Chikungunya and dengue viruses in travelers.

To the Editor: Chikungunya vires (CHIKV), an arthropod-borne virus transmitted to humans by Aedes spp. mosquitoes, was first isolated in Tanzania (Tanganyika) in 1953 (1). Various outbreaks have since occurred in Africa, Southeast Asia, and India (2).

CHIKV has recently been reported in a large area in the Indian Ocean islands and the Indian subcontinent. After an outbreak in Kenya in 2004, other outbreaks occurred in early 2005 on the Comoros Islands, Reunion, and other islands in the southwestern Indian Ocean; the epidemic then spread to India (3,4). Molecular analysis showed that the epidemic was caused by a variant of the Central/East African CHIKV genotype (5,6).

Internet surveillance networks provided information on epidemics in real time, alerting clinicians in the industrialized world to the spread of CHIKV and enabling them to more easily diagnose infection among travelers with fevers (7). We report results of diagnostic tests and analysis of predictors of infection among persons in Italy with symptoms suggestive of CHIKV infection who had traveled to potentially affected areas. Dengue virus (DENV) is endemic to many of these areas.

We studied travelers or migrants from areas to which CHIKV infection is endemic (i.e., sub-Saharan Africa) or areas currently affected by outbreaks (i.e., the Indian Ocean islands, India) who had symptoms suggestive of infection (i.e., fever and arthralgia with or without a rash) from January 2006 through March 2007. At least 1 blood sample was collected from each patient and stored at -80 [degrees]C before testing for CHIKV and DENV. Median lag between onset of symptoms and date of blood collection was 22 days (range 3-179 days). Two samples (acute phase and convalescence phase) were available from 5 patients. Serologic diagnosis of CHIKV infection was determined by hemagglutination inhibition (HI) test and confirmed by plaque-reduction neutralization test (8). Serodiagnosis of DENV infection was conducted by using the HI test and an immunoglobulin M ELISA (Focus Diagnostics, Cypress, CA, USA). A case-report form containing information about age, sex, countries visited, travel dates, and date of onset of symptoms was completed for each patient.

Seventy-six persons participated in the study; 55.3% were male, median age was 39 years (range 1-69 years), and most (80.3%) were Italian (Table). A total of 29 (38.2%) were positive for CHIKV, and 13 (17.1%) were positive for DENV; 34 (44.7%) were negative for both viruses. Of the 29 CHIKV-positive persons, 22 (75.9%) had visited the Indian Ocean islands (Mauritius, Reunion, and Madagascar), 5 had visited Asia, and 2 had visited Africa. Travelers from Indian Ocean islands had a higher risk for CHIKV infection than those who had visited Africa (odds ratio [OR] 11.0, 95% confidence interval [CI] 1.60-119.13) or Asia (OR 17.05, 95% CI 4.31-73.05). Persons who had visited Asia had a higher risk for DENV infection (OR 8.36; 95% CI 1.58-81.73) than those who had visited other areas.

The 5 persons who were infected with CHIKV in Asia had visited India (i.e., the most visited country [21 travelers]). However, persons who visited the Indian Ocean islands had a higher risk of being CHIKV positive than those who had visited India (OR 8.8, 95% CI 2.09-39.86). A rash was associated with CHIKV infection and was >8x more likely to be reported by CHIKV-positive persons than CHIKV-negative persons (OR 7.03, 95% CI 2.23-22.93). Moreover, rash was observed in 65% of CHIKV-positive cases and 31% of DENV-positive cases, but the difference was not statistically significant because of the small sample size (OR 4.28, 95% CI 0.88-23.23). None of the other patient's characteristics was associated with infection with CHIKV or DENV.

A limitation of our study was that only 5 patients had documented sero-conversion for CHIKV. However, high titers were found in all but 1 patient (>1,280 in 21 patients and 640 in 2 patients). This patient, who had a titer of 80, was an Italian who had probably not been previously exposed to CHIKV. Thus, the risk for misclassification was low. PCR for early detection of infection was not used because only 3 persons were tested within 10 days of symptom onset. Two of these persons, who were tested 7 days after symptom onset, already had antibodies to CHIKV.

