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Infectious Diseases
General Principles of Infectious Diseases
- Infectious diseases are disorders caused by organisms — such as bacteria, viruses, fungi or parasites. Many organisms live in and on our bodies. They're normally harmless or even helpful. But under certain conditions, some organisms may cause disease.
- Some infectious diseases can be passed from person to person. Some are transmitted by insects or other animals. And you may get others by consuming contaminated food or water or being exposed to organisms in the environment.
- Signs and symptoms vary depending on the organism causing the infection, but often include fever and fatigue. Mild infections may respond to rest and home remedies, while some life-threatening infections may need hospitalization.
- Many infectious diseases, such as measles and chickenpox, can be prevented by vaccines. Frequent and thorough hand-washing also helps protect you from most infectious diseases. Categories of Infectious Agents Taxonomic Category Size (^) Propagation Site(s) Example(s) Disease(s) Prions <20 nm Intracellular Prion protein Spongiform encephalopathies Viruses 20 – 300 nm Obligate intracellular Poliovirus Poliomyelitis Bacteria 0.2– 15 μm Obligate intracellular Chlamydia trachomatis Trachoma, urethritis Extracellular Streptococcus pneumoniae Pneumonia Facultative intracellular Mycobacterium tuberculosis Tuberculosis Fungi 2 – 200 μm Extracellular Candida albicans Thrush Facultative intracellular Histoplasma capsulatum Histoplasmosis 6
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Protozoa^1 –^50 μm^ Extracellular^ Trypanosoma gambiense^ Sleeping sickness Facultative intracellular Trypanosoma cruzi Chagas disease Obligatory intracellular Leishmania donovani Kala-azar Helminths^3 mm^ – 10 m^ Extracellular^ Wuchereria bancrofti^ Filariasis Intracellular Trichinella spiralis Trichinosis Transmission and Dissemination of Microbes Transmission of infections can occur by contact (direct and indirect), respiratory droplets, fecal- oral route, sexual transmission, vertical transmission from mother to fetus or newborn, or insect/arthropod vectors. A pathogen can establish infection if it possesses virulence factors that overcome normal host defenses or if the host defenses are compromised. i) Routes of Entry of Microbes: Host defenses against infection include: Skin: tough keratinized barrier, low pH, fatty acids Respiratory system: alveolar macrophages and mucociliary clearance by bronchial epithelium, IgA Gastrointestinal system: acidic gastric pH, viscous mucus, pancreatic enzymes and bile, defensins, IgA, and normal flora Urogenital tract: repeated flushing and acidic environment created by commensal vaginal flora ii) Spread and Dissemination of Microbes within the Body To enter the body, microbes penetrate epithelial or mucosal barriers. Infection may remain localized at the site of entry or spread to other sites in the body. Some extracellular bacteria, fungi, and helminths secrete lytic enzymes which destroy tissue and allow direct invasion. For example, Staphylococcus aureus secretes hyaluronidase, which degrades the extracellular matrix between host cells. Most common microbes spread through the lymphatics or bloodstream (either freely, e.g. Staphylococcus aureus or within inflammatory cells, e.g. Mycobacterium tuberculosis). Invasive microbes initially follow tissue planes of least resistance and drain to regional lymphatics. S. aureus may travel from a localized abscess to the draining lymph nodes. This can sometimes lead
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Pathology of some common infectious diseases
- Bacterial infections: Pneumonia, Diphtheria, Whooping cough, Tuberculosis, Syphilis, Tetanus, Plague
- Viral infections: Measles, Mumps, Herpes, AIDS, COVID-19, Dengue, Chikungunya
- Parasitic infections: Malaria, Filariasis, Giardiasis.
Pneumonia
Pneumonia is a form of acute infection of the lungs characterized primarily by inflammation of the alveoli due to filling of the alveolar air spaces with inflammatory cells and exudate which makes breathing painful and limits oxygen intake. Pneumonia can be caused by viruses, bacteria or fungi. Pneumonia accounts for 18% of all deaths of children under five years old worldwide. Classification of Pneumonia Pneumonia: Types based on Origin i. Community acquired pneumonia (CAP): When pneumonia is developed in the community (not in a hospital). CAP is the most common type of pneumonia. Most common bacteria: Streptococcus pneumonia ii. Nosocomial pneumonia (Hospital acquired pneumonia): When pneumonia is developed after admission in a hospital. Most common bacteria: Staphylococcus aureus Pneumonia: Types based on site of infection i. Lobar pneumonia: Affects a large and continuous area of the lobe of a lung. The most common organisms: Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. ii. Bronchopneumonia: Acute inflammation of the walls of the bronchioles. Characterized by multiple foci of isolated and acute consolidation. The bronchopneumonia pattern has been associated with hospital-acquired pneumonia, and with specific organisms such as Staphylococcus aureus, Klebsiella, E. coli, and Pseudomonas. Pneumonia: Types based on pathogens i. Typical pneumonia/pneumonia: Typical pneumonia is a pneumonia caused by the more traditional pathogens ( Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis ). Patient tends to become sick quickly and develops a high fever and has difficulty breathing.
