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William H. (William Heiskell) Deaderick.

A practical study of malaria online

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After drying again the film is stained by one of the usual
methods. While the outlines of the red cells are still visible,
the cells are transparent and parasites may be detected, though
lying under several cells. The advantage of this method is
that a much larger volume of blood may be examined in a
shorter space of time than is the case with the thin film.

Flagella are much more easily demonstrated in the gametes
of the estivo-autumnal than of the tertian and quartan para-
sites. The crescent becomes oval and then spheric before
exflagellation is observed. To encourage this process the
method of Stephens and Christophers 118 is most practical. A
number of rather thick drops of blood are placed upon a series
of slides. The slides are then inverted, with the hanging drops
over holes cut in blotting paper, moistened with water, and
spread on a pane of glass. A series of moist chambers is thus
made. A slide is removed at intervals of five minutes, the
blood spread in the usual manner and stained. Exflagellation
is also observed in preparations of fresh blood. The warm
stage, breathing upon the specimen, and the addition of a little
water are recommended to hasten the process.

Sources of Error. — In the examination of blood for mala-
rial parasites there are several objects which may mislead. Pit-
falls are probably more common in fresh blood than in stained
films.



DIAGNOSIS 269

Vacuoles and retractions of hemoglobin in red cells of fresh
preparations are delusive and not infrequently mistaken for
the young hyaline forms of the parasite. They are most com-
mon in the center of the cell, while parasites are found in any
portion. Vacuoles are highly refractive, having well-defined,
clear-cut edges ; the margins of the parasites are dim and fade
gradually into the substance of the red cells. The vacuoles
may show slight changes of form, but do not possess true
ameboid motion nor pigment. While the vacuoles are per-
fectly clear, the parasites show a slight opalescence. In stained
specimens areas which do not take the stain may deceive.
These areas may be of circular form in the center of the cell,
or of ring form surrounding the center, or may be oval, horse-
shoe shaped, crucial or irregular. When present they are apt
to be abundant in some portions of the film and entirely absent
elsewhere.

Crenations of red cells may present a hyaline appearance
somewhat resembling an ameboid parasite. Their nature may
be determined by changing the focus.

Bent or buckled corpuscles occasionally resemble crescents.
The absence of pigment and the size of corpuscle should, how-
ever, enable a distinction. Overlapping of the corpuscles may
produce a ring or crescent appearance which deceives the be-
ginner.

The object in stained spreads which proves most deceiving
to the inexperienced is probably the blood platelet. These cor-
puscles may lie upon or within the red cells, in the center,
near the periphery, or only partially enclosed by them. They
are from one-seventh to one-half the size of a red blood-cell,
and are round, oval, or elongated in shape. They are often
of mulberrry shape and reticular structure, and, with the
Romanowsky class of stains, approach more nearly purple or
lilac than the characteristic blue of the parasites. The margin
is surrounded by a pale or unstained area resembling a halo.
There is, of course, an absence of pigment and chromatin.
Occurring in groups, as it frequently does, it has not rarely
been mistaken for a sporulating body, and isolated for a free



270 THE STUDY OF MALARIA

spore. Bodies resembling free spores should, however, be
disregarded for diagnostic purposes.

The nuclei of nucleated red corpuscles may be mistaken for
parasites, but this should rarely occur if the morphology and
staining reactions of both bodies is borne in mind.

Cabot 342 and others have found in the blood of patients
afflicted with pernicious anemia, leukemia, and lead poisoning
ring-shaped bodies occurring within the red cells and not unlike
malarial parasites. Their origin or significance is not known,
but they are thought to represent nuclear remains.

Pigmented leukocytes have been mistaken for parasites, but
the ameboid motion of the former in fresh specimens and the
staining reactions in dried films should prevent confusion.

Hemokonia, or blood-dust, may be confused with free spores.
They are small, highly refractive, micrococcus-like bodies aver-
aging one-half micron in diameter and possessed of very ani-
mated motion. . As stated, free spores should not be sought for
diagnosis, and bodies resembling them should be ignored.

