PHA211 Microbiological Basis of Disease Chapter 12 - Nervous System Infections PDF

PHA211 – Microbiological Basis of Disease Chapter 12 Nervous System Infections  Outline I. Bacteria: II. Viruses: 1. Borrelia burgdorferi 1. Arboviruses 2. Escherichia coli 2. Enteroviruses 3. Listeria monocytoge...

PHA211 – Microbiological Basis of Disease Chapter 12 Nervous System Infections  Outline I. Bacteria: II. Viruses: 1. Borrelia burgdorferi 1. Arboviruses 2. Escherichia coli 2. Enteroviruses 3. Listeria monocytogenes 3. Herpes simplex type 1 4. Neisseria meningitidis 4. Herpes simplex type 2 5. Streptococcus pneumoniae 5. HIV IV. Parasites: 6. Rabies 1. Taenia solium III. Fungi: 2. Toxoplasma gondii 1. Cryptococcus neoformans 3. Trichinella spiralis 2. Histoplasma capsulatum 4. Trypanosoma 2 Borrelia Common characteristics Long, slender, flexible, Shape spiral- or corkscrew-shaped rods Motility Highly motile (endoflagella) Gram staining (-)! Oxygen requirement Aerobes (microaerophilic) Culture Difficult & time-consuming Borrelia burgdorferi Important members Borrelia recurrentis 3  Borrelia burgdorferi  Properties:  Transmitted to humans by the bite of a small tick (genus Ixodes).  Deer, mice, other rodents & birds serve as reservoirs for the spirochete.  Not spread from human to human.  Causes the Lyme disease. 4  Borrelia burgdorferi  Transmission: o Life cycle covers 2 years during which the tick obtains 3 blood meals. o ♂ dies soon after mating. o ♀ dies after depositing their eggs in the following spring. o Variations depend on climate & food availability for the natural hosts. 5  Borrelia burgdorferi  Pathogenesis:  1st stage: spreading of organism to CNS & other tissues & organs.  2nd stage: neurologic complications such as meningitis.  3rd stage: appearance of progressive CNS disease (in small number of patients). 6  Borrelia burgdorferi  Laboratory identification:  PCR is used to assist in detection of B. burgdorferi in body fluids & provides the most definitive test.  Infection can be diagnosed serologically (but the number of false positives can out-number the true positives). 7 Escherichia Common characteristics Shape Short rods Motility Motile (if not adhesive-sedentary) Gram staining (-) Oxygen requirement Facultative anaerobes Oxidase test (-) Culture MacConkey agar Important member Escherichia coli 8  Escherichia coli  Properties:  Part of the normal flora in the colon of humans & other animals.  Species possess 3 types of antigens: O, K & H.  Pili facilitate its attachment to human epithelial surfaces.  Can be pathogenic both within & outside the GI tract.  Pathogenic “virotypes” differ from the normal flora E. coli by the acquisition of genes that encode new virulence factors  toxin production & attachment to or invasion of host cells. 9  Escherichia coli  Pathogenesis: Antigenic structure  O antigen: contained in the repeating polysaccharide units of the lipopolysaccharide (LPS) in the outer membrane of the cell wall.  K antigen: polysaccharide capsule present in some strains.  H antigen: flagellar protein. CFA = colonization factor antigens BFP = bundle-forming pili 10  Escherichia coli  Pathogenesis: Toxins  -hemolysin = a pore-forming cytotoxin that inserts into the plasma membrane of a wide range of host cells  leakage of cytoplasmic contents  cell death.  Cytotoxic necrotizing factor (CNF) = often produced in concert with - hemolysin & disrupts G proteins regulating signaling pathways in the cell cytoplasm  multiple effects (apoptosis).  Stx (Shiga toxin): the A–B toxin enters the cell  combines at ribosome sites involved with tRNA binding  interference with protein synthesis. 11  Escherichia coli  Clinical significance: i. Urinary tract infections (chapter 16). ii. Diarrhea (chapter 15). iii. Meningitis in infants. 12  Escherichia coli  Meningitis in infants:  E. coli & group B streptococci are the leading causes of neonatal meningitis.  The pathogenesis involves vaginal E. coli colonization of the infant via ruptured amniotic membranes or during childbirth.  Failure of protective maternal IgM antibodies to cross the placenta & the special susceptibility of newborns surely play a role. 13  Escherichia coli  Laboratory identification:  Cultured on differential medium such as MacConkey agar, most strains ferment lactose. 