Use of culicides, oiling ponds, etc.

Drainage and scavenging to destroy breeding places.

Enforcement of penalties for harboring larvae or keeping stagnant water.

Educational methods.

4. Systematic treatment with quinine to exterminate the parasites.

MOSQUITOES AND YELLOW FEVER

Yellow fever was until recently one of the most dreaded of epidemic diseases. It is an acute, specific and infectious disease, non-contagious in character but occurring in epidemics, or endemics, within a peculiarly limited geographical area. It is highly fatal, but those who recover are generally immune from subsequent attacks.

It is generally regarded as an American disease, having been found by Cortez, in Mexico, and being confined princ.i.p.ally to the American continents and islands. It also occurs in Africa and attempts have been made to show that it was originally an African disease but there is not sufficient evidence to establish this view.

There have been many noted outbreaks in the United States. Boston suffered from it in 1691 and again in 1693; New York in 1668 and as late as 1856; Baltimore in 1819. In 1793 occurred the great epidemic in Philadelphia, with a death rate of one in ten of the population. In the past century it was present almost every year in some locality of our Southern States, New Orleans being the greatest sufferer. In the latter city there were 7848 deaths from the disease in 1853, 4854 in 1858, and 4046 in 1878. The last notable outbreak was in 1905. Reed and Carroll (1901) estimated that during the period from 1793 to 1900 there had not been less than 500,000 cases in the United States.

[Ill.u.s.tration: 130. Anopheles quadrimaculatus, male and female, (3). After Howard.]

As in the case of the plague, the most stringent methods of control proved ineffective and helplessness, almost hopelessness marked the great epidemics. A vivid picture of conditions is that given by Mathew Cary, 1793 (quoted by Kelly, 1906) in "A Short Account of the Malignant Fever Lately Prevalent in Philadelphia."

[Ill.u.s.tration: 131. Anopheles punctipennis. Female, (4). After Howard.]

"The consternation of the people of Philadelphia at this period was carried beyond all bounds. Dismay and affright were visible in the countenance of almost every person. Of those who remained, many shut themselves in their houses and were afraid to walk the streets. * * *

The corpses of the most respectable citizens, even those who did not die of the epidemic, were carried to the grave on the shafts of a chair (chaise), the horse driven by a negro, unattended by friends or relative, and without any sort of ceremony. People hastily shifted their course at the sight of a hea.r.s.e coming toward them. Many never walked on the footpath, but went into the middle of the streets to avoid being infected by pa.s.sing by houses wherein people had died. Acquaintances and friends avoided each other in the streets and only signified their regard by a cold nod. The old custom of shaking hands fell into such disuse that many shrunk back with affright at even the offer of the hand. A person with a c.r.a.pe, or any appearance of mourning was shunned like a viper. And many valued themselves highly on the skill and address with which they got to the windward of every person they met. Indeed, it is not probable that London, at the last stage of the plague, exhibited stronger marks of terror than were to be seen in Philadelphia from the 24th or 25th of August until pretty late in September."

[Ill.u.s.tration: 132. Anopheles crucians. Female (4). After Howard.]

Such was the condition in Philadelphia in 1793 and, as far as methods of control of the disease were concerned, there was practically no advance during the last century. The dominant theory was that yellow fever was spread by _fomites_, that is, exposed bedding, clothing, baggage, and the like. As late as 1898 a bulletin of the United States Marine Hospital Service stated:

"While yellow fever is a communicable disease, it is not contagious in the ordinary acceptance of the term, but is spread by the infection of places and articles of bedding, clothing, and furniture."

Based upon this theory, houses, baggage, freight, even mail, were disinfected, and the most rigid quarantine regulations were enforced.

The hardships to which people of the stricken regions were subjected and the financial losses are incalculable. And withal, the only efficient check upon the disease seemed to be the heavy frosts. It was found that for some reason, the epidemic abated with cold weather,--a measure beyond human control.

[Ill.u.s.tration: 133. Culex sollicitans. Female (4). After Howard.]

It is not strange that among the mult.i.tude of theories advanced to explain the cause and method of dissemination of the disease there should be suggestions that yellow fever was transmitted by the mosquito.

We have seen that Beauperthuy (1855) clearly urged this theory.

More detailed, and of the greatest influence in the final solution of the problem were the arguments of Dr. Carlos Finlay, of Havana. In 1881, in a paper presented before the "Real Academia de Ciencias Medicas, Fisicas y Naturales de la Habana," he said:

"I feel convinced that any theory which attributes the origin and the propagation of yellow fever to atmospheric influences, to miasmatic or meteorological conditions, to filth, or to the neglect of general hygienic precautions, must be considered as utterly indefensible."

