Clinical picture of cutaneous leishmaniases due to Leishmania (Leishmania) mexicana in the Yucatan peninsula, Mexico

Localized cutaneous leishmaniasis (LCL), known as "chiclero's ulcer" in southeast Mexico, was described by Seidelin in 1912. Since then, the sylvatic region of the Yucatan peninsula has been identified as an endemic focus of LCL. The purpose of the present work was to describe the clinical picture of LCL caused by Leishmania (Leishmania) mexicana in the Yucatan peninsula. A total of 136 cases of LCL, based on isolation and characterization of L. (L.) mexicana by isoenzymes and/or monoclonal antibodies, were selected. Some variability of clinical features regarding number, type, size, form, location and time of evolution of the lesions was observed. The most frequently observed presentation was a single, ulcerated, rounded small lesion, located on the ear, with an evolution time of less than three months, with neither cutaneous metastases nor lymphatic nor mucosal involvement. This picture corresponds to previous studies carried out in the same endemic area where an organism of the L. mexicana complex has been incriminated as a major aetiological agent of classical "chiclero's ulcer", confirming that in the Yucatan peninsula LCL due to L. (L.) mexicana when located on the pinna of the ear is a remarkable characteristic.

Distribution of sand flies (Diptera: Psychodidae) at different altitudes in an endemic region of American cutaneous leishmaniasis in the State of Espírito Santo, Brazil

The involvement of different sand fly species in the transmission of American cutaneous leishmaniasis (ACL) at different altitudes was evaluated in the municipality of Afonso Cláudio in the State of Espírito Santo, Brazil, from November 1995 to February 1997. CDC light traps and Shannon traps baited with human volunteers were hung simultaneously at three altitudes of a river valley: (a) 650-750 m in an area of active ACL transmission; (b) 750-850 m in a transitional area; and (c) 850-950 m in an area where no ACL transmission occurred. A total of 13,363 specimens belonging to 28 species was collected. The five most abundant man-biting species were Lutzomyia intermedia, which constituted 24.3% of the total, Lu. migonei (22.3%), Lu. whitmani (15.4%), Lu. fischeri (14.9%) and Lu. monticola (5.8%). Analysis of the distribution of these species at the three altitudes provided evidence that Lu. fischeri and Lu. monticola were not involved in ACL transmission, whereas Lu. migonei and Lu. whitmani might act as secondary vectors of Leishmania (Viannia) braziliensis and Lu. intermedia was probably the principal vector of the parasite. These results reinforce those published in the existing literature, which indicate that Lu. intermedia is the main vector of Le. (V.) braziliensis in Southeast Brazil, while Lu. migonei and Lu. whitmani are of secondary importance.

Muco-cutaneous leishmaniasis in the New World: The ultimate subversion.

Infection by the human protozoan parasite Leishmania can lead, depending primarily on the parasite species, to either cutaneous or mucocutaneous lesions, or fatal generalized visceral infection. In the New World, Leishmania (Viannia) species can cause mucocutaneous leishmaniasis (MCL). Clinical MCL involves a strong hyper-inflammatory response and parasitic dissemination (metastasis) from a primary lesion to distant sites, leading to destructive metastatic secondary lesions especially in the nasopharyngal areas. Recently, we reported that metastasizing, but not non-metastatic strains of Leishmania (Viannia) guyanensis, have high burden of a non-segmented dsRNA virus, Leishmania RNA Virus (LRV). Viral dsRNA is sensed by the host Toll-like Receptor 3 (TLR3) thereby inducing a pro-inflammatory response and exacerbating the disease. The presence of LRV in Leishmania opens new perspectives not only in basic understanding of the intimate relation between the parasite and LRV, but also in understanding the importance of the inflammatory response in MCL patients.

Presence of American cutaneous leishmaniasis vectors surrounding the city of Medellín, Colombia

The presence of Lutzomyia (Helcocyrtomyia) hartmanni, as a vector of Leishmania colombiensis and L. columbiana (Verrucarum group), recently incriminated in the transmission of leishmaniasis, and L. pia (Verrucarum group) are reported for the first time in a periurban area of Medellín city. There is thus a risk of leishmaniasis transmission in this town.

