MAJOR ARTICLE

Persistent Arthralgia Associated with Chikungunya

Virus: A Study of 88 Adult Patients on Reunion
Island
Gianandrea Borgherini,1 Patrice Poubeau,1 Annie Jossaume,1 Arnaud Gouix,1 Liliane Cotte,2 Alain Michault,3
Claude Arvin-Berod,1 and Fabrice Paganin1
1

Service de Pneumologie et Maladies Infectieuses, 2Centre dInvestigation Clinique, and 3Laboratoire de Virologie, Groupe Hospitalier Sud
Reunion, Saint Pierre, La Reunion, France

Chikungunya virus, an arthropod-borne virus that belongs to the Alphavirus genus of the family Togaviridae,
was first isolated in 1953 [1], during an epidemic of
febrile polyarthralgia occurring in the Makonde plateau
(Tanzania). Since then, chikungunya virus has been the
causative agent of several infection outbreaks in Africa
and Asia [28], where the first documented cases occurred in Thailand in 1958 [9]. The virus is transmitted
to humans by mosquitoes of the genus Aedes (mainly
Aedes aegypti and Aedes albopictus). The 2 main clinical

Received 24 January 2008; accepted 1 April 2008; electronically published 7

July 2008.
Reprints or correspondence: Dr. Gianandrea Borgherini, Service de Pneumologie
et Maladies Infectieuses, Groupe Hospitalier Sud Reunion, BP 350, 97448 Saint
Pierre, La Reunion, France (gianu.borg@wanadoo.fr).
Clinical Infectious Diseases 2008; 47:46975
 2008 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2008/4704-0005$15.00
DOI: 10.1086/590003

features of acute chikungunya virus infection are fever

of sudden onset and severe, often debilitating polyarthralgia. Rash and gastrointestinal symptoms are also
frequent findings [10].
Since June 2004, when the first documented outbreak
occurred in Lamu, Kenya, an epidemic of chikungunya
virus infection has progressively spread to different
countries in the Indian Ocean region [11]. On Reunion
Island, where chikungunya virus infection had never
been previously reported, the first cases were reported
in March 2005, and their number significantly increased
in December 2005 and after [12]. From March 2005
through April 2006, the surveillance system estimated
that 244,000 cases of chikungunya virus infection occurred in a general population of 766,000, with an overall attack rate of 35% [12]. During the Reunion Island
epidemic, unusually severe forms of the disease were
recorded [12], and several cases of maternal-neonatal
transmission were observed for the first time [13].
Arthralgia and Chikungunya Virus Infection CID 2008:47 (15 August) 469

Downloaded from http://cid.oxfordjournals.org/ by guest on December 10, 2015

Background. An outbreak of chikungunya virus infection occurred on Reunion Island during the period 2005
2006. Persistent arthralgia after chikungunya virus infection has been reported, but few studies have treated this
aspect of the disease.
Methods. Adult patients with laboratory-confirmed acute chikungunya virus infection who were referred to
Groupe Hospitalier Sud Reunion during the period 20052006 were asked to participate in the study. Patients
were assessed a mean of 18 months after acute disease occurred. Assessment consisted of answering questions on
a standard form, undergoing a medical examination, and being tested for the presence of IgM antibodies to
chikungunya virus.
Results. Eighty-eight patients (mean age, 58.3 years; male-to-female ratio, 1.1:1.0) were included in this study.
Fifty-eight patients (65.9%) had been hospitalized for acute chikungunya virus infection, and a history of arthralgia
before chikungunya virus infection was reported by 39 patients (44%). Fifty-six patients (63.6%) reported persistent
arthralgia related to chikungunya virus infection, and in almost one-half of the patients, the joint pain had a
negative impact on everyday activities. Arthralgia was polyarticular in all cases, and pain was continuous in 31
patients (55.4%). Overall, 35 patients (39.7%) had test results positive for IgM antibodies to chikungunya virus.
Conclusions. Persistent and disabling arthralgia was a frequent concern in this cohort of patients who had
experienced severe chikungunya virus infection 18 months earlier. Further studies are needed to evaluate the
prevalence of persistent arthralgia in the general population to determine the real burden of the disease.

