Tropical Diseases/Chapter 13
CHAPTER XIII
YELLOW FEVER
Definition.— An acute, specific, very fatal febrile disease occurring epidemically, or as an endemic, within a peculiarly limited geographical area. Though subject to great variations, its typical clinical manifestation may be said to be characterized by a definite course consisting of an initial stage of a sthenic nature, rapidly followed by an adynamic condition in which such evidences of blood destruction as black vomit, albuminuria, and hæmatogenous jaundice are liable to occur. One attack generally confers permanent immunity. The germ is transmitted by the domestic mosquito, Stegomyia calopus (S. fasciata).
Geographical distribution.— Of all the important zymotic diseases, yellow fever has the most restricted geographical range. Its centre is the West Indies, whence it spreads north to the United States and Mexico; south to the Brazils and, at times, as far as Buenos Ayres and Monte Video; west to Central America, and across the Isthmus of Panama to the Pacific coast, along which it extends north to the Gulf of California and south to Peru. It occurs also, in epidemic form, on the West Coast of Africa, where it appears to be endemic. It is impossible to determine from existing records whether yellow fever was originally an African or a West Indian disease.
Yellow fever has been imported frequently into Portugal and Spain, and once from Spain into Italy. Although a good many died in these visitations, the disease has never obtained a permanent footing in Europe. Cases have occurred in seaport towns in France and Great Britain - Brest and Swansea, for example; invariably, however, these little epidemics have died out.
In several of the West India Islands yellow fever is endemic. Until recently it was always to be found in Havana. Formerly the Brazils enjoyed an absolute immunity; but from 1849, when yellow fever was introduced for the first time into Bahia by a ship from New Orleans, it was practically endemic in the large cities until the institution of anti-stegomyia measures recently. At Rio de Janeiro, although in some years the cases were few, it was never entirely absent. It is still very common in Manaos. In such places as New Orleans, Charleston, Monte Video, and Buenos Ayres, although now and again epidemics of great severity break out, several years may pass without its appearing. Some of these epidemic visitations bring a heavy death-bill; thus, in New Orleans, in 1853, 7,970 people died of yellow fever; in 1867, 3,093. In Rio, in 1850, it claimed 4,160 victims; in 1852, 1,943; and in 1886, 1,397. In Havana the annual mortality from this cause used to range from 500 to 1,600 or over.
Epidemiology.— Influence of atmospheric temperature.— The histories of these and other epidemics show that the virus of yellow fever can be transported from one place to another, and that for its development in epidemic form it requires an atmospheric temperature of over 75° F. It ceases to spread when the thermometer sinks below this point, and it stops abruptly as an epidemic when the freezing-point is reached. Dampness favours yellow fever; it is therefore most prone to occur and to spread during the rainy season.
Usually a sea-coast disease.— The favourite haunts of the disease are the sea-coast towns, the banks of rivers, and flat delta country. Rarely does it pass far inland, or ascend high ground. Still, there have been exceptions to this general rule; for yellow fever has been found far inland, and at a considerable elevation (Sao Paulo, Brazil, 2,500 feet; Newcastle, Jamaica, 3,000-4,000 feet; Cuzco, Peru, 9,000-10,000 feet). Villages are seldom affected; nor does the disease readily spread if introduced into rural localities. In spreading inland it follows the lines of communication railways, canals, navigable rivers. A ship disease.— Ship epidemics were common occurrences formerly. The ideal haunt of yellow fever is the low-lying, hot, squalid, insanitary district in the neighbourhood of the wharfs and docks of large seaport towns.
A place disease.— It is, in a sense, a place disease like malaria. That is to say, if the patient be removed to a hitherto unaffected spot, his attendants and neighbours will not contract the disease, unless the spot itself first become infected. The occurrence of this place infection will depend on whether the particular locality affords in sufficient numbers the appropriate intermediary— the stegomyia mosquito— for the transmission of the germ brought by the patient. If the locality supplies this condition, then, for the time being, the disease will spread and become epidemic; if the locality does not supply this condition, then the disease will not spread. It is safe, therefore, to visit a yellow fever patient if he is lodged outside the endemic or epidemic area; but it is never safe for the susceptible to visit the endemic area, whether they come into direct contact with the sick or not.
Immunity acquired by prolonged residence or by a previous attack.— A well-established fact about yellow fever is that the natives of, and those who have lived for a long time in, the endemic area are practically immune from the disease; or, if they are attacked, the disease is usually of a very mild type. It is also said that if the native quits the endemic area his immunity decreases in proportion to the length of time he remains away; so that, after long absence, on his return to the endemic area he may be attacked just as an ordinary visitor might be. Further, those who enter the endemic area for the first time are the most susceptible, the susceptibility decreasing with length of residence. It has been inferred from this, perhaps —but not certainly— correctly, that at such places as Rio and Havana the endemicity of the disease was kept up by the continual influx of foreign and, therefore, susceptible visitors.
Race as influencing susceptibility.— Formerly it was believed that the negro is little liable to yellow fever, and that when he gets it the attack is usually mild; and also that the yellow-skinned races are more susceptible than the negro, but less so than the European. It was also said that the susceptibility of the European increases in proportion to the height of the latitude of his native place; that is, the Norwegian is more susceptible than the Frenchman, and the Frenchman more than the Italian or the Spaniard. The facts on which this belief was founded may admit of another and more rational explanation than that of varying degrees of racial susceptibility; relative racial susceptibility may be more a matter of racial opportunity than of colour of skin. We now know that the negro from a non-endemic place—Barbados, for example— is just as liable as the European to an attack of yellow fever should he visit an endemic or epidemic area.
