[gammon BLOOD AND TISSUE PARASITES of Man / Life Cycle Charts --—..,“_ > ; . S U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE PUBLIC HEALTH SERVICE tCENTER FOR DISEASE CONTROL :- Common dBLOOD AND TISSUE PARASITES/‘j of Man Life Cycle Charts PREPARED BY D. M. Melvin, M. M. Brooke, G. R. Healy and K. W. Walls Bureau of Laboratories Laboratory Training and Consultation Division and Parasitology Division U. S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE PUBLIC HEALTH SERVICE Center for Disease Control Atlanta, Georgia 30333 a; (v DH EW EMMACDC) 80-8383 ‘ é‘iéS 9694f ,DMEZ. These charts were originally issued in 1961 as an unnumbered publication by the Laboratory Branch of the Center for Disease Control for use m training courses. Q /2% /%fl( Revised 1979 Reprinted 1980 ]____,_ I! R c T 119 C33 , 1979 I. Introduction .......................................... I PUBL CONTENTS L.__._,A #3.. _vu. i)u.__._..l [1. Blood Parasites ........................................ 3”" '7' '4 " Malaria ........................ l .................. 3 Babcsia ........................................... (» Hemoflagellales ...................................... IO [,c’islmzam'a ....................................... IO Trypanosomes .................................... I I FiIaria ............................................ I7 Dracullcu/us ........................................ 37 HI. TissueParasites.......i...................H....‘...i,.2‘) Helminths ........ 3‘) Tric/Iinella spiralis .................................. :0 Larva Migrans ...................................... i 0 ‘lfc'llillucnccus ..................................... 2 Pmtozoa ......................................... 3 3 Tnxoplasma gain/[1' .................................. 1 3 Free-living Amebae .................................. 3 3 Figures Life Cycle Charts Malaria ............................................. x Babosia ............................................. 0 lmislmzania ........................................... 14 Trvpanosnnza bruccigambiense and T. brucci rhodcsiense ............ I 5 levpannsoma ('rZIZi ..................................... 16 lt’m/zcrcriu bum-mfti .................................... 30 Brugia maluvl'i ........................................ 31 /.ua [0a ............................................. 23 l/IIa/Isonvlla uzzanli ..................................... 33 Dipcmluncnw persraus ................................... 24 Dipc/almmna slrvptnvcrca ................................ 25 ()nc/mc'crcu mll'ulus .................................... 26 Dracum'u/us mediumsis .................................. 28 Trichincl/a splra/is ...................................... 35 Toxnc'ara canis ........................................ 36 [ft/limu'nc'cusgrunu/osus .................................. 37 Toxop/usma gmnliz‘ ..................................... 38 NaL'g/cria fim'lc’ri ...................................... 39 203366 iii Tables 1. Average Development Times for Malaria ....................... 4 ll. Characteristics of Filariae ................................. 19 I. INTRODUCTION The blood and tissue parasites of man include representatives of two groups of helminths, nematodes and cestodes, and of three groups of pro- tozoa, hemoflagellates, sporozoa, and amebae. In general, the life cycles of these parasites tend to be more complex than those of the intestinal para- sites and, in the case of blood parasites, involve an arthropod vector as well as a human host. Intermediate hosts are necessary for the transmis- sion of most of the blood and tissue organisms and, in several cases, reser- voir hosts are important. With the exception of Toxoplasma gondii and Togcoc'ara cams, no external development takes place. Naegleria and related genera of amebae, however, are actually free-living rather than parasitic organisms, and their normal life cycle takes place entirely in the environment. Like the life cycle charts of the intestinal parasites,* the life cycle charts of the blood and tissue parasites are intended for use by students of parasitology. laboratory personnel, public health workers, and physicians. They are simple, basic charts that purposely omit details of epidemiology, incubation periods, prepatent and patent periods, and exceptions to the usual pattern. The individual user can add any needed or desired details obtained from lectures orfrom the scientific literature. Pneumocystis carinii has been excluded from this presentation, since neither the correct classification nor the complete life history has been determined. The design of the charts conforms to the following general rules, inso- far as possible: 1. The diagnostic and infective stages are indicated and emphasized. The sizes of these stages are in proportion with regard to species within a given group but, because of size variations, the scale is not uniform between groups. The sizes of the nematode male and female adults are relative to each other and, within the filariae, are drawn to a single scale. *Melvin, D.M., Brooke, MM. and Sadun, EH. 1965: Common Intestinal Helminths of Man rrLife Cycle Charts. DHEW Publication No. (Center for Disease Control) 75-8286 (Formerly Public Health Service Publication No. 1235). Atlanta, Georgia. Brooke, MM. and Melvin, BM. 1964: Common Intestinal Protozoa of Man—Life Cycle Charts. Public Health Service Publication No. 1140. Center for Disease Control, Atlanta, Georgia. 2, Morphologic details are included in a diagrammatic fashion in most of the stages of the protozoa, but only in the diagnostic and infective stages ofthe helminths. 3. Survival times, prepatent and patent periods, and developmental times are omitted. 4. Not all of the embryonic and larval stages of the helminths are in- dicated. For example, the number of nematode larval stages is not recorded. 5. Only broad groups of organisms are indicated as invertebrate intermediate hosts. More specific names are applied to mammalian hosts. (3. Reservoir hosts are not listed on the charts but in cases where man is an accidental or abnormal host, the common hosts are indicated. 