Infectious Disease PDF

Infectious disease 09/11/2024 18:46 Definition: Infectious disease can be detected when causing pathological effects to tissues and cells. It is caused by an agent that is contagious or can transmit and cause an infection. Determining the cause of the pathology is important fo...

Infectious disease 09/11/2024 18:46 Definition: Infectious disease can be detected when causing pathological effects to tissues and cells. It is caused by an agent that is contagious or can transmit and cause an infection. Determining the cause of the pathology is important for: - Diagnosis - Treatment - Prognosis - Prevention (control of disease) An infectious disease can be passed easily from one person to another, especially through air and water. A infectious disease has causative agent. This causative agent is microscopic called microorganism or microbes. Etiological agents are substances that contain infectious microorganism. An infection is when there is damage to tissues or cells leading to symptomatic disease. Causes of infectious disease can be: - Bacteria (prokaryotes) - Viruses (non-cellular) - Fungi (eukaryotes) - Protozoa (eukaryotes) - Prions (proteins, non-cellular) - Helminths (non-microbial, eukaryotes) - Arthopods (non-microbial, eukaryotes) Archaea don’t have any infectious agent identified till now however possible role in periodontal disease. Each of these microorganism have their own distinctive characteristics such as organism type, replicative processes, structural and molecular composition, genetics which determines how they interact with the host and causes disease. Routes of transmission - Aerosol, by inhalation of air droplets containing microorganism - Oral, by ingestion of contaminated food or water - Direct contact with infected individual tissue or bodily fluid, via entry sites such as eyes, mouth, nose wound such as bite, scratch - Fomite transmission contaminated surfaces of inanimate objects such as cages, door, handles, medical equipment - Vector-borne by other living organisms such as mosquitoes and ticks - Zoonotic originating from other animal species through routes above Transmission of disease causing agents Infectious agents must be transmitted between hosts Transmission of infectious agents in multiple different routes Routes are related to specific types of microorganism and the type of tissue or cell it can infect. For example, rhinoviruses causing the common cold infect the respiratory tract and are dispersed through coughing and sneezing Transmitted in air borne droplets of sputum and mucus Droplets are inhaled by another person and can then infect the respiratory tract of this individual Bacillus anthracis Gram positive bacilli that form endospore. They are present in the environment, in soils and water and contaminated animal products e.g. wool, hides or hair Occurs globally Key factors causing disease are capsule (poly-D-glutamic acid (γDPGA) capsule) and two toxins which are lethal factor and Edema factor. Depending on the transmission route it may cause: - Cutaneous anthrax - Gastrointestinal anthrax - Inhalation anthrax - Injection anthrax: resulting from needles administered drug use - Welder's anthrax Cutaneous anthrax Around 95% cases Contamination of wound with spores from environment or contaminated animal products or injury e.g., biting insect. Disease onset 1-6 days from exposure. Symptoms, typical black eschar, swelling, skin ulcer with black centre, systemic disease 20% fatality rate if untreated 100% survival with treatment Gastrointestinal anthrax Ingestion of spores from meat from an animal infected with anthrax Symptoms: diarrhoea or bloody diarrhoea, stomach pain, swelling of abdomen (stomach), headache, fainting, flushing (red face) and red eyes >50% fatality rate if untreated 60% survive if treated Inhalation anthrax Breathing in of spores from contaminated animal products Onset of disease 1 week- 2 months Symptoms: fever and chills, sweating, headache, body ache, cough, chest discomfort, shortness of breath, nausea, vomiting or stomach pains, extreme tiredness 100% fatality rate if untreated 55% survive if treated Injection contracted anthrax From needles contaminated with soil or material, swelling at the injection site, nausea and vomiting and sweats. Welders anthrax (B. cereus group that makes anthrax toxin)- pneumonia diagnosis with symptoms that included fever or chills, cough, shortness of breath (dypnea), and coughing up blood (hemoptysis). Pathologies and transmission of Bacillus anthracis Spores germinate at site, often in low oxygen areas Macrophages phagocyte spores Bacilli containing macrophages spread into lymph system. The capsule of the bacteria prevents vegetative cells phagocytosis (prevents immune system from destroying them). Toxins: - Edema toxin, lethal factors (adenylate cyclase increases intracellular levels of cyclic AMP (cAMP)) and protective antigen (binds to cell) - Lethal toxin, zinc metalloprotease results in hyperinflammation via MAPKK (mitogen- activated protein kinase kinase) ROS and proinflammatory cytokines like TNF-alpha and IL-1beta Bacilli can enter bloodstream and cause septicaemia (10^7 to 10^8 organisms per millilitre of blood), and spread to the brain and meninges and also cause pulmonary blockage. Routes of transmission : RTI agents Many microorganisms can spread via inhalation of air droplets containing microorganism. Airborne pathogens Upper respiratory tract: - Staphylococcus aureus - Neisseria meningitidis - Streptococcus pyogenes - Corynebacterium diphtheriae - Haemophilus influenzae - Common cold virus - Mycoplasma increase - Pneumoniae decrease Lower respiratory tract: - Influenza virus - Mycobacterium tuberculosis - Coccidioides immitis - Bordetella pertussis - Streptococcus pneumoniae - Pneumonia viruses - Coxiella burnetii - Chlamydophila pneumoniae How can infectious disease be characterised? Infectious diseases were discovered due to medical practitioners trying to work out why certain diseases spread, how to treat them and how to prevent them. They are defined by their Signs: e.g. fever, coughing and vomiting Symptoms e.g. pain and nausea Pathology of an infectious disease determines the signs and symptoms resulting in the syndrome Influenza syndrome It is an infectious disease Its causative agent is influenza virus, and this virus has genome made of segmented negative sense single stranded RNA (ssRNA). It has pleomorphic nucleocapsid (flexible). Signs and symptoms - Fever - Cough - Sore throat - Congestion - Muscle/body aches - Fatigue - Vomiting and diarrhoea Influenza is the Italian word for the Latin word influentia meaning influence. Characteristics of infectious disease - Phases of an infectious disease - Duration of infectious disease - Location of infectious disease - Timing of infectious disease - Stages in infection Phases of infectious disease Incubation period; time between infection and the appearance of signs and symptoms Prodromal phase; mild, non-specific symptoms that signal onset of some diseases Clinical phase; a person experiences typical signs and symptoms of disease Decline phase; subsidence of symptoms Recovery phase; symptoms have disappeared, tissues heal, and the body regains strength By duration - Acute disease Develops and progresses quickly Example: Ebola (Ebola haemorrhagic fever) Symptoms onset around 5-9 days Early symptoms are fever and fatigue Later symptoms are vomiting, diarrhoea, rash, haemorrhaging, bleeding or bruising - Chronic disease Develops slowly and less severe but long lasting Example: Human Papilloma virus (HPV), genital warts, oropharyngeal cancers Asymptomatic, transformation of cells to malignant carcinoma takes around 10 years Modelling to suggest by 2120 >60 million deaths averted in low-. Low-middle income countries. - Latent disease Characterised by no symptoms between outbreak and illness Examples: Herpes Simplex Virus HSV1, HSV2 HSV1 oral-oral, HSV2 sexually transmitted infection Blisters/ulcers at site of infection, reoccur sporadically Spread to central nervous system, state of quiescence in neuron nucleus. By location - Local disease Confined to a specific area of the body Example: Ringworm (tinea): Trichophyton, microsporum, and epidermophyton fungal species Caused by a dermatophyte (temp 27-33 degree C) Affects 25% population 4-14 days onset. - Systemic Infects across multiple body sites and across tissues. By timing - Primary, initial infection in a previously healthy person - Secondary, infection that occurs in a person weakened by a primary infection Primary infection Example: Human Immunodeficiency Virus (HIV) It is a virus with positive ssRNA genome, with an enveloped capsid. It spreads via bodily fluids. Around 80% patients experience flu-like illness symptoms 2-6 weeks after infection, including fever, sore throat, body rash. HIV infects CD4+ T cells in the gut mucosa. It also infects thymus which causes failure to regenerate more T cells. HIV infects cells in the secondary lymph nodes leading T cells depletion. (decrease in T cells) Chronic inflammatory response reduces T cell function impaired haematopoiesis Secondary infection When immune system is weakened other infections can occur such as: - Mycobacterium tuberculosis - Taxoplasma gondii- protist - PML JC virus (JCV) polyomavirus (50-60%) - Cytomegalovirus - Cryptococcus neoformans or, C. gattii Pathogenesis of infectious disease How infectious agents cause disease Mechanisms of pathogenicity depend on infecting pathogen For example: - Production of poisons such as toxins and enzymes that destroy cells and tissue for example often produced by bacteria - Direct invasion and destruction of host cells for example viruses and some bacteria - Triggering responses from the host's immune system leading to disease signs and symptoms for example fever, sneezing, vomiting triggering by the immune system to rid the body of the pathogen. Steps in infection Entry and attachment to the body and overcome innate immune response. After attaching it