Focal Infection

The Focal Infection Theory: Appraisal and Reappraisal

This paper discusses the past, present, and future of the focal infection theory of disease. A focal infection is a localized or general infection caused by the dissemination of microorganisms or toxic products from a focus of infection. The resurgence of the focal infection theory of disease has been greeted with great enthusiasm in some quarters; however, the present evidence for the relationship of oral microorganisms and systemic disease is very limited due not only to a dearth of prospective studies and a complete lack of interventional studies but also to very significant methodological difficulties associated with the clinical studies that have been performed.

Ideas rarely disappear completely, and so the focal infection theory of disease is now making a comeback after most applications of it were disproved by the emerging science of the 1930s and 1940s. It has been kept alive all these years by the American legal tort system as health care practitioners and dentists in particular are still blamed routinely for virtually any infection in the body that can be remotely associated with a distant putative source such as the oral cavity. Others may now envision focal infection as a means to convince patients that extensive dental treatment is required to "prevent" coronary artery disease or other maladies "caused" by dentally induced bacteremias or to give dentistry greater medical significance by linking oral microorganisms with systemic disease causation. It goes unappreciated that dental treatment could just as easily be considered the "cause" of patient systemic disease placing dentists in legal jeopardy.

It is timely to review the history of the focal infection theory of disease in the context of modern health care. Scientific methods have improved such that we can revisit this concept with greater acumen and the realization that this moment in time differs from the past in that we are now much more under the scrutiny of the legal profession for good or ill. Our hypotheses must now be more rigorously tested before public media dissemination, and we must scrupulously avoid the common practice of presenting doctrine without data. Otherwise, we will face an avalanche of ill-conceived lawsuits and risk having our scientific credibility further eroded in the public eye.

A focus of infection has been variously described but probably best as a circumscribed and confined area that:

* Contains pathogenic microorganisms;

* Can occur anywhere in the body; and

* Usually causes no clinical manifestations.¹

A focal infection is a localized or general infection caused by the dissemination of microorganisms or toxic products from a focus of infection.¹ Some of its harshest critics have euphemistically described a focus of infection as: "anything that is readily accessible to surgery."²

Foci of infection have typically been said to arise from the tonsils, oral cavity, or sinuses, but also from the prostate, appendix, bladder, gall bladder, and kidney with pyorrhea alveolaris (periodontitis), alveolar abscesses, and pulpless teeth (treated or untreated) being the principal oral culprits and the viridans group streptococci as the prime microbial pathogens.^1,3,4 Focal infections ascribed to foci of infection include: arthritis, neuritis, myalgia, nephritis, osteomyelitis, endocarditis, brain abscess, skin abscess, pneumonia, asthma, anemia, indigestion, gastritis, pancreatitis, colitis, diabetes, emphysema, goiter, thyroiditis, Hodgkin’s disease, obscure fever (fever of unknown origin), and nervous diseases "of all kinds."^1,3-5 The pathways for the dissemination of infection are by direct spread or by blood or lymphatic metastasis of the infecting organisms, their toxic products, or tissue immunologic reactions to the organisms or their products.⁶

The application of the focal infection theory eventually fell from scientific favor for many reasons including the:

* Improvement in dental care;

* Advent of antibiotics;

* Small percent of "cures";

* Inability of science to prove the value of the theory;

* Eventual unfavorable reaction to the "orgy"of dental extractions and tonsillectomies;

* Inability to replicate the experiments of its advocates;

* Occasional exacerbation of the disease by the removal of the focus; and

* Lack of controlled clinical studies.^7,8

This introduction to the focal infection of disease should not be construed to mean that the theory has no basis in fact. There is little doubt that under certain circumstances microorganisms can move from one area of the body to another to establish their customary pathology in another locale. It would be untenable to think otherwise. Bacteria metastasize to the heart, brain, kidney, liver, joints, gastrointestinal tract, and skin from other areas of the body, including the mouth. The key questions are how often does this occur and is there any reasonable and prudent way to prevent such metastasis with an acceptable risk-benefit ratio in this era of microbial resistance to antibiotics.

