Spain and was shown cases of pellagra by Casal, described the
disease in 1755 and gave full credit to Casal for the recognition
of the disease. The name of the disease was given it by Frapolli,
in 1771, the derivation being from pelle—skin, and agra—rough.
The disease had then existed in Italy for a considerable time.
Casal called the disease mal de la rosa.
In 1810, Marzari insisted that the two diseases, pellagra and
Alpine scurvy, which had a few years previously been recognized as
identical, were caused by the consumption of maize and from this
time on the maize theory as to etiology has been supported in Italy.
Later on (1872 to 1909) Lombroso elaborated the maize theory of
etiology and so strongly presented this view that it is impossible
for us lightly to set aside the arguments of this great physician.
While the zeists, as the advocates of the maize etiology are
termed, insist that pellagra made its appearance in Europe
following the introduction of Indian corn, after the voyages of
Columbus, there does not seem to be any evidence that pellagra ever
existed among the North American Indians. In 1905 Sambon insisted
that pellagra was a protozoal disease and in 1910 claimed that it
was probably transmitted by a midge, _Simulium reptans_.
About 1907 pellagra was found to be an important disease of the
Southern States of the United States and since that time the number
of cases has steadily increased so that it is now estimated that
there have been approximately 200,000 cases in the United States.
It is generally conceded that isolated cases of pellagra had
occurred in the United States prior to 1907, but they generally
were diagnosed differently.
=Geographical Distribution.=—In Europe it is most prevalent in
Italy, Balkan States, Greece, Turkey, Spain and Portugal. In
Roumania there were about 100,000 cases in 1906. The disease has
decreased in incidence and virulence in Italy, there having been in
1910 only 33,869 cases, as against 104,607 cases in 1881.
The disease was first recognized in Egypt by Sandwith in 1893 and
is now known to be widespread in Lower Egypt. It is rare in Upper
Egypt where they live on millet instead of maize. It exists in
Algiers.
It has been reported from India and the Straits Settlements and
prevails extensively in the West Indian Islands as well as in
Mexico and Central America.
The disease in the Southern States of the United States is of a
more fatal type than elsewhere, the average mortality having been
39.10%. The death rate in the United States has fallen, thus the
rate in Mississippi for the years 1914 to 1916 was only ten per
cent.
At present the Italian mortality is only about 3% although formerly
it was much higher.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—Like other diseases of unknown etiology the views in
this connection are innumerable.
_Zeists and Anti-zeists._—It is customary to divide the adherents
of the different views as to the cause of the disease into two
groups, the zeists, who advocate a connection between maize or
Indian corn (_Zea Mays_) and the disease, and the anti-zeists, who
claim that corn has nothing to do with pellagra.
_Food Deficiency._—Before taking up the better known considerations
noted above it may be stated that many now believe that pellagra,
along with beriberi and scurvy, belongs to the group of “food
deficiency” diseases. Just as beriberi is caused by the absence of a
neuritis-preventing substance or vitamine in the dietary, so is the
symptom-complex of pellagra brought about by the absence from the
dietary of some vitamine or vitamines essential to proper metabolism.
There are various ideas as to the factor which eliminates the
pellagra-preventing vitamines.
Some claim that in the process of milling maize the
vitamine-containing outer portion (bran) has been taken off just as
with beriberi-producing white rice, from which the pericarp with
its neuritis-preventing vitamine has been more or less completely
removed.
From analyses of milled maize and millings Funk has recently
suggested that pellagra in different countries is in relation
to the degree of milling. Just as with rice and maize so does
excessive milling of wheat get rid of vitamines, therefore, bread
made from highly milled flour is dietetically deficient.
Again, as brought out by Voegtlin, alkalis tend to destroy any
remaining vitamines in such bread. The practice of using sodium
bicarbonate in preparation of bread is a further factor in the food
deficiency problem. With the use of baking powder or buttermilk
the alkaline carbonate of soda is neutralized so that there is no
destructive effect on vitamine content.
The vitamine deficiency of highly milled flour and highly milled
corn meal runs parallel with the phosphorus pentoxide content of
such products. Whole wheat shows about 1.1% P_{2}O_{5}, while
highly milled flour contains only about 0.1%. Whole corn has about
0.76% P_{2}O_{5}, while milled corn meal has only about 0.3%.
Highly milled rice has under 0.4% P_{2}O_{5}.
Others think that as the result of bacterial or mould diseases of
the corn grain these important vitamines are destroyed. Then too,
as with rice and beriberi, the prevailing idea is that while there
is a striking association between a maize dietary deficient in the
pellagra-preventing vitamine and the occurrence of pellagra, yet this
deficiency may be supplied by other foods.
Beriberi seems rather definitely to be associated with a deficiency
in the anti-neuritis vitamine, which is probably the same as water
soluble B., and in pellagra-producing diets a similar deficiency
may be noted. More striking however is the deficiency in fat
soluble A in such diets. This vitamine is abundant in butter fat
and egg yolk, articles of diet of which pellagrins are deprived.
Leaves of plants contain it in abundance, while with seeds it is
present in less degree and then contained in the embryo, which
latter is lost in milling. Millet contains an exceptionally large
amount of fat soluble A and it is well known that in Egypt those
living on millet instead of maize escape pellagra. The protein of
millet has a high biological value which is the reverse with that
of maize. It should be noted that besides vitamine and protein
deficiencies the lack of inorganic salts should be considered.
_Protein Deficiency._—Animal protein is a superior protein and
maize protein an inferior one. Wilson grades proteins according to
their assimilability and taking meat protein as 1 he assigns to
maize protein a relative value of 3.4, which means that one must
consume 3.4 times as much maize protein as that of meat to obtain
the necessary protein requirements. Thirty grams of animal protein
daily is sufficient to maintain nitrogenous equilibrium but Wilson
considers 40 as a minimum B. P. V. (Biological protein value). We
should have to consume 136 grams of maize protein to obtain a B. P.
value of 40. Where hard labour is required the B. P. V. should be
50 and when associated with chronic intestinal disease it should be
as high as 60.
Wilson noted a B. P. V. of 23 for males in the diet which caused an
outbreak of pellagra in Armenian refugees at Port Said. The diet of
the pellagrous Turkish prisoners in Egypt had a B. P. V. of 33.5.
It may be stated that zein, the protein of maize, is deficient in
tryptophane and lysine, two important amino-acids necessary for
proper nutrition. Chick apparently produced pellagra in a monkey
fed on a low protein diet (Total protein 8.2 grams, of which all
but 2.7 grams was from zein.). The monkey was given an abundance of
accessory food substances in butter, marmite and orange juice.
_Amino-acid Deficiency._—In a recent paper Goldberger and Tanner
note that a low biological protein value is not necessarily
indicative of a pellagra-producing diet. In a series of experiments
the deficiency of vitamines did not seem to be related to pellagra
production and the same was true of the mineral elements. In
studying the nature of low protein biological values they were of
the opinion that this rested in certain amino-acid deficiencies in
the proteins consumed by the pellagrins. Benefit seemed to result
from administering cystine to two cases of pellagra and in a third
case there was steady improvement following the giving of both
cystine and tryptophane.
It is a question whether zein, the principal protein of maize,
contains any cystine.
Goldberger and his colleagues, after a careful investigation of
pellagra epidemiology, decided that such facts as the complete
absence of the disease among the nurses and attendants of the
pellagrous insane, or among the prison guards of institutions where
pellagra prevailed extensively, as well as among those caring for
pellagrous orphans, indicated that a dietary factor rather than
an infectious one was operative in the disease. Even where it was
stated that attendants and inmates of institutions had the same
dietary investigation indicated that as a matter of fact the insane
and the prisoners were not as well fed as the other group. Then too
the insane frequently fail to avail themselves of the food provided.
A study of the records of the Army and Navy of the United States
failed to show that a single case of pellagra had ever developed
among the personnel, although large numbers of the men came from
pellagrous districts of the South. This exemption they thought due to
the generous service ration.
In an investigation of the diet of the workingman’s family in the
North and South it was found that the southern one consumed much
larger quantities of starches and fats than the northern one, but
less fresh meat. In the family of the cotton mill operative, a
class showing a great incidence of pellagra, corn bread, flour
biscuits, and fat pork were the chief articles of diet. There is
a great deal of ancylostomiasis among these cotton mill people
and the debilitating effect of this disease may predispose to
pellagra. The general rise in the cost of food and, in particular,
the disproportionate increase in price of meats over cereals, since
1907, may explain the greater incidence of the disease since that
time. The wages of southern mill operators have also suffered on
account of frequent periods of financial depression during the last
ten years, thus causing them to buy cereals rather than meats.
_Goldberger’s Experiment._—In February, 1915, Goldberger started
a “pellagra squad,” consisting of 11 prisoners on a diet of wheat
flour (patent), corn meal, corn grits, corn starch, polished rice,
granulated sugar, cane syrup, sweet potatoes, fat fried out of salt
pork, cabbage, collards, turnip greens and coffee. Baking powder was
used for making biscuits and corn bread. The food value of each man’s
diet averaged 2952 calories.
A control was carried out with prisoners on a normal diet. The
experiment was continued until Oct. 31, 1915. Of the 11 volunteers
on the excessive carbohydrate diet six developed symptoms. Loss
of weight and strength and mild neurasthenia were early symptoms.
Definite cutaneous manifestations appeared only after five months.
The skin lesions were first noted on the scrotum, later appearing
on backs of hands in two cases and back of neck in one case.
There are those who believe that the methods of preserving foods,
cereal or proteid, by sterilizing at high temperatures, destroy
the vitamines so essential to proper metabolism so that people
who subsist extensively on canned vegetables and preserved meats,
instead of fresh meats and vegetables, may develop pellagra.
Evidence of this sort is obtainable in the mill villages of the
Southern States of the United States where pellagra is so very
prevalent.
We are now beginning to recognize that slight and vague digestive
trouble may be pellagrous in nature although never going on to the
development of the cutaneous, neurological and alimentary tract
diagnostic triad of symptoms.
Again there would appear to be efficient resistance to pellagra
in those who are in good physical condition, but when reduced
by illness, or the effects of poor diet and defective hygienic
surroundings, they may develop it. There are those who think that
hookworm disease is an important factor in predisposing to pellagra.
Not only does alcoholism, when coexistent with pellagra, make for
a bad prognosis but there are many who think that any abuse of
alcohol predisposes to pellagra. Against this however is the fact
that pellagra in the United States is about five times as common
among women as among men. It is generally recognized that pregnancy
and lactation predispose to pellagra.
_Pellagra in Turkish and German Prisoners._—There were (up to
the close of 1919) 9257 cases of pellagra among 105,668 Turkish
prisoners (1 in 11) and 79 cases among 7606 German prisoners (1
in 96). The Turkish prisoners had been on a deficient diet before
capture and the diet after capture had a B. P. V. of 33.5. The
labour group of the prisoners had a B. P. V. of 36.8 and the
disease was much more prevalent among them than in those not
working. Hammond-Searle notes that the diet of the nonworking
European prisoners was probably insufficient to prevent pellagra.
On the average the disease appeared among the German prisoners 4½
months after capture. They stated that while in Turkey their diet
had been excellent but almost all had suffered from dysentery or
malaria. In the Turkish prisoners diarrhoea was a prominent feature
and Bigland suggests a possible toxin action resulting from a
damaged intestinal mucosa. Stools from pellagrous Turkish prisoners
showed organisms similar to _B. perfringens_ in 90% of cases while
such organisms were not found in the stools of healthy prisoners.
_The Zeistic Views._—The idea which was at one time entertained
that maize, whether good or bad, brought on pellagra has now been
generally abandoned, owing to investigations, which proved that corn
possessed a fair nutritive value and was easily assimilable, together
with evidence to show that where care was taken in the maturing of
the grain and the prevention of decomposition by moulds or bacteria,
pellagra was either nonexistent or diminished in a district where
such measures were instituted.
The statement is frequently seen that pellagra did not make its
appearance in Europe until after the introduction of maize,
subsequent to the discovery of the New World. There are authors who
think Casal was suspicious of a maize dietary.
The zeistic views now incorporate some additional factor with the
basic one of a rather exclusive maize dietary.
1. The verderame theory of Ballardini. From noting on the corn
grains a covering with a greenish mould, Ballardini in 1845
advanced the view that pellagra was due to this mould and from
this time on we have the so-called zeitoxic views, which hold that
pellagra is caused by spoiled corn. Ceni and Fossati regard a toxin
elaborated by various moulds as causative. The fungi toward which
attention has been chiefly directed are _Aspergillus fumigatus_ and
_A. flavescens_ as well as certain species of _Penicillium_ and
_Mucor_.
2. The Lombroso view that as a result of the action of moulds or
bacteria, toxins are elaborated which, when ingested, give rise to
the disease.
