Infections

• Defence Mechanisms Against Infection

  • Physical and biochemical barriers – to prevent entry into body

  • Innate (natural) immunity – rapid, but non-specific response to

  any pathogen

  • Adaptive (acquired) immunity – delayed, but specific response

  to particular pathogen and improves on repeated contact, with

  memory

  • There is an interaction between all these systems
• Physical & Biochemical Barriers

  • Acts as the first line of defense

  • Examples include:

   pH: saliva, stomach, skin, vagina

   Flushing mechanisms: tears, urine flow, cilia

   Mucous production: traps organisms

   Secreted substances, e.g. lysozyme (tears, nasal & secretions) which damages the cell wall of Gram positive bacteria

   Peristalsis of the gut

   Skin: sweat, shedding upper layers

  • Disruption in any of these barriers allows organisms to bypass

  the first line of defense
• Indigenous Flora

  • Variety of organisms

  • Occupy ecological niches and help to maintain the environment and prevent infection with other organisms

  • They occupy epithelial surfaces and compete for essential nutrients

  • They secrete inhibitory substances ‘bactericidins’ that inhibit/ kill pathogens
• Innate Immunity

  • Acts as the second line of defense

  • Main cells involved:

   Phagocytes – neutrophils and macrophages

   Extracellular killers – NK cells and eosinophils

  • Soluble factors such as complement, and acute phase proteins are also involved

  • Disruption in any of these components allows organisms to bypass the second line of defense
• Neutrophils

  • Normally neutrophils migrate to the site of inflammation through chemotaxis

  • They phagocytose and kill bacteria with the assistance of macrophages

  • Infection is generally indicated by granulocytosis or neutrophilia in peripheral blood

  • These neutrophils are recruited from those marginal cells on the sides of blood vessels, and from the reserve in the bone marrow, augmented by increased production in the bone marrow
• Neutropaenia

  • Neutropaenia is defined as an absolute neutrophil count <1500 cells/microL (1.5 × 10ଽ cells/L) in an adult

  • Categorised as mild, moderate, severe (profound)

  • There is increased risk of infection, dissemination, severe sepsis and death
• Colonisation occurring on damaged mucosa would allow translocation from the alimentary tract or local infection
• Antimicrobial agents used for prophylaxis exert selective pressure on the ecology resulting in more resistant members of the resident flora increasing in number
• Resident flora

  • Viridans Streptococci
  • Staphylococci
  • Gram-negative bacilli
  • Yeasts
• Chemotherapy induces injury to the mucosal barrier
• Neutropenic patients are at risk of infections with multi-resistant organisms
• The gastric acid barrier of the stomach is usually breached by the use of drugs such as histamine type 2 antagonists and proton pump inhibitors
• Gastric acid barrier breached

  Microorganisms that are ingested pass onward to the small intestine and beyond
• Colonisation occurring on damaged mucosa

  Can lead to bloodstream invasion and ultimately to systemic infection
• Risks of infection may vary over time and course of treatment
• Causative organisms

  • Opportunistic
  • Primary pathogens
• Mucositis

  • Treatment such as radiation therapy or chemotherapy can cause damage to gut integrity anywhere along the length of the gut – this leads to ulceration and inflammation

  • Clinically there may be pain, swelling, difficulty eating and swallowing, diarrhoea and changes in mucous production

  • There is significant morbidity and many complications, especially infection

  • This provides a portal of entry for organisms in gut – gut translocation
• Adaptive Immunity

  • Acts as the third line of defense

  • Humoral immunity – B-cell mediated and involves soluble factors (antibodies) and works best for extra-cellular pathogens

  • Cellular immunity – T-cell mediated and works best for intracellular pathogens such as viruses and certain bacteria

  • There is an interaction between cellular and humoral immunity to form a coordinated immune response
• Infections in the Immunocompromised

  They are determined by:

  • Type of immune deficit

   Specific defects in the host immune system make the host susceptible to infections due to organisms normally cleared in that manner

   Immune system is very coordinated

   Patients can have multiple defects

  • Severity of immune deficit

   Primary vs secondary

  • Duration of immune deficit

   Acute vs chronic
• Immunocompromised hosts:

  Extremes of ages • Pregnant women • Patients undergoing long term cytotoxic therapy, immunosuppressive drugs, irradiation • Haematological malignancy • HIV/AIDS • Diabetes • Stem cell transplant patients
• • Virulence – the ability of a microorganism to cause disease in the host

  • Primary pathogen – organism that can cause disease in a host

  regardless of the host’s resident microbiota or immune system

  • Opportunistic pathogen – an organism that can only cause disease in situations that compromise the host’s defenses

  • Latent infection – an infection that does not produce signs of disease i.e. it is asymptomatic, but can be activated under certain circumstances

   Examples include:

  o Certain viruses, especially herpes viruses

  o Tuberculosis
• Opportunistic Pathogens

  • Pseudomonas aeruginosa

  • Mycobacteria

  • Aspergillus infections

  • Herpes viruses

  • Pneumocystis jirovecii
• Pseudomonas aeruginosa

  • Gram-negative bacteria

  • Rarely infects healthy tissues

  • Causes infection if normal host defenses are compromised and can infect virtually all tissues

  • Predominantly nosocomial infections (hospital) e.g. keratitis in contact lens wearers, skin and soft tissue infections, complicated intra-abdominal infection, ventilator acquired pneumonia

  • Infection can be severe, even life-threatening

  • Neutropaenia is a major risk factor for severe infection

  • Persistence in environment (especially in hospital environment)

  • Virulence factors

  • Antimicrobial resistance
• Mycobacteria

  • M. tuberculosis

   Newly acquired or re-activation of latent disease

   As immunity falls there is potential for disseminated TB and extra pulmonary disease

  • Non-tuberculous mycobacteria (NTM)

   M. avium/intracellulare
• Aspergillus Infections

  • Filamentous mould acquire from the environment via inhalation

  • Risk of infection, especially pneumonia

  • Flowers in wards are dangerous – fungal spores
• Herpes Viruses

  • Chronic or latent infections

  • Immunosuppression allows re-activation/ acquisition

   Herpes Simplex virus

   Varicella-Zoster virus

   Cytomegalovirus
• Pneumocystis jirovecii

  • Fungus

  • Both trophozoite and cystic forms

  • Transmission is airborne – exposure is common, likely in childhood

  • Causes diseases in HIV/AIDS and transplant patients (organ and stem cell) and acute leukaemia
• Organisms Causing Infection in Neutropenic Patients

  • Bacteria

   Gram-negative bacilli, including Pseudomonas aeruginosa

   Gram-positive cocci including viridans Streptococci

   Endogenous or exogenous – risk of hospital-acquired infection and risk of resistant organisms

  • Fungi

   Candida albicans and other Candida species

   Moulds or filamentous fungi e.g. Aspergillus fumigatus

  • Viruses

   Herpes simplex
• HIV/AIDS

  • Decrease in CD4 helper T cells

  • With lower CD4 counts more opportunistic pathogens can cause infection

  • Co-ordination of immune system is impaired

  • There is an increase in diseases normally controlled by T cell

  immunity

   Mycobacterium tuberculosis

   Cryptococcus neoformans

   Herpes viruses, including CMV

   Malignancies

  • B cell immunity is also impaired

   There may be an increase in severe pneumococcal infections (Streptococcus pneumoniae)
• Vascular insufficiency

  Local tissue ischaemia, promotes growth of anaerobic or micro-aerophilic organisms while depressing function of leucocytes and inflammatory response
• Diabetes Mellitus

  Hyperglycaemia – there is impairment of the immune response, particularly of neutrophils
• Sensory peripheral neuropathy

  Unaware of peripheral injury
• Autonomic neuropathy


  Promotes urinary retention (retention means stasis, promoting development of infection)
• Colonisation of skin and mucosa

  • S. aureus
  • Candida species
• Impairment of the immune response

  • Diabetes reduces chemotaxis, adherence, phagocytosis, opsonisation and increased apoptosis
  • Decreased complement
  • Decreased cytokines
  • Decreased cell mediated immunity