The ensuing discussion of the history of the focal infection theory of disease is important because many of its present advocates appear to be unfamiliar with its history, fail to distinguish between acute and chronic infections (confusing endocarditis with the purported oral bacterial causation of chronic heart disease, two vastly different pathologies), do not expose current theories to the rigorous scientific scrutiny and methodologies currently available, commit the same mistakes as earlier investigators regarding extrapolation beyond the data, and appear unaware of the medicolegal consequences of unfounded theories. Let us know the past so as not to repeat it.

The Past

The idea that removing a focus of infection could prevent or cure systemic diseases goes back to ancient times, as Hippocrates is said to have reported the cure of arthritis after removal of a tooth.⁹ In the early 1800s, Benjamin Rush, an American physician and signer of the Declaration of Independence, is said to have observed the cure of a case of arthritis of the hip by tooth extraction.⁹ The Americans were much behind the Europeans in the acceptance of the germ theory of disease, and American science virtually disappeared in the 1850s only to see a major resurgence with Koch’s demonstration of the causation of tuberculosis by Mycobacterium tuberculosis in the early 1880s.¹⁰ Shortly thereafter, bacteriology became a scientific fad with many excesses¹⁰ including the autointoxication theory (that bacterial stasis in the colon caused systemic disease), which reached its apogee in 1913 as the purported cause of gastric cancer, peptic ulcer, neuritis, headache, endocarditis, mental apathy, stupidity, arthritis, and various other disorders.⁵ The purposeful removal of the colonic microbial flora by purging is still practiced today with possibly the only result being a decrease in colonization resistance (ability of the intestinal flora to resist invasion by foreign organisms) and an increased risk of colon infections.

In 1890, the dentist and physician, W.D. (Willoughby Dayton) Miller published "The Micro-Organisms of the Human Mouth: The Local and General Diseases Which Are Caused by Them" in Germany.¹¹ A year later in a Dental Cosmos article,¹² Miller used the term "focus of infection" for the first time. Although he was writing before the discovery of radiographs, Miller did not necessarily recommend removing teeth considered to be a focus of infection and also suggested "treating and filling root-canals." In the same issue of Dental Cosmos, he emphasized the importance of disinfecting instruments so as not to spread infection.¹³

In 1900, the English physician William Hunter reported in the British Medical Journal on "Oral Sepsis as a Cause of Disease" blaming poor dental health and "conservative dentistry" (the preservation of the dentition by dental treatment) as the cause of the plethora of systemic diseases listed above.¹⁴ However, it was not until his address to the medical students at McGill University in Montreal in 1911^15,16 that the dental and medical professions took serious notice of focal infections: "No one has probably had more reason than I have had to admire the sheer ingenuity and mechanical skill constantly displayed by the dental surgeon. And no one has had more reason to appreciate the ghastly tragedies of oral sepsis which his misplaced ingenuity so often carries in its train. Gold fillings, crowns and bridges, fixed dentures, built on and about diseased tooth roots form a veritable mausoleum over a mass of sepsis to which there is no parallel in the whole realm of medicine and surgery. A perfect gold trap of sepsis of which the patient is the proud owner and no persuasion will induce him to part with it, for it cost him much money and it covers his black and decayed teeth.

"The worst cases of anemia, gastritis, colitis, obscure fevers, nervous disturbances of all kinds from mental depression to actual lesions of the cord, chronic rheumatic infections, kidney diseases, are those which owe their origin to, or are gravely complicated by the oral sepsis produced by these gold traps of sepsis. Time and again I have traced the very first onset of the whole trouble to a period within a month or two of their insertion. This form of sepsis is particularly severe and injurious, because it is dammed up in the periosteum and alveolus and can not be eliminated by any ordinary medical antisepsis the doctor can administer, moreover it being locally painless and insidious in action, it goes on accumulating in severity without giving any symptom or warning."^15,16

Hunter apparently knew that there were many good dentists: "For while a large body of that profession are engaged in dealing successfully with the difficult problems of dental disease and of oral sepsis, another body is no less steadily engaged in promoting sepsis of the worst character and degree by ignoring the fundamental principles connected with the anatomy, physiology, and pathology of the tissues with which they deal."^15,16

