Development and validation of a minimum requirements checklist for snakebite envenoming treatment in the Brazilian Amazonia

Background Currently, antivenoms are the only specific treatment available for snakebite envenoming. In Brazil, over 30% of patients cannot access antivenom within its critical care window. Researchers have therefore proposed decentralizing to community health centers to decrease time-to-care and improve morbidity and mortality. Currently, there is no evidence-based method to evaluate the capacity of health units for antivenom treatment, nor what the absolute minimum supplies and staff are necessary for safe and effective antivenom administration and clinical management. Methods This study utilized a modified-Delphi approach to develop and validate a checklist to evaluate the minimum requirements for health units to adequately treat snakebite envenoming in the Amazon region of Brazil. The modified-Delphi approach consisted of four rounds: 1) iterative development of preliminary checklist by expert steering committee; 2) controlled feedback on preliminary checklist via expert judge survey; 3) two-phase nominal group technique with new expert judges to resolve pending items; and 4) checklist finalization and closing criteria by expert steering committee. The measure of agreement selected for this study was percent agreement defined a priori as ≥75%. Results A valid, reliable, and feasible checklist was developed. The development process highlighted three key findings: (1) the definition of community health centers and its list of essential items by expert judges is consistent with the Brazilian Ministry of Health, WHO snakebite strategic plan, and a general snakebite capacity guideline in India (internal validity), (2) the list of essential items for antivenom administration and clinical management is feasible and aligns with the literature regarding clinical care (reliability), and (3) engagement of local experts is critical to developing and implementing an antivenom decentralization strategy (feasibility). Conclusion This study joins an international set of evidence advocating for decentralization, adding value in its definition of essential care items; identification of training needs across the care continuum; and demonstration of the validity, reliability, and feasibility provided by engaging local experts. Specific to Brazil, further added value comes in the potential use of the checklist for health unit accreditation as well as its applications to logistics and resource distribution. Future research priorities should apply this checklist to health units in the Amazon region of Brazil to determine which community health centers are or could be capable of receiving antivenom and translate this expert-driven checklist and approach to snakebite care in other settings or other diseases in low-resource settings.

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Introduction
Snakebite is considered one of the world's most serious medical problems, and the WHO recently declared snakebite envenomation a neglected tropical disease (9) and called for new strategies to combat it and resources to implement them (10).There are 5.4 million poisonous snake bites globally, fatal in around 2.5 million bites.Snake bites are accountable for 1,25,000 deaths annually. (1)WHO reported that 81-95% of snake bites occur in the tropical regions of South Asia, South-East Asia, Sub-Saharan Africa and Latin America. (2)In sub-Saharan Africa, the number of persons treated in health centers for snakebite envenomation is estimated at 315,000 cases per year, with more than 9,000 amputations and 7,000 deaths.Since many victims do not seek medical care and they are invisible to official reports thus, the actual statistics of snake envenomation remain underestimated.(8).
In some parts of the African continent, the snakebites' burden is higher than that of trypanosomiasis, leishmaniasis, and onchocerciasis, and its mortality can be higher than malaria.
The snakebites' high mortality in Africa is multifactorial, including lack of antitoxins, inadequate health care system, and scarcity of rapid access to medical centers. 3Furthermore, many inhabitants of rural areas believe in traditional healers and do not seek treatment due to low socioeconomic and health education levels and victims died shortly after the snakebite accident, and that is not reported in the hospital records.In rural regions, where most snakebite occur (8), the general population's awareness of appropriate behavior in response to snakebites is poor.A study in Nigeria showed that most patients had attempted at least one potentially deleterious first aid measure prior to presentation to hospitals. (11)In Ghana, an intervention to improve snakebite medical care ability and adherence to protocols led to a significant improvement in care and decreased significantly the snakebite mortality post the intervention. (12)  In Sudan, snakebite statistics are lacking, despite the high estimated burden of the problem. 6  During the last 70 years, only a few data were reported on the Sudanese venomous snakes.One study reported the presence of 17 medically significant snakes belonging to three major families: Burrowing asps, Elapidae, and Viperidae.These snakes usually become abundant during and after the rainy season, and most snakebite victims are farm workers. 5The records of the Natural History Museum, University of Khartoum, since the early last century, revealed some interesting data on snakes in Sudan. 5,7  To determine the poor outcome of snakebite management in Sudan, the present study was set out to determine the medical and health care providers' knowledge, attitude and practice of snakebites management.Furthermore, the study proposed that need to introduce an internet based learning management system (LMS) to support the dissemination of knowledge and practices on snakes bite management.There is proposal to use of internet based learning management system to increase awareness about snakebites due to the success of this form of internet-enabled learning in other part of Africa (23)(24)(25)(26)(27)(28).For example, South Africa used internet-mediated learning management system to tackle the issue of AIDS (24), In Libera an internet-based learning management system was introduced after the Ebola virus epidemic (23).

