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Visceral leishmaniasis is a vector-borne disease essentially associated with Leishmania infantum infection in the Mediterranean basin. Although rare in adults, its prevalence has recently increased even among immunocompetent individuals. The aim of our study is to reveal the epidemiological features of visceral leishmaniasis in adults and the importance of biological diagnostic in the identification of this disease. Our study spanned six years from January 2009 to January 2014 and data were collected from twelve patients hospitalized at University Hospital Hassan II, Fez. Alteration of general state and splenomegaly dominated the clinical picture. Biologically, anemia was almost constant. Diagnosis was confirmed by parasite identification at the level of bone marrow. The response to treatment was favorable for all our patients. Thus, visceral leishmaniasis recrudescence in adults and its nonspecific clinical picture must lead the clinicians to suspect it when fever accompanying splenomegaly occurs, thus enabling early diagnosis and therapeutic management. [ABSTRACT FROM AUTHOR]

Résumé: La leishmaniose viscérale (LV) associée au syndrome d’hémophagocytose lympho-histiocytaire (HLH) chez l’enfant est une entité clinico-pathologique rare, de diagnostic difficile, mortelle en l’absence de traitement. Chez l’enfant, il faut l’évoquer devant un tableau clinique de fièvre prolongée avec splénomégalie. Nous rapportons deux observations d’HLH secondaire à une LV. Dans la première observation, il s’agissait d’un jeune nourrisson de 3 mois et demi hospitalisé pour une tricytopénie fébrile. Le diagnostic d’HLH avait été posé devant un tableau clinico-biologique complet incluant une hémophagocytose sur le myélogramme. La recherche d’une maladie génétique, métabolique ou d’une infection sous-jacente avait été négative. Une cause primitive d’HLH avait été d’emblée évoquée et un traitement immunosuppresseur (corticoïdes et ciclosporine) avait été instauré. Un myélogramme de contrôle à un mois d’évolution ayant retrouvé des leishmanies, l’évolution avait été rapidement favorable sous traitement par amphotéricine B liposomale. Dans la deuxième observation, il s’agissait d’un enfant de 10ans avec de multiples antécédents infectieux, hospitalisé pour une tricytopénie fébrile avec syndrome tumoral. Le diagnostic de LV avait été posé sur le myélogramme et un traitement par amphotéricine B liposomale avait été mis en route. Au 3e jour de traitement, une corticothérapie avait été instaurée devant l’apparition d’une HLH. Un déficit immunitaire héréditaire sous-jacent par défaut de l’axe interleukine-12 (IL-12) et interféron-γ (IFN- γ) avait été diagnostiqué devant l’évolution atypique de la LV sous traitement. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Studying the epidemiological variations of visceral leishmaniasis in Tunisia and proving the importance of parasitological investigations to raise the diagnosis. Patients and methods: Six patients hospitalised during the period between January 1998 and January 2009 at Fattouma Bourguiba Teaching Hospital in Monastir, five men and an only one woman, aged from 26 to 70 years old, originating from the central and eastern regions of the country. Epidemiological, clinical, biological and therapeutic data were obtained from the patient''s medical files. Results: The major clinical symptoms were fever, weakness and spleen enlargement. Biological data revealed the presence of anaemia in every case and leucopoenia associated or not associated with thrombopenia in four cases. The diagnosis of visceral leishmaniasis was confirmed by the identification of the parasite in the blood or in the bone marrow. All patients were treated with two courses of antimoniate of meglumine separated by a 6-week interval. The outcome was positive and the patients were cured. Conclusion: Visceral leishmaniasis is increasing among adults in Tunisia. Moreover, it is spreading outside its epidemiological area in the north to reach the central and southern regions. It should be raised when fever and spleen enlargement occur. Biological data are hardly specific. Diagnosis is based on finding the parasite in human fluids, mainly by molecular techniques. The rapid establishment of a specific treatment is vital. [Copyright &y& Elsevier]

