Carriers in infectious diseases ; a manual on the importance, pathology, diagnosis and treatment of human carriers

Front matter

Class .^ROiii Book ■ HS~

Copyright N?.

CBEflilGHT UEPOSIC

Preface

In writing this book, the author has attempted to prepare a manual on that young but rapidly growing specialty in preventive medicine, which, for want of a better term, may be called carrier work. The subject has been treated as a part of general medicine and surgery, and the book is intended to be of practical value to medical students and physicians, especially those with public health responsibilities. The didactic or text book method of presentation has; therefore, been adopted, rather than the monographic. There are already two monographs on this subject in English: "The Carrier Problem in the Infectious Diseases," by Ledingham and Arkwright, and "Human Infection Carriers," by Simon. The writer's aim is not to compete with these valuable works, but to supplement them. No effort is made to develop the subject historically or bibliographically, except to emphasize certain points or to refer to recent summaries. The idea has been to give a systematic exposition of current medical theory and practice as relates to carriers. Some idea of the amount of work, which has been and is being devoted to this subject, can be gathered from the fact that there are in the catalogue of the Surgeon- General's Library, on typhoid carriers alone, over three hundred references to recorded experiences. An effort has been made to collect, from these sources and from practical experience, the lessons that survive the test of time and trial and thus deserve a place in the program for the future.

The writer has had personal experience with carrier problems from several different angles. On the theoretical side, anyone who in these days works intelligently for the health of groups, as well as of individuals, soon realizes that carriers as well as cases must be considered in any rational and radical program for the control of the infectious diseases. In attempting to study carriers, it was found that animal experimentation afforded a good method of approach, as human carriers are not always available when desired and clinical conditions often cannot be analyzed experimentally.

6 PKEFACE

Some personal experimental work was, therefore, done on the mechanism of carrier production, and on the possible use of animals in solving carrier problems. On the practical side, it has fallen to the author's lot to investigate the origin of several epidemics in which the carrier possibility was a proved or unproved factor. Considerable laboratory work in the bacteriological diagnosis of carriers, the virulence of cultures, etc., has also been done in the course of routine duties. Clinically, before and especially during the war, I had an opportunity to test the results of surgical treatment of typhoid, diphtheria and streptococcus carriers and am convinced of the value of these measures. During the war, survey and carrier work, which was done on a larger scale than ever before, yielded much new information. Many questions of policy and feasibility were also raised. Some personal experience with such problems has been valuable in orienting the subject. Several years' experience in teaching infectious diseases at the Army Medical School has also emphasized the importance of the subject of carriers in a general course. Altogether, therefore, from personal experience, the author believes that there is a place for a practical manual on carriers. The shortcomings of this attempt are realized, but it is hoped that these pages may assist in a more systematic understanding of the problem and may lead to more effective use of our knowledge.

It is a pleasure as well as an obligation to acknowledge much indebtedness to the staff and organization of the Laboratories of the Army Medical School, under the Directorship of Lieutenant- Colonel Charles F. Craig, and to the Curator of the Army Medical Museum, Major G. R. Callender, of the Medical Corps of the Army.

Carriers exist in the infectious diseases of animals and plants as well as of man, and the comparative or biological method is as valuable in the study of carriers as it is in other branches of medicine. In addition, there are, of course, practical carrier problems for veterinarians and horticulturists. Plants differ in so many respects from man and animals and so little is known about their mechanism of immunity, that this field can not be discussed here with much advantage. Carriers among animals, however, are better understood and are analagous to human

PREFACE 7

carriers. In fact, all our animal experimentation is a part of veterinary medicine. Moreover, in several of the infectious diseases, animal carriers directly concern physicians. In order to cover this interrelated field, Captain R. A. Kelser, of the Veterinary Laboratory of the Army Medical School, has contributed a section on carriers in veterinary medicine.

This publication is made with the permission of the Surgeon- General, United States Army, who, however, is not responsible for any opinion expressed or conclusions reached herein.

