Scrub typhus: causes, symptoms, diagnosis, treatment, prognosis, and prevention

Scrub typhus, also known as tsutsugamushi disease, tsutsugamushi fever, or mite-borne typhus, is a natural focal disease caused by Orientia tsutsugamushi transmitted mainly by mites on rodents, characterized by high fever, septicemia, rash, eschar, and lymphadenopathy.


Causes

The pathogen is Orientia tsutsugamushi, formerly known as Rickettsia tsutsugamushi.

The pathogens are (0.3 - 0.5) μm x (0.8 - 2.0) μm, bispherical or short rod-shaped, Gram-negative, and arranged in pairs or in stacks near the nucleus in the cytoplasm. The pathogen is sensitive to heat and chemical disinfectants, can be inactivated at 55 °C for 10 minutes, and can be eliminated quickly in 0.5% phenol. However, it has a strong resistance to low temperature.

Epidemiology

Source of infection

The disease is mainly prevalent in rodents, and there are more than 20 pathogenic animals, mainly yellow-haired rats, striped field mice, and yellow-breasted rats. Mice and rats are mostly asymptomatic after infection, and pathogens are stored in the body for a long time, so they are the main source of infection. Although humans have pathogens in their blood after infection, they are not an important source of infection because mite bites are accidental.

Modes of transmission

The main transmitter is mites. Mite larvae acquire pathogens from infected animals, and they still carry pathogens after developing into adults, and the pathogens can be carried in eggs. When second-generation larvae infected with pathogens bite healthy rats, rats are infected.

Human-to-human transmission is absent.

Susceptibility

Humans are generally susceptible to the pathogen. Specifically, farmers, adolescents who frequently come into contact with grasslands, and workers in the field are susceptible to the disease. Patients can acquire lasting immunity to the same strains of pathogen after infection, and immunity to different strains can only maintain for several months.

Pathogenesis

The basic pathological change of the disease is generalized small vessel vasculitis, which causes acute interstitial inflammation of organs, vasculitis, and periangitis, leading to congestion, edema, cell degeneration, and necrosis of parenchymal organs.

After bites by chigger mites, papules, ulcers, or eschars may occur locally. Pathogens replicate and enter the blood circulation through the lymphatic system, causing septicemia. The toxin released by dead pathogens is the main cause of the disease, which can cause inflammatory lesions, degenerative lesions, and septicemia of various organs.

The systemic lymph nodes are mildly enlarged, and the lymph node enlargement near the ulcer or eschar is more prominent. Central necrosis may be present. Visceral congestion, severe splenomegaly, mild hepatomegaly, and focal necrosis are visible. Focal or diffuse myocarditis may be accompanied by hemorrhage and mild degeneration. Pulmonary congestion, bronchial pneumonia, and pleural effusion are seen. Lymphocytic meningitis and small hemorrhagic spots in the brain stem can be seen. The kidneys sometimes present with extensive acute inflammation. The gastrointestinal tract, especially the lower ileum, is often hyperemic.

Typhus nodules are also seen in this disease. Monocytes, plasma cells, and lymphocytes infiltration around small blood vessels are present, but swelling of endothelial cells in the tunica intima of blood vessels is not obvious, and thrombosis is less common.


Signs and Symptoms

The incubation period is 4 - 20 days, often 10 - 14 days, averagely 10 days.

Prodromal symptoms are generally absent. Sudden onset and rapid rise of body temperature, up to 39 - 41 °C, are present. Continuous fever, remittent fever, or irregular fever persist for 1 - 3 weeks. Fever is often accompanied by chills or rigors, severe headache, general soreness, fatigue, drowsiness, decreased appetite, nausea, vomiting, facial flushing, conjunctival congestion, photophobia, insomnia, and cough. Individuals may also have orbital pain. Irritability, delirium, hearing loss, tonic spasm, drowsiness, and coma may occur in severe patients, and meningeal irritation and pathological reflexes can occur.

Eschars and ulcers

Eschars and ulcers are the characteristics of this disease, which can be seen in 70% - 100% of patients. After bites by chigger mite larvae infected with Orientia tsutsugamushi, red papules occur locally, without pain and pruritus, developing into blisters. After necrosis and hemorrhage, black crusts appear, which are termed eschars. Eschars are round or oval, 2 - 15 mm in diameter, with red halos, with raised edges. Decrustation is followed by ulceration. Ulcers are with pale red granulation tissue in the base, with serous exudate initially. With the gradual reduction of serous exudate, a smooth and depressed surface is formed. Occasionally, secondary suppuration may occur. There are usually 1, occasionally 2 - 3, eschars or ulcers in most patients, but the number of eschars or ulcers can be up to 11. Because chigger mite larvae have a tendency to invade the moist, odorous, and oppressed sites in the human body, eschars are more common in the axilla, scrotum, external genitalia, groin, perineum, perianal areas, and sites oppressed by girdles, but can also be seen in the head, neck, chest, back, abdomen, breasts, and limbs. Eschars are often visible 1 - 2 weeks before onset.

