Tropical Diseases/Chapter 40

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Tropical Diseases
by Patrick Manson
Chapter 40 : Parasites of the Circulatory and Lymphatic Systems
3235441Tropical DiseasesChapter 40 : Parasites of the Circulatory and Lymphatic SystemsPatrick Manson

Section V. ANIMAL PARASITES AND ASSOCIATED DISEASES

CHAPTER XL

I. PARASITES OF THE CIRCULATORY AND LYMPHATIC SYSTEMS

FILARIASIS

History.— Our knowledge of this subject dates from the discovery by Demarquay, in 1863, of a larval nematode— microfilaria bancrofti (Plate X.) —in the milky fluid from a case of chylous dropsy of the tunica vaginalis. Later, in 1866, Wiicherer found the same organism in the urine of a number of cases of chyluria. In 1870 Lewis made a similar observation in India, and in 1872 discovered that the blood of man was the normal habitat of this larval parasite, which he named, accordingly, Filaria sanguinis hominis. Four years later Bancroft, in Brisbane (Queensland), discovered the adult form, and Cobbold named it Filaria bancrofti. Since that time the subject has rapidly expanded, and its great practical importance in tropical pathology is now recognized.

Nomenclature of the parasites.— I have pointed out that Lewis's microfilaria*[1] is not the only blood-worm in man, and that the human circulation is the habitat of the larvae of no fewer than five, possibly of six or even more, distinct species of filariæ. In consequence of this discovery, it was deemed advisable to modify the original name of Lewis's filaria. This I proposed to call Filaria nocturna; but as, in accordance with the rules of zoological nomenclature, precedence must be given to the name previously suggested by Cobbold for the adult form, I propose to call the larval form microfilaria bancrofti (Fig. 96, a). The other filariæ of the blood I named F. diurna

Fig. 96.—(a) Microfilaria bancrofti, x 300; (b) microfilaria loa, Africa, x 300; (c) microfilaria demarquaii, St. Vincent, x 300; (d) microfllaria ozzardi and microfilaria perstans, British Guiana, x 300; (e) microfilaria perstans, Africa, x 300

(mf. loa), Fig. 96, b; F. demarquaii (mf. demarquaii), Fig. 96, c; F. ozzardi, (mf. ozzardi), Fig. 96, d (a doubtful species); F. perstans (mf. perstans), Fig. 96, e; and F. magalhãesi, after its describer. (Plate X.)

Their pathological importance.—Only one of these parasites, so far as we know at present, appears to

Microfilariæ of the blood.
1. Mf. bancrofti; 2. mf. perstans; 3. mf. loa; 4. mf. demarquaii.

Plate X.

have important pathological bearings— Filaria bancrofti, which, in its adult stage, inhabits the lymphatics of man. As regards the others, with the exception of F. loa, we have no knowledge of any serious pathological significance they may possess. There can be

no question of the importance in tropical pathology of F. bancrofti; there is abundant reason to believe that it is the cause of endemic chyluria, of various forms of lymphatic varix, and of other obscure tropical diseases, including, probably, elephantiasis.

FILARIA BANCROFTI (Cobbold, 1877).

Synonyms.Filaria sanguinis hominis; F. nocturna; F. wuchereri.

Geographical distribution and prevalence.— The geographical distribution of Filaria bancrofti is very extensive. It has been found as an indigenous parasite in almost every country throughout the tropical and sub-tropical world, as far north as Spain in Europe and Charleston in the United States of America, and as far south as Brisbane in Australia. In many places— South China, for example— quite 10 per cent., and in other places half of the population harbour it. I have ascertained that it is probable that one-third of the inhabitants of at least one district in India— Cochin— carry blood filarise. I also find that in some of the South Sea Islands— Samoa, for example fully one-half of the people are affected in this way. Thorpe has shown that in the Friendly Islands 32 per cent, of the people harbour this filaria. We have similar testimony as to the great frequency of the parasite in Madras from Maitland and others, in Demerara from Daniels, in several of the West India Islands from Low, in West Africa from Annett, Button, and Prout. Doubtless, if diligently and systematically sought for, it could be found in most tropical countries.

Demonstration of blood microfilariæ.— Whoever would investigate the subject of filariasis will find that, in order practically to comprehend the subject and to provide himself with abundant material for observation, it is advisable to make systematic examination of the blood of the inhabitants of some district in which filariasis is endemic. If this be done, the observer is sure to come across, sooner or later, cases in which microfilaria bancrofti abounds, and also of the diseases to which it gives rise.

Technique.—I recommend the following procedure as likely to supply the investigator not only with material, but also with much useful information. Let him visit, late in the evening, some hospital, or prison, or other establishment where he can have an opportunity of examining the inmates, and let him procure slides of the blood of, say, 100 individuals. The slides are conveniently prepared by pricking the finger of each person in turn, and transferring large drops of the blood so obtained to ordinary microscope slips by simply dabbing the centre of the slip on the blood. The blood is then spread out with a needle so as to cover in a moderately thin film about a square inch of one surface of each slip. Each slip, so soon as the blood is spread, should be laid on its uncharged surface on a smooth, level surface until dry; it is then labelled and put aside. One preparation of this description may be made from each person, who should be selected simply as a representative of the general population, and therefore irrespectively of his being physically sound, or of his being the subject of any particular type of disease.

The slides may be examined in various ways, either at once or, if more convenient, weeks or months afterwards; if kept dry and away from cockroaches, ants, etc., they do not spoil. A convenient plan is to dip the slides, without previous fixing, in a weak solution of fuchsin—about three or four drops or more of the saturated alcoholic solution to the ounce of water. They are left in the stain for about an hour, and then examined wet and without cover-glass. If the slides are old, they may stain too deeply; in this case they may be partially decolorized in weak acetic acid—two or three drops to the ounce of water—and afterwards washed. Recent slides, if placed in water for a few minutes until the hæmoglobin is discharged, show the microfilariæ very well; it is advisable, however, for the novice at this sort of work to use, in the first instance, the fuchsin method described above.

Another plan is to fix the blood-film with alcohol, and then to stain by running on a few drops of saturated watery solution of methylene blue, washing off the superfluous stain after half a minute, and, if necessary, decolorizing with weak acetic acid and washing; the wet slide is then examined with the microscope. Or, without previous fixing with alcohol, the slide, after it has dried, may be dipped for a few seconds in distilled water so as to wash out the hæmoglobin, dried, and then, with or without fixing, stained with methylene blue, logwood, or other suitable stain.

An inch or half-inch objective and a mechanical stage with a parallel movement will enable the investigator to pass rapidly in review the whole of the blood on the slide. In unfixed slides, if microfilariæ are present, they will be detected readily; the hæmoglobin of the blood corpuscles being dissolved out by the watery stain, the nuclei of the white blood-corpuscles and any microfilariæ that may be present are the only coloured objects visible on the slide, and therefore at once catch the eye.

In any district in which the filaria is moderately common, out of 100 slides prepared in this way from as many individuals, probably eight or ten will be found to contain the parasite. When microfilariæ have been detected, the persons from whom the parasite-bearing slides came may be used afterwards as a source of supply for further examinations and study.

Demonstration of living microfilariæ.—When it is desired to study the living microfilaria, all that is necessary is to make three or four ordinary wet preparations of the blood of a filaria-infected person—making them during the evening or night, and ringing the cover-glasses with vaseline so as to prevent the slides from becoming dry. In such preparations, if kept cool, the microfilariæ remain alive for a week, or even longer, and can readily be detected by their movements, an inch or half-inch objective being used in the first instance as a searcher.

Permanent preparations.—Permanent preparations may be made by fixing very thin films of blood with alcohol or heat, staining with methylene blue, eosin, etc., and mounting in xylol balsam. It is generally advisable before fixing to wash out the hæmoglobin with water or very weak acetic acid. Logwood is perhaps the best stain; it brings out the sheath very distinctly, and picks out the nuclei. Double staining with eosin and logwood shows very well the structure of the musculo-cutaneous layer of the worm, in addition to other anatomical details.

Description of larval form.—Examined in fresh blood, microfilaria bancrofti (Fig. 97) is seen to be a minute, transparent, colourless, snake-like organism, which, without materially changing its position on the slide, wriggles about in a state of great activity, constantly agitating and displacing the corpuscles in its neighbourhood. At first the movements are so active that the anatomical features of the microfilaria cannot be made out. In the course of a few hours the movement slows down, and then one can see that the little worm is shaped like a snake or an eel; that is to say, that it is a long, slender, cylindrical organism, having one extremity abruptly rounded off, and the other for about one-fifth of the entire length gradually tapered to a fine point. On measurement, it is found to be a little over or under 0·3 mm. in length by 0·008-0·011 mm. in diameter—about the diameter of a red blood-corpuscle.

When examined with a low power, it appears to be structureless; with a high power a certain amount of structure can, on close scrutiny, be made out. In the first place, it can be seen that the entire animal is enclosed in an exceedingly delicate, limp, structureless sack, in which it moves backwards and forwards (Fig. 97, a). This sack, or "sheath," as it is generally called, although closely applied to the body, is considerably longer than the worm it encloses; so that that part of the sack


Fig. 97.—Anatomy of mf. bancrofti.
a a, Sheath; b, central viscus; c, v spot; d, tail spot.

which for the time being is not occupied is collapsed and trails after the head, or tail, or both, as the case may be. It can be seen also that, about the posterior part of the middle third of the parasite, there is what appears to be an irregular aggregation of granular material which, by suitable staining, can be shown to be a viscus of some sort (Fig. 97, b) . This organ

Distinguishing features between mf. bancrofti and mf. loa, in stained specimens.
Attitudes (1) of mf. bancrofti. (2) of mf. loa; heads (3) of mf. bancrofti, (4) of mf. loa; tails (5) of mf. bancrofti, (6) of mf. loa.
Plate XI.

runs for some distance along the axis of the worm. Further, if a high power be used, a closely set, very delicate transverse striation can be detected in the musculo-cutaneous layer throughout the entire length of the animal. Besides this, if carefully looked for at a point about one-fifth of the entire length of the organism backwards from the head end, a shining, triangular V-shaped patch (Fig. 97, c) is always visible. What may be this V spot is brought out by very light staining with dilute logwood. The dye brings out yet another spot (Fig. 97, d), similar to the preceding, though very much smaller; this second spot is situated a short distance from the end of the tail. The former I have designated the "V spot," the latter the "tail spot." These spots are probably connected with development, the V spot being the rudiment of the future water-vascular system, the tail spot that of the anus or cloaca and posterior part of the alimentary canal. The spots (Fig. 97, c, d) are not stained by strong logwood or by the aniline dyes. Staining with logwood also shows that the body of the little animal is principally composed of a column of closely packed, exceedingly minute cells enclosed in a transversely striated musculo-cutaneous cylinder (Fig. 97); at all events, many nuclei are thereby rendered visible. Low has pointed out to me that the break seen in all stained specimens in the central column of nuclei occurs at a point slightly anterior to the V spot. This break can only be recognized in stained preparations.

Rodenwaldt and Fülleborn, by careful study of specially stained specimens, have further elucidated the histology of the microfilaria, which is fully illustrated in Figs. 98 and 128 borrowed from Fülleborn, special attention being directed to the excretory and genital cells and substances in the rudimentary intestinal canal.[2] (See also Plate XI.)

When the movements of the living microfilariæ have almost ceased, by careful focusing it can be seen that the head end is constantly being covered and uncovered by a six-lipped—or hooked—and very delicate prepuce; and, moreover, one can sometimes see a short fang of extreme tenuity, based apparently on a highly retractile granule, suddenly shot out from the uncovered extreme cephalic end, and as suddenly retracted (Fig. 99 a, c, d).

