Hypertrophic cervical spinal cord pachymeningitis due to Treponema pallidum infection.

Neurosyphilis is recognized as a potential cause of hypertrophic pachymeningitis, but modern reports are few. A middle-aged man presented to hospital with a 1 month history of lower limb pain and weakness. Cerebrospinal fluid analysis showed pleocytosis with high protein levels and a positive venereal disease research laboratory result. Cervical spinal cord resonance imaging disclosed a dural contrast enhancement suggestive of pachymeningitis. Biopsy of the dura mater revealed a thick inflammatory process. Despite being treated accordingly, the patient rapidly deteriorated and died. The patient was diagnosed as having subacute hypertrophic cervical pachymeningitis which caused spinal cord compression. Serological evidence of neurosyphilis was present. Physicians should still be aware of this cause of hypertrophic pachymeningitis.

Impact assessment of different DNA extraction methods for non-invasive molecular diagnosis of tegumentary leishmaniasis.

The aim of this study was to evaluate two methods of nucleic acid extraction (spin-column-based method - commercial kit and direct boil - DB) from swab sampling compared to biopsy sampling for the diagnosis of tegumentary leishmaniasis (TL), (cutaneous - CL and mucocutaneous - MCL forms). The impact of these nucleic acid extraction protocols on different types of PCR and LAMP techniques were compared regarding nucleic acid quality, molecular assays accuracy, indirect quantitation, and costs. The evaluated patients were 57 TL cases (36 CL and 21 MCL) and 34 non-cases. Swab samples extracted by the DB method showed a higher DNA degradation rate and worse DNA quality in comparison to the commercial kit. Molecular tests performed on biopsy samples showed identical or higher performance in all analysis, as compared to their own performance on swab samples for TL (CL and MCL). However, only the SSU rRNA TaqMan™ RT-PCR test showed a significant difference between the performance of biopsy and swab samples extracted by commercial kit. The kDNA-cPCR coupled with swab extracted by commercial kit showed the highest accuracy (95.6%) for TL diagnosis. The sensitivity of the LAMP-RT 18S method in swab samples extracted with a commercial kit (82.5%) was close to that found in biopsy samples (86%) for TL diagnosis. The DB extraction method presented the lowest cost. The use of swab as a minimally-invasive sampling method, associated with an efficient nucleic acid extraction protocol, may represent a low-cost alternative for the diagnosis of CL and MCL.

Economic impact of localized cutaneous leishmaniasis on adult patients of a referral service in Belo Horizonte, Minas Gerais State, Brazil.

Cutaneous leishmaniasis (CL) is a disease associated with low-income populations. Thus, in assessing the burden of this disease, it is important to include its economic impact on individuals. We aimed to evaluate CL economic impact on patients treated at a referral service in the State of Minas Gerais, Brazil. This is a cross-sectional study based on the analysis of interviews and medical records from which we assembled direct medical and non-medical costs related to CL, from a societal perspective. One hundred patients were included; 50% had a monthly per capita income of up to USD 259.60 and spent on average USD 187.32 with the disease, representing an average monthly impact of 22.5% (USD 133.80). The disease imposed direct medical costs, such as: private medical appointments, medications, medical exams, dressing material, and co-participation in health insurances. Direct non-medical costs were mainly related to patients' transportation to health centers (USD 4,911.00), but also included medically-necessary care, food, and domestic and business outsourcing services. Although the Brazilian public health system guarantees access to health care, CL still represents a substantial economic impact for patients. The main action to reduce the expenses with this disease is decentralizing services for CL diagnosis and therapeutic approach, as well as increasing their efficiency.

Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV/AIDS Patients.

