DIPHTHERIA

DIPHTHERIA

http://www.medicinenet.com/diphtheria/article.htm

 Diphtheria is an acute infectious disease caused by Leffler bacilli, transmitted mainly in an air-drop way and characterized by the symptoms of general intoxication, local inflammation of the mucous membranes mainly with the formation of fibrinogenous fur and typical complications on the part of the nervous system, cardiovascular system and excretory system.

Klebs discovered the diphtheria pathogen Corynebacterium diphtherias in the sections of diphtheria membranes in 1883. In 1884 Leffler extracted it in clean culture and infected a number of animals, among which Guinea pigs turned out to be responsive to the infection.

Etiology

The distinctive qualities of the diphtheria microbes are their  polymorphism. Gram-positive coloring and the typical location of rods in the form of “bristling fingers” or V-figures. The diphtheria microbes are immobile, they don’t produce spores, and do not have capsules or flagellums. They are usually situated one by one, however, in the diphtheric membranes and clean cultures they are often found in the form of assemblage resembling a constitution of felt.

On the Lefler medium the diphtheria microbes yield the best growth (colonies) during 16-20 hours; the growth can be observed even in 6-8-10 hours after sowing.

Epidemiology

http://bestpractice.bmj.com/best-practice/monograph/738/basics/epidemiology.html

The source of diphtheria is a person in whom it is manifested in various clinical forms – from serious toxic forms up to the deleted ones and healthy bacteria-carrying. There are infrequent reports on people being infected with diphtheria from animals.

The duration of the microbe vegetation in the organism and the terms of purification mostly stipulate the epidemic danger of the bacteria-carrier as a source of infection. In practice it is difficult to determine the true duration of bacteria discharge because of the absence of precise information about its beginning.

The most epidemically dangerous are the bacteria-carriers who discharge microbes for a long time (up to 1 month and longer), it is more often observed in patients with chronic diseases of the upper respiratory tracts particularly with tonsillitis.

It is known that the diphtheria infection is transmitted in an airdrop way, which is inherent for the majority of respiratory infections. Nevertheless it is necessary to briefly mention some aspects of the transmission mechanism, particularly the pathogen survival rate in the environment. Various enviromental factors can influence the transmission of the diphtheria infection, however, they play a small role and more often have casuistic nature. The leading role in the epidemiology of diphtheria belongs to the drop mechanism of the transmission.

Pathogenesis

The diphtheria infection develops only in case of the parenteral entering of poison into the organism.

Implanting in the organism through covering tissues the diphtheria pathogens form local foci of histic damage. More often it happens on the mucous membranes of the stomatopharynx, nasal-courses where the microbes utilize slime as a medium, less often the foci develop on the skin and even less often on the mucous membranes of an eye and vulva-vaginal area. Alongside with classic exotoxin, which is a true lethal factor, the diphtheria microbes in the zone of inoculation produce numerous solvable local-acting factors (hyaluronidase and neuraminidase) damaging the cells and facilitating the diffusion of bacteria and toxins in the tissues.

The local cytopathogenic effect of the toxin is determined by the rate of the poison entering the tissues, by the toxin-aggregating capacity of the cells and the availability of the microbial spreading factors (neuraminidase, hyaluronidase). If poison enters slowly, there appear conditions for the manifestation of its local cytotoxic action in the area of inoculation, but if the toxin concentration in this area increases rapidly, then in a short time the “threshold” dose is accumulated, and in case of its exceeding the poison is reabsorbed in the circulation system and already has a predominantly systemic pathogenic effect.

Pathologic anatomy

Fibrinous inflammation is the pathomorphologic manifestation of the  macro- and microorganism interaction in diphtheria. The form of this inflammation directly relates to the constitution of the affected mucous membrane. If the process develops on the mucous membrane covered with the single-layer cylindrical epithelium (for example in the respiratory tracts), croupous inflammation develops; the cover that develops includes a necrotic  epithelial layer. The cover is not firmly connected with the underlying tissue and can be easily separated from it. If the process develops on the mucous membranes covered with a multilayer flat epithelium (lumen of fauces, pharynx), it is not only the epithelial layer that necropsies, but partially the joint tissue basis of the mucous membrane (tunica propria mucosae). A thick fibrinous cover develops, it can be hardly removed from the underlying tissues. It is diphtheria inflammation.

