Transcript
Ebola Hemorrhagic Fever
Jessica Davis
Madera Center
Microbiology 31
Professor Silva
March 23, 2011
Abstract
Although research on Ebola in usually restricted to level 4 bio-safety laboratories, researchers posit that the Ebola virus exists in nature and can therefore be retrieved from natural reservoirs and exploited as biological weapons. Ebola has the highest transmission and lethality rates. In addition, there is no effective vaccine or treatment against Ebola. These features make the Ebola virus, an ideal biological weapon. In addition, despite the increased public awareness and scientific breakthroughs, the recent Ebola epidemics in Uganda and Congo still resulted in the death of more than five hundred people. This highlights the possible debilitating impact which can occur, if the virus was used as a biological weapon. There is therefore need for researchers to increasingly focus on developing more effective means of diagnosing and controlling the transmissions of Ebola epidemics. This will lead to the effective prevention of Ebola epidemics in Africa.
Ebola Hemorrhagic Fever
There have been various outbreaks of Ebola hemorrhagic fever in Eastern and Central Africa. The cure has remained elusive and the key mandate has been aimed at understanding the pathogenesis of the disease. Of particular interest among researchers has been the need to understand the high virulence and accompanying lethality, with the aim of effecting appropriate control interventions during epidemic outbreaks. These efforts have been largely curtailed by the fact that research on the Ebola virus has remained restricted to specific level 4 laboratories due to its’ increased potential to be used for bioterrorism. While there is need to recognize the danger this virus poses, it is imperative to realize the fact that the Ebola virus is the most lethal virus and yet can be retrieved from natural reservoirs and used as a bio-weapon. There is therefore need for researchers to apply additional effort on developing better means of: diagnosing, preventing and controlling Ebola outbreaks.
Introduction: Definition and Characteristics
The Ebola virus causes hemorrhagic fever both in human beings and in non human primates (Towner et al., 2008). The Ebola virus is a member of the Filoviridae viruses. The Filoviridae family is characterized by enveloped, filamentous viruses with single stranded ribonucleic acid (Borio et al., 2002).
The occurrence of the Ebola epidemics has been restricted to the African continent. The first cases of Ebola were reported in 1976 in both Congo and Sudan. Subsequent infections have featured: Southern Sudan in 1979, Cote d' Ivoire and Gabon outbreaks in 1994, democratic republic of Congo in 1995, Uganda in 2001 and the latest 2009 epidemic in Congo (Hayman et al., 2010). This geographic preference could possibly be attributed to the climatic conditions.
To date, five different strains of the Ebola virus have been identified in Africa and America and have been named based on the location of incidence. These strains include: Reston, Zaire, Sudan, Ivory Coast, and more recently the Uganda strain; Bundibugyo ebolavirus (Towner et al., 2008). The species identified in Reston was posited to have initially been from Philippines (Towner et al., 2008).
The rate of mortality varies between the five species. Apart from the Cote d’ Ivoire stain which has no reported fatalities, the other viral strains have very high mortality rates (Borio et al., 2002). To this regard, the Zaire strain is the highest, exhibiting mortality rates of more than 90% in human beings (Borio et al., 2002). Researchers posit that the average mortality rates for the Ebola virus is approximately 71% (Borio et al., 2002). These rates are even higher among non human primates. The Zaire and Sudan strains are the most commonly occurring and have caused different outbreaks in Africa since their discovery in 1979. The Ivory Coast strain is however more rare with the last incident recorded, dating more than 17 years ago (Towner et al., 2008).
History
The use of hemorrhagic viruses as weapons of war was popularized by the Soviet Union and Northern America. This featured the mass production of Ebola and Marburg viruses for the sole mandate of use in war (Borio et al., 2002). In addition, apart from Ebola virus, the US government also experimented on Rift Valley fever viruses (Borio et al., 2002). After scientists successfully demonstrated the potential use of these hemorrhagic viruses as bio-weapons by successfully infecting primates, the Center for Disease Control and Prevention clustered these viruses as bio-weapons and implemented specific actions to ensure minimal transmission in cases of attack in 1999 (Borio et al., 2002). Key among these mandates was the development of a public awareness strategy. Despite improved awareness, the last attack in Gulu, Uganda still resulted in the death of more than four hundred individuals showing that there is need for more research on the control and prevention of Ebola (Towner et al., 2008).
