Four cases of acute chikungunya virus infection (CHIKV) were reported among European citizens returning from Bali through the GeoSentinel Surveillance and Research Network. All travelers returned from Bali between May and June 2022.
The four cases reported, two male and two female, were aged between 24 and 37 years. One case was an expatriate and three were tourists. All four presented between March 27th and June 21st, 2022 to one of four GeoSentinel sites (Amsterdam, Barcelona, Munich and Paris) and had a probable or confirmed CHIKV infection with positive serum PCR, or a seroconversion with declining IgM and rising IgG in paired samples (Table 1). One case had a CHIKV infection diagnosed in Bali (unknown diagnostic method). No acute co-infection with dengue virus or Zika virus were reported in the three cases diagnosed at the GeoSentinel sites, but one case had false-positive Zika IgM which turned out negative upon repetition two weeks later. All four patients reported acute symptoms typical of chikungunya including fever, arthralgias and a rash. Three had a maculopapular rash and one an unspecified exanthema. Of note, all patients reported prolonged or recurrent arthralgias for which non-steroidal anti-inflammatory drugs (NSAIDs) were prescribed. In two cases, the infection was most probably acquired in Canggu in the south of the island, about 8 km west of Denpasar; in the other two cases the probable location could not be specified further.
Table 1. Epidemiological, clinical and diagnostic characteristics of confirmed and probable chikungunya cases in travelers from Bali presenting at GeoSentinel sites.
Case Age (Sex) Most probable place where infection was acquired Travel period (Date of symptom onset) Acute Symptoms Complications, treatment Chikungunya diagnostic method Additional arboviral diagnostic test results Outcome (Last date assessed)
1 24 (F) Canggu/Bali/Indonesia 04/05/2022–28/05/2022 (12/05/2022) Fever/generalized, pruritic maculopapular rash/arthralgias (bilateral small joints finger, wrist, knee, ankle) prolonged arthralgias (3 months), treatment with NSAIDs IgM 1:320 (<1:20)/IgG 1:160 (<1:20) (01/06/22) IgM 1:160 (<1:20)/IgG 1:320 (<1:20) (14/06/22) Dengue IgM (−)/IgG(+), NS 1 (−), PCR (−) Zika IgM(−)/IgG (−) full recovery (01/09/2022)
2 37 (M) Canggu/Bali/Indonesia Expatriate (27/03/2022) Fever, exanthema, generalized arthralgias prolonged arthralgias (5 months) with ankle swellings, treatment with NSAID Unknown (Diagnosis established in Bali)a Unknown full recovery (31/08/2022)
3 30 (M) Bali/Indonesia 06/06/2022–21/06/2022 (18/06/2022) Fever, maculopapular rash, arthralgia (bilateral: wrists), headache, lymphadenopathy (bilateral: latero-cervical, occipital, axillary and inguinal) prolonged arthralgia (>2 months) (wrists, metacarpophalangeal joints, knee), treatment with NSAIDs PCR (+), IgM(+)/IgG (−) (23/6/2022) IgM (+)/IgG(+) (07/07/2022) Dengue IgM-/IgG -, NS 1-, PCR (−) Zika PCR (−), IgM(+)/IgG(−) (23/06/22) Zika IgM(−)/IgG(−) (07/07/2022 full recovery (19/10/2022)
4 32 (F) Bali/Indonesia 06/06/2022–21/06/2022 (21/06/2022) Fever, generalized non-pruritic maculopapular rash, arthralgias (bilateral wrist, knee, ankle) relapsing and persistent arthralgias, treatment with NSAIDs PCR (+), IgM (−)/IgG (−) (23/06/22) CHIKV IgM (+)/IgG(+) (06/07/22) Dengue IgM(−)/IgG (−), NS 1(−) full recovery (21/09/2022)
a
According to the patient, the diagnosis was laboratory-confirmed on Bali; however, the patient did not carry written documentation with him when presenting for follow-up in Amsterdam.
Chikungunya virus is an alphavirus of the family Togaviridae, transmitted between humans through female Aedes spp. mosquitoes, especially Ae. aegypti and Ae. albopictus.
