Infectious Medicine 2 (2023) 315–323

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Infectious Medicine
journal homepage: www.elsevier.com/locate/imj

Original Article

Chikungunya in Zhejiang Province, Southeast China

Jiangping Ren a,b,c, Feng Ling a,b,c, Ying Liu a, Jimin Sun a,b,c,∗
a
Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, China
b
Key Laboratory of Vaccine, Prevention and Control of Infectious Disease of Zhejiang Province, Hangzhou 310051, China
c Zhejiang Provincial Station of Emerging Infectious Disease Control and Prevention, Chinese Academy of Medical Sciences, Hangzhou 310051, China

a r t i c l e i n f o a b s t r a c t

Keywords: Background: Chikungunya is emerging and reemerging word-widely in the past decades. It is non-endemic in
Chikungunya Zhejiang Province, Southeast China. Aedes albopictus, one of major vectors of chikungunya, is widely-distribution
Imported cases in Zhejiang, and autochthonous transmission is possible after introducing chikungunya virus.
Epidemiological characteristics
Methods: Retrospectively collected the epidemiological, clinical and genetic data of chikungunya and conducted
the descriptive analysis and gene sequence analysis.
Results: From 2008 to 2022, 29 chikungunya cases, including 26 overseas imported and 3 local cases, were
reported and no cases died of chikungunya. More than half of the imported cases (53.85%) were from Southeast
Asia. Seasonal peak of the imported cases was noted between August and September, and 42.31% cases onset in
those 2 months. Eight prefecture-level cities and 16 counties reported cases during the study period, with Jinghua
(27.59%) and Hangzhou (24.14%) reporting the largest number of cases. The 3 local cases were all reported
in Qujiang, Quzhou in 2017. For imported cases, the male-female gender ratio was 2.71:1, 20–30 years old
cases (46.15%) and commercial service (42.31%) accounted for the highest proportion. Clinically, fever (100%),
fatigue (94.44%), arthralgia (79.17%), headache (71.43%) and erythra (65.22%) were the most common reported
symptoms. Eight whole-genome sequences were obtained and belonged to East/Central/South African (ECSA) or
Asian genotype.
Conclusions: With the change of immigration policy, the surveillance of chikungunya should be strengthened and
the ability of the case discovery and diagnosis should be improved in Zhejiang in the post-COVID-19 era.

1. Introduction It means “that which bends up” or “walking bent” in local

language, which references to the curved posture of pa-
Chikungunya fever is a mosquito-borne viral disease tients because of the severe joint pains. The virus respon-
caused by chikungunya virus (CHIKV). The major vectors sible for this disease was firstly isolated in 1957. Three
are Aedes aegypti and Aedes albopictus, which also transmit different CHIKV genotypes had been identified, named
dengue virus. CHIKV is a ∼11.8 kb long single-stranded, as East/Central/South African (ECSA), West African and
positive-sense RNA virus and belongs to the family To- Asian. In an outbreak with high epidemic magnitude in
gaviridae, genus Alphavirus. It contains 4 nonstructural coastal areas of Orissa, Eastern India, in 2010, the Indian
proteins, namely nsP1, nsP2, nsP3, and nsP4, encoded at Ocean Lineage (IOL) group within ECSA genotype was
the 5′ end of the genome, and 5 structural proteins en- isolated. The urban outbreak of CHIKV was first identi-
coded at the 3′ end of the genome, including 3 glyco- fied in Thailand in 1967, then in India in the 1970s. Af-
sylated proteins, namely E1, E2, E3, a small 64 amino- ter 2004, chikungunya outbreak accelerated its frequency
acids glycoprotein 6K, and one non-glycosylated nucleo- and expanded its geographical range. The first outbreak
capsid protein C (CP) [1]. Chikungunya was firstly used in European and the Americas was identified in 2007 and
to name a dengue-like disease with obvious joint pain in 2013, respectively. By now, CHIKV had been confirmed
Southern Tanganyika during later 1952 and early 1953. in over 110 countries in Asia, Africa, Europe and the

