Meningitis

University of Baghdad – College of medicine
SSC Module
( Student Selected Component )
Neuroscience module (NS)
Meningitis
Prepared By
Mustafa Abd-Alamam
Second grade
‫الطالب‬
‫عبدالسادة‬ ‫اليذ‬ ‫عبداالمام‬ ‫مصطفى‬
‫بغداد‬ ‫جامعة‬ / ‫الطب‬ ‫كلية‬ / ‫الثانية‬ ‫المرحلة‬
2018-2019

1
List of contents Page
1 Objectives of study 2
2 introduction 3
3 Etiology of meningitis 4
4 Symptoms of meningitis 7
5 Diagnosis of meningitis 9
6 Management of meningitis 13
7 Prevention 17
8 Epidemiology of meningitis 20
9 History of meningitis 22
10 Summary 23
11 References 24
List of tables Page
Table 1 9
Table2 12
Table3 14

2
Objectives of study :
1- To get general cognition about meninges and .
2- To relate the causes of meningitis .
3- Knowledge How to identify the patient with meningitis .
4- To list the diagnostic procedures and investigation of this disease.
5- To know about the modern therapeutic method of meningitis .
6- As the meningitis is life-threating case , how to manipulate the
meningitis , especial with bacterial meningitis in child .
7- To clarify the importance of the vaccine in decline of meningitis around
the world.
8- To learn about the distribution of meningitis among the population and
countries .
9- In short, how the history of meningitis developed over the years .

3
Introduction
The meninges refer to the membranous coverings of the brain and spinal cord.
There are three layers of meninges, known as the dura, arachnoid and pia mater.
Main function of these layers and the cerebrospinal fluid is to protect the
central nervous system.
The meninges are often involved cerebral pathology, as a common site of
infection (meningitis), and intracranial bleeds.
The dura mater is the outermost layer of the meninges, lying directly underneath
the bones of the skull and vertebral column. It is thick, tough and inextensible.
The arachnoid mater is the middle layer of the meninges, lying directly
underneath the dura mater. It consists of layers of connective tissue, is avascular,
and does not receive any innervation.
The pia mater is located underneath the sub-arachnoid space. It is very thin, and
tightly adhered to the surface of the brain and spinal cord.
It is the only covering to follow the contours of the brain (the gyri and fissures), it
is highly vascularized .
Meningitis is a rare infection that affects the meninges that cover the brain and
spinal cord.
There are several types of this disease, including bacterial, viral, and fungal.
Bacterial meningitis can be life-threatening and spreads between people in close
contact with each other.
Viral meningitis tends to be less severe, and most people recover completely
without treatment.
Fungal meningitis is a rare form of the disease. It usually only happens in people
who have a weakened immune system .

4
Etiology of meningitis :
1. Bacterial meningitis : when bacteria get into the bloodstream from the sinuses,
ears, or throat. The bacteria then travel through the bloodstream to the brain
.Bacterial meningitis is very serious and can be deadly. Death can occur in as little
as a few hours.
The bacterial meningitis differ among age group ( e.g. Neisseria meningitis isn't
affect the newborn but more than 1 year can be vital cause )
• Neisseria meningitidis, often referred to as 'meningococcus', is a Gram-
negative bacterium that can cause meningitis , was identified in 1887
,Twelve subtypes or serogroups of N. meningitidis have been identified and
four (N. meningitidis, A, B, C and W135) are recognized
to cause epidemics.
• Haemophilus influenzae type b. : gram-negative bacteria , this was the main
form of meningitis in young children in the UK until 1992 . transmit by
throat and nose .
• listeria monocytogenes meningitis : It is a facultative anaerobic gram-positive
bacterium , cause 'Listeriosis' is the third most frequent cause of bacterial
meningitis. It is principally spread by contaminated food, which was
discovered after outbreaks of listeriosis in the 1980s
• Group B Streptococcus : the biggest cause of neonatal meningitis (meningitis
in newborn babies) in the UK and Ireland.