Abstract: Objective: The authors retrospectively studied the epidemiological, clinical, diagnostic and therapeutic aspects of 71 cases of visceral leishmaniasis from 1998 to 2009. Population and methods: The diagnosis was made by finding Leishmania amastigotes in bone marrows smears and/or by serology. Results: Most cases occur in winter (35.2%) and in spring (36.6%). The source areas are endemic ones located in the north of Algeria (74.6%) and more rarely arid or semi-arid climate areas (8.4%). 88.7% of patients are children. The sex ratio is 1.53. The clinical characteristics are: fever (77.4%), paleness (43.6%); splenomegaly (83%), hepatomegaly (57.7%). The biological anomalies are: anemia (56.3%), thrombocytopenia (33.8%), and leucopenia (28.1%). N-methylglucamine (Glucantime®) was most often prescribed (70.4%). Four deaths (5.6%) were recorded. Conclusion: Visceral leishmaniasis remains a pediatric affection but does not spare adults. [Copyright &y& Elsevier]

Abstract: During the last decade, visceral leishmaniasis has been reconsidered in its epidemiology and strategies for diagnosis, treatment and prevention. This vectorial disease, responsible for more than 50,000 deaths each year across India, East Africa, South America, the Mediterranean area, Central Asia and China, is currently spreading over new territories. This formerly rural disease has even reached cities in South America. This spreading is caused by environmental changes due to global warming or human activity, and by the movement of workers and refugees. As a consequence, the burden of HIV/Leishmania coinfection is increasing in many developing countries even though effective antiretroviral therapy has led to a marked decrease in its incidence in Europe. The disease is now handled differently than it was 10 years ago: PCR has become the most accurate tool for diagnosis and follow-up in developed countries, and field diagnostic tools have been developed (antigenuria, rK39 dipstick). While resistance to antimoniate has appeared in India and Europe, new therapies have been evaluated such as miltefosine, the first oral therapy, or short treatment with liposomal amphotericin B. In France, liposomal amphotericin B has supplanted antimoniate meglumine because of better tolerance and shorter hospitalization duration. Protecting dogs through immunization or collars impregnated with deltamethrin proved effective to prevent zoonotic leishmaniasis due to Leishmania infantum. [Copyright &y& Elsevier]

Abstract: Leishmaniases in Morocco are endemic diseases. Three forms of leishmaniasis are reported, visceral leishmaniasis, cutaneous leishmaniasis caused by Leishmania tropica and cutaneous lesions due to Leishmania major. Leishmania infantum, a common parasite inducing visceral leishmaniasis, was observed thereafter in cutaneous lesions. The first case of cutaneous leishmaniasis due to L. tropica was isolated since 1987. But, this parasite was shown to be more polymorphic with almost 8 zymodemes. However, these zymodemes are not all transmitted by Phlebotomus sergenti and not all isolated from human reservoir. Regarding the clinical aspect, cutaneous leishmaniasis with L. tropica is described as a single lesion starting as a nodule at the site of inoculation. A crust develops centrally which may fall away exposing an ulcer which heals gradually. The second cutaneous form is that caused by Leishmania major. It was known in villages located in the southern slopes of the Atlas Mountains. Clinically, the lesion is often severely inflamed and ulcerated and heals in 4–6 months. The epidemiologic cycle of this rural form, include Phlebotomus papatasi as the proven vector and a commensally rodent, Meriones shawi grandis as the reservoir. However, visceral leishmaniasis in Morocco has been known since 1921. It is especially located in the North. The responsible parasite is L. infantum MON 1. Two species of the sand fly are involved in the transmission of this form, P. ariasi and P. perniciosus. In infected man, the clinical signs are non-tender splenomegaly, with or without hepatomegaly, wasting and pallor of mucous membranes. Even though L. infantum MON1 is responsible of the disease, some canine cases were reported to be caused by Leishmania tropica. [Copyright &y& Elsevier]

