YELLOW FEVER (Latin. febris flava; synonym: febris biliosa, typhus icteroides) — the natural and focal acute two-phase viral disease transmitted by mosquitoes at a cut the heavy hemorrhagic syndrome, damage of a liver and other bodies and systems often develop. Distinguish two main epidemiol, type Zh. l. depending on properties of a carrier: local (dzhunglevy, or rural) and epidemic (antroponozny, or city). l. belongs to to quarantine diseases (see) to which extend international medical - a dignity. rules (1969).
First reliable epidemics. l. were in 1647 and 1648 on the islands of Barbados, Trinidad and on the coast of the Caribbean Sea (Central America).
During colonization of the Western Africa, Central and South America troops of conquerors, participants of numerous expeditions sustained big losses from epidemics. l. E.g., 7 — 8 thousand survived Leklerk's expedition to San Domingo from 30 thousand people.
In 1898 — 1900 the Spanish army in Cuba lost from. l. 30 thousand persons.
With development of intensive commercial relations. l. more than once brought to Europe and North America. So, in Spain at the beginning of 19 century from 270 thousand diseased from. l. 79 thousand died. Epidemics were also registered in France, Italy, Portugal. In the USA from 1793 to 1900 had. l. not less than 500 thousand persons.
In the 20th century. l. generally struck the countries of tropical zones of Africa and South America.
Judgments of the virus nature of a disease and of a carrier of a virus were stated for the first time by the Cuban doctor K. Finlya in 1881. These judgments after (1901) were validated also by the commission on. l. led by doctor W. Reed.
Long-term protivoepid, actions led to the fact that by 40th 20 century of flash epidemic. l. in the countries of the American continent practically stopped. Local. l. still is registered in the countries of South America, in Mexico, and also in the countries of tropical and subtropical Africa. Centers of local. l. remained in Brazil, Colombia and Venezuela. In South America from 1948 to 1958 1606 diseases, in 1969 — 48, in 1970 — 86 were observed. The centers are more active. l. in Africa (Nigeria, Zaire, Zambia, Uganda, Kenya, Somalia, Sudan, Congo, Togo, Ghana). So, in 1940 in Sudan there was epidemic, in time a cut the St. 15 thousand had, 1,5 thousand persons died. In the 60th. l. in Africa arose also out of the local centers: in Ethiopia in 1960 — 1962 more than 200 thousand people from whom died apprx. 30 thousand
the Activator Zh were ill. l. Flavivirus febricis is opened in 1901 by Read and Carroll (W. Reed, J. Carroll), treats to an arbovirus of antigenic group B, the Togaviridae family; its sizes apprx. 40 nanometers. The virus is filtered through plates Millipor with a diameter of time of 100 nanometers, has spherical shape, the external cover contains lipids and lipoproteids; in virion — one RNA thread covered with proteins. Virus Zh. l. it is sensitive to processing by ether, dezoksikholaty sodium, it is quickly inactivated by usual desinfectants and at a temperature St. 60 °. A virus it is long remains in the frozen fortune and in 50% glycerin (over three months); maintains lyophilizing).
The virus can be allocated from blood (plasma) of the patient in the first 3 days of a disease, and also from a liver, a spleen, blood — in section cases. l., infection of newborn white mice or monkeys in whom it causes an acute disease. Cultures of kidneys of monkeys or a pig, and also a cell of fabric of a chicken embryo well support reproduction of a virus Zh. l. In cultures of fabric the virus causes destruction of cells, forms plaques and Hemagglutinins. Immunol, identification of virus strains. l. it is carried out by specific immune serums in neutralization tests of a virus, braking of passive hemagglutination and fixation of the complement. As sources of antigens for serol, reactions use a brain of the infected mice or monkeys, and for production of a vaccine — fabrics of a chicken embryo or a brain of the mice infected with virus strains. l.
The virus breeds in an organism of a mosquito after it nasostsya viruliferous blood of the sick person or an animal.
See also Arbovirus .
Sources of a virus at local. l. monkeys, perhaps, rodents, hedgehogs, etc. serve. Carriers of activators in America — forest mosquitoes of the sort Haemagogus and Aedes leucocelaenus, in the countries of tropical Africa — a mosquito of Aedes africanus, a midday mosquito of Aedes simpsoni and, perhaps, other types of Aedes. Large epidemics. l. Ethiopia was connected with Aedes simpsoni.
