Lecture 3: Infections of the Respiratory and Gastro-intestinal Tract PDF

Lecture 3 Infections of the Respiratory and Gastro-intestinal Tract Dr. Claire Atkinson The respiratory system is the most commonly infected system Health care providers will see more respiratory infections than any other type Caused by many types of infectious agents and on occasion multiple agents...

Lecture 3 Infections of the Respiratory and Gastro-intestinal Tract Dr. Claire Atkinson The respiratory system is the most commonly infected system Health care providers will see more respiratory infections than any other type Caused by many types of infectious agents and on occasion multiple agents at the same time A major portal of entry for airborne pathogens It is divided into 2 tracts (upper & lower) Different infections are associated with both The upper respiratory tract: Nasal cavity, sinuses, pharynx, and larynx Infections are fairly common Usually nothing more than an irritation The lower respiratory tract: Lungs and bronchi Infections are more dangerous Can be very difficult to treat Upper continuously exposed Lower essentially sterile Respiratory pathogens Common pathogens include bacteria and viruses Less common are fungi and helminths Respiratory pathogens are easily transmitted from human to human They circulate within a community Infections spread easily Some respiratory pathogens exist as part of the normal flora, these can be disrupted via viral infections, antibiotics, injury, invasive testing Others are acquired from animal sources—zoonotic infections Q fever from farm animals Psittacosis from parrots and other birds Respiratory pathogens Water can be a source of respiratory infections Legionellosis Contaminated water can be aerosolized, inhaled and infection can result Fungi are also a source of respiratory infection, yeast and moulds e.g candida spp are normal flora of the URT Usually in immunocompromised patients Most dangerous are Aspergillus and Pneumocystis Cause problems with diagnosis, due to overgrowth Some pathogens are restricted to certain sites e.g. Legionella in the lung Other pathogens cause infection in multiple sites e.g. Streptococcus Pharyngitis – sore throats Many are relatively mild, short-lived and do not require laboratory investigations e.g. viral infection (rhinovirus, coronavirus, adenovirus). If they are severe and longer lasting they warrant lab investigation. A classic infection is strep throat Caused by Streptococcus pyogenes (Group A Strep) Streptococcus pyogenes can cause scarlet fever and toxic shock syndrome Pharyngitis – sore throats Virulence factors of streptococcus Acute coughs Usually viral. Unlikely to require any laboratory investigations. If longer-lasting and associated with fever, with or without production of purulent sputum, it may suggest progression to a more serious lower respiratory infection warranting lab investigation. If the patient (usually a young child) has a characteristic ‘whoop’ sound when coughing, it may indicate Bordetella pertussis (‘Whooping cough’) which is a notifiable disease PERTUSSIS - (WHOOPING COUGH) Highly contagious – airborne spread Infects 80–100% of exposed susceptible individuals Spreads rapidly in schools, hospitals, offices, and homes—just about anywhere Caused by Bordetella pertussis Gram-negative coccobacillus Does not survive in the environment – human is the only reservoir Part of childhood vaccination programme Whenever possible, clinicians should obtain an Perinasal swab or aspirate from all persons with suspected pertussis. Respiratory infection with airway obstruction Most common in infants and young children trachiobronchitis or bronchioloitis. Most commonly caused by viruses such as respiratory syncytial virus RSV, parainfluenza virus, meta-pneumovirus and generally diagnosed by detection of pathogen nucleic-acids by polymerase chain reaction (PCR). https://www.itv.com/watch/news/study-finds-new-vaccine-for-rsv-couldreduce-child-hospitalisations-by-83percent/869mfnc Respiratory infection with airway obstruction Airway obstruction could also be due to epiglottitis. This is most commonly caused by Haemophilus influenzae but is usually diagnosed clinically. Airway obstruction could also be due to diphtheria (caused by Corynebacterium diphtheriae, which may require laboratory investigation. Both H. Influenza and diptheria have been dramatically reduced by vaccination. Diptheria now extremely rare in developed parts of the world Lower respiratory tract infection e.g pneumonia Usually diagnosed clinically by physician observation and chest X-ray but laboratory investigation is required to