14 Listeria Common characteristics Slender, short rods, sometimes occurring as Shape diplobacilli or in short chains Motility Distinctive tumbling motility in liquid medium Gram staining (+) (staining darkly) Oxygen requirement Facultative anaerobes Catalase test (+) Property Facultative intracellular parasites Culture Facultatively on a variety of enriched media Important member Listeria monocytogenes 15  Listeria monocytogenes  Properties:  The only species that infects humans, although the Listeria species are widespread among animals in nature.  Has been used extensively to study phagocytosis & immune activation of macrophages. 16 Listeria monocytogenes An unusual feature for human pathogens is the ability of L. monocytogenes to grow slowly in the cold (even at temperatures < 0°C). Growth at refrigerator temperatures turns out to be important in the foodborne transmission of L. monocytogenes. 17  Listeria monocytogenes  Pathogenesis:  It attaches to & enters a variety of mammalian cells by phagocytosis.  Once inside the cell, it escapes from the phagocytic vacuole by producing listeriolysin O = a membrane-damaging toxin.  It grows in the cytosol & stimulates changes in cell function that facilitate its direct passage from cell to cell. 18  Listeria monocytogenes  Infections:  May occur as sporadic cases or in small epidemics  Are usually food-borne: dairy products (including ice cream & cheese), ground meats & poultry  Are most common in pregnant women, fetuses, newborns & immunocompromised individuals. 19  Listeria monocytogenes  Clinical significance: Listeriosis  Septicemia & meningitis are the most commonly reported forms of listeria infection. 20  Listeria monocytogenes  Laboratory identification:  Can be isolated from blood, CSF & other clinical specimens.  Produces a small colony surrounded by a narrow zone of -hemolysis on blood agar.  Listeria species can be distinguished by morphology, positive motility & production of catalase. 21 Neisseria Common characteristics Shape Kidney bean–shaped diplococci Motility Non-motile Gram staining (-) Oxygen requirement Aerobes Oxidase test (+) Culture Thayer-Martin or chocolate agar Neisseria gonorrhoeae Important members Neisseria meningitidis 22  Neisseria meningitidis  Properties:  One of the most frequent causes of meningitis.  13 serogroups have been defined on the basis of the antigenic specificity of their polysaccharide capsule.  Transmission is via respiratory droplets.  Pili allow the attachment of N. meningitidis to the nasopharyngeal mucosa. 23 Neisseria meningitidis N. meningitidis causes one of the few infections in which patients may progress from normal health to death in less than a day. It can also spread quickly in family, schools, institutions & military barracks. 24  Neisseria meningitidis  Pathogenesis:  Attaches to microvillus cells by outer membrane proteins (OMP) & pili.  Endocytosed in vacuoles & multiplies freely in the cytoplasm.  Escapes to the submucosa: – the gonococcus is actively phagocytosed & remains localized; – the meningococcal capsule allows it to evade phagocytosis & it enters the bloodstream. PMNs = polymorphonuclear neutrophils 25  Neisseria meningitidis  Clinical significance: 1. Meningococcemia: meningococci penetrate the nasopharynx barrier  blood stream  multiplication. 2. Meningitis: meningococci cross the blood–brain barrier  infect the meninges  acute inflammatory response  purulent meningitis. 26  Neisseria meningitidis  Laboratory identification:  Obtained from CSF, it appears as Gram(-) diplococci, often inside of & in association with polymorpho- nuclear leukocytes.  Can be cultured on chocolate agar.  Oxidase(+)  Utilizes both glucose & maltose in an atmosphere of 5% CO2. 27 Streptococci Common characteristics Ovoid to spherical Shape Occurring as pairs or chains Motility Non-motile Gram staining (+) Oxygen requirement Facultative anaerobes Catalase test (-) Culture media Blood agar Streptococcus agalactiae Important members Streptococcus pneumoniae Streptococcus pyogenes 28  Streptococcus pneumoniae  Properties:  Formerly called Diplococcus pneumoniae & referred to as "pneumococcus“.  Most common cause of pneumonia & otitis media.  Important cause of meningitis & bacteremia/sepsis.  Carried in the nasopharynx of many healthy individuals. 