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Diphtheria: Another risk of travel
Journal of Infection (I992) zS, 307-3 IO
CASE REPORT Diphtheria: another risk of travel H e l e n Antos, L i n d s a y C. Mollison,* M i c h a e l J. Richards, A l a n L. B o q u e s t a n d F r e d e r i c k A. Tosolini
Austin Hospital, Studley Road, Heidelberg, Victoria 3084, Australia Accepted for publication 9 March I992 Summary A 19-year-old woman presented with cellulitis of her foot IO days after returning from Bali. Swabs of a central necrotic area grew toxigenic Corynebacterium diphtheriae biotype gravis. The patient was treated with parenteral penicillin and made a complete recovery. Diphtheria immunisation should be regularly updated for travellers to the tropics. Clinical and laboratory recognition of this infection is essential for appropriate public health measures to be undertaken.
Introduction D i p h t h e r i a has b e c o m e a rare disease in developed countries following the widespread use of immunisation and i m p r o v e m e n t in socioeconomic circumstances. 1 H o w e v e r , cutaneous diphtheria remains a p r o b l e m in those with poor personal and domestic hygiene, b o t h in temperate climates 2 and in the tropics. 3 T h e s e rare cases have usually been associated with travel to endemic areas.4 W e report a case of cutaneous diphtheria in an i m m u n i s e d traveller and discuss the issues involved in diagnosis and management.
Case report A I 9 - y e a r - o l d w o m a n complained of a painful, swollen, erythematous right foot for I day. F o u r days earlier, while walking t h r o u g h long grass, she had the sensation o f something crawling on her foot and believed she might have been bitten b y a spider although none was seen. T h e patient was otherwise well, with no systemic s y m p t o m s . She was e m p l o y e d as an apprentice chef and was a n o n - s m o k e r and a social drinker. H e r only medication was the oral contraceptive pill and a salbutamol inhaler for mild asthma. An area of poorly defined cellulitis was n o t e d on the d o r s u m of her right foot. Oral flucloxacillin was c o m m e n c e d b u t on the following day the cellulitis was m o r e extensive. Analgesia was prescribed and the patient was advised not to work. T w o days later she complained of an increase in pain, having gone to w o r k in open footwear on the previous day. O n examination she looked well, her t e m p e r a t u r e was 36"2 °C, BP I I 5 / 7 0 m m H g , pulse 8 8 / m m and respiratory rate I 8 / m i n . She had a swollen, tender, e r y t h e m a t o u s area of cellulitis on the d o r s u m o f her foot with a central black area of superficial necrosis (Plate I). T h e r e was no * A d d r e s s correspondence to : D r L. Mollison, D e p a r t m e n t of Medical Microbiology, A u s t i n Hospital, Studley Road, Heidelberg, Victoria 3084, Australia. oi63-4453/92/o6o3o7+o4 13
$08.00/0
© I992 T h e British Society for the Study of Infection JIN 25
308
H. ANTOS E T A L .
lymphangitis or inguinal lymphadenopathy. Throat, nose and respiratory examinations were normal. She was admitted to the ward and treated with rest, elevation of the limb and intravenous penicillin G r 2 g q.i.d, and flucloxacillin I g q.i.d. After 2 days the cellulitis was improving and the medication was changed to oral flucloxacillin 5o0 mg q.i.d. At that time culture of the central necrotic area revealed Corynebacterium diphtheriae biotype gravis, and an urgent Infectious Diseases consultation was arranged. When questioned further she said she had been in Bali for 16 days and had returned Io days before presentation. A girlfriend with whom she had travelled had complained of a very sore throat for 4 days before their return to Australia, when she had been treated with antibiotics. She was now well. Our patient gave a history of diphtheria immunisation as a child. Although she had received a tetanus booster during the previous year, the last diphtheria booster was likely to have been in childhood. Although well, the patient was moved to a single room and full isolation procedures were instituted. Treatment with intravenous penicillin G I'2 g 4 hourly was continued for 4 days. Further swabs were taken from her wound, throat and nasopharynx, but none grew C. diphtheriae. She was then discharged to complete I4 days total therapy with penicillin V 5oo mg q.i.d. When reviewed 48 h after the completion of antibiotics she was completely well. Further swabs at this stage established that she was not a carrier and she returned to work. T h e health department was notified of the case and family and community contacts were traced. Swabs from these persons were all negative for C. diphtheriae. Staff members who had nursed the patient were encouraged to update their diphtheria immunisation with A D T .
