American Cutaneous Leishmaniasis In Brazil Research Articles

Influence of Moonlight on Male Mating Aggregations of Nyssomyia whitmani, a Vector of American Cutaneous Leishmaniasis in Brazil

Nyssomyia whitmani (Antunes & Coutinho) is the sandfly vector of causative agents of American cutaneous leishmaniasis in South and Central America. It is widely spread throughout Brazil, in a close association with domestic animals. Almost nothing is known about male mating aggregations in N. whitmani, let alone the influence of moonlight on this behavior. Thus, the influence of moonlight on male N. whitmani aggregations was investigated by using non-attractant suction traps deployed in chicken cages under full moon and new moon nights. In this 18-night study, 2,160 specimens and seven species were collected. The most frequent species was N. whitmani accounting for 91.48% of the total sample. The abundance of males of N. whitmani was significantly higher in the presence than in the absence of moon. The sex ratio on new moon nights was 1:1 (M:F) and on full moon nights was male-biased (1.7:1). Based on this study, an influence of moonlight on male mating aggregations of N. whitmani was verified. The extent of this influence on increasing sandfly aggregation at hosts, the moonlight influence on the early flight activity of male sandflies and the use of chickens as aggregation sites for males of N. whitmani, are all discussed.

Toll-like receptors 2, 4, and 9 expressions over the entire clinical and immunopathological spectrum of American cutaneous leishmaniasis due to Leishmania (V.) braziliensis and Leishmania (L.) amazonensis

Leishmania (V.) braziliensis and Leishmania(L.) amazonensis are the most pathogenic agents of American Cutaneous Leishmaniasis in Brazil, causing a wide spectrum of clinical and immunopathological manifestations, including: localized cutaneous leishmaniasis (LCLDTH+/++), borderline disseminated cutaneous leishmaniasis (BDCLDTH±), anergic diffuse cutaneous leishmaniasis (ADCLDTH-), and mucosal leishmaniasis (MLDTH++++). It has recently been demonstrated, however, that while L. (V.) braziliensis shows a clear potential to advance the infection from central LCL (a moderate T-cell hypersensitivity form) towards ML (the highest T-cell hypersensitivity pole), L. (L.) amazonensis drives the infection in the opposite direction to ADCL (the lowest T-cell hypersensitivity pole). This study evaluated by immunohistochemistry the expression of Toll-like receptors (TLRs) 2, 4, and 9 and their relationships with CD4 and CD8 T-cells, and TNF-α, IL-10, and TGF-β cytokines in that disease spectrum. Biopsies of skin and mucosal lesions from 43 patients were examined: 6 cases of ADCL, 5 of BDCL, and 11 of LCL caused byL. (L.) amazonensis; as well as 10 cases of LCL, 4 of BDCL, and 6 of ML caused byL. (V.) braziliensis. CD4+ T-cells demonstrated their highest expression in ML and, in contrast, their lowest in ADCL. CD8+ T-cells also showed their lowest expression in ADCL as compared to the other forms of the disease. TNF-α+showed increased expression from ADCL to ML, while IL-10+and TGF-β+ showed increased expression in the opposite direction, from ML to ADCL. With regards to TLR2, 4, and 9 expressions, strong interactions of TLR2 and 4 with clinical forms associated with L. (V.) braziliensis were observed, while TLR9, in contrast, showed a strong interaction with clinical forms linked to L. (L.) amazonensis. These findings strongly suggest the ability of L. (V.) braziliensis and L. (L.) amazonensis to interact with those TLRs to promote a dichotomous T-cell immune response in ACL.