Incubation period.— The incubation period of yellow fever rarely exceeds four or five days; it may, it is said, be much shorter— under twenty-four hours. The limits, according to Bérenger-Féraud, are one to fifteen days in the temperate zones, one to thirty days in the tropics. Precise experiments indicate an average incubation of from three to five days, and an extreme limit of thirteen days. Occasionally it happens that the disease breaks out in a ship after she has been several weeks at sea, having had no communication with the land or with another ship in the meantime. The rationale of this, and also of the prolonged incubation periods formerly assigned by writers to the disease, we now understand. It must not be inferred from these ship epidemics that the incubation period is to be reckoned in weeks. Infected mosquitoes may have been in the ship from the time she left port, but the crew may not have been bitten and infected until long afterwards.
Incubation period preceding epidemic extension.— It has been observed that a period of at least a fortnight elapses between the arrival of a yellow-fever patient in a hitherto uninfected district and the occurrence of the first case of the epidemic he may give rise to. That is to say, that although, as stated above, the incubation period of yellow fever— the period elapsing between the introduction of the virus into the body and the on-coming of fever— is usually only from three to five days, yet a period of at least twelve days must elapse before that virus, after removal from one human body, can be effectively implanted in another human body. What becomes of it during these twelve days? The answer to this question has now been supplied, and with it the key to most of the epidemiological peculiarities of yellow fever.
Duration of the infective period.— This is singularly brief. A yellow-fever patient is dangerous to his neighbours only during the first three or four days of the disease. After this he cannot confer infection.
The germ.— A great many attempts have been made to discover the germ or virus of yellow fever, and a corresponding variety of organisms have been described. In the belief that some of these were the true germs, certain bacteriologists went the length of practising protective inoculation with attenuated cultures of their respective organisms, whilst others elaborated curative sera on the orthodox lines. Both sets of enthusiasts have claimed successes. We now know, however, that the germ of yellow fever is not a bacterium, at all events is not a visible bacterium, and that it cannot be cultivated or modified on the ordinary bacteriological lines. Freire's Cryptococcus xanthogenicus, Finlay's Tetragenus febris flava, and Sanarelli's Bacillus icteroides have no longer anything but an historical interest.
At the instigation of the Government of the United States, these and other organisms were rigidly investigated by Sternberg, whose standing as a bacteriologist and whose judicial cast of mind eminently qualified him for forming a trustworthy judgment. His verdict on them, and on many similar organisms for which pathogenic claims had been advanced, was unfavourable.
Seidelin has recently described certain very minute and somewhat indefinite supposed bodies in the red blood-corpuscles in yellow fever, which he has named Paraplasma flavigenum, and which he regards as the germ of the disease. So far, this claim has not been accepted by yellow-fever experts, and is not supported by convincing experimental evidence.
Nature of the yellow - fever germ indicated by epidemiology.— In earlier editions of this book I remarked, " The reasons for the peculiar geographical limitation of yellow fever are but partially understood. A principal reason, undoubtedly, is that yellow fever belongs to a somewhat restricted class of diseases which, though communicable, are not directly so through immediate conduction from sick to sound; diseases whose germs do not pass quickly from the sick to the healthy, like those of scarlatina and smallpox, but have first, apparently, to undergo extracorporeally developmental changes that enable them to attack and to live in the human body. Such diseases, seeing that their propagation demands an additional condition— the extracorporeal state or medium— must necessarily be more difficult to acquire, must spread more slowly, and be more limited geographically, than the ordinary infectious diseases." These remarks, suggested by the peculiar epidemiological features of yellow fever, have received remarkable confirmation from the brilliant work of Reed, Carroll, Agramonte, and Guiteras, and by many subsequent workers.
The germ occurs in the blood.— This has been incontestably demonstrated by Reed, Carroll, and Agramonte. They injected into six non-immunes blood from yellow-fever patients. In this way, in five instances, they conferred the disease within the recognized limits of the incubation period. In another experiment they induced yellow fever by injection of defibrinated blood. By other experiments they showed that the virulence of the blood was destroyed by a temperature of 55° C. Another point, already alluded to, is that these experiments, taken in conjunction with others to be presently described, showed that the germ is present in the blood, at all events in a transferable state, only during the first three or four days of the disease. Yet another point these experimenters sought to establish, viz. that this phase of the yellow -fever germ is so minute that it can pass through a Berkefeld filter. Further, that blood from a yellow -fever infection produced by injection of filtered serum will, on being injected into another non-immune, again confer the disease; proving that the virus so conveyed was capable of multiplying— that is to say, that it is not a toxin or chemical body merely, but that it is a living germ. These latter inferences are deduced from what was practically only one experiment. Although the evidence, therefore, is somewhat meagre, yet, considering the high order of the other work accomplished in the same field by these American and subsequent observers, we are almost justified in concluding with them that, like the germ of rinderpest, of horse-sickness, and of foot-and-mouth disease, at least one phase of the yellow-fever germ as it exists in the blood, though particulate, is ultramicroscopic.
