MODULE: Jaundice

VIRAL HEPATITIS:
- Systemic disease
- Affects hepatocellular function.
- Common cause of cholestasis in childhood

HEP VIRUS FAMILY GENOM MOT IP (days) ONSET Fulminant Cirrhosis Chronicity Carrier Serology (MRS) Management
E (harrisons) hepa and
(Har.) Hepatoma

A HAV Picornaviridae ssRNA Fecal-oral; 15-45 Acute 0.1% NO NO NO anti HAV IgM – Acute (active disease) o Supportive
parenteral(unusual) (30) anti HAV IgG – Chronic (old; no active o Immunoglobulin
sexual
dse; protected against repeated infection
2-6wks
B HBV Hepadnaviridae dsDNA Blood(products); 30-180 Insidious 0.1 -1% YES Occasional YES HBsAg - Disease (Acute or chronic) o Interferons alfa and pegylated-
enveloped percutaneous (60-90) or (1–10%) Anti-HBsAg - Immunity interferon alfa
[Contaminated
Acute
needles, razor (90% of o Nucleoside analogs [lamivudine,
4-25wks lgM anti-HBcAg = New infection
blades, neonates) adefovir, entecavir, &telbivudine]
toothbrushes], lgG anti-HBcAg = Old infection
sexual and o Nucleotide analog [tenofovir]
Vertical transmission HBeAg = High infectivity o combinations of the above
Anti-HBeAg = Low infectivity
C HCV Flaviviridae ssRNA Blood(products); 15-160 Insidious 0.1% (20%) Common YES [For all genotypes]
enveloped percutaneous (50) or Cirrhosis (85%) anti-HCV antibodies o Pegylated interferon
[Contaminated o Ribavirin
Acute
needles, razor [For genotype 1]
2-23wks YES
blades, o Pegylated interferon
toothbrushes], o Ribavirin
sexual and o Protease inhibitor (telaprevir or
Vertical transmission boceprevir)
D HDV Deltaviridae Defective Similar to 30-180 Insidious 5-20% YES Common YES Serology is not very helpful [detectable
RNA HBV and HCV o Supportive
(D agent) (60-90) or titers of lgM and lgG anti- HDV are present
5% - o Pegylated interferon
Acute only in a very short time]
[acute
ssRNA 4-25wks Same as
enveloped
HBV/HDV [Control of HBV infection is
co- that for currently the only way to
infection] HBV protect against HDV]

20% -
[superinfe
ction of
Invariable
chronic
HBV
infection]
E HEV Herpeviridae ssRNA Fecal-oral route, 14-60 Acute 1-2 % NO None NO o Supportive
principally via (40)
contaminated
water.
2- 8wks
F HFV Togalike-virus ? ? ? Acute ? ?

G HGV Flaviviridae ssRNA Transfusion and ? Acute Does not lead to liver
parenteral route disease
Hepatitis A (Enterovirus 72; Short incubation hepa”)
- Generally asymptomatic/ mild disease of childhood. o Blood count
- Endemic: early childhood w/ poor sanitation & Low SES  WBC
- Self-limiting hepatitis; anicteric hepatitis  may be normal or
 leukopenic with relative lymphocytosis
Etiology:  (there may be)Large atypical lymphocytes
o (+) ssRNA virus isolated from stool [characteristic of viral infection]
o GENUS: Enterovirus
o Spherical (diameter of 27mm) Management:
o NO lipid envelope (resistant to heat, alcohol and
fat solvent) o Supportive treatment:
o Resist heat at 60oc for 1 hour  Fluid maintenance and nutrition [small frequent
o Destroyed by: feeding]
 Autoclave (121oc for 20mins)
 Adequate PROTEIN and CARBOHYDRATES;
 Boiling (5mins)
 Dry heat (180oc for 1 hour)
minimum FAT
 UV rad (1.1 watt for 1min)  IVF therapy is occasionally necessary
 Formalin (1:4000 for 3 days)
 Chlorine (10-15ppm for 30 mins) Prevention:
Transmission: o Passive immunization (susceptible contacts)
o Fecal –oral route  0.02mL/kg
o Parenteral (in experimental animals) o Active immunization
o Vertical transmission is rare  Inactivated Hepa A vaccine

