PROCESSES, PATHWAYS, CAUSES AND EFFECTS, AND MECHANISMS

Prolonged illness, disability, and death

What are the consequences of new resistance mechanisms emerging and spreading globally, threatening the ability to treat common infectious diseases?

Deliver high-quality, evidence-based, people-centered services

What is one of the five strategic directions of the Global Health Sector Strategies (GHSS) guiding priority actions for countries and WHO?

Optimize systems, sectors and partnerships for impact

What is one of the five strategic directions of the Global Health Sector Strategies (GHSS) guiding priority actions for countries and WHO?

Generate and use data to drive decisions for action

What is one of the five strategic directions of the Global Health Sector Strategies (GHSS) guiding priority actions for countries and WHO?

Engage empowered communities and civil society

What is one of the five strategic directions of the Global Health Sector Strategies (GHSS) guiding priority actions for countries and WHO?

Foster innovations for impact

What is one of the five strategic directions of the Global Health Sector Strategies (GHSS) guiding priority actions for countries and WHO?

Reduction of incidents with HIV per 1000 uninfected population to 0.05 by 2025, and to 0.025 by 2030

What are the disease-specific goals promoted by the GHSS to end AIDS epidemics by 2030?

90% reduction in the number of TB deaths

What is the 2030 target for the reduction of TB deaths in comparison to 2015 levels under the End TB Strategy?

80% reduction in the TB incidence

What is the 2030 target for the reduction of TB incidence in comparison to 2015 levels under the End TB Strategy?

35% reduction in the number of TB deaths

What is the 2020 milestone for the reduction of TB deaths under the End TB Strategy?

20% reduction in the TB incidence rate

What is the 2020 milestone for the reduction of TB incidence rate under the End TB Strategy?

Reducing malaria case incidence by at least 90% by 2030

What is a global target of the WHO Global technical strategy for malaria 2016-2030?

Reducing malaria mortality rates by at least 90% by 2030

What is a global target of the WHO Global technical strategy for malaria 2016-2030?

Eliminating malaria in at least 35 countries by 2030

What is a global target of the WHO Global technical strategy for malaria 2016-2030?

Preventing a resurgence of malaria in all countries that are malaria-free

What is a global target of the WHO Global technical strategy for malaria 2016-2030?

Diseases recognized in humans for the first time

What defines the category of Newly emerging infectious diseases?

Diseases that have historically infected humans but continue to reappear either in new locations or in resistant forms

What defines the category of Re-emerging infectious diseases?

Diseases associated with intent to harm

What defines the category of Deliberately emerging infectious diseases, such as agents for mass bioterrorism?

Diseases created by humans that are released unintentionally

What defines the category of Accidentally emerging infectious diseases, such as epizootic vaccinia?

Deforestation, damming or other changes in water ecosystems, flood or drought, famine

What are some examples of environmental changes that contribute to the emergence of infectious diseases?

Sexual behavior, drug use, outdoor recreation

What are some examples of changes in human behavior that contribute to the emergence of infectious diseases?

War, poverty, population growth and migration, urban decay

What are some examples of socioeconomic and demographic phenomena that contribute to the emergence of infectious diseases?

Highways, international air travel

What are some examples of travel and commerce factors that contribute to the emergence of infectious diseases?

Globalization of food supplies, changes in methods of food processing and packaging

What are some examples of food production changes that contribute to the emergence of infectious diseases?

New medical devices, blood transfusions, organ and tissue transplantation, drugs causing immunosuppression, widespread use of antibiotics, comorbid conditions

What are some examples of health care factors that contribute to the emergence of infectious diseases?

New viral strains arising through mutation, recombination or reassortment resulting in changes in transmissibility, virulence, or development of drug resistance

What defines the factor of microbial adaptation contributing to disease emergence?

Inadequate sanitation and vector control measures, curtailment of prevention programs, lack of trained personnel in sufficient numbers

What are some examples of inadequate public health measures that contribute to the emergence of infectious diseases?

Urbanization and other conditions that favor the rodent host; nosocomial transmission

What contributed to the emergence of Lassa Fever?

Unknown natural reservoir; nosocomial transmission

What contributed to the emergence of Ebola hemorrhagic fever?

Cooling and plumbing systems

What contributed to the emergence of Legionnaire disease?

Mass food production systems

What contributed to the emergence of Hemolytic Uremic Syndrome from E. coli O157:H7?

Conditions favoring the tick vector and deer, such as reforestation near homes

What contributed to the emergence of Lyme borreliosis?

Migration to cities, global travel, transfusions, organ transplants, intravenous drug use, multiple sexual partners

What contributed to the emergence of AIDS (HIV)?

Newly recognized as due to infectious agent

What contributed to the emergence of Gastric ulcers from Helicobacter pylori?

