Use of prospective clinical, epidemiological, phylogenetic and other studies to improve the management of snakebite in a developing country setting

Research Questions

This project examines the key question of how the burden from snakebite can be dealt with most effectively and efficiently by developing nations, such as Papua New Guinea.

In order to answer this question it is essential that a fundamental understanding of the state of health infrastructure and administration, and its capacity to make dynamic responses to health issues be sought out. To obtain this measure of systems performance the research needs to explore not just the clinical fundamentals of snakebite, but also the larger health service framework within which the problem must be addressed.

In the case of Papua New Guinea a fractured and largely ineffectual health service is as much to blame for high morbidity and mortality as are problems experienced in the individual clinical management of each snakebite emergency. Resolving the question of how to deal with the high human and financial costs of the problem necessitates a broad approach encompassing epidemiological, clinical, zoological, toxinological and public health management research. The projects undertaken during this candidature for Doctor of Philosophy seek to accumulate the answers to individual questions that will cumulatively provide practical and sustainable solutions to the broader issues that apply not just in Papua New Guinea, but in many other of the world’s tropical developing nations.


 

Specifically this project seeks to resolve a number of questions:

  1. How best can quantitative measures of injury burden, such as crude incidence and mortality at regional, provincial and national levels be reliably measured, and what systems can be established to facilitate surveillance and dynamic monitoring within the health infrastructure?
  2. Who are the culprits? Which species of venomous snakes are responsible for injury in particular regions of the country? What relationships exist between populations and are all populations homogenous, or do significant variations in phylogeny translate to significant variations in venom composition and clinical syndromes?
  3. What are the clinical syndromes of envenomation at species level? How are these conditions managed? What sustainable improvements to the clinical care of patients and to the operations of service delivery systems can be made that will produce tangible benefits in the form of reduced morbidity and mortality at all levels of the system?
  4. Can public education and first aid training be effective tools for reducing the incidence of snakebite, and for improving the prognosis of the snake-bitten? Can the techniques of snakebite first aid be successfully taught to those in most need of these skills, and what is the efficacy of the training approach?
  5. Does ongoing professional training, education and access to information functionally improve the skills of the medical and paramedical workforce? Can we measure tangible improvements in the outcomes for envenomed patients over time? Does a structured program of training combined with standardisation of treatment protocols and procedures translate into real improvement in patient prognosis?
  6. Can we develop a model system in Papua New Guinea for the successful sustainable management of resources such as antivenoms? Can the rising costs of treatment be curtailed by a coordinated national approach and the establishment of local research and clinical capacity? Can new avenues for reducing cost and maintaining the supply of antivenoms be established within nations such as Papua New Guinea, and can a successful international model be established through cooperation with more affluent neighbours or through strategic regional alliances?
  7. Can all of these approaches, collectively, be maintained, and can lives be saved?

Summary and analysis of relevant literature

Note: A comprehensive literature review has been published previously1 and can be found here

Although a number of detailed studies of snakebite have been conducted in Papua New Guinea2-5, there has been no diminution of the burden that these encounters between humans and reptiles produce1. Snakebite remains a common cause of injury and death, especially for young, rural-dwelling people in southern Papua New Guinea1. Analysis of mortality data at Port Moresby General Hospital6 suggests that the treatment and management of snakebite patients was not improved by previous clinical research conducted more than a decade ago4-5. Looking further back to the earliest studies of snakebite in PNG conducted by Dr C H Campbell in the 1960’s2, it appears that the prognosis for patients has actually declined, rather than improved1.

Campbell reported a case fatality rate of 6.8% after snakebite at Port Moresby General Hospital (PMGH) during the years 1959 to 19652, and Price & Campbell gave a mortality rate of 3.1% among 192 patients admitted to the hospital between January 1967 and December 19717. In the 1980’s the case fatality rate among children at PMGH was 7.7%3, but a study soon afterwards found that while the overall case fatality rate between 1987 and 1992 was 4.4%, the rate among children was actually 10.0% compared to an adult rate was 3.3%5.

Case fatality rates after snakebite at PMGH have continued to increase since the early 1990’s. A study of snakebite deaths in the Intensive Care Unit (ICU) between 1992 and 2001 by McGain et al found that 87 of 722 patients died (12.0%), with rates of 14.6% for children and 8.2% for adults6. Williams et al studied ICU cases between 1998 and 2001 and found that 13.5% of female snakebite patients died compared to only 7.7% of men8. More recently a 12 month review of snakebite cases admitted to the ICU at PMGH between September 2003 and August 2004 found an adult case fatality rate of 14.5% and a paediatric case fatality rate of 25.9% (Unpublished data: current study).

