Lecture 11, PHC 3

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Community and Family Medicine Department

FMHS/UST
WHOOPING COUGH (PERTUSSIS)
vDefinition:
• Pertussis, also known as whooping cough, is a highly contagious respiratory disease. It
is caused by the bacterium Bordetella pertussis.

• Pertussis is known for uncontrollable, violent coughing which often makes it hard to
breathe.
• After cough fits, someone with pertussis often needs to take deep breaths, which
results in a “whooping” sound.
• Pertussis can affect people of all ages but can be very serious, even deadly, for babies
less than a year old.
• Whooping cough is called a 100-hundred-day cough due to the long duration of the
disease.

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GLOPAL BURDEN OF PETRESSIS
• Pertussis is endemic worldwide, with epidemic peaks every 2–5 years, and is highly
contagious.
• Increase of cases of pertussis - Multi-country -weekly Eureapean Bullten report 2023;
• In recent months, several EU/EEA Member States have reported an increase in the
number of pertussis cases compared to pre-pandemic time periods, potentially linked
to lower circulation during COVID-19 pandemic,and a consequence of suboptimal
vaccination uptake in certain groups during the COVID-19 pandemic.

• According to WHO report of 2021, the number of cases globally were increased. 3457 in
Australia, 4475 in China, 2390 in Denmark, 29 in Pakistan, 136 in Malaysia.
• In meditation region, Jordan, Bahrain & Qatar there were no cases, 224 in Syrian of
Arab republic 224, 73 in Sudan, 24 in united if Arab Emirates.

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IN YEMEN
• Since epidemiological week 1 of 2020, Yemen has been experiencing a continuous
outbreak of pertussis and 13 out of 23 governorates were affected over that time period.
• From week 1 of 2020 to week 30 of 2021, a total of 3013 suspected cases and 6
associated deaths were reported (CFR: 0.2%)

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CASE DEFINITION
vClinical Criteria:
In the absence of a more likely diagnosis a cough illness lasting ≥2 weeks, with at least one
of the following signs or symptoms:
Paroxysms of coughing, OR
Inspiratory whoop, OR
Post-tussive vomiting, OR
Apnea (with or without cyanosis)

vLaboratory Criteria
Confirmatory laboratory evidence:
Isolation of Bordetella pertussis from a clinical specimen
Positive polymerase chain reaction (PCR) for B. pertussis

vEpidemiologic Linkage:
Contact with a laboratory-confirmed case of pertussis. 6

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v Case Classification:
§ Probable:
In the absence of a more likely diagnosis, illness meeting the clinical criteria
OR
Illness with cough of any duration, with At least one of the following signs or symptoms:
Paroxysms of coughing, OR Inspiratory whoop, OR
Post-tussive vomiting, OR Apnea (with or without cyanosis)
AND
Contact with a laboratory confirmed case (epidemiologic linkage)

§ Confirmed:
Acute cough illness of any duration with
Isolation of pertussis from a clinical specimen, OR
PCR positive for B. pertussis

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PATHOGENESIS

1. Pertussis is primarily a toxin-mediated disease and it transmittited to our bodies by


aerosols.
2. The bacteria attach to the cilia of the respiratory epithelial cell and multiplication with
increasing mucus secretion.
3. Then the bacteria produce toxins that paralyze the cilia.
4. Cause inflammation of the respiratory tract, which interferes with the clearing of
pulmonary secretions

Note:
• Symptoms may be milder and paroxysmal cough may be absent, particularly in previously
vaccinated individuals.

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CLINICAL FEATURES
v There are three stages to the clinical course of pertussis:
1. Catarrhal (lasting for 1-2 weeks)
2. Paroxysmal (lasting for 1-6 weeks)
3. Convalescent (it may weeks to months or (8 wks to 12 months)

Stage Clinical Features


Stage 1: Characterized by:
Catarrhal Coryza
(insidious Low-grade fever
onset) Mild, occasional dry cough (initially intermittent which gradually becomes
more severe)
Stage 2: Characterized by:
Paroxysmal • Paroxysms of numerous, rapid coughs due to difficulty expelling thick mucus
Dr. Duaafrom the tracheobronchial tree 9

