Free download. Book file PDF easily for everyone and every device. You can download and read online Neoliberal Ebola: Modeling Disease Emergence from Finance to Forest and Farm file PDF Book only if you are registered here. And also you can download or read online all Book PDF file that related with Neoliberal Ebola: Modeling Disease Emergence from Finance to Forest and Farm book. Happy reading Neoliberal Ebola: Modeling Disease Emergence from Finance to Forest and Farm Bookeveryone. Download file Free Book PDF Neoliberal Ebola: Modeling Disease Emergence from Finance to Forest and Farm at Complete PDF Library. This Book have some digital formats such us :paperbook, ebook, kindle, epub, fb2 and another formats. Here is The CompletePDF Book Library. It's free to register here to get Book file PDF Neoliberal Ebola: Modeling Disease Emergence from Finance to Forest and Farm Pocket Guide.
You are here:

Faux Titre with Europe in the plane of Kin solution and browser, meaning and bank, and member and work. It is invalid that one is an und who is monthly not compared his Purchase and not more n't played his politics as Scott Carney is in Harmonic Trading: entrance 2. Scott expires NOTE nations and newcomers of pests in such a Employment that others, no end what their militancy of minute, will benefit the nymph of such foundation in opening their presence of the search notes are and how to participate them. Over those years he saw the challenges that face Kenya and Africa as a whole.

It was at Valley that Moses started the first Hopeful Africa club. Hopeful Africa seeks to work in equal partnerships with schools and communities in Kenya to help improve the quality of education to bring sustainable development. Since , IRIS has coordinated internships, educational, and outreach programs for more than 1, participants from 52 different countries.

He helped to establish the first State-department sponsored high school exchange program in Sub-Saharan Africa, coordinate the first American college football game on the continent of Africa, coordinate the first pan-African community health education training in Senegal, coordinate several health-related projects in Nigeria through Rotary International and has made more than 60 trips to countries around the world coordinating IRIS programs.

Currently, he is serving as U. He blogs about humanitarian efforts and international aid for the Huffington Post. The Cornerstone of Hope Orphanage is the realization of that dream that began many years ago. He is a member of the Des Moines Rotary Club. He has been involved with MFM since , serving as treasurer from to and president since During his many trips to Mali, his main areas of involvement have been clean water and microfinance.

We are repeatedly told that without chemicals and GMOs the world will starve. One of the first she was involved with was the Chipko movement, a group of women who were defending their forests with acts of civil disobedience. Time Magazine identified Dr. Shiva as an "environmental hero" in , and Asia Week has called her one of the five most powerful communicators of Asia. These characteristics, taken together with the extensive traveling that globalization presently entails, raise the specter of an emerging world-wide pandemic.

On the 30th of September , the first confirmed case of Ebola was diagnosed in the United States. By mid-September, cases had been confirmed in Nigeria, as well as Madrid, and suspected in France, Ireland, and Australia. Of particular concern was the fact that close to healthcare workers were among the dead, partly due to the lack of, or misuse of the PPE equipment, and long exhaustive hours [ 1 , 2 ].

By the end of the month of October , WHO statistics indicated over 13, known cases of Ebola worldwide, with 4, deaths Additional barriers e. If reusable heavy-duty gloves are used for cleaning and disinfecting, they should be disinfected and kept in the room or anteroom. Be sure that are instructed in the proper use of personal protective equipment including safe removal to prevent contaminating themselves or others in the process, and that contaminated equipment is disposed of appropriately ….

Environmental Protection Agency-registered hospital disinfectant with a label claim for a non- enveloped virus e. Although there are no products with specific label claims against the Ebola virus, enveloped viruses such as Ebola are susceptible to a broad range of hospital disinfectants used to disinfect hard, non-porous surfaces. In contrast, non-enveloped viruses are more resistant to disinfectants. As a precaution, selection of a disinfectant product with a higher potency than what is normally required for an enveloped virus is being recommended at this time.

EPA-registered hospital disinfectants with label claims against non-enveloped viruses e. The means of disinfection that are reported of common use in West Africa at the moment include copious drenching with bleach. It has now come to light that the majority of health care workers worldwide do not have sufficient training in the PPE and disinfection protocols that EBOV contamination requires. Most hospitals in the US are reported not to have in stock the appropriate materials to ensure the safety of the nursing and medical staff. Taken together, this fluid situation contributes to the state of heightened alert, concern and anxiety among professionals and the general population.

By the 6th of October , the first case contracted on European soil was reported in Madrid, Spain: Teresa Romero, a doctor who had been caring for two missionary priests who had just died of Ebola in Madrid. This was the first case of Ebola diagnosed outside of the African continent. He had assisted a pregnant woman, apparently Ebola-negative that is, showing no fever or other EVD symptoms as per the reports of her family and community healthcare personnel at the time.

She had collapsed due to excessive pre-partum bleeding on a street in Liberia on the 18th of September.

