The effect of antireaction medications on the association between periodontitis and leprosy reactions: An important methodological issue in periodontal medicine.

BACKGROUND: The treatment of leprosy reactions (LRs) involves thalidomide, corticosteroids, and other immunomodulatory medications. This study evaluated the effect of these treatments on the association between periodontitis and LRs, as well as factors associated with LRs. METHODS: This case-control study was conducted on 283 individuals followed at a leprosy outpatient clinic in Brazil. The case group was comprised of 158 individuals presenting type 1 or type 2 LRs, and the control group of 125 leprosy individuals without reactions. A complete oral examination was performed to diagnose periodontitis, the independent variable. Antireaction medication used was collected from medical records, and participants were classified according to the use of prednisone and/or thalidomide, time of use, or non-use of medication. Socioeconomic-demographic, clinical, and lifestyle covariables were collected by interview. Unconditional logistic regression analysis by subgroups evaluated the effect of antireaction medication on the association between periodontitis and LRs, estimating the odds ratio with a 95% confidence interval (OR; 95% CI). RESULTS: A relationship between periodontitis and LRs was observed only in the subgroup using the association prednisone and thalidomide: ORadjusted = 0.32; 95% CI = 0.11-0.95. Conversely, more severe periodontal clinical parameters were observed in cases versus controls. Several socioeconomic, health conditions, and lifestyle factors were associated with the presence of LRs. CONCLUSIONS: Although periodontal disease indicators were worse among the cases, the findings showed a negative relationship between periodontitis and LRs in individuals receiving associated prednisone and thalidomide. These medications appear to influence the inflammatory cascade between diseases, modifying and masking the manifestations of periodontitis.

Clinical profile of vitiligo patients and relationship with immuno-inflammatory markers.

BACKGROUND: Vitiligo is the most common pigmentary disorder and is considered a chronic, cumulative, multifactorial disease. The crucial role of cytotoxic CD8+ T lymphocytes and the IFNγ/CXCL10 axis has been demonstrated in its pathogenesis. OBJECTIVE: To evaluate the clinical profile and immuno-inflammatory markers in patients with vitiligo in a reference medical center. METHODS: Cross-sectional study in which all patients with vitiligo seen at the medical center the from 2019 to 2022 were evaluated, to outline the clinical profile. Moreover, cardiovascular risk biomarkers (neutrophil/lymphocyte ratio and C-reactive protein levels) were measured, as well as cytokines and chemokines (TNFα, IFNγ, IL10, IL15 and CXCL10) in the serum of a subgroup of 30 patients. RESULTS: There was a predominance of females, with a mean age of 43 years. Most were phototypes IV or V (71.3%), without comorbidities (77.55%), and without a family history of vitiligo (70.41%). Higher levels of neutrophil/lymphocyte ratio, C-reactive protein, and inflammatory cytokines/chemokines were documented in vitiligo patients when compared to the control group (non-significant). As relevant data, the highest values of CXCL10 were detected in patients with vitiligo versus controls, as well as in patients with disease of shorter duration (p<0.05). STUDY LIMITATIONS: The number of assessed patients was small due to recruitment difficulties caused by the COVID-19 pandemic. CONCLUSION: The present data contribute to confirming the relevant role of the IFNγ/CXCL10 axis in the pathogenesis of vitiligo, highlighting CXCL10 as a possible activity marker.

Clinical profile of vitiligo patients and relationship with immuno-inflammatory markers

Abstract Background Vitiligo is the most common pigmentary disorder and is considered a chronic, cumulative, multifactorial disease. The crucial role of cytotoxic CD8+ T lymphocytes and the IFNγ/CXCL10 axis has been demonstrated in its pathogenesis. Objective To evaluate the clinical profile and immuno-inflammatory markers in patients with vitiligo in a reference medical center. Methods Cross-sectional study in which all patients with vitiligo seen at the medical center the from 2019 to 2022 were evaluated, to outline the clinical profile. Moreover, cardiovascular risk biomarkers (neutrophil/lymphocyte ratio and C-reactive protein levels) were measured, as well as cytokines and chemokines (TNFα, IFNγ, IL10, IL15 and CXCL10) in the serum of a subgroup of 30 patients. Results There was a predominance of females, with a mean age of 43 years. Most were phototypes IV or V (71.3%), without comorbidities (77.55%), and without a family history of vitiligo (70.41%). Higher levels of neutrophil/lymphocyte ratio, C-reactive protein, and inflammatory cytokines/chemokines were documented in vitiligo patients when compared to the control group (non-significant). As relevant data, the highest values of CXCL10 were detected in patients with vitiligo versus controls, as well as in patients with disease of shorter duration (p < 0.05). Study limitations The number of assessed patients was small due to recruitment difficulties caused by the COVID-19 pandemic. Conclusion The present data contribute to confirming the relevant role of the IFNγ/CXCL10 axis in the pathogenesis of vitiligo, highlighting CXCL10 as a possible activity marker.