Summary: The association of hemophagocytic syndrome (HS) and visceral leishmaniasis is a frequent disorder during infancy in endemic areas such as Tunisia. The range of severity of HS secondary to visceral leishmaniasis includes both pure biological forms that resolve with antimicrobial therapy and life-threatening emergencies that require specific treatment. We describe 2 cases of severe HS secondary to visceral leishmaniasis. The diagnosis of HS was based on the HLH-2004 diagnostic criteria. Therapy involved pentavalent antimonial (Glucantime®) in both cases. The combination of corticosteroids with immunoglobulins, used in the 1st case, but introduced late, led to an unfavorable course and death. In the 2nd case, the specific treatment of HS was based on immunochemotherapy including etoposide and corticosteroids. Progression was favorable with a follow-up of 24 months. Etoposide containing therapeutic regimens can be proposed in severe forms of HS associated with visceral leishmaniasis. [ABSTRACT FROM AUTHOR]

Abstract: Cutaneous and visceral leishmaniasis (VL, CL) represent the most frequent vector-borne diseases in Tunisia. Their biological confirmation is necessary before the administration of restricting, expensive and toxic specific treatments. Retrospective evaluation of the contribution of Leishmania cultures on NNN medium in leishmaniasis diagnosis have been done using the data of 375 cultures concerning 214 CL cases and 125 VL cases consecutively recruited in Pasteur Institute of Tunisia between 1995 and 2007. The global sensitivity of the culture in the course of CL was of 68.2%. It was significantly higher during zoonotic CL (78.8%) compared to that during sporadic CL (54.9%); p <0.001. This difference is explained by the easier thrust in NNN medium of Leishmania (L.) major, the agent of zoonotic CL than that of L. infantum, particularly its zymodeme MON-24, agent of sporadic CL. In the course of VL, and in spite of the better sensitivity of bone marrow aspirates (BMA) culture (70.8%), the blood buffy-coat, which permit to avoid the trauma induced by BM aspiration gave promising results (58.2%), the difference being not significant. Besides, in the course of both CL and VL, the direct examination of smears is revealed more sensitive, respectively 89.7% and 93.4% (p <0.01 and p <0.01). Although, systematic cultures practise, in parallel with direct examination, is recommended. In fact, in addition of straightening out some diagnosis, 22 cases in our series, the culture provide the isolation and the isoenzymatic identification of the causative species and strains allowing a better comprehend of parasite life cycles and a disposing of important epidemiological data for suitable control measures. As known with all cultures, those of Leishmania are also exposed to the contamination problem, which reached 5.9% in our study. In conformity with previsions, the contamination concerned much more cutaneous samples (8.4%) than blood or BM ones (2.5%; p =0.015). [Copyright &y& Elsevier]

Abstract: The number of visceral leishmaniasis (VL) cases is in continuous growth in Mediterranean countries. In Tunisia, in addition to the traditional infantile form, more and more cases in immunocompetent or immunocompromised adults have been reported. However, co-infection VL–HIV remains rare in Tunisia and diagnosis of all the cases up till now has been done using traditional techniques (serology, direct examination and culture of bone marrow). However, the last years, several studies proved the greatest sensitivity of PCR in VL diagnosis. We carried out a systematic detection of Leishmania in peripheral blood for 25 HIV infected patients (10 were asymptomatic, 6 presented a fever and/or a paleness and/or an asthenia, and 9 had an opportunist infection other than VL). In all cases, the culture on Novy-Nicolle-McNeal (NNN) medium was negative by the end of the month. Serology carried out for 22 patients was negative in IFI in 17 cases, positive at the 1/20 for four others and positive at the 1/40 for one patient (confirmed by Western Blot technique). A PCR using the primers Lei70L–Lei70R, specific of the gene of Leishmania infantum, allowed the display of the specific band of 345 bp for 17 samples. The higher sensitivity of PCR compared to conventional methods is subject to the difficulty of result interpretation in PCR positive testing among patients not having any other marker of the disease which raises the question of significance for this asymptomatic bearing. [Copyright &y& Elsevier]

