Bacteria

What is Epidemic Typhus: History, Symptoms, Diagnosis, Treatment, Prevention, and More

Author Chandana Balasubramanian , 31-Mar-2022

Epidemic typhus is caused by the bacteria Rickettsia prowazekii and is spread through body lice, Pediculus humanus humanus. The word typhus is from ‘tûphos,’ a Greek word that means a fever, heavy stupor, or delirium because of its symptoms. While it is considered rare in modern times, the disease has killed more people than all the wars in history [1], [2]. 

 

Public health agencies need to stay vigilant against potential outbreaks because R.prowazekii can be used as a bioterrorism agent. The bacteria are small, have a low infectious dose, result in high morbidity and mortality rates, and require enhanced diagnostic and disease surveillance methods to track outbreaks. They are classified as a category B bioterrorism agent (the second-highest priority) by the Centers for Disease Control and Prevention (CDC), and a tier 1 select agent because of the potential threat to public health [3] [4].  

 

What makes epidemic typhus so deadly? Why does it spread so fast? How did typhus, one of the biggest killers, end up becoming a rare disease? 

 

The story of typhus covers centuries of sickness and devastation across continents. It involves the gripping story of subterfuge and sabotage of the Nazis by scientists and researchers in World War II. The story continues in ongoing surveillance to protect the world from widespread devastation due to outbreaks of bioterrorism.

How it is Spread

 

Humans are the main reservoir for the bacteria, however, it has been detected in livestock and some wild animals. In the United States, the flying squirrel, Glaucomys volans, has been discovered to be a reservoir. This type of epidemic typhus, spread by flying squirrels is known as sylvatic epidemic typhus or sylvatic typhus [5]. 

 

People at risk of contracting epidemic typhus are those who live in overcrowded and unsanitary conditions, like war zones, refugee camps, detention centers, and prisons. The disease is more common during the winters when people do not change their clothes as often as they do during warmer weather. These conditions are more likely to trigger a body louse outbreak which leads to Brill-Zinsser disease, and eventually a typhus outbreak. Medical professionals and other healthcare workers who treat these infected individuals also face a high risk of infection [2]. 

Brill-Zinsser, a milder form of epidemic typhus, is a recurrent or delayed version. Brill-Zinsser occurs when the Rickettsia prowazekii bacteria enters a human host and stays latent for months or even years. The bacteria then reactivates and causes symptoms similar to the original attack. It then spreads through the feces of the body lice and can lead to a typhus outbreak [6].

History of Epidemics and Outbreaks

 

The disease is named ‘epidemic typhus’ due to the large-scale epidemics it caused in war zones and regions affected by natural disasters – the term is almost synonymous with the majority of wars throughout history. While the disease was well-described in 1498 during the Granada War. Scholars even suspect that it may have caused the Plague of Athens in 430 BC, a devastating epidemic that killed almost a quarter of the population [7]! 

 

It caused large-scale devastation during the Napoleonic Wars, in Ireland in the early 1800s, and during The Great Irish Famine in the late 1840s. Irish refugees fleeing the famine brought epidemic typhus over to the North American continent. Over 20,000 people, mostly Irish immigrants, in Canada died from the disease during the North American Typhus epidemic of 1847. The United States experienced its first epidemic in 1837 in the city of Philadelphia [8]. 

 

In the 20th century, epidemic louse-borne typhus was the biggest cause of death during World War I. Three million soldiers died in Russia and millions more in countries like Poland and Romania. By World War II, the development of an effective vaccine protected many soldiers. However, millions of prisoners in German Nazi concentration camps like Auschwitz, including Anne Frank, died from epidemic typhus due to the unhygienic conditions and a lack of vaccines [9], [10]. 

 

Nowadays, epidemic typhus cases are sporadic and found in the cooler mountainous regions of Asia, Africa, and South America. Burundi, Ethiopia, and Uganda have reported the largest number of cases since World War II [11]. 

 

The disease is also known by many other names, including epidemic typhus fever, camp fever, jail fever, gaol fever, war fever, red louse disease, ship fever, and more. 

 

While rare, typhus has not been completely eradicated. Sporadic outbreaks continue to occur.

 

Who Discovered Epidemic Typhus?  

 

Research work on epidemic typhus fever was fraught with the high risk of contracting the disease. 

 

Charles-Jules-Henri Nicolle, a French physician, was the first to demonstrate that typhus could be transmitted from one person to another by body lice. In 1928, he was awarded the Nobel Prize in Physiology or Medicine for this discovery. During his work, he was infected with the disease and survived [2],[8]. 

