Laos fever

Laos fever is an acute zoonotic natural-focal viral disease from a group of particularly dangerous viral infections in Africa. Characterized by the phenomena of universal capillarotoxicosis, liver, kidney, central nervous system, high lethality. Symptoms of Laos fever: fever, hemorrhagic syndrome, the development of renal failure.

The first five cases of the disease reported and described in the town of Lassa (Nigeria) in 1969, nurses and researchers (three cases have been fatal). The causative agent was isolated in 1970. Currently, Lassa fever is widespread in West and Central Africa (Sierra Leone, Nigeria, Liberia, Guinea, Senegal, Mali, Central African Republic, Burkina Faso). Registered import cases of infection in the US, Europe, Israel, Japan.

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Epidemiology of the Laos fever

The reservoir and source of infection are African rats of the genus Mastomys (M. Natalensis, M. Huberti, M. Erythroleucus), whose infection in epidemic outbreaks can reach 15-17%. Infection in rodents can occur for life in the form of chronic asymptomatic persistence of the virus, which is released with saliva, faeces and urine. Sources of infection include sick people, whose contagiousness persists throughout the period of the disease; with all the allotments of a person being infectious.

The mechanism of transmission of Laos fever is diverse. In rodents, the virus is transmitted by drinking and eating food contaminated with the urine of the virus-carrying rats, and also by the vertical pathway. Infection of people in natural foci and at home is possible with the use of water and products infected with urine of rats, contact-household way through household items, when ripping the skins of killed animals. The ability of the virus to penetrate the human body through respiratory organs, damaged skin, mucous membranes, gastrointestinal tract causes the transmission of infection in various ways - airborne, alimentary, contact, sexual, vertical.

[2], [3], [4],

The natural susceptibility of people

Fever Lassa - a disease with an average level of contagiousness, but high mortality (18 to 60%). In most of the endemic regions of Africa, it is recorded year-round, with a slight rise in morbidity in January-February (the period of migration of rodents to human habitation). Immunity has been studied little, but specific antibodies persist in those who have recovered within 5-7 years.

Major epidemiological signs of Laos fever

The highest incidence is observed among the population living in West Africa. The disease is endemic both in rural areas and in cities, which is explained by the high density of the rodent population of the genus Mastomys. Often there are secondary cases of infection (infection from one patient), but a further chain of transmission of the virus is possible. Registered import cases of infection in New York, Hamburg, Japan, Great Britain.

A special group of risk is made by health workers. Infection can occur through various biological secrets of the patient, a blood-infected medical toolkit, as well as aerogenic from patients who emit large portions of the virus when coughing. Known nosocomial outbreaks of Lassa fever in Liberia, Nigeria and other countries.

Causes of Laos fever

Laos fever is caused by arenaviruses, which belong to the family of RNA-containing non-enveloped viruses. The family Arenaviridae received its name from the Greek. arenosa - sandy (due to the presence in the virion of ribosomes, similar to grains of sand). The family includes the virus of lymphocytic choriomeningitis, as well as the viruses Lassa, Junin, Machupo, Guanarito, causing severe hemorrhagic fevers.

Characteristics of haemorrhagic fevers of the Arenaviridae family

Name of the virus	Name of the disease	Spread	Natural reservoir
Lassa	Lassa fever	West Africa (especially Sierra Leone, Guinea, Nigeria)	Mastomys huberti, Mastomys erythroleucus Mastomys, natalensis
Junin	Argentinean GL	Argentina	Calomys Musculinis
Machupo	Bolivian GL	Bolivia	Calomys callosus
Guanarito	Venezuelan GL	Venezuela	Zygodontomys brevicauda
Sabia	Brazilian GL	Brazil	Unknown

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Structure and reproduction

The virion has a spherical or oval shape and a diameter of about 120 nm. Outside, it is surrounded by a membrane with clove-shaped glycoprotein spines GP1 and GP2. Under the membrane there are 12-15 cell ribosomes, similar to grains of sand. The capsid has a spiral shape. The genome is represented by two segments (L, S) of single-stranded minus-RNA; it encodes 5 proteins, in particular L-, Z-, N-, G-proteins. The virion contains transcriptase (L-protein, RNA-polymerase). Reproduction is carried out in the cytoplasm; After assembly and incorporation into the virion of ribosome-like particles, its budding through the plasma membrane of the cell occurs.