CONTENTS Introduction. Definitions 13

PARTI. GENERAL CONSIDERATIONS

I. Importance 21

II. Pathology 25

III. Diagnosis 34

IV. Treatment* 37

Part II. Special Diseases

V. The typhoid fevers 45

VI. Cholera ' 60

Vll. The dysenteries 64

a. Bacillary 64

b. Protozoal 66

VIII. Helminthoses 70

IX. Diphtheria 72

X. Epidemic meningitis 79

XI. Pneumococcus pneumonia 87

XII. Streptococcus infections 90

XIII. Other respiratory infections 97

1. Influenza 97

2. Vincent's angina 98

3. Tuberculosis 99

4. Diseases of unknown etiology or due to filterable viruses. 100

XIV. Blood diseases 101

1. Malaria 101

2. Other diseases of the blood 102

3. Skin diseases 103

XV. Sexual diseases 104

1. Syphilis 104

2. Gonorrhoea 106

Part III. Summary

XVI. The relations of phorology to preventive medicine Ill

1. The place of carrier work in preventive medicine Ill

2. The method of carrier work 114

3. Carrier work in the military services 116

10 CONTENTS

PART IV. CARRIERS IN VETERINARY MEDICINE XVII. Carriers of organisms pathogenic for both man and the lower

animals 123

1. Micrococcus melitensis 123

2. Bacillus tuberculosis 125

3. Organism of the Salmonella, Enteriditis or Gaertner

group 129

4. Bacillus tetani 132

5. Bacillus oedematis maligni 134

6. Bacillus anthracis 135

7. Bacillus mallei 136

8. Bacillus diphtheriae 137

9. Bacillus pestis 139

10. Bacterium tularense 140

11. Bacillus erysipelatis suis 141

12. Miscellaneous facultative-pathogenic bacteria 143

1. Leishmania canis 145

C. Carriers of filterable viruses 147

1. Virus of foot-and-mouth disease 147

XVIII. Carriers of organisms pathogenic for animals and possibly for

man 151

1. Streptococcus of infectious mastitis of cattle 151

2. Bacterium abortus (Bang) 153

1. Trypanosomes 156

2. Other protozoal and metazoal infections 159

XIX. Carriers of organisms pathogenic for lower animals only 161

1. Bacillus bipolaris septicus 161

2. Bacillus necrophorus 162

3. Bacillus paratuberculosis 164

4. Bacillus pullorum 166

1. Piroplasma bigeminum and Piroplasma bovis 167

2. Piroplasma caballi and Nuttallia equi 170

C. Carriers of filterable viruses 171

1. The virus of equine infectious anemia 171

2. The virus of contagious pleuro-pneumonia of cattle . . 173

3. The virus of equine influenza 175

4. The virus of hog cholera 176

XX. Conclusion 177

Index 183

CONTENTS 11

ILLUSTRATIONS

1. Section of tonsil from diphtheria carrier 27

2. Section of tonsil showing yeast-like parasite 28

3. Section of tonsil with crypts injected with lampblack and paraffin. 29

4. Section of gall bladder of typhoid carrier 31

5. Section of gall bladder in experimental typhoid carrier in rabbit. 32

6. Picture of duodenal tube 52

7. Gall bladder from typhoid carrier who was cured by cholecys-

tectomy 56

8. Gall bladder from typhoid carrier who was not cured by cholecys-

tectomy 57

9. Kidney from typhoid carrier who was cured by nephrectomy 58

10. Section of tonsil of diphtheria carrier 75

11. Section of tonsil of streptococcus carrier 93

Introduction

It is common knowledge that the recognition of the infectious nature of many diseases made a new era, both in the theory and in the practise of medicine. On the philosophical side, the parasitology of Pasteur and Koch soon became linked up with Darwin's grand conceptions and has taken its place in the scheme of the struggle for existence and natural selection. On the practical side, the "germ theory" has revolutionized medicine by giving us much new insight into and control over many diseases.

Within the realm of the infectious diseases, the concept of the so-called healthy carrier was also epoch making. It pointed to a new possibility in the outcome of the fight of man against his parasites. The patient may recover with complete destruction of the parasite. The parasite may win with death or disability of the patient. But there may also be a draw with the production of a carrier. The appreciation of this possibility lead to fresh progress in the explanation and prevention of infections. The original observations are accredited to Koch in his work on cholera in 1892-1893. Work on typhoid fever developed the subject and by degrees carriers have been given a regular place in the picture of infectious diseases. Most of our exact knowledge has come from work on typhoid and diphtheria carriers.