 

Many others who worked with R. prowazekii, however, succumbed to the infection. For example, Howard T. Ricketts, a researcher from the United States, became infected and died during his work on typhus in Mexico. In Europe, a Czech scientist called Stanislaus von Prowazek died from an epidemic typhus infection during research [2]. 

 

In 1916, Henrique da Rocha Lima, a Brazilian researcher who worked with Prowazek, continued the work on typhus and identified the bacteria as the pathogen causing epidemic typhus. He also introduced “Rickettsia” as a new class of microbes and named it after his colleagues Ricketts and Prowazek in honor of their work [12].

 

No story about typhus is complete without the accomplishments and fascinating story of Robert Weigl, a Polish zoologist. In 1920, Weigl created the first typhus vaccine. His success attracted the attention of many world leaders, including Adolf Hitler who allowed Weigl’s lab to flourish even as he invaded Poland. Weigl hired thousands of scientists, immunologists, mathematicians, and more to work in his lab and protect them from being sent to concentration camps or put to death. Weigl and his team smuggled the real vaccines into polish ghettos as part of the Polish resistance, and gallons of a weakened version to the Germans, saving the lives of many [9],[13]. 

 

The development of the vaccine and the efforts of Robert Weigl, Hélène Sparrow, and numerous others helped drastically reduce the incidence and prevalence of epidemic typhus [13],[19]. 

Pathogenicity and Life Cycle

 

The rickettsia family of bacteria is unique. They are obligate, intracellular, gram-negative coccobacillus parasites and constitute a separate group of bacteria. This is because they can be spread by fleas, ticks, body lice, and other such arthropods. Diseases caused by different varieties of Rickettsial bacteria are grouped together and known as Rickettsial diseases. These include typhus and spotted fever [2],[14].  

 

Body lice that are infected by the Rickettsia prowazekii bacteria are only vectors, not reservoirs. They turn red and die within five to six days of getting infected. At first, the bacteria multiply in the gut of the louse. The gut then detaches, ruptures, and releases the rickettsia bacteria into the feces [2],[6].

 

A human can get infected if the infected feces come in contact with a bite site or a cut on the skin. It is important to note that the bite of an infected louse does not spread the disease to humans; the infected feces do. Humans may also inhale dried, infected lice feces through the air. Body lice that feed on the blood of a person infected with epidemic typhus can become infected, and the cycle continues [15].

Epidemic Typhus Symptoms

 

The incubation period for epidemic typhus is 10 – 14 days after exposure. 

 

Epidemic typhus symptoms include: 

  • High fever of 105 – 106 ℉ that can last up to two weeks 
  • Chills 
  • Headache
  • Muscle pain (myalgia)
  • Hallucinations
  • A dry cough
  • Fatigue
  • Vomiting
  • Sensitivity to light

 

Some individuals develop a red rash on the back, chest, and stomach that may then spread to other parts of the body [2][15]. 

 

If untreated, the mortality rate for epidemic typhus can be as high as 60% with the highest at-risk patients being elderly and malnourished patients [16]. 

Diagnosing Typhus

 

The most common diagnostic method is a serology (blood) test to detect IgG or IgM antibodies. The bacteria can also be detected through a smear or tissue culture tests of skin lesions and nucleic acid amplification (PCR) [11],[15]. 

 

The symptoms of epidemic typhus fever are similar to several other medical conditions like dengue, malaria, brucellosis, and more. This makes diagnosis challenging. Epidemic typhus must also not be confused with endemic typhus (also known as murine typhus). 

 

Endemic typhus is caused by the bacteria Rickettsia typhi and is transmitted by mostly fleas. People infected with endemic typhus also present with a high fever, a rash that begins on the trunk of the body and spreads, nausea, vomiting, and includes diarrhea as a symptom [17].  

 

Epidemic typhus has similar symptoms but distinguishing characteristics of malaria and typhoid fever are a lack of splenomegaly, rigors, and diarrhea. While symptoms are similar to endemic typhus, they do not include diarrhea, bleeding into the skin, delirium, and death [2].

 

As a result, early diagnosis relies on knowing if a patient has been in crowded or unhygienic areas, has a persistent fever, or has been in contact with flying squirrels.

Typhus Treatment

 

Epidemic typhus is treated with antibiotics like Doxycycline or Chloramphenicol. This treatment is very effective against the infection, with a 0% mortality rate [15]. Untreated epidemic typhus, however, can have a mortality rate as high as 40 – 60% [16]. Treatment is most effective when early. As a result, treatment does not have to be delayed until laboratory tests return.