Local. l. it is characterized by low incidence and is registered constantly, from year to year; the men working in the woods get sick in South America preferential (lesorazrabotka, hunting etc.). In the equatorial Africa this type Zh. l. also the hl meets. obr. in the form of sporadic diseases. L. V. Gromashevsky explains small prevalence local. l. in Africa high latent immunization of local population under natural conditions. Therefore, in particular, diseases meet among the alien population more often.
Penetration of a virus Zh. l. from the local centers to settlements where the mosquito of Aedes aegypti meets, can lead to formation of other type of the center — epidemic. In this case the disease extends in the cities, large settlements, and under favorable conditions and beyond their limits.
The person is a source of infections in these centers. A carrier — a mosquito of Aedes aegypti; it is widespread between 42 °C. highway and 40 ° SL, outside these latitudes meets seldom. The mosquito of Aedes aegypti which got drunk blood of the patient Zh. l., becomes infectious in 9 — 12 days depending on air temperature and keeps a virus until the end of life. Transovarial transfer of a virus is not confirmed. This mosquito belongs to forms of the Old World; according to Teyler (M. of Theiler, 1951), it was brought in the Western hemisphere in old time. Practically Aedes aegypti became synanthropic, living in dwellings of the person or near them, laying eggs in water of artificial reservoirs. It defined antroponozny character. l., at Krom circulation of a virus is provided in a closed circuit of people — a mosquito — the person. With a sufficient number of a carrier, considerable number of people, susceptible to an infection, and favorable heating environments epidemic develops out of the natural center. With temperature drop of air lower than 21 ° epidemic stops.
Though the mosquito of Aedes aegypti is widespread in tropical and subtropical zones on all globe. l. was registered only in America, Africa and Europe. On the other hand, in summertime at high temperature the mosquito of Aedes aegypti can appear to S. from tropical zones and at simultaneous delivery of a disease can cause emergence of epidemic fading with the onset of cold weather.
The mosquito of Aedes aegypti lives in the subtropical districts of the USSR, but. l. in our country is not registered.
== Pathogeny ==. l. is an obligate transmissible disease, the expressed blood infection. At infection the virus gets to regional limf, nodes in which breeds; several days later it with a blood flow extends on all organism, affecting a liver, a spleen, kidneys, marrow. The virusemia lasts 3 — 6 days. The patient for lack of a carrier does not represent epid, dangers.
Skin of the patient Zh. l. it is painted in yellow color, it is frequent with the expressed crimson shade in connection with a venous hyperemia. Are most affected a liver where the focal eosinophilic coagulative necrosis of hepatic cells, and kidneys develops: they are increased in sizes, yellowish color, on a section fatty dystrophy is noted. Cortical substance of kidneys indistinctly separates from brain. Multiple hemorrhages in a stomach, intestines, lungs, a pericardium, a pleura and other bodies, dystrophic changes in a muscle of heart, perivascular infiltrates and hemorrhages in a brain are observed.
the Congenital immunity to. l. the person does not possess. Both in South America, and in Africa in endemic districts at almost healthy faces along with diseases latent immunization by small doses of a virus in nature of the local center takes place. The persons who had. l., gain durable lifelong immunity. Inoculative immunity forms, since 7 — the 9th day after an inoculation and at sufficient tension several years remain (to 6).
A clinical picture
the Incubation interval of 3 — 6 days, sometimes to 10 days. In typical cases the disease has a two-wave current with three periods — initial, remissions and reactions. On weight distinguish easy, medium-weight, heavy and fulminant forms of a disease.
Initial, or feverish, the period called also by the period of an active hyperemia lasts 3 — 4 days. The prodromal phenomena usually are absent. The disease begins, as a rule, sharply. There is a severe headache and dizziness, a back pain, extremities. Temperature in the first days reaches 39 — 40 ° above, is followed by a fever. The hyperemia of the person, neck and an upper part of a trunk, a hyperemia of conjunctivas, the expressed injection of vessels of scleras, puffiness of the person, puffiness a century, a swelling of lips, bright red language is objectively noted. Skin dry and hot. Sick eyforichna, are irritable, have sleeplessness. Thirst, nausea, numerous vomiting slime are characteristic. Pulse of 100 — 130 blows in 1 min., the ABP normal, cardiac sounds are muffled. For the 3rd day the condition of the patient worsens, appears cyanosis, jaundice in the form of a subikterichnost or an ikterichnost of scleras, nasal bleedings, bleeding of gums, impurity of blood in the emetic masses having an appearance of a coffee thick is possible, the kcal can be with impurity of blood. The liver and a spleen are a little increased and sensitive at a palpation. From now on bradycardia owing to the expressed intoxication, an oliguria, a leukopenia and an albuminuria comes to light. The type of the patient which received the name «amarilny mask» is characteristic: the person bloated with a crimson-bluish shade, eyes shine, conjunctivas are hyperemic, a photophobia, dacryagogue, bright red color of lips, expression uneasy, scared.