It may be accepted that the continued existence of many infectious diseases depends, to a considerable degree, on the spread of pathogenic parasites from apparently healthy and usually immune individuals to susceptibles. The strength of the carrier program rests on the possibility of detecting such parasites and such susceptibles and of keeping them separated. This possibility, however, depends on scientific knowledge and on administrative control, neither of which is complete. In many diseases we have no ready means of determining the virulence of the parasite in the possible carrier or the susceptibility of the possible host. In addition, when we have this knowledge, it is often impossible to apply it practically on a large scale on account of the limitation of laboratory facilities and because the affairs of life are not run purely for preventive medicine. The carrier program, therefore, admittedly has its weak points. However, with the increase of the exactness of our knowledge and with the generalization of scientific education, social consciousness is calling for more and more carrier work. The specialist and the man on the street are gradually joining their forces for a strong combined attack on the carrier problem.

The greatest need in carrier work at present is the intelligent cooperation of medical men in making a workable synthesis. Too often the bacteriologist knows only his germs, the physician knows only his patient, and the sanitarian knows only the gross situation in the field. Each tries to construct the whole story from his own point of view and as a result the literature contains many assertions, half truths and guesses which hinder real progress. The only way to improve is for all concerned to get closer to the realities and to cooperate with mutual self-restraint.

In view of the increasing importance of the subject, a special terminology is desirable. The term "bacteriophoria" has been proposed to indicate the condition of carrying bacteria. But this term does not include the carrying of protozoa and metozoa and does not cover the science and art of the subject. A more precise word would be parasitophorology, or for short, phorology. A carrier would be a phore, or a phorist, and a worker on carriers would be a phorologist. While these words might lend themselves to ridiculous developments, such as treponemaphorologist, it appears that phorology and phorologist (medically speaking) might be useful at times and they are suggested for consideration.

A carrier is an individual who harbors and transmits pathogenic parasites without showing the usual evidences of infection. Some carriers show no clinical or pathological evidences at all and are really healthy, but the most important carriers are only apparently healthy, because, on careful examination, they do show signs or symptoms of local infection. Although in some instances the parasites are carried purely mechanically, in the worst carriers they have a home which is usually a slight chronic inflammatory lesion of a mucous membrane. The absence of disease in carriers is due to the fact that the carrier either (1) is in the stage of incubation; (2) has a general but not a local immunity; or (3) is too slightly infected to show symptoms.

Carriers may be classified as follows :

1. True carriers

A. Incubationary carriers — temporary

B. Convalescent carriers — temporary, chronic and relapsing

C. Contact carriers — temporary and chronic, primary and secondary.

2. Pseudo-carriers

3. Possible carriers

1. True carriers. The parasites are pathogenic and virulent. Questions of relative virulence are of course involved and many of them are unsettled at present. The weight of evidence, however, is against sudden changes of virulence and in true carriers, according to actual tests or reasonable assumption, the organisms are of sufficient virulence to infect.

A. Incubationary or precocious carriers are infected and infective individuals in the incubation period of various diseases. These carriers are recognized as especially dangerous in the acute exanthemata. They have also been recognized in cerebrospinal meningitis, typhoid, cholera, and other diseases. In some carriers the germ apparently has a "resting" period much longer than the clinical incubation period. Even with the ordinary period of days and weeks, an apparently healthy person may in this way spread trouble in many directions.

B. Convalescent carriers are of three kinds, the temporary, chronic and relapsing.

1. Every case must pass through the temporary convalescent carrier stage and fortunately most cases terminate in this way. There is a clean-up fight between the body cells and the parasite with complete victory for the tissues. Along with convalescence or soon afterwards, the patient is disinfected by immune bodies and phagocytes and does not infect his environment or immediate contacts.

2. A small percentage of convalescents, however, become chronic carriers. These form the bulk of the carrier menace and problem. The microorganisms perpetuate themselves from carrier to case and from case to carrier. This is the vicious circle which must be broken to win the fight against infectious diseases.

