THE ETIOLOGY OF MALABTAL DISEASES. 429

On the Question of Priority with Regard to certain Discoveries upon the ./Etiology of Malarial Diseases. By George If. F. Nnttall, M.A., M.D., Ph.D., University Lecturer in Bacteriology and Preventive Medicine, Cambridge.

THOUGH it has long been a popular belief in certain countries that is communicated to man by means of mosquitoes, experimental proof was lacking until a recent date. The history of the -malaria theory has been amply dis- cussed elsewhere by the writer, to whose papers the reader is also referred for a detailed description of the experimental work on the part played by mosquitoes in the propagation of malarial diseases.1 It is not the object of this paper to discuss these matters in detail. Persons who read the medical literature of but one country will naturally become biassed in their judgment. This ac- counts for the fact that at present different investigators receive the credit of having definitely established the part played by mosquitoes in malarial diseases. In view of the confusion which will naturally result from the claims made i Nuttall, G. H. i\ (1899-1900). I. " On the Role of , Arachnids, and Myriapods as Carriers in the Spread of Bacterial and Parasitic Diseases of Man and : a critical and historical Study;" 'Johns Hopkins Hospital Reports,' vol. viii, pp. 1—154, 3 plates (Bibliography). II. "Die Mosquito-Malaria-Theorie," ' Centralbl. f. Bakteriologie,' vol. xxv, pp. 162— 170, 209—216, 245—247, 285—296, 337-346 (Bibliography). III. " Neuere Forschungen iiber die Rolle der bei der Verbreitung der Malaria: Zusammenlass,endes Referat;" ' Centralbl. f. Bakteriologie,' vol. xxvi, pp. 140—147, and vol. xxvii, pp. 193—196, 218—225, 260—264, 328—340 (exhaustive Bibliography). 430 GEORGE H. F. NUTTALL.

in vai'ious quarters, it seems eminently desirable to give a brief impartial summary of the experimental work which has been done, relying solely upon published researches, these being cited in their chronological order. With the facts thus marshalled before him every reader is at liberty to draw his own conclusions. The study of the liEemocytozoa begins with the discovery by Ray Lankester in 1871 of Drepanidium ranarum. Human malarial parasites were seen, but their significance not comprehended until Laveran published his investigations in November, 1880. Following upon, the fundamentnl work of Laveran, the most important discovery was that of Golgi (November, 1885), who demonstrated the relationship exist- ing between the life-cycle of the parasites within the human body and the occurrence of the febrile attack. "With regard to these investigations there has never been any dispute on the question of priority, but this is far froni being the case with the discoveries which followed. Any further disputes regarding the priority of subsequent discoveries should be disposed of by such a chronological record as that which follows, in which not only the year, but also the month and even day of publication are given.

Chronology relating to certain of the more Im- portant Recent Researches on Malaria.

1893 and 1895, Sacharoff demonstrated the presence of chromatic substance within the "flagella" of certain avian parasites by means of the Romanowsky stain. December 17th, 1895, Ross observed the process of "flagellation " of crescentic parasites to occur in the stomach of mosquitoes ( not determined) fed on the blood of a malarial patient. 1896, Bignami and Dionisi report the negative results of two experi- ments made in 1893-4 with mosquitoes (species uncertain) collected in malarious localities, the insects being permitted to bite healthy per- sons. They attribute the failure of the experiment to the dispersion of THE ETIOLOGY OF MALARIAL DISEASES. 431

the insects in the room where they were liberated, and to the experiment not having been continued long enough. They cite Calandruccio as having observed the degeneration of malarial parasites in the stomach of mosquitoes (species not stated).

