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    Diptheria Prophylaxis PDF

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    Simbakutty Venkataramanan

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    EURVICP/CMDS 96 06 01 03 ENGLISH ONLY UNEDITED YEN Gy a REGIONAL OFFICE FOR EUROPE ANTIBIOTIC PROPHYLAXIS OF CONTACTS OF DIPHTHERIA CASES Drafted by WHO/EURO/CDC/USAID/BASICS SCHERFIGSVEJ 8 DK-2100 COPENHAGEN @ DENMARK TEL: (45) 39 17 1717 TELEFAX: (45) 39 17 18 18 TELEX: 15948 AND 12000 EURHFA target 5 TARGETS REDUCING COMMUNICABLE DISEASE. By the year 2000, there should be no indigenous cases of poliomyelitis, diphtheria, neonatal tetanis, meésles, ‘mumps and congenital rubelta in the Region and there should be a sustained dnd continuing reduction inthe incidence and adverse consequences of other communicable diseases, notably HIV infection. ABSTRACT |The WHO/UNICEF Strategy for’diphtheria control includes. three main recommendations: =: mass immunization; = eatly diagnosis and proper treatment of cases; = management of close contacts by the use of antibiotics. Whereas the first two recommendations have been implemented in all NIS having epidemic diphtheria, in some countries there is a controversial dis- cussion regarding the use of antibiotics for close contacts. Therefore WHO, with assistance of CDC and USAID/BASICS has drafted guidelines regard- ing the antibiotic prophylaxis of contacts of diphtheria cases based on international experience. The guidelines include reprints of publications demonstrating the success of this strategy. Keywords DIPHTHERIA - prevention & control ANTIBIOTIC PROPHYLAXIS (1) UNICEF Nis All tghts io thi document are reserved by the WHO Regional Orie fr Europe. The document may nevertheless be frely reviewed, abstracted, reproduced or translated into any other Ianguage, but not for sae or for use in conjunction, commercial purposes. Any views expressed by named authors are solely the responsibility of those authors. The Regional Office would appreciate receiving three copies of any translation World Health Organization Regional Office for Europe (WHO/EURO) Centers for Disease Control and Prevention (CDC) Basic Support for Institutionalizing Child Survival (BASICS) ANTIBIOTIC PROPHYLAXIS OF CONTACTS OF DIPHTHERIA CASES ‘The WHO/UNICEF Strategy for Diphtheria Control in the New Independent States, recommends antibiotic prophylaxis for close contacts of diphtheria cases (see Annex 1). The principle reason for this recommendation is to prevent the development of secondary cases among contacts. In addition, by eliminating carriage of the organism from close contacts, further spread within the community will be prevented. This latter benefit is likely to have most impact in'the overall control of diphtheria when there are relatively few cases, i. either carly in an epidemic or in the latter stages of achieving control through immunization campaigns. However it likely also has benefit during the height of an epidemic. Several published reports have documented the important role that persons asymptomatically infected with C. diphtheriae (carriers) have in spreading diphtheria.'* Persons who are fully immunized may carry the organism, transmitting the infection to susceptible persons. Thus antitibiodc treatment of carriers is an important aspect of diphtheria control By contrast with the WHO/UNICEF recommendation of treating all close contacts regardless of culture status, in many of the New Independent States, the current practice is to first culture all close contacts, and after receipt of the culture results, treat with antibiotics only those who are culture positive for toxigenic C. diphtheriae. ‘The following questions will be addressed by this document, (1) Is antibiotic prophylaxis effective in eliminating C. diphtheriae from infected carriers? (2) Is antibiotic prophylaxis of all close contacts more effective in preventing secondary cases among close contacts and in reducing spread of diphtheria in the community than the altemate strategy of waiting for culture results and treating only persons identified as culture positive for toxigenic C. diphtheriae? (3) Will wider use of antibiotic prophylaxis as advocated by the WHO/UNICEF strategy induce antibiotic resistance in C. diphtheriae, or (4) cause an unacceptable number of side effects among recipients? These questions will be addressed in tum, ‘and selected English language medical articles have been attached (Annex 2). ‘This document has been prepared jointly by the World Health Organization Regional Office for Europe, the U.S. Centers for Disease Control and Prevention (CDC), and BASICS," in order to address some concems that have been raised by public health policy makers, epidemiologists, and clinicians in the New Independent States about the recommendations for antibiotic prophylaxis of contacts of cases included in the WHO/UNICEF strategy. 1. Is antibiotic prophylaxis effective in eliminating C. diphtheriae from infected carriers? From the medical literature it is clear that both penicillin and erythromycin are highly effective, although not 100% effective, in eliminating C. diphtheriae from the nose and throat of respiratory carriers. Zalma and colleagues® during an epidemic in Austin, Texas from 1967 to 1969, treated 142 carriers with a seven to ten day course of intramuscular procaine penicillin, administering a dose of 600,000 to 2,000,000 units per day deperiding on the age of the treated person. One hundred twenty eight (90.1%) became culture negative. Those who remained culture positive after penicillin were treated with erythromycin for 7 days, with successful eradication of the organism in all cases. In an outbreak in San Antonio, Texas, in. 1970,* households were randomly assigned to be treated with either (i) benzathine penicillin (a single intramuscular dose of 600,000 units for age 1-5 years and 1,200,000 units for age 5 years), (ii) erythromycin estolate by mouth for 7 days, or (iii) clindamycin by mouth for 7 days. The carrier state was terminated in 125 (89%) of 149 carriers treated with penicillin, 82 (92%) of 89 weated with erythromycin, and 52 (93%) of 56 treated with clindamycin, Although there is a trend towards apparent greater efficacy of erythromycin compared to penicillin, this difference fails to meet statistical significance.” Almost all patients were culture negative within 4 days of beginning antibiotics. ‘The findings of these two reports may be compared to studies conducted during the pre- antibiotic era which analyzed the rate of disappearance of C. diphtheriae from the nose and "BASICS (Basie Support for Instiutionalizing Child Survival) is funded by the United States Agency for International Development. inthe article, is stated that the difference is significantly different (p<0.05) by chi square. However the on recalculating chi square, the correct p value is 0.07, and for chi square with Yates continuity correction, p= 0.1 2 throat of cases and carriers. Hartley and Martin’ found that among 457 cases, approximately 50% still carried the organism at 15 days after illness onset. Weaver” studied the rate of disappearance of C. diphtheriae among 500 cases, and found that after the first week, approximately half of the cases that began the week culture positive became negative during the following 7 days. By three weeks after onset, 29% remained culture positive. The latter author also studied the rate of disappearance of C. diphtheriae in 52 camiers: by 2 weeks after identification of the carrier, 44% remained culture positive. Thus antibiotic treatment significantly shortens the duration of carriage. In addition to households, erythromycin has also been used in the setting of institutional outbreaks to successfully eradicate toxigenic C. diphtheriae.” 2. Is antibiotic prophylaxis effective in preventing secondary cases among close contacts and in reducing spread of diphtheria in the community? Ithas never been demonstrated by scientific studies that prophylaxis of all close contacts of cases more effectively prevents cither secondary cases among close contacts or further spread of diphtheria in the community, than the alternative strategy of first culturing close contacts and weating only individuals who are found to be culture positive for toxigenic C, diphtheriae, Such trials would be difficult to design and conduct in 2 manner that would produce a scientifically valid result, and might be considered unethical in Westera Europe and North America because of the concern about untreated contacts developing diphtheria, However, even without such a study, several facts taken together argue in favor of the policy of treating all household contacts, Based on studies in the era before widespread vaccination, it is known that the risk of developing clinical diphtheria in the 30 days after onset of illness in the case is at least 10 times higher among household contacts of cases than it is among the general public,’ Because the incubation period of diphtheria is usually 2 to 5 days, the highest risk of secondary cases is in the few days after the index case is identified. Rates of carriage of toxigenic C. diphtheriae of up to 25% among household contacts of cases are reported.® It usually takes a minimum of 48 hours, and often 3 to 5 days, for the laboratory to positively identify toxigenic C. diphtheriae from a throat culture. The sensitivity of culture for detection of carriers is probably not 100%, and the sensitivity of toxigenicity testing to distinguish toxigenic from nontoxigenic strains is also not 100%. Thus cases may develop while waiting for the culture result, or an undetected carrier may spread toxigenic organisms in the community. All these facts argue in favor of the WHO/UNICEF recommended policy of treating all household contacts of cases In the San Antonio outbreak described above, antibiotics were given to all household members immediately after culture, without waiting for culture results. This is also the current recommendation for diphtheria control in the United States.* 3. Will antibiotic prophylaxis induce antibiotic resistance to C. diphtheriae? ‘The WHO/UNICEF strategy recommends a single injection of benzathine penicillin as the treatment of choice for carriers, for reasons of ensuring compliance. Penicillin resistance to C. diphtheriae has never been reported in the literature, despite treatment of tens, if not hundreds, of thousands of cases and the widespread community vse of penicillins since the 1940s.*"* Studies that have examined strains that were ot cleared from the throat by course of penicillin have universally found such strains to remain sensitive to penicillin.” ‘Thus while it is possible that penicillin resistance to C. diphtheriae could occur, this is quite unlikely. There is one report of erythromycin resistance among respiratory carriers that were not rendered culture negative for C. diphtheriae by a course of erythromcyin,’* but in all other published reports of treatment of respiratory diphtheria cases and carriers, failure to eradicate the organism has not been associated with erythromcyin resistance. Plasmid-mediated erythromycin resistance to C. diphtheriae has been reported uncommonly from cutaneous diphtheria isolates,'*"* It should also be appreciated that there are many persons who are unrecognized carriers of C. diphtheriae and who receive antibiotics for various indications, without cultures for diphtheria being performed. Thus the organism is exposed to antibiotics regularly in the community, yet despite this bas remained highly susceptible to the commion antibiotics used to treat diphtheria, 4, Will antibiotic prophylaxis cause serious side effects among recipients? Penicillin is a safe, narrow spectrum antibiotic, commonly used for chronic prophylaxis (for example in patients with rheumatic heart disease and sickle cell disease). Penicillin does not cause major disturbances to the bacterial flora of the gastrointestinal tract as may be seen with broad spectrum antibiotics, Significant side effects are extremely rare, and the risk to untreated close contacts of cases of developing diphtheria, and suffering complications or death as a result, are significantly higher than the risk of suffering serious side effects from antibiotic prophylaxis. Erythromycin frequently causes abdominal discomfort, but serious side effects are also rare. In summary, the WHO/UNICEF recommendation for antibiotic treatment of all close contacts of diphtheria cases is likely to result in more effective prevention of secondary cases, and more effective prevention of further spread of C. diphtheriae in the community, than the existing practice of treating only those contacts identified as carriers of toxigenic strains. The negative impact of such increased antibiotic use is likely to be minimal. References L Doull JA, Lara H. The epidemiologic importance of diphtheria carriers. Am J Hyg 1925; $:508-529, ‘Miller LW, Older IJ, Drake J, Zimmerman S. Diphtheria immunization. Effect upon carriers and control of outbreaks. Am J Dis Child 1972; 123:197-199. Zalma VM, Older JJ, Brooks GF. The Austin, Texas, diphtheria outbreak. JAMA 1970; 211:2125-2129. McCloskey RV, Green MJ, Eller