5
• Streptococcus pneumoniae (S. pneumoniae) : is a gram -positive bacteria
causes meningitis, pneumonia, and sinus infections. pneumoniae is the
most common cause of bacterial meningitis in adults. It is also among the
leading causes of bacterial meningitis in children under 2 years old
On average, bacterial meningitis caused about 4,100 cases and 500 deaths in the United
States each year between 2003 and 2007. (1)
2. Viral meningitis (aseptic meningitis): is more common than bacterial
meningitis, and usually less severe.
Most cases of viral meningitis are caused by enteroviruses, but other common
viruses such as measles, mumps, and chicken pox, as well as some viruses spread
through mosquitos or other insects, can also lead to the disease.
Viral meningitis has the same types of symptoms as bacterial meningitis,
including sudden fever, headache, and stiff neck, but it’s different in that it’s
aseptic, meaning bacteria will not grow in the cerebrospinal fluid. It often resolves
on its own, without specific treatment, although it may be treated with antiviral
medication.

6
In some cases, it can be fatal, depending on factors such as the type of virus
causing the infection, the patient’s age, and whether he or she has a weakened
immune system
3. Fungal meningitis: is rare and usually caused by fungus spreading through blood
to the spinal cord, It not contagious (not transmit from person to person ).
1. Candida - C. albicans : is the most common Candida species causing CNS
infection.
2. Aspergillus : Aspergillus infections account for 5% of CNS fungal
infections.
3. Cryptococcus neoformans and Cryptococcus gattii lead to cryptococcal disease
is a common opportunistic infection in AIDS patients, particularly in
Southeast Asia and Africa.
4. parasitic meningitis ( eosinophilic meningitis ): there is a predominance
of eosinophils in the CSF.
The most common parasites implicated are Angiostrongylus cantonensis
, Gnathostoma spinigerum, Schistosoma, These parasites normally infect animals not
people, and they are not spread from one person to another. People get infected by
ingesting something that has the infectious form or stage of the parasite.
5. Non-infectious meningitis : Meningitis may occur as the result of spread of
cancer to the meninges ( neoplastic meningitis)(2)
,and certain drugs (mainly
NSAIDs , antibiotics and intravenous immunoglobulins).(3)
It may also be caused by several inflammatory conditions, such as sarcoidosis
(which is then called neurosarcoidosis).
connective tissue disorders such as systemic lupus erythematosus SLE , and
certain forms of vasculitis (inflammatory conditions of the blood vessel wall), such
as Behçet's disease. Epidermoid cysts and dermoid cysts may cause meningitis by
releasing irritant matter into the subarachnoid space.

7
Symptoms of meningitis :
Symptoms of meningitis vary with age, duration of illness and the child’s response to
infection. Findings in neonates may be minimal, and in children less than 2 years neck
stiffness (the inability to flex the neck forward passively due to increased neck muscle
tone and stiffness) may be absent but occurs in 70% of bacterial meningitis in adults.
Mainly fever, headache, photophobia, nausea and vomiting, mental confusion and
lethargy, and/or excessive irritability are the usual initial symptoms.
Even when the disease is diagnosed early and adequate therapy instituted, 5% to 10% of
patients die, typically within 24-48 hours of onset of symptoms. Bacterial meningitis
may result in brain damage, hearing loss, or learning disability in 10 to 20% of survivors.
A less common but more severe (often fatal) form of meningococcal disease is
meningococcal septicaemia which is characterized by a haemorrhagic rash. ( on the
trunk, lower extremities, mucous membranes, conjunctiva) and rapid circulatory
collapse .

8
Other signs include the presence of positive Kernig's sign that is one of the physically
demonstrable symptoms of meningitis. Severe stiffness of the hamstrings causes an
inability to straighten the leg when the hip is flexed to 90 degrees.
Brudziński sign : is a clinical sign in which forced flexion of the neck elicits a reflex
flexion of the hips. It is found in patients with meningitis ,subarachnoid hemorrhage and
possibly encephalitis .
Pseudo-meningitis (Meningism) , is a set of symptoms similar to those of meningitis but
not caused by meningitis is caused by nonmeningitic irritation of the meninges, usually
associated with acute febrile illness, especially in children and adolescents. The main
clinical signs that indicate meningism are nuchal rigidity, Kernig's sign and Brudzinski's
signs.(4)

