British Journal of Neurosurgery
ISSN: 0268-8697 (Print) 1360-046X (Online) Journal homepage: http://www.tandfonline.com/loi/ibjn20
Ventriculitis and hydrocephalus caused by Candida albicans successfully treated by antimycotic therapy and cerebrospinal fluid shunting Abdulhakim Jamjoom, Zain Al-Abedeen Jamjoom, Saleh Al-Hedaithy, Abdulfatah Jamali, Naim-ur-Rahman & Tajuddin Malabarey To cite this article: Abdulhakim Jamjoom, Zain Al-Abedeen Jamjoom, Saleh Al-Hedaithy, Abdulfatah Jamali, Naim-ur-Rahman & Tajuddin Malabarey (1992) Ventriculitis and hydrocephalus caused by Candida albicans successfully treated by antimycotic therapy and cerebrospinal fluid shunting, British Journal of Neurosurgery, 6:5, 501-504, DOI: 10.3109/02688699208995043 To link to this article: http://dx.doi.org/10.3109/02688699208995043
Published online: 06 Jul 2009.
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ibjn20 Download by: [McMaster University]
Date: 14 April 2016, At: 16:28
British Journal of Neurosurgely (1992) 6 , 501-504
SHORT REPORT
Downloaded by [McMaster University] at 16:28 14 April 2016
Ventriculitis and hydrocephalus caused by Candida albicans successfully treated by antimycotic therapy and cerebrospinal fluid shunting ABDULHAKIM JAMJOOM, ZAIN AL-ABEDEEN JAMJOOM, SALEH AL-HEDAITHY,* ABDULFATAH JAMALI, NAIM-UR-RAHMAN & TAJUDDIN MALABAREYt Division of Neurosurgely, and *Departments of Microbiology and fRadiology, King Khalid University Hospital, Riyadh, Saudi Arabia
Abstract A unique case of Candida albicans ventriculitis and hydrocephalus in the absence of any evidence of systemic candidiasis or immunosuppression is reported. Initial treatment with CSF shunting and intravenous antimycotic therapy appeared to have eradicated the infection. Recurrence occurred 5 months after discharge and this was treated by intravenous and intrathecal antimycotic therapy in addition to removal of the shunt system, external ventricular drainage and then replacement of the shunt. A concomitant pyogenic brain abscess responded to burrhole aspiration and antibiotics. The role of mannan antigen monitoring is discussed.
Key words: Candida albicans, hydrocephalus, mannan antigen, shunt infection, venm'culitis.
Introduction
Involvement of the central nervous system (CNS) with Candida occurs in 48-64% of the cases with dessiminated candidiasis'.* and it is not uncommon in the immunocompromised patient, occurring in 1.7% of cases with AIDS.3 Cerebral candidiasis in the absence of immunosuppression and without systemic manifestations is very We report a unique case of a previously healthy patient who developed Candida albicans ventriculitis and hydrocephalus. The infection and the recurrence were treated by cerebrospinal fluid (CSF) shunting and antimycotic therapy. In addition to stressing the rarity of isolated cerebral candidal infection in patients with normal immunity, the aim of this paper is to demonstrate the insidious clinical course of the disease, the management difficulties, and the
value of monitoring the mannan antigen during treatment.
Case history A 17-year-old female presented to our hospital with 3 months history of headaches, vomiting and dizziness. She was drowsy and apyrexial. She had bilateral papilloedema with normal visual acuity. Her gait was ataxic and had no clinical signs of meningism. C T showed evidence of hydrocephalus with no focal lesion or abnormal enhancement. An urgent right ventriculo-peritoneal (VP) shunt was performed. The ventricular CSF obtained at operation had a protein of 0.28 g/l, sugar of 1.7 mmol/l and WBC of 2 x 103/l. CSF microscopy and culture demonstrated Candida albicans. Fur-
50 l
Downloaded by [McMaster University] at 16:28 14 April 2016
502
Abdulhakim Jamjoom et al.
