WHO Operational Protocols Diphtheria PDF
WHO Operational Protocols Diphtheria PDF
WHO Operational Protocols Diphtheria PDF
Probable Case2
A person with an illness characterized by laryngitis or pharyngitis or tonsillitis, and an
adherent membrane of the tonsils, pharynx and/or nose OR gross lymphadenopathy
1
http://www.who.int/immunization/policy/position_papers/wer_31_diphtheria_updated_posit
ion_paper.pdf?ua=1
2
http://apps.who.int/iris/bitstream/10665/68334/1/WHO_V-B_03.01_eng.pdf?ua=1
Clinical presentations
Symptoms: Initial symptoms include malaise, sore throat and nasal discharge
resembling viral upper respiratory illness (URTI). Symptoms can then progress to
bloody nasal discharge, hoarse voice, cough, and/or pain with swallowing. In children,
this may cause drooling or pooling of secretions. In severe cases, patients may develop
noisy breathing (inspiratory stridor) and shortness of breath. Fever may or may not be
present. Skin can become infected with the diphtheria bacteria (cutaneous diphtheria);
clinically wounds have a grey covering over it. (See differential diagnosis table in
Appendix A).
Look for other serious complications: Within 1-12 weeks, after the initial pharyngeal
phase, some patients may develop myocarditis (congestive heart failure, conduction
abnormalities, and arrhythmias), debilitating neurologic dysfunction (neuropathy of
cranial and peripheral nerves, and/or motor weakness/paralysis), or renal failure.
2
Infection Prevention and Control
Transmission of C. diphtheriae occurs from person to person through respiratory
droplets (i.e. from coughing or sneezing) and close physical contact3.
3
http://www.who.int/immunization/policy/position_papers/wer_31_diphtheria_updated_posit
ion_paper.pdf?ua=1
4
http://www.nicd.ac.za/assets/files/Guidelines_diphtheria_20160322_v2_3(1).pdf
5
http://apps.who.int/iris/bitstream/10665/112656/1/9789241507134_eng.pdf
3
Laboratory diagnosis6:
During outbreak, routine sampling of throat samples is not recommended. However,
collection of samples should be considered in the following situations:
a) when diagnosis is unclear (i.e. swollen neck without adherent pseudo-
membrane);
b) or if suspect antimicrobial resistance.
Material for culture should be obtained by swabbing the edges of the mucosal lesions,
placed in appropriate transport media (Amies or Stuart media in ice packs; or dry swabs
in silica gel satchets) and followed by prompt inoculation onto blood agar and tellurite-
containing media, e.g. Tinsdale media.
Suspected colonies may be tested for toxin production using the modified Elek
immunoprecipitation test for detection of toxin; this standard assay takes 24–48 hours.
A positive culture with toxin-producing C. diphtheriae confirms the etiologic diagnosis.
6
http://www.who.int/immunization/policy/position_papers/wer_31_diphtheria_updated_posit
ion_paper.pdf?ua=1
4
Antitoxin therapy (DAT): Administer as soon as possible.
1. DAT is an equine serum product that is highly effective and the gold standard for
treatment of diphtheria7.
2. DAT should be administered immediately to probable cases with respiratory
diphtheria (sore throat, low grade fever and presence of adherent membrane on
tonsils, pharynx or nose) based on clinical diagnosis. Do not wait for laboratory
diagnosis.
3. Diphtheria toxin that has already entered the host cells is unaffected by DAT.
Therefore, to reduce complications and mortality DAT should be administered as
soon as possible after disease onset (see Appendix D)
4. Due to small risk for a serious allergic reaction to the horse serum (0.6 %
anaphylaxis), perform a sensitization test (i.e. Besredka test8) for all candidate
patients.
5. DAT should be administered in a closely monitored setting with appropriate medical
interventions available, if needed.
6. Pregnant women should not receive DAT.
7. The amount of antitoxin recommended varies with larger amounts recommended for
persons with extensive pseudomembrane, neck swelling, systemic signs and with
longer interval since onset. The dose is the same for children and adults. Do not
repeat dosing9.
If limited availability, then use lower dose range.
7
http://www.who.int/immunization/policy/position_papers/wer_31_diphtheria_updated_posit
ion_paper.pdf?ua=1
8
https://medicalguidelines.msf.org/viewport/CG/english/diphtheria-16689456.html
9
https://www.cdc.gov/diphtheria/downloads/protocol.pdf
5
Antibiotic treatment for probable and confirmed cases: Antibiotics should be
administered as soon as possible.
