EDITORIAL

New vector-transmitted pathogens  T. Avsi c-Zupanc Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia Article published online: 1 May 2015

 Corresponding author: T. Avsic-Zupanc, Institute of Microbiology and Immunology, Medical Faculty, Zaloska 4, 1000 Ljubljana, Slovenia E-mail: [email protected]

In recent decades, vector-borne diseases have emerged as a threat to global health. Vectors such as ticks, mosquitoes, sand flies and mammals are responsible for the transmission of various pathogens causing diseases in humans and animals. The occurrence of vector-borne pathogens, and thus the risk posed to humans and animals, greatly depends on the distribution of suitable vectors, which is influenced by climate factors, environmental conditions, and anthropogenic factors. The interplay and complexity of these heterogeneous factors is not yet completely understood [1]. Many vector-transmitted pathogens have been introduced into new regions, and some endemic vector-borne diseases have increased in incidence. Several new pathogens have been discovered, and outbreaks of new clinical syndromes have been identified. Molecular methods have significantly contributed to the increased number of recently recognized microorganisms transmitted by vectors. Some of these newly identified microorganisms are readily linked to human disease, whereas others are not yet known to cause disease in humans, or have been recognized as human pathogens years after their discovery. In the current themed section of CMI, four articles describe the discovery of new vector-transmitted pathogens. The first contribution concerns severe fever with thrombocytopenia syndrome (SFTS), a newly discovered emerging infectious disease caused by a novel phlebovirus, named SFTS virus, transmitted to humans and animals by ticks. The second article gives an overview of another tick-borne pathogen, Candidatus Neoehrlichia mikurensis, an intracellular bacterium that has only recently been implicated as a causative agent of neoehrlichiosis. The third article reports on a relapsing fever group spirochete, Borrelia miyamotoi, which has been known to be transmitted by ixodid tick species for two decades, but only recently have human cases of infection with B. miyamotoi been found. The fourth article describes the relevance of Plasmodium knowlesi, a mosquito-borne blood parasite of the Southeast Asian macaques that has entered the human population.

Dexin Li reviews SFTS that has been discovered in China. This emerging disease presents with high fever, thrombocytopenia, leukopenia, and gastrointestinal disorders, and a high case-fatality rate was first recognized in rural areas of China in 2009 [2,3]. The viral aetiology of the disease was confirmed by isolation of a novel phlebovirus from patients with acute disease. A new virus, designated SFTS virus, is a member of the family Bunyaviridae, genus Phlebovirus. The disease was recently reported in Japan and South Korea [4,5], and another, genetically closely related phlebovirus, Heartland virus, was found to be the causative agent in cases with severe illness with thrombocytopenia in the USA [6]. Although ticks are generally considered to be the vector of SFTS, person-to-person transmission through direct contact with contaminated blood has also been reported [7]. SFTS varies in severity from mild to severe disease, including neurological manifestations, haemorrhages, and multi-organ failure with disseminated intravascular coagulation. The case-fatality rate is as high as 17%, and the majority of SFTS deaths in China have occurred in the elderly [8]. The disease can be clinically confused with other infectious diseases, including human granulocytic anaplasmosis and haemorrhagic fever with renal syndrome. Currently, there is no specific treatment other than supportive therapy. The author concludes that there is a need for specific antiviral drugs and protective vaccines, as SFTS is difficult to control, owing to the complex transmission chain between ticks, vertebrates and ticks in a changing environment [9]. Two interesting examples of reversed disease discovery, i.e. the identification of disease cases years after the vector-borne microorganism was first recognized, include C. Neoehrlichia mickurensis and B. miyamotoi [10]. C. Neoehrlichia mikurensis is a newly emerging tick-transmitted pathogen that belongs to the genus Neoehrlichia in the Anaplasmataceae family. As the bacterium has not been cultivated so far, its life cycle, morphology and cellular tropism are mainly presumed. In her review, Wennerås comprehensively describes the epidemiology of C. Neoehrlichia mickurensis infection among several species of ticks and rodents in Europe and Asia, where rodents seems to be its natural host reservoirs [11]. The first description of human infection with C. Neoehrlichia mikurensis appeared a decade after the microorganism was initially detected in ticks