The mosquito the intermediary and diffusing agent of the germ of yellow fever.— Having satisfied themselves by direct observations, and by a long series of carefully conducted culture experiments on the blood, that the germ of yellow fever was not of an ordinary bacterial nature, guided by the epidemiological considerations detailed above, and encouraged by the recent discoveries in the etiology of malaria, the American observers thought that possibly, as in malaria, the mosquito was an essential factor in the life cycle of the yellow-fever germ, as Finlay had conjectured many years before. After some preliminary experiments, which unfortunately proved fatal to Dr. Lazear, one of the original members of this courageous band of observers, carefully planned systematic attempts were made to convey yellow fever by means of the bite of the common West Indian mosquito, Stegomyia calopus (S. fasciata). Twelve non-immunes, who had had no opportunity of contracting the disease from other sources, were bitten by mosquitoes previously fed on yellow-fever patients. Of the men so bitten, ten (83.3 per cent.) developed the disease within the normal incubation limits— three to five days. Subsequently Guiteras and others, on repeating this experiment, have obtained similar results.
The germ not transferable by recently injected mosquitoes.— As might have been partly expected from the blood inoculation experiments already described, it was found that it was only mosquitoes that had fed during the first three days of the fever that were infective. It was further demonstrated that the germ must undergo in the mosquito some necessary developmental process, for it was not until twelve days had elapsed after feeding on yellow-fever blood that the experimental insects could convey infection. Repeated trials made with mosquitoes two to ten days after they had so fed invariably gave negative results; whereas the same insects rarely failed to infect when set to bite non-immunes at any time subsequent to the twelfth day after their yellow-fever blood meal. It was also proved that they retained their infective power for at least fifty-seven days.
These experiments fully explain— (1) The impunity with which a yellow -fever patient can be visited by a non-immune if outside the endemic area; the mosquitoes in the vicinity are not infective. (2) The danger of visiting the endemic area, especially at night; the mosquitoes there are infective and active. (3) The discrepancy between the incubation period, three to five days, of the disease, and the incubation period, fourteen days and over, of an epidemic; the necessary evolution of the germ in the mosquitoes infected by the original introducing patient demanding the space of time indicated by the difference between these two periods. (4) The clinging of yellow-fever infection to ships, buildings, and localities; the persistence of the germ in infected mosquitoes (Stegomyia calopus) which are known to be capable of surviving for five months and probably longer, after feeding on blood. (5) The high atmospheric temperature required for the epidemic extension of yellow fever; such temperature favours the activities and propagation of the mosquito, and is probably also necessary for the evolution of the germ in the mosquito.
Since the announcement of these discoveries many independent observers and several commissions have studied yellow fever in its relation to the mosquito, but, beyond confirming the results of the original American observers and adding some facts in the bionomics of S. fasciata, there has been no great addition to our knowledge of the subject. The germ itself is still unrevealed.
Marchoux and Simond have given us several new facts about the yellow-fever germ. They have shown that, although it is arrested by the Chamberland bougie B, it can pass bougie F ; that it will not infect if simply laid on a raw (blistered) surface; to secure infection it must be injected subcutaneously; that virulent blood-serum loses its virulence in forty- eight hours if exposed to the air at 24° to 30° C., but if protected by oil or vaseline will retain it for five days.
As regards S. calopus, the same observers note that to lay eggs she must first have a feed of blood, and that her eggs are deposited about three days after she has so fed. Before the first egg-laying, S.calopus is both diurnal and nocturnal in her feeding habits, biting at any time; subsequently she is strictly nocturnal in this respect. Therefore a stegomyia that bites during the day does not convey yellow fever. She is too young; any parasite she may harbour is immature. In this way is to be explained the impunity with which a yellow-fever centre may be visited during the day, although the visitor may be bitten by stegomyia. Europeans who live at Petropolis, a suburb of Rio de Janeiro, and are in the habit of visiting and transacting their business in the low-lying yellow-fever-haunted districts of the city, never contract the disease unless they are so imprudent as to pass the night in the latter. Marchoux and Simond further state that an infected stegomyia can communicate the yellow-fever germ to her eggs and so to the second generation of mosquitoes, and that the latter become infective to man fourteen days after the hatching.
The parallelism between the etiology of yellow fever and that of malaria is very complete, and encourages ' the conjecture that the germ, like that of malaria, is of a protozoal nature; that as a result of a sexual process it undergoes growth and development in the mosquito; and that the sporozoites resulting from this process are emitted in the salivary secretion of the infected mosquito when, at any time subsequent to the completion of the developmental process, she proceeds to feed on blood. Although the germ of yellow fever as it occurs in the blood may be ultramicroscopic, the analogy of the malaria parasite favours the idea that in the insect it may grow to a visible size, and that although search in the blood for the cause of this grave disease hitherto has proved unsuccessful, it may yet be demonstrated in the tissues of the mosquito. Further, as several species of mosquito of the sub-family Anophelinœ have been shown to foster the malaria parasite, it is not improbable that several species of the genus Stegomyia may turn out to be effective intermediaries for the germ of yellow fever. *[1]
Symptoms.— There is the same variety in the initial symptoms of yellow fever as in other specific fevers. There may be sudden rigor supervening in the midst of apparent health; there may be only slight chills; or there may be a period of premonitory malaise leading up to the more pronounced symptoms. When fairly started, the procession of events is rapid.
