| BACKGROUNDTick-borne diseases are a series of zoonotic natural focus infection diseases infected hunman around the world. At present 33 kinds of tick-borne agents have been identified in China, including eight species of spotted fever group rickettsiae, seven species in the family Anaplasmataceae, six genospecies in th e complex Borrelia burgdorferi sensu lato, 11 species of Babesia, and the virus causing severe fever with thrombocytopenia syndrome. Four species of spotted fever group rickettsiae(R heilongjiangiensis, Candidatus R tarasevichiae, R sibirica sp BJ-90 and R raoultii) can infect human.From 2011 to 2014,a total of SFTS 5352 cases were reported in 23 provinces of China mainland. In the first five months of 2015, 523 SFTS cases have been reported. Numbers of patients in Xinyang city, Henan province rank first among all cirites with cases reported. At present treatment for SFTS was mostly symptomatic resolving. Studies have shown that ribavirin is effective, but some clinical studies reported the effectiveness of antibiotic, doxycycline in treating SFTS. It’s suggested there might be infection with other tick borne disease among clinical diagnosed SFTS patients.Haemaphysalis longicornis, as the SFTSV carrier in Xinyang city is the dominant species. In recent years, Zhou Xiaonong’s investigation in Xinyang city Henan province shows the co-infection of Rickettsia with other tick-borne pathogens in H.longicornis. Sun Yi has isolated R. monacensis from ticks captured in Xinyang. Both studies shows that there may be human’s infection with Rickettsia. OBJECTIVEIn this study we recruited SFTS patients in 154 Hospital of Xinyang City, Henan Province, in 2014. Monitoring of SFGR was carried out, aiming at discovering whether the CRT patients have infected with other tick-borne diseases. Learn to understand the feature of etiology, clinical manifestations and differences. Once positive cases are found, researches of SFGR natural foci should activate to figure out the epidemiology charcteristics of SFGR in central and eastern China. METHODPatients who had an acute fever(temperatures of 37.5°C or higher) with thrombocytopenia(platelet count < 100 × 109/L) and/or leukopenia(leukocyte count < 4.0 × 109/L) according to the criteria for suspected SFTS were enrolled in the study(7, 9). Molecular and serologic tests were performed to diagnose CRT and SFTS infection. Data regarding clinical manifestations and laboratory findings were retrieved from medical records. RESULTSThe first part :56 of 733 patients assessed were infected with CRT based on polymerase-chain-reaction and sequencing. The median age of the 56 patients was 59 years(range, 25 to 89 years) and 29(52%) were female. The median of interval between the onset of disease and admission to the hospital was 5 days, with an interquartile range(IQR) of 4 to 6 days. The median of hospitalization duration was 7 days(IQR, 4 to 9 days). All the 56 patients were farmers living in rural areas, distributed in 7 counties within the hospital catchment area, and overlapped with the distribution of all other recruited patients. Twenty-seven percent of the patients reported a recent tick-bite, most often on the arms and legs. Most patients had disease onset in July and August, which overlapped with the months of tick activity in central China.All the patients presented with non-specific febrile manifestations, including fever(96%), malaise(88%), myalgia(57%), cough(25%), and dizziness(14%). Only 2 patients had rash. Sixteen percent of 56 patients had eschar, 29% had lymphadenopathy, 100% had gastrointestinal symptoms, 34% had neurological symptoms, 43% had hemorrhagic manifestations, and 23% had signs of plasma leakage.Thrombocytopenia was observed in 70% patients, leucopenia in 59%, lymphopenia in 45%, elevated lactate dehydrogenase in 82%, aspartate aminotransferase in 70%, alanine transaminase in 54%, and creatinine kinase in 46%. In addition, 20% to 29% of the patients had elevated levels of gamma-glutamyl transpeptidase, blood urea nitrogen and total bilirubin and amylase.Eight patients died.The results of the kinetics of the laboratory parameters analyzed: The platelet counts were sharply decreased after disease onset, reached lowest level of 63.5×109/L around 10 days, and then gradually raised to normal. The leukocyte counts dropped dramatically after symptom onset, and attained the nadir level on day 6, with 28 patients developing leucopenia. The median leukocyte counts were never below the lower boundary. The serum levels of AST, ALT, and LDH, were elevated starting at 4 days, peaked at approximate 10 days after disease onset, and then restored slowly. The CK level was increased after disease onset, reached peak level about 10 days, then remarkably reduced to normal, and followed by a slight wave.The second part: Out of 733 participants, 19 infected with CRT, 405 infected with SFTS, and 37 with coinfection were identified. Both coinfection and SFTS groups had significantly longer duration of fever and more frequent lymphadenopathy, hemorrhagic signs, plasma leakage, thrombocytopenia, leukopenia, and elevated serum aspartate aminotransferase and creatine kinase than CRT infection group.Coinfection cases had even longer duration of fever, more frequent hemorrhagic signs and ascites than SFTS cases. The coinfection group had significantly more delayed recovery of platelet count and leukocyte count, as well as slower decline of viral load than SFTS group, after adjusting for sex, age, and interval from disease onset to admission. The coinfection increased fatal risk significantly with an odds ratio of 2.76.The third part:A total of 397 adult Haemaphysalis longicornis ticks were captured in the same regions as the patients resided. Thirty-three(8.3%) were positive for CRT, 37(9.3%) were positive for SFTSV, and 4(1.0%) were positive for both agents. The sequences of 434-bp 17-k Da antigen encoding gene from 29 samples were identical to those from the human patients(Gen Bank accession number KP769800), while the remaining 4 samples were identical to those from different human patients(Gen Bank accession number KP769801). For the sequences of 380-bp omp A gene, all 33 samples were identical to those obtained from the human patients(Gen Bank accession number KP769802). A total of 142 small mammals were captured in the same regions as the patients resided. Five(3.5%) were positive for CRT. The sequences of 434-bp 17-k Da antigen encoding gene from 5 samples were identical to those from the human patients(Gen Bank accession number KP769800). All samples were negative for SFTSV. CONCLUSIONIn conclusion, CRT infection was found in SFTS patients and should be included in the differential diagnosis of patients in the SFTS-endemic region. Not having rash and the high frequency of gastrointestinal syndromes could serve as the clinician to distinguish the disease from other SFGR. Neurologic and hemorrhagic manifestations may be important complications of CRT infection. Physicians should be aware of the possibility of infection with CRT to ensure molecular diagnosis and proper treatment with antibiotics. The public health significance of this emerging tick-borne pathogen warrants further investigation. SIENIFICANCE AND INNOVATIONThe clinical manifestations and laboratory findings of CRT infection were described. Patients coinfected with CRT and SFTS were firstly reported, and its clinical manifestations and laboratory indexes were compared which has a great contribute to public health. |
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