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1.
Parasite Immunol ; : e12797, 2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32984951

RESUMO

BACKGROUND: Early biomarkers of the response to treatment are lacking and may help to reduce mortality by the vector-borne disease visceral leishmaniasis (VL). METHODS: A prospective cohort study was conducted to investigate plasma cytokines and clinical laboratory data as biomarkers of the early response to specific treatment for VL in 36 patients. RESULTS: The mean interleukin 6 (IL-6) concentration on the 7th day was 2.3% of the pre-treatment concentration, interleukin 10 (IL-10) was 8.0%, and interleukin 8 (IL-8) was 8.2%. On the 7th day, IL-10 was below half of the pre-treatment concentration in 100.0%, IL-8 in 95.5% and IL-6 in 90.9%. The spleen and liver sizes, haemoglobin, interleukin 1 beta (IL-1ß) and tumour necrosis factor alpha (TNF-α) showed a slower recovery. Fever disappeared in 91% on the 7th day, 69.4% had a normal white cell count, and 77.8% had a normal platelet value by this time. CONCLUSIONS: The plasma cytokines IL-6, IL-10 and IL-8 were demonstrated to be excellent markers of the early response to VL treatment and if tested before the 7th day, will likely prove to be better than fever measurement.

2.
Sci Rep ; 10(1): 12321, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32704096

RESUMO

Visceral leishmaniasis (VL) is a life-threatening disease caused by the protozoa Leishmania donovani and L. infantum. Likely, L. infantum was introduced in the New World by the Iberic colonizers. Due to recent introduction, the genetic diversity is low. Access to genomic information through the sequencing of Leishmania isolates allows the characterization of populations through the identification and analysis of variations. Population structure information may reveal important data on disease dynamics. Aiming to describe the genetic diversity of L. infantum from the Middle-North, Brazil, next generation sequencing of 30 Leishmania isolates obtained in the city of Teresina, from where the disease dispersed, was performed. The variations were categorized accordingly to the genome region and impact and provided the basis for chromosomal ploidy and population structure analysis. The results showed low diversity between the isolates and the Iberic reference genome JPCM5. Most variations were seen in non-coding regions, with modifying impact. The ploidy number analysis showed aneuploid profile. The population structure analysis revealed the presence of two L. infantum populations identified in Teresina. Further population genetics studies with a larger number of isolates should be performed in order to identify the genetic background associated with virulence and parasite ecology.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32491143

RESUMO

In Latin America, the causative agent of kala-azar is the intracellular protozoan Leishmania infantum. Most cases in South America are reported in Brazil. Worldwide, it mainly affects Bangladesh, Ethiopia, India, South Sudan and Sudan. Despite the high morbidity and lethality of kala-azar, most infections are asymptomatic. However, a small portion of patients evolves with recurrence of kala-azar becoming symptomatic even after all available drug treatments. Kala-azar is not a formal indication for splenectomy in adults. Splenectomy is recommended as a saving measure, when kala-azar is associated with symptomatic hypersplenism and for drug-resistant cases. In the study, we report two cases of kala-azar with splenomegaly that presented several hospitalizations due to the recurrence of the kala-azar, in addition to hospitalizations for normalizing the blood count. After splenectomy, kala-azar cases and the effects of hypersplenism are cured. Thus, splenectomy should be seen as a surgical treatment option with a curative purpose in patients with recurrent kala-azar, in whom the possibilities of drug therapy have been exhausted and even so they progressed with hypersplenism and clinical repercussions.