7. No general references are listed, since the material incorporated into the chartsis commonly found in most parasitology textbooks. Where necessary, however, specific references have been included. In this revised edition, the original charts have been updated and four new ones, Tuxoplasma, Babesia, Naegleria, and Dipetalonema streptocerca, have been added. [‘J II. BLOOD PARASITES The blood parasites presented here include malaria, Babesia, hemo- flagellates, and filaria. Not all of the species of each group actually inhabit the blood stream (for example, adult filaria, Leishmania spp.) but most are associated with the circulatory system at some stage of their develop- ment. The leishmania probably should be considered as tissue rather than blood parasites, but since they are classified as hemoflagellates, they are presented here with the blood—inhabiting forms. Another tissue parasite, Dracunculus medinensz’s is usually put in the same general category as the filariae; it too is included with the blood parasites in these charts. MALARIA The life history of malaria is similar to that of the intestinal sporozoa. the coccidia, and involves an asexual cycle, schizogony, in the human host and a sexual cycle, sporogony, in the vector, a species of Anopheles mosquito. The pattern presented here is that of Plasmodium l’il’ax but, in general, it is the same for all four species. Immediately after the introduction of the infective sporozoites through the bite of the mosquito, a preerythrocytic (exoerythrocytic) development occurs. In man, these exoerythrocytic stages have been demonstrated in the parenchymal cells of the liver. The number of days before parasites can be demonstrated in blood films (the prepatent period) indicates that this preerythrocytic development probably requires a week or more, depending on the species involved (Table I). For many years, the exoerythrocytic development in the liver was considered cyclic, with recurring asexual generations. More recent evi- dence suggests that this phase is not cyclic and that only one generation occurs before merozoites are released into the circulation (Contacos and Collins, 1973; Coatney et al., 1971). In P. vivax and Plasmodium ovale, there is evidence that some of the exoerythrocytic forms are delayed in completing their maturation, and in these two infections, exoerythrocytic forms may persist in the liver cells during and after the initial erythrocytic phase. In Plasmodium falciparum and Plasmodium malariae, on the other hand, residual exoerythrocytic stages probably do not occur, since neither of these have true relapse activity. The pres- ence or absence of residual exoerythrocytic stages affects both the clinical course and the therapy of the disease. The residual forms are associated with relapses of P. vivax and P. ovale TABLE I AVERAGE DEVELOPMENT TIMES OF MALAR|A* Length of Preerythrocytic Phase P. vivax P. ova/e P. malariae P. fa/ciparum Approx. 8 days Approx. 9 days Approx. 12 days Approx. 6—7 days Length of Prepatent Period 11-13 days 14—15 days 15-16 days 9-13 days Length of Erythrocytic Asexual Cycle 42—48 hours 48-50 hours 72 hours 48 hours Length of Sexual Cycle in Mosquito 8—1 2 days 14-15 days 15-21 days 12-14 days (Optimum conditions) *Boyd, M. F., 1949: Malariology. W. B. Saunders Co., Philadelphia. Coatney, G.R., Collins, W.E., Warren, McW., and Contacos, P.G., 1971: The Primate Malarias, National Institutes of Health, Bethesda, Maryland. Garnham, P.C.C., 1966: Malaria Parasites and Other Haemosporidia. Blackwell Scientific Publications, Oxford. The asexual stages of malaria include trophozoites and schizonts and, except in P. falciparum, all stages of growth may be found in peripheral blood. P. falciparum organisms complete their schizogony in the capil- laries of the internal organs so that usually only the rings (young tropho— zoites) of the asexual forms are seen in the circulating blood. In addition to the asexual stages, gametocytes (sexual forms) develop in man and in all four species may be found in peripheral blood. Their exact origin is unknown, but they probably develop from certain of the merozoites produced in the erythrocytic schi onts. Gametocytes are the infective stages for the mosquito and, in the arthropod stomach, develop into gametes which initiate the sexual cycle. They do not multiply in the human host, and unless ingested by the appropriate mosquito, will degen- erate and eventually die. The sexual development, ending in production of sporozoites, the infective stage for man, is influenced by such extrinsic factors as temperature and humidity. The average lengths of both sexual and asexual cycles for each species are included in Table I. These are based on reports in the scientific literature (by various investigators) and rep- resent the more common average development periods as recorded. Only female Anopheles are involved as hosts for human malaria. Over 60 species, from different areas of the world, are considered vectors of malaria. In the United States, two are considered to be important vectors: A. quadrimaculatus in the east and A. freeborni in the west. Not all species of Anopheles serve as malaria vectors, either because they are not good biological hosts or because they normally do not feed on human blood. Malaria infections can be spread from man to man via blood inocula- tions, for example, through transfused blood or hypodermic needles used in common by drug addicts. In these cases, an exoerythrocytic phase does not occur. Exoerythrocytic development takes place only after sporozoite inoculation. Man is generally considered to be the natural vertebrate host for the four species of human malaria. However, it has been experimentally demonstrated that several malaria species parasitic in nonhuman primates (monkeys, chimpanzees, and others) can be transmitted to man through mosquito bites. Except for one human infection with Plasmodium knowl— esi (Chin et al., 1965), natural transmission of simian malaria to man has not been definitely established. Nevertheless, the possibility of monkey- to-man infection exists. BABES/A Babesia organisms are intraerythrocytic parasites of a wide variety of wild and domestic animals, including dogs, cattle, horses, and rodents. In 1957 a human infection with B. bovis, a cattle species, was reported from man. This first case and other earlier ones reported occurred in persons who had been splenectomized for various reasons. It was assumed, there- fore, that only humans who had undergone splenectomy were susceptible to infection with this organism. In the past several years, a number of cases have been reported in the northeastern United States in nonsplenec- tomized persons, thus disproving the earlier assumption (Ruebush et (11., 1977). The parasite stages seen in the blood, particularly