Global expansion of Chikungunya Virus: Mapping the 64 year ...

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Accepted Manuscript Title: Global expansion of Chikungunya Virus: Mapping the 64 year history Authors: Braira Wahid, Amjad Ali, Shazia Raque, Muhammad Idrees PII: S1201-9712(17)30089-9 DOI: http://dx.doi.org/doi:10.1016/j.ijid.2017.03.006 Reference: IJID 2895 To appear in: International Journal of Infectious Diseases Received date: 17-1-2017 Revised date: 3-3-2017 Accepted date: 7-3-2017 Please cite this article as: Wahid Braira, Ali Amjad, Raque Shazia, Idrees Muhammad.Global expansion of Chikungunya Virus: Mapping the 64 year history.International Journal of Infectious Diseases http://dx.doi.org/10.1016/j.ijid.2017.03.006 This is a PDF le of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its nal form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Transcript of Global expansion of Chikungunya Virus: Mapping the 64 year ...

Accepted Manuscript

Title: Global expansion of Chikungunya Virus: Mapping the64 year history

Authors: Braira Wahid, Amjad Ali, Shazia Rafique,Muhammad Idrees

PII: S1201-9712(17)30089-9DOI: http://dx.doi.org/doi:10.1016/j.ijid.2017.03.006Reference: IJID 2895

To appear in: International Journal of Infectious Diseases

Received date: 17-1-2017Revised date: 3-3-2017Accepted date: 7-3-2017

Please cite this article as: Wahid Braira, Ali Amjad, Rafique Shazia,Idrees Muhammad.Global expansion of Chikungunya Virus: Mappingthe 64 year history.International Journal of Infectious Diseaseshttp://dx.doi.org/10.1016/j.ijid.2017.03.006

This is a PDF file of an unedited manuscript that has been accepted for publication.As a service to our customers we are providing this early version of the manuscript.The manuscript will undergo copyediting, typesetting, and review of the resulting proofbefore it is published in its final form. Please note that during the production processerrors may be discovered which could affect the content, and all legal disclaimers thatapply to the journal pertain.

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Global expansion of Chikungunya Virus: Mapping the 64 year history

Braira Wahid (M.Phil)1, Amjad Ali (PhD)1*,Shazia Rafique (PhD)1, Muhammad Idrees (PhD)1,2

1Centre for Applied Molecular Biology, 87-West Canal Bank Road Thokar Niaz Baig,

University of the Punjab, Lahore, Pakistan

2Vice Chancellor Hazara University Mansehra, Pakistan

*Corresponding author:

Centre for Applied Molecular Biology, 87-West Canal Bank Road Thokar Niaz Baig, University

of the Punjab, Lahore, Pakistan Tel: +92-42-5293141; Fax: +92-42-5293149; Email: AA:

[email protected]

Email Addresses:

BW: [email protected]

AA: [email protected]

SR:[email protected]

MI: [email protected]

Highlights

CHIKV is a mosquito-transmitted alphavirus

Global distribution shows that CHIKV is expanding at an alarming rate

CHIKV has the potential to spread to new areas because it is travel-associated febrile

illness.

Four different genotypes of CHIKV are Asian, West African, East/Central/South African

(ECSA), and Indian Ocean lineage (IOL).

The disease originated from Africa and then hit the entire globe

This global health menace has affected millions of people in tropical and sub-tropical

world.

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Abstract

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that is emerging as a global

threat because of its highly debilitating nature and unprecedented magnitude. The disease

originated from Africa and then hit the entire globe causing large number of epidemics that

infected millions of people in Asia, Indian subcontinent, Europe, Americas, and Pacific Islands.

According to phylogenetic analysis, four different genotypes of CHIKV are: Asian, West

African, East/Central/South African (ECSA), and Indian Ocean lineage (IOL). In the absence of

well-designed epidemiological studies, this review article aimed to summarize the global

epidemiology of CHIKV and it will provide baseline data for future research in treatment,

prevention, and control of this life threatening disease.

Keywords: CHIKV, epidemiology, Asia, Africa, America, Pacific Islands

Introduction

CHIKV is enveloped, spherical, single stranded positive-sense RNA alphavirus that belongs to

family Togaviridae. Genome size is ∼12 kb and it consists of two open reading frames. Genome

is cleaved into 4 nonstructural proteins (nsP1, nsP2, nsP3, and nsP4) and 5 structural proteins (C,

E3, E2, 6K and E1) [1, 2]. Both glycoproteins E1 and E2 play an important role in viral

replication because E1 glycoprotein is important for membrane fusion. E2 glycoprotein allows

entry of virus into cell through endocytosis [3]. CHIKV is transmitted by Aedes species of

mosquito specifically A. albopictus, A. aegypti, and A. polynesiensis [4-6]. High fever, headache,

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myalgia, arthralgia, poly-arthralgia, hemorrhage, and rash are the typical clinical signs of

CHIKV fever. Several studies report that arthralgia persists for longer periods of time and cause

severe pain in aged people as well as diabetic patients. Individuals with impaired renal function

and alcoholic hepatopathy suffer the most. Significant number of neonates acquire the CHIKV

infection from their mothers due to vertical transmission [7]. Accumulating evidence show the

occurrence of neurological complications as a consequence of CHIKV infection [8-10]. Animal

based experimental studies demonstrate that CHIKV mainly targets fibroblast cells and may also

enter in monocytes and Kupffer cells of liver. The replication of virus depends upon the

defective type 1 IFN-signalling and neonates’ age [7, 11]. Phylogenetic analysis revealed four

different genotypes of CHIKV on the basis of geographical regions. West African genotype

consists of isolates from Senegal and Nigeria. Besides West African genotype, East-Central-

South African (ECSA) is another genotype enzootic in Africa. Isolates from Asian countries are

included in Asian genotype whereas, more recent Indian Ocean lineage (IOL) spread from the

Comoros islands in 2004 and resulted in severe epidemic in Southeast Asia and India in 2005-

2008 [12, 13] (Fig 1).

E1-A226V and E2-L210Q mutations caused a dramatic rise in infectivity of CHIKV and

transmission efficiency of vector CHIKV has spread to Europe and the Americas because of

widespread distribution of A. aegypti and Ae. albopictus [15]. Several studies suggest that the

highly competent vector Ae. albopictus was responsible for CHIK outbreak in La Réunion Island

in 2005-2006. CHIKV can easily be detected by several different methods: viral culture, RT-

PCR, HAI, and ELISA [16-18]. The diagnosis of CHIKV was little bit challenging because the

clinical symptoms of DENV are similar to CHIKV. In order to overcome this challenge,

researchers used multiplex real-time RT-PCR assay that quantitate and detect RNA for all

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CHIKV serotypes and DENV [19]. It has also been reported that patients infected with CHIKV

are more likely to experience maculopaular rash, arthritis/arthralgia, and conjuctival injection

[20]. Moreover, white blood cell count ≥ 5000 cells/mm(3), skin rash during fever, and specific

antigen testing form the basis of differential diagnosis of CHIKV and DENV [21, 22] (Fig 2).

There is no vaccine available yet therefore, preventive measures should be practiced to mitigate

the risk of disease and supportive therapy is equally important as it lessens the severity of disease

[23]. CHIKV has spread to almost 40 countries worldwide and in this review, we discuss the

global epidemiology of CHIKV because of its high morbidity and explosive onset during last

two decades.

The epidemiological pattern of CHIKV includes sporadic as well as epidemic cases in West

Africa from Cameroun to Senegal and in several other African countries (Central African

Republic, South Africa, Angola, Nigeria, Democratic Republic of Congo, South Africa, Malawi,

Guinea, and Uganda). Moreover, number of epidemics occurred in 1960s and 1990s followed by

major outbreaks intermittently occurred with inter-epidemic period ranging from 7 to 20 years.

[23]. The epidemiological pattern of CHIKV includes sporadic as well as epidemic cases.

CHIKV has become distributed worldwide because of prevalence of vectors and their efficiency

at transmitting viruses. Another possible cause of CHIKV spread is travel patterns increasing the

importation of the virus into new geographical regions via viremic people [24].