3. That the toxins have origin in the action of various organisms,
especially _B. coli_, on the ingested corn, while in the intestines.
4. Recently views have been brought forward that pellagra is an
anaphylactic phenomenon connected with sensitization to the maize
proteins.
5. Rabitschek has brought forward a photodynamic theory which is
that pellagra is due to a preponderating maize or possibly other
cereal dietary which results in certain photodynamic substances
being introduced into the circulation. These substances become
toxic under the influence of sunlight. Hirschfelder has failed to
find any fluorescent body in the serum of five patients suffering
with severe pellagra.
Among arguments in favor of the maize etiology of pellagra may be
mentioned the following:
(_a_) Among the natives of Upper Egypt, where millet instead of
maize is the staple cereal, pellagra is rare, while in Lower Egypt
where much maize is eaten the disease is far more prevalent.
(_b_) While the natives of Corfu, prior to 1857, grew their own
maize and ate only sound grains there was no pellagra but later,
when the corn crop was less profitable, and the grain was imported
from Roumania, much spoiled maize was brought in and pellagra made
its appearance.
(_c_) Alsberg has shown that in recent years new methods of
harvesting corn have become common in the Southern States of the
United States. Instead of topping the corn it is cut and shocked
with the result that conditions are more favorable for the spoiling
of the corn. He also notes that varieties of corn are now planted
which have a greater oil content, which means a larger embryo, and
that it is this embryo which most easily spoils. Again he notes
that much corn is now raised in Northern States where the season
is shorter, so that there is a greater probability of immature
corn being marketed. All of these facts might explain the recent
appearance of pellagra in the U. S. and its previous nonexistence.
Thomas has shown that where 30 grams of a _superior protein_, such
as that of meat, would suffice, it would require 102 grams of corn
protein, an _inferior protein_. This inferiority is due to a lack
of assimilability of the amino-acids of corn protein. Protein
deficiency is the outstanding feature of a pellagra-producing diet
and in the corn protein we have one of inferior value.
_The Antizeistic Views._—As a rule the advocates of nonimportance
of maize in the production of pellagra hold that we are dealing with
an infectious disease and that it can only come into existence by
transmission from some other case.
1. The Thompson-McFadden Commission, while holding a very
conservative attitude, feel that certain faecal bacteria may be the
etiological factors.
2. Alessandrini believes that the causative factor may be present
in certain waters.
These views are that colloidal silica in water is responsible
for the disease. Voegtlin noted the great amount of aluminium
in certain vegetables and suggested this as the toxic causative
substance. A mixture of colloidal alumina and silica in water is
supposed to be operative as well as silica alone. Against the
colloidal silica hypothesis is the statement of Sandwith that the
water of the Nile, the drinking water of Egypt, is low in colloidal
silica content.
3. Long has suggested that amoebae may be the cause.
4. Tizzoni has incriminated a streptobacillus which he stated he
found in the blood and organs of pellagrins as well as growing on
maize.
=Epidemiology.=—As the result of very careful epidemiological
studies the Thompson-McFadden Pellagra Commission came to the
conclusion that there was evidence against the transmission of
pellagra by ticks, lice, bedbugs, cockroaches, fleas, mosquitoes and
buffalo gnats (_Simulium_).
They were rather disposed to consider that the disease showed a
greater prevalence where the disposal of faeces was unhygienic, as
in unsanitary privies, and that the existence of an efficient water
sewerage system prevented pellagra. If faecal bacteria should act
as infectious agents then the house fly would possibly be worthy of
suspicion.
Many of the peculiarities of sex and place distribution could be
explained by the stable fly, _Stomoxys calcitrans_, a fly which
bites viciously in the district in which they worked. This fly
bites only by day and is intimately associated with human dwellings
so that the greater incidence of the disease in the women, who stay
at home, as against an incidence five times less in the men who
work in the mill during the day might be explained by _Stomoxys_
bites.
At the same time their failure to transmit pellagra to monkeys by
injections of defibrinated pellagra blood would militate against any
infectious agent existing in the blood. It may be stated that Harris
has claimed to have produced a disease resembling pellagra in two
monkeys by injecting filtrates from emulsions of brain, skin and
intestinal tract of cases dying of pellagra.
Lavinder and Francis injected 79 monkeys and 3 baboons with varying
material from pellagra autopsies. Some of the animals were injected
with emulsions or Berkefeld filtrates of such emulsions made from
brain and cord. Other monkeys were inoculated with material from
skin similarly prepared, others with stomach and mouth mucosal
emulsions, and still others with intestine and faeces emulsions.
Blood, urine and cerebro-spinal fluid were also injected. Feeding
experiments were also carried out. With one exception, and that one
only suggestive of pellagra, the experiments were negative.
Sixteen volunteers, working under Goldberger, tried to infect
themselves with blood, nasopharyngeal secretions, epidermal scales,
feces and urine from pellagrins. Various atria of infection were
tried according to material; blood by intramuscular injection,
excreta by mouth. After a period of six months all the subjects of
the experiments remained well. _This evidence is certainly against
the infectious nature of the disease._
_Greater Prevalence in Women_.—Now that we attach no weight to
insect transmission of pellagra we have only the debilitating effects
of menstruation, pregnancy and lactation to explain the marked
susceptibility shown by women of from seventeen to forty years of
age. Before and beyond these ages the incidence in males and females
is about the same.
Before Goldberger began his experiments he was struck by the
relation poverty had to pellagra epidemiology, and as diet is the
chief element differentiating poverty and affluence, he chose this
line of research with the results recorded under etiology. His
explanation of the greater incidence in adult females, especially
wives and mothers, was their act of denying themselves the more
desirable parts of the food.
Sandwith has noted the great frequency of pellagra in hookworm
patients, thus of 300 such cases in Egypt, 46% had pellagra.
The Thompson-McFadden Commission was unable to note any evidence
that would distinctly point to corn, good or bad, as giving rise to
pellagra outbreaks. They did note, however, a very limited use of
fresh meats.
PATHOLOGY AND MORBID ANATOMY
There is nothing very constant or characteristic in the pathological
changes of pellagra. In the second stage the urine shows an
indicanuria and the faeces an abundance of skatol. The examination of
the gastric contents gives findings of anacidity and deficiency in
pepsin. The HCl deficiency probably causes disturbance of pancreatic
efficiency leading to mal-assimilation of fats and proteins.
The blood shows a moderate lymphocytosis but not an increase in the
percentage of the large mononuclears as has been claimed by the
adherents of the protozoon theory.
At autopsy we find rather marked emaciation. The wasting of all
organs seems to be greater than in any other wasting disease. The
skin lesions show degenerative changes in the corium with slight
cellular infiltration. In the epidermis there is superficial
atrophy but still some thickening in the stratum granulosum.
Warthin states that the lesions are those of a chronic
intoxication. The spleen shows atrophy and in the follicles there
is necrosis of germ cells as well as hyaline changes. The liver and
kidneys often show fatty change. In general the changes are those
of a senile character. There is atrophy of the mucosa of the small
intestines and there may be small ulcers present.
The mesenteric glands are enlarged. Roaf has noted the presence
of involvement of the adrenals and the Committee investigating
pellagra in Turkish prisoners found a marked supra-renal inadequacy.
Macroscopically no changes are seen in the central nervous system but
histologically we often note chromatolysis with bulging of borders,
eccentric nucleus and disappearance of tigroid substance in various
nerve cells, especially those of the anterior horn, posterior
ganglia, Clark’s column and Betz cells of cortex. There is an absence
of chronic meningo-encephalitis and meningo-myelitis which should be
present in the general type of protozoal infective lesions.
Degenerations in the posterior columns and crossed pyramidal tracts
have been reported from certain autopsies.
The cell count of the cerebro-spinal fluid is normal and there is
usually an absence of globulin increase with a negative Wassermann.
The blood chemistry findings in pellagra appear solely to be low
nonprotein nitrogen and urea values.
SYMPTOMATOLOGY
There is probably no other disease which shows such a multiplicity of
symptoms and such variations in these symptoms.
Upon questioning a patient who has developed a pellagra eruption in
the spring months there is often obtained a history of more or less
prolonged neurasthenic manifestations during the preceding winter,
chiefly dizziness, insomnia, apprehension, occipital heaviness and
muscular fatigue. There may also have been previous sensitiveness of
the mouth and slight epigastric discomfort. Along with the appearance
of the eruption we may have more marked alimentary tract disorders
consisting of stomatitis, gastric disturbances, especially pyrosis,
with a recurring diarrhoea. Upon examining the eruption we note
localized, sharply delimited, strikingly symmetrical skin lesions of
those parts of the body which are chiefly exposed to the sun’s rays.
This erythema is very similar to sunburn but often follows
inadequate exposure to the sun and the erythema persists instead
of fading. Desquamation continues for weeks or months instead of
healing. The dry scaling area usually shows a striking pigmentation
at the borders even after the central portions of the erythema have
cleared up. The skin lesions instead of being dry and atrophic as
is usual may more rarely be moist and oedematous.
From a vague neurasthenia we have now more distinct neurological
manifestations such as variations in the reflexes, tremors,
especially of tongue, head and upper extremities and a depressed
mental state with lack of mental concentration or lapses of memory.
Later on we may have a toxic psychosis in which mutism is often noted
in a mental state characteristically melancholic.
[Illustration: FIG. 84.—Marked symmetry of all lesions. Illinois
case. (From Lavinder and Babcock.)]
A final cachexia, with dementia, loss of control of the vesical
sphincter and a terminal diarrhoea, marks the end. Recurrences of
clinical manifestations each spring, or possibly skipping a year,
are striking features of the disease. While the skin and alimentary
tract disturbances are usually in abeyance in the winter, this
holds to less degree with the nervous symptoms.
THE DIAGNOSTIC TRIAD
We may then state that in a typical case we have the diagnostic
triad or pellagrous symptom-complex of (1) symmetrical sharply
delimited erythemas of certain portions of the skin surface exposed
to the sun with (2) alimentary tract disturbances of stomatitis,
epigastric and substernal soreness and burning, with pyrosis and a
recurring diarrhoea and (3) neurological manifestations in which a
prodromal neurasthenia is followed by paraesthesias, in which burning
sensations are prominent, at times leading to suicide by drowning,
with alterations of deep reflexes, tremors and, in more advanced
stages, a confusional insanity.
Burning sensations are noted in mouth, gullet and stomach as well
as of the skin. Then too a burning sensation may be complained of
in the area formerly the seat of a pellagrous eruption. The palms
of the hands and soles of the feet often give a burning sensation.
One of the characteristic features of pellagra is the periodic
recurrences in spring, with almost complete cessation of skin and
alimentary tract symptoms in the winter and, again, the tendency
in many cases for one group of symptoms to overshadow the symptoms
which usually accompany them. These periodic recurrences may well
be associated with seasonal variation in diet.
=Stages in Pellagra.=—For many reasons it is peculiarly difficult
to recognize stages but for convenience many authors describe the
disease under a prodromal, 1st, 2d and 3d stage.
These stages have reference solely to the degree of severity of the
manifestations and a case may never progress beyond the 1st stage,
although recurring for a number of years. Again a case may rapidly
progress to the 2d stage and even run through the 3d or cachectic
stage in a few months. We must not consider these stages as tending
to follow in sequence as we do in connection with the stages of
syphilis.
_The prodromal manifestations_ of neurasthenia, malaise, loss of
weight, loss of strength, vertigo and digestive disturbances would
be suited to many other diseases, especially tuberculosis, and they
are rarely recognized as belonging to pellagra until the appearance
of typical skin or other symptoms brings about their association with
pellagra. There is little definite information as to the period of
incubation although Sandwith places it at from nine to twelve months.
In Goldberger’s cases the eruption did not appear until after five
months on the experimental diet. In the study of cases of pellagra
occurring among Armenian refugees, and in Turkish prisoners of
war, oedema was not infrequently noted and its occurrence usually
preceded the eruption.
=First Stage.=—In the first stage we note the alimentary tract
disturbances of sodden fissured conditions at the angles of the
mouth, a large indented tongue with central coating and bare
glistening sides and tips, often with a shiny mucus coating these
red borders and a red buccal mucosa. The fungiform papillae appear
as pinhead red elevations. Later on the tongue becomes bare, red and
fissured. There is often an increased flow of saliva. Aphthous ulcers
are less common than in sprue. The gums are often quite tender and in
cases where they are somewhat spongy and swollen, with a tendency to
bleed, we note the appropriateness of “Alpine scurvy” as a synonym
for pellagra.
In cases with very severe stomatitis there may be enlargement
of the salivary glands. The pharynx is congested and a similar
condition of the oesophagus gives rise to a burning sensation which
is often described by the patient as going up the gullet from the
stomach.
