Leishmaniasis in Turkey

Leishmaniases are widespread in most countries in the Mediterranean basin, including Turkey. Two forms are observed in Turkey; Leishmania infantum is responsible from visceral leishmaniasis (VL), and L. tropica causes cutaneous leishmaniasis (CL). Phlebotomus sergenti, P. papatasi, P. major and P. syriacus are considered to be the probable vectors, and dogs are the main reservoir of L. infantum, while P. sergenti is the main suspected vector of L. tropica.VL is sporadically seen mainly in the Aegean, Mediterranean, and Central Anatolia Regions, but CL is endemic, especially in the Southeastern and Mediterranean Regions. Major touristic sites are free of both infections, and no infection is reported in any tourist. Mean number of annual VL and CL cases reported to Ministry of Health are 40 and 1,204, respectively, in the last four years.These data suggest that both VL and CL represent a public health problem in Turkey, but a decline is observed in the number of cases with both infections in recent years.     

Re-emergence of visceral and cutaneous leishmaniasis in the Greek Island of Crete

Leishmaniases are vector-borne diseases transmitted by phlebotomine sand flies. Three species of Leishmania are found in the Mediterranean basin: Leishmania infantum, the most common species responsible for both visceral (VL) and cutaneous leishmaniasis (CL); Leishmania major, found in North Africa and Middle East causing CL; Leishmania tropica with a limited presence in Europe, causing CL. During the last 25 years, Crete has become an endemic zone for L. infantum with a high number of infected dogs and an increasing number of human cases every year; in the last 4 years, the incidence has reached an average of seven VL patients per year in a population of 600,000. At the same time, CL has re-emerged in Crete due to L. tropica, with an average of three CL cases per year in the last 4 years. Isolates were typed as L. infantum MON-1 and MON-98 and L. tropica MON-300, a zymodeme not reported before. Both VL and CL have spread to the whole of the island during the last 25 years, primarily in semi-urban and urban areas with altitudes of 0-50?m. The prevailing Phlebotomus species were Phlebotomus neglectus (proven vector of L. infantum) and Phlebotomus similis (suspected vector of L. tropica).     

Clinical epidemiologic profile of a cohort of post-kala-azar dermal leishmaniasis patients in Bihar, India

Post-kala-azar dermal leishmaniasis (PKDL) has important public health implications for transmission of visceral leishmaniasis (VL). Clinical and epidemiologic profiles of 102 PKDL patients showed that median age of males and females at the time of diagnosis was significantly different (P = 0.013). A significant association was observed between family history of VL and sex of PKDL patients (χ(2) = 5.72, P < 0.01). Nearly 33% of the patients showed development of PKDL within one year of VL treatment. The observed time (median = 12 months) between appearance of lesions and diagnosis is an important factor in VL transmission. A significant association was observed between type of lesions and duration of appearance after VL treatment (χ(2) = 6.59, P = 0.001). Because PKDL was observed during treatment with all currently used anti-leishmanial drugs, new drug regimens having high cure rates and potential to lower the PKDL incidence need to be investigated.     

Leishmaniasis in Bahia, Brazil: evidence that Leishmania amazonensis produces a wide spectrum of clinical disease

One hundred fourteen Leishmania isolates from patients with different clinical forms of leishmaniasis in the State of Bahia, Brazil, were characterized by indirect radioimmune binding assay using specific monoclonal antibodies (serodeme analysis). Seventy-five of these isolates were also analyzed by enzyme electrophoresis, based on 11 enzyme loci; parasite species were compared, according to their characteristic zymodemes, to those of WHO Leishmania reference strains. All isolates could be classified into one of three species: Leishmania amazonensis (n = 40), L. braziliensis (n = 39) or L. chagasi (n = 35). The most interesting information obtained from this study is the realization that L. amazonensis is capable of producing a wide spectrum of disease in humans. Infection with this parasite was associated with many different clinical presentations, including cutaneous leishmaniasis [CL] (20/49 cases), mucocutaneous leishmaniasis [MCL] (5/13 cases) and, of special note, visceral leishmaniasis [VL] (11/46 cases), as well as four cases of post kalaazar dermal leishmaniasis [PKDL]. In situ tissue parasite characterization, by immunoperoxidase assay and employing anti-L. amazonensis amastigote monoclonal antibodies, confirmed the infection with this species in two cases of CL, one case of DCL, one case of MCL and one case of PKDL. Our results also demonstrate the difficulty of parasite differentiation based on clinical grounds, since at least L. amazonensis infection can be associated with all types of leishmanial diseases, and different Leishmania species may be associated with indistinguishable clinical presentations. Since leishmanial parasites may vary in their biological behavior or in their response to treatment, it is important that their identification be made by reliable methods.     

