What is Lassa Fever?
Lassa fever is an acute zoonotic disease from the group of viral hemorrhagic fevers with symptoms of universal capillary toxicosis, liver, kidney, CNS damage. Clinically manifested by fever, hemorrhagic syndrome, the development of renal failure. Treats especially dangerous virus infections of Africa with a high lethality.
The disease was first registered in 1969 in the town of Lassa (Nigeria). Three of the first five cases of the disease in nurses and researchers have been fatal. The pathogen was isolated in 1970. Lassa fever is widespread in West Africa (Sierra Leone, Nigeria, Liberia, Guinea, Senegal, Mali), some Central African countries (Central African Republic, Burkina Faso). Imported cases of infection have been registered in Europe, the USA, Japan, and Israel.
According to some studies, between 300,000 and 500,000 cases of Lassa fever occur annually in West Africa. The overall mortality rate is 1%, and among hospitalized patients it is up to 15%. Death usually occurs within 14 days of the onset of the disease. The disease is especially severe in women in late pregnancy – during the third trimester of pregnancy, the mother’s death and / or fetal death occurs in more than 80% of cases.
Causes of Lassa Fever
The causative agent of Lassa fever is an RNA-genomic virus of the genus Arenavirus of the Arenaviridae family. It has a common antigenic structure with pathogens of lymphocytic choriomeningitis, Argentinean and Bolivian fevers. The spherical virion, 70-150 nm in diameter, has a lipid membrane, on which the villi are often club-shaped, about 10 nm long, contains RNA. When electron microscopy inside the virus particles revealed about 10 small dense granules (ribosomes), resembling sand (Latin. Arenaceus, sandy), whence it was given the name of the family of viruses. Currently, 4 subtypes of Lassa virus have been isolated, circulating in different regions. The virus is resistant to environmental factors; its infectivity in serum or secretions does not decrease for a long period without special treatment. Inactivated by fatty solvents (ether, chloroform, etc.).
The reservoir and source of infection is the multi-horned African rat Mastomys natalensis (in epidemic foci, the infection may reach 15-17%) and, probably, other mouse-like rodents. In rodents, the infection can occur for life in the form of asymptomatic persistence of the virus. Animals release the virus with saliva and urine for up to 14 weeks. The source of infection can also be a sick person during the whole illness; however, all secretions may be contagious.
The transmission mechanism is varied. The transfer of the virus between rodents is realized by contact: when drinking and eating food contaminated with urine of rat virus carriers. Infection of people in natural foci occurs by chance during the hunt (by stripping the skins), when drinking water from urine-infected sources, thermally unprocessed meat. Infection can occur at home in the presence of rodents in their homes. The virus penetrates through the respiratory system, damaged skin, conjunctiva, gastrointestinal tract. A sick person is dangerous to others throughout the illness. Transmission of the virus among people is realized by airborne, alimentary, contact and sexual ways. Vertical transmission of the virus from the pregnant to the fetus is also possible. Hospital-acquired outbreaks of Lassa fever have been recorded. The latter were associated with pharyngitis and lesions of the mucous membrane of the upper respiratory tract in patients who emit large doses of the virus when they cough. Also reported cases of infection of medical personnel from the tools infected with blood – during surgical operations and autopsy of the dead or conducting experiments on animals.
Natural susceptibility of people. Lassa fever – a disease with an average level of contagiousness, but high mortality (up to 40% or more). Immunity is almost unexplored, but those who have been ill have specific antibodies for 5-7 years.
Major epidemiological signs. Lassa fever is a natural focal viral disease. At risk include the population living in West Africa. At the same time, the high population density of rodents of the genus Mastomys makes the disease endemic in both rural and urban areas. Mortality in Lassa fever varies from 18.5 to 60%. Secondary cases of the disease in the epidemic are usually less dangerous than the primary ones. In most endemic areas, it is recorded year-round. The highest incidence rate is in January-February during the period of rodent migrations to human habitation. The disease can be delivered to non-endemic countries. In particular, the delivery of infection to New York, London, Hamburg, Japan, and the United Kingdom took place. Like other hemorrhagic fevers, Lassa fever is subject to strict accounting and control internationally.
Lassa fever is affected by people from all age groups, both men and women. People living in rural areas where the Mastomys usually live are most at risk, especially in areas with poor sanitation or in densely populated areas. Health workers are at risk of disease in the absence of adequate barrier protection and infection control during patient care.
Pathogenesis during Lassa Fever
In accordance with the dominant pathways of transmission, the entrance gates of infection are mainly the mucous membranes of the respiratory tract and gastrointestinal tract. During the incubation period, the virus multiplies in the regional lymph nodes, followed by persistent and severe viremia, accompanied by fever and dissemination of the pathogen to the organs of the reticulohisocytic system. Virus-infected cells of vital organs become targets for cytotoxic T-lymphocytes. Further, the formation of immune complexes and their fixation on the basement membranes of cells lead to the development of severe necrotic processes in the liver, spleen, kidneys, adrenal glands, myocardium. At the same time, inflammation is mild, and there are no changes in the brain.
It has been established that in the febrile period of the disease, the production of neutralizing antibodies is delayed. Presumably, in the development of a severe infectious process with an early fatal outcome, disturbances of cellular immune responses play a leading role.
In patients with Lassa fever, specific antibodies are detected in the serum. In endemic areas, antibodies are found in 5-10% of the population, whereas only 0.2% of the population showed clinical signs of the disease. This indicates the possibility of asymptomatic or mild disease that remains undetected. Repeated illness with Lassa fever is not observed. There is no data on the duration of immunity.
