1. Bacterial Meningitis
Linnea Giovanelli

2. What Is Meningitis?
The three layers of the meninges
Bacteria can reach the meninges through the bloodstream or direct contact
Inflammation of the meninges through bacterial spread in cerebrospinal fluid, CSF
--Inflammatory host response to infection – the strong the inflammatory response, the more damage caused.
--Little control of infection can occur in CSF because of low immune system response
Direct contact of meninges occurs through severe head injuries or ear/nose infections and sometimes just randomly.
Bloodstream infection – bacteria from another injury on body enter and travel through bloodstream

3. Bacterial Infection – Why Meningitis Is Difficult
Many species of bacteria can cause bacterial meningitis
Neisseria meningitidis
Haemophilus influenzae
Streptococcus pnemoniae
Listeria monocytogenes
FIVE TYPES - Bacterial, viral, parasitic, fungal, non-infectious (CDC)
Strep – most common cause in adults; NM – most common in children (since advent of HiB vaccine) and 2nd most common in adults
FOCUS on N. meningitidis because it is the only one that causes epidemic meningitis

4. Different Ages Have Different Risks
Newborns
Group B Streptococcus (GBS), E. coli, L. monocytogenes
Infants and Children
S. pneumoniae, N. meningitidis, H. influenzae type b
Adolescents and Young Adults
N. meningitidis, S. pneumoniae
Older Adults
S. pneumoniae, N. meningitidis, L. monocytogenes
Newborns – highest risk. Vertical infection of GBS from mother

5. Transmission and Incubation
Bacteria is largely carried in the nose and throat of humans
Most people carry these colonies
Bacteria are about as contagious as the flu or common cold
L. monocytogenes is spread through contaminated food
Incubation usually lasts about four days but can be as long as ten
Meningococcal disease =/= meningitis – any disease caused by N. menin. is meningococcal disease, but not all these diseases are meningitis
N. meningitidis is spread through respiratory/throat secretions

6. Nesseria meningitidis
Gram negative anaerobe
Iron reduction is a necessary part of metabolism
12 total serogroups
Types A, B, C, Y and W135
Specific capsular proteins
A and B are most pathogenic
--Group B is the leading cause of endemic meningitis in industrialized countries – 30-40% of cases in US and up to 80% in Europe
--Group A causes large scale epidemics in developing countries, especially the sub-Saharan Africa “meningitis belt”
--does not exist outside humans because iron intake is dependent on human iron compounds
CSF culture of N. meningitidis

7. N. meningitidis Antiphagocytic polysaccharide capsule
Lives and replicates inside cytoplasm of neutrophils
Major toxin is lipooligosaccharide, LOS
LOS has been shown to suppress leukotriene B4 synthesis
CAPSULE – most important virulence factor
--Capsular proteins provide an important targeting factor for the immune system
--LOS = highly lethal when purified in lab; very potent endotoxin and major component of bacterial cell wall
--Endotoxin – toxic factor that is only released when cell wall is destroyed
--B4 – a chemokinetic and chemotactic factor important in leukocytes

8. SYMPTOMS Untreated or late-stage: Always exhibit: Seizures Coma
Fever
Headache
Neck stiffness
And may exhibit one or more of the following:
Altered mental state
Nausea, vomiting
Photophobia
Untreated or late-stage:
Seizures
Coma
Death
--Can be chronic (one month or more), acute (rapid onset – 80% of cases) or mild/aseptic
--Brain does swell and bleed in advanced cases
--N MEN – characteristic purple/red skin rash

9. Diagnosis and Treatment

10. Mortality Rate Dropped Sharply With Use of Antibiotics
Sulphonamide resistance – 1960s, N. meningitidis
Penicillin resistance – 1990s, pnemoccocal
Ampicillin resistance – 1970s, H. influenzae
Death rates dropped dramatically in the 1940s due to the introduction of sulfonamides
- Further drug development led to successful treatment with penicillin, ampicillin, vancomycin and cephalosporins
Resistance?
- In the US, resistance to the three early drugs – sulphonamide, penicillin and ampicillin arose as early as the 1960s

11. In the Developed World…
Current US case rates between
Streptoccocus pneumoniae remains the leading cause of death
Risk has decreased for children, but the rates of infection in infants under 2 months has remained the same
WHO estimates that bacterial meningitis causes around 170,000 deaths/year worldwide
An estimated 4,100 cases, with roughly 500 deaths occurred each year in US
– of the deaths observed in , 70% were from S. pneumoniae
Death occurs in 10/11% of cases

