Amoebic Pyorrhea: The 1914 Emetine Treatment of Gum Disease

In 1914, a study of patients at the Philadelphia Hospital found amoebae, single-celled parasites, in every one of the 46 people with pyorrhea alveolaris it examined, as gum disease was then called. Patients were given emetine, a drug then thought to kill amoebae while doing little to bacteria. According to the 1914 report, the amoebae disappeared and the pyorrhea was cured in 13 patients, and the researchers renamed the disease “amoebic pyorrhea” [1].

Emetine comes from the root of ipecacuanha, a South American plant, and it was shown to act against amoebic dysentery but not against dysentery caused by bacteria [2]. After a controversy, the amoeba explanation of gum disease and the emetine treatment built on it were almost totally abandoned, and dentistry came to explain gum disease through bacteria. Genetic tests have since found the same amoeba in most diseased gum pockets, and whether it helps cause gum disease is an open question again [1][3]. This page follows the story from the first description of the mouth amoeba in 1849 to the genetic studies of today.

Table of Contents

  1. Gum Disease Before 1914
  2. The Amoeba Findings of 1914 and 1915
  3. Emetine, the Anti-Amoeba Drug
  4. The Treatment and the Reported Cures
  5. What the Journals Published
  6. The Controversy and the Abandonment
  7. Emetine’s Side Effects
  8. What Replaced Emetine
  9. The Amoeba Rediscovered
  10. A Century Later: Antiparasitics and the Gums Again
  11. Key Research Papers
  12. Connections
  13. Featured Videos

Gum Disease Before 1914

Gum disease is not new. Periodontitis, the advanced form that destroys the bone holding the teeth and can end in tooth loss, “was described since antiquity”, in the words of a 2018 review that retells the history on this page [1]. The review describes three stages. Dental plaque, a sticky film of bacteria, builds up on the teeth. Gingivitis, an inflammation of the gums caused by the plaque, follows. In periodontitis, the bone and fibres that hold the teeth in place are “irreversibly damaged” [1].

In the early twentieth century the disease was called pyorrhea alveolaris. Pyorrhea comes from the Greek for “flow of pus”, and alveolaris refers to the alveoli, the sockets in the jawbone that hold the teeth. The 2018 review treats the pyorrhea of the 1914 study as the disease now called periodontitis [1].

1849: the first amoeba found in a human

The amoeba at the centre of this story was first described in 1849 by G. Gros, from samples of dental plaque. He named it “Amoebea gengivalis”. The 2018 review calls his description laconic: a brief note of the amoeba’s movement and of small sacs (vesicles) inside it. Free-living amoebae had been described since 1755, but this was the first amoeba found in humans. Gros’s paper appeared in the bulletin of a society of naturalists in Moscow, according to the review’s list of references [1]. Today the amoeba is called Entamoeba gingivalis, the gum amoeba; gingiva is Latin for the gum.

1875 to 1893: amoebae and disease

A link between amoebae and human disease was first documented in 1875, the review notes, when Lösch described the bowel amoeba now called Entamoeba histolytica, then named “Ameba coli”, and its ability to cause disease was confirmed in an animal [1]. This is the amoeba of amoebic dysentery, or amoebiasis, and the gum amoeba is its close relative [1]. Its discovery in the late nineteenth century let doctors separate the two main forms of dysentery: amoebic dysentery and bacillary dysentery, which is caused by bacteria [2].

The gum amoeba’s own ability to cause disease was “questioned early”, in 1893. No systematic study linked it to gum disease until 1914 [1].

The Amoeba Findings of 1914 and 1915

The 2018 review dates the first systematic study of the gum amoeba in gum disease to 1914, when Barrett published it in preliminary form in the dental journal Dental Cosmos. Amoebae were detected in all 46 cases of pyorrhea enrolled in the study [1].

In 1915, Smith and Barrett added 7 healthy people “from the same group of patients in the ‘Insane Department of the Philadelphia Hospital’”, the hospital’s department for people with mental illness. They said they could not find amoebae in “the detritus collected around the neck of the teeth”, the debris at the gum line [1].

