meningitis agents of infant-->elderly

Question 1

Streptococcus pneumoniae

Answer 1

Gram-positive, lancet-shaped diplococcus

Not fastidious, grows on blod agar – alpha hemolytic.

aerotolerant anaerobe - catalse negative

Question 2

S. pneumo virulence factors

Answer 2

Encapsulated (90 serotypes):

antiphagocytic.

little or no crossreactivity among capsular types relates to possibility of multiple infections.

coagulase negative

Question 3

S. pneumo Incidence and Prevalence:

Answer 3

Most common infectious agent associated with patients with RECURRENT meningeal infections.

Of the 7 major agents of bacterial meningitis, the HIGHEST CASE FATALITY RATE occurs with pneumococcal meningitis

Question 4

S. pneumo peaks in what age groups ??

Answer 4

young (infants and children

Question 5

S. pneumo Risk Factors

Answer 5

Patients may have:
antecedent RT infections → pneumonoccal pulmonary infections.

CSF leaks → recurrent meningeal infections
consistent with the presence of CSF

Invasive Pneumococcal Disease (IPD

Question 6

CSF leaks occur in patients with:

Answer 6

history of head trauma.
congenital defect

*it is not uncommon to observe CSF leakage through ear or nose; If the fluid contains β2-transferrin, that finding consistent with the presence of CSF

Question 7

a common complication of pneumococcal pneumonia that occurs in many (@25→ 30% of all) cases ??

Answer 7

meningitis?

Question 8

Invasive Pneumococcal Disease (IPD)

Answer 8

Disease in which agent has been isolated from a normally sterile site:
blood
CSF
synovial fluid

Question 9

S. pneumo pathogenesis

Answer 9

Primary site of damage is the hippocampus due to neuronal injury/loss via induced apoptosis

If pneumococcal bacteremia occurs, may produce petechial-purpuric skin lesions (AKA symmetrical peripheral gangrene (SPG) but no organisms are present in the lesion. (Indistinguishable in appearance from purpura fulminans caused by N. meningitidis, except that the pneumococcus is not in the lesion)

Question 10

S. pneumo tx

Answer 10

IV cefotaxime (an extended-spectrum cephalosporin, 200 mg/kg/d) and continuous infusion vancomycin (60mg/kg/d after a loading dose of 15mg/kg) with adjunctive therapy with dexamethasone (10 mg every 6 hours) until strain is proven penicillin-sensitive (penicillins)

Adjunctive therapy with dexamethasone

Penicillin susceptible (PenicillinS) S. pneumo is treated with penicillin

Question 11

Penicillin nonsusceptible S. pneumoniae (PNSP) include both

Answer 11

intermediately resistance to penicillin
full resistance to penicillin.

Resistance to other antibiotics also appeared along with penicillin resistance:

Trimethoprim-Sulfamethoxazole,
Macrolides; Erythromycin resistance is common (@ 20%) in USA
Fluoroquinolones

Question 12

Drug-resistance S. pneumoniae (DRSP)

Answer 12

present and increasing in US

due to mutations in PBPs (AKA transpeptidases).

(Resistance to cephalosporins is also increasing, but may be effective)

Strains resistant to penicillin are often resistant to at least one other antibiotic, thus penicillin (the drug) resistance is a marker for resistance to several drugs

Question 13

Multiply drug resistant (MDR) S. pneumoniae (MDRSP)

Answer 13

are resistant to >3 classes of antibiotics.

Question 14

Vancomycin tolerance

Answer 14

(antibiotic is now static, no longer tidal):

First step in acquisition of vancomycin resistance is occurring in a small percentage of community-circulating strains.

Vancomycin tolerance occurs with penicillin, aminoglycoside and quinolone tolerance.

Clinically Important, related to relapses, esp. in pediatric cases of pneumococcal meningitis.