Clin Microbiol Infect 2015; 21: 611–613 Clinical Microbiology and Infection © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved http://dx.doi.org/10.1016/j.cmi.2015.04.016

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[12]. Now, this bacterium causes neoehrlichiosis, which, in immunocompromised patients, may have a severe course, with vascular and thromboembolic involvement [13]. Treatment with doxycycline usually leads to the rapid and full recovery of patients. Finally, the author concludes that much about C. Neoehrlichia mikurensis remains unexplained, so successful culture of the bacterium is needed. Another tick-transmitted bacterium that has recently been recognized as a human pathogen is B. miyamotoi. This relapsing fever group spirochete was discovered 20 years ago in ixodid ticks in Japan, and later in other tick species that are known vectors of Lyme disease in Europe and the USA [14,15]. In the present themed section, Krause et al. show how the bacterium was ‘unattractive’ until the first human cases of B. miyamotoi infection were reported 4 years ago in Russia; subsequently, additional cases were discovered in Europe, Asia, the USA, and Japan [16,17]. The clinical manifestations of B. miyamotoi infection are non-specific, except for relapsing fever. Symptoms usually resolve after a week of specific therapy that includes commonly used antibiotics, which are also used for the treatment of Lyme disease. The authors suggest that the same preventive measures that are used for other tick-transmitted diseases should be effective for B. miyamotoi [17]. In the last article of this themed issue, Cox-Singh and Millar show how it has recently become evident that P. knowlesi, a parasite that characteristically infects forest macaque monkeys, can be transmitted to humans by mosquitoes [18]. Since the first discovery of human natural infection with P. knowlesi in 2004 in the Sarawak state of Borneo, this type of malaria has become the most prevalent in Malaysia, and is widespread in Southeast Asia [19,20]. The transmission cycle of this parasite is zoonotic and is restricted to the habitat of the natural hosts and vectors; thus, humans entering jungle settings are at risk. Until molecular methods became routinely available, human infections with P. knowlesi were misdiagnosed as infection with the morphologically similar Plasmodium malariae. Malaria caused by the former organism presents with a spectrum of clinical disease, including severe, complicated forms. Although the disease can be potentially fatal, P. knowlesi malaria can be successfully treated with antimalarial drugs [21]. The authors critically conclude that the natural transmission of P. knowlesi is under pressure because of its ongoing entry into the human population; therefore, permanent monitoring of transmission and host-switch events is necessary.

Transparency declaration The authors state that no potential conflict of interest exists.

