CHAPTER XI. Some Possible, but Imperfectly Established Cases of Arthropod

SOME POSSIBLE, BUT IMPERFECTLY ESTABLISHED CASES OF ARTHROPOD TRANSMISSION OF DISEASE

INFANTILE PARALYSIS OR ACUTE ANTERIOR POLIOMYELITIS

The disease usually known in this country as infantile paralysis or, more technically, as acute anterior poliomyelitis, is one which has aroused much attention in recent years.

The causative organism of infantile paralysis is unknown, but it has been demonstrated that it belongs to the group of filterable viruses. It gives rise to a general infection, producing characteristic lesions in the central nervous system. The result of the injury to the motor nerves is a more or less complete paralysis of the corresponding muscle. This usually manifests itself in the legs and arms. The fatal cases are usually the result of paralysis of the muscles of respiration. Of the non-fatal cases about 60 per cent remain permanently crippled in varying degrees.

Though long known, it was not until about 1890 that it was emphasized that the disease occurs in epidemic form. At this time Medin reported his observations on an epidemic of forty-three cases which occurred in and around Stockholm in 1887. Since then, according to Frost (1911), epidemics have been observed with increasing frequency in various parts of the world. The largest recorded epidemics have been those in Vermont, 1894, 126 cases; Norway and Sweden, 1905, about 1,500 cases; New York City, 1907, about 2,500 cases. Since 1907 many epidemics have been reported in the United States, and especially in the Northern States east of the Dakotas. In 1912 there were over 300 cases of the disease in Buffalo, N. Y., with a mortality of somewhat over 11 per cent.

In view of the sudden prominence and the alarming spread of infantile paralysis, there have been many attempts to determine the cause, and the manner in which the disease spreads and develops in epidemic form. In the course of these studies, the question of possible transmission by insects was naturally suggested.

C. W. Howard and Clark (1912) presented the results of studies in this phase of the subject. They dealt especially with the house-fly, bedbug, head, and body lice, and mosquitoes. It was found that the house-fly (Musca domestica) can carry the virus of poliomyelitis in an active state for several days upon the surface of the body and for several hours within the gastro-intestinal tract. Mosquitoes and lice were found not to take up or maintain the virus. On the other hand, the bedbug (Cimex lectularius) was found to take the virus from the infected monkeys and to maintain it in a living state within the body for a period of seven days. This was demonstrated by grinding up in salt solution, insects which had fed on poliomyelitic animals and injecting the filtrate into a healthy monkey. The experimenters doubted that the bedbug is a carrier of the virus in nature.

Earlier in the same year, Brues and Sheppard published the results of an intensive epidemiological study of the outbreak of 1911, in Massachusetts. Special attention had been paid to the possibility of insect transfer and the following conclusion was reached:

"Field work during the past summer together with a consideration of the epidemiology of the disease so far as known, points strongly toward biting flies as possible carriers of the virus. It seems probable that the common stable-fly (Stomoxys calcitrans L.) may be responsible to a certain extent for the spread of acute epidemic poliomyelitis, possibly aided by other biting flies, such as Tabanus lineola. No facts which disprove such a hypothesis have as yet been adduced, and experiments based upon it are now in progress."

As stated by Brues (1913), especial suspicion fell upon the stable-fly because:

1. The blood-sucking habits of the adult fly suit it for the transfer of virus present in the blood.

2. The seasonal abundance of the fly is very closely correlated with the incidence of the disease, rising rapidly during the summer and reaching a maximum in July and August, then slowly declining in September and October.

3. The geographical distribution of the fly is, so far as can be ascertained, wider, or at least co-extensive with that of poliomyelitis.

4. Stomoxys is distinctly more abundant under rural conditions, than in cities and thickly populated areas.

5. While the disease spreads over districts quickly and in a rather erratic way, it often appears to follow along lines of travel, and it is known that Stomoxys flies will often follow horses for long distances along highways.

6. In a surprisingly large number of cases, it appeared probable that the children affected had been in the habit of frequenting places where Stomoxys is particularly abundant, i.e., about stables, barnyards, etc.

The experiments referred to were carried on during the summer of 1912 and in September Dr. Rosenau announced that the disease was transferred by the bite of the stable-fly.