On 4 — the 5th days from an onset of the illness there comes the period of remission (lasting from several hours to 1 days): temperature falls to normal or subfebrile figures, the state considerably improves, head and muscular pains weaken or at all disappear, nausea and vomiting stops.
Remission can be absent, and then at once the initial stage is followed by the period of reaction. At an easy current recovery begins with temperature drop.
Observe medium-weight and heavy forms of a disease more often. In these cases the period of remission is replaced by the period of reaction lasting 3 — 4 days or the period of a venous staz which is characterized by the expressed intoxication and lack of a virusemia. The condition of patients progressively worsens, temperature increases again, the terrible hemorrhagic and icteric syndrome, and also a renal failure with the expressed albuminuria develop; the oliguria can be replaced by an anury, the azotemia is possible. During this period puffiness of the person disappears, the hyperemia of integuments is replaced by pallor with a bluish shade (venous staz), on mucous membranes hemorrhages are noted. Pulse rate 50 and even 40 blows in 1 min., cardiac sounds are muffled, sometimes with systolic noise on a top, the ABP falls, premature ventricular contraction and a collapse are possible. A liver at a palpation plotnovaty, painful. Indicators of bilirubin — direct and indirect raise (see. Hyperbilirubinemia ), zymohexases, aminotransferases, bromsulfoftaleinovy test (see), is registered urobilinuria (see). Hemorrhagic manifestations are most frequent — gastrointestinal bleedings (see); more rare happen nasal bleedings (see), hamaturia (see), hemorrhagic rash. An albuminuria — to 10 g/l and more depending on weight of a disease, in urine granular and hyaline cylinders appear. In blood and in this phase the leukopenia (there are 1500 — 2500 leukocytes in 1 mkl), a neutropenia and a lymphocytopenia, seldom a leukocytosis, a polyglobulia, high hemoglobin and a color indicator is noted, ROE accelerates, coagulability of blood is slowed down. These changes on 6 — the 7th day of a disease are most expressed. Death comes more often from an acute renal failure with development of an uremic coma and toxic encephalitis, is more rare from a hepatic coma or from myocarditis.
Reconvalescence at a medium-weight and heavy current begins approximately with the 10th a disease, the condition of patients improves, there occurs full normalization of all clinical laboratory indicators. The adynamy remains within a week. At an easy form (moderate fever lasts 1 — 3 day) the disease is diagnosed by means of laboratory methods, but it is possible to assume it taking into account epidemiol, situations in the local center. The fulminant form conducts by death on 3 — the 4th day from an onset of the illness. At medium-weight and heavy forms lethal outcomes on 6 — the 7th day of a disease are possible.
Possible complications: pneumonia, parotitis, myocarditis, sometimes gangrene of soft tissues or extremities, abscess of kidneys; there can be encephalitis.
the Diagnosis at most of patients is based on characteristic a wedge, a symptom complex (a typical temperature curve, symptoms of hemorrhagic diathesis, renal defeats, jaundice, bradycardia, increase in a liver and spleen etc.), the account epidemiol, situations (the local centers) and these laboratory researches (a leukopenia, a neutropenia, a lymphocytopenia, a considerable albuminuria, a hamaturia, a bilirubinemia, an azotemia, substantial increase of aminotransferases), allocation of a virus from patients in the first 4 days of a disease, reactions of binding complement (see) and reactions of braking of passive hemagglutinations (see), but in the presence of quadruple increase in antiserum capacities in pair serums, and in special laboratories — and on a neutralization test of a virus (see. Virologic researches ). Serol, tests in dynamics allow to confirm retrospectively the diagnosis since antibodies to them come to light only from the 2nd week of a disease. At a lethal outcome the liver where the centers of a submassive and massive necrosis of hepatic segments and acidophilic little bodies of Kaunsilmen come to light is histologically investigated.
