typhus



OVERVIEW

Definition

Typhus is an acute infectious disease caused by rickettsial infection, which is a category C infectious disease under the regulations of China’s Infectious Disease Control Law.

The main manifestations of the disease are fever, headache, rash and so on [1-3].

It occurs mostly in cold areas and is more frequent in winter and spring.

Classification

Typhus is mainly divided into two types: epidemic typhus and endemic typhus.

Epidemic typhus

Also known as lice-borne typhus.

Caused by Rickettsia prowazekii infection, the time from infection to onset of disease is usually 10-14 days [2].

It can be categorized into three types: typical, mild and recurrent.

Endemic typhus

Also known as murine typhus.

It is caused by Rickettsia muridarum infection. The time from infection to onset is usually 1~2 weeks [2].

Morbidity

Typhus is one of the common insect-borne infections and is particularly prevalent in poor, crowded and unhygienic environments.

There have been no major epidemics of this disease in China since the 1960s, with disseminated cases and small epidemics in individual places [4].

In 2021, a total of 1,310 cases of typhus were reported in China, with a reported incidence of about 1/1 million [5].

Etiology

Causes of the disease

Typhus is caused by rickettsial infection and the basic conditions leading to epidemics are threefold.

Source of infection

The source of epidemic typhus infection is the patient with the disease.

The main source of endemic typhus is the house mouse. In addition, patients and cattle, sheep, pigs, horses and mules may also serve as sources of infection [1-2].

From the end of the incubation period to a few days after the fever subsides are infectious, the first week after the onset of the most infectious, generally not more than 3 weeks.

Transmission

Human lice as a vector, mainly for body lice, head lice, followed by pubic lice are generally not transmitted.

When a louse bites a patient, the rickettsiae will enter the louse with the blood, reproduce and grow, and cause the louse to die. When these lice bite the human body before dying, the rickettsiae will enter the human body along with the bite breaks, or scratches and other breaks due to itching.

Rickettsiae within dried lice feces can contaminate the air to form aerosols that can occasionally infect the body through the respiratory tract or conjunctiva of the eyes.

When the patient becomes febrile or dies, the human louse will migrate to a new host and spread in a human-louse-human manner [1-3].

Rat fleas are the main vector.

After the bite of the rat flea of the sucking rat, the flea feces containing pathogens can be discharged on the skin, or after the flea is crushed, the pathogens inside the flea enter the human body through the scratches, and spread in the way of rat-flea-human.

The pathogens in the dried flea feces may occasionally form aerosols and infect humans through the respiratory tract and conjunctiva.

Susceptible population

The population is generally susceptible, with strong and persistent immunity after infection.

People living in poor, overcrowded and unhygienic conditions are more susceptible.

Pathogenesis

The occurrence of typhus is mainly related to vasculopathy caused by pathogens, toxin-induced toxemia, and metaplasia [2].

After the pathogen invades the human body, it first multiplies in the endothelial cells of small blood vessels and capillaries, causing vascular endothelial cell lesions.

When the cytolysis ruptures, a large number of rickettsiae enter the bloodstream to form toxemia, which infects the endothelial cells of several organs of the body.

The direct damage to the vascular endothelial cells by a large number of rickettsiae and the endotoxin released by them will cause systemic microcirculation disorders, and the corresponding clinical symptoms of tissue and organ damage will be manifested in the clinic [2].

Symptoms

Main symptoms

Typhus can be divided into epidemic typhus and endemic typhus, of which epidemic typhus can be divided into three types: typical, mild and recurrent.

Epidemic typhus

Fever: the onset of disease is rapid, body temperature is about 39℃, may be accompanied by chills, high fever lasts for 2~3 weeks can gradually return to normal.

Rash: first seen on the chest and back, can be all over the body, but palms, soles and face mostly without rash. It starts as a bright red rash, which can be discolored by pressing, and later turns into dark red.

Central nervous system symptoms: headache, dizziness, insomnia, tinnitus and hearing loss, and even slow reaction, delirium, mania, etc..

Liver and spleen enlargement: about 90% of patients have mild splenomegaly, and a few patients have hepatomegaly.

Others: it may be accompanied by poor appetite, nausea, vomiting, constipation, abdominal distension and other gastrointestinal symptoms.

Most of the disseminated cases in China are of this type.