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References [1] Kilpatrick AM, Randolph SE. Drivers, dynamics, and control of emerging vector-borne zoonotic diseases. Lancet 2012 Dec 1;380(9857):1946–55. [2] Xu B, Liu L, Huang X, Ma H, Zhang Y, Du Y, et al. Metagenomic analysis of fever, thrombocytopenia and leukopenia syndrome (FTLS) in Henan Province, China: discovery of a new bunyavirus. PLoS Pathog 2011 Nov;7(11):e1002369. [3] Yu XJ, Liang MF, Zhang SY, Liu Y, Li JD, Sun YL, et al. Fever with thrombocytopenia associated with a novel bunyavirus in China. N Engl J Med 2011 Apr 21;364(16):1523–32. [4] Takahashi T, Maeda K, Suzuki T, Ishido A, Shigeoka T, Tominaga T, et al. The first identification and retrospective study of severe fever with thrombocytopenia syndrome in Japan. J Infect Dis 2014 Mar;209(6):816–27. [5] Kim KH, Yi J, Kim G, Choi SJ, Jun KI, Kim NH, et al. Severe fever with thrombocytopenia syndrome, South Korea, 2012. Emerg Infect Dis 2013 Nov;19(11):1892–4. [6] Pastula DM, Turabelidze G, Yates KF, Jones TF, Lambert AJ, Panella AJ, et al. Notes from the field: heartland virus disease—United States, 2012–2013. MMWR Morb Mortal Wkly Rep 2014 Mar 28;63(12): 270–1. [7] Gai Z, Liang M, Zhang Y, Zhang S, Jin C, Wang SW, et al. Person-toperson transmission of severe fever with thrombocytopenia syndrome bunyavirus through blood contact. Clin Infect Dis 2012 Jan 15;54(2): 249–52. [8] Ding F, Guan XH, Kang K, Ding SJ, Huang LY, Xing XS, et al. Risk factors for bunyavirus-associated severe fever with thrombocytopenia syndrome, China. PLoS Negl Trop Dis 2014 Oct;8(10):e3267. [9] Li DX. Severe fever with thrombocytopenia syndrome: a newly discovered emerging infectious disease. Clin Microbiol Infect 2015;21: 614–20. [10] Tijsse-Klasen E, Koopmans MP, Sprong H. Tick-borne pathogen— reversed and conventional discovery of disease. Front Public Health 2014;2:1–8. 73. http://dx.doi.org/10.3389/fpubh.2014.00073. [11] Wennerås C. Infections with tick-borne bacterium ‘Candidatus Neoehrlichia mikurensis’. Clin Microbiol Infect 2015;21:621–30. [12] Welinder-Olsson C, Kjellin E, Vaht K, Jacobsson S, Wenneras C. First case of human ‘Candidatus Neoehrlichia mikurensis’ infection in a febrile patient with chronic lymphocytic leukemia. J Clin Microbiol 2010 May;48(5):1956–9. [13] von Loewenich FD, Geissdorfer W, Disque C, Matten J, Schett G, Sakka SG, et al. Detection of ‘Candidatus Neoehrlichia mikurensis’ in two patients with severe febrile illnesses: evidence for a European sequence variant. J Clin Microbiol 2010 Jul;48(7):2630–5. [14] Fukunaga M, Takahashi Y, Tsuruta Y, Matsushita O, Ralph D, McClelland M, et al. Genetic and phenotypic analysis of Borrelia miyamotoi sp. nov., isolated from the ixodid tick Ixodes persulcatus, the vector for Lyme disease in Japan. Int J Syst Bacteriol 1995 Oct;45(4): 804–10. [15] Crowder CD, Carolan HE, Rounds MA, Honig V, Mothes B, Haag H, et al. Prevalence of Borrelia miyamotoi in Ixodes ticks in Europe and the United States. Emerg Infect Dis 2014 Oct;20(10):1678–82. [16] Platonov AE, Karan LS, Kolyasnikova NM, Makhneva NA, Toporkova MG, Maleev VV, et al. Humans infected with relapsing fever spirochete Borrelia miyamotoi, Russia. Emerg Infect Dis 2011 Oct;17(10):1816–23. [17] Krause PJ, Fish D, Narasimhan S, Barbour AG. Borrelia miyamotoi infection in nature and in humans. Clin Microbiol Infect 2015;21: 631–9. [18] Cox-Singh J, Millar SB. Human infections with Plasmodium knowlesi— zoonotic malaria. Clin Microbiol Infect 2015;21:640–8.

Clinical Microbiology and Infection © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved, CMI, 21, 611–613

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Editorial

[19] Singh B, Kim Sung L, Matusop A, Radhakrishnan A, Shamsul SS, CoxSingh J, et al. A large focus of naturally acquired Plasmodium knowlesi infections in human beings. Lancet 2004 Mar 27;363(9414):1017–24. [20] Cox-Singh J. Zoonotic malaria: Plasmodium knowlesi, an emerging pathogen. Curr Opin Infect Dis 2012 Oct;25(5):530–6.

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[21] Daneshvar C, Davis TM, Cox-Singh J, Rafa’ee MZ, Zakaria SK, Divis PC, et al. Clinical and laboratory features of human Plasmodium knowlesi infection. Clin Infect Dis 2009 Sep 15;49(6):852–60.

Clinical Microbiology and Infection © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved, CMI, 21, 611–613

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