INFECTIOUS DISEASES EMERGENCY

dr. Andi Sulistyo Haribowo, SpPD

Diphtheria

Gram +ve Bacilli and Colonies

Epidemiology

Case-fatality rate

Selected Recent Diphtheria Outbreaks in Great Britain

The Scandinavian Outbreak

The Seattle Outbreak

• 1971-82 • 72 cases, nine deaths (four from obstruction) • Important roles of skin infections, Native Americans, “Skid Row” residents • “Diphtheria Dick” ,alone cost $11,000 • Total cost in $millions

Back in the (former) USSR
• Outbreak began in 1990 in Russia • All NIS affected by 1994 • >50,000 cases and 1,500 deaths in 1995 • Adults predominant • Exported to Europe and UK

Cases of diphtheria - New Independent States of the former Soviet Union, 1965-1995. (Source MMWR, 45:32, August 16, 1996.)

Diphtheria Epidemiology
 Reservoir  Transmission  Temporal pattern Human carriers Usually asymptomatic Respiratory Skin and fomites rarely Winter and spring

 Communicability

Up to several weeks without antibiotics

Diphtheria Clinical Features
 Incubation period 2-5 days (range, 1-10 days)  May involve any mucous membrane  Classified based on site of infection anterior nasal pharyngeal and tonsillar laryngeal cutaneous ocular genital

Pharyngeal and Tonsillar Diphtheria
• Insidious onset of exudative pharyngitis • Exudate spreads within 2-3 days and may form adherent pseudo membrane • Membrane may cause respiratory obstruction • Fever usually not high but patient appears toxic

Thick Membrane

Pseudo membrane

‘Bull Neck’

Skin Lesions

Diphtheria Complications
• Mostly attributable to toxin • Severity generally related to extent of local disease • Most common complications are myocarditis and toxic neuritis with palsy • Death occurs in 5%-10% for respiratory disease

Laboratory findings
• Routine examination
– Leukocytosis, 10~20 G/L, neutrophil is dominant. – Low platelet count (thrombocytopenia), rise profiles of the serum enzyme tests and proteinuria were found in serious cases.

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Laboratory findings
• Bacteriological examinations
– Smear and gram stain can found C. diphtheriae, but can not identify from the diphtheroids.

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Laboratory findings
• Bacteriological examinations
– Fluorescent antibody-stain can found toxigenic C. diphtheriae, favourable for early diagnosis, but definitive diagnosis (false positive).

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Laboratory findings
• Bacteriological examinations
– C. diphtheriae can be cultured from the swabs from nose, pharynx or other sites.

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Laboratory findings
• Immunological examinations
– Schick’ test (not to be used any more), positive result supports diagnosis – Specific antibody detection. Positive results deny the diagnosis since it is a protective antibody.

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Complications
• Most complications of diphtheria, including death, are attributable to effects of the toxin. • The severity of the disease and complications are generally related to the extent of local disease. • The most frequent complications of diphtheria are myocarditis and neuritis.

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Complications
• Myocarditis
– Present as abnormal cardiac rhythms and can occur early in the course of the illness or weeks later, and can lead to heart failure and abrupt deterioration (sudden death). – If myocarditis occurs early, it is often fatal.

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Complications
• Neuritis
– Most neuritis often affect motor nerves and usually recovers completely. – Paralysis of the soft palate is most frequent during the third week of illness.

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Complications
• Neuritis
– Eye muscles, limbs, and diaphragm paralysis can occur after the fifth week. – Secondary pneumonia and respiratory failure may result from diaphragmatic paralysis.

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Complications
• Other complications
– Include otitis media and respiratory insufficiency due to airway obstruction, especially in infants.

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Diagnosis
• Clinical diagnosis is usually made based on the epidemiological data and clinical presentation since it is imperative to begin presumptive therapy quickly.

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Diagnosis
• Gram stain of material from the pseudomembrane can be helpful when trying to confirm the clinical diagnosis.

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Diagnosis
• Culture of the lesion is even important to confirm the clinical diagnosis. It is critical to take a swab of the pharyngeal area, especially any discolored areas, ulcerations, and tonsillar crypts.