Filarial periodicity.—A singular feature in the life of the microfilaria is what is known as "filarial periodicity."

If under normal conditions of health and habit the blood be examined during the day, the parasite is rarely seen, or, if it be seen, only one or two specimens at most are encountered in a slide. It will be found, however, that as evening approaches, commencing about five or six o'clock, the microfilariæ begin to enter the peripheral circulation in gradually increasing numbers. The swarm goes on increasing until about midnight, at which time it is no unusual thing to find

Fig. 98.—Minute anatomy of a microfilaria, and differential points of structure between mf. loa and mf. bancrofti. (After Fulleborn.)

N., Nerve ring (ant. break in cell column); A., ant. v-spot (exc. pore); Ex.C., excretory cell; C.G., granular mass (or Innenkörper); G. 1-4, "genital cells"; P., posterior or tail spot; M., granules in mouth cavity, T., granules in tail; Sh., sheath.

as many as three hundred, or even six hundred, in every drop of blood; so that, assuming that the parasites are evenly distributed throughout the circulation, it may be inferred that as many as forty or fifty millions are simultaneously circulating in the blood-vessels. After midnight the numbers begin gradually to decrease; by eight or nine o'clock in the morning the microfilariæ have disappeared from the peripheral blood for the day. This nocturnal periodicity is, under normal conditions, maintained with the utmost regularity for years. Should, however, as Mackenzie has shown, a filarial subject be made to sleep during the day and remain awake at night, the periodicity is reversed; that is to say, the parasites come into the blood during the day and disappear from it during the night. It cannot be the sleeping state, as some have conjectured, that brings about this periodicity; for the ingress of the microfilariæ into the peripheral blood commences three or four hours before the usual time for sleep, and the egress several hours before sleep is concluded, and this egress is not

Fig. 99.—Structure of head end of mf. perstans (a, b), and of mf. bancrofti (c, d).

complete until several hours after the usual time of waking. This night swarming of the larvæ of F. bancrofti in the peripheral circulation seems to be an adaptation correlated to the life-habits of its liberating agent, the mosquito, Culex fatigans, its usual intermediary host.

Some years ago I had an opportunity of ascertaining that during their diurnal temporary absence from the peripheral circulation the microfilariæ retire principally to the larger arteries and to the lungs, where, during the day, they may be found in enormous numbers.

The patient on whom this observation was made was the subject of lymph scrotum and varicose groin glands. His blood contained large numbers of embryo filariæ which exhibited the anatomical features and periodicity characteristic of microfilaria bancrofti. One morning he committed suicide by swallowing a large quantity of dilute hydrocyanic acid. Death was almost instantaneous. At the post-mortem examination, made six hours later, a huge lymphatic varix was found occupying the pelvis and back part of the abdominal cavity. In the dilated lymphatic vessels many adult filariæ—F. bancrofti—were found. The distribution of the microfilariæ was studied by counting them in drops of blood expressed from the various organs, and also in sections. The result is summarized in the following tables:—

ENUMERATION OF MICROFILARIÆ IN A DROP OF BLOOD
EXPRESSED FROM THE FOLLOWING ORGANS

Organ No. of
slides
Aggregate No.
of microfilariæ
Average per
slide
Liver  3    2     2/3
Spleen  3    3   1
Brachial venæ comites  4   111  28
Bone marrow  1    0   0
Muscle of heart  3  365 122
Carotid artery  1  612 612
Lung 10 6,751 675


ENUMERATION OF MICROFILARIÆ IN SECTIONS OF THE
FOLLOWING ORGANS

Organ No. of
sections
Aggregate No.
of microfilariæ
Average per
section
Liver 10   3  0·3
Spleen  4   0  0·0
Kidney  8  13  1·6
Brain  4   4  1·0
Muscle (voluntary)  3   2   0·33
Heart muscle  4  68 17·0
Lung  6 301  50·16
Lobe of ear  4   1   0·25
Scrotum  4   0  0·0

In the lung sections (Fig. 100) the microfilariæ lay outstretched or variously coiled in the vessels, large and small. In the heart-muscle they lay along the capillaries between the fibres; in the kidneys they seemed specially to affect the Malpighian tufts; a very few were found in the capillaries of the brain; vast numbers were found in smears from the inner surface of the carotid arteries. The preparations afforded no explanation as to how the microfilariæ contrive to maintain their position in the blood current, or as to the forces determining their peculiar distribution. Their absence from the liver and spleen is a remarkable fact.

Since this was written they have been found in the spleen tissue by other observers. The capillaries of the lung appear to be the favourite habitat of microfilariæ. Microfilaria immitis, mf. perstans, and the non-periodic Fijian microfilariæ have been found in greatest abundance in this situation.

Non-periodic microfilaria bancrofti.—Until recently it was believed that, in natural conditions of health and habit on the part of the human

Fig. 100.—Section of lung showing microfilariæ in the blood-vessels.
(From a microphotograph by Mr. Spitta.)

host, nocturnal periodicity was uniformly observed by the microfilaria of Filaria bancrofti at all times and in any country. Many years ago Thorpe remarked that in Tonga and Fiji the filaria could be found often in great abundance in the blood during the daytime; and in 1906 Ashburn and Craig found a microfilaria in the Philippines which showed no periodicity, and which these authors, relying on this feature, considered a distinct species and named F. philippinensis. Wilson, in 1909, after a systematic study of the point in a considerable number of cases in Fiji, also considered that the local filaria was non-periodic— an observation amply confirmed by Bahr in 1910. Similarly, Fülleborn found that the micronfilaria of Samoa showed no periodicity. Strange to say, the filaria of neighbouring islands in the Pacific— namely, the Solomons, New Guinea, and the Bismarck Archipelago— are strictly periodic in their blood appearances.

Bahr has shown that the filaria of Indian immigrants who had acquired their filarial infections in India retain their periodic habits during at least three years of residence in Fiji, and that if an Indian or a Solomon Islander acquires the infection in Fiji the microfilarise are non-periodic in habit. Connal and Thiroux, in a proportion of instances of filarial infection in West Africa, have found the microfilarise to be non-periodic,*[3] whilst in other instances they exhibit the nocturnal habit just as those of India, China, and America are known to do.

As an explanation of this striking anomaly it has been suggested that the non-periodic microfilaria is the progeny of a parent worm specifically distinct from F. bancrofti; but Leiper has failed to find any difference between the Fijian mature worm and the F. bancrofti of India, China, and South America; and Fülleborn and Bahr, after minute study and comparison of the histology of the microfilariæ from those countries, find that they are identical in every respect. It may be, as Bahr suggests, that the non-periodic habit of the Pacific microfilaria is a partial adaptation to the day habit of its usual intermediary in Fiji Stegomyia pseudoscutellaris. (Plate XII.)

The subject of filarial periodicity, especially as regards the blood worms of the Pacific islands and West Africa, requires further study.

The mosquito the intermediary host of Filaria bancrofti.— Should the" females of certain

Stegomyia pseudoscutellaris, ♀.
Plate XII.

species of mosquito[4] which have fed on the blood of a filaria-infested individual be examined immediately after feeding, the blood contained in the stomach of the insects will be found to harbour large numbers of living microfilariæ. If one of these mosquitoes be examined three or four hours after it has similarly fed, it will be found that the blood corpuscles have in great measure parted with their hæmoglobin, and
Fig. 101.—Filarial ecdysis.
that the blood plasma in consequence of this and of dehydration has become thickened, although not coagulated. If attention be directed to the microfilariæ in the thickened blood, it will be seen that many of them are actively engaged in endeavouring to escape from their sheaths. The diffused hæmoglobin has so thickened the blood plasma that it has become viscid, and holds, as it were, the sheath. This change in the viscosity of the blood seems to prompt the microfilariæ to endeavour to escape from their sheaths. They become restless, as if excited. Alternately retiring towards the tail end and then rushing forward to the head end of the sheath, the imprisoned parasite butts violently against the latter in frantic efforts to escape. After a time, the majority succeed in effecting a breach and in wriggling themselves free from the sheaths which had hitherto enclosed them (Fig. 101).[5] The microfilaria now swims free in the blood, the character of its movements once more undergoing a remarkable change. Hitherto, though active enough in wriggling about, the parasite did not materially change its position on the slide; but
Fig. 102.—Section of thoracic muscles of mosquito, showing microfilariæ between the fibres: first day after the insect has fed on a filariated patient. (From a microphotograph by Mr. Spitta.)

now, having become free, it moves about from place to place—locomotes, in fact. If we dissect a mosquito at a somewhat later period after feeding, it will be found that the stomach of the insect, though still full of blood, contains very few microfilariæ, although their empty sheaths can be seen in abundance. If, however, we break up with needles the thorax of the insect and tease out in normal salt solution the muscular tissue, we shall find that the microfilariæ, after discarding their sheaths, have

Fig. 103.—Section of thoracic muscles of mosquito seven days after it had fed on a filariated patient. (From a microphotograph by Mr. Spitta.)

quitted the stomach and entered the thoracic muscles of the insect, among the fibres of which they are now moving languidly. (Figs. 102-8.) By a course of serial dissections of filariated mosquitoes we can ascertain that in the thorax of the insect the parasite enters on a metamorphosis which takes from twelve to twenty days (longer or shorter, according to atmospheric temperature) to complete—a metamorphosis eventuating in the formation of a mouth, of an alimentary canal, and of a peculiar trilobed caudal end, as well as in a relatively enormous increase in the size (to 1/16 in.) and activity of the young parasite. The filariæ now quit the thorax.

A few find their way to the abdomen, where, in properly prepared sections, they may occasionally be seen in the tissues around the stomach, and even among the eggs at the posterior part of the abdomen. The vast majority pass forwards by the prothorax and neck, and, entering the head, coil themselves up

Fig. 104.—Section of thoracic muscles of mosquito about twelve days after it had fed on a filariated patient. (From a microphotograph by Mr. Spitta.)

close to the base of the proboscis and beneath the pharynx and under-surface of the cephalic ganglia. Low, in sections prepared at the London School of Tropical Medicine from filariated mosquitoes sent to me by Bancroft of Australia, has shown that the filaria in its future progress finds its way into the proboscis; an observation which has been confirmed by James in India, Annett and Button in West Africa, Bahr in Fiji, and others elsewhere. As pointed out by Grassi, its exact position here is the interior of the labium (Fig. 107, a). Apparently the filariæ seek to emerge (for such must be their object in entering the proboscis) in pairs; at all events, in those sections which I have examined, two worms were in each instance found together, their heads abreast of each other and close to the termination of the labium in the labella. As many

Fig. 105.—Larval filariæ (Dirofilaria immitis) leaving proboscis of mosquito and burrowing through the skin. (Partly diagrammatic, after Fülleborn.)

as eight have been found packed together in this situation.

The parasites remain in this position awaiting an opportunity to enter a warm-blooded vertebrate host when the mosquito next feeds on such. This they appear to do by penetrating the thin membrane that unites the labella to the tip of the proboscis, and so passing on to the surface of the skin, which they penetrate in the neighbourhood of the puncture made by the mosquito[6] (Fülleborn, Dirofilaria immitis; Bahr, Filaria bancrofti) (Fig. 105); they do not enter through the mosquito-made wound, as formerly conjectured, but near it. Apparently the filariæ in some instances can discriminate between flesh and vegetable, for in mosquitoes fed on bananas the parasites

Fig. 106.—Section of mosquito about sixteen days after it had fed on a filariated patient. The filaria has escaped from the thoracic muscles. (From a microphotograph by Mr. Spitta.)

had not been deceived into passing into so inhospitable a medium: up to forty days after the insect was infected, and after many meals of banana, they could still be found coiled up in the head or stretched out in the labium. Probably heat and moisture play a part in this respect, as has been shown to be the case by Fülleborn.

