Characterization of antibodies in human immunoglobulin products from different regions worldwide.

AIM: The antibody levels against a broad spectrum of pathogens were assessed in commercial intravenous immunoglobulin (IVIG) manufactured from pooled plasma obtained from different global regions. METHODS: Twenty-four IVIG commercial lots from eight manufacturers corresponding to 12 brands were analyzed. The plasma was collected in 10 countries/regions. Depending on each pathogen, antibody levels were measured using specific commercial IgG-specific enzyme immunoassay kits or by cell culture neutralization test and guinea pig skin neutralization test. A principal component analysis was performed. RESULTS: For polio and diphtheria (reference markers of the US authorities), all IVIGs had relevant titers in accordance with reference levels. IVIGs from Canada, Australia, and the USA were positive for titers against globally distributed pathogens or those under vaccination programs in the developed world (parainfluenza, Epstein-Barr, varicella-zoster, influenza B, parvovirus B19, and measles viruses). IVIG from Taiwan and Hong Kong showed low antibody titers for these pathogens but high titers for Pseudomonas aeruginosa. IVIG from India had high titers for pathogens frequently found in developing countries (West Nile, dengue, chikungunya, and hepatitis E viruses and Streptococcus pneumoniae). IVIGs from Argentina, Spain, Israel, and Czechia showed intermediate antibody concentrations. CONCLUSION: The antibody profile in IVIG was greatly influenced by regional characteristics including climate, vaccination programs, and the prevalence of pathogens in the different countries and regions.

Plasma is a strategic resource.

Plasma-derived medicinal products (PDMPs) such as immunoglobulins and clotting factors are listed by the World Health Organization as essential medicines. These and other PDMPs are crucial for the prophylaxis and treatment of patients with bleeding disorders, immune deficiencies, autoimmune and inflammatory diseases, and a variety of congenital deficiency disorders. While changes in clinical practice in developed countries have reduced the need for red blood cell transfusions thereby significantly reducing the collection volumes of whole blood and recovered plasma suitable for fractionation, the need for PDMPs worldwide continues to increase. The majority of plasma supplies for the manufacture of PDMPs is met by the US commercial plasma industry. However, geographic imbalance in the collection of plasma raises concerns that local disruptions of plasma supplies could result in regional and global shortages of essential PDMPs. Plasma, which fits the definition of a strategic resource, that is, "an economically important raw material which is subject to a higher risk of supply interruption," should be considered a strategic resource comparable to energy and drinking water. Plasma collections should be increased outside the United States, including in low- and middle-income countries. The need for capacity building in these countries is an essential part to strengthen quality plasma collection. This will require changes in national and regional policies. We advocate the need for the restoration of an equitable balance of the international plasma supply to reduce the risk of supply shortages worldwide. Strategic independence of plasma should be endorsed on a global level.

A possible new paradigm? A survey-based assessment of the use of thawed group A plasma for trauma resuscitation in the United States.

BACKGROUND: Although evidence supporting this practice is limited, some centers use thawed group A plasma for the initial resuscitation of trauma patients. STUDY DESIGN AND METHODS: To better understand the current use of plasma in trauma resuscitation, a survey was developed, validated, and distributed via e-mail to 121 American trauma centers. RESULTS: A total of 61 responses were received. Most were from Level 1 trauma centers (56/61, 92%) in urban settings (47/61, 77%). Virtually all centers reported maintaining A thawed plasma inventory (59/61, 97%). Among the 56 Level 1 trauma center respondents, most keep thawed A immediately available (49/56, 88%) and many use group A plasma for trauma recipients of unknown ABO group (34/49, 69%). Half of the surveyed centers implemented this practice within the past year. The majority do not limit the amount of A plasma that can be administered to a patients of unknown ABO group (21/34, 62%), and most do not titer for anti-B (27/34, 79%). CONCLUSION: The majority of Level 1 trauma centers maintain thawed plasma inventories and use group A plasma for trauma recipients of unknown ABO group. Most centers do not limit the amount of group A plasma used in this situation or titer the anti-B.

Assessment of the neutrophilic antibody-dependent respiratory burst (ADRB) response to Plasmodium falciparum.