A monkey infected by inoculation was exposed to the bites of upwards of a thousand of the Stomoxys flies daily, by stretching it at full length and rolling it in a piece of chicken wire, and then placing it on the floor of the cage in which the flies were confined. The flies fed freely from the first, as well as later, after paralysis had set in. Alternating with the inoculated monkey, healthy monkeys were similarly introduced into the cage at intervals. New monkeys were inoculated to keep a supply of such infected animals and additional healthy ones were exposed to the flies, which fed willingly and in considerable numbers on each occasion. "Thus the flies were given every opportunity to obtain infection from the monkeys, since the animals were bitten during practically every stage of the disease from the time of the inoculation of the virus till their death following the appearance of paralysis. By the same arrangement the healthy monkeys were likely to be bitten by flies that had previously fed during the various stages of the disease on the infected monkeys. The flies had meanwhile enjoyed the opportunity of incubating the virus for periods varying from the day or two which usually elapses between consecutive feedings, to the two or three-week period for which at least some (although a very small percentage) of the flies lived in the cage."

"In all, twelve apparently healthy monkeys of a small Japan species were exposed to the flies in the manner described for the infected monkeys. Some were placed in the cage only once or twice and others a number of times after varying intervals. These exposures usually lasted for about half an hour, but were sometimes more protracted. No results were apparent until two or three weeks after the experiment was well under way, and then in rather rapid succession six of the animals developed symptoms of poliomyelitis. In three, the disease appeared in a virulent form, resulting in death, while the other three experienced transient tremblings, diarrhoea, partial paralysis and recovery."--Brues, 1913.

Very soon after the announcement of the results of experiments by Rosenau and Brues, they were apparently conclusively confirmed by Anderson and Frost (1912), who repeated the experiments, at Washington. They announced that through the bites of the Stomoxys flies that had previously fed on infected monkeys, they had succeeded in experimentally infecting three healthy monkeys.

The results of these experiments gained much publicity and in spite of the conservative manner in which they had been announced, it was widely proclaimed that infantile paralysis was conveyed in nature by the stable-fly and by it alone.

Serious doubt was cast on this theory by the results of further experiments by Anderson and Frost, reported in May of 1913. Contrary to the expectations justified by their first experience, the results of all the later, and more extended, experiments were wholly negative. Not once were these investigators again able to transmit the infection of poliomyelitis through Stomoxys. They concluded that it was extremely doubtful that the insect was an important factor in the natural transmission of the disease, not only because of their series of negative results, "but also because recent experiments have afforded additional evidence of the direct transmissibility or contagiousness of poliomyelitis, and because epidemiological studies appear to us to indicate that the disease is more likely transmitted largely through passive human virus carriers."

Soon after this, Kling and Levaditi (1913) published their detailed studies on acute anterior poliomyelitis. They considered that the experiments of Flexner and Clark (and Howard and Clark), who fed house-flies on emulsion of infected spinal cord, were under conditions so different from what could occur in nature that one could not draw precise conclusions from them regarding the epidemiology of the disease. They cited the experiments of Josefson (1912), as being under more reasonable conditions. He sought to determine whether the inoculation of monkeys with flies caught in the wards of the Hospital for Contagious Diseases at Stockholm, where they had been in contact with cases of poliomyelitis, would produce the disease. The results were completely negative.

Kling and Lavaditi made four attempts of this kind. The flies were collected in places where poliomyelitics had dwelt, three, four and twenty-four after the beginning of the disease in the family and one, three, and fifteen days after the patient had left the house. These insects were for the greater part living and had certainly been in contact with the infected person. In addition, flies were used which had been caught in the wards of the Hospital for Contagious Diseases at Soderkoping, when numbers of poliomyelitics were confined there. Finally, to make the conditions as favorable as possible, the emulsions prepared from these flies were injected without previous filtering, since filtration often causes a weakening of the virus. In spite of these precautions, all their results were negative, none of the inoculated animals having contracted poliomyelitis. They also experimented with bedbugs which had fed upon infected patients at various stages of the disease, but the results in these cases also were wholly negative.

Kling and Levaditi considered at length the possibility of transmission of the disease by Stomoxys. As a result of their epidemiological studies, they found that infantile paralysis continued to spread in epidemic form in the dead of winter, when these flies were very rare and torpid, or were even completely absent. Numerous cases developed in the northern part of Sweden late in October and November, long after snow had fallen. On account of the rarity of the Stomoxys flies during the period of their investigations they were unable to conduct satisfactory experiments. In one instance, during a severe epidemic, they found a number of the flies in a stable near a house inhabited by an infected family, though none was found in the house itself. These flies were used in preparing an emulsion which, after filtering, was injected into the peritoneal cavity of a monkey. The result was wholly negative.