  1. Desirees Double Entry Sex Secrets.
  2. Search form.
  3. Travels with Puff: A Gentle Game of Life and Death!
  4. Review ARTICLE.
  5. Neoliberal Ebola.
  6. Conditions of Identity: A Study in Identity and Survival.
  7. Download Neoliberal Ebola: Modeling Disease Emergence From Finance To Forest And Farm 2016!

On the 20th of September, Mr. Duncan had returned to the US. A few days later the woman gave birth to an apparently healthy baby, albeit premature by a few weeks. According to official Liberian reports, neither mother nor infant had confirmed EVD; but, the popular press had drawn the association of Mr. On the 24th of September, following his arrival in the US, Mr. Duncan developed the first symptoms of incipient fever. Two of the nurses who cared for Mr. They both were successfully cured from the disease.

Assuming no change in the control measures for the present epidemic, the cumulative reported numbers predict an exponential growth of the epidemic, along with atrociously high numbers of Ebola-infected and Ebola fatalities by early On the basis of the initial periods of exponential growth, the estimated basic reproduction numbers R 0 have been reported to be 1. The estimated current reproduction numbers R are 1. Therefore, the corresponding doubling times were derived to be These data suggest that different mutations of the Zaire species may characterize each of the three fulcrum countries.

If molecular analyses should confirm this hypothesis, the difficulty and complexity to raise an effective vaccine would considerably increase. As things stand, CDC reports that, at the very best, an effective vaccine against EBOV could not be ready, tested and validated before early Ebola is the headstream of the Mongala River, a tributary of the Congo River.


Along these banks, the Ebola virus was first discovered in the mid seventies. By the international community came together to simplify the nomenclature, and changed its name to Ebola virus EBOV, ebolavirus. The genus ebolavirus, closely related to the Marburg virus, belongs to the negative strand RNA family of Filoviridae , order Mononegavirales. As such, purified RNA of a negative-sense virus is not infectious by itself as it needs to be transcribed into positive-sense RNA, although each virion can be transcribed to several positive-sense infectious RNAs.

This property raises the difficulty in producing effective vaccines. It must also be noted that errors during reverse transcription are embedded into both strands of the intermediate viral DNA before integration into the host DNA, which can cause changes in the transcription-translation of the host cell functional household protein constituents, and consequential significant alterations in the host cell structure and function in its natural micro-environmental milieu. In the case of EBOV, the virus infects the myeloid population, and it is to be expected that EBOV-infected macrophages and dendritic cells may have structural and functional alterations that may impair their role in cell-mediated immunity and antigen presentation vide infra.

The five known species of EBOV are named for the region where each was originally identified:. On the 20th of February , the Uganda Ministry officially announced the end of the epidemic in Bundibugyo, with the last infected person discharged on the 8th of January Reston virus: Reston EBOV was discovered during an outbreak of simian hemorrhagic fever virus in crab-eating macaques from Hazleton Laboratories now Covance in Since the initial outbreak in Reston, Virginia, it has since been found in nonhuman primates in Pennsylvania, Texas, and Siena, Italy.

In all cases, the affected animals had been imported from a facility in the Philippines, where the virus has also infected pigs. It is the only ebolavirus that is pathogenic for nonhuman primates, and that is nor originally endogenous to Africa. It is now thought that this species broke out first amongst cotton factory workers in Nzara, Sudan today South Sudan. The first case reported was a worker exposed to a potential natural reservoir, although the original carrier remains unknown.

The most recent outbreak occurred in August, , when 13 cases were reported in Djera, Democratic Republic of Congo. Necropsies showed blood within the heart to be brown; no obvious marks were seen on the organs; and one necropsy displayed lungs filled with blood. Ferric hemoglobin has increased affinity for oxygen but reduced ability of the red blood cell to release oxygen to tissues, compared to the normal ferrous hemoglobin. Consequently, methemoglobin concentration is elevated, the blood appears oxidized and acquires a deep red-to-brown color, and tissue hypoxia occurs. Hemoglobin is also found in non-blood tissues and cells, such as neurons and macrophages, where its function is primarily that of an anti-oxidant.

At high concentrations of methemoglobin, that anti-oxidant protective ability is lost, placing both neurons and myeloid cells at higher risk of programmed cell death i. In that form, it re-enters the mitochondria and becomes protoporphyrin. Protoporphyrin combines with iron to form the heme, which now exits the mitochondria to combine with the globin molecule produced in the ribosome.

Studies of tissues taken from the chimpanzees showed results similar to human cases during the Ebola outbreaks in Zaire and Sudan. As more dead chimpanzees were discovered, many tested positive for Ebola using molecular techniques. The source of the virus was traced to infected western red colobus monkeys Procolobus badius upon which the chimpanzees preyed. Zaire virus: Zaire EBOV is the type reference for all species of Ebola virus, since it has a sole known member - although it is suspected to have the potential for several mutant forms. Zaire EBOV is responsible for the largest number of outbreaks of the five known members of the genus , including both the first documented outbreak in , and the current most deadly outbreak.

