ABSTRACT
BACKGROUND: Sporotrichosis is a subcutaneous mycosis caused by dimorphic pathogenic fungi belonging to the Sporothrix genus. Pathogenic Sporothrix species typically produce melanin, which is known to be a virulence factor. OBJECTIVES: The aim of this study was to perform phenotypic, genotypic, and virulence analyses of two distinct Sporothrix brasiliensis strains isolated from the same lesion on a patient from Rio de Janeiro. METHODS AND FINDINGS: Genotypic analyses by partial sequencing of the calmodulin, ß-tubulin, and chitin synthase genes, as well as polymerase chain reaction (PCR)-fingerprinting by T3B, M13, and GACA, showed that the isolates were very similar but not identical. Both isolates had similar phenotypic characteristics and effectively produced melanin in their yeast forms, accounting for their ability of causing disease in a murine sporotrichosis model. Remarkably, isolate B was albino in its environmental form but caused more severe disease than the pigmented A isolate. CONCLUSIONS: These findings indicate that the patient was infected by two genetically and biologically distinct S. brasiliensis that vary in their production of melanin in their environmental forms. The results underscore the importance of characterizing phenotypically different isolates found in the same clinical specimen or patient.
Subject(s)
Antifungal Agents/pharmacology , Sporothrix/pathogenicity , Sporotrichosis/pathology , Sporotrichosis/virology , Animals , DNA Fingerprinting , Disease Models, Animal , Genotype , Humans , Mice , Mice, Inbred BALB C , Microbial Sensitivity Tests , Phenotype , Polymerase Chain Reaction , Sporothrix/drug effects , Sporothrix/genetics , VirulenceABSTRACT
BACKGROUND: Cutaneous leishmaniasis (CL) generally presents with a single or several localised cutaneous ulcers without involvement of mucous membranes. Ulcerated lesions are susceptible to secondary contamination that may slow the healing process. OBJECTIVE: This study verified the influence of non-parasitic wound infection on wound closure (epithelialisation) and total healing. METHODS: Twenty-five patients with a confirmed diagnosis of CL and ulcerated lesions underwent biopsy of ulcer borders. One direct microbial parameter (germ identification in cultures) and four indirect clinical parameters (secretion, pain, burning sensation, pruritus) were analysed. FINDINGS Biopsies of ten lesions showed secondary infection by one or two microorganisms (Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecalis, Streptococcus pyogenes and Candida parapsilosis). "Secretion" and "burning sensation" influenced epithelialisation time but not total healing time. Positive detection of germs in the ulcer border and "pain" and "pruritus" revealed no influence on wound closure. CONCLUSIONS: Our borderline proof of clinical CL ulcer infection inhibiting CL wound healing supports the need to follow antimicrobial stewardship in CL ulcer management, which was recently proposed for all chronic wounds.
Subject(s)
Coinfection/microbiology , Leishmaniasis, Cutaneous/microbiology , Wound Healing , Adolescent , Adult , Aged , Child , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prospective Studies , Young AdultABSTRACT
BACKGROUND: American tegumentary leishmaniasis (ATL) is a non-lethal parasitic disease that presents with cutaneous (CL) and mucosal (ML) clinical forms. ATL treatment aims at healing the lesions and preventing the development of the late mucosal form. Systemic meglumine antimoniate (MA) therapy with 10-20 mg Sb5+/kg/day is the first choice of treatment. However, alternative therapies using 5 mg Sb5+/kg/day or intralesional (IL) MA are the usual regimens at the National Institute of Infectious Diseases (NIID), Rio de Janeiro, Brazil. OBJECTIVES: To evaluate lethality and the incidence of relapse and development of late ML in CL patients treated at NIID from 2001 until 2013. METHODS: Data were recovered from records of all ATL patients diagnosed during that period. FINDINGS: Out of 777 patients, 753 were treated with MA (96.9%). Of those, 89.1% received alternative therapy of 9.9% IL and 79.2% systemic 5 mg Sb5+/kg/day. Some patients required 1-3 additional courses of treatment, thus making a total of 997 courses; 85.2% of them were subjected to alternative therapies. Lethality was 0.1%, relapse incidence 5.8%, and late ML incidence 0.25%. As a final outcome for the 777 patients, 95.9% were cured, 0.1% died and 4.0% were not able to follow-up. MAIN CONCLUSIONS: Alternative MA schedules resulted in low lethality without increase of relapse or late ML incidence.