As for the earlier experiments, Kling and Levaditi believe if the flies were responsible for the transmission of the disease in the cases reported by Rosenau and Brues, and the first experiments of Anderson and Frost, it was because the virus of infantile paralysis is eliminated with the nasal secretions of paralyzed monkeys and the flies, becoming contaminated, had merely acted as accidental carriers.

Still further evidence against the hypothesis of the transmission of acute anterior poliomyelitis by Stomoxys calcitrans was brought forward by Sawyer and Herms (1913). Special precautions were used to prevent the transference of saliva or other possibly infectious material from the surface of one monkey to that of another, and to avoid the possibility of complicating the experiments by introducing other pathogenic organisms from wild flies, only laboratory-bred flies were used. In a series of seven carefully performed experiments, in which the conditions were varied, Sawyer and Herms were unable to transmit poliomyelitis from monkey to monkey through the agency of Stomoxys, or to obtain any indication that the fly is the usual agent for spreading the disease in nature.

The evidence at hand to date indicates that acute anterior poliomyelitis, or infantile paralysis, is transmitted by contact with infected persons. Under certain conditions insects may be agents in spreading the disease, but their role is a subordinate one.

Pellagra

PELLAGRA is an endemic and epidemic disease characterized by a peculiar eruption or erythema of the skin (figs 144 and 145), digestive disturbances and nervous trouble. Insanity is a common result, rather than a precursor of the disease. The manifestations of pellagra are periodic and its duration indeterminate.

The disease is one the very name of which was almost unknown in the United States until within the past decade. It has usually been regarded as tropical, though it occurs commonly in Italy and in various parts of Europe. Now it is known that it not only occurs quite generally in the United States but that it is spreading. Lavinder (1911) says that "There are certainly many thousand cases of the disease in this country, and the present situation must be looked upon with grave concern."

It is not within the scope of this book to undertake a general discussion of pellagra. The subject is of such importance to every medical man that we cannot do better than refer to Lavinder's valuable precis. We can only touch briefly upon the entomological phases of the problems presented.

The most commonly accepted theories regarding the etiology of the disease have attributed it to the use of Indian corn as an article of diet. This supposed relationship was explained either on the basis of, (a) insufficiency of nutriment and inappropriateness of corn as a prime article of food; (b) toxicity of corn or, (c) parasitism of certain organisms--fungi or bacteria--ingested with either sound or deteriorated corn.

In 1905, Sambon proposed the theory of the protozoal origin of pellagra and in 1910 he marshalled an imposing array of objections to the theory that there existed any relationship between corn and the disease. He presented clear evidence that pellagra existed in Europe before the introduction of Indian corn from America, as an article of diet, and that its spread was not pari passu with that of the use of corn. Cases were found in which the patients had apparently never used corn, though that is obviously difficult to establish. He showed that preventive measures based on the theory had been a failure. Finally, he believed that the recurrence of symptoms of the disease for successive springs, in patients who abstained absolutely from the use of corn, militated against the theory.

On the other hand, Sambon believed that the periodicity of the symptoms, peculiarities of distribution and seasonal incidence, and analogies of the symptoms to those of other parasitic diseases indicated that pellagra was of protozoal origin, and that it was insect-borne.

The insect carriers, he believed to be one or more species of Simuliidae, or black-flies. In support of this he stated that Simulium appears to effect the same topographical conditions as pellagra, that in its imago stage it seems to present the same seasonal incidence, that it has a wide geographical distribution which seems to cover that of pellagra, and that species of the genus are known to cause severe epizootics. Concluding from his studies in Italy, that pellagra was limited almost wholly to agricultural laborers, he pointed out that the Simulium flies are found only in rural districts, and as a rule do not enter towns, villages, or houses.

When Sambon's detailed report was published in 1910, his theory was seized upon everywhere by workers who were anxious to test it and who, in most cases, were favorably disposed towards it because of the wonderful progress which had been made in the understanding of other insect-borne diseases. In this country, the entomological aspects of the subject have been dealt with especially by Forbes (1912), and by King and Jennings, under the direction of W. D. Hunter, of the Bureau of Entomology, and in cooperation with the Thompson-McFadden Pellagra Commission of the Department of Tropical Medicine of the New York Post-Graduate Medical School. An important series of experiments with monkeys has been undertaken by S. J. Hunter, of Kansas, but unfortunately we have as yet no satisfactory evidence that these animals are susceptible to the disease--a fact which renders the whole problem difficult.

