@article{fdi:010081308,
  title = {{S}ingle-arm, multicenter phase {I}/{II} clinical trial for the treatment of envenomings by massive {A}fricanized honey bee stings using the unique apilic antivenom},
  author = {{B}arbosa, {A}. {N}. and {F}erreira, {R}. {S}. and de {C}arvalho, {F}. {C}. {T}. and {S}chuelter-{T}revisol, {F}. and {M}endes, {M}. {B}. and {M}endonca, {B}. {C}. and {B}atista, {J}. {N}. and {T}revisol, {D}. {J}. and {B}oyer, {L}. and {C}hippaux, {J}ean-{P}hilippe and {M}edolago, {N}. {B}. and {C}assaro, {C}. {V}. and {C}arneiro, {M}. {T}. {R}. and de {O}liveira, {A}. {P}. {P}. and {P}imenta, {D}. {C}. and da {C}unha, {L}. {E}. {R}. and dos {S}antos, {L}. {D}. and {B}arraviera, {B}.},
  editor = {},
  language = {{ENG}},
  abstract = {{W}e evaluated the safety, optimal dose, and preliminary effectiveness of a new-approach {A}fricanized honeybee ({A}pis mellifera) {A}ntivenom ({AAV}) in a phase {I}/{II}, multicenter, non-randomized, single-arm clinical trial involving 20 participants with multiple stings. {P}articipants received 2 to 10 vials of {AAV} depending on the number of stings they suffered, or a predefined adjuvant, symptomatic, and complementary treatment. {T}he primary safety endpoint was the occurrence of early adverse reactions within the first 24 h of treatment. {P}reliminary efficacy based on clinical evolution, including laboratory findings, was assessed at baseline and at various time points over the four following weeks. {ELISA} assays and mass spectrometry were used to estimate venom pharmacokinetics before, during, and after treatment. {T}wenty adult participants, i.e., 13 (65%) men and 7 (35%) women, with a median age of 44 years and a mean body surface area of 1.92 m(2) (median = 1.93 m(2)) were recruited. {T}he number of stings ranged from 7 to > 2,000, with a median of 52.5. {S}ymptoms of envenoming were classified as mild, moderate, or severe in 80% (16), 15% (3), and 5% (1) of patients, respectively; patients with mild, moderate, or severe envenoming received 2, 6, and 10 vials of {AAV} as per the protocol. {N}one of the patients had late reactions (serum sickness) within 30 d of treatment. {T}here was no discontinuation of the protocol due to adverse events, and there were no serious adverse events. {O}ne patient had a moderate adverse event, transient itchy skin, and erythroderma. {A}ll participants completed the intravenous antivenom infusion within 2 h, and there was no loss to follow-up after discharge. {ELISA} assays showed venom (melittin and {PLA}(2)) concentrations varying between 0.25 and 1.479 ng/m{L} prior to treatment. {V}enom levels decreased in all patients during the hospitalization period. {S}urprisingly, in nine cases (45%), despite clinical recovery and the absence of symptoms, venom levels increased again during outpatient care 10 d after discharge. {M}ass spectrometry showed melittin in eight participants, 30 d after treatment. {C}onsidering the promising safety results for this investigational product in the treatment of massive {A}fricanized honeybee attack, and its efficacy, reflected in the clinical improvements and corresponding immediate decrease in blood venom levels, the {AAV} has shown to be safe for human use.},
  keywords = {antivenom ; {A}pis mellifera ({A}fricanized) ; clinical trial ; safety ; assessment ; enzyme-linked immunosorbent assay ({ELISA}) ; {BRESIL}},
  booktitle = {},
  journal = {{F}rontiers in {I}mmunology},
  volume = {12},
  numero = {},
  pages = {653151 [14 p.]},
  ISSN = {1664-3224},
  year = {2021},
  DOI = {10.3389/fimmu.2021.653151},
  URL = {https://www.documentation.ird.fr/hor/fdi:010081308},
}