Hemorrhagic fever Lassa( GL Lassa) - Causes, symptoms and treatment. MF.

One of the group of especially dangerous infections, along with the fevers of Ebola and Marburg, includes hemorrhagic fever Lassa. Infection is also a natural focal with endemic zones in tropical African countries.

Lassa hemorrhagic fever is an acute natural focal viral infectious disease characterized by severe intoxication, ulcerative necrotic pharyngitis, affection of many organs and systems, development of hemorrhagic syndrome and severe complications, sometimes incompatible with the life of patients.

Historical and geographical distribution of GL Lassa

The infection got its name from the city of Lassa( Nigeria), where it was first discovered in 1969.The countries of West Africa are endemic in GL Lassa, here up to 500 000 cases of this disease are registered annually. These are Nigeria, Guinea, Mali, Sierra Leone, Senegal, Mozambique, less often Central Africa( CAR, Burkina Faso and others).Mortality with GL Lassa to 60%( an average of about 40%), occurs at the end of the 2nd week of the disease. In case of infection of a pregnant woman, fetal death occurs in 85% of cases.

One of the latest outbreaks of GL Lassa occurred in 2012 in Nigeria. Out of 623 cases, 70 people died( lethal 11%).During the outbreak, many medical workers were engaged in caring for and treating patients.

Causes of Lassa Fever

The causative agent of is the Lassa virus, which belongs to the Arenaviridae family. With electron microscopy, up to a dozen ribosomes resembling sand are visible( in Latin, sandy - arenaceus).The virion contains a single-stranded RNA, a lipid shell, has a diameter of up to 150 nm, a spherical shape with the villi located on the surface. Lassa virus belongs to the first class of danger of infectious agents( that is, it represents both individual and social danger).There are 4 subtypes of the Lassa virus circulating in different regions of Africa.

GL Lassa,

virus Lassa virus is stable in the environment, however it is sensitive to disinfectants( chloroform, ether).In the secretions of animals and a sick person, the virus can persist for a long time.

Source of infection in endemic foci is a multi-nosed African rat( Mastomys natalensis), which not only inhabits the steppe zone, but is also capable of penetrating human habitation. Up to 17-19% of rats are infected in natural foci. In the body of animals, the infection is more often asymptomatic, but for a long time the virus persists and is excreted in the urine and saliva of rodents.

Source of infection GL Lassa - the multi-necked African rat

A sick person is a danger to others. The virus is contained in the nasopharyngeal contents, blood, urine, and patient's saliva, and because long periods of time can persist in the dried state, the transmission factors that can cause discharge of the patient( food, water, dishes, dust particles on household items) are also dangerous. The blood of patients is the most dangerous, and along with it, vomit masses with an admixture of blood, sputum with blood.

Mechanisms of infection.

1) Contact-household mechanism in case of blood and discharge of the patient to the damaged skin and mucous membranes.
2) Parenteral mechanism with the use of reusable instruments, insufficient processing of medical instruments, accidental puncture of the needle from sick medical staff.
3) Alimentary mechanism( food and waterway) when the discharge of the patient for food and water. Dangerous is the insufficiently thermally processed contaminated meat of animals, water from infected sources.
4) Aerogenic mechanism( airborne and airborne) when contaminated with infected discharges of the patient - sputum or dust particles enter the respiratory tract.
5) Sexual transmission.

Sensitivity to GL Lassa is high, both adults and children become ill regardless of gender. Known nosocomial outbreaks of Lassa fever. Seasonality is absent, the incidence is recorded evenly throughout the year.

Immunity after the infection is persistent, prolonged( up to 10 years and more), repeated cases of the disease are not registered. Among the local population, up to 15% tolerate the infection asymptomatically.

Pathogenic effect of the Lassa virus on the human body

1) The entrance gates of the infection( according to the routes of infection) can be mucous membranes of the eyes, respiratory tract, digestive tract, reproductive system, microtraumed skin. There are no changes in the entrance gates, but there is a clear relationship between the development of the primary lesion of a particular organ and system, depending on the site of the virus. For example, during the introduction through the mucosa of the digestive system, signs of lesions of the gastrointestinal tract are more often noted, and when inserted through the respiratory tract, lung inflammation, pulmonary edema and the like.

2) Then the virus penetrates into the blood( viremia, toxemia) and spreads throughout the body( hematogenous dissemination) with the defeat of many organs and systems.

