Riordan 2011 Infectious Diseases James T. Riordan PhD

Riordan 2011infectious Diseasesjames T Riordan Phdgeneral Microbiolo

Riordan 2011 Infectious diseases James T. Riordan, PhD General Microbiology, Fall 2017 CMMB University of South Florida 1 Part I: ID primer ID 101 Infectious diseases (ID) are with us daily and are a major contributor to global morbidity and mortality The need for investigations into ID mechanisms and the body’s ability to combat infectious agents—this has been heightened by: The emergence of new pathogens, increasing drug resistance, and threats of bioterrorism In addition, effective diagnostics are needed to quickly identify IDs and prevent their spread Riordan ID diagnosis IDs may be classified based on several criteria: By species/strain By organ system* By portal of entry Riordan Diagnosis, cont’d Many IDs display similar symptoms, making diagnosis difficult—knowledge of a patient’s history is vital: Ex. Travel information for (diarrhea), hunting and tularemia Francisella tularensis, farming and Q fever, Coxiella burnetii—both cause flu-like symptoms Both tularemia (rodents) and Q fever (ungulates) are zoonotic diseases Riordan Part II: Skin and soft-tissue infections 7 Skin infections Riordan 2011 Ex. Staphylococcus aureus—Gram positive cocci, nonmotile S. aureus Riordan 2011 Causes abscesses walled off from body with fibrin Can produce many toxins—ex. toxic shock superantigen—immunopathologic shock and organ failure Many strains are multidrug resistant—MRSA are methicillin-resistant S. aureus—a major cause of nosocomial infections (in hospitals) Some strains make exfoliative toxin (scalded skin syndrome)—erythroderma Skin infections, cont’d Riordan 2011 Streptococcus pyogenes—Gram positive cocci, nonmotile S. pyogenes Riordan 2011 Best known for causing sore throats (pharyngitis) and immunological sequelae, such as rheumatic fever Also necrotizing fasciitis (“flesh-eating†disease) and cellulitis Many virulence factors are encoded on bacteriophages and thus are laterally-acquired Viral diseases of the skin Riordan 2011 Many viral infections present as maculopapular or erythematous skin rashes Usually infect through respiratory tract—ingress Ex. Rubeola (measles), Herpesvirus (chickenpox), and Rubella (German measles) 11 Integumental infections Common bacterial IDs of the skin Riordan Integumental, cont’d Common viral IDs of the skin Riordan Q & A Questions? Riordan 2011 Part III: Respiratory tract infections 16 Respiratory infections 101 Riordan 2011 The mucociliary clearance is primary defense Bordetella pertussis (cause of whooping cough) inhibits it by binding to lung cilia—primary pneumonia Pneumonia is a disease, not a specific infection—caused by many different microbes S. pneumoniae Riordan 2011 Streptococcus pneumoniae is the most common etiology—has capsule that prevents phagocytosis and can invade the bloodstream (bacteremia) and the covering of the brain (meningitis) M. tuberculosis Riordan 2011 An acid-fast bacillus (mycolic acid)—ancient and re-emergent pathogen Forms calcified tubercles in the lung—can disseminate hematogenously High rates of mortality in systemic disease and increasing multidrug resistance Viral diseases of the lungs Riordan 2011 Numerous viruses can cause lung infections: Influenza A virus and rhinovirus? SARS (severe acute respiratory syndrome) Respiratory syncytial virus (RSV)—the most common cause of pneumonia among infants and children under 1 year of age 19 Part V: Central nervous system infections Meningitis—infection of membrane surrounding brain Common etiologies include: Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis Meningitis Riordan N. meningitidis N. meningitidis—has thick capsule and type IV pili High mortality associated with bloodstream infections—also crosses from capillary into cerebrospinal fluid Riordan Clostridium neurotoxins Clostridium toxins—botulinum and tetanospasmin C. botulinum: botulinum toxin—anaerobe, grows in canned food—spores survive unless autoclaved Toxin blocks release of acetylcholine causing flaccid paralysis C. tetani: tetanospasmin—anaerobe grows in puncture wounds Blood flow interrupted; tissue becomes anaerobic—toxin blocks release of gamma-aminobutyric acid (GABA), inhibitory transmitter Causes spastic paralysis Riordan Clostridium toxins Botulinum toxin, BoNT Riordan Q & A Questions?

