NEUROTROPIC VIRUSES

Dr. EDHIE DJOHAN UTAMA, SpMK

Meningitis : Characterized by high

fever, headache, stiff neck

Encephalitis : Characterized by

changes in mental state, consciousness (kesadaran), behavior (tabiat)

Brain Abscess : Headache, focal

signs and seizures indicate a brain abscess. There are also characteristic computed tomography (CT) and magnetic resonance image (MRI) findings

INFEKSI PADA SISITIM SYARAF PUSAT

BISA DISEBABKAN OLEH SEMUA AGENT YANG INFECTIOUS :
= BAKTERI PYOGENIK = MYCOBACTERIA = FUNGI = SPIROCHAETA = VIRUS

INFEKSI SELAPUT OTAK

I. MENINGITIS PURULENTA
MENINGOCOCCUS (40%) PNEUMOCOCCUS HAEMOPHILUS INFLUENZAE STAPHYLOCOCCUS AUREUS LISTERIA MONOCYTOGENES

II. MENIGITIS GRANULOMATOUS

MYCOBACTERIUM TUBERCULOSIS COCCIDIODES IMMITIS (meningitis) CRYPTOCOCCUS NEOFORMAN (meningitis) HISTOPLASMA CAPSULATUM TREPONEMA PALLIDUM JAMUR JAMUR LAIN

III. ASEPTIC MENINGITIS

ENTEROVIRUS POLIOMYELITIS COXSACKIEVIRUS ECHOVIRUS (Enteric Cytopathic Human Orphan) RABIES HERPES SIMPLEX PARAMYXOVIRUS (Mumps virus) LEPTOSPIRA CLOSTRIDIUM TETANI

ASEPTIC MENINGITIS

ENTEROVIRUS
POLIOMYELITIS COXSACKIEVIRUS ECHOVIRUS (Enteric Cytopathic Human Orphan)

RABIES HERPES SIMPLEX PARAMYXOVIRUS (Mumps virus) LEPTOSPIRA CLOSTRIDIUM TETANI

VIRAL MENINGITIS

ENTEROVIRUS
POLIOMYELITIS COXSACKIEVIRUS ECHOVIRUS (Enteric Cytopathic Human Orphan)

RABIES HERPES SIMPLEX PARAMYXOVIRUS (Mumps virus)

ENTEROVIRUS
Enterovirus termasuk PICORNAVIRIDAE POLIOMYELITIS COXSACKIEVIRUS Group A dan B ECHOVIRUS (Enteric Cytopathic Human Orphan) TRANSMISI :

RESPIRATORY DROPLETS FECAL ORAL (fingers, foodstuffs, milk flies and cockroaches)

Port de antre : alimentary tracts

PATHOGENESIS

Enhancement factors :
During pregnancy Corticosteroids

Multiplications :
Lymphoid tissue of gut and pharynx Reticuloendothelial system

Target organs :
Spinal cord brain meningenes myocardium skin.

Pathology :
Cells injury intrauterine transfer of Cocksacchieviruses Severe and fatal disease Severe neural damages paralytic poliomyelitis

GROWTH IN TISSUE CULTURE

Depend on the virus : Can growth in Mokey kidney tissue or Human cells (Diploid cell culture or human fetal kidney tissue) or gray minkey tissue culture. Cytophatic Effect on the tissue culture.

COLLECTING SPECIMENS & DIAGNOSE

Specimens :
Feces 4 8 gr / (rectal swab) Pharyngeal swab CSF Blood ( 10 20 cc) / serum for antibody tests Vesicle fluids Conjunctival swabs Urine ( 10 cc)

Times of collection
After onset of illness third/fourth weeks of illness

Volume of the specimens :

Accute phase / during illness / convalescent phase

Laboratory Diagnosis

Direct examination of specimens Isolation of viral agents / Isolation on tissue cultures Serological diagnosis
Neutralization test Complemen fixation Haemagglutination Inhibition antibodies Pssive hemagglutination test

Infections of Neural Tissue Viral Polio = poliomyelitis

fecal/oral route of transmission spread by contaminated water 90% asymptomatic infections 10% flu-like illness 0.01% paralytic poliomyelitis Replicates inside epithelial cells of nose, throat, intestine lymphatics bloodstream If enters CNS infected cells die paralytic polio Historical rate of paralytic polio US - 21,000/yr
Peak year US - 1958 Last case wild virus in US - 1979 Western hemisphere declared free - 1994 Discontinuation of oral polio vaccine - 1999 Worldwide eradication

Poliomyelitis
1.

The symptoms of poliomyelitis are usually headache, sore throat, fever, stiffness of the back and neck, and occasionally paralysis (less than 1% of cases). Poliovirus is found only in humans and is transmitted by the ingestion of water contaminated with feces. Poliovirus first invades lymph nodes of the neck and small intestine. Viremia (free viruses in the blood) and spinal cord involvement may follow. Replicate in the motor neurons at the anterior horn of spinal cord. Death of the cells results in paralysis of the muscle innervated by these neurons. The viruses also affects the brain stem result with respiratory paralysis (bulbar poliomyelitis)

2.

3.

4. Diagnosis is based on isolation of the virus from feces and

throat secretions or by rise in antibody titer.

Poliovaccine
5. The Salk vaccine (an inactivated polio vaccine, IPV) involves injection of formalin-inactivated viruses and boosters every few years.

6. The Sabin vaccine (oral polio vaccine, OPV) contains three attenuated live strains of poliovirus and is administered orally.
Polio will be eliminated through vaccination.