November 13th; 1897, MacCallum, in Baltimore, found that the "flagella" of Halteridium and of Eestivo^autumnal parasites constitute the male element, and serve to impregnate the "pig- mented spheres" or female element. In the case of Halteridium the impregnated spheres became con- verted into motile " vermicules." This transforma- tion was, however, not observed in the human parasites. December 18th, 1897, Ross fed mosquitoes upon human blood containing crescentic parasites. The ex- periments were made at Secunderabad, and were reported upon at the time as follows : After examining hundreds of mosquitoes fed on malarial blood, always with negative results, he obtained a few which belonged to a species with spotted wings, which he had hitherto not used. As Eoss distinctly describes the egg of this species, there is no doubt whatever but that he was dealing with a species of Ano- pheles. The insects were bred from larvae, and fed •with blood containing crescentic parasites. Pour to five days later peculiar pigmented cells were obsei-ved lyiug within the walls of their stomachs. These cells were round or oval; they measured 12—16 /x on the fourth, and 20 fx on the fifth day after feeding, and the pigment they contained was similar to that within the malarial para- sites in the blood upon which the insects had been fed. Such bodies could not be found in control mosquitoes. Eoss concluded that he had found the mosquito which served as a host for the parasite. February 26th, 1898, Eoss refers again to his experiments with crescentic parasites. After examining some scores of " dapple-winged" mosquitoes unfed or fed with healthy blood, all the results were negative until 432 GKOfiOK K. F. NTTTTALT,. " at last two of this species were, persuaded to feed on a patient with crescents. One of them was killed next day; no pigmented cells could be found. The second was killed forty-eight hours after feeding ; numerous pigmented cells were pi'esent. They were all small, much smaller than epithelial cells, ovoid, about 7 n in the major axis, and each contained about twenty granules of typical pigment, which were often arranged circmnferentially, just as in the malarial parasite." Though it is not stated in this publication that he raised these mosquitoes from larvae, reference to Boss's previous paper (p. 1786) will show this to have been a part of the method he employed.

Experiments with Tertian Parasites.—"A hundred or more grey or 'barred-back' mosquitoes, unfed or fed on healthy or crescent blood, have been dissected without finding the pigment cells. At last one was observed feeding on a patient whose blood that morning had been seen to contain numerous mild tertian parasites." Killed on the third day, the contained many pigmented cells measuring 8—25 p, (Ross subsequently discarded this experiment, as it was possible that the insect which was not raised from the had become infected with some other parasite.)

