Chapter X: Part II (5)

At the end of 1899, this treatment, only just out of the hands of science, was suddenly demanded for the protection of a huge army at war in a country saturated with typhoid. Still, the South African results, and other results during 1899 to 1901, show a good balance of lives saved. The following paragraphs give all results published from the beginning of 1900 to May 1902. They are put in order of publication. Doubtless a few other reports have been overlooked in compilation; but the list includes all that were easily accessible.

1. _Manchester, England._ The _British Medical Journal_, 28th April 1900, contains a note by Dr. Marsden, Medical Superintendent of the Monsall Fever Hospital, Manchester, on the inoculation of 14 out of 22 nurses engaged in nursing typhoid patients. Of the remaining 8, 4 had already had typhoid. The inoculations were made in October 1899. The following table shows the subsequent freedom from typhoid of the nursing staff:--

+-------------------------------+-----------------+--------------+
| Year. | Number of | Cases among |
| |Typhoid Patients.|Nursing Staff.|
+-------------------------------+-----------------+--------------+
| 1895 | 229 | 3 |
| 1896 | 238 | 3 |
| 1897 | 302 | 4 |
| 1898 | 426 | 8 |
| To end of September 1899 | 163 | 5 |
|From October 1899 to March 1900| 146 | 0 |
+-------------------------------+-----------------+--------------+

2. _Ladysmith, South Africa._ The _Lancet_, 14th July 1900, contains a short note by Professor Wright, on the distribution of typhoid among the officers and men of the military garrison, during the siege of Ladysmith. The figures are as follows:--

+-------------+-------+------+----------+-------+----------+----------+
| |Number.|No. of|Proportion|No. of |Proportion| Case- |
| | |Cases.|of Cases. |Deaths.|of Deaths.|mortality.|
+-------------+-------+------+----------+-------+----------+----------+
|Not | | | | | | |
| inoculated |10,529 | 1489 |1 in 7.07 | 329 | 1 in 32 |1 in 4.52 |
|Inoculated | 1,705 | 35 |1 in 48.7 | 8 | 1 in 213 |1 in 4.4 |
+-------------+-------+------+----------+-------+----------+----------+

The wide difference between the two groups, as regards the incidence of the disease, is well marked; but the case-mortality is practically the same in each group. (The statistics of the General Hospital, Ladysmith, also tell in favour of the preventive treatment: see Surgeon-Major Westcott's letter, _British Medical Journal_, 20th July 1901, in answer to Dr. Melville's letter, _British Medical Journal_, 20th April 1901.)

3. _The Portland Hospital: Modder River and Bloemfontein_. The _British Medical Journal_, 10th November 1900, contains an account by Dr. Tooth of the cases of typhoid in this hospital. Concerning the preventive treatment, he says: "The experience of my colleague Dr. Calverley and myself may be of interest, though we fear that the numbers are too few for safe generalisation.

"_Personnel of the Portland Hospital._ We take first the relation of disease and inoculation among the _personnel_ of the hospital. Twenty-four non-commissioned officers, orderlies, and servants of the Portland Hospital, and 4 of the medical staff, were inoculated on the voyage out. All these showed the local symptoms at the time; that is, pain, stiffness, and local erythema; 17 also presented well-marked constitutional symptoms--general feeling of illness, fever, and headache. Of the orderlies, 9 had enteric fever subsequently. Two had refused inoculation, and both of these had the disease very severely; in fact one died. Of the inoculated cases, 5 had the disease lightly, and 2 fairly severely. One of the sisters had the disease rather severely, and she had not been inoculated.

"_Officers and men admitted to the Portland Hospital._ We had under treatment at the Portland Hospital 231 cases of enteric fever, most of which came under our care at Bloemfontein. We have not included in these figures a number of patients who came in convalescent for a short time only, and on their way to the base, and who would therefore appear in the admission and discharge book of the hospital. If we did so, of course our percentages would be lower. Of these 231 patients, 53 had been inoculated at home or on the voyage out, and of them 3 died, making a percentage of deaths among the inoculated of 5.6 per cent.; 178 had not been inoculated, of whom 25 died; that is, a mortality among the non-inoculated of 14 per cent. The general mortality in enteric fever with us was 28 deaths out of 231 cases; that is, 12.1 per cent., which seems to compare favourably with the experience of the London hospitals.

"It is interesting to record our experience among the officers taken separately. Thirty-three officers were admitted with enteric fever; 21 had been inoculated; that is, 63.6 per cent.; a much larger percentage than among the men. Only one of these officers died, and he had not been inoculated.

"These figures are small, but such as they are they are significant, and they dispose us to look with favour upon inoculation. So also does our clinical experience with our patients, for among the inoculated the disease seemed to run a milder course."

4. _No. 9 General Hospital, Bloemfontein._ The _Medical Chronicle_ for January 1901 contains an account, by Dr. J. W. Smith, of the work of this hospital. He says: "The general impression amongst the medical officers in our hospital was that a single inoculation probably did not confer an immunity lasting very long--the lapse of time differing in individuals--and also that there was a tendency in the cases of enteric in inoculated patients to abort at the end of ten or fourteen days. I should say, however, that a very considerable number of our detachment who had been inoculated suffered from enteric, of whom 4 at least died. Of the medical staff, the only member of the junior staff who had not been inoculated died of enteric."

5. _Scottish National Red Cross Hospital, Kroonstadt._ The _British Medical Journal_, 12th January 1901, contains an account of the work of this hospital by Surgeon-Colonel Cayley, Officer in Charge. He says: "The first section of the hospital, consisting of 61 persons--officers, nursing sisters, and establishment--left Southampton on 21st April 1900. During the voyage out, all except 4 were inoculated twice, at an interval of about ten days; 2 were inoculated once; and 2 (who had had typhoid) were not inoculated. Immediately we reached the Cape, the hospital was sent up to Kroonstadt in the Orange River Colony, and remained there as a stationary hospital till the middle of October. During this period there were always many cases of enteric under treatment in hospital. Further, some of the medical officers and student orderlies had charge of the Kroonstadt Hotel temporary hospital, which was crowded up with enteric cases; and the nursing sisters, for three weeks, did duty in the military hospitals at Bloemfontein in May and June, when enteric fever was at its worst. There was not a single case of enteric among the _personnel_ of this first section of the hospital.