Assuntos
Leishmaniose Visceral/cirurgia , Adulto , Humanos , Masculino , Recidiva , Esplenectomia , Resultado do Tratamento
4.
Rev Soc Bras Med Trop ; 53: e20190446, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130324

RESUMO

INTRODUCTION: Visceral leishmaniasis (VL) represents a public health concern in several areas of the world. In the American continent, VL transmission is typically zoonotic, but humans with active VL caused by Leishmania infantum are able to infect sandflies. Thus, individuals with cutaneous parasitic infections may act as reservoirs and allow interhuman transmission. Additionally, the skin may be responsible for reactivation of the disease after therapy. This study's objective was to evaluate cutaneous parasitism in humans with VL in an American endemic area. METHODS: A cross-sectional hospital-based study was conducted in northeast Brazil from October 2016 to April 2017. Biopsies of healthy skin for histopathology and immunohistochemistry were performed prior to treatment in all study patients. RESULTS: Twenty-two patients between the ages of five months to 78 years were included in the study. Seven patients (31.8%) tested positive for HIV. Only one patient had cutaneous parasitism, as confirmed by immunohistochemistry prior to treatment. Parasitism was not detected after treatment. CONCLUSIONS: Cutaneous parasitism in the healthy skin of humans with visceral leishmaniasis, although unusual, may be a source of infection for phlebotomine sandflies.


Assuntos
Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/parasitologia , Pele/parasitologia , Adolescente , Adulto , Idoso , Biópsia , Criança , Pré-Escolar , Estudos Transversais , Escolaridade , Doenças Endêmicas , Feminino , Humanos , Imuno-Histoquímica , Lactente , Leishmaniose Visceral/patologia , Masculino , Pessoa de Meia-Idade , Pele/patologia , Adulto Jovem
5.
Rev. Soc. Bras. Med. Trop ; 53: e20190446, 2020. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1092226

RESUMO

Abstract INTRODUCTION: Visceral leishmaniasis (VL) represents a public health concern in several areas of the world. In the American continent, VL transmission is typically zoonotic, but humans with active VL caused by Leishmania infantum are able to infect sandflies. Thus, individuals with cutaneous parasitic infections may act as reservoirs and allow interhuman transmission. Additionally, the skin may be responsible for reactivation of the disease after therapy. This study's objective was to evaluate cutaneous parasitism in humans with VL in an American endemic area. METHODS: A cross-sectional hospital-based study was conducted in northeast Brazil from October 2016 to April 2017. Biopsies of healthy skin for histopathology and immunohistochemistry were performed prior to treatment in all study patients. RESULTS: Twenty-two patients between the ages of five months to 78 years were included in the study. Seven patients (31.8%) tested positive for HIV. Only one patient had cutaneous parasitism, as confirmed by immunohistochemistry prior to treatment. Parasitism was not detected after treatment. CONCLUSIONS: Cutaneous parasitism in the healthy skin of humans with visceral leishmaniasis, although unusual, may be a source of infection for phlebotomine sandflies.

6.
Nutr. hosp ; 36(5): 1205-1212, sept.-oct. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-184646

RESUMO

Introduction: much evidence confirms that vitamin D may be associated with an improvement in CD4 cell counts in HIV-infected individuals, where antiretroviral therapy (ART) is used and associated with decreased 25(OH)D levels. Objective: to carry out a systematic review on the effect of vitamin D supplementation on HIV-infected adult patients. Methods: the research was conducted in the databases Science Direct, PubMed, BVS, Scielo Cochrane and Periods, from February to April 2018, with publication limit from 2000 to 2018, without restriction of gender, ethnicity and involving individuals with age older than 18 years. To evaluate the quality of the studies, we used the protocol Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) and the Jadad scale. Results: the search initially resulted in 198 articles. After the selection process 5 articles were identified as eligible, where they highlight that vitamin D supplementation may be an associated and effective intervention to reduce hypovitaminosis. ART reduces vitamin D3 levels and changes its metabolism, being associated with the risk of mortality. However, adequate levels of 25(OH)D are positively associated with the number of CD4 + cells and the reduction of infection levels. Conclusion: vitamin D supplementation promotes immune recovery. However, the cases analysed were few, insufficient to fully confirm the benefits and recommend supplementation. Therefore, intervention studies are needed to elucidate the role of vitamin D in human protection against HIV infections