Modern restorative dentistry and endodontic therapy were essentially a development of American ingenuity, and it is possible that rival interests between Britain and America were a part of this problem;¹⁷ yet, in the words of E.C. Kirk: "Unfortunately, however, Dr. Hunter in his enthusiasm for his cause has failed to make as plain as he should make it the distinction which he has clearly implied between such work skillfully executed and intelligently applied and the monstrous anatomical and physiological insults which are palmed off upon an ignorant public by equally ignorant charlatans under the general term of American crown and bridge work."¹⁶

Sir William Osler declared that the neglect of the teeth of the people in England "is a national disgrace,"¹⁶ a fact possibly overlooked by Hunter. Hunter’s condemnation of "American" dentistry led to the British dental profession largely subscribing to his opinions until after World War II¹⁷ and the creation of a nation of the edentulous and dentured. Hunter’s opinions, however, were very useful in the quest of both the American and British dental associations for greater professional status and elimination of the untrained, uneducated, and unscrupulous "practitioners" by licensing requirements.¹⁸

In 1912, the physician Frank Billings formally and independently introduced the concept of focal infection to American physicians.^19,20 Again, as with Hunter, he reported a number of case observations where he ascribed distant infections to various pathologies and went the further step to state that cures were attained with tonsillectomies or dental extractions.

Billings was of the opinion that "most of the infections and contagious diseases may be classed as preventable; most of them are filth diseases, and they cannot exist in the presence of perfect cleanliness." This was not an unreasonable position at the time of Billing’s statement (1898) as public and professional sanitation was in its infancy and cholera, rheumatic fever, typhoid, typhus, poliomyelitis, and other social contact diseases were endemic and at times epidemic. Billings further claimed that cultured organisms from arthritic patients and injected into rabbits caused arthritis in these animals.²¹

E.C. Rosenow was an ardent pupil of Billings at the Rush Medical College and later conducted experiments at the Mayo Clinic where he developed the theories of "elective localization"²² and "transmutation"²³ in which he claimed that microorganisms had affinities for certain organs of the body and that microorganisms could change their characteristics: viridans streptococci could "transmutate" into beta-hemolytic streptococci or pneumococci. The theory of bacterial transmutation conveniently explained why other researchers were unable to duplicate the results of Rosenow as the original bacteria injected into animals had "transmuted" to other bacteria.²⁴ As prominent physicians such as Charles Mayo²⁵and Russell Cecil²⁶ joined Hunter, Billings, and Rosenow in advocating the focal infection theory of disease and its remedy by surgery, millions of tonsils and teeth were removed in what was later described as an "orgy of extractions."²⁷

Many physicians recommended surgical procedures, particularly extractions or tonsillectomies, as the only sure cure for various diseases. Many physicians and dentists recommended extracting all endodontically treated teeth ("one hundred percenters"),¹⁷ some recommended extracting all nonvital or "suspicious" teeth, and others recommended that all teeth be removed for the sake of prevention as well as treatment ("therapeutic edentulation").

In 1918, the dentist Josef Novitzky assailed dentists who performed root canal therapy as "almost criminal,"²⁷ and Widdowson quoted a well-known dentist who claimed that a dentist who did crown and bridge work should receive "six months hard labour."²⁸ Fortunately reason began to prevail in 1920 when C. Edmund Kells, the founder of dental radiography, presented an entirely opposite view of criminal behavior: that indiscriminate extraction of teeth to cure focal infections was "the crime of the age" and recommended that dentists refuse to operate upon physicians’ instructions to needlessly remove teeth.²⁹

