5%), Thailand (35.5%), India (10.3%), Malaysia see more (3.7%), Tanzania (3.7%), South Africa (3.7%), Sri Lanka (2.8%), Mozambique (1.9%), Australia (1.9%), and Malawi, Dubai, Mauritius, Kenya, Singapore, Oman, Bahrain, Iran, and United Arab Emirates (all 0.9%). Twenty-two patients had traveled in 2007, 39 in 2008, 23 in 2009, and 23 patients in 2010. Antibodies to CHIKV were detected in sera of eight travelers (7.5%; Table 1). Seven patients had clear evidence of recent infection

(6.5%), based on both IgM- and IgG-positive serology (n = 5), or IgM serology confirmed by PCR and/or NT (n = 2). A second serum sample of one of the two IgM-positive patients showed seroconversion for IgG. One traveler was only IgG positive at a single time point 25 days upon return from the Indian Ocean area. As CHIKV IgM are typically lasting up to 3 months postinfection, this patient probably had prior exposure to CHIKV unrelated to the current complaints for which DENV diagnostics were requested. Of the seven travelers with chikungunya, three had visited Thailand, one had a history of travel to both Thailand and Malaysia, two had traveled to Indonesia, and one to India (Table 1). In total, 6.3% of the male patients and 9.1% 26s Proteasome structure of the female patients of the cohort showed evidence of a CHIKV infection. The neutralization assay confirmed the presence of CHIKV-specific antibodies in sera of four out of four patients with acute symptoms. For five seropositive

travelers, the remaining amount of serum was insufficient to perform a NT (data not shown). This study demonstrates Sitaxentan that in the Netherlands CHIKV infections were substantially underdiagnosed in travelers suspected of dengue

and returning from the Indian Ocean area in the period 2007 to 2010. In 6.5% of the travelers with negative DENV serology, CHIKV appeared to be the etiologic agent. For comparison, of the total of 158 travelers to this region for whom DENV diagnostics were requested, 25.9% showed a positive serology for DENV IgM and/or IgG. As coinfections of humans with DENV and CHIKV have been described, the results of this study potentially underestimate the number of CHIKV cases. Some of the DENV positives could have been coinfected with CHIKV.[2] An analysis of air passenger traffic from CHIKV hotspots to Europe resulted in an estimated annual number of 1,302 viremic travelers from India and Malaysia to the Netherlands,[9] supporting our observation that CHIKV infections are underdiagnosed in the Netherlands as only three CHIKV infections were diagnosed in our laboratory in the period 2009 to 2011 (data not shown). Recently, a similar observation of underdiagnosis was described for Germany.[10] Although infections with DENV or CHIKV are both typified by fever, myalgia, and rash, and the reported incubation periods are similar (4–7 d for DENV, range 3–14 d; 3–7 d for CHIKV, range 1–12 d), other clinical features are clearly different.