The regional lymph nodes get involved in the process: they are enlarged owing to the expressed plethora, edema and the proliferation of the cell-like predominantly reticuloendothelial elements. Local necroses develop in them. In the toxic form of diphtheria develops the edema of the fauces mucous membrane, pharynx, and also the edema of cervical fat in the immediate proximity of the affected regional lymph nodes. In the basis of this edema there is a serous inflammation in the form of numerous cell-like infiltrates.

The diphtheria intoxication is characterized by the affection of the nervous system (mainly the peripheral nerves of the sympathetic ganglions), cardio-vascular system, paranephroses and nephroses.

The changes of the peripheral nerves are manifested by multiple toxic parenchymatous neuritis, in diphtheric polyneuritis the process can spread on the intraganglion fibers of intervertebral nodes and their cranial homologues.

The cardiovascular system is considerably affected in the diphtheria intoxication. The vessels affection is mainly manifested in their paretic dilatation with the symptoms of stagnation which can transform into stasis. The deep degenerative changes are observed on the part of myocardium. The changes of myocardium in the hearts of children who died on the 3-5-th day  of the third degree toxic diphtheria or hemorrhagic diphtheria were manifested only in expressed plethora, an edema of the intermuscular tissue with frequent hemorrhages: the fibrinous degeneration of the vessels walls was constantly observed.

Clinical manifestations

http://www.tcmwell.com/TCMDiseases/Otorhinolaryngology/The-clinical-manifestations-of-diphtheria.html

The incubation period, as in the other forms of diphtheria, lasts from 3 to 10 days. The disease has either an acute, sudden, or step-by-step oncoming with hardly noticeable symptoms, in the first case the temperature immediately rises up to 38-39 °C, there is a headache, malaise. In the second case a child develops poor appetite, flaccidity, slight temperature rise (37.5-38 °C) during several days. Quite often even senior children do not complain of a sore throat or the pain is insignificant, and if the doctor is not in the habit of examining a throat in each patient with a fever, diphtheria in such cases is not revealed by the parents and the doctor as well. If the patient is examined during the first day of the disease it is possible to notice a slight pulse acceleration, which correlates with the temperature; the cervical glands are usually slightly enlarged on one side, painful at pressing. The tongue is furred, the tonsils are swollen either both or mostly, one of them, turn red, but the erythema is strictly localized and does not spread on the uvula and soft palate as in scarlet fever. It is possible to discover fur on the reddened tonsil, during the first hours of the disease it looks like a mild combustion of the mucous membrane or a heavy-bodied web grid; it is possible even to remove it by a cotton plug but a new one appears on its place extremely fast, and it cannot be removed any more. By the end of the first day or by the beginning of the second day the fur gets a characteristic diphtheria cover properties: it is dirty-gray or yellowish, rather thick, rises above the mucous membrane surface, it cannot be removed without bleeding; plenty of fibrin and diphtheria bacilli can be discovered under the microscope in it. The manifestations of the general intoxication remain insignificant: a headache, malaise, poor appetite. The borders of the heart are normal and the tones are clean. The pulse is accelerated; the blood pressure is in  the normal range or slightly heightened. The liver and spleen are not changed; the urine does not contain protein. There is moderate leukocytosis (10.000-12.000) and neuthrophylia in the blood. The following course of the disease can be diverse. Nowadays, when the serum treatment is widely applied, the natural course of diphtheria can be observed very seldom. Therefore, it is necessary to distinguish the diphtheria course during serum treatment and without it.

The diphtheric affection of the larynx and respiratory tracts is known under the name of a croup.

Croup (true, diphtheric) can be secondary, if it develops after the affection of the fauces or the nose, and primary – at the primary localization of the diphtheria process in the larynx.

The course of croup can be divided into three stages.

1. A croup cough stage. The first symptom indicating the starting affection of the larynxes is sharp loud cough, which becomes rasping, barking very soon. Senior children complain of the sense of smart and pressure in the larynx; the palpation of the larynx appears to be painful. At the same time the voice becomes hoarse, unclean, and then completely silent (aphonia). At the examination with a laryngeal mirror it is often possible to see an edema and hyperemia of the epiglottis, and often there are no covers at this stage. This period lasts 1-2-3 days and develops into a second stage.