The leprosy reaction is associated with salivary anti-Porphyromonas gingivalis IgA antibodies.

The aim of the study was to evaluate the association between salivary anti-Porphyromonas gingivalis IgA antibodies and the leprosy reaction. The levels of salivary anti - P. gingivalis IgA antibodies, together with salivary flow and pH were measured in individuals diagnosed with leprosy and associated with the development of the leprosy reaction. Saliva was collected from 202 individuals diagnosed with leprosy at a reference leprosy treatment center, 106 cases with the leprosy reaction and 96 controls without the leprosy reaction. Anti - P. gingivalis IgA was evaluated by indirect immunoenzyme assay. Non-conditional logistic regression analysis was employed to estimate the association between antibody levels and the leprosy reaction. There was a positive statistically significant association between the levels of anti - P. gingivalis IgA and the presence of the leprosy reaction, controlling for confounders: age, sex, level of education and alcoholic beverage consumption: ORajusted: 2.55; IC 95%: 1.34-4.87. Individuals with leprosy who had high levels of salivary anti - P. gingivalis IgA had approximately twice as many chances of developing the leprosy reaction. The findings suggest a possible relationship between salivary anti - P. gingivalis IgA antibodies and the leprosy reaction.

Exuberant case of verrucous cutaneous leishmaniasis

Abstract Cutaneous leishmaniasis represents a public health problem that affects 85 countries. It is an endemic disease in Brazil, having an important socioeconomic impact. An exuberant case of cutaneous leishmaniasis is reported herein. A 28-year-old male patient with Down syndrome had had verrucous plaques on the back for over a year, with progressive growth. PCR of a lesion sample was positive for Leishmania braziliensis. The patient's condition was classified as atypical cutaneous leishmaniasis. He was successfully treated with amphotericin B and miltefosine. The treatment remains a challenge, given the toxicity and low cure rate of the currently recommended drugs.

Effect of immunonutrition on serum levels of C-reactive protein and lymphocytes in patients with COVID-19: a randomized, controlled, double-blind clinical trial.

INTRODUCTION: Introduction: patients with COVID-19 undergo changes in leukocyte count, respiratory disorders, and an increase in inflammatory substances. To improve the inflammatory condition, some nutrients can be used, including arginine, omega-3 fatty acids and nucleotides. This study aims to evaluate how oral immunonutrient supplements affects serum C-reactive protein (CRP) levels and lymphocyte count in patients with COVID-19. Methods: in this double-blind clinical trial, we randomized 43 adult patients with COVID-19 to receive a standard high-protein normocaloric supplement (control) or an immunonutrient-enriched supplement (experiment) for 7 days. The primary outcome was to evaluate changes in total lymphocyte count and serum level of CRP. The assessment of risk and nutritional status of these patients was also performed. Results: forty-three patients with mean age of 41.5 (± 1.8) years were followed up, 39.5 % of them women. The mean body mass index was 27.6 (± 0.8) kg/m² and 58.1 % had low nutritional risk. In the experiment group, there was a CRP reduction of 23.6 (± 7.5) mg/L, while in the control branch the decrease was 14.8 (± 12.1) mg/L (p = 0.002). There was an increase in lymphocytes in the experiment group (+367.5 ± 401.8 cells/mm³) and a reduction in the control group (-282.8 ± 327.8 cells/mm³), although there was no statistical significance (p = 0.369). Relative risk (RR) of treatment in reducing CRP by 30 % or more was 4.45 (p < 0.001; 95 % CI, 1.79-11.07). RR in increasing lymphocyte count by 30 % or more was 1.28 (p = 0.327; 95 % CI, 0.67-2.45). Conclusion: we conclude that immunonutrient supplements seem to reduce CRP levels more than standard high-protein normocaloric supplements.

