It’s the simple things in life we forget
You hear her talkin’ but don’t hear what she said
Why do you make something so easy so complicated?
Searching for what’s right in front of your face..
- Simple Things by Usher
Jerry V. Pua MD
2 nd year Resident


To discuss etiology, differential diagnosis and work up for children presenting with cough

To discuss approach, diagnosis, management, recommendations and prevention of B. pertussis infection





A.E.
6 month old, Female
Filipino, Catholic
Brgy. Batasan Hills, Quezon City

Consulted at ER last June 15, 2013


Informant: Grandmother
Reliability: 80%

Chief Complaint

• Non productive cough
• No fever nor other associated symptoms
• No consult done
• Persistence of recurring bouts of cough
• No other associated symptoms
• Consulted LHC – Carbocisteine and
Amoxicillin (40mkday)

• Persistence of continous non productive cough followed by facial cyanosis
• Difficulty breathing – alar flaring, tachypnea, ‘seesaw’ breathing
• Persistence of symptoms prompted consult at Local Clinic
• A> Bronchopneumonia rule out Pertussis
• Advised consult at a tertiary institution


Decrease appetite

No failure to thrive, feeding interruption

No skin lesions

No diaphoresis, no fainting spells

No vomiting, no diarrhea nor constipation

No pallor

No facial redness during bouts of cough

No convulsion

No limitation of movements

No bleeding manifestations

(+) cough (+)
(+)
No heredo-familial disease on both sides of the family




Born to 39 year old G5P4 (4014) non smoker, non alcoholic beverage drinker mother
No pre natal check up, denies maternal illness
Multivitamins, Ferrous Sulfate intake


Delivered Full term via NSD at home assisted by traditional birth attendant
No feto-maternal complication during and after the delivery


No immunization received


Milk Formula – since birth

No milk formula intolerance

Complimentary feeding – 6 months old

No interrupted feeding

No feeding problems


Motor

Head control – 2 mos. rolls over – 4 mos. sits with support –
6 mos.

Language

Imitates sounds – 5mos

Daily Living

Put anything at the mouth – 4 mos.

Social/Adaptive

Social smile – 2 mos. plays with caregiver – 6 mos





No routine check up
No previous hospitalization
No previous surgical intervention done.
No allergies






Awake, irritable, in mild respiratory distress. Well hydrated.
Weight: 6 kg (z score below 0 )
Height: 65 cm (z score 0 )
BP 80/50 HR 122
RR 38 T 37.1

Skin: Warm, Moist, No rashes or other dermatosis.
No cyanosis.





HEENT: Normocephalic. Aniceteric sclera; pink palpebral conjunctivae; no eye discharge
(+) intermittent alar flaring. No nasal discharge nor bleeding. No tragal tenderness, no aural discharge
Non hyperemic posterior pharyngeal wall, no exudates, uvula midline
(+) cervical lympadenopathy, bilateral

Chest and Lungs: No chest deformity nor skin lesions at the chest. Symmetrical chest expansion, (+) subcostal and intercostals retractions (+) crackles on both lung fields


Heart: Adynamic precordium, Apex beat at 4 th ICS
LMCL, normal rate regular rhythm, no murmur

Abdomen: Globular, No visible veins. Normoactive bowel sounds. Soft, non tender, no organomegaly.


Genitalia: Grossly female
Extremities: No preferential movement. Pulses on all extremities are full and equal. No clubbing,
cyanosis of fingers or toes. CRT <2 seconds. No deformities.







Mental Status: Awake, irritable. GCS 15
Cranial Nerves: Intact
Motor: Good muscle tone, no fasciculation or atrophy, no involuntary movement. MMT 5/5 on all extremities. DTR’s 2++
Sensory: No deficit. No babinski or clonus.
Cerebellar: No nystagmus
Meningeal signs: No Kernig’s, No Brudzinski, No nuchal rigidity

Admitting Impression

SYMPTOMS, SIGN, OR LABORATORY
FINDINGS PATHOGNOMONIC OF A
DISEASE
Approach to Diagnosis


Most common symptom presenting to medical practitioners

Cough is a forced expulsive maneuver, usually against a closed glottis

Sound of a cough is due to vibration of larger airways and laryngeal structures during turbulent flow in expiration
Cough quality in children: a comparison of subjective vs. bronchoscopic findings
Anne Bernadette Chang, et. al
Dept of Paediatrics & Child Health, University of Queensland
Dept Respiratory Medicine, Royal Children's Hospital, Brisbane


