Epidemic Encephalitis B: Gu Junsheng

EPIDEMIC ENCEPHALITIS B The First Teaching Hospital of Zhengzhou University, Department of Infectious Disease

Gu Junsheng

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DEFINITIONS • •

1.Encephalitis Encephalitis, commonly shortened from encephalomyelitis, refers to an inflammatory process always involving both the brain and spinal cord, sometimes only the brain. 2

DEFINITIONS • •

1.Encephalitis This process is either due directly to infection or a secondary immunological response to infection, the former being termed invasive encephalitis and the latter allergic encephalitis. 3

DEFINITIONS •

2.Invasive encephalitis Invasive encephalitis includes all those infections in which direct viral invasion of the CNS occur. The infections can be caused by many kinds of virus such as arbovirus, herps simplex virus, enterovirus and EB virus etc. 4

DEFINITIONS •

3.Allergic encephalitis Allergic encephalitis refers those which are“postinfectious”after a common acute non-CNS infection followed by an immune-reactive demyelinating process (demyelinization). 5

DEFINITIONS 4.Epidemic encephalitis • Since 1917 ， a number of epidemics have broken out all over the world, such as Eastern/Western equine encephalitis in Americas, Murray Valley encephalitis in Australia, Russian Spring-Summer encephalitis in Russia, & Japanese B encephalitis in the Far East that are all caused by arboviruses. •

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DEFINITIONS 5.Epidemic encephalitis B • Epidemic encephalitis B is a severe arboviral disease that mainly occurs in summer & fall in eastern Asia (Siberia, Korea, Japan etc.). • High fever, convulsions, disturbance of consciousness, Babinski’s sign, meningeal signs & respiratory failure are all typical manifestations of epidemic encephalitis B. •

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DEFINITIONS • •

5.Epidemic encephalitis B Since the first case of epidemic encephalitis B is reported in Japan, it is also called Japanese B Encephalitis. Continuous endemic virus transmission has also been proved or is suspected in Southeast Asia, the Philippines, and East Indies etc. 8

EPIDEMIC ENCEPHALITIS B •

—Today, epidemic encephalitis B is our only topic.

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ETIOLOGY Virus causing epidemic encephalitis B belongs to the Togaviridae family, Flavivirus. • One kind of arbovirus. •

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ETIOLOGY •

The term arbovirus is an abbreviation of arthropod-borne virus, a group consisting predominantly of the togavirus & bunyavirus which cause many kinds of disease. The diseases are all transmitted by an arthropod vector(such as mosquitoes & ticks ) and the reservoir may be man or an animal species. 11

ETIOLOGY Epidemic Encephalitis B Flavivirus Togaviridae

HCV

HGV

Dengue Fever …… Epidemic Hemorrhagic Fever

Arbovirus

Bunyaviridae …… Other families

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ETIOLOGY •

Epidemic arbovirus encephalitis is often preceded by an epizootic in the animal reservoir.

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ETIOLOGY •

The antigenicity of epidemic encephalitis B virus is stable, so host can get permanent immunity after either clinical or subclinical infection.

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EPIDEMIOLOGY • Source of infection: • Epidemic encephalitis B is a zoonosis. Humans and animals ( such as swine, horses, ox, dogs, chickens, ducks, gooses, & wild birds ect. ) can become sources of infection in the phase of viremia.

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EPIDEMIOLOGY • Source of infection: • Animals play a more important role in the transmission of epidemic encephalitis B since: • the viremia period is longer • the infection rate of animal is higher • the virus amount in their blood is higher 16

EPIDEMIOLOGY • Route of Transmission: • Epidemic encephalitis B is transmitted by mosquitoes (mainly from Culex, Anopheles, Aedes ). Virus in mosquitoes will not produce mosquito encephalitis, they just live through the winter and pass the virus to their babies transovarially. 17

EPIDEMIOLOGY • Route of Transmission : • If humans and animals are bitten by infected mosquitoes, they may be infected also. So mosquito is not only the reservoir of epidemic encephalitis B but also the transmission vector.

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EPIDEMIOLOGY • Susceptible group: • This disease spare neither age nor sex. • Inapparent infection (covert infection /subclinical infection) is very common. The ratio of inapparent infection to apparent infection in Chinese is 1000-2000:1.

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EPIDEMIOLOGY • Susceptible group: • In hyperendemic areas, over 70 per cent of adult populations surveyed have antibodies. • Patients of epidemic encephalitis B are mainly children because of the high inapparent infection rate and the permanent post-infection immunity. 20

EPIDEMIOLOGY • Epidemic features: • 1. Epidemic encephalitis B is world wide but mainly occurs in east and southeast Asia.

