Hepatitis C virus (HCV) continues to spread worldwide with an annual increase of 1.75 million new infections. The number of HCV cases in the U.S. is now greater than the number of HIV cases and is increasing in young adults because of the opioid epidemic sweeping the country. HCV-related liver disease is the leading indication of liver transplantation. An effective vaccine is of paramount importance to control and prevent HCV infection. While this vaccine will need to induce both cellular and humoral immunity, this review is focused on the required antibody responses. For highly variable viruses, such as HCV, isolation and characterization of monoclonal antibodies mediating broad virus neutralization are an important guide for vaccine design. The viral envelope glycoproteins, E1 and E2, are the main targets of these antibodies. Epitopes on the E2 protein have been studied more extensively than epitopes on E1, due to higher antibody targeting that reflects these epitopes having higher degrees of immunogenicity. E2 epitopes are overall organized in discrete clusters of overlapping epitopes that ranged from high conservation to high variability. Other epitopes on E1 and E1E2 also are targets of neutralizing antibodies. Taken together, these regions are important for vaccine design. Another element in vaccine design is based on information on how the virus escapes from broadly neutralizing antibodies. Escape mutations can occur within the epitopes that are involved in antibody binding and in regions that are not involved in their epitopes, but nonetheless reduce the efficiency of neutralizing antibodies. An understanding on the specificities of a protective B cell response, the molecular locations of these epitopes on E1, E2, and E1E2, and the mechanisms, which enable the virus to negatively modulate neutralizing antibody responses to these regions will provide the necessary guidance for vaccine design.
A patient's serum agglutinated most commercial antibody screening and panel identification red blood cells; however, it did not agglutinate either the cells of ABO compatible donors or washed, saline suspended commercial cells. When suspended in a solution containing 0.1 mg/ml neomycin, all cells, including the patient's, were agglutinated by the patient's serum. Inhibition did not occur by preincubation of either the patient's serum or the test cells with 10 mg/ml neomycin. Serum preincubation with butirosin, kanamycin, or neamine inhibited immediate agglutination in the presence of neomycin. The reactive group is, therefore, included in the neamine fragment. Ultracentrifugation segregated the antibody in the 7S fraction. Following separation by column chromatography, only fractions containing IgA demonstrated antineomycin activity.
Background and ObjectivesHepatitis E virus (HEV) is an underrecognized and emerging infectious disease that may threaten the safety of donor blood supply in many parts of the world. We sought to elucidate whether our local community blood supply is at increased susceptibility for transmission of transfusion‐associated HEV infections.Materials and MethodsWe screened 10,002 randomly selected donations over an 8‐month period between 2017 and 2018 at the Stanford Blood Center for markers of HEV infection using commercial IgM/IgG serological tests and reverse transcriptase quantitative polymerase chain reaction assays (RT‐qPCR). Donor demographic information, including gender, age, self‐identified ethnicity, location of residence and recent travel, were obtained from the donor database and used to generate multivariate binary logistic regressions for risk factors of IgG seropositivity.ResultsA total of 10,002 blood donations from 7507 unique donors were screened, and there was no detectable HEV RNA by RT‐qPCR. The overall seropositivity rate was 12.1% for IgG and 0.56% for IgM. Multivariate analysis of unique donors revealed a significantly higher risk of IgG seropositivity with increasing age, White/Asian ethnicities and residence in certain local counties.ConclusionAlthough HEV IgG seroprevalence in the San Francisco Bay Area is consistent with ongoing infection, the screening of a large donor population did not identify any viraemic blood donors. While HEV is an underrecognized and emerging infection in other regions, there is no evidence to support routine blood screening for HEV in our local blood supply currently; however, periodic monitoring may still be required to assess the ongoing risk.
Social isolation, logistical challenges, and limited access to mental health providers who accept Medicare contribute to older adults having a higher risk for untreated depression. Primary care providers (PCPs) are strained due to time demands and lack of training in behavioral activation and similar therapies. This study was designed to reduce depression in older adult primary care patients without burdening their PCPs. We evaluated whether outpatients age 65+ with mild to moderate self-reported depressive symptoms (measured by PHQ-8) benefited from a brief evidence-informed program, the Positive Experience Project(PEP). This is derived from the tenets and practices of both behavioral activation and the “tiny habits” program. The former emphasizes the value of increasing engagement in everyday positive activities to lift mood; the latter provides a method to enhance success by encouraging patients to link these activities with existing habitual behaviors, and to celebrate completion. A script was written for each of four 30-minute sessions conducted in small groups using a telehealth platform. An analysis of patients of the first author yielded 50 eligible patients. 8 were invited to participate and 7 did. The group’s mean PHQ-8 score pre-intervention was 10.1; post-intervention (4 weeks later), the average was 6.1 (P=.039). The use of “scripts” that guide the PCP through the visit enhances adoption. And PCPs can bill for these 30-minute sessions, making it feasible to help patients receive treatment for their depression. These promising results are currently being replicated by additional PCPs and their data will be included in the poster presentation.
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