CNS Infections Flashcards

Question

Hand, Foot, and Mouth (A16) Disease

Answer 1

* Most common in **children under 5** * Fever, ST, **oral lesions** that start as papules and become blisters * **Palms and soles** involved

Answer 2

Enteric Cytopathic Human Orphan Viruses Types 1-34 * Leading cause of **viral meningitis** * Typically associated with a **petechial** **rash** * Disease is usually **self-limiting** * Severity based on viral serotype, dose, pt status and age

Answer 3

* **Inflammation of the brain parenchyma** _with or without meningeal irritation_ * **Meningoencephalitis**: Inflammation of the meninges and brain parenchyma * Usually has a viral etiology * Characterized by headache, fever, muscle aches/weakness, **confusion, seizures, paralysis, LOC** * Agents: HSV-1 and 2, Arboviruses, Naegleria, Rabies virus, Measles, Rubella

Answer 4

* **Severe, devastating encephalomyelitis** * Disease occurs throughout the year and in persons of all age groups * 50% due to primary infection * 50% due to recurrent infection * Dx w/ **PCR** of viral DNA from CSF * **Acyclovir** reduces morbidity and mortality * _Histology: 3 M's_ * **Multinucleation** * **Margination** of chromatin to the periphery of the nucleus * **Molding** of the nuclei together

Answer 5

* **HSV-1** in _children and adults_ * Virus in trigeminal ganglion → temporal lobe via **neurogenic pathways** * **Temporal lobe and base of the brain** * **Necrosis** and **hemorrhage** * Antiviral agents may be helpful in acute therapy

Answer 6

* **HSV-2** in _neonates_ * Transmitted in **birth canal** of infected mother * C-section reduces risk * **CNS and systemic disease** ⇒ High morbidity and mortality

Answer 7

* Rare in North America * **Rapidly fatal necrotizing encephalitis** with ***Naegleria* species** (most common) * **Chronic granulomatous meningoencephalitis** with **Acanthamoeba**

Answer 8

* **Protozoan** **parasite** * 3 developmental stages: **cyst, flagellate and amoeboid (trophozoite) forms** * Cyst form occurs under unfavorable conditions * Other forms are **free living and thrive in warm freshwater**

Answer 9

* 3 developmental stages: **cyst, flagellate and amoeboid (trophozoite) forms** * Flagellate and trophozoites are **free living and thrive in warm freshwater** * Only trophozoites are infectious

Answer 10

* Lives in very warm **freshwater lakes** mostly in **southern states**, **hot springs** and **thermally polluted waters** (powerplant runoff) * Found in **sediment** & **disturbed by water activity** * **CNS entry through nose → cribriform plate and emissary veins** * **Travels along the olfactory nerve to the brain** * Infections occur during the summer months * 33 documented infections since 1996 with only 3 survivors

Answer 11

* Early sx may include **nasal congestion and loss of sense of smell** * Symptoms of **severe hemorrhagic, destructive** **meningo-panencephalitis** occur _1 - 14 days_ after contact * Includes **headache, fever, nausea, vomiting and stiff neck** * Progress to **seizures, loss of motor control and cognitive function** * Infection is fulminant and progresses to **death within 3-6 days** * 95% mortality

Answer 12

* **ID organisms in brain on autopsy** * A few cases have been dx early by the ID of trophozoites in CSF

Answer 13

* Treatment: * Only a few cases successfully treated with **Amphotericin B** * Prevention: * Adequate chlorination of swimming water * Avoid water related activities during period of high temp * Hold the nose shut during water related activities in high-risk areas

Answer 14

* Caused by ***Taenia solium*** (pork tapeworm) * Common in developing world * Man is the _intermediate host_ for *T. solium* * _Transmission and Pathogenesis:_ * **Fecal contamination of drinking water with eggs** * Larvae hatch and penetrate gut * Disseminate in **blood** * Cysts (cysticerci) develop in any organ * Prefer **brain, muscles, skin and heart** * In CNS become small, gliotic foci * Usually not lethal, but often **neurologically symptomatic** and can cause ↑ ICP * **Seizure** is common presentation * Treatable with anti-helminthics

Answer 15

* **Gram ⊖**, **obligate aerobe spirochete** * Long and thin with **hooks at one or both ends** * Has periplasmic flagella ⇒ **highly motile** * Classified on the _basis of specific antigens_ into 150 different strains called **serovars** * Easiest spirochete to grow ⇒ cultured on **serum enriched media** * Leptospirosis is usually a **mild infection in both man and other animals** * Common in Hawaii

Answer 16

* **Contact with water, food or soil contaminated with urine of infected animals** * Entry usually via **ingestion or abrasions** * Blood → kidney → urinary excretion

Answer 17

* Disease ranges from **subclinical** to **mild flu-like symptoms**, **meningitis** or **severe systemic disease** * Severity related to **serovar of infecting strain** * About 10% of individuals develop a highly fatal form known as **Weil's disease** * Characterized by **jaundice, liver and kidney failure, vasculitis and myocarditis**

Answer 18

_Serology_, by **microscopic agglutination** **Cultures** of blood, spinal fluid and urine

Answer 19

Due to **bactericidal antibody** and is **serovar specific** Avoid exposure to contaminated water/animals

Answer 20

Arthropod-borne virus ⇒ any virus transmitted by arthropod vectors * Infects vertebrates and invertebrates * Transmitted via **bite of infected arthropod (mosquito)** * Initiate _persistent productive infection_ in salivary glands of **small mammals, birds, and/or arthropods** * _Humans_ are usually **dead-end hosts** * Spring, Summer, early Fall * **Aseptic meningitis** to **severe encephalitis** that can cause serious morbidity and high mortality * _CSF:_ * Few lymphocytes * ↑ Protein * Normal glucose * Neuronal necrosis ⇒ **neuronophagia**

