4.- chikungunya infection an emerging rheumatism among travelers returned from indian.pdf

8/10/2019 4.- CHIKUNGUNYA INFECTION AN EMERGING RHEUMATISM AMONG TRAVELERS RETURNED FROM INDIAN.pdf

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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

Copyr ight Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.


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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

Simon et al Medicine Volume 86, Number 3, May 2007



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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

Medicine Volume 86, Number 3, May 2007 Emerging Chikungunya Infection



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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





5/15

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





13/15

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.





14/15

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.

REFERENCES

1. Anonymous. Chikungunya fever among U.S. Peace Corps VolunteersRepublic of the Philippines. MMWR Morb Mortal Wkly Rep. 1986;36:573574.

2. Anonymous. Outbreak news. Chikungunya and dengue, south-westIndian Ocean. Wkly Epidemiol Rec. 2006;81:106108.

3. Bedno S, Onyango C, Njuguna C, Sang R, Gaydos S, Sergon K, et al.Outbreak of chikungunya in Lamu, Kenya, 2004. Fifth InternationalConference on Emerging Infectious Diseases 2006; Atlanta, GA, USA,March 1922, 2006. Available at: http://www.cdc.gov/iceid/ (accessed

October 2006).4. Bodenmann P, Genton B. Chikungunya: an epidemic in real time.

Lancet. 2006;368:258.5. Bonn D. How did chikungunya reach the Indian Ocean? Lancet Infect

Dis. 2006;6:543.6. Breiman R, Sergon K, Sang R, Burke H, Bedno S, Njuguna C, et al.

Rapid re-emergence of chikungunya virus in East Africa. FifthInternational Conference on Emerging Infectious Diseases 2006;Atlanta, GA, USA, March 1922, 2006. Available at: http://www.cdc.gov/iceid/ (accessed October 2006).

7. Brighton SW. Chloroquine phosphate treatment of chronic chikungunyaarthritis.S Afr Med J. 1984;11:217218.

8. Brighton SW, Prozesky OW, De La Harpe AL. Chikungunya virusinfection: a retrospective study of 107 cases.S A Med J. 1983;63:313315.

9. Brighton SW, Simson IW. A destructive arthropathy followingchikungunya virus arthritisa possible association. Clin Rheumatol.1984;3:253258.

10. Centers for Disease Control and Prevention (CDC). Chikungunya feverdiagnosed among international travelersUnited States, 20052006.

MMWR Morb Mortal Wkly Rep. 2006;55:10401042.11. Charrel RN, de Lamballerie X, Raoult D. Chikungunya outbreaks

the globalization of vectorborne diseases. N Engl J Med. 2007;356:769771.

12. Cordel H. Chikungunya outbreak on Reunion: update. http://www.eurosurveillance.org/ew/2006/060302.asp#3 (accessed March 3, 2006).

13. Enserink M. Massive outbreak draws fresh attention to little-knownvirus.Science. 2006;311:1085.

14. Fourie ED, Morrison JGL. Rheumatoid arthritic syndrome afterchikungunya fever. S A Med J. 1979;56:130132.

15. Freedman DO, Weld LH, Kozarsky PE, Fisk T, Robins R, von SonnenburgF, Keystone JS, PandeyP, Cetron MS; GeoSentinel Surveillance Network.





15/15

Spectrum of disease and relation to place of exposure among ill returnedtravelers. N Engl J Med. 2006;354:119130.

16. Gould EA, Higgs S, Buckley A, Gritsun TS. Potential arbovirusemergence and implications for the United Kingdom. Emerg Infect Dis.2006;12:549555.

17. Gratz NG. Critical review of the vector status of Aedes albopictus.MedVet Entomol. 2004;18:215227.

18. Hochedez P, Jaureguiberry S, Debruyne M, Bossi P, Hausfater P,Brucker G, Bricaire F, Caumes E. Chikungunya infection in travelers.

