RECENT RESEARCHES IN MALARIAL INFECTION. By W. B. BA.NNERMAN, m.d.,

Surgeon,

i.M.s.

Having lately had. an opportunity of becoming acquainted with some of the more recent literature relating to the nature of malaria, I have thought that a short resume might not be without value to medical officers in India, where reference libraries are only accessible iu the

This would appear to be we find certain emiwhen necessary nent members of the medical service still upholding the "chill" theory of Oldham ;is quite sufficient to account for all the phenomena of malaria. ( Vide Kept, of Epidemiological Soc. of London of Deer. 11th 1889, Lancet and British Medical Journal ot 21st Dec. 1889) and, the old arguments about marsh poisonreviving in port of their contention, regardless of the fact that many places far removed from marshes ar e noted for the virulence of their malarial fevers. Since the days when Klebs and Tommasi Crudelli revived the idea that malarial fevers a to due bacillus which might be

presidency the

towns.

more

sup"

they

believed

228

THE INDIAN MEDICAL GAZETTE.

had found in blood and soil * great advanThe first to throw douht on their observations was Dr. E. Marchiafava who had examined the bodies of Crudelli's patients who had died of pernicious comatose He indeed found in the blood malarial fever. of those persons filaments endowed with locomotive movements resembling spore bearing bacilli, yet they were not identified as the same forms as those found by Klebs and Crudelli in malarious earth, and Marchiafava expressly stated " that other studies were necessary before being able to pronounce on the nature and significance of these forms."f In the summer of 1882 Drs. Marchiafava and Ferraresi made a study of the blood of patients suffering from malarial and other fevers in the hospital of S. Giovanni, and "the result of these researches proved that the forms described in 1880 and supposed to be the bacillus malaria?, were only filaments arising from the inside of the red corpuscles, and which were in great " part detached owing to the heating of the blood in the process of preparation their parasitic nature being only apparent. Many such are figured in books on histology (Frey, Rauvier, etc.) and are well known to depend on the mode of preparation and chiefly on the action of heat." | Laveran in the meantime (1881-82) communicated to the Paris Academy of Medicine the results of his observations in Algeria (Lancet, November 1881, Comptes. Rendus, 1882), subsequently extending these in a large volume published in 1884 (Traitd des Fievres Palustres, Paris, 1884). He describes the following forms which he found in the blood of 180 patients out of a total of 192 examined by him; the 12 cases giving negative results having already been treated with quinine. He describes three principal forms, viz. : Crescentic motionless bodies pointed at the 1. ends with delicate outline and transparent body, colourless except for a blackish spot in the middle due to pigment granules. A fine line joining the extremities of a crescent was

they ces

have been made.

?

sometimes

seen.

Flagellate bodies. These were transparent spherules of the mean diameter of a red blood corpuscle containing pigment granules 2.

which when at rest were arranged in a circle, but often shewed rapid movements and lost On the borders of their regular arrangements. the spherules fine filaments?3 to 4 times the length of a red corpuscle?could often be perWhere at rest they ceived in rapid motion. were invisible. seen at times to bewere They come detached and to move about among the

corpuscles. *

Op 1 On the nature t Op. 2. p 306. X Op. 1. p. 77.

of Malaria.

[Aug.

1890.

Pigmented spherical bodies transparent finely granular, with pigment granules disposed irregularly at the periphery, or collected 3.

and

and of a diameter of *008 to *010 have no nuclei nor do they stain with carmine, which differentiates them from

in the

centre ;

m.m.

They

leucocytes containing pigment.

He also noted (a) melaniferous leucocytes, (b) red blood corpuscles vacuated in one or more spots containing pigment granules, and (c) free

pigment grains.

These various forms he found only before and In post-mortem exaan attack of fever. minations he found large numbers of pigment granules in the blood, especially of the liver and spleen, but in some cases also in the marrow and brain. " Laveran believes that these pigmented bodies represent different stages of an elementary parasite which he is unable to pronounce to be animal or vegetable, which exists in an encysted condition and in its perfect form becomes free " * as a moveable filament Richard of Philipoille, Algeria, confirmed these observations (Sur le Parasite de la malaria, Comptes. Rendus 1882), but maintained that the spherical pigmented bodies are developed inside the red corpuscles and that only when mature do they issue from them, and become free in the blood sometimes developing filaments as described by Laveran. These pigmented bodies had already in part been described by Frerich and Kelsch, but Laveran has the credit of having first called attention to their probable parasitic nature, and Richard of having demonstrated their existence inside the red corpuscles. In the autumn of 1883 Professor Marchiafava and Dr. Celli, of Rome, began anew the study of malarial blood, using the most recent methods of staining and

during

cultivation.