LIVER
Hepatitis B (Serum hepatitis; long incubation hepa”)
GI TRACT BILE FECES - Higher incidence in low SES
(Replicate in (Shed via bile
Cytoplasm of passage)
hepatocytes) Etiology:
o Incomplete circular dsDNA virus / partially dsDNA
o Complex structure of a core within a shell
 excreted in stool only for a short duration [only during
o The complete virion, also called a Dane particle
prodromal]
o Enveloped
 Maximal excretion: several days before clinical and
o Double shelled:
biochemical evidence of the disease
 Hepatitis B core antigen (HBcAg)
 The time patient seeks consult, viral load in feces has much
- Distinct antigenicity
reduced. [low nosocomial transmission]
 Hepatitis B surface antigen (HBsAg)
- Outer Shell
- Composed of carbohydrates, lipid and
Clinical manifestation:
protein Mostly in ASIA
- There are 4 subtypes (Adr, Adw, Ayr, Ayw)
Young children: Frequently mild or asymptomatic
Adult: More severe and Atypical HBsAg Acute infection
Carrier

Prodromal Phase: Anti-HBcIgM Appears early following infection

 ONSET: constitutional signs and symptoms [fever, HBeAg Degree of infectivity
headache, anorexia, lassitude/irritable, nausea
and vomiting, abdominal discomfort or pain] * if mother is(+)
 May be sudden or gradual - 100% baby will be infected
- 90% develop chronic hepa
Icteric Phase: (1-4 weeks) Antibodies: Demonstration of antibodies signifies
anti-HBc exposure to HBV
 Jaundice [appears after fever & other s/sx
subsides] anti-HBe
* disappearance of antigen and persistence
o Skin and sclera anti-HBs of antibodies signifies RECOVERY
o Progresses for few days, then slowly regresses
 Dark colored urine (order of * Absence of antibodies and persistence of
 Clay colored stool [at the height of jaundice] appearance) antigen for > 6months signifies chronicity of
 Hepatomegaly and tender hepatitis
 Splenomegaly [occasionally] HBV-DNA High degree of infectivity
 Nausea and vomiting and anorexia may continue
and/or become worse. Transmission:

Convalescence Horizontal transmission (person-to-person)

 Usually rapid and uneventful, without proceeding
to chronicity.
 Viremia is transient
 Complete resolution occurs [few develop
complication (cholestasis, relapsing hepatitis, etc.)]
 Fulminant hepatitis is VERY RARE
o Contaminated needles, razor blades, toothbrushes
o Blood transfusion/ blood products
o Percutaneous (skin cuts/abrasion)
o Orally [HBsAg is found in saliva, tears,
nasopharyngeal secretion, urine semen, and other
body fluids]

Diagnosis: Vertical transmission (mother-to-fetus)

o Presence of: o Influenced by e-marker (HBeAg) status of the
 anti HAV IgM – Acute infection (3-6months) mother
 anti HAV IgG – Chronic infection (years) o E-marker – reflects the infectivity of the carrier

o Transaminase studies: [AST and ALT]

 High (500-1000 units) Mother both HBsAg and HBeAg seropositive has 1.6
 Before and after onset of jaundice times higher risk for transmission than HBsAg
 Return to normal: 1 week after jaundice improve seropositive only
 In utero (5-10 %)
o Bile examination (in blood and urine)  Perinatal
 Increased SERUM bilirubin [both direct & indirect] o 8-10 % - during 1st - 2nd trimester
o Direct bilirubin may further rise as the o 67 % - during 3rd trimester
disease progress  Postpartum (even higher risk)
 In URINE urobilinogen decreases, bilirubin increases
 o NO teratogenic effect but increased risk for Management:
prematurity o Supportive treatment similar to HAV
Clinical manifestation: o Interferon alfa
 1.5million U/day IM x3/week for 3-6mons
o Acute cases[30-40%] present similar to Hepa A o Pegylated-interferon alfa
o Asymptomatic [60-70%] o Nucleoside analogs
 [lamivudine, adefovir, entecavir, &telbivudine]
o Nucleotide analog
90% - recover from infection  [tenofovir]
5-10% - progress to chronic hepatitis o Combinations of the above
1-2% - develops fulminant hepatitis [death 1-2 wks]
o Steroids
 Short courses with rapid withdrawal may be tried in
Factors the influence CHRONIC INFECTION: caution
o Younger age  Long term is NOT advisable
o Male sex [except Newborn, age takes precedence]
o Immunodeficiency Prevention:
o Homosexual males o Immunoprophylaxis
o Haemophiliacs
o Down syndrome Exposure Passive Active
HBIG IM HB vaccine IM
Perinatal 0.5mL 0.5mL
o Carriers are prone to develop cirrhosis [within 12hrs after birth] [from birth to 1wk]
o Active liver cell repair involving the T-lymphocytes and Percutaneous 0.06mL/kg 1mL IM
possibly the oncogenes [gene that has the potential to [within 24hrs] [0-1-6 months]
cause cancer] eventually lead to the development of Sexual 0.06mL/kg
HEPATOCELLULAR CARCINOMA (HCC) /HEPATOMA [within 24hrs]
(del mundo)

