Rift Valley fever is an acute arbovirus infection. The main symptoms of the disease are lesions of the central nervous system, eyes and liver, various hemorrhagic manifestations. The disease is accompanied by severe intoxication and fever. The diagnosis is based on the methods of virus isolation from the biological substrates of the patient and the detection of antibodies to the pathogen in the patient’s blood. Treatment is pathogenetic and symptomatic, aimed at facilitating the course of pathology, correction of impaired visceral functions. Etiotropic agents have not been developed.
A92.4 Rift Valley Fever [Rift Valley]
Rift Valley fever (Rift Valley fever) is a disease with a contact, rarely transmissible transmission pathway. The first mention of nosology dates back to 1915, 15 years later the pathogen was isolated by English veterinarians Hudson and Dobney, as well as virologist Harnham. The disease has been registered in Egypt, Kenya, Saudi Arabia, South Africa, Sudan, and several other countries of the African continent. Seasonality is year-round with an increase in cases of infection of people and animals during tropical downpours. Large outbreaks of epizootics are described with a cycle of 10-15 years. There were no gender differences in the incidence rate.
The causative agent of the disease is a virus of the same name. Wild and domestic animals serve as reservoirs and sources of infection: elephants, rhinos, bats, gazelles, cows, goats, sheep, buffaloes, camels. Transmission of the virus is carried out by contact with biological material – in the process of butchering carcasses, cooking, caring for animals. Aerogenic infection is described when working with the virus in laboratories. Direct transmission from person to person has not been proven. The transmissible transmission pathway is implemented by mosquitoes, some blood-sucking flies.
The main risk factors are children’s age, living in rural areas. Farmers, veterinarians and shepherds, people working in slaughterhouses and meat processing plants are most often infected. The danger is posed by territories with extensive irrigation systems, which are breeding grounds for mosquitoes. Large outbreaks are characterized by the appearance of new secondary foci of the disease associated with the movement of livestock, passive migration of vectors. Transovarial transmission of the virus among Aedes mosquitoes has been proven.
After penetration through damaged skin and mucous membranes or a mosquito bite, the virus enters the regional lymph nodes, where it actively multiplies and accumulates. The spread of hematogenic path leads to damage to organs and tissues, there are mononuclear infiltrates, focal necrosis caused by both direct exposure to the virus and the peculiarities of the immunological response of the body. There is a link between an increase in the level of IL-8, IP-10, IL-10 and death; cytokine dysregulation is a predictor of severe course.
The pathogen shows the greatest tropism to liver tissue, renal glomeruli, epithelial cells of the renal tubules; it is for the liver and kidneys that pronounced dystrophic and necrotic transformations are characteristic. Endotheliocytes are also a viral target. Pathomorphological changes leading to thinning of the vascular wall, increased penetration of fluid and blood cells through it are caused by immunopathological processes. Pronounced vasculitis in the retinal area almost always leads to the threat of detachment and blindness.
Modern infectious disease specialists distinguish subclinical, mild, moderate and severe course of the disease. The frequency of occurrence of severe forms is no more than 1%. Rift Valley fever is also classified according to the affected organ. This infection is characterized by the involvement of the brain and its membranes, as well as the liver, eyes and hemostasis system.
- Eye shape. It occurs in 0.5-2% of patients, as an isolated condition does not cause deaths. The main symptoms are associated with a decrease in visual acuity and quality. Cases of spontaneous recovery after 10-12 weeks are described.
- Meningoencephalitic form. About 1% of patients suffer. The debut takes place no earlier than the 4th week of illness. Despite the severity of the course, the mortality rate is low. The danger is represented by residual neurological symptoms that appear 2 or more months after the acute period.
- Hemorrhagic form. Develops a few days after the onset of the disease. In the pathogenesis – hepatic necrosis, deficiency of coagulation factors, DIC syndrome. Death occurs in 50% of patients with this form, usually within 3-6 days.
The incubation period is 3-6 days. The onset of the disease is acute against the background of normal well-being. There is pronounced chills, muscle and joint pain, weakness. Eye movements are painful, photophobia is noted, redness of the face and sclera, hyperthermia of more than 39 ° C. There is a short-term decrease in body temperature to almost normal values, after 1-2 days a period of hyperpyrexia occurs again. In most cases, no other symptoms are observed, and a full recovery occurs within a week.
A severe hemorrhagic form of fever debuts after 2-4 days of illness with the occurrence of jaundice and spot hemorrhages. In the future, profuse gastrointestinal, uterine and other bleeding develops. Patients may complain of progressive decrease, blurred vision on the 7th-14th day of infection. On the 7th-30th day of the disease, brain damage may occur, accompanied by dizziness, confusion, hallucinations, severe headaches with vomiting at the height of the attack, non-relieving analgesics.
