CHAPTER XII
RELAPSING FEVER
Synonyms.—— Febris recurrens; spirillum fever; famine fever; tick fever.
Definition.—— An acute infectious disease, or, possibly, a group of infectious diseases, characterized by fever of sudden onset and, after several days (one to seven), rapid subsidence, and which may relapse at intervals of from one to seven or more days for an indefinite number of times. It is caused by spirochætes which are present in the blood during the fever and are transmitted by certain insects (bug, body-louse) or by certain ticks (Argas, Ornithodoros).
Geographical distribution.—— Relapsing fever is found in Europe, Asia, Africa, America, and probably in Australasia. In Europe it occurs in Britain and, especially, in Ireland; also in Norway, Denmark, Germany, Russia, and Turkey. In Russia there have been many epidemics; it attacked the Grand Army in the retreat from Moscow, the allied armies in the Crimea, and, also, the armies of both sides in the Russo-Turkish War. In Africa the disease has long been known in Egypt, the Soudan, and Algeria. Recently, Philip Ross, Milne, and Cook found it in Uganda, Dutton and Todd in the Congo Free State, Wellman in Angola, and Koch in German East Africa. In Asia relapsing fever is known to occur in China, in Sumatra, and in India where Carter's classical investigations were made. In America it was recognized in the United States in 1844; in 1809 it was epidemic in New York and Philadelphia. It is probably widely distributed throughout South and Central America.
From the symptoms, as far as they are known, and from the fact that they are communicated by tick bite, we are justified in conjecturing that the carapata disease described by Livingstone and Kirk as endemic in the Zambesi basin, the miana disease of Persia, and a similar disease described by Alleman in Mexico may be spirochæte-produced diseases, and forms of relapsing fever.
History.—— Relapsing fever was known to Hippocrates. He describes an epidemic which he witnessed on the island of Thasos. Among other cases, he quotes those of two brothers, in one of whom the initial paroxysm lasted seven days, in the other six; the intermission in one was five days, in the other six; the relapse in both lasted five days. He further mentions the splenic enlargement, the jaundice, the liability to abortion in pregnant women, and the tendency to menorrhagia. From the time of Hippocrates onwards there is no further notice of relapsing fever in medical literature until 1770; in that year Rutty in his book on the diseases of Dublin described it.
In 1873 Obermeier discovered the spirochsete. In 1897 Tictin stated that the parasite and the disease were communicated by the common bed bug; he infected a monkey with relapsing fever by subcutaneous injection of blood obtained from the stomach of a bug which had previously fed on another monkey inoculated with the disease.
In 1904 Philip Ross and Milne in Uganda, and rather later, but independently, Dutton and Todd on the Congo, discovered that in Africa the spirochsete was communicated by the bite of a tick, Ornithodoros moubata. The last two observers found that the parasite could pass into the egg and larva, and so confer infective powers on the mature tick of the succeeding generation. In 1907 Mackie, in India, recorded an outbreak of relapsing fever in which lice apparently served as the transmitting agent a view favoured by the experiments of Nicolle and others, who further state that the infection can be transmitted hereditarily to the offspring of infected lice.
Etiology.—— Experiments and observation have proved that the various forms of relapsing fever are caused by Spirochceta recurrently or an allied organism Spirochœta recurrentis (S. obermeieri) is a delicate spiral filament (7 to 9 by 0-25 /*) provided, as shown by appropriate staining (Loeffler's whip stain), with a long flagellum (5 to 7 yu by O.1 to 0-2 p). The body of the parasite may have three, four, or six bends or turns, the flagellum from three to five. By the Romanow-sky method the body of the parasite usually stains uniformly, with the exception of the extremities, which are pointed and take only a very faint tint. In fresh blood the spirochsetes, propelled by the flagellum, exhibit very active screw-like movement. Some are longer than others, the long forms resulting from end-to-end attachment of two or more parasites. That this is the explanation of the long forms, which may measure from 16 to 100 u, is shown by staining. In those measuring from 16 to 19 /n we find a flagellum at each end of the filament and a pale zone in the middle, the pale zone corresponding to the approximated lightly staining extremities above referred to. The still longer forms admit of a similar explanation. Although the normal habitat of the spirochætes is the liquor sanguinis, occasionally they are seen in the red blood-corpuscles.
Obermeier and von Jaksch describe certain refractile bodies present in the blood during the fever intermissions. The latter author says that he has observed the development of these bodies into short rods from which the typical spirochætes are eventually evolved. This observation has not been confirmed.
Demonstration of the parasite.—— It is necessary to remember that the parasite only occurs in the blood during the febrile stage of the disease, disappearing from it completely during the non-febrile intervals. In some forms and cases of the disease it is present in large numbers in every field of the microscope; in other forms and cases it is so scanty that many fields have to be examined before a single specimen can be discovered. In thin films of fresh blood its presence can usually be recognized from the agitation its movements communicate to the adjacent corpuscles. In dried and fixed films the stains in general use for malaria work suffice for its demonstration. The indian-ink or Burri method is invaluable for showing up the spirochæte. The technique is as follows: One drop of suspected blood and one drop of indian ink (Pelican brand) are taken up in a platinum loop and mixed together on a slide. The spirochætes appear as white wavy lines on a dark background.