Answer 21

* **Togaviruses (Alphaviruses)**: enveloped, ⊕-sense ssRNA * **Flaviviruses**: enveloped, ⊕-sense ssRNA, smaller than alphaviruses * **Bunyaviruses**: Enveloped, helical nucleocapsid, 3 segments of ⊖-sense ssRNA

Answer 22

* Disease during **summer months** and **rainy seasons** * Viruses **multiply in vertebrate and blood sucking insect hosts** * **Extrinsic incubation period** ⇒ time needed for virus to multiply in arthropod and achieve a concentration sufficient to infect and cause disease in humans * Some insects maintain the virus in nature by **transovarial transmission** * **Humans usu. dead-end host** ⇒ insufficient viremia * Exceptions include **urban yellow fever and dengue** * Humans can serve as reservoirs * Longer persistence of virus in blood and/or sequestration in the organs (West Nile infections) * Implications for blood banking and organ transplantation

Answer 23

* Replicates in **endothelial cells, monocytes, and MΦ** * Good inducers of **Type I Interferons** * Flu-like sx initially * Spread to CNS via **viremia** * IgG may block * Delayed Ab response results in CNS disease

Answer 24

_Range of diseases:_ * Many infections are **asymptomatic** * **Flu-like syndrome** * Fever with myalgias, arthralgias, and non-hemorrhagic rash * **Encephalitis** * Fever, HA, AMS, seizures, coma * **Hemorrhagic Fever ⇒** Dengue

Answer 25

* **Flavivirus** * Originated in Eastern Africa, Middle East * _Reservoir_: **Wild birds** * _Vector_: **Mosquito**

Answer 26

* **Asymptomatic** (80%) * **West Nile Fever** (20%) * Flu-like syndrome * **West Nile meningitis or encephalitis** (0.5%) * Neuro-invasive * May include muscle weakness and/or paralysis

Answer 27

* First seen in US in 1999 * **Highest incidence in AZ, NY, TX** * Outbreaks usu. **preceded by infection in the bird population** * _Risk factors:_ * Immunocompromise * Age – very old or very young * Pregnancy * _Median age_ * Symptomatic disease 47 y/o * Neuro-invasive disease \> 75 y/o

Answer 28

* **Mosquito bites** * **Transfusion and transplanted organ** * Seen in early 2,000s * Red cross started screening blood in 2003 * **Intra-uterine / breastfeeding** Suggests **longer viremia** than other encephalitis viruses and/or **sequestration in tissues** of healthy individuals

Answer 29

* **Spraying** when mosquitos breed * **Eliminating breeding sites** (stagnant water) * Caution susceptible individuals to wear **protective clothing or stay indoors** during mosquito feeding times

Answer 30

* **Flavivirus family** * Enveloped, ⊕-sense ssRNA, smaller than alphaviruses * Replicates in the cytoplasm * Genome serves as mRNA * Translation is the first step in replication * _Reservoirs_: **monkeys and humans** * _Vector_: **urban mosquito (*Aedes aegypti)*** * **Four serotypes**

Answer 31

* **Tropical and subtropical areas** * High density viremic population for transmission * May be asymptomatic * \> 50% of world’s population at risk of infection * 50-100 million cases of dengue fever each year

Answer 32

**“Breakbone fever”** 1° infection w/ Dengue virus * _Clinical manifestations:_ * **High fever**, chills, malaise * Headache, **retro-orbital pain** * **Severe lumbosacral back and bone pain, myalgias** * **Rash** is frequently present * Runs its course in **5-7 days** * **Usually resolves without complications**

Answer 33

* Replicates 1° in **vascular endothelium and monocytes or** **MΦ** * Induces release of large quantities of **cytokines** * **Viremia** ⇒ systemic spread ⇒ viral amplification * **Neutralizing Ab** ⇒ resolution of infection * _Subsequent infection_ w/ different serotype can lead to **Dengue Hemorrhagic Fever (DHF)** or **Dengue Shock Syndrome (DSS)** * DSS or DHF may occur _even if 1^st dengue infection asymptomatic_

Answer 34

* 1° infection w/ any serotype ⇒ virus specific Ab ⇒ life-long immunity to that serotype * Ab acts as “**enhancing antibody**” to other serotypes * _Infection w/ a different serotype_ ⇒ **Dengue Hemorrhagic Fever (DHF)** or **Dengue Shock Syndrome (DSS)** * **Formation of immune complexes** (virus-Ab) ⇒ internalized via Fc receptors into MΦ * More efficient infection * Greater replication of the virus * ↑ production of MΦ cytokines * _MΦ processed virus interacts with T-cells_ ⇒ **hypersensitivity rxn @ endothelial surface** * Circulating immune complexes ⇒ ± complement activation ⇒ **release of vasoactive amines** * ↑ vascular permeability, perivascular edema, and mononuclear infiltration ⇒ **effusions in the pleura and other cavities** * ↓ Platelet production ⇒ ↓ clotting factors ⇒ **± hemorrhage from respiratory & GI tracts**

Answer 35

* **No vaccine** * Attenuated tetravalent vaccine in clinical trials * Mosquitos feed all day w/ peak in early morning and late afternoon * **Use protective clothing and insect repellant**