Table 1. Joint pain in 56 patients with persistent arthralgia.

Patients
(n p 56)

Characteristic
Continuous pain
Intermittent pain

31 (55.4)

Overall

25 (45.6)

At least once per week

At least once per month

12/25 (48)
10/25 (40)

Not specified
Experienced relapse
Mean no. of relapses per patient  SD
Period between acute chikungunya and first relapse, mean months  SD

3/25 (12)
12 (21.4)
1.5  1.2
8  5.4

Morning stiffness
Discomfort in everyday activities

40 (71.4)
26 (46.4)

Symmetrical joint pain

36 (64.3)

NOTE. Data are no. (%) or proportion (%) of patients, unless otherwise indicated.

PATIENTS AND METHODS

Reunion Island is a French overseas territory located in the
southwestern part of the Indian Ocean, east of Madagascar.
The medical system and accessibility to medical care are the
470 CID 2008:47 (15 August) Borgherini et al.

same as in France. The Groupe Hospitalier Sud Reunion is a

tertiary nonteaching institution with a referral population of
350,000 individuals.
Patients. We studied a cohort of patients with laboratoryconfirmed acute chikungunya virus infection who were referred
to our institution from March 2005 through April 2006. For
this cohort, the following inclusion criteria had to be met: age
16 years, clinical presentation consistent with chikungunya
virus infection (e.g., abrupt onset of fever and/or polyarthralgia), onset of symptoms within 10 days preceding the referral,
and laboratory confirmation of chikungunya virus infection by
positive RT-PCR results, paired serum sample seroconversion,
or positive IgM serologic test results. For all of the patients,
data on clinical features and laboratory findings during the
acute phase of illness were available. All of the enrolled patients
were contacted by telephone (when the telephone number was
available in the medical file), several times if necessary, by a
member of the Centre dInvestigation Clinique and invited to
participate to the study. All the patients consented to their
involvement in the study.
Assessments. Patients were assessed in our department
(Service de Pneumologie et Maladies Infectieuses, Groupe Hospitalier Sud Reunion; Saint Pierre, La Reunion, France) from
August 2007 through October 2007 and were assessed a mean
(SD) of 18.7  2.1 months after acute illness. Three physicians interrogated the patients using a standard form and performed the physical examination. The standard form was used
for abstracting previous history of arthralgia and the nature of
current symptoms (i.e., their frequency, localization, and impact on everyday life).
We defined persistent arthralgia as an intermittent or continuous joint pain that, in the judgment of the patient, was
related to chikungunya virus infection. If the patient was already
affected by joint pain before acute chikungunya virus infection,

Downloaded from http://cid.oxfordjournals.org/ by guest on December 10, 2015

Throughout the Indian Ocean epidemic, imported cases of

chikungunya virus infection in travelers returning from affected
areas were reported in several European and American countries [1417]. In August 2007, autochthonous cases of chikungunya virus infection were detected in northeastern Italy [18],
the first time that this disease occurred in a temperate country.
The presence of 1 of the competent vectors, A. albopictus, in
a growing number of countries and the always-increasing number of international travelers raise major concerns about the
introduction of chikungunya virus into other previously unexposed areas.
Although the clinical features of acute chikungunya virus
infection have already been described in several reports [1, 10,
19], little is known about the long-term outcomes of the disease.
Persistent arthralgia was already observed by Robinson [1] in
the first description of chikungunya virus infection, but the
only study that evaluated long-term persistent arthralgia in a
substantial number of patients was by Brighton et al. [20] in
1983; this study examined a group of South African patients 3
years after the acute phase of illness. In the report by Brighton
et al. [20], in which almost one-half of the patients were !17
years of age, most patients were fully recovered within 1 year.
In our experience, the persistence of arthralgia in adult patients
from Reunion Island appeared to be more significant than in
report by Brighton et al. [20] which incited us to perform our
study. Our studys objectives were to evaluate the prevalence
and nature of and risk factors associated with persistent arthralgia in a population previously affected by acute chikungunya virus infection.

