interval, if the drug is discontinued or continued in insufficient
doses. A very careful enquiry is demanded before we can
admit with the author that quinine has no effect on the
occurrence of such relapses.
Subsequently A. Carducci [1905] made a similar analysis
of 50-60 cases at Rome. He infers that relapses at short
intervals occur from the 6th-9th days of apyrexia, mostly
on the 7th day, but that in quartan and tertian a relapse
is often passed over. He recommends i gram of quinine
on the ist, 2nd, 5th, 6th, 8th, 13th, 15th days of apyrexia,
and 1$ gram on the 7th and 14th days in order to check
this weekly return, and so on for months and months. With
this medication he was able to prevent relapses in most of
his cases, but remarks that they recurred if the quinine was
discontinued.
On the whole, after studying this and much other literature,
I think that there is probably no special periodicity in relapses
ā that the periodicity noted by some observers was probably
due rather to their own periodical methods of medication than
to any other cause. If marked periodicity in relapses exists, it
should have been widely observed long before now amongst
the immense number of cases occurring in military practice ā
it would certainly have been observed by the military as well
as by the medical officers. But I can find few notes to this
effect, and certainly remember nothing of the kind in my own
practice. As stated in section 20 (6) I am at present inclined
to think that relapses occur after quite irregular intervals,
determined by secondary causes or insufficient treatment, rather
23] QUININE IN RELAPSES 141
than by any inherent property of the parasites ; but that there
may be some tendency to periodical failure of the germicidal
powers (section 65).
Regarding the reputed failure of quinine to prevent relapses,
I again remain dissatisfied with the evidence. It appears to
me to be merely a question of sufficiency and continuity of
treatment.
On the other hand, there appears to be a large mass of
evidence in favour of Torti's law that quinine should be
administered two or three hours before the commencement
of the paroxysm, if this can be determined.
Many authors ā Laveran, Koch, Manson, Ziemann, Carducci
and others ā have suggested various systems of discontinuous
dosage, such as the administration of large doses once a week,
or twice a week, or every four days, or for two consecutive days
every week, or every seven days after the first day of apyrexia,
and so on. Owing to the temporary retention of the drug in
the blood there is difficulty in understanding the rationale of
such proposals. Moreover, a large dose every few days is
much more distressing to the patient than a smaller dose
every day, and, for this very reason, is apt to be neglected or
postponed by him. There appear to be no evidence that the
Plasmodia become habituated to quinine as trypanosomes do to
atoxyl. Personally, therefore, I prefer the continuous method ;
that is, a dose at least once a day. It seems to have given the
best results in Caccini's cases, and is recommended by Celli.
We should here distinguish carefully between what may be
called medical and hygienic therapeutics. The former is the
therapeutics of the physician at the bedside ; the latter, that
which is to be recommended to the general public ā who are,
in fact, called upon to treat themselves. Refinements in
medication which are possible in the former case are not
possible in the latter one, and therefore the simplest possible
rule is the one which is to be preferred for hygienic therapeutics
(section 36).
142 THE PARASITIC INVASION IN MAN [Sect.
Regarding the duration of treatment required to exterminate
the parasites, we have no complete data. The case of T. Manson,
who was infected in London in 1900 and was treated for three
months, relapsed after nine months. In India the after-treat-
ment of the European troops is continued for six weeks after
discharge from hospital, resulting in a considerable reduction
in the number of admissions. Thus out of ninety primary
cases in two stations there were only seven relapses (" Annual
Report of Sanitary Commissioner, 1907," p. 11). Teaching on
this point differs largely, but I have always given four months
as the Dmthnum period, and doubt whether even this is quite
sufficient. No harm is done if the patient continues some
quinine for six months.
With regard to the different preparations of quinine, much
more strict work by enumerative methods on the effect of the
various salts on the parasites is required. Estimations of the
amounts excreted in the urine and so on give but partial
information on the germicidal action ā which is the point of
importance.
The more soluble salts ā bisulphate, bihydrochloride, hydro-
bromide ā are most easily absorbed, and appear most quickly
in the urine.
