Zika Virus Antibody Titers Three Years after Confirmed Infection.

BACKGROUND: In 2015-2016, a large Zika virus (ZIKV) outbreak occurred in the Americas. Although the exact ZIKV antibody kinetics after infection are unknown, recent evidence indicates the rapid waning of ZIKV antibodies in humans. Therefore, we aimed to determine the levels of ZIKV antibodies more than three years after a ZIKV infection. METHODS: We performed ZIKV virus neutralization tests (VNT) and a commercial ZIKV non-structural protein 1 (NS1) IgG ELISA in a cohort of 49 participants from Suriname who had a polymerase-chain-reaction-confirmed ZIKV infection more than three years ago. Furthermore, we determined the presence of antibodies against multiple dengue virus (DENV) antigens. RESULTS: The ZIKV seroprevalence in this cohort, assessed with ZIKV VNT and ZIKV NS1 IgG ELISA, was 59.2% and 63.3%, respectively. There was, however, no correlation between these two tests. Furthermore, we did not find evidence of a potential negative influence of DENV immunity on ZIKV antibody titers. CONCLUSIONS: ZIKV seroprevalence, assessed with two commonly used serological tests, was lower than expected in this cohort of participants who had a confirmed previous ZIKV infection. This can have implications for future ZIKV seroprevalence studies and possibly for the duration of immunological protection after a ZIKV infection.

Guillain-Barré Syndrome in Suriname; Clinical Presentation and Identification of Preceding Infections.

Guillain-Barré syndrome (GBS) is associated with various types of preceding infections including Campylobacter jejuni and cytomegalovirus, but there is also an association with arthropod borne viruses (arboviruses), such as Zika virus, that are endemic in tropical regions. Here we present the clinical characteristics of 12 GBS patients from Suriname that were hospitalized between the beginning of 2016 and half 2018. Extensive diagnostic testing was performed for pathogens that are commonly associated with GBS, but also for arboviruses, in order to identify the preceding infection that might have led to GBS. With this extensive testing algorithm, we could identify a recent infection in six patients of which four of them had evidence of a recent Zika virus or dengue virus infection. These results suggest that arboviruses, specifically Zika virus but possibly also dengue virus, might be important causative agents of GBS in Suriname. Furthermore, we found that more accessibility of intravenous immunoglobulins or plasma exchange could improve the treatment of GBS in Suriname.

Shedding of Yellow Fever Virus From an Imported Case in the Netherlands After Travel to Brazil.

We report yellow fever infection in a Dutch traveler returning from Brazil. Yellow fever virus (YFV) was identified in serum and urine samples over a period of 1 month. Yellow fever virus genome sequences from the patient clustered with recent Brazilian YFV and showed with limited nucleotide changes during the resolving infection.

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: the ZIKAlliance consortium.

BACKGROUND: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. METHODS: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmission clustering, disabilities and health economics, viral kinetics, the potential role of antibody enhancement, and co-infections will be linked to the cohort studies. DISCUSSION: Results of these large cohort studies will provide better risk estimates for birth defects and other developmental abnormalities associated with ZIKV infection including possible co-factors for the variability of risk estimates between other countries and regions. Additional outcomes include incidence and transmission estimates of ZIKV during and after pregnancy, characterization of short and long-term clinical course following infection and viral kinetics of ZIKV. STUDY REGISTRATIONS: clinicaltrials.gov NCT03188731 (PW cohort), June 15, 2017; clinicaltrials.gov NCT03393286 (CH cohort), January 8, 2018; clinicaltrials.gov NCT03204409 (NH cohort), July 2, 2017.

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.

Global monitoring of antimicrobial resistance based on metagenomics analyses of urban sewage.

Antimicrobial resistance (AMR) is a serious threat to global public health, but obtaining representative data on AMR for healthy human populations is difficult. Here, we use metagenomic analysis of untreated sewage to characterize the bacterial resistome from 79 sites in 60 countries. We find systematic differences in abundance and diversity of AMR genes between Europe/North-America/Oceania and Africa/Asia/South-America. Antimicrobial use data and bacterial taxonomy only explains a minor part of the AMR variation that we observe. We find no evidence for cross-selection between antimicrobial classes, or for effect of air travel between sites. However, AMR gene abundance strongly correlates with socio-economic, health and environmental factors, which we use to predict AMR gene abundances in all countries in the world. Our findings suggest that global AMR gene diversity and abundance vary by region, and that improving sanitation and health could potentially limit the global burden of AMR. We propose metagenomic analysis of sewage as an ethically acceptable and economically feasible approach for continuous global surveillance and prediction of AMR.

Zika Virus Seroprevalence in Urban and Rural Areas of Suriname, 2017.

In 2015-2016, a Zika virus (ZIKV) outbreak occurred in the Americas. In 2017, we conducted a ZIKV serosurvey in Suriname in which 770 participants were recruited from 1 urban area and 2 rural villages in the tropical rainforest. All collected samples were tested for presence of ZIKV antibodies using a ZIKV immunoglobulin G enzyme-linked immunosorbent assay and a virus neutralization assay. We found that 35.1% of the participants had neutralizing antibodies against ZIKV. In 1 remote village in the rainforest, 24.5% of the participants had neutralizing antibodies against ZIKV, suggesting that ZIKV was widely spread across Suriname.

Re-evaluation of routine dengue virus serology in travelers in the era of Zika virus emergence.