∗
Corresponding author.
E-mail address: [email protected] (J. Sun).

https://doi.org/10.1016/j.imj.2023.11.005
Received 1 August 2023; Received in revised form 4 October 2023; Accepted 13 November 2023
2772-431X/© 2023 The Authors. Published by Elsevier Ltd on behalf of Tsinghua University Press. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/)

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Americas, and always co-circulates with other ar- ported by Guangdong Province in 2010 [7]. Zhejiang is
boviruses, such as dengue virus, zika virus, and yellow one of the most densely populated and affluent province
fever virus. A meta-study conducted by Li et al. [2] in- in southeast of China. As the highly human mobility, Zhe-
dicated that the overall seroprevalence of CHIKV was jiang is vulnerabled to the traveled-related communicably
25% (95% CI: 22–29). Among all World Health Organi- disease. This study depicted the epidemiology and clini-
zation (WHO) regions, the rate was highest in the South- cal characteristics of chikungunya in Zhejiang province,
East Asian (42%, 95% CI: 17–67), lowest in the East- and tried to provide guiding information for the disease
ern Mediterranean Region (2%, 95% CI: 0–5). And the control and prevention in the post COVID-19 era.
top 5 countries/areas with highest infection rates were
Cameroon (68%, 95% CI: 25–100), Comoros (63%, 95% 2. Materials and methods
CI: 58–68), Haiti (58%, 95% CI: 56–59), Thailand (49%,
95% CI: 6–92), and Indonesia (39%, 95% CI: 32–45). 2.1. Study design and data collection
There were no significant differences in seroprevalences
between developed and developing countries, as well as This was a 15-year population-based surveillance study
between urban and rural areas. of chikungunya. All the cases would be recorded in the
Other than arthralgia, chikungunya is always indistin- National Notifiable Disease Surveillance System (NNDSS)
guishable with dengue in clinical. After infection, most after diagnosis by clinician. A survey, including demo-
people will recover in few days, some even have no no- graphic profile (name, age, gender, occupation and ad-
table symptoms and the estimated proportion of silent dress), epidemiological history and clinical presentation,
infection was 40%. But some will experience long-term would be conducted immediately by staff from the Center
disabilities, mainly arthralgia. A meta-analysis includ- for Disease Control and Prevention. Imported/indigenous
ing 24 studies indicated that the pooled prevalence rates cases were defined according to the epidemiological his-
for the long-term disabilities of CHIKV disease patients tory. Cases would be recognized as imported if he/she
were found 39.70% for follow up time between 6 and got infected in regions other than Zhejiang Province. The
12 months, 35.85% for follow up time between 12 and case that had no travel history in CHIKV-endemic region
18 months and 28.20% for greater than 18 months, re- or the region with autochthonous transmission of CHIKV
spectively [3]. Female, ≥40 years old, diabetes, hyper- in the past 12 days before the onset would be classified
tension, severity of pain at acute stage (self-assessment as the indigenous case. Chikungunya cases were diag-
numerically scale ≥ 7) were recognized as the risk factors nosed according to the diagnostic and treatment scheme
for the long-term disabilities. As an emerging arbovirus for chikungunya fever before August 2018 and diagno-
infection, chikungunya fever constitutes a serious pub- sis for chikungunya fever (WS/T 590-2018) after August
lic health problem. The study evaluated the global bur- 2018. The map of Zhejiang province was freely down-
den caused by CHIKV between 2010 and 2019 indicated loaded from National Earth System Science Data Sharing
that it caused the average yearly loss of over 106,000 Infrastructure (http://www.geodata.cn/). All the strains
disability-adjusted life years (DALYs) during this period with complete genome sequences of CHIKV were down-
[4]. Long-term rheumatic sequelae provided the largest load from the National Center for Biotechnology Informa-
DALY component, while acute symptoms and early death tion (NCBI; www.ncbi.nlm.nih.gov/). “Chikungunya” and
accounted for relatively less of the overall burden. CHIKV “Zhejiang” were used as keywords to get all the potential
caused substantially more burden in the Americas than in strains isolated in Zhejiang Province. The information of
any other region of WHO. It was believed that the dis- the strain, including date of isolation and the infectious
proportionate higher disease burden in the Americas was origin, was obtained through consulting the uploader
attributed to the limited active surveillance reporting in or the comment in NCBI. Basic Local Alignment Search
other regions and the lack of immunity in populations of Tool (BLAST; https://blast.ncbi.nlm.nih.gov/Blast.cgi)
the Americas. The economic burden study of the chikun- was used to identify the strains with highest similar-