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Stage Clinical Features
Stage 2: • Long inspiratory effort accompanied by a high-pitched “whoop” at the
Paroxysmal end of the paroxysms
• Cyanosis
• Vomiting and exhaustion
Paroxysmal attacks:
• Occur frequently at night, with an average of 15 attacks per 24 hours
• Increase in frequency during the first 1-2 weeks, remain at the same
frequency for 2-3 weeks, and then gradually decrease
Stage 3: Characterized by:
Convalescent
• Gradual recovery
• Less persistent, paroxysmal coughs that disappear in 2-3 weeks
• Paroxysms often recur with subsequent respiratory infections for many
months after the onset of pertussis.
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PERTUSSIS

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EPIDEMIOLOGICAL DETERMINANTS

PERTUSSIS CHARACTERISTICS
Agent factors
Agent The bacterium Bordetella pertussis
Reservoir Case/ subclinical case
Incubation period 1-2 weeks
Period of infectivity During catarrhal stage up to about 3 weeks after the start of
paroxysmal cough
Infective material Nasopharyngeal and bronchial secretions
Stable The bacterium survives only for very short periods outside
the human body
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EPIDEMIOLOGICAL DETERMINANTS
PERTUSSIS CHARACTERISTICS
Host factors
Age Infant and children under 5 years (preschool diseases)
Sex Both
Immunity One attack of disease will give good immunity
Secondary attacks may occur in immunocompromised persons
Environmental factors
Environment All seasons but more in winter and spring
Mode of transmission 1. Direct droplet infection
2. Indirect through use of freshly contaminated article and
fomites belonging to patient
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RISK FACTORS

1. Non-vaccination in children.
2. Infants who are younger than age 12 months who are unvaccinated.
3. Contact with an infected person.
4. Epidemic exposure.
5. Pregnancy.
6. Poor socio-economic class & overcrowded

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COMPLICATIONS & PROGNOSIS
1. Infants and Children:
• Complication common among those who have not received all the recommended
vaccines but the prognosis is good in those who complete their vaccinations.
• Hospitalization is most common in infants younger than 6 months of age.
• Of those infants with pertussis who need treatment in a hospital approximately:
68% will have apnea, 23% get pneumonia, 1.2% will have seizures
1% will die, 0.4% will have encephalopathy (due to hypoxia from coughing or from toxin).

• Other complications can include:


• Anorexia, dehydration, difficulty sleeping, epistaxis, hernias, otitis media, and urinary
incontinence.

• More severe complications can include:


• Refractory pulmonary hypertension, Pneumothorax
• Rectal prolapse 17

• Subdural hematomas 17
2. Adolescents and Adults:
• Complications are usually less severe in this older age group, especially in those who
received pertussis vaccines.
• Clinicians diagnosed pneumonia in 2% of each group.
• The most common complications in another study of adults with pertussis were:
Weight loss
Urinary incontinence
Syncope
Rib fractures from severe coughing
• Other complications can include anorexia, dehydration, epistaxis, hernias, and otitis
media.

• More severe complications can include:


Encephalopathy
Pneumothorax
Rectal prolapse
Subdural hematomas 18
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Seizures
DIAGNOSIS
1. Blood pictures:
• Leukocytosis with absolute lymphocytosis and an increase of neutrophils suggests a
secondary bacterial infection.

2. Specimen Collection:
• Determining who has pertussis can be difficult. Whenever possible, clinicians should
obtain a nasopharyngeal (NP) swab or aspirate from all persons with suspected cases.
• The same specimen can be used both for culture and polymerase chain reaction (PCR).

3. Diagnosis Confirmation:
• Scientists consider culture the gold standard because it is the only 100% specific method
for identification. Other tests that can be performed include polymerase chain reaction
(PCR) and serology.
• Culture it is particularly useful for confirming pertussis diagnosis19 when you suspect an
outbreak.
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TREATMENT
• Treat appropriately for pertussis; Because pertussis may progress rapidly in young infants,
treat suspected and confirmed cases promptly. However, treatment is effective in
catarrhal stage and ineffective if started late in the course of illness.

• The recommended treatment or chemoprophylaxis of pertussis are:


1. Macrolides:
First line: Azithromycin
Second line: Clarithromycin or Erythromycin

2. Clinicians can also use Cotrimoxazole in case of allergy to macrolides.


• Clinicians should strongly consider treating prior to test results if any of the following are
present:
Clinical history is strongly suggestive of pertussis
The person is at risk for severe or complicated disease (e.g., infants)
Contact with someone that is considered at high risk of serious disease 20 (e.g., pregnant
women)
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PREVENTION
1. General measures of poor ventilation and prevention of overcrowding and health
education
2. Specific measures of active immunization by DPT. In Yemen, three doses are given in the
2nd, 3rd, and 4th months of the first year, while the 4th dose is given at 18 months.

