A report of 104 transfusion errors in New York State

In New York State, significant incidents involving the collection, processing, or transfusion of blood must be reported. Incident reports received over a 22-month period involving transfusion of blood to other than the intended recipient or release of blood of an incorrect group were analyzed. Among 1,784,600 transfusions of red cell components; there were 92 cases of erroneous transfusion that met study criteria (1/19,000). There were 54 ABO-incompatible transfusions (1/33,000); three of these (1/600,000) were fatal. Correction for underreporting of ABO-compatible errors resulted in an estimate of 1 per 12,000 as the true risk of transfusion error. National application of New York State data results in an estimate of 800 to 900 projected red cell-associated errors in the United States annually. The majority of reported errors occurred outside of the blood bank (43% resulted solely from failure to identify the patient and/or unit prior to transfusion and 11% resulted from phlebotomist error), while the blood bank was responsible for 25 percent of errors and contributed, with another hospital service, to 17 percent. The risk of transfusion of ABO-incompatible blood remains significant, and additional precautions to minimize the likelihood of such events should be considered.     

Evaluation of a Rapid Serological Test for the Determination of Mycobacterium bovis Infection in Badgers (Meles meles) Found Dead

Between October 2005 and May 2006, a total of 727 badgers found dead in Wales were reported, and 550 were delivered to the Regional Laboratories of the Veterinary Laboratories Agency (VLA). Of the 459 carcasses suitable for examination, 55 were deemed to be infected with Mycobacterium bovis on the basis of culture, spoligotyping, and variable-number tandem repeat typing. Acid-fast bacteria were observed histologically in a further six badgers, but these bacteria were not confirmed as M. bovis by culture. A rapid serological test (BrockTB Stat-Pak) performed on thoracic blood showed a sensitivity of 35% and a specificity of 99%. Presence of M. bovis infection was 45 times more likely to be confirmed postmortem by culture in BrockTB Stat-Pak-reactive animals than in seronegative ones. Using visible carcass lesions as a marker of bovine tuberculosis (bTB) infection had a similar sensitivity (38%) but was significantly less specific (84%) than serology. The overall accuracy of the antibody detection was 93% (346 correct results from 374 tests), whereas the accuracy of regarding visible lesions as a marker for bTB infection was 78% (354 correct from 453 carcasses examined). Culture remains the gold standard method for detecting M. bovis infection in badgers. However, where resources are limited and/or an instant result is preferred, the BrockTB Stat-Pak could be used in field surveillance efforts to identify animals which should be examined further by only submitting test-negative animals to more detailed postmortem examination and culture.Mycobacterium bovis infection is the cause of bovine tuberculosis (bTB) in a wide range of mammal species, including domestic livestock and captive and free-ranging wildlife. Bovine TB remains an important zoonotic disease with significant impacts on the economy in many countries (6, 22, 23). Eurasian badgers (Meles meles) are a wildlife maintenance host of bTB in Great Britain and Ireland (5, 15) and are implicated in the maintenance and onward transmission of M. bovis infection to cattle (10, 19).Surveillance of wildlife vectors of disease for prevalence estimates of infection may be valuable in disease control strategies and for the assessment of risk of transmission to livestock. Diagnosis of bTB in live badgers has been demonstrated using assays of both serological (4, 20) and cell-mediated (8, 9) immunity. While isolation of M. bovis from clinical samples is definitive, it is too insensitive for badgers, as infected animals yield positive samples infrequently and intermittently (3). A rapid serological test (BrockTB Stat-Pak; Chembio Diagnostic Systems, Inc.) has recently been developed for the diagnosis of bTB in multiple wildlife species (20). The test has modest sensitivity (46 to 55%) for antibody detection in live, infected badgers, but it has the advantages of being simple, rapid, inexpensive, and suitable for field application. Its utility as an animal-side test for badgers, however, is limited by the difficulties associated with obtaining a blood sample from a nonanesthetized animal.Where carcasses are recovered and submitted for mycobacterial culture, the sensitivity of diagnosis depends on the effort taken for careful examination and on the number of tissue samples submitted for culture testing and histopathology (7), as well as on the condition of the carcass. In many cases, the cost involved may prove prohibitive. Reliance on the presence of visible lesions as indicative of bTB is fraught with difficulties, as infected animals may present with no visible lesions or lesions may be the result of other infections while having the appearance of bTB (reviewed in reference 13). The purpose of this study was to determine whether the BrockTB Stat-Pak test could detect M. bovis antibody in blood collected from the carcasses of dead badgers as an alternative means of diagnosis and decision making. Animals were obtained as part of a separate government-funded study to determine the prevalence of bTB in badgers found dead in Wales (http://new.wales.gov.uk/depc/publications/environmentandcountryside/animalhealthandwelfare/diseasesurveillancecontrol/bovinetb/2567889/publicationindex/2326585/badgerfounddeadreport?lang=en). Our results reveal that the BrockTB Stat-Pak test used on thoracic blood samples was very specific (99%) but less sensitive (35%) than found previously for live badgers (2, 14). However, bTB was 45 times more likely to be confirmed in BrockTB Stat-Pak-positive animals than in BrockTB Stat-Pak-negative ones, whereas using visible carcass lesions as a marker of infection was less reliable.     

