Marburg virus

American scientists have found a hidden reservoir of the “brother of Ebola” Marburg virus in the body of recovered monkeys. It turned out that the virus hides in the Sertoli cells of the testes, and the infection causes the destruction of their tissue. In a publication in a magazine CellHost&Microbe the authors hypothesized that prompt treatment of filovirus infection would prevent the virus from spreading to testicular tissue and would help prevent subsequent sexual transmission.

The Ebola and Marburg viruses belong to the filovirus family and cause acute hemorrhagic fevers, which on average lead to the death of the patient in half of the cases. In addition, a person who has recovered from the disease can remain a carrier of the virus for a long time - as studies of the second half of the 20th century and the recent Ebola epidemic in West Africa have shown, the Ebola virus is often present in the seminal fluid of men who have had the infection and is detected in semen even after recovery. For this reason, WHO recommended that Ebola survivors abstain from unprotected sex to avoid infecting their partners. The Marburg virus was also detected in the semen of a recovered person, and a case of its sexual transmission was officially registered.

Researchers from the US Army Medical Research Institute of Infectious Diseases found that filoviruses were also detected in the eye and testicular tissues of recovered macaques. In this study, the scientists did not work with the animals themselves, but with archival tissue samples left over from two large experiments. In the first, macaques were infected and then treated with candidate antiviral drugs. As shown by analysis of tissue samples from 97 recovered animals, the Marburg virus was present in the mentioned tissues of a quarter of macaques, and in males it was predominantly found in the testes. Immunofluorescence analysis of testicular tissue against viral glycoprotein showed that the virus is mainly localized in Sertoli cells surrounding the seminiferous tubules.

Immunofluorescent staining of the seminiferous tubules of a healthy animal (left) and one that has recovered from the virus (right) demonstrates that as a result of infection, Sertoli cells detach from the substrate, and the testicular tissue is destroyed. The diagram illustrates the structure of the testis "before" and "after"

Kayla M. Coffin et al / Cell Host&Microbe 2018

The testes are an organ with so-called immune privilege, that is, immune cells have limited access there. Sertoli cells are also involved in the formation of anti-immune protection of spermatocytes. The authors of the work found that infection of Sertoli cells with a virus led to a disruption of the blood-testis barrier in experimental animals, and T-lymphocytes penetrated into the testes. On the one hand, the infiltration of lymphocytes led to the development of inflammation and destruction of testicular tissue. On the other hand, among these lymphocytes they found a significant number of regulatory cells (Treg), which suppress the immune response against the virus, so nothing prevents it from sitting in the testes for a long time. The researchers suggested that immunotherapy targeting Tregs could rid survivors of latent virus.

In the second experiment on macaques, tissue samples of which were analyzed by the authors of the work, the animals were infected with a high dose of the virus and euthanized sequentially from the second to the eighth day of infection. As it turned out, viral RNA is detected in the lymph nodes and spleen already on the second day, but the virus reaches the testes only after seven days. From this observation, the scientists drew an important conclusion that early treatment with candidate drugs can prevent the entry and subsequent persistence of the virus in the testes.

Experiments on mice during the recent Zika virus epidemic showed that Sertoli cells may be a hidden reservoir for this virus. The Zika virus, the epidemic of which has died down in Latin America, belongs to a different family than the Ebola and Marburg viruses. However, despite its relative harmlessness for adults, the virus is dangerous for the developing fetus and also in the sperm of men who have had the infection.

Daria Spasskaya

Ebola hemorrhagic fever

An acute viral, especially dangerous infectious disease characterized by a severe course, severe hemorrhagic syndrome and a high mortality rate.

Pathogen - Ebolavirus sort of Marburgvirus families Filoviridae- one of the largest viruses. The virion has a different shape - filamentous, branching, arachnid, its length reaches 12,000 nm. The genome is represented by single-stranded negative RNA surrounded by a lipoprotein membrane.

The virus consists of 7 proteins. Ebola and Marburg viruses are similar in their morphology, but differ in antigenic structure. Based on the antigenic properties of glycoproteins (Gp), four serotypes of the Ebola virus are distinguished.

The virus is highly variable. Passage in guinea pig cell culture.

Ebolavirus has an average level of resistance to damaging environmental factors (environmental pH, humidity, insolation, etc.).

Epidemiology

The reservoir of the virus is rodents that live near human habitation.

A sick person poses a great danger to others. Mechanisms of pathogen transmission: aspiration, contact, artificial. Routes of transmission: airborne droplets, contact, injection. The virus is found in blood, saliva, nasopharyngeal mucus, urine, and semen. People become infected when caring for the sick; in domestic conditions through hands and household items contaminated with the patient’s blood and urine; through medical instruments and possibly sexually. The risk of intrafamilial infection is 3–17%, with a nosocomial form - more than 50%.

Human susceptibility to the Ebola virus is high; does not depend on age and gender.

Post-infectious immunity is relatively stable. Repeated cases of the disease are rare (no more than 5% of convalescents have been identified). In endemic areas, 7–10% of the population have antibodies to the Ebola virus, which indicates the possibility of developing subclinical or erased forms of the disease.

The distribution area of ​​the virus is Central and Western Africa (Sudan, Zaire, Nigeria, Liberia, Gabon, Senegal, Cameroon, Ethiopia, Central African Republic). Outbreaks occur mainly in spring and summer.

Pathogenesis

The entrance gates for the pathogen are mucous membranes and skin. The virus penetrates the lymph nodes and spleen, where it replicates with the development of intense viremia in the acute period of the disease with multiple organ dissemination. As a result of direct exposure to the virus and autoimmune reactions, a decrease in platelet production occurs, damage to the vascular endothelium and internal organs with foci of necrosis and hemorrhage. The greatest changes occur in the liver, spleen, lymphoid formations, kidneys, endocrine glands, and brain.

Clinical picture

The incubation period lasts 2–16 days (average 7 days).

