There are nearly 100 viruses of the herpes group that infect many different animal species. Official name of herpesviruses that commonly infect human is Humans herpesvirus (HHV) herpes simplex virus types 1 (HHV 1) Herpes simplex virus type 2 (HHV 2) Varicella-zoster virus (HHV 3) Epstein-Barr virus, (HHV 4) Cytomegalovirus (HHV 5) Human herpesvirus 6 (HHV 6) Human herpesvirus 7 (HHV 7) Human herpesvirus 8 (HHV 8) (Kaposi's sarcoma-associated herpesvirus). Herpes B virus of monkeys can also infect humans hELMINTHS#corona virus#Aspergillosis#BUGANDO#CUHAS#CUHAS#CUHAS#CNS INFECTIONS

1. CNS INFECTIONS
1
DR.HAMISI MKINDI,MD.
TO DOWNLOAD CONTACT: hermyc@live.com

2. Presentation Layout
• Introduction
• Epidemiology
• Etiology
• Pathogenesis
• Diagnosis
• Treatment
• Prevention
2

3. Introduction
• CNS infections refers to the infections involving any part of the CNS
due to various organisms.
• The parts involved can be Meninges (Meningitis), Brain
Parenchyma(Encephalitis, Abscess) or Spinal cord (Myelitis).
• Organisms involved are Bacteria, Viruses, Fungi and Protozoa.
• A number of non infectious etiologies may account for syndromes
that resemble CNS infections e.g. CNS Tumors, autoimmune
• They are accompanied with significant morbidity and mortality.(in
Botswana 2004-2015, Meningitis Survey, mortality due Meningitis
was between 46-65% at 10 weeks – 1 year. Gottberg et al1).
3

4. Bacteria Meningitis
Part 1
4

5. Meningitis
• Refers to inflammation of the meninges (leptomeningitis vs
pachymeningitis)
• It can be classified based on
 Aetilogy – Bacterial, Viral, Fungal or Parasitic
 Duration – Acute, Subacute.?? or Chronic
 Setting of acquisition – Community, Hospital Acquired
• Acute meningitis is clinically defined as a syndrome characterized by
the onset of meningeal symptoms/signs over the course of hours to
up to several days
5

6. Epidemiology of Meningitis
• 1 million cases B.Meningitis reported in
Africa (1991-2010). Deaths – 100,000 *
• 30,000 cases annually along the belt
• African Meningitis belt with highest
incidence of meningitis due to
N.meningitides. NmA has decreased due
to MACV. Other serotypes cont. to cause
outbreak particulary NmC
• Thus Non-NmA,S.Pneumoniae and Hib
continue to be the common isolates for
B.meningitis in African Meningitis belt2 (A
study in five W.African countries**).
**Burkina Faso,Chadi,Mali,Niger,Togo
*WHO data
6

7. In Tanzania
• 136 patients with meningitis were enrolled (fever (85%), meningism(63%) &
impairment of consciousness(33%))
• 39% of patients (esp < 5 years) confirmed to have bacterial meningitis
• Haemophilus influenzae (26% esp < 2 years), Streptococcus pneumoniae (19%)
and Neisseria meningitidis (15%)
• However there is difference in the trend of aetiologies as compared to study by
Matee et al in 20013, whereby, the commonest isolates were S.pneumoniae
(36.4%),H.influenzae (16.4%) C.neoformans (12%) among 1144 CSF samples of
which 222 were had positive bacterial or fungal growth
• In Matee’s study, 55% of the isolates, were from children aged less than fifteen
years.
7

8. Aetiologies of Meningitis
8

9. Age- related Bacteria Pathogens causing Meningitis
Age Bacterial Pathogens
< 1month Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes
1- 23 months Streptococcus agalactiae, Escherichia coli, Haemophillus influenzae,
Streptococcus pneumoniae, Neisseria meningitidis
2 – 50 years Streptococcus pneumoniae, Neisseria meningitidis
> 50 years Streptococcus pneumoniae, Neisseria meningitidis, Listeria,
monocytogenes, aerobic gram negative bacteria
9

