复旦大学：《医学微生物学 Medical Microbiology（MBBS）》课程讲义_讨论稿_02 Encephalitis and Meningitis：Pathogens, Pathogenesis or Symptoms

Encephalitis and Meningitis: Pathogens, Pathogenesis or Microorganisms that can be spread via the bloodstream. Pathogenesis Prevention Steven Zhang 10301016055 Zara kim10301016062 North10301016042 Cathy Yu10301016071 Tony Guo10301016034

Encephalitis and Meningitis: Pathogens, Pathogenesis or Symptoms Microorganisms that can be spread via the bloodstream. Pathogenesis & Prevention Steven Zhang Zara kim North Cathy Yu 10301016055 10301016062 10301016042 10301016071 Tony Guo10301016034

Encephalitis Encephalitis is an acute inflammation of the brain 7. 4 cases per 100, 000 population in Western countries, 6. 34 per 100, 000 population and tropical countries per year. Common symptoms include headache, fever, confusion, drowsiness, and fatigue with more serious symptoms ranging from seizures/convulsions tremors, hallucinations, and memory problems. Several common causes of encephalitis are the Japanese encephalitis virus, the West Nile virus and cryptococcus neoformans

Encephalitis Encephalitis is an acute inflammation of the brain. 7.4 cases per 100,000 population in Western countries, 6.34 per 100,000 population and tropical countries per year. Common symptoms include headache, fever, confusion, drowsiness, and fatigue with more serious symptoms ranging from seizures/convulsions, tremors, hallucinations, and memory problems. Several common causes of encephalitis are the Japanese encephalitis virus, the West Nile Virus, and Cryptococcus neoformans. • • • •

Meningitis Meningtitis is inflammation of the protective membranes covering the brain and the spinal cord (meninges Bacterial infections occur in 3 people per 100, 000 and 10.9 per 100, 000 for viral infections in Western countries More common in places where people live together for th e first time Typical symptoms consist of nuchal rigidity, sudden hig h fever, and altered mental status. Streptococcus pneumonia, Neisseria meningitides, and LCMV are common microbes that lead to meningitis

Meningitis Meningtitis is inflammation of the protective membranes covering the brain and the spinal cord (meninges) Bacterial infections occur in 3 people per 100,000 and 10.9 per 100,000 for viral infections in Western countries. More common in places where people live together for th e first time. Typical symptoms consist of nuchal rigidity, sudden hig h fever, and altered mental status. Streptococcus pneumonia, Neisseria meningitides, and LCMV are common microbes that lead to meningitis. • • • • •

Japanese encephalitis virus Mosquito-borne, incubation period of 5 to 15 days, but only 1 in 25 0 infections develop into encephalitis Signs which develop during the acute encephalitic stage include neck rigidity, cachexia, hemiparesis, convulsions and a raised bod temperature between 38 and 41 degrees Celsius Generally much higher in children. Transplacental spread has been n oted. Lifelong neurological defects such as deafness, emotional abi lity and hemiparesismay occur in those who have had central nervous system involvement Increased microglial (immune cells of the CNS) activation follows J kin-infection, Activated microglia secrete cytokines, such as interleu 1(IL-1) and tumor necrosis factor alpha (tNF-a), which can cause toxic ef fects in he brain, as well as neurotoxins, excitatory neurotransmitters prostaglandin, reactive oxygen, and nitrogen species In a nonregenerating organ such as brain, a dysregulated innate imm une response would be deleterious

Japanese Encephalitis Virus Mosquito-borne, incubation period of 5 to 15 days, but only 1 in 25 0 infections develop into encephalitis Signs which develop during the acute encephalitic stage include neck rigidity, cachexia, hemiparesis, convulsions and a raised bod y temperature between 38 and 41 degrees Celsius Generally much higher in children. Transplacental spread has been n oted. Lifelong neurological defects such as deafness, emotional abi lity and hemiparesismay occur in those who have had central nervous system involvement Increased microglial (immune cells of the CNS) activation follows J EV infection, Activated microglia secrete cytokines, such as interleu kin-1(IL-1) and tumor necrosis factor alpha (TNF-α), which can cause toxic ef fects in the brain, as well as neurotoxins, excitatory neurotransmitters, prostaglandin, reactive oxygen, and nitrogen species In a nonregenerating organ such as brain, a dysregulated innate imm une response would be deleterious. • • • • •