May 21st, 1898, Experiments on Proteosoma.—Work- ing in Calcutta, Ross observed the development of Proteosoma in a species of (subsequently determined as C. fatigans, Wied.), the insects being fed on the blood of infected crows, larks, and sparrows. The parasites found in the external coat of the insects' stomachs measured 6 fi after thirty hours, 60 (i after six days. "Successive feeds by the same mosquito on the same bird are followed by fresh crops of young coccidia. . . . Similar pigmented cells" had been previously observed in mosquitoes fed on human parasites. Ninety- four per cent, of the mosquitoes fed on blood containing mature Proteosoma became iufected. September 24th, 1898.—Manson reported to the British THK ^ETIOLOGY 01' MALAHIAL DISEASES. 433 Medical Association Meeting at Edinburgh (July) on behalf of Boss regarding further experiments with Proteosoma. These observations showed that the encapsulated parasites, on reaching a certain size, rup- tured and emptied their contents into the coelom of the insect. The contents of the ruptured capsules consisted of minute spindle-shaped bodies, and these bodies sub- sequently accumulated in the salivary gland of the insect. When this had occurred the insects were capable of communicating the proteosomal to healthy birds. Of twenty-four sparrows exposed to the bites of insects fed on matnre parasites, twenty-two became infected. October 1st, 1898, Grrassi reported that he had reason for suspecting three species of Culicidae as being carriers of malarial infection, claiming that they were confined in their geographical distribution to those regions where malaria was prevnlent in Italy. The three species were Culex penicillaris, Anopheles claviger (syn. A. maculipennis), and a purported new species, Culex malariae.1 It has since been proved that only 1 In his paper in the 'Policlinico' (October 1st, 1898), Grassi writes: "In conclusione, io sono d'avviso che it Culex penicillaris e 1' Anopheles claviger o per Io meno il Culex penicillaris, fors' anche il Culex malaria, nella malaria si comportano come le zeeca nella febbre del Texas." Grassi therefore makes a misstatement in a later paper (December 1st, 1900) when he writes, " Proclamai come iudiziati due specie di culex, ma sopratutto 1'Anoplieles olaviger." It is curious that Grassi should subsequently have continued to lay stress upon the geographical coincidence having led him to the discovery of Anopheles claviger being a host of malarial parasites, for two out of three species which he for this reason supposed must be hosts were afterwards proved not to be such. He certainly considered A. claviger at first to be of quite secondary importance; we have his own words for it: " Certi casi di malaria sviluppatisi in Settembre a Locate Triulzi, nei quali gli Anopheles di certo o non puusero o soltanto rarissime volte, den unciano decisamente come trasmissore il Culex penicillaris, enorma- mente comune in tutti i luoghi malarici." (The italics are Grassi's.) It is but fair to Ross to state here that Grassi in his paper of the 1st of October refers to the experiments made by Smith and Kilborne upon Texas . fever; and by Ross upon avian malaria as having been a " forte argumento " 434 GEORGE H. F. NUTTAIJ,. the second of the three species named can serve as a host for human malarial parasites. The coincidence in the geographical distribution of ague and malaria-bear- ing mosquitoes in Italy, as claimed repeatedly by Grassi, has been disproved by Celli. The claim that this geo- graphical agreement would probably be found to hold in other parts of the world has been disproved by Nut- tall, Cobbett, and StrangewaysPigg (1901) in England. We cannot, therefore, accept Grasses statement that he discovered the malarial mosquito because of its geo- graphical distribution, pretty and ingenious as the hypothesis seemed in the beginning. It seems certain that Grassi was after all entirely guided by Ross's pub- lication of December 18th, 1897, in which he describes an insect with spotted wings and eggs like those which characterise Anopheles.