Estimating the duration of cough is the first step in narrowing the list of possible diagnoses
THE DIAGNOSIS AND TREATMENT OF COUGH
RICHARDS. IRWIN, M.D.,AND J. MARK MADISON, M.D.
The New England Journal of Medicine





Acute Cough -- a recent onset of cough lasting <3 weeks
Subacute Cough (Prolonged acute cough) -- cough slowly resolving over a 3–8-week period
Chronic Cough -- A cough lasting >8 weeks
Recurrent Cough -- cough without a cold is taken as repeated (>2/year) cough episodes, apart from those associated with colds, that each last more than 7–14 days
Recommendations for the assessment and management of cough in children
M D Shields, A Bush, M L Everard, S McKenzie, R Primhak, on behalf of the
British Thoracic Society Cough Guideline Group


Cough lasting for a maximum of 3 weeks

Common caused: URTI, acute bronchitis or tracheobronchitis (bacterial or viral)

Such infections is usually self limited and subsides within one to two weeks along the clearing of the infection

No targets or reliable measures to predict the duration of cough at its onset, also to predict which will persist into sub acute or chronic cough
COUGH MANAGEMENT: A Practical Approach
F. De Blasio, et. al

COUGH MANAGEMENT: A Practical Approach
F. De Blasio, et. al

COUGH MANAGEMENT: A Practical Approach
F. De Blasio, et. al



Specific Cough -- one in which there is a clearly identifiable cause
Non specific isolated Cough -- typically have a persistent dry cough, no other respiratory symptoms, well with no signs of chronic lung disease and have a normal chest radiograph

Post viral Cough -- cough originally starting with an upper respiratory tract infection but lasting <3 weeks
Recommendations for the assessment and management of cough in children
M D Shields, A Bush, M L Everard, S McKenzie, R Primhak, on behalf of the
British Thoracic Society Cough Guideline Group


Classic Recognizable Cough

Certain cough characteristics classically taught to point to specific etiologies

Dry Cough

Wet Cough
Cough in children: definitions and clinical evaluation
Position statement of the Thoracic Society of Australia and New Zealand


6 months old

2 weeks history of cough

No fever

Cyanosis at bouts of cough

Difficulty of breathing

Siblings with cough

No immunization received

In mild respiratory distress

Intermittent alar flaring

Intercostal and subcostal retractions

Crackles on both lung fields

Patient: A.E.
6 months old, Female
Working Impression:
Bronchopneumonia
Rule out Pertussis

st
Arterial Blood Gas pH 7.24 pCO2 26 pO2 179 O2sat 99
HCO3 11.1 BE - 14.7
CBC w/ PC
Hgb 37.7 Hct
WBC 35.5 Seg
0.42
21
Lympho 79 Platelet 647


Cough lasting at least 2 wk with at least 1 of the following symptoms:
 paroxysms of coughing
 inspiratory whooping
 posttussive vomiting (ie, vomiting immediately after coughing)


Clinical case: a case that meets the clinical definition, but is not laboratoryconfirmed
Laboratory-confirmed case: a case that meets the clinical case definition and is laboratory-confirmed
Clinical Definitions of Pertussis: Summary of a Global Pertussis Initiative
Roundtable Meeting, February 2011




Cough illness lasting ≥ 2 weeks with 1 of the following without apparent cause:

Paroxysms of coughing

Inspiratory “whoop”

Posttussive vomiting
Probable case: symptoms, absence of laboratory confirmation and epidemiologic linkage to a laboratory-confirmed case of pertussis
Confirmed case: symptoms + > 1 following – PCR positive for pertussis or contact with laboratory-confirmed case of pertussis
Clinical Definitions of Pertussis: Summary of a Global Pertussis Initiative
Roundtable Meeting, February 2011


Common laboratory diagnostic methods:

Culture – gold standard

Direct antigen detection PCR

Direct fluorescent antibody (DFA) testing

Serologic demonstration enzyme-linked immunosorbent assay (ELISA) or Western blot with various B. pertussis antigens and agglutination
 Measuring an increase in titers between acute and convalescence phase serum specimens or high single serum antibody values
Defining Pertussis Epidemiology
Clinical, Microbiologic and Serologic Perspectives
James D. Cherry, MD, et al Pediatr Infect Dis J 2005