Post‐kala‐azar dermal leishmaniasis in visceral leishmaniasis‐endemic communities in Bihar,India

We assessed the prevalence of post‐kala‐azar dermal leishmaniasis (PKDL), a late cutaneous manifestation of visceral leishmaniasis (VL), in 16 VL‐endemic communities in Bihar, India. The prevalence of confirmed PKDL cases was 4.4 per 10 000 individuals and 7.8 if probable cases were also considered. The clinical history and treatment of the post‐kala‐azar dermal leishmaniasis cases are discussed.     

Short communication: Post‐kala‐azar dermal leishmaniasis: does it play a role in the transmission of Leishmania donovani in the Sudan?

In 1997 a sudden outbreak of visceral leishmaniasis (VL) occurred in eastern Sudan, coinciding with an increase of post-kala-azar dermal leishmaniasis (PKDL) cases which may in part be because of sylvatic and anthroponotic transmission. Paradoxically, the more VL patients are treated, the higher the frequency of PKDL. If PKDL plays a role in transmission, its treatment would be expected to reduce infection in the area. Treatment of PKDL, however, requires four times the amount of Pentostam used for treating VL, and the drug is both expensive and in short supply.     

Successful treatment of post-kala-azar dermal leishmaniasis (PKDL) in a HIV infected patient with multiple relapsing leishmaniasis from Western Europe

We present a 42-year-old man who was admitted with worsening of his general condition and facial skin lesions. He had previously been diagnosed with HIV infection and visceral leishmaniasis (VL). Diagnostic work-up revealed a new relapse of VL paralleled by the diagnosis of post-kala-azar dermal leishmaniasis (PKDL). The patient was treated with IV liposomal amphotericin B as well as sodium stibogluconate followed by oral hexadecylphosphocholine (miltefosine) over a period of 9 months. PKDL lesions began to disappear after 8 months of treatment. In addition, severe and relapsing VL so far remains in remission. This case demonstrates successful treatment of PKDL and relapsing VL in a Western European patient with HIV infection.     

Epidemiology and clinical manifestations of Leishmania donovani infection in two villages in an endemic area in eastern Sudan

We conducted a longitudinal study in an endemic area for visceral leishmaniasis (VL) in eastern Sudan to compare the epidemiology and clinical spectrum of Leishmania donovani infection in two populations differing in ethnic background and duration of residence in the area. The study took place in two villages from April 1994 to April 1996. In Um-Salala village, which is inhabited by members of the Masaleet tribe, half of the villagers had previous exposure to cutaneous leishmaniasis (Leishmaria major) before moving there. The population of the second village, Mushrau Koka, belong to the Hausa tribe and most were born there. The incidence of VL was 20.4/1000 person-years in 1994/1995 and increased sharply to 38.3/1000 person-years in 1995/1996 in Um-Salala. A rise in the incidence of VL was also observed in Mushrau Koka but with a lower incidence, 3.3/1000 person-years to 4.6/1000 person-years. The incidence rate of confirmed VL reflects only a limited part of the total infection rate which includes various forms of subclinical infection. The ratio of clinical to subclinical infection in Um-Salala was 1.2 : 1 in 1994/1995 compared with 2.6 : 1 in 1995/1996. This ratio was 1 : 11 in 1994/1995 and 1 : 2.5 in 1995/1996 in Mushrau Koka. In both villages the mean age of subclinical cases was higher, but in Mushrau Koka the mean age of subclinical cases also was higher than that of subclinical cases in Um-Salala. The leishmanin skin test (LST) was positive in 56% of individuals in Um-Salala and in 33% in Mushrau Koka. VL only occurred in leishmanin-negative individuals. Post kala-azar dermal leishmaniasis (PKDL) followed in 58% of confirmed VL patients in Um-Salala; the low incidence of VL for Mushrau Koka did not permit to estimate a PKDL rate. The clinical manifestations resulting from exposure to L. donovani range from subclinical infection to VL and PKDL. No firm conclusion as to the difference in incidence of VL between the two villages could be reached but differences in exposure to VL and cutaneous leishmaniasis (CL) as well as other factors such as ethnic background and differences in nutritional status may play a role.     

