Drug-resistant Mpox strains discovered in five American states

Medical News: In a concerning development, U.S. health officials have identified a cluster of drug-resistant mpox cases across five states. The cases, caused by an mpox variant resistant to the antiviral tecovirimat (TPOXX), mark a significant public health challenge. This Medical News report discusses the details of the cluster, the implications for public health, and what this means for future treatments.


Drug-resistant Mpox strains discovered in five American states

Overview of the Discovery
Between October 6, 2023, and February 15, 2024, 18 individuals from California, Illinois, Louisiana, New York, and Texas were diagnosed with a strain of mpox that had developed resistance to tecovirimat. These patients had never taken the drug before, raising concerns that the virus could be evolving resistance naturally. The study that reported these cases, which was published in the U.S. Centers for Disease Control and Prevention’s (CDC) Morbidity and Mortality Weekly Report, sheds light on the spread of this resistant strain and its potential to affect public health across state borders.
 
The identification of this resistant mpox strain comes after an earlier unrelated cluster of drug-resistant cases in California in late 2022 and early 2023. The new cluster, however, involves multiple states, making it a more widespread issue. Health officials are concerned that these cases could be underreported, as not all mpox infections are sequenced to identify the virus variant responsible for the infection. Therefore, the true number of resistant cases could be higher than currently known.
 
The Role of Tecovirimat and Drug Resistance
Tecovirimat, marketed as TPOXX by Siga Technologies, is one of the few antiviral treatments available for mpox. It works by targeting a protein in the virus called F13, which is essential for the virus to replicate and spread. However, mutations in the F13 protein can render the drug ineffective, which has been seen in previous cases involving prolonged treatment of severely immunocompromised patients. The resistance in this latest cluster is thought to have developed naturally without prior drug exposure, which is particularly concerning for public health efforts.
 
CDC officials emphasized that this resistance highlights the need for regular surveillance to monitor drug effectiveness. Without proper monitoring, more resistant strains could emerge and spread. They also called on healthcare providers to ensure that patients follow the proper protocol when taking tecovirimat, including adherence to dosage and the timing of medication to prevent the spread of the virus while on treatment.
 
Genetic Findings of the Resistant Strain
The study found that the drug-resistant mpox cases were caused by a unique combination of mutations in the F13 gene, specifically an asparagine deletion at position 267 (N267del) and an alanine-to-threonine substitution at position 184 (A184T). These mutations were present in 20 samples from 18 patients, spread across the five states. Genetic sequencing revealed that this new c luster was distinct from the earlier cluster seen in California, indicating that the mutations likely originated from a common ancestor before spreading between states.
 
Notably, none of the 16 patients with available treatment histories had taken tecovirimat before, confirming that the resistance had developed independently of previous drug exposure. In laboratory tests, the samples showed resistance to the drug, with a 177- to 583-fold increase in the concentration required to inhibit the virus, compared to a reference strain. This degree of resistance suggests that tecovirimat would not have been effective in treating these patients.
 
Public Health Implications
The discovery of drug-resistant mpox strains in multiple states raises concerns about the future of mpox treatment and prevention. Given that the virus can spread through close physical contact, including sexual contact, the potential for resistant strains to spread is significant. This is especially true because not all mpox cases undergo genetic sequencing, meaning the actual prevalence of resistant strains could be higher than reported.
 
Health officials are now calling for increased surveillance to monitor for resistant strains and to track the spread of the virus. This includes routine genetic sequencing of mpox cases to identify resistance patterns early. Without such monitoring, there is a risk that resistant strains could spread unchecked, leading to more cases that are difficult to treat.
 
Additionally, the CDC stressed the importance of following proper protocols when prescribing tecovirimat. This includes ensuring that patients take the correct dosage, adhere to the recommended schedule, and follow dietary instructions, such as taking the medication with a fatty meal to improve absorption. Proper usage of the drug is essential in preventing the spread of resistant strains.
 
Urgent Need for New Treatments
The findings of this study underscore the urgent need for new treatments for mpox. Tecovirimat is one of the few approved treatments for mpox, and if resistance continues to spread, it could become ineffective. Researchers are now calling for the development of additional antiviral drugs to treat mpox and other orthopoxvirus infections, such as smallpox, which remains a bioterrorism threat.

The resistance seen in these mpox cases also highlights the limitations of relying on a single drug for treatment. As viruses evolve, they can develop resistance to treatments, rendering them less effective or completely ineffective. This is why it is crucial to have multiple treatment options available, particularly for diseases like mpox that can cause severe illness in immunocompromised individuals.
 
Conclusion
The identification of drug-resistant mpox strains in five U.S. states is a wake-up call for public health officials and researchers alike. The fact that these strains developed resistance without prior exposure to tecovirimat is alarming and suggests that the virus may be evolving in ways that could undermine current treatment efforts.
 
Surveillance and adherence to treatment protocols are critical in preventing the spread of these resistant strains. Moreover, the urgent need for new antiviral treatments cannot be overstated. Without additional treatment options, the healthcare system may struggle to manage future outbreaks of drug-resistant mpox.
 
The study findings were published in the peer-reviewed journal Morbidity and Mortality Weekly Report.
https://www.cdc.gov/mmwr/volumes/73/wr/mm7340a3.htm
 
For the latest Mpox News, keep on logging to Thailand Medical News.
 
Read Also:
https://www.thailandmedical.news/news/siga-technologies-faces-major-legal-issues-as-its-mpox-drug-tpoxx-tecovirimat-fails-and-its-cmo-is-terminated
 
https://www.thailandmedical.news/news/u-s-niaid-and-harvard-study-reveals-antibodies-from-jynneos-mpox-vaccine-wane-after-6-to-12-months