Table 2. Localization of joint pain in 56 patients with persistent

arthralgia.

Characteristic
Mean no. of involved joints  SD
Localization

Self-reported Pain on physical

pain
examination
6.2  4.2

3  3.8

Metacarpophalangeal joints

32 (57.1)

15 (26.8)

Metatarsal joints
Wrists

27 (48.2)
28 (50)

15 (26.8)
9 (16.1)

Ankles
Elbows

26 (46.4)
13 (23.2)

16 (28.6)
8 (14.3)

Shoulders
Knees

25 (44.6)
32 (57.1)

17 (30.4)
12 (21.4)

Rachis
Sternoclavicular joints

13 (23.2)
1 (1.8)

7 (12.5)
1 (1.8)

Hips

10 (17.9)

3 (5.4)

arthralgia was considered to be secondary to chikungunya virus

infection if it differed in intensity or localization from the prior
symptoms. Arthralgia was considered to be continuous when
joint pain was present every day, even if it fluctuated in severity.
For the patients who presented with intermittent arthralgia, we
determined the localization of the joint pain during the most
recent episode of arthralgia. Relapse was defined as a bout of
joint pain that lasted 11 day with an intensity that was equivalent to or greater than that associated with acute illness and
that occurred 11 month after acute chikungunya virus infection
after a symptom-free period of 11 month.
The physical examination was focused on articular signs;
all of the joints were inspected for the presence of swelling
and checked for pain elicited by passive movement. All the
patients were tested for the presence of IgM antibodies to
chikungunya virus in serum samples obtained on the day of
the assessment. Chikungunya virusspecific IgM antibody was
detected by IgM-capture ELISA using a chikungunya virus
antigen produced by the Centre National de Re`ference des
Arbovirus (Lyon, France) [21].
Statistical analysis. Results are expressed as mean value
(SD) and as number (percentage) of patients. The MannWhitney U test was used to calculate differences in laboratory
findings and continuous variables between patients with persistent arthralgia and patients who had experienced recovery.
Analysis was conducted using the x2 test, with use of Fishers
exact test, as needed, for comparison of categorical variables
between patients with persistent arthralgia and patients who
had experienced recovery. P ! .05 was considered to be statistically significant.
RESULTS
A total of 202 patients who fulfilled the inclusion criteria were
identified. The mean age (SD) of the patients was 57.7 

Arthralgia and Chikungunya Virus Infection CID 2008:47 (15 August) 471

Downloaded from http://cid.oxfordjournals.org/ by guest on December 10, 2015

NOTE. Data are no. (%) of patients, unless otherwise indicated.

