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Thierry Burnouf

Publications and source records attributed to Thierry Burnouf.

8 recordsLinked to original sources

Strengthening antivenom production in Central and South American public laboratories: report of a workshop.

A workshop on antivenom production in Central and South American public laboratories was performed at Instituto Butantan, Sao Paulo, Brazil, from June 12 to June 16, 2006, under the auspices of the program CYTED. The activity was attended by representatives of public laboratories from Costa Rica, Colombia, Perú, Bolivia, Brazil, and Uruguay. Representatives of the World Health Organization (WHO) and the Brazilian Ministry of Health also participated in the workshop. The political, institutional and technological issues related with antivenom manufacture and distribution in these countries were discussed. Current problems on antivenom production and distribution were analyzed, and the need to strengthen collaborative links between countries was stressed, particularly regarding training programs, transfer of technology, and distribution of antivenoms, with the involvement of the Pan American Health Organization and the WHO. Future workshops on other relevant issues, such as quality control and regulatory policies, are being planned, together with collaborative research efforts between the laboratories.

Animals↗

A process for solvent/detergent treatment of plasma for transfusion at blood centers that use a disposable-bag system.

BACKGROUND: Solvent/detergent (S/D) inactivates enveloped viruses in plasma. The current technology requires a plasma fractionation facility and is applied to large plasma pools, which increases the cost and risks of exposure to S/D-resistant pathogens and lowers the content of protein S and alpha2-antiplasmin. Two S/D treatment procedures for single donations or minipools of plasma have been developed with a single-use bag system. STUDY DESIGN AND METHODS: Frozen plasma samples were thawed and treated in disposable bags with either 2 percent tri(n-butyl)phosphate (TnBP) at 37 degrees C or 1 percent TnBP and 1 percent Triton X-45 at 31 degrees C for 4 hours. Plasma samples were extracted three times with 7.5 percent sterile castor oil to remove TnBP and Triton X-45. The TnBP-treated plasma samples were further subjected to a clarifying centrifugation (3800 x g, 30 min). Final plasma samples were dispensed into individual bags and frozen at -30 degrees C. Plasma quality was assessed at each step of the procedures. RESULTS: Both processes yielded greater than 90 percent mean recovery of coagulation factors (clottable fibrinogen, von Willebrand factor, and factors VIII, V, VII, IX, X, and XI), anticoagulants (protein C, protein S), protease inhibitors (antithrombin, alpha2-antiplasmin), total protein, albumin, and immunoglobulins. Global coagulation tests of the treated plasma samples were normal. Final TnBP and Triton X-45 content was less than 10 and 50 ppm, respectively. CONCLUSION: S/D treatment of plasma can be performed in a closed-bag system under conditions that maintain plasma protein quality. The technology is simple, presents advantages over the industrial large-scale S/D plasma process, and could be performed in blood centers.

Blood Banks↗

Assessment of complement activation during membrane-based plasmapheresis procedures.

Previous studies have suggested that plasmapheresis procedures using a separation membrane may activate the complement system and release anaphylatoxins. This study determines the content in C3a/C3a(des Arg) and C5a/C5a(des Arg) in plasma donations obtained by the new Haemonetics Filter Core (FC) procedure and compares it to Baxter Autopheresis C (Auto-C). FC performs sequential blood centrifugation and plasma filtration on a microporous polyethersulfone membrane, while Auto-C removes blood cells by simultaneous gravitation and filtration on a rotating nylon membrane. One group of 34 donors donated on FC and two groups of 30 and 10 donors on Auto-C. Plasma aliquots were taken from the plasma units within 30 min of the end of the collection procedures, frozen at < -30 degrees C and assessed for C3a and C5a at various time points of storage. Mean C3a/C3a(des Arg) in FC plasma (N = 34) was 1,151 (range: 526-2,991), 1,092 (range: 349-3498), and 507 (range: 307-815) ng/ml at time of collection and after 6 and 12 months of storage, respectively. Respective C5a/C5a(des Arg) was 26.6 (range 4.9-74), 18.9 (9.5-42.6), and 30.9 (range: 10.7-62.3) ng/ml. Mean C3a/C3a(des Arg) was higher in Auto-C (P < 0.001): 4,724 ng/ml (N = 10; range: 2,400-7 ,360) and > 4,149 ng/ml (N = 30; 2,408- > 6,430) after 3 and 18 months storage, respectively. Mean C5a/C5a(des Arg) was 32.1 ng/ml (N = 30; range: 10.6-57.2) after 18 months of storage. Complement activation in FC plasmas appears limited compared to Auto-C, suggesting better biocompatibility of this collection device and/or a favourable impact of the sequential cell centrifugation/filtration technology used. Further studies are needed to explain differences in complement activation between apheresis procedures and to assess clinical impacts, if any.

Complement Activation↗

Assessment of the viral safety of antivenoms fractionated from equine plasma.