Question 15

Prophylaxis to prevent S. pneumoniae disease:

Answer 15

23 valent polysaccharide vaccines (PPV23; Type II, T-cell independent antigen; Pneumovax or Pnu-immune) (pneumonia in elderly)

conjugated vaccine (T-dependent antigen; PCV-7 AKA Prevenar [7 valent vaccine]) is FDA approved and has resulted in a significant decreases in pneumococcal meningitis (kiddos)

Question 16

Neisseria meningitidis – Meningococcal Meningitis spp.

Answer 16

Two pathogenic species:
N. meningitidis (the meningococcus).
N. gonorrhoeae (the gonococcus).

Nonpathogenic species:
NF of URT and other mucosal surfaces in the human body.
Many nonpathogenic species are non-encapsulated variants of the encapsulated/disease-causing strains of N. meningitidis

Question 17

Characteristics of Neisseria meningitidis (the meningococcus):

Answer 17

Gram-negative diplococcus - kidney-bean shaped
oxidase positive
fastidious.

Question 18

N. meningitidis Virulence factors and surface antigens

Answer 18

Group specific polysaccharide capsule (lipid moiety integrated into O.M.)

All infectious meningococcus are encapsulated and are grouped, based largely on the serological differences in capsular types.
Numerous groups exist; important groups:
A, B, C, Y, W-135, X

Capsular polysaccharide is antiphagocytic.

Group-specific antibodies do not significantly cross-react.

Type B capsule and E. coli K1 capsule have the same chemical composition (sialic acid); sialic acid is a human self antigen, hence are poorly immunogenic.

Question 19

N. meningitidis Possess ??? instead of LPS

Answer 19

Lipooligosaccharide (LOS):

consists of Lipid A (endotoxin) + extended core (no antigenic side chain).

is antiphagocytic by molecular mimicry

causes Disseminated Intravascular Coagulopathies (DIC) because contains lipid A.

Question 20

N. meningitidis Endemic patterns (in the US):

Answer 20

Case rate is low (0.5 → 1.1/100,000 population).

Major serogroups are B, C, Y
Serogroup B causes ½ of all infection in the US.

Serogroup Y infected patients are more likely to be older, manifest with pneumonia.

Question 21

N. meningitidis Epidemic patterns:

Answer 21

countries where meningococcal disease is hyperendemic or epidemic – Africa and Middle Eastern countries.

in North America vs the rest of the world: Specific serogroups of meningococci are associated with epidemics, which occur in cycles.

Question 22

N. meningitidis transmission

Answer 22

via aerosols, respiratory droplets

POE and initial site of colonization is the nasopharynx

Question 23

N. meningitidis Host and source:

Answer 23

humans are the only reservoir for all Neisseria sp.
Non-immune and short-term, group-specific immune carriers exist.

Carrier state duration is highly variable (days → 10 m); chronic carriers do occur.
Carriers are common in epidemics, but few develop disease (1case/1,000 carriers).

Non-immune and immune carriers are largely responsible for spread of disease via aerosols because their numbers are so great vs. diseased patient

Question 24

N. meningitidis age groups

Answer 24

infants and children (1 month → 24 months-o-age)

older children/adolescents (6 → 19 y-o-age).

young adults (19 → 22 y-o-age):
military recruits.
college students living in dorms.

Question 25

N. menigitidis seasonality

Answer 25

Late fall → winter → early spring | crowding

Question 26

N. meningitidis risk factors

Answer 26

Close contact, crowding → increased risk of exposure and infection. Susceptibility (lack of group-specific antibodies): living in a college dormitory or basic training in the military increases a susceptible persons’ increased risk of exposure to new groups of meningococci

Question 27

N. meningitidis Undefined predisposing conditions: (FYI?)

Answer 27

antecedent RT may predispose host to infection, intimate kissing. tobacco smoke exposure (direct or pasive), bar patronage, household crowding, binge drinking, low socioeconomic status,