The onset of the disease is sudden with a rapid rise in body temperature to 39–40 °C, intense headache, and weakness. Characterized by pronounced

dryness and sore throat (feeling of a “rope” in the throat), chest pain, dry cough. On the 2nd–3rd day, abdominal pain, vomiting, and bloody diarrhea (melena) appear, leading to dehydration. From the first days of the disease, facial expression and sunken eyes are characteristic. On the 3rd–4th day, intestinal, gastric, uterine bleeding, bleeding of the mucous membranes, hemorrhages at injection sites and skin lesions, and hemorrhages in the conjunctiva appear. Hemorrhagic syndrome progresses rapidly. On days 5–7, some patients (50%) develop a measles-like rash, after which peeling of the skin occurs. They detect lethargy, drowsiness, confusion, and in some cases, psychomotor agitation. Death occurs on the 8th–9th day from massive blood loss and shock. With a favorable outcome, the febrile period lasts 10–12 days; recovery is slow over 2–3 months.

During the period of convalescence, severe asthenia, anorexia, cachexia, hair loss, trophic disorders, and mental disorders are observed.

Diagnostics

Clinical diagnosis

There are no specific signs to diagnose the disease based on clinical manifestations. Ebola fever should be suspected in cases of acute development of a febrile illness with multiple organ lesions, diarrhea, neurological and severe hemorrhagic manifestations in a patient who was in an endemic area or was in contact with similar patients.

Specific laboratory diagnostics are carried out using virological and serological methods. Isolation of the virus from the blood of patients, nasopharyngeal mucus and urine is carried out by infecting cell cultures; during electron microscopic examination of biopsy samples of skin or internal organs. PCR, ELISA, RNIF, RN, RSK, etc. are used. All studies are carried out in special laboratories with level IV biological safety.

Nonspecific laboratory diagnostics include a general blood test (characteristic: anemia; leukopenia, alternating with leukocytosis with a neutrophil shift; the presence of atypical lymphocytes; thrombocytopenia; low ESR); biochemical blood test (detect increased activity of transferases, amylase, azotemia); determination of the coagulogram (hypocoagulation is characteristic) and the acid-base state of the blood (identifies signs of metabolic acidosis); conducting a general urinalysis (pronounced proteinuria).

Instrumental methods

Chest X-ray, ECG, ultrasound.

Differential diagnosis

The clinical picture of yellow fever is also characterized by an acute onset, severe intoxication with the development of thrombohemorrhagic syndrome. When differential diagnosis of Ebola fever takes into account the following data: stay in an endemic area no more than 6 days before the development of the disease; presence of two-wave fever, insomnia; swelling of the eyelids, puffiness of the face (“amaryl mask”); in the blood - neutropenia, lymphopenia.

With Ebola fever, symptoms of central nervous system damage are more pronounced, diarrhea and vomiting often occur, and catarrhal symptoms rarely develop or are completely absent.

Acute onset of the disease, severe intoxication, and hemorrhagic syndrome are characteristic of both Ebola fever and leptospirosis, but cough, chest and abdominal pain, vomiting, diarrhea, and leukopenia are not characteristic of it.

Mode. Diet

The patient needs strict bed rest and round-the-clock medical supervision.

The diet corresponds to table No. 4 according to Pevzner.

Drug treatment

Etiotropic treatment

Not developed.

Pathogenetic treatment

In epidemic outbreaks, the use of convalescent plasma is recommended. The main therapeutic measures consist of the use of pathogenetic and symptomatic drugs. The fight against intoxication, dehydration, bleeding, and shock is carried out using generally accepted methods.

Lassa hemorrhagic fever

An acute zoonotic natural focal viral disease characterized by the development of hemorrhagic syndrome, ulcerative necrotizing pharyngitis, pneumonia, myocarditis, kidney damage and a high mortality rate.

Pathogen - Lassa virus sort of Arenavirus families Arenaviridae; belong to the LChM/Lassa complex of Old World arenaviruses. It is antigenically related to other arenaviruses (the causative agents of lymphocytic choriomeningitis and HF in South America). The virus has a spherical capsid, with a particle diameter of 50–300 nm, covered with a lipid shell, including glycoproteins (G1 and G2).

The nucleocapsid consists of a protein (N) and RNA, two fragments of which (L and S) encode the synthesis of virion components in the infected cell; There are no hemagglutinins.

Epidemiology

Source and reservoir of the pathogen - rat Mastomys natalensis, living in most African countries near human habitation. The virus has also been isolated from other African rodents ( M. erythroleucus, M. huberti). Animals release the virus into the environment through excreta and saliva.

Mechanisms of pathogen transmission: aerosol, fecal-oral, contact. Routes of transmission: airborne, food, water, contact.

Transmission factors: food, water, and objects contaminated with rodent urine. Infection of people in natural foci can occur by inhalation of an aerosol containing rodent excreta; drinking water from infected sources; insufficiently heat-treated meat from infected animals.

A sick person poses a great danger to others. The main factor of transmission is blood, but the virus is also contained in the patient’s excreta.

Infection occurs through airborne droplets, contact and sexual contact. The virus can be shed by patients for up to a month or more.

Infection occurs through microtraumas when blood or secretions of the patient come into contact with the skin. Cases of illnesses among medical personnel have been recorded when using instruments contaminated with the pathogen, performing surgical operations and dissecting corpses.

Susceptibility is high.

Post-infectious immunity is intense and long-lasting; repeated cases of the disease have not been described.

Pathogenesis

The entry gate for the pathogen is the mucous membranes of the respiratory and digestive organs, damaged skin. At the site of virus introduction, after its primary replication in the lymphoid elements, viremia develops with hematogenous dissemination of the pathogen, damage to many organs and systems. The virus has a tropism for various human organ systems and causes necrotic changes in the cells of the liver, myocardium, kidneys, and endothelium of small vessels, which determines the course of the disease. In severe cases, due to the cytopathic effect of the virus and cellular immune reactions, damage to endothelial cells in combination with impaired platelet function leads to increased “fragility” and permeability of the vascular wall. Profound disorders of hemostasis occur with the development of disseminated intravascular syndrome.

coagulation and consumption coagulopathy.

