Scandinavian Journal of Infectious Diseases

ISSN: 0036-5548 (Print) 1651-1980 (Online) Journal homepage: http://www.tandfonline.com/loi/infd19

Leishmaniasis Diagnosed from Bronchoalveolar Lavage Liisa Jokipii, Kaija Salmela, Heikki Saha, Hannu Kyrönseppä, BjÖRn Eklund, David Evans, Eeva Von Willebrand & Anssi M. M. Jokipii To cite this article: Liisa Jokipii, Kaija Salmela, Heikki Saha, Hannu Kyrönseppä, BjÖRn Eklund, David Evans, Eeva Von Willebrand & Anssi M. M. Jokipii (1992) Leishmaniasis Diagnosed from Bronchoalveolar Lavage, Scandinavian Journal of Infectious Diseases, 24:5, 677-681, DOI: 10.3109/00365549209054657 To link to this article: http://dx.doi.org/10.3109/00365549209054657

Published online: 08 Jul 2009.

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Date: 02 April 2016, At: 14:39

Scand J Infect Dis 24: 677481, 1992

CASE REPORT

Leishmaniasis Diagnosed from Bronchoalveolar Lavage

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LIISA JOKIPII', KAIJA SALMELA', HEIKKI SAHA', HANNU KYRONSEPPA3, BJORN EKLUND', DAVID EVANS', EEVA VON WILLEBRAND' and ANSSI M. M. JOKIPII' From the 'Department of Serology and Bacteriology, University of Helsinki, 'Division of Trutisplantation. 4th Department of Surgery, University of Helsinki, .'Aurora Hospital. Helsinki, Finland, 'London School of Hygiene and Tropical Medicine, London, U.K., 'Trtrrr.~plunti~tion Laboratory. University of Helsinki, Helsinki, and 'Department of Medical Microbiology, University of Turku, Turku, Finland

A 51-year-old renal transplant patient, whose spleen had been removed 11 years ago, was admitted to hospital for elective surgery, which was cancelled as she developed spiking fever and nonproductive cough and her general condition deteriorated. After 2 weeks, leishmaniasis was unexpectedly diagnosed from a bronchoalveolar lavage specimen, which had been subjected to parasitological examination under the suspicion of pneumocystosis. lsoenzyme typing identified the parasite as Leishmania infantum. The patient had visited Malaga, Spain, twice a year. the last trip taking place 1 month before admission. Specific treatment was followed by rapid recovery without relapse during 1.5 years. Splenectomy and immunosuppressive medication obscured the clinical suspicion of leishmaniasis. The case is a reminder of the interstitial pneumonitis in leishmaniasis and emphasizes the value of broad-spectrum methods detecting a variety of parasites. L . Jokipii, M D , Department of Serology and Bacteriology, University of Helsinki, Haartma-

ninkatu 3 B , SF-00290 Helsinki, Finland

INTRODUCTION Sporadic visceral leishmaniasis outside endemic areas is being reported with increasing frequency and from an increasing number of countries in Europe. Previously healthy subjects have been involved in Sweden (1,2), France (3,4), England (5,6), Germany (7-ll), Finland (12), Belgium (13). Denmark (14,15), Switzerland (16), Italy (17), and Norway (18) including several fatal cases. More recently and more conspicuously, cases have emerged in compromised hosts, as exemplified by renal transplant recipients with immunosuppressive therapy either in countries with endemic leishmaniasis (19-21) or elsewhere (22,23). Reduced infection resistance is not needed to contract leishmaniasis, but the disease in compromised hosts is gaining importance, because their numbers and ability to travel normally are increasing rapidly, and the combination of an unlikely geographic location and an atypical host effectively masks the correct diagnosis. Furthermore, this potentially fatal infection can be eradicated if diagnosed. We describe a renal transplant patient with unsuspected visceral leishmaniasis diagnosed from a bronchoalveolar lavage specimen. CASE REPORT A 51-year-old woman was admitted to hospital for elective surgery of an intrapelvic lymphocele, a complication of a cadaver kidney transplant operation 4 months earlier. I n her past history she had severe pancreatitis in 1968, complicated by renal cortical necrosis leading to impaired renal function. 10 years later she underwent pancreatic resection and splenectomy. Soon