INTRODUCCIÓN: Introducción: los pacientes con COVID-19 sufren cambios en el recuento de leucocitos, trastornos respiratorios y aumento de sustancias inflamatorias. Para mejorar la condición inflamatoria se pueden usar algunos nutrientes, como la arginina, los ácidos grasos omega-3 y los nucleótidos. Este estudio tiene como objetivo evaluar cómo los suplementos de inmunonutrientes orales afectan a los niveles séricos de proteína C-reactiva (PCR) y al recuento de linfocitos en pacientes con COVID-19. Métodos: en este ensayo clínico doble ciego, aleatorizamos a 43 pacientes adultos con COVID-19 para recibir un suplemento normocalórico estándar alto en proteínas (control) o un suplemento enriquecido con inmunonutrientes (experimento) durante 7 días. El resultado primario fue evaluar los cambios en el recuento total de linfocitos y el nivel sérico de PCR. También se realizó la evaluación del riesgo y el estado nutricional de estos pacientes. Resultados: cuarenta y tres pacientes con edad media de 41,5 (± 1,8) años fueron seguidos, el 39,5 % de ellos mujeres. El índice de masa corporal medio fue de 27,6 (± 0,8) kg/m² y el 58,1 % tenían bajo riesgo nutricional. En el grupo experimental hubo una reducción de la PCR de 23,6 (± 7,5) mg/L, mientras que en la rama de control la disminución fue de 14,8 (± 12,1) mg/L (p = 0,002). Hubo un aumento de linfocitos en el grupo experimental (+367,5 ± 401,8 células/mm³) y una reducción en el grupo de control (-282,8 ± 327,8 células/mm³), aunque no hubo significación estadística (p = 0,369). El riesgo relativo (RR) del tratamiento para reducir la PCR en un 30 % o más fue de 4,45 (p < 0,001; IC 95 %: 1,79-11,07). El RR en el aumento del recuento de linfocitos en un 30 % o más fue de 1,28 (p = 0,327; IC 95 %: 0,67-2,45). Conclusión: se concluye que los suplementos de inmunonutrientes parecen reducir los niveles de PCR más que los suplementos normocalóricos estándar altos en proteína.

Exuberant case of verrucous cutaneous leishmaniasis.

Cutaneous leishmaniasis represents a public health problem that affects 85 countries. It is an endemic disease in Brazil, having an important socioeconomic impact. An exuberant case of cutaneous leishmaniasis is reported herein. A 28-year-old male patient with Down syndrome had had verrucous plaques on the back for over a year, with progressive growth. PCR of a lesion sample was positive for Leishmania braziliensis. The patient's condition was classified as atypical cutaneous leishmaniasis. He was successfully treated with amphotericin B and miltefosine. The treatment remains a challenge, given the toxicity and low cure rate of the currently recommended drugs.

Immunoassay standardization for the detection of immunoglobulin A (IgA) against Porphyromonas gingivalis antigens in saliva of individuals with and without leprosy.

Leprosy reactions are immune processes that cause neural damage in individuals with leprosy. As periodontitis is an infectious disease related to its development, specific antibodies to periodontal pathogens must be evaluated to better understand the humoral mechanisms underlying this relationship. Therefore, the objective of this study was to standardize an immunoassay to measure IgA specific to P. gingivalis antigens in the saliva of individuals with leprosy. An ELISA checkerboard titration was performed. A validation test involving 53 individuals with leprosy, 24 with and 19 without periodontitis, was conducted and a ROC curve constructed to calculate sensitivity and specificity. The coefficient of the optical densities was 2.21 and 2.66 for P. gingivalis crude extract and the recombinant protein HmuY, respectively. Sensitivity and specificity for the P. gingivalis crude extract were 66.7% and 73.7%, respectively, and for HmuY, were 62.5% and 52.6%, respectively. Specific recognition of P. gingivalis occurred predominantly in individuals with periodontitis, which validates the use of this test for studying periodontitis in individuals with leprosy.Trial registration CAEE 64476117.3.0000.0049, 21/07/2017, retrospectively registered.

Plantar ulcer as an atypical manifestation of cutaneous leishmaniasis

Abstract Cutaneous leishmaniasis is characterized by ulcers with raised edges and a granular bottom, mainly on the lower limbs. This is a case report of a male patient with an ulcer on the left plantar region. The diagnosis was confirmed by positive PCR for L. braziliensis and the presence of amastigotes of Leishmania sp. in the histopathological examination. After treatment with Glucantime, the patient showed full healing of the ulcer. The unusual location of the ulceration calls attention to atypical presentations of leishmaniasis, and the importance of histopathological examination and PCR, leading to the appropriate diagnosis and treatment.

Plantar ulcer as an atypical manifestation of cutaneous leishmaniasis.