November 6th, 1898, Infection Experiment on Man.— Grassi mentions that Bignami had made an infection experiment by means of inosquitoes (the three species above named were employed) collected at Maccarese, a malarious locality. The result was positive in this case, the person acquiring sestivo-autumnal fever. (Several infection experiments were subsequently car- ried out by Bignami, Bastianelli, and Grassi in colla- boration, these being reported in various papers of later date. The first experiment did not prove which species harboured the parasites, and of itself was insuf- ficient to establish the theory on a firm basis.) December 4th, 1898, Bastianelli, Bignami, and Grrassi observed the development of crescentic parasites in Anopheles claviger, the appearances correspond- ing to those described by Ross for Proteosoma on the in favour of the mosquito-malaria hypothesis. In the paper read on the next day at the Accademia dei Lincei, under the same title as that which appeared in the ' Policlinico," Grassi omits to mention Ross, though he refers to what was known regarding Texas fever. The paper, published in the ' Transac- tions ' of the Accademia, differs in several respects from that which appeared jn the 'Policlinico.' THK ETIOLOGY OP MALARIAL DISEASES. 435 fourth day in Culex. Referring to his experiments with, human parasites, they write, " Verisimilmente i due mosquitos coli ali macchiate nei quali il Ross in India trovo stadi di sviluppo simili a quelli del proteosoma (3° giorno circa) appartenevano pure alia specie An ophel es claviger, Fabr." (This statement is of interest in view of Grassi's subsequent claim that Ross might very well have been working with insects belonging to the genus Culex, and not with Anopheles at all.) They, more- over, consider that Ross had not certainly determined the development of the crescents in his mosquitoes, for his observations had been broken off at too early a date; besides which the insects might have infected themselves with hsematozoa from some other . We have seen that the latter supposition is unwarranted, because Ross's Anopheles were raised from larvse. Moreover they themselves neglect to state that they raised their Ano- pheles from larvae, so we must presume that they did not. Infection Experiment on Man.—In a foot-note to the above publication it is reported that the authors had successfully infected a person with tertian fever by means of infected A. claviger, collected at Maccarese. December 22nd, 1898, Grassi, Bignami, and Bastianelli follow the development of crescentic parasites in Anopheles claviger to the formation of "sporo- zoites," the escape of the latter into the coelom of the insect, and their accumulation in the salivary gland. The development was found to be slower at 20° to 22° than at 30° C. The fully developed capsules measured 70 /u, the sporozoites measured 14 ju. The process of development, the size of the fully developed capsules, and of the sporozoites, were the same as Ross had observed in Proteosoma. The development of tertian parasites was observed to take place in A. claviger up to the fifth day. February 2nd, 1899, Koch published a preliminary note 436 GEORGE H. F. NUTTALL. upon the results of the investigations conducted by the German Malaria Commission, consisting of himself, E. Pfeiffer, and H. Kossel. Further details will be found in a publication which appeared September 8th, 1899. The Commission observed the development of Pro- teosoma in Culex nemorosus, from the formation of the " vermiculi" described by MacCallum for Halteri- dium to their appearance in the salivary gland of the insect. The pi'ocess of fertilisation was found to occur in Proteosoma, as MacCallum had found for Halteri- dium and human crescentic parasites. Healthy birds were successfully infected by means of infected insects. The later publication, which is illustrated by excellent microphotographs, completely confirms the observations of Ross and others. February 5th, 1899, Grassi, Bignami, and Bastianelli observe the development of quartan parasites in A. claviger. Eoss (September 2nd, 1899) observed the development of quartan parasites in a species of Anopheles in Sierra Leone. January 23rd, 1899, Daniels reported to the Royal Society that he had been able to confirm Ross's observations with Proteosoma. He followed their development in a species of Culex, and successfully infected healthy birds by means of infected iusects. He added nothing to what Ross had already found, April 19th,1899,Bastianelli and Bignami reported further studies upon the development of tertian parasites in Anopheles claviger, and describe three successful infection experiments on man by means of A. claviger previously fed on tertian parasites. May 7th, 1899, Grassi, Bignami, and Bastianelli report to the Accademia dei Lincei that they had observed the development of tertian and crescentic parasites in Anopheles bifurcatus. June 18th, 1899, Grassi observed the development of tertian and crescentic parasites in Anopheles fHE JfiTIOLOGt OF MALAEIAL DISEASES. 437 pseudopictus, but not in various species of Culex. The latter result again obtained later (October 4th, 1899). June 28th, 1899, Ross stated that Proteosoma scarcely developed in Culex at 21°, and that the growth of the parasites was already slowed at 27° C. in Calcutta. The development of tertian parasites in spotted-winged mosquitoes raised from larvae was also observed (letter dated February 22nd, 1899, to Nuttall; see 'Centralbl. f. Bakteriologie,' vol. xxv, p. 908). September, 1899, Bastianelli and Bignami give a de- tailed description of tertian and crescentic parasites, the publication being accompanied by the best coloured plates hithei'to published, illustrating their development. They prove that a single infected Anopheles claviger may communicate malaria (tertian) to man. May 4th, 1900, Ziemaun, working in Cameroon, observes the development of the parasites of tropical malaria in two species of Anopheles, as also the development of tertian parasites in one species of Anopheles. He followed the development to the appearance of sporozo- ites in the salivary glands of the insects. He subse- quently (November 22nd, 1900) found that the parasites would not develop in Cimex lectularius nor in sand- . September, 1900, van der Scheer and van Berlekom, in Holland, observe the development of tertian parasites in A. claviger. September 29th, 1900,Manson reported apositive infection experiment with tertian-infected Anopheles (spec. ?) imported' from Rome, the insects being permitted to bite his son in London. October 6th, 1900, Rees reports a similar experiment to the former.