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Diagnosis
• If diphtheria bacilli are isolated, they must be tested for toxin production by ELISA or Elek test. • If toxin test is positive, the definitive diagnosis can be made. • The presence of staphylococci and streptococci do not rule out diphtheria.

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Diagnosis
• In patients with negative culture and prior antibiotic therapy, the presumptive diagnosis may be confirmed with evidences: • (1) isolation of the C. diphtheriae from culturing of close contacts, and/or (2) a low or nonprotective diphtheria antibody titer in sera (<0.1 I.U.) or Schick test (-).

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Differential diagnosis
• Dyspnea – Acute laryngitis; foreign body in trachea; laryngeal edema • Pseudomembrane – Streptococcal pharyngitis – Oral candidiasis – Infectious mononucleosis – Vincent’s angina
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Differential diagnosis
• Streptococcal pharyngitis – The pus covering on the tonsils sometimes is misunderstood as the pseudomembrane of diphtheria. It’s usually yellow in color, and easy to remove.

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Differential diagnosis
• Oral candidiasis – The oral candidiasis often occurs in infants. The general conditions of such patients are very well. The membrane is very white, and easy to remove

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Differential diagnosis
• Infectious mononucleosis and Vincent’s angina – Sometimes also have things like membranes on the surface of tonsils or pharynx. However, they can be remove without bleeding of the tissues.

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Prognosis
• The overall case-fatality rate for diphtheria is about 5%, with higher death rates (up to 20%) in persons <5 and >40 years of age.

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Treatments
• Strict isolation • Use antitoxin and antibiotics for neutralization of free toxin, elimination of further toxin production and to control local infection. • Use supportive interventions during disintoxication.

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Treatments
• General measures – Relax on bed for more than 3 weeks, 4-6 weeks for patients with myocarditis. – Provide adequate energy and nutriments

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Treatments
• Diphtheria antitoxin

– Diphtheria antitoxin, produced in horses. – It will not neutralize toxin that is already fixed to tissues, but will neutralize circulating toxin. – Early use will prevent progression of disease. – The earlier, the better.

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Treatments
• Diphtheria antitoxin – Dose: 3-5×104 U for early (<3-4d) and mild or ordinary patients; 6-10 ×104 U for later (>3-4d) or grave patients; reduce in larynx diphtheria – 1-2×104 U is given intravenously and the rest is given intramuscularly.

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Treatments
• Diphtheria antitoxin – The patient must be tested for sensitivity before antitoxin is given. – Respiratory support and airway maintenance should also be administered as needed. (Pseudomembrane shedding often happens during disintoxication)

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Treatments
• Antibiotics – Prevention of further toxin production. – Control local infection. – Reduction of transmission.

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Treatments
• Antibiotics – Procaine penicillin G daily, intramuscularly (300,000 U/day for those weighing 10 kg or less and 600,000 U/day for those weighing more than 10 kg) for 7-10 days. – Erythromycin orally or by injection (40-50 mg/kg/day; maximum, 2 gm/day) for 14 days.

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Treatments
• Antibiotics – The disease is usually not contagious 48 hours after antibiotics are used.

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Preventions
• Management of infection sources – Isolation of patients (>7d), or elimination of the organism should be documented by two consecutive negative cultures after therapy is completed.

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Preventions
• Management of infection sources – Persons with suspected diphtheria should be given antibiotics and antitoxin in adequate dosage and placed in isolation (7d) after the provisional clinical diagnosis is made and appropriate cultures are obtained.

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Preventions
• Management of infection sources – For close contacts, especially household contacts, a diphtheria booster, appropriate for age, should be given. Antitoxin 1000-2000 U, intramuscularly

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Preventions
• Management of infection sources – Contacts should also receive antibiotics— benzathine penicillin G or a 7- to 10-day course of oral erythromycin.

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Preventions
• Interruption of the transmission routes by disinfections of discharges and articles of patients

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Preventions
• Protect the susceptibles by vaccination – The effective measure – Primary series (DTP, multivalent vaccine) given at age of 3, 5, 6 months. – Boosters (DTP) given at 15 months and 4-6 years old, and booster (DT) every 10 years after then.

