DIPHTHERIA

Diphtheria is an acute, toxin-mediated disease caused by Corynebacterium diphtheriae.

C. diphtheriae is an aerobic gram-positive bacillus. Only toxigenic strains can cause severe disease.
All isolates of C. diphtheriae should be tested by the laboratory for toxigenicity.
There are three biotypes gravis, intermedius, and mitis.
The most severe disease is associated with the gravis biotype, but any strain may produce toxin.

EPIDEMIOLOGY

The incubation period for respiratory diphtheria is typically 2 to 5 days and rarely up to 8 days.
Transmission may occur as long as virulent bacilli are present in discharges and lesions. The time is
variable, but organisms usually persist 2 weeks or less, and seldom more than 4 weeks, without antibiotics.

IMMUNITY

Treatment of diphtheria toxin with formaldehyde converts it to a nontoxic but immunogenic product
(diphtheria toxoid). Immunization with toxoid elicits antibody (antitoxin) that neutralizes the toxin and
prevents diphtheria.

Antitoxin neither prevents colonization by C. diphtheriae nor eradicates the carrier state.

Acquired immunity to diphtheria is due to primarily to toxin-neutralizing antibody (antitoxin). Most

young infants were immune because of transplacental transfer of maternal IgG antitoxin, but children
became susceptible by 6 to 12 months of age.
PATHOGENESIS

Susceptible persons may acquire toxigenic diphtheria bacilli in the nasopharynx.

The pathogenicity of C.diphtheria includes two phenomena:

1. Invasion of the local tissue of the throat, which requires colonozition and subsequent bacterial
proliferation.
2. Toxigenesis bacterial production of the toxin.

The C.diphtheria produces a toxin that inhibits cellular protein synthesis and is responsible for local
tissue destruction and membrane formation.
Blood plasma leaks into the area and fibrin network forms which is interlaced with rapidly-growing
C.diphtheria cells.
This membranous network covers over the site of local lesion and is referred to the as the
pseudomembrane.

The diphtheria bacilli do not tend to invade tissues below or away the surface epithelial cells at the
site of lesion.
At this site they produce the toxin that is absorbed and disseminated through lymph channels and
blood to the susceptible tissues of the body.
Degenerative changes in the tissues, which include heart, muscle, peripheral nerves, kidneys, liver
and spleen, result in the systemic pathology of the disease.

CLASSIFICATION

The disease is clinically classified according to the anatomical site of infection:

Pharyngeal
Tonsillar
Laryngeal
Nasal
Cutaneous.
 The form of tonsillar diphtheria is determinate by the extent of membrane.

Catarrhal (erythema of the pharynx without an exudate but with a culture positive for C.diphtheria)
Follicular (islands or patches of exudates in the posterior pharynx or tonsils)
Local (a membrane on tonsils)
Spread (a membrane covering all the tonsils and posterior pharynx)
Combined (describes more than 2 anatomic sites involved, including throat and skin).

Toxicity is determined by the extent of neck edema.

Nontoxic is defined as no edema or neck swelling.
Subtoxic is defined as swelling on one or both sides but limited to the submandibular area.
Toxic1 is defined as swelling midway down the neck,
Toxic 2 is defined as swelling down the clavicles,
Toxic 3 is defined as swelling and edema past the clavicles
Hypertoxic diphtheria as a profoundly ill cases with toxic shock.

PHARYNGEAL AND TONSILLAR DIPHTHERIA

The most common sites of infection are the tonsils and the pharynx.
Infection at these sites is usually associated with substantial systemic absorption of toxin.
Often by the time a physician is contacted, the membrane is greyish-green in color, or black if
there has been bleeding.
There is a minimal amount of mucosal erythema surrounding the membrane.
The membrane is adherent to the tissue, and forcible attempts to remove it cause bleeding.

ANTERIOR NASAL DIPHTHERIA

The onset is indistinguishable from that of the common cold and is usually characterized by a
mucopurulent nasal discharge (containing both mucus and pus) which may become blood-tinged.

A white membrane usually forms on the nasal septum. The disease is usually fairly mild because of
apparent poor systemic absorption of toxin in this location, and can be terminated rapidly by antitoxin and
antibiotic therapy.
 LARYNGEAL DIPHTHERIA

Laryngeal diphtheria can be either an extension of the pharyngeal form or the only site involved.
Symptoms include:
Fever
Hoarseness, (hoarse voice)
Barking cough

The membrane can lead to airway obstruction, coma, and death.