Microbiology A swab taken from the central necrotic ulcer on the right foot was received in Stuart's transport medium. Gram-staining revealed pus cells 2 + , with pleomorphic Gram-positive bacilli 2 + and a few Gram-positive cocci. T h e swab was plated on Horse Blood Agar and after overnight incubation at 36 °C two colonial forms were seen. One was a beta haemolytic streptococcus identified as Streptococcus pyogenes. T h e r e were also shiny, grey colonies resembling diphtheroids which proved to be Gram-positive rods. These colonies were further plated onto Tinsdale's agar and a range of biochemical tests, using the API Coryne system (API System, Montalieu-Vercieu, France) was performed. T h e organism was identified as C. diphtheriae. An Elek toxin detection plate was set up and toxin-antitoxin precipitin lines were detected after 48 h incubation. These findings were confirmed by the Microbiological Diagnostic Unit, University of Melbourne, which fully identified the organism as C. diphtheriae biotype gravis. Discussion
T h e isolation of this toxigenic strain of C. diphtheriae was the first in Victoria since I984 and the patient was the first with clinical disease since I983, when a traveller presented with a foot ulcer after having been 'bitten by a spider in
Journal of Infection
i~ ¸¸ i
i
i
! :i
Plate I
~ ~
i: i: ii i!? ii i? !! !i?
Plate I. Right foot shows swollen, erythematous area of cellulitis with central necrosis.
H. ANTOS
ET AL.
( F a c i n g p. 308)
Diphtheria--another travel risk
309
Bali' (personal communication, D r J. Forsyth). T h e last case of pharyngeal diphtheria was in I973, and the last case o f pharyngeal carriage was in I984 in a refugee (J. F.). O u r patient had no evidence of systemic toxicity and her clinical o u t c o m e was uneventful. H o w e v e r , the case raises a n u m b e r of issues concerning diagnosis, therapy and public health. T h e diagnosis of cutaneous diphtheria was not considered w h e n this patient presented. T h e disease is u n c o m m o n and therefore m a y not be suspected. 4 It should be included in the differential diagnosis of skin lesions of travellers returning from the tropics. M o s t cases are sporadic and imported. ~ C o m b i n e d t e t a n u s - d i p h t h e r i a vaccine should be offered to travellers, 5 rather than tetanus toxoid alone. Experience of cases overseas shows that herd i m m u n i t y does not p r e v e n t carriage or transmission of the organism 4 and even for non-travellers diphtheria toxoid boosters should be offered in order to maintain personal protection w h e n e v e r tetanus toxoid is being administered. 5 W h e n it affects the pharynx, C. diphtheriae causes an infectious disease with a high mortality. 3 All cases m u s t be isolated until swabs establish that the organism has been eradicated. Whilst cutaneous lesions are the least likely to cause serious toxic disease s they pose the greatest risk of spread to the e n v i r o n m e n t 6 and the patient m u s t be isolated. Spread within hospitals to staff m e m b e r s appears to be a small risk, 7 b u t staffin contact with cases should have their i m m u n e status maintained. N o n - i m m u n i s e d staff and other contacts should be s w a b b e d , offered antibiotic prophylaxis and started on a p r i m a r y course of immunisation. T h e clinical picture m a y have been attributed incorrectly to S. pyogenes b u t further investigation of the ' d i p h t h e r o i d ' r e s u l t e d in the identification of C. diphtheriae. O f 947 cases of cutaneous diphtheria described b y Harnisch, 2 S. pyogenes was f o u n d concomitantly in 73 %. F u r t h e r m o r e , colonisation with C. diphtheriae o f skin lesions primarily due to other insults or organisms is well recognised. In o u r patient we believe the typical diphtheritic appearance of the lesion is in favour of a p r i m a r y pathogenic role for C. diphtheriae. Colonisation, however, w i t h o u t infection or toxigenic effect is p r o b a b l y c o m m o n e r in travellers than clinical disease and such carriers m a y pose a greater overall infective threat to the c o m m u n i t y than the occasional clinical case. All microbiology laboratories m u s t be able to isolate and identify C. diphtheriae and the identification of toxin p r o d u c t i o n is an important aspect, enabling appropriate m a n a g e m e n t of the patient and contacts. (We express our thanks to the staff of the Microbiological Diagnostic Unit, University of Melbourne, who confirmed the characteristics and identity of this organism, and to Drs Rosco Taylor and John Carnie of the Health Department of Victoria who confirmed the details of the community follow-up. Mr Robert Jones is thanked for permission to report this case, and Dr Jocelyn Forsyth is thanked for identifying other recent cases.) References
i. Kantes W. Diphtheria in Europe. J Hyg I984; 93: 432-437. 2. Harnisch JP, Tronca E, Nolan CM, Turck, M, Holmes KK. Diphtheria among alcoholic urban adults. Ann lntern Med I989; iII: 7r-82. 13-2
