Conceived and designed the experiments: MKS PYB JP AF TH. Performed the experiments: MKS. Analyzed the data: MKS PYB JP DM TH. Contributed reagents/materials/analysis tools: MKS PG JP AF FF. Wrote the paper: MKS PG PYB JP AF JP DM AF FF TH. Managed and analysed the SEROCHIK survey database: JP AF. Main investigator of the SEROCHIK survey: FF.
The authors have declared that no competing interests exist.
Persistent symptoms, mainly joint and muscular pain and depression, have been reported several months after Chikungunya virus (CHIKV) infection. Their frequency and their impact on quality of life have not been compared with those of an unexposed population. In the present study, we aimed to describe the frequency of prolonged clinical manifestations of CHIKV infection and to measure the impact on quality of life and health care consumption in comparison with that of an unexposed population, more than one year after infection.
In a retrospective cohort study, 199 subjects who had serologically confirmed CHIKV infection (CHIK+) were compared with 199 sero-negative subjects (CHIK–) matched for age, gender and area of residence in La Réunion Island. Following an average time of 17 months from the acute phase of infection, participants were interviewed by telephone about current symptoms, medical consumption during the last 12 months and quality of life assessed by the 12-items Short-Form Health Survey (SF-12) scale. At the time of study, 112 (56%) CHIK+ persons reported they were fully recovered. CHIK+ complained more frequently than CHIK– of arthralgia (relative risk = 1.9; 95% confidence interval: 1.6–2.2), myalgia (1.9; 1.5–2.3), fatigue (2.3; 1.8–3), depression (2.5; 1.5–4.1) and hair loss (3.8; 1.9–7.6). There was no significant difference between CHIK+ and CHIK– subjects regarding medical consumption in the past year. The mean (SD) score of the SF-12 Physical Component Summary was 46.4 (10.8) in CHIK+ versus 49.1 (9.3) in CHIK– (p = 0.04). There was no significant difference between the two groups for the Mental Component Summary.
More than one year following the acute phase of infection, CHIK+ subjects reported more disabilities than those who were CHIK–. These persistent disabilities, however, have no significant influence on medical consumption, and the impact on quality of life is moderate.
Chikungunya is a disease caused by an arboviral alphavirus transmitted to humans by
Chikungunya virus (CHIKV) is an enveloped, RNA positive-strand Alphavirus belonging to the Togaviridae family
Nevertheless, several authors have reported persistent clinical manifestations (mainly joint and muscular pain and depression) several months after acute infection, leading some of them to consider the possibility of chronic forms of Chikungunya infection
We conducted an investigation to describe the frequency of late clinical manifestations of Chikungunya virus infection and to measure the impact on quality of life and health care consumption, compared with an uninfected population, in the context of the epidemic occurring in La Réunion Island.
Among the 434 people contacted, 27 refused to respond to the questionnaire and 9 were excluded from the analysis because of the impossibility of matching, leaving 199 pairs for analysis. The participation rate was 92% (398 out of 434).
The mean age of the study population was 42 years (range: 2–91).
Sociodemographic characteristics | Number of people/total number of participants (%) |
Female | 202/398 (51) |
Male | 196/398 (49) |
Under 30 | 136/398 (34) |
30 to 59 | 158/398 (40) |
60 and over | 104/398 (26) |
North | 94/398 (24) |
South | 104/398 (26) |
East | 100/398 (25) |
West | 100/398 (25) |
Following an average time of 17 months (range: 5–28) from the acute phase of disease, 112 of the 199 CHIK+ subjects (56%) reported that they were fully recovered. The CHIK+ subjects aged under 30 reported a faster recovery than the older subjects (75% versus 40% at one year; p<0.001) (
The long dash followed by the short dash represents patients aged under 30; the dash represents patients aged 30 to 59 and the solid line represents those aged 60 and over. Recovery is fast in young subjects.