J, Smilack J. Treatment of diphtheria casriers: Benzathine penicillin, erythromycin, and. clindamycin. Ann Intem Med 1974; 81:788-791, Hartley P, Martin CJ, The apparent rate of disappearance of diphtheria bacilli from the throat after an attack of the disease. Proc R Soc Med 1920; 13:277-289. ‘Weaver GH. Diphtheria carriers. JAMA 1921; 76:831-835. Wood N, O'Gorman G. Erythromycin treatment of a diphtheria carrier epidemic in a mental deficiency hospital. Antibiotic Medicine and Clinical Therapy 1957; 4:465-469. Farizo KM, Strebel PM, Chen RT, Kimbler A, Cleary TJ, Cochi SL. Fatal respiratory disease due to Corynebacterium diphtheriae: Case report and review of guidelines for ‘managment, investigation and control. Clin Infect Dis 1993; 16:59-68. Gordon RC, Yow MD, Clark DJ, Stephenson WB. In vitro susceptibility of Corynebacterium diphtheriae to thirteen antibiotics. Appl Microbiol 1971; 21:548-549. Jackson GG, Chang S, Place EH, Finland M. Sensitivity of diphtheia bacilli and related organisms to nine antibiotics. J Pediatr 1950; 37:718-726. Lawrence DN, Facklam RR, Sotmek FO, Hancock GA, Neel JV, Salzano FM. Epidemiologic studies among Amerindian populations of Amazonia. Am J Trop Med Hyg 1979; 28(3):547-558. Maple PA, Efstratiou A, Tseneva G, Rikushin Y, Deshevoi S, Jabkola M, et al. The in-vitro susceptibilities of toxigenic strains of Corynebacterium diphtheriae isolated in northwestern Russia and surrounding areas to ten antibiotics. Joumal of Antimicrobial Agents and Chemotherapy 1994; 34:1037-1040. Mclaughlin JV, Bickham ST, Wiggins GL, Larsen SA, Balows A, Jones WL. Antibiotic susceptibility pattems of recent isolates of Corynebacterium diphtheriae Appl Microbiol 1971; 21:844-851. Zamisi I, McEntegart MG. The sensitivity of diphtheria bacilli to eigbt antibiotics. J Clin Pathol 1972; 25:716-717. 6 ‘Udgaonkar US, Dharmadhikari CA, Kulkarni RD, Kulkami VA, Pawar SG. Study of diphtheria carriers in Miraj. Indian Pediatr 1989; 26:435-439. Coyle MB, Minshew BH, Bland JA, Hsu PC. Erythromycin and clindamycin resistance in Corynebacterium diphtheriae from skin lesions. Antimicrob Agents Chemother 1979; 16:525-527. Jellard CH, Lipinski AE. Corynebacterium diphtheriae resistant to erythromycin and lincomycin [letter]. Lancet 1973; 1:156 Schiller J, Groman N, Coyle M. Plasmids in Corynebacterium diphtheriae and Giphtheroids mediating erythromycin resistance. Antimicrob Agents Chemother 1980, 18:814-821 Diphtheria Immunization Effect Upon Carriers and the Control of Outbreaks ‘Louis W, Miller, MD; J, Justin Older, MD; James Drake: and Skerwood Zimmerman, Austin, Tex 1 diphtheria epidemic in 2 small central ‘eas community centered in the slemen- ‘ar tehool. Epidemiological investigation at the seh inelused throat cultures and iene rmunzation histories of 306 of the 310 etu- sents an sta. Of these, 104 (94%) had cul tureproven diphtheria infections: 15 were rymptomatic cases and 89 were comers, Thar was no sttctica difference inthe risk of eiphtheria infection among thove with ful apse, inadequate. or ne previous éiph- teria immunizations. However, the nak of sumptomave dlipithera was 30 times a ‘or thote with none, and 21.8 times 2s ‘pet! for those with inadegaate immunize vons as for those fully immunized. Diph thera Toro heips prevent symptomatic dit tase but does not prevent the carrion state ‘er top the spre of intection, Identifying, ‘sling, and treating carriers are very im brant aspects in the contrat of diphtheria outbreaks Ww Bestved fr publ bee ith the increase in the number of cases of diphtheria in the jv Ort 1, 1972; asceptod Trop the Epidemisiogy Program Cester for Docu Cons, Auaot (Dr Miller, Older, Sate if Beers Comsat case Serve, Tesas Ste Deparsnest of Heth, Aces (De Mile, Oude Drake, and {EShense ad the Deparment of Preventive NeGiane. alumore (De. Mile) . Btomni reqvesu te Bpidemiolocy Progran, Centr fer Diseaae Conta, aunnta S883, Amer | Dig Chlld/Vel 193, March 2072 ‘Table 1—Definitions of immunization Status Saw Far ten yours. ‘completes Tega Uncemaretez Pinay seies iivee oF ere iieetOns). OF 2 primary series plot 2 boastar, completed witnin [Taped Rrrmary sees, or priory seen lus Boonie, ‘hore than ten Yours ago. primary sents (ear than tne PIECTORS) ‘ay time, Ro sibathens WS ever reeves Adapted from the Canter for Disease Gantrol* United States daring the past few years, the effect of immunization on the control of outbreaks has become an important question, In the Austin, Tex, diphtheria epidemic of 1967- 1968 eases continued to occur despite the administration of 155.200 doses of diphtheria toxoid and the con-_ comitant rise in immunization levels fof school age children from 68% to 89%, Data from the Austin outbreak suggested that a large reservoir of carriers was important io the contin- ved transmission of Corynebacterium diphtheriae. Other diphtheria out breaks have shown that epidemics oc- cur in populations with high immuni- sation levels. 4 diphtherie outbreak in an elementary schoo! in Elgin, Tes, in the spring of 1970 provided an op portunity to study the effects of im- munization on carriers and on the control of an epidemic situation. Materials and Methods When it became obvious in the Elgin {iphsheria epidemie (Older JJ etal, wnpub- Vished data} thaz cases were clustered io ‘the elementary school, « special throat cal ture and immonization survey was begun ‘here. Throat cultures ware obtained from and iminunisation status was determined for $08 of 810 students and stall. Throat ‘swabs were taken on three separave ome ‘ions from each person: April 7, April 12, and May 4. These were streaked on Loaf Jer blood seruw er Pai medium and im eubeted overnight. Cystine telurite blood agar and Tinsdale medium were used for faolation, Blek-King agar diffusion plaves ‘were sied for toxigenitity determination. Immunization status information was Diphtheria Immunisation/Miler et al 197 obtained by persona! ixtarsiew and review of available gehool 258 medieal records ‘The satus ef aach person classified as “adequate,” “lapsed.” “inadequate,” aod “none.” according to che definitions of the Genter for Disease Coosrob (Teble 1). “Any: parwoe with 4 sore throat or other tymaptoms compatible with diphtheria and 42 potitive ealere for C dipkiheriae orga nigins was dassified ae a "ease" A person ssthout erptoms br who bad « positive throat edhe for C diphtheriae organisms was classified as a Yearier,” The tarm “ Section” applied to azrone with pacitive culture regardless of Bis dinical state apd, therefore, eluded beth eases and carriers, Results When diphtheria was first diag- nosed in the elementary school,-67% of the ebildren and stall were already fully immunized, and 97% had had at least one dose of diphtheria toxoid. ‘The first case in the elementary school population was diagnosed in late Febuary 1970, and by April 8, 15 cases had occurred (Figure). Throat cultures were done on 306 children and staff; toxigenic C diph- theriae, gravis type, was isolated from 104 (34%). Fifeen of these (14%) were cases, and 88 (85%) were car viers, There was no statistical differ- ence in the risk of diphtheria infec- tion among those with full, lapsed, inadequate, or no previous diphtheria immunization (Tab:e 2), However, the risk of becoming a case was 30 times great for those with no immuniza- tion ané 11.5 times as great for those with inadequate immunizations as for TIT eT a February Maren Week of Diagnosis Dipntheria cases in Elgin, Tex, elementary schoel, spring 1970, wee anwar “Table 2.