Evolution of new strain of bacteria combining increased virulence and long-term survival in the environment

What contributed to the emergence of Cholera from Vibrio cholerae O139?

Environmental changes favoring contact with rodent hosts

What contributed to the emergence of Hantavirus Pulmonary Syndrome?

Pig-duck agriculture (possibly)

What is a suggested contributing factor to the emergence of Pandemic influenza strains?

Can be easily disseminated or transmitted from person to person

What is a characteristic of high-priority Category A bioterrorism agents regarding transmissibility?

Result in high mortality rates and have the potential for major public health impact

What is a characteristic of Category A bioterrorism agents regarding fatality and public health impact?

Might cause public panic and social disruption

What is a social characteristic of Category A bioterrorism agents?

Require special action for public health preparedness

What is a requirement for public health systems regarding Category A bioterrorism agents?

Are moderately easy to disseminate

What is a characteristic of second-highest priority Category B bioterrorism agents regarding dissemination?

Result in moderate morbidity rates and low mortality rates

What is a characteristic of Category B bioterrorism agents regarding morbidity and mortality?

Require specific enhancements of CDC’s diagnostic capacity and enhanced disease surveillance

What is a requirement for public health systems regarding Category B bioterrorism agents?

Availability

What is a factor why Category C bioterrorism agents could be engineered for mass dissemination?

Ease of production and dissemination

What is a factor why Category C bioterrorism agents could be engineered for mass dissemination?

Potential for high morbidity and mortality rates and major health impact

What is a potential impact of Category C bioterrorism agents?

Caused polyclonal T-cell proliferation and release large amounts of IL-1 and TNF

What is the mechanism by which S. aureus superantigens drive disease pathology?

Forms membrane pores that allow calcium to enter cell

What is the mechanism of action of the S. aureus alpha-toxin that causes cell death and damage?

Serine proteases cleave desmoglein 1

What is the mechanism by which S. aureus Exfoliative A and B Toxins cause keratinocyte detachment and skin exfoliation?

Superantigens cause polyclonal T cell proliferation and release large amounts of IL-1 and TNF

What is the mechanism by which S. aureus causes the symptoms of Toxic Shock Syndrome?

Antistreptococcal M protein antibodies and T cells cross-react with cardiac proteins

What causes the cardiac manifestations of rheumatic fever?

Prevents the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) release

What is the mechanism of action of C. tetani toxins that causes spastic paralysis (tetanus)?

Neurotoxin binds gangliosides on motor neurons, and a fragment cleaves synaptobrevin

What is the mechanism of action of C. botulinum toxin that blocks acetylcholine release and causes flaccid paralysis?

Act A surface protein induces actin polymerization to propel the bacteria into adjacent uninfected cells

What mechanism allows Listeria monocytogenes to spread from cell to cell inside the host?

Phagosome manipulation inhibits maturation of phagosome and blocks formation of phagolysosome

What is the mechanism used by M. tuberculosis to survive and proliferate inside macrophages?

B subunit binds endothelial receptor, allowing delivery of A subunit into the host cell

What is the mechanism by which the Anthrax Toxin enters host cells?

Edema Factor (EF) binds calcium and calmodulin to form an adenylate cyclase, converting ATP to cAMP

What is the mechanism by which Anthrax Edema Factor alters host cell function?

Lethal Factor (LF) is a protease that destroys mitogen-activated protein kinase kinases

What is the mechanism by which Anthrax Lethal Factor causes cell death (though not fully understood)?

Capsule inhibits opsonization

What is the mechanism Neisseria meningitidis uses to avoid the immune system?

Binding to CD46 epithelial cell receptor via long pili

What is the primary adherence mechanism of N. gonorrhoeae to host epithelial cells?

Recombination of genes coding for pili proteins or expression of different OPA proteins

What mechanism allows N. gonorrhoeae to use antigenic variation to escape the immune response?

ADP-ribosylates and inactivates guanine nucleotide-binding proteins

What is the mechanism of action of the A unit of Pertussis Toxin?

Converts ATP to cAMP, which inhibits phagocytosis and oxidative burst in neutrophils and causes apoptosis of macrophages

What is the mechanism of action of the Bordetella pertussis Toxic Adenylate Cyclase?

Inhibits host protein synthesis via ADP ribosylation of Elongation Factor-2

What is the mechanism of action of P. aeruginosa A-B Exotoxin?

Injects bacterial proteins (Yops) into the host cell

What is the function of the Yop virulon plasmid-borne gene complex in Yersinia pestis pathogenesis?

Yops (YopE, YopH, YopT) block phagocytosis by inactivating actin polymerization

What is the mechanism by which Y. pestis blocks phagocytosis?

TprK protein gene undergoes recombination

What is the mechanism T. pallidum uses to cause antigenic diversity and escape the immune response?