Resistance

Arenaviruses are sensitive to the action of detergents, UV and gamma radiation, to heating and are insensitive to freezing and lyophilization.

Cultivation

Arenaviruses are cultured in chicken embryos, in rodents and in cell culture, for example, Kshkulture kidney cells of green monkeys.

In recent years, several other viruses belonging to this family have been identified in Africa, South and North America (Mopeia, Mobala, Ippy, Amapari, Flexal, Cupixni, Tamiami, Bear Canyon), but their role in human pathology has not yet been established. According to experts, every three years a new virus of this family is found.

The natural susceptibility of people to arenaviruses is high, and immunity is persistent and prolonged.

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The pathogenesis of Laos fever

The Laos fever has not been studied enough. Models for studying the mechanisms of infection are rodents and monkeys of various species.

The entrance gates of the virus are most often the mucous membranes of the respiratory and digestive tract. In the incubation period, the pathogen actively multiplies in the regional lymph nodes, after which persistent and pronounced viralemia develops with dissemination of the virus through the organs of the mononuclear-phagocytic system. An important pathogenetic role of MFS in the development of the disease has been established. When a virus of monocytes is affected, a significant release of cytokines (TNF, IL-1,6, etc.) occurs; with the latter associated the occurrence of polyorganic pathology, impaired vascular permeability (damage to the endothelium), development of DIC syndrome, infectious-toxic shock, collapse. Cells of vital organs infected with a virus become a target for cytotoxic T-lymphocytes. As a result of the formation of immune complexes and their fixation on the basement membranes of cells, severe necrotic processes develop in the liver, spleen, kidneys, adrenals, myocardium. Inflammatory phenomena in this case are poorly expressed, changes in the brain are not detected.

The delayed nature of the production of virus neutralizing antibodies and the disturbance of cellular immune responses in the acute febrile period of the disease are presumably the cause of the development of a severe infectious process with an early lethal outcome. At the autopsy of the dead patients, significant blood filling in the spleen, liver, red bone marrow attracts attention.

Symptoms of Laos

The incubation period of the Laos fever usually lasts 7-12 days, with possible fluctuations from 3 to 16 days.

Most cases of Lassa fever occur as an erased or subclinical form.

In cases of moderate severity, Laos fever often begins gradually with a low fever, malaise, myalgia, sore throat, swallowing, conjunctivitis. A few days later, typical symptoms of Laos fever are noted: body temperature (with chill) rises to 39-40 ° C, headache, weakness, apathy develops. 60-75% of patients report significant pain in the retro-intestinal and lumbar regions, in the back, chest, somewhat less often in the abdomen. Often (in 50-60% of cases) there are coughing, nausea, vomiting. Possible diarrhea (sometimes in the form of melena), dysuric phenomena, convulsions. Part of the patients develop a visual impairment. When examining patients, attention is drawn to the hyperemia of the face, neck and skin of the breast, sometimes swelling of the face, manifestations of hemorrhagic syndrome of different localization, exanthema of the petechial, maculopapular or erythematous nature, peripheral lymphadenopathy. Also develop angina (in 60% of cases), less often - ulcerative pharyngitis: on the mucous membrane of the pharynx, soft palate, arches, tonsils appear white spots, later turning into ulcers with a yellow bottom and a red rim, often localized on the arches. Heart sounds are significantly muted, bradycardia and arterial hypotension are noted. An acute febrile period can last up to 3 weeks, the temperature decreases lytically. Recovering is very slow, relapse of the disease is possible.