Answer 36

* _Includes:_ * **Arenaviruses** * Lassa virus * Machupo virus * Junin virus * **Filovirus** * Marburg virus * Ebola virus * **Hantavirus** * Hantaan virus * Sin Nombre virus * All enveloped RNA viruses * **Animal or insect reservoir** * Monkeys, rodents, bats * **Humans are not the natural host** * Except for Dengue * Geographically restricted to where reservoir lives

Answer 37

* **Initial transmission** * Occurs when activities of reservoir, host, or vector overlap * Transmission mech. to humans unknown * Ex. contact w/ bush meat – Marburg * **Ongoing transmission** * Once infection occurs in humans, **highly transmissible by body fluids to others** * Occurs in outbreak form * Ex. Ebola, Marburg, Lassa

Answer 38

* **Initial Syndrome** * Abrupt onset of **flu-like illness** * Fever, fatigue, malaise, headache, joint and muscle aches * Progresses to either conditions below * **Pulmonary shock-like syndrome** * Pulmonary edema * Respiratory failure * Death * **Hemorrhagic syndrome** * Coagulopathy * Petechial hemorrhage * Bleeding from gums, eyes, ears, and GI tract * DIC, organ failure, death

Answer 39

Supportive therapy only High mortality rates

Answer 40

* **Hantaan virus** * **Causes hemorrhagic fever or pulmonary shock syndrome** * **Outbreaks common in US national parks** * Hikers, campers, seasonal cabin dwellers, occupational risks * Transmission via contact w/ aerosolized mouse feces, urine * **Sin Nombre Virus** * **Causes pulmonary shock syndrome** * Outbreak in Four Corners region in 1993 * **Endemic in Eastern Asia** (China, Russia, and Korea) * Deer mouse vector * Transmission by breathing aerosols containing virus from contaminated urine * Outbreaks coincide with high rainfall, increased food and rodent population

Answer 41

* **Hantavirus Pulmonary Syndrome (HPS)** * Flu-like syndrome for 2-3 days * Dry cough, malaise, HA, N/V, SOB * Progresses to ARDS, kidney failure * Mortality 35% * **Hemorrhagic Fever with Renal Syndrome (HFRS)** * Eastern Asia (China, Russia, and Korea) * Intense HA, nausea, fever, chills, back and abd pain * Low BP, acute shock, vascular leakage * AKI ⇒ severe fluid overload * Mortality up to 15% depending on strain

Answer 42

* _Diagnosis:_ * Serology, immunohistochemistry, PCR * _Treatment:_ * Largely supportive * Intubation and oxygen therapy for HPS * IV ribavirin for HFRS (early)

Answer 43

* Hemorrhagic virus * Endemic in Africa and parts of South America * **Enveloped, ambisense RNA** * Includes **Lassa, Machupo, Junin** * _Reservoir_: persistent infection in **rodents** * Shedding of virus in saliva, urine, and feces

Answer 44

* Hemorrhagic virus * Endemic in Africa and parts of South America * **Enveloped ⊖-sense RNA** * Includes **Marburg and Ebola** (50-90% mortality) * _Reservoir_: **monkeys, bats**

Answer 45

**Severe encephalitis of midbrain and medulla** * Bite of infected animal: racoons, dogs, bats * **Neurotrophic transmission** * **Negri bodies** are pathognomonic * **Extraordinary CNS excitability** (sensory & motor) * Pharyngeal muscle contraction ⇒ **hydrophobia** (do not drink water) * **Flaccid paralysis, mania/stupor, coma** * Pre and post-exposure vaccination is effective

Answer 46

* Rhabdoviridae family of RNA viruses * Infect many mammals including humans * Bullet shaped w/ **glycoprotein coat** surrounding **matrix protein** * **Helical ribonucleoprotein core** * **Unsegmented** **⊖-sense** **ssRNA** * Contains an **RNA dependent RNA polymerase** * Replicates entirely in the cytoplasm * _Excess nucleocapsid_ material accumulates in cytoplasm of infected cells ⇒ forms characteristic inclusions known as **Negri bodies**

Answer 47

* _Incubation_**: 4 weeks to \> 1 year** * Duration depends on bite site (shorter w/ bites of face and head), age, concentration of virus, and host immune status * **Enters muscle @ bite site & replicates** * No sx during incubation period * **Virus infects the peripheral nerves** ⇒ _prodromal phase_ * Fever, nausea, vomiting, headache, lethargy * **Retrograde axonal transport** **→** **DRG of spinal cord** * **Travels up the CNS to the brain** ⇒ _neurological phase_ * Affects **hippocampus, brainstem, and cerebellum** * CNS manifestations including **depression, anxiety, hallucinations, hydrophobia, paralysis, delirium and seizures** * _Gross brain_: may see **mild congestion w/ perivascular infiltration or cuffing**, no tissue necrosis * From CNS, disseminates to the body including **skin, salivary glands, cornea, adrenals, and kidneys** * **Replication takes place in the brain** and probably also in **salivary glands** * Stage progresses to **coma and death within 1 to 3 weeks** * Death usually occurs from pulmonary or cardiac complications

Answer 48

* _Antemortem diagnosis_ * **Fluorescent microscopy of skin biopsy of the nape of the neck** * Isolation of virus from saliva * Ab in CSF or serum * _Postmortem diagnosis_ * **Negri bodies in the brain (70-90%)**

Answer 49

_Treatment consists of three phases:_ 1. **Local wound management** * Thorough flushing and disinfection of wound essential * Assess need for tetanus prophylaxis 2. **Passive immunization** * Given **rabies immune globulin (RIG)** within 24 hours * Goal to prevent virus from entering neural tissue * Little value once sx begin 3. **Vaccination** * 3 commercially available **inactivated virus** vaccines * 5 doses given IM within 1 month * **1^st dose of vaccine @ the same time as passive therapy but at separate sites**

