Hany Kamel

Tregs control the development of symptomatic West Nile virus infection in humans and mice

West Nile virus (WNV) causes asymptomatic infection in most humans, but for undefined reasons, approximately 20% of immunocompetent individuals develop West Nile fever, a potentially debilitating febrile illness, and approximately 1% develop neuroinvasive disease syndromes. Notably, since its emergence in 1999, WNV has become the leading cause of epidemic viral encephalitis in North America. We hypothesized that CD4+ Tregs might be differentially regulated in subjects with symptomatic compared with those with asymptomatic WNV infection. Here, we show that in 32 blood donors with acute WNV infection, Tregs expanded significantly in the 3 months after index (RNA+) donations in all subjects. Symptomatic donors exhibited lower Treg frequencies from 2 weeks through 1 year after index donation yet did not show differences in systemic T cell or generalized inflammatory responses. In parallel prospective experimental studies, symptomatic WNV-infected mice also developed lower Treg frequencies compared with asymptomatic mice at 2 weeks after infection. Moreover, Treg-deficient mice developed lethal WNV infection at a higher rate than controls. Together, these results suggest that higher levels of peripheral Tregs after infection protect against severe WNV disease in immunocompetent animals and humans.

Virus and Antibody Dynamics in Acute West Nile Virus Infection

BACKGROUND The dynamics of the early stages of West Nile virus (WNV) infection can be assessed by follow-up studies of viremic blood donors. METHODS A total of 245 donors with WNV viremia were followed up weekly for 4 weeks and then monthly for up to 6 additional months or until seroconversion. Plasma samples were tested for WNV RNA by transcription-mediated amplification (TMA) and for WNV-specific IgM and IgG antibodies. RNA persistence was investigated by 6 replicate TMA tests; samples that were viremic for >40 days were tested for WNV-neutralizing activity. Follow up of 35 additional viremic donors for up to 404 days was conducted to evaluate persistence of WNV-specific antibody. RESULTS The median time from RNA detection to IgM seroconversion was 3.9 days; to IgG seroconversion, 7.7 days; to RNA negativity by single-replicate TMA, 13.2 days; and to RNA negativity by 6-replicate TMA, 6.1 additional days after results of single-replicate TMA are negative. For 4 donors in whom RNA persisted for >40 days after the index donation, all samples obtained after this threshold were also positive for WNV IgG and neutralizing activity. The mean times to IgM and IgA negativity were 156 and 220 days, respectively. CONCLUSIONS IgM and IgG develop rapidly after viremia and before RNA levels become undetectable, which occurred a mean of 13.2 days after the index donation among donors in this study. WNV RNA detection by replicate TMA rarely persists for >40 days after the index donation and is accompanied by WNV-specific neutralizing antibody, consistent with an absence of WNV transmission via transfusion of seropositive blood components.

Faint and prefaint reactions in whole-blood donors: an analysis of predonation measurements and their predictive value.

BACKGROUND: A small proportion of blood donors have adverse reactions. The purpose of this study was to determine predictors of faint and significant hypotensive reactions that could serve as targets for interventions to reduce reactions, thus improving the blood donation experience for those at higher risk of reactions and reducing the risk of serious adverse events.

The United States Trypanosoma cruzi Infection Study: evidence for vector-borne transmission of the parasite that causes Chagas disease among United States blood donors.

BACKGROUND: Screening US blood donors for Trypanosoma cruzi infection is identifying autochthonous, chronic infections. Two donors in Mississippi were identified through screening and investigated as probable domestically acquired vector‐borne infections, and the US T. cruzi Infection Study was conducted to evaluate the burden of and describe putative risk factors for vector‐borne infection in the United States.