10. Predisposing Factors in Meningitis
Condition Commonest organisms
Basilar skull fracture Streptococcus pneumoniae, Haemophillus influenzae,
group A β- hemolytic streptococcus
Head trauma; post
neurosurgery; CSF
shunts
Staphylococcus aureus, Staphylococcus epidermidis,
aerobic gram negative bacteria (including Pseudomonas
aureginosa)
Immunocompromise
d state
Streptococcus pneumoniae, Neisseria meningitidis,
Listeria, monocytogenes, aerobic gram negative bacteria
(including Pseudomonas aureginosa)
10

11. Acute Bacterial Meningitis - Pathogenesis
• Source and route of infection
• Pattern of spread of agent to CNS
• Virulence of the agent
• Site involved
• Host’s immunity, presence or absence
of undelying risk factors/comorbidities
11

12. Pathogenesis Cont..
Pathogenic Event Bacteria Factors Host factors
Mucosal colonization Fimbriae, polysaccharide capsule,
IgA protease production,
bacteriocins
Mucosal epithelium, secretory IgA,
cilliary activity, anticapsular
antibodies
Intravascular survival Polysaccharide capsule Complement activation, organism-
specific antibodies
Meningeal invasion Fimbriae, association with
monocytes, ibe 10, OmpA, PAF
receptor, pneumococcal choline
binding protein A
Blood –brain barrier
Blood – CSF barrier
Survival in the subarachnoid space Polysaccharide capsule Poor opsonic activity
12

13. Pathogenesis cont..
13

14. Clinical Presentations
14

15. 15

16. Diagnosis
• History and physical examination and
confirmed by CSF analysis ±
neuroimaging studies
• Specimen: CEREBRAL SPINAL FLUID
by lumbar puncture
• Collection
• - How ?
• - Contraindication ?
• Transport
• Processing
• •Precautions to be taken prior to
spinal tap
• CSF –
Microscopy,Culture,Susceptibility
16

17. Parameters to be assessed in CSF
Appearance: clear, colorless (normal CSF), purulent, cloudy (bacterial) and clear/slightly turbid (
viral or tuberculosis or cryptococcal)
17

18. Other tests
• FBP –WBCs,PLTs,Hb
• Blood culture (+ 50%)
• Acute phase reactants – CRP,Procalcitonin
• GeneXpert MTB/Rif**
• Other samples from suspected primary
focus of infection eg: blood, sputum,
wound swab, etc for culture and
sensitivity
• ± RFT (Meningococcaemia)
• Imaging – CT Scan
• PCR (role in Nm surveillance)
• ??urine dipstick
18

19. Management
• Early and prompt management of patients with meningitis reduce mortality and adverse
neurological outcomes
• Initial empirical antimicrobial therapy*after CSF and blood samples taken; then modified
as per susceptibility results
• In case of brain abscess: + surgical drainage
• Role of corticosteroids( for S.pneumoniae and H.influenzae CAM)
• Supportive management for semiconsious/uncounsious:nasogastrict tube for feeding;
intubation/O2; urinary catheterization etc
*focus on local common organisms and drug susceptibility patterns
19

20. 20

21. Prevention
• Bacterial meningitis vaccines have largely
decreased the incidences of meningitis especially
in children:
• A polyvalent vaccine from the capsular
polysaccharide of groups A, C, Y and W-135 strains
for Neisseria meningitidis.
• Conjugate vaccine for type B Haemophillus
influenzae
• PCV - for Streptococcus pneumoniae
• •Quarantine/isolation in meningococcal
meningitis
• •Other preventive and control measures ??? –
Hib, N.meningitides – contact chemoprophylaxis
with rimfapicin (also ciprofloxacin, ceftriaxone).
Given to identified contacts within 24hrs of pt’s
diagnosis and if contacts occurred more than 14
days no need.
• The incidence rate of PCV-7: 18.0 to
4.6/100,000 population
• PCV-10 non-PCV-7: 5.7 to 1.3/100,000
population
• PCV-13 non-PCV-10: 5.7 to 0.8/100,000
population
• What is situation in Tanzania ≥ 7 years after
introduction PCV,Hib..??
21