1. For patients who cannot swallow or are critically ill, use IV or IM preparations.
2. For severely ill patients unable to take oral therapy, use IV/IM formulation at the
onset. Once patient improves clinically, stepdown to oral antimicrobials
3. For less sick patients, oral therapy can be used at the onset.
4. Check for penicillin allergy (risk of anaphylaxis from penicillin is very rare).
All persons: 50 mg/kg once daily (maximum 1.2 grams a day)10. Treat for total 14
days.
* Powder for injection: 1 g (=1 million IU); 3 g (=3 million IU) in vial.
Aqueous benzyl penicillin (penicillin G): administer IM or slow IV
All persons: 100,000 units/kg/day administer in divided dose of 25 000 IU/kg every 6
hours. Maximum dose is 4 MIU or 2.4 grams per day11.
For patients who can swallow and are less ill, use oral preparation. Choose one:
Oral phenoxymethylpenicillin V
Oral azithromycin
For children: 10-12 mg/kg once daily (max. 500 mg/day). Treat for total of 14 days.
For adults: 500 mg once daily. Treat for total of 14 days.
Note: There is no data to support the exact duration required for azithromycin
10
http://www.who.int/medicines/publications/essentialmedicines/20th_EML2017_FINAL_
amendedAug2017.pdf?ua=1
11
https://medicalguidelines.msf.org/viewport/CG/english/diphtheria-16689456.html
12
https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/dip.pdf
13
http://www.nicd.ac.za/assets/files/Guidelines_diphtheria_20160322_v2_3(1).pdf
6
Admission criteria/patient disposition (see appendix A)
Patients with a diagnosis of probable or confirmed Diphtheria and with severe
symptoms will require admission to a facility capable of dealing with the respiratory and
systemic complications as well as isolation for first 48 hours. This includes national
hospital’s and Type 2 or Type 3 Field hospitals (facilities with inpatient and surgical
capacity, and the ability to provide high level nursing care, experienced medical and/or
infectious disease doctors, along with anaesthetic and surgical specialists).
Patients with probable diphtheria but mild symptoms require at least 48 hours isolation
but can be discharged within 48 hours of treatment commencing if clinically well
enough. Isolation via cohort versus individual isolation needs to be managed at a facility
level, but cross infection to those without diphtheria may occur in mixed wards, and a
flow within a facility will need to be designed to allow early discharge of the well, and
admission to a lower level isolation after 48 hours for those who have medical reasons
to remain in the clinic or hospital, but with less risk of infecting others after 2 days of
treatment.
Co-location of severe and mild patients should be considered, and criteria and methods
for referral established, given the risk of some mild cases worsening. All cases in the
initial phase of admission (48 hours) require 2-4 hourly review and close observation,
particularly in the very young.
If patient shows any sign of inspiratory stridor, fast respiratory rate, chest indrawing,
restlessness, lethargy, or cyanosis, then call for help and proceed with airway
management.
14
http://www.who.int/maternal_child_adolescent/documents/child_hospital_care/en/
15
http://www.who.int/maternal_child_adolescent/documents/paediatric-emergency-
triage-update/en/
7
2. Administer oxygen if there is incipient airway obstruction and securing airway is
deemed necessary and soon to be performed or if SpO2 < 90%.
Manage shock
1. A child with all 3 signs of shock (delayed CR > 3 seconds + weak and fast pulse +
cold extremities or frank hypotension) needs careful resuscitation. Because shock
can be due to sepsis or cardiac failure, it is imperative to look for signs of cardiac
failure. In addition, also check if child has severe malnutrition. If there are no signs
of cardiac failure and/or fluid overload (absence of crackles, hepatomegaly and
edema), then give gentle fluid bolus. If suspect shock is due to heart failure, then
8
use inotropes (such as dopamine or adrenaline) and do not administer fluids. Refer
to WHO IMCI Handbook for sick children.
Myocarditis (may occur 2–7 weeks after the onset of illness) can present with a weak,
irregular pulse and evidence of heart failure. Treat with supportive therapies according
to national standards.
Neurologic paralysis (may occur 1 to 3 months after the onset of the disease) and can
lead to difficulty with swallowing (paralysis of the soft palate), vision (ocular motor
paralysis), breathing (paralysis of respiratory muscles) and ambulation (limb paralysis).
Treat with supportive therapies according to national standards.
