Public health officers C1

Tetanus
 introduction
• Tetanus is an acute disease manifested by
skeletal muscle spasm and autonomic nervous
system disturbance.
• It is caused by potential neurotoxin produced
by C.tetani.
• Vaccine preventable
• Occurs word wide where vaccine coverage is
low.
 Tetanus definition
• Case Definition CDC:
– “An acute illness with muscle spasm or hypertonia in the
absence of a more likely diagnosis” is probable tetanus.
– “ an illness occurring in a child who has normally ability to
suck and cry in the first 2 days of life but loses these ability
between 3 to 28 days of life become rigid and has spasm”
(WHO neonatal tetanus definition)
• Etiology:
– C. Tetani a gram positive rods, anaerobic, spore forming
found in soil world wide also found in animal and human
feces.
 Mode of transmission
• Abrasion, laceration,
• puncture wounds
• Complicates chronic skin ulcers, abscess and gangrene
• Burns, surgery, body piercing ,drug abusers
• inappropriate cord care
• Circumcision
• In 20 to 30% however, no entry wound identified.
• The more deep the entry point the more worse the disease
 Epidemiology
• Tetanus is rare in developed countries
• Most cases occur in unvaccinated or
incompletely vaccinated individuals
• peoples >60 years old and those who inject
drugs are at risk
• Global incidence in children and adults is
unknown, as few countries have good
surveillance system.
 PATHOGENESIS
• Toxins binds to peripheral motor unit terminal and axons
• Tetanus toxin(tetanospasmin) is transported intra- axonal to
motor nuclei of cranial nerves or ventral horns of the spinal
cord.
• Intramural transmissions blocks release of GABA at
presynaptic terminal
• At NM junction blocks release of inhibitory neurotransmitters
which causes unregulated transmitters release and spasm.
 Clinical forms
– Generalized including neonatal tetanus
– Localized
– Cephalic
 Clinical presentation
• Incubation period: 1 day-2 month
• Period of onset: 1-7 days
• Increased tone in the masseter muscle
– Trims or lock jaw
– Dysphagia, pain or stiffness in the neck
• Abdominal rigidity and stiff proximal limb muscles.
• Risus sardonicus-facial muscle
• Opisthotonos-back muscle
• Laryngeal spasm, cyanosis
• Fever, ileus, autonomic dysfunction
• Sudden cardiac arrest
 Complications
• Fracture
• DVT, PTE
• Muscle rapture and tendon avulsion
• Aspiration pneumonia
• Bed sore
• Rhabdomyolysis ,AKI
• Thrombophlebitis and VAP
 DDX
• Poisoning
• Hypokalemic tetany
• Alveolar abscess
• Drug dystonia
• Meningitis
• Generalized Peritonitis
 Treatment
• Principles
– 1. Eliminate the source of toxin
– 2. Neutralize the unbound toxin
– 3. Prevent muscle spasm
• General measures
– Respiratory support
– Nursing in quiet room and ICU
– Hydration and feeding
– Input and output monitoring
 Specific Rx
• Wound debridement
• Antibiotic-metronidazole 500 mg iv QID for 7days
• Antitoxin
– TAT 10,000 to 20,000 u im ( equine anti toxin)
– TIG 3000-6000 u im ( the human)
• Control spasm
– Diazepam , chlorpromazine 6 hrly
– Barbiturates , succinyl choline,Mgso4
 Prognosis
Adult Poor prognostics indicators
• Age >70, temperature >38.5
• Short IP<7 Days
• Puerperal, IV, postsurgery,
burn entry site
• Period of onset <48 h
• Heart rate >140 beats/minb
• Systolic blood pressure >140
mmHgb
• Severe disease or spasms
Neonatal
• Younger age, premature
birth
• Incubation period <6 days
Delay in hospital admission
• Grass used to cut cord
• Low birth weight
• Fever on admission
 Prevention
• Tetanus is prevented by good wound care and
immunization.
• Neonatal tetanus is preventable by
appropriate cord care and maternal
vaccination.
 Anthrax
• Anthrax may be the prototypic disease of bioterrorism
• causes disease in herbivores such as cattle, goats, and sheep.
• Anthrax spores can remain viable for decades.
• The remarkable stability of these spores makes them an ideal
bioweapon, and their destruction in decontamination
activities can be a challenge.
 Microbiology
• Anthrax is caused by B. anthracis
• gram-positive, nonmotile, spore-forming rod that is found in
soil.
• human infection is generally the result of contact with
anthrax-infected animals or animal products such as goat hair
in textile mills or animal skins used in making drums.
• Suggested that as few as one to three spores may be
adequate to cause disease
 Clinical forms
• Cutaneous anthrax : acquired by contact
• Inhalational anthrax : by inhalation
• GI anthrax : ingestion
Cutaneous anthrax
 Cont.
• The lesion of cutaneous anthrax typically begins as a papule
following the introduction of spores through an opening in
the skin. This papule then evolves to a painless vesicle
followed by the development of a coal-black, necrotic eschar.
• It was 20% fatal before availability of ABCs.
Papule,vesicle,ulcer,coal black, necrotic eschar
 Inhalational anthrax
• Responsible in the setting of bioterrorist attack. It occurs
following the inhalation of spores that become deposited in
the alveolar spaces.
• These spores are phagocytized by macrophages and
transported to the mediastinal and peribronchial lymph nodes
where they germinate, leading to active bacterial growth and
elaboration of the bacterial products edema toxin, protective
Ag and lethal toxin.
 Inhalational…
• Subsequent hematogenous spread of bacteria is accompanied
by cardiovascular collapse and death.
• The earliest symptoms are typically a viral-like prodrome with
fever, malaise, and abdominal and/or chest
symptoms(cough,SOB..) that progress over the course of a few
days to a moribund state.
• Characteristic findings on chest x-ray include mediastinal
widening and hemorrhagic pleural effusions,infiltrates
• Although initially thought to be 100% fatal, the experiences at
Sverdlovsk in 1979 and in the United States in 2001 indicate
that with prompt initiation of antibiotic therapy, survival is
possible.
 GI anthrax
• Less common
 DX
• Clinical
• Contact Hx
• G-stain
• Culture
• PCR
 Treatment
• Rapid diagnosis and prompt initiation of antibiotic therapy are
key to survival.
• Antibiotics
• penicillin, ciprofloxaciline, and doxycycline are DOC.
But clindamycin
and rifampin also have in vitro activity against the organism
. Antitoxin : Raxibacumab
 Prevention and vaccination
• AVA : the single vaccine licensed for human use is a product
produced from the cell free culture supernatant of an
attenuated, non capsulated strain of B. anthracis (Stern
strain), referred to as anthrax vaccine adsorbed (AVA).
• RPA( recombinant protective antigin) is on clinical trial
• PEP : two wks AVA with ciprofloxaciline,or 60 days of
ciprofloxaciline
 Brucellosis
• Definition:
• Brucellosis is a bacterial zoonosis transmitted directly or
indirectly to humans from infected animals,
predominantly domesticated ruminants and swine.
• The disease is known as undulant fever because of its
remittent character.
• Although brucellosis commonly presents as an acute
febrile illness, its clinical manifestations vary widely, and
definitive signs indicative of the diagnosis may be lacking.
 ETIOLOGIC AGENTS