—Immunization and Culture Status of Students ang Stat, Elgin, Tex, Elementary School, Spring 1970 Diphineris teen ‘Atack Rate Immunization States Positive Fees) (per 100) (et? Tapsad 7 = o Traceguate Be 7, wat one 3 10 30.0 Teta Tor 306 3a) ciskure States “Table 3. immunization Status of Diphtheria Cases, Elgin, Tex, Elementary Setiool, Spring 1970 Diphtheria Case ‘Atak Rat (per 300) Bs. 72 = No. Immunization Satu Cases aRiax Fa z fecoerr Lapesd eer cere reer One are [_tasegate i i] Rone 3 7) Esk those with full dipbtheria immuniza- tion (Table %), Among the 104 in. fected with C dipacheriag, the Fisk of being symptomatic was 185 times as reat for those inadequately immu- iced and 37.0 times as great for those with no previous immunizations as for those who were fully immu- nied (Tabie 4), Comment ‘The imporvance of carriers in the spread of diphtheria was well docu. mented by Doull end Last in the Tout = 308 rx] Table 4.=-Risk of Symptoms and immunization Status of Students and Staff itn Positive Diphtheria Cultures, Elgin, Tex, Elementary School, Spring 1970 Symplom Aack rorat_ “Rate (per 100 Infected _Postive cuttures) + Relative Symptomatic Asymptomatic ma Immunization” Casen ‘carrer. al Zz - [Tessa ie | Ron z © 160.0 7.0 Ce eg Diphtheria Immunization’ Miller etal iy about 29% of diagnosed cases could be traced to pected ease, and the ng 80% of the cases were attrib. Wis ssvmptomatie arriem is the ulsion, Recent-epidemics in Aus foe Bigins Ten, provised ample adence that| carriers continue te pez 8, imporant roe ip the srission of diphtheria. TSS Gpuihera. towed became udlesle, it was generally “believed Yat ie induced immunity that pro- Gqted individuals from symptomatic ihe: bot not from asymptomatic in- fedsoa. This was based on the obser- Neken shat immunity is related to the NeEclization of toxin elaborated by Cadipitherice and net interference wk diphtheria infection, hy 1836, Fros. et al" alluded to F city of dbservations on record con~ ‘auming antitosie immunity snd the catier state. Nonetheless, he stated th she limited date suggested that fae 8 Be 3 any ference bee ine those individuals with and fhe without ansitexis immunity in ‘thy risk of becoming infected. More recencly, Tasman and Lane gig po: torch the hypothesis that ferdld use reduces the number of car- ‘ees. This is based on surveys that 1 Zatma VM, Older 13, Brogke 6 Vopatat Seed showed 2 steady decline in the prev lence of carriers, Since toxoid imme ation does prevent cases and since e2ses are more contagious than car- Hers the dedline in carziers could be due to the decrease in contagious cases rather than to the direct effecw: of immunization The findings in Elgin corroborate the assuznptions of Frost et al” and show that there is no difference in the Fisk of diphtheria azguisition among those with full, lapsed, inadequate, and no immunizations, However, ther also demonstrate the value of immu Risstion in reducing the risk of dis ezse and show that the protection against symptomatic iliness afforde those infected with C diphtheriae is Girectly related to their immunization status Some authors' have estimated tha if 70% or 80% of the population were adequately immunized ageinst diph- therig, spread of diphtheria would be prevented. However, diphtheria out breaks have been described in pop. lations with as mucb 29 94% of people being previously immunized = These out mown imper- tance of carriers in the spread of diphtheria, and the demonstrated talere of toxoid w prevent the eaz. TE To coneTage that the References 7125-2158, 1870, concept of herd immunity i plicable im the EAE itamunizetion will not stop the trans- reission of diphtheria, but it will limit tbe number of contagious cases. At the first appearance of a diphtheria case, control activities should be dik rected toward identifying, isolating, and treating carries, a well af toward immunizing persons with less than full immunization status. This ual approach will reduce or eliminate tbe spread of infection by reducing the number of carriers, and it will re Guce the number of cases by improv- ing the fmanization status of ex- posed indiviaal not ap Roy Moms, MD, Elgin sty healt offer, ‘seated toe nia of use aoe serange fot ‘Eeeument of camer: Miso Suan. Sip shoo! Bipeniendest, and Bn C Dake Spe ‘choo sure belped arange stare eurveyy Diskeroe, MD, sordisnied federal sate, and leeal tastance ant aspper, Will Cabins a é i iptrviews, 194 in Eitcman Tesas State Deparcoest ef Beale procased bacerolopic! speamene and Walls Jones #55, Soses Bidotam. Geigine Wigges nd Sage McLauphite,Laborsery Discs: Coe ‘er fot Denes Conteh Aten, preceme! wpe ent and perferwed al typing of C diphtheriae ganar Al iscatet Issel thront zlvures were sped ty the Banari Immunslogy ‘Gein Center cor Diseuse Gontel ‘The Austin, Texas, diphe 2 Marphy WF. Maley VE. Dick L; Continued high incencs of My diphthene ip a sell Grusized community. F ‘TiaB1-488, 1858, ibe Health Rep OV ogis Fanning 1: Ax outbreak of diphtheria ip a bighds immunised it Med J UST1-272, 1947 rs TH, Zatlin GS" As outbreak of diphtheria: A story investigation azd control Clin Pediat $550, 1906. 