Cns

MICROBIAL DISEASES OF THE NERVOUS SYSTEMDR SONNIE P. TALAVERA 08162009 OLFU

How Microbes Enter the Nervous System

Skull or backbone fractures Medical procedures Along peripheral nerves Blood or lymph

The Nervous System

Figure 22.1

Microbial Diseases of the Nervous System Bacteria can grow in the cerebrospinal

fluid in the subarachnoid space of the CNS.

The blood brain barrier (capillaries) prevents passage of some materials (such as antimicrobial drugs) into the CNS.

Meningitis: Inflammation of meninges. Encephalitis: Inflammation of the brain.

The Meninges and Cerebrospinal Fluid

Figure 22.2

Bacterial Meningitis

Fever, headache, and stiff neck Followed by nausea and vomiting May progress to convulsions and coma Diagnosis by Gram stain or latex

agglutination of CSF Treated with cephalosporins

Bacterial Meningitis

Figure 22.3

ACUTE BACTERIAL MENINGITIS

infection and inflammation of the meninges

infection of other parts of the CNS

SYMPTOMS(meningeal symptoms)

• high fever• headache• stiff neck• irritability (children)• neurologic dysfunction

• lethargy•confusion

• uncharacteristic sleepiness• vomiting

B. Agents: - vary depending on the age of the patient1. newborns/neonates

• Group B streptococci• E. coli K1• Listeria monocytogenes

2. infants and children up to 24 months old

• Streptococcus pneumoniae• Neisseria meningitidis• (Haemophilus influenzae type b –

vaccine; self study)

3. Adults• Streptococcus pneumoniae• Neisseria meningitidis

Neisseria Meningitis, Meningococcal Meningitis

N. meningitidis Gram-negative aerobic cocci, capsule 10% of people are healthy

nasopharyngeal carriers Begins as throat infection, rash Serotype B is most common in the United

States Vaccination recommended for college

students.

Neisseria Meningitis, Meningococcal Meningitis N. meningitidis causes meningococcal meningitis. This

bacterium is found in the throats of healthy carriers.

The bacteria probably gain access to the meninges through the bloodstream. The bacteria may be found in leukocytes in CSF.

Symptoms are due to endotoxin. The disease occurs most often in young children.

Purified capsular polysaccharide vaccine against serotypes A, C, Y, and W-135 is available.

Neisseria Associated Diseases

(ophthalmia neonatorum)

Differential Characteristics of Commonly Isolated

Neisseria spp.

• Encapsulated small, gram-negative diplococci

• Second most common cause (behind S. pneumoniae) of community-acquired meningitis in previously healthy adults

• swift progression from good health to life-

threatening disease

General Overview of Neisseria meningitidis

Pathogenicity:

• Pili-mediated, receptor-specific colonization of nonciliated cells of nasopharynx

• Antiphagocytic polysaccharide capsule

• hyperproduction of lipooligosaccharide

General Overview of Neisseria meningitidis

• Following dissemination of virulent organisms from the nasopharynx:• Meningitis• Septicemia (meningococcemia) with or

without meningitis• Meningoencephalitis• Pneumonia• Arthritis• Urethritis

Diseases Associated with Neisseria meningitidis

Neisseria meningitidis in Cerebrospinal Fluid

• Humans only natural hosts

• Person-to-person transmission by aerosolization of respiratory tract secretions in crowded conditions

• Close contact with infectious person (e.g., family members, day care centers, military barracks, prisons, and other institutional settings)

Epidemiology of Meningococcal Disease

• Highest incidence in children younger than 5 years and particularly those younger than 1 year of age as passive maternal antibody declines and as infants immune system matures

• Commonly colonize nasopharynx of healthy individuals; highest oral and nasopharyngeal carriage rates in school-age children, young adults and lower socioeconomic groups

Epidemiology of Meningococcal Disease

• Specific receptors (GD1 ganglioside) for bacterial fimbriae on nonciliated columnar epithelial cells in nasopharynx of host

• Organisms are internalized into phagocytic vacuoles, avoid intracellular killing

• Replicate intracellularly and migrate to subepithelial space

Pathogenesis of Meningococcal Disease

• Hyperproduction of endotoxin and blebbing into surrounding environment (e.g., subepithelial spaces, bloodstream)

• most clinical manifestations including • diffuse vascular damage, • vasculitis, • thrombosis, • disseminated intravascular coagulation

Pathogenesis of Meningococcal Disease

Skin Lesions of Meningococcemia

NOTE: Petechiae have coalesced into hemorrhagic bullae.

