eMJA: Cheng & Winkel, Snakebite and antivenoms in the Asia-Pacific: wokabaut wantaim, raka hebou ("walking together")

eMJA The Medical Journal of Australia

Bites and stings

Snakebite and antivenoms in the Asia-Pacific: wokabaut wantaim, raka hebou ("walking together")

Although responsibility for health is national, the means to fulfil that responsibility are increasingly global.

Allen C Cheng and Kenneth D Winkel

MJA 2001; 175: 648-651

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3 AM. The phone falls to the floor as I grope around in the dark.
"We have another one for you, boss", the voice says, with the schadenfreude that the night doctors feel when summoning the on-call staff.
"What, another snakebite ?" I wonder what the poor man was doing getting bitten at that hour.
It has been a tough night for the emergency doctors. Patients look up hopefully at the first sign of a doctor, while others complain to triage. There is some blood on the floor in the main room; the smell of sweat hangs thick in the air.
The interns gesture tiredly in the direction of the resuscitation room. "There is a transfer letter somewhere," they tell me. It is a pithy statement of fact, even for Papua New Guinea. "Thank you for taking K, who is 12 years old. He was bitten by a snake at 6 PM. We have no tet tox or penicillin. We have no antivenom. Yours truly." I'm not sure if they mean to tell me that they have thought of these things, or they are hoping we will provide some for them.

Although Australian snakebite mortality rates have fallen more than tenfold since the introduction of the first antivenom 70 years ago¹ (see Box 1), our nearest neighbour, Papua New Guinea (PNG), has not been so fortunate. Not only do they share with us snakes that are among the most toxic known, but in some areas the snakebite rate is one of the highest in the world.² Moreover, the consequences of snakebite in PNG are particularly severe; 36% of envenomed patients seen at Port Moresby General Hospital (PMGH) will require ventilation³ (see Box 2). In an ironic twist, Gajdusek, whose work on kuru among the Fore people underlies contemporary understanding of "mad cow disease" (which has received much funding and international attention), also reported that snakebite was the commonest cause of death in some of these villages.⁴ At the same time, the cost of a single ampoule of Australian polyvalent antivenom (CSL Limited), the type most frequently used in PNG,⁵ at over A$1200, represents approximately half the per capita annual gross domestic product (Anna Leina, Officer in Charge, Pharmacy Department, Port Moresby General Hospital, personal communication). Consequently, even the nation's premier medical institution, Port Moresby General Hospital (PMGH), is frequently without antivenom.⁶ This situation, unthinkable in Australia, has forced some healthcare centres into managing death adder bites with prolonged pressure bandaging to save scarce antivenom supplies.⁷

The child is not well. Held up by his tired parents, his eyes are heavy from fatigue and from the neurotoxin that is taking over. He is still breathing, with some effort. He does not care that saliva spills from his chin onto his T-shirt. He will need to be ventilated soon, but not yet. His blood does not clot. I have learned not to ask the lab to tell me how long it takes; once I called for missing results only to be told that they couldn't give me a clotting time, as they were still waiting. It has been a steep learning curve for me.
The refrigerator in the emergency department has contained two ampoules of sea snake antivenom for a few years now. No-one at the hospital has ever heard of anyone being bitten by a sea snake. The paediatric ward staff tell me they do not have any polyvalent antivenom, but I run across to make sure. It would not be the first time they have tried to save some antivenom. Pharmacy is locked, but I checked there earlier in the day. The nurses in intensive care eye me suspiciously. "We are full, boss."

It has been just over a hundred years since Calmette successfully developed the first antivenom, using cobra venom from Indo-China, now Vietnam.⁸

Unfortunately, little has changed regarding antivenom availability for snakebite victims in this region during the past century. The global burden of this eminently treatable condition is estimated at approximately 100 000 deaths each year,⁹ about a tenth the mortality attributable to malaria. Most of these deaths are concentrated in the Indo-Pacific region,¹⁰ where the poor (or absent) access to antivenom for most people results in snakebite mortality orders of magnitude greater than that in Australia (see Box 3). Indeed, tragically, although the burden of snakebite on the local people stimulated Calmette's original studies at the Vaccine Institute in Saigon (now Ho Chi Minh City),¹¹ no snake antivenom was made in Vietnam for the next 100 years.

