RARE DISEASE
Plague
Plague
Plague
Synonyms: Y. pestis infection, Yersinia pestis infection
Synonyms: Y. pestis infection, Yersinia pestis infection
Synonyms: Y. pestis infection, Yersinia pestis infection
Drug discovery
3
drugs
With orphan designations
Overview
Plague is a zoonotic disease caused by Yersinia pestis, transmitted through flea bites, contact with infected animals, or inhalation of respiratory droplets. It manifests as bubonic (lymphadenopathy), septicemic (systemic infection), or pneumonic (respiratory) forms, with pneumonic plague being highly contagious and fatal within 18–24 hours if untreated. Rapid diagnosis (antigen tests, culture) and early antibiotic therapy are critical, alongside strict infection control measures for pneumonic cases [1][6][18].
Burden
Case-fatality rate: 7–17% with treatment, but approaches 100% for untreated pneumonic plague [1][4][16].
Major outbreaks occur in resource-limited settings, with ~21,725 cases and 1,612 deaths reported globally from 2000–2009 [4].
Reemergence risks include antimicrobial resistance and climate-driven rodent-flea proliferation [8][18].
Categories: rare infectious diseases
Research Papers
1,025 drug discovery papers about Plague, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,025 drug discovery papers about Plague, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-17 | The 1820 Mallorca plague was not a classic bubonic outbreak.
The 1820 plague outbreak in eastern Mallorca-long treated as a local episode and traditionally classified as a late bubonic manifestation of the Second Plague Pandemic-offers a unique opportunity to reassess transmission dynamics in a prebacteriological context. Using a previously unexamined primary source consisting of daily counts of deaths, we combine historical analysis with a Bayesian epidemiological model to estimate the basic reproduction number ([Formula: see text]), the mean infectious period, and the case-fatality ratio in the towns of Son Servera and Capdepera (Mallorca, Spain). Our results show stark contrasts between the two towns: Son Servera exhibited a higher transmission potential ([Formula: see text]) and longer infectious period ([Formula: see text]2.8 d) than Capdepera ([Formula: see text]; [Formula: see text]2.0 d). The overall case-fatality rate of 78%-together with short infectious periods and historical descriptions of rapid clinical decline-strongly suggests that pneumonic and septicemic forms contributed substantially to transmission, challenging earlier interpretations centered on bubonic plague and rodent-borne spread. Historical evidence also rules out an enzootic rat reservoir, pointing instead to human ectoparasites or direct human-to-human routes as the most likely drivers. Moreover, mortality among children increased significantly during the outbreak, indicating age-differentiated vulnerability. By integrating quantitative modeling with fine-grained archival records, this study reassesses the biological nature of one of the last major plagues in 19th-century western Europe and contributes to broader debates on plague ecology, transmission mechanisms, and the dynamics of late Second Pandemic outbreaks.
2026-07-22 | Live attenuated vaccines alone or in combination with an adenovirus-based vaccine protect mice lacking IFN-γ against pneumonic plague.
Two live-attenuated vaccines, LMA and LMP, were evaluated alone or in combination with a trivalent adenoviral vector-based vaccine (Ad5-YFV) for their protective efficacy against pneumonic plague in wild-type (WT) and interferon-γ (IFN-γ) knockout (KO) mice. LMA and LMP comprise triple deletion mutants of Yersinia pestis CO92, which causes pneumonic plague, and Ad5-YFV incorporates three protective plague immunogens. Protection of 80 to 100% was observed in vaccinated mice when challenged with highly lethal intranasal doses of parental Y. pestis CO92. All vaccinated mice generated robust humoral and cellular immune responses. Immunized WT mice generated overall greater antibody responses in both serum and bronchoalveolar lavage fluid with higher percentages of polyfunctional T cell populations. Vaccinated IFN-γ KO mice displayed better B cell activity in germinal centers with higher percentages of activated antigen-specific and memory T cells. Superior lung immunity and recall immune responses were observed in both WT and IFN-γ KO mice immunized using a prime-pull vaccine strategy, which also provided full protection against pneumonic plague to mice lacking IFN-α, IFN-β, and IFN-γ receptors. Depletion of IFN-γ or tumor necrosis factor-α from immunized WT mice before and during infection did not reduce protection against pulmonary Y. pestis CO92 challenge. These data suggest that IFN-γ may not be required for protection against pneumonic plague by these vaccines. Combining live-attenuated and adenovirus-based vaccines resulted in augmentation of systemic and local immune responses, which could be beneficial in providing long-lasting immunity against pneumonic plague.