After perusing the above chronology, and remembering the question most disputed—the discovery of the develop- 438 GEORGE H. 1?. NDTTALL.

ment of human parasites in Anopheles, we must conclude that the pigmented encapsulated bodies observed by Eoss in " spotted-winged mosquitoes" at Secunderabad were cres- centic parasites in early stages of development. In his first paper Ross definitely states that he raised the imagos from larvae kept in bottles; that the parasites which subsequently developed within them contained a pigment similar to that of the parasites iu man; and his description of the insects' eggs leaves no room for doubt but that they were Auo- pheles. (In their paper of December 4th, 1898, Bastianelli, Bignami, and G-rassi even made the statement that it is extremely likely that Ross's spotted-winged mosquito was A. claviger!) The work done subsequently on Proteo- sotna quite rightly confirmed Ross in his belief. We are, hpwever, indebted to the Italian investigators named for completing the study of the further development of human parasites in various species of Anopheles, these studies being subsequently pursued by still other investigators in other countries.1 Ross is perfectly justified in laying stress upon the fundamental importance of his discoveries in the development of Proteosoma, and there can be no doubt whatever about his work having served as a guide to sub- sequent investigators. There is no denying that both the human and avian parasites referred to offer great points of similarity throughout. The assumption was, therefore, per- fectly justified that the further stages in the development of crescentic parasites such as Ross had observed at Secunder- abad would be identical with what he saw in the case of Proteosoma afterwards in Calcutta. In conclusion we must not forget to mention the name of Patrick Manson, who until recently took no part in the experimental solution of the problem, but who throughout Ross's investigations, which he stimulated, did much to further the studies which iu one direction at least have reached such a satisfactory conclusion. 1 It lias not been deemed necessary to refer to all of these. THE AETIOLOGY OF MALARIAL DISEASES. 439

PUBLICATIONS CITED. JJASIIANELLI, G., and BIGNAMI, A. (dated April 19tl), 1899).—" Sullo sviluppo dei parassiti della lerzana nell' Anopheles olaviger," 'Bullettino della R. Accad. Med. di Roma,' anno xxv, 1S98-9, fasc. 3 (reprint 28 pp.). BASTIANELLI, G., and BIGNAMI, A. (published end of September, 1899).— I. "Sullo sviluppo dei parassiti della terzana nell' Anopheles claviger." II. "Sulla struHura dei parassiti malarici e in specie dei gameti dei parassiti estivo-autunnali," 'Annali d' Igiene speri- nieutale,' N. S., vol. ix, fasc. 3, pp. 272—293 (1 col. plate), pp. 245 —257 (2 col. plates). BASILANELLI, G., BIGNAMI, A., and GKASSI, B. (meeting of December 4th, 1898).—" Coltivazione delle seinilune raalariclie dell' uomo nell' Anopheles claviger, Fabr. (Sinonimo, Anopheles maculi- pennis, Meig.); Nota preliminare," 'R. Accad. dei Lincei,' vol. vii, 2 sem., ser. 5a, fasc. 11 (reprint 1 page). BIGNAMI, A. (1896).—"La ipotesi dei parassiti malarici fuori dell' uomo," 'Policlinico,' No. 14. Also transl., "Hypothesis as to the Life- History of the Malarial Parasite outside the Human Body (apropos of an article by Dr. Patrick Manson)," 'Lancet,' vol. ii, pp. 1363— 1367, 1441—1444. CELLI, A. (November 5th, 1900).—" Beitrag zur Erkenntniss dei- Malaria- epideraiologie vom neuesten aetiologischen Standpunkte aus," ' Centralbl. f. Bakteriol.,' vol. xxviii, pp. 530—535. DANIELS, C. W. (read March 16th, 1899).—"On Transmission of Proteo- so ma to Birds by the Mosquito: a Report to the Malarial Committee of the Royal Society," 'Pioc. of the Royal Soc.,' vol. Ixiv, pp. 443— 454. GOLGI (1886).—" Sull' infezione malarica,"' 'Arch, per le Scienz. med.,' vol. x, pp. 109—135. See also ' Arch. Hal. de Biol.," vol. viii (1887). GKASSI, B. (published October 1st and 2nd, 1898).—"Rapporti tra Is malaria e peculiari insetti (Zauzaroni e Zanzare palustri); Note preliminare," 'Policlinico,' vol. V—M (reprint 10 pp.). Also (under the same title though altered) 'Rendiconti della R. Accad. dei Lincei' (meeting of, October 2nd), vol. vii, 2 sem., pp. 163—172. GBASSI, B. (June 22nd, 1899).—"Ancora sulla malaria," ' R. Accad. dei LinceJ,' ser. 5a, vol. viii, 1 sem., fasc. 12 (reprint 3 pp.). GKASSI, B. (October 4th, 1899).—" Osservazioni sul rapporto della seconda spedizione malarica in Italia presieduta dal Prof. Koch, etc.," ' Reudi- conti della K. Accad. dei Lincei,' Cl. di sc. fis.,mat. , e uat. 440 GtiOKGE H. 1\ NCTTALL.