Antivenoms are preparations of intact or fragmented (F(ab')2 or Fab) immunoglobulin G (IgG) used in human medicine to treat the severe envenomings resulting from the bites and stings of various animals, such as snakes, spiders, scorpions, or marine animals, or from the contact with poisonous plants. They are obtained by fractionating plasma collected from immunized horses or, less frequently, sheep. Manufacturing processes usually include pepsin digestion at acid pH, papain digestion, ammonium sulphate precipitation, caprylic acid precipitation, heat coagulation and/or chromatography. Most production processes do not have deliberately introduced viral inactivation or removal treatments, but antivenoms have never been found to transmit viruses to humans. Nevertheless, the recent examples of zoonotic diseases highlight the need to perform a careful assessment of the viral safety of antivenoms. This paper reviews the characteristics of equine viruses of antivenoms and discusses the potential of some manufacturing steps to avoid risks of viral contamination. Analysis of production parameters indicate that acid pH treatments and caprylic acid precipitations, which have been validated for the manufacture of some human IgG products, appear to provide the best potential for viral inactivation of antivenoms. As many manufacturers of antivenoms located in developing countries lack the resources to conduct formal viral validation studies, it is hoped that this review will help in the scientific understanding of the viral safety factors of antivenoms, in the controlled implementation of the manufacturing steps with expected impact on viral safety, and in the overall reinforcement of good manufacturing practices of these essential therapeutic products.

Animals↗

Protein composition and activation markers in plasma collected by three apheresis procedures.

BACKGROUND: Scientific and technical advances made in transfusion medicine sustain the need for more comprehensive understanding of the impact of collection procedures on the quality of plasma for fractionation and for transfusion. This prospective work evaluated protein composition and markers of activation in plasma donations collected with three different automatic collection procedures (performed on Haemonetics machines), including a new procedure using a high-separation core-molded bowl. STUDY DESIGN AND METHODS: A total of 90 collection procedures have been performed from a population of 37 donors, under comprehensively standardized conditions. Plasma aliquots were taken from the plasma units within 30 minutes of the end of the collection procedures and immediately frozen at -70 degrees C. Content in an extended range of proteins and of markers of activation of the coagulation and fibrinolytic systems has been measured using standard in vitro testing methods. RESULTS: Plasma donations had normal mean total protein, IgG, IgM, and fibrinogen content. The mean levels in coagulation FV, FVII, FVIII, and FXI and in antithrombin were above the standard international requirements. There was no sign of activation of the hemostasis system, as assessed by activated FVII, thrombin antithrombin complex, Prothrombin fragment 1+2, and D-dimers. Activated complement component C3 and C5 were low. CONCLUSION: Data indicates the good and consistent protein composition of plasma obtained by those automatic apheresis procedures. In particular, the new high-separation core procedure yields a high-quality plasma meeting requirements for transfusion and fractionation.

Adult↗

Residual cell content in plasma produced by three centrifugal apheresis procedures.

BACKGROUND: Understanding the impact of collection procedures on the residual amount of blood cells in plasma for transfusion and for fractionation is of current interest. This prospective work evaluated plasma donations collected on an apheresis machine (PCS 2, Haemonetics) with three different automatic centrifugal apheresis procedures, currently largely used in the US (Revision G) and in Europe (Revision F), and included a new procedure that uses a high-separation core (HSC) that is designed with a second separation chamber to further separate cells from plasma. STUDY DESIGN AND METHODS: A total of 90 collection procedures have been performed from a population of 37 donors, under comprehensively standardized conditions. There were 30 well-matched donors in each group. Plasma aliquots were taken from the plasma units within 30 minutes of the end of the collection procedures and immediately assessed for WBCs, RBCs, PLTs, and supernatant Hb. RESULTS: In Revision F and Revision G plasma donations, the mean numbers of WBCs were 83.1 x 10(4) and 311 x 10(4) per L; PLTs, 5.01 x 10(9) and 20 x 10(9) per L; and RBCs, 58 x 10(6) and 43 x 10(6) per L, respectively [corrected]. Significantly lower values were found with the HSC procedure (mean WBC, RBC, and PLT counts, 3.01 x 10(4)/L [p < 0.05], 9 x 10(6)/L [p < 0.001], and 3.5 x 10(9)/L [p < 0.001], respectively). The amount of free Hb was similar in all three procedures. CONCLUSION: Significant differences in numbers of cells in plasma were found depending on the centrifugal procedures used and the design of the separation bowl. The lowest level of cell contamination was found with the new HSC bowl, which without a filtration step, yielded plasma that met the standard for WBC-reduced plasma. Plasma collectors can select the most appropriate method of plasma collection based on donor criteria, use of plasma (transfusion, viral inactivation, or fractionation), and local or international regulations, when in place.

Blood Cell Count↗

AIDS--past and future.

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Acquired Immunodeficiency Syndrome↗