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Background Human granulocytic anaplasmosis (HGA) is a systemic inflammatory response caused by the rickettsial bacterium Anaplasma phagocytophilum. Rhabdomyolysis and acute kidney injury (AKI) are rare complications of HGA. Here, we report a case of HGA concurrent with rhabdomyolysis and AKI in an elderly patient. Case presentation An 84-year old woman with a medical history of hypertension was hospitalised after two days of fever, dizziness, whole body pain, and general weakness. Laboratory investigations showed severe thrombocytopenia, leukopenia, impaired renal function, and elevated cardiac enzyme and myoglobin levels. On the day after admission, peripheral blood smear revealed morula inclusions in neutrophils, a suggestive finding of HGA. Real-time polymerase chain reaction (PCR) results indicated the presence of A. phagocytophilum. Antibiotics were de-escalated to doxycycline monotherapy. After 10 days of antibiotic treatment, laboratory tests showed complete recovery from HGA complicated with rhabdomyolysis and AKI. Conclusions HGA can lead to serious complications in patients with associated risk factors. Therefore, in patients with HGA accompanied by rhabdomyolysis, management with antibiotics and hydration should be initiated immediately, and not delayed until diagnostic confirmation.

Anaplasma phagocytophilum is the agent of tick-borne fever, equine, canine and human granulocytic anaplasmosis. The common route of A. phagocytophilum transmission is through a tick bite, the main vector in Europe being Ixodes ricinus. Despite the apparently ubiquitous presence of the pathogen A. phagocytophilum in ticks and various wild and domestic animals from Europe, up to date published clinical cases of human granulocytic anaplasmosis (HGA) remain rare compared to the worldwide status. It is unclear if this reflects the epidemiological dynamics of the human infection in Europe or if the disease is underdiagnosed or underreported. Epidemiologic studies in Europe have suggested an increased occupational risk of infection for forestry workers, hunters, veterinarians, and farmers with a tick-bite history and living in endemic areas. Although the overall genetic diversity of A. phagocytophilum in Europe is higher than in the USA, the strains responsible for the human infections are related on both continents. However, the study of the genetic variability and assessment of the difference of pathogenicity and infectivity between strains to various hosts has been insufficiently explored to date. Most of the European HGA cases presented as a mild infection, common clinical signs being pyrexia, headache, myalgia and arthralgia. The diagnosis of HGA in the USA was recommended to be based on clinical signs and the patient’s history and later confirmed using specialized laboratory tests. However, in Europe since the majority of cases are presenting as mild infection, laboratory tests may be performed before the treatment in order to avoid antibiotic overuse. The drug of choice for HGA is doxycycline and because of potential for serious complication the treatment should be instituted on clinical suspicion alone.

[Background] The tick-borne intracellular pathogen, Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae) causes human granulocytic anaplasmosis after infection of polymorphonuclear leucocytes. The human Sp110 gene is a member of the nuclear body (NB) components that functions as a nuclear hormone receptor transcriptional coactivator and plays an important role in immunoprotective mechanisms against pathogens in humans. In this research, we hypothesized that Sp110 may be involved in the infection of human promyelocytic HL-60 cells with A. phagocytophilum., [Methods] The human Sp110 and A. phagocytophilum msp4 mRNA levels were evaluated by realtime RT-PCR in infected human HL-60 cells sampled at 0, 12, 24, 48, 72 and 96 hours postinfection. The effect of Sp110 expression on A. phagocytophilum infection was determined by RNA interference (RNAi). The expression of Sp110 was silenced in HL-60 cells by RNAi using predesigned siRNAs using the Nucleofector 96-well shuttle system (Amaxa Biosystems, Gaithersburg, MD, USA). The A. phagocytophilum infection levels were evaluated in HL-60 cells after RNAi by realtime PCR of msp4 and normalizing against human Alu sequences., [Results] While Sp110 mRNA levels increased concurrently with A. phagocytophilum infections in HL-60 cells, the silencing of Sp110 expression by RNA interference resulted in decreased infection levels., [Conclusion] These results demonstrated that Sp110 expression is required for A. phagocytophilum infection and multiplication in HL-60 cells, and suggest a previously undescribed mechanism by which A. phagocytophilum modulates Sp110 mRNA levels to facilitate establishment of infection of human HL-60 cells., This work was supported by the Oklahoma Agricultural Experiment Station (project 1669), the Sitlington Endowed Chair for Food Animal Research to K.M.K. and the Ministry of Science and Education (MEC), Spain (project AGL2005-07401). Dr. Raúl Manzano-Roman was funded by Ministerio de Educación y Ciencia, Spain. V. Naranjo was founded by Consejería de Educación, JCCM, Spain.

