Clinical Overview of Epidemic Typhus

Background

Outbreaks of epidemic typhus are most often associated with the clustering of large populations in situations with limited access to hygienic services, such as those resulting from war or famine, or occurring in refugee camps, prisons, and among persons experiencing homelessness in association with exposure to body lice. However, isolated cases have also been reported in recent years outside of such settings, typically in association with flying squirrels.

The primary vector of epidemic typhus is Pediculus humanus corporis (human body louse). People become infected with Rickettsia prowazekii when they come into contact with the feces or crushed bodies of infected lice on cut or abraded skin. Inhalational exposure of dried louse feces has been reported. R. prowazekii can remain infective in louse feces for up to 100 days. Body lice can proliferate rapidly and spread from person to person through contaminated bedding and clothes. These lice infestations can lead to outbreaks of disease in populations with crowding, such as refugee camps.

In the United States, cases of epidemic typhus have been associated with exposure to flying squirrels or their nests. Fleas and lice carried by the squirrels become naturally infected with R. prowazekii; however, the exact mechanism of transmission to humans remains unknown.

Clinical characteristics

Signs and symptoms of epidemic typhus usually appear abruptly, 8–16 days following exposure to infected lice. Illness can vary from mild to severe, and can be fatal. Symptoms of acute R. prowazekii infection are generally non-specific and include:

• Fever and chills
• Headache
• Altered mental status
• Rapid breathing
• Cough
• Myalgia
• Rash
• Nausea
• Vomiting

Delay in treatment with doxycycline may lead to progression of the disease, including neurologic manifestations such as confusion, seizures, or coma, and widespread vasculitis. These symptoms are due to damage to the vascular endothelial cells throughout small blood vessels. Laboratory abnormalities of acute infection may include elevated bilirubin, elevated hepatic transaminases, and thrombocytopenia. Flying squirrel-associated typhus cases are generally less severe, and no fatal cases have been reported.

Rash

The rash usually begins 2-3 days after the onset of symptoms. It typically begins as a maculopapular eruption on the trunk and spreads to the extremities, usually sparing the palms of hands and soles of feet. When the disease is severe, petechiae may develop. The rash may be variable among individuals and stage of infection, or may be absent altogether. The presence or morphology of a rash should NOT be relied upon for diagnosis.

Brill-Zinsser Disease

Recrudescent infection with R. prowazekii, called Brill-Zinsser disease, may occur months or years after the initial illness, most often during times of extreme stress or when the immune system is impared. Brill-Zinsser disease is seen in patients who were not treated during their initial infection. The symptoms of Brill-Zinsser disease are similar to those of primary infection, with a rapid onset of chills, fever, headache, and malaise. However, Brill-Zinsser disease is generally milder and is rarely fatal. Patients with Brill-Zinsser disease harbor active R. prowazekii and therefore may pose a risk for reintroduction of the organism and new outbreaks.

Brill-Zinsser disease is not known to occur following infection with other rickettsial pathogens.

Clinical diagnosis

Diagnosis is based on clinical findings and epidemiologic factors, as diagnostic tests are not reliable early in the illness course. Epidemic typhus should be considered in patients with persistent fever, a history of body louse exposure in congregate or other crowded settings, or persons who may have come in contact with flying squirrels or their nests. When treated early, patients may experience a less severe illness and shorter recovery time.

Treatment should never be withheld pending results of diagnostic testing. Epidemic typhus has the potential to spread rapidly among persons living in close quarters, and precautions should be taken to rapidly identify and treat patients and to eliminate body louse infestations.

Clinicians who suspect epidemic typhus should notify their state public health department immediately.

Laboratory confirmation

R. prowazekii can be detected via indirect fluorescent antibody (IFA) test, immunohistochemistry (IHC), polymerase chain reaction (PCR) assay of blood, plasma, or tissue samples, or culture isolation. Serologic tests are the most common means of confirmation and can be used to detect either IgG or IgM antibodies.

Diagnosis is typically confirmed by documenting a four-fold rise in antibody titer between acute and convalescent samples. Acute specimens are taken during the first week of illness and convalescent samples are taken 2–10 weeks later. Detectable levels of IgG or IgM antibodies generally do not appear until 7–10 days after the onset of illness.

Because IgG antibody titers may persist in some individuals for years after the original exposure, only demonstration of recent changes in titers between paired specimens can be considered reliable serological confirmation of an acute epidemic typhus infection. R. prowazekii antigens may cross react with those of R. typhi, and occasionally with R. rickettsii. Persons with Brill-Zinsser disease generally show a rise in IgG but not IgM antibodies to R. prowazekii.

IHC can be used to detect infection with typhus group Rickettsia (including R. prowazekii and R. typhi) in formalin-fixed tissue samples. PCR of whole blood or tissue can distinguish between infection with R. typhi and R. prowazekii although the sensitivity of these assays vary considerably based on the sample type, timing of sample collection, and the severity of disease. Since epidemic typhus is not common in the United States, testing is not typically available at state and local health departments. Serologic and molecular tests can be performed at the CDC, through submission from state health departments.

Treatment

Doxycycline is the treatment of choice for suspected cases of acute epidemic typhus and Brill-Zinsser disease in adults and children of all ages.

Recommended dosages of doxycycline:

• Adults over 45 kg (100 lbs): 100 mg twice per day
• Children under 45 kg (100 lbs): 2.2 mg/kg body weight (max dose 100mg) twice per day

Patients should be treated for at least 3 days after the fever subsides and until there is evidence of clinical improvement (usually a minimum of 7–10 days).

Treatment of acute infection with doxycycline may prevent the subsequent development of Brill-Zinsser disease, but definitive data are lacking. Patients with body louse infestations should be treated with delousing gels or creams (pediculicide).