Harrison suggests a modification of this method, substituting a mixture of collargol powder I part, distilled water 19 parts, for the indian ink. The mixture is well shaken up in a black bottle before use. The dark-ground method of illumination is admirably adapted for demonstrating these parasites in a living state. A very strong illuminant preferably a high-power electric light (Nernst lamp), not always procurable in the tropics—— is required.
The " infective granule " of Balfour.—— Balfour has called attention to an interesting phenomenon occurring in the spirochæte infection of fowls, the exact signification of which has not been determined, but which may have reference to the relapses that are so striking a feature in spirochæte infection. His observations have been confirmed by Fantham and others. In spirochæte-infected fowls certain minute highly refractile granules are to be seen in a proportion of the red blood-corpuscles. At one time Balfour considered that these granules resulted from the breaking down of the spirochætes which are frequently observed to enter, move about in, and coil up in the red cells. But by employing the dark-ground method of illumination he was led to conclude that these granules enter the corpuscles as granules, and that they are derived from spirochætes free in the liquor sanguinis. He describes the process of "granule shedding" as follows:——
" By the use of the dark-field method, and more especially by practising liver puncture on chicks at the crisis or on chicks which have been given a sufficiently large dose of salvarsan, I have found that in the liver in particular, also in the spleen and lung, the spirochætes undergo an astonishing change. They discharge from their periplastic sheaths spherical granules, and it is apparently these granules which enter the red cells, develop in them, and complete a cycle of schizogony. The appearance is very remarkable. If a well-infected chick be given a dose of salvaisan, the peripheral blood is soon cleared, or nearly cleared, of spirochætes. If then a drop of liver juice be examined by the dark-field method, it will be found swarming with spirochætes and with highly refractile granules. The source of the latter is soon apparent, for attention will be directed to spirochætes which are not moving in the usual way, but are in a state of violent contortion, or are, so to speak, shaking themselves to and fro. Indeed, I cannot give a more apt comparison than by likening their movements to those of dogs which have been in water and are shaking themselves vigorously to dry their coats. The object of the spirochætes, however, is to rid themselves of the bright, spherical granules which can be seen within them, and which may or may not be aggregations of the so-called chromatin core. These are forced along the periplastic sheath and suddenly discharged, so that they become free in the medium and dance hither and thither as tiny solid, spherical, brilliantly white particles. In process of time the spirochæte loses its activity, becomes difficult to see, and eventually all that is left of it is the limp and lifeless sheath drifting aimlessly in the fluid and liable to be caught up and swept away by some still vigorous parasite. Such a sheath may still retain one or two of the granules which it has been unable to discharge."
Nature of the spirochœte.—— Opinions differ as to the biology of the spirochæte whether it belongs to the bacteria or to the protozoa. Novy and Knapp,* [1] who regard it as a bacterium, point as evidence to (a) the pale zones in the stained long forms as possibly indicating transverse division; (b) the spiral arrangement and very delicate nature of the flagellum, so unlike in these respects that of the flagellata; (c) its not being killed rapidly and disintegrated by the slow addition of water to the blood; (d) its not being provided with an undulating membrane or being attracted, as the trypanosomes are, by air bubbles in microscopic preparations, the trypanosomes in such circumstances arranging themselves around the bubble, their flagella pointing inwards; (e) its uniform staining; (f) absence of nucleus and blepharoplast. In favour of the protozoal nature of the spirochætes are (a) the presence of an undulating membrane but no flagella in certain species, as for example S. plicatilis and S. refringens; (b) the elements constituting a long spiral are all of approximately the same length, which is that of the individual spirochæte; (c) the parasites are not all of the same thickness, some being twice the diameter of others ——facts suggesting a longitudinal, that is protozoal, rather than a transverse or bacterial method of division; (d) the parasite keeps alive for many days—— forty—— in the body of the bug; (e) at least in the case of the African form, it enters the egg of the tick in utero; (f) it is communicated by an arthropod.
Schaudinn propounded the view that the leucocytozoon of the owl (L. ziemanni), after fertilization in the gut of the mosquito, gave rise to an enormous number of trypanosome-like forms which he regarded as spirochætes. .These he considered were a flagellated stage of an intracellular organism and, therefore, belonged to the protozoa. He stated that he had compared his mosquito-bred flagellates with S. recurrentis and S. anserinum, and that he found they agreed completely in morphological character with what he considered the spirochæta stage of L. ziemanni. Before his death Schaudinn seems to have modified his opinion, for in a later paper he states that L. ziemanni is far removed from the typical spirochætes such as S. recurrentis.
Novy and Knapp claim that their observations on the cultivation of trypanosomes in the blood of birds ——which, so far as microscopical examination went, appeared to be free from these organisms—— show that Schaudinn, probably unconsciously, worked with mixed infections; and that the trypanosomes which he regarded as a stage in the life of the intracellular L. ziemanni were not in any way related to the spirochætes, but merely a trypanosome derived either from birds or from trypanosomes of the mosquito, which is itself very liable to this type of infection.
This question of the place in the natural kingdom of the spirochætes of relapsing fever is still undecided. The trend of some recent investigations is to relegate them to the bacteria. Dobell,*[2] as the outcome of improved technique, holds that the argument founded on longitudinal division for regarding them as protozoa is based on imperfect observation; and that the argument based on hereditary transmission through the tick is equally inapplicable, seeing that we now know that a bacterium, B. cuenoti, is hereditarily transmitted by passing into the germ cell of the cockroach. Moreover, Noguchi has succeeded in cultivating two strains of pathogenic spirochætes—S. duttoni and S. obermeieri.
