Kui Gao

Failure to confirm XMRV/MLVs in the blood of patients with chronic fatigue syndrome: a multi-laboratory study.

The assays used to detect XMRV in patients with chronic fatigue syndrome are unreliable. Murine leukemia viruses (MLVs), including xenotropic-MLV–related virus (XMRV), have been controversially linked to chronic fatigue syndrome (CFS). To explore this issue in greater depth, we compiled coded replicate samples of blood from 15 subjects previously reported to be XMRV/MLV–positive (14 with CFS) and from 15 healthy donors previously determined to be negative for the viruses. These samples were distributed in a blinded fashion to nine laboratories, which performed assays designed to detect XMRV/MLV nucleic acid, virus replication, and antibody. Only two laboratories reported evidence of XMRV/MLVs; however, replicate sample results showed disagreement, and reactivity was similar among CFS subjects and negative controls. These results indicate that current assays do not reproducibly detect XMRV/MLV in blood samples and that blood donor screening is not warranted.

Zika Virus Tissue and Blood Compartmentalization in Acute Infection of Rhesus Macaques.

Animal models of Zika virus (ZIKV) are needed to better understand tropism and pathogenesis and to test candidate vaccines and therapies to curtail the pandemic. Humans and rhesus macaques possess similar fetal development and placental biology that is not shared between humans and rodents. We inoculated 2 non-pregnant rhesus macaques with a 2015 Brazilian ZIKV strain. Consistent with most human infections, the animals experienced no clinical disease but developed short-lived plasma viremias that cleared as neutralizing antibody developed. In 1 animal, viral RNA (vRNA) could be detected longer in whole blood than in plasma. Despite no major histopathologic changes, many adult tissues contained vRNA 14 days post-infection with highest levels in hemolymphatic tissues. These observations warrant further studies to investigate ZIKV persistence and its potential clinical implications for transmission via blood products or tissue and organ transplants.

First cases of Zika virus–infected US blood donors outside states with areas of active transmission

Zika virus (ZIKV) is transmitted by Aedes mosquitos and can result in severe congenital and adult neurologic abnormalities. ZIKV has rapidly spread northward through Central America and the Caribbean and autochthonous cases have been identified in the continental United States. High rates of ZIKA RNA positivity were detected in blood donors during previous epidemics. ZIKV transmission by transfused blood from healthy donor components has been a growing concern.

Xenotropic murine leukemia virus–related virus does not pose a risk to blood recipient safety

BACKGROUND: When xenotropic murine leukemia virus–related virus (XMRV) was first reported in association with chronic fatigue syndrome, it was suggested that it might offer a risk to blood safety. Thus, the prevalence of the virus among blood donors and, if present, its transmissibility by transfusion need to be defined.

Real-Time Evolution of Zika Virus Disease Outbreak, Roatán, Honduras

A Zika virus disease outbreak occurred in Roatán, Honduras, during September 2015–July 2016. Blood samples and clinical information were obtained from 183 patients given a clinical diagnosis of suspected dengue virus infection. A total of 79 patients were positive for Zika virus, 13 for chikungunya virus, and 6 for dengue virus.

Investigational Testing for Zika Virus among U.S. Blood Donors

Background Because of the potential severe clinical consequences of Zika virus (ZIKV) infection, the large numbers of asymptomatic travelers returning from ZIKV‐active areas, the detection of ZIKV nucleic acid in blood, and reports of transmission of ZIKV through transfusion, in 2016 the Food and Drug Administration released recommendations for individual‐unit nucleic acid testing to minimize the risk of transmission of ZIKV through blood transfusions. Methods The American Red Cross implemented investigational screening of donated blood for ZIKV RNA by means of transcription‐mediated amplification (TMA). Confirmatory testing of reactive donations involved repeat TMA, TMA testing in exploratory minipools, real‐time reverse‐transcriptase polymerase chain reaction, IgM serologic testing, and red‐cell TMA. Viral loads in plasma and red cells were estimated by means of end‐point TMA. The costs of interdicting a donation that was confirmed to be positive were calculated for the 15‐month period between June 2016 and September 2017. Results Of the 4,325,889 donations that were screened, 393,713 (9%) were initially tested in 24,611 minipools, and no reactive donations were found. Of the 3,932,176 donations that were subsequently tested individually, 160 were initially reactive and 9 were confirmed positive (a 1:480,654 confirmed‐positive rate overall; positive predictive value, 5.6%; specificity, 99.997%). Six (67%) of the confirmed‐positive donations were reactive on repeat TMA, of which 4 were IgM‐negative; of these 4, all 3 that could be tested were reactive on minipool TMA. Two confirmed‐positive donors had infections that had been transmitted locally (in Florida), 6 had traveled to ZIKV‐active areas, and 1 had received an experimental ZIKV vaccine. ZIKV RNA levels in red cells ranged from 40 to 800,000 copies per milliliter and were detected up to 154 days after donation, as compared with 80 days of detection in plasma at levels of 12 to 20,000 copies per milliliter. On the basis of industry‐reported costs of testing and the yield of the tests in our study, the cost of identifying 8 mosquito‐borne ZIKV infections through individual‐unit nucleic acid testing was

Intraamniotic Zika virus inoculation of pregnant rhesus macaques produces fetal neurologic disease

5.3 million per ZIKV RNA–positive donation. Conclusions Screening of U.S. blood donations for ZIKV by individual‐donation TMA was costly and had a low yield. Among the 9 confirmed ZIKV‐positive donations, only 4 were IgM‐negative; of these donations, all 3 that were tested were reactive on minipool TMA. (Funded by the American Red Cross and Grifols Diagnostic Solutions.)

Zika, chikungunya and dengue virus incident infections in blood donors in Brazil in 2016: Implications for blood safety and public health surveillance

Zika virus (ZIKV) infection of pregnant women can cause fetal microcephaly and other neurologic defects. We describe the development of a non-human primate model to better understand fetal pathogenesis. To reliably induce fetal infection at defined times, four pregnant rhesus macaques are inoculated intravenously and intraamniotically with ZIKV at gestational day (GD) 41, 50, 64, or 90, corresponding to first and second trimester of gestation. The GD41-inoculated animal, experiencing fetal death 7 days later, has high virus levels in fetal and placental tissues, implicating ZIKV as cause of death. The other three fetuses are carried to near term and euthanized; while none display gross microcephaly, all show ZIKV RNA in many tissues, especially in the brain, which exhibits calcifications and reduced neural precursor cells. Given that this model consistently recapitulates neurologic defects of human congenital Zika syndrome, it is highly relevant to unravel determinants of fetal neuropathogenesis and to explore interventions.Zika virus infection of pregnant women can cause congenital brain defects. Here, Coffey et al. establish a pregnant rhesus macaque model, using intravenous and intraamniotic route of infection, that reliably reproduces fetal neurologic defects of congenital Zika syndrome in humans.