There were five snakebites today and two yesterday — unusual even here. There are over 100 snakebite victims seen each year at Port Moresby General Hospital and we had received 20 ampoules of antivenom in the year 2000. There are seven ventilators. I try again to wrest an ampoule of antivenom from the intensive care ward by telling the staff that this patient might not need to come up to their ward if he had some. They honestly do not have any.
I try all the tricks. Neostigmine sometimes helps if the snake was a death adder. I know that over 90% of bites are from taipans, but it is worth a try. I wonder if the scientists who theorised about cholinergic neurotoxins ever thought that it would come to this. It has been said that as the horses used to produce antivenoms for other snake venoms were the same ones used for the taipan antivenom, the antivenoms might have some activity against other snakes. Perhaps the sea snake antivenom might yet be useful. . .

We recently proposed a global strategy for snakebite control and procurement of funding to overcome the inequality of antivenom supply.¹² This comes amid an acute crisis in antivenom availability for Africa¹³ and a long-standing undersupply in the Asia-Pacific region^14-16 (see Box 3). Echoing Nossal's call to awaken the global conscience to the resource constraints facing childhood vaccination,¹⁷ we note that the greatest barrier to the widespread availability of antivenoms is not technical, but rather the mobilisation of enough resources.

Fortunately for childhood vaccination, the establishment of the Global Fund for Childhood Vaccines by the William H Gates Foundation represents an unprecedented opportunity for infectious disease control by a systematic change in vaccine procurement methods.¹⁸ This change recognises that while "responsibility for health is national . . . the determinants of health and the means to fulfil that responsibility are increasingly global".^18,19 A similarly coordinated international strategy is required to tackle the neglected issue of snakebite.

We propose a comprehensive program that builds on the resources and relationships acquired by the Children's Vaccine Initiative²⁰ and on World Health Organization (WHO) policy initiatives towards securing global access to essential drugs.²¹ It would employ strategies such as that adopted by the Pan American Health Organization's revolving fund, which emphasises sustainability by long-term government commitment before donor-supported expansion.²² This International Snakebite Initiative (ISI) would recognise that antivenoms are, like vaccines, international public commodities usually manufactured by the same companies facing the same pressures of economics.¹⁸ This is already recognised implicitly by the inclusion of antivenoms in the WHO's essential drug list.²³ The ISI would require an interdisciplinary and multisectoral partnership maintaining national responsibility and aiming, where possible, for antivenom self-sufficiency. In addition to procurement, it would facilitate the development of new antivenom technology and adjuvant therapies. It would also encourage sustained primary-prevention programs, sponsor research and implement appropriate first-aid methods, ongoing snakebite injury surveillance and improved clinical education tools such as regional snakebite management guidelines.

I intubate the boy, leave the intern with the bag, and go back to intensive care and give the staff the bad news. They tell me again that there are no ventilators. I ask which patients' wantoks (relatives) are staying with them. I tell them that we need the ventilator for a child and that they will have to help.
I disconnect a patient's ventilator and attach the bag to his tube, explaining to his relatives,"This is how you breathe for him. If you stop, he does not breathe." The lesson is easily understood. We transfer the boy from emergency to intensive care and the other patients' relatives look at us impassively.