confirm aetiology and determine most appropriate anti-infective treatment. Productive cough (purulent sputum) – likely to be bacterial infection (Streptococcus pneumoniae, Haemophilus influenzae, Staph aureus, Pseudomonas aerugenosa or Klebsiella pneumoniae. Can also be caused by other organisms such as Legionella Lower respiratory tract infection e.g pneumonia Non-productive (‘dry’) cough – likely to be caused by a virus or so-called ‘atypical’ bacteria (Mycoplasma pneumoniae, Chlamydia,pneumoniae, Legionella pneumophila). May require laboratory investigation. Chronic cough with generalised symptoms (weight loss) - Should investigate for tuberculosis. Respiratory infections in people that have other chronic respiratory conditions (e.g. cystic fibrosis) and or immuno-deficiencies, or people who have lived in or travelled to certain geographical locations, should consider non-classical pathogens such as pneumocystis pneumonia Bacterial Pneumonia One of the most serious lower respiratory tract infections divided into 2 types: Nosocomial pneumonia Occurs approximately 48 hours after admission to hospital Usually associated with Staphylococcus aureus Also caused by Gram-negative bacteria Particularly difficult to deal with if pathogen is resistant to antibiotics Community-acquired pneumonia Usually presents as a lobar pneumonia Accompanied by fever, chest pain, and production of purulent sputum NOSOCOMIAL PNEUMONIA: Pathogenesis Figure 21.11b Strelkauskas' Microbiology: A Clinical Approach, 3e (© CRC Press 2024) Aspiration pneumonia – major problem in hospital patients Figure 21.11a Strelkauskas' Microbiology: A Clinical Approach, 3e (© CRC Press 2024) Microbiology:Microbiology: Strelkauskas' A Clinical Approach, A Clinical by Approach Tony Srelkauskas (3rd Edition) © Garland © CRCScience Press ISBN: 978-0-8153-6514-3 Lower respiratory tract infection e.g pneumonia Don’t forget about SARS-CoV-2! https://www.science.org/doi/10.1126/science.abc6156 Respiratory tract samples URTI throat swabs and nasopharageal swabs LRTI Sputum sample of choice Swabs or aspirates in small children Respiratory samples such as sputum need to be pre-treated before they are suitable for culture why do we need to pre-treat some samples? Lower respiratory tract samples Sputum sample of choice Swabs or aspirates in small children Respiratory samples such as sputum need to be pre-treated before they are suitable for culture why do we need to pre-treat some samples? Some samples contain ‘normal flora which can be diluted out to make pathogen detection more likely Samples from sterile sites may require concentration to be able to detect pathogen Lower respiratory tract samples Rember UK SMI Microscopy/ culture/ sensitivity S pneumoniae is the most common cause of community acquired pneumonia has a distinctive appearance on Gram stain (Gram + diplococci) , however needs to be confirmed Lower respiratory tract samples Culture / molecular techniques PCR for viral targets H. influenza and S pneumoniae require enriched C02 incubation PCR is it an RNA or DNA virus? Lower respiratory tract samples Factor X &V required for growth of H. influeza Maldi-TOF Mycobacteria Cell wall contains high concentration of lipid (mycolic acid) – aiding resistance to antibiotics/ disinfectants/ impermeability of stains Tuberculosis is the most significant mycobacterial disease An estimated 2 billion people are infected AIDS and HIV infection have had a significant role in the increase of tuberculosis. Poverty and poor socioeconomic conditions are breeding grounds for tuberculosis Drug resistance is becoming increasingly dangerous A major reason for resistance is noncompliance - many patients stop taking the drugs early Initial symptoms are similar to those seen in other respiratory infections—it is important to look for: Fever, Fatigue, Weight loss, Chest pain, Shortness of breath, Congestion with coughing Tuberculosis Two basic types of tuberculosis Primary Follows initial exposure to the pathogen, most likely to occur in children and the immunocompromised Secondary Can occur years later when dormant TB becomes reactivated (various sites, spread via lymphatic system) Many people in the West have contracted TB while visiting countries with a high rate of TB Diagnosis of Tuberculosis Drug resistant TB Multidrug resistant tuberculosis (MDRTB) Resistant to Isoniazid and Rifampin Rifampin resistance associated with mutations in the rpoB gene XDR-TB - extremely drug resistant Resistant to 2nd line such as amikacin plus quinolone Respiratory viruses The respiratory viruses that most commonly circulate in all continents as endemic or