The Rare Responsibility: Unwelcome Guests

Dear Impossible Readers,

It was not too long ago when a single infectious disease disrupted daily life and overwhelmed healthcare systems worldwide. What was then unknown to many is now recognised globally as COVID-19. Beneath the vast body of medical knowledge lie the true gems of rare infectious diseases. These infections are often dramatic in their presentation and impact, yet they remain largely unfamiliar outside specialist circles. They are caused by unusual pathogens, ranging from amoebas and highly pathogenic viruses to prions. Their rarity makes them a constant puzzle for researchers and clinicians alike. Understanding these diseases is crucial for global health, as they challenge our diagnostic abilities and inspire innovative approaches to treatment and prevention.

Naegleriasis is caused by the free-living amoeba Naegleria fowleri, which enters the brain through the nasal passages after exposure to warm freshwater, leading to a rapidly fatal infection. In contrast, Marburg virus disease is a viral haemorrhagic fever with sporadic outbreaks in Africa, causing severe bleeding and organ failure. Nipah virus, another bat-borne virus, primarily triggers encephalitis and respiratory collapse with mortality exceeding seventy per cent, highlighting zoonotic spillover risks. Lassa fever, endemic to West Africa, is caused by a rodent-borne arenavirus. While most infections are mild, severe cases result in haemorrhagic fever and multi-organ damage. Lastly, Hendra virus, found in Australia, is transmitted from flying foxes to horses and occasionally to humans, causing acute respiratory and neurological disease. These five diseases illustrate the incredible diversity of rare infections. They differ by pathogen type, transmission route, geographical range, and clinical presentation, yet each can be deadly in its own way.

Treating these diseases remains a significant challenge. Naegleriasis has no widely effective therapy, though amphotericin B and a few experimental drugs have been used with limited success. Marburg and Nipah virus infections are primarily managed with supportive care, as approved antivirals are absent, but some experimental compounds show promise. Lassa fever responds to ribavirin if administered early, while supportive care remains crucial for severe cases. Hendra virus has seen partial success with monoclonal antibody therapy, yet the availability is limited, and most management focuses on intensive supportive treatment. Across all five diseases, early detection and supportive care are essential, emphasising the urgent need for more effective therapeutic strategies.

The future of treating rare infectious diseases depends on innovative technologies and new therapeutics. Rapid, point-of-care diagnostics using CRISPR-based detection or next-generation sequencing could enable identification within hours instead of days. For Naegleriasis, nanoparticle-delivered drugs or targeted brain-penetrating therapies may improve outcomes. Viral diseases like Marburg, Nipah, and Hendra are prime candidates for mRNA vaccines, monoclonal antibody cocktails, or broad-spectrum antivirals developed with AI-guided drug discovery. Lassa fever research is examining combination antivirals and immunomodulatory treatments that strengthen host response without causing harmful inflammation. Beyond therapeutics, advanced surveillance platforms combining environmental monitoring, AI-driven outbreak prediction, and real-time genomic analysis could prevent or control outbreaks before they spread.

These rare infectious diseases serve as a reminder that even a single case can have devastating effects, especially in areas where education and public health infrastructure are limited. While advanced research provides hope for improved treatments and quick diagnostics in the future, immediate action depends on awareness, prevention, and vigilance. Strengthening healthcare systems, raising awareness about diseases, and educating communities on high-risk exposures (e.g., avoiding contaminated water, limiting contact with potential animal carriers) are essential initial steps in safeguarding vulnerable populations. Understanding these rare infections is more than just an academic matter. Combining education, healthcare, and research infrastructure can significantly reduce the risks these rare diseases present.

The devastating potential of rare infectious diseases is most acute in regions with limited public health infrastructure, and is often compounded by complex socio-economic factors and systemic barriers that hinder effective prevention and response. While advanced research provides hope for future treatments, the most effective immediate strategy combines awareness with practical action. This requires a three-pronged approach: strengthening local healthcare, promoting widespread awareness, and educating communities on crucial prevention methods such as ensuring safe water and avoiding contact with animal carriers. Understanding these infections is therefore more than an academic matter. It requires a holistic approach that integrates research with robust public health to safeguard the most vulnerable populations.

Do not forget to pollinate,
Yours Possibly

Which rare disease category would you like to see covered next?

Further Reading

Coalition for Epidemic Preparedness Innovations (CEPI), (2025).[Accessed 23 September 2025].
Chen, L., Sun, M., Zhang, H., Zhang, X., Yao, Y., Li, M., Li, K., Fan, P., Zhang, H., Qin, Y. and Zhang, Z., 2024. Potent human neutralizing antibodies against Nipah virus derived from two ancestral antibody heavy chains. Nature Communications, 15(1), p.2987.
Mire, C.E., Chan, Y.P., Borisevich, V., Cross, R.W., Yan, L., Agans, K.N., Dang, H.V., Veesler, D., Fenton, K.A., Geisbert, T.W. and Broder, C.C., 2020. A cross-reactive humanized monoclonal antibody targeting fusion glycoprotein function protects ferrets against lethal Nipah virus and Hendra virus infection. The Journal of infectious diseases, 221(Supplement_4), pp.S471-S479.
Omar, R.F., Trottier, S., Sato, S., Ouellette, M. and Bergeron, M.G., 2025. Advances in the Management of Infectious Diseases. Infectious Disease Reports, 17(2), p.26.
Salam, A.P., Duvignaud, A., Jaspard, M., Malvy, D., Carroll, M., Tarning, J., Olliaro, P.L. and Horby, P.W., 2022. Ribavirin for treating Lassa fever: A systematic review of pre-clinical studies and implications for human dosing. PLoS Neglected Tropical Diseases, 16(3), p.e0010289.
Siddiqui, R., Lloyd, D., Alharbi, A.M. and Khan, N.A., 2024. Emerging therapies against Naegleria fowleri. Expert Opinion on Orphan Drugs, 12(1), pp.41-49.
Srivastava, S., Kumar, S., Ashique, S., Sridhar, S.B., Shareef, J. and Thomas, S., 2024. Novel antiviral approaches for Marburg: a promising therapeutics in the pipeline. Frontiers in microbiology, 15, p.1387628.
Wang, S., Li, W., Wang, Z., Yang, W., Li, E., Xia, X., Yan, F. and Chiu, S., 2024. Emerging and reemerging infectious diseases: global trends and new strategies for their prevention and control. Signal transduction and targeted therapy, 9(1), p.223.