RESUMO
BACKGROUND: In Brazil, Leishmania (Leishmania) infantum is a widely distributed protozoan parasite. The human leishmaniasis caused by this species is often associated with visceral form. Tegumentary leishmaniasis (TL) cases due to L. (L.) infantum in the country are considered rare but may be underestimated. Although probably uncommon, these cases represent a new challenge to the prevention and control of leishmaniasis. OBJECTIVES: Here, we describe two distinct cases of TL with atypical clinical presentations caused by L. (L.) infantum. METHODS AND FINDINGS: Parasites were isolated from cutaneous lesions of the two patients and typed as L. (L.) infantum after sequencing of the ribosomal DNA internal transcribed spacer. The dermotropic L. (L.) infantum isolates were compared in terms of growth culture patterns, metacyclogenesis and in vitro infectivity in macrophages. MAIN CONCLUSIONS: This study addresses the emergence of L. (L.) infantum as a causative agent of cutaneous disease in a visceral leishmaniasis hotspot located in northeast Brazil. The data presented provides novel information about the presence of dermotropic L. (L.) infantum in the country and demonstrates the infectivity potential of theses isolates.
Assuntos
Leishmania infantum , Leishmaniose Cutânea , Humanos , Leishmania infantum/isolamento & purificação , Leishmania infantum/genética , Leishmaniose Cutânea/parasitologia , Brasil , Masculino , Feminino , DNA de Protozoário , Adulto , Reação em Cadeia da PolimeraseRESUMO
In Brazil, Leishmania amazonensis is the etiological agent of cutaneous and diffuse cutaneous leishmaniasis. The state of Maranhão in the Northeast of Brazil is prevalent for these clinical forms of the disease and also has high rates of HIV infection. Here, we characterized the drug susceptibility of a L. amazonensis clinical isolate from a 46-year-old man with diffuse cutaneous leishmaniasis coinfected with HIV from this endemic area. This patient underwent several therapeutic regimens with meglumine antimoniate, liposomal amphotericin B, and pentamidine, without success. In vitro susceptibility assays against promastigotes and intracellular amastigotes demonstrated that this isolate had low susceptibility to amphotericin B, when compared with the reference strain of this species that is considered susceptible to antileishmanial drugs. Additionally, we investigated whether the low in vitro susceptibility would affect the in vivo response to amphotericin B treatment. The drug was effective in reducing the lesion size and parasite burden in mice infected with the reference strain, whereas those infected with the clinical isolate and a resistant line (generated experimentally by stepwise selection) were refractory to amphotericin B treatment. To evaluate whether the isolate was intrinsically resistant to amphotericin B in animals, infected mice were treated with other drugs that had not been used in the treatment of the patient (miltefosine, paromomycin, and a combination of both). Our findings demonstrated that all drug schemes were able to reduce lesion size and parasite burden in animals infected with the clinical isolate, confirming the amphotericin B-resistance phenotype. These findings indicate that the treatment failure observed in the patient may be associated with amphotericin B resistance, and demonstrate the potential emergence of amphotericin B-resistant L. amazonensis isolates in an area of Brazil endemic for cutaneous leishmaniasis.
Assuntos
Anfotericina B , Antiprotozoários , Resistência a Medicamentos , Anfotericina B/farmacologia , Anfotericina B/uso terapêutico , Animais , Brasil , Pessoa de Meia-Idade , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Humanos , Masculino , Camundongos , Leishmania/efeitos dos fármacos , Leishmania/isolamento & purificação , Leishmania/classificação , Leishmania mexicana/efeitos dos fármacos , Leishmania mexicana/isolamento & purificação , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Testes de Sensibilidade Parasitária , Camundongos Endogâmicos BALB C , Leishmaniose Tegumentar Difusa/parasitologia , Leishmaniose Tegumentar Difusa/tratamento farmacológicoRESUMO
Objective: The objective of this study is to estimate the prevalence of chronic Chagas disease (CCD) in Brazil: in the general population, in women, and in women of childbearing age. Methods: A meta-analysis of the literature was conducted to extract data on the prevalence of CCD in municipalities in Brazil in the 2010-2022 period: in the general population, in women, and in women of childbearing age. Municipal-level CCD indicators available in health information systems were selected. Statistical modeling of the data extracted from the meta-analysis (based on data obtained from information systems) was applied to linear, generalized linear, and additive models. Results: The five most appropriate models were selected from a total of 549 models tested to obtain a consensus model (adjusted R2 = 54%). The most important predictor was self-reported CCD in the primary health care information system. Zero prevalence was estimated in 1 792 (32%) of Brazil's 5 570 municipalities; in the remaining 3 778 municipalities, average prevalence of the disease was estimated at 3.25% (± 2.9%). The number of carriers of CCD was estimated for the Brazilian population (~3.7 million), for women (~2.1 million) and for women of childbearing age (~590 000). The disease reproduction rate was calculated at 1.0336. All estimates refer to the 2015-2016 period. Conclusions: The estimated prevalence of CCD, especially among women of childbearing age, highlights the challenge of vertical transmission in Brazilian municipalities. Mathematical projections suggest that these estimates should be included in the national program for the elimination of vertical transmission of Chagas disease.