o The CDC recommends vaccination of all children 0 to

Diagnosis:
18 years of age
o Serological Examination: [all hepatitis has similar
o The vaccine also is recommended for all unvaccinated
manifestations and MOT may overlap, so serological exam is
adults who fall into one of the following categories:
the most accurate means of diagnosis]
 At high risk for infection by sexual exposure;
o Popular methods:
percutaneous or mucosal exposure to blood; and
 RIA (radioimmunoassay)
 Others
 ELISA ( enzyme-linked immunoassay)
o International travelers to regions with high
 Reverse passive hemagglutination
or intermediate levels of endemic HBV
infection
o Diagnosis depends on the presence of the SURFACE, CORE
o People with chronic liver disease
and E-ANTIGEN, their ANTIBODIES and HBV-DNA
o People HIV infection
Serology interpretation:
o All pregnant women be routinely tested for HBsAg
during an early prenatal visit and that infants born to
Time HBsAg Anti-HBs Anti-HBc HBeAg HBsAg positive mothers receive appropriate doses of
Incubation Period + - - + HBIG and hepatitis B vaccine
Acute infection + - +(IgM) +
Window period - - +(IgM) -
Complete recovery - + +(IgG) -
Hepatitis C (Parenterally transmitted non-A, non B hepatitis)
Chronic (Carrier) + - +(IgG) -
Chronic (Active) + - +(IgG) + Etiology:
o (+)ssRNA virus
Vaccinated - + - -
o With lipid envelope (60nm in diameter)
o Therefore sensitive to ether, alcohol & organic fat
* Persistence of HBsAg is the principal marker of risk for
developing chronic liver disease and liver cancer Transmission:
(hepatocellular carcinoma) later in life. o Parenterally by contaminated blood(products)
o Hemodialysis and IV drug abuse
o Sexually transmitted
o Vertical transmission [documented in 7%
seropositive mother]
 Risk of transmission correlates well with
maternal HCV-RNA titer.

Clinical manifestation:
o Relative UNCOMMON to children
o Clinical course overlap with HAV and HBV
o Progresses to cirrhosis and hepatoma [like HBV]
o LEADING CAUSE FOR LIVER TRANSPLANT

Diagnosis:
o Detection of HCV-RNA[earliest detectable marker
for HCV infection (as early as incubation period)]
 Most reliable marker for acute infection
 Persistence >6 months : Chronic
o ELISA
 Detect anti-HCV
 (+) anti-HCV [current or past infection]

o RIBA (recombinant immunoblot assay)

 2nd generation test for anti HCV detection
Management:
o Interferon therapy (del mundo) Metabolism of Bilirubin
 3million IU x3/week IM or SQ for 6months
- Liver secretes 700-1200mL of bile/day [for digestion]
[For all genotypes] (MRS)
o Pegylated interferon
o Ribavirin BILE:
[For genotype 1] (MRS) o alkaline, bitter-tasting, yellowish green fluid
o Pegylated interferon o contains:
o Ribavirin - Bile salts (conjugated bile acids) [required for the
o Protease inhibitor (telaprevir or boceprevir) intestinal emulsification and absorption of fats.]
- Cholesterol
- Bilirubin (a pigment)
Hepatitis D (Delta hepatitis) - Electrolytes
- Water
Etiology: o It is formed by hepatocytes and secreted into the
o Delta agent which is a defective RNA virus canaliculi.
o (-)ssRNA
o NO nucleocapsid but with outer (HBsAg) coat
o 35-47nm Enterohepatic circulation:
o Replicates ONLY when associated with HBV
[incomplete virus, in that is require the assistance of - Having facilitated fat emulsification and absorption,
HBV to replicate ] most bile salts are actively absorbed in the terminal
ileum and returned to the liver through the portal
Transmission: circulation for resecretion.
o Similar to HBV