Environmental suitability for Lutzomyia (Nyssomyia) whitmani (Diptera: Psychodidae: Phlebotominae) and the occurrence of American cutaneous leishmaniasis in Brazil

BackgroundLeishmaniasis represents an important public health problem in Brazil. The continuous process of urbanization and expansion of human activities in forest areas impacts natural habitats, modifying the ecology of some species of Leishmania, as well as its vectors and reservoirs and, consequently, changes the epidemiological pattern that contributes to the expansion of American cutaneous leishmaniasis in Brazil. Here, we discuss Lutzomyia (Nyssomyia) whitmani, the main vector of ACL, transmitting two dermotropic Leishmania species including Leishmania (Viannia) braziliensis and Leishmania (V.) shawi.MethodsWe used the maximum entropy niche modelling approach (MaxEnt) to evaluate the environmental suitability of L. (N.) whitmani and the transmission of ACL in Brazil, in addition to designing models for a future scenario of climate change. MaxEnt was used under the “auto-features” mode and the default settings, with 100-fold repetition (bootstrap). The logistic output was used with higher values in the habitat suitability map, representing more favourable conditions for the occurrence of L. (N.) whitmani and human cases of ACL.ResultsTwo models were developed: the Lutzomyia (N.) whitmani model (LWM) and the American cutaneous leishmaniasis model (ACLM). LWM identified the species “preferential habitat” included regions with moderate annual precipitation (AP) between 1000–1600 mm, intermediate vegetation density (NDVI) values, mean temperature of the coldest quarter (MTCQ), between 15–21 °C, and annual mean temperature (AMT), between 19–24 °C. ACLM indicates that ACL is strongly associated with areas of intermediate density vegetation, areas with AP between 800–1200 mm, MTCQ above 16 °C and AMT below 23 °C.ConclusionsThe models generated for L. (N.) whitmani and ACL indicated a satisfactory predictive capacity. Future projections of LWM indicate an expansion of climatic suitability for L. (N.) whitmani for the northern and southern regions of Brazil. Future projections of ACL indicate the ongoing process of disease expansion in the face of the predicted climatic changes and reinforce the broad geographical expanse of this disease in Brazil. The models were able to identify that a continuous process of environmental degradation favours the establishment of L. (N.) whitmani and the occurrence of ACL by a strong association of the vector(s) and ACL to areas of intermediate vegetation cover density.

Cutaneous leishmaniasis in northeastern Brazil: a critical appraisal of studies conducted in State of Pernambuco

American cutaneous leishmaniasis (ACL) is a complex disease with clinical and epidemiological features that may vary from region to region. In fact, at least seven different Leishmania species, including Leishmania (Viannia) braziliensis, Leishmania (Viannia) guyanensis, Leishmania (Viannia) lainsoni, Leishmania (Viannia) naiffi, Leishmania (Viannia) shawi, Leishmania (Viannia) lindenbergi, and Leishmania (Leishmania) amazonensis, have been implicated in the etiology of ACL in Brazil, and numerous phlebotomine sandfly species of the genus Lutzomyia have been regarded as putative or proven vectors. Because ACL is a focal disease, understanding the disease dynamics at the local level is essential for the implementation of more effective control measures. The present paper is a narrative review about the ACL epidemiology in Pernambuco, northeastern Brazil. Furthermore, the need for more effective diagnosis, treatment, control and prevention strategies for the affected populations is highlighted. This paper will provide researchers with a critical appraisal of ACL in Pernambuco. Hopefully, it will also be helpful for public health authorities to improve current control strategies against ACL at the state and country levels.

Comparative analysis of the geographic distribution of the histopathological spectrum and Leishmania species of American cutaneous leishmaniasis in Brazil

Knowledge of the relationship between specific geographical differences and histopathology of the American cutaneous leishmaniasis is limited because host-parasite interactions in space and time are complex. To describe the geographic analysis of the histopathological pattern of localized American cutaneous leishmaniasis and the relationship with Leishmania species. A cross-sectional, descriptive and analytical study of a sample consisting of 55 patients of municipal districts of Montes Claros and 32 of Caratinga, Minas Gerais, by comparing with other endemic regions in Brazil, assessing historical and microregional data and developing confidence intervals. A preponderance of cellular exudative reactions in the cutaneous form of American cutaneous leishmaniasis was found in the municipal districts of Caratinga, east of Minas Gerais, Montes Claros, north of Minas Gerais and Uberlândia, Triangulo Mineiro, and also in the states of Mato Grosso and Ceara. Necrotic and exudative granulomatous reactions were found to be more frequent in the northern areas, mainly in the states of Amazonas and Para. Necrotic and exudative reactions were the most frequent form of presentation found throughout Brazil when the predominance of L. braziliensis was below 90% in relation to other species. There is a geographic variation of the immune inflammatory response in American cutaneous leishmaniasis. Geographical correlations between the predominant species of Leishmania and the most frequent forms of histopathological presentation of American cutaneous leishmaniasis, which until the present study had not been performed, enables new approaches to the study of Leishmania subpopulations in areas with a predominance of one species and provides evidence of variations in the biological behavior of different species.