310
H. ANTOS E T AL.
3. MacGregor RR. Corynebacterium diphr_heriae, In: MandeU GL, Douglas RG Jr, Bennett JE, Eds. Principles and practice of infectious diseases, 3rd ed. New York: Churchill Livingstone, 199o: 1574-1581. 4. Bowler ICJ, Mandal BK, Schlecht B, Riordan T. Diphtheria--the continuing hazard. Arch Dis Child 1988; 63: 194-21o. 5. N H M R C Immunisation procedures, 4th ed. Canberra: Australian Government Publishing Service, 1991: x6-29. 6. Koopman JS, Campbell J. The role of cutaneous diphtheria infections in a diphtheria epidemic, ff Infect Dis 1975; 131: 239-244. 7. Larsson P, Brinkhoff B, Larsson L. Corynebacterium diphtheriae in the environment of carriers and patients. J Hosp Infect 1987; IO: 282-286.
CASE REPORT Diphtheria: another risk of travel H e l e n Antos, L i n d s a y C. Mollison,* M i c h a e l J. Richards, A l a n L. B o q u e s t a n d F r e d e r i c k A. Tosolini
Austin Hospital, Studley Road, Heidelberg, Victoria 3084, Australia Accepted for publication 9 March I992 Summary A 19-year-old woman presented with cellulitis of her foot IO days after returning from Bali. Swabs of a central necrotic area grew toxigenic Corynebacterium diphtheriae biotype gravis. The patient was treated with parenteral penicillin and made a complete recovery. Diphtheria immunisation should be regularly updated for travellers to the tropics. Clinical and laboratory recognition of this infection is essential for appropriate public health measures to be undertaken.
Introduction D i p h t h e r i a has b e c o m e a rare disease in developed countries following the widespread use of immunisation and i m p r o v e m e n t in socioeconomic circumstances. 1 H o w e v e r , cutaneous diphtheria remains a p r o b l e m in those with poor personal and domestic hygiene, b o t h in temperate climates 2 and in the tropics. 3 T h e s e rare cases have usually been associated with travel to endemic areas.4 W e report a case of cutaneous diphtheria in an i m m u n i s e d traveller and discuss the issues involved in diagnosis and management.