Clinical manifestation:
o 2 serological patterns are observed for Hepa D.
 Coinfection with HBV are usually acute and
self-limited
 Superinfection or infection associated with
CHRONIC HEPA B carrier leads to Chronic HDV
infection [may proceed to cirrhosis and death]
o Fulminant hepatitis is RARE but compared to other
forms of hepatitis it is common in HDV infection
o MORE SEVERE than any other forms.

Management:
o Supportive management
o Interferon therapy [Chronic HDV]
Prevention:
o Hepatitis B vaccine [HDV cannot exist without HBV]

Hepatitis E (Enteric non A, non B hepatitis

Etiology:
o (+)ssRNA
o similar to calicivirus Bilirubin
o Without an envelope (27-30nm in diameter) - By-product of the destruction of aged RBC.
- It gives bile a greenish black color and produces the
Clinical manifestation: yellow tinge of jaundice.
o Same with HAV infection but Less common in
children and common in adolescent and young
adult
o Does not cause chronic liver disease
o No identifiable chronic carries state
o (unlike in HAV) HEV is devastating in pregnant
women
Diagnosis:
o Serologic marker (anti HEV IgM and anti HEV IgG)
Management:
o Supportive management
o Enteric Precaution

Hepatitis F
- Not yet fully elucidated
- Toga-like particle has been found in the liver of
patients

Hepatitis G

Etiology:
o Distantly related to Hepatitis C
o ssRNA
o Flavivirus family

Transmission:
o Transfusion and parenteral route

Clinical significance:
o Does not seem to be associated with a specific
liver disease and not a major cause of liver disease
in children
Bilirubin metabolism

RBC DESTRUCTION
(Macrophages “Kupffer cells”)
)

Hemoglobin

Heme Globin

Iron Biliverdin Amino acid pool

Iron + Transferrin Bilirubin Reutilized

(in plasma) (in macrophage)

Released in the plasma

Bone Marrow Bilirubin + Albumin

Stored in the Liver
(to make new RBC)

Unconjugated/ Free /Indirect

bilirubin

Unconjugated bilirubin
+ Glucoronic acid (sinusoid/LIVER)

Conjugated/direct bilirubin

Excreted with bile

Gallbladder Intestine (duodenum)

Direct bilirubin is deconjugated

by bacteria
(Distal ileum and colon)

Urobilinogen

Feces Urine
MODULE: Poor suck Clinical manifestation:
- MOST often GENERALIZED [may also be localized]
TETANUS - INCUBATION PERIOD: 2-14 days (Nel)
- Acute, spastic paralytic illness
- Called Lockjaw General tetanus:
- Trismus – masseter muscle spasm [half of the case]
Etiology: - [early symptoms] Headache, Restlessness, & Irritability
- Clostridium tetani - [Followed by] stiffness, difficulty chewing, dysphagia,
- Motile neck muscle spasm
- Gram positive, spore-forming
- OBLIGATE ANAEROBES - Sardonic smile “risus sardonicus”
- Habitat:  Results from intractable spasms of facial and
 Soil buccal muscles
 Alimentary tract of some animals - Opisthotonos
 Dust  Spasm reaches the abdominal, lumbar, hip,
- Drumstick or tennis racket appearance (spores) and thigh muscles

Arched posture of extreme hyperextension

of the body; head and the heels bent backward and
the body bowed forward with only the back of the
head and the heels touching the supporting surface

