 0.29, 95% CI 0.10-0.46). Borrelia garinii and B. valaisiana were the most common genospecies at our study site suggesting a major role of birds as reservoirs. DNA from Anaplasma phagocytophilum, the agent of granulocytic ehrlichiosis in humans and animals, was amplified from an adult I. ricinus.

Anaplasma↗

PubMed2005

Tick species and tick-borne infections identified in population from a rural area of Spain.

To determine the tick species that bite humans in the province of Soria (Spain) and ascertain the tick-borne pathogens that threaten people's health in that province, 185 tick specimens were collected from 179 patients who sought medical advice at health-care centres. The ticks were identified, and their DNA examined by PCR for pathogens. Most ticks were collected in autumn and spring (59 and 57 respectively). Nine species of ticks were identified, the most frequent being Dermacentor marginatus (55.7%), Ixodes ricinus (12.4%) and Rhipicephalus bursa (11.9%). Ninety-seven females, 66 males, 21 nymphs and one larva were identified. Twenty-six ticks carried DNA from Rickettsia spp. (11 Rickettsia slovaca, 6 Rickettsia spp. RpA4/DnS14, 1 Rickettsia massiliae/Bar29, and 8 unidentified); two ticks carried DNA from Borrelia burgdorferi sensu lato and seven ticks harboured DNA from Anaplasma phagocytophilum.

Anaplasma phagocytophilum↗

PubMed1997

Variations in seroprevalence and host factors for bovine anaplasmosis in Illinois.

The modified card agglutination test (MCAT) was used to detect antibodies to Anaplasma marginale in 4994 samples collected from market cattle through the Brucellosis Eradication Program in Illinois. The MCAT reactor rate in the sample was 6.4%. The statewide prevalence estimate increased to between 7.1% and 10.7% when corrected for sampling distribution and test sensitivity and specificity. While the sample reactor rate measures the proportion of infected cattle moving through the market system and into new herds, consideration of the sampling proportions and test characteristics is important when estimating the overall prevalence. Cows were found to be at decreased risk relative to male cattle in lower-prevalence areas, but the risk was similar in higher-prevalence areas. In both higher- and lower-prevalence areas, the risk for seropositivity increased from 1 year of age onwards, but the rate of increase with age was greater in the higher-prevalence areas. Calves, however, had higher seroprevalence levels than 1-2-year-old animals. The risk was highest for Angus and Angus-Hereford cross cattle, while dairy cattle showed a decreased risk in the whole sample, but not when the analyses were stratified by prevalence level. There was a higher concentration of dairy cattle in areas with lower prevalence levels.

Age Factors↗

PubMed1980

Collection and sterilization of large volumes of bovine serum and its use in vaccines against bovine babesiosis and anaplasmosis.

A method is described for the collection and sterilization of 100 1 batches of bovine serum. Serum was prepared by defibrination of 20 1 volumes of whole blood using an impeller spinning at 400-500 rev./min. After freezing and thawing the raw serum was clarified through milk filters, pre-filtered through cartridge filters and sterilized by membrane filtration. The bacteriologically sterile serum was used in vaccines against bovine babesiosis and anasplasmosis after testing indicated no toxicity for Babesia and Anaplasma.

Anaplasma↗

PubMed2002

Human granulocytic ehrlichiosis in Europe.

Ehrlichiosis comprises a group of emerging tick-borne infectious diseases caused by obligate intracellular Gram-negative bacteria that infect leukocytes. Infections caused by members of the genus Ehrlichia have been described in animals and humans, but to date there are no convincing reports of the presence of other types of human ehrlichiosis different from human granulocytic ehrlichiosis (HGE) in Europe. The European vector is the same as that of Lyme borreliosis, the hard tick Ixodes ricinus, and HGE has a similar epidemiology to that of Borrelia burgdorferi infection. Across Europe, I. ricinus is infected to a variable extent (0.4-66.7%) with the causative agent Ehrlichia (Anaplasma) phagocytophila genogroup, and since its first description in Slovenia in 1997, details of 15 patients have been published. Diagnosis requires careful consideration of all circumstances and symptoms (history of tick bite and the presence of a flu-like syndrome with variable degrees of anemia, thrombocytopenia, and leukopenia, and elevated liver enzymes). Some differences can be seen between US and European HGE patients. European HGE cases have a less severe course, and the presence of morulae is uncommon. In Europe, verification of HGE has been based on PCR and immunofluorescence antibody tests, because no isolation from humans has been reported.