Prevention of Typhus

 

Currently, there is no vaccine for typhus. While a typhus vaccine was developed and used in World War II, it was discontinued because of the side effects and the dwindling number of cases worldwide [9]. 

 

Epidemic typhus occurs in crowded, unsanitary locations. The best way to prevent typhus is to improve awareness and hygiene. This includes regular bathing, changing clothes regularly even in winters, dealing with rodents because they may carry arthropods, avoiding travel to regions with unsanitary and unhygienic conditions. If such travel cannot be avoided, tick repellant can be used [15]

References
[1]“Etymologia: Typhus,” Emerg. Infect. Dis., vol. 15, no. 6, p. 977, 2009.
[2]S. M. Akram, M. Ladd, and K. C. King, “Rickettsia Prowazekii,” in StatPearls [Internet], StatPearls Publishing, 2021.
[3]“CDC,” Cdc.gov, 15-May-2019. [Online]. Available: https://emergency.cdc.gov/agent/agentlist-category.asp. [Accessed: 26-Mar-2022].
[4]“DSAT – What is a Select Agent?,” Cdc.gov, 11-Mar-2022. [Online]. Available: https://www.cdc.gov/cpr/dsat/what-is-select-agents.htm. [Accessed: 26-Mar-2022].
[5]A. S. Chapman et al., “Cluster of sylvatic epidemic typhus cases associated with flying squirrels, 2004-2006,” Emerg. Infect. Dis., vol. 15, no. 7, pp. 1005–1011, 2009.
[6]R. Kollipara and S. K. Tyring, “Rickettsial Infections,” in Tropical Dermatology, S. K. Tyring, O. Lupi, and U. R. Hengge, Eds. Elsevier, 2017, pp. 280–296.
[7]B. A. Cunha, “The cause of the plague of Athens: plague, typhoid, typhus, smallpox, or measles?,” Infect. Dis. Clin. North Am., vol. 18, no. 1, pp. 29–43, 2004.
[8]E. Angelakis, Y. Bechah, and D. Raoult, “The history of epidemic typhus,” Microbiol. Spectr., vol. 4, no. 4, 2016.
[9]A. Polak, K. Pawlikowska-Łagód, A. Zagaja, and A. Grzybowski, “Typhus works of Rudolf Weigl, PhD, Ludwik Fleck, MD, and Eugeniusz Łazowski, MD, against the Nazis,” Clin. Dermatol., 2022.
[10]“Anne Frank’s last months,” Anne Frank Website, 31-Mar-2015. [Online]. Available: https://www.annefrank.org/en/about-us/news-and-press/news/2015/3/31/anne-franks-last-months/. [Accessed: 26-Mar-2022].
[11]G. Informatics, “GIDEON (Global Infectious Diseases Epidemiology Online Network),” GIDEON database.
[12]F. Bernardes Filho and J. C. R. Avelleira, “Henrique da Rocha Lima,” An. Bras. Dermatol., vol. 90, no. 3, pp. 363–366, 2015.
[13]A. Allen, The fantastic laboratory of Dr. Weigl: How two brave scientists battled typhus and sabotaged the Nazis. New York, NY: WW Norton, 2015.
[14]D. H. Walker, “Rickettsiae,” in Medical Microbiology. 4th edition, University of Texas Medical Branch at Galveston, 1996.
[15]CDC, “Epidemic Typhus,” Centers for Disease Control and Prevention, 09-Feb-2021. [Online]. Available: https://www.cdc.gov/typhus/epidemic/index.html. [Accessed: 26-Mar-2022].
[16]Y. Bechah, C. Capo, J.-L. Mege, and D. Raoult, “Epidemic typhus,” Lancet Infect. Dis., vol. 8, no. 7, pp. 417–426, 2008.
[17]CDC, “Flea-borne (murine) typhus,” Centers for Disease Control and Prevention, 09-Feb-2021. [Online]. Available: https://www.cdc.gov/typhus/murine/index.html. [Accessed: 26-Mar-2022].
[18]N. Baumslag and E. Shuster(reviewed), Murderous medicine: Nazi doctors, human experimentation, and Typhus, vol. 115. Westport, Connecticut, USA: Praeger Publishers, 2005.
[19]J. Lindenmann, “Women scientists in typhus research during the first half of the twentieth century,” Gesnerus, vol. 62, no. 3–4, pp. 257–272, 2005.
Author
Chandana Balasubramanian

Chandana Balasubramanian is an experienced healthcare executive who writes on the intersection of healthcare and technology. She is the President of Global Insight Advisory Network, and has a Masters degree in Biomedical Engineering from the University of Wisconsin-Madison, USA.

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