Diphtheria

Introduction to Diphtheria Diphtheria is an acute respiratory infection caused by airborne droplets of Corynebacterium diphtheria. Diphtheria exotoxin is the main cause of disease. Its clinical features are pharyngeal, larynx, nasal and other mucosal congestion, swelling and grayish white pseudomembrane formation, as well as systemic poisoning symptoms caused by bacterial exotoxin, severe cases may have toxic myocarditis and peripheral nerve paralysis. basic knowledge The proportion of sickness: 0.0001% - 0.0002% Susceptible people: no specific population Mode of infection: droplet spread Complications: myocarditis

Diphtheria cause

(1) Causes of the disease

Corynebacterium diphtheria, referred to as diphtheria bacilli, Gram-positive bacteria, about 2 ~ 3m long, 0.5 ~ 1m wide, on the smear, often in V, X, Y arrangement, one or both ends swollen, There are concentrated granules in the bacteria, which are called meta- granules. When dyed with Neisser, the cells are yellowish brown, and the heterochromatic granules are blue-black. When stained with Albert, the cells are green and the heterochromatic particles are blue-black; stained with Ponder. When the cells are light blue, the heterochromatic particles are dark blue, and the diphtheria bacilli grow well on the potassium citrate medium, which can reduce the strontium salt and darken the colony. According to its colony morphology and biochemistry on the medium. The reaction, diphtheria bacilli can be divided into light, intermediate and heavy. In the past, it was considered that light pharyngeal diphtheria was produced, and intermediate and heavy were mostly epidemic strains, causing serious illness. At present, it is believed that type 3 bacteria can produce the same toxin, and the patient's condition There is no clear relationship between light weight and typing. In recent years, there have been reports of increased light bacteria at home and abroad. The phage lysis method, bacterial DNA restriction endonuclease method and virulence test have been used to study the isolated diphtheria bacilli. It is helpful to further understand the disease. Diphtheria bacillus has weak invasiveness and only grows in local mucosa or skin. The exotoxin produced by diphtheria is the main cause of disease. Exotoxin is a heat-labile polypeptide. Strong toxicity, the human lethal dose is 130ng/kg body weight, mainly invading the nerves, myocardium and adrenal glands. Diphtheria bacilli only infects the -phage carrying the toxin-producing gene (Tox), and has the ability to secrete exotoxin. If the disease-free strain can be changed to a toxic strain after treatment with the phage, the toxic strain is repeatedly seeded in the serum medium containing anti-Diphtheria phage phage, and the production ability can be lost to a non-toxic strain, and the bacteria are produced. The virulence is controlled by the phage gene, and the invasive ability is controlled by the bacterial gene. The virulence test is performed clinically using the guinea pig or Elek plate method. In recent years, some clinical reports have been made on the diphtheria bacillus isolated from the lesion of the diphtheria patient. It is unclear how non-virulent, non-virulent strains cause clinical symptoms. Further research is needed. Diphtheria exotoxin has two characteristics. One is highly antigenic and can stimulate people. Produce high-yield anti-toxins; second, it is very unstable. After storage, sunlight, chemical treatment or heating to 75 °C, it can reduce or completely lose its toxicity. Therefore, if it is treated with 0.3%-0.5% formaldehyde solution, After one month, the toxicity can be lost, and the antigenicity is preserved, and it becomes a toxoid. It can be used as a vaccination and preparation of anti-toxic serum. Diphtheria bacilli is more resistant to the external environment, resistant to freezing and drying. Toys, clothing can exist for several days, causing indirect transmission, sensitive to damp heat and chemical disinfectants, 0.1% liters of mercury and 5% phenol solution for 1min can kill the bacteria, heating at 58 ° C for 10 minutes can die.

(two) pathogenesis

Diphtheria bacillus has weak invasiveness. After invading the upper respiratory tract mucosa, it only multiplies in the epithelial cells of the epithelium, generally does not cause bacteremia. When the local mucosa is damaged, such as measles, scarlet fever, pertussis or upper respiratory tract infection, diphtheria bacilli Invasiveness is enhanced. Exotoxin produced during the breeding process of diphtheria bacilli can not only cause local lesions, but also cause systemic toxic lesions. It is the main cause of disease. The toxin has two subunits, A and B. The B subunit has no direct toxicity through a disulfide bond, but it has a receptor binding region and a translocation region, and the B subunit can interact with a cell surface specific receptor (membrane receptor pro-hHB-EGF). Binding, by binding through the translocation region, can transport the A subunit into the host cytoplasm.