Objetivo: El objetivo de este estudio fue estimar la prevalencia de la enfermedad de Chagas crónica en la población brasileña en general, en las mujeres y en las mujeres en edad fértil. Métodos: Se realizó un metanálisis de la bibliografía para extraer datos sobre la prevalencia de la enfermedad de Chagas crónica en la población brasileña en general, en las mujeres y en las mujeres en edad fértil, en los municipios de Brasil durante el período 2010-2022. Se seleccionaron los indicadores relacionados con esa enfermedad disponibles en los sistemas municipales de información de salud. La modelización estadística de los datos extraídos del metanálisis, en función de los obtenidos de los sistemas de información, se aplicó a modelos lineales, lineales generalizados y aditivos. Resultados: Se seleccionaron los cinco modelos más apropiados de un total de 549 modelos evaluados, para obtener un modelo de consenso (R2 ajustado = 54%). El factor predictor más importante fue el registro de la enfermedad de Chagas crónica autodeclarada en el sistema de información de atención primaria de salud. De los 5570 municipios brasileños, en 1792 (32%) la prevalencia estimada fue nula y en los 3778 restantes la prevalencia media fue del 3,25% (± 2,9%). El número estimado de pacientes con enfermedad de Chagas crónica en la población brasileña en general, en las mujeres y en las mujeres en edad fértil fue de ~3,7 millones, ~2,1 millones y ~590 000, respectivamente. La tasa calculada de reproducción de la enfermedad fue de 1,0336. Todas las estimaciones se refieren al período 2015-2016. Conclusiones: La prevalencia estimada de la enfermedad de Chagas crónica, especialmente en las mujeres en edad fértil, pone de manifiesto el desafío que representa la transmisión vertical en los municipios brasileños. Estas estimaciones están en línea con los patrones de las proyecciones matemáticas, y sugieren la necesidad de incorporarlas al Pacto Nacional para la Eliminación de la Transmisión Vertical de la Enfermedad de Chagas.
RESUMO
[RESUMO]. Objetivo. Este estudo teve como objetivo estimar a prevalência da doença de Chagas (DC) crônica (DCC) na população brasileira, em mulheres e em mulheres em idade fértil. Métodos. Foi realizada uma metanálise da literatura para extrair dados de prevalência de DCC na população brasileira, em mulheres e em mulheres em idade fértil, em municípios do Brasil, no período 2010–2022. Indi- cadores relacionados com a DCC disponíveis nos sistemas de informação em saúde foram selecionados em escala municipal. A modelagem estatística dos dados extraídos da metanálise em função daqueles obtidos dos sistemas de informação foi aplicada a modelos lineares, lineares generalizados e aditivos. Resultados. Foram selecionados os cinco modelos mais adequados de um total de 549 modelos testados para obtenção de um modelo de consenso (R2 ajustado = 54%). O preditor mais importante foi o cadastro autorreferido de DCC do sistema de informação da Atenção Primária à Saúde. Dos 5 570 munícipios brasi- leiros, a prevalência foi estimada como zero em 1 792 (32%); nos 3 778 municípios restantes, a prevalência média da doença foi estimada em 3,25% (± 2,9%). O número de portadores de DCC foi estimado na popu- lação brasileira (~3,7 milhões), mulheres (~2,1 milhões) e mulheres em idade fértil (~590 mil). A taxa de reprodução da doença foi calculada em 1,0336. Todas as estimativas se referem ao intervalo 2015–2016. Conclusões. As prevalências estimadas de DCC, especialmente entre mulheres em idade fértil, evidenciam o desafio da transmissão vertical em municípios brasileiros. Estas estimativas são comparadas aos padrões de projeções matemáticas, sugerindo sua incorporação ao Pacto Nacional para a Eliminação da Transmissão Vertical da DC.