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Fig. I. Intracellular leishmania amastigotes in cytocentrifuged BAL fluid (Giemsa, ~ 2 0 0 0 ) . after this operation, end stage renal disease developed. After 7 months on haemodialysis, she received a kidney transplant donated by her sister. The patient was doing well until the graft function failed from chronic rejection after 11 years. After a short period of continuous ambulatory peritoneal dialysis treatment she received a second kidney transplant of cadaveric origin. Three weeks after the uneventful transplant operation she was discharged from hospital with stable kidney function (serum creatinine 182 pmol/l). No acute allograft rejection episodes were encountered. The basic immunosuppressive medication was azathioprine, methylprednisolone and cyclosporin. A combination of trimethoprim-sulphamethoxazole as prophylaxis against pneumocystis for 3 months was initiated. The patient had been symptomless except for the inconvenience caused by a postoperative intrapelvic lymphocele verified in ultrasound examination. The increasing volume of the lymphocele caused lymphoedema of the ipsilateral leg and dysuria. An elective intraperitoneal fenestration of the lymphocele was planned, but as the patient developed pyrexia, surgery was cancelled. Peaks of fever reached 40°C in the mornings, and she had a nonproductive cough. Her general condition deteriorated slowly, though she remained ambulant. The leukocyte count was 2.6 X 109/1,haernoglobin 73 gll, haematocrit 22. thrombocyte count 160 x 109/1, C-reactive protein 150 mg/l and serum alanine transferase 122 U/I. There was a marked dysproteinaemia with serum albumin 23.9 g/1 and gamma globulin 27.0 g/1 (which was mainly due to the increased IgG fraction with only a slight increase in IgM). No lymphadenopathy was noted, the chest X-ray was normal, and the kidney transplant function remained normal. Blood cultures were negative for bacteria. After 2 weeks of spiking fever and cough a bronchoalveolar lavage (BAL) was carried out. The harvested cells were transferred on microscope slides by cytocentrifugation. Some of them were sent to the parasitological laboratory for a possible detection of pneumocystis. Unexpectedly, in a giemsastained slide a few cells with up to 15 inclusion bodies resembling leishmania amastigotes were detected (Fig. I ) . A bone marrow aspirate verified the finding, the leishmania strain was also cultivated on NNN-agar, and later on proved by isoenzyme studies to be Leishmania infantum. Leishmania amastigotes were also detectable in blood monocytes obtained by fine needle aspiration from the transplanted kidney. In addition, in the BAL cells there were inclusions caused by cytomegalovirus, which were subsequently eradicated by specific antiviral treatment. Anti-leishmania antibodies were positive to titres of 160 (indirect immunofluorescence, Statens Bakteriologiska Laboratorium, Stockholm, Sweden). The patient received as treatment against visceral leishmaniasis intramuscular sodium stibogluconate (Pentostam@), 10 mg/kg/day for 20 days. The fever subsided within 5 days and her subjective recovery was rapid. Bone marrow aspirate performed after therapy was negative for leishmania. Other infection parameters became and have remained normal, the titre of anti-leishmania antibodies decreased to 10 in 3 months, and no relapse has occurred during 1.5 years’ follow-up. Since the onset of fever, anaemia and leukopenia, azathioprine was withdrawn, but the other immunosuppressive drugs were continued, and the kidney transplant function has remained unaffected. Three months after the transplantation and 1 month prior to admission the patient had visited her sister in Malaga, Spain, as she had done twice a year also previously. She had stayed in an urban area, except for a picnic by a small pond in the countryside.