Epidemiology and global expansion

In Africa, CHIKV was first reported in Tanzania in 1952 followed by several other epidemics in

Central African Republic, Guinea, Burundi, Angola, Uganda, Malawi, Nigeria, Democratic

Republic of Congo and several other states. CHIKV was identified in Tanzania for very first time

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in 1952, followed by another outbreak in South Africa in 1956 [23]. During 1960’s to 1990’s

outbreaks were recorded in Democratic Republic of Congo, Central African Republic, Malawi,

Uganda, Burundi, Angola, Guinea, South Africa, and Nigeria. Almost half million cases were

reported in June 2004 in an outbreak that occurred in Lamu Atoll, Kenya with seroprevalence

rate 70% [25] that was abruptly increased to 75% followed by migration to nearby regions like

Mauritius islands, Seychelles, Comoros, and La Réunion island until March-April 2005. Several

other epidemics occurred in all Southwestern Indian Ocean islands except Madagascar during

2005 to 2007. By January 2006, significant increase in number of CHIKV associated

neurological complications, mortality rate, and fetal infections were observed [26-28]. Two

outbreaks were reported in Reunion Island in 2009 and 2010 [26]. In 2004, two epidemics of

CHIKV infection occurred in Mombasa of which one epidemic that occurred in Lamu infected

13,500 people [29, 30]. In 2011, CHIKV epidemic hit Democratic Republic of Congo (317

cases), Pool (460 cases) and Brazzaville (7,014 cases). Representative of IRIN reported zero

mortality and an approximate count of 8,000 people who were infected with CHIKV [31-34].

During 2004 to 2007, Guinea, Northern Tanzania, Sudan, Gabon, Cameroon and Mbeya Region

experienced several outbreaks [33, 35-38]. Ministry of Health and Social Affairs (MOHSA) of

Senegal reported CHIKV circulation in Kédougou in 2015 [39].

In Asia, CHIKV was first reported in Bangkok, Thailand 1958. The virus spread to other

surrounding regions until 1964 and then re-emerged in 1975 and 1976. About 20 Indian states

experienced several epidemics that resulted in massive disaster. Major outbreaks that increased

concern about CHIKV occurred in India in India in 2005 where it affected 1.4 million people.

More than 1,000,000 cases of CHIKV infection have been reported from different regions of

India during January 2006 to August 2007 and the most patients belonged to Kerala and Tamil

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Nadu. Another smaller epidemic occurred in Indonesia during the same period that affected

about 15,000 people. Yang CF et al., studied 78 imported CHIKV cases identified in Taiwan

during 2006-2014, all strains were similar to strains found in Southern and Southeast Asian

countries because of large number of epidemics occurring during same period and high

frequency of air travel between Taiwan and other countries. In 2009, E1-226V variants of the

ECSA genotype were imported from Indonesia [40]. Since late 2005, severe outbreaks occurred

in Southern and Southeast Asian countries [41-44]. During 2006-2010, ECSA was the most

prevalent genotype found in Indonesia, Thailand, Malaysia, and Singapore whereas, during

2007-2014, Asian genotype was most prevalent in Indonesia and Philippines [44, 45]. In August

2008, forty-five patients in Thailand were confirmed CHIKV positive by PCR, IgM/IgG ELISA

and HAI [46]. Likewise, Cambodia experienced second outbreak in 2011 and study revealed that

25 patients had positive ELISA and RT-PCR for CHIKV [47]. Large number of outbreaks re-

emerged in number of South Asian and Southeast asian countries in 2005-06 and a study

revealed that seroprevalence rate was 4%, 6%, 25%, 27%, and 27.4% in Myanmar, Sri Lanka,

Vietnam, Philippines, and Indonesia respectively [48]. Another study revealed that CHIKV

isolated from Sri Lanka and Singapore during 2006-2008 was imported from India (n=2),

Maldives (n=1), and Malaysia (n=31). The genotype of analyzed strains was ECSA more related

to Indian lineage. Alanine to valine 226 substitution (E1-A226V) was identified in 96%

(133/139) of analysed isolates by genetic characterization of E1 gene sequences [49]. A226V

mutation was reported in La Reunion, North Eastern Italy, and India that allowed the virus to

better adapt to Aedes albopictus, the only competent vector present on the island [50, 51].

In Europe, first autochthonous CHIKV outbreak was first reported in Emilia-Romagna, Italy in

2007. The vector of CHIKV i.e, Aedes albopictus is present in almost 20 European countries.

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East-Central-South African (ECSA) genotype was responsible for emergence of CHIKV in

Europe. Irrespective of the massive influx of travelers back from Americas where Asian CHIKV

genotype had caused around one million cases no Asian-genotype-related autochthonous

transmission of CHIKV in Europe was reported. In 2007, the outbreak of CHIKV in Italy began

with a man from India who developed a febrile syndrome 2 days after his arrival in Italy.

Sequence analysis also revealed that the strain was similar to those detected in Indian

subcontinent [52]. More than 200 cases of CHIKV were confirmed between July 2007 to

September 2007. In 2010, 2013 and 2014, France reported significant number of laboratory-

confirmed autochthonous cases. In 2014, an outbreak of autochthonous CHIKV cases occurred

in France, Puerto Rico, Miami, and Haiti. Some imported cases returning from India were also

confirmed during the same period [53]. CHIKV has spread to almost half of the Pacific Island

countries including Australia, New Zealand, Papua New Guinea, Cook Islands, and Marshall

Islands. The epidemiological findings indicate that the global distribution of Ae. albopictus and

Ae. aegypti well as travelers initiate ongoing transmission in localities previously free of this

infection [54].

In Americas, the emergence of CHIKV occurred in December 2013 in Saint Martin and virus

spread to 17 countries of South America until December 2014. Since it was first reported in Saint

Martin, autochthonous transmission of CHIKV has been identified in 45 countries in Caribbean,

North America, South America and Central America [55]. One case study reported that first case

of CHIKV imported from Sumatra, Indonesia was confirmed in Rio de janeiro, Brazil in 2010

but the virus was not isolated nor demonstrated by PCR [56]. More than 17,000 suspected and

confirmed cases were recorded from December, 2013 to March, 2014 in Caribbean islands and

French Guiana [57]. As of May 16, CDC reported 55,992 travel-related and locally acquired

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cases of CHIKV from 14 islands of French Guiana and Caribbrean [58]. This disastrous outbreak

caused >2.9 million confirmed and suspected cases as well as 296 deaths as of late July 2016. In

December 2013, autochthonous cases of CHIKV were noticed on island of Saint Martin in

Western hemisphere. About fifty confirmed cases of CHIKV were confirmed on Martinique

island. Later on, the infection reached almost 17 countries in America (French Guiana and

Barbuda, British Virgin Islands, Dominican Republic, Guadeloupe, Puerto Rico, Nevis, Saint

Vincent, Grenadines, Guyana, Saint -Barthelemy, Antigua, Martinique, British Virgin Islands,

Saint Martin, Haiti, Anguilla, Saint Lucia, Saint Kitts, and Dominica). The possible source of

CHIKV in US is North American tourists who regularly visit abroad during holidays. The

CHIKV strain isolated from Americas during 2013 and 2014 belonged to Asian genotype and not

to ECSA genotype [59]. In March 2014, more than 15,000 cases were reported in French Guiana,

South America as well as in 9 Caribbean islets in the French West Indies. Until April 2014,

about 6 deaths and total of 35,000 cases were reported in 15 atolls of the Caribbean. In July

2014, survey organized by the Nationwide Institute for Developing and Zoonotic Transmittable

Diseases at the US Centers for Disease Control and Prevention (CDC) revealed 232 imported

cases of CHIKV in US [60]. More than 90% seroprevalence was observed in Suriname in 2014

[61]. 11 locally acquired cases and 272 imported cases were recorded in Florida [62]. Lindsey et

al studied occurrence of CHIKV infections in the United States from 2010 through 2013 and

found that 55 patients out of 115 laboratory-confirmed CHIKV infections had known travel

history. 2 travelled to Africa while 53 travelled to Asia [63]. Total of 895 cases were recorded in

2015 and 143 cases have been reported in United States during recent year 2016 [60, 62]. Recent

studies have reported the emergence of ECSA and Asian genotypes in the Americas [64]. The

detailed account of epidemiological findings is described in table below (Table 1).