Concurrent cutaneous, visceral and ocular leishmaniasis caused by Leishmania (Viannia) braziliensis in a kidney transplant patient

Although cases of leishmaniasis co-infection have been described in acquired immunodeficiency syndrome patients as well as those who have undergone organ transplants, to our knowledge, the present report is the first documented case of simultaneous cutaneous, visceral and ocular leishmaniasis due to Leishmania (Viannia) braziliensis in a transplant patient. The patient had been using immunosuppressive drugs since receiving a transplanted kidney. The first clinical signs of leishmaniasis included fever, thoracic pain, hepatosplenomegaly, leucopenia and anemia. The cutaneous disease was revealed by the presence of amastigotes in the skin biopsy. After three months, the patient presented fever with conjunctive hyperemia, intense ocular pain and low visual acuity. Parasites isolated from iliac crest, aqueous humor and vitreous body were examined using a range of molecular techniques. The same strain of L. (V.) braziliensis was responsible for the different clinical manifestations. The immunosuppressive drugs probably contributed to the dissemination of Leishmania.

Seasonality of Lutzomyia intermedia and Lutzomyia whitmani (Diptera: Psychodidae: Phlebotominae), occurring sympatrically in area of cutaneous leishmaniasis in the State of Rio de Janeiro, Brazil

Lutzomyia intermedia and Lutzomyia whitmani occur sympatrically in the district of Posse, municipality of Petrópolis, in the State of Rio de Janeiro (114 km from the city of Rio de Janeiro), where sand flies were captured weekly for three consecutive years in both the peridomicile and forest, in two first years from 18:00 to 22:00 h, using a Shannon trap and CDC light traps. The anthropophilic habit was assessed by recording the specimens that bit the human captors. Considering the different capture types and sites, the following species were identified: Brumptomyia brumpti, B. cardosoi, B. guimaraesi, Lutzomyia amarali, L. longipalpis, L. microps, L. costalimai, L. edwardsi, L. firmatoi, L. migonei, L. termitophila, L. tupynambai, L. fischeri, L. pessoai, L. lutziana, L. shannoni, L. barrettoi, L. intermedia, L. whitmani, L. lloydi, and L. minasensis. L. intermedia (38.3%) and L. whitmani (38.6%) predominated. L. intermedia predominated in the peridomicile, where it displayed more intense anthropophily, while L. whitmani displayed greater density in the banana plantations and forest, preferential sites for biting humans. Studies on seasonality showed that while L. intermedia displayed greater density in the hottest months of the year (December, January, and February), L. whitmani was abundant in the coolest months (June, July, and August), although both occurred throughout the year.

B-cell infiltration and frequency of cytokine producing cells differ between localized and disseminated human cutaneous leishmaniases

Biopsies from human localized cutaneous lesions (LCL n = 7) or disseminated lesions (DL n = 8) cases were characterized according to cellular infiltration,frequency of cytokine (IFN-g, TNF-alpha) or iNOS enzyme producing cells. LCL, the most usual form of the disease with usually one or two lesions, exhibits extensive tissue damage. DL is a rare form with widespread lesions throughout the body; exhibiting poor parasite containment but less tissue damage. We demonstrated that LCL lesions exhibit higher frequency of B lymphocytes and a higher intensity of IFN-gamma expression. In both forms of the disease CD8+ were found in higher frequency than CD4+ T cells. Frequency of TNF-alpha and iNOS producing cells, as well as the frequency of CD68+ macrophages, did not differ between LCL and DL. Our findings reinforce the link between an efficient control of parasite and tissue damage, implicating higher frequency of IFN-gamma producing cells, as well as its possible counteraction by infiltrated B cells and hence possible humoral immune response in situ.

Recent observations on the sand fly (Diptera: Psychodidae) fauna of the State of Rondônia, Western Amazônia, Brazil: the importance of Psychdopygus davisi as a vector of zoonotic cutaneous leishmaniasis

Sand flies were collected in the central region of the state of Rondônia (W 64º30' to 63º00' and S 10º00'to 11º00') using Shannon and CDC light traps from October 1997 to August 2000. A total of 85,850 specimens representing 78 named species were captured. Of these 14 were new records for Rondônia. The proportion of males/females was 1/1.131. Trypanosomatids, that are presently being identified, were detected in 11 species. Leishmania (Viannia) naiffi was recorded from Psychodopygus davisi and P. hirsutus. In the present study the dominant species was P. davisi (39.6%) followed by Lutzomyia whitmani (13.1%), P. carrerai (11.6%), and P. hirsutus (10.2%). The importance of P. davisi as a vector of zoonotic cutaneous leishmaniasis is discussed.