Question 28

N. meningitidis: Susceptible populations in which disease predominates:

Answer 28

Infants → Young adults (1 month → 22 y-of-age). Families (familial spread) and close contacts. Genetic predisposition to infection and more severe disease is documented, i.e., some (20% of all) patients with meningococcal meningitis also possess properdin, complement (C3, homozygous C4b, C5, C6, C7, C8), or other deficiencies. (esp. C5-C9-terminal)

Question 29

N. meningitidis pathogenesis

Answer 29

After colonization of nasopharynx, the organism invades the blood (meningococcemia) and then from the blood, invades the meninges: Thrombosis→DIC results from loss of thrombomodulin & protein C receptor (these are down-regulated by inflammatory cytokines). Thus activated protein C and not unactivated protein C is required to decrease DIC in your patient.

Question 30

Immunity to N. meningitides is provided by several components of the immune system:

Answer 30

Humoral anticapsular antibodies are protective. Most adults have protective antibody to at least some groups. Complement system is also necessary for protection.

Question 31

Clinical Manifestations of Neisseria meningitidis | aged 16 years or younger:

Answer 31

Early symptoms of sepsis occurred in 72% of children at a median time of 8 hour: leg pains. cold hands and feet. abnormal skin color. Late symptoms: meningism and impaired consciousness occur about 13 to 22 hours after onset of early symptoms.

Question 32

Clinical Manifestations of Neisseria meningitides: adults

Answer 32

Early symptoms may occur and consist of only mild pharyngitis without exudate, slight fever, and headache at onset OR several days of flu-like symptoms with emesis then the classic symptoms of meningitis occur OR classic symptoms without early symptoms occur

Question 33

Besides the classic clinical manifestations of meningitis, petechial (non-blanching, hemorrhagic) rash on ankles and wrist (first) then trunk, thigh, forearms may appear if ?? also present

Answer 33

septicemia

Question 34

Patients may survive disease without or with significant sequelae from N. meningitidis, which include:

Answer 34

nerve deafness CNS damage necrosis of large areas of skin or tissues often results in amputation

Question 35

Waterhouse-Friderichsen syndrome

Answer 35

fulminant meningococcemia characterized by: circulatory shock due to SIRS → severe sepsis or septic shock. bilateral hemorrhagic necrosis of adrenals → low cortisol leves → hypotension disseminated intravascular coagulation *not limited to N. meningitidis; this disease is seen in certain other fulminant bacterial diseases

Question 36

Purpura fulminans AKA symmetrical peripheral gangrene (SPG): meningococcemia +/- meningitis: complications