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DISCUSSION Thc case focuses attention to a number of points concerning the diagnosis of fever of unknown origin. These are particularly relevant with a disease like visceral leishmaniasis, which is potentially fatal but has a good prognosis if correctly diagnosed and treated. Kala-azar in Europe has been regarded as a rare tropical disease, but is relatively easily suspected in connection with a patient’s exotic travelling history. Unfortunately this clue is no longer helpful: the possibility of visceral leishmaniasis can seldom be excluded by a lacking travelling history, as trips to Mediterranean areas endemic for Leishmania infanturn have become so common. The present patient could have been infected during her visit to Malaga 1 month before the onset of fever, or the same place earlier, or possibly via any of several blood transfusions. Even the kidney transplant cannot be excluded as the source of infection. The vehicle in 3 earlier Swedish o r Finnish cases in children has been blood (2,12). The incubation period cannot be estimated with any certainty, but the identification of the parasite as Leishmania infantum points to but does not prove Mediterranean origin. Knowledge of the hallmark clinical features of visceral leishmaniasis was not sufficient to arouse the pertinent suspicion in this case. Hepatomegaly or lymphadenopathy were not observed, and the patient’s spleen had been removed. Anaemia, leukopenia and thrombocytopenia were found but not unexpected in the immunosuppressed subject, and, on the other hand, they are not necessarily found in visceral leishmaniasis where the spleen has been removed. Of 7 published cases of visceral leishmaniasis in renal transplant recipients 5 have been fatal (19-23). Five cases occurred in an endemic area, Spain (19-21) and the remaining 2 patients had been infected during trips to the Mediterranean (22,23). It seems that Leishmania infantum was responsible for all cases, although previous authors did not carry out parasitological identification - apparently because isoenzyme typing was not available. A s in our case, pancytopenia was present but attributed to the immunosuppressive medication, thus failing to facilitate the diagnosis. Splenomegaly was absent in half the cases, even though the spleen had not been removed, as in our case. The present patient had typical dysproteinaemia. but in the earlier reports the relevant information is lacking, so the regularity of this laboratory parameter cannot be evaluated. The diagnosis of leishmaniasis was fortuitous in many cases as in ours. Diagnostic difficulties have been the rule and obviously contributed t o the fatal outcome. Interstitial pneumonitis is a characteristic of visceral leishmaniasis, and has been detected in most cases studied at autopsy (24-27). These cases were, however, visceral leishmaniasis of Asian or South American origin, but there is no reason to assume that Leishmania infanturn should behave differently. A case of pleurisy has been diagnosed in France (28). Cough is a common and early symptom of visceral leishmaniasis. However, there is no information on the efficacy of antemortem efforts to diagnose lung involvement by leishmania. Accordingly, it is not known what proportion of cases of visceral leishmaniasis could be diagnosed from B A L specimens. Our immunocompromised patient’s nonproductive cough suggested pneumocystosis so a parasitological investigation was performed, which unexpectedly revealed leishmania. The finding prompts a word of caution against highly specific laboratory methods, which are being adopted increasingly. Antigen detection methods, including the use of monoclonal antibodies, are advocated for the diagnosis of pneumocystis. Should such methods replace broad-spectrum parasitological investigation, the chances of diagnosing leishmania in interstitial pneumonitis would become nil. The laboratory expertise needed, even when the clinical suspicion is there, also would decline progressively, if the relevant specimens became rare. The present case illustrates, why such a development would be unfortunate. It

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suggests, together with the known high frequency of interstitial pneumonitis in visceral leishmaniasis, the need for the opposite, i.e. the investigation of BAL specimens with an eye open for leishmania. The number of immunocompromised individuals able to travel widely is constantly increasing thanks to modern medicine. The probability of reencountering the diagnostic peculiarities, which we have discussed, is likewise increasing.

ACKNOWLEDGEMENTS

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We thank the patient for consent to publish, Mrs Riitta Vesterinen for technical assistance, and the Sigrid JusClius Foundation for a grant to LJ.

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Leishmaniasis diagnosed from bronchoalveolar lavage.

A 51-year-old renal transplant patient, whose spleen had been removed 11 years ago, was admitted to hospital for elective surgery, which was cancelled...
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