Cultivation.—The successful cultivation of this as of other spirochætes has been performed by Noguchi, and more recently with simplified technique by Hata. For information as to the method, see p. 655. According to Noguchi the organisms multiply by longitudinal division in artificial culture.
Different species, or strains, of relapsing-fever parasites.—Having had the opportunity of examining the blood of a patient from Gibraltar suffering from her eighth paroxysm of relapsing fever, I suggested, on the
Fig. 61.—Spirochæta duttoni.
ground of the unusually large number of relapses and the locality in which the infection was acquired, that there might be several forms of this type of disease, due to different species or varieties of spirochætes. In 1905, in the discussion following the reading of Dutton and Todd's paper on tick fever (Brit. Med. Assn., 1905), Sambon made a similar suggestion, basing it on the wide geographical distribution of relapsing fever, the apparent clinical differences of the disease in different places, and the diversity of animals believed to transmit the infection. Koch pointed out that in African tick fever the febrile stages are shorter (under three days) than in European relapsing fever, and that the spirochætes in the blood are comparatively scanty; similar observations have been made by Philip Ross and Dutton and Todd. Novy and Knapp, in comparing specimens of spirochætes from European and African cases, noted that the spirochætes of the African disease are twice as long (16 μ) as the classical S. recurrentis, and, moreover, that the former has a tendency to dispose itself in figure-of-eight coils or in perfect circles. The Indian species 'they also incline to regard as distinct. The latter, like S. recurrentis, measures about 8 p, but is apparently thinner and more flexible, forming less regular spirals, which, moreover, vary in width. Like the spirochætes of African tick fever, the Indian variety has a tendency to form loops.
For the African form Novy and Knapp propose the name S. duttoni (Fig. 61); S. carteri would be an appropriate name for the Indian form. An Egyptian and an American spirochæte, named respectively S. berbera and S. novyi, have also been described. Such a nomenclature and differentiation can be regarded only as provisional: the evidence as yet is far too limited to warrant its permanent adoption; the recent elaborate experiments of Todd and Breinl have shown that the immunity conferred through infection with the spirochretes of Indian relapsing fever does not protect against the African form, and vice versa, thereby proving that, at least pathologically, they are distinct.
Mode of transmission.—— I have already referred to the Persian disease called miana fever, and to the carapata disease of the Zambesi valley, as forms of relapsing fever. They are certainly communicated by ticks, Argas persicus, or more probably, according to Balfour, by Ornithodoros savignyi in one case, Ornithodoros moubata in the other. Marchoux and Salimbeni were the first to show that a similar disease of fowls caused by the S. gallinarum is transmitted by a tick, the A. miniatus, which Neumann pronounces to be identical with, or a mere variety of, A . persicus. The relapsing fever of Europe has been supposed to be conveyed by the common bed bug, Acanthia lectularia; that of India by lice, possibly by mosquitoes, fleas, and bugs; that of Africa by ticks. Proof of transmission by the bug is by no means complete. Breinl, Kinghorn, and Todd, notwithstanding repeated attempts, failed to communicate the disease by means of these insects. But as we have now reason to believe that there are several strains of pathogenic spirochætes producing disease in man, it may be that these observers have not worked either with the appropriate kind of spirochæte, or with the appropriate species of Acanthia. Thus may we explain the positive results claimed by Sikiel, in Odessa, and by other Russian experimenters. There can be no doubt from the experiments of Philip Ross and Milne in Uganda, of Dutton and Todd on the Congo, and of many others, that the African species, S. duttoni, is normally conveyed by the tick Ornithodoros moubata, and that it can be transmitted not only by the animal that has bitten the infected individual, but by its progeny. The spirochæte has been demonstrated in the egg of the tick by Koch, and Leishman describes certain groups of " coccoid bodies," which may have been derived from spirochætes, in the same situation. It may be in this way that the hereditary transmission of the spirochæte in ticks and lice is effected. According to Leishman the spirochætes are commonly found in ticks' eggs laid in the tropics, but not in those laid in this country; but Balfour believes that these eggs contain his infective granule (see p. 231). Symptoms of a successful infection by the tick appear in from five to seven days.
It would seem that the various insect transmitters act merely in a more or less mechanical way and that there is no essential biological relationship between the parasite and the transmitter, as is the case with the malaria parasite and the mosquito, or with the trypanosome and the tse-tse fly. The spirochæte is abstracted with the blood when the insect transmitter feeds; it multiplies by breaking up into refractile granules*[3] in the gut and Malpighian tubes of the latter as in a culture-tube, and is afterwards passed out with the fæces and deposited on the skin of any human or other warm-blooded victim on which the infected insect may subsequently feed. The irritation caused by the bite of the insect provokes scratching and consequent inoculation of the deposited spirochætes.*[4] The parasite is not introduced by the mouth parts of the insect.
In the case of O. moubata the hereditarily infected nymph can communicate the disease (Nuttall). The tick itself has been shown to be infective up to a year and a half after the initial feed on spirochæte containing blood.
