An analysis of the leishmania sandfly problem

289 TRANSACTIONS OF T H E ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE.

Vol. XXIII. No. 3. November, 1929.

AN ANAI,YSIS OF T H E L E I S H M A N I A

SANDFLY PROBLEM.

BY

S. ADLER, M.B., CH.B,

(MicrobiologicalInstitute, Hebrew University,Jerusalem.)

Since the SERGENTS, PARROT, DONATIEN and BI~GUET (1921) produced oriental sore in man by the inoculation of macerated wild sandflies the following additional evidence has been produced in favour of the sandfly theory. 1. Leishmania tropica was found to be a natural parasite of Phlebotomus papatasii (1925, 1926). This was proved by the inocdlation of herpetomonad flagel|ates from wild sandflies into man. 2. L. tropica was found to exflagellate and multiply in P. papatasii (1926, 1927) and in P. sergenti (1928). 3. L. tropica in both these sandflies tended to adopt an anterior position. This tendency was rather more marked in P. sergenti than in P. papatasii. In both species flagellates extended in some cases into the proboscis, but proboscis infections were relatively few. 4. L. tropica becomes pathogenic to man after eight days at 19° C. to 23 ° C. in P. papatasii (1926, 1927) and after six days at 27 ° C. in P. sergenti (1929). 5. Cultures of L. tropica which have become non-infective for man regain their infectivity after passing through P. papatasii (1926). 6. P. papatasii has a bacteriologically sterile alimentary tract. Col. R. K~COWLES, I.M.S., of the Calcutta School of Tropical Medicine, informs us that P. argentipes also has a sterile alimentary tract. This fact provides further evidence that members of the genus Phlebotomus are suitable hosts for leishmania. Biting insects whose alimentary tract is not bacteriologically sterile can be safely excluded as vectors of human leishmaniasis, for neither L. tropica nor L. donovani will survive for any length of time in the presence of bacteria. In the case P. sergenti, naturally occurring L. tropica has not yet been demonstrated conclusively. ADLERand THEODOR (1928, 1929) recorded naturally occurring leishmania in P. sergenti in Baghdad, but as some leishmanias

290

AN ANALYSIS OF TIIE I,EISHMANIA SANDFLY PROBLEM.

of geckoes can also develop in sandflies, and there are no constant morphological differences between the leishmanias of geckoes and those of man, there is no certain method cf determining tbe species of leishmania found in a wild sandfly except by inoculation experiments. Flagellates from one naturally infected P. sergenti were inoculated into a man with a negati~,e resuh. THE POSSIBLE MODES OF TRANSMISSION OF ORIENTAL SORE BY SANDFLIES. Two methods of transmission are possible, by bite and by crushing. The tendency of L. tropica to adopt an anterior position and its occasional extension into the proboscis suggest transmission by bite. In a number of attempts to transmit L. tropica by the bite of P. papatasii 253 heavily infected sandflies fed on twelve men and one puppy, and only one man out of the twelve men developed oriental sores on a site on which sandflies fed. Since this volunteer lived for several months under conditions in which he could have acquired the disease naturally, it is preferable not to consider this experiment as conclusively proving transmission by bite. Even if we consider the positive case as being produced by the bite of a sandfly it would only prove that, out of a large number of heavily infected P. papatasii (kept at 10° C. to 23 ° C.), which feed on susceptible animals, only a few will transmit by bite. The invasion of the proboscis by flagellates also provides evidence for transmission by bite. Recently we have found large numbers of flagellates emerging from the tip of the proboscis of several P. papatasii (laboratory bred) infected by feeding on local lesions in mice. These sandflies died after refusing to re-feed on man. By feeding infected sandflies on inactivated blood through membranes of rabbit skin it was shown that L. tropica passed out through the proboscis of P. papatasii, but in small numbers and not constantly. That transmission by bite occurs in nature is proved by the fact that cutaneous leishmaniasis occurs in dogs on sites where infection by crushing can be safely excluded, e.g., on the ears. .4s far as is known cutaneous leishmaniasis is common in dogs only in endemic centres where P. sergenti occurs, as in Baghdad and Teheran, but it is absent or too rare to attract attention in centres where only P. papatasii carries oriental sore to man. The preparatory interval, that between the entrance of the proboscis into the skin and the entrance of blood into the food canal, is a favourable time for the inoculation of flagellates into the skin. This interval may be a half to two minutes in the case of P. papatasii. After the preparatory interval flagellates cannot enter the wound because of the strong negative pressure by which blood is forced into the food canal. Admitting that flagellates can enter the wound via the proboscis, some of them are liable to be re-drawn into the food canal with the blood or tissue juices. Transmission by bite is therefore more likely to succeed if the sandflies are interrupted during the preparatory interval than