Case report A I 9 - y e a r - o l d w o m a n complained of a painful, swollen, erythematous right foot for I day. F o u r days earlier, while walking t h r o u g h long grass, she had the sensation o f something crawling on her foot and believed she might have been bitten b y a spider although none was seen. T h e patient was otherwise well, with no systemic s y m p t o m s . She was e m p l o y e d as an apprentice chef and was a n o n - s m o k e r and a social drinker. H e r only medication was the oral contraceptive pill and a salbutamol inhaler for mild asthma. An area of poorly defined cellulitis was n o t e d on the d o r s u m of her right foot. Oral flucloxacillin was c o m m e n c e d b u t on the following day the cellulitis was m o r e extensive. Analgesia was prescribed and the patient was advised not to work. T w o days later she complained of an increase in pain, having gone to w o r k in open footwear on the previous day. O n examination she looked well, her t e m p e r a t u r e was 36"2 °C, BP I I 5 / 7 0 m m H g , pulse 8 8 / m m and respiratory rate I 8 / m i n . She had a swollen, tender, e r y t h e m a t o u s area of cellulitis on the d o r s u m o f her foot with a central black area of superficial necrosis (Plate I). T h e r e was no * A d d r e s s correspondence to : D r L. Mollison, D e p a r t m e n t of Medical Microbiology, A u s t i n Hospital, Studley Road, Heidelberg, Victoria 3084, Australia. oi63-4453/92/o6o3o7+o4 13
$08.00/0
© I992 T h e British Society for the Study of Infection JIN 25
308
H. ANTOS E T A L .
lymphangitis or inguinal lymphadenopathy. Throat, nose and respiratory examinations were normal. She was admitted to the ward and treated with rest, elevation of the limb and intravenous penicillin G r 2 g q.i.d, and flucloxacillin I g q.i.d. After 2 days the cellulitis was improving and the medication was changed to oral flucloxacillin 5o0 mg q.i.d. At that time culture of the central necrotic area revealed Corynebacterium diphtheriae biotype gravis, and an urgent Infectious Diseases consultation was arranged. When questioned further she said she had been in Bali for 16 days and had returned Io days before presentation. A girlfriend with whom she had travelled had complained of a very sore throat for 4 days before their return to Australia, when she had been treated with antibiotics. She was now well. Our patient gave a history of diphtheria immunisation as a child. Although she had received a tetanus booster during the previous year, the last diphtheria booster was likely to have been in childhood. Although well, the patient was moved to a single room and full isolation procedures were instituted. Treatment with intravenous penicillin G I'2 g 4 hourly was continued for 4 days. Further swabs were taken from her wound, throat and nasopharynx, but none grew C. diphtheriae. She was then discharged to complete I4 days total therapy with penicillin V 5oo mg q.i.d. When reviewed 48 h after the completion of antibiotics she was completely well. Further swabs at this stage established that she was not a carrier and she returned to work. T h e health department was notified of the case and family and community contacts were traced. Swabs from these persons were all negative for C. diphtheriae. Staff members who had nursed the patient were encouraged to update their diphtheria immunisation with A D T .
Microbiology A swab taken from the central necrotic ulcer on the right foot was received in Stuart's transport medium. Gram-staining revealed pus cells 2 + , with pleomorphic Gram-positive bacilli 2 + and a few Gram-positive cocci. T h e swab was plated on Horse Blood Agar and after overnight incubation at 36 °C two colonial forms were seen. One was a beta haemolytic streptococcus identified as Streptococcus pyogenes. T h e r e were also shiny, grey colonies resembling diphtheroids which proved to be Gram-positive rods. These colonies were further plated onto Tinsdale's agar and a range of biochemical tests, using the API Coryne system (API System, Montalieu-Vercieu, France) was performed. T h e organism was identified as C. diphtheriae. An Elek toxin detection plate was set up and toxin-antitoxin precipitin lines were detected after 48 h incubation. These findings were confirmed by the Microbiological Diagnostic Unit, University of Melbourne, which fully identified the organism as C. diphtheriae biotype gravis. Discussion
T h e isolation of this toxigenic strain of C. diphtheriae was the first in Victoria since I984 and the patient was the first with clinical disease since I983, when a traveller presented with a foot ulcer after having been 'bitten by a spider in
Journal of Infection
i~ ¸¸ i
i
i
! :i
Plate I
~ ~
i: i: ii i!? ii i? !! !i?
Plate I. Right foot shows swollen, erythematous area of cellulitis with central necrosis.
H. ANTOS
ET AL.
