Clinical Immunology BMLS 3051 - Infectious Diseases Lesson 10 PDF

CLINICAL IMMUNOLOGY BMLS 3051 Lesson #10 a: Infectious Diseases Selected Infectious Diseases – Pathogens; clinical presentations and diagnostic aspects Rabies virus Hepatitis A virus (HAV) Hepatitis B virus (HBV) Hepatitis C virus (HCV) Neisseria meningitidis Bacillus anthracis Vibrio cholerae Myc...

CLINICAL IMMUNOLOGY BMLS 3051 Lesson #10 a: Infectious Diseases Selected Infectious Diseases – Pathogens; clinical presentations and diagnostic aspects Rabies virus Hepatitis A virus (HAV) Hepatitis B virus (HBV) Hepatitis C virus (HCV) Neisseria meningitidis Bacillus anthracis Vibrio cholerae Mycobacterium tuberculosis Rabies – Rhabdovirus (bullet shaped) affecting the CNS After a bite or other rabies exposure, the rabies virus has to travel to the brain before it can cause symptoms The incubation period may last for weeks to months. The incubation period may vary based on the location of the exposure site (how far away it is from the brain), the type of rabies virus, and any existing immunity. Rabies – Rhabdovirus (bullet shaped) affecting the CNS Typical representation of the pathogenesis of rabies virus, where the virus infects the brain and leads to encephalitis, the virus also moves out and infects most other organs especially salivary glands, skin, mucosal surfaces and gut  Rabies – clinical presentation The first symptoms of rabies may be very similar to those of the flu including general weakness or discomfort, fever, or headache. Discomfort or a prickling or itching sensation at the site of the bite may follow, progressing within days to acute symptoms of cerebral dysfunction, anxiety, confusion, and agitation. As the disease progresses, the person may experience delirium, abnormal behavior, hallucinations, hydrophobia (fear of water), and insomnia. The acute period of disease typically ends after 2 to 10 days. Once clinical signs of rabies appear, the disease is nearly always fatal To date less than 20 cases of human survival from clinical rabies have been documented Rabies The rabies virus infects the central nervous system (CNS) If a person does not receive the appropriate medical care after a potential rabies exposure, the virus can cause disease in the brain, ultimately resulting in death. Rabies can be prevented by vaccinating pets, staying away from wildlife, and seeking medical care after potential exposures before symptoms start. Rabies – Intervention & test NB: To avert symptoms most patients receive a treatment called human rabies immunoglobulin (HRIG). This is given the day the bite occurred. To determine whether or not the animal had rabies -A special test called immunofluorescence is used to look at the brain tissue after an animal is dead. Time is of the essence!!! Infectious Diseases – Hepatitis: Focus on HAV, HBV and HCV) (a) Hepatitis is inflammation of the liver resulting from a variety of root causes. It can cause jaundice. (b) Jaundice is characterized by yellowing of the skin, mucous membranes, and sclera of the eyes. (credit b left: modification of work by James Heilman, MD; credit b right: modification of work by “Sab3el3eish”/Wikimedia Commons) Infectious Diseases – Hepatitis Hepatitis A virus (HAV) is a member of the genus hepatovirus. HAV is a non-enveloped ssRNA(+) virus It is the most common cause of viral hepatitis in the United States. Transmission is by the fecal-oral route, and the virus is shed in the feces. A common mode of transmission of the virus is through eating uncooked shellfish harvested from sewage-contaminated water. Transmission via blood is rare. Infectious Diseases – Hepatitis A (“infectious hepatitis”) Although the five hepatitis viruses differ, they can cause some similar signs and symptoms because they all have an affinity for hepatocytes (liver cells). HAV infections are most commonly seen among children, especially those living in crowded accommodations such as summer camps. The main site of replication is the hepatocyte, where infection results in severe cytopathology, and liver function is severely impaired. The prognosis for patients with HAV is generally favorable, and development of persistent infection and chronic hepatitis is uncommon Infectious Diseases – Hepatitis A (“infectious hepatitis”) - Pathogenesis The virus enters the blood (viremia), spreading to the spleen, the kidneys, and the liver. During viral replication, the virus infects hepatocytes. The inflammation is caused by the hepatocytes replicating and releasing more hepatitis virus. Signs and symptoms include