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Summary of the definition
• Acute, communicable, toxin-mediated, sometime life-threatening bacterial disease • Preventable with widespread immunization

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Summary of the definition
• Pseudomembrane usually in the throat or nose

• The typical pseudomembrane is adherent to the tissue, and forcible attempts to remove it cause bleeding.

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Diphtheria Antitoxin (DAT)
• • • • Produced in horses First used in the U.S. in 1891 Used only for treatment of diphtheria Neutralizes only unbound toxin

Tetanus

Tetanus – Epidemiology
• Uncommon in the US but not worldwide • 1 million cases worldwide per year • Mortality rate of 20-50%

• Highest prevalence in developing countries

Epidemiology
• Fewer than 50 cases per year in the US • Majority of cases in temperate climates (Texas, California, and Florida)

• Mortality rate of 11%
• Most who develop it have an inadequate immunization history • Only 27% of Americans older than age 70 have adequate immunity to tetanus

Pathophysiology
• Wound contamination with Clostridium

tetani

• Motile, nonencapsulated, anaerobic, gram positive rod

• Spore forming and ubiquitous in soil and animal feces

Pathophysiology
• Usually introduced in the spore forming state, then germinates to the toxin producing vegetative form • Requires decreased tissue oxygen tension to germinate • Vegetative state produces two exotoxins – Tetanolysin – Tetanospasmin

Toxins
• Tetanolysin – clinically insignificant • Tetanospasmin
– Neurotoxin responsible for the clinical manifestations of tetanus – Reaches peripheral nerves by hematogenous spread and retrograde intraneuronal transport – Does not cross blood brain barrier – Reaches CNS by retrograde transport

Tetanospasmin
• Acts on the motor end plates of skeletal muscle, in the spinal cord, and in the sympathetic nervous system Prevents release of inhibitory neurotransmitters glycine and gammaaminobutyric acid (GABA)

Clinical Features
• Tetanospasmin responsible for generalized muscular rigidity, violent muscular contractions, and instability of the ANS. • Typical wound is a puncture, but no wound is identified in up to 10% • Other routes are surgical procedures, otitis media, abortion, umbilical stump and drug abusers

Four Clinical Forms
• Local • Generalized • Cephalic • Neonatal

Local Tetanus
• Rigidity of the muscles in proximity to the site of injury • Usually resolves completely in weeks to months

• May develop into generalized

Generalized Tetanus
• Most common form • Most common presenting complaint is pain and stiffness of the masseter muscles (Lockjaw) • Short axon nerves affected initially therefore starts in the face, then neck, trunk, and extremities

Generalized Tetanus
• Muscle stiffness leads to rigidity • Trismus and characteristic sardonic smile develops (risus sardonicus) • Reflex convulsive spasms and tonic muscle contraction create dysphasia, opisthotonos (arching of back and neck), flexing arms, clenching fists, and lower extremity extension

Trismus and Sardonic Smile

Opisthotonos

Generalized Tetanus
• Autonomic nervous system
– Hypersympathetic state – Usually in the second week
• • • • Tachycardia HTN Diaphoresis Increased urinary catecholamines

– Significant morbidity and mortality

Cephalic Tetanus
• Results from an injury to the head or otitis media • Cranial nerves affected most commonly the seventh

• Poor prognosis

Neonatal Tetanus
• 400,000 worldwide deaths annually • Results from inadequately immunized mothers • Frequent after unsterile treatment of the cord stump

Neonatal Tetanus
• Signs
– Weakness
– Irritability – Inability to suck

• Presents in the 2nd week of life

Diagnosis
 Clinical diagnosis  No laboratory confirmatory tests

 Wound cultures not very useful as C. tetani may be recovered without tetanus
 Immunization history usually unknown or inadequate

Tetanus Ddx
• Strychnine poisoning • Dystonic reaction • Hypocalcemic tetany • Peritonsillar abscess • Peritonitis • Meningeal irritation • Rabies • TMJ

Treatment
• Admit to ICU • Be prepared for intubation with neuromuscular blockade as respiratory compromise may develop • Minimal environmental stimuli to avoid reflex convulsive spasms • Initial wound debridement to improve oxygenation

Treatment
• Tetanus Immunoglobulin (TIG)
– Neutralizes wound and circulating tetanospasmin – Does not neutralize toxin already bound to the nervous system – Does not improve clinical symptoms – Decreases mortality