The accumulated evidence is increasingly opposed to Sambon's hypothesis of the transmission of pellagra by Simulium. This has been so clearly manifested in the work of the Thompson-McFadden Commission that we quote here from the report by Jennings (1914):

"Our studies in 1912 convinced us that there was little evidence to support the incrimination of any species of Simulium in South Carolina in the transmission of pellagra. Reviewing the group as a whole, we find that its species are essentially "wild" and lack those habits of intimate association with man which would be expected in the vector of such a disease as pellagra. Although these flies are excessively abundant in some parts of their range and are moderately so in Spartanburg County, man is merely an incidental host, and no disposition whatever to seek him out or to invade his domicile seems to be manifested. Critically considered, it is nearer the fact that usually man is attacked only when he invades their habitat."

"As our knowledge of pellagra accumulates, it is more and more evident that its origin is in some way closely associated with the domicile. The possibility that an insect whose association with man and his immediate environment is, at the best, casual and desultory, can be active in the causation of the disease becomes increasingly remote."

"Our knowledge of the biting habits of Simulium is not complete, but it is evident, as regards American species at least, that these are sometimes not constant for the same species in different localities. Certain species will bite man freely when opportunity offers, while others have never been known to attack him. To assume that the proximity of a Simulium-breeding stream necessarily implies that persons in its vicinity must be attacked and bitten is highly fallacious. In Spartanburg County attacks by Simulium seems to be confined to the immediate vicinity of the breeding-places. Our records and observations, exceedingly few in number, refer almost exclusively to such locations. Statements regarding such attacks, secured with much care and discrimination from a large number of persons, including many pellagrins, indicate conclusively that these insects are seldom a pest of man in this county. A certain number of the persons questioned were familiar with the gnats in other localities, but the majority were seemingly ignorant of the existence of such flies with biting habits. This is especially striking, in view of the fact that the average distance of streams from the homes of the pellagra cases studied was about 200 yards, many being at a distance of less than 200 yards, and that 78 per cent of these streams were found to be infested by larval Simulium. Such ignorance in a large number of persons cannot be overlooked and indicates strongly that our belief in the negligible character of local attacks by Simulium is well founded."

"In localities infested by 'sand-flies,' mosquitoes, etc., these pests are always well known and the ignorance described above is very significant."

"Such positive reports as we received nearly always referred to bites received in the open, along streams, etc., and observations made of their attack were of those on field laborers in similar situations. Males engaged in agricultural pursuits are almost exempt from pellagra in Spartanburg County. During the season of 1913, in some two or three instances, observations were made of the biting of Simulium and some additional and entirely creditable reports were received. These observations and reports were under conditions identical with those referred to in the reports of 1912 and confirm the conclusions based on the observations of that year. I would repeat with emphasis that it is inconceivable that a fly of the appearance and habits of the prevalent species of Simulium could be present in such a region, especially about the haunts of man and attack him with sufficient frequency and regularity to satisfactorily account for so active and prevalent a disease as pellagra without being a well-known and recognized pest."

"In connection with the conditions in the Piedmont region of South Carolina, it may be well to cite the results of a study of those in the arid region of western Texas."

"In May, 1913, in company with Capt. J. F. Siler of the Thompson-McFadden Pellagra Commission, I visited the region of which Midland in Midland County is the center. This region is very dry and totally devoid of running water for a long distance in every direction. The only natural source of water-supply, a few water holes and ponds, were visited and found to be of such a nature that the survival of Simulium, far less its propagation in them, is absolutely impossible. The nearest stream affording possibilities as a source of Simulium is 60 miles away, while the average distance of such possibility is not less than 100 miles."

"Artificial sources of water-supply were also investigated carefully and were found to offer no opportunity for the breeding of Simulium."

"At Midland the histories of five cases of pellagra were obtained, which gave clear evidence that this place or its immediate vicinity was the point of origin. Persons of long residence in the country were questioned as to the occurrence of such flies as Simulium and returned negative answers. These included a retired cattle owner, who is a man of education and a keen observer, an expert veterinarian stationed in the country who has the cattle of the country under constant observation, and a practical cattle man, manager of a ranch and of wide experience. The latter had had experience with 'Buffalo gnats' in other localities (in the East) and is well acquainted with them. His close personal supervision of the cattle under his charge, makes it practically certain that he would have discovered these gnats had they been present in the country."

"At the time the study was made, Simulium was breeding and active in the adult state in the vicinity of Dallas, Texas, in the eastern part of the state. We have here a region in which cases of pellagra have originated, yet in which Simulium does not and cannot breed."