in B. microti, a rodent form, resemble those of malaria, especially Plasmodium falcipa- rum, and the infection may thus be misdiagnosed as malaria. It is there- fore probable that Babesia occurs more commonly in humans than reports indicate. Babesia species are transmitted by several genera of hard ticks, includ- ing Boophilus, Ixodes, Dermacentor, and Rhipz'cephalus. Different species of Babesia utilize different vector species to complete their life cycle. The exact pattern of development in the tick probably varies slightly with the species of Babesia (Ristic and Lewis, 1977). Not all developmental stages in the tick vector have been worked out. An important aspect of the transmission, however, is the fact that Babesia can be transmitted trans- ovarially from adult female ticks to offspring. The Babesia parasites in the vertebrate red blood cells are ingested by either the male or female tick during its blood meal. The organism is phagocytized by cells of the intestinal epithelium and undergoes multiplication by binary fission in a type of schizogony. The infected epithelial cell eventually ruptures, and organisms called vermicules penetrate other intestinal cells, hemocytes, Malpighian tubules, or ovaries in their spread through the tick hemolymph to other tissues. Parasites which penetrate the ovary are eventually incorp— orated into the developing eggs and are subsequently found in the larval tick which may transmit the infection to the vertebrate host. The organ- isms may persist, multiply, and enter the salivary glands of the nymph at which stage they may persist through the nymphal stage. Finally, when the nymph molts, the adult tick can transmit the infection. (Different species of Babesia have different cycles in this regard.) The parasites transmitted by the tick are called “pyriform bodies” and are the infective stages for the vertebrate host. They gain access to the definitive host through the bite of the tick. As stated, both male and female ticks bite, but only the female is important in the perpetuation of Babesia in the absence of infective hosts for a long period of time. In the vertebrate host, the pyriform bodies enter the red cells and divide by binary fission. These erythrocytic forms, or trophozoites, may be pyriform, oval, or round, and are often ameboid. Morphologically, they resemble ring forms of malaria and, in man, may easily be confused with them. As in malaria infections, a red cell may contain several para- sites. In some species, tetrads are formed as a result of fission; in others, only two organisms or merozoites, are produced. No gametocytes are found in Babesia infections. Neither do the organisms contain hemozoin pigment as do malaria parasites nor is there enlargement or other altera- tion of the infected red blood cell morphology. Several species, particularly B. microti, a rodent species, have been tentatively identified as etiologic agents of human babesiosis. This species caused the cases reported from the northeastern part of the United States. The life cycles of the various Babesia species differ slightly in minor points, and the cycle depicted here is intended to be more or less typical, but general rather than specific. The development in the tick is based on that described for B. bigemz’na; the development in the vertebrate is based on that described for B. microti. REFERENCES CITED Chin, W., Contacos, P.G., Coatney, G.R., and Kimball, H. 1965. A naturally acquired quotidian-type malaria in man transferable to monkeys. Science 149 (3686):815. Coatney, G.R., Collins, W.E., Warren, McW., and Contacos, RC. 1971. The Primate Malarias. National Institutes of Health, Bethesda, Maryland Contacos, PG. and Collins, W.E. 1973 Malaria relapse mechanism. Trans. Roy. Soc. Trop. Med. and Hyg. 67(4): 617-618. Ristic, M. and Lewis, G.E., Jr. 1977 Babesia in man and wild and laboratory - adapted mammals. Chapter 2 in Parasitic Protozoa, J .P. Kreier, ed. Academic Press, New York Ruebush, T.K., Cassaday, P.B., Marsh, H.J., Lisker, S.A., Voorkees, D.B., Mahoney, E.B., and Healy, G.R., 1977 Human babesiosis on Nantucket Island: Clinical Features. Ann. Intern. Med. 86 (l):6-9. llFE CYCLE of— . Spomonu m uumy gum- ‘ (infective nun) MOSQUITO 06¢:le mpmm la libumd Band on Me cycle afPlumodtwn viva! UFE CYCLE of— Babesia 00/ Tglfld O 0 Memzoiles ERYTHROCYTIC CYCLE Trophozoile RODENTS, HORSES, Pencil-imam!“ CATTLE, DOGS, MAN, NJ“, AND OTHER VERTEBRATES‘ lick during hi1: (dugnosnc sage) 00g Pyrifonn bodiel (infective mp) Stliury fllndl (ldull. nymph. lam) lngested G Trophuluile v HARD TICKS" Phagocytosed by gm cell Tnnwurial mmm‘ml\nn I ‘x W\ M. R:\produm' In hemocym Malpighlnn tubules, muscle cells VVe\nnicule v” ) Tnnsfonns inlu vumicules \‘7...~ Cell 4’ mplurex ‘Bued on E. mit'roll‘ " Based on B. Dunning HEMOFLAGELLATES The life history patterns of the hemoflagellates, like the pattern of malaria, involve an arthropod vector which is chiefly responsible for the transmission and spread of the infection. The vectors for the hemo- flagellates are various species of insects, and the specificity of the vector usually limits the geographical distribution of the parasite. Unlike most of the other blood parasites, the hemoflagellates do not possess sexual forms, and they multiply entirely through binary fission in one or more of the morphologic stages. Species of two genera, Trypano— soma and Leishmanz‘a, parasitize man. Four morphologic stages are de- scribed (Hoare and Wallace, 1966): 1) amastigote, a rounded nonflagel— lated form possessing a nucleus and rod-like kinetoplast; 2) promastigote, an elongate flagellated form with an anteriorly located kinetoplast, but no undulating membrane; 3) epimastigote, an elongated flagellated form with a short undulating membrane and the kinetoplast located just anterior to the nucleus; and 4) trypomastigote, an elongated flagellated form with a fully developed undulating membrane extending the length of the body and a posteriorly located kinetoplast. Leishmania In the human host, Leishmania spp. exist only in the amastigote form and are intracellular parasites of reticulo—endothelial cells. The species affecting man are Leishmania donovani (visceral leishmaniasis), Leish- mania tropica, Leishmania brasiliensis, and Leishmania mexicana (cutan- eous leishmaniasis). Each of these probably represents a complex of several species and subspecies of Leishmania; however, there is some doubt that all of these are valid