Treatment
• TIG
– Usual dose is 3,000 to 6,000 units – Administered IM opposite side as Td given – Give before wound debridement

Treatment
• Antibiotics
– Questionable utility but usually given – Metronidazole
• antibiotic of choice

– Avoid penicillin
• it is a GABAA antagonist and may worse symptoms

Treatment
• Muscle relaxants
– Tetanospasmin
• prevents neurotransmitter release at inhibitory interneurons and therapy of tetanus is aimed at restoring balance

– Midazolam
• preferred agent as it is water soluble

– Baclofen
• specific GABAB agonist that has also been used

Treatment
• Neuromuscular blockade
– Blockade often required to allow respiration and to prevent fractures and rhabdomyolysis – Succinylcholine
• recommended for initial airway management

– Vecuronium
• treatment of choice for long term blockade

Treatment
• ANS dysfunction treatment
– Labetalol
• useful for treatment due to combined alpha and beta activity

– Magnesium sulfate
• inhibits the release of epinephrine and norepinephrine from the adrenal glands

– Clonidine
• central alpha receptor agonist for cardiac stability

Immunization
• Disease does not confer immunity so those that recover must undergo immunization • Tetanus toxoid – 0.5 cc IM at presentation, 6 weeks, and 6 months – Local reactions are common – Less common serous reactions include urticaria, anaphylaxis, or neurologic complications

Immunization and TIG guide
Clean, Minor wounds History of Td Doses Td TIG All other wounds Td TIG

Unknown or < 3 Three or more

Yes No

No No

Yes Yes

Yes No

• Td dose: 0.5cc IM • TIG dose: 250 U IM • DPT given if under 7, Td given if over 7

Rabies

Rabies
• Rabies ranks number 10 worldwide as a cause of mortality • 50,000 – 60,000 deaths annually worldwide

• Rare human cases in US but 35,000 people provided prophylaxis annually

Microbiology
• Lyssavirus genus prototype
– Single-stranded, negative-sense, nonsegmented RNA

• 7 rabies groups in genus
– Classic rabies virus – common rabies – 6 others with less than 10 reported human cases of disease

Pathophysiology
• Virus course
– Initial uptake of virus by monocytes in 48-96 hours – Crosses motor end-plate to travel up the axon to the dorsal root ganglia to the spinal cord and the CNS – Then spreads outward via peripheral nerves to infect almost all tissue of the body

Pathophysiology
• Histologically resembles other encephalitis – Monocellular infiltration with focal hemorrhage – Demyelination
• Perivascular gray matter • Basal ganglia • Spinal cord

• Negri bodies – Eosinophilic intracellular lesions in cerebral neurons – Highly specific for rabies – Present in 75% of rabies cases

Negri bodies

Epidemiology
• Primarily a disease of animals • Human cases reflect the prevalence in animals and degree of human contact with them • Major vectors include – Dogs – Foxes – Raccoons – Skunks – Coyotes – Mongooses – bats

Epidemiology
7,369 cases of animal rabies in the US in 2000 • Wild animals (93%)
– – – – – Raccoons (37.7%) Skunks (30.2%) Bats (16.8%) Foxes (6.2%) Others (2.2%)

• Domestic animals (7%)
Cats (3.4%) Dogs (1.6%) Cattle (1.1%) Horses, donkeys, mules (0.71%) – Sheep, goats, camels (0.15%) – Others and ferrets (0.06%) – – – –

Epidemiology
• Dogs – Less than 5% of animal cases in US, Canada and Europe – Greater than 90% of animal cases in developing countries • Very rare documented rabies in: – Squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice, domesticated rabbits and other small rodents – Almost never requires post exposure prophylaxis

Epidemiology
• Transmission
– Saliva though bite of an rabid animal most common – Aerosolized in bat caves – Mucus membrane transmission also reported

• Bites and scratches
– Risk of developing rabies dependant on the location injury, depth, an number of bites

Infection Risk
• Risk of infection Multiple bites around the face
Single bite Superficial bite on the extremity Contamination of open wound by saliva Transmission via fomites (e.g. tree branch, or animal) 80-100% 15-40% 5-10% 0.1% 0%