3) The main point of application or target is the endothelium of the blood vessels( the inner wall of the vessels).The result of exposure to the Lassa virus is an increase in the fragility of vessels of different calibers that are accompanied by changes in hemostasis, the triggering of the DIC syndrome( disseminated intravascular coagulation syndrome), which the patient will have hemorrhagic rash on the body, hemorrhages and bleeding( the process may involve the intestine, myocardium,lungs, brain, kidneys, liver and other organs).

4) The maximum severity of GL Lassa leads to complications( infectious-toxic shock, acute liver failure, acute adrenal insufficiency, and others).At this stage, a fatal outcome may occur.

Clinical Symptoms GL Lassa

The incubation period( from the time of infection until the onset of the first symptoms of the disease) averages 7-10 days, but can be shortened to 3 days or extended to 21 days.

1) The onset of the disease. Difference from other highly infectious fevers( Ebola, Marburg) - the onset of
disease with GL Lassa is relatively gradual. In patients, symptoms of an infectious-toxic syndrome( fatigue, feeling of weakness, weakness, myalgia or muscle pains, headaches) appear against the background of subfebrile temperature( up to 38º).The temperature rises within 3-5 days and reaches its maximum( 40º).Duration of fever about 2 weeks, less often longer. A special feature is the lack of effect from antibacterial drugs. The character of the temperature curve is typical( by the evening a considerable rise, towards morning and at lunch - relief).Prognostically unfavorable sign is a constant fever( almost not reduced).By the fifth day of illness, the sick feel broken, the weakness is so severe that it is difficult to get out of bed, there may be disturbances in consciousness. When the patient is examined, reddening of the face, neck and upper chest, facial sweating, vascular scleral injection( called "hood syndrome" or cranio-cervical syndrome.)

2) The patient is afflicted with several groups of lymph nodes( generalized lymphadenopathy ).Lymph nodes are enlarged in size slightly, but painful, not soldered to each other and surrounding tissue, the skin over them is not changed.

3) One of the symptoms characteristic of the vast majority of Lassa patients is the pharynx. This symptom appears on the 3-4th day of the disease and is characterized by the appearance of pronounced perspiration in the throat, pain when swallowing, dry mouth. When examining hyperemia or reddening of the throat with a pronounced border of this zone, an increase in tonsils, the appearance on the tonsils, arches, soft palate of ulcerative-necrotic elements of grayish color, the formation can gradually merge, occupying a sufficiently large area of ​​throat. Serum fibrous raids can form on the jaundice.

4) Another frequent syndrome of Lassa Fever is gastroenteritis syndrome .By the 5th day of the disease, patients complain of nausea, vomiting, pain in the epigastric region( stomach), dilution of the stool to watery. With severe severity, dehydration may occur, the first sign of which may be thirst, dry mouth, then a decrease in skin tone, blue skin, and subsequently lowering blood pressure, lower diuresis and convulsive muscle twitching.

5) By the end of the first week, the symptoms of of the hemorrhagic syndrome may appear - exanthema - a rash on the body of a hemorrhagic nature( from point petechiae to large ecchymoses).In a number of cases, there appears coripoid exanthema( spotted-papular).

GL Lassa, DIC-Syndrome

6) In severe disease,
is associated with the above symptoms and syndromes, which occur on average 9-11 days after the onset of the disease:
- pneumonia and pulmonary edema( cough, chest pain when coughing, and thenand with breathing, dyspnea, when examined dry and wet wheezing, shortening of percussion sound, radiological reveals infiltrative changes, pleural effusion);
- toxic damage to the myocardium( pulse or bradycardia, pulse necrosis or pulse wave bifurcation during measurement, with myocardial infarction, the pulse becomes frequent - tachycardia, and at examination - muffling of cardiac tones, lowering of arterial pressure);
- toxic liver damage( increase in liver size, pain in the right upper quadrant, changes in laboratory parameters), toxic kidney damage( acute renal failure);
- infectious-toxic shock( at the height of fever a rapid fall in blood pressure, blue or cyanosis of the skin, decreased diuresis);
- infectious-toxic encephalopathy( cerebral edema);
- severe manifestations of thrombotic hemorrhagic syndrome( intestinal or uterine bleeding, hemorrhage to the adrenal glands, hemorrhage in the myocardium, brain).