2. A stenosis stage. The respiration becomes labored, unclean; at each inspiration the sawing or whistling sound is audible. This sound is weak at the beginning and audible only during exaltation and the child’s cry, then it becomes sharp, constant and is audible from the distance. Another symptom is the larynx narrowing — retraction of compliant, weaker places of the thoraces. As the insufficient amount of air enters the lungs through the narrowed glottis, the intrapulmonic pressure becomes lower than the atmospheric one and under its influence- the compliant places of the thoraces — the supraclavicular and bulbar-fossas; intercostal spaces, anticardium – are more or less sharply retracted at each inhalation. At first a child is quiet, satisfactorily manages the air deficiency. Then the oxygen deficiency develops – the child becomes restless, rushes in bed, jumps up, grasps the handles of the bed, wants to be held in his mother’s arms, showers his head to the back. The auxiliary muscles start to work – intercostal, mm. sterno-cleido-mastoidei, mm. scaleni. The sterno-clavicular muscle appears to be noticeably tight at the palpation during an inhalation. When the child is in such a condition, injecting the serum and  providing the adequate treatment (an operation and other treatment measures; (see Treatment of croup below) can save him. If the disease has its natural course, the condition improves and the stenosis easies in the extremely infrequent cases when the cover disappears; in most cases the disease reaches its last stage.

3. An asphyxia stage. In the struggle with stenosis the child exhausts, the respiratory muscles get tired. The child becomes calm, sleepy, he inditfferently lies in bed. The respiration is accelerated, but it is superficial, the retractions are already not so visible. The lips, tip of the nose and nails become blue, the face turns pale, sweat quite often appears on the forehead. The extremities are cold, the pulse is very rapid, thready, sometimes paradoxical (abasement of the pulse wave during the inhalation). From time to time there are attacks of acute dyspnea – the child jumps up, rushes because of air-deficiency, the eyes express fright, the face becomes cyanotic; sometimes such attacks result in the immediate death; in other cases the child dies after a more or less continuous agony with the symptoms of exhaustion of respiratory and circulation centers.

Complications

The most frequent diphtheria complication for adults is myocarditis. The affection of the heart is especially typical for the toxic forms of the disease.

The severe form of myocarditis develops only in the patients with toxic diphtheria (except subtoxic) at overdue (after the 5th day of the disease) specific treatment and is always accompanied by complications on the side of the kidneys and nervous system.

The complications caused by the affection of the nervous system are observed less frequently. In the mild forms of diphtheria (localized, wide-spread) the adults develop only the soft palate paresis — mononeuritis, which has an easy short-term course (no more than 10-14 days), characterized by a snuffling voice and chokes while eating liquid food. In more than 1/3 cases toxic diphtheria is complicated by polyneuritis in various combinations and polyradiculoneuritis. Among the cranial nerves the IX, X, III, VII, XII pairs are affected more often, it results in paresis or paralyses of the soft palate, pharynx, tongue, accommodation paresis and mimicry affection.

 The severe forms of polyradiculoneuritis develop only in patients with concomitant alcoholism, they are characterized by deep wide-spread paralyses of the extremities, body, neck, respiratory muscles in combination with the affection of the cranial nerves, resulting not only in the long-lived disorders of the working capacity, but also in lethal outcomes, even in subtoxic diphtheria.

One or two-sided focal pneumonia quite often develops at the early stage of the disease in toxic diphtheria.

Diagnosis

The modern microbiologic diagnosis of diphtheria is based on the clean culture isolation and identification of the pathogen by the cultural-morphological, biochemical and toxicogenic properties. Thus, it is necessary to strictly observe a number of conditions. The slime from the stomatopharynx and nose as well as the secret from other areas of the pathological process localization are collected by separate wads before eating or after it but not earlier than in 2 hours, and also before gargling and other kinds of treatment (drops, ointments, wads).

Taking the material for research correctly is of great importance. In the stomatopharynx slime is taken from the tonsils, palatal aerofoils, uvula and trailing wall of the pharynx by rotary movements of a wad obligatory with the help of a glass spreading rod, not touching the mucous membrane of the cheeks and tongue. If there is fur of fibrinous nature, the material should be taken both from the affected tissues and the healthy tissues adjacent to them. A small part of the removed coat, which is carefully ground between glasses, or a smear taken by a separate wad are sent to the laboratory for the direct bacterioscopic investigation. The scooping of the material from the nose should be done after the careful preliminary purification of it from the slime by a dry cotton plug or after blowing the nose.