Clinical picture

The incubation period lasts 3–20 days, most often 7–14 days.

There is no generally accepted classification. There are: mild, moderate and severe course of the disease.

The onset of the disease is subacute or gradual. General malaise, moderate muscle pain and headaches, low fever, and conjunctivitis are detected. During this period, the majority of patients (80%) experience a characteristic lesion of the pharynx in the form of ulcerative necrotizing pharyngitis, as well as enlargement of the cervical lymph nodes. By the end of the first week of the disease, body temperature reaches 39–40 °C; symptoms of intoxication increase; nausea, vomiting, chest and abdominal pain occur; diarrhea develops, leading to dehydration. From the second week, a maculopapular rash may appear; identify hemorrhagic manifestations (subcutaneous hemorrhages, nasal, pulmonary, uterine and other bleeding). Bradycardia and arterial hypotension occur; Possible hearing loss, seizures and focal neurological clinical manifestations. If the course of the disease is unfavorable, swelling of the face and neck occurs, free fluid is detected in the pleural and abdominal cavities, and hemorrhagic syndrome increases. In severe cases, death occurs on the 7th–14th day. In surviving patients, body temperature decreases lytically after 2–4 weeks. Recovery is slow. General weakness persists for several weeks, in some cases hair loss occurs and deafness develops; relapses of the disease are possible.

Clinical diagnosis

Early clinical diagnosis of Lassa fever is difficult due to the lack of specific symptoms of the disease. Of the clinical manifestations, the greatest diagnostic significance is: subacute onset; a combination of fever, ulcerative pharyngitis, hemorrhagic syndrome and renal failure.

Epidemiological data (stay in an epidemic focus) in conjunction with the results of virological and serological studies are of great importance.

Specific and nonspecific laboratory diagnostics

The absolute diagnostic sign of the disease is the isolation of the virus from the blood, throat wash, saliva, urine and exudates (pleural, pericardial, peritoneal) of the patient; and also from the dead - from samples of internal organs. Effective diagnostic methods: ELISA and RNIF. The diagnosis is confirmed serologically (with an increase in antibody titers to the Lassa virus by 4 times or more). The setting of the complement fixation reaction is retrospective.

Drug treatment

Antiviral treatment is carried out by intravenous administration of ribavirin for 10 days (the initial dose of the drug is 2 g, then 1 g is administered every 6 hours for 4 days and 0.5 g every 8 hours for the next 6 days). In the early stages of the disease, convalescent plasma is used in a number of endemic regions.

Pathogenetic treatment is aimed at combating shock, hemorrhagic syndrome, cardiac and DN, as well as detoxification measures and infusion rehydration with saline solutions. Antibiotics are used for bacterial complications.__

Marburg hemorrhagic fever

Marburg hemorrhagic fever is an acute zoonotic highly lethal viral disease manifested by intoxication and severe symptoms of universal capillary toxicosis.

Etiology

Pathogen - Marburgvirus sort of Marburgvirus families Filoviridae.

Epidemiology

The reservoir of the Marburg virus has not been reliably established at this time.

The source of the pathogen is monkeys, in particular African monkeys Cercopithecus aethiops. Mechanisms of pathogen transmission: aerosol, contact, artificial. Routes of transmission: airborne droplets, contact, injection. The virus is contained in the blood, nasopharyngeal mucus, urine and semen (up to 3 months). Infection of humans occurs through direct contact with the blood and organs of monkeys, also through damaged skin (through injections, cuts), and when the virus enters the conjunctiva. A sick person is contagious to others.

Human susceptibility to Marburg virus is high. Post-infectious immunity is long-lasting. There is no information about recurrent diseases. The entrance gate is damaged skin, mucous membranes of the oral cavity and eyes. Primary replication of the virus occurs in cells of the monocyte-macrophage lineage. Then viremia develops, accompanied by suppression of the functions of the immune system and generalized microcirculation disorders, which leads to the occurrence of disseminated intravascular coagulation syndrome and multiple organ lesions. Foci of necrosis and hemorrhage are found in the lungs, myocardium, kidneys, liver, spleen, adrenal glands and other organs.

Clinical picture

Incubation period 3–16 days.

Main symptoms and dynamics of their development

The onset of the disease is acute: high fever for 2 weeks, severe intoxication, headache, myalgia, pain in the lumbosacral region.

On examination, conjunctivitis, enanthema, vesicular-erosive changes in the oral mucosa, and bradycardia are revealed. The muscle tone is increased, their palpation is painful. From the 3rd–4th day of the disease, vomiting and watery diarrhea occur, leading to rapid dehydration of the body.

On the 5th–6th day, a maculopapular rash may appear, followed by peeling of the skin. From 6–7 days, hemorrhagic manifestations are detected in the form of skin hemorrhages, nasal, gastrointestinal and other bleeding, as well as signs of hepatitis, myocarditis, and kidney damage. Damage to the central nervous system is characterized by adynamia, lethargy and meningism. At the end of the first week, signs of ITS and dehydration are revealed. The deterioration of the patients' condition occurs on the 8–10th day and on the 15–17th day of the disease (sometimes ending in death).

During the period of convalescence, which lasts 3–4 weeks, prolonged diarrhea, severe asthenia, mental disorders and baldness may occur.

Specific laboratory diagnostics are carried out using the same virological and serological methods (virus culture isolation, PCR, RNIF, ELISA, RN, RSK, etc.) as for Ebola fever. In the deceased, the virus is detected by electron microscopy or using RNIF. All studies are carried out in a laboratory with the maximum level of protection.

Drug treatment

Etiotropic treatment

Not developed.

Pathogenetic treatment

Has basic meaning. Aimed at combating dehydration, ITS, hemorrhagic syndrome. There is evidence of the effectiveness of convalescent serum, plasmapheresis and large doses of interferon.