West nile virus Incubation period is usually between 2 to 15 days Mosquitoes which are the prime vector, with birds being the most commonly infected animal and serving as the prime reser voir host. Also found in found in various species of ticks, mamm reptiles, and amphibians Not all susceptible hosts develop sufficient levels to trans mit the disease to uninfected mosquitos 80% of West nile virus infections in humans are subclinical causing no symp toms Most common symptom is the west nile fever but 1% of the cases result in neurological disease, such as west nile enc cephalitis Similar symptoms to other viral encephalitis with fever, hea daches, and altered mental status. however, there is also m muscular d weakness(30-50%), with lower motor neuron symptoms, flacci

West Nile Virus Incubation period is usually between 2 to 15 days Mosquitoes which are the prime vector, with birds being the most commonly infected animal and serving as the prime reser voir host. Also found in found in various species of ticks, mamm als, reptiles, and amphibians Not all susceptible hosts develop sufficient levels to trans mit the disease to uninfected mosquitos 80% of West Nile virus infections in humans are subclinical, causing no symptoms Most common symptom is the west nile fever, but 1% of the cases result in neurological disease, such as west nile enc ephalitis Similar symptoms to other viral encephalitis with fever, hea daches, and altered mental status, however, there is also m uscular weakness (30-50%), with lower motor neuron symptoms, flacci d • • • • • •

Lymphocytic choriomeningitis rus Spread by the common mouse, as mice can become chronically infected by maintaining the virus in their blood, as well a s vertical transmission Humans can be infected through inhalation, ingestion, and ex posure to open cuts and wounds Onset typically occurs 1 to 2 weeks after exposure, and the initial phase' s common symptoms include fever, lack of appe tite headache, muscle aches, malaise, nausea, and/ or vomiting Meningitis or encephalitis occurs in the second phase, sever al days after the recovery of the initial phase. Pathological findings during the first stage consist of leuk openly and thrombocytopenia. During the second phase, typical find ngs include elevated protein levels, increased leukocyte count r a decrease in glucose levels of the cerebrospinal fluid

Lymphocytic Choriomeningitis Virus Spread by the common mouse, as mice can become chronically infected by maintaining the virus in their blood, as well a s vertical transmission. Humans can be infected through inhalation, ingestion, and ex posure to open cuts and wounds Onset typically occurs 1 to 2 weeks after exposure, and the initial phase’s common symptoms include fever, lack of appe tite, headache, muscle aches, malaise, nausea, and/or vomiting. Meningitis or encephalitis occurs in the second phase, sever al days after the recovery of the initial phase. Pathological findings during the first stage consist of leuk openia and thrombocytopenia. During the second phase, typical find ings include elevated protein levels, increased leukocyte count, or a decrease in glucose levels of the cerebrospinal fluid. • • • • •

Streptococcus pneumonia Gram-positive, alpha-hemolytic, aerotolerant anaerobic member of the genus streptococcus Normally found in the nasopharynx of 5-10% of healthy adults, and 20-40% of healthy children The organism causes many types of pneumococcal infections other than pneumonia These include acute sinusitis, otitis media, meningitis, bacteremia, sepsis, osteomyelitis, septic arthritis, endocarditis, peritonitis, pericarditis, cellulitis, and brain abscess S. pneumoniae is one of the most common causes of bacterial meningitis in adults and young ad ults, along with Neisseria meningitidis, and is the leading cause of bacterial meningitis in adult the usa Attaches to nasopharyngeal cells through interaction of bacterial surface adhesins. This norm achi, Colonization can become infectious if the organisms are carried into areas such as the Eust tube or nasal sinuses where it can cause otitis media and sinusit The organisms polysaccharide capsule makes it resistant to phagocytosis, and if there is no occi. bre-existing anticapsular antibody, alveolar macrophages cannot adequately kill the pneumo The organism spreads to the blood stream and is carried to the meninges, joint spaces, bone Has several virulence factors: the polysaccharide capsule, that help it evade a hosts immune system, a pneumococcal surface proteins that inhibit complement-mediated opsonization, and se cretion of IgAl protease that will destroy secretory iga produced by the body and mediates its attach ent to respiratory mucosa