The A subunit is toxic and can inactivate the cell elongation factor-2 (EF-2), which is an essential enzyme for the peptide chain synthesis translocation reaction, and the ribosome is inactivated. The peptide chain being synthesized on the "receipt" cannot be translocated to the ribosome "give", so that the aminoacyl-tRNA cannot bind to the ribosome, the peptide chain extension reaction stops, and the target cell dies due to the inability to synthesize the protein, thus the diphtheria toxin It has direct lethal effect on mammalian cells. The bacteria cause local tissue mucosal epithelial cell necrosis, vasodilation, massive fibrin exudation and leukocyte infiltration. The strong toxic effect of exotoxin on cells is more serious local inflammation, necrosis, mass Exuded fibrin and necrotic cells and white blood cells, bacteria and other coagulation to cover the surface of the damaged mucosa to form a special lesion of the disease, that is, pseudomembrane, the pseudomembrane is generally grayish white, may be yellow or dirty when mixed infection, When it is accompanied by bleeding, it can be black, it starts to be thin, then it becomes thicker, the edge is neat, it is not easy to fall off, the bleeding point can be seen when peeling off forcefully, the pseudomembrane formation and surrounding tissue are mild Congestion and swelling, the laryngeal, tracheal and bronchial coating of the columnar epithelium formed by the pseudomembrane and mucous membrane adhesion is not tight, easy to fall off causing asphyxia, exotoxin is locally absorbed, causing systemic toxemia symptoms, toxin absorption can be due to the pseudomembrane site and The range is different, the pharyngeal toxin absorption is the largest, the tonsils are the second, the throat and trachea are less, the more common the pseudomembrane, the larger the toxin absorption, the heavier the disease, and the toxin is also adsorbed on the cell surface. Neutralization, if it has entered human cells, can not be neutralized by anti-toxins, so clinically emphasize the early application of antitoxins in sufficient quantities. Exotoxin can cause systemic pathological changes after binding to various tissue cells, including myocardial and peripheral nerves. The heart often enlarges early, the heart muscle often has turbid swelling and fatty degeneration. Later, there may be multiple focal glassy changes, myocardial necrosis and mononuclear cell infiltration, and the conduction beam can also be involved. Finally, there may be connective tissue hyperplasia, occasionally Intracardiac thrombosis, neuropathy is more common in peripheral nerves, myelin is often fatty degeneration, nerve axis is also broken, sensory nerves and motor nerves can be Tired, but mainly for motor nerves, the ninth and tenth brain nerves are most susceptible, and the damaged nerves are rarely necrotic, so diphtheria paralysis can be almost restored, the kidneys may be turbid and swollen and the renal tubular epithelial cells fall off, the adrenal glands may have Congestive: degenerative changes or hemorrhage, hepatocytes can be fatty degeneration, and hepatic lobules can have central necrosis.

Diphtheria prevention

Comprehensive measures based on vaccination should be adopted.

1. Control the isolation of infectious sources, treat patients until the symptoms disappeared 2 times negative nasopharyngeal culture, if there is no culture condition, in the case of adequate treatment, can be isolated at 2 weeks of the disease, should be nasal for close contacts Pharyngeal culture and observation for 7 days, for children who have not received full immunization, it is best to inject the purified diphtheria toxoid and antitoxin at the same time. During the epidemic, the nursery school and the primary school should carefully carry out the morning check, actively treat the carriers, and use penicillin for common use. Dosage treatment for 5 to 7 days, contact in groups of children and adults should be observed for 7 days, and nasopharyngeal swab culture and diphtheria toxin test, adults should also make these tests for close contacts:

1 culture and toxin test are positive as diphtheria case treatment, should be isolated and treated with penicillin, once the symptoms appear, use anti-toxin.

2 culture positive, positive toxin test were treated as diphtheria cases.

3 Those who are negative in culture and toxin test can be released.

4 culture negative, toxin test positive, should be given vaccination.

