A clinical trial protocol to treat massive Africanized honeybee (Apis mellifera) attack with a new apilic antivenom.
BACKGROUND
Envenomation caused by multiple stings from Africanized honeybeesApis melliferaconstitutes 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 honeybeeApis 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.
Department of Tropical Diseases, Botucatu Medical School, São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, SP Brazil.
Alexandre Naime
AN
Barbosa
VIPER Institute, University of Arizona College of Medicine, Tucson, AZ USA.
Leslie
L
Boyer
CERPAGE, Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Cotonou, Benin.|UMR216, Mère et enfant face aux infections tropicales and PRES Sorbonne Paris Cité, Faculté de Pharmacie, Université Paris Descartes, Paris, France.
Jean-Philippe
JP
Chippaux
Clinical Research Unit (UPECLIN), Botucatu Medical School, São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, SP Brazil.
Natalia Bronzatto
NB
Medolago
Department of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, SP Brazil.
Carlos Antonio
CA
Caramori
Department of Tropical Diseases, Botucatu Medical School, São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, SP Brazil.
Ariane Gomes
AG
Paixão
Department of Tropical Diseases, Botucatu Medical School, São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, SP Brazil.
João Paulo Vasconcelos
JPV
Poli
Department of Tropical Diseases, Botucatu Medical School, São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, SP Brazil.
Mônica Bannwart
MB
Mendes
Center for the Study of Venoms and Venomous Animals, São Paulo State University (UNESP - Univ Estadual Paulista), Av. José Barbosa de Barros, 1780, Fazenda Experimental Lageado, Botucatu, SP CEP 18.610-307 Brazil.
Lucilene Delazari
LD
Dos Santos
Department of Tropical Diseases, Botucatu Medical School, São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, SP Brazil.|Center for the Study of Venoms and Venomous Animals, São Paulo State University (UNESP - Univ Estadual Paulista), Av. José Barbosa de Barros, 1780, Fazenda Experimental Lageado, Botucatu, SP CEP 18.610-307 Brazil.
Rui Seabra
RS
Ferreira
Department of Tropical Diseases, Botucatu Medical School, São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, SP Brazil.|Center for the Study of Venoms and Venomous Animals, São Paulo State University (UNESP - Univ Estadual Paulista), Av. José Barbosa de Barros, 1780, Fazenda Experimental Lageado, Botucatu, SP CEP 18.610-307 Brazil.
Benedito
B
Barraviera
Apilic antivenom; Apis mellifera; Bee antivenom; Bee venom; Envenomation; Heterologous serum; Toxins