Cutaneous leishmaniasis is characterized by ulcers with raised edges and a granular bottom, mainly on the lower limbs. This is a case report of a male patient with an ulcer on the left plantar region. The diagnosis was confirmed by positive PCR for L. braziliensis and the presence of amastigotes of Leishmania sp. in the histopathological examination. After treatment with Glucantime, the patient showed full healing of the ulcer. The unusual location of the ulceration calls attention to atypical presentations of leishmaniasis, and the importance of histopathological examination and PCR, leading to the appropriate diagnosis and treatment.

Human CD8+ T Cells Release Extracellular Traps Co-Localized With Cytotoxic Vesicles That Are Associated With Lesion Progression and Severity in Human Leishmaniasis.

Cell death plays a fundamental role in mounting protective and pathogenic immunity. Etosis is a cell death mechanism defined by the release of extracellular traps (ETs), which can foster inflammation and exert microbicidal activity. While etosis is often associated with innate cells, recent studies showed that B cells and CD4+ T cells can release ETs. Here we investigate whether CD8+ T cells can also release ETs, which might be related to cytotoxicity and tissue pathology. To these ends, we first employed an in vitro system stimulating human CD8+ T cells isolated from healthy volunteers with anti-CD3/anti-CD28. Using time-frame video, confocal and electron microscopy, we demonstrate that human CD8+ T cells release ETs upon stimulation (herein LETs - lymphocyte extracellular traps), which display unique morphology and functional characteristics. CD8+ T cell-derived LETs form long strands that co-localize with CD107a, a marker of vesicles containing cytotoxic granules. In addition, these structures connect the LET-releasing cell to other neighboring cells, often resulting in cell death. After demonstrating the release of LETs by human CD8+ T cells in vitro, we went on to study the occurrence of CD8-derived LETs in a human disease setting. Thus, we evaluated the occurrence of CD8-derived LETs in lesions from patients with human tegumentary leishmaniasis, where CD8+ T cells play a key role in mediating pathology. In addition, we evaluated the association of these structures with the intensity of the inflammatory infiltrate in early and late cutaneous, as well as in mucosal leishmaniasis lesions. We demonstrated that progression and severity of debilitating and mutilating forms of human tegumentary leishmaniasis are associated with the frequency of CD8+ T cells in etosis, as well as the occurrence of CD8-derived LETs carrying CD107a+ vesicles in the lesions. We propose that CD8+ T cell derived LETs may serve as a tool for delivering cytotoxic vesicles to distant target cells, providing insights into mechanisms of CD8+ T cell mediated pathology.

Tissue Damage in Human Cutaneous Leishmaniasis: Correlations Between Inflammatory Cells and Molecule Expression.

Cutaneous leishmaniasis (CL) is caused by the bite of the infected sand fly, which inoculates parasites of Leishmania spp and triggers an immune response. An exacerbated cutaneous inflammatory response is crucial for controlling parasite burden but can also promote tissue damage. This study aimed to characterize the populations of natural killer (NK), CD57+, CD4+, and CD8+ T cells, CD20+ B cells, as well as CD68+ macrophages, in biopsies of ulcerated CL lesions, and quantify the production of perforin+, grazyme B+, interleukin 1 beta (IL-1ß+) and Tumor Necrosis Factor (TNF-α+ cells). We then correlated these parameters with necrosis, inflammation and the number of amastigotes. CD4+ T cells were positively correlated to the extent of inflammation, B cells and IL-1ß+ were associated with the extent of necrosis, CD68+ macrophages and perforin were correlated with the number of amastigotes, and CD57+ NK cells was correlated to CD68+ macrophages and amastigotes. In sum, the finding suggests that the production of cytotoxic granules and cytokines by inflammatory cells contributes to tissue damage in CL lesions.

Phonotherapeutic Intervention in Patients With Mucosal Leishmaniasis Sequelae.