Gastric disturbances, especially gastralgia, pyrosis and
eructations, may be pronounced. Anacidity and deficiency of
pepsin are noted in gastric juice examinations. The intestinal
symptoms are those of recurring diarrhoea or occasionally of a mild
dysentery but in many cases there is a normal functioning of the
bowels. Although the skin manifestations usually follow those of
the alimentary tract they may precede them or occur simultaneously.
_The Eruption._—It is usual to designate the skin lesions of the
first stage as erythematous, in that they resemble a sunburn. These
pellagrous eruptions may follow some source of skin irritation as
well as that from exposure to the sun; thus the perianal, perineal,
vulvar, and even scrotal regions may show a marked erythema from
the slight irritation of the rubbing of clothes or opposite parts.
Chemical irritants may also be operative.
The pellagrous erythema shows itself most commonly during the late
spring or early summer. It may appear in the early spring or late
summer or early fall, but only exceptionally does it occur in the
winter. There are, however, alterations in the skin previously
involved which can at times be noted during the winter.
The typical eruption, however, is that which shows itself on the
backs of the hands or running up beyond the wrist to the lower third
of the forearm. The phalanges and especially the knuckles may also
show the eruption. On the face the eruption is most common over
the bridge of the nose, on the cheeks and forehead. There may be
spots back of the ears or on the nape of the neck. Occasionally the
butterfly outline of lupus erythematosus is seen. The face may show
the so-called pellagrous mask. On the neck we may have a band-like
eruption extending to the upper part of the sternum (Casal’s
necklace) or the erythema may extend down the sternum (cravat).
[Illustration: FIG. 85.—Dry dermatitis on face, hand, neck and upper
chest. Egyptian case. (From Lavinder and Babcock.)]
Very important were the observations of Goldberger that in his
six experimental cases the eruption first showed itself as a
symmetrical involvement of the sides of the scrotum.
On the feet the dorsal eruption does not usually go above the
malleoli and rarely involves the dorsal surfaces of the external
toes although rather commonly affecting the great toe. In the U. S.
the eruption may extend up the front and back of the leg (boot).
The soles of the feet and palms of the hands are not infrequently
involved in American cases as is also true of the tip of the elbow.
The eruption on the elbows rarely occurs until the patient takes
to his bed and is probably incident to irritation over olecranon.
Sandwith states that the skin lesions in Egypt are more widespread
than those seen in Italy.
These skin eruptions show striking symmetry, marked delimitation from
unaffected skin, with often more intense pigmentation at the border
line, and they burn rather than itch.
[Illustration: FIG. 86.—“Butterfly” eruption on face of child two
years old. (Deaderick and Thompson.)]
In 1679 cases of pellagra Merk found 77% with eruption solely on
backs of hands, 13% on backs of hands and neck, 8% on neck alone.
The eruptions on dorsal surfaces of feet and calves of legs are
chiefly seen in barefooted children. In the pellagra cases among
Turkish prisoners Bigland noted an eruption on the hands in all
but one of 232 cases. Rashes on the feet were noted in 111 cases
and rashes on the face with bilateral symmetry were observed in 47
cases. One case showed a scrotal eruption.
The more advanced skin lesions are those of a dermatitis rather
than an erythema. The affected skin is at first of a dull red
color like a sunburn and later becomes reddish-brown or livid
or chocolate-colored. Fox has likened the eruption to that of a
carbolic acid burn.
The normal elasticity is lost and the area appears as a dry, scaly,
atrophic patch—it is the skin of a very old man. The moist
oedematous skin lesions are far more common in the U. S. than
elsewhere and may show bullae and even gangrene. Such cases may
show the gauntlet desquamation.
_The nervous symptoms_ of this stage are chiefly vertigo, headaches,
which are usually occipital, and depression of spirits. Insomnia may
be a marked feature. Lack of mental concentration is often noted.
=Second Stage.=—In the second stage we have a continuation and
aggravation of the skin and alimentary tract symptoms with pronounced
neurological manifestations. Tremors of the tongue and hands appear.
There is great muscular weakness of the legs. Paraesthesias in great
variety are common. Pain on pressure in the dorsal and lumbar regions
of the back is common. The gait is more that of marked muscular
weakness.
Attacks of giddiness with tendency to fall forward or backward are
often reported. The deep reflexes may show variations from normal
and there may be variations in the reflexes of the two sides, thus
the patellar reflex on one side may be exaggerated and that on the
other normal or diminished. Ankle clonus is rare. Neurological
manifestations are slight in pellagrous children, the main symptoms
being the cutaneous ones.
The mental state is confused and the patient shows depression
and is often morose. The most common psychosis is that of simple
retardation. The patient answers questions in monosyllables and in a
low tone of voice after a more or less prolonged delay. Goldberger
states that mental disturbances sufficient to require institutional
care do not occur in more than 2 or 3% of cases.
In the second stage the urine shows rather marked indicanuria and
the faeces contain an excess of skatol. Loss of weight is as marked
a feature of pellagra as of tuberculosis. Well nourished pellagrins
are the exceptions.
=Third Stage.=—With the setting in of a confusional insanity and a
terminal cachexia we have the third and last stage of the disease.
On account of so many of the victims of pellagra becoming inmates of
insane asylums the disease is peculiarly dreaded.
[Illustration: FIG. 87.—Wet dermatitis. Localization usual. Hands
oedematous. Cachectic state. South Carolina case. (From Lavinder and
Babcock.)]
Pellagra often runs a rather acute course in the U. S., the patient
dying within two or three months. The usual course in Europe is one
prolonged over years, with at times intermissions covering one or
more years.
A form of pellagra known as typhoid pellagra often shows a high
fever with symptoms more or less resembling a very toxic case of
typhoid.
A mental state resembling the acute delirium of paresis may be
present. Such states are often terminal. The usual course of
pellagra is afebrile. Such terms as _pellagra sine pellagra_
are given to cases which may not show the skin lesions and the
designation _pseudopellagra_ has usually been used by those who
insist upon limiting the name pellagra to those cases which fit
in with their special etiological views so that cases clinically
pellagra but in which the special etiological factor does not
obtain are called pseudopellagra.
Symptoms in Detail
The cutaneous neurological and alimentary tract disturbances have
each already been separately described in detail.
_The Blood._—Hillman has made very careful blood examinations
of a series of cases and found a variable degree of chloranaemia
which however, was not a prominent feature. He notes the occasional
occurrence of a leucocytosis in the course of the disease. As a
rule there is a definite lymphocytosis, the average percentage
of lymphocytes being 33.99. The average percentage for the large
mononuclears was 2.59. The average percentage of eosinophiles was
2.73. The determinations of the coagulation time of the blood gave
normal figures.
In Ridlon’s series the average red count was 4,720,000, the
white count varied from 14,200 to 4200, average 8027. The
polymorphonuclear percentage averaged 68.2, that of lymphocytes 21,
of large mononuclears 8 and of eosinophiles 2.
Hb percentage averaged 77 and color index 0.81. The blood serum
failed to give positive Wassermann reactions.
_The Urine._—There is rarely any increase in albumin. The most
important urinary finding is in connection with indicanuria, 96.4%
of Ridlon’s cases showing this finding. As convalescence comes on
indicanuria tends to lessen.
_The Temperature Chart._—We expect a normal temperature in an
uncomplicated case of pellagra but in typhoid pellagra and in the
terminal stages of the disease a fever of from 101° to 103°F. is
generally noted. Fever makes for a bad prognosis. There is nothing
special about the circulatory system other than low blood pressure
and a tendency to vasomotor disturbances. With the genito-urinary
system other than the rather marked indicanuria, there is nothing
of note.
DIAGNOSIS
In the presence of the diagnostic triad of cutaneous, nervous and
alimentary tract manifestations there is little difficulty in
diagnosis but when the skin lesions are absent or only slightly
developed the difficulty is great. One of the most important points
in diagnosis is a history of preceding attacks.
There is no reliable laboratory test and the reports as to positive
reactions following injections of maize extracts seem unreliable.
Again there do not seem to be any antibodies in the serum of
pellagrins which can be utilized in serological diagnosis. A
primary requirement would be a suitable antigen. Competent workers
have been unable to find any bacterial organism in the blood of
pellagrins.
Erythema multiforme and dermatitis venenata seem to be the skin
diseases most liable to cause confusion.
In old people with arterio-sclerotic changes and consequent mental
symptoms there may be lesions of the hands or feet of more or less
gangrenous type, which may be a real source of confusion. The
lack of sharp delimitation of such lesions and the absence of the
pellagrous stomatitis should differentiate.
Poison ivy dermatitis, if bilateral, may be confusing, as may also
chapping of the hands.
In Italy a disease due to eating ergot-diseased rye meal and
called ergotism may be a source of confusion as this disease shows
gangrenous manifestations. The gangrene of ergotism is a dry one.
Sprue does not show the dermatitis, and the nervous manifestations
are solely those of irritability or possibly slight neurasthenia.
The sprue stool is not found in pellagra. See Diagnosis under Sprue.
Typhoid pellagra may be confused with severe typhoid fever or other
acute infectious diseases or with conditions associated with coma,
as diabetes or uraemia.
PROGNOSIS
It is a risk to venture a prognosis in pellagra because cases
that seem mild may suddenly become severe. The extent of the skin
lesions does not parallel the severity of the case although moist or
gangrenous dermatitis is usually seen only in severe cases.
When fever comes on the prognosis of the case is unfavorable and
when the mental manifestations are prominent the prognosis is bad.
The Italian physicians give a more hopeful prognosis than the
American ones, which is easily understood when it is considered that
American mortality from pellagra is given as from 25 to 39.10%. That
of Italy is certainly below 10% and recent statistics have shown a
mortality of only 3%. In the U. S. the mortality is now below 10%.
Of particular importance is the question of the liability to mental
trouble. Singer states that about 40% of all cases of pellagra
develop mental disturbances and that this incidence is much higher
in cases presenting recurrences. In Italy it is estimated that from
5 to 10% of pellagrins become permanently insane.
The earlier a case of pellagra comes under treatment the more
favorable the prognosis.
In the first stage the prognosis is very good but in the second,
when there is more or less involvement of the central nervous
system, it is much less favorable. In the third stage, or that
of the terminal cachexia with marked mental deterioration, the
prognosis is extremely bad. Each recurring attack makes the
condition more serious. The older the patient the more serious the
prognosis.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—There does not seem to be any satisfactory evidence
as to the contagiousness of pellagra, so that any method involving
isolation is not indicated.
Even if the use of spoiled corn is not productive of pellagra it is
certainly advisable to prevent its sale by state regulation.
As a proper, well-balanced dietary is an important curative measure
it is therefore prophylactic.
=Treatment.=—In a disease which characteristically shows a marked
amelioration in the winter or a disappearance of symptoms for one or
more years we should be very conservative in attributing improvement
to any drug.
At the New York Post Graduate hospital, 17 cases were apparently
cured on rest in bed and full nutritious diet. Hospital treatment,
thereby removing the patients from the environment in which the
disease developed, is generally conceded of the greatest benefit.
It is always recommended by the advocates of some special drug
treatment that the patient be kept on a nutritious diet. Roussel in
1866 stated: “Without dietetic measures all remedies fail.”
Many authorities speak highly of arsenic in various forms as
Fowler’s solution, atoxyl, salvarsan, etc. Others are equally
pessimistic as to the value of arsenic in any form.
Niles is a strong advocate of hydrotherapeutic measures. He
recommends the drinking of two to six glasses of tepid water daily as
well as colon irrigations, cold abdominal compresses, hot packs and
saline baths.
Deeks prefers to eliminate sugar and starchy food from the dietary
of pellagrins for a few days at a time and to give fresh fruit
juices, with broths and milk. He highly recommends dilute nitric
acid, well diluted, before meals. As there is almost constantly
anacidity and pepsin deficiency in the gastric juice it would seem
that this condition should be treated.
It is advisable to keep the patient out of the sun and require him
to take his exercise after sunset.
Dyer recommends ½ to 1 ounce gelatin daily together with the juice of
two or more oranges or lemons. He prefers a diet of eggs, milk and
well-cooked vegetables. He also gives quinine hydrobromate in 3 grain
doses 3 times daily.
Psychotherapy seems to be of importance in the treatment of
pellagra.
Lavinder says that many people have pellagra because they have some
other condition and when this is cured the pellagra is also cured.
In truth, pellagra is very rarely a primary condition. We must then
give careful attention to the predisposing causes which may not only
be ancylostomiasis, alcoholism, or malaria, but, as well, various
gynaecological or alimentary tract disorders.
With the colloidal silica etiology in view Allesandrino has
recommended sodium citrate in treatment.
Goldberger has cited the following as showing the influence of diet:
In an orphan asylum with 211 orphans, 68, or 32%, had pellagra.