• Following colonization of the nasopharynx, protective humoral immunity develops against the same or closely related organisms of the same serogroup

• complement system is required for clearance of the organisms

• Cross-reactive protective immunity acquired with colonization by closely related antigenic strains e.g., E. coli K1)

Immunogenicity of Neisseria meningitidis

• Large numbers of encapsulated, small, gram-negative diplococci and PMN seen in cerebrospinal fluid

• Transparent, non-pigmented nonhemolytic colonies on chocolate blood agar with enhanced growth in moist atmosphere with 5% CO2

• Oxidase-positive

• Acid production from glucose and maltose

Laboratory Characterization of Neisseria meningitidis

Prevention and Treatment of Meningococcal Disease

• Penicillin is drug of choice for treatment in adjunct with supportive therapy for meningeal symptoms• Chloramphenicol or cephalosporins as

alternatives

• Chemoprophylaxis of close contacts with rifampin or sulfadiazine (if susceptible)

• Polyvalent vaccine is effective in people older than 2 years of age adjunct to chemoprophylaxis

Neisseria Meningitis, Meningococcal Meningitis

Figure 22.4

Haemophilus influenzae Meningitis Occurs mostly in children (6 months to 4

years). Gram-negative aerobic bacteria, normal

throat microbiota Capsule antigen type b Prevented by Hib vaccine

Haemophilus influenzae Meningitis H. influenzae requires blood factors for

growth there are six types of H. influenzae based on

capsule differences.

H. influenzae type b the most common cause of meningitis in

children under 4 years old.

A conjugated vaccine directed against the capsular polysaccharide antigen is available.

Differential Characteristics

X factor = hemin (hematin)V factor = (NAD or NADP)

nicotinamide adenine dinucleotide

Haemophilus General Overview• Gram-negative bacilli liking blood (as per genus

name)

• Obligate Parasites of Man and Animals• Major pathogens for which humans are natural

hosts

• Haemophilus influenzae • Acute pyogenic, normally invasive infections• Chronic infections with H. influenzae as 2o pathogen

• Haemophilus ducreyi • True pathogen (i.e., not found in healthy

individuals)• STD; Soft chancre (chancroid)

Haemophilus Diseases

Haemophilus influenzae Diseases

HIB VACCINE

• humoral IgG to capsule prevents systemic infection by opsonization

• new vaccine composed of type b carbohydrate coupled to protein has drastically reduced meningitis by Hib

• the vaccine is now part of the standard infant/childhood regimen

Streptococcus pneumoniae Meningitis, Pneumococcal Meningitis

Gram-positive diplococci 70% of people are healthy

nasopharyngeal carriers Most common in children (1 month to 4

years) Mortality: 30% in children, 80% in elderly Prevented by vaccination

Streptococcus pneumoniae Meningitis, Pneumococcal Meningitis

Hospitalized patients and young children are most susceptible to S. pneumoniae meningitis.

It is rare but has a high mortality rate. A conjugated vaccine is available.

Listeriosis Listeria

monocytogenes Gram-negative

aerobic rod Usually foodborne;

it can be transmitted to fetus.

Reproduce in phagocytes.

Figure 22.5

Listeriosis causes meningitis in newborns, the

immunosuppressed, pregnant women, and cancer patients.

Acquired by ingestion of contaminated food, it may be asymptomatic in healthy adults.