29  Streptococcus pneumoniae  Infection: 1. Endogenous: in a carrier who develops impaired resistance to the organism. 2. Exogenous: by droplets from the nose of a carrier.  Individuals susceptible to the infection:  Those who have a general debilitation such as that caused by malnutrition, alcoholism or respiratory damage following a prior viral infection.  Those who have a depressed immune system.  Patients with sickle cell disease.  Patients who have had their spleens removed. 30  Streptococcus pneumoniae  Pathogenesis:  Capsule: the most important virulence factor & the basis for the classification of serotypes of this organism. It is antiphagocytic.  Autolysins: peptidoglycan-hydrolyzing enzymes present in the bacterial cell wall & normally inactive. Once activated, they result in cell lysis & the release of intracellular virulence factors.  Pneumolysin: attacks mammalian cell membranes, causing lysis. 31  Streptococcus pneumoniae  Laboratory identification:  Under the microscope, it appears as encapsulated, lancet-shaped organism, occurring in pairs (hence the former name "diplococcus").  Samples obtained from a nasopharyngeal swab, blood, pus, sputum or spinal fluid can be cultured on blood agar. The colonies are -hemolytic. 32 Picornaviridae Common characteristics Genome (+)-sense, non-segmented ssRNA Shape Icosahedral Envelope X Replication Genomic RNAs serve as mRNAs & are infectious Coxsackievirus Important members Hepatitis A virus Poliovirus 33  Enteroviruses  Properties:  Individuals are infected with enteroviruses by ingestion of contaminated food or water.  Are stable at the low pH of the stomach, replicate in the GI tract & are excreted in the stool  viruses transmitted by the fecal-oral route.  Can cause CNS disease. 34  Enteroviruses  Replication:  Can replicate in a variety of tissues.  Bind to specific receptors on host cell surfaces.  Cells lacking these specific receptors are not susceptible to infection.  Can enter the bloodstream after replication & spread to various target organs. 35  Enteroviruses  Clinical significance:  Are the major recognizable cause of acute aseptic meningitis syndrome, which refers to any meningitis.  Treatment: symptomatic; the course of the illness is usually benign. 36  Enteroviruses  Laboratory identification:  Viruses can be isolated from the stool or from various target organs.  Evidence of infection can also be obtained by demonstration of a rise in antibody titer. 37 Enteroviruses Viral meningitis can usually be distinguished from bacterial meningitis:  The viral disease is milder.  There is an elevation of lymphocytes in the CSF, rather than the elevated neutrophils seen in bacterial meningitis.  [Glucose] in the CSF is not decreased.  Viral meningitis occurs mainly in the summer & fall, affecting both children & adults. 38 Herpesviruses Common characteristics Genome dsDNA Envelope + Initiated by a number of virus-coded enzymes & transcription Lytic state factors Latent state Follows primary infection, to be reactivated at a later time Epstein-Barr virus Herpes simplex virus Important members Human cytomegalovirus Human herpesvirus Varicella-zoster virus 39  Herpes Simplex Virus, types 1 & 2  Properties:  The only human herpesviruses that have a significant degree of nucleotide homology (≈ 50%).  Share many common features in replication, disease production & latency.  Transmitted by direct contact with virus-containing secretions or with lesions on mucosal or cutaneous surfaces.  HSV-1: most commonly found in lesions of the upper-body (ex: oropharyngeal region).  HSV-2: most commonly the cause of lesions below the waist. 40  Herpes Simplex Virus, types 1 & 2  Pathogenesis:  Lytic replication at the site of infection produces inflammation & giant cells.  Virus can infect & spread to neurons & establishes latency in sensory ganglia.  Reactivation can be induced by sun exposure, fever, trauma or stress. 41  Herpes Simplex Virus, types 1 & 2  Clinical significance:  If HSV infection spreads to the CNS, it can cause encephalitis which has a mortality rate estimated to be 70% if untreated.  Survivors are usually left with neurologic deficits.  HSV infections of the CNS account for up to 20% of encephalitis viral infections. 