2. Improve immunity of the body immunity: use white, hundred, broken mixed vaccine or adsorption purified diphtheria toxoid injection, passive immunization: diphtheria susceptible patients can not accept diphtheria toxoid injection due to weakness or illness and contact with diphtheria Patients, can give antitoxin, adult 1000 ~ 20000U intramuscular injection, children 1000U, effective only 2 to 3 weeks, the body's immunity to diphtheria, determined by the blood anti-toxin level, serum contains 10U / L is protective, can Using the diphtheria toxin (Sikh) test, or indirect hemagglutination test and ELISA to detect anti-toxin levels in the serum of the population, to understand the anti-toxin level of the population, to help predict the possibility and extent of the diphtheria epidemic, and to detect the effect of vaccination, The level of immunization in the population is negatively correlated with the incidence rate. The antitoxin level in some areas of China has reached 85% to 95%. There is no diphtheria epidemic in these areas in the near future.

Diphtheria complications Complications

Although diphtheria toxin can affect whole body cells, the heart, nervous system and kidney are most prominent. Severe diphtheria can be complicated by myocarditis or peripheral nerve palsy, and occasionally toxic nephritis can occur.

(a) cardiovascular system

1. Peripheral circulatory failure manifests as nausea, vomiting, pale complexion, cold limbs, weak pulse, decreased blood pressure, etc. If myocardial damage occurs at the same time, the symptoms of circulatory failure may be aggravated.

2. Toxic myocarditis is the most common disease, the most common complication occurs in the second to third weeks of the disease, but also occurs in the first week and the sixth week. In general, the more the toxemia Heavy, myocarditis occurs earlier and heavier, some patients with severe symptoms after treatment, the pseudomembrane shedding, but still can occur myocarditis, manifested as often weak, weak, pale, irritability, arrhythmia, atrioventricular block The first heart sound is low and blunt, the heart is enlarged, the liver is swollen, the urine volume is reduced and there is edema, and the electrocardiogram is abnormal.

(B). Peripheral nerve palsy with motor nerve damage is more common, soft palsy is the most common, into the fluid diet cough, sag reflexes disappear, mostly occurred in the third to fourth week of the disease, the severity of the disease appeared early, followed by If the eye muscles are paralyzed, if the oculomotor nerve is damaged, the eyelids may sag and the near things may not be seen. The paralysis of the nerves may cause esotropia or facial paralysis. In addition, flaccid paralysis may occur in the whole body muscles, such as the neck. Muscle, chest muscles, intercostal muscles, limb muscles, leading to the corresponding movement disorders, in the 7th to 8th week of the disease, occasionally symptoms of vagus nerve paralysis, increased heart rate, sweating, increased secretions, decreased bowel movements, diphtheria The paralysis caused can basically recover without leaving sequelae, and it will recover within weeks to months. Some people may have symptoms of sensory nerve damage, such as abnormal feeling, hypersensitivity, etc., but it is rare.

(3) Bronchial pneumonia is more common in young children. It is often secondary infection. Patients with pharyngeal diphtheria, especially when the pseudomembrane extends down to the trachea and bronchi, are more conducive to the occurrence of pneumonia. After the tracheotomy, if the care is not strict, it is very It is easy to happen.

(D). Toxic nephropathy, diphtheria patients appear in the urine protein, red blood cells and casts are more common, but true acute nephritis is rare, a small number of critically ill patients may have uremia, poor prognosis.

(5) Secondary infections of other bacteria may be complicated by acute pharyngitis, suppurative otitis media, lymphadenitis, sepsis, etc.

Diphtheria symptoms Common symptoms Skin diphtheria diphtheria pseudomembrane formation on the tonsils with gray membrane tonsil congestion, cough, fever, nausea, stuffy nose, restlessness, restlessness

The incubation period is 1 to 7 days, usually 2 to 4 days. According to the lesion, it can be divided into pharyngeal diphtheria, throat diphtheria, nasal diphtheria and other parts of diphtheria. Adults and older children are mostly pharyngeal and diphtheria. Other types of diphtheria are more common in Young children.

1. Pharyngeal diphtheria is the most common, accounting for about 80% of the number of cases, according to the extent of the lesion and the severity of the symptoms can be divided into:

(1) pharyngeal diphtheria without pseudomembrane: more common in diphtheria epidemics, some patients may only have upper respiratory symptoms, such as sore throat, systemic poisoning symptoms are mild, no fever or mild fever, only mild inflammation in the throat. The tonsils can be swollen, but there is no pseudomembrane formation, or only a small amount of fibrinous exudate, bacterial culture positive, such patients are easily misdiagnosed and missed diagnosis.