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Conclusion

In conclusion, global distribution shows that CHIKV is expanding at an alarming pace and it has

the potential to spread to new areas because it is travel-associated febrile illness. This global

health menace has affected million of people in tropical and sub-tropical world. Temperate

regions may experience severe outbreaks in near future because of presence of potent vector

Aedes albopictus. This dramatic spread of CHIKV in recent highlights the urgent need of

practicing precautionary measures as well as control options. The current status of research with

regard to CHIKV is not encouraging because there is no proper serological test, vaccine,

treatment, and vector control program. Public health officials and medical professionals need to

work on critical areas of research to overcome these challenges so that explosive rise in CHIKV

can be mitigated.

Conflict of interest/Funding: None to declare

References

1. Issac, T.H.K., E.L. Tan, and J.J.H. Chu, Proteomic profiling of chikungunya virus-infected human muscle cells: Reveal the role of cytoskeleton network in CHIKV replication. Journal of proteomics, 2014. 108: p. 445-464.

2. Powers, A.M., et al., Evolutionary relationships and systematics of the alphaviruses. Journal of virology, 2001. 75(21): p. 10118-10131.

3. Voss, J.E., et al., Glycoprotein organization of Chikungunya virus particles revealed by X-ray crystallography. Nature, 2010. 468(7324): p. 709-712.

4. Diallo, M., et al., Vectors of Chikungunya virus in Senegal: current data and transmission cycles. The American journal of tropical medicine and hygiene, 1999. 60(2): p. 281-286.

5. Vanlandingham, D.L., et al., Differential infectivities of o’nyong-nyong and chikungunya virus isolates in Anopheles gambiae and Aedes aegypti mosquitoes. The American journal of tropical medicine and hygiene, 2005. 72(5): p. 616-621.

10

6. Simizu, B., et al., Structural proteins of Chikungunya virus. Journal of virology, 1984. 51(1): p. 254-258.

7. Lenglet, Y., et al., [Chikungunya infection in pregnancy: Evidence for intrauterine infection in pregnant women and vertical transmission in the parturient. Survey of the Reunion Island outbreak]. Journal de gynécologie, obstétrique et biologie de la reproduction, 2006. 35(6): p. 578-583.

8. Chandak, N.H., et al., Neurological complications of Chikungunya virus infection. Neurology India, 2009. 57(2): p. 177.

9. Bandeira, A.C., et al., Neonatal encephalitis due to Chikungunya vertical transmission: First report in Brazil. IDCases, 2016. 5: p. 57-59.

10. Murthy, J., Chikungunya virus: the neurology. Neurology India, 2009. 57(2): p. 113. 11. Couderc, T., et al., A mouse model for Chikungunya: young age and inefficient type-I interferon

signaling are risk factors for severe disease. PLoS Pathog, 2008. 4(2): p. e29. 12. Powers, A.M., et al., Re-emergence of Chikungunya and O’nyong-nyong viruses: evidence for

distinct geographical lineages and distant evolutionary relationships. Journal of General Virology, 2000. 81(2): p. 471-479.

13. Faria, N.R., et al., Epidemiology of chikungunya virus in Bahia, Brazil, 2014-2015. PLoS Currents Outbreaks, 2016.

14. Sahadeo, N., et al., Molecular characterisation of chikungunya virus infections in Trinidad and comparison of clinical and laboratory features with dengue and other acute febrile cases. PLoS Negl Trop Dis, 2015. 9(11): p. e0004199.

15. Tsetsarkin, K.A., et al., A single mutation in chikungunya virus affects vector specificity and epidemic potential. PLoS Pathog, 2007. 3(12): p. e201.

16. Dash, M., I. Mohanty, and S. Padhi, Laboratory diagnosis of chikungunya virus: Do we really need it? Indian journal of medical sciences, 2011. 65(3): p. 83.

17. Shukla, J., et al., Development and evaluation of antigen capture ELISA for early clinical diagnosis of chikungunya. Diagnostic microbiology and infectious disease, 2009. 65(2): p. 142-149.

18. Blacksell, S.D., et al., Poor diagnostic accuracy of commercial antibody-based assays for the diagnosis of acute Chikungunya infection. Clinical and Vaccine Immunology, 2011. 18(10): p. 1773-1775.

19. Cecilia, D., et al., Development of a multiplex real-time RT-PCR assay for simultaneous detection of dengue and chikungunya viruses. Archives of virology, 2015. 160(1): p. 323-327.

20. Mohan, A., et al., Epidemiology, clinical manifestations, and diagnosis of Chikungunya fever: lessons learned from the re-emerging epidemic. Indian journal of dermatology, 2010. 55(1): p. 54.

21. Laoprasopwattana, K., et al., Differential diagnosis of Chikungunya, dengue viral infection and other acute febrile illnesses in children. The Pediatric infectious disease journal, 2012. 31(5): p. 459-463.

22. Beltrán-Silva, S., et al., Clinical and differential diagnosis: Dengue, chikungunya and Zika. Revista Médica del Hospital General de México, 2016.

23. Pialoux, G., et al., Chikungunya, an epidemic arbovirosis. The Lancet infectious diseases, 2007. 7(5): p. 319-327.

24. Johansson, M.A., et al., Nowcasting the spread of chikungunya virus in the Americas. PLoS One, 2014. 9(8): p. e104915.

25. Renault, P., et al., Epidemiology of Chikungunya infection on Reunion Island, Mayotte, and neighboring countries. Médecine et maladies infectieuses, 2012. 42(3): p. 93-101.

26. Borgherini, G., et al., Outbreak of chikungunya on Reunion Island: early clinical and laboratory features in 157 adult patients. Clinical infectious diseases, 2007. 44(11): p. 1401-1407.

11

27. Ramful, D., et al., Mother-to-child transmission of Chikungunya virus infection. The Pediatric infectious disease journal, 2007. 26(9): p. 811-815.

28. Sergon, K., et al., Seroprevalence of chikungunya virus (CHIKV) infection on Lamu Island, Kenya, October 2004. The American journal of tropical medicine and hygiene, 2008. 78(2): p. 333-337.

29. Sutherland, L.J., et al., Serologic evidence of arboviral infections among humans in Kenya. The American journal of tropical medicine and hygiene, 2011. 85(1): p. 158-161.

30. Moyen, N., et al., First reported chikungunya Fever outbreak in the republic of congo, 2011. PLoS One, 2014. 9(12): p. e115938.

31. Irin Chikv Update (2011) CONGO: Chikungunya spreads to Pool region. IRIN. 32. Jentes, E.S., et al., Acute arboviral infections in Guinea, west Africa, 2006. The American journal

of tropical medicine and hygiene, 2010. 83(2): p. 388-394. 33. Hertz, J.T., et al., Chikungunya and dengue fever among hospitalized febrile patients in northern

Tanzania. The American journal of tropical medicine and hygiene, 2012. 86(1): p. 171-177. 34. Gould, L.H., et al., An outbreak of yellow fever with concurrent chikungunya virus transmission in

South Kordofan, Sudan, 2005. Transactions of The Royal Society of Tropical Medicine and Hygiene, 2008. 102(12): p. 1247-1254.

35. Weller, N., et al., Seroprevalence of alphavirus antibodies in a cross-sectional study in southwestern Tanzania suggests endemic circulation of chikungunya. PLoS Negl Trop Dis, 2014. 8(7): p. e2979.

36. Nkoghe, D., et al., Clinical forms of chikungunya in Gabon, 2010. PLoS Negl Trop Dis, 2012. 6(2): p. e1517.

37. Demanou, M., et al., Chikungunya outbreak in a rural area of Western Cameroon in 2006: A retrospective serological and entomological survey. BMC research notes, 2010. 3(1): p. 128.