9
Diagnosis of meningitis :
if someone is suspected of having meningitis, blood tests are performed for markers of
inflammation (e.g. C-reactive protein, complete blood count), as well as blood cultures.
Determination of C-reactive protein (CRP) concentration: Several acute-phase
reactants have been examined for their usefulness in the diagnosis of acute bacterial
meningitis. However, none is diagnostic for bacterial meningitis ,CRP, which is made in
the liver and secreted within 6 h after an acute inflammatory reaction, has been
measured in patients with meningitis , measurement of serum concentrations of CRP
had a sensitivity that ranged from 69% to 99% and a specificity that ranged from 28% to
99%.
Lumbar puncture :
The most important test in identifying or ruling out meningitis is analysis of the
cerebrospinal fluid through lumbar puncture (LP)
lumbar puncture is contraindicated if there is a mass in the brain (tumor or abscess) or
the intracranial pressure (ICP) is elevated, as it may lead to brain herniation.
This applies in 45% of all adult cases. If a CT or MRI is required before LP, or if LP
proves difficult( when skin infection , Uncorrected coagulopathy) professional
guidelines suggest that antibiotics should be administered first to prevent delay in
treatment, Often, CT or MRI scans are performed at a later stage to assess for
complications of meningitis.
*
*Cases that CT or MRI scan is recommended prior to the lumbar puncture. (5)

10
The diagnosis of bacterial meningitis rests on CSF examination
performed after lumbar puncture:
1- The CSF appearance : it may be cloudy, depending on the presence of significant
concentrations of WBCs, RBCs, bacteria, and/or protein. In untreated bacterial
meningitis. the WBC count is elevated, usually in the range of 1000–5000
cells/mm3
,with neutrophil predominance in CSF, typically between 80% and
95%; ∼10% of patients with acute bacterial meningitis present with a lymphocyte
predominance (defined as 150% lymphocytes or monocytes) in CSF. The CSF
glucose concentration is 40 mg/dL in approximately 50%–60% of patients.(6)
2-
Gram stain: The results of CSF cultures are positive in 70%–85% of patients who
have not received prior antimicrobial therapy, but cultures
may take up to 48 h for organism identification. Therefore,
several rapid diagnostic tests should be considered to determine
the bacterial etiology of meningitis.
Gram stain examination of CSF permits a rapid, accurate identification of the
causative bacterium in 60%–90% of patients with community-acquired bacterial
meningitis, and it has a specificity more or equal of 97%.
3- Latex agglutination : is simple to perform, does not require special equipment,
and is rapid (results are available in 15 min). Depending on the meningeal
pathogen, latex agglutination has shown good sensitivity in detecting the antigens
of common meningeal pathogens (7)
:
78%–100% for H. influenzae type b
67%–100% for S. pneumonia.
69%–100% for Streptococcus agalactiae.
50%–93% for N. meningitidis.

11
4- Limulus lysate assay: Lysate prepared from the amebocyte of the horseshoe crab,
Limulus polyphemus, has been suggested as a useful test for patients with
suspected gram-negative meningitis, because a positive test result suggests the
presence of endotoxin in the sample ; a correctly performed assay can detect ∼103
gram-negative bacteria/mL of CSF and as little as 0.1 ng/mL of endotoxin. One
study demonstrated a sensitivity of 93% and a specificity of 99.4%, compared with
cultures for gram-negative bacteria.
5- PCR: has been utilized to amplify DNA from patients with meningitis caused by
the common meningeal pathogens
(N. meningitidis, S. pneumoniae , H. influenzae type b) (8)
. In one study of CSF
samples obtained from 54 patients with meningococcal disease or from patients
who underwent CSF analysis and who did not have meningococcal meningitis (9)
,
the sensitivity and specificity of PCR were both 91%.
6- Determination of lactate concentration. Elevated CSF lactate concentrations
may be useful in differentiating bacterial
from nonbacterial meningitis in patients who have not received prior
antimicrobial therapy, the sensitivity of the test was 96%, the specificity was
100%. Furthermore, is not recommended due to other factors (e.g., cerebral
hypoxia/ischemia, anaerobic glycolysis, vascular compromise, and metabolism of
CSF leukocytes) also may elevate CSF lactate concentrations.