Background: Visceral leishmaniasis/HIV-co-infected patients (VL/HIV) accounts for around 8% of VL reported cases in Brazil. Relapses of Leishmania infection after anti-leishmanial treatment constitute a great challenge in the clinical practice because of the disease severity and drug resistance. We have shown that non-relapsing-VL/HIV (NR-) evolved with increase of CD4+ T-cell counts and reduction of activated CD4+ and CD8+ T cells after anti-leishmanial treatment. This immune profile was not observed in relapsing-VL/HIV patients (R-), indicating a more severe immunological compromising degree. Elevated activation status may be related to a deficient immune reconstitution and could help to explain the frequent relapses in VL/HIV co-infection. Our aim was to evaluate if this gain of T cells was related to changes in the peripheral TCRVß repertoire and inflammatory status, as well as the possible thymus involvement in the replenishment of these newly formed T lymphocytes. Methods: VL/HIV patients, grouped into non-relapsing (NR- = 6) and relapsing (R- = 12) were evaluated from the active phase up to 12 months post-treatment (mpt). HIV-infected patients (non-VL) and healthy subjects (HS) were included. The TCRVß repertoire was evaluated ex vivo by flow cytometry, whereas the plasmatic cytokine levels were assessed by Luminex assay. To evaluate the thymic output, DNA was extracted from PBMCs for TCR rearrangement excision circles (TREC) quantification by qPCR. Results: VL/HIV cases presented an altered mobilization profile (expansions or retractions) of the TCRVß families when compared to HS independent of the follow-up phase (p < 0.05). TCRVß repertoire on CD4+ T-cells was more homogeneous in the NR-VL/HIV cases, but heterogeneous on CD8+ T-cells, since different Vß-families were mobilized. NR-VL/HIV had the inflammatory pattern reduced after 6 mpt. Importantly, VL/HIV patients showed number of TREC copies lower than controls during all follow-up. An increase of recent thymic emigrants was observed in NR-VL/HIV individuals at 10 mpt compared to R- patients (p < 0.01), who maintained lower TREC contents than the HIV controls. Conclusions: VL/HIV patients that maintain the thymic function, thus generating new T-cells, seem able to replenish the T lymphocyte compartment with effector cells, then enabling parasite control.

Patients' preferences of cutaneous leishmaniasis treatment outcomes: Findings from an international qualitative study.

BACKGROUND: Cutaneous leishmaniasis (CL) is a disease that often affects exposed skin areas and may heal leaving lifelong scars. Patients' expectations from treatment are rarely considered in drug development for CL. An initiative aiming to address shortcomings in clinical trial design and conduct for CL treatments involving the researchers' community is on-going. This manuscript presents patient-preferred outcomes for CL and an assessment on how to consider these in the conduct of future trials. METHODOLOGY/PRINCIPAL FINDINGS: We report preferred treatment outcomes by 74 patients with confirmed CL in endemic regions of Brazil, Burkina Faso, Colombia, Iran, Morocco, Peru and Tunisia during individual in-depth interviews. Beyond outcomes customarily considered in trials (such as lesion appearance and adverse events), patients talked about a large number of outcomes related to quality of life, such as pain, scar formation, and others affecting their work and daily activities. They also reported fears around getting rid of the parasite, disease recurrence, and possible sequelae. CONCLUSIONS/SIGNIFICANCE: The study results provide a rich insight into important outcomes for CL treatments, as well as related topics, from the perspective of a diverse patient population. Among the outcomes identified, we argue that those related to quality of life as well as recurrence should be included to a greater extent for assessment in clinical trials, and discuss the suitability of measurement instruments such as the Dermatology Quality of Life Index (DLQI). Interviews also point out the potential need to address concerns related to parasitological cure or scar formation, such as social stigmatization and disability. In addition, patients should be given information in order to clarify reported misconceptions. This study therefore suggests a methodology for consulting CL patients on outcomes as elements of clinical trial design, and how to incorporate these outcomes in trials. It also discusses how reported outcomes could be addressed in clinical care.

How cutaneous leishmaniasis and treatment impacts in the patients' lives: A cross-sectional study.

BACKGROUND: Until now, few studies have evaluated the effect of cutaneous leishmaniasis (CL) on patients' quality of life, and none have used a specific instrument to measure this effect. The objective of this study was to identify factors that may be associated with the high impact of CL and to assess patients' satisfaction with treatment and health services by utilizing a disease-specific questionnaire. METHODOLOGY: Between December 2015 and May 2017, 100 patients with localized cutaneous leishmaniasis were interviewed at a leishmaniasis referral center in Brazil. Data were collected by two questionnaires. One questionnaire compiled the sociodemographic, economic, and clinical information related to the disease. The second questionnaire was the Cutaneous Leishmaniasis Impact Questionnaire (CLIQ), which consisted of two subscales that measured 1) the general impact of CL and 2) patients' perceptions of treatment and health services. The median scores from each of these two subscales were used to dichotomize the dependent variables. Risk factors for the high impact of CL and for low patient satisfaction with treatment and health services were analyzed with a logistic regression analysis. RESULTS: The chance of higher impact of CL was increased in patients with the presence of comorbidities (OR: 3.9; CI 1.25-12.36), in those with absences from work (OR: 12.0; CI 3.78-42.55), in those who relied on public transportation by a municipal bus (OR: 5.8; CI 1.27-26.77), and in those who had illness-related expenses greater than U$137 (OR: 3.5; CI 1.17-10.24). The chance of patient dissatisfaction with treatment and health services increased with higher education (OR: 5.0; CI 1.19-21.03) and with illness-related expenses exceeding U$137 (OR: 4.64; CI 1.49-14.48). Once the sample was non-probabilistic, findings are not representative of CL patients in general. CONCLUSIONS: CL and its treatment have a negative impact on patients' quality of life. Considering these effects during public health planning may help patients to confront the disease.