38. Pistone, T., et al., Cluster of chikungunya virus infection in travelers returning from Senegal, 2006. Journal of travel medicine, 2009. 16(4): p. 286-288.

39. Chikungunya-Senegal. 2015. WHO. 40. Yang, C.-F., et al., Imported Chikungunya Virus Strains, Taiwan, 2006–2014. Emerging infectious

diseases, 2016. 22(11): p. 1981. 41. Schuffenecker, I., et al., Genome microevolution of chikungunya viruses causing the Indian

Ocean outbreak. PLoS Med, 2006. 3(7): p. e263. 42. Yoon, I.-K., et al., High rate of subclinical chikungunya virus infection and association of

neutralizing antibody with protection in a prospective cohort in the Philippines. PLoS Negl Trop Dis, 2015. 9(5): p. e0003764.

43. Sam, I.-C., et al., Chikungunya virus of Asian and central/east African genotypes in Malaysia. Journal of Clinical Virology, 2009. 46(2): p. 180-183.

44. Maha, M.S., N.K. Susilarini, and S. Nur Ika Hariastuti, Chikungunya virus mutation, Indonesia, 2011. Emerging infectious diseases, 2015. 21(2): p. 379.

45. Ministry of Health Republic Indonesia. 2014. Indonesia Health Profile 2013 [cited 2016 Aug 9]. http://www.depkes.go.id/resources/download/pusdatin/profil-kesehatan-indonesia/Indonesia%20Health%20Profile%202013%20-%20v2%20untuk%20web.pdf.

46. Chusri, S., et al., Kinetics of chikungunya infections during an outbreak in Southern Thailand, 2008–2009. The American journal of tropical medicine and hygiene, 2014. 90(3): p. 410-417.

47. Duong, V., et al., Reemergence of Chikungunya virus in Cambodia. Emerg Infect Dis, 2012. 18(12): p. 2066-9.

48. Ngwe, T.M., et al., Retrospective seroepidemiological study of chikungunya infection in South Asia, Southeast Asia and the Pacific region. Epidemiology and infection, 2016: p. 1-8.

49. Hapuarachchi, H., et al., Re-emergence of Chikungunya virus in South-east Asia: virological evidence from Sri Lanka and Singapore. Journal of General Virology, 2010. 91(4): p. 1067-1076.

12

50. CHRETIEN, J.-P., et al., Infection with chikungunya virus in Italy: an outbreak in a temperate region. Commentary. Lancet, 2007. 370(9602).

51. Kumar, N.P., et al., A226V mutation in virus during the 2007 chikungunya outbreak in Kerala, India. Journal of General Virology, 2008. 89(8): p. 1945-1948.

52. Liumbruno, G.M., et al., The Chikungunya epidemic in Italy and its repercussion on the blood system. Blood Transfus, 2008. 6(4): p. 199-210.

53. Delisle, E., et al., Chikungunya outbreak in montpellier, France, September to October 2014. Euro Surveill, 2015. 20(17): p. 21108.

54. Amraoui, F. and A.-B. Failloux, Chikungunya: an unexpected emergence in Europe. Current Opinion in Virology, 2016. 21: p. 146-150.

55. Yactayo, S., et al., Epidemiology of Chikungunya in the Americas. Journal of Infectious Diseases, 2016. 214(suppl 5): p. S441-S445.

56. Albuquerque, I.G.C.d., et al., Chikungunya virus infection: report of the first case diagnosed in Rio de Janeiro, Brazil. Revista da Sociedade Brasileira de Medicina Tropical, 2012. 45(1): p. 128-129.

57. Van Bortel, W., et al., Chikungunya outbreak in the Caribbean region, December 2013 to March 2014, and the significance for Europe. Euro Surveill, 2014. 19(13): p. 20759.

58. Centers for Disease Control and Prevention (2014) Chikungunya in the Americas. 59. Leparc-Goffart, I., et al., Chikungunya in the Americas. The Lancet, 2014. 383(9916): p. 514. 60. Charrel, R., et al., Globalization of Chikungunya: 10 years to invade the world. Clinical

Microbiology and Infection, 2014. 20(7): p. 662-663. 61. van Genderen, F.T., et al., First Chikungunya Outbreak in Suriname; Clinical and Epidemiological

Features. PLoS Negl Trop Dis, 2016. 10(4): p. e0004625. 62. Fischer, M. and J.E. Staples, Notes from the field: chikungunya virus spreads in the Americas—

Caribbean and South America, 2013–2014. MMWR Morb Mortal Wkly Rep, 2014. 63(22): p. 500-1.

63. Lindsey, N.P., et al., Chikungunya Virus Infections Among Travelers–United States, 2010–2013. The American journal of tropical medicine and hygiene, 2015. 92(1): p. 82-87.

64. Nunes, M.R.T., et al., Emergence and potential for spread of Chikungunya virus in Brazil. BMC medicine, 2015. 13(1): p. 1.

65. Michault, A. and F. Staikowsky, Chikungunya: first steps toward specific treatment and prophylaxis. Journal of Infectious Diseases, 2009. 200(4): p. 489-491.

66. Vairo, F., et al., Seroprevalence of dengue infection: a cross-sectional survey in mainland Tanzania and on Pemba Island, Zanzibar. International Journal of Infectious Diseases, 2012. 16(1): p. e44-e46.

67. Chipwaza, B., et al., Dengue and Chikungunya fever among viral diseases in outpatient febrile children in Kilosa district hospital, Tanzania. PLoS Negl Trop Dis, 2014. 8(11): p. e3335.

68. Cavrini, F., et al., Chikungunya: an emerging and spreading arthropod-borne viral disease. The Journal of Infection in Developing Countries, 2009. 3(10): p. 744-752.

69. Ochieng, C., et al., Seroprevalence of infections with dengue, rift valley fever and chikungunya viruses in Kenya, 2007. PLoS One, 2015. 10(7): p. e0132645.

70. Weinbren, M., A. Haddow, and M. Williams, The occurrence of chikungunya virus in Uganda I. Isolation from mosquitoes. Transactions of The Royal Society of Tropical Medicine and Hygiene, 1958. 52(3): p. 253-262.

71. McCrae, A., et al., Chikungunya virus in the Entebbe area of Uganda: isolations and epidemiology. Transactions of The Royal Society of Tropical Medicine and Hygiene, 1971. 65(2): p. 152-168.

72. Centre for Disease Prevention and Control. http://wwwnc.cdc.gov/travel/destinations/clinician/none/malawi.

13

73. Powers, A.M. and C.H. Logue, Changing patterns of chikungunya virus: re-emergence of a zoonotic arbovirus. Journal of General Virology, 2007. 88(9): p. 2363-2377.

74. Adam, A., et al., Low Seroprevalence Indicates Vulnerability of Eastern and Central Sudan to Infection with Chikungunya Virus. Vector-Borne and Zoonotic Diseases, 2016. 16(4): p. 290-291.

75. Desdouits, M., et al., Genetic characterization of Chikungunya virus in the Central African Republic. Infection, Genetics and Evolution, 2015. 33: p. 25-31.

76. Sergon, K., et al., Seroprevalence of Chikungunya virus infection on Grande Comore Island, union of the Comoros, 2005. The American journal of tropical medicine and hygiene, 2007. 76(6): p. 1189-1193.

77. Schwarz, N.G., et al., Seroprevalence of antibodies against Chikungunya, dengue, and Rift Valley fever viruses after febrile illness outbreak, Madagascar. Emerg Infect Dis, 2012. 18(11): p. 1780-6.

78. Ratsitorahina, M., et al., Outbreak of dengue and Chikungunya fevers, Toamasina, Madagascar, 2006. Emerg Infect Dis, 2008. 14(7): p. 1135-7.