ther investigations showed that the patient had a negative blood culture, negative HIV status, normal serum immunoglobulins and a normal cell-mediated immunity response. Treatment was started with intravenous flucytosine (2 g/6 h) and amphotericin B (10 mglday). The dose of the latter was increased by 5 mg every week reaching 30 mg/day. Immediately postoperatively the patient became more alert; however, her headache and vomiting persisted. C T 3 days later showed a collapsed right lateral venticle while the left ventricle was still dilated. This was managed by catheterization of the left frontal horn and connecting the catheter to the pre-existing functioning right VP shunt. The antimycotic therapy was continued for 51 days even though the CSF had become sterile 21 days after starting treatment. She was discharged 59 days after admission. At the time she was alert, orientated with no deficits. The mannan antigen was negative in her CSF and blood and C T showed collapsed ventricles. Over the next 4 months the patient was reviewed as an out-patient twice. She remained clinically well. Five months after discharge, the patient was readmitted with 4 weeks history of recurrence of her previous symptoms. C T showed dilated right temporal horn with increased size of ventricles but no abnormal enhancement. The ventricular CSF had protein of 1.27 g/l, sugar of 1.9 mmol/l and WBC of 64 X 103/l. The CSF showed on microscopy and grew on culture Candida albicans again. In addition, the mannan antigen became positive in the CSF and blood. The patient was re-started on intravenous flucytosine and amphotericin B. Unfortunately, over the next 2 weeks, she deteriorated gradually, becoming slow, generally weak and developed dysconjugate gaze. The CSF continued to grow Candida albicans and the mannan antigen remained positive in the CSF and serum. Therefore, 20 days following readmission, the shunt tubes were removed and bilateral external ventricular drains were inserted. Treatment with flucytosine continued; however, amphotericin B was given intra-thecally (dose 0.25 mglday) and itraco-
nazole (100 mg/day) orally. Clinically the patient remained stable, drowsy with very little speech, anorexic and generally weak. Her recovery was complicated by a left frontal Staphylococcus aureus abscess which had originated from a thrombophlebitis in the left arm and which responded to treatment by burrhole aspiration, flucloxacillin and ceftrioxone. Following 21 days of external drainage, the CSF culture and mannan antigen had been negative on three occasions. The drains were then removed and bilateral VP shunts were inserted. Postoperatively, treatment with flucytosine and itraconazole was continued for a further 2 months. Her clinical recovery onward was good. The patient was able to communicate and mobilize. CT showed resolution of the frontal abscess and the ventricles were small. The patient was discharged 85 days after readmission. She was followed up for 6 months and during that time her dysconjugate gaze, ataxia and dysarthria improved slightly. In addition, the CSF mannan antigen remained negative.
Discussion Cerebral candidiasis has become the most prevalent cerebral mycosis diagnosed at autRecognized predisposing factors include: chemotherapy for cancer or transplanatation, immune deficiency syndromes, drug abuse, parenteral nutrition and intensive therapy treatment, gastrointestinal pathology and abdominal surgery, ageing, antibiotics and steroid therapy.*+’ The case presented here had none of the above risk factors and showed no evidence of extracranial disease. The patient had ventriculitis which caused hydrocephalus. The latter is a rare complication occurring in 6 out of 78 (8%) cases of fungal infection of the nervous system reported by Young et aL9 The identification of Candida albicans in the CSF of this patient was an unexpected finding after the VP shunt was inserted. Following 5 1 days of intravenous treatment with amphotericin B and flucytosine, the CSF became sterile even though the original shunt
Downloaded by [McMaster University] at 16:28 14 April 2016
Candida albicans ventriculitis
503