12
7- Determination of procalcitonin concentration. Elevated serum concentrations
of the polypeptide procalcitonin, which are observed in patients with severe
bacterial infection, were shown to be useful in differentiating between bacterial
and viral meningitis.(10)
*- normal CSF characteristics and main pathological alterations (11)
.

13
Management of meningitis :
Meningitis is potentially life-threatening and has a high mortality rate if untreated; delay
in treatment has been associated with a poorer outcome. Thus, treatment with wide-
spectrum antibiotics should not be delayed while confirmatory tests are being
conducted.
If meningococcal disease is suspected in primary care, guidelines recommend
that benzylpenicillin ( also known as penicillin G ,It is not a first-line agent for
pneumococcal meningitis) (12)
be administered before transfer to hospital .
Intravenous fluids should be administered if hypotension (low blood pressure)
or shock are present. Meningitis can cause a number of early severe complications,
regular medical review is recommended to identify these complications early and to
admit the person to an intensive care unit if deemed necessary.
Mechanical ventilation may be needed if the level of consciousness is very low, or if
there is evidence of respiratory failure. If there are signs of raised intracranial pressure,
measures to monitor the pressure may be taken; this would allow the optimization of
the cerebral perfusion pressure and various treatments to decrease the intracranial
pressure with medication (e.g. mannitol).
Seizures are treated with anticonvulsants (Acetazolamide) . Hydrocephalus
(obstructed flow of CSF) may require insertion of a temporary or long-term drainage
device, such as a cerebral shunt.
Acetaminophen (Tylenol)
This pain medication can provide relief neck pain and headaches to make you more
comfortable for a few hours, especially if the pain is mild to moderate in severity.

14
Treatment :
Treatment of bacterial meningitis :
Antibiotic :
. Empiric antibiotics (treatment without exact diagnosis) should be started immediately,
even before the results of the lumbar puncture and CSF analysis are known.
The choice of initial treatment depends largely on the kind of bacteria that cause
meningitis in a particular place and population.
For instance, in the UK empirical treatment consists of a third -generation cefalosporin
such as cefotaxime or ceftriaxone. In the UK, where resistance to cefalosporins is
increasingly found in streptococci, addition of to the initial treatment is recommended.
Chloramphenicol, either alone or in combination with ampicillin, however, appears to
work equally well.
Table3 : recommendation for empirical antimicrobial therapy for purulent meningitis
based on patient age and specific predisposing condition (13)
.

15
Empirical therapy may be chosen on the basis of the person's age, whether the infection
was preceded by a head injury, whether the person has undergone recent neurosurgery
and whether or not a cerebral shunt is present. In young children and those over 50 years
of age, as well as those who are immunocompromised, the addition of ampicillin is
recommended to cover Listeria monocytogenes.(14)
The results of the CSF culture generally take longer to become available (24–48 hours).
Once they do, empiric therapy may be switched to specific antibiotic therapy targeted to
the specific causative organism and its sensitivities to antibiotics .
Steroids
Additional treatment with corticosteroids (usually dexamethasone) has shown some
benefits, such as a reduction of hearing loss, and better short term neurological
outcomes in adolescents and adults from high-income countries with low rates of HIV.
Some research has found reduced rates of death(15),
They also appear to be beneficial in
those with tuberculosis meningitis .
Professional guidelines therefore recommend the commencement of dexamethasone or
a similar corticosteroid just before the first dose of antibiotics is given, and continued for
four days.
Given that most of the benefit of the treatment is confined to those with pneumococcal
meningitis.
some guidelines suggest that dexamethasone be discontinued if another cause for
meningitis is identified. (16)
The likely mechanism is suppression of overactive
inflammation.
Treatment of Viral meningitis :

16
Viral meningitis tends to run a more benign course than bacterial meningitis. Herpes
simplex virus and varicella zoster virus may respond to treatment with antiviral drugs
such as aciclovir
Viral meningitis typically only requires supportive therapy; most viruses responsible for
causing meningitis are not amenable to specific treatment., Mild cases of viral
meningitis can be treated at home with conservative measures such as fluid, bedrest, and
analgesics.
Treatment of Fungal meningitis
Fungal meningitis, such as cryptococcal meningitis, is treated with long courses of high
dose antifungals, such as amphotericin B and flucytosine.(17)