Fig. 107.—F. bancrofti in head and proboscis of mosquito.

a, a, a, Filariæ; b, labium; c, labrum; d, base of hypopharynx; e, duct of veneno-salivary gland; f, f, cephalic ganglia; g, g, eye; h, œsophagus; i, pharyngeal muscle.

These observations prove that, like the malaria parasite, the filaria is introduced into its human

definitive host by mosquito bite. Whether it may obtain an entrance by any other channel or medium it would be hard to prove and rash to deny. That the young filariæ can live in water for a time (about seven hours) is certain; it is conceivable that some of them, such as those which at the completion of their stage of development in the mosquito find their way into the abdomen of the insect, may escape into water when the mosquito lays her eggs or dies.*[7]

Technique.— Mr. Max Colquhoun made for me beautiful sections illustrating the metamorphosis of the filaria in mosquito by the following technique. The insects, preserved in glycerin, were soaked in dilute acetic acid 5 per cent, for one day only; then in formalin 50 per cent., water 50 per cent.,for one day; next in absolute alcohol for one day; absolute alcohol and ether, equal parts, one day; finally, in celloidin for one day. They were then sectioned, placed in strong hæmatoxylin for two hours, decolorized in acid, hydrochloric 1 per cent, and alcohol, washed in water, passed through aniline oil, xylol, and mounted in xylol balsam. Paraflin sections are not a success.

In working with fresh mosquitoes, all that is necessary is to tease up the thorax of the insect with needles in normal salt solution, and, after removing the coarse fragments of the integuments of the mosquito, apply a cover-glass and place under an inch objective. The filariæ are readily detected. If the slide is dried, fixed, and stained with a watery solution of some aniline dye or with logwood, and mounted in xylol balsam, beautiful permanent preparations will be obtained. Once introduced into the human body, the filaria finds its way into the lymphatics. Arrived in one of these, it attains sexual maturity, fecundation is effected, and in due course new generations of larval filariæ are poured into the lymph. These, passing through the glands—if such should intervene—by way of the thoracic duct and left subclavian vein or by the lymphatics of the upper part of the body, finally appear in the circulation.

Such is the life-history of Filaria bancrofti; man is its definitive host, the mosquito its intermediary host. It is manifest that filarial periodicity is an

Fig. 108.—Stages of larval form of F. bancrofti, from the thoracic muscles of Culex fatigans. (After Looss.)

adaptation of the habits of the parasite to the nocturnal habits of the mosquito. It is also manifest that the purpose of the "sheath" with which it is provided while circulating in the human host is to muzzle the young filaria and prevent its breaking through the blood-vessels, and thereby missing its chance of gaining access to the mosquito. The cephalic armature is adapted for piercing the walls of the mosquito's stomach, and for enabling the parasite to travel through the tissues of the insect.

Anyone desirous of working out for himself the metamorphosis of the filaria in the mosquito can readily do so, even in the absence of a suitable human subject, by setting Anopheles mosquitoes to bite filariated dogs. In most tropical countries a large proportion of the dogs harbour Filaria (Dirofilaria) immitis, whose larvæ circulate in the blood and are taken up by mosquitoes in the same way as F. bancrofti. (Fig. 109.) Grassi and Noè (confirmed by Bancroft, Sambon, and Low) have shown that the embryo F. immitis passes through the earlier stages of its metamorphosis in the Malpighian tubes of

Fig. 109.—Section of Dirofilaria immitis in the vena cava of a dog, to show the structure of a filaria on transverse section. Embryos are seen amongst the surrounding blood-cells. (After Bahr.)

1, Cuticle; 2, muscle cells; 3, perivisceral cavity; 4, inter-uterine septum; 5, alimentary canal; 6, ova.

Anopheles, whence, on attaining a certain stage of development, it passes forwards to the head of the insect, where it behaves in much the same way as F. bancrofti.

Parental forms.—The parent filariæ have been found many times. They are long, hair-like, transparent nematodes, 3-4 in. in length (Fig. 110). The sexes live together, often inextricably coiled about each other. Sometimes they are enclosed, coiled up several in a bunch and tightly packed, in little cyst-like dilatations of the distal lymphatics (Maitland); sometimes they lie more loosely in lymphatic varices; sometimes they inhabit the larger lymphatic trunks between the glands, the glands themselves, and, probably not infrequently, the thoracic duct.

The female filaria is the larger, both as regards length and

Fig. 110.—F. bancrofti (natural size): a, male; b, female.

thickness. It measures 85-90 mm. in length by 0·24-0·28 mm. in breadth. The two uterine tubes, occupying the greater extent of her body, are filled with ova at various stages of development. In both sexes the oral end, armed with a double row (number uncertain) of exceedingly minute papillæ (Fig. 111, b), is slightly tapered, club-shaped and simple; the tail (Fig. 111, a, c) also is tapered to comparatively small dimensions, its tip being rounded off abruptly. The vagina opens

Fig. 111.—Parental forms of F. bancrofti (magnified).
(a, Tail of male; b, head and neck; c, tail of female.

on the ventral surface about 1·2-1·3 mm. from the anterior extremity; the anus just in advance of the tip of the tail. The cuticle is smooth and without markings.

To the naked eye the male worm is characterized by its slender dimensions (about 40 mm. in length by 0·1 mm. in diameter), by its marked disposition to curl, and by the peculiar vine-tendril-like tail, the extreme end of which is sharply incurvated (Fig. 110, a). The cloaca gives exit to two slender, unequal spicules (0·2 and 0·6 mm. respectively). The existence of caudal papillæ in the male worm has been ascertained by Leiper. There are in all two rows of fifteen each, extremely minute, mainly arranged around the anus.

The life-span of F. bancrofti and its microfilaria have not been determined. From the fact that the microfilariæ have been found in the blood many years after the opportunity of infection has passed, it is to be concluded that both of them may live for many years. Experiments with the microfilaria of Filaria (Dirofilaria) immitis have shown that in the case of

Fig. 112.—Calcified F. bancrofti lying in and blocking a lymphatic vessel.
(After Bahr.)

this worm the microfilaria may live for at least three years, and in this time acquire somewhat increased dimensions, but it does not follow that the inference from these experiments is applicable to microfilaria bancrofti. I have seen the latter completely disappear from the circulation within a few hours of the death of the parent worm during an attack of lymphangitis. Nothing is known of what becomes of the microfilariæ when they are effete or die.

As shown by Wise and Bahr, the mature worm becomes cretified after its death, and may be found, sometimes in large numbers, in this condition in the lymphatic vessels and glands. (Figs. 112, 113.)

Morbid anatomy and pathology. The filaria not generally pathogenic.—In most cases of filarial infection the parasite exercises no manifest injurious influence whatever. In a certain proportion of instances, however, there can be no doubt that it does have a very prejudicial effect on its host; and this mainly by obstructing lymphatics. The

Fig. 113.—Section of a fibrosed lymphatic gland. (After Bahr.)
A, Portions of a calcified F. bancrofti; B, partially occluded lymphatic vessel.

healthy, fully formed microfilariæ—that is to say, the larval filariæ which, by means of the microscope, we see in the blood—have, so far as we can tell, no pathogenic properties whatever; the parent worm and the immature products of conception, alone, are dangerous.

Filarial disease originating in injury of lymphatic systems.—Roughly speaking, the filaria causes two types of disease: one characterized by varicosity of lymphatics, the other by more or less solid œdema. The exact way in which the parasite operates has not been definitely and absolutely ascertained for all types of filarial disease. Apparently, in some instances, a single worm, or a bunch of worms, may plug the thoracic duct, and act as an embolus or originate a thrombus; or the worm may give rise to inflammatory thickening of the walls of this vessel, and so lead to obstruction from the consequent stenosis or thrombosis. In other instances the minor lymphatic trunks and the glands may be similarly occluded. As an effect of either form of occlusion, the lymphatic areas drained by the implicated vessels are cut off from the general circulation, and varicosifcy or œdema, or both, ensue.

Pathology of lymphatic varix.— In consequence of the rich anastomosis existing between the contiguous lymphatic areas, on filarial obstruction occurring in one of them a compensatory lymphatic circulation is sooner or later established. But before this can be properly effected a rise of lymph pressure and a dilatation of the lymphatics in the implicated area must take place. This leads to lymphatic varix of different kinds, degrees, and situations. When the seat of filarial obstruction is the thoracic duct, the chyle poured into that vessel can reach the circulation only by a retrograde movement; consequently, this fluid may be forced to traverse in a retrograde way the abdominal and pelvic lymphatics, the lymphatics of the groin, scrotum, and abdominal wall. As a consequence, these vessels, together with the thoracic duct up to the seat of obstruction, become enormously dilated. In dissections of such cases (Fig. 114) the thoracic duct has been found distended to the size of a finger, the abdominal and pelvic lymphatics forming an enormous varix, perhaps a foot in diameter and many inches in thickness, concealing kidneys, bladder, and spermatic cords. In such cases, when one of the vessels of the varix is pricked or ruptures, the contents are found to be white or pinkish. They are not limpid like ordinary lymph. They are chyle, therefore—chyle on its way to enter the circulation by a retrograde compensatory track. When the varix involves the integuments of the scrotum, the result is "lymph scrotum"; when most prominent in the groin, then a condition of glands is produced which I have called "varicose groin glands"; when the lymphatics of the bladder or kidneys are affected and rupture from over-distension, then chyluria is the result; when those of the tunica vaginalis rupture,

Fig. 114.—Dissection of the lymphatics in a case of chyluria, showing the dilated right and left renal lymphatics and thoracic duct. (Mackenzie, Trans. Path. Soc. Lond.)

then there is chylous dropsy of that sac—"chylocele"; the same may happen in the peritoneum—chylous ascites. Occasionally varicose lymphatic glands, resembling those frequently encountered in the groins, are found in the axilla. Occasionally, also, limited portions of the lymphatic trunks of the limbs are similarly and temporarily, or more permanently, distended. This, doubtless, is the pathology of all those forms of filarial disease characterized by visible varicosity of lymphatics, with or without lymphorrhagia. It may happen that the obstruction is in some lymphatic tract on the distal side of the entrance of the chyle-bearing vessels into the receptaculum chyli. In this case a rupture of the consequent lymphatic varix will give issue to lymph unmixed with chyle.

Filariœ may disappear from the blood in such cases.— In filarial disease associated with lymphatic varix, micronlariae are generally present in the blood as well as in the contents of the dilated vessels. Sometimes, it is true, the microfilarise are not found. Such cases are probably of long standing; had the microfilaria been looked for at an earlier stage of the disease, it would probably have been discovered. I have watched cases in which the larva has disappeared in this way; though at first found in abundance in the blood, after a year or longer it ceased to appear there. The reason for this disappearance is doubtless the death of the parent parasites, an occurrence I have seen associated with attacks of acute lymphangitis. Although the original cause of the varix may thus disappear, the effect is permanent.

Pathology of elephantiasis arabum. Microfilariœ not usually present in the blood in elephantiasis.— In those cases of filarial disease in which elephantiasis arabum is the leading feature, it is not usual at any stage of the established disease to find microfilarise in the blood or elsewhere, unless it be in countries in which filariasis is extremely common and reinfection, or extensive infection, highly probable.

