Describe the normal flora and the host-parasite relationship including virulence factors and host defences.

Normal Flora

• Beneficial roles — colonisation resistance (competing for nutrients and receptors and producing inhibitory substances), synthesis of vitamin K and B group vitamins, stimulation of the immune system and of gut-associated lymphoid tissue, and aid to digestion
• Harmful roles — they act as opportunistic pathogens when displaced from their site (E. Coli in the urinary tract), when a barrier is breached (bowel perforation, a catheter), or when immunity fails; and they are a reservoir of resistance genes

Host-parasite Relationship

Determinants of Bacterial Virulence

• Adhesion — pili and fimbriae, adhesins and surface proteins; without attachment there is no infection, which is why the flushing action of urine and the mucociliary escalator are so protective
• Invasion — invasins and enzymes: hyaluronidase ("spreading factor"), collagenase, streptokinase (fibrinolysin), lecithinase
• Evasion of host defences — the capsule (antiphagocytic); protein A of staphylococci (binds the Fc portion of IgG the wrong way round); M protein of Streptococcus pyogenes; IgA protease; coagulase, which walls the organism off in fibrin; intracellular survival (Mycobacterium, Salmonella, Listeria); and antigenic variation
• Toxin production — exotoxins and endotoxin
• Iron acquisition by siderophores, competing with host transferrin and lactoferrin
• Biofilm formation on devices and damaged tissue

Host Defence Mechanisms

• Mechanical barriers — intact skin, mucous membranes, the mucociliary escalator, coughing and sneezing, the flushing of urine and tears
• Chemical barriers — gastric acid, lysozyme in tears and saliva, fatty acids and low pH of skin, lactoferrin, defensins, the acidic vaginal pH
• Biological — the normal flora itself
• Innate cellular and humoral — phagocytes (neutrophils and macrophages), natural killer cells, the complement system, interferons, acute phase proteins, fever and inflammation
• Adaptive — humoral (antibody) and cell-mediated immunity, with memory

Koch Postulates and Their Limitations

• The postulates — the organism must be found in all cases of the disease and not in healthy individuals; it must be isolated in pure culture; it must reproduce the disease when inoculated into a susceptible animal; and it must be RE-isolated from that animal
• Limitations — some organisms cannot be cultured (M. Leprae, Treponema pallidum); some have no animal model; asymptomatic carriers harbour the organism without disease, breaking the first postulate; disease may require several organisms or a particular host state; and ethical considerations forbid human inoculation
• Modified molecular postulates now relate a gene to virulence — the gene should be present in pathogenic strains, its inactivation should reduce virulence, and restoring it should restore virulence
• They remain a useful discipline of thought — before attributing a disease to an organism, ask whether it is present in all cases, absent in health, and capable of producing the illness

Applied Aspects

• Distinguish colonisation from infection before prescribing — a positive wound swab, sputum culture or catheter urine in a well patient usually needs no antibiotic, and treating it selects resistance
• Every indwelling device breaches a barrier; catheters, cannulae and tubes should be removed as soon as they are not needed, which prevents more infection than any antibiotic
• Immunosuppressed patients are threatened by their own flora and by organisms of low virulence, so the differential diagnosis of fever is entirely different
• Chronic carriers sustain outbreaks — the typhoid carrier with gallbladder colonisation is the classical example, and food handlers must be identified and treated
• Do not suppress gastric acid unnecessarily; it is a genuine defence, and its removal increases enteric infection, C. Difficile and pneumonia
• Handwashing removes transient flora and is the single most effective measure against cross-infection; alcohol rub is faster and better for most organisms, but soap and water is required for C. Difficile spores
• Resident flora cannot be eliminated, only reduced, which is why surgical scrub uses a substantive agent such as chlorhexidine that goes on acting under the glove
• Probiotics aim to restore the flora, and faecal microbiota transplantation for recurrent C. Difficile infection is a striking demonstration that the flora itself can be therapeutic
• The microbiome is increasingly implicated beyond infection — in obesity, immune development and inflammatory disease — which reframes the normal flora as an organ rather than a set of passengers
• Opportunistic infection defines the differential in the immunosuppressed — organisms of low virulence that would never trouble a normal host, so the threshold for investigation must be far lower
• Malnutrition, diabetes, HIV and chronic kidney disease are the common causes of impaired defence in Indian practice, and each shifts the likely pathogens in a predictable direction
• Virulence and host resistance are two sides of one balance; the same organism causes asymptomatic carriage in one person and fatal sepsis in another, which is why treating the host matters as much as killing the organism
• Vaccination works by shifting that balance before exposure, and is the only intervention that prevents infection without selecting for resistance
• Nutrition is an underrated determinant of infection outcome, and in India undernutrition remains a major reason why tuberculosis, measles and diarrhoea kill children who would otherwise recover
• Splenectomised patients are at lifelong risk from capsulated organisms — pneumococcus, meningococcus and Haemophilus — and require vaccination, prophylaxis and a card, because the spleen is what clears them
• Take an occupational, travel and animal contact history; brucellosis, leptospirosis, scrub typhus, anthrax and rabies are all suggested by exposure long before any test is available