make it clear how a worm l.iO M in diameter is able to pass 

 througli capillaries, or why the worms appear iu the ab- 

 dominal aorta before the thoracic, and never cause lesions 

 in vessels anterior to the aortic arch. It seems far more likely 

 that the larvae follow^ the route indicated by Hu and Hoeppli 

 (1936) ; after penetrating the gastric wall they proceed to the 

 coronary, gastroepiploic and coeliac arteries, and via these 

 to the upper abdominal and lower thoracic portions of the 

 aorta, eventually reaching the upjier thoracic aorta from below. 

 In the aorta the worms attach themselves to the wall and 

 cause the formation of characteristic nodules. Some worms 

 remain iu this position but many migrate outward through 

 the aortic wall and through the intervening tissue until they 

 reach the esophageal wall, iii which they find a favorable habi- 

 tat in which to reach maturity and reproduce. The eggs reach 

 the lumen of the esophagus through a secondary opening 

 from the tumor in its wall. 



FILARIOIDEA 



The Filarioidea are unique among nematodes, so far as is 

 known at present, in having perfected a mechanism by which 

 bott exit from and entrance to a host takes place through the 

 skin. The larvae of Dracuueuloidea escape through the skin, 

 though by a different mechanism, and the habronemas suc- 

 ceed in infecting a host when deposited on certain areas 

 of skin (the lips) but in neither case is both exit and entrance 

 accomplished by way of the skin. As noted under the discus- 

 sion of Spiruroidea, the evolutionary process by which the life 

 cycle of iilariae developed is clearly foreshadowed by the 

 course of events in the case of Eabronema. 



WUCHEMailA BANCBOFTI 



Hanson's (1878) discovery of the ingestion of filarial em- 

 bryos by mosquitoes and their development in these insects set 

 a landmark in the history of medical entomology, since it was 

 the first instance of a human blood infection being transmit- 

 ted by an insect. Low (1900) first demonstrated the mechanism 

 by which the larvae were returned from mosquitoes to man, 

 and Annett, Dutton and Elliott (1901), Lebredo (1905), 

 and Bahr (1912) added further details. 



The adult worms live iu the lymphatic system and liberate 

 their larvae, known as microfilariae, into this system, whence 

 they eventually, unless blocked, make their way into the blood 

 stream. Their presence in the peripheral blood is periodic in 

 most parts of the world, being present at night, but not in 

 the daytime. Similar periodicity, though often less complete, 

 is observed in many other filarial infections; in some spe- 

 cies, however, e.g., Loa loa, there is a diurnal periodicity, and 

 in others, e.g., Dipetaloncma perstans, no periodicity has been 

 observed. Two principal theories have been proposed to ac- 

 count for the periodicity: one, originally advanced by Man 

 son, is that the larvae retire to internal organs during the 

 day and enter the peripheral circulation only at night ; the 

 other, advanced by Lane (1929), is that the worms have cycli- 

 cal parturition, producing their entire day's output of larvae 

 at the same time each day, and that these worms are all 

 destroyed in the host within 12 hours after they appear in 

 the blood stream. Some support is given to this theory by 

 O'Connor's (1931) observation at autopsies that at certain 

 hours all the adult female filariae have their uteri crowded 

 with embryos, while at other hours they are uniformly spent. 

 On the other hand, the persistence for a year or more of mi- 

 crofilariae transferred to an uninfected host (Underwood and 

 Harwood, 1939) is against this theory, though the fate of 

 microfilariae in infected and nou-iufected hosts may not be at 

 all comparable. As yet there is no unanimity of opinion as 

 to the reason for microfilarial periodicity. 



The microfilariae of Wuchereria bancrofti as seen iu blood 

 smears are covered by a sheath which has very generally been 

 thought to be not a shed cuticle but a delicate, stretched vitel- 

 line membrane. Augustine (1937) questioned this, since he 

 observed that developing microfilariae in the uterus of Vagri- 

 filaria columbigallinae clearly show the vitelline membrane sur- 

 rounding eggs containing coiled larvae, but none of the micro- 

 filariae from the vaginal region show any evidence of a sheath, 

 and accumulations of crumpled hyaliue ob.iccts interpreted as 

 the remains of discarded vitelline membranes were found at a 

 higher level in the uterus, .lugustine was able to see no evi- 

 dence of a sheath on the microfilariae of this species while they 

 were in capillaries but was able to follow its formation on dry- 

 ing slides. He concludes, therefore, that the sheath is, as in 

 other sheathed nematode larvae, the loosened but unshed cuti- 

 cle from an incomplete ecdysis. This conclusion seems to us, 

 however, to be very doubtful, since no other nematode larvae 

 are known to molt at such an early stage in development, and 



since two other molts have been observed during the course of 

 development of the larvae in their mosquito hosts; this would 

 bring them to the third stage, which is usual for infective lar- 

 vae in intermediate hosts (see p. 237). Some species of 

 filariae are not provided with sheaths. 