79. Peyrefitte, C.N., et al., Chikungunya virus, Cameroon, 2006. Emerging infectious diseases, 2007. 13(5): p. 768.

80. Bacci, A., et al., High Seroprevalence of Chikungunya Virus Antibodies Among Pregnant Women Living in an Urban Area in Benin, West Africa. The American journal of tropical medicine and hygiene, 2015. 92(6): p. 1133-1136.

81. Sissoko, D., et al., Seroprevalence and risk factors of chikungunya virus infection in Mayotte, Indian Ocean, 2005-2006: a population-based survey. PLoS One, 2008. 3(8): p. e3066.

82. Ramchurn, S., et al., A study of the 2006 Chikungunya epidemic outbreak in Mauritius. Internet Journal of Medical Update, 2008. 3(1): p. 11-22.

83. Caron, M., et al., Recent introduction and rapid dissemination of Chikungunya virus and Dengue virus serotype 2 associated with human and mosquito coinfections in Gabon, central Africa. Clinical infectious diseases, 2012. 55(6): p. e45-e53.

84. Horwood, P.F., et al., Outbreak of chikungunya virus infection, vanimo, papua new Guinea. Emerg Infect Dis, 2013. 19(9): p. 1535-8.

85. Collao, X., et al., Different lineages of Chikungunya virus in Equatorial Guinea in 2002 and 2006. The American journal of tropical medicine and hygiene, 2010. 82(3): p. 505-507.

86. Robinson, M., et al., A model for a chikungunya outbreak in a rural Cambodian setting: implications for disease control in uninfected areas. PLoS Negl Trop Dis, 2014. 8(9): p. e3120.

87. Control, C.f.D. and Prevention, Chikungunya outbreak--Cambodia, February-March 2012. MMWR. Morbidity and mortality weekly report, 2012. 61: p. 737.

88. Mavalankar, D., et al., Increased mortality rate associated with chikungunya epidemic, Ahmedabad, India. Emerg Infect Dis, 2008. 14(3): p. 412-415.

89. Cherian, S.S., et al., Evolutionary rates and timescale comparison of Chikungunya viruses inferred from the whole genome/E1 gene with special reference to the 2005–07 outbreak in the Indian subcontinent. Infection, Genetics and Evolution, 2009. 9(1): p. 16-23.

90. Yergolkar, P.N., et al., Chikungunya outbreaks caused by African genotype, India. Emerging infectious diseases, 2006. 12(10): p. 1580.

91. Galate, L.B., et al., Chikungunya fever among patients with acute febrile illness attending a Tertiary Care Hospital in Mumbai. Journal of Laboratory Physicians, 2016. 8(2): p. 85.

92. Ramachandran, V., et al., Chikungunya: a reemerging infection spreading during 2010 dengue fever outbreak in National Capital Region of India. VirusDisease: p. 1-4.

93. Huang, J.-H., et al., Imported chikungunya virus strains, Taiwan, 2006–2009. Emerg Infect Dis, 2009. 15(11): p. 1854-1856.

14

94. Sy, A.K., et al., Molecular Characterization of Chikungunya Virus, Philippines, 2011–2013. Emerging infectious diseases, 2016. 22(5): p. 887.

95. Nisalak, A., et al., Serotype-specific dengue virus circulation and dengue disease in Bangkok, Thailand from 1973 to 1999. The American journal of tropical medicine and hygiene, 2003. 68(2): p. 191-202.

96. Hammon, W.M., A. Rundnick, and G. Sather, Viruses associated with epidemic hemorrhagic fevers of the Philippines and Thailand. science, 1960. 131(3407): p. 1102-1103.

97. Pongsiri, P., et al., Entire genome characterization of Chikungunya virus from the 2008–2009 outbreaks in Thailand. Trop Biomed, 2010. 27(2): p. 167-176.

98. Kosasih, H., et al., Evidence for endemic chikungunya virus infections in Bandung, Indonesia. PLoS Negl Trop Dis, 2013. 7(10): p. e2483.

99. Thaung, U., et al., Epidemiological features of dengue and chikungunya infections in Burma. The Southeast Asian journal of tropical medicine and public health, 1975. 6(2): p. 276-283.

100. Tun, M.M.N., et al., Detection of east/central/south African genotype of chikungunya virus in Myanmar, 2010. Emerging infectious diseases, 2014. 20(8): p. 1378.

101. Zheng, K., et al., Genetic analysis of chikungunya viruses imported to mainland China in 2008. Virology journal, 2010. 7(1): p. 1.

102. Wu, D., et al., Chikungunya outbreak in Guangdong province, China, 2010. Emerg Infect Dis, 2012. 18(3): p. 493-5.

103. Qiaoli, Z., et al., Maiden outbreak of chikungunya in Dongguan city, Guangdong province, China: epidemiological characteristics. PLoS One, 2012. 7(8): p. e42830.

104. Azami, N.A.M., et al., Emergence of chikungunya seropositivity in healthy Malaysian adults residing in outbreak-free locations: Chikungunya seroprevalence results from the Malaysian Cohort. BMC infectious diseases, 2013. 13(1): p. 1.

105. Sam, I.-C., et al., Genotypic and phenotypic characterization of Chikungunya virus of different genotypes from Malaysia. PLoS One, 2012. 7(11): p. e50476.

106. Pfeffer, M., et al., Chikungunya fever in two German tourists returning from the Maldives, September, 2009. 2010.

107. Yoosuf, A.A., et al., First report of chikungunya from the Maldives. Transactions of The Royal Society of Tropical Medicine and Hygiene, 2009. 103(2): p. 192-196.

108. Razmy, A.M., Clinical features of chikungunya infection in Sri Lanka. Asian Pacific Journal of Tropical Disease, 2014. 4(2): p. 131-134.

109. Ng, L.-C., et al., Entomologic and virologic investigation of Chikungunya, Singapore. Emerg Infect Dis, 2009. 15(8): p. 1243-1249.

110. Lim, P.L., H. May‐Lin Oh, and E.E. Ooi, Chikungunya in Singapore: imported cases among travelers visiting friends and relatives. Journal of travel medicine, 2009. 16(4): p. 289-291.

111. Darwish, M.A., et al., A sero-epidemiological survey for certain arboviruses (Togaviridae) in Pakistan. Transactions of The Royal Society of Tropical Medicine and Hygiene, 1983. 77(4): p. 442-445.

112. Afzal, M.F., et al., Chikungunya fever among children presenting with nonspecific febrile illness during an epidemic of dengue fever in Lahore, Pakistan. 2015.

113. Hassan, R., et al., Chikungunya–an emerging infection in Bangladesh: a case series. Journal of medical case reports, 2014. 8(1): p. 1.

114. Khatun, S., et al., An outbreak of chikungunya in rural Bangladesh, 2011. PLoS Negl Trop Dis, 2015. 9(7): p. e0003907.

115. Madani, T.A., et al., Outbreak of viral hemorrhagic fever caused by dengue virus type 3 in Al-Mukalla, Yemen. BMC infectious diseases, 2013. 13(1): p. 1.

15

116. Ciccozzi, M., et al., Phylogeny of dengue and Chikungunya viruses in Al Hudayda governorate, Yemen. Infection, Genetics and Evolution, 2014. 27: p. 395-401.

117. Thabet, A.A., et al., Epidemiological Characterization of Chikungunya Outbreak in Lahj Governorate, Southern Yemen. Journal of Community Medicine & Health Education, 2013. 2013.

118. Fahmy, N.T., et al., Complete genome sequence of chikungunya virus isolated from an Aedes aegypti mosquito during an outbreak in Yemen, 2011. Genome announcements, 2015. 3(4): p. e00789-15.

119. Wangchuk, S., et al., Chikungunya fever outbreak, Bhutan, 2012. Emerg Infect Dis, 2013. 19(10): p. 1681-4.

120. Phimmasine, S., et al., Emergence of chikungunya in Moonlapamok and Khong Districts, Champassak Province, the Lao People’s Democratic Republic, May to September 2012. EDITORIAL TEAM, 2013. 4(1): p. 46.

