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Cryptococcal meningitis in Cairo, Egypt: report of five cases
410 TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE (1995) 89, 410
admission. Patient no. 1 was also comatose;he initially responded to therapy but relapsed and died after 1 month. The Table provides additional information on the cases. Laboratory diagnosis of cryptococcal meningitis depends primarily on CSF microscopy, culture and latex agglutination tests. Culture of an adequate quantity of CSF is the most sensitive definitive diagnosis. Direct microscopy of CSF using India ink staining, compared to culture, has 55-60% sensitivity with 100% specificity, while antigen detection assayssuch as the latex agglutination test can increase sensitivity to as high as 92% with equally high specificity (MERZ & ROBERTS, 1991). The clinical management of cryptococcal meningitis involves prolonged therapy (minimum 4-6 weeks), using amphotericin B often combined with 5-flucytosine. Recent clinical trials have demonstrated the value of the new triazole antifungal agent, fluconazole (SUGAR et al., 1990). The mortality rate has been previously reported to be 25-30% for those patients treated for cryptococcal meningitis (SUGAR et al., 1990). Poor prognostic indicators include a low CSF glucose level, fewer than 20 leucocytes/mm3, and CSF cryptococcal antigen titre >1:1054 (DIAMOND & BENNETT, 1974). The single most important predictor of mortality is the mental status of the patient on admission; neither of the 2 patients in our series who survived (nos. 4 and 5) was comatose on admission, though one (no. 5) was drowsy. In conclusion, consideration must be given to cryptococcosisas a potential aetiology of subacute meningitis in Egypt, even though it appears to be relatively uncommon. Diagnostic evaluation using India ink staining is a technically simple and inexpensive method when culture or antigen detection is not available. Cases of documented cryptococcosis should have a thorough evaluation for potential predisposing risk factors including HIV serology, even in regions with a documented low prevalence of HIV infection.
1Short Report 1 Cryptococcal meningitis in Cairo, Egypt: report of five cases A. Solimanl, D. Tribblel, M. Loui&, Y. Sultanz, A. Salibl, R. Hibbd and N. Girgisl ‘US Naval Medical Research Unit No. 3, Cairo, Egypt; 2Abbassia Fever Hospital, Ministry of Health, Cairo, Egypt Keywords: Cvyptococcus,cryptococcalmeningitis, casereports,
Egypt The diagnosis of subacute or chronic meningitis can be extremely challenging, for many reasons.The most commonly reported infectious aetiology is Mycobacterium tuberculosis, followed by Cryptococcus neoformans. Cryptococcal infection accounts for the most common form of fungal meningitis in developed countries as well as being a common illness defining patients with acquired immune deficiency syndrome. The encapsulated yeast-like fungus, C. neoformans, is naturally distributed in association with avian excreta (usually of pigeons) and soil, most commonly in temperate climates (LEVITZ, 1991). In 1989-1992, 305 patients with subacute meningitis were admitted to the Abbassia Fever Hospital, Cairo, Egypt. Diagnostic examination included cerebrospinal fluid (CSF) cell count, differential cell count, glucose and protein concentrations, Gram staining, bacterial culture, AFB (Kinyoun/fluorochrome) stain, mycobacterial culture, India ink staining, use of selective culture media for Cryptococcus spp. (esculin-based and Staib agar), and a latex agglutination test for cryptococcal antigen. Among the 305 patients, 108 (35.4%) had CSF culture-positive tuberculous meningitis, 192 (62.9%) had a negative diagnostic evaluation and were managed as presumptive tuberculous meningitis, and 5 (1.6%) had cryptococcal meningitis. The mortality rates in tuberculous, unknown/presumptive tuberculous, and cryptococcal meningitis were 55%, 63%, and 60% respectively. Isolates of C. neoformans were identified as serotype A at the National Institutes of Health (USA). Cryptococcosis is a relatively rare cause of non-acute
Acknowledgement This research was supported by the Naval Medical Research and Development Command, NMC, NCR, Bethesda, Maryland, USA, Work Unit no. OOlOl.EMX.3405. The opinions and assertionscontained herein are the private onesof the authors and are not to be construed as official or as reflecting the views of the US Navy Department, US Department of Defense,the US Government, or the Egyptian Ministry of Health.
