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Chikungunya InfectionAn Emerging Rheumatism Among Travelers Returned From Indian
Ocean Islands. Report of 47 CasesFabrice Simon, MD, Philippe Parola, MD, PhD, Marc Grandadam, PhD, Sabrina Fourcade, MD,
Manuela Oliver, MD, Philippe Brouqui, MD, PhD, Pierre Hance, MD, Philippe Kraemer, MD,
Anzime Ali Mohamed, MD, Xavier de Lamballerie, MD, PhD, Remi Charrel, MD, PhD,
and Hugues Tolou, MD, PhD
Abstract: A large chikungunya virus (CHIKV) outbreak emerged
in 20052006 in the Indian Ocean islands, including Comoros,
Mayotte, Mauritius, the Seychelles, and particularly in Reunion
Island where 35% of 770,000 inhabitants were infected in 6 months.
More recently, circulation of the virus has been documented inMadagascar and in India where CHIKV is spreading rapidly.
CHIKV-infected visitors have returned home to nonendemic
regions from these islands. We conducted a 14-month prospective
observational study on the clinical aspects of CHIKV infection
imported to Marseilles, France, in travelers returning from the
Indian Ocean islands. A total of 47 patients have been diagnosed
with imported CHIKV infection confirmed by serology, reverse
transcription-polymerase chain reaction, and/or viral culture. At the
early stage of the disease (within 10 days of the disease onset), fever
was present in 45 of 47 patients. A rash was present in the first week
in 25 cases. All patients suffered with arthritis. The most frequently
affected joints were fingers, wrists, toes, and ankles. Eight patients
were hospitalized during the acute stage, including 2 severe life-
threatening cases. A total of 38 patients remained symptomatic afterthe tenth day with chronic peripheral rheumatism, characterized by
severe joint pain and multiple tenosynovitis, with a dramatically
limited ability to ambulate and carry out activities in daily life.
Three patients were hospitalized at this stage for severe persistent
handicap. Follow-up demonstrated slow improvement in joint pain
and stiffness despite symptomatic treatment, mainly antiinflamma-
tory and analgesic drugs. In the current series we describe 2 stages
of the disease, an initial severe febrile and eruptive polyarthritis,
followed by disabling peripheral rheumatism that can persist for
months. We point out the possibility of transitory peripheral
vascular disorders during the second stage and the occasional
benefit of short-term corticosteroids. As CHIKV could spread
throughout the world, all physicians should be prepared to
encounter this arboviral infection.
(Medicine 2007;86:123137)
INTRODUCTION
M ore than 50 million people from industrialized westerncountries travel abroad and visit tropical developingcountries every year. About 8% of these travelers requiremedical care during or after travel, especially for commondiseases acquired while traveling as well as for infectious ortropical risks specifically related to the travel15,33.
Chikungunya virus (CHIKV) is an arbovirus (genus
Alphavirus, family Togaviridae) identified in the 1950s inAfrica, where it is maintained in a sylvatic cycle involvingwild primates and forest-dwelling mosquitoes35,38,39.CHIKV is also prevalent in Asian countries, where it has
been associated with Aedes aegypti, the main vector ofdengue fever, in an urban epidemiologic cycle without aknown animal reservoir29. There, the transmission has beensuspected to be supplemented by A. albopictus26.
The name chikungunya comes from the Makondelanguage of Tanzania and Mozambique, although it is oftenerroneously described as derived from Swahili, the mostwidely spoken language of eastern Africa5,28. The meaningthat which contorts or bends up, refers to the contorted
posture of infected patients suffering with severe joint pain
associated with the disease and a dramatic limited ability toambulate in daily life39. The disease has been rarelydescribed in the medical literature, and has long beenconsidered benign. Knowledge of its clinical features was
based until recently on the descriptions of South Africanteams after local epidemics in the late 1970s8,14,22. The acutestage includes brief fever, headache and myalgia, occasionalevanescent rash, and subacute bilateral and symmetricinflammatory polyarthralgia or arthritides that can last formonths. Brighton et al8 determined that 87.9% of 107serologically confirmed infected patients declared them-selves cured 3 years after disease onset, while 12.1%
Abbreviations: CHIKV = chikungunya virus, MRI = magneticresonance imaging, NSAIDs = nonsteroidal antiinflammatory drugs,RT-PCR = reverse transcription-polymerase chain reaction.
