Abstract
Chikungunya fever, an acute infectious disease caused by Chikungunya virus (CHIKV), is transmitted by Aedes aegypti mosquitoes, with fever, rash, and joint pain as the main features. 1952, the first outbreak of Chikungunya fever was in Tanzania, Africa, and the virus was isolated in 1953. The epidemic has expanded from Africa to South Asia, the Indian Ocean islands and the Americas, and is now present in more than 100 countries and territories worldwide, causing approximately 1 million infections worldwide each year. In addition, fatal cases have been reported, making CHIKV a relevant public health disease. The evolution of the virus, globalization, and climate change may have contributed to the spread of CHIKV. 2005–2006 saw the most severe outbreak on Reunion Island, affecting nearly 35% of the population. Since 2005, cases of Chikungunya fever have spread mainly in tropical and subtropical regions, eventually reaching the Americas through the Caribbean island. Today, CHIKV is widely spread worldwide and is a global public health problem. In addition, the lack of a preventive vaccine and approved antiviral treatment makes CHIKV a major global health threat. In this review, we discuss the current knowledge on the pathogenesis of CHIKV, focusing on the atypical disease manifestations. We also provide an updated review of the current development of CHIKV vaccines. Overall, these aspects represent some of the most recent advances in our understanding of CHIKV pathogenesis and also provide important insights into the current development of CHIKV and potential CHIKV vaccines for current development and clinical trials.
1. Introduction
Chikungunya virus (CHIKV) is a single positive-standard RNA virus in the alphavirus genus of the family of Togaviridae (). The genome is about 11.8kb in length, including the 5′ -terminal non-coding region (5′ UTR), two independent open reading frames (ORF), 1 poly A tail and 3′ UTR, encoding four non-structural proteins (nsP1, nsP2, nsP3, nsP4) and six structural proteins (capsid protein C, envelope protein E3, E2,6K, E1, and TF). The genes encoding the viral envelope proteins have been mutated in recent decades, which facilitated CHIKV transmission by Aedes albopictus (). CHIKV has four genotypes: East-Central-South African genotype (ECSA), West African genotype, Asian genotype and Indian OceanLineage genotype (IOL). Among them, the Asian and Indian Ocean Lineage genotypes were derived from ECSA. The ECSA and Asian genotypes are mainly transmitted by Aedes aegypti, and the Indian Ocean genotype has acquired the ability (, ) to transmit through Aedes albopictus after genetic mutations occur. CHIKV can be inactivated by 70% ethanol, l% sodium hypochlorite, 2% glutaraldehyde, and lipid solvents, peracetic acid, and other disinfectants. CHIKV is relatively stable at minus 40 degrees, and it can be inert by heating to above 58 degrees. Although CHIKV infection is usually a self-limiting disease, some patients develop persistent joint pain after the acute phase that may last for months or years (, ).
2. Epidemiology
2.1. Source of infection
In the urban epidemic source sites, patients and hidden infected persons are the main sources of infection, and their transmission mode is mainly human-mosquito-human. In the early stage of the disease, 2–5 d can produce a high titer of viremia, which is very infectious. In the jungle epidemic foci, infected monkeys, orangutans, baboons and other primates, and wild animals are the main sources of infection of the disease, and the mode of transmission is mainly primate-mosquito-primate ().
2.2. Route of transmission
Aedes, including Aedes albopictus mosquitoes, Aedes aegypti mosquitos, and African Aedes mosquitoes, are the primary vectors of CHIKV, Aedes albopictus originated in Asia and is a wild mosquito species distributed in tropical, subtropical, and temperate rural and urban areas, and is currently distributed globally. Its eggs are drought tolerant and, therefore resilient, and have surpassed Aedes aegypti as the main local mosquito species in many areas. Aedes aegypti is a domestic mosquito species widely distributed in tropical and subtropical cities and suburbs. It mainly breeds from the water in small containers in residential areas. Aedes africanus is an African wild mosquito species, addicted to primate blood and spreads viruses in wild animals, playing a major role in virus circulation in jungle-type foci (, ).
2.3. Susceptibility and immunity
The population is generally susceptible to CHIKV and can develop at any age. After infection, dominant infection and recessive infection, the latter majority, and both can obtain immunity.
