Symptoms And Progression Of Bubonic Plague In Humans

  • Poppy Sophia Clarke Bachelors of Science (Hons), Infectious Diseases (Biomedical Sciences), The University of Edinburgh
  • Farah Hamdan M.Sc. in Infection Biology, M.Sc. in Clinical Laboratory, B.S. in Pharmacy and Pharmaceutical Chemistry, Tishreen University
  • Karan Yadav BSc in Neuroscience, University of Leicester

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Introduction

The bubonic plague is a deadly infectious disease that caused an infamous pandemic during the 14th century, leading to nearly 25 million deaths worldwide.4,1 This major historical event is known as the “Black Death”. The bubonic plague is caused by the bacterium Yersinia pestis, which can be transmitted from fleas to humans and from human to human once progresses to pneumonic plague. In modern times, with antibiotics, the plague can be prevented from causing serious illness if caught early enough. This article will discuss the characteristics and symptoms of both pneumonic and bubonic forms of the plague in humans and explore the importance of education and awareness of the disease.

Cause and transmission

The bubonic plague is an infectious disease that affects the lymphatic system and is caused by the bacterium Yersinia pestis. It is transmitted to humans through bites  or direct contact with an infected flea or rodent. 

The bacteria enter the human body and travel to the lymph nodes located in areas such as the groin, neck, and axillary regions (armpits)14, 2 Here, the bacteria multiply, causing the lymph nodes to enlarge and swell. These swollen lymph nodes are called buboes and are typically the size and shape of a chicken egg.

Advanced progression of the disease can affect the lungs and lead to pneumonic plague, the only form that can be transmitted from human to human through inhalation of respiratory droplets containing Yersinia pestis or via direct contact. 

Signs and symptoms 

Early symptoms

Early symptoms of bubonic plague start to occur around two to six days after infection. These include symptoms15,3 that can be characteristic of many infections:

  • High Fever
  • Headache
  • Nausea
  • Vomiting
  • Diarrhoea
  • Stomach and joint aches
  • Fatigue

The key symptom for identification is the presence of buboes, often on the neck or armpit region.

Progression of the disease

Advanced symptoms

The bubonic plague requires urgent medical treatment, especially when advanced symptoms begin to present. The major symptom is the development of buboes (swollen lymph nodes). If the infection is not treated once buboes have developed, the bacteria may progress into two other, more severe forms of the disease.4 

If Yersinia pestis enters the bloodstream, it can result in septicemia (also known as sepsis) and develop into septicemic plague. Conversely, if the bacterium reaches and infects the lungs, it can lead to pneumonic plague. These are both severe and life-threatening progressions from the bubonic plague that can be differentiated based14,2 on the location and nature of the infection, as represented in Table 1.

Table 1: Bubonic vs Septicemic vs Pneumonic plague (bacterium: Yersinia Pestis)

Disease ProgressionBubonic PlagueSepticemic PlaguePneumonic Plague
Area of InfectionLymph NodesBloodstreamLungs
Symptoms15,3- Fever and chills
- Nausea and vomiting
- Diarrhea
- Fatigue and muscle aches
- Abdominal pain
- ShockInternal bleeding
- Skin bleeding (skin turns dark/dies)
- Shortness of Breath
- Chest PainBloody mucus
- Watery Mucus
DevelopmentTransmission from infected animal or humanYersinia Pestis progression from lymph node to bloodstream infection
Bubonic plague progression to infection of the lungs.
Transmisionflea-animal-humanflea-animal-humanhuman-human
Severity level6,5(severe)30-60% Fatality (if untreated)(severe)30-100% Fatality(if untreated)(most severe)100% Fatality(if untreated)

Diagnosis and Detection

Early diagnosis of the plague is crucial due to the rapid developmental nature of Yersinia pestis. Early detection can help minimise poor health outcomes that may be deadly and prevent the progression of the bacterial infection to septicemic or pneumonic plague. 