(2) Limited pharyngeal diphtheria:

1 tonsil diphtheria: the pseudomembrane is confined to one side or bilateral tonsils,

2 pharyngeal diphtheria: the pseudomembrane is confined to the zygomatic arch, sag (hanging sag), etc., more common in adults and older children with partial immunity, slow onset, may have mild heat, or moderate fever, The patient has general malaise, fatigue, loss of appetite and other systemic symptoms. At the same time, sore throat, tonsil congestion, local swelling, pseudomembrane in a punctate or small piece, enlarged into a piece within 1 to 2 days, the pseudomembrane is grayish white, border Clear, not easy to peel off, if forced stripping can cause basal facial bleeding, the submandibular lymph nodes often can be swollen, slightly painful, but the surrounding tissue is edema.

(3) disseminated pharyngeal diphtheria: patients with localized disease, if not treated promptly and effectively, the pseudomembrane can spread to the sag, soft palate, posterior pharyngeal wall, nasopharynx and throat, even to the oral mucosa and become disseminated Type, this type is more common in young children, the fake membrane is large and thick, it can be grayish white, it can also be yellow, dirty gray or black, the mucous membrane around the pseudomembrane is red and swollen, the tonsils are swollen, the submandibular lymph nodes and cervical lymph nodes are swollen. Large, tenderness, edema around the lymph nodes, this type of patients with obvious symptoms of systemic poisoning, patients can be high fever 40 ° C, dizziness, headache, weakness, nausea, vomiting, and then circulatory failure, patients pale, pulse speed .

(4) poisoned pharyngeal diphtheria: this type can be converted from restricted type and disseminated type, or it can be primary, mixed infection, especially streptococcal infection, wide range of pseudomembrane, mostly black due to bleeding The tonsils and pharynx are highly swollen, the pharyngeal door can be blocked, or there is necrosis, ulceration, special rancid smell, neck lymph nodes, edema around the tissue, causing swelling of the neck or even the tissue near the collarbone. "Necken", patients with high fever, irritability, shortness of breath, pale, lip blemishes, thin and fast pulse, blood pressure drop, and some may appear heart enlargement, arrhythmia such as galloping, etc., if not treated in time, more Death within 2 weeks.

2. Throat, diphtheria, diphtheria and diphtheria are found in about 20% of patients, of which 1/4 are primary, the patient has no lesions in the pharynx, 3/4 is the pharyngeal diphtheria, and the primary pharyngeal diphtheria is more common in 1-3. The young child, who is a "canine" cough, hoarseness or even loss of voice, due to the presence of a pseudomembrane in the throat, trachea, etc., causes varying degrees of difficulty in breathing, mainly manifested as inspiratory dyspnea, if the pseudomembrane is extended Trachea, bronchus, dyspnea is more serious. If the tracheal intubation is not performed in time for tracheal intubation or tracheotomy, the patient often dies within a day or two, because the laryngeal and tracheal pseudomembrane and mucous membrane adhesion are not very strong, sometimes It can cough up or suck out the tubular pseudomembrane, so the difficulty of breathing can be alleviated. Because the toxin is absorbed less, the symptoms of systemic poisoning are not serious.

3. Nasal diphtheria is rare in this type. It is more common in infants and young children. It is mainly characterized by nasal congestion, bleeding, serous secretions, and prolonged unhealed. The periorbital and upper lip of the nostrils often cause superficial ulcers due to the erosion of secretions., simple nasal vestibular diphtheria, pseudomembrane can be located on one side or both sides, children without heat or slightly hot, often have breast-feeding disorders, mouth breathing, restless sleep, weight loss, etc., secondary to more from pharyngeal diphtheria.

4. Other parts of diphtheria diphtheria can invade the eye-binding membrane, ear, girl genital area, neonatal umbilical and skin lesions, pseudomembranous and purulent secretions appear in different parts, eyes, ears and genital diphtheria are mostly Secondary, skin diphtheria is common after skin wounds, often accompanied by mixed infection, pseudomembrane is yellow or gray, necrosis and ulceration can form, nearby lymph nodes can be swollen, skin lesions often do not heal, after healing, there may be melanin Calm, patients rarely have symptoms of systemic poisoning, but peripheral nerve palsy can occur, the incidence of skin diphtheria is not high, but the incidence of skin and diphtheria in some areas is significantly increased, more common in the tropics.

Diphtheria examination

1. Bloody leukocytosis, generally (10 ~ 20) × 109 / L, the proportion of neutrophils increased, severe cases may appear poisoning particles.