2.4. Epidemiological characteristics
2.4.1. Regional distribution
Since the first CHIKV infection case was reported in Africa in the 1950s, subsequent epidemics mainly outbreak in the sub-Saharan region of Africa, Southeast Asia, South Asia, the Indian Ocean islands, and the Western Pacific region. In 2007, the first European case was reported in Italy. In late 2013, the first local transmission case was confirmed in the Americas, demonstrating that mosquitos in these areas also got infected with CHIKV and spread to humans. In 2022, over 250 thousand autochthonous suspected and confirmed cases have been reported in the Americas. The cross-regional prevalence of epidemics indicated vectors adapted to more temperate regions in Europe and America.
2.4.2. Population distribution
The population distribution of Chinkungunya infection for native and imported cases is different. All genders and age groups are highly susceptible to infection before Chikungunya fever becomes an endemic disease. When indigenous transmission occurs, patients at the extreme age spectrum are to some extent more susceptible and at higher risk to developed severe symptoms.
Seasonal prevalence is consistent with the breeding season of the vector mosquitoes. Popular seasons mainly concentrated on the rainy season with high temperature and high humidity. In subtropical and temperate regions, summer and autumn are the popular seasons. In Asia, the first case of CHIKV was reported in Cambodia in 1961, probably with () caused by an Asian genotype circulating in the region at the time. Forty years later, Chikungunya fever outbreak again in Sri Lanka in 2007, causing more than 37,000 infected cases (). The intensification and expansion of vector-borne diseases may be a major threat to climate change. In fact, despite many other complex factors (such as mosquito-range constraints and virus evolution), climate change will cause increased (, ) exposure to Aedes-borne viruses.
3. Pathogenesis
CHIKV belongs to the “New World” group of alphaviruses, which mainly cause musculoskeletal inflammatory diseases such as arthralgia, arthritis, and myalgia, classified as “arthritis virus”, including Chikunonia, Ross River virus (RRV), Ballmach Forest virus (BFV), Group Sindbis and Mayaro (Mayv) (, ). CHIKV infects multiple cell types, including dendritic cells, and macrophages. Synovial fibroblasts, endothelial cells, and myocytes. In the human body, osteoblasts can also be infected, causing arthropathy and erosive disease () in patients with chronic arthritis.
On the viral surface, the heterodi-and trimers of the structural proteins E1 and E2 proteins form “viral spikes”, and the glycoprotein E2 is responsible for binding to the receptor, while E1 is responsible for the fusion of () to the membrane. Given that CHIKV infects multiple types of cells, the cellular proteins that interact with the virus are also diverse in (). Mammalian cell receptors known for CHIKV include prohibition (PHB), TIM-1, MXRA8, CD147, lectin DC-SIGN, and ATP synthase subunit and FHL1 (–). Furthermore, other phosphatidylserine-binding proteins, such as Axl, TIM-4 and TIM-1, have also been shown to promote (–) in CHIKV-infected cells. Otherwise, autophagy apoptosis is an important infection mechanism. It has been shown that CHIKV initiates apoptosis through both endophytic and exogenous pathways in HeLa cells, as well as in primary fibroblasts. By hiding within these apoptotic bleeding sites, CHIKV is able to infect adjacent cells. These infectious foci infect macrophages like Trojan viruses, and interestingly, the replication process of this cell-infected virus in macrophages does not produce a proinflammatory response, constituting the mechanism (), by which CHIKV invades the host cell and escapes the host response. After infection, the incubation period is 3–7 days, in the acute phase, and the most common symptoms are high fever, stiffness, headache, photophobia and ecchymosis rash or punctate rash. Similar to other arboviruses, DENV and ZIKV, the peak of viremia in CHIKV-infected people matched the duration of fever for (–), and hospitalized cases had higher viremia than those that did not require hospitalization. Roughly estimated, 30–40% of infected individuals experience some long-term sequelae, including persistent arthralgia and / or arthritis, with about 37% having severe persistent arthralgia. Some studies show that patients older than 40 years, of the female gender, with higher levels of CXCL8, detected in the acute phase of the disease have been shown to associate (35–37) with persistent arthralgia in CHIK. CHIKV susceptibility and in vitro single-cell correlation studies showed that the arthritis-related genes RANTES / CCL5 and IL-8 significantly upregulate (38) in infected human synovial fibroblasts. Following viral replication in vivo, the cells target muscle, joints, and skin fibroblasts, and these tissue cell damage was also observed in human biopsy samples. A study of neonatal and adult mouse models with IFN knockout found that the severity of CHIKV infection was (39) associated with the IFN- / R signaling pathway.
