| disease | Plague |
| alias | Patient No. 1, Plague |
Plague is a severe pestilence primarily transmitted by the plague bacillus through rat fleas, and it is a natural focal disease widely prevalent among wild rodents. Clinically, it manifests as fever, severe toxemia symptoms, swollen lymph nodes, pneumonia, and a tendency to hemorrhage. Plague has caused several major pandemics throughout world history, resulting in tens of millions of deaths. Before liberation, China also experienced multiple outbreaks with extremely high mortality rates. In 1992, human plague cases were reported in nine countries worldwide: Brazil, China, Madagascar, Mongolia, Myanmar, Peru, the United States, Vietnam, and Zaire, totaling 1,582 cases. Most cases were concentrated in Africa, with a mortality rate of 8.7%. In China, there were 29 cases, mainly in Xishuangbanna. Confirmed plague foci in China are distributed across 17 provinces (autonomous regions) and 216 counties, with ongoing animal plague. Human plague cases expanded from two provinces (Qinghai and Tibet) in 1985 to six provinces, including Yunnan, Inner Mongolia, Xinjiang, and Gansu. In 1994, neighboring India reported an outbreak of 693 plague cases. The prevention and control of plague remain critically important in China.
bubble_chart Epidemiology
(1) Source of Pestilence: The primary sources are rodents and other wild rodents, with the genus Spermophilus and Marmota being particularly significant. It is transmitted by rat fleas. Patients with pneumonic plague are sources of human-to-human transmission of pestilence.
(2) Transmission Route: Before a human plague epidemic, there is usually an epidemic among rats, typically spreading from wild rats to domestic rats. After domestic rats die, rat fleas seek new hosts. After a flea sucks the blood of an infected rat, the pathogen multiplies extensively in the flea's foregut, causing blockage. When an infected flea bites a human, it not only spreads feces containing the pathogen on the skin but also introduces infected blood clots into the human body through regurgitation. Occasionally, the pathogen in flea feces can be rubbed into wounds, infecting humans. When a person crushes a flea, the pathogen inside the flea can also enter the body through wounds. This "rat-flea-human" route is the primary mode of transmission for bubonic plague.
Bubonic plague can complicate into septicemia, leading to pneumonic plague. The plague bacilli in the patient's sputum can be transmitted through droplets or aerosols in a "human-to-human" manner, causing a large-scale epidemic of human plague. Additionally, direct contact with the patient's sputum, pus, or the skin, blood, and meat of infected animals, inhaling contaminated dust, chewing fleas, or consuming undercooked wild rodents can also lead to infection. Recent studies have found the possibility of transmission by ticks.(3) Susceptible Population: Humans are generally susceptible to plague. Vaccination reduces susceptibility, and there is lasting immunity after recovery.
The epidemic season is related to rodent activity (Spermophilus and Marmota can carry the bacteria during hibernation) and flea reproduction. In the south, it often starts in spring and ends in summer, while in the north, it usually begins in summer and autumn and extends into winter. Pneumonic plague is more common in winter.
The plague bacillus belongs to the Enterobacteriaceae family, Yersinia genus, and is a polymorphic, Gram-negative, facultative aerobic bacterium. Its optimal growth temperature is 28°C, and it grows slowly on ordinary culture media, requiring more than 72 hours of cultivation.
There are 17 types of plague bacilli in our country, all named after regions, such as the Qilian Mountain type and the Eastern Tianshan Mountain type.
The antigenic structure of this bacterium is complex, with 18 antigens identified, namely A～K, N, O, Q, R, S, T, and W, among which F1, T, and W are the most important, being specific antigens. F1 is a capsular membrane antigen, which can be used for diagnosis; 131
T antigen is a murine toxin, present within the cells and released upon cell lysis, being the substance responsible for pathogenicity and lethality. The V/W antigen allows the bacteria to maintain virulence within phagocytic cells, resisting phagocytosis. The T antigen has exotoxin properties, acting on the vascular and lymphatic endothelial systems, causing inflammation, necrosis, and hemorrhage.Other virulence factors include pesticin, fibrinolysin, coagulase, and lipopolysaccharide internal toxin.
The plague bacillus can survive in pus, sputum, flea feces, and soil for 10～20 days and 6 months to over 1 year, respectively. The bacteria can be killed by boiling for 1～2 minutes, at 55°C for 15 minutes, or by sunlight exposure for 4～5 hours. 5% lysol or carbolic acid, 0.1%～0.2% mercuric chloride can kill the pathogenic bacteria in sputum within 20 minutes.
The bacteria are transmitted by flea bites, and the bacteria are engulfed by monocytes in the draining lymph nodes but are not killed and can multiply, forming a capsule containing protein I and other toxic substances. The lymph nodes then undergo hemorrhagic necrosis, and the bacteria can spread along the blood circulation and lymphatic vessels, affecting superficial lymph nodes as well as mediastinal and hilar lymph nodes.