3. Relapsing carriers. A group of this kind is useful as it covers convalescent carriers who later relapse into cases. Examples of such carriers are found especially in protozoal infections in which the immunity is not as sharp as in bacterial infections. The point of difference between a chronic or latent case and a relapsing carrier is the slowly progressive nature of the infection in cases and a complete balance, even if temporary in carriers. If the carrier conception is broadened to include the infection of one organ within the individual by a carrier lesion in another organ, cases of focal infection can be considered relapsing carriers.

C. Contact carriers or "healthy" carriers are those who acquire the parasite from association with cases or carriers without developing the disease themselves. Such carriers are already immune. Differential diagnosis between a contact and incubationary carrier can be made in most cases only by the outcome. Contact carriers are usually temporary, but may become chronic if there already exists some predisposing chronic focus. Thus, an immune contact carrier with a negative Schick test and an obstructed nasal passage may carry diphtheria bacilli until the deformity is corrected. Contact carriers may be primary, that is, infected by a case, or secondary, infected by another carrier. The importance of pure contact carriers has been exaggerated. Many so-called contact carriers are really convalescent carriers after mild infections, as has recently been emphasized by Craig.

Contact carriers might include also "mechanical" carriers such as surgeons with contaminated hands, but such carriers as well as inanimate objects which carry infection by indirect contact are best considered under personal hygiene and general sanitation. There is nothing distinctive about their carrier relationships.

2. Pseudo-carriers. A group should be made for carriers of non-pathogenic and non-virulent organisms. These may be called pseudo-carriers. In any extensive carrier work suspicious organisms are found which, however, on further examination, turn out to be of no importance. In the meantime, the patient may have been handled as a true carrier. The diagnosis should be changed to that of pseudo-carrier. Such carriers are especially well recognized in diphtheria.

3. Possible carriers. A group of possible carriers may well be made to account for the considerable number of persons who carryorganisms of uncertain significance. These organisms at present can neither be proved nor disproved to be of importance, on account of the inadequate state of our knowledge. Under this heading would come many carriers of streptococci, influenza bacilli, and various intestinal organisms. With increasing knowledge this group will naturally disappear as the members of it are distributed among the true and psuedo-carriers.

Convalescent carriers have been called active and contact carriers, passive. These terms are valuable in emphasizing the difference between the active focus of multiplication in convalescent carriers and the usual absence of a home in the contact carrier, but they are somewhat misleading as all true carriers are active from the point of view of the parasite.

Cases have also been called acute carriers, but this is believed to be an unfortunate use of terms, as it is desirable, on many grounds, to distinguish as clearly as possible between cases and carriers.

Insects which transfer pathogenic microorganisms are often called carriers. In malaria, the mosquito is as an essential part of the carrier mechanism as the formation of gametes in the blood. The final result is also the same, whether typhoid, dysentery or cholera germs are spread by the fingers of a carrier or by the feet of a fly. But the subject of insect carriers, while closely related to that of human carriers, practically, deserves separate consideration theoretically.

From the biological point of view, as has already been pointed out, the chronic carrier state must be considered as the result of a drawn battle between mankind and its parasites. It is personal victory as the invader is restricted to an insignificant position; it is a social defeat, however, as the invader still maintains a foothold and is able to attack new individuals. In other words, chronic carriers are examples of the balance which nature tends to establish in the struggle for existence. The same carrier balance is seen in the whole scale of life from the lowest to the highest forms. Whether in plants, animals or man, parasites are competing with hosts in the infectious diseases and the carrier state is one end result. Neither side wins a complete victory.

The situation is compromised and infection and immunity are balanced against each other. While we accredit nature with marvellous adaptations for the welfare of mankind, it should not be forgotten that a typhoid gall bladder or a diphtheria tonsil represent a diabolical mechanism for the perpetuation of some of man's real enemies. It is the aim of preventive medicine to break up this balance in favour of man.