The most common complications include the consequences of pathological processes in the liver. Arbovirus can cause complete hepatonecrosis, especially in children. In adults, liver lesions lead to a deficiency of clotting factors, bleeding, and toxic encephalopathy. Vascular viral invasions aggravate the course of hemorrhagic syndrome. Vasculitis, occlusion of vessels near the macula in half of cases are the cause of macular edema and irreversible blindness. Neurological consequences of encephalitis (paralysis, paresis) can persist for life.
In modern clinical infectology, diagnosis verification is carried out on the basis of a consultation with a specialized specialist, in some cases, an ophthalmologist and other doctors. Strict compliance with the rules of transportation and examination of samples obtained from the patient is necessary – it is allowed to work with them only in the laboratory of particularly dangerous infections. The main diagnostic studies are:
- Physical examination. There are often no changes. It is possible to detect jaundice of the sclera and skin, hemorrhagic rash (petechiae, purpura, ecchymosis), neurological changes: rigidity of the occipital muscles, meningeal signs. It is required to actively identify visual disturbances, episodes of gingival and nasal bleeding.
- Examination of the fundus. Ophthalmoscopy is indicated for all patients with suspected Rift Valley fever, especially in the presence of visual impairment. With the ocular form, visual acuity is reduced, during perimetry, detection by cattle is possible. On the fundus, macular edema, hemorrhages in the vitreous, retina, signs of vasculitis are determined.
- Laboratory tests. A general clinical blood test is characterized by leukocytosis, followed by leukopenia and thrombocytopenia. There is an increase in the activity of biochemical indicators: ALT, AST, total and direct bilirubin, urea, creatinine. In the general analysis of urine – microhematuria, cylindrical. In the cerebrospinal fluid – moderate lymphocytic cytosis.
- Identification of infectious agents. Isolation of the virus in cell culture is a complex and expensive method. Isolation of the fever pathogen from the patient’s blood is performed by PCR with reverse transcription. Serological diagnostics is carried out with the help of ELISA, allows to establish a diagnosis retrospectively, is used in endemic areas during epidemiological studies.
- Instrumental techniques. Chest x-ray is prescribed during differential diagnosis. Ultrasound of the abdominal cavity, retroperitoneal space, orbits, eyeballs is recommended. To exclude vascular focal and tumor lesions, EEG, CT, MRI of the brain, departments of the visual apparatus with contrast enhancement is performed.
Differential diagnosis is carried out with hemorrhagic fevers Ebola, Lassa, Marburg, Crimea-Congo. The clinical manifestations of these infections are almost similar, etiological verification is possible only by laboratory methods. Malaria is manifested by prolonged hyperpyrexia, hepatosplenomegaly, attacks of “chills-fever-sweat”. With yellow fever, jaundice, toxic lesions of the cardiovascular and nervous systems, oliguria are noted. Typhoid fever is characterized by the presence of somnolence and typhoid status, hepatosplenomegaly, flatulence, intestinal paresis.
Patients with Rift Valley fever should be treated in a hospital. Bed rest is indicated during the period of an increase in body temperature until its normalization within 4-5 days and in case of complications. Dietary recommendations consist in a gentle diet with the exception of hard-to-digest food, alcohol. The water load should be increased in the absence of contraindications.
Etiotropic treatment has not been developed. Great importance is attached to detoxification and anti-inflammatory therapy, the use of acetylsalicylates and their analogues is not recommended. Correction of hepatic-cellular insufficiency, inflammatory changes in the substance of the brain, thrombohemorrhagic syndrome is carried out. According to the indications, infusions of thrombomass, freshly frozen plasma and albumin solution are carried out. Symptomatic agents are prescribed taking into account the emerging manifestations, existing complications.
A candidate for the role of a drug active against the Rift Valley virus is sorafenib. The drug was originally developed for the treatment of renal cell and hepatocellular carcinomas. In vitro studies have shown the effectiveness of sorafenib as an inhibitor of viral RNA synthesis, as well as as a drug that prevents the release of virions from the cell. The effect on viral replication mainly proceeds by inhibiting heat shock proteins necessary for the formation of new copies of the pathogen.
Prognosis and prevention
The prognosis for a typical course is favorable. The mortality rate, taking into account the form, ranges from 0.25% to 50%, most of the deaths occur in childhood. The duration of the disease in the absence of complications usually does not exceed 4-7 days. It is necessary to remember about the proven epidemiology of the Rift Valley virus – when bitten by mosquitoes of the genus Culex, infected with the filaria Wuchereria bancrofti, the transmission of the pathogen Rift Valley proceeds more easily. At the same time, there remains a high probability of helminth invasion and, as a consequence, the combined disease of vuchereriosis.
Killed, vector and recombinant vaccines have been developed for veterinary practice. Since the 60s of the twentieth century, inactivated virus cultures have been used for specific prevention in risk groups. Non-specific measures to prevent the disease include vector control in the form of drainage of swamps and the use of insecticides, as well as timely isolation of sick people, strict veterinary control in animal husbandry. It is necessary to avoid eating raw milk, poorly heat-treated meat, offal.