S. ADLER.

291

if left to feed undisturbed. (In nature P. papatasii frequently bites on several sites before drawing blood). The successful experimental transmission ofL. tropica to man from naturally infected sandflies and from artificially infected laboratory bred sandflies (P. papatasii and P. sergenti) corresponds more closel 3 to transmission by crushing than to transmission by bite. It has to be admitted that in crushing the likelihood of parasites entering the wound, though very good, is not as great as in inoculation experiments. It is necessary to consider in what circumstances sandflies can be crushed in nature. If a sandfly (P. papatasii) bites man and an attempt is made to crush it, the insect usually escapes and returns to feed again. If it is disturbed several times during the act of biting and before drawing blood, the sandfly returns and does not interrupt its feed if disturbed again. Under these circumstances the sandfly can be crushed easily. This fact has been confirmed on many occasions in the laboratory in the case of P. papatasii. Naturally, crushing cannot take place when a sandfly feeds on a man who is in deep sleep, but it may take place in a case of one who is sleeping lightly or is awake. Another possible method of transmission (in the case of L. donovani) is the crushing of an infected sandfly by a person who is half awake, and the introduction of flagellates into the mouth or conjunctiva while rubbing his face. SHORTT, CRAmHEA9, SMITH and SWAMINATH (1928) have shown that hamsters are readily infected by the introduction ofL. donovani into the conjunctival sac. We think that in the case of P. papatasii transmission can occur both by bite and by the crushing of an infected sandfly. It is impossible to decide which is the commoner method in Palestine where the disease though constantly present is relatively rare. The advantage of an anterior position in the sandfly is two-fold, for it admits both transmission by bite and transmission by crushing. The flagellates of vertebrates which adopt the posterior position are transmitted by insects which def~ecate during the act of feeding, e.g., Trypanosoma lewisi by the rat flea and T. cruzi by reduviids, or they are occasionally swallowed by the vertebrate on which they feed, e.g., the rat flea in the case of T. lewisi, P. papatasiiin the case of L. ceramodactyli, and reduviids in the case of T. cruzi. (We found that rats feed readily on Rhodnius prolixus, and that a rat becomes infected after devouring a single R. prolixus infected with T. cruM). A posterior position in the case of L. tropica in P. papatasii would limit the method of transmission to crushing only, for P. papatasii very seldom defalcates during the act of feeding ; in the rare cases where it does so the f~eces dry very quickly. The presence of infective forms in the midgut in the frequent absence of flagellates in the proboscis permits transmission by crushing at a stage when transmission by bite is not yet possible. PATTON (1922) states that in Mesopotamia sandflies are frequently crushed on the skin. (This is probabl? an overstatement of the case.) PATTON (1913, 1922) and CORNWALL(1919) suggested that oriental sore is transmitted through

