Lecture on the fever caused by the larvae (Scrub Typhus Tsutsugamushi)

2021-01-31 12:00 AM

The Scrub Typhus is clinically characterized by fever lasting 2-3 weeks, accompanied by skin ulcers, systemic lymphadenopathy, and rash. 


Fever caused by larvae (often referred to as mite) is an acute infectious disease caused by Rickettsia Orientalis (or R. tsutsugamushi); the vector of disease transmission is Trombicula larvae (now called Leptotrombidium). The disease is clinically characterized by fever lasting 2-3 weeks, accompanied by skin ulcers, systemic lymphadenopathy, and rash. Treatment with chloramphenicol and tetracycline with good results. 

Typhoid fever has other names such as Tsutsugamushi disease, Japanese river fever, jungle typhus fever, tropical typhus fever ..., our country is called mite fever.

Research history

The disease has been known for a long time. But it was not until 1916-1921 that Leptotrobidium mite larvae were identified as vectors for disease transmission. In 1930, Japanese Nagayo isolated Rickettsia Orientalis in patient blood.


The disease is common in East Asian countries (China, Korea, Japan), Southeast Asian countries, India, the northern part of Australia, and the islands in the Western Pacific.


It is Rickettsia Orientalis (another name is R. tsutsugamushi). Was isolated for the first time in Japan. It has an independent respiratory system, has a yeast system but is incomplete, so it must live in the host cell. Giêmsa dye catches green to purple, is spherical, short rod-shaped, and thread-shaped. Arrange individually, in pairs, or in clusters in the cytoplasm of the host cell.

Has weak resistance. Easily killed by conventional antiseptics and high temperature.

Antigen structure: There are 2 types:

Specific antigens: Specific to each individual type, with many different antigen types representing a locality or a certain area. There is no cross immunization between the types, which makes it difficult to diagnose and prevent vaccine disease.

Nonspecific antigen: R. Orientalis has a polysaccharide antigen like the OXk antigen of the intestinal bacillus Proteus mirabilis. The serum reaction that uses P. mirabilis's Oxk antigen to detect antibodies in a patient with a fever is called the Weil-Felix reaction. This reaction is nonspecific but common, and easy to produce.

Pathogen and disease vector

Source of disease: are wild animals such as rodents (mainly mice), rabbits, Birds, or livestock (dogs, pigs, chickens) ...

Infection vector: Leptotrombidium (or Trombicula) akamushi and L. deliense larvae. mite larvae infected with R. Orientalis when sucking blood from a host carrying pathogen; then moth larvae develop into adults and lay eggs. Eggs hatch into larvae that already carry germs and are ready to suck blood (they can transmit germs through eggs to the third generation). These larvae will later infect other animals and humans by burning and sucking blood. Thus, the mite is both a host and an intermediate for disease transmission. Infection is maintained in the wild between mites and rodents etc. and the moth transmits pathogens through the moth's later generations. Sniffing and sucking human blood, transmitting R.orientalis to humans is just a coincidence.

Conditions of transmission: Leptotrombidium mounds usually live-in shrubs, moist grass bushes ... above are tall tree canopy; or in rocky caves with live rodents. Therefore, people often get sick with a fever when passing through or working in these places such as Army troops fighting, people hunting, slash-and-burn cultivation, etc., or when passing through streams, riverside areas, or rocky caves.

Sensitivity and immunity

People with high susceptibility to sick fever. The disease causes immunity. Local people are less susceptible and suffer from mild forms, and people in remote places are susceptible to severe forms. Reinfection may result from the acquisition of R. Orientalis with a different antigenic structure, in other regions.

Translation properties

Fever usually occurs in the hot and rainy seasons. Therefore, in the North of Vietnam, it is usually from May to October. In the South of Vietnam, fever happens all year round but is still highest in the rainy season.

The epidemic is often sporadic, scattered into small nests, in each area.

Mechanism of pathogenesis and pathology

Mechanism of pathogenesis

At the place of blood-sucking, a small pink maculopapular rash appears, then a papule, which is enlarged and then blisters, bursting with broken water and necrosis in the middle to create hard black scabs, scabs, leaving ulcers period 6-18 days)

From the ulcer R. Orientalis broke into the lymphatic system causing local lymphadenitis and then proceeded to cause systemic lymphadenitis, causing swelling and pain in the lymph nodes. At the same time, they break into the bloodstream to cause systemic endometritis, causing inflammatory damage in the organs.

The clinical condition is severe - mild, depending on many conditions such as Place of residence, the toxicity of each strain (fever in Japan, China has a high mortality rate but in Malaysia, it is an only mild disease., Indonesia often has typical ulcers, while in Malaysia it is rare to see ulcers). At the same time depends on the patient's resistance combined with the mechanism of allergic toxicity of the body against R. Orientalis.