He postulated the existence of a material transportable substance causing yellow fever,--"something tangible which requires to be conveyed from the sick to the healthy before the disease can be propagated" and after discussing the peculiarities of the spread of the disease and the influence of meteorological conditions, he decides that the carriers of the disease must be sought among insects. He continues:

"On the other hand, the fact of yellow fever being characterized both clinically and (according to recent findings) histologically, by lesions of the blood vessels and by alterations of the physical and chemical conditions of the blood, suggested that the insect which should convey the infectious particles from the patient to the healthy should be looked for among those which drive their sting into blood vessels in order to suck human blood. Finally, by reason of other considerations which need not be stated here, I came to think that the mosquito might be the transmitter of yellow fever."

"a.s.similating the disease to small-pox and to vaccination, it occurred to me that in order to inoculate yellow fever it would be necessary to pick out the inoculable material from within the blood vessels of a yellow fever patient and to carry it likewise into the interior of a blood vessel of a person who was to be inoculated. All of which conditions the mosquito satisfies most admirably through its bite."

In the course of his study of the problem, Finlay made detailed studies of the life history and habits of the common mosquitoes at Havana, and arrived at the conclusion that the carrier of the yellow fever was the _Culex mosquito_ or _Aedes calopus_, as it is now known. With this species he undertook direct experimental tests, and believed that he succeeded in transmitting the disease by the bite of infected mosquitoes in three cases. Unfortunately, possibility of other exposure was not absolutely excluded, and the experiments attracted little attention.

Throughout the next twenty years Finlay continued his work on yellow fever, modifying his original theory somewhat as time went on. Among his later suggestions was that in the light of Smith"s work on Texas fever, his theory must be "somewhat modified so as to include the important circ.u.mstance that the faculty of transmitting the yellow fever germ need not be limited to the parent insect, directly contaminated by stinging a yellow fever patient (or perhaps by contact with or feeding from his discharges), but may be likewise inherited by the next generation of mosquitoes issued from the contaminated parent." He believed that the bite of a single mosquito produced a light attack of the disease and was thus effective in immunizing the patient. Throughout the period, many apparently successful attempts to transmit the disease by mosquitoes were made. In the light of present day knowledge we must regard these as defective not only because possibility of other infection was not absolutely excluded but because no account was taken of the incubation period within the body of the mosquito.

In 1900, while the American army was stationed in Cuba there occurred an epidemic of yellow fever and an army medical board was appointed for "the purpose of pursuing scientific investigations with reference to the acute infectious diseases prevalent on the island." This was headed by Walter Reed and a.s.sociated with him were James Carroll, Jesse W. Lazear and Aristides Agramonte, the latter a Cuban immune. For a detailed summary of this work the lay reader cannot do better than read Dr.

Kelly"s fascinating biography "Walter Reed and Yellow Fever."

Arriving at the army barracks near Havana the Commission first took up the study of _Bacillus icteroides_, the organism which Sanarelli, an Italian physician, had declared the causative agent in yellow fever.

They were unable to isolate this bacillus either from the blood during life or from the blood and organs of cadavers and therefore turned their attention to Finlay"s theory of the propagation of yellow fever by means of the mosquito. In this work they had the unselfish and enthusiastic support of Dr. Finlay himself, who not only consulted with them and placed his publications at their disposal, but furnished eggs from which their experimental mosquitoes were obtained. Inoculations of eleven non-immunes through the bite of infected mosquitoes were made, and of these, two gave positive results. The first of the two was Dr. Carroll who allowed himself to be bitten by a mosquito which had been caused to feed upon four cases of yellow fever, two of them severe and two mild.

The first patient had been bitten twelve days before.

Three days after being bitten, Dr. Carroll came down with a typical case of yellow fever. So severe was the attack that for three days his life hung in the balance. During his convalescence an incident occurred which showed how the theory of mosquito transmission of the disease was generally regarded. We quote from Dr. Kelly: "One of his nurses who came from Tennessee had had considerable experience with yellow fever, having indeed, lost her husband and several children from it. One day early in his illness Dr. Carroll mentioned to her that he had contracted the disease through the bite of a mosquito, and noticed that she looked surprised. Some time later, when well enough to look over the daily records of his condition, he found this entry: "Says he got his illness through the bite of a mosquito,--delirious"."

The second case was that of an American who was bitten by four mosquitoes, two of which had bitten severe (fatal) cases of yellow fever twelve days previously, one of which had bitten a severe case (second day) sixteen days before and one which had bitten a severe case eight days before. Five days later, the subject developed a well p.r.o.nounced but mild case of the disease.

In the meantime, another member of the Commission, Dr. Lazear, was accidentally bitten by a mosquito while collecting blood from yellow fever patients. Five days later he contracted a typical case which resulted fatally.