( F a c i n g p. 308)
Diphtheria--another travel risk
309
Bali' (personal communication, D r J. Forsyth). T h e last case of pharyngeal diphtheria was in I973, and the last case o f pharyngeal carriage was in I984 in a refugee (J. F.). O u r patient had no evidence of systemic toxicity and her clinical o u t c o m e was uneventful. H o w e v e r , the case raises a n u m b e r of issues concerning diagnosis, therapy and public health. T h e diagnosis of cutaneous diphtheria was not considered w h e n this patient presented. T h e disease is u n c o m m o n and therefore m a y not be suspected. 4 It should be included in the differential diagnosis of skin lesions of travellers returning from the tropics. M o s t cases are sporadic and imported. ~ C o m b i n e d t e t a n u s - d i p h t h e r i a vaccine should be offered to travellers, 5 rather than tetanus toxoid alone. Experience of cases overseas shows that herd i m m u n i t y does not p r e v e n t carriage or transmission of the organism 4 and even for non-travellers diphtheria toxoid boosters should be offered in order to maintain personal protection w h e n e v e r tetanus toxoid is being administered. 5 W h e n it affects the pharynx, C. diphtheriae causes an infectious disease with a high mortality. 3 All cases m u s t be isolated until swabs establish that the organism has been eradicated. Whilst cutaneous lesions are the least likely to cause serious toxic disease s they pose the greatest risk of spread to the e n v i r o n m e n t 6 and the patient m u s t be isolated. Spread within hospitals to staff m e m b e r s appears to be a small risk, 7 b u t staffin contact with cases should have their i m m u n e status maintained. N o n - i m m u n i s e d staff and other contacts should be s w a b b e d , offered antibiotic prophylaxis and started on a p r i m a r y course of immunisation. T h e clinical picture m a y have been attributed incorrectly to S. pyogenes b u t further investigation of the ' d i p h t h e r o i d ' r e s u l t e d in the identification of C. diphtheriae. O f 947 cases of cutaneous diphtheria described b y Harnisch, 2 S. pyogenes was f o u n d concomitantly in 73 %. F u r t h e r m o r e , colonisation with C. diphtheriae o f skin lesions primarily due to other insults or organisms is well recognised. In o u r patient we believe the typical diphtheritic appearance of the lesion is in favour of a p r i m a r y pathogenic role for C. diphtheriae. Colonisation, however, w i t h o u t infection or toxigenic effect is p r o b a b l y c o m m o n e r in travellers than clinical disease and such carriers m a y pose a greater overall infective threat to the c o m m u n i t y than the occasional clinical case. All microbiology laboratories m u s t be able to isolate and identify C. diphtheriae and the identification of toxin p r o d u c t i o n is an important aspect, enabling appropriate m a n a g e m e n t of the patient and contacts. (We express our thanks to the staff of the Microbiological Diagnostic Unit, University of Melbourne, who confirmed the characteristics and identity of this organism, and to Drs Rosco Taylor and John Carnie of the Health Department of Victoria who confirmed the details of the community follow-up. Mr Robert Jones is thanked for permission to report this case, and Dr Jocelyn Forsyth is thanked for identifying other recent cases.) References
i. Kantes W. Diphtheria in Europe. J Hyg I984; 93: 432-437. 2. Harnisch JP, Tronca E, Nolan CM, Turck, M, Holmes KK. Diphtheria among alcoholic urban adults. Ann lntern Med I989; iII: 7r-82. 13-2
310
H. ANTOS E T AL.
3. MacGregor RR. Corynebacterium diphr_heriae, In: MandeU GL, Douglas RG Jr, Bennett JE, Eds. Principles and practice of infectious diseases, 3rd ed. New York: Churchill Livingstone, 199o: 1574-1581. 4. Bowler ICJ, Mandal BK, Schlecht B, Riordan T. Diphtheria--the continuing hazard. Arch Dis Child 1988; 63: 194-21o. 5. N H M R C Immunisation procedures, 4th ed. Canberra: Australian Government Publishing Service, 1991: x6-29. 6. Koopman JS, Campbell J. The role of cutaneous diphtheria infections in a diphtheria epidemic, ff Infect Dis 1975; 131: 239-244. 7. Larsson P, Brinkhoff B, Larsson L. Corynebacterium diphtheriae in the environment of carriers and patients. J Hosp Infect 1987; IO: 282-286.