Symptoms of Lassa Fever
The incubation period varies from 6 to 20 days. The disease often begins gradually with low fever, accompanied by malaise, myalgia, sore throat when swallowing, symptoms of conjunctivitis. After a few days, as body temperature rises to 39–40 ° C, weakness, apathy and headache increase with chills, and significant pains in the back, chest and abdomen appear. Nausea, vomiting and diarrhea (sometimes in the form of melena), cough, dysuric phenomena, convulsions are possible. Sometimes there is a visual impairment.
When examining patients pay attention to the pronounced hyperemia of the face, neck, skin of the breast, hemorrhagic manifestations of various localization, exanthema petechial, maculo-papular or erythematous character. Peripheral lymph nodes are enlarged. Ulcerative pharyngitis develops: white spots appear on the mucous membrane of the pharynx, soft palate, tonsils, which later turn into ulcers with a yellow bottom and a red rim; often ulcers are localized on the palatine arches. Heart sounds are muffled considerably, bradycardia and arterial hypotension are noted.
An objective examination of the patient early detected generalized lymphadenopathy, more pronounced increase in cervical lymph nodes. At the end of the 1st week, rash appears. Along with hemorrhages in the skin of various sizes, there are other elements (roseola, papules, blemishes), sometimes the rash resembles a measles rash. Relative bradycardia, and sometimes pulse dicrotism, is noted; later, with the development of myocarditis, bradycardia is replaced by tachycardia. Borders of the heart are expanded, muffled heart sounds, blood pressure lowered. Shortness of breath, cough, stabbing pains in the side, shortening of percussion sound, dry and moist rales, and sometimes pleural friction are noted; radiological infiltrative changes are revealed, often pleural effusion.
Expressed changes in the digestive system. In addition to early appearing necrotic pharyngitis, pain in the epigastric region, nausea, vomiting, rumbling and pain in the umbilical region, watery abundant stools. The liver is enlarged, painful on palpation. Sometimes ascites develops. From the nervous system – severe headache, meningeal symptoms (with normal composition of cerebrospinal fluid), disorders of consciousness, dizziness, tinnitus; complete hearing loss may occur. In the period of recovery, asthenia persists for a long time, hair loss is observed.
In the study of peripheral blood leukocytosis with a shift of the leukocyte formula to the left, thrombocytopenia, a decrease in the content of prothrombin, the activity of aminotransferases increases; positive thymol test, with renal insufficiency, the urea content in the blood rises. In the study of urine characteristic proteinuria (often more than 2 g / l), cylindruria.
In severe cases of the disease (35-50% of cases), clinical signs of multiple organ lesions appear – liver, lungs (pneumonia), heart (myocarditis), etc. capillaries. Infectious toxic shock, acute renal failure develop. In these cases, at the beginning of the 2nd week of illness, death is often observed.
With a favorable course of the disease, an acute febrile period can last up to 3 weeks, the body temperature decreases lytically. Recovery is very slow, possible relapses of the disease.
- infectious toxic shock,
- acute renal failure,
In severe forms of the disease mortality is 30-50%.
Diagnosing Lassa Fever
Great clinical importance in the formulation of a preliminary diagnosis is given to a combination of fever, ulcerative pharyngitis, swelling of the face and neck (in the midst of the disease), albuminuria and other changes in the urine. Differential diagnosis is difficult, especially in the early phase of the disease.
Laboratory diagnosis. In the hemogram, leukopenia is noted, later it is replaced by leukocytosis and a sharp increase in ESR (40-80 mm / h). Clotting of blood decreases, prothrombin time lengthens. Proteins, leukocytes, erythrocytes, granular cylinders are detected in the urine.
Special laboratory methods include isolating the virus from pharyngeal swabs, blood and urine and identifying it. As a method of rapid diagnosis, ELISA and REIF are used, which detect virus antigens. For the determination of antiviral antibodies use phaa, RAC. According to the WHO recommendation, in the presence of IgG in titers of 1: 512 and higher with simultaneous detection of IgM in febrile patients in endemic areas, a preliminary diagnosis of “Lassa fever” is made.
Lassa Fever Treatment
Hospitalization of patients in specialized infectious departments with a strict isolation regime is obligatory. Bed rest, treatment is mainly symptomatic. Use of plasma of convalescents is effective only in some cases when administered in the first week of the disease. With its introduction at a later date, the patient may deteriorate. In case of complications, antibiotics, glucocorticoids are indicated. Etiotropic agents and vaccines are being developed. The use of ribavirin (virazole, ribamidil) in the early phase of the disease orally at 1000 mg / day for 10 days or intravenously for 4 days reduces the severity and mortality.
Prevention of Lassa Fever
Preventive measures are mainly reduced to combating the entry of rats into the homes – sources of infection. Particularly should be protected household items and food products from contamination by urine of rodents or dust containing their excrement. Personnel caring for patients, taking away infected material from patients, or participating in surgical operations should be trained in the care of particularly infectious patients. Hospital premises should be maintained in compliance with a strict anti-epidemic regime. Specific prevention is not developed.
Activities in the epidemic outbreak. In the event of a disease, organizational quarantine measures are important: isolating patients in boxes, wearing anti-plague suits by staff, hospitalization of contact persons in insulators, burning sick things (of no value), burning dead bodies. Persons arriving from endemic areas for Lassa fever, if they have any fever, are isolated in hospitals for diagnosis. In the outbreak carry out the current and final disinfection.