"The second section of the hospital--medical officers, nurses, and establishment, 82 in all--left Southampton in May 1900. On board ship nearly all of them were inoculated, but many of them only once. The material for inoculation had been on board for some time, and was not so fresh as in the first instance. Of this second section, 1 nurse had enteric at Kroonstadt. She was the only one, out of a total of 36 nurses, who suffered from enteric; and she was the only nurse who was not inoculated, excepting the 2 who were protected by a previous attack of enteric. A third section of the hospital, consisting of 4 medical officers and 16 nurses, went out in July; they were all inoculated, and none of them had enteric.

"Of the second section, 5 orderlies had enteric fever at Kroonstadt, of whom 2 died. Of these 5, there were 2 inoculated (once) and 3 non-inoculated. Of the 2 who died, 1 had been once inoculated, the other had not been inoculated."

6. _Meerut, India._ The _British Medical Journal_, 9th February 1901, gives a short note by Professor Wright on inoculations in the 15th Hussars. He says: "Through the kindness of Lieutenant-General Sir George Luck, commanding the Bengal Army, I am permitted to publish the following officially compiled statistics, dealing with the effects of anti-typhoid inoculations in the case of the 15th Hussars:--

_From 22nd October 1899 to 22nd October 1900._

+---------------+---------+-----------+------+-------+
| | | | | |
| |Strength.|Inoculated.|Cases.|Deaths.|
+---------------+---------+-----------+------+-------+
|Officers | 22 | 19 | 0 | 0 |
|N.C.O. and Men | 481 | 317 | 2 | 1 |
|Women | 36 | 24 | 0 | 0 |
+---------------+---------+-----------+------+-------+

+---------------+-----------+------+-------+
| |Not | | |
| |Inoculated.|Cases.|Deaths.|
+---------------+-----------+------+-------+
|Officers | 3 | 0 | 0 |
|N.C.O. and Men | 164 | 11 | 6 |
|Women | 12 | 0 | 0 |
+---------------+-----------+------+-------+

It would thus appear that the incidence of enteric in the inoculated was represented by 0.55 per cent., and the mortality by 0.27 per cent.; while the incidence in the uninoculated was 6.14 per cent., and the death-rate 3.35 per cent."

If the inoculated had suffered equally with the uninoculated, they would have had 22 cases with 11 deaths, instead of 2 cases with 1 death.

7. _The Edinburgh Hospital, South Africa._ The _Scottish Medical and Surgical Journal_, March 1901, contains an account of the work of the Edinburgh Hospital, by Dr. Francis Boyd. Of the staff, 58 were inoculated (27 once, and 31 twice). Among these 58, there were 9 cases of typhoid fever, with I death, in a patient who had old mitral disease. "Our experience has been that, while inoculation appears to modify the disease, completely modified attacks are met with in the uninoculated. Again, very severe attacks, with complications and relapse, occur in those who have been inoculated. One cannot from this conclude that inoculation has been valueless, for had not the patient been inoculated, the attack might have been still more severe."

8. _Egypt and Cyprus._ The _British Medical Journal_, 4th May 1901, gives a short note by Professor Wright on inoculations during 1901 in Egypt and Cyprus. He says: "I am indebted to the kindness of Colonel W. J. Fawcett, R.A.M.C., Principal Medical Officer in Egypt, for the following statistics dealing with the incidence of enteric fever, and the mortality from the disease, for the year 1900, in the inoculated and uninoculated among the British troops in Egypt and Cyprus:--

+------------------------------------------------------------------+
| |Average Annual|Cases.|Deaths.|Percentage|Percentage |
| | Strength. | | | of Cases.| of Deaths.|
|-------------+--------------+------+-------+----------+-----------|
|Uninoculated | 2669 | 68 | 10 | 2.50 | 0.40 |
|Inoculated | 720 | 1 | 1 | 0.14 | 0.14 |
+------------------------------------------------------------------+

These figures testify to a nineteen-fold reduction in the number of attacks of enteric fever, and to a threefold reduction in the number of deaths from that disease, among the inoculated.... The only case which occurred among the inoculated was that of a patient admitted to hospital on the thirty-third day after inoculation. It would seem that the disease was in this case contracted before anything in the nature of protection had been established by the inoculation."

9. _Imperial Yeomanry Hospital, Pretoria._ Dr. Rolleston, Consulting Physician to this hospital, writes in the _British Medical Journal_, 5th October 1901: "Among the _personnel_ of the hospital (17 medical officers, 50 nursing sisters, 83 orderlies, etc.), total, 150, there were 22 cases of enteric fever, or an incidence of 14.6 per cent. Of the 150, 35 were inoculated, and of these, 6, or 17 per cent., suffered from enteric; while, of 115 non-inoculated members of the _personnel_, 16, or 13.9 per cent., suffered from enteric fever; the percentage is therefore higher among the inoculated. There were 2 deaths, both in non-inoculated patients. In 100 cases of enteric fever among non-commissioned officers and men, taken mainly from convalescent patients, only 8 had been previously inoculated; there were 3 fatal cases, all among non-inoculated patients. Among 42 officers who had enteric, no fewer than 19 had been previously inoculated; 6 of these 19 cases were severe in character, but none were fatal; of the 23 non-inoculated cases, 7 were severe, and of these 7, 3 ended fatally. The interval between inoculation and the subsequent incidence of enteric fever varied between one and twenty-one months, but in only four instances was the interval less than six months. The average interval between inoculation and the onset of enteric fever in these 19 cases was thirty-eight weeks.

