Tsutsugamushi fever: causes, symptoms, diagnosis, treatment

Tsutsugamushi fever (synonyms: Japanese river fever (English), schichito disease (Japanese-English), Malayan rural typhus, New Guinea fever) is an acute transmissible natural focal rickettsiosis characterized by fever and other manifestations of intoxication, the development of a typical primary affect, abundant maculopapular rash, and lymphadenopathy.

Tsutsugamushi Fever: Brief Historical Facts

In China, tsutsugamushi fever has been known since the 3rd century under the name "shu-shi", which means "bite of a small red insect" (rudd mites). The scientific description of the disease was first presented by the Japanese doctor N.K. Hashimoto (1810). The causative agent of the disease - O. tsutsugamushi - was discovered by N. Hayashi in 1905-1923. In 1946, a vaccine for immunizing the population in outbreaks appeared.

Epidemiology of tsutsugamushi fever

The reservoir and sources of the pathogen are mouse-like rodents, insectivores and marsupials, as well as their ectoparasites - red-bodied ticks. Animals carry the infection in a latent form, the duration of their infectious period is unknown. Ticks retain infectiousness for life, transovarial and transphase transmission of rickettsia occurs. A sick person does not pose an epidemiological danger.

The transmission mechanism is transmissive, the carriers are the larvae of red mites, parasitizing animals and humans.

Natural susceptibility of people is high. Post-infection immunity is homologous and long-lasting, but in endemic foci there may be cases of reinfection.

Tsutsugamushi fever is found in many countries of Central, East and Southeast Asia and on the Pacific Ocean islands (India, Sri Lanka, Malaysia, Indonesia, Pakistan, Japan, South Korea, China, etc.). In Russia, natural foci of infection are known in Primorsky Krai, the Kuril Islands, Kamchatka, and Sakhalin.

In endemic areas, tsutsugamushi fever is recorded as sporadic cases and group outbreaks; mass explosive outbreaks have been described among visitors. Summer seasonality is expressed with a peak in July-August, which is explained by the biological activity of ticks at this time. People of all age and sex groups become ill (mainly those engaged in agricultural work in river valleys with shrub and grassy thickets - the biotope of red-bodied ticks).

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Causes of Tsutsugamushi Fever

Tsutsugamushi fever is caused by a small polymorphic gram-negative bacillus Orientia tsutsugamushi, which belongs to the genus Orientia ofthe Rickettsiaceae family. Unlike representatives of the genus Rickettsia, Orientia lack some components of the peptide glycan and LPS (muramic acid, glucosamine and oxidized fatty acids) in the cell wall. The pathogen is cultivated in ticks, transplantable cell cultures and the yolk sac of chicken embryos; in infected cells, it parasitizes in the cytoplasm and nucleus. It is divided into 6 serological groups and has a common antigen with Proteus OX ₁₉.

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Pathogenesis of tsutsugamushi fever

The primary affect occurs at the site of the tick bite. The pathogens enter the regional lymph nodes via the lymphatic route from the entry point, forming lymphangitis and regional lymphadenitis. After the primary accumulation of rickettsiae in the lymph nodes, the hematogenous dissemination phase develops. The proliferation of pathogens in the cytoplasm of body cells, primarily in the vascular endothelium, explains the development of vasculitis and perivasculitis, a key link in the pathogenesis of tsutsugamushi fever. Small vessels of the myocardium, lungs, and other parenchymatous organs are predominantly affected. Desquamation of endothelial cells underlies the subsequent formation of granulomas similar to typhus, but histological changes in the vessels with tsutsugamushi fever are less pronounced and do not reach the stage of thrombosis and necrosis of the vascular walls, as with typhus.

Symptoms of Tsutsugamushi Fever

The incubation period of tsutsugamushi fever lasts on average 7-12 days, with variations from 5 to 20 days. Symptoms of tsutsugamushi fever are quite similar to other infections from the group of rickettsial spotted fevers, but in different foci the clinical picture and severity of the disease vary significantly.

