Bloodletting and Malariatherapy: Treatment Methods of the Past

Those interested in the history of medicine should read the details surrounding the therapy rendered to President George Washington by his physicians in December 1799.¹ Purging, bloodletting and other methods were employed, which hastened his death.

His treatment was also discussed recently in the New England Journal of Medicine's 200^th Anniversary issue.² The authors used Washington's experience as a benchmark for measuring the remarkable progress medicine has made in the past two centuries.

Washington's Experience

There were three physicians responsible for Washington's medical care and each knew him well. The first doctor to arrive took the president's medical history. He found that the president had mild hoarseness, difficulty breathing, and was feverish and unable to swallow. A bloodletter was called to assist in treatment and 12 to 14 ounces of blood were withdrawn.

Washington was also administered molasses, vinegar and butter, and near fatal choking ensued. The doctor then applied a blister of cantharides to the president's throat, followed by more (18 ounces) of bloodletting in the morning. This was followed by the same blood removal less than two hours later.

Washington repeatedly gargled sage tea with vinegar. A fourth bleeding (32 ounces) was performed in the afternoon. Calomel (mercurous chloride) and tartar emetic (antimony potassium tartrate) were also given to the president. Both are extremely potent laxatives (purgatives).

After the fourth bloodletting, Washington's condition improved and he was able to swallow. He was returned to bed and helped into an upright position, but he continued to struggle for air. His condition began to deteriorate.

Later that day, the physicians applied blisters of cantharides to his feet, arms and legs, and then applied wheat bran poultices to his throat. Despite all of the heroic treatment, George Washington died later that evening.³

According to some 19^th century historians, Washington's physicians might have reasoned that because bloodletting (about 80 ounces) caused visible dermal vasoconstriction, it would also constrict the vessels associated with swelling in the windpipe.^4,5 In addition, the dehydrating effects of purging with calomel, diaphoresis (sweating) with sage tea and subemetic doses of tartar emetic, and blistering with cantharides would potentiate the effect.

In retrospect, the doctors' treatment should have considered the fact that the president had previously been subject to recurrent febrile respiratory infections and other acute fevers probably due to malaria and pneumonia. One of his several bouts of fever was life-threatening, and he required several weeks to recover.⁶

Treatment Methods

The scenario presented above was not unusual two centuries ago. Cathartics were major components of colonial American therapy. Physicians relied on these drugs, more than most others, to rid their patient's bodies of the noxious materials they thought produced some contagious diseases, to flush out the unbalanced humors they thought had produced their patient's symptoms by disturbing the normal tone of solid tissues.⁷

Blistering with an alcoholic solution of cantharides (Spanish flies) applied to the skin raised large welts, which the physicians reasoned neutralized the naturally occurring inflammation responsible for the patient's symptoms. Emetics, drugs that induce vomiting, were thought to strengthen weak stomach muscle fibers. Diaphoretics were thought to make the patient sweat out the disease and remove excess fluids.⁸

Bloodletting

Bloodletting was also commonly employed, and the president received prompt and expert medical care that reflected the practices of that time.⁹ Special instruments (scarificators, fleams, lancets) and cupping vessels were sold to facilitate the procedure.

Bloodletting, or phlebotomy, is likely the longest running tradition in medicine, originating in the ancient civilizations of Egypt and Greece. The practice continued for 2,500 years until it was replaced by the techniques of modern medicine. It was not until the 19^th century that people began to question its value.¹⁰

Bloodletting is one of many forms of therapy that have been discredited. One even more strange is using one disease to treat another. The most glaring example was malariatherapy: infecting patients with malaria in an effort to cure neurosyphilis.

Malariatherapy

There are few examples of one living pathogen being used to treat a disease caused by another. However, malaria parasites were used for about 40 years to ameliorate or reverse the effects of neurosyphilis, a life-threatening advanced stage of syphilis.¹¹

Syphilis progresses through a primary localized phase, a secondary phase, a latent period and, in some cases, a progressive tertiary phase involving almost any organ, but usually the ascending aorta and the central nervous system (neurosyphilis). About a third of neurosyphilitics remain asymptomatic.

Some eventually develop symptoms related to meningovascular or parenchymatous lesions, the latter reflecting destructive inflammatory and degenerative processes in the central nervous system. These are the imperative indications to induce fever to help avoid progressive mental retardation, blindness and death.

According to one researcher, "[p]atients who develop the progressive paralysis and dementia face one of mankind's most terrible diseases."¹²

These symptoms, often termed general paresis, result from a gradual loss of cortical function that may occur 10 to 20 years after an initial infection of syphilis in untreated patients. Patients suffering from these symptoms are deemed "paretics."

The Mechanisms for Fever

There is no clear answer as to why fever may benefit the treatment of paretics. Some authors claim proteinaceous materials and vaccine-induced fevers are detrimental to the spirochetes that cause syphilis.