Extraneous dirt, leukocyte granulations, and stain precipi-
tates must be carefully distinguished from pigment.

The amateur in examinations of malarial blood is apt to be-
come decidedly discouraged, even when he has satisfactorily
mastered the technic in the laboratory. Most students gain the
impression that all that is necessary to find the parasites is to
locate a malarial subject with any form of the disease and
obtain the necessary blood at any stage of parasitic develop-
ment, to stain it properly, and to inspect it under a high-power
lens. Usually this is what he has been taught by text-books
and by teachers, and when he fails to detect the characteristic
organisms in undoubted cases of malaria he is disgusted. The
results of such teaching throw discredit upon a discovery whose
practical importance is unsurpassed in modern medicine.

To estimate the value of a report on the result of micro-
scopic examination of the blood for malarial parasites it is
always desirable to know something of the experience of the
examiner. In addition to competence and proper technic there
are several factors which influence the result of the examina-
tion for parasites. The most important of these are: (a) the



DIAGNOSIS 271

previous administration of quinine; (b) the stage of develop-
ment of the organisms; (c) the stage of the disease; (d) the
type of infection; (<?) race; (/) locality, and (g) individual
circumstances.

(a) The previous administration of quinine, even in small
quantities, renders it almost useless to examine the blood with
the expectation of finding parasites. Even where the quantity
of the drug - is insufficient to have any effect on the symptoms,
it will ordinarily cause a disappearance of the parasites from
the peripheral circulation. The half-poisoned parasites which
persist in some instances are frequently unrecognizable with
reference to type.

(b) The quartan parasite is nearly evenly distributed in all
its phases, from the youngest form to the sporulating body,
throughout the superficial and deep circulation. Hence, when
dealing with this type it makes little difference at what period
the blood is examined. But with the estivo-autumnal organism
it is only the early stages, the small rings, that are observed
with any degree of frequency in the peripheral blood, and if
the examination is made when the parasite has reached a later
stage of development it will probably be missed. Instead of
resembling the quartan parasite in habit of distribution it seems
to imitate its more distant relative, the Leishman-Donovan
parasite. Later phases of the simple tertian hematozoon are
less commonly found in examinations of the peripheral blood
than are those of the quartan, but are much more frequently
observed than those of the estivo-autumnal. Sporulating
bodies of the quartan type are not uncommon in the cutaneous
blood, while those of the tertian are much less common and
those of the estivo-autumnal extremely uncommon.

The frequency with which crescents are detected varies with-
in the broadest confines. In the experience of some they are
rare, while other observers note them frequently in estivo-
autumnal infections. Tertian gametes are not rarely observed
in the blood of the superficial circulation, while quartan gametes
are scarcely found.

(c) In acute untreated malaria the parasite can be detected
at some stage of its growth in almost 100 per cent, of cases.



272 THE STUDY OF MALARIA

If not found at the first examination, as frequently occurs,
subsequent searches are usually successful. On the contrary,
in chronic malaria the parasites are far from constant during
the stage of latency, and prolonged search may fail to reveal
them during the relapse. Parasites are often absent from the
peripheral blood of malarial cachectics. In the paramalarial
syndrome, hemoglobinuric fever, the parasites, if present before
onset, afterward disappear in the majority of cases.

(d) The behavior of the different kinds of parasite in their
various stages has been referred to. As a rule, the quartan
parasite is most certainly found on first examination, the estivo-
autumnal least so, on account of its habit of resorting to the
deep circulation when approaching maturity. It is very unfor-
tunate for rapid diagnosis that the estivo-autumnal parasites
are less readily detected than those of the benign infections,
but, fortunately, are usually easily found in pernicious cases of
estivo-autumnal infection.

(e) That malarial parasites are found less frequently and
in smaller numbers in the superficial circulation of negroes with
malaria the writer is convinced, though the difference is slight.
This opinion is confirmed in part by the observations of Kulz, 247
who found malarial parasites much less frequently in his negro
malarial patients than in white.

