Time to treatment and severity of snake envenoming in Brazil

Tiempo hasta el tratamiento y gravedad del envenenamiento por mordedura de ­serpiente en el Brasil

Tempo para tratamento e gravidade do envenenamento ofídico no Brasil

Yukari Figueroa Mise Rejâne Maria Lira-da-Silva Fernando Martins Carvalho About the authors

ABSTRACT

Objective

To analyze the relationship between time to treatment and severity of snakebite envenomation in Brazil.

Methods

This case-series retrospective study analyzed 144 251 snakebite cases in Brazil between 2007 and 2015, as reported to the Brazilian Notifiable Diseases Information System. The main dependent variable was snakebite envenomation severity (mild/moderate/severe). The main predictor was time to treatment (early (< 6 hours) vs. delayed (≥ 6 hours)). Covariables were snake type (Bothrops/Crotalus/Micrurus/Lachesis), patient's age and sex, bite site, and treatment at a specialized care center (center/noncenter). Polytomous logistic regression techniques were used to control the covariates and assess confounding and effect modification.

Results

The time to treatment variable was strongly associated with the severity of snakebite envenomation. Snake type and treatment at specialized care center modified the main association effect. The association between delayed time to treatment and envenomation severity was consistently stronger among patients treated at specialized care centers than among those who were not treated at such centers. Odds ratios tended to increase significantly from moderate to severe envenomation for cases within the subgroups “Center + Bothrops” (1.37 to 2.05), “No center + Bothrops” (1.25 to 1.47), “Center + Crotalus” (1.35 to 3.03), “No center + Crotalus” (0.97 to 2.72), and “Center + Lachesis” (1.22 to 1.89).

Discussion

This study confirmed the classical hypothesis that the time between snakebite and initiation of medical care is associated with severity of snakebite envenomation. It is therefore necessary to provide snakebite victims early access to specialized medical care, particularly to antivenom therapy.

Keywords
Snake bites; patient acuity; time to treatment; Brazil

RESUMEN

Objetivo

Analizar la relación entre el tiempo transcurrido hasta el tratamiento y la gravedad del envenenamiento por mordedura de serpiente (ofidismo) en el Brasil.

Métodos

En este estudio retrospectivo de una serie de casos se analizaron 144 251 casos de mordedura de serpiente en el Brasil entre el 2007 y el 2015, notificados al Sistema Brasileño de Información sobre Enfermedades de Notificación Obligatoria. La principal variable dependiente fue la gravedad del ofidismo (leve, moderado o grave). El principal factor predictivo fue el tiempo hasta el tratamiento (temprano [menos de 6 horas] o tardío [6 horas o más]). Las covariables fueron el tipo de serpiente (Bothrops, Crotalus, Micrurus o Lachesis), la edad y el sexo del paciente, la localización de la mor­dedura y el tratamiento en un centro de atención especializada (sí o no). Se usaron técnicas de regresión logística politómica para controlar las covariables y evaluar el fenómeno de confusión y la modificación del efecto.

Resultados

La variable de tiempo hasta el tratamiento se asoció estrechamente con la gravedad del ofidismo. El tipo de serpiente y el tratamiento en un centro especia­lizado modificaron el principal efecto de asociación. La asociación entre el tratamiento tardío y la gravedad del ofidismo fue sistemáticamente más estrecha en los pacientes tratados en los centros especializados de atención que entre los no tratados en tales centros. Las razones de posibilidades tendieron a aumentar significativamente del ofidismo moderado al ofidismo grave para los casos en los subgrupos “centro + Bothrops” (1,37 a 2,05), “no tratados en un centro + Bothrops” (1,25 a 1,47), “centro + Crotalus” (1,35 a 3,03), “no tratados en un centro + Crotalus” (0,97 a 2,72) y “centro + Lachesis” (1,22 a 1,89).

