What Causes Typhus?

Typhoid typhus is an acute infectious disease caused by Rickettsia. Epidemic typhus is caused by Plasmodium rickettsii and is transmitted by body lice, mostly in winter and spring. Endemic typhoid fever is caused by the rickettsial mosquito infection, which is mediated by rats and rat flea, and most of them are in summer and autumn. Endemic people are less ill than epidemic people.

Li Yanzeng

(Attending physician)

Department of Infectious Diseases, Beijing Youan Hospital

Spotty typhus (scrubtyphus) is an acute infectious disease caused by Rickettsiatsutsugamushi. Rodents are the main source of infection. Chigger is used as a vector to transmit typhus to humans. Its clinical features are acute onset, fever, rash, lymphadenopathy, hepatosplenomegaly, and eschar at the bite of chigger mites.

Western Medicine Name: typhus
English name: scrubtyphus
Affiliated Department: Internal Medicine-

The main symptoms: Chill, high fever
Main cause: Rickettsia infection
Contagious: Contagious

Introduction to typhus

Acute infectious disease caused by Rickettsia. It can be divided into epidemic typhus and endemic typhus. The former is also called typhus typhus, an acute infectious disease transmitted by human lice caused by Plasmodium rickettsii, and the latter is also called flea typhus or mouse typhus, which is caused by Molex Acute infectious disease caused by rat flea and transmitted by rat fleas. The incubation period is 5 to 21 days, and most of them are 10 to 12 days. The manifestations are acute onset, chills, high fever, severe headache, muscle pain, and tenderness, especially in the gastrocnemius muscle, flushing of the face, conjunctival congestion of the eyeball, and neurological symptoms such as insomnia, tinnitus, delirium, mania, and even coma. May have a rapid pulse or toxic myocarditis. More than 5 days after the onset of the disease, congestive maculopapular or maculopapular rash appeared throughout the body, which later became hemorrhagic with splenomegaly. The above manifestations of endemic typhus are mild. The diagnosis was based on epidemiological history (the local epidemic, history of lice parasites and bites, etc.) and typical clinical manifestations. Definite diagnosis can be used for serological examinations such as Wai Fei's reaction and rickettsia separation. Tetracycline or chloramphenicol have specific effects. Preventive measures should be taken to prevent lice and rodents.

Typhoid fever includes epidemic typhus and endemic typhus. Epidemic typhus is an acute infectious disease caused by Rickettsia Prowazeki. Although Egypt has isolated Platts from goats, the United States has isolated Platts from flying squirrels. However, there is insufficient evidence for epidemic typhus as a natural epidemic. Epidemic typhus is still a human-lice-to-human transmitted disease. Humans are the sole host and body lice are the vector of transmission. Platts rickettsia grows and reproduces in gastrointestinal epithelial cells of body lice, and is excreted by lice feces. The lice feces contaminate human skin lesions and cause infections. In developed countries, due to their high living standards and good sanitary conditions, they often take baths and change clothes to prevent the growth of body lice. In developing countries, especially among people who breed in clothes lice, they are often endemic. The last epidemic in China was in Zhaotong, Yunnan Province in the late 1970s.

Endemic typhus is a natural epidemic and is caused by Rickettsia Mooseri. Rats are the storage host, Indian rat flea is the vector, and humans are the victims. The cycle was rat-flea-human transmission. However, Qiu Fuxi and others also isolated M. rickettsiae from tropical rat mites. Endemic typhus is worldwide. Wherever there are rats and fleas, the source of endemic typhus may exist. Developed countries report fewer cases. After China's liberation, there were three epidemic peaks: the first was from 1950 to 1952, which was a mixed epidemic and endemic, with Yunnan being the worst. Except for Taiwan, the second epidemic peak occurred in 28 provinces, cities, and autonomous regions. The third epidemic peaked from 1980 to 1984. The incidence rate in China has been decreasing since the early 1980s, and has been rising since 1997.

Classification of typhus

The disease can be divided into epidemic typhus and endemic typhus.