Other possible insect vectors of pellagra have been studied in great detail and the available evidence indicates that if any insect plays a role in the spread of the disease, Stomoxys calcitrans most nearly fills the conditions. This conclusion was announced by Jennings and King in 1912, and has been supported by their subsequent work.

Yet, after all the studies of the past decade, the old belief that pellagra is essentially of dietary origin is gaining ground. Goldberger, Waring and Willets (1914) of the United States Public Health Service summarize their conclusions in the statement, (1) that it is dependent on some yet undetermined fault in a diet in which the animal or leguminous protein component is disproportionately large and (2) that no pellagra develops in those who consume a mixed, well-balanced, and varied diet, such, for example, as that furnished by the Government to the enlisted men of the Army, Navy, and Marine Corps.

Leprosy

LEPROSY is a specific, infectious disease due to Bacillus leprae, and characterized by the formation of tubercular nodules, ulcerations, and disturbances of sensation. In spite of the long time that the disease has been known and the dread with which it is regarded, little is known concerning the method of transfer of the causative organism or the means by which it gains access to the human body.

It is known that the bacilli are to be found in the tubercles, the scurf of the skin, nasal secretions, the sputum and, in fact in practically all the discharges of the leper. Under such conditions it is quite conceivable that they may be transferred in some instances from diseased to healthy individuals through the agency of insects and other arthropods. Many attempts have been made to demonstrate this method of spread of the disease, but with little success.

Of the suggested insect carriers none seem to meet the conditions better than mosquitoes, and there are many suggestions in literature that these insects play an important role in the transmission of leprosy. The literature has been reviewed and important experimental evidence presented by Currie (1910). He found that mosquitoes feeding, under natural conditions, upon cases of nodular leprosy so rarely, if ever, imbibe the lepra bacillus that they cannot be regarded as one of the ordinary means of transference of this bacillus from lepers to the skin of healthy persons. He believes that the reason that mosquitoes that have fed on lepers do not contain the lepra bacillus is that when these insects feed they insert their proboscis directly into a blood vessel and thus obtain bacilli-free blood, unmixed with lymph.

The same worker undertook to determine whether flies are able to transmit leprosy. He experimented with five species found in Honolulu,--Musca domestica, Sarcophaga pallinervis, Sarcophaga barbata, Volucella obesa and an undetermined species of Lucilia. The experiments with Musca domestica were the most detailed. From these experiments he concluded, first, that all of the above-named flies, when given an opportunity to feed upon leprous fluids, will contain the bacilli in their intestinal tracts and feces for several days after such feeding. Second, that considering the habits of these flies, and especially those of Musca domestica, it is certain that, given an exposed leprous ulcer, these insects will frequently convey immense numbers of lepra bacilli, directly or indirectly, to the skins, nasal mucosa, and digestive tracts of healthy persons. Additional evidence along this line has recently been brought forward by Honeij and Parker (1914), who incriminate both Musca domestica and Stomoxys calcitrans. Whether or not such insect-borne bacilli are capable of infecting persons whose skin and mucosa are thus contaminated, Currie was unwilling to maintain, but he concludes that until we have more accurate knowledge on this point, we are justified in regarding these insects with grave suspicion of being one of the means of disseminating leprous infection.

Various students of the subject have suggested that bed-bugs may be the carriers of leprosy and have determined the presence of acid-fast bacilli in the intestines of bed-bugs which had fed on leprous patients. Opposed to this, the careful experiments of Thompson (1913) and of Skelton and Parkham (1913) have been wholly negative.

Borrel has recently suggested that Demodex, may play a role in spreading the infection in families. Many other insects and acariens have been suggested as possible vectors, but the experimental data are few and in no wise conclusive. The most that can be said is that it is quite possible that under favorable conditions the infection might be spread by any of the several blood-sucking forms or by house-flies.

Verruga peruviana

VERRUGA PERUVIANA is defined by Castellani and Chalmers as "a chronic, endemic, specific, general disorder of unknown origin, not contagious, but apparently inoculable, and characterized by an irregular fever associated with rheumatoid pains, anemia, followed by granulomatous swellings in the skin, mucous membranes, and organs of the body." It has been generally believed by medical men interested that the comparatively benign eruptive verruga is identical with the so-called Oroya, or Carrion's fever, a malignant type. This view is not supported by the work of Strong, Tyzzer and Brues, (1913).

