Introduction
Hemorrhagic
fever with renal syndrome (HFRS) is predominantly attributed to Hantaan
ortho-hantavirus (HTNV), a naturally occurring focal infectious disease
primarily transmitted through the inherent host of rodents. HTNV was
initially discovered in South Korea in 1978 and is prevalent in regions
in China, South Korea, Russia, and Vietnam[1, 2]. The endemic
strains in Northeast China encompass HTNV and Seoul virus (SEOV). Human
infection occurs via exposure to wild mice’s blood, saliva, urine, and
feces or through the transmission of vector organisms such as fleas
settling on the exterior of wild mice. It has been reported that there
were over 100,000 annual infection cases globally, with China being
among the most severely affected countries, accounting for more than
90% of these infections[3]. The recognizable HFRS course is divided
into five stages: fever, hypotensive shock, oliguria, polyuria, and
recovery[1]. These disease stages are well-defined in severe HFRS,
but the boundaries are not distinct or may overlap in mild and moderate
cases[4]. During the initial phase of the disease, there are
typically pronounced ”three pains”(headache, low back pain, orbital
pain) and ”three reds”(face red, neck red, and chest red), but it is
significantly relieved after the polyuria stage. Based on the severity
of fever, toxic symptoms, bleeding, shock, and kidney damage, the
clinical cases were divided into five categories: mild, moderate,
severe, critical, and atypical, with a mortality rate ranging from 0.5%
to 40%. The severity of the disease is also dependent on variants of
virulent agents[5]. HFRS can be instigated by Hantaan
ortho-hantavirus (HTNV), Seoul virus (SEOV), Dobrava-Belgrade virus
(DOBV), and Puumala virus (PUUV). HTNV and DOBV frequently infect and
cause severe HFRS, while SEOV mainly leads to moderate HFRS[1, 4].
Apart from clinical manifestations and epidemiological history,
diagnosis relies on laboratory testing methods and techniques such as
serology, polymerase chain reaction, immunochemistry, and virus
culture.
Severe
fever with thrombocytopenia syndrome bunyavirus (SFTSV) is an emergent
viral hemorrhagic fever with a significant fatality rate. It was
initially identified and documented in China in 2009 and was
subsequently isolated and named as severe fever with thrombocytopenia
syndrome (SFTS) in 2010, referred to as novel Bunyavirus[6]. It
belongs to the family Bunyaviridae and the genus Phlebovirus. SFTS
occurrences were primarily concentrated in East Asian countries such as
China, Japan, South Korea, and Vietnam. It has been reported that the
cumulative number of confirmed cases was 5360 in China by 2016, 866 in
South Korea by 2018, and 467 in Japan by 2019, respectively[7]. The
pathogen is predominantly transmitted through blood infection, and
tick-to-human transmission is the main route of human infection, with
Haemaphysalis longicornis being the most common transmission vector. The
infection manifests as severe fever, platelet and leukopenia, obvious
neurological symptoms, and gastrointestinal symptoms with high
mortality.
The
various hemorrhagic fevers (HFRS and SFTS) demonstrate similar epidemic
characteristics and clinical symptoms. Regarding epidemiological
characteristics, spatial and temporal distribution mirror the attributes
of susceptible populations. Meanwhile, the clinical characteristics are
similar in the early stage of the disease, such as general discomfort,
abrupt onset of fever, and irregular coagulation function[8].
Despite overlapping similarities in clinical features, instances of
co-infection with both viruses are extremely rare.
Liaoning
Province is recognized as a high-prevalence area for HFRS and SFTS,
exhibiting a recent upward trend. Additionally, the incidence rate of
SFTS persistently escalates, engendering significant public health
problems. The epidemic zones are mainly distributed in Dandong, Dalian,
Benxi, and other parts of Liaodong, particularly Fengcheng City and
Kuandian County, which are under the jurisdiction of Dandong. At the
same time, there exists considerable overlap between the endemic areas
and the vector dispersion. Liaoning Province harbors high tick density,
increasing the risk for humans and animals. Consequently, Liaoning
Province provides an ideal research environment for investigating
diseases.
It
is an important scientific question of effectively diagnosing viral
hemorrhagic fevers with similar characteristics. Presently, most studies
independently study analyze the clinical characteristics and diagnostic
methods of the two viral hemorrhagic fevers in isolation or establish
diagnostic models rooted in clinical prediction and identification,
failing to comprehensively combine clinical data and specimens for a
thorough analysis of the correlation between the two viral hemorrhagic
fevers. Besides, some research on HFRS mainly consist of descriptive
studies on case reports, nursing experience, and clinical
characteristics, with minimal studies on severe HFRS[9, 10].
Therefore, utilizing clinical data and combining it with the detection
of patient samples, this study conducted the statistical analysis of
severe cases of HFRS and explored the relationship between co-infection
and disease severity combined with laboratory detection.
The
present study collected the clinical case information and blood
specimens of 22 patients clinically diagnosed with HFRS admitted to
Dandong Infectious Diseases Hospital of Liaoning Province from December
2021 to October 2022 in Northeast China, where two types of infectious
diseases are highly endemic. These cases were categorized into severe
and non-severe groups. Statistical description and inference were
applied to compare and analyze the clinical characteristic differences
between the two groups. Meanwhile, molecular biological detection of
common vector infectious disease pathogens was carried out on the blood
samples of patients, molecular biological detection of their cell
cultures was carried out, and the pathogens were isolated. The severity
of HFRS was identified under different factors. Moreover, the
co-infection of HFRS and SFTS was also discussed to provide scientific
reference for the early and timely differential diagnosis, effective
prevention, and treatment of severe cases.