Though the streamlining of some stages of the bacteriological research accelerates the terms of carrying out an analysis to some extent, they all remain rather prolonged and do not guarantee the early diagnostics of diphtheria.

Serological, immune-chemical and the immunological methods play a more and more relevant role in the diagnostics and epidemiological evaluation of the disease. On their basis are designed the accelerated methods of discovering diphtheria toxin in clean and blended cultures in case of growing them in liquid mediums and other substrates.

The serological tests are applied to study collective immunodeficiency. RDGA is the most accessible, simple and quite informative.

 Treatment

http://www.mayoclinic.com/health/diphtheria/DS00495/DSECTION=treatments-and-drugs

 Hospitalization of patients is obligatory. In case of a  toxic diphtheria  patients transport only laying. The severe confinement bed regime is necessary during 20-25 days, then at absence of complications the patient allow to sit and gradually dilate impellent regime. At mild forms (localized diphtheria of pharynx,  diphtheria of nose) duration of confinement bed regime is reduced up to 5-7 days. In the acute period of disease fluid and semifluid nutrition is necessary. Treatment may be specific and pathogenic.

Specific treatment will carry out by high purified horse hyper immune serum. For prevention of anaphylactic reactions infuse serum behind by Bezredko method. First of all 0,1 mL diluted 1 : 100 of serum infuse intracutaneous of forearm. If after 20-30 min. on a place of injection there are not changes or the papule in diameter is not more than 0,9 sm, – reaction is negative, and infuse 1 mL undiluted Serum sub dermal, and at absence of reaction – after 30 min all prescript dose in muscle.

At toxic diphtheria II-III stage and the hyper toxic form a serotherapy is carried out necessarily, under protection of hormonal preparations, and sometimes – narcosis. In case of positive intradermal assay or at presence of anaphylactic reactions further subdermal infusion of serum only behind unconditional indications. Serum in dilution 1: 100 is infused in a sub dermal fat of brachium in doses 0,5; 2; 5 mL consecutive with intervals 20 min. At absence of reaction to previous dose infuse 0,1 mL undiluted serum subcutaneously. If reaction is not present, through 30 min infuse all prescribed dose subcutaneously. In unusual cases serum is infused under narcosis.

Antitoxic serum neutralizes only a toxin, which circulates in a blood, and does not influence on fixed in tissues. Therefore specific treatment may be carried out as soon as possible (optimum in 1 – 3 rd day of disease).

The form of diphtheria determines doses of serum for the first introduction and course of treatment.

At late (after 2 nd day of disease) beginning of treatment of patients with the widespread or toxic form the first dose of serum should be increased. The form of disease also determines frequency rate of infusion of serum. In case of localized diphtheria of a throat, nose, rare localization of process and early serotherapy is possible to be limited by disposable infusion of serum. If diphtheria of throat is widespread, infuse Serum during 2-3 days (at the toxic form – through every 12 hours). The first dose makes 1/3 – 1/2 course; in first two days patient may receive ¾ of course doses.

In case of diphtheritic croup the initial dose of Serum is determined by it’s stages – 15-20 thousand AUN, II stage – 30-40 thousand AUN ,  at III stage- 40 thousand AUN, through 24 hours this dose repeat, and the following one of these days if it is necessary, infuse half dose of Serum.

Usually the course of serotherapy lasts no more than 3-4 days. Indications for stopping of serotherapy are disappearance or decreasing of spot, edema of pharynx and hypodermic fat of the neck, at croup – complete disappearance or decrease of stenotic respiration. At suspicion on toxic diphtheria serum should be infused immediately; at localized form – it’s possible waiting the reception of results of bacterioscopy, otolaryngology’s-review etc., but under condition of constant surveillance in hospital; on diphtheritic croup – infusion of serum is obligatory if this diagnosis is not refused after carrying out of intensive cure during 1-1,5 hours.

For intensifying action of Serum intramuscularly recommended infusion once a day 25 % of a solution of magnesium sulfates right after beginning of serotherapy.

Pathogenetic treatment is directed on desintoxication, restoration of hemodynamic and elimination of adrenal gland insufficiency. Desintoxication therapy provides intravenous infusion of 10 % solution of glucose with insulin, albuminous preparations and colloid solutions in the ratio 1:1. A liquid is infused at the rate of 20-30 mL/kg of mass. Diuretic agents, are indicated under the control of arterial pressure and diuresis.