Subject(s)
Antiprotozoal Agents/administration & dosage , Leishmaniasis, Cutaneous/drug therapy , Meglumine/administration & dosage , Organometallic Compounds/administration & dosage , Adult , Cohort Studies , Female , Humans , Incidence , Injections, Intralesional , Leishmaniasis, Cutaneous/mortality , Male , Meglumine Antimoniate , Middle Aged , Recurrence , Retrospective Studies , Treatment OutcomeABSTRACT
INTRODUCTION: American Tegumentary Leishmaniasis (ATL) treatment is based on pentavalent antimonials (Sb5+), but these drugs have been associated to several adverse effects. Hearing loss and tinnitus during treatment with meglumine antimoniate (MA) have already been reported. This study aimed to describe the usefulness of self-reporting of hearing loss and tinnitus in diagnosing MA-induced ototoxicity. METHODS: A prospective longitudinal study was conducted with 102 patients with parasitological diagnosis of ATL, treated with different MA schemes. The presence of clinical auditory toxicity was defined as the emergence or worsening of self-reporting hearing loss and/or tinnitus during monitoring. Measures of sensitivity, specificity, and the positive and negative predictive value of the patient's self-reporting of hearing loss and tinnitus in relation to the result of the audiometric test (considered the gold standard) were calculated. RESULTS: The age of the evaluated patients ranged from 15 to 81 years, with a median of 41 years, and most were male (73.5%). Seventy-five patients (73.5%) had cutaneous leishmaniasis and 27 (26.5%) mucosal leishmaniasis. Eighty-six patients (84.3%) received intramuscular (IM) treatment and 16 (15.7%) were treated with intralesional MA. During treatment, 18 (17,6%) had tinnitus and 7 (6,9%) had complaint of hearing loss. 53 (52%) patients had cochlear toxicity confirmed by tone threshold audiometry and high frequency audiometry, from which 60% received a dose of 20 mg Sb5+/kg/day (p = 0.015) and 96.2% were treated with IM MA (p = 0.001). Tinnitus has greater specificity and positive predictive value than hearing loss, with a low number of false positives, but with a high false negative value. CONCLUSION: Although the large number of false negatives suggests that self-report of hearing loss or tinnitus cannot be considered a good screening test for referring the patient to an audiometry, the low number of false positives suggests the need to value the patient's complaint for referral. Otherwise, this study reinforces the importance of audiological monitoring during treatment with MA, especially in those patients with self-reporting of hearing loss or tinnitus when treated with 20 mg Sb5+/kg/day via IM.
Subject(s)
Antiprotozoal Agents , Deafness , Hearing Loss , Leishmaniasis, Cutaneous , Organometallic Compounds , Ototoxicity , Tinnitus , Humans , Male , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Female , Meglumine Antimoniate/adverse effects , Tinnitus/chemically induced , Tinnitus/diagnosis , Tinnitus/drug therapy , Meglumine/adverse effects , Antiprotozoal Agents/therapeutic use , Longitudinal Studies , Prospective Studies , Organometallic Compounds/adverse effects , Leishmaniasis, Cutaneous/diagnosis , Leishmaniasis, Cutaneous/drug therapy , Hearing Loss/chemically induced , Hearing Loss/diagnosisABSTRACT
BACKGROUND: Sporotrichosis is a subcutaneous or implantation mycosis caused by some species of the genus Sporothrix. Rio de Janeiro state, Brazil, experiences hyperendemic levels of zoonotic sporotrichosis, with increasing cases of disseminated disease, especially in people living with HIV (PLHIV). Involvement of the nasal mucosa is rare and occurs isolated or in disseminated cases, with a delayed resolution. METHODOLOGY/PRINCIPAL FINDINGS: This study aimed to describe the epidemiological, clinical, and therapeutic profiles of 37 cases of sporotrichosis with involvement of the nasal mucosa treated at the ear, nose, and throat (ENT) outpatient clinic of the Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, from 1998 to 2020. Data were reviewed from the medical records and stored in a database. The Mann-Whitney test was used to compare the means of quantitative variables, and Pearson chi-square and Fisher's exact tests were used to verify the association between qualitative variables (p<0.05). Most patients were males, students or retirees, with a median age of 38 years, residents in the municipality of Rio de Janeiro, and infected through zoonotic transmission. Disseminated sporotrichosis forms in patients with comorbidities (mostly PLHIV) were more common than the isolated involvement of the mucosa. The main characteristics of lesions in the nasal mucosa were the presence/elimination of crusts, involvement of various structures, mixed appearance, and severe intensity. Due to therapeutic difficulty, itraconazole was combined with amphotericin B and/or terbinafine in most cases. Of the 37 patients, 24 (64.9%) healed, with a median of 61 weeks of treatment, 9 lost follow-up, 2 were still treating and 2 died. CONCLUSIONS: Immunosuppression was determinant to the outcome, with worse prognosis and lower probability of cure. Notably in this group, the systematization of the ENT examination for early identification of lesions is recommended to optimize the treatment and outcome of the disease.