VACCINE POLIOMYELITIS

SALK VACCINE : parenteral

Menghasilkan humoral AB Diberikan 4kali dalam 1-2 tahun Efektivitas 70-90%

SABIN VACCINE : per oral

Trivalent vaccine Idealnya diberikan pada usia 6 bulan berturut turut 3 kali jarak 6-8 minggu Efektivitas 100% Menghasilkan IgM, IgG dan secretory IgA dalam saluran pencernaan Dengan prasyarat pemberian vaksin

Anak sehat Tidak baru baik sakit Tidak prematur / malnutrisi / daya tahan sedang jelek

COXSACKIE VIRUSES

Group A : Herpangina (fever, sore throat and tender vescicle in the oropharynx. Hand Food and Mouth disease : vesicular rash on the hands and feet and ulcerations in the mouth (children) Group B : Pleurodynia (Bornholm disease, epidemic myalgia,devils grip) characteristic by fever and severe pleuritic chest pain. Myocardial and pericarditis (chest pain and congestive failure) Both groups can cause aseptic meningitis, mild paresis and transient paralysis. Diagnosis : virus isolated or rise in titer of neutralizing antibody.

ECHOVIRUS

ECHO = acronym of Enteric cytophatic Human orphan

Cause of variety of disease such as asceptic meningitis, upper respiratory infection, febrile illness with or without rash, imfantile diarrhae and haemorrhagic conjuctivitis.
Fecal oral Pathogenesis : similar to enteroviruses.

Diagnosis : virus isolated from tissue culture.

Viral meningitis = aseptic meningitis

Fairly common (40%) Self-limiting, non-fatal CSF is clear Many different viruses
1. Enteroviruses - 40%

Poliovirus Cocksachievirus Echovirus

2. Mumps virus - 15% 3. Other

Infections of Neural Tissue Viral - RABIES

Rabies - Rhabodovirus Bite, Multiplies at site and enter the damage nerve tissue (demyelinated nerve tissue). Travels to local nerves Peripheral nerves spinal cord brain Long incubation (tergantung lokasi gigitan) Phases :
Prodromal phase - flulike symptoms, tingling, burning, depression Excitation phase - muscle function, speech, vision, anxiety, hydrophobia Paralytic phase - muscles weaken, consciousness fades, death.

Mortality - 100% with best treatment Post exposure prophylaxis (PEP) - has never failed in US

Rabies, is usually acquired through the bite of a rabid warm-blooded animal.

This virus spreads by axonal transport from the inoculated skin or muscle to the corresponding dorsal root ganglion or anterior horn cells and then to populations of neurons throughout the CNS. The early involvement of neurons of the limbic system cause the typical behavioral changes of clinical rabies.

Rabies
1.

Rabies virus (rhabdovirus) causes an acute, usually fatal, encephalitis called rabies.

2.

Rabies may be contracted through the bite of a rabid animal, by inhalation of aerosols, or invasion through minute skin abrasions. The virus multiplies in skeletal muscle and connective tissue.
Encephalitis occurs when the virus moves along peripheral nerves to the CNS.

3.
4.

Symptoms of rabies include spasms of mouth and throat muscles, followed by extensive brain and spinal cord damage and death.
Hydrophobia

5.

Rabies
5. Laboratory diagnosis may be made by direct immunofluorescent tests of saliva, serum, and CSF or brain smears (animal).

6. Reservoirs for rabies in the United States include skunks, bats, foxes, and raccoons. Domestic cattle, dogs, and cats may get rabies. Rodents and rabbits seldom get rabies. 7. Current postexposure treatment includes administration of human rabies immune globulin (RIGH) along with multiple intramuscular injections of vaccine. 8. Preexposure treatment consists of vaccination.

VIRUS PENYEBAB ENCEPHALITIS

TOGAVIRIDAE (Genus Alphavirus) Chikungunya Eastern equine encephalitis (EEE), transmisi nyamuk Culiseta Western Equine Encephalitis (WEE), transmisi oleh nyamuk Culex St.Louis Encephalitis (SLE), trasmisi oleh nyamuk Culex California Encephalitis (CE), transmisi oleh nyamuk Aedes triseriatus FLAVIVIRUS Flavivirus berukuran kecil (40 nm), berbeda dalam morfogenesis dan berbeda dalam struktur genomnya dari Togavirus Yang teriinfeksi sering menyebabkan encephalitis, dasarnya adalah neurotrofik khususnya pd binatang pengerat VIRUS RABIES Progressive encephalitis terjadi jika virus mencapai / menyebar ke CNS, gejala klinis hyrdophobia

Arboviral Encephalitis
1.

Symptoms of encephalitis are chills, headache, fever, and eventually coma.

2. Many types of arboviruses transmitted by mosquitoes cause encephalitis. 3. The incidence of arboviral encephalitis
increases in the summer months when mosquitoes are most numerous.

Arboviral Encephalitis
5. Diagnosis is based on serological tests.

6. Control of the vector is the most effective way to control encephalitis.

4. Horses are frequently infected by EEE (eastern equine encephalitis) and WEE (western equine encephalitis) viruses.

MUMPS VIRUS

Member of Paramyxovirus : only in human Transmision :saliva containing virus / air droplets Clinical aspect : infected of salivary glands enter the blood stream Complication : Collection of specimens :
Blood Spinal fluid orchitis & meningitis / meningoencephalitis

Viral isolation / embryonated eggs Serological diagnosis :

Microscopic examination :

CF / HAI / Nt antibodies

acidophilicintracytoplasmic inclusions Immunofluorescent antibody technic

Lymphocytic Choriomeningitis Virus

Lymphocytic Choriomeningitis Virus is a member of the Arenavirus family. Rare cause of Aseptic meningitis

Cannot be disitinguished clinically from frequent viral causes. (Echovirus, Cosackievorus or

mumps viorus)

Diagnosis : isolate the virus or increase titer antibody.