Varied spectrum of clinical presentation and mortality in a prospective registry of visceral leishmaniasis in a low endemicity area of Northern Italy

BMC Infectious Diseases

Andrea De Maria⁴  Giuseppe Ferrea⁵  Claudio Viscoli³  Giovanni Cassola²  Gabriella Pagano³  Maria Grazia Marazzi⁴  Raffaella Giacchino⁴  Marco Anselmo¹  Giovanni Riccio⁸  Manuela Izzo⁸  Valerio Del Bono³  Elisabetta Bondi⁴  Nicoletta Bobbio²  Federica Toscanini¹  Chiara Dentone⁵  Andrea Dusi⁶  Ambra Pasa⁷  Giovanni Cenderello² 

[1]SC Malattie Infettive Ospedale San Paolo ASL2, Savona, Italy

[2]S.C. Malattie Infettive Ente Ospedaliero Ospedali Galliera, Genova, Italy

[3]Clinica Malattie Infettive, IRCCS AOU San Martino-IST Genova, Genova, Italy

[4]Istituto G. Gaslini, Genova, Italy

[5]SC. Malattie Infettive, ASL1 Imperiese-Ospedale Sanremo, Sanremo (IM), Italy

[6]SSD Microbiologia ASL1 Imperiese-Ospedale Sanremo, Sanremo (IM), Italy

[7]S.C. Oncologia Ente Ospedaliero Ospedali Galliera, Genova, Italy

[8]SC Malattie infettive Ospedale Santa Maria della Misericordia Albenga ASL-2, Albenga (SV), Italy

关键词: HIV;    Immunocompromised host;    Visceral leishmaniasis;   

Others  :  1148069
DOI  :  10.1186/1471-2334-13-248

 received in 2012-12-05, accepted in 2013-05-22,  发布年份 2013

【 摘 要 】

Background

Visceral Leishmaniasis (VL) is endemic in 88 countries, in areas of relatively low incidence with a relevant proportion of immune suppressed patients clinical presentation, diagnosis and management may present difficulties and pitfalls.

Methods

Demographic data, clinical, laboratory features and therapeutic findings were recorded in patients identified by a regional VL disease registry from January 2007 to December 2010.

Results

A total of 55 patients (36 adults mean age 48.7 years, 19 children median age 37.5 months) were observed presenting with 65 episodes. All childen were immunocompetent, whereas adults affected by VL included both immunocompetent (n°17) and immunesuppressed (n°19) patients. The clinical presentation was homogeneous in children with predominance of fever and hepato-splenomegaly. A wider spectrum of clinical presentations was observed in immunocompromised adults. Bone marrow detection of intracellular parasites (Giemsa staining) and serology (IFAT) were the most frequently used diagnostic tools. In addition, detection of urinary antigen was used in adult patients with good specificity (90%). Liposomal amphotericin B was the most frequently prescribed first line drug (98.2% of cases) with 100% clinical cure. VL relapses (n°10) represented a crucial finding: they occurred only in adult patients, mainly in immunocompromised patients (40% of HIV, 22% of non-HIV immunocompromised patients, 5,9% of immunocompetent patients). Furthermore, three deaths with VL were reported, all occurring in relapsing immunocompromised patients accounting for a still high overall mortality in this group (15.8%).

Conclusions

The wide spectrum of clinical presentation in immunesuppresed patients and high recurrence rates still represent a clinical challenge accounting for high mortality. Early clinical identification and satisfactory treatment performance with liposomal amphotericin B are confirmed in areas with low-level endemicity and good clinical standards. VL needs continuing attention in endemic areas where increasing numbers of immunocompromised patients at risk are dwelling.

