West Nile Virus RNA Not Detected in Urine of 40 People Tested 6 Years After Acute West Nile Virus Disease

Gibney, Katherine B; Lanciotti, Robert S.; Sejvar, James J.; Nugent, C. Thomas; Linnen, Jeffrey M.; Delorey, Mark J.; Lehman, Jennifer; Boswell, Erin N.; Staples, J. Erin; Fischer, Marc

doi:10.1093/infdis/jiq057

Cited by 54 publications

(30 citation statements)

References 14 publications

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“…This has been suggested by viral RNA detection in human whole blood out to 90 days postinfection, nucleic acids in tissues in a mouse model out to 6 months, and RNA detection in urine from previously infected humans out to 6 years (16)(17)(18). However, others have not been able to verify the latter finding (19).…”

Section: Discussionmentioning

confidence: 99%

Characteristics of Antibody Responses in West Nile Virus-Seropositive Blood Donors

Carson

Prince²,

Biggerstaff

et al. 2014

J Clin Microbiol

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The production of WNV-specific IgM and IgG antibodies is important for both the diagnosis and the clearance of WNV infection (4). The persistence of IgG antibodies is thought to confer protection from subsequent reinfection (4-6). In a study of 245 viremic blood donors, IgM antibodies persisted for a mean of 156 days, and IgG antibodies persisted at the same titer for at least 1 year postinfection (7). IgM antibodies persisted in up to 17% of subjects at 400 days postinfection, whereas IgG antibodies were maintained at high levels based on enzyme immunoassay (EIA) signal-to-cutoff levels among all subjects. It is unclear if antibodies persist beyond that time, if those antibodies are specific for and neutralize WNV, and if antibody responses and persistence vary depending on age or sex.We studied the characteristics of WNV antibody responses in two different groups of blood donors, one identified by a crosssectional serosurvey and the second by a longitudinal follow-up of donors detected during acute viremia by blood donor screening for WNV RNA. We compared the antibody levels in donors with recent versus more remote infections and looked at differences according to age and sex. We also assessed the specificity and neutralizing capacities of the antibody responses. MATERIALS AND METHODSThis study was approved by the institutional review boards of the participating institutions, and all subjects agreed to participate and signed informed consents. Blood donors who were seropositive for WNV IgG antibodies were identified from a previously reported serosurvey of Ͼ4,500 North Dakota blood donors (2). In that study, 370 donors (8.2%) were IgG positive, and 28 of those (7.5%) were also IgM positive. The durability of the antibody responses was assessed by comparing IgG antibody levels among recently infected donors (those who were IgM seropositive) versus donors presumed to be infected Ͼ1 year prior (i.e., were IgM negative). The specificity and neutralizing capacity of the antibody response were assessed by assaying a subset (54 samples across the range of IgG response) of samples from seropositive donors using a WNV plaque reduction neutralization assay to quantify plaque reduction neutralization titers. These samples were selected by choosing every 6th sample from the lowest to highest titers across the IgG response spectrum from 324 samples with adequate volume remaining for plaque reduction neutralization testing (PRNT).We also studied a group of 18 donors who were originally identified with acute WNV infection by screening for blood plasma RNA with nucleic acid amplification technology (NAT) in 2005 and who were enrolled in a 1-year longitudinal follow-up study (7). Their WNV IgG, IgM, and PRNT levels were assessed at 6 months and 5 years postinfection. These samples were tested in parallel and under code to minimize interrun variability and biases in assay performance and interpretation.Blood plasma specimens were tested for WNV IgM and IgG by using Food and Drug Administration-approved enzyme-linked immunosorb...

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Section: Discussionmentioning

confidence: 99%

Characteristics of Antibody Responses in West Nile Virus-Seropositive Blood Donors

Carson

Prince²,

Biggerstaff

et al. 2014

J Clin Microbiol

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“…In addition, in some cases convalescent patients may have persistent or chronic infection detected through PCR of the urine, which suggested ongoing viral replication in renal tissue (141,143). Although persistence of WNV has also been noted in several animal models (156,199,213), it has not been uniformly evident in assays of urine (66).…”

Section: Mammalian Infection Epidemiology and Clinical Featuresmentioning

confidence: 99%

West Nile Virus: Biology, Transmission, and Human Infection

et al. 2012

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“…In one study, WNV RNA was detected in a subset of patients with persistent symptoms 1-7 years post WNV infection [90]. However, in a separate study of WNV patients >6 years post infection, WNV RNA was not detected in the urine [91, 92]. However, a recent study showed that high levels of WNV RNA could be amplified in urine during acute infection and up to 30 days after presentation [93].…”

Section: Controversies In Virus Persistence and Immune Responsesmentioning

confidence: 99%

Of Mice and Men: Protective and Pathogenic Immune Responses to West Nile Virus Infection

Trobaugh

Green

2015

Curr Trop Med Rep

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West Nile virus, a mosquito-borne flavivirus, first emerged in the Western Hemisphere in 1999. Although the majority of infections are asymptomatic, WNV causes significant morbidity and mortality in a minority of individuals who develop neuroinvasive disease, in particular the elderly and immunocompromised. Research in animal models has demonstrated interactions between WNV and the innate and adaptive immune system, some of which protect the host and others which are deleterious. Studies of disease pathogenesis in humans are less numerous, largely due to the complexities of WNV epidemiology. Human studies that have been done support the notion that innate and adaptive immune responses are delicately balanced and may help or harm the host. Further human investigations are needed to characterize beneficial responses to WNV with the goal of such research leading to therapeutics and effective vaccines in order to control this emerging viral disease.

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West Nile Virus RNA Not Detected in Urine of 40 People Tested 6 Years After Acute West Nile Virus Disease

Cited by 54 publications

References 14 publications

Characteristics of Antibody Responses in West Nile Virus-Seropositive Blood Donors

Characteristics of Antibody Responses in West Nile Virus-Seropositive Blood Donors

West Nile Virus: Biology, Transmission, and Human Infection

Of Mice and Men: Protective and Pathogenic Immune Responses to West Nile Virus Infection

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