Testing is required to diagnose the plague and can be done by growing the bacteria from blood cultures, samples of pus (thick, white-yellowish fluid) from buboes, or testing blood from a suspected infected patient.6 An individual can also be tested using a rapid diagnostic test (RDT), such as a dipstick test, which can give results in about 15 minutes. This is a useful and widely used diagnostic method, particularly in low-resource settings where access to hospital and laboratory diagnostics may be limited. These rapid diagnostic tests 7 detect a specific part of the bacteria, allowing the infected individual to isolate and prevent the spread of the plague to others if a positive result is detected.

Treatment and management

Yersinia pestis is a bacterium that  can be treated with antibiotics; prompt treatment is crucial because untreated bubonic plague can result in increased fatality rates. The most common antibiotics used to treat bubonic plague are streptomycin and gentamicin, which must be administered intravenously (inserted through the vein). If these first-line antibiotics are unavailable, doxycycline can be used.8 

It is important to use antibiotics as urgently as possible because the longer the disease has to spread, the lower the success rate of the treatment. Patients undergoing treatment must be in strict isolation in a hospital to prevent human-to-human transmission. Additionally, the infected individual may require respiratory support if the infection affects their ability to breathe.9  

Summary of management steps:

Step 1: Recognise Symptoms

Step 2: Diagnostic testing and isolation

Step 3: Treatment via antibiotics and isolation

Step 4: After symptoms and infection are clear, exit isolation

Prevention of outbreaks

A key factor in the prevention of bubonic plague is awareness and education about the infectious disease. It is important for people to be aware of any risks in their area of catching the bubonic plague and to recognise its symptoms. This knowledge allows individuals to be more cautious about flea bites, reduce their exposure by avoiding handling rodents, and take isolation precautions if they believe they have been in contact with someone who may have pneumonic plague.

Public health measures to manage bubonic plague outbreaks involve various efforts. One focus area is identifying and stopping the source of infection, which includes killing rodents likely vectors for the bubonic plague to prevent zoonotic (animal-to-human) transmission. Another measure involves providing training and protective equipment for healthcare workers, particularly in infectious disease wards, to prevent human-to-human transmission. Additionally, appropriate healthcare, such as administering intravenous antibiotics and maintaining isolation until symptoms and infection have cleared, is crucial.5

Current status of bubonic plague

The bubonic plague still exists around the world. Although the production of antibiotics means Yersinia Pestis is  treatable, treatment is timely, and if not caught and treated urgently, then can progress into a deadly disease. 

In Madagascar 202110 a pneumonic plague epidemic occurred, which consisted of 19 confirmed cases of human pneumonic plague and three confirmed cases of human bubonic plague. Eight out of 22 individuals died, which shows that even with antibiotics, the rapid progression and action of this infectious disease still comes with a high death rate. In this case, over 1000 close contacts of these 22 were contacted and received precautionary treatment to prevent the spread and development of bubonic and pneumonic plague. This emphasises the importance of awareness, surveillance, and prevention of Yersinia pestis as it is still a prevalent infectious disease that does result in death even with the introduction of antibiotics.

Future threats associated with yersinia pestis 

As discussed, Yersinia Pestis can cause a deadly infectious disease if left untreated. No effective vaccine against it is yet available. This is an area for concern as the development of antibiotic resistance from overuse of first-line antibiotics such as streptomycin and doxycycline threatens the treatment and maintenance of bubonic plague. Although these antibiotics still prove to be effective in early caught bubonic plague cases, the potential for resistance has been identified in some strains of Yersinia Pestis by the identification of resistance genes.11 There is also the threat of increased global warming which has the potential to lead to a rise of the bacterium in rodents.12 A final threat includes the use of Yersinia Pestis as a weapon for biological warfare,13 which could have serious effects on public health and the prevalence of disease.