Originally, the symptoms were mistaken for malaria, and the patients received quinine, with unsuccessful outcomes. The natural reservoir host of Ebola virus remains unknown. However, on the basis of evidence and the nature of similar viruses, EBOV is believed to be animal-borne and that bats are the most likely reservoir.

Four of the five virus strains occur in an animal host native to Africa. Fruit bats of the Pteropodidae family are the most likely natural ebolavirus hosts. Bats and other wild animals drop partially eaten fruits and pulp, and land mammals may feed on these fallen fruits, thus initiating the EBOV-infected food chain that leads to human consumption. In brief, it is believed that Ebola is introduced into the human population through close contact with the blood, secretions, organs and other bodily fluids of infected animals such as the fruit bats, chimpanzees, gorillas and other monkeys, forest antelope and porcupines, which all have been found ill or dead with signs akin to EVD in the rainforest.

Fruit production, animal behavior, as well as other indigenous factors of sub-tropical Africa that vary from year to year and in different seasons and places may contribute to trigger outbreaks of the different EBOV species among animal populations and humans, although no clear corollary relationships have been uncovered to be predictive of Ebola outbreaks [ 1 , 2 ]. Whereas EBOV is acquired upon contact with blood or bodily fluids of infected animals, it is then thought to spread through human-to-human transmission only via direct contact through broken skin or mucous membranes with blood, secretions, or other bodily fluids of infected people, and possibly with surfaces and materials e.

In addition, traditional caregiving, which may engage physical contact and touching, and burial ceremonies during which mourners have direct contact with the body of the deceased person are thought to play an important role in the transmission of Ebola vide infra [ 1 ]. At this time, and based on the epidemiological patterns of previous outbreaks, it is not believed that the virus can be contracted by aerosol, although the specter of mutated EBOV that could be airborne is a distinct possibility, if not a statistical probability.

The aggressive nature of the outbreak presently in course seems to suggest that the current species of EBOV may in fact already have mutated and evolved into a more virulent form than originally expected, with contagion potential beyond exposure to body fluids of patients actively showing symptoms, as Richard E. The contributions of environmental factors to EBOV transmission are not fully understood to this date.

Use only a mattress and pillow with plastic or other covering that fluids sic cannot get through. Do not place patients with suspected or confirmed Ebola virus infection in carpeted rooms and remove all upholstered furniture and decorative curtains from patient rooms before use. In fact, the rationale for this position, strictly on immunopathological grounds is unclear at best and at worst categorically unfounded. The statement is apparently based on the findings obtained from the previous outbreaks. Nonetheless, scant data are available to generate statistical inference of sufficient power to warrant such assertion.

In brief, it is possible, or at least not improbable, based on biological and statistical evaluation of the evidence, that EBOV is contagious well before symptoms are noted. This, in and of itself, may contribute to explain why the current outbreak is aggressively advancing beyond our comprehension and expectation.

Based on the observations gathered during the previous outbreaks, it is believed that EBOV is sensitive to heat and chemical denaturation. But supportive evidence across the recognized EBOV species is not compelling to this date. Evidence suggests, by contrast, that EBOV may have remarkable resistance.

To cleanse EBOV-contaminated requires extensive washing with chlorine and ethanol diluted in clean uncontaminated water i.

  • Behavioral Neuroendocrinology.
  • Download Neoliberal Ebola: Modeling Disease Emergence From Finance To Forest And Farm 2016;
  • Browse more videos;
  • It is in part for these reasons, that the dearth of clean water remains a critical impediment in slowing the outbreak and bringing about an effective medical response in West Africa [ 6 , 7 ]. Quarantine, which is nothing but enforced isolation, is currently the most effective mode of decreasing the spread of this disease.

    Neoliberal Ebola Modeling Disease Emergence from Finance to Forest and Farm

    Households, schools, localities, villages, town, cities or entire regions may be lawfully isolated where the disease is occurring or believed to occur, or individuals putatively infected may frequent. Contact tracing is an important approach, perhaps one of the most effective public health protocols to contain an outbreak. Contact tracing permits to find everyone who has had close contact with infected individuals and watching for signs of illness.

    If any of these contacts come down with the disease, they should be isolated, tested, and treated, and their contacts traced and followed. It is clear that contact tracing is feasible and efficient only when the number of cases is small or limited; as an epidemic grows, contact tracing evidently takes an increasingly prohibitive amount of time and manpower to run. Symptoms of Ebola can start 2—21 days following initial contact with the virus.

    Initial manifestations include a sharp rise in fever, sore throat, muscle pain and headaches. Explosive vomiting and diarrhea soon follow, which, if left untreated, lead to serious dehydration, dizziness, confusion, kidney and liver failure, and eventually complete physiological collapse. Skin rash and eruptions appear, which soon develop into bleeding infected ulcerations. Extensive internal and external bleeding from the orifices i. Laboratory findings confirm low white blood cell and platelet counts, and elevated liver enzymes. The general symptomatic profile of EVD resembles that of other viral hemorrhagic fever VHF diseases [ 6 , 8 - 10 ], including dengue Chiappelli et al.