Causes of typhus

The rickettsial typhus is round, oval or short rod-shaped, with a size of (0.3 0.6) m × (0.5 1.5) m. It is negative for Gram stain and purple-red for Giemsa staining. Intracellular parasitic microorganisms. In smear staining microscopy, in the cytoplasm, especially in the cytoplasm of monocytes and macrophages, rickettsia typhus typhus is often clustered on one side of the nucleus. The rickettsial typhus breeds in a dichotomous manner and takes about 8 hours to reproduce. Among a variety of experimental animals, mice are most susceptible, more than 7-9 days after intraperitoneal vaccination, and death on 10-15 days. When mice develop disease or die, rickettsia typhus can be found in smears or prints of tissues and organs such as ascites, mesentery, peritoneum, liver, spleen, and kidney. Among them, peritoneal and mesenteric prints have higher detection rates. In addition, chicken embryo yolk sac inoculation can also be used to isolate the pathogen of typhus. Rickettsia typhus can also parasitize a variety of cultured cells, such as primary rat kidney cells, primary chicken embryo cells, Hela cells, etc. Rickettsia typhus is the weakest type of rickettsia that is pathogenic to humans. It has a tendency to be naturally inactivated and lysed. It is not easy to store at room temperature. It is sensitive to various disinfection methods, such as death in 0.5% phenol solution or heating to 56 . After being left at 37 ° C for 2 hours, the ability to infect cells was significantly reduced. In infected chicken embryos, vigor can be stored for 17 days at 4 ° C and 6 weeks at -20 ° C. In the infected cell suspension, its vitality can be preserved with liquid nitrogen for more than 1 year.

Rickettsia typhus parasitic in cells is extremely sensitive to chloramphenicol, tetracycline and erythromycin, but resistant to penicillin, cephalosporins and aminoglycosides. Rickettsia typhus and Proteus OXK strains are cross-immunogenic. Therefore, clinically available patients' serum can be diluted for Proteus OXK agglutination reaction to assist diagnosis of typhus.

Rickettsia typhus is more prone to genetic mutations, so differences in antigenicity and virulence between strains are more common. Humans can develop specific immunity after being infected with rickettsial typhus, and there is also a certain cross-immunity between different serotypes. According to the different antigenicity, rickettsial typhus can be divided into 12 serotypes, namely Karp, Gilliam, Kato, TA678, TA686, TA716, TA763, THl817, Shimokoshi, Kawasaki, Kuroki and Broyong due to typhus. Rickettsia is more susceptible to genetic mutations, so new serotypes are still being discovered. Because there may be large differences in antigenicity and pathogenicity between different serotypes, different strains, the severity of disease and mortality may also vary greatly. Existing data show that the Gilliam serotype is the main type in mainland China, accounting for about 50%, and the rest are Kato and untyped. Taiwan Province is dominated by Karp, followed by TA716, TA763 and unshaped.

Pathophysiology of typhus

After a person is bitten by an infected lice or flea with rickettsial body, rickettsial typhoid fever multiplies locally, then enters the bloodstream, produces rickettsemia, and then reaches the body Organs and tissues, clinical manifestations of toxemia. Toxin released after the death of Rickettsia typhus is the main cause of disease. Can cause pimples, eschar and ulcers locally. Lymphadenopathy can be caused throughout the body, especially in the scorch area. The central lymph nodes may show necrosis. Yellow-green exudate can be seen in the serous cavity, such as the thoracic cavity, abdominal cavity, and pericardial cavity. The internal organs are generally congested, the spleen is often congested, and the swelling can be 2 to 5 times, and the liver can also be enlarged. Lungs may have hemorrhagic pneumonia or secondary bronchopneumonia. Meningoencephalitis can occur in the brain. The kidneys can present with extensive acute inflammatory lesions. The gastrointestinal tract is often extensively congested.

