RARE DISEASE
Yellow fever
Yellow fever
Yellow fever
Synonyms: Bronze John, YF, Yellow Jack
Synonyms: Bronze John, YF, Yellow Jack
Synonyms: Bronze John, YF, Yellow Jack
Drug discovery
0
drugs
With orphan designations
Overview
Yellow fever is a mosquito-borne flavivirus infection endemic in tropical regions of Africa and South America. It presents with symptoms ranging from mild febrile illness to severe manifestations like jaundice, hemorrhage, and multi-organ failure, with a case fatality rate of 30–60% in severe cases [1][4][12]. Diagnosis relies on RT-PCR, viral culture, or serologic testing [1][13]. Prevention centers on vaccination (single dose provides lifelong immunity) and mosquito control [13][15][18]. No antiviral treatment exists; management is supportive, focusing on symptom relief and complications [1][9][17].
Population
Primarily affects 34 countries in sub-Saharan Africa and 13 countries in Central/South America [1][14][18].
Highest burden in the Democratic Republic of Congo and Brazilian Amazon due to high transmission intensity and low vaccination coverage [2][3][15].
At-risk groups include unvaccinated travelers, rural workers, and children in endemic regions (accounting for 71% of cases under age 30) [6][16].
Burden
Annual estimates: 109,000 severe cases (67,000–173,000) and 51,000 deaths (31,000–82,000) globally [2][3][11].
Africa accounts for 92% of global burden, with case fatality rates up to 12% in recent outbreaks [6][11][15].
Underreporting persists due to nonspecific symptoms and limited diagnostics; true cases may be 10–250× higher than reported [7][13].
Therapies
Supportive care: Fluid management, bleeding prophylaxis (vitamin K, H₂ blockers), and monitoring for organ failure [1][17].
Vaccination: 17D vaccine prevents >99% of cases within 30 days; mass campaigns averted 47% of deaths in Africa [3][13][15].
Outbreak response: Emergency vaccination, enhanced surveillance, and insecticide-treated bed nets [6][13][16].
Categories: rare infectious diseases
Research Papers
1,242 drug discovery papers about Yellow fever, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,242 drug discovery papers about Yellow fever, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-11 | Formulation and stability design spaces for a new yellow fever vaccine.
Yellow fever (YF) is a life-threatening disease that is entirely preventable through vaccination. The objective of this study was to formulate a freeze-dried presentation of a live-attenuated, Vero cell-based yellow fever vaccine (vYF) with improved manufacturability and enhanced shelf-life. Considering four critical quality attributes (i.e., glass transition temperatures and infectious titers at two time points), a comprehensive formulation screening was performed to identify an optimal combination of excipients, capable of protecting the virus during lyophilization while ensuring long-term stability of the vYF infectious titer. Overall, L-proline, urea, and poloxamer 407 demonstrated a stabilizing effect, and the application of an advanced kinetic model enabled prediction of a 60-month shelf-life at 5 °C for the formulated vaccine. Machine learning models were used to build both formulation and stability design spaces that defined global stabilizing regions within the explored concentration ranges of each excipient. This study demonstrates that the combination of systematic excipient screening and advanced analytics enables the selection of robust formulations with long-term stability within an accelerated development timeframe. The developed vaccine formulation has the potential for large-scale industrial production and can address substantial market demand in the coming years, representing a significant advancement in vYF technology.
2026-07-11 | Coagulopathy in viral haemorrhagic fevers and beyond: molecular mechanisms and targeted interventions.
Coagulopathy refers to any medical condition which affects the ability of the blood to clot. It can be caused due to genetic conditions like haemophilia, von Willebrand disease, or it can be caused through liver disease or deficiency of Vitamin K. It also involves a broad range of diseases affecting hemostasis as an unbalanced and even bidirectional relationship between thrombosis and bleeding. Coagulopathy can also be caused by thromboinflammation, as seen in VHFs like Ebola, Dengue, Marburg, Crimean-Congo Hemorrhagic Fever, Yellow Fever, and Hantavirus infection. The immune response and coagulation system are intricately linked in such cases. Infections from VHFs cause endothelial cell dysfunction through the immune response, monocytes/macrophages activation, and increased expression of tissue factor (TF), which in turn causes excessive thrombin production and fibrin formation. These conditions result in microvascular thrombosis, organ dysfunction, consumption of platelets and coagulation factors, causing a balanced but fragile state of hemostasis that could tip over towards either thrombosis or bleeding. New therapies have been developed that interfere with these processes, such as interference with the TF pathway (for instance, rNAPc2) and regulation of fibrinolysis (tranexamic acid). The recognition of the double-edged sword of coagulopathy is critical for the development of treatment strategies targeting coagulation disorders. This literature review discusses the molecular basis of immunothrombosis and endothelial dysfunction in VHFs.
2026-07-11 | Ecological and engineered modulation of the mosquito microbiome: mechanisms, vector competence, and translational prospects for disease control.
