Argentine hemorrhagic fever is a natural focal zoonosis from the group of South American hemorrhagic fevers caused by the RNA-containing Junin virus. The leading clinical manifestations are hemorrhagic syndrome with bleeding of various localization, severe intoxication. Diagnosis is based on the detection of the pathogen itself and specific markers in the blood serum. Etiotropic treatment consists in the introduction of immune plasma. The appointment of ribavirin shows good results. Taking into account the developed disorders, symptomatic therapy is prescribed.
A96.0 Hemorrhagic fever Junin
The focus of hemorrhagic Junin fever is the humid ecosystem of the Pampas of Argentina. Outbreaks occur annually from February to June with a peak in May. Men are most often ill, the infection is more common among the rural population. Most of the cases are people of working age. On average, up to 4,000 people are affected annually, and during outbreaks, the number of infected can reach 20,000. About 10% of the local population are seropositive without a history of infection. Due to the active immunization of the inhabitants of this region, it has recently been possible to control the incidence with a decrease in the frequency of episodes with a severe course. Since this vaccination is not included in the list of mandatory when entering Argentina, cases of infection of tourists have become more frequent.
The causative agent of the infection is an RNA–containing Junin virus from the genus Arenavirus of the Arenaviridae family. The virus dies under the influence of detergents, UVI, but remains in a freeze-dried state for a long time. The reservoir, as well as the source of infection, are hamster-like rodents, as well as a sick person. Between rodents, the pathogen is transmitted transmissively with the bites of gamas ticks. Penetrating into the blood, the virus in hamsters causes a latent course of the disease and asymptomatic viremia. The pathogen from the body of rodents is excreted in the urine.
The infectious agent enters the human body by airborne dust when inhaling dust contaminated with rodents, as well as when implementing a fecal-oral mechanism with infected food and water, during sexual contact and through damaged skin. When a tick is bitten by a virus, the disease does not develop in a person. Cases of intra-laboratory infection by aspiration with the development of manifest forms or asymptomatic course are described annually. After the disease, a stable immunity is formed.
The mechanism of development of Argentine hemorrhagic fever is not fully understood. Getting into the alveolar macrophages and bronchopulmonary lymph nodes, the Junin virus spreads hematogenically and lymphogenically throughout the body. The pathogen is fixed in the cells of the reticuloendothelial system, damaging them, thereby contributing to leukocytopenia and thrombocytopenia. Lymphadenopathy develops, atrophy and necrosis are observed in the lymphoid follicles. Damage to the capillary wall leads to hemorrhagic syndrome, hypovolemic shock. Damage to the vessels of internal organs contributes to the disruption of their function. Depending on the viral load, both asymptomatic forms with an increase in antibody titer and severe conditions may develop.
Symptoms of argentine hemorrhagic fever
The incubation period after infection is about 7-14 days. The disease begins gradually, non-specific symptoms appear: fever, weakness, malaise, headache, arthralgia, myalgia. In a short period of time, the body temperature increases to febrile numbers, there is an enanthema on the conjunctiva, the oral mucosa. Objectively, redness of the face, neck, injection of sclera vessels, lymphadenopathy is determined, hemorrhagic rash can rarely appear. The first stage of the disease is characterized by bradycardia, myocarditis often develops.
The duration of the fever period is about 10 days. Further, the symptoms of hemorrhagic syndrome manifest themselves: bleeding of the gums increases, nosebleeds, hematuria, melena are noted. Blood pressure drops to 60 mm Hg, hemorrhagic shock develops with massive bleeding. There may be symptoms of central nervous system damage with an increase in neurological deficit (agitation, stupor, signs of encephalitis). The period of reconvalescence ranges from 2 weeks to several months.
The most common complication is hemorrhagic shock. With severe shock, the development of multiple organ disorders (acute renal, cardiac, respiratory failure) is likely. In addition, CNS lesions of various types with the addition of neurological syndromes (encephalopathy, encephalitis) are possible. In vaccinated patients, transient alopecia sometimes appears after an infection. Quite often, bronchopneumonia occurs against the background of leukopenia and damage to the capillary wall. The most common cause of death is pulmonary edema. Due to the introduction of vaccination, severe forms of the disease are becoming less common.
If hemorrhagic fever is suspected, an infectious disease specialist should be consulted, followed by hospitalization of the patient in the intensive care unit of an infectious disease hospital. During the physical examination, there are no specific symptoms for this viral infection. Attention is drawn to the general intoxication syndrome, redness, swelling of the neck, face, possibly the presence of petechial rash, lymphadenopathy. The appearance of conjunctivitis, enanthema on the oral mucosa is characteristic. The following clinical and laboratory methods are used in diagnostics:
- General and biochemical study of the material. Due to damage to the cells of the reticuloendothelial system, the presence of platelet and leukopenia is noted in the blood test. Due to the lesion of the vascular wall and the extravasation of the liquid part of the blood, signs of blood thickening are observed. In the general analysis of urine – proteinuria. The daily loss of protein in the urine can reach 10 g. When multiple organ failure occurs in the blood, the corresponding markers (AlAT, AsAT, urea, creatinine) increase.
- Identification of infectious agents. To detect specific antibodies, blood is taken 2 weeks after the onset of the disease. This method is rather retrospective. Complement binding reaction, indirect immunofluorescence reaction, hemagglutination inhibition reaction are used. To detect the virus, pharyngeal flushes, urine are examined; sampling is carried out up to 7 days from the onset of the disease. The most sensitive method for detecting the pathogen in the early stages is PCR with reverse transcription.
Given the relative rarity of this nosology outside of endemic areas and the non-specificity of the initial symptoms, diagnosis can cause significant difficulties. Differentiation is carried out with other hemorrhagic fevers, in particular, with South American (Bolivian, Venezuelan, Brazilian). At the stage of intoxication in the absence of a pronounced hemorrhagic syndrome, it is necessary to exclude influenza, arbovirus infections, sepsis, and in the midst of the disease – hemorrhagic diathesis. Finding out the anamnesis of the disease, as well as comparing the clinical picture data with the results of tests, allows you to establish the correct diagnosis and prescribe appropriate treatment.
Treatment of argentine hemorrhagic fever
Treatment should be carried out in isolation of the patient under the supervision of an infectious disease specialist. When complications are added, it may be necessary to consult specialized specialists (neurologist, pulmonologist, nephrologist, cardiologist). Strict bed rest must be observed. The main method of therapy is plasma transfusion of convalescents. This method gives the best results at the initial stages of the disease (up to 8 days).
There is evidence of positive results of ribavirin treatment. This method is especially relevant in the absence of immune plasma. According to WHO recommendations, the drug is administered intravenously on the first day at a dose of 30 mg / kg once, then 15 mg / kg 4 times / day for 4 days and 7.5 mg / kg / day for 6 days. In parallel, symptomatic treatment is carried out with the correction of developed disorders (detoxification therapy, blood volume compensation, the use of cardiovascular drugs, antipyretic drugs, correction of hemostatic system disorders).
Prognosis and prevention
With a timely recognized disease and proper treatment, the prognosis is favorable. In the case of severe forms, the duration of Argentine hemorrhagic fever is about 11 days, and the mortality rate reaches 15%. Measures of non-specific prevention include the control of rodents in endemic areas through the use of toxic substances, special traps. In addition, it is necessary to use respirators for dust work. Vaccination of local residents allows you to control the course of morbidity. To date, a live attenuated vaccine is being used, experimental samples are being tested. The use of ribavirin as an emergency prophylaxis is not recommended. The exception is pregnant patients who have been in contact with the patient.