Epidemiology
• 32 cases reported from 1980 to 1996 in the US
– 7 had a known animal bite
• 6 dog bites in a foreign country • 1 bat bite

– Animal contact identified in 12
• • • • 8 2 1 1 with with with with a a a a bat dog cow cat

– No identifiable source in the other 13

Preexposure Prophylaxis
• Prophylaxis
– Individuals with occupations or recreation that place them at risk should receive the series – 4 shot series with booster shots required – Does not eliminate need for postexposure prophylaxis
• No need for HRIG and less doses of vaccine

Postexposure Prophylaxis
 Indicated for all persons possibly exposed to a rabid animal  Exposure is a bite, scratch, abrasion, open wounds, or mucous membrane exposure  Contact alone, and contact with blood, urine, or feces does not constitute and exposure  Cleansing wound with 20% soap and water has been show in experimental animals to markedly reduce the rate of infection

Bats
• Increasingly important wildlife vectors of transmission of rabies • All cases of possible bat bites the bat should be collected and tested for rabies

• Bat unavailable
– Begin postexposure prophylaxis

Dogs, Cats, and Ferrets
• Observation
– CDC recommends 10 days of observation of a healthy dog, cat, or ferret after a bite – Normal behavior
• No action needed

– Unusual behavior
• Sacrifice animal, test for rabies, and initiate HRIG and vaccine
– Positive – Complete course of vaccine – Negative – Discontinue course

Possible animal exposure Carnivore, bat or salivary exposure Bird, reptile, rodent or nonsalivary exposure Bat, skunk, raccoon, cow, bobcat, coyote, or fox Captured No Vaccine needed

Dog or cat

Captured and quarantined Sacrifice and test Initiate vaccine +HRIG

Normal behavior 10 days

No vaccine needed

Rabid Vaccine +HRIG Not Rabid Discontinue vaccine

Strange behavior Sacrifice, initiate vaccine and HRIG Rabid Vaccine + HRIG Not Rabid Discontinue vaccine Escaped No epidemiologic prevalence in area No vaccine needed

Escaped

Vaccine + HRIG

Epidemiologic prevalence

Vaccine +HRIG

Bat, skunk, raccoon, cow, bobcat, coyote, or fox

Captured and quarantined

Escaped

Sacrifice and test Initiate vaccine +HRIG

Vaccine + HRIG

Rabid Vaccine +HRIG

Not Rabid Discontinue vaccine

Dog or cat

Captured Normal behavior 10days

Escaped No epidemiologic prevalence in area

No vaccine needed

No vaccine needed
Epidemiologic prevalence

Strange behavior Sacrifice, initiate vaccine and HRIG

Vaccine +HRIG

Rabid Vaccine + HRIG Not Rabid Discontinue vaccine

Postexposure Prophylaxis
• Course
– HRIG (human rabies immune globulin)
• • • • One dose initially May be given up to 7 days after an exposure Infiltrate as much as possible around wound Give on the opposite side as the vaccine

– Vaccine
• 5 doses over 28 days

Postexposure Prophylaxis
• Vaccine reactions
– Minor reaction
• Erythema, swelling, pain • 30-74%

– Systemic reaction
• Headache, nausea, abdominal pain, muscle aches • 5-40%

– Anaphylaxis and neurological symptoms
• Rarely reported

• Vaccine should not be stopped for minor or systemic reactions

Special Circumstances
• Prior rabies immunization
– Either prior preexposure course or full postexposure course – No HRIG – Course shortened to 2 doses
• One dose on presentation • One dose three days later

Special Circumstances
• Immunocompromised patient
– HRIG and vaccine usual course – Safe
• Vaccine is inactivated so no danger of contracting

– Stop all immunosuppressives if possible – Measure antibody titers to assure appropriate response

Special Circumstances
• Travelers
– Preexposure prophylaxis
• Recommended if prevalence and possible exposure • Veterinarians, animal handlers, spelunkers, certain lab workers

– Non-FDA postexposure prophylaxis
• If initiated in another country contact health department for recommendations

Special Circumstances
• Pregnancy
– No adverse effects of the vaccine or HRIG – Follow usual course in pregnancy if indicated

