1.

Fever

: Pathogenesis and Treatment

2. Meningitis and Encephalitis

Diagnosis

Reference: Textbook of pediatrics, Nelson, 17th edition Recommendation for the management of fever in children. 200504,

Fever, Definition
A controlled increase in body temperature over the normal values for an individual.

Normal body temperature

Thermosensitive neurons: preoptic or anterior hypothalamus Diurnal variation

Thermoregulatory response
1.
2.

Redirecting blood to or from cutaneous vascular beds

Increased or decreased sweating

3.

Extracellular fluid volume regulation (via arginine vasopressin)

Behavior responses

4.

Pathogenesis of Fever
1. Bodys thremostat has been reset at a higher temperature. Thermoregulatory response in fever is the same as that in normal temperature maintance. Thermostat is response to endogenous pyrogens.

2.

3.

Endogenous pyrogens
1. Cytokines : IL-1, IL-6, TNF-, IFN - and lipids : produced by stimulated leukocytes or other cells PGE2

2.

Exogenous pyrogens

1.

Includes Microbes, Microbial toxins, or other products of Microbess

2.

These substance could stimulate macrophages and other cells to produce endogenous pyrogens

Other substances associated with fever

Antigen-antibody complexes (in the presence of complement), complement components, lymphocyte products, bile acids, androgenic steroid metabolites.

was produced within the body and capable of stimulating endogenous pyrogens

Endotoxin

Can either directly affect hypothalamus and stimulate endogenous pyrogen release

Fever maybe caused by following conditions:

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. Infection Vaccines Biological agents Tissue injuries Malignancy Drugs Rheumatic disorder Inflammatory disease Granulomatous disease Endocrine disorders Metabolic disorders Genetic disorders Factitious fever

(GM-CSF, IFN, IL-) (Infarction, emboli,--) (as in amphotericin B) (SLE, RA)

(thyrotoxicosis,----)

Consequence associated with fever

1. 2. Increase oxygen consumption Increase carbon dioxide production

3.
4.

Increase cardiac output

Increase risks of benign febrile seizure for children between the ages of 6 month to 5 years.

10

Fever pattern (1)

1.Very high temperature 2.Intermittent fever 3.Sustained fever 4.Remittent fever 5.Relapsing fever 6.Biphasic fever 7.Periodic fever
Meaning: BT > 41oC Possible associated condition: central fever, malignant hyperthermia, malignant neuroleptic syndrome, drug fever, heatstroke

11

Fever pattern (2)

1.Very high temperature 2.Intermittent fever 3.Sustained fever 4.Remittent fever 5.Relapsing fever 6.Biphasic fever 7.Periodic fever
Meaning: exaggerated circadian rhythm that includes a period of normal temperature on most days (extremely wide variation: Septic, hectic)

Possible associated condition: Most viral infection

12

Fever pattern (3)

1.Very high temperature 2.Intermittent fever 3.Sustained fever 4.Remittent fever 5.Relapsing fever 6.Biphasic fever 7.Periodic fever
Meaning: Persistent and did not vary by more than 0.5 oC/24hr

13

Fever pattern (4)

1.Very high temperature 2.Intermittent fever 3.Sustained fever 4.Remittent fever 5.Relapsing fever 6.Biphasic fever 7.Periodic fever
Meaning: Persistent and varies by more than 0.5 oC/24hr

14

Fever pattern (5)

1.Very high temperature 2.Intermittent fever 3.Sustained fever 4.Remittent fever 5.Relapsing fever 6.Biphasic fever 7.Periodic fever
Meaning: Characterized by febrile periods that are separated by intervals of normal temperature, such as tertian fever and quartan fever

Possible associated condition: Plasmodium vivax (tertian fever), Plasmodium malariae (quartan fever)

15

Fever pattern (6)

1.Very high temperature 2.Intermittent fever 3.Sustained fever 4.Remittent fever 5.Relapsing fever 6.Biphasic fever 7.Periodic fever
Meaning: A single illness with 2 distinct periods of fever over 1 or more weeks Possible associated condition: Poliomyelitis is the classic example; Some hemorrhagic fever including dengue fever and African hemorrhagic fever (Ebola, Lassa, Marburg)

16

Fever pattern (7)

1.Very high temperature 2.Intermittent fever 3.Sustained fever 4.Remittent fever 5.Relapsing fever 6.Biphasic fever 7.Periodic fever
Meaning: To describe fever syndromes with a regular periodicity Possible associated condition: Cyclic neutropenia, PFAPA, Familiar Mediterranean fever, Hibernian fever, Hyper IgD syndrome

17

Relative tachycardia:
Noninfectious etiology Infectious disease in which toxin is responsible for the clinical manifestation. (Temperature-pulse dissociation)

Relative bradycardia:

Typhoid fever Brucellosis Leptospirosis Drug fever Conduction defect from cardiac involvement in: acute rheumatic fever, Lyme disease, viral myocarditis, infective endocarditis

18

Treatment of fever (1)

1.