Material and methods
This descriptive cross-sectional survey was conducted in August 2022.It included 394 medical and health care providers from different parts of Sudan.A validated web-based selfadministrated questionnaire was used to collect the required data.The questionnaire included important and basic knowledge of snakes, snake bites and their management.A pilot study was conducted prior to the study to validate the questionnaire.The questionnaire was distributed widely online to medical and health care providers.They gave informed consent.
Sudan Snake Bite Research Network prepared this questionnaire.It contains seven different sections: section one comprised of seven socio-demographic questions on the study participants, section two had eight questions on the participants' knowledge of snakes, section three contained nine questions on knowledge of snakebites, section four contained five questions regarding practice towards snakebites, section five contained two questions regarding attitude toward snakebites, section six had seven questions regarding snakebites management and section seven included ten questions on snakebites management knowledge.

Data analysis
The data were entered into Microsoft Excel and managed by the Statistical Package for Social Sciences (SPSS) version 20 (IBM SPSSInc., Chicago, IL).Frequency and percentage were calculated for qualitative variables, and median and interquartile range (IQR) were calculated for quantitative variables.A total score of knowledge, attitude, and practice was calculated and later classified into good and poor based on the average score.Attitudes to dealing with snake bites were expressed in%. Chi-square was performed to find relationships between good knowledge, practice, and other selected variables.Questions were analyzed to determine the knowledge and practice levels.Each correct answer was given a score of 1, and the "don't know", and "wrong" answers were given 0 points.The result is expressed as%.The results were rated good and bad based on the median.