Emerg Infect Dis. 2006;12:15651567.19. Institut National de Veille Sanitaire. [Chikungunya cases imported to

France from April 2005 to August 2006. Update on September27th]. Available at: http://www.invs.sante.fr/presse/2006/le_point_sur/chikungunya_cas_importes_270906/chikungunya_ cas _importes_270906.pdf (accessed October 1, 2006).

20. Institut National de Veille Sanitaire. [Chikungunya outbreak on ReunionIsland and in Indian Ocean: update on September 18th]. Available at:http://www.invs.sante.fr/surveillance/chikungunya/default.htm (accessedOctober 1, 2006).

21. Institut National de Veille Sanitaire. [Chikungunya outbreak onReunion: update on September 18th, 2006]. Available at: http://www.invs.sante.fr/presse/2006/le_point_sur/chikungunya_reunion_280906/chikungunya_reunion_s38.pdf (accessed October 1, 2006).

22. Kennedy AC, Fleming J, Solomon L. Chikungunya viral arthropathy: aclinical description. J Rheumatol. 1980;7:231236.23. Krastinova E, Quatresous I, Tarantola A. Imported cases of chikungunya

in metropolitan France: update to June 2006. Euro Surveill. 2006;11:E060824.1.

24. Kuniholm MH, Wolfe ND, Huang CY, Mpoudi-Ngole E, Tamoufe U,LeBreton M, Burke DS, Gubler DJ. Seroprevalence and distribution ofFlaviviridae, Togaviridae, and Bunyaviridae arboviral infections in ruralCameroonian adults. Am J Trop Med Hyg. 2006;74:10781083.

25. Lam SK, Chua KB, Hooi PS, Rahimah MA, Kumari S, TharmaratnamM, Chuah SK, Smith DW, Sampson IA. Chikungunya infectionanemerging disease in Malaysia. Southeast Asian J Trop Med Public

Health. 2001;32:447451.26. Laras K, Sukri NC, Larasati RP, Bangs MJ, Kosim R, Djauzi R, Wandra

T, Master J, Kosasih H, Hartati S, Beckett C, Sedyaningsih ER, BeechamHJ III, Corwin AL. Tracking the re-emergence of epidemic chikungunyavirus in Indonesia.Trans R Soc Trop Med Hyg. 2005;99:128141.

27. Lenglet Y, Barau G, Robillard PY, Randrianaivo H, Michault A,Bouveret A, Gerardin P, Boumahni B, Touret Y, Kauffmann E,Schuffenecker I, Gabriele M, Fourmaintraux A. [Chikungunya infectionin pregnancy: evidence for intrauterine infection in pregnant women andvertical transmission in the parturient. Survey of the Reunion Islandoutbreak.].J Gynecol Obstet Biol Reprod (Paris). 2006;35:578583.

28. Lumsden WHR. An epidemic of virus disease in southern province,Tanganyika territory, in 19521953. II. General description andepidemiology.Trans R Soc Trop Med Hyg. 1955;49:3357.

29. Mackenzie JS, Chua KB, Daniels PW, Eaton BT, Field HE, Hall RA,Halpin K, Johansen CA, Kirkland PD, Lam SK, McMinn P, Nisbet DJ,Paru R, Pyke AT, Ritchie SA, Siba P, Smith DW, Smith GA, van denHurk AF, Wang LF, Williams DT. Emerging viral diseases ofSoutheast Asia and the Western Pacific. Emerg Infect Dis. 2001;7(3 Suppl):497504.

30. Mourya DT, Mishra AC. Chikungunya fever. Lancet. 2006;368:186187.

31. Parola P, de Lamballerie X, Jourdan J, Rovery C, Vaillant V, Minodier P,Brouqui P, Flahault A, Raoult D, Charrel RN. Novel chikungunya virus

variant in travelers returning from Indian Ocean islands. Emerg InfectDis. 2006;12:14931499.

32. Parola P, Gazin P, Pradines B, Parzy D, Delmont J, Brouqui P.Marseilles: a surveillance site for malaria from Comoros Islands.