Development and initial validation of a cutaneous leishmaniasis impact questionnaire.

BACKGROUND: The impact of cutaneous leishmaniasis (CL) on the quality of life of patients has been neglected in research studies worldwide. The few reported studies have used non-specific questionnaires for the disease, which represents a limitation since generic instruments may not address specific aspects of the disease, compromising the evaluation of its real impact. The aim of this paper is to describe the development and the initial validation of an instrument for evaluating the impact of CL, named the Cutaneous Leishmaniasis Impact Questionnaire. METHODOLOGY: The formulation and validation of the instrument consisted of the following steps: (1) literature review; (2) conceptual framework construction and initial item generation; (3) tool analysis by health professionals (experts); (4) tool evaluation performed by the patients; and (5) a pilot study with 100 patients with localized CL, evaluated at a reference ambulatory facility in Belo Horizonte, in the state of Minas Gerais, Brazil. The structure of the proposed instrument was analyzed using hierarchical cluster analysis (ICLUST). RESULTS: Twenty-seven items were initially proposed by the researchers to compose the questionnaire. Content validity (evaluates if the instrument fully assesses the construct of interest) was evaluated by the panel of experts, while face validity (evaluates how potential participants interpret the items) was evaluated by the target population. In this step, some items were excluded, reformulated and/or included. After evaluating a factorial structure of the items in accordance with the cluster analysis, we assembled a questionnaire with 25 items (alpha = 0.86), with high reliability and homogeneity, which address the following: 1) the general impact of the disease (alpha = 0.91, beta = 0.67) and 2) the evaluation of the perception about the treatment and health services (alpha = 0.72, beta = 0.51). CONCLUSIONS: The Cutaneous Leishmaniasis Impact Questionnaire, developed with contributions from patients and experts, was confirmed, in this first validation, as a useful and reliable instrument.

An international qualitative study exploring patients' experiences of cutaneous leishmaniasis: study set-up and protocol.

INTRODUCTION: Lack of investments in drug development, lack of standardisation of clinical trials and the complexity of disease presentations contribute to the current lack of effective, safe and adapted treatments for cutaneous leishmaniasis (CL). One aspect concerns outcomes affecting patients' quality of life (QoL): these are hardly assessed in trials, despite potential functional and/or aesthetic impairment caused by CL, which typically affects disadvantaged and vulnerable people living in rural areas. Here, we describe the approach used to bring perspectives of patients with CL into designing and assessing treatments. METHODS AND ANALYSIS: This international qualitative study uses interviews with patients to explore their experiences with CL to (1) elicit outcomes and eligibility criteria for clinical trials important to them and (2) to better understand their needs and views about the disease and their requirements and expectations from treatment. Here, we describe the set-up of this collaborative study and the protocol. Data collection is ongoing.The protocol includes study design, preparation, conduct and analysis of individual interviews with approximately 80 patients in seven countries (Burkina Faso, Brazil, two sites in Colombia, Iran, Morocco, Peru and Tunisia) where CL is prevalent. Principal investigators and sites were selected through an open call, and two workshops were organised for protocol development and training in conduct and analysis of qualitative health research. Patient recruitment aims at covering a maximum variation of experiences. Transcripts will be analysed to identify outcomes and eligibility criteria as well as further topics that are expected to emerge from the interviews, such as direct and indirect costs related to CL, its psychological impact, preferred modes of drug administration and traditional treatments. ETHICS AND DISSEMINATION: The study received ethical approval by the responsible committees of each of the participating institutions. Findings will be disseminated through publication in peer-reviewed journals, scientific meetings and to participants and their communities.

Efficacy of pentavalent antimoniate intralesional infiltration therapy for cutaneous leishmaniasis: A systematic review.