The Vectorial Potential ofLutzomyia (Nyssomyia) intermediaandLutzomyia (N.) whitmaniin the Transmission ofLeishmania (V.) braziliensisCan Also Be Related to Proteins Attaching

We read with great interest the report by Soares et al. [1] on the potential of Leishmania (Viannia) braziliensis to attach to the midgut of the sand flies Lutzomyia (N.) whitmani and Lutzomyia (N.) intermedia. This manuscript assesses relevant information concerning the biomolecular phenomena between Leishmania promastigotes and the midgut of Lutzomyia species that act as vectors of American Cutaneous Leishmaniasis (ACL). However, it is necessary to comment that the basis of these physiological processes is not directly driven by glycolipid lipophosphoglycan (LPG) only. Other L. (V.) braziliensis promastigotes surface components, as proteins, can also be implicated in many steps of the midgut attachment. Since 2007 we have been investigating the potential of heparin binding proteins (HPBs) from L. (V.) braziliensis promastigotes in the attachment of parasites to gut proteins from L. (N.) intermedia and L. (N.) whitmani [2]. We have indicated the existence of physicochemical conditions for the binding between the gut proteins from Lutzomyia spp. and the HPBs—a new macromolecule class involved in the recognition of the sand fly gut epithelium by L. (V.) braziliensis. We proposed that the five HPB ligands (67.0, 62.1, 59.5, 56.0, and 47.5 kDa) observed in both L. (N.) intermedia and L. (N.) whitmani are involved with the promastigote attachments to sand fly gut epithelium. Also, we suggested that the physicochemical conditions for the interaction between HBP and their ligands are more favourable in the midgut of L. (N.) whitmani than in L. (N.) intermedia. Furthermore, heparin similar molecules, synthesized by cells of midgut epithelium seem to act as anchoring sites for L. (V.) braziliensis promastigotes. The ability of promastigotes to adhere to epithelial microvillii of the Phlebotominae digestorium tube is an essential stage for the maintenance of the parasite life cycle, being a factor of distinction between infective and noninfective stains. Similarly to LPG, the HBPs are related to the infective forms of the parasite [3, 4]. In such a way, its presence can be an essential factor for the setting of promastigotes in the digestorium tube and for the continuity of the life cycle, since parasites unable to adhere to the intestinal epithelium would be rejected together with the “feces” of the insect vector [5]. In addition, L. (N.) intermedia and L. (N.) whitmani are related to L. (V.) braziliensis transmission in the same endemic area [6]. The detection of ligands with similar molecular weights in the digestorium tube of both insect species is a biochemical indicative of vectorial homogeneity of these species in the transmission of ACL. The mapping of the interactions between molecules from both parasite and vector molecules can help in the understanding of adhesion to epithelial cells through the parasite surface. Thus, our results considered together with the recent findings by Soares et al. [1] present biochemical indicatives of the epidemiological relevance of L. (N.) whitmani as a primary vector of ACL in Brazil.

Proven and putative vectors of American cutaneous leishmaniasis in Brazil: aspects of their biology and vectorial competence

The aim of the present review is to give relevant information on aspects of the biology and ecology, including the vectorial competence of Lutzomyia sand fly species suggested as vectors of American cutaneous leishmaniasis in Brazil. The disease, due to Leishmania (Viannia) braziliensis, has been registered in most municipalities in all the Brazilian states and its transmission is associated with more than one sand fly species in each geographical region. A variety of Leishmania species can be found in the Amazon basin, where different epidemiological chains have been detected with the participation of different phlebotomine vectors. Finally, a discussion is presented on some sand fly species found naturally infected by Leishmania, but for which there is as yet no evidence regarding their epidemiological importance.