(/) Along the Northern borders of malarial distribution the
parasites are probably more readily detected. This may be
accounted for partially by the greater relative frequency of
simple tertian infections. Whether the more northern negro
shows the same scanty distribution of parasites in the peripheral
blood as manifested by his southern brother the writer has no
means of determining. It is surprising with what frequency
crescents are found in higher latitudes in the blood of patients
moving from highly malarial localities where crescents are not
so frequently observed. Whether this is a conservative measure
related to the relative rarity of anopheline mosquitoes cannot
be stated positively, but it is known that the life histories of
animals are, in some instances, peculiarly interdependent, espe-
cially in the case of parasite and host.

(g) Why it is that in certain unquestionable cases of malaria



DIAGNOSIS



2 73



which have received no quinine and in which every condition
seems favorable to finding the parasites prolonged and repeated
examination shows none is not known, but such cases are some-
times encountered.

As before said, where the specific can be withheld and re-
peated examinations made by a competent microscopist if not
found at the first examination, the parasite may be found in
almost ioo per cent, of cases of malaria. The question, which
is of the utmost practical importance to the physician, arises :
In what proportion of cases is the parasite to be found at a
single examination? On this depends in great measure the
practical value of Laveran's discovery, for in not a few cases
in general practice for reasons of convenience the examination
cannot be repeated, in others in which the diagnosis seems
more or less clear urgent symptoms are demanding the specific.
The two factors which more than the others influence the result
are whether or not the patient has received quinine and the
phase of parasitic development attained when the blood is with-
drawn for the examination. Neither of these factors is always
within the control of the physician who desires to make a diag-
nosis upon examination of the blood taken when the patient
first comes under his observation. Since a very large proportion
of the malaria of the land is treated by country doctors, the
practical value of a diagnostic test is largely in proportion as
it is applicable by them.

With reference to the number of cases in which the parasite
can be found at the first examination the writer will state his
experience. From a record kept of the number of malarial
cases which had taken quinine in some form before coming
under observation it was learned that this reached something-
over 50 per cent, of the total number of cases treated. The
diagnosis in these cases was obviously based upon the clinical
history and the therapeutic test, since the search for parasites
in the blood of persons having received quinine is so discourag-
ing that this has not been done in routine work, but only in
special cases. Allowing for errors in diagnosis might reduce
this number to 50 per cent. A specimen of blood was always
taken from malarial patients who had not recently received

18



274 THE STUDY OF MALARIA

quinine when they came under observation for the first time,
irrespective of the stage of the access. The blood from frank
cases only has been included, no cases of atypic or latent mala-
ria or of cachexia figuring in the result. Parasites were found
in approximately two-thirds of the cases and the examination
was negative in about one-third. No difference as to clinic
course, severity, or the efficacy of quinine could be detected
between the cases in which parasites were found and those in
which none were observed. From this experience may be in-
ferred that in localities in which half of the malarial subjects
take quinine in some form before consulting a physician the
parasite can be detected at a single examination of the periphe-
ral blood taken at random with respect to the stage of parasitic
growth in approximately one-third of the cases only. The
prevalence of self -medication with quinine products depends
largely upon local custom and upon the energy of the patent
medicine industry.

The experience of the writer being somewhat at variance
with the conventional text-book teaching, he feels it incumbent
upon him to cite the experience of others in this matter of the
most vital interest.

Craig 70 says, "Often if the blood be examined but once none
at all will be found."

Fornario 343 observes that the parasites are missed with ex-
treme frequency, and Soliani, 147 in an analysis of 612 cases
under his care, says that in many cases the first examination
was negative.

McElroy 344 says, "I have been struck with the frequency with
which I have been unable to find parasites in cases where I
am strongly impressed with the malarial nature from the
clinical history."

Plehn 345 states that the parasites are frequently lacking in
the malaria of natives, or at least they are not found in the
peripheral blood, where the temperature curve is typic and
pigmented leukocytes indicate malaria.