Roughly speaking, and provided there are no complications, an attack of yellow fever is divisible into three stages 1, the initial fever; 2, "the period of calm," as it is called; and 3, in severe cases, the period of reaction.
The initial fever lasts usually from three to four days. The maximum temperature is generally attained within the first twenty-four hours, or by the second day, and, in a case of medium severity, may rise to about 103° or 104° F. During the three or four succeeding days the mercury slowly sinks to 98° or 99°, the daily fluctuations being seldom more than half to one degree. It occasionally happens that high temperature is maintained for two or three days, and also that the maximum is not attained till the third day; as a rule the thermometer behaves as described, the maximum being reached within a few hours of the onset of the disease.
With or soon after the initial chill or rigor, severe headache sets in, and is generally a prominent feature. For the most part the pain is concentrated about the forehead, in the circumorbital region and in the eyeballs themselves. In many cases it is associated with intolerance of light.
Loin pain is another very distressing symptom; it may amount to positive agony. The legs, too, ache excessively particularly the calves, knees, and ankles; they feel as if broken. Epigastric pain is generally a prominent symptom.
The face is flushed and swollen; the eyes are shining, injected, and ferrety; the skin is dry.
What with pain and febrile distress, the patient rapidly passes into a very miserable condition. He is restless and continually tossing about.
At first the pulse ranges from 100 to 120, and is full and strong; but as the disease progresses the pulse loses its sthenic character, gradually falling in force and frequency until, at the " period of calm," it becomes remarkably slow and compressible, beating perhaps only 30 or 40 times per minute.
At the outset the tongue is not very dirty, but it soon acquires a white coating on the dorsum, the edges remaining clean. It is not so swollen and flabby as in malarial fever; on the contrary, it is rather small and pointed throughout the disease. This is regarded as an important diagnostic mark; taken along with the progressive diminution in the strength and frequency of the pulse, and the peculiar behaviour of the temperature, it is nearly conclusive as to the disease being yellow fever. Later, the tongue dries, and, at the same time, thirst becomes intolerable. The palate is congested and swollen; the gums may also swell and bleed.
The congested appearance of the face at the onset of the disease tends to subside; so that by the time the asthenic stage is reached the features may have become shrunken and small, the eyes sunken, and the eyelids discoloured by ecchymoses.
In some cases the skin is hot and dry throughout; in others it may be bedewed with perspiration from time to time; or the sweating may be constant, especially so if collapse sets in.
By the third day the scleræ assume a yellowish tinge, and very often the skin acquires the yellow colour from which the disease derives its name. It must not be understood, however, that every case presents this colour of skin; in some it is entirely absent, but if carefully looked for there is always some yellowness of the sclerae to be discovered. The yellow tinging of the skin generally shows about the end of the first stage, deepening in intensity as the case advances, and remaining apparent for a considerable time after convalescence has become established. It ranges in depth from a light saffron tint to a deep mahogany brown. In fatal cases it is always present; not necessarily during life, but invariably after death. The skin in bad cases is said to emit a peculiar odour like gun washings, or, as Jackson puts it, like the smell of a fish market.
Petechia], erythematous, papular, and other eruptions may show themselves in different cases; but in yellow fever there is no characteristic eruption, unless it be an erythematous congestion of scrotum or vulva, which occurs in a proportion of cases and is said to be diagnostic.
An important feature, from the diagnostic as well as from the prognostic point of view, is the appearance, in some cases almost from the outset of the disease, of albumin in the urine, together with a tendency to suppression. In mild cases these features may be little marked; but in severe cases, particularly during the stage of depression, the urine may fall to a few ounces, and be loaded with albumin to the extent of one-half or even two-thirds. The more pronounced these symptoms, the graver is the prognosis. Urea (even during the incubation period) and uric acid are very much diminished, the former in severe cases falling to 1.5 grm. to the litre. The urine is almost invariably acid, depositing granular casts, and giving spectroscopic evidence of hæmoglobin. Bile pigments show themselves towards the end of the disease; their appearance is regarded as a favourable omen. Hæmorrhage from kidneys or urinary tract is not uncommon.
Delirium may occur, but is not an invariable feature. Usually, after the initial stage of restlessness and acute suffering, the patient becomes torpid, and perhaps taciturn. In bad cases, coma, subsultus, etc., may gradually supervene, the temperature rising as death approaches and even after death.
At the outset the bowels are confined. In the second stage diarrhœa, perhaps of black material resembling the vomit, may supervene; or there may be actual hæmorrhage of bright-red blood from the bowel.
The well-known black vomit— always a grave symptom, but fortunately not by any means an invariable one— forms one of the most striking features of this disease. In the earlier stages of the fever vomiting of bilious matters is a common occurrence. This may subside, or, after a time, give place to a coffee-ground vomit which seems to gush up without straining or effort on the patient's part, and which gradually deepens in colour until it becomes uniformly black. On microscopical examination the vomited material is found to consist of broken-down blood corpuscles and altered hæmoglobin suspended in a yellowish mucoid fluid. This material is, doubtless, in the main derived from blood transuded through the walls of the capillaries of the mucous membrane of the stomach. It is intensely acid. Though the black vomit may not always be seen in fatal cases during life, it is invariably found in the stomach on post-mortem examination.