Lymphadenopathy

The lymph nodes near the eschars are often noticeably swollen and often accompanied by pain and tenderness. Generalized superficial lymph node enlargements are also common. These enlarged lymph nodes are movable, as large as pigeon eggs, as small as broad beans.  more common in the groin, axilla, and postauricular areas, subsiding slowly, and often palpable in the recovery period.

Rashes

Rashes occur 2 - 8 days after onset. Rashes occur at onset or 14 days after onset in few patients. Skin lesions are different sized, 2 - 5 mm in diameter, dark red, mostly congestive, rarely hemorrhagic maculopapular rash, without pruritus, mainly on the trunk, progressing into extremities, rarely on the face, palms, and soles. These rashes may fuse with each other and gradually subside in 3 - 7 days, without scales, with pigmentation. Sometimes, enanthem or hemorrhagic spots can occur on the soft palate, hard palate, and buccal mucosa 7 - 10 days after onset.

There are some mild patients in some endemic areas. Their clinical manifestations are fever, headache, rash, and lymphadenopathy.

Hepatosplenomegaly

Hepatomegaly is seen in 10% - 30% of patients, and splenomegaly is visible in 30% - 50% of patients, with soft texture, with smooth surface, without tenderness.

Others

The tip and edges of tongue is often red, with white or yellow, thick coating. Conjunctival congestion is one of common signs. Subconjunctival hemorrhage is present in about 5% of patients. Varicose veins at the fundus, blurred optic disc edges, edema, and fundus hemorrhage can be seen. Some patients present with dermahemia, so they have flushing on the face or whole body. Myocarditis is more common, heart rate can reach more than 120 beats per minute, heart sounds and pulses are weak, flat or inverted T wave can be seen in electrocardiogram, and conduction block may occur, Heart failure and circulatory failure can occur in severe patients. Pulmonary signs vary depending on the severity of the disease. No obvious pulmonary signs can be found in mild patients. Interstitial pneumonia may occur in severe patients. Dyspnea may cause cyanosis. If with secondary bacterial infections, dry and moist rales can be heard. In addition, systemic hypersensitivity, testicular swelling and pain, scrotal swelling and tenderness, low back pain, and abdominal distension can also occur.

Critical patients present with severe multiple organ dysfunction, heart failure, kidney failure, circulatory failure, and hemorrhage, such as nasal hemorrhage and gastrointestinal hemorrhage, may occur, and disseminated intravascular coagulation can also occur.

Untreated patients may present with different signs of neurological deficits, such as deafness, dysarthria, and dysphagia, but all are temporary except that deafness may last for months.

In the untreated patients, the duration of fever is about 2 weeks, followed by a recovery period of 4 - 6 weeks. Due to various antigenic variations, the disease may often relapse.


Histopathology

Focal or generalized vasculitis and periangitis can be seen, mostly in the lung, brain, heart, and kidney. Perivascular monocytes, lymphocytes, and plasma cells infiltration can be visible. Vascular endothelial cell edema, as well as rupture and necrosis of blood vessel walls, can be present in severe patients. The pathogens can be detected in vascular endothelial cells, macrophages, and myocardial cells of various organs of patients.


Diagnosis

Ulcers and eschars on the bite sites and transient rashes are important clinical features of the disease. On the second week of the disease, positive results in Weil-Felix reaction tests with proteus oxk antigen can be seen in about 50% of patients. Specific antibodies can be detected with indirect immunofluorescence.Diagnosis can be based on the clinical findings and laboratory results.


Treatment

Macrolides, such as erythromycin, roxithromycin, azithromycin, clarithromycin, have a good effect against typhus.

Tetracyclines, such as tetracycline, doxycycline, and minocycline, are effective to treat typhus, but are contraindicated in children aged under 8 years, pregnant women, and lactating women.

Chloramphenicol has a good effect for the treatment of typhus. Because chloramphenicol can induce aplastic anemia, it should not be preferred. Chloramphenicol are contraindicated in young children, pregnant women, and lactating women.

Quinolones, such as ofloxacin, ciprofloxacin, pefloxacin, fleroxacin, lomefloxacin, and enoxacin, can be administered, but contraindicated in children aged under 8 years, pregnant women, and lactating women.

In addition, penicillins such as ampicillin, cephalosporins such as ceftazidime, cephaloglycins such as cefoxitin, carbapenems such as imipenem, monobactams such as aztreonam, and aminoglycosides such as amikacin have no therapeutic effect in the disease. The pathogens are parasitic in cells, and these antibiotics are difficult to enter the cells, so these antibiotics have no therapeutic effect.


Prognosis

If untreated, mortality ranges from 0 to 30%, depending on virulence and resistance factors. After prompt treatment, there are generally no deaths. Secondary and tertiary episodes caused by different serotypes are generally mild, without eschars and rash. The pathogens are still in the lymph nodes 1 year after recovery, suggesting that reactivation may occur during immunosuppression.


Prevention

Mites, house mice, and wild rats should be eliminated. Parasiticides and protective clothes can be used. Oral doxycycline weekly can be useful in the epidemic area.