In 1919, Lillie and Lyons recommended tonsillectomy in every case of arthritis promising a marked improvement in up to 80 percent of all cases,³⁰ and Cotton claimed "impregnable" evidence in the Journal of Dental Research that dental extractions or tonsillectomy prompted cure or improvement in mental disease and insanity.³¹ Cotton advocated the extraction of all capped and "pivot" teeth and the removal of all fixed bridgework while acknowledging that 5 percent of such work was good but the risk was too great to leave alone. Two hundred thousand tonsillectomies were performed every year in England and Wales and "It may be inferred that in many cases financial considerations played a role since the operation is three times as common among the well-to-do as among the poor."³² In the United States, the tonsillectomy rate was double in large income families as compared to poor ones.³²

As the 1930s dawned, observations appeared that: "If this craze of violent removal goes on, it will come to pass that we will have a gutless, glandless, toothless -- and I am not sure that we may not have , thanks to false psychology and surgery -- a witless race"³³and as reported in the American Journal of Ophthalmology: "Stripped of tonsils and teeth, often the victim of colonic irrigation, abdominal, and genito-urinary operations, the patient may finally be reduced to only those organs necessary for existence, while all the time his ocular disease progresses remorselessly to blindness."³⁴

In 1938, Cecil (a former proponent of focal infection) and Angevine concluded that "focal infection is a splendid example of a plausible medical theory which is in danger of being converted by its enthusiastic supporters into the status of an accepted fact."² and published an analysis of 200 cases of rheumatoid arthritis that documented no benefit of tonsillectomy or dental extractions and which, in some cases, resulted in exacerbation of the arthritis.² The authors concluded that "the time has arrived for a complete revaluation of the focal infection theory." In 1939, Vaizey and Clark-Kennedy demonstrated that those made edentulous for "medical" reasons ("the clean sweep," "therapeutic edentulation") subsequently developed arthritis and dyspepsia. Rather than being a cure for indigestion, they observed, the lost teeth caused chewing difficulties; and such edentulism was actually a cause of indigestion.³⁵

In 1940, Reimann and Havens published the most influential critique of the focal infection theory with the findings that:

* The theory of focal infection has not been proved;

* The infectious agents are unknown;

* Large groups of people whose tonsils are present are no worse than those whose tonsils are out;

* Patients whose teeth and tonsils are removed often continue to suffer from the original disease for which they are removed;

* Beneficial effects can seldom be ascribed to surgical procedures alone;

* Beneficial effects that occasionally occur after surgical measures are often outweighed by harmful effects or no effects at all; and

* Many suggestive foci of infection heal after recovery from systemic disease, or when the general health is improved with hygiene and dietary measures.³²

The focal infection theory was (is) elegant in its simplicity and offered quick and easy (as well as lucrative) solutions to a myriad of problems for which medicine had no answers. It also afforded medicine the chance to deflect the blame from its ignorance to relative defenseless and unwitting victims: dentists and patients. As in all eras of great discoveries (in this case the germ theory of disease), the revelation was carried to the extremes of extrapolation. All of its proponents were infected with the concept that "after it, because of it" for which even today there is no vaccine. Bearing the above in mind, it is useful to now examine the resurgence of the focal infection theory of disease in its newer guises.

The Present

The resurgence of the focal infection theory of disease has been greeted with great enthusiasm in some quarters^36-38 particularly as there is now possible limited evidence that periodontal microbial pathogens may be a risk factor for cardiovascular disease. The current evidence for such an association has been reviewed in a companion paper in this journal issue.³⁹ That oral microorganisms/oral disease could be responsible for some forms of systemic diseases is attractive as it would give dentistry greater professional participation in the health care process, would stimulate basic and clinical research in this area, and encourage the public to take better care of their mouths. It is always wise to resist generalizations from limited data (particularly via the media), and the profession should be well aware of the consequences of encouraging patient treatment without documented benefit.

That bacteria may move from the oral cavity to other areas of the body has never been seriously challenged for good reason: It happens. Viridans group streptococci, particularly Streptococcus milleri, have been isolated from brain, liver, and pulmonary abscesses; cardiac vegetations; sinuses; urinary tract infections; and the mediastinum.^40-43 The most common cause of both brain abscesses and bacterial endocarditis is Streptococcus sanguis.⁴⁴ Periapical abscesses have been blamed for necrotizing fasciitis, cavernous sinus thrombosis, mediastinal abscesses, and fever of unknown origin.⁴⁵ That such metastatic infections occur should not be the major issue but rather how often do they occur and are they preventable within any reasonable risk-benefit ratio.