Sometimes pure blood is thrown up from the stomach; similar passive hæmorrhages may take place from almost any part of the body from eyes, ears, nose, mouth, bladder, uterus, and so on.
Death may occur during the early acute stage, being preceded by a rapid rise of temperature.
In mild cases the "period of calm," which sets in after the subsidence of the initial fever, may last for several days before convalescence is established. In such, recovery once begun is usually very rapid; in a week from the beginning of the disease the patient may be about again. In severe cases, however, the period of calm is followed by a third stage, the stage of reaction, in which the temperature again rises, though not to so high a point as in the initial fever, and a sort of remitting fever of an adynamic type keeps on for several days or weeks. This secondary fever is more prolonged if there is any complication, such as abscess, boils, parotitis, buboes, hepatitis, and so forth. The icterus is now very pronounced; black vomit may recur, or appear for the first time; perhaps a profuse diarrhræ ends in collapse; or the urine may be suppressed, stupor, coma, and other nervous symptoms ensuing, and very often ending in death. In other instances the secondary fever terminates in a crisis of sweating and a prolonged convalescence.
Relapse may occur at any time up to two or three weeks after the subsidence of the initial fever. It is specially prone to occur if the patient has been guilty of any dietetic imprudence during the period of calm —a period at which the appetite may return to some extent. Relapses are very dangerous.
'Prognosis and mortality.— Prolonged initial rigors, algidity, convulsions, suppression of urine, coma, hæmorrhages, are all unfavourable symptoms. The prognosis is good if the temperature during the initial fever does not exceed 103° to 105° F. It is better for women (although, if pregnant, abortion is almost invariable) and children than for men; better for old residents than for new-comers; worst of all for the intemperate. According to a table given by Sternberg, of 269 carefully observed cases there were no deaths in 44 cases in which the temperature did not rise over 103°; per contra, in 22 cases in which the thermometer rose over 106° there were no recoveries. Of 36 in which the temperature rose to between 105° and 106°, 22 died; of 80 with maximum temperatures between 104° and 105°, 24 died; and of 87 in which it ranged between 103° and 104°, only 6 died. The mean mortality in the whole 269 cases was 27.7 per cent. Although in some epidemics it has risen as high as 50 or even 80 per cent, of those attacked, the foregoing may be taken as a fairly representative mortality in yellow fever among the unacclimatized— something between 25 and 30 per cent. Among the permanent inhabitants of the endemic districts the case-mortality is very much lower— 7 to 10 per cent. During epidemics abortive and ambulatory cases occur; in these, icterus and other characteristic symptoms are often absent. Such cases may be hard to diagnose from febricula or mild malarial attacks. In them the mortality is nil. Some epidemics are particularly mild; in others the majority die. In the same epidemic the cases may vary in severity from time to time. In children the mortality is insignificant.
Pathological anatomy.— Depending probably on hæmoglobin diffused in the liquor sanguinis and tissues, and not on biliary pigment, the yellow colour of the skin is most marked in the dependent parts of the cadaver, especially in those parts which are subjected to pressure. Petechise are common in the skin and serous membrane; more considerable extravasations of blood may be found in the muscles. The brain and meninges are hyperæmic, and may be studded with minute hæmorrhagic effusions; like the other tissues of the body, they are stained a lighter or deeper yellow. The blood in the vessels of the general circulation is not firmly coagulated. The blood corpuscles appear to be normal, although there can be little doubt that there is in this disease a liberation of hæmoglobin, arising, possibly, from destruction of a proportion of the corpuscles. An important fact, as explaining the liability to passive hæmorrhages, is the existence of a generalized fatty degeneration of the capillaries and smaller blood-vessels. The stomach, as stated, always contains more or less black material, sometimes fluid blood, such as may have been vomited during life. The folds of the gastric mucosa are swollen ; here and there are arborescent patches of congestion, and ecchymoses. Observers are not agreed as to the nature of this congestion— whether it is passive or inflammatory. Sternberg says that in the increase of leucocytes in the sub-mucosa there is evidence of a slight inflammatory action. The small intestine may contain a dark, acid material similar to that in the stomach, and doubtless coming from the same source. Like that of the stomach, the mucous membrane of the intestine shows patchy arborescent injection.
As compared with other fevers, in yellow fever the liver is characteristically affected. As a rule, if death has occurred at the later stages, this organ is somewhat exsanguine, friable, and presents a yellowish colour from profound fatty changes in the cells. Occasionally, though rarely, it may be hyperæmic and dark. Throughout the gland the cells particularly those about the periphery of the lobules— on microscopical examination are found to contain globules and grains of fat. The nuclei in some instances, as well as the protoplasm of the cells, show fatty changes; the latter may be completely disintegrated. In the great majority of cases this fatty degeneration is well marked. It is not confined to the liver; every organ of the body is more or less affected in the same way.