The disease is confined to South America and to definitely limited areas of those countries in which it does occur. It is especially prevalent in some parts of Peru.

The causative organism and the method of transfer of verruga are unknown. Castellani and Chalmers pointed out in 1910 that the study of the distribution of the disease in Peru would impress one with the similarity to the distribution of the Rocky Mountain fever and would lead to the conclusion that the aetiological cause must in some way be associated with some blood-sucking animal, perhaps an arachnid, and that this is supported by the fact that the persons most prone to the infection are those who work in the fields.

More recently, Townsend (1913), in a series of papers, has maintained that verruga and Carrion's disease are identical, and that they are transmitted to man by the bites of the Psychodid fly, Phlebotomus verrucarum. He succeeded in producing the eruptive type of the disease in experimental animals by injecting a physiological salt trituration of wild Phlebotomus flies. A cebus monkey was exposed from October so to November 6, by chaining him to a tree in the verruga zone, next to a stone wall from which the flies emerged in large numbers every night. Miliar eruption began to appear on the orbits November 13 and by November 21, there were a number of typical eruptions, with exudation on various parts of the body exactly like miliar eruptive sores commonly seen on legs of human cases.

An assistant in the verruga work, George E. Nicholson, contracted the eruptive type of the disease, apparently as a result of being bitten by the Phlebotomus flies. He had slept in a verruga zone, under a tight net. During the night he evidently put his hands in contact with the net, for in the morning there were fifty-five unmistakable Phlebotomus bites on the backs of his hands and wrists.

Townsend believes that in nature, lizards constitute the reservoir of the disease and that it is from them that the Phlebotomus flies receive the infection.

Cancer

There are not wanting suggestions that this dread disease is carried, or even caused, by arthropods. Borrel (1909) stated that he had found mites of the genus Demodex in carcinoma of the face and of the mammae. He believed that they acted as carriers of the virus.

Saul (1910) and Dahl (1910) go much further, since they attribute the production of the malignant growth to the presence of mites which Saul had found in cancers. These Dahl described as belonging to a new species, which he designated Tarsonemus hominis. These findings have since been confirmed by several workers. Nevertheless, the presence of the mite is so rare that it cannot be regarded as an important factor in the causation of the disease. The theory that cancer is caused by an external parasite is given little credence by investigators in this field.

IN CONCLUSION, it should be noted that the medical and entomological literature of the past few years abounds in suggestions, and in unsupported direct statements that various other diseases are insect-borne. Knab (1912) has well said "Since the discovery that certain blood-sucking insects are the secondary hosts of pathogenic parasites, nearly every insect that sucks blood, whether habitually or occasionally, has been suspected or considered a possible transmitter of disease. No thought seems to have been given to the conditions and the characteristics of the individual species of blood-sucking insects, which make disease transmission possible."

He points out that "in order to be a potential transmitter of human blood-parasites, an insect must be closely associated with man and normally have opportunity to suck his blood repeatedly. It is not sufficient that occasional specimens bite man, as, for example, is the case with forest mosquitoes. Although a person may be bitten by a large number of such mosquitoes, the chances that any of these mosquitoes survive to develop the parasites in question, (assuming such development to be possible), and then find opportunity to bite and infect another person, are altogether too remote. Applying this criterion, not only the majority of mosquitoes but many other blood-sucking insects, such as Tabanidae and Simuliidae, may be confidently eliminated. Moreover, these insects are mostly in evidence only during a brief season, so that we have an additional difficulty of a very long interval during which there could be no propagation of the disease in question." He makes an exception of tick-borne diseases, where the parasites are directly transmitted from the tick host to its offspring and where, for this reason, the insect remains a potential transmitter for a very long period. He also cites the trypanosome diseases as possible exceptions, since the causative organisms apparently thrive in a number of different vertebrate hosts and may be transmitted from cattle, or wild animals, to man.

Knab's article should serve a valuable end in checking irresponsible theorizing on the subject of insect transmission of disease. Nevertheless, the principles which he laid down cannot be applied to the cases of accidental carriage of bacterial diseases, or to those of direct inoculation of pyogenic organisms, or of blood parasites such as the bacillus of anthrax, or of bubonic plague. Accumulated evidence has justified the conclusion that certain trypanosomes pathogenic to man are harbored by wild mammals, and so form an exception. Townsend believes that lizards constitute the natural reservoir of verruga; and it seems probable that field mice harbor the organism of tsutsugamushi disease. Such instances are likely to accumulate as our knowledge of the relation of arthropods to disease broadens.