As highlighted by the reduction in Australian snakebite mortality over the past century, dedicated venom and antivenom research and production saves lives and alleviates suffering. Unfortunately, the global tendency to privatise government-owned antivenom manufacturers,^13,24 unleashing free market forces in countries with poor pharmaceutical regulation, threatens the humanitarian task of international snakebite control.^13,14,16,25 For example, fake antivenoms are widely sold in Nigeria, and in many countries only charlatans or traditional healers are available to manage snakebite.^13,14 These difficulties, combined with the cessation or reduction in antivenom production by traditional manufacturers, such as Aventis Pasteur, have precipitated escalating snakebite mortality in Africa.¹³

Locally, efforts to enhance antivenom availability in PNG through calls for direct or indirect price subsidies^16,25 have been ineffective.^12,16,25,26 This reflects the general difficulty of facilitating access to essential drugs by appeals to charity or corporate social responsibility.²¹ Commercial disinterest in this class of pharmaceuticals is clearly evident in the apparent recent withdrawal of the incumbent snake antivenom manufacturer from the United States market.²⁷ This has handed a monopoly to the new producer, which is now selling the most expensive antivenom in the world.¹⁴ We therefore argue that a new and more sustainable approach to antivenom procurement is required. Our proposal places antivenoms within global initiatives to secure access to essential drugs, particularly immunotherapeutics, in partnership with donors, the public sector and the pharmaceutical industry.²¹

Despite these challenges there is room for optimism. The chosen theme of PNG's 25th anniversary of Independence last September was "Walking together", or Raka hebou in Motu and Wokabaut wantaim in Tok Pigin. This theme resonates strongly with our aspirations for regional and global partnerships for snakebite control. Australia, with its distinguished record in antivenom research and development as well as in the Children's Vaccine Initiative, has the potential to play a leading role in the ISI. Countries with a high burden of snakebite, such as PNG and Vietnam, have well-organised national health systems effectively participating in global vaccination programs and disease eradication.²⁸ Australian medical staff assist with snakebite management in regular regional toxinology teaching workshops and courses,²⁹ and by international hospital-based, exchanges, sponsored by Australian institutions.³⁰ Indeed, in the very week of PNG's Silver Jubilee celebrations, two such snakebite workshops were held at PMGH by one of us (K D W).

Nevertheless, the need for global snakebite control is urgent and "action plans express no outrage".³¹ Unless affluent nations like Australia rise to this challenge, variations on our tragic scene will be replayed daily throughout the Asia-Pacific region for want of a 19th-century therapy.

Acknowledgements

We thank Professor Emeritus Sir Gustav Nossal, Professor Graham Brown and Dr Gabrielle Hawdon of the University of Melbourne, Dr Gertrude Didei of the Port Moresby General Hospital, Dr John Reeder of the Papua New Guinea Institute of Medical Research, and Professor David Warrell, University of Oxford, for their critical review of the manuscript. We are grateful to Dr Forbes McGain for the use of his photograph. Thanks also to CSL Limited and Boucher and Muir for sponsoring K W's trip to Port Moresby and to the ongoing Medical Officer, Nursing and Allied Health Training Project, for its support of A C's part in the registrar exchange program with PMGH. We acknowledge the continuing support of the Victorian Department of Human Services for the work of the Australian Venom Research Unit.

Competing interests

None declared. The preparation of this article received no specific funding from any organisation.