system was not removed. The patient appeared insertion of the shunt. In the case reported here clinically cured for 4 months. Tanglo and we had a negative mannan antigen in the CSF Yadev et a1.l1reported a similar experience in repeatedly for 17 days prior to re-shunting. being able to eradicate cryptococcal CSF In conclusion, the case presented here is infection in the presence of a shunt system. On another report of the occurrence of Candida the other hand, Gower et al.12 reported two albicans CNS infection in the absence of cases of primary Candida albicans shunt systemic candidiasis and immunosuppression. infection and reviewed the 10 previously The clinical course of the disease is insidious. reported cases showing that the mortality was Aggressive treatment with antimycotic ther25% and therapy involved the removal of the apy, intravenous and intrathecal, is required. shunt system. It is not clear whether the The associated hydrocephalus is better treated reappearance of Candida in the CSF of our by external ventricular drainage until the CSF patient was a recurrence or re-infection. In the is sterile, followed by shunting. Measurement absence of a primary focus of infection a re- of the mannan antigen is an additional parainfection seems unlikely. The recurrence of meter which will help the clinician to decide infection may be considered as a failure to treat that the infection is controlled and the shuntcandidal CSF infection in the presence of a ing procedure can be performed. shunt system. Treatment along the same principles as bacterial infection of the CSF in the Address for correspondence: Dr A. Jamjoom, presence of a shunt system is therefore advisDivision of Neurosurgery, King Khalid able.13 This involves removal of the system, University Hospital, PO Box 2925, Riyadh replacing it by external drainage, and when the 11461, Saudi Arabia. infection is totally eradicated the shunting system is reinserted. The mannan antigen is the main antigenic References polysaccharide component of the Candida cell 1 Lipton SA, Hickey WR, Morris JH et al. Candidal and can be detected in the serum of 92-100% infection of the central nervous system. Am J Med of cases with invasive candidia~is.'~Ikeda et 1984; 76~101-8. 2 Faix RG. Systemic Candida infections in infants in ~ 1 studied . ~ a case of cerebral granuloma and intensive care nurseries: high incidence of central meningitis caused by Candida albicans. They nervous system involvement. J Paediatr 1984; 105~616-22. monitored the mannan antigen and found it 3 Levy RM, Bredesen DE, Rosenblum ML. Neurologimore sensitive than the antibody. The latter cal manifestations of the acquired immune-deficiency can be high in normal people, low in patients syndrome (AIDS): experience at UCSF and review of literature. J Neurosurg 1985; 62:475-794. with depressed immune response and does not increase until a few weeks after i n f e ~ t i o n . ~ , ' ~4 Ikeda K, Yamashita J, Fujisawa H et al. Cerebral granuloma and meningitis caused by Candida albicans: In the case reported here, the mannan antigen useful monitoring of mannan antigen in cerebrospinal fluid. Neurosurgery 1990; 26:860-3. level was measured using the immunodif5 Ilgren EB, Westmorland D, Adam CBT et al. fusion method and therefore it was only Cerebellar mass caused by Candida species. J Neuropossible to define whether it was positive or surg 1984; 60:428-30. 6 Parker JC Jr, McCloskey JJ, Lee RS. The emergence of negative ( t 3 mg/l). A negative mannan candidosis: the dominant postmortem cerebral mycoantigen in the CSF correlated well with sis. Am J Clin Pathol 1978; 69:31-6. negative culture of Candida, indicating that 7 Haruda F, Bergman MA, Headings D. Unrecognized Candida brain abscess in infancy: two cases and a the antigen monitoring is accurate for evaluatreview of the literature. John Hopkins Med J 1980; ing the response to antifungal treatment," and 147~182-5. to support the decision of when to reinsert the 8 Parker JC Jr, McCloskey JJ, Lee RS. Human cerebral candidosis-a post-mortem evaluation of 19 patients. shunt system. It has been suggested by Ikeda et Hum Pathol 1981; 12:23-8. aL4 that normal concentration of mannan 9 Young RF, Gade G, Grinnel V. Surgical treatment for antigen in the CSF has to be confirmed fungal infections in the central nervous system. J Neurosurg 1985; 63:371-81. repeatedly for more than a week before the
504
Abdulhakim Jamjoom et al.
Downloaded by [McMaster University] at 16:28 14 April 2016
10 Tang LM. Ventriculoperitoneal shunt in crytococcal meningitis with hydrocephalus. Surg Neurol 1990; 33~314-19. 1 1 Yadev S, Perfect J, Friedman A. Successful treatment of cryptococcal ventriculoatrial shunt infection with systemic therapy alone. Neurosurgery 1988; 23:372-3. 12 Gower DJ, Crone K, Alexander E Jr et al. Candida albicans shunt infection: report of two cases. Neurosurgery 1986; 19:111-13. 13 Forward KR, Fewer HD, Stiver HG. Cerebrospinal
fluid shunt infections. A review of 35 infection in 32 patients. J Neurosurg 1983; 59:389-94. 14 Repentigney L, Reiss E. Current trends in immunodiagnosis of candidiasis and aspergillosis. Rev Infect Dis 1984; 6~301-12. 15 Meckstroth KL, Reiss E, Kellar JWet al. Detection of antibodies and antigenaemia in leukemic patient with candidiasis by enzyme-linked immunosorbent assay. J Infect Dis 1981; 144:24-32.