Subject(s)
Sporothrix , Sporotrichosis , Male , Humans , Adult , Female , Sporotrichosis/drug therapy , Sporotrichosis/epidemiology , Sporotrichosis/diagnosis , Retrospective Studies , Brazil/epidemiology , Itraconazole/therapeutic use , Nasal Mucosa , Antifungal Agents/therapeutic useABSTRACT
New world cutaneous leishmaniasis (NWCL) is an anthropozoonosis caused by different species of the protozoan Leishmania. Colorimetric in situ hybridization (CISH) was shown to satisfactorily detect amastigote forms of Leishmania spp. in animal tissues, yet it was not tested for the diagnosis of human NWCL. The aim of this study was to compare CISH, histopathology (HP), and immunohistochemistry (IHC) techniques to diagnose NWCL in human cutaneous lesions. The sample comprised fifty formalin-fixed, paraffin-embedded skin biopsy specimens from patients with NWCL caused by L. (V.) braziliensis. These specimens were analyzed by CISH, using a generic probe for Leishmania, IHC, and HP to assess the sensitivity of these methods by using a parasitological culture as a standard reference. Additional specimens from three patients diagnosed with cutaneous mycoses were also included to evaluate cross-reactions between CISH and IHC. The sensitivities of IHC, CISH, and HP for detecting amastigotes was 66%, 54%, and 50%, respectively. IHC, unlike CISH, cross-reacted with different species of fungi. Together, these results demonstrate that CISH may be a complementary assay for the detection of amastigote in the laboratorial diagnosis routine of human NWCL caused by L. (V.) braziliensis.
ABSTRACT
BACKGROUND: Sporotrichosis is the most common subcutaneous mycosis in Rio de Janeiro. Histopathological examination reveals diffuse granulomatous and suppurative dermatitis, and the fungus is rarely identifiable in tissue. We describe the histopathological features of cutaneous sporotrichosis, and investigate the association between them and the lack of visualization of the fungus. METHODS: A total of 119 samples of confirmed sporotrichosis cases were studied. The characteristics of the inflammatory infiltrate, the presence of epidermal changes, necrosis and fibrosis, and the parasite burden were analyzed. The association between histopathological changes and the lack of visualization of the fungus was evaluated using prevalence ratios. RESULTS: Granulomas were observed in all samples, suppurative granulomas in 100 (84%) and diffuse dermatitis in 114 (95.8%). Liquefaction and caseous necrosis were present in 78 (65.5%) and 52 (43.7%) samples, respectively. The fungus was not seen in 77 (64.7%) samples. Epithelioid, tuberculoid or foreign-body-type granulomas, caseous, fibrinoid or absent necrosis, predominance of lymphocytes among nonphagocytic cells and fibrosis were associated with the lack of visualization of the fungus. CONCLUSION: The histopathological characteristics of sporotrichosis were variable when the causative fungus was not seen. In a proper context, the diagnosis of sporotrichosis remains a potential consideration even in the absence of demonstrable yeast.
