Bacterial Meningitis: Neisseria

Protection of CNS

• The brain is surrounded by meninges
• Meninges consist of the dura mater, arachnoid mater, and pia mater
• The subarachnoid space contains cerebrospinal fluid (CSF)
• The blood-brain barrier restricts the permeability of blood vessels in the brain
• The blood-brain barrier keeps microbes out, but makes it difficult to introduce drugs

Meningitis, Encephalitis, and Meningoencephalitis

• Meningitis involves the meninges
• Encephalitis involves the brain
• Meningoencephalitis involves both

Bacterial Meningitis: Neisseria

• A sample of CSF can be tested
• Gram stains and cultures can be performed
• Symptoms include light sensitivity, fever, sore neck, and severe headache
• The bacterium is Neisseria meningitidis meningococcus
• Transmission occurs through droplet contact
• An endotoxin stimulates WBCs
• Cytokine release damages blood vessels, leading to vascular collapse
• 25% of all meningitis cases are related to this bacterium
• A conjugate vaccine exists

Streptococcus Pneumoniae

• Streptococcus pneumoniae can cause meningitis of pneumonia or pneumonia itself
• Transmission occurs through droplet contact
• Capsules resist phagocytes
• Vancomycin can be used as treatment
• Prevnar and Pneumovax are vaccines

Coccidioides Immitis

• Coccidioides immitis has two forms and grows at 25°C and 37°C
• Coccidioides immitis is a true infection
• Ranges from mild respiratory to meningitis
• Coccidioides immitis causes "valley fever" found in the SW US and Mexico

Amebic Meningoencephalitis

• Protozoans are found in recreational fresh water
• Amebic Meningoencephalitis is rare, but usually fatal
• Naegleria fowleri causes primary amebic meningoencephalitis (PAM)
• Naegleria fowleri enters through the nasal passage
• Acanthamoeba granulomatosa causes amebic encephalitis (GAE)
• It enters through broken skin

Toxoplasmosis

• Toxoplasma gondii is a protozoan parasite
• Animals are reservoirs (domestic and wild)
• Transmission through contact with soil and protozoa
• Humans are infected through contact with cats (or animal feces)
• Pregnant women can be infected and damage the fetus (hydrocephalus)

Prion Infections

• Prion infections are caused by abnormally folded, infectious proteins
• Prions are resistant to most heat and chemical treatments
• They cause transmissible spongiform encephalopathies
• They are neurodegenerative diseases with long incubation periods
• Creutzfeldt-Jakob Disease (CJD) is an example

Bacterial Meningitis: Hemophilus Influenzae

• Hemophilus Influenzae is transmitted through droplet contact
• Humans are the only reservoir
• Hib is serotype B, leading to the Hib vaccine
• A subunit vaccine has been available since 2 months old + booster 1985 and is now virtually eliminated in the US

Listeria Monocytogenes

• Listeria Monocytogenes are G+ rod-shaped bacteria
• The disease is Listeriosis
• Healthy adults experience mild infection with fever, diarrhea, and sore throat
• Immunocompromised individuals can experience meningoencephalitis and septicemia
• Pregnant women can transmit it across the placenta to the fetus
• It is found in contaminated dairy products, poultry, and meat

Fungal Diseases: Cryptococcus Neoformans

• Cryptococcus neoformans can cause meningoencephalitis
• The meningitis is a chronic disease and opportunistic infection
• Cryptococcus neoformans has large, thick capsules
• Found commonly in bird droppings where the inhalation of dried droppings happens
• It is prevalent in AIDS patients

Rabies

• Rabies is caused by a ssRNA virus (bullet-like)
• Rabies has a long incubation period (1-2 months)
• It progresses to fatal encephalitis
• Post-exposure vaccination is available

Polio (Poliomyelitis)

• Poliovirus is an RNA virus
• Most cases are mild 1% can cause paralysis
• Virus multiplies in throat and intestines through ingestion
• The virus can penetrate the CNS and infect nerve cells

Polio Vaccines

• There are two types of polio vaccines
• Salk vaccine (1955): inactivated polio vaccine, multiple injections
• Sabin vaccine (1963): live attenuated, oral; cheaper and easier to administer, excellent long-life immunity; danger, can revert to active virus

Tetanus

• Tetanus causes spastic paralysis
• Clostridium tetani is the causative agent.
• Clostridium tetani is G+ rod and obligate anaerobe
• It is common in soil (endospores)
• A potent neurotoxin tetanospasmin (exotoxin) is produced
• Death occurs due to spasms in respiratory muscles
• A DTaP vaccine exists

Botulism

• Botulism causes flaccid paralysis
• Clostridium botulinum is the causative agent
• Clostridium botulinum is G+ rod and an obligate anaerobe
• Endospores, soil, exotoxin
• It can cause food poisoning, infant botulism in honey
• Hypotonia (floppy baby syndrome) causes loss of muscle control
• In cosmetics, it paralyzes facial muscles

Protozoan Diseases: African Sleeping Sickness (Trypanosoma brucei)