Others suggest even low-grade fevers will improve paretics without having a clear understanding as to the cause and effect for inducing fever.¹³ Another theory is a malaria-induced fever can cause alterations in the body's immunity or biochemistry.

Authors have argued induced fevers do not "cook" the organisms, because their thermal death point is about 41˚-42˚ C or higher for six hours. These temperatures are too high for patients to bear.¹⁴

Why Use Malaria?

Fever therapy was employed because drugs used in the early treatment of syphilis were ineffective. Professor Wagner-Jauregg, in Vienna, may have been the first physician to treat syphilitic general paralysis of the insane (GPI) with malaria-induced fever. He was awarded the Nobel Prize in 1927 for his research.

Prior to this, GPI had been a killer. About 10% of all patients in mental hospitals in Britain were victims of the disease, and most would die a wretched, lingering death.¹⁵

Malaria was induced initially by administering venous blood from malaria-infected patients. Serious hazards were first encountered due to a lack of awareness of the lethal effects of certain species of human malaria parasites.

Colonel S. P. James, the first director of the Horton Laboratory in Britain, proposed a criteria to be met before a strain of the parasite could be considered safe for use in man. He was quite successful. His laboratory provided material for many thousands of victims of GPI, and some 16,000 patients in the Horton Hospital alone.¹⁶

All three species of human malaria (excluding the later accepted Plasmodium ovale) were available for therapeutic use in the 1920s: P. malariae, P. falciparum and P. vivax . The latter became the most widely used in malariatherapy primarily because the infection was easily treated with quinine and transmission by mosquito (used later) was relatively simple.¹⁷

There is no question about the efficacy of malariatherapy. It spared thousands of paretics from the horrible effects and premature death.¹⁸

However, with the advent of penicillin in the mid-1940s, it was obvious that malariatherapy was being slowly but inevitably replaced. The final curtain, however, did not come down in Britain until the 1970s, and combined therapy with penicillin, once common in the US, ceased in the mid-1960s.^19,20

When combination therapy was used, the two treatments were given concurrently or in succession. The basic course consisted of 3-10 million units of penicillin with a short course of fever therapy.²¹

A Few Surprises

In modern times, it would appear unlikely to find other instances where pathogenic organisms are currently used to treat a disease. Surprisingly, however, parasitic worms are being studied as Investigational New Drugs to ameliorate autoimmune diseases.

There are eight studies now listed on the US National Institutes of Health (NIH) website. Seven employ Trichuris Suis ova (pig whipworm)as treatment for multiple sclerosis, ulcerative colitis, autism, food allergy or Crohn's disease.²² Fortunately, the porcine variety cannot survive inside the human body for very long.

Studies suggest helminths (parasitic worms) may ease the symptoms of autoimmune diseases by increasing mucus production.^23,24 The boost in mucus production may help calm an excessively aggressive immune system. Production seems to be correlated with an increase in carbohydrate metabolism in the tissues where the helminths reside.

The other study on the NIH website, and even more strange, is one designed to inoculate celiac disease patients with human hookworm Nector Americanus to evaluate immunity and gluten sensitivity.

The second surprise relates to bloodletting. The procedure is still used to treat hemochromatosis and is the best method for removing excess iron from the body. One half-liter of blood is removed each week until the body iron level is normal.²⁵ This may require many months or even years to accomplish.

References

1. Morens DM. "Death of a president." New England Journal of Medicine. 1999; 341:1845-9.
2. Fauci AS, Morens DM. "The perpetual challenge of infectious diseases." New England Journal of Medicine. 2012;366:454-61.
3. Jackson J. Memoir on the last sickness of General Washington and its treatment by the attendant physicians. Privately printed. 1860.
4. Solis-Cohen S. "Washington's death and the doctors." Lippincott's Monthly Magazine. 1899;64:945-52.
5. Schneeberg NG. Letters to the Editor. New England Journal of Medicine. 2000; 342:1222.
6. Red Gold. Public Broadcasting System. www.pbs.org/wnet/redgold/printable/p_bloodletting.html. Accessed 2 February 2012.
7. Estes JW. "George Washington and the Doctors." Medical Heritage. 1985.
8. Chernin E. "The malariatherapy of neurosyphilis." J Parasit Dis. 1984; 70(5):611-17.
9. Bond H. "General paralysis and its treatment by induced malaria." Her Majesty's Stationery Office. London.
10. "A final curtain." BMJ. 14 June 1975.
11. Crawford GM. "Syphilis." New England Journal of Medicine. 1948; 238:152-9.
12. Becker FT. "Induced malaria as a therapeutic agent." In Malariology. 84.
13. US National Institutes of Health. clinicaltrials.gov/ct2/results?term=Trichuris+suis. Accessed 8 March 2012.
14. Jabr F. "For the good of the gut: Can parasitic worms treat autoimmune diseases." Scientific American. 1 December 2010.
15. Wickelgren I. "Can worms tame the immune system?" Science. 2004; 305:170-1.
16. PubMed Health. www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001368/. Accessed 13 March 2012.