L. monocytogenes can cross the placenta and cause spontaneous abortion and stillbirth.

Figure 22.5

Listeria monocytogenes

• Gram-positive beta-hemolytic bacillus

• Multiply at refrigerator temperatures (4oC)

• Tumbling motility at room temperature

• CAMP Test positive (like Group B Streptococcus)

• Intestinal tract of mammals & birds (especially chickens)

• Persists in soil

• Soft cheeses & unwashed raw vegetables

• Raw or undercooked food of animal origin• Luncheon meats

• Hot dogs

• Large scale food recalls have become common

Where do we find Listeria?

Epidemiology of

Listeriosis

Natural Reservoirs

Common Routes for Human Exposure

Population at Greatest Risk

Epidemiology of Listeria Infections

• Neonates, elderly & immunocompromised

• Granulomatosis infantiseptica• Transmitted to fetus transplacentally

• Early septicemic form: 1-5 days post-partum

• Delayed meningitic form: 10-20 days following birth

• Intracellular pathogen• Cell-mediated and humoral immunity develop

• Only cell-mediated immunity is protective

Listeriosis

Methods That Circumvent Phagocytic

Killing

See Chpt. 19

Tetanus Clostridium tetani Gram-positive, endospore-forming,

obligate anaerobe Grows in deep wounds. Tetanospasmin released from dead cells

blocks relaxation pathway in muscles. Prevention by vaccination with tetanus

toxoid (DTP) and booster (dT). Treatment with tetanus immune globulin.

Tetanus produces the neurotoxin tetanospasmin,

which causes the symptoms of tetanus:

Spasms

contraction of muscles controlling the jaw

death resulting from spasms of respiratory muscles.

Tetanus grow in deep, unclean wounds and wounds

with little bleeding. Acquired immunity results from DPT

immunization that includes tetanus toxoid.

Following an injury, an immunized person may receive a booster of tetanus toxoid.

An unimmunized person may receive (human) tetanus immune globulin.

Debridement (removal of tissue) and antibiotics may be used to control the infection.

Tetanus

Figure 22.6

Summary of C. tetani

Infections

Summary of Clostridium tetani Infections (cont.)

Clostridium tetani Gram Stain

NOTE: Round terminal spores give cells a “drumstick” or “tennis racket” appearance.

Clinical Forms of Tetanus

Opisthotonos in Tetanus Patient

Risus Sardonicus in Tetanus Patient

Mechanism of Action of Tetanus

Toxin

Botulism Clostridium botulinum Gram-positive, endospore-forming,

obligate anaerobe Intoxication comes from ingesting

botulinal toxin. Botulinal toxin blocks release of

neurotransmitter causing flaccid paralysis.

Prevention Proper canning Nitrites prevent endospore germination in

sausages.

Botulism Botulism is caused by an exotoxin

produced by C. botulinum growing in foods.

Serological types of botulinum toxin vary in virulence, with type A being the most virulent.

The toxin is a neurotoxin that inhibits the transmission of nerve impulses.

Botulism Type A

60-70% fatality, most heat resistant and proteolytic

Found in CA, WA, CO, OR, NM. Type B

25% fatality,; proteolytic and nonproteolytic Europe and eastern United States

Type E Found in marine and lake sediments Pacific Northwest, Alaska, Great Lakes area Non proteolytic, grow in ref temp and less

anaerobic condition

Botulism Blurred vision occurs in 1 to 2 days

progressive flaccid paralysis follows for 1 to 10 days

possibly resulting in death from respiratory and cardiac failure.

Botulism C. botulinum will not grow in acidic foods

or in an aerobic environment.

Endospores are killed by proper canning. The addition of nitrites to foods inhibits growth after endospore germination.

The toxin is heat labile and is destroyed by boiling (100°C) for 5 minutes

Summary of C. botulinum

Infections

Summary of C. botulinum

Infections (cont.)

Mechanism of Action of

Botulinum Toxin

Botulism

Treatment: Supportive care and antitoxin.