Both the patients and the healthy comparison group therefore came from one hospital department, and the comparison group had seven people. The review notes that some of the early systematic studies had “a low number of participants” [1].

Names for the amoeba

In the papers of the time the amoeba goes by several names. The titles in the 2018 review’s reference list include Entamoeba buccalis (Chiavaro, 1914), Endameba gingivalis (Smith and Barrett, 1915, in the first volume of the Journal of Parasitology) and Endamoeba gingivalis (buccalis) (Craig, 1916) [1]. Buccalis means “of the cheek”, that is, of the mouth.

Cysts in the early reports

Most Entamoeba species have two forms: the trophozoite (the active, feeding form that divides) and the cyst (a resting form with a protective wall, which survives outside the body and passes the infection on). Chiavaro in 1914, Smith and Barrett in 1915 and Craig in 1916 all reported cysts of the gum amoeba. It later became “commonly accepted” that the gum amoeba does not form cysts, a view that, the 2018 review says, takes “the absence of proof as a proof of absence” [1].

Emetine, the Anti-Amoeba Drug

Emetine is an alkaloid, a nitrogen-containing plant compound, obtained from ipecacuanha, Psychotria ipecacuanha [4]. Its name comes from emetic, a substance that causes vomiting.

A 2008 history of the plant, subtitled “the South American vomiting root”, traces it from its discovery in Brazil in the 1600s to Paris later in the same century. There the physician Helvetius used it on members of the French royal court to treat “the flux”, dysentery, “with some success”. In the eighteenth century the physician and privateer Thomas Dover made it, with opium, a main ingredient of a powder that was used widely against fevers and agues (fevers with shaking chills) for the next 200 years [2].

In the early 1800s, chemists in Paris established that the dried root contained two powerful alkaloids, emetine and cephaeline, which consistently caused vomiting and diarrhoea [2]. The Paris work on emetine is told on the site’s pages on François Magendie and Pelletier and Caventou, and the plant’s story on Strychnos, Ipecac and the Plants Behind Magendie’s Medicines.

A drug against amoebic dysentery

Once the dysentery amoeba had been discovered, emetine was shown to act against amoebic dysentery but not against the form caused by bacteria [2]. It went on to be used on a very large scale: a 2020 review states that emetine has been used in tens to hundreds of millions of people to treat amoebiasis [5].

Emetine was also used against amoebic liver abscess, a pocket of pus in the liver caused by the dysentery amoeba. In a review of 50 cases seen in the Panama Canal Zone between 1920 and 1945, every patient was given emetine hydrochloride, a salt of emetine. Thirty-nine also had the abscess drained by an operation, and six of them died [6].

In laboratory studies, emetine blocks protein synthesis, the process by which cells build their proteins [7].

The Treatment and the Reported Cures

The 1914 report also described treatment with emetine. According to the 2018 review, giving emetine “caused the withdrawal of amoebae and was followed by the cure of pyorrhea in 13 patients” [1].

The cure was read as evidence of the cause. Emetine “was thought to be a specific amoebicidal alkaloid with poor bactericidal effect”: a drug that kills amoebae but does little to bacteria [1]. That belief matched emetine’s record in dysentery, where it acted against the amoebic form but not against the form caused by bacteria [2]. If emetine cleared the amoebae and the disease went with them, the amoeba appeared to be the cause. On this basis, the review says, the link between the amoeba and periodontitis “was extrapolated”, and Smith and Barrett renamed the disease “amoebic pyorrhea” and “oral endamebiasis”, an infection of the mouth with Endamoeba, as the amoeba’s genus was then often spelled [1].

Smith and Barrett’s 1915 paper on the treatment appears in the review’s reference list as “Emetin in the treatment of peridental suppurations”, with the older spelling emetin. Peridental suppurations are pus-forming infections around the teeth [1].

The review does not give the details of the treatment: how the drug was given, in what amounts, how a cure was judged, or how long the patients were followed.