Abstract: Infantile visceral leishmaniasis (IVL), or Kala Azar, is a parasitic disease caused by the proliferation of a protozoan parasite Leishmania in the reticulo-histiocyte system. It is characterized by its geographical distribution most frequently in the Mediterranean area, India, East Africa and South America. In Morocco, during these last years, we are witnessing a significant recrudescence mainly in young child. The authors performed a retrospective study of 209 cases of visceral leishmaniasis admitted to the service of pediatrics at the University Hospital of Fez (CHU Hassan II) during a six-year period from January 1998 to December 2004. The average age of our patients is 3.7 years and boys are more affected (sex-ratio=1.45) 90% of the cases come from the suburbs of Fez, primarily from Taounate. The average time of consultation is 2.26 months. The main reasons are abdominal distension (68%), fever (94.5%) and the paleness (50%); rarely a hemorrhagic syndrome (8.5%). The clinical examination shows anaemia in 90% of the cases, fever in 92.6% of the cases and splenomegaly in 97.66% of the cases. The diagnosis is confirmed by the myelogram and the serology of leishmaniasis in 91.3% of the cases. Average diagnosis time is eight days. The identification of the parasite is achieved in collaboration with the Pasteur Institute of Casablanca and Leishmania infantum zymodeme-1 is detected in 100% of the cases. The treatment is based on glucantime at the dose of 80 to 100 mg/kg per day during 21 to 30 days and is efficient in 95.57% of the cases. We deplored six deaths which occurred due to malnutrition and probably in association with a macrophage activation syndrome. Infantile visceral leishmaniasis is the most frequent zoonosis in Morocco. Fez and its suburbs are an area of high endemicity. Its eradication must initially be based on improving socioeconomic conditions as well as fighting against malnutrition, which is a risk factor. [Copyright &y& Elsevier]

Abstract: Aims of the study. – First, to describe liposomal amphotericin B (AmBisome®) use as first line treatment of pediatric visceral leishmaniasis and secondly, to evaluate the incidence of the disease in southern France (Provence – Alpes – Côte d''Azur – Corse). Material and methods. – Retrospective chart review of children referred for visceral leishmaniasis from 1996 to 2003. Results. – Thirty-two children under 15 years of age and suffering from visceral leishmaniasis were treated with liposomal amphotericin B as first line treatment. Clinical and biological features were usual: age &#60;5 years, no immunodeficiency, spleen enlargement and fever, cytopenia. In this population, treatment effectiveness was evaluated to 97% (one relapse). Under treatment, patients quickly improved. Drug regimens varied from 18 to 24 mg/kg (day 1 to 5, and day 10). Four other children were not treated with first-line liposomal amphotericin B during the period. Thus, the incidence of pediatric visceral leishmaniasis was evaluated to be 0.61/100,000 children &#60;15 years/year in the region (2.74 in the Alpes-Maritimes department, French Riviera, and 0.6 in the Bouches-du-Rhône department, Marseilles area). Conclusion. – Liposomal amphotericin B treatment is usual for children referred for visceral leishmaniasis in this region. This treatment may be approved regarding the high level of effectiveness and the low number of adverse events. A two days drug regimen with 20 mg/kg should be evaluated. Moreover, the incidence of the pediatric visceral leishmaniasis in southern France is decreasing, but local variations may be observed. [Copyright &y& Elsevier]

Objective – The epidemiological variations of visceral leishmaniasis (VL) in Tunisia are studied along with the clinical specificity of the disease in adults.Patients and methods – Six cases of parasitologically confirmed adult VL are described.Results – All patients tested negative for HIV. Clinical manifestations were not always evocative. In fact, two patients were apyretic and splenomegaly was absent in three. Biological disorders were more frequently noted, especially increase of erythrocyte sedimentation rate, anemia, and hyper γ globulinemia.Conclusion – The epidemiological profile of VL in Tunisia is slowly becoming identical to the North Mediterranean model characterized by a high proportion of adult cases. This may be due to the multiplication of immunodepressing factors and the decrease of specific immunization following the less frequent human-parasite contact during childhood. [Copyright &y& Elsevier]