<![CDATA[<B><I>Lutzomyia (Nyssomyia) whitmani s.l </I>. (Antunes & Coutinho, 1939)(Diptera: Psychodidae: Phlebotominae)</B>: <B>geographical distribution and the epidemiology of American cutaneous leishmaniasis in Brazil Mini-review</B>]]>

The aim of the present study, in view of the widespread geographical distribution of Lutzomyia (Nyssomyia) whitmani s.l. in Brazil, in close association with the regions of transmission of Leishmania (Viannia) braziliensis and L. (V.) shawi, is to investigate the distribution of this sand fly species and American cutaneous leishmaniasis (ACL) in relationship to vegetation and landscape ecology throughout Brazil. Thematic maps were elaborated by the MapInfo programme, giving information on the spatial distribution of L. whitmani s.l., in accordance with types of vegetation and foci of ACL. With regards to the known areas of transmission of ACL in Brazil, it is notable that L. (N.) whitmani s.l. occurs in most of them, where it has been implicated as a possible vector of L. (V.) braziliensis. The presence of L. whitmani s.l. has been registered in 26 states, the one exception being Santa Catarina; in some states such as Roraima, Acre, Tocantins, and Mato Grosso do Sul this sand fly species has been recorded in a large number of municipalities. L. whitmani s.l. has been found in association with a variety of vegetation types, including the Amazonian forest, savanna ("campos cerrados"), and northeastern savanna ("caatingas nordestinas" or "savana estépica").

Lutzomyia (Nyssomyia) whitmani s.l . (Antunes & Coutinho, 1939)(Diptera: Psychodidae: Phlebotominae): geographical distribution and the epidemiology of American cutaneous leishmaniasis in Brazil Mini-review

The aim of the present study, in view of the widespread geographical distribution of Lutzomyia (Nyssomyia) whitmani s.l. in Brazil, in close association with the regions of transmission of Leishmania (Viannia) braziliensis and L. (V.) shawi, is to investigate the distribution of this sand fly species and American cutaneous leishmaniasis (ACL) in relationship to vegetation and landscape ecology throughout Brazil. Thematic maps were elaborated by the MapInfo programme, giving information on the spatial distribution of L. whitmani s.l., in accordance with types of vegetation and foci of ACL. With regards to the known areas of transmission of ACL in Brazil, it is notable that L. (N.) whitmani s.l. occurs in most of them, where it has been implicated as a possible vector of L. (V.) braziliensis. The presence of L. whitmani s.l. has been registered in 26 states, the one exception being Santa Catarina; in some states such as Roraima, Acre, Tocantins, and Mato Grosso do Sul this sand fly species has been recorded in a large number of municipalities. L. whitmani s.l. has been found in association with a variety of vegetation types, including the Amazonian forest, savanna ("campos cerrados"), and northeastern savanna ("caatingas nordestinas" or "savana estépica").

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, Petropolis 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.

Characterization of Leishmania sp. strains isolated from autochthonous cases of human cutaneous leishmaniasis in Santa Catarina State, southern Brazil

Four Leishmania sp. samples were isolated from autochthonous human cases of American cutaneous leishmaniasis (ACL) in Santa Catarina State, southern Brazil. These strains were characterized using indirect immunofluorescence with a panel of Leishmania-specific monoclonal antibodies (MAbs), and by PCR amplification and hybridization assay of the mini-exon gene with group specific probes. The results obtained with the MAbs were in agreement with the genetic marker. Two isolates (MHOM/BR/89/JSC89-H1 and MHOM/BR/89/JSC89-H2) were identified as L. (Leishmania) amazonensis and two (MHOM/BR/96/LSC96-H3 and MHOM/BR/97/LSC97-H4) as L. (Viannia) braziliensis. The southernmost autochthonous cases of ACL in Brazil are due to two different Leishmania sp. species, confirming the spreading of ACL on the American continent.