[ABSTRACT]. Objective. The objective of this study is to estimate the prevalence of chronic Chagas disease (CCD) in Brazil: in the general population, in women, and in women of childbearing age. Methods. A meta-analysis of the literature was conducted to extract data on the prevalence of CCD in munici- palities in Brazil in the 2010–2022 period: in the general population, in women, and in women of childbearing age. Municipal-level CCD indicators available in health information systems were selected. Statistical mode- ling of the data extracted from the meta-analysis (based on data obtained from information systems) was applied to linear, generalized linear, and additive models. Results. The five most appropriate models were selected from a total of 549 models tested to obtain a con- sensus model (adjusted R2 = 54%). The most important predictor was self-reported CCD in the primary health care information system. Zero prevalence was estimated in 1 792 (32%) of Brazil’s 5 570 municipalities; in the remaining 3 778 municipalities, average prevalence of the disease was estimated at 3.25% (± 2.9%). The number of carriers of CCD was estimated for the Brazilian population (~3.7 million), for women (~2.1 million) and for women of childbearing age (~590 000). The disease reproduction rate was calculated at 1.0336. All estimates refer to the 2015–2016 period. Conclusions. The estimated prevalence of CCD, especially among women of childbearing age, highlights the challenge of vertical transmission in Brazilian municipalities. Mathematical projections suggest that these estimates should be included in the national program for the elimination of vertical transmission of Chagas disease.
[RESUMEN]. Objetivo. El objetivo de este estudio fue estimar la prevalencia de la enfermedad de Chagas crónica en la población brasileña en general, en las mujeres y en las mujeres en edad fértil. Métodos. Se realizó un metanálisis de la bibliografía para extraer datos sobre la prevalencia de la enfermedad de Chagas crónica en la población brasileña en general, en las mujeres y en las mujeres en edad fértil, en los municipios de Brasil durante el período 2010-2022. Se seleccionaron los indicadores relacionados con esa enfermedad disponibles en los sistemas municipales de información de salud. La modelización estadística de los datos extraídos del metanálisis, en función de los obtenidos de los sistemas de información, se aplicó a modelos lineales, lineales generalizados y aditivos. Resultados. Se seleccionaron los cinco modelos más apropiados de un total de 549 modelos evaluados, para obtener un modelo de consenso (R2 ajustado = 54%). El factor predictor más importante fue el registro de la enfermedad de Chagas crónica autodeclarada en el sistema de información de atención primaria de salud. De los 5570 municipios brasileños, en 1792 (32%) la prevalencia estimada fue nula y en los 3778 restantes la prevalencia media fue del 3,25% (± 2,9%). El número estimado de pacientes con enfermedad de Chagas crónica en la población brasileña en general, en las mujeres y en las mujeres en edad fértil fue de ~3,7 millo- nes, ~2,1 millones y ~590 000, respectivamente. La tasa calculada de reproducción de la enfermedad fue de 1,0336. Todas las estimaciones se refieren al período 2015-2016. Conclusiones. La prevalencia estimada de la enfermedad de Chagas crónica, especialmente en las mujeres en edad fértil, pone de manifiesto el desafío que representa la transmisión vertical en los municipios brasi- leños. Estas estimaciones están en línea con los patrones de las proyecciones matemáticas, y sugieren la necesidad de incorporarlas al Pacto Nacional para la Eliminación de la Transmisión Vertical de la Enfermedad de Chagas.
Assuntos
Doença de Chagas , Modelos Estatísticos , Prevalência , Revisão Sistemática , Doença de Chagas , Modelos Estatísticos , Prevalência , Revisão Sistemática , Doença de Chagas , Modelos Estatísticos , Prevalência , Revisão SistemáticaRESUMO
We aimed to validate the CMPS-SF according to COSMIN and GRADE guidelines. Four trained evaluators assessed 208 videos (pre-operative-M1, peak of pain-M2, 1 h after the peak of pain and analgesia (rescue)-M3, and 24 h post-extubation-M4) of 52 dogs, divided into negative controls (n = 10), soft tissue surgeries (n = 22), and orthopedic surgeries (n = 20). The videos were randomized and blinded as to when they were filmed, and were evaluated in two stages, 21 days apart. According to confirmatory analysis, the CMPS-SF is a unidimensional scale. Intra-observer reliability was between 0.80 and 0.99 and inter-observer reliability between 0.73 and 0.86. Criterion validity was confirmed by the correlation between the CMPS-SF and other unidimensional scales (≥0.7). The differences between the scores were M2 ≥ M3 > M4 > M1 (responsiveness), and the scale presented construct validity (higher postoperative pain scores in dogs undergoing surgery versus control). Internal consistency was 0.7 (Cronbach's α) and 0.77 (McDonald's ω), and the item-total correlation was between 0.3 and 0.7, except for "A(ii)-Attention to wound". Specificity and sensitivity were 78-87% and 74-83%, respectively. The cut-off point for rescue analgesia was ≥5 or ≥4 excluding item B(iii) mobility, and the GRADE classification was high, confirming the validity of the scale.