What the Journals Published

Emetine treatment of pyorrhea quickly reached the journals. PubMed, the United States National Library of Medicine’s index of medical articles, lists these early articles without summaries, so only their titles are known here. The titles show what was being claimed and discussed:

Emetine for pyorrhea in Italy in the 1950s

The treatment did not disappear completely. In 1952 and 1954, four articles in Italian medical journals carried emetine and pyorrhea alveolaris in their titles. In PubMed’s English form, they are:

Paradentosis and periodontosis, spelled “periodentosis” in one title, are older names for forms of gum disease. These articles also have no summaries in PubMed, so what they reported is not known here.

The Controversy and the Abandonment

The fullest modern account of what happened next is the 2018 review. Its authors propose that the status of the gum amoeba “be reconsidered as a potential pathogen contributing to periodontitis”, that is, as a possible cause of the disease, and the account below is theirs [1].

Opinion instead of experiment

According to the review, the systematic studies linking the amoeba to gum disease, “some with a low number of participants”, “were countered by specialist opinions without formal experimental proofs”, as reported in a 1916 paper by Craig. The review calls this point “of epistemological importance”, that is, important for how knowledge is established: the case against the amoeba rested on the opinions of specialists, not on experiments [1].

“This controversy”, the review continues, “led to an almost total abandon of the etiology- and emetine-based therapy, discrediting at the same time its original scientific background”. Etiology means the cause of a disease. In other words, both the amoeba explanation and the emetine treatment built on it were dropped, and the studies behind them lost their standing [1].

Relapses and re-infection

Critics also said that the cure did not last. In 1925, Howitt wrote of relapses. The review describes these statements about a “non-permanent cure” as “unsupported by scientific data”. It adds that “the possibility of re-infections was completely ignored”: a patient whose amoebae had been cleared could have picked them up again. In the review’s words, this “casts doubts about the understanding of both pathophysiology and epidemiology of the disease at that time”, meaning how the disease develops in the body and how it spreads [1].

The 1925 test-tube experiment

Howitt also described a way to grow the gum amoeba in culture, which made it possible to test emetine on the parasite directly. The 1925 conclusion was that “emetine hydrochloride has, apparently, no very marked amoebicidal action in vitro against either of the strains of [the gum amoeba] used”. In other words, in the test tube emetine did not clearly kill it [1].

The review criticizes this test. Its figures came from a single experiment, and the concentration that stopped the amoebae’s growth was “subjectively determined”. The 1925 test put the lowest concentration that killed the amoebae at about 116.5 micromolar (μM, a measure of how much drug is dissolved) and the lowest that stopped their growth at about 38.5 μM. The review sets these beside a later study of a strain of the dysentery amoeba known to be sensitive to emetine: that strain also needed more than 100 μM to be killed outright, although its growth stopped below 1 μM [1].

From this the review concludes that “the experimental methodology to study the effect of emetine on [the gum amoeba] was not accurate”, and it treats the 1925 conclusions with caution, “because this in vitro study did not corroborate the results reported during the treatment of patients” [1].

The bacterial explanation

In the decades that followed, gum disease was explained by bacteria. The review cites a 1954 paper for the view that dental plaque is responsible for gingivitis and periodontitis, and a 1979 paper for a “specific plaque” explanation, which tied the disease to particular bacteria. The commonly accepted models today, it says, explain the progression from health to gingivitis and then periodontitis by a gradual change in the kinds and proportions of bacteria in the gum crevices, the shallow grooves where gum meets tooth [1].

Emetine’s Side Effects

The main hazard of emetine is to the heart. A 1990 review called its cardiotoxicity, its toxic effect on the heart, the drug’s “most relevant side effect”, and “well documented” [16].

Another 1990 review, of toxic damage to the heart, reported that emetine’s cardiotoxicity “occurs following chronic exposure”, that is, with repeated doses over time, “such as occurs therapeutically in amebiasis and with ipecac abuse” by people with bulimia. It noted that several mechanisms had been proposed, but that the research on them was “quite scarce” [17].

A 1977 review compared ipecac overdose with the toxicity of emetine during amoebiasis treatment. It summarized the toxicity of the ipecac alkaloids as falling mainly on the digestive tract, the heart and circulation, and the nerves and muscles [18].