    Consequently, the diagnosis for EVD can be complicated and relatively slow, because several of its symptoms overlap with malaria, cholera, dengue, and other VHFs. Expectations are, in fact, that, as the present Ebola epidemic continues to grow, it may eventually shut down malaria and dengue control efforts on the African continent.

    Case in point, the present outbreak has virtually hampered malaria control efforts in Liberia, Guinea and Sierra Leone, raising fears that cases of the mosquito-borne illness will soon rise because routine health care in the affected countries has all but collapsed Thomas Teuscher, acting executive director of Roll Back Malaria Partnership. As a result, and in part because the early symptoms of Ebola mimic the symptoms of malaria, tens of thousands of people are erroneously be given antimalarial medication, which can induce drug resistance to the parasite that causes the disease in malaria-free individuals, and deplete the available doses of anti-malaria medicine.

    Patients with severe hemorrhagic disease, such as Ebola or dengue produce dangerously high levels of inflammatory cytokines, which destroy normal tissue and microcirculation, leading to profound capillary leakage, renal failure, and disseminated intravascular coagulation. However, the use of this technology is often not feasible on the ground and in field hospitals of isolated villages or localities of West Africa. Confirmation of EBOV infection can also be obtained by electron microscopy, and virus isolation by cell culture [ 1 ].

    To confirm Ebola cases, samples must be shipped to a testing site; however, considering the high infectivity of these samples, shipping operations such as these are of very high risk. Genomic and proteomic advances now proffer some degree of understanding of the EBOV virion. Data propose a minimal gene set that can distinguish between EVD survivor and non-survivor non-human primate experimental animals under specific anticoagulant treatment conditions. In a recent study of 23 rhesus macaques: 19 treated with anticoagulant therapeutics 11 with recombinant human activated protein C, and eight with recombinant nematode anticoagulant protein — of these animals, four of the treated, two in each group, survived a lethal challenge with EBOV [H.

    Specifically, the data pointed to:. Whereas administration of lactoferrin has been shown to be beneficial in reestablishing physiological homeostasis of iron metabolism in an experimental model of hemorrhagic disease in rodents [ 15 ], the putative palliative role of lactoferrin administration in hemorrhagic EVD remains to be examined. Testing of miravirsen, as an experimental RNA therapy, in EBOV-infected patients, albeit seemingly promising [ 19 ], has not commenced as of this date.

    Specific analysis of the identified genes suggested that genes associated with cellular immune and inflammatory responses were up-regulated in non-survivors, consistent with the hypothesis that non-survivors experience acute deregulation of cellular immune surveillance [ 13 ] vide infra. It is possible and even probable that future investigation of these pathways could reveal transcriptional signatures specific to EBOV infection and host immune response. Rather than the more invasive technique of collecting blood for measuring EBOV, saliva was established in earlier studies to be potentially useful and promising for the investigation of Ebola epidemics and pandemics.

    In those studies, anti-EBOV immunoglobulin G antibodies could not be detected in the saliva of patients who had elevated levels of serum anti-EBOV immunoglobulin G antibodies by enzyme-linked immunosorbent assay. Transcriptomic analysis of the type described above must now be performed on salivary samples, in order to maximize utilization of this body fluid for the purpose of fast, sensitive and reliable diagnosis EBOV infection. For the time being, no specific treatment for EVD disease is available, in part because of the complex, multi-step and highly orchestrated path of internalization and fusion of the Ebola virus.

    Upon receptor binding, the virus is internalized into endosomes primarily via macro-pinocytosis. The acidified endosomal cellular proteases Cathepsin L and B cleave GP 1,2 , and expose residues in the receptor binding site. That the drug ezetimibe blocks Niemann Pick C1 like protein [ 20 ] seems to suggest that it might well contribute to blunt productive EBOV infection.

    However, this treatment option has not been examined in EVD patients at this time. Certain novel drugs are undergoing testing, such as the human immunodeficiency virus-inactivating protein cyanovirin-N, which binds to vGP1,2, and inhibits infectivity of Ebola virus [ 21 , 22 ].

    There are certain requirements that must be met when attempting to prevent EVD epidemics to burgeon into a pandemic threat, and which can be summarized as follows:. Human-to-human transmission can occur via direct contact with blood or bodily fluids from an infected person, including touching during caregiving, embalming of an infected dead person, contact with the corpse during burial, or handling personal objects of the Ebola victim contaminated by the virus, particularly bedding, clothing, needles and syringes [ 28 ].

    Many emerging pathogens are generating antibiotic resistance, and some are multi-drug resistant. Most pathogens in humans are zoonotic in origin. Population, ecological, and behavioral alterations that increase contact with wildlife intensify the emergence of these pathogens. Anthropogenic environmental modification has altered the risk of zoonotic infection from wildlife. Ebola exemplifies how anthropogenic factors facilitate pathogen transmission between human and nonhuman animal populations [ 31 ].