Symptoms at the time of study are shown in
CHIK+ | CHIK– | |||
Symptoms | n (%) | n (%) | RR |
p-Value |
105 (53) | 56 (28) | 1.9 [1.6–2.2] | <0.001 | |
Upper limbs | 76 (38) | 29 (15) | 2.6 [2.0–3.3] | <0.001 |
Lower limbs | 83 (42) | 33 (17) | 2.5 [2.0–3.2] | <0.001 |
Spine | 43 (22) | 25 (13) | 1.7 [1.2–2.3] | 0.01 |
84 (42) | 45 (23) | 1.9 [1.5–2.3] | <0.001 | |
71 (36) | 31 (16) | 2.3 [1.8–3.0] | <0.001 | |
25 (13) | 10 (5) | 2.5 [1.5–4.1] | 0.014 | |
19 (10) | 5 (3) | 3.8 [1.9–7.6] | 0.007 | |
20 (10) | 10 (5) | 2.0 [1.2–3.4] | 0.087 | |
55 (28) | 39 (20) | 1.4 [1.1–1.8] | 0.076 | |
12 (6) | 11 (6) | 1.1 [0.6–1.9] | 1 | |
Taking analgesic | 52 (26) | 45 (23) | 1.2 [1.0–1.4] | 0.42 |
Medical consultations | 159 (80) | 169 (85) | 0.9 [0.9–1.0] | 0.25 |
Hospitalization | 14 (7) | 18 (9) | 0.8 [0.5–1.2] | 0.57 |
CHIK+, persons with a history of CHIKV infection confirmed by serology (n = 199); CHIK–, persons confirmed as seronegative for CHIKV (n = 199); RR, relative risks; CI, confidence interval.
RR, relative risks controlling for stratification criteria.
Exact Mac Nemar test.
There was no significant difference between CHIK+ and CHIK– subjects in the frequency of use of analgesics, medical consultations or hospitalizations in the last 12 months (
Quality of life was assessed in all subjects aged 15 or over (N = 324). The average score (SD) of the physical component summary (PCS) was significantly lower in CHIK+ subjects than CHIK– (46.4 (10.8) versus 49.1 (9.3)) (
CHIK+ | CHIK– | ||
SF-12 component summaries | mean score (SD) | mean score (SD) | p-Value |
46.4 (10.8) | 49.1 (9.3) | 0.04 | |
Under 30 | 53.4 (5.1) | 52.8 (6.0) | 0.66 |
30 to 59 | 46.0 (10.4) | 50.2 (8.2) | 0.02 |
60 and over | 42.5 (11.9) | 45 (11.0) | 0.35 |
Female | 45 (11.2) | 48.9 (9.6) | 0.02 |
Male | 47.9 (10.0) | 49.2 (9.0) | 0.71 |
45.5 (11.1) | 45.6 (10.1) | 0.83 | |
Under 30 | 46.4 (9.7) | 46.1 (9.5) | 0.97 |
30 to 59 | 43.9 (11.7) | 44.7 (9.5) | 0.58 |
60 and over | 47.3 (10.9) | 46.4 (11.4) | 0.84 |
Female | 43.8 (11.2) | 43.9 (10.8) | 0.81 |
Male | 47.5 (10.8) | 47.2 (9.1) | 0.91 |
CHIK+, persons with a history of CHIKV infection confirmed by serology (n = 162); CHIK–, persons confirmed as seronegative for CHIKV (n = 162).
Wilcoxon's rank test for paired samples.
After Bonferroni correction, the statistical significance was then set at p = 0.01 with a bilateral formulation.
Compared with the CHIK– subjects, the CHIK+ subjects' worst score for the PCS was found in patients aged 30 to 59 and in females (
Here we report a comparative study of longstanding disabilities owing to CHIKV infection as they are reported within the community. It showed that several subjective symptoms (arthralgia, myalgia, fatigue, depression, hair loss) reported by people infected by CHIKV more than one year after acute infection may be attributable largely (46.4 to 73.7%) to the past infection. The perceived quality of life in these subjects was barely changed, however, as demonstrated by the SF-12. In addition, CHIKV infection was shown to have no significant impact on the use of analgesics, medical consultations or hospitalizations.