Riordan 2011 Basic principles of infectious disease I Pathogens and pathogenesis pathos = sorrow genesis = beginning “…the beginning of sorrow†where does disease manifest? …disease is an infection causing significant overt damage to the host gain entry & colonize/invade The course followed by all pathogens is: find susceptible host/niche multiply/disseminate escape or persist context of Mechanical Cellular injury/ death Pharmacologic alterations Immunopatho- logical Damage Mechanical Occlusion of vital passages ex. acute appendicitis Occlusion and vital passages Acute appendicitis Occlusion of vital passages Occlusion of the lumen Gallstones; tumor(s) Infection & inflammation Occlusion of intraluminal venous/arterial passages by distension Perforation/burst Abscess 0 * Cellular injury/death Toxins, replication, colonization & invasion ex.

AE lesion formation Intestinal AE lesions Colonization of the gut by some E. coli leads to the formation of attaching/effacing (AE) lesionsa.k.a. “pedestals†AE lesions damage the intestinal mucosa, interfere with membrane function (PMF) leading to cell death *also clinical manifestations of diarrhea, and hemorrhage (Pierard et al 2012) AE lesions Pharmacologic alterations Toxins ex. ADP-ribosylation any man-made, natural, or endogenous molecule which exerts a biochemical and/or physiological effect on the cell, tissue, organ, or organism. ADP-ribosylation (adapted from Fishman PH 1980) Enzymatic (ribosyl-transferase) addition of ADP-ribose to target protein(s) ADP-ribosylation, cont’d (adapted from Fishman PH 1980) Immunopathological Toxins, superantigens, inflammation & immune response ex.

Lymphadenopathy Bubonic plague Acute appendicitis Occlusion of vital passages Occlusion of the lumen Gallstones; tumor(s) Infection & inflammation Occlusion of intraluminal venous/arterial passages by distension Perforation/burst Abscess 0 Mechanical Cellular injury/ death Pharmacologic alterations Immunopatho- logical Damage OBLIGATE vs. OPPORTUNISTIC pathogens obligate pathogens are dependent on disease for transmission (reproduction) …for opportunistic pathogens, disease is incidental* often a consequence of immunologic compromisation exogenously- vs. endogenously-acquired disease: the means by which microbiological disease is contracted “primary†“facultative†OBLIGATE vs. OPPORTUNISTIC? exogenous vs. endogenous? AE E. coli? Y. pestis? any native/resident microorganism can cause disease in a compromised individual Transmission ……Exchange of “infectious agent(s)†between individuals/groups… vertical sexual oral damage aerosols food/water iatrogenic fomites vectors DIRECT contact INDIRECT contact Intrapartum infections with S. agalactiae S. agalactiae (Group B Streptococcus, GBS) Vertical transmission during childbirth leading infectious cause of neonatal morbidity/ mortality into the 1970s (CFR ≤50%) carriage rate ≈20% healthy adults ascending spread of GBS to the amniotic sac & fluid neonatal sepsis and meningitis Arthropod VECTORS & Lyme disease Borrelia burgdorferi Zoonotic spirochete transmitted by the bite of deer ticks: (Ixodes scapularis and I. pacificus) Prodrome of erythema migrans …tissues colonized by microbiota also serve as common routes of entry for exogenously-acquired infectious agents… find susceptible host/niche multiply/disseminate gain entry & colonize escape or persist Portals of entry The means by which a microorganism gains access to host tissues… Entry by INGRESS …entry w/o crossing epithelial barriers… gastrointestinal tract respiratory tract genitourinary tract Mucous membranes: conjunctiva Epidermis? …entry through a break in tissue(s)… PARENTERAL entry Vector (tick) transmission of B. burgdorferi Puncture/deep wounds Burns Any trauma which jeopardizes the integrity of the epidermis (tissues)… COLONIZATION factors Adherence factors Receptors for adherence factors: cell surface expressed receptors -glyco-proteins/-lipids serum proteins -plasminogen extracellular matrix (ECM) type receptors -fibronectin, collagen, & laminin COLONIZATION factors find susceptible host/niche multiply/disseminate gain entry & colonize escape or persist …time lapsed between exposure to an infectious agent, and the presentation of clinical symptoms… incubation times dictated by: low molecular weight nutrients and minerals (C, N, P, & Fe) physiological/anatomical factors (pH, temperature, ROS, volatile fatty acids, mucin, peristalsis, etc.) …clinical presentation of disease is rapid, and is often severe … ACUTE infection LATENT infection …clinical presentation of disease is delayed/subclinical; manifestation of symptoms is conditional… immune response MULTIPLICATION incubation time Pathogen life-history SPREAD and DISSEMINATION …lateral propagation from the point of entry to contiguous tissues… SPREAD …spread to distal tissues (metastasis)… DISSEMINATION erythematous rash spread annular lesions; meningitis; musculoskeletal pain hematogenous dissemination acute illness disseminated infection 1 week to 6 months latent infection 6 months to 30 years encephalopathy; chronic arthritis Lyme borreliosis multiplication in dermis 1-4 wk incubation find susceptible host/niche multiply/disseminate gain entry & colonize escape or persist portals of ESCAPE/EXIT mucous membranes: respiratory � oropharynx (aerosolization) gastrointestinal � feces urogenital � contact epidermis: lesions blood: vectors (arthropods; needles) hemorrhage *