CHIKV was first identified during an outbreak in Tanzania in 1952 [1]. In the Asia-Pacific region, CHIKV was first reported from the Philippines in 1954, with subsequent outbreaks in various countries in southern and southeast Asia. The earliest report of chikungunya in Indonesia dates back to 1973. In the last two decades, outbreaks have been reported in several areas of Indonesia including Bali, in 2009–2011, and in Northern Bali in 2015–2016 [2].
In two of our reported cases, the most probable place CHIKV infection was acquired was Canggu. On the date of symptom onset, both patients were staying in Ubud, about 25 km north of Denpasar where Ubud Monkey Forest is a major tourist attraction. This shows how tourist mobility and labor flow is an important factor in local spread of infectious diseases. In addition, viremic visitors to Ubud Monkey Forest constitute a reverse zoonotic potential, that may affect the local long-tailed macaques (Macaca fascicularis) and create a CHIKV reservoir. Antibodies against CHIKV have been reported in long-tailed macaques from elsewhere in the region [3].
Another concern is the risk of autochthonous transmission of arboviruses by returning viremic travelers to non-endemic home countries where suitable mosquito vectors are present and very active during the summer period when the described case series took place.
In Europe, the first outbreak of autochthonous CHIKV infections was reported from Italy in 2007, after the virus was introduced by a traveler. More than 200 cases were reported in this outbreak. In 2017 the second cluster of autochthonous transmission of chikungunya virus with 270 confirmed and further 219 probable cases were detected in Italy.
In 2010, France reported two cases of autochthonous CHIKV infection for the first time followed by autochthonous transmission events with 12 cases in 2014 and 17 cases in 2017, respectively.
In both countries CHIKV was transmitted through Ae. albopictus which is established in the region mainly during the summer months [4]. In two of the cases in this series, laboratory results showed acute viremia in PCR testing with the potential of autochthonous transmission in the presence of competent vectors. Hence, early diagnosis and surveillance of acute chikungunya infections in travelers are of public health concern as they have the potential to spread the virus to non-endemic areas.
After an incubation period of three to seven days, CHIKV causes a generally self-limiting illness with acute onset of high fever, severe arthralgia and maculopapular rash. Less common symptoms are fatigue, nausea, vomiting and conjunctivitis. Chikungunya is often mild and some infected individuals are asymptomatic but severe and lethal infections have been described [5]. The risk of severe disease is higher in infants, older persons, in persons with underlying medical conditions and in the immunocompromised. Chikungunya-related persistent or relapsing arthritis is described in up to 60% of patients and may last for months or even years [6].
All four cases we present in this series had prolonged arthralgia with the need for treatment with NSAIDs even though none had risk factors such as an underlying rheumatic disease or age older than 60 years.
At present, there is no specific treatment or vaccine available [6], even though vaccine candidates are under intense research. Travel medicine providers therefore must highlight the importance of mosquito-bite prevention such as the use of repellents containing 30–50% N,N-diethyl-meta-toluamide (DEET) and adequate clothing not only during the stay in the tropics but also upon return to home countries where Aedes spp. are present, as viremia may be present.
Although CHIKV is endemic in Indonesia, including Bali, where the prevalence acute CHIKV-infection was 3,7% in acutely hospitalized febrile patients in one study [7], acute chikungunya infection remains significantly underdiagnosed by clinicians, likely due to an overlap in clinical manifestations with other endemic infections such as cocirculating dengue virus infection, and the lack of diagnostic testing capacity. In the same study, 25,2%–45.9% of subjects showed serological evidence of prior CHIKV exposure [7].
This case series is meant to raise physicians’ awareness of possible CHIKV infection in travelers and in the local population. Since Bali is a popular tourist destination, the detection of imported CHIKV infections underlines the importance of travelers as infectious diseases sentinels.
Funding source
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Declaration of competing interest
The authors have declared no conflicts of interest.
Acknowledgements
None.