Other than providing symptoms relief, use of antipyretics does not change the course of infectious disease.

2.

Fever with temperature less than 39 oC in healthy children generally do not require treatment.

19

Treatment of fever (2)

1. Administration of antipyretics is recommended in the following condition: 1. chronic cardiopulmonary diseases, 2. metabolic disorders, 3. neurologic diseases, or 4. in those who are at risk of febrile seizure.

20

Treatment of fever (3)

Recommend medication: cycloxygenase inhibitor 1.
1.

Acetaminophen, 10-15 mg/kg orally q4h

Renal (Prolonged use), hepatic (overdose)

2.
1.

Ibuprofen, 5-10 mg/kg orally q 6-8 hr

Dyspepsia, GI bleeding, etc.

Tepid sponge bathing ( not alcohol)

21

Meningitis and Meningoncephalitis

Two of acute infection of central infections

22

Meningitis and meningoencephalitis (1)

Pathogen:

Virus Bacteria
In neonatal period:

(most common)

E coli, GBS, Listeria

Beyond neonatal period:

Pneumococcus, Neisseria meningitidis, Hib

Fungal and parasites

Rickettsiae
As Rocky Moutain sptted fever
23

(least common)

Meningitis and meningoencephalitis (2)

Common symptoms
Headache, nausea, vomiting, anorexia, restlessness, irritability
most are nonspecific

Common Signs:
Photophobia, neck pain and rigidity, seizures, obtundation, stupor, coma, focal neurologic deficits Depends on the specific pathogen, the host, and the area of CNS affected

24

Meningitis and meningoencepalitis (3)

Diagnosis: CSF study:
Includes : Cytology (WBC/DC, RBC), Gram stain Biochemistry (protein, glucose, and others such as Immunoglobulin,
lactate, etc),

Culture for bacteria, virus, or fungus,

Antibodies detection for specific pathogen PCR or RTPCR

Image study
25

Meningitis and meningoencepalitis (4)

Contraindication for lumbar puncture:
1. 2. Elevated ICP owing to a suspected mass lesion Symptoms and signs of pending cerebral herniation in a child with probable meningitis Critical illness Skin infection at the site of the LP Thrombocytopenia (platelet < 20000/mm3)

3. 4. 5.

26

Meningitis and meningoencephalitis (5)

Normal CSF:

WBC: up to 5 WBC/mm3, and no PMN

(NB: up to 15 /mm3, and 1 2 PMN /mm3 may be present)

RBC: should be absent

If present, it indicates either traumatic tapping (supernatant is clear) or subarachnoid hemorrhage (supernatant is xanthomatic)

Biochemistry:
Protein : 10 40 mg/dL for child more than 3 months old
(NB: as high as 120 mg/dL) Immunoglobulin: test CSF for oligoclonal band if MS is suspected

Glucose: 60 % of the blood glucose

27

Meningitis (4)
Elevated PMN account: bacterial meningitis or early phase of an aseptic meningitis

Elevated Lymphocyte count: aseptic, tuberculosis, or fungal meningitis, or other non-infectious process
Elevated CSF protein was seen in many conditions, including infectious, immunologic, tumor, vascular, or degenerative process Diffuse hypoglycorrhachia is found in association with diffuse meningeal disease, particular bacterial and tuberculous meningitis

28

Encephalitis
Pathogen:
1. 2. 3.

4. 5.

Enterovirus Arbovirus ( through mosquitoes, and ticks, such as JBE) Herpes virus (HSV-1, 70 % mortality if no antiviral therapy; HSV-II in neonates or sexually active adolescent; VZV) EBV Mumps ( occasionally deafness was notes as a sequale)

Common symptoms/sign:
1. 2. 3. 4.

Those seen in meningitis Mental dullness, stupor, bizarre movements and convulsions. Focal neurologic sign Loss of bowel and bladder control
29

Encephalitis

Diagnosis:

Brain biopsy : virus isolation, EM, or PCR CSF study: for cytology, virus isolation, PCR or RTPCR, Image: MRI

Serological study

30

Thanks for your attentation

31