MYCOSES 34,
59-61 (1991)
ACCEPTED: FEBRUARY6, 1991
CASEREPORT
African histoplasmosis in a Belgian AIDS patient Afrikanische Histoplasmose bei einem belgischen AIDS-Patienten V. Arendtl, J. Coremans-Pelseneer*,R. Gottlob3, T. Brill, W. Bujan-Bozal and P. Fondul Key words. Histoplasma duboisii, African histoplasmosis, AIDS. Schliisselworter. Histoplasma duboisii, afrikanische Histoplasmose, AIDS.
Summary. We describe an African histoplasmosis case in a 65-year-old Belgian living in Zaire for 46 years. Microscopic bone marrow examination showed Histoplasma. It was confirmed by cultures and hamster inoculation. Autopsy revealed a fungal dissemination by Histoplasma duboisii. Zusammenfassung. Der Fall einer afrikanischen Histoplasmose bei einem 65jahrigen Belgier wird beschrieben; der Patient lebte 46 Jahre in Zaire. Im Knochenmark wurde mikroskopisch Histoplasma nachgewiesen. Der Befund wurde kulturell und durch Anziichtung in Hamstern bestatigt. Die Autopsie ergab eine disseminierte Infektion mit Histoplasma duboisii. Case report The patient L. A., 65 year old, a Belgian evangelist, lived in Zaire since 1943. He married a Zairian woman from whom he had three children. His antecedents revealed a mastoiditis during infancy, an amoebic liver abscess in 1952, a bilateral hernia and an inguinal lymphadenitis operated in 1962, a typhoid fever in 1982, a bronchopneumonia with pleural reaction in 1987, a treated retinal detachment. Several attacks of malaria are noted. His HIV
I Hspital Universitaire St. Pierre, * Laboratoire de Parasitologie, U.L.B., and s Institut Jules Bordet, Bruxelles, Belgium.
Correspondence: Professor Dr Jacqueline Coremans-Pelseneer, Laboratoire de Parasitologie, Facultt de Medecine, 115 boulevard de Waterloo, B-1000 Bruxelles, Belgium.
seropositivity was known since 1987. He was hospitalized on May 27, 1989 at Brugmann hospital (Brussels) on his return from Zaire. He presented a weight loss of 10 kg, spiking fever for a month and an irregular diarrhea since 3 months. Treatment was Maloprim, 1 tablet per week. The patient was transfered to St. Pierre hospital (Brussels) on June 1, 1989. He had an oropharyngeal candidosis and small posterior axillary enlarged lymph nodes. Auscultation revealed some sibilant rhonchus at the right base of the lung, a moderate splenomegaly, a liver ptosis. Echography showed a homogeneous hepatomegaly. A right paracardiac infiltrate consistent with a bronchopneumonic focus was seen on the radiography. Laboratory examinations indicated a pancytopenia (Hb 7.4 g/dl, plateles 40,000/mm3, white cells 1,900; lymphopenia 7%). Different specimens were microbiologically negative, specially for Mycobacterium tuberculosis. Serology was negative for CMV, syphilis, B hepatitis and Toxoplasma, positive for malaria (IgG 1/400). During hospitalization the patient's general state deteriorated. He developed diffuse mesenteric hemorrhages and also at the left psoas level. Blood cultures and cultures from cerebrospinal fluid were negative for virus, bacteria, mycobacteria and fungi. At that time treatment included antituberculosis tritherapy, pefloxacine, AZT, metronidazole, aciclovir and a symptomatic treatment. Later the patient presented anal herpes and a cholestatic hepatitis probably due to medication. About June 20, a neutropenia and a thrombocytopenia (lO,OOO/ mm3) developed, followed by Acinetobacter and Candida parapsilosis septicemia treated by Tricarcillin-amikacine and amphotericin B respectively, starting from June 29. A third bone marrow punc-
60
V. ARENDTET AL.
Figure 1. Bone marrow smear. Small yeast cells inside of macrophages. (stain: May-Griinwald-Giernsa).