The spleen is not characteristically affected, but the kidneys show signs of parenchymatous nephritis. Hæmorrhagic foci under the capsule and in the cortex are common. The renal epithelium shows cloudy swelling passing on to fatty degeneration and desquamation. The tubules, here and there, are filled with infarcts, either of an albuminoid material or of débris of desquamated epithelium, corresponding with the numerous casts which can be discovered in the albuminous urine. Diagnosis.— The diagnosis of yellow fever is treated of in one of the chapters on malaria and in that on black water fever (see pp. 114, 288). Practically, the only two diseases with which severe yellow fever is likely to be confounded are bilious remittent and hæmoglobinuric fever. The difficulties of diagnosis are often very great; particularly so in the earlier cases of an epidemic. When several deaths, preceded by fever and black vomit, have occurred within a limited area and in quick succession, a suspicion of yellow fever becomes a certainty. There is no clinical feature, so far as is known, which would distinguish a mild attack of yellow fever from an ordinary febricula, nor any pathognomonie clinical sign that would absolutely distinguish a malarial remittent from yellow fever. Probabilities must be weighed in diagnosis when it is based on clinical grounds alone. The only reliable guides are the discovery of the malaria parasite and the characteristic pigment and leucocytic variation in malarial fever, and the determination of their absence in yellow fever ; and, when cases come to the postmortem table, the presence of pigment in the viscera in the former, and of extensive fatty degeneration of the liver cells in the latter.
Treatment.— Formerly a much more active treatment than that in vogue at the present day was the fashion for yellow fever. It is now recognized that, as with most specific fevers, the treatment is more a matter of nursing than of drugs.
Experience has shown that a smart purgative at the very onset of the disease is beneficial. With many castor oil is the favourite drug, but to be of service it has to be given in very large doses 2 to 4 oz. Others use calomel; or calomel combined with quinine— 20 gr. of each. Others, again, prefer a saline. The purgative, whichever be selected, must not be repeated, nor, for that matter, given at all if the patient is not seen until after the second day of the disease. Hot mustard pediluvia, frequently repeated during the first twenty -four hours, the patient and bath being enveloped in a blanket, are much in favour. They are said to relieve the cerebral congestion and the intense headache. Very hot baths, with subsequent blanketing and sinapisms to the epigastrium, are also said to have a similarly favourable influence on the congestion of the stomach which is, undoubtedly, another constant feature of the disease. For high fever, antipyretic drugs, cold baths, iced injections, cold sponging, and the like may be carefully employed. In view of the asthenic nature of the disease, the less depressing measures should be preferred.
Vomiting may be treated with sinapisms and ice pills, or with small doses of cocaine. Morphia is dangerous, and must be avoided. For black vomit, frequently repeated doses of perchloride of iron, ergotine injections, acetate of lead, and other styptics have been recommended. For restlessness, phenacetin or antipyrin is used. When the skin is dry, the urine scanty, and the loins ache excessively, Sternberg recommends pilocarpine.
After the fourth or fifth day the flagging circulation demands stimulants of some sort. Iced champagne, hock, or teaspoonful doses of brandy given every half-hour may tide the patient over the period of collapse. Great care, however, should be exercised in the use of these things; if they seem to increase the vomiting and the irritability of the stomach, they must be stopped at once.
The feeding is an important matter. So long as there is fever the patient has no appetite; during this time— that is, for the first two or three days— he is better without food. When the fever subsides appetite may return, and a craving for nourishment become more or less urgent; the greatest care, however, must be exercised about gratifying this untimely appetite. Only the blandest foods, and these only in very small quantities, should be allowed —such as spoonfuls of iced milk or chicken tea. Gradually the quantities may be increased; but, even when convalescence is established, solid food must be partaken of very sparingly, and it must be of the simplest and most digestible description. Indiscretion in eating is a fruitful cause of relapse in yellow fever; and it must be borne in mind that in this disease relapse is exceedingly dangerous. Nutrition may be aided by nutrient enemata.
The Sternberg treatment.— Sternberg has introduced a system of treatment by alkalis which promises well. It is directed principally to counter-acting the hyperacidity of the gastric and intestinal contents— always a marked feature in yellow fever. His prescription is 150 gr. of sodium bicarbonate and ⅓ gr. of mercury perchloride in a quart of water; of this 1½ oz. is given every hour. This, he claims, not only neutralizes the acidity of the intestinal contents but increases the flow of urine, the perchloride of mercury tending to check fermentation changes in the alimentary canal. Of 301 whites treated in this way only 7.3 per cent, died, and of 72 blacks all recovered. Other encouraging figures have been ad- duced as to the efficacy of this line of treatment, which is certainly deserving of further and more extended trial.
Prophylaxis.— It is the duty of sanitary authorities in tropical countries, so far as possible, to free of mosquitoes the areas over which they have charge. If this were effectually done everywhere there would be no malaria, no filariasis, and no yellow fever. Although complete extermination of mosquitoes is not to be expected, relative extermination of mosquitoes is worth attempting, and certainly much can be attained in this direction by the vigorous use of the now well-known measures. In Havana, by such means, in a very few months the number of mosquitoes was reduced 90 per cent., with, doubtless, a corresponding gain to the community in the diminution of mosquito-conveyed disease. The same has happened in Panama, Rio, and elsewhere.
During epidemic visitations or during exacerbations of endemic yellow fever, non-immunes should, if possible, immediately quit the implicated locality. Above all, the slums and low-lying districts of the town should be shunned. These places should not even be visited; or, if visits have to be made to them, they should be as brief as possible, and not made after sundown. The susceptible should not sleep in the lower storeys of houses, and should pay great attention to general health, carefully avoiding all causes of physiological depression or disturbance. Sailors must not be allowed on shore.