【 授权许可】

   
2013 Cenderello et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]WHO Report on Global Surveillance of Epidemic-prone Infectious Diseases: Chapter ten Leishmaniasis and Leishmania HIV/coinfection: Background Information. WHO; 2009. Available from: http://www.who.int/csr/resources/publications/surveillance/Leishmaniasis.pdf webcite last accessed May 03rd 2012
• [2]Ready PD: Leishmaniasis emergence and climate change. In Climate change: the impact on the epidemiology and control of animal diseases Edited by de la Roque S. 2008, 27:399-412. Rev Sci Tech Off Int Epiz
• [3]Kuillick-Kendrick R: Phlebotomine vectors of the leishmaniases: a review. Med Vet Entomol 1990, 4:1-24.
• [4]Peters N, Sacks D: Immune privilege in site of chronic infection: leishmania and regulatory T cells. Immunol Rev 2006, 213:159-179.
• [5]Hovius E, Pinelli E, Nijsse R, Poot J, van der Giessen J: Introduction of leishmania species in the Netherland from dogs who are returning from military missions and vacations in countries where leishmaniasis is endemic. Tijdschr Diergeneeskd 2011, 136:344-348.
• [6]Maroli M, Rossi L, Baldelli R, Capelli G, Ferroglio E, Genchi C, Gramiccia M, Mortarino M, Pietrobelli M, Gradoni L: The northward spread of leishmaniasis in Italy: evidence from retrospective and ongoing study studies on the canine reservoir and phlebotomine vectors. Trop Med Int Health 2008, 13:256-264.
• [7]Biglino A, Bolla C, Concialdi E, Trisciuoglio A, Romano A, Ferroglio E: Asymptomatic Leishmania infantum infection in Area of Northwestern Italy (Piedmont Region) Where such infections are traditionally nonendemic. J Clin Microbiol 2010, 48:131-136.
• [8]Bogdan C, Schönian G, Bañuls AL, Hide M, Pratlong F, Lorenz E, Röllinghoff M, Mertens R: Visceral leishmaniasis in a child who had never entered a known endemic area: case report and review of the literarature. Clin Inf Dis 2001, 32:302-306.
• [9]Harms G, Schonian G, Feldmeier H: Leishmaniasis in Germany. Emerging Infect Dis 2003, 9:872-875.
• [10]Kumar B, Verma P: Role of fine-needle aspiration cytology in the prompt diagnosis of recurrence of visceral leishmaniasis presented as isolated cervical leishmanial lymphadenopathy. Diagn Cytopathol 2013 Feb, 41(2):150-2.
• [11]Pomares-Estran C, Cenderello G, Ittel A, Karsenti JM, Cardot-Lçeccia N, Vassallo M, Hasseine L, Delaunay P, Rosenthal E, Marty P: Isolated lymphoadenopathy in Leishmania infantum infection:three case reports. Ann Trop Med Parasitol 2009, 103:555-559.
• [12]Bourgeois N, Bastien P, Reynes J, Markinson A, Rouanet I: Active Chronic leishmaniasis in HIV-1 infected patients demonstrated by biological and clinical long term follow up of 10 patients. HIV Med 2010, 11:670-673.
• [13]Cascio A, Iaria M, Iaria C: Leishmaniasis and biologic therapies for rheumatologic diseases. Semin Arthritis Rheum 2010, 40:e3-e5.
• [14]WHO/PAHO: Visceral Leishmaniasis. WHO/PAHO Epidemiol Bull 2002, 23:14.
• [15]Oliva G, Scalone A, Foglia Manzillo V, Gramiccia M, Pagano A, Di Muccio T, Gradoni L: Incidence and time course of Leishmania infantum infections examined by parasitological, serologic, and nested-PCR techniques in a cohort of naive dogs exposed to three consecutive transmission seasons. J Clin Microbiol 2006, 44:1318-1322.
• [16]Bergasa MV: Approach to the patient with liver disease (2007). In Cecil textbook of Medicine. 23rd edition. Edited by Goldman L, Ausiello D. Philadelphia: Saunders Elsevier; 2007:1089-1090.
• [17]World Health Organisation: Nutritional anaemias report of a WHO Scientific Group. World Health Organ Tech Rep Ser 1968, 405:5-37.
• [18]Hsieh MM, Everhart JE, Byrd Holt D, Tisdale JF, Rodgers GP: Prevalence of neutropenia in the US Population: Age Sex, Smoking status, and ethnic differences. Ann Inter Med 2007, 146:486-492.
• [19]Buckley MF, James JW, Brown DE, Whyte GS, Dean MG, Chesterman CN, Donald JA: A novel approach to the assessment of variations in the human platelet count. Thromb Haemost 2000, 83:480-484.
• [20]Lachaud L, Bourgeois N, Plourde M, Leprophon P, Bastien P, Ouellette M: Parasite susceptibility to amphotericin B in failures of treatment for visceral leishmaniasis in patients coinfected with HIV type1 and Leishmania infantum. Clin Infect Dis 2009, 48:e16-e22.