West Nile virus infection transmitted by blood transfusion

BACKGROUND: A patient with transfusion‐transmitted West Nile virus (WNV) infection confirmed by viral culture of a blood component is described. A 24‐year‐old female with severe postpartum hemorrhage developed fever, chills, headache, and generalized malaise after transfusion of 18 units of blood components; a serum sample and the cerebrospinal fluid tested positive for the presence of WNV IgM antibodies. An investigation was initiated to determine a possible association between transfusion and WNV infection.

Delayed adverse reactions to blood donation.

BACKGROUND: Blood donation is safe, but a small proportion of donors have delayed and/or off‐site reactions that have the potential to lead to serious injury. This retrospective study sought to identify risk factors for delayed reactions (DRs).

Genetic Diversity of Recently Acquired and Prevalent HIV, Hepatitis B Virus, and Hepatitis C Virus Infections in US Blood Donors

BACKGROUND Genetic variations of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) can affect diagnostic assays and therapeutic interventions. Recent changes in prevalence of subtypes/genotypes and drug/immune-escape variants were characterized by comparing recently infected vs more remotely infected blood donors. METHODS Infected donors were identified among approximately 34 million US blood donations, 2006-2009; incident infections were defined as having no or low antiviral antibody titers. Viral genomes were partially sequenced. RESULTS Of 321 HIV strains (50% incident), 2.5% were non-B HIV subtypes. Protease and reverse transcriptase (RT) inhibitor resistance mutations were found in 2% and 11% of infected donors, respectively. Subtypes in 278 HCV strains (31% incident) yielded 1a>1b>3a>2b>2a>4a>6d, 6e: higher frequencies of 3a in incident cases vs higher frequencies of 1b in prevalent cases were found (P = .04). Twenty subgenotypes among 193 HBV strains (26% incident) yielded higher frequencies of A2 in incident cases and higher frequencies of A1, B2, and B4 in prevalent cases (P = .007). No HBV drug resistance mutations were detected. Six percent of incident vs 26% of prevalent HBV contained antibody neutralization escape mutations (P = .01). CONCLUSIONS Viral genetic variant distribution in blood donors was similar to that seen in high-risk US populations. Blood-borne viruses detected through large-scale routine screening of blood donors can complement molecular surveillance studies of highly exposed populations.

BLOOD DONORS AND BLOOD COLLECTION: Delayed adverse reactions to blood donation

BACKGROUND: Blood donation is safe, but a small proportion of donors have delayed and/or off‐site reactions that have the potential to lead to serious injury. This retrospective study sought to identify risk factors for delayed reactions (DRs).

Physiologic strategies to prevent fainting responses during or after whole blood donation.

Vasovagal syncope (VVS) is a consistent, but infrequent (0.1%‐0.3%) complication of volunteer, whole blood donation. Given the large number of blood donations, a significant number of donors is involved. Syncope occasionally leads to injury. Recent rigorous data collection and analysis have led to the association of a small number of donor and donation factors with the risk of syncope. An analysis of the time course of syncope reactions among approximately 500,000 whole blood donors suggests that there are three distinct periods of risk for vasovagal reactions before, during, and after phlebotomy. This review examines the physiologic mechanisms that contribute to these periods of increased risk including the direct effects of removal of approximately 500 mL of whole blood, the psychological stress of instrumentation and giving blood (i.e., fear of needles, pain, and the sight of blood), and the orthostatic effects superimposed on a hypovolemic state after the donation. Specifically, we describe interventions that have been useful in controlling VVS in patients with fainting syndromes and we examine the potential of these interventions in the blood donation context, based on the physiologic principles involved. Finally, we propose an intervention (dietary replacement of salt lost with blood donation) that has not been applied in transfusion medicine previously but which has the potential to reduce risk.

West Nile virus nucleic acid persistence in whole blood months after clearance in plasma: implication for transfusion and transplantation safety.

Previous reports of West Nile virus (WNV) RNA persistence in blood compartments have raised concerns around the remaining risk of WNV transfusion transmission. This study characterized the dynamics of WNV viremia in blood compartments in a longitudinal cohort of 54 WNV‐infected blood donors.