5, Diphtheria Sureeience Repo ‘Noo a V Communicable Diseane Centar, 1968 ‘ational € oul JA, Lara E. The epigemiclogic imporsance of diph- 06 oo, 2805 SV theria carriers. Amer v Zi ‘Pros. WH, Probiiher theia ie Baltmoore: A comparative stugr of mor prevalenes anc antiuesie immunity gp 1821 190¢ and » Gamer S Buy 2866-586, 2038 Pract Aas VWs pooner and certs ee bp 1SEP 508 Wie Vosvelkesborsn Ya,e: al: Diph- sas 1888, TEP, Problems concerning she prepay ‘therapy of dipnthena Bull THO ie eas. 5) Wiser GS, viles Ad: Topley and Milton's Principles of 5 vnily. Baltimore, Willams & Wusas Cs. 18 Dipttnere immunization’ Niier e: a) 198 4IN RB. HARDY Treatment of Diphtheria Carriers: Benzathine Penicillin, Erythromycin, and Clindamycin RICHARD V. McCLOSKEY, M.D, FAC.P., MARTHALYN J. GREEN, M1 JERRY ELLEF Asymptomatic carers of taxinogenie Corynebacterium diphtheriae were treated by ether 2 single injection of benzathine penicillin or 2 7~tay oral course of erythromycin for clindamycin, Nasopharyngeal cultures were obtained ‘rom all carriers hefore treatment and after therapy was started, The cartier state was terminated in 84% of those receiving berzathine penicilin, 92% of those receiving erythromycin, and 93% of those receiving clindamycin. These results ditter trom our previously reported Lyear study. Benzathine penicilin could be used, however, to treat diphtheria carriers when patients cannot be relied ‘upon to complete 2 7-day course of oral therapy. Clineamyein is an alternate antibiotic that wil terminate ‘the diphtheria carver state. There was no change in the sensitivity of C. diphtheriae to penieilin or erythromycin in those whasa carrier state persisted, Moossar seernoos to costtol diphtheria depend on main- taining artifcally induced antioric issmunity, early detec- ‘ion, iolation of ither symptomatic or asymptomatic patents barboring Connebacterium diphtheriae in the saasopbaryax or of the skin, and termination of the carrier state by antibioue therapy (2, 2). Eradication of C. diphe theriae from the nasopharyax aiay be difficult to accom plih (2, 3), Amibiotic rezimeas currently recommended bse aqueous procaine penicilla, oral penicilli, oF oral erythromycin for from 4 days to 1 week (3, 4) and are similar to those recommended for the treatment of active disease, Carrier oeatment has been an integral part of the contr! of recest epidemics of diphtheria in the United States (5-7). A carrer treatment program requiring multi ple injections or using the oral route for 7 days is vuloer- able to failure through lack of cooperation by the patient ‘A regia that would successfully eliminate the diphtheria carrier state with a single injection requiring only a single contact with the health care worker would promote contol of diphtheria epidemics From 1970 to 1972 we maintained a carer treatment program in San Antonio, comparing the eMlectiveness of Free, ve Secon of TAMeeiow Disses. Dennen of Micae ‘Biter Baa etic Cer. Dart ivi Puna, Peasy ES EPS Fethice Uses ec Tea acca Se TPE, Mamas nad te Goe Antonia Metropetine Beale Dice Sas 788 M.D., and JERRY SMILACK, M.D., FACE, beszathine penicillin and erythromycin in eradicating C. diphtheriae trom the casopbarynx. From 1972 to 1973 sdamycin was also used in the carrier treatment pro- gram to evaluate clindamycin as an alternative antibiotic for diphtheria carriers who may be allergic to peniclia ot ‘who might not tolerate erythromycin. Patients, Materials, and Methods When a diagnosis of diphtheria was made clinically or com firmed bacteriolopicaly, sasopbaryogeal culrures from all members of the patent's household phis the patient's comers, ulside the home were obtained by a nurse oF physician is a. sapdardied tathion previously described (5), By assignmest from 2 candom sumber list each patent's jamily une was ‘eated by one of three snethods: (1) intramuscular injection at 600.000 units (sees 2 to $ years) or 1 200000 units (older than 5 years) of beszathine penicillin; [2} erythromycin esolae bby mouth for 7 days in dosage regulated by weight 0.¢ 10 22 Eg (1 t0 50 Ibs}, 250 mg ovice a day, 22 to 45 kg [50 © 100 ibs}, 250 mg three times a day: or more than 48 kg [100 tos}, 256 mg four times 2 day: or (3) ctindamyein, 150 me by mouth four times a day for 7 days. Natopharyngeal cultures Were obtained on che eighth ant ninth day. Members of the family unit excloding the bread ‘winner, were confined to the Rome und it was known chat all cigbth and ninth day cultares were tree of diphtheria baci ‘Whenever possi aasopharyngeal culmires were obtained 30. days atiet the injection of bexzathine penicilin apd 14 days. after termination of clindamycin treatment No carers 7 ceived diphtherta andtorin. BACTERIOLOGIC BEETHODS Nasal and pharyogeal swabs were processed for isolation of G. diphiheriae by Mandard methods described previows!y (5)- Colonies with ruspicious morphology were confirmed 25 diphtheriae biochemically (8). Toxinogenicity was confirzaed. by the modified in-vitro Elek plate method (5, 10). Bacterix ‘denied 22 toxinogenic C, diphtheriae were coairmed oy the Laboratory Division, Center for Disease Control (Dr. Wall Tones) Uelius tt ae Se Teton ooapratn ad ism Se Reha ah BSS cee eeu ees aa comm 0 oe ree ee en mat ee es Se oe ee tia onlbe oe SE re enone are) ci get RN ees au tetoeoe ee See ee ea Se ee ee ya ee ae re Cs ae ternal Maisie B1:708-701, 197% fm cj six antibiotics to the cumulative percent of Coryne- octerium wiphtherice strains Killed by that antibiotic is presented io Figure 1. These in-vitro data show that all free antibiotics used in this study would be expected to tertigate the diphtheria carrier state since penicillin, eqrbromyeia, and clindamycin (among otbers) are bac tersidal for C. diphtheriae at concentrations attainable by reommended doses of each antibiotic, Wher tested by the ise metbod also, penicili, erythromycin, and clindamycin fas wel as tetracyeline) inhibit most strains of C. diph- theriae isolated during the San Antonio epidemic. ‘The population treated using any of the three regimens sas bomogeaous, being composed mostly of Latin-Amen- can children Jess than 15 years of age residing in the seutbwester part of San Antonio. ‘The data in Table 1 are derived from the teatmeot of dipbiheria carters—all confirmed bacteriological as har- ywriag dipbeberia bacilli in the nasopharyax before reeciv- ing aptibiotic treatment as prescribed in one of the three SUSCEPTIBILITY OF Zz 3 2 ‘ 04. 