epidemic agents are influenza virus respiratory syncytial virus parainfluenza viruses RNA Viruses Metapneumovirus Rhinovirus Coronaviruses Adenoviruses Bocaviruses DNA Viruses Diagnosis is via reverse-transcription real- time PCR (RNA) or RT-PCR (DNA) Often run in multiplex Outbreaks of seasonal RSV/ Influenza every year. Monitored by UKHSA Respiratory viruses The respiratory viruses that most commonly circulate in all continents as endemic or epidemic agents are influenza virus respiratory syncytial virus parainfluenza viruses RNA Viruses Metapneumovirus Rhinovirus Coronaviruses Adenoviruses Bocaviruses DNA Viruses Diagnosis is via reverse-transcription real- time PCR (RNA) or RT-PCR (DNA) Often run in multiplex Outbreaks of seasonal RSV/ Influenza every year. Monitored by UKHSA Respiratory Syncytial Virus Enveloped RNA virus; Paramyxoviridae family Causes season outbreaks of respiratory illness (Oct – March) The very young (under 1 year of age) and the elderly are at the greatest risk infants aged less than 6 months frequently develop the most severe disease such as bronchiolitis and pneumonia, which may result in hospitalisation. Children born prematurely, or with underlying chronic lung disease, and the elderly with chronic disease are also at increased risk of developing severe disease. Highly infectious 80% of children have had the virus by the age of 2 in the UK Respiratory Syncytial Virus Approximately 2–3% of children with a primary RSV infection in the first 12 months of life require hospitalization and 2–6% of them are admitted to Intensive Care In one trial published in the New England Journal of Medicine in April, the Pfizer RSV vaccine given during pregnancy was shown to be effective against severe RSV-associated lower respiratory tract illness in infants up to six months old. Respiratory Syncytial Virus Sanofi in partnership with AstraZeneca have developed a new long acting monoclonal Beyfortus® (nirsevimab) for passive immunisation against RSV infection and disease Nirsevimab was licensed by the Medicines and Healthcare products Regulatory Agency (MHRA) on 9 November 2022. Pfizer have developed a bivalent RSV prefusion F maternal vaccine candidate, RSVpreF which has undergone clinical trials and has a potential licensing timeline in 2024. QUESTIONS? QUESTIONS? The most appropriate sample to take from a patient with a lower respiratory tract infection is? Select one: A. Throat wab B. Blood culture C. Sputum D. Saliva E. Nasal swab A perinasal swab can be collected and used to diagnose Bordetella pertussis infection? Select one A. B. True False QUESTIONS? Lancefield grouping is used for the classifying? Select one A. Staphylococci B. Streptococci C. Neisseria D. Clostridium E. Mycobacterium Infections of the Gastro-intestinal Tract The GI tract is essentially a long tube, ascending from the mouth to the anus. It is a very sophisticated delivery system for nutrients, comprising 8 main sections, supplemented by 4 accessory organs. The 8 main components are the; mouth pharynx oesophagus stomach small intestine large intestine rectum anus FIGURE 10.1 Diagram of the human gastrointestinal tract. Host Defences The GI tract is heavily colonised with microorganisms and viruses and encounters millions of new ones every day. Because of this, defences against infection are extremely important. All intestinal surfaces are coated with layers of mucus, which provides mechanical protection. Secretory IgA and phagocytes can be found lining the gut Muscular surfaces of the GI tract ensures movement termed peristalsis. Various fluids in the GI tract also have antimicrobial properties. Saliva lysozyme and lactoferrin; stomach fluid is antimicrobial through the virtue of its extremely low pH (pH 1.5-3.0) Normal flora is also vitally important to prevent infection Dysbiosis can be caused by antibiotic chemotherapy, illness, pregnancy, or dietary changes. Gastroenteritis Gastroenteritis (inflammation of the lining of the stomach and intestines) is characterised by diarrhoea and/or vomiting Depending on the cause of the infection, the symptoms of gastroenteritis can take from a few hours to a few days after exposure to develop Most cases resolve without treatment within days, although persistent or severe symptoms may occur which may require hospitalisation and treatment Gastroenteritis- diarrhoea This may be defined as stools of a loose or liquid consistency occurring more frequently than is normal for the individual. Due to: multiplication of pathogens in the gut ingestion of pre-formed toxins in food, produced by bacteria toxin production in the large intestine by toxin