Figure 2. Spleen: Large yeast cells. (stain: Gornori’s rnethenamine silver).
tion performed on June 29 revealed small yeast cells (2-3 pm) in macrophages (Fig. 1). We diagnosed histoplasmosis. Another bone marrow punction realized on July 4, 1989, led to all cultures positive for Histoplasma showing microconidia (2-3 pm) and echinulated chlamydospores ( f 15 pm) on Sabouraud glucose medium and on ten time diluted Sabouraud glucose medium. Several yeast colonies were obtained on blood medium. One blood culture was also positive for Histoplasma. The patient died on July 5, 1989.
In these cases, Graybill [2] noticed that the most contributive specimen is the bone marrow. It is important to remind that the epidemiology of African histoplasmosis is unknown. H. duboisii was never isolated from the environment [3]. The mode of invasion of the fungus into the human body is therefore unknown. African histoplasmosis is only known in its symptomatic form which differs completely from classical histoplasmosis, mainly by usual absence of pulmonary lesions, except if generalization occurs. The main localizations in the 212 African histoplasmosis cases described are the skin, lymph nodes, bones and the viscera, dissemination occurring only in about 15% of the cases. T o our knowledge, we describe [4], the first case of African histoplasmosis associated with AIDS. This one is the second found in Belgium. One of us, R. Gottlob, found two other cases by reexamining histological autopsy findings. Both were observed in Belgians who stayed for many years in Zaire. A fifth case was observed in Zaire in 1988 [5, 61 in a Zairian. It is important to point out that in these five cases dissemination seemed to occur directly.
A u topsy At autopsy, histological examination displayed small and large yeast cells (8-13 pm) (Fig. 2) with a thick wall typical for Histoplasma duboisii [ 11, the agent of African histoplasmosis. Invaded organs were the liver, the spleen, the lymph glands, bone marrow, the lungs. Hyphae associated with blastospores were found at lymph glands, splenic, mesocolic and pulmonary levels.
Laboratory results Liver, spleen, lung and ganglionar pieces were sampled aseptically at autopsy. H . duboisii was cultivated from the spleen, Candida albicans and C. parapsilosis were cultivated from all four samples. The interperitoneal inoculation of hamsters confirmed H. duboisii diagnosis.
Discussion In USA, the relationship between histoplasmosis due to Histoplasma capsulatum and AIDS is well documented. The US authors agree on a percentage of 4 to 10% of histoplasmosis occurring in H I V + patients. This mycosis seems to be the reactivation of an old infection rather than a primary infection.
Conclusion As it seems likely that an asymptomatic form of African histoplasmosis exists, new epidemiological studies should be done in Central Africa, and the African histoplasmosis cases have to be reconsidered. If more African histoplasmosis cases associated with AIDS would be observed this diagnosis has to be reconsidered systematically in African or resident patients in Africa. Nevertheless the number of cases of African histoplasmosis obviously did not rise after the eighties in Africa, as it is the case for cryp tococcosis. mycoses 34, 59-6 1 ( 1991)
AFRICAN HISTOPLASMOSIS I N A BELGIANAIDS
PATIENT
61
References 1 Vanbreuseghem, R. ( 1 953) Histoplasma duboisii and African histoplasmosis. Mycologia 45, 803-8 16.
2 Graybill, J. R. (1988) Histoplasmosis and AIDS. J. Inf:Dis. 158,623-626. 3 Marjolet, M., Maiga, Y. I. & Morel, D. (1987) Essais d’isolements de souches d’Histoplasma capsulatum de sols du Mali. Interkt de la recherche d’exo-antigtnes. Bull. SOC. Fr. Mycol. Mkd. 16, 367-372. 4 DeprC, G., Coremans-Pelseneer,J., Peeters, P., Rickaert, F., Struelens, M. & Serruys, E. (1987) Histoplasmose africaine disseminke associee i un syndrome d’immunodkficience acquise. Bull. SOC.Fr. Mycol. M a . 16, 75-80. 5 Lannoie, L. (1990) personal communication. 6 Marcher, A. M., De Vinatea, M. L., Tuur, S. M. & Col, P. A. (1988) AIDS and mycosis in Infections Disease Clinics of North America. Philadelphia: Saunders, pp. 83 1-832. I UACUOMOLENtE BlOS-