Humoral and cellular immune responses to glucose regulated protein 78 -- a novel Leishmania donovani antigen

The recently cloned glucose regulated protein 78 (GRP78) of Leishmania donovani has been suggested as a new and promising Leishmania vaccine candidate. We assessed antibody and T-cell reactivity to GRP78 in an enzyme-linked immunosorbent assay (ELISA) and in lymphoproliferative assays. Serological evaluation of plasma samples obtained in Sudan revealed that 89% of patients with visceral leishmaniasis (VL), 78% with post kala-azar dermal leishmaniasis (PKDL), and 85% with cutaneous leishmaniasis (CL) had antibody reactivity to this Leishmania antigen. Plasma from healthy Sudanese individuals living in an area endemic for malaria but free of leishmaniasis and plasma from healthy Danes was negative in the assay. GRP78 antibody was detected in 10% and 5% of plasma samples from Sudanese and Ghanaian malaria patients, respectively, whereas 35% of plasma samples from otherwise healthy Sudanese individuals with a positive leishmanin skin test showed antibody reactivity to recombinant GRP78 (rGRP78). In lymphoproliferative assays, 9 of 13 isolates of peripheral blood mononuclear cells (PBMC) from individuals previously infected with L. donovani and one of three individuals previously infected with L. major showed a response to rGRP78, whereas PBMC isolates from Danish control individuals did not respond. These findings, in addition to our previous observations in experimental CL (Jensen et al. 2001), confirm GRP78 as a possible vaccine antigen.     

Monoclonal antibodies against leishmanial membranes react with specific excreted factors (EF).

The interaction was examined between two reagents used for the speciation of Leishmania: spent culture-medium excreted factors (EF) and antileishmanial monoclonal antibodies (MCA). Thirty-three MCAs: seven against L. major, five against L. tropica, eight against L. aethiopica, 11 against L. donovani sensu lato and two against all Leishmania species were screened by double diffusion for reactions with EFs representing seven different sub-serotypes (A1,A2,A4,B1,B2,B3 and A3B2). Only five MCAs showed any reactivity. Three MCAs to L. major (T1, T2 and T7) precipitated only sub-serotype A1 and A4 EF, and two MCAs to L. tropica (T11 and T15) precipitated only sub-serotype A2 EF. Leishmania major and L. tropica are both serotype A species. None of the antiL. aethiopica and antiL. donovani MCAs reacted with any of the EF preparations. Both of these species belong to the serotype B. MCAs T11 and T15, the first recorded with a specificity for only sub-serotype A2 EF, were tested further against 28 sub-serotype A2 and three sub-serotype A2B2EFs from L. tropica strains. All 31 EFs formed visible bands with standard rabbit polyclonal antileishmanial serotype A serum. Only 18 of them precipitated with T11 and T15, even though parasite lysates prepared from promastigotes of several non-reactors tested positive with the MCAs. The lack of homogenous reactivity with T11 and T15 among the A2 EFs suggests that the EFs from these strains possess structural differences which affect EF-MCA precipitation.     