J Travel Med. 2004;11:184186.33. Parola P, Soula G, Gazin P, Foucault C, Delmont J, Brouqui P. Fever in

travelers returning from tropical areas: prospective observational studyof 613 cases hospitalised in Marseilles, France, 19992003. Trav Med

Inf Dis. 2006;4:6170.34. Pastorino B, Bessaud M, Grandadam M, Murri S, Tolou HJ, Peyrefitte

CN. Development of a TaqMan RT-PCR assay without RNA extractionstep for the detection and quantification of African chikungunya viruses.

J Virol Methods. 2005;124:6571.35. Pastorino B, Muyembe-Tamfum JJ, Bessaud M, Tock F, Tolou H,

Durand JP, Peyrefitte CN. Epidemic resurgence of chikungunya virus inDemocratic Republic of the Congo: identification of a new centralAfrican strain. J Med Virol. 2004;74:277282.

36. Pile JC, Henchal EA, Christopher GW, Steele KE, Pavlin JA.Chikungunyain a NorthAmerican traveler. J TravelMed. 1999;6:137139.

37. Reiter P, Fontenille D, Paupy C. Aedes albopictus as an epidemic vectorof chikungunya virus: another emerging problem? Lancet Infect Dis.2006;6:463464.

38. Robinson MC. An epidemic of virus disease in Southern Province,

Tanganyika Territory, in 195253. I. Clinical features.Trans R Soc TropMed Hyg. 1955;49:2832.39. Ross W. The Newala epidemic. III. The virus: isolation, pathogenic

properties and relationship to the epidemic. J Hyg (Lond). 1956;54:177191.

40. Schuffenecker I, Iteman I, Michault A, Murri S, Frangeul L, Vaney MC,Lavenir R, Pardigon N, Reynes JM, Pettinelli F, Biscornet L, DiancourtL, Michel S, Duquerroy S, Guigon G, Frenkiel MP, Brehin AC, CubitoN, Despres P, Kunst F, Rey FA, Zeller H, Brisse S. Genomemicroevolution of chikungunya viruses causing the Indian Oceanoutbreak.PLoS Med. 2006;3:e263.

41. Schwarz TF, Jager G, Gilch S, Pauli C, Eisenhut M, Nitschko H,Hegenscheid B. Travel-related vector-borne virus infections in Ger-many. Arch Virol Suppl. 1996;11:5765.

42. Simon F, Tolou H, Jeandel P. [The unexpected chikungunya outbreak].Rev Med Interne. 2006;27:441.

43. Suhrbier A, La Linn M. Clinical and pathologic aspects of arthritis due

to Ross River virus and other alphaviruses. Curr Opin Rheumatol.2004;16:374379.

44. Thonnon J, Spiegel A, Diallo M, Diallo A, Fontenille D. [Chikungunyavirus outbreak in Senegal in 1996 and 1997]. Bull Soc Pathol Exot.1999;92:7982.

45. Toma L, Severini F, Di Luca M, Bella A, Romi R. Seasonal patterns ofoviposition and egg hatching rate of Aedes albopictus in Rome. J Am

Mosq Control Assoc. 2003;19:1922.46. Weaver SC, Barrett D. Transmission cycles, host range, evolution and

emergence of arboviral disease. Nat Rev Microbiol. 2004;2:789801.47. Woodruff AW, Bowen ET, Platt GS. Viral infections in travellers from

tropical Africa. Br Med J. 1978;1:956958.48. World Tourism Organization. Year Book of Tourism Statistics 2006

(Data 2000-2004). 58th ed. New York: World Tourism Organization;2006.

49. Yergolkar PN, Tandale BV, Arankalle VA, Sathe PS, Sudeep AB,Gandhe SS, Gokhle MD, Jacob GP, Hundekar SL, Mishra AC.

Chikungunya outbreaks caused by African genotype, India. EmergInfect Dis. 2006;12:15801583.



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