It is undoubtedly the case that in one part of the world the spirochæte of man is transmitted by one species of blood-sucker, and in another part of the world by another species of blood-sucker; that the various relapsing fever spirochætes exhibit slight morphological differences ; that their serum reactions differ; and that the fevers they cause are in some respects different clinically. It is not justifiable, how ever, to conclude on these grounds alone that the various strains of pathogenic spirochætes are specifically distinct. It has been ascertained that as regards some of the strains their usual transmitters are interchangeable. It may well be that the continued passage of a given strain through many generations of the same species of insect transmitter may confer on the spirochæte concerned special morphologic and pathogenic qualities, without at the same time transmuting it specifically. Indeed, it would seem, that opportunity as supplied by the presence of an efficient insect transmitter, the habits and circumstances of the inhabitants, and the introduction of a pathogenic spirochæte are the principal circumstances that determine the endemicity or epidemic prevalence of relapsing fever; and that the insect transmitter has much to do with the pathogenic qualities of the organism that has been cultivated in its alimentary canal for countless generations. Animal experiments.—— It was generally stated that S. recurrentis (S. obermeieri) could be transferred only to man and monkey. Novy and Knapp infected white mice and white rats. The former they found were especially susceptible, the organism appearing in the blood within twenty-four hours of inoculation and persisting to the third day (eighty hours). About this time they disappear for several days from the blood of the infected mice and until the commencement of relapse. The first relapse may be followed by a second, third, or even a fourth, the number varying in individual mice; with each relapse the parasites reappear in the blood. The interval between the relapses, counting from the first appearance of spirochætes in one to their first appearance in the next relapse, is generally about seven days; occasionally it is only two; sometimes it is as long as ten days. The number of spirochætes in the relapses is much smaller than in the first paroxysm, clearly indicating the development of a partial immunity. Recovery in mice, as in other animals, is the rule.
The same observers found rats to be susceptible, but in them the progress of the disease was different. The period of incubation was longer (forty hours), and there were no relapses. As a result of the consecutive passage of the spirochætes through a long series of rats its virulence was augmented, so that the incubation period became reduced to fifteen or eighteen hours, and the persistence of the parasite in the blood prolonged to sixty hours instead of, as originally, forty-eight hours; at the same time the spirochætes became far more abundant.
The parasite, which is present not only in the circulating blood but in all the organs, seems to produce no serious pathological change in the rat beyond great temporary enlargement of the spleen. Recovery is practically invariable. Young rats are more susceptible than old rats. Immunity persists for many months.
Rabbits and guineapigs are refractory.
Immunity.—— Sabritschewsky in 1896 showed that when equal parts of spirochæte-infected blood, or serum, and normal serum are mixed, the spirochætes survive longer than when the infected blood is mixed with that of an individual who has recovered from relapsing fever. He accordingly concluded that the cause of the crisis in relapsing fever and of subsequent immunity was the development of a germicidal substance in the blood. He was the first to apply serum-therapy in the treatment of relapsing fever. He obtained an anti-spirochæte serum by repeated inoculation of the horse with human spirochæte containing blood. The value of this serum was successfully established by Löwenthal; of 87 patients treated, 43 (49 per cent.) recovered without a relapse.
Novy and Knapp have proved the presence of a powerful germicidal substance in relapsing fever blood by comparing the viability of the spirochætes in blood taken (1) at the onset of the disease, (2) during crisis, (3) twelve to twenty-four hours after disappearance of parasites, and (4) from animals hyperimmunized by repeated infection. In the case of the first, the spirochætes live and are mobile for forty days, and the blood will continue infective up to thirty-seven days; in the case of the second, no living spirochætes are to be found after twenty-four to forty-eight hours; in the third, the parasites die in from thirty to sixty minutes; in the last, they are killed instantaneously.
They further showed, by examining the blood during the decline of the fever in an infected animal treated with immune blood, that the presence of agglutinating and germicidal bodies could be demonstrated in vivo from hour to hour. The parasites are seen to form agglutination rosettes and long agglutination filaments of 70 to 100 μ.
Treated in vitro with hyperimmune serum the spirochætes rapidly become unrecognizable aggregations of granules.
Incubation period.— The incubation period usually lasts from two to ten days. In some instances the attack develops promptly on exposure; it is never delayed beyond the fourteenth day. In the artificially inoculated, symptoms show themselves in from two to six days.
Symptoms.— European and Indian type.— The onset is generally abrupt, being marked by chilliness or rigor, giddiness, vomiting, and intense headache. In the young there may be convulsions. Temperature rises rapidly to 104° or 105° F., sometimes even to 108°. The pulse is rapid, 110 to 130. Should fever run high there may be delirium. The skin is dry, although, especially during the first day, occasional sweats may break out. A slight icteric tinting of the conjunctiva is usual; not infrequently jaundice is marked. The spleen is invariably enlarged and tender. The tongue is coated and moist except in bad cases, in which it may become dry and brown. The bowels, as a rule, are confined. Occasionally herpes labialis is noted, and in certain epidemics a rash of rose-coloured spots on the trunk and limbs has been observed. Some authors describe petechise. A slight bronchitis is not uncommon. The urine, not appreciably diminished in amount, is very high-coloured. This, the primary fever, lasts for from five to seven days. At first the morning is usually lower than the evening temperature, but on or about the third day the evening temperature rarely rises above that of the morning. On the fourth, fifth, or sixth day there is again a rise of temperature, sometimes with delirium, ending in crisis of profuse sweating and diarrhoea. The temperature now falls rapidly to normal or subnormal, sometimes dropping in the course of a few hours as much as 10° F. in the latter event, especially in elderly or delicate patients, there may be dangerous collapse.
