Lecture 4: Virus Transmission and Epidemiology PDF

Lecture 4 VIRUS TRANSMISSION AND EPIDEMIOLOGY  Lecture Outline Portals of virus entry Dissemination within a host Portals of virus exit Patterns of infection Epidemiology Epidemiological studies  Virus Transmission. To remain success...

Lecture 4 VIRUS TRANSMISSION AND EPIDEMIOLOGY  Lecture Outline Portals of virus entry Dissemination within a host Portals of virus exit Patterns of infection Epidemiology Epidemiological studies  Virus Transmission. To remain successful, a virus must be able to be transmitted from an infected individual to an uninfected host. To initiate a successful infection: 1. Sufficient numbers of virions must enter the host One virion is theoretically enough… but there are mechanical, chemical, and microbiological barriers to infection at every site of the body, as well as the host immune system 2. The host must be accessible to (come into contact with) the virus 3. The cells must be susceptible to infection Must express the cell surface receptors to which the virus binds Determines the tropism of the virus: the specificity of a virus for a particular type of cell or tissue To be considered as permissive, the cells have to contain the receptor for infection and the proteins and molecules within the cell that are necessary for replication to occur  A fighting balance Viral pathogenesis is how a virus causes disease within a host VIRUS HOST The viruses that exist today have evolutionarily been selected for their traits that allow them to circumvent host factors and initiate infection, although the most successful viruses are not the most virulent: an extremely pathogenic virus will kill its host, thereby eliminating its reservoir and interrupting the chain of infection to another susceptible host  Virus Transmission Portals of Portals of Entry Exit Infection (and possible dissemination within host)  Portals of Virus Entry Several different portals of entry are used Eyes by different viruses to gain entry into a new host Most viruses interact with cells of an epithelium, the layers of cells that line the outside surfaces and inner cavities of the body Mucosal epithelium lines all the internal surfaces of the body Respiratory tract Gastrointestinal tract Genital tract Some portals of entry bypass the epithelium Penetration through the skin (e.g., needle injection) Organ transplants Blood transfusion Transplacentally (through the placenta)  Portals of Virus Entry: The Skin The skin possesses barriers to viral infection: Sebum (oil) produced by skin glands creates an acidic environment Outermost strata of epidermis is not alive and cannot support viral infection or replication Transmission through the skin: Small cuts or abrasions in the skin that allow access to the lower, dividing layers Primarily localized infections Penetration of the epidermis through insect bites (mosquitoes, ticks, mites) Subcutaneous tissue can be accessed through animal bites, needle punctures, improperly sterilized tattooing or piercing equipment Viruses can gain entry into bloodstream directly or through draining lymph (which empties into the bloodstream) → dissemination of the virus to other locations  Portals of Virus Entry: Respiratory Tract The respiratory tract is the most common portal of entry into the body by viruses Consists of mucosal epithelium Upper respiratory tract: nose, nasal passages, sinuses, pharynx, and larynx (voice box) Lower respiratory tract: trachea (windpipe), bronchi (singular: bronchus), and lungs Upper Lower  Ticks : heartland virus, powassan virus, Colorado tick fever Portals of Virus Entry: Respiratory Tract virus Through placenta tract, In the respiratory Cytomegalovirus, viruses must variolaavoid:virus, herpes simplex virus-1, (transplacental) being trapped inherpes mucus simplex virus-2, measles virus, rubella virus Eye* being eliminated Adenoviruses, by antibodies herpesor simplex virus-1, cytomegalovirus, macrophages enterovirus 70, Coxsackievirus A24, rubella virus, measles virus, vaccinia virus Transplants -Table 5.1 Common PortalsHepatitis solid organs of EntryBand thehepatitis virus, VirusesCthat Use virus, Them HIV, cytomegalovirus, West Nile virus, rabies virus, lymphocytic choriomeningitis Portal Selected Human virus, herpes Viruses simplex virus,that Use this varicella Portal zoster virus Respiratory tract* adenovirus, measles, mumps, rubella, enterovirus D68, - blood influenza A virus, HIV, hepatitis influenza B virus, B virus, hepatitis rhinovirus, C virus, humanrespiratory T- syncytial virus, virus-1 lymphotrophic varicellaand zoster virus, variola -2, dengue virus,SARS-CoV1 Ebolavirusand 2 *Gastrointestinal tract several viruses are able