Antivenom Distribution Research Articles

Therapeutic itineraries of snakebite victims and antivenom access in southern Mexico.

Access to antivenoms in cases of snakebite continues to be an important public health issue around the world, especially in rural areas with poorly developed health care systems. This study aims to evaluate therapeutic itineraries and antivenom accessibility following snakebites in the states of Oaxaca and Chiapas in southern Mexico. Employing an intercultural health approach that seeks to understand and bridge allopathic and traditional medical perceptions and practices, we conducted field interviews with 47 snakebite victims, documenting the therapeutic itineraries of 54 separate snakebite incidents that occurred between 1977 and 2023. Most victims used traditional remedies as a first line of treatment, often to withstand the rigors of a long journey to find antivenoms. The main obstacles to antivenom access were distance, poor antivenom availability, and cost. Standard antivenom treatment is highly valued and sought after, even as traditional beliefs and practices persist within a cultural framework known as the "hot-cold" system. The findings are crucial for informing future enhancements to antivenom distribution systems, health education initiatives, and other interventions aimed at mitigating the impact of snakebites in the region.

Identifying high snakebite risk area under climate change for community education and antivenom distribution

Snakebite is one of the largest risks from wildlife, however little is known about venomous snake distribution, spatial variation in snakebite risk, potential changes in snakebite risk pattern due to climate change, and vulnerable human population. As a consequence, management and prevention of snakebite is hampered by this lack of information. Here we used habitat suitability modeling for 10 medically important venomous snakes to identify high snakebite risk area under climate change in Iran. We identified areas with high snakebite risk in Iran and showed that snakebite risk will increase in some parts of the country. Our results also revealed that mountainous areas (Zagros, Alborz, Kopet–Dagh mountains) will experience highest changes in species composition. We underline that in order to improve snakebite management, areas which were identified with high snakebite risk in Iran need to be prioritized for the distribution of antivenom medication and awareness rising programs among vulnerable human population.

Mitigating the chronic burden of snakebite: turning the tide for survivors

The International Snakebite Awareness Day has taken place annually on Sept 19 since 2018. Snakebites kill an estimated 137 880 people each year and three times as many survivors live with life-changing disabilities.1 The high burden of snakebite in south and southeast Asia, Africa, and Latin America came to global attention in 2017 when WHO recognised snakebite envenoming as a neglected tropical disease (NTD).2 One key issue is the development, production, and distribution of antivenoms. Since 2018, there has been some increased funding for research and development of antivenoms and other therapies.

Snakebites in "Invisible Populations": A cross-sectional survey in riverine populations in the remote western Brazilian Amazon.

In the Brazilian Amazon, long distances, low healthcare coverage, common use of ineffective or deleterious self-care practices, and resistance to seeking medical assistance have an impact on access to antivenom treatment. This study aimed to estimate snakebite underreporting, and analyze barriers that prevent victims from obtaining healthcare in communities located in 15 municipalities on the banks of the Solimões, Juruá and Purus Rivers, in the remote Western Brazilian Amazon. Information on the participants' demographics, previous snakebites, access to healthcare, time taken to reach medical assistance, use of self-care practices, and the reason for not accessing healthcare were collected through semi-structured interviews. In the case of deaths, information was collected by interviewing parents, relatives or acquaintances. A total of 172 participants who reported having suffered snakebites during their lifetime were interviewed. A total of 73 different treatment procedures was reported by 65.1% of the participants. Participants living in different river basins share few self-care procedures that use traditional medicine, and 91 (52.9%) participants reported that they had access to healthcare. Living in communities along the Juruá River [OR = 12.6 (95% CI = 3.2-49.7; p<0.001)] and the use of traditional medicine [OR = 11.6 (95% CI = 3.4-39.8; p<0.001)] were variables that were independently associated to the lack of access to healthcare. The main reasons for not accessing healthcare were the pprioritization of traditional treatments (70.4%), and the failure to recognize the situation as being potentially severe (50.6%). Four deaths from complications arising from the snakebite were reported, and three of these were from communities on the banks of the Juruá River. Only one of these received medical assistance. We found an unexpectedly high underreporting of snakebite cases and associated deaths. Snakebite victims utilized three main different healing systems: 1) self-care using miscellaneous techniques; 2) official medical healthcare generally combined with traditional practices; and 3) self-care using traditional practices combined with Western medicines. To mitigate snakebite burden in the Brazilian Amazon, an innovative intervention that would optimize timely delivery of care, including antivenom distribution among existing community healthcare centers, is needed.