Epidemiological and clinical features of Leishmania (Viannia) braziliensis American cutaneous and mucocutaneous leishmaniasis in the State of Espírito Santo, Brazil

Between 1985 and 2000, epidemiological surveys of the American tegumentary leishmaniasis (ATL) were carried out in several rural and urban communities in Espírito Santo, Brazil. A total of 100 stocks of Leishmania (comprising isolates from both human and canine hosts with ATL) were identified by two methods of molecular characterization, using specific monoclonal antibodies and multilocus enzyme electrophoresis. Parasite isolates from 19 municipalities were found to belong to the same zymodeme and serodeme type as of the Leishmania (Viannia) braziliensis reference strain. In contrast, our genotyping studies have shown intra-specific variation among these parasites (comparisons of the variability of the internal transcribed spacers between the small and large subunits of the rRNA genes of the 22 stocks studiedrevealed at least 11 genotypes). Two main clusters of L. (V.) braziliensis genotypes were observed, representing parasites collected from different endemic regions in the state, where transmission reflects distinct eco-epidemiological features. Infection with this pathogen was associated with the characteristic disease forms, but neither the clinical outcome nor the response to treatment could be related to the genetic polymorphism of the isolates, as defined by using the proposed methodology.

Therapy of Venezuelan patients with severe mucocutaneous or early lesions of diffuse cutaneous leishmaniasis with a vaccine containing pasteurized Leishmania promastigotes and bacillus Calmette-Guerin: preliminary report

Severe mucocutaneous (MCL) and diffuse (DCL) forms of American cutaneous leishmaniasis (ACL) are infrequent in Venezuela. Chemotherapy produces only transitory remission in DCL, and occasional treatment failures are observed in MCL. We have evaluated therapy with an experimental vaccine in patients with severe leishmaniasis. Four patients with MCL and 3 with early DCL were treated with monthly intradermal injections of a vaccine containing promastigotes of Leishmania (Viannia) braziliensis killed by pasteurization and viable Bacillus Calmette- Guerin. Clinical and immunological responses were evaluated. Integrity of protein constituents in extracts of pasteurized promastigotes was evaluated by gel electrophoresis. Complete remission of lesions occurred after 5-9 injections in patients with MCL or 7-10 injections in patients with early DCL. DCL patients developed positive skin reactions, average size 18.7 mm. All have been free of active lesions for at least 10 months. Adverse effects of the vaccine were limited to local reactivity to BCG at the injection sites and fever in 2 patients. Extracts of pasteurized and fresh promastigotes did not reveal differences in the integrity of protein components detectable by gel electrophoresis. Immunotherapy with this modified vaccine offers an effective, safe option for the treatment of patients who do not respond to immunotherapy with vaccine containing autoclaved parasites or to chemotherapy .

Clinical and immunopathological spectrum of American cutaneous leishmaniasis with special reference to the disease in Amazonian Brazil: a review

The wide variety of Leishmania species responsible for human American cutaneous leishmaniasis combined with the immune mechanisms of the host results in a large spectrum of clinical, histopathological, and immunopathological manifestations. At the middle of this spectrum are the most frequent cases of localized cutaneous leishmaniasis (LCL) caused by members of the subgenera Leishmania and Viannia, which respond well to conventional therapy. The two pathogenicity extremes of the spectrum generally recognized are represented at the hypersensitivity pole by mucocutaneous leishmaniasis (MCL) and at the hyposensitivity pole by anergic diffuse cutaneous leishmaniasis (ADCL). Following the present study on the clinical, histopathological and immunopathological features of cutaneous leishmaniasis in Amazonian Brazil, we propose the use of the term "borderline disseminated cutaneous leishmaniasis" for the disseminated form of the disease, due to parasites of the subgenera Leishmania and Viannia, which might be regarded as intermediate between LCL and the extreme pathogenicity poles MCL and ADCL.