SARS-CoV-2 Omicron variant BA.2 neutralisation in sera of people with Comirnaty or CoronaVac vaccination,infection or breakthrough infection,Hong Kong, 2020 to 2022

BackgroundOmicron subvariant BA.2 circulation is rapidly increasing globally.AimWe evaluated the neutralising antibody response from vaccination or prior SARS-CoV-2 infection against symptomatic infection by BA.2 or other variants.MethodsUsing 50% plaque reduction neutralisation tests (PRNT₅₀), we assessed neutralising antibody titres to BA.2, wild type (WT) SARS-CoV-2 and other variants in Comirnaty or CoronaVac vaccinees, with or without prior WT-SARS-CoV-2 infection. Titres were also measured for non-vaccinees convalescing from a WT-SARS-CoV-2 infection. Neutralising antibodies in BA.2 and BA.1 breakthrough infections and in BA.2 infections affecting non-vaccinees were additionally studied.ResultsIn vaccinees or prior WT-SARS-CoV-2-infected people, BA.2 and BA.1 PRNT₅₀ titres were comparable but significantly (p < 10 ^− 5) lower than WT. In each group of 20 vaccinees with (i) three-doses of Comirnaty, (ii) two CoronaVac followed by one Comirnaty dose, or (iii) one dose of either vaccine after a WT-SARS-CoV-2 infection, ≥ 19 individuals developed detectable (PRNT₅₀ titre ≥ 10) antibodies to BA.2, while only 15 of 20 vaccinated with three doses of CoronaVac did. Comirnaty vaccination elicited higher titres to BA.2 than CoronaVac. In people convalescing from a WT-SARS-CoV-2 infection, a single vaccine dose induced higher BA.2 titres than three Comirnaty (p = 0.02) or CoronaVac (p = 0.00001) doses in infection-naïve individuals. BA.2 infections in previously uninfected and unvaccinated individuals elicited low (PRNT₅₀ titre ≤ 80) responses with little cross-neutralisation of other variants. However, vaccinees with BA.1 or BA.2 breakthrough infections had broad cross-neutralising antibodies to WT viruses, and BA.1, BA.2, Beta and Delta variants.ConclusionsExisting vaccines can be of help against the BA.2 subvariant.     

Immunochemical Characterization of the MPB70/80 and MPB83 Proteins of Mycobacterium bovis

MPB70 and MPB80 (MPB70/80) and MPB83 are closely related antigens which are highly expressed in Mycobacterium bovis. MPB70/80 are soluble secreted antigens, while MPB83 is an exported lipoprotein associated with the bacterial surface. In the present study, these antigens had different mobilities in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing and nonreducing conditions. These differences may be explained by the fact that MPB70 and MPB83 both have two internal cysteine residues which would create ring structures by disulfide bonding. We analyzed the structures of MPB70/80 and MPB83 by using monoclonal antibodies (MAbs) raised against bovine purified protein derivative or whole M. bovis cells. MAb 1-5C reacted specifically with MPB70 and MPB80, and MAb MBS43 reacted specifically with MPB83, while the other antibodies, including several previously described MAbs, bound all three antigens. MAbs and polyclonal antibodies reacted strongly with reduced protein and less well with nonreduced protein, indicating involvement of linear epitopes. Epitopes of MAbs Bov-1, 2-6B, 1-5C, and 1-1D were mapped by using synthetic peptides of MPB70. Sequence comparison showed the peptide with the 1-5C-reactive epitope to have three residues different from those in the homologous region of MPB83. Exchanges of A for S in position 112 or Q for E in position 116 abolished the reactivity of MAb 1-5C. Polyclonal rabbit antibodies to native purified MPB70 reacted strongly with peptides 6, 7, and 8 of the N-terminal half of mature MPB70. Cattle sera of experimentally M. bovis-infected animals recognized a broader spectrum of peptides. These findings indicate that there is diagnostic potential for these proteins and that there is also a possible role for antibodies in elucidation of the host-mycobacterium relationship involving a surface-bound and exposed lipoprotein, MPB83, and its highly homologous soluble secreted MPB70/80 counterparts.     

