Although rotavirus infections are generally considered to be confined to the intestine, recent reports suggest that extraintestinal disease occurs. We studied whether rotavirus infection was associated with antigenemia during a major outbreak of gastroenteritis in the Kingston metropolitan area, during July-August 2003. Rotavirus antigen was identified in 30 of 70 acute-phase serum samples (including from 2 deceased individuals) but in only 1 of 53 control samples. Serum antigen levels were inversely associated with time since symptom onset and were directly associated with antigen levels in stool (P = .02). Serum antigen levels were significantly elevated during primary infections (acute-phase serum immunoglobulin G [IgG] titers, <25), compared with those in subsequent infections (acute-phase serum IgG titers, > or = 25) (P = .02). Antigenemia was common in this outbreak and might provide a mechanism to help explain rare but well-documented reports of findings of extraintestinal rotavirus. In situations in which stool samples are not readily available (i.e., patients with severe dehydration or those recently recovered or deceased), serum testing by enzyme immunoassay offers a new and practical diagnostic tool.

We evaluated the protective role of passively transferred circulating antibodies in protecting non-human primates against experimental rotavirus infection. Pooled sera with rotavirus-specific IgG titers that were either high (1:10,000), intermediate (1:300), or negative (<1:25) were infused i.v. into naïve pigtailed macaques (ages 3-6 months). Rotavirus-specific IgG could be detected in the sera at 18 h in all animals infused with antibody-containing serum, and fecal IgG titers could be detected only in animals given high-titer pooled sera. When orally challenged with 10 6 fluorescent-forming units of a simian rotavirus strain, YK-1, at 18 h after serum transfer, control animals shed virus starting 1-3 days after challenge and continued to shed virus at high titers for 6 -8 days, whereas passively immunized macaques did not shed virus or had delayed shedding at low titers for only a limited time. The observation that passively transferred antibodies can suppress or delay viral infection in rotavirus-challenged pigtailed macaques has important implications for the design and testing of parenteral candidate rotavirus vaccines.non-human primate ͉ passive immunization

BackgroundThe Alere point-of-care (POC) Pima™ CD4 analyzer allows for decentralized testing and expansion to testing antiretroviral therapy (ART) eligibility. A consortium conducted a pooled multi-data technical performance analysis of the Pima CD4.MethodsPrimary data (11,803 paired observations) comprised 22 independent studies between 2009–2012 from the Caribbean, Asia, Sub-Saharan Africa, USA and Europe, using 6 laboratory-based reference technologies. Data were analyzed as categorical (including binary) and numerical (absolute) observations using a bivariate and/or univariate random effects model when appropriate.ResultsAt a median reference CD4 of 383 cells/μl the mean Pima CD4 bias is -23 cells/μl (average bias across all CD4 ranges is 10 % for venous and 15 % for capillary testing). Sensitivity of the Pima CD4 is 93 % (95 % confidence interval [CI] 91.4 % - 94.9 %) at 350 cells/μl and 96 % (CI 95.2 % - 96.9 %) at 500 cells/μl, with no significant difference between venous and capillary testing. Sensitivity reduced to 86 % (CI 82 % - 89 %) at 100 cells/μl (for Cryptococcal antigen (CrAg) screening), with a significant difference between venous (88 %, CI: 85 % - 91 %) and capillary (79 %, CI: 73 % - 84 %) testing. Total CD4 misclassification is 2.3 % cases at 100 cells/μl, 11.0 % at 350 cells/μl and 9.5 % at 500 cells/μl, due to higher false positive rates which resulted in more patients identified for treatment. This increased by 1.2 %, 2.8 % and 1.8 %, respectively, for capillary testing. There was no difference in Pima CD4 misclassification between the meta-analysis data and a population subset of HIV+ ART naïve individuals, nor in misclassification among operator cadres. The Pima CD4 was most similar to Beckman Coulter PanLeucogated CD4, Becton Dickinson FACSCalibur and FACSCount, and less similar to Partec CyFlow reference technologies.ConclusionsThe Pima CD4 may be recommended using venous-derived specimens for screening (100 cells/μl) for reflex CrAg screening and for HIV ART eligibility at 350 cells/μl and 500 cells/μl thresholds using both capillary and venous derived specimens. These meta-analysis findings add to the knowledge of acceptance criteria of the Pima CD4 and future POC tests, but implementation and impact will require full costing analysis.

During infection of a new host, the first surfaces encountered by herpes simplex viruses are the apical membranes of epithelial cells of mucosal surfaces. These cells are highly polarized, and the protein composition of their apical and basolateral membranes are very different, so that different viral entry pathways have evolved for each surface. To determine whether the viral glycoprotein G (gG) is specifically required for efficient infection of a particular surface of polarized cells, apical and basal surfaces were infected with wild-type virus or a gG deletion mutant. After infection of polarized cells in culture, the gG ؊ virus was deficient in infection of apical surfaces but was able to infect cells through basal membranes, replicate, and spread into surrounding cells. The gG-dependent step in apical infection was a stage beyond attachment. After in vivo infection of apical surfaces of epithelial cells of nonscarified mouse corneas, infection by glycoprotein C ؊ or gG ؊ virus was considerably reduced as compared with that observed after infection with wild-type virus. In contrast, when corneas were scarified, allowing virus access to other cell surfaces, the gG and glycoprotein C deletion mutants infected eyes as efficiently as wild-type viruses. A secondary mutation allowing infection of apical surfaces by gG ؊ virus arose readily during passage of the virus in nonpolarized cells, indicating that either the gG-dependent step of apical infection can be bypassed or that another viral protein can acquire the same function.