292

A N ANALYSIS OF T H E L E I S H M A N I A SANDFLY PROBLEM,

the crushing of infected sandflies. Because of the frequency of cutaneous leishmaniasis in dogs in Baghdad and its absence or rarity in Palestine we think that the strains of L. tropica present in Baghdad are adapted to P. sergenti, so as to be readily transmitted by bite, whereas the Palestinian strains of L. tropica are adapted to P. papatasii so as to be only occasionally transmitted by bite. We interpret the behaviour of the Palestinian strains of L. tropica in P. papatasii, namely the frequent infection in the upper parts of the cardia, eesophagus, and pharynx, and the rare infections in the proboscis, as part of a process of evolution towards the perfect mode of transmission which is only rarely attained, namely transmission by bite. Comparing the behaviour of L. tropica in P. papatasii and P. sergenti with that of T. gambiense in Glossina palpalis two interesting differences may be noted. 1. The flagellates in the midgut of G. palpalis according to Dr. H. L. DUKE are never infective at any stage of the infection. Some of the flagellates, probably the long ones, in the midgut of P. papatasii and P. sergenti are infective for man after a certain period of development. 2. L. tropica does not enter the hypopharyngeal duct or the salivary glands as the trypanosomes do. T. gambiense therefore shows a higher degree of adaptation to G. palpalis than L. tropica to P. papatasii and P. sergenti. Viewed as a whole, the leishmanias of man and dogs may be regarded not as clearly defined fixed species, but as strains which are undergoing evolution under various circumstances, for there is no single character by which one socalled single species can be constantly differentiated from another. L. tropica, for example, produces cutaneous lesions, but PATTON (1922) recorded it in the circulating blood of a case of oriental sore. Major HECGS, of Baghdad, informs us that at Baghdad, where vaccination of infants with material from oriental sore is practised among Jews, an inoculation into a single point on the leg sometimes produces lesions over the whole body, proving that L. tropica may invade the blood stream. We have found some strains of L. tropica to produce only local lesions when inoculated into the tail of mice, but the same strains invade the liver, spleen, bone marrow and circulating blood, and in addition produce lesions on mucous surfaces similar to those caused by L. brasiliensis in man when inoculated intraperitoneally into mice.* L. donovani usually invades the spleen, liver, bone marrow and blood stream in man, but it occasionally produces local lesions. The differences noted between the so-called species are differences in degree rasher than differences in kind. The leishmania of dogs in Mediterranean countries has been regarded as definitely visceral, and WEN¥ON (1926) in his book included it in L. donovani. Nevertheless PARROT and DONATIEN (1927) produce local lesions in monkeys

L. tropica inoculated intraperitoneally into white mice causes visceral leishmaniasis more frequently and very much more intensively than L. donovani.

S. ADLER.

293

by inoculation of cultures taken from dogs with visceral leishmaniasis. Working with a strain of canine visceral leishmania from Tunis, we were able to produce local lesions in the tails of mice constantly. (Sandflies, P. papatasii, became iflfected after feeding on these lesions; the flagellates adopted an anterior position.) Two strains of L. infantum from children in Naples were inoculated into a dog which developed visceral leishmaniasis. Cultures taken from the liver of this dog did not produce local lesions when inoculated into the tails of mice. In different countries the leishmanias have adapted themselves in various degrees to different vectors of the genus Phlebotomus, thus in Palestine L. tropica has adapted itself imperfectly to P. papatasii.* In Baghdad L. tropfca has, according to our view, adapted itself to P. sergenti to a higher degree, so as to be transmitted readily by bite. In this case the adaptation is so good that in some districts where this species is prevalent and P. papatasii rare hardly a human being escapes oriental sore. The Baghdad strain of L. tropica is even better adapted to P. sergenti than the Assam strain of L. donovani to P. argentipes, for in the former case oriental sore is constantly present in a large part of the population and as far as is known there are no quiescent periods during which oriental sore diminishes in Baghdad. On the evidence of the distribution of oriental sore and in the absence of experimental data, we think that many of the strains ofL. tropica of the Mediterranean basin are not well adapted to P. sergenti, for in Macmahon, where 20 per cent. of the sandfly population are P. sergenti, oriental sore is rare. The worker who examines a number of strains of L. tropica from different localities will be struck by the differences they exhibit, particularly with regard to their behaviour in sandflies and their infectivity for mice. We think that these variations help to explain the epidemiology of leishmaniasis. In the above discussion of cutaneous leishmaniasis we have made use of three assumptions. 1: That sandflies transmit oriental sore. For this assumption there is a mass of experimental evidence. 2. That there are leishmanias common to man and dog. 3. That the presence of leishmaniasis in dogs points to transmission by bite for dogs cannot crush sandflies in their ears. The relationship between human and canine leishmaniasis is one of the most urgent problems. SCIILIMMER(1874), who was probably the first to observe cutaneous leishmaniasis in dogs, considered the human and canine disease identical. Referring to oriental sore in Teheran, he writes : " Maladie end6mique de certaines contr~es de l'Orient elle @argne aussi peu la race humaine * In Bar Elias in Syria the local strain of L. tropica has probably adapted itself perfectly to P. papatasii.