42  Herpes Simplex Virus, types 1 & 2  Laboratory identification:  Virus can be isolated from lesions & grown in cell culture.  HSV-1 & HSV-2 distinguished by type-specific monoclonal antibodies.  PCR of CSF used for diagnosis of herpes encephalitis. 43 Arboviruses Common characteristics Genome RNA Reservoirs Infected blood-sucking insects Togaviruses Flaviviruses Important members Bunyaviruses Reoviruses 44 Togaviruses Common characteristics Genome (+)-sense, non-segmented ssRNA Shape Icosahedral nucleocapsid Envelope + Replication Genomic RNAs serve as mRNAs & are infectious Alphavirus Genera Rubivirus 45 Togaviruses Laboratory Replication Pathogenesis Clinical significance identification Attachment to the Broad host range: replicate Persistent infection Isolation of virus cell surface. in organisms widely in arthropods. from CSF, blood or separated phylogenetically tissue. Internalization by (mosquitoes & humans). Acute infection in receptor-mediated humans: Rise in antibody endocytosis. Viremia follows inoculation - Acute encephalitis titer. by a mosquito. - Acute arthropathy Replication in the - Febrile illness with cytoplasm of the Scattering in various target a flu-like syndrome. infected cells. organs (CNS in the encephalitis viruses). 46 Flaviviruses Common characteristics Genome (+)-sense, ssRNA Shape Icosahedral nucleocapsid Envelope + Flavivirus Genera Hepatitis C virus Pestivirus 47 Flaviviruses Laboratory Replication Pathogenesis Clinical significance identification Attachment to the Transmitted to humans Association with Isolation of virus. cell surface. by the bite of an several ≠ clinical infected mosquito or syndromes: Demonstration of Entry via receptor- tick. - Encephalitis specific viral antigens. mediated - Hemorrhagic fever endocytosis. Viruses maintained in Rise in antibody titer. - Fever nature by replicating - Myalgia Accumulation of alternately in an virus particles in - Rash. arthropod vector & a vesicles & extrusion vertebrate host. when vesicles move to the cell surface. 48 Bunyaviruses Common characteristics Genome (-)-sense, ssRNA Shape Spherical Envelope + Bunyavirus Phlebovirus Genera Nairovirus Hantavirus 49 Bunyaviruses Laboratory Replication Pathogenesis Clinical significance identification Attachment to the cell Transmitted to Bunyavirus: Rise in antibody surface. humans by arthropod meningitis & titer. bite. encephalitis. Entry via receptor- mediated endocytosis. Exception: Hantavirus, Hantavirus: by rodents via hemorrhagic fever ± Maturation by budding aerosols formed from renal syndrome. into smooth-surfaced dried excretions. vesicles in or near the Golgi region of the infected cell. 50  Bunyaviruses  Transmission of California encephalitis virus: 51 Retroviruses Common characteristics Genome (+)-sense, linear ssRNA Shape Icosahedral Envelope + Human immunodeficiency viruses 1 & 2 Important members Human T-cell lymphotrophic viruses 1 & 2 52  HIV  Properties:  Member of the Lentiviruses.  Cause neurologic & immunologic disorders.  Does not have oncogenic properties. 53  HIV  Replication:  Presence of a reverse transcriptase: unusual enzyme, which converts a ssRNA viral genome into viral dsDNA.  2 identical copies of the (+)-sense ssRNA genome in the capsid  unlike other viruses, retroviruses are diploid. 54  HIV  Clinical significance: 55 Rabdoviruses Common characteristics Genome (-)-sense, non-segmented ssRNA Shape Bullet-shaped helical nucleocapsid Envelope + Replication Virion contains RNA-dependent RNA polymerase Important member Rabies virus 56  Rabies virus  Properties:  Reservoirs: a wide variety of wildlife (raccoons, skunks, squirrels, foxes & bats).  Important reservoirs in developing countries: domestic dogs & cats.  Humans are infected by the bite of an animal or via inhalation (droppings from infected bats). 57  Rabies virus  Pathogenesis: Local replication of Brain (via retrograde Inoculation transport within virus peripheral neurons) Infection of the lungs, kidney, adrenal Traveling (along Replication (primarily medulla & salivary autonomic nerves) in the gray matter) glands 58  Rabies virus  Pathogenesis: 59  Rabies virus  Clinical significance:  Clinical illness may begin with an abnormal sensation at the site of the bite.  It may progress to a fatal encephalitis, with neuronal degeneration of the brain & spinal cord.  