Diphtgeria in children

1. Presented by: Takreem Ilyas, PG 1st Year,
Department of Paediatrics,MIMS

3.  Introduction
 Etiology
 Epidemiology
 Pathogenesis and immunology
 Clinical manifestations
 Respiratory Diphtheria
 Cutaneous Diphtheria
 Infections Due to Non-diphtheriae Corynebacterium Species and Nontoxigenic C.
diphtheriae
 Other Clinical Manifestations
 Complications
 Diagnosis
 Treatment
 Antitoxin
 Antimicrobial Therapy
 Supportive Care
 Management Strategies
 Prognosis
 Prevention
 Prophylaxis Administration to Contacts

4.  nasopharyngeal and skin infection caused by Corynebacterium
diphtheriae.
 Four C. diphtheriae biotypes - mitis, intermedius, belfanti, gravis;
differentiated by colonial morphology, hemolysis, and fermentation
reactions
 Toxigenic strains of C. diphtheriae - protein toxin - systemic toxicity,
myocarditis, polyneuropathy.
 The toxin - formation of pseudomembranes in the pharynx in respiratory
diphtheria.
 toxigenic strains - pharyngeal diphtheria, nontoxigenic strains -
cutaneous disease.

5.  gram-positive bacillus - unencapsulated, nonmotile, and nonsporulating. aerobic,
pleomorphic,
 first identified microscopically in 1883 by Klebs and a year later was isolated in pure
culture by Loffler in Robert Koch’s laboratory.
 club-shaped bacillary appearance - typically clusters of parallel rays- palisades,
“Chinese characters.”
 Selective media - tellurite, colistin, or nalidixic acid
 may be isolated from individuals with both nontoxigenic (tox--) and toxigenic (tox++)
phenotypes.
 Uchida and Pappenheimer - corynebacteriophage beta carries the structural gene
“tox”, which encodes diphtheria toxin
 family of closely related corynebacteriophages responsible for lysogenic conversion
of tox-– C.diphtheriae to tox++ phenotype.
 Growth of toxigenic strains of C. diphtheriae under iron-limiting conditions ->
optimal expression of diphtheria toxin (pathogenic mechanism during human
infection).
 Other- Corynebacterium ulcerans and Corynebacterium pseudotuberculosis,

6.  exclusive inhabitant of human mucous membranes and skin.
 Transmission:
 primarily by airborne respiratory droplets,
 direct contact with respiratory secretions of symptomatic individuals,
 exudate from infected skin lesions.
 through contaminated milk and through an infected food handler (suspected)
 Asymptomatic respiratory tract carriage.
 Endemic areas- 3–5% of healthy individuals can carry toxigenic
organisms
 Diphtheria is endemic in INDIA.
 Skin infection and skin carriage- silent reservoirs
 organisms can remain viable in dust or on fomites for up to 6 mo.

7.  Cutaneous diphtheria - secondary infection - follows a
primary skin lesion due to trauma, allergy, or
autoimmunity.
 lack tox gene , do not express diphtheria toxin.
 tropical latitudes - cutaneous diphtheria more common
than respiratory diphtheria.
 Nontoxigenic strains - pharyngitis in Europe, outbreaks
in MSM illicit IV drugs users.

8.  Children aged 1-5yrs are commonly infected
 A herd immunity of 70% is required to prevent
epidemics
 Contaminated objects like thermometers, cups,
spoons, toys and pencils can spread the disease
 Overcrowding, poor sanitation and hygiene, illiteracy,
urban migration and close contacts can lead to
outbreak

9.  Diphtheria toxin (tox+ strains) - primary virulence factor
 synthesized in precursor form; released as a 535-
amino-acid, single-chain protein; and, 50% lethal dose
of ~100 ng/kg of body weight.
 toxin produced in the pseudomembranous lesion ->
taken up in the bloodstream, -> distributed to all organ
systems in the body.
 Binds cell surface receptor (a heparin-binding epidermal
growth factor–like precursor), -> receptor-mediated
endocytosis -> enters cytosol
 -> separatedinto two chains by digestion with serine
proteases: the N-terminal A fragment and the C-terminal
B fragment.
 A fragment in the eukaryotic cell cytosol results in ->
irreversible inhibition of protein synthesis by NAD+-
dependent ADP-ribosylation of elongation factor 2.
 -> death of the cell.

