Yellow fever an acute viral disease characterized by sudden onset, prostration, moderately high fever, and a pulse rate slow in relation to temperature. Severe cases are often characterized by vomiting of altered blood, albuminuria (sometimes massive), and jaundice, and may progress to collapse and death. The disease is endemic in tropical rain forest regions of Africa and South America: in the past, summer epidemics occurred sporadically in the temperate zone even in New York and Philadelphia, and persistent endemic foci existed in the larger coastal cities of South America, Africa, and the Caribbean region. There are two epidemiologic types of the disease. When the virus is transmitted from man to man by the domestic mosquito, Aedes aegypti, it is called urban yellow fever. but when it occurs in a forest environment and is transmitted to man by some forest mosquito, usually in the absence of A aegypti, it ’is called sylvan tor jungle) yellow fever.
Etiology and Epidemiology.
Yellow fever is a group B arbovirus, according to Casal’s serologic classification of the arboviruses. Related viruses in group B include among others the causative agents of the dengues, Japanese B encephalitis, St. Louis encephalitis, and Russian spring-summer encephalitis. The virus is small, 38/x ± 5m/x and readily passes Berkefeld V and N and Seitz filters. Unadapted virus exhibits both viscerotropic and neurotropic characteristics. Viscerotropic is manifested by involvement of liver, kidneys, and heart, and neurotropism by infection of cells of the central nervous system. By successive brain- 4o-f crain passage in mice, the virus becomes adapted and manifests more neurotropism, losing its viscerotropic properties almost entirely. Prolonged passage of the virus in chick embryo tissue culture has produced an attenuated strain, 17D, widely used as a vaccine.
Man is universally susceptible to, the virus, and characteristic symptoms and lesions of yellow fever in man are reflections of its viscerotropic. Certain monkey species, including Macacus rhesus and Alouatta species, are very susceptible to infection and usually die, whereas other species, for example, Cebus species, may be readily infected but usually recover. Albino mice, especially of the Swiss strain, are highly susceptible to the neurotropic element of virus strains recovered from nature, provided they are inoculated intra- cerebrally.
In urban yellow fever, the A, aegypti mosquito transmits the virus by biting a human host during his initial three-day period of viremia and later biting a susceptible person. An extrinsic incubation period of nine to twelve days in the mosquito must elapse before the mosquito can transmit infection by bite.
In sylvan yellow fever, man acquires his infection through the bite of some mosquito other than A. aegypti. In south and Central America the virus has been isolated from wild-caught mosquitoes of the genus Haemagogus, Aedes leuco- celaena, and Sabethes chloropterus. These are by far the most important vectors. In Africa virus has been recovered from wild-caught Aedes simpsoni and A. africanus. Haemagogus and A. africanus inhabit chiefly the forest canopy, which is also the habitat of monkeys, the most frequently infected wild hosts. Aedes simpsoni is found in areas of mixed cultivation and low secondary forest, often near human habitation, and bridges the gap between the deep forest and the primitive settlements and between forest monkeys (raiding crops near the settlements) and man.
A cycle for virus maintenance in nature more basic than the mosquito-monkey-mosquito cycle has been diligently searched for but not found.Since 1934 no large epidemics of urban yellow fever have been reported from the Western Hemisphere, and the few small A. aegypti-transmitted epidemics that have occurred, such as that in Trinidad in 1954, have been secondary to sylvan yellow fever. The announcement of urban yellow fever, A. aegypti-transmitted, in a seaport or airport brings strict international quarantine regulations into effect.
The 1948-1957 epidemic of sylvan yellow fever in Panama and Central America has burned itself out after decimating the monkey populations. As the monkey populations are reestablishing themselves, however, repeated epidemic sweeps are a certainty. In Africa, in areas contiguous to the rain forest areas where sylvan yellow fever is endemic, there are still frequent epidemics of urban yellow fever. A large epidemic occurred in the Nuba mountains of Sudan in 1940, and others in Nigeria in 1946 and 1951-1952. A massive outbreak in southwestern Ethiopia in 1961-1962 caused an estimated 35,000 deaths.