Symptoms of the infection include: hallucinations, seizures, weakness, mental dysfunction, paralysis, coma & finally death.  Many patients show the classic rabid sign of hydrophobia, a painful inability to swallow liquids, leading to avoidance.  Once symptoms begin, death is inevitable. 60  Rabies virus  Laboratory identification:  Diagnosis rests on a history of exposure, signs & symptoms characteristic of rabies.  However, a reliable history of exposure is often not obtainable & the clinical presentation, especially in the initial stages, may not be characteristic.  Therefore, a clinical diagnosis may be difficult.  Postmortem, characteristic cytoplasmic inclusions (Negri bodies) may be seen in regions of the brain such as the hippocampus. 61  Cryptococcus neoformans  Properties:  Member of the opportunistic mycoses.  Has a characteristic polysaccharide capsule that surrounds the budding yeast cell.  Is especially abundant in soil containing bird droppings, although the birds are not infected.  Causes cryptococcosis. 62  Cryptococcus neoformans  Pathogenesis:  After being inhaled, cryptococci reach the alveoli, where production of the capsule is the prime determinant of virulence.  Pulmonary infection is associated with the appearance of a subpopulation of Titan cells = very large thick-walled forms, too large to be phagocytosed. 63  Cryptococcus neoformans  Pathogenesis:  Production of the capsule is induced in the tissue milieu through multiple environmental signals (iron, pH, CO2, glucose, nitrogen).  The capsule is antiphagocytic through complement depletion.  If phagocytosed by macrophages, Cryptococcus is able to survive & multiply by altering metabolic pathways.  This muting of the 1st lines of defense may allow the organisms to spread outside the lungs.  The affinity of C. neoformans for the CNS is striking: it crosses the blood–brain barrier inside macrophages (Trojan horse) or by transcytosis. 64  Cryptococcus neoformans  Pathogenesis: 65  Cryptococcus neoformans  Clinical significance:  Most common form of cryptococcosis is a mild, subclinical lung infection.  In immunocompromised patients: the infection often disseminates to the brain & meninges, with fatal consequences. 66  Cryptococcus neoformans  Laboratory identification:  Revealed in an India ink preparation.  A positive capsule stain on CSF can give a quick diagnosis of Cryptococcal meningitis (but false negatives are common). 67  Histoplasma capsulatum  Properties:  Exists in the environment as a mold with aerial hyphae.  Causes histoplasmosis. 68  Histoplasma capsulatum  Pathogenesis: Fungus Conidia (in soil) Lungs (when airborne) Macrophages (in which Yeast-like cells they multiply) 69  Histoplasma capsulatum  Clinical significance: Histoplasmosis  Its wide range clinical manifestations make it a particularly complex disease, often resembling tuberculosis.  Pulmonary infections may be acute but relatively benign & self-limiting, or chronic, progressive & fatal.  CNS manifestations occur in 10 to 20% of patients with disseminated histoplasmosis.  Additionally, histoplasmosis may be the cause of: o Cases of chronic meningitis in patients with no other evidence for dissemination o Cerebral or spinal cord mass lesions resembling neoplasms or abscesses o Encephalitis. 70  Histoplasma capsulatum  Laboratory identification:  Isolation & culture of the organism (slow process: 4 to 6 weeks).  Detection of exo-antigen in urine specimens. 71  Taenia solium  Properties:  Called Pork tapeworm.  Inhabits the human jejunum, where it may survive for decades. 72  Taenia solium  Life cycle: 73  Taenia solium  Clinical significance & laboratory identification:  Cysticercosis: seizures, headache & vomiting. Diagnosed by CT, MRI or biopsy.  Taeniasis: diarrhea (but mostly asymptomatic). Diagnosed by detection of proglottids in the stool. 74  Toxoplasma gondii  Properties:  An intracellular sporozoan, distributed worldwide.  Infects all vertebrate species, although the definitive host is the cat.  Humans can become infected by:  The accidental ingestion of oocysts present in cat feces  Eating raw or undercooked meat  Congenitally from an infected mother  From a blood transfusion. 75  Toxoplasma gondii  Pathogenesis: 2 kinds of Toxoplasma trophozoites found in human infections:  Rapidly growing tachyzoites (“tachy-” = rapid) that are seen in body fluids in early, acute infections. They directly destroy cells.  