gunya outbreak in the U.S. Virgin between 2014 and 2015 ity to that isolated in Zhejiang. Strains with complete
showed that the average number of missed day from work genome sequence and isolated from different locations,
in the 12 months following onset was 9 days, resulting time, of different genotypes were randomly downloaded
an estimated cost of $15.5 million; the estimated direct from NCBI.
healthcare costs for the first 2 months and 3–12 months
following the outbreak were $2.9 million and $0.6 mil- 2.2. Statistical analysis
lion, respectively; and the total estimated cost associated
with the outbreak ranged from $14.8 to $33.4 million (ap- WPS Office software was used for the data manage-
proximately 1% of gross domestic product) [5]. CHIKV is ment. SPSS17.0 software was employed for the statisti-
not endemic in mainland China, but since 2008, imported cal analysis. Quantitative data was presented as median
chikungunya cases were reported constantly [6]. The first and interquartile range (IQR). Qualitative data was de-
autochthonous transmission of CHIKV in China was re- scribed as percentage. ArcGIS (version 10.0.0) software
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was used for the geographical-distribution-plotting. Se- ported in 2017. A total of 3 indigenous cases were re-
quences were aligned with MAFFT 6.843 with L-INS- ported and all had onset in August. Other than Lishui,
i. A rectangular evolutionary tree was established with Shaoxing, and Taizhou, all the prefecture-level cities in
Maximum-likelihood method in MEGA 7.0.25. NC004162 Zhejiang reported chikungunya cases between 2008 and
was used as the reference sequence to identify the muta- 2022. Jinhua (27.59%) and Hangzhou (24.14%) were the
tion of amino acid in the E1–E3 gene. top 2 cities confirmed the most cases. Sixteen out of 91
counties reported case in this period and the total case
3. Results number ranged from 1 to 6 (Fig. 2). All the 3 indigenous
cases were reported in Qujiang. The 3 counties identified
3.1. Epidemiologic characteristic the most cases were Yiwu (6), Qujiang (4) and Tongxi-
ang (3). The male-female gender ratio for the imported
A total of 29 cases, including 26 imported and 3 in- case was 2.71:1. The age ranged from 20 to 74 years old,
digenous infections, were reported in Zhejiang during with median of 30 (26, 48.5) years old, and about half
2008–2022. No cases died of CHIKV. All the imported (46.15%) were at the age of 20–30 years old (Fig. 3).
cases were infected abroad, with 53.85% from South- More than one–third of imported cases (38.46%) were for-
east Asia, 38.46% from South Asia and 7.69% from sub- eigner. Business service (42.31%), Housework or unem-
Saharan Africa. Thailand (23.08%), Myanmar (19.23%), ployment (26.92%) were the most frequently reported oc-
Bangladesh (19.23%) and India (11.54%) were the top 4 cupations for imported cases. For the 3 indigenous cases,
countries exporting the most chikungunya cases to Zhe- 2 were female, the age were 22, 28, and 54 years old, re-
jiang in this period. The first ever recorded chikungunya spectively, and the occupation were worker, teacher and
case in Zhejiang was reported in 2008. Since then, cases farmer, respectively.
were reported with interval of several years. After 2016,
cases were confirmed every year between 2016 and 2020, 3.2. Clinical characteristic
with the annual case number peaked in 2019 (Fig. 1).
Yet, no cases were diagnosed in 2021 or 2022. More than The onset and confirmed date for all the cases were
three quarters of imported cases (88.46%) had onset be- available. The date of first visit to hospital was reported
tween April and September, and the seasonal peak was by 26 cases. The time intervals between onset and first
noted in August and September (Fig. 1). The first and visit ranged from 0 to 3 days, with the median of 1.00
the only autochthonous transmission of CHIKV was re- (0.00, 2.00) days. The intervals between first visit and
confirmation were at the range of 0 to 31 days and the
median was 0.00 (0.00, 2.00) days. The intervals between
onset and confirmation ranged from 0 to 82 days, and
the median was 2.00 (1.00, 4.50) days. Clinically, chikun-
gunya fever was characterized with fever (100%), fatigue
(94.44%), arthralgia (79.17%), headache (71.43%), and
erythra (65.22%) (Fig.4). For the 28 cases with fever, 25
cases reported the maximum body temperatures, and they
ranged from 38.2°C to 40°C, with 92% cases ≥38.5°C,
64% cases ≥39.0°C, and 62% cases ≥39.5°C. For the cases
with arthralgia, knee (73.33%) was most frequently in-
volved, followed by ankle (53.33%), wrist (46.67%) and
finger (35.71%). For the cases with erythra, rashes were
mostly on the extremities (75%), and the ratios that had
rashes on trunk and face were both 66.67%. For the cases
reporting their diagnosis on admission, more than half
(58.33%) were diagnosed as probable/confirmed chikun-
gunya fever, and one third were diagnosed as probable
dengue.