Medicine Volume 86, Number 3, May 2007 123
From Service de Pathologie Infectieuse et Tropicale (FS, SF, PK, AAM)and Laboratoires de Biologie et de Biochimie (MO, PH), HopitaldInstruction des Armees Laveran; Service des Maladies Infectieuses etTropicales (PP, PB), Hopital Nord, AP-HM, IFR48; Laboratoire deVirologie (MG, HT), IMTSSA; and Unite des Virus Emergents (XDL,RC), Faculte de Medecine Marseilles, France.
This work was supported by Direction Genede la Sante and Service de Santedes Armees.
Address reprint requests to: Dr. Fabrice Simon. Service de PathologieInfectieuse et Tropicale. Hopital dInstruction des Armees Laveran. BP50. 13998 Marseilles Armees, France. Fax: 33(0)4 91 61 75 04; e-mail:[email protected].
Copyright n 2007 by Lippincott Williams & WilkinsISSN: 0025-7974/07/8603-0123DOI: 10.1097/MD.0b013e31806010a5
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mentioned persistent symptoms including occasional dis-comfort, persistent joint stiffness, or stiffness and pain andeffusion (3.7%, 2.8%, and 6% respectively). Brighton andcolleagues9 also reported a case of late articular destructionafter decades of post-CHIKV chronic rheumatism, but didnot attribute direct cause to the virus.
Since 1952, CHIKV has caused outbreaks in EastAfrica (Tanzania and Uganda), in Austral Africa (Zimbabweand South Africa), in West Africa (Senegal and Nigeria),and in Central Africa (Central African Republic andDemocratic Republic of the Congo). In 19992000, a re-emergence was documented in the Democratic Republic ofthe Congo, where an estimated 50,000 persons wereinfected during an urban epidemic after 39 years withoutany isolation of the virus35. Serosurveys conducted inCameroon have suggested that interepidemic infection isalso common24. In Asia, since the first documented outbreak
in 1958 in Thailand, other outbreaks have been documentedin Thailand, Cambodia, Vietnam, Laos, Burma (Myanmar),Malaysia, the Philippines, and Indonesia25,29. The mostrecent epidemic re-emergence was documented in 20012003 in Indonesia, after a near 20-year hiatus of epidemicCHIKV activity in the country26. Both in Africa and Asia,CHIKV is characterized by the potential for major epidemicsthat re-emerge after an unpredictable period of apparentabsence.
At the beginning of 2005, an outbreak of CHIKV feveremerged in the southwestern islands of the Indian Ocean4,13.More than 5000 cases were reported in Comoros Islands, andthereafter the virus has circulated in other islands includingReunion and Mayotte (2 French territories), Mauritius, and
the Seychelles12,20,42
. At the beginning of 2006, after aperiod of lower transmission during the winter and with thearrival of the Southern Hemisphere summer, Reunion Islandsuffered an explosive outbreak. By September 18, 2006, anestimate of 266,000 residents (population 770,000) infectedwith CHIKV was reported, and 248 death certificates gaveCHIKV as the possible cause of death21. Evidence forintrauterine infection in pregnant women and verticaltransmission has been documented27. A. albopictus is theincriminated local vector2,37. More recently, circulation ofthe virus has also been documented in Madagascar and inIndia where CHIKV is spreading rapidly with more than
1,100,000 cases reported by the health authorities sinceDecember 2005, including 101,500 laboratory-confirmedcases20,49. Recently, the virus responsible for the massiveoutbreak in the Indian Ocean islands and India has beencharacterized, indicating that the outbreak was initiated by avirus related to East African CHIKV isolates, from whichnew variants may have evolved31,40,49.