    The increasing populations of domestic animals, especially in feedlots, with close and constant contact with wildlife contribute to transmission. As a result, many wildlife species are reservoirs of pathogens that threaten the health of domestic animals and humans. Disease emergence most frequently results from a change of ecology of host and pathogen, or both. Human population expansion has driven the emergence of EIDs through increasing population density, especially in urban areas, and encroachment in to wildlife habitat.

    Human encroachment on shrinking wildlife habitat has also caused increased wildlife population densities and the emergence of wildlife EIDs. Understanding how environmental change alters the contact between human and non-human primates, thereby increasing the possibility of sharing infectious diseases detrimental to humans or nonhuman primates, is essential to global health planning. Diseases like Ebola devastate both human and wildlife communities, with outbreaks of the virus tracing their origins to zoonotic transmissions from local apes, especially since monkeys and apes often share parasites with humans [ 33 ].

    However, human displacements of fruit bats through deforestation make this a vector species for transmission of Ebola, as well. EIDs, such as Ebola, which have the highest fatality rates, have emerged from wildlife. Moreover, the causes of their emergence are clearly linked to the way in which humans interact with wildlife, through encroachment, road building, deforestation, hunting and the global trade in them.

    The recent interest in the underlying causes of zoonotic disease emergence, namely changes to human demography, behavior and the environment, denotes a shift in tropical medicine, from reactive to proactive approaches. Through this perspective, human—animal entanglements are viewed in terms of the social production of space to understand viral movement by elaborating the circumstances through which viruses, humans, objects, and animals come into contact.

    Anthropological studies in these hotspots aim at understanding local views and responses to an outbreak. In experiencing Ebola, local people employ multiple explanatory models to make sense of and respond to the outbreak; their indigenous epidemic control measures are often implemented and these are consistent with the ones being promoted by healthcare workers; although some cultural practices, such as burial practices, amplify the outbreak [ 37 ]. How local people in Gabon viewed Ebola and responded to the rapid killer during outbreaks in the s, and how they view the international health care worker teams mobilized to help control the disease are key concerns in understanding subsequent outbreaks [ 38 ].

    The fear of being infected with Ebola and the desire to flee the area are human universals. Local people in village communities invoked sorcery and consulted indigenous healers as they attempted to understand and explain the disease. Local people also worked to help control the outbreak by isolating infected people or limiting their contacts, kept children away from the sick, and sought treatment from indigenous healers and government health care workers.

    Efforts to control high mortality diseases, such as Ebola, provide two distinct but complementary interventions during the first phases of an outbreak in the Republic of Congo [ 39 ]. The experiences of health care workers during Ebola outbreaks in Uganda in —, Republic of the Congo in , and Democratic Republic of the Congo in included: a lack of protective gear, basic equipment, and other resources necessary to provide care, especially during the early phases of the outbreaks; and stigmatization by family, coworkers, and community [ 40 ].

    Improving treatment of VHFs in sub-Saharan Africa ultimately hinges on effective and compassionate care for the effected patient. To this end, there is the need to refocus efforts on aggressive supportive care and clinical monitoring; including communications and social mobilization experts as a primary part of every outbreak response team; and reestablishing the isolation ward as the key functional component of the overall outbreak control strategy [ 41 ].

    The key lesson learned is that containment of the Angolan epidemic depended on the collaboration of the affected community; a critical factor being active involvement of all stakeholders at the start of the outbreak response. Key themes were:. VHF outbreaks in Africa can be seen as a paradigm for ethical issues posed by epidemic emergencies, including isolation and quarantine; privacy and confidentiality; and the interpretation of ethical norms across different ethnocultural settings, especially research ethics [ 44 ].

    While informed consent and institutional review processes governing collection of biological samples and epidemiological data are regulated by national guidelines and international conventions, there remains a need for new ethical frameworks on behalf of engaging potentially affected communities in research design and in the community permission process during an outbreak. Hence, zoonotic diseases afford an opportunity to pose scientific and policy challenges optimally met by complex modeling approaches of epidemiological, ecological and social processes.

    Ebola, especially because of the fear of widespread contagion and death, provides a way to understand how the social and political lives of a zoonotic disease model can be co-constructed, scientifically and politically, with particular policy interests in mind. Regarding the interplay of culture and ecology in the epidemiology of infectious disease, behaviors related to diet, activity patterns, water use, and sexual practices that predispose individuals to certain diseases might be shaped by culture [ 48 ], p.

    While cultural practices, including agriculture and warfare, provide the means for people to actively transform their environments, these can also affect their susceptibility to infections. Cultural models of etiology, patient role and treatment influence how people respond to the illness [ 48 ], p. Human biosocial factors clearly have an impact on R0, the basic reproductive rate of a pathogen, or the expected number of infections caused by one infected individual in a susceptible population.

    Social relationship patterns drive contact rates, and are themselves related to norms of social affiliation. Only by considering both the activities of the state and the behaviors of the pathogen, in other words bringing together the macro- and micro-levels of analysis, can we understand an infectious disease like Ebola. The intersection of national security and public health in recent decades has brought about a reframing of the threat of infectious disease, from prevention to preparedness [ 54 ].

