Posted: March 24th, 2023
Summary of the Article
Over the years, Central Africa has experienced sporadic outbreaks of Ebola virus (EBOV) infections. The most recent and largest outbreak was experienced between 2013 to 2016. The outbreak that occurred in West Africa led to over 27,000 infections and more than 11,000 fatalities. The seriousness of this care has resulted in calls for effective interventions to address Ebola virus disease (EVD). The article “The Toll-Like Receptor 4 Antagonist Eritoran Protects Mice from Lethal Filovirus Challenge” by Younan, Ramanathan, Graber, Gusovsky, and Bukreyeva (2017) is based on the incident and the growing need to create effective medical interventions to counter such severe infections. Previous evidence has revealed some common characteristics between the Ebola virus and the beginning of bacterial sepsis, such as the onset of a “cytokine storm.” Therefore, researchers investigated the impact of Eritoran, a Toll-like receptor 4 (TLR4) antagonist as an intervention.
Previous studies have revealed the effectiveness of Eritoran as an intervention in protecting mice against lethal influenza virus. In mice, the study reports that eritoran is an effective protection against the lethality of Ebola virus and the related Marburg virus (MARV). The study revealed that a daily dose of the drug reduced clinical symptoms of the disease and achieved a reduction in viral titers. Blood analysis after treatment revealed that the drug reduced granulocytosis regardless of the evident rise in the proportion of activated neutrophils. However, the study did not reveal an increase in CD3_ T lymphocytes regardless of the improved rate of survival and decreased viremia. Consequently, lymphopenia was found to be more in the mice treated using eritoran. However, the general decrease in the cytokines, chemokines, and free radical levels was evident in the study (Younan, Ramanathan, Graber, Gusovsky, & Bukreyeva, 2017). Thus, it was posited that the treatment was potentially effective in alleviating the “cytokine storm’s” severity.
The conclusion made by Younan, Ramanathan, Graber, Gusovsky, and Bukreyeva (2017) relate to the possibility of viremia to provide effective intervention in the “cytokine storm.” Furthermore, they suggested the possibility of the drug offering effective treatment to change the cytokine responses’ kinetics. Therefore, the study is among the categories that have proven the impact of TLR4 in the Ebola virus pathogenesis. The results revealed the need for further research on the efficacy of the intervention in the treatment of EBOV and MARV infections in humans. Conclusive results on the efficacy of the intervention will help to alleviate the seriousness of the infections in the most affected parts of the world such as Central Africa.
Regardless of the inspiring results from the study, some limitations and gaps were evident. The studies used lab mice just as in other studies on drugs and other medical interventions. While mice are believed to have clinical similarities with humans, such studies cannot have conclusive evidence of the efficacy of the treatment in humans. However, they reveal that researchers are in the right direction to develop medical interventions. The target infections, influenza virus, and Ebola virus, differed in terms of their effect on mice. Unlike the lethal influenza virus, which did not result in lethal infection in TLR4_/_ mice, the Ebola virus proved to be lethal in TLR4_/_ mice and the wild-type (wt). Although the infections cause a serious cytokine storm, filoviruses bring systemic infections while influenza virus results in localized infections of respiratory epithelium (Younan, Ramanathan, Graber, Gusovsky, & Bukreyeva, 2017). Therefore, it was difficult to have conclusive results on the effectiveness of the treatment. Hence, additional research on the effect of eritoran in the treatment of the two types of viruses is required.
Area of Interest
Filovirus infection is the selected area of interest. The virus belongs to the Filoviridae family and results in severe hemorrhagic fever in the affected human beings as well as in non-human primates (Faye et al., 2015). The virus is known to cause multiple hemorrhagic manifestations, characterised by disseminated intravascular coagulation, marked hepatic involvement, and shock. The virus is a major cause of death in humans because fatality occurs between six and sixteen days after the manifestation of the virus. Various genera of the Filovirus infections have been identified. Ebola virus (species Zaire ebolavirus) is one of the most common genera in the family. The infections are associated with high mortality rates of between 30% and 90%, according to the viral infection (Rewar & Mirdha, 2014). The high rate of morality motivates comprehensive research on effective interventions.