The initial pyrexia, called first paroxysm, is followed by a first period of apyrexia during which the patient recovers so rapidly that after four or five days it may be difficult to keep him in hospital. But from seven to nine days after the crisis, that is about the fourteenth from the commencement of the attack, rigor again occurs, followed by a second attack of fever first relapse. This may be more severe than the initial paroxysm; usually it is milder and seldom lasts so long. During its continuance the secretion of urine is considerably increased; sweating also is profuse and prostration marked.
With the defervescence of the first relapse the patient enters on the second period of apyrexia, which is usually coincident with convalescence. But in some patients a second relapse may occur, usually about the twenty-first day counting from the commencement of symptoms. This second relapse rarely lasts longer than three days, and is generally milder than the previous paroxysms. In rare instances three, four, five, or even more relapses have been observed. Convalescence may be protracted, and complicated with such sequelæ as nephritis, ophthalmia, otorrhœa, pneumonia, neuritis, parotitis, adenitis. In pregnant women abortion is the rule.
African type.— The African tick-conveyed spirillum fever, although as regards the type of fever resembling the classical European and Indian forms, differs from these in some important particulars. The initial fever is not usually so prolonged, generally terminating in crisis within three days. Diarrhœa and dysenteric symptoms are not uncommon. The apyretic intervals are of very irregular duration, being, according to Philip Ross, sometimes as short as one day, sometimes as long as three weeks; and instead of only one or two relapses, as in ordinary relapsing fever, there may be as many as eleven, five or six relapses being the rule. The fever, though shorter, is as severe in the relapses as in the initial paroxysm, but the intervals tend to become longer. In some instances the reverse is the case, perhaps in both particulars. Sometimes the fever may assume a low chronic form, it may be with severe headache and vomiting. Iritis is not an uncommon complication or sequela. As already stated, the parasites are usually very scanty in peripheral blood and may be hard to find.
In the natives of the endemic districts the disease, as generally observed, is not nearly so severe as in Europeans and strangers, being usually limited to SYNOPTICAL TABLE OF VARIOUS STRAINS OF SPIROCHÆTE AND CLINICAL SYMPTOMS OF THE
RELAPSING FEVERS THEY EVOKE IN MAN
(Compiled mainly from Mackie, Chosky and Balfour)
| Egypt Spirochæta berbera |
Algiers Spirochæta berbera (?) |
Europe Spirochæta recurrentis (obermeieri) |
Africa Spirochæta duttoni |
America Spirochæta novyi |
India Spirochæta carteri |
||
| Minimal length | 13.5 . | 12 . | 12 . | 13 . | 7-9 . | 12 . | |
| Shape | Irregular open flexures. |
Irregular open flexures. |
Spiral. | Open flexures. | Regularly spiral. | Open flexures. | |
| Flagella | ? | ? | Peritrichous. | Peritrichous. | Terminal (Novy.) | ? | |
| Animals Susceptible. | Gerbils, slightly. Monkeys (Cercopithecus). |
Rats and mice, with difficulty. Monkeys (Macacus). |
Small rodents, only after passage through monkeys. |
Small rodents and many animals susceptible. |
Small rodents very susceptible. |
Small rodents infected with difficulty. | |
| Course in animals. | Very mild. | As a rule mild. | Mild. | Very severe. | Severe. | Very mild. | |
| Subinoculations in animals. |
Gerbil to gerbil, positive. |
Rat to rat, or mouse to mouse, with difficulty. |
Monkey to monkey, mouse to mouse, positive. (Fülleborn and Meyer.) |
Monkey to monkey, positive. Same for most animals. (Breinl, Kinghorn & Garrett.) |
Monkey to monkey and mouse to mouse, positive. |
Monkey to monkey and mouse to mouse, positive. (Mackie.) | |
| Course in man. | Fairly severe. First attack 2-8 days; two or three relapses. |
Fairly severe. First attack 2-8 days; two or three relapses. |
One, sometimes two relapses. Incubation period 5-7 days. Duration of attack 5-6 Apyrexia 7-10 |
Severe—four or five relapses. Incubation period 7-10 days. Duration of 1st attack 3 Apyrexia 1-8 |
Mild, rarely more than one relapse. Incubation period 5-7 days. Duration, 1st attack 5-6 Apyrexia 7-10 |
Severe, one or two relapses. Incubation period 7 days. Duration, 1st attack 5-7 Apyrexia 5-13 | |
| Parasites in human blood. |
Variable. | Variable. | Heavy infection. | ||||
| Natural transmitters. | Lice. | Lice Ticks (Argas persiscus). (Sergent.) |
Lice. (?) Bed bug (Acanthia lectularia). |
Ticks (Ornithodoros moubata). | Lice (?) Ticks (Ornithodoros talaje) (?). |
Lice (?)Bug (Cimex rotundatus). | |
| Serum reactions | ? | Immune serum possibly without effect on S. recurrentis (obermeieri). |
Immune serum without any effect on S. novyi or duttoni. |
Immune serum without any effect on S. novyi or recurrentis (obermeieri). |
Immune serum without any effect on S. recurrentis (obermeieri), duttoni, or carteri. |
Immune serum without any effect on S. novyi. |
For a summary of the symptoms evoked by the various strains of relapsing-fever spirochæte, see the Table on p. 242.
Mortality.— The death-rate is usually below 6 per cent. In the feeble and old, death may take place at the height of the first paroxysm.