2026-07-08 | Protective outcomes of high-affinity monoclonal antibodies against drug-resistant plague strains.
Yersinia pestis, a category A infectious organism, is known to cause bubonic, septicemic, and pneumonic plague. With the emergence of streptomycin-resistant strains, there is an urgent need for new therapeutic strategies that can protect populations from Y. pestis infection. The main strategy for developing vaccines and therapeutic antibodies involves F1 antigen. Previous research has demonstrated that both human and murine monoclonal antibodies(mAbs) confer protective effects against Y. pestis infection. While, no relevant studies were identified on mAbs against drug-resistance Y. pestis. Here, we constructed an antibody library from Y. pestis vaccine strain EV76-immunized mice by phage display. The mAbs were baited by recombinant F1 antigen, and the biological functions of the obtained mAbs were assessed and evaluated in plague-challenged mice. For the Y. pestis strain 141 group, both Fm3 and Fm25 provided 100% protection at a dose of 100 µg. At 20 µg, only Fm3 conferred partial protection, with a survival rate of 25%, whereas all mice in the 4 µg treatment groups succumbed to infection within approximately 10 days. Against the drug-resistant Y. pestis strain S19960127, Fm25 at 100 µg resulted in complete survival, whereas Fm3 at the same dose conferred 75% protection. Neither mAbs showed protective efficacy at 20 µg or 4 µg, and all animals dying within approximately 10 days post-infection. These findings indicated that mAbs Fm3 and Fm25 confer protection against virulent and drug-resistant strains of Y. pestis.
2026-06-23 | Table 1_Protective outcomes of high-affinity monoclonal antibodies against drug-resistant plague strains.doc
Background Yersinia pestis, a category A infectious organism, is known to cause bubonic, septicemic, and pneumonic plague. With the emergence of streptomycin-resistant strains, there is an urgent need for new therapeutic strategies that can protect populations from Y. pestis infection. The main strategy for developing vaccines and therapeutic antibodies involves F1 antigen. Previous research has demonstrated that both human and murine monoclonal antibodies(mAbs) confer protective effects against Y. pestis infection. While, no relevant studies were identified on mAbs against drug-resistance Y. pestis. Methods Here, we constructed an antibody library from Y. pestis vaccine strain EV76-immunized mice by phage display. The mAbs were baited by recombinant F1 antigen, and the biological functions of the obtained mAbs were assessed and evaluated in plague-challenged mice. Results For the Y. pestis strain 141 group, both Fm3 and Fm25 provided 100% protection at a dose of 100 µg. At 20 µg, only Fm3 conferred partial protection, with a survival rate of 25%, whereas all mice in the 4 µg treatment groups succumbed to infection within approximately 10 days. Against the drug-resistant Y. pestis strain S19960127, Fm25 at 100 µg resulted in complete survival, whereas Fm3 at the same dose conferred 75% protection. Neither mAbs showed protective efficacy at 20 µg or 4 µg, and all animals dying within approximately 10 days post-infection. Conclusion These findings indicated that mAbs Fm3 and Fm25 confer protection against virulent and drug-resistant strains of Y. pestis.
2026-06-17 | Spatiotemporal dynamics of the capture rate of Rattus tanezumi and its implications for rodent-borne diseases in the Three Gorges Reservoir Area, China.
Rattus tanezumi (R. tanezumi) is a major amplifying host for plague and an important reservoir host for multiple zoonotic pathogens, including leptospirosis and hantavirus. Its population dynamics in the Three Gorges Reservoir (TGR) Area of China are influenced by climate and reservoir-induced environmental changes, thereby impacting disease transmission risks. Based on rodent capture rate data collected using cage traps during night surveys in January, March, May, July, September, and November each year from 2015 to 2021, this study investigated the spatiotemporal dynamics of R. tanezumi and its association with key meteorological and environmental factors. Using Geographic Information Systems (GIS) for spatiotemporal analysis and a Generalized Additive Model (GAM), we identified the current month's average temperature and relative humidity, together with 3-month-lagged precipitation and the Normalized Difference Vegetation Index (NDVI), as associated factors. The highest capture rate occurring at around 20 °C. Rat capture rate negatively correlated with both current relative humidity and lagged precipitation and a fluctuating decline with increasing lagged NDVI. This study demonstrates how climatic and environmental factors shape the spatiotemporal distribution of R. tanezumi population in the Three Gorges Reservoir Area. These findings provide insights that may inform predictions of rodent‑borne disease risks and support the development of targeted surveillance and control strategies in this ecologically vulnerable region.