The less soluble salts ā sulphate, citrate, tannate, euquinine ā
are absorbed much more slowly, but, finally, in just as much
quantity.
Exact enumerative experiments are therefore required to
decide which of these groups of salts have the most germicidal
action.
Much has been said recently in favour of the tannate,
e.g. by Nardelli [1909] and Deaderick [1909].^ It seems to be
slowly but largely absorbed ; it remains in the blood ; it is
inexpensive, nearly tasteless and very suitable for prophylactic
use by children (section 36).
Methylene Blue ā was suggested for malaria by Guttmann
1 AndCeIli[i9io].
24] SUMMARY 143
and Ehrlich [1891], and has been studied by Thayer [1892],
De Blasi [1902], Wood [1905], Ruge [1906] and others.
Atoxyl has been recently tried by Koch, Grosch [1907]
and various Greek observers. The general conclusion is that
it does reduce the sporids to some extent, but not so well as
quinine. The investigations must be revised and extended.
The methylene blue must be pure, and should be given in
coated pills or capsules up to i gram or more a day ; the
atoxyl may be given by injection up to o'2 grams twice
a week. These and other drugs are not yet of importance
for preventive purposes.
24. Summary. ā The doctrine of the parasite invasion
given above may be summarised as follows : ā
The infecting Anopheline probably injects at a single
feeding from a few to several thousand protospores of one
or more species of Plasmodium.
Many of the injected protospores probably perish ; but the
survivors enter haematids and begin to multiply at an average rate
depending upon their species and, possibly, certain other factors.
When the number of parasites reaches something like
50 per c.mm. of blood the patient begins for the first time to
have definite symptoms of illness.
About the same time some kind of germicidal power which
opposes the invasion begins to come into play, and tends, in
the great majority of cases, to limit the number of parasites
below a fatal number.
At the same time some increasing antitoxic power tends to
reduce their effect upon the host.
The further history of the invasion is probably that of a
constant struggle between the parasites and the germicidal
power, tending, in the great majority of the cases, to the
final victory of the latter.
In untreated or non-immune cases, this struggle generally
144 THE PARASITIC INVASION IN MAN [Sect. 24
produces a long series of relapses, which tend to be precipitated
by many secondary influences acting on the host.
Finally, after this series of rallies and relapses the patient
appears often to reach a stage of partial (or ? complete) immunity.
Possibly, if reinfection does not take place, something like
half the cases tend to recover spontaneously every three months.
The effect of reinfections upon the severity or duration of
the case has not been estimated.
The case may be cut short at any time by death,
spontaneous recovery, or quinine.
There is no reason why we should suppose that the infec-
tion is maintained by encystment or parthenogenesis or other
special arrangements of the parasites, and the existence of
such phenomena has not been proved.
This doctrine can scarcely be verified by the continuous
study of entire cases, and is therefore based rather on the
comparison of different periods in the history of many different
cases, and on reasoning from numerous data.^
The careful student of the literature of the pathology of
malaria will be struck by the immense amount of admirable
work done on the subject. Ideas of number and quantity,
however, are often completely disregarded ā a common fault of
biological work ā with the result that many of the secondary
theories and explanations will require to be examined over again
by more laborious, enumerative and quantitative methods.-
^ I have held it, in the absence of a better doctrine, since 1895, and have always
taught it in my lectures and publications.
" See section 65.
CHAPTER V
MALARIA IN THE COMMUNITY
25. Is the Infection caused otherwise than by Anophelines.ā
Having considered the parasitic invasion of the individual, we
must next examine that of the community.
It was shown in sections i6 and 17 that infection is produced
by the bite of certain mosquitos ; but after proof of this was
obtained, several capable students of malaria expressed a doubt
as to whether this is the only route of infection. We can
scarcely wonder, then, if the general public sometimes have
similar doubts, and the Health Officer must be always prepared
to discuss the matter fully in public. The following questions
are easily answered : ā
( I ). Do mosquitos exist where there is no malaria ? ā They
do ; but this has no application to the subject, as only certain
species carry malaria.
(2). Does malarial fever occur where there are no mosquitos?