ISSN: 0268-8697 (Print) 1360-046X (Online) Journal homepage: http://www.tandfonline.com/loi/ibjn20
Ventriculitis and hydrocephalus caused by Candida albicans successfully treated by antimycotic therapy and cerebrospinal fluid shunting Abdulhakim Jamjoom, Zain Al-Abedeen Jamjoom, Saleh Al-Hedaithy, Abdulfatah Jamali, Naim-ur-Rahman & Tajuddin Malabarey To cite this article: Abdulhakim Jamjoom, Zain Al-Abedeen Jamjoom, Saleh Al-Hedaithy, Abdulfatah Jamali, Naim-ur-Rahman & Tajuddin Malabarey (1992) Ventriculitis and hydrocephalus caused by Candida albicans successfully treated by antimycotic therapy and cerebrospinal fluid shunting, British Journal of Neurosurgery, 6:5, 501-504, DOI: 10.3109/02688699208995043 To link to this article: http://dx.doi.org/10.3109/02688699208995043
Published online: 06 Jul 2009.
Submit your article to this journal
Article views: 20
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ibjn20 Download by: [McMaster University]
Date: 14 April 2016, At: 16:28
British Journal of Neurosurgely (1992) 6 , 501-504
SHORT REPORT
Downloaded by [McMaster University] at 16:28 14 April 2016
Ventriculitis and hydrocephalus caused by Candida albicans successfully treated by antimycotic therapy and cerebrospinal fluid shunting ABDULHAKIM JAMJOOM, ZAIN AL-ABEDEEN JAMJOOM, SALEH AL-HEDAITHY,* ABDULFATAH JAMALI, NAIM-UR-RAHMAN & TAJUDDIN MALABAREYt Division of Neurosurgely, and *Departments of Microbiology and fRadiology, King Khalid University Hospital, Riyadh, Saudi Arabia
Abstract A unique case of Candida albicans ventriculitis and hydrocephalus in the absence of any evidence of systemic candidiasis or immunosuppression is reported. Initial treatment with CSF shunting and intravenous antimycotic therapy appeared to have eradicated the infection. Recurrence occurred 5 months after discharge and this was treated by intravenous and intrathecal antimycotic therapy in addition to removal of the shunt system, external ventricular drainage and then replacement of the shunt. A concomitant pyogenic brain abscess responded to burrhole aspiration and antibiotics. The role of mannan antigen monitoring is discussed.
Key words: Candida albicans, hydrocephalus, mannan antigen, shunt infection, venm'culitis.
Introduction
Involvement of the central nervous system (CNS) with Candida occurs in 48-64% of the cases with dessiminated candidiasis'.* and it is not uncommon in the immunocompromised patient, occurring in 1.7% of cases with AIDS.3 Cerebral candidiasis in the absence of immunosuppression and without systemic manifestations is very We report a unique case of a previously healthy patient who developed Candida albicans ventriculitis and hydrocephalus. The infection and the recurrence were treated by cerebrospinal fluid (CSF) shunting and antimycotic therapy. In addition to stressing the rarity of isolated cerebral candidal infection in patients with normal immunity, the aim of this paper is to demonstrate the insidious clinical course of the disease, the management difficulties, and the
value of monitoring the mannan antigen during treatment.
Case history A 17-year-old female presented to our hospital with 3 months history of headaches, vomiting and dizziness. She was drowsy and apyrexial. She had bilateral papilloedema with normal visual acuity. Her gait was ataxic and had no clinical signs of meningism. C T showed evidence of hydrocephalus with no focal lesion or abnormal enhancement. An urgent right ventriculo-peritoneal (VP) shunt was performed. The ventricular CSF obtained at operation had a protein of 0.28 g/l, sugar of 1.7 mmol/l and WBC of 2 x 103/l. CSF microscopy and culture demonstrated Candida albicans. Fur-
50 l
Downloaded by [McMaster University] at 16:28 14 April 2016
502
Abdulhakim Jamjoom et al.