19.9 years; the male-to-female ratio was 1.1:1.0. For 60 patients

(29.7%), the telephone number was unavailable or incorrect.
One hundred forty-two households were contacted by telephone. Sixteen (7.9%) of 202 patients died in the months after
acute illness. The mean age (SD) of the patients who died
was 74.6  11.2 years; the male-to-female ratio of the patients
who died was 1.3:1.0. In 8 patients, it was possible to assess
the cause of death; in each case, death was secondary to an
aggravation of an underlying disease. Of the 126 patients who
were contacted by telephone, 36 (28.6%) did not agree to participate or were unable to participate in the study. Two patients
were secondarily excluded, because they were not tested for
IgM antibodies.
Eighty-eight patients were included in this study. The mean
age (SD) age was 58.3  18 years; the male-female ratio was
1.1:1.0. At least 1 underlying illness was present in 63 patients
(71.6%); the most frequent illnesses were hypertension and
diabetes mellitus. A history of chronic arthralgia preceding the
chikungunya virus infection was reported by 39 patients
(44.3%). The 2 most frequently reported causes of arthralgia
were osteoarthritis (26 patients; 66.6%) and gout (7 patients;
17.9%).
Fifty-eight patients (65.9%) had been hospitalized with acute
chikungunya virus infection. Among the patients included in
the study, the laboratory diagnosis of acute chikungunya virus
infection was made by positive RT-PCR results in 31 patients,
seroconversion in 7 patients, and positive IgM test results in
50 patients. The mean delay (SD) between onset of symptoms
and IgM positivity was 10.1  6.5 days. At the time of assessment, test results were still positive for IgM antibodies specific
to chikungunya virus in 35 patients (39.7%).
At the time of assessment, 32 patients (36.4%) considered
themselves to have recovered from arthralgia related to chikungunya virus infection. For these patients, the mean duration
of chikungunya virusrelated arthralgia (SD) was 2.9  2.4
months. In this group, 10 patients, all of whom had already
been affected by chronic arthralgia before chikungunya virus
infection, were still experiencing joint pain at the time of assessment that they attributed to the preexisting illness. Relapse
of joint pain was reported by 1 patient.
At the time of assessment, 56 patients (63.8%) reported persistent arthralgia related to chikungunya virus infection. The
nature and localizations of arthralgia are summarized in tables
1 and 2. For 31 patients (55.4%), joint pain was continuous.
Arthralgia was polyarticular in all patients. Discomfort in performing the activities of everyday life (e.g., walking, eating, and
getting dressed) was identified in 26 patients (46.4%). Relapses
were reported by 12 patients (21%). Joint swelling, which was
mainly observed in the ankles, was noted in 9 patients (16.1%).
Taking self-reported pain into consideration, metacarpophalangeal joints (in 57.1% of patients) and knees (57.1%) were

35
aminotransferase level, mean U/L  SD (reference range, 865 U/L)
01
35

12/32 (37.5)
18.7  1.9
23/32 (71.8)
11/30 (36.7)
5/32 (15.6)
9/32
10/32
21/32
15/30

29/56 (51.8)
18.7  2.1
40/56 (71.4)
23/52 (44.2)
21/56 (37.5)
18/56
29/56
37/56
21/54

67.7  49.2
70.6  36
46.4  39.3
65.5  48
379  716
14/32 (43.7)
23.7  24.2

44.5  32.5
35.8  12.5
35.8  35.5
28.5  18
191  173
21/56 (37.5)
30  37

Gastrointestinal symptoms included diarrhea, vomiting, and/or abdominal pain.

Threshold for a positive serologic test result, 20.

686
54.5
61
0.15











926
55
113
2.22

146  68
117  49

174  61
193  95
511
34.9
74
0.16

16/30 (53.3)
1/32 (3.1)

31/55 (56.4)
12/56 (21)

856
38.3
105
2.26

18/28 (64.3)

28/56 (50)

(28)
(31.2)
(65.6)
(50)

20/32 (62.5)

27/56 (48.2)

(32)
(51.8)
(66)
(38.8)

56.2  21

59.8  17

NOTE. Data are no. or proportion of patients (%), unless otherwise indicated. Days are days from the onset of symptoms during acute chikungunya virus infection.

Creatinine kinase level on days 01, mean U/L  SD (reference range, 20210 U/L)
Positive IgM serologic test result
Mean IgM antibodies titer  SDb

Days
Alanine
Days
Days

Days 01

Aspartate aminotransferase level, mean U/L  SD (reference range, 845 U/L)

Lymphocyte count on days 01, mean cells/mm3  SD (reference range, 10004000 cells/mm3)
C-reactive protein level on days 01, mean mg/dL  SD (reference range, 112 mg/dL)
Creatinine level on days 01, mean mmol/L  SD (reference range, 50120 mmol/L)
Serum calcium level on days 01, mean mmol/L  SD (reference range, 2.252.65 mmol/L)

Rash during acute chikungunya virus infection

Gastrointestinal symptoms during acute chikungunya virus infectiona
Relapse
Platelet count, mean platelets 103 platelets/mm3  SD (reference range, 150500 103 platelets/mm3)
Days 01
Days 35

Diabetes mellitus
Preexisting arthralgia
Hospitalization during acute chikungunya virus infection
Swollen joints during acute chikungunya virus

Period between acute chikungunya virus infection and assessment, mean months  SD
Comorbidity
Blood hypertension
Ischemic heart disease

Female

Age, mean years  SD

Sex
Male

Characteristic

Patients with
Patients who
persistent arthralgia experienced recovery
(n p 56)
(n p 32)

Table 3. Demographic data and clinical and laboratory findings for patients with persistent arthralgia and patients who experienced recovery.