malaise, anorexia, loss of appetite, dark urine, pain in the upper right quadrant of the abdomen, vomiting, nausea, diarrhea, joint pain, and gray stool. Additionally, when the liver is diseased or injured, it is unable to break down hemoglobin effectively, and bilirubin can build up in the body, giving the skin and mucous membranes a yellowish color, a condition called jaundice In severe cases, death from liver necrosis may occur. Infectious Diseases – Hepatitis A (“infectious hepatitis”) –Prevention Vaccines prepared from whole virus inactivated with formaldehyde are now available. Immune globulin has been used for many years, mainly as post exposure prophylaxis. Prevention of HAV infection also requires taking measures to avoid fecal contamination of food and water  Infectious Diseases – Hepatitis B Transmission is generally associated with exposure to infectious blood or body fluids such as semen or saliva. Exposure can occur through skin puncture, across the placenta, or through mucosal contact, but it is not spread through casual contact such as hugging, hand holding, sneezing, or coughing, or even through breastfeeding or kissing. Risk of infection is greatest for those who use intravenous drugs or who have sexual contact with an infected individual. Health-care workers are also at risk from needle sticks and other injuries when treating infected patients. The infection can become chronic and may progress to cirrhosis or liver failure. ****It is also associated with liver cancer.  Infectious Diseases – Hepatitis B Chronic infections are associated with the highest mortality rates and are more common in infants. Approximately 90% of infected infants become chronic carriers Vaccination is available and is recommended for children as part of the standard vaccination schedule (one dose at birth and the second by 18 months of age) and for adults at greater risk (e.g., those working with blood products, intravenous drug users, and those who have sex with multiple partners). Health-care agencies are required to offer the HBV vaccine to all workers who have occupational exposure to blood and/or other infectious materials. Infectious Diseases – Hepatitis C HCV is often undiagnosed and therefore may be more widespread than is documented. Transmitted through contact with infected blood. Although some cases are asymptomatic and/or resolve spontaneously, 75%–85% of infected individuals become chronic carriers. Nearly all cases result from parenteral transmission often associated with IV drug use or transfusions. The risk is greatest for individuals with past or current history of intravenous drug use or who have had sexual contact with infected individuals. Can even be transmitted through contaminated personal products such as toothbrushes and razors. Infectious Diseases – Hepatitis Summary  Bacterial Meningitis & Neisseria meningitidis – gram negative diplococci Bacterial meningitis is one of the most serious forms of meningitis. pathogen often gains access to the CNS through the bloodstream after trauma or as a result of the action of bacterial toxins.  Infectious Diseases – Bacterial Meningitis & Neisseria meningitidis Early symptoms include severe headache, fever, confusion, nausea, vomiting, photophobia, and stiff neck. A unique sign of meningococcal meningitis is the formation of a petechial rash on the skin or mucous membranes, characterized by tiny, red, flat, hemorrhagic lesions. Systemic inflammatory responses with some may occur. Sepsis, as a result of systemic damage from meningococcal virulence factors, can lead to rapid multiple organ failure, shock, disseminated intravascular coagulation, and death. Diagnosis of bacterial meningitis is best confirmed by analysis of CSF obtained by a lumbar puncture. Abnormal levels of polymorphonuclear neutrophils (PMNs) (> 10 PMNs/mm3), glucose (< 45 mg/dL), and protein (> 45 mg/dL) in the CSF are suggestive of bacterial meningitis.  Bacterial Meningitis & Neisseria meningitidis (a) A normal human brain removed during an autopsy. (b) The brain of a patient who died from bacterial meningitis. Note the pus under the dura mater (being retracted by the forceps) and the red hemorrhagic foci on the meninges. (credit b: modification of work by the Centers for Disease Control and Prevention)  Virulence factors of Neisseria meningitidis The pathogenicity of N. meningitidis is enhanced by virulence factors including lipo- oligosaccharide (LOS) endotoxin Type IV pili for attachment to host tissues Polysaccharide capsules that help the cells avoid phagocytosis and complement-mediated killing. Aside: Endotoxins are part of the Gram negative bacterial cell wall and are Lipopolysaccharide-protein complexes, while Exotoxins are usually heat-labile proteins that typically come from Gram-positive bacteria and are secreted.  