Semi-immunity against Pf malaria is based on a combination of cellular and humoral immune responses. PMNs and IgGs are considered important components of this process, but the underlying mechanisms are unclear. We investigated the neutrophilic ADRB by analyzing the production of ROS in response to Pf antigen-specific IgGs bound to solid-phase immobilized antigens (sADRB) or whole merozoites (mADRB). We found that the PMN stimulations in each assay were based on different underlying mechanisms, demonstrating the importance of the assay set-up for the evaluation of antibody-triggered PMN responses. In the sADRB assay, ROS were produced externally, and by specific blocking of CD32(a)/FcγRII(a), the immediate neutrophilic response was abolished, whereas the removal of CD16(b)/FcγRIII(b) had no substantial effect. The key role of CD32(a) was confirmed using CD16(b)-deficient PMNs, in which similar changes of neutrophilic ADRB profiles were recorded after treatment. In the mADRB assay, ROS were produced almost exclusively within the cell, suggesting that the underlying mechanism was phagocytosis. This was confirmed using an additional phagocytosis assay, in which PMNs specifically ingested merozoites opsonized with Ghanaian plasma IgGs, seven times more often than merozoites opsonized with European plasma IgGs (P<0.001). Our data show that assay set-ups used to evaluate the responses of PMNs and perhaps other effector cells must be chosen carefully to evaluate the appropriate cellular responses. Our robust, stable, and well-characterized methods could therefore be useful in malaria vaccine studies to analyze the antimalarial effector function of antibodies.

Serologic testing for syphilis in the United States: a cost-effectiveness analysis of two screening algorithms.

BACKGROUND: The introduction of automated treponemal enzyme immunoassays and chemiluminescence assays (EIA/CA) tests has led some laboratories in the United States to use new syphilis screening algorithms that start with a treponemal test. We compared the economic and health outcomes of this new algorithm with the standard algorithm from the perspective of the United States health system. METHODS: We used a cohort decision analysis to estimate the expected costs and effects (including follow-ups and overtreatment) of the 2 algorithms from a health-care system perspective. In the standard algorithm, rapid plasma reagin (RPR) is followed (if reactive) by EIA/CA (Nontreponemal-First). In the new algorithm, EIA/CA is followed (if reactive) by RPR. If the RPR is negative, Treponema pallidum passive particle agglutination assay (TP-PA) test is used (Treponemal-First). RESULTS: For a cohort of 200,000 individuals (1000 current infections and 10,000 previous infections), the net costs were $1.6 m (Treponemal-First) and $1.4 m (Nontreponemal-First). The Treponemal-First option treated 118 more cases (986 vs. 868) but resulted in a substantially higher number of follow-ups (11,450 vs. 3756) and overtreatment (964 vs. 38). Treating the additional 118 cases might prevent 1 case of tertiary syphilis. The estimated cost-effectiveness ratios were $1671 (Treponemal-First) and $1621 (Nontreponemal-First) per case treated. The overtreatment was a function of the specificity of the EIA/CA and the lack of independence of EIA/CA and TP-PA. CONCLUSION: The Treponemal-First option costs slightly more and results in more unnecessary treatment.

The tale of two serologic tests to screen for syphilis--treponemal and nontreponemal: does the order matter?

BACKGROUND: Standard syphilis screening involves an initial screening with a nontreponemal test and confirmation of positives with a treponemal test. However, some laboratories have reversed the order. There is no detailed quantitative and qualitative evaluation for the order of testing. In this study, we analyzed the health and economic outcomes of the order of testing for the 2 serologic tests used in syphilis screening under pure screening settings. METHODS: We used a cohort decision analysis to examine the health and economic outcomes of the screening algorithms for low and high prevalence settings. The 2-step algorithms were nontreponemal followed by treponemal (Nontrep-First) and treponemal followed by nontreponemal (Trep-First). We included the 1-step algorithms (treponemal only [Trep-Only] and an on-site nontreponemal only [Nontrep-Only]) for comparison. We estimated overtreatment rates and the number of confirmatory tests required for each algorithm. RESULTS: For a cohort of 10,000 individuals, our results indicated that the overtreatment rates were substantially higher (more than 3 times) for the 1-step algorithms, although they treated a higher number of cases (over 15%). The 2-step algorithms detected and treated the same number of individuals. Among the 2-step algorithms, the Nontrep-First was more cost-effective in the low prevalence setting ($1400 vs. $1500 per adverse outcome prevented) and more cost-saving ($102,000 vs. $84,000) in the high prevalence setting. CONCLUSIONS: The difference in cost was largely due to the substantially higher number of confirmatory tests required for the Trep-First algorithm, although the number of cases detected and treated was the same.