Reasons for regarding elephantiasis as a filarial disease.— From this circumstance the absence of microfilarise from the blood in elephantiasis— the question naturally arises, Why attribute this disease to the filaria? The answer to this is: (1) The geographical distribution of Filaria bancrofti and of elephantiasis arabum corresponds; where elephantiasis abounds there the filaria abounds, and vice versa. (2) Filarial lymphatic varix and elephantiasis occur in the same districts, and frequently concur in the same individual. (3) Lymph scrotum, an unquestionably filarial disease, often terminates in elephantiasis of the scrotum. (4) Elephantiasis of the leg sometimes supervenes on the surgical removal of a lymph scrotum. (5) Elephantiasis and lymphatic varix are essentially diseases of the lymphatics. (6) Filarial lymphatic varix and true elephantiasis are both accompanied by the same type of recurring lymphangitis. (7) As filarial lymphatic varix is practically proved to be caused by the filaria, the inference that the elephantiasis of warm climates, with rare exceptions —the disease with which the former is so often associated and has so many affinities— is attributable to the same cause, appears to be warranted.

Explanation of the absence of microfilariœ in the blood in elephantiasis.— If the filaria be the cause of tropical elephantiasis, how account for the absence of filaria larvæ in the blood, as is the case in the vast majority of instances of this disease? The answer is: Either the disease-producing filariæ have died; or the lymphatics draining the affected area are so effectually obstructed by the filaria, its products, or its effects, that any microfilarise they may contain, or may have contained, cannot pass along these vessels to enter the circulation. Adult filarise of both sexes in large numbers may be found in enlarged fibrosed lymphatic glands— epitrochlear, for example— without the presence of the corresponding microfilariæ in the blood- stream.

We have already said that in filarial lymphatic varix the parasites which produced the disease may die, particularly during attacks of lymphangitis; we have also seen that they may become cretified and may be found in large numbers in this condition or alive in the glands and lymphatic trunks, where, as Bahr has shown, they give rise to giant-cell formation and-fibrotic changes of an obstructive nature. (Figs. 112, 113.) I do not think, however, that this is the entire explanation of the origin of elephantiasis.

Lymph stasis produced by filaria ova.— I have twice in filariasis found ova of the filaria in lymph; once in the lymph from a lymph scrotum, once in lymph procured by aspirating a varicose groin gland. Therefore, at times, the filaria may produce ova instead of swimming larvæ. The ova of the filaria are not like the long, supple, slim, active, swimming larvae; they are passive, more or less rigid oval bodies nearly five times the diameter of the embryo coiled up in their interior. In consequence of their size and passive character the ova, unlike the normal free-swimming larvae, are quite incapable of traversing such lymphatic glands as, in the event of their escape from the parental worm, they may be carried to passively by the lymph-stream. It is an accepted fact in pathology that an essential element in the causation of elephantiasis is lymph stasis. I have ventured to conjecture that the stasis of lymph which eventuates in tropical elephantiasis is in some instances produced by embolism of the lymphatic glands by ova of the filaria.

If ova are expelled by the parent filaria, it must be as a result of some hurrying of the process of filarial parturition. That this does occur sometimes the discovery, already mentioned, of filaria ova in the lymph fully proves. We can readily understand how, in consequence of mechanical injury, to which from her exposed position in the limbs she must be frequently subjected, or of some other cause, the parent filaria may miscarry. Should this happen, then the contents of her uterus will be expelled prematurely, and before the ova, normally lying at the upper part of her uterus, have become the long, outstretched, active larvae we see in the blood. If a crowd of these passive, massive ova are carried by the lymph -stream to the lymphatic glands of a limb, in the lymphatic trunks of which a female filaria is lying aborting, embolism of the afferent lymphatics of the glands must result and stasis of lymph in the limb ensue.

Inflammation necessary for the production of elephantiasis.— Lymph stasis alone does not produce elephantiasis; this has been proved by experimental ligature of lymphatic trunks. It may produce a form of œdema, but not true elephantoid hypertrophy. Should inflammation occur in an area of lymphatic congestion so produced, as it is very apt to do on the slightest injury, then elephantiasis will supervene; for, unless the lymphatics of an inflamed area are patent, the products of inflammation are not completely absorbed. Erysipelatoid inflammation, frequently recurring, is a well-recognized feature of almost every case of elephantiasis arabum.

Sequence of events in elephantiasis.— The sequence of events in the production of elephantiasis is, I believe, as follows: Parent female filaria in the lymphatic system of the affected part; obstructive fibrotic changes in the glands or lymphatic trunks; or injury of the filaria leading to premature expulsion of ova; and embolism of lymphatic glands supervening on either of these causes of obstruction; stasis of lymph; lymphangitis from subsequent traumatism or other cause (as septic infection) in the congested area; imperfect absorption of the products of inflammation; recurring attacks of inflammation leading to gradual, intermittently progressive, inflammatory hypertrophy of the part.

In this way I explain the production of elephantiasis by the filaria. And in this way I explain the absence from the blood of the larvæ of the parasite which started the disease; they cannot pass the occluded glands. Very likely the parent worm or worms die at an early stage of the disease, killed by the subsequent lymphangitis, or by the cause which led to premature parturition.

The subjects of elephantiasis less liable than others to microfilariœ in the blood.— Some years ago I made a curious observation which supports the view just stated. I received from Surgeon-Major Elcum 88 slides of night blood from 88 natives of Cochin. Of these 88 persons, 14 were affected with elephantiasis, 74 were not so affected. Of the slides coming from the 74 non-elephantiasis cases, 20 contained microfilariæ, one in every 3½; of the 14 elephantiasis cases, only 1 had microfilariae. Why should the elephantiasis cases have proportionately fewer microfilariæ than the non-elephantiasis cases? The answer may be, that in the former the existence of elephantiasis implied that a large area of their lymphatic systems was blocked, and the blood could be stocked with microfilariæ carried by the lymph from only a relatively small lymphatic area; and that there was, therefore, a proportionately lesser likelihood of the presence of parent filariæ having for their young an unobstructed passage to the blood.

FILARIAL DISEASES

Enumeration of the filarial diseases.— The diseases known to be produced by Filaria bancrofti are abscess; lymphangitis; arthritis; synovitis; abscess of hip-joint; varicose groin glands; varicose axillary glands; lymph scrotum: cutaneous and deep lymphatic varix; orchitis; funiculitis; chyluria; elephantiasis of the leg, scrotum, vulva, arm, mamma, and elsewhere; chylous dropsy of the tunica vaginalis; chylous ascites; chylous diarrhœa, and probably other forms of disease depending on obstruction or varicosity of the lymphatics, or on death of the parent filariæ, including peritonitis and secondary infection by pyogenic microorganisms (Wise and Minett).

Abscess.— Occasionally, as already mentioned, whether in consequence of blows or other injuries, of lymphangitis, or of unknown causes, the parent filarise die. Generally the dead body is absorbed, just as a piece of aseptic catgut would be, or becomes cretified.*[8] Sometimes the dead worm acts as an irritant and causes abscess, in the contents of which fragments of the filaria may be found. Such abscesses, occurring in the limbs or scrotum, will discharge in due course, or may be opened; if properly treated surgically they may lead to no further trouble. Should they form in the thorax or abdomen, serious consequences and even death may ensue.

Probably, in certain instances, abscess forms at times independently of the death of the parasite; e.g. in varicose glands, in lymph scrotum, in elephantiasis. The death of the parent filaria is apt to be lost sight of as a possible cause of abscess in the subjects of filarial infection. Deep-seated pain in the thorax or abdomen, with inflammatory fever followed by hectic, and a diminution in the number of microfilariæ in, or their entire disappearance from, the peripheral blood, should in such circumstances suggest a diagnosis of filarial abscess and indicate exploration and, if feasible, active surgical interference.

Lymphangitis and elephantoid fever. Symptoms.— Lymphangitis is a common occurrence in all forms of filarial disease, particularly in elephantiasis, varicose glands, and lymph scrotum. When occurring in the limbs the characteristic painful, cord-like swelling of the lymphatic trunks and associated glands, and the red congested streak in the super jacent skin, are usually apparent at the commencement of the attack. Very soon, however, the connective tissue and skin of the implicated area become inflamed and tense, and high fever, preceded by severe and prolonged rigor, sets in. The attack may continue for several days, and be accompanied by severe headache, anorexia, often vomiting, and sometimes delirium. After a time the tension of the inflamed integuments may relieve itself by a lymphous discharge from the surface. Usually the attack ends in profuse general diaphoresis. The swelling then subsides gradually though not entirely. Lymphangitis may be confined to groin glands, testis, spermatic cord, or abdominal lymphatics. When it affects an extensive abdominal varix, symptoms of peritonitis are rapidly developed and may prove fatal.

Diagnosis.— This fever, appropriately named by Fayrer " elephantoid fever," occurs habitually at varying intervals of weeks, months, or years, in nearly all forms of elephantoid disease. Its tendency to recur, the severe rigor ushering it in, and the terminal diaphoresis cause it to be mistaken for ague. In Barbados, where there is no malaria, it is habitually called " ague." The implication of the lymphatics, the local pain, the erysipelatoid redness and swelling, the prolonged pyrexial stage, the absence of the malaria parasite from the blood, the presence there very possibly of microfilariæ, and the powerlessness of quinine to control the fever, suffice for diagnosis. Nevertheless, error in diagnosis is common, particularly when the attacks recur frequently and with a certain degree of regularity, as is usually the case.

Treatment.— The treatment should consist in removing any cause of irritation, in rest, elevation of the affected part, cooling lotions or warm fomentations, mild aperients, opium or morphia to relieve pain, and, if tension is great, pricking or scarifying the swollen area under suitable aseptic conditions. Subsequently the parts, if their position permits, should be elevated and firmly bandaged.

Varicose groin glands (Figs. 115, 116).— Varicose groin glands are frequently associated with lymph scrotum, with chylous dropsy of the tunica vagiualis, or with chyluria. Occasionally all four conditions coexist in the same individual.

Symptoms.— As a rule the patient is not aware of the existence of these varicose glands until they have attained considerable dimensions. Then, a sense of tension, or an attack of lymphangitis, calls attention to the state of the groins, where certain soft swellings are discovered. These swellings may be of insignificant dimensions or they may attain the size of a fist. They may involve both groins, or only one groin; they may affect the inguinal glands alone, or the femoral glands alone, or (and generally) both sets together.

To the touch they feel soft, doughy, and obscurely lobulated. The skin, natural in appearance, can be glided over the surface, but the swellings themselves are not movable over the subjacent fascia. Occasionally hard, kernel-like pieces can be felt in their interior, or the entire mass may be more or less indurated. On thrusting a hypodermic needle into the swellings, white or reddish chylous, or clear lymphous fluid can be aspirated, sometimes in great abundance. This fluid coagulates rapidly, and usually contains living microfilariæ or filarial ova. Diagnosis.—It is important to be able to diagnose these tumours from hernia, for which they are often mistaken. This can be done by observing that they are not tympanitic on percussion; that though pressure causes them to diminish, they do so slowly; that there is no sudden dispersion accompanied by gurgling, as in hernia, on taxis being employed; that they convey

Fig. 115.—Varicose groin glands and chylocele. (From a patient under the care of Mr. Johnson Smith.)

a relatively slight or no impulse on coughing; that they slowly subside on the patient lying down, and slowly return, even if pressure be applied over the saphenous or inguinal openings, on the erect posture being resumed. The cautious use of the hypodermic needle will confirm diagnosis; which would be further strengthened by the coexistence of lymph scrotum, chyluria, or chylous hydrocele, and the presence of filariæ in the blood. Chronic swellings about the groin, cords, testes, and scrotum in patients from the tropics should always be regarded as being possibly filarial.