@94

AN ANALYSIS OF THE LEISHMANIA SANDFLY PROBLEM.

que la race canine (chez laquelle du reste je ne l'ai vue d6velopper que sur le bout sans poils du nez)," p. 82. It is an interesting and probably not an irrelevant fact that wherever oriental sore is present in dogs the disease is common in infants under twelve months of age (Baghdad and Teheran). Dr. H. C. SINDERSON, of the Royal Hospital, Baghdad, at the author's request, made an enquiry and found the disease to be common in Baghdad in the first year of life.e Mr. C. MACHATTIE, of the Civil Veterinary Department, Iraq, informed the author that in Baghdad the disease is common in dogs between September and April, after which period it is very rare. Recently he found a single infected dog out of a large number examined in July. This seasonal distribution points to a non-canine reservoir, for between the end of April and the end of September there are not sufficient infected dogs in Baghdad to carry the infection on to other dogs either by direct contact or through an insect vector. Man is, in our opinion, the only possible reservoir of canine cutaneous leishmaniasis in Baghdad, for human beings are found infected throughout the whole year. Some authors have considered the human and canine leishmaniasis to be identical, for the inoculation of Leishman-Donovan bodies from human cases of visceral and cutaneous leishmaniasis into dogs when successful produces a condition indistinguishable from the disease as it occurs in dogs in nature. The evidence is, however, incomplete, for the inoculation of leishmaniasis from dogs into man has not yet been attempted. At presep.t it is impossible to distinguish between the human and dog parasites.+ Slight differences i~ size both in the vertebrate hosts and in culture are of no account. Size is the least useful of all characters in the differential diagnosis of Leishmania spp., a strain of human L. tropica when cultured and inoculated into the tail of mice produces in the latter Leishman-Donovan bodies two and even three times the size of those found in the human being from whom the strain was originally derived. Sandflies can feed on dogs only on those parts which are sparsely covered with hair. In the laboratory P. papatasii feeds readily on the inner part of the external ear, whereas it does not feed on the chest or back unless these parts have been shaved, The non-hairy parts, as SCHLIMMER(1874) and CHADWICK and MACHATTIE (1927) have pointed out, are the ones usually attacked by cutaneous leishmaniasis. It is interesting to apply these assumptions to visceral leishmaniasis. In India L. donOvani exflagellates in P. argentipes, multiplies and tends to adopt an anterior position. In China L. donovani behaves similarly in P. chinensis. A leishmania has been found in wild P. argentipes, but it cannot be concluded Dr. KURDIAN,of Baghdad, has seen the disease in an infant six weeks old. t MAeHATTm has infected wild P. sergenti and P. papatasii on a dog infected with cutaneous Leishmaniasis and on cultures through membranes. We have infected P. papatasii with MAeHATTIE'Sstrain by feeding the sandflies through membranes.