Introducción: muchas evidencias ratifican que la vitamina D puede estar asociada con la mejora de los niveles de células CD4 en individuos infectados por el VIH, tratados con terapia antirretroviral (ART) que se asocia a la disminución de los niveles de 25(OH)D. Objetivo: realizar una revisión sistemática sobre el efecto de la suplementación de vitamina D en pacientes adultos infectados con VIH. Métodos: la investigación fue realizada en las bases de datos Science Direct, PubMed, BVS, Scielo Cochrane y periódicos, de febrero a abril de 2018, con límite de publicación de 2000 a 2018, sin restricción de género, etnicidad y que involucra a individuos con edad mayores de 18 años. Para la evaluación de la calidad de los estudios, se utilizó el protocolo Preferred Reporting Items for Systematic Reviews y Meta-Analyzes (PRISMA) y la escala de Jadad. Resultados: la encuesta inicialmente resultó en 198 artículos. Después del proceso de selección, 5 artículos fueron identificados como elegibles, donde ponen de manifiesto que la suplementación con vitamina D puede ser una intervención asociada y eficaz para reducir la hipovitaminosis. La ART reduce niveles de la vitamina D3 y altera su metabolismo, estando asociada al riesgo de mortalidad. Sin embargo, los niveles adecuados de 25(OH)D están asociados positivamente al número de células CD4 + y la reducción de los niveles de infecciones. Conclusión: la suplementación de vitamina D promueve la recuperación inmunológica. Sin embargo, los casos analizados fueron pocos, insuficientes para confirmar totalmente los beneficios y recomendar la suplementación. Por lo tanto, estudios de intervención son necesarios para elucidar la actuación de la vitamina D en la protección humana contra las infecciones por el VIH


Assuntos
Humanos , Colecalciferol/administração & dosagem , Colecalciferol/metabolismo , Infecções por HIV/dietoterapia , Infecções por HIV/imunologia , Linfócitos T CD4-Positivos/imunologia , Reconstituição Imune
7.
Nutr Hosp ; 36(5): 1205-1212, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31526009

RESUMO

Introduction: Introduction: much evidence confirms that vitamin D may be associated with an improvement in CD4 cell counts in HIV-infected individuals, where antiretroviral therapy (ART) is used and associated with decreased 25(OH)D levels. Objective: to carry out a systematic review on the effect of vitamin D supplementation on HIV-infected adult patients. Methods: the research was conducted in the databases Science Direct, PubMed, BVS, Scielo Cochrane and Periods, from February to April 2018, with publication limit from 2000 to 2018, without restriction of gender, ethnicity and involving individuals with age older than 18 years. To evaluate the quality of the studies, we used the protocol Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) and the Jadad scale. Results: the search initially resulted in 198 articles. After the selection process 5 articles were identified as eligible, where they highlight that vitamin D supplementation may be an associated and effective intervention to reduce hypovitaminosis. ART reduces vitamin D3 levels and changes its metabolism, being associated with the risk of mortality. However, adequate levels of 25(OH)D are positively associated with the number of CD4 + cells and the reduction of infection levels. Conclusion: vitamin D supplementation promotes immune recovery. However, the cases analysed were few, insufficient to fully confirm the benefits and recommend supplementation. Therefore, intervention studies are needed to elucidate the role of vitamin D in human protection against HIV infections.


Assuntos
Colecalciferol/uso terapêutico , Suplementos Nutricionais , Infecções por HIV/tratamento farmacológico , Adulto , Humanos
8.
Am J Trop Med Hyg ; 101(4): 789-794, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31436148