121. Phommanivong, V., et al., Co-circulation of the dengue with chikungunya virus during the 2013 outbreak in the southern part of Lao PDR. Tropical Medicine and Health, 2016. 44(1): p. 24.

122. Hussain, R., I. Alomar, and Z. Memish, Chikungunya virus: emergence of an arthritic arbovirus in Jeddah, Saudi Arabia. Eastern Mediterranean Health Journal, 2013. 19(5): p. 506.

123. Aoyama, I., et al., A case of chikungunya fever imported from India to Japan, follow-up of specific IgM and IgG antibodies over a 6-month period. Jpn J Infect Dis, 2010. 63(1): p. 65-66.

124. Tsuboi, M., Autochthonous Chikungunya Fever in Traveler Returning to Japan from Cuba. 125. Gibney, K.B., et al., Chikungunya fever in the United States: a fifteen year review of cases. Clinical

infectious diseases, 2011: p. ciq214. 126. Figueiredo, M.L.G.d. and L.T.M. Figueiredo, Emerging alphaviruses in the Americas: Chikungunya

and Mayaro. Revista da Sociedade Brasileira de Medicina Tropical, 2014. 47(6): p. 677-683. 127. Cauchemez, S., et al., Local and regional spread of chikungunya fever in the Americas. Euro

surveillance: bulletin Européen sur les maladies transmissibles= European communicable disease bulletin, 2014. 19(28): p. 20854.

128. Madariaga, M., E. Ticona, and C. Resurrecion, Chikungunya: bending over the Americas and the rest of the world. The Brazilian Journal of Infectious Diseases, 2016. 20(1): p. 91-98.

129. Carbajo, A.E. and D. Vezzani, Waiting for chikungunya fever in Argentina: spatio-temporal risk maps. Memórias do Instituto Oswaldo Cruz, 2015. 110(2): p. 259-262.

130. Parreira, R., et al., Dengue virus serotype 4 and chikungunya virus coinfection in a traveller returning from Luanda, Angola, January 2014. Chikungunya and Zika virus, 2013. 54: p. 9.

131. Macpherson, C., et al., Clinical and Serological Insights from the Asian Lineage Chikungunya Outbreak in Grenada, 2014: An Observational Study. The American journal of tropical medicine and hygiene, 2016. 95(4): p. 890-893.

132. Mattar, S., et al., Outbreak of Chikungunya virus in the north Caribbean area of Colombia: clinical presentation and phylogenetic analysis. The Journal of Infection in Developing Countries, 2015. 9(10): p. 1126-1132.

133. Shiferaw, B., et al., The Chikungunya Epidemic: A look at five cases. IDCases, 2015. 2(4): p. 89-91. 134. Díaz, Y., et al., Chikungunya virus infection: first detection of imported and autochthonous cases

in Panama. The American journal of tropical medicine and hygiene, 2015. 92(3): p. 482-485. 135. Nava-Frías, M., et al., Chikungunya fever: current status in Mexico. Boletín Médico del Hospital

Infantil de México, 2016. 73(2): p. 67-74. 136. Díaz-Quiñonez, J.A., et al., Identification of Asian genotype of chikungunya virus isolated in

Mexico. Virus Genes, 2016. 52(1): p. 127-129. 137. Feldstein, L.R., et al., The First Reported Outbreak of Chikungunya in the US Virgin Islands, 2014–

2015. The American journal of tropical medicine and hygiene, 2016. 95(4): p. 885-889.

16

138. CDC, 2014 final data for the United States. http://www.cdc.gov/chikungunya/geo/united-states-2014.html.

139. Edwards, T., et al., Co-infections with Chikungunya and Dengue Viruses, Guatemala, 2015. 140. World Journal Organization, Chikungunya – Argentina. http://www.who.int/csr/don/14-march-

2016-chikungunya-argentina/en/. 141. Rezza, G., et al., Infection with chikungunya virus in Italy: an outbreak in a temperate region. The

Lancet, 2007. 370(9602): p. 1840-1846. 142. Beltrame, A., et al., Imported chikungunya infection, Italy. Emerg Infect Dis, 2007. 13(8): p. 1264-

1266. 143. Grandadam, M., et al., Chikungunya virus, southeastern France. Emerging infectious diseases,

2011. 17(5): p. 910-914. 144. Dupont-Rouzeyrol, M., et al., Chikungunya virus and the mosquito vector Aedes aegypti in New

Caledonia (South Pacific Region). Vector-Borne and Zoonotic Diseases, 2012. 12(12): p. 1036-1041.

145. Ledermann, J.P., et al., Aedes hensilli as a potential vector of Chikungunya and Zika viruses. PLoS Negl Trop Dis, 2014. 8(10): p. e3188.

146. World Health Organization, http://www.wpro.who.int/southpacific/about/sids-faq-chikungunya.pdf.

147. Relief Web. http://reliefweb.int/report/tokelau/tokelau-recovers-chikungunya. 148. Nelson, J., et al., Encephalitis caused by Chikungunya virus in a traveler from the Kingdom of

Tonga. Journal of clinical microbiology, 2014. 52(9): p. 3459-3461. 149. Nhan, T.-X., et al., Chikungunya virus imported into French polynesia, 2014. Emerg Infect Dis,

2014. 20(10): p. 1773-4. 150. Oehler, E., et al., Increase in cases of Guillain-Barre syndrome during a Chikungunya outbreak,

French Polynesia, 2014 to 2015. Euro Surveill, 2015. 20: p. 48. 151. Radio New Zealand International. http://www.radionz.co.nz/international/pacific-

news/265460/cook-islands-confirms-chikungunya-cases 152. Radio New Zealand. http://www.radionz.co.nz/international/pacific-news/266602/over-3,000-

chikungunya-cases-in-kiribati.

17

Fig 1: Maximum clade credibility (MCC) phylogeny based on the complete coding region of 74

CHIKV sequences. CHIKV isolated during epidemic that occurred in Indian Ocean in 2005 and

2006 was novel ECSA with mutation from alanine to valine at position 226 in the E1 envelope

glycoprotein gene (E1-A226V) and was subsequently described as the Indian Ocean Lineage

(IOL) [14].

18

Fig 2: Diagnostic criteria for CHIKV

19

Table 1: Epidemiological findings of CHIKV across the globe

Country Epidemiological findings Genotype Ref.

Africa

Zimbabwe Since 1952 several epidemics reported in Zimbabwe. Large

outbreak occurred during 1999-2000. Several cases of local

transmission were documented in late 2013 and 2016.

ECSA [65]

Tanzania The first outbreak of CHIKV was recorded in Makonde

Plateau, Tanzania in 1952. Combined outbreak of DENV and

CHIKV has recently been recorded in 2011-2014. About 7.7%

and 1.8% seroprevalence was found in Pemba Island and

Tosamaganga, respectively.

ECSA [33,

66,

67]

Nigeria An epidemic that affected thousands of people occurred in

1969.

Burundi First outbreak was reported in 1980-1982. ECSA [68]

Kenya First outbreak occurred in 1982 followed by other severe

epidemics with attack rate 75% in Lamu and Mombasa in 2004

. Over 150 Kenyan people have died because of CHIKV.

Combined outbreak of DENV and CHIKV has been recorded

in 2013.

ECSA

IOL

[28,

69]

Senegal First outbreak occurred in 1983 followed by number of

outbreaks till 1999. Few more cases were identified in 2006.

ECSA

West

African

[38]

Uganda Uganda experienced several outbreaks during 1985-1971. ECSA [70,

71]

Malawi First outbreak occurred in 1987-89. Few cases were reported in

2001 and 2015.

ECSA [72,

73]

Sudan About 12% population was positive for CHIKV in 1989.

Another outbreak occurred in 2005, 2012, and 2013.

Seroprevalence 1.8% has recently been reported in 2016.

Not

studied

[74]

Central

African

Republic

Outbreak occurred in 2000–2003 that infected thousands of

people.

ECSA

[75]

Comoros Comoros experienced severe outbreak in 2005 with 60%

infection rate.