RESUMO
BACKGROUND In Brazil, Leishmania (Leishmania) infantum is a widely distributed protozoan parasite. The human leishmaniasis caused by this species is often associated with visceral form. Tegumentary leishmaniasis (TL) cases due to L. (L.) infantum in the country are considered rare but may be underestimated. Although probably uncommon, these cases represent a new challenge to the prevention and control of leishmaniasis. OBJECTIVES Here, we describe two distinct cases of TL with atypical clinical presentations caused by L. (L.) infantum. METHODS AND FINDINGS Parasites were isolated from cutaneous lesions of the two patients and typed as L. (L.) infantum after sequencing of the ribosomal DNA internal transcribed spacer. The dermotropic L. (L.) infantum isolates were compared in terms of growth culture patterns, metacyclogenesis and in vitro infectivity in macrophages. MAIN CONCLUSIONS This study addresses the emergence of L. (L.) infantum as a causative agent of cutaneous disease in a visceral leishmaniasis hotspot located in northeast Brazil. The data presented provides novel information about the presence of dermotropic L. (L.) infantum in the country and demonstrates the infectivity potential of theses isolates.
RESUMO
Resumo Objetivo. Este estudo teve como objetivo estimar a prevalência da doença de Chagas (DC) crônica (DCC) na população brasileira, em mulheres e em mulheres em idade fértil. Métodos. Foi realizada uma metanálise da literatura para extrair dados de prevalência de DCC na população brasileira, em mulheres e em mulheres em idade fértil, em municípios do Brasil, no período 2010-2022. Indicadores relacionados com a DCC disponíveis nos sistemas de informação em saúde foram selecionados em escala municipal. A modelagem estatística dos dados extraídos da metanálise em função daqueles obtidos dos sistemas de informação foi aplicada a modelos lineares, lineares generalizados e aditivos. Resultados. Foram selecionados os cinco modelos mais adequados de um total de 549 modelos testados para obtenção de um modelo de consenso (R2 ajustado = 54%). O preditor mais importante foi o cadastro autorreferido de DCC do sistema de informação da Atenção Primária à Saúde. Dos 5 570 munícipios brasileiros, a prevalência foi estimada como zero em 1 792 (32%); nos 3 778 municípios restantes, a prevalência média da doença foi estimada em 3,25% (± 2,9%). O número de portadores de DCC foi estimado na população brasileira (~3,7 milhões), mulheres (~2,1 milhões) e mulheres em idade fértil (~590 mil). A taxa de reprodução da doença foi calculada em 1,0336. Todas as estimativas se referem ao intervalo 2015-2016. Conclusões. As prevalências estimadas de DCC, especialmente entre mulheres em idade fértil, evidenciam o desafio da transmissão vertical em municípios brasileiros. Estas estimativas são comparadas aos padrões de projeções matemáticas, sugerindo sua incorporação ao Pacto Nacional para a Eliminação da Transmissão Vertical da DC.
ABSTRACT Objective. The objective of this study is to estimate the prevalence of chronic Chagas disease (CCD) in Brazil: in the general population, in women, and in women of childbearing age. Methods. A meta-analysis of the literature was conducted to extract data on the prevalence of CCD in municipalities in Brazil in the 2010-2022 period: in the general population, in women, and in women of childbearing age. Municipal-level CCD indicators available in health information systems were selected. Statistical modeling of the data extracted from the meta-analysis (based on data obtained from information systems) was applied to linear, generalized linear, and additive models. Results. The five most appropriate models were selected from a total of 549 models tested to obtain a consensus model (adjusted R2 = 54%). The most important predictor was self-reported CCD in the primary health care information system. Zero prevalence was estimated in 1 792 (32%) of Brazil's 5 570 municipalities; in the remaining 3 778 municipalities, average prevalence of the disease was estimated at 3.25% (± 2.9%). The number of carriers of CCD was estimated for the Brazilian population (~3.7 million), for women (~2.1 million) and for women of childbearing age (~590 000). The disease reproduction rate was calculated at 1.0336. All estimates refer to the 2015-2016 period. Conclusions. The estimated prevalence of CCD, especially among women of childbearing age, highlights the challenge of vertical transmission in Brazilian municipalities. Mathematical projections suggest that these estimates should be included in the national program for the elimination of vertical transmission of Chagas disease.