Answer 50

* **Pre-exposure vaccination** * For individuals in high-risk groups * Veterinarians, animal handlers, rabies virus lab workers and spelunkers * Boosters may be advised for those with continuing risk * **Key prevention strategies include:** * Vaccination of domestic dogs, cats and ferrets * Avoid contact with wildlife and strays * Seal chimneys and opening into houses to prevent den building * Wear gloves or use a shovel to dispose of a bat once you think you’ve killed it

Answer 51

* _Some combination of:_ * **Headache** * **Fever** * **Nuchal rigidity** (stiffness of the neck on passive forward flexion) * **Nausea** * **Lethargy** * **Reduced consciousness** * **Seizures** (particularly in children) * Paralysis and motor deficits more associated with encephalitis * Many of the signs and sx of encephalitis overlap with those of meningitis

Answer 52

_Vary with patient’s age:_ * **Neonates**: E. coli and group B Streptococci * **Infants**: S. pneumoniae * Immunization (1987) marked decrease in H. influenzae * **Adolescents and young adults**: Neisseria meningitidis * **Adults**: S. pneumoniae * **Older Adults / Immunocompromised**: Listeria monocytogenes

Answer 53

* Group B Streptococci * Escherichia coli * Listeria monocytogenes

Answer 54

***Streptococcus agalactiae*** * Causes 10% of meningitis cases overall * **# 1 cause of neonatal sepsis and meningitis** * ~10k cases/year of GBS, ~300 deaths/year in the USA, 1-3 cases/1k births * Important in neonates but increasing in \> 50 y/o * **High mortality**: up to 30% of cases die even w/ treatment

Answer 55

* **Gram ⊕ cocci** in chains * **β-hemolytic** * Bacitracin resistant * CAMP test ⊕ Differentiated from Group A β-hemolytic strep ⇒ Bacitracin sensitive & CAMP ⊖

Answer 56

* Normal intestinal flora and **normal vaginal flora (10-30% of women)** * Neonates acquire during **passage through birth canal** * Direct contact after birth * **Entry through respiratory system, skin, GI tract** * Risk factors for disseminated GBS infection: * Lack of response to polysacc Ag * Underdeveloped neonatal immune system

Answer 57

* 60% of infants born to colonized women become colonized * Premature delivery * Prolonged membrane rupture (\>18 hrs) * Intrapartum fever of mom (38°C) * Previous neonate w/ GBS * Detection of GBS in urine

Answer 58

_High risk groups:_ * African Americans * Diabetics * Sexually active * Multiple partners

Answer 59

* **Polysaccharide capsule** * 11 serotypes * Ia, **III**, and V most often ass. w/ disease * Rich in sialic acid

Answer 60

Presents w/ **fever, lethargy, difficulty feeding, irritability, respiratory distress, hypotension, cyanosis.** * **Entry through respiratory system, skin, GI tract** * Normal sequence of events: **Pneumonia** **→** **Bacteremia** **→** **Meningitis** * Starts w/ mucosal infection (PNA) * Encapsulated organisms can easily move from blood into CNS * **Mortality ~ 5%** * Depends on birthweight: \> 1500 g = 14% mortality, \< 1500 g = 65% mortality (1 kg = 2.2 lbs) * **Neurologic sequalae in 15-30% of survivors**

Answer 61

* **Early-onset infections** * **Serotypes I, II, III** * **Sx during first 5 days of life** * Infection acquired during birth * ↑ Risk w/ premature delivery & prolonged rupture of membranes \> 12 hrs * **Late-onset infection** * **Serotype III** * Seen in full term infants * Presents at **7 days - 3 months old** * Direct contact transmission: nursery, mother * ↑ survival, ↔︎ neurologic sequalae

Answer 62

* _Diagnosis_: * **Cultures of blood or CSF** * _Treatment_: * **Penicillin or Ampicillin IV** * Sometimes in combo w/ **aminoglycosides** * _Prevention_: * Screen of pregnant women @ 35-36 weeks gestation * Intrapartum prophylaxis of culture ⊕ women ↓ transmission * Colonized or high risk women * IV Abx during labor * High risk newborns * IV Abx for 48 hrs after birth

Answer 63

* **#2 cause of neonatal sepsis (40%) and meningitis (75%)** * Enterobacter, Proteus and Klebsiella can also cause neonatal sepsis * Neonates (\< 1 m/o) acquire E. coli during **passage through birth canal** * Transmission from nursery personnel also seen * Virulence ⇒ **anti-phagocytic K1 capsular polysaccharide** * Rich in sialic acid * Neurotropic and assists in adherence to meninges * Very resistant to phagocytosis

Answer 64

* **Uncommon cause meningitis & sepsis (10% overall)** * **Gram ⊕ rods** * Elderly and pts with impaired T-cell immunity * Transmission * Fetus via **placenta** * Neonate via **birth canal** * **Ingestion** ⇒ outbreaks * Young children * Elderly * Immunocompromised of all ages

Answer 65

* Streptococcus pneumoniae * Haemophilus influenzae Type B * Neisseria meningiditis

Answer 66

***Streptococcus pneumoniae*** * Causes **50%** of septic meningitis cases * **#1 cause of meningitis in children \< 6 y/o** after neonatal period and **\> 20 y/o** * Can cause meningitis in all age groups * Children * Nasopharyngitis and otitis media with hematogenous spread * Elderly (very old) * PNA with hematogenous spread * Conjugate vaccine has reduced incidence * 20% mortality * Frequent cause of severe neurologic sequalae including **cortical deficits and deafness** (25-50%)