10.  Characteristic pathologic findings - mucosal ulcers with
pseudomembranous coating - inner band of fibrin , luminal band of
neutrophils. white and firmly adherent
 advanced diphtheria - pseudomembranes gray or green or black -
necrosis
 Mucosal ulcers - toxin-induced necrosis of epithelium with edema,
hyperemia, and vascular congestion of the submucosal base.
 significant fibrinosuppurative exudate from ulcer develops into the
pseudomembrane.
 severe respiratory diphtheria may extend from the pharynx into medium-
sized bronchial airways.
 Expanding and sloughing membranes -fatal airway obstruction.

11.  Respiratory Diphtheria
 Cutaneous Diphtheria
 Infections Due to Non-diphtheriae Corynebacterium Species and
Nontoxigenic C. diphtheriae
 Other Clinical Manifestations

12.  primary focus : tonsils or pharynx
 nose and larynx - next 2 most common sites.
 incubation period of 2-4 days (range 1-10 days)
 Nasal Diptheria - Infection of the anterior nares is more
common among infants -> serosanguineous, purulent,
erosive rhinitis with membrane formation.
 Shallow ulceration of the external nares and upper lip is
characteristic.
 Unilateral nasal discharge is quite pathognomic of nasal
diphtheria

13.  tonsillar and pharyngeal
diphtheria , sore throat is the
universal early symptom.
 Only half of patients have fever,
and fewer have dysphagia,
hoarseness, malaise, or
headache.
 Mild pharyngeal injection ->
unilateral or bilateral tonsillar
membrane formation, -> extend
to involve the uvula soft palate,
posterior oropharynx,
hypopharynx, or glottic areas ->
toxin-mediated paralysis,
 Underlying soft tissue edema of
the submandibular and
paratracheal region & enlarged
lymph nodes -> bull-neck
appearance. characterized by
foul breath, thick speech, and

14.  laryngeal diphtheria: Hoarseness, At significant risk for suffocation
because of local soft tissue edema and airway obstruction by the
diphtheritic membrane laryngoscopy may be diagnostically helpful.
 systemic manifestations effects of diphtheria toxin and include
weakness as a result of neurotoxicity and cardiac arrhythmias or
congestive heart failure due to myocarditis.
 Unlike the exudative lesion associated with streptococcal pharyngitis, the
pseudomembrane in diphtheria is tightly adherent to the underlying
tissues.
 Attempts to dislodge the membrane -> bleeding.

15.  punched-out ulcerative lesions with necrotic sloughing or pseudomembrane
formation.
 most commonly occur on the lower and upper extremities, head, and trunk.
 indolent, nonprogressive infection
 characterized by a superficial, ecthyma-like, nonhealing ulcer with a gray-
brown membrane.
 Diphtheria skin infections cannot always be differentiated from streptococcal
or staphylococcal impetigo, and these conditions frequently coexist.
 In most cases, a primary process, such as dermatosis, laceration, burn, bite,
or impetigo, becomes secondarily infected with C. diphtheriae.
 Local hyperesthesia or hypesthesia is unusual.
 Respiratory tract colonization or symptomatic infection with toxic
complications occurs in the minority of patients with cutaneous diphtheria.

17.  Non-diphtheriae species of Corynebacterium and related genera as well
as nontoxigenic strains of C. diphtheriae itself have been found in
bloodstream and respiratory infections, often in individuals with
immunosuppression or chronic respiratory disease.
 These organisms can cause disease manifestations and should not
necessarily be dismissed as colonizers

18.  Rare: endocarditis, septic arthritis, most often in patients with preexisting
risk factors (abnormal cardiac valves, injection drug use, cirrhosis.)
 ear (otitis externa),
 eye (purulent and ulcerative conjunctivitis),
 genital tract (purulent and ulcerative vulvovaginitis).
 The clinical setting, ulceration, membrane formation, and submucosal
bleeding help differentiate diphtheria from other bacterial and viral
causes.
 Rarely septicemia - universally fatal.
 skin was the probable portal of entry, and almost all strains were
nontoxigenic.
 Diphtheroids isolated from sterile body sites should not be routinely
dismissed as contaminants without careful consideration of the clinical
setting.