West Nile fever

WNV (West Nile encephalitis) is an acute viral zoonotic natural focal disease with a transmissible mechanism of pathogen transmission.

It is characterized by an acute onset, pronounced feverish-intoxication syndrome and damage to the central nervous system.

The WNV virus belongs to the genus Flavivirus families Flaviviridae. The genome is represented by single-stranded RNA.

Epidemiology

The reservoir of the virus in nature is birds of the aquatic complex, the carrier is mosquitoes, primarily ornithophilous mosquitoes of the genus Culex. Between them, the virus circulates in nature; they determine the possible distribution area of ​​WNV - from the equatorial zone to regions with a temperate climate.

Pathogenesis

The pathogenesis of WNV has been little studied. It is assumed that the virus spreads hematogenously, causing damage to the vascular endothelium and microcirculatory

disorders, in some cases - the development of thrombohemorrhagic syndrome.

It was established that viremia is short-term and not intense. The leading factor in the pathogenesis of the disease is damage to the membranes and substance of the brain, leading to the development of meningeal and cerebral syndromes and focal symptoms. Death occurs, as a rule, on the 7th–28th day of illness due to disruption of vital functions due to edema-swelling of the brain substance with dislocation of stem structures, necrosis of neurocytes, and hemorrhages in the brainstem.

Clinical picture

The incubation period lasts from 2 days to 3 weeks, more often 3–8 days.

The disease begins acutely with an increase in body temperature to 38–40 ° C, and sometimes higher within several hours. An increase in temperature is accompanied by severe chills, intense headache, pain in the eyeballs, sometimes vomiting, pain in the muscles, lower back, joints, and severe general weakness.

Intoxication syndrome is expressed even in cases that occur with short-term fever, and after normalization of temperature, asthenia persists for a long time. The most characteristic symptoms of WNV caused by “old” strains of the virus, in addition to those listed, are scleritis, conjunctivitis, pharyngitis, polyadenopathy, rash, hepatolienal syndrome. Dyspeptic disorders (enteritis without pain) are common. Damage to the central nervous system in the form of meningitis and encephalitis is rare. In general, the course of the disease is benign.

Material for examination by PCR method (plasma and/or serum, CSF) must be collected using only disposable tubes and medical instruments in compliance with aseptic rules and stored at a temperature of –70 ° C or in liquid nitrogen until the study is carried out.

Serological diagnosis of WNV is possible using the methods of RTGA, RSK, RN. Currently, ELISA is most widely used in practice, allowing the detection of antibodies to the virus of the IgM and IgG classes. Early IgM antibodies are detected in the first days of the disease, and their titers reach very high levels 1–2 weeks after the onset of the disease.

Drug therapy

The effectiveness of antiviral drugs for the treatment of WNV has not been proven, therefore syndromic therapy is recommended. To combat cerebral hypertension, adults use furosemide 20–60 mg per day to maintain normal circulating blood volume. When symptoms of cerebral edema and swelling increase, mannitol is prescribed at a dose of 0.5 g/kg body weight in a 10% solution, administered quickly over 10 minutes, followed by 20–40 mg of furosemide intravenously. In severe cases (coma, breathing problems, generalized convulsions), additional dexamethasone (Dexazone♠) is prescribed at a dose of 0.25–0.5 mg/kg per day for 2–4 days. Detoxification and compensation for fluid loss is carried out by intravenous infusions of polyionic solutions (Trisol solution♠), a polarizing mixture and colloidal solutions (10%

albumin solution, cryoplasma, rheopolyglucin♠, rheogluman♠) in a ratio of 2:1. The optimal daily volume of administered fluid, including oral and tube administration, is 3–4 liters for adults and 100 ml/kg body weight for children.

To combat hypoxia, oxygen inhalation through nasal catheters is used. Patients are transferred to mechanical ventilation for the following indications - excessive shortness of breath (RR twice or more above normal), persistent hypoxemia (PaO2 less than 70 mm Hg), hypocapnia (PaCO2 less than 25 mm Hg) or hypercapnia (PaCO2 more than 45 mm Hg), coma, generalized convulsions. Electrolyte disturbances and blood osmolarity are corrected.

Marburg fever is an acute infectious viral disease characterized by severe capillary damage, intoxication, multiple organ damage, and caused by an RNA virus from the Filoviridae family. It was the symptoms of this disease that caused the fever to be called hemorrhagic - it is accompanied by high fever, hemorrhages on the skin and bleeding, intense intoxication, vomiting, damage to the heart, kidneys, testicles, central nervous system and liver.

Marburg hemorrhagic fever (HMF) is identified by infectious disease specialists as a particularly dangerous natural focal infection. This viral disease is rightly called quarantine, as it can cause large-scale epidemics and lead to a large number of deaths (from 25 to 85%). The Marburg virus is detected in the southern and equatorial parts of the African continent: the distribution area of ​​this infection includes the following countries:

• Guinea,
• Sudan,
• Zaire,
• Gabon,
• Kenya,
• Liberia,

The first outbreak of the infection discussed in this article was registered in 1967 in the German cities of Marburg and Frankfurt am Main, into which infected African green monkeys were introduced. This geographical fact predetermined its name. Also in the medical literature you can sometimes find other synonymous names:

• Maridi hemorrhagic fever;
• Marburg's disease;
• disease of green monkeys.

Outbreaks of FFM have been observed in Uganda, Kenya, South Africa, Angola, Congo, Sudan and Serbia. And the largest epidemics of this dangerous disease occurred in Angola (in 2005, 329 out of 374 patients died) and Congo (in 1998-2000, 128 out of 154 people infected died). Such high mortality rates (88 and 83%) indicate the high urgency of the need to find solutions to many problems associated with the development of methods for treating and preventing this deadly infection.

An artistic depiction of an outbreak of a similar hemorrhagic fever is presented in the famous film “Outbreak” (USA, 1995).

Reasons

The source of the virus is green monkeys Cerсopithecus aethiops, which live in Africa.