References
[1]
M.C. RobinsonAn epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952-53. I. Clinical featuresTrans R Soc Trop Med Hyg, 49 (1) (1955), pp. 28-32
View PDFView articleCrossRefView in ScopusGoogle Scholar
[2]
K. Sari, K.S.A. Myint, A.R. Andayani, P.D. Adi, R. Dhenni, A. Perkasa, et al.Chikungunya fever outbreak identified in North Bali, IndonesiaTrans R Soc Trop Med Hyg, 111 (7) (2017), pp. 325-327CrossRefView in ScopusGoogle Scholar
[3]
I.C. Sam, C.L. Chua, J.J. Rovie-Ryan, J.Y. Fu, C. Tong, F.T. Sitam, et al.Chikungunya virus in macaques, MalaysiaEmerg Infect Dis, 21 (9) (2015), pp. 1683-1685CrossRefView in ScopusGoogle Scholar
[4]
N.B. Tjaden, Y. Cheng, C. Beierkuhnlein, S.M. ThomasChikungunya beyond the tropics: where and when do we expect disease transmission in Europe?Viruses, 13 (6) (2021)Google Scholar
[5]
J.R. Torres, G. Leopoldo Codova, J.S. Castro, L. Rodriguez, V. Saravia, J. Arvelaez, et al.Chikungunya fever: atypical and lethal cases in the Western hemisphere: a Venezuelan experienceIDCases, 2 (1) (2015), pp. 6-10
View PDFView articleView in ScopusGoogle Scholar
[6]
R. Kumar, S. Ahmed, H.A. Parray, S. DasChikungunya and arthritis: an overviewTrav Med Infect Dis, 44 (2021), Article 102168
View PDFView articleView in ScopusGoogle Scholar
[7]
M. Arif, P. Tauran, H. Kosasih, N.M. Pelupessy, N. Sennang, R.H. Mubin, et al.Chikungunya in Indonesia: epidemiology and diagnostic challengesPLoS Neglected Trop Dis, 14 (6) (2020), Article e0008355CrossRefGoogle Scholar
EVENTS
FAQ
DOCUMENT LIBRARY (FOR MEMBERS)
Journal
Travel Medicine and Infectious Disease
DOI
https://doi.org/10.1016/j.tmaid.2023.102543
Abstract
Four cases of acute chikungunya virus infection (CHIKV) were reported among European citizens returning from Bali through the GeoSentinel Surveillance and Research Network. All travelers returned from Bali between May and June 2022.
The four cases reported, two male and two female, were aged between 24 and 37 years. One case was an expatriate and three were tourists. All four presented between March 27th and June 21st, 2022 to one of four GeoSentinel sites (Amsterdam, Barcelona, Munich and Paris) and had a probable or confirmed CHIKV infection with positive serum PCR, or a seroconversion with declining IgM and rising IgG in paired samples (Table 1). One case had a CHIKV infection diagnosed in Bali (unknown diagnostic method). No acute co-infection with dengue virus or Zika virus were reported in the three cases diagnosed at the GeoSentinel sites, but one case had false-positive Zika IgM which turned out negative upon repetition two weeks later. All four patients reported acute symptoms typical of chikungunya including fever, arthralgias and a rash. Three had a maculopapular rash and one an unspecified exanthema. Of note, all patients reported prolonged or recurrent arthralgias for which non-steroidal anti-inflammatory drugs (NSAIDs) were prescribed. In two cases, the infection was most probably acquired in Canggu in the south of the island, about 8 km west of Denpasar; in the other two cases the probable location could not be specified further.
Table 1. Epidemiological, clinical and diagnostic characteristics of confirmed and probable chikungunya cases in travelers from Bali presenting at GeoSentinel sites.