Harm in people who misused ipecac

Ipecac syrup, a preparation of the root that contains emetine, has been misused to bring on vomiting. A 2005 review of 34 publications found the misuse mostly among adolescent and young adult women who were experimenting with purging or had an eating disorder. Death can occur, it reported, usually from the heart. The harms it listed included inflammation of the heart muscle (myocarditis) with abnormal heart rhythms, inflammation of the muscles (myositis), tears in the lining where the gullet meets the stomach, diarrhoea, and chemical imbalances such as low blood potassium and dehydration. When the misuse stopped, the heart and muscle damage tended to reverse [19].

A 1985 case report described a 27-year-old woman who had misused ipecac syrup for three years and developed painless weakness, mainly in the muscles close to the trunk. Electrical tests of the muscles (electromyography) and a muscle biopsy showed a muscle disease (myopathy) like the one produced experimentally with emetine. Her weakness and test results improved after she stopped taking ipecac. The authors judged that a direct toxic action of ipecac, acting through emetine, on the muscle fibres seemed responsible [20].

Laboratory studies of the heart

In guinea-pig heart tissue, emetine weakened the contraction of heart muscle and reduced the activity of the sinoatrial and atrioventricular nodes, the tissue that starts and relays each heartbeat. The researchers concluded that emetine blocks L-type calcium channels, which let calcium into heart cells with each beat, and that this “might contribute to its cardiac side effects” (1996) [21]. In isolated rat hearts, emetine eventually stopped the heartbeat (asystole) and lengthened the PR and QRS intervals of the electrocardiogram, the heart’s electrical tracing; the authors wrote in 1995 that “the cardiotoxicity of emetine continues to be a significant clinical problem” [22].

A 2026 review sums up the position: “concerns about cardiotoxicity have limited its clinical use” [4].

What Replaced Emetine

The 2008 history of ipecacuanha reports that the root and its alkaloid emetine “have now been abandoned on the grounds of toxicity”, and that they have been replaced by “safer, more effective compounds” [2].

Dehydroemetine

Dehydroemetine, as its name suggests, is a close chemical relative of emetine. Papers from 1967 and 1968 compared the two: one was titled “The comparative value of dehydroemetine and emetine in amebiasis” [23], and the other compared “the amoebicidal activity and toxicity” of natural emetine with two forms of dehydroemetine [24].

Later reports show dehydroemetine and emetine still in use for severe amoebic disease, together with other drugs:

In these reports metronidazole, another drug against amoebae, appears alongside the emetine drugs or in their place [25][26][27]. As late as 1990, an Italian review still called emetine “an important agent” for invasive amoebiasis of the bowel and amoebic liver abscess [16]. The drugs used against amoebiasis today are described on the site’s page Metronidazole and Tissue Amebicides.

The Amoeba Rediscovered

Microscope studies, 1927 to 1989

After the controversy, the 2018 review says, only a few studies looked for the gum amoeba under the microscope. Almost all of them, published from 1927 to 1989, found it in close to 100% of advanced periodontal pockets, the deepened spaces between gum and tooth in advanced gum disease. Where these studies also looked at healthy gum crevices, they found it in 0 to 26%, figures the review suggests may reflect errors in identifying the amoeba [1].

Genetic tests

Polymerase chain reaction (PCR), a method that detects an organism by copying a stretch of its genes, made it possible to identify the amoeba once one of its genes had been sequenced in 1995. The review summarizes the PCR studies that followed [1]:

From these data the review suggests that the amoeba may live in some healthy gum crevices without causing symptoms, and become associated with disease after changes in its surroundings, much as the dysentery amoeba does in the bowel [1].

The 2020 Journal of Dental Research study

A 2020 study in the Journal of Dental Research, titled “Entamoeba gingivalis Causes Oral Inflammation and Tissue Destruction”, reported these findings [3]:

The authors noted that Entamoeba species are known to resist neutrophils, antimicrobial peptides and various antibiotics, and that the gum amoeba invades and destroys tissue in ways similar to the dysentery amoeba. They described it as “a potential and, to date, underrated microbial driver of destructive forms of periodontitis” [3].