The antibiotic did not kill R. Orientalis, only limited its development. Therefore, even with a specific treatment, R. Orientalis remains in the body for many months, in the lymph nodes, and causes relapse.

Pathological anatomy

The primary lesion of the disease is endometritis of the veins with infiltration of peri-vascular mononuclear cells. Due to inflammation in the endothelium will cause congestion, bleeding and even necrosis of the parenchyma of the organs:

Cardiovascular: Myocarditis, thrombophlebitis.

Respiratory: Interstitial pneumonia, bronchitis - lung

Kidney: Glomerulonephritis, interstitial nephritis.

Encephalitis, acute meningitis

Enlarged liver, spleen due to acute inflammation.

Systemic lymphadenitis, especially the local lymph nodes near the enlarged ulcer; can inflammation around the lymph nodes, gangrene.

Skin ulcers: Where the larvae bite, there is necrosis of the epidermis and subcutaneous tissue creating ulcers.

Skin rashes: Common macular rash with maculopapular rash and purpura.


Divide the clinical form

According to the clinical picture there can be:

Potential form.

Typical conventional form.


Heavy form.

Symptom clinical form

Typical conventional form


Average from 8 to 12 days, early is 6 days, and length is 21 days.


Symptoms of ulcer formation. But the patient did not know because there was no pain, burning or itching. The patient only knows when the fever is high and the disease is in the full stage.

Full play:

Toxic infection syndrome: Usually severe and is the early symptoms of the disease with the following manifestations:

Low-grade fever 1 to 2 days first, after persistent high fever; There are also many cases of sudden fever rising at 39-40 ° C on the first day like malaria. Persistent, persistent high fever around 40 ° C, plateau-shaped or intermittent type lasting 15 to 20 days, if left untreated. Temperatures and circuits often dissociate like typhoid. During the first 1-2 days there may be shivering fevers or cold thorns, followed by simple fever.

Neurotoxicity is usually severe, headache is the first sign, pain all over the head, headaches such as hammer, persistent for several days, possibly both eye fossa. Fatigue, irritability, dizziness, dizziness, lurching, tinnitus, trembling tongue, sweating, muscle aches as much as in Leptospirosis - sometimes drowsiness, gloom as in typhoid.

Ulcerative - lymphadenopathy - rash:

Ulcers: The proportion of patients with ulcers varies by country. In Vietnam, it is quite common about 80%, which is a sign that makes diagnosing the disease easy.

Location: ulcers are found in many places all over the body, usually in the young and moist skin. Commonly seen in the genitals; armpits, groin, anus, groin, back lumbar to limbs, back, chest, abdomen, neck, sometimes the sores are in quite unexpected positions such as the ear, navel, eyelids. So, to carefully examine all parts of the patient.

 Quantity: Commonly one ulcer, only rarely has 2 ulcers.

 Characteristics: Usually round or oval, the small diameter is 1mm, to large is 2 cm. If scabs are present, they are black, hard, and covered with a hard-edged papule. If the scab has peeled off, it will leave a concave sore, bright red, clean with no discharge, without pus, and the edge of the ulcer is usually higher than the skin surface. The patient is not aware of an ulcer because of absolutely no pain, no itching, no pressure, burning.


There are 2 types of lymphadenopathy:

 Primary regional lymphadenitis: near the area where the ulcer is caused by the bite of a nematode which is as large as apple seed, oval or possibly larger. Regional lymph nodes are usually larger than lymph nodes elsewhere. At first only more pain after pain, can inflammation around the lymph nodes. Regional lymph nodes usually appear with fever or 2-3 days after fever. It is the discovery of regional lymph nodes that help guide the search for ulcers.

 Secondary systemic lymphadenitis: Usually occurs after regional lymph nodes, but usually less swelling, mobility, and mild pain than regional lymph nodes. Common in the armpits, groin, neck, elbows. In Vietnam, usually, 100% of patients with fever have swollen lymph nodes.


It is a common symptom, but it also depends on the author and locality, particularly in Vietnam, about 70%.

 Appears at the end of week 1 and the beginning of week 2 of the disease.

 Usually maculopapular, ranging in size from millet to 1 cm in diameter. Grows all over the body (back, chest, abdomen, extremities) except palms, soles of the feet, about 10% has purpura.

Rash lasts from a few hours to a week.

Cardiovascular and cardiovascular syndrome:

It is very common to see cardiovascular damage in fever disease such as:

Vasodilation causes the skin to often ruddy, congestion of the eye conjunctiva with red blood rays (this is a symptom to distinguish from malaria and typhoid). Sometimes there are cases of subcutaneous bleeding, nosebleeds, gastrointestinal bleeding, coughing up blood ...

