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Peter L. Ferine

Definition Epidemic relapsing fever is an acute infection characterized by repeated cycles of a rise in body temperature, which are separated from each other by asymptomatic intervals of apparent recovery. It is caused by spirochetes of the genus Borrelia and is represented by two epidemiological varieties - a disease transmitted by lice and a disease transmitted by ticks.

Etiology. Representatives of the genus Borellia are graceful, spiral-shaped, motile microorganisms with a length of 7 to 20 microns, a diameter of 0.7 microns. Unlike other spirochetes, they are easily stained with aniline dyes. They are microaerophiles, and the strains parasitizing in the body of ticks grow well on Kelly's medium. Borrelia - the causative agents of tick-borne tick-borne typhus - are antigenically more diverse than the causative agents of epidemic typhus and are more common in nature. The causative agent of epidemic typhus is B. recurrentis. The causative agents of tick-borne relapsing fever typhus are named according to ticks and their carriers. In the USA, these include B. hermsi, B. parkeri, and B. turicate.

Epidemiology. Epidemiological relapsing fever is transmitted from person to person only with a bite of lice, which suck blood infected with B. recurrentis. Spirochetes penetrate the wall of the intestine of the louse and multiply in its body. Infection occurs when the louse is crushed at the site of the bite or when combing the site of the bite. The reservoir of infection in the animal kingdom has not been established. The infection is endemic in parts of central and eastern Africa, the Peruvian Andes and China, where poverty and crowding contribute to increased breeding of lice, especially during famines and wars. In the current century, several pandemics have occurred in Africa, the Middle East and Europe, affecting 50 million people and resulting in the deaths of 5 million people. Like typhoid, the disease is currently being detected in refugee camps in Ethiopia and Sudan. Isolated cases of epidemic relapse fever have been brought into Europe and North America.

Tick-borne ticks belong to several species of the genus Ornithodorus. These long-living argas mites are prone to solitary living, they usually bite at night squirrels and other small rodents that feed on the ground. Their bites are painless and last less than an hour. A small, itchy scab may appear at the bite site in a few days. Ticks, both males and females, are usually potential carriers of infection, and females pass spirochetes to their offspring. A tick-borne fever reservoir limited to ticks and rodents may exist for decades near human housing. The transmission of infection to humans occurs if spirochete mite saliva or tissue fluid from the mite's body contaminate the bite site. In the United States, most cases occur in spring and summer, during the period of activity of ticks and rodents, most often in the western states, from Texas in the south to Colorado, Washington, Montana and Idaho in the northwest. Cases of group diseases are often associated with visits to homes massively populated by ticks by travelers from other regions of the country.

Pathogenesis and pathological changes. Having penetrated the human body, Borrelia is introduced into the bloodstream and causes spirochemia. Although spirochetes populate most organs and tissues, the pathogen is preserved and multiplies primarily in the vascular system. Fever, the first manifestation of the disease, begins 3-12 days after infection. The severity of a febrile condition and tissue damage to a certain extent correlates with the number of circulating spirochetes, the number of which in severe forms of the disease can reach more than 100 • 109 / l. Damage to endothelial borrelia and subacute disseminated intravascular coagulation with thrombocytopenia and the release of blood elements into serous membranes and skin are widespread. 3-5 days after the onset of the disease, immobilizing (opsonizing) antibodies appear, and the pathogen is quickly captured from the bloodstream by leukocyte phagocytosis, which is accompanied by a short-term rise in body temperature. The exact mechanisms causing fever and crises are not known, but in all likelihood, the endotoxin-like substances and / or non-endotoxin pyrogenic substances inherent in borrelia are involved in them. Body temperature decreases, but a small amount of spirochetes of a new antigenic variant is stored in the blood or in tissues. A new variant is formed spontaneously during genetic mutations with a frequency of one individual per 103 - 105 spirochetes and carries surface proteins different from those in the spirochetes that caused the infection, or in the previous serotype. The causative agents of this new antigenic type multiply and after a latent period of approximately 1 week, their number reaches a detectable limit, after which they cause a second attack of fever. With epidemic relapse fever, the number of relapses is less than with tick-borne fever, which is probably due to the production of antibodies to the common integral proteins that are present in each new variant.

At autopsy, microabscesses in the spleen, petechiae on the serous membranes, intracranial hemorrhages, diffuse histiocytic myocarditis, hepatitis with focal foci of necrosis are detected. Spirochetes can also cross the placenta and cause abortions or relapsing fever in newborns.

Clinical manifestation. Symptoms and signs of the disease are more pronounced with epidemic recurrent fever, and with tick-borne fever, their severity may vary depending on the type of pathogen. After an incubation period of 3 to 18 days, the disease develops sharply, suddenly and is manifested by a sharp increase in body temperature (39-40 ° C), which persists until the crisis develops. Patients have a sharp weakness with some violations of their mental status. They complain of headaches, pain in muscles and joints, weakness and loss of appetite. Nausea, vomiting, pain in the upper abdomen, and unproductive cough are often noted. The pulse is accelerated accordingly to an increase in body temperature, and with an epidemic relapse fever, a ventricular rhythm disturbance is often noted. Widening of the borders of the heart and heart failure are rare. Approximately 40% of patients develop meningism. The liver and spleen are painful on palpation and are enlarged in most patients, especially those suffering from epidemic recurrent fever. Jaundice, as a secondary complication of developing damage to the liver cells, is observed in 10–80% of patients; usually this complication occurs in the later stages of the disease and is more characteristic of the epidemic form of the disease.

