murine typhus fever



Overview

Epidemic typhus, also known as lice-borne typhus or typical typhus, may recur months to years after suffering from epidemiologic typhus, known as relapsing typhus, also known as Brill-Zinsser disease. It is an acute infectious disease transmitted by Rickettsia prowazekii through body lice. It is clinically characterized by persistent high fever, headache, petechiae-like rash (or maculopapular rash) and central nervous system symptoms, and the natural course of the disease is 2 to 3 weeks.

Etiology

The causative agent of the disease is Rickettsia prowazekii, which is parasitized in the cytoplasm of vascular endothelial cells in humans and animals and in the epithelial cells of the intestinal wall of the human louse, and it also adheres to erythrocytes and platelets in rickettsialemia. Its basic form is a tiny spherical rod, arranged in chains along the long axis. However, it is polymorphic in the developmental stage in the louse intestine, and can be spherical, short rod-shaped, rod-shaped or long thread-like. 0.3-1 μm × 0.3-0.4 μm, Gram-negative staining. The chemical composition and metabolites of the pathogen are proteins, sugars, fats, phospholipids, DNA, RNA, various enzymes, vitamins and endotoxin-like substances. The lipopolysaccharide layer of its cell wall has endotoxin-like effects. Rickettsia prowazekii is sensitive to heat, ultraviolet light, and general chemical disinfectants, and can be inactivated in 30 minutes at 56°C. It is more tolerant of low temperatures and drying, and can survive for several months in dry lice feces.

Symptoms

Generally, it can be divided into typical typhus and light typhus, and there is also recurrent typhus.

1. Typical typhus

The incubation period is 5 to 21 days, with an average of 10 to 12 days. A few patients have 2 to 3 days of prodromal symptoms, such as fatigue, headache, dizziness, chills, low fever and so on. Most of the patients have an acute onset of illness, accompanied by chills, severe and persistent headache, peripheral muscle pain, and congestion of the conjunctiva and face.

(1) Fever The temperature peaks on the second to fourth day (39-40℃ or more), with an insistent fever in the first week and a tendency to flaccid fever in the second week. The fever usually lasts for 14 to 18 days, and then the body temperature rapidly recedes to normal within 2 to 4 days. In recent years, the reported cases, the fever pattern is mostly flaccid or irregular, which may be related to the application of antibacterial drugs.

(2) Rash is seen in more than 80% of the cases and is an important sign of the disease. The rash appears on the 4th to 6th day of the disease, and is first seen on the chest, back, axilla, and sides of the upper arm, and then rapidly develops to the whole body within one day. There is usually no rash on the face and fewer rashes on the lower extremities. The rash is round or oval, about 2-4mm in diameter, initially bright red macules, which fade when pressed, and then turn into dark red or petechiae. The rash subsides in 5-7 days, and the petechiae-like rash may last for 1-2 weeks, leaving brownish-yellow spots or flakes.

(3) Neurological symptoms: Obvious and early onset, manifested by panic, excitement, severe headache, onset of mental retardation, delirium, occasional meningeal irritation, muscle and tongue tremor, coma, incontinence, dysphagia, hearing loss, and so on.

(4) Symptoms of cardiovascular system: The increase in heart rate is generally proportional to the increase in body temperature, and gallop rhythm and arrhythmia may occur when accompanied by toxic myocarditis. Shock or hypotension or even water loss, microcirculatory disorders, cardiovascular and adrenal hypofunction may occur.

(5) Other symptoms may include cough, chest pain, shortness of breath, nausea, vomiting, loss of appetite, constipation, abdominal distension, etc. Occasionally, there may be jaundice, cyanosis, and renal hypoplasia. Mildly enlarged spleen, hepatomegaly in some cases.

2. Mild typhus

Mild cases are more common and may be related to the immunity level of the population, which is characterized by:

(1) Shorter duration of fever (8-9 days) and lower fever (around 39℃);

(2) Less severe toxemic symptoms, but still with significant peripheral pain;

(3) The rash is a congestive maculopapular rash, which is seen on the chest and abdomen, and there is also a certain percentage of people without rash;

(4) Neurologic symptoms are mild and of short duration, mainly characterized by headache and excitement;

(5) Hepatosplenomegaly is rare.

3. Recurrent typhus

Mostly seen in Eastern Europe and Eastern Europeans migrated to the United States, domestic rarely reported this disease. The main clinical manifestations can be summarized as follows:

(1) A mild form of the disease, with mild toxemia and central nervous system symptoms;

(2) Flaccid fever with a duration of 7 to 11 days;

(3) No rash, or only a sparse maculopapular rash;

(4) Disseminated, not seasonal, with a significantly higher incidence in older age groups.