Case Age (Sex) Most probable place where infection was acquired Travel period (Date of symptom onset) Acute Symptoms Complications, treatment Chikungunya diagnostic method Additional arboviral diagnostic test results Outcome (Last date assessed)
1 24 (F) Canggu/Bali/Indonesia 04/05/2022–28/05/2022 (12/05/2022) Fever/generalized, pruritic maculopapular rash/arthralgias (bilateral small joints finger, wrist, knee, ankle) prolonged arthralgias (3 months), treatment with NSAIDs IgM 1:320 (<1:20)/IgG 1:160 (<1:20) (01/06/22) IgM 1:160 (<1:20)/IgG 1:320 (<1:20) (14/06/22) Dengue IgM (−)/IgG(+), NS 1 (−), PCR (−) Zika IgM(−)/IgG (−) full recovery (01/09/2022)
2 37 (M) Canggu/Bali/Indonesia Expatriate (27/03/2022) Fever, exanthema, generalized arthralgias prolonged arthralgias (5 months) with ankle swellings, treatment with NSAID Unknown (Diagnosis established in Bali)a Unknown full recovery (31/08/2022)
3 30 (M) Bali/Indonesia 06/06/2022–21/06/2022 (18/06/2022) Fever, maculopapular rash, arthralgia (bilateral: wrists), headache, lymphadenopathy (bilateral: latero-cervical, occipital, axillary and inguinal) prolonged arthralgia (>2 months) (wrists, metacarpophalangeal joints, knee), treatment with NSAIDs PCR (+), IgM(+)/IgG (−) (23/6/2022) IgM (+)/IgG(+) (07/07/2022) Dengue IgM-/IgG -, NS 1-, PCR (−) Zika PCR (−), IgM(+)/IgG(−) (23/06/22) Zika IgM(−)/IgG(−) (07/07/2022 full recovery (19/10/2022)
4 32 (F) Bali/Indonesia 06/06/2022–21/06/2022 (21/06/2022) Fever, generalized non-pruritic maculopapular rash, arthralgias (bilateral wrist, knee, ankle) relapsing and persistent arthralgias, treatment with NSAIDs PCR (+), IgM (−)/IgG (−) (23/06/22) CHIKV IgM (+)/IgG(+) (06/07/22) Dengue IgM(−)/IgG (−), NS 1(−) full recovery (21/09/2022)
a
According to the patient, the diagnosis was laboratory-confirmed on Bali; however, the patient did not carry written documentation with him when presenting for follow-up in Amsterdam.
Chikungunya virus is an alphavirus of the family Togaviridae, transmitted between humans through female Aedes spp. mosquitoes, especially Ae. aegypti and Ae. albopictus.
CHIKV was first identified during an outbreak in Tanzania in 1952 [1]. In the Asia-Pacific region, CHIKV was first reported from the Philippines in 1954, with subsequent outbreaks in various countries in southern and southeast Asia. The earliest report of chikungunya in Indonesia dates back to 1973. In the last two decades, outbreaks have been reported in several areas of Indonesia including Bali, in 2009–2011, and in Northern Bali in 2015–2016 [2].
In two of our reported cases, the most probable place CHIKV infection was acquired was Canggu. On the date of symptom onset, both patients were staying in Ubud, about 25 km north of Denpasar where Ubud Monkey Forest is a major tourist attraction. This shows how tourist mobility and labor flow is an important factor in local spread of infectious diseases. In addition, viremic visitors to Ubud Monkey Forest constitute a reverse zoonotic potential, that may affect the local long-tailed macaques (Macaca fascicularis) and create a CHIKV reservoir. Antibodies against CHIKV have been reported in long-tailed macaques from elsewhere in the region [3].
Another concern is the risk of autochthonous transmission of arboviruses by returning viremic travelers to non-endemic home countries where suitable mosquito vectors are present and very active during the summer period when the described case series took place.
In Europe, the first outbreak of autochthonous CHIKV infections was reported from Italy in 2007, after the virus was introduced by a traveler. More than 200 cases were reported in this outbreak. In 2017 the second cluster of autochthonous transmission of chikungunya virus with 270 confirmed and further 219 probable cases were detected in Italy.
In 2010, France reported two cases of autochthonous CHIKV infection for the first time followed by autochthonous transmission events with 12 cases in 2014 and 17 cases in 2017, respectively.
In both countries CHIKV was transmitted through Ae. albopictus which is established in the region mainly during the summer months [4]. In two of the cases in this series, laboratory results showed acute viremia in PCR testing with the potential of autochthonous transmission in the presence of competent vectors. Hence, early diagnosis and surveillance of acute chikungunya infections in travelers are of public health concern as they have the potential to spread the virus to non-endemic areas.