4. Vaccines and treatment
Despite the prevalence of CHIKV in many regions, no marketed vaccine is available. Treatment of CHIKV-infected patients mainly provides symptom relief through the use of anti-inflammatory drugs, such as methotrexate, sulfasalazine, leflunomide, and hydroxychloroquine, which has been utilized but with limited efficacy (40, 41). A wide range of CHIKV vaccine candidates under preclinical development, including whole-virus inactivated vaccine (42, 43), VEE / CHIKV chimeric vaccine, recombinant adenovirus vector vaccine, DNA-and mRNA-based CHIKV vaccine, and the live attenuated vaccine (44–50) with stronger and longer immune response, are currently in clinical research phase I-III, and we need to focus on the antibody dependence (ADE) phenomenon (51), with a breakthrough in future vaccine development.
5. Outlook
CHIKV is spreading rapidly in many countries, and the vaccination of susceptible people is the most effective way to control the infection, and we can expect a CHIKV vaccine to be available to the general public in perhaps 5–10 years. Before vaccines and specific drugs are put on sale, we still need to strengthen CHIKV testing for suspected acute neurological symptoms and conduct timely detection of cases and treatment of patients to contain the spread of the epidemic.
Statements
Author contributions
YT, LC, and XinH: conceptualization. XibH and XinH: methodology. HL and HT: resources. YT and XinH: writing-original draft preparation. LC: writing-review and editing. LW: visualization. XibH: supervision. SL: project administration. YT: funding acquisition. All authors contributed to the article and approved the submitted version.
Funding
This study was supported by the National Natural Science Foundation of China (92169117), the Hubei Youth Talent program (2021), the Hubei Public Health Youth Talent program (2021), the Hubei Medical Youth Reserve Talent program (2019), and the Hubei Young Talent Plan (2017) as well as Hubei Outstanding Young Funding Program (2020CFA075).
Acknowledgments
We thank to all participants of this study and Katherine A. Mason for her help in the language of the manuscript.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1.
LumsdenWHR. An epidemic of virus disease in Southern Province, Tanganyika territory, in 1952–1953 II. General description and epidemiology. Transactions of the Royal Society of Tropical Medicine and Hygiene. (1955) 49:33–57. 10.1016/0035-9203(55)90081-X
2.
KucharzEJCebula-ByrskaI. Chikungunya fever. Eur J Intern Med. (2012) 23:325–9. 10.1016/j.ejim.2012.01.009
3.
Leparc-GoffartINougairedeACassadouSet al. Chikungunya in the Americas. Lancet. (2014) 383:514. 10.1016/S0140-6736(14)60185-9
4.
SuhrbierAJaffar-Bandjee MCGasqueP. Arthritogenic alphaviruses—an overview. Nat Rev Rheumatol. (2012) 8:420–9. 10.1038/nrrheum.2012.64
5.
KamalMKenawyMARadyMHKhaledASSamyAM. Mapping the global potential distributions of two arboviral vectors Aedes aegypti and Ae. albopictus under changing climate. PloS ONE. (2018) 13:e0210122. 10.1371/journal.pone.0210122
6.
EconomopoulouADominguezMHelynckBSissokoDWichmannOQuenelPet al. Atypical Chikungunya virus infections: clinical manifestations, mortality and risk factors for severe disease during the 2005–2006 outbreak on Reunion. Epidemiol Inf. (2009) 137:534–41. 10.1017/S0950268808001167
7.
HoarauJ-JBandjeeM-CJTrototPKDasTLi-Pat-YuenGDassaBet al. Persistent chronic inflammation and infection by Chikungunya arthritogenic alphavirus in spite of a robust host immune response. J Immunol. (2010) 184:5914–27. 10.4049/jimmunol.0900255
8.
BurtFJChenWMinerJJLenschowDJMeritsASchnettlerEet al. Chikungunya virus: an update on the biology and pathogenesis of this emerging pathogen. Lancet Infect Dis. (2017) 17:e107–17. 10.1016/S1473-3099(16)30385-1
9.