060 Discussion ‘Antibiotics are used in the teatment of diphtheria ta, eliminate C. diphtheriae from the nasopharyex or skin of patients with clinical disease and fo terminate the asyanpto~ ‘matic carvier state. The early use of diphtheriarantvoxin is sill the only specific metbod of treatment (1, 2). Treat: rent of the diphtheria carrier state is properly applied to those asymptomatic patients who barbor toxisogenic: diphtheria bacilli in the the upper respiratory mact or skin. All treatment programs are associated with some failures to terminate the carrier state (3, 12-14). Treat iment of the cactier state with antibiotics is superior to no treatment at all, because the carrier state_ terminated spontaneously in_only 12% of for ‘month (15). Peristing strains of C. diphtheriae did 208 Become resistant to the antibiotics used, as similarity, observed by other investigaters (11). Repository beam! thine peaiciliin can be used as an alternate method ob ‘antibiotic therapy for the diphtheria cartier state. The tsp + Volume 91 + Numbers of benzathine peaicilin may prove particularly belpful in shuations where the physicfan is unsure of patient coopera- tion Ja.2 previous report (5) benzathine pesicilin seemed tp be equally elective when compared to erythromycin in terminating the cartier state, The results of this 3-year sidy, however, show that bemaathine penicillin ix not as fective as erythromycin. Esythromysin, then, is recom- ‘pinded as the preferred antibiotic in the treatment of the éphiberia carrier state Clindamycin is 2 bactericidal antibjote for dipbtberia bacilli at concentrations tbat can e stained by recommended dose schedules. Because ‘eterocolitis may occur after the vse of clindamycin, epfbromycin is recommended as the drug of choice for treatment of the diphtberia carrier state. ecsived 21 May 1974; revision accepted 12 August 1974. Roques for reprints should be addresed to Richard. {WcGskey, MED, 3h and Reed Se, Philadelphia, PA 19167 Burrsuus L Ganast 1 Homins K: Virose, ornogny, and Imogeny: io Corynebacterium diphtherse, ann NY Ace rao ade, 1906" MeCuosey RV! Diphtheta, te Current Therapr—197¢, edited by Gon HF, Philsdcipss. W. B, Sacoder, 1974, 7. $419 5, MeCtoneay BY, Euzen Ji, Cunzw Mot ls The 1970 epideiio Of diputhera i 34m Aniosio, ANN Inier Med 1S:495-505, 1971 Mates LW, Ouoen 33, Desa J, eal: Diphtheri immaniaae ‘Yoo, Ee pes auvert and the eopirel of outbreaks, Am 7 Bu chad 12 ri99 9 ‘Zacsea VM, Oroex JH, Brooxs GF: The Austin, Texas, dipbe tena outbreak. Cini) and epidemibiogial aspect. 1404 211-21252109, 1970, . i,’ Weaver RE: Clinical Mucrobicloy, edited by ‘Fiche 2 Bekiacl Wien k iis €5, BAO pps BEL . Dremause ST, Jones WL: Problems in the wie of tho ta vise foxinopeniaty ust tot Corynebecterizm diphtherlag, An 7 (Clin Pathol 37:264:246, 1972 10, Eige SD: Te plate vrslence tt for diphtheria 7 Clin Pathol 11, MeLavomn JV, Braaum ST, Wioane GL, et al: Antibiotic suscepti patems of recent iolnies of' Corynebocierium Aiphtherive. Appi Mierobiot2):€44-851, 1971 12 Kany KD, “Hosmer EF: CTrammet of cnkinera teers riers with the ansbiose Novobiocin) (Ger) Munch Med Wochenschr 105:9125916, 1961 13. Vinoma M, Vysoney 5, Gramarr A: [The problem of meat sent of Gphtherta caries) (Ger) Z Gesamte Inn Med 16:85 a5, 1961 14, Wooo N, O'Goman G: Eerthrossycin peatocst of » dipbthesia amet epidemic io mooi delcancy hospaal dvebior Med Clin Ther 4465-489, 1957 45, Kaseuey VI: [he te of various aatbioue combinasons is the 3G coaurel of dipbitea Bact carder stun) (ish) anibiothd Siset-s68, 1964 Mecloskey at ai, + Dlontners Carters 791 8 Fatal Respiratory Disease Dug to Corynebacterium diphtheriae: Case Report and Review of Guidelines for Management, Investigation, and Control From the Dinsion of Immuniction, National Center for Prevetion Serwces Cemes for Disease Conia, lan, Georgie: nd the Heath tnd Rehabiivaive Serce ofthe Dade Counts Public Health Uni ‘he Livery of Mam. and Jackson Memonal Vedlca! Cener Mian, Fondo Karen M. Farizo, Peter M. Strebel, Robert T. Chen, Anita Kimblee, Timothy J. Cleary, and Stephen L. Cochi ‘Dramatic reductions in the inci¢ence of diphtheria and high levels of childhood vaccination in recent decades have led the United States to establish the goal of diphtheria elimination among, persons £25 years of age by the year 2000. In 1990, an unimmanized 25-month-old child died of respiratory diphtheria in Dade County, Florida, before treatment with diphtheria antitoxin could be instituted. Twenty-three asympromatic household contacts ané other close contacts of the child were identified. cultured for Corynebacterium diphtheriae, given ancimicrobial prophylaxis, and vaccinated with diphtheria toxoid when indicated. Three contacts (13%) had pharyogeal ‘cultures positive for toxigenic C, diphtheriae of the same rype as that causing infection in the ceased child, bur no additional cases developed. Although the source of infection was aot determined. three other close contacts had recently been 10 Haiti, where diphtheria is endernic. A sezological survey of 396 children <5 years of age who received care at a medical ceater in Dade County revealed that 224 lacked protective immunity to diphtheria. Anainment of the goal of iphtheria elimination among persons <25 years of age—and ultimately among all persons— will depend on the maintenance of a high level of clinical awareness of the disease, the prompt institution of preventive measures among close contacts of patients with sporadic eases, and improved vaccination levels among infants, children, and adults. In the 1920s, an average of more than {25,000 cases and $0,000 deaths duc to diphtheria were reported annually in the United States. After the widespread use of diphtheria toroid in the 1940s, the incidence of diphthena declined feavlly, with cramasic reductions in the middle 10 late 1970s In the 1980s, 27 sporadic eases of espicatory diphthe- ria were reported to the Centers for Disease Control (CDC) (range. 22:0 10 five-cases per year). including eight eases 30%) in persons <25 years of age and three fatal cases (11). ‘The sustained low incidence of diphtheria and the high levels of childhood vaccination in recent decades have led the United States to esiablish the goal of diphtheria elimination ‘among persons $25 years of age by the year 2000 [1] In spite of the extzemely low risk of indigenously acquired Fiphtheria in the United States and other industrialized ‘touniries. imporation of the organism from developing coumiries where diphtheria remains endemic poses a con stant threat. particularly among subgroups of individuals with iow vaccination levels [2-8]. Although appropriate Receed 1 Apel 1992: pvited 20 Aupest 1992, Cortspondence: De. Karen M Fara. Divsion of HIV/AIDS, Nasional ‘enter fbr Infections Deas, Centers for Disease Cond, 1800 Citon “Sa Mausiop Ett, dana, Georg 30833 Reprints Infomation Series National Centr for Prevention Services emer for Disease Cont, 1800 Clifton Roa, Salton £07. Adan. oa 3088) ined! Infections Diseses 1993165068 management of diphthena requires prompt recognition, treatment, and control measures to prevent secondary eases, few health-care providers in the United States are familiar ‘with the disease, We report the first case of respiratory diph-” theria in Dade County. Florida since 1969 (9}: describe the ‘ensuing epidemiological investigation: and review