Differentiate. h.p. flu (see), a severe form of a viral hepatitis (see. viral hepatitis ), ikterogemorragichesky hay fever (see), malaria (see), fever dengue (see), flebotomny fever (see), tick-borne typhinia (see), with Crimean hemorrhagic fever (see), hemorrhagic fever of Lass (see. Lassa fever ).
At flu the acute onset of the illness is followed strong local (usually in a forehead and temples) by a headache, muscular pains, sharply expressed toxicosis, an adynamia, a dermahemia of the person and neck, frequent bradycardia and a leukopenia with a neutropenia. There is no hamaturia, a bilirubinemia, an azotemia and as considerable, as at. l., albuminurias; the spleen does not increase.
The severe form of a viral hepatitis is characterized by a gradual course of a disease, there is no hamaturia, the albuminuria is poorly expressed (feverish), the kcal becomes colourless that is not observed at. l. It is necessary to consider epid, the anamnesis (the local centers for. l.).
(Vasilyev's disease — Veylya) are characteristic of an ikterogemorragichesky hay fever the acute beginning, increase in residual nitrogen, the Meningeal phenomena, a neutrophylic leukocytosis is frequent with two-phase fever, muscular pains, especially gastrocnemius muscle pains, a gepatorenalny syndrome with jaundice and nephritic symptoms (a proteinuria, a hamaturia, granular cylinders). The anamnesis — possible contact with rats, bathing in ponds and other reservoirs infected with leptospira is considered epid. In the first days of a disease at a mikroskopirovaniye of urine in a dark field it is possible to find leptospira. After the 10th day of a disease there is positive an agglutination test.
Severe forms of malaria differentiate from. l. on the basis of detection in a thick drop of plasmodiums.
The acute onset of the illness with high temperature and severe pains in joints of extremities without their swelling is characteristic of fever of the Dengue. There can be korepodobny or scarlatiniform rash on a hyperemic background of skin, especially persons. The spleen does not increase, there is no jaundice, there is no bilirubinemia, a proteinuria, a hamaturia and an azotemia.
Flebotomny fever proceeds sharply and quickly with positive symptoms of Peak (an injection of vessels of scleras at outside corners of eyes in the form of triangles with top at a cornea), Taussiga (morbidity during the pressing on eyeballs and at the movement a century), severe muscular pains, especially in a waist and shins, sometimes with joint pains. The liver and a spleen are not increased, urine without changes, is not present a bilirubinemia.
The tick-borne typhinia is diagnosed after detection of spirochetes in smears or in a thick drop of blood.
At the Crimean hemorrhagic fever often there are enantema, petechias, ekhileoza, the liver and kidneys seldom is surprised. Intrahospital cases of infection of medical staff after contact with blood of the patient are possible. The final differential diagnosis is made by results virusol, and serol, by inspections.
Hemorrhagic fever of Lass differs from. l. in an onset of the illness by outward of the patient (an edematous, pale face with increased cervical limf, glands). At hemorrhagic fever of Lass are less frequent went. - kish. bleedings and hemorrhagic rash, jaundice, as a rule, is very rare intrahospital cases of infection, higher lethality are noted. It is differentiated also by results virusol, and serol, inspections.
Etiotropic treatment. l. no. Treatment by serum from convalescents, from naturally immunizirovanny monkeys and horses does not give effect. Therefore at easy forms appoint a symptomatic treatment. In treatment of medium-weight forms use redoxon, Vikasolum, drugs from group of citrin, cardiovascular means. At a heavy and fulminant current carry out intensive or even resuscitation therapy: use of high doses of glucocorticoid hormones, hemotransfusion and blood-substituting liquids, Polyglucinum, Ringer's solution — Locke or Phillips's solutions (for fight against a metabolic acidosis), vazopressor and cardiac glycosides; for removal of vomiting intramusculary or intravenously enter hypertensive (10%) solution of sodium chloride. At emergence of a renal coma the hemodialysis is shown. Antibiotics are appointed at emergence of complications (pneumonia, parotitis etc.).
the Forecast at an easy form Zh. l. always, and at a medium-weight current it is almost always favorable. A severe form of a disease it is frequent, and fulminant always comes to an end with death. The lethality depending on character of epidemic fluctuates from 1 to 25% and above. E.g., in Nigeria in 1970 in one district the lethality fluctuated from 1,6 to 14,4%, and in another, on 193 km to the south, it made 45,6%; in the State of Goias (Brazil) during the outbreak of a disease in December, 1972 — April, 1973 from 63 diseased 39 died.