The experience of Ewing 27 at Camp Wikoff is interesting.
"In the 605 cases of malaria the plasmodia were found in the
blood in 335 cases, while in 270 cases the diagnosis was based



DIAGNOSIS 275

upon the clinical history and the discovery in the blood of evi-
dences of malarial infection. The evidences of malarial infec-
tion in the blood consisted ( 1 ) usually in the presence of intra-
cellular bodies so much affected by quinine that their exact
type could not be positively determined; or (2) in the presence
of typic pigmented leukocytes; or (3) in chronic cases of dis-
tinct clinical character in the presence of marked anemia."

Leonard Rogers, 86 than whom there is no more competent
observer, says: "As long ago as 1896 I showed from an ex-
amination of 100 cases of consecutive malarial fever before the
administration of quinine that in only one-third of them could
the malarial parasite be found by means of a prolonged search
of a single blood film."

Delaney's 346 experience is even more disheartening. He con-
cludes : "I think that I shall be supported by most competent
observers in India that this ( 1 7 per cent. ) about represents the
percentage of success in finding malarial parasites in the mala-
rial fevers of India at a single examination, and on this point
both text-books and writers on the subject are, I consider, very
misleading."

Such quotations from practical workers and keen observers
could be multiplied, but could add no further weight to the
authority of those cited.

The above statements are not meant to cast the slightest
doubt upon the etiologic role of the parasite of malaria, or its
presence in every case of acute untreated malaria, or its great
diagnostic value under certain circumstances, but are intended
to demonstrate that the detection of the parasite is subject to
several conditions. In probably no other disease, associated
with a pathognomonic sign which can be elicited in almost 100
per cent, of cases, is its detection so dependent upon conditions
beyond the control of the physician.

What is the value of a positive result of examination of the
blood for malarial organisms? This parasite is thoroughly
established as the sole cause of malaria, and its pathogenic
reputation has never been marred by rumors of etiologic asso-
ciation with other diseases, but is the parasite, when present,



276 THE STUDY OF MALARIA

responsible for the symptoms which instigate the blood ex-
amination ?

In localities where a considerable per cent, of the inhabitants
carry malarial germs in their blood without showing malarial
symptoms it is manifestly possible that parasites might be
found in the blood of such inhabitants during the course of
other ailments. And such is actually the case in certain regions
with a very high endemic index, to such an extent, indeed, that
the widely experienced Albert Plehn," in Cameroon, declared
that the presence or absence of malarial parasites in the blood
of the West African coast negro is of no diganostic value.

In cases of coma in which malarial parasites are detected
and which give a history of exposure to violent heat or of the
abuse of alcohol, it is not infrequently difficult to determine the
part played by the parasite. In cases of coma accompanied by
malarial parasites in the blood and albumin and casts in the
urine the diagnosis may be obscure. Fever occurring during
the puerperium in subjects of former malaria will make the
thoughtful physician uneasy for a short while at least, even if
parasites are found on blood examination.

These are mainly problems, however, which are involved in
other fields of diagnosis and serve to impress the fact that com-
plications must be excluded or, if found, weighed. While
these contingencies should not be lost sight of, in the immense
majority of cases in this country active forms of the malarial
parasite detected in the blood are responsible for the symptoms
which bring the patient under the care of the physician or
which prompt the physician to make the examination.

It will be noted that the word active is emphasized. What,
then, is the value to be attached to the discovery of gametes
alone ?

Formerly it was believed that the sole function of these pecu-
liar bodies was the perpetuation of the species through the
mosquito cycle. Under this limited view the detection of
gametes alone was on a diagnostic, par with anemia and spleno-
megaly, sequelae of malaria, and not necessarily proof of exist-
ing malaria, even latent. Since it has become known, however,
that under certain not well understood conditions the macro-



DIAGNOSIS 277

gametes can immediately, by the process of parthenogenesis,
give rise to pyrogenic parasites without undergoing the mos-
quito cycle, our views must be modified, and these forms must
be regarded clinically as the parasites of latent malaria. Rela-
tive to active malaria, they may be looked upon as evidences
of past and potential, but not necessarily of present, active
malaria.

In regard to the number of parasites in a given film of blood
the following classification applies to estivo-autumnal infec-
tions :

Abundant when there is an average of two or more parasites
to each field of the microscope ; they are detected immediately.