Ethical considerations
Informed oral consent from all study subjects was obtained, and confidentiality was maintained
Regarding snakebites' knowledge, there were nine questions.85 (21.6%) of the participants responded correctly to the question on handling a dead snake's head is not safe enough, 195 (49.5%) recognized the fact that marks can always be seen or found on the victim after every snake bite, 219 (55.6%) believed that a person reported at the hospital with symptoms of snakebite can be given antitoxin injection without actually being bitten by a snake, 122 (31%) believed sleeping under mosquito nets can prevent snakebites.A venomous ("poisonous") snakes always inject venom (poison) into the victim; 151 (38.3%) do not believe this statement, 316 (80.2%) recognized that the snake type determines the symptoms and signs of snakebites and 279 (70.8%) thought that the symptoms and signs of the snakebite depend on the amount of venom injected by the snake.(Table 2) 209 (53%) believed the symptoms and signs could determine the snake and venom injected, and 31 (7.9%) felt the snakebite common occurs during the day.(Table 3) For the snakebites knowledge, 179 participants (45.3%) answered the snakebite knowledge questions correctly, while 215 (54.7%) responded incorrectly.
The obtained data showed that 247 participants (26.7%) believed that a tourniquet prevents the spread of poison in the remaining part of the body, and 320 (81.2%) stated reassurance of the victim should be practice as 1st protocol for prevention.Regarding the incision at the bite site helps remove that poison, that was the belief of 186 participants (47.2%), and 282 (71.6%) thought if the leg is the bite site, its elevation will not reduce poison spread.Bringing the snake to the treating physician increases the chances of survival by correct identification of the snake believed by 297 participants (75.4%).(Table 4) In this study 37% participants get their knowledge and skill in snake bite management from their senior colleges, 28.5% self-educated and 24.3% don't know the skills.
In Kumar and et al study (14), the knowledge domain less than half i.e. (48%) of respondents had good knowledge, which is nearby to our findings 58.1% answered correctly.
100% of the study participants knew that all snakes are not poisonous as stated by Kashif Ali and et al (21).In study conducted by Kumar A and et al, majority of respondents i.e. 88 % correctly responded that all snakes are not poisonous (14), which similar to our study 81.5% respondent not all snakes are not poisonous.
In the Kumar A and et al study (14), less than half (40%) had knowledge that snake bites were fatal, which is less than our findings, more than half (64.7%) said not all snakes are venomous.
More than half i.e. (55%) agreed about the fact that snakes were important for farmers in Kumar A and et al study (14), and this is similar to our findings, 54.1% believe snakes are important for farmers, while 94% of the study participants by Kashif Ali and et al believed that snakes are helpful to farmers (21).
In Kumar a and et al study (14), majority (82%) responded correctly that deforestation and urbanization had increased human-snake interaction, which is high compared to our findings, 64.7% believed deforestation and urbanization have increased human-snake interaction.
In Kumar and et al study (14), tow third (66%) stated correctly that snakes has fangs in front of their mouth, which high compared to our findings 28.7%.
In area regarding snakebites knowledge, 45.3% participants answered the snakebite knowledge questions correctly, while 54.7% responded incorrectly.Only 21.6% participants stated handling a dead snake's head is not safe enough, which consistent to WHO guidelines, do not handle the snake with your bare hands as even a severed head can bite.(17) A venomous ("poisonous") snakes always inject venom (poison) into the victim; 38.3% do not believe this statement, 80.2% recognized that the snake type determines the symptoms and signs of snakebites and 70.8% thought that the symptoms and signs of the snakebite depend on the amount of venom injected by the snake.53% believed the symptoms and signs could determine the snake and venom injected.
Only 7.9% felt the snakebite common occurs during the day, compared to (92%) participants believed that snakes bite mostly during monsoons and at night (21).
In Kumar and et al study (14), in snakebites practice domain and after answering practice questions, only 35 % of respondent had good practice, this low compared to that found in our study, more than half (60.4%) answered snakebite practice questions correctly.
Only 26.7% in this study believed that a tight band (tourniquet) prevents the spread of poison in the remaining part of the body, when compared to study conducted in Srilanka by Anjana et al (15), application of tight band (tourniquet) proximal to the site of bite was considered as an important first aid measure among 74.9% of cases where as it was higher (96%) in a study conducted by Kumar et al. ( 16) and (89%) in Kumar A et al study (14), compared to study by Kashif Ali, all the study participants said they would tie a tourniquet at the site and would rush to the nearest health facility (21) In practice domain 89% of inters responded correctly in Kumar and et study (14) that more than half of interns i.e. (59%) responded that practice of reassurance as the first protocol in snake bite management, which is low compared to our findings 81.2% stated reassurance of the victim should be practice as first protocol for prevention.
Bringing snakes to physician in Kumar and et al study (14) , helped in correct identification of species and better patient management were recommended by more than half i.e. 54% which is low compared to our study, three quarter (75.4%).Killed snake should be taken to the dispensary or hospital with the patient in case it can be identified as stated by WHO (17).
The incision at the bite site helps remove that poison correctly answered by 47.2%, which is high and douple to that found by Kumar and et al study (14), 24%.In our findings, 28.4% from respondent correctly answered elevation of leg will reduce poison spread, which is low compared to 62% found by Kumar and et al study.(14) In attitude domain regarding snakebites attitude, Kumar and et al (14) found almost more than 8% of the interns stated right attitude, that snake bites were outcome of revenge inspired from past incidents and residing in cities is a protective factor from snake bite, which is very low compared to our findings, residing in cities is a protective factor against snakebites was stated by 75.4%, and 26.9% said that the snakebite is the outcome of revenge inspired by past incidents.
In management of snakebites, the study showed only 14% participants had rated themselves as very confident in the management of snakebites, and 51.5% participants had previously managed, supervised or nursed a snakebite patient.Regarding management and help provided by participants in snakebite management in 2021, 5.1% managed more than 100 patients, and 14.2% managed between 10 to 50 patients.40.9% stated their health facility has a protocol for managing snakebites.Only 45.4% participants said their health facility has what it takes to effectively manage snake bites.
Regarding the management of snakebites, 67.3% participants considered it an emergency.Most of the participants, 178 (45.2%) manage the snakebite by admission and treatment rather than referring patients immediately (6.6%).The patient must be transported to a place where they can receive medical care (dispensary or hospital) as quickly, but as safely and comfortably, as possible as stated by WHO (17).
As stated by WHO guidelines for the management of snakebites ( 17), 20-minute whole blood clotting test (20WBCT) is most common and very useful and informative laboratory test, in our study only sixty-one patients (15.5%) correctly said a 20-minute whole blood count test is the most appropriate test for snakebites management.
In our study 75.4% participants antivenom is the only specific antidote to snake venom, this consistent with WHO guidelines (17).50.5% participants stated antivenoms made anywhere in the world are good for the management of snake bite victims.Medical treatment is available for snakebite as stated by all participants and 86% participant knew about availability of treatment for snakebite at PHC study conducted by Kashif Ali and et al (21) Nearly half of participants (48.4%) believed that antivenoms should be given to all patients bitten by snakes, while in WHO guidelines, antivenom should be given only to patients in whom its benefits are considered likely to exceed its risks, since antivenom is relatively costly and often in limited supply, it should not be used indiscriminately.The risk of reactions should always be taken into consideration [level of evidence E]. (17) Only 14.5% thought that the intramuscular injection of an anti-snake venom is effective as an intravenous one which is consistent to WHO guidelines, intramuscular blood levels of antivenom never reach those achieved rapidly by intravenous administration (17).
Half of participants (50%) did not know how long the anti-snake venoms could remain useful after the expiry date.Anti-snake venoms can be expected to retain useful activity for months or even years after these dates if stored properly (17).Expired antivenoms could provide an alternative option for snakebite treatment (22).
In using anti-snake venoms, it is better to give low doses repeated over several days than high initial doses, 33.6% believed that is the correct regimen which is not consistent to practice.The recommended dose is often the amount of antivenom required to neutralize the average venom yield when captive snakes are milked of their venom, in practice, the choice of an initial dose of antivenom is usually empirical as stated by WHO (17).

