| Tick-borne infectious diseases are a class of natural foci of disease, and most belong to emerging infectious diseases. As is known, many kinds of tick-borne pathogens, including viruses, rickettsiae, spirochetes, parasites, and bacteria have been identified. Due to the wide distribution of tick vectors and animal hosts, the infection of tick-borne pathogens is highly prevalent in nature. People might easily acuquire tickborne diseae through tick bites when they enter the nature foci, therefore, tick-borne diseases pose a serious healthy threat to the individuals who are engages in productive activities, economic development, and tourism in the natural world.Anaplasma phagocytophilum, an obligate intracellular cytoplasmic bacteria and transmitted by ticks, can infect human granulocytes and cause human granulocytic anaplasmosis(HGA). The first human case of HGA was reported in the United States in 1994, and then the number of cases of HGA has steadily increased in the United States. HGA cases were also reported in Europe, including in the Netherlands, France, Germany, Italy, Denmark, Spain, Poland and other countries. In 2006, an outbreak of HGA was reported in Anhui Province of China. Serological surveys provided evidence of potential human cases of HGA in many areas in China. However, due to the lack of clinical recognization and difficulty in making molecular diagnosis, clinically confirmed cases were rarely reported. Several researches based on experimental animal models discussed pathogenic characteristics, but the exact infection mechanism is unclear. The pathogens from different regions have different genetic background, which might be related to different pathogenic characteristics. The pathogenic characteristics of A. phagocytophilum strains identified in China need to be studied.Due to the existence of a variety of tick-borne diseases in the natural foci, tick vectors or animal hosts could carry two or more pathogens, therefore human coinfections often occur. Coinfections with A. phagocytophilum and Borrelia burgdorferi, Borrelia burgdorferi and B. microti, or A. phagocytophilum and B. microti, are frequently seen among ticks, animals, and exposed population. Our previous research has found the coinfection of A. phagocytophilum, and B. microti from Rattus norvegicus in Xinyang city. The present study is designed to establish experimental animal models solely infected or coinfected with A. phagocytophilum and B. microti. Based on these models, the pattern of pathogen infection was explored and pathogenic characteristics were investigated.An epidemic of severe fever with thrombocytopenia syndrome(SFTS) was first identified in middle-eastern region in 2009, and has affected about 20 provinces, leading to thousands of symptomatic human infections since then. SFTS has been severely endemic in Xinyang city of Henan province. However, considering that ticks can carry a variety of pathogens and there are often multiple tick-borne diseases in one natural foci, the potential infection of other tick-borne pathogens could be presumed. Our preliminary study found the coinfection of A. phagocytophilum, and B. microti from rodents in Xinyang, suggesting that other tick-borne diseases might occurred in this area. Therefore, in order to learn more about the specific circumstances of tickborne diseases in Xinyang, we further investigated infection prevalence of A. phagocytophilum, B. microti, Spotted fever group rickettsiae( SFGR), and SFTS virus, in the tick vectors and local populations.The main results:1 Experimental infection study of A. phagocytophilum and B. microtiThe present study established experimental mouse models solely infected with A. phagocytophilum or B. microti and coinfected with the two pathogens, and investigated the pattern of pathogen infection and pathogenic characteristics.Bacteremia peaked 10 days after solely infected with A. phagocytophilum, then gradually decreased, and lasted about three months; parasitemia peaked 20 days after solely infected with B. microti, then rapidly declined, and lasted about three months. Both A phagocytophilum and B. microti infection could cause splenomegaly in Balb / C mices, and the splenomegaly gradually restored as the pathogen load reduced; Both A.phagocytophilum and B. microti infection could lead to leukopenia and thrombocytopenia, B microti infection could also cause erythropenia and decrease of hemoglobin levels. Both A. phagocytophilum and B. microti infection could cause slightly pathological changes of spleen, lung, and liver tissue in acute phase of infection.When coinfected with B. microti, the pathogen load of A. phagocytophilum could remain at high levels for prolonged duration; when previously infected with A.phagocytophilum, the