species. Since the morphologic stages and life cycles of all of these species are more or less identical, they are pre- sented in a single chart. In the arthropod vectors, which are certain species of Phlebotomus and Lutzomyia (sand flies), the amastigote stages taken up during the insect bite transform into the promastigote forms. These promastigotes divide in the midgut and in 3 to 5 days move to the proboscis of the sand fly. When the insect feeds again, the promastigotes (infective forms) are injected into the vertebrate host where they again become amastigotes Within reticulo-endothelial cells. Several species of Phlebotomus have been incriminated as vectors of leishmania in the eastern hemisphere (Asia, Africa, and Europe), among them P. argentipes and P. martini for L. donovani, and P. papatasz' and P. 10 sergenti for L. tropica. In the Americas, several species of Lutzomyia are involved, including L. longipalpis for visceral leishmaniasis and L. parensis, L. olmeca, and L. anduzei for cutaneous leishmaniasis (Bray, 1974). Only the female sand flies transmit leishmania organisms. Dogs, rodents, and possibly other mammals may serve as reservoir hosts. Trypanosomes Four species of trypanosomes are known to infect man: T rypanosoma brucei gambiense and Trypanosoma brucei rhodesz‘ense, etiologic agents of African sleeping sickness (African trypanosomiasis), Trypanosoma cruzi, etiologic agent of Chagas’ Disease (American trypanosomiasis) and Try- panosoma rangeli, a non-pathogenic species found in South and Central America. Since the development of T. rangeli in the mammalian host is not completely known (Hoare, 1972), this species has not been included in the charts presented here. The two African trypanosomes are considered to be subspecies of Trypanosoma brucei and are designated as Trypanosoma brucei gambicnse and Trypanosoma brucei rhodesiense. They are morphologically identical; furthermore, the life cycles are similar and are shown in a single chart. These species occur in man only in the trypomastigote form and are ordinarily located in the bloodstream and lymph nodes in the early phases of infection and in the central nervous system (primarily T. b. gambiense) in the chronic phases. They multiply in man by longitudinal binary fission of the trypomastigotes. In the arthropod vector (a species of tsetse fly) the trypomastigotes, taken up during the bite, multiply by binary fission in this stage in the midgut. They then migrate to the salivary glands, where they become epimastigote forms and undergo a second multiplication. In about 2 to 3 weeks they become metacyclic trypomastigotes. These infective-stage trypomastigotes are introduced into the vertebrate host when the fly bites again. Both male and female tsetse flies transmit the parasites. After entering the vertebrate host, the organisms initially lodge in the tissues around the bite wound, where they undergo division. In a few days, they enter the blood and, shortly after, the lymphatics. The try- pomastigotes divide repeatedly in both blood and the lymph system in the early stages of the infection. In the later stages, the organisms invade the central nervous system and are present in cerebrospinal fluid. The principal species of tsetse flies which serve as vectors for the two trypanosome species are Glossina palpalis, G. fuscipes, and G. tacki- ll noides for T.b. gambiense and G. morsitans, G. pallidipes and G. swyn- nertom‘ for T.b. rhodesiense. The choice of specific vectors determines to a degree the geographical distribution of the trypanosome infections: T.b. gambiense is found chiefly in tropical West and Central Africa and T.b. rhodesiense in East Africa. Overlapping of the trypanosome species, however, occurs in some areas. Certain wild mammals, primarily species of antelope, probably are reservoir hosts for T.b. rhodesiense, and cattle, hogs, and goats may possibly serve as reservoir hosts for T.b. gambiense. The life cycle of T. cruzi is markedly different from that of the African trypanosomes. In the mammalian host, two forms, the trypo- mastigote and the amastigote, are found. The trypomastigote form is usually found in the bloodstream during the early acute phase and during febrile periods. The amastigote stage is found in the tissue, usually in either reticulo-endothelial cells or heart muscle cells. Occasionally, it is found within macrophages in the blood. In the vertebrate host, the parasite divides only in the amastigote stage. The vector, a species of triatomid bug, may ingest the trypomastigote stage in blood or the amastigote stage in a macrophage during feeding. In the bug foregut, the trypomastigotes transform into rounded amastigotes. (Some workers have described flagellated round forms, which they call sphaeromastigotes.) The organisms divide repeatedly by binary fission, then move into the midgut region. There they gradually become epimasti- gotes and further multiply. The epimastigotes move to the hind gut and eventually transform into metacyclic trypomastigotes, which are the infective stage. Several intermediate developing stages (for example, sphaeromastigotes) have been described at various stages of the cycle in the bug, but for the sake of simplicity, they have been omitted from the chart. Both male and female bugs transmit T. cruzi. The infective metacyclic trypomastigotes are passed in the feces discharged as the bug feeds and ordinarily enter the mammalian host by being rubbed into the bite wound. Within the vertebrate host, the try- pomastigotes soon penetrate into tissue cells, or are engulfed by macro— phages, and transform into amastigotes. In the cells the amastigotes divide by binary fission, evolve into epimastigotes and further divide. Eventually, they become trypomastigotes, which are released into the bloodstream when the cell ruptures. The trypomastigotes circulate for a time then reenter tissues and become amastigotes for a new reproductive cycle. Trypomastigotes are present in the blood in the early acute phase of infection and during subsequent febrile periods. 