Pathological anatomy.—On dissection these tumours are found to consist of bunches of varicose lymphatics, and, it may be, to form part of a vast lymphatic varix involving the pelvic and abdominal lymphatics.

Treatment.—Unless they give rise to an incapacitating amount of discomfort, and are the seat of frequent

Fig. 116—Unusually large varicose groin glands. (From photograph, Journ. of Trop. Med.)

attacks of lymphangitis, varicose groin glands are best left alone. It must always be remembered that they are part of an anastomosis necessary to life. Should they be very troublesome and incapacitate for work, they may be removed. In operating, strict aseptic methods must be practised, as septic lymphangitis readily occurs, and has frequently proved fatal after operations in such cases. Excision is not always satisfactory, as it may be followed by lymphorrhagia at the seat of the wound, by excessive dilatation of some other part of the implicated lymphatic area, by chyluria, or by elephantiasis in one or both legs.

I have suggested that these tumours might be treated by establishing an anastomosis between one of the dilated lymphatic vessels and a neighbouring vein. Sir Rickman Godlee has twice performed such an operation for me with partial success: it is somewhat difficult, owing to the fragile nature of the dilated lymphatic vessels, and the shortness of their course.

It is said (Azema) that these glands tend to diminish in size after the age of 40. I cannot confirm this statement from personal observation.

Similar varicose dilatation of the axillary glands is sometimes, though much more rarely, found. Bancroft designated these varicose axillary and groin glands "helminthoma elastica."

Cutaneous and deeper lymphatic varices.— Occasionally cutaneous lymphatic varices are seen on the surface of the abdomen, on the legs, arms, and probably elsewhere. Sometimes they are permanent; sometimes, when more deeply situated, they constitute little swellings which come and go in a few hours. I believe these latter often depend on the actual presence of parent filariæ in the tumour. Such varices are evidence of lymphatic obstruction. Filarial lymphangiectasis of the spermatic cord is not uncommon. The contents may be milky and chylous, or straw-coloured and lymphous, according to situation and connections.

Thickened lymphatic trunks.— Maitland has frequently seen in Madras cases of lymphangitis in which, after the initial swelling and inflammation had subsided, a line of thickening remained. On excising this thickened tissue and carefully dissecting it, he has found minute cyst-like dilatations of the lymphatic involved, and in these cysts, coiled up, adult nlarise, sometimes dead, sometimes a,live. The lymphangitis, he believes, is caused in these cases by the death of the filarise. Daniels has made similar observations in British Guiana. Such a case I saw under the care of Dr. Abercrombie at Charing Cross Hospital in London. On the subsidence of a filarial lymphangitis of the arm a thickening, about the size of a finger-tip, remained on the forearm. Believing that it contained adult filariæ, this thickening was excised by Mr. Young and placed in normal salt solution. Eight hours later the mass was carefully dissected, and a living female filaria, about 4 in.

Fig. 117.—Lymph scrotum and varicose groin glands. (Photograph by Dr. Rennie, Foochow.)

in length, was turned out. The parasite continued to live and swim about actively in the salt solution for nearly two hours. Bahr has called attention to the frequency with which the epitrochlear gland is enlarged and thickened by filarial invasion.

Lymph scrotum (Fig. 117). Symptoms.—In this disease the scrotum is more or less enlarged. Though usually silky to the touch, on inspection the skin presents a few, or a large number of, smaller or larger lymphatic varices which, when pricked or when they open spontaneously, discharge large quantities of milky, or sanguineous - looking, or straw-coloured, rapidly coagulating lymph or chyle. In some cases 8 or 10 oz. of this substance will escape from a puncture in the course of an hour or two; it may go on running for many hours on end, soiling the clothes of the patient and exhausting him. Usually microfilariæ can be discovered in the lymph so obtained, as well as in the blood of the patient. In a large proportion of cases of lymph scrotum the inguinal and femoral glands, either on one or on both sides, are varicose.

Probably provoked by friction against the thighs and clothes, erysipelatoid inflammation and elephantoid fever are frequent occurrences. Abscess is not uncommon. In time, in a proportion of cases, the scrotum tends to become permanently thickened and to pass into a state of true elephantiasis.

Treatment.— Unless inflammation be a frequent occurrence, or there be frequent and debilitating lymphorrhagia, or unless the disease tend to pass into true elephantiasis, lymph scrotum— kept scrupulously clean, powdered, suspended, and protected— had better be left alone. Should, however, for these or other reasons, it be deemed expedient to remove the diseased tissues, this can be effected easily. The scrotum should be well dragged down by an assistant whilst the testes are pushed up out of the way of injury. A finger knife is then passed through the scrotum, and in sound tissues, just clear of the testes, and the mass excised by cutting backwards and forwards. No diseased tissues, and hardly any flap, should be left. Sufficient covering for the testes can be got by dragging on and, if necessary, dissecting up the skin of the thighs, which readily yields and affords ample covering. It is a very common but a very great mistake to remove too little. As a rule, the wound, if carefully stitched and dressed antiseptically, heals rapidly. In consequence of this violent interference with a large varix, of which that in the scrotum is but a part, chyluria, or elephantiasis of a leg, may supervene. The patient should be warned of this possibility.

Chyluria. Pathology.— When a lymphatic varix in the walls of the bladder, or elsewhere in the urinary tract, the consequence of filarial obstruction in the thoracic duct or in the lymphatics of the urinary system, ruptures, there is an escape of the contents of the lymphatics into the urine. Chyluria, or lymphuria, is the result.

Symptoms.— This disease frequently appears without warning; usually, however, pain in the back and aching sensations about the pelvis and groins probably caused by great distension of the pre-existing lymphatic varix— precede it. Retention of urine, from the presence of chylous or lymphous coagula, is sometimes the first indication of serious trouble. Whether preceded by aching, or by retention, or by other symptoms, the patient becomes suddenly aware that he is passing milky urine. Sometimes, instead of being white, the urine is pinkish or even red; sometimes, white in the morning, it is reddish in the evening, or vice versa. Sometimes, whilst chylous at one part of the day, it is perfectly limpid at another. Great variety in this respect exists in different cases, and even in the same case from time to time, depending on temporary closure of the rupture in the lymphatic, and also on the nature of the food.*[9]

Physical characters of chylous urine.— If chylous urine be passed into a urine glass and allowed to stand, as a rule, within a very short time, the whole of the urine becomes coagulated. Gradually the coagulum contracts until, at the end of some hours, a small, more or less globular clot, usually bright red or pinkish in colour, is floating about in a milky fluid. Later, the milky fluid separates into three layers. On the top there is formed a cream-like pellicle; at the bottom a scanty reddish sediment, sometimes including minute red clots; in the centre the mass of the urine forms a thick, "intermediate stratum, milky white or reddish white in colour, in which floats the contracted coagulum, If a little of the sediment be taken up with a pipette and examined with the microscope, it is found to contain red blood-corpuscles, lymphocytes, granular fatty matter, epithelium, and urinary salts, and mixed with these in a large proportion of cases, though not in all, microfilariæ. The middle layer contains much granular fatty matter; whilst the upper cream-like layer consists of the same fatty material in greater abundance, the granules tending to aggregate into larger oil globules. If a little of the coagulum be teased out, pressed between two slides, and examined with the microscope, microfilariæ, more or less active, may be found in the meshes of the fibrin. If ether or xylol be shaken up with the milky urine, the fat particles are dissolved out and the urine becomes clear; the fat may be recovered by decanting and evaporating the ether which floats on the urine. Boiling the urine throws down a considerable precipitate of albumin. When the urine contains only lymph, fatty elements are absent, or are present in but very small amount.

Recovery and relapse.— Chyluria comes and goes in a very capricious manner. Sometimes the urine remains steadily chylous for weeks and months, and then suddenly, without obvious cause, becomes limpid and natural-looking, and free from fat or albumin. Later a relapse will occur, again to disappear after an uncertain time; and so on during a long course of years.

Retention of urine. Retention of urine is nob an unusual occurrence; it is produced by the formation of coagulum in the bladder. The retention usually gives way after a few hours of distress, worm-like clots being passed.

Constitutional effects.— Although chyluria is not directly dangerous to life, yet, being prolonged, it gives rise to pronounced anæmia, with depression of spirits, and feelings of weakness and debility, and thus tends to incapacitate the patient for active, vigorous life.

Exciting causes of chyluria.— Chyluria is very liable to occur, either for the first time or as a relapse, in pregnancy or after childbirth; the disturbance of the pelvic lymphatics in pregnancy and the muscular efforts attending labour apparently causing rupture of pelvic lymphatics previously rendered varicose by filarial obstruction of the thoracic duct. In men, running, leaping, and violent efforts generally are sometimes assigned as its cause; usually the exciting cause is not discoverable.

Treatment.— The treatment of chyluria should be conducted on the same lines as the treatment of inaccessible varix elsewhere; that is to say, by resting and elevating the affected part, and thereby diminishing as far as possible the hydrostatic pressure in the distended vessels. Many forms of medicinal treatment have been advocated. Because during treatment with some drug a chyluria has subsided, curative properties are apt to be attributed to the drug. The best results are got by sending fhe patient to bed, elevating the pelvis, restricting the amount of food and fluid especially fatty food gentle purgation, and absolute rest. It will be found that a day or two of treatment on these lines is often followed by temporary, perhaps prolonged, cessation of the chyluria. The drugs which have been particularly lauded in the treatment of this disease are gallic acid in large doses, benzoic acid in large doses, glycerin, the tincture of the perchloride of iron, decoction of mangrove bark, chromic acid, quinine, salicylate of soda, ichthyol, and Nigella sativa. I do not believe that these substances have any influence whatever in stopping the lymphorrhagia. Neither do I believe that thymol, recommended by Lawrie, or methylene blue, recommended by American writers, has any effect either on the filaria or on the disease it gives rise to; since their first recommendation both drugs have been tried, but in other hands-have failed. Filarial orchitis.— Several French writers describe under the name " malarial orchitis " a special form of inflammation of the testes, and here and there in Indian medical literature allusion is made to the same or a similar subject. " I have many times seen filarial orchitis, but I cannot say I have seen orchitis of purely and unquestionably malarial origin. The fever attending filarial orchitis which is usually associated with lymphangitis of the spermatic cord (funiculitis) and perhaps with inflammation of the scrotum like ordinary elephantoid fever resembles very closely a malarial attack, and may be mistaken for this. Without absolutely denying the existence of such a disease as malarial orchitis, I would suggest that the affection described by the French and Indian writers referred to, and endemic inflammations of testes, spermatic cords, and scrotum generally, are of filarial origin.

Filarial synovitis.— Maitland mentions acute synovitis of the knee-joint as one of the filarial diseases, and gives the particulars of five cases. He considers the concurrence of synovitis with filarial invasion too common to be accidental. Bahr has confirmed this, and has found that ankylosis often results. In cases where the hip- joint is affected, removal of the inflamed iliac glands draining the area appears to relieve the condition.

ELEPHANTIASIS

Its prevalence.— Elephantiasis is by far the most frequent manifestation of filarial invasion, and is exceedingly common in some of the endemic districts. Thus, in certain districts in Cochin about 5 per cent, of the population, in Samoa about every second individual, in Huahine seven-tenths of. the adult male population are affected. In many other tropical and sub-tropical countries, if not so common as in those just mentioned, elephantiasis is, nevertheless, common enough.