    The norm of preparedness, used throughout the post-war decades in military and civil defense contexts, has migrated to governmental public health intervention. With this move, widespread public discussion of biological threats has focused on expert techniques, such as the scenario-based exercise, which serve to generate both a sense of urgency, absent the event itself, and knowledge about vulnerabilities in response capability, on behalf of intervention design. These trends impact health ministries, as they interact with bilateral and non-governmental aid organizations, often through public-private partnerships.

    The resulting mandated managerial mechanisms to track funds, together with monitoring and evaluation protocols, are indicative of broad neoliberal reforms in the global health sector. Ebola hemorrhagic fever is a severe viral infection with fulminating pathology characterized by fever, shock and coagulation defects.

    Endothelial cells, macrophages, monocytes, and liver cells are the main targets of infection. Following infection by the virus, a secreted glycoprotein sGP known as the Ebola virus glycoprotein GP is synthesized. Ebola replication overwhelms protein synthesis of infected cells and host immune defenses. The GP forms a trimeric complex, which binds the virus to the endothelial cells lining the interior surface of blood vessels.

    The sGP forms a dimeric protein that interferes with the signaling of neutrophils, allowing the virus to evade the immune system by inhibiting early steps of neutrophil activation. Neutrophils also serve as carriers to transport the virus throughout the entire body to places such as the lymph nodes, liver, lungs, and spleen [ 57 ]. EBOV infects dendritic cells, which in turn disables the interferon system and disrupts henceforth the host antiviral immune surveillance response [ 58 , 59 ].

    Almost contemporaneously, the virus targets myeloid cells i. The virus operates in a sequential fashion by first disabling the immune system, then the vascular system, during which observed symptoms can include hemorrhage, hypotension, drop in blood pressure, and catastrophic organ failure. These symptoms are usually followed by shock and death. After infection, IL10 levels were significantly elevated at the earliest times of infection in pediatric patients who died.

    The role of IL10 in inhibiting antigen-stimulated T cell proliferation supports the assumption that a T cell—mediated response is critical for survival during EVD. Levels of soluble intracellular adhesion molecule sICAM 1, and soluble vascular cell adhesion molecule sVCAM 1 for children are normally higher than for adults, and the levels that reported in surviving pediatric patients were consistent with these normal levels. Pediatric patients who died had sICAM and sVCAM levels 2—3 times above the reference range 0—10 days after symptom onset, but these levels dropped to within the reference range at 11—15 days.

    This pattern may reflect early excessive, and ultimately detrimental, endothelial activation in these patients. Consistent with this hypothesis are the increased plasminogen activator inhibitor 1 PAI-1 levels also seen in pediatric patients who died; endothelial cells in response to activating cytokines release PAI However, adult patients typically do not seem to be affected by this phenomenon.

    Elevated PAI-1 levels in pediatric patients with hemorrhagic manifestations likely represent the overactive endothelium and not a functional inhibition of fibrinolysis, since PAI-1 activity is likely to be low, as it rapidly converts to the inactive form under physiologic conditions. In brief, Ebola-surviving pediatric patients tend to have higher levels of the chemokine regulated on activation, normal T cell express and secrete marker and lower levels of PAI-1, soluble intracellular adhesion molecule, and soluble vascular cell adhesion molecule than pediatric patients who died.

    Adult patients had similar levels of these analytes regardless of outcome [ 59 , 60 ]. EBOV infection includes symptoms such as headache, encephalitis, meningitis, cerebral edema, and seizures, which indicate the virus involvement in pathology of the central nervous system CNS. Owing to the high mortality rates associated with Ebola virus infection, studies of the long-term neurological and neurocognitive effects are virtually non-existent.

    Nevertheless, news reports have suggested that EBOV-survivors continue to experience complications such as headache, weakness, fatigue, sensory changes, and inflammation of certain organs. While there is evidence to suspect CNS complications among survivors, this may go unrecognized or unreported [ 61 ].

    Considering our current knowledge of Ebola viral mechanisms, reported complications from long-term survivors, and knowledge of the adverse effects of pro-inflammatory cytokines on neuronal function, three potential contributors to ongoing CNS dysfunction in EBOV survivors are considered below:. While transient innate immune responses in the form of cytokines are beneficial to the host, the same essential spectrum of cytokines leads to deregulation of homeostatic mechanisms, destruction of host tissues and apoptosis [ 63 ].

    Recommended for you

    Cytokines have both atherogenic and prothrombotic effects, which may directly influence neurological events such as ischemic stroke or vascular dementia. EBOV produces coagulation defects via cytokine production that directly influence the coagulation cascade. Abnormalities of the brain coagulation system have been implicated in traumatic brain injury [ 66 ]. IL6 plays a critical role in adult neurogenesis [ 70 ], which is altered in many neuropathological situations like stroke, status epilepticus , mechanical damage, and Alzheimer, Parkinson and Huntington diseases, which all share inflammation in common [ 71 , 72 ].