Answer 67

* Transmission: * **Usually endogenous** * Exogenous via **respiratory secretions** * Accompanied by pre-disposing factors * Epidemiology: * Infects humans, no reservoir * **20-40% are carriers in NP** * **Incidence greatest \< 6 y/o and \> 60 y/o** * 1 mil deaths worldwide

Answer 68

\> 80 serotypes based on **capsular polysaccaride**

Answer 69

* **Polysaccharide capsule** ⇒ major factor * Anti-phagocytic * Strains w/ large capsules more virulent * Loss ⇒ avirulent * **IgA protease** * Aids establishment of infection * **Pneumolysin** * Toxin w/ pore-forming action * Injures cilia and endothelial cells ⇒ aids spread

Answer 70

* Starts w/ mucosal infection (PNA, otitis media) * Spreads via blood to CNS * Massive inflammatory response, mostly PMNs * Edema and accumulation of pus

Answer 71

* **Smear** ⇒ gram ⊕ cocci * **Culture** ⇒ blood agar or blood culture * **Optochin sensitive** * Detection of capsular Ag * **Latex agglutination test** * **_Quellung reaction_** * Ab to organisms in pure culture or clinical material * Causes capsule to swell * Can be used for typing

Answer 72

50% are PCN resistant **Fluoroquinolones** or **Vancomycin** for serious disease.

Answer 73

* **1st gen vaccine (Pneumovax 23)** * Capsular polysacc. from 23 most common serotypes * Rec. for high risk pts * **Conjugate vaccine (Prevnar 13)** * 13 invasive serotypes polysacc. + CRM proteins * Given to infants as part of routine vaccinations

Answer 74

* **Causes \< 10% of meningitis cases overall** * Formerly important pathogen in children * Nasopharyngeal infections with hematogenous spread * Less common since immunization (HIb)

Answer 75

* **Meningitis only caused by HiB** * Usually follows URT infection * **Vaccine preventable** * Unimmunized child \< 2 y/o high risk * **3-6% mortality** * Sequalae frequent ⇒ **20% w/ permanent hearing loss**

Answer 76

* Small, **gram** **⊖** **rods** (cocco-bacillus) * Complex nutritional requirements * **X factor** ⇒ hematin * **V factor** ⇒ NAD or NADP * Grows well on chocolate agar * Small satellite colonies grow around colonies of S. aureus or other factor V excreting organisms ⇒ **satellite phenomenon** * **Most invasive strain** ⇒ causes 90% of all H. influenzae infections * Virulence due to unique **polyribose-ribitol phosphate (PRP) capsule**

Answer 77

* **Fastidious** * Specimen from NP swab, pus, blood, or CSF for smears and culture * **Grows on chocolate agar or BAP with X factor (hematin/hemin) and V factor (NAD)** * PRP capsular Ag of HiB released into body fluids * Antigen detection methods ⇒ **latex agglutination**

Answer 78

* **Passive protection by maternal Ab** * No episodes until after 6 m/o * **Opsonizing anti-capsular Ab** * Capsule-type specific * Enhance phagocytosis by PMNs * Bacteriolytic in presence of complement * Active acquired Ab gradually increases up to ~ 10 y/o

Answer 79

* **Ampicillin for 5-10 days** * **Some are beta-lactamase producers** * ~ 25% of HiB * **Newer cephalosporins are drugs of choice** * Ceftriaxone, cefotaxime

Answer 80

* Causes **25%** of meningitis cases overall * **Children \< 5 y/o, adolescents and young adults** * **Most common cause of epidemic meningitis** * Airborne transmission * Vaccination available (military and most colleges require it) * **Pyogenic gram-****⊖****diplococci** * **13 serogroups** based on _capsular carbohydrate composition_

Answer 81

* **Respiratory droplet transmission** * Prolonged close contact ↑ risk * Humans are the only natural host * **Common** **in children (6 mo – 2 yrs) and adolescents** * Transient colonization of nasopharynx (1-40%) * 5% of population chronic carriers (up to 35% of military recruits) * **Epidemic outbreaks** * USA ⇒ Group B * Rest of the world ⇒ Group C * Usually seen in Winter and Spring * **Bimodal distribution** * Maternal Ab gives protection (6-9 m/o) * **Disease peak in children (\< 1 y/o)** * **2^nd peak in adolescents and young adults (15-25 y/o)**

Answer 82

* Age * Winter / dry season * Overcrowding * Certain social behaviors * Passive exposure to cigarette smoke

Answer 83

* **Polysaccharide capsule** ⇒ resists phagocytosis * Linked to bacterial protection and invasion * Polymers of sialic acid * Most strains have **pili** **(outer membrane proteins)** * Attach to CD46 * Facilitates invasion into mucosal epithelial cells * Non-piliated mutants less pathogenic * **Endotoxin/LOS (lipo-oligosaccharide)** ⇒ same activity as LPS * Proinflammatory mediators * Fever, shock, alternate complement pathway activation * **IgA protease**

Answer 84

* **Nasopharyngitis** * Most infections mild or inapparent * Frequently transmitted by droplets, coughing and sneezing * **Meningococcemia** * Septicemia occurs w/ or w/o meningitis * Thrombosis of small blood vessels * Produces **metastatic lesions** → skin, joints, eyes, lungs, etc. * Skin involvement ⇒ **petechial rash,** may become confluent and produce purpura * 40% mortality * **Meningitis** * Inflammation and pyogenic infection of meninges * Abrupt onset HA, fever, stiff neck, ± N/V * ± **Petechial rash** and **metastatic lesions** in other organs * Does not develop following every case of nasopharyngitis or meningococcemia * 9-12% mortality w/ abx * **Fulminating meningitis** * Severe meningitis w/ sudden onset of sx * Characterized by presence of a large number of organisms in the blood stream and meninges * **± DIC** **and gram-****⊖****shock** * **“Waterhouse-Friderichsen syndrome”** * Commonly associated w/ meningococci * Adrenal gland bleeding and destruction

