Ebola Virus Disease - Coursework Example

EBOLA VIRUS DISEASE by + Introduction The largest ever-recorded Ebola Virus Disease (EVD) epidemic continues to ravage West Africa. The outbreak has forced international health community to react and medical professionals work indefatigably to aid suffering communities. The virus contains single-stranded RNA, and four of the five known species induce disease in humans. The present-day epidemic is caused by the Zaire strain which has previously been reported to have the mortality rate of 78%. As of today, the number of fatal cases has exceeded 9,500 (WHO 2015a). Causative Factor Ebola virus (EV) is a non-segmented single-stranded RNA virus which is similar to paramyxoviruses and rhabdoviruses in replication mechanisms and genome organization. It belongs to Filoviridae. The EV is enveloped, threadlike, and filamentous, has a nucleocapsid and extensive branching. Typically, the virus reaches 80 nm in diameter and 1000-1200 nm in length (Chippaux 2014). Formerly, EV and Marburg virus belonged to a group of haemorrhagic fever viruses, since they presented with impaired coagulation, bleeding, and shock. Nonetheless, the term haemorrhagic fever is no longer associated with EVD as the percentage of patients who actually develop acute bleeding is insignificant, and haemorrhage typically occurs in the terminal stage of illness. EV has five strains, namely Zaire, Sudan, Bundibugyo, Ivory Coast, and Reston. The next four produce a disease in humans: - First discovered in 1976, the Zaire virus has become the cause of numerous severe epidemics in Central African countries. Case-fatality rates range from 54 to 88 percent. Zaire strain is the causative factor of the outbreak in West Africa (WHO 1978; CDCP 1983). - The Sudan strain caused a number of outbreaks in Sudan and Uganda. Nearly half of the patients died in the 2000 Uganda epidemic. - The Bundibugyo species was found in 2007. It caused an outbreak in Uganda with a mortality rate of nearly 30 percent. This subtype resembles the Ivory Coast strain (WHO 2009). - The Ivory Coast virus has only been proven to induce illness in one individual, and that person survived. Presumably, the infection occurred when the zoologist operated on a dead chimpanzee found in the Tai Forest, where striking reductions in the ape population had been identified. The Reston virus, the last of the Ebola strains, is notably different from the four others since it seemingly circulates within an animal reservoir on the Philippine islands and has never been detected in Africa. This strain was brought to attention after an epidemic of fatal infection in macaques transported to the U.S. in 1989. Outbreaks among primates in the quarantine zones in the U. S. and Europe reoccurred until the Philippine animal importer terminated operations. No cases of disease were registered among the caretaking personnel. However, some of the members demonstrated signs of seroconversion. In 2008, an epidemic of severe illness affecting pigs occurred in the Philippines. The studies revealed both arterivirus and Reston virus in the infected animals. Serologic investigations identified IgG antibodies in some of the pig farmers. However, they never developed acute symptoms. Targets of the viral agents include macrophages, endothelial and dendritic cells, monocytes, and hepatocytes. The virus enters the cells by means of macropinocytosis. Once in the cytoplasm, the virus arrests the protein synthesis in the host cell and rapidly replicates. Inside the endothelial cell, a viral-coded glycoprotein complex attaches the virus to the internal surface of the intima. The virus also induces the secretion of the glycoprotein that reacts with signaling PMNs and therefore triggers the immune response. The PMNs delivers virions to the liver, lymph nodes, lungs, and spleen. Viral particles buddy and destroy host cells that send signals about the damage. Hence, fever and other symptoms of infection develop. Finally, the loss of vascular integrity results in hypovolemic shock (Bente & Strong 2009). Epidemiology The scientists discovered filovirus in 1967, when the incautious transportation of diseased monkeys from Uganda resulted in a massive epidemic of acute illness among the medical plant employees in the German city Marburg. The causative agent, dubbed the Marburg virus, has provoked a series of epidemics in Africa, the latest of which occurred in Uganda in 2014. Ebola virus, the second of the filoviridae genera, was first encountered in 1976 when two outbreaks exploded in Sudan and Zaire. Epidemics of EVD have been geographically limited to Sub-Saharan Africa. In 1995, an outbreak induced by the Zaire strain diseased several hundred people in Democratic Republic of the Congo, while over four hundred were exposed to the Sudan species five years later in the Ugandan region of Gulu (Bray & Daniel 2015). The current outbreak, caused by the Zaire virus, is the first to strike in West Africa and considerably exceeds all of the previous ones in magnitude and duration. 2014-2015 Outbreak The ongoing EVD outbreak began in Guinea, West Africa in December 2013. The epidemic is believed to have begun from a two-year-old child who was hospitalized with fever, black stool, and vomiting. The outbreak rapidly expended to Sierra Leone, Liberia, Nigeria, Mali, and Senegal. Sequence determination signified that the outbreak has resulted from maintained person-to-person transmission, with no contribution from animal reservoirs. The size of the outbreak, specifically in Sierra Leone and Liberia, has long been underestimated, for the most part, because many individuals infected with Ebola virus did not apply to the hospitals. As of 25 February 2015, the aggregate number of cases (suspected, probable, or confirmed) equals 23,825, including over 9650 deaths. The numbers include the minimum of 830 infected medical workers, nearly 60 percent of which have died (CDCP 2015a; WHO 2015b). In Nigeria, Mali, and Senegal, where transmission was localized, the outbreak is considered to have been eradicated. Cases of EVD have also been registered outside Africa. The first case in the U.S. was verified on September 30, 2014. The individual died on October 7. In December 2014, EV was extracted from a patient in the UK (Carroll, Brooks, & O’Carrell 2014). Transmission Outbreaks of EVD are believed to start when a person is exposed to the meat or bodily fluids of a diseased animal. Once an individual becomes sick, the virus is transmitted to those contacting with the patient’s