RESUMO

In India, visceral leishmaniasis (VL) caused by Leishmania donovani has been successfully treated with miltefosine with a cure rate of > 90%. To assess the efficacy and safety of oral miltefosine against Brazilian VL, which is caused by Leishmania infantum, a phase II, open-label, dose-escalation study of oral miltefosine was conducted in children (aged 2-12 years) and adolescent-adults (aged 13-60 years). Definitive cure was assessed at a 6-month follow-up visit. The cure rate was only 42% (6 of 14 patients) with a recommended treatment of 28 days and 68% (19 of 28 patients) with an extended treatment of 42 days. The in vitro miltefosine susceptibility profile of intracellular amastigote stages of the pretreatment isolates, from cured and relapsed patients, showed a positive correlation with the clinical outcome. The IC50 mean (SEM) of eventual cures was 5.1 (0.4) µM, whereas that of eventual failures was 12.8 (1.9) µM (P = 0.0002). An IC50 above 8.0 µM predicts failure with 82% sensitivity and 100% specificity. The finding of L. infantum amastigotes resistant to miltefosine in isolates from patients who eventually failed treatment strongly suggests natural resistance to this drug, as miltefosine had never been used in Brazil before this trial was carried out.


Assuntos
Antiprotozoários/administração & dosagem , Leishmania infantum/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Fosforilcolina/análogos & derivados , Adolescente , Adulto , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Imunidade Inata , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/parasitologia , Masculino , Pessoa de Meia-Idade , Fosforilcolina/administração & dosagem , Falha de Tratamento , Adulto Jovem
9.
Epidemiol Serv Saude ; 27(3): e2017329, 2018 10 22.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30365697

RESUMO

OBJECTIVE: to describe a simplified protocol to diagnose suspected cases of meningitis. METHODS: this is an experience report on the approach to diagnosing meningitis at the Tropical Diseases Reference Service in the state of Piauí, Brazil, between 2007 and 2016; information was extracted from the Notifiable Diseases Information System (SINAN) and the laboratory record book; the chi-square test was used to compare epidemiological surveillance indicators based on final meningitis case classification; the Phi coefficient was used to verify the correlation between presumed diagnosis and laboratory-confirmed diagnosis. RESULTS: considering the 4,096 cases of meningitis investigated, there was a reduction in the generic classification of meningitis cases from 72% to 47% (p<0.001); indicated laboratory investigation profile showed agreement with final meningitis case diagnosis. (rf=0.66; p<0.001). CONCLUSION: a greater proportion of specific etiologic diagnosis of meningitis was achieved while the protocol was in use.


Assuntos
Sistemas de Informação , Meningite/diagnóstico , Vigilância da População , Brasil/epidemiologia , Técnicas de Laboratório Clínico , Humanos , Meningite/classificação , Meningite/epidemiologia
10.
Am J Trop Med Hyg ; 98(1): 126-133, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29141704

RESUMO

Visceral leishmaniasis (VL) caused by Leishmania infantum is a lethal disease transmitted by sand flies. Although, considered a zoonosis with dogs held as the main reservoirs, humans are also sources of infection. Therefore, control policies currently focused on dog culling may need to consider that VL and human immunodeficiency virus (HIV)/VL patients may also be infectious, contributing to transmission. Reservoir competence of patients with VL without and with HIV infection and of persons asymptomatically infected with Leishmania was assessed by xenodiagnosis with the vector Lutzomyia longipalpis. Parasites in sand fly's guts were identified by using optical microscopy and by conventional polymerase chain reaction (PCR). Leishmania infantum blood parasite burden was determined by quantitative PCR. Among the 61 participants, 27 (44%) infected sand flies as seen by microscopy or PCR. When infectiousness was assessed by microscopy, xenodiagnosis was positive in five (25%) patients not infected with HIV, whereas nine (45%) of those harboring HIV were positive. Among the 19 asymptomatic patients four (21%) infected sand flies only demonstrated by PCR. One (50%) asymptomatic patient with HIV had a positive xenodiagnosis by microscopy. 9/372 (2.4%) and 37/398 (9.2%) sand flies were infected when feeding in patients without and with HIV, respectively. Infectiousness was poorly correlated with quantitative PCR. The study shows that asymptomatic humans are capable of transmitting L. infantum, that ill persons with HIV infection are more infectious to sand flies, and that humans are more important reservoirs than previously thought. This fact may be considered when designing control policies for zoonotic VL.