Diagnosis.— This disease is readily confounded with malaria, enteric, typhus, and influenza. The detection of the spirochætes with the microscope, or by animal injection, is the most reliable method of diagnosis. At an early stage the relapsing character of the clinical phenomena, not having declared itself, is not available as an aid to diagnosis, but at a later period the history of a fever which had relapsed about fourteen days from the commencement of the disease should be regarded as highly suggestive of relapsing fever.
Morbid anatomy.— The spleen is usually large and soft. Liver, kidneys, and heart show cloudy swelling. The skin in fatal cases is usually jaundiced, and there may be submucous petechue. The bonemarrow is hyperæmic. There is generally a marked polymorphonuclear leucocytosis.
Treatment.— Ehrlich's discovery of the value of salvarsan in the treatment of syphilis naturally suggested that this drug would prove of use in the other spirochæte-caused diseases— yaws and relapsing fever. Fortunately the surmise has proved to be well founded. Intravenous injection of from 3 to 6 gr. of salvarsan and similar arsenicals in relapsing fever, after a short aggravation of symptoms is promptly followed by disappearance of the spirochætes from the blood and, in the vast majority of cases, recovery. Should relapse occur— a rare event— a second injection may be given.
Atoxyl, so potent against trypanosomiasis, is useless in relapsing fever.
Methods of administering salvarsan.— Salvarsan (dioxy- diamido-arseno-benzol, " 606 ") is sold as a yellow powder hermetically sealed in glass phials. It may be given intravenously, intramuscularly, subcutaneously, or by the mouth in alkaline solution.
Of these, the intravenous and intramuscular methods are the ones to be recommended; the subcutaneous, and occasionally the intramuscular, injections are apt to be followed by such extensive sloughing as to require surgical interference.
The intramuscular injection a suspension of the drug in oil—is generally made into the buttocks: the dose is 7-8 gr. (0.4-0.5 grm.) in the male; 4½ gr. (0.3 grm.) in the female, and ½ gr. (0.03-0.04 grm.) for each year of age in children is taken as the standard.
For intravenous injection the glass phial containing 9 gr. (0.6 grm.) is taken, the contents carefully added to 50 c.c. physiological saline solution (made with freshly distilled water), and dissolved thoroughly by adding 18-23 drops of 15-per-cent. soda till a precipitate forms which redissolves on addition of more soda. The solution should be made up to 300 c.c. In a man the whole amount may be injected; in a woman, 200 c.c. or less.
The vein should be exposed and the needle, attached to a funnel and a glass- jointed rubber tubing, inserted. Care should be taken that the funnel and tubing are filled with saline beforehand and all air excluded, the flow being controlled by a clip or a stopcock. A special apparatus has been devised and placed on the market by Martindale.
It is advisable to run into the vein 100-200 c.c. of normal saline first, and then to add the salvarsan solution warmed to the temperature of the body.
Neo-salvarsan is an oxidized product of salvarsan, possessing the advantage of being less toxic and more soluble; consequently it may be given in larger doses, 15 gr. being tolerated by an adult man. It is, therefore, preferable to the older product. It is easily soluble in normal saline, forming a neutral solution.
According to Levaditi the most favourable time for the administration of salvarsan is during the "precritical " period of the spirochætal infection, when it causes a precocious crisis, thus enabling the organism to combat the infection by the usual processes—spirochæticidal bodies and phagocytosis.
Serum-therapy.— Novy and Knapp have proved that active immunity follows recovery from spirochæte infection, and that this immunity can be increased to a remarkable degree by successive injections of spirochæte-infected blood. They have further shown that passive immunity can be imparted by the injection of recovered or of hyperimmunized blood, and that both active and passive immunity persist for months. Preventive inoculations have been successfully practised in rats, mice, and monkeys. Infected animals can be promptly cured by the injection of hyperimmunized serum, and relapses can be prevented by the same means. Although Todd has not been so successful in similar experiments, it seems probable that we have in these observations a basis for the prevention and cure of relapsing fever in man.
Prevention.— The fact that the spirochæte is conveyed to man by bug, or louse, or tick bite indicates that personal and domestic cleanliness and the avoidance of people and places infested with such vermin must form the basis of successful prophylaxis. Especially to be avoided in Africa are the resting-places of caravans and travellers, and the huts of natives. The mosquito net, a bed well off the ground, and a night-light are indispensable in that country, where the nocturnal habits of Ornithodoros moubata render the hours of sleep especially dangerous.
TICKS
Recent developments in human and veterinary pathology have shown that ticks play an important part in the transmission of disease. They are widely distributed, almost every animal either having species special to itself or being liable to attack by species of a wider zoological range. They belong to the order of the Acarina, of which they are by far the largest forms. They are always visible to the naked eye, and the females are almost invariably larger than the males. In some species the ovigerous females, when gorged with blood, may reach a length of nearly half an inch. As a rule they are temporary parasites, but some live in a quasi-permanent manner on the body of their host; and occasionally a few, as the sheep tick, Ixodes reduvius (Plate VI., 2), may even burrow beneath the skin. They differ from insects in possessing four pairs of legs, and in having the three regions of the body— head, thorax, and abdomen— fused into one unarticulated mass. This latter feature also distinguishes them from the spiders, in which the abdomen is clearly distinct from the cephalothorax.