So clear was the evidence from these preliminary experiments that the commission felt warranted in announcing, October 27, 1900, that, "The mosquito serves as the intermediate host for the parasite of yellow fever, and it is highly probable that the disease is only propagated through the bite of this insect."

In order to extend the experimental evidence under conditions which could leave no possibility of infection from other sources, a special experimental sanitary station, named in honor of the deceased member of the Commission, was established in an open field near the town of Quemados, Cuba. Here there were constructed two small buildings known respectively as the "infected clothing building" and the "infected mosquito building."

The infected clothing building, 14 20 feet in size, was purposely so constructed as to exclude anything like efficient ventilation, but was thoroughly screened to prevent the entrance of mosquitoes. Into this building were brought sheets, pillow-slips, blankets, etc., contaminated by contact with cases of yellow fever and their discharges,--many of them purposely soiled with a liberal quant.i.ty of black vomit, urine, and fecal matter from patients sick with yellow fever. Nothing could better serve as the fomites which were supposed to convey the dread disease.

Three non-immunes unpacked these articles, giving each a thorough handling and shaking in order to disseminate through the air of the room the specific agent of the disease. They were then used in making up the beds which the volunteers occupied each night for a period of twenty days. The experiment was repeated three times, volunteers even sleeping in the soiled garments of yellow fever victims but in not a single case was there the slightest symptom of disease. The theory of the spread of yellow fever by fomites was completely demolished.

The infected mosquito building, equal in size to its companion, was the ant.i.thesis as far as other features were concerned. It was so constructed as to give the best possible ventilation, and bedding which was brought into it was thoroughly sterilized. Like the infected clothing building it was carefully screened, but in this case it was in order to keep mosquitoes in it as well as to prevent entrance of others.

Through the middle of the room ran a mosquito-proof screen.

On December 5, 1900, a non-immune volunteer who had been in the quarantine camp for fifteen days and had had no other possible exposure, allowed himself to be bitten by five mosquitoes which had fed on yellow fever patients fifteen or more days previously. The results were fully confirmatory of the earlier experiments of the Commission--at the end of three days, nine and a half hours, the subject came down with a well marked case of yellow fever.

In all, ten cases of experimental yellow fever, caused by the bite of infected mosquitoes were developed in Camp Lazear. Throughout the period of the disease, other non-immunes slept in the little building, separated from the patient only by the mosquito-proof screen, but in no circ.u.mstances did they suffer any ill effects.

It was found that a yellow fever patient was capable of infecting mosquitoes only during the first three or four days after coming down with the disease. Moreover, after the mosquito has bitten such a patient, a period of at least twelve days must elapse before the insect is capable of transmitting the disease.

Once the organism has undergone its twelve day development, the mosquito may remain infective for weeks. In experiments of the Commission, two of the mosquitoes transmitted the disease to a volunteer fifty-seven days after their contamination. No other volunteers presenting themselves, one of these mosquitoes died the sixty-ninth and one the seventy-first day after their original contamination, without it being determined whether they were still capable of transmitting the disease.

So carefully carried out was this work and so conclusive were the results that Dr. Reed was justified in writing:

"Six months ago, when we landed on this island, absolutely nothing was known concerning the propagation and spread of yellow fever--it was all an unfathomable mystery--but today the curtain has been drawn--its mode of propagation is established and we know that a case minus mosquitoes is no more dangerous than one of chills and fever."

The conclusions of the Commission were fully substantiated by numerous workers, notably Dr. Guiteras of the Havana Board of Health, who had taken a lively interest in the work and whose results were made known in 1901, and by the Brazilian and French Commission at Sao Paulo, Brazil, in 1903.

Throughout the work of the Army Commission and down to the present time many fruitless efforts have been made to discover the specific organism of yellow fever. It was clearly established that the claims of Sanarelli for _Bacillus icteroides_ were without foundation. It was found, too, that whatever the infective agent might be it was capable of pa.s.sing through a Berkefeld filter and thus belongs to the puzzling group of "filterable viruses." It was further found that the virus was destroyed by heating up to 55 C for ten minutes. It is generally believed that the organism is a Protozoan.

The question of the hereditary transmission of the yellow fever organism within the mosquito was left unsettled by the Army Commission, though, as we have seen, it was raised by Finlay. Marchoux and Simond, of the French Commission devoted much attention to this phase of the problem and basing their conclusions on one apparently positive case, they decided that the disease could be transmitted through the egg of an infected _Aedes calopus_ to the second generation and thence to man. The conclusion, which is of very great importance in the control of yellow fever, has not been verified by other workers.

Once clearly established that yellow fever was transmitted solely by mosquitoes, the question of the characteristics, habits, and geographical distribution of the insect carrier became of vital importance.

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