S. ADLER.

795

with certainty that it was L. donovani for the same criticism applies to this finding as to the finding of a leishmania in P. sergenti. T h e bulk of the evidence shows that in India P. argentipes and in China P. chinensis are the vectors of kala-azar. T h e following facts must be noted. YOUNG and HERTIG (1927), working in China, failed to produce visceral leishmaniasis in 413 hamsters exposed to the bites o f P . chfnensis and P. sergenti var. mongolensis. ( T h e sandflies were infected or potentially infected according to the authors.) HINDLE and PATTON (1927) and HINDLE (1928) also recorded negative results after feeding infected P. chinensis on hamsters. SHORTT, CRAIGHEAD and SWAMINATH (1928) recorded negative results after feeding 3,590 P. argentipes on white mice, 2,325 on Chinese hamsters, 1,247 on human volunteers. T h e total of 7,162 sandflies were infected on a case of kala-azar six days and more before the experimental feed. NAPIER (1929) reports negative results after feeding 458 P. argentipes on volunteers. T h e sandflies had previously been fed on a case of kala-azar. T h e position is rather similar to that of oriental sore and P. papatasii in Palestine. Visceral leishmaniasis of dogs is absent or so rare as to have been overlooked in India. DONOVAN (1909) examined 1,150 dogs in Madras without finding a single one infected. In 1913 the examination of 2,000 more dogs in Madras also gave a negative result. MACKIE (1914) did not find leishmania in ninety-three dogs examined in endemic centres in Assam. It must also be borne in mind that L. donovani from India has been proved to be infective for dogs. T h e absence of naturally occurring visceral leishmaniasis in dogs may be explained either on the assumption that transmission by bite is rare or that P. argentipes does not bite dogs. On the other hand, visceral leishmaniasis occurs in dogs in the Mediterranean basin. This suggests that in the Mediterranean basin visceral leishmaniasis is readily transmitted by bite. ~ MCCOMBIE YOUNG (1924) gives the following statistics of the distribution of kala-azar in Assam according to age for the year 1922 based on the n u m b e r of treated patients.

No. of Cases

Under 1 year.

1-5 years,

5-10 years,

11

1,520

3,528

10-15 years, 3,390

15-20 years.

I

2,834

20-30 years,

30-40 40-50 Over 50 years, years, years.

2,995

1,607

529

24

116"9]

9"6

2"9

0"37

b

Percentage

0"06

8.59

20.5

20.2 I

16

Total percentage up to 5 years, 8.65. Total number of cases, 17,724. Membrane experiments similar to those employed for demonstrating the exit of

L. tropica through the proboscis of P. papatasii would in our opinion give more striking results with the vector of Mediterranean kala-azar and an appropriate strain of L. infantum.

296

AN ANALYSIS OF THE LEISHMANIA SANDFLY PROBLEM.

A G E D I S T R I B U T I O N I N ASSAM OF CASES UP TO 10 YEARS.

5-10 years.

Under 1 year.

1-5 years.

11

1,520

3,528

0-217

30.04

69.74

N u m b e r of Cases . . Percentage . . . .

Total percentage up to 5 years, 30,257. Total number of cases, 5,059. NAPIER (1926) gives the f o l l o w i n g data for a village i n B e n g a l ( t r e a t m e n t centre). L

I

Percentage

..

Under 1 year. 0

years.

5-10 years.

10-15 years,

8

29

23

1-5

I

15-20 years.

20-30 years•

30-40 Over 40 years, years.

17

14

7

20-30 years.

30-40 years.

2

Total n u m b e r of cases, 1,559.

CALCUTTA O u T - P A T I E N T C L I N I C .

1-5 Under I year. years.

5-10 years,

10-15 years.

15-20 years.

Oy::rr:O (

..

Percentage

4.1

0.28

17

25.5

17•5

21"2

- -

I 9.215.5

Total number of cases, 2,106. T h e greatest n u m b e r of cases, as NAPIER r e m a r k s , are b e t w e e n the ages o f 5 a n d 15. T h e f o l l o w i n g table is b a s e d o n the figures of DA CAPUA (1926) for Italy.

U n d e r 1 year. 6-9 9-12 months, months. 12 No. of Cases

• .

26

k . _ _ ~

J

1-2 years•

3 •

•

4-6 years•

6-9 years.

