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

<div><p>Abstract INTRODUCTION: Hymenoptera injuries are commonly caused by stinging insects. In Amazonas state, Brazil, there is no information regarding distribution, profile, and systemic manifestations associated with Hymenoptera injuries. METHODS: This study aimed to identify risk factors for systemic manifestation using the Brazilian Notifiable Diseases Surveillance System (2007 to 2015). RESULTS: Half of Hymenoptera injuries were caused by bee stings. Hymenoptera injuries were concentrated in Manaus, and 13.36% of cases displayed systemic signs. Delayed medical assistance (4 to 12 hours) presented four times more risk for systemic manifestations. CONCLUSIONS: Simple clinical observations and history of injury are critical information for prognostic improvement.</p></div

Safety and efficacy of a freeze-dried trivalent antivenom for snakebites in the Brazilian Amazon: An open randomized controlled phase IIb clinical trial

<div><p>Background</p><p>In tropical areas, a major concern regarding snakebites treatment effectiveness relates to the failure in liquid antivenom (AV) distribution due to the lack of an adequate cold chain in remote areas. To minimize this problem, freeze-drying has been suggested to improve AV stability.</p><p>Methods and findings</p><p>This study compares the safety and efficacy of a freeze-dried trivalent antivenom (FDTAV) and the standard liquid AV provided by the Brazilian Ministry of Health (SLAV) to treat <i>Bothrops</i>, <i>Lachesis</i> and <i>Crotalus</i> snakebites. This was a prospective, randomized, open, phase IIb trial, carried out from June 2005 to May 2008 in the Brazilian Amazon. Primary efficacy endpoints were the suppression of clinical manifestations and return of hemostasis and renal function markers to normal ranges within the first 24 hours of follow-up. Primary safety endpoint was the presence of early adverse reactions (EAR) in the first 24 hours after treatment. FDTAV thermal stability was determined by estimating AV potency over one year at 56°C. Of the patients recruited, 65 and 51 were assigned to FDTAV and SLAV groups, respectively. Only mild EARs were reported, and they were not different between groups. There were no differences in fibrinogen (p = 0.911) and clotting time (p = 0.982) recovery between FDTAV and SLAV treated groups for <i>Bothrops</i> snakebites. For <i>Lachesis</i> and <i>Crotalus</i> snakebites, coagulation parameters and creatine phosphokinase presented normal values 24 hours after AV therapy for both antivenoms.</p><p>Conclusions/Significance</p><p>Since promising results were observed for efficacy, safety and thermal stability, our results indicate that FDTAV is suitable for a larger phase III trial.</p><p>Trial registration</p><p>ISRCTNregistry: ISRCTN12845255; DOI: <a href="https://doi.org/10.1186/ISRCTN12845255" target="_blank">10.1186/ISRCTN12845255</a> (<a href="http://www.isrctn.com/ISRCTN12845255" target="_blank">http://www.isrctn.com/ISRCTN12845255</a>).</p></div

Thermostability evaluations of the freeze-dried trivalent antivenom (FDTAV) at 56°C over one year.

<p>Antivenom potency for neutralizing <i>Bothrops</i>, <i>Lachesis</i> and <i>Crotalus</i> activities showed no significant decrease compared to baseline over one year of thermostability evaluations at 56°C.</p

Baseline laboratorial features of the included patients and comparison between experimental groups.

<p>Baseline laboratorial features of the included patients and comparison between experimental groups.</p

Primary efficacy endpoint analysis in <i>Bothrops</i> snakebites.

<p>Clotting time, fibrinogen and INR levels 24 hours after AV therapy in freeze-dried trivalent antivenom (FDTAV) and Ministry of Health standard liquid antivenoms (SLAVs) treated groups.</p

Epidemiological characteristics of the patients and comparison between experimental groups.

<p>Epidemiological characteristics of the patients and comparison between experimental groups.</p

Survival analysis of the primary efficacy endpoint.

<p>Time until fibrinogen (Part A) and clotting time (Part B) reaching normal values over follow-up of patients bitten by <i>Bothrops</i> snakes presented no significant difference between freeze-dried trivalent antivenom (FDTAV) and Ministry of Health standard liquid antivenoms (SLAVs) treated groups.</p

Adverse events reported in the safety study and comparison between the experimental groups.

<p>Adverse events reported in the safety study and comparison between the experimental groups.</p

Baseline clinical features of the included patients and comparison between experimental groups.

<p>Baseline clinical features of the included patients and comparison between experimental groups.</p

Flow chart of inclusion in the clinical trial.

<p>Flow chart of inclusion in the clinical trial.</p