HaeseNNBroeckelRMHawmanDWHeiseMTMorrisonTEStreblowDN. Animal models of Chikungunya virus infection and disease. J Inf Dis. (2016) 214: S482–S487. 10.1093/infdis/jiw284
10.
EscobarMNietoAJLoaiza-OsorioSBaronaJSRossoF. Pregnant women hospitalized with chikungunya virus infection, Colombia, 2015. Emerg Infect Dis. (2017) 23:1777. 10.3201/eid2311.170480
11.
TandaleBVSathePSArankalleVAWadiaRSKulkarniRShahSVet al. Systemic involvements and fatalities during Chikungunya epidemic in India, 2006. J Clini Virol. (2009) 46:145–9. 10.1016/j.jcv.2009.06.027
12.
KumarVJainRKumarANischalNJorwalPSonejaMet al. Chikungunya fever presenting as life threatening thrombotic thrombocytopenic purpura. J Assoc Physicians India. (2017) 65:96–100.
13.
EpelboinLBidaudBMosnierETurnierPLVesinGWalterGet al. Fatal case of chikungunya and concomitant thrombotic thrombocytopenic purpura in French Guiana during air flight medical evacuation. J Travel Med. (2017) 24:tax028. 10.1093/jtm/tax028
14.
HamidADhroliaMFQureshiRImtiazSAhmadA. Acute kidney injury secondary to rhabdomyolysis: a rare presentation of chikungunya fever. J Coll Physicians Surg Pak. (2018) 28:S94–S94. 10.29271/jcpsp.2018.06.S94
15.
ChungSJChlebickiMP. A case of Addisonian crisis, acute renal failure, vesiculobullous rash, rhabdomyolysis, neurological disturbances and prolonged viraemia in a patient on long term steroids. J Clin Virol. (2013) 57:187–90. 10.1016/j.jcv.2013.01.004
16.
ZimMAMSamI-COmarSFSChanYFAbuBakarSKamarulzamanA. Chikungunya infection in Malaysia: comparison with dengue infection in adults and predictors of persistent arthralgia. J Clin Viro. (2013) 56:141–5. 10.1016/j.jcv.2012.10.019
17.
SolankiBSAryaSCMaheshwariP. Chikungunya disease with nephritic presentation. Int J Clin Pract. (2007) 61:1941–1941. 10.1111/j.1742-1241.2007.01329.x
18.
MahendradasPRangannaSKShettyRBaluRNarayanaKMBabuRBet al. Ocular manifestations associated with chikungunya. Ophthalmology. (2008) 115:287–91. 10.1016/j.ophtha.2007.03.085
19.
HozJMdBayonaBViloriaSAcciniJLJuan-VergaraHSViasusD. Fatal cases of Chikungunya virus infection in Colombia: diagnostic and treatment challenges. J Clin Viro. (2015) 69:27–9. 10.1016/j.jcv.2015.05.021
20.
TorresJRLCGCastroJSRodríguezLSaraviaVArvelaezJet al. Chikungunya fever: atypical and lethal cases in the Western hemisphere: a Venezuelan experience. IDCases. (2015) 2:6–10. 10.1016/j.idcr.2014.12.002
21.
MercadoMAcosta-ReyesJParraEGuzmánLBeltránMGasquePet al. Renal involvement in fatal cases of chikungunya virus infection. J Clin Viro. (2018) 103:16–8. 10.1016/j.jcv.2018.03.009
22.
CostaDMdNGouveiaPAdSilvaGEdNevesPDMdVajgelGCavalcanteMAGdet al. The relationship between chikungunya virus and the kidneys: a scoping review. Rev Med Virol. (2022) e2357. 10.1002/rmv.2357. [Epub ahead of print].
23.
SharpTMKeatingMKShiehW-JBhatnagarJBollwegBCLevineRet al. Clinical characteristics, histopathology, and tissue immunolocalization of chikungunya virus antigen in fatal cases. Clin Infect Dis. (2021) 73:e345–54. 10.1093/cid/ciaa837
24.