12. 800,000 cases in last 15 years –
10% resulted in deaths, 10-20% survived with neurological defects
--Large outbreaks have occurred in Asia, and smaller ones in Europe + US in the past 30 years but most large-scale outbreaks occur in Africa.
--Epidemics cycle in Africa and large outbreaks generally occur in the dry season
(WHO)

13. Diagnostic Methods Clinical Analysis Laboratory Analysis
Patient presents with typical symptoms – bacterial meningitis is suspected when other causatives are ruled out
Laboratory Analysis
Lumbar puncture to produce cerebrospinal fluid, CSF
Gram stain of CSF
Culture of CSF
Identification of bacterial antigen
-OTHER CAUSATIVES: TB, viral infections
--Controversy over start of antibiotics courses – at clinical diagnosis or at laboratory?

14. Treatment procedures depend on causative bacteria
Correct diagnosis of causative bacteria is essential. Though any of the above procedures will most likely eliminate all of the bacteria, there is the potential for resistance emerging when the optimal combination is not used.
Tunkel, A.R; Practice Guidelines for the Management of Bacterial Meningitis

15. Cephalosporins – 3rd Generation
β-lactam antibiotics
Derived from fungus Acremonium
Similar in structure and action to penicillin
Each generation has increasing activity against Gram negative bacteria and decreasing activity against Gram positive
Acremonium (previously called Cephalosporium)
Acremonium (cultured)

16. β-Lactam
Core of several antibiotics like penicillin and cephalosporins
Attack peptioglycans in bacterial cell walls
Inhibition of cell wall synthesis
Resistance forms when bacteria develop β-lactamase
Microbiology: A Human Perspective, Nester 7th edition
--The chemical structure of cephalosporins make them resistant to inactivation by some beta-lactamases
--inhibit cell wall synthesis leading to cell lysis
--extended spectrum lactamase = higher resistance
--R group variation

17. Resistance
Pneumococcal meningitis has shown increasing rates of penicillin resistance
Mildly resistant strains to other popular drugs are emerging
Cephalosporin resistance is not common
R groups can be changed – many variations

18. Vaccinations - Meningococcal
Active against types A, C, Y and W-135
Two vaccines available in the US, a polysaccharide and a conjugate
Conjugate vaccine
Strongly recommended for years old
Boosters needed after five years
85-100% effective
No vaccine for type B
Important to note that they are NOT active against subgroup B – cause of roughly 1/3 all cases in the US. Vaccine is fractional and contains only a part of the microbe – aka it will not infect you.
--No B because components of the polysaccharide coat have similarity to components in human neurological tissues --

19. Vaccinations
Pnemoccocal vaccines also have two types – conjugate, PCV13 and polysaccharide, PPVSV
HiB Vaccine
Recommended for all children under 5
Pnemoccocal also has few side effects
Pics:

20. Vaccinations in the Developing World
Vaccination clinic
International Coordinating Group (ICG)on Vaccine Provision for Epidemic Meningitis Control
Established in 1997
Coordinate meningitis vaccine distribution
--Get vaccines where needed most, avoid wastage
--Composed of Doctors w/o Borders, Red Cross, UNICEF and WHO
--Created largely for prevention/amelioration of outbreaks in Africa, it is available to any country facing potential epidemic
WHO – developed and currently working on spreading and approving access to their vaccine specifically for Type A in the highest risk countries

22. References http://www.nlm.nih.gov/medlineplus/ency/article/000680.htm
Nester, E.; Anderson, D.; Roberts, C.E.; Microbiology: A Human Perspective. McGraw Hill Higher Education, 7th ed., 2012.
Hameed, N.; Tunkel, A. R.; Curr. Infect. Dis. Rep. 2010, 12, 274. (Treatment of Drug-resistant Pneumococcal Meningitis)
Gold, R.; Infect. Dis. Clin. North Am. 1999, 13, 515. (Epidemiology of bacterial meningitis)
Swartz, M. N.; N. Eng. J. Med. 2004, 351, (Bacterial Meningitis – A View of the Past 90 Years)
Ginsberg, L. J. Neurol. Neurosurg. Psychiatry 2004, 75. (Difficult and Recurrent Meningitis)
Tunkel, A. R.; Hartman, B. J.; Sheldon, L. K.; et al. Clin. Infect. Dis. 2004, 39, (Practice Guidelines for the Management of Bacterial Meningitis)
Thiqpen, M. C.; Whitney, C. G.; Messonnier, N. E.; Zell, E. R.; et al. N. Engl. J. Med , 26, (Bacterial Meningitis in the United States, )