guidelines for ease management. contact tracing, and preventive mea Methods Case Investigation and Contact Tracing After notification by hospital staf the Dade County Pub- sic Health Unit initiated an investigation of e presumed ease Of diphtheria in which the patient, a 25-month-old boy. died. jet information was obtained by a retrospective review of medical records and by interviews with the child's family. ‘Attempts were made to identify al close contacts who were ‘exposed to the case-patient during his illness or within the previous week. wher secondary transmission could have 0¢- curred, In addition, to determine the source of infection. tempts were made 10 identify any clese contacts who had traveled to a diphthera-endemic area within several months before the case-patient’siliness. Close contacts were defined as household members and other persons who had intimate contact with the child (eg. relatives an friends) as well a8 hospital staff direcrly exposed t0 his respiratory secretions Hospital contacts were enumerated by infection control 0 Fanta et staff. Information on other close contacts was obtained through family interviews, After inital isis o the homes of close contacts to seen for signs and symptoms of diphtheria, ng to implement preventive measures. identified close con- tacts were ionitored for atleast | week by nome visits. cele phone contacts and clini visits. Laboratory Procedures During the first 2 weeks of the investigation.’ pharyngeal swabs obiained for culture af Corynebacterium diphiheriae were inoculated directly onte telfurite ager and Tinsdale’s medium at the hospital's laboratory. Thereafter. swabs were transported on Pai slants 10 the Florida Department of Health and Rehabilitative Services Laboratory in Jackson ville. where they were inoculated onto tellurite agar. Tinse Gale's medium, blood agar. and chocolate agar. All isolates suspected to bg C. diphtheriae were biochemically character- ized and tested for toxigenicity by the method of Elek [10] at he CDC's diphtheria reference laboratory. Serologicu Survey for Antibodies to Diphtheria Toxin, Sera from a sample of children <15 years of age who had been randomly selected fora survey of human immunodes- cieney virus (HIV) seroprevalence {1!] and who were found to be seronegative for HIV were tesied for antibodies to diph- theria toxin by toxin neutralization in VERO cells [12] at St. Christopher's Children’s Hospital in Philadelphia, These children had ceceived care at some point during the period from January through August 1990 at a community medical center that predominantly serves indigent patients in Dade ‘County and had had blood submitted to the chemistry labora tory. For each child, information on race and age group (<5 or 514 years) but not on vaccination history. was available. Case Report ‘Summary of the Case On 13 January 1990. a previously healthy. 25-month-old, unimmunized boy with a 3-day history of cough and fever presented to the pediatric emergency department at a corn munity hospital in Dade County. Flonda The child was ‘bor in the United States of parents who had immigrated fiom Haiti in 1981. He did not attend day care outside of his hhome and had no history of travel or disease exposures. At presentation he had a temperature of 39.4°C. pharyngeal ‘eqythema, wheezing. stridor, cervical swelling, and cervical lymphadenopathy. A chest radiograph showed subglottic narrowing and bilateral tung hyperinflation. tniial diagnoses were wheeting-associated acute respiratory infection and 50% of selected adolescents and adults lacked immunity to diphthe- ria toxin (38-42), with particularly low levels among the el- erty. possibly due to lack of natural exposure during the vaccine era, low rates of vaccination. and/or waning vaccine- induced immunity (39] ‘As was demonstrated by diphtheria outbreaks in Sweden and Denfhark in the 19805 [13, 43], epidemics may occur in tunvaccinated population subgroups despite widespread childhood vaccination. As has been mendioned. imporation ‘of toxigenic C, diphtheriae from developing countries where diphtheria remains endemic poses a constant threat and has accounted for most cases of diphiheria ia recent years in industrialized countries (2. 6-8. 20]. Although the source of imfection was not documented in our investigation. the hise tony of travel to Haiti among contacts ofthe case-patieat and the absence of reported diphtheria in Dade County for more ‘than 20 years suggest importation as a possibility. Because scrviage of C. diphtheriae by untreated. asymptomatic per sons lass an average of 10 days (44, 45]. some contacts may hhave had infections that cleared by the time pharyngeal swabs were ubtained for culture. Furthermore, not all con- CHD 1999316 January, 2c were located: those who could not be found included ‘one woman who frequently traveled to Haiti, Suudies of the molecular biology of diphtheria suggest that conversion of nontoxigenic C, diphtheriae to a toxin-producing strain by tysogenic wansfer of the gene coding for toxigenicity could have occurred [4]. but n0 nontoxigenic strains were recov- ered from conisets. Recommendations for Prevention and Control of Diphtheria ‘The need for rapid clinical and public health responses 10 diphtheria. a potentially fal but rare disease. prompted us to review the recommendations and underlying rationale for the management of cases. the investigation of contacts. and the institution of preventive measures. On the basis of our review. we developed an algorithm to guide management ‘and investigation of diphtheria (figure 1) should suspected or proven eases occur in the future. Glnical Diagnosis Because respiratory diphtheria may progress rapid! high index of suspicion needs to be maintained, Classical respiratory diphtheria is characterized by insidious onset, membranous pharyngitis with fever, enlarged anterior cervi- cal lymph nodes, and edema of surrounding soft tissue. whieh gives rise oa “bull neck” appearance [14. 16. 47]. Although not always present. the membrane is typically ‘pay, thick, fibrinous, and firmly adherent. Laryngeal diph- theria is characterized by gradually increasing hoarseness and stridor and most commonly occurs as aa extension of pharyngzal involvement in children [14, 47]. Laboratory Dizgnosis Because the tecesful isolation of C: diphtheriae depends ‘on rapid inoculation of special culture media. the laboratory should be notified as son 2 the diagnosis fs suspected. With routinely available throat or nasopharyngeal swabs. samples preferably should be obiained from the membrane (if pres- ent) of from beneath its edge. Although nasal diphtheria in the absence of pharyngeal involvement is uncommon. cule turing of both nasal and pharyngeal secretions may improve the rate of isolation of C. diphiherige (5. 