Discusión

Este estudio confirmó la hipótesis clásica de que el lapso entre la mordedura de serpiente y el inicio de la atención médica se asocia con la gravedad del ofidismo. Por consiguiente, es necesario dar a las víctimas de mordeduras de serpiente acceso temprano a la atención médica especializada, en particular al tratamiento con el antídoto.

Palabras clave
Mordeduras de serpientes; gravedad del paciente; tiempo de tratamiento; Brasil

RESUMO

Objetivo

Examinar a relação entre tempo para tratamento e gravidade do envenenamento ofídico no Brasil.

Métodos

Neste estudo retrospectivo de série de casos foram analisados 144.251 casos de picadas de cobras registrados no Sistema de Informação de Agravos de Notificação do Brasil entre 2007 e 2015. A principal variável dependente foi gravidade do envenenamento ofídico (leve/moderado/grave). O principal fator de predição foi tempo para tratamento (rápido <6 horas ou demorado ≥6 horas). As covariáveis foram genêro da serpente (Bothrops/Crotalus/Micrurus/Lachesis), idade e sexo do paciente, local da picada e tratamento em centro especializado de atendimento (em centro/não em centro). Um modelo de regressão logística politômica foi usado para controlar as covariáveis e avaliar os fatores de confusão e modificadores de efeito.

Resultados

A variável tempo para tratamento apresentou marcante associação com gravidade do envenenamento ofídico. O gênero da serpente e o tratamento em centro especializado modificaram o principal efeito da associação. A associação entre demora para o tratamento e gravidade do envenenamento foi consistentemente mais marcante nos casos tratados em centros especializados em comparação aos casos não tratados nestes centros. Os odds ratios tenderam a aumentar significativamente nos casos de envenenamento moderado a grave nos subgrupos “em centro + Bothrops” (1,37 a 2,05), “não em centro + Bothrops” (1,25 a 1,47), “em centro + Crotalus” (1,35 a 3,03), “não em centro + Crotalus” (0,97 a 2,72) e “em centro + Lachesis” (1,22 a 1,89).

Discussão/Conclusão

Este estudo confirmou a clássica hipótese de que o tempo decorrido entre a picada de cobra e o início do atendimento médico está associado à gravidade do envenenamento ofídico. Portanto, é necessário prover às vítimas de acidentes ofídicos acesso rápido à atenção médica especializada, sobretudo o acesso ao tratamento com soro antiofídico.

Palavras-chave
Mordeduras de serpentes; gravidade do paciente; tempo para o tratamento; Brasil

The number of snakebite envenomation victims in the Americas is high, particularly in Latin America, where it represents a serious public health problem. One study estimated that, in 2007, there was an incidence of between 80 329 and 129 084 cases in Latin America (11. Kasturiratne A, Wickremasinghe AR, De Silva N, Gunawardena NK, Pathmeswaran A, Premaratna R, et al. The global burden of snakebite: a literature analysis and modelling based on regional estimates of envenoming and deaths. PLoS Med 2008;5:e218.). In South America and Central America, there is a predominance of snakebites by the Bothrops species, while rattlesnakes (Crotalus) are responsible for most cases that occur in North America (22. Global Snakebite Initiative. Snakebite in the Americas. Available from: http://www.snakebiteinitiative.org/?page_id=699 Accessed on 2 July 2017.
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).

Snakebites in Brazil are underre­ported, and the available clinical and epidemiological data on them is often insufficient or of poor quality (33. Bochner R, Fiszon JT, Machado C. A profile of snake bites in Brazil, 2001 to 2012. J Clin Toxicol. 2014;4(3):1–7.). In Brazil, in 2007, the coefficient of snakebite incidence was relatively low (13.50 per 100 000 inhabitants), but lethality varied markedly, according to snake type (44. Brasil, Ministério da Saúde. Manual de diagnóstico e tratamento de acidentes ofídicos. Brasília: Fundação Nacional de Saúde, Coordenação de Controle de Zoonoses e Animais Peçonhentos; 2001. Available from: http://bvsms.saude.gov.br/bvs/publicacoes/funasa/manu_peconhentos.pdf Accessed on 20 June 2017.
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).