In conclusion, a high proportion of travelers with symptoms of CHIKV infection who returned from areas with outbreaks of this infection or where this virus was endemic were seropositive. A lower proportion of patients had antibodies to DENV. CHIKV-positive patients were more likely to have a rash than those negative for both CHIKV and DENV. As suggested by previous studies (9), a rash was more common among CHIKV-positive patients than in DENV-infected patients, but the difference was not significant. Our study suggests that identification of predictors of infection with CHIKV is feasible, although it is complicated by cocirculation of DENV in the same areas.

References

(1.) Ross RW. The Newala epidemic. III. The virus: isolation, pathogenic properties and relationship to the epidemic. J Hyg (Lond). 1956;54:177-91.

(2.) Pialoux G, Gauzere B-A, Jaureguiberry S, Strobel M. Chikungunya, an epidemic arbovirosis. Lancet Infect Dis. 2007;7: 319-27.

(3.) World Health Organization. Chikungunya and dengue, south-west Indian Ocean. Wkly Epidemiol Rec. 2006;81 : 105-16.

(4.) Charrel RN, de Lamballerie X, Raoult D. Chikungunya outbreaks-the globalization of vectorbome diseases. N Engl J Med. 2007;356:769-71.

(5.) Yergolkar PN, Tandale BV, Arankalle VA, Sathe PS, Sudeep AB, Gandhe SS, et al. Chikungunya outbreaks caused by African genotype, India. Emerg Infect Dis. 2006;12:1580-3.

(6.) Parola P, de Lamballerie X, Jourdan J, Rovery C, Vaillant V, Minodier P, et al. Novel chikungunya virus variant in travelers returning from Indian Ocean islands. Emerg Infect Dis. 2006; 12:1493-9.

(7.) Mourya DT, Mishra AC. Chikungunya fever. Lancet. 2006;368:186-7.

(8.) Peragallo MS, Nicoletti L, Lista F, D'Amelio R; East Timor Dengue Study Group. Probable dengue virus infection among Italian troops, East Timor, 1999-2000. Emerg Infect Dis. 2003;9:876-80.

(9.) Wichmann O, Gascon J; Schunk M, Puente S, Sikamaki H, Giorup I, et al. Severe dengue virus infection in travelers: risk factors and laboratory indicators. J Infect Dis. 2007;195:1089-96.

Loredana Nicoletti, * Massimo Ciccozzi, * Antonella Marchi, * Cristiano Fiorentini, * Patrizia Martucci, * Fortunato D'Ancona, * Marta Ciofi degli Atti, * Maria Grazia Pompa, (([dagger])) Giovanni Rezza, * and Maria Grazia Ciufolini *

* Istituto Superiore di Sanita Rome, Italy; and (([dagger])) Ministero della Salute, Rome, Italy

Address for correspondence: Giovanni Rezza, Department of Infectious Diseases, Epidemiology Unit, Istituto Superiore di Sanita, Viale Regina Elena 299, Rome 00161, Italy; email: [e-mail]

Table. Characteristics of 76 travelers studied

                     Chikungunya
                       virus-      Dengue virus-
                      positive,      positive,     Seronegative,
Characteristic         no. (%)        no. (%)         no. (%)

Total                 29 (100.0)    13 (100.0)       34 (100.0)
Sex
  Male                17 (58.6)      6 (46.2)        19 (55.9)
  Female              12 (41.4)      7 (53.8)        15 (44.1)
Age, y
  0-35                 8 (27.6)      4 (30.8)        16 (47.0)
  36-50               11 (37.9)      6 (46.1)        14 (41.2)
  >50                 10 (34.5)      3 (23.1)         4 (11.8)
Days spent abroad
  0-15                18 (62.1)      4 (30.8)        20 (58.8)
  >15                 11 (37.9)      9 (69.2)        14 (41.2)
Area visited *
  Africa               2 (6.9)       2 (15.4)         6 (17.6)
  African islands     22 (75.9)          0            8 (23.5)
  Asia                 5 (17.2)     11 (84.6)        20 (58.8)
Nationality
  Italian             23 (79.3)      9 (69.2)        29 (85.3)
  Other                6 (20.7)      4 (30.8)         5 (14.7)
Rash
  Yes                 19 (65.5)      4 (30.8)         6 (17.6)
  No                  10 (34.5)      9 (69.2)        28 (82.3)

* Africa, continental Africa; African Islands, Western Indian Ocean
islands; Asia, India and Southeast Asia.