BACKGROUND: Diagnostic requests for both Zika virus (ZIKV) and dengue virus (DENV) infections in returning travelers have significantly increased during the recent ZIKV outbreak in the Americás. These flaviviruses have overlapping clinical syndromes and geographical distribution, but diagnostic differentiation is important because of different clinical consequences. As flaviviruses are known to have a short viremic period, diagnostics often rely on serological methods, which are challenging due to extensive cross-reactive antibodies. OBJECTIVE: To re-evaluate the performance of DENV serological assays in laboratory confirmed ZIKV-infected travelers. STUDY DESIGN: The extent of cross-reactivity of the DENV NS1 antigen, IgM and IgG ELISA was analyzed in 152 clinical blood samples collected from 69 qRT-PCR and 24 virus neutralization titer (VNT) confirmed ZIKV-infected travelers. RESULTS: The majority of travelers in the presented cohort returned to the Netherlands from Suriname and presented with symptoms of fever and rash. Twenty-three percent of the female travelers were pregnant. None of the 39 ZIKV RNA positive blood samples were cross-reactive in the DENV NS1 antigen ELISA. The rates of cross-reactivity of the DENV IgM and IgG ELISÁs were 31% and 54%, respectively, after excluding travelers with (potential) previous DENV exposure. CONCLUSIONS: Although the DENV NS1 antigen assay was highly specific in this cohort of laboratory confirmed ZIKV-infected travelers, we demonstrate high percentages of cross-reactivity of DENV IgM and IgG ELISÁs of which diagnostic laboratories should be aware. In addition, the high rate of DENV IgG background of >25% complicates a proper serological diagnosis in this group.

Yellow fever in a traveller returning from Suriname to the Netherlands, March 2017.

A Dutch traveller returning from Suriname in early March 2017, presented with fever and severe acute liver injury. Yellow fever was diagnosed by (q)RT-PCR and sequencing. During hospital stay, the patient's condition deteriorated and she developed hepatic encephalopathy requiring transfer to the intensive care. Although yellow fever has not been reported in the last four decades in Suriname, vaccination is recommended by the World Health Organization for visitors to this country.

Longitudinal follow-up of Zika virus RNA in semen of a traveller returning from Barbados to the Netherlands with Zika virus disease, March 2016.

We report the longitudinal follow-up of Zika virus (ZIKV) RNA in semen of a traveller who developed ZIKV disease after return to the Netherlands from Barbados, March 2016. Persistence of ZIKV RNA in blood, urine, saliva and semen was followed until the loads reached undetectable levels. RNA levels were higher in semen than in other sample types and declined to undetectable level at day 62 post onset of symptoms.

Longitudinal follow-up of Zika virus RNA in semen of a traveller returning from Barbados to the Netherlands with Zika virus disease, March 2016

We report the longitudinal follow-up of Zika virus (ZIKV) RNA in semen of a traveller who developed ZIKV disease after return to the Netherlands from Barbados, March 2016. Persistence of ZIKV RNA in blood, urine, saliva and semen was followed until the loads reached undetectable levels. RNA levels were higher in semen than in other sample types and declined to undetectable level at day 62 post onset of symptoms...(AU)

Zika virus infection in 18 travellers returning from Surinam and the Dominican Republic, The Netherlands, November 2015-March 2016.

PURPOSE: We report 18 cases of confirmed Zika virus (ZIKV) infection in travellers returning to the Netherlands from Surinam (South America, bordering northern Brazil) and the Dominican Republic. METHODS: In a multi-centre study, we collected epidemiological, virological and clinical characteristics, as well as data on travel history, underlying illness and laboratory results of the 18 imported ZIKV infection cases using a standardised form. RESULTS: Most cases had a self-limiting course of disease, two patients developed complications, one had Guillain-Barré and another had severe thrombocytopenia. Four patients had underlying illness. One of the reported cases was pregnant. Three of 13 patients tested had a weak-positive result for dengue IgM. The majority of patients were born in Suriname and/or visiting friends and relatives (VFR). CONCLUSIONS: Providing pre-travel advice among travellers, especially VFR travellers, is needed to enhance the use of preventive measures against ZIKV infection. Further evidence on health risks associated with ZIKV infection is urgently needed.

International linkage of two food-borne hepatitis A clusters through traceback of mussels, the Netherlands, 2012.

This report describes an outbreak investigation starting with two closely related suspected food-borne clusters of Dutch hepatitis A cases, nine primary cases in total, with an unknown source in the Netherlands. The hepatitis A virus (HAV) genotype IA sequences of both clusters were highly similar (459/460 nt) and were not reported earlier. Food questionnaires and a case-control study revealed an association with consumption of mussels. Analysis of mussel supply chains identified the most likely production area. International enquiries led to identification of a cluster of patients near this production area with identical HAV sequences with onsets predating the first Dutch cluster of cases. The most likely source for this cluster was a case who returned from an endemic area in Central America, and a subsequent household cluster from which treated domestic sewage was discharged into the suspected mussel production area. Notably, mussels from this area were also consumed by a separate case in the United Kingdom sharing an identical strain with the second Dutch cluster. In conclusion, a small number of patients in a non-endemic area led to geographically dispersed hepatitis A outbreaks with food as vehicle. This link would have gone unnoticed without sequence analyses and international collaboration.

Zika Virus Infection and Guillain-Barré Syndrome in Three Patients from Suriname.

We present three patients from Suriname who were diagnosed with Guillain-Barré syndrome (GBS) during the Zika virus (ZIKV) outbreak in this country. One patient had a positive ZIKV urine real-time RT-PCR (qRT-PCR) result. The other two patients had a negative ZIKV urine qRT-PCR but a positive virus neutralization test and presence of IgG antibodies against ZIKV in the serum. Considering the evidence of a past ZIKV infection and absence of evidence for recent infections with the most common preceding infections of GBS, it is very likely that these GBS cases were triggered by ZIKV.