Moderately numerous when present in only one of several
fields ; found after a few minutes' search.

Scanty when only a few parasites are detected in the entire
film, as commonly prepared, aften ten to thirty minutes' search.

While there are many cases of estivo-autumnal infection in
which the parasites are scanty, large numbers of estivo-
autumnal parasites are occasionally observed in the peripheral
blood, especially of pernicious cases. As many as 75 per cent,
of the red cells have been found infested in several cases re-
ported, and Rogers 44 mentions a rapidly fatal case in which
the blood showed more parasites than erythrocytes.

What is the diagnostic value of a negative result?

The writer can by no means agree with those who maintain
that such a result positively excludes a diagnosis of malaria.
The failure to find parasites in the blood of a single film taken
without reference to the period of the paroxysm, while of some
value, is not conclusive, and if the patient has recently received
quinine is absolutely worthless. On the other hand, if the blood
of a patient who has not recently taken quinine be examined
repeatedly by a competent person with the result that no para-
sites are found, it is very strong evidence against malaria.
The diagnostic value, then, of a negative finding depends upon
the presence or absence of the conditions which have been
enumerated, the chief of which is the administration of quinine.

When the examination of the peripheral blood is negative
puncture of the spleen has been advised, as the parasites in all



278 THE STUDY OF MALARIA

stages are easily detected in the blood of this organ. This pro-
cedure, however, is attended with some degree of danger, espe-
cially of hemorrhage, and should be resorted to only in cases
where an immediate diagnosis is imperative. It has been esti-
mated that the mortality of aspiration of the spleen is 1^2 per
cent. 158 Many fatalities have resulted in India recently from
this method of obtaining blood for the study of the Leishmann-
Donovan parasites. 44 When decided upon the following pre-
cautions should be observed : An aspirating syringe or even
an ordinary hypodermic syringe may be employed. A flexible
connection between needle and nipple, such as comes with the
regular antitoxin syringe, is valuable to prevent laceration of
the capsule of the spleen in the event of sudden respiratory
movements. Both the syringe and the site of injection should
be rendered sterile. Cutaneous sensation may be deadened with
cocaine or with ethyl chloride. The patient should be in-
structed to hold the breath on deep inspiration, and the spleen
should be steadied against the ribs and diaphragm. The needle
should be inserted deeply and when the syringe is half filled
should be partially withdrawn, then filled, to obtain the blood
from two points. The operation should be performed quickly,
that the patient may not have to breathe during the process,
as the danger of laceration is thereby increased. Afterward
the cutaneous puncture should be sealed with collodion, the
patient kept at rest in the recumbent position for twenty-four
hours, and cold applications placed over the region of the
spleen. A dose of calcium chloride administered half an hour
before the procedure might lessen the tendency to hemorrhage.

Upon failure to discover parasites in the blood there are two
other blood signs which must be considered. These are the
presence of pigment and a relative increase in the large mono-
nuclear leukocytes. These signs are termed subsidiary evi-
dences of malaria, because, being secondary in diagnostic im-
portance to the parasites, they are generally called upon only
in the absence of the latter.

Melanin is pathognomonic of malaria, and its presence is
not contingent upon the stage of development of the parasites
■or upon the previous administration of quinine. Theoretically,



DIAGNOSIS 279

therefore, it should be of the greatest significance in the diag-
nosis of malaria. There are, however, certain circumstances
which detract from its practical value. Free pigment, or that
lying upon the red blood-cells, should be ignored in the diag-
nosis, as it cannot be distinguished from adventitious detritus.
Within the large mononuclear leukocytes, the leukocytes in
which it is most frequently found, it must be carefully distin-
guished from the minute pigment-like granulations which may
occur normally in these cells to the number of one, two, or
three to each cell. This requires a considerable degree of
experience and deceived a no less accurate observer than Vin-
cent. 347 Coarse granules of pigment are much more readily
recognized, especially in fresh blood. In stained films precipi-



Online LibraryWilliam H. (William Heiskell) DeaderickA practical study of malaria → online text (page 23 of 36)