- Laryngeal and respiratory muscle spasm [can lead to

airway obstruction and asphyxiation.]
- Patient remain CONSCIOUS in extreme fear and pain
[Because tetanus toxin does not affect sensory nerves or
cortical function]
- SURVIVE boiling [autoclaving should be done] - Seizures - sudden, severe tonic muscle contractions with
- NOT a tissue invasive organism [instead it produced
- Fist clenching
toxin that causes illness ”tetanospasmin”]
- Lethal dose: ~ 10-5 mg/kg [2nd most poisonous to - Flexion
botulinum toxin] - Adduction of the arms and
- Hyperextension of the legs.
Epidemiology: [The smallest disturbance by sight, sound, or
- Most common forms touch may trigger a tetanic spasm]
 Neonatal /umbilical tetanus [kills approx.
- Dysuria and urinary retention [bladder sphincter spasm]
300,000 infants/year]
- Forced defecation
 Maternal tetanus [postpartum, postabortal or
postsurgical wound infection] - Fever (40oc) [substantial metabolic energy consumed
- Common Age group [ >60] by spastic muscles.]
- Autonomic effects: tachycardia, dysrhythmias, labile
Pathogenesis: hypertension, diaphoresis, and cutaneous
vasoconstriction.
Introduction of spores germinate
NEONATAL TETANUS
- Infantile form of generalized tetanus [typically manifests
within 3-12 days of birth]
Bacterial death & Multiply - Progressive difficulty in feeding (sucking & swallowing)
lysis - Associated hunger
- Crying

Release toxin - CHARACTERISTICS:

(tetanospasmin)  Paralysis or diminished movement, stiffness
and rigidity to the touch, and spasms, with or
Binds without opisthotonos
LOCALIZED TETANUS
Neuromuscular junction
- Painful spasms of the muscles adjacent to the wound
site and may precede generalized tetanus.

- CEPHALIC TETANUS
Motor nerve (endocytosis)  Rare form of localized tetanus
 Involves the bulbar musculature that occurs
with wounds or foreign bodies in the head,
nostrils, or face.
Retrograde axonal  [Characterized by: retracted eyelids, deviated
transport gaze, trismus, risus sardonicus, and spastic
paralysis of the tongue and pharyngeal
Exit spinal cord musculature.]