These children were divided into 3 groups and given different
rations, those under six years of age receiving milk and eggs,
while those over twelve years were given meat, as they assisted in
the work of the institution. The children between six and twelve
lived practically on a vegetarian diet in which corn products
and syrup preponderated with deficiency of legumes. Of 25 young
children only 2 showed pellagra, and there was but 1 case in the
66 children over twelve years of age while the 120 between six and
twelve gave 65 cases or 52%.
As the result of increasing the milk supply, so that every child
under twelve years got a pint daily, also at least one egg daily,
together with an increase in the use of beans and peas, as well as
fresh meat, the disease was entirely eradicated. The corn elements
of the diet were reduced but not excluded. There was increase in
proteins and a decrease of carbohydrates.
As to the diet in pellagra Niles recommends the exclusion of
all maize articles of diet. He recommends meat, eggs, milk or
buttermilk with peas and beans. When intestinal symptoms are
severe he gives barley gruel, rice-water, thick broths and dry
meat powders. As a drug treatment for diarrhoea he uses bismuth
beta-naphthol.
Babcock, recognizing the importance of the treatment of the
pellagrous neurasthenia, recommends the Weir-Mitchell plan of
prolonged rest in bed, nutrition, hydrotherapy and hygienic
measures. “Fat and blood” should be our aims and he notes the value
of cacodylate of soda in increasing fat. He also refers to the
susceptibility to suggestion of pellagrins and is an advocate of
psychotherapy.
Having in mind the vitamine deficiency view Voegtlin has treated
cases of pellagra with extracts of substances rich in vitamines.
Extracts prepared from fresh ox liver and fresh hog thymus caused
definite improvement in pellagrins so treated while extracts of
yeast and rice polishings seemed to be without value. It will be
remembered that the glands of animals are rich in fat soluble
A. For the burning of the erythema Niles recommends a lotion of
calamine (4 drams), powdered zinc oxide (3 drams), in 1 pint of
lime water. As regards climatic treatment the same authority
believes that a colder climate is indicated and that a patient with
pellagra should avoid hot weather for a year after all symptoms
have disappeared.
CHAPTER XX
SPRUE
DEFINITION AND SYNONYMS
=Definition.=—Under the designation sprue we have a form of chronic
diarrhoea characterized by periods of improvement alternating with
a return to the previous condition. The disease is afebrile, of
insidious onset and first manifests itself by soreness of the buccal
mucosa and vague digestive disturbances.
The soreness of mouth and gullet is soon followed by erosions,
especially at the site of the posterior molars, and a bare raw
tongue. Exceedingly characteristic are the voluminous, frothy
stools which are evacuated chiefly in the morning hours. The
patient becomes weak, emaciated, irritable and of an earthy pallor.
The disease chiefly affects Europeans who have lived in Southern
China, Cochin China and Java, and unless treated early tends to
progress to a fatal termination.
=Synonyms.=—The word sprue is a corruption of the Dutch term “spruw”
used to designate this tropical aphtha or aphthous stomatitis. The
name psilosis, meaning bare, was suggested by Thin and is the term
employed in many books instead of the better recognized designation,
sprue.
Other designations are: Chronic diarrhoea of the tropics, Ceylon sore
mouth and Cochin China diarrhoea.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—The French (1868-1872) described this disease under
the name of chronic or endemic diarrhoea of Cochin China and noted
its resemblance to Moore’s “Hill Diarrhoea.” In 1876 Normand
incorrectly associated _Strongyloides_ with the disease.
The physicians of the Dutch East Indies described the disease under
the designation “spruw” and Manson in a very complete description
of the disease called it “sprue,” a corruption of the Dutch name.
It is interesting to note that Hillary in 1766, described a similar
disease of Barbadoes, W. I., which he called aphthoides chronica.
=Geographical Distribution.=—It is particularly prevalent in South
China and the East Indies. India and Ceylon are also regions of
the disease. In the West Indies it has been carefully studied, in
Porto Rico by Ashford, and of particular interest is the fact that
Wood has recently insisted on the presence of sprue in the Southern
States of the U. S. The Philippines and tropical Africa are also
sections from which the disease is reported.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—The cause is unknown. The disease makes its appearance
chiefly in Europeans who have lived many years in the tropics and may
not show itself until the patient has returned home. (In one case
reported by Thin seventeen years after the return home.)
It seems to select those who are weakened by dysentery or other
debilitating diseases, or who are compelled to subsist on
indigestible food or to lead a life of exposure to hardships.
Women in whom the menstrual flow is excessive or who are in the
period of lactation seem to be especially susceptible. Some think
alcoholics more susceptible. The idea has been advanced that the
abuse of calomel has been a factor and this view is one to be given
weight because it is well recognized that at the present there is
much less sprue than formerly and with this there has been a more
rational use of calomel. The excessive use of highly seasoned food,
so common with Europeans in the tropics, may have an influence.
Some have thought that sprue was the manifestation of a tropical
pancreas; at first congestion and later exhaustion of its function.
The character of the stools lends support to this view.
At one time it was thought that _Strongyloides stercoralis_ was the
cause; this idea had its origin in the finding of these larvae in
the stools of a patient with Cochin China diarrhoea.
Certain authors have considered bacteria giving a granulose
staining reaction as the cause while others have thought cocci to
be concerned.
Kohlbrugge found organisms resembling _Oidium albicans_ in the
intestines, oesophagus and tongue. He found similar organisms in
the stools and tongue scrapings of cases of sprue. Beneke found
bacilli in the tongue, oesophagus and intestines and considered
these as causative, regarding the thrush-like membranous deposit as
connected with the cachectic state and not causative.
Bahr is inclined to believe that _Monilia albicans_ (_Oidium
albicans_) is the cause, as he found these saccharomycetes in the
deep layers of the tongue, in the mucoid coating of the intestines
and in the deposit in the oesophagus. He thinks it the ordinary
thrush species which may take on greater virulence in the tropics.
Ashford states that he has found a species of _Monilia_, different
from that of thrush, almost constantly in tongue scrapings and
stools of sprue cases and he regards this species as the cause of
sprue. He states that this organism is common in Porto Rico bread
and thinks it possible that the disease is transmitted in this way.
It has been called _Parasaccharomyces ashfordi_. It is a round
yeast, 4 to 7 microns in diameter. Wood has recently expressed the
view that sprue is not infrequently mistaken for pellagra in the
Southern United States.
Castellani, in a study of moulds of the genus _Monilia_ in sprue
stools, holds them responsible for the excessive gas production,
although not the cause of the disease. Various protozoa, as amoebae
and spirochaetes, have been considered as possible causes.
While there does not seem to be any vitamine deficiency implicated
yet there is disordered assimilation, which may be due to
alimentary tract infection or to insufficiency of pancreatic
functioning. It has been suggested that secretin deficiency is the
essential disturbance.
=Epidemiology.=—The disease is rare in natives and is entirely
endemic. Some authorities have suggested a greater frequency of the
disease in those intimately exposed to a case, as in husband and wife
or the members of a family.
Sprue is usually a disease of mature life and affects women more
frequently than men. While climate cannot be considered as causing
sprue yet the effects of hot climates in producing exhaustion
states in Europeans must be borne in mind. The sprue patient should
always leave a tropical climate.
PATHOLOGY AND MORBID ANATOMY
The changes in the alimentary tract apparently originate in the
structures lying beneath the epithelial coverings, thus indicating
that the toxic material acts through the blood rather than as a
surface irritant to the mucosa. At first there is congestion of the
underlying connective tissue with a round cell infiltration. Later
on the epithelial covering of the alimentary tract suffers and
auto-intoxication, as evidenced by indicanuria, becomes operative.
At autopsy the subcutaneous fat is found to have almost
disappeared. The intestines, especially the ileum, show marked
thinning, this atrophy especially affecting the mucosa, the surface
of which is covered by a layer of dirty gray mucus. The submucosa
generally shows connective-tissue increase. The gut is pale and
diaphanous. The solitary follicles may show as small cysts filled
with a gelatinous material or as ulcers.
The liver is markedly atrophied. The mesenteric glands are usually
enlarged. The pancreas may show cirrhotic changes.
SYMPTOMATOLOGY
=A Typical Case.=—It is very difficult to obtain definite
information as to the onset which is characteristically insidious.
There is usually first noted a sensitiveness of the buccal mucosa
so that alcoholic drinks and acid or highly seasoned food cannot be
taken without marked discomfort. A sense of fulness or distention in
the epigastric region is often an early symptom. Frequently there
is a history of a rather intractable morning diarrhoea which may
alternate with periods of constipation.
The diarrhoeal movements are remarkably copious and soon change
from bile-colored, liquid evacuations to the characteristic
putty-colored, pultaceous, gas bubble permeated, offensive stool
of sprue. While the patient experiences a sense of relief from
the evacuation of the fermenting mass yet there is at times an
excoriation about the anus which may cause pain when at stool.
Neuralgic pains of the region of the anus may be present late in
the disease.
When examined microscopically the stools are found to show much
fat, yeasts and undigested food. The fats are chiefly in the form
of neutral fats and fatty acids rather than as soaps. The reaction
is acid. Nausea and vomiting, especially about noon, may be
complained of.
While the characteristic stools best show the full development of the
disease there are also changes noted in tongue and buccal mucosa.
Following the marked sensitiveness of the mouth above noted there
soon appears a redness of the sides and tip of the tongue with a
glistening coating of the surface. Small vesicles later becoming
superficial erosions develop along the tongue borders, frenum and
buccal mucosa.
There is also congestion and swelling of the fungiform papillae.
Very characteristic are ulcers at the site of the rear molars
(Crombie’s ulcers). Later on the tongue becomes bare, fissured and
even glazed, as if varnished.
The gullet may be raw and very sensitive. The appetite is apt to be
capricious and the patient may be very intractable, insisting upon
dietary indiscretions which he knows will aggravate his condition.
There is a progressive loss of strength, weight and energy. The
liver progressively diminishes in size but is difficult to map out
owing to the bulging, dough-like abdominal contents. The urine is
usually free of albumen but shows marked indicanuria. Sprue is
characteristically afebrile.
Anaemia becomes marked, the red cells going as low at times as
under 2,000,000, per cmm. and the Hb. percentage less markedly
reduced (color index above 1). The polymorphonuclears are reduced
in percentage.
There is a tendency to depression and irritability.
The period during which sprue runs its course is very variable.
Some cases drag on for ten or twelve years while others may be
subacute in type, death ensuing within a year or two.
In addition to the typical or complete sprue described above Bahr
would add: (1) _Incomplete sprue_, in which with typical stools there
is no abnormal appearance of the tongue, and (2) _Tongue sprue_, in
which with characteristic mouth involvement there is absence of the
sprue stool.
Symptoms in Detail
_The Stomatitis._—At first we have a disagreeable bitter taste
in an unusually sensitive mouth. Later there develop superficial
ulcers along the sides and frenum of the tongue, which subsequently
involve the buccal mucosa. The gums may be quite tender and saliva
dribble from the mouth.
In the later stages the tongue becomes bare, red, fissured and
glazed.
_The Stools._—Commencing as early morning diarrhoea, with at times
alternating constipation, there gradually sets in that which makes
for a diagnosis of sprue—putty-colored, fermenting, offensive
stools which are extraordinarily copious.
They are also very fatty and of acid reaction. They show a proteid
loss as well as lack of fat absorption.
_The Blood Findings._—There is a marked secondary anaemia with
great reduction in red cells and Hb. percentage.
The color index averages higher than normal and with the
poikilocytosis resembles the blood picture of an atypical
pernicious anaemia. Nucleated reds are rarely found. The
eosinophiles are reduced in percentage. The polymorphonuclears
often show a great number of nodes, as 7 or 8 instead of the
ordinary three.
There is a mononuclear increase with polymorphonuclear reduction.
The white count is somewhat below normal—4000 to 6000.
_Other Features of the Disease._—The liver is notably diminished
in size. The urine shows indicanuria. The patient has a dry earthy
skin and may show oedema about ankles.
Mentally there is lack of concentration with marked irritability
and moroseness. Tetany has been reported as occurring rarely in
very severe cases. The abdomen is doughy and the temperature in the
later stages tends to become subnormal.
DIAGNOSIS
_Thrush_ is characterized by the membranous coating which
microscopically shows the fungus. It also is chiefly a disease of
children and those who live under wretched hygienic conditions and
with insufficient food. The characteristic stools are absent.
_Pellagra._—The stomatitis, diarrhoea and mental irritability are
very similar in the two diseases. There is, however, absence of the
sprue stools in pellagra and the periodical recurrence and skin
manifestations of pellagra are absent in sprue.
Wood thinks that in the absence of any evidences of organic nervous
disease in sprue we have an important differentiation as he finds
that pellagra has as great a tendency to invade the nervous system
as has syphilis. Salivation is marked in pellagra, not in sprue.