After impregnation the female tick attaches herself to her host. Becoming enormously distended with its blood, she drops off and secretes herself in some convenient hiding-place where she deposits her eggs, which are small, yellowish, roelike grains, amounting in some cases to thousands. Oviposition begins from two to ten days after the host has been quitted, and goes on for several days. In due course (two or three weeks under favourable conditions) the eggs are hatched. The larvæ look like minute moving grains of sand. They are characterized by having only three pairs of legs, no stigmata, and no sexual orifice. A suitable opportunity presenting, the larva attaches itself to its vertebrate host. After a period of growth it goes through a first moult (ecdysis), and emerges from its larval skin as a nympha, provided with eight legs instead of six, and with a pair of large stigmata placed, one cm. each side of the body, behind the fourth pair of legs. After a second period of growth and a second moult it becomes sexually mature. In some species, as in the case of Margaropus bovis, the metamorphosis from larva to nymph, and from nymph to imago, takes place upon the same host, the parasite remaining attached during the process. In other species, as in the case of Hœmaphysails leachi, the tick, before each moult, drops off as soon as it ceases feeding, and in consequence has to find a host three times during its life instead of once. Having reached maturity, the sexes unite. After fertilization the male dies, but the female proceeds to engorge herself with blood for the development of her ova.
On account of the difficulty of finding an appropriate host, ticks at all stages are endowed with a phenomenal capacity for fasting. Megnin found Argas persicus alive after a fast of four years' duration.
Ticks are referable to two families, the Ixodidœ and Argasidœ, differing both in structure and in life habits. Their characteristics and generic classification are indicated sufficiently for practical purposes in the synoptical Table on p. 248.
The species which are of particular interest to the human pathologist are Ornithodoros moubata, O. savignyi, Argas persicus, and Dermatocentor venustus— the first two being the transmitters of tbe spirochæte of African relapsing fever; the third, of the spirochæte of the miana disease (Balfour). It is quite likely that other species will in the future ba found to be concerned in the transmission of disease germs to man. Important animal diseases due to Spirochœtœ and Babesiœ are also known to have tick transmitters. Spirochœtœ gallinarum of fowls in Brazil is transmitted by Argas miniatus. Babesia bigemina (bovis) is conveyed in various countries by different species of Margaropns, such as M. annulatus (Plate VI., 1), M. australis, M. decoloratus; Theileria parva by Rhipicephalus appendiculatus and R. simus; Babesia ovis by R. bursa; Nuttallia equi by R.evertsi, and Babesia canis by Hœmaphysalis leachi and Dermacentor reticulatus.
Ornithodoros moubata (Murray) (O. savignyivar. cœca, Neumann) is extensively distributed throughout tropical Africa (Plate VI., 3). Its body is rotund and is oval in outline. Its colour, when alive, is greenish brown. The integument is hard, leathery, covered with close-set shining granules or tubercles, and marked both above and below with
symmetrically arranged grooves. The females may attain about 8 mm, in length by 6 to 7 mm. in breadth, and moult 
Ticks (females).
1. Margaropus (Boophilus) annulatus (partially distended); 2, Ixodes reduvius (partially distended); 3, Ornithodoros moubata; 4. Argas persicus.
Plate VI.
In habit Ornithodoros moubata resembles the common bed-bug. It lives in the huts of the natives, hiding during the day in cracks in the walls and floors, or in the thatched roofs, and moving about actively during the night in search of nourishment. It attacks both man and beast. It feeds slowly, and would be unable to get much blood from any but a sleeping person. Dutton and Todd observed that a big female might remain, firmly fixed, feeding on a monkey for two or three hours before it finally dropped off, distended to the size of a cherry. O. moubata deposits its eggs in batches of fifty, seventy, or a hundred. Dissection has shown that only a few eggs mature at a time. The fertility of the female is favoured by liberal feeding. The females lay batches of eggs after each feed, but do not continue to moult. The eggs hatch in about twenty days. In the case of this tick, Dutton and Todd have observed that the larval stage is practically omitted. About seven days after oviposition the hexapod larva can be seen to be forming within the translucent egg-shell. About the thirteenth day the egg-shell splits, and about the same time the larval skin splits also, and the eight-legged nymph throws off simultaneously both the egg-shell and its larval skin. There are several nymphal stages; the exact number has not been clearly ascertained. The largest nymphs may equal adults in size, and show a punctiform mark where the sexual orifice is situated in the adult.
An interesting feature, and one perhaps having a bearing on the etiology of tick-transmitted diseases, pointing as it does to a channel by which the egg.s may receive a germ ingested by the parent, concerns certain cells in the stomach wall. The tick, while feeding, from time to time expels per an uni a whitish material. This excretion is derived partly from the Malpighian tubes, and partly from the cells alluded to. In the stomach wall, nourished by the imbibed blood, these cells elongate towards the cavity of the ventricle; the other end, smaller and becoming clavate, splits and emits the elaborated nutriment into the general body cavity, where it mixes with the blood of the tick. The cell then, becoming globular, drops into the lumen of the stomach, constituting part of the white excretion expelled per anum. One can readily understand how, by the former route, a parasite could reach the tissues of the tick, including the ovaries. Balfour has infected chickens with S. gallinarum by feeding them on eggs of infected Argas miniatus (persicus).
O. moubata is especially common along the routes of travel. The rest-houses are always the most infested. The ticks are frequently carried long distances in mats or bedding, or in porters' loads which have been piled for safety in the rest-huts at night.