Downloaded from http://cid.oxfordjournals.org/ by guest on December 10, 2015

.90
.65
.75

.05
.001

.001

.01

.76
.18
.15
.37

.03
.006

.82
.03

.82

.81
.07
1.99
.64

.64
.06

1.99

.70

.62
.26

the most affected joints; on physical examination, shoulders

(30.4%) and ankles (28.6%) were more frequently involved.
Patients with persistent arthralgia and patients who had experienced recovery were compared. Analysis of demographic
data and clinical and laboratory findings during acute chikungunya virus infection was performed, and the results are reported in table 3.
In the group of patients who experienced recovery, thrombocytopenia and elevated liver enzyme levels were significantly
more common on days 01 and days 35. Comparison of other
laboratory findings on days 35 are not reported in table 3,
because they did not reveal any statistically significant difference.
DISCUSSION

Arthralgia and Chikungunya Virus Infection CID 2008:47 (15 August) 473

Downloaded from http://cid.oxfordjournals.org/ by guest on December 10, 2015

The recent Indian Ocean epidemic and the Italian outbreak in

2007 [18] have drawn new attention to chikungunya virus infection, a long-neglected disease. Still, many aspects of this
disease have been poorly studied. Although it is already well
established that severe arthralgia is one of the hallmark clinical
features of acute chikungunya virus infection [1, 10, 19, 22,
23], little is known about the long-term persistence of this
symptom.
In our study, 56 (63.8%) of the enrolled patients were still
presenting with joint pain 18 months after acute chikungunya
virus infection that, in their judgment, was secondary to the
chikungunya virus infection. Persistent arthralgia (always polyarticular) was continuous for 31 (55.4%) of these patients,
and almost one-half of them reported some difficulties in performing activities of daily life.
To our knowledge, only 1 other report in the international
literature has studied long-term, persistent arthralgia in a large
group of patients with laboratory-confirmed chikungunya virus
infection [20]. In this study, performed in South Africa in 1980
by Brighton et al. [20], in which several patients were questioned only by telephone, 94 (87.9%) of 107 patients were free
of symptoms 35 years after acute infection. The discordance
between this study [20], which reported a much higher proportion of patients who experienced recovery, and our study
can be easily explained. In the study by Brighton et al. [20],
patients were assessed later than they were in our study, and
almost one-half of the patients were !17 years of age; it is
known that arthralgia has a milder course in children [24, 25].
In a more recent French report with a shorter-term follow-up,
Simon et al. [23] studied a cohort of 47 travelers (46 adults
and 1 infant; mean age, 45.1 years) returning from the Indian
Ocean islands. In this series, in which 11 patients required
hospitalization, 48% of patients were still symptomatic 6
months after disease onset.
The other objective of our study was to identify the possible
predictors of persistent arthralgia; therefore, we compared several risk factors in the group of patients who experienced re-