Aedes simpsoni was demonstrated to have been an important vector in this epidemic. More recent epidemics have been reported from Portuguese Guinea in 1964-1965, from Senegal in 1965 and from Nigeria in 1969.There is no evidence that yellow fever has ever been present in the Orient.Using refined serologic techniques, it is possible to distinguish Old World strains of yellow fever virus from New World strains. The significance of this with regard to geographic epidemiology and relating to the original home of yellow fever is not settled.
Pathology.
Yellow fever produces characteristic lesions in the liver of man. There are necrosis and necrobiosis of the parenchymal cells, most evident in the mid zones of the lobules, with normal or much less involved cells around the central and portal veins. The necrosis is scattered and irregular rather than massive and uniform. Scattered among the necrotic cells are Councilman bodies, parenchymal cells that have undergone eosinophilic hyaline necrosis. There are also fatty changes in the parenchymal cells. The liver lobules are not collapsed. Pathologic changes in the kidneys are seen mainly in the tubules, with extensive damage to the epithelium and with lumina containing debris, casts, and basophilic concretions.
Clinical Manifestations of Yellow Fever And Yellow Fever Symptoms.
Most attacks of yellow fever are mild and show few if any of the classic symptoms. The only symptoms may be fever and headache, both of short duration. The epidemiologic implications of this disease make diagnosis of great importance, and it is essential to maintain a high index of suspicion with regard to undiagnosed fevers ‘vernacular terms: “P.U.O.,” “F.U.O.,” flu,” etc.; in regions where yellow fever is known to be, or can be suspected of being, endemic.
The incubation period is from three to six days. The onset is sudden, often with a chill, and without prodromal symptoms. The first stage of the disease, which lasts about ‘three days, is the period of infection. The symptoms are feverish feeling, severe headache, backache, pain in the legs, and prostration. The face is flushed, and the eyes are injected; there is photophobia. The tongue is bright red at the tip and edges. There is no jaundice at the onset of illness. The temperature rises abruptly to about 104° F., sometimes higher. The pulse rate may rise to 90 or 100 initially, only to become increasingly slow in relation to the temperature (Faget’s sign).
The pulse is strong and full during this stage. Nausea and vomiting are the rule, as are epigastric distress and tenderness. Constipation is to be expected. A progressive leukopenia, sometimes pronounced, has frequently been observed early in the disease. The sudden development of intense albuminuria about the third or fourth day is characteristic. After a short remission, the period of intoxication begins about the fourth day. The remission in fever is often indefinite or absent, and it may be accompanied by a deceptive temporary improvement. In this period, lassitude and depression may replace restlessness and agitation.
Headache may diminish, and jaundice gradually develops. Although jaundice is always present in severe cases, it is usually not so intense as the name of the disease would indicate. Various hemorrhagic manifestations are evident. The gums are swollen and bleed easily, either spontaneously or when pressed; the nose may bleed. There may be petechiae in the skin. Hemorrhages from the stomach, intestine, or uterus, or subcutaneously, may be massive. The pulse rate falls progressively and may go below 50 per minute.
Even in otherwise mild cases there may be dilatation of the heart and low blood pressure as evidence of myocardial damage. Vomiting may be frequent and distressing, and the vomitus in this stage usually contains altered blood, whence the name “el vomito negro” often applied to the disease in Latin America. The amount of albumin in the urine rises, often to 3 to 5 grams per liter, sometimes much higher. Fatal cases often exhibit hiccup, copious vomiting of altered blood, tarry stools, and anuria. Coma may last two or three days, or death may be immediately preceded by a short period of wild delirium. Death occurs most frequently from the sixth to the ninth day.