J. F. Ryley, Macclesfield, UK (Ed.)
Chemotherapy of Fungal Diseases 1990.XXV, 558 pp. 72 figs. 68 tabs. (Handbook of Experimental Pharmacology, Vol. 96) Hardcover DM 480,- ISBN 3-540-52232-8 This handbook charts the processes involved in the discovery, development and final clinical utilization of a new drug for hngal diseases. Its purpose is to help the specialist involved at just one stage appreciate the nkcessary contributions by the many others involved in the complex process of drug discovery and development. Five groups of readers will benefit from this volume. The experimentalistwill find stimulation and provocation concerning approaches to drug discovery and screening. The expert responsible for the evaluation of the safety of drugs will find background information to help deliniate the biochemical, pharmacokineticand toxicologicalproperties of candidate compounds. The clinician will find an appreciation of the effort necessary to develop new agents. The academic will find an overview of the non-academic aspects; and the manager will see the urgent needs and opportunities which the field of antifungal chemotherapy presents to the pharmaceuticalindustry. Heidelberger Platz 3. W-loo0 Berlin 33, F. R.Qermany 0 175 Fifth Ave., NewYork, NY 10010, USA 0 8 Alexandra Rd.. London SW19 7JZ. England 0 26, rue des Carmes. F-75005Paris 37-3. Hongo3-chome.Bunkyo-ku. Tokyoll3,bpan 0 Citicorp Centre, Room 1603. 18 Whitfield Road, Causeway Bay. Hone Kong 0 Avinguda Diagonal, 468-4’C, E-08006 Barcelona
mycoses 34, 59-6 1 ( 199 1)
I
59-61 (1991)
ACCEPTED: FEBRUARY6, 1991
CASEREPORT
African histoplasmosis in a Belgian AIDS patient Afrikanische Histoplasmose bei einem belgischen AIDS-Patienten V. Arendtl, J. Coremans-Pelseneer*,R. Gottlob3, T. Brill, W. Bujan-Bozal and P. Fondul Key words. Histoplasma duboisii, African histoplasmosis, AIDS. Schliisselworter. Histoplasma duboisii, afrikanische Histoplasmose, AIDS.
Summary. We describe an African histoplasmosis case in a 65-year-old Belgian living in Zaire for 46 years. Microscopic bone marrow examination showed Histoplasma. It was confirmed by cultures and hamster inoculation. Autopsy revealed a fungal dissemination by Histoplasma duboisii. Zusammenfassung. Der Fall einer afrikanischen Histoplasmose bei einem 65jahrigen Belgier wird beschrieben; der Patient lebte 46 Jahre in Zaire. Im Knochenmark wurde mikroskopisch Histoplasma nachgewiesen. Der Befund wurde kulturell und durch Anziichtung in Hamstern bestatigt. Die Autopsie ergab eine disseminierte Infektion mit Histoplasma duboisii. Case report The patient L. A., 65 year old, a Belgian evangelist, lived in Zaire since 1943. He married a Zairian woman from whom he had three children. His antecedents revealed a mastoiditis during infancy, an amoebic liver abscess in 1952, a bilateral hernia and an inguinal lymphadenitis operated in 1962, a typhoid fever in 1982, a bronchopneumonia with pleural reaction in 1987, a treated retinal detachment. Several attacks of malaria are noted. His HIV
I Hspital Universitaire St. Pierre, * Laboratoire de Parasitologie, U.L.B., and s Institut Jules Bordet, Bruxelles, Belgium.