This apparent increase in mortality rates is an important focus of the research being undertaken in the current study. Little is known of the determinants of mortality outside the findings reported by McGain and colleagues as part of their retrospective analysis of PMGH ICU admissions. By nature of the design of their study, the data is limited to medical causes of death, and provides no information on extraneous factors such as hospital systems failures. A prospective study is being undertaken as part of this PhD research that seeks to explore both the clinical and non-clinical contributors to mortality and/or prolonged morbidity.

Current understanding of the syndromes of envenomation produced by particular species has been well described by the student in a recent publication1. The effects of bites by one species, the Papuan taipan Oxyuranus scutellatus canni are well described9-12, although an understanding of the mechanisms of some observed effects is not yet available. Suspicion that venom from this species causes direct myocardial toxicity has been suggested based on observed electrophysiological changes10, but direct evidence of myocardial damage has not been presented. A prospective study of troponin-I levels in patients with definite O. s. canni envenoming is being undertaken now in an attempt to obtain quantitative evidence of myocardial damage after bites by this snake.

Descriptions of the effects of envenomation by other medically important species in PNG are limited to a handful of small patient series13-16. Prospective recruitment of patients with ELISA-proven envenoming by Papuan blacksnakes Pseudechis papuanus, death adders Acanthophis spp., and small-eyed snakes Micropechis ikaheka to a study of haemostatic and biochemical changes will significantly improve our understanding of the individual syndromes of envenoming produced by these taxa.

Conceptual framework

The research being undertaken in PNG by David Williams seeks to resolve a number of the outstanding issues relating to not just the treatment of snakebite patients, but also addresses the broader topics of surveillance and reporting, resource allocation, public health education, workforce training and fundamental scientific research.

Broadly speaking, the overall project is a conglomeration of several smaller inter-related research activities being conducted in various locations in Papua New Guinea. These individual projects can be grouped as:

This approach therefore aims to:

The research is taking place in Papua New Guinea, at various locations in close consultation with the PNG National Department of Health who are David Williams' sponsors, and with both local administrators and clinicians. The individual projects that comprise the research are listed below. Projects involving human or animal research have been approved by either the PNG Medical Research Advisory Committee, or the University of Papua New Guinea Medical Ethics Committee.

How you can help us save lives in Papua New Guinea

 

None of the work we are currently doing is supported by any formal funding, but with basic annual project costs of more than A$150,000.00 we are facing an uphill struggle to maintain our current impetus, and the launch of new projects, such as our plan to hire local health workers to teach the life-saving pressure-immobilisation bandaging technique of first aid to 25,000 families across rural Central Province, is having to be moth-balled until such time as funding support can be secured.

So how can people help this effort to reduce snakebite mortality in PNG?

There are several ways in which people can help:

Donations of crepe, elastic bandages

To get our snakebite first aid project off the ground we need 50,000 crepe, elastic bandages (i.e., Handy crepe 15 cm elastic bandages) to distribute with the first aid materials already donated to us by CSL Limited. If you happen to be an executive at Smith & Nephew or Beiersdorf and are willing to consider donating the whole lot - I would absolutely love to hear from you, but donations of even a few bandages from the household medicine cupboard, will be just as warmly accepted. Every two bandages we get means another family we can teach to help themselves in an emergency...

Donations of equipment

We would welcome the opportunity to help hospitals, community groups and medical supply houses provide donations of basic and other medical equipment to facilities in PNG. Much of the basic equipment needed to treat snakebite (and other) patients is in short supply, and we are currently eager to obtain second-hand monitoring equipment, resuscitation gear, laryngoscopes, airway devices and ventilators to improve the capacity of Port Moresby General Hospital and other health facilities around the country.

Cash Donations

We really do need money desperately. Much of our work lies outside the normal academic-orientated criteria of traditional grant making organisations like the Australian Research Council and the National Health & Medical Research Council. They just don't fund applied research, education and training such as this.

The good news is that donations to the Australian Venom Research Unit are administered by financial boffins at the University of Melbourne who apply very exacting and strict financial reporting controls. That means every dollar donated gets used for the purpose it was donated for, without exception. If you donate money to AVRU for our work in PNG, that is exactly where your money will go.