"As far as these scanty figures go, they point to the conclusion (1) that anti-typhoid inoculation does not absolutely protect against a future attack of typhoid fever; (2) that when enteric occurs in an inoculated person, there is, as a rule, an interval of about six months; (3) that inoculation protects against a fatal termination to the disease."

10. _Richmond Asylum, Dublin._ The _British Medical_ _Journal_, 26th October 1901, contains a note by Professor Wright on an outbreak of typhoid in this asylum during August to December 1900. Inoculations were begun on 6th September, by Dr. Cullinan, and by 30th November 511 persons were inoculated. After careful criticism of all doubtful cases, Professor Wright gives the following figures:--

_Comparative Incidence of Typhoid Fever in Inoculated and
Non-Inoculated, calculated upon the average strength of the
representative groups during the period intervening between the
commencement of the inoculations and the termination of the
epidemic._

+--------------+---------+-------+-------+----------+----------+
| |Average |Cases. |Deaths.|Percentage|Percentage|
| |Strength.| | |of Cases. |of Deaths.|
+--------------+---------+-------+-------+----------+----------+
|Uninoculated | 298 |30(-1?)| 4 | 10.1 | 1.3 |
|Inoculated | 339 | 5(+1?)| 1 | 1.3 | 0.3 |
+--------------+---------+-------+-------+----------+----------+

"It may be noted," he says, "that the result is in conformity with that of all the statistical returns of anti-typhoid inoculation which have reached me."

11. _Deelfontein._ The _Lancet_, 18th January 1902, contains a paper by Dr. Washbourn and Dr. Andrew Elliot, on 262 cases of typhoid fever in the Imperial Yeomanry Hospital at Deelfontein during the year March 1900 to March 1901. (See Dr. Washbourn's earlier letter, _Brit. Med. Jour._, 16th June 1900.) They say: "In 211 of our cases, it was definitely recorded whether the patient had been inoculated or not: 186 of these cases had not been inoculated, with 20 deaths, or a mortality of 10.7 per cent.; 25 had been inoculated, with 4 deaths, or a mortality of 16 per cent. The mortality was thus higher among the inoculated than among the non-inoculated." Of the _personnel_ of the hospital, there were 59 inoculated, with 4 cases, and 25 not inoculated, with 4 cases.

12. _Winburg._ The _Lancet_, 5th April 1902, contains a short note by Professor Wright, on the 5th Battalion, Manchester Regiment. He says: "In view of the dearth of statistics bearing on the incidence of typhoid fever in South Africa in inoculated and uninoculated persons respectively, the following, for which I am indebted to Lieutenant J. W. West, R.A.M.C., Winburg, Orange River Colony, may not be entirely without interest. The statistics here in question give the results obtained in the case of the 5th Battalion, Manchester Regiment, for the six months which have elapsed since their landing in South Africa. The figures, which relate to a total strength of 747 men and officers under observation, are as follows:--

+--------------+---------+-------+-------+----------+----------+
| | Number. |Cases. |Deaths.|Percentage|Percentage|
| | | | |of Cases. |of Deaths.|
+--------------+---------+-------+-------+----------+----------+
|Uninoculated | 547 | 23 | 7 | 4.2 | 1 in 3.3 |
|Inoculated | 200 | 3 | 0 | 1.5 | 0 |
+--------------+---------+-------+-------+----------+----------+

"The three attacks in the inoculated are reported to have been of exceptionally mild type, contrasting in a striking manner with the severe attacks which occurred in the uninoculated. At the time of sending in the report, some of the uninoculated patients were 'not yet out of danger.'"

* * * * *

Certainly, these instances show a good balance of lives saved, not only under the adverse conditions of the war, but also in Egypt, India, and the United Kingdom. But the bacteriological work on typhoid fever has been directed also to the working out of a very different problem: and that is the method of diagnosis which is called "Widal's reaction." The practical uses of this reaction are of the utmost importance. It is the outcome of work in different parts of the world--by Wright and Semple and Durham in England, Chantemesse and Widal in France, Pfeiffer and Kolle and Grüber in Germany, and many more. The first systematic study of it was made by Durham and Pfeiffer; and Widal's name is especially associated with the application of their work to the uses of practice. Admirable accounts of the whole subject are given by Dr. Cabot in his book, _The Serum-Diagnosis of Disease_ (Longmans, 1899), and by Mr. Foulerton in the _Middlesex Hospital Journal_, October 1899 and July 1901.

Widal's reaction is surely one of the fairy tales of science. The bacteriologist works not with anything so gross as a drop of blood, but with a drop of blood fifty or more times diluted; one drop of this dilution is enough for his purpose. Take, for instance, an obscure case suspected to be typhoid fever: a drop of blood taken from the finger is diluted fifty or more times, that the perfect delicacy of the test may be ensured; a drop of this dilution is mixed with a drop of nutrient fluid containing living typhoid bacilli, and a drop of this mixture of blood and bacilli is watched under the microscope:--

"The motility of the bacilli is instantaneously or very quickly
arrested, and in a few minutes the bacilli begin to aggregate
together into clumps, and by the end of the half-hour there will
be very few isolated bacilli visible. In less marked cases, the
motility of the bacilli does not cease for some minutes; while
in the least marked ones the motility of the bacilli may never
be completely arrested, but they are always more or less
sluggish, while clumping ought to be quite distinct by the end
of the half-hour."

The result of this clumping is also plainly visible to the naked eye, by the subsidence of the agglutinated bacteria to the bottom of the containing vessel: and thus an easy practical mode of diagnosis is afforded by it.