Use of Mycobacterium tuberculosis Complex-Specific Antigen Cocktails for a Skin Test Specific for Tuberculosis

The tuberculin skin test currently used to diagnose infection with Mycobacterium tuberculosis has poor diagnostic value, especially in geographic areas where the prevalence of tuberculosis is low or where the environmental burden of saprophytic, nontuberculous mycobacteria is high. Inaccuracy of the tuberculin skin test often reflects a low diagnostic specificity due to the presence in tuberculin of antigens shared by many mycobacterial species. Thus, a skin test specific for tuberculosis requires the development of new tuberculins consisting of antigens specific to M. tuberculosis. We have formulated cocktails of two to eight antigens of M. tuberculosis purified from recombinant Escherichia coli. Multiantigen cocktails were evaluated by skin testing guinea pigs sensitized with M. bovis BCG. Reactivity of multiantigen cocktails was greater than that of any single antigen. Cocktail activity increased with the number of antigens in the cocktail even when the same amount of total protein was used for cocktails and for each single antigen. A cocktail of four purified antigens specific for the M. tuberculosis complex elicited skin test responses only in BCG-immunized guinea pigs, not in control animals immunized with M. avium. These findings open the way to designing a multiantigen formulation for a skin test specific for tuberculosis.     

Heterogeneous Antibody Responses in Tuberculosis

Antibody responses during tuberculosis were analyzed by an enzyme-linked immunosorbent assay with a panel of 10 protein antigens of Mycobacterium tuberculosis. It was shown that serum immunoglobulin G antibodies were produced against a variety of M. tuberculosis antigens and that the vast majority of sera from tuberculosis patients contained antibodies against one or more M. tuberculosis antigens. The number and the species of serologically reactive antigens varied greatly from individual to individual. In a given serum, the level of specific antibodies also varied with the antigen irrespective of the total number of antigens recognized by that particular serum. These findings indicate that person-to-person heterogeneity of antigen recognition, rather than recognition of particular antigens, is a key attribute of the antibody response in tuberculosis.     

Tonsils of the Soft Palate Do Not Mediate the Response of Pigs to Oral Vaccination with Heat-Inactivated Mycobacterium bovis

Mycobacterium bovis causes animal tuberculosis (TB) in cattle, humans, and other mammalian species, including pigs. The goal of this study was to experimentally assess the responses of pigs with and without a history of tonsillectomy to oral vaccination with heat-inactivated M. bovis and challenge with a virulent M. bovis field strain, to compare pig and wild boar responses using the same vaccination model as previously used in the Eurasian wild boar (Sus scrofa), to evaluate the use of several enzyme-linked immunosorbent assays (ELISAs) and lateral flow tests for in vivo TB diagnosis in pigs, and to verify if these tests are influenced by oral vaccination with inactivated M. bovis. At necropsy, the lesion and culture scores were 20% to 43% higher in the controls than those in the vaccinated pigs. Massive M. bovis growth from thoracic tissue samples was observed in 4 out of 9 controls but in none of the 10 vaccinated pigs. No effect of the presence or absence of tonsils was observed on these scores, suggesting that tonsils are not involved in the protective response to this vaccine in pigs. The serum antibody levels increased significantly only after challenge. At necropsy, the estimated sensitivities of the ELISAs and dual path platform (DPP) assays ranged from 89% to 94%. In the oral mucosa, no differences in gene expression were observed in the control group between the pigs with and without tonsils. In the vaccinated group, the mRNA levels for chemokine (C-C motif) receptor 7 (CCR7), interferon beta (IFN-β), and methylmalonyl coenzyme A mutase (MUT) were higher in pigs with tonsils. Complement component 3 mRNA levels in peripheral blood mononuclear cells (PBMC) increased with vaccination and decreased after M. bovis challenge. This information is relevant for pig production in regions that are endemic for M. bovis and for TB vaccine research.