17
Prevention
For some causes of meningitis, protection can be provided in the long term through
vaccination, or in the short term with antibiotics. Some behavioral measures may also
be effective.
Behavioral
Bacterial and viral meningitis are contagious. Both can be transmitted through droplets
of respiratory secretions during close contact such as kissing, sneezing or coughing on
someone, but cannot be spread by only breathing the air where a person with meningitis
has been. Viral meningitis is typically caused by enteroviruses, and is most commonly
spread through fecal contamination. The risk of infection can be decreased by changing
the behavior that led to transmission.
Vaccination :
Since the 1980s, many countries have included immunization against Haemophilus
influenzae type B in their routine childhood vaccination schemes. This has
practically eliminated this pathogen as a cause of meningitis in young children in those
countries. In the countries in which the disease burden is highest, however, the vaccine
is still too expensive.(18)
Similarly, immunization against mumps has led to a sharp fall in
the number of cases of mumps meningitis, which prior to vaccination occurred in 15%
of all cases of mumps.

18
Meningococcus vaccines exist against groups A, B, C, W135 and Y. In countries where
the vaccine for meningococcus group C was introduced, cases caused by this pathogen
have decreased substantially. A quadrivalent vaccine now exists, which combines four
vaccines with the exception of B; immunization with this (A,C,W135,Y) vaccine is now
a visa requirement for taking part in Hajj.(19)
Development of a vaccine against group B meningococci has proved much more
difficult, as its surface proteins (which would normally be used to make a vaccine) only
elicit a weak response from the immune system, or cross-react with normal human
proteins.
Still, some countries (New Zealand, Cuba, Norway and Chile) have developed vaccines
against local strains of group B meningococci; some have shown good results and are
used in local immunization schedules.
Two new vaccines, both approved in 2014, are effective against a wider range of group
B meningococci strains.
In Africa, until recently, the approach for prevention and control of meningococcal
epidemics was based on early detection of the disease and emergency reactive mass
vaccination of the at-risk population witt bivalent A/C or trivalent A/C/W135
polysaccharide vaccines.(20)
though the introduction of MenAfriVac (is a vaccine developed for use in sub-Saharan
Africa for children and adults between 9 months and 29 years of age against
meningococcal bacterium Neisseria meningitidis group A.)

19
Routine vaccination against Streptococcus pneumoniae with the pneumococcal
conjugate vaccine (PCV), which is active against seven common serotypes of this
pathogen, significantly reduces the incidence of pneumococcal meningitis.
The pneumococcal polysaccharide vaccine (PPSV) ,the latest version known
as Pneumovax 23 (PPV-23) , which covers 23 strains, is only administered to certain
groups (e.g. those who have had a splenectomy, the surgical removal of the spleen); it
does not elicit a significant immune response in all recipients, e.g. small children, so
WHO does not recommend use of PPV in routine childhood immunization
programs.(21)
Childhood vaccination with Bacillus Calmette-Guérin (BCG) is a vaccine primarily
used against tuberculosis, has been reported to significantly reduce the rate of
tuberculous meningitis, but its waning effectiveness in adulthood has prompted a search
for a better vaccine.