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EPIDEMIOLOGY • Epidemic features: • 2. Cases occur sporadically throughout the entire year in tropical zone, but in the subtropical and temperate zone, the greatest number always occurs during summer and autumn.

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EPIDEMIOLOGY • Epidemic features: • 3. Epidemic encephalitis B is highly sporadic, epidemic outbreak in a short period is rare (helpful to diagnosis)

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PATHOGENESIS • • •

Virus reaches the CNS following: Introduction at a distant portal of entry Intracellular replication (during the period of non-specific immunity in phagocytes) & • Subsequent viremia

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PATHOGENESIS •

The interval between initial infection and eventual CNS involvement may be days or weeks. Elimination of the virus through nonspecific immunity by phagocytes is weak & slow and more effective elimination will be started mainly by activised cytotoxic T cells and Killer cells through ADCC ( antibody dependent cell-mediated cytotoxicity) in specific immunity.

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PATHOGENESIS •

•

Factors that influence the disease are varied. If the person can eliminate the virus before it enter the CNS, the infection will be inapparent, or else, encephalitis comes. ? 26

PATHOLOGY •

Gross examination of the brain and cord reveals: • edema • congestion • small hemorrhages

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PATHOLOGY • •

Microscopic examination shows: Perivascular cellular infiltration and infiltration of the meninges, chiefly with infiltration lymphocytes • The principal lesion in the parenchyma consists of neuronic necrosis and degeneration accompanied by neuronophagocytosis. • Perivascular cuffing and glial proliferation are common. 28

PATHOLOGY •

In CNS, lesions are mainly in gray matter and, the upper it goes, the more severe the lesions are.(mainly in cerebral cortex, diencephalon, mesencephalon) 29

CLINICAL MANIFESTATIONS • •

Incubation period: often 10~14 days

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CLINICAL MANIFESTATIONS •

There are 3 stages in typical epidemic encephalitis B, but no clear demarcations between each one.

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CLINICAL MANIFESTATIONS • •

1. Prodromal period : The onset of epidemic encephalitis B is marked by fever, steep rising to 39 ~ 40 degrees Celsius, headache, dizziness, drowsiness, nausea, `vomiting, etc. In some cases, stiffness of the neck may be seen in this period. The prodromal period often lasts 1 ~ 3 days. 32

CLINICAL MANIFESTATIONS • •

2. Period of apparent manifestations

In this stage, typical clinical manifestations can be seen as followings:

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CLINICAL MANIFESTATIONS •

2. Period of apparent manifestations

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(1) High fever • Temperature of patients often exceed 40 degrees Celsius, lasting 7 to 10 days or longer. 34

CLINICAL MANIFESTATIONS •

2. Period of apparent manifestations

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(2) Disturbance of consciousness • The disturbance of consciousness of patients may vary from mild alteration of consciousness to deep coma.

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CLINICAL MANIFESTATIONS •

2. Period of apparent manifestations

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(2) Disturbance of consciousness

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Somnolence: when asked, the patient will be easily woken up and give right answers & then fall into sleep again when left alone. (answer correctly) • Confusion: characterized by disorientation, & always give the wrong answer. ( answer incorrectly ) 36

CLINICAL MANIFESTATIONS •

2. Period of apparent manifestations

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(2) Disturbance of consciousness Stupor: the patient is difficult to be woken up and often give an irrelevant answer. (answer irrelevantly ) • Coma: give no response to sound. ( answer nothing ) 37

CLINICAL MANIFESTATIONS •

2. Period of apparent manifestations

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(2) Disturbance of consciousness

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Delirium: Another state of

disturbance of consciousness, characterized by hyperexcitability with confusion, disorientation, illusion, or delusion etc. 38

CLINICAL MANIFESTATIONS •

2. Period of apparent manifestations

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(3) Convulsions:

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`Mechanisms

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CLINICAL MANIFESTATIONS •

2. Period of apparent manifestations

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(3) Convulsions:

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High fever, inflammation and edema and other lesions of the parenchyma can change the excitability of the neurons in CNS and then may result in convulsions, always accompanied with muscular rigidity and disturbance of consciousness. 40

CLINICAL MANIFESTATIONS •

2. Period of apparent manifestations

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(4) Respiratory failure:

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Definitions: Causes: Category:I/II centric/peripheral 41

CLINICAL MANIFESTATIONS •

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2. Period of apparent manifestations

(4) Respiratory failure: Centric respiratory failure is often seen in severe cases because of the damage of respiratory center in the brain stem.

