Typhus Fevers

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—bacterial infections cause both. The bacteria are small and very difficult to cultivate. Originally, they were thought to be viruses. The disease occurs after bacteria (Rickettsia) transfer 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.

There is some confusion surrounding the term "typhus." Many people equate typhus with typhoid (typhoid fever), which is incorrect. There is confusion for multiple reasons. Both diseases have in common the symptom of high fever, and the major species of Rickettsia that causes endemic typhus is still termed "typhi." However, the causes, transmission, pathology, and treatment of these diseases are quite different. Salmonella species cause typhoid fever, and this is unrelated to Rickettsia.

Additionally confusing is the term scrub typhus, which refers to a related but different disease caused by the cellular parasite Orientia tsutsugamushi. This disease is related to typhus and endemic to South America and some parts of Africa but is caused by a different genus and species of bacteria and is transmitted by a different vector (mites). 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.

• 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, crowded human living conditions) with the more pathogenic R. prowazekii. Epidemic typhus has a milder form termed Brill-Zinsser disease, which occurs when R. prowazekii bacteria reactivate in a person previously infected with epidemic typhus.

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.

Typhus is sometimes generally labeled as flea-borne typhus, tick-borne typhus, or louse-borne typhus, depending on the vector that transmits the bacteria. They are difficult to cultivate because they usually only grow within the 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 species responsible for the two main types of typhus are Rickettsia 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 (Ctenocephalides felis), has been linked to people with endemic typhus also.

• Epidemic typhus usually spreads to humans from body lice (Figure 1) feces contaminated with R. prowazekii or occasionally from animal droppings contaminated with these bacteria.
• Endemic typhus usually spreads to humans by flea feces or animal droppings containing R. typhi or R. felis. The flea or louse (Pediculus humanus) 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 of rickettsiae can occur if infected fleas or lice 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.

Fig. 1: Photo of a body louse and larvae; SOURCE: World Health Organization

Typhus risk factors include living in or visiting areas where the disease is endemic. These include many port cities where rat populations are high and areas where trash accumulates and hygiene may be low. Disaster zones, homeless camps, poverty-stricken areas, and other similar situations that allow rodents to come into close contact with people represent the greatest threats.

These are the same type of conditions that lead to outbreaks of cholera, tuberculosis, and viral diseases like influenza. Spring and summer months are when fleas (and ticks) are most active, but infections can occur any time of the year.

Symptoms of endemic typhus develop within about one to two weeks after the initial infection and may include a high fever (about 105 F), headache, malaise, nausea, vomiting, and diarrhea. A petechial rash on the chest and abdomen typically begins about 4-7 days after the initial symptoms above develop, and the rash often spreads.

Some patients may also have a cough and abdominal pain, joint pain, and back pain. Symptoms may last for about 2 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 for 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 be life-threatening.

Medical professionals base their diagnosis on the patient's clinical history, physical exam, and tests based on the identification of the bacterial genus and species by PCR testing of a skin biopsy from skin rash or lesions, or blood samples. Immunohistological staining can identify the bacteria within infected tissue (skin tissue, usually).

Typhus can also be diagnosed, usually late or after the disease has been treated with antibiotics when significant titers of anti-rickettsial antibodies are detected by immunological techniques. Although some state labs may do these tests, healthcare professionals should contact the CDC 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.

Physicians recommend antibiotic therapy 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.

Early diagnosis and appropriate treatment yield an excellent prognosis for almost all patients with any of the types of typhus. Delayed, 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 of 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 worsen the prognosis in endemic and epidemic typhus to fair or poor are renal insufficiencies, pneumonia, and central nervous system problems.

Efforts to prevent typhus have been successful when people are able to avoid contact with the vectors that spread typhus (mainly fleas and lice) or fecal droppings from rodents. In areas where endemic typhus exists, or in outbreaks of epidemic typhus, efforts to treat domestic animals to rid them of fleas are good preventive measures.

Many experts suggest that good sanitation, flea-control measures, and reducing populations of rats, mice, and other animals that may carry the bacteria and their vectors are effective. Use insect repellents and insecticides (for example, 1% malathion or 1% permethrin) if fleas and lice reside in the local environment. If the problem is lice and boiling clothing is not an option, avoiding any physical contact with infested clothing for 5 days will allow the lice to die because they need a blood meal in less than 5 days to survive.

Currently, there is no commercially available vaccine for endemic or epidemic typhus. The CDC does not recommend taking any antibiotics to prevent the disease.

One of the first written descriptions of the disease (probably of epidemic typhus) describing rash, sores, delirium, and about 17,000 deaths of Spanish troops was during the siege of Granada in 1489. Further descriptions over time termed the disease gaol or jail fever. In 1759, English authorities estimated about 25% of all prisoners in England died of jail fever per year. In 1760, the disease was named typhus, from the Greek smoke or stupor because of the symptom of delirium that can develop. Many typhus epidemics raged throughout Europe for several centuries and were often related to poor living conditions brought about by wars. For example, some historians estimate more of Napoleon's troops were killed by typhus than by Russian soldiers during their retreat from Moscow in 1812. Ireland and the Americas recorded several epidemics. In the 1830s, over 100,000 Irish died from outbreaks. In the U.S. between 1837 and 1873, outbreaks were recorded in Philadelphia, Concord, Baltimore, and Washington, D.C.

Henrique da Rocha Lima, a Brazilian doctor, discovered the cause of epidemic typhus in 1916 while doing research on typhus in Germany. However, over 3 million deaths were attributed to typhus during and after World War I. Delousing stations were frequently set up to try to reduce the rate of typhus infection and death among troops and civilians. Even though a typhus vaccine was developed before World War II, typhus epidemics continued, especially in German concentration camps during the Holocaust (Anne Frank died in a camp at age 15 from typhus). Eventually, DDT was used to kill lice at the end of World War II and only a few epidemics (in Africa, the Middle East, Eastern Europe, and Asia) have occurred since then. Because of toxicity, DDT has been banned in the U.S. since 1972.

Endemic typhus seems to be increasing or perhaps is being recognized and correctly diagnosed more often in the U.S. An example is the following: Although endemic typhus is usually found in cooler environments, in 2011, Travis County, Texas, (including Austin, Texas) was declared to be endemic for murine (endemic) typhus with 53 cases diagnosed. California also has endemic typhus. In 2018, Galveston County, Texas, reported 17 individuals with the disease—the first time it was diagnosed was in 2012. Authorities suggest many more people may be infected but have not been diagnosed.