Genetic and Serologic Properties of Zika Virus Associated with an Epidemic, Yap State, Micronesia, 2007

One-sentence summary for table of contents: The full coding region nucleic acid sequence and serologic properties of the virus were identified

Transmission of Yellow Fever Vaccine Virus Through Blood Transfusion and Organ Transplantation in the USA in 2021: Report of an Investigation

BACKGROUND: In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients. METHODS: From Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by the organ donor. FINDINGS: We identified one read from yellow fever virus in cerebrospinal fluid from the recipient of a kidney using metagenomic next-generation sequencing. Recent infection with yellow fever virus was confirmed in all four organ recipients by identification of yellow fever virus RNA consistent with the 17D vaccine strain in brain tissue from one recipient and seroconversion after transplantation in three recipients. Two patients recovered and two patients had no neurological recovery and died. 3 days before organ procurement, the organ donor received a blood transfusion from a donor who had received a yellow fever vaccine 6 days before blood donation. INTERPRETATION: This investigation substantiates the use of metagenomic next-generation sequencing for the broad-based detection of rare or unexpected pathogens. Health-care workers providing vaccinations should inform patients of the need to defer blood donation for at least 2 weeks after receiving a yellow fever vaccine. Despite mitigation strategies and safety interventions, a low risk of transfusion-transmitted infections remains. FUNDING: US Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority, and the CDC Epidemiology and Laboratory Capacity Cooperative Agreement for Infectious Diseases

Chikungunya Virus in US Travelers Returning from India, 2006

Chikungunya virus (CHIKV), a mosquitoborne alphavirus; is endemic in Africa and Asia. In 2005–2006, CHIKV epidemics were reported in islands in the Indian Ocean and in southern India. We present data on laboratory-confirmed CHIKV infections among travelers returning from India to the United States during 2006

Fatal Human Infection with Evidence of Intrahost Variation of Eastern Equine Encephalitis Virus, Alabama, USA, 2019

Eastern equine encephalitis virus (EEEV) is an arbovirus in the family Togaviridae, genus Alphavirus, found in North America and associated with freshwater/hardwood swamps in the Atlantic, Gulf Coast, and Great Lakes regions. EEEV disease in humans is rare but causes substantial illness and death. To investigate the molecular epidemiology and microevolution of EEEV from a fatal case in Alabama, USA, in 2019, we used next-generation sequencing of serum and cerebrospinal fluid (CSF). Phylogenetic inference indicated that the infecting strain may be closely related to isolates from Florida detected during 2010–2014, suggesting potential seeding from Florida. EEEV detected in serum displayed a higher degree of variability with more single-nucleotide variants than that detected in the CSF. These data refine our knowledge of EEEV molecular epidemiologic dynamics in the Gulf Coast region and demonstrate potential quasispecies bottlenecking within the central nervous system of a human host

Multiplex Microsphere Immunoassays for the Detection of IgM and IgG to Arboviral Diseases

<div><p>Serodiagnosis of arthropod-borne viruses (arboviruses) at the Division of Vector-Borne Diseases, CDC, employs a combination of individual enzyme-linked immunosorbent assays and microsphere immunoassays (MIAs) to test for IgM and IgG, followed by confirmatory plaque-reduction neutralization tests. Based upon the geographic origin of a sample, it may be tested concurrently for multiple arboviruses, which can be a cumbersome task. The advent of multiplexing represents an opportunity to streamline these types of assays; however, because serologic cross-reactivity of the arboviral antigens often confounds results, it is of interest to employ data analysis methods that address this issue. Here, we constructed 13-virus multiplexed IgM and IgG MIAs that included internal and external controls, based upon the Luminex platform. Results from samples tested using these methods were analyzed using 8 different statistical schemes to identify the best way to classify the data. Geographic batteries were also devised to serve as a more practical diagnostic format, and further samples were tested using the abbreviated multiplexes. Comparative error rates for the classification schemes identified a specific boosting method based on logistic regression “Logitboost” as the classification method of choice. When the data from all samples tested were combined into one set, error rates from the multiplex IgM and IgG MIAs were <5% for all geographic batteries. This work represents both the most comprehensive, validated multiplexing method for arboviruses to date, and also the most systematic attempt to determine the most useful classification method for use with these types of serologic tests.</p> </div

True classification vs. test value – IgM based on V/N.

<p>True classification (y-axis) refers to the original diagnostic result based on the traditional screening method plus plaque reduction neutralization, and test value (x-axis) is the V/N measurement for each sample. Samples in each set used in the analyses are depicted: black dots represent the initial set; red dots represent the geographic validation set; blue dots represent the summer 2011 set. Sample rows for the infecting virus are shaded grey in each antigen panel.</p

Map depicting the areas covered and viruses tested for in the 3 multiplex MIA geographic batteries.

<p>US covers the US and Canada; CSAM covers Central and South America and the Caribbean; AAE covers Asia, Europe and Africa. Australia and parts of the South Pacific are not included in the multiplex batteries.</p

Error rates (%) for full data classification.

<p>Error rates (y-axes) where 1.0 is 100% incorrect classification (i.e. includes false positives and false negatives) are shown for the combined data set comprising the initial, geographic and summer 2011 sample sets. Error rates are shown for the 2 best classification options, multinomial linear regression (Multi) and logitboost (logit) on the x-axes. Full and test error rates are described in the analysis section of Materials and Methods. Logit. tie right/tie wrong is where the results that are tied are included in the error rates as being right or wrong. Logit. iteration is where more iterations of the classification scheme are performed than normally would be (usually equal to the number of data points in the set). This results in increased error rates due to over-fitting of the data such that any sample variation outside of the limits of the sample set used for deriving the classification rules results in an error.</p

Yap Main Island and Yap State, Federated States of Micronesia.

<p>Yap Main Island and Yap State, Federated States of Micronesia.</p