The histopathological changes of typhus are mainly in the vascular system. Focal or extensive vasculitis and perivascular inflammation can be seen, with lung, brain, heart, and kidney being the most significant. Monocytes, lymphocytes, and plasma cells infiltrate around blood vessels. Edema of vascular endothelial cells and necrosis and rupture of vascular wall can be seen in severe patients. Rickettsia typhus has been detected in vascular endothelial cells, macrophages, and cardiomyocytes in various organs of patients. ^[1]

Clinical manifestations of typhus

(I) Incubation period: The general incubation period for epidemic typhus is 10 to 14 days. If the infection is large, the onset time can be advanced. Prodromal symptoms are not obvious, and some are only low fever, headache and fatigue. The incubation period for endemic typhus is usually 5 to 15 days.

(B) Symptoms and Signs: There are four main symptoms and signs of epidemic and endemic typhus, namely fever, headache, rash and lymphadenopathy.

(3) Physical examination: The most common sign is splenomegaly.

(4) Complications: Otitis media, mumps, bacterial pneumonia are common complications, and some may appear scrotum, penis, labia swelling and gangrene. Sometimes nerve irritation symptoms may occur, some of which are coma, dull, stupid, and excited.

Diagnosis of typhus typhus

One. Auxiliary inspection

See monographs on epidemic typhus and endemic typhus.

two. Differential diagnosis

1. Leptospirosis is also common in endemic areas of typhus. Moreover, both are more common in summer and autumn, and both have fever, conjunctival congestion, and lymphadenopathy, so attention should be paid to identification. Leptospirosis often has gastrocnemius pain, subconjunctival hemorrhage, and early kidney damage without rash, scorch, or ulcers. Serological and etiological examinations can be performed when necessary. Serum Leptospira agglutination and dissolution test is positive.

2. Typhoid fever is more common in the winter and spring seasons and cold areas. It has a history of lice parasites or a bite of rat fleas, fever, maculopapular rash, and skin scorching ulcers and lymphadenopathy. Serum Proteus agglutination was positive for OX19 and negative for OXK.

3. Before the onset of typhoid fever, there is often a history of eating unclean food. Onset is slow, body temperature gradually increases, relatively slow pulse, indifferent expression, bloating, constipation, right lower quadrant tenderness, and roseola are common. The total number of white blood cells decreased, and eosinophils decreased or disappeared. The fatal response can be positive, and blood and bone marrow cultures can have typhoid bacteria growth.

4. Sepsis often has primary infections. Relaxation heat type and irregular heat type are common. Gram-positive bacteria cause skin rashes or pattern changes more often, while Gram-negative bacteria cause shock more often. The total number of white blood cells increased, neutrophils increased, and the nucleus shifted to the left. Outer-Fei reaction is negative, blood and bone marrow culture may have pathogenic bacteria growth.

5. Before the onset of dengue fever, he had lived or stayed in the endemic area of dengue fever, and had a history of biting by Aedes mosquito during the day, more than in summer and autumn. Headache and systemic pain are more pronounced. Spots of maculopapular rash and subcutaneous bleeding are more common. Total white blood cells and platelets are often reduced. Dengue virus can be isolated from the sera of patients with a disease course shorter than 3 days. Anti-dengue virus antibodies were positive in the serum.

6. Epidemic hemorrhagic fever, headache, low back pain and orbital pain are more obvious, shock occurs more frequently when the temperature drops, subcutaneous bleeding points, ecchymosis are common, oliguria or anuria are common. The total number of white blood cells is increased, and atypical lymphocytes often exceed 10%, and platelets are significantly reduced. Blood urea nitrogen and creatinine levels gradually increased with prolonged oliguria or anuria. Serum-specific antibodies against epidemic hemorrhagic fever virus were positive.

7. At the same time, attention should also be paid to the differential diagnosis of influenza, malaria, acute upper respiratory tract inflammation, malignant histiocytosis, and lymphoma.