covery and the group of patients who still had arthralgia. A

lower platelet count and an elevation of liver enzyme levels
during acute chikungunya virus infection in patients who experienced recovery and a higher number of relapses among the
patients with persistent arthralgia were the only significant differences between the 2 groups. The laboratory results could
suggest that a more severe acute illness can predict, paradoxically, a favorable outcome, but the clinical significance of this
finding is uncertain.
Relapse of severe joint pain was reported by 12 (21.4%) of
the patients, confirming the fluctuating nature of arthralgia
associated with chikungunya virus infection. Relapses of arthralgia have already been reported by other authors [23, 26]
as being a common feature in the months after acute chikungunya virus infection; however, in these previous studies, no
definition of relapse was given. We have tried to eliminate this
bias in our study to obtain a more accurate estimation of the
finding.
Preexisting joint pain, which has been significantly associated
with a worse evolution of Ross River virus infection [27], was
more frequent among patients with persistent arthralgia, although the difference was not statistically significant.
A previous seroprevalence study [21] found that 55.5% of
patients were IgM positive 1318 months after acute chikungunya virus infection; this study shows an unusual persistence
of specific IgM antibodies, with 25 (39.7%) of 45 patients testing IgM positive. It is noteworthy that, for infection due to
West Nile virus [28], which is another arborvirus associated
with long-term sequelae, the same phenomenon has been observed. The pathogenesis of arthropathy in chikungunya virus
infection has not yet been clearly understood, but it is likely
that, as with Ross River virus infection [29], the immune response plays an essential role. Therefore, it was particularly
interesting to check whether there was any statistically significant association between the presence of IgM antibodies and
persistent arthralgia. This association has been ruled out in our
study, in which the prevalence of positive IgM test results was
even higher among the patients who experienced recovery.
Our report has several limitations. We relied on the voluntary
participation of individuals from a retrospective cohort, and
one-quarter of the patients who were contacted did not participate in the study. Therefore, the possibility of selection bias,
particularly in favor of patients with more-severe illness, has
to be considered. The enrolled individuals represent a group
of patients who presented with a more-severe form of chikungunya virus infection, who often need hospitalization and cannot be considered to be representative of the general population. In addition, our cohort was largely composed of
middle-aged and elderly people, which partially reflects the
estimate of the surveillance system on Reunion Island, which
found a predominance of adults in the affected population [12].

474 CID 2008:47 (15 August) Borgherini et al.

productivity is a frequent concern; a study conducted among

hospital staff on Reunion Island found that 76.8% of affected
patients took time off from work [26]. In another report [34],
in a population of military policemen, quality of life was still
severely impaired several weeks after acute infection. Even
though it has limitations, our study shows how persistent arthralgia, often continuous and debilitating, is a frequent concern among patients with chikungunya virus infection. This is
especially the case among middle-aged and elderly patients, one
of the populations most affected in the recent epidemics. Further consultations and hospitalizations may be needed because
of the pain and disability associated with chikungunya virus
infection; this should be included in the assessment of the
overall economic impact of chikungunya virus infection, a disease which, considering the globalization of one of its competent vectors, A. albopictus, is at risk of becoming a major
public health threat. To have a more accurate estimate of persistent arthralgia related to chikungunya virus infection in the
general population, a prospective, case-control study that involves a larger number of patients and includes patients with
milder forms of the disease at the acute stage is needed.
Acknowledgments
We thank Ms. Corinne Mussard, for tracing the patients and contacting
them by telephone, and the senior nurse, nurses, and secretaries of our
department, for their help.
Potential conflict of interests. All authors: no conflicts.

References
1. Robinson MC. An epidemic of virus disease in Southern Province,
Tanganyika Territory, in 195253. I. Clinical features. Trans R Soc Trop
Med Hyg 1955; 49:2832.
2. Thaung U, Ming CK, Swe T, Thein S. Epidemiological features of
dengue and chikungunya infections in Burma. Southeast Asian J Trop
Med Public Health 1975; 6:27683.
3. Saluzzo JF, Cornet M, Digoutte JP. Outbreak of a Chikungunya virus
epidemic in western Senegal in 1982 [in French]. Dakar Med 1983;
28:497500.
4. Thonnon J, Spiegel A, Diallo M, Diallo A, Fontenille D. Chikungunya
virus outbreak in Senegal in 1996 and 1997 [in French]. Bull Soc Pathol
Exot 1999; 92:7982.
5. Thaikruea L, Charearnsook O, Reanphumkarnkit S, et al. Chikungunya
in Thailand: a re-emerging disease? Southeast Asian J Trop Med Public
Health 1997; 28:35964.
6. Muyembe-Tamfum JJ, Peyrefitte CN, Yogolelo R, et al. Epidemic of
Chikungunya virus in 1999 and 2000 in the Democratic Republic of
the Congo [in French]. Med Trop 2003; 63:6378.
7. Lam SK, Chua KB, Hooi PS, et al. Chikungunya infection: an emerging
disease in Malaysia. Southeast Asian J Trop Med Public Health 2001;32:
44751.
8. Laras K, Sukri NC, Larasati RP, et al. Tracking the reemergence of
epidemic chikungunya virus in Indonesia. Trans R Soc Trop Med Hyg
2005; 99:12841.
9. Hammon WM, Rudnick A, Sather GE. Viruses associated with epidemic hemorrhagic fevers of the Philippines and Thailand. Science
1960; 131:11023.
10. Borgherini G, Poubeau P, Staikowsky F, et al. Outbreak of Chikungunya
on Reunion Island: early clinical and laboratory features in 157 adult
patients. Clin Infect Dis 2007; 44:14017.