19.  Airway obstruction by pseudomembranes: bronchoscopy or intubation and
mechanical ventilation
 Children are particularly prone to obstruction because of their small
airways.
 late toxic manifestations: Polyneuropathy and myocarditis
 Myocarditis - arrhythmias and dilated cardiomyopathy.
 Toxic Cardiomyopathy:
-in 10-25% of patients
-responsible for 50-60% of deaths
 Tachycardia out of proportion to fever
-prolonged PR interval and changes in the ST-T wave
-Elevation of the serum aspartate aminotransferase concentration closely
parallels the severity of myonecrosis

20.  Polyneuropathy 3–5 weeks - severe and prolonged neurologic
abnormalities. typically reversible in patients who survive the acute
phase. Recovery from the neuritis is often slow but usually complete.
Corticosteroids are not recommended.
 mouth and neck- lingual or facial numbness, dysphonia, dysphagia,
a nasal quality in the voice, difficulty in swallowing and risk for
aspiration
 Cranial neuropathies (5th wk): oculomotor and ciliary paralysis-
strabismus, blurred vision, or difficulty with accommodation
 Symmetric polyneuropathy (10 days to 3 mo): motor deficits with
diminished deep tendon reflexes
 Monitoring for paralysis of the diaphragm muscle
 weakness of respiratory and abdominal muscles
 Sensory manifestations and sensory ataxia
 Autonomic dysfunction -> hypotension.
 Other complications : pneumonia, renal failure, encephalitis, cerebral
infarction, pulmonary embolism, and serum sickness from antitoxin
therapy.

21.  The diagnosis of diphtheria is based on clinical signs and symptoms plus
laboratory confirmation.
 The clinical diagnosis - sore throat; adherent tonsillar, pharyngeal, or
nasal pseudomembranous lesions; low-grade fever.
 diagnosis requires isolation of C. diphtheriae or histopathologic isolation
of compatible gram-positive organisms.
 confirmed respiratory diphtheria - laboratory proven or
epidemiologically linked to a culture-confirmed case
 probable respiratory diphtheria clinically but not laboratory proven or
epidemiologically linked
 Carriers positive culture for C. diphtheriae and who either are
asymptomatic or have symptoms but lack pseudomembranes.

22.  Laboratory diagnosis:
 Culture: from the nose and throat and any other mucocutaneous lesion. A
portion of membrane should be removed and submitted for culture along with
underlying exudate
 special selective medium and subsequent biochemical testing to
differentiate C. diphtheriae from other nasopharyngeal commensal
corynebacteria.
 laboratory notified to use selective medium.
 C. diphtheriae survives drying.
 If obtained in a remote area, a dry swab specimen can be placed in a
silica gel pack and sent to the laboratory.
 Culture isolates of coryneform organisms should be identified to the
species level, and toxigenicity and antimicrobial susceptibility tests
should be performed for C. diphtheriae isolates.

23.  demonstration of local lesions with characteristic histopathology.
 Corynebacterium pseudodiphtheriticum, a nontoxigenic organism,
is a common component of the normal throat flora and does not
pose a significant risk.
 Evaluation of a direct smear using Gram stain or specific
fluorescent antibody is unreliable.
 Elek test: rapid diagnosis (16-24 hrs)
 Enzyme immunossay
 PCR for A or B portion of the toxic gene “tox”
 Hypoglycemia, glycosuria, BUN, or abnormal ECG for liver, kidney and
heart involvement

24.  A diagnosis of cutaneous diphtheria requires laboratory confirmation
since the lesions are not characteristic and are indistinguishable from
other dermatoses. Diphtheritic ulcers occasionally—but not
consistently—have a punched-out appearance.
 Patients in whom cutaneous diphtheria is identified should have the
nasopharynx cultured for C. diphtheriae.
 The laboratory medium for cutaneous diphtheria specimens is the same
as that used for respiratory diphtheria: Loffler’s or Tinsdale’s selective
medium in addition to nonselective medium such as blood agar.

