Human Granulocytic Ehrlichiosis in Northern California: Two Case Descriptions with Genetic Analysis of the Ehrlichiae

Foley, Janet E.; Crawford-Miksza, Leta; Dumler, J. Stephen; Glaser, Carol; Chae, Joon; Yeh, Elaine; Schnurr, David P.; Hood, Ron; Hunter, Willard; Madigan, John E.

doi:10.1086/520220

Cited by 43 publications

(15 citation statements)

References 22 publications

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“…This strain has been found previously in dogs, cats, and I. ricinus ticks in Europe and is different from the variant with accession number U02521, which is usually regarded as pathogenic for humans (40). In line with the infection of two Californian patients with another 16S rRNA gene variant (23), this finding does not support the hypothesis that only strains with the prototype sequence U02521 are pathogenic in humans. Furthermore, according to earlier studies (8,9,12,71), the phylogeny inferred from 16S rRNA gene sequences was not meaningful, indicating that this However, upon analyzing the ankA gene sequences we found them to separate into four clearly distinct clusters.…”

Section: Discussioncontrasting

confidence: 64%

Distinct Host Species Correlate with Anaplasma phagocytophilum ankA Gene Clusters

et al. 2011

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Anaplasma phagocytophilum is a Gram-negative, tick-transmitted, obligate intracellular bacterium that elicits acute febrile diseases in humans and domestic animals. In contrast to the United States, human granulocytic anaplasmosis seems to be a rare disease in Europe despite the initial recognition of A. phagocytophilum as the causative agent of tick-borne fever in European sheep and cattle. Considerable strain variation has been suggested to occur within this species, because isolates from humans and animals differed in their pathogenicity for heterologous hosts. In order to explain host preference and epidemiological diversity, molecular characterization of A. phagocytophilum strains has been undertaken. Most often the 16S rRNA gene was used, but it might be not informative enough to delineate distinct genotypes of A. phagocytophilum. Previously, we have shown that A. phagocytophilum strains infecting Ixodes ricinus ticks are highly diverse in their ankA genes. Therefore, we sequenced the 16S rRNA and ankA genes of 194 A. phagocytophilum strains from humans and several animal species. Whereas the phylogenetic analysis using 16S rRNA gene sequences was not meaningful, we showed that distinct host species correlate with A. phagocytophilum ankA gene clusters.

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Section: Discussioncontrasting

confidence: 64%

Distinct Host Species Correlate with Anaplasma phagocytophilum ankA Gene Clusters

et al. 2011

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“…WA variants in Washington were different from A. phagocytophilum variants reported for sheep in Norway (32), two people in northern California (13), and llama-associated ticks (3).…”

Section: Vol 43 2005 a Phagocytophilum Variants In Dog Infections 799mentioning

confidence: 67%

Genetic Variants of Anaplasma phagocytophilum Infecting Dogs in Western Washington State

et al. 2005

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Eight dogs from western Washington State suspected of being infected with Anaplasma phagocytophilum because of the finding of morulae in peripheral blood neutrophils were studied for determination of the etiologic agent of disease. All cases were diagnosed between April 2003 and April 2004. Six of the eight dogs had no travel history during the 6 months prior to presentation. Two dogs had traveled within the Northwest United States and Canada. Fever, lethargy, and anorexia were the most common clinical signs in the dogs. Lymphopenia, thrombocytopenia, and an elevated activity of alkaline phosphatase in the serum were the most common laboratory findings. All dogs tested during the acute phase of clinical signs were seropositive for A. phagocytophilum antibodies but negative for Ehrlichia canis antibodies. PCR amplification and direct sequencing of portions of the 16S rRNA gene from the whole blood of all seven dogs that were tested yielded A. phagocytophilum after a comparison to bacterial sequences available in the GenBank database. Five genetic variants were identified based on one or two nucleotide differences in the 16S rRNA gene sequences at nucleotide positions 54, 84, 86, and 120. Individual dogs were infected with more than one variant. Treatment with doxycycline or tetracycline resulted in a rapid resolution of clinical signs. The occurrence of canine granulocytic anaplasmosis in western Washington State suggests that A. phagocytophilum infection should be considered in differential diagnoses of dogs presenting with lethargy, anorexia, fever, and lameness, particularly in the context of lymphopenia, thrombocytopenia, and increased serum alkaline phosphatase. The zoonotic importance of A. phagocytophilum should support an increase in surveillance for horses and people residing in this area.

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“…The impact of such A. phagocytophilum 16S rRNA gene variants has been a matter of debate. Apart from two HGE patients in California, who were infected with strains that had the same 16S rRNA gene sequences as isolates from sick horses (19), all other cases of HGE were, to our knowledge, caused by strains with the 16S rRNA gene prototype sequence. Otherwise, A. phagocytophilum 16S rRNA gene variants have been shown to elicit diseases in horses (11), in roe deer (46), and in sheep (47).…”

Section: Discussionmentioning

confidence: 87%

High Diversity ofankASequences ofAnaplasma phagocytophilumamongIxodes ricinusTicks in Germany

Loewenich¹,

Baumgarten²,

Schröppel³

et al. 2003

J Clin Microbiol

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In Germany humans with acute granulocytic ehrlichiosis have not yet been described. Here, we characterized three different genes of Anaplasma phagocytophilum strains infecting German Ixodes ricinus ticks in order to test whether they differ from strains in other European countries and the United States. A total of 1,022 I. ricinus ticks were investigated for infection with A. phagocytophilum by nested PCR and sequence analysis. Forty-two (4.1%) ticks were infected. For all positive ticks, parts of the 16S rRNA and groESL genes were sequenced. The complete coding sequence of the ankA gene could be determined in 24 samples. The 16S rRNA and groESL gene sequences were as much as 100% identical to known sequences. Fifteen ankA sequences were >99.37% identical to sequences derived from humans with granulocytic ehrlichiosis in Europe and from a horse with granulocytic ehrlichiosis in Germany. Thus, German I. ricinus ticks most likely harbor A. phagocytophilum strains that can cause disease in humans. Nine additional sequences were clearly different from known ankA sequences. Because these newly described sequences have never been obtained from diseased humans or animals, their biological significance is currently unknown. Based on this unexpected sequence heterogeneity, we propose to use the ankA gene for further phylogenetic analyses of A. phagocytophilum and to investigate the biology and pathogenicity of strains that differ in the ankA gene.

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Human Granulocytic Ehrlichiosis in Northern California: Two Case Descriptions with Genetic Analysis of the Ehrlichiae

Cited by 43 publications

References 22 publications

Distinct Host Species Correlate with Anaplasma phagocytophilum ankA Gene Clusters

Distinct Host Species Correlate with Anaplasma phagocytophilum ankA Gene Clusters

Genetic Variants of Anaplasma phagocytophilum Infecting Dogs in Western Washington State

High Diversity ofankASequences ofAnaplasma phagocytophilumamongIxodes ricinusTicks in Germany

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