Diagnostic considerations on visceral leishmaniasis. Two case reports
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Diagnostic considerations on visceral leishmaniasis. Two case reports
Le Infezioni in Medicina, n. 3, 176-178, 2002 Casi clinici Case reports Diagnostic considerations on visceral leishmaniasis. Two case reports Considerazioni diagnostiche sulla Leishmaniosi viscerale: descrizione di due casi clinici 1 1 2 Maria Bruna Pasticci , Rita Papili , Francesco Menichetti , Stelvio Ballanti3, Letizia Ottaviani3, Antonio Tabilio3, Giuliano Stagni1 1 Dipartimento Medicina Sperimentale e Scienze Biochimiche, Sezione Clinica di Malattie Infettive, Università degli Studi di Perugia, Perugia 2 Unità Operativa Malattie Infettive, Presidio Ospedaliero Cisanello, Azienda Ospedaliera Pisana, Pisa 3 Dipartimento di Medicina Clinica e Sperimentale, Sezione di Ematologia, Università degli Studi di Perugia, Perugia ■ INTRODUCTION 450 UI/l), AST 61 UI/l (<46 UI/l). Other parameters resulted within normal limits. The percentage of CD4 and CD8 lymphocytes was normal; HIV serology tested negative. A repeated bone biopsy was consistent with midollary iperplasia secondary to ipersplenism. Mean time anti-Leishmania antibodies (Indirect Fluorescent Assay) resulted positive with a title of 1:2560 and the patient was started on liposomial amphotericin B (AmBisome) 3 mg/kg/die. Before treatment a new bone marrow aspirate was sent for Leishmania at the Parasitology Laboratory, Istituto Superiore Sanità in Rome. Both microscopy and culture were positive. Within 48 hrs from treatment the patient became afebrile, amphotericin was continued for a total of 10 days [1]. On discharge the patient was well, abnormal laboratory tests had improved and the spleen size was reduced of 3.5 cm. The patient was seen one month later in good condition, hematologic parameters showed RBCs 4.100.000/mmc, Hb 10.4 g/dl, WBCs 3.400/mmc, platelets 237.000/mmc, normal ESR. The clinical picture of Visceral leishmaniasis (VL) is variable and often indistinguishable from that of other diseases including hemathologic disorders. In endemic areas the presence of fever, weight loss, massive splenomegaly, hepatomegaly, anemia, leukopenia and hypergammaglobulinemia is highly suggestive of VL and should prompt specific investigations. The Authors describe two cases of VL in immunocompetent patients. Case no. 1. A 23-year-old female from Sicily was admitted at the Hemathology Department of Perugia University because of 2 months history of fever, anemia, leukopenia, low platelet count and splenomegaly. Since childhood the patient reported repeated episodes of oral candidiasis, and chronic onycomycosis. During the past month she had been investigated extensively including a bone biopsy without a definitive diagnosis. When her primary health care physician suggested a diagnostic splenectomy she signed out and was seen for the first time at Perugia University. On hospitalization the patient was febrile, the temperature was 39°C, had onycomycosis of the second finger of the left hand, oral candidiasis, diffuse microlimphoadenopaty and splenomegaly. The laboratory tests showed RBCs 2.800.000/mmc, Hb 6.9 g/dl, WBCs 1.100 mmc, platelets 76.000/mmc, ERS 52, γ-globulin 1770 mg/dl (751-1560 mg/dl), LDH 1439 UI/l (230- Case no. 2. A 64-year-old female from Calabria was admitted at the Infectious Disease Institute of Perugia because of suspected tuberculosis. Three months before hospitalization the patient reported one week of fever, with low grade temperature, followed by a discreet petecchial eruption on the left leg. At that time laboratory tests revealed Hb 10.2 g/dl, platelets 72.000/mmc, γglobulin 4990 mg/dl. The abdominal ultra- 176 2002 stration of amastigotes within macrofages or close to disrupted cells in bone marrow, spleen, liver, lymphonode and other tissue or upon culture (promastigotes). Microscopy is difficult considering the size of the parasite itself. Culture requires specific techniques and media, it is 1 log more sensitive than smears. In general, serology is not reported to be a very useful test in both visceral and cutaneous leishmaniasis as it may give false positive as well as false negative results [1]. In these two patients anti-Leishmania antibodies were obtained late during hospital admission, and were not considered significant until the diagnosis of VL was confirmed by microscopic observation. In both patients Indirect Fluorescent Assay tested positive with a title well above the cut-off (1:80). Data from the Reference Laboratory for Leishmania at the Istituto Superiore di Sanità in Rome indicate sensitivity rates of serology close to 100% and specificity of 98% in immunocompetent patients [5]. In the literature similar values are reported for ELISA. In general, sensitivity drops to about 60% with both tests when immunocompromised patients and recepient of organ transplants are examined [5]. It must be reminded that the same patient population is more susceptible to symptomatic visceral leishmaniasis [6-9]. Serology is less invasive than bone marrow aspirate or biopsy, and it may perform in a more reproducible fashion in laboratories with less expertness of parasitic diseases. Positive serology can be used also to monitor the response to therapy and to detect relapse after treatment. Liposomial amphotericin B has been shown to be an effective treatment for visceral leishmaniasis, it has been recently approved by the Food and Drug Administration with this indication. In immunocompetent patients the total dose recommended is 21 mg/Kg given on 7 days over 21 day period [9, 10]. We used in one case 18 mg/Kg, while in the other were infused 30 mg/kg, in both cases a prompt clearance of symptoms was recorded along with no side effects. sound documented hepatomegaly with splenomegaly (18 cm of diameter). The bone marrow histology was consistent with mild increase of plasmacellular component with normal cells of politopic origin. During the first admission a diagnostic splenectomy, along with liver and abdominal lymphonode biopsy, was performed. The pathologist reported infiltration of lymphomonocytes with normal characteristic in all the specimens. Within the spleen was also described a wide area of necrosis with caseosis. At that point the patient was referred to the Infectious Disease Institute of Perugia for suspected tuberculosis. On admission the patient was afebrile, had mild hepatomegaly. Laboratory test showed: ESR 95, RBCs 4.080.000/mmc, WBCs 9.300/mmc, Hb 10.7 g/dl, platelets 371.000/mmc, total proteins 10.5 g/dl, albumin 3.3 g/dl, γ-globulin 5160 mg/dl, AST 97 UI/l (<46 UI/l), ALT 67 UI/l (<46 UI/l), γGGT 78 UI/l (<51 UI/l), CD4 18%, CD8 12.0%; anti-HIV antibodies were negative. Anti-Leishmania antibodies (IFA) tested positive with a title of 1:20480. A new evaluation of the previous spleen and liver preparates for the presence of amastigotes of Leishmania was again reported negative. A new bone marrow aspirate was sent at the Parasitology Laboratory, Istituto Superiore Sanità, Rome and resulted positive for Leishmania (culture and microscopy). The patient was treated with liposomial amphotericin B 3 mg/Kg/die for 5 days, th plus a further dose on day 10 [1, 2]. The patient was well on discharge and on follow-up, one month later. ■ DISCUSSION The Authors described two patients with visceral leishmaniasis whose clinical features are quite typical but still allows evaluable considerations. Both patients lived in endemic regions for leishmaniasis in Italy [3, 4]. The diagnosis of leishmaniasis had to be considered by the primary health care physicians also because bone marrow hystology was not diagnostic for malignancy. Further more one patient underwent splenectomy, liver and lymphonode biopsy. Spleen biopsy is reported diagnostic of VL in over 95% of cases, liver biopsy and bone marrow sensitivity is reported to be about 70% [1]. Diagnosis of Leishmaniasis relays upon demon- Acknowledgments We thank Dr. Luigi Gradoni, Laboratorio di Parassitologia, Istituto Superiore di Sanità, Rome, Italy for his support. Key words: visceral leishmaniasis, diagnosis, immunocompetent patients. 177 2002 SUMMARY Two cases of visceral leishmaniasis (VL) in immunocompetent patients are described. Both patients lived in endemic areas for leishmaniasis in the south of Italy, and tested positive for anti-Leishmania antibodies. A definitive diagnosis of VL was delayed by false negative microscopic examinations. Both patients were treated successfully with liposomal amphotericin B. Our results show that the search for anti-Leishmania antibodies using the Immuno Fluorescent Assay (IFA) is a valid diagnostic approach. In the two cases examined, it ensured correct diagnosis and therapy. Although microscopy is reported to be highly sensitive and specific in the diagnosis of VL, it may yield false negative results when used in laboratories without high level of expertise. RIASSUNTO Sono descritti due casi di Leishmaniosi viscerale in soggetti immunocompetenti. Entrambi i pazienti residenti in aree endemiche per Leishmaniosi in regioni meridionali d’Italia avevano presentato positività per la ricerca degli anticorpi anti-leishmania. La diagnosi definitiva è stata ritardata dal risultato falso-negativo dell’osservazione microscopica. Entrambi i pazienti sono stati trattati con successo con amfotericina B liposomiale. Conclusioni: la ricerca degli anticorpi anti-leishmania nel siero con il metodo dell’Immuno Fluorescenza (IFA) rappresenta un test diagnostico valido ed utile. Nei due casi descritti ha permesso una corretta diagnosi e terapia. L’esame microscopico pur essendo il metodo diagnostico più sensibile e specifico per la diagnosi di Leishmaniosi viscerale, può condurre a risultati falsi negativi soprattutto quando l’osservazione è effettuata presso laboratori che non hanno adeguata esperienza. ■ REFERENCES Visceral Leishmaniasis in HIV-1-infected individuals: a common opportunistic infection in Spain? AIDS 6, 14991503, 1992. 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