22. Encephalitis
• Definition – is inflammation of the brain parenchyma especially by
infection with a virus and less by bacterial, protozoa,fungal or
autoimmune.
• It is commonly accompanied by inflammation of meninges leading to
Meningoencephalitis
• It can be either Primary or Secondary encephalitis
22

23. Clinical types
• Primary Encephalitis – Occurs when a virus or other agent directly
infects the brain. The infection may be concentrated in one area or
widespread and usually is due to reactivation of a virus that had been
inactive e.g HSV or VZV from cranial nerve ganglia
• Secondary Encephalitis – is due to faulty immune system reaction
following to infection elsewhere in the body. Instead of attacking the
organisms, the immune system also attack the healthy brain cells and
occurs two –three weeks post infection
23

24. Aetiologies
24

25. Clinical presentations
• Signs and symptoms develops hours to week after exposure.
• Calssic symtpoms: fever, headache and brain aberration
(disorientation, neurologic deficits, seizures)
• Increased ICP - Alteration in consciousness, nausea, vomiting.
• Brainstem involvement may present with nystagmus, decreased
extraocular movement, hearing loss, dysphagia, dysarthria,
respiratory abnormalities and motor movement.
• Limbic encephalitis – cause mood and personality changes that may
progress to memory loss and delirium
25

26. Diagnostic criteria for Encephalitis
Major criteria(required)
Patients presenting to medical attention with altered mental status(decreased level of consciousness,
lethargy or personality change) lasting ≥24hrs with no alternative cause
Minor criteria ( 2 required for possible encephalitis;≥3 required for probable or confirmed encephalitis)
Documented fever ≥380C within the 72 hrs before presentation
Generalised or partial seizures not fully attributable to a pre existing seizure disorder
New onset of focal neurological findings
CSF leukocyte count ≥ 5/mm3
Abnormality of brain parenchyma on neuroimaging suggestive of encephalitis that is either new from prior
studies or appears acute in onset
Abnormality on EEG that is consistent with encephalitis and not attributable to another cause
26

27. Diagnosis
• Laboratory investigations4
• CSF Analysis
• Serology – Role of Immunoglobulins
• PCR*
• VDRL
• BS
• Neuroimaging – CT Scan , MRI(preferred to CT Scan)
• EEG
27

28. Management – 3Es
• Emergent Issues: signs of increased ICP/cerebral oedema
• Mannitol, hypertonic saline
• Refractory cases consider –neurosurgical intervention i.e. hemicraniectomy,
lobectomy
• Epileptic issues: seizures control with AEDs
• Etiology : identify the etiology and treat accordingly
• HSV – treat with I.V Acyclovir 10mg/kg 8hrs x 14-21 days
• Autoimmune – corticosteroids, IV immunoglobulin+plasmapharesis
28

29. Brain Abscess
Part 2
29

30. Definition
• A focal intracranial infection that is initiated as an area of cerebritis
and evolve into collection of pus surrounded by vascularized capsule
• Common organisms causing Brain Abscess are Bacteria and fungi
• In more than one third of cases, it is due polymicrobial infection
30

31. Epidemiology
• In the US about 1500-2500 cases occurs annually
• In developing countries, it is estimated the prevalence is about 8% of
ICSOL(in HICs – 1-2% of all ICSOL)
• M:F – 3:1
• Median age of onset is 30-40 yrs
• 20 to otitic focus occurs to those <20 or >40 yrs
• 20 to PNS Infection – 30-40yrs
• 25% in children is secondary to Otitis Foci and CHD
• 0.2% are due to cranial operations(iatrogenic)
• The incidence of fungal brain abscess has increased due to use of broad
spectrum antibiotics and steroids/immunosuppressive agents
31

