Abstract

Entamoeba histolytica is a protozoan that causes amoebiasis and is a leading cause of morbidity and mortality in developing countries. Metronidazole is still the mainstay of treatment, but there is an emerging information in the literature that resistance can become a serious issue for management. In this article, we review the mechanisms of resistance, as well as the prevalence of drug-resistant E. histolytica; describe global recommendations; examine the economic burden that this emerging problem causes; and evaluate the current protocols in the different regions to determine whether new therapeutic options and vigilance strategies are necessary.

Introduction 

Amoebiasis is an infection caused by E. histolytica that mainly targets the gut, and it can sometimes result in serious issues, such as liver abscesses. Although metronidazole has been the go-to treatment for a long time, there are worries about its decreasing effectiveness, which points to a possible rise in resistance. This paper will look into what causes this drug resistance, how it affects healthcare systems, and how the world is responding to these challenges.

WHO Guidelines

The World Health Organization (WHO) advises:

Take Metronidazole (500–750 mg) three times daily for 7 to 10 days.

After that, consider a follow-up with a luminal agent like paromomycin.

Right now, there is no WHO warning about widespread resistance, but they stress the importance of monitoring and using medications wisely.

The rise of resistance shows the importance of refreshing WHO guidelines and keeping an eye on global drug safety.  

Methods

Literature Review: Analysis of studies (2010–2024) from PubMed, Scopus on resistance in E. histolytica.

In vitro Sensitivity Tests: Review of EC50 values for metronidazole, and new candidate GroupofDrugs.

Field Reports: Treatment failure cases  from endemic regions.

Policy Comparison: National treatments protocols from India, Mexico, Nigeria, and the USA.

Economic Impact

Health Costs: Increased hospitalization due to prolonged or ineffective treatments.

Workforce Loss: Reduced productivity of infected populations.

Drug Development Costs: Significant funding required for new anti-amoebic agents.

Global Inequities: Poorer nations face higher burdens due to lack of access to alternative treatments.

Country Protocols

1. India: Metronidazole as first-line, limited surveillance of drugs resistance.

2. Mexico: Similar to WHO protocols; some investments in diagnostic upgrades.

3. Nigeria: Dependence on clinical symptoms; underreporting and treatments failures common.

4. USA: Rare cases due to imported infections; reliance on CDC-recommended regimens.

Results

Multiple strains of E. histolytica show reduced sensitivity to metronidazole in vitro.

Treatment failure cases reported in India, Nepal, and Nigeria.

Countries lacking surveillance systems face higher treatment failure rates.

No fully resistants strains conclusively identified, but resistance is likely polygenic and slowly emerging.

Analysis

Resistance likely due to overuse, under-dosing, and poors compliance.

Limited alternative treatments options contribute to resistance selections pressure.

Genetic mechanisms include altered redox enzymes and drug uptake transporters.

Current WHO and national guidelines are not yet responsive to these emerging threats.

Discussion

Urgent need for updated WHO protocols addressing drug resistance.

Development of rapid diagnostic tests to differentiate resistant strains.

Investment in research for new anti-amoebic agents with novel mechanisms.

Regional collaborations can improve surveillance and share resistance data.

Conclusion

Emerging resistance in E. histolytica is a growing but under-recognized threat. Although full resistance is not widespread, warning signs demand urgent international attention. Updating treatment protocols, investing in diagnostics, and promoting stewardship of existing drugs are key steps forward.

References

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