Addressing the global snakebite crisis with geo-spatial analyses – Recent advances and future direction

Venomous snakebite is a neglected tropical disease that annually leads to hundreds of thousands of deaths or long-term physical and mental ailments across the developing world. Insufficient data on spatial variation in snakebite risk, incidence, human vulnerability, and accessibility of medical treatment contribute substantially to ineffective on-ground management. There is an urgent need to collect data, fill knowledge gaps and address on-ground management problems. The use of novel, and transdisciplinary approaches that take advantage of recent advances in spatio-temporal models, ‘big data’, high performance computing, and fine-scale spatial information can add value to snakebite management by strategically improving our understanding and mitigation capacity of snakebite. We review the background and recent advances on the topic of snakebite related geospatial analyses and suggest avenues for priority research that will have practical on-ground applications for snakebite management and mitigation. These include streamlined, targeted data collection on snake distributions, snakebites, envenomings, venom composition, health infrastructure, and antivenom accessibility along with fine-scale models of spatio-temporal variation in snakebite risk and incidence, intraspecific venom variation, and environmental change modifying human exposure. These measures could improve and ‘future-proof’ antivenom production methods, antivenom distribution and stockpiling systems, and human-wildlife conflict management practices, while simultaneously feeding into research on venom evolution, snake taxonomy, ecology, biogeography, and conservation.

Retrospective hospital-based study on snakebite envenomation in Sudan.

BackgroundSnakebite statistics are lacking in Sudan despite the high estimated burden. In this study we aimed to describe the incidence of snakebite envenomation and death in Sudan and to show the state-wise distribution of snakebite episode.MethodsWe retrospectively analyzed hospital-based data on snakebite for 2014–2018. Data were obtained from the annual health statistical reports of the Ministry of Health. Descriptive statistics were used to illustrate the results.ResultsA total of 63 160 people were envenomed during 2014–2018 with an average of 12 632 cases/year. The death rate between inpatient cases was 2.5%. The annual incidence was 18– 47 cases/100 000 population. Gadarif state recorded the highest incidence (132/100 000 population) of snakebite envenomation in Sudan whereas Northern state had the least incidence (5/100 000 population). The 15–24 y age group experienced the highest risk of snakebite and males were more exposed to snakebites than females.ConclusionsAlthough hospital-based records underestimate the burden of snakebite, they can still provide an insight regarding the actual numbers. Here, we highlight the at-risk states in Sudan to be targeted for further questionnaire-based epidemiological studies and to guide health authorities to reduce the burden of snakebite envenomation by insuring proper antivenom distribution to the highly affected areas.

Snake Bite Management: A Scoping Review of the Literature.

Background:Around the world, snake bite envenomation remains an underreported human health hazard. Envenomation can cause local and systemic complications, especially when there is a lack of antivenom availability. Although there are established guidelines regarding snake bite management acute care, there is a paucity of data regarding surgical intervention and the plastic surgeon’s role treating this unique patient population.Methods:A review was conducted identifying relevant published articles involving snake bite management and treatment in PubMed and EMBASE.Results:One hundred ten articles were identified and 77 met inclusion criteria. Snake bite envenomation can result in complications that are dependent upon a variety of variables. The literature has shown the best field treatment to be timely transportation to the nearest medical facility, along with antivenom administration. The cytotoxic, hemotoxic, and neurotoxic effects of venom can cause a variety of local soft tissue and systemic complications. Surgical interventions such as fasciotomies, wound debridements, skin grafts, and tissue flaps may be necessary in these patients to optimize functional and aesthetic outcomes. Disparities in access to care in resource limited settings are discussed.Conclusions:Global health disparities and insufficient antivenom distribution create an inequality of care in snake bite patients. Plastic surgeons have an important role in managing acute and chronic complications of snake bite envenomations that can lead to improved patient outcomes.

Overview of snakebite in Brazil: Possible drivers and a tool for risk mapping.

