BiotechStockTrader has partnered with BCC Research to bring you a look at the history of pandemic outbreaks and the effect they have globally. Posted below is a summary of the research report, available in full from BCC Research.
Current and Potential Pandemics
Notable current pandemics include HIV/AIDS, HBV, HCV, TB and malaria. The H1N1 virus, if it continues to mutate and spread, could present itself as a pandemic, as it did in 2009.
Infectious diseases that could become pandemics include viral hemorrhagic fevers such as Lassa fever, Rift Valley fever, Marburg virus, Ebola virus and Bolivian hemorrhagic fever.
Influenza (particularly H1N1), H5N1 (avian flu), severe acute respiratory syndrome (SARS) and Middle Eastern respiratory syndrome could also become pandemic again in the future.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes COVID-19. The pandemic is the greatest public health challenge since the 1918 influenza pandemic and the biggest threat to destabilizing the global economy since World War II.
H1N1 Influenza (Swine Influenza)
H1N1 swine flu is a subtype of influenza A virus (a transmissible viral disease) that triggers upper and potentially lower respiratory tract infections in the host that it infects, producing symptoms such as nasal secretions, chills, cough, reduced appetite, and probably lower respiratory tract disease. Because H1N1 swine influenza is a widespread infection in pigs worldwide, it also is called H1N1 swine flu. H1N1 swine flu contributes to respiratory illness and may affect the pig’s respiratory tract. Sometimes, people who are closely associated with pigs or in the proximity of pigs have developed swine flu (zoonotic swine flu).
The H1N1 influenza virus is an orthomyxovirus, developing 80-120 nm-diameter virions with an RNA genome size of around 13.5 kb. The swine influenza genome has eight distinct segmented regions and encodes 11 different proteins:
- Envelope proteins hemagglutinin (HA) and neuraminidase (NA).
- Viral RNA polymerases which include PB2, PB1, PB1-F2, PA, and PB.
- Matrix proteins M1 and M2.
- Nonstructural proteins NS1 and NS2, which are crucial for efficient pathogenesis and viral replication.
U.S. researchers first isolated swine flu from pigs in the 1930s. Eventually, pork producers and veterinarians worldwide recognized it as a cause of influenza infections in pigs. H1N1 was the predominant swine influenza strain for the next 60 years. Unfortunately, there also is the risk of cross-species transmission of the influenza viruses due to the potential for genetic variability in the swine flu virus. Investigators concluded that the “2009 swine flu” strain originating in Mexico was known as novel H1N1 flu because it was found mainly to infect humans and exhibits two major surface antigens, type 1 hemagglutinin, and type 1 neuraminidase. In the novel H1N1 flu, the eight RNA strands have one strand from human flu strains, two from avian (bird) strains and five from swine strains. The CDC estimated during the 2009 pandemic 43-89 million cases of swine flu were reported over a one-year period, with 1,799 deaths in 178 countries worldwide.
Prevention of Human-to-Human Transmission
The main route of swine flu virus transmission among humans occurs when someone infected sneezes or coughs and the virus reaches a mucous surface of another person. Or, when someone infected with the virus touches their own nose, mouth and surrounding areas. Swine flu is most contagious in people during their first five days of illness, but this can rise in children and in the elderly. Current CDC guidelines for preventing the spread of the virus include regular handwashing with soap and water or alcohol-based sanitizers, and also disinfecting home, hospital, and public settings by brushing with a diluted bleach solution. Anyone living in an area where the disease is widespread and suspecting an illness or experiencing flu-like symptoms should avoid the workplace and public transportation, and see a doctor immediately.
Ebola Virus Disease
Ebola viruses are pathogenic agents in man and great apes associated with a severe, potentially fatal, systemic disease. In West or Equatorial Africa, four species of ebola viruses are described. When the more virulent types enter the human population, transmission occurs mainly through interaction with contaminated body fluids and can lead to major epidemics. Such viruses cause a disease characterized by widespread viral replication, immune suppression, irregular inflammatory responses, severe loss of fluids and electrolytes, and high mortality rates.