Proper performance of culture, PCR and ELISA to measure increases or decreases in IgG and IgA antibody titers to
Pertussis Toxin in paired serum samples, the sensitivity and specificity of the laboratory diagnosis of B. pertussis infection
The greatest sensitivity is obtained when culture, PCR and serologic testing are all performed on individuals with cough illness
Defining Pertussis Epidemiology
Clinical, Microbiologic and Serologic Perspectives
James D. Cherry, MD, et al Pediatr Infect Dis J 2005


Key factors for the successful application of PCR in the diagnosis of infection by Bordetella spp.:

Sample collection and processing

DNA purification

Primer selection

Amplification conditions

PCR as a diagnostic tool has the advantage of a much higher sensitivity compared with conventional culture
Defining Pertussis Epidemiology
Clinical, Microbiologic and Serologic Perspectives
James D. Cherry, MD, et al Pediatr Infect Dis J 2005


A 2.6-fold increase in detection of B. pertussis using PCR
compared with culture

PCR results were compared with serologic diagnosis;
PCR had a sensitivity of 61% and a specificity of 88%

Patients with symptoms meeting the CDC clinical case definition for pertussis and who had a specimen positive by PCR or DFA were considered to have true B. pertussis infections
Defining Pertussis Epidemiology
Clinical, Microbiologic and Serologic Perspectives
James D. Cherry, MD, et al Pediatr Infect Dis J 2005

nd
Diagnostic
Referred to Infection Control Committee
Blood CS
Nasopharyngeal Pertussis PCR
2D Echo with PAP

Hemoglobin
Hematocrit
WBC Count
Diff. Count
Segmenter
Lymphocytes
Monocytes
Platelet
06/15/13 06/16/13 06/17/13 06/18/13 06/20/13
137.7
125.1
126.2
131.4
140.3
0.42
35.5
0.38
27.5
0.38
25.9
0.40
19.2
0.43
16.8
21
79
647
14
72
10
523
16
65
15
537
21
62
14
539
31
63
06
465


A total count of ≥ 20,000 WBCs/mm3 with ≥
10,000 lymphocytes/mm3 in a young infant with coryza, cough, apnea or other respiratory distress is indicative of B. pertussis infection

A total count of ≥ 30,000 WBCs/mm3 is cause for concern and the rapidity of the WBC count rise is also an important indicator of worsening condition
Pertussis in Young Infants – Guidance for Clinicians
James D. Cherry MD, et. al. May 2010


Blood Culture and Sensitivity:

No growth for 5 days of incubation


POSITIVE for Bordetella pertussis DNA

Final Diagnosis


Acute respiratory infection caused by Bordetella pertussis

‘intense cough’

Extremely contagious -- attack rates as high as
100% in susceptible individuals exposed to aerosol droplets at close range


Tiny, fastidious, gram-negative coccobacilli that colonize only ciliated epithelium

Expresses pertussis toxin (PT), the major virulence protein

After aerosol acquisition, pertussis organism attaches to ciliated respiratory epithelial cells

Tracheal cytotoxin, adenylate cyclase, and PT appear to inhibit clearance of organisms

Responsible for the local epithelial damage


Worldwide, pertussis is a significant cause of infectious mortality

20 to 40 million cases

200,000 to 400,000 death per years

Most of cases and deaths occur in infancy
WHO. Pertussis vaccines. Wkly Epidemiol Rec. 1999;74:137 –143


Philippine Pediatric Society Registry

99 out of 1935660 cases

Philippine Children’s Medical Center

32 cases: Total probable and confirmed pertussis cases admitted from JANUARY-JUNE 2013


Rate of subclinical infection is as high as 80%

Coughing adolescents and adults -- major reservoir for B. pertussis -- usual sources of infection for infants and children

Household contact with infected adolescent and
adults – major source of pertussis infection in not fully immunized infants
Infant Pertussis and Household Transmission n Korea.
The Korean Academy of Medical Sciences.


Catarrhal stage (1-2 wk) begins insidiously after an incubation period (3-12 days)

Paroxysmal stage (2-6 wk) onset marks by coughing

Cough begins as a dry, intermittent, irritative hack and evolves into the inexorable paroxysms

Post-tussive emesis is common, and exhaustion is universal.