10% to 20% of patients develop multilobar pneumonia, which can manifest as lobar consolidation and hemorrhagic necrosis, abscesses. Inhalation of contaminated dust primarily causes pulmonary lesions, but it can also only affect the tonsils and cervical lymph nodes. If not treated promptly, all types of plague can progress to sepsis and involve organs such as the liver and spleen, as well as other lymph nodes.
The basic pathological changes are acute hemorrhage and necrosis of blood vessels and lymphatic vessels, with hemorrhagic inflammation and coagulative necrosis in local lymph nodes, containing a large number of pathogens, and adjacent lymph nodes may also be affected. Pulmonary congestion and edema are present, with occasional scattered necrotic nodules caused by bacterial emboli. The trachea and bronchial mucosa are highly congested, and the lumens are filled with a large amount of bacterial-laden foamy bloody and serous exudate. All organs are congested, edematous, or necrotic. The blood is mostly black, and the serous cavities often contain bloody exudate.bubble_chart Clinical Manifestations
The incubation period is 2-3 days, which can be extended to 9-12 days after vaccination. Clinically, it mostly manifests as glandular, pulmonary, and secondary septicemic types. In recent years, mild and latent infections have also been quite common. The mild type only presents with irregular low-grade fever, mild systemic symptoms, grade I swelling and tenderness of local lymph nodes, and no bleeding; this type is more common in the early or late stages of an epidemic or in vaccinated individuals. Except for the mild type, other types have an acute onset, with severe toxemia symptoms and bleeding phenomena.
(1) Glandular plague is the most common, mostly occurring in the initial stage [first stage] of an epidemic. The lymph nodes enlarge on the first day of the course, accompanied by redness, swelling, and pain, reaching a peak on days 2-4. The inguinal lymph nodes are most frequently involved, followed by the axillary, cervical, and submandibular lymph nodes, usually unilateral but occasionally bilateral, with multiple sites appearing simultaneously. The swollen lymph nodes may suppurate and ulcerate or gradually dissipate, with slow healing of the ulcerated wounds.
Most patients who are not treated in time experience worsening conditions after lymph node enlargement and die within 3-5 days due to severe toxemia, shock, secondary septicemia, or pneumonia. If they survive for a week, the chances of recovery increase.
(2) Pulmonary plague is more common during the peak of an epidemic. Patients have significant toxemia, developing cough, shortness of breath, cyanosis, etc., within 24-36 hours, followed by notable chest pain. Initially, the sputum is scant, later becoming thin and copious, bright red and frothy, containing a large number of pathogens. Dyspnea and cyanosis worsen, but only scattered rales or pleural friction sounds are heard in the lungs, so the symptoms and signs are very disproportionate. Patients may die within 2-3 days due to shock, heart failure, etc. Before death, the patient's entire skin becomes highly cyanotic, hence the name "Black Death."
(3) Septicemic plague can be primary or secondary. The condition of primary cases is critical, caused by weak human resistance and strong pathogenicity, high bacterial load, etc. Systemic toxemia symptoms, central nervous system symptoms, and bleeding phenomena are extremely severe, with excessively high or low body temperature. Patients experience delirium or unconsciousness, and develop shock or heart failure, often dying within a few hours to 2-3 days if treatment is inadequate.
(4) Other rare types include, in addition to the mild type as described above, cutaneous plague, ocular plague, tonsillar plague, intestinal plague, meningeal plague, etc., which will not be detailed here.
The course of each type of plague is generally about 1 week.
bubble_chart Auxiliary Examination
The total white blood cell count and neutrophil count are increased, with anemia being mild grade II, depending on the extent of bleeding. The stool in intestinal plague appears bloody or mucoid bloody.
Collect blood (including heart blood from the deceased), pus, sputum, cerebrospinal fluid, lymph node puncture fluid, and organs (including bone marrow) from the deceased and animals for smear preparation and culture. After staining the smears with various stains (including fluorescent antibody staining), examine them under a microscope. Perform smear tests, phage lysis tests, hemagglutination tests, and animal inoculation on suspicious colonies, following strict protocols and isolation facilities.
Serological tests commonly use the reverse hemagglutination test to detect F1 antibodies. A fourfold increase in antibody titer in serum samples taken two weeks apart during the acute phase is diagnostically significant. A single titer of ≥1:100 also has diagnostic value. Other detection methods include indirect hemagglutination tests, ELISA, and radioimmunoassay.
Based on epidemiological data and some specific clinical manifestations, a diagnosis can generally be made. Mild cases need to be differentiated from acute lymphadenitis, scrub typhus, leptospirosis, and rabbit Rebing, mainly relying on bacteriological examination.
bubble_chart Treatment Measures
(1) Patient Isolation Patients should be isolated in a separate building, and the ward area should be free of rats and fleas. Patients must undergo thorough flea extermination and shower before admission. Patients with pneumonic plague should be isolated in individual rooms. Isolation should continue until symptoms disappear, with blood or local secretion cultures conducted once every 3 days, and three consecutive negative results; for pneumonic plague, sputum cultures should be conducted once every 3 days, with six consecutive negative results before discharge.