producing bacteria Acute - diarrhoea Often a symptom of foodborne or waterborne illness This can be after a short incubation period 1-2 hrs (ingestion of preformed toxin – ‘intoxication’) or in 2-7 days (after proliferation of the pathogen in the body – ‘infection’). Type of food eaten can give a clue to aetiology The most commonly implicated organisms are Salmonella, Campylobacter, Vibrio (‘infection’), Bacillus cereus, Clostridium perfringens, and Staphylococcus aureus (‘intoxication). Most episodes of diarrhoea are self-limiting and do not require, or benefit from, antibiotic treatment. Some infections such as shiga-toxinproducing E. coli (STEC) can be made much worse by antibiotic treatment. Acute – Bloody diarrhoea Acute bloody diarrhoea is a sudden onset of diarrhoea where obvious blood is present. Dysentery is an acute infectious gastroenteritis characterised by loose stools with blood and mucus, often accompanied by pyrexia and abdominal cramps. Organisms implicated in acute bloody diarrhoea include; bacteria: Campylobacter spp., Shigella spp., Shiga-toxin-producing Escherichia coli (STEC), including serogroup O157, and Salmonella spp. protozoa: Entamoeba histolytica. Acute – Persistent /Chronic diarrhoea Persistent is defined as diarrhoea of >14 days, but fewer than 30 days, in duration. Immune status of the patient should be considered Chronic diarrhoea is considered that which lasts >30 days. Chronic diarrhoea is a major clinical feature and a leading cause of morbidity and mortality in uncontrolled HIV infection. Organisms implicated are predominantly protozoa, such as Giardia spp., Cryptosporidium spp., Cyclospora cayetanensis and Microsporidia spp. Acute – diarrhoea with vomiting Acute diarrhoea with vomiting is often referred to as food poisoning (intoxication). It can be severe in patients especially in infants and children. Onset of symptoms is acute (1 to 4 hours). Organisms implicated include Bacillus cereus, norovirus, adenovirus, rotavirus, Vibrio spp., Staphylococcus aureus and Clostridium perfringens.. Lab diagnosis Laboratory Diagnosis Dependent upon the possible aetiology. Bacteria, viruses, protozoa, helminths Bacteria – culture on media (less commonly nucleic acid detection by PCR, antigen detection by EIA) Viruses – nucleic acid detection by PCR Protozoa & helminths – direct microscopy on faeces (less commonly nucleic acid detection by PCR, antigen detection) Remember UK SMI Campylobacter Spp Campylobacter commonly found as part of the gastrointestinal and genitourinary tract flora of animals, 90% of human cases caused by C. Jejuni, Primary reservoir is animals, modes of transmission include: Ingestion of contaminated food Direct contact with pets that harbor the organism Most common source is undercooked poultry Can also be contaminated water and unpasteurized milk Campylobacter Spp Campylobacter Selective Agar (CAMPY) is used for the selective isolation of Campylobacter jejuni.The growth of normal faecal flora is inhibited on this media. Because Campylobacter is microaerophilic, cultures must be incubated in an environment with reduced oxygen, optimally between 5 and 10 percent. The optimal temperature for growth is 42°C for C jejuni, and 37°C for many of the other enteric Campylobacter Confirmation – Maldi-TOF Salmonella Spp Second most isolated cause of bacterial gastroenteritis Two most common strains isolated in the UK are S. enteritidis and S. typhimurium Primary modes of transmission is ingestion of contaminated food, but human to human spread is also important. S. typhi and S. paratyphi known as enteric fevers: a multiorgan Salmonella infection with: Sustained bacteraemia Profound infection of organs Particularly the lymph nodes, liver, and spleen After infection bacteria can be excreted for weeks – carrier state Shigella Spp Strictly human pathogen – not found in animals Spread from person to person in unsanitary conditions 4 species exsist of which S. Sonnei is a significant cause of diarrhoeal illness in the UK Shigella species causes classical dysentery – blood/mucus in stool with abdominal cramps. Shigellosis is one of the most common causes of diarrheal worldwide S. dysenteriae causes the most severe form of infection and is usually acquitted in parts of the world with poor sanitation Salmonella/ Shigella Spp XLD agar- Xylose-lysine-desoxycholate agar Coliforms – yellow Salmonella – black Shigella - pink HarlequinTM Salmonella ABC showing typical green Salmonella colonies. These are easy to distinguish from other nonpathogens growing on the media which appear most often as black colonies. Courtesy of M. Ford. Escherichia coli E.Coli forms part of the normal gut flora or man and animals and birds. Over 150 strains E. coli strains have caused numerous and ongoing outbreaks following contamination of foods, including lettuce, sprouts, hazelnuts, and flour. E. coli O157:H7 and its close relatives are the most virulent of them all. This collection of organisms, of which this E. coli strain is the most infamous representative, are generally referred to as shiga-toxinproducing E. coli (STEC). An important virulence determinant for STEC is the ability to lesions in the large intestine. The microvilli are lost from the gut epithelium, and the lesion produce bloody diarrhoea Approx. 