Tsutsugamushi fever: causes, symptoms, diagnosis, treatment

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

Tsutsugamushi fever: brief historical information

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

Epidemiology of tsutsugamushi fever

The reservoir and sources of the pathogen are mouse rodents, insectivorous and marsupials, as well as their ectoparasites, red tick mites. Animals carry the infection in a latent form, the duration of their infection period is not known. In ticks, infectivity persists for life, transvirus and transfacial transfer of rickettsia are carried out. A sick person does not present an epidemiological danger.

The transmission mechanism is vector-borne, the carriers are red-tick mites, parasites on animals and humans

The natural susceptibility of people is high. Postinfectious immunity is homologous and prolonged, however, in endemic foci there may be cases of reinfection.

Tsutsugamushi fever occurs in many countries of Central, East and South-East Asia and the Pacific Islands (India, Sri Lanka, Malaysia, Indonesia, Pakistan, Japan, South Korea, China, etc.). In Russia, natural foci of infection are known in the Primorsky Territory, the Kuril Islands, Kamchatka, and Sakhalin.

In endemic areas, the tsutsugamushi fever is recorded as sporadic cases and group outbreaks, mass explosions among visitors are described. Summer seasonality is noted with a peak in July-August, which is explained by the biological activity of ticks at this time. Persons of all age and sex groups are ill (mainly engaged in agricultural work in river valleys with shrubby and grassy thickets - a biotope of red-tick mites).

[1], [2], [3], [4]

Causes of tsutsugamushi fever

The tsutsugamushi fever is caused by a small polymorphic gram-negative rod Orientia tsutsugamushi, which belongs to the genus Orientia of the family Rickettsiaceae. Unlike representatives of the genus Rickettsia, orientations lack some constituents of peptidoglycan and LPS (muramic acid, glucosamine and oxidized fatty acids) in the cell wall. The causative agent is cultivated in mites, transplantable cell cultures and the yolk sac of a chick embryo, and parasitizes in infected cells in the cytoplasm and in the nucleus. It is subdivided into 6 serological groups, has a common antigen with protease OX ₁₉.

[5], [6], [7], [8]

Pathogenesis of Tsutsugamushi fever

The place of the tick bite is the primary affect. Lymphogenous pathway from the entrance gateway causes pathogens to enter the regional lymph nodes, lymphangitis and regional lymphadenitis are formed. After the initial accumulation of rickettsias, a phase of hematogenous dissemination develops in the lymph nodes. Propagation of pathogens in the cytoplasm of the body cells, especially in the vascular endothelium, explains the development of vasculitis and perivasculitis - a key link in the pathogenesis of tsutsugamushi fever. The small vessels of the myocardium, lungs and other parenchymal organs are mostly affected. Desquamation of endothelial cells is the basis for further granuloma formation similar to typhoid fever, but histological changes in vessels with tsucugamushi fever are less pronounced and do not reach the stage of development of thrombosis and necrosis of vascular walls, as in 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 the severity of the course of the disease differ significantly.

Primary affect occurs not in all patients. It can be detected already at the end of the incubation period in the form of a small (up to 2 mm in diameter) condensed spot of hyperemia. This is followed by a rapid development of chills, a sense of weakness, a severe headache, insomnia. There may be myalgia and arthralgia. Body temperature rises to high figures. Primary affect is transformed into a vesicle, and then gradually, for many days, into a sore with a peripheral zone of hyperemia and into a scab. Simultaneously there is a regional lymphadenitis. Further, the primary affect is retained until 2-3 weeks.

When examining patients from the first days of the disease, symptoms of tsutsugamushi fever are noted : congestion and puffiness of the face, pronounced conjunctivitis and scleritis. Less than half of patients on the 5th-8th day of the disease appear on the chest and stomach spotted rash, in the following the elements of the rash become maculopapular, spread to the limbs, without affecting the palms and soles. The frequent absence of primary affect and exanthema greatly complicates the diagnosis of zuggamushi fever.

Exanthema persists on average for a week. During this period, pronounced intoxication develops, generalized lymphadenopathy is formed, (which distinguishes the disease from all other rickettsiosis), tachycardia, muffled heart tones, systolic murmur, lowering of blood pressure. More often than with other rickettsiosis, myocarditis develops. 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 the intoxication increases, manifestations of encephalopathy increase (sleep disturbance, headache, agitation). In severe disease, delirium, sopor, convulsions, development of meningeal syndrome, glomerulonephritis are possible.

A febrile period without treatment can last up to 3 weeks. Then there is a decrease in temperature with accelerated lysis for several days, but in a febrile period, repeated waves of apyrexia may occur. In the period of convalescence, complications such as myocarditis, cardiovascular insufficiency, encephalitis and others may develop. The total duration of the disease is often from 4 to 6 weeks.

Complications of tsutsugamushi fever

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

[9], [10], [11]

Diagnosis of tsutsugamushi fever

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

[12], [13], [14]

Laboratory diagnostics of tsutsugamushi fever

Hemogram changes are nonspecific. The most important are the detection of specific antibodies in DSC or RIGA, immunofluorescence method and ELISA. It is possible to place 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 preparations of tetracycline series (doxycycline 0.2 g once daily, tetracycline 0.3 g 4 times per 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, use of glucocorticosteroid preparations, cardiac glycosides.

How is Tsutsugamushi prevented?

Tsutsugamushi fever is prevented if the following measures are carried out: disinfestation and deratization in natural biotopes near the location of people, destruction of rodents, use of repellents and protective clothing, clearing of the territory from bushes. Specific immunoprophylaxis of tsutsugamushi fever has not been developed, vaccination of the population with live attenuated vaccine (used in epidemic indications in endemic areas) has proved ineffective.