Table. Cryptococcal meningitis case descriptions Case no. :
Age (years)
Sex
24 30 i: 11
E: Female Male Male
Duration of Extra-CNS disease illness (d) 307 3: 10
None None SkinLU&nhnn
Cerebrgfj;$
fluid ProteinC (mg%) h-4-%)
WBCa ‘% 220 1:oo
i ;: 16
E 27: 108
+ + +
Late2 titre
Culture
128 <32 32 ~32
+ +
%eucoc tes/mm3 cNormaYrange 74-l 10 mg%. pormal range 15-45 mg /a. Latex agglutination reciprocal titre; values <32 considered asnegative.
mellitus, respectively) and both presented severely ill and comatose, and died within the first week after hospital
References Diamond, R. D. & Bennett, J. E. (1974). Prognostic factors in cryptococcal meningitis. Annals of Internal Medicine, 80, 176-181. Levitz, S. M. (1991). The ecology of Cyptococcus neoformans and the epidemiology of cryptococcosis. Reviews of Infectious Diseases, 13,1163-1169. Merz, W. G. & Roberts, G. D. (1991). Detection and recovery of fungi from clinical specimens. In: Manual of Medical Microbiology, Balows, A., Hausler, W. J., Herrmann, K. L., Isenberg, H. D. & Shadomy, H. J. (editors), 5th edition. Washington, DC: ASM Press, pp. 588-600. Sugar, A. M., Stern, J. J. & DuPont, B. (1990). Overview: treatment of cryptococcal meningitis. Reviews of Infectious Diseases,12,338-348.
Address for correspondence and offprint requests: Research Publication Branch, US Naval Medical Research Unit No. 3, PSC 452, Box 5000, Code (lOlF), FPO, AE 09835-0007.
Received 17 November 1994; revised 3 January acceptedfor publication 3January I995
meningitis in Egypt, but it is associatedwith a high mortality rate in people with non-acute meningitis. Three patients (nos. 1, 2 and 3) died, 2 of them (nos. 2 and 3) within the first 24-48 h of initiating therapy with amphotericin B, 0.3 mglkgid intravenously plus flucytosine 100 mgikgid orally. Cryptococcal infection is frequently an opportunistic infection affecting patients with defects in cell-mediated immunity or other associatedillnesses (LEVITZ, 1991).Two of the patients in this series(nos. 2 and 3) had documented risk factors for cryptococcosis (human immunodeficiency virus (HIV) infection and diabetes
1995;
admission. Patient no. 1 was also comatose;he initially responded to therapy but relapsed and died after 1 month. The Table provides additional information on the cases. Laboratory diagnosis of cryptococcal meningitis depends primarily on CSF microscopy, culture and latex agglutination tests. Culture of an adequate quantity of CSF is the most sensitive definitive diagnosis. Direct microscopy of CSF using India ink staining, compared to culture, has 55-60% sensitivity with 100% specificity, while antigen detection assayssuch as the latex agglutination test can increase sensitivity to as high as 92% with equally high specificity (MERZ & ROBERTS, 1991). The clinical management of cryptococcal meningitis involves prolonged therapy (minimum 4-6 weeks), using amphotericin B often combined with 5-flucytosine. Recent clinical trials have demonstrated the value of the new triazole antifungal agent, fluconazole (SUGAR et al., 1990). The mortality rate has been previously reported to be 25-30% for those patients treated for cryptococcal meningitis (SUGAR et al., 1990). Poor prognostic indicators include a low CSF glucose level, fewer than 20 leucocytes/mm3, and CSF cryptococcal antigen titre >1:1054 (DIAMOND & BENNETT, 1974). The single most important predictor of mortality is the mental status of the patient on admission; neither of the 2 patients in our series who survived (nos. 4 and 5) was comatose on admission, though one (no. 5) was drowsy. In conclusion, consideration must be given to cryptococcosisas a potential aetiology of subacute meningitis in Egypt, even though it appears to be relatively uncommon. Diagnostic evaluation using India ink staining is a technically simple and inexpensive method when culture or antigen detection is not available. Cases of documented cryptococcosis should have a thorough evaluation for potential predisposing risk factors including HIV serology, even in regions with a documented low prevalence of HIV infection.