Bleeding is characteristic of both types of disease. In 10-60% of patients, a petechial or bruising-like ecchymotic rash is noted. Later, with the development of hepatitis, 25% of patients experience heavy and prolonged nosebleeds. Less commonly observed hemoptysis, hematuria, conjunctival hemorrhage and retina. In the terminal stages of fatal diseases, cerebral and gastrointestinal hemorrhages can occur. Transient local neurological symptoms can develop without intracranial bleeding. Photophobia is common, and in patients with tick-borne relapsing fever, after several relapses, iritis or iridocyclitis may develop, leading to visual impairment.

3-6 days after the onset of the disease, it is resolved by the development of a crisis that begins with a short period of chills, which are accompanied by transient, but pronounced rises in body temperature, an increase in the number of heart contractions, respiratory rate and systolic blood pressure. This, in turn, is accompanied by a decrease in body temperature and peripheral vascular resistance, which leads to a state of hypotension, which lasts for several hours. During the hypotensive phase of the disease, acute heart failure and fatal cardiac arrhythmia can develop, but in most patients all physiological parameters return to normal within 24 hours, and although the patient remains severely weak, recovery occurs. An identical crisis - a reaction similar to the Jarisch-Gersheimer reaction - can develop under the influence of antibiotics. Mediators of this have not been established, but it is known that the initial stage is the phagocytosis of spirochetes opsonized or damaged by antibiotics. The period of apparent recovery with normal body temperature lasts from 5 to 7 days, after which a relapse develops with a rise in temperature. In relapse, all symptoms are less pronounced, a shorter period of time persists, and the crisis is less severe than in the first episode of the disease. While with epidemic relapsing fever, only one or two relapses are observed, with tick-borne relapsing fever during the several weeks of the disease, many relapses are noted.

Laboratory research. Mild anemia is characteristic. The number of leukocytes is usually within normal limits and only during the peak period is leukopenia observed. ESR increased. Thrombocytopenia with a platelet count of less than 150 • 109 / L and an increase in bleeding time are regularly detected. An elevated level of serum aminotransferases, bilirubin and an increase in the time of formation of prothrombin and, in part, thromboplastin are characteristic. Most patients with epidemic recurrent fever have azotemia that is not associated with extracellular fluid volume. Changes in the electrocardiogram are characterized by an increase in the QTc interval. Most patients with epidemic and 30% of patients with tick-borne relapsing fever develop agglutinins for Proteus OHC antigens.

Diagnosis is based on the detection of peripheral blood borrelia during fever attacks by examining blood smears stained by Giemsa or Wright. Repeated studies may be required. Mobile spirochetes can be detected in wet preparations of freshly obtained blood when examined in a dark field or using a phase contrast microscope. If tick-borne fever is suspected and the results of using direct methods for identifying the pathogen are negative, the patient’s blood can be injected into mice or rats and then their blood can be re-examined for the presence of spirochetes.

Differential diagnosis. In the differential diagnosis, the following acute febrile diseases must be considered: Lim disease, rat bite fever, salmonellosis, typhoid and Weil's disease. In practice, errors are rarely observed if the patient’s history of travel information is taken into account and a thorough examination of blood smears is performed.

Treatment. In the treatment with penicillin, tetracycline, erythromycin or chloramphenicol, the blood quickly releases from spirochetes. The first dose of any of these antimicrobials usually provokes a reaction similar to the Yarish-Gersheimer reaction, which develops 1-2 hours after the start of treatment. With an epidemic relapsing fever, the reaction is so severe that it can lead to a fatal outcome; with tick-borne relapsing fever, the Yarish-Gersheimer reaction is less pronounced. Treatment should be carried out in a hospital where maintenance therapy is provided and vital indicators can be correctly assessed. During the first 24 hours from the start of treatment, bed rest is necessary to prevent hypotension associated with the position of the body and the development of potentially fatal cardiac arrhythmias. In order to lower body temperature, it is advisable to take paracetamol and rub with a warm, damp sponge. Most patients have hypovolemia, and during the first 24 hours of treatment they require the introduction of 4 or more liters of isotonic solution. Vitamin K is recommended for patients with bleeding and jaundice; heparin is ineffective in controlling coagulopathy and should not be prescribed.

In epidemic relapsing fever, the drugs of choice are tetracycline, chloramphenicol or erythromycin stearate 500 mg in a single dose orally or intravenously. Children under 12 years of age should be given 1/2 dose. Slow intravenous administration of meptazinol in a dose of 100 mg while taking tetracycline reduces the severity of a reaction similar to the Yarish-Gersheimer reaction.

When tick-borne relapsing fever is recommended, the use of tetracycline hydrochloride 500 mg orally in a single dose, possibly intravenous administration of the drug. Doxycycline at a dose of 100 mg 2 times a day is also effective. For children under the age of 12, 1/2 dose is recommended. Patients with hypersensitivity to tetracycline are given erythromycin stearate or chloramphenicol 500 mg orally every 6 hours for 10 days.

Forecast. If untreated, the frequency of deaths during epidemics of epidemic recurrence of typhoid varies from 30 to 70%. Adequate treatment reduces mortality to 1% or less. Adverse reactions include severe jaundice, delusional state or coma, persistent bleeding, and marked prolongation of the QTc interval.

Along with epidemic relapsing fever, the patient may develop typhoid, malaria, and intestinal fever, which are likely to increase mortality, especially during epidemics.
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