Adjacent spinal inhibitory

interneuron

Prevents the release of

GLYCINE and GABA

Muscles contracts and

cannot relax
Diagnosis:
- strictly clinical; no confirmatory laboratory tests
The WHO definition of adult tetanus requires at least one of
the following signs:
- Trismus (inability to open the mouth)or
- Risus sardonicus (sustained spasm of the facial
muscles); or
- Painful muscular contractions.
- NORMAL routine laboratory studies [Usually]
- Peripheral leukocytosis [may result from a secondary
bacterial infection of the wound or may be stress]
- CSF normal
- Increased ICP d/t intense contraction [possible]
- Electroencephalogram & electromyogram [shows NO
characteristic pattern]
- C. tetani is NOT always visible on Gram stain and is
isolated in only approximately 30% of cases.
Management: [requires]
1. Eradication of C. tetani and its conducive environment
- Wound excision & debridement
 Remove devitalized tissue that creates
anaerobic growth condition
 Done PROMPTLY after TIG & antibiotic admin.
 Excision of umbilical stump (neonatal tetanus)
is no longer recommended.
- Antibiotic therapy
(Penicillin G)
 DOSE : 100,000 units/kg/day
 FREQ/ ROUTE: divided q4-6 hr IV for 10-14 days
 [100,000–200,000 IU/kg/day IV, in 2–4 divided
doses(WHO) ]
 Antibiotic of choice [because of its effective
clostridiocidal action and its diffusibility, which
is an important consideration because blood
flow to injured tissue may be compromised.]
(Metronidazole)
 DOSE : 500 mg
 FREQ/ROUTE: every 8 hrs IV for adults [nelsons]
 FREQ/ROUTE: every 6 hrs IV or Oral [who]
(Erythromycin and tetracycline)
 alternatives for penicillin-allergic patients
 > 8 yr of age
2. Neutralization of all accessible tetanus toxin
- Administer TIG ASAP [to neutralize toxin that diffuses from
the wound into the circulation, BEFORE it binds to distant
muscle groups]
Tetanus toxin cannot be neutralized by TIG after it has
begun its axonal ascent to the spinal cord.
 Optimal dose has not been determined.
 500 units IM once is sufficient to neutralize
systemic tetanus toxin [but total doses as high
as 3,000-6,000 units are also recommended];
[IM or IV(WHO) ]
 Infiltration of TIG into the wound is now
considered unnecessary.
Alternatives:
 If TIG is not available, use IVIG as substitute
- IVIG contains 4-90 units/mL TIG
- Dosage not known
- Not approved for this indication
- Intrathecal TIG, given to neutralize
tetanus toxin in the spinal cord, is not
effective.
 Tetanus antitoxin (TAT)
- equine or bovine-derived
- usual dose: 50,000-100,000 units
- Given half IM and half IV [but as little
as 10,000 units may be sufficient.]
- 15% of patients experience serum
sickness [check for possible sensitivity]
- Administer Tetanus toxoid
 DOSE: 0.5 cc IM at a separate site.
 Episode of tetanus does not result in the
production of toxin-neutralizing antibodies so
active immunization is mandatory
[If NO history of primary TT vaccination, 2nd dose
should be given 1–2 mos after the 1st dose and a 3rd
dose 6–12 mos. later.]
3. Control of seizure
- All patients with generalized tetanus need muscle relaxants.
(Benzodiazepines)
- Provides both relaxation and seizure control.
Diazepam
Pedia
- DOSE: 0.1-0.2 mg/kg [initial]
- FREQ: q 3-6 hr given IV
[Is subsequently titrated to control the tetanic spasms,
after which the effective dose is sustained for 2-6 wk
before a tapered withdrawal.]
Adult
- DOSE: increments of 5 mg, IV
[While Lorazepam is given in 2 mg increments, titrating
to achieve spasm control without excessive sedation
and hypoventilation]
(Magnesium sulphate)
- Can be used alone or in combination with
benzodiazepines to control spasm and autonomic
dysfunction [morphine can be used as well]
- DOSE: 5 gm (or 75mg/kg) IV [loading dose],
Then 2–3 grams per hour until spasm control is achieved.
(Other drugs)
- Other benzodiazepines (midazolam), chlorpromazine,
dantrolene, and [baclofen- should only be used in ICU
setting ]
4. Airway and respiration
- Drugs used to control spasm and provide sedation can
result in respiratory depression. [If mechanical ventilation
is not available, patients must be carefully monitored.]
- Early tracheostomy is preferred [endotracheal tubes
and suctioning can provoke spasm and exacerbate
airway compromise]
5. Meticulous supportive care & palliation
- Place patient in a separate ward/location if possible
- Quiet shaded area and protected from tactile and
auditory stimulation as much as possible.
- Adequate fluids and nutrition should be provided.
[Tetanus spasms result in high metabolic demands and a
catabolic state. Nutritional support will enhance
chances of survival]
6. Prevention
- Serum antibody titer of ≥0.01 units/mL is considered
protective.
ACTIVE IMMUNIZATION:
- Begin in early infancy with combined
diphtheria toxoid–tetanus toxoid–acellular
pertussis (DTaP) vaccine
- Months 2,4,6 and 15-18
- Booster doses:
- 4-6 yr (DTaP)
- 11-12 yr (Tdap)
- Then at 10 yr intervals thereafter throughout
adult life with tetanus and reduced diphtheria
toxoid (Td).
2 mons – 6 yrs DTap
> 7 yrs (11-18yrs) Tdap
> 28 yrs Td
- pregnant women:
- 1 dose of Tdap (each pregnancy)
[preferably at 27-36 wk gestation/6-9
months]
 Clean, minor All other wounds*
wounds
HISTORY OF Tdap/Td TIG Tdap/ Td TIG
ABSORBED TETANUS
TOXOID
Uncertain or <3doses YES NO YES YES
3 or more doses NO NO NO NO

Yes, if 10 yr or Yes, if 5 yr or
longer since the longer since the
last TTCV dose last TTCV dose
* Such as, but not limited to, wounds contaminated with dirt, feces, and saliva; puncture
wounds; avulsions; wounds resulting from missiles, crushing, burns, and frostbite.

Complication:
- Aspiration (pneumonia) [may have begun before the
first medical attention was received.]
- Pneumothorax and Mediastinal emphysema [possible
risk after endotracheal intubation and mechanical
ventilation]
- Iatrogenic apnea [excessive use of muscle relaxant]
- Laceration (mouth or tongue); intramuscular
hematomas or rhabdomyolysis with myoglobinuria and
renal failure; long bone or spinal fractures. [d/t Seizure]

Prognosis:
- The most important factor that influences outcome is the
quality of supportive care.
- Mortality is highest in the very young and the very old.
- GOOD prognosis
- Long incubation period, absence of fever, and
localized disease.
- BAD prognosis
- Onset of trismus <7 days after injury and with
onset of generalized tetanic spasms <3 days
after onset of trismus.