More Virulence factors of Neisseria meningitidis Additional virulence factors include: IgA protease (which breaks down IgA antibodies) Invasion factors/adhesive proteins Opa, Opc, and porin (which facilitate transcellular entry through the blood-brain barrier) Iron-uptake factors/sequestration (which strip heme units from hemoglobin in host cells and use them for bacterial growth) Stress proteins that protect bacteria from reactive oxygen molecules. Infectious Diseases – Anthrax Bacillus anthracis B. anthracis infects primarily domestic herbivores such as sheep, goats, and horses. Infection usually occurs through contact with infected animal products or spore-contaminated dust that is inoculated through incidental skin abrasions or is inhaled. B. anthracis spores are highly resistant to physical and chemical agents, and may remain viable for many years in contaminated pastures or animal materials. B. anthracis produces two plasmid-coded exotoxins: edema factor, which causes elevation of intracellular cAMP leading to severe edema, and lethal factor, which causes additional adverse effects. The B. anthracis capsule is essential for full virulence. Anthrax - Bacillus anthracis 1. Cutaneous anthrax - Upon introduction of organisms or spores that germinate, a papule develops. It rapidly evolves into a painless, black, severely swollen “malignant pustule”, which eventually crusts over. The organisms may invade regional lymph nodes, and then the general circulation, leading to a fatal septicemia. The overall mortality rate in untreated cutaneous anthrax is about twenty percent. 2. Pulmonary anthrax (“wool-sorter’s disease”)Caused by inhalation of spores, this disease is characterized by progres-sive hemorrhagic pneumonia and lymphadenitis (inflammation of the lymph nodes), and has a mortality rate approaching 100 percent if untreated. 3. Gastrointestinal form of anthrax - this unusual form of anthrax is caused by ingestion of spores, for example, by eating raw or inadequately cooked meat containing B. anthracis spores. This is the portal of entry commonly seen in animals Anthrax - Bacillus anthracis Treatment: B. anthracis is sensitive to penicillin, doxycycline and ciprofloxacin. However, these antibiotics are effective in cutaneous anthrax only when administered early in the course of the infection. Prevention: Because of the resistance of endospores to chemical disinfectants, autoclaving is the only reliable means of decontamination. A cell-free vaccine is available for workers in high-risk occupations. Anthrax - Bacillus anthracis- anthrax as a weapon https://www.cdc.gov/anthrax/bioterrorism/threat.html Letters lined up for collection or delivery If a bioterrorist attack were to happen, Bacillus anthracis, the bacteria that causes anthrax, would be one of the biological agents most likely to be used. Biological agents are germs that can sicken or kill people, livestock, or crops. Anthrax is one of the most likely agents to be used because: Anthrax spores are easily found in nature, can be produced in a lab, and can last for a long time in the environment. Anthrax makes a good weapon because it can be released quietly and without anyone knowing. The microscopic spores could be put into powders, sprays, food, and water. Because they are so small, you may not be able to see, smell, or taste them. Anthrax has been used as a weapon before. Anthrax has been used as a weapon around the world for nearly a century. In 2001, powdered anthrax spores were deliberately put into letters that were mailed through the U.S. postal system. Twenty-two people, including 12 mail handlers, got anthrax, and five of these 22 people died.  