Subject(s)
Sporotrichosis/microbiology , Sporotrichosis/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Brazil , Child , Female , Granuloma/microbiology , Humans , Male , Middle Aged , Necrosis , Skin/microbiology , Skin/pathology , Young AdultABSTRACT
Glucantime (SbV) is the first-line treatment against American Tegumentary Leishmaniasis. Resistance cases to this drug have been reported and related to host characteristics and parasite phenotypes. In this study, 12 Leishmania (Viannia) braziliensis isolates from patients that presented clinical cure (Responders-R) and relapse or therapeutic failure (Non-responders-NR) after treatment with antimony, were analyzed. These parasites were assessed by in vitro susceptibility to SbIII and SbV, serine proteases activity measured with substrate (z-FR-AMC) and specific inhibitors (TLCK, AEBSF and PMSF). In vitro susceptibility of axenic amastigotes to SbIII showed a significant difference between R and NR groups. The protease assays showed that TLCK inhibited almost 100% of activity in both axenic amastigotes and promastigotes while AEBSF inhibited around 70%, and PMSF showed lower inhibition of some isolates. Principal component and clustering analysis performed with these data yielded one homogeneous cluster with only NR isolates and three heterogeneous clusters with R and NR isolates. Additionally, differential expression of subtilisins (LbrM.13.0860 and LbrM.28.2570) and TXNPx (LbrM.15.1080) was evaluated in promastigotes and axenic amastigotes from both groups. The results showed a higher expression of LbrM.13.0860 and LbrM.15.1080 genes in axenic amastigotes, while LbrM.28.2570 gene had the lowest expression in all isolates, regardless of the parasite form. The data presented here show a phenotypic heterogeneity among the parasites, suggesting that exploration of in vitro phenotypes based on SbIII and serine proteases profiles can aid in the characterization of L. (V.) braziliensis clinical isolates.
Subject(s)
Antimony/pharmacology , Leishmania braziliensis/drug effects , Leishmania braziliensis/enzymology , Serine Proteases/metabolism , Host-Parasite Interactions/drug effects , Parasitology , Serine Proteases/geneticsABSTRACT
BACKGROUND: Treatment of cutaneous leishmaniasis (CL) remains challenging since the drugs currently used are quite toxic, thus contributing to lethality unrelated to the disease itself but to adverse events (AE). The main objective was to evaluate different treatment regimens with meglumine antimoniate (MA), in a reference center in Rio de Janeiro, Brazil. METHODOLOGY: A historical cohort of 592 patients that underwent physical and laboratory examination were enrolled between 2000 and 2017. The outcome measures of effectiveness were epithelialization and complete healing of cutaneous lesions. AE were graded using a standardized scale. Three groups were evaluated: Standard regimen (SR): intramuscular (IM) MA 10-20 mg Sb5+/kg/day during 20 days (n = 46); Alternative regimen (AR): IM MA 5 mg Sb5+/kg/day during 30 days (n = 456); Intralesional route (IL): MA infiltration in the lesion(s) through subcutaneous injections (n = 90). Statistical analysis was performed through Fisher exact and Pearson Chi-square tests, Kruskal-Wallis, Kaplan-Meier and log-rank tests. RESULTS: SR, AR and IL showed efficacy of 95.3%, 84.3% and 75.9%, with abandonment rate of 6.5%, 2.4% and 3.4%, respectively. IL patients had more comorbidities (58.9%; p = 0.001), were mostly over 50 years of age (55.6%), and had an evolution time longer than 2 months (65.6%; p = 0.02). Time for epithelialization and complete healing were similar in IL and IM MA groups (p = 0.9 and p = 0.5; respectively). Total AE and moderate to severe AE that frequently led to treatment interruption were more common in SR group, while AR and IL showed less toxicity. CONCLUSIONS/SIGNIFICANCE: AR and IL showed less toxicity and may be good options especially in CL cases with comorbidities, although SR treatment was more effective. IL treatment was an effective and safe strategy, and it may be used as first therapy option as well as a rescue scheme in patients initially treated with other drugs.