The two diseases, however, are best differentiated by the darker,
more fluid, less copious stool of pellagra as contrasted with the
copious, light colored stool of sprue. Stools containing great
amounts of undigested fat are most characteristic of sprue; fat
absorption in pellagra is about normal (95%) while in sprue it is
only about 75%.
_Syphilis_ with its buccal mucous patches or geographical tongue
may be mistaken for tongue sprue.
=Hill Diarrhoea.=—Many authorities do not consider this as a disease
distinct from sprue. The English, however, note the features of
its occurrence only at high altitudes; thus persons going to Simla
suffer from hill diarrhoea but upon their return to the sea level the
disease disappears. The characteristic features of hill diarrhoea
or Simla trot, as it is often called, are the passage of from 2 to
6 watery, whitish stools in the early morning hours. The patient is
usually free from diarrhoea in the afternoon. The color may resemble
that of freshly made whitewash, hence diarrhoea alba.
At first it is only the annoyance that is complained of but later
on the appetite is lost and the patient becomes weak.
There is an absence of the sprue mouth. The laboratory diagnosis,
other than the finding of excess of fatty acids, soaps, undigested
food remnants and yeasts is unimportant.
PROGNOSIS
While the disease responds to treatment in those who are not too far
advanced yet it always should be considered a serious affection. The
chances of a complete restoration to health are better for those who
can leave the tropics and reside permanently elsewhere.
TREATMENT
It is essential that the patient possess the will power to carry out
the course of treatment; the clothing should be of wool to prevent
chilling and the patient should remain in bed until his condition has
decidedly improved.
_The Milk Treatment._—A preliminary dose of castor oil is given
and when this acts the patient should begin taking milk as the sole
food. At first about 4 pints of skimmed milk are given daily. The
milk should be given in two-hour feedings, well warmed and taken
through a glass tube or with a teaspoon—it should not be drunk. As
the stools become less frothy the amount of milk is increased so
that the patient takes from 6 to 7 pints daily. Milk should be the
sole food for six weeks from the time the stools become solid and
the mouth symptoms disappear. Rele prefers buttermilk to skimmed
milk. Eggs are usually well borne after the milk course. Stale
bread or toast is cautiously added and then some fish or chicken.
At times the patient seems benefited by giving a meat treatment day
once or twice a week during the course of the milk treatment.
_Meat Treatment._—If the patient is very ill it may be advisable,
after the preliminary dose of castor oil, to give meat juice
obtained by expressing the juice from slightly broiled meat, about
2 teaspoonfuls every half hour. If possible however one starts in
with the meat cure, which is about 4 ounces of a lightly broiled
chopped-up beefsteak, every four hours. Raw meat is usually given
in this treatment but there is danger of _T. saginata_ infection.
At least 4 pints of warm water should be taken daily but not at the
same time the patient eats the meat. Rest in bed and the avoidance
of chilling are important measures. In all food treatments we
should avoid forcing the patient to eat—it is better to give food
only when the patient desires it.
Some prefer to alternate the milk treatment with the meat one.
_Fruit Treatment._—The patient is allowed fruit in great
abundance. Strawberries, peaches, grapes, ripe gooseberries
and fully ripe bananas are usually recommended. Papayas are
particularly well suited. Pomegranates are also highly recommended.
Sour or fibrous fruits should be avoided. Strawberries and milk are
highly advocated. Cooked strawberries or other cooked fruits do
not benefit the patient, the curative principle being apparently
destroyed by heating. At all times alcoholic drinks and highly
spiced foods should be avoided.
The only drug that has been advocated to any extent is yellow
santonin, in doses of 5 grains, night and morning. It is very
doubtful if any drug treatment is of the least value.
LeDantec, with the elimination of the granulose bacteria in mind,
has recommended the cutting off of carbohydrates and the giving
of a strictly albuminous diet. Subsequently he gives lactic acid
producers as contained in _Bacillus bulgaricus_ preparations.
Schmitter has recommended emetine in the treatment of sprue, but
Ashford has found this drug, as well as santonin, of negative
value. Brown has had success in treating a case of sprue with
pancreatin, 30 grains daily. Since then he has had marked success
in three other cases. He now combines the pancreatic extract with
calcium carbonate.
In connection with Ashford’s work with a specific _Monilia, M.
psilosis_, cases of sprue have been treated with vaccines made from
this organism.
An autolysate of the cultures is sterilized at 56°C. for an hour
and then centrifugalized. A one per cent. suspension of the
sediment is used for injection increasing from about 0.1 cc. to 1
cc. at weekly intervals. Five or six injections are given.
It is stated that the symptoms at the start of the treatment are
aggravated.
SECTION IV
HELMINTHIC INFECTIONS
CHAPTER XXI
ANCYLOSTOMIASIS
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—It is very probable that hookworm disease existed in
Egypt in the remote past and it has been claimed that a disease
mentioned in the Ebers Papyrus was of that nature.
Goeze found a hookworm in a badger in 1782. He named the parasite
_Ascaris criniformis_. Froelich, in 1789, found hookworms in
the fox and named them hookworms from the hook-like ribs of the
copulatory bursa. He proposed the generic name _Uncinaria_.
Therefore _Uncinaria_ belongs to the hookworms of the fox and is
not valid for any human species.
In 1838, Dubini noted that these worms were generally found in
very anaemic cases and that the mucosa of the duodenum or jejunum
frequently showed punctate haemorrhages. On account of the four
ventral teeth projecting from the mouth he gave it the name
_Agchylostoma_ or correctly _Ancylostoma_.
In 1854 Griesinger, as a result of frequently noting the lesions
produced by the worms, stated that they were the cause of Egyptian
chlorosis. In 1866, Wucherer connected hookworms with a disease
of Brazil called opilacao. In 1878 Grassi noted that the disease
could be diagnosed by the finding of the characteristic eggs in the
stools of patients.
It was the prevalence of a severe anaemia among the workmen employed
in the construction of the St. Gothard tunnel, which Perroncito
proved to be due to hookworm infection, that established the great
importance of this parasitic disease as the cause of a severe and
fatal anaemia (1879). About the same time it became generally
considered that the anaemias which affected workmen in mines were of
a similar nature.
That the disease was very prevalent in the Southern States of the
U. S., as long ago as 1849, is shown by the writings of Duncan,
who noted the frequency of anaemia, often associated with dirt
eating, among the slaves. He described the oedematous legs, the
protuberant belly and cardiac palpitation. There were several
cases reported in the U. S. from 1893-1897 but they were mainly in
foreigners.
From 1895 to 1901, Stiles kept insisting that hookworm disease
should be of frequent occurrence in the U. S.
A. J. Smith found several cases in persons living in Texas and
recognized the fact that these hookworms were different from
those of Europe. It was from a study of material from Smith and
Claytor in the U. S. and, later on, from Ashford in Porto Rico,
that Stiles, in 1902, reported a new genus of hookworm as existing
in man. It was first named _Uncinaria americana_ but _Uncinaria_,
belonging to the hookworm of the fox, was not valid, so he changed
the name to _Necator americanus_.
[Illustration: FIG. 88.—Geographical distribution of
Ancylostomiasis. Stars show where disease is widely prevalent.
Triangles, where less so.]
=Geographical Distribution.=—The disease is rare outside the
tropical and subtropical countries except in mines or tunnels where
suitable conditions of warmth and moisture exist.
It is extremely prevalent in India and Egypt as well as in China
and other parts of the East. It is a very important infection
in Porto Rico and the Philippine Islands. It is extensively
distributed in South America, especially Brazil, as well as in
Central America, Mexico and the Southern States of the U. S. The
inhabitants of many of the islands of the Pacific are heavily
infested. Hookworm disease is common in southern Europe.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—The hookworm infections of man come almost entirely
from two parasites, _Ancylostoma duodenale_, the Old World species,
and _Necator americanus_, which is generally called the New World
species from its having first been reported from the U. S. by Stiles.
Hookworms belong to the class Nematoda and family Strongylidae.
Quite recently Lane has reported a new species, _A. ceylanicum_, as
having been obtained from 3 men in Bengal, after treatment. This
species is the one that infects the civet cat in Ceylon. So far as
we know the other human species belong solely to man.
The male hookworms are a little more than ⅓ of an inch (9 mm.) long
and the females a little more than ½ inch (13 mm.) in length. The
males can readily be distinguished by their posterior, umbrella-like
expansion or copulatory bursa. The tail of the female is pointed.
The vulva of _A. duodenale_ is located in lower half of the ventral
surface; that of _N. americanus_ in upper half. The large, oval mouth
of the Old World hookworm has four claw-like teeth on the ventral
side of the buccal cavity and two knob-like teeth on the dorsal
aspect. It also has a pair of ventral lancets below the four ventral
teeth. One cannot make out a dorso-median tooth. In _N. americanus_
the buccal capsule is round, smaller and the ventral teeth are
replaced by chitinous plates. Dorsally there are two similar but
only slightly developed lips or plates. A very prominent, conical
dorso-median tooth projects into the buccal cavity. Through it
passes the duct of the dorsal oesophageal gland. There are also 4
buccal lancets. The copulatory bursa of the _Necator americanus_ is
also different, being terminally bipartite and deeply cleft in the
division of the dorsal ray, rather than tripartite and shallow, as
with _A. duodenale_.
The anterior extremity of _Ancylostoma_ bends in the same direction
as the general body curve while that of _Necator_ hooks back in an
opposite direction to the body curve.
By dropping the worms, while still alive, into hot 70% alcohol they
readily assume the attitudes noted above.
In general, _Ancylostoma_ is larger and thicker than _Necator_.
The name hookworm was given to these nematodes from the hook-like
processes of the ribs of the rays of the copulatory bursa.
Dubini called the Old World parasite _Agchylostoma_, properly
_Ancylostoma_, on account of the 4 formidable hook- or claw-like
ventral teeth of the buccal capsule. (αγχὶλος, hook, and στομα,
mouth.)
_A. ceylanicum_ is somewhat smaller than _A. duodenale_ and in the
copulatory bursa of the male we have a deeper cleft in the dorsal
ray and 2 rather long tips to each branch instead of the shallow
cleft and 3 stumpy processes of the 2 branches as in _A. duodenale_.
=Life History.=—The delicate-shelled eggs pass out in the faeces,
and in one or two days a rhabditiform embryo (200 × 14 microns) is
produced. The mouth cavity of the embryo is about as deep as the
diameter of the embryo at the posterior end of the mouth cavity; that
of _Strongyloides_ is only about one-half as deep as the diameter.
[Illustration: FIG. 89.—1a, Copulatory bursa of _Necator
americanus_, showing the deep cleft dividing the branches of the
dorsal ray and the bipartite tips of the branches; also showing the
fusion of the spicules to terminate in a single barb. Scale 1/10
mm. 1b, Branches of dorsal ray magnified. 2a, The buccal capsule of
_N. americanus_. 2b, The same magnified. 3a, Copulatory bursa of
_Ancylostoma duodenale_, showing shallow clefts between branches of
the dorsal ray and the tridigitate termination. Spicules hair-like.
3b, The dorsal ray magnified. 4a, The buccal capsule of _A.
duodenale_, showing the much larger mouth opening and the prominent
hook-like ventral teeth. 4b, The same magnified. 5a, Egg of _N.
americanus_. 5b, Egg of _A. duodenale_. 6a, Rhabditiform larva of
_Strongyloides_ as seen in fresh faeces. 6b, Rhabditiform larva of
hookworm in faeces eight to twelve hours after passage of stool. From
Stitt.]
As a practical point, the anaerobic conditions in the intestines
seem to prevent development of the hookworm ova or at any rate
the absence of the oxygen, so necessary for the segmentations
preliminary to the formation of the embryo, prevents it. Therefore
hookworm ova in freshly passed faeces never show other than
commencing segmentation while development of the larvae of
_Strongyloides_ takes place in the intestines, so that in freshly
passed faeces we find, generally, actively moving larvae or at
least eggs containing fully developed embryos. Hookworm ova very
rarely show more than 4 segments or exceptionally 8 segments in the
freshly passed egg.
In the presence of oxygen these ova rapidly develop into larvae,
particularly at a temperature of about 27°C. Beyond 37°C. and below
14°C. development does not seem to take place.
The rhabditiform larvae grow rapidly and by the 3rd day are about
300 microns long and undergo a primary moulting. By the 5th day
the bulb-like swellings disappear and the larva becomes possessed
of a straight oesophagus, thereby becoming a strongyloid larva. It
then undergoes a 2nd ecdysis or moulting, but instead of casting
off this old covering, it retains it as a protecting sheath. The
full grown larva is about 550 by 24 microns. At this time it ceases
to take food but can move actively in its sheath so that it can
crawl up blades of grass or vertical sides of mines. They can live
in this state for months, when moisture and shade are present, but
are rapidly killed by drying. Before becoming encysted hookworm
larvae are readily destroyed by the action of the sun or chemicals
or even by dilution of the faeces, especially with urine. Cort and
others have found it a common occurrence for mature larvae to lose
their sheaths while living in the soil, and to continue their lives
in the unsheathed state. The proportion losing their sheaths varies
from 52 to 98%.