Infant botulism results from C. botulinum growing in intestines.

Wound botulism results from growth of C. botulinum in wounds.

Botulism

For diagnosis, mice protected with antitoxin are inoculated with toxin from the patient or foods.

Diagnosis

Figure 22.8

Leprosy Mycobacterium leprae

causes leprosy, or Hansen’s disease.

Acid-fast rod that grows best at 30°C.

Grows in peripheral nerves and skin cells.

Transmission requires prolonged contact with an infected person.

Mycobacterial Clinical Syndromes

Leprosy

Leprosy is not highly contagious and is spread by prolonged contact with exudates.

Untreated individuals often die of secondary bacterial complications, such as tuberculosis.

Patients with leprosy are made noncontagious within 4 to 5 days with sulfone drugs and then treated as outpatients.

Leprosy occurs primarily in the tropics.

Leprosy

Tuberculoid (neural) form

Lepromatous (progressive) form

•Loss of sensation in skin areas•positive lepromin test

•Disfiguring nodules over body•negative lepromin test

Leprosy Laboratory diagnosis is based on

observations of acid-fast rods in lesions or fluids and the lepromin test.

Acid-Fast (Kinyoun) Stain of Mycobacterium

NOTE: cord growth (serpentine arrangement) of virulent strains

Eight Week Growth of Mycobacterium tuberculosis on

Lowenstein-Jensen Agar

Mycobacterium leprae Infections (cont.)

Tuberculoid vs. Lepromatous Leprosy

Clinical Manifestations and Immunogenicity

Lepromatous vs. Tuberculoid Leprosy

Lepromatous Leprosy (Early/Late Stages)

Lepromatous Leprosy Pre- and Post-

Treatment

Clinical Progression of Leprosy

Leprosy

Figure 22.9

Etiology Mycobacterium leprae.

Transmission

Direct contact

Symptoms Nodules on the skin; loss of sensation.

TreatmentPrevention

Dapsone and rifampin.BCG vaccine.

Susceptible—People living in the tropics; genetic predisposition.

Poliomyelitis Poliovirus Transmitted by ingestion. Initial symptoms: Sore throat and nausea Viremia may occur; if persistent, virus can

enter the CNS; destruction of motor cells and paralysis occurs in <1% of cases.

Prevention is by vaccination (enhanced-inactivated polio vaccine).

Poliomyelitis The symptoms of poliomyelitis

headache sore throat fever stiffness of the back and neck occasionally paralysis (fewer than 1% of

cases)

Poliovirus is transmitted by the ingestion of water contaminated with feces.

Poliomyelitis Poliovirus first invades lymph nodes of the

neck and small intestine.

Viremia and spinal cord involvement may follow.

Diagnosis is based on isolation of the virus from feces and throat secretions.

Poliomyelitis The Salk vaccine (an inactivated polio

vaccine, or IPV) involves the injection of formalin-inactivated

viruses and boosters every few years

The Sabin vaccine (an oral polio vaccine, or OPV) contains three live, attenuated strains of

poliovirus and is administered orally.

Polio is a good candidate for elimination through vaccination.

Poliomyelitis

Figure 22.11

Etiology Picornavirus (poliovirus).

Transmission

Ingestion of contaminated water.

Symptoms Headache, sore throat, fever, nausea; rarely paralysis.

Prevention Sewage treatment.

These vaccinations provide artificially acquired active immunity because they cause the production of antibodies, but they do not prevent or reverse damage to nerve

Rabies Virus (Rhabdovirus) Transmitted by animal bite. Virus multiplies in skeletal muscles, then brain cells

causing encephalitis. Initial symptoms may include muscle spasms of the

mouth and pharynx and hydrophobia. Furious rabies: Animals are restless then highly excitable. Paralytic rabies: Animals seem unaware of surroundings. Preexposure prophylaxis: Infection of human diploid cells

vaccine. Postexposure treatment: Vaccine plus immune globulin.