IOL [76]

Madagascar Two epidemics that occurred in 2006 and 2009 have been

recorded. The IgG and IgM seroprevalence varied between

5% to 45%.

ECSA

IOL

[77,

78]

Cameroon CHIKV was reported in 2006 in two main countries i.e,

Douala and Yaoundé. Seroprevalence was 51.4% in 2006.

ECSA [37,

79]

Benin Seroprevalence was 36.1% in 2006 and 2007. Not

studied

[80]

Mayotte Only outbreak was reported in 2005-06 with seroprevalence

37·2%.

Not

studied

[81]

Mauritius Mauritius experienced major epidemic in 2005-06 and about ECSA [82]

20

51% of population was suspected to have CHIKV. IOL

Gabon In 2010, 36.6% of total 4287 suspected cases had confirmed

CHIKV.

ECSA [36,

83]

Guinea First outbreak occurred in June 2012 almost 36% of population

was positive for CHIKV.

ECSA

West

African

[84]

Congo First outbreak occurred in 2011. As of 26th July, 2014

approximately 11,083 suspected cases were reported of which

maximum cases were reported from Makélékélé, Brazzaville.

ECSA

[30,

75]

Equatorial

Guinea

More than 100 cases of CHIKV were documented during

2002-2006. In 2012, Papua New Guinea experienced severe

outbreak that spread to 8 provinces.

ECSA [84,

85]

Asia

Cambodia First case was identified in 1961 and the virus re-emerged in

2011when 24 patients had positive RT-PCR and ELISA. In

2012, another outbreak occurred in Trapeang Roka Kampong

Speu with the seroprevalence rate of 44.7%.

Asian

ECSA

IOL

[47,

86,

87]

India

First outbreak occurred in Kolkata in 1963 followed by

number of other outbreaks in Maharashtra, Andhra Pradesh,

Tamil Nadu and Barsi from 1964 to 1973. The virus

reappeared in 2006 and badly hit 13 Indian states including

Gujrat, Kerala, Tamil Nadu, Andhra Pardesh, Madhyapardesh,

Maharashtra, and Karnatka. About 2,994 individuals out of

total 60,777 suspected chikungunya cases lost their lives.

Lakshadweep experienced small outbreak in 2007. One lac

people were again infected with CHIKV in 2008 in Kerala.

During subsequent years several other large outbreaks

occurred in Maharashtra, Andaman & Nicobar Islands, West

Bengal, Orissa, Rajasthan, and Puducherry. In 2010,

seroprevalence rate was 9.91% in National Capital Region of

India. Mumbai reported 12.5% seroprevalence in the recent

year 2016.

Asian

ECSA

African

IOL

[88-

93]

Phillipines CHIKV was first identified in 1965 followed by several

sporadic cases in Masbate, Cebu, Cavite, Luzon Island, and

Mindanao.

Asian

ECSA

[94]

Vietnam CHIKV was first identified in 1960s mainly associated with

Veitnam War. In 1966, 10 American soldiers were infected

with CHIKV. In 1967, anti-CHIKV antibodies were detected

in large number of children.

Asian

Thailand 46,000 suspects were reported in 1960s. In 2008, 244 people

had confirmed CHIKV. Approximately 31% population was

infected in 1962 Bangkok outbreak. Bueng Kan experienced

severe outbreak in 2013.

Asian

ECSA

IOL

[93,

95-

97]

Indonesia In 1972, CHIKV was reported in East Sumatera, Kalimantan,

Bali, Java, Sulawesi, and Flores. From 2002-2008, CHIKV

Asian [93,

98]

21

was confirmed in West Java and Bandung, Annual bioburden

has never exceeded 5000 cases. Overall incidence rate was

found to be 10.1 cases per 1,000 persons per year.

Burma High prevalence of CHIKV was confirmed in 1973 in

Myanmar, Mandalay Divisions and Kachin, Arakan and Shan

States, Sagaing Division, and Rangoon, Magwe and

Tenasserim Divisions. Another study carried out in 2010

revealed that in Myanmar about, 6% of DENV patients had

CHIKV.

Asian

ECSA

[99,

100]

China First case was reported in 1987 in Yunnan Province followed

by several other small outbreaks that occurred in 2008.

Another major outbreak has also been reported in 2010 in

Guangdong Province. Approximately 78 imported cases of

CHIKV fever have been recorded in Taiwaan during 2006-14.

Asian

ECSA

IOL

[93,

101-

103]

Malaysia Several outbreaks have been reported in Port Klang (1998),

Bagan Pachor (2006), Ipoh, Perak (2006) and Johor (2008).

The seroprevalence rate was found to be 5.9% in 2009. 34

cases were confirmed in 2008 in rural Malaysia.

Asian

ECSA

IOL

[43,

93,

104,

105]

Maldives First outbreak occurred in late 2006 and 2007 with 12,000

suspected cases of CHIKV. Incidence rate was found to be 82

to 722 people per 1,000 population. In 2009, CHIKV was

confirmed in two German travelers back from Maldives.

Asian

IOL

[93,

106,

107]

Sri Lanka After 40 years hiatus, CHIKV re-emerged in Sri Lanka in 2007

with >37,000 suspected cases. The surveillance of CHIKF in

Sri Lankan population was 89.2%.

Asian

ECSA

IOL

[49,

108]

Singapore First outbreak that occurred in 2008 infected about 1000

people. Singapore experienced another outbreak in 2013.

Asian

ECSA

IOL

[49,

93,

109,

110]

Brunei,

Darussalam

and Sabah

348 were confirmed in 2009 in Sabah but only one case has

been reported in Brunei, Darussalam in 2011.

Not yet

studied

Pakistan A study revealed that overall prevalence rate of Royal farm

virus, Uganda virus, and CHIKV ranged between 1.3% to

1.6%. Few cases of CHIKV were confirmed during the DENV

outbreak occurred in 2011.

Not yet

studied

[111,

112]

Bangladesh First outbreak was reported in 2011 with an estimated

prevalence of 29%.

Only six confirmed cases of CHIKV were reported in 2014.

Asian

ECSA

[93,

113,

114]

Yemen First case was reported from Bait-Al Faqih in Oct 2011. In

2011, about 104 deaths were recorded in outbreak occurred in

Al-Hudaydah. 13 cases of CHIKV were confirmed in 2012 in

Al-Hawtah district, Lahj Governorate, Southern Yemen.

Asian

ECSA

[115-

118]

Bhutan 78 suspected cases were reported in 2012 outbreak. Asian

ECSA

IOL

[119]

22

Laos In 2012, 31 out of 197 suspected cases from Moonlapamok

and Khong Districts of Champassak Province, Laos had

confirmed CHIKV. Several cases of DENV and CHIKV co-

infection were documented during 2013 outbreak occurred in

Lao PDR.

ECSA [120,

121]

Saudi Arabia Only one case of CHIKV has been confirmed yet in 2013. Asian [122]

Japan 14 laboratory-confirmed cases were documented in 2013.

Autochthonous transmission of CHIKV fever has been

confirmed recently in traveler returned from Cuba. Another

case was imported from India in 2010.

Asian

ECSA

[123,

124]

Americas

United States Only 109 laboratory-confirmed CHIK cases were identified

from 1995 through 2009.

ECSA

Asian

[125]

Dominica About 417 cases were recorded between December 15th, 2013

and March 11th, 2014.

ECSA

Asian

[126]

Guadeloupe 24,428 cases of CHIKV fever were confirmed in 2013 and the

incidence rate was 52 per 1000.

ECSA

Asian

[127]

Saint

Maarten

Cumulative estimated number of cases until December 2013,

was 425. Several cases of chikungunya fever have been

reported in 2014 and 2015.

ECSA

Asian

[128]

Dominican

Republic

Total of 38,656 cases were reported in 2013 outbreak. 112

cases have been reported in 2016.

ECSA

Asian

[129]

Anguilla The autochthonous cases CHIKV fever were confirmed in

Anguilla in 2013. Cumulative estimated number of cases until

February, 2014 was 49.