Work on carriers is another evidence of, and argument for, the socialization of medicine. The extreme individualism of the past is very satisfactory to the favored few, but it does not take into consideration the welfare of the many who make up the strength of the nation and who have a way of getting what they want and need. The care of the individual case is a unit of medical attention, but it is only part of an adequate program for the control of infectious diseases. The carrier is also a problem which requires special handling, technical and administrative. In addition to diagnosing and treating the case, physicians should learn to diagnose and treat the carrier and keep pace with the increasing social demands for the application of practical measures. As physicians and citizens we need to realize, once for all, that while in some respects the individual is an ultimate unit, in others, he is only a part of higher units, the family, the community, and the nation, and he cannot exist without them. Hence, medically as well as biologically, the interests of the whole, that is, of the race, are greater than those of the individual parts. On the other hand, it is the individual who, in the long run, profits from the welfare of the group.

Sacquepee, E. : Les Porteurs de germes. Bulletin de L'Institut Pasteur, 1910, 8, 1, 321, 689.

Ledingham and Arkwright: The Carrier Problem in the Infectious Diseases. 1912, Edward Arnold, London.

Simon, C. E. : Human Infection Carriers. 1919, Lea and Febiger, Philadelphia and New York.

Craig, C. F.: Jour. Amer. Med. Assoc, 1921, lxxvii, 827.

CHAPTER I Impoktance

The importance of carriers is two fold. In the first place, chronic carriers constitute more or less permanent reservoirs of pathogenic microorganisms. Cases are usually acute and the danger of spread of infection is limited to days. The chronic carrier, however, is able to infect his environment or contacts for months or years. While the acute case excretes more germs and probably causes most cases after an epidemic starts, the carrier is able to start the epidemic itself by storing the germs until seasonal or other conditions are favorable for an outbreak. Some workers claim that in this way a carrier will always be found as a connecting link in any considerable series of cases. According to Vaughan, one of the principal contributions of bacteriology to epidemiology is the teaching about carriers.

Soon after the recognition of the infectious nature of many diseases, it was thought that the environment of cases was heavily contaminated with germs. In this period efforts were directed especially at the disinfection of water, milk, clothing, and fomites. It was soon learned, however, that many pathogenic germs live outside the hosts only a short time and that, while much can be done by sanitation, the contact avenue of infection remains largely open. Attention was then focused on the case itself. It was taught that if all acute cases were detected early and isolated the streams of disease would dry up. But again it was soon found that, while much can be done along these lines, there is still a good sized flow from the carrier reservoir. At present, therefore, much attention is being devoted to this other personal source of infection.

The second reason why carriers are important in preventive medicine is, of course, the fact that they are apparently and practically healthy. The case, confined to bed or to a sick room, limits the spread of parasites, consciously or unconsciously. The carrier, however, usually unaware of his condition, moves about freely, infecting his environment or contacts without notice. It is this circumstance which has made the subject so dramatic to the laity and so serious to the profession.

The importance of carriers varies in different diseases. In a few instances, such as typhoid, enough information is becoming available to actually estimate the number of cases due to carriers as compared with those due to other cases. In other diseases the exact relative importance of carriers is not so well known, but the carrier has a definite place in the epidemiology of cholera, dysentery, diphtheria, cerebrospinal meningitis and malaria. The organisms can be identified and traced. In some diseases, such as smallpox and measles, carriers are not important, according to usual statements. This position is based on epidemiological evidence which may or may not have been rightly interpreted. Until more is known about the organisms causing many diseases, no adequate statements can be made about their carrier aspects.

There is undoubtedly a tendency at times to overestimate the importance of carriers. Other cases, including mild ones, should be considered as a cause of a given case before a carrier is suspected. It should also be remembered that many so-called carriers are really pseudo-carriers who are simply parasitized by non-virulent organisms. Those organisms may resemble pathogenes morphologically and a presumptive diagnosis may be made. But virulence tests nearly always show that some suspected organisms have no significance. Hence, while recognizing the real importance of the true carrier as a reservoir of pathogenic parasites and as an unadvertized danger, the practitioner of preventive medicine must recognize the relative importance of carriers in different diseases and the existence of the pseudo-carrier.