Indications for use and cost-effectiveness of pathogen-reduced ABO-universal plasma.

PURPOSE OF REVIEW: Donor selection and viral screening methods combined with pathogen reduction have increased the safety of pooled plasma to a level which makes reintroduction of ABO-universal plasma an important option. RECENT FINDINGS: Solvent detergent-treated pooled plasma has proved to be well suited for the production of pathogen-reduced ABO-universal plasma. One such product, Bioplasma FDP, was licensed in South Africa in 1994 and has since 1996 been in successful clinical use. A clinical study with this product and two studies with the European product, Uniplas, have confirmed the efficacy and safety of pathogen-reduced ABO-universal plasma. SUMMARY: Pooling of plasma enables the production of ABO-universal plasma. Pathogen reduction with solvent detergent eliminates lipid-enveloped viruses, whereas neutralizing antibodies in the plasma pool and nucleic acid amplification testing ensures the safety for recognized nonlipid-enveloped viruses. Pooling also eliminates transfusion-associated acute lung injury (the leading cause of plasma transfusion-related death), reduces immunologic/allergic adverse events by 60-80% and standardizes plasma protein content. Thus, in addition to ABO compatibility, pathogen-reduced ABO-universal plasma has important supplementary benefits that improve the product's cost-effectiveness.

Significant numbers of apheresis-derived group O platelet units have "high-titer" anti-A/A,B: implications for transfusion policy.

Transfusion of group O single-donor apheresis PLTs (SDP) to group A recipients has resulted in intravascular hemolysis and mortality. Owing to low availability of type-specific SDPs, transfusion services sometimes issue ABO-mismatched PLTs. After observing two cases of acute hemolysis following infusion of O SDPs to group A patients, where both recipient eluates revealed anti-A specificity, a prospective study to determine the prevalence of "high-titer" anti-A/A,B in group O SDPs was commenced. One hundred group O SDP samples were tested. Titers of at least 64 and/or 256 from either buffered (generally reflective of IgM antibodies) or anti-IgG gel cards, respectively, were considered critically high. Twenty-eight and 39 percent of samples revealed critically high anti-A/A,B IgM and IgG titers, respectively. IgM titers were at 1:64 (18%), 128 (6%), and 256 (4%), whereas IgG titers were at 1:256 (28%), 512 (7%), 1024 (2%), and 2048 (2%). The prevalence of critical anti-A/A,B titers in group O SDPs is relatively high. Thus, the risk of minor side ABO mismatch and potential intravascular hemolysis during group O SDP transfusion to group A recipients may be significant. Based on these data, a policy was instituted to test anti-A/A,B titers in O SDPs prior to "out-of-group" transfusion.

[The comprehensive assessment of the degree of severity of their condition in patients with mechanical jaundice]. / Kompleksnaia otsenka stepeni tiazhesti sostoianiia bol'nykh s mekhanicheskoi zheltukhoi.

The authors examined 42 patients with obstructive jaundice of various severity. Comparison of the findings of radiohepatography with intoxication values according to the medium-weight molecule test and the biochemical parameters revealed statistically significant differences of some quantitative indices depending of the severity of jaundice. The results of the study made it possible to recommend the use of the values of blood clearance, time of maximum accumulation of a radiopharmacological agent in the liver, hepatic and blood retention index, and the medium-weight molecule test for objective quantitative appraisal of the severity of obstructive jaundice. Study of the time course of changes of the above parameters showed that normalization of hepatic function in resolving jaundice begins only from the second week after decompression of the biliary tract, which must be borne in mind in choosing the optimal time for the operation.