Decision No. 2957/QD-BYT 2020 guidance on diagnosis and treatment of diphtheria

DECISION

ON PROMULGATING THE GUIDANCE ON DIAGNOSIS AND TREATMENT OF DIPHTHERIA

---------

THE MINISTER OF HEALTH

Pursuant to the Government s Decree No. 75/2017/ND-CP dated June 20, 2017 on defining the functions, tasks, powers and organizational structure of the Ministry of Health;

Considering the professional council’s meeting minutes dated July 09, 2020 on amending and supplementing the Guidance on the diagnosis and treatment of diphtheria;

At the proposal of the Director of the Medical Services Administration - the Ministry of Health,

DECIDES:

Article 1.Issuing together with this Decision the Guidance on the diagnosis and treatment of diphtheria.

Article 2.The Guidance on the diagnosis and treatment of diphtheria shall be applied in state and private medical examination and treatment establishments nationwide.

Article 3.This Decision takes effect on the signing and issuing date.

Article 4.Mr./Ms.: The Director of the Medical Services Administration; Chief of the Ministry Office; Chief Inspector of the Ministry Inspectorate; Directors and General Directors of Departments and Directorates of the Ministry of Health; Directors of hospitals or institutes with patient beds of the Ministry of Health; Directors of Health Departments of provinces and centrally run cities; Heads of medical units of ministries and branches; Heads of relevant units shall be responsible for the implementation of this Decision./.

GUIDANCE

ON DIAGNOSIS AND TREATMENT OF DIPHTHERIA

(Attached to the Decision No. /QD-BYT of the Minister of Health dated July, 2020)

1. OVERVIEW

Diphtheria is an infectious-toxic disease caused byCorynebacterium diphtheriaebacillus (also called asKlebs-Leofflerbacillus), spreads through respiratory tract and may become an epidemic.  This disease often affects children less than 15 ages and subjects who are not immune to diphtheria because they have not been fully vaccinated. This bacteria often localizes in and damages the upper respiratory tract (including nose, throat, larynx), causes the formation of tough, sticky pseudo-membrane and produces exotoxins that cause systemic intoxication (such as heart, kidney, nerves) and may cause the death due to respiratory obstruction and myocarditis. The disease has the specific treatment with antibiotics and serum anti diphtheriae (SAD) and can be prevented with vaccines.

2. CAUSAL AGENTS

Corynebacterium diphtheriae is a gram positive, rod-shaped, nonmotile, non-capsulated, non spore-forming bacillus with a length of 1 to 9 µm and width of 0.3 to 0.8 µm. The bacillus can be long-lived on the pseudo-membrane and throat of patients. In low light condition, the bacteria can live up to 6 months and be long-lived on toys of affected children, blouses of medical staff, etc. The diphtheria bacteria shall be dead at 58^oC within 10 minutes and under the sunlight within several hours.

3. CLINICAL FEATURES

The most popular types of diphtheria are pharyngeal diphtheria (70%), laryngeal diphtheria (20-30%), nasal diphtheria (4%), ocular diphtheria (3-8%), cutaneous diphtheria, etc.

3.1. Pharyngeal diphtheria

3.1. The incubation period:varies from 2 to 5 days without any clinical symptoms.

3.1. The initial symptom onset:

- Patients often have fever with 37.5^o- 38^oC, sore throat, malaise, weakness, eat less, have bluish skin and nasal discharge from one or both nares with blood or not.

- Throat examination: May see reddish throat reddish throat, translucent white points being pseudo-membranes on one of tonsils. May touch a small and motile node in the neck and there is no pain.

3.1.3. The whole symptom onset:This period occurs in the second to third day of the duration of the disease.

- Body examination: Patients often have fever with 38^o- 38.5^oC, painful swallowing, pale skin, much weakness, loss of appetite, fast pulse, slightly lower blood pressure.

- Throat examination: Pseudo-membranes extend to affect one or both of tonsils; in severe cases, pseudo-membranes extend to affect the uvula and soft palate. Firstly, pseudo-membranes are ivory white; after that, they become straw-colored, are firmly adhere to mucosa, can come off leading to bleeding, they can regrow quickly if dislodged, after only several hours. Pseudo-membranes are tough, insoluble in water. Mucosa surrounding pseudo-membranes is normal.

