A clinical trial protocol to treat massive Africanized honeybee (Apis mellifera) attack with a new apilic antivenom

Abstract

BackgroundEnvenomation 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.MethodsIn 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.ResultsThis 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.ConclusionsThis 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.

Honey bee envenoming in Santa Catarina, Brazil, 2007 through 2017: an observational, retrospective cohort study

“…Africanized honey bee sting incidents are a public health issue in the Americas because of the high defensiveness of the hybrid Africanized Apis mellifera 5 and the lack of a specific antivenom for the treatment 6 . As of the year 2000, the Center for the Study of Venoms and Venomous Animals of São Paulo State University (CEVAP-UNESP), in a partnership with the Vital Brazil Institute, started to develop a specific antivenom to address this issue.…”

Multiple bee stings, multiple organs involved: a case report

“…Researchers from the Center for the Study of Venoms and Venomous Animals of the São Paulo State University have provided useful perspectives regarding the treatment of honey bee attacks with evenomation and in partnership with the Vital Brazil Institute, Brazil, have developed the apilic antivenom 12 . Recently, a clinical protocol was developed for application in a multicenter non-randomized and open phase I/II clinical trial to address the safety, to determine the pharmacokinetic and proteomic profile, and confirm the lowest antivenom dose, based on the severity in each case 12 . The protocol will include participants aged >18 years; however, the inclusion of children has not yet been considered.…”

“…Improved collection of epidemiological data related to these attacks is required to ensure improved care in severe cases. Clinical trials to evaluate apilic antivenom can potentially offer perspectives on better treatment in such patients 12 .…”

Hymenoptera stings in Brazil: a neglected health threat in Amazonas State

“…Stings by insects in the order Hymenoptera are common worldwide, caused mainly by ants, bees, and wasps 1,2 . The venom released during these injuries is an important weapon against other insects and predators; however, in humans, it can cause both local, and systemic alterations, associated mainly with the deposit of the venom inoculum in the skin (bees), multiple stings (ants and wasps), or even concentration of venom (ants and bees) 3,4 .…”

“…In Brazil, accidents involving Hymenoptera are mainly caused by the genera Solenopsis and Paraponera (ants), Apis (bees), and Polistes and Mischocyttarus (wasps) 1,4,7 . The total number of accidents due to this order remains unknown, mainly due to the fact that there is no compulsory notification of cases, with the exception of bee stings, with a mean of 9,926 cases per year in the period from 2007 to 2015 4 .…”