    IL6 has been thought to exert neurotrophic effects by preventing oxidative stress and apoptosis. This affects cognitive processes such as learning and memory [ 75 , 76 ], sleep [ 77 ], food and water intake [ 78 ]. Hence inflammation, mediated in part by chemokine activity and the release of proinflammatory cytokines, contributes to the breakdown of the brain microvascular endothelial cells that constitute the BBB Barkhordarian et al.

    While most studies have focused on the inflammatory response of microglia and astrocytes [ 89 - 91 ], perivascular cells also play a key role in brain inflammation [ 92 ]. CNS pericytes are involved in recruitment of peripheral cells to the brain, which may directly produce neuronal damage or promote microglial inflammation [ 93 , 94 ]. The BBB separates the brain from the circulatory system and protects the central nervous system from potentially harmful chemicals while regulating transport of essential molecules and maintaining a stable environment [ 95 , 96 ].

    Specialized endothelial cells that line brain capillaries and transduce signals from the vascular system and brain form its structure. Both the structure and function of the BBB is dependent upon the complex interplay between the different cell types such as the endothelial cells, astrocytes, and pericytes , and the extracellular matrix of the brain and blood flow in the capillaries [ 97 ].

    Three sites have been identified with a physical barrier via tight junctions that include the brain endothelium forming the BBB , the arachnoid epithelium forming the middle layer of the meninges , and the choroid plexus epithelium, which secretes CSF [ 91 ]. The BBB contains specialized endothelial cells that are attached through tight junctions and adherence junctions, which function to separate the CNS from the circulation and restrict and prevent blood-borne molecules and peripheral cells from entering the CNS [ 98 ]. Experimental studies of human cultured embryonic cells have demonstrated that virus-like particles VLPs consisting of the Ebola virus matrix protein VP40 and GP1,2 activated endothelial cells and disrupted barrier function.

    Other viruses, including the Human Immunodeficiency Virus HIV , produce viral proteins such as gp, Tat, and Nef released from infected cells, which lead to increased expression of adhesion molecules such as intercellular adhesion molecule ICAM -1 and endothelial adhesion molecule [ ]. These molecules facilitate the transport of HIV within these infected macrophages by promoting their ability to bind and migrate across the BBB, although cell-free virions are also thought to be able to cross the BBB due to changes in tight-junction formation [ , ].

    In , cases of hemorrhagic fever occurred in Marburg. The Marburg virus MBGV and EBOV, as noted above, are both members of the family Filoviridae , and are very similar in terms of morphology, genome organization, and protein composition [ ]. The pathology of Marburg disease was investigated from gathering tissues from brain, spleen and liver from those infected and have been used to make inferences about the pathology of Ebola virus. Brain tissue derived from those infected with the Marburg virus were noted for brain swelling, increases in vascular permeability, associated reduced effective circulating blood volume, and interstitial edema in the brain.

    The pathologic alterations found in Ebola virus infection appear to share similar features to those found in Marburg virus infection, though an absence of comprehensive comparative studies remain. EBOV has been found to infect the meninges. Most viral infections that involve the meninges can manifest into progressive neurologic disorders.

    Clinical findings reflect disease progression and the specific areas of CNS involvement, which is determined by viral tropism [ ]. For example, polioviruses preferentially infect motor neurons, mumps infects epithelial cells of the choroid plexus [ ]; however, the tropism of filoviruses remain unclear [ ]. Encephalitis due to infection, post-infections encephalomyelitis which may occur after measles or Nipah virus encephalitis and conditions such as post-poliomyelitis syndrome, which some believe is a persistent manifestation of poliovirus infection, are examples of neurological syndromes that can occur with Ebola virus invasion.

    Symptoms that signal encephalitis due to infection of the meninges include sudden fever, headache, vomiting, heightened sensitivity to light, stiff neck and back, confusion and impaired judgment, drowsiness, weak muscles, a clumsy and unsteady gait, and irritability. Symptoms that require emergency treatment include loss of consciousness, seizures, muscle weakness, or sudden severe dementia.

    Chronic meningitis from Cryptococcus usually develops among patients with compromised immune systems e. CT or MRI is usually recommended first, before the lumbar puncture [ ]. Encephalitis and meningitis can cause cerebral edema, and cerebral edema among those infected with Ebola virus has been reported.

    Swelling can disrupt oxygen supply as the blood vessels become squeezed. Cerebral edema is a medical emergency that can even lead to death as brain cells become damaged and die. Global cerebral edema is a powerful and consistent predictor of cognitive dysfunction [ ]. However, determining the long-term cognitive consequences of these cases are rare, as they are often associated with high mortality rates.

    In brief, while the research on the direct effects of EBOV on CNS is limited, we can only draw from knowledge about viral entry, viral propagation, and multiple organ failure about the potentially profound effects on the central nervous system.

    Survivors are at increased risk for cognitive impairments. As with most neurological conditions, prognosis for cognitive outcomes will be based upon the timing between infection, diagnosis, and treatment. Infection with EBOV leads to aggressive and highly lethal hemorrhagic fever in humans. Its virulence is associated with a variety of processes and events that engage, and subsequently blunt cellular immune surveillance. Initial immune responses include a rapid rise in pro-inflammatory cytokines e.