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CLINICAL MANIFESTATIONS •

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2. Period of apparent manifestations

(4) Respiratory failure: The main differences between and peripheral respiratory failure alteration of respiratory rhythm, always become irregular in the (epidemic encephalitis B).

centric is the which former

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CLINICAL MANIFESTATIONS •

2. Period of apparent manifestations

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(5) Other clinical manifestations of nervous system

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Clinical manifestation of nervous system always occur within 10 days and new symptoms & signs will be rare after 2 weeks. 44

CLINICAL MANIFESTATIONS •

2. Period of apparent manifestations

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(5) Other clinical manifestations of nervous system

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Attenuation (or disappearance ) of superficial reflexes, hyperreflexia of deep tendon reflexes, appearance of pathologic reflexes which reflex the lesion of the `pyramid (pyramidal tract) (such as Babinski sign, Oppenheim sign, Gordon sign, Chaddock sign), triad signs of meningeal irritation (stiff-neck rigidity, Kernig sign & Brudzinski sign), are all common clinical manifestations in epidemic encephalitis B. 45

CLINICAL MANIFESTATIONS •

2. Period of apparent manifestations

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(5) Other clinical manifestations of nervous system

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Abnormal neurological signs, including cranial nerve palsies, cerebellar ataxia, extrapyramidal tremors (etc.) are variably present and usually bear little anatomical relationship ( indicating the widespread, diffusive nature of the pathology ). 46

CLINICAL MANIFESTATIONS •

2. Period of apparent manifestations

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(5) Other clinical manifestations of nervous system

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In patients with coma, there may be tonic paralysis with increased muscular tonicity, or even with muscular tetanus, sometimes with paralysis of the `urinary bladder and/or rectal colon. Flaccid paralysis of the extremities may be seen in cases with poliomyelitis that occasionally encountered. 47

CLINICAL MANIFESTATIONS • •

2. Period of apparent manifestations High fever, convulsions, and respiratory failure are the most severe symptoms of epidemic encephalitis B in this period. They are `correlate and always exacerbate each other. Respiratory failure in comatose cases always drive the patients into death between the seventh and tenth days. 48

CLINICAL MANIFESTATIONS • •

2. Period of apparent manifestations Headache, vomiting are two common symptoms in patients with increased intracranial pressure & papilledema may be detected as one of the important signs, always along with palsies of cranial nerves III and VI. • Period of apparent clinical manifestation generally lasts about a week. 49

CLINICAL MANIFESTATIONS • •

3. Convalescent period After the period of apparent clinical manifestation, fever subsides gradually, and neurological signs always resolve by the end of the second week. 50

CLINICAL MANIFESTATIONS • •

3. Convalescent period In severe cases, patients always undergo a prolonged recovery, often leaving permanent sequelae. 51

CLINICAL MANIFESTATIONS • 3. Convalescent period • The occurrence of sequelae correlate with the severity of the acute stage of illness. Young children are most susceptible. 52

CLINICAL MANIFESTATIONS • •

3. Convalescent period Sequelae, including mental impairment, emotional lability, tremor, parkinsonism, motor paralysis, and pathopsychologic syndromes etc. have been reported in up to 75 per cent of patients. `Epilepsy may exist in whole life. 53

CLINICAL MANIFESTATIONS •

3. Convalescent period Convalescent period always lasts half of a month or longer, depending on the severity of the disease. 54

CLINICAL MANIFESTATIONS •

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Clinical types

Epidemic encephalitis B is divided into 4 clinical types according to the clinical manifestations: mild type, common type, severe type & `fulminating type. 55

LABOLATORY TESTS •

1. The peripheral white blood cell count shows a moderate leukocytosis (10~20x109/L) early in the disease (usually characterized by neutrophilia) but lymphocytosis later.

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LABOLATORY TESTS • • •

2. Cerebrospinal fluid: Appearance: clear Pressure: always increased (normal?) WBC count: (50-500)x106/L, sometimes > 1000x106/L.