As with typhoid, so with Malta fever, cholera, and some other infective diseases. And the unimaginable fineness of this reaction goes far beyond the time of the disease. Months, even years, after recovery from typhoid, a fiftieth part of a drop of the blood will still give Widal's reaction: and it has been obtained in an infant whose mother had typhoid before it was born. A drop of dried blood, from a case suspected to be typhoid, may be sent a hundred miles by post to be tested; and typhoid, like diphtheria, may now be submitted to the judgment of an expert far away, and the answer telegraphed back. It would be difficult to exaggerate the practical importance of this reaction for the early diagnosis of cases of typhoid fever, especially those cases that appear, at the onset, not severe.

MALTA FEVER

The specific organism of Malta fever (Mediterranean fever), the _bacillus Melitensis_, was discovered in 1887 by Surgeon-Major David Bruce, of the Army Medical Staff. Its nature and action were proved by the inoculation of monkeys. The use of Widal's reaction is of great value in this disease:--

"The diagnosis of Malta fever from typhoid is, of course, a
highly important practical matter. It is exceedingly difficult
in the early stages." (Manson, _loc. cit._)

As with typhoid, so with Malta fever, Netley led the way to the discovery of an immunising serum. In the course of the work, one of the discoverers was by accident infected with the disease:--

"He was indisposed when he went to Maidstone to undertake
anti-typhoid vaccination, and after fighting against his illness
for some days, he was obliged to return to Netley on 9th
October. Examination of blood-serum (Widal's reaction) showed
that he was suffering from Malta fever. It appears that he had
scratched his hand with a hypodermic needle on 17th September,
when immunising a horse for the preparation of serum-protective
against Malta fever; and his blood, when examined, had a typical
reaction on the micrococcus of Malta fever in 1000-fold
dilution. The horse, which has been immunised for Malta fever
for the last eight months, was immediately bled, and we are
informed that the patient has now had two injections, each of 30
cub. cm. of the serum. He is doing well, and it is hoped that
the attack has been cut short." (_British Medical Journal_, 16th
October 1897.)

About fifty cases had up to September 1899 been treated at Netley "with marked benefit: whereas they found that all drug-treatment failed, the antitoxin treatment had been generally successful."[36] A good instance of the value of the serum-treatment of Malta fever is published in the _Lancet_, 15th April 1899. For a later account of this treatment and of its efficacy, see the _Philadelphia Medical Journal_, 24th November 1900.

[36] For the whole subject, see _Lancet_, 9th September 1899,
paper by Surgeon-Major Birt and Surgeon-Captain Lamb. Two other
cases of accidental inoculation occurred at Netley.

Another point is noted by Sir Patrick Manson, in his recent Lane Lectures (Constable, 1905). "For some time back," he says, "a commission of experts, working under the direction of the Royal Society, has been studying this disease in Malta. The commission has accumulated much detailed information; but the most important observation it has published is the fact that a large percentage of the goats in Malta are infected with _Micrococcus melitensis_, and that the milk of the infected goats contains the bacterium. May not this account for the great prevalence of Mediterranean fever there and in other places having perhaps a similar milk-supply?"

X

THE MOSQUITO: MALARIA, YELLOW FEVER, FILARIASIS

Within the last few years, it has been proved that the mosquito is an intermediate host, between man and man, of malaria, yellow fever, and filariasis (elephantiasis).[37] Just as the grosser parasites, the tapeworms, must alternate between man and certain animals, and cannot otherwise go through their own life-changes and reproduce their kind, so the micro-parasites that are the cause of malaria alternate between man and the mosquito, having the mosquito as an intermediate host. These organisms, once they get into the mosquito, pick out certain structures, and there carry out a definite cyclical phase of their lives, whereby their progeny make their way into the stylets of the mosquito, and so get back to man, who is their "definite host." Thus, malaria is not, strictly speaking, a disease of man; it is one phase in man of micro-organisms that have another phase in mosquitoes. So also with filariasis; the filariæ in man, their ova, and their embryo-worms, are one phase of filariasis; and the embryo-worms in certain structures of the mosquito are another phase. The _plasmodium malariæ_ and the _filaria_ are instances of a law of animal life that holds good also of plant life:--

"All plants and animals possess parasites, and thousands of
different species of parasites have been closely studied by
science; we therefore know much about their general ways of
life. As a rule, a particular species of parasite can live only
in the particular species of animal in which, by the evolution
of ages, it has acquired the power of living. It is therefore
not enough for the parasites of an individual animal--say a
man--to be able to multiply within that individual, but they
must also make arrangements, so to speak, for their progeny to
enter into and infect other individuals of the same species.
They cannot live for ever in one individual; they must spread in
some way or other to other individuals.

"The shifts made by parasites to meet this requirement of their
nature are many and various, and constitute one of the wonders
of nature. Some scatter their spores and eggs broadcast in the
soil, water, or air, as it were in the hope that some of them
will alight by accident on a plant or animal suitable for their
future growth. Many parasites employ, in various ways, a second
species of animal as a go-between. Thus, some tapeworms, and the
worms which cause trichinosis, spend a part of their lives in
the flesh of swine, and transfer themselves to human beings when
the latter eat this flesh. To complete the cycle, the parasites
return to swine from human offal; so that they propagate
alternately from men to swine, and from swine to men. The
blood-parasites which cause the deadly tsetse-fly disease among
cattle in South Africa are transferred from one ox to another on
the proboscis of the ox-biting or tsetse-fly. The progeny of the
flukes of sheep enter a kind of snail, which spreads the
parasites upon grass. The progeny of the guinea-worm of man
enter a water-flea. The progeny of the parasites which cause
Texas cattle-fever, and which are very like the malarial
parasites, live in cattle-ticks, and are transferred by the
young of these ticks into healthy cattle." (Ross, _Malarial
Fever_, 1902.)

[37] For Dr. Graham's experiments at Beyrout, which seem to prove
that the mosquito can also convey dengue or dandy-fever, see the
_New York Medical Record_, 8th February 1902.