10% of patients develop a condition termed haemolytic uremic syndrome (HUS), a severe haemolytic anaemia that can cause kidney damage and renal failure These serious manifestations are most likely to occur in children younger than 5 years of age and in the elderly. Escherichia coli Escherichia coli CT-SMAC (Cefixime Tellurite Sorbitol MacConkey agar) Escherichia coli O157 produces colourless colonies on SMAC agar, while other Escherichia coli strains form pink colonies. O157 does not ferment sorbitol = colourless colonies Serotyping using type-specific antisera Vibrio Spp Cholera – caused by Vibrio cholerae After being ingested with contaminated food or water, V. cholerae travels through the stomach to the small intestine, where they penetrate the mucous using their flagellum, adhere to the microvilli of the epithelial cells, and multiply. The bacterium does not enter the host cells but produce an enterotoxin (cholera toxin, CT), causing intestinal cells to shed large amounts of electrolytes into the intestine, an event accompanied by profuse water loss. Fluid losses of nearly 1 litre per hour have been reported in severe cases, and an untreated patient can lose up to 50% of body weight during the course of the disease. This voided fluid contains flecks of mucus, giving the description of ‘rice-water stool’. Vibrio Spp Thioshulphate citrate bile salts (TCBS) Agar is used for the selective isolation of cholera vibrios and Vibrio parahaemolyticus from a variety of clinical and nonclinical specimens. pathogenic Vibrio spp. Clostridium difficile Clostridioides difficile is a Gram-positive, endosporeforming rod-shaped bacterium found as part of the normal intestinal biota. It is associated with a condition termed pseudomembranous colitis, due to the formation of a pseudomembrane, containing fibrin and cells resulting from dysbiosis as a result of the treatment with broadspectrum antibiotics, Is termed antibiotic-associated diarrhoea. C. difficile produces two enterotoxins, toxins A and B, that cause areas of necrosis in the wall of the intestine. The predominant symptoms is diarrhoea, with abdominal cramps, fever and leucocytosis in more severe cases Diagnsosed via toxin from faeces generally performed using enzyme immunoassay Gastritis and gastric ulcers Gastritis (inflammation of the lining of the stomach) is experienced as a sharp or burning pain emanating from the upper abdomen. Gastric or peptic ulcers are actual lesions in either the mucosa of the stomach (gastric ulcers) or the uppermost section of the small intestine (duodenal ulcers). Severe ulceration can be accompanied by bloody stools, vomiting, or both. Symptoms are often worse in the evening, after eating, or under conditions of physiological stress. Gastritis and gastric ulcers are caused by a bacterium called Helicobacter pylori. H. pylori is a curved, gram-negative rod, closely related to Campylobacter spp. Gastritis and gastric ulcers Gastritis and Gastric Ulcers Once the H. pylori passes into the GI tract, it bores through the outermost mucous layer that lines the stomach epithelium. The bacterium produces toxins that directly damage the mucosa, and also urease, converting urea to ammonium and bicarbonate, both alkaline compounds, neutralising the pH of the stomach acid. As the immune system recognises and attacks the organism, infiltrating WBC’s damage the epithelium to some degree. In some, the lesions lead to deeper erosion and ulceration, and can lead to gastric cancer Diagnosed through non-invasive breath test, detects urea. VIRAL INFECTIONS OF THE DIGESTIVE SYSTEM Table 22.6 characteristics of viruses that cause gastrointestinal infections. Table 22.6 Strelkauskas' Microbiology: A Clinical Approach, 3e (© CRC Press 2024) Microbiology:Microbiology: Strelkauskas' A Clinical Approach, A Clinical by Approach Tony Srelkauskas (3rd Edition) © Garland © CRCScience Press ISBN: 978-0-8153-6514-3 Norovirus Norovirus affects all age groups Low infective dose of