• B. melitensis: sources are goats, sheep and camels

• Is the most common cause of symptomatic disease in
humans.
• B. abortus, is acquired from cattle or buffalo
• B. suis, from swine
• B. canis from dog
• B. Ovis cause disease in sheep
 Etiology cont..
• All brucellae are small, gram-negative, unencapsulated,
nonsporulating rods or coccobacilli
• They grow aerobically on peptone-based medium incubated
at 37°C; the growth of some types is improved by
supplementary CO2.
• In vivo, brucellae behave as facultative intracellular parasites.
• The organisms are sensitive to sunlight, ionizing radiation, and
moderate heat; they are killed by boiling and pasteurization
but are resistant to freezing and drying. Their resistance to
drying renders brucellae stable in aerosol form, facilitating
airborne transmission
 Cont.
• The organisms can survive for up to 2 months in soft
cheeses made from goat’s or sheep’s milk; for at least 6
weeks in dry soil contaminated with infected urine, vaginal
discharge, or placental or fetal tissues; and for at least 6
months in damp soil or liquid manure kept in cool dark
conditions.
• Brucellae are easily killed by a wide range of
common disinfectants used under optimal conditions but
are likely to
be much more resistant at low temperatures or in the
presence of heavy organic contamination.
 Epidemiology
• The true global prevalence of human brucellosis is
unknown because of the imprecision of diagnosis
and the inadequacy of reporting and surveillance
systems in many countries.
• Recently, there has been increased recognition of the
disease in
• Mediterranean countries, china
• western, central, and southern Asia
• Africa/ kenya, uganda
• South and Central America
 Modes transmission
• animal contact through inhalation of organisms is the
most frequent cause of infection, and affects
herdsmen, dairy-farm workers, and laboratory
workers
• Ingestion of untreated milk or its products, or raw
meat is a common route
• Brucella melitensis is biological warfare or
bioterroristic agents which can be released as
aerosols
• Dairy products: soft cheeses, unpasteurized milk, and ice
cream, are the most frequently implicated sources of infection
• raw meat Penetration of intact or abraded skin is a common
route of infection among abattoir workers in developing and
developed countries.
• Accidental autoinoculation or conjunctival splashing of live
brucella vaccine during animal vaccination among veterinarian
• Trans placental transmission
• breast feeding
• Sexual transmission
 Immunity and Pathogenesis