This is the _infecting stage_ in which the larvae bore their way into
the skin, which is the usual method of infection, or, occasionally,
by entering the mouth on vegetables or otherwise.
Looss thought that they entered the skin by way of the hair
follicles but the idea now is that they can bore into any part of
the skin. It only requires a few minutes for the larvae to enter
the skin. From the subcutaneous tissues they effect an entrance
into lymphatics or veins, go to the right heart, thence to lungs.
From the alveolar capillaries they pass into the pulmonary alveoli,
thence up the bronchi and trachea, to pass out of the larynx and
then down the oesophagus to the stomach. The larva loses its
protecting sheath in the stomach and in a few days develops a
provisional buccal capsule.
By the end of the 2nd week, after another ecdysis, the larvae
have grown to be about 2 mm. long and 130 microns broad and in
about 4 weeks become adults, usually in the jejunum, where, after
fertilization of the females by the males, the giving off of
eggs begins. The adults attach themselves to the mucosa of the
intestine, feeding on the deeper structures of the mucosa, or on
the tissues of the submucosa. Sambon believes that the larvae can
work their way into the jejunum without going there by way of the
trachea and oesophagus.
By providing an exit to the trachea, Fülleborn demonstrated that
in dogs, infected with the dog hookworm, great numbers of larvae
poured out of the trachea. In other dogs he stitched the oesophagus
to the skin and noted larvae coming out of these openings. In these
dogs, with the ordinary channel obstructed, infection did occur
with, however, only a few worms, thus showing the truth of Sambon’s
views but at the same time demonstrating the unimportance of such a
route of infection.
The mouth cavity of the embryo is about as deep as the diameter
of the embryo at the posterior end of the mouth cavity, that of
_Strongyloides_ is only about one-half as deep as the diameter.
The genital anlage of _Strongyloides_ is much larger than that of
_Ancylostoma_.
=Epidemiology.=—When faeces containing hookworm eggs are deposited
where conditions of moisture, warmth and shade exist, they develop
into the infecting stage, which is the nonfeeding but motile larva
inside the cuticle formed by the second moulting. While eggs and
younger larvae are killed rapidly, the encysted larvae withstand
drying for considerable periods.
[Illustration: FIG. 90.—_Ancylostoma duodenale_ (life size). Shows
some worms adherent to the intestinal mucosa and some free. (From
Jefferys and Maxwell.)]
Stiles notes that the more favorable conditions for development are
in a porous, sandy soil rather than in a clay one. Where a sewerage
system exists there is very little danger of the spread of hookworm
disease and the same is true where there is proper disposal of the
faeces by burning, boiling or treatment in a septic tank. In rural
districts, however, where the stool is often deposited in the shade
and retirement of a clump of trees, the soil becomes infested with
myriads of larvae, so that one standing with bare feet on such a
spot easily becomes infected. It is for this reason that shoes are
of protective value. In infected mines with temperatures below
22°C. infection is rare (6%); from 22°C. to 25°C. more common
(16.6%), and above 25°C., it may reach high figures (61%).
Those of the negro race do not suffer from the infection as do the
whites. They appear to have an immunity but serve as carriers of
the disease. There is difference of opinion as to the length of
time the parasites may live in man in the absence of reinfection.
Some consider this period one of a few months, others of two or
three years. We can certainly consider that a case leaving an
infested region will get rid of his parasites within seven years.
PATHOLOGY
The site of entrance of the larvae is characterized by a dermatitis
which is often called “ground itch” or “foot itch” by reason of
its frequent location in the foot which has come in contact with
the faeces-polluted soil. The dermatitis disappears in about two
weeks unless some secondary infection occurs. There are reports of
pulmonary irritation which may be explained by the wandering of the
larvae through the lungs.
[Illustration: FIG. 91.—Longitudinal section through a hookworm
attached to the intestinal mucosa, about 6 hours after the death of
the carrier. A portion of the submucous coat is drawn into the buccal
cavity and trails along cord-like into the oesophagus, in which 4
small tissue nuclei are still discernible. Section 0.01 mm. thick.
(From Mense.)]
Pronounced anaemia with yellow, wax-like skin is a feature of
severe cases but emaciation is rare, the subcutaneous fat still
remaining. There is frequently oedema about the ankles. In the
jejunum we find small haemorrhagic spots from the size of a pea
to that of a half dollar. A worm may be found in the center of
this spot. In sections from the tissues injured by the bite we
note an infiltration of eosinophiles. The heart often shows fatty
degeneration with dilatation. The liver and kidneys usually show
fatty change while the spleen is generally shrunken. Sandwith noted
splenic enlargement in many of his autopsies but such enlargement
must have been due to other causes.
There are many views as to the manner in which the damage due to the
hookworm is brought about. Some think it by bacterial infections
occurring through the wounds made by the worms, others that it is due
to a haemolytic toxic material excreted by the worms, while Stiles
considers the ingestion of the patient’s blood important. Looss
thinks it due to the gradual destruction of the intestinal mucosa
from the feeding on this, and especially of the submucosa, by the
worms. In their feeding the worms move from site to site. When they
leave a point bleeding continues and this may account for much of the
anaemia.
On the side of the blood we have at first a moderate leucocytosis
which disappears with the anaemia. Eosinophilia and Hb. percentage
reduction are often observed. In 3 cases I have known a fatal
pernicious anaemia to develop.
SYMPTOMATOLOGY
In a secondary anaemia, with early and marked cardiac palpitation
together with epigastric tenderness and a tendency to mental
retardation and physical deterioration, one should always examine the
stools for hookworm eggs.
The course of the disease is decidedly insidious and indefinite
and the clinical diagnosis notoriously uncertain, as shown by many
reports where physicians of experience, after examining a number
of persons in a mill or school and only diagnosing 2 or 3% as
infected, have been astonished, upon examination of the faeces of
the group, to obtain positive evidence of infection in 70 to 80% of
the number examined.
For convenience, it is well to divide hookworm cases into 3 groups;
1. Where the person infected fails to show any special evidence of
abnormality, the diagnosis resting almost entirely on the finding of
ova in the faeces.
Such cases may show very slight reduction in haemoglobin and
only admit of a certain lack of energy. The best indication that
hookworm infection is doing the host injury is that after treatment
they gain in weight and energy and show improvement in mental
concentration.
2. Mild cases with moderate degrees of anaemia, the Hb. percentage
ranging from 55 to 75. In these cases there is rather marked
epigastric tenderness with frequent attacks of acid eructations.
Cardiac palpitation and a tendency to shortness of breath may be
quite noticeable. Headache and vertigo may be present.
3. Severe cases. In such cases we may find extreme anaemia with Hb.
percentages around 35 or even as low as 15. I have always felt that
one was only approximating when recording percentages of 10 or lower.
These cases are very weak and show marked cardiac palpitation and
dyspnoea upon the slightest exertion. There is often dilatation of
the stomach and a protuberant abdomen. The red cells may fall below
1,000,000. There is also oedema, especially about the feet and
ankles. Tinnitus aurium is rather frequent.
Such cases often show depravity of appetite, the best-known craving
being that for earth. Other patients crave chalk, wood, cotton, etc.
[Illustration: FIG. 92.—Fatal case of ancylostomiasis. Red cells
810,000. Hb. 15%. White count 6400. Eosinophiles absent. Upper part
of small intestines lined with hookworms. (From U. S. Naval Medical
Bulletin.)]
It is in children that we have the most serious effects of
the disease, there being marked stunting of the growth with a
corresponding mental backwardness. Such children show marked
retardation and delay in answering the question asked them and
often repeat it in a drawling manner. Tested by the Binet-Simon
method we may find a sixteen year old child to have the mental
development of a ten year old one, but at the same time we would
note that from a standpoint of physical development the child only
seemed ten years old.
As the child approaches adult age we note a striking lack of sexual
development and the lack of pubic hair. In girls there is delay in
the onset of the menstrual periods or these may never appear.
In from 80 to 90% of cases there is a history of dermatitis,
particularly of toes or feet, which is commonly called “ground itch,”
“foot itch,” or “dew itch.” This is most frequent between the toes
or on the inner side of the sole of the foot. The irritation is
due to the penetration into the cutaneous tissues of the hookworm
larvae. The itching is intense and secondary infections often occur
as the result of scratching. Vesicles appear about the second day and
are often ruptured by the scratching with a resulting pustular or
impetiginous conditions. The skin and hair generally are dry.
As a rule the temperature is normal throughout the course of an
uncomplicated case of hookworm disease. During the first week or so
following a heavy infection there may be pulmonary manifestations
when the larvae are migrating by way of the lungs.
In the diagnosis of a case Stiles attaches much importance to a
tallow-yellow color of the alae of the nose and the forehead, as well
as to the eye characteristics which are like those seen in the eye of
a fish or that of an intoxicated person.
He also notes that the pupil tends to dilate instead of to contract
when the patient looks at a bright light. It has seemed to me that
the condition is rather one of hippus. In severe cases retinal
haemorrhages may occur. There may be night blindness. Ascites may
be present in advanced cases.
Symptoms in Detail
_Skin Manifestations._—The dermatitis following the penetration of
the larvae is most often about the toes or inner side of the sole
of the foot. The skin is very dry and often a pale earthy color.
A tallow-yellow tinting of the alae of the nose may be observed.
The hair is dry and scanty or absent in pubic and beard regions.
Oedema, especially of ankles or feet, is common.
_Circulatory and Respiratory Systems._—Palpitation of the heart is
early and marked. Functional murmurs are frequent in the advanced
stages. Pulsation of the neck veins is also common. The pulse
rate averages about 110 and the blood pressure is low. There is
frequently some right side dilatation of the heart. A high pulse
pressure is common in severe cases. Shortness of breath on slight
exertion is the most common respiratory symptom. There are at times
cough and bronchitis, probably induced by the irritation of the
larvae in the pulmonary alveoli.
_Digestive System._—Epigastric tenderness going to the right
is very characteristic. The stomach is often dilated and the
gastric juice hyperacid. As the anaemia increases the acidity
diminishes. It has been suggested that the desire to neutralize
this acidity with an alkali is the explanation of the desire for
alkali-containing earth on the part of “dirt eaters.”
Patients often are pot-bellied. Constipation is rather a common
feature and the stools very rarely show macroscopic blood.
_Nervous System._—Hookworm patients are not only physically
tired but, as well, mentally tired. The infection in children
leads to a backward mental state. Patients have very little
energy or initiative and are often considered stupid and lazy.
Hypochondriasis is at times noted and some severe cases become
melancholic.
_The Blood._—The red cell count averages in marked cases 2,500,000
to 3,000,000 red cells per cu. mm. The Hb. percentage is down in
such cases to between 30 and 50. The color index is well below
1, except in certain rare cases, when the color index is that of
pernicious anaemia, being above 1. These latter cases are very
resistant to treatment and often show very few infecting worms
notwithstanding the severity of the symptoms.
There is at times a moderate leucocytosis but as a rule the white
count is approximately normal.
Eosinophilia is quite characteristic and usually ranges from 15 to
35% of the leucocytes. Eosinophilia tends to disappear as the cases
become advanced.
The spleen and liver very rarely give rise to any symptoms and
while albuminuria is rather common in advanced cases with oedema
about the feet, yet casts are but rarely found.
DIAGNOSIS
=Clinical Diagnosis.=—The diseases with which it is most likely to
be confused are beriberi, chronic nephritis and malarial cachexia.
Stiles notes that heavy _Ascaris_ infections may give rather similar
symptoms.
The signs of a multiple neuritis should differentiate beriberi, and
the presence of casts or high blood pressure, chronic nephritis.
Recently, there has been a great deal written about the danger of
confusing hookworm disease and malarial cachexia, the statement
being often made that splenic enlargement is a feature of
ancylostomiasis. Most authorities, however, state that the spleen
of ancylostomiasis is not enlarged, this point being of diagnostic
value in differentiating it from malaria and kala-azar.
=Laboratory Diagnosis.=—As a matter of fact the diagnosis is almost
invariably made by finding hookworm ova in the faeces. The eggs are
oval and thin-shelled with a wide, clear, glassy zone separating the
more or less segmented, granular central portion from the shell.
Formed stools are more satisfactory for examination than the
liquid ones resulting from a dose of salts. Put about 2 drops of
water or 1% trikresol solution in the centre of a glass slide and
emulsify in it as much of the faeces as is held by the spatulate
end of a wooden toothpick. A small piece of wood or a match stick
will answer. These preparations can be readily examined without a
cover-glass, using a ⅔ inch objective, with a 1-inch ocular.