Anaplasma phagocytophilum↗

PubMedDate not supplied

Epidemiology of bovine tick-borne diseases in southern Italy.

This investigation was carried out in an area covering part of three southern Italian regions: Campania, Basilicata and Apulia. Eighty-one farms were involved using the formula suggested by Thrusfield; they were equally distributed over the area which was subdivided into 81 geo-referenced sub-areas. In May and June 1999 from a total of 506 cattle, older than 18 months, blood-samples were taken and ticks were collected and identified. Serum samples were tested for antibodies of Bahesia bigemina, Babesia bovis and Anaplasma marginale with an ELISA technique. Eight farms (9.8%) out of the 81 examined were positive for B. bigemina only, 3 (3.7%) for A. marginale only, and 70 (86.4%) for both. None of the animals of any farm was found to be positive for B. bovis. Out of the 506 sera tested, 117 (23.1 %) were positive for B. bigemina only, 58 (11.5%) forA. marginale only and 250 (49.4%) for both species; 81 (16.0%) were negative for all of them. Ticks were collected on animals on 62 (76.5%) out of the 81 farms. Adult ticks (1 410) were collected and identified; the highest number belonged to the Rhipicephalus bursa species (65.5%), followed by Rhipicephalus turanicus (8.6) and Haemaphysalis punctata (8.4). The results showed that B. bigemina, A. marginale and their potential vectors are common in the area examined and indicated that there is a risk for animals imported from tick-borne disease-free areas.

Anaplasma↗

PubMedDate not supplied

Broad-range PCR-TTGE for the first-line detection of bacterial pathogen DNA in ticks.

Ticks are known or suspected vectors for a wide range of bacterial pathogens. One of the first steps for tick-borne risk assessment is the detection of these pathogens in their vectors. In the present study, a broad-range PCR amplification of the eubacterial gene encoding the 16S rRNA gene combined with Temporal Temperature Gradient gel Electrophoresis (TTGE) was evaluated as a method allowing the one-step detection of bacterial pathogen DNA in ticks. Firstly, DNA extracts from bacteria known to be tick-borne pathogens, i.e., Borrelia burgdorferi lato sensu, Anaplasma phagocytophilum, Spotted Fever Group (SFG) Rickettsia spp., were used to establish a TTGE pathogen DNA reference marker. Secondly, we used broad-range PCR-TTGE to detect the presence of DNA from these three pathogens in 55 DNA extracts from pools of 10 nymphal Ixodes ricinus ticks, which have been previously shown to carry DNA from at least one of those bacteria by specific PCR. Among the 20 B. burgdorferi specific-PCR samples, 15 (75%) were also found to be positive using PCR-TTGE. Sixteen of the seventeen (94%) Rickettsia spp. PCR-specific samples were positive using PCR-TTGE detection and all PCR-specific positive extracts (11/11, 100%) for A. phagocytophilum were also positive using PCR-TTGE. Moreover, we identified unexpected bacterial sequences that were not related to any of the three pathogens such as a sequence related to Spiroplasma sp. Thus, broad-range PCR-TTGE allowed the single step detection of DNA from up to 3 pathogens in the same co-infected samples as well as detection of DNA from unexpected bacteria.

Anaplasma phagocytophilum↗

PubMed2004

Comparison of patients fulfilling criteria for confirmed and probable human granulocytic ehrlichiosis.