For improvement of tissue metabolisms cocarboxylase, acidum ascorbinicum, a nicotinic acid, ATP are indicated. The nicotinic acid decreases also an influence of diphtheritic toxin, and ascorbic – stimulates imunogenesis and function of cortex of the adrenal glands.

Prednisolonum (2-3 mg/kg) or Hidrocortizonum (5-10 mg/kg per day) are prescribed to the patient with widespread and toxic forms of diphtheria with the purpose of replaceable, anti-inflammatory and hyposensibilisative treatment for 5-6 days. In the first 2-3 days Glucocorticoides are infused in vein, then per os. In case of hypertoxic and hemoragic forms the daily dose of Prednisolonum is enlarged up to 5-20 mg/kg according to stage of shock.

At toxic form of diphteria, since the first day there is indicated 0,1 % solution of Strychninum of Sodium nitritum (0,5-1,5 mL subcutaneously) during 2-3 weeks and more. Strychninum stimulates tone of the central nervous system, stimulates respiratory and vasomotor centers, tones up sceletal muscles and a myocardium, stimulates oxidant-recreated processes in myocardium. Use of Cordiaminum, Corazolum raise a tone of organs of circulation. At cases of DIC for desagrigation, except Reopolyglucini, indicate antihistamines, vasodilators, Trentalum, Ksantinoli. For reception of anticoagulative effect infuse Heparini (150-400 UN/kg  per day). Inhibitors of proteases are recommended.

Antibacterial therapy is prescribed with the purpose to impact on Corynebacterias diphtherias and secondary flora. It is expedient to apply Benzylpenicilini, Tetracyclinums, Cefalosporines, Erythromicini.

Treatment of patients with diphtheria of larynx. Patogenic treatment is indicated: Sibazonum (Seduxenum) and etc. Oxygen therapy is provided. In case of a stenosis of larynx without respiratory failure the good effect gives a warm soda drink, Sinapismuses and etc. hyposensibilisative preparations (Dimedrolum, Pipolfeni, Tavegili etc.) are used to decrease the edema of mucous, locally antiedema and anti-inflammative therapy in aerosols (inhalations) is prescribed.

Complex treatment provides also indication of Glucocorticosteroides, in particular Prednisolonum (2-3 mg/kg per day), which, except for anti-inflammatory action, assist decrease of edema of larynx, reduce a permeability of wall of capillaries and exudation. Half of daily dose is infused intravenous or in muscle, the rest is given per os. After prescriptions desintoxicative therapy will carry out. Antibiotics of wide spectrum action are prescribed. If conservative treatment is not effective, operative measures are used.

Triad of signs to be the indications to initial intubations (tracheostoma):

а) Paradoxical pulse (inspiratory asystolia of Raufus); b) sign of Baie: continuous contraction sternocleidomastoideus muscles during  inspiration; c) proof cianosis of labiums and face. In case of a localized croup – long nasotracheal intubation, at a wide-spread descending croup tracheostomy with the following drainage of trachea and bronchuses are indicated.

Treatment of complications. At myocarditis optimum duration of the bed period regime is near 3-4 weeks. There are indicated Strychninum (a long course); solution of glucose with cocarboxylase, Acidum ascorbinicum, ATP, calcium pangamatis, agents which influence on tissue metabolism (a methandrostenolone, a potassium Orotatis). At serious and medium myocarditis Prednisolonum per os and parenteraly (in a daily dose 40-60 mg) is recommended. Introduction of cardiac glicosodes is supposed only at manifests of heart insufficiency without disorders of contraction. Anticoagulants of indirect action are prescribed for prophylaxis of tromboembolitic complications (Dicumarinum, Neodicoumarin, Pelentanum).

The patient with diphtheric polyneuritis should be indicated Strychninum, vitamins of group B, glucocorticosteroides. In the recreating period an Oxazili inside during 15-20 days, massage, medical gymnastics (cautiously), diathermy, galvanization, quartz are applied.

At attributes of defeat of respiratory muscles indicate antibiotics of wide spectrum of action in the maximal doses for prophylaxis of pneumonia. Patient can be transfer on apparatus respiration in conditions of departament of reanimation after indications. Proceeding from action of diphtheritic toxin as inhibitor of acetylcholinesterase, Proserini at neurologic complications is indicated after fading acute displays of disease.