25.  DIPHTHERIA ANTITOXIN
 Mainstay of therapy
 Neutralizes only free toxin, efficacy diminishes with elapsed time
 Antitoxin is administered as a single empirical dose of 20,000-120,000 U
based on the degree of toxicity, site and size of the membrane, and
duration of illness
 The current protocol - a test dose. If hypersensitivity + require
desensitization before full therapeutic dose of antitoxin is administered.

26. ANTIMICROBIAL THERAPY
 Halt toxin production, treat localized infection and prevent transmission of
the organism to contacts
 erythromycin (40-50 mg/kg/day BD or QID [PO] or [IV]),
 aqueous crystalline penicillin G (100,000-150,000 U/kg/day 6 hrly IV or
[IM]), or
 procaine penicillin (12,500-25,000 U/kg/day 12 hrly IM) for 14 days
 penicillin was associated with a more rapid resolution of fever and a
lower rate of bacterial resistance than erythromycin; however, relapses
were more common in the penicillin group.
 Erythromycin therapy targets protein synthesis and thus offers the
presumed benefit of stopping toxin synthesis more quickly than a cell
wall–active β-lactam agent.
 Alternative therapeutic agents for patients who are allergic to penicillin or
cannot take erythromycin include rifampin and clindamycin.
 Other reasonable antibiotics are clarithromycin, azithromycin, linezolid,
and vancomycin, although they have not been studied in comparison to
the agents above.

27.  Elimination of the organism should be documented by negative results of
at least 2 successive cultures of specimens from the nose and throat (or
skin) obtained 24 hr apart after completion of therapy.
 For patients in whom the organism is not eradicated after a 14-day
course of erythromycin or penicillin, an additional 10-day course followed
by repeat culture is recommended.
 Drug-resistant strains of C. diphtheriae exist, and several reports have
described multidrug-resistant strains, predominantly in Southeast Asia.
Drug resistance should be considered when efforts at pathogen
eradication fail.
 Patients who recover from respiratory or cutaneous diphtheria should
have antitoxin levels measured. If diphtheria antitoxin has been
administered, this test should be performed 6 months later.
 Patients who recover from respiratory or cutaneous diphtheria should
receive the appropriate vaccine to ensure the development of protective
antibody titers.

28. SUPPORTIVE CARE
 Droplet precautions
 contact precautions
 until results of cultures of specimens taken after cessation of therapy are
negative.
 Cutaneous wounds are cleaned thoroughly with soap and water.
 Bed rest is essential during the acute phase of disease, usually for ≥2 wk
until the risk for symptomatic cardiac damage has passed, with return to
physical activity guided by the degree of toxicity and cardiac involvement.

29. MANAGEMENT
STRATEGIES
 hospitalized in respiratory isolation rooms, with close monitoring of
cardiac and respiratory function.
 cardiac workup
 extensive pseudomembranes, an anesthesiology or an ear, nose, and
throat consultation is recommended because of the possible need for
tracheostomy or intubation.
 In some settings, pseudomembranes can be removed surgically.
 Treatment with glucocorticoids has not been shown to reduce the risk of
myocarditis or polyneuropathy

30.  mortality rate -5–10%
 20% among children <5 years old and adults >40 years of age.
 Fatal pseudomembranous diphtheria - nonprotective antibody titers and in
unimmunized patients.
 Risk factors for death-
 bullneck diphtheria;
 myocarditis with ventricular tachycardia;
 atrial fibrillation;
 complete heart block;
 an age of >60 years or <6 months;
 alcoholism;
 extensive pseudomembrane elongation; and laryngeal, tracheal, or bronchial
involvement.
 important predictor of fatal outcome -interval between onset of local
disease and the administration of antitoxin.
 Cutaneous diphtheria -low mortality rate ,rarely associated with myocarditis
or peripheral neuropathy.