32. Etiologies and predisposing factors
32
Predisposing condition Common isolates
Otitis media or mastoiditis Streptococci (anaerobic or aerobic), Bacteroides and Prevotella spp., Enterobacteriaceae
Sinusitis (frontoethmoid or
sphenoid)
Streptococci, Bacteroides spp., Enterobacteriaceae, Staphylococcus aureus, Haemophilus spp.
Dental sepsis Mixed Fusobacterium, Prevotella and Bacteroides spp., streptococci
Penetrating trauma or
postneurosurgical
S. aureus, streptococci, Enterobacteriaceae, Clostridium spp.
Lung abscess, empyema,
bronchiectasis
Fusobacterium, Actinomyces, Bacteroides and Prevotella spp., streptococci, Nocardia spp.
Bacterial endocarditis S. aureus, streptococci
Congenital heart disease Streptococci, Haemophilus spp.
Neutropenia Aerobic gram-negative bacilli, Aspergillus spp., Mucorales, Candida spp.
Transplantation Aspergillus spp., Candida spp., Mucorales, Enterobacteriaceae, Nocardia spp., Toxoplasma gondii
Human immunodeficiency virus
infection
T. gondii, Nocardia spp., Mycobacterium spp., Listeria monocytogenes, Cryptococcus neoformans

33. Pathogenesis
• Sources
• Contiguous source – 30-50%
• Haematogenous dissemination/trauma – 20-35%
• Cryptogenic – 10-35%
33

34. Contiguous spread
• Route of contiguous spread
• Direct extension through osteoitis/osteomyelitis
• Retrograde thrombophlebitis via diploic/emissary vein
• Localisation
• Otitis media – temporal lobe/cerebellum abscess
• Paranasal sinusitis – frontal lobe abscess
• Sphenoid Sinusitis – Temporal lobe abscess
• Dental infection – Frontal lobe abscess
34

35. Hematogenous spread
• Bacteremia commonly cause Multiple brain abscesses mostly in the
distribution of MCA and gray white matter junction.
• Distant sources – lung diseases,wound and skin
infection,osteomyelitis, pelvic intraabdominal infection
• CHD(TOF*/TGV) – account by 60% of brain abscess case( children)
*TOF – chronic hypoxemia –polycythaemia-increased viscosity-multiple infarcts at Grey-White junction-mileu
for bacteria growth
• Less 5% of patients with IF despite presence of continuous
bacteremia
35

36. Trauma
• Open cranial fracture with dural breach/foreign body injury/ as
sequala of neurosurgery
• Include those 20 to compound depressed skull fracture,dog bite.
• in military population usually is due to retained bone fragments or
contamination of initially uninfected missile site with bacteria from
skin,clothes or the environment
36

37. Stages of abscess formation
1. Early Cerebritis
Days 1-3: perivascular
inflammation characterized
by neutrophils infiltration
occurs around the site of focal
infection with surrounding
area of edema
37

38. Cont …
2.Late cerebritis
Day 4-9:A central area of necrosis
develop as the surrounding
edema progress. Peripheral
accumulation of fibroblasts
preludes the development of a
capsule
38

39. Cont …
3.Early Capsule
Day 10-14: establishment of a
ring-enhanced capsule of well
vascularized tissue with further
fibroblasts migration and adjacent
reactive astrocytosis
39

40. Cont..
4.Late Capsule
Day 14 and beyond: Collagen
fibres and granulation tissue
deposition leads to a thickening of
the capsule effectively walling off
the area of suppurative infection
40

41. Clinical presentation
• In two third of cases symptoms are present within two weeks with 8
days mean diagnosis after onset of symptoms
• Course may range from indolent to fulminant
• Presentations is not specific leading to delayment in establishing dx
• Most of the symptoms are direct results of the size and location of
Brain Abscess (SOL).
• The triad of fever, headache and focal neurological deficits is
observed in less then 50% of the patients
• 1/3rd is polymicrobial
41

