Background

Plague is an acute, highly contagious and highly fatal infectious disease caused by Yersinia pestis, it is a vector-borne disease prevalent among wild rodents [1]. Under certain conditions, it can be transmitted to humans through flea bites and other routes, leading to the occurrence of plague [2]. Once it occurs and spreads, it can easily become a major public health emergency. The most recent plague pandemic was the “Surat storm” in India in 1994 [3]. In China, it is classified as the first Class A communicable disease under the “Law on the Prevention and Control of Infectious Diseases”. According to the World Health Organization(WHO), there were 3,248 cases of plague worldwide from 2010 to 2015, resulting in 584 deaths. According to data from the Chinese Center for Disease Control and Prevention(CDC), there has been no widespread plague in China in the past four years, with only a few sporadic cases, mainly in Inner Mongolia and Ningxia. In 2019, there were 5 reported cases of plague with 1 death. In 2020, there were 4 reported cases with 3 deaths. In 2021 and 2022, there was 1 reported case of plague each year. This article reports a case of pneumonic plague in Xizang, China, in 2023, which is a rare occurrence.

Case presentation

A 37-year-old male herdsman was admitted to the People’s Hospital of Cuona County on September 19, 2023, due to cough, phlegm and lisp for 3 days accompanied by fever for 2 days. On examination, his body temperature was 38.5 °C, and respiratory rate was 46 breaths per minute. He experienced difficulty breathing and generalized fatigue. Chest computed tomography (CT) revealed diffuse nodules and patchy consolidations in both lungs, as shown in Fig. 1A-C. CT findings suggested both lung infection, and oral ibuprofen suspension was administered at that time. The next day (September 20, 2023), he was observed for further treatment. The patient had a body temperature of 40.5 °C, rapid breathing, significant cough with bloody sputum, cyanotic lips, and cold extremities.Coarse breath sounds and moist rales were audible on both sides. Blood routine examination showed that white blood cell count (WBC) and platelet decreased, electrolyte disturbance (Table 1). A follow-up chest CT showed significant progression of diffuse nodules and patchy consolidations compared to the previous day’s images, as shown in Fig. 1D-F. Specific details can be seen in Fig. 2, where diffuse central nodules in the pulmonary lobes, secondary lobular consolidation with a gravity-dependent distribution, and air bronchogram were observed, consistent with pulmonary hemorrhage changes. The patient was clinically diagnosed with severe pneumonia. Continuous oxygen inhalation, electrocardiogram monitoring, antibiotics (piperacillin sulbactam sodium 3 g was administered intravenously every 8 h) and cooling treatment were given. At 1 a.m. on September 21, the patient developed unconscious, unresponsive, and had no palpable carotid artery pulse. Despite resuscitation efforts, the patient could not be revived and was pronounced clinically dead. Epidemiological tracing found that there were dead marmots in the patient’s residence. The patient was clinically highly suspected of plague infection and immediately sent to the Xizang Autonomous Region CDC. The results of autopsy showed that the lung tissue was swollen and congested with a dark purple color, and there was no adhesion between the lung tissue and the chest wall. There were multiple hemorrhagic spots of varying sizes on the surface of one lung lobe, dark red exudate on the lung section, and bloody effusion in the pleural cavity. Yersinia pestis was isolated and cultured from the autopsy specimens. Based on the clinical presentation and autopsy results, the F1 antigen test was positive, so the patient was finally diagnosed with pneumonic plague.

Fig. 1
figure 1

Comparison of two CT scans. The patient is male, 37 years old, herdsman. On September 19, 2023, CT in Fig. 1A-C showed diffuse nodules, ground glass and solid shadow in both lungs. On September 20, 2023, CT in Fig. 1D-F corresponding to the CT level of Fig. 1A-C showed a significant increase in the number of lesions and an enlarged scope, suggesting acute exacerbation of the lesions in the short term

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Table 1 The patient’s laboratory indicators details
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Fig. 2
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Detailed analysis of CT scan on September 20, 2023. CT in Fig. 2A-G showed multiple lobular core nodules in both lungs (as shown by black arrows in Fig. 2A-B), and secondary lobular distribution lesions were shown by red arrows in Fig. 2A-C. The air bronchial sign, as shown in Fig. 2D, showed smooth and natural bronchial shape, and no necrosis or cavity was found in the consolidation. In Fig. 2D-E, the blue arrow showed the falling interlobar fissure, indicating the trend of gravity distribution of the lesion and indicating obvious exudation of the lesion. Figure 2F showed obvious lesions in the low-hanging position of the both lungs, further indicating the trend of gravity distribution of the lesions. The mediastinal window in Fig. 2G showed a typical air bronchial sign. In summary, the imaging diagnosis is consistent with the changes in alveolar hemorrhage

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Discussion and conclusions

Plague, also known as the “Black Death”, is a severe infectious disease caused by the gram-negative bacterium Yersinia pestis [2]. It has erupted many times in history and is typically classified into three types: bubonic plague, pneumonic plague, and septicemic plague [4]. By consulting pubmed and web of science databases, the literature from 2020 to 2023 were reviewed worldwide (Table 2) [1, 4,5,6,7,8], we learned that bubonic plague is the most common type, which is mainly characterized by lymph node swelling and paining. Pneumonic plague is the most deadly type and primarily spreads through the respiratory tract. Within 24–36 h of onset, patient may experience difficulty breathing, coughing, coughing up large amounts of frothy pink or bright red blood, chest pain. The paucity of pulmonary signs are often disproportionate to the severity of systemic symptoms. Septicemic plague is the rarest but most severe type and can lead to septic shock and multiple organ failure [5, 9, 10]. The patient in this article had acute onset, mainly manifested as cough, hemoptysis and dyspnea, accompanied by varying degrees of high fever, without palpable lymph node enlargement, which are the typical presentations of pneumonic plague. The main route of transmission for plague is through intermediary hosts such as rodents or fleas [11], and it can also spread through human-to-human contact, especially in cases of pneumonic plague (Fig. 3). Our patient in this article was herdsman who had not left the local area since June 2023. Dead marmots were found in the patient’s residence, but the family denied peeling them. It is inferred that the patient may have been infected through flea bites, but the possibility of being infected by contact with dead marmot cannot be ruled out.