Answer 36

``` hypothermia. seizures. shock. thrombocytopenia. leukocytosis. purpura - meningococcus is in the lesions. ``` highest mortality rate (15→50%) occurs with Group C disease, esp. in persons with purpura fulminans, even with appropriate treatment *not limited to N. meningitidis; this disease is seen in certain other fulminant bacterial diseases

Question 37

Other meningococcal infections:

Answer 37

meningococcemia without CNS localization. Meningococcus isolated from areas which are the domain of gonococci. pneumonia or endocarditis.

Question 38

Laboratory Diagnosis N. meningitidis:

Answer 38

Microscopic examination and culture of skin lesions (aspirant or biopsy) If petechial or purpuric lesions are present, Gram-stain of lesion biopsy will often (50% of the time) reveal meningococcus (unlike S. pneumo, will NOT be in lesion) Determine antibiotic sensitivity – resistance to many drugs is documented; *MBC required* Obtain nasopharyngeal cultures to screen for carriers, treat carriers with rifampin

Question 39

N. meningitidis tx

Answer 39

ceftriaxone, or cefotaxime or penicillin G Other treatments: Bacteriocidal/permeability-increasing protein, recombinant rBPI

Question 40

N. meningitidis morb/mort (with tx)

Answer 40

Among survivors, neurological sequelae/loss of limb is low (10→20%). Mortality with uncomplicated meningococcal meningitis is low (10%) Meningococcal meningitis with meningococcal septicemia; Mortality without shock is high (20%). *with shock is very high (60%)*

Question 41

N. meningitidis ppx of HCW

Answer 41

Wear a mask (face shield) within 3 feet of pt. known or suspected to be infected with meningococcemia (or other microbial agent) transmitted by droplet nuclei (>5μ) that can be generated during coughing, sneezing, talking, performing clinical procedures. If no mask/shield is worn, consider antibiotic prophylaxis. Risk is small, but real, highest in those involved with airway management, i.e., the physician

Question 42

N. meningitidis vaccines

Answer 42

Tetravalent/quadrivalent polysaccharide vaccine for Groups A, C, Y, W-135 ([MPSV4]; Menomune® Tetravalent/quadrivalent (groups A, C, Y, and W-135) polysaccharide diphtheria toxoid conjugate vaccine [MCV4] Menactra®

Question 43

Tetravalent/quadrivalent polysaccharide vaccine for Groups A, C, Y, W-135 ([MPSV4]; Menomune® limitations??

Answer 43

a type II, T-independent antigen vaccine – Administered subcutaneous (SC) limitations: capsular material is a type II, T-independent antigen: Poor immunogenicity in infants (

Question 44

Tetravalent/quadrivalent (groups A, C, Y, and W-135) polysaccharide diphtheria toxoid conjugate vaccine ([MCV4], Menactra®

Answer 44

Administered intramuscular (IM) – SC misadministration results in lower serum Ab titer. This is a T-dependent antigen vaccine Vaccine is a T-dependent vaccine so should: stimulate immunity for eliminate nasopharyngeal carriage thus prevent transmission of infection. Vaccine should reduce the prevalence of meningococcal disease by 75→ 90%.

Question 45

Vaccines for protection against ?? infection are now approved by the FDA:

Answer 45

serogroup b multivalent vaccines with OM components that either are common or rare but all are highly conserved in all strains of B 4CMenB vaccine (Bexsero): Trumenba

Question 46

The CDC advisory panel recommends that these serogroup B N. meningitides vaccines be administered to high risk populations such as ??

Answer 46

People with persistent complement component deficiencies. Persons receiving the drug eculizumab (Soliris) also are at increased risk because the drug binds to C5 and inhibits the terminal complement pathway Patients with anatomic or functional asplenia People at increased risk owing to an outbreak of serogroup B meningococcal disease not currently recommended for routine use in first-year college students living in residence halls, military recruits, or all adolescents; physicians should determine vaccination needs for 16-23 year olds on an individual basis; recommendations for broader use of MenB vaccines in adolescents and college students will be considered separately by the ACIP

Question 47

Elimination of the carrier state (nasopharyngeal carriage of N. meningitidis ) by chemoprophylaxis with ?? timeframe??

Answer 47

rifampin, ciprofloxacin, or ceftriaxone or azithromycin (unless fluoroquinolone-resistant N. meningitidis is detected in the area, if that is so, then ciprofloxacin should not be administered) preferably within 24 hours of identification of the index case and no longer than 14 days after onset of illness in the index case and/or vaccination with Menactra of family members and close contacts of persons with disease.

Question 48

For clusters (i.e., for children K → 12; a second case of meningococcal disease within 30 days of the first/index case) or small outbreaks, ppx with ??? is effective

Answer 48

abx

Question 49

