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

Epidemic typhus, also known as louse-borne typhus or typical typhus, is an acute infectious disease caused by rickettsia prowazekii transmitted mostly by body lice. The clinical manifestations are persistent high fever, headache, petechiae or maculopapular rash, and involvement of central nervous system, persisting for about 2 - 3 weeks. The disease can relapse in months or years, which is known as recurrent typhus, also known as Brill-Zinsser disease.


Causes

The pathogen is rickettssia prowazekii, which is not significantly different from other rickettsiae in morphology, but is polymorphic in the development in lice intestines. The pathogen is Gram-negative and usually parasitic in vascular endothelial cells of humans and intestinal epithelial cells of body lice, and can also attach to red blood cells and platelets during rickettsemia. The chemical composition and metabolites of the pathogen include proteins, sugars, fats, phospholipids, DNA, RNA, endotoxin-like substances, and various enzymes. The cell wall is similar to that of Gram-negative bacilli.

The pathogens are very sensitive to heat, ultraviolet rays, and general chemical disinfectants, and can be killed at 56 °C for 30 minutes or 37 °C for 5 - 7 hours. They have a strong tolerance to low temperature and dryness, can be survive for several months to years at below -30 °C, and can be active for several months in dried lice feces. Pathogens can grow in tissue culture, especially in chicken yolk sac. Almost pure pathogens can be obtained by injecting infected tissue or secretions into the intestine of lice.

Epidemiology

Source of infection

Patients are the major source of infection. Patients are contagious from last 1 - 2 days of the incubation period to several days after fever drops. The entire communicable period is about 3 weeks, but the infectivity is the strongest in the first week. Pathogens can be latent in the mononuclear phagocyte system for a long time in some patients, and proliferate when the immunity of hosts is relatively reduced, leading to recurrences.

In addition to humans, flying squirrels are also reservoir hosts for rickettssia prowazekii. These flying squirrels live in the eastern and central United States. The transmission between the flying squirrels can be lice or fleas, but the modes to infect humans is not clear.

Modes of transmission

Body lice are the main vector for transmission of pathogens, and head lice and pubic lice can also be vectors. Ticks transmit mainly rickettssia prowazekii in animals.

Susceptibility

All humans are susceptible to the disease, and symptoms in children aged under 15 years are mild if infected. A quite lasting immunity can be acquired after infection, and relapses are less common in a short term.

Pathogenesis

The pathogenesis of this disease is mainly vascular lesions caused by pathogens, and septicemia and some immune and allergic reactions caused by toxins produced by the pathogens. After invasion of the skin and mucous membranes, the pathogens grow and replicate in endothelial cells of regional lymph nodes, small blood vessels, or capillary vessels, causing cell rupture and shedding of pathogens, resulting in primary rickettsemia. Subsequently, pathogens invade more endothelial cells of small blood vessels and capillary vessels, leading to new focal infections. Numerous replication and death of the pathogens cause toxins, resulting in septicemia. Immune and allergic reactions that occur in the second week exacerbate vascular lesions.


Signs and Symptoms

Typical typhus

The incubation period is 5 - 21 days, averagely 10 - 12 days. Few patients have 2 - 3 days of prodromal symptoms, such as fatigue, headaches, dizziness, chills, and low fever. Rapid onset, chills, severe and persistent headaches, muscle pain, and conjunctival and facial congestion are present in most patients.

Fever

The body temperature reaches its peak (39 - 40 °C or higher) on the 2nd to 4th days. Continuous fever in the first week and remittent fever in the second week are present. The duration of fever is usually 14 - 18 days, and then the body temperature quickly returns to normal within 2 - 4 days. Remittent fever and irregular fever are more common, which may be related to the application of antibacterial drugs.

Skin lesions

Rashes are seen in more than 80% of patients, which is an important sign of the disease. The rashes occur 4 - 6 days after onset, initially on the chest, back, armpits, and the upper extremes, quickly spreading to the whole body within one day. There is usually no rash on the face and few rashes on the lower extremities. The skin lesions are round or oval, about 2 - 4 mm in diameter, blanching, initially bright red maculopapular rashes, progressing into dark red petechiae, subsiding in 5 - 7 days, leaving brownish yellow spots or desquamation. Petechiae can persist for 1 - 2 weeks.

Nervous system symptoms

Nervous system symptoms are obvious and occur very early, including fear, excitement, severe headaches, mental retardation, delirium, occasionally meningeal irritation, muscular and lingual tremor, coma, incontinence, difficulty swallowing, and hearing loss.

Cardiovascular symptoms

The increase in heart rate is generally proportional to the increase in body temperature, and cantering rhythm and arrhythmia may occur when toxic myocarditis is present. Shock, hypotension, dehydration, microcirculatory disorders, and cardiovascular and adrenal hypofunction may occur.

Other symptoms

Other symptoms include cough, chest pain, tachypnea, nausea, vomiting, anorexia, constipation, abdominal distension, occasionally jaundice, cyanosis, renal hypofunction, mild spleen enlargement, and hepatomegaly in some patients.

Mild typhus

Mild thypus is manifested by:

  • Short duration of fever (8 - 9 days) and low fever (about 39 °C)
  • Mild septicemia, obvious pain throughout the body
  • Congestive maculopapular rashes on the chest and abdomen, no rash in some patients
  • Mild symptoms of the nervous system, short duration, mainly headaches and excitement
  • Less common hepatosplenomegaly

Recurrent typhus

Recurrent typhus is characterized by:

  • Mild septicemia and mild symptoms of central nervous system
  • Remittent fever for 7 - 11 days
  • No rash or only few maculopapular rashes
  • Sporadicity, no seasonal differences, high incidence in old adults

Histopathology

The basic lesions are small vasculitis, and the typical lesions are proliferative, thrombotic, necrotizing vasculitis, peripheral inflammatory cell infiltration, and rickettsial granuloma. Pathological changes are dermal focal hyalinosis and necrosis, endothelial proliferation in the tunica intima of small arteries and precapillaries, microthrombus formation, rickettsia in endothelial cells, and perivascular lymphocytes, plasma cells, and histocytes infiltration.


Diagnosis

The disease is often endemic, so a history of living or travelling in the endemic area is usually the most helpful for diagnosis.
 
The most effective detection methods for rickettssia prowazekii are indirect immunofluorescence assay (IFA) and polymerase chain reaction (PCR) tests. Culture is difficult and has no clinical significance. For rickettsia spp. detection, PCR is the best method. Serological tests have little significance in the diagnosis of acute infections and usually have a positive result only in the recovery period.


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.


Prognosis

Epidemic typhus rarely causes death in children <10 years of age, but the mortality rate will increase while aging, and in patients > 50 years of age, the mortality rate can reach 60% if untreated.

There is generally no death in recurrent typhus.


Prevention

Delousing and immunization are the most effective preventive measures. Delousing with malathion or lindane for the infected patients can be performed.