The larvae are in a very immature state of development. 

 They are covered by a layer of sub cuticular cells, and within 

 the body have a column of nuclei which subsequently develop 

 into the esophagus and intestine. 



This column of cells is broken at certain definite spots rep- 

 resenting the future position of the nerve ring, the excretory 

 pore and cell, and the anus. There are also a few large cells: 

 an excretory cell just posterior to the excretory pore, a genital 

 cell well behind the middle of the body, and a group of three 

 cells previously reported as genital cells 2 to 4, but which 

 Feng (1936) says give rise to the anus and rectum, and which 

 Abe (1937) says belong to the sphincter between intestine and 

 rectum, and are ultimately lost. There is a difference of opin- 

 ion as to the existence of a stylet at the anterior end of the 

 worm. The structure so called appears to be a rudimentary 

 mouth cavity. 



Upon ingestion by suitable species of mosquitoes the larvae 

 become unsheathed iu the stomach and penetrate into the body 

 cavity, whence the majority migrate at once to the thoracic 

 muscles, where development to the infective stage takes place. 

 The factors which determine the suitability of particular mos- 

 quitoes have not been elucidated. Development takes place 

 readily in mosquitoes of a variety of genera, including Ano- 

 pheles, Culex and Aedes, but sometimes nearly related species 

 within these genera differ widely in their ability to serve as 

 nurses. For example, Culex quitiquefasciatus and C. pipiens 

 are good hosts, whereas C. vexans is not ; and Aedes variegatns 

 is a very good host whereas A. aepi/pti and A. albopictus are 

 not. As yet nobody has succeeded in obtaining development 

 in any arthropods other than mosquitoes. 



Upon arrival in the thoracic muscles the larvae become qui- 

 escent, lying parallel with the muscle cells. Here in the course 

 of 2 or 3 days they become considerably foreshortened, often to 

 approximately half their original length, and at the same 

 time grow considerably in girth, assuming what is known as 

 the "sausage" stage. Only the caudal tip of the body fails to 

 thicken, and is retained as an attenuated tail-like structure. 

 Meanwhile a large excretory bladder develops and subsequently 

 a large rectal cavity, and the outlines of the esophagus and 

 intestine become defined. On the fifth day, according to Abe 

 (1937), the larva undergoes its first molt, the cuticle develop- 

 ing an annular break near the anterior end. After this molt 

 the larva reaches its maximum shortness and thickness and then, 

 as the alimentary canal becomes well developed, begins to 

 lengthen. As it approaches its maximum length it becomes 

 active again and, according to Abe (I.e.), undergoes a second 

 molt about the time it is ready to leave the thoracic muscles 

 (In his experiments on the 13th day). The loosened cuticle 

 breaks near the middle of the body and is shed. The larvae 

 now become active and migrate out of the thorax. The ma- 

 jority go through the neck and head and move down into the 

 interior of the labium, but a few get lost and can be fouud in 

 the abdomen, legs, palpi, etc. Infective larvae commonly reach 

 the labium about 2 weeks after infection in warm weather, but 

 have been known to complete their development in 9% days. 

 In the labium they are stimulated by warmth, and when the 

 mosquito is biting, escape through the delicate membrane where 

 the labella join the shaft of the labium. The larvae do not, 

 of course, interfere with skin-piercing as do the larvae of 

 Habroncma in the labium of Stomoxys, since in mosquitoes 

 the labium itself is not a piercing or sucking organ. After 

 leaving the proboscis and becoming free on the skin the larvae 

 were believed by Fiilleborn (1908), on the basis of experiments 

 with Dirofilaria imniitis, to penetrate into pores and enter 

 through unbroken skin, but Yokogawa (1938) carried out a 

 series of experiments which indicate that they can only enter 

 broken skin, and presumably in nature use the wound made 

 by the mosquito. 



Nothing is known about the development of the larvae after 

 they enter a human host until they reach maturity iu the lym- 

 phatic system. Dirofilaria immitis requires about 9 months to 

 reach maturity, and it is improbable that IViichrrcria bancrofti 

 takes any longer, if as long. 



Other Fll.iriae 



The life cycles of comparatively few species of filariae are 

 known, but among those that are known there is comparatively 

 little variation. As already noted, some microfilariae are 

 sheathed and some are not, but there is no evidence that the 

 presence of a sheath has a "muzzling" effect in keeping the 

 microfilariae from passing in or out of the capillaries, as Man- 

 son had thought. This was shown by O'Connor (1931) in the 



288 