ā Very frequently, as on board ship in mid-ocean, on high
mountains, or in Britain in the middle of winter; but such
cases are always relapses.
(3). Do Anophelines exist where there is no endemic malaria ?
ā In many places, as in Britain ; but the presence of infected
persons, as well as of carriers, is required, and, moreover, both
must be in sufficient numbers (section 28).
(4). Does endemic malaria occur where there are no Ano-
phelines? ā No case of this has yet been established. So far
as we know, Anophelines exist in all warm countries, and in
most temperate climates during the summer.
145 K
146 MALARIA IN THE COMMUNITY [Sect.
But the Anophelines are often difficult to find. Thus, I
had been working on the mosquito theory of malaria for two
years before I noticed this group of gnats. Duggan [1897]
said that there were few mosquitos in Freetown, Sierra Leone,
but we found numbers there two years later. In 1901 I
observed none flying about in a new house at Ibadan, Lagos,
West Africa ; but five or six, mostly Anophelines, were captured
two nights in succession within an old mosquito - net with
holes in it, in which a servant slept. If so many had been
able to enter through the holes during the night, how many
(though none were observed) must have been flying about free ?
They abound in Britain, though the general public scarcely
ever notices them. Before the presence of Anophelines in any
locality can be denied, a trained observer must be employed
to search for them. Many workers have made similar notes
on this point.
It does not follow, because the insects are scarce in a locality
at the moment when we visit it, that they do not abound in
it at some other season.
(5). Is it possible to become infected in uninhabited localities ?
ā Some people, such as several sportsmen and travellers I have
met, have stated that they acquired malaria in such places.
One told me that he had frequently been attacked a few
hours after entering a certain big-game district. We ask in
reply {a) what about the incubation period ; {b) whether the
traveller was unaccompanied by servants ; and (c) whether he
had travelled in a balloon ? We must obviously pass through
many inhabited places, where the risks of infection may be
great, before reaching the wilderness ; we must have servants
and carriers with us ; and we may indeed have had the parasites
in our own blood, without knowing it.
(6). If mosquitos become infected froin men and m.en from,
mosquitos, how and when did the process first commence ? ā This
question is always asked by the most intelligent person present ;
and I only wish that we knew the answer. It is concerned
25] INFECTION FROM THE SOIL 147
with the whole subject of the evokition of metaxenous parasites.
Leukart supposes, of course, that they were once free Hving
organisms, which acquired the habit of Hving first in one host
and then, for greater security during the necessary period of
migration, in another; and Grassi, and A. J. Chalmers [1902]
have tried to fit this hypothesis to the case of malaria. But
there are certain grave difficulties, and for the present it is
sufficient to note that, we must be satisfied with the facts as
we find them.
(7). Has it been absolutely proved that malaria does not come
from the soil? ā It is always very difficult to prove a negative
hypothesis of this kind. We never know what surprise Nature
does not keep in store for us ; we are not omniscient, and
wonderful things happen. But the fact that we cannot prove
that malaria does not come from the soil is no proof of the
hypothesis that it does do so. We are not sure that elephants
do not exist in the moon ; but our ignorance here does not
prove that they do exist there. Malaria may just possibly
rise from the soil ; but there is no evidence at all that it does
so. In my experience, those who argue in favour of this
speculation nearly always confound relapses with original
infections. True, we occasionally meet with cases which are
not easy to explain on the mosquito theory, but I have
never met one which could not possibly be explained by it.
On the other hand, there are many strong, very strong,
arguments against the idea that malaria is bred directly in the
soil or in the marsh. In the first place, all experiments to infect
men with air or water brought from malarious localities have
failed (section 17). Secondly, if malaria were due to any
particular kind of soil under certain conditions (as has been
supposed), it should always be present where that soil and
those conditions exist. But we know that actually it comes
and goes. For example, it came to Mauritius in 1866, and
to Reunion in 1867 ; it is still absent from Seychelles and
Rodrigues, though favourable conditions for it exist in those
148 MALARIA IN THE COMMUNITY [Sect.
islands, and it has disappeared from Great Britain. But the
soil and the climate of these areas have not changed. Thirdly,
if the poison is diffused in the air it ought to affect every one
within a considerable area round the generating centre, but
as a rule the disease is limited to the immediate vicinity of
the marsh. Fourthly, the telluric miasm ought to attack
especially those who are engaged in digging, but I have never
obsened that cultivators and gardeners suffer much more than
their neighbours ; while, as a matter of fact, it is generally
the children and even the infants who suffer the most. Lastly,
the idea that the parasites can live in soil, water and air, as
well as in men and mosquitos, is extremely improbable in the
light of our general knowledge of parasites.