Phospholipase C degrades cell membranes

What is the mechanism of action of Clostridium perfringens alpha-toxin, which leads to tissue damage?

Degrade extracellular matrix proteins

What is the function of Clostridium's collagenase and hyaluronidase enzymes in facilitating invasion and destruction?

Enterotoxin forms pores in epithelial cell membranes

What is the mechanism by which C. perfringens causes damage and diarrhea in food poisoning?

Neurotoxin cleaves synaptobrevin, blocking acetylcholine release

What is the ultimate mechanism of C. botulinum neurotoxin leading to flaccid paralysis?

Toxin A stimulates chemokine production, recruiting white blood cells

What is the mechanism of C. difficile Toxin A in pseudomembranous colitis?

Toxin B has direct cytopathic effects

What is the mechanism of C. difficile Toxin B in pseudomembranous colitis?

Urease dissociates urea into carbon dioxide and ammonia

What is the mechanism by which K. pneumoniae contributes to staghorn calculi formation?

Binding of bacterial lipoproteins to TLR2 on macrophages releases IL-6 and TNF

What is the mechanism that initiates immune damage in Lyme disease pathogenesis?

Bactericidal nitric oxide derivatives are generated

What is the effect of TNF and IFN-gamma release in the response against Rickettsia?

Bacteria enter cells by endocytosis but escapes from the endosome into cytoplasm using hemolysins

What is the mechanism Rickettsia uses to disrupt phagosomal membranes?

Elementary body prevents phagolysosome fusion

What is the mechanism C. trachomatis uses to survive inside the host cell after entry?

Adhesins bind to fibrinogen, fibronectin, laminin, epithelial cells, and endothelial cells

What is the role of Candida adhesins in infection?

Aspartyl proteinases degrade extracellular matrix proteins

What is the mechanism by which Candida proteinases contribute to invasiveness?

Catalases resist oxidative killing by phagocytic cells

What is the mechanism Candida uses to survive host defenses?

Beta-1,3-glucan engages dectin on dendritic cells, inducing IL-6 and IL-23 production

What is the mechanism for Candida activation of dendritic cells leading to TH17 response?

Glucuronoxylomannan polysaccharide capsule inhibits phagocytosis by alveolar macrophages and leukocyte migration

What is the mechanism Cryptococcus uses to evade host defenses and inflammation?

Laccase enzyme catalyzes the formation of melanin

What is the process that leads to melanin production in Cryptococcus?

Melanin production decreases antibody-mediated phagocytosis and has antioxidant properties

What are the mechanisms by which Cryptococcus melanin production contributes to virulence?

Phospholipases degrade cell wall components and aid in tissue invasion

What is the mechanism by which Cryptococcus phospholipases contribute to pathogenesis?

Urease helps neutralize the reactive oxygen species and pH of the phagocytic cell

What is the mechanism by which Cryptococcus urease contributes to survival inside phagocytes?

TLR2 recognizes Aspergillus conidia and lectin dectin-1 recognizes beta-1,3-glucan in swollen conidia

What mechanisms allow alveolar macrophages to recognize Aspergillus conidia?

Conidia germinate into hyphae and easily invade tissues

What happens in immunosuppressed patients that allows Aspergillus to cause invasive disease?

Airborne asexual spores are inhaled

What is the transmission route for Mucormycotina?

Macrophages provide initial defense via phagocytosis and non-oxidative killing of germination sporangiospores

What is the initial host defense mechanism against Mucormycotina?

TLR2 recognizes hyphal components, resulting in a pro-inflammatory cytokine cascade, including increased IL-6 and TNF-alpha

What is the mechanism that initiates the immune response to Mucormycotina hyphae?

High availability of free iron leads to increased growth

What mechanism links conditions like diabetes and deferoxamine chelation to increased Mucormycotina infection probability?

Local tissue necrosis, invasion of the arterial walls, and penetration of the periorbital tissues and cranial vault

What are the effects of Mucormycosis invasion that lead to meningoencephalitis?

Inhibits DNA polymerase

What is the mechanism of action of Brincidofovir (CMX001 or Tembexa) for poxvirus treatment?

Potent inhibitor of an orthopoxvirus protein required for the formation of an infectious virus particle

What is the mechanism of action of Tecovirimat (TPOXX) for poxvirus treatment?

Elevation of the body temperature exceeding the normal daily variation and occurs in conjunction with an increase in the hypothalamic set point

What is the physiological definition of fever (pyrexia)?

Elicited by endogenous pyrogens (cytokines) or exogenous pyrogenic substances

What is the general cause of fever?

Acts on thermoregulatory neurons of the hypothalamus to raise the body’s temperature set-point

What is the mechanism by which Prostaglandin E2 (PGE2) induces fever?