The natives of some places, and also the Boers, protect
| Rostrum terminal. Dorsal shield present. Sexual dimorphism marked |
Family Ixodidæ | Anal groove surrounding anus in front. | Prostriata Ixodinæ | Inornate, without eyes and without festoons. Spiracles round or oval. Palps of variable form. Tarsi without spurs. Sexual dimorphism pronounced. In the ♂ the venter is covered by non-salient plates; one pregenital, one median, one anal, two adanal, and two epimeral plates. Parasitic on Ungulata, carnivora, rodents, marsupials (kangaroo), bats, and birds. | 1. Genus Ixodes. | ||||
| Anal groove containing anus behind. | Metastriata | (a) Brevirostrata. Rostrum short. Inornate, without eyes but with festoons. Usually with short conical palps, whose second articles project laterally. Small size and slightly chitinized. Sexual dimorphism slight. The ♂ shows no ventral plates or shields. |
2. Genus Hæmaphysalis. | ||||||
| Usually ornate, with eyes and festoons. Short, broad, or moderate palps, and basis capituli rectangular dorsally. Spiracles sub-oval or comma-shaped. | 3. Genus Dermacentor. | ||||||||
| Inornate, with eyes and festoons. Short palps, with basis capituli hexagonal dorsally with prominent lateral angles. The ♂ resembles Rhipicephalus dorsally, Dermacentor ventrally. Spiracles sub-triangular or comma-shaped. | 4. Genus Rhipicentor. | ||||||||
| Usually inornate, with eyes and festoons. Short palps, and basis capituli usually hexagonal dorsally. The ♂ possesses a pair of adanal shields and usually a pair of accessory adanal shields. Spiracles bluntly or elongate comma-shaped. | 5. Genus. Rhipicephalus. | ||||||||
| Inornate, with eyes, but indistinct festoons. Short palps, and capitulum intermediate between that of Rhipicephalus and Boophilus. Highly chitinized. The ♀ with very small scutum. The ♂ with a median plate prolonged into two spines projecting beyond and to either side of the anus. Anal groove obsolete. Spiracles rounded or short, oval in both sexes. | 6. Genus Margaropua. | ||||||||
| Inornate, with eyes, but indistinct festoons. Very short compressed palps ridged dorsally and laterally. Basis capituli hexagonal dorsally. Slightly chitinized. Unfed adults of small size. The ♀ with small scutum. The ♂ with adanal and accessory adanal shields. Spiracles rounded or oval in both sexes. No anal groove. | 7. Genus Boophilus. | ||||||||
| (b) Longirostrata. Rostrum long. Ornamentation absent or present, at times confined to the legs; with eyes, with or without festoons. Long palps. Basis capituli subtriangular dorsally. The ♀ approaching Amblyomma. The ♂ with a pair of adanal shields, and with or without accessory adanal shields, and two posterior abdominal protrusions capped by chitinized points. Spiracles comma-shaped. |
8. Genus Hyalomma. | ||||||||
| Generally ornate, with eyes and with festoons. Long palps, of which the second article is especially long. Basis capituli of variable form. The ♂ without adanal shields, but small ventral plaques are occasionally present close to the festoons. Spiracles subtriangular or comma shaped. Sub-genus Aponomma. Devoid of eyes, or in which the eyes are poorly developed. Body frequently very broad. Occur almost exclusively on reptilia. |
9. Genus Amblyomma. | ||||||||
| Rostrum concealed by overlapping cephalothorax. Dorsal shield absent. Sexual dimorphism slight. |
Family Argasidæ | Body usually flat with thin edges. Ventral grooves absent or very shallow. Eyes absent. | Genus Argas. | ||||||
| Body with thick edges. Ventral grooves present. Eyes sometimes present. | Genus Ornithodoros. | ||||||||
In certain parts of Africa the distribution of O. moubata is overlapped by that of a closely allied species, O. savignyi, which is more diurnal in its habits and seems to have a predilection for market-places, cattle-stands, etc. O. savignyi differs from O. moubata in being provided with eyes, in having larger processes on the legs, and a more minutely pitted dorsal surface. O. savignyi has been recorded from Egypt, Nubia, Abyssinia, Somaliland, British East Africa, etc., as well as from southern Asia. It also may be concerned in the transmission of African relapsing fever or other disease. Its bite is dreaded by the natives.
Argas persicus (Fischer), A. miniatus (Koch) (Plate VI., 4), has a flat, thin, oval body of a yellowish, greenish, or reddish colour, spotted on the back with a great many white granulations; the legs are pale yellow. Its distribution is cosmopolitan; it is found more commonly in the north and east of Persia, also in Syria, Turkestan, Russia, China, Algeria, and Cape Colony, in North and South America and the West Indies, West Australia, and Queensland. It attacks both poultry and human beings. Its habits are similar to those of Ornithodoros moubata; it infests old houses, living in the cracks of walls and floors. Kotzebue says that in Persia it may so infest villages as to drive out the inhabitants.
- ↑ * Journal of Infectious Diseases, 1906.
- ↑ * Arch, fur Protistenkunde, 1912.
- ↑ * Recently doubt has been cast on the validity of Leishman's and Balfour's work on this subject by Marchoux and Couvy, who conclude that the granules in the tick bear no relation to the spirochætes.
- ↑ * In the act of feeding, the tick occasionally voids excrement and exudes a few drops of a fluid secreted by the coxal glands situated in the first intercoxal space. The coxal fluid dilutes the fæces, thereby facilitating access to the wound inflicted by the bite of the tick or by scratching.