skin, blood, saliva, and other body fluids. Laboratory studies on apes demonstrated that animals can get EV infection via droplet inoculation of virions into the eyes or mouth, implying that humans can become infected transferring viral agents on contaminated hands. Clinical Presentation Incubation period ranges between 3 and 8 days, thought, can last somewhat longer in repeated cases. In rare cases, incubation period may even reach 21 days. Sudden onset of clinical signs is typical of EVD. The early symptoms include fever, anorexia, myalgias, and acute headaches. Gastrointestinal syndrome (diarrhea, abdominal pain, nausea, and vomiting) develops soon. Signs of mucous membrane involvement involve dysphagia and conjunctivitis (CDCP 2015b). Bleeding from the GI tract has been observed in 40-50 percent of patients. A rash follows in in approximately 15 percent of cases. Terminally ill individuals are exhausted, blunt, tachypnoic, anuric, and often in shock. Ophthalmic complications were seen in 3 of 20 patients that survived in the 1995 Ebola outbreak in DRC. Photophobia, oculodynia, blurred vision, and excessive lacrimation were the common complaints. Some of the remote symptoms include hearing loss, orchitis, amenorrhea, and parotitis. Diagnosis Diagnosing Ebola on early stages is problematic as the symptoms in the first days are nonspecific. EV is only found in blood after many of the symptoms have developed. Some of the applicable laboratory tests are: Basic blood test Leukopenia, thrombocytopenia, lymphopenia occur early after virus reaches the blood stream. Neutrophilia follows soon and aminotransferases increase. Creatinine elevation appears with anuria. Tachypnea in fatally ill patients often results in metabolic acidosis. Virus isolation and molecular methods Isolation of the virus is performed using either tissue cultures or RT-PCR assay. Virus isolation in tissue culture is a dangerous procedure and can only be accomplished safely in a restricted number of leading laboratories in the world. RT-PCR was effectively applied for virus detection in the current epidemic as well as in some previous outbreaks. The EZ1 Real-time RT-PCR is among the most efficient methods of confirmation of the presence of the EV. The assay can be authorized only by the US Department of Defense, who choose laboratories that will cope with hazardous samples. The assay enables individuals suspected of infection to acquire the results of their tests few hours after the samples are taken. The method utilizes a dual-labeled FRET probe with a quencher and reporter dye (Biosearch Technologies 2014). High sensibility and speed of this assay have placed them in the forefront of diagnostics during several major disease outbreaks such as the 2009 H1N1 pandemic. Serological testing The indirect fluorescence antibody test (IFAT) rests on false-positive results. Worries over the specificity and sensitivity of this assay lead to the development of confirmatory tests. IgM and IG enzyme-linked immunosorbent assay (ELISA) tests may contribute to the diagnosis of EVD in individuals who have developed immune response. Both of the ELISA tests have proven sensitive and specific (Vogel 2014). During IgM-capture ELISA test, Zaire virus antigens incubated in Vero E6 cells are used to detect IgM antibodies to this species. In experimental apes, positive results are obtained within up to 6 days of infection. However, they are negative after longer periods. Such qualities suggest that the test should be used only in the early stages of the EVD (CDCP 2015c). IgG-capture ELISA with detergent-extracted viral antigens effectively detects IgG anti-EV antibodies. The specificity is higher than in the IFA, and the results remain positive for extended periods. Therefore, this test is seemingly the most effective among the known serological methods. Other studies The high risk and low accessibility of viral isolation boosted the invention of miscellaneous modalities that are more amenable in facilities with limited protection systems. Diagnostic tools used for confirmation of EV infection involve immunohistochemical test with the use of formaline-fixed peace of skin obtained from individuals who died from Ebola. The test is sensitive, specific, and safe. Large-scale application of electron microscopy in detection of viruses is not possible due to the low availability of the method in the exposed areas. Prevention The use of protective equipment is a primary measure for the caregiving personnel. Medical laboratorians are to follow the CDC guidelines based on three fundamental principles: 1. Healthcare workers delivering care for patients with Ebola must have undergone extensive training and have displayed competency in performing infections control procedures. 2. When working with PPE, there should be no skin exposed. 3. Compliance to safety measures in a facility with Ebola patients must be continuously monitored by a senior manager (CDCP 2015d). Vaccine against EV infection in primates has been developed in experimental studies on cynomoglus macaques. All of the vaccinated macaques contaminated with virus survived. However, the vaccine was proven ineffective in rhesus macaques. Trials with a possible vaccine against EV in humans are still ongoing. Treatment options Usually, treatment options in EVD patients are confined to supportive therapy and involve maintenance of intravascular volume, control of electrolytes, and proper nutrition. However, some newer therapies have been added recently. One of those is ZMAPP - a complex of three humanized monoclonal antibodies. After a series of positive experiences in primates the remedy was tried on humans (Qiu & Wong 2014). The numbers are yet insufficient to estimate its efficacy. Outlook The Ebola outbreak prognoses have improved significantly in 2015 as medical professionals observe the weakening of the epidemic in West Africa. The WHO reports that the incidence continues to decrease in Liberia, Guinea, and Sierra Leona. In addition, the outbreak is considered to have been eliminated in nearby Mali (Dallas 2015). Conclusion EVD has caused one of the most severe epidemics in the recent history, becoming the reason of over 9,500 deaths and leaving almost 16,000 children without family care (UNICEF 2015). The case has mobilized the world health community. The most innovative diagnostic methods are being harnessed and vaccine is under way. Statistics in the beginning of 2015 give arguments for a positive outlook for the future. 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