Table 2 Cases of plague described in the literature worldwide(2020–2023)
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Fig. 3
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Hand-drawn picture of the plague transmission route. A: rodents carrying Yersinia pestis infect humans through direct contact; B and C: fleas infect humans through bites after absorbing the blood of infected animals; D: humans carrying Yersinia pestis infect other people through respiratory transmission

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After the invasion of Yersinia pestis into the human body, it primarily affects the lymphoid tissue, causing acute swelling, bleeding, and necrosis of the lymph nodes, forming visible gray-white necrotic foci [12]. A large number of neutrophils and monocytes can be seen infiltrating the lymph nodes. If Yersinia pestis further invades the entire lymphatic system, it can lead to severe systemic infection [13]. In pneumonic plague, extensive necrosis and hemorrhage occur in the lung tissue, with the alveoli filled with a large amount of exudate and red blood cells [14]. The interstitial tissue and peribronchial tissue may also be affected, leading to varying degrees of inflammation. Increased cell permeability can result in secondary exudative pulmonary edema [12]. Therefore, the pathological changes of pneumonic plague were characterized by alveolar hemorrhage, pulmonary edema, and inflammatory exudative changes. The gold standard for laboratory diagnosis of plague is the isolation and identification of the Yersinia pestis pathogen from clinical specimens [15]. At present, F1 antigen is the typical target antigen for immunological detection of plague [12, 15]. In our case, histological examination showed consolidation of the lung tissue, and Yersinia pestis was isolated. The alveolar wall was hyperemic, edematous and fractured, and there was a large amount of exudate in the alveolar cavity. The pulmonary interstitium were filled with edema, and scattered inflammatory cell infiltration were found. These findings were consistent with previous literature.

The imaging manifestations of plague are rarely reported and are not specific. By reading a large number of literature, we summarized the following: (1) Pulmonary consolidation: patchy, localized, or diffuse consolidation shadows appear in the lungs, with blurred edges that can merge into large areas, and may even show “white lung” changes [16]. The pathological basis of this change is diverse and may be pulmonary hemorrhage, pulmonary edema, or inflammatory exudation. (2) Pleural effusion: pneumonic plague can cause pleural effusion [14]. (3) Lymphadenopathy with necrosis: formation of multiple irregular enlarged lymph nodes with low-density areas inside [6]. (4) Cellulitis: cellulitis is a severe complication of plague, characterized by subcutaneous soft tissue swelling in the affected area, forming multiple high-density honeycomb-like shadows [7]. In our case, CT revealed multiple acinar nodules distributed along the core of the pulmonary lobules in both lungs, with indistinct margins and partial fusion, as well as patchy high-density shadows distributed along the secondary pulmonary lobules, demonstrating air bronchogram sign. The density of the dependent lung zones was higher, and the density near the interlobar fissure in the upper lungs was also relatively high, and the interlobar fissure was sagging, which was a typical gravity distribution, indicating fluid accumulation. All the above manifestations supported the changes consistent with alveolar hemorrhage, which was in line with the pathological features of plague.

In addition to pneumonic plague, which can cause diffuse alveolar hemorrhage, the following diseases need to be distinguished: (1) ANCA-associated vasculitis: this is a connective tissue disease that typically has a chronic course and is positive for ANCA antibodies [17]. Multiple systems are often involved, such as rash and renal impairment. Granulomatosis with polyangiitis can lead to the formation of granulomatous lesions with cavity formation in the lungs. (2) Leptospirosis: the patients usually have a history of contact with infested water, and have an acute onset. The main clinical manifestations are fever, myalgia, fatigue, and conjunctival hyperemia [18]. Imaging findings show diffuse ground-glass opacities in both lungs, with indistinct borders and a predominant peripheral distribution [19]. Thickening of interlobular septa is also observed, indicating diffuse hemorrhagic changes in the lungs. (3) Hantavirus pulmonary syndrome: This is a disease caused by infection with the Hantavirus [20]. Clinical manifestations mainly include fever, shock, and acute renal failure. Imaging manifestations included pulmonary edema, pulmonary hemorrhage, and pleural effusion. The imaging features in our case are consistent with diffuse alveolar hemorrhage and damage. Although these findings lack specificity, they can help clinical exclude other common pathogens such as pyogenic bacterial and mycobacterium tuberculosis.

At present, the primary treatment of plague is the use of antibiotics, and the commonly used drugs are doxycycline and streptomycin [21]. Supportive cares, including rehydration and nutritional support, are also necessary to maintain stable vital signs. In addition, patients should be isolated immediately to prevent transmission to others. Medical staff should strictly follow protective measures when handling patients, dead bodies, or objects that may contain Yersinia pestis.

Plague is one of the most severe infectious disease, which can be divided into many types. The pathological characteristics of pulmonary plague primarily include alveolar damage, alveolar hemorrhage, and pulmonary edema. CT findings may show diffuse nodules, consolidation of secondary pulmonary lobules, gravity-dependent distribution, air bronchogram sign, and pleural effusion. The combination of clinical and imaging can help us to diagnose and treat as soon as possible to save lives. This article aims to raise awareness among tourists visiting regions such as Xizang, Qinghai, Gansu, etc., urging them to stay away from rodents and marmots as a precautionary measure.