begins colonisation, local or/and general spread through the body, invasion into tissues and cells. It goes through replication require for multiplication. Access and obtain necessary nutrients/cellular machinery for replication and evade immune response Exit (shedding from body), leave site or sites for onward transmission. The pathology and damage to the host may result of the above processes Immune response may contribute to the disease pathology resulting from the blocking, deactivating and clearing of infecting microorganism. Some pathological effects of disease may be caused by more than one causative agent Some shared pathology by site of infection: - Respiratory infections - Bloodstream infections - Encephalitis (inflammation of the brain) - Meningitis (inflammation of the lining around brain and spinal cord) - Endocarditis (infection of the heart) - Gastrointestinal disease - Skin and soft tissue infections Example: skin and soft tissue Mucocutaneous lesions Abscess formation- infection and inflammation of hair follicles Spreading infections Necrotizing infections Skin manifestations by systemic infections Skin infections from direct contant Impetigo site of infection is epidermis and causative agent is streptococcus pyogenes and/or staphylococcus aureus Erysipelas, site of infection is dermis and causative agent is S. pyogenes. Folliculitis, Boils, Carbuncles are the infections, site of infection is hair follicles and causative agents is S. aureus. Cellulitis is the infection, site of infection is subcutaneous fat and causative agent is S. pyogenes. Necrotizing fascilitis, site of infection is fascia, causative agents are anaerobes/polymicrobial/S. pyogenes. Gangrene, site of infection is muscle and causative agent is clostridium perfringens Example: skin and soft tissue Spreading infections Direct introduction of microbe into epithelium Papilloma microbe grows in epithelium, which proliferates, microbe shed with epithelial cells (wart). Macule (flat, red) local inflammation immune response infiltrating leukocytes Papule (raised, red) more marked inflammation (invasion of neighbouring tissue) Vesicle (small blister) microbe invades epithelium- HSV, VZV. Ulcer epithelium ruptures, microbe discharged- HSV, VZV, yaws. Skin manifestations by systemic infections An exit and shedding resulting in disease pathology Arrival of circulating microbe Microbes exit from blood vessel, invasion of neighbouring dermal cells Macule (flat, red) Local inflammation immune response infiltrating leukocytes. Papule (raised, red) more marked inflammation (invasion of neighbouring tissue) Vesicle (small blister) microbe invades epithelium- HSV, VZV. Ulcer epithelium ruptures, microbe discharged- HSV, VZV, yaws. Arrival of circulating toxin (e.g. scarlet fever) or immune complex (e.g. hepatitis B) Skin disease from systemic infections, may shed bacteria Skin manifestation Disease/Infection Agent A ‘Rose spots’ containing Enteric fever Salmonella typhi bacteria B Petechial/maculopapular Septicaemia, Neisseria meningitidis lesions containing bacteria meningitis C Ecthyma gangrenosum, skin Septicaemia Pseudomonas aeruginosa lesion D Dissemination rash Syphilis/Yaws Treponema pallidum, T. pertenue E Macular or haemorrhagic rash Rocky Mountain Rickettsia prowazekii, Rickettsia Spotted Fever typhi, Rickettsia rickettsii F Rash caused by erythrogenic Scarlet fever S. pyogenes toxin Enteric Fever: S. Typhi Gram negative bacteria Human specific. Symptoms: - High fever - Headache - Nausea - Abdominal pain - Constipation - Diarrhoea Uses Vi capsule to attach to human cells. This capsule contains N-acetylneuraminic acid (Neu5Ac) sialoglycan that helps it stick to and infect cells. Primary infection, secondary infection and carrier state (no symptoms but still carry and spread bacteria). Low initial immunological response- regulation of Vi Capsule fimbrae. Acute typhoid fever Cellular response Elevated anti-Vi antibody Decreased zinc concentration Decreased platelets and lymphocytes (anemia) Markers of liver damage shown by levels of alpha1-antitrypsin. Diagnosis - Clinical presentation of symptoms - Laboratory detection to confirm presence of S.Typhi Treatment Antimicrobial drugs Antibiotics Antivirals Antifungals Prevention - Vaccines - Good hygiene and sanitation - Protection against vector e.g. mosquitoes/ticks - Isolation or quarantine of patients Treatment of infectious diseases Antibiotics - Only works against some bacteria and do not work against viruses or other agents - Target bacteria-specific structures/functions in the prokaryote cell: - Resistance of bacteria increasing globally (AMR) - CDC identified 18 infectious agents that are of concern. $4.6 billion annually. Antiviral drugs - Work against some viruses - Block parts of viral replication, e.g. nucleotide incorporation Antifungal drugs - Challenging to develop due to eukaryotic nature of cells targeting/parasitic life cycle Prevention Vaccines - Vaccines consist of either weakened, inactivated or dead or