Nyarango Dennis Level III

Case 1
A 22 yr. old man was complaining of a headache & said that light hurt his eyes. His Gp was called and observed that the ptnt was pyrexia & disorientated & that he had a stiff neck. A provisional diagnosis of Meningococcal meningitis was made. He gave the ptnt an injection of Benzylpeniccilin &arranged for his admission to hospital. On admission it was noted that the patient had dvp a petechial rush that did not blanch on pressure &that he was hypotensive.

Investigation
Blood was taken for culture & a full blood count As there was no evidence of papilloedema, a lumbar puncture was performed.

Lab results
Hematology: Hb 13g/dl; WBC 1810^9/l; polymorphs 80%; platelets 12010^9/l; Fibrinogen 1g/l Microbiology CSF: WBC 1000/cm3; polymorphs>90%; RBC 0-2/cm3; Proteins 0.6g/l; Glucose 2.0 mmol/l with blood glucose of 5.3 mmol/l

Cont.
Benzyl penicillin was continued whilst a waiting the result of microbiology. Gram negative intracellular diplococci were seen. Neisseria meningitides was grown from blood & CSF culture. Questions 1. Discuss briefly the etiology, risk factors &pathology of meningococcal meningitis, making a point to explain the dvp of each of the clinical symptoms and signs. 2. Discuss the laboratory findings in the patient. 3. What are the complication of meningitis?

Meningococcal meningitis
Meningococcal meningitis is an infection caused by a bacterium called Neisseria meningitides, which cause inflammation of the membranes covering the brain and spinal cord. Its primarily an early childhood infection but also affects adolescents & adults. Occurs World wide. Normally found in nasopharyx in about 5% of individuals and does not cause dx The leading cause of bacterial meningitis & septicemia

Neisseria meningitides.
Gram- negative, Oxidase positive, bean shaped diplococcus Has a polysaccharide capsule- antiphagocytic factor Occur intracellular in cytoplasm of neutrophils Strains are grouped into 12 serogroups on the basis of their polysaccharide capsule The most important are A,B,C,Y & W135

Diplococci.

Overview
The CNS is extremely resistant to infxns by bacterial pathogens due to protection by bony structures (skull & vertebral column), meninges & BBB. However once an infection has initiated, the CNS is susceptible to infxn than any other tissue due to inadequate defense mechanism preventing bacterial replication and progression.

Epidemiology.
1. Global dx distri.- Sub Sahara region meningitis belt. 2. Morbidity and mortality- High if un treated 3. Race predilection.- Slightly higher in African Americans than whites 4. Sex predilection.- Males accounts 55% 5. Age predilection. Affects individuals aged btn age 3yrs and adolescence. Rarely occurs in individuals aged 50yrs and above.

Risk Factors.
1. 2. 3. 4. 5. 6. Congenital complement deficiency. Dysfunctional Properdin component of the alternative pathway of complement. HIV infection. Functional or anatomic asplenia. Smoking and concurrent viral infection diminish the integrity of the respiratory mucosa and increase likelihood of invasive dx Crowding living conditions also facilitate disease spread, since individuals have diff strains of meningococcal.

Transmission
The bacteria enter the body is thru the upper resp tract. People can acquire the dx by inhaling the bacteria e.g. when an infected person coughs on them By direct mouth-to-mouth contact with an infected person By indirect contact e.g. by touching ones nose after touching an object or a hand that was recently contaminated with an infected persons nasal secretions

Pathophysiology
Many people are Nasopharyngeal carriers of Neisseria meningitides but few develop invasive dx. Factor associated with invasion include: viral infxn; dry dusty air; &passive smoking. Bacterial factors: Adhesion factors; IgA protease production; ciliary inhibiting factor; polysaccharide capsule; surface antigen. The polysaccharide of grp B meningococcal is non immunogenic because of its similarity to human neural cell adhesion molecule.


Host factor that limit survival of meningococcal: innate immunity and acquired immunity-specific antibodies. Deficiency in terminal composed of complement pathway &properdin def.- both lead to recurrent infxn Mutation in the mannose binding lectin gene increased the risk of Meningococcal dx.

Pathogenesis
Bacteria invade the CNS by haematogenous spread and the upper resp tract is the common source of entry Meningitis is initiated when the bacteria colonize the mucosa of the nasopharynx and invade the blood stream thru the epithelial cells In the blood stream, the bacteria replicate and survive the hosts defenses and gain access to the CNS directly thru the microvasculature or the porous choroid plexus


Cross BBB & survive & multiply in CSF. Once in CSF, bacterial multiplication is facilitated as the CSF lacks several host defenses including low levels of Ig & complement The hosts immune status &bacterial virulence factors will play a role in establishment of the infxn

Pathology
When bacteria die, lipids & oligosaccharides, including endotoxin, are released from their walls. Some of the components cause vascular injury & shock. Symptoms of sepsis may develop & even death from gram- negative shock, before inflammation occurs. Bacterial cell wall components also induce meningeal macrophages, Astrocytes & microglial cells to produce IL1,TNF- & other inflammatory mediators. These cytokine attract circulating granulocytes and monocytes into csf


As they lyse, granulocytes & monocytes release powerful lysosomal enzymes &free radicals which destroy neural tissue &damage blood vessels. Polyunsaturated fatty acid released from the membranes of dying neutrophils also cause increased vascular permeability The results of vascular permeability(cerebral edema) &vasculitis (ischemia) Results of inflammation are tissue & vascular injury & increased intracranial pressure.

Gross & Microscopic findings

In the acute phase of the dx, purulent exudate are seen grossly within the sub arachnoid space Marked congestion of the leptomeningeal vessels & cerebral edema is prominent. Microscopic- Abundant cellular infiltrates on meninges composed of neutrophils accompanied by fibrin exudate Intracellular or Extracellular bacterial may be seen.

Pus in subarachnoid space.

Inflammatory cells in subarachnoid space.

What is the course of the disease?

Usually has 3 main stages. 1. Bacterium multiply in nasal passages & throat causing no pain. 2. Invade the blood, introduce toxic substances into the circulation and causing fever, rash appears & develop hemorrhage spots( petechia & purpura) in severe cases. 3. Bacteria multiply in the meninges, where they produce intense inflammatory changes & an exudate of pus

Purpura rash

Characteristics of meningitis

Rapid onset of symptoms. First symptom is usually vomiting, a severe bursting headache develops when meninges have become inflamed and the increase of CSF pressure. Stiff neck develops owing to irritation of spinal nerves supplying those muscles Deep tendon reflexes are exaggerated &convulsion may occur Photophobia is due to meningeal inflammation and increased intracranial pressure.

Laboratory results
Total Blood count, The WBC are increased due to presence of the bacterial infection in blood(meningococcemia) and decrease in fibrinogen, due to loose of proteins in circulation into CSF and being used up during micro thrombi formation. Marked elevated CSF protein due to break down of the BBB Low glucose levels (<45mg/dl ratio of serum: CSF glucose< 0.4) Consumed by inflammatory cells Increased WBC more than 100fold with polymorphs predominating.

Complications
Hypoxic ischaemic encephalopathy due to shock Neurological deficit due to increased intracranial pressure Toxic metabolic encephalopathy due to diffusible substances e.g. cytokines- have neurotoxic action Hydrocephalus due to purulent CSF obstruction and leptomeningeal fibrosis- impairs reabsorption. Hearing loss due to extension of infection of cranial nerves- auditory nerve

Hydrocephalus meningitis complication

Vascular narrowing in meningitis

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