Characterization of antibody response in patients with acute and chronic chikungunya virus disease.

BACKGROUND: Chikungunya virus (CHIKV) is a re-emerging arbovirus capable of causing chronic arthralgia, which can last for months to years. Although neutralizing antibodies have been shown to be important for viral clearance, is it not clear whether the quantitative and qualitative nature of antibodies play a role in progression to chronic disease. OBJECTIVES: To characterize and compare the antibody responses in acute and chronic patients in a prospective observational CHIKV study in Curaçao during the 2014-2015 outbreak. STUDY DESIGN: We performed virus neutralization tests and ELISA on plasma samples collected from a prospective observational chikungunya study in Curaçao to compare the complement-dependent and -independent neutralization capacity, as well as the antibody avidity index of acute and chronic patients. RESULTS: We found that there was no significant difference in the virus neutralization titers between patients with acute and chronic chikungunya infection. Furthermore, we found that complement increased the neutralization capacity when large amounts of virus was used. Moreover, we found that patients with acute chikungunya disease had a significantly higher antibody avidity index compared to those with chronic disease. CONCLUSIONS: This study suggests that virus neutralization titers in late convalescent sera do not play a role in chronic chikungunya. However, the median antibody avidity was lower in these patients and may therefore suggest a role for antibody avidity in the development of chronic disease.

Zika Virus Outbreak on Curaçao and Bonaire, a Report Based on Laboratory Diagnostics Data.

Background: Zika virus (ZIKV) emerged in May 2015 in Brazil, from which it spread to many other countries in Latin America. Cases of ZIKV infection were eventually also reported in Curaçao (January 2016) and Bonaire (February 2016). Methods: In the period of 16 December 2015 until 26 April 2017, serum, EDTA-plasma or urine samples were taken at Medical Laboratory Services (MLS) from patients on Curaçao and tested in qRT-PCR at the Erasmus Medical Centre (EMC) in the Netherlands. Between 17 October 2016 until 26 April 2017 all samples of suspected ZIKV-patients collected on Curaçao, as well as on Bonaire, were tested at MLS. Paired urine and/or serum samples from patients were analyzed for ZIKV shedding kinetics, and compared in terms of sensitivity for ZIKV RNA detection. Furthermore, the age and gender of patients were used to determine ZIKV incidence rates, and their geozone location to determine the spatial distribution of ZIKV cases. Results: In total, 781 patients of 2820 tested individuals were found qRT-PCR-positive for ZIKV on Curaçao. The first two ZIKV cases were diagnosed in December 2015. A total of 112 patients of 382 individuals tested qRT-PCR-positive for ZIKV on Bonaire. For both islands, the peak number of absolute cases occurred in November 2016, with 247 qRT-PCR confirmed cases on Curaçao and 66 qRT-PCR-positive cases on Bonaire. Overall, a higher proportion of women than men was diagnosed with ZIKV on both islands, as well as mostly individuals in the age category of 25-54 years old. Furthermore, ZIKV cases were mostly clustered in the east of the island, in Willemstad. Conclusions: ZIKV cases confirmed by qRT-PCR indicate that the virus was circulating on Curaçao between at least December 2015 and March 2017, and on Bonaire between at least October 2016 and February 2017, with peak cases occurring in November 2016. The lack of preparedness of Curaçao for the ZIKV outbreak was compensated by shipping all samples to the EMC for diagnostic testing; however, both islands will need to put the right infrastructure in place to enable a rapid response to an outbreak of any new emergent virus in the future.

Hyperferritinemia is a potential marker of chronic chikungunya: A retrospective study on the Island of Curaçao during the 2014-2015 outbreak.

BACKGROUND: Recently Chikungunya virus (CHIKV) outbreaks have been reported in the Carribean. There is no data regarding the outbreak in Curaçao. In addition, to date there is no biomarker that could be used to predict chronic infection. OBJECTIVES: To characterize the first CHIKV outbreak in Curaçao and to identify potential biomarkers for chronic infection. STUDY DESIGN: A serological test and quantitative polymerase chain reaction (qPCR) were used on samples collected in Curaçao to confirm infection. Subsequently, six samples with high viral load were selected for phylogenetic analysis. Furthermore we investigated the association of macrophage-related biomarkers during CHIKV infection with chronic arthralgia/arthritis. RESULTS: 116 patients in Curacao were diagnosed with CHIKV infection based on ELISA and 77% were tested positive for CHIKV by qPCR. Phylogenetic analysis showed that an Asian genotype was the cause of the outbreak. Elevated levels of ferritin and CRP were significantly associated with viraemia. In addition, elevated ferritin levels were significantly associated with chronic arthralgia. CONCLUSIONS: The results showed that the presence of an Asian genotype of CHIKV in Curaçao for the first time. Moreover, we found an association between ferritin levels with chronic arthralgia.