12 Among the triatomid species incriminated as vectors are Panstrongylus megistus, Triatoma infestans (southern South America), T. dimidiata (Central America) and Rhodm’us prolixus (northern South America and Central America). Both domestic and wild animals, including dogs, cats, pigs, armadillos, and rodents serve as reservoir hosts. The second American species, T. rangeli, is morphologically more like the African trypanosomes than it is like T. cruzi. However, in its choice of a vector, a genus of triatomid bugs, it resembles the latter. The life cycle differs from that of T. cruzi in the following aspects: the metacyclic trypomastigotes in the vector gain access to the vertebrate host through the bite of the bug; no amastigote stages have been found in the vertebrate host; and trypomastigotes may be found in blood at any stage of the infection. T. rangelz' has been reported from northern South America and from Central America and parasitizes wild and domestic animals as well as man. In the vertebrate host, it appears to be non-pathogenic. REFERENCES CITED Bray, R.S., 1974: Leishmania. Annual Rev. Micro. 28:199-217. Hoare, C.A., 1972: The Trypanosomes of Mammals. Blackwell Scientific Publications, Oxford; F.A. Davis, Philadelphia. Hoare, CA. and Wallace, F.G., 1966: Developmental stages of Trypanosomatid flagel- lates: a new terminology. Nature 212: 1395. 13 LIFE (YCLE of— Amastigote forms in cell Invasion of recticulo- endothelial cells Injected into skin Promastigote forms in proboscis . (infective stage) Migration to proboscis Reproduction in midgut Leishmania Reproduction and invasion of other cells \ L tropics: lymphoid tissue of skin L. donovani: visceral organs L. brasiliensis: skin and mucous membranes MAN Amastigote forms in cell (diagnostic stage) FLY Ingestion of parasitized cell Transformation to promastigote stage V 14 lIFE CYCLE of— Trypanosoma brucei I._b_. gambiense and IE. rhodesiense Trypomusligolc in blood. lymph (eventually invade central nervous system) Injected by Fly during bite MAN Dividing form in blood. lymph and spinal fluid Trypomasligote in blood _:§’$}mm’“ "w W Metacyclic lryponmsligolc in salivary gland (infcclivc smgu) y. wit Mulnplms In salivary gland (.0 . Epundsligolu stage In salivary gland FLY 15 (diagnostic slugs) lngcsled Multiplirs in midgul Migrates to salivary gland lIFE (YClE of- Igypanosoma cruzi Amustigotc smgc in tissue Penclrules various (issues (‘ell rupturcs. lrypomusligotcs lihcrulcd MAN Enters bne wound made by bug Meucyclic Irypomdstigotc (diagnostic slagc) ? W 4 (mfecnve stage) passed in feces of bug lngcsled BUG Trypomustigotc in blood Amastigote dividcs by binary fission M|grutrs to hindgul Epimasrigote stage in midgul 16 FILARIA The life histories of the various species of human filaria are similar except for the specific arthropod host and the location of the adults with- in the human body. These blood nematodes differ from the intestinal species in that (l) the diagnostic stage is a prelarval form called a micro- filaria, and (2) there is no external environment period. Most of the struc- tural details have been included in the drawings of the microfilariae but drawings of the other stages are more diagrammatic. Within the group, the diagnostic and infective stages have been drawn to scale, and to a lesser degree, the adults. Passage through the arthropod host is necessary for transmission of the infections. For example, microfilariae in transfused blood will circu- late in the recipient’s peripheral blood, but cannot cause infection and will die within a relatively short time. Within the human host, the worms mature slowly, requiring several months to a year before diagnostic stages (microfilariae) can be demon- strated. The location of adults varies with the species (see Table II), but microfilariae are found in the peripheral blood in all species except Onchocerca valvulus and Dipetalonema slreptocerca, where they are found in the cutaneous tissues. Recently, microfilariae of Mansonella oz— zardi have been found in the skin as well as in the blood (Moraes, 1976). The appearance of microfilariae in the blood is periodic in certain species (Wuchereria bancrofti, Brugia malayz’, and Loa 10a) and nonperiodic in others (Dipetalonema perstans, Mansonella ozzardi, and the South Pacific strain of W. bancrofti). The reasons for this periodicity are not clear. The arthropod host may be a species of mosquito (W. bancroftz' and B. malayi), of flies (0. valvulus and L. 10a), or biting midges (D. perstans, D. streptocerca, and M. ozzardz'). There is no multiplication of the filariae within the vector as occurs with the blood protozoa. The ingested micro- filariae penetrate the stomach wall of the insect after losing the sheath, if one is present, and develop to the infective third stage larvae in the thoracic muscles. The infective larvae then migrate to the proboscis, and when the insect bites again, they actively move down the proboscis to the skin sur- face and probably enter the human host through the bite wound. The development within the insect is influenced by such extrinsic factors as temperature and humidity. The average developmental time and some of the chief vectors for each species are included in Table II. Several species of arthropods may be involved as intermediate hosts for the filariae, but man is the usual definitive host in most instances. D. 17 perstans has been reported in the gorilla, L. [0a in the baboon (although its role as reservoir host is yet to be proved), and B. malayz' has been re- covered from cats and monkeys. REFERENCES Moraes, MAP. 1976: Mansonella ozzardi in skin snips. Trans. Roy. Soc. Trop. Med. and Hyg. 70(1):l6 18 6l TABLE II CHARACTERISTICS OF FILARIAE W. bancro fti B. malayi L. loa M. ozzardi D. perstans D. streptocerca 0. valvu/us Georgraphical Tropical and East Indies, West and South and Africa, South West and Africa, Central Distribution subtropical Southern Asia Central Central and Central Central and South areas Africa America America Africa America 41° N - 28° s Arthropod Host Mosquitoes: Mosquitoes: Tabanid flies: Midges: Midges: Midges: Black flies: Culex sp. Mansonia sp. Chrysaps sp. Cu/icoides sp. Cu/icoides sp. Culicoides sp. Simu/ium sp. Aedes sp. Aedes sp. Anopheles sp. Mansonia sp. Anopheles sp. Developmental Times: ArthrOpod 14-15 days 6—7 days 10-12 days 7-9 days 7-9 days Probably 8-9 days Man Approx. 1 year Approx. 1 year Approx. 1 year Approx. 1 year Approx. 1 year 7-8 days Approx. 