According to the World Organization of Tourism,719,000 tourists arrived in Mauritius, 430,000 in ReunionIsland, 229,000 in Madagascar, and 121,000 in theSeychelles in 200448. During 20052006 several Europeancountries reported imported cases in travelers returning fromthese islands, including to mainland France (808 importedcases from April 2005 to August 2006)19,23, where viremic
patients have been diagnosed31; Germany, Italy, Norway,and Switzerland2. Recently cases have also been imported inthe United States10.
We describe here the clinical and laboratory features oftravelers with CHIKV infection diagnosed in Marseilles,France, returning from the Indian Ocean islands.
PATIENTS AND METHODSPatients with suspected travel-acquired CHIKV infec-
tion were prospectively recorded between February 2005 andApril 2006 in the infectious and tropical diseases units inMarseilles, located at the Laveran Hospital, a 300-bedmilitary hospital where civilians are also admitted, and at the
North Hospital, an 800-bed university-affiliated teachinghospital. Both units are reference centers for tropical diseasesand travel-related illnesses in southern France and include an
outpatient clinic. CHIKV infection was suspected in allpatients who returned from Indian Ocean islands whocomplained of fever and/or arthralgia. The case definitionwas as follows: 1) a history of travel to an island in thewestern Indian Ocean, 2) positive serologic results defined asthe presence of specific IgM or both IgM and IgG againstCHIKV, and/or positive reverse transcription-polymerasechain reaction (RT-PCR) and/or isolation of CHIKV from
blood, 3) no other etiology identified. In-house IgM-captureand IgG-capture enzyme-linked immunosorbent assays35 aswell as immunofluorescence assay using CHIKV (Rossstrain)-infected Vero cells were used to detect specific IgG
FIGURE 1. Incidence of CHIKV-infected travelers returning from Indian Ocean islands to Marseilles, France, March 2005 to April2006.
124 n 2007 Lippincott Williams & Wilkins
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and IgM31. RT-PCR and isolation in Vero-E6 cells ofCHIKV from acute sera, were also attempted as describedelsewhere31,34. Descriptions of demographic, clinical, andlaboratory findings of both acute and chronic stages wereregistered for all patients at the first consultation and/or atthe time of hospitalization and during follow-up. For patientsseen more than 10 days after the onset of illness, clinicalfeatures of the early stage of the disease were identified byretrospective questioning. After the initial consultation or
hospitalization, patients status was actively followed byregular consultations and/or phone calls until October 2006.
RESULTS
Demographic and Epidemiologic FeaturesA total of 47 patients with confirmed imported CHIKV
infection were identified (39 at the Laveran Hospital and 8 atthe North Hospital). The mean age was 45.1 years (range,0.573 yr), with 22 female patients and 25 males (Table 1).Places of infection and times of the first hospital consultationare presented in Figure 1. The 47 patients comprised the
following: 1) 29 individuals permanently residing inmetropolitan France who traveled for tourism, 2) 10 migrantsof Comorian origin living in metropolitan France (including2 pregnant woman) who traveled to visit friends andrelatives, 3) 7 residents of an Indian Ocean island whotraveled to metropolitan France, and 4) a 5-month-oldCanadian child whose family stopped for a few days inFrance after visiting Reunion Island before returning toCanada. The length of stay in Indian Ocean islands,
excluding residents of Reunion Island, ranged from 9 to180 days (mean, 3.1 mo). Underlying conditions werepresent in 30 infected patients (see Table 1). The diseasedeveloped in 26 patients during travel and in 21, on theirreturn. The mean interval between return and first symptomswas 2.4 days (range, 07 d).