In every country subject to visitations of this disease the sanitary condition of the towns should be most carefully attended to, especially as they refer to the stegomyia mosquito. All water- tanks and cisterns must be effectually screened by fine-meshed metallic gauze; all puddles and stagnant water abolished; all cases of any kind of fever, no matter how mild they may be or what their nature, must be reported at once to the central sanitary authorities, who should have full powers promptly to screen or otherwise deal with them and the houses in which they are.
Any delay in recognizing the earliest cases of a threatened epidemic, as shown by experience in New Orleans, is most dangerous, leading, as it may, to the rapid multiplication of infected centres.
Ships should not be allowed to clear from infected ports, nor to enter non-infected ports during the warm season, without adequate inspection. If, on entering port, yellow fever is found on board, the cases should be isolated in a quarantine hospital where there are no stegomyia mosquitoes, the ship thoroughly cleared of mosquitoes, and the passengers and crew prevented for at least five, better thirteen, days from communicating with the shore, or until every risk of conveying infection has passed away.
In the event of the disease appearing in a locality which is not habitually a yellow-fever centre, and of which the population is small, an economical plan of dealing with the threatened danger is for the authorities promptly to remove the entire population of the neighbourhood, with the exception of the insusceptible and those in attendance on the sick, and to place the deported population, before dispersion, in a thirteen days' quarantine camp. Mean-while the infected area must be rigidly isolated and its mosquitoes destroyed. In this way the spread of the disease will be prevented.
In the event of yellow fever breaking out in the crew of a man-of-war, the cases, if possible, should be sent ashore, and the ship hurried north or south into cold weather, any mosquitoes which may have found their way on board being at once destroyed.
In the case of the appearance of yellow fever in a large town, the method which was so successfully adopted by Surgeon-General Gorgas, U.S.A., must be adopted. Funds and authority must be obtained at once. An efficient and adequate sanitary staff must be promptly organized and instructed in their duties. Cases of every kind of fever as well as cases of yellow fever should be immediately reported, and the patients promptly protected from mosquito bite by wire screens. At the same time the systematic destruction of mosquitoes in their breeding-places and in the patients' and neighbouring houses must be rigidly enforced. The infected houses should be carefully sealed up by pasting paper over all the doors, windows, ventilators, chimneys, and cracks, and the fumes of pyrethrum or of burning sulphur— 2 Ib. per 1,000 cubic feet of space— or other insecticide employed to stupefy the insects, which should afterwards be swept up and burned. In this way, in 1901, yellow fever was stamped out in ninety days in Havana, a city where for a period of 140 years it had held uninterrupted sway. In this way, in 1905, New Orleans was freed from the disease in a much shorter period than in any previous epidemic; and in this way Gorgas has made the line of the Panama Canal as healthy as New York. Similar results from similar measures are being obtained in the larger Brazilian ports.
Guiteras has shown, in a practical manner, that yellow-fever patients may be admitted to the wards of a general hospital or be nursed in private houses with impunity, provided they are protected by effective mosquito netting from mosquito bite during the first three or four days of their illness.
Portability of the virus in fomites and merchandise.— Until recently it was universally believed that the virus might remain for a considerable time potentially infective in fomites, clothes, merchandise, etc., and in wooden structures (ships). Thus, Strain describes an epidemic in São Paulo in which he believed the initial cases acquired the infection from unpacking a box of clothes which had lain at Santos for some time and had been damaged there by damp and sea- water. The epidemic of 1893 in the same city he traced to certain cases of machinery which had lain for some months at Santos. On opening the cases the packing straw was found to be damp. Four of the people in the house where the cases were opened got yellow fever within a few days.
Many similar instances have been adduced as conclusive evidence of the portability of the virus of yellow fever in fomites. But the very thorough and carefully conducted experiments carried out in Cuba by Drs. Reed, Carroll, and Agramonte go far to prove that fomites have nothing whatever to do with the conduction of the disease. A small, illventilated, badly lighted wooden hut was erected near Havana during the prevalence of epidemic yellow fever. The fresh and stale fomites of yellow - fever patients, in the shape of soiled bedding, clothes, black vomit, etc., were strewn about or stowed away in great profusion in this close hut, and among them, lying on beds that had been occupied recently by yellow -fever patients, wearing these patients' soiled night -clothes and using their soiled blankets, seven non-immunes (that is, white men, recently arrived and never previously affected with yellow fever) slept during, in the aggregate, sixty-three nights— from November 20th, 1900, to January 31st, 1901— with absolute impunity.