Convalescent stage (≥2 wk), the number, severity, and duration of cough episodes diminishes




Catarrhal stage -- characterized by excessive sneezing or
“throat clearing” -- adherence of organism in the ciliated epithelium throughout the respiratory tract – tissue necrosis, production of mucus, and inflammatory cell response
Paroxysmal stage – atypical

Acute life-threatening episode is common

Spells of cough leading to cyanosis or bradycardia and limpness as well as apnea

Post-tussive vomiting is common
“whoop cough” is rarely present in very young infant
Review: Age-Specific Presentation and Burden of Pertussis by Sarah Long M.D.

st -
nd
Management
Isolation
D5LR (mild)
O2 at 10Lpm
Medications:
Ampicillin (100)
Erythromycin (40) ---- Azithromycin (10)
Salbutamol nebulization every 4 hours
NPO


Assess progression of disease and likelihood of lifethreatening events at peak of disease

Prevent or treat complications

Educate parents in the natural history of the disease and in care that will be given at home


Limit the number of paroxysms

Observe the severity of the cough

Provide assistance when necessary

Maximize nutrition, rest, and recovery without sequelae

Age
Primary Agents
Azithromycin
<1 mo 10 mg/kg/day in a single dose for 5 days
Alternate Agents
Erythromycin
(Infantile hypertrophic pyloric stenosis)
40-50 mg/kg/day in 4 divided doses for 14 days
Clarithro
Not recommended
(safety data unavailable)
TMP-SMZ
Contraindicated for infants aged <2 mo (risk for kernicterus)
1-5 mo 10 mg/kg/day in a single dose for 5 days
40-50 mg/kg/day in 4 divided doses for 14 days
15 mg/kg/d in 2 divided doses for 7 days
Contraindicated at age
<2 mo
For infants aged ≥2 mo:
TMP 8mg/kg/day plus
SMZ 40 mg/kg/day in
2 divided doses for 14 days
Infants aged
≥6 mo and child
10 mg/kg in a single dose on day 1
(maximum 500 mg), then 5 mg/kg/day
(maximum 250 mg) on days 2-5
40-50 mg/kg/day
(maximum 2 g/day) in
4 divided doses for 14 days
15 mg/kg/d in 2 divided doses
(maximum
1 g/day) for
7 days
TMP 8 mg/kg/day plus
SMZ 40 mg/kg/day in
2 divided doses for 14 days


Life-threatening complications are most common in infants younger than 3 months

Respiratory tract complications: apnea, bacterial pneumonia, and pulmonary hypertension

Secondary bacterial pneumonia – leading identified cause of pertussis-related infection
Review: Age-Specific Presentation and Burden of Pertussis by Sarah Long M.D.


Respiratory Failure with Pertussis may stem from complications of Pneumonia, Pulmonary
Hypertension, and Apnea

Apnea – due to failure of self-rescue breathing at the end of a paroxysm of coughing or profound vagal stimulation

Infants intubated due to respiratory failure secondary to apnea have better prognosis than those intubated due to pneumonia or pulmonary hypertension
Review: Age-Specific Presentation and Burden of Pertussis by Sarah Long M.D.


Severe Bordetella pertussis consist of constellation of bronchopneumonia, extreme leukocytosis, refractory hypoxemia, and pulmonary hypertension

White blood cell counts >100 000 in the setting of
B. pertussis pneumonia associated with increase mortality
Pertussis Pneumonia, Hypoxemia, Hyperleukocytosis, and Pulmonary Hypertension:
Improvement in Oxygenation After a Double Volume Exchange Transfusion
Michael J. Romano, et. al. Pediatrics 2004

Infection of tracheal epithelium with
Bordetella pertussis
Ciliostasis, epithelial damage and compromised mucociliary clearance apnea
Pulmonary Infection
Necrotizing bronchopneumonia
Toxin mediated leukocytosis hypoxemia
ARDS
Increase whole blood mass
Pulmonary vasoconstriction Increase vascular resistance
PULMONARY HYPERTENSION
Cardiac Failure and Shock
Pathology and Pathogenesis of Fatal
Bordetella pertussis Infection in Infants
Christopher D. Paddock, et. al.

rd
th

The rest of hospital stay patient completed her antibiotics.

O2 supplementation was titrated down and eventually discontinued.

Patient discharged well and stable.