The last is probably the clinching argument. Living
organisms do not possess independent properties, but accord
more or less in their structure, capacities, habits and life-history
with other organisms. We are cognisant of thousands of
parasites of men, animals and plants ; and what we know of
the parasites of malaria shows that they are not markedly
exceptional. In fact they belong to a class of parasites which
infect two hosts, one of which feeds on the other ā as, for
instance, {>arasites of the deer and the tiger, the mouse and
the cat, the ox and man, the ox and the cattle tick, and now
man and mosquitos. The general law is, therefore, satisfied
by the known life-histor)- of malaria. We have no reason to
expect another life-history for the malaria parasites in soil,
water or air, any more than for the other parasites. Then
again, every animal possesses only the limited p>owers which
have been given to it by the evolution of ages, and for which
it has acquired definite organs and habits of life. The mole
burrows, the fish swims, the bird flies, the parasite occupies
the higher animal or plant But if this telluric h\pothesis is
sound, what remarkable animals must these parasites of malaria
be ! They already possess a structure wonderfully adapted
for their life in men and also in mosquitos ; but we must now
25l OTHER CARRIERS 149
expect that they are also able to burrow like the mole, swim
like the fish, and fly like the bird ! To do all these things they
must have the suitable organs ; and not only this, but they or
their spores must be protected against heat and cold and hosts
of enemies in soil, water and air. If all this were true we
should have to put the parasites of malaria in a special class
by themselves, apart from the rest of creation.
These reasons have now led pathologists and parasitologists
(who can perhaps appreciate their weight better than others)
to abandon the telluric hypothesis as a likely one. There is
no evidence in favour of it, and there are very strong arguments
against it. The true theorem is obvious. The connection
between malaria and the marsh, so long known to suffering
humanity, is now fully explained by the fact that the Anophelines
breed in the marsh. There is no necessity to believe that the
germs also breed in the marsh. Malaria comes from the marsh,
not because the germs of the disease come from it, but because
the carriers of the germs do so. It is the same thing in the
end. The ancient theory was quite right. Malaria is caused by
a marsh miasm. The Anophelines themselves, the mosquitos,
are the marsh miasm.
(8). Do other insects besides Anophelines carry malaria ? ā
First we should note that not all, but only certain species of
Anophelines carry it, and that according to some, only certain
varieties of some of these species are effective. As a fairly
general rule, animal parasites are very particular in their
choice of hosts. Thus no one has succeeded in infecting
animals with human malaria, and the probability is that it will
not exist in many kinds of mosquitos. Between 1895 and 1899
I failed entirely in infecting several species of Culex and
Stegomyia, though I made experiments on hundreds of the
insects ; and these results were confirmed by the Italian
observers, by Stephens and Christophers, and by many others.
But, nevertheless, such negative results are never absolutely
conclusive unless enormous numbers of experiments are made,
ISO MALARIA IN THE COMMUNITY [Sect.
because it is always possible that some condition such as of
temperature or humidity may have been overlooked, or that
the proper species or variety may not have been used. But
there is a strong argument against mosquitos in general being
concerned, namely, that from the oldest times malaria has
been known to be connected with marshes, while many
mosquitos, such as most Culex and Stegojnyia, do not breed
in marshes as a rule, but in petty collections of water round
houses. If these carry malaria, then malaria should abound
everywhere, especially in towns, and not so exclusively near
marshes. A good contrast is found in the case of yellow fever,
which does abound in towns and not particularly near marshes
ā for the simple reason that it is carried by Stegomyia.