31.  Vaccination
 Currently, diphtheria toxoid vaccine is coadministered with tetanus
vaccine (with or without acellular pertussis).
 DTaP (full-level diphtheria toxoid tetanus toxoid, and acellular pertussis
vaccine) is currently recommended for children up to the age of 6;
 DTaP replaced the earlier whole-cell pertussis vaccine DTP in developed
countries.
 Tdap is a tetanus toxoid, reduced diphtheria toxoid, and acellular
pertussis vaccine formulated for adolescents and adults.
 recommended for children ≥7 years old and for adults. It is
recommended that all adults (i.e., persons >19 years old) receive a
single dose of Tdap if they have not received it previously, regardless of
the interval since the last dose of Td (tetanus and reduced dose
diphtheria toxoids, adsorbed).
 priority for health care workers, pregnant women, adults anticipating
contact with infants, and adults not previously vaccinated for pertussis.
 Adults who have received acellular pertussis vaccine should continue to
receive decennial Td booster vaccinations.

32.  Close contacts of diphtheria patients should undergo throat culture to
determine whether they are carriers.
 antimicrobial prophylaxis should be considered for all contacts, even those
whose cultures are negative.
 7–10 days erythromycin (40-50 mg/kg/day divided qid PO for 10 days
 Or single injection of benzathine penicillin G (600,000U IM for patients
<30 kg, 1,200,000U IM for patients ≥30 kg)
 (1.2 million units for persons ≥6 years of age or 600,000 units for children <6
years of age).
 Diphtheria toxoid vaccine Tdap-to immunized individuals who have not
received a booster dose within 5 yr. Children who have not received their 4th
dose should be vaccinated. Those who have received fewer than 3 doses of
diphtheria toxoid or who have uncertain immunization status are immunized
with an age-appropriate preparation on a primary schedule
 Carriers - treated and vaccinated when identified.

34.  Introduction
 Microbiology
 Epidemiology
 Pathogenesis
 Immunity
 Clinical Manifestations
 Complications
 Diagnosis
 Differential Diagnosis
 Treatment
 Prevention
 Immunization

35.  Pertussis is highly contagious acute bacterial infection of the respiratory
tract caused by Bordetella pertussis.
 pertussis means “violent cough” most consistent and prominent feature
of the illness.
 The inspiratory sound made at the end of an episode of paroxysmal
coughing gives rise to the common name for the illness, “whooping
cough.”
 variable: it is uncommon among infants ≤6 months of age frequently
absent in older children and adults.
 Chinese name “the 100-day cough,”
 The identification of B. pertussis was first reported by Bordet and
Gengou in 1906, and vaccines were produced over the following two
decades

36.  Currently worldwide prevalence is diminished due to active
immunization
 However it remains a public health problem among older children
and adults
 It continues to be an important respiratory disease afflicting
unvaccinated infants and previously vaccinated children and
adults (waning immunity)

37.  10 identified species, only four - major medical significance.
 B. pertussis infects only humans and is the most important Bordetella
species causing human disease.
 B. parapertussis causes an illness in humans that is similar to pertussis
but is typically milder; co-infections with B. parapertussis and B. pertussis
 Both respiratory infection and opportunistic infection due to B.
bronchiseptica are reported occasionally in humans.
 B. petrii, B. hinzii, and B. ansorpii have been isolated from patients who
are immunocompromised.

38.  Bordetella species are gram-negative pleomorphic aerobic bacilli
 slow-growing fastidious organism that requires selective medium
 forms small, glistening, bifurcated colonies.
 Suspicious colonies are presumptively identified as B. pertussis by direct
fluorescent antibody testing or by agglutination with species-specific
antiserum.
 B. pertussis is further differentiated from other Bordetella species by
biochemical and motility characteristics.