2. Bacteriological examination at the junction of the pseudomembrane and the mucosa, smear examination and culture (Lu's medium), often can find Gram-positive bacilli or diphtheria bacilli, if necessary, can be used for virulence test of diphtheria, test method More, guinea pig intradermal injection method: take two guinea pigs, one of them was injected with 250 U antitoxin before the test, then both guinea pigs were injected intradermally with 0.1 ml of the test solution (cultured in Lu's medium for 18-24 hours) The bacterial liquid washed with 5ml of broth), after 24 to 72 hours, if the injection site of the anti-toxin-injected animal is red and swollen, and the injection does not change, it proves that the test strain is toxic.

3. Serological examination using fluorescent antibody method, detection of diphtheria bacilli under fluorescence microscope, can be diagnosed early.

4. Rapid diagnosis of potassium citrate.

5. Other examinations of ECG can help to detect toxic myocarditis, urea nitrogen, creatinine, liver function changes in liver and kidney damage.

6. Toxic myocarditis ECG shows that the PR interval prolongs ST-T wave changes.

Diphtheria diagnosis

diagnosis

Special emphasis should be placed on early diagnosis, which is not only beneficial for prevention, but also directly related to the prognosis of the patient. The earlier the treatment, the better the prognosis.

1. Epidemiological data should be aware of the local diphtheria prevalence, vaccination, whether adequate vaccination has been received, whether there are diphtheria patients around, whether it is the epidemic season.

2. Clinical features: fever, sore throat, hoarseness, nose, pharynx, and throat. It is not easy to exfoliate. Forcibly exfoliating and bleeding should consider this disease. Pharyngeal diphtheria is the most common. Strong dry cough is the most common symptom of pharyngeal diphtheria. Infants and young children may have nasal diphtheria, ulcers that have been cured for a long time, and the possibility of diphtheria should be considered.

3. Bacteriological examination smears can be stained with Neisser or Ponder. Any typical clinical manifestations, and Gram-positive coryneform bacteria, and heterochromatic granules can be diagnosed clinically, but the clinical manifestations are typical but no bacteria can be found. The clinical is very atypical, but the bacteria are found and should be regarded as suspicious cases. If the culture is positive for diphtheria, the virulence test is positive, then the diagnosis can be confirmed.

Differential diagnosis

(1) pharyngeal diphtheria needs to be identified with the following diseases

1. Acute tonsillitis has an acute onset, high fever, tonsil swelling, sore throat; thin secretions, light color, limited to tonsils, easy to peel off.

2. Thrush is not hot, white lumps are attached to the oral mucosa, can spread to the pharynx, white film is loose, easy to peel off, although the lesion range can be very wide, but the symptoms of poisoning are not significant.

3. Ulcer membranous pharyngitis There are necrotizing ulcers and pseudomembranes in the pharynx, often accompanied by gingivitis, bleeding, oral malodor, throat swab smear can find Fusobacterium and spirochetes.

4. Infectious mononucleosis There is a white membrane on the tonsils, slow regression, smear and culture without diphtheria, diphtheria antitoxin treatment is ineffective, abnormal lymphocytes in the surrounding blood, blood heterophilic agglutination test can be positive, specific resistance All positive.

(2) Throat and diphtheria need to be differentiated from the following diseases

1. Acute laryngitis in children with acute laryngeal obstruction mostly due to acute laryngitis, measles complicated by laryngitis and laryngeal diphtheria, measles and laryngitis have a history of measles; acute laryngitis onset, sudden breathing difficulties, due to the primary Patients with laryngitis have no pseudomembrane in the pharynx, so it is difficult to confirm when there is laryngeal obstruction; if there is a white film ejected from the tracheal incision, the diagnosis of diphtheria should be considered.

2. There is a history of foreign body inhalation in the trachea. When the foreign body inhales, there is a severe cough. After the cough is paroxysmal, no pseudomembrane is found. Local emphysema or atelectasis is often seen in the chest.

(3) Nasal diphtheria needs to be differentiated from the following diseases

1. The foreign body in the nasal cavity is often one-sided. When examined, foreign bodies in the nasal cavity can be found without a pseudomembrane.

2. Congenital syphilis is often accompanied by other symptoms of syphilis, ulcers in the nasal cavity without white membrane, and serum Huakang reaction is positive.

3. Chronic rhinitis

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