RABIES Rabies virus (a rhabdovirus) causes an

acute, usually fatal, encephalitis called rabies. Rabies may be contracted through bite of a

rabid animal by inhalation of aerosols invasion through minute skin abrasions

The virus multiplies in skeletal muscle and connective tissue.

RABIES Encephalitis occurs when the virus moves

along peripheral nerves to the CNS. Symptoms of rabies include

spasms of mouth and throat muscles followed by extensive brain and spinal cord damage

death.

RABIES Laboratory diagnosis may be made by direct FA tests

of saliva, serum, and CSF or brain smears. Reservoirs for rabies in the United States include

skunks, bats, foxes, and raccoons. Domestic cattle, dogs, and cats may get rabies. Rodents and rabbits seldom get rabies.

Current postexposure treatment includes administration of human rabies immune globulin (RIG) along with multiple intramuscular injections of vaccine.

Preexposure treatment consists of vaccination. Other genotypes of Lyssavirus cause rabies-like

diseases.

How Is Rabies Transmitted?

How Is Rabies Transmitted?

How Is Rabies Transmitted?

Rabies Virus (Rhabdovirus)

Figure 22.12

Rabies Virus (Rhabdovirus)

Figure 22.13

Arboviral Encephalitis Arboviruses are

arthropod-borne viruses that belong to several families.

Prevention is by controlling mosquitoes.

Figure 22.14

Arboviral Encephalitis

Symptoms of encephalitis are Chills Headache Fever Coma

Many types of viruses (called arboviruses) transmitted by mosquitoes cause encephalitis.

Arboviral Encephalitis The incidence of arboviral encephalitis

increases in the summer months, when mosquitoes are most numerous.

Notifiable arboviral infections are eastern equine encephalitis (EEE), western equine encephalitis (WEE), St. Louis encephalitis (SLE), California encephalitis (CE), West Nile virus (WNV).

Arboviral Encephalitis

Diagnosis is based on serological tests.

Control of the mosquito vector is the most effective way to control encephalitis.

Arboviral Encephalitis

Encephalitis Reservoir Mosquito vector U.S. distribution

Western equine Birds, horses Culex

Eastern equine Birds, horses Aedes, Culiseta

St. Louis Birds Culex

California Small mammals Aedes

West Nile Birds,

mammalsCulex, Aedes

Cryptococcus Neoformans Meningitis (Cryptococcosis)

Figure 22.15

Cryptococcus Neoformans Meningitis (Cryptococcosis)

Soil fungus associated with pigeon and chicken droppings.

Transmitted by the respiratory route; spreads through blood to the CNS.

Mortality up to 30%. Treatment: Amphotericin B and

flucytosine.

Cryptococcus Neoformans Meningitis (Cryptococcosis Cryptococcus neoformans is an

encapsulated yeastlike fungus that causes cryptococcosis.

The disease may be contracted by inhalation of dried infected pigeon or chicken droppings.

The disease begins as a lung infection and may spread to the brain and meninges.

Cryptococcus Neoformans Meningitis (Cryptococcosis Immunosuppressed individuals are most

susceptible to Cryptococcus neoformans meningitis.

Diagnosis is based on latex agglutination tests for cryptococcal antigens in serum or CSF.

African Trypanosomiasis Trypanosoma brucei gambiense infection is

chronic (2 to 4 years).

T. b. rhodesiense infection is more acute (few months).

Transmitted from animals to humans by tsetse fly.

Prevention: Elimination of the vector. Treatment: Eflornithine blocks an enzyme

necessary for the parasite.

Parasite evades the antibodies through antigenic variation.

Tsetse fly. The vector of African trypanosomiasis

African Trypanosomiasis African trypanosomiasis is caused by the

protozoa Trypanosoma brucei gambiense and T. b. rhodesiense and transmitted by the bite of the tsetse fly.

The disease affects the nervous system of the human host, causing lethargy and eventually coma. It is commonly called sleeping sickness.

Vaccine development is hindered by the protozoan’s ability to change its surface antigens.