39.  under the control of a single genetic locus
 most important virulence factor pertussis toxin, B oligomer–binding subunit and an
enzymatically active A protomer that ADP-ribosylates a guanine nucleotide–binding
regulatory protein (G protein) in target cells, producing a variety of biologic effects.
 Pertussis toxin - mitogenic activity,
 affects the circulation of lymphocytes,
 serves as an adhesin for bacterial binding to respiratory ciliated cells.
 filamentous hemagglutinin, a component of the cell wall,
 pertactin, an outer-membrane protein.
 Fimbriae, bacterial appendages that play a role in bacterial attachment,
 These agglutinating antibodies primary means of serotyping B. pertussis strains.
 tracheal cytotoxin, a peptidoglycan fragment, which causes inflammatory respiratory
epithelial damage;
 adenylate cyclase-hemolysin toxin, impairs host phagocytic cell function;
 dermonecrotic toxin, may contribute to respiratory mucosal damage;
 lipooligosaccharide, properties similar to those of other gram-negative bacterial
endotoxins.

40. EPIDEMIOLOGY
 attack rates 80–100% among unimmunized household contacts 20%
within households in well-immunized populations.
 Worldwide distribution,
 cyclical outbreaks every 3–5 occurs in all months; peaks in winter.
 In developing countriesimportant cause of infant morbidity and death.
 The WHO estimates -161,000 deaths among children <5 years of age in
2014.
 In unimmunized populations, incidence peaks preschool years, half of
children have the disease before reaching adulthood.
 In highly immunized populations peak incidence is among infants <1 year
of age
 Severe morbidity and high mortality rates -infants.

41.  Transmission: through the respiratory route in the form of droplet
infection
 Adolescents and adults are the reservoir. No animal or insect reservoir

42.  attachment of the organism the ciliated epithelial cells of the
nasopharynx. Mediated by surface adhesins (e.g., pertactin and
filamentous hemagglutinin), ->bind to the integrin family of cell-surface
proteins in conjunction with pertussis toxin.
 At the site of attachment, the organism multiplies
 producing a variety of other toxins
 local mucosal damage (tracheal cytotoxin, dermonecrotic toxin).
 Impairment of host defense by B. pertussis mediated by pertussis toxin
and adenylate cyclase-hemolysin toxin.
 local cellular invasion, with intracellular bacterial persistence;
 systemic dissemination does not occur.
 Systemic manifestations (lymphocytosis) -effects of the toxins.

43.  neurologic events in pertussis, seizures and encephalopathy, due to
hypoxia from coughing paroxysms or apnea rather than to the effects of
specific bacterial products.
 B. pertussis pneumonia, which occurs in up to 10% of infants - diffuse
bilateral primary infection.
 Older children and adults, pneumonia secondary to bacterial infection
with streptococci or staphylococci.
 Deaths from pertussis young associated with very high levels of
leukocytosis and pulmonary hypertension.

44. -This exudate predisposes to atelectasis, cough, cyanosis and
pneumonia -Organism causes local tissue damage and systemic
effects mediated through its toxin
The organism get attached to the respiratory cilia and toxin causes
paralysis of cilia
muocopurulent-sanguineous exudate forms in the respiratory tract

45. CLINICAL
MANIFESTATIONS
 prolonged coughing illness. classic pertussis -preschool and school-age
children.
 Incubation period: 7-10 days
 Infection lasts for 6 weeks – 10 weeks
 Stage I (catarrhal stage; 1-2 weeks): insidious onset of coryza,
sneezing, low grade fever and occasional cough
 Stage II (paroxysmal cough stage; 1-6 weeks): cough more frequent
and spasmodic due to difficulty in expelling the thick mucous form the
tracheobronchial tree. ith repetitive bursts of 5–10 coughs, often within a
single expiration.
 Post-tussive vomiting mucous plug expelled at the end of an episode.
 episode may be terminated by an audible whoop,
 neck-vein distension, bulging eyes, tongue protrusion, and cyanosis.
seizures
 Paroxysms may be precipitated by noise, eating, or physical contact.

