TY - JOUR
T1 - A clinical trial protocol to treat massive Africanized honeybee (Apis mellifera) attack with a new apilic antivenom
AU - Barbosa, Alexandre Naime
AU - Boyer, Leslie
AU - Chippaux, Jean Philippe
AU - Medolago, Natalia Bronzatto
AU - Caramori, Carlos Antonio
AU - Paixão, Ariane Gomes
AU - Poli, João Paulo Vasconcelos
AU - Mendes, Mônica Bannwart
AU - dos Santos, Lucilene Delazari
AU - Ferreira, Rui Seabra
AU - Barraviera, Benedito
N1 - Funding Information:
The authors would like to thank the Clinical Research Unit (UPECLIN) of Botucatu Medical School of UNESP, Marcia Tonin Rigotto Carneiro and Ricardo Oliveira Orsi (FAPESP grant, process n. 2012/23466-2) for their support. Thanks are also due to the Center for the Study of Venoms and Venomous Animals (CEVAP) of UNESP for enabling the publication of this paper (Edital Toxinologia CAPES no. 063/2010, Process no. 230.38.006285/ 2011-21, AUXPE Toxinologia 1219/2011). Funding This study was partially supported by funds from the São Paulo Research Foundation (FAPESP) granted to RSF Jr. (process n. 2012/08101-8), and from the National Council for Scientific and Technological Development (CNPq) granted to BB (process n. 401170/2013-6). This work was also supported by the Coordination for the Improvement of Higher Education Personnel (CAPES) through Edital Toxinologia n. 063/2010, process n. 230.38.006285/ 2011-21, AUXPE Toxinologia 1219/2011 and by the Department of Science and Technology (DECIT) and the Secretariat of Science, Technology and Strategic Inputs (SCTIE), CNPq process n. 401170/2013-6, of the Brazilian Ministry of Health. RSF Jr. is a CNPq DTI fellow researcher (310395/2014-3).
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/3/16
Y1 - 2017/3/16
N2 - Background: Envenomation caused by multiple stings from Africanized honeybees Apis mellifera constitutes a public health problem in the Americas. In 2015, the Brazilian Ministry of Health reported 13,597 accidents (incidence of seven cases per 100,000 inhabitants) with 39 deaths (lethality of 0.25%). The toxins present in the venom, which include melittin and phospholipase A2, cause lesions in diverse organs and systems that may be fatal. As there has been no specific treatment to date, management has been symptomatic and supportive only. Methods: In order to evaluate the safety and neutralizing capacity of a new apilic antivenom, as well as to confirm its lowest effective dose, a clinical protocol was developed to be applied in a multicenter, non-randomized and open phase I/II clinical trial. Twenty participants with more than five stings, aged more than 18 years, of both sexes, who have not previously received the heterologous serum against bee stings, will be included for 24 months. The proposed dose was based on the antivenom neutralizing capacity and the number of stings. Treatment will be administered only in a hospital environment and the participants will be evaluated for a period up to 30 days after discharge for clinical and laboratory follow-up. Results: This protocol, approved by the Brazilian regulatory agencies for ethics (National Commission for Ethics on Research - CONEP) and sanitation (National Health Surveillance Agency - ANVISA), is a guideline constituted by specific, adjuvant, symptomatic and complementary treatments, in addition to basic orientations for conducting a clinical trial involving heterologous sera. Conclusions: This is the first clinical trial protocol designed specifically to evaluate the preliminary efficacy and safety of a new antivenom against stings from the Africanized honeybee Apis mellifera. The results will support future studies to confirm a new treatment for massive bee attack that has a large impact on public health in the Americas.
AB - Background: Envenomation caused by multiple stings from Africanized honeybees Apis mellifera constitutes a public health problem in the Americas. In 2015, the Brazilian Ministry of Health reported 13,597 accidents (incidence of seven cases per 100,000 inhabitants) with 39 deaths (lethality of 0.25%). The toxins present in the venom, which include melittin and phospholipase A2, cause lesions in diverse organs and systems that may be fatal. As there has been no specific treatment to date, management has been symptomatic and supportive only. Methods: In order to evaluate the safety and neutralizing capacity of a new apilic antivenom, as well as to confirm its lowest effective dose, a clinical protocol was developed to be applied in a multicenter, non-randomized and open phase I/II clinical trial. Twenty participants with more than five stings, aged more than 18 years, of both sexes, who have not previously received the heterologous serum against bee stings, will be included for 24 months. The proposed dose was based on the antivenom neutralizing capacity and the number of stings. Treatment will be administered only in a hospital environment and the participants will be evaluated for a period up to 30 days after discharge for clinical and laboratory follow-up. Results: This protocol, approved by the Brazilian regulatory agencies for ethics (National Commission for Ethics on Research - CONEP) and sanitation (National Health Surveillance Agency - ANVISA), is a guideline constituted by specific, adjuvant, symptomatic and complementary treatments, in addition to basic orientations for conducting a clinical trial involving heterologous sera. Conclusions: This is the first clinical trial protocol designed specifically to evaluate the preliminary efficacy and safety of a new antivenom against stings from the Africanized honeybee Apis mellifera. The results will support future studies to confirm a new treatment for massive bee attack that has a large impact on public health in the Americas.
KW - Apilic antivenom
KW - Apis mellifera
KW - Bee antivenom
KW - Bee venom
KW - Envenomation
KW - Heterologous serum
KW - Toxins
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U2 - 10.1186/s40409-017-0106-y
DO - 10.1186/s40409-017-0106-y
M3 - Article
AN - SCOPUS:85015389868
VL - 23
JO - Journal of Venomous Animals and Toxins Including Tropical Diseases
JF - Journal of Venomous Animals and Toxins Including Tropical Diseases
SN - 1678-9199
IS - 1
M1 - 14
ER -