2026-08-17 | The 1820 Mallorca plague was not a classic bubonic outbreak.
The 1820 plague outbreak in eastern Mallorca-long treated as a local episode and traditionally classified as a late bubonic manifestation of the Second Plague Pandemic-offers a unique opportunity to reassess transmission dynamics in a prebacteriological context. Using a previously unexamined primary source consisting of daily counts of deaths, we combine historical analysis with a Bayesian epidemiological model to estimate the basic reproduction number ([Formula: see text]), the mean infectious period, and the case-fatality ratio in the towns of Son Servera and Capdepera (Mallorca, Spain). Our results show stark contrasts between the two towns: Son Servera exhibited a higher transmission potential ([Formula: see text]) and longer infectious period ([Formula: see text]2.8 d) than Capdepera ([Formula: see text]; [Formula: see text]2.0 d). The overall case-fatality rate of 78%-together with short infectious periods and historical descriptions of rapid clinical decline-strongly suggests that pneumonic and septicemic forms contributed substantially to transmission, challenging earlier interpretations centered on bubonic plague and rodent-borne spread. Historical evidence also rules out an enzootic rat reservoir, pointing instead to human ectoparasites or direct human-to-human routes as the most likely drivers. Moreover, mortality among children increased significantly during the outbreak, indicating age-differentiated vulnerability. By integrating quantitative modeling with fine-grained archival records, this study reassesses the biological nature of one of the last major plagues in 19th-century western Europe and contributes to broader debates on plague ecology, transmission mechanisms, and the dynamics of late Second Pandemic outbreaks.
2026-07-22 | Live attenuated vaccines alone or in combination with an adenovirus-based vaccine protect mice lacking IFN-γ against pneumonic plague.
Two live-attenuated vaccines, LMA and LMP, were evaluated alone or in combination with a trivalent adenoviral vector-based vaccine (Ad5-YFV) for their protective efficacy against pneumonic plague in wild-type (WT) and interferon-γ (IFN-γ) knockout (KO) mice. LMA and LMP comprise triple deletion mutants of Yersinia pestis CO92, which causes pneumonic plague, and Ad5-YFV incorporates three protective plague immunogens. Protection of 80 to 100% was observed in vaccinated mice when challenged with highly lethal intranasal doses of parental Y. pestis CO92. All vaccinated mice generated robust humoral and cellular immune responses. Immunized WT mice generated overall greater antibody responses in both serum and bronchoalveolar lavage fluid with higher percentages of polyfunctional T cell populations. Vaccinated IFN-γ KO mice displayed better B cell activity in germinal centers with higher percentages of activated antigen-specific and memory T cells. Superior lung immunity and recall immune responses were observed in both WT and IFN-γ KO mice immunized using a prime-pull vaccine strategy, which also provided full protection against pneumonic plague to mice lacking IFN-α, IFN-β, and IFN-γ receptors. Depletion of IFN-γ or tumor necrosis factor-α from immunized WT mice before and during infection did not reduce protection against pulmonary Y. pestis CO92 challenge. These data suggest that IFN-γ may not be required for protection against pneumonic plague by these vaccines. Combining live-attenuated and adenovirus-based vaccines resulted in augmentation of systemic and local immune responses, which could be beneficial in providing long-lasting immunity against pneumonic plague.
2026-07-08 | Protective outcomes of high-affinity monoclonal antibodies against drug-resistant plague strains.