1. MALARIA

The _plasmodium malariæ_ was discovered by Laveran in 1880, in the blood of malarial patients. For many years his work stopped there, because it was impossible to find the _plasmodium_ in animals: "the difficulties surrounding the subject were so great that this discovery seemed to be almost hopeless." In 1894, Sir Patrick Manson--who had proved mosquitoes to be the intermediate host in the case of the parasitic nematode _filaria_--suggested, as a working theory of malaria, that the plasmodium was carried by mosquitoes. This belief, not itself new, he made current coin. He observed that there is a flagellate form of the plasmodium, which only comes into existence after the blood has left the body: and he suggested that the flagella might develop in the mosquito as an intermediate host, a halfway-house between man and man. Then, in 1895, Ross set to work in India, keeping and feeding vast numbers of mosquitoes on malarial blood; and for two years without any conclusive result. About this time came MacCallum's observations, at the Johns Hopkins University, on a parasitic organism, _halteridium_, closely allied to the plasmodium malariæ; he showed that the flagella of the halteridium are organs of impregnation, having observed that the non-flagellated form, which he regarded as the female, after receiving one of the flagella, changed shape, and became motile. In August 1897, Ross found bodies, containing pigment like that of the malarial parasite, in the outer coat of the stomach of one kind of mosquito, the grey or dapple-winged mosquito, _Anopheles maculipennis_, that had been fed on malarial blood. In February 1898, he was put on special duty under the Sanitary Commissioner with the Government of India, to study malaria, and started work again in Calcutta:--

"Arriving there at a non-fever season, he took up the study of
what may be called 'bird malaria.' In birds, two parasites have
become well known--(1) the halteridium, (2) the proteosoma of
Labbé. Both have flagellated forms, and both are closely allied
to the plasmodium malariæ. Using grey mosquitoes and
proteosoma-infected birds, Ross showed by a large number of
observations that it was only from blood containing the
proteosoma that pigmented cells in the grey mosquito could be
got; therefore that this cell is derived from the proteosoma,
and is an evolutionary stage of that parasite. Next, Ross
proceeded to find out its exact location, and found that it lay
among the muscular fibres of the wall of the mosquito's stomach.
It grows large (40-70 micro-millimetres) and protrudes from the
external surface of the stomach, which under the microscope
appears as if covered with minute warts." (Manson, at Edinburgh
meeting of British Medical Association, 1898.)

These pigmented spherical cells give issue to innumerable swarms of spindle-shaped bodies, "germinal rods"; and in infected mosquitoes Ross found these rods, in the glands that communicate with the proboscis. Thus the evidence was complete, that the plasmodium malariæ, like many other parasites, has a special intermediate host for its intermediate stage of development; and that this host is the dapple-winged mosquito. It is impossible to over-estimate the infinite delicacy and difficulty of Ross's work; for instance, in his "Abstract of Recent Experiments with Grey Mosquitoes," he says that "out of 245 grey mosquitoes fed on birds with proteosoma, 178, or 72 per cent., contained pigmented cells; out of 249 fed on blood containing halteridium, immature proteosoma, &c., not one contained a single pigmented cell." Another time (April 1898) he counted these pigment-cells under the microscope:--

"Ten mosquitoes fed on the sparrow with numerous proteosoma
contained 1009 pigmented cells, or an average of 101 each. Ten
mosquitoes fed on the sparrow with moderate proteosoma contained
292 pigmented cells, or an average of 29 each. The mosquitoes
fed on the sparrow with no proteosoma contained no pigmented
cells."

Finally, he completed the circle of development by infecting healthy sparrows by causing mosquitoes to bite them.

In 1899, there went out a German Commission to German East Africa, a Royal Society's Commission to British Central Africa, and an expedition from the Liverpool School of Tropical Medicine; in 1900, another German Commission, this time to the East Indies, and another expedition from the Liverpool School; by July 1901, the Liverpool School was organising its seventh expedition. Italy, of course, has given infinite study to the disease:--

"It has been decided that, in addition to the stations of
observation and experiment in the provinces of Rome, Milan,
Cremona, Mantua, Gercara, Foggia, Lecce, others shall be
established in the provinces of Udine, Verona, Vicenza, Padua,
Ravenna, Pisa, Basilicata, and Syracuse. Besides epidemiological
researches, applications on a large scale will be made of
preventive measures for the protection of the agricultural
population against the scourge. Another extensive experiment on
the prophylaxis of malaria will be made on the Emilian
littoral. Moreover, in all the malarious regions of the Italian
peninsula the provincial and communal administrations and many
private persons will co-operate in the application of preventive
measures. From all this it may be gathered that during the
summer and autumn the war against malaria will be carried on in
Italy with great vigour and thoroughness." (_British Medical
Journal_, 6th July 1901.)

In India, the work started in 1900 by the Royal Society Commissioners, and by the Nagpur Conference, has been widely extended; especially by such researches as those of Major Buchanan, I.M.S., Superintendent of the Central Jail, Nagpur. The following paragraph, from the report of the Sanitary Commissioner with the Government of India, refers to Major Buchanan's published work, _Malarial Fevers and Malarial Parasites in India_:--

"A remarkable note is struck at the outset, in the
acknowledgment made, by the author, of the capable assistance
rendered in these researches by several of his Burmese
prisoners, whom he trained to the use of the microscope, and who
soon became expert in detecting and distinguishing the various
kinds of parasites.... Besides a systematic clinical account of
the different forms of fever and the associated parasites, which
is the first attempt of the kind in India, there are a summary
of the facts showing the relation of the seasonal prevalence of
_Anopheles_ to the incidence of attacks; experiments exhibiting
the protective effects of mosquito-curtains;
inoculation-experiments; researches on the blood-parasites of
birds; and many other points.... Nor can we pause to notice the
many attempts now being made by health officers and others to
pursue the methods of prophylaxis indicated; these efforts are
necessarily in the tentative stage, but, so far, and especially
where carried out in connection with small communities and
institutions, they are giving promise of gratifying success."