BACKGROUND: The mainstays of cutaneous leishmaniasis (CL) treatment, in several world regions, are pentavalent antimony (Sbv) compounds administered parenterally, despite their recognized toxicity, which requires frequent laboratory monitoring and complicates their use in areas with scarce infrastructure. As result of these drawbacks, the WHO Expert Committee on leishmaniasis has expanded the recommendations for the use of local therapies, including Sbv intralesional infiltration (IL-Sbv), as CL therapy alternatives even in the New World. However, the efficacy of these approaches has never been compiled. The aim of this study was to critically and systematically assess the efficacy of IL-Sbv for CL treatment. METHODOLOGY: The PRISMA guidelines for systematic reviews and the Cochrane manual were followed. The sources used were the MEDLINE and LILACS databases and the International Clinical Trials Registry Platform of the World Health Organization. The outcome of interest was a clinical cure, defined as complete re-epithelialization of all lesions. The IL-Sbv pooled cure rate was estimated for several subgroups and direct comparisons were performed when possible. RESULTS: Thirty nine articles (40 studies) involving 5679 patients treated with IL-Sbv infiltration were included. In direct comparison, only three studies involving 229 patients compared IL-Sbv infiltration versus placebo and no difference was observed (OR: 1,9; 95%IC 0,93 to 3,82) based on cure rate 69.6% (95%CI 17.6-96.1%) and 83,2% (95%CI 66-92.7%) for placebo and IL-Sbv, respectively. In an alternative and non-comparative analysis, gathering all study arms using the intervention, the pooled IL-Sbv efficacy rate was 75% (95%CI 68-81%). In the Old World, the observed overall IL-Sbv efficacy rate was 75% (95%CI 66-82%), and the cure rates were significantly higher with sodium stibogluconate (SSG) than with meglumine antimoniate (MA): 83% (95%CI 75-90%) versus 68% (95%CI 54-79%), p = 0.03. Studies directly comparing IL-Sbv with topical 15% paromomycin ointment, IL hypertonic saline, radiofrequency-induced heat therapy, topical trichloroacetic acid and cryotherapy showed no significant difference in efficacy between the interventions. The analyses suggested a higher efficacy of IL-Sbv combined with cryotherapy (81.8%, 95%IC 62.4-92.4%) when compared with IL-Sbv alone (53.3%, 95%IC 46.1-66%), OR: 3.14 (95%CI 1.1-8.9), p = 0.03. In the New World, the global IL-Sbv efficacy was 77%(95%CI 66-85%). In contrast with the Old World, a significant difference favoring MA in relation to SSG was observed: 61% (95%CI 49-73%) versus 82% (95%CI 70-89%).By comparing IL infiltration schedules, it was determined that patients submitted to IL-Sbv treatments longer than 14 days had higher cure rates. CONCLUSIONS: Despite the high heterogeneity and low methodological quality of studies, an indirect comparison shows that the antimony infiltration efficacy rate is similar to that reported for antimony systemic use. The evidence gathered thus far is insufficient to identify the ideal IL therapeutic regime or estimate the rates of adverse events and mucosal late complications.

Efficacy of azole therapy for tegumentary leishmaniasis: A systematic review and meta-analysis.

BACKGROUND: Several controlled and uncontrolled studies addressing azole antifungal drugs for cutaneous and mucosal leishmaniasis have been published with inconclusive results. We conducted a systematic literature review of studies evaluating the efficacy and toxicity associated with azole therapy for tegumentary leishmaniasis. METHODOLOGY: PRISMA guidelines for systematic reviews and the Cochrane manual were followed, and the review methodology was registered (PROSPERO; CRD42016048668). Sources included the EMBASE, Web of Science, MEDLINE, LILACS, and IBECS databases along with a manual search of references from evaluated studies. Additional resources such as Google Scholar and clinicaltrials.gov were also searched. We included all studies reporting cure rate after cutaneous or mucosal leishmaniasis treatment with systemic azole drugs, regardless of their design. R software was used to estimate global rates of success and adverse events with each drug. The main outcome of interest was clinical cure, defined as complete re-epithelialization of all lesions. RESULTS: A total of 37 studies involving 1259 patients that reported outcomes after fluconazole (9), ketoconazole (14) and itraconazole (15) treatments were included. Only 14 (38%) were randomized controlled trials (RCT). The pooled azole final efficacy rate was 64% (CI95%: 57-70%) for all studies and 60% (CI95%: 50-70%) (p = 0.41) if only RCTs studies were considered. Twenty-four studies were conducted in the Old World and 13 studies in the Americas. The final efficacy rate according to New and Old World were 62% (CI95%: 43-77%) and 66% (CI95%: 58-73%), respectively. The final efficacy rate of azoles according to species were 89% (CI95%: 50-98%) for L. mexicana; 88% for L. infantum (CI95%: 27-99%); 80% for L. donovani; 53% (CI95%: 29-76%) for L. major; 49% for L. braziliensis (CI95%: 21-78%); and 15% (CI95%: 1-84%) for L. tropica. The cure rates were similar among the fluconazole, ketoconazole and itraconazole group arms (p = 0.89), specifically 61% (CI95%: 48-72%), 64% (CI95%: 44-80%) 65% (CI95%: 56-72%), respectively. Adverse events during fluconazole, itraconazole and ketoconazole therapy were reported in 7% (CI95%: 3-14%), 12% (CI95% 8-19%) and 13% (CI95%: 6-29%) of treated patients, respectively, without difference among them (p = 0.35). This systematic review included studies with small samples and both non-comparative and non-randomized studies and the main limitation was the low quality of the available studies. CONCLUSIONS: Available evidence suggests that fluconazole, ketoconazole and itraconazole have similar and modest efficacy rates for tegumentary leishmaniasis treatment. There is insufficient evidence to support the exclusive use of azole therapy as a single agent for leishmaniasis treatment.