Downloaded from http://cid.oxfordjournals.org/ by guest on December 10, 2015

The same age distribution was reported in the recent Italian

outbreak, in which the median age of the patients affected by
chikungunya virus infection was 61 years [18]. Another bias
of this study is related to the subjectivity of the symptoms.
Although we tried to reduce this bias by directly questioning
the patients and performing physical examinations, it was
clearly difficult to objectively assess the relationship between
persistent arthralgia and chikungunya virus infection. Apart
from elicited pain, findings on physical examination were
scarce, and in the few patients who presented with swollen
joints (usually the ankles), this sign could be attributed to other
underlying illnesses. The discordance between the localization
of self-reported pain and the findings on physical examination
can be seen as a consequence of the doubtful reliability of selfreported symptoms; however, we have to remember that many
patients reported intermittent pain and, therefore, were symptom free the day of the assessment; in addition, another characteristic of chikungunya virusrelated arthralgia is its migratory nature.
A further issue was the fact that 29 of 56 patients with persistent arthralgia reported a prior history of joint symptoms,
which made establishing the real cause of joint pain difficult.
For this reason, we used a definition of persistent arthralgia
that was designed to reduce this bias, stressing how the present
pain was not comparable to previous pain.
The fact that, among the patients who experienced recovery,
10 patients still had arthralgia but did not attribute their joint
pain to chikungunya virus infection (because the pain was similar to that which they felt before the infection) seems to indicate that patients can differentiate the nature of their pain.
Even if we had not considered patients with previous arthralgia,
the proportion of patients still affected by persistent arthralgia
(30.7%) would have been noteworthy. This difficulty in relating
a persistent joint pain to a viral arthritis has already been reported [27, 3032] for Ross River virus infection, for which
several surveys regarding the evolution of rheumatic manifestations have produced conflicting data.
We could have obtained more-reliable data by comparing
our group of patients with a control group of uninfected patients. However, several issues made this kind of study difficult
to perform on Reunion Island. As previously shown by a seroprevalence study [33], 38% of the general population on
Reunion Island were infected by chikungunya virus during the
20052006 outbreak. The proportion of infected patients was
even higher in the southern part of the island, where our institution is located, and a seroprevalence 150% was reported
among the elderly patients, which made recruitment of an uninfected control group problematic.
The real burden of chikungunya virus infectiona disease
that, for a long time, was considered to be benignhas yet to
be precisely estimated. At the acute stage of the illness, lost