Snakebite envenoming affects close to 2.7 million people globally every year. In Brazil, snakebites are reported to the Ministry of Health surveillance system and cases receive antivenom free of charge. There is an urgent need to identify higher risk areas for antivenom distribution, and to develop prevention activities. The objective of this study is to provide an overview of the epidemiological situation of snakebite envenoming in Brazil and explore possible drivers; as well as to create a flowchart tool to support decision-makers identify higher risk areas. An ecological-type study was carried out using data by municipality (2013–2017). Study parts: 1) Create a geocoded database and perform a descriptive and cluster analysis; 2) Statistical analysis to measure the association of snakebite and possible environmental and socioeconomic drivers; 3) Develop a flowchart to support decision-makers and the application of this tool in one state (Rio Grande do Sul) as an example. An average of 27,120 snakebite cases per year were reported at the country level. Clusters of municipalities with high numbers of snakebites are mostly found in the Amazon Legal Region. The negative binomial regression model showed association with the snakebite case count: the type of major habitat, tropical or non-tropical; temperature; percentage of urbanization; precipitation; elevation; GDP per capita; a weaker relation with forest loss; and with venomous snake richness. The state where the instrument was applied reported 4,227 snakebites in the period. Most municipalities were considered as medium risk and 56/496 as high risk according to the tool created. Snakebite cases are distributed across the entire country with the highest concentration in the Legal Amazon Region. This creates a complex situation both for better understanding of the association of environmental and socioeconomic factors with snakebites and for the distribution and maintenance of antivenom to remote areas. Research into types of antivenom with a longer shelf life without the need for refrigeration is needed.

Bushmaster bites in Brazil: ecological niche modeling and spatial analysis to improve human health measures

In 2017, the World Health Organization has included ophidian accidents in category A of the list of neglected tropical diseases, i.e. with a high impact on world health and that do not receive the necessary attention. It is fundamental that the combat to this health issue becomes a priority and be developed through the cooperation of different areas of knowledge. Our goals were to identify the potential geographical distribution of Lachesis muta (bushmaster snake) for supporting the planning of the distribution of antivenom in Brazil and mitigate this disease. Occurrence records of the species were taken from scientific collections. The data of antivenom distribution were obtained from the Ministry of Health and State Secretaries of Health. Our results showed climatic suitability for L. muta in 60% of the Brazilian territory, including Amazon and Atlantic Forest Biomes. The highest incidence rates and suitability values were recorded for the North region, which is a priority for mitigate this disease. Our results can reduce unnecessary expense and support the efficient distribution of the antivenom medication. We encourage mapping the importance medical animals for recognize areas of occurrence of neglected diseases to improve human health measures.

POTENTIAL GEOGRAPHIC DISTRIBUTION OF THE GENUS Micrurus WAGLER, 1824 (SERPENTES: ELAPIDAE) AND ANTIVENOM SUPPLY IN RIO DE JANEIRO STATE, BRAZIL

The coral snake genus Micrurus has non-aggressive behavior, being responsible for only 0.4% of the reports of snakebites in Brazil. However, although rare, accidents are potentially serious due to rapidly evolving respiratory paralysis. In the last few years, there was an abrupt reduction in the number of hospitals receiving antivenom support in Rio de Janeiro State, and currently the Health Ministry of Brazil distributes the antivenom only to 25 hospitals in 21 municipalities, even so with no data on specific serum provided by each hospital. This study aimed to determine the potential distribution of Micrurus species in Rio de Janeiro State in order to compare potential areas for risk of elapidic accidents with the localities assisted by hospitals with antivenom distribution. We performed ecological niche models to generate maps of potential distribution for all species through several niche algorithms. Based on these results we analyzed and discussed the consequences of this change in the number of hospitals receiving antivenom. Our results revealed the potential occurrence of the genus throughout the State territory and show a partially homogeneous distribution of health units, although the northern region represents an area with a deficiency in hospital coverage. According to our results and data from the Rio de Janeiro State Secretary of Health, it is highly desirable that at least some antivenom service centers in the regions “Metropolitana” and “Baixadas Litorâneas” receive antielapidic serum and that there be an increase in the number of units in “Norte Fluminense” and “Noroeste Fluminense” regions of Rio de Janeiro State.

A comprehensive approach to managing a neglected, neglected tropical disease; The Myanmar Snakebite Project (MSP).