98

26

15

12

24.5

6"5

3-75

I

mo__ths__[mo__?ths 94

118

t ___.y~._#

212 6.5

3-4 years,

12-18 [ 18-24

38 Per cent...

2-3 years•

23.5

29.5

k~___y___.__2

~-__-y---.--J

9"5

53

Total percentage up to 5 years, 93.25.

297

S. ADLER.

The following table is based on PERADISO'Sdata (1926) :

years.

2-3 years.

3-4 years.

4-5 years.

5-10 years.

168

694

248

116

46

46

11"8

48.74

17.42

8.15

3"23

1-6 6 months months to 1 year No. of cases

21

Percen- ] rage JJ 1.47

I-2

3.23

10-15 years.

Not stated 78

0"49

5'48

Total No. of cases 1,424. Total percentage up to 1 year 13.27. Total percentage up to 5 years 90.81. Comparing the statistics fronl Italy and India, the most striking difference is in the infection rate in children up to 1 year in both countries ; the infection rate in children u n d e r 1 year in India is only 0.06 per cent. of the total, and 0.217 per cent. of the c~tses up to 10 years of age. This suggests very strongly that in Italy transmission is by bite, for infants u n d e r 1 year of age cannot readily crush sandflies. T h e small n u m b e r of infants under 1 year infected in Assam suggests that here transmission by bite is rare. T h e only other explanations possible are that infants u n d e r 1 year are relatively i m m u n e to the Indian virus, or that the incubation period in Indian infants is more than one year. Some of the cases in Assam may be congenital ; in Italy, although congenital transmission cannot be absolutely excluded, it must be very rare indeed for, as far as is known, very few adult females are infected with visceral leishmaniasis in the Mediterranean basin. T h e view that in Italy transmission occurs by bite is f u r t h e r supported by the fact that more than 93.25 per cent. of the cases in the first ten years of life occur in children up to 5 years of age, as against 30.26 per cent. in Assam. (Unfortunately we know of no figures giving the distribution according to age for every year between one and five in India.) T h e above suggestions, namely, that transmission of visceral leishmaniasis in Italy occurs mainly b y bite, and in Assam only occasionally b y bite and usually by crushing, may be objected to on the grounds that visceral leishmaniasis is very c o m m o n in the endemic centres of Assam and relatively rare (as compared to Assam) in Italy, and that since transmission by bite is more efficient than transmission by crushing, the disease should be c o m m o n e r in Italy than in India. But it must be r e m e m b e r e d that m a n y factors are involved in the transmission of a leishmania by sandflies, e.g., infection rate in the sandfly, infection rate in the proboscis of the total n u m b e r of sandflies infected, feeding habits of various species of sandflies. T h e r e may be a low infection rate in the sandfly vector combined with a high infection rate in the proboscis of the total n u m b e r of positive sandflies. In the case of Mediterranean leishmaniasis a low infection rate in

298

AN

ANALYSIS

OF

THE

LEISHMANIA

SANDFLY

PROBLEM.