Severe course (35-50% of cases) is characterized by the symptoms of polyorganism lesions - liver, lungs (pneumonia), heart (myocarditis), etc. CNS lesion can manifest itself with the development of encephalopathy, encephalitis, meningitis (serous). Especially serious illness occurs in children younger than 2 years old, with frequent development of hemorrhagic syndrome, bleeding. The following clinical signs are prognostically unfavorable: hypotension (shock, colapsus), severe haemorrhagic syndrome (bleeding), oligo- and anauria, edema of the face, development of pulmonary edema, ascites, myocarditis, significant increase in ALT, high level of viremia, determined in PCR. In case of unfavorable course of the disease at the beginning of the second week of the disease, lethal outcomes are often observed.

Complications of Laos fever

Laos fever can be complicated by infectious-toxic shock, pneumonia, myocarditis, acute renal failure, delirium. At the 2-3 nd week of the disease, pericarditis, uveitis, orchitis, as well as complications associated with cranial nerve damage (more often 8 couples - deafness) are possible. In severe forms of the disease, the mortality rate is 30-50%. Mortality of hospitalized patients is from 15 to 25%.

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Diagnosis of Laos fever

Differential diagnosis of Laos fever is difficult, especially in the early phase of the development of the Lassa fever. When setting a preliminary diagnosis, a great clinical importance is attached to a combination of fever, retrosternal pain, ulcerative pharyngitis, and proteinuria. This combination of symptoms is observed in 70% of patients and allows clinically to suspect the disease.

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Laboratory diagnostics of Laos fever

Characteristic changes in the hemogram: leukopenia, and in the future - leukocytosis and a sharp increase in ESR (up to 40-80 mm per hour), a decrease in clotting time, prolongation of prothrombin time. The characteristic changes in urine are proteinuria, cylindruria, an increase in the number of leukocytes and red blood cells.

From the first days of the disease, it is possible to isolate the virus from pharyngeal swabs, blood and urine. As an express diagnostic method, ELISA is used (detection of the virus antigen or detection of IgM antibodies). Further, to determine the antiviral antibodies used by the RNGA, RSK. On the recommendation of WHO, a preliminary diagnosis of "Lassa fever" is placed in febrile patients in endemic areas in the presence of IgG antibodies in titers 1: 512 and above and simultaneous detection of IgM. The method of PCR diagnostics is also developed.

Treatment of Laos fever

Obligatory hospitalization of patients in specialized infectious departments with strict isolation and bed rest. Pathogenetic treatment of Laos fever is aimed at correction of metabolic disorders (metabolic acidosis), recovery of circulating blood volume, relief of hemorrhagic syndrome. Assign symptomatic means, with the development of complications, antibiotics, glucocorticosteroids can be used. The effectiveness of the use of plasma convalescents is doubtful: a positive effect is observed only in some cases with the appointment in the first week of the disease, and when it is introduced at a later date, the patient's condition may worsen. The use of ribavirin in the early phase (before the 7th day of the disease) can reduce the severity of the disease and reduce the lethality to 5%. The drug is administered orally at 1000 mg / day for 10 days or intravenously. When administered intravenously, the initial dose is 30 mg / kg of body weight, then ribavirin is administered at 15 mg / kg body weight every 6 hours for 4 days, and for the next 6 days - 7.5 mg / kg body weight every 8 hours. Etiotropic drugs and vaccine preparations are being developed.

How is the Laos fever prevented?

Prevention of Laos fever is reduced to the control of penetration into the dwellings of rats - sources of infection, protection of food and household items from contamination by feces of rodents or dust. Medical personnel should be trained in the rules for working with particularly contagious patients and adherence to strict anti-epidemic regimens. Lassa fever prevented the use of ribavirin 500 mg orally every 6 hours for 7 days. Specific prophylaxis is not developed.