GRASSI, B. (December 1st, 1900).—"Per la storia delle recenti scoperte sulla malaria," ' II Poliolinico,1 anno vii, No. 23, pp. 593—600. GRASSI, B., BIGNAMI, A., and BASTIANELLI, G. (dated December 22nd, 1898). —" Ulteriori ricerclie sul ciclo dei parassiti malarici umani nel corpo del zanzarone," ' Rendiconti della R. Accad. dei Lincei.' GKASSI, B., BIGNAMI, A., aud BASTIANELLI, G. (meeting of February 5tu, 1899).—" Resoconto degli studi falta sulla malaria durante il mese di gennaio," ' Rendiconti della R. Accad. dei Lincei,' vol. viii, 1 sem., ser. 5a, fasc. 3 (reprint 4 pp.). GRASSI, B., BIGNAMI, A., and BASTIANELLI, G. (meeting of May 7th, 1899).— "Ulteriori ricerclie sulla malaria," 'Rendiconti della R. Accad. dei Lincei,' Classe di sc. fis., mat., e nat, vol. viii, 1 sem., sec. 5a, fasc. 9 (reprint 5 pp.). KOCH, R. (February 2nd, 1899).—"Brgebnisse der wissenschaftlichen Expe- dition des Gelieimen Medicinalraths Professor Dr. Kocli nach Italien zur Eiforschung der Malaria," ' Deutsche med. Wochenschr.,' Jabrg. 25, pp. 69, 70. (Preliminary Report; see following.) KOCH, R. (September 8tli, 1899).—" Ueber die Entwickelung der Malaria- parasiten," ' Zeitsclir. f. Hygiene u. Infektionskr.,' vol. xxxii, pp. 1—24 (4 Tafeln). LANKESTER, RAT (1871).—"Observations and Experiments on the Red Blood-corpuscle," 'Quart. Journ. Micr. Sci.,' vol. xi, p. 389. LANXESTER, RAY (1882).—"On Drepanidium ranarum," 'Quart. Journ. Micr. Sci.,' vol. xxii, p. 53. LAVERAN, A. (November 23rd, 1800).—" Nol.e sur un nouveau parasite, etc.," 'Bull, de l'Acad. de Med. de Paris.1 LAVERAN, A. (December 24l.h, 1880).—" Un nouveau parasite trouve dans le sang des inalades utteinls de fifecre palustre;" "Origiue parasitaue des accidents de l'impaludisme," 'Bull, et Mem, de la Soo. Med. des Hopit. de Paris.' MACCALLUM, W. G.(November, 1897).—"On the Hsematozoan of Birds," ' Jolms Hopkins Hospital Bulletin,' No. SO ; also ' Lancet,' 1897 (Preliminary Note). MACCALLUM, W. G. (January, 1898).—"On the Hsematozoau Infections of Birds," ' Journ. of Experimental Medicine,' vol. iii, No. 1, pp. 117— 130 (one coloured plate). MANSON, P. (September 24th, 1898).—" The Mosquito and the Malaria Para- site," 'Brit. Med. Jouru.,' vol. ii, pp. 849—853, illustrated by figures obtained from Dr. . (Reported at the meeting of the Brit. Med. Assoc, Edinburgh, in July.) HANSON, P. (September 29th, 1900).