Slowly growing bradyzoites (“brady-” = slow) that are contained in cysts in muscle, brain tissue & the eye. Once released from ruptured tissue cysts, they cause local inflammation with blockage of blood vessels & necrosis. 76  Toxoplasma gondii  Clinical significance:  Infections of normal human hosts are common & usually asymptomatic.  They can be very severe in immunocompromised individuals, who may also suffer relapse of the infection.  Congenital infections can also be severe, resulting in stillbirths, brain lesions & hydrocephaly, & they are a major cause of blindness in newborns. 77  Toxoplasma gondii  Laboratory identification:  Serologic tests are now routinely used. 78  Trichinella spiralis  Properties:  Intestinal parasites of many flesh-eating mammals.  Causes trichinosis. 79  Trichinella spiralis  Replication: 1. In the host intestinal tissue, the male (1.5 mm) copulates with the female (3.5 mm) & dies. 2. Within 1 week, the female begins to discharge offspring that undergo intrauterine embryonation & are released as larvae. 3. The birthing continues for the next 4 to 16 weeks, resulting in the generation of ≈1500 larvae (6 by 100 μm each). 4. Larvae move: submucosa  vascular system  right side of the heart  pulmonary capillary bed  systemic circulation  distributed throughout the body. 5. Larvae penetrating tissue other than skeletal muscle disintegrate & die. 80  Trichinella spiralis  Pathogenesis:  Eating infected flesh spreads the disease.  Encysted larvae are freed by gastric digestion, penetrate the columnar epithelium of the intestine & mature just above the lamina propria. 81  Trichinella spiralis  Clinical significance:  Pathologic lesions of trichinosis are related to the presence of larvae in the striated muscle, heart & CNS.  Intense inflammation surrounds the involved area (neutrophils, lymphocytes & eosinophils).  Destruction of circulating larvae begins, production of new larvae is slowed & the expulsion of adult worms is accelerated.  Initial abdominal pain & diarrhea as adults penetrate (symptoms depend on number & extent of larval muscle invasion).  Severe complications include hemoptysis & heart failure. 82  Trichinella spiralis  Laboratory identification:  There are a number of valuable serologic tests.  Significant antibody titers are generally absent before the 3rd week of illness, but may then persist indefinitely.  Muscle biopsy during the 3rd week of illness often reveals coiled encysted larvae. 83  Trypanosoma  Properties:  Intestinal parasites of many flesh-eating mammals.  Cause trypanosomiasis, which refers to 2 chronic, eventually fatal, diseases, caused by several trypanosome species: 1. African sleeping sickness, occurs in East & West Africa, caused by the closely related flagellates: T. brucei gambiense or T. brucei rhodesiense. 2. American trypanosomiasis (= Chagas disease), occurs in Central & South America, caused by T. cruzi. 84  African sleeping sickness  Life cycle: 85  African sleeping sickness  Pathogenesis: Production of a Spread of the Tsetse fly injects primary lesion or organism to lymphoid parasites into humans chancre tissue Production of the Invasion of CNS, characteristic lethargy causing inflammation Reproduction & eventually of the brain & spinal extracellularly in the continuous sleep & cord, mediated by blood death released toxins 86  American trypanosomiasis  Life cycle: 87  American trypanosomiasis  Pathogenesis: Contamination of Granulomatous lesion Infection transmitted by conjunctiva or break in (1st symptom) at the site insect feces the skin of entry Potential long term Disease may go into Acute disease complications include remission but reappear characterized by fever cardiomyopathy & as digestive system & hepatosplenomegaly megacolon problems 88  Trypanosoma  Clinical significance:  African sleeping sickness: highly lethal meningoencephalitis.  American trypanosomiasis: acute febrile illness in children & chronic heart or GI malady in adults. 89  Trypanosoma  Laboratory identification:  Diagnosis is made primarily by detection of motile trypanosomes in Giemsa stained smears of body fluids.  Highly specific serologic tests are also available for diagnostic confirmation. 90