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Comment
. 2016 Dec 8;375(23):2307-2309.
doi: 10.1056/NEJMc1609116. Epub 2016 Nov 14.

Efficacy of Convalescent Plasma in Relation to Dose of Ebola Virus Antibodies

Collaborators, Affiliations
Comment

Efficacy of Convalescent Plasma in Relation to Dose of Ebola Virus Antibodies

Johan van Griensven et al. N Engl J Med. .
No abstract available

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Figures

Figure 1
Figure 1. Titers of Total IgG and Neutralizing Antibodies against the Ebola Virus (EBOV) in Plasma from Convalescent Donors, Distribution of Total-Antibody Doses Given to Patients, Odds Ratios for Death between Days 3 and 16, and Changes in Cycle-Threshold Value after Transfusion.
Panel A shows the distribution of titers of total anti-EBOV IgG and neutralizing antibodies against EBOV in 85 donations from 58 convalescent donors whose plasma was used in the trial. ND denotes not detected. Panel B shows the distribution of the total dose of antibodies administered to patients with EBOV disease. To calculate the total dose that a patient received, the volume of the plasma unit was multiplied by the corresponding optical-density value from the enzyme-linked immunosorbent assay (for total anti-EBOV IgG) or antibody titer (for neutralizing antibodies); the sum of this measure for all plasma units that a patient received represented the estimated total-antibody dose. The total dose of neutralizing antibodies has been divided by a factor of 10. Infused plasma in which no antibodies were detected were allocated a zero dose in the estimation of the total dose. The dashed lines show the cutoff for the lowest-dose group of estimated antibody dose, and the corresponding solid lines show the cutoff for the middle-dose group (Spearman’s rho = 0.425; P<0.001). Panel C shows the adjusted odds ratio for death between days 3 and 16 after diagnosis among 71 patients 16 years of age or older. The analysis used the lowest-dose group as the reference group, with adjustment for age and pretransfusion cycle-threshold value. I bars indicate 95% confidence intervals. Patients who died before day 3 after the diagnosis of EBOV disease were excluded., In a test for association assuming a linear trend, after adjustment for age and cycle threshold, P = 0.21 for IgG and P = 0.32 for neutralizing antibodies. Panel D shows the change in EBOV cycle-threshold values from before to after transfusion among 83 patients 16 years of age or older. The analysis used the lowest-dose group as the reference group, with adjustment for age and pretransfusion cycle-threshold value. The cycle-threshold value is the number of cycles required for the fluorescence signal to cross the threshold for a positive result on the EBOV polymerase-chain-reaction assay; lower values indicate higher viral loads. I bars indicate 95% confidence intervals. More patients were included in this analysis than in the mortality analysis (see the Supplementary Appendix). In tests for heterogeneity between the dose groups (with adjustment for age and pretransfusion cycle-threshold value), P = 0.02 for IgG and P = 0.82 for neutralizing antibodies. In a test for a linear trend (with adjustment for age and pretransfusion cycle-threshold values), P = 0.06 for IgG and P = 0.69 for neutralizing antibodies.

Comment on

  • Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea.
    van Griensven J, Edwards T, de Lamballerie X, Semple MG, Gallian P, Baize S, Horby PW, Raoul H, Magassouba N, Antierens A, Lomas C, Faye O, Sall AA, Fransen K, Buyze J, Ravinetto R, Tiberghien P, Claeys Y, De Crop M, Lynen L, Bah EI, Smith PG, Delamou A, De Weggheleire A, Haba N; Ebola-Tx Consortium. van Griensven J, et al. N Engl J Med. 2016 Jan 7;374(1):33-42. doi: 10.1056/NEJMoa1511812. N Engl J Med. 2016. PMID: 26735992 Free PMC article. Clinical Trial.

References

    1. van Griensven J, Edwards T, de Lamballerie X, et al. Evaluation of convalescent plasma for Ebola virus disease in Guinea. N Engl J Med. 2016;374:33–42. - PMC - PubMed
    1. Edwards T, Semple MG, De Weggheleire A, et al. Design and analysis considerations in the Ebola_Tx trial evaluating convalescent plasma in the treatment of Ebola virus disease in Guinea during the 2014-2015 outbreak. Clin Trials. 2016;13:13–21. - PMC - PubMed

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