the transmitting sandfly is practically certain because of the scarcity of LeishmanDonovan bodies in the circulating blood. It is impossible to abandon the sandfly theory of leishmaniasis, for the bulk of the evidence favours it, and all other biting insects so far suggested can be safely excluded. The development of L. tropica in P. papatasii and P. serge&i, and of L. donovani in P. argentipes and P. chine&s points to transmission by bite. Numerous attempts to transmit by the bite of P. papatasii, P. chinensis and P. argentipes containing infective flagellates have failed. Attempts on a large scale with P. sergenti and Baghdad strains of L. tropica have not yet been made. We think for reasons stated above that such attempts would be most likely to succeed. Even if out of all these numerous attempts with infected sandflies one had given a positive result it would have been legitimate to criticise this result as proving only that P. argentipes and P. chinensis can occasionally transmit L. donovani by bite, and that transmission by the bite of these sandflies camzot therefore be responsible fey epidemics on a large scale. SHORTT, CRAIGHEAD and SWAMINATH (1928), commenting on their attempts to transmit by bite, make the following significant statement : “ The intensity of exposure to infection in the form of bites from infected flies is very much greater in the series of experiments described than could ever be obtained in nature within the same time period.” This applies also to the experiments of HINDLE and PATTON and of YOUNG and HERTIG with P. chinensis and of ADLER and THEODOR with P.papatasii. In seeking to account for these results the following alternatives suggest themselves. 1. Transmission under natural conditions is by bite, but the infection in the artificially infected flies was not sufficiently advanced, and the conditions obtaining in nature were not reproduced in the laboratory. (In the case of L. tropica and P. papatasii inoculations of flagellates from naturally infected sandflies into three human beings gave positive results in all three cases (1926), whereas inoculations into nineteen volunteers from nineteen artificially infected sandflies from eight to twenty-one days after the infecting feed on an experimental case of oriental sore gave positive results in six cases only.) Or 2. Transmission .of L. tropica (Palestinian strains) by the bite of P.papatasii, and of L. donovani by the bite of P. argentipes and P. chinensis occurs in nature, but it is not common, and in the case of the two latter sandflies cannot account for epidemics of kala-azar, and that other methods of transmission, such as crushing, should be considered. We therefore suggest that the following possibilities should be considered : 1. Cutaneous leishmaniasis in Palestine may be transmitted by the bite or by crushing of infected P. papatasii. 2. Cutaneous leishmaniasis in Baghdad is transmitted readily by the bite of P. smgenti. Transmission through crushing is not excluded.

S. ADLER.

~99

3. Visceral leishmaniasis in the Mediterranean is t r a n s m i t t e d b y the bite of sandflies. 4. Visceral leishnlaniasis in India is transmitted b y the crushing of infected P. argentipes, and only occasionally by bite. T h e above suggestions are based on the knowledge (very imperfect), and the experimental data available. All the possible objections to t h e m have been raised. T h e y have the merit of explaining the discrepancies in the distribution of h u m a n and canine leishmaniasis ~ and the differences in age distribution in various endemic centres, and they can be tested experimentally. I t is admitted that they are derived theoretically, and a theory which explains the facts is not necessarily correct. ( T h e facts can be explained equally w e l l b y assuming that P. argentipes n e v e r bites dogs, and the incubation period of the Indian virus is m o r e than one year, or that susceptibility to the Indian virus increases progressively up to the age of 10, and decreases in the case of the Italian virus.) Only experiments are decisive. Nevertheless, the above analysis is considered justified in the present state of the leishmania p r o b l e m , and it is felt that the subject should be discussed f r o m every possible angle. REFERENCES. ADLER, S., and THEODOR, O. (1925). The Experimental Transmission of Cutaneous Leishmaniasis to Man from Phlebotomus papatasii. Ann. Trop. Med. 3.~ Paraslt., xix (3), 365. (1926). Further Observations on the Transmission of Cutaneous Leishmaniasis to Man from Phlebotomus papatasii. Ibid. xx (2), 175. ---(1927). The Transmission ofLeishmania tropica from Artificially Infected Sandflies to Man. Ibid. xxi (2), 89. - (1927). The Behaviour of Cultures of Leishmania sp. in Phlebotomus papatasii. Ibid. xxi (2), 111. - (1928). The Exit of Leishmania tropica through the Proboscis of Phlebotomus papatasii. Nature, exxi (3043), 572. - - - - - - (1928). The Infection of Phlebotomas sergenti with Leishmania tropica. Ibid. cxxii (3067), 278. ---(1929). Attempts to Transmit Leishmania tropica by Bite. The Transmission of Leishmania tropica by Phlebotomus sergenti. Ann. Trop. Med. 6Y Parasit., xxiii (1), 1. CHADWICK, C. R., and MAeHATTIE, C. (1927). Notes on Cutaneous Leishmaniasis of Dogs in Iraq. Trans. Roy. Soc. Trop. Med. & Hyg., xx (7), 422. CORNWALL, J. W. (1922). Note on Histopathology of a Non-ulcerated Oriental Sore. Ind. ffl. Med. Res., ix (3), 545. DA CAPUA, F. (1926). La Diffusione della Leishmaniose infantile. Osservazione sulla casistica di un decennii. La pediatrica, xxxiv (9), 449. DONOVAN, C. (1913). Kala-Azar, its Distribution and Probable Modes of Infection. Ind. ffl. Med. Res., i, 177. HINDLE, E. (1928). Further Observations on Chinese Kala-Azar. Proc. Roy. Soc., B., ciii, 599. HINDLE, E., and PATTON, W. S. (1827) Transmission Experiments with Chinese KalaAzar. Proc. Roy. Soc. B., cii, 63. -