Other recent studies

What remains unproven

The 2018 review concludes that without a reliable animal model of infection, which would first need the amoeba to be grown free of all other microbes, its role as a cause of periodontitis cannot be settled by Koch’s postulates, the classic tests for proving that one germ causes one disease. Further research, the review says, has to determine whether the amoeba takes part in the disease process or is “just a bona fide marker”, a genuine sign that goes with the disease without causing it [1].

The research on the gum amoeba is followed in more detail on the site’s page Entamoeba gingivalis: The Gum Amoeba, and the flagellate on Trichomonas tenax.

A Century Later: Antiparasitics and the Gums Again

A century after amoebic pyorrhea, the same reasoning, a parasite in the gums and an anti-parasite medicine to clear it, has returned outside the medical journals. Members of online chat groups describe putting ivermectin paste, an antiparasitic medicine, directly on their gums, and report that their gum disease healed. These are personal accounts, not studies. They are gathered, with the published research around them, on the page Ivermectin for Gum Disease.

Key Research Papers

  1. Bonner M, Fresno M, Gironès N, Guillén N, Santi-Rocca J. Reassessing the Role of Entamoeba gingivalis in Periodontitis. Front Cell Infect Microbiol. 2018;8:379. PubMed PMID: 30420943
  2. Lee MR. Ipecacuanha: the South American vomiting root. J R Coll Physicians Edinb. 2008;38(4):355-60. PubMed PMID: 19227966
  3. Bao X, Wiehe R, Dommisch H, Schaefer AS. Entamoeba gingivalis Causes Oral Inflammation and Tissue Destruction. J Dent Res. 2020;99(5):561-567. PubMed PMID: 32023135
  4. Gebrehiwot W, Tok KC, Alkhashi JS, Bakare O, Gumustas M. Emetine: Advances in Pharmacology, Toxicology, and Chromatographic Approaches. Crit Rev Anal Chem. 2026;56(7):1967-1980. PubMed PMID: 40660855
  5. Bleasel MD, Peterson GM. Emetine Is Not Ipecac: Considerations for Its Use as Treatment for SARS-CoV2. Pharmaceuticals (Basel). 2020;13(12). PubMed PMID: 33261173
  6. Struve EF. Amebic abscess of the liver. Calif Med. 1950;73(2):178-80. PubMed PMID: 15426995
  7. Sidorenko VS, Cohen I, Dorjee K, Minetti CA, Remeta DP, Gao J, et al. Mechanisms of antiviral action and toxicities of ipecac alkaloids: Emetine and dehydroemetine exhibit anti-coronaviral activities at non-cardiotoxic concentrations. Virus Res. 2024;341:199322. PubMed PMID: 38228190
  8. The Cause and Cure of Pyorrhea Alveolaris by Emetine. Dent Regist. 1915;69(1):6-10. PubMed PMID: 33702873
  9. Adair R. The Treatment of Pyorrhea Alveolaris, with Special Reference to Emetine. Atlanta J Rec Med. 1915;62(1):1-11. PubMed PMID: 36020315
  10. Crenshaw W. The Roll of Emetine in the Treatment of Pyorrhea Alveolaris. Atlanta J Rec Med. 1915;62(4):179-181. PubMed PMID: 36020360
  11. The Emetine and Other Treatment of Pyorrhea. Dent Regist. 1917;71(8):379-381. PubMed PMID: 33703260
  12. Palazzi S. Emetine in the treatment of pyorrhea alveolaris and of other periodontal diseases. Rass Clin Sci. 1952;28(7):213. PubMed PMID: 13027574
  13. Sabatini G. [Emetine in the treatment of pyorrhea alveolaris and in periodentosis]. Rass Clin Sci. 1952;28(5):136-7. PubMed PMID: 12983597