For pregnant women: should take vaccination between 27- 36 weeks of gestation.

3. Clinicians can also use preventive antibiotics to protect people who have been exposed
and are at high risk of developing severe pertussis.

• All adults who haven’t been previously vaccinated with DPT should get a DPT vaccine
followed by either a Td or DPT vaccine every 10 years.
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CONTROL
v Measure to cases: v Measure to contacts:
1. Early diagnosis/ notification 1. Listing
2. Isolation 2. Surveillance for two weeks
3. Treatment with antibiotics and examination for
4. Disinfection of the discharge from nose and throat d e te c t i o n o f m i s s e d a n d
atypical cases.
v Measure to the environment: 3. A booster dose of DPT for
Concurrent and terminal disinfection. children below 4 years.

• Why intensive surveillance requires for whooping cough cases?


• Due to high infectivity, short incubation period, greater transmission risk, and
increased morbidity and mortality especially among those under-five years of age.
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DIPHETERIA
DIPHTHERIA
v Definition:
• It is an acute bacterial disease of the tonsils, pharynx, larynx, nose, skin, and sometimes
the conjunctivae or genitalia.
• It caused by toxin-producing strains of Corynebacterium diphtheria.

v Diphtheria is caused by three Corynebacterium species, namely:


• Corynebacterium diphtheriae, Corynebacterium ulcerans, and Corynebacterium
pseudotuberculosis.
• They are responsible for the production of diphtheria toxin (DT), a potentially lethal
exotoxin leading to pseudomembrane formation and to the systemic signs of disease.

v C. diphtheriae causes classic human diphtheria and carriage is almost exclusively


restricted to people, While, C. ulcerans and C. pseudotuberculosis are mainly veterinary
organisms.
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DIPHTHERIA

• Non-toxin-producing strains of C. diphtheriae can also cause disease. It is generally less


severe, potentially causing a mild sore throat and, rarely, membranous pharyngitis.
Invasive disease, including bacteremia and endocarditis, has been reported for non-
toxin-producing strains of C. diphtheriae.

• Vaccination is highly protective against disease caused by toxin-producing strains, but


does not prevent the carriage of C. diphtheriae, regardless of toxin production status.

• C. diphtheriae is an aerobic gram-positive bacillus. Toxin production (toxigenicity) occurs


only when the bacillus is itself infected (lysogenized) by a specific virus (bacteriophage)
carrying the genetic information for the toxin (tox gene).

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GLOBALLY
• In Europe: From January 2022 to August 2023, 281 cases of diphtheria were confirmed
in EU/EEA countries, with most cases in migrant-related facilities (Outbreak News Today,
2023). The ECDC reported most cases in Germany and Switzerland. The cases were
caused by Corynebacterium diphtheriae and 53 by Corynebacterium ulcerans.
• The age range of cases was 0 to 92 years. Of the 228 cases, 199 had the cutaneous form,
18 had the respiratory form, three had both, and three had the nasal form. Three
deaths were attributed to C. diphtheriae and one to C. ulcerans.

• Ethiopia is the top country by diphtheria cases in the world. As of 2020, diphtheria
cases in Ethiopia was 5,267 that accounts for 52.11% of the world's diphtheria cases.
• The top 5 countries (others are India, Indonesia, Viet Nam, and Yemen) account for
93.53% of it.
• The world's total diphtheria cases was estimated at 10,107 in 2020.
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IN YEMEN
• In Diphtheria is a health problem due to incomplete immunization coverage.

• Reports of diphtheria cases in Yemen (to 16 November 2023) are 57% higher than in 2021
and 2022.

• Cases have risen gradually since 2021, with a significant increase noted in 2023. So far this
year, 1671 suspected diphtheria cases have been reported in the country, with 109
associated deaths, compared with 1283 cases reported in the whole of 2022.