-

It has been stated that visceral leishmaniasis is present in dogs in Persia but not in man. The author recently visited Persia, and found that there are not sufficient data to justify this statement.

900

AN ANALYSIS OF THE LEISHMANIA SANDFLY PROBLEM.

Kala-Azar in Nowgong (Assam). Ind. Jl. Med. Res., i (4), 626. Some Reflections on the Kala-Azar and Oriental Sore Problems. Ind. Jl. Med. Res., ix (3), 496. (1926). Epidemiological Consideration of the Transmission of Kala-Azar. Ind. Med. Res. Memoirs, Memoir No. 4, p. 219. (1929).--Report of the Kala-Azar Research Department. Annual Report of the

MACKIE, F. P. (1914). NAPIER, L. E. (1922). -

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Calcutta School of Tropical Medicine, Institute of Hygiene and the Carmichael Hospital for Tropical Diseases, 1928, p. 66. PERADISO, F. (1926). Sulla distribuzione altimetrica del Kala-Azar infantile in provincia di Catania c sulla eth dei piccoli leishmaniotici. La Pediatria, xxxiv, (12), 664. PARROT, L., DONATIEN, H., et LESTOQUARD, F. (1927). Notes Exp6rimentales sur le Bouton de l'Orient et sur la Leishmaniose canine visc6rale. Arch. Inst. Past. d'Algdrie, v (2), 120. PATTON, W. S. (1919). Note on the 2Etiology of Oriental Sore in Mesopotamia. Bull. Soc. Path. Exot., xii (8), 500. (1913). Is Kala-Azar in Madras of Animal Origin ? Ind. Jl. Med. Res., i, 185. SCHLIMMER, J. L. (1874). Terminologie Medico-Pharmaceutique et Anthropologique.* Iraneaise-Persane, 81. Lithographie d'AIi Gouli Khan. SERGENT, ED. et ET., PARROT, L., DONATIEN, H., et B~GUET, ~/~. (1921). Transmission du Clou de Biskra par le Phl6botome (Plebotomus papatasii ScoP.). Arch. Sc., Vol. clxxiii, 1030. SHORTT, H. E., CRAIGHEAD,A. C., and SWAMINATH, C. S. (1928). A Brief Rdsum6 of Recent Kala-Azar Research with Special Reference to India. Ind. ~l. Med. Res., xvi (1), 221. SHORTT, H. E., CRAIGHEAD,A. C., SMITH, R. O. A., and SWAMINATH,C. S. (1928). Further Transmission Experiments in Kala-Azar with Phlebotomus argentipes. Ind. Jl. Med. Res., xvi (2), 263. SINTON, J. A. (1925). The R61e of Insects of the Genus Phlebotomus as Carriers of Disease with Special Reference to India. Ind. Jl. Med. Res., xii (4), 701. WENYON, C . M . (1926). Protozoology, London. Balli~re, Tindall and Cox. YOUNC, McCoMmE. (1924). Kala-Azar in Assam. London : H. K. Lewis & Co. YOUNG, C. W., and HERTIG, M. (1927). Kala-Azar Transmission Experiments with Chinese Sandflies. Soc. Exper. Biol. ~-~ Med., xxiv (9), 823. -

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* We are indebted to Dr. ELGOOD, of the British Legation, Teheran, for drawing our attention to this rare book. SCHLIMMERreasoned soundly, and suggested that mites may be both the carriers and causal agent of the disease. He deplored the absence of a microscope to control his theories.