Subject(s)
Antiprotozoal Agents/administration & dosage , Leishmaniasis, Cutaneous/drug therapy , Meglumine Antimoniate/administration & dosage , Adolescent , Adult , Aged , Brazil , Female , Follow-Up Studies , Humans , Injections, Intralesional , Injections, Intramuscular , Leishmania/drug effects , Leishmania/physiology , Leishmaniasis, Cutaneous/parasitology , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
We compared the accuracy and reliability of three amplification systems for enzyme immunoassays in the detection of specific IgG antibodies for the diagnosis of cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis in patients from an endemic area in Rio de Janeiro, Brazil. Partially soluble antigens obtained from the promastigote forms of L. (V.) braziliensis were used. For development of the reaction, two chromogens, 1,2-orthophenylenediamine (OPD) and 3,3',5,5'-tetramethylbenzidine (TMB), and a fluorogen, 4-methylumbelliferylphosphate (MUP), were tested. The performance of each system was compared using the following parameters: accuracy, intraclass correlation coefficient (ICC), and area under the receiver operating characteristic (ROC) curve. Sensitivity was the same (97.4%) for all systems. The reliability was excellent (ICC = 98.6, 98.7, and 99.1%) and specificity was 93.7, 95.8, and 97.4% for OPD, MUP, and TMB, respectively, showing no statistical significance. Despite the absence of differences in the performance of the three systems, the use of TMB is suggested because of its operational advantages, such as low cost compared with fluorogens, easy manipulation, greater stability, and lower toxicity.
Subject(s)
Immunoenzyme Techniques/methods , Leishmaniasis, Cutaneous/diagnosis , Animals , Antigens, Protozoan/immunology , Benzidines/chemistry , Confidence Intervals , Humans , Hymecromone/analogs & derivatives , Hymecromone/chemistry , Immunoglobulin G/blood , Immunoglobulin G/immunology , Leishmania braziliensis/immunology , Phenylenediamines/chemistry , Predictive Value of Tests , ROC Curve , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
In Brazil, meglumine antimoniate is the first drug of choice for mucosal leishmaniasis treatment followed by amphotericin B and pentamidine isethionate. We report the case of a patient with severe mucosal lesions caused by Leishmania (Viannia) braziliensis that were difficult to treat. Over a 14-year period, the patient showed low adherence and three treatment attempts with meglumine antimoniate failed. Additionally, there was an unsatisfactory response to liposomal amphotericin B and nephrotoxicity when using amphotericin B deoxycholate that persisted after new treatment attempt with liposomal amphotericin B. Finally, healing was achieved with pentamidine isethionate and maintained during nine months of monitoring.
Subject(s)
Antiprotozoal Agents/therapeutic use , Leishmania braziliensis/drug effects , Leishmaniasis, Mucocutaneous/drug therapy , Pentamidine/therapeutic use , Humans , Male , Middle Aged , Treatment OutcomeABSTRACT
BACKGROUND: We identified the species of Leishmania isolated from traveling and migrant patients attended in a reference center from 2000 to 2015, we performed the georeferencing of these species in Rio de Janeiro (RJ) state and we had knowledge about the human flows between the likely location of infection (LLI) and place of residence (PR) in RJ state, Brazil. METHODOLOGY/PRINCIPAL FINDINGS: This is a retrospective cross-sectional study including 171 patients diagnosed with ATL. Google Maps, OpenStreetMap, and Bing Maps were tools used to georeference LLI and PR. For etiological identification, we used isoenzyme electrophoresis, polymerase chain reaction-restriction fragment length polymorphism (molecular target hsp70C with restriction enzymes HaeIII and BstUI), and sequencing of the internal transcribed spacer of ribosomal DNA. ARCGIS software was used to create maps of the geographic distribution of Leishmania species in the state and municipality of RJ, together with flows between the LLI and PR. Isolates from 104 patients were identified as: L. (Viannia) braziliensis (80.8%), L. (V.) naiffi (7.7%), L. (V.) guyanensis (6.7%), L. (Leishmania) amazonensis (1%), and genetic variants of L. (V.) braziliensis (3.8%). The flow maps showed that the LLI included 4 countries, 19 Brazilian states, and 18 municipalities of RJ state. The Brazilian states with the highest density of cases were Amazonas (n = 32), Bahia (n = 18), and Ceará (n = 15). CONCLUSIONS/SIGNIFICANCE: This work is the first contribution to the knowledge of the routes of Leishmania species introduced in RJ state by migrants and travelers patients. L. (V.) braziliensis, L. (V.) guyanensis, L. (V.) naiffi, L. (L.) amazonensis, and genetic variants of L. (V.) braziliensis were identified in RJ state. To determine whether the autochthonous transmission of these imported species is possible it is necessary the adaptation of these species to environmental conditions as well as the presence of reservoirs and phlebotomine vectors in this region.