- The lymph nodes of the jaw become inflamed and edematous. Patients have massive nasal discharge with white nose mucus or pus.

3.2. Malignant diphtheria

It can appear soon, from the 3^rdto 7^thday of the disease. Serious toxic infection illness with high grade fever of 39 - 40^oC, pseudo-membranes extend throughout pharynx and lips. Massive and deformed swollen cervical lymph nodes cause broaden form and may produce soon complications as myocarditis, kidney failure, nerve lesions.

3.3. Laryngeal diphtheria

- Patients rarely affected only laryngeal diphtheria, but pharyngeal and laryngeal diphtheria.

- Clinical illness includes: To be acute laryngitis (to have barking cough, hoarse voice, inspiratory dyspnea and have whistle in the larynx), in the later stage, it can lead to the suffocation.

4. PARA-CLINICAL

4.1. Identifying roots

+ Specimens: To collect the pharyngeal fluid from the edge of the pseudo-membrane area (swabs used to collect specimens shall be stored in Amies or Stuart medium, immediately transported to the laboratory as soon as possible).

+ Staining for diphtheria morphology bacteria:Rod-shaped Gram-positive bacillus (+).

+ Culturing in Blood agar medium, Loeffler selective medium (Tellurite kali) (orCystine tellurite blood agar - CTBA medium) for diphtheria bacteria, identifying diphtheria toxin (TestingToxigenicity by Elek test, for example).

+ Using Polymerase chain reaction technique (PCR) to identify diphtheria toxin gene at conditional establishments.

4.2. Regular tests and monitor, detection of complications

(Blood formula, liver enzymes, cardiac enzymes, urea, creatinine, electrolytes, blood glucose, blood gases if needed, Electrocardiogram (ECG), total urinalysis, Chest X-ray, etc.)

5. DIAGNOSIS

5.1. Suspected case

- Clinical: Having clinical illness of diphtheria, pharyngeal pseudo-membranous lesions.

- Epidemiology: Patients have traveled to and come from areas where there is diphtheria disease or lived in areas there have been diphtheria outbreaks in the last 05 years.

5.2. Definitive diagnosis

Suspected cases accompanied with testing for positive diphtheria bacteria.

5.3. Differential diagnosis

5.3.1. Purulent tonsillitis with a piece of pseudo-membrane dislodged due to many causes such as:

- Group A streptococcus

- Vincent’s Angina

- Epstein-Barr virus (EBV)

- Oral candida

5.3.2. Laryngitis due to other causes

- Viral laryngitis

- Retropharyngeal abscess

- Anaphylaxis

5.3.3. Complications from diphtheria due to other causes

- Myocarditis

- Kidney failure

- Nerve paralysis

6. TREATMENT

6.1. Treatment principles

- Early detection, isolation upon detecting infected case

- Immediately using serum anti diphtheriae (SAD) and antibiotics (penicillin G, erythromycin, azithromycin) to prevent from complications and reduce death

- Monitoring, early detecting and timely handling complications

- Providing comprehensive care to patients

6.2. Specific treatment

6.2.1. Serum anti diphtheriae (SAD)

Using immediately upon suspicion of infection. Dosage of SAD shall be depended on the seriousness of the disease, regardless of the age and weight. It is required to test before injection, if the result is positive, the desensitization method (Besredka) shall be applied

- Pharyngeal diphtheria or laryngeal diphtheria in the first 02 days: 20,000 - 40,000 IU

- Naso-pharyngeal diphtheria: 40,000 - 60,000 IU

- Malignant diphtheria: 80,000 - 100,000 IU

In extensive form, SAD intravenous infusion may be considered (it is required to strictly monitor anaphylaxis signs and prepare for anaphylaxis emergency which may occurs). Infusion methods: To mix the whole SAD in 250 - 500 ml of 0.9% sodium chloride and carry out slowly intravenous administration in 2 to 4 hours.