Streptococcus pneumonia Gram-positive, alpha-hemolytic, aerotolerant anaerobic member of the genus Normally found in the nasopharynx of 5-10% of healthy adults, and 20-40% of healthy children The organism causes many types of pneumococcal infections other than pneumonia. These include acute sinusitis, otitis media, meningitis, bacteremia, sepsis, osteomyelitis, septic arthritis, endocarditis, peritonitis, pericarditis, cellulitis, and brain abscess is one of the most common causes of bacterial meningitis in adults and young ad ults, along with , and is the leading cause of bacterial meningitis in adults in the USA Attaches to nasopharyngeal cells through interaction of bacterial surface adhesins. This norm al colonization can become infectious if the organisms are carried into areas such as the Eust achian tube or nasal sinuses where it can cause otitis media and sinusitis. The organism's polysaccharide capsule makes it resistant to phagocytosis, and if there is no pre-existing anticapsular antibody, alveolar macrophages cannot adequately kill the pneumoc occi. The organism spreads to the blood stream and is carried to the meninges, joint spaces, bone s, and peritoneal cavity, and may result in meningitis, brain abscess, septic arthritis, or osteom yelitis. Has several virulence factors: the polysaccharide capsule, that help it evade a host's immune system, a pneumococcal surface proteins that inhibit complement-mediated opsonization, and se cretion of IgA1 protease that will destroy secretory IgA produced by the body and mediates its attachm ent to respiratory mucosa. • • • • • • • Streptococcus S. pneumoniae Neisseria meningitidis

Neisseria meningitides referred to as meningococcus, appears as a gram-negative diplococcus and test po sitive for cytochrome c oxidase exists as normal flora in the nasopharynx of up to 5-15% of adults, infects the host cell by sticking to it using Trimeric Autotransporter Adhesins Meningococci only infect humans, and is the only form of bacterial meningitis kn own to occur epidemically N. meningitidis exploits host cell signaling pathways to promote its uptake by h ost cells, induced by the type Iv pili, which are the main means of meningococcal 1 adhesion onto host cells. Formation of microvilli-like structures at the site of the bacterial-cell interaction then occurs, which trigger the internalization n of the bacteria into host cells A ma jor consequence of these signaling events is a reorganization of the actin c ytoskeleton, which leads to the formation of membrane protrusions, engulfing bac terial pathogens into intracellular vacuoles. Efficient internalization of N. me ningitidis also requires the activation of an alternative signaling pathway coup led with the activation of thetyrosine kinase receptor erbB2. Beside Type Iv pil 1, other outer membrane proteins may be involved in other mechanism of bacteria internalization into cell Initially produces general symptoms like fatigue, it can rapidly progress from f ever, headache and neck stiffness to coma and death ong with a notable non-b1 aching purpuric rash

Neisseria meningitides referred to as meningococcus appears as a Gram-negative diplococcus and test po sitive for cytochrome c oxidase exists as normal flora in the nasopharynx of up to 5-15% of adults, infects the host cell by sticking to it using Trimeric Autotransporter Adhesins Meningococci only infect humans, and is the only form of bacterial meningitis kn own to occur epidemically exploits host cell signaling pathways to promote its uptake by h ost cells, induced by the type IV pili, which are the main means of meningococca l adhesion onto host cells. Formation of microvilli-like structures at the site of the bacterial-cell interaction then occurs, which trigger the internalizatio n of the bacteria into host cells. A major consequence of these signaling events is a reorganization of the actin c ytoskeleton, which leads to the formation of membrane protrusions, engulfing bac terial pathogens into intracellular vacuoles. Efficient internalization of also requires the activation of an alternative signaling pathway coup led with the activation of thetyrosine kinase receptor ErbB2. Beside Type IV pil i, other outer membrane proteins may be involved in other mechanism of bacteria internalization into cells Initially produces general symptoms like fatigue, it can rapidly progress from f ever, headache and neck stiffness to coma and death, along with a notable non-bl anching purpuric rash • • • • • • , N. meningitidis N. me ningitidis