toNorwalk virus, gain entry rotavirus, through mucouspoliovirus, entericatenteroviruses, membranes these locations hepatitis A virus, hepatitis E virus, sapovirus Genital tract Human papillomaviruses, HIV, hepatitis B virus, hepatitis C virus, herpes simplex virus-2 Skin - direct contact Human papillomaviruses, herpes simplex virus-1, molluscum  Portals of Virus Entry: Gastrointestinal Tract The human gastrointestinal tract (digestive tract) is a hollow tube that stretches from the oral cavity (mouth) to the anus Gastrointestinal tract transmission: From mother to child in breast milk Free virions or within infected cells HIV, human cytomegalovirus, West Nile virus Fecal-oral route Virions present in the feces of an infected individual gain entry into the oral cavity of another individual Table 5.1 Common Portalsinofcountries Common Entry and the proper without Viruses that Use Them sanitation or water-treatment facilities Portal PolioSelected Human Viruses that Use this Portal Ingesting contaminated food or water Respiratory tract* Norwalk adenovirus, measles,causing virus (Norovirus), mumps, rubella, enterovirus D68, influenza "stomach A "Winter flu" or virus, influenza VomitingB virus, rhinovirus, respiratory Disease”. Common syncytial virus,onvaricella cruise ship. zoster virus, variola Gastrointestinal tract Norwalk virus, rotavirus, poliovirus, enteric enteroviruses, hepatitis A virus, hepatitis E virus, sapovirus  Portals of Virus Entry: Genital Tract The human genital tract Females: vagina, cervix, uterus, fallopian tubes, ovaries Males: penis, urethra, scrotum, testes, epididymis, vas deferens, ejaculatory ducts, seminal vesicles, and prostate gland Sexually transmitted diseases (STDs) are transmitted directly via the genital tract Examples: Human papillomavirus (HPV) Hepatitis B, C virus HIV HSV-2  syncytial virus, varicella zoster virus, variola Gastrointestinal tract PortalsNorwalkofvirus, Virus Entry:poliovirus, rotavirus, The Eye enteric enteroviruses, hepatitis A virus, hepatitis E virus, sapovirus Raretract Genital to have infection of the eye Human itself papillomaviruses, HIV, hepatitis B virus, hepatitis C without injury (such as a puncture virus, herpes simplex virus-2 wound) Skin Infection of the cornea occurs contact - direct Herpes simplex virusHuman papillomaviruses, infection of the herpes simplex virus-1, molluscum cornea is the most contagiosum common infectious - penetration cause ofInjection/cuts into dermis corneal blindness : hepatitis B virus, hepatitis C virus, HIV, in the UStissue or subcutaneous Ebolavirus Infection of the conjunctiva of the eye or Mosquito : dengue virus, West Nile virus, eastern equine eyelid causes conjunctivitis (“pink-eye”) Adenovirus common encephalitis virus, Chikungunya virus, yellow fever virus Ticks : heartland virus, powassan virus, Colorado tick fever virus Through placenta Cytomegalovirus, variola virus, herpes simplex virus-1, (transplacental) herpes simplex virus-2, measles virus, rubella virus Eye* Adenoviruses, herpes simplex virus-1, cytomegalovirus, enterovirus 70, Coxsackievirus A24, rubella virus, measles virus, vaccinia virus Transplants  Portals of Virus Entry: The Placenta The placenta is a fetal tissue that facilitates the transfer of oxygen, carbon dioxide, waste products, and nutrients between the mother and fetus Fetal and maternal blood does not mix, but close contact allows diffusion to occur Congenital infections: viruses present at the time of birth, transmitted transplacentally or during birth from the birth canal Cause severe effects, including miscarriage, low birth weight, intellectual deficiencies, hearing loss, and death Henry Gray, Anatomy of the Human Body. Philadelphia and New York, Lea and Febinger, 1918. Portal Selected Human Viruses that Use this Portal Respiratory tract* Portals of Virusmeasles, adenovirus, Entry: The Placenta mumps, rubella, enterovirus D68, influenza A infection Vertical transmission: virus, influenza fromB virus, mother rhinovirus, to childrespiratory syncytial virus, varicella zoster virus, variola Gastrointestinal tract Norwalk virus, rotavirus, poliovirus, enteric enteroviruses, hepatitis A virus, hepatitis E virus, sapovirus Genital tract Human papillomaviruses, HIV, hepatitis B virus, hepatitis C virus, herpes simplex virus-2 Human cytomegalovirus Skin is the most common - direct contact Human papillomaviruses, herpes causesimplex virus-1, molluscum of congenital contagiosum infections, occurring in - penetration into dermis Injection/cuts : hepatitis B virus, hepatitis C virus, HIV, 2.5% of live births or subcutaneous tissue Ebolavirus Mosquito : dengue virus, West Nile virus, eastern equine encephalitis