Laboratory tests

1. Routine blood and urine tests

The white blood cell count is mostly within the normal range. Platelet count is generally decreased, and eosinophils are significantly reduced or absent. Proteinuria is common, with occasional red and white blood cells and tubular pattern.

2. Serum immunologic examination

It is advisable to take double or triple serum specimens (initial admission, the second week of the disease and the recovery period), and those with more than 4-fold increase in potency have diagnostic value. Commonly used tests are the exophthalmos test, complement binding test, rickettsial agglutination test, indirect hemagglutination test. Although the specificity of exofibrio test is poor, but because the antigen is easy to obtain and save, so it is still widely used; its principle is that some rickettsiae are partly the same as the antigen of Aspergillus OX19, OXK, or OX2, so the patient’s serum can produce agglutination reaction to the relevant Aspergillus strains. The agglutination potency of sera of epidemic typhus patients against OX19 strain is generally more than 1:320, but often reaches a meaningful level or peak at the end of the 2nd week or during the recovery period; then the potency decreases rapidly, and becomes negative within 3~6 months.

3. Pathogen isolation

Not applicable to the general laboratory. Rickettsiaemia usually appears within 1 week after the disease, it is appropriate to collect blood for inoculation in the abdominal cavity of guinea pigs or in the yolk sac of chicken embryos before the application of antimicrobial drugs; or collect body lice on the patient to be kept in the laboratory for observation, and when the lice die of morbidity and disease, smear staining is made to check for rickettsiae. Guinea pigs are sensitive to Rickettsia prowazekii. 3~5ml of blood from patients with early onset of the disease can be injected into the abdominal cavity of male guinea pigs, and after 7~10 days, the animals will show a febrile reaction, and then the sphincter and peritoneum will be taken for scraping and examination, or tissues of the brain, adrenal glands and spleen will be taken for smearing, and then microscopic examination after staining can be done, and a large number of rickettsiae can be found located in the cytoplasm. The reaction of guinea pig scrotum is negative, or there is only mild redness without obvious swelling, which can be used as a reference for differentiating from endemic typhus.

4. Molecular biology examination

Detection of Rickettsia prowazekii specific DNA by DNA probe or PCR method has the advantages of rapidity, specificity and sensitivity.

5. Others

Cerebrospinal fluid should be examined if there are signs of meningeal irritation. The appearance of cerebrospinal fluid is mostly clarified, with a slight increase in mononuclear cells and protein, and normal sugar and chloride. Electrocardiogram may show myocardial damage, such as low voltage, T wave and S-T segment changes, etc. A few patients may have changes in liver and kidney function.

Diagnosis

1. Epidemiologic data

Local epidemiological situation, favorable season, history of living in the infected area, history of contact with lice carriers and the possibility of being bitten by lice are important references for diagnosis.

2. Clinical manifestations

Characteristics of fever and fever course, date of onset of rash, skin rash characteristics and obvious central nervous system symptoms are helpful for diagnosis.

3. Laboratory examination

Characteristics of the blood picture, positive exophthalmos reaction, especially in the recovery period, the serum potency has more than 4 times increase compared with the early stage, which has diagnostic value, but can not be divided into different types. Conditional can be made Przewalski’s rickettsial agglutination reaction, complement binding test and immunofluorescence indirect staining method to detect specific antibodies for type identification. Positive results of animal inoculation are particularly diagnostic.

Treatment

1. General treatment

After admission to the hospital, patients should change clothes, exterminate lice and take bed rest. Keep the mouth and skin clean. Critically ill patients should pay attention to turn over diligently to prevent complications. Provide nutritious and easy-to-digest diet, supplement a large amount of vitamin B, C and enough water and electrolytes.

2.Pathogen treatment

Tetracycline antimicrobial drugs are effective against this disease. Generally, the symptoms start to reduce in more than ten hours after the use of the drug, and the fever completely subsides in 2-3 days. Doxycycline is a simple treatment with few side effects and satisfactory results. Recently, erythromycin and fluoroquinolones have been used to treat the disease with good results.

3. Symptomatic treatment

Physical cooling is the mainstay of hyperthermia, and small doses of antipyretic and analgesic drugs can be given when necessary. Adrenocorticotropic hormone can be given for a short period of time for those with severe toxemia symptoms, and infectious shock can be treated according to the tendency of hypovolemia or shock. For those with cardiac insufficiency, attention should be paid to reducing the cardiac load, and cardiotonic drugs such as trichothecene C or toxic trichothecene K can be used. For those with severe headache, analgesic and sedative drugs can be given.