Cultural methods give a higher percentage of success than looking
for ova in the stools. Put a pile of 2 inch filter papers in the
center of a Petri dish. Fill the dish with water to the level of
the paper island. Smear a thick layer of faeces on the paper. The
larvae hatch out and can be found by centrifuging the water.
It is usually stated that about 500 worms must be present for
several months to produce symptoms. Grassi has thought that the
presence of 150 eggs in 0.01 gm. faeces indicates the presence of
1,000 worms, of which 25% would be males.
There may be as many as 4,000,000 eggs in a stool. Bass has
proposed the following method for the examination of faeces for
ova: The faeces, which have been made fluid, should be centrifuged
and the supernatant fluid containing vegetable débris poured off.
The sediment contains hookworm eggs. Then pour on sediment a
calcium chloride solution of sp. gr. 1.050. Again centrifuge and
decant. Next add calcium chloride solution of a sp. gr. of 1.250
and centrifuge. This brings to the surface the hookworm eggs which
may be pipetted off. As a rule, the finding of hookworm eggs is
very easy without such a technique.
[Illustration: FIG. 93.—Ovum of _Ancylostoma duodenale_. By J. A.
Thomson. (Jefferys and Maxwell.)]
Recently we have been using Barber’s technique. Emulsify the faeces
in equal parts of glycerine and saturated salt solution on a slide.
The eggs rise to the surface and are easily discovered with the
⅔-inch objective. As a centrifuge method, Barber emulsifies faeces
in this same mixture which brings the eggs to the surface. A wisp
of cotton is placed on the surface and 3 or 4 drops of melted
agar dropped on the cotton. The disc of agar is removed with the
cotton, deposited on a slide and examined for entangled eggs. With
operculated eggs this method does not seem to be satisfactory as
the salt solution loosens the operculum and floods the contents
of the shell,—thus altering the specific gravity of the egg and
preventing flotation.
_Lane Levitation Method._—Clayton Lane recommends a technique
which he designates as the levitation method. In this procedure the
concentrated sediment of a centrifuged specimen is transferred to a
glass slide, where it is mixed with one cc. of water. The slide is
allowed to stand for five minutes and is then immersed in water and
manipulated until all coarse matter has floated free. The hookworm
ova stick firmly to the slide and are not washed away. Lane reports
that on an average this method results in a ten-fold concentration
of ova.
In certain cases, where a microscope is not available, the
diagnosis may be made by finding the worms in the stool following a
thymol treatment.
Whyte has recommended the phenolphthalein test for occult blood as
of value in determining the cure of ancylostomiasis. This test is
so delicate that the least trace of blood from the mucosal lesion
will be detected.
The presence of eosinophilia is of great assistance in diagnosis but
it should be remembered that not rarely severe cases of the disease
fail to show any excess of eosinophiles.
Charcot-Leyden crystals are often present in hookworm stools.
PROGNOSIS
The disease is more serious in children than in adults, on account of
its interfering with physical and mental development. The dark races
do not seem to suffer as much as the white ones. Treatment is usually
most successful, but in those who are debilitated by other diseases
or, in those in whom the disease has assumed a pernicious anaemia
tendency, the outlook is not good.
The presence of eosinophilia is of good prognostic significance
as the absence of eosinophiles indicates an exhaustion of the
haemopoietic system.
The disease shortens the life of the people in an infected district
and makes them readily fall victims to intercurrent diseases.
Various statistics give the mortality as from less than one-half of
1% to figures approximating 7%.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—The first measure is to diagnose infections in
carriers and to insist upon the treatment of such persons. The
proper disposal of the fecal material from hookworm patients is the
objective point in prophylaxis.
The use of some type of properly constructed privy is essential as
there is nothing more favorable to the development of the hookworm
larvae from eggs to infecting stage than the practice of defecating
on the ground where conditions of porous, sandy soil, shade and
moisture exist. Later on, such a spot teems with infecting larvae
and the person stepping there with bare feet is almost sure to
become infected. For this reason the wearing of shoes is an
important prophylactic measure. At the same time shoes are not a
sure protection, as Ashford has noted infections in soldiers who
wore good shoes. The fecal material, collected in a pail or tub,
should preferably be burned or boiled. Otherwise it should be
buried not less than 300 feet from the water supply and down hill
from the same.
The best method is to use some septic tank process as the anaerobic
processes of fermentation destroy the eggs.
The use of an amount of compound cresol solution equaling the fecal
mass, plus urine, is of value.
Hookworm disease tends to disappear in towns or cities where there
is an efficient sewerage system.
Hookworm disease is one of the most conspicuous examples of soil
pollution disease.
Some authors think _Ancylostoma_ more difficult to expel than
_Necator_.
=Treatment.=—The drugs best known in treatment are thymol and
chenopodium but carbon tetrachloride offers the greatest promise.
_The Thymol Treatment._—Bozzolo introduced this drug in the
treatment of hookworm disease in 1879. Thymol has an aromatic,
thyme-like odor and a pungent taste and, while soluble in about an
equal amount of alcohol, is only soluble in water in the proportion
of 1 to 1100.
It is usual to prescribe the drug in 5-grain capsules or preferably
in cachets, one part of thymol being triturated with an equal
amount of sugar of milk. If the cachet is moistened with a little
water it may be swallowed like a raw oyster.
Stiles prefers giving the treatment on Sunday so that the working
days of the patient may not be lessened. By giving the patient
bicarbonate of soda for a few days before the treatment it is
thought that the mucus lining of the jejunum is cleared away so
that the worms are more readily affected by the drug. At any rate
one should give about 1 or 2 ounces of a 50% solution of Epsom
salts on Saturday evening. Sodium sulphate is preferred by some.
The following morning at 6 A.M. the patient takes one-half the dose
of thymol proper for his age and at 8 A.M. he takes the remaining
half of the dose. At 10 A.M. he takes another dose of Epsom
salts. The reason for dividing the dose of thymol is that should
untoward symptoms occur after the first portion of the dose we do
not give the second. Stiles now prefers to divide his dose into
three portions, one to be given at 6 A.M., one at 7 A.M. and the
remaining third portion at 8 A.M., followed by salts at 10 A.M. The
patient should lie on the right side while taking the treatment to
facilitate the passage of the drug from the often dilated stomach.
The patient should remain in bed until 12 o’clock when he may take
some coffee, without milk, and crackers.
Patients must be warned to avoid anything containing fats or alcohol
while undergoing treatment as fats and alcohol dissolve the thymol
and tend to cause poisoning. Under no circumstances should castor oil
be used. People are apt to forget that butter, milk, etc., contain
the dangerous fats.
Seidell has shown that about one-third of the thymol dosage is
excreted in the urine and very little by faeces. This shows
absorption of the drug. It is thought some of the drug may be
excreted by the lungs. Congestion of the lungs has been reported in
fatal cases of thymol poisoning.
Mild symptoms of poisoning are burning in the pit of the stomach
and tingling sensations of the body. More severe symptoms are
those associated with cardiac weakness and respiratory distress.
Coffee and strychnine are the usual remedies for thymol poisoning.
Inhalation, but not swallowing, of aromatic spirits of ammonia is
often of value.
The thymol dosage recommended according to the age, or rather the
apparent age of the patient, is:
Under 5 years old 7½ grains.
From 5 to 9 years old 15 grains.
From 10 to 14 years old 30 grains.
From 15 to 19 years old 45 grains.
From 20 to 59 years old 60 grains.
Above 60 years old 30 to 45 grains.
Total dose to be divided into 2 or 3 portions. The patient is
allowed to eat only a light luncheon and supper the day of the
treatment but the next day he may resume his regular meals.
As a rule most of the worms expelled by the treatment will
have been passed by night of the day of treatment, although an
occasional one may be passed for four or five days.
In from 25 to 50% of cases all the worms may be expelled in
one treatment but it is usually necessary to give as many as 3
treatments, one on each of three Sundays.
_Thymol and Beta-naphthol._—Nicol in a comparison of the efficacy
of various drugs, noted that thymol in 90-grain doses, taken in
3 portions of 30 grains each, at 6, 8, and 10 A.M. expelled 98%
of the worms at the first treatment and the remaining worms at
the second treatment a week later. With this rather large dose he
frequently observed a tendency to syncope. He used Epsom salts as a
purgative.
On the other hand, while using 60 grains of beta-naphthol, given in
two portions at 6 and 8 A.M., followed by salts, 86% of the worms
were expelled at the first treatment and 14% with the second one.
He did not observe any bad effects from beta-naphthol.
The great objection to beta-naphthol is that it is a renal irritant
and may damage a kidney already diseased.
Nicol found the treatment with eucalyptus oil, 2 cc., chloroform,
3 cc. and castor oil, 30 cc. vastly inferior in anthelminthic
effect to the other two treatments and liable to cause severe
manifestations of nausea and syncope.
It is better to divide the dose as just stated into two portions,
the second half to be given about one-half hour after the first
portion. This reduces the danger from the chloroform.
Schüffner tried male fern and only obtained 7 hookworms while the
next day, using thymol, 1253 hookworms were expelled. He notes that
thymol is dangerous when administered to patients with acute or
subacute dysentery.
In Brazil a tabloid of 5 grains beta-naphthol combined with 1
grain of phenolphthalein has been generally employed. Using
phenolphthalein in this way enables them to dispense with purgation.
_Oil of Chenopodium Treatment._—As the result of comparing
the relative efficiency of thymol and oil of chenopodium the
International Health Board Commission reported in favor of oil of
chenopodium. In only 7.6% of the cases treated with chenopodium was
there failure to eradicate the parasites while there was noted 23.6%
of failures with thymol. The dose of oil of chenopodium recommended
was 1.5 cc. given in three divided doses of O.5 cc. at 7, 8, and 9
o’clock in the morning. Two such treatments will remove 99% of worms
present in a case. The Commission found the oil more efficient than
an emulsion of the oil.
The low diet and preliminary dose of salts, as noted under thymol
treatment, are to be recommended although the commission found
various purges to have little effect on the results of treatment.
At 11 o’clock give a purgative dose of magnesium sulphate.
The maximum dose of oil of chenopodium is usually given as 3 cc.
but a number of deaths have followed the administration of doses of
from 2 to 3 cc., so that it is better to keep within 1.5 cc.
After effects of treatment, such as dizziness, depression, unsteady
gait, partial loss of consciousness, tingling of hands and feet,
burning sensation in the epigastric region and nausea are more
frequent with chenopodium than following thymol. The toxic symptoms
may be greatly delayed and even be postponed for a day or so. A
large dose of castor oil seems to be the most important measure
in treating a case of chenopodium poisoning. The same methods of
stimulation as noted under thymol poisoning are also indicated.
Kantor has treated a large number of cases with oil of chenopodium
administered through the duodenal tube. After the bucket had passed
the pylorus he introduced into the duodenum about 2 cc. of oil of
chenopodium and followed this in six minutes with two (2) ounces
of a warm saturated solution of magnesium sulphate. The tube is
withdrawn after introducing the salts. Several copious watery
stools follow in a short time.
_Carbon tetrachloride_ in a dose of 3 cc. administered in hard
gelatine capsules, is recommended by Hall for the removal of
hookworms and ascarids. The drug is cheaper, more effective, and,
when chemically pure, safer than thymol or chenopodium. It does
not depress unstriated musculature or lessen peristalsis, thus
eliminating the use of purgatives, which is an item of expense in
extensive hookworm campaigns. The drug is of no value in treatment
of tapeworms and is as unreliable as other anthelminthics for the
removal of whip-worms.
There is a rapidly growing mass of reports concerning the clinical
use of carbon tetrachloride, all of which agree in confirming
experimental observations regarding its effectiveness, and indicate
that a standard dosage as high as 10 to 12 cc. may be safely employed.
After expelling the worms it is advisable to give the patient a
tonic containing iron or arsenic. In those cases with a tendency to
pernicious anaemia the arsenic treatment is better than that with
iron.
In the treatment of ground itch the usual application is a zinc
oxide ointment containing 10 grains of salicylic acid to the ounce.
Barlow recommends a 3% salicylic acid solution in alcohol.
CHAPTER XXII
FILARIAL INFECTIONS
GENERAL CONSIDERATIONS
The filarial worms are thread-like nematodes, with a thin cylindrical
oesophagus, which live in various parts of the body and may or may
not give rise to disease conditions. It is one of the most remarkable
facts in animal parasitology that a person may harbor numerous adult
filariae and myriads of embryos without in any way manifesting
symptoms of the infection. In most of the filarial worms the female
has a double uterus with the uterine opening near the anterior
extremity.
[Illustration: FIG. 94.—Geographical distribution of Filariasis.]
It has been proposed to designate the filarial embryo by the
term microfilaria, reserving the generic name _Filaria_ for the
adult parasite. This may be convenient for differentiation but
zoölogical nomenclature does not permit different names for adults
and embryos. While there have been almost 20 different filarial
species reported for man there is, in some instances, doubt as to
the correctness of the observation, and again, a well recognized
species has at times been considered as a new species and given a
new name.