virus, Chikungunya virus, yellow fever virus Ticks : heartland virus, powassan virus, Colorado tick fever Table 5.1 Common Portals of Entry and the Viruses that Use Them virus Through placenta Cytomegalovirus, variola virus, herpes simplex virus-1, Portal (transplacental) Selected Human herpes simplex Viruses virus-2, that Use measles this virus, Portal rubella virus HIV Respiratory Eye* tract* adenovirus, Adenoviruses,measles, herpesmumps, simplexrubella, virus-1, enterovirus D68, cytomegalovirus,  Portals of Virus Entry: Transplants (blood) Viruses can be transmitted through transplanted organs and tissues Blood is the most common transplanted tissues Transfusion-transmitted infections (TTIs) Blood supply is screened for many high-impact viruses New viruses can contaminate donated blood before tests exist to detect them 20,000 people contracted HIV from the blood supply before 1985 More than half of all the hemophiliacs in the US Table 5.2 Pathogens for which the blood supply is currently tested Pathogen Type Specific Pathogens Tested For Virus Hepatitis B virus (HBV) Hepatitis C virus (HCV) Human immunodeficiency virus -1 and -2 (HIV-1/HIV-2) Human T-lymphotropic virus -1 and -2 (HTLV-1/HTLV-2) West Nile Virus Bacterium Treponema pallidum (syphilis) - direct contact Portals of Human Viruspapillomaviruses, Entry: Transplantsherpes simplex virus-1, molluscum (organs) contagiosum Organ transplants - penetration into dermiscanInjection/cuts also harbor virusesB (although : hepatitis transmission virus, hepatitis C virus, HIV, or subcutaneous through solid tissue organs isEbolavirus rare) Mosquito : dengue virus, West Nile virus, eastern equine Organ recipients encephalitis are given virus, Chikungunya potent drugs to virus, yellow fever suppress thevirus immune Ticks : heartland virus, powassan virus, Colorado tick fever system, leading to an immunocompromised individual virus Through placenta Cytomegalovirus, variola virus, herpes simplex virus-1, (transplacental) herpes simplex virus-2, measles virus, rubella virus Eye* Adenoviruses, herpes simplex virus-1, cytomegalovirus, Table 5.1 Common Portals enterovirus of Entry70, andCoxsackievirus A24, Use the Viruses that rubella virus, measles Them virus, vaccinia virus Transplants Selected Human Viruses that Use this Portal Portal - solid organs Hepatitis B virus, hepatitis C virus, HIV, cytomegalovirus, Respiratory tract* adenovirus, measles, mumps, rubella, enterovirus D68, West Nile virus, rabies virus, lymphocytic choriomeningitis influenza A virus, influenza B virus, rhinovirus, respiratory virus, herpes simplex virus, varicella zoster virus syncytial virus, varicella zoster virus, variola Gastrointestinal - blood tract Norwalk virus, rotavirus, poliovirus, enteric enteroviruses, HIV, hepatitis B virus, hepatitis C virus, human T- hepatitis A virus, lymphotrophic hepatitis virus-1 and -2,Edengue virus, sapovirus virus, Ebolavirus Genital tract Human papillomaviruses, HIV, hepatitis B virus, hepatitis C  Dissemination within a Host Localized infections infect and replicate only within cells at the initial site of infection Systemic infections initiate infection in one organ and spread to other sites within the body Neurotropic spread: spread through neurons Virus replicates in local tissue and then infects neurons Peripheral nerves can be used to access the central nervous system herpesviruses (HSV-1, HSV-2, varicella zoster virus), polio, rabies Hematogenous spread: spread through the bloodstream Viremia: virus in the bloodstream Primary viremia: first time the virus is in the blood Secondary viremia: virus in the blood following replication in an organ that was infected through the primary viremia Can occur directly (through injection or animal bites) or indirectly from high amounts of replicated virus spilling over from the local infection site  Portals of Virus Exit Shedding is the release of infectious virions from an infected individual During localized infection, virions are shed from the site of infection Skin-to-skin contact (for skin-infecting viruses) Respiratory secretions (for respiratory viruses) Diarrhea or aerosolized vomit (for gastrointestinal viruses) Saliva (for viruses that replicate within salivary glands or oral compartments) Genital secretions (for STDs) Systemic infections may be spread through local sites or from: Blood / bodily fluids Viruria: virus within the urine Feces  Portals of Virus Exit The stability of virions within the environment depends upon several factors, both of the environment and of the virion itself Table 5.3 Characteristics that affect virion stability Factor Characteristic Virion Type of nucleic acid (DNA more stable than RNA) Sensitivity