Answer 85

* Most commonly caused by N. meningitidis * Overwhelming meningococcemia leads to **massive hemorrhage in the adrenal glands** * Characterized by **low BP, shock, DIC, widespread purpura, and rapidly developing adrenocortical insufficiency**

Answer 86

* Need **Ab response to the capsule** * Carriers develop protective response (anti-capsulate Ab) over time * **Complement deficiency of terminal components** (C5-C8) predisposes to disseminated disease

Answer 87

* **Gram stain** ⇒ presumptive dx * Grow on chocolate agar, **Thayer Martin Agar** * **Latex agglutination** * Direct detection of capsular polysaccharides * **Low sensitivity for serogroup B** ⇒ helpful if ⊕, does not r/o if ⊖ * **PCR of CSF** * If abx have been used and to type strains * **Biochemical tests** * All *Neisseria* are **Oxidase** **⊕** * *N. gonorrhoeae* is Glucose ⊕ only * *N. meningitidis* is **Glucose** **⊕,** **Maltose** **⊕**

Answer 88

* _Treatment_ * **Penicillin G** (no known PCN resistance) * **Ceftriaxone** or **chloramphenicol** if febrile * Ceftriaxone will also cover other causes of bacterial meningitis (e.g. GBS) * _Prophylaxis for close contacts_ (e.g. family members) * **Oral Rifampin** ⇒ reaches high concentrations in oral secretions * _Prevention_ * Vaccines available for less prevalent serogroups * **Serogroups A, C, Y, W-135** ⇒ ↓ carrier rate * Conjugate licensed for US adolescents * **New Group B vaccine** * Poorly immunogenic capsule * For 16-23 y/o, high risk, or outbreak control

Answer 89

* _Organisms:_ **Streptococci or Staphylococci** * _Sources:_ * Direct implantation * Local extension (mastoiditis, sinusitis) * Hematogenous (heart, lungs, bone, teeth) * _Predisposition:_ * Infective endocarditis * Right to left cardiac shunts (bypasses lungs) * Chronic pulmonary sepsis (bronchiectasis) * _Location_: **Frontal lobe \> parietal lobe \> cerebellum** * _Clinical_: * **Progressive focal deficits** * **↑ ICP, WBCs and protein** * **Normal glucose** * _Causes death by:_ * ↑ ICP ⇒ **herniation** * Abscess rupture ⇒ **ventriculitis, meningitis, venous sinus thrombosis**

Answer 90

* Tuberculosis * Neurosyphilis * Neuroborreliosis

Answer 91

**Chronic Meningoencephalitis** * Part of diffuse active disease vs “isolated” seeding from undiagnosed infection (often PNA) * Most common pattern is **diffuse** **meningoencephalitis** * May spread via CSF to the choroid plexus and ependymal surface * _Clinical manifestations_: **headache, malaise, mental confusion, and vomiting** * _Gross:_ * Subarachnoid space w/ **gelatinous or fibrinous exudate** * Characteristically involves the **base of the brain**, **effacing the cisterns** and **encasing cranial nerves** * _Micro:_ * Mixed inflammatory infiltrates * **Well-formed granulomas** with **caseous necrosis** and **giant cells** * Organisms can be seen with **acid-fast stains** * _CSF:_ * Moderately increased cellularity (lymphocytes, PMNs) * **Protein elevated, often markedly** * **Glucose moderately reduced or normal** * Bacteria may be cultured from the CSF but typically not seen in cytology specimens

Answer 92

* **Arachnoid fibrosis** ⇒ hydrocephalus * **Obliterative endarteritis (Heubner’s Arteritis)** ⇒ arterial occlusion and infarction of underlying brain * **Tuberculoma** * **Pott Disease**

Answer 93

* **Severe proliferating endarteritis** (inflammation of the intima or inner lining of an artery) * Results in occlusion of artery lumen * Seen in both **TB and Syphilis**

Answer 94

* Inflammation may become **localized** and form a **mass-like lesion** * Causes mass effect * **Caseating granulomas** * May be calcified

Answer 95

**“Vertebral Tuberculosis”** * Rare * Neurologic complications from **collapse of vertebral bodie**s ⇒ **spinal cord compression** * May form **soft tissue abscesses** adjacent to involved vertebrae

Answer 96

* Caused by **Treponema palladium** (gram ⊖ spirochete) * **CNS involvement** in ~10% of untreated cases * Usually **3-10 years** after primary infection * _Patterns of CNS involvement:_ * **Meningovascular Neurosyphilis** * **Paretic Neurosyphilis** * **Tabes dorsalis** * _Transmission_: **sexual contact**, **congenital** (crosses the placenta), **contact with a primary lesion**

Answer 97

* Typically involves **base of brain, convexities, spinal cord** * _Microscopic_: * **Dense lymphoplasmacytic inflammation** * _CSF:_ * **WBC: variable lymphocytes and plasma cells** * **↑** **Protein** * **Glucose normal to low** * Organisms generally not seen in cytology specimens * VDRL (Venereal Disease Research Laboratory): ⊕