A new enzymatic variant of Leishmania (Leishmania) forattinii isolated from Proechimys iheringi (Rodentia, Echimydae) in Espírito Santo, Brazil.

Taxonomic studies of leishmanial isolates fromthe New World indicate tremendous diversitywithin this genus (E Cupolillo et al. 1994 Am JTrop Med Hyg 50: 296-311). A number of newLeishmania species from sylvan areas of theNeotropics have been described recently. Some ofthose parasites are associated with disease in hu-mans; others appear to be restricted to lower or-ders of mammals, such as rodents and edentates(G Grimaldi et al. 1989 Am J Trop Med Hyg 41:687-725). However, some of the latter parasitesmay yet be shown capable of causing human dis-ease, particularly in persons with altered cellularimmune responses.During a survey of potential reservoir hosts ofLeishmania done in the State of Espirito Santo, Bra-zil (1982-1985), three leishmanial parasites (des-ignated with stock codes MPRO/BR/82/RV203,MPRO/BR/82/RV228, and MPRO/BR/85/RV260)were isolated from skin lesion samples taken fromspiny-rats, Proechimys iheringi (Rodentia,Echimydae), captured in a secondary forest locatedin the municipality of Viana (A Falqueto et al. 1985Mem Inst Oswaldo Cruz 80: 497). In studies us-ing an indirect radioimmune binding assay (RIA)and a large panel of monoclonal antibodies (Mabs)derived for selected species of Leishmania , the iso-lates were characterized as members of the L.mexicana complex. These strains were differentfrom those species infective to humans, in that theyreacted with either the L.(L.) amazonensis or L.(L.) mexicana specific MAbs. Furthermore, thiswas also the case with cloned organisms from twostocks showing that they were not mixed popula-tions of Leishmania (G Grimaldi et al. 1987 Am JTrop Med Hyg 36: 270-287). This group of dis-tinct parasites presented, however, similarserodeme patterns in relation to the new recentlydescribed species of the Leishmania subgenus, L.(L.) forattinii (E Yoshida et al. 1993 Mem InstOswaldo Cruz 88: 397-406).The latter parasite was isolated from sylvaticreservoir hosts (Didelphis marsupialis aurita andP. iheringi denigratus ) captured on regions endemicfor American cutaneous leishmaniasis in Brazil,respectively in the municipalities of Conchas, SaoPaulo (E Yoshida et al. 1979 Rev Inst Med Trop SPaulo 21: 110-113) and Tres Bracos, Bahia (ABarreto et al. 1985 Rev Soc Bras Med Trop 18:243-246). The general morphology and the growthcharacteristics in vitro of the new species were simi-lar to those of other L. mexicana complex para-sites. Here we have further studied the Espirito Santoisolates using additional techniques for the char-acterization of Leishmania . The molecular proce-dures used for typing the strains (isoenzyme elec-trophoresis, blot enzyme binding assay usingMAbs, restriction endonuclease fragment patternsof k-DNA, and molecular karyotype analysis) havebeen described in detail in previous publications(Yoshida et al. 1979, 1983 loc. cit. , Cupolillo et al.1994 loc. cit., A Franco et al. 1997 Mem InstOswaldo Cruz 92: 63-68).Results of electrophoretic analysis were basedon the following enzymatic loci, namely: glucose-6-phosphate dehydrogenase (G6PDH), malate de-hydrogenase (MDH), isocitrate dehydrogenase(IDHNADP), 6-phosphogluconate dehydrogenase(6PGDH), nucleotidase (NH1 and NH2), glucosephosphate isomerase (GPI), phosphoglucomutase(PGM), proline dipeptidase (PEPD), leucine pep-tidase (PEP2), malic enzyme (ME), mannose phos-phate isomerase (MPI), and aconitate hydratase(ACON). The enzyme profiles of the selected iso-lated signature MPRO/BR/82/RV228, which rep-resents the poorly defined group of parasites from