As the result of these researches carried on for they note, that the most constant appearance in malarial blood is the presence in the red corpuscles and rarely in the plasma of actively moving amoeboid bodies. In 120 cases of recent malarial infection exam-; ined by them these bodies were never absent. They consist of little masses of homogeneous protaplasm varying in size from ^ to rather more than the size of a red blood corpuscle. They are endowed with active amoeboid movements, and constantly change their shape, sending out prolongations which are occasionally seen to

several years,

ramify.

When they

cease to move

they become

rounded and a dark spot appears in the centre which gradually becomes more distinct as it decreases in size, and finally assumes the colour This appearance of the containing corpuscle. is caused by becoming bi-concave and

the"body *

Op. 1,

p. 65.

Aug.

BANNERMAN ON MALARIA.

1890.]

permitting the colour ot tlie blood corpuscle The body then expands be seen through it. and contracts for a longer or shorter time before

so

to

finally becoming quiescent.

These bodies exist in the red corpuscles, not, Laverau maintained, adherent to the outside, for their pseudopodia never pass beyond the bounding wall, and they may be seen swimming freely in the protaplasm of the corpuscle, disappearing and reappearing as they rise and sink in it, and turning over and over. Sometimes the bodies appear outside the red corpuscles as though entering or leaving them, but in those cases their form is always rounded and immobile. In dry preparations treated with methyl blue the bodies are distinctly stained and apand uniformly coloured pear either as rounded as or oftener rings in which is seeu globules the substance of the red corpuscle or a clear circumscribed space. Ou double staining the dry blood with alcoholic solution of saffraiiin and methyl blue the bodies are coloured blue while the blood corpuscles appear rose-red. Iu certain phases of movement and when immobile tliev present two parts, exterior and interior. The exterior, thicker and very brilliant, emits the pseudopodia and stains darker than the interior. Tlie central part is less brilliant, often finely granular and is thin and clear enough to allow the protoplasm of the red eorpuscle to appear through it as a clearly tieIt is not easy fined faintly coloured nucleus. to find these bodies in blood examined cold, but they may be well studied when the blood is kept at a temperature of 103? to 109? Far. In the corpuscles may often be seen bacilluslike bodies and in the capillaries coloured bodies of various shapes which are simply the organisms seen on edge or arrested in some phase of movement. These non-pigmeuted hyaline forms may be the only indication of the malarial poison, or they may occur alon^ with the pigmented bodies of Lave ran, the latter being apparently the more mature form, and occurring iu chronic cases. Professor Camille Golgi,* of Pavia, concurs iu this view; regarding the pigmented bodies as characteristic of advanced malarious infection, and iu a later paper,f Marchiafava and Celli note that the pigmented forms greatly preponderate in tertian and quartan fevers of: chronic type. Generally the red corpuscles containing the bodies appear normal and elastic, but sometimes they are sniiiller, as

229

who regarded the pigment as an integral part of the parasite, and not as a mere derivative of the hoemoglobin of the invaded corpuscle as has been proved by Marchiafava and Celli,* who in the bodies granules of the colour of saw hoemoglobin which subsequently became black and were converted into melanin. The bodies sometimes divide forming a rosetteshaped mass with the pigment gathered in the centre. This no doubt represents the mode of multiplication of the organism, as rosettes are seen to split up, setting free a new generation of young cells which scatter through the plasma. This may also take place in the unpigmeuted ;

forms.

who has made a special study of these believes that they represent the mature condition of the pigmented bodies, and he also maintains that some, if not all of the latter, are derived from unpigmented forms. The cases he studied were chiefly severe quartan fevers, but included some quotidian, tertiau and irregular types. From observation of those he formulated the following laws "I. Gradual development of the pigmented bodies till the substance of the red corpuscle completely disappears. This takes place during the two days of apyrexy, and lasts till 6 to 10 hours before the new attack. "2. Successive transformation of the pigmented bodies which have replaced the red corpuscles (having perhaps a transparent envelope of colourless corpuscle stroma still clinging round them), the pigment scattered abroad at first gradually collecting in the centre, while at the periphery a process of segmentation is noted as going on. "3. Rather rapid disappearance of the segmented bodies during the febrile paroxysm, so that no trace of them is to be found at the end of the period of defervescence.f" He also noted that numbers of pigment granules are to be found in the leucocytes duriug and after the height of the fever, which is what one would expect when it is remembered that it is then that the granules are set free by the segmentation and subsequent scattering of the bodies. Golgi believes that the bodies after segmentation and dispersion are retained in the spleen or other internal organ, to reappear before the next attack as colourless forms, and he agrees with Marchiafava aud Celli in thinking that" they represent a new generation of paracrenated and dark yellow. Sometimes, though sitic elements." Marchiafava and Celli in their not crenated, they are smaller and have a distinct most recent memoir! note that Grolgi's bodies are dark outline; often the bodies take up granules to be found before single and double tertians of reddish or black colour, and, still shewing and quotidians, as well as in quartan fevers. amoeboid movements, assume various shapes The segmentation usually takes place when the and forms. Ou ceasing to move they become red corpuscles have been nearly or altogether round, and then appear as described by Laverau, *

Op. 3,

p. 155.

t Op. 4.