Brief introduction of bacteria found in bloodstream Several types of bacteria live on the surface of the skin or colonize the moist linings of the urinary tract, lower digestive tract, and other internal surfaces. These bacteria are normally harmless as long as they are kept in check by the body's natural barriers and the immune syst People in good health with strong immune systems rarely develop bacteremia. However, when bacteria are introduced directly into the circulatory system, especially in a person who is ill or undergoing aggressive medical treatment, the immune system may not be able to cope with the invasion, and symptoms of bacteremia may develop Common immediate causes of bacteremia include drainage of an abscess, including an abscessed tooth urinary tract infection, especially in the presence of a bladder catheter decubitus ulcers (pressure sores) intravenous procedures using unsterilized needles, including Iv drug use prolonged IV needle placement

Brief Introduction of Bacteria found in Bloodstream. Several types of bacteria live on the surface of the skin or colonize the moist linings of the urinary tract, lower digestive tract, and other internal surfaces. These bacteria are normally harmless as long as they are kept in check by the body ' s natural barriers and the immune system. People in good health with strong immune systems rarely develop bacteremia. However, when bacteria are introduced directly into the circulatory system, especially in a person who is ill or undergoing aggressive medical treatment, the immune system may not be able to cope with the invasion, and symptoms of bacteremia may develop. Common immediate causes of bacteremia include: drainage of an abscess, including an abscessed tooth urinary tract infection, especially in the presence of a bladder catheter decubitus ulcers (pressure sores) intravenous procedures using unsterilized needles, including IV drug use prolonged IV needle placement • • • • • • • u

General pathogenesis and Prevention Bacteremia is diagnosed by culturing the blood for bacteria. Samples may need to be tested several times over several hours. blood analysis may also reveal an elevated number of white blood cells. Blood pressure is monitored closely:a decline in blood pressure may indicate the onset of septic shock Bacteremia may cause no symptoms, but may be discovered through a blood test for defects or whose immune systems are suppressed as those with heart valvet in another condition. In this situation, it may not need to be treated, except in patients especially at risk for infection, such Prognosis Prompt antibiotic therapy usually succeeds in clearing bacteria from the bloodstream. Recurrence may indicate an undiscovered site of infection. Untreated bacteria in the blood may spread, causing infection of the heart (endocarditis or pericarditis)or infection of the covering of the central nervous system (meningitis) Prevention Bacteremia can be prevented by preventing the infections which often precede it. developing bacterial infection. Treating bacterial infections quickly and p Good personal hygiene, especially during viral illness, may reduce the risk of thoroughly can minimize the risk of spreading infection. During medica duration of invasive procedures, to reduce patients' exposure to sources of and procedures, the burden falls on medical professionals to minimize the number bacteria when being treated, and to use scrupulous technique

General Pathogenesis and Prevention Bacteremia is diagnosed by culturing the blood for bacteria. Samples may need to be tested several times over several hours. Blood analysis may also reveal an elevated number of white blood cells. Blood pressure is monitored closely; a decline in blood pressure may indicate the onset of septic shock. Bacteremia may cause no symptoms, but may be discovered through a blood test for another condition. In this situation, it may not need to be treated, except in patients especially at risk for infection, such as those with heart valve defects or whose immune systems are suppressed Prompt antibiotic therapy usually succeeds in clearing bacteria from the bloodstream. Recurrence may indicate an undiscovered site of infection. Untreated bacteria in the blood may spread, causing infection of the heart (endocarditis or pericarditis) or infection of the covering of the central nervous system (meningitis). Bacteremia can be prevented by preventing the infections which often precede it. Good personal hygiene, especially during viral illness, may reduce the risk of developing bacterial infection. Treating bacterial infections quickly and thoroughly can minimize the risk of spreading infection. During medical procedures, the burden falls on medical professionals to minimize the number and duration of invasive procedures, to reduce patients' exposure to sources of bacteria when being treated, and to use scrupulous technique. • • • • Prognosis Prevention