Severe and lethal snakebite cases are strongly associated with a delay in specific medical treatment (serum therapy), usually considered to be six hours following the snakebite (44. Brasil, Ministério da Saúde. Manual de diagnóstico e tratamento de acidentes ofídicos. Brasília: Fundação Nacional de Saúde, Coordenação de Controle de Zoonoses e Animais Peçonhentos; 2001. Available from: http://bvsms.saude.gov.br/bvs/publicacoes/funasa/manu_peconhentos.pdf Accessed on 20 June 2017.
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). Delayed treatment is a factor in poor prognosis. That is because even though the circulating venom is neutralized by the antivenom, this does not apply to the local lesion. Antivenom only acts on the circulating venom and does not reverse the local lesion effects caused by envenomation. This information is critical for clinical staging and envenomation treatment and prognosis (55. Spiller HA, Bosse GM, Ryan ML. Use of antivenom for snakebites reported to United States poison centers. Am J Emerg Med. 2010;28(7):780–5.).

This study aims to analyze the relationship between the time interval from snakebite to initiation of serum therapy care and the severity of snakebite envenomation in patients in Brazil.

MATERIAL AND METHODS

This case-series retrospective study ­included all 144 251 snakebite envenomation cases caused by snakes of medical importance, compulsorily reported to the Brazilian Notifiable Diseases Information System (Sistema de Informação de Agravos de Notificação ­(SINAN)), that occurred in Brazil between 2007 and 2015. The study included individuals over 15 years old, for whom the following information set was available: envenomation severity (snakebite envenomation staging); time to treatment (the interval between the snakebite and the initiation of medical care); and other covariables of interest: age, sex, snake type, anatomic region of the bite, and treatment at specialized care center. Other supportive therapies can be added to patient treatment, especially when local or systemic manifestations, such as acute renal failure, hypotension, and shock, also occur. However, the antivenom is the cornerstone of snakebite envenoming therapy.

The 144 251 cases with complete information did not differ significantly (p > 0.05, chi-square tests) from the 232 868 cases with incomplete information according to sex and anatomic region of the bite, although they did differ (p < 0.05) in terms of age, snake type, and treatment at specialized care center.

The main outcome variable (“envenomation severity”) was classified as mild, moderate, or severe. Envenomation staging is established at patient admission to the medical service, taking into account the intensity of local and/or systemic manifestations, according to Brazilian Ministry of Health criteria for the diagnosis and treatment of ophidian accidents (44. Brasil, Ministério da Saúde. Manual de diagnóstico e tratamento de acidentes ofídicos. Brasília: Fundação Nacional de Saúde, Coordenação de Controle de Zoonoses e Animais Peçonhentos; 2001. Available from: http://bvsms.saude.gov.br/bvs/publicacoes/funasa/manu_peconhentos.pdf Accessed on 20 June 2017.
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). The main predictor variable (time to treatment) was classified as early (< 6 hours) or delayed (≥ 6 hours).

The medical care at the specialized medical center should necessarily include the administration of the specific antivenom, as soon as possible (44. Brasil, Ministério da Saúde. Manual de diagnóstico e tratamento de acidentes ofídicos. Brasília: Fundação Nacional de Saúde, Coordenação de Controle de Zoonoses e Animais Peçonhentos; 2001. Available from: http://bvsms.saude.gov.br/bvs/publicacoes/funasa/manu_peconhentos.pdf Accessed on 20 June 2017.
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). Patients who did not receive antivenom therapy were classified as having a delayed time to treatment.