And yes it is tax-deductible.

Donations to the Australian Venom Research Unit will help us save lives in PNG, so if you can spare even a few dollars, please do so.

Donations to the PNG Snakebite Research Project

Please forward donations to:

Australian Venom Research Unit
Department of Pharmacology, University of Melbourne
Cnr Grattan Street & Royal Parade
Parkville, Vic, 3010. Australia.

Contact: Dr Ken Winkel (+61 3 8344 7753) or David Williams (+675 684 7748)

Bibliography

  1. Williams DJ, Jensen SD, Nimorakiotakis B, Winkel KD (Eds). Venomous Bites and Stings in Papua New Guinea: A Treatment Guide for Health Workers and Doctors. Australian Venom Research Unit, Melbourne, September 2005, 416 pp. ISBN 0-975937-0-5.
  2. Campbell CH. A clinical study of venomous snakebite in Papua. MD thesis, 1969, University of Sydney.
  3. Brian MJ, Vince JD. Treatment and outcome of venomous snake bite in children, Port Moresby General Hospital, Papua New Guinea. Trans R Soc Trop Med Hyg 1987; 81: 850-2.
  4. Currie BJ, Sutherland SK, Hudson BJ, Smith AM. An epidemiological study of snakebite envenomation in Papua New Guinea. Med J Aust 1991; 154: 266-268.
  5. Lalloo DG, Trevett AJ, Saweri A, et al. The epidemiology of snakebite in Central Province and National Capital District, Papua New Guinea. Trans Roy Soc Trop Med Hyg 1995; 89:178-182.
  6. McGain F, Limbo A, Williams DJ, et al. Severe Snakebite at Port Moresby General Hospital, Papua New Guinea 1992-2001. Med J Aust 2004; 181: 687-691.
  7. Price M, Campbell CH (1979) Snake bite admissions PMGH 1967-1971. PNG Med J; 19: 155
  8. Williams DJ, Kevau IH, Hiawalyer GW, et al Analysis of Intensive Care Unit admissions for treatment of serious snakebite at Port Moresby General Hospital. Proceedings of the 11th Annual Scientific Meeting of the Australasian College of Tropical Medicine and the 6th Asia-Pacific Congress of the International Society of Toxinologists .Cairns, Australia (July 8-12, 2002).
  9. Lalloo DG, Hutton R, Black J, et al. (1993) Mechanisms of coagulopathy following envenoming by the Papua New Guinean Taipan. Toxicon. 31(8):937
  10. Lalloo DG, Trevett AJ, Nwokolo N, et al. (1997) Electrocardiographic abnormalities in patients bitten by taipans (Oxyuranus scutellatus canni) and other elapid snakes in Papua New Guinea Trans Roy Soc Trop Med Hyg. 91(1):53-6.
  11. Lalloo DG, Trevett AJ, Kornihona A, et al. (1995a) Snake bites by the Papuan taipan (Oxyuranus scutellatus canni): Paralysis, hemostatic and electrocardiographic abnormalities, and effects of antivenom. Am J Trop Med & Hyg. 52(6): 525-31.
  12. Trevett AJ, Lalloo DG, Nwokolo NC, et al. (1995b) The efficacy of antivenom in the treatment of bites by the Papuan taipan (Oxyuranus scutellatus canni) Trans Roy Soc Trop Med Hyg. 89:322-25.
  13. Campbell CH. (1966) The death adder (Acanthophis antarcticus): the effect of the bite and its treatment. Med J Aust. 2:922-925
  14. Lalloo DG, Trevett AJ, Black J, et al. (1996) Neurotoxicity anticoagulant activity and evidence of rhabdomyolysis in patients bitten by death adders (Acanthophis sp.) in southern Papua New Guinea. Q J Med. 89:25-35.
  15. Lalloo DG., Trevett A, Black J, et al. (1994) Neurotoxicity and haemostatic disturbances in patient's envenomed by the Papuan black snake (Pseudechis papuanus). Toxicon. 12(8):927-936.
  16. Warrell DA, Hudson BJ, Lalloo DG, et al. (1996) The emerging syndrome of envenoming by the New Guinea small-eyed snake Micropechis ikaheka. Q J Med. 89:523-30.

 

Last updated: February 2007