Answer 98

**Chronic meningitis** due to T. palladium * Typically involves the **base of the brain** and more variably the **cerebral convexities** and **spinal leptomeninges** * _Complications:_ * **Obliterative endarteritis (Heubner arteritis)** * Accompanied by **distinctive perivascular inflammatory reaction** rich in plasma cells and lymphocytes * **Cerebral Gummas** * ± Plasma cell-rich mass lesions in meninges → parenchyma * Typically seen in bone and skin

Answer 99

**Invasion of the brain** by *T. pallidum* * Clinically _insidious_ but _progressive_ **cognitive impairment** * Mood alterations (including delusions of grandeur) * Terminate in severe dementia (general paresis of the insane) * **Parenchymal damage** of the cerebral cortex most common in _frontal lobe_ but also other areas * Micro: * **Loss of neurons** * **Proliferation of microglia (rod cells)** * **Gliosis** * **Iron deposits** * Spirochetes may be demonstrated in tissue sections

Answer 100

**Damage to sensory axons in the dorsal roots** by *T. pallidum* * _Clinical manifestations:_ * Impaired joint position sense and ataxia (**locomotor ataxia**) * **Loss of pain sensation** ⇒ joint damage (**Charcot joints)** * Characteristic “**lightning pains**” * **Absence of DTRs** * Other sensory disturbances * _Microscopic:_ * **Loss of axons and myelin in dorsal roots** * **Pallor and atrophy in the dorsal columns**

Answer 101

* **Lyme Disease** sequelae * Caused by **Borrelia burgdorferi** (gram ⊖ spirochete) * Transmitted by Ixodes tick * _Symptoms variable:_ * **Facial nerve palsies** * **Other polyneuropathies** * **Encephalopathy**

Answer 102

* Primarily in **immunocompromised** individuals * CNS typically involved following widespread **hematogenous dissemination** * Can be **local extension** (DM, Neutropenia) * Most frequent pathogens: * ***Candida albicans*** * **Mucor species** * ***Aspergillus fumigatus*** * ***Cryptococcus neoformans*** * In endemic areas - ***Histoplasma*, *Coccidioides*, and *Blastomyces*** * _Three main forms of injury:_ * **Chronic meningitis** * **Vasculitis** – (Aspergillus & Mucor—sometimes others) * **Parenchymal invasion**

Answer 103

* Common opportunistic infection in **AIDS** * May be **fulminant and fatal** in as little as 2 weeks or **indolent, evolving over months or years** * Clinical: **Few meningeal symptoms** * CSF may contain **few cells** but usually has a **high concentration of protein** * **Polysaccharide capsule** (usually) * Examination of the brain shows **gelatinous material** within the _subarachnoid space_ and **small cysts** within the _parenchyma_ (“**soap bubbles**”) * _Diagnosis in CSF:_ * **Cryptococcal antigen** * Cytology * India ink stain [Historical] * Treatable with antifungal drugs

Answer 104

Protozoal CNS Infection * _Opportunistic infection_ ⇒ **HIV** * **Subacute**, evolving during a 1- or 2-week period * May be both **focal** **and diffuse** * _Microscopic:_ **free tachyzoites and encysted bradyzoites** at the _periphery of the necrotic foci_ * _Vessels near lesions_ may show **marked intimal proliferation or vasculitis** with **fibrinoid necrosis and thrombosis**

Answer 105

* **Reactivation** due to immune suppression * Common cause of neurological symptoms in **AIDS patients** * **Multiple small abscesses** in _deep grey matter_

Answer 106

* Blood-borne from maternal infection causing **necrotizing CNS lesions in the fetus** that may calcify * Pregnant women shouldn’t clean the cat litter box * **Multifocal, calcific, necrotizing lesions** results in **severe brain damage**

Answer 107

* Slow infections * Long incubation periods that can last decades * Caused by **conventional viruses** (JC virus and measles) or **unconventional agents** (prions) * Once sx manifest, death is inevitable within 1 to 2 years

Answer 108

* **Persistent, chronic measles infection** * Rare (7 in 1 mil cases) ⇒ ↓ since intro of live measles vaccine * **Vaccination w/ attenuated virus protects against SSPE** * Children or young adults * **Manifests 5-8 years after initial measles virus infection** * **Results in death within 2 years of onset**

Answer 109

* **Variant or altered measles virus** ⇒ ∆ **M protein** (involved in virus assembly) * ∆ Budding ⇒ ⊗ release of progeny virus ⇒ **accumulation of defective virus in neurons** * **Very high levels of anti-measles Ab found in CSF and serum** * Lack of Ab to M protein

Answer 110

* Slowly progressive degenerative neurological disorder * Characterized by **demyelination in multiple brain regions** * **Spasticity, loss of motor skills, seizures, progressive dementia** * Microscopic: * **Brain atrophy** and **gliosis** * **Inclusions** in _oligodendrocytes and neurons_ * EM: **defective measles virus** ⇒ nucleocapsids

Answer 111

JC Virus and BK Virus * Belongs to the papovavirus family * **Naked circular dsDNA genome** * **Replicates and assembled in the nucleus** * Most individuals acquire asymptomatic infection during childhood * ~ 65% infected by age of 14 * Latency → immunosuppression → reactivation * Immunocompetent adults reactivate and shed virus periodically * 40% of immunocompromised secrete JC or BK in urine

Answer 112

* Latent polyoma virus * **Causes renal disease in immunosuppressed hosts** * Causes **nephropathy in ~ 5% of kidney recipients** * May result in loss of a transplanted kidney * **Viremia in 50% of bone marrow transplant recipients** * Ureteral stenosis, hemorrhagic cystitis