Exploring prognosis in chronic relapsing visceral leishmaniasis among HIV-infected patients: Circulating Leishmania DNA.

BACKGROUND: Visceral leishmaniasis (VL) affecting HIV-infected patients is considered a challenging condition because of its high mortality and relapse rates. The approach of this condition is still surrounded by many uncertainties, especially regarding the criteria to institute and discontinue secondary prophylaxis for VL. The aim of this study was to evaluate the Leishmania parasitism kinetic assessed by polymerase chain reaction (PCR) as a possible tool in the prognostic assessment in a context in which patients are receiving highly active antiretroviral therapy and secondary prophylaxis. METHODS: A prospective observation of Leishmania-HIV-co infected patients was performed and two groups with distinct clinical prognosis unpredicted by their CD4 count at the moment of VL diagnosis and not related to their HIV load control were confirmed. RESULTS: Relapsing (R) and non-relapsing (NR) patients had similar antiviral therapy use rates, CD4 lymphocyte count medians and HIV load levels at VL-diagnosis. At the 12-month follow-up, R-patients presented a significantly lower CD4 lymphocyte count than NR-patients, without difference in HIV load control. The time between HIV and VL diagnoses was longer in the R than NR-group. Comparison between Kaplan-Meier relapse-free survival curves (time to relapse) using a log rank test showed that patients presenting circulating Leishmania DNA had a significantly higher risk of clinical VL relapse within 4 months after a positive test (p=0.001). CONCLUSIONS: These results reinforce that a negative PCR could be a useful tool to support prophylaxis interruption among patients with CD4 counts above 200cells/mm3 and that a positive PCR suggests imminent VL relapse.

Preoperative bathing of the surgical site with chlorhexidine for infection prevention: Systematic review with meta-analysis.

BACKGROUND: Preoperative bathing with 4% chlorhexidine is recommended as a measure to prevent surgical site infection (SSI) despite uncertainty regarding the effectiveness of the intervention. This review aimed to assess the effect of bathing with 4% chlorhexidine on the prevention of SSIs in clean surgeries compared with bathing with placebo solution or soap. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews and the Cochrane manual were followed. Sources were MEDLINE and Latin American and Caribbean Health Sciences Literature databases and manual search of references from evaluated studies. We included randomized studies evaluating clean surgical wounds and reporting SSIs after preoperative bathing with 4% chlorhexidine. RESULTS: A total of 243 primary studies were identified and 8 were considered methodologically appropriate based on the Jadad Scale. Data were gathered from 10,655 patients. The global SSI rate was 7.2%. The SSI rate for chlorhexidine bathing, placebo, and soap without antiseptic groups was 7.1%, 9.1%, and 5.1%, respectively. A significant reduction in the infection rates was not found in the comparison between patients subjected to preoperative bathing with 4% chlorhexidine versus placebo solution (relative risk, 0.91; 95% confidence interval, 0.76-1.09). The same absence of benefit was observed comparing chlorhexidine bathing with soap (relative risk, 1.06; 95% confidence interval, 0.68-1.66). CONCLUSIONS: Controlled clinical trials are needed to assess the effect of preoperative chlorhexidine bathing on infection rates following clean surgery before the incorporation of this intervention in health care services.

Development and Validation of a PCR-ELISA for the Diagnosis of Symptomatic and Asymptomatic Infection by Leishmania (Leishmania) infantum.