The development of Marburg fever is provoked by a filovirus from the family Filoviridae and the genus Lissavirus. The composition of this virus includes RNA and lipoprotein, and its virion, represented by 7 proteins, makes it very similar to the Ebola virus. These two microorganisms differ in their antigenic structures.

Marburg virus is characterized by polymorphism, since its shape can be rounded or helical, and its length varies from 665 to 1200 nm. It is moderately stable in the external environment, but is resistant to high temperatures (when heated to 60 ° C it remains viable for half an hour). When exposed to UV rays, the virus persists for 2 minutes; in addition, it is sensitive to a number of disinfectants:

• chloroform;
• acetone;
• ethyl and methyl alcohol;
• ether;
• formaldehyde.

The Marburg virus, like the Ebola virus, is classified as pathogenicity group I, since they can pose a significant epidemiological danger to the public and infected people. The sources of this virus are:

• green monkeys Cerсopithecus aethiops, living in Africa;
• bats Rousettus aegypti living in natural caves or mines.

These representatives of the fauna are able to tolerate the disease inapparently (that is, without showing symptoms). However, they can infect a person who has been in contact with them (for example, someone who has been to a cave or mine on an excursion). Animals imported from Africa can also serve as reservoirs of infection.

Once infected, the patient becomes infectious to other people. It releases the virus in biological fluids:

• discharge from the nose and throat;
• blood;
• urine.

With GLM, the infected person becomes dangerous to others from the first hours of the appearance of signs of the disease, and he remains dangerous for 3 weeks. According to some data, the Marburg virus can persist in the blood of a person who has been ill for about 2 months.

The mechanism of infection for this fever is the same as for Ebola fever. The most common way of spreading infection is through household contact.

• After contact with the skin or mucous membranes, the RNA virus enters the body through microtraumas and microcracks. Infection can occur through contact with urine, blood or nasopharyngeal secretions. Due to various reasons, they can fall on various objects, which then become a source of danger.
• There are known cases where infection occurred among medical personnel caring for patients with GLM.
• In addition, the airborne route of infection cannot be ruled out - after all, after sneezing or coughing, droplets of infected secretions from the nose and throat can also fall on the skin and mucous membranes, which are the entrance gates for infection.

In the literature you can find descriptions of other, more rare, mechanisms of transmission of the Marburg virus:

• reuse of disposable syringes or needles;
• improper disinfection and sterilization of reusable medical instruments;
• unprotected sexual intercourse.

Seasonality is not typical for GLM. After recovery, the patient develops long-term immunity, and so far no cases of re-infection have been described.

The entry points for the virus are microdamages on the skin and the mucous membranes of the nasopharynx and eyes. After entering the body, the GLM pathogen disseminates (that is, spreads) to organs (liver, adrenal glands, bone marrow, kidneys, spleen, heart, lungs, testicles, etc.) and tissues. There it multiplies, causes cell damage and the appearance of foci of hemorrhage and necrosis (so-called multiple organ lesions). In addition, massive viremia provokes:

• immune suppression;
• development of capillary toxicosis;
• microcirculation disturbance;
• the occurrence of DIC syndrome.

Symptoms

From the first days, the patient develops a measles-like rash on the skin.

After the virus is introduced into the body, the first signs of GLM appear in the infected person within 2-21 days. The onset of this fever is always acute:

• Initially, the patient's temperature rises to high levels (39-40 °C).
• There are manifestations of intoxication syndrome, chills, feelings of weakness and severe weakness.
• He complains of pain in muscles and joints.

From the first days of infection, the patient exhibits symptoms and exanthemas (measles-like rash), and erosions occur on the oral mucosa. After 3-4 days the following appear:

• cramping nature;
• watery diarrhea;
• vomit.

These signs of damage to the digestive tract cause the development of dehydration, which worsens the general condition of the patient to an even greater extent. Diarrhea with GLM is observed in approximately 83% of infected people and lasts for 7 days, and vomiting is less common, detected in 68% of patients and lasts 4-5 days.

After 5-6 days, the patient develops a maculopapular rash, which in some clinical cases is accompanied by a sensation and subsequent peeling of the skin. It is usually localized on the face, torso, arms and neck. In some infected people, vesicles (bubbles) are present against the background of maculopapular rashes (spots).

After this, Marburg fever takes a hemorrhagic course. The patient experiences the following symptoms:

• hemorrhages on the skin and conjunctiva;
• the occurrence of bleeding: from the gums.

By approximately the 8th day of GLM, patients show signs of multiple organ damage to the tissues of the heart muscle, kidneys, brain and liver. Due to damage to the central nervous system, the patient experiences the following symptoms:

• lethargy,
• convulsions,
• fainting,
• adynamia.

Intoxication, dehydration and hemorrhagic manifestations reach their peak in the second week of Marburg fever. In severe cases, it is during these periods that patients may die due to the following conditions:

• DIC syndrome;
• hypovolemic shock;
• cerebral edema;

When diagnosing those infected with the Marburg virus, a detailed clinical blood test reveals:

• basophilic granularity of erythrocytes;
• thrombocytopenia;
• leukopenia;
• anisocytosis;
• poikilocytosis.

When examining the cerebrospinal fluid of patients with symptoms of central nervous system damage, no changes are detected.

Recovery from Marburg fever is always long. It usually takes up to 21-30 days. During this period, infected people may experience:

• baldness;
• headaches;
• asthenization;
• myalgia;
• episodic abdominal pain;
• appetite disorders;
• long-term mental disorders.

Later, the person who has recovered from the disease may develop the following residual effects of GLM:

• uveitis;
• orchitis;
• testicular tissue atrophy;
• myelitis;
• mental disorders;
• changes in intellectual abilities.

The death rates of patients with this hemorrhagic fever are very high - 25-88%. Typically, patients die on days 8-17 from complications caused by hemorrhagic manifestations.

Diagnostics

When making a diagnosis of Marburg fever, the doctor is guided by data on the epidemiological situation and the results of the examination of the patient. Laboratory tests are always performed to confirm the final diagnosis.