• [21]Buffet PA, Rosenthal É, Gangneux JP, Lightburne E, Couppié P, Morizot G, Lachaud L, Marty P, Dedet JP: Therapy of Leishmaniasis in France: consensus on proposed guidelines. Presse Med 2011, 40:173-184.
• [22]Bern C, Adler-Moore J, Berenguer J, Boelaert M, den Boer M, Davidson RN, Figueras C, Gradoni L, Kafetzis DA, Ritmeijer K, Rosenthal E, Royce C, Russo R, Sundar S, Alvar J: Liposomal Amphotericin B for the Treatment of Visceral Leishmaniasis. Clin Infect Dis 2006, 43:917-924.
• [23]Sundar S, Jha TK, Thakur CP, Engel J, Sindermann H, Fischer C, Junge K, Bryceson A, Berman J: Oral Miltefosine for Indian Visceral Leishmaniasis. N Engl J Med 2002, 347:1739-1746.
• [24]Dujardin JC, Campino L, Cañavate C, Dedet JP, Gradoni L, Soteriadou K, Mazeris A, Ozbel Y, Boelaert M: Spread of vector-borne diseases and neglect of Leishmaniasis. Europe Emerg Infect Dis 2008, 14:1013-1018.
• [25]Chappuis F, Sundar S, Hailu A, Ghalib H, Rijal S, Peeling RW, Alvar J, Boelaert M: Visceral leishmaniasis: what are the needs for diagnosis, treatment and control? Nat Rev Microbio 2007, 5:873-882.
• [26]Cascio A, Colomba C, Antinori S, Orobello M, Paterson D, Titone L: Pediatric visceral leishmaniasis in Western Sicily, Italy: a retrospective analysis of 111 cases. Eur J Clin Microbiol Infect Dis 2002, 21:277-282.
• [27]Minodier P, Piarroux R, Garnier JM, Unal D, Perrimond H, Dumon H: Pediatric visceral leishmaniasis in southern France. Pediatr Infect Dis J 1998, 17:701-704.
• [28]Petrela R, Kuneshka L, Foto E, Zavalani F, Gradoni L: Pediatric Visceral Leishmaniasis in Albania: A retrospective analysis of 1210 Consecutive Hospitalized Patients (1995–2009). PLoS Negl Trop Dis 2010, 4:e814.
• [29]Riera C, Fisa R, Lopez P, Ribera E, Carrió J, Falcó V, Molina I, Gállego M, Portús M: Evaluation of a latex agglutination test (Katex) for detection of Leishmania antigen in urine of patients with HIV -Leishmania coinfection: value in diagnosis and post treatment follow up. Eur J Clin Microbiol Infect Dis 2004, 23:899-904.
• [30]Vilaplana C, Blanco S, Domínguez J, Giménez M, Ausina V, TUral C, Muñoz C: Non invasive method for diagnosis of visceral leishmaniasis by a latex agglutination test for detection of antigens in urine samples. J Clin Microbiol 2004, 42:1853-1854.
• [31]Bern C, Jha SN, Joshi AB, Thakur GD, Bista MB: Use of the recombinant K39dipstick test and the direct agglutination test in a setting endemic for visceral leishmaniasis in Nepal. Am J Trop Med Hyg 2000, 63:153-157.
• [32]Cota GF, De Sousa MR, Rabello A: Predictors of visceral leishmaniasis relapse in HIV-Infected patients: a Systematic review. PLoS Negl Trop Dis 2011, 5:e1153.
• [33]Pasquau F, Ena J, Sanchez R, Cuadrado JM, Amador C, Flores J, Benito C, Redondo C, Lacruz J, Abril V, Onofre J: Leishmaniasis as an opportunistic infection in HIV-infected patients: determinants of relapse and mortality in a collaborative study of 228 episodes in a Mediterreanean region. Eur J Clin Microbiol Infect Dis 2005, 24:411-418.
• [34]Pintado V, Martín-Rabadán P, Rivera ML, Moreno S, Bouza E: Visceral leishmaniasis in human immunodeficiency virus (HIV)-infected and non-HIV-infected patients. A comparative study. Medicine (Baltimore) 2001, 80:54-73.
• [35]Lopez VR, Casado JL, Pintado V: Decline of visceral leishmaniasis epidemic in HIV infected patients after the introduction of highly antiretroviral therapy. Clin Microbiol Infect 2011, 7:394-395.
• [36]Del Giudice P, Mary-Krause M, Pradier C, Grabar S, Dellamonica P, Marty P, Gastaut JA, Costagliola D, Rosenthal E: Impact of highly active antiretroviral therapy on the incidence of Visceral leishmaniasis in a French cohort of patients infected with human immunodeficiency virus. J Infect Dis 2002, 186:1366-1370.
• [37]Bernier R, Turco SJ, Olivier M, Tremblay M: Activation of human immunodeficiency virus type 1 in monocytoid cells by the protozoan parasite Leishmania donovani. J Virol 1995, 69:7282-7285.
• [38]Cacopardo B, Nigro L, Preiser W, Fama A, Satariano MI, Braner J, Celesia BM, Weber B, Russo R, Doerr HW: Prolonged Th2 cell activation and increased viral replication in HIV-Leishmania co-infected patients despite treatment. Trans R Soc Trop Med Hyg 1996, 90:434-435.
• [39]Barão SC, de Fonseca Camargo-Neves VL, Resende MR, Da Silva LJ: Human asymptomatic infection in visceral leishmaniasis: a seroprevalence study in an urban area of low endemicity. Preliminary results. Am J Trop Med Hyg 2007, 77:1051-1053.