A kDNA PCR enzyme-linked immunosorbent assay (kDNA PCR-ELISA) for the diagnosis of human visceral leishmaniasis (HVL) was developed. The detection limit of the reaction, precision measurements, and cut-off of the kDNA PCR-ELISA were defined in a proof-of-concept phase. A reference strain of Leishmania (Leishmania) infantum and a bank of 14 peripheral blood samples from immunocompetent patients with VL were characterized using techniques considered gold standards, and 11 blood samples obtained from healthy individuals of an endemic area were also assessed. Phase II evaluation determined the performance of the assay in peripheral blood samples from 105 patients with VL (adults and children), 25 patients with Leishmania/HIV coinfection, 40 healthy individuals, and 33 asymptomatic individuals living in endemic areas. The kDNA PCR-ELISA exhibited satisfactory precision, with a detection limit of 0.07 fg of DNA from L. (L.) infantum and 1 parasite/mL blood. The overall sensitivity of the assay for all groups studied was 100% (95% confidence interval [CI]: 97.1-100%), and the specificity was 95% (95% CI: 83.5-98.6%). The kDNA PCR-ELISA was shown to be a useful tool for VL symptomatic and asymptomatic individuals diagnosis and its use in endemic countries may help monitor control interventions.

Ultrasound and clinical investigation of hepatosplenic schistosomiasis: evaluation of splenomegaly and liver fibrosis four years after mass chemotherapy with oxamniquine.

The course of hepatosplenic schistosomiasis after mass chemotherapy with oxamniquine has been rarely reported. We report the effect of treatment in patients with advanced schistosomiasis mansoni living in area of Brazil highly endemic for this disease. A total of 739 inhabitants of a village were subjected to clinical and abdominal ultrasound examinations and were treated with oxamniquine. We have identified 84 individuals with hepatosplenic schistosomiasis. Alcohol abuse was associated with periportal thickening. Four years after treatment, 42 of the 84 individuals were re-examined and regression of splenomegaly was observed in 59% and of periportal thickening in 32%. Our data indicate that mass chemotherapy can lead to reduction of schistosomiasis morbidity but a significant group of patients (68%) will not improve. The association with alcohol abuse should be further evaluated. Thickening of the gallbladder wall can be a useful predictor of no involution of liver fibrosis after treatment.

The Cure Rate after Placebo or No Therapy in American Cutaneous Leishmaniasis: A Systematic Review and Meta-Analysis.

INTRODUCTION: There are few drugs with proven efficacy in cutaneous leishmaniasis (CL), and pentavalent antimonial derivatives are still the main first-line therapeutic agents worldwide, despite their recognized high toxicities. Randomized controlled clinical trials assessing the efficacy and safety of new therapeutic modalities are of high priority, and the definition of the design of such trials raises debate about the use of placebo as a comparator. To support the use of placebo as a comparator, two main points need to be addressed: 1--the cure rate without any therapeutic intervention and 2--the damage caused by CL and its impact on patients. OBJECTIVE: The aim of this study was to systematically assess the spontaneous cure rate for American CL and to broaden the discussion about placebo use in CL trials. METHODS: The PRISMA guidelines for systematic reviews and the Cochrane manual were followed. The sources used were the PubMed and LILACS databases. Studies were included if they reported cure rates using placebo or no treatment in American CL. RESULTS: Thirteen studies of a total of 352 patients were ultimately included in this review. The summarized global cure rates for all Leishmania species according to the intention-to-treat analyses performed at approximately three ("initial cure") and nine ("definitive cure") months after "no treatment" or placebo use were 26% (CI95%: 16 to 40%) and 26% (CI95%:16 to 38%), respectively. Notably, a significantly lower cure rate was observed for L. braziliensis infection (6.4%, CI95%:0.2 to 20%) than for L. mexicana infection (44%, CI95%:19 to 72%), p = 0.002. Of note, relapse occurred in 20% of patients with initial healing (CI95%:9.2 to 38.9%). CONCLUSION: These results clearly demonstrate a low spontaneous cure rate following no-treatment or placebo use, confirming that this strategy for the control group in CL studies expose patients to greater morbidity, especially for CL caused by L. braziliensis. Therefore, from this point, the crucial question to consider regarding placebo use is the seriousness of the suffering caused by this disease.

Immune Activation and Bacterial Translocation: A Link between Impaired Immune Recovery and Frequent Visceral Leishmaniasis Relapses in HIV-Infected Patients.

The maintenance of chronic immune activation due to leishmaniasis or even due to microbial translocation is associated with immunosenescence and may contribute to frequent relapses. Our aim was to investigate whether patients with HIV-associated visceral leishmaniasis (VL/HIV) who experience a single episode of VL have different immunological behaviors in comparison to those who experience frequent relapses. VL/HIV patients were allocated to non-relapsing (NR, n = 6) and relapsing (R, n = 11) groups and were followed from the active phase of VL up to 12 months post-treatment (mpt). The patients were receiving highly active antiretroviral therapy (HAART) and secondary prophylaxis after VL therapy. During active VL, the two groups were similar in all immunological parameters, including the parasite load. At 6 and 12 mpt, the NR group showed a significant gain of CD4+ T cells, a reduction of lymphocyte activation, and lower soluble CD14 and anti-Leishmania IgG3 levels compared to the R group. The viral load remained low, without correlation with the activation. The two groups showed elevated but similar percentages of senescent T cells. These findings suggest a decreased ability of the R group to downmodulate immune activation compared to the NR group. Such functional impairment of the effector response may be a useful indicator for predicting clinical prognosis and recommending starting or stopping secondary prophylaxis.