Dummy variables were constructed to classify the covariables: age (15 to 34 years old = 0; 35 to 59 years old = 1; and 60 years old or older = 2); snake taxon (Bothrops = 0; Crotalus = 1; Lachesis = 2; Micrurus = 3); and anatomic region of the bite (central axis = 0; upper limbs = 1; lower limbs = 2). The Brazilian Government strategy to increase accessibility to antivenom treatment ensures that municipalities either have their own specialized center for the care of victims of accidents caused by venomous animals or that the nearest center is located in a neighboring district. Patients were classified according to the place where they received their first medical care: in a specialized care center or not (center = 0; noncenter = 1). Sex was analyzed as male = 0 and female = 1. The main association, time to treatment and envenomation severity, was measured by the odds ratio (OR) and its respective 95% confidence interval (CI).

The relative importance of the main association for the covariables of patient's sex and age, treatment at specialized care center, snake taxon, and anatomic region of the bite was evaluated using polytomous logistic regression. Using the backward stepwise method, we considered the existence of confounding when the difference between the adjusted and crude ORs was 20%. Based on the scientific literature and on our data structure, interaction terms were built and tested for all the models, in order to estimate the presence of effect modification for the main association (66. Rothman KJ, Greenland S, Lash TL. Modern epidemiology. 3rd ed. Philadelphia: Lippincott, Williams & Wilkins; 2008.). Goodness-of-fit was estimated using the log likelihood ratio test, with a p value of p < 0.05.

We created a database for individual data using the Statistical Package for the Social Sciences (SPSS) version 20.0.0 (IBM Corp., Armonk, New York, United States of America) and then exported the data to Stata 12.0 (StataCorp, College Station, Texas, United States) for processing and analysis.

The data bank of cases of snakebite ­envenoming provided by the Brazilian Ministry of Health and National Health Foundation (FUNASA) did not allow ­individuals to be identified. Therefore, anonymity was preserved. The Ethical Board of the Collective Health Institute, Federal University of Bahia, approved the research project (#052/06).

RESULTS

Out of the 144 251 patients, 71 143 (49.3%) were classified as mild cases of snakebite envenomation, 61 334 (42.5%) as moderate cases, and 11 774 (8.2%) as severe cases. Delayed serum treatment (≥ 6 hours after bite) was administered to 22 483 (15.6%) of the 144 251 patients. Receiving delayed serum treatment occurred with 13.0% of the mild cases, 17.1% of the moderate cases, and 23.4% of the severe cases.

Antivenom was not used in 7 781 (5.4%) of the 144 251 patients. This was the case for 9.8% of the mild cases, 2.0% of the moderate cases, and 2.0% of the severe cases. Nonuse of antivenom occurred in 4.8% of the 130 140 patients who were attended in specialized centers, and in 10.4% of those 14 103 who were attended in other centers.

Envenomation severity was strongly (p < 0.001) associated with sex, age, snake, bite site, and treatment at a specialized care center. Within the covariable strata, severe envenomation was more frequent among males aged 60 years or over who were bitten by Micrurus in the central axis and treated at a specialized care center (Table 1).

TABLE 1
Envenomation severity according to time to treatment and relevant variables in 144 251 snakebite cases in Brazil, 2007–2015

The strength of the association between time to treatment and envenomation severity increased from the moderate cases (crude OR = 1.37; 95% CI, 1.33-1.42) to severe cases (crude OR = 2.04; 95% CI, 1.94-2.14). Crude ORs also increased from moderate cases to severe cases in those 35 to 59 years old and those 60+ and with Crotalus and Micrurus envenomation (Table 2).

TABLE 2
Crude odds ratio (OR) and respective 95% confidence interval (CI) for the association between time to treatment and envenomation severity, according to covariable strata in 144 251 snakebite cases in Brazil, 2007–2015

Polychromous logistic analysis included the variables time to treatment, envenomation severity, age, sex, bite site, treatment at specialized care center, and snake taxon. “Snake taxon” (likelihood ratio 70.33) and “treatment at a specialized care center” (likelihood ratio 11.88) modified the effect of association between time to treatment and envenomation severity. Consequently, the database was divided into the eight subgroups formed by these two covariables, in order to proceed with the appropriate ­regression analyses.