Treatment of toxygenic corinebacterias diphtherias carriers. At repeated allocation of bacteria – antibiotics of tetracycline lines, Rifampicini are recommended. After a seven-days course usually there comes sanitation. The basic attention should be payed to chronic disease of nasopharynx. Treatment begins with fortifying (Methyluracilum, Pentoxylum, Aloe, vitamins) and hyposensibilisative agents with physiotherapy (UHF, UF-radiation, ultrasound).

Duration of hospitalisation is determined by gravity of diphtheria and character of complications. If complications are not present, patients with the localized form may discharge from the hospital at 12 – 14-th day of disease, with spread form at – 20 – 25-th (bed regime – 14 days). Patients with subtoxic and toxic forms should be on bed regime 25-30 days; they may discharge at 30 – 40-th day of disease. In case of a toxic diphtheria II – III degree and serious current of disease the regime lasts 4-6 weeks and more. The obligatory condition for leaving the hospital of the patient with any form of a diphtheria is negative result of two control inoculations received with an interval of 2 days.

Prophylaxis

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1992177/

The major manifestations of diphtheria can be prevented in individual patients by immunization with formalin-inactivated toxin. Therefore, documentation of inadequate levels of antitoxin in large proportion of the adult population in North America and Western Europe has caused great concern that a toxigenic strain introduced into these populations could cause a major outbreak of disease. Serum antitoxin levels can be measured by toxieutralization tests in rabbit skin, in Vero cell culture, or by hemagglutination, with roughly equivalent results. Concentrations of 0.1 –  0.01 (international units) generally are thought to confer protection. For example, data from a recent outbreak showed that 90 % of clinical cases had antitoxin levels below 0.01 IU/mL, whereas 92 % of asymptomatic carriers had liters above 0.1 IU/mL. Following immunization, antitoxin levels decline slowly over time so that as many as 50 % of individuals over age 60 have serum liters below 0.01 IU/mL. For this reason, booster doses of toxoid should be administered at 10-year intervals, to maintain antitoxin levels in the protective range.

Recommendations from the Immunization Practices Advisory Committee, published by CDC in 1991 are as follows.

For children from 6 weeks to 7 years of age: three 0.5-mL intramuscular injections of (DPT) vaccine should be given at 4-8-week intervals, beginning at 6-8 weeks of age, followed by a fourth dose 6-12 months after the third.

For persons 7 years or more of age: 0.5 mL Td (toxoid—adult) is given twice at a 4-8-week interval, with a third dose 6-12 months later. Because the pertussis component of DPT is re­sponsible for most of its side effects, and the risk of pertussis is much less after age 6, that component of the vaccine is omitted. Moreover, because subjects over age 7 have a higher incidence of local and systemic reactions to the concentration of diphthe­ria toxoid in pediatric DPT vaccine (7-25 limit flocculation [Lf] units) and because a lower dose of toxoid has been shown to induce protective levels of antitoxin, the Td formulation of vaccine contains a maximum concentration of 2 Lf units of diph­theria toxoid. If the recommended sequence of primary immuni­zations is interrupted, normal levels of immunity can be achieved simply by administering the remaining doses without need to restart the series.

Booster immunizations: children who have completed their primary immunization before age 4 should receive a booster dose of DPT at the time of school entry. Persons above 7 years of age should receive booster immunization with Td at 10-year intervals. As a help to memory, this should be done at decade or mid-decade intervals (e.g., ages 15, 25, 35, etc., or 20, 3О, 40, etc.). Travelers to areas where diphtheria is still endemic should be particularly careful to be sure their immunization is current. Although the recommended booster dose of 1.5-2.0 Lf units will increase antitoxin levels to above 0.01 IU in 90-100 % of previously immunized individuals, some authori­ties have recommended using 5 Lf units, because antitoxin lev­els remain above 0.01 IU/mL for a longer period than with 2 Lf units.

Patients should receive toxoid immunization in the convales­cent stage of their disease because clinical infection does not always induce adequate levels of antitoxin. Close contacts whose immunization status is incomplete or unclear should promptly receive a dose of toxoid appropriate for their age, and complete the proper series of immunizations. In addition, they should receive prophylactic treatment with erythromycin or penicillin, pending the results of pretreatment cultures. Given these preventive measures, the prophylactic use of antitoxin is considered unwarranted.