Subject(s)
Leishmania/classification , Leishmania/isolation & purification , Leishmaniasis/epidemiology , Leishmaniasis/parasitology , Transients and Migrants , Adolescent , Adult , Aged , Aged, 80 and over , Brazil/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , DNA, Protozoan/genetics , DNA, Ribosomal/genetics , Female , Humans , Leishmania/genetics , Leishmaniasis/diagnosis , Male , Middle Aged , Phylogeny , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: Sporotrichosis in childhood is rare in most countries. Isolated cases and small outbreaks related to recreational activities or without identification of the transmission mechanism have been reported. METHODS: Series of case reports. The isolation of Sporothrix schenckii from exudates or fragments of lesions obtained from the patients was used as the criterion of inclusion in the study. RESULTS: A total of 81 cases of sporotrichosis in children younger than 15 years of age were diagnosed at the Evandro Chagas Research Institute, Fiocruz, Brazil, between 1998 and 2004. These cases are part of the endemic disease occurring in Rio de Janeiro related to contact with domestic cats. There was a predominance of girls in the 10-14 year age group. The most frequent clinical form was the cutaneouslymphatic form located on the upper limbs. Itraconazole was used as the first-choice treatment. Sixty-six patients were cured, 9 were lost to follow-up, and 6 had spontaneous regression of the lesions. CONCLUSIONS: This is the largest series of childhood sporotrichosis with zoonotic transmission. The clinical presentation of sporotrichosis in children followed the same pattern of the disease in adults in this ongoing endemic.
Subject(s)
Endemic Diseases , Sporothrix/isolation & purification , Sporotrichosis/epidemiology , Zoonoses/epidemiology , Zoonoses/microbiology , Adolescent , Animals , Antifungal Agents/therapeutic use , Brazil/epidemiology , Cats , Child , Child, Preschool , Conjunctiva/pathology , Dacryocystitis/microbiology , Dacryocystitis/pathology , Extremities/pathology , Female , Humans , Itraconazole/therapeutic use , Male , Sex Factors , Skin/pathology , Sporotrichosis/drug therapy , Sporotrichosis/physiopathology , Treatment OutcomeABSTRACT
Flow cytometry employing Leishmania (L.) chagasi (Lc) and L. (Viannia) braziliensis (Lb) antigen was used to establish the differential diagnosis between visceral (VL) and cutaneous leishmaniasis (CL) in dogs. Flow cytometry permitted the detection of Leishmania-specific immunoglobulin G in sera from 19 dogs: nine with CL and 10 with VL. A significant difference in the percentage of positive staining was observed in sera from dogs with CL between the homologous antigen (69% for Lb) and the heterologous antigen (42% for Lc). However, this difference was not significant in sera from dogs with VL (61% for Lb and 73% for Lc). No significant staining was observed in control sera (0.6% for Lb and 0.4% for Lc) consisting of samples from healthy dogs, or in the group with sporotrichosis (1.8% for Lb and 1.5% for Lc), a differential diagnosis of CL. The results suggest that flow cytometry might be useful for the differentiation between CL and VL in dogs, with practical applications in areas where the two infections overlap.