Cystatin C as a marker of immune complex-associated renal impairment in a Sudanese population with visceral leishmaniasis

Renal function was studied in visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL) by means of the specific marker cystatin C and related to circulating immune complexes and cytokine production. Forty patients with VL (23 with sub-acute disease and 17 with acute disease), 17 patients with PKDL, and 22 healthy controls were included. Cystatin C, but not creatinine, was significantly raised in VL (P = 0.004). The highest levels of cystatin C were found in those with acute disease (P < 0.0001). In VL, cystatin C levels were positively correlated to circulating immune complexes and production of granulocyte-macrophage colony stimulating factor (GM-CSF), but negatively correlated to aspartate aminotransferase and lactate dehydrogenase. We conclude that cystatin C is a superior marker of glomerular function in leishmaniasis and that immune complex deposition and GM-CSF are two functions that most likely are causally involved in the mechanisms leading to glomerular dysfunction in leishmaniasis.     

Successful miltefosine treatment of post-kala-azar dermal leishmaniasis occurring during antiretroviral therapy

The first two patients to be treated with miltefosine for post-kala-azar dermal leishmaniasis (PKDL) are reported. One was a 26-year-old Ethiopian man who had been treated with sodium stibogluconate, for relapsing visceral leishmaniasis (VL), four times between August 2002 and March 2004. In January 2004 this patient was found to be seropositive for HIV and began antiretroviral treatment with stavudine, lamivudine and nevirapine. Five months later he developed clinical PKDL, with extensive cutaneous, conjunctival and oral mucosal involvement. The second patient was a 42-year-old Ethiopian man who was treated for relapsing VL in November 2003. He too was subsequently found to be seropositive for HIV and was treated with stavudine, lamivudine and nevirapine from May 2004. He developed a nodular rash of PKDL over his face and upper body 2 weeks after starting the antiretroviral therapy. Treatment of both patients with oral miltefosine, at 100 mg/day for 28 days, led to the complete regression of their PKDL lesions. When checked 3-6 months after the end of the miltesofine treatment, neither patient showed any signs of VL, PKDL or other HIV-associated disease.     

The natural history of Sudanese post-kala-azar dermal leishmaniasis: clinical,immunological and prognostic features

In an exploration of the natural history of post-kala-azar dermal leishmaniasis (PKDL), 134 residents of Sudan who had recently been diagnosed as cases of the disease were investigated. In each case, diagnosis had been based on clinical criteria, the temporal relationship between the rash and the treatment of visceral leishmaniasis (VL), positive results in direct agglutination tests (DAT) and/or leishmanin skin tests (LST), and the exclusion of other skin conditions. The mean (S.D.) age of the subjects was 6.4 (3.0) years. Although PKDL appeared commonest among those aged 4-8 years (P < 0.05), it was most severe in children aged 相似文献   

Isoenzymatic variability of Leishmania infantum in Tunisia concerning 254 human strains

The different clinical forms of leishmaniasis are the result of both the immunological status of individuals and the species of the parasite causing the infection.

In Mediterranean countries, the Leishmania infantum complex groups zymodemes which are responsible for visceral, cutaneous and exceptionally cutaneomucosal or mucosal leishmaniasis.

We report in this study a synthesis concerning 254 cases of L. infantum that have been characterized at the “Laboratoire de Parasitologie” of the Rabta Hospital. The strains were isolated from human cases of visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL) by culture on NNN medium: 156 VL cases and 98 CL cases.

The isoenzymatic characterization revealed three zymodemes of L. infantum.

• L. infantum MON 1, a common zymodeme of VL, occurred in 154 cases (61%): 147 VL (95%) and 7 CL (5%). All CL cases were from the northern provinces, six of them occurring during an epidemic disease in 2001.

• L. infantum MON 24, a common zymodeme of CL in the north, occurred in 98 cases (38.5%): 91 CL (93%) and 7 VL (7%). The seven VL cases were immunocompetent children aged from 8 months to 9 years and native of northern Tunisia. Two of the CL cases were from central regions of the country. This is the first time that cases from these regions are reported.

• L. infantum MON 80, an uncommon zymodeme in Tunisia, occurred in two VL cases (0.5%): two children aged 7 and 5. The small number of strains of this zymodeme does not allow understanding of its epidemiological role.

The results of this study indicate a low enzymatic variability of L. infantum in the country. However, our study includes only human strains and should be extended to animal ones (dogs, rodents and sand flies). This would lead to a better understanding of the epidemiology of leishmaniasis in Tunisia.     