AuroreA-CCoudercTDueymesJ-MDelignyCLecuitMMoliniéVet al. The clinicopathological spectrum of kidney lesions in Chikungunya fever: a report of 5 cases with kidney biopsy. Am J Kidney Dis. (2021) 78:902–6. 10.1053/j.ajkd.2021.04.012
25.
CostaDMdNMachadoCENevesPDBritoDJOiSBarrosFHet al. Chikungunya virus as a trigger for different renal disorders: an exploratory study. J Nephrol. (2022) 35:1437–47. 10.1007/s40620-022-01256-6
26.
BetancurJ-FNavarroEPBonillaJHBCortésADVélezJDEcheverryAet al. Catastrophic antiphospholipid syndrome triggered by fulminant chikungunya infection in a patient with systemic lupus erythematosus. Arthritis Rheumatol (Hoboken, NJ). (2016) 68:1044. 10.1002/art.39580
27.
Coelho JúniorJLIsraelKCPMachadoCEEMunizMPRGattoGCBarrosFHSet al. Thrombotic microangiopathy associated with arboviral infection: Report of 3 cases. PLoS Negl Trop Dis. (2021) 15:e0009790. 10.1371/journal.pntd.0009790
28.
FreitasARRDonalisioMRAlarcón-ElbalPM. Excess mortality and causes associated with chikungunya, Puerto Rico, 2014–2015. Emerg Infect Dis. (2018) 24:2352. 10.3201/eid2412.170639
29.
FrutuosoLCVFreitasARRCavalcantiLPdDuarteEC. Estimated mortality rate and leading causes of death among individuals with chikungunya in 2016 and 2017 in Brazil. Rev Soc Bras Med Trop. (2020) 53.:e20190580 10.1590/0037-8682-0580-2019
30.
GuptaAJunejaDSinghOGargSKAroraVDeepakD. Clinical profile, intensive care unit course, and outcome of patients admitted in intensive care unit with chikungunya. Indian J Crit Care Med. (2018) 22:5. 10.4103/ijccm.IJCCM_336_17
31.
GodaertLBartholetSDorléansFNajioullahFColasSFanonJ-Let al. Prognostic factors of inhospital death in elderly patients: a time-to-event analysis of a cohort study in Martinique (French West Indies). BMJ Open. (2018) 8:e018838. 10.1136/bmjopen-2017-018838
32.
Kee A CLYangSTambyahP. Atypical chikungunya virus infections in immunocompromised patients. Emerg Infect Dis. (2010) 16:1038. 10.3201/eid1606.091115
33.
JuniorGBdPintoJRMotaRMSNetoRdPDaherED. Impact of chronic kidney disease on chikungunya virus infection clinical manifestations and outcome: highlights during an outbreak in northeastern Brazil. Am J Trop Med Hyg. (2018) 99:1327. 10.4269/ajtmh.18-0531
34.
PintoJRJuniorGBdMotaRMSMartinsPSantosAKTde MouraDCNet al. Clinical profile and factors associated with hospitalization during a Chikungunya epidemic in Ceará, Brazil. Rev Soc Bras Med Trop. (2019) 52:e20190167. 10.1590/0037-8682-0167-2019
35.
JuniorGBdPintoJRMotaRMSNetoRdPDaherED. Risk factors for death among patients with Chikungunya virus infection during the outbreak in northeast Brazil, 2016–2017. Trans R Soc Trop Med Hyg. (2019) 113:221–6. 10.1093/trstmh/try127
36.
SimiãoARBarretoFKAOliveiraRMABOliveraRCavalcanteJNetoAet al. A major chikungunya epidemic with high mortality in northeastern Brazil. Rev Soc Bras Med Trop. (2019) 52.:e20190266 10.1590/0037-8682-0266-2019
37.
GasperinaDDBalsamoMLGaravagliaSDRovidaFBaldantiFGrossiPA. Chikungunya infection in a human immunodeficiency virus-infected kidney transplant recipient returning to Italy from the Dominican Republic. Transpl Infect Dis. (2015) 17:876–9. 10.1111/tid.12453
38.
GirãoESDos SantosBGR.do AmaralESCostaPPereiraKBFilhoAHet al. Chikungunya infection in solid organ transplant recipients. Transplant Proc. (2017) 49:2076–81. 10.1016/j.transproceed.2017.07.004
39.