ther investigations showed that the patient had a negative blood culture, negative HIV status, normal serum immunoglobulins and a normal cell-mediated immunity response. Treatment was started with intravenous flucytosine (2 g/6 h) and amphotericin B (10 mglday). The dose of the latter was increased by 5 mg every week reaching 30 mg/day. Immediately postoperatively the patient became more alert; however, her headache and vomiting persisted. C T 3 days later showed a collapsed right lateral venticle while the left ventricle was still dilated. This was managed by catheterization of the left frontal horn and connecting the catheter to the pre-existing functioning right VP shunt. The antimycotic therapy was continued for 51 days even though the CSF had become sterile 21 days after starting treatment. She was discharged 59 days after admission. At the time she was alert, orientated with no deficits. The mannan antigen was negative in her CSF and blood and C T showed collapsed ventricles. Over the next 4 months the patient was reviewed as an out-patient twice. She remained clinically well. Five months after discharge, the patient was readmitted with 4 weeks history of recurrence of her previous symptoms. C T showed dilated right temporal horn with increased size of ventricles but no abnormal enhancement. The ventricular CSF had protein of 1.27 g/l, sugar of 1.9 mmol/l and WBC of 64 X 103/l. The CSF showed on microscopy and grew on culture Candida albicans again. In addition, the mannan antigen became positive in the CSF and blood. The patient was re-started on intravenous flucytosine and amphotericin B. Unfortunately, over the next 2 weeks, she deteriorated gradually, becoming slow, generally weak and developed dysconjugate gaze. The CSF continued to grow Candida albicans and the mannan antigen remained positive in the CSF and serum. Therefore, 20 days following readmission, the shunt tubes were removed and bilateral external ventricular drains were inserted. Treatment with flucytosine continued; however, amphotericin B was given intra-thecally (dose 0.25 mglday) and itraco-
nazole (100 mg/day) orally. Clinically the patient remained stable, drowsy with very little speech, anorexic and generally weak. Her recovery was complicated by a left frontal Staphylococcus aureus abscess which had originated from a thrombophlebitis in the left arm and which responded to treatment by burrhole aspiration, flucloxacillin and ceftrioxone. Following 21 days of external drainage, the CSF culture and mannan antigen had been negative on three occasions. The drains were then removed and bilateral VP shunts were inserted. Postoperatively, treatment with flucytosine and itraconazole was continued for a further 2 months. Her clinical recovery onward was good. The patient was able to communicate and mobilize. CT showed resolution of the frontal abscess and the ventricles were small. The patient was discharged 85 days after readmission. She was followed up for 6 months and during that time her dysconjugate gaze, ataxia and dysarthria improved slightly. In addition, the CSF mannan antigen remained negative.
Discussion Cerebral candidiasis has become the most prevalent cerebral mycosis diagnosed at autRecognized predisposing factors include: chemotherapy for cancer or transplanatation, immune deficiency syndromes, drug abuse, parenteral nutrition and intensive therapy treatment, gastrointestinal pathology and abdominal surgery, ageing, antibiotics and steroid therapy.*+’ The case presented here had none of the above risk factors and showed no evidence of extracranial disease. The patient had ventriculitis which caused hydrocephalus. The latter is a rare complication occurring in 6 out of 78 (8%) cases of fungal infection of the nervous system reported by Young et aL9 The identification of Candida albicans in the CSF of this patient was an unexpected finding after the VP shunt was inserted. Following 5 1 days of intravenous treatment with amphotericin B and flucytosine, the CSF became sterile even though the original shunt
Downloaded by [McMaster University] at 16:28 14 April 2016
Candida albicans ventriculitis
503