Resumen Objetivo. El objetivo de este estudio fue estimar la prevalencia de la enfermedad de Chagas crónica en la población brasileña en general, en las mujeres y en las mujeres en edad fértil. Métodos. Se realizó un metanálisis de la bibliografía para extraer datos sobre la prevalencia de la enfermedad de Chagas crónica en la población brasileña en general, en las mujeres y en las mujeres en edad fértil, en los municipios de Brasil durante el período 2010-2022. Se seleccionaron los indicadores relacionados con esa enfermedad disponibles en los sistemas municipales de información de salud. La modelización estadística de los datos extraídos del metanálisis, en función de los obtenidos de los sistemas de información, se aplicó a modelos lineales, lineales generalizados y aditivos. Resultados. Se seleccionaron los cinco modelos más apropiados de un total de 549 modelos evaluados, para obtener un modelo de consenso (R2 ajustado = 54%). El factor predictor más importante fue el registro de la enfermedad de Chagas crónica autodeclarada en el sistema de información de atención primaria de salud. De los 5570 municipios brasileños, en 1792 (32%) la prevalencia estimada fue nula y en los 3778 restantes la prevalencia media fue del 3,25% (± 2,9%). El número estimado de pacientes con enfermedad de Chagas crónica en la población brasileña en general, en las mujeres y en las mujeres en edad fértil fue de ~3,7 millones, ~2,1 millones y ~590 000, respectivamente. La tasa calculada de reproducción de la enfermedad fue de 1,0336. Todas las estimaciones se refieren al período 2015-2016. Conclusiones. La prevalencia estimada de la enfermedad de Chagas crónica, especialmente en las mujeres en edad fértil, pone de manifiesto el desafío que representa la transmisión vertical en los municipios brasileños. Estas estimaciones están en línea con los patrones de las proyecciones matemáticas, y sugieren la necesidad de incorporarlas al Pacto Nacional para la Eliminación de la Transmisión Vertical de la Enfermedad de Chagas.
RESUMO
The early diagnosis of leprosy serves as an important tool to reduce the incidence of this disease in the world. Phage display (PD) technology can be used for mapping new antigens to the development of immunodiagnostic platforms. Our objective was to identify peptides that mimic Mycobacterium leprae proteins as serological markers using phage display technology. The phages were obtained in the biopanning using negative and positive serum from household contacts and leprosy patients, respectively. Then, the peptides were synthesized and validated in silico and in vitro for detection of IgG from patients and contacts. To characterize the native protein of M. leprae, scFv antibodies were selected against the synthetic peptides by PD. The scFv binding protein was obtained by immunocapture and confirmed using mass spectrometry. We selected two phase-fused peptides, MPML12 and MPML14, which mimic the HSP60 protein from M. leprae. The peptides MPML12 and MPML14 obtained 100% and 92.85% positivity in lepromatous patients. MPML12 and MPM14 detect IgG, especially in the multibacillary forms. The MPML12 and MPML14 peptides had positivity of 11.1% and 16.6% in household contacts, respectively. There was no cross-reaction in patient's samples with visceral leishmaniasis, tuberculosis and other mycobacteriosis for both peptides. Given these results and the easy obtainment of mimetic antigens, our peptides are promising markers for application in the diagnosis of leprosy, especially in endemic and hyperendemic regions.
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Leishmaniasis is a disease caused by protozoa of the genus Leishmania. Treatment options are limited, and there are frequent cases of treatment failure and clinical relapse. To understand these phenomena better, a systematic review was conducted, considering studies published between 1990 and 2021 in Portuguese, English, and Spanish. The review included 64 articles divided into three categories. Case reports (26 articles) focused on treatment failure and clinical relapse in cutaneous leishmaniasis patients (47.6%), primarily affecting males (74%) and children (67%), regardless of the clinical manifestation. Experimental studies on the parasite (19 articles), particularly with L. major (25%), indicated that alterations in DNA and genic expression (44.82%) played a significant role in treatment failure and clinical relapse. Population data on the human host (19 articles) identified immunological characteristics as the most associated factor (36%) with treatment failure and clinical relapse. Each clinical manifestation of the disease presented specificities in these phenomena, suggesting a multifactorial nature. Additionally, the parasites were found to adapt to the drugs used in treatment. In summary, the systematic review revealed that treatment failure and clinical relapse in leishmaniasis are complex processes influenced by various factors, including host immunology and parasite adaptation.