9. Epidemyology GAS
Source: sick patients, or carries of
infection
Transmission: air-drop , person to
person contacts:
Season: spring-summer
10. Clinical Presentation
Rapid onset
Fever 39-40° C
Cervical lymphadenitis
Intense pain in the throat, hyperemia
pharynx and tonsils
Bright, purulent exudate coating the
tonsils or white patches on mucous of
the tonsil,
Swelling of the soft palate
11. Diagnostic GAS
Bacteriological method
Rapid tests: Latex-Agglutination,
agglutination
ELISA,
DNA hybridization, polymerase chain
reaction-exposure of DNA
12. Treatment GAS
Penicillin (oral, parenteral)
Cephalosporins 1-2 generation of
Macrolides
Duration of the therapy – 10 days
13. Diphtheria
Acute anthroponous disease, caused by
Gram(+) toxigenic bacillus
Corynebacterium diphtheria,
characterized by local fibrinous-
inflammation of the mucus and/or skin,
general intoxication and toxic
complications: myocarditis, polyneuritis,
nephrosis.
15. History
Throughout history, diphtheria was a leading
cause of death among children
Through the ages, several epidemics struck
Europe, and even the American colonies in the
18th century.
In 1921, there were 206,000 cases of diphtheria
recorded in the U.S., with 15,520 deaths.
More recently, in the 1990s, large outbreaks of
diphtheria occurred in Russia ,Ukraine and in
other the former of the Soviet Union countries
16. History
The diphtheria bacterium was first identified
in the 1880s.
In the 1890s, the antitoxin against
diphtheria was developed, with the first
vaccine being developed in the 1920s.
With the development and administration of
the diphtheria vaccine, the incidence of
diphtheria has decreased significantly
17. Epidemiology
The source of infection is sick person
and carrier
The way of transmission is respiratory
primarily during close contact.
The autumn-winter seasonably is
characteristic of diphtheria
Immunity after this disease isn’t
strong. Person may be sick repeatedly
18. Transmission
Diphtheria is primarily transmitted via
airborne respiratory droplets or by direct
contact with nasopharyngeal secretions or
skin lesions from infected people.
Rarely, it can be spread by objects
contaminated by an infected person.
Overcrowding and poor living conditions can
further contribute to the spread of
diphtheria
19. What type of bacteria cause
diphtheria?
Diphtheria is caused by toxin-producing
strains of the gram-positive bacillus
Corynebacterium diphtheriae. There are
four biotypes of the bacterium (gravis, mitis,
intermedius, and belfanti), and each differs
in the severity of disease it produces.
Nontoxigenic strains are usually responsible
for less severe diphtheria involving the skin
(cutaneous diphtheria).
20. Pathogenesis
1. In majority cases the Corynebacterium
diphtheria is an upper respiratory tract
disease.
2. The common sections where the bacterium
multiplies is at throat and nasopharynx
(common symptom is advance sore throat)
the bacterium can also spread around the
body by the blood circulation system
(lymph nodes).
21. Pathogenesis
Corynebacterium diphtheria is a bacterium
which produces toxin. This toxin has effects
on the membrane cells, by inhibiting cellular
protein synthesis.
It is also responsible for local tissue damage
and affects cell membrane structure.
Inflammation reaction to the toxin also has
an effect on the cell which results in tissue
necrosis.
22. Corynebacterium diphtheria
toxin
The toxin is 62,000-dalton polypeptide composed of
two parts which are A and B.
Part A fragment inhibits protein synthesis in
eukaryotic cells by catalyzing the NAD+-dependent
ADP-ribosylation of elongation factor.
Part B fragment facilitates delivery of fragment A
to the cytosol by binding to the cell surface
receptors
23.
24. Pathogenesis
Corynebacterium diphtheria can also cause
lesions and ulcers which are formed by
bacteria, fibrin and inflammatory cells
(pseudomembrane).
The lesions and ulcers are caused by the
toxin secretion which has an effect on the
cell membrane.
The pus which is produced by the bacterium
can also effect breathing by blocking
passage way with a coated pus which is
located at back of the throat
25. Pathogenesis
The toxin produced by Corynebacterium diphtheria
is absorbed by the membrane into the bloodstream
and distributed to the tissues of the body which
cause the symptoms of mild fever and chills.
Also, the infection Corynebacterium diphtheria can
cause the lymph glands to enlarge and swell to an
abnormal size.
This enlarge lymph will appear on the neck (both
sides of the neck) this is because Corynebacterium
diphtheria invades the lymph nodes which cause
them to inflame and harden
26. Pathogenesis
The toxin is liable for major problems which
are inflammation of the heart(myocarditis),
heart failure, and neuromyelitis optica
(nerve damage, paralysis).
