CNS infections

Question 1

What are the types of CNS infections

Answer 1

Blood-borne infections

• Blood-brain barrier –> encephalitis (brain tissue infection)
• Blood CSF (cerebrospinal fluid) –> meningitis (coverings infection)

Viral infections - aseptic meningitis

• Increase in T cells, monocytes, CSF remains clear

Bacteria infections - septic meningitis

• rapid increase in polymorphs and protein, CSF turbid

Question 2

Define encephailitis and meningitis

Answer 2

encephailitis: inflammation of the brain

• Most often from viruses
• Common clincial features –> abnormal behaviour, seizures, nausea, vomiting fever

meningitis​: infection of the meninges, the membranes that surround the spinal cord

• Viral is less severe than bacterial

Question 3

What are the bacterial infections for meningitis?

Answer 3

Non-viral meningitis –> more severe (less common thnan viral meningitis)

• After introduction to Hib vaccine, N.meningitidis and S.pneumoniae are now responsible for the majority of bacterial meningitis are now responsible
• Spread through coughing or sneezing or close contact with infected people

Question 4

What is N.meningtidis? Describe its microbe features, transmission, clinical fatures and transmission

Answer 4

Neisseria meningitidis – Gram-negative, diplococcus, polysaccharide capsule (serotypes, O antigen)

Transmission- through person-person, outbreaks in crowded environments (prisons, dorms)

• Through droplets, facilitated by other respiratory infections
• If children lost antibiodies from mother –> infection more frequent

Pathogenesis: Pili attach to epithelium in naspoharynx, invasion of blood and meninges poorly understood, capsule avoids phagocytosis and complement attachment

Serotypes: 13 serovars worldwide

• Developed countries - B, C and Y predominate
• Developing countries - A and W-135 more common
• Incubation period 1-3 days

Signs and symptoms:

• onset features: sudeen, sore throat, headache, drowsiness
• signs of meningitis: fever, irritability, neck stiffness photophobia
• Bleeding in brain and adrenal glands if severe

Treatment

• Mortality is 100% if untreated, ~10% if treated
• Diagnosis – through microscopic examination of CFS, white blood cell count and Gram stain for rapid diagnosis, followed by culture
• Immediate administration of antibiotics: penicillin, ampicillin,
• Vaccines for major serotypes

Question 5

What is H.influenzae? Describe its microbe features, transmission, clinical fatures and transmission

Answer 5

• Gram-negative coccobacillus (normal urt flora)
• Capsular (typeable) and non-capsular strains (non-typeable)
• Six encapsulated serotypes based on distinct capsular polysaccharides (a-f)
• H. influenzae type b (Hib) is by far the most common serious disease causing strain

H.influenzae pathogenesis

• The type b polysaccharide capsule (Hib) is the major virulence factor

> Encapsulated organisms can penetrate the epithelium of the nasopharynx and invade the blood.

> Capsule gives resistance to phagocytosis and complement mediated lysis

• Capsule composition is polyribosyl ribitol phosphate (PRP)

> PRP is the vaccine antigens

• Hib does not produce exotoxins
• Endotoxin (LPS) mayt play a role in systemic disease

H.Influenzae Clinical Features

• Bacteraemia – systemic blood infection
• Meningitis – CNS infection of meninges
• Epiglottitis - inflammation of the windpipe - obstructive

> Non-typeable –> oppurtunistic infections: no capsule

• Incubation period for meningitis ~5-6 days
• Meningitis is the most common
• Risk factors - socioeconomic status and ethinicity -> historically higher rates in indigenous children

HiB treatment and vaccine

• Diagnostic features as for meningococcal meningitis •
• General treatment features as for meningococcal meningitis
• Clinical management – hospitalisation and antibiotic therapy
• Hib disease is not common over 5 years age even in unimmunised individuals
• Immunity to Hib polysaccharide capsule (PRP) is protective
• Vaccine: Infanrix hexa:diphtheria, tetanus, pertussis (whooping cough), hepatitis B, poliomyelitis (polio) and Hib

Question 6

What is S.pneumoniae –> causes pneumococcal meningitis Describe its microbe features, transmission, clinical fatures and transmission

Answer 6

Geam Positive coccus (capsular)

• Remains a major cause of morbidity and mortality
• Common normal throat flora in healthy individual
• Infections of blood and meninges is rare (more common in <2 yrs and elderly)

Clinical features: as for meningococcal infections but generally more severe, 20-23% mortality, 15-20 morbidity

Pneumococcal Treatment and Vaccine

Treatment – penicillin, but resistance has been seen → combination therapy​

• Vaccine: prevenar 13 (a 13-valent pneumococcal polysaccharide conjuagate vaccine) –> against 13 serotypes
• 2,4,6 months of age

Question 7

What is HSV ecephalitis? What is it pathology?