• In response to the current increase in cases, WHO is working to supply Yemen’s Ministry of
Public Health and Population with an urgent quantity of 2200 vials of diphtheria antitoxin,
which will be distributed to the most affected areas. Due to the complexities of the Yemen
situation, however, only 220 vials have been delivered to date, whereas the global
shortage of diphtheria antitoxin affects its availability and increases prices.
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CASE DEFINITION & CLASSIFICATION
v Clinical case definition:
• An upper respiratory tract illness characterized by sore throat, low-grade fever, and an
adherent membrane of the tonsil(s), pharynx, and/or nose without other apparent cause
(as reported by a health professional)
vLaboratory criteria for diagnosis:
• Isolation of Corynebacterium diphtheriae from a clinical specimen.
vProbable:
• Meets the clinical case definition, is not laborator y confirmed, and is not
epidemiologically linked to a laboratory- confirmed case.
vConfirmed:
• Meets the clinical case definition and is either laboratory confirmed or epidemiologically
linked to a laboratory- confirmed case.
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CLINICAL FEATURES
v The bacilli multiply locally, usually in the throat, and elaborate a powerful exotoxin that is
responsible for:
1. The formation of a greyish or yellowish membrane commonly over the tonsils, pharynx,
or larynx with well-defined edges, and the membrane cannot be wiped away.
2. Marked congestion, oedema, or local tissue destruction.
3. Enlargement of the lymph nodes.
4. Signs and symptoms of toxemia.
• Diphtheria can involve almost any mucous membrane.

• For clinical purposes, it is convenient to classify diphtheria into types of manifestation,


depending on the site of the disease:
• Respiratory diphtheria • Cutaneous diphtheria
1. Nasal diphtheria
2. Pharyngeal and tonsillar diphtheria
3. Laryngeal diphtheria 29

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CLINICAL FEATURES
v Respiratory diphtheria has a gradual onset and is characterized by:

1. Mild fever
2. Sore throat
3. Difficulty swallowing
4. Malaise
5. Loss of appetite
6. Hoarseness (if the larynx is involved) stridor heard on inspiration

• The hallmark of respiratory diphtheria is a pseudomembrane that appears within 2–3


days of illness over the mucous lining of the tonsils, pharynx, larynx, or nares and that
can extend into the trachea.
• Fatal airway obstruction can result if the pseudomembrane extends into the larynx or
trachea or if a piece of it becomes removed.
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RESPIRATORY DIPHTHERIA

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CUTANEOUS DIPHTHERIA

• Cutaneous diphtheria may present as:

1. The bacteria can infect the skin, causing


open sores or ulcers. with clearly
demarcated edges and membrane.

2 . T h e sy s t e m i c c o m p l i c a t i o n s f r o m
cutaneous diphtheria with toxigenic strains
appear to be less than from other sites.

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EPIDEMIOLOGICAL DETERMINANTS
DIPHTHERIA CHARACTERISTICS
Agent factors
Agent Coryne-bacterium diphtheria bacilli
Reservoir Cases or carrier
Incubation period 2–6 days (range: 1–10 days)
Period of infectivity Unless treated, the period of infectivity may vary from 14 to 28
days from the onset of the disease, but carrier may remain much
longer time
Infective material Nasopharyngeal secretions, discharges from skin lesions,
contaminated fomites and possibly infected dust
Stable The bacteria is sensitive to penicillin & killed by heat and
chemical agents. They may survive for short periods in dust and
fomites
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EPIDEMIOLOGICAL DETERMINANTS
DIPHTHERIA CHARACTERISTICS
Host factors
Age Affects children aged 1 to 5 years
Sex Both
Immunity Lifelong immunity is usually, but not always. Immunization dose
not prevent carrier state
you need booster shots of the diphtheria vaccine to help you
maintain your immunity. That's because immunity to diphtheria
fades with time.
Environmental factors
Environment All seasons but more in winter
Mode of transmission 1. Airborne droplets
2. Contaminated personal or household items
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RISK FACTORS

1. Lack of immunization.
2. Infants who are younger than age 12 months who are unvaccinated.
3. History of contact with diphtheria patients.
4. Presence of skin lesions.
5. History of chronic health conditions.
6. History of travel to areas endemic for diphtheria.
7. Overcrowding and bad ventilation
8. Exposure to poor sanitary conditions.
9. Poor personal hygiene.
10.Sharing of fomites with a person suffering from diphtheria.