Clinical and Laboratory Features at the EarlyStage of CHIKV Infection
Twelve patients presented in Marseilles during theearly stage (within 10 d of the disease onset), and 8 werehospitalized. The reason for hospitalization was a febrile
FIGURE 2. Skin manifestations in patients with CHIKV infection returning from Reunion Island to Marseilles in 2006, including a
45-year-old woman with rash of the face (A) and abdomen (B) and edema of the face (A) and hand (C); and a 36-year-old manwith rash that blanches with pressure on the right arm (D, E).
n 2007 Lippincott Williams & Wilkins 125
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TABLE
1.DemographicandMedicalDataof47PatientsWithTravel-AcquiredChikungunyaInfection,Marseilles,France,March2005April200
6
Patient
Sex/age
(yr)
MainUn
derlying
Con
dition
Locationof
Infection
Lengthof
Stay(d)
Departure-
Disease
Onset
Delay(d)*
Placeof
Disease
Onset
Disease
Onset
First
Specialized
Consultation
Stageat
First
Consultation
y
Hospitalization
1
M/25
Type2diab
etes
Comoros
Resident
300
Comoros
1/1/2005
1/27/2006
2
2
M/45
Comoros
135
30
Comoros
3/1/2005
6/17/2005
2
3
F/41
2-month
pregnancy
Comoros
270
45
Comoros
3/13/2005
4/26/2005
2
4
M/29
Comoros
180
6
Mainland
France
3/13/2005
3/21/2005
1
+(st.1)
5
F/39
Comoros
45
3
Mainland
France
3/17/2005
4/19/2005
2
6
M/61
type2diabetes,
malaria,
synovialcysts
Comoros
Resident
20
Comoros
3/18/2005
4/12/2005
2
7
F/56
Hypertensio
n
Comoros
30
6
Mainland
France
4/3/2005
4/13/2005
1
8
M/35
Comoros
21
4
Comoros
4/7/2005
4/20/2005
2
9
M/61
Ligamentop
lasty
ofonekn
ee,
malaria
Reunion
Resident
70
Reunion
4/23/2005
7/1/2005
2
10
F/61
Chroniclum
bar
painand
sciatica
Reunion
Resident
70
Reunion
4/23/2005
7/1/2005
2
11
M/40
Malaria
Comoros
40
4
Comoros
4/24/2005
3/28/2005
1
+(st.1)
12
M/27
Achondroplasia
Mayotte
Resident
0
Mainland
France
12/1/2005
3/10/2006
2
13
F/34
2-monthpre
gnancy
Seychelles
26
18
Seychelles
12/18/200
5
3/10/2006
2
14
F/55
Hiposteoarthritis,
osteoporo
sis
Reunion
15
6
Reunion
1/7/2006
3/6/2006
2
15
F/30
Forearmfra
cture
Reunion
23
22
Reunion
1/12/2006
3/24/2006
2
16
F/36
Reunion
45
0
Mainland
France
1/13/2006
2/12/2006
2
17
F/55
Gastriculce
r,
aspirinallergy
Reunion
12
7
Reunion
1/14/2006
2/13/2006
2
18
F/28
Reunion
34
3
Mainland
France
1/14/2006
2/21/2006
2
19
M/26
Reunion
43
9
Reunion
1/15/2006
4/19/2006
2
20
F/21
Obesity,gastric
ulcer
Reunion
39
1
Reunion
1/18/2006
4/13/2006
2
+(st.1)
21
F/55
Hypertensio
n,
deepveno
us
thrombosis
Reunion
14
1
Mainland
France
1/26/2006
3/1/2006
1
22
M/22
Reunion
29
1
Mainland
France
1/28/2006
4/11/2006
2
+(st.1)
23
F/31
Reunion
30
1
Mainland
France
1/28/2006
2/27/2006
2
126 n 2007 Lippincott Williams & Wilkins
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24
M/61
Hypertensio
n,
type2
diabetes
Reunion