In order to assess the validity of definitions for human granulocytic ehrlichiosis (HGE), epidemiological, clinical and laboratory findings for 13 patients with confirmed HGE and 21 patients fulfilling criteria for probable HGE were compared. The patients were identified during a prospective study on the aetiology of febrile illness occurring after a tick bite, performed in Slovenia from 1995 to 2002. Significant differences between the 2 groups were found for age of patients, duration of fever before the first examination, and several clinical and laboratory parameters including the occurrence of chills, myalgia, arthralgia, leukopenia, thrombocytopenia, abnormal liver function tests results, and elevated concentration of C-reactive protein. All the abnormalities were established more often in patients with confirmed HGE than in those with probable HGE. Patients with confirmed HGE exhibited higher geometric mean titre values and higher peak antibody titres to Anaplasma phagocytophilum that developed later in the course of their illness. The differences indicate that in some patients fulfilling criteria for probable HGE the signs and symptoms most probably are not the result of a recent infection with A. phagocytophilum.

Adult↗

PubMed1965

The nature of bands in parasitized bovine erythrocytes.

Anaplasma marginale is the etiological agent of a hemolytic disease of cattle, known as anaplasmosis. The organism appears as a marginal inclusion in parasitized erythrocytes, but certain isolates also have bands associated with the inclusion. Inclusions and associated bands in parasitized erythrocytes in the liver and peripheral circulation were studied by light microscope cytochemistry and electron microscopy. Bands were comet- and dumbbell-shaped by light microscopy and were stained by techniques used to demonstrate protein and fibrin. The same forms, as well as other shapes, were seen in infected erythrocytes which were sectioned and examined by electron microscopy. Bands had longitudinal and transverse periodicity. They did not appear to have a crystalline structure. Their appearance was collated with that of bovine fibrin. Bands were well differentiated in erythrocytes that were entensively hemolyzed by natural or artificial means, but poorly differentiated in mildly hemolyzed erythrocytes. Hemolysis methods appeared to influence the morphology of bands and their demonstration.

Anaplasma↗

PubMed2003

Prospective study of coinfection in patients with erythema migrans.

The frequency of coinfection with Borrelia burgdorferi and either Anaplasma phagocytophila or Babesia microti among patients with erythema migrans, the initial skin lesion of Lyme disease, was assessed in 2 mainland locations in Rhode Island and Connecticut in a 4-year prospective study. Of the 93 patients with culture-proven erythema migrans, 2 (2%) patients had coinfection with A. phagocytophila and 2 (2%) had coinfection with B. microti. We concluded that the frequency of coinfection with these agents was low among patients with erythema migrans in the study areas.

Adult↗

PubMed2003

Human anaplasmosis presenting as atypical pneumonitis in France.

Human anaplasmosis is a febrile illness caused by Anaplasma phagocytophilum, an intracellular bacterium transmitted by Ixodes ticks in the United States and Europe. Although cough is reported in 30% of the American cases, interstitial pneumonitis has been noted only once. Of the 9 confirmed cases reported in Europe, 3 presented with atypical pneumonitis. A. phagocytophilum should be added to the list of agents responsible for interstitial pneumonitis, especially in areas where human anaplasmosis is endemic.

Anaplasma phagocytophilum↗

PubMed2002

Diagnosis of human granulocytic ehrlichiosis: state of the art.

Human granulocytic ehrlichiosis is an emerging zoonosis caused by Anaplasma phagocytophilum and transmitted through the bite of infected Ixodes scapularis. It is prevalent in the Midwest and Northeast United States and also in Europe, and it presents as a nonspecific febrile illness a few days after a tick bite usually between late spring and fall. Most cases present in adult patients with a mild form of the disease, although it can be severe with multiorgan failure, particularly in the elderly and in the immunocompromised. Routine laboratory abnormalities include leukopenia with a left shift, lymphopenia, and thrombocytopenia. These abnormalities are more frequently present during the first week of illness and then tend to normalize; therefore their absence should not exclude the diagnosis. Specific tests to confirm the diagnosis during the acute phase include microscopic detection of morulae in granulocytes, culture of A. phagocytophilum, and polymerase chain reaction. Of these methods, culture appears to have the greatest sensitivity during the acute phase prior to antimicrobial treatment. Serology has an important role in the confirmation of the diagnosis when used in paired specimens and when high cutoff titers by indirect fluorescence antibody assay (> or = 640) are used to diagnose a recent infection.

Anaplasma phagocytophilum↗

PubMed2006

Pathogens and host DNA in Ixodes ricinus nymphal ticks from a German forest.