3.3. Phylogeny and amnion acid mutation of CHIKV

Eight strains isolated in Zhejiang with complete

genome sequence were obtained in PubMed, and 3 of
Fig. 1. The temporal distribution of chikungunya fever in Zhejiang province them were from indigenous cases (Fig. 5). The strain
during 2008–2022. of KC488650 was isolated from a Philippine seaman.

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Fig. 2. The geographical distribution of chikungunya fever in Zhejiang province during 2008–2022. (http://www.geodata.cn/data/datadetails.html?dataguid=
258898130861140&docid=6835).

It belonged to Asia genotype and had the highest sim- the first case of the outbreak. She had a business trip
ilarity with a strain isolated in the Philippines, 2012. in Bangladesh and got onset 4 days after returning
MT123008, MT123009, MT123010, and MG912993 were home. MG912993 had a similarity of 99.99% with the
isolated from the cases of the outbreak in Qujiang in 3 indigenous strains. And all the 4 strains (MT123008,
2017, and all the 4 sequences belonged to ESCA geno- MT123009, MT123010, and MG912993) had the high-
type. MT123008, MT123009, and MT123010 were from est similarity with MK468612 (99.95%–99.96%), which
the indigenous cases, and they were exactly the same was isolated from an infected in Bangladesh in July 2017.
in nucleotide sequence. MG912993 was isolated from OL840905, OL840906 and OL840907 were isolated in

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ruled out in order to reduce the risk of bleeding. Early