Resident
25
Reunion
2/1/2006
3/17/2006
2
25
F/31
Comoros
NA
2
Mainland
France
2/2/2006
3/2/2006
1
+(st.1)
26
F/65
Metastaticb
reast
cancer,ps
oriatic
arthritis
Reunion
39
9
Reunion
2/3/2006
3/3/2006
2
27
M/65
Chroniclum
barpain
andsciatica
Reunion
90
18
Reunion
2/4/2006
3/30/2006
2
28
F/55
Breastcancer,
ovariancancer,
hypertension
Reunion
11
40
Reunion
2/5/2006
3/16/2006
2
29
F/62
Angioedema,chronic
gastritis,
cervicobrachial
neuralgia,rheumatic
feverinchildhood
Reunion
105
41
Reunion
2/8/2006
3/7/2006
2
+(st.2)
30
M/62
Post-traumatichip
osteoarthr
itis,
coronarop
athy,
deepveno
us
thrombosis,
Dupuytrendisease
Reunion
105
40
Reunion
2/9/2006
3/7/2006
2
+(st.2)
31
M/48
Diverticular
disease,
shoulderinjury,
severehypertension
Reunion
9
1
Mainland
France
2/10/2006
2/16/2006
1
32
F/47
Multipleten
donitis
andarthro
sis
Reunion
36
1
Mainland
France
2/10/2006
2/16/2006
1
33
M/73
Metastaticintestinal
sromaltumortreated
withimatinib,type
2diabetes
Reunion
60
NA
Mainland
France
2/14/2006
7/18/2006
1
+(st.1)
34
F/65
Meniscetom
yofone
knee,severe
hypertension
Reunion
49
1
Mainland
France
2/18/2006
3/29/2006
2
+(st.2)
35
M/65
Type2diab
etes,
hypertension,
Dupuytrendisease
Reunion
49
1
Mainland
France
2/18/2006
3/29/2006
2
36
M/32
Reunion
13
5
Reunion
2/21/2006
2/28/2006
1
37
M/5mo
Reunion
10
3
Mainland
France
2/22/2006
2/24/2006
1
+(st.1)
38
M/45
Mauritius
17
3
Mauritius
2/22/2006
NA
NA
(contin
uedonnextpage)
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TABLE
1.
(continued)
Patient
Sex/age
(yr)
MainU
nderlying
Co
ndition
Locationof
Infection
Lengthof
Stay(d)
Departure-
Disease
Onset
Delay(d)*
Placeof
Disease
Onset
Disease
On
set
First
Specialized
Consultation
Stageat
First
Consultation
yH
ospitalization
39
M/78
Type2diabetes,
hypertension,
cardia
cfailure,
Dupuytren
diseas
e
Mauritius
51
1
Mainland
France
2/23/2006
4/25/2006
2
+(st.1)
40
M/57
Obesity,cardiac
failure,
sleepapnea,
hypertension,
Dupuytren
diseas
e
Reunion
45
1
Reunion
2/25/2006
4/21/2006
2
41
F/38
Reunion
Resident
9
Reunion
2/26/2006
4/13/2006
2
42
M/37
Injuryofthe
righthemib
dody
10yr
before
Reunion
30
14
Reunion
2/26/2006
4/3/2006
2
43
F/63
Hypothy
roidism,
multip
le
tendonitis
Reunion
90
19
Reunion
2/28/2006
3/23/2006
2
44
F/42
Mauritius
14
6
Mainland
France
3/4/2006
3/7/2006
1
45
M/31
Reunion
22
1
Mainland
France
3/13/2006
3/13/2006
1
46
M/57
Psoriasis
Reunion
30
0
Mainland
France
3/15/2006
3/21/2006
2
47
M/25
Reunion
9
3
Mainland
France
3/15/2006
4/4/2006
2
Total
M/F:1.14
st.1:12,
st.2:34
11/47
Meanage:
45.1y,(range:
0.5to73y)
30/47,includ
ing
2preg
nant
wome
n
Reunion:32,
Comoros
andMayotte:11,
Mauritius
andSeychelles:4M
ean:3.1mo
(residents
excepted)
Mean:17d
(range:
300to6d)
Mainland
France:
21Islands
ofwestern
IndianOcean:26
*Negativevaluewhendiseaseonsetbeforereturn.