PURPOSE: To characterize the voice before and after speech-language intervention, with Humming nasal sound in patients with sequelae Mucosal Leishmaniasis (ML) and Cutaneous Leishmaniasis (CL). METHODS: Collection of phonation /a:/ from 44 patients with ML and CL for perceptual voice analysis and computed acoustic. The Wilcoxon nonparametric test and Fisher's exact test were used, with significance level of 5%. RESULTS: It was observed, prespeech therapy, that 27.7% of participants with ML presented asthenic vocal quality, and for the acoustics characteristics there was a statistically significant result for measures of frequency, frequency disturbance, noise, and subharmonic measurements, indicating phonatory instability, weakness, and noise emission giving the emission a feeling of vocal weakness. After therapy, the subharmonic segment measurements for the group with ML, showing reduction noise emission. Patients with CL had more grade 1 instability (36.4%), indicating tremor in vocal tract structures. After speech therapy, this group presented a reduction in the degree of roughness and reduction of the frequency disturbance measures, indicating a decrease in tension in the larynx and pharynx. CONCLUSION: Even after completing treatment for LM, patients may experience vocal changes due to the sequelae of the disease, like vocal alterations due to nasal lesions or in other locations that interfere in the correct vocal emission. As for participants with CL, no vocal changes would be expected, since these patients present thorax, leg and arm lesions that would not cause problems for the voice. Nevertheless, the two groups of participants presented vocal changes to different degrees before vocal therapy. However, it was observed that patients with ML present vocal alterations with more severe degrees. After the speech-language intervention, the participants of both groups showed vocal improvement, but the group with CL presented more vocal benefits, possibly due to the previous vocal alterations not being so severe.

In Situ Cellular Response Underlying Successful Treatment of Mucosal Leishmaniasis with a Combination of Pentavalent Antimonial and Pentoxifylline.

Mucosal leishmaniasis (ML) is characterized by high production of inflammatory cytokines. Administration of pentoxifylline (PTX), an inhibitor of TNF-alpha, with pentavalent antimony (Sbv), has been successfully used as alternative treatment for refractory ML. Our study aims to investigate the in situ cellular response underlying the effectiveness of this therapy, by evaluating the intensity of the inflammatory infiltrate, cellular composition, and expression of cytokines and granzyme A in lesions from ML before and after treatment with Sbv alone or in combination with PTX. Our data showed no differences in the intensity of inflammatory infiltrate comparing before and after treatment, and comparing between different treatments. However, although the number and frequency of CD4+ and CD8+ cells were not different before and after treatments or comparing different treatments, frequency of CD68+ cells decreased after treatment with Sbv + PTX, but not with Sbv. This was due to a reduction in CD68+ TNF-alpha+ and not in CD68+ IL-10+ cells. The frequency of TNF-alpha+ cells was correlated with the intensity of the inflammatory infiltrate before treatment, but this correlation was lost after treatment with Sbv + PTX. Although the total expression of granzyme A did not significantly change after treatments, a clear trend of decrease was observed after treatment with Sbv + PTX. Interestingly, patients who took longer to heal, regardless of the treatment, displayed a higher frequency of granzyme A+ cells. Our data suggest that treatment with Sbv + PTX acts in CD68+ cells reducing the expression of TNF-alpha but not IL-10, resulting in more efficient modulation of the inflammatory response, accelerating the healing process.

Disseminated leishmaniasis: clinical, pathogenic, and therapeutic aspects.

Disseminated leishmaniasis is a severe and emerging form of American tegumentary leishmaniasis. Disseminated leishmaniasis is defined by the presence of more than 10 polymorphic cutaneous lesions, distributed over more than two noncontiguous parts of the body. Nasal mucosal involvement is observed in almost half of cases. Disseminated leishmaniasis patients present with a decreased production of Th1 cytokines in the peripheral blood due to the attraction of leishmania- activated T cells to the multiple cutaneous lesions. Disseminated leishmaniasis development is poorly understood and is related to a complex network involving environmental, host immune response, and parasite factors, in which L. braziliensis polymorphism plays an important role. Disseminated leishmaniasis is a challenging disease to cure, presenting a high failure rate of 75% to pentavalent antimony therapy. Despite its importance and severity, this form of American tegumentary leishmaniasis has been poorly studied and documented, deserving greater attention from professionals working in endemic areas.

Disseminated leishmaniasis: clinical, pathogenic, and therapeutic aspects

Abstract: Disseminated leishmaniasis is a severe and emerging form of American tegumentary leishmaniasis. Disseminated leishmaniasis is defined by the presence of more than 10 polymorphic cutaneous lesions, distributed over more than two noncontiguous parts of the body. Nasal mucosal involvement is observed in almost half of cases. Disseminated leishmaniasis patients present with a decreased production of Th1 cytokines in the peripheral blood due to the attraction of leishmania- activated T cells to the multiple cutaneous lesions. Disseminated leishmaniasis development is poorly understood and is related to a complex network involving environmental, host immune response, and parasite factors, in which L. braziliensis polymorphism plays an important role. Disseminated leishmaniasis is a challenging disease to cure, presenting a high failure rate of 75% to pentavalent antimony therapy. Despite its importance and severity, this form of American tegumentary leishmaniasis has been poorly studied and documented, deserving greater attention from professionals working in endemic areas.