Economic impact of localized cutaneous leishmaniasis on adult patients of a referral service in Belo Horizonte, Minas Gerais State, Brazil / Impacto econômico da leishmaniose cutânea localizada em pacientes adultos em um serviço de referência em Belo Horizonte, Minas Gerais, Brasil

A leishmaniose cutânea (LC) é uma doença associada a populações de baixa renda. Portanto, a inclusão do impacto financeiro sobre os pacientes é muito importante para avaliar a carga dessa doença. Tivemos como objetivo avaliar o impacto econômico da LC em pacientes afetados pela doença e tratados em um centro de referência para LC no Estado de Minas Gerais, Brasil. Foi um estudo transversal com base em análise de entrevistas e prontuários médicos para compilação dos gastos médicos e não médicos diretos relacionados à LC, desde uma perspectiva societal. Foram incluídos cem pacientes; 50% tinham renda mensal per capita de até USD 259,60. O gasto médio na doença foi de USD 187,32, o que representa um impacto mensal médio de 22,5% (USD 133,80). A doença impôs custos médicos diretos, como o pagamento por consultas médicas particulares, exames médicos, material para curativos e co-participação em seguro de saúde. Os custos não médicos diretos estiveram relacionados ao transporte dos pacientes até os centros de saúde, cuidados adicionais, alimentação e contratos com serviços terceirizados para atividades domésticas e laborais. O transporte dos pacientes para as consultas médicas representava a principal parcela dos gastos (USD 4.911,00). Embora o acesso à assistência à saúde seja um direito garantido pelo Sistema Único de Saúde, a LC ainda gera um impacto financeiro substancial para os pacientes. A descentralização dos serviços diagnósticos e terapêuticos para LC e o aumento de sua eficiência são as principais medidas que podem reduzir os gastos com essa doença.

Economic impact of localized cutaneous leishmaniasis on adult patients of a referral service in Belo Horizonte, Minas Gerais State, Brazil / Impacto econômico da leishmaniose cutânea localizada em pacientes adultos em um serviço de referência em Belo Horizonte, Minas Gerais, Brasil / Impacto económico de la leishmaniosis cutánea localizada que afecta a pacientes adultos en un servicio de referencia en Belo Horizonte, Minas Gerais, Brasil

Cutaneous leishmaniasis (CL) is a disease associated with low-income populations. Thus, in assessing the burden of this disease, it is important to include its economic impact on individuals. We aimed to evaluate CL economic impact on patients treated at a referral service in the State of Minas Gerais, Brazil. This is a cross-sectional study based on the analysis of interviews and medical records from which we assembled direct medical and non-medical costs related to CL, from a societal perspective. One hundred patients were included; 50% had a monthly per capita income of up to USD 259.60 and spent on average USD 187.32 with the disease, representing an average monthly impact of 22.5% (USD 133.80). The disease imposed direct medical costs, such as: private medical appointments, medications, medical exams, dressing material, and co-participation in health insurances. Direct non-medical costs were mainly related to patients' transportation to health centers (USD 4,911.00), but also included medically-necessary care, food, and domestic and business outsourcing services. Although the Brazilian public health system guarantees access to health care, CL still represents a substantial economic impact for patients. The main action to reduce the expenses with this disease is decentralizing services for CL diagnosis and therapeutic approach, as well as increasing their efficiency.