Résumé: La leishmaniose viscérale est une protozoose habituellement asymptomatique qui peut évoluer vers une maladie mortelle chez les sujets immunodéprimés, particulièrement ceux infectés par le VIH. Elle est rare chez les patients sous traitement immunosuppresseur et encore plus rare chez ceux traités par anti-TNF-α où seulement quatre cas ont été rapportés. Nous rapportons l’observation d’un patient traité par adalimumab pour une polyarthrite rhumatoïde, chez lequel est apparu un tableau associant une fièvre, une pancytopénie, une splénomégalie et une hyperferritinémie majeure. Nous avons effectué une revue des cas publiés (PubMed 1991–2008) qui associaient, soit une leishmaniose viscérale et un traitement anti-TNF-α, soit une leishmaniose et un syndrome d’activation macrophagique. Le diagnostic de leishmaniose viscérale a été porté par le myélogramme. Le diagnostic de syndrome d’activation macrophagique a été établi, en l’absence de preuve histologique, selon les critères HLH-2004. L’évolution du patient a été favorable. Nous rapportons ici le cinquième cas de leishmaniose viscérale chez un patient traité par anti-TNF-α et le premier, à notre connaissance, à présenter un syndrome d’activation macrophagique associé. [Copyright &y& Elsevier]

Abstract: Objective: The authors had for aim to determine the role of leukoconcentration in the diagnosis of visceral leishmaniosis in immunocompetent children. Materials and methods: A study was made on leukoconcentration in blood samples of 84 immunocompetent children presenting with visceral leishmaniosis, hospitalised in the paediatric units of Sousse and Kairouan (Tunisian center) between April 1996 and March 2005. Results: The study group included 34 girls and 50 boys (sex-ratio=1.47) aged six months to ten years. In this group, 47 patients (56%) presented with positive leukoconcentration. The number of leishmania detected ranged from 1 to 64 per slide; parasitism of PMN leucocytes was noted in nearly half of the cases. Conclusion: Parasitemia is frequent in the Mediterranean Kala-azar; therefore leukoconcentration on peripheral blood can be proposed as a first intention examination for the diagnosis of visceral leishmaniosis in immunocompetent children. [Copyright &y& Elsevier]

Abstract: Visceral leishmaniasis due to Leishmania infuntum is endemic in Tunisia. The incidence in adult patients has increased in recent years; but most of these patients are not HIV positive as in other Mediterranean countries where all the cases are associated with HIV. We present the case of a woman with symptoms suggestive of leishmaniasis but whose bone marrow was sterile and whose serological tests for Leishmania spp. were negative. For this patient, the parasite was only detected in a routine duodenal biopsy. There are few reports of visceral leishmaniasis cases diagnosed by duodenal biopsy and almost all patients were HIV positive in that case. Thus it seems interesting to perform a duodenal biopsy in case of a difficult diagnostic even in the absence of gastrointestinal symptoms and/or HIV infection. [Copyright &y& Elsevier]

Summary: Visceral leishmaniasis is endemic around Mediterranean and is considered by certain authors as an opportunist disease. We report on the case of a 7-year-old girl treated by anti-TNF for an idiopathic juvenile arthritis which has presented a visceral leishmaniasis. Four years later, she presented a pseudotumoral-like recurrence located in a nasal mucous membrane. Leishmania infantum is classically responsible for visceral leishmaniasis but pure mucocutaneous leismaniasis has been described. It is, for our knowledge, the first observation of a recurrence of visceral leishmaniasis in a mucocutaneous location. Atypical leishmaniasis in the endemic zones can appear in immunodepressed patients and must be evoked when in doubt. [Copyright &y& Elsevier]