Parts affected.— In 95 per cent, of the cases the lower extremities— either one or both— alone, or in combination with the scrotum or arms, are the seat of the disease. The foot and ankle only, or the foot and leg, or the foot, leg, and thigh, may, each or all, be involved. The scrotum is also a common situation for elephantiasis. The arms are more rarely attacked; still more rarely the mammæ, vulva, and circumscribed portions of the integuments of the limbs, trunk, neck, or scalp (Fig. 118).


Fig. 118.—Elephantiasis of scalp. (Journ. of Trop. Med.)
The recurring erysipelatoid attacks.—The disease in any of these situations commences with a rapidly evolved lymphangitis, dermatitis, and cellulitis accompanied by elephantoid fever. On the subsidence of the acute symptoms the skin and subcutaneous fascia of the affected part do not quite resume their original proportions; the inflammatory effusion not being completely absorbed, some permanent thickening remains. Recurrences of this inflammation once or twice a month, or perhaps once in six months, or every twelve months, or even at longer intervals, add a little each time to the bulk of the limb or scrotum. Thus, gradually, an enormous swelling may be built up. Occasionally, though very rarely, enlargement may progress after one, two, or more initial inflammatory attacks, and without further recurrence of these.

Clinical characters of the swelling.—The affected part is greatly increased in bulk. The surface of the skin, in confirmed elephantiasis especially, is rough and coarse; the mouths of the follicles are sometimes unusually distinct; the papillæ and glands are either hypertrophied or atrophied; the hair is coarse and sparse; the nails are rough, thick, and deformed. Around joints the thickened integuments are thrown into folds, the comparatively smooth-sided and deep interlying sulci permitting limited movement. There is no distinct line of demarcation between healthy and diseased skin. The implicated integuments are hard, dense, pit but slightly if at all on pressure, and cannot be pinched up or freely glided over the deeper parts.

Its macroscopic anatomy.— On cutting into the swelling, the derma is found to be dense, fibrous, and enormously hypertrophied. The subjacent connective tissue is increased in bulk, having, especially in the case of the scrotum, a yellowish, blubbery appearance from lymphous infiltration. A large quantity of fluid wells out on division of such tissues. The muscles, nerves, and bones are not necessarily diseased, although in rare instances they may be degenerated and slightly or considerably atrophied from pressure. The blood-vessels are large; the lymphatics dilated; the associated lymphatic glands, both of the same side and, very often, of the opposite side, enlarged and dense.

True elephantiasis permanent.— Though in recent cases the bulk of -the limbs may be much reduced temporarily by treatment, the disease is never permanently recovered from. Simple lymphatic œdema in areas which have never become inflamed subsides readily enough on pressure or elevation.

Elephantiasis of the leg (Fig. 119). Elephantiasis of the lower extremities is usually, though by no means always, confined to below the knee. The, swelling may attain enormous dimensions and involve the entire extremity, the leg or legs attaining a circumference, in aggravated cases, of several feet.

Treatment.— In the treatment of elephantiasis of the leg the patient should be encouraged to persevere with elastic bandaging, massage, and elevation of the limb. Castellani claims good results from a combination of these measures with daily injections of fibrolysin 2 c.c. Ligature of the femoral artery has been practised; it is probably useless, and is certainly not a justifiable method of treatment. Sometimes, in extreme cases, good results are got from excision of redundant masses of skin, a longitudinal strip of three or four inches in breadth by a foot or more in length being dissected off. Charles advocates complete resection of the whole of the elephantoid tissue except the sole of the foot, followed by extensive skin-grafting. Electrolysis and mercury have also been used; I question their value. During the acute attacks, tension may be relieved by aseptic punctures with a sharp lancet. At all times the limb must

Fig. 119.—Elephantiasis of legs; scrotum and right arm also affected. (Photograph by Dr. Turner, Samoa.).

be carefully guarded from injury, and shoes and trousers worn. Slight injuries provoke the inflammatory recurrences. Wading in water, prolonged standing, violent exercise, and exposure to a hot sun are injurious and should be avoided.

Handley has brought forward an operation, lymph-angioplasty, the underlying principle of which is the drainage of an area of lymph stasis into an adjacent patent lymphatic area by means of strands of silk passing from one to the other. He describes the operation thus: " Eight stout silk threads were led upwards from the foot to a point in the iliac fossa just above Poupart's ligament. These were spaced out round the limb at intervals. Above they united to form a leash. The iliacus muscle was exposed by a short incision like that for ligature of the external iliac artery. Half the threads were passed through a portion of the iliacus muscle, and were knotted in pairs to the other four threads, thus fixing them securely to the tissues of the iliac fossa. The multiple small incisions through which the threads were introduced were closed by horsehair sutures, leaving the silk completely buried in the subcutaneous tissues." He claims a comparative success in one marked case of elephantiasis of the leg. Judging from the narrative of this case (Trans. Soc. of Trop. Med., vol. ii., p. 41) the operation is attended with considerable risk from sepsis. Others who have practised it do not report favourably on the results.

Lanz's operation aims at deep lymphatic drainage. A longitudinal incision is made through the fascia lata down to the femur, the periosteum of which is stripped and the bone trephined in several places; strips of fascia are then inserted into the openings thus made. Surgeons who have followed this method report excellent results; many have omitted trephining the bone and have contented themselves with incising the fascia lata.

Kondoleon's operation consists also of free incision of the fascia lata and removal of large sections of the aponeurosis; the removal of this tissue assists in the anastomosis of lymph channels and veins. This operation has been favourably reported on by Matas.

Elephantiasis of the scrotum (Fig. 120). Weight of tumours.— Elephantiasis of the scrotum, or "scrotal tumour" as it is sometimes called, may attain an enormous size: 10, 15, or 20 lb. are common weights for these tumours, and 40 or 50 lb. is by no means uncommon. The largest recorded weighed 224 lb.

Anatomical characters.—There are certain points in the anatomy of scrotal tumour which the operating surgeon must bear in mind. These tumours consist of two portions (Fig. 121): first, a dense rind of hypertrophied skin (A e), thickest towards the lower part and gradually thinning out as it merges above into the sound skin of the pubes, perineum, and thighs; second, enclosed in this rind, a mass of lax, blubbery,

Fig. 120.—Elephantiasis of scrotum; left leg slightly affected.
(Photograph by Dr. Turner, Samoa.)

dropsical, easily-torn-through, areolar tissue in which testes, cords, and penis are embedded. The shape of the tumour is more or less pyriform. The upper part, or neck, on transverse section (B) is triangular, the base (B k) of the triangle being in front, the apex (B j)—usually somewhat bifid from dragging on the gluteal folds—towards the anus, the sides (B h) towards the thighs. In the latter situation the skin, though usually more or less diseased, is, from pressure, softer and thinner than elsewhere, tempting the surgeon to utilize it for the formation of flaps—not always a wise proceeding. The penis (A a, B f) always lies in the upper and fore part of the neck of the mass; it is firmly attached to the pubes by the suspensory ligament. The sheath of the penis is sometimes specially hypertrophied, standing out as a sort of twisted ram's-horn-like projection on the anterior surface of the tumour; this, however, is unusual. Generally the sheath of the penis is incorporated in the scrotal mass, the prepuce being dragged on and inverted so as to form a long channel leading to the glans penis and opening (A l) half-way down, or even lower, on the face of the tumour. The testes (A c), buried in the central blubbery tissue, usually lie towards the back of the tumour, one on each side, in large tumours generally nearer the lower than the upper part. They are more or less firmly attached to the under part of the scrotum by the hypertrophied remains of the gubernaculum testium (A d)—a feature to be specially borne in mind by the surgeon. As a rule both testes carry large hydroceles with thickened tunicæ vaginales. The spermatic cords also (A b, B g) are thickened and greatly elongated. The arteries supplying these enormous growths are of considerable size; the vein's, too, are very large, and, as they permit regurgitation of blood from the trunk, are apt to bleed freely.


Fig. 121.—Diagram of anatomy of elephantiasis of scrotum. (For reference, see text.)

Their importance.—Beyond inconvenience caused by their weight, the presence of the cumbersome mass between the legs, the suffering attendant on recurring attacks of inflammation and elephantoid fever, the sexual disability, and the unsightliness, these tumours are not of great importance; they do not, as a rule, directly endanger life. They may grow rapidly or slowly; they may attain a large size in two or three years, or they may be in existence for years and at the end of this time amount to little more than a slight thickening of the scrotum. Occasionally, in large tumours, portions of the mass become gangrenous, or abscess may form, and in these ways life may be endangered.

Treatment.—Scrotal tumour, as soon as it becomes unsightly or inconvenient, should be removed. Often, after thorough removal of all the diseased integuments, elephantoid fever, which before may have been frequent, ceases to recur.

Treatment preliminary to operation.— If the tumour is of considerable size, the patient should keep his bed for a day or two before operation, the mass being suspended so as to drain it of fluid and blood. It is thus rendered lax, and the operator is enabled to ascertain by palpation the position of the testes and, if such chance to be present, of hernia a not very unusual complication. The possibility of undescended testes should not be overlooked.

Operation.— Before making provision for the prevention of hæmorrhage the operator should mark out by shallow cuts the line at which he proposes to separate the tumour, care being taken that these guiding incisions run through and include only absolutely sound skin. If the latter precaution be neglected, disease is very liable to recur in the scar or flaps. First, the tumour is turned up and a shallow transverse cut is drawn in sound skin across the perineum in front of the anus. The tumour being allowed to fall down, a similar shallow cut is made across the pubes. The corresponding extremities of these two cuts are then united either by a straight cut or, if there be a little sound skin on the thigh aspects of the tumour, by semilunar incisions.

Assistants then firmly draw down the scrotum as far as possible, and the surgeon, if he deem it desirable, applies elastic webbing over the mass so as to expel the blood it contains. Next, a stout rubber cord is wound, figure-of-eight fashion, round the neck of the tumour, well above the guiding incisions, and over the pelvis, and firmly secured (McLeod) (Fig. 122). Or the rubber cord is wound round the neck of the tumour only, being kept in place by four strips of bandage passing under this cord, one on each side of the scrotum before and behind, and firmly tied over another strip of bandage encircling the waist.

The testes and spermatic cords are first dissected out through long perpendicular incisions made in front, the remains of the gubernacula testes being hooked up with the finger and snipped through with scissors. The channe of the prepuce is next slit up, the incision being carried up to the pubic limiting mark. The penis can then be shelled out, the prepuce being first cut through around the corona glandis. If lateral flaps can be formed of sound skin they are then dissected up. The perineal and pubic incisions are now deepened and, assistants holding the testes and penis well out of the way, the neck of the tumour is cut through close to the perineum and pubes. Gaping vessels are all carefully ligatured, redundant tunica vaginalis—if hydroceles be present—being excised. The rubber cord is then removed.

Fig. 122.—Rubber cord in position. (McLeod.)

When hæmorrhage has been controlled, the posterior halves of the flaps are brought together by sutures, the anterior halves being united over the testes to the pubic cut. The penis will therefore emerge from the point where the horizontal line meets the perpendicular line of what is now a T- or Y-shaped wound. If no flaps have been made, the testes may be fixed by stitching any tag of tissue connected with them to the perineum, and the dimensions of the wound reduced as much as possible by stitching up the corners at the pubes and perineum.

In dressing it is of importance that the raw surfaces be covered by some aseptic non-fibrous protective—such as oiled silk—before the antiseptic dressing is applied. A fibrous dressing next the raw surfaces is troublesome, as it sticks to the wound and is painful and difficult to remove. The dressing should be massive, well padded, and kept in place by an eight-tailed bandage secured in front and behind to a strap round the waist, a hole being cut in front for the penis to emerge. The large wound generally does well. Skin grafting should be practised freely and early, especially round the root of the penis.