46.  The frequency of paroxysmal episodes varies widely, from several per hour
to 5–10 per day.
 Episodes are often worse at night interfere with sleep.
 Most complications occur during the paroxysmal stage. Fever is uncommon
and suggests bacterial superinfection.
 Cough increase for next 2-3 weeks and decreases over next 10 weeks
 Absence of whoop and/or post-tussive vomiting does not rule out clinical
diagnosis of pertussis
paroxysmal cough>2 weeks with or without whoop and/or post-tussive
vomiting is the hallmark feature of pertussis
 Stage III (convalecence stage): period of gradual recovery even up to 6
months
 For 6–12 months, intercurrent viral infections may be associated with a
recrudescence of paroxysmal cough.

48.  More common among infants than among older children or adults.
 Subconjunctival hemorrhages, abdominal and inguinal hernias,
pneumothoraces, and facial and truncal petechiae
 Weight loss Urinary incontinence, rib fracture, carotid artery aneurysm,
and cough syncope in adolescents and adults with pertussis
 Secondary pneumonia (1 in 5) and apneic spells (50%; neonates and
infant<6 months of age)
 Neurological complications: seizures (1 in 100) and encephalopathy (1 in
300) due to the toxin or hypoxia or cerebral hemorrhage
 Otitis media, anorexia and dehydration, rib frcture, pneumothorax,
subdural hematoma, hernia and rectal prolapse

49. 1. Suspected on the basis of history and clinical examination and is confirmed by
culture, genomics or serology
2. Elevated WBC count with lymphocytosis. The absolute lymphocyte count of
≥20,000 is highly suggestive
3. Culture of nasopharyngeal secretions remains the gold standard of
diagnosis because of its 100% specificity,
4. The best specimen nasopharyngeal aspiration, fine flexible plastic
catheter attached to a 10-mL syringe is passed into the nasopharynx and
withdrawn while gentle suction is applied. secretions for culture should be
inoculated without delay onto appropriate medium (Bordet-Gengou or
Regan-Lowe), or the catheter should be flushed with a phosphate-
buffered saline solution for culture and/or PCR.
5. An alternative to the aspirate is a Dacron or rayon nasopharyngeal swab;
appropriate transport medium (e.g., Regan-Lowe charcoal medium)
should be used.
6. cultures become positive by day 5 of incubation.
7. Nasopharyngeal cultures in untreated pertussis remain positive for a
mean of 3 weeks after the onset of illness; these cultures become
negative within 5 days of the institution of appropriate antimicrobial
therapy.

50.  PCR: most sensitive to diagnose; can be done even after antibiotic
exposure. It should always be used in addition with cultures
 Results of PCR can be available within hours;
 Enzyme immunoassays detecting IgA and IgG antibodies to pertussis
toxin, filamentous hemagglutinin, pertactin, and fimbriae have been
developed and assessed for reproducibility. Two- or fourfold increases in
antibody titer are suggestive of pertussis, although cross-reactivity

51.  A child presenting with paroxysmal cough, post-tussive vomiting, and
whoop or any respiratory symptoms after contact with a laboratory-
confirmed case of pertussis.
 is likely to have an infection caused by B. pertussis or B. parapertussis;
lymphocytosis increases the likelihood of a B. pertussis etiology.
 Viruses respiratory syncytial virus, rhinovirus, and adenovirus represent
co-infection, particularly in children <1 year of age.
 Other etiologies - Mycoplasma pneumoniae, Chlamydia pneumoniae,
adenovirus, influenza virus, and other respiratory viruses.
 Foreign body aspiration, endobronchial tuberculosis and a mass pressing
on the airway
 reactive airway disease, and gastroesophageal reflux disease -
noninfectious causes.

52.  ANTIBIOTICS
 effective only if started early in the course of illness.
 Erythromycin (40-50 mg/kg/day 6 hrly orally for 2 weeks or Azithromycin 10
mg/kg for 5 days in children<6 months and for children>6 months 10 mg/kg on
day 1, followed by 5mg/kg from day2-5 or Clarithromycin 15 mg/kg 12 hrly
for 7 days
 SUPPORTIVE CARE
 hospitalized. A quiet environment
 decrease the stimulation that can trigger paroxysmal episodes.
 of β-adrenergic agonists and/or glucocorticoids
 Cough suppressants are not effective and play no role in the
management of pertussis.