Correspondence: Professor Dr Jacqueline Coremans-Pelseneer, Laboratoire de Parasitologie, Facultt de Medecine, 115 boulevard de Waterloo, B-1000 Bruxelles, Belgium.
seropositivity was known since 1987. He was hospitalized on May 27, 1989 at Brugmann hospital (Brussels) on his return from Zaire. He presented a weight loss of 10 kg, spiking fever for a month and an irregular diarrhea since 3 months. Treatment was Maloprim, 1 tablet per week. The patient was transfered to St. Pierre hospital (Brussels) on June 1, 1989. He had an oropharyngeal candidosis and small posterior axillary enlarged lymph nodes. Auscultation revealed some sibilant rhonchus at the right base of the lung, a moderate splenomegaly, a liver ptosis. Echography showed a homogeneous hepatomegaly. A right paracardiac infiltrate consistent with a bronchopneumonic focus was seen on the radiography. Laboratory examinations indicated a pancytopenia (Hb 7.4 g/dl, plateles 40,000/mm3, white cells 1,900; lymphopenia 7%). Different specimens were microbiologically negative, specially for Mycobacterium tuberculosis. Serology was negative for CMV, syphilis, B hepatitis and Toxoplasma, positive for malaria (IgG 1/400). During hospitalization the patient's general state deteriorated. He developed diffuse mesenteric hemorrhages and also at the left psoas level. Blood cultures and cultures from cerebrospinal fluid were negative for virus, bacteria, mycobacteria and fungi. At that time treatment included antituberculosis tritherapy, pefloxacine, AZT, metronidazole, aciclovir and a symptomatic treatment. Later the patient presented anal herpes and a cholestatic hepatitis probably due to medication. About June 20, a neutropenia and a thrombocytopenia (lO,OOO/ mm3) developed, followed by Acinetobacter and Candida parapsilosis septicemia treated by Tricarcillin-amikacine and amphotericin B respectively, starting from June 29. A third bone marrow punc-
60
V. ARENDTET AL.
Figure 1. Bone marrow smear. Small yeast cells inside of macrophages. (stain: May-Griinwald-Giernsa).
Figure 2. Spleen: Large yeast cells. (stain: Gornori’s rnethenamine silver).
tion performed on June 29 revealed small yeast cells (2-3 pm) in macrophages (Fig. 1). We diagnosed histoplasmosis. Another bone marrow punction realized on July 4, 1989, led to all cultures positive for Histoplasma showing microconidia (2-3 pm) and echinulated chlamydospores ( f 15 pm) on Sabouraud glucose medium and on ten time diluted Sabouraud glucose medium. Several yeast colonies were obtained on blood medium. One blood culture was also positive for Histoplasma. The patient died on July 5, 1989.
In these cases, Graybill [2] noticed that the most contributive specimen is the bone marrow. It is important to remind that the epidemiology of African histoplasmosis is unknown. H. duboisii was never isolated from the environment [3]. The mode of invasion of the fungus into the human body is therefore unknown. African histoplasmosis is only known in its symptomatic form which differs completely from classical histoplasmosis, mainly by usual absence of pulmonary lesions, except if generalization occurs. The main localizations in the 212 African histoplasmosis cases described are the skin, lymph nodes, bones and the viscera, dissemination occurring only in about 15% of the cases. T o our knowledge, we describe [4], the first case of African histoplasmosis associated with AIDS. This one is the second found in Belgium. One of us, R. Gottlob, found two other cases by reexamining histological autopsy findings. Both were observed in Belgians who stayed for many years in Zaire. A fifth case was observed in Zaire in 1988 [5, 61 in a Zairian. It is important to point out that in these five cases dissemination seemed to occur directly.
A u topsy At autopsy, histological examination displayed small and large yeast cells (8-13 pm) (Fig. 2) with a thick wall typical for Histoplasma duboisii [ 11, the agent of African histoplasmosis. Invaded organs were the liver, the spleen, the lymph glands, bone marrow, the lungs. Hyphae associated with blastospores were found at lymph glands, splenic, mesocolic and pulmonary levels.
