A total of 49 patients with hemorrhagic fever caused by HYSV were included; 8 (16.3%) patients died. A fatal outcome was associated with high viral RNA load in blood at admission, as well as higher serum liver transaminase levels, more pronounced coagulation disturbances (activated partial thromboplastin time, thrombin time), and higher levels of acute phase proteins (phospholipase A, fibrinogen, hepcidin), cytokines (interleukin [IL]-6, IL-10, interferon-γ), and chemokines (IL-8, monocyte chemotactic protein 1, macrophage inflammatory protein 1b). The levels of these host parameters correlated with viral RNA levels. Blood viral RNA levels gradually declined over 3-4 weeks after illness onset, accompanied by resolution of symptoms and laboratory abnormalities. Viral RNA was also detectable in throat, urine, and fecal specimens of a substantial proportion of patients, including all fatal cases assayed. CONCLUSIONS. Viral replication and host immune responses play an important role in determining the severity and clinical outcome in patients with infection by HYSV.
Surveys were carried out to better understand the tick vector ecology and genetic diversity of Huaiyangshan virus (HYSV) in both regions of endemicity and regions of nonendemicity. Haemaphysalis longicornis ticks were dominant in regions of endemicity, while Rhipicephalus microplus is more abundant in regions of nonendemicity. HYSV RNA was found in human and both tick species, with greater prevalence in H. longicornis and lesser prevalence in R. microplus. Phylogenetic analyses indicate that HYSV is a novel species of the genus Phlebovirus. Recently, a hemorrhagic fever-like disease caused by a novel bunyavirus occurred in China (14, 16). Yu et al. reported the disease as severe fever with thrombocytopenia syndrome (SFTS) (14). As thrombocytopenia is not specific for this disease and is present in nearly all hemorrhagic fevers caused by viruses (11) or Rickettsia (15), we previously proposed naming the syndrome Huaiyangshan hemorrhagic fever (HYSHF) and the virus Huaiyangshan virus (HYSV) (16). Haemaphysalis longicornis ticks might be the vector of HYSV (14, 16). However, less is known about the arthropod vector ecology, the genetic diversity, and the phylogeny of HYSV. Thus, we performed an investigation in regions of endemicity and nonendemicity in Henan and Hubei provinces ( Fig. 1).A total of 17,731 adult ticks were collected (Table 1). After morphological examination and sequence analysis of mitochondrial 12S ribosomal DNA (rDNA) as described previously (2, 16), only H. longicornis and Rhipicephalus microplus were found. In the regions of endemicity, 4,501 ticks (3,498 H. longicornis and 1,003 R. microplus) were collected from 15 counties of Henan and Hubei. In the regions of nonendemicity, 13,230 ticks (400 H. longicornis and 12,830 R. microplus) were collected from 23 counties of Hubei. These data suggested that H. longicornis and R. microplus were the dominant species in regions of endemicity and regions of nonendemicity, respectively.All ticks were grouped into 1,180 pools (450 pools from a region of endemicity and 730 pools from a region of nonendemicity) according to species, host, and geographic origin. H. longicornis and R. microplus represented 365 (30.93%) and 815 (69.07%) pools, respectively. For screening HYSV and sequencing the partial S segment (nucleotides [nt] 63 to 663) or L segment (nt 2208 to 3121) and whole-genome sequences of HYSV, total RNA was extracted from ticks and human sera and was then subjected to reverse transcription-PCR (RT-PCR) as described previously (16). As a result, HYSV RNA was identified in 18 (4.93%) H. longicornis pools and in 5 (0.613%) R. microplus pools, suggesting that both species can carry HYSV. Remarkably, the HYSV RNA-positive H. longicornis ticks were found only in the regions of endemicity, whereas HYSV RNA was identified in R. microplus ticks from both the regions of endemicity (2 pools) and neighboring regions of nonendemicity (3 pools) (Fig. 1). Obviously, the prevalence of HYSV was higher in H. longicornis ticks than in R. microplus ticks and higher in...
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