53.  INFECTION CONTROL MEASURES
 Hospitalized patients with pertussis - respiratory isolation, precautions
appropriate for pathogens spread by large respiratory droplets.
 Isolation should continue for 5 days after initiation of macrolide therapy
or, in untreated patients, for 3 weeks (i.e., until nasopharyngeal cultures
are consistently negative).

54.  Chemoprophylaxis regardless of immunization status
 initiated within 21 days of cough onset in the index case.
 erythromycin estolate (50 mg/kg per day; maximum dose, 1 g/d)
 members at high risk of severe disease (children <1 year of age,
pregnant women).
 All household contacts should be given erythromycin for 2 weeks
 Children <7 years of age not completed the four primary dose
should complete the same at the earliest
 Children <7 years of age completed primary vaccination but not
received the booster in the last 3 years have to be given a single
booster dose
 VACCINE

55. IMMUNIZATION
 active immunization.
 Whole-cell pertussis vaccines are prepared through the heating,
chemical inactivation, and purification of whole B. pertussis organisms.
 adverse events—common (fever;injection-site pain, erythema, and
swelling; irritability)
 Uncommon (febrile seizures, hypotonic-hyporesponsive episodes).
 acellular pertussis vaccines, which are effective and less reactogenic
 .

56.  whole-cell vaccines are still used extensively in developing regions
 acellular pertussis vaccines developed world.
 WHO Strategic Advisory Group of Experts (SAGE) recommends that
countries using whole-cell pertussis vaccine for the primary infant
immunization series continue to do so.
 In countries using acellular pertussis vaccines in infancy, additional
booster immunizations in older children, adolescents, and adults are
recommended to prevent pertussis in high-risk infants.

57.  Pertussis immunization is also recommended during pregnancy to
increase passive transfer of maternal antibodies to the fetus
 immunization of women during pregnancy is 90–93% effective at
preventing pertussis in infants <2 months of age and is safe.
 DPT vaccine: 3 primary doses starting at 6 weeks of age
 1st booster at 16-18 months of age, 2nd booster at 5 years of age
 At 10 years of age Tdap/Td followed by Td every 10 years
 Catch-up vaccination:
 Below 7 years: DPT at 0,1 and 6 months

58.  Known as triple antigen
 2types DTwP and DTap
 DTwP – composed of tetanus(5-25 lf per dose) and diphtheria
toxoids(20 – 30 lf) and whole cell pertusis bacilli adsorbed on to
aluminium salts,which acts as adjuvants.
 Dose 0.5ml, i.m., stored at 2°-8°C
 Dosing : 3 primary doses at 6,10,14 wks and 2 boosters at 15-18
months & 5 yrs.

59.  DTaP vaccine: is acellular pertusis vaccine, has the advantage of
lesser side effects, when compared with DTwP and
other important advantage of the aP vaccines is the reproducible
production process with its use of purified antigens and the removal of
LPS and other parts of the bacterial cell wall during the purification of
soluble antigenic material.

60.  Adverse effects following DTwP vaccines:
Minor- pain, swelling, redness, fever,vomitings
Others - are persistant inconsolable crying, seizures (within 72hrs
of DTwP), encephalopathy and HHE(hypotonic
hyporesponsiveness)

61.  C/I: absolute are
1) with h/o of anaphylaxis
2)development of encephalopathy within 7days of DTwP
vaccine
Relative c/I are
1) persistant inconsolable cry>3hrs
2)HHE with in 48 hrs of DT wP
3)seizures with n 72 hrs of DTwP

62. Catch-up schedule: The 2nd childhood booster is not required if the
last dose has been given beyond the age of 4 years
Catch up below 7 years: DTwP/DTaP at 0, 1 and 6 months
Catch up above 7 years: Tdap, Td, and Td at 0, 1 and 6 months

63.  standard quantity tetanus toxoid and reduced quantity diphtheria
and acellular pertussis vaccine (Tdap).
 Recommended schedule: One dose of Tdap to all adolescents
aged 11 through 12 years.