Snakebite is predominantly an occupational disease affecting poor rural farmers in tropical regions and was recently added to the World Health Organisation list of Neglected Tropical Diseases (NTD). We document an overview of methodologies developed and deployed in the Myanmar Snakebite Project, a foreign aid project largely funded by the Australian Government, with the core aim to “improve outcomes for snakebite patients”. A multidisciplinary team of experts was assembled that worked in a collaborative manner with colleagues in Myanmar, first to identify problems related to managing snakebite and then develop interventions aimed to improve selected problem areas. A broad approach was adopted, covering antivenom production, antivenom distribution and health system management of snakebite. Problems identified in antivenom production included poor snake husbandry resulting in poor survival of captive specimens, lack of geographical diversity; poor horse husbandry, resulting in high mortality, inadequate stock acquisition protocols and data collection, and inappropriate immunisation and bleeding techniques; and inadequate production capacity for freeze dried antivenoms and quality control systems. These problems were addressed in various ways, resulting in some substantial improvements. Antivenom distribution is being reorganised to achieve better availability and utilisation of stock. Health system management of snakebite was assessed across all levels within the area selected for the study, in Mandalay region. A comprehensive community survey indicated that hospital statistics substantially underestimated the snakebite burden, and that access to care by local villagers was delayed by transport and cost issues compounded by lack of antivenom at the most peripheral level of the health service. A health system survey confirmed under-resourcing at the local village level. Prospective case data collection initiated at tertiary hospitals indicated the extent of the snakebite burden on health resources. Interventions initiated or planned include training of health staff, development of a core of senior trainers who can “train the trainers” nationwide in a sustainable way, development and deployment of management guidelines and algorithms for snakebite and a distribution of solar powered fridges to remote health facilities to allow storage of antivenom and prompt treatment of snakebite cases before transfer to major hospitals, thereby reducing the “bite to needle” time.

Accidentes por animales ponzoñosos en el norte de la provincia de la pampa, argentina. Estudio epidemiológico

They are of compulsory report in our country, because they produce serious consequences in Public Health. This project aims to epidemiologically describe accidents caused by poisonous animals in the north of La Pampa, identify the areas of highest risk and relate them to the distribution antivenoms centers and health institutions with intensive care. A retrospective descriptive epidemiological study was carried out to collect information about accidents with poisonous in the north of La Pampa province during the period 2005-2017. Primary and secondary data sources were used. A review of C2 reports of poisonous accidents from National Health Surveillance System (NHSS) and from records of the Dangerous Species for human and animal health Identification Services from FCV-UNLPam was carried out. Twentyeight interviews to community references and 10 health teams were done. According to the NHSS data, 6 cases of alacrism, 21 of arachnoidism and 3 of ophidism were recorded in the study period. According to the interviews, cases of poisonous animal accidents were described in different locations. The distribution centers of antivenoms, are according to the areas where the accidents were recorded. From the analysis of the data in the study period, we can conclude there are more underreporting than cases reported to the NHSS. In situations where data on accidents by venomous species are deficient, it is difficult to accurately determine the antidotes. This leads national health authorities to underestimate these needs, thereby reducing the distribution of anti-venoms. For this reason, it is important to strengthen the notification, systematization and dissemination of information to contribute to the monitoring and implementation of prevention measures and the treatment of accidents.

Experimental Lachesis muta rhombeata envenomation and effects of soursop (Annona muricata) as natural antivenom.

BackgroundIn the Atlantic forest of the North and Northeast regions of Brazil, local population often uses the fruit juice and the aqueous extract of leaves of soursop (Annona muricata L.) to treat Lachesis muta rhombeata envenomation. Envenomation is a relevant health issue in these areas, especially due to its severity and because the production and distribution of antivenom is limited in these regions. The aim of the present study was to evaluate the relevance of the use of soursop leaf extract and its juice against envenomation by Lachesis muta rhombeata.MethodsWe evaluated the biochemical, hematological and hemostatic parameters, the blood pressure, the inflammation process and the lethality induced by Lachesis muta rhombeata snake venom. We also assessed the action of the aqueous extract of leaves (AmL) and juice (AmJ) from A. muricata on the animal organism injected with L. m. rhombeata venom (LmrV) in the laboratory environment.ResultsLmrV induced a decrease of total protein, albumin and glucose; and increase of creatine kinase, aspartate aminotransferase, and urea concentrations. It provoked hemoconcentration followed by reduction of hematocrit, an increase in prothrombin time and partial thromboplastin time and a decrease of the blood pressure. LmrV induced the release of interleukin-6, an increase in neutrophils and changes in the serum protein profile, characteristic of the acute inflammatory process. LD50 values were similar for the groups injected with LmrV and treated or untreated with AmJ and AmL. Both treatments play a role on the maintenance of blood glucose, urea and coagulation parameters and exert a protective action against the myotoxicity. However, they seem to worsen the hypotension caused by LmrV.ConclusionThe treatments with AmJ and AmL present some beneficial actions, but they might intensify some effects of the venom. Therefore, additional studies on A. muricata are necessary to enable its use as natural antivenom for bushmaster snakebite.