Typhus fever treatment

Measles typhoid medication

(1) Macrolides: including erythromycin, roxithromycin, azithromycin, clarithromycin, etc., which have a good effect on typhus. The usual dose of erythromycin is 1.2 g / d for adults, 25-30 mg / (kg? D) for children, and it is taken 3 or 4 times a day, or 2 or 3 times by intravenous drip. The commonly used dose of roxithromycin is 300 mg / d for adults, 100 mg / d for children weighing 12 to 23 kg, 200 mg / d for 24 to 40 kg, and the oral dose can be doubled for the first time. Azithromycin, the adult dose is 0.25g, once per day, orally, the first dose can be doubled. The usual dose of clarithromycin is 500 mg for adults, 2 times a day, orally. After fever, it can be changed to 250 mg each time. There were more patients with rapid fever reduction within 24 hours after treatment, and the treatment course was 8-10 days. People with obvious liver damage should not use macrolides.

(2) Tetracyclines: including tetracycline, doxycycline, minocycline, etc., also have good curative effect on typhus. The usual dose of tetracycline is 2 g / d for adults, 25-40 mg / (kg? D) for children, and it is taken orally in 4 times. The usual dose of doxycycline is 0.2 g / d for adults and 4 mg / (kg? D) for children. Take it once or twice daily. The first dose can be doubled. The usual dose of minocycline is 0.2g / d for adults and 4mg / (kg? D) for children. Take it once or twice a day. The first dose can be doubled. The course of treatment was 8 to 10 days. Tetracyclines should not be used in children under 8 years, pregnant women and lactating women.

(3) Chloramphenicol: Chloramphenicol has a good effect on typhus. The usual dose is 2 g / d for adults and 25-40 mg / (kg? D) for children. The daily dose can be administered by intravenous drip or divided into 4 oral administrations. Patients have rapid fever reduction within 24 hours after administration. The dose is halved after fever reduction, and continued to be used for 7 to 10 days to avoid recurrence. Because chloramphenicol can induce aplastic anemia, it should not be used as the preferred treatment for typhus. Chloramphenicol should not be used in young children, pregnant women and lactating women.

(4) Quinolones: ofloxacin, ciprofloxacin, pefloxacin, fleroxacin, lomefloxacin, enoxacin ), Sparfloxacin (spara), etc. Often used are ofloxacin and ciprofloxacin. Ofloxacin has an adult dose of 0.2 g / time, 2 times / day, and can be taken once daily on the first day. The adult dose of ciprofloxacin is 0.25g / time, 2 times / day, and it can be taken once a day on the first day. Intravenous infusion can be used if necessary, and the course of treatment is 8-10 days. Quinolone should not be used in children under 8 years, pregnant women and lactating women.

Among the above-mentioned four types of antibacterial drugs, macrolides, tetracyclines and chloramphenicol have a strong anti-killing effect on rickettsia typhus, and the temperature of the patients returns to normal after more than 24 hours of administration. The use of quinolone treatment can also reduce the patient's body temperature to normal within 24 to 48 hours. Usually only one antibacterial agent is needed, and no combined treatment is required. There are data showing that rifampicin is also effective for typhus.

The earlier the diagnosis and treatment of typhus patients, the better the effect. However, when the course of typhus entered the second week, the clinical manifestations became significantly worse, with multiple organ dysfunction and obvious bleeding tendency. When the course of the disease enters the third week, in addition to the obvious exacerbation of the disease, the efficacy of antibacterial treatment is also poor, and the patient's body temperature usually takes 3 to 5 days to gradually decrease to normal.

For children and pregnant patients, macrolides should be selected for pathogen treatment, such as azithromycin and roxithromycin. It is worth pointing out that penicillins, such as ampicillin, cephalosporins, such as ceftazidime, etc., cephalosporins, such as cefoxitin, etc., carbapenems, such as Antibiotics such as imipenem, monocyclic -lactams, such as aztreonam, and aminoglycosides, such as amikacin, have no therapeutic effect on typhus. Because rickettsial typhus is an obligate intracellular parasitic microorganism, and these antibiotics are difficult to enter the cells to play their role, these antibiotics have no therapeutic effect on typhus. Recurrence can occur in a small number of patients. Scorch no longer appears on relapse, and treatment with the same antimicrobials as the first episode is equally effective. ^[2]

Other treatments for typhus

Symptomatic treatment: A variety of complications and comorbidities can occur in typical and severe patients, and appropriate symptomatic treatment measures should be taken in time to improve the treatment effect.