Each complication can be fatal in a patient with severe Lassa fever.
Lethal outcome occurs on day 7-14 from the onset of the disease in 40% of patients( mean number).
With a favorable outcome, complaints are worried about the patient for 3 to 4 weeks. In the case of a patient recovering up to 1.5 weeks, the subfebrile condition worries( slight fever, asthenia or weakness and fatigue, and cases of increased hair loss are described).

Diagnosis of Fever Lassa

Preliminary diagnosis is made on the basis of:

1) Epidemiological history( presence of natural foci of infection, contact with local residents, contact with rodents, contact with febrile patients, stay in endemic area for 21 days before the onset of the disease).
2) Clinical data( combination of fever, ulcerative necrotic pharyngitis, gastroenteritis, rash and manifestations of hemorrhagic syndrome).
3) Differential diagnosis, which is carried out with hemorrhagic fevers of another etiology( Ebola, Marburg, yellow fever), diphtheria of throat, streptococcal angina, gastroenteritis of other etiology, HFRS, sepsis, malaria, measles, typhoid fever and others.

The final diagnosis is made using laboratory data:

1) Nonspecific tests: a general blood test( leukopenia, followed by leukocytosis, a decrease in platelets, an increase in ESR to 50-80 mm / h), a decrease in clotting time, biochemistry( increase in ALT,AST, GGTP, decrease of prothrombin, albumin), general urine analysis( proteinuria, erythrocytes, cylinders) and others.
2) Specific studies( conducted in special laboratories for work with infectious agents of hazard class I).Materials for research are swabs from the nasopharynx, blood, urine and others, taken during the first 2 weeks of the disease. Materials are collected in sterile containers, packed, labeled and in metal bixes sent to the laboratory with an attendant. For diagnosis, use the biological method, serological reactions to identify the antigen and antibodies( ELISA, RNIF-express diagnostics for the antigen of the virus Lassa, RNGA, RSK - detection of antibodies).If by 2 weeks from the onset of the disease the antibodies of the acute phase - IgM are absent, then the diagnosis is questioned. On the WHO recommendation, the diagnostic titre of IgG antibodies is a titer of 1: 512.

Treatment of Lassa Fever

1. The organizational-regime measures of include the absolute hospitalization of all suspicious LLs. All caregivers should work in personal protective equipment( type 1 antiplague suit and its modern modifications).The diet is aimed at mechanical, chemical shaking of the patient's body, but is adjusted depending on the leading syndrome.

2. Options for specific therapy. During the work on outbreaks for this infection, therapy of a specific serum or plasma was received from the ill LASS GL in the amount of 250-500 ml once, which should be taken no earlier than 2 months after recovery. Also, ribavirin was suggested as an alternative therapy according to the scheme, inhalation reception of interferon. All specific therapy can be successful in the first 6 days from the onset of the disease.

3. Pathogenetic therapy of includes detoxification( intravenous infusions of glucose-salt mixtures, conduction of forced diuresis), glucocorticosteroids, prevention and treatment of DIC syndrome up to blood transfusion, rehydration( replenishment of fluid) during dehydration, blood flow improving preparationsorgans and systems, hepatoprotectors, vitamin therapy and others.

4. The asynchronous therapy ( with pharyngitis - local treatment, with gastroenteritis - enterosorbents, intestinal antiseptics, probiotics) and others.

GL Lassa, work with patient

With a favorable course of the disease, patients are discharged after clinical recovery, but the disability sheets are prolonged to 4-6 weeks. Examination is not indicated except for residual events.

Prevention of Lassa Fever

- Timely detection of patients with fever and their operative isolation in the boxes of infectious hospitals. Allocation of individual utensils and individual household items. Duration of isolation - not less than 30 days from the moment of the onset of the disease.
- The work of patient service personnel, as well as laboratory staff for research in special protective clothing.
- Determination of the contact circle and quarantine for 21 days( temperature measurement, contact inspection), and if symptoms appear, urgent isolation.
- Emergency prevention includes the appointment of ribavirin 800 mg / day for 10 days.
- Action in the outbreak: cremation of the deceased or burial after disinfection, burning things of the deceased.
- Conducting current and final disinfection in the focus of GL Lassa with the use of special disinfectants.
- Specific prevention is not available.
- Struggle against the penetration of rodents into populated areas( liquidation of landfills, timely repair of dwellings, improvement of social conditions of the population).Deratization in the hearth.
- Information work with the population of the endemic focus.

The doctor infektsionist Bykova N.I.