Answer 113

**R****eactivation of latent *polyoma virus (JC virus)*** * Asymptomatic infection during childhood (65%) * Virus remains latent in the kidney * Immunosuppression ⇒ viral replication ⇒ dissemination to CNS ⇒ progressive disease * **Complication of AIDS (5-10%)** * **Lytic infection** destroys _oligodendrocytes_ ⇒ **widespread demyelination** * **Severe neurologic disability** * Speech, vision, paralysis → death * No Ab produced * Median survival of 6 months

Answer 114

**Transmissible Spongiform Encephalopathies** * Infectious agent composed of a **misfolded protein (prion)** * No nucleic acid has been found ⇒ **do not replicate** * May be sporadic, familial or transmissible (infectious) * A**ll known prion diseases ∆ structure of the brain or other neural tissue** * All are currently untreatable and universally fatal

Answer 115

**Proteinaceous Infectious Particle** * **Normal prion protein (PrP^C)** encoded by a cellular gene (PRNP) * Highest level of expression in the CNS * Unknown function but normally found on cell surface * Normal 3D configuration (helical) ⇒ _susceptible to digestion by proteases_ * **Abnormal prion form (PrP^SC)** ⇒ identical AA sequence but **3D folding differs** (β sheet) ⇒ _resistant to protease digestion_ * Found within vacuoles instead of cell membrane

Answer 116

* **Ingestion of infected food** * **Improperly sterilized surgical equipment** (neurosurgery) * **Infected blood products** * American Red Cross Deferral for Donors: * Persons who have spent long periods of time in countries where "mad cow disease" is found (UK) are not eligible to donate * Related to concerns about variant Creutzfeldt Jacob Disease (vCJD)

Answer 117

When a prion enters a healthy organism ⇒ **induces existing, properly folded proteins to convert into disease-associated, prion form** * PrP^SC can form dimers with PrP^C and 'teach' it to form the abnormal configuration * ↑ formation of PrP^C ⇒ converted into PrP^SC * T_½ of days instead of hours like normal cellular form * Found inside cytoplasmic vesicles within cells and is secreted * Accumulation of non-degradable PrP proteins in the brain ⇒ **neurological degeneration** * **No immune activation or inflammation is detected**

Answer 118

**Spongiform change** * Vacuolation of neurons * Diffuse astrocytosis and cellular loss * Formation of eosinophilic amyloid plaques and fibrils comprised of aggregated PrP^SC

Answer 119

* Caused by a specific mutation in the ***PRNP* gene** * Mutation causes asparagine → aspartate at residue 178 of PrP^C * **Results in FFI** when it occurs in a *PRNP* allele encoding **methionine at codon 129** * **Results in CJD** when present in tandem with a **valine at this position** * How these amino acids influence disease phenotype is not understood

Answer 120

* Found in **sheep and goats** * Clinically recognized for more than 250 years * **Intense itching** ⇒ scrape body against fixed objects * **Progressive behavioral changes, tremors, ataxia and paralysis** * Spinal cord pathology

Answer 121

* Fore tribe in New Guinea * Similar presentation to CJD (with intense itching) except for the absence of dementia * **Shaking, difficulty walking, and difficulty swallowing** * **Incubation period 4-20 years** * Death in ~ 1 year * **Transmissible agent passed during food preparation for cannibalism** * Cannibalism abolished ⇒ ↓ cases * **Women and children** primarily affected

Answer 122

**Subacute dementing illness with myoclonic jerks** Sx include **radial loss of muscle control and speech, tremors, shivering and dementia** * **Sporadic CJD (90%)** * Mutation in one neuron * Arises in pts with no known risk factors * Most common type * Onset \> 70 y/o * **Hereditary CJD (10%)** * Mutation in germline * ⊕ Fhx and/or ⊕ for genetic mutation associated with CJD * Onset \< 60 y/o but wide range * **Acquired CJD (\< 1%)** * Transmitted by contact with brain or nervous system tissue * Usually iatrogenic ⇒ injection, corneal transplant, transfer of pituitary material, contaminated neurological equipment * No evidence of transmission via casual contact with a CJD patient * Incubation period 2-30 years

Answer 123

**Bovine Spongiform Encephalitis (BSE)** “Mad Cow Disease” * **Developed when infected feed was fed to cows that entered the human food chain** * Most prevalent in the UK * American Red Cross Deferral for Donors: * Persons who have spent long periods of time in countries where "mad cow disease" is found (UK) are not eligible to donate. * This requirement is related to concerns about variant Creutzfeld Jacob Disease (vCJD)

Answer 124

* Ingested prions accumulate in **gut secondary lymphoid tissue** * Travel **lymphatogenously** * Access **neurons** and travel up neurons to the **brain/CNS** * There may be **genetic susceptibility to ingested/acquired prion diseases** * Polymorphisms in certain codons of the PrP protein may confer susceptibility * Homozygosity at codon 129 is present in 95% of CJD cases and 100% of nCJV

Answer 125

* **Clinical diagnosis initially** * Confirmed by **immunohistochemistry** of the brain on autopsy (CJ and vCJ) * vCJD can be dx by **immunoblot of PrP** using tonsil biopsy tissue * Elevated CSF protein **14-3-3** (marker of brain cell death) may have potential dx value

Answer 126

* **Progressive cerebellar ataxia** * Autosomal dominant * Onset earlier ~ 50 y/o * Longer duration

Answer 127

* **Intractable and progressive insomnia, ataxia, autonomic disturbances, stupor, and finally coma** * Caused by a **specific mutation in the *PRNP* gene** * Mid-life onset * Disease course typically less than 3 years * A non-inherited form of the disorder (fatal sporadic insomnia) has also been described

CNS Infections Flashcards

(157 cards)