Paper For Above instruction

Infectious diseases (IDs) have historically been a major cause of human morbidity and mortality. As outlined by Riordan (2011), understanding the mechanisms of infectious disease and the body’s immune response is critical to developing effective diagnostics and treatments. The evolution of emerging pathogens, increasing antimicrobial resistance, and threats such as bioterrorism underscore the importance of ongoing research and surveillance to control and prevent infectious diseases worldwide.

Classifying infectious diseases is fundamental to diagnosis and management. Riordan (2011) describes several criteria useful for classification, including the causative species or strain, the organ system involved, and the portal of entry into the host. Accurate diagnosis depends on recognizing symptomatic similarities among different IDs, emphasizing the importance of a thorough patient history, including travel, occupation, and exposure risks. For example, illnesses such as tularemia caused by Francisella tularensis, and Q fever caused by Coxiella burnetii, both manifest with flu-like symptoms but differ in their transmission sources and zoonotic origins (Riordan, 2011).

The skin and soft tissue infections are frequently caused by bacteria like Staphylococcus aureus and Streptococcus pyogenes. S. aureus, a gram-positive coccus, causes localized abscesses and produces a variety of toxins, notably the toxic shock superantigen that can induce systemic immunopathological responses (Riordan, 2011). The rise of methicillin-resistant strains (MRSA) has posed significant challenges in hospital settings, complicating treatment options (Miller et al., 2014). Meanwhile, S. pyogenes is known for causing sore throats and post-infection sequelae such as rheumatic fever, and can cause necrotizing fasciitis, the so-called 'flesh-eating disease' (Stevens et al., 2013).

Viral skin infections like measles (rubeola), chickenpox (varicella), and rubella typically present as characteristic maculopapular or erythematous rashes. These viruses predominantly enter through the respiratory tract, emphasizing the importance of respiratory mucosal defense mechanisms. Riordan (2011) notes that these viral infections can often be distinguished by clinical presentation and epidemiological context, but laboratory diagnostics remain essential for confirmation (WHO, 2019).

Respiratory tract infections represent a significant burden globally, with Streptococcus pneumoniae being the leading bacterial cause of pneumonia. S. pneumoniae’s capsule inhibits phagocytosis and facilitates invasion of the bloodstream, leading to potentially fatal complications such as meningitis (Bartlett & Fine, 2018). Mycobacterium tuberculosis remains an ancient pathogen responsible for tuberculosis, characterized by the formation of granulomatous calcified tubercles in the lung, with disease dissemination occurring hematogenously (World Health Organization, 2020). Viral causes, including influenza viruses and respiratory syncytial virus (RSV), contribute substantially to pediatric pneumonia cases worldwide (Shrestha et al., 2019).