Delayed time to treatment was the only variable present in all eight subgroups. The association between delayed time to treatment and envenomation severity was consistently stronger among groups of patients treated at specialized care centers than those not treated at such centers. Further, the ORs tended to increase significantly from moderate to severe envenomation, compared to results within the subgroups “Center + Bothrops” (1.37 to 2.05), “No center + Bothrops” (1.25 to 1.47), “Center + Crotalus” (1.35 to 3.03), “No center + Crotalus” (0.97 to 2.72), and “Center + Lachesis” (1.22 to 1.89). Note that the 95% CI for “moderate” does not include the OR for the respective “severe” cases within the same subgroup. For example, in the subgroup “Center + Bothrops,” the OR = 1.37 is not included in the 1.94-2.17 95% CI of the “severe” stratum, nor is the OR = 2.05 included in the 1.32-1.42 95% CI of the “moderate” stratum (Table 3).

TABLE 3
Results of the polytomous logistic regression analysis for the association between time to treatment and envenomation severity, with odds ratio (OR) and 95% confidence interval (CI), according to snake type and treatment at specialized care center, in 144 251 snakebite cases in Brazil, 2007–2015

Covariables strata “male,” and age groups “35 to 59 years old,” and “60+ years old” also demonstrated strong associations with envenomation severity. The association between “60+ years old” and severity of Bothrops envenomation in patients treated at specialized care centers was particularly relevant. These ORs increased from 1.23 (95% CI: 1.18-1.28) among cases with moderate envenomation to 1.58 (95% CI: 1.48-1.70) among those with severe envenomation, representing a significant increase in risk of severe envenomation. Males were significantly more affected than females in Bothrops and Crotalus envenomation, but only in cases treated at specialized care centers. Further, the strength of association increased from moderate to severe cases only in cases involving “Center + Crotalus,” with the OR going from 1.14 to 1.24 (Table 3).

DISCUSSION

The variable time to treatment was strongly associated with the severity of snakebite envenomation. The Brazilian Ministry of Health has already noted the importance of time to treatment in snakebite severity (44. Brasil, Ministério da Saúde. Manual de diagnóstico e tratamento de acidentes ofídicos. Brasília: Fundação Nacional de Saúde, Coordenação de Controle de Zoonoses e Animais Peçonhentos; 2001. Available from: http://bvsms.saude.gov.br/bvs/publicacoes/funasa/manu_peconhentos.pdf Accessed on 20 June 2017.
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). A study of 9 191 snakebite cases in the Brazilian Amazon reported that, between 2007 and 2012, a delay of six or more hours in medical care was associated with increased severity of envenomation (77. Feitosa EL, Sampaio VS, Salinas JL, Queiroz AM, da Silva IM, Gomes AA, et al. Older age and time to medical assistance are associated with severity and mortality of snakebites in the Brazilian Amazon: a case-control study. PLoS One 2015;10(7):e0132237.).

Snake antivenoms are highly effective remedies (88. Brown N, Landon J. Antivenom: the most cost-effective treatment in the world? Toxicon 2010;55(7):1405–7.), but they must be adequately distributed to the necessary locations and administered by trained medical staff (99. Gutiérrez JM, Williams D, Fan HW, Warrell DA. Snakebite envenoming from a global perspective: towards an integrated approach. Toxicon 2010;56(7):1223–35.).

The Brazilian Government maintains exclusive control over antivenom production and with distribution at a reasonable cost, making it available to the entire population (1010. Chippaux JP. Control of ophidism in Brazil: a model for Africa. J Venom Anim Toxins Incl Trop Dis. 2010:16(2):188–90.). At least one antivenom center capable of providing specialized snakebite care is strategically located near every Brazilian municipality. The amount of antivenoms delivered to each center depends on epidemiological criteria, principally the number of envenomation cases the center reports to the Notifiable Diseases Information System.