It can also cause low platelet counts
(thrombocytopenia) and can also cause the
depletion of protein in the urine
(proteinuria).
27. Pathogenesis
The toxin secretion can also cause a
number of different diseases which include
necrosis of kidney tubules, cardiomyopathy,
thrombocytopenia and demyelination of
nerves .
The disease is caused in undeveloped
countries where people have poor health
styles and who are also susceptible (weak
immunity) and people who have not been
vaccinated.
28. Classification of
Diphtheria
Diphtheria of tonsils, mild form.
2. Diphtheria of tonsils, moderate form.
3. Diphtheria of tonsils, severe form.
4. Hypertoxic form of Diphtheria of tonsils.
5. Laryngeal diphtheria (diphtherial laryngotracheitis,
croup)
6. Nasopharyngeal diphtheria (diphtherial
nasopharyngitis, pharyngitis)
7. Diphtheria of anterior parts of the nose
8. Diphtheria other localization (skin, eyes)
9. Combined diphtheria
29. Symptoms
The symptoms of respiratory diphtheria usually begin
between two to five days after exposure to the diphtheria
bacterium (the incubation period). Symptoms of
diphtheria of tonsil may include the following:
Sore throat
Fever
Malaise
Hoarseness
Foul smelling nasal discharge
Headache
Cough
Difficulty swallowing
Difficulty breathing
30. Clinic
With the progression of diphtheria, the infected
individual may also develop an adherent gray
membrane (pseudomembrane) forming over the
lining tissues of the tonsils and/or nasopharynx.
This pseudomembrane is necrotic (dead) tissue that
develops from the effects of the diphtheria toxin.
Individuals with severe disease may also develop
neck swelling and enlarged lymph nodes of the
neck, leading to a "bull-neck" appearance.
Extension of the pseudomembrane into the larynx
and trachea can lead to obstruction of the airway
with subsequent suffocation and death.
31. Local features (pharynx)
Local inflammatory changes of the tonsils
are following:
- Mild hyperemia with cyanotic color,
- Edema of the pharynx and/or subcutaneous neck
tissue,
- Covers on the tonsils.
- Covers are of grayish-whitish color, hard to
remove, the mucus bleeds after removal.
- Regional lymphadenitis – edema and mild
tenderness of the cervical lymph nodes.
34. Systemic Symptoms
The dissemination of the diphtheria toxin to
the rest of the body can also lead to
systemic disease, causing complications :
Inflammation of the heart (myocarditis)
neurologic problems such as paralysis of
the soft palate, vision problems, and muscle
weakness.
Nephrosis
35. Cutaneous diphtheria
Cutaneous diphtheria is characterized
by a nonhealing skin ulcer covered by
a gray-brown membrane. It is typically
a localized infection that is rarely
associated with systemic complications
36.
37. How is diphtheria
diagnosed?
The diagnosis of diphtheria is confirmed by
isolation of the bacterium Corynebacterium
diphtheriae.
Diagnostic tests to isolate the bacterium
involve obtaining cultures from the nose and
throat in any individual suspected of having
diphtheria, as well as their close contacts.
38. Determining of toxin
production
It is also important to determine whether or not the
isolate from an infected person is capable of producing
diphtheria toxin, and this can be accomplished as well by
testing in specialized laboratories.
Finally, determining the patient's antibody levels to
diphtheria toxin can also be helpful for evaluating the
probability of the diagnosis of diphtheria and the potential
for severe illness.
Other tests, such as ECG, imaging studies, and blood
work can also help assess the extent of involvement of
the disease
39. Laboratory Diagnosis of the Diphtheria
А) Reaction of neutralization (Yensen method):
-Level of antitoxins ≤ 0,03 IUml → probable
Diphtheria;
-Level of antitoxins 0,05 to 0,4 IUml → Diphtheria can
not be excluded;
- Level of antitoxins ≥0,5 IUml (in first 5 days of the
disease) → Diphtheria is excluded
В) Reaction of direct hemagglutination (protective level ≥
1:320 (in first 5 days of the disease) – excludes Diphtheria
- Determination of diphtheria antitoxin level in blood
serum
- Molecular genetic methods (PCR) – determination of
the genetic material of phage producing toxin.
40. Report
Suspected or confirmed cases of
respiratory diphtheria should be
reported to your state health
department.
If cutaneous diphtheria is suspected,
samples from the skin can be obtained
and sent to specialized laboratories.
41. What is the treatment for
diphtheria?
If diphtheria is suspected in a patient,
prompt treatment should be undertaken
even before confirmatory lab results are
available. Patients should also be placed in
isolation to prevent further transmission of
the disease.
42. Antitoxin
Diphtheria antitoxin is the mainstay of therapy.