From a practical standpoint we need only consider: (1) _Filaria
bancrofti_; the adult of which lives in the lymphatic glands and
vessels while the sheathed embryos (which from their appearance in
the blood only at night are called _Filaria nocturna_) obtain access
to the peripheral blood vessels.
[Illustration: FIG. 95.—1a, Adult female Guinea worm (_Dracunculus
medinensis_) showing anchoring hook at posterior extremity. 1b,
Cross section of female _Dracunculus_ showing uterus filled with
embryos. 1c, Striated embryos of the Guinea worm. 1d, _Cyclops
coronatus_, the minute crustacean which serves as the intermediate
host of _D. medinensis_. 2a-2d, Anterior and posterior extremities
of _L. loa_. 2c, Section showing tuberculated cuticle. 2b, Male
and female _L. loa_, natural size. 3a, Bulbous anterior extremity,
_Filaria bancrofti_. 3b, Tail of male. 3c, Tail of female. 3d, Male
and female, natural size of _F. bancrofti_. 4a, Tumor mass of _O.
volvulus_ laid open. 5, Mosquito showing filarial embryos in thoracic
muscles (a) and in labium (b). The labella which are separated from
the labium by Dutton’s membrane are seen at (c). 6(a) Embryo of _F.
bancrofti_. (b) Embryo of _L. loa_ showing filling of tail end with
cells. 7, Microfilaria of _F. bancrofti_ in blood. Dotted lines show
location of break in cell column and V spot.]
Various well-known conditions are caused by this parasite, such as
elephantiasis, varicose groin glands, chyluria, etc. This infection
was formerly stated to be caused by _Filaria sanguinis hominis_.
(2) _Loa loa_, the adult of which wanders about in the subcutaneous
tissues, characteristically in the region of the eyes, while the
sheathed embryo is found in the blood during the day, hence _Filaria
diurna_.
Calabar swellings, irregular febrile conditions and the
disagreeable sensations incident to the wanderings of the worm are
clinical features of this infection.
-----------+--------------------+--------------------+-------------------
| Adults | Embryos | Remarks
-----------+--------------------+--------------------+-------------------
|Male 40 by 0.1 mm. |Sheathed, 300 by 7.5|Transmitted by
| Female 90 by 0.28 | microns. Distance | mosquitoes, Culex
| mm. Smooth cuticle.| from head to V spot| fatigans and
Filaria | Bulbous anterior | 90 microns; to | Stegomyia pseudo-
bancrofti | extremity. | break in cells 50 | scutellaris.
| Occupy lymphatic | microns. Tail | Causes
| glands and vessels.| rather straight. | elephantiasis,
| | Terminal cells do | lymph scrotum,
| | not fill up tail | chyluria, etc.
| | end. Nocturnal |
| | periodicity in |
| | peripheral |
| | circulation. |
-----------+--------------------+--------------------+-------------------
|Male 27 by 0.3 mm. |Sheathed, 240 × 7 |Transmitted by
| Female 55 by 0.4 | microns. Distance |species of a biting
| mm. Cuticle tuber- | from head to V spot| fly—Chrysops.
| culated. Anterior | 65 microns; to | Causes calabar
Loa loa | extremity like | break in cells | swellings. Worms
| truncated cone. | 40 microns. Cork- | often visit ocular
| Wanders in | screw tail which is| region.
| subcutaneous | completely filled |
| tissues. | up with terminal |
| | cells. Diurnal |
| | periodicity in |
| | peripheral |
| | circulation. |
-----------+--------------------+--------------------+-------------------
|Male 40 by 0.07 mm. |Without sheaths, 200|Transmitting agent
| Female 75 by 0.1 | by 5 microns. Post-| not surely known.
| mm. Cuticle smooth.| erior two-thirds | Mosquitoes and
Acanthoch- | Tip of tail shows 2| tapers to blunt | ticks suggested.
eilonema | triangular | ending. Distance | No pathogenicity.
perstans | processes. Found | from head to V spot|
| about root of | 49 microns; to |
| mesentery. | break in cells 34 |
| | microns. Persists |
| | in circulation both|
| | day and night. |
-----------+--------------------+--------------------+-------------------
|Male 30 by 0.14 mm. |Without sheaths, 250|Method of trans-
| Female usually | by 7.5 microns. | mission unknown.
Onchocerca | fragmented. | Found in cyst-like | Causes small
volvulus | Possibly 75 by 0.36| spaces of tumors. | cystic tumors,
| mm. Cuticle | Not in peripheral | under skin of
| striated. Found | circulation. | thorax
| coiled up in | | especially.
| cyst-like tumors | |
| under skin. | |
-----------+--------------------+--------------------+-------------------
|Male from Leiper’s |Without sheaths. 600|Embryos swallowed
| monkey 22 mm. | × 20 microns. Long | by Cyclops. Man
| Female 80 to 90 cm.| slender tail. | drinks water
| long by 1.6 mm. | Cuticle striated. | containing
Dracunculus| wide. Smooth white | Extruded from break| Cyclops.
medinensis| body. Anchoring | in skin of patient.|
| hook at tail end. | |
| Female lives in | |
| subcutaneous | |
| tissue of lower | |
| extremity. | |
-----------+--------------------+--------------------+-------------------
(3) _Onchocerca volvulus._ The males and females of this parasite
are found coiled up in channeled connective tissue tumors of the
subcutaneous tissues.
The sheathless embryos have been surely found only within these
tumors and not in the blood.
(4) _Acanthocheilonema perstans._ This parasite does not seem to give
rise to clinical manifestations except possibly to cause an irregular
fever.
The adult is found in the retroperitoneal connective tissue or fat,
while the sheathless, blunt-tailed embryo is found in the blood,
both by day and night, hence _perstans_. The adult forms are found
in the tissues behind the abdominal aorta and at the attachment of
the mesentery.
(5) _Dracunculus medinensis._ The female of this parasite, about 36
inches long and 1/15 inch in diameter, travels to the subcutaneous
tissues of the extremities and boring through the skin causes a small
surface erosion.
An unimportant filarial worm which has been found only in the West
Indies and British Guiana is known as _Filaria demarquayi_ or _F.
ozzardi_. The embryos have sharp tails and are without a sheath.
The parasite is not known to produce symptoms.
HISTORY
_Filaria bancrofti._—While elephantiasis was frequently described by
ancient writers yet the confusion between Elephantiasis Graecorum, a
term applied to leprosy, and Elephantiasis Arabum, or the filarial
condition, made the question of the nature of the skin thickenings
very indefinite.
The thickenings due to leprosy and those connected with filariasis
were separated clinically by observers during the 17th and 18th
centuries, Hilary, in 1750, having accurately described the
progress of that form of elephantiasis connected with elephantoid
fever and lymphangitis. In 1863 Demarquay discovered filarial
embryos in the exudate of a chylous hydrocele and three years
later Wucherer, in Brazil, found similar nematode larvae in the
urine of a case of haematochyluria. Commencing with the year 1863
Lewis carried on a series of investigations in Calcutta in which
he found these embryos not only in the urine of patients with
chyluria but as well in the lymph and blood of those affected with
elephantiasis. He called the parasite _Filaria sanguinis hominis_,
a name still frequently employed by medical writers.
In 1876 Bancroft, in Australia, discovered the adult filarial worms
in a lymphatic abscess, hence the name _Filaria bancrofti_. In
1878 Manson, in China, demonstrated the mosquito transmission of
the disease as well as the phenomenon of nocturnal periodicity.
Manson’s idea, however, was that the fully developed embryo escaped
from the body of the infected mosquito at the time of the death of
the insect and that man contracted the infection in drinking water.
The investigations of Low and more recently those of Fülleborn and
Bahr and others have shown that the larvae escape by way of the
mosquito’s proboscis and enter the skin of man.
_Loa loa._—The knowledge of a filarial infection of the region of
the eye seems to date from the time of Magellan. Although the disease
is now confined to the west coast of Africa, cases were reported from
the West Indies by Mongin and Bajou during the 18th century. These
cases were in slaves who had contracted the infection in Africa.
[Illustration: FIG. 96.—Section of _Stegomyia pseudoscutellaris_,
showing filariae in thorax on tenth day of development, travelling
forwards into proboscis. By permission from Manson’s Tropical
Diseases.]
In 1891 Manson noted the presence of the larval forms which showed
a diurnal periodicity in the peripheral blood.
_Dracunculus medinensis._—Ancient Egyptian writings would indicate
that the disease was well known in those times. It is believed that
the fiery serpent of the wilderness, which afflicted the Children of
Israel, was an infection of this sort.
The prevalence of dracontiasis, as the infection is generally
termed, in Arabia, was well known to the Greeks and Romans.
Fedschenko, in 1870, noted the transmission of the disease by
species of _Cyclops_.
_Onchocerca volvulus_ was first discovered in 1893, in peculiar
tumors of the natives of the Gold Coast.
[Illustration: FIG. 97.—Female guinea worm (_Dracunculus
medinensis_) lying under the skin of the forearm. By permission from
Manson’s Tropical Diseases.]
_Acanthocheilonema perstans_ was first found by Manson, in 1891, in
the blood of natives of the Congo.
Daniels also found these embryos, along with those of _F.
demarquayi_, in the blood of natives of British Guiana.
FILARIA BANCROFTI
GEOGRAPHICAL DISTRIBUTION
This parasite has been found in almost all tropical and subtropical
countries. It is quite prevalent in the West Indies and has been
found in some of the Southern states of the U. S. It is very common
in some of the South American countries as well as in Central
America. The infection is widespread in Arabia, India and China.
Africa, especially the West Coast, and Australia, particularly in
Queensland, are parts of the world where the infection prevails.
It is especially in some of the Pacific islands, as Samoa and Fiji,
that it is extraordinarily prevalent. Bahr has stated that Fijians
in the proportion of 27% show filarial embryos in their blood. In
25% of these natives clinical manifestations of the disease exist
but the embryos are absent from the peripheral circulation. In
other words more than one-half of the population show absolute
evidence of infection.
LIFE HISTORY
It is a well-known fact that filarial embryos may be present at night
in the peripheral blood of persons not showing a single symptom of
filariasis and again, in those with marked elephantiasis, varicose
groin glands or chyluria there may be an entire and permanent absence
of embryos in the blood. When certain mosquitoes bite persons having
embryos in the blood they take into their stomachs the sheathed
embryos of _F. bancrofti_. Flu states he has succeeded in infecting
the following mosquitoes: _C. fatigans_, _S. scutellaris_, _M.
ludlowi_ and _M. rossii_. The most suitable carriers proved to be _C.
fatigans_ and _S. scutellaris_. Large numbers of larvae perish in
anopheline mosquitoes.
The following developmental cycle has been demonstrated for _Culex
fatigans_ and _Stegomyia pseudoscutellaris_. Bahr has found that
if there are too many embryos taken up by the mosquito the insect
is apt to die, as the result of too heavy an infection; so that
a person harboring many filarial embryos may be less dangerous
than one with a smaller number. Upon reaching the stomach of the
mosquito the sheath of the embryo becomes fixed in the viscid blood
contents and the embryo itself by active motions is able to force
itself from its sheath. This escape usually occurs within two hours
but may take longer. The free embryo then bores its way through the
stomach walls and within twenty-four hours has reached the thoracic
muscles of the mosquito. Within forty-eight hours the embryo begins
to broaden and the anterior and posterior V spots to become more
prominent. About the end of the first week there commences the
formation of an alimentary canal, by which time the developing
larva is about 0.5 mm. long. When the larva is about 0.6 mm. long
an ecdysis apparently takes place. Later on these larvae develop
3 or 4 terminal papillae and make their way to the fleshy labium
of the mosquito’s proboscis. An occasional larva may enter other
structures than the labium but in such case they would be unable to
effect an entrance to their definitive host, man. These larvae in
the proboscis are about 1.5 mm. long and about 20 microns broad.
The mosquitoes have two terminal processes, the labella, separated
from the labium by a thin membranous partition called Dutton’s
membrane. The larvae, having completed their developmental cycle
in the mosquito, which takes about three weeks, and moving down the
labium, break through this membrane when it is put upon a stretch
by the wide separation of the labella at the time of feeding on
the part of the mosquito. It was formerly supposed that the larvae
entered man through the puncture made by the biting parts of the
mosquito, but Bahr has shown by experiments that they effect
an entrance through the intact pores of the skin as does the
ancylostome larva.
These larvae upon entering the human host reach the lymphatic
vessels or glands and in this definitive host (man) the females are
fertilized by the males and give off sheathed larvae from the uterine
opening near the anterior end of the worm.
[Illustration: FIG. 98.—Male (a) and female (b) of _Filaria
bancrofti_. Natural size. (From Greene after Manson.)]