Malaria, dengue fever, Zika, chikungunya, yellow fever, and West Nile fever are mosquito-borne diseases that collectively impose an enormous global health burden, disproportionately affecting low- and middle-income countries where vector-control tools remain limited or compromised by insecticide resistance. Over the past two decades, the characterization of mosquito-associated microbiomes has transformed our understanding of vector biology, revealing complex, ecologically contingent assemblages of bacteria, fungi, viruses, and protists that profoundly influence mosquito physiology, immunity, and pathogen transmission competence. This review synthesizes current knowledge on the composition and determinants of the mosquito microbiome across major vector genera-Aedes, Anopheles, and Culex-and critically evaluates evidence for microbiome roles in larval development, adult fitness, immune homeostasis, and pathogen-vector interactions. We examine how resident microbiota can inhibit or, in some contexts, facilitate pathogen establishment, dissemination, and transmission, and we discuss the mechanistic pathways underlying these effects, including immune priming, niche competition, antimicrobial metabolite production, and modulation of midgut barrier integrity. We then review major strategies for deliberate microbiome modulation, including Wolbachia-based pathogen blocking and population suppression, paratransgenesis, symbiont supplementation, microbiota engineering, and habitat-level manipulation, and evaluate their biological rationale, current evidence base, field feasibility, and limitations. Attention is given to the gap between laboratory proof-of-concept and operational deployment, as well as to biosafety, regulatory, ecological, and ethical challenges that must be resolved before microbiome-based interventions can be integrated into public health programs. We conclude by identifying priority research questions and the technological advances most likely to accelerate progress from descriptive microbiome science to predictive, actionable vector control.
2026-07-11 | Formulation and stability design spaces for a new yellow fever vaccine.
Yellow fever (YF) is a life-threatening disease that is entirely preventable through vaccination. The objective of this study was to formulate a freeze-dried presentation of a live-attenuated, Vero cell-based yellow fever vaccine (vYF) with improved manufacturability and enhanced shelf-life. Considering four critical quality attributes (i.e., glass transition temperatures and infectious titers at two time points), a comprehensive formulation screening was performed to identify an optimal combination of excipients, capable of protecting the virus during lyophilization while ensuring long-term stability of the vYF infectious titer. Overall, L-proline, urea, and poloxamer 407 demonstrated a stabilizing effect, and the application of an advanced kinetic model enabled prediction of a 60-month shelf-life at 5 °C for the formulated vaccine. Machine learning models were used to build both formulation and stability design spaces that defined global stabilizing regions within the explored concentration ranges of each excipient. This study demonstrates that the combination of systematic excipient screening and advanced analytics enables the selection of robust formulations with long-term stability within an accelerated development timeframe. The developed vaccine formulation has the potential for large-scale industrial production and can address substantial market demand in the coming years, representing a significant advancement in vYF technology.
2026-07-11 | Coagulopathy in viral haemorrhagic fevers and beyond: molecular mechanisms and targeted interventions.
Coagulopathy refers to any medical condition which affects the ability of the blood to clot. It can be caused due to genetic conditions like haemophilia, von Willebrand disease, or it can be caused through liver disease or deficiency of Vitamin K. It also involves a broad range of diseases affecting hemostasis as an unbalanced and even bidirectional relationship between thrombosis and bleeding. Coagulopathy can also be caused by thromboinflammation, as seen in VHFs like Ebola, Dengue, Marburg, Crimean-Congo Hemorrhagic Fever, Yellow Fever, and Hantavirus infection. The immune response and coagulation system are intricately linked in such cases. Infections from VHFs cause endothelial cell dysfunction through the immune response, monocytes/macrophages activation, and increased expression of tissue factor (TF), which in turn causes excessive thrombin production and fibrin formation. These conditions result in microvascular thrombosis, organ dysfunction, consumption of platelets and coagulation factors, causing a balanced but fragile state of hemostasis that could tip over towards either thrombosis or bleeding. New therapies have been developed that interfere with these processes, such as interference with the TF pathway (for instance, rNAPc2) and regulation of fibrinolysis (tranexamic acid). The recognition of the double-edged sword of coagulopathy is critical for the development of treatment strategies targeting coagulation disorders. This literature review discusses the molecular basis of immunothrombosis and endothelial dysfunction in VHFs.
2026-07-11 | Ecological and engineered modulation of the mosquito microbiome: mechanisms, vector competence, and translational prospects for disease control.
Malaria, dengue fever, Zika, chikungunya, yellow fever, and West Nile fever are mosquito-borne diseases that collectively impose an enormous global health burden, disproportionately affecting low- and middle-income countries where vector-control tools remain limited or compromised by insecticide resistance. Over the past two decades, the characterization of mosquito-associated microbiomes has transformed our understanding of vector biology, revealing complex, ecologically contingent assemblages of bacteria, fungi, viruses, and protists that profoundly influence mosquito physiology, immunity, and pathogen transmission competence. This review synthesizes current knowledge on the composition and determinants of the mosquito microbiome across major vector genera-Aedes, Anopheles, and Culex-and critically evaluates evidence for microbiome roles in larval development, adult fitness, immune homeostasis, and pathogen-vector interactions. We examine how resident microbiota can inhibit or, in some contexts, facilitate pathogen establishment, dissemination, and transmission, and we discuss the mechanistic pathways underlying these effects, including immune priming, niche competition, antimicrobial metabolite production, and modulation of midgut barrier integrity. We then review major strategies for deliberate microbiome modulation, including Wolbachia-based pathogen blocking and population suppression, paratransgenesis, symbiont supplementation, microbiota engineering, and habitat-level manipulation, and evaluate their biological rationale, current evidence base, field feasibility, and limitations. Attention is given to the gap between laboratory proof-of-concept and operational deployment, as well as to biosafety, regulatory, ecological, and ethical challenges that must be resolved before microbiome-based interventions can be integrated into public health programs. We conclude by identifying priority research questions and the technological advances most likely to accelerate progress from descriptive microbiome science to predictive, actionable vector control.
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