Genetics
There is high genetic variation between the different strains. Studies examining the genetic variation between the different Ebola strains indicate at least 30% variation (Towner et al., 2008). This could most probably reflect mutational changes geared towards facilitating adaption to different geographic and climatic environments. These genetic changes could also infer evolutionary differences between different strains (Towner et al., 2008). The most recent strain was isolated from Uganda and is called Bundibugyo ebolavirus (Towner et al., 2008). It is closely related to the Ivory Coast strain. The fact that it shares genetic makeup with the core d’ Ivoire strain suggests another possible genetic link apart from geographical proximity since the two countries are in different parts of Africa (Towner et al., 2008).
Transmission
Ebola hemorrhagic fever has primarily been experienced in Africa. Different studies have posited the role of animal reservoirs in carrying and transmitting the Ebola virus. In this regard, researchers have asserted that the Zaire strain uses fruit bats as the main pathogen carrier (Hayman et al., 2010). Studies have also highlighted the role of arthropod carriers in transmitting the Ebola virus to mankind. This is largely thought to be possible through arthropod bites (Hayman et al., 2010). In addition, scholars have also observed that Ebola viruses may also be transmitted aerobically from dead animal carcasses to human beings (Borio et al., 2002).
Researchers have concluded that the bulk of infections occur after direct exposure to blood and various body secretions (Francesconi, et al., 2003). The mucosal membrane is thought to be particularly important in this mandate (Francesconi, et al., 2003). Infections acquired through direct contact are more likely to result to death. By using polymerase chain reaction, researchers have also detected the virus in the seminal fluid of patients, indicating the possibility of sexual transmission (Borio et al., 2002).
Human beings then spread the disease through contact with infected individuals. This mode of transmission has been particularly important in causing epidemiological outbreaks in African communities. Such outbreaks are unpredictable and often occur in remote areas without the necessary medical surveillance and infrastructure (Borio et al., 2002). This hinders public awareness and leads to more rapid rates of transmission. In addition, infection has been posited to also occur through airborne modes. However, the various epidemics which have been experienced in Africa have not been airborne and as a result have been controlled relatively easily (Borio et al., 2002). This has led to the conclusion that although airborne contamination is a possibility, it remains a minimal route of transmission.
Clinical Manifestations
Patients with Ebola hemorrhagic fever exhibit various symptoms during an Ebola outbreak. Key among these is a persistent high fever, characteristic of all hemorrhagic fevers. In addition, patients may also exhibit a characteristic rash. Initial symptoms during the incubation period also feature: migraines, lethargy, diarrhea and stomach pain (Borio et al., 2002). With advanced disease progression patients experience intravascular coagulation and accompanying severe bleeding, which are largely associated with shock (Borio et al., 2002). Research proves that most deaths are actually caused by the debilitating effects on endothelial cells as opposed to the severe bleeding (Borio et al., 2002).
Pathogenesis
Although there have been studies carried out in a bid to understand the immune mechanisms involved in an Ebola attack, these studies have been rare and collection of patient specimen is often impossible as a result of the geographic and infrastructural limitations in Africa where these epidemics occur. In spite of researchers’ inability to gain much access of human specimens, they have, by largely using non human primates, researchers have made a lot of progress in understanding the immune pathways accompanying the infection.
There are various differences in pathogenesis between the different viral strains. This distinction is largely based on the rate of disease progression. The disease pathway of the Zaire strain is the most unique. Researchers posit that this is as a result of the fact that this strain progresses very rapidly as evidenced by specific immune pathways (Geisbert et al., 2003).
The Ebola virus primarily targets the: renal, vasculature and respiratory systems. The virus initially attacks monocytes and macrophages. Researchers have observed that the virus then invades and uses: hepatic, endothelial and phagocytic cells to replicate in the body. The attack on the hepatic system leads to hepatic destruction while the compromised endothelial system leads to compromised effector cell activity and shock. In addition, the destruction of phagocytes, monocytes and macrophages inhibits inflammatory reactions and adaptive immune responses, triggering immunosuppresion (Geisbert et al., 2003). Immunosuppresion is also thought to result from the suppression of the major histocompatibility complex system which is integral in antigen processing and presentation (Geisbert et al., 2003).
Researchers have heralded the role of cell mediated immune responses in determining the successful outcome of therapy. To this regard, studies have indicated that although the humoral arm is imperative in preventing accompanying infections, cell mediated responses are integral in the actual recovery. The role of T cell responses including the production and signaling of various cytokines including: interleukin-2 and IFN-? has been studied (Geisbert et al., 2003). In addition, studies also associate the bleeding and intravascular coagulation to compromised platelet activity (Geisbert et al., 2003).