Strict epidemiol, observation in the territory where the disease is registered or registered in the past. l.; immunization of the population against. l.; systematic work on implementation among locals of individual and collective measures of protection against attack of mosquitoes (a zasetchivaniye, a pologization, use of repellents) and fight against mosquitoes; isolation of the persons arriving from places where there are cases. l., and not immunizirovanny against. l.; disinsection of the airplanes which arrived from places unsuccessful on. l.; planned works on destruction of mosquitoes — carriers of a virus Zh. l.
Long-term broad actions for destruction of mosquitoes — carriers of an infection are very effective at epidemic. l. Only destruction of a mosquito leads to effective decrease in incidence and elimination of epidemic.
So, in Brazil long-term destructive works led to elimination of this disease. At local. l. forest mosquitoes are almost almost unavailable in the plan not only their full destruction, but also noticeable decrease in their number. In this case the leading role belongs to mass immunization of the population, and first of all impart people who are connected with stay in the woods.
Apply two types of live vaccines to immunization of people: from the strain 17D received by Teyler (M. Theiler) at long browning of a virus Zh. l. in culture of fabric, and from the fr. neytropny strain Dakar received at long intracerebral passages of a virus on white mice.
In the USSR the vaccine from a strain 17D on chicken embryos is produced and applied. Antibodies appear in 7 — 10 days after vaccination and are found in blood many years. The vaccine is issued in the form of powder (in ampoules); before introduction the vaccine is dissolved in fiziol, solution (1:10) and enter 0,5 ml under skin.
Reaction to an inoculation is insignificant, no more than at 5% vaccinated. The indisposition, a headache, small temperature increase can be noted. Extremely seldom as the complication is observed encephalopathy, is more often at use of a vaccine from a strain Dakar. Vaccination against. l. — very effective action.
During the developing of a disease of patients. l. reveal and hospitalize and urgently inform bodies of health care. Epid, the center is inspected for the purpose of identification of the place, time and circumstances under which there was infection of the patient. Carry out serol. inspection (definition of specific antibodies in blood) all persons which were in the center. Actively reveal and laboratory inspect the persons having at least slight feverish diseases. Broad disinsection works and a delarvation of places of breeding of a mosquito will urgently be organized. Universal immunization of the population is carried out.
The international actions against delivery. l.: the cable notice of WHO the country where the disease is for the first time brought, or the country, through to-ruyu delivered the patient, or the country, earlier free from. l., where the first local disease is registered; disinsection of the ships, airplanes and the land transport arriving from areas where it is registered. l.; a seven-day karantinization of the monkeys and other animals brought from zones unsuccessful on. l.; compulsory vaccination of the persons leaving places adverse on. l., or going there, with delivery imparted certificates on vaccination against. l., which are valid from the 11th day after an inoculation.
Bibliography: Jones E. M and Wilson D. C. Features of a course of yellow fever at the persons sent to Vomsky Christian hospital in the period of epidemic of 1969 on Dzhoye's plateau in Nigeria Bulletin WHO, t. 46, No. 5, page 632, 1973, bibliogr.; Laboratory diagnosis of viral and rickettsial diseases, under the editorship of E. Lennet and N. Schmidt, the lane with English, M., 1974; The Multivolume guide to microbiology, clinic and epidemiology of infectious diseases, under the editorship of H. N. Zhuko-va-Verezhnikova, t. 8, page 375, M., 1966, bibliogr.; Monath T. River, etc. Epidemic of yellow fever around Ok-voga, the state of Benue Plateau, Nigeria (1970), Bulletin WHO, t. 49, No. 2, page 125, 1974, bibliogr.; Rudnev G. P. Clinic of quarantine infections, M., 1972; The Guide to laboratory diagnosis of viral and rickettsial diseases, under the editorship of P.F. Zdrodovsky and M. I. Sokolov, page 413, M., 1965.
M. P. Chumakov, K. M. Loban.