Compared with typical cases, its fever is short, body temperature is mostly below 39 ℃, there may be obvious headache and generalized pain, but seldom appear consciousness disorder, and often no rash.

Most of them have mild manifestations and are rare in China.

There is a past history of epidemic typhus, and after the first infection or disease, the rickettsiae are not completely removed, but persist in the body for a long time. When the body’s immunity decreases, it can cause the latent Rickettsia prowazekii to reproduce again, leading to disease recurrence.

Endemic typhus

Fever: the body temperature is mostly around 39℃, may be accompanied by chills, high fever lasts for 9~14 days and can gradually return to normal.

Rash: compared with epidemic typhus, the number of rashes is small, but the soles of the feet and palms of the hands are sometimes visible, and the rashes can subside after a few days, usually leaving no traces.

Central nervous system symptoms: Compared with epidemic typhus, the central nervous system symptoms, such as headache and dizziness, are mild.

Liver and spleen enlargement: about 50% of patients have mildly enlarged spleen, and fewer have enlarged liver.

Other: may be accompanied by poor appetite, nausea, vomiting, constipation, abdominal distension and other digestive symptoms.

Complications

Common complications of typhus include toxic myocarditis, bronchopneumonia, otitis media and mumps.

Toxic myocarditis

Increased heart rate, panic, chest tightness, shortness of breath and chest pain may occur.

Bronchopneumonia

Coughing, coughing up sputum, breath holding and other manifestations can be seen when combined with bronchopneumonia.

Otitis media

In combination with otitis media, hearing loss, earache, tinnitus, and a feeling of stuffiness in the ear may occur.

Mumps

People with parotitis may experience pain in the face, pain on pressure, swelling of the face, etc.

Consultation

Department of Medicine

Department of Infectious Diseases

If you have scratched your skin after being bitten by mosquitoes, or if you have traveled to a typhus-prone area and developed a rash, fever, headache, or dizziness afterward, it is recommended that you consult the Department of Infectious Diseases.

Preparation for medical treatment

Preparation for medical consultation: registration, preparation of documents, FAQs

Tips for the doctor

A full body checkup may be required, so wear loose-fitting clothing to make it easier for the doctor to check the rash and perform related diagnostic procedures.

If you have a fever, you may apply warm towels to your forehead or armpits to lower the temperature.

Preparation Checklist

Pay particular attention to the time of onset of symptoms, special manifestations, etc.

Is there a rash, itchy skin, etc.?

Is there fever? What is the highest temperature?

Are there chills, muscle aches?

Is there dizziness, headache, nausea, vomiting, etc.?

When did the above symptoms appear?

Is there any recent history of skin trauma?

Are there any rat flea bites?

Have you recently traveled to an area with a high incidence of typhus?

Test results in the last 1 month that can be brought to the doctor’s office

General laboratory tests: routine blood tests, blood biochemistry, etc.

Serologic tests: Rickettsia agglutination reaction, exofibrio reaction test, complement binding test, etc.

Nucleic acid test: rickettsial nucleic acid test.

Medication used in the last 1 week, if there is a medicine box or package, you can bring it to the doctor

Antipyretics: ibuprofen, acetaminophen, etc.

Antibiotics: doxycycline, dimethylaminotetracycline (minocycline), etc.

Diagnosis

Diagnosis is based on

medical history

Patients with this disease may have the following epidemiologic history.

A history of scratching the skin after being bitten by rat fleas or human lice.

Traveled to an area with a high incidence of typhus.

Clinical manifestations

Fever, rash, headache, dizziness, poor appetite, nausea and vomiting may be present.

When combined with related complications, corresponding symptoms may appear, such as combined with bronchopneumonia, there may be coughing, coughing up sputum, breath-holding and so on.

Among them, the number of rashes of epidemic typhus is higher and can spread all over the body, and the number of rashes of endemic typhus is less. Dizziness and headache are less severe in endemic typhus than in epidemic typhus.

General Laboratory Tests

The leukocyte count in epidemic typhus is mostly within the normal range, neutrophils are often elevated, eosinophils are reduced or absent; platelets are often reduced [4-7].

The total number and classification of leukocytes in endemic typhus are mostly normal, and thrombocytopenia may occur in a few cases early in the course of the disease [4-7].

Aspartate aminotransferase (AST), glutamate aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) are mildly elevated in serum biochemistry in about 90% of patients with endemic typhus [2].