of viral proteins to pH changes Presence/absence of envelope (envelope is susceptible to detergents) Sensitivity to damage from ultraviolet light Strain of virus Adsorption to other materials Particle size Aggregation of virions Environment Temperature pH Humidity Seawater/freshwater/distilled water Amount and type of organic matter Presence of other organisms Salinity Presence of enzymes or degrading factors Type of surface / medium  Portals of Virus Exit Airborne viruses are transmitted via the respiratory route when a person coughs, sneezes, speaks, or breathes Droplets, ~20 microns in size, are only spread short distances before they succumb to gravity and fall out of the air (especially at higher humidity) Aerosolized particles, ~5 microns in size, remain airborne for longer greater success in reaching the lower respiratory tract  Periods of Infection An infected host typically goes through 4 stages of disease development  Patterns of Infection Patterns of Disease: Acute infection Rapid replication of the virus within the host Spread of virus to others Immune system clears the infection within 1-2 weeks Can be inapparent/subclinical; but can still spread to others can still occur! Most viral infections fall into this category, e.g., flu. COVID Persistent infection Host immune system is unable to clear the infection Infection does not kill the host Infection can be lifelong E.g., hepatitis B. Latent infections. The infected virus become dormant and patients shows no symptom Reactivation may occur E.g., HIV, HSV  Epidemiology Epidemiology = the study of how disease spreads throughout a population Epidemiologists determine how a disease is transmitted from person to person and establish control measures that interrupt the continued transmission of the virus  Epidemiology: Disease Occurrence Terminology Sporadic: infrequently, without a consistent pattern Endemic: the usual presence of a disease in a population or an area at any given time Epidemic: more cases of a disease (a sudden increase) in a particular area than are expected during endemic times Also referred to as an “outbreak” Pandemic: when an epidemic spreads through several countries, a continent, or the world  Epidemiology: Disease Occurrence Terminology Sporadic, Endemic, Epidemic, or Pandemic? 1. 20 million people worldwide died of influenza in 1918-1919. 2. 60 cases of yellow fever virus are usually reported in this region per week of the year. 3. 122 cases of norovirus were reported last week in Chicago (normal is 1-5 cases each week). 4. A single case of the rare lymphocytic choriomeningitis virus was reported in Rhode Island this week.  Epidemiology: Chain of Infection The details of the epidemiologic triad model can be further examined by inspecting the factors found within the chain of infection: Transmission of the agent to the host occurs when the agent leaves its reservoir through a portal of exit, is conveyed by a mode of transmission, and enters a susceptible host through a portal of entry.  Epidemiology: Chain of Infection Humans are the most common reservoirs of human viruses Some exclusively within humans Poliovirus or variola virus (cause of smallpox) Others infect humans and other animals Zoonosis: infectious disease that can be transmitted from an animal to a human Influenza A virus, Ebola virus, MERS-CoV, SARS-CoV-1, SARS-CoV- 2 A carrier is a reservoir that can transmit the pathogen but shows no symptoms of infection  Epidemiology: Control measures Control measures interfere with the transmission of the virus Can be instituted at any point within the chain of infection Most often directed at controlling/eliminating the virus at its source, preventing the transmission of the virus, protecting portals of entry, and increasing host defenses Examples: Prevent virus from leaving infected individual (antivirals) Remove/relocated infected animal hosts Isolate infected individuals (quarantine) Rearrange environment Ventilation systems Water treatment Insect-spraying programs Protect portals of entry Personal protective equipment (PPE) Handwashing Sterilization measures Bed nets Long pants  Epidemiology: Control measures The most effective control measure that protects the susceptibility of the individual is vaccination. Works by exposing an individual to non-infectious parts of a pathogen to prepare the immune system for the actual pathogen Protects the individual Protects a population through herd immunity  Epidemiology: Herd immunity and infection control Herd Immunity Transmission of a pathogen within a population is prevented due to lack of susceptible hosts because of vaccination R0 and the percentage of the population needs to be vaccinated