Grolgi,

dividing forms,

?

* Op. 1. f Op. 3,

On the p. 163.

origin of Melanvemed I Op. 4. 30

THE INDIAN MEDICAL GAZETTE.

230

[Aug.

1890.

destroyed by the parasite, but in pernicious fevers Army of India, Pt. Ill, 1887) : Fenton Evans* (" B. M. Jour.," Apl. 1888); Prof. early division (division precoce) takes place I.M.S. before the red corpuscles are nearly destroyed. V. Jakach, Prague (" B. M. J.," 29,* March exists

and a wonderful unanimity of division is by a process of 1890) in their descriptions when compared witli those which inside new body hyaof Laveran, Richard, and Marchiafava and line forms arise. Celli. The relation of the various forms to the We have seen above how the bodies derive with the different of the from the blood cor- paroxysm and their connectiou haemoglobin pigment of malaria has not yet been fully worked types cause their death ; but. the and corpuspuscles, cles often die without this extraction of pig- out, but the following has beeu ascertained. The amoeboid and pigmented bodies occur ment, for they may be seen shrunken, crenated, in chronic aud acute cases, but are more both of a dark yellow colour, .and containing unpigMarcharacteristic of the latter. with especially the elements. mented Along hyaline bodies are sometimes found a variable number chiafava and Celli note that iu acute cases, and of little, round, highly pigmented bodies which the intermittents of summer and autumn, the These are only distinctly unpigmented forms occur, while iu those of winlook like micrococci. ter aud spring (probably old cases re-excited by seen in coloured preparations ; they may perbe the of the hyaline bodies. exposure to cold) the pigmeuted bodies were the early stage haps The Italian observers also found Laveran's most frequent. Golgif was the first to note the relation of the segmented forms to the parcrescentic forms, but chiefly in chronic cases. The flagellate organisms were noted only in oxysm, and he traces fully their development rare instances, on one occasion contained inside duriug the period between the attacks from a body to one that has absorbed the suba red blood corpuscle, but, usually free in the small ot the red corpuscle, and the subsequent stance never were more than two or plasma. There In size they vary from a half division of the parent form and dispersion of the three on a slide. to nearly the diameter of a blood corpuscle ; they young generation at the onset of the fever. Councilman, too, notes the occurrence of this are round, ovoid or pear-shaped, with finely granular protoplasm, and contain a central collec- form before the paroxysm and its disappearance It always occurs along with the tion of pigment grains often shewing Brownian afterwards. amoeboid bodies, in being, it is believed, their mavaried number movement. The flagella from The crescents are found in malarial ture form. one to four; they were long, slender and delicate, often in great numbers, in which cases measuring three to four times the breadth of the cachexia uo amoeboid forms occur; they also occur in chrobecome would detachbody. Rarely the flagella under treatment for some time. ed from the body aud move away as free swim- nic cases or those are mostly seen in chroorganisms Flagellate ming cilia, as noted by Laveran, who, therefore, and Councilman states that they are cases, nic the essential was that the cilium elethought found in blood taken direct from the spleen. ment, and that the body represented a cyst in best " must' be common if not says they CarterJ which it was developed. since they were repeatedly seen in To summarise the results of Marchiafava and invariable, ot seven examples under review, and Celli's researches in their own words,* the prin- six out characteristic forms are :? probably only* just missed iu the remaining ?

Another mode

vacuolation of the

cipal " (a) Non-pigmented intra-corpuscular

amoe-

cases."

The effect of

quinine on the organisms is very according to most observers, when (b) Pigmented intra-corpuscular amoeboid forms. quinine is given, the hyaline and pigmented decrease rapidly in number and become " (c) Free pigmented forms, with or without bodies to affect Arsenic does not boid forms.

great, for,

"

mobile filaments. "(d) Semilunar pigmented forms. " (e) Pigmented forms with uudulatingoutline. "(/) Pi gmented forms in various stages of segmentation up to the formation of young bodies. " (g) Non-pigmented forms in process of segmentation (cerebral capillaries)." These various forms have also been seen by Councilman of Baltimore?Abbot (

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