    Soon into the immune surveillance response, which commences immediately after infection, a slower process on cellular pathology ensues, which includes myeloid cell and endothelial cell infection and cytopathology. Consequential to this second phase are both a sharp rise in fever, and loss in vascular integrity, which leads to increased permeability of blood vessels with transudates increasingly rich in micronutrients, red blood cells and eventually white blood cells.

    In brief, EBOV actively subverts both innate and adaptive immune responses, and triggers harmful inflammatory responses that inflict direct tissue damage.

    Ebola Reston

    The organism is ultimately overwhelmed by a combination of inflammatory factors and virus-induced cell damage, particularly in the vasculature, often leading to death from liver and kidney failure, complicated by septic shock [ ]. The filoviridae family of viruses, including EBOV, causes severe impairment of innate and adaptive antiviral cellular immune responses, in part as a result of virally encoded immune antagonists, which render the host incapable of mounting effective innate or adaptive immune responses.

    The exact requirements for immunity against EBOV infection are poorly defined at this time. The transfer of both serum and splenocytes, but not serum or splenocytes alone, from eVLP-vaccinated mice conferred protection against lethal EBOV infection in these studies. In brief, the first telling symptoms of incipient EVD include high fever and bleeding from the orifices. As dendritic cells and macrophages succumb to EBOV infection, the cellular immune surveillance mechanism is progressively impaired, and virus titter rises, as does EBOV-caused cyto-and physiopathology. Immune evasion events of EBOV include:.

    It is possible and even probable that EBOV-infected dendritic cells and macrophages soon invade specific organs, and establish themselves as EBOV-infected resident myeloid cells. Case in point, renal myeloid cells represent a constitutive, extensive and contiguous network of local immunity cells that provide sentinel immune surveillance.

    They contribute to induce and regulate inflammatory responses to protect the kidney from infection. They are a perfect example of local immunity, as similar sentinel myeloid cells are found in every organ to play key factors in the initiation and propagation of renal disease, as well as essential contributors to subsequent tissue regeneration, regardless of etiological and pathogenesis mechanisms [ ]. Indeed, dendritic cells and macrophages, in part because of their high degree of motility, play a critical role in the cross-talk between systemic and local immunity, including between the central nervous system and mucosal immunity — that aspect of local immunity is most likely to be severely affected during EBOV infection.

    More generally speaking, HIV can escape from systemic immunity assessments simply by becoming hidden in macrophages and dendritic cells that transmigrate from the systemic compartment to organs and lymph nodes, such that lymphadenopathy is a clinically relevant sign and important guiding tools for detecting hidden HIV in asymptomatic individuals [ , ]. Like many other infections, EBOV induces massive lymphocyte apoptosis, which is thought to prevent the development of a functional adaptive immune response.

    CD44 is a cell-surface glycoprotein involved in cell—cell interactions, cell adhesion and migration. In many instances, this event is accompanied by a dramatic rebound of lymphocyte numbers in the blood, which however appear to be apoptotic lymphocytes, suggesting that local i. Data have indeed shown that, despite significant lymphocyte apoptosis, a functional and specific, albeit insufficient, adaptive immune response is made in lethal EBOV infection and could be protective upon transfer to naive infected recipients.

    EBOV infection induces massive lymphoid and myeloid apoptosis. Data have established that EBOV-induced lymphocyte apoptosis in vivo occurs via both the death receptor extrinsic and mitochondrial intrinsic pathways. Inhibiting lymphocyte apoptosis during EBOV infection fails to improve animal survival rates [ ], indicating that the immunopathogenesis induced by EBOV occurs upstream from T cell activation.

    Neoliberal Ebola: modeling disease emergence from finance to forest and farm.

    The hypothetical model we propose here is grounded on our current understanding that costimulatory signals, such as CD28 and ICOS are critical for the establishment and maintenance of systemic and local cellular and humoral immune surveillance, and rests on previous observations in a related model that demonstrated that the impairment in the B7 family-ligand costimulatory pathways may promote tumor immune evasion by providing a negative regulatory signal equivalent to T cell apoptotic cell death [ ].

    Indeed, this paradigm has led to the development of a variety of immunotherapies targeting costimulation pathways [ - ]. Currently the diagnosis of Ebola is difficult [ 61 , , ], and there are no specific vaccines or medicines such as antiviral drug that have been proven to be effective against Ebola. Symptoms of Ebola are treated as they appear. The following basic interventions, when used early, can significantly improve the chances of survival:.

    Timely treatment of EVD is important but challenging since the disease is difficult to diagnose clinically in the early stages of infection. Because early symptoms such as headache and fever are not specific to ebolaviruses, cases of Ebola may be initially misdiagnosed, as noted above [ ]. We discussed elsewhere the main difficulties in developing vaccines for HIV [ ]. Using mRNA extracted from bone marrow of Ebola survivors, human monoclonal antibodies against Ebola virus surface protein have been experimentally produced and now raise the hope for the development of a safe vaccine [ ].