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LABOLATORY TESTS • •

2. Cerebrospinal fluid: The pleocytosis: polymorphonuclear early but predominantly mononuclear later. • Protein: mildly elevated. • Glucose: normal

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LABOLATORY TESTS •

3. Serology:

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Specific antibody (IgM): can be detected for early diagnosis appear after 2 days of onset in C.S.F after 3~4 days of onset in blood

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LABOLATORY TESTS • •

4. Virus isolation: Virus may be isolated from the brain of dead patients during the first week of onset. • Virus is cultivatable from C.S.F of about 1/3 patients who progress to a fatal outcome. • Rarely from the nonfatal cases • Rarely from the blood of patients 60

DIAGNOSIS •

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Diagnosis information mainly get from:

1. Epidemiology: summer or fall children within 10 years old 2. History: typical symptoms & signs such as urgent onset of high fever, headache, vomiting, disturbance of consciousness, convulsions, pathological reflex, signs of meningeal irritation etc 61

DIAGNOSIS •

Diagnosis information mainly get from:

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3. Laboratory tests: increased WBC & neutrophilia aseptic alteration of C.S.F. 4. Specific IgM: help to make the definite diagnosis 62

DIFFERENTIAL DIAGNOSIS •

Other disease of the CNS that may be confused with epidemic encephalitis B

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DIFFERENTIAL DIAGNOSIS CNS infections caused by other microorganisms such as bacilli, other viruses, tuberculosis meningitis, non-infection diseases such as tumor, trauma, and `abscess of the brain should be differentiated. • Alcohol, drugs, and other toxins must also be considered in a review of possible causes. •

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PROGNOSIS •

A poor prognosis is associated with prolonged high fever, frequent or prolonged seizures, high protein content in the cerebrospinal fluid, Babinski signs, and early appearance of respiratory depression. • Mortality is less than 10%, but can also be as high as 20~50% in severe type & fulminating type. 65

TREATMENT •

Although there is no specific antivirus therapeutic agent can be gotten & the treatment of epidemic encephalitis B is altogether symptomatic, it is very beneficial when given early in the course of the disease before necrotic brain damage occurs or intracranial pressure apparently increased. 66

TREATMENT •

Emphasis should be put on dealing with severe symptoms such as high fever, convulsions, and respiratory failure etc.

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TREATMENT •

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General therapy Supportive nursing care is essential & may reduce mortality. The correction of fluid, electrolyte & acid-base disturbances (caused by fever, vomiting & insufficient oral intake ) are important, especially in very young patients. 68

TREATMENT • •

General therapy

Fluid of 1500~2000 ml/d to adults & 50~80 ml/kg.d. to children should be given intravenously. More fluid should be avoided for the possibilities of exacerbating the cerebral edema. 69

TREATMENT •

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Symptomatic therapy

High fever: Control of high fever by sponging or ice packs and administration of antipyretics orally or rectally are recommended.

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TREATMENT •

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Symptomatic therapy

High fever: Chlorpromazine & phenergan (each 0.5~1mg/kg i.m.q4~6h.) can be used in patients with severe convulsions.

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TREATMENT • •

Symptomatic therapy Convulsions: Prompt administration of

anticonvulsants ( intravenous diazepam, 0.1~0.3mg/kg in children or 10~20mg in adults, or chloral hydrate, 100x (age of year) mg each time for children, 1~2g each time for adults through `enema for acute control ) should be used to prevent protracted seizures and attendant hypoxia. 72

TREATMENT •

Symptomatic therapy

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Convulsions: Barbital

is often used for prevention of convulsions (5~8 mg /kg in children & 0.1~0.2g in adults).

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TREATMENT •

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Symptomatic therapy

Respiratory failure: Management of airways in semicomatose and comatose patients is essential. Arterial blood gases should be monitored and respiratory assistance provided if hypoxia occurs.

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TREATMENT •

Symptomatic therapy

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Respiratory failure: Prevention and

treatment of secondary bacterial infections may be required & good pulmonary toilet and care of urinary `catheters are essential. 75

TREATMENT •

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Symptomatic therapy

Respiratory failure: If clinical signs (deepening obtundation; prolonged delirium) suggest cerebral edema or if the cerebrospinal fluid pressure is very high (>400 mm H2O ), measures to reduce brain swelling are indicated. 76

TREATMENT •

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Symptomatic therapy

Respiratory failure: Intracranial pressure monitoring Osmotic agents ( 20% mannitol 1~2 /kg q 4~6 h iv or ivgtt within 20 ~30 minutes )

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PREVENTION • • • •

Protection of susceptible groups: Vaccination 6-12 months for the first time 1 year later for the second time

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EPIDEMIC ENCEPHALITIS B The First Teaching Hospital of Zhengzhou University, Department of Infectious Disease Gu Junsheng

THANKS! 79