system was not removed. The patient appeared insertion of the shunt. In the case reported here clinically cured for 4 months. Tanglo and we had a negative mannan antigen in the CSF Yadev et a1.l1reported a similar experience in repeatedly for 17 days prior to re-shunting. being able to eradicate cryptococcal CSF In conclusion, the case presented here is infection in the presence of a shunt system. On another report of the occurrence of Candida the other hand, Gower et al.12 reported two albicans CNS infection in the absence of cases of primary Candida albicans shunt systemic candidiasis and immunosuppression. infection and reviewed the 10 previously The clinical course of the disease is insidious. reported cases showing that the mortality was Aggressive treatment with antimycotic ther25% and therapy involved the removal of the apy, intravenous and intrathecal, is required. shunt system. It is not clear whether the The associated hydrocephalus is better treated reappearance of Candida in the CSF of our by external ventricular drainage until the CSF patient was a recurrence or re-infection. In the is sterile, followed by shunting. Measurement absence of a primary focus of infection a re- of the mannan antigen is an additional parainfection seems unlikely. The recurrence of meter which will help the clinician to decide infection may be considered as a failure to treat that the infection is controlled and the shuntcandidal CSF infection in the presence of a ing procedure can be performed. shunt system. Treatment along the same principles as bacterial infection of the CSF in the Address for correspondence: Dr A. Jamjoom, presence of a shunt system is therefore advisDivision of Neurosurgery, King Khalid able.13 This involves removal of the system, University Hospital, PO Box 2925, Riyadh replacing it by external drainage, and when the 11461, Saudi Arabia. infection is totally eradicated the shunting system is reinserted. The mannan antigen is the main antigenic References polysaccharide component of the Candida cell 1 Lipton SA, Hickey WR, Morris JH et al. Candidal and can be detected in the serum of 92-100% infection of the central nervous system. Am J Med of cases with invasive candidia~is.'~Ikeda et 1984; 76~101-8. 2 Faix RG. Systemic Candida infections in infants in ~ 1 studied . ~ a case of cerebral granuloma and intensive care nurseries: high incidence of central meningitis caused by Candida albicans. They nervous system involvement. J Paediatr 1984; 105~616-22. monitored the mannan antigen and found it 3 Levy RM, Bredesen DE, Rosenblum ML. Neurologimore sensitive than the antibody. The latter cal manifestations of the acquired immune-deficiency can be high in normal people, low in patients syndrome (AIDS): experience at UCSF and review of literature. J Neurosurg 1985; 62:475-794. with depressed immune response and does not increase until a few weeks after i n f e ~ t i o n . ~ , ' ~4 Ikeda K, Yamashita J, Fujisawa H et al. Cerebral granuloma and meningitis caused by Candida albicans: In the case reported here, the mannan antigen useful monitoring of mannan antigen in cerebrospinal fluid. Neurosurgery 1990; 26:860-3. level was measured using the immunodif5 Ilgren EB, Westmorland D, Adam CBT et al. fusion method and therefore it was only Cerebellar mass caused by Candida species. J Neuropossible to define whether it was positive or surg 1984; 60:428-30. 6 Parker JC Jr, McCloskey JJ, Lee RS. The emergence of negative ( t 3 mg/l). A negative mannan candidosis: the dominant postmortem cerebral mycoantigen in the CSF correlated well with sis. Am J Clin Pathol 1978; 69:31-6. negative culture of Candida, indicating that 7 Haruda F, Bergman MA, Headings D. Unrecognized Candida brain abscess in infancy: two cases and a the antigen monitoring is accurate for evaluatreview of the literature. John Hopkins Med J 1980; ing the response to antifungal treatment," and 147~182-5. to support the decision of when to reinsert the 8 Parker JC Jr, McCloskey JJ, Lee RS. Human cerebral candidosis-a post-mortem evaluation of 19 patients. shunt system. It has been suggested by Ikeda et Hum Pathol 1981; 12:23-8. aL4 that normal concentration of mannan 9 Young RF, Gade G, Grinnel V. Surgical treatment for antigen in the CSF has to be confirmed fungal infections in the central nervous system. J Neurosurg 1985; 63:371-81. repeatedly for more than a week before the
504
Abdulhakim Jamjoom et al.
Downloaded by [McMaster University] at 16:28 14 April 2016
10 Tang LM. Ventriculoperitoneal shunt in crytococcal meningitis with hydrocephalus. Surg Neurol 1990; 33~314-19. 1 1 Yadev S, Perfect J, Friedman A. Successful treatment of cryptococcal ventriculoatrial shunt infection with systemic therapy alone. Neurosurgery 1988; 23:372-3. 12 Gower DJ, Crone K, Alexander E Jr et al. Candida albicans shunt infection: report of two cases. Neurosurgery 1986; 19:111-13. 13 Forward KR, Fewer HD, Stiver HG. Cerebrospinal
fluid shunt infections. A review of 35 infection in 32 patients. J Neurosurg 1983; 59:389-94. 14 Repentigney L, Reiss E. Current trends in immunodiagnosis of candidiasis and aspergillosis. Rev Infect Dis 1984; 6~301-12. 15 Meckstroth KL, Reiss E, Kellar JWet al. Detection of antibodies and antigenaemia in leukemic patient with candidiasis by enzyme-linked immunosorbent assay. J Infect Dis 1981; 144:24-32.