References

Winkel KD. Strychine, ammonia and gunpowder for snake bite — the end of an era. Med J Aust 2001; 174: 607.
Lalloo DG, Trevett AJ, Saweri A, et al. The epidemiology of snake bite in the Central Province and National Capital District, Papua New Guinea. Trans R Soc Trop Med Hyg 1995; 89: 178-182.
Warrell DA, Lalloo DG. Snake bite and its treatment in Papua New Guinea. In: O'Shea M, editor. A guide to the snakes of Papua New Guinea. Madang, Papua New Guinea: Christensen Research Institute, 1996.
Gajdusek DC. Urgent opportunistic observations: the study of changing, transient and disappearing phenomena of interest in disrupted primitive human communities. In: Ciba Foundation Symposium 49 (new series), editors. Health and diseases in tribal societies. Amsterdam: Elsevier, 1977.
Trevett AJ, Lalloo DG, Nwokolo NC, et al. Venom detection kits in the management of snakebite in Central Province, Papua New Guinea. Toxicon 1995; 33: 703-705.
Dyke T. In the tail of the taipan. A personal view of snakebite and serum sickness. Med J Aust 1995; 163: 614-615.
Oakley J. Managing death adder bite with prolonged pressure bandaging. In: Handbook, Millennium 2000, the 36th PNG Medical Society Symposium. Port Moresby, Papua New Guinea: PNG Medical Society, 2000: 24.
Calmette A. Propriétés du sérum des animaux immunisés contre le venin des serpents; thérapeutique de l'envenimation. C r hebd Seanc Acad Sci Paris 1894; 118: 720-722.
Chippaux J-P. Snake bites: appraisal of the global situation. Bull World Health Organ 1998; 76: 515-524.
WHO/SEARO guidelines for the clinical management of snake bites in the Southeast Asian region. Southeast Asian J Trop Med Public Health 1999; 30 (Suppl 1): 1-85.
Calmette A. étude éxperimentale du venin de Naja tripudians or cobra capel. Ann l'Institute Pasteur 1892; 6: 160-183.
Cheng AC, Winkel KD. Call for global snakebite control and procurement funding [letter]. Lancet 2001; 357:1132.
Theakston RD, Warrell DA. Crisis in snake antivenom supply for Africa [letter]. Lancet 2000; 356: 2104.
McNamee D. Tackling venomous snake bites worldwide [news]. Lancet 2001; 357: 1680.
Currie B, Vince J, Naraqi S. Snake bite in Papua New Guinea. PNG Med J 1988; 31: 195-198.
Currie B. Medicine in tropical Australia: the quality and price of snake antivenoms [letter]. Med J Aust 1993; 159: 284.
Nossal GJV. Awakening the global conscience: Who will benefit from new vaccines in the 21st century? Immunol Cell Biol 1997; 75: 584-586.
Mahoney RT, Ramachandran S, Xu Z-Y. The introduction of new vaccines into developing countries II. Vaccine financing. Vaccine 2000; 18: 2625-2635.
Jamison DT, Frenk J, Knaul F. International collective action in health: objectives, functions and rationale. Lancet 1998; 351: 514-517.
Muraskin WA. The politics of international health. Albany: State University of New York, 1998.
Scholtz M. WHO's role in ensuring access to essential drugs. WHO Drug Infor 1999; 13: 217-220.
Freeman P. The PAHO revolving fund: history, operations and contribution to speeding vaccine introductions. Geneva: Children's Vaccine Initiative, 1999.
Essential drugs: WHO Model list, 11th revision. WHO Drug Infor 1999; 13: 245-258.
Sutherland SK. The sale of Commonwealth Serum Laboratories: wither antivenom research? Med J Aust 1992; 157: 731-732.
Cheng AC, Ratcliff A, Adhikari P. Snake anti-venom in Papua New Guinea. Fellowship Affairs 2000; 19: 26.
Sutherland SK. Medicine in tropical Australia: the quality and price of snake antivenoms. Med J Aust 1993; 159: 284.
Galli R. The antivenin is safe, but its future is uncertain. West J Med 2001; 175: 91-92.
Temu P. Health Secretary's message to the 2000 medical symposium. In: Handbook, Millennium 2000, the 36th PNG Medical Society Symposium. Port Moresby, Papua New Guinea: PNG Medical Society, 2000: 6-9.
White J, editor. Clinical toxinology short course. 2001 handbook. Adelaide: University of Adelaide Faculty of Health Sciences, 2001.
AusAID. Papua New Guinea program profiles, 1999-2000. Canberra: Australian Agency for International Development, 2001.
Einternz EM. International aid and medical practice in the less-developed world: doing it right. Lancet 2001; 357: 1524-1525.

(Received 19 Jul, accepted 1 Nov, 2001)

Authors' details

Duke University Medical Center, Durham, NC, USA.
Allen C Cheng, MB BS, Fellow in Infectious Diseases.

Department of Pharmacology, University of Melbourne, VIC.
Kenneth D Winkel, MB BS, PhD, Director, Australian Venom Research Unit.

Reprints: Dr K D Winkel, AVRU, Department of Pharmacology, University of Melbourne, VIC 3010.
kdwATunimelb.edu.au

Acknowledgements

Competing interests

References

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