20
Epidemiology of meningitis :
the exact incidence rate for meningitis is unknown Although meningitis is a notifiable
disease (A notifiable disease is any disease that is required by law to be reported to
government authorities. The collation of information allows the authorities to monitor
the disease, and provides early warning of possible outbreaks) , In 2013 meningitis
resulted in 303,000 deaths – down from 464,000 deaths in 1990.(22)
In 2010 it was
estimated that meningitis resulted in 420,000 deaths.(23)
Bacterial meningitis occurs in about 3 people per 100,000 annually in Western
countries. Population-wide studies have shown that viral meningitis is more common, at
10.9 per 100,000 and occurs more often in the summer. In Brazil, the rate of bacterial
meningitis is higher, at 45.8 per 100,000 annually. Sub-Saharan Africa has been plagued
by large epidemics of meningococcal meningitis for over a century, leading to it being
labeled the "meningitis belt". Epidemics (is the rapid spread of infectious disease to a
large number of people in a given population within a short period of time, usually two
weeks or less) typically occur in the dry season (December to June), and an epidemic
wave can last two to three years, dying out during the intervening rainy
seasons.(24)
Attack rates of 100–800 cases per 100,000 are encountered in this
area, which is poorly served by medical care. These cases are predominantly caused by
meningococci. In 1996, Africa experienced the largest recorded outbreak of epidemic
meningitis in history, with over 250,000 cases and 25,000 deaths registered. Between
that crisis and 2002, 223,000 new cases of meningococcal meningitis were reported to
WHO. The most affected countries are Burkina Faso, Chad, Ethiopia and Niger.
In 2017 during the meningitis season, the 23 countries reported a total of 29 827
suspected meningitis cases including 2276 deaths.(25)

21
How is the disease transmitted :
The bacteria are transmitted from person to person through droplets of respiratory or
throat secretions. Close and prolonged contact (e.g. kissing, sneezing and coughing on
someone, living in close quarters or dormitories (military recruits, students), sharing
eating or drinking utensils, etc.) facilitate the spread of the disease. The average
incubation period is 4 days, ranging between 2 and 10 days(26)
. Although the pattern of
epidemic cycles in Africa is not well understood, several factors have been associated
with the development of epidemics in the meningitis belt. They include: medical
conditions (immunological susceptibility of the population), demographic conditions
(travel and large population displacements), socioeconomic conditions (overcrowding
and poor living conditions), climatic conditions (drought and dust storms), and
concurrent infections (acute respiratory infections).

22
History of meningitis :
Some think that Hippocrates may have realized the presence of meningitis, as known to
pre-Renaissance physicians such as Avicenna.(27)
It appears that epidemic meningitis is
a relatively recent phenomenon.
The first recorded case occurred in 1805 in Geneva.(28)
Several other epidemics in
Europe and the United States were described shortly afterward, and the first report of an
epidemic in Africa appeared in 1840. African epidemics became much more common in
the 20th century, starting with a major epidemic sweeping Nigeria and Ghana in 1905–
1908.
The first report of bacterial infection underlying meningitis was by the Austria
bacteriologist Anton Weichselbaum, who in 1887 described
the meningococcus.(29)
Mortality from meningitis was very high (over 90%) in early
reports. In 1906, antiserum was produced in horses; this was developed further by the
American scientist Simon Flexner and markedly decreased mortality from
meningococcal disease.
In 1944, penicillin was first reported to be effective in meningitis.The introduction in
the late 20th century of Haemophilus vaccines led to a marked fall in cases of
meningitis associated with this pathogen,and in 2002, evidence emerged that treatment
with steroids could improve the prognosis of bacterial meningitis. World Meningitis
Day is celebrated on 24 April each year.

23
Summary
1- Meningitis maybe life-threating case , caused by bacterial , viral , fungal and
parasitic infections and non-infectious meningitis .the most dangerous is bacterial
meningitis , the most common is viral meningitis .
2- Symptoms Mainly fever, headache, photophobia, nausea and vomiting, mental
confusion and lethargy, and/or excessive irritability are the usual initial
symptoms.
3- The diagnosis of the meningitis by the CRP , CSF analysis , gram stain , Latex
agglutination, Limulus lysate assay and procalcitonin concentration .
4- in meningococcal disease , guidelines recommend that benzylpenicillin , Seizures
are treated with anticonvulsants (Acetazolamide), to decrease the intracranial
pressure with medication (e.g. mannitol), Acetaminophen (Tylenol) to relief
neck pain and headaches.
5- The vaccination against meningitis is Bacillus Calmette-Guérin (BCG) , (PPSV)
vaccine and quadrivalent vaccine , which reduce the ratio of meningitis around
the world .
6- meningitis is a notifiable disease ,
7- Some think that Hippocrates may have realized the presence of meningitis ,The
first report of bacterial infection underlying meningitis was by the Austria
bacteriologist Anton Weichselbaum, in 1887.