Laboratory results Liver, spleen, lung and ganglionar pieces were sampled aseptically at autopsy. H . duboisii was cultivated from the spleen, Candida albicans and C. parapsilosis were cultivated from all four samples. The interperitoneal inoculation of hamsters confirmed H. duboisii diagnosis.
Discussion In USA, the relationship between histoplasmosis due to Histoplasma capsulatum and AIDS is well documented. The US authors agree on a percentage of 4 to 10% of histoplasmosis occurring in H I V + patients. This mycosis seems to be the reactivation of an old infection rather than a primary infection.
Conclusion As it seems likely that an asymptomatic form of African histoplasmosis exists, new epidemiological studies should be done in Central Africa, and the African histoplasmosis cases have to be reconsidered. If more African histoplasmosis cases associated with AIDS would be observed this diagnosis has to be reconsidered systematically in African or resident patients in Africa. Nevertheless the number of cases of African histoplasmosis obviously did not rise after the eighties in Africa, as it is the case for cryp tococcosis. mycoses 34, 59-6 1 ( 1991)
AFRICAN HISTOPLASMOSIS I N A BELGIANAIDS
PATIENT
61
References 1 Vanbreuseghem, R. ( 1 953) Histoplasma duboisii and African histoplasmosis. Mycologia 45, 803-8 16.
2 Graybill, J. R. (1988) Histoplasmosis and AIDS. J. Inf:Dis. 158,623-626. 3 Marjolet, M., Maiga, Y. I. & Morel, D. (1987) Essais d’isolements de souches d’Histoplasma capsulatum de sols du Mali. Interkt de la recherche d’exo-antigtnes. Bull. SOC. Fr. Mycol. Mkd. 16, 367-372. 4 DeprC, G., Coremans-Pelseneer,J., Peeters, P., Rickaert, F., Struelens, M. & Serruys, E. (1987) Histoplasmose africaine disseminke associee i un syndrome d’immunodkficience acquise. Bull. SOC.Fr. Mycol. M a . 16, 75-80. 5 Lannoie, L. (1990) personal communication. 6 Marcher, A. M., De Vinatea, M. L., Tuur, S. M. & Col, P. A. (1988) AIDS and mycosis in Infections Disease Clinics of North America. Philadelphia: Saunders, pp. 83 1-832. I UACUOMOLENtE BlOS-
J. F. Ryley, Macclesfield, UK (Ed.)
Chemotherapy of Fungal Diseases 1990.XXV, 558 pp. 72 figs. 68 tabs. (Handbook of Experimental Pharmacology, Vol. 96) Hardcover DM 480,- ISBN 3-540-52232-8 This handbook charts the processes involved in the discovery, development and final clinical utilization of a new drug for hngal diseases. Its purpose is to help the specialist involved at just one stage appreciate the nkcessary contributions by the many others involved in the complex process of drug discovery and development. Five groups of readers will benefit from this volume. The experimentalistwill find stimulation and provocation concerning approaches to drug discovery and screening. The expert responsible for the evaluation of the safety of drugs will find background information to help deliniate the biochemical, pharmacokineticand toxicologicalproperties of candidate compounds. The clinician will find an appreciation of the effort necessary to develop new agents. The academic will find an overview of the non-academic aspects; and the manager will see the urgent needs and opportunities which the field of antifungal chemotherapy presents to the pharmaceuticalindustry. Heidelberger Platz 3. W-loo0 Berlin 33, F. R.Qermany 0 175 Fifth Ave., NewYork, NY 10010, USA 0 8 Alexandra Rd.. London SW19 7JZ. England 0 26, rue des Carmes. F-75005Paris 37-3. Hongo3-chome.Bunkyo-ku. Tokyoll3,bpan 0 Citicorp Centre, Room 1603. 18 Whitfield Road, Causeway Bay. Hone Kong 0 Avinguda Diagonal, 468-4’C, E-08006 Barcelona
mycoses 34, 59-6 1 ( 199 1)
I