Primary affect does not occur in all patients. It can be detected already at the end of the incubation period as a small (up to 2 mm in diameter) compacted hyperemia spot. This is quickly followed by chills, a feeling of fatigue, severe headache, and insomnia. Myalgia and arthralgia may occur. Body temperature rises to high values. Primary affect is transformed into a vesicle, and then gradually, over many days, into an ulcer with a peripheral hyperemia zone and into a scab. Regional lymphadenitis appears at the same time. The primary affect then persists for up to 2-3 weeks.

When examining patients from the first days of the disease, the following symptoms of tsutsugamushi fever are noted: hyperemia and puffiness of the face, pronounced conjunctivitis and scleritis. Less than half of patients develop a spotted rash on the chest and abdomen on the 5th-8th day of the disease, subsequently the rash elements become maculopapular, spread to the extremities, without affecting the palms and soles. The frequent absence of primary affect and exanthema significantly complicates the diagnosis of tsutsugamushi fever.

The exanthema persists for an average of a week. During this period, severe intoxication develops, generalized lymphadenopathy forms (which distinguishes the disease from all other rickettsioses), tachycardia, muffled heart sounds, systolic murmur, and decreased blood pressure are detected. Myocarditis develops more often than with other rickettsioses. Pulmonary pathology manifests itself as signs of diffuse bronchitis, and in severe cases, interstitial pneumonia. The liver is usually not enlarged; splenomegaly develops more often. As intoxication increases, manifestations of encephalopathy increase (sleep disturbance, headache, agitation). In severe cases, delirium, stupor, convulsions, development of meningeal syndrome, and glomerulonephritis are possible.

The febrile period without treatment can last up to 3 weeks. Then the temperature decreases by accelerated lysis over several days, but in the afebrile period, repeated waves of apyrexia may occur. During the convalescence period, complications may develop - myocarditis, cardiovascular failure, encephalitis, etc. The total duration of the disease often ranges from 4 to 6 weeks.

Complications of Tsutsugamushi Fever

In severe cases of the disease, myocarditis, thrombophlebitis, pneumonia, lung abscess, gangrene, and glomerulonephritis are possible. With timely and adequate therapy, body temperature normalizes within the first 36 hours of treatment, and complications do not develop. The prognosis depends on the severity of the disease and complications. Mortality without treatment varies from 0.5 to 40%.

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Diagnosis of Tsutsugamushi fever

Tsutsugamushi fever is differentiated from other rickettsioses (tick-borne typhus of Northern Asia, Marseilles fever), dengue fever, measles, infectious erythema, secondary syphilis, pseudotuberculosis.

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Laboratory diagnostics of tsutsugamushi fever

Hemogram changes are non-specific. The most important are detection of specific antibodies in the RSK or RIGA, immunofluorescence method and ELISA. It is possible to set up a bioassay on white mice with subsequent isolation of pathogens or cultivation of microorganisms on a cell culture.

Treatment of tsutsugamushi fever

Etiotropic treatment of tsutsugamushi fever is carried out with tetracycline drugs (doxycycline 0.2 g once a day, tetracycline 0.3 g 4 times a day) for 5-7 days. Alternative drugs - rifampicin, macrolides, fluoroquinolones - are used in average therapeutic doses. Short courses of antibiotics contribute to the development of relapses. Complex pathogenetic treatment includes detoxification treatment of tsutsugamushi fever, the use of glucocorticosteroid drugs, cardiac glycosides.

How is tsutsugamushi fever prevented?

Tsutsugamushi fever can be prevented by carrying out the following measures: disinsection and deratization in natural biotopes near people, extermination of rodents, use of repellents and protective clothing, clearing the area of bushes. Specific immunoprophylaxis of tsutsugamushi fever has not been developed, vaccination of the population with a live attenuated vaccine (used according to epidemiological indications in endemic areas) has proven to be ineffective.