Enrique Chaves-Carballo
Kansas City, Kansas, United States

Rikki-tikki had a right to be proud of himself. But he did not grow too proud, and he kept that garden as a mongoose should keep it, with tooth and jump and spring and bite, till never a cobra dared show its head inside the walls.
—Rudyard Kipling, “Rikki-Tikki-Tavi,” The Jungle Book

Tropical nights are usually marked by a reassuring cacophony of sounds from insects, frogs, and birds. As I settled in for a weekend on call in the emergency room at a small hospital in the Panama Canal Zone, however, there was a stillness in the air that made me uneasy as to what the rest of the night would bring. My foreboding thoughts were soon broken by an ambulance siren signaling the arrival of my first patient. The excited orderlies carried a young girl into the emergency room on a gurney and yelled, “Snake bite! Snake bite!”

My heart sank as I felt the despondency of ignorance, having attended medical school and pediatric residency training in the United States without ever hearing or reading anything about snake bites. My initial evaluation indicated this ten-year-old Panamanian girl had stepped out of her home in a nearby village and a pit viper, locally called fer-de-lance (Bothrops lanceolatus), had bitten her left foot, which was now swollen, and the two fang marks were oozing blood freely. She was unresponsive except to deep pain, and her gums were bleeding profusely. That empty-stomach feeling returned as I called the main hospital only to find out that the only local snake bite expert was on vacation. An immense weight fell on my shoulders as I realized this young girl’s life, which was fading rapidly in front of my eyes, was my responsibility. The nurse nudged me into reality as she calmly told me that the antiserum was in the pharmacy in the basement of the hospital. I found eight ampules from the Institute Butantan in Brazil in the refrigerator and took five of them, not knowing what dose was recommended for a child. Thinking it was better to err on the side of too much than too little, I gave the patient all five vials. Thirty minutes later, the girl became more responsive and stopped oozing blood from her mucous membranes and wounds. Next morning, I found her happily eating breakfast surrounded by a grateful family. Although I am not a religious person, I almost felt like crying for the help I received in making the right decisions in this case. A week later, the girl was transferred to the main hospital for a fasciotomy of her foot to improve circulation, which was compromised by the swelling. A month later, I saw her in my clinic accompanied by her parents, who brought a precious pineapple as gift to me for saving their daughter’s life.

Although survival in this case may appear to have been serendipitous, it serves to illustrate several important points about snake bite treatment. Survival depends on rapid and effective administration of antiserum, as well as critical supportive care. The correct dose of antivenom should not be based on weight of the victim but on careful monitoring of swelling, bleeding, and level of consciousness. The venom is more concentrated in a child and may require larger doses than anticipated. A typical initial dose is two vials, but may require as many as five vials titrated until the patient is stable. Prompt treatment is crucial, as the envenomation may be irreversible after thirty minutes. Fortunately, in the case described, the village was only ten minutes away by ambulance from the hospital. A sufficient supply of antivenom proven to be safe and effective must be readily available.

Local manifestations of snake envenomation are pain and swelling at or near the portal of entry emerging within thirty to sixty minutes after a bite. Systemic manifestations usually consist of nausea, vomiting, paresthesia, lethargy, and weakness. These may progress rapidly to hypotension, respiratory distress, tachycardia, and impaired consciousness. A consumptive coagulopathy results in oozing blood from punctured skin and mucous membranes, as well as laboratory abnormalities in prothrombin time, partial thromboplastin time, hypofibrinogenemia, fibrin-degradation products, and low platelet counts.

Earlier studies attempted to explain the pathophysiology of snake venom based on the simple assumption of two toxic components—a neurotoxin and a hematotoxin—to explain the known respective adverse effects of envenomation.¹ However, molecular studies have revealed a more complex composition of toxins affecting multiple binding sites, giving birth to the relatively new field of proteomics, which promises not only a better understanding of envenomation but the possibility of medicinal applications for these poisons.² Metalloproteinases, serine proteases, and C-type lentils have anticoagulant or procoagulant activity, while phospholipase A and three-finger proteins inhibit pre-synaptic or post-synaptic transmission by affecting acetylcholine receptors.

The World Health Organization in 2018 declared snake envenomation one of the world’s neglected tropical diseases.³ In the United States, approximately 7,000 to 8,000 bites from venomous snakes occur per year, with five to six deaths. Global totals are 5,400,000 bites and 125,000 deaths per year. However, an estimated 2.7 million persons suffer snake bites worldwide, resulting in 400,000 amputations or permanent disability. In sub-Saharan Africa, 7,000 to 20,000 deaths occur each year from snake envenomation. Unfortunately, the poorest countries possess the greatest toll due to lack of accessible hospital facilities and high cost of antivenom serum. In Ghana, serum is imported from Costa Rica, but the price is increased by intermediaries, and patients or their families must bring the serum to the hospital at a cost of $100 per vial. An initial dose requires two vials at a prohibitive cost of $200, beyond the reach of most victims.

The non-profit organization Médicins sans Frontiéres (Doctors without Borders; MSF) has admitted more than 3,000 patients to its clinics for treatment of snake bites at no charge.⁴ In 2018, MSF treated 647 patients in Abdurafi, Ethiopia.

The World Health Organization published in 2019 an ambitious plan to reduce fatalities from snake bites by 50% in 2030.⁵ Four strategic aims are being pursued: 1) empower and engage communities; 2) ensure safe and effective treatment; 3) strengthen health systems; and 4) increase partnerships, coordination, and resource collaboration. This ambitious plan requires funding and cooperation from member nations at a modest cost of $82.36 million.

Acknowledgment

I wish to thank Dr. J.M. Gutierrez for reviewing the manuscript.

References

1. Gold BS, Dart RC Barish RA. Bites of venomous snakes. New Engl J Med 2002;347:347-54.
2. Gutierrez JM, et al. Snakebite envenoming from a global perspective: Towards an integrated approach. Toxicon 2010;56:1223-1235.
3. Williams D, et al. The Global Snake Bite Initiative: an antidote for snake bite. The Lancet 2010;375:89-91.
4. Williams DJ, et al. Ending the drought: new strategies for improving the flow of affordable, effective antivenoms in Asia and Africa. J Proteomics 2011;74:1735-67.
5. WHO. Snakebite envenoming—A strategy for prevention and control. Geneva: WHO, 2019. https://www.who.int/publications/i/item/9789241515641