Tuberculosis – Mycobacterium tuberculosis Mycobacterium tuberculosis. Acid-fast rods; not colored by Gram stain due A. Acid-fast stain of sputum from a patient with tuberculosis. B. Typical to lipid-rich cell walls; long, slender, non- growth pattern showing “cording” motile (that is, growing in strings). rods Aerobic Resistant to drying Culture M. tuberculosis on specialized medium such as Lowenstein-Jensen agar Active pulmonary tuberculosis shedding of large numbers of organisms by coughing, creating aerosol droplets Resistant to dessication - the organisms remain viable in the environment for a long time. mode of contagion is person-to-person transmission by inhalation of the aerosol, and repeated or prolonged contact is usually required for transmission of infection. A single infected person can pass the organism to numerous people in an exposed group, such as a family, classroom, or hospital ward  Tuberculosis – Mycobacterium tuberculosis Pathogenicity and Immunity After being inhaled, mycobacteria reach the alveoli, where they multiply in the pulmonary epithelium or macrophages. Within two to four weeks, many bacilli are destroyed by the immune system, but some survive and are spread by the blood to extrapulmonary sites. The virulence of M. tuberculosis - Immunity: M. tuberculosis stimulates both a humoral its ability to survive and grow and a cell-mediated immune response. Circulating within host cells when antibodies do not convey resistance engulfed by macrophages, Instead, cellular immunity (CD4+ T cells) and the accompanying delayed bacterial sulfolipids inhibit the hypersensitivity directed against a number of bacterial fusion of protein antigens, develop in the course of infection, and phagocytic vesicles with contribute to both the pathology of and immunity to the disease. lysosomes. *The ability of M. tuberculosis to grow even in immunologically activated macrophages and to remain viable within the host for decades, are  Tuberculosis – Mycobacterium tuberculosis Laboratory identification/Diagnosis Diagnosis of active pulmonary tuberculosis includes demonstration of clinical symptoms and abnormal chest radiographs (fibrosis), and confirmation by isolation of M. tuberculosis from relevant clinical material example sputum. Acid-fast bacilli using techniques such as the Ziehl-Neelsen stain is the most rapid test for mycobacteria. A definitive identification of M. tuberculosis can only be obtained by culturing the organism, or by using molecular methods/biochemistry Two to eight weeks are required to culture the tubercle bacillus because of its slow growth on laboratory media Mycobacterium tuberculosis colonies grown on LowensteinJensen medium. Cholera – Vibrio cholerae V. cholerae, serogroup O1 strains are associated with epidemic cholera Short, curved, rod-shaped organisms Rapidly motile by means of a single polar flagellum. Vibrios are facultative anaerobes, halophiles (salt-loving) Cholera – Vibrio cholerae: Epidemiology V. cholerae is transmitted by contaminated water and food There are no known animal reservoirs, or animal or arthropod vectors. Among humans, long-term carriage is considered uncommon There are two biotypes (subdivisions) of the species, V. cholerae: Classic and El Tor In contrast to the classic strain, the El Tor strain is distinguished by the production of hemolysins, higher carriage rates and the ability to survive in water for longer periods Outbreaks of both strains have been associated with raw or undercooked seafood harvested from contaminated waters Cholera – Vibrio cholerae: pathogenesis (intoxication) Following ingestion, V. cholerae infects the small intestine. The organism is noninvasive, and causes disease through the action of an enterotoxin that initiates an outpouring of fluid Adhesion factor(s) are important for colonization and virulence. Cholera toxin is a multimeric protein composed of an A and a B subunit. The B subunit (consisting of five identical monomers) binds to the GM1 ganglioside receptor of cells lining the intestine. The A subunit penetration of the cell membrane, ribosylates the membrane- bound Gs protein. Gs protein activates adenylate cyclase, which produces elevated levels of intracellular cAMP. This, in turn, causes an outflowing of ions and water to the lumen of the intestine Cholera – Vibrio cholerae Full-blown cholera is characterized by massive loss of fluid and electrolytes from the body. After an incubation period ranging from hours to a few days, profuse watery diarrhea (rice-water stools) begins Untreated, death from severe dehydration causing hypovolemic shock may occur in hours to days, and the death rate may exceed fifty percent. Patients with suspected cholera need to be treated prior to laboratory confirmation, because death by dehydration can occur within hours. NB: Treatments that lessen gastric acidity, greatly reduce the infectious dose. Cholera – Vibrio cholerae – Laboratory Identification V. cholerae grows on standard media such as blood and MacConkey agars. Thiosulfate–citrate–bile salts–sucrose (TCBS) medium can enhance isolation. The organism is oxidase-positive, but further biochemical testing is necessary for specific identification of V. cholerae THANK YOU