16
https://www.cdc.gov/diphtheria/downloads/close-contacts.pdf
9
5. Administer antibiotics for prophylaxis.
Choose one of the following antibiotics for prevention:
IM benzathine penicillin: a single doseii
For children aged ≤ 5 years: administer 600 000 units
For those > 5 years: administer 1 200 000 units
Oral erythromycin
For children: 40 mg/kg/day, administered in divided dose, 10 mg per dose, every 6
hours
For adults: 1 g/day for adults, administered in divided dose, 250 mg per dose
every 6 hours
Treat for total 7 days
Oral Azithromycin
Children: 10-12 mg/kg once daily, to a max of 500mg/day. Treat for total 7 days
Adults: 500mg once daily. Treat for total 7 days.
6. Exclude from school or work until 48 hours of antibiotics have been completed
7. Self assess for signs and symptoms of diphtheria for at least 7 days.
8. If person develops any symptom of respiratory tract infection, then seek treatment at
a health centre immediately.
Vaccination:
1. Vaccinate according to WHO strategy. Primary prevention of disease by ensuring
high population immunity through immunization.
2.
Acknowledgements:
This has been peer-reviewed by the following group of international experts.
10
Dr. Kobus Preller, Adult ICU, Cambridge UK
Dr. Helena Rabie, Paediatric ID, South Africa
Dr. Tej Tiwari, National Center for Immunizations and Respiratory Diseases
CDC, Atlanta
Dr. Wilson Were, WHO HQ IMCI
11
Appendix A: clinical pathway
TRIAGE
Yes
Yes No
Respiratory diphtheria is a clinical diagnosis. If the patient has atypical features (i.e.
lacks adherent membrane on the pharynx, tonsils or nares); must also consider
alternative etiologies.
13
Appendix C: Hand washing
Hand hygiene must be performed before and after any contact with patients and after
contact with contaminated items or surfaces. Use an alcohol-based product if hands
are not visibly soiled. Wash hands with soap and water when they are visibly soiled or
contaminated with proteinaceous material. The same rubbing technique can be used
with alcohol-based product. This entire procedure can take should take 40-60 seconds
(20-30 for alcohol-based hygiene).
14
Appendix D. How to deliver diphtheria antitoxin (see package insert)
General information for family/patient: DAT is an equine serum product that is highly
effective and the gold standard for treatment of diphtheria. Antitoxin is used to stop the
damaging effect of the toxin and prevent the life-threatening manifestations of diphtheria
infection. However, there is small risk of serious allergic reaction: < 0.6 % anaphylaxis,
4% fever, and 8.8% serum sickness.
Dose: The amount of antitoxin recommended varies with larger amounts recommended
for persons with extensive local lesions and with longer interval since onset. The dose is
the same for children and adults. Do not repeat dosing.
If limited availability, then use lower dose.
Route: The IV route is the preferred route of administration of DAT, especially in severe
cases. The antitoxin dose should be mixed in 250 –500 mL of normal saline and
administered slowly over 2 – 4 hours, closely monitoring for anaphylaxis. The antitoxin
may be given IM in mild or moderate cases.
Procedure:
1. HCW uses contact and droplet precautions: gloves, long-sleeved gown, surgical
mask and eye protection.
2. Monitor patient vital signs: BP, HR, RR, SpO2, mental status, before and after
administration.
3. Perform sensitization testing
15
Sensitization testing: use the Besredka method
a) Inject 0.1 ml SC and wait 15 minutes. If there is no reaction then inject further
0.25 ml SC. If no reaction after 15 minutes, then inject remainder IM or IViv. This
test method is simple and has been used safely in outbreak settings in South
Africa.
b) If patient demonstrates sensitivity on testing, then do not administer entire dose.
Proceed with desensitization according to CDC protocol
https://www.cdc.gov/diphtheria/downloads/skintest-guide.pdf
5. Treatment of anaphylaxis
If anaphylaxis occurs, STOP infusion.
1. Call for help.
2. Assess the airways, breathing and circulation. Start emergency treatments
– If the child is not breathing, check pulse. If no pulse, start basic life support and
give five rescue breaths with a bag-valve mask and 100% oxygen.