Typhus disease prevention

1. Controlling the source of infection is mainly rodent control. The masses should be mobilized, and comprehensive measures should be adopted to use various mousetraps in combination with drugs to kill rats. Commonly used rodenticides are zinc phosphide, Antu, and enemy rats.

2. Cut off the transmission route to prevent being bitten by chigger mite larvae. Avoid lying on the grass and drying clothes in the onset season. When working in endemic areas, you must tighten your cuffs and trousers, and apply insect repellents such as diphenyl phthalate or benzyl benzoate.

3. Improving the population's resistance to disease There is no typhus vaccine available for the population. Preliminary studies have shown that the epidermal protein antigen with a molecular weight of 56 × 103 in Rickettsia typhus is highly immunogenic. The gene encoding the protein has been successfully expressed in E. coli, and whether it can be used as a vaccine remains to be further studied.

Care for typhus

Onset of typhus is often mistaken for a cold. If the patient has a fever for a long time, and he / she has been sitting or lying in the wild grasses or touching crops with tapeworms in recent weeks, he should pay attention to whether the lymph nodes are swollen and painful and whether there is eschar. Visit the hospital in time to confirm the diagnosis early. Typhoid fever is treated with specific drugs, and the cure rate of early treatment is 100%. Due to the effects of rodent and chigger mite breeding, the epidemic of typhus has obvious seasonal and regional epidemics, and cases usually start in May. The onset season is more common in July-November, and the period from June to September is At peak, there are usually more farmers, and any crops that sit or lie in the epidemic area casually or come in contact with tapeworms can be infected. Humans are generally susceptible to Rickettsia typhus. Farmers, adolescents who have frequent contact with grassland, and workers in the field are prone to typhus. There are more males than females. After illness, they have lasting immunity to the same pathogen, and immunity to different strains can only be maintained for several months.

Rickettsia typhus can also be isolated from chigger mites and rodents in cold regions and high altitudes (above 2500m). Typhoid typhus in China mainly occurs in the provinces along the southeast coast and southwestern regions such as Guangdong, Guangxi, Fujian, Taiwan, Zhejiang, Yunnan, Sichuan, Hainan, Xisha Islands, etc., and also in Hunan, Guizhou, Shandong, Jiangxi, Inner Mongolia, Tibet, Xinjiang and other places. Reports of positive serum immune responses in cases or populations. However, in general, the incidence of typhus has been declining in China. Typhoid fever is also prevalent in Japan, Southeast Asia, islands in the Western Pacific and Indian Oceans, and southeast of the former Soviet Union.

Typhus complications

The more common complications are toxic hepatitis, bronchopneumonia, myocarditis, meningoencephalitis, and acute renal failure. Prognosis: If timely diagnosis and treatment can be made, most patients have a good prognosis. If there are complications, the prognosis is poor. Case-fatality rates vary from 1% to 50%. The case fatality rate is not only related to the differences in the virulence of R. typhi typhi, but also to the duration of the disease. After entering the course of disease 3 to 4 weeks, patients often have obvious multiple organ dysfunction, and patients may die due to multiple organ failure or major pulmonary and gastrointestinal bleeding.

Expert opinion on typhus

Typhoid typhus is mainly transmitted by lice, fleas and chigger mites, and is closely related to environmental and personal hygiene conditions. With the improvement of the global health environment, the incidence of these diseases has decreased year by year, and the case fatality rate has also decreased significantly. Rarely reported deaths in recent years However, for those working in high-risk working groups such as the diagnosis and treatment of infectious diseases, animal research, feeding and experimental research, it is still necessary to understand and master the disease. Once unfortunately encountered, early detection, early isolation and early treatment can be done to reduce damage. ^[3]