Table 1.

Effective steps and barriers to SBE management

Region	Countrya	Manufacturer(s)	Effective steps	Barriers in SBE management	References
Asia	China	National Institute of Preventive Medicine Shanghai Serum Bio-technology Co Ltd		Haphazard ASV supply Non-specific ASVs ASV shortage	[31]
	India	Biological E Limited Premium Serums and Vaccines Pvt. Ltd VINS Bioproducts Ltd King Institute of Preventative Medicine and Research Haffkine Biopharmaceutical Corporation Ltd Bharat Serums and Vaccines Limited	Emergency ambulance service with lifesaving equipment and drugs, including ASV	Under reporting of SBE and mortality Lack of safe and effective antivenoms Poor healthcare facilities Inclination towards traditional healers ASV manufactured only against big four Untrained medical staff	[91–94]
	Indonesia	PT Bio Farma (Persero)	Antivenom cross-neutralization data required for marketing approval SBE treatment costs covered on co-payment basis	A single ASV is available Costly and limited ASV Antivenom ineffective against many Indonesian species Absence of antivenom in nearby health care facilities and lack of transportation Absence of cold-chain storage Cultural barriers	[75, 95]
	Iran	Razi Vaccine & Serum Research Institute Padra Serum Alborz	Toxicology trained physicians National unified protocol for SBE management	Under-reporting of SBE cases Preference of traditional treatment No formal clinical trial of one antivenom Antivenom starting dose not established by formal clinical trial Wound incision and fasciotomy still practiced	[74]
	Israel	Kamada limited	Short distance to hospital in some areas Uncertain snake identification in many cases	Lack of uniform treatment protocol for SBE No antivenom available against one of the venomous endemic species-Atractaspis engaddensis	[96, 97]
	Japan	KM Biologics Co. Ltd	Snake institute to help physicians	Unapproved antivenom against R. tigrinus	[98]
	Myanmar	Myanmar pharmaceutical factory	Myanmar Snakebite Project Antivenom usage reported to ministry	lack of pharmaceutical logistic system affects antivenom distribution	[75]
	Pakistan	National Institute of Health		Inclination towards traditional healers Long transportation times Manufactures liquid antivenom but has poor refrigeration facilities Low domestic supply No guidance protocol for antivenom production Inadequately trained health care workers	[99]
	Philippines	Biologicals Manufacturing Division (Research Institute for Tropical Medicine)	Subsidised antivenom production SBE treatment cost included in health insurance	Seek traditional healers ASV shortage Ineffective ASV supply chain	[75]
	Republic of Korea	KoreaVaccine Co Ltd	National reference standard for antivenom	Costly antivenoms Validated guideline for antivenoadministration unavailable No ASV against R. tigrinus	[100–102]
	Saudi Arabia	National Antivenom & Vaccine Production Center (NAVPC)	Good medical facility Antivenom available even in remote areas Established national records		[103]
	Thailand	Queen Saovabha Memorial Institute	Well-established supply chain real-time antivenom inventory	No national training on SBE management since 2016	[75]
	Vietnam	Institute of Vaccines and Biological Substances (IVAC)		Inclination towards traditional practices Poor documentation of SBE records Lack of SBE statistics Limited studies on clinical presentation of SBE No national protocol for SBE management Antivenom shortage and high cost Long distance to hospitals Lack of trained HCPs Lack of SBE education and public awareness Monovalent antivenoms prevalent which require accurate snake identification Use of antivenoms of unknown efficacy and potency Only one study on adverse reaction to antivenom so far	[68]
Africa	South Africa	South African VaccinProducers (SAVP)	Free toxicology advice to HCPs and public at all hours Trained physicians Free snake identification charts	Discrepancy in antivenom availability in urban and rural areas SBE reporting not mandatory Need of cold chain transport Short expiry of ASVs	[39, 104]
	Tunisia	Institut Pasteur de Tunis		No validated scale of SBE severity Limited studies on SBE Lack of health facilities in rural areas Delay between bite and hospital arrival Propensity for at home first aid such as tourniquets	[105]
North America	Costa Rica	Instituto Clodomiro Picado	Free antivenom SBE notification mandatory Traditional medicine rarely used Quality control of antivenoms Good cold chain National protocol for SBE diagnosis and treatment Regular training sessions on SBE management	A part of population is devoid of SBE related governmental aids, such as agricultural workers Access to health facility delayed in some regions	[106]
	Mexico	Birmex (Instituto Nacional de Higiene) Laboratorios Silanes, S. A. de C. V		Inclination towards traditional healers Limited data on SBE epidemiology	[107]
	United States	BTG International Inc Wyeth (owned by Pfizer)		Cost transparency Concerns about insurance cover Antivenom not available at all facilities Costly antivenom Controversial maintenance therapy	[108, 109]
South America	Bolivia	Ministerio de Salud y Deportes, Instituto Nacional de Laboratorios De Salud		Snake misidentification Untrained HCPs	[110]
	Brazil	Fundacao Ezequiel Dias (FUNED) Centro de Producao e Pesquisas de Immunobiol Instituto Butantan Instituto Vital Brazil S.A	Compulsory case notification Free antivenom	Inclination towards traditional practices No antivenom in rural areas Lack of trust in local health care Low confidence among clinicians in SBE management Overdosing and under-dosing of antivenoms Antivenom expiration owing to lack of inventory Antivenom storage issues due to lack of stable electricity Limited ASV production capacity	[64, 111]
	Colombia	Instituto Nacional de Salud (CO) Laboratorios Biologicos PROBIOL Ltda	Mandatory reporting	Regular antivenom shortage Lack of cold chain transport No policy for antivenom distribution	[63]
	Ecuador	Instituto Nacional de Higiene y Medicina Tropical "Leopoldo Izquieta Pérez"	Fixed maximum price for antivenom	Antivenom production stopped in 2012 Dependent on import of ASV from Costa Rica	[24]
Europe	Croatia	Imunološki Zavod (Institute of Immunology)	Low reported mortality	Last antivenom batch expired in 2019 Dependent on imports now	[25]
	Serbia	Institute of Virology, Vaccine and Sera TORLAK	Antivenom available Snakes protected by law	HCPs unawareness of species in their areas Snake misidentification common	[85]
	Spain	INOSAN BIOPHARMA S. A. (Spain)	Very few cases and fatalities		[112]
	The United Kingdom	Micropharm Ltd	24 h rapid clinical advice available through poison centres	Exotic snakebites a challenge	[113]
Australia	Australia	Seqirus Pty Ltd		Costly ASV Need of cold chain transport Limited shelf-life Single antivenom to treat envenoming by all sea snakes – due to rarity of sea snake envenoming-more time for administering antivenom than terrestrial SBE cases Limited clinical evidence to support use of this antivenom for sea snake envenoming	[21]

The table lists the anti-snake venom (ASV) manufacturing countries and companies. Additionally, it presents a non-exhaustive list of effective steps taken by ASV manufacturing countries and the existing gaps in snakebite management. The information has been sourced from the WHO snake ASV database [23] and the most recent literature (2020-present) to provide insights into the present situations in these countries. The list is by no means exhaustive and additional steps or gaps might be present in the respective countries

^aFor Algeria, Argentina, Bulgaria, Egypt, Peru, Poland, Russia, Turkey, Uzbekistan, and Venezuela, no relevant literature, published 2020 onwards, could be found