• both humeral and cell-mediated immune responses

 Humeral immunity
• Antibodies promote clearance of extracellular brucellae
• facilitation of phagocytosis by polymorphonuclear and
mononuclear phagocytes
• antibodies alone cannot eradicate infection
• Organisms persistent intracellular infections taken up by
macrophages and other cells can establish The key target cell
is the macrophage
• Tumor necrosis factor (TNF-) stimulates cytotoxic lymphocytes
and activates macrophage
• interleukin (IL) 12 , IFN : TH1-type responses and stimulates
macrophage activation
• IL-4, IL-6, and IL-10 :Th2 down regulate the protective
response
 The incubation period
• varies from 1 week to several months
• Acute or chronic presentations
 Clinical manifestations
• Brucellosis almost invariably causes fever, profuse sweats,
especially at night
• fever has undulating pattern
• associated with musculoskeletal symptoms and signs in about
one-half of all patients
• Undulant- rising & lowering
• Brucellosis- fever- undulating
• - profuse sweats
 Cont.
• B. melitensis tends to be associated with a more acute and
aggressive presentation
• B. suis with focal abscess induction
• B. abortus infections may be more insidious in onset and
more likely to become chronic
 Cont.
three patterns:
• 1. febrile illness that resembles typhoid but is less severe
• 2.fever and acute monoarthritis, typically of the hip or knee,
in a young child
• 3. long-lasting fever, misery, and low-back or hip pain in an
older man.
 Cont.
• In an endemic area the Middle East
a patient with fever and difficulty walking into the clinic would
be regarded as having brucellosis until it was proved otherwise.
 Cont.
• apathetic and fatigued
• lose appetite and weight
• myalgia, headache, and chills
• febrile illness that resembles typhoid
• fever and acute monoarthritis, typically of the hip or knee, in
a young child
• long-lasting fever, misery, and low-back or hip pain in an
older man.
 Cont.
• Osteomyelitis more commonly involves the lumbar and low
thoracic vertebrae

• septic arthritis are the knee, hip, sacroiliac, shoulder, and

sternoclavicular
monoarthritis or polyarthritis
Osteomyelitis may also accompany septic arthritis
 1.spondylitis
• anterior erosions of the superior end plate
• sclerosis of the whole vertebra
• Anterior osteophytes
• vertebral destruction or impingement on the spinal cord is
rare
Spondylitis
 2.pulmonary
• 25% of patients have a dry cough,
• Pneumonia
• Empyema
• lung abscess
• Intrathoracic adenopathy
 3.Gastrointestinal

• 25% hepatosplenomegaly
• Tonsillitis
• hepatitis
• splenomegaly
• Mesenteric lymphadenopathy with abscess formation,
cholecystitis, peritonitis, pancreatitis
• The liver transaminases, alkaline phosphatase, and serum
bilirubin may be mildly raised.
 4.lymphoglandular
• 10–20% have significant lymphadenopathy
the differential diagnosis
1.Tbc
2.Epstein-Barr virus
3.Toxoplasma
4.Cytomegalovirus
5.HIV
 5.genitourinary
• 10% of men have acute epididymoorchitis
• Prostatitis
• Salpingitis
• pyelonephritis
• Fetal loss among infected pregnant women
• seminal vesculitis
 Cont.
• dysmenorrhea, amenorrhea
• tubo-ovarian abscesses, chronic salpingitis, and cervicitis.
• Renal granulomatous lesions with abscess formation, with
caseation
• posterior urethritis.
• Urine culture may be positive in about 50 per cent of patients
with brucellosis.
 6.Neurobrucellosis
• Neurologic involvement is common
• depression and lethargy
• lymphocytic meningoencephalitis that mimics
neurotuberculosis or noninfectious conditions
• intracerebral abscess, a variety of cranial nerve deficits, or
ruptured mycotic aneurysms.
 DDX