For large outbreaks (whole counties, cities, etc.), ?? (if the strain responsible for the outbreak is A, C, Y, W-135) as well as ?? of family members and close contacts of persons with disease are most effective.

Answer 49

vaccination | antibiotic prophylaxis

Question 50

Cryptococcal meningitis caused by the fungus, Cryptococcus neoformans is usually a ??

Answer 50

subacute or chronic disease which is fatal if not treated

Question 51

Cryptococcus neoformans

Answer 51

basidiomycete (Cn) - Opportunistic pathogen that predominantly infect immunocompromised persons: Cn variety (var): * var. grubii* (CnVG; serotype A) - major causative agent worldwide. var. neoformans (CnVN; serotype D) - prominent in central Europe. var. AD, a hybrid diploid.

Question 52

C. gattii

Answer 52

(Cg; serotype B and C; AKA Cryptococcus bacillisporus): A primary pathogen that predominantly infects immunocompetent persons

Question 53

CnVN and CnVG distribution

Answer 53

Worldwide distribution (including rural and urban settings), Found in soil, especially those enriched by avian guano, where it exists as a small (

Question 54

Cg distribution

Answer 54

Previously thought to be restricted to tropical and subtropical climates with a special ecologic niche on Eucalyptus trees. However, the recent outbreak of Cg infection in healthy humans (pneumonia &/or meningitis) and animals in the temperate climate of Vancouver Island, British Columbia, Canada and its isolation from several species of trees other than Eucalyptus as well as soil have raised the strong possibility that this fungus might have broader geographic distribution.

Question 55

Cn Growth Characteristics: The infectious form for humans and the pathogenic form in humans is the ?? Possess a sexual cycle, but ?? are NOT involved in infection or disease.

Answer 55

asexual yeast form. Not thermally dimorphic, like other agents of systemic mycosis. hyphae, spores

Question 56

Crypto Virulence factors:

Answer 56

Capsule (glucuronoxylomannan GXM): antiphagocytic prevents antigen processing. Phenoloxidase (laccase) production: antiphagocytic. results in increased resistance to amphotericin B may also be responsible for agent’s neurotropism?

Question 57

Cn/Crypto incidence/prev. 3rd most common cause of ?? after ?? 4th most common ?? after ??

Answer 57

CNS infection in advanced HIV/AIDS patients after HIV and Toxoplasmosis OI -opportunistic infection in advanced HIV/AIDS patients after P. jiroveci (PCP), CMV, M. avium complex.

Question 58

Crypto Transmission and Reservoirs

Answer 58

For any strain of C. neoformans that can produce an infection in any patient population, person-to-person transmission is NOT believed to occur, even among AIDS patients. Primary POE is the *RT* with hematogenous spread to CNS.

Question 59

Crypto age, gender, seasonality

Answer 59

NONE

Question 60

Crypto Risk Factors: Cg (gatti)

Answer 60

causes cryptococcosis in *immunocompetent* individuals in tropical/subtropical regions (e.g., California in the US). incidence of disease is rare, but increasing. rarely causes disease in advanced HIV/AIDS pt (explanation unknown). no predisposing factor(s) known.

Question 61

Crypto Risk Factors: CnVN AND CnVG:

Answer 61

case distribution is sporadic and worldwide rarely causes disease in immunocompetent patient. causes cryptococcosis in *immunocompromised or immunosuppressed* individuals:

Question 62

immunocompromised/immunosuppressed individuals (@ risk for Crypto -CnVN and CnVG) include:

Answer 62

Impaired cell-mediated immunity: advanced HIV/AIDS,; lymphoreticular malignancies, patient receiving chronic, high-dose corticosteroid, immunosuppressive therapies for SOT pts Infection and disease occurs in some (@ 5→10% of) advanced HIV/AIDS patients → a persistent infection. Advanced HIV/AIDS pt. that survives initial presentation requires life-long therapy.

Question 63

primary sites of infection for var. grubii and var. neoformans:

Answer 63

lungs and CNS | Primary POE is the respiratory tract with hematogenous spread to CNS

Question 64

In immunocompetent patients w. Cn

Answer 64

asymptomatic pulmonary infection are usual.

Question 65

In immunocompromised patients, especially advanced HIV/AIDS patient, with Cn

Answer 65

disease is more common and progression of disease tends to be more rapid Lung infections are variable: mild, sustained febrile illness with normal radiographs → fulminant course with shock and/or ARDS. ``` Most commonly in the AIDS patient, S/S similar to PCP; Over 2 → 4 weeks, symptoms develop: fever, cough dyspnea weight loss, headache. ``` CXR reveals interstitial infiltrates (focal or diffuse).

Question 66

Cn Meningoencephalitis: involves ?? ICP??

Answer 66

A progressive infection mostly involving basal ganglia and cortical gray matter: Elevated Intracranial pressure (ICP) >250 mm H2O is common and a significant cause of mortality in these patients.

Question 67

Cn Meningoencephalitis presentation

Answer 67

