Typhus is a disease caused by bacteria (mainly Rickettsia typhi or R. prowazekii). There are two major types of typhus: endemic (or murine typhus) and epidemic typhus. The bacteria are small and very difficult to cultivate; originally they were thought to be viruses. The disease occurs after bacteria (Rickettsia spp.) are transferred to humans usually by vectors such as fleas or lice that have acquired the bacteria from animals such as rats, cats, opossums, raccoons and other animals.


Endemic typhus (mainly caused by R. typhi) is also termed murine typhus and "jail fever". "Endemic typhus" also means that an area or region has an animal population (usually mice, rats, or squirrels) that has members of its population continually infected with R. typhi that through flea vectors can incidentally infect humans.


Epidemic typhus (caused by R. prowazekii) is the more severe form of typhus. It has also been termed recrudescent or sporadic typhus. "Epidemic typhus" also means that a few animals, (usually rats) via lice vectors, can incidentally infect large numbers of humans quickly when certain environmental conditions are present (poor hygiene, poverty, crowded human living conditions) with the more pathogenic R. prowazekii.


Epidemic typhus has a milder form termed Brill-Zinsser disease; it occurs when R. prowazekiibacteria reactivate in a person previously infected with epidemic typhus.


There is some confusion surrounding the term "typhus". Many people occasionally equate typhus with typhoid (typhoid fever). This is incorrect but easily understandable due to the evolving understanding of diseases and the antiquated but stubbornly adhered to terminology by the medical community.


For example, both diseases have in common the symptom of high fever, and the major species of Rickettsia that causes endemic typhus is still termed "typhi", but the causes, transmission and pathology of these diseases are quite different (Salmonella spp. cause typhoid).


Another example is the term "scrub typhus". This disease is related to typhus but is caused by a different genus and species of bacteria and is transmitted by a different vector (see the causes section below). The aim of this article is to inform the reader about the two major worldwide variations of typhus, endemic and the more severe epidemic typhus.


Symptoms of endemic typhus develop within about one to two weeks after initial infection and may include a high fever (about 105 F), headache, malaise, nausea, vomiting, diarrhea and a rash that begins about four to seven days on the chest and abdomen after the initial symptoms above develop; the rash often spreads. Some patients may also have a cough and abdominal, joint, and back pain. Symptoms may last for about two weeks and barring complications or death (less than 2% die), symptoms abate.


However, epidemic typhus symptoms, although initially similar to endemic typhus, become more severe. The rash may cover the entire body except the palms of the hands and the bottoms of the feet. Patients may develop additional symptoms of bleeding into the skin (petechiae), delirium, stupor, hypotension and shock, which can cause their death.


The causes of typhus are small Gram-negative coccobacilli-shaped bacteria, members of the genus Rickettsia that are intracellular parasites of many animals and utilize the components within the cell to survive and multiply. They are difficult to cultivate because they usually only grow within cells they infect.


Occasionally, the bacteria may become dormant in infected cells, and years later, again begin to multiply (causing Brill-Zinsser disease). Generally, typhus follows an animal (rat, mouse) to vector (louse, flea) cycle. Humans are incidentally infected usually when the vectors come in close proximity to humans. The two Rickettsia spp. responsible for the two main types of typhus are R. prowazekii, the cause of epidemic typhus, and R. typhi, the cause of endemic typhus.


However, R. felis, another species usually found in cat and cat fleas, has been linked to people with endemic typhus also. Epidemic typhus is usually spread or transmitted to humans from body lice (Figure 1) feces contaminated with R. prowazekii or occasionally from animal droppings contaminated with these bacteria. Endemic typhus is usually transmitted to humans by flea feces or animal droppings containing R. typhi or R. felis.


The flea or louse bite causes itching and scratching and may allow the bacteria to enter the scratch or bite area in the skin. Indirect person-to-person transmission can occur if lice or fleas infect one person who develops the disease and then the infected lice or fleas move from person to person by direct contact or via shared clothing. In general, head lice that differ from body lice do not transmit Rickettsia.


R. prowazekii, R. typhi, and R. felis differ from other Rickettsia spp. For example, R. rickettsii and many other R. spp. are considered in the medical literature as a separate group of bacteria and are transmitted by ticks, cause Rocky Mountain spotted fever (RMSF), and preferentially infect and spread through endothelial cells after tick bites.


Orientia tsutsugamushi, a bacterial species originally named Rickettsia tsutsugamushi, adds complexity to the typhus terminology because the disease it causes is termed scrub typhus. This change in name of the bacteria occurred because the bacteria were found to be genetically distinct enough to be termed a separate genus named Orientia. Also, scrub typhus is transmitted, in general, by a different vector: mites or "chiggers".


Scrub typhus is found mainly in Asia and Australia. Many investigators consider scrub typhus as a different disease, in terms of the bacterial agent, vector, and localization, that is only remotely related to the two major types of typhus seen worldwide (endemic and epidemic typhus). For additional details about scrub typhus, we refer the reader to the last reference in the additional information section.


There are two other aspects readers may discover about these interesting Rickettsia bacteria. First, recent research has implicated that intracellular structures that produce energy for all animal cells, termed mitochondria, arose from primitive ancestors of Rickettsia bacteria. Genetic studies show that the many DNA sequences in Rickettsia bacteria are more closely related to the DNA sequences found in mitochondria than to DNA found in other bacterial genera.


The other aspect is disturbing because Rickettsia (mainly R. prowazekii) have been studied and found to be possible agents for biological warfare since the bacteria can artificially be spread by aerosol. However, highly skilled personnel and technical expertise is required to develop these organisms into a weapon and, because the diseases caused by these organisms are treatable with antibiotics, some experts suggest that the organisms will not be developed beyond lab experimentation in most countries.


What is the treatment for typhus?


Antibiotic therapy is recommended for both endemic and epidemic typhus infections because early treatment with antibiotics (for example, azithromycin, doxycycline, tetracycline, or chloramphenicol) can cure most people infected with the bacteria. Consultation with an infectious-disease expert is advised especially if epidemic typhus or typhus in pregnant females is diagnosed. Delays in treatment may allow renal, lung, or nervous system problems to develop. Some patients, especially the elderly, may die.


How is typhus diagnosed?


The diagnosis is based on the patient's clinical history, physical exam, and tests based on identification of the bacterial genus and species by PCR testing of skin biopsy of skin rash, skin lesions, or blood samples or by immunohistological staining that identifies the bacteria within infected tissue (skin tissue, usually).


It can also be diagnosed, usually late or after the disease has been treated with antibiotics, when significant titers of antirickettsial antibodies are detected by immunological techniques. Although some state labs may do these tests, the CDC should be contacted for testing questions and be given information if there is an outbreak of epidemic typhus. These tests help distinguish between epidemic and endemic typhus, anthrax, and other viral diseases.


What is the prognosis of typhus?


Early diagnosis and appropriate treatment yield an excellent prognosis for almost all patients with any of the types of typhus. Delayed or undiagnosed or untreated typhus has a less promising prognosis, but the prognosis is related to the type.


For example, untreated endemic typhus has a death rate under 2% of patients, but untreated epidemic typhus has a death rate that ranges from about 10%-60% of infected patients, with those over 60 years of age having the highest death rates. Even if the patient does not die, complications that may reduce the prognosis in endemic and epidemic typhus to fair or poor are renal insufficiency, pneumonia, and central nervous system problems.

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