identification of severe cases that require hospitalization
is quite important. The keys of chikungunya prevention
and control in endemic region include reducing the num-
ber of mosquito-breeding habitats, killing mosquitoes and
avoiding mosquito bites. In general, the transmissions of
arboviruses include the sylvatic cycle (cyclical transmis-
sion between non-human animal host and insects) and
the urban cycle (cyclical transmission between human
and insects). Before 1990s, it was believed that CHIKV
was maintained in the sylvatic cycle in the jungle of Asia
Fig. 3. The age distribution of chikungunya fever in Zhejiang province during
2008–2022.
and Africa with occasional transmission into humans [8].
A series of large outbreaks, which started on the coast
of Kenya in 2004 and ravaged the Comoros Islands, the
island of La Réunion, and other islands in the south-
west Indian Ocean in early 2005, followed by an epi-
demic in the Indian subcontinent in 2005-2006, declare
the emergence and global expansion of CHIKV [9]. The
first ever autochthonous transmission of CHIKV in Eu-
ropean was identified in northeastern Italy in summer
2007, and at least 205 cases were reported. This is also
the first autochthonous CHIKV transmission in the tem-
perate region. The emergence of CHIKV in the Ameri-
cas was announced in December 2013, when the first
indigenous chikungunya cases was diagnosed in Saint
Martin. Since then, chikungunya had spread to 52 coun-
tries and territories in North, Central, and South Amer-
ica, and caused >3.47 million suspected and confirmed
cases and at least 544 deaths as 2022 [10–12]. The drivers
for the globally emergence and reemergence of CHIKV
were complicated: climate change, globalization which
Fig. 4. The clinical spectrum of chikungunya cases in Zhejiang province from favors travel and virus imported from CHIKV endemic re-
2008 to 2022. gion, virus evolution, urbanization, insufficient mosquito
control, vector adoption. Although transmission through
2019. OL840905 and OL840906 were from 2 cases with blood transfusions and vertical transmission had been
Thailand travel history, OL840907 was from a case with reported, the vast majority of cases were transmitted
Myanmar travel history. Those 3 strains all belonged to through female mosquito-biting. Aedes aegypti is the main
ESCA, and had high similarity in nucleotide sequence vector for CHIKV. Yet Aedes albopictus is an increasing im-
with each other (99.94%–99.99%). Besides that, they portant vector for CHIKV transmission as its role in the
were highly similarity with a strain from a newborn in- emergence of chikungunya in temperate areas, where no
fected in Yunan province in 2019 (MW110475, 99.95%– Aedes aegypti is founded. The geographical distribution of
99.96%) and an infected with Thailand travel history in Aedes aegypti in mainland China is limited, only in the bor-
Australia in 2019 (MN630017, 99.90%–99.93%). Com- der or coastal areas of Yunnan, Guangxi, Guangdong, and
pared with reference sequence of NC004162, all the 8 Hainan Province [13]. And the sustained vector surveil-
strains isolated in Zhejiang had amnion acid mutation lance indicated that its geographic distribution expended
(Table 1). in Yunnan Province but contracted in Guangxi, Guang-
dong, and Hainan Province in recent years. No Aedes ae-
4. Discussion gypti had been detected in Zhejiang. With the emergence
and reemergence of CHIKV, the first case in Zhejiang,
No specific antiviral treatment and commercial vaccine imported from Malaysia, was reported in 2008. Since
are available for chikungunya till now [8]. Several candi- then, chikungunya cases were identified on and off dur-
date vaccines are under research. The supportive treat- ing 2009–2015, and every year during 2016–2020. The
ment is mainly including analgesic and antipyretic ad- first autochthonous CHIKV transmission in Zhejiang was
ministration. Non-steroidal anti-inflammatory drugs, in- reported in Qujiang district, Quzhou city in 2017. One
cluding aspirin, should not be used until dengue can be case imported from Bangladesh and 3 indigenous cases

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Fig. 5. Phylogenetic tree of chikungunya strains based

on complete genome sequence.

were confirmed in this outbreak, and this is also the sec- ported chikungunya case in Spain, South America, Cen-
ond autochthonous transmission of CHIKV in mainland tral America and Caribbean were the 2 most frequently
China [14]. Two cases were reported in 2020, but no mentioned regions where they were infected [18]. The
cases were reported in 2021 and 2022. It was partly at- difference in the distribution of infection source might be
tributed to the control and prevention strategy conducted related to the differences in the preference of travel des-
during COVID-19 pandemic. For the imported cases in tination for the people in different region. A study con-
Zhejiang, Southeast Asia was the major source of infec- ducted in the United States indicated a statistically signif-
tion. And it was also the most frequently reported source icant positive association between passenger flows via air-
of infection for the imported cases in mainland China, line travel from countries experiencing chikungunya epi-
Japan and Prague, Czech Republic [7,15–17]. For the im- demics and the number of imported chikungunya cases at

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Table 1
The amnion acid mutation of strains isolated in Zhejiang, with NC004162 as reference.