3. Give adrenaline (1:1000, 1mg/ml) IM immediately:
0.15 ml of 1:1000 to children < 6 years, repeat every 5 minutes as necessary
0.3 ml of 1:1000 to children 6-12 years, repeat every 5 minutes as necessary
0.5ml of 1:1000 epinephrine to adolescents and adults, repeat every 5 minutes
as necessary
4. Ensure stabilization of airway, breathing and circulation.
Get IV/IO access, give 100% oxygen, give crystalloid fluid (20 ml/kg IV) rapidly
for shock, nebulized salbutamol for wheezing
5. Also give antihistamine and steroids (i.e. prednisolone 1 mg/kg).
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Appendix E. How to approach airway management in patients with severe
respiratory diphtheria
Emergent: If child has a low saturation, SpO2 < 90-94%, lethargy or cyanosis, these
are ominous signs (emergency signs) in patient with upper airway obstruction and the
airway must be secured emergently.
Urgent: If a child with respiratory diphtheria has any signs of respiratory distress, such
as inspiratory stridor, restlessness, fast respiratory rate, chest wall indrawing, accessory
muscle use, this is urgent situation, proceed to secure airway as soon as possible.
In both cases, if there if there is an experienced doctor with difficult airway management
skills and appropriate equipment, attempt an oral intubation using difficult airway
algorithm.
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18
Basic Preparation for airway intervention
Staff: The management of upper airway obstruction due to diphtheria is best done by a
multi-disciplinary team: anaethestist (experience with paediatric, if possible), a surgeon
(ears, nose throat specialist, if possible), intensivist or emergency medicine specialist. If
these specialists are not available, then the most experienced doctors and nurses
should be present.
Check equipment: ensure all equipment is available, checked and working. This
includes: suction, oxygen (BVM), airways (tracheal tubes of appropriate size, oral
airways, various blades); medicines (sedatives), functioning IV and crystalloid fluid.
Also available should be locally available difficult airway cart: This includes: bougie,
video laryngoscope (if available), fiberoptic scope (if available), needle cricoithyrotomy
“kit”, end-tidal CO2 monitor. Tape to secure airway once obtained.
Position: Lying the child flat may worsen the obstruction. So be prepared. Do not lie
child flat until ready to start procedure.
19
How to perform percutaneous needle cricothyroidotomy or “needle cric”
Needle cricothyroidotomy is indicated as a life-saving, last-resort procedure in children
younger than 10 years who have upper airway obstruction, and the child presents or
progresses to the “can’t intubate, can’t oxygenate” scenario. This procedure can be
performed by a paediatrician, intensivist, anaesthetist, emergency physician, general
surgeon or family physician. After inserting the needle cric, then need to arrange child
to be transported quickly to hospital with surgeon that can perform tracheostomy within
60 minutes.
Preparation: Pre-assemble the “needle cric kit” and have available in the resuscitation
area. The simplest equipment, appropriate for use in infants, consists of the following:
o 14G over-the-needle catheter
o To connect to BVM: a 3.0-mm ETT adapter coupled with an IV extension set
(These can be obtained commercially or constructed by cutting off 6 inches of distal
IV tubing and inserting a 2.5 m adapter into the opening (below)
o To connect directly to oxygen: 3- or 5-mL syringe with side port “hole” to allow
exhalation, with oxygen tubing inserted inside with a “tight fit” (below)
o It is good practice to preassemble the kit, place it in a clear bag, seal the bag, and
tape it in an accessible place in the resuscitation area.
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2. Position: Place the child in the supine position with the head extended over a towel
under the shoulder. This forces the trachea anteriorly such that it is easily palpable
and can be stabilized with two fingers of one hand. The key to success is strict
immobilization of the trachea throughout the procedure.
3. Anatomy: “Carefully palpate the cricothyroid membrane.” In reality, it is difficult to do
this in an infant and is not essential. Indeed, in smaller children, it may be impossible
to precisely locate the cricothyroid membrane, so the proximal trachea is utilized for
access (hence the name percutaneous needle tracheostomy [PNT] vs. “needle
cric”). The priority is an airway and provision of oxygen. Complications from inserting
the catheter elsewhere into the trachea besides the cricothyroid membrane are
addressed later.
4. Sterile technique: Clean skin and wear sterile gloves.
5. Needle insertion: Consider the trachea as one would a large vein, and cannulate it
with the catheter-over-needle device directed caudally at a 30° angle. Aspirate air to
ensure tracheal entry and then slide the catheter gently forward while retracting the
needle.
6. Connect adaptor: The catheter can be attached either to a 3.0 mm ETT adaptor to
provide bag ventilation (if available). Or, can be attached directly to oxygen supply.