Assuntos
Reservatórios de Doenças/parasitologia , Infecções por HIV/psicologia , Leishmania infantum , Leishmaniose Visceral/transmissão , Psychodidae/parasitologia , Adolescente , Adulto , Idoso , Animais , Criança , Pré-Escolar , Coinfecção/parasitologia , Coinfecção/virologia , Reservatórios de Doenças/virologia , Feminino , Infecções por HIV/complicações , Humanos , Lactente , Leishmaniose Visceral/complicações , Leishmaniose Visceral/parasitologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
Parasitol Res ; 117(2): 419-427, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29270768

RESUMO

Because of visceral leishmaniasis (VL) urbanization and spreading of the human immunodeficiency virus (HIV) infection to rural areas, coinfection has become more common. Here, we compared the accuracy of Kalazar Detect® (KD), an rK39-based immunochromatographic (IC) test, and OrangeLife® (OL), an rK39 + rK28 IC test, for diagnosing VL in patients coinfected with HIV in an endemic area in Brazil. Seventy-six VL patients and 40 patients with other diseases, of which 31 and 21 patients, respectively, were infected with HIV, were examined. The sensitivity of OL and KD tests was 88.89 and 95.45%, respectively, in patients without HIV. The sensitivity dropped to 67.74 and 61.29%, respectively, in coinfected patients. The decrease in sensitivity was not related to a decrease in the production of Leishmania-specific IgG. Because of the low sensitivity of rk39 test in HIV-infected patients, we suggest that patients with negative rK39 results should undergo further investigation with additional serological tests that are not based only on the rK39 antigen and examination of bone marrow aspirates.


Assuntos
Cromatografia de Afinidade/métodos , Infecções por HIV/complicações , Leishmaniose Visceral/diagnóstico , Adulto , Antígenos de Protozoários/imunologia , Brasil , Coinfecção , Feminino , Humanos , Leishmaniose Visceral/complicações , Masculino , Proteínas de Protozoários/imunologia , Sensibilidade e Especificidade
12.
Epidemiol. serv. saúde ; 27(3): e2017329, 2018. tab, graf
Artigo em Português | LILACS | ID: biblio-975175

RESUMO

Objetivo: descrever um protocolo simplificado para abordagem de casos suspeitos de meningite. Métodos: relato de experiência na abordagem diagnóstica das meningites no serviço de referência em doenças tropicais do estado do Piauí, Brasil, no período de 2007-2016; extraíram-se informações do Sistema de Informação de Agravos de Notificação (Sinan) e do livro de registro do laboratório; utilizou-se o teste do qui-quadrado para comparar os indicadores da vigilância epidemiológica baseados na classificação final dos casos de meningite; utilizou-se o teste de concordância Phi para verificar a correlação entre os diagnósticos etiológicos presumidos pelo protocolo e aqueles confirmados laboratorialmente. Resultados: considerando-se 4.096 casos de meningite estudados, houve redução na classificação genérica desses casos, de 72 para 47% (p<0,001); a indicação do perfil de investigação laboratorial mostrou concordância com o diagnóstico final dos casos de meningite (rf=0,66; p<0,001). Conclusão: o diagnóstico etiológico específico das meningites foi alcançado em maior proporção durante a utilização do protocolo.


Objetivo: describir un protocolo para el abordaje de casos sospechosos de meningitis. Métodos: se relata la experiencia del diagnóstico de meningitis en el servicio de referencia para enfermedades tropicales del estado de Piauí, Brasil, entre 2007 y 2016; extrajimos informaciones del Sistema de Información de Notificación (Sinan) y del libro de laboratorio; la prueba de chi-cuadrado verificó la alteración de los indicadores de la vigilancia epidemiológica basados en la clasificación de los casos de meningitis; usamos la prueba de concordancia Phi para correlacionar los diagnósticos etiológicos presumidos por el protocolo y aquellos confirmados laboratorialmente. Resultados: considerando los 4.096 casos de meningitis investigados, se observó reducción en la clasificación genérica de casos del 72 al 47% (p<0,001); la selección del perfil de investigación mostró concordancia con la clasificación final de los casos de meningitis