GenBank Gene Segment Amnion acid mutation

KC488650 E1 72 N→S; 98 A→T; 145 T→A; 255 A→S; 269 V→M; 304 P→S
KC488650, MG912993, MT123008, MT123009, MT123010, E1 211 K→E
OL840905, OL840906, OL840907
MG912993, MT123008, MT123009, MT123010, OL840905, E1 284 D→E; 317I→V
OL840906, OL840907
KC488650 E2 2T→I; 5N→H; 118S→G; 146 Q→R; 149K→R; 157V→A;
205G→D; 248L→F; 255I→V;
317V→I; 318V→R; 371V→L; 375T→S; 384M→V
KC488650, MG912993, MT123008, MT123009, MT123010, E2 57G→K; 74I→M; 160N→T; 181L→M; 211I→T; 267M→R;
OL840905, OL840906, OL840907 299S→N; 344A→T
MG912993, MT123008, MT123009, MT123010, OL840905, E2 164A→T; 194S→G; 205G→S; 264V→A; 312T→M; 386V→A
OL840906, OL840907
KC488650, MG912993, MT123008, MT123009, MT123010, E3 23I→T
OL840905, OL840906, OL840907
KC488650 E3 33E→K; 44R→S; 60H→R

A, Alanine; C, Cysteine; D, Aspartic acid; E, Glutamic acid; F, Phenylalanine; G, Glycine; H, Histidine; I, Isoleucine; K, Lysine; L,
Leucine; M, Methionine; N, Asparagine; P, Proline; Q, Glutamine; R, Arginine; S, Serine; T, Threonine; V, Valine; W, Tryptophan; Y,
Tyrosine.