Both are described below:
Attach to BVM: Attach 3.0-mm ETT adapter to the hub of the catheter and
commence bag ventilation. The provider will note exaggerated resistance to
bagging. This is normal and is related to the small diameter of the catheter and the
turbulence created by ventilating through it. It is not generally the result of a
misplaced catheter or poor lung compliance secondary to pneumothorax. It is helpful
to practice BMV through a catheter to experience the feel of this increased
resistance. The operator must allow for full expiration through the patient’s glottis
(if not completely obstructed) and not through the catheter in order to prevent
breath-stacking and barotrauma. This can be accomplished by watching for the
chest to fall after inspiration. The required pressures are well above the limits of the
pop-off valve; therefore, it must be disabled in order to permit gas flow through the
catheter. A secondary source of oxygen can be put over the mouth.
21
Attach to oxygen source directly (no BVM): If you have three-way stopcock, then
attached to end of catheter that should already be connected to oxygen tubing. The
three-way stopcock will allow for inspiration of oxygen and exhalation. Alternatively,
attach the 2-5 ml syringe with exhalation side port, already connected to oxygen
tubing. For inhalation, occlude exhalation side-port for one second, then allow
exhalation for 3-4 seconds (look at chest wall rise and fall to determine ventilation.
Always make sure the exhalation side-port is not blocked by oxygen tubing.
1. After securing the airway, firmly secure tube to avoid accidental displacement, as
this could be fatal.
2. Care for child in an intensive care unit with appropriately trained staff and
monitoring.
3. The provision of humidified oxygen and ventilation will depend on available
resources (i.e. manual bag ventilation, mechanical ventilation or oxygen therapy)
and severity of hypoxemia. If aspiration has occurred, CPAP may be necessary.
4. Manage secretions with careful suctioning and humidification to prevent tube
obstruction from sloughed, thick pseudomembranes.
22
APPENDIX F: Specimen collection, storage and transportation
Laboratory confirmation of diphtheria is useful for diagnosis of clinically suspected cases in the
early phases of a response, or when diagnosis is equivocal. Specimen of choice is a throat swab
that should be collected as early as possible during the course of illness of the suspected cases.
Nasopharyngeal swab is also considered as a good specimen for diphtheria diagnostics
especially in infants or small children. The chances of positivity fall rapidly after 2-3 weeks of
onset or by use of appropriate antibiotics. The diphtheria bacteria have fastidious growth
requirements and are susceptible to drying therefore, the use of transport media is
recommended to enhance positivity of laboratory tests. The prerequisites for sample collection
and condition of sample storage and transportation for diphtheria is described in the table
below.
23
Amies Transport media with or without charcoal
Zip lock bag
Labels
Laboratory request form
Throat swab sample collection:
Use any throat swab made up of cotton, polyester or Dacron
Label the specimen tube with the unique identification code, patient’s name and date of
collection
Check the expiry date on the tube and transport media
Swab the inflamed area of tonsils, and posterior pharynx. If membrane is visible then
rub the swab beneath the membrane
Piece of membrane can also be collected on the swab
Immediately place the throat swab sample in the Amies transport media
Procedure to use Amies transport media:
o immediately insert the swab till the bottom of the media
o if capped swab then throw the cap of the tube
o if un capped swab – then cut the shaft of the swab to fit into the tube and cap it
securely
Ship the sample to the laboratory at 2-8OC
Nasopharyngeal swab sample collection:
Obtain a thin flexible nasopharyngeal swab made up of Dacron or nylon
Label the specimen tube with the unique identification code, patient’s name and date of
collection
Check the expiry date on the tube and transport media
Have patient sit with head against a wall or a support as patients have a tendency to pull
way during this procedure
Explain the procedure to the parents or patient
Measure the distance between anterior nares to the lower lobe of the ear of one side
Mark the swab with half of the above measured distance
Ask the patient to blow the nose forcefully to remove any mucous plug
Position the head slightly upwards and insert the swab along the base of the nose up to
the distance marked. Avoid insertion of swab in upward direction
Do not force swab if obstruction is encountered before reaching the nasopharynx.
Remove swab and try the other side
Try to leave the swab in place for 5-10 seconds to increase sensitivity
Immediately place the swab in Regan-Lowe transport media/Amies transport media
with charcoal and tighten the cap of specimen collection container. It is recommended
to wrap tape around cap to prevent any leakage
Ship at 4OC
24
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CDC ‘Epidemiology And Prevention of Vaccine-Preventable Diseases’, The Pink Book:
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