The main reason for the choice of the area of interest is the fatality caused by filovirus infections and the speed with which the infections manifest and proceed to affect humans. Clinical signs of the infections such as Ebola develop early. However, they cause death within a few days after manifestation. Furthermore, the high rate of mortality from the infections is another reason for the interest in this area. The infections cause serious effects on the bodies and organs of infected individuals. Biochemical and clinical results reveal extensive involvement of the liver, alterations in vascular permeability, renal damage, and the clotting cascade activation (Mekibib & Ariën, 2016). The severe impact of the disease causes interest in the subject, including the need for clinicians and other medical researchers and practitioner to develop effective treatment and interventions to control epidemics caused by filovirus infections.
The topic of Filovirus infections is important for the public because of the severe impact on individuals and society. The viruses are highly infectious, indicating that they spread very fast after the initial contact. Once a single person is infected, the virus can move from one person or non-human primate to another within a very short period. Therefore, the public should understand the clinical manifestations of the virus to seek immediate medical assistance if a symptom is recorded. Another reason for the heightened public interest is the speed with which the infections cause death. Following the initial contact with the virus, death can occur within within six and sixteen days. Therefore, people should learn the importance of seeking timely intervention to prevent fatality and lower the rate of mortality caused by such infections.
Critical Review of Area of Interest
Although various aspects of Filovirus infections are known, others remain unknown such as the transmission of the virus from a natural reservoir to humans. However, research shows that after the initial infection in a human subject, others may acquire the virus through person-to-person contact (Osterholm et al. 2015). According to Mekibib and Ariën (2016), the virus is highly contagious, and its transmission involves close contact between the person who is infected or their body fluids. For example, during the outbreaks of the infections such as Ebola, people who cared for or operated in close contact with the infected persons were at a high risk of infection. Nosocomial (hospital) transmission has been evident through the reuse of unsterilised devices, such as needles, syringes, and contact with infected fluids (Anthony & Bradfute, 2015). Therefore, researchers caution about the importance of exercising care when handling an infected person or equipment.
Researchers reveal the need to understand the clinical manifestations of Filoviral hemorrhagic fever to ensure timely intervention. Some of the common signs include severe hemorrhage through various body openings, disseminated intravascular coagulation, hepatic involvement, and shock (Anthony & Bradfute, 2015). Medical experts advise people to seek immediate medical attention in case of any of the manifestations to increase the chances of survival. However, Hoenen and Feldmann (2014) note that there is no effective vaccine for viruses. Therefore, it is important for the person to receive a timely diagnosis to benefit from immediate intervention. Furthermore, they recommend isolation to prevent further infections. Quarantine is used even after the identification of a single case of the virus to curtail an epidemic. Since no virus-specific treatment exists, practitioners use supportive therapy (Messaoudi, Amarasinghe, & Basler, 2015). Regardless of the limitation in the treatment of the infections, timely intervention is critical.
Epidemics are health burden to individuals and society, especially those involving highly infectious diseases such as Filovirus infections. Unfortunately, the infections tend to spread far and wide because of the increased contact between people, or between people and animals, increased mobility through revolutionized transport systems, changes such as global warming, and increased economic production such as land cultivation. The high risk necessitates the development of effective interventions to counter a possible epidemic. The One Health framework is relevant in the effort because of recommendations to design and implement intervention programs, policies, and legislation to coordinate efforts to address such health challenges.
Regardless of the historical manifestations of Filovirus infections in various parts of the world, including Central Africa, research remains inconclusive about an effective treatment or medical intervention for such infections. Therefore, collaborative efforts remain critical to research, as well as designing and implementing effective interventions. Notably, the use of Eritoran has been found effective in treating some of the viruses in mice, including Ebola and Influenza, pointing out to a future success. Therefore, more research is critical to investigate the treatment and other control measures that would prevent high rates of mortality from the infections.
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