(2) General and Symptomatic Treatment During the acute phase, patients should be kept in absolute bed rest, provided with liquid or semi-liquid diets and sufficient fluids, and intravenous rehydration as needed. For dysphoria, restlessness, and local lymph node pain, sedatives and analgesics should be administered. Oxygen should be provided for those with difficulty breathing, and appropriate measures should be taken for shock, DIC, heart failure, etc. (refer to Section 51, "Infectious Shock"). Short-term use of adrenal corticosteroids, such as 100-300mg hydrocortisone intravenously, may be considered for patients with severe toxemia, but must be used in conjunction with effective antibacterial drugs.
(3) Local Treatment Swollen lymph nodes can be treated with topical antibacterial drugs, with 0.5g of streptomycin injected into the surrounding tissue. For those that have softened, incision and pus expulsion can be performed, preferably after more than 24 hours of sufficient antibacterial drug use. Tetracycline or chloramphenicol eye drops can be used for ocular plague. Skin plague can be treated with antibacterial solution wet compresses, rinsing, or topical antibacterial ointment.
(4) Antibacterial Treatment Early and sufficient administration via injection is crucial, though oral administration may be used for mild cases. The initial dose should be large, and the duration of treatment varies depending on the type of illness, continuing for 4-5 days after fever subsides.
Aminoglycosides are the most effective, preferably administered intravenously in the early stages.
Gentamicin for adults is 160-320mg daily, administered in divided doses intravenously, with a treatment course of 7-10 days. Streptomycin is suitable for milder cases such as bubonic plague, with adults receiving 2g daily intramuscularly, divided into 2-4 doses, reduced to 1g daily after fever subsides, with the same treatment course. Pneumonic plague cases require larger doses, such as an initial dose of 160mg gentamicin, followed by 80mg every 6 hours intravenously; streptomycin initial dose of 1g, followed by 0.5g every 4 hours, reduced to 0.5g every 6 hours after fever subsides, for 5-7 days. If aminoglycosides are used in combination with tetracycline or chloramphenicol, the dose may be adjusted accordingly. Kanamycin is less commonly used, with adults receiving 1-2g daily. Aminoglycosides may occasionally cause a Herxheimer-type reaction.
Tetracycline and chloramphenicol should be used in larger doses in the first two days, with adults receiving 3-4g daily, divided into 4 oral doses. If oral administration is not possible, switch to intravenous administration, but the daily dose of tetracycline should not exceed 2g; switch back to oral administration after fever subsides, 1.5-2.0g daily, continued for 6 days.
Sulfonamides are suitable for mild cases and bubonic plague, commonly using SD, with an initial dose of 2-4g, followed by 1-2g every 4 hours, taken with an equal amount of sodium bicarbonate; switch to intravenous administration if oral administration is not possible, and discontinue 3-5 days after body temperature normalizes. Dipyridamole (containing SD400mg, TMP50mg) or compound formula SMZ can also be used, 2 tablets 3-4 times daily, reduced to 2 times daily after fever subsides.
For pneumonic plague, septicemic plague, etc., combination therapy is preferred, with the first choice being streptomycin plus chloramphenicol or tetracycline, and the second choice being gentamicin plus chloramphenicol or tetracycline. Early and sufficient administration is key to success. Anti-plague serum is now rarely used.
In the past, the case fatality rate of plague ranged from 20% to 70%. After the application of antibacterial drugs, the case fatality rate has dropped to about 5%. Patients with pneumonic, septicemic, and meningeal plague almost invariably died without specific treatment, but with early and aggressive intervention, they can often be saved.
Individuals engaged in high-risk occupations in endemic areas and laboratory workers exposed to plague bacilli should consider using formaldehyde-inactivated whole-cell vaccines, with revaccination every 6 months. Short-term travelers to epidemic areas can take tetracycline or compound formula SMZ for prevention. Suspected cases of pneumonic plague should be placed under respiratory isolation, while bubonic plague only requires thorough handwashing for prevention. Those in contact with pneumonic plague patients can take tetracycline 250mg, four times daily. Individuals with respiratory symptoms or fever should undergo medical observation.
Plague in forest rodents can spread to urban rats, posing a long-term threat. Prevention depends on controlling urban rat populations and managing their excreta, as well as monitoring wildlife and their predators. Avoid contact with sick animals and their carcasses, and use flea repellents. Currently, there are no feasible measures to eradicate plague in wildlife. In endemic areas, reducing rodent habitats in residential environments is crucial. Before using rodenticides around homes, insect control should be prioritized to prevent fleas from the animals from biting humans or livestock.