Unfed nymphs of Ixodes ricinus were collected from vegetation in a forest on the outskirts of Berlin, Germany and were analyzed for host and pathogen DNA. Pathogens were detected in 47% of the ticks. Borrelia afzelii was the commonest pathogen detected, followed by Rickettsia helvetica. Other pathogens included B. valaisiana, B. garinii, B. burgdorferi sensu stricto, Anaplasma phagocytophilum, and a relapsing fever-like Borrelia. Most of the host DNA detected was of rodent origin and was associated with infection by B. afzelii, R. helvetica, and A. phagocytophilum. Bird DNA was associated with B. valaisiana and B. garinii, and ruminant DNA with A. phagocytophilum. B. afzelii was also found in two ticks that contained bird DNA.

Anaplasma phagocytophilum↗

PubMed2006

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↗

PubMed2004

Bacterial responses to neutrophil phagocytosis.

PURPOSE OF REVIEW: This review focuses on adaptive bacterial interactions with neutrophils, emphasizing information communicated within the past year about bacterial factors that respond to contact with or phagocytosis by PMN. RECENT FINDINGS: Since the discovery of type III and IV secretion, progress in the analysis of bacterial interactions with host phagocytes has been extensive but largely focused on the macrophage. The remarkable growth of information about bacterial subversion of macrophage metabolism has been summarized in several excellent reviews. The scope of progress on neutrophil-bacteria interactions is more limited and dominated by recent studies of the granulocyte pathogen, Anaplasma phagocytophilum, the agent of granulocytic ehrlichiosis. SUMMARY: For many pathogens, contact with or ingestion by phagocytes elicits a vigorous but varied microbial response. The response repertoire includes activation of type III and type IV secretion systems that inject effector molecules into the host cell. Effectors modify host cell signaling and metabolic pathways to favor survival of the microbe. Whereas microbial secretory structures are few in kind and relatively conserved, effector molecules are numerous and variable. Effectors may promote phagocytosis by nonphagocytic cells or suppress phagocytosis by macrophages and neutrophils. They may suppress assembly or misdirect localization of the phagocyte NADPH oxidase that is responsible for generating toxic oxidants, and they may suppress phagosome-lysosome fusion. Phagocytosed bacteria may also up-regulate the expression of defensive proteins that attenuate the effects of phagocyte-derived antimicrobial toxins. These pathogenic stratagems probably have their origins in the competition among single-celled organisms, eukaryotes versus prokaryotes, that arose early in evolution.

Anaplasma phagocytophilum↗

PubMed1997

Seasonal prevalence of ticks and tick-transmitted haemoparasites in traditionally managed N'Dama cattle with reference to strategic tick control in the Gambia.

A survey of tick spatial and seasonal distribution in traditional managed N'Dama cattle over 1 year old was carried out in The Gambia over 16 months. Presence of Anaplasma marginale and Babesia spp. in the blood smears and their antibodies in the serum of same animals were also examined. Tick species, in decreasing order of abundance, were: Boophilus geigy, Rhipicephalus senegalensis, B.decoloratus, Hyalaomma truncatum, H.marginatum rufipes and Amblyomma variegatum. All tick species peaked during the rainy season. Additional B.geigy peaks occurred towards the end of the dry season. The most infested animal body areas were anogenital, udder and abdomen. A.variegatum, Hyalomma spp. and, to a lesser extent, Boophilus spp. showed strong preferences for these anatomical regions. Overall prevalence of A.marginale, B.bigemina and B.bovis haemoparasites were 3.2%, 0.9% and 0.1%, respectively. Peaks of A.marginale and B.bigemina occurred at the end of the rainy season-beginning of the dry season; an additional A.marginale peak was observed at mid-end dry season. Overall antibody seroprevalence were 29.6% for A.marginale, 44.7% for B.bigemina and 5.2% for B.bovis; monthly fluctuations in percentage of seroreactors were limited. Endemic stability for A.marginale and B.bigemina is postulated. Implications of the outcomes are discussed in relation to tick-control strategy in The Gambia.

Anaplasma↗