Mortality from operation.—The mortality from these formidable-looking operations, if they are carefully

Fig. 123.—Elephantiasis of labia majora. (After Nuñez.)

done, is small, and need not exceed 5 per cent. The results are very satisfactory, as a rule, the functions of the organs being retained or restored.

Elephantiasis of the arms.—This is comparatively rare. Allowing for the differences between the upper and lower extremities as regards gravitation of fluids, the symptoms and pathology of elephantiasis of the arm are the same as those of elephantiasis of the legs. Beyond the judicious employment of massage and elastic bandaging, little can be done in the way of treatment.

Elephantiasis of the vulva and mammæ.—Elephantiasis of the vulva (Figs. 123, 124) and mammæ (Fig. 125) is still rarer. Where growth has

Fig 124.—Elephantiasis of vulva. (Photograph by Dr. Walter H. B. Macdonald.)

Fig. 125.—Elephantiasis of mammæ; left leg and foot also affected.
(Photograph by Dr. Davies, Samoa.)

become inconveniently large the diseased tissues should be removed. Instances are on record in which the integuments of the mammæ have become so thickened, heavy, and elongated that the organ has descended to the pubes and even to the knee. One such tumour weighed 21 lb. after removal. Tumours of the labia or of the clitoris, similarly, may attain a great size—8 or 10 lb., or even more.

Fig. 126.—Pedunculated groin elephantiasis. (Photograph by Dr. Daniels.)

Elephantiasis of limited skin areas.—Corney states that pedunculated elephantoid tumours, springing from the groin or from the anterior surface of the thigh, are not uncommon in Fiji. One such tumour which he removed weighed 20 lb. Daniels has seen, both in Fiji and in Demerara, several cases of this description (Fig. 126). Silcock describes a pedunculated tumour of this nature that he removed from the neck of an East Indian, and which weighed, after removal, 30 lb. I have often seen limited areas of elephantoid thickening of the skin, particularly on the thighs. These conditions are easily dealt with by simple operations.

Chylous dropsy of the tunica vaginalis, and of the peritoneum; chylous diarrhœa.— Chylous dropsy of the tunica vaginalis is not an unusual occurrence in the tropics. A fluctuating swelling of the tunica vaginalis, which does not transmit light, and which is associated possibly with lymph scrotum, with varicose groin glands, with chyluria, or with microfilariæ in the blood, would suggest a diagnosis of this condition. These collections of chylous fluid in the tunica vaginalis generally contain enormous numbers of microfilariæ. Large numbers of cretified adult filariæ have been found in the thickened tunica vaginalis and in the epididymis in this condition.

These chyloceles may be treated as ordinary hydroceles, either by aseptic incision or by injection.

Filarial orchitis with effusion into the tunica vaginalis, according to Maitland, is best treated by incision of the tunica vaginalis, turning out any clot that may be found in the sac, and stuffing the latter with iodoform gauze. This procedure, he says, gives immediate relief.

Chylous dropsy of the peritoneum and chylous diarrhœa of filarial origin are very rare.

Prophylaxis of filarial disease.— The prevention of filarial disease resolves itself into antimosquito measures and protection from mosquito bite. With this in view, unprotected wells, tanks, or stagnant pools must not be permitted in the neighbourhood of dwelling-houses. The influence of these in spreading filarial disease has been ably demonstrated by Daniels in Demerara, and by Low in Barbados. All vessels used for storing water should be emptied at least once a week. The mosquito net is indispensable in filarial as well as in malarial countries.

The subjects of filariasis should be regarded as dangers to themselves and to the community and be compelled to sleep under mosquito nets. Filaria perstans, Manson, 1891. (Plate X., Fig. 2.)

Synonym.Acanthocheilonema perstans, Railliet, Henry, and Langeron, 1912.


Fig. 127.—Tail of adult F. perstans.
Geographical range.This parasite is very common in the blood of the natives of large districts in tropical Africa. I have found it in natives from Old Calabar and from the basin of the Congo—both in the coast negroes and in those from the interior. Annett, Button, and Elliot report its presence in many places in Southern Nigeria, in Northern Nigeria, in Lagos, in the Gold and Ivory Coasts, in the Kroo Coast, and in Sierra Leone. In Northern Rhodesia it is very common; I found it in 30 per cent. of a number of the natives whom I examined. On the Congo in parts it occurs in half the population. Prof. Firket, of Liége, has confirmed this observation as regards the Congo district. Cook, Hodges, and Low have found the parasite to be extremely common in Uganda, where, in some districts, Low has found it in 90 per cent. of the population. Sometimes it occurs along with mf. loa, mf. bancrofti, and, in British Guiana, as stated, with mf. ozzardi, in the same individual. I have never found it in West Indian negroes, nor, in fact, in natives of any country except those of tropical Africa, and in the aborigines of Demerara. I have frequently found it in Europeans who had resided on the Congo.

Its characters.Microfilaria perstans observes no periodicity, being present in the blood both by day and by night. In this respect it resembles mf. demarquaii and mf. ozzardi; and, like these, in size, shape, and anatomical detail it differs very materially from mf. bancrofti and mf. loa. The number of microfilariæ in the peripheral circulation may vary considerably, but there is no marked difference between day and night. Their special seat of selection is not the peripheral blood, but that of the heart, lungs, aorta and other large vessels. They have not been found in the spleen, and only rarely in the liver and pancreas.

The larva in the blood measures, on an average, 0·2 mm. in length by 0.0045 mm. in breadth; but, as it possesses in a remarkable degree the power to elongate and to shorten itself, these measurements do not always apply. It is manifestly much smaller than mf. bancrofti and mf. loa, and is further distinguished from these microfilariæ by the entire absence of a sheath, and by the characters of its caudal end, which is invariably truncated and abruptly rounded off. The taper which terminates in the tail extends through quite two-thirds of the entire length of the animal. Further, if the head be carefully observed with a high power, a fang can generally be easily seen— much more easily than the corresponding structure in mf. bancrofti— in constant play, shot out and retracted. The V spot is about 0.03 mm. from the cephalic extremity. There is no marked tail spot. No hooked cephalic prepuce can be made out. According to Fülleborn, no red staining " granular mass " can be demonstrated as in the case of mf. bancrofti and mf. loa. Its movements also differ from those of mf, bancrofti, for it not only wriggles about, just as that parasite does, but it indulges in long excursions through the blood, moving freely all over the slide, locomoting in fact very much in the same way as mf. bancrofti does in the mosquito's stomach after it has cast its sheath.

Adult form.— The adult form, discovered by Daniels in Demerara Indians, and subsequently identified by myself as that of F. perstans, is, like F. bancrofti, a long, cylindrical filiform nematode. The body is smooth, without markings; the mouth simple and unarmed. The tail in both sexes is peculiar and characteristic; it is incurvated, and the chitinous covering at the extreme tip is split up as it were into two minute triangular appendages, giving it a mitred appearance (Fig. 127). The adult female measures 70 to 80 mm. in length by 0.12 mm. in breadth. The head is club-shaped and measures 0.07 mm. in diameter. The genital pore opens at 0.6 mm. from the head. The anus opens at the apex of a papilla situated in the concavity of the curve formed by the tail. The diameter of the tail just before termination is 0.02 mm. The male is smaller than the female; it measures 45 mm. in length by 0.06 mm. in breadth. The diameter of the head is 0.04 mm. Close to the opening of the cloaca there are four pairs of preanal and one pair of postanal papillae, and, according to Leiper, another small pair are situated midway between these groups. Two unequal spicules may sometimes be seen protruding from the cloaca. So far the adult forms have been found only in the connective tissues at the root of the mesentery, behind the abdominal aorta, and beneath the pericardium.

Life-history.—Very little is known of the life-history of F. perstans. Although it has a wide geographical range, this filaria appears to be limited in its topography to areas covered by dense forest growth and abounding in swamps. In Kavirondo, where the forest disappears and the land is covered with scrub and short grass, it is not found; likewise it is not found on the grassy plains of the highlands of British East Africa. Towns and cultivated areas are free from it. This peculiar limitation of its distribution would indicate an intermediary restricted to similar stations, certain Tabanidæ, for instance, or certain species of sylvan mosquitoes. In order to find the intermediary host of F. perstans, Low made numerous experiments with many different species of mosquitoes (Culex fatigans, C. atratus, C. viridus, C. Inteolateralis, C. quasigelidus; Anopheles argyrotar sis, A. costalis, A. funestus; Stethomyia nimbus; Janthinosoma musica; Mansonia africana; Uranotœnia cœruleocephala; Tœniorhynchus fuscopennatus) and other blood-sucking insects (Pulex irritans, Sarcopsyila penetrans, Pediculus capitis, and P. vestimentorum). These insects were either caught in the huts of infected persons or were reared from the larva and then fed on infected persons. After a certain time they were dissected, but, with one exception, the results were negative. In one isolated instance two developmental forms were seen between the thoracic muscles of a Tœniorhynchus fuscopennatus reared from the larva and fed on infected persons. Fülleborn has found similar developmental forms once in An. maculipennis. Christy suggests that the true intermediary host of F. perstans is Ornithodoros moubata, a tick of the sub-family Argasinœ. He gives no evidence in support of this view, which is contradicted by the facts of geographical and topographical distribution.

Pathology.— So far as known, F. perstans has no great pathological importance ; the presence of the adult parasites in the mesentery appears to cause little harm to the host.

Microfilaria Demarquaii, Manson, 1895. (Plate X., Fig. 4.)

In examining blood sent me by Dr. Newsam from natives of St. Vincent, West Indies, I found this microfilaria in several individuals— in 10 out of 152 examined. It resembled mf. bancrofti and mf. loa so far as shape is concerned, but differed from them in size, its average measurements being, according to Low, 0.2 mm. by 0.005 mm. It is sharp-tailed, has no sheath, and observes no periodicity, being present in the peripheral circulation both by day and by night. Its movements are very active; it can shorten or elongate itself, and not only wriggle about very actively, but travel from place to place on the fresh blood slide. Nothing is known of its life-history or pathological bearings.

I have met with the same parasite in the blood of natives of St. Lucia, W.I. , an observation confirmed by Galgey, Low, and St. George Gray. Low has also found it in the blood of natives of Dominica and Trinidad. Usually some eight or ten parasites are found in a preparation of ordinary dimensions; occasionally instances of high degrees of infection are met with, in which hundreds of microfilariæ can be counted on every slide. Its topographical distribution is singularly circumscribed, even in the endemic districts.

Galgey found five adult female filariæ in the omental tissues of a patient in whose blood mf. demarquaii had been discovered during life. No male was found.

These worms closely resembled the adult F. ozzardi, but, according to Daniels, exhibited structural differences, especially as regards the shape of the head and tail, which led him to conclude that they are specifically distinct. They measured from 65-80 mm. in length by 0.21-0.25 mm. in breadth. The head has a diameter of from 0.09 to 0.1 mm. The mouth is terminal. The genital pore opens at 0.76 mm. from the head. The alimentary canal is nearly straight, and terminates in an anus which is subterminal. The opening of the anus is marked by a slight papilla. The tail is curved and rapidly diminishes in size just below the anal papilla. A marked cuticular thickening covers the tip of the tail. The diameter near the tip of the tail, before its termination, is 0.03 mm. F. demarquaii is a thicker worm than F. perstans. It differs from F. bancrofti and F. ozzardi in the greater size of the head, in the smaller tail, and particularly in the marked cuticular thickening at the tip of the tail. This thickening is knobby and bifid, but the divisions are not so well marked as in F. perstans. The intermediate host has not been discovered. Low believes it to be a rare species of mosquito. It is quite possible that some of the minute, sharp-tailed filariæ (F. ozzardi) of British Guiana are the same species.