peak of parasitemia occurred earlier, and the pathogen load increased to two fold as solely infection. Coinfection of phagocytophilum and B. microti could cause splenomegaly, leukopenia, thrombocytopenia, erythropenia, and decreased levels of hemoglobin, and lead to present pathological changes as observed in sole infections with either A.phagocytophilum or B. microti.2 Investigations on infections with A. phagocytophilum and other tick-borne pathogens in ticksFrom 2013 to 2015, a total of 658 adult Haemaphysalis longicornis ticks were collected in Xinyang city of Henan province and screened for infections with A. phagocytophilum and other tick-borne pathogens. The infection rate of A. phagocytophilum was 3.2%, and there is no significant difference between host-seeking ticks and engorged ticks. We also found that the presence of B. microti and SFGR infections in the ticks, with infection rates of 2.4% and 12.8%, respectively. SFTSV was also detected with a prevalence of detected% in H. longicornis ticks. Coinfections between A. phagocytophilum and B. microti, A. phagocytophilum and SFGR, and coinfections with B. microti and SFGR were determined in the ticks.3 Investigations on human infections with A. phagocytophilum and other tickborne pathogensSerological tests were performed in patients who were acutely symptomatic with fever and had a history of tick bites or animal contact within past one month. As a result, 17 patients had seroconversion or a four-fold titer increase of Ig G antibody against A. phagocytophilum, 11 patients had seroconversion or a four-fold titer increase of Ig G antibody against B. babesia, and 29 patients had seroconversion or a four-fold titer increase of Ig G antibody against R. ricketsii. Moreover, 12 patients were confirmed as past infection with A. phagocytophilum, 18 patients were confirmed as past infection with B. babesia, and 11 patients were confirmed as past infection with SFGR. Through PCR assays and sequence analyses of both omp A and glt A genes, two novel SFGR, Rickettsia sp. XY99 and Rickettsia sp. XY118, were identified.Similar clinical characteristics were found in the patients with A. phagocytophilum, B. microti, or SFGR infections, except that the patients with SFGR infection might have rash or eschar. The clinical results were not confirmatory due to a small patient number and the selection bias might be induced since the study was performed in a SFTS endemic region, where residence with SFTS like illness might be prone to seek medical care. In addition, to gain a complete clinical picture of the novel Rickettsia infection, a community based study is needed.The main conclusions:This study revealed difference of pathogen load and pathogenic characteristics of A. phagocytophilum sole infection, B. microti sole infection, and coinfections with two pathogens. The coinfection could cause complicated disease progression and might lead to more severe disease manifestations, necessitating the clinical vigilance to identify coinfectons of tick-borne pathogens.Through field surveys on ticks in Xinyang city of Henan province, we found the existence of A. phagocytophilum, B. microti, and SFGR in the area, and we also identified the coinfection of these tick-borne pathogens in ticks from the area. The findings suggested the potential infection of A. phagocytophilum or other tick-borne pathogens in people who were exposed to ticks.By serological tests, both acute infections and past infections of A. phagocytophilum, B. microti, and SFGR, were found in the patients who were acutely symptomatic with fever and had a history of tick bites or animal contact within past one month. Two novel SFGR species, Rickettsia sp. XY99 and Rickettsia sp. XY118, were identified in the acute blood samples collected from the patients who had positive serological test results. The findings indicated the existence of infections with A. phagocytophilum or other tick-borne pathogens in SFTS suspected patients, especially those who were negative for SFTSV infection. In addition, serological tests also found the coinfections with these pathogens, such as A. phagocytophilum and B. microti, A. phagocytophilum and SFGR, B. microti and SFGR. Among these patients, one was found acutely coinfected with A. phagocytophilum and B. microti. Since the previous studies suggest that the coinfection of the two pathogens could cause more complicated disease, clinical physicians need to pay more attention to the patients with A. phagocytophilum and B. microti coinfection. Further clinical investigations should be performed on more human cases to confirm the impact of the coinfection of tick-borne pathogens on disease progression and prognosis. |
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