yStage150% and anestimated 13,500 persons infected3. Cases were then de-scribed in Mombasa, beginning in November 2004. At first,after having excluded malaria, this disease outbreak wassuspected to be due to onyong-nyong fever virus, anothermember of the genusAlphavirus(PROMED Archive Number20041214.331; http://www.promedmail.org). Recent molec-ular analysis has confirmed that it was caused by CHIKV6,however, and may have been the beginning of the subsequentmassive outbreak in the Indian Ocean5. Furthermore, denguevirus is endemic in many of the same tropical locations where
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TABLE
3.ClinicalFeaturesof47Patient
satFirstStageofTravel-AcquiredChikungunyaInfection,Marseilles,France,March2005-April2
006
Patient
ChronicJoint
Painand/or
Stiffness
Hand
and/or
Feet
Involvement
Symmetry
ofJoint
Involvement
Exacerbation
ofPre-existing
Pains
Axial
Involvement
Tenosynovitis/
Ten
donitis
(lo
cation)
Nervous
Tunnel
Syndrome
Peripheral
Vascular
Disorder
(period)
Oth
er
Significant
Events
Follow-up
After
Disease
Onset(mo)
Lostto
Follow-Up
Short-term
General
Corticotherapy
(No.)
Clinical
Outcome
(timeafter
diseaseonset)
1
+
+
+
+
13
+
Stillpainful
after13mo
2
+
+
12
Cureat4mo
3
+
+
+
+(Wrx2)
Raynaudsd
(6th-9thmo)
Normal
Pregnancy
andChild
Grow
th
17
+(1time)
Cureat15mo
4
NA
NA
NA
NA
NA
NA
NA
NA
NA
Nocontact
after1st
CS
+
NA
NA
5
+
+
+
19
Cureat4mo
6
+
+
+
+(Shx2)
16
Cureat4mo
7
+
+
+
18
+(1time)
Cureat2mo
8
+
+
+
+(Anx2)
+(Cax1)
19
Cureat14mo
9
+
+
+
+(Ce)
+(Wrx2)
+(Cax2)
5
+
+(1time)
Stillpainful
after5mo
10
+
+
+
+(Wrx2)
+(Cux1)
5
+
+(1time)
Stillpainful
after5mo
11
+
+
+
Nocontact
after2mo
+
Stillpainful
after2mo
12
+
+
+
+(Ce)
11
Cureafter7mo
13
+
+
+
+(Fi,To)
Unknow
n
pregnancy
outcome
Nocontact
after1st
CS
+
NA
14
+
+
4
+
Stillpainful
after4mo
15
+(Elhygromas)
+
+
+(Ce,Lu)
+(Wrx2,Fi)
Raynaudsd
(2nd-3rdmo),
prolonged
handredness
Depression
Nocontact
after1st
CS
+
Stillpainful
after3mo
16
+
+
+
+(Ce,Lu)
+(W
rx2,
Fi,Anx2)
Raynaud
sd(3rdm)
1brief
relapse
at5thmo
9
+(1time)
Stillpainful
after9mo
17
+
+
+(spine)
+(Ce,Do)
+(Cax1)
8
Stillpainful
after8mo
18
+
+
+
+(Lu)
+(Wrx2,Fi)