Answer 7

Herpes simplex virus, most common types of sporadic encephalitis

• Neonates – acquire HSV-2 through birth canal (gential warts)
• Older children and adults – HSV-1 – (cold sores) due to virus reactivation in neurons, travels to temporal lobe of brain
• Diagnosis – CT and MRI cans showing temporal lobe enlargement
• Untreated has 70% mortality
• Treatment with Acyclovir

Pathology

• Viruses localizes in blood vessel
• Virus leves blood vessel
• T cell sensitized to virus or host component to release cytokines
• Cytokines induce infiltration of mononuclear cells (antibody production)
• Virus infects neural cells
• Further viral spread –> destruction of infected neural cell
• Infection finally controlled but causes immunopathology

Question 8

What is the poliovirus? What are the virus features, transmission, clinical features and treatment and prevention, VAPP

Family: Picornaviridae; Genus: Enterovirus

Answer 8

• ssRNA genome, non-enveloped
• Disease poliomyelitis
• Major cause of sporadic encephalitis
• In 1916 epidemic in New York
• 9000 cases most <5 years, <1% mortality
• Enteroviruses are transient inhabitants of the gastrointestinal tract - stable at acid pH
• Transmitted through faecal-oral route
• Three poliovirus serotypes (P1, P2, and P3)
• Immunity to one serotype is not protective against the other serotypes

Infection and Pathogenesis

• Finding a victim (virus enters body thtough contaminated food, dirty fingers or water tainted with sewage)
• Virus attaches to receptor on intestinal walls (oral polio vaccines attaches to the same ones) –> gets into bloodstream
• Even in people with no symptoms, virus is exreted in faeces that can contaminate food and water
• Nerve cell death can cause paralysis mostly in the legs
• In less than 0.5 % of cases, the virus attacks the central nervous system, destroying cells in the spinal cord

Clinical Features

• Incubation period 6-20 days
• 95% infections are asymptomatic
• <1% infections result in flaccid paralysis
• Many patients recover compeltely and muscle function returns to some degreee
• Wakness or paralysis still present 12 months afer onset is usually permanent
• Mortality 2-5 %

Polio Vaccine

1955 - Inactivated polio vaccine (IPV)

• Contains 3 serotypes of vaccine virus
• Effective protection against CNS infection
• May still permit GI tract infection –> Symptomless carriage is possible

1963 - Oral Polio Vaccine (OPV)

• Contains 3 serotypes of vaccine virus
• Live attenuated virus strains
• Immunity against replication is GI Tract and CNS infection
• Shed in stool for up to 6 weeks following vaccination

1987 - Enhanced-potency IPV (EPV)

Global Polio eradication initiative

• Eradicate polio by 2000, setbacks (war, framnine)

VAPP -Vaccine Associated Paralytic Polio

• Compliction of oral polio vaccine
• Likely due to mutation of the OPV strain to a more virulent strain before immunity is acquired
• Very low risk - Estimated at 1 per 2.5 million vaccinations
• Give IPV first then OPV to reduce incidence
• IPV is now used –> oral polio vaccine no longer used

Question 9

What is the rabies virus - Rhabdovirus. What is its causative agent, its features, transmission, clinical features, treatment and prevention

Answer 9

• Rabies is caused by the Lyssavirus, part of the Rhabdoviridae family, bullet-shaped ssRNA

7 genotypes: genotype 1 is world-wide, genotype 7 is the Australian bat Lyssavirus

• Present in 150 countries: Australia is among several other island countries free of rabies
• Most warm-blooded animals can be infected
• Dog bits responsible for 99% of human infections
• Pathogenesis - Virus travels from bite along neurons to CNS, causes encephalitis, then infects other cells
• 4-13 week incubation time – the further the bite is away from brain the longer it takes.

Clinical Features: sore throat, headache, fever, patient becomes excited with muscle spasms, difficulty sawllowing

• Once symptoms have been developed its fatal, due to cardiac/respiratory arrest within a few days

Treatment: the sooner treatment is started after bit the better, prevents onset of disease

• Wounds should be thoroughly cleaned
• Passive immunisation – human rabies immunoglobulin (HRIG) administered at site of bite
• Post-exposure prophylaxis – three doses of vaccine in 1 month; very effective at stopping virus due to very slow incubation time
• Vaccination – recommended for travellers to endemic areas. Two available in Australia (inactivated): Mérieux, Rabipur

Question 10

What is Tetanus? What is their causative agent, infection route, clinial features and treatment

Answer 10

Clostridium tetani produce neurotoxins that caused damage to CNS – extremely potent at low doses

Tetanus = caused by C.tetani

• Gram-positive, bacillus, anaerobic, spore-forming
• Usually spores are deposited in cuts from soil, contamination by animal faeces
• Bacteria proliferate in anaerobic infection conditions → Tetanospasmin
• Toxin carried in peripheral nerve axon, and probably in blood, to CNS
• Blocks release of inhibitory neurotransmitters on neurons
• –> Over-activation of motor neurons

Clinical Features

• Muscle rigidity and spasms, ~3-21 days after infection
• May lead to respiratory failure and death, ~ 50% mortality
• Note – bacterial are rarely isolated from infection site, only
• need a small number to produce enough toxin for disease
• Therefore diagnosis is usually clinical

Treatment

• Penicillin to stop bacterial replication
• Anti-tetanus immunoglobulin (passive immunity) if clinical signs severe
• Muscle relaxants and respiratory support
• Ifranrix Hexa vaccine = Last 10 years

Question 11

What is Botulism? What is their causative agent, infection route, clinial features and treatment

Answer 11

Clostridium botulinum produce neurotoxins that caused damage to CNS – extremely potent at low doses

Botulism = caused by C.botulinum

• Gram-positive, bacillus, anaerobic, spore-forming
• Spores in the environment e.g. vegetables, meat, fish can contaminate improperly cooked and preserved foods
• Spores can also contaminate wounds or be ingested
• If preformed toxin is ingested – absorbed through gut into blood → acts on synapses

​> Blocks acetylcholine release

>Affects muscle and autonomic nervous system

Clinical Features

• After 2-72 hours
• Increasing weakness and paralysis, discomfort swallowing, vomiting, double vision, muscle failure

Treatment

• Trivalent antitoxin = respiratory support
• Mortality <20%