the state level. As the number of arriving airline passen- cross-reactivity among Flaviviruses need be attentioned.
gers increased by 10%, the estimated number of imported The ratio of asymptomatic infection for CHIKV (about
cases increased by 5.2% [19]. 30%) was lowest among those 3 viruses, and the ratio for
For imported chikungunya cases, male greatly outnum- zika and dengue were 80% and 60%–80%, respectively
bered female in Zhejiang, with the male-female gender ra- [24,25]. According to the review conducted by Jose Dario
tio of 2.71:1. But the surveillance conducted in Taiwan of Martinez [24], symptomatic CHIKV infection was charac-
China, Paris of France and Spain founded that there were teristic with high fever (≥39°C), arthritis and lymphocy-
significant more female in imported chikungunya cases, topenia, dengue could be differentiated with high fever
and the male-female gender ratio ranged from 0.41:1 to (≥39°C), neutropenia and thrombocytopenia, and symp-
0.55:1 [18,20,21]. For the imported cases in Japan and tomatic Zika virus infection was characteristic with mild
Iran, female was slightly more than male, and the gender fever and rash. Besides that, long-lasting, chronic articu-
ratios were 0.90:1 and 0.92:1, respectively [17,22]. More lar manifestations that may persist for months to years is
male cases were confirmed in Prague, Czech Republic a hallmark sign for chikungunya.
(gender ratio: 1.14:1) and mainland China (gender ratio: Virus evolution and importation of novel virus strain
1.54:1), while the gender ratio was still lower than that in are the important drivers for the emergence and reemer-
Zhejiang [7,16]. Research was needed to explore the po- gence of chikungunya [26]. IOL CHIKV, which carrying
tential reason for the overwhelming more male imported an alanine-to-valine mutation at position 226 within the
cases in Zhejiang. Besides that, the imported chikungunya E1 glycoprotein (E1-A226V), was responsible for a se-
case in Zhejiang were always reported as 20–50 years ries of outbreaks in Kenya, the Indian ocean, the Indian
old, business service/ housework or unemployment, and subcontinent and Southeast Asia in the previous decade
about half of the cases were 20–30 years old. Most of [26,27]. The adaptive mutation E1-A226V was proved
the cases would seek medical advice after onset. Clini- to enhance CHIKV replication in Aedes albopictus, which
cally, fever, fatigue, arthralgia, headache, erythra and fa- render the wide spread of CHIKV in the region abundant
cial blushing were the most frequently complained symp- with this mosquito. However, the IOL CHIKV of the out-
toms complained by the chikungunya case in Zhejiang. breaks during 2016–2020 in India, Pakistan, Bangladesh,
For the cases reporting their maximum body temperature, the Maldives, Myanmar, Thailand, and Kenya lacked E1-
more than 90% were ≥38.5°C, and about two thirds were A226V but carried a lysine to-glutamic acid mutation at
≥39°C. The study conducted in hospitalized febrile infants position 211 within the E1 glycoprotein (E1-K211E) and
younger than 3 months of age in French Guiana indicated a valine-to-alanine mutation at position 264 within the
that infants who presented irritability, high fever and skin E2 glycoprotein (E2-V264A). Further study suggested that
rash were more likely to have chikungunya infection [23]. the sub-lineage E1-K211E/E2-V264 was diverged from
Clinically, chikungunya is always undistinguished with ancestral IOLs in India around 2008, and caused spo-
dengue and zika virus disease, and one third of cases in radic outbreaks in India during 2010–2015 and in Kenya
Zhejiang were hospitalized as suspect dengue. For cases in 2016. After acquisition an isoleucine-to-valine muta-
with acute fever, rash, myalgia, or arthralgia and recent tion at position 317 within E1 (E1-I317V), it conducted
travel within the previous 2 weeks to an endemic area, the massive expansion in several regions during 2014–
all those 3 infections should be considered. Laboratory 2020, including the Indian subcontinent, Eastern Africa,
tests are particularly important for the diagnostic, but and Southeast Asia. The IOL CHIKV with double mutants

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of E1-K211E and E2-V264 had remarkably higher fitness and design, Investigation; Y.L., Data Curation, Investi-
for Aedes aegypti, as indicated by significant increase in gation; J.S., Conceptualization and design, Investigation,
virus infectivity, dissemination and transmission [28]. E1- Writing—review & editing.
I317 V possibly played a role in conferring competence to
Aedes albopictus [9]. Additional adaptive mutations that Acknowledgments
facilitate transmission by Aedes albopictus had been iden-
tified in E1 (A98T, K211E) and E2 (D60G, R198Q, G205S, We appreciate all the staff of hospital, Centers for Dis-
L210Q, I211T, K233E, K252Q) [8,9]. E1-A98T and E1- ease Control and Prevention in Zhejiang for their en-
K211E form a heterodimer within E1 on the surface of the deavor in disease surveillance, case diagnosis, reporting
viral particle and drive receptor interaction and entry. E2- and survey.
L210Q is responsible for increased CHIKV dissemination
in Aedes albopictus by increasing infectivity for epithelial Data available statement
cells lining the mosquito midgut [8,9]. The strain isolated
from the imported case in 2012, Zhejiang, is Asian geno- Research data are not shared.
type and has the mutants of E1-A98T, E1-K211E and E2-
I211T. All the 7 strains from cases in 2017 and 2019 be- Ethics statement
long to IOL group within ECSA genotype, and all have
no E1-A226V but with E1-K211E, E1-I317V, E2-G205S, Not applicable.
E2-I211T and E2- V264A.
Informed consent
5. Conclusion
Not applicable.
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