  14. Sabatini G. [Emetine therapy of paradentosis (pyorrhea alveolaris)]. Accad Medica. 1952;67(6):343-8. PubMed PMID: 12996231
  15. Messina A. [Emetine in pyorrhea alveolaris]. Rass Clin Sci. 1954;30(1):21-3. PubMed PMID: 13155844
  16. Marino A, Costa R, De Natale G. [Cardiotoxicity of emetine]. Clin Ter. 1990;133(3):131-43. PubMed PMID: 2142900
  17. Combs AB, Acosta D. Toxic mechanisms of the heart: a review. Toxicol Pathol. 1990;18(4 Pt 1):583-96. PubMed PMID: 2091237
  18. Manno BR, Manno JE. Toxicology of ipecac: a review. Clin Toxicol. 1977;10(2):221-42. PubMed PMID: 15766
  19. Silber TJ. Ipecac syrup abuse, morbidity, and mortality: isn't it time to repeal its over-the-counter status? J Adolesc Health. 2005;37(3):256-60. PubMed PMID: 16109351
  20. Mateer JE, Farrell BJ, Chou SS, Gutmann L. Reversible ipecac myopathy. Arch Neurol. 1985;42(2):188-90. PubMed PMID: 2858193
  21. Lemmens-Gruber R, Karkhaneh A, Studenik C, Heistracher P. Cardiotoxicity of emetine dihydrochloride by calcium channel blockade in isolated preparations and ventricular myocytes of guinea-pig hearts. Br J Pharmacol. 1996;117(2):377-83. PubMed PMID: 8789394
  22. Pan SJ, Combs AB. Effects of pharmacological interventions on emetine cardiotoxicity in isolated perfused rat hearts. Toxicology. 1995;97(1-3):93-104. PubMed PMID: 7716796
  23. Vakil BJ, Shah SC, Moses JM. The comparative value of dehydroemetine and emetine in amebiasis. J Assoc Physicians India. 1967;15(5):223-8. PubMed PMID: 6074819
  24. Johnson P, Neal RA. The amoebicidal activity and toxicity of natural emetine, (plus or minus)-2-dehydroemetine and (--)-2-dehydroemetine. Ann Trop Med Parasitol. 1968;62(4):455-61. PubMed PMID: 4306633
  25. Haffar A, Boland FJ, Edwards MS. Amebic liver abscess in children. Pediatr Infect Dis. 1982;1(5):322-7. PubMed PMID: 7155964
  26. Ohnishi K, Murata M, Kojima H, Takemura N, Tsuchida T, Tachibana H. Brain abscess due to infection with Entamoeba histolytica. Am J Trop Med Hyg. 1994;51(2):180-2. PubMed PMID: 7915500
  27. Porras-Ramírez G, Hernández-Herrera MH, Porras-Hernández JD. Amebic hepatic abscess in children. J Pediatr Surg. 1995;30(5):662-4. PubMed PMID: 7623222
  28. Yaseen A, Mahafzah A, Dababseh D, Taim D, Hamdan AA, Al-Fraihat E, et al. Oral Colonization by Entamoeba gingivalis and Trichomonas tenax: A PCR-Based Study in Health, Gingivitis, and Periodontitis. Front Cell Infect Microbiol. 2021;11:782805. PubMed PMID: 34950608
  29. Santos JO, Roldán WH. Entamoeba gingivalis and Trichomonas tenax: Protozoa parasites living in the mouth. Arch Oral Biol. 2023;147:105631. PubMed PMID: 36764082
  30. Azadeh Y, Khademvatan S, Goharfar Z, Shahrabi-Farahani S, Jafari R. The Prevalence of Entamoeba gingivalis and Trichomonas tenax in Relation to Periodontal Disease among Patients Attending Dental Clinics in Urmia, Iran: A Cross-Sectional Study. Iran J Parasitol. 2026;21(2):247-257. PubMed PMID: 42598545

PubMed Topic Searches

  1. PubMed: Emetine and pyorrhea
  2. PubMed: Entamoeba gingivalis and periodontitis
  3. PubMed: Emetine cardiotoxicity
  4. PubMed: Dehydroemetine and amoebiasis
  5. PubMed: History of ipecacuanha

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Connections

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