Whole blood profiling of leprosy type 1(reversal) reactions highlights prominence of innate immune response genes.

BACKGROUND: The major factors contributing for nerve damage and permanent disabilities in leprosy are type 1 or reversal reactions (RR) and type 2 or erythema nodosum leprosum (ENL). Gene profiling of leprosy reactions have shown that different pathways are activated during the course of reactions, which is consistent with the exacerbated immune response exhibited by these patients. METHODS: We used qPCR to screen a panel of 90 genes related to the immune response in leprosy in RNA-derived peripheral leukocytes of patients with (N = 94) and without leprosy reactions (N = 57) in order to define expression signatures correlated to RR or ENL. RESULTS: Our results show that there is a marked signature for RR in the blood, comprising genes mostly related to the innate immune responses, including type I IFN components, autophagy, parkins and Toll like receptors. On the other hand, only Parkin was differentially expressed in the ENL group. CONCLUSIONS: The data put together corroborates previous work that brings evidence that an acute uncontrolled exacerbated immune response designed to contain the spread of M. leprae antigens might be cause of RR pathogenesis. Identifying a blood profile useful to predict leprosy reactions prior to its development might help to reduce the morbidity associated to this disabling disease.

Safety and efficacy of miltefosine monotherapy and pentoxifylline associated with pentavalent antimony in treating mucosal leishmaniasis.

INTRODUCTION: Mucosal Leishmaniasis (ML) is a difficult to treat and severe form of Leishmaniasis. In general, more than 40% of subjects with ML have therapeutic failure upon the use of pentavalent antimony (Sbv) at 20mg/kg/day during 30 days. Additionally, Sbv is a toxic drug that requires parenteral administration, and many patients will need several courses to be cured. In cases that cannot be treated or cured by Sbv, the alternative is amphotericin B, another toxic and parenteral drug. As a consequence, many ML patients will be cured only after years of disease and may present several morbidities due to the aggressiveness of the disease or toxicity related to the treatment. Areas covered: We aimed to review clinical trials with Miltefosine or Sbv associated with pentoxifylline in the treatment of ML. Expert commentary: There are few studies to define more effective and safer therapy in mucosal disease caused by Leishmania, with an urgent need to supporting and funding well designed trials. Miltefosine monotherapy, as well as pentoxifylline combined with Sbv are promising therapeutic approaches to increase the cure rate of this neglected disease.

Dynamics of American tegumentary leishmaniasis in a highly endemic region for Leishmania (Viannia) braziliensis infection in northeast Brazil.

BACKGROUND: American Tegumentary Leishmaniasis (ATL) caused by Leishmania braziliensis is endemic in Corte de Pedra, Northeast Brazil. Most L. braziliensis infections manifest as localized cutaneous leishmaniasis (CL). Disseminated manifestations include mucosal leishmaniasis (ML), present at a low constant level for several decades, and newly emerging disseminated leishmaniasis (DL). Surprisingly, DL has recently surpassed ML in its spatial distribution. This led us to hypothesize that distinct forms of ATL might spread in different patterns through affected regions. METHODOLOGY/PRINCIPAL FINDINGS: We explored the incidence and geographic dispersion of the three clinical types of ATL over a span of nearly two decades in Corte de Pedra. We obtained the geographic coordinates of the homes of patients with ATL during 1992-1996, 1999-2003 and 2008-2011. The progressive dispersion of ML or DL in each time period was compared to that of CL in 2008-2011 with the Cusick and Edward's geostatistical test. To evaluate whether ATL occurred as clusters, we compared each new case in 2008-2011 with the frequency of and distance from cases in the previous 3 to 12 months. The study revealed that DL, ML and CL actively spread within that region, but in distinct patterns. Whereas CL and DL propagated in clusters, ML occurred as sporadic cases. DL had a wider distribution than ML until 2003, but by 2011 both forms were distributed equally in Corte de Pedra. The incidence of ML fluctuated over time at a rate that was distinct from those of CL and DL. CONCLUSIONS/SIGNIFICANCE: These findings suggest that CL and DL maintain endemic levels through successive outbreaks of cases. The sporadic pattern of ML cases may reflect the long and variable latency before infected patients develop clinically detectable mucosal involvement. Intimate knowledge of the geographic distribution of leishmaniasis and how it propagates within foci of active transmission may guide approaches to disease control.