24
References
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et al. Emerging Infections Programs Network. Bacterial meningitis in the
United States, 1998-2007.
2- Gleissner B, Chamberlain MC (May 2006). "Neoplastic meningitis". The
Lancet. Neurology.
3- The Challenge of Drug-Induced Aseptic Meningitis German Moris, MD; Juan
Carlos Garcia-Monco, MD .
4- https://www.sciencedirect.com/topics/medicine-and-dentistry/meningism
5- Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM,
Whitley RJ (November 2004). "Practice guidelines for the management of
bacterial meningitis"
bacterial meningitis" Same source p 1269
7- Gray LD, Fedorko DP. Laboratory diagnosis of bacterial meningitis. Clin
Microbiol Rev 1992.
8- Tunkel AR. Bacterial meningitis. Philadelphia: Lippincott Williams &
Wilkins, 2001.
9- Ni H, Knight AI, Cartwright K, et al. Polymerase chain reaction for diagnosis
of meningococcal meningitis.
10- Nathan BR, Scheld WM. The potential roles of C-reactive protein and
procalcitonin concentrations in the serum and cerebrospinal fluid in the
diagnosis of bacterial meningitis. In: Remington JS, Swartz MN, eds. Current
clinical topics in infectious diseases, vol 22. Oxford: Blackwell Science,.

25
11- Klein J.O., Feigin R.D., McCracken Jr. G.H. Report of the task force on
diagnosis and management of meningitis. Pediatrics 1986
12- WHO Model Formulary 2008 . World Health Organization. 2009. pp. 98, 105
13- Chaudhuri A, Martinez-Martin P, Martin PM, Kennedy PG, Andrew Seaton
R, Portegies P, Bojar M, Steiner I (July 2008). "EFNS guideline on the
management of community-acquired bacterial meningitis: report of an EFNS
Task Force on acute bacterial meningitis in older children and adults".
European Journal of Neurology.
.
bacterial meningitis"
15- Assiri AM, Alasmari FA, Zimmerman VA, Baddour LM, Erwin PJ, Tleyjeh
IM (May 2009). "Corticosteroid administration and outcome of adolescents
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Proceedings.
16- Chaudhuri A, Martinez-Martin P, Martin PM, Kennedy PG, Andrew Seaton
R, Portegies P, Bojar M, Steiner I (July 2008). "EFNS guideline on the
management of community-acquired bacterial meningitis: report of an EFNS
Task Force on acute bacterial meningitis in older children and adults".
European Journal of Neurology.
17- Bicanic T, Harrison TS (2004). "Cryptococcal meningitis" (PDF). British
Medical Bulletin.
18- Segal S, Pollard AJ (2004). "Vaccines against bacterial meningitis" . British
Medical Bulletin.
19- Wilder-Smith A (October 2007). "Meningococcal vaccine in travelers". Current
Opinion in Infectious Diseases.

26
20- WHO (September 2000). "Detecting meningococcal meningitis epidemics in
highly-endemic African countries" . Releve Epidemiologique Hebdomadaire.
21- WHO " Pneumococcal vaccines". Archived from the original on March 6,
2002. Retrieved 2009-05-29.
22- GBD 2013 Mortality Causes of Death Collaborators (January 2015). "Global,
regional, and national age-sex specific all-cause and cause-specific mortality for
240 causes of death, 1990–2013
23- Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al.
(December 2012). "Global and regional mortality from 235 causes of death for
20 age groups in 1990 and 2010"
24- Greenwood B (1999). "Manson Lecture. Meningococcal meningitis in Africa".
Transactions of the Royal Society of Tropical Medicine and Hygiene .
25- -WHO ,2018, "Weekly epidemiological record" ,No 14, p 177
26- WHO ,2018, "Weekly epidemiological record" ,No 14, p 294
27- Arthur Earl Walker; Edward R. Laws; George B. Udvarhelyi (1998).
"Infections and inflammatory involvement of the CNS". The Genesis of
Neuroscience. Thieme. pp. 219–21 .
28- http://www.austincc.edu/microbio/2704w/nm.htm
29- Weichselbaum A (1887). "Ueber die Aetiologie der akuten Meningitis cerebro-
spinalis". Fortschrift der Medizin (in German).

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