Appraisal of snakebite incidence and mortality in Bolivia

No information has been yet published on snakebite in Bolivia. The country includes very different ecological situations leading to various epidemiological risks. A study has been carried out to evaluate the incidence and location of snakebite, particularly in relation with altitude, in order to improve management. Investigations on snakebite epidemiology were based on a) cases treated in health facilities as reported by health authorities and b) household surveys carried out in areas with high variations of altitude, in various regions of Bolivia. An average of 700 bites was treated each year in Bolivia (national annual incidence = 8 bites per 100,000 people) with a great disparity between districts. Household surveys showed annual incidences ranged from 30 to 110 bites per 100,000 inhabitants depending on location. Annual mortality ranged 0.1–3.9 per 100,000 people. A significant and constant inverse correlation was shown between snakebite incidence and altitude, which may be explained by both snake and human distributions and activities. Notification of snakebite is useful for improving patient management and informing antivenom distribution. It should also involve the report of deaths and clinical details of envenomation.

Role of the animal model on the pharmacokinetics of equine-derived antivenoms

Antivenom pharmacokinetics has been studied in heterologous models in which the animal species used as immunoglobulin source is different from that used as recipient. In these models, after intravenous administration of antivenom, the plasma concentration of immunoglobulins shows a rapid initial declining-phase followed by a slower terminal-phase, which has been associated with antivenom distribution and elimination, respectively. We have compared pharmacokinetic parameters for equine-derived antivenom in homologous (horse) and heterologous (cow) models. It was found that the maximum concentration is lower in cows than in horses. Additionally, the steady-state distribution volume is higher in cows as compared to horses. On the other hand, models were not different in the time required to reach the maximum concentration, the area under the concentration/time curve, the half-life of decay during the slowest phase, the systemic clearance and the mean residence time. Similar results were obtained in a rabbit model, in which the pharmacokinetics was also affected by passive immunization of rabbits with anti-equine IgG. We conclude that, in addition to other physiological differences (e.g. cardiac frequency, plasmatic volume, glomerular filtration rate, etc.) between animal models, the ability to remove foreign immunoglobulins might influence the way in which the plasma concentration of antivenom decreases over time, thereby distorting the pharmacokinetic predictions based on non-compartmental models.

Snakebite Mortality in India: A Nationally Representative Mortality Survey

BackgroundIndia has long been thought to have more snakebites than any other country. However, inadequate hospital-based reporting has resulted in estimates of total annual snakebite mortality ranging widely from about 1,300 to 50,000. We calculated direct estimates of snakebite mortality from a national mortality survey.Methods and FindingsWe conducted a nationally representative study of 123,000 deaths from 6,671 randomly selected areas in 2001–03. Full-time, non-medical field workers interviewed living respondents about all deaths. The underlying causes were independently coded by two of 130 trained physicians. Discrepancies were resolved by anonymous reconciliation or, failing that, by adjudication.A total of 562 deaths (0.47% of total deaths) were assigned to snakebites. Snakebite deaths occurred mostly in rural areas (97%), were more common in males (59%) than females (41%), and peaked at ages 15–29 years (25%) and during the monsoon months of June to September. This proportion represents about 45,900 annual snakebite deaths nationally (99% CI 40,900 to 50,900) or an annual age-standardised rate of 4.1/100,000 (99% CI 3.6–4.5), with higher rates in rural areas (5.4/100,000; 99% CI 4.8–6.0), and with the highest state rate in Andhra Pradesh (6.2). Annual snakebite deaths were greatest in the states of Uttar Pradesh (8,700), Andhra Pradesh (5,200), and Bihar (4,500).ConclusionsSnakebite remains an underestimated cause of accidental death in modern India. Because a large proportion of global totals of snakebites arise from India, global snakebite totals might also be underestimated. Community education, appropriate training of medical staff and better distribution of antivenom, especially to the 13 states with the highest prevalence, could reduce snakebite deaths in India.

Stability, distribution and use of antivenoms for snakebite envenomation in Latin America: Report of a workshop

The issues of antivenom stability and distribution, and the training of health staff in the correct use of antivenoms in Latin America were discussed in a workshop held at Instituto Clodomiro Picado, Costa Rica, in September 16–19, 2008, under the auspices of the program CYTED. Participants from public antivenom production laboratories of the region, together with representatives of the Ministries of Health, from Argentina, Paraguay, Brazil, Bolivia, Perú, Ecuador, Colombia, Venezuela, Panamá, Costa Rica and Nicaragua participated in the event. Technical advances in the study of antivenom stability and in the design of novel formulations aimed at generating products of higher stability were presented. In addition, antivenom acquisition and distribution systems in every country were presented and discussed, together with novel tools that could be useful for improving antivenom distribution, such as the software SIGEpi, developed by the Pan American Health Organization. The issue of the cold chain, as well as the most frequent causes of misuse of antivenoms in the region, were also analyzed. Finally, the experiences of training programs for health staff on the correct use of antivenoms in snakebite envenomation treatment in Latin America were presented. It was concluded that, in addition to the fostering of antivenom production and quality control, renewed efforts should be implemented at improving the stability, distribution and correct use of antivenoms in the region.