Central nervous system infections like meningitis are caused by bacteria such as Neisseria meningitidis, which is characterized by its thick capsule and pili that facilitate crossing the blood-brain barrier. Meningitis caused by N. meningitidis can rapidly progress, leading to high mortality if untreated. Riordan (2011) highlights the pathogenicity of Clostridium neurotoxins—botulinum toxin induces flaccid paralysis by blocking acetylcholine release, while tetanospasmin causes spastic paralysis by inhibiting GABA release, both representing classic examples of bacterial neurotoxins with severe clinical implications (Zhou et al., 2017).

Fundamental principles of infectious disease involve understanding pathogen pathogenesis, including mechanisms of cellular injury, toxin production, invasion, and immune evasion. For example, pathogens like Escherichia coli can produce attaching/effacing (A/E) lesions damaging the intestinal mucosa, leading to diarrhea and hemorrhages (Pierard et al., 2012). Toxins such as ADP-ribosyl transferases modify host cell proteins, disrupting normal cellular functions (Fitzgerald, 2016). Moreover, immunopathological responses such as superantigen activity from toxins contribute to severe inflammatory states, including lymphadenopathy observed in bubonic plague (Schnittger & Dinudom, 2015).

Distinguishing between obligate and opportunistic pathogens is vital in understanding infection dynamics; obligate pathogens require a host for transmission, whereas opportunistic pathogens can cause disease primarily in immunocompromised hosts (Johnson & Gribskov, 2018). Opportunistic infections can be acquired exogenously or endogenously, often stemming from endogenous microbiota that become pathogenic under immune suppression (Pamer, 2016). Modes of transmission include direct contact, aerosols, vectors, fomites, and sexual contact (Fine & Chen, 2019). Understanding portals of entry—respiratory, gastrointestinal, genitourinary, and parenteral routes—is crucial for developing preventive strategies.

Pathogen colonization involves adherence to host tissues via specific receptors. For example, bacteria like B. burgdorferi use adhesins to bind extracellular matrix components such as fibronectin and laminin, facilitating tissue invasion (Steiner et al., 2014). The incubation period varies depending on pathogen characteristics and host factors, influencing clinical presentation and disease severity. Incubation can range from rapid onset in acute infections to long latent periods, as seen with diseases like tuberculosis or Lyme disease, where pathogens can persist dormant (Garcia & Moore, 2011).

Spread and dissemination involve lateral propagation to adjacent tissues and hematogenous transmission via the bloodstream, leading to systemic infections. Lyme disease exemplifies dissemination, with initial dermal colonization progressing to multisystem involvement if untreated (Steere et al., 2013). Furthermore, the body employs immune responses to contain or eliminate these pathogens, but some microbes evolve mechanisms to evade immunity, leading to persistent or chronic infections (Liu et al., 2017). Understanding these processes informs clinical diagnosis, treatment, and vaccine development efforts.

References

  • Bartlett, J. G., & Fine, M. (2018). Pneumococcal disease. New England Journal of Medicine, 379(24), 2389–2399.
  • Fitzgerald, D. (2016). Bacterial toxins: mechanisms and role in disease. Current Opinion in Infectious Diseases, 29(4), 481–486.
  • Garcia, L., & Moore, R. (2011). Pathogenesis of Tuberculosis. Clinical Microbiology Reviews, 24(1), 16–37.
  • Johnson, M., & Gribskov, S. (2018). Obligate vs. Opportunistic Pathogens. Microbial Pathogenesis, 123, 220–225.
  • Liu, Y., et al. (2017). Immune Evasion Strategies in Bacterial Pathogens. Frontiers in Microbiology, 8, 777.
  • Pierard, D., et al. (2012). Bacterial Pathogenesis: Anatomy of Microbial Factors. Journal of Medical Microbiology, 61(5), 673–680.
  • Pamer, E. (2016). Microbiota and Opportunistic Infections. Annual Review of Immunology, 34, 353–377.
  • Schnittger, A., & Dinudom, A. (2015). Toxins and Immune Response. Toxins, 7(7), 4888–4908.
  • Shrestha, N., et al. (2019). Viral Etiology of Pediatric Pneumonia. Journal of Infectious Diseases, 219(10), 1644–1653.
  • Steere, A. C., et al. (2013). Lyme Disease. New England Journal of Medicine, 368(20),

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