1 year or more Probably 1 year or less Location in man: Adults Lymphatics Lymphatics Subcutaneous Mesentery, Mesentery, Subcutaneous Subcutaneous tissue body cavities perirenal and tissues tissues retroperitoneal tissue Microfilariae Blood Blood Blood Blood Blood Skin Skin, subcutan— (skin) eous tissues Periodicity of Microfilariae Nocturnal Nocturnal Diurnal Nonperiodic Nonperiodic Nonperiodic Nonperiodic lIFE CYCLE of— Wuchereria bancroffi d4 3 Nicmfi l arise Adults in lymphatics Lymphllica Circulglion MAN Enter: skin through mosquito bile-wound Microfilariu in blaod (diagnostic stage) 3;“! sun: larv- (inlective alike) lngestei —‘ Migrates to head andproboscis MOSQUIIOES Sths sheath; penetrates stomarh wa|| Thoracic muscles \ lst_ sun larva ® 20 “F! (“H of— 0' \licrofillrl Ie Lymph-lies Adults in lymphatics CircuI-tion MAN Enters skin through mosquilo bite wound 3nd. lllKe Int-v. (lnl‘ective stun) Mlgntu m hm M 0 S 0 U l l 0 E S “”5““ and proboscis 3rd. stake larv: Sheds sheath; penetrates stomnch wall Thoracic muscles \ 151.:[3z2llrvn/ @ 21 lIFE CYCLE of— “icml'ilari ue Adults in subcutaneous tissue Circul uinn MAN Enters skin [hm-ugh Micmfilaria in blood 3rd. stage larva (diagnostic stage) (infective suge) F H muted \ligmea to head 3nd proboscis EB Sheds sheath: eneuu at lunch wall 3rd slage harm 9 es 0 \ Thoracic muscle: \ 15.. um larvn / ® 22 lIFE CYCLE of— Mansonella ozzardi \licrnfilariae / Adults in body cavities, mesenlerv. eic. Eplers skin lhmugh fly bile wound Circulation / MAN \licrnfilarxa in hlnnd 3rd. slag: larva (diagnostic sxazo) (infective stage) Miracles to hand F [Y lnzesled and proboscis Penelrales stomach wall 3rd. stage larva Thoracic mu scles \ 13!. stage larva @u 23 LIFE CYCLE of— Dipetalonema persfans Adults in mesentery, peritoneal cavity, etc. Enters skin through fly bite wound Circulation MAN Microfilnria in blood 3rd. stage larva (diagnostic stage) (infective stage) Migrates to head lngested and proboscis FLY 3 d gm 3 larva Penetrates stomach wall r » s Thoracic muscles 15!. stage larva 24 NH 0le of- Dipefa/onema sfrepfocerca Adulxs in when mucous [issue M icrul‘iluriuu Enters skin through fly hilc wound M A N Skin erml‘ilnrin in \km 3rd. slugz‘ Iu rvu Mixlgnm‘nc mun) . ‘ (infective sluge) w \R Migrates to hcad and préboscis llulcslfll \f] Smflt‘ larva I’clwlrulcs slulllm'll wall Thoracic musclu lst. filugc lurvu / 25 “FE CYCLE of— Onchocerca volvulus o' 8 \ mm. in lubcunneoul nudul: ”"mm'm" Sub: mimeom financ- MAN Finns akin lhlolurh fly bin.- wound Micmfil-dl in skin 1d mg: larv- ,(di‘lunonic Inge) (infeclive lune) \Iigme- In head lngemd Ind pmhuci. F [Y Penelrlln slam-ch ull ; 3rd stage 1mm 1mm: muscles \ In an: hm DRA CUNCUL US Dracunculus medinensis is often grouped with the filariae, but since its life cycle differs significantly from the life cycles of the filariae, it is discussed separately. The diagnostic and infective stages, however, are drawn in proportion to those of the filariae. The sizes of the adult Dra- cunculus worms are relative to each other, but not to filariae adults. D. medinensis, or the guinea worm, is probably the “fiery serpent” referred to in biblical writings and is a parasite of man in Africa and Asia. Man acquires infections with Dracunculus by drinking water contami- nated with the arthropod host which contains the infective larvae. Most of the other blood parasites are acquired through the bite of the vector. After slowly maturing in the loose connective tissue or serous cavities, the gravid female migrates to the superficial cutaneous tissue. First-stage larvae are liberated from the female worm directly into the external environment, in this case into water, through an ulcer or blister which forms on the skin over the anterior end of the worm. The free-swimming larvae are ingested by a species of Cyclops and mature in the body cavity in about 3 weeks. In many respects, Dracunculus differs from other blood and tissue parasites. Although it requires an intermediate host for completion of its life cycle, like the filariae, it is markedly different from other blood and tissue parasites in its choice of host (a crustacean rather than a species of Diptera), mode of entry into both arthropod and man (by ingestion), and its free-swimming larvae. Man is not the only definitive host of Dracunculus. Species other than medinensis have been reported from both domestic and wild animals — dogs, cats, foxes, mink, and even horses and cattle. Infections have been reported in fur-bearing animals in North America. 27 “FE (YClE of— Dracunculus medinensis o4 v», Adults in connecyiye tissue Penetrates intestinal Wall Of b0d)’ clvmes Gnvid 9 migrates to superficial cutaneous tissue MAN ingested within Cyclopl Lam escapes from skin lesion 3rd stage larva (diagnostic stage) ‘ ‘ . (infective stage) / CYC LOPS Freeqwimming in water / lnmted Penclrates into body caviiy 28 Ill. TISSUE PARASITES The tissue parasites of man include both helminths and protozoa. Some of these species are considered human parasites (for example, Trichinella, T oxoplasma); others are accidental human parasites (for example, T oxocara canis, Echinococcus sp.) A number of parasite species have been reported as tissue parasites of man in different parts of the world. In this manual, however, only those species which are more commonly encountered in the United States are presented. Some of the organisms included with the group of blood parasites are tissue inhabitants, for example, Leishmanz'a sp., T. cruzi, and Dracunculus. (Even malaria develops in tissue in its exoerthrocytic stage.) Since they either have an erythrocytic phase or are closely related to other blood species, however, they have been included with the blood parasites rather than with the tissue parasites. . HELMINTHS The three species of helminths included here inhabit human body tissues in the larval form. The adults of all three are normally inhabi- tants of the intestine of the definitive host. Man may be an intermediate host (as for Echinococcus) or both an intermediate and a definitive host (as for Trichinella) or simply an accidental host (as for Toxocara). In all three charts, the cycle in man has been left open to indicate the “blind alley” ending of the parasites in humans. Trichinella spiralis T. spiralis is a nematode parasite which goes through both adult and larval stages within a single animal host but two hosts are necessary for the infection to continue. T. spiralis is found everywhere in the world, except in the tropics. The cycle is a relatively simple one, with a short adult life—span and a considerably longer larval life. The host, which is both the definitive and intermediate host, may be any carnivorous or omnivorous animal, but it is chiefly, man, hogs, rats, bears, foxes, dogs, and cats. From the standpoint of man, the hog is the primary source of infection, and