• When collecting an anamnesis, the doctor always asks questions about the facts of being in natural and geographical foci of this viral infection and contact with patients with GLM.
• When assessing blood tests (and), the specialist pays attention to the presence of a reduced level of platelets and leukocytes, an increase in indicators.
• To final confirm the diagnosis, serological tests (ELISA, RIF, RN, OT-, RSK) are performed. They are complemented by electron microscopic and molecular biological techniques. Testing of such materials is carried out only in specialized laboratories that can ensure maximum safety.

GLM is always accompanied by damage to internal organs. To assess their condition, the patient is prescribed the following studies:

• Ultrasound of the abdominal organs and testicles;
• coagulogram;
• CBS (analysis of the acid-base state of the blood).

Diagnosis of the patient is supplemented by consultations:

• neurologist;
• hematologist;
• cardiologist;
• gastroenterologist;
• ophthalmologist;
• nephrologist.

To eliminate errors, differentiation of infection with other hemorrhagic fevers is carried out:

• Omsk,
• yellow,
• Argentinean,
• Lasa,

Treatment

So far, scientists have not been able to create drugs that would provide etiotropic treatment for Marburg fever. To alleviate the condition of patients, means for symptomatic and pathogenetic therapy are used.

All patients suspected of having this infection must be hospitalized in a specialized hospital, where they can be isolated in separate ward rooms. When caring for such patients, staff must comply with the rules of increased sanitary and epidemiological control to ensure the safety of others:

• an enhanced disinfection regime is being organized;
• special protective equipment is used for medical workers (anti-plague suit of the first type or its modern modifications);
• All manipulations with patients are carried out in compliance with special safety.

The treatment plan includes detoxification measures and measures are taken to rehydrate the body. Also, platelet transfusions are performed for patients suffering from hemorrhagic syndrome. If the patient develops complications caused by a bacterial infection, then antibacterial drugs are added to the treatment plan.

There is evidence in the medical literature that GLM is effective in:

• use of interferons;
• intravenous administration of plasma from recovered patients;
• the appointment of plasmapheresis.

The patient can be discharged from the hospital only after clinical recovery, which is confirmed by a three-fold result of a virological analysis. This measure can be taken no earlier than 21 days after the first symptoms of infection appear.

Forecast

There is evidence that the condition of a patient with Marburg fever can be alleviated by plasmapheresis.

Marburg fever is always dangerous and poses a threat to the population in places of outbreak of infection. The prognosis of this disease is serious, since the virus can lead to the development of complications that threaten:

• disability of the patient;
• fatal (mortality rates are extremely high and range from 25-85%).

That is why special precautions are always taken when detecting cases of GLM. To do this, the public is notified about the occurrence of infection and the need to comply with the rules of its nonspecific prevention. Treatment of infected people should be carried out only in specialized hospitals with isolation boxes.

Prevention

Unfortunately, scientists have not yet been able to develop specific preventive measures and there is no vaccine against Marburg fever.

To prevent the spread of infection in areas of GLM outbreaks, the following preventive measures should be taken:

1. If infected people are identified, the territory must be quarantined: exit and entry of the population, import or export of animals is prohibited.
2. Everyone who takes part in the fight against this viral disease is required to wear special suits that protect against especially dangerous infections, a face shield, a mask, goggles and gloves.
3. Implementation of isolation of patients in infectious disease wards and special measures when caring for them (thorough disinfection and proper disposal of all objects with which they came into contact).
4. Active identification of infected people among the population and persons who were in contact with them. Those infected should be sent to a hospital, and those who have been in contact should receive immunoglobulin (preferably as early as possible) and be under quarantine observation for 21 days. During quarantine, such individuals should have their temperature taken and undergo a medical examination to identify symptoms of DMF.
5. Cremation of deceased patients or burial only after proper disinfection of the remains.
6. Constant information work with the population and tourists located in the quarantine zone. Everyone should be aware of the first signs of the disease and the need to immediately consult a doctor.
7. Identification of attempts to hide sick people in families.
8. The population is provided with information about preventive measures and the need to subject milk, meat or dishes made from animal blood to sufficient heat treatment.
9. Treatment in the lesions is carried out using a phenol solution (2%), to which 0.5% sodium bicarbonate is added in a ratio of 1:500, or an iodoform solution of 450 g of active iodine with the addition of 0.2% sodium nitrate.
10. When working in areas where bats gather, personal protective equipment (masks, gloves, protective clothing) must be used.

In addition to intensive preventive work, measures are necessarily taken at the source of infection to prevent the import of the Marburg virus from Africa to other continents. To achieve this, travelers from Southern and Central Africa are monitored, the risk of infection is determined, and if concerns arise, quarantine sanctions are imposed for 21 days.

Marburg hemorrhagic fever is an acute zoonotic highly lethal viral disease manifested by intoxication and severe symptoms of universal capillary toxicosis. Synonyms: cercopithecus hemorrhagic fever, green monkey disease, Marburg virus disease, Maridi hemorrhagic fever.

ICD-10 code

A98.3. Disease caused by Marburg virus.

Epidemiology of Marburg hemorrhagic fever

The reservoir of the Marburg virus has not been reliably established at this time. The source of the pathogen is monkeys, in particular African monkeys Cercopithecus aethiops. Mechanisms of pathogen transmission: aerosol, contact, artificial. Routes of transmission: airborne droplets, contact, injection. The virus is contained in the blood, nasopharyngeal mucus, urine and semen (up to 3 months). Infection of humans occurs through direct contact with the blood and organs of monkeys, also through damaged skin (through injections, cuts), and when the virus enters the conjunctiva. A sick person is contagious to others. A case of sexual transmission of the pathogen has been described.

Human susceptibility to Marburg virus is high. Post-infectious immunity is long-lasting. There is no information about recurrent illnesses.