On the whole, then, though we cannot say definitely that
malaria is not carried by other hosts than Anophelines, yet
there are strong reasons for this opinion. At all events we are
fairly certain that most insects which carry it must be marsh-
born, like the Anophelines ; so that the principal preventive
measure of drainage is not seriously affected by the question.
(9). Do the human parasites live also in animals? ā In 1898
in Calcutta, my servant, Mahomed Bux, became, suddenly
infected with malaria, which he thought he had acquired while
collecting mosquitos fed on infected birds. At present, how-
ever, no one thinks that the parasites of men and of animals
are the same. The attempts of Di Mattel and others to infect
birds from men were all negative.
( I o). Do the parasites enter the eggs and larvae of mosquitos ? ā
In 1898 also, I thought that the protospores of P. danilevskyi
might enter the eggs of the carrying mosquitos, but all my
attempts to find them there were failures. More recently
Schaudinn [1904] has sought to revive this hypothesis ; but he
gave no proof of it. Such a thing happens, however, with
Piroplasma in ticks, and has been suggested as possible in the
case of yellow-fever. If it happens in malaria, the parasites
would be passed on, not only from mosquito to man, but also
26] DEFINITIONS 151
from mosquito to mosquito. I have had no opportunities for
examining the subject further, but may add that my studies on
the point in 1898 were very careful. We should not accept the
suggestion, even tentatively, without much better evidence.
26. Some Definitions. ā We are therefore almost sure that
infection with the parasites of malaria occurs in nature only
through the bites of mosquitos ā probably only of certain
species of Anophelines. But this statement is not nearly
sufficient for all the purposes of prevention, and we must
discuss the subject in much greater detail. Why does the
disease vary in amount from place to place, or even in the
same place from season to season, or year to year ? Why does
it disappear from some countries and appear in others? The
whole subject of the prevention of malaria is based upon a
rational study of these questions, and the reader who is called
upon to undertake such work must exert himself to consider
them thoroughly. We must first have clear ideas upon the
following points : ā
(i). The cases of malarial fever which occur within a
given locality belong, of course, to two classes, the
indigenous cases and the imported cases. The first
are those who were infected within the locality ;
the latter, those who were infected outside it, but
who, after immigration, remain infected within it.
The latter class may be very numerous in military
stations, hill stations, and sanatoria. But they also
abound in many villages of which the inhabitants
are given to working elsewhere during the malarious
months ; and among bands of immigrant workmen.
On the other hand, in small towns and villages with
fixed populations most of the cases are apt to be
indigenous ones. It is often difficult to determine
the proportion of each class because many of the
imported cases may be reinfected within the area
152 MALARIA IN THE COMMUNITY [Sect.
of observation, while many of the indigenous cases
may have emigrated since infection.
(2). By the malaria rate of a locaHty I mean the percentage
of persons who contain plasmodia at some given
moment. We may divide this into the indigenous
malaria rate and the imported malaria rate. The
former may also be called the malarial endemicity of
the place.
(3). By the malaria index, or endemic index, of a locaHty
I mean the percentage of persons in whom any
evidence of malarial infection was found at some
given moment. It will be clear from Chapter IV
that such evidence cannot generally be found in
all the cases of malaria in a locality ā many may
contain plasmodia without showing them or any
objective symptoms of them. Conversely, many
people may show evidence of past infection, such
as enlarged spleen, without containing plasmodia
at the moment. We may divide the endemic (or
malaria) index into the adult, the juvenile and the
infantile endemic index}
(4). By the daily, monthly or annual inoculation rate of
a locality I mean the percentage of persons who
were inoculated or reinoculated by mosquitos during
the day, month or year referred to.
(5). When we talk of the amount of malarial fever in a
locality we generally refer to the total malaria rate
in it. When we talk of the amount of malaria in
it we generally mean its indigenous malaria rate.
When we say that a place or a season is very
malarious, we mean that the inoculation rate is very
high for that place or season.
1 The term " endemic index " was first used by Stephens and Christophers to denote
the percentage of children showing the parasites in the blood, but the above