According to our data, the presence of a specialized care center acted as an effect modifier, increasing the severity of snakebite envenomation. It is possible that “mild” accidents did not ­motivate patients to seek immediate specialized medical care. However, there was a delay in seeking health care once the envenomation worsened (1010. Chippaux JP. Control of ophidism in Brazil: a model for Africa. J Venom Anim Toxins Incl Trop Dis. 2010:16(2):188–90.). This process may have increased the demand of severe cases for specialized care centers.

Envenomation severity is usually associated with snake taxon. Snake venom is a complex mixture of components, such as proteins, peptides, and biologically active substances, which vary widely among the different snake types that exist on the planet (1111. Gutiérrez JM, Theakston RDG, Warrell DA. Confronting the neglected problem of snake bite envenoming: the need for a global partnership. PLoS Med. 2006;3(6):e150.). Enzymes present in the venom are related to tissue necrosis, coagulant activity, anticoagulants, and pain. Different snake types have different types of venom, which can result in distinct clinical manifestations and lethality (3, 12, 13).

In our study, snake taxon had an important modification effect on the main association between time to treatment and envenomation severity. Cases with Bothrops envenomation predominated in our case series. The genus Bothrops is ­reported to be the main etiological agent of snakebite envenomation in Brazil (33. Bochner R, Fiszon JT, Machado C. A profile of snake bites in Brazil, 2001 to 2012. J Clin Toxicol. 2014;4(3):1–7.) and Argentina (1414. Dolab JA, de Roodt AR, de Titto EH, García SI, Funes R, Salomón OD, et al. Epidemiology of snakebite and use of antivenom in Argentina. Trans R Soc Trop Med Hyg. 2014;108(5):269–76.). Bothrops asper and B. atrox cause the most bites and ­fatalities in Central and South America (22. Global Snakebite Initiative. Snakebite in the Americas. Available from: http://www.snakebiteinitiative.org/?page_id=699 Accessed on 2 July 2017.
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, 1515. Gutiérrez JM. Envenenamientos por mordeduras de serpientes en América Latina y el Caribe: una visión integral de carácter regional. Bol Malariol Salud Amb. 2011;51(1):1–22.). The genus Bothrops comprises a large number of species, which display aggressiveness and ecological plasticity and adapt to environmental changes, including anthropized environments (1616. Warrell, DA. Snake bite. Lancet. 2010;375(9708):77–88.). Crotalus snakes are found in open areas, while Lachesis is seen in dense forest environments, and these two are thus less likely to be involved in ophidian accidents (33. Bochner R, Fiszon JT, Machado C. A profile of snake bites in Brazil, 2001 to 2012. J Clin Toxicol. 2014;4(3):1–7., 44. Brasil, Ministério da Saúde. Manual de diagnóstico e tratamento de acidentes ofídicos. Brasília: Fundação Nacional de Saúde, Coordenação de Controle de Zoonoses e Animais Peçonhentos; 2001. Available from: http://bvsms.saude.gov.br/bvs/publicacoes/funasa/manu_peconhentos.pdf Accessed on 20 June 2017.
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, 1717. da Silva CJ, Jorge MT, Ribeiro LA. Epidemiology of snakebite in a central region of Brazil. Toxicon 2003;41(2):251–5.). Micrurus has a wide distribution across all of Brazil, but accidents are rare, because of its coloration (conspicuous), dentition (small, fixed, and corrugated front tusks) and the fact that they do not strike (1717. da Silva CJ, Jorge MT, Ribeiro LA. Epidemiology of snakebite in a central region of Brazil. Toxicon 2003;41(2):251–5.).

Our study revealed that the association between male sex and poisoning severity increased from moderate to severe cases for victims of Crotalus treated at specialized care centers. Men are more likely to suffer snakebites than are women, principally because of men's work in agriculture (1616. Warrell, DA. Snake bite. Lancet. 2010;375(9708):77–88., 1818. Mise YF, Lira-da-Silva RM, Carvalho FM. Agriculture and snakebite in Bahia, Brazil -an ecological study. Ann Agric Environ Med. 2016;23(3):467–70.).