Yersinia pestis, a category A infectious organism, is known to cause bubonic, septicemic, and pneumonic plague. With the emergence of streptomycin-resistant strains, there is an urgent need for new therapeutic strategies that can protect populations from Y. pestis infection. The main strategy for developing vaccines and therapeutic antibodies involves F1 antigen. Previous research has demonstrated that both human and murine monoclonal antibodies(mAbs) confer protective effects against Y. pestis infection. While, no relevant studies were identified on mAbs against drug-resistance Y. pestis. Here, we constructed an antibody library from Y. pestis vaccine strain EV76-immunized mice by phage display. The mAbs were baited by recombinant F1 antigen, and the biological functions of the obtained mAbs were assessed and evaluated in plague-challenged mice. For the Y. pestis strain 141 group, both Fm3 and Fm25 provided 100% protection at a dose of 100 µg. At 20 µg, only Fm3 conferred partial protection, with a survival rate of 25%, whereas all mice in the 4 µg treatment groups succumbed to infection within approximately 10 days. Against the drug-resistant Y. pestis strain S19960127, Fm25 at 100 µg resulted in complete survival, whereas Fm3 at the same dose conferred 75% protection. Neither mAbs showed protective efficacy at 20 µg or 4 µg, and all animals dying within approximately 10 days post-infection. These findings indicated that mAbs Fm3 and Fm25 confer protection against virulent and drug-resistant strains of Y. pestis.
2026-06-23 | Table 1_Protective outcomes of high-affinity monoclonal antibodies against drug-resistant plague strains.doc
Background Yersinia pestis, a category A infectious organism, is known to cause bubonic, septicemic, and pneumonic plague. With the emergence of streptomycin-resistant strains, there is an urgent need for new therapeutic strategies that can protect populations from Y. pestis infection. The main strategy for developing vaccines and therapeutic antibodies involves F1 antigen. Previous research has demonstrated that both human and murine monoclonal antibodies(mAbs) confer protective effects against Y. pestis infection. While, no relevant studies were identified on mAbs against drug-resistance Y. pestis. Methods Here, we constructed an antibody library from Y. pestis vaccine strain EV76-immunized mice by phage display. The mAbs were baited by recombinant F1 antigen, and the biological functions of the obtained mAbs were assessed and evaluated in plague-challenged mice. Results For the Y. pestis strain 141 group, both Fm3 and Fm25 provided 100% protection at a dose of 100 µg. At 20 µg, only Fm3 conferred partial protection, with a survival rate of 25%, whereas all mice in the 4 µg treatment groups succumbed to infection within approximately 10 days. Against the drug-resistant Y. pestis strain S19960127, Fm25 at 100 µg resulted in complete survival, whereas Fm3 at the same dose conferred 75% protection. Neither mAbs showed protective efficacy at 20 µg or 4 µg, and all animals dying within approximately 10 days post-infection. Conclusion These findings indicated that mAbs Fm3 and Fm25 confer protection against virulent and drug-resistant strains of Y. pestis.
2026-06-17 | Spatiotemporal dynamics of the capture rate of Rattus tanezumi and its implications for rodent-borne diseases in the Three Gorges Reservoir Area, China.
Rattus tanezumi (R. tanezumi) is a major amplifying host for plague and an important reservoir host for multiple zoonotic pathogens, including leptospirosis and hantavirus. Its population dynamics in the Three Gorges Reservoir (TGR) Area of China are influenced by climate and reservoir-induced environmental changes, thereby impacting disease transmission risks. Based on rodent capture rate data collected using cage traps during night surveys in January, March, May, July, September, and November each year from 2015 to 2021, this study investigated the spatiotemporal dynamics of R. tanezumi and its association with key meteorological and environmental factors. Using Geographic Information Systems (GIS) for spatiotemporal analysis and a Generalized Additive Model (GAM), we identified the current month's average temperature and relative humidity, together with 3-month-lagged precipitation and the Normalized Difference Vegetation Index (NDVI), as associated factors. The highest capture rate occurring at around 20 °C. Rat capture rate negatively correlated with both current relative humidity and lagged precipitation and a fluctuating decline with increasing lagged NDVI. This study demonstrates how climatic and environmental factors shape the spatiotemporal distribution of R. tanezumi population in the Three Gorges Reservoir Area. These findings provide insights that may inform predictions of rodent‑borne disease risks and support the development of targeted surveillance and control strategies in this ecologically vulnerable region.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
3 orphan drug designations for Plague.
3 orphan drug designations for Plague.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
rF1V Vaccine with CpG 1018 | vaccines | FDA | 2026-08-17 | — | Dynavax Technologies Corporation |
Yersinia pestis plague recombinant antigen (rF1V; F1 capsular protein fused to V antigen; E. coli) vaccine with aluminum hydroxide | vaccines | FDA | 2016-11-30 | — | The Surgeon General, Department of the Army |
cethromycin | small molecules | FDA | 2009-09-09 | — | Advanced Life Sciences, Inc. |
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