42. Clinical presentations
Symptoms/Signs Frequency
Headache 69-70%
Altered mental status 65%
Focal neurological deficits 50-65%
Fever 45-53%
Seizures 25-35%
Nausea and Vomiting 40%
Nuchal rigidity 15%
Papilloedema 9-51%
42

43. 43

44. Investigations
• Imaging investigations
• CT Scan of the Brain – diagnosis, localization, treatment follow up
• MRI
• Lab Investigations
• FBP
• ESR,CRP
• Blood culture
• CSF Analysis
• Pus – microscopy, culture
44

45. Treatment
• Definitive treatment
• Surgical intervention
• Medical intervention (antimicrobial alone)
• Supportive treatment
• Anticonvulsants
• Steroids
• Other supportive treatments
45

46. Surgical intervention - indication
• Significant mass effect exerted by a lesion(on CT/MRI)
• Proximity to the ventricles – likelihood of intraventricular rupture
• Evidence of significant increase of ICP
• Poor neurological condition
• Traumatic abscess associated with foreign material
• Fungal abscess
• Multiloculated abscess
46

47. Medical treatment
• Patients with medical conditions that increase the risk associated with
surgery
• Multiple abscess
• Abscess in the deep or dominant location
• Coexisting meningitis or ependymitis
• Early reduction of the abscess with clinical improvement after
antimicrobial therapy
• Abscess size less than 3 cm.
47

48. Duration of therapy
• Post –surgical excision- course of 3-4 weeks of antimicrobial therapy
• Medical therapy alone – 12 weeks with parenteral drugs ( or 6-8
weeks of I.V antibiotics then 2-3 months of oral antibiotics)
• A combination of surgical aspiration or removal of all abscess of larger
than 2.5cm in diameter, followed by six weeks or more of
antimicrobial therapy and weekly neuroimaging of abscess resolution
• Repeat neuroimaging studies – biweekly for up to three months after
completion of therapy
48

49. Empirical medical treatment
49

50. 50

51. 51

52. Supportive Treatment
• Steroids
• May results into improvement of neurological symptoms and signs
• Useful in patients with
• Associated oedema and mass defects
• Progressive neurological deterioration
• Impending cerebral herniation
• Dose : dexamethasone 10mg 6hrly initially then tapered once the patient has
stabilized. Prolonged use is discrouraged
• Anticonvulsants
• Initiated early and continued at least up to 1 years due to high risk of post
Brain Abscess sequalae
52

53. Prognosis
• The advent of antimicrobial and imaging studies (CT Scan&MRI), the
mortality rate has reduced by 10%.
• Rupture of brain abscess is fatal.
• Long term neurological sequalae after the infection are dependent of
early dx and proper management.
53

54. References:
1. Gottberg A,Meintjes G. Meningitis;a frequently fatal Diagnosis in Africa.The Lancet
2019,19(6):676-678
2. Soeters HM,Diallo OA et al.Bacterial Meningitis Epidemiology in five countries in the Meningitis
belt of Sub-Saharan Africa,2015-2017. The J Infect Dis,2019;220(suppl 4):165-174
3. Matee M,Matre R.Pathogenic isolates in Meningitis patients in Dar es Salaam,Tanzania.East
Africa Medical Journal 2001,78(9):458-460
4. Vankateson A,Romergryko G.Diagnosis and Management of Acute
Encephalitis.Neurology;Clinical Practice,2014;206-215
5. Hoffman O,Weber JR.Pathophysiology and treatment of bacteria Menignitis.Ther Adv Neurol
Disord,2009,2(6);401-412
6. Mandell, Bennett, & Dolin: Principles and Practice of Infectious Diseases, 8th ed., Copyright © 2014
Churchill Livingstone, An Imprint of Elsevier.
7. Bokhari MR,Mesfin FB.Brain Abscess.[Updated 2019 Dec 12].In:StatPearls.
8. Google search
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