African Trypanosomiasis

Figure 22.16

TRYPANOSOMA BRUCEI

African trypanosomiasisT. b. gambiense Gambian trypanosomiasis,

West & Mid-African sleeping sickness

T. b. rhodesiense

Rhodesian trypanosomiasis, East African sleeping sickness

TRYPANOSOMA BRUCEI

Lab Dx:

Giemsa stained thick and thin blood smears or lymph exudate (early stage); Giemsa stained smears of CSF (late stage)

A dividing parasite is seen at the right. Dividing forms are seen in African trypanosomiasis, but not in American trypanosomiasis (Chagas' disease)

Winterbottoms sign

Ramana's sign: unilateral conjunctivitis and orbital edema 

Arboviral encephalitis

African Trypanosoma, trypanosomiasis

Togaviruses, Arboviruses

T. b. rhodesiense brucei gambiense

Mosquitoes(Culex)

Tsetse fly

Headache fever, coma

Decreased physical activity and mentalacuity

Immune serum Suramm; melarsoprol

Naegleria fowleri Protozoan

infects nasal mucosa from swimming water.

Figure 22.17

Naegleria fowleri Encephalitis caused by the protozoan

Naegleria fowleri is almost always fatal. Granulomatous amebic encephalitis,

caused by Acanthamoeba spp. and Balamuthia mandrillaris, is a chronic disease.

PROTOZOA FROM OTHER BODY SITES

FREE LIVING AMEBAE- Disease:

- Naegleria: Primary Amebic Meningoencephalitis (PAM)

- Acanthamoeba: Chronic Granulomatous Amebic Encephalitis and keratitis

- Lab Dx: Direct microscopic exam (Wheatley’s trichrome stain); culture of organism by inoculation of sample onto nonnutritive agar seeded w/ E. coli or E. aerogenes

FREE LIVING AMEBAE

- Portal of Entry: - Naegleria: nose- Acanthamoeba: respiratory tract or ulcers

in skin or mucosa / direct invasion of eye- Source of infection:

- Naegleria: warm lakes, streams, ponds or inadequately chlorinated swimming pools

- Acanthamoeba: immunocompromised or debilitated host

N. fowleri trophozoites cultured from cerebrospinal fluid: cells have characteristically large nuclei, with a large, dark staining karyosome.  The amebae are very active and extend and retract broad pseudopods. Trichrome stain. 

Naegleria spp.: trophozoite stained with Greenstein’s five dye stain And observed under dark field microscope.                                                                                                                                                 

PRIONS Diseases of the CNS that progress slowly and

cause spongiform degeneration are caused by prions.

Sheep scrapie and bovine spongiform encephalopathy (BSE) are examples of diseases caused by prions that are transferable from one animal to another.

Creutzfeldt-Jakob disease and kuru are human diseases similar to scrapie. They are transmitted between humans.

Prions are self-replicating proteins with no detectable nucleic acid.

Transmissible Spongiform Encephalopathies Caused by prions

Sheep scrapie Creutzfeldt-Jakob disease Kuru Bovine spongiform encephalopathy

Transmitted by ingestion or transplant or inherited.

Chronic and fatal

Transmissible Spongiform Encephalopathies

Figure 22.18

Classic CJD Variant CJD

Median age of death in years

68 (23-67) 28 (14-74)

Median duration of symptoms in months

4-5 13-14

Clinicalpresentation

Dementia, early neurologic sign

Prominent psychiatric and behavioral symptoms; delayed neurologic signs

Genotype Other amino acid combination

Methionine, methionin

Causative Agent

Susceptible Population

Transmission

Treatment

N. meningitidis

Children; military recruits

Respiratory

PenicillinCephalosporin

H. influenzae Children Respiratory

RifampinCephalosporin

S. pneumoniae

Children; elderly Respiratory

PenicillinCephalosporin

L. monocytogenes

Anyone Foodborne Penicillin

C. neoformans

Immunosuppressed individuals

Respiratory

Amphotericin B