Or manifestations of myocarditis: blurred heart hour, extrasystole, decreased blood pressure.

Respiratory symptoms:

Atypical pneumonia or bronchitis may be present.

Symptoms in other organs:

Gastrointestinal: Usually apple stools during fever days, sometimes it may loosen for a few days. The liver and spleen can be enlarged, but usually only marginally visible, with little pain.

Urology: There may be protein in the urine, sometimes cylindrical, but only transient.

Recovery and recurrence:

Recovery: If treated with the right antibiotics, the fever will cut quickly. But if there is no antibiotic treatment and there are no complications, the fever usually lasts about 2-3 weeks (especially the fever is up to 27 days), the fever is gone. The disease recovers slowly, the convalescence lasts 1-2 weeks.

Recurrence: The recurrence rate is high, even though it has been treated with chloride at low or high doses. Relapses usually appear 5-14 days after the fever has been removed. There is a recurrence because chlorosis only sterilizes, cannot kill Rickettsia, so Rickettsia still exists in the lymph nodes.

Complications and death:

Complications: If left untreated, the disease can experience serious complications and often a cause of death such as:

Cardiovascular: Myocarditis, cardiomyopathy, septic shock ...

Respiratory: Pneumonia, pneumonia - severe bronchitis due to superinfection or Rickettsia itself.

They don't come, they don't.

Mortality: Mortality rates vary by region, depending on the toxicity of Rickettsia strains in each place.

Symptoms of other diseases

Potential form

There are no clinical manifestations, but an assay for complement combination reaction with Rickettsia (+). This can meet many, 10 times more than the disease with clear clinical manifestations.


Symptoms are mild, atypical, and easily misdiagnosed with other infectious fevers.

Heavy form

There are complications of cardiovascular, respiratory, neurological, hemorrhage, etc. easy to die.

Implementing the quadrants

Clinical symptoms

Especially the syndrome of fever and ulcer - lymphadenopathy - rash.


Live or traverse an epidemic zone.


Routine blood tests: little support for diagnosis because

Leukocytes: An erratically high or low 4,000 to 12,000 tends to be low during the first week and high in the last days of a fever. If the white blood cell is too high to think of superinfection. The acidophilia disappears in the early stages of the fever and reappears when the fever is gone.

Rate of blood sedimentation: Increases during fever, highest when recovering, and then gradually returns to normal.

Serum reactions

Weil-Felix reaction: The presumptive agglutination titer (when done once) is equal to and above 1/160. If done 2 times (1st time: take blood before the 10th day of the disease; 2nd time: take the 3rd or 4th week of the disease), when the 2nd agglutination titer increases ³ 4 times 1, it is called positive. Weil-Felix is ​​not specific, but because it is easy to implement, it is often used in practice.

Complement fusion reaction: Very specific over many years. Depending on the method, the positive precipitation titer ranges from 1/32 to 1/128.

Direct or indirect fluorescence immune response: The indirect method is easier to do than the direct method. Positive precipitation titer from 1/32, 1/64, 1/128 depending on the method.

In addition to the above reactions can cause serological reactions such as Passive erythrocyte agglutination, micro centration. Nowadays better techniques like PCR and Dot-Blot Immuno Assay Diptick and so on

Isolation of the pathogen: It is the most accurate method of diagnosis of fever. Take 1ml of the patient's blood and inject it into the peritoneum of mature white mice. After 7-15 days the rat can get sick. If mice are sick, they will be operated on to make prints and stained specimens according to the Romanovski-Giem sa method and detect pathogens on the specimen. Because the antibiotic is only effective at inhibiting Rickettsia, even if the patient is already taking antibiotics, even if the fever is gone for 5-6 days, it is still possible to isolate Rickettsia from the blood.

Differential diagnosis

In Vietnam, the disease needs to be differentially diagnosed with the following diseases:

Diseases caused by Leptospira spirochetes (Leptospirosis)

Similar to fever: sudden fever, red face, muscle aches, may have a rash, lymph nodes. The epidemic season is the rainy season, with epidemiological factors in mountainous areas ...

Other than a fever: Fever usually does not last more than 10 days, never has ulcers, often has significant liver-kidney damage, specific serum reaction is Martin-Pettit.


Like fever: fever lasting 2-3 weeks, dissociation pulse and temperature, also dyspepsia, digestive disorders, possibly myocarditis, bronchitis, pneumonia.

Other than a fever: The onset is usually more gradual, the rash in typhoid is less, sparse, only a few nodules in the lumbar region, the abdomen (the rash of fever is much, in the whole body) often has bloating, right pelvic fossa Padalka (+), never ulcer, myalgia, red eyes, Widal (+) serum reaction.