``` Usually subacute with insidious onset. Over 2 → 4 weeks, symptoms develop: headache. fever. lethargy. nausea, vomiting. minimal nuchal rigidity. ``` ``` symptoms progresses on to focal signs: personality change (altered mental status-behavior) impairment of higher mental functions (memory, cognition, language) ``` ends with coma and death.

Question 68

Cn in In advanced HIV/AIDS and severe T-cell compromised patients: Besides the 2 primary sites which are the Lungs and CNS:

Answer 68

Organism is much more likely to disseminate to any organ, especially: skin (every kind of lesion is possible: cutaneous cryptococcosis] may mimic many cutaneous disorders, including molluscum contagiousum, acne vulgaris, squamous cell cancer, or even cellulitis (can be the sentinel finding of disseminated disease) also: eye bone urinary tract

Question 69

Cryptococcal polysaccharidemia/antigenemia: | In advanced HIV/AIDS and severe T-cell compromised patients

Answer 69

positive serum antigen assay without detection of fungi from any body site (i.e., negative results by visualization or growth or histochemical staining). Occurring with increasing frequency in advanced HIV/AIDS infected patient due to increased antigen testing. There is no data on how many persons with antigenemia will develop disease Since this is a fatal disease and treatment is available, *all patients with positive serum antigen must be treated*

Question 70

Crypto: EC or IC?

Answer 70

faculataitve intracellular pathogen of macrophages: can replicate in the phagosome of macrophages → macrophage lysis and release of the agent. An extrusion/explusion mechanism allows the agent to be released from macropahges without lysing the macrophage and avoiding a host inflammatory responses.

Question 71

ddx meningoencephalitis for an AIDS patient:

Answer 71

HAD (HIV-assoc. dementia): Primary or metastatic brain tumor – EBV-associated primary CNS lymphoma. Toxoplasmosis encephalitis PML Cryptococcal meningoencephalitis CMV polyradiculopathy, encephalitis, myelopathy, etc.

Question 72

for Crypto dx, obtain samples of:

Answer 72

``` CSF blood, urine, sputum and other respiratory samples, biopsied tissues. ```

Question 73

Test cypto samples by:

Answer 73

``` Serologic tests (latex agglutination test, ELISA) to detect presence of capsular antigen: serum CrAg-Its presence is highly predictive of development of CM within 1 yr. ``` Culture on routine mycological or bacteriological media (blood agar). Microscopic examination of sedimented CSF: -with India ink preparation reveals 5→7 μm spherical, capsulated yeasts forms cells of macrophage/monocyte lineage. -by Gram-stain reveals Gram-positive eucaryotic cells: (All yeast, including cryptococcus, stain Gram-positive by Gram stain) Others: Mucicarmine stain. Papanicolaou prep. Hematoylin and eosin (H/E).

Question 74

Crypto Radiology:

Answer 74

CXR or CT for pulmonary involvement CT or MRI for meningitis.

Question 75

Crypto tx

Answer 75

High dose amphotericin B (0.7mg/kg IV) with 5-fluorocytosine (100mg/kg/day) for 2w. Fluconazole (400mg PO) or itraconazole for 8 weeks. -Maintain with fluconazole (200mg PO daily) life-long unless relapse occurs. Drug resistance is rare. Treat elevated ICP. Prognosis is poor in the absence of HAART: 10-25% die during initial presentation and 30-60% succumb within 1 year.