Special Circumstances
• Children
– Vaccine
• Same dose and same course

– HRIG
• Dose is based on weight • If quantity of HRIG not sufficient to infiltrate all wounds may be diluted with saline

Clinical Disease
 Incubation period  20 to 90 days  4 days up to 19 years have been reported  Greater than 1 year is well documented  Prodrome  Fever, sore throat, chills malaise, headache, N/V, weakness  May report limb pain, weakness, and paresthesias  Nonspecific neurologic conditions such as anxiety, agitation, irritability or psychiatric disturbances

Clinical Disease
• Acute neurologic phase
– Furious – 80%
• Hyperactivity, disorientation, hallucinations, bizarre behavior • Symptoms may alternate with calm • Autonomic dysfunction • Hydrophobia with pharynx spasms in 50%

– Paralytic – 20%
• Paralysis in the extremity, diffuse or ascending • Fever and nuchal rigidity

Clinical Disease
• Coma
– Almost always present within 10 days

• Death
– Occurs from complications such as pituitary dysfunction, seizures, respiratory dysfunction, cardiac dysfunction, ANS dysfunction, ARF, or infection – Outcome almost always fatal – No person without post-exposure prophylaxis in the US has survived since 1980

Diagnosis
• Rabies should be in the differential of any acute encephalitis • May be confused with poliomyelitis, Guillain-Barre syndrome, transverse myelitis, postvaccinial encephalomyelitis, CVA, atropine-like poisoning, other viral encephalitis

Diagnosis
• Lab testing
– No one test is completely informative – Test serum, CSF, and skin for antibodies in a non-vacinated person – Nuchal skin biopsy most sensitive early – PCR from saliva also useful

Treatment
• Limited
– No specific treatment exists for clinical course – Treatment directed at the clinical complications

AVIAN INFLUENZA

AVIAN INFLUENZA

Penyebab :
 Virus RNA, Fam. Orthomyxoviridae, Genus : Orthomyxovirus : tipe A, B dan C.  Tipe A : unggas, manusia, kuda, babi, mamalia lain  Tipe B dan C : manusia  Beramplop, 2 permukaan antigen: hemaglutinin (HA) dan Neuraminidase (NA)  HA : 15 macam, NA : 9 macam  Kombinasi keduanya hasilkan lebih dari 100 tipe virus.  AI patogenik : H5 dan H7, contoh : H5N1

AVIAN INFLUENZA
ILUSTRASI SEL VIRUS AI

AVIAN INFLUENZA
SIFAT VIRUS  Hemaglutinasi pada unggas  Peka terhadap panas, pH yg ekstrim  Kondisi non isotonis dan udara kering  Peka terhadap pelarut lemak, spt : deterjen  Daya infeksi rendah oleh : formalin, oksidator, β-propiolakton, iodine, larutan asam, eter, ion amonium dan klorida

AVIAN INFLUENZA
• Tahan dalam tubuh unggas sampai beberapa bulan • Dikeluarkan dari tbh penderita lewat : sekresi hidung, feses dan mata. • Dalam feses tahan thd usaha inaktiasi : pada suhu 0-40C tahan 30 -35 hari dan pada suhu 200C tahan 7 hari. • Mati pada pemanasan 600C selama 30 menit, 800C selama 1 menit • Mati karena deterjen, formalin, alkohol 70%

AVIAN INFLUENZA
• Teori antigenic shift dari antigen permukaan • Virus A: antigenic shift, B: antigenic drift, C: relatif stabil • Adanya organisme sebagai mixing vessel, misalnya babi • Sampai 5 Agustus 2005: 112 kasus A pada manusia(H5N1) di Hongkong, Vietnam, Thailand, Kambodia dan Indonesia

AVIAN INFLUENZA
CARA PENULARAN  Kontak langsung  Tidak langsung ; udara tercemar oleh muntahan, feses atau droplet penderita  Feses yg mengandung virus bs mencemari : air minum, pakan, kandang, burung liar, pakaian, sepatu, peralatan, kendaraan, serangga.

AVIAN INFLUENZA
Sumber utama penularan :
1. Spesies lain dalam kelompok unggas domestik (dari itik ke ayam). 2. Burung eksotik yg dipelihara 3. Burung liar (migrasi burung air). 4. Hewan lain (kalkun dapat tertular dari babi)  Tidak ada indikasi penularan secara vertikal.