—"Experimental Proof of the Mosquito- THE ETIOLOGY OF MALARIAL DISEASES. 441 Malaria Theory," 'Brit. Med. Journ.,' vol. ii, pp. 949—951 (two figures and one chart); also ' Laucet,1 vol. ii, pp. 923—925. NUTTALL, G. H. F., COBBETT, L., and STEANGEWAYS PIGG (January, 1901).— " Studies in Relation to Malaria. I. The Geographical Distribution of Anopheles in Relation to the Former Distribution of Ague in England" (two maps), 'Journ. of Hygiene,' vol. i, pp. 4—44. REES, D. C. (October 6tb, 1900).—"Experimental Proof of the Malaria- Mosquito Theory," ' Brit. Med. Journ.,' vol. ii, p. 1054. Ross, R. (December 17t.ii, 1895).—'Proc. of the South Indian Branch of the Brit. Med. Assoc.;' see also abstracts of Ross's letters in Manson's article, ' Lancet/ 1896. Ross, 11. (Repoit to the Director-General of the Indian Med. Service, dated September 19th, 1897, published 18th December, 1897, in England).— "On some Peculiar Pigmented Cells found in Two Mosquitoes fed on Malarial Blood" (with a note by Surgeon-Major Smyth), 'Brit. Med. Journ.,' vol. ii, pp. 1786—1788. Ross, R. (February 26th, 1898).—"Pigmented Cells in Mosquitoes," 'Brit. Med. Journ.,' vol. i, pp. 550, 551. Ross, R. (May 21st, 1898).—' Report on the Cultivation of Proteosoma, Labbe, in Grey Mosquitoes ' (Office of the Superintendent of Govern- ment Printing, Calcutta, India), 4to, 21 pages, 9 plates. Ross, R. (September 2nd, 1899).—"The Cultivation of the Malarial Quartan Parasite in Anopheles," 'Brit. Med..Journ.,' vol. ii, p. 608. SACHAROFF, N. (December, 1893).—" Recherches sur les he'mat ozoaires des oiseaux," ' Annales de I'Inst. Pasteur,' vol. vii, pp. 801—811 (une planche colore'e). SACHAROFF, N. (1895).—" Ueber die selbstandiche Bewegung der Chromo- somen bei Malariaparasiten," 'Centralbl. f. Bakleriologie, vol. xvii, pp. 374—380 (2 Tafeln). VAN DER SCHEEK, A., and BERDENIS VAN BEBLEKOM, J. J. (reprint re- ceived October, 1900).—" Malaria en Muskieten in Zeeland," 'Ned. Tijdschrift voor Geneeskunde,' vol. ii, No. 14 (reprint 16 pp., 1 plate). ZIEMANN, H. (June 21st, 1900).—"Ueber die Beziehungen der Mosquitos zu den Malm-iaparasiten in Kamerun," ' Deutsche med. Wochenschr.,' Jahrg. xxvi, No. 25, p. 399. ZIBMANN, H. (November 22nd, 1900).—" Zweiter Bericht iiber Malaria und Moskil.os an der afrikanischen Westkiiste," ' Deutsche ined. Wochen- schr.,' Jahrg. xxvi, Nos. 47 and 48, pp. 753—756, 769—772.

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