Infants less than or equal 3 months old with clinical deterioration
White Cell Count more than or equal to 30, 000 or rapidly rising in count (>10,000 in 6 hours)
Respiratory failure or frequent apnea
Progressive pneumonic changes in CXR
Persistent tachycardia/ cardiovascular instability
Neurological symptoms including seizure
South Thames Retrieval Service Guideline


Apnea, pneumonia, and seizures are the most common presenting symptoms requiring ICU care

Leukocytes aggregate within the pulmonary circulation and form a mechanical obstruction to transpulmonary blood flow with the result being severe hypoxemia and pulmonary hypertension

Cardiac failure associated with critical pertussis is likely right sided heart failure secondary to the pulmonary hypertension


Multiple authors have reported double volume exchange transfusion as an effective therapy for the pulmonary hypertension, and secondarily the hypoxemia and cardiac failure

Technique of double volume exchange utilized is the same as performed for the newborn with hyperbilirubinemia

Hypomagnesemia and especially hypocalcemia may occur thus recommended routine calcium supplementation
Chen H, Lee M, Tsao L. Exchange Transfusion Using Peripheral Vessels Is Safe and Effective in
Newborn Infants. Pediatrics 2008


White cell count more than or equal to 30,000 and rapidly rising count

White cell count more than or equal to 30, 000 with pneumonia or hemodynamic instability

White cell count more than or equal 50,000
South Thames Retrieval Service Guideline


Appearance of respiratory symptoms paralleled the rise in leukocyte count

Temporal relationship between the initiation of exchange transfusion and improvement in oxygenation
Pertussis Pneumonia, Hypoxemia, Hyperleukocytosis, and Pulmonary Hypertension:
Improvement in Oxygenation After a Double Volume Exchange Transfusion
Michael J. Romano, et. al. Pediatrics 2004

Pertussis Pneumonia, Hypoxemia, Hyperleukocytosis, and Pulmonary Hypertension:
Improvement in Oxygenation After a Double Volume Exchange Transfusion
Michael J. Romano, et. al. Pediatrics 2004


Over a 48-hr period disease severity is unchanged or diminished

No intervention is required during paroxysms

Nutrition is adequate

No complication has occurred

Parents are adequately prepared for care at home


Efficacy of the vaccine in reducing disease severity was 48% among children vaccinated with 3 doses of whole-cell (67%) or acellular (32%)

Pertussis vaccination substantially decrease the severity of breakthrough disease in vaccinated children (3 doses) compared to unvaccinated children

Unvaccinated children twice likely to have severe disease than vaccinated children
Effects of Pertussis vaccination on Disease: Vaccine Efficacy in Reducing Clinical Severity
Preziosi, Marie-Pierre, et.al. Clinical Infectious Disease 2003


DTaP (Diphtheria, tetenus toxoid and acellular
Pertussis)
 contain inactivated PT and 2 or more other bacterial components (FHA, Pn, and Fim 2 and 3)

4 doses during the 1 st 2 years of life

2,4,6 and 15-18 months

5th dose of DTaP recommended for children at 4-6 yr of age


Tdap (Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine, adsorbed)

Preferred age for Tdap vaccination is 11-12 yr

Pregnant adolescents who are in their 2nd or 3rd trimester

All adolescents 11-18 yr of age who received Td, but not Tdap, should receive a single dose of Tdap to provide protection against pertussis


Timing of maternal Tdap immunization is important
– administered during the third trimester to have maternal pertussis antigen-specific IgG levels at their peak

Immunization with DTaP or aP vaccines is not recommended in newborns -- controversial
Pertussis re-emergence in the post-vaccination era
Chiappini et al. BioMedCentral Infectious Disease 2013


Providing indirect protection to infants who are too young to be immunized or protected by vaccine through immunization of their parents and other family members, caregivers and close contacts
Pertussis re-emergence in the post-vaccination era
Chiappini et al. BioMedCentral Infectious Disease 2013


Contributes to increase herd immunity

Reduce transmission of pertussis to susceptible population

Reduce reservoir of pertussis within population and indirectly prevent pertussis case in infants and young children
Pertussis re-emergence in the post-vaccination era
Chiappini et al. BioMedCentral Infectious Disease 2013


Pertussis among health-care personnel has been reported to be 1.7 times higher than the general population

Health-care personnel who have direct contact with patients should receive single dose of TdaP as soon as feasible, if they have not previously received
TdaP
Pertussis re-emergence in the post-vaccination era
Chiappini et al. BioMedCentral Infectious Disease 2013


Patient follow up at OPD – well, active

Received her first dose of DPT, OPV, and
Hepatitis B

Relatives were educated regarding the importance of immunization as well as proper hygiene to stop the vicious cycle of transmission


A case of 6 month old unimmunized infant who presented with subacute cough with paroxysms, who after a nasopharyngeal swab PCR was confirmed with Bordetella pertussis

Started on Azithromycin per orem and eventually discharged well and stable

Recommendations for management of pertussis

Emphasized the importance of immunization on preventing vicious transmission cycle