Erythermalgia
(2nd-3rdmo)
6
+(1time)
Stillpainful
after6mo
19
+
+
+(W
rx1,
Achilles
tendon)
9
Stillpainful
after9mo
20
+
+
+
+(Ce,Lu)
+
+(Cax2,
Tax2l)
9
Cureat7mo
21
+
+
+
+(Ce)
+(W
rx2,
Fi,Anx2)
+(Cax1)Erythermalgia
(2ndmo)
7
+(1time)
Cureat6mo
22
9
Cureat10d
23
+
+
+
+(Ce)
9
Cureat4mo
24
+
+
+
+(Wrx2)
+(Cax2)Raynaudsd
(2nd-3rdmo),
prolonged
handredness
5
+(2times)
Stillpainful
after5mo
134 n 2007 Lippincott Williams & Wilkins
Simon et al Medicine Volume 86, Number 3, May 2007
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25
+
+
+
+(Wrx2)
NA
2
+
Stillpainful
after2mo
26
+
+
+(spine,
tibia,
femur)
+(Lu)
Concom
itant
spreading
ofbone
meta
stases
8
+(1time)
Cureat3mo
27
+
+
+
+(TeMax2)
+(Fi,To)
1digital
pulpnecrosis
whenskiing
(2ndmo)
1relapseaf
ter
moxiflox
acin
givenfor
bronchitis;
transitory
depressio
n
Nocontact
after1st
CS
+
+(1time)
NA
28
+
+
+
+
+(Ce,TeMa)+(Anx2)
1relapse
8
+
+(2times)
Cureat5mo
29
+
+
+
+(spine)
+(Ce,Do)
+(W
rx2,
Fi,Anx2)
+(Cax2)fingercoldness
(2nd-3rdmo)
3relapses
8
+(2times)
Stillpainful
after8mo
30
+
+
+
+(hip)
+(Wrx2,Fi)
3relapses;
hipreplacement
forpainful
osteoarth
ritis
in2006/06
8
+(3times)
Stillpainful
after8mo
31
NA
NA
NA
NA
NA
NA
NA
NA
NA
Nocontact
after1st
CS
+
NA
NA
32
+(Kneffusion
x2)
+
+
+(spine)
+(Ce,Sc)
+(W
rx2,
Fi,Anx2)
+(Cax2)
2
+
+(1time)
NA
33
+
+
+
+(Wrx1,Fi)
8
Symtom-free
after6mo
34
+
+
+
+(W
rx2,
Fi,Anx2)
7
+(1time)
Cureat4mo
35
+
+
+
+(Wrx1,Fi)
5
Cureat4mo
36
1
+
Cureat1mo
37
NA
NA
NA
NA
NA
NA
NA
NA
NA
Nocontactat
1st
CS
+
NA
NA
38
1m
+
Cureat1mo
39
+
+
+
+(W
rx2,
Fi,Anx2)
2relapses;
transitory
thoughts
ofsuicide
7
+(2times)
Stillpainful
after7mo
40
+
+
+
+(hips)
+(W
rx2,
Fi,To)
Raynaudsd
(3rdm)
8
+(2times)
Stillpainful
after8mo
41
+
+
+
+
+(Cax1)
8
Cureat3mo
42
+
+
+(W
rx1,
El
x1,To)
7
+(1time)
Cureat6mo
43
+
+
+
+
+(Sc)
+(W
rx2,Fi,
An
x2,To,
Kn
,Shx1)
+(Cax1,
Tax1)
7
+(1time)
Stillpainful
after7mo
44
1
+
Cureat1mo
45
Nocontact
after1st
CS
+
NA
46
8
Cureat10d
47
+
+
+
+(Wrx2,Fi)
6
Cureat4mo
Total
38/44
37/44
33/44
9/44
16/44
2
6/44
11/44
9/43
6patientsw
ith
relapses
Mean=8mo
18/47
19/44
Abbreviations:Seeprevioustables.Ca
=carpal,Cu=cubital,Ta=tarsal,CS=consultatio
n.