1Short Report 1 Cryptococcal meningitis in Cairo, Egypt: report of five cases A. Solimanl, D. Tribblel, M. Loui&, Y. Sultanz, A. Salibl, R. Hibbd and N. Girgisl ‘US Naval Medical Research Unit No. 3, Cairo, Egypt; 2Abbassia Fever Hospital, Ministry of Health, Cairo, Egypt Keywords: Cvyptococcus,cryptococcalmeningitis, casereports,
Egypt The diagnosis of subacute or chronic meningitis can be extremely challenging, for many reasons.The most commonly reported infectious aetiology is Mycobacterium tuberculosis, followed by Cryptococcus neoformans. Cryptococcal infection accounts for the most common form of fungal meningitis in developed countries as well as being a common illness defining patients with acquired immune deficiency syndrome. The encapsulated yeast-like fungus, C. neoformans, is naturally distributed in association with avian excreta (usually of pigeons) and soil, most commonly in temperate climates (LEVITZ, 1991). In 1989-1992, 305 patients with subacute meningitis were admitted to the Abbassia Fever Hospital, Cairo, Egypt. Diagnostic examination included cerebrospinal fluid (CSF) cell count, differential cell count, glucose and protein concentrations, Gram staining, bacterial culture, AFB (Kinyoun/fluorochrome) stain, mycobacterial culture, India ink staining, use of selective culture media for Cryptococcus spp. (esculin-based and Staib agar), and a latex agglutination test for cryptococcal antigen. Among the 305 patients, 108 (35.4%) had CSF culture-positive tuberculous meningitis, 192 (62.9%) had a negative diagnostic evaluation and were managed as presumptive tuberculous meningitis, and 5 (1.6%) had cryptococcal meningitis. The mortality rates in tuberculous, unknown/presumptive tuberculous, and cryptococcal meningitis were 55%, 63%, and 60% respectively. Isolates of C. neoformans were identified as serotype A at the National Institutes of Health (USA). Cryptococcosis is a relatively rare cause of non-acute
Acknowledgement This research was supported by the Naval Medical Research and Development Command, NMC, NCR, Bethesda, Maryland, USA, Work Unit no. OOlOl.EMX.3405. The opinions and assertionscontained herein are the private onesof the authors and are not to be construed as official or as reflecting the views of the US Navy Department, US Department of Defense,the US Government, or the Egyptian Ministry of Health.
Table. Cryptococcal meningitis case descriptions Case no. :
Age (years)
Sex
24 30 i: 11
E: Female Male Male
Duration of Extra-CNS disease illness (d) 307 3: 10
None None SkinLU&nhnn
Cerebrgfj;$
fluid ProteinC (mg%) h-4-%)
WBCa ‘% 220 1:oo
i ;: 16
E 27: 108
+ + +
Late2 titre
Culture
128 <32 32 ~32
+ +
%eucoc tes/mm3 cNormaYrange 74-l 10 mg%. pormal range 15-45 mg /a. Latex agglutination reciprocal titre; values <32 considered asnegative.
mellitus, respectively) and both presented severely ill and comatose, and died within the first week after hospital
References Diamond, R. D. & Bennett, J. E. (1974). Prognostic factors in cryptococcal meningitis. Annals of Internal Medicine, 80, 176-181. Levitz, S. M. (1991). The ecology of Cyptococcus neoformans and the epidemiology of cryptococcosis. Reviews of Infectious Diseases, 13,1163-1169. Merz, W. G. & Roberts, G. D. (1991). Detection and recovery of fungi from clinical specimens. In: Manual of Medical Microbiology, Balows, A., Hausler, W. J., Herrmann, K. L., Isenberg, H. D. & Shadomy, H. J. (editors), 5th edition. Washington, DC: ASM Press, pp. 588-600. Sugar, A. M., Stern, J. J. & DuPont, B. (1990). Overview: treatment of cryptococcal meningitis. Reviews of Infectious Diseases,12,338-348.
Address for correspondence and offprint requests: Research Publication Branch, US Naval Medical Research Unit No. 3, PSC 452, Box 5000, Code (lOlF), FPO, AE 09835-0007.
Received 17 November 1994; revised 3 January acceptedfor publication 3January I995
meningitis in Egypt, but it is associatedwith a high mortality rate in people with non-acute meningitis. Three patients (nos. 1, 2 and 3) died, 2 of them (nos. 2 and 3) within the first 24-48 h of initiating therapy with amphotericin B, 0.3 mglkgid intravenously plus flucytosine 100 mgikgid orally. Cryptococcal infection is frequently an opportunistic infection affecting patients with defects in cell-mediated immunity or other associatedillnesses (LEVITZ, 1991).Two of the patients in this series(nos. 2 and 3) had documented risk factors for cryptococcosis (human immunodeficiency virus (HIV) infection and diabetes
1995;