the life cycle chart has been prepared on this basis. It includes only the most important and basic steps. The general consensus is that the infection is maintained in swine primarily through their ingesting the infective larvae in meat scraps 29 (usually pork) in uncooked garbage. This swine-to—swine transmission is shown in the life cycle chart. The cycle in man in initiated by ingestion of meat (pork) containing encysted larvae (diagnostic and infective stages). In the intestine the liberated larvae mature very rapidly, and by the fifth day the females begin to deposit larvae, a process which continues for about 4 weeks or longer. The males live for a relatively short time and are usually passed soon after fertilization takes place. The young larvae reach the tissues by way of the lymphatics and blood. Although they are carried to all parts of the body, they ordinarily develop only in striated muscle. They may begin to encyst in about 3 weeks, and the cyst often starts to calcify as early as 6 months and is usually completely calcified within 18 months. Most of the encysted larvae probably die within 1 to 2 years after infection. Larva Migrans Human infections with larvae of nematode parasites of lower animals are called larva migrans. Larva migrans may be caused by many dif- ferent species of parasites and may be either cutaneous or visceral, de- pending on the body area affected and the parasite species concerned. CUTANEOUS LARVA MIGRANS Cutaneous larva migrans may be caused by several species of hel- minths, but the filariform larvae of the dog and cat hookworm are the most common causes. The cycle in the normal hosts is the same as that for human hookworms (included in the intestinal helminth series) and is not included here. In man the larvae cannot proceed further than the cutane- ous layers in the region of penetration. VISCERAL LARVA MIGRANS The principal agent of visceral larva migrans appears to be the dog ascarid, Toxocara canis. The life cycle of T. canis is included here as representative of the larva migrans group. T. canis is an intestinal nematode with a life cycle similar to that of Ascaris lumbricoides, the human ascarid species. Its distribution is cosmo- politan. The one—celled egg (diagnostic stage) is passed in the feces of the dog and develops in the external environment to the embryonated stage (infective stage). When ingested by the normal host, these embryonated eggs hatch in the intestine, and the liberated larvae undergo a lung migra- 30 tion before maturing in the lumen of the intestine. Toxocara canis infec- tions may be transmitted from mother to puppies in utero. Man becomes an accidental and abnormal host by ingesting the embryonated eggs. In the human intestine, the eggs hatch and the larvae penetrate into the mucosa and the circulation. However, since they are not in a normal host, they do not complete the lung migration but are filtered out in various organs, chiefly the liver. They remain immature and eventually die in the tissue. The infection is more common in children than in adults and is characterized by a persistent high eosinophilia. Echinococcus Echinococcus spp. (E. granulosus, E. multilocularis, and E. vogeli) are the etiologic agents of hydatid disease in man. E. granulosus is widely distributed in temperate and subtropical regions and other areas where sheep, cattle, and hogs are raised; E. multilocularis is found in Europe, Russia, and North America; and E. vogelz’ has been reported from Central America and Northern South America. Only the larval stages infect humans, and the hydatid cysts may be found in various tissues, chiefly liver and lungs. As with most cestodes, the normal life cycle of Echinococcus. sp- involves two hosts, definitive and intermediate. The adults are found iii the intestines of various carnivora, especially dogs and foxes, and larvae develop in sheep, cattle, orswine (E. ’ granulosus) or in rodents (E. multilocularis and E. vogeli). The lifexhis- tories of the three species are similar elxcept for the. choice of intermediate host, so only that of E. granulosus is representedshe‘re. The eggs of the worm (diagnosticlstage) are passed in the feces of the definitive host. They are ingested by the intermediate host, in which the infective larvae (hydatid cysts) develop. The larval growth usually requires about 5 months. These larval forms differ from those of other human cestode infections in that multiple rather than single scoleces develop within the cyst. When hydatid ysts containing the scoleces are ingested by carnivores, adult worms mature in the small intestine in about 7 weeks. Man may become an accidental intermediate host by ingesting the eggs in contaminated materials. In addition to Echinococcus larvae, man may also become the inter- mediate host of the larval stages of Taem’a solium, which in the adult stage normally infects the human intestine. The extraintestinal phase of the T. solium cycle in man has been presented in the chart included with the intestinal helminths and is not repeated here. 31 PROTOZOA Toxoplasma gondii, a protozoan belonging to the class Sporozoa, is one of the most important tissue parasites of man. Another serious infection is primary amebic meningoencephalitis caused by free-living amebae. Toxoplasma gondii T. gondii is widespread in a variety of vertebrate hosts, including man. Most infections appear to be asymptomatic or only mildly symptomatic, but serious, often fatal conditions may occur, especially in newborn babies as a result of congenital transmission. Toxoplasma is a coccidian parasite (F renkel et al., 1970) and has a life pattern similar in some respects to those of other species of this group of Sporozoa. Felinidae are the only recognized definitive hosts, with mice and other small rodents as the common intermediate hosts. Because of its close association with man, the domestic cat plays an important role in the transmission of toxoplasmosis. In addition to serving as an intermediate host and experiencing the clinical problems associated with the asexual development of the parasite, the cat also serves as the definitive host in which the sexual cycle occurs. As described by Frenkel et al. (1970), the cycle is as follows: in some circumstances, the cat’s initial infection results in the Toxoplasma organisms invading the intestinal epithelium, where they undergo a cyclic asexual development similar to that of other coccidian species and produce trophozoites