The famous experiment made by Dr. Sambon and Dr. Low in 1900, must be recalled here:--

"Dr. Luigi Sambon and Dr. G. C. Low, both connected with the
London School of Tropical Medicine, volunteered to live from
June till October, that is to say, through what may be called
the height of the malaria season, in a part of the Campagna near
Ostia, which is so infested by the disease that no one who
spends a night there under ordinary conditions escapes the
effect of the poison. Dr. Sambon, Dr. Low, Signor Terzi, and
their servants, have now exposed themselves to the pestilential
influence of this valley of the shadow of death for over two
months. They live in a mosquito-proof hut; they take no
quinine or other drug which might be regarded as prophylactic.
Not one of the experimenting party has the least sign of
infection.[38]...

"What for practical purposes may be regarded as an experiment of
the same kind is being conducted in West Africa. Dr. Elliot, a
member of the Liverpool expedition sent to Nigeria some time ago
to investigate the subject of malarial fever, has recently
returned to this country. He reports that the members of the
expedition have been perfectly well, although they have spent
four months in some of the most malarious spots. They lived
practically amongst marshes and other places hitherto supposed
to be the most deadly. They have not kept the fever off by the
use of quinine, and they attribute their immunity to the careful
use of mosquito-nets at night." (_British Medical Journal_, 22nd
September 1900.)

[38] Sir Patrick Manson, in the _British Medical Journal_, 29th
September 1900, gives the following account of this
experiment:--"A wooden hut, constructed in England, was shipped to
Italy and erected in the Roman Campagna, at a spot ascertained by
Dr. L. Sambon, after careful inquiry, to be intensely malarial,
where the permanent inhabitants all suffer from malarial cachexia,
and where the field-labourers, who come from healthy parts of
Italy to reap the harvest, after a short time all contract fever.
This fever-haunted spot is in the King of Italy's hunting-ground
near Ostia, at the mouth of the Tiber. It is waterlogged and
jungly, and teems with insect life. The only protection employed
against mosquito-bite and fever by the experimenters who occupied
this hut was mosquito-netting, wire screens in doors and windows,
and, by way of extra precaution, mosquito-nets round their beds.
Not a grain of quinine was taken. They go about the country quite
freely--always, of course, with an eye on _Anopheles_--during the
day, but are careful to be indoors from sunset to sunrise. Up to
21st September, the date of Dr. Sambon's last letter to me, the
experimenters and their servants had enjoyed perfect health, in
marked contrast to their neighbours, who were all of them either
ill with fever, or had suffered malarial attacks."

A similar "experiment," of the utmost importance, was made in 1900 by Professor Grassi. It concerned the workmen and their families along the Battipaglia-Reggio railway, 104 in all, including 33 children. The great majority of them had suffered from malaria in the preceding year; and only 11, including 4 children, had never suffered from it. Pending the arrival of the malarial season, quinine was given to all who needed it. The first _Anopheles_ with its salivary glands infected was found on 14th June. Twelve days later came a case of malaria outside the "zone of experiment," in a person who had never had malaria before. The twelve days correspond to the incubation-period after infection. _Anopheles_ having come, and the malarial season with him, the experiment was begun. The houses were carefully protected with wire netting, chimneys and all; the _siesta_ was taken under wire netting; the workmen, if they were out in the evening or at night, wore veils and gloves; and _Anopheles_ was to be killed wherever he was found. Quinine was altogether given up and forbidden, except for three workmen who had escaped or evaded its use before June, and had, indeed, never before been treated with quinine; one of them, moreover, had been sleeping outside the zone of experiment in July. Except these three, all the 104 and their doctors remained absolutely free from malaria up to 16th September, the date of Professor Grassi's report:--

"Rightly to estimate the value of these facts, it is necessary
briefly to describe the surroundings of the protected area.
Towards the north, coming from Battipaglia, three railway
cottages are situated, at a distance of 1, 2, and 3 kilometres
respectively. The 25 inhabitants of these cottages, although
they were put under the tonic and quinine treatment in the
non-malarial season, all without exception were taken ill with
malarial fevers, in many cases obstinate."

Experiments of voluntary exposure to bite from an infected mosquito were made at or about this time, in London, New York, Italy, and India. The London "consignment" of mosquitoes had been allowed to bite a malaria-patient in Rome. The experiment had to be very carefully planned:--

"To have sent mosquitoes infected with malignant tertian
parasites might have endangered the life of the subject of the
experiment; and quartan-infected insects might have conferred a
type of disease which, though not endangering life, is extremely
difficult to eradicate. The cases, therefore, on which the
experimental insects were fed had to be examples of pure benign
tertian--a type of case not readily met with in Rome during the
height of the malarial season; the absolute purity of the
infection could be ascertained only by repeated and careful
microscopic examination of the blood of the patient." (_British
Medical Journal_, 29th September 1900.)

The mosquitoes were forwarded, through the British Embassy in Rome, to the London School of Tropical Medicine. The two brave gentlemen who let themselves be bitten by some thirty of the mosquitoes were in due time attacked by malaria, and the tertian forms of the parasite were found in their blood. Nine months later, one of them had a relapse, and the parasite was again found in his blood.

It is not possible to sum up the wealth of work on malaria published in 1900-1901. Good accounts of it are in the Transactions of the Section of Tropical Diseases, at the Annual Meeting of the British Medical Association (Cheltenham, 1901), and in the Thompson Yates Laboratories Reports, vol. iii., pt. 2, 1901. Everything had to be studied: not only the nature and action of the _plasmodium_ in all its phases, but also the whole natural history and habits of the _Anopheles_ of different countries; and, above all, the incidence of the disease on natives and on Europeans in China, India, and Africa. All that can be done here is to try to indicate the principal lines followed in the present world-wide campaign against malaria. The following paragraphs are taken mostly from the accounts given by Dr. Christophers and Dr. Annett, in the Thompson Yates Laboratories Report, 1901:--

1. _Elimination of the Infection at its Source._ This is the method employed with success by Professor Koch in New Guinea, viz., to search out all cases of malaria (the concealed ones in particular), and to render them harmless by curing them with quinine. At Stephansort, by thus hunting up all infected cases, and as it were, sterilising them by the systematic administration of quinine, he was able to achieve a great reduction of the disease in the next malarial season, even under adverse conditions. He says, in his report to the German Government: "The results of our experiment, which has lasted nearly six months, have been so uniform and unequivocal that they cannot be regarded as accidental. We may assume that it is directly owing to the measures we have adopted that malaria here has, in a comparatively short time, almost disappeared."