Immunity of the native as affected by anti-stegomyia sanitation.— The immunity of the native of the endemic areas of yellow fever is usually attributed to a mild attack in childhood. If yellow fever has been exterminated from Havana and other endemic centres by anti-stegomyia and other measures, the children in these places can no longer be attacked by the disease. It follows that, in the course of one generation, the entire population will become non-immune. Doubtless, sooner or later the germ of yellow fever will be introduced again, and then, having a population entirely non-immune to spread in, unless promptly checked, a far more extensive epidemic than ever devastated these places in less scientific days will ensue. This can be confidently predicted if it be true that the present immunity of the native depends on an attack of ordinary yellow fever in childhood. I am inclined to think that this explanation does not cover the entire ground; for, if the disease be so mild in childhood as not to be recognizable, how was it that Gorgas stamped out yellow fever in Havana, and how is it that the disease is not in evidence there now? I would suggest that there are two strains of yellow -fever virus one of great virulence, one of little virulence. Specifically the same, they are mutually protective, much in the same way as with vaccinia and smallpox. The immunity of the native and the old resident I would attribute to epidemics or endemics of the mild strain of yellow fever, which, could it be recognized clinically, might be used as a vaccine against the more virulent disease.*[2]
Introduction of yellow fever into Asia.— There is another important matter in connection with this disease which, in the near future, ought to be made a subject for international consideration. I refer to the possibility of the spread of yellow fever +987to Asia, the Eastern Archipelago, Polynesia, and East Africa. It has spread in the past to Europe; this is a comparatively unimportant matter, as the climatic and hygienic conditions in that continent are not favourable to the stegomyia mosquito, and therefore to the extension of the disease. It is otherwise in this respect, it is to be feared, with Asia. Fortunately, yellow fever, so far as known, has never appeared in the crowded, filthy cities of the East ; but, should it ever be introduced there, the favourable climatic conditions, the surpassing filth everywhere, the presence of stegomyia mosquitoes, and the too frequent absence of efficient sanitary machinery will enable it to spread like wildfire in an entirely non-immune population. The probable reason of its non-introduction into Asia is that the trade route from the West Indies and Central America to China and India has hitherto not been a direct one, but has passed by a long circuit either to the north or to the south. When the American interoceanic canal is in full use there will be direct and rapid communication between the present yellow-fever centres and Asia. With this more direct and more rapid communication there will arise a corresponding risk of spreading yellow fever into a huge section of tropical humanity which has hitherto enjoyed exemption from one of the deadliest diseases afflicting mankind. An infected mosquito (and Stegomyia calopus, according to Giles, is a good traveller), either shipped by accident or brought on board by some thoughtless or malicious person, could easily be conveyed alive to the shores of Asia, and would suffice to set, so to speak, the whole of the tropical section of the Eastern hemisphere in a blaze. The history of the spread of disease by the rapid methods of modern travel is full of examples that should serve as a warning to our rulers and responsible sanitary authorities. Let us hope that
this important matter will receive the attention it demands, and that due care will be exercised that America does not reciprocate the introduction of cholera from Asia by a return gift of yellow fever. Genus Stegomyia
The members of this group of mosquitoes, belonging to the sub-family Culicinœ, present very distinctive characters. Their ova, instead of being cemented together to form rafts as in other Culicinœ, are deposited separately, each being surrounded by small air-chambers. Their larvæ are somewhat elongate, with rudimentary antennæ, and a short stout siphon; they maintain art almost vertical attitude. In the nymphæ the trumpets are expanded and broadly triangular in shape. The imago exhibits a distinctive scale structure and, at all events in early life, observes diurnal habits.
The Stegomyiœ are easily recognized by the broad, flat, imbricated scales which completely cover the head and abdomen and which are invariably present on the middle lobe and frequently also on the lateral lobes of the scutellum. These scales give to the insect a satin-like appearance which is quite characteristic. They are mostly small, black insects, with white, silvery, or yellow lines, bands, or spots on the thorax and legs. In India they are known as "tiger mosquitoes" on account of their striped appearance. They seem to have a decided preference for the littoral, and certain species (S. calopus, S. scutellaris) are frequently found on ships and are doubtless distributed by this means. At present the genus Stegomyiœ includes nineteen species, all of which are easily identifiable on account of their striking thoracic and other ornamentation. Of these the type species, S. calopus, is the most important on account of its wide distribution in all tropical and sub-tropical countries, and of its share in the propagation of yellow fever.
S. calopus (Plate VII.) can be recognized by the peculiar lyre-shaped ornamentation of its thorax, composed of two dull yellow parallel lines in the middle and a curved silvery line on each side.*[3] The proboscis is not banded; the abdomen is banded basally; the last hind tarsal joints are all white, and some of the other tarsal joints are marked by light bands basally. This widely distributed species is essentially a domestic form and bites with avidity. It breeds in small artificial collections of water, such as barrels, puddles, cisterns, and even in such small receptacles as sardine tins. The nature of the water appears to be a matter of indifference. The eggs resist a considerable degree of desiccation, and, as they may sink to the bottom of the water in which they lie, are readily pumped into the water-tanks of ships.
Although widely distributed, S. calopus does not occur abundantly in certain parts, such as the Malay States, China, and Africa, where its place is taken by closely allied species, such as S. scutellaris in the Malay States, China, etc., and S. africana, S. argenta punctata, and others in Africa. It is quite possible that, besides S. calopus, other species belonging to the genus may be able to transmit the yellow-fever germ. 
Stegomyia calopus (fasciata), ♀.
Plate VII.
- ↑ * In Africa, S. afrikana, S. argenta-punctata, S. sugens.
- ↑ * Thomas has communicated yellow fever to the chimpanzee; possibly to the guineapig. Doubtless there are other lower animals susceptible to the infection. A passage through one of these may deprive the germ of its virulent pathogenic properties. The omnipresent stegomyia would be an active vaccinator of the non - virulent strain, passing it from native to native, and so rendering them immune against the virulent form of the disease. At all events, until proof is adduced that something of this sort does not occur, the possibility that it does occur should not be ignored.
- ↑ * This ornamentation is constant, but the median thoracic stripes are absent in a variety called S.fasciata mosquito.