51, 52}. Methods for the bacteriologic diagnosis of diphtheria have been described in detail elsewhere [53-55] In brief. a confirmatory diagno- sis may tae several days and requires culture and isolation of the organism. biochemical typing, and toxigenicity testing. In some instances. a presumptive disenosis may be made within <26 hours on the basis of cellular morphology on a methylene blur-siained smear of growth obtained after inco- bation on Lueffct or Pai medium [54 55]. However. micron 10 1993.46 anwar Invenigation and Comtel of Drphihens Table 2. Results of selected surveys of carriers of tonigenic C. diphiherae, by setting and {eat No.of eamienina. No.ef of persons eres Sening. years) Lecatian reference] cater (carage rite.) Comments Hovwehold 86 Stocbnotm. Sweden (24) ona Swabs from householé and uber close comets were ‘ulus was Manchest. United Kingdom (6) 0K) is7S-1982 Ouran, Canad 25) 22805) 7 197 London, Unites Kongsor (26) yas) ‘The ete patie had 2 mild ecurent sore throat for >2y. 1469-1970 Cheapo, noi (27) 173.019) Information on vxigeniy of soiate among camer, as aot availabe ro) Dade Coumy, Fons (9) 2278327) Seto! 18s (Onan, Canad (8) DINA( Swabs from classmates and teacher ef ne ease> patient wer eluted. 985 Manchester, United Kiagsom 6) 8326) 1980 ‘users. Gres (19) O/895(...) ‘Swabs rom random sample of chien ln seecied ‘pomary schools were clare. ws Birmingham, United Kings [28] 91516. 9 1970 Athens, Greece [18] 7B Seabs from a rindom sample of ehileren im selected ‘nary shools were culated 70 Eigin, Teas (29) sens.) Hogi 1904-1985 Goebor, Sweden [22 oys28 Swabs From hospital employess wh cared for iphihera patents were culture. 19s Manchester United Kingdom [6} OKA ‘Swabs fom hoxptl employers Who cared fr he ‘auerpauent were eutured wn Milwmukes. Wisconsin (30) MMA Swabs from hespual employees who cared oe Ne ‘aserpaent were eultred Wesuminster. United Kingdom (7) 078i ‘Swabs from nospal contacts of ihe easepavent ant ‘of wo hospatzed caries were cule nui, Canada (21) OAC Swabs from 86 persons. inching unspecified ‘number of howl employees. pauenc. and household cones, were evlired Birminghara. Usind Kington [2 oA. “Suan from nine patient 86d eight hospital employee were cutie Pontypool. ite Kingdom [12] 36/824 (4) (0F 463 patents and 341 employers. 36 (75) an6 2 {06%} respectively, were infeed (aa Kingdom (33) 29/84 (NA) fan unspessed numberof employess and 161 pallens, Oand29( 188) respecuvely, were infeed, Garebory Sweden (22) ONA(. 2) More than 17.000 gua for entire were obisined fom an vnspecied namber of pees. ‘Westminster. Unied Kingdom (7) SINAINAD More tan 8,000 swans for eutisre wert obcatnee {fom an unepecfied numberof persons. Five infected perons wer identi all of whom had had iret conta: witha easegaiem. Hodeida. Vemen Arab Republi [34] oa.) ‘swabs fom children with no known exposure 19 jheca who visted an ouipatiens cine were cular, Manchester. United Kings (21) 3424.00 (0.1) Manchesier United King (3) 2/>3,000 (<1) Swabs for eulure were sowines from noeseholé and ehoolsoncais ane from persion! with no ‘decumentedexponue to = easepaient. Most camer were shool contac srapama (23) 77.600 60.1) cyngea! cultures for suspected sreprococeal Ss ndate et ta are non usable 1D 1995516 (lanuay; Suspected or : proven diphtheria * Begin antimicrobial therapy? lotty + Provide active Immunization with diphtheria Ne health department toxold during convalescence’ Boe ae See eee Identity close contacts* *| None i T Assess and monitor for Obtain cultures: for C. diphtheriae! 2 sere +| stop T antimicrobial eee ive} Sdoses r= = Administer immectate * Avoid close contact with inadequately vaccinated persons + Identity clowe contacts and proceed 7 moasures described x toxold and + Repeat cultures a minimum of two weeks completa feodngss ‘schedule + after completion of antimicrobials to assure eradication of the organism |. Respiratory diphthviz: recommencasons for case mazagcment and investigation of elose contaes. “Mainain iclation unt ination of the organism is demonstrated My neyative culture of tO ‘brains a lea 24 hours apart alice completion of Antimicrobial thempy (46). "Roth naz and pharngeal sabe thoald be obtained for culture "Equine diphihena antioxin ean be obtained {tom either the Division of Immunization. Center for Disease Control. Adanta (ilephone 04-63-2888), of Connaught Laboratories. Switiwatee. PA. Before its administration. patients should be tested (or sensitivity wo hore serum and. if neceuary. desensitized. The recommenced Josage and route of administration depead on the cxient and duration of disease. Deuiled recommendations ean be vbained from the package inser and other publications (14, 4648). ‘Anuimicobial therapy is nota sibattut for anttoxin teaunent. {Intramuscular proce penicillin G (25.000 to 50.000 units/[kg-dj oe children and 1.2 milion nits/d for adults. n two divided doses) or Parmnteral erythromycin (40-50 mg/fkgd). with a maximum of 2 pf) has bern recommended (46, 49} until the patient can swallow somiontbiy, at which point oral ervubromycin in four divided doves [46,49] or ora penicilin V (123-250 mg four simes daly) (29] may be substituted fora recommended ‘oul eaiment period of 14 days [46,49], "Vaccination is required because clinical diphtheria docs not ‘ecexaily confer immunity. “Close coniaexs include Rowsehold members and other penons with a history of direct comact with a ccbepatient (eg. creuker. relatives of fiends who reglacty vit the home) a6 well ax medical suf exposed 10 ona or respiraory serio af Sarat WA spe de of nama betaine pri 4OD.00 is pn . 202, 13, Henattand’Gahembaths Wosenoer sf Bipbers 08, Ti: Weer, G. Mes J. Tele Dia 30: 128 (a) 07 Hi Matted: F Wa dae icy. 3G Bu) Am Js Pun Matte x0: Bye, tab. US. Picea DIPHTHERIA CARRIERS WEAVER wea presence of diphtheria and emphasizes the difiaxip Sh ercreating the deease * ome In distincuoa tothe bacilli from “heslthy"ar gontact carriers, those cultivated from pene, have recently had diphtheria, “convalescent” cattiegt for those who have been fn contact with cides of dip theria, “contact” earriers, are virulent in a lexge pro portion. * : ey ‘The committee af the Massachusetts 08 Boards of Health * decided’ that bacilli from'persoa: who had been in close contact with cases of diphtherts are usually virulent. I} concluded :frdai“my@nidy Ghat such cultures were practically

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