Serologic tests

Both epidemic typhus and endemic typhus exophthalmos tests can be positive, but the antibody potency of endemic typhus is lower than that of epidemic typhus.

The diagnosis of the disease is facilitated when the antibody potency of the assay is >1:160 or when there is a 4-fold or greater increase in the course of the disease.

Agglutination of rickettsial particle antigen with the patient’s serum can be used to differentiate between epidemic and endemic typhus.

Assay potency ≥1:32 has diagnostic significance, and the positive rate of patients with epidemic typhus is 50% to 70% in the first week of the disease, and can reach more than 90% in the second week, with high specificity [4-7].

It can be used to identify epidemic and endemic typhus.

It can be used for epidemiologic investigation and early diagnosis, but cannot differentiate between epidemic and endemic typhus.

Indirect immunofluorescence test using typhus rickettsiae as antigen and checking specific IgM and IgG antibodies can be used to differentiate from endemic typhus.

Nucleic acid test

DNA probe or PCR method is used to detect the nucleic acid of rickettsiae in the patient’s blood, if the result is positive, it will help early diagnosis.

Cerebrospinal fluid examination

In patients with positive meningeal irritation signs examined by a physician, lumbar puncture cerebrospinal fluid examination is feasible, which shows slightly higher pressure, cerebrospinal fluid leukocytes and protein, and glucose is often in the normal range [2].

Pathogen isolation

It is generally not used for clinical diagnosis.

Inoculate the blood of patients in the febrile period into the abdominal cavity of male guinea pigs, observe the swelling of the scrotum, and take their brain, adrenal glands, spleen, testicular sheath or peritoneum, smear or scrape staining microscopic examination, observe the presence or absence of rickettsiae.

Differential diagnosis

Typhus can cause symptoms such as rash, fever, headache, nausea and vomiting, which are not specific and need to be differentiated from diseases with similar symptoms under the guidance of a doctor.

There are also two types of typhus, which also need to be differentiated between two different types, i.e., epidemic and endemic typhus.

Differentiation of diseases with similar symptoms

The rash caused by typhus needs to be differentiated from atopic dermatitis, urticaria, and atopic dermatitis.

Fever caused by typhus needs to be differentiated from typhoid fever, regression fever, and pneumonia.

Headache and dizziness caused by typhus need to be differentiated from meningitis, subarachnoid hemorrhage and brain tumor.

Nausea and vomiting caused by typhus need to be differentiated from chronic gastritis and duodenal ulcer.

Different types of identification

The differentiation between epidemic typhus and endemic typhus is shown in the table below.

Rat fleas

Disease is often severe and mild

Sickness

More severe

Mild

Rash is numerous and may be sparse all over the body.

Rash

Rash is numerous and may be all over the body

Scarce

Neurologic symptoms Headache and dizziness are evident Headache and dizziness are relatively mild

Neurologic symptoms

Headache and dizziness are obvious

Headache, dizziness relatively mild

Thrombocytopenia common uncommon

Thrombocytopenia

Common

Uncommon

Exofetal test can be strongly positive, antibody potency can be 1:320～1:5120 antibody potency is relatively low, mostly in the range of 1:160～1:640

Exoflagellate test

Strongly positive, antibody potency up to 1:320～1:5120

Antibody potency is relatively low, mostly in the range of 1:160 to 1:640.

Treatment

Aim of treatment: alleviate symptoms, control disease development, prevent and reduce complications.

The principle of treatment: to cut off the transmission pathway by exterminating lice, rats and fleas, and at the same time, actively treating the pathogenesis as well as taking appropriate symptomatic treatment [8].

General treatment

Bed rest, supply enough heat, maintain water and electrolyte balance.

Early isolation, early treatment, good nursing care to prevent complications [2,9].

Pathogenic treatment

Pathogenic treatment is the most important therapeutic measure, which requires the selection of appropriate drugs under the guidance of doctors.

Mostly choose doxycycline, dimethylamine tetracycline (minocycline), usually 12 to 24 hours after taking the drug the condition is significantly improved.

Symptomatic treatment

When persistent high fever is present, ibuprofen and acetaminophen may be given.

Plasma supplementation, low molecular dextrose, etc. may be considered for those who show signs of hypotension and are considered hypovolemic.

Prognosis

Cure.

Prognosis depends on many factors, including the patient’s age, the presence of complications, and the presence of prompt and effective treatment.