I have also found a minute, non-sheathed, sharp-tailed microfilaria, closely resembling mf. demarquaii, in the blood of natives of New Guinea. Whether these various minute, sharp-tailed, non-sheathed embryos belong to one or to several species it is impossible to decide until the adult forms of each have been discovered and carefully compared.

Filaria Ozzardi, Manson, 1897

Some years ago I received from Dr. Ozzard, British Guiana, a number of blood films prepared from aboriginal Carib Indians inhabiting the back-country of that colony. Although the negroes and other inhabitants of the littoral and settled districts of British Guiana are very subject to F. bancrofti and to elephantiasis, in none of the considerable number of slides of Carib blood from time to time received from Drs. Ozzard and Daniels have I once encountered mf. bancrofti. Daniels records an identical experience. I am assured by Dr. Ozzard that elephantiasis is unknown amongst these people. On examining the blood slides referred to, I discovered certain nematode larvae with characters so peculiar that I suspected they represented at least one new species of blood worm, which I called, provisionally, F. ozzardi. At least half the slides examined contained these parasites, some slides only one or two, other slides as many as forty or fifty.

In size and shape five out of six of the embryos resembled very closely mf. perstans (p. 735)— that is to say, they were blunt-tailed, had no sheath, and were very minute (0.173 to 0.240 mm. by 0.0043 to 0.005 mm., Daniels). But along with the blunt-tailed filariæ, and on the same slides, there occurred a sharp-tailed form, also very minute, and resembling mf. demarquaii. Drs. Ozzard and Daniels confirmed this discovery. These observers found that both the sharp-tailed and the blunt- tailed worms behave in fresh blood on the microscope slide much in the same way that mf. perstans and mf. demarquaii do; that is, they wriggle about very actively, at the same time retracting, elongating, and locomoting in the blood.

Parental form.— For a time the relationship of these micro-filariæ, both to each other and to mf. demarquaii, remained undetermined. Later Daniels found parental filariæ— male and female— at the post-mortem examinations of two Demerara Indians whose blood, during life, contained both blunt- and sharp-tailed larvæ. The mature worms, apparently numerous, were about 3 in. in length and very slender— about one-half the diameter of F. bancrofti. They were, therefore, not F. magalhdesi (p. 741). The head was somewhat club-shaped and showed no papillae. The tail of the male was much coiled, and carried at least one long protruding spicule. These worms were found in one case in the mesentery and in the fat at the base of the mesentery; in the other " not only in mesentery and abdominal fat, but also in the subpericardial fat." The embryos in utero, Daniels stated, were all blunt-tailed. I had an opportunity of comparing these worms with unquestionable adult F. perstans. I found them to be identical. The peculiar bifid arrangement of the termination of the tail was quite characteristic of that parasite (p. 736).

Later, Daniels found at the post-mortem examination of a third aboriginal, in whose blood both the blunt-tailed (F. perstans) and the sharp-tailed microfilariæ had been found (and no others), a few adult F. peratans and, in addition, a female and portion of a male worm of quite a different species— presumably the parental form of the sharp-tailed larvae. The two latter adult worms lay close together, and were believed to have been located in the subperitoneal connective tissues in the anterior abdominal wall. Except in the matter of the caudal extremity, which was slightly bulbous and without

cuticular thickening, in size and structure they closely resembled F. bancrofti. Daniels has drawn up a table (p. 741) of the leading dimensions of the three species— F. bancrofti, F.perstans, and of this possibly new filaria for which I propose to retain provisionally the name F. ozzardi.*[10] (Fig. 128.)
Fig. 128.—A, Scheme for the measurement of certain fixed points of structure in microfilariæ, of value in the diagnosis of species. B shows that even in a shrunken specimen the measurements retain their same proportionate value. (After Fülleborn.)

Measurements: 1, From the ant. extremity to the nerve ring (N.); 2, to the middle of the excretory pore (Ex.P.); 3, to the nucleolus of the excretory cell (Ex.Z.); 4, to the nucleolus of the genital cell (G.1); 5, to the middle of the anal pore (A.P.); 6, to the terminal tail nucleus.

TABLE OF LEADING DIMENSIONS OF FILARIÆ

  Filaria
bancrofti
Filaria perstans Filaria
ozzardi
  Mm. Mm. Mm.
Length 85 to 90 70 to 80 81
Greatest thickness 0·20 to 0·26 0·120 0·210
Diameter of head 0·055 0·070 0·050
Diameter of neck 0·049 0·054 0·039
Distance from head—      
(1) Of vaginal outlet 0·710 0·600 0·710
(2) Of ovarian opening 0·920 ? 0·850
Distance from tail of anal papilla 0·225 0·145 0·230
Termination of tail Blunt, circular,
not bulbous.
Slightly bulbous;
covered by thickened
cuticle prolonged
into two
triangular appendages.
Bulbous
cuticle not
thickened.

Filaria magalhãesi, R. Blanch., 1895

Professor Magalhăes describes two sexually mature filarial hæmatozoa, male and female, which were found lying in the left ventricle of the heart of a child in Rio de Janeiro. No information was received as to the nature of the disease of which the child died, nor had any examination of the blood been made during life. The parasites were cylindrical, capillary, opalescent, white, uniform in thickness except, where the body tapered towards the tail and at the club-shaped oral end. The mouth was simple, circular, unarmed; the cuticle marked with fine transverse striations. The female worm measured 155 mm. in length by 0·7 mm. in diameter, the male 83 mm. in length by 0·4 mm. in diameter. The tail of the latter was provided with four pairs of preanal and four pairs of postanal papillæ, and two spicules. Manifestly this parasite is specifically distinct from F. bancrofti and the other blood worms described above. Nothing is known of its life-history, nor of the associated pathology.

  1. * The term microfilaria has been suggested by Le Dantec to designate the larval forms of the various nematodes whose young circulate in the blood. I adopt it as being a convenient expression.
  2. Rodenwaldt's method of vital staining with neutral red and azur II. is serviceable for demonstrating finer points of structure and morphological differences between different species. A large drop of blood is covered with a cover-slip and allowed to stand till the red blood-corpuscles have separated into rouleaux. A piece of thick blotting-paper is placed at the edge, and a dilute solution of the stain in 9-per-cent. normal saline allowed to flow through. By these means the blood corpuscles are removed and the micro-filariæ adhere to the cover-glass, becoming stained while still alive or freshly dead.
  3. * I have had an opportunity of examining the day and night blood of a filariated native of Northern Nigeria. In this case the periodicity was definitely noeturnal.
  4. Several species of mosquitoes may subserve F. bancrofti, viz.: Culex fatigana, Mansonia uniformis and titillans, Anopheles maculipennis, Myzomyia rossii, Myzorhynchus nigerrimus, minutus, and funestus, Pyretophorus costalis, Cellia argyrotarsis, Stegomyia pseudoscutellaris (Stegomyia fasciata probably occasionally). Culex fatigans is the first in which it was found.
  5. This casting of its sheath by the microfilaria can be induced in ordinary blood slides by chilling them on ice, or by otherwise bringing about the diffusion of the hæmoglobin. The following method is usually successful: Ring with vaseline the cover-glasses of several ordinary wet preparations of finger blood obtained at night from a filarial patient; wrap the preparations separately in filter paper and lay them, enclosed in a watertight tin box, on a block of ice for six or eight hours—say overnight. Next morning examine them with the microscope. It will be found, as the chilled slides warm up, that wherever on the slides the hæmoglobin has become diffused and the blood laky, the microfilariæ, as they gradually revive from the chilling, begin to endeavour to break through their sheaths. By evening most of them have effected this, and their empty sheaths can be seen lying scattered about in the viscid blood. The blood must not be frozen.
  6. Annett and Dutton pointed out that there is a weak point in the chitinous skeleton of the labium just where the labella are jointed on, and suggested that it is at this weak point the parasites escape. Bancroft confirmed this suggestion by showing that the filariæ enclosed within the labium will escape readily at this point under the least pressure. Noè also, in a more recent paper, agrees with Annett and Dutton and rejects his former hypothesis (held in common with Grassi) to the effect that the filariæ escape through a rupture in the contiguity of the labium when it is buckled up during haustellation. Noè satisfied himself by numerous experiments that the filariæ invariably die when extruded at the seat of the bend. Finally, Lebredo, by actual experiment, proved that the filariæ escape in this way. He placed living mosquitoes on slides, irrigated them with a weak saline solution, and placed them on the stage of the microscope. He separated the various parts of the proboscis by a slight pressure so as to observe more clearly, and placed the flame of a Bunsen burner close to the slide. He noticed that the filariæ moved violently within the labium when the liquid in which the mosquito was bathed attained a higher temperature. Finally, one managed to pierce its way through at the tip of the labium, and was soon followed by others. He noticed the escape of five filariæ within a minute. Sometimes two passed simultaneously. Too high a temperature killed both larvæ and mosquito. A fall of temperature arrested the process.
  7. * In my original observations on this subject in 1879 and 1883 (Trans. Linnean Soc., 1883) I supposed that filarial metamorphosis, so far as the mosquito was concerned, is completed in from six to seven days. This I now believe was too short an estimate. Bancroft (Journ. of Trop. Med., 1899) has since shown that it is necessary to feed the experimental mosquito (at all events, C. fatigans), so as to keep it alive for at least sixteen days, to obtain the final stages of the metamorphosis. (Fig. 106. ) I have little doubt now that the insects on which my observations were made had fed repeatedly, without my being aware of it, after their meal on the filariated patient. Bancroft has shown that by proper feeding (he used banana for the purpose) mosquitoes may be kept alive for several months, any filariæ they happen to harbour remaining alive, but not advancing in development beyond the final stage alluded to in the above description. In the observations referred to I conjectured that the fully metamorphosed filaria escaped from the insect either at her death or when she deposited her eggs, and that thus, in drinking-water, it obtained a chance of gaining access to the stomach of a human host. Before Low's observation Bancroft had very nearly guessed the truth, for he had expressed the idea that the filaria may be injected into man by the mosquito when it re-feeds, or that it may be swallowed by man while it is still enclosed in its intermediary insect host.
  8. * Wise and Minett, during the last few years, have found filariæ living, or cretified, in the following situations, viz. pelvis of kidney (31 times), epididymis (18 times), retroperitoneum (12 times), the ilio-psoas muscle (4 times), Glisson's capsule (twice), inguinal glands (25 times), lymphatic vessels (8 times). Similar observations have been made by Bahr in Fiji.
  9. * The sanguineous appearance so frequently seen in chylous urine and in other forms of filarial lymphorrhagia probably depends in some instances on the formation of blood-corpuscles in lymph long retained in the varicose vessels, and as a result of the normal evolution of the formed elements in that fluid in other instances it is probably caused by rupture of small blood-vessels into the dilated lymphatics.
  10. * It now seems probable that there is but one species, F. demarquaii. In this event the other name, in conformity with the rules of nomenclature, would ha.ve to be dropped; but as the name F. demarquaii has already been used erroneously for micro-tilaria bancrofti, it cannot be retained for a different parasite. The name F. ozzardi therefore succeeds to F. demarquaii. Leiper affirms that the recorded adults of F. ozzardi (as distinguished from those of F. demarquaii) are undoubtedly specimens of F.bancrofti.