[Background] Anaplasma phagocytophilum causes human granulocytic anaplasmosis (HGA) in humans, which has been recognized as an emerging tick-borne disease in the United States and Europe. Although about 65 cases of HGA have been reported in Europe, some of them do not fulfill the criteria for confirmed HGA. Confirmation of HGA requires A. phagocytophilum isolation from blood, and/or identification of morulae in granulocytes and/or positive PCR results with subsequent sequencing of the amplicons to demonstrate specific rickettsial DNA. Seroconversion or at least fourfold increase in antibody titers to A. phagocytophilum has been used as criteria for confirmed HGA also., [Case presentation] Infection with A. phagocytophilum was confirmed by PCR in a patient in Sicily, Italy, who had negative serology for A. phagocytophilum. A fragment of A. phagocytophilum 16S rDNA was amplified by two independent laboratories and sequenced from two separate patient's blood samples. The 16S rDNA sequence was identical in both samples and identical to the sequence of the A. phagocytophilum strain USG3 originally obtained from a dog., [Conclusion] Infection with A. phagocytophilum was confirmed in a patient without a detectable antibody response against the pathogen. The results reported herein documented the first case of confirmed HGA in Sicily, Italy. These results suggested the possibility of human infections with A. phagocytophilum strains that result in clinical symptoms and laboratory findings confirmatory of HGA but without detectable antibodies against the pathogen., This research was supported by The Ministry of Health, Italy, the Instituto de Ciencias de la Salud (ICS-JCCM), Spain (project 03052-00) and the Endowed Chair for Food Animal Research and the Oklahoma Agricultural Experiment Station Project 1669 (K.M. Kocan). V. Naranjo is funded by Junta de Comunidades de Castilla–La Mancha (JCCM), Spain.

Vector borne diseases are classical emerging infectious diseases in human and animal populations. Ticks represent perfect vectors for number of bacteria, parasites and viruses. The genera Anaplasma, Ehrlichia and recently specified cluster ‘Candidatus Neoehrlichia’ comprise all bacteria from family Anaplasmataceae, transmitted by ixodid ticks to mammalian hosts causing infection in humans and animals. ‘Candidatus Neoehrlichia mikurensis’ is one of emrgening vector borne zoonosis recently recognized as human pathogen. First case of human infection was reported from Sweden in 2010 and up to now six human infections were described in Czech Republic, Germany and Switzerland. In 2011 first case of septicaemia in two dogs was reported indicating ability of Neoehrlichia to infect various mammalian species, while different rodent species may act as reservoir host. The aim of this study was to identify species from family Anaplasmataceae from different species of wild animals (851). The presence of selected pathogens from wild cervids, wild boars, small rodents, muflons, chamois, martens, bears, badgers, wolves, jackals and foxes were determined by performing PCR on spleen samples and subsequent sequencing of fragment of 16S rRNA gene. Sequence analysis revealed presence of N. mikurensis, two strains of Anaplasma phagocytophilum, Anaplasma centrale, A. bovis and Ehrlichia sp. Small rodents were infected mainly with N. mikurensis together with A. phagocytophilum. Neoehrlichia mikurensis was single species detected in wild boars, bears and badgers, which represent first finding in these mammalian species. In chamois all species have been found except A. bovis. Wild cervids were harbouring both strains of A. phagocytophilum, while muflons were infected with A. centrale, A. phagocytophilum, A. bovis and N. mikurensis. Martens and jackals were free from pathogens while sequencing failed in wolf samples. Foxes were infected with both strains of A. phagocytophilum and interestingly in single animal A. bovis was confirmed. Two isolates Ehrlichia sp. from roe deer and chamois were identical to Ehrlichia sp. from Sika deer from Japan. Data obtained from this study clearly present presence of two zoonotic pathogens: A. phagocytophilum, causative agent of human granulocytic anaplasmosis (HGA) and newly recognized pathogen N. mikurensis in various species. These results also imply importance of wildlife as potential reservoir for ticks and potential transmission to humans.