ii. Atypical pneumonia/walking pneumonia: Atypical pneumonia is not caused by one of the more traditional pathogens (other than Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis ). This is usually caused by Mycoplasma (a type of bacteria without a cell wall) and Chlamydias (intracellular parasites). It is called “atypical” because the symptoms differ from those of pneumonia due to other common bacteria. Sign and symptoms of pneumonia
- Most people who develop pneumonia initially have symptoms of a cold:
- Sneezing
- sore throat
- Cough
- These symptoms are then followed by
- cough with sputum production (discolored and sometimes bloody)
- high fever (sometimes as high as 104^0 F)
- shaking chills
- feeling of being short of breath
- chest pain that is often made worse by coughing
- feeling very tired or weak Pathogenesis of pneumonia The causative agent or organism gains entry into the body through the respiratory tract by way of inspiration or aspiration of oral secretions. The invading organism starts to multiply and release damaging toxins. Once in the lungs, bacteria may invade the spaces between cells and between alveoli, where the macrophages and neutrophils attempt to inactivate the bacteria. The neutrophils also release cytokines, causing a general activation of the immune system. This leads to the fever, chills, and fatigue common in bacterial pneumonia. Soon the airless state of the lungs is changed to a consolidated state due to the fluid and exudate filling up. Filling up the lung's alveoli with fluid hinder oxygenation. Treatment of pneumonia Antibiotic is the mainstay of pneumonia treatment. Community acquired pneumonia:
- In the UK , empiric treatment with amoxicillin is recommended as the first line for community-acquired pneumonia, with doxycycline or clarithromycin as alternatives.
another reason. For people whose immune systems are weak, especially those with HIV infection, the risk of developing TB disease is much higher than for people with normal immune systems. Signs and Symptoms of tuberculosis Common symptoms:
- chest pain
- coughing up blood
- productive, prolonged cough for more than 3 weeks. Systemic symptoms include:
- Fever
- chills (coldness)
- night sweats
- appetite loss
- weight loss
- pallor (unnatural color of skin)
- fatigue (loss of strength or energy) Testing for TB Infection There are two kinds of tests that are used to determine if a person has been infected with TB bacteria: Tuberculin skin test and TB blood tests. A positive TB skin test or TB blood test only tells that a person has been infected with TB bacteria. It does not tell whether the person has latent TB infection (LTBI) or has progressed to TB disease. Other tests, such as a chest x-ray and a sample of sputum, are needed to see whether the person has TB disease. Pathogenesis of tuberculosis Once in the lung, the bacilli are phagocytosed by alveolar macrophages. Internalization of the bacilli triggers a pro-inflammatory response and leads to the recruitment of mononuclear cells from neighboring blood vessels. These monocytes form the cellular matrix of the early granuloma, which is the primary characteristic of this disease. In its early stage, the granuloma has a core of infected macrophages enclosed by foamy macrophages and other mononuclear phagocytes, surrounded by lymphocytes. As the granuloma matures, it develops an extensive fibrous capsule that encases the macrophage core and excludes the majority of lymphocytes from the center of the structure. In a progressive infection, the caseous, necrotic center of the granuloma liquefies and cavitates, spilling thousands of infectious Mycobacterium into the airways. This damage to the lungs triggers the development of a productive cough, which facilitates generation of the infectious aerosol and completion of the bacterium's life cycle.
Treatment of tuberculosis a) Treatment for Latent TB Infection: People with latent TB infection are often prescribed treatment to prevent them from developing TB disease. The four treatment regimens use isoniazid, rifapentine, or rifampin: (1) Isoniazid: 9 months (2) Isoniazid: 6 months (3) Isoniazid and Rifapentine: 3 months (4) Rifampin: 4 months Due to the reports of severe liver injury and deaths, it recommends that the combination of rifampin and pyrazinamide should generally not be offered for the treatment of latent TB infection. b) Treatment for TB Disease: There are 10 drugs currently approved by the U.S. Food and Drug Administration (FDA) for treating TB. Of the approved drugs, the first-line anti-TB agents that form the core of treatment regimens (total 6 to 9 months’ treatment) include:
- Initial phase (2 months): (1) Isoniazid, (2) Rifampin, (3) Pyrazinamide and (4) Ethambutol (Ethambutol can be discontinued if drug susceptibility studies demonstrate susceptibility to first- line drugs)
- Continuation Phase (4 to 7 months): (1) Isoniazid (2) Rifampin c) Prevention: Vaccination
- BCG, or Bacille Calmette-Guerin , is a vaccine for tuberculosis (TB) disease given at any time from birth to 15 days of life. It is to be given to all children as part of EPI schedule as recommended by the Govt. of Bangladesh. isoniazid ri fa p en tine ri fam p i n py ra zina mi de exam but I
Signs and symptoms of Covid- 19 Pathophysiology of Covid- 19 The virus invades and enters the type 2 alveolar epithelial cells via the host receptor ACE-2 and starts to undergo replication to produce more viral Nucleocapsids. The virus-laden pneumocytes now release many different cytokines and inflammatory markers such as interleukins (IL-1, IL-6, IL-8, IL-120 and IL-12), tumour necrosis factor-α (TNF-α), IFN-λ and IFN-β, CXCL10, monocyte chemoattractant protein-1 (MCP-1) and macro phage inflammatory protein-1α (MIP- 1α). This ‘cytokine storm’ acts as a chemoattractant for neutrophils, CD4 helper T cells and CD cytotoxic T cells, which then begin to get sequestered in the lung tissue. These cells are responsible for fighting off the virus, but in doing so are responsible for the subsequent inflammation and lung injury. The host cell undergoes apoptosis with the release of new viral particles, which then infect the adjacent type 2 alveolar epithelial cells in the same manner. Due to the persistent injury caused by the sequestered inflammatory cells and viral replication leading to loss of both type 1 and type 2 pneumocytes, there is diffuse alveolar damage eventually culminating in an acute respiratory distress syndrome