It neutralizes circulating diphtheria toxin and
reduces the progression of the disease.
The effectiveness of diphtheria antitoxin is
greatest if it is administered early in the course
of the disease.
The CDC can assist in obtaining the diphtheria
antitoxin. Antitoxin is not recommended for
asymptomatic carriers and it is usually of no
value in localized cutaneous diphtheria
43. Diphtheria antitoxin serum and antibiotics must be
used immediately, without waiting the results of
bacterial and serological investigations
Form of Diphtheria
First dosage of
serum
Way of
investigation
Mild diphtheria of
tonsils
40 – 60 thousand IU Intramuscular
Moderate diphtheria
of tonsils
80 - 100 thousand
IU
Intramuscular
Severe diphtheria of
tonsils,
hypertoxic or
combined forms of
diphtheria
120 – 150 thousand
IU
50% -
Intramuscular,
50% - intravenous
44. Antibiotics
Antibiotics should also be administered as soon as
possible to patients with suspected diphtheria.
Antibiotics help eradicate the bacteria, thereby
stopping toxin production, and they also help to
prevent transmission of diphtheria to close
contacts.
Penicillin and erythromycin are the recommended
antibiotics. Asymptomatic carriers, as well as all
close contacts potentially exposed to diphtheria,
also require antibiotic treatment.
Affected individuals are usually not contagious
after 48 hours of antibiotic administration.
45. Supportive measures
Supportive measures, such as
inserting a breathing tube (intubation),
may be necessary if the patient cannot
breathe on their own or if there is the
potential for airway obstruction.
Potential cardiac and neurologic
complications also need to be closely
followed and addressed in consultation
with the proper specialist.
46. Antibiotics
procaine penicillin G at a dosage of
600,000 units IM every 12 h until the
patient can swallow comfortably, after
which oral penicillin V is given at 125–250
mg four times daily to complete a 14-day
course;
Or erythromycin at a dosage of 500 mg IV
every 6 h until the patient can swallow
comfortably, after which 500 mg is given
PO four times daily to complete a 14-day
course.
47. Prevention
The person with diphtheria is excluded from school
until they have recovered and had two negative
throat swabs.
Contacts of the person with diphtheria are given
antibiotics and may also need to have a booster
vaccination with a diphtheria-toxoid containing
vaccine
Contacts who are children are excluded from early
childhood education, daycare, school and
community activities until throat swabs shown they
do not have the disease.
Adults who work with food or children are excluded
from their work until throat swabs shown they do
not have the disease.
48. Prophylaxis of Diphtheria
in close contacts
1. Determination of subjects of close contact
2. Medical observation during 7 days from the last
contact
3. Laboratory investigation: all the contacts are
performed cultures of throat and nose independent
of their vaccinal status
4. All the contacts are evaluated for the presence of
skin erosions and if present, cultures must be done
from skin erosions
5. At first signs of probable diphtheria in these patients
the antitoxic serum is indicated
49. Antibiotic prophylaxis in
contacts
Close contacts must receive
antibiotic prophylaxis
– prolonged penicillin intramuscular once (1,2
mln U);
– erythromycin – during 7–10 days (1 g/day)
2. All the carriers of toxigen strains of
C.diphtheriae must receive antibiotic
treatment
50. Immunization after
contact
1. All the contacts without complete course of
vaccination (that is, who received less than 3 doses
of anatoxin), should receive buster dosage of
vaccine, than should complete the vaccination
according to the vaccination schedule.
2. All the contacts with unknown vaccination history
should receive buster dosage of vaccine, than
should complete the vaccination according to the
vaccination schedule.
3. All the contacts with complete course of
vaccination, should also receive buster dosage of
vaccine, if vaccination was not performed within
the last 12 months.
51. Immunization against
Diphtheria
95% of children under 2 years of age should be
vaccinated by DPT.
Children of school age should receive buster immunization
with diphtheria anatoxin; 95% should be vaccinated
90% of adult population should be vaccinated with
preferentially DT every 10 years.
In case of diphtheria outbreak, all the adult population
should be vaccinated:
Clinical forms of diphtheria do not guarantee the
protective immune level → all the patients after
diphtheria should be vaccinated (Ukraine - after 6
months, USA - upon discharge from the hospital)
52. FACT:
Diphtheria can be prevented with a safe and effective vaccine.
Diphtheria can lead to breathing problems, heart failure,
paralysis, and sometimes death.
Nearly one out of every 10 people who get diphtheria will die
from it.
Most cases of diphtheria occur among unvaccinated or
inadequately vaccinated people.
Recovery from diphtheria is not always followed by lasting
immunity, so even those persons who have survived the
disease need to be immunized.