This method, of course, is applicable only in small communities; and, within these limits, it may become one of the most valuable of all methods, being, like the quality of mercy, a blessing both to him who gives and to him who taketh. But it cannot be practised on a vast scale. This difficulty is well put by Sir William MacGregor, K.C.M.G., Governor of Lagos, West Africa:--

"In all probability, the day will come before long, when
newly-appointed officers for places like Lagos will have to
undergo a test as to whether they can tolerate quinine or not. A
man that cannot, or a man that will not, take quinine, should
not be sent to or remain in a malarial country, as he will be
doing so at the risk of his own life, _and to the danger of
others_.... The great difficulty is how to extend this treatment
beyond the service, more particularly to the uneducated masses
of the natives. It is simply impossible to protect the whole
population by quinine administered as a prophylactic. In the
first place, the great mass of natives would not take the
medicine; and, in the second place, the Government could not
afford to pay for the 70 tons of quinine a year that would be
required to give even a daily grain dose to each of 3,000,000 of
people."

2. _Segregation of Europeans from Natives._ This method is strongly advocated by the members of the Nigeria Expedition of the Liverpool School (1900). The distance of removal to half a mile is considered sufficient: "Considerable evidence has now been accumulated to prove that the distance which is traversed by a mosquito is never very great, and extremely rarely reaches so much as half a mile." The arguments in favour of this method of "segregation" are of so great interest that they must be put here at some length. The drawback is that the method cannot be followed everywhere to its logical issue without some risk of giving offence, of seeming to abandon the native, of damaging commerce, and so forth. But, short of this, much might be done for the protection of Europeans in Africa:--

"This method is a corollary of the discovery that native
children in Africa practically all contain the malaria parasite,
and are the source from which Europeans derive malaria. Koch
showed in New Guinea that in most places infection was very
prevalent in native children, so much so that in some villages
100 per cent. of those examined contained parasites. He also
showed that, as the children increased in age, immunity was
produced, so that in the case of adults a marked immunity was
present, and malarial infection was absent. The Malaria
Commission showed, independently, that a condition of universal
infection existed among the children of tropical Africa,
associated with an immunity of the adults. This infection in
children had many remarkable characteristics. The children were
in apparent health, but often contained large numbers of
parasites, and a small proportion only of the children failed to
show some degree of infection.... The Liverpool School
Expedition found a similar condition of affairs in all parts of
Nigeria visited by them.

"With a knowledge of the ubiquity of native malaria, the method
of infection of Europeans becomes abundantly clear. The reputed
unhealthiness or healthiness of stations is seen at once to be
dependent on the proximity or non-proximity of native huts. The
attack of malaria after a tour up-country, the malaria at
military stations like Prah-su, the abundance of malaria on
railways, are all explicable when the extraordinary condition of
universal native infection is appreciated. It is evident that,
could Europeans avoid the close proximity of native huts, they
would do away with a very obvious and great source of
infection.... When it is understood that each of these huts
certainly contains many children with parasites in their blood,
and also scores or hundreds of _Anopheles_ to carry the
infection, then the frequency with which Europeans suffer from
malaria is scarcely to be wondered at.... The accompanying plan
is that of a new railway settlement on the Sierra Leone Railway.
Miles of land free from huts exist along the line, but the close
neighbourhood of native huts has been selected. At the time of
building of these quarters, it lay in the power of the engineers
to have a malaria-free settlement; instead of which, by the
non-observance of a simple fact, the station is most malarious:
in this particular instance, much ingenuity has been shown in
providing each set of European quarters with plenty of malarial
infection. In towns only is there any difficulty in carrying out
the principle of segregation. In two instances, however, this
has been carried out in towns, with the result that the
segregated communities of Europeans are notoriously the most
healthy on the West Coast. Even when no scheme of complete
segregation can be carried out, the principle should always be
borne in mind, and, whenever opportunity offers, huts should be
removed, and European houses built in the open.... It is almost
universally the rule in West Africa to find European houses
built round by native quarters, a practice which long experience
in India has taught Europeans to avoid carefully. At Old
Calabar, many of the factories are almost surrounded, except in
front, by native habitations; similarly, at Egwanga, the small
native town is built by the side and back of one of the
factories. Also at the Niger Company's factory at Lokoja, the
native houses are very close up to the Company's boundary
railings. Akassa engineers' quarters may be, again, mentioned as
an example where the engineering artisans, chiefly natives of
Lagos, Accra, and Sierra Leone, are housed with their families
alongside the European house. A large proportion of these native
children were found by us to contain malarial parasites.
Similarly also at Asaba, the proximity of the barracks of the
Hausa soldiers, who have their wives and children with them, is
a dangerous menace to the officers at the Force House.

"Examples of the opposite condition of affairs might also be
given. For instance, at Old Calabar, the Government offices and
Consulate, Vice-Consulate, and medical house, are comparatively
free from malarial fever; it having been established that the
natives shall not build on the European side of the creek
separating the two slopes on which the native town and European
quarters are built. This creek is at a distance of about half a
mile from the houses mentioned."

It is plain, from these and other instances given by the members of the Nigeria Expedition, that a modified sort of "segregation" can be effected in many places, without any injury either to native feelings, or to politics, or to commerce; and that by such segregation the risk of malaria among Europeans in Africa would be diminished.