n 2007 Lippincott Williams & Wilkins 135
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CHIKV epidemics have occurred, and usually overshadowsCHIKV and other arboviral diseases. In the description ofthe disease by Robinson38 in 1955, proposed clinicalfindings that would improve the differential diagnosis ofother febrile outbreaks with arthralgia and were more
characteristic of CHIKV infection were the absence ofadenopathy, the frequent dissociation of the rash and thesecondary rise of the temperature, the lack of post-orbital
pain, or pain on moving the eyes, and the long continuanceof chronic joint pains. The data presented here, particu-larly the 2-phased disease evolution, the presence ofmultiple tenosynovitis, a typical pain on pressure to thewrists, and the delayed onset of Raynaud syndrome mayalso be helpful in diagnosis.
To date, treatment of CHIKV infection is still solelysymptomatic against fever, pain, and handicap. During theacute stage, patients improved with paracetamol, analgesics,short-term systemic NSAIDs, or corticotherapy. Neverthe-less, physicians must be aware of possible severe adverse
effects such as aspirin-induced bleeding or paracetamol-induced fulminant hepatitis in patients with underlyingchronic liver disease20. The management of chronic CHIKVrheumatism is based on analgesics, local and/or systemic
NSAIDs, and physiotherapy. When NSAIDs are contra-indicated or local treatment fail, short-term systemic cortico-therapy is of interest and can lead to dramatic improvement,although a few patients experienced a painful relapse a fewdays after discontinuation.
In our experience, the management of the elderlyinfected travelers was more difficult because they hadcomorbidity and experienced more severe pain and handicap,as previously noticed by Brighton et al8,14,22, and sometimes
depressive disorders. Most patients with tenosynovitis werepoorly responsive to NSAIDs but dramatically improved aftershort-term systemic corticosteroids. Although some patientsexperienced relapses during the second stage requiring repeatshort-term corticotherapy, we did not experience steroid-dependent CHIKV-associated rheumatism. In order to treatchronic CHIKV-associated rheumatism, Brighton7 conductedan open pilot study with chloroquine phosphate, in which 5 of10 treated patients had significant improvement of Ritchiearticular index and morning stiffness after a 20-week therapy.The single patient of the current study who initially received a14-day chloroquine treatment improved in locomotion, but
became symptom-free only after 6 months. Controlled studiesare being conducted in Reunion to evaluate the efficacy of
early chloroquine treatment in CHIKV infection (de Lamball-erie, personal data).
In conclusion, the current series of CHIKV amongtravelers describes some new aspects of the 2-phasedarboviral disease characterized by a severe febrile anderuptive polyarthritis, commonly followed by persistinghandicapping peripheral rheumatism. Some life-threateningmanifestations and unusual rheumatic symptoms (tenosyno-vitis, Raynaud syndrome) were also observed. CHIKV,which was classically located in Africa and in SoutheastAsia, is now spreading to new territories in the western andeastern Indian Ocean and India11. CHIKV infection has now
to be considered in the diagnosis in patients who live in orare traveling to and from endemic or epidemic regions.Furthermore, although A. albopictus, the Asian tigermosquito, was implicated as the vector in Reunion, and isindigenous to Southeast Asia, the western Pacific and the
Indian Oceans, it has recently spread to Africa, the MiddleEast, Europe, and the Americas, mainly because oftransportation of dormant eggs in tires17. In some Mediter-ranean countries, such as Italy,A. albopictus is highly activeduring the summer17,45. Thus, emergence of autochthonousCHIKV is theoretically possible when coexistence of viremic
patients and competent vectors occurs. Finally, nosocomialtransmission has been documented in southern France, in anurse who had direct contact with the blood of a viremic
patient31. Considering all these recent data, CHIKV is anarboviral disease that all physicians should be prepared toencounter.
ACKNOWLEDGMENTSWe are grateful to Dr. Marimoutou for statisticalsupport and to Drs. Lin Chen and Paul Newton for editingand helpful comments.
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