components of the microorganism. - Work by stimulating the body's immune system to fight off future infection - Vaccination programmes successfully eradicated smallpox - Global led campaigns to tackle polio Influenza Caused by influenza viruses Can be acute and highly contagious via airborne transmission/indirect contact. It affects respiratory tract but symptoms are caused throughout body. Epidemics occurs seasonally, typically with low fatality. Pandemics are more deadly and happen less frequent. Genome structure means it is highly changeable and infect multiple species like humans, pigs and birds. Concerns for avian flu lead to new pandemic H1n! And H5N1. Epidemiology is the science that examines patterns causes and effects of disease (not just infectious disease) on the health of a given population. Goal is to control and reduce incidence of disease via identification of factors that are cause disease, transmission of disease and help prevent/ reduce future disease. To identify these factors epidemiologists can breakdown into four branches - Disease aetiology (causing agent) - Outbreak investigation - Disease screening and surveillance - Comparisons of treatment or effects (clinical trials) Reducing spread of infectious disease Removal of infectious agent - Good personal hygiene and sanitation - Basic measures for frequent and thorough handwashing to limit spread of disease Protection against vector (physical barriers/chemical treatments) E.g. mosquitoes against Malaria and West Nile virus E.g. ticks to prevent Lyme disease Quarantine (physical separation to prevent transmission) Covid-19 and Ebola as recent examples to physically stop transmission occurring. Diagnosis - Signs and symptoms - Detection of microorganism - Pathology- diagnostic histopathology Molecular pathology Immunohistochemistry In situ hybridization probes (genome and the transcriptome on formalin fixed paraffin embedded (FFRE) tissues). Assess the tissue reaction induced by an infectious organism and lesion characteristics Associate morphologically recognised lesions with the presence of an infectious agent To determine the type of inflammatory reaction (e.g. fibrinous, purulent, lymphocytic, and granulomatous) associated with a specific microbe. Diagnosis using microscopy Stain for microorganisms Leprosy- M. leprae, Ziehl-Neelson Histoplasma, Histoplasmosis, Gomori Grocott Crystococcus, Acian blue. Syphillis- Treponema pallidum, Warthin starry Immunohistochemistry for microorganism Tissue stain such as Hematoxylin and Eosin with antibodies for microorganism. A: Cutaneous Leishmaniasis (anti-Leishmania antibody) protozoa B: Lymph node histoplasmosis (anti- Histoplasmosis antibody) C: Cutaneous Cryptococcus (anti-Cryptococcus antibody) D: Gastric syphillis - (anti-Treponema antibody) E: Simian Vacuolating virus 40 (anti-SV40) in brain tissue F: Lymph node infection HIV (anti-p24 antibody) – capsule protein) Other methods for microorganism Tissue samples with in situ hybridization (ISH), electron miscroscopy (EM) A: Head and neck carcinoma (human papillomavirus, ISH, original magnification ×500). B simian vacuolating virus 40 (SV40) infection in cerebral tissue (SV40, ISH, original magnification ×360). C Interaction between Bacillus anthracis (arrows) and an endothelial cell (asterisks) from a pulmonary capillary (arrowheads: capsule remnants of the bacteria) (EM, original magnification ×5400). Other methods for microorganism Tissue samples with molecular biology (PCR) D (1–3) Infection of the lung due to tularemia. Histology revealed extensive inflammation with granulomatous ( D3 PCR assay for tularemia DNA (arrow)s) and an endothelial cell (asterisks) Diagnostic histopathology laboratory involvement Uses in emerging infectious diseases such as Zika, initial investigation of HIV and AIDS Observations of associated pathologies contribute to understanding in pathogenic effects/mechanisms of disease by aetiological agents Limitations are availability of specific antibodies, possibility to be replaced by genomics Emerging infectious diseases Emerging diseases are those that have recently appeared within a population, or incidence in increasing rapidly Can re-emerge Acquisition of resistance of antimicrobial drugs, e.g. MDR Neisseria gonorrhoeae— ceftriaxone last resort Vaccine or preventative measures ineffectual (e.g. measles) Appearance of a previously unknown agent Spread of an infectious agent to a new host Spread of an infectious agent to new locations summary Infectious diseases can result in pathological disease Varied and diverse causes of infectious diseases Determining the causative agent permits treatment and helps aid prevention ○ Considerations around detection and causation of infection versus asymptomatic carriage ○ Also insights from microbiota studies examining health and disease states Diagnosis may need combination of signs, symptoms, clinical diagnosis (detection of microorganism/toxin/antibody), and epidemiological insight Infectious disease management