BouquillardÉCombeB. A report of 21 cases of rheumatoid arthritis following Chikungunya fever. A mean follow-up of two years. Joint bone spine. (2009) 76:654–7. 10.1016/j.jbspin.2009.08.005
40.
HuckeFILBugertJJ. Current and promising antivirals against chikungunya virus. Front Public Health. (2020) 8:618624. 10.3389/fpubh.2020.618624
41.
BattistiVUrbanELangerT. Antivirals against the Chikungunya virus. Viruses. (2021) 13:1307. 10.3390/v13071307
42.
KumarMSudeepABArankalleVA. Evaluation of recombinant E2 protein-based and whole-virus inactivated candidate vaccines against chikungunya virus. Vaccine. (2012) 30:6142–9. 10.1016/j.vaccine.2012.07.072
43.
WangEKimDYWeaverSCFrolovI. Chimeric Chikungunya viruses are nonpathogenic in highly sensitive mouse models but efficiently induce a protective immune response. J Virol. (2011) 85:9249–52. 10.1128/JVI.00844-11
44.
López-CamachoCKimYCBlightJMoreliMLMontoya-DiazEHuiskonenJTet al. Assessment of immunogenicity and neutralisation efficacy of viral-vectored vaccines against chikungunya virus. Viruses. (2019) 11:322. 10.3390/v11040322
45.
TretyakovaIHearnJWangEWeaverSPushkoP. DNA vaccine initiates replication of live attenuated chikungunya virus in vitro and elicits protective immune response in mice. J Infect Dis. (2014) 209:1882–90. 10.1093/infdis/jiu114
46.
ZhaoZDengYNiuPSongJWangWDuWet al. Co-immunization with CHIKV VLP and DNA vaccines induces a promising humoral response in mice. Front Immunol. (2021) 12:655743. 10.3389/fimmu.2021.655743
47.
PlanteKSRossiSLBergrenNASeymourRLWeaverSC. Extended preclinical safety, efficacy and stability testing of a live-attenuated chikungunya vaccine candidate. PLoS Negl Trop Dis. (2015) 9:e0004007. 10.1371/journal.pntd.0004007
48.
KoseNFoxJMSapparapuGBombardiRTennekoonRnde SilvaADet al. A lipid-encapsulated mRNA encoding a potently neutralizing human monoclonal antibody protects against chikungunya infection. Sci Immunol. (2019) 4:eaaw6647. 10.1126/sciimmunol.aaw6647
49.
AugustAAttarwalaHZHimansuSet al. A phase 1 trial of lipid-encapsulated mRNA encoding a monoclonal antibody with neutralizing activity against Chikungunya virus. Nat Med. (2021) 27:2224–33. 10.1038/s41591-021-01573-6
50.
EdelmanRTacketCOWassermanSSBodisonSAPerryJGMangiaficoJA. Phase II safety and immunogenicity study of live chikungunya virus vaccine TSI-GSD-218. Am J Trop Med Hyg. (2000) 62:681–5. 10.4269/ajtmh.2000.62.681
51.
La LinnMAaskovJGSuhrbierA. Antibody-dependent enhancement and persistence in macrophages of an arbovirus associated with arthritis. J GenVirol. (1996) 77:407–11. 10.1099/0022-1317-77-3-407
Summary
Keywords
Chikungunya, pathogenesis, vaccine, epidemiology, prevention
Citation
Cai L, Hu X, Liu S, Wang L, Lu H, Tu H, Huang X and Tong Y (2023) The research progress of Chikungunya fever. Front. Public Health 10:1095549. doi: 10.3389/fpubh.2022.1095549
Received
11 November 2022
Accepted
15 December 2022
Published
09 January 2023
Volume
10 - 2022
Edited by
André Ricardo Ribas Freitas, São Leopoldo Mandic School, Brazil
Reviewed by
Fortino Solórzano-Santos, Federico Gómez Children's Hospital, Mexico
Updates
Copyright
© 2023 Cai, Hu, Liu, Wang, Lu, Tu, Huang and Tong.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Yeqing Tong ✉ t_yeqing@163.comXibao Huang ✉ hxb6407@163.com
†These authors have contributed equally to this work
This article was submitted to Planetary Health, a section of the journal Frontiers in Public Health
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.