CUTANEOUS (SKIN) DIPHTHERIA

Skin infections are quite common in the tropics and are probably responsible for the high levels of
natural immunity found in these populations.
Skin infections may be manifested by a
scaling rash
ulcers with clearly demarcated edges and membraneics
 MEDICAL MANAGEMENT

DIPHTHERIA ANTITOXIN

1. Antitoxin will not neutralize toxin that is already fixed to tissues, but will neutralize circulating
(unbound) toxin and will prevent progression of disease.
2. The decision to administer diphtheria antitoxin must be based on the clinical diagnosis of
diphtheria without definitive laboratory confirmation, since each day of delay in treatment is associated with
increased mortality.
3. Because diphtheria antitoxin is produced in horses, it is necessary to inquire about possible allergy
to horse serum and to perform a conjunctival or intracutaneous test with diluted antitoxin for immediate
hypersensitivity
4. The dose of diphtheria antitoxin is based on the site of the primary infection and the duration and
severity of disease:
20,000 to 40,000 units for disease that has been present for 48 h and involves the pharynx or
larynx;
40,000 to 60,000 units for nasopharyngeal infections;
80,000 to 100,000 units for disease that is extensive, has been present for 3 days, or is
accompanied by diffuse swelling of the neck.
 ANTIBIOTICS

Erythromycin orally or by injection (40 mg/kg/day; maximum, 2 gm/day) for 14 days.

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 14 days.
Patients with cutaneous diphtheria and carriers can be treated orally with erythromycin (500 mg
four times daily) or rifampin (10mg/kg/day once daily) for 7 days.

SYMPTOMATIC THERAPY

Respiratory and cardiac function must be monitored closely.

Early intubation or tracheostomy is recommended when the larynx is involved or signs of
impending airway obstruction are detected.
Tracheobronchial membrane can sometimes be removed mechanically via the endotracheal tube
or tracheostomy.
Primary or secondary pneumonia should be diagnosed and treated promptly.
Sedative or hypnotic drugs that may mask respiratory symptoms are contraindicated.
Close electrocardiographic monitoring, treatment of arrhythmias, and electrical pacing for heart
block are essential.
Glucocorticoids do not reduce the risk of diphtheritic myocarditis or polyneuritis.
Ulcerative or ecthymatous cutaneous lesions should be treated with Burow's solution applied on
wet compresses after debridement of necrotic areas, and treatment for associated conditions such
as pediculosis, scabies, or underlying dermatoses should be instituted.

PROPHYLACTIC

For close contacts, especially household contacts, a diphtheria booster, appropriate for age, should be
given.
Contacts should also receive antibiotics benzathine penicillin G (600,000 units for persons less
than 6 years old and l,200,000 units for those 6 years old. receive antibiotics benzathine penicillin G
(600,000 units for per-sons less than 6 years old and l,200,000 units for those 6 years old and older) or a 7- to
10-day course of oral erythromycin, (40 mg/kg/day for children and 1 g/day for adults).
Identified carriers in the community should also receive antibiotics. Maintain close surveillance and
begin antitoxin at the first signs of illness.
 INFECTIOUS MONONUCLEOSIS

Epstein-Barr virus (EBV) is the cause of infectious mononucleosis (IM). The virus, a member of the
family Herpesviridae, consists of DNA.

PATHOGENESIS

EBV is transmitted by salivary secretions. The virus infects the epithelium of the oropharynx and
the salivary glands and is shed from these cells.
The virus spreads through the bloodstream and infects B cells expressing complement receptor type
2.
Polyclonal activation of B cells leads to the production of antibodies to host-cell and viral proteins.
During the acute phase of IM, up to 1% of circulating B cells in the peripheral blood is infect by
EBV. When B cells are infected by EBV in vitro, they become transformed and can proliferate
indefinitely.
The entire lymphoreticular system is involved in infection. Lymph nodes throughout the body are
effected with moderate enlargement and increased numbers of active lymphoid follicles.
Hepatocytes may demonstrate swelling associated with lymphocytic and monocytic portal
infiltration.
The spleen is enlarged with hyperplasia of the red pulp.

SIGNS AND SYMPTOMS OF INFECTIOUS MONONUCLEOSIS

Median Percentage of
Manifestation
Patients (Range)
Sore throat 75
Malaise 47
Headache 38
Abdominal pain, nausea, or vomiting 17
Chills 10
Lymphadenopathy 95
Fever 93
Pharyngitis or tonsillitis 82
Splenomegaly 51
Hepatomegaly 11
Rash 10
Periorbital edema 13
Palatal enanthem 7
Jaundice 5
 LABORATORY FINDINGS

The white blood cell count is usually elevated and peaks at 10,000 to 20,000/uL during the second
or third week of illness.
Lymphocytosis is usually demonstrable, with more than 10% atypical lymphocytes.
The atypical lymphocytes are enlarged lymphocytes that have abundant cytoplasm, vacuoles,
and indentations of the cell membrane.
Low-grade neutropenia and thrombocytopenia are common during the first month of illness.

COMPLICATIONS

1. Central nervous system (CNS) complications (usually do so during the first 2 weeks of EBV
infection)
neurologic abnormalities and headache
meningismus
meningitis and encephalitis
cerebellar ataxia
acute hemiplegia
cranial nerve palsies (especially ones involving cranial nerve VII)
Guillain-Barre syndrome
acute transverse myelitis, and peripheral neuritis.
The cerebrospinal fluid (CSF) contains mainly lymphocytes, with occasional atypical lymphocytes.

2. Splenic rupture
3. Upper airway obstruction
4. Bacterial superinfection.
5. Autoimmune hemolytic anemia