In our study, snakebite envenomation was particularly severe among patients aged 60+ treated for Bothrops envenomation at specialized care centers. In the Brazilian Amazon, individuals aged 65+ presented more severe envenomation (77. Feitosa EL, Sampaio VS, Salinas JL, Queiroz AM, da Silva IM, Gomes AA, et al. Older age and time to medical assistance are associated with severity and mortality of snakebites in the Brazilian Amazon: a case-control study. PLoS One 2015;10(7):e0132237.).

Antivenom therapy was not used in 7 781 (5.4%) of reported cases. All these cases were classified as presenting “delayed” time to treatment. However, these cases only represented a tiny proportion (2.0%) of those with severe or moderate envenomation. Antivenom was not used in 4.8% of the patients who were attended at specialized centers, and in 10.8% of those who were attended at other centers. The shortage or the absence of antivenom, particularly in the specialized centers that provide health care to snakebite cases, may denote problems in the production and/or the distribution of antivenoms in the vast territory of Brazil. Or it could also indicate that the health team is not well trained about how to estimate the severity of snakebite clinical picture and, more likely, about how to administer antivenom therapy according to the recommended strength.

We should note that treatment failures cannot be attributed to nonvenomous snakebites, since this study only included cases attributed to venomous snakes from four genera occurring in Brazil: Bothrops, Crotalus, Micrurus, and Lachesis.

One positive aspect of our study is its large sample size, which allowed us to perform statistical analyses unavailable to smaller studies, such as subdividing the database in order to investigate effect modification.

Limitations inherent to cross-sectional studies may have occurred, since subjects for the study population were selected from a secondary database, sourced from compulsory notification. Since the data was not obtained from a primary source, mistakes may have occurred in the way the exposure information was obtained (information bias). Selection bias should also be considered, since this study only included cases with a complete set of variables. The study population represented only 38.3% of the 377 119 snakebite envenomation cases reported between 2007 and 2015. Further, the population presents important differences according to age group, snake type, and treatment at a specialized care center.

The study found that snake type modified the effect for the association between time to treatment and envenomation severity, although the analyses were not valid for each of the eight identified subgroups. The small sample size of certain strata decreased study power. The study classified its main outcome into three categories, which may have contributed to the smaller sample size of certain subgroups and, consequently, decreased study power.

Conclusions

This study confirmed the classical hypothesis that time to treatment is associated with snakebite envenomation severity in Brazil. Medical care at a specialized center and snake type, particularly Bothrops, Crotalus, and Lachesis, modified the effect of this association. Envenomation severity was associated with older age groups (only in envenomation by Bothrops) and with male sex (in Bothrops and Crotalus envenomation). Snakebite victims must be provided with early access to specialized medical care, particularly to antivenom therapy.

Acknowledgments

We thank the ­Brazilian Ministry of Health and FUNASA (National Health Foundation) for providing us access to the data bank that helped bring about this work.

  • Suggested citation Mise YF, Lira-da-Silva RM, Carvalho FM. Time to treatment and severity of snake envenoming in Brazil. Rev Panam Salud Publica. 2018;42:e52. https://doi.org/10.26633/RPSP.2018.52
  • Funding. Brazilian National Research Council (CNPq) grant #304563/2014-5 and FUNASA/MS (National Health Foundation, Ministry of Health, Brazil) grant # 388/2002.
  • Disclaimer. The authors hold sole responsibility for the views expressed in the manuscript, which does not necessarily reflect the opinion or policy of the RPSP/PAJPH, the Pan American Health Organization, CNPq, or FUNASA/MS. These institutions had no role in study design, data analysis, decision to publish, or preparation of the manuscript.

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History

  • Received
    25 July 2017
  • Accepted
    06 Oct 2017
  • Online publication
    28 May 2018
Organización Panamericana de la Salud Washington - Washington - United States
E-mail: contacto_rpsp@paho.org