3. _Protection against Anopheles._ Manson, in his _Tropical Diseases_ (1905), says, "The question is often asked, Is there any other way by which malaria can be contracted than through a mosquito-bite? For many reasons, I believe not. It is difficult to prove a negative; but, so far, there is no observation capable of bearing investigation that would lead us to suppose that malaria can be acquired, under natural conditions, except by mosquito-bite," All authorities are agreed that, practically, the fight against malaria and the fight against _Anopheles_ are one and the same thing; and the experiments by Sambon, Low, and Grassi, show what can be done, in this war against the mosquito, by way of defence. But what is practicable in Italy might not be generally practicable on the West African coast; as Sir William MacGregor says of Lagos:--

"It is not likely that in a place like Lagos as good results can
be obtained from the use of mosquito-proof netting as in Italy.
One great objection to it here is the serious and highly
disagreeable way it checks ventilation. This is a difficulty
that cannot be fully brought home to one in a cold climate. But,
in a low-lying, hot, and moist locality like Lagos, it comes to
be a choice of evils, to sit inside the netting stewed and
suffocated, or to be worried and poisoned by mosquitoes outside.
The netting is hardly a feasible remedy as regards native
houses. It is not possible to protect even European quarters
completely by it. Few officers or others are so occupied that
they could spend the day in a mosquito-proof room. Certain it is
that any man that suffers from the singular delusion that
mosquitoes bite only during the night, would have a speedy cure
by spending a few days, or even a few hours, in Lagos.
Operations here (September 1901) are being limited to supplying
one mosquito-proof room to the quarters of each officer. In this
he will be able to spend the evening free from mosquitoes if he
chooses to do so. The European wards of the hospital are
similarly protected."

The European in Africa, as Ross says, is generally neglectful of his health; and the "unhealthiness" of the African coast is to some extent due to the life that men lead there:--

"Let us compare the habits of a European in a business-house in
Calcutta with the habits of a European in West Africa. In
Calcutta he sleeps under a punkah or mosquito-net, or both; he
dresses and breakfasts under a punkah; in the evening he takes
vigorous exercise, and he dines under a punkah. He wears the
lightest possible clothing, he lives in a solid, cool, airy
house, and he obtains very good food; once in five or six years,
he returns to Europe for leave.... In Africa, the houses are
frequently very bad; in Freetown, for instance, they are the
same as the houses of natives, and are mingled with them. The
Anglo-African seems to imagine that he can live in the tropics
in the same manner as he lives in England. He seldom uses a
punkah, except perhaps for an hour at dinner-time, and, not
seldom, he neglects even the mosquito-net. The food is often, or
generally, execrable. Owing to the frequent absence of gymkhanas
and clubs, the exile obtains little suitable exercise."

But whatever risks the old resident may choose to take, the newcomer can at least use a proper and efficient mosquito-net at night, and avoid sleeping in a native house, and protect himself in these and the like ways against malaria.

4. _The keeping down of Anopheles._ The breeding places of _Anopheles_ are ponds, swamps, and puddles, roadside ditches, tanks, and cisterns, old disused canoes, and the like collections of stagnant water: also the smaller receptacles that are more generally occupied by _Culex_, such as broken bottles, old tins, pots, and calabashes, and barrels, whatever will hold water--all the débris and broken rubbish round huts or houses. In all these places, _Anopheles'_ eggs or larvæ are found; and, with practice, it is easy to detect them. Of course, it is not easy to wage war against the adult mosquito: the work is, _Venienti occurrere morbo_, to organise gangs of workmen, or of prison labour, and "mosquito brigades"; to clear the ground of cartloads of old biscuit-tins, broken gin-bottles, and other dust-heap things, in and around the place; to cover-in the cisterns, rain-barrels, and wells; to clean pools and duck-ponds of weed, and stock them with minnows; to put a film of kerosene to the puddles, or sweep them out, or fill them up and turf them over; everywhere, to drain, and level, and clean-up the surface soil; and everywhere, by these and the like methods, to break the cycle of the life of the _plasmodium malariæ_:--

"Draining and cultivation where the land will repay the
expenditure, permanent and complete flooding where it will not,
and such flooding is possible; proper paving of unhealthy towns,
and the filling-in of stagnant, swampy pools; these--in other
words, all measures calculated to keep down mosquitoes--are the
more important things to be striven for in attempting the
sanitation of malarious districts. In England, in Holland, in
France, in Algeria, in America, and in many other places,
enormous tracts of country, which formerly were useless and
pestilential, have been rendered healthy and productive by such
means." (Manson.)

And, short of such great enterprises as Government works of drainage, much has already been done, in many African towns, and in India, by the work of a few men and women: not only by practical sanitary improvements, but by insistent teaching and lecturing. For the admirable results recently obtained in Ismailia, Algeria, Formosa, and the Malay States, see the _Medical Annual_, 1905 and 1906.[39]

[39] This paper, by Dr. Stephens, gives also the reasons why
equally good results were not obtained at Mian Mir, Punjab. The
whole paper is of great interest.

Before leaving the subject of malaria, it must be added that the discovery and study of the parasite which causes it have cleared up the mystery of the specific action of quinine upon the disease. It operates simply by its germicidal effect upon the microbe. But, beyond this, we have now a clue which we never had before to guide us to the most advantageous manner of administering the drug.

2. YELLOW FEVER

The specific organism of malaria may become active again and again in the blood, causing relapses twenty years or more after the original infection. The specific organism of yellow fever expends itself at once, in one acute attack; and, if the patient recovers, he is thenceforth more or less immune against infection. That the inoculation of the disease, by the application of a single mosquito recently contaminated, is calculated to produce a mild or abortive attack less dangerous than the average attack among the non-acclimatised, was known to Finlay, and was confirmed in 1899 by the Army Commission of the United States.

Of the mortality of the disease, Sir Patrick Manson, in 1900, wrote as follows:--