Subject(s)
Dog Diseases/diagnosis , Immunoglobulin G/blood , Leishmania/classification , Leishmaniasis, Cutaneous/veterinary , Leishmaniasis, Visceral/veterinary , Animals , Antibodies, Protozoan , Antigens, Protozoan , Dog Diseases/immunology , Dog Diseases/parasitology , Dogs , Flow Cytometry/veterinary , Leishmaniasis, Cutaneous/immunology , Leishmaniasis, Cutaneous/parasitology , Leishmaniasis, Visceral/immunology , Leishmaniasis, Visceral/parasitology , Species SpecificityABSTRACT
INTRODUCTION: Favorable responses in American tegumentary leishmaniasis (ATL) patients to treatment with 5 mg Sbv/kg/day meglumine antimoniate (MA) has been reported in Rio de Janeiro, but little is known regarding the therapeutic response to low doses in patients from other locations. METHODS: A retrospective review of medical records was conducted to compare the therapeutic response to 5 mg Sbv/kg/day MA treatment among 36 patients who acquired ATL in Brazilian states other than Rio de Janeiro (OS group) and 72 patients from Rio de Janeiro (RJ group). RESULTS: One course of 5 mg Sbv/kg/day MA cured 72.8% of 81 cutaneous (CL) and 66.6% of 27 mucosal (ML) leishmaniasis-infected patients: 70% in the CL/RJ group, 81% in the CL/OS group, 50% in the ML/RJ group, and 80% in the ML/OS group. After up to two additional treatment courses at the same dose, 88.9% and 85.2% of the CL and ML patients were cured, respectively. Adverse events were observed in 40% of patients in the CL/RJ group, 57% of the CL/OS group, 58% of the ML/RJ group, and 80% of the ML/OS group. No significant differences were observed in the cure rates or adverse effects between the RJ and OS groups. No patients required permanent discontinuation of treatment due to adverse events. CONCLUSIONS: Patients with ATL acquired in both RJ and OS may respond to low-dose MA. While high-dose MA should remain the standard treatment for ATL, low-dose MA might be preferred when toxicity is a primary concern.
Subject(s)
Antiprotozoal Agents/therapeutic use , Leishmaniasis, Cutaneous/drug therapy , Meglumine Antimoniate/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Brazil , Child , Child, Preschool , Female , Geography , Humans , Infant , Infant, Newborn , Leishmaniasis, Cutaneous/parasitology , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
Rheumatoid arthritis (RA) is a chronic condition that is frequent in patients living in tropical areas exposed to leishmaniasis. RA therapy involves immunosuppressant drugs such as methotrexate (MTX), monoclonal antibodies (mAbs) and prednisone. We report an unusual presentation of cutaneous (CL) or mucocutaneous leishmaniasis (ML) in RA patients from an endemic area of leishmaniasis. A 51-year-old woman noted a cutaneous ulcer on her left ankle during MTX and prednisone RA therapy. Initially diagnosed as a venous stasis ulcer, the aspirate of the injury revealed the presence of Leishmania DNA. A 73-year-old woman presenting non-ulcerated, infiltrated and painful erythematous nodules inside her nostrils while receiving MTX, anti-TNF mAb, and prednisone for RA, had also the aspirate of injuries showing the presence of Leishmania DNA. Both patients healed after the therapy with liposomal amphotericin. The RA therapy has changed to low-dose prednisone, without further reactivation episodes. Both cases suggest that CL or ML can reactivate after administration of an immunosuppressant for RA treatment. Therefore, immunosuppressive treatments for RA should be carefully prescribed in patients from endemic areas or with a history of CL and ML.
Subject(s)
Antirheumatic Agents/adverse effects , Immunosuppressive Agents/adverse effects , Leishmania/isolation & purification , Leishmaniasis, Cutaneous/etiology , Aged , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/immunology , DNA, Protozoan/analysis , Female , Humans , Immunosuppressive Agents/therapeutic use , Leishmania/genetics , Leishmaniasis, Cutaneous/diagnosis , Leishmaniasis, Mucocutaneous/immunology , Middle Aged , RecurrenceABSTRACT
ABSTRACT The municipality of Paracambi (Rio de Janeiro, Brazil) reports sporadic cases of American cutaneous leishmaniasis (ACL). Previous studies detected Nyssomyia intermedia (Diptera: Psychodidae) as the main vector in the region, but its spatial distribution and the presence of other vector species have not been evaluated. This study aims at filling this knowledge gap, by studying the ecology of sand flies, their spatiotemporal distribution, and correlation with land use/cover. Two campaigns of monthly sand fly collections using light traps and manual captures were conducted in 1992-1994 and 2001-2003. Females were dissected to detect natural Leishmania infections. The spatial distribution of sand flies was assessed using kernel density maps. Correlations with land use/cover were evaluated by extracting satellite imagery data around the capture points. A total of 17,232 sand flies from 13 species were captured. Medically important species included Ny. intermedia, Migonemyia migonei, Pintomyia fischeri and Ny. whitmani. No Leishmania-infected females were detected. Highest densities were detected in the peri-urban areas Cascata and Sabugo, and in rural areas São José and Mutirão. Ny. intermedia had statistically significant correlations with pasture and agricultural areas. Present results strengthened that Ny. intermedia and Mg. migonei are the main local ACL vectors. Correlations with land use evidence the association between ACL and anthropic environmental change.