A critical interest in these studies has been attempting to understand the role of nitric oxide in the pathogenesis of the disease. The increased production of cytokines has been associated with an increase in nitrogen oxide levels (Geisbert et al., 2003). At normal levels, nitrogen oxide is an immune mediator. In addition, it is associated with regulating the cardiovascular system by inducing vasodilation. In cases of Ebola infection, the elevated nitric oxide levels are triggered by the overproduction of inflammatory cytokines. More specifically, this infection triggers an overproduction of nitrogen oxide synthase leading to an accompanying elevation in nitrogen oxide levels and causing cardiac malfunctions and the shock syndrome commonly associated with the fatality of Ebola infections (Geisbert et al., 2003).
Diagnosis
After collecting a patient history, the doctor uses PCR to confirm Ebola and rule out cases of malaria and typhoid. In the diagnosis of Ebola; blood samples are primarily analyzed for specific antigens and antibodies. However a key feature in the diagnosis is the fact that sample acquisition and testing must be conducted under extreme biologic containment since they pose a significant risk of transmission (Geisbert et al., 2003).
Management and Treatment
Patients infected by the Ebola virus require both treatment and palliative care. The treatment regimen is geared towards ensuring that they do not suffer from kidney and heart collapse as a result of the damage geared towards these biological systems (Borio et al., 2002). Key in this mandate is the need to ensure the availability of protective gear and equipment for barrier nursing and to curb airborne and contact transmission. In cases of expected exposure, researchers posit that exposed individuals should be isolated and medically monitored (Borio et al., 2002).
To prevent airborne transmission, scholars recommend the use of particulate respirators for any party who comes into contact with the patient (Borio et al., 2002). In addition, the patients should be contained in a locked room with a negative air pressure filter (Borio et al., 2002). Fulfilling this objective has been impossible in the African Ebola epidemics due to a limitation of resources. In such cases, patients are contained and particulate respirators are given to any other person who enters the room. In addition, in a bid to prevent infection, patient contact with uninfected parties is prohibited (Borio et al., 2002).
Supportive treatment features avid monitoring and regulation of fluid electrolyte balance. Doctors also monitor the patient for normal heart and fluid volumes. Hypotension is usually corrected by using intravenous infusions (Borio et al., 2002). However these infusions may trigger edema mandating the need for additional therapies (Borio et al., 2002). In cases of respiratory failure, patients receive mechanical ventilation aid (Borio et al., 2002).
Conclusion, the Ebola hemorrhagic fever poses a significant global biohazard risk. There is no cure and vaccine against Ebola. In addition, Ebola has the highest viral virulence and lethality rates. Researchers posit that although this virus is contained in level 4 laboratories, it can be retrieved from natural reservoirs and used as a bio-weapon. In the previous epidemics, although the virus was subsequently contained, it resulted to the death of many lives. It is therefore imperative for researchers to increasingly focus on developing more stringent means of preventing and addressing Ebola epidemics.
References
Borio, L., Inglesby, T., Peters, J., Schmaljohn, L., Hughes, J., Jahrling, B… (2002). Hemorrhagic fever viruses as biological weapons: Medical and public health management. Journal of American Medical Association 287, 2391 – 2405.
Francesconi,P., Yoti,Z., Declich, S., Onek, a., Fabiani, M., Olango, J… (2003). Ebola hemorrhagic fever: Transmission and risk factors of contacts, Uganda. Emerging Infectious Diseases 9, 1430-1437.
Geisbert T., Young, A., Jahrling, P., Davis, K., Larsen, T., Kagan, E… (2003). Pathogenesis of Ebola hemorrhagic fever in primate models: evidence that hemorrhage is not a direct effect of virus-induced cytolysis of endothelial cells. Am J Pathol.163, 2371-82.
Hayman, S., Emmerich, P., Yu, M., Wang, F., Suu-Ire, R., Fooks, A… (2010). Long-term survival of an urban fruit bat seropositive for Ebola and Lagos bat viruses. PLoS ONE 5. doi:10.1371/journal.pone.0011978
Towner, J., Sealy, T., Khristova, M., Albarino, G., Conlan, S., Reeder, S… (2008). Newly discovered Ebola virus associated with hemorrhagic fever outbreak in Uganda. PLoS Pathog 4. doi:10.1371/journal.ppat.1000212