The risk for a brain abscess after dental treatment has been calculated in a worst case scenario to be 0.09 to 0.84 cases per million population per year (one chance in a million to one in 10 million).⁴⁴ If we accept that dental treatment-associated bacteremias may cause prosthetic joint infections (although there has never been a single well-documented case of such an occurrence), then the worst-case scenario has been estimated to be 0.03 percent to 0.04 percent (30 to 40 cases per 100,000 prosthetic joints).⁴⁴ If we then agree that bacteremias are 1,000⁴⁶ to 8,000⁴⁷ times more likely to be caused by daily oral procedures such as oral hygiene and eating than dental treatment, then the worst-case scenario for dental treatment causation of prosthetic joint infections is one chance in 2.5 million to 20 million patients with orthopedic prosthetic joints.⁴⁴

A recent study of patients with endocarditis who either did or did not have dental treatment in a reasonable interval before the onset of the disease concluded that there was no relationship between dental treatment and bacterial endocarditis (although the study did demonstrate a strong relation between cardiac valve pathology and endocarditis).⁴⁸ Other studies have also supported a very low risk rate for endocarditis with dental treatment^49,50 as have a number of literature analyses.^44,46,51-54 The most recent American Heart Association guidelines for the prevention of endocarditis clearly state that "the vast majority of endocarditis due to oral organisms is not related to dental treatment procedures."⁵⁵

It is very often exceedingly difficult if not impossible to determine direct causation between oral bacteria and metastatic infection sites, particularly regarding temporal associations as the organisms from the mouth and infected site are rarely examined to see if they are genetically identical, although techniques such as the polymerase chain reaction are available. Other difficulties are also apparent. The term "alpha-streptococcus" is often equated in medicine with viridans group streptococci although enterococci, Streptococcus pneumoniae, and group D streptococci also turn blood agar green. The authors are unaware of a single case of endocarditis due to the common periodontal pathogens, Porphyromonas gingivalis or Prevotella intermedia, probably because the oxygen-rich environment of the heart is not conducive to anaerobic growth. Periodontal pathogens are rarely if ever a cause of endocarditis.⁴⁴ It is also poorly appreciated that viridans group streptococci are ubiquitous microorganisms found not only in the oropharynx, but also in the nose, large intestine, female genitourinary tract, and on the external genitalia.⁵⁶ Considering the epidemic of antibiotic-resistant microorgansims,⁵⁷ antibiotic toxicity and allergy,⁵³ and the very low risk of serious sequellae to metastatic oral microbes, a systemic chemotherapeutic approach to prevention (endocarditis antibiotics prophylaxis would be a notable exception⁵⁵) has a generally unacceptable risk-benefit ratio.

The Future

The present evidence for the relationship of oral microorganisms and systemic disease, particularly that of the coronary arteries, is very limited due not only to a dearth of prospective studies and a complete lack of interventional studies but also to very significant methodological difficulties associated with the clinical studies that have been performed.³⁹ Also, the occurrence of metastatic infections from the mouth to distant bodily sites is rare. It would then appear wise to refrain from embracing the focal theory of infection in any guise until the proper research is conducted and corroborated by independent investigators. Presently all we have is the resurgence of a previously discredited theory with no more substantial evidence now than then. The dental profession should refrain from the temptations to gain economically from the focal infection theory, to justify dental treatment solely on the basis of prevention of systemic disease, or to use this theory to criticize another practitioner’s efforts. What we need now is sound science not jubilation that focal infection is the savior of dental practice.

Authors

Thomas J. Pallasch, DDS, MS, is a professor of pharmacology and periodontics at the University of Southern California School of Dentistry.

Michael J. Wahl., DDS, is a private dental practitioner in Wilmington, Del.

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To request a printed copy of this article, please contact/Thomas J. Pallasch, DDS, MS, USC School of Dentistry, University Park MC-0641, Los Angeles, CA 90089-0641.