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COMPLICATION
vLeft untreated, diphtheria can lead to:
1. Breathing problems:
The toxin of bacteria cause damages tissue in the immediate area of infection — usually, the
nose and throat and produces a tough, gray membrane made up of dead cells, bacteria and
other substances. This membrane can obstruct breathing.
2. Heart damage:
The toxin may spread through the bloodstream and damage other tissues in the body. It can
damage the heart muscle, causing such complications as inflammation of the heart muscle
(myocarditis). At its worst, myocarditis can lead to heart failure and sudden death.
3. Nerve damage (Peripheral neuritis) :
The toxin can also cause nerve damage. Typical targets are nerves to the throat, where poor
nerve conduction may cause difficulty swallowing. Nerves to the arms and legs also may
become inflamed, causing muscle weakness.
4. Kidney problems. 36

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PROGNOSIS

• Cure with treatment, most people with diphtheria survive these complications, but
recovery is often slow.
• Diphtheria is fatal about 5% to 10% of the time.
• Rates of death are higher in children under age 5 or adults older than age 40.
• For some people, respiratory diphtheria can lead to death.
• A bout 1 in 10 patients with respiratory diphtheria die.
• Without treatment, up to half of patients can die from the disease.

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DIAGNOSIS
1. Clinical manifestation:
• Diphtheria should be suspected in differential diagnosis of bacterial and viral pharyngitis,
Vincent’s angina, infectious mononucleosis, oral syphilis, and candidiasis.
• Presumptive diagnosis is based on observation of a whitish membrane, especially if
extending to the uvula and soft palate, in association with tonsillitis, pharyngitis or
cervical lymphadenopathy, or serosanguinous nasal discharge.

2. Culture: they can swab the back of the throat or nose and test it for the bacteria that
cause diphtheria also take a sample from an open sore or ulcer.
• Diagnosis of diphtheria is confirmed by culture of the organism from the specimen and by
demonstrating toxin production using an immunoprecipitation reaction (the modified Elek
test).
• ELEK test is the gold standard for the detection of the major virulence factor diphtheria
toxin (DT) in toxigenic corynebacteria.
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Elek test
• The Elek test is an in vitro immunoprecipitation (immunodiffusion) test to determine
whether or not a strain of Corynebacterium diphtheriae is toxigenic.
• We use:
1. known toxigenic C.diphtheria
2. known non-toxigenic C.diphtheria
3. Filter paper saturated with antitoxin of C.diphtheria
4. Serum agar
5. unknown (patients isolate C. diphtheria).

• Procedure:
• A test strip of filter paper containing diphtheria antitoxin is placed in the center of the
agar plate.
• Strains to be tested (patient’s isolate), known positive and negative toxigenic strains are
also streaked on the agar’s surface in a line across the plate and at a right angle to the
antitoxin paper strip.
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Elek test

• The result: of the reaction was regarded as positive (toxigenic) if the bacteria grow and
make a toxin (poison) as a precipitin line (white line) was formed between the bacterial
plaque and the disk loaded with antitoxin after 24 h of Elek test incubation at 37 °C.

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TREATMENT
• It is important to start treatment (antitoxin) right away if a doctor suspects respiratory
diphtheria before bacteriologic results.

• Diphtheria cases treatment involves:

1. Using diphtheria antitoxin to stop the toxin made by the bacteria from damaging the
body.
• This treatment is very important for respiratory diphtheria infections, but it is rarely used
for diphtheria skin infections.

2. Using antibiotics to kill and get rid of the bacteria, such as penicillin or erythromycin.
• This is important for both diphtheria infections in the respiratory system and on the skin.

• For carriers: treatment with just antibodies such as penicillin or erythromycin.

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PREVENTION CONTROL
General: Measure to case:
1. Measure to prevent overcrowding, proper 1. Confirm the diagnosis
ventilation, adequate nutrition 2. Isolation at fever hospital
2. Health education 3. Notification to local health authority
3. Detecting of carriers among food handlers 4. General treatment supportive therapy with bed
rest
5. Specific treatment: antitoxic sera, antibiotic as
penicillin and erythromycin
6. Disinfection : concurrent and terminal
Specific: Measure to contact:
1. Active immunization by triple antigen DPT 1. Surveillance for all contact
1. Diphtheria- toxoids-antitoxin floccules: Three 2. Immunization the contact
doses at interval 6 weeks, by 0.1 ml deeply 2. Health education
subcutaneous at 2, 3 and 4 months in the first
year

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