• African Sleeping Sickness is also known as Trypanosomiasis
• T.b. gambiense accounts for 95% of cases
• T.b. rhodesiense accounts for 5% of cases
• It is spread by the tsetse fly, only in Sub-Saharan Africa
• Treatments include suramin and pentamidine (prior to CNS involvement)
• Melarsoprol (arsenic based) Eflornithine (parasitic protein inhibition): treatment after crossing the blood brain barrier
• Melarsoprol is highly toxic
• Eflornithine is costly and requires several injections

Anatomical Defenses

• Anatomical defenses include Nasal hairs
• Ciliary escalator with Ciliated epithelial cells of trachea
• Mucus
• Coughing, sneezing, and swallowing

Microbiota

• A large number of commensal organisms can act as microbes
• Important for microbial antagonism

Infections of the URT

• The Common Cold is an infection of the Upper Respiratory Tract
• 200 different viruses can cause it
• Rhinovirus, Coronavirus, and Adenovirus are example viruses
• Common cold can cause sneezing, congestion, and a runny nose
• Transmission through droplet contact
• Symptoms can be treated

Sinusitis

• Sinusitis involves an inflammation of sinuses
• Sinusitis can cause sinus pain, nasal congestion, pressure, headache, or toothache
• Discharge can have a yellow/green color
• Caused by allergens, viruses, and bacteria
• Patients suffering from a common cold often develop sinusitis

Infections of U+LRT: Whooping Cough (Pertussis)

• Bordetella pertussis is the causative agent
• Bordetella pertussis is a G- Coccobacilli bacterium
• Has three phases
• Catarrhal phase: bacteria in the resp tract cause cold symptoms
• Paroxysmal Phase: uncontrollable coughing (whoop sound)
  • Broken blood vessels in eyes, vomiting
• Convalescent phase: Bacteria decreasing, ciliated epithelia damage
• Recovery takes weeks to months, likely to be reinfected
• DTaP vaccine exists

Influenza

• Influenza is a segmented ssRNA virus
• Symptoms: chills, fever, headache, muscle aches
• Hemagglutinin binds host cell receptor
• Neuraminidase causes viral budding & releasing
• 1918 Spanish Flu was an influenza pandemic
• 2009 Swine Flu was an influenza pandemic
• There are 3 different inactivated strains of vaccines, updated annually

Mutations

• Antigenic Drift: Small genetic changes that reduce IR
• Antigenic Shift: Major genetic changes, swapping of RNA segments between influenzas

Otitis Media (Ear Infection)

• Otitis media is an infection of the eustachian tubes causing inflammation and fluid build-up
• Eardrum bulges
• Kids are more susceptible because they have narrower tubes

Pharyngitis (Strep Throat)

• Pharyngitis is an inflammation of the throat causing pain and swelling
• Difficulty swallowing
• Viral pharyngitis results in mild symptoms and hoarseness
• Bacterial pharyngitis is more painful and often accompanied by fever, headache, and nausea

Diphtheria

• Diphtheria is caused by Corynebacterium diphtheriae
• Corynebacterium diphtheriae is G+ club shaped
• A pseudomembrane blocks airway
• Exotoxin (phage encoded)
• Vaccine: diphtheria toxoid (part of DTaP vaccine) includes diphtheria, tetanus, pertussis toxins
• Toxin is converted to toxoid
• Toxin modification is done by modifying, weakened toxin
• Antigenic determinants are present

Infections of Lower Respiratory Tract (LRT): TB

• TB caused by Mycobacterium tuberculosis
• Mycobacterium tuberculosis is an acid-fast rod
• Mycolic acids stimulate inflammatory response causing low infectious dose
• Primary TB: Infectious dose of 10 bacteria
• Tubercles: granulomas containing TB bacteria and enlarged macrophages
• Secondary (Reactivation) TB: Remains dormant in lungs and reactivates when immunity wanes
• Severe symptoms: violent coughing, greenish or bloody sputum, chest pain, weight loss
• Extrapulmonary TB: outside of lungs
• Diagnosis: Mantoux Test: inject TB antigens, presence of swelling test for prior exposure
• Can also diagnose with a sputum culture or chest X-ray to determine active TB
• treatment :multiple drugs for 6-9 months
• Patient non-compliance leads to drug-resistant strain
• MDR-TB is multi-drug resistant TB

Infections of LRT :Pneumonia

• Pneumonia consists of multiple diseases
• Pneumonia is an inflammatory condition of the lungs where fluid fills alveoli
• Pneumonia can cause congestion, headache, fever, chest pain, cough, discolored sputum, difficulty breathing
• Community-acquired pneumonia: Streptococcus pneumoniae (40%) , viruses (30%), mycoplasm (20%) or walking pneumonia, 10% is other organisms
• Legionella (bacteria)
• Hemophilus influenzae (bacteria)
• Histoplasma capsulatum (fungus)
• Hantavirus (virus)
• Healthcare-associated pneumonia: ~ 1% of patients develop pneumonia
• Associated with mechanical ventilation
• 30%-50% mortality rate
• Most cases are polymicrobial: Pseudomonas aeruginosa, Strep. pne., Klebsiella pne.
• Pneumonia is treated with broad-spectrum antibiotics