4 Discussion
Tick-borne diseases are the main cause of vector-borne diseases and have
broad global distribution. They are mainly natural epidemic diseases,
most common in forests, bushes, and semi-desert grasslands(Wu, Na, Wei,
Zhu, & Peng, 2013). There are at least 7 genera and 104 species of
ticks in China. Northeast China has a mountainous terrain, has abundant
biological resources, has geographical complexity, and has high species
diversity, which provide an ecological and biological basis for the
survival and reproduction of ticks. In this study, we found that the
ticks distributed in the forest area of Northeast China are dominated
by the long-horned blood ticks. Most patients affected by SFTS live in
mountainous, hilly, or dense jungle areas and have a history of working
outdoors. More than 80% of the cases are farmers, and there is history
of field work, livestock contact, etc., and a few patients have history
of tick bites. Among all the 17 suspected SFTS patients in this study,
all cases occurred from the end of March to the end of June, and 94% of
the cases (16/17) were from Changbai Mountain and other mountainous
areas, forests, and hills in Northeast China, It is highly consistent
with the active season and regional distribution of ticks in Liaoning
Province.
SFTSV strains have been isolated from ticks in South Korea, Japan, and
other regions sharing borders with or adjacent to China(Park et al.,
2014; Yasukawa, 2008; Yun et al., 2015). Reports from the East Asian
region show that the average mortality rate of SFTSV varies greatly,
from 5.3% to 16.2% in China, 20% in Japan, and 23.3% in South Korea.
Among the six known A-F genotypes of SFTSV(Fu et al., 2016), genotype B
has the highest morbidity and mortality rates, which are significantly
higher than those of the other genotypes. The incidence of the F
genotype is lower than that of the B genotype, but its mortality rate is
also higher, while the A genotype has the lowest mortality rate(Yun et
al., 2020). The most common genotypes in China are genotypes A, D, and
F, and the mortality rate is relatively low, while the most common
genotype in Japan and South Korea is B. Therefore, a comparison of viral
genotypes and mortality indicates that the differences in reported case
mortality may be related to the differences in the distribution of SFTSV
genotypes in different countries. The number of clinical cases infected
with certain SFTSV genotypes
(especially reassortant genotypes) is small, which prevents the
determination of the association between genotype and case mortality.
There is currently no vaccine or specific antiviral drug for SFTSV.
Ribavirin is considered to be a potential antiviral drug for SFTS, but
several retrospective studies have shown that ribavirin has not been
effective in improving disease prognosis (Li et al., 2018; Liu et al.,
2013). (Li et al., 2019) found that benidipine hydrochloride (a calcium
channel blocker, CCB) can inhibit SFTSV infection by interfering with
virus internalization and reducing viral genome replication. Further
experiments showed that a large number of CCBs including nifedipine
inhibited SFTSV infection as well, indicating that CCB therapy may be
developed as an effective strategy for the treatment of SFTSV infection.
Our previous research showed that among the various pathogens carried by
ticks distributed in the Changbai Mountain forest area in China, theRickettsia positivity rate was the highest, and it was close to
10% in some areas (Qi et al., 2014). TheRickettsia detected in this
study is consistent with the newly discovered ”DandongRickettsia ” genotype in 2018 and has is genetically close toRickettsia Heilongjiang. This genotype belongs to the class
Alphaproteobacteria, order Rickettsiales, in the spotted fever group
rickettsiae of the genus Rickettsia .
The disease caused byRickettsia in Heilongjiang is called the ”Far-East tick-borne
Spotted Fever” (FESF) , FESF has been considered as an important
emerging infectious disease in Northeast Asia for this rickettsiosis has
been diagnosed in Northeast of China, east-Siberian and far-eastern
regions of Russia, and Japan. Rickettsia infection usually
manifests as fever, headache, and rash, as well as muscle pain and
arthralgia. The typical symptom is eschar-like skin lesions formed by
the bite of a tick or mite, and the mortality rate is low under
reasonable treatment. However,
rashes and eschar did not appear in the 17 patients in this study, which
may be because the skin lesions were hidden and painless, making them
difficult to observe and easy to ignore. The diagnosis of rickettsial
diseases can be achieved by RT-PCR or conventional PCR detection in
diseased tissues (Denison, Amin, Nicholson, & Paddock, 2014). However,
sampling errors may cause false negatives, and patients with
insignificant skin lesions may be completely ignored. Due to similar
clinical manifestations caused by different rickettsial infections,
there are cross-reactions in serological methods. Pathogen culture is
difficult, and the application of molecular techniques in whole blood
are limited so far. Thus, rapid and reliable molecular blood detection
of rickettsial diseases are still difficult to achieve. Indirect
immunofluorescence assay is considered to be the gold standard, but due
to its extensive cross-reactivity, this method has limited use in the
determination of species within serogroups (Paris & Dumler, 2016).
In our study, based on epidemiological data, clinical symptoms, and
routine blood tests, 17 patients were initially classified as suspected
SFTS patients. After molecular diagnostic testing, 5 SFTS patients were
confirmed to have SFTSV. To understand whether there is a mixed
infection of sftsv and rickettsia in patients bitten by ticks,
From the 17 patient blood samples,
7 samples were chosen for Rickettsia -specific IgG antibody
testing, and the positivity rate was 100%. Of these 7 samples, 3
samples were from patients diagnosed with SFTS and 4 samples were from
SFTS negative patients. Considering that ticks carry SFTSV and
”Dandong-type Rickettsia ”, we conclude that tick-borne SFTSV and
”Dandong-type Rickettsia ” infections are endemic in forest areas
in Northeast China are more common. We hypothesize that
SFTSV-”Dandong-type Rickettsia” coinfection complicates patient
conditions. Therefore, we believe that in diagnosing tick-borne diseases
such as SFTSV, tick-borne encephalitis, and renal hemorrhagic fever
syndrome, co-infection with Rickettsia will have to be
considered. SFTS and other related tick-borne diseases should also be
screened for patients with rickettsial infection.