Strengthening antivenom production in Central and South American public laboratories: Report of a workshop

A workshop on antivenom production in Central and South American public laboratories was performed at Instituto Butantan, Sao Paulo, Brazil, from June 12 to June 16, 2006, under the auspices of the program CYTED. The activity was attended by representatives of public laboratories from Costa Rica, Colombia, Perú, Bolivia, Brazil, and Uruguay. Representatives of the World Health Organization (WHO) and the Brazilian Ministry of Health also participated in the workshop. The political, institutional and technological issues related with antivenom manufacture and distribution in these countries were discussed. Current problems on antivenom production and distribution were analyzed, and the need to strengthen collaborative links between countries was stressed, particularly regarding training programs, transfer of technology, and distribution of antivenoms, with the involvement of the Pan American Health Organization and the WHO. Future workshops on other relevant issues, such as quality control and regulatory policies, are being planned, together with collaborative research efforts between the laboratories.

Pharmacokinetics of whole IgG equine antivenom: Comparison between normal and envenomed rabbits

Pharmacokinetics of antivenoms has been mainly studied in normal animals, whereas very little is known on pharmacokinetics in envenomed animals. The aim of this study was to compare pharmacokinetic parameters of whole IgG equine antivenom in normal rabbits and in rabbits suffering a moderate envenoming by intramuscular injection of the venom of the viperid snake Bothriechis lateralis, which induces drastic microvascular alterations. Anti- Micrurus nigrocinctus antivenom was used, instead of polyvalent (Crotalinae) antivenom, to avoid the formation of toxin–antibody complexes which may alter antivenom pharmacokinetics. It was thus possible to study the effect of vascular alterations, i.e., edema and hemorrhage, induced by the venom on IgG antivenom distribution and elimination. An ELISA was utilized to quantify equine IgG antivenom concentration in rabbit serum. In addition, the amount of IgG antivenom extravasated in injected muscles was also determined. Results indicate that there were no significant differences, between control and envenomed rabbits, in any of the pharmacokinetic parameters investigated, thus suggesting that a moderate envenoming by this viperid species does not alter the pharmacokinetics of IgG antivenom. A significantly higher amount of antivenom IgG was observed in muscle from envenomed rabbits than in muscle from control animals. However, this corresponds to a low percentage of the administered antivenom and, therefore, this increased local extravasation does not have a significant impact in the overall antivenom pharmacokinetics.

Assessment of efficacy of bothropic antivenom therapy on microcirculatory effects induced by Bothrops jararaca snake venom

Intravenous administration of antibothropic antivenom (BAv) neutralises the systemic effects, but does not efficiently reverse the local symptoms elicited by the Bothrops jararaca venom (BjV). The mechanisms involved in this poor protection have not been clarified. In this work, intravital microscopy studies were carried out to determine the efficacy of different schedules of BAv treatment on local effects evoked by topical application of BjV in the microcirculatory network of the internal spermatic fascia of Wistar rats. Results demonstrated that BAv administration 15 min before, simultaneously with, or 15 min after BjV application did not totally reverse the local symptoms, represented by disturbances of coagulation, development of haemorrhage lesions, vascular permeability increase and increment on leukocyte–endothelium interactions. This lack of effectiveness neither reflects an inadequate amount of specific antibodies in the antivenom against toxins responsible for local effects nor an insufficient dose of circulating BAv during the assays. Administration of fluorescein isothiocyanate (FITC) labelled-BAv showed the dynamics of distribution of the antivenom in the microcirculatory network. Images obtained from prior and simultaneously treated animals showed that the antivenom remains at luminal side of vessels before venom application, and the latency time to antivenom leakage is coincidental to that for local effects evoked by the venom. In addition, images from posterior treatment demonstrated that the intense alterations in the microcirculatory network impair antivenom distribution at the site of injection. Together, our data show that the lack of effectiveness of antivenom therapy is due to impaired and delayed venom and antivenom interaction at the site of injury.