ECSA

Asian

[62,

130]

Saint

Barthelemy

The incidence rate 74 cases per 1000 population was reported

in 2013 outbreak.

ECSA

Asian

[127]

Antigua and

Barbuda

The autochthonous cases CHIKV fever were confirmed in

Antigua and Barbuda in 2013. Cumulative estimated number

of cases until April, 2014 was 1394.

ECSA

Asian

[126]

Aruba Few cases of CHIKV fever were documented during 2014

outbreak. Cumulative estimated number of cases until March,

2014 was 203.

ECSA

Asian

[126]

Bahamas Few cases were reported in July, 2014. ECSA

Asian

[126]

Grenada About 500 cases of CHIKV were documented in 2014. ECSA

Asian

[131]

Barbados Few cases were reported in 2014 and none of any evidence of

CHIKV fever was reported afterwards.

ECSA

Asian

[126]

Belize Belize experienced CHIKV for very first time in 2014, 58

cases have now been reported in 2016.

ECSA

Asian

[126]

Cayman

Islands

Cumulative estimated number of cases until August, 2014 was

25. Several cases of chikungunya fever have been reported in

2015 and 2016.

Asian [126,

132]

Colombia Cumulative estimated number of cases until November, 2014

was 22,372. To March 2015, 1317 confirmed cased of CHIKV

Asian [126,

132]

23

fever were documented.

El Salvador Cumulative estimated number of cases until November, 2014

was 123,339. About 5840 cases have been reported in 2016.

ECSA

Asian

[133]

French

Guiana

Several cases of local transmission of chikungunya have been

reported in 2014, 2015 and 2016. Cumulative estimated

number of cases until February, 2014 was 7870.

ECSA

Asian

[126]

Haiti Total of 6,318 cases were reported in 2013 outbreak.

Significant bioburden was recorded in April, 2014.

ECSA

Asian

[129]

Martinique 30,715 of CHIKV fever were confirmed in 2013 and the

incidence rate was 76 per 1000.

ECSA

Asian

[127]

Saint Martin 4,113 of CHIKV were reported in 2013. Seroprevalence was

found to be 16.9% and the incidence was 115 cases per 1000

population.

ECSA

Asian

[127]

Panama Two cases were confirmed in May 2014. Cumulative

estimated number of cases until July 2014, was 32.

ECSA

Asian

[134]

Montserrat Several cases of chikungunya fever have been reported in 2014

and 2015.

ECSA

Asian

[126]

Nicaragua Several cases of chikungunya fever have been reported in 2014

and 2015.

ECSA

Asian

[126]

Paraguay To March 2015, 130 confirmed cased of CHIKV fever were

documented.

ECSA

Asian

[128]

Honduras Several cases of chikungunya fever have been reported in 2014

and 2015. Co-infection of both ZIKV and CHIKV has recently

been reported in 2016.

ECSA

Asian

[61]

Jamaica Several cases of CHIKV fever have been reported in 2014 and

2015. Cumulative estimated number of cases until August,

2014 was 1098.

ECSA

Asian

[126]

Mexico 222 cases were reported in 2014 followed by 11,394 cases in

2015. About 536 cases have been confirmed in 2016.

ECSA

Asian

[135,

136]

Saint Lucia Several cases of chikungunya fever have been reported in 2014

and 2015. Cumulative estimated number of cases until April,

2014 was 896.

ECSA

Asian

[126]

Saint Vincent

and the

Grenadines

Several cases of chikungunya fever have been reported in 2014

and 2015. Cumulative estimated number of cases until April,

2014 was 494.

ECSA

Asian

[126]

Ecuador To March 2015, 213 confirmed cased of CHIKV fever were

documented.

ECSA

Asian

[129]

Suriname Suriname experienced first outbreak in 2014 and the

cumulative estimated number of cases was 1210 followed by

several other cases in 2015 and 2016.

ECSA

Asian

[126]

Trinidad and

Tobago

Several cases of chikungunya fever have been reported in 2014

and 2015. Cumulative estimated number of cases until August,

2014 was 177.

ECSA

Asian

[126]

Turks and

Caicos

Islands

Several cases of chikungunya fever have been reported in 2014

and 2015. Cumulative estimated number of cases until July,

2014 was 19.

ECSA

Asian

[126]

24

US Virgin

Islands

First outbreak was reported in 2014-15. Incidence was 1.8

cases per 1,000 population among individuals aged 0-14 years

and 13.1 cases per 1,000 population among individuals aged

55-64 years.

ECSA

Asian

[137]

Puerto Rico 32 travelled associated cases and 4,242 cases were confirmed

in 2014. 227 cases were recorded in 2015. About 142 cases

have been reported in the recent year 2016. Cumulative

estimated number of cases until May, 2014 was 20,073.

ECSA

Asian

[138]

Guatemala Several cases of CHIKV fever have been reported in 2014 and

2015.

ECSA

Asian

[139]

Guyana Several cases of CHIKV fever have been reported in 2014 and

2015. Cumulative estimated number of cases until May, 2014

was 76.

ECSA

Asian

British

Virgin Island

Several cases of chikungunya fever have been reported in 2015

and 2016. Cumulative estimated number of cases until January

2014 was 44.

ECSA

Asian

[126]

Saint Kitts

and Nevis

Several cases of chikungunya fever have been reported in 2014

and 2015. Cumulative estimated number of cases until

February, 2014 was 459.

ECSA

Asian

[126]

Bolivia To March 2015, 204 confirmed cased of CHIKV fever were

documented.

ECSA

Asian

[129]

Brazil To March 2015, 149 confirmed cased of CHIKV fever were

documented. 3394 cases have been recorded in 2016.

ECSA

Asian

[129]

Peru 8 cases have been reported in 2016. ECSA

Asian

[128]

Argentina 21 and 55 laboratory-confirmed cases of CHIKV have been

reported in 2015 and 2016, respectively.

ECSA

Asian

[140]

Venezuela To March 2015, 2,303 confirmed cased of CHIKV fever were

documented. 3,107 cases have been reported in 2016.

ECSA

Asian

[129]

Europe

Italy 205 cases were confirmed in 2007 outbreak in Castiglione di

Cervia and Castiglione di Ravenna. From July to September

2006, 17 confirmed cases were observed in travelers.

ECSA

IOL

[52,

141,

142]

France First imported case of CHIKV was recorded in 2007. In 2010,

France faced simultaneous outbreaks of CHIKV and DENV.

In 2014, 11 confirmed cases, 12 autochthonous cases, and 1

confirmed case was identified in Montpellier, France. About

30% population of La Reunion Island was positive for

CHIKV.

ECSA

IOL

[53,

143]

Oceania/Pacific Islands

New

Caledonia

CHIKV was first detected in 33 people in 2011. Several other

cases were recorded in 2013 and 2014.

Not yet

studied

[144]

Papua New

Guinea

CHIKV was first time reported in late June, 2012 and during

subsequent years more than 1000 cases were recorded.

Not yet

studied

[84]

Federated

States of

Severe outbreak that affected hundreds of people was recorded

in late 2013.

Not yet

studied

[145]

25

Micronesia

New

Caledonia

CHIKV was first detected in 33 people in 2011. Several other

cases were recorded in 2013 and 2014.

Not yet

studied

[144]

Samoa About 308 confirmed cases of CHIKV were documented in

2014.

Not yet

studied

[146]

Tokelau About 200 people acquired CHIKV in 2014. Not yet

studied

[147]

American

Samoa

American Samoa reported its first outbreak in November 2014

with 2500 confirmed cases.

Not yet

studied

[138]

Tonga One imported case of CHIKV was reported in March 2014. Not yet

studied

[148]

French

Polynesia

CHIKV was imported to French Polynesia in 2014 followed

by several other cases reported during November, 2014 to

March 2015.

Not yet

studied

[149,

150]

Cook Islands About 597 cases were reported in 2014-2015. Not yet

studied

[151]

Kiribati About 3,000 confirmed cases of CHIKV had been reported till

late 2015.

Not yet

studied

[152]