Summary

The bubonic plague is a life-threatening and deadly infectious disease. Buboes are a key sign of bacterial infection by Yersinia pestis, and medical advice should be sought immediately upon recognising signs and symptoms of the bubonic plague infection. The timing of treatment is crucial to reducing the fatality rate of the infected individual, and early detection can save lives. Prompt treatment can also prevent the progression to more severe forms of the disease, such as pneumonic plague, which can spread via human-to-human transmission. Thus, the bubonic plague is a serious public health concern because even with the introduction of antibiotics, the disease continues to cause deaths to this day. Hence, preventative measures such as isolation, identifying the source of the disease, and managing infected individuals are essential for controlling and reducing the prevalence of the bubonic plague.

References

  1. Riedel S. Plague: From Natural Disease to Bioterrorism. Proc (Bayl Univ Med Cent). 2005;18(2):116–24. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200711/
  2. Ligon BL. Plague: A Review of its History and Potential as a Biological Weapon. Semin Pediatr Infect Dis. 2006;17(3):161–70. Available from: https://www.sciencedirect.com/science/article/pii/S1045187006000513
  3. Ditchburn JL, Hodgkins R. Yersinia pestis, a problem of the past and a re-emerging threat. Biosafety and Health . 2019;1(2):65–70. Available from: http://sciencedirect.com/science/article/pii/s2590053619300230
  4. Howard J. Plague (Black Death) Bacterial Infection Information and Facts [Internet]. National Geographic. National Geographic; 2020. Available from: https://www.nationalgeographic.com/science/article/the-plague
  5. World Health Organization. Plague - Madagascar [Internet]. www.who.int. 2021. Available from: https://www.who.int/emergencies/disease-outbreak-news/item/plague---madagascar
  6. World Health Organization. Plague [Internet]. World Health Organization. World Health  oOrganization; 2022. Available from: https://www.who.int/news-room/fact-sheets/detail/plague
  7. Sebbane F, Lemaître N. Antibiotic Therapy of Plague: A Review. Biomolecules. 2021;11(5):724. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151713/
  8. Danis D, Cramer C, Christensen B. Pneumonic plague in a 15-year-old Utah girl. J Emerg Nurs. 1995;21(6):491–3. Available from: https://pubmed.ncbi.nlm.nih.gov/8709455/
  9. Chanteau S, Rahalison L, Ratsitorahina M, Mahafaly null, Rasolomaharo M, Boisier P, et al. Early diagnosis of bubonic plague using F1 antigen capture ELISA assay and rapid immunogold dipstick. International journal of medical microbiology: Int J Med Microbiol. . 2000;290(3):279–83. Available from: https://pubmed.ncbi.nlm.nih.gov/10959730/
  10. Nikiforov VV, Gao H, Zhou L, Anisimov A. Plague: Clinics, Diagnosis and Treatment. Advances in Experimental Medicine and Biology. 2016;293–312.
  11. Nikiforov VV, Gao H, Zhou L, Anisimov A. Plague: Clinics, Diagnosis and Treatment. Advances in Experimental Medicine and Biology. 2016;293–312.
  12. Riehm JM, Rahalison L, Scholz HC, Thoma BR, Pfeffer M, Léa Mamiharisoa Razanakoto, et al. Detection of Yersinia pestis using real-time PCR in patients with suspected bubonic plague. Molecular and Cellular Probes. 2011;25(1):8–12.Available from:https://pubmed.ncbi.nlm.nih.gov/20933595/ 
  13. Butler T. Plague into the 21st Century. Clinical Infectious Diseases [Internet]. 2009 Sep [cited 2019 Apr 10];49(5):736–42. Available from: https://academic.oup.com/cid/article/49/5/736/308284
  14. CDC. CDC | Facts About Plague [Internet]. emergency.cdc.gov. 2019. Available from: https://emergency.cdc.gov/agent/plague/factsheet.asp
  15. CDC. Signs and Symptoms of Plague [Internet]. Plague. 2024 [cited 2024 May 16]. Available from: https://www.cdc.gov/plague/signs-symptoms/index.html

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