* Besredka method

a) To inject 0.1 ml of diphtheria serum and wait 15 minutes. If there is no reaction, then inject a further 0.25 ml of diphtheria serum. If there is no reaction after 15 minutes, intramuscular or intravenous injection shall be applied to the rest of the product.

b) If a patient demonstrates sensitivity on testing, then do not administer entire dose. Proceed with desensitization according to the Ministry of Health’s instruction.

6.2.2. Antibiotics

- Penicillin G: 50,000 - 100,000 units/kg/day divided in equal doses, intramuscularly for 14 days, until the pseudo-membrane disappears.

- Or oral Erythromycin: Children: 30 - 50 mg/kg/day; Adults: 500 mg x 4 times/day for 14 days, until the pseudo-membrane disappears.

- Or Azithromycin: Children: 10 - 12 mg/kg/day; Adults: 500 mg/day x 14 days.

6.2.3. Other treatment

- Respiratory support: Airway ventilation (for laryngeal dyspnea of level II, a tracheostomy shall be indicated for airway ventilation). Oxygen therapy shall be early applied if there is any sign of respiratory distress, if oxygen is not helpful, non-invasive/invasive ventilation may be applied, depending on the seriousness of the respiratory distress case.

- Circulation support: To ensure to provide adequate electrolyte water as needed, taking account of hydration if there is high grade fever, shortness of breath and vomiting, etc. In case of shock (cold extremities, signs of capillary refill ≥ 3 seconds, systolic blood pressure < 90 mmHg in adults, urine < 0.5ml/kg/hour) after full hydration (central venous pressure is from 12 - 14 cm H₂O, or invectively measuring the inferior vena cava diameter, etc.), vasopressors should be used to ensure an average blood pressure ≥ 65mmHg and blood lactate < 2 mmol/l. Fluid overload assessment must be noted.

- Electrolyte water balance.

- If a patient show any sign of cardiac arrhythmia (type 2 Second-degree AV block), the temporary cardiac pacemaker may be inserted via skin or through jugular vein.

- For cases of myocarditis treated according to myocarditis regimen, if the myocarditis is severe or there is a cardiogenic shock that does not respond to inotropes, venoarterial extracorporeal membrane oxygenation (VA-ECMO) may be used for patients if possible.

- For patients with multi-organ failure, kidney failure, continuos veno-venuos hemofiltration (CVVH) may be applied if there is designation.

- Corticosteroids may be used for cases of malignant diphtheria and laryngeal diphtheria with a lot of oedema.

- Ensuring enough nutrition: Only through vein or combination with gastrointestinal tract, depending on the patient status.

6.2.4. Hospital discharge standards and treatment monitoring

- Patients is stable after from 2 - 3 weeks of treatment.

- Staining, culturing and testing result is negative for two times and there is no complication.

- Patients must get immunization against diphtheria after hospital discharge

- To be monitored outside the hospital for 60 - 70 days in full

7. DISEASE PREVENTION

- All cases of suspicion with diphtheria must be sent to hospitals for isolation until their testing result is negative for two times.

- Each specimen is taken 24 hours apart and no later than 24 hours after antibiotic treatment. If conditions for testing are not available, patients must be isolated after 14 days of antibiotic treatment.

- To wash hands in a proper manner by soap or antiseptic solution.

- Patients’ houses, in-house tools, equipment and clothes must be disinfected and sanitized.

- Disease prevention by diphtheria vaccine: in the national expanded program on immunization, using combined vaccine: Diphtheria - Whooping cough - Tetanus for children. Immunization shall be applied when a child is 2 - 3 months old, each child shall be immunized twice, each immunization shall be taken 1 month apart with dose of 1 ml per time. Then, such child shall be immunized again once a year, until he/she is 5 years old.

- For those who in contact with infected people: To take bacteria testing and monitor for 7 days.

+ To inject 1 single dose of benzathine penicillin (for children aged ≤ 5 years: 600,000 units; for those > 5 years: 1,200,000 units).

+ Or using oral erythromycin (For children: 40 mg/kg/day, 10 mg per dose, every 6 hours) in 7 days. For adults: 1 g/day, 250 mg per dose, every 6 hours.

+ Or azithromycin: For children: 10 - 12 mg/kg, once a day with a maximum dose of 500 mg/day per day. Treat for 7 days. For adults: 500 mg/day, for 7 days.