On the other hand, there is in some quarters a tendency to belittle the carrier program as ineffective. This tendency, I believe, is a mistaken one. It is based simply on our insufficient knowledge or inadequate control. We should not give up the advantage won by the known existence of carriers of pathogenic organisms because we cannot always assign them a definite place in the unknown whirl of atoms or control their activities. It should be realized that only rarely has the carrier plan of attack on an infectious disease been given a thorough trial. A certain amount of work has been done, but it is usually not complete and

IMPORTANCE 23

radical because of the limitation of facilities and control. The plan breaks down because the work is too extensive. This circumstance has lead some workers to minimize the program. It is impossible, however, to sucessfully attack the principles of phorology. The only question is how far the details should be carried out. As laboratory facilities become more numerous and reliable, and as scientific control of events becomes more established, the proper amount of attention will be given to this rational plan of attack on our competitors in life.

The importance of carriers can be realized by considering, first, the percentage of cases which become convalescent carriers, then the percentage of contacts who become contact carriers and then the percentage of both kinds of carriers in the general population. Best of all, however, is the actual demonstration of the spread of organisms by a carrier in a specific group of cases.

The study of carriers is valuable to the medical student as it shows him something of the biological background of disease which has been so useful in orienting the medical sciences. Carriers form a link in the natural history of disease. To understand them is to acquire a liberal medical education and to control them is to aid in defending and extending civilization. The different phases of carrier work involve anatomy, physiology, bacteriology, parasitology, pathology, immunology, medicine, surgery, sanitation, hospitalization, quarantine and follow up service.

The general practitioner needs to know the best teaching about carriers as he is in the most strategic position to break up the parasitic balance in favor of man. Too often, either through ignorance or limited view of responsibility, this opportunity is lost. Patients are carried through a severe infection with skill, but are turned loose, without release cultures, to inflict the same disease on others. By insisting on release examinations in any case whose cause can be found by such examinations, the practitioner can have the satisfaction of practising preventive medicine at the most critical period. If the examination is negative, the case can be completely closed and the patient is better satisfied. If the examination is positive, the patient may be a temporary convalescent carrier and may clear up with a short extension of convalescence. If the case becomes a chronic carrier, he can in some instances be cured and at least he can be instructed in personal hygiene. If he does not respond to social obligations, restrictive measures must be applied. In diphtheria, this ground is already covered by regulations, but in several other diseases the practitioner decides what shall or shall not be done. It is much easier to ignore this subject, but microorganisms can not be trusted. There will be no general advance in the prevention of many diseases until the general practitioner helps by detecting and handling convalescent carriers.

Most of all the public health official must realize the importance of carriers as his position is due to a social demand for supervision of the health of groups, among whom carriers are sure to be found. He must officially be in position to diagnose and handle carriers. Carrier work among private physicians is largely voluntary and depends on the degree of social consciousness of the individual. The public health official, however, is paid to be socially minded.

The organization includes, first, the laboratory for the discovery of carriers, and second, regulations to secure appropriate action. The needs of the laboratory are more fully discussed under the heading of diagnosis. It is sufficient to say here that nowhere can the laboratory facilities be considered adequate for the work that might be done. Of course the question is an economic and social one. Do the results justify the expense and trouble? The answer here as elsewhere seems to be that, as scientific knowledge increases, there is an increasing demand for its application in the amelioration of human life.

On the administrative side, there are many perplexing questions of policy in handling carriers. The uncertainty of our knowledge in some diseases and the fallability of laboratory workers often add to the confusion. But one point should be kept clear. The interests of the group of race are supreme over those of the individual. This decision has been handed down by Nature and by Society and other decisions must conform. The interference with the individual should be as slight as possible, but there should be no question about the principle that governs.

Vaughan, V. C: Epidemiology and Public Health. 1922, C. V. Mosby

& Co., St. Louis.

Conklin, E. G. : The Direction of Human Evolution. 1921, Charles

Scribners Sons, New York.

CHAPTER II Pathology

The pathology of carriers includes specific lesions and a general or local immunity. The anatomical basis is an important factor, but immune reactions underlie the phenomenon as a whole. While there are many unknown elements in the equilibrium between host and parasite as seen in carriers, there is also available much actual knowledge or suggestive information.

In the temporary contact carrier there is probably no demonstrable lesion. The organisms apparently live and multiply for a short time on mucous surfaces and then die off or are washed away by the secretions. The tissues are immune and in the absence of actual proof the most that can be imagined is a slight preexisting lesion which produces an increased secretion of mucus as a temporary focus.