24. Moore DL, Reddy S, Akinkugbe FM, et al. An epidemic of chikungunya

fever at Ibadan, Nigeria, 1969. Ann Trop Med Parasitol 1974; 68:5968.
25. Halstead SB, Nimmannitya S, Margiotta MR. Dengue and chikungunya
virus infection in man in Thailand, 19621964. II. Observations on
disease in outpatients. Am J Trop Med Hyg 1969; 18:97283.
26. Staikowsky F, Le Roux K, Schuffenecker I, et al. Retrospective survey
of Chikungunya disease in Reunion Island hospital staff. Epidemiol
Infect 2008; 136:196206.
27. Mylonas AD, Brown AM, Carthew TL, et al. Natural history of Ross
River virusinduced epidemic polyarthritis. Med J Aust 2002; 177:
35660.
28. Carson PJ, Konewko P, Wold KS, et al. Long-term clinical and neuropsychological outcomes of West Nile virus infection. Clin Infect Dis
2006; 43:72330.
29. Rulli NE, Melton J, Wilmes A, Ewart G, Mahalingam S. The molecular
and cellular aspects of arthritis due to alphavirus infections: lesson
learned from Ross River virus. Ann N Y Acad Sci 2007; 1102:96108.
30. Harley D, Bossingham D, Purdie DM, et al. Ross River virus disease
in tropical Queensland: evolution of rheumatic manifestations in an
inception cohort followed for six months. Med J Aust 2002; 177:3525.
31. Fraser JR. Epidemic polyarthritis and Ross River virus disease. Clin
Rheum Dis 1986; 12:36988.
32. Selden SM, Cameron AS. Changing epidemiology of Ross River virus
disease in South Australia. Med J Aust 1996; 165:3137.
33. Perrau J, Fianu A, Le Roux K, et al. Enquete de seroprevalence du
Chikungunya en population generale. La Reunion. Hiver austral 2006.
In : Program and abstracts of Colloque international: Chikungunya et
autres arboviroses emergentes en milieu tropical (Saint Pierre). La
Reunion, France. Bull Soc Pathol Exot 2007; 100:329. Available at: http:
//www.invs.sante.fr/publications/2008/colloque_chik_dec_2007/26_
perrau.pdf. Accessed 1 July 2008.
34. Queyriaux B, Simon F, Grandadam M, Michel R, Tolou H, Boutin JP.
Clinical burden of chikungunya virus infection. Lancet Infect Dis
2008; 8:23.

Arthralgia and Chikungunya Virus Infection CID 2008:47 (15 August) 475

Downloaded from http://cid.oxfordjournals.org/ by guest on December 10, 2015

11. Sergon K, Njuguna C, Kalani R, et al. Seroprevalence of Chikungunya

virus (CHIKV) infection on Lamu Island, Kenya, October 2004. Am
J Trop Med Hyg 2008; 78:3337.
12. Renault P, Solet JL, Sissoko D, et al. A major epidemic of chikungunya
virus infection on Reunion Island, France, 20052006. Am J Trop Med
Hyg 2007; 77:72731.
13. Ramful D, Carbonnier M, Pasquet M, et al. Mother-to-child transmission of Chikungunya virus infection. Pediatr Infect Dis J 2007; 26:
8115.
14. Hochedez P, Jaureguiberry S, Debruyne M, et al. Chikungunya infection in travelers. Emerg Infect Dis 2006; 12:15657.
15. Taubitz W, Cramer JP, Kapaun A, et al. Chikungunya fever in travelers:
clinical presentation and course. Clin Infect Dis 2007; 45:e14.
16. Lanciotti RS, Kosoy OL, Laven JJ, et al. Chikungunya virus in US
travelers returning from India, 2006. Emerg Infect Dis 2007; 13:7647.
17. Beltrame A, Angheben A, Bisoffi Z, et al. Imported Chikungunya infection, Italy. Emerg Infect Dis 2007; 13:12646.
18. Rezza G, Nicoletti L, Angelini R, et al. Infection with chikungunya
virus in Italy: an outbreak in a temperate region. Lancet 2007; 370:
18406.
19. Thiruvengadam KV, Kalyanasundaram V, Rajgopal J. Clinical and pathological studies on chikungunya fever in Madras city. Indian J Med
Res 1965; 53:72944.
20. Brighton SW, Prozesky OW, De La Harpe AL. Chikungunya virus
infection: a retrospective study of 107 cases. S Afr Med J 1983; 63:
3135.
21. Grivard P, Le Roux K, Laurent P, et al. Molecular and serological
diagnosis of Chikungunya virus infection. Pathol Biol 2007; 55:4904.
22. Kennedy AC, Fleming J, Solomon L. Chikungunya viral arthropathy:
a clinical description. J Rheumatol 1980; 7:2316.
23. Simon F, Parola P, Grandadam M, et al. Chikungunya infection: an
emerging rheumatism among travelers returned from Indian Ocean
islands: report of 47 cases. Medicine 2007; 86:12337.