Clinical implication of the study:
In Sudan surveillance of snakebites is essential to understand their epidemiology better and reporting of cases must be improved to provide accurate data and to facilitate stock management, training implementation, and appropriate interventions.Now that snakebites are recognized as a Neglected Tropical Disease, a global, adapted, and sustainable approach is required.Training of health care personnel represents a vital aspect of this global approach.

Technological Implication of the Study:
Due to the introduction of mobile systems in Africa and the recent development of undersea fiber optics cables, the barrier to accessing the internet-mediated knowledge management system has been dramatically reduced.The development of an internet-mediated knowledge management system that provides a repository of lessons learned and best practices with a combination of video lectures and online material (19,20) is best way to increase knowledge regarding snakes, snakebites and their Management among health workers in Sudan.

Strength and weakness of our study:
The main strength of the current study is the sample size of healthcare workers participated in the study from areas affected by snakebites (394).In addition, we have conducted a multicenter study in six hospitals from both the public and private sectors.While the limitation include, the lack of longterm evaluation of the knowledge, and exact evaluation of healthcare facilities that recipe patients affected by snakebites.

Conclusion
There is a strong need to develop an internet-mediated knowledge management system that would help in Sudan's continuing professional development process in different areas especially in snake, snakebites and management.Recent studies have shown the effectiveness and success of the learning management system (LMS) in Sudan (18).
The present study shown a gap in the knowledge on the snake, snakebite and its management, which should be addressed in different levels, personal, community and at governmental level.This area should be an important part of medical curriculum for all health professionals because they are exposed to such cases in practice.
Poor training in snake bite management, snake and snakebite knowledge, snakebite practice and lack of health facility protocols for management of snakebites management are major concerns.

Future prospects:
In order to address these issues we suggest that an intensive educational effort should be focused on basic knowledge of snakes, snakebites, prevention, management of snakebites and first aid measures.
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28. Rohwer A, Motaze NV, Rehfuess E, Young T. E-learning of evidence-based health care (EBHC) in healthcare professionals: a system atic review.Cam pbell Systematic Reviews 20 17:4, DOI: 10 .4073/ csr.20 17.4 Tables: Knowledge, Attitude and Practices of Snakes, Snakebites and their Management among Health Workers in Sudan: Need for internet-mediated Knowledge Management System for Continuing Professional Development.
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