The distribution area of ​​the virus is the central and western territories of Equatorial Africa, as well as the south of the continent (Central African Republic, Gabon, Sudan, Zaire, Liberia, Kenya, Rhodesia, Guinea, South Africa). Seasonality and frequency of outbreaks have not been identified.

What causes Marburg hemorrhagic fever?

Marburg hemorrhagic fever is caused by Marburgvirus of the Marburgvirus genus of the Filoviridae family. Viral particles are polymorphic (thread-like, spiral or round in shape) with an average length of 790 nm and a diameter of 80 nm. Contains negative single-stranded RNA and lipoprotein. The virion contains 7 proteins. The protein composition of the Marburg virus is close to its related Ebola filovirus, but has some differences. It is believed that strain-specific antigens are concentrated in the region of the Gp protein, and the group-specific antigen is concentrated in the region of the Np protein. No hemagglutinins or hemolysins were detected. The virus is isolated and passaged in vitro in continuous cultures of green monkey kidney cells (Vero) and in vivo in guinea pigs. Replication occurs in the cytoplasm of affected cells. The virus has average resistance to environmental factors.

Pathogenesis of Marburg hemorrhagic fever

The entrance gates of Marburg hemorrhagic fever are damaged skin, mucous membranes of the mouth and eyes. Primary replication of the virus occurs in cells of the monocyte-macrophage lineage. Then viremia develops, accompanied by suppression of the functions of the immune system and generalized microcirculation disorders, which leads to the occurrence of disseminated intravascular coagulation syndrome and multiple organ lesions. Foci of necrosis and hemorrhage are found in the lungs, myocardium, kidneys, liver, spleen, adrenal glands and other organs.

Symptoms of Marburg hemorrhagic fever

The incubation period of Marburg hemorrhagic fever is 3-16 days.

The onset of the disease is acute, patients report symptoms of Marburg hemorrhagic fever: high fever for 2 weeks, severe intoxication, headache, myalgia, pain in the lumbosacral region. On examination, conjunctivitis, enanthema, vesicular-erosive changes in the oral mucosa, and bradycardia are revealed. The muscle tone is increased, their palpation is painful. From the 3rd-4th day of the disease, vomiting and watery diarrhea occur, leading to rapid dehydration of the body. On the 5th-6th day, a maculopapular rash may appear, followed by peeling of the skin. From 6-7 days, hemorrhagic manifestations are detected in the form of skin hemorrhages, nasal, gastrointestinal and other bleeding, as well as signs of hepatitis, myocarditis, and kidney damage. Damage to the central nervous system is characterized by adynamia, lethargy and meningism. At the end of the first week, signs of infectious-toxic shock and dehydration are revealed. The deterioration of the patients' condition occurs on the 8-10th day and on the 15-17th day of the disease (sometimes ending in death).

During the period of convalescence, which lasts 3-4 weeks, prolonged diarrhea, severe asthenia, mental disorders and baldness may occur.

Mortality and causes of death

On average 25%, but can reach 50%. Causes of death: pulmonary and cerebral edema, hypovolemic shock, acute renal failure, development of disseminated intravascular coagulation syndrome.

Diagnosis of Marburg hemorrhagic fever

Specific and nonspecific laboratory diagnosis of Marburg hemorrhagic fever

Specific laboratory diagnosis of Marburg hemorrhagic fever is carried out using the same virological and serological methods (virus culture isolation, PCR, RNIF, ELISA, RN, RSK, etc.). as with Ebola fever. In the deceased, the virus is detected by electron microscopy or using RNIF. All studies are carried out in a laboratory with the maximum level of protection.

Nonspecific laboratory diagnosis of Marburg hemorrhagic fever includes a general blood test (detect anemia, anisocytosis, poikilocytosis, basophilic granularity of erythrocytes, leukopenia, shift of the neutrophil formula to the left, atypical lymphocytes, thrombocytopenia); biochemical blood test (increased activity of transferases, amylase, azotemia); determination of the coagulogram (hypocoagulation is pronounced) and the acid-base state of the blood (signs of decompensated metabolic acidosis are detected); general urinalysis (characterized by proteinuria).

Instrumental diagnosis of Marburg hemorrhagic fever

Chest X-ray, ECG, ultrasound.

Differential diagnosis of Marburg hemorrhagic fever

Marburg fever is differentiated from the same diseases as Ebola fever (other hemorrhagic fevers, typhoid diseases, malaria, septicemia, measles, meningococcal infectious disease).

Indications for consultation with other specialists

When carrying out differential diagnosis with diseases that occur with a similar clinical picture or aggravate the course of hemorrhagic fever, consultations with relevant specialists are necessary: ​​gastroenterologist, nephrologist, neurologist, hematologist.

Indications for hospitalization

Patients with Marburg fever are subject to mandatory immediate hospitalization and strict isolation in a separate box.

Treatment of Marburg hemorrhagic fever

Mode, Diet

The patient needs strict bed rest and round-the-clock medical supervision.

The diet corresponds to table No. 4 according to Pevzner without limiting the amount of proteins and table salt (NaCl).

Etiotropic treatment of Marburg hemorrhagic fever

Etiotropic treatment of Marburg hemorrhagic fever has not been developed.

Pathogenetic treatment of Marburg hemorrhagic fever

Petogenetic treatment of Marburg hemorrhagic fever is of primary importance. Aimed at combating dehydration, infectious-toxic shock, hemorrhagic syndrome. There is evidence of the effectiveness of convalescent serum, plasmapheresis and large doses of interferon.

Approximate periods of incapacity for work

Taking into account the severity of the disease, convalescents are considered disabled for several months after discharge from the hospital.