To the best of our knowledge, no controlled survey had yet attempted to establish the accountability of an arbovirosis, both on the persistence of non-specific symptoms and on their impact on quality of life in a community. Existence of a “chronic form” of the disease following CHIKV infection had been suggested by uncontrolled observational studies previously reported
Chronic symptoms following infection with other “arthritogenic” alphaviruses such as Ross River virus and Sindbis-related virus have been reported previously in series of case studies
The basis for the musculoskeletal symptoms of Chikungunya disease is still poorly understood
A post-infective fatigue syndrome similar to the symptoms reported here by CHIK+ patients (i.e. disabling fatigue, musculoskeletal pain, neurocognitive difficulties and mood disturbance) has been shown to persist for six months or more in 12% of persons following a variety of acute infections, including Ross River virus
Little attention was paid to scalp lesions in CHIKV infection. However, in the field of alphaviral infections, hair loss is consistent with alopecia encountered in a mice model of Chikungunya infection
Quality of life was already assessed with the SF-12 in other rheumatic conditions, such as rheumatoid arthritis, osteoarthritis and fibromyalgia
There is no clear explanation why patients under the age of 30 reported faster recovery compared to those older than 30. Older age and severe initial joint pain have been recognized as risk factors for non-recovery
Our report has some strengths and limitations. The investigator was not blinded to the serological status of the subjects; participants were questioned about symptoms long after the acute phase of the disease. Also patients were not examined so alternative diagnoses could not be excluded. However, in contrast with previous studies, a standardized health status questionnaire was used and administered by only one investigator, a validated generic quality of health assessment tool was used (the SF-12), a control group was included for comparison and participants were randomly selected through a population-based cohort
Whilst there is appreciable temporary disability associated with acute CHIKV infection, and even though more frequent manifestations are reported by infected persons more than a year after the acute phase of the condition, the resulting impact on quality of life and medical consumption seems moderate. Despite alarming signs observed throughout the outbreak in La Réunion, such as reports of severe atypical forms
We conducted a retrospective cohort study to compare subjects who had been infected by CHIKV during the 2005 and 2006 outbreaks in La Réunion Island with those who had not been infected. The study sample was derived from the SEROCHIK survey, a cross-sectional, population-based seroprevalence study aimed at assessing the prevalence of CHIKV infection in the community soon after the 2006 outbreak
From this population, we selected pairs of subjects with one subject with serologically confirmed CHIKV infection (CHIK+) and one matched subject with negative serology (CHIK–). Pairs of subjects were obtained by balanced random sampling without replacement from 24 strata defined by a unique combination of age (<30 years old, 30 to 59 years and ≥60 years), gender and area of residence (north, south, east and west of the island area).
La Réunion is a French overseas department of 787,836 inhabitants located on a volcanic island of 2511 km2 belonging to the Mascarene Islands in the south-western Indian Ocean. Between 2005 and 2006, a Chikungunya outbreak occurred in La Réunion, in which 38.2% of inhabitants became infected
Participants were interviewed by telephone between March and June 2007. The questionnaire was administered by one investigator (MKS), using closed questions addressing current symptoms, medical consumption during the last 12 months (consultation, hospitalization and use of analgesics) and quality of life assessed by the SF-12 scale
The patients were questioned about the presence or absence of symptoms on the day of the telephone interview. Illness history was recorded during the interview using questions formulated in lay terms. They were asked if they were currently experiencing the following: joint pain (for arthralgia), muscle aches (for myalgia), fatigue, depression, hair loss, skin disorders, sleep disorders or digestive disorders such as nausea, vomiting or diarrhea. When patients reported presence of arthralgia, they were asked to localize the involved joints.
The SF-12 explores the physical and mental aspects of quality of life
For children under eight, the questionnaire was completed by parents. The SF-12 scale addresses only people of 16 years and over.
We considered that an absolute difference of 15% in the frequency of musculoskeletal (e.g. arthralgia or myalgia) symptoms between CHIK+ and CHIK– subjects would be of interest. It has been reported that about 45% of the adult population suffer musculoskeletal pain
Assessment of explanatory variables was conducted by univariate analysis. For paired samples, qualitative variables were analysed using exact Mac Nemar's test and continuous variables (SF-12 components) were analysed using Wilcoxon's rank test. Adjusted relative risks (RR) and their 95% confidence interval (95% CI) were calculated for each persisting symptom controlling for stratification criteria (age, gender, and area of residence) using Mantel-Haenszel methods
For the evaluation of quality of life, specific analyses were conducted separately in groups based on sex and age. We then performed five tests adjusted by Bonferroni correction and the statistical significance was set at p = 0.01 with a bilateral formulation.
EpiData 3.1™ software (EpiData Association, Copenhagen, 2003) was used for data entry and Stata 10.0™ software (StataCorp. 2008, Texas, USA) for analysis.
During the SEROCHIK survey, which had received ethical approval, the participating subjects had been informed that they might be called back for ancillary research. During the telephone interview, the objectives of the study were presented and oral consent to participate was obtained. For people under the age of 18, the inform consent form was completed by parents.
We thank the team at the Centre for Clinical Investigations and Clinical Epidemiology of La Réunion and all subjects included in the SEROCHIK survey.
We are grateful to the population of La Réunion Island for being so co-operative.
We also wish to thank the technicians of the Centre d'Investigation Clinique - Épidémiologie Clinique of La Réunion who collected the sera samples, those of Groupe Hospitalier Sud - Réunion and Institut Pasteur laboratories who analyzed the sera, and all the persons who collectively contributed to strengthening the present paper.