Dengue sauce

Like fever: Onset high fever, sudden, sometimes pulse and dissociation temperature, headache, arthralgia, congestive dilated skin, red eyes also have lymph nodes and rash ...

Other fever: Fever usually lasts only 6-7 days on average, sometimes with 2 episodes. Ban-haemorrhage usually grows at the time the fever is subsiding or the fever is gone (in a fever that grows when the fever is high), never having an ulcer.

Specific test: Red cell agglutination reaction with dengue virus (+).

Primary malaria

Like fever: Both high fevers last for many days, and all get sick when entering the mountainous areas.

Different from fever: Although primary malaria lasts for many days, there is a tendency to change into a periodic fever and have fevers in order: Hot - hot, sweating, and fever-free. Specific tests: Find malaria parasites in the blood.

Mouse rash

Although not popular met.

Same: All high fever, headache, arthralgia, macular rash on 4-5 days, leukocytes are also abnormally high.

Other than a fever: Mouse scarlet fever is caused by Rickettsia mooseri, starts not suddenly with fever, lymphadenopathy is a very small, mild painful reaction, even on the palm of the hand. The Weil-Felix test is (+) with OX19 and (-) with OXk.

Lice rash

The disease tends to disappear around the world. in Vietnam, the last outbreak was in 1944.

Fever-like: High fever, headache, red eyes, muscle aches, rash on both body and extremities, no rash in palms of hands or feet.

Different from fever: No ulcer, or more enlarged spleen than fever. Caused by Rickettsia prowazekii. The Weil-Felix test was positive for OX19 but (-) for OXk.

New type fever (Schichitonetsu's disease)

Also known as Schichitonetsu's disease, was discovered in Japan after World War II.

It was caused by Rickettsia sennetsu. The vector is Trombicula scutellaris and Trombicula pallida.

Like fever: also, high fever, lymphadenopathy, rash, Weil-Felix reaction also (+) with OXk.

Other than a fever: The epidemic season is a winter-spring season (the fever is summer), there may be no ulcers, less genital ulcers are common. The rash usually takes the form of measles, swollen lymph nodes, and pain is more common than fever.


Specific values

Sulfamide is effective with Rickettsia, but only used for mild form and nowadays rarely used because in fever, there is endothelial inflammation easily causing edema, embolism, if sulfamide treatment can easily damage the kidneys, kidney tubules.

The most common and effective antibiotics for hay fever are chlorocide and tetracycline. But these 2 drugs only have bactericidal effects, not kill bacteria. Therefore, Rickettsia still lives and exists in the lymph nodes, in the retinal system of the endothelium (even with enough treatment) for many days, months, and easily relapses.

Dosage and usage: Through the practice of fighting against fever in Vietnam to quickly cut fever and prevent a recurrence, the therapeutic dose and usage are as follows:

Starting at a high dose of 2 g tends to cut fever more quickly.

First day: 2g / day (for people ³ 50 kg). The following days: 1g / day.

Use until the fever is cut for 2-3 days; total dose is 6-7g (chlorosis and tetracycline doses are the same). In this way, the rate of recurrence is usually minor and mild. The use of high doses does not impair the antibody generation and therefore does not affect the analysis of the results of serum reactions. At the same time, the initial attack dose did not cause complications for the patient.

Can use doxycycline 100 mg x 1 tablet / day / adult. Use from 7 to 15 days.

Almost no antibiotic resistance has been seen in fever.

Combination of chlorosis or tetracycline with corticosteroid therapy: In some cases, after using antibiotics for a few days, the temperature still does not improve, it can be combined with cortancyl (if there are no contraindications) with a short average dose. Cortancyl tablets 5 mg ´ 4 tablets/day used for 2-3 days will lower temperature faster.

Symptomatic treatment

Water - electrolyte supplementation: in patients with fever, often persistent high fever, poor eating, and drinking, so electrolyte dehydration is easy. Therefore, it is necessary to give the patient oral and infusion.

Cardiovascular support: In fever or myocarditis, endocarditis, so it is necessary to use cardiovascular aids such as Ouabain, spactein, coramin, etc.

Resistance enhancement: vitamins, nutrition, diet.


Personal protection against stings by Wearing shorts, leggings, socks, boots, leggings, and sleeves in socks when entering wooded areas. Do not dry clothes, put on backpacks, or lie on the grass (is the main measure).

Killing mite larvae by DDT, 666, Malathion ... Rat-killing organization (costly and ineffective)

Do not use preventive antibiotics because they are less effective and expensive.

There is no vaccine for disease prevention.