Ebolaviruses belong in the order Mononegavirales to the genus Ebolavirus of the family Filoviridae, viruses whose genome consists of a single strand of RNA with negative polarity. The genus Ebolavirus includes five taxonomically named species: Bundibugyo ebolavirus (Bundibugyo virus), Reston ebolavirus (Reston virus), Sudan ebolavirus (Sudan virus), Taï Forest ebolavirus (Taï Forest virus), and Zaire ebolavirus (Ebola virus).Only Bundibugyo, Sudan, and Ebola viruses were associated with disease outbreaks in humans.
Since ebola viruses were first identified in 1976, over 20 known outbreaks of Ebola disease have been identified in sub-Saharan Africa, mostly in Sudan, Uganda, Democratic Republic of Congo and Gabon, mainly due to the Ebola and Sudan viruses. The largest outbreak to date from the Ebola virus occurred in western Africa from 2013 to 2016, affecting primarily Guinea, Sierra Leone and Liberia. It affected several countries, both rural and urban, with high incidence and mortality (> 28,000 cases with > 11,000 deaths).
Without specific treatment, the management of patients with Ebola virus disease consists of providing supportive and, where appropriate and wherever feasible, critical care on the basis of the pathophysiological similarities.
To date, no therapeutic therapy has been scientifically proven to specifically treat Ebola virus infections (i.e., effective in decreasing mortality). Promising research therapy data exist for small molecules with direct antiviral activity and candidate monoclonal antibodies (mAbs), some of which act by preventing the binding of Ebola virus glycoprotein (EboGP) to its cellular receptor.
Middle East Respiratory Syndrome
The Middle East respiratory coronavirus syndrome (MERS-CoV) is a lethal zoonotic pathogen first identified in 2012 in humans in Saudi Arabia and Jordan. Unfolding intermittent sporadic cases, community clusters and MERS-CoV nosocomial outbreaks persist. Between April 2012 and December 2019, 2,499 laboratory-confirmed cases of MERS-CoV infection were reported to the WHO from 27 countries, including 858 deaths (34.3% mortality), most of which Saudi Arabia reported (2,106 cases, 780 deaths). Significant outbreaks of human-to-human transmission have occurred, the largest in 2014 in Riyadh and Jeddah, and in South Korea in 2015. MERS-CoV remains a high-threat pathogen identified as a priority disease by the WHO because it causes severe disease with high mortality rates, epidemic potential and no medical countermeasure.
MERS-CoV is a large single-strand positive-sense RNA virus. The 30-31 kb coronavirus genome encodes a large number of proteins that could provide flexibility in adapting to new environments and enhancing transmission of cross-species. MERS-CoV has four structural proteins: the protein spike (S); the protein envelope (E); the protein membrane (M); and the protein nucleocapsid (N). The S protein is a type I transmembrane glycoprotein that is located on the virus surface as a trimmer and is composed of subunits S1 and S2. This has essential functions to bind, fuse and enter host cells. The subunit S1 has a receptor binding domain that binds dipeptidyl peptidase 4 (DPP4) to the host cellular receptor. The S2 subunit has two parts, the heptad repeats 1 and 2 (HR1 and HR2), which are rearranged to form a bundle of six helixes to allow for membrane fusion. The proteins E and M are present in the viral membranes and are essential for viral assembly, budding and intracellular traffic.
The WHO defines a primary MERS-CoV infection as a laboratory-confirmed MERS-CoV infection that has no clear epidemiological link to a human MERS-CoV infection and presumably was acquired outside a healthcare facility through direct or indirect contact with the host reservoir (dromedary camels). The WHO defines a secondary MERS-CoV infection as a laboratory-confirmed MERS-CoV infection with a direct epidemiological link to an individual with confirmed or probable MERS-CoV infection.
Treatment and Management
Currently, there are no specific anti-MERS-CoV therapies available for human use. Clinical management of MERS patients mainly focuses on symptoms, offers supportive care with management of pain and fever, manages primary or secondary bacterial infections and maintains essential organ functions.
Mild MERS cases can be managed at home. Predictive factors for pneumonia include patients older than 56 years, patients with high fever, thrombocytopenia, lymphopenia, C-reactive protein greater than or equal to 2 mg/dL, and high viral sputum load (threshold cycle value of rRT-PCR < 28.5). Respiratory failure and acute kidney injury (with hematuria and proteinuria) are common outcomes.
Look for our next article to further explore and dissect the history of global pandemics. To read the full BCC Research report please click here.
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