Leishmania tropica-isolated patient with visceral leishmaniasis in southern Iran

Visceral leishmaniasis (VL) is caused by various strains of Leishmania donovani, Leishmania infantum, and Leishmania chagasi with different geographical distribution. The aim of this study was to identify the strains of Leishmania that can cause VL in southern Iran. DNA of Leishmania were extracted from the slides of bone marrow aspirates (#42) and spleen punctures (#22), which were positive for leishman body from the patients who were referred to the hospitals affiliated with Shiraz University of Medical Sciences. Differences in Leishmania strains were determined by size difference of the polymerase chain reaction (PCR) amplification as visualized on agarose gel. PCR results and smears had 100% correlation. The dominant strain of Leishmania was L. infantum (63 out of the 64 cases), but one case of L. tropica was also detected. VL mostly involves children below 2 years of age in Iran, therefore infection with L. infantum was expected, but this study is the first report of VL that is caused by L. tropica in Iran.     

Post-kala-azar dermal leishmaniasis

Post-kala-azar dermal leishmaniasis (PKDL) is a complication of visceral leishmaniasis (VL); it is characterised by a macular, maculopapular, and nodular rash in a patient who has recovered from VL and who is otherwise well. The rash usually starts around the mouth from where it spreads to other parts of the body depending on severity. It is mainly seen in Sudan and India where it follows treated VL in 50% and 5-10% of cases, respectively. Thus, it is largely restricted to areas where Leishmania donovani is the causative parasite. The interval at which PKDL follows VL is 0-6 months in Sudan and 2-3 years in India. PKDL probably has an important role in interepidemic periods of VL, acting as a reservoir for parasites. There is increasing evidence that the pathogenesis is largely immunologically mediated; high concentrations of interleukin 10 in the peripheral blood of VL patients predict the development of PKDL. During VL, interferon gamma is not produced by peripheral blood mononuclear cells (PBMC). After treatment of VL, PBMC start producing interferon gamma, which coincides with the appearance of PKDL lesions due to interferon-gamma-producing cells causing skin inflammation as a reaction to persisting parasites in the skin. Diagnosis is mainly clinical, but parasites can be seen by microscopy in smears with limited sensitivity. PCR and monoclonal antibodies may detect parasites in more than 80% of cases. Serological tests and the leishmanin skin test are of limited value. Treatment is always needed in Indian PKDL; in Sudan most cases will self cure but severe and chronic cases are treated. Sodium stibogluconate is given at 20 mg/kg for 2 months in Sudan and for 4 months in India. Liposomal amphotericine B seems effective; newer compounds such as miltefosine that can be administered orally or topically are of major potential interest. Although research has brought many new insights in pathogenesis and management of PKDL, several issues in particular in relation to control remain unsolved and deserve urgent attention.     

Increased levels of interleukin-10 and IgG3 are hallmarks of Indian post-kala-azar dermal leishmaniasis

BACKGROUND: Post-kala-azar dermal leishmaniasis (PKDL), an established sequela of visceral leishmaniasis (VL), is proposed to facilitate anthroponotic transmission of VL, especially during interepidemic periods. Immunopathological mechanisms responsible for Indian PKDL are still poorly defined. METHODS: Our study attempted to characterize the immune profiles of patients with PKDL or VL relative to that of healthy control subjects by immunophenotyping, intracellular cytokine staining of peripheral blood mononuclear cells, and enzyme-linked immunosorbent assay for serum cytokines and immunoglobulin G (IgG) subclasses. RESULTS: Patients with PKDL had significantly raised percentages of peripheral CD3+CD8+ cells compared with control subjects, a difference that persisted after cure. Patients with PKDL showed an intact response to phytohemagglutinin, with the percentages of lymphocytes expressing interferon (IFN)-gamma, interleukin (IL)-2, IL-4, and IL-10 being comparable to those in control subjects. Patients with VL had decreased IFN-gamma and IL-2 expression, which was restored after cure, and increased IL-10 expression, which persisted after cure. In their response to Leishmania donovani antigen, patients with PKDL showed a 9.6-fold increase in the percentage of IL-10-expressing CD3+CD8+ lymphocytes compared with control subjects, and this percentage decreased with treatment. Patients with PKDL had raised levels of IgG3 and IgG1 (surrogate markers for IL-10), concomitant with increased serum levels of IL-10. CONCLUSIONS: IL-10-producing CD3+CD8+ lymphocytes are important protagonists in the immunopathogenesis of Indian PKDL.     