and schizonts resembling those seen in Isospora infections. T. gondii, like Isospora, also has a sexual reproductive phase in which macrogametocytes and microgametocytes are formed in the mucosa] cell. These develop into gametes, which, when fertilized, produce oocysts. The oocyst is passed in feces, and matures to the infective stage with two sporocysts, each con- taining four sporozoites. After being ingested by an intermediate host, the sporozoites are liberated from the ob‘cyst, invade various body tissues by way of the circulation, and multiply asexually. These tachyzoites (rapid- growing trophozoites) differ from those in the cat intestinal mucosa in appearance and growth pattern. They divide by a process called endodyo- geny in which two daughter cells are formed within the parent cell. No schizogony occurs, and only a tachyzoite stage is present. Tachyzoites proliferate in the tissue during the acute phase of the infection. If the animal survives and immunity develops, cysts containing numbers of bradyzoites (slow-growing trophozoites) are formed and the infection 32 becomes chronic. T. gondii, unlike most parasites, has two infective stages in its normal life history: mature ob‘cysts and tissue cysts containing bradyzoites. In addition to ingesting ob‘cysts in cat feces, intermediate hosts may become infected by ingesting cysts in tissues of other intermediate hosts. In the body, the bradyzoites are liberated from the cyst, penetrate tissue cells, and proliferate as tachyzoites. The growth pattern is the same as in infections initiated by the ingestion of ob'cysts. Almost all warm-blooded animals are susceptible to infection with T. gondii. Intermediate hosts include rodents, pigs, sheep, cattle, man, and cats. Rodents, however, are probably the most important and most common intermediate host. In nature, toxoplasmosis is maintained in the rodent population through cannibalism, thus perpetuating and spreading the infection. Man probably acquires toxoplasmosis by ingest- ing mature o'ocysts in material contaminated by cat feces or by eating meat such as pork, lamb, or, possibly, beef containing cysts. As with the diagrams for the helminth species, the diagram of the T. gondii cycle in man has been left open to denote the “blind alley” ending of the parasites in humans. F tee-Living Amebae Species of Naegleria and Acanthamoeba, free-living amebae species normally inhabiting soil and water, have been incriminated as agents of primary amebic meningoencephalitis in humans. The organisms apparently gain access to the body through the nasal passages or, occasionally, the eye, and possibly, through wounds. Most human infections have occurred in persons with histories of swimming in contaminated fresh water — ponds, small lakes, even swimming pools — where the water is warm and stagnant and, often, algae growth is heavy. Amebae have also been isolated from brackish and salt water, so infections may be acquired by contact with salt as well as fresh water. No man—to- man transmission has been clearly demonstrated, although nosocomial infections have been suspected. Trophozoites, rather than cysts, are the infective stages for man. After entering the body, the amebae migrate to the brain and may be found in brain tissue and cerebrospinal fluid. Only trophozoites are found in brain tissue lesions in infections with Naegleria, whereas both trophozoite and cyst stages are found in tissue lesions in infections with Acanthamoeba. The amebae affect the brain tissue directly, producing symptoms of 33 meningitis. Naeglerz'a causes sudden acute, fulminating disease, which leads to death within 7 to 10 days. Acanthamoeba sp. are believed to cause chronic disease with a prolonged course and relatively insidious onset. In addition to causing meningoencephalitis, Acanthamoeba sp. also cause ocular keratitis and other eye infections. The morphology of the free-living amebae species that parasitize man varies considerably. Both Naegleria and Acanthamoeba have trophozoite and cyst stages, but the Naeglerz'a species also have a temporary flagellated stage that develops in response to altered environmental conditions. The life cycle presented here as representative of the group is that of Naegle- ria fowleri, a speciesresponsible for fulminating disease in man. As with similar infections, the life cycle in man is left open to denote the “blind- alley” ending. REFERENCE Frenkel, J .K., Dubey, J .P., and Miller, N.L. 1970: Toxoplasma gondii in Cats: Fecal stages identified as coccidian oocysts. Science 167:893-896. 34 lIFE»CYCLE of— Trichinella spiralis Larva deposited lrl mucosa Clrculalion um released in small Intestine Encysted larva l" s mated musde (diagnostic stage) Lam released Larva deposited in small intestine in mucosa SWINE OTHER CARNIVORES cammm Ingested Encyslcd larva m striated muscle (diagnostic stage) ‘- Encysted larva in ' striated muscle (infective stage) MEAT (PORK, etc.) 35 UFE CYCLE of— Laxocara canis Circulation MAN Larvae migrate in eye. 13”“ ““0" liver, lung. brain. other omns in intestine Lungs \ - Circulation Trachea /'l/ / Transplacental \I ‘ transmission " to offspring Pharynx ,;\\l Larvaehalch Q!) In intestine lngested V Adultsin lumen of small intestine Eggs in feces Embryonaled egg Fertilized - l cell With 2nd stage larva (infective stage) EXTERNAL ENVIRONMENT 2 - cell stage ll“ “Cl! If— Echinococcus grandam Cheddol 0min: Inch: I pemnle- iuun'nl VIII 5 ' . "ydddcy-i- ma. 1-... an. Ono-pm hacke- plat-u intestinal wall SHEEP, SWIIE, ("HE \ m. , , , dad in feces “aid :7: in wiles- Vln-I imd (AIIIVOIES '1', Add! in null inc-tin . . 1.. ..l ._. Kn: \“Ehu‘n {y x: . 37 UFE CYCLE of— Toxoelasma gondii Tachyzoltcs in tissue cell (acute phase) MAN Ecnetrates OQ tissue cells % Bradymne \ % Ingesled m pork. hmb %) /S/porozo|le c‘ g Sassyzgikics Tachyloilcs in [issue ccll / SHEEP, CATS ¥ spawn,”e OTHER VER I'EBRATLS Bradvzoutc Ingesled 'Q/ lngested INTERMEDIATE HOSTS RODENTS. PIGS Sporozouy, Bradymuc . Muluru ”my“ (infective stage) (Infecnv: stage) conlulmng sporozolles EXTERNAL CAT Mcg% showman: ENVIRONMENT (Definitive Host) \ Obcysls With sporocysts 9‘ I l *h’ z * Oocyn thh “ c‘uifi’mflo mma ure 5: 120“ 5 $ urubizsls a p fi Q 16 J , i \ c \ j W (diagnostic stage) - Femiizauon lmmulu oécys! @ 38 UFE CYCLE of- Naegleria fowleri Penetnles nasal mucosa MAN Trophozoites m CNS EXTERNAL ALTERED ENVIRONMENTAL CONDITIONS p Trophozoite kr' Flagllated sta ( empom’y ENVIRONMENT 39 4M4174679