• multiple cerebral or cerebellar abscesses

• ruptured mycotic aneurysm
• cranial nerve lesions
• transient ischaemic attacks-TIA
• Hemiplegia,paraplegia
• myelitis radiculoneuropathy
• Neuritis
• Guillain–Barré syndrome
• Sciatica
• granulomatous myositis,
• rhabdomyolysis.
 7.Cardiovascular

• 1%
• Aortic valve-nature, prosthetic
• Endocarditis—leading cause of death
• Myocarditis
• Pericarditis
• aortic-root abscess
• mycotic aneurysms, thrombophlebitis, and pulmonary
embolism.
• blood culture extended for a period of up to 6 weeks.
 Diagnosis

• hepatic enzymes and bilirubin may be elevated.

• Peripheral leukocyte counts are usually normal or low, with
relative lymphocytosis
• Mild anemia may be documented
• Thrombocytopenia and disseminated intravascular
coagulation
• The erythrocyte sedimentation rate and C-reactive protein
levels are often normal but may be raised.
 Biopsy
• lymph node or liver may show noncaseating granulomas

• The radiologic features:

bony disease develop late and are much more subtle with less
bone and joint destruction
• Isotope scanning is more sensitive than plain x-ray
 Bacteriology
• Isolation of brucellae from blood, CSF, bone marrow, or joint
fluid or from a tissue aspirate successful in 50–70% of cases
• Very dangerous

PCR: The peripheral blood

• more sensitive and is certainly quicker than blood culture
• it does not carry the attendant biohazard risk posed by
culture
 serology
• In acute infection, IgM antibodies appear early and are
followed by IgG and IgA.
• All these antibodies are active in agglutination tests
• As the disease progresses, IgM levels decline, and the avidity
and subclass distribution of IgG and IgA change.
 For chronic brucelosis
• the complement fixation test
• Coombs' antiglobulin test
• enzyme-linked immunosorbent assay(ELISA
 Diagnostic clues
• in the patient's history include travel to an endemic area
• employment in a diagnostic microbiology laboratory
• consumption of unpasteurized milk products (including soft
cheeses)
• contact with animals
• a history of similar illness in the family (documented in almost
50% of cases).
 Treatment

• At least dual therapy required

• For adults with acute nonfocal brucellosis a 6-week course

• Complex or focal disease necessitates 3 months of therapy
• The "gold standard" for the treatment in adults is
streptomycin 0.75–1 g daily for 14–21 days + doxycycline 100
mg twice daily for 6 weeks
• relapse follows such treatment in 5–10% of patients
 Alternatives
• rifampin 600–900 mg/d + doxycycline 100 mg twice daily for
6 weeks.
• The relapse/failure rate is ~10% -20%
 in children, pregnant women

 TMP-SMX twice daily + rifampicine for 6 weeks

 Neurobrucelosis
• requires prolonged treatment ( for 3–6 months)
• with ceftriaxone +TTC+STM

 Brucella endocarditis
• three drugs
aminoglycoside + tetracycline + rifampin ± ceftriaxone
for 6 months
• Surgery
 Renal impairment
• Doxycycline +rifampicin

 Response to treatment:
Patients become afebrile
• other constitutional symptoms greatly improve within 4 to 14
days
• The liver and spleen become impalpable within 2 to 4 weeks.
• risk of Jarisch–Herxheimer reaction(JHR)
• Follow-up of clinical, blood culture, and serological tests
should be done every 3 to 6 months for 1 to 2 years
 Prognosis and Follow-Up
• Relapse occurs in up to 30% of poorly compliant patients.
• Thus patients should ideally be followed clinically for up to 2 years
to detect relapse
• The general well-being and the body weight of the patient are
more useful guides than serology
• IgG antibody levels detected by the SAT and its variants can remain
in the diagnostic range for >2 years after successful treatment
• Complement fixation titers usually fall to normal within 1 year of
cure
Immunity is not solid; patients can be reinfected after repeated
exposures
• Fewer than 1% of patients die of brucellosis
• death is usually:- cardiac
-severe neurologic disease.

Prevention:
• Vaccines based on live attenuated Brucella strains
• active immunization of animals
• pasteurization of all milk products before consumption is sufficient to
prevent