Amplified fragment length polymorphism (AFLP) analysis is useful for distinguishing Leishmania species of visceral and cutaneous forms

The Leishmania strains belonging to cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL) have been reported to possess close homology in genome profiles. To confirm this on genetic basis an attempt was made to differentiate Leishmania major; Leishmania tropica and Leishmania donovani genetically for the first time using amplified fragment length polymorphism (AFLP)—a high throughput DNA fingerprinting technique. The objective of this research work was to identify DNA markers of CL and VL. Ten combinations of selective primers detect a total of 1487 informative AFLP marker. Percentage of polymorphism was 45.12%. Three hundred and thirty-seven unique AFLP markers were also identified in three species of Leishmania. A clear distinction was revealed between L. major and L. donovani. It was inferred by AFLP analysis that a higher rate of polymorphisms occurred among Leishmania species which indicate the distinguished pattern of the disease cause by Leishmania, i.e. VL and CL. Analysis based on polymorphic AFLP markers revealed considerably high genetic variation among the genome of these species which was sufficient to distinguish between CL and VL.     

Molecular detection of Leishmania species in human and animals from cutaneous leishmaniasis endemic areas of Waziristan,Khyber Pakhtunkhwa,Pakistan

Objectives: To detect Leishmania species in human patients, animal reservoirs and Phlebotomus sandflies in Waziristan, Pakistan. Methods: Tissue smears and aspirates from 448 cutaneous leishmaniasis(CL) suspected patients were analyzed. To sort out role of the reservoir hosts, skin scrapings, spleen and liver samples from 104 rodents were collected. Furthermore, buffy coat samples were obtained from 60 domestic animals. Sandflies were also trapped. All human, animals and sandfly samples were tested by microscopy, kinetoplastic PCR and internal transcribed spacer 1(ITS1) PCR followed by restriction fragment length polymorphism for detection of Leishmania species. Results: An overall prevalence of 3.83% and 5.21% through microscopy and ITS1 PCR respectively was found. However, the statistically non-significant correlation was found between area, gender, and number of lesions. The presence of rodents, sandflies, domestic animals and internally displaced people increased the risk of CL. Using ITS1-PCR-RFLP, Leishmania tropica(L. tropica) was confirmed in 106 samples while 25 of the isolates were diagnosed as Leishmania major(L. major). Similarly, 3/104 rodents were positive for L. major and 14 pools of DNA samples containing Phlebotomus sergenti sandflies were positive for L. tropica. None of samples from domestic animals were positive for leishmaniasis. Conclusions: In the present study, L. tropica and L. major are found to be the main causative agents of CL in study area. Movement of internally displaced people from CL endemic areas presents a risk for nearby CL free areas. To the best of our knowledge, we report for the first time L. major infection in rodents(Rattus rattus) and L. tropica in Phlebotomus sergenti sandflies trapped in Waziristan, Pakistan.     

Identification and taxonomy of human and animal leishmanias by lectin-mediated agglutination

The surface polysaccharides of two strains of lizard leishmanias, of the guinea pig parasite L. enrietti and of nine strains of human leishmanias belonging to the groups mexicana, donovani and tropica were studied by lectin-mediated agglutination. Twenty-three lectins prepared from seeds or from higher fungi carpophores were used. They revealed the presence of L-fucose, N-N'-diacetylchitobiose, alpha-D-glucose, alpha-D-mannose, beta-D-galactose, N-acetyl-D-galactosamine and lactose. We noted a range in the number and variety of lectin receptor sites detectable on the surface of the leishmanias, with the reptiles strains having the fewest sites and the tropica group having the most sites. We were unable to find specific group lectins, but it seems possible to identify a strain within each group by a lectin-binding pattern.