When there is recovery from a severe case, the temperature is likely to reach normal by the seventh or eighth day. Convalescence begins then and progresses rapidly to complete recovery with rapid disappearance of the albuminuria. Relapses do not occur, and there are no sequelae. Complications are rare. A lifelong immunity follows the attack, whether it be mild or severe.A feature of yellow fever is the great variation in the degree to which different organs are affected. With much renal involvement there may be no cardiac symptoms, and vice versa. In mild and moderate cases there is little or no albuminuria, jaundice, or hemorrhage.
Diagnosis.
In a severe illness with “black vomit,” intense albuminuria, jaundice, and melena, as a group or in combinations, yellow fever must be suspected. Diseases that must be differentiated from severe yellow fever include infectious and serum hepatitis, “acute yellow atrophy” of the liver, carbon tetrachloride poisoning, other jaundices, malaria, and typhoid. In mild cases, which have been confused with dengue and influenza, clinical diagnosis is notoriously inaccurate. The necessary laboratory procedures are highly specialized.
The isolation of virus in mice, rhesus monkeys, or certain tissue cultures from serum of the acutely ill patient or from serum or liver of a deceased patient affords convincing diagnosis. Specialized, procedures are needed for the identification of the isolate. Serologic tests on paired acute-phase and convalescent serums, using techniques of complement-fixation, hemagglutination-inhibition, and virus neutralization, can also give positive diagnosis. Although the tests must be done in a specialized laboratory serum specimens can be collected and submitted to such laboratory.
For postmortem diagnosis, specimens of liver and other tissues should be preserved in 10 per cent formalin for histologic examination. Virus recovery can be attempted from such tissues if small pieces are placed in 50 per cent glycerol- saline and shipped, under refrigeration if possible, to a laboratory.
Prognosis.
Early in the disease the prognosis should be guarded, because sudden changes for the worse may occur. If early symptoms are mild, rapid recovery is probable. Some patients with severe disease will recover, but symptoms of hiccups, copious black vomit, melena, and anuria imply a very grave prognosis.
The over-all average case fatality rate is less than 10 per cent, and rates of less than 5 per cent have been observed in epidemics involving completely susceptible populations. Rates as high as 85 per cent have been observed, but they are most exceptional. Even the often cited 50 per cent is misleading, since in earlier, and also in present day epidemics, large numbers of mild cases may go undiagnosed.
Yellow Fever Treatment,Being A Doctor You Must Know.
There is no specific treatment. A patient should be moved as little as possible and should be kept quiet in bed. Heroic efforts to get a patient from some remote area to a district hospital should be discouraged. The severe headache and body aches may require relief with an analgesic. The heart should be watched carefully throughout the illness and into early convalescence.
Water should be given in adequate amounts, parenterally if necessary. Easily assimilated food should be given to the extent that the patient will tolerate. Milk in moderate quantities can be recommended. When vomiting has ceased and the temperature is down, full diet may be given. Full activity should be resumed only gradually.
Prevention.
If a case of yellow fever is treated in a place in which vector mosquitoes exist, the patient must be kept under a bed net or in a mosquito-proof room during the first four days of illness.Vaccination is essential for persons who intend to visit yellow fever endemic areas and for the people resident in such areas. Yellow fever is notorious for existence in endemic areas with no overt signs of its presence, and despite negative reports of the most recent weekly international epidemiological bulletins relative to a given area, vaccination for persons going to an endemic area must be stressed. Two strains of living virus have been used extensively for human vaccination. The 17D vaccine is prepared in chick embryos and is given by subcutaneous inoculation.
At the Pasteur Institute of Dakar, the technique of vaccination by scarification of the skin was developed, using the neurotropic French strain suspended in gum arabic solution. With either strain, an effective immunity to yellow fever is regularly produced, provided that viable vaccine is used. Severe reactions to the Dakar type of vaccine are more frequent than are reactions to 17D. Vaccination ordinarily gives protection in a week, and the consequent immunity has been shown to last at least ten years. An urban epidemic can be stopped by mass vaccination of the population combined with vigorous anti-aegypti measures.