After an incubation period of three to seven days, CHIKV causes a generally self-limiting illness with acute onset of high fever, severe arthralgia and maculopapular rash. Less common symptoms are fatigue, nausea, vomiting and conjunctivitis. Chikungunya is often mild and some infected individuals are asymptomatic but severe and lethal infections have been described [5]. The risk of severe disease is higher in infants, older persons, in persons with underlying medical conditions and in the immunocompromised. Chikungunya-related persistent or relapsing arthritis is described in up to 60% of patients and may last for months or even years [6].
All four cases we present in this series had prolonged arthralgia with the need for treatment with NSAIDs even though none had risk factors such as an underlying rheumatic disease or age older than 60 years.
At present, there is no specific treatment or vaccine available [6], even though vaccine candidates are under intense research. Travel medicine providers therefore must highlight the importance of mosquito-bite prevention such as the use of repellents containing 30–50% N,N-diethyl-meta-toluamide (DEET) and adequate clothing not only during the stay in the tropics but also upon return to home countries where Aedes spp. are present, as viremia may be present.
Although CHIKV is endemic in Indonesia, including Bali, where the prevalence acute CHIKV-infection was 3,7% in acutely hospitalized febrile patients in one study [7], acute chikungunya infection remains significantly underdiagnosed by clinicians, likely due to an overlap in clinical manifestations with other endemic infections such as cocirculating dengue virus infection, and the lack of diagnostic testing capacity. In the same study, 25,2%–45.9% of subjects showed serological evidence of prior CHIKV exposure [7].
This case series is meant to raise physicians’ awareness of possible CHIKV infection in travelers and in the local population. Since Bali is a popular tourist destination, the detection of imported CHIKV infections underlines the importance of travelers as infectious diseases sentinels.
Funding source
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Declaration of competing interest
The authors have declared no conflicts of interest.
Acknowledgements
None.
References
[1]
M.C. RobinsonAn epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952-53. I. Clinical featuresTrans R Soc Trop Med Hyg, 49 (1) (1955), pp. 28-32
View PDFView articleCrossRefView in ScopusGoogle Scholar
[2]
K. Sari, K.S.A. Myint, A.R. Andayani, P.D. Adi, R. Dhenni, A. Perkasa, et al.Chikungunya fever outbreak identified in North Bali, IndonesiaTrans R Soc Trop Med Hyg, 111 (7) (2017), pp. 325-327CrossRefView in ScopusGoogle Scholar
[3]
I.C. Sam, C.L. Chua, J.J. Rovie-Ryan, J.Y. Fu, C. Tong, F.T. Sitam, et al.Chikungunya virus in macaques, MalaysiaEmerg Infect Dis, 21 (9) (2015), pp. 1683-1685CrossRefView in ScopusGoogle Scholar
[4]
N.B. Tjaden, Y. Cheng, C. Beierkuhnlein, S.M. ThomasChikungunya beyond the tropics: where and when do we expect disease transmission in Europe?Viruses, 13 (6) (2021)Google Scholar
[5]
J.R. Torres, G. Leopoldo Codova, J.S. Castro, L. Rodriguez, V. Saravia, J. Arvelaez, et al.Chikungunya fever: atypical and lethal cases in the Western hemisphere: a Venezuelan experienceIDCases, 2 (1) (2015), pp. 6-10
View PDFView articleView in ScopusGoogle Scholar
[6]
R. Kumar, S. Ahmed, H.A. Parray, S. DasChikungunya and arthritis: an overviewTrav Med Infect Dis, 44 (2021), Article 102168
View PDFView articleView in ScopusGoogle Scholar
[7]
M. Arif, P. Tauran, H. Kosasih, N.M. Pelupessy, N. Sennang, R.H. Mubin, et al.Chikungunya in Indonesia: epidemiology and diagnostic challengesPLoS Neglected Trop Dis, 14 (6) (2020), Article e0008355CrossRefGoogle Scholar