Question 76

Crypto prevention

Answer 76

NONE

Question 77

AMOEBIC and ACUTE PRIMARY MENINGOENCEPHALITIS

Answer 77

A very rare diseases confined to the CNS that is produced by amoebae (protozoa).

Question 78

Amoebae possess 2 cellular forms:

Answer 78

trophozoites are the feeding form found in brain and in the environment cyst are the resistant form found in water, NEVER BRAIN -resistant to freezing water and chlorination

Question 79

Naegleria fowleri

Answer 79

ubiquitous, free-living amoebae found in warm, freshwater lakes, puddles, ponds, improperly chlorinated swimming pools and brackish water especially during *hot weather summers*

Question 80

Population at risk for acute primary amoebic meningoencephalitis:

Answer 80

Children and young adults; Seasonal occurrence = summer - swimming/waterskiing in warm, fresh water. Patients are usually healthy, immunocompetent before disease (but immunocompromised persons are equally susceptible). 1/2 of all cases worldwide occur in the US (~1case/y in the US until last year; when 6 cases occurred).

Question 81

Acute primary amoebic meningoencephalitis (PAM) Infections occurs when water bearing the agent forced into the POE which is the ???

Answer 81

nose-->the organism is implanted in the nasal mucosa from which it invades the CNS through the cribriform plate and can be found in the subarachnoid and perivascular spaces. (*Inflammatory disease*)

Question 82

acute PAM disease duration ?? incubation period?? manifests with ?? death from ??

Answer 82

Fulminate course 2 → 7 days from onset of symptoms to death. After a short (2 → 4 d) incubation period, patient manifests with s/s similar to those of acute bacterial meningitis and/or encephalitis. 1 → 2 days after symptom first appear, pt. manifests with diffuse encephalitis then coma. Death occurs 2 → 7 days later due to cardiorespiratory failure, cerebral edema.

Question 83

dx PAM

Answer 83

difficult due to non-specific symptoms and rapid progression of disease

Question 84

?? is essential in diagnosis of PAM

Answer 84

Patient history: Hyperacute clinical course. Unrelenting signs and symptoms. Exposure to fresh water

Question 85

In PAM: CSF findings similar to those of bacterial meningitis (PMNs predominate, etc.) except may observe ??? also:

Answer 85

amoeba in CSF: Cloudy fluid. PMNs predominate Hyperproteinosis (elevated protein levels). Hypoglycorrhachia (low glucose). *Absence of viral, bacterial or fungal agents*, none detected by staining, culture, PCR, rapid tests, etc.

Question 86

other PAM dx clues

Answer 86

Peripheral leucocytosis | *Death within a week*

Question 87

PAM Brain biopsy specimen reveals:

Answer 87

Positive IFA test with anit- Naegleria fowleri serum. Clusters of amoebic trophs by H/E stain Intense PMN infiltrate/inflammation in brain parenchyma

Question 88

PAM px

Answer 88

Prognosis is very poor – high mortality, those who survive have catastrophic, irreversible brain damage.

Question 89

PAM tx

Answer 89

Amphotericin B - intrathecally and/or intraventricularly Miltefosine

Question 90

Miltefosine:

Answer 90

An investigational antineoplastic drug (breast cancer) and antiprotozoal drug (anti-leishmania drug and N. flowerii), now HIV therapy by targeting HIV infected macrophages: Akt inhibitor/Protein Kinase B (PKB), a serine/threonine-specific protein kinase Miltefosine targets HIV infected macrophages, which play a role in vivo as long-lived HIV-1 reservoirs. The HIV protein Tat activates pro-survival PI3K/Akt pathway in primary humanmacrophages. Miltefosine acts by inhibiting the PI3K/Akt pathway, thus removing the infected macrophages from circulation, without affecting healthy cells.