MANIFESTASI KLINIS
• • • • • • Inkubasi: 3 hari (2-4 hari) Sistem respirasi : ringan s/d berat ILI: influenza-like Ilness Batuk, pilek, demam Cephalgia, odynophagia, myalgia, malaise Berat: Pneumonia s/d ARDS (progresif dan fatal) • Lab: lekopenia, limfopenia, trombositopenia • CXR: progresif

DIAGNOSIS
• • • • • • • Uji konfirmasi: Kultur dan identifikasi H5N1 Real Time PCR Serologi: IFA, Netralisasi (kenaikan titer 4x) Uji penapisan: Rapid test, HI, ELISA Lab lain : DL, AST/ALT, Ureum/Creatinine, BGA Radiologis

OBSERVASI
Panas >380C disertai 1 atau lebih: - Batuk - Odynophagia - Pilek - Nafas pendek/sesak nafas - Pneumonia Belum jelas ada tidaknya kontak dengan unggas sakit/mati mendadak yang belum diketahui penyebabnya dan produk mentahnya Px diobservasi klinis, epidemiologis dan pemeriksaan lab

SUSPECT
Panas >380C disertai 1 atau lebih: - Batuk - Odynophagia - Pilek - Nafas pendek/sesak nafas - Pneumonia Disertai 1 atau lebih: - Pernah kontak dengan unggas sakit/mati mendadak yg tidak diketahui sebabnya dan produk mentahnya dalam 7 hari terakhir sebelum gejala - Pernah tinggal di daerah yg terdapat kematian unggas yg tidak biasa dalam 14 hari - Kontak dg penderita AI terkonfirmasi dalam 7 hari - Pernah kontak dg spesimen AI dalam 7 hari - Lekopenia ≤ 3000 - Titer antibodi dg HI test menggunakan eritrosit kuda atau ELISA untuk influenza A tanpa subtipe ATAU Kematian akibat ARDS dengan 1 atau lebih: - Lekopenia atau limfopenia dengan/tanpa trombositopenia

PROBABLE
Kasus suspek + 1 atau lebih: - Kenaikan titer AB minimum 4x terhadap H5 dg HI test menggunakan eritrosit kuda atau ELISA test - Hasil lab terbatas untuk influenza H5 menggunakan netralisasi test (ref lab) - Dalam waktu singkat menjadi pneumonia berat/gagal nafas/meninggal dan tidak terbukti ada penyebab lain

CONFIRMED
Suspect atau probable + 1 atau lebih: - Kultur virus poditif - PCR positif - IFA test positif dg antibodi monoklonal H5N1 - Kenaikan titer antibodi spesifik terhadap H5N1 sebanyak 4x pada paired serum sample dengan uji netralisasi

HIGH RISK
• Pekerja peternakan/pemrosesan unggas • Pekerja lab yang memproses sample paien/unggas yang terjangkit • Pengunjung peternakan/pemrosesan unggas (7 hari) • Pernah kontak dg unggas sakit/mati mendadak belum diketahui sebabnya dan atau babi serta produk mentahnya dalam 7 hari • Pernah kontak dengan penderita AI dalam 7

KRITERIA RAWAT
• Suspect dg gejala klinis berat: Sesak nafas dengan gangguan frek nafas ≥ 30x/menit, Nadi ≥ 100x/menit, ada gangguan kesadaran, kondisi umum lemah • Suspect dengan lekopenia • Suspect dengan gambaran radiologis pneumonia • Kasus probable dan confirmed

TATALAKSANA
• • • • • Supportif: Bed rest, imunomodulasi Antiviral Antibiotik Respiratory care Antiinflamasi

ANTIVIRAL
• Paling efektif diberikan dalam 48 jam pertama • Suspect: oseltamivir 2x75 mg 5 hari, simtomatik dan antibiotik bila ada indikasi • Probable: Oseltamivir 2x75 mg 5 hari, broad spectrum Ab, steroid bila ada indikasi, ICU (respiratory care) • Profilaksis: Oseltamivir 1x75 mg 7 hari s/d 6 minggu • Alternatif: Zanamivir