(synonyms: Marburg fever, Maridi hemorrhagic fever; Marburg disease - English) is an acute viral disease characterized by severe course, high mortality, hemorrhagic syndrome, damage to the liver, gastrointestinal tract and central nervous system.
The causative agent of Marburg disease

The Marburg and Ebola viruses are similar in their morphology, but differ in their antigenic structure. Polymorphism is characteristic; virions can be worm-shaped, spiral-shaped and round in shape. Their length ranges from 665 to 1200 nm, cross-sectional diameter is 70-80 nm. They differ in ultrastructure and antigenic composition from all known viruses. Viral particles contain RNA, lipoprotein; the presence of hemagglutinins and hemolysins was not detected. Antigenic activity is associated with viral particles; the existence of a soluble antigen has not been proven. Viruses are isolated and passaged in guinea pigs and in a culture of continuous green monkey kidney cells (Vero). When passaged in tissue cultures, the virus has an incomplete cytopathic effect or does not cause it at all. Belongs to the family Filoviridae, genus Lyssavirus.

The first outbreaks of the disease occurred in 1967 simultaneously in the cities. Marburg and Frankfurt am Main, one patient was observed at this time in Yugoslavia. The source of infection was mainly the tissues of African green monkeys (25 patients), there were also secondary diseases (6 patients) - in two doctors, one nurse, a mortuary worker and the wife of a veterinarian. Of the 25 initially infected patients, 7 people died. Subsequently, similar diseases were observed in Sudan (near the village of Maridi, the disease was called Maridi fever), in Kenya, South Africa. The source of infection and reservoir of the virus in nature during all these outbreaks were African green monkeys (Ceropithecus aethiops), in which infection can occur inapparently. The participation of other animals in natural foci of infection, as well as the routes of transmission of infection to monkeys, have not yet been studied.

A sick person poses a danger to others. The virus is released through nasopharyngeal contents, urine, and the blood of patients is also contagious. Infection of people can occur through airborne droplets, when the virus gets on the conjunctiva, as well as on the skin (accidental needle pricks or cuts), the possibility of sexual transmission of the infection cannot be ruled out (the virus was found in seminal fluid). The virus can persist in the body of a recovered person for up to 3 months.
Pathogenesis of Marburg disease

The gates of infection are damaged skin and mucous membranes (oral cavity, eyes). Virus dissemination is characteristic. Its reproduction can occur in various organs and tissues (liver, spleen, lungs, bone marrow, testicles, etc.). The virus is detected in blood and semen for a long time (up to 12 weeks). Pathohistological changes are observed in the liver (obesity of liver cells, necrobiosis of individual cells, cellular infiltration), kidneys (damage to the epithelium of the renal tubules), spleen, myocardium, and lungs. Multiple small hemorrhages in various organs (brain, etc.).
Symptoms of Marburg Fever

The incubation period is 2-16 days. The clinical symptoms, severity and outcome of diseases described as Marburg fever and Maridi hemorrhagic fever are no different. There is no prodromal period. The disease begins acutely with a rapid increase in body temperature to a high level, often with chills. From the first days of the illness, signs of general intoxication are noted (headache, fatigue, muscle and joint pain), after a few days lesions of the gastrointestinal tract and hemorrhagic syndrome appear; Dehydration develops and consciousness is impaired.

In the initial period, the patient complains of a diffuse headache or more pronounced in the frontal region, stabbing chest pain, aggravated by breathing, chest pain, and sometimes a dry cough. There is a feeling of dryness and pain in the throat. There is hyperemia of the mucous membrane of the pharynx, the tip and edges of the tongue are red; vesicles appear on the hard and soft palate and tongue, and when opened, surface erosions are formed; unlike Lassa fever, no pronounced necrosis is observed. The tone of the muscles, especially the back, neck, and masticatory muscles, is increased, and their palpation is painful. From the 3-4th day of illness, cramping pain in the abdomen begins. The stool is loose, watery, and half of the patients have blood in the stool (sometimes in clots) or signs of gastrointestinal bleeding (melena). Some patients experience vomiting with an admixture of bile and blood in the vomit. Diarrhea is observed in almost all patients (83%), lasting about a week; vomiting occurs less frequently (68%) and lasts 4-5 days.

In half of the patients, on the 4-5th day of illness, a rash (sometimes morbilliform) appears on the body; in some patients, vesicular elements may be noted against the background of a maculopapular rash. The rash spreads to the upper limbs, neck, face. Sometimes itchy skin bothers me. With the development of hemorrhagic syndrome, hemorrhages appear in the skin (in 62% of patients), in the conjunctiva, and the oral mucosa. At this time, nasal, uterine, and gastrointestinal bleeding appears. At the end of the 1st, sometimes at the 2nd week, signs of toxicosis reach their maximum severity. Symptoms of dehydration and infectious-toxic shock appear. Sometimes convulsions and loss of consciousness are observed. During this period, patients often die.

When examining blood, leukopenia, thrombocytopenia, anisocytosis, poikilocytosis, and basophilic granularity of erythrocytes are noted. Cerebrospinal fluid, even in patients with signs of irritation of the meninges, remains unchanged. The recovery period lasts for 3-4 weeks. At this time, baldness, periodic abdominal pain, loss of appetite and long-term mental disorders are noted. Late complications include transverse myelitis and uveitis.

Complications
The development of early encephalitis, as well as myelitis, orchitis, mental disorders, and decreased intelligence is possible. In severe cases, the causes of death can be infectious-toxic shock, hypovolemic shock, pulmonary and cerebral edema.

The mortality rate reaches 30% or more, death usually occurs between 8-17 days of illness from hemorrhagic manifestations.
Diagnosis of Marburg disease

Specific laboratory research methods can detect the virus or antibodies to it. Work with virus-containing material is carried out in compliance with preventive measures only in specially equipped laboratories. When taking material for laboratory research, follow the packaging and shipping rules recommended for especially dangerous infections (place in metal containers, send to laboratories by express). Antibodies in the blood serum of patients are determined using the immunofluorescence method.
Treatment of Marburg Fever

There are no means of etiotropic therapy. Pathogenetic and symptomatic therapy is carried out, convalescent plasma is administered. The use of interferon and their inducers is ineffective.
Prevention of Marburg Fever

Identification of patients, their isolation, quarantine measures. A heterogeneous (equine) serum immunoglobulin has been developed for immunoprophylaxis of high-risk populations.