Moonlight and blood-feeding behaviour of Lutzomyia intermedia and Lutzomyia whitmani (Diptera:Psychodidae:Phlebotominae), vectors of American cutaneous leishmaniasis in Brazil

Lutzomyia intermedia (Lutz & Neiva, 1912) and L. whitmani (Antunes & Coutinho, 1939) (Diptera: Psychodidae: Phlebotominae), two important vectors of American cutaneous leishmaniasis in Brazil, occur in sympatry in the locality of Posse county, Petrópolis municipality, state of Rio de Janeiro, Brazil. We investigated the influence of the lunar cycle on the frequency of specimens of the two species caught while attempting to bite the collectors and in CDC light traps. Analysis of the numbers of sand flies captured in different lunar phases for two consecutive years in the peridomestic site and forest shows that there is a significant positive correlation between moonlight intensity and the numbers of L. intermedia and L. whitmani females collected while blood-feeding, whereas the opposite was observed for the CDC traps.

Multiplex-PCR for detection of natural Leishmania infection in Lutzomyia spp. captured in an endemic region for cutaneous leishmaniasis in state of Sucre, Venezuela

We studied the natural infection of Lutzomyia (Lutzomyia) sp. with Leishmania in endemic foci of cutaneous leishmaniasis in the Paria peninsula, state of Sucre, Venezuela. Sand flies were collected between March 2001 and June 2003, using Shannon light-traps and human bait. Of the 1291 insects captured, only two species of phlebotomines were identified: L. ovallesi (82.75%) and L. gomezi (17.42%). A sample of the collected sand flies (51 pools of 2-12 individuals) were analyzed by using a multiplex-PCR assay for simultaneous detection of New Word Leishmaniaand Viannia subgenera. The results showed a total of 8 pools (15.68%) infected; of these, 7 were L. ovallesi naturally infected with L. braziliensis (2 pools) and L. mexicana (5 pools) and 1 pool of L. gomezi infected by L. braziliensis.

Further observations on clinical, histopathological, and immunological features of borderline disseminated cutaneous leishmaniasis caused by Leishmania (Leishmania) amazonensis

Leishmania (Leishmania) amazonensis has for some time been considered as the causative agent of two distinct forms of American cutaneous leishmaniasis (ACL): localized cutaneous leishmaniasis (LCL), and anergic diffuse cutaneous leishmaniasis (ADCL). Recently, a new intermediate form of disease, borderline disseminated cutaneous leishmaniasis (BDCL), was introduced into the clinical spectrum of ACL caused by this parasite, and in this paper we record the clinical, histopathological, and immunological features of eight more BDCL patients from Brazilian Amazonia, who acquired the disease in the Pará state, North Brazil. Seven of them had infections of one to two years' evolution and presented with primary skin lesions and the occurrence of metastases at periods varying from six to 12 months following appearance of the first lesion. Primary skin lesions ranged from 1-3 in number, and all had the aspect of an erythematous, infiltrated plaque, variously located on the head, arms or legs. There was lymphatic dissemination of infection, with lymph node enlargement in seven of the cases, and the delayed hypersensitivity skin-test (DTH) was negative in all eight patients prior to their treatment. After that, there was a conversion of DTH to positive in five cases re-examined. The major histopathological feature was a dermal mononuclear infiltration, with a predominance of heavily parasitized and vacuolated macrophages, together with lymphocytes and plasma cells. In one case, with similar histopathology, the patient had acquired his infection seven years previously and he presented with the largest number of disseminated cutaneous lesions. BDCL shows clinical and histopathological features which are different from those of both LCL and ADCL, and there is a good prognosis of cure which is generally not so in the case of frank ADCL.

Dispersal pattern of the sand fly Lutzomyia neivai (Diptera: Psychodidae) in a cutaneous leishmaniasis endemic rural area in Southeastern Brazil

The dispersal pattern of the sand fly Lutzomyia neivai was studied through mark-release-recapture experiments in an American cutaneous leishmaniasis endemic rural area in Southeastern Brazil. Over 6500 specimens were marked with fluorescent powder and released in forest edge and peridomicile habitats from August to November 1999, February and April 2000. Recapture attempts were made using Shannon and CDC traps up to eight successive nights after releases. A total of 493 (7.58%) specimens were recaptured. The number of recaptured males and females of L. neivai in CDC traps was not affected by the distance between the trap and the release points. Approximately 90% of males and females recaptured in CDC traps were caught up to 70 m from the release points. The maximum female flight range recorded was 128 m. The average flight range per day was less than 60 m for males and females. Of the flies released in forest edge, approximately 16% of the recaptured females were caught in Shannon traps in the peridomicile habitat. The results indicate that the movements of L. neivai are spatially focal and the possibility of dispersion from forest to peridomicile habitat may be an important way of contracting leishmaniasis in dwellings.