A leishmaniose cutânea (LC) é uma doença associada a populações de baixa renda. Portanto, a inclusão do impacto financeiro sobre os pacientes é muito importante para avaliar a carga dessa doença. Tivemos como objetivo avaliar o impacto econômico da LC em pacientes afetados pela doença e tratados em um centro de referência para LC no Estado de Minas Gerais, Brasil. Foi um estudo transversal com base em análise de entrevistas e prontuários médicos para compilação dos gastos médicos e não médicos diretos relacionados à LC, desde uma perspectiva societal. Foram incluídos cem pacientes; 50% tinham renda mensal per capita de até USD 259,60. O gasto médio na doença foi de USD 187,32, o que representa um impacto mensal médio de 22,5% (USD 133,80). A doença impôs custos médicos diretos, como o pagamento por consultas médicas particulares, exames médicos, material para curativos e co-participação em seguro de saúde. Os custos não médicos diretos estiveram relacionados ao transporte dos pacientes até os centros de saúde, cuidados adicionais, alimentação e contratos com serviços terceirizados para atividades domésticas e laborais. O transporte dos pacientes para as consultas médicas representava a principal parcela dos gastos (USD 4.911,00). Embora o acesso à assistência à saúde seja um direito garantido pelo Sistema Único de Saúde, a LC ainda gera um impacto financeiro substancial para os pacientes. A descentralização dos serviços diagnósticos e terapêuticos para LC e o aumento de sua eficiência são as principais medidas que podem reduzir os gastos com essa doença.

La leishmaniosis cutánea (LC) es una enfermedad asociada a poblaciones con ingresos bajos. Por ello, incluir el impacto financiero para las personas es muy importante a la hora de evaluar la carga de esta enfermedad. Nuestro objetivo fue evaluar el impacto económico de la LC, de pacientes afectados por esta enfermedad, que fueron tratados por un servicio de referencia para el tratamiento de la LC en el Estado de Minas Gerais, Brasil. Este estudio transversal basado en entrevistas y análisis de registros médicos para la recopilación de gastos médicos y no-médicos directos, relacionados con la LC desde una a perspectiva social. Se incluyeron a cien pacientes; el 50% contaba con ingresos mensuales per cápita de hasta USD 259,60 y gastaban un promedio de USD 187,32 en la enfermedad, representando un impacto promedio mensual de 22,5% (USD 133,80). La enfermedad supuso costes médicos directos, como el pago de citas médicas privadas, medicamentos, exámenes médicos, material para vendajes, y coparticipación en seguros médicos. Los costes directos no-médicos estaban relacionados con el transporte de los pacientes a los centros de salud, el cuidado necesario, comida, y contratos con servicios externalizados para actividades domésticas y laborales. El transporte de los pacientes para citas médicas representó la principal razón para los gastos (USD 4.911,00). A pesar de que el acceso a los cuidados de salud es un derecho garantizado por el sistema de salud público brasileño, la LC todavía supone un impacto financiero importante para los pacientes. La descentralización de los servicios para el diagnóstico de LC, la aproximación terapéutica, y el incremento de su eficiencia, son las acciones con principal potencial para reducir los gastos financieros de esta enfermedad.

Visceral leishmaniasis and HIV coinfection in Latin America.

Visceral leishmaniasis (VL) is an endemic zoonotic disease in Latin America caused by Leishmania (Leishmania) infantum, which is transmitted by sand flies from the genus Lutzomyia. VL occurs in 12 countries of Latin America, with 96% of cases reported in Brazil. Recently, an increase in VL, primarily affecting children and young adults, has been observed in urban areas of Latin America. The area in which this spread of VL is occurring overlaps regions with individuals living with HIV, the number of whom is estimated to be 1.4 million people by the World Health Organization. This overlap is suggested to be a leading cause of the increased number of reported VL-HIV coinfections. The clinical progression of HIV and L. infantum infections are both highly dependent on the specific immune response of an individual. Furthermore, the impact on the immune system caused by either pathogen and by VL-HIV coinfection can contribute to an accelerated progression of the diseases. Clinical presentation of VL in HIV positive patients is similar to patients without HIV, with symptoms characterized by fever, splenomegaly, and hepatomegaly, but diarrhea appears to be more common in coinfected patients. In addition, VL relapses are higher in coinfected patients, affecting 10% to 56.5% of cases and with a lethality ranging from 8.7% to 23.5% in Latin America, depending on the study. With regards to the diagnosis of VL, parasitological tests of bone marrow aspirates have proven to be the most sensitive test in HIV-infected patients. Serologic tests have demonstrated a variable sensitivity according to the method and antigens used, with the standard tests used for diagnosing VL in Latin America displaying lower sensitivity. For this review, few articles were identified that related to VL-HIV coinfections and originated from Latin America, highlighting the need for improving research within the regions most greatly affected. We strongly support the formation of a Latin American network for coinfections of Leishmania and HIV to improve the consistency of research on the current situation of VL-HIV coinfections. Such a network would improve the collection of vital data and samples for better understanding of the clinical manifestations and immunopathogenic aspects of VL in immunosuppressed patients. Ultimately, a concerted effort would improve trials for new diagnostic methodologies and therapeutics, which could accelerate the implementation of more specific and effective diagnosis as well as public policies for treatments to reduce the impact of VL-HIV coinfections on the Latin American population.