ABSTRACT
Eighty-nine patients with clinical suspicion of leishmaniasis were referred for differential diagnosis. Sporothrix schenckii sensu lato was isolated in Novy-MacNeal-Nicolle + Schneider media in 98% of 64 patients with final diagnosis of sporotrichosis. This medium may be suitable for diagnosis of sporotrichosis in areas where cutaneous leishmaniasis is also endemic.
Subject(s)
Culture Media/chemistry , Leishmaniasis, Cutaneous/diagnosis , Microbiological Techniques/methods , Skin/microbiology , Sporothrix/isolation & purification , Sporotrichosis/diagnosis , Diagnosis, Differential , HumansABSTRACT
Although New World cutaneous leishmaniasis is not itself a life-threatening disease, its treatment with systemic antimonials can cause toxicity that can be dangerous to some patients. Intralesional meglumine antimoniate provides a viable, less toxic alternative. Herein, we describe an alternative treatment with subcutaneous intralesional injections of meglumine antimoniate into large periarticular lesions of three patients with cutaneous leishmaniasis and comorbidities. This treatment was safe, successful, and well tolerated. This case series suggests that intralesional meglumine antimoniate is an effective therapy for cutaneous leishmaniasis, even with periarticular lesions. This hypothesis should be tested in controlled clinical trials.
Subject(s)
Antiprotozoal Agents/administration & dosage , Leishmaniasis, Cutaneous/drug therapy , Meglumine/administration & dosage , Organometallic Compounds/administration & dosage , Aged , Female , Humans , Injections, Intralesional , Male , Meglumine Antimoniate , Middle Aged , Severity of Illness Index , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Although high dose of antimony is the mainstay for treatment of American cutaneous leishmaniasis (ACL), ongoing major concerns remain over its toxicity. Whether or not low dose antimony regimens provide non-inferior effectiveness and lower toxicity has long been a question of dispute. METHODS: A single-blind, non-inferiority, randomized controlled trial was conducted comparing high dose with low dose of antimony in subjects with ACL treated at a referral center in Rio de Janeiro, an endemic area of Leishmania (Viannia) braziliensis transmission. The primary outcome was clinical cure at 360 days of follow-up in the modified-intention-to-treat (mITT) and per-protocol (PP) populations. Non-inferiority margin was 15%. Secondary objectives included occurrence of epithelialization, adverse events and drug discontinuations. This study was registered in ClinicalTrials.gov: NCT01301924. RESULTS: Overall, 72 patients were randomly assigned to one of the two treatment arms during October 2008 to July 2014. In mITT, clinical cure was observed in 77.8% of subjects in the low dose antimony group and 94.4% in the high dose antimony group after one series of treatment (risk difference 16.7%; 90% CI, 3.7-29.7). The results were confirmed in PP analysis, with 77.8% of subjects with clinical cure in the low dose antimony group and 97.1% in the high dose antimony group (risk difference 19.4%; 90% CI, 7.1-31.7). The upper limit of the confidence interval exceeded the 15% threshold and was also above zero supporting the hypothesis that low dose is inferior to high dose of antimony after one series of treatment. Nevertheless, more major adverse events, a greater number of adverse events and major adverse events per subject, and more drug discontinuations were observed in the high dose antimony group (all p<0.05). Interestingly, of all the subjects who were originally allocated to the low dose antimony group and were followed up after clinical failure, 85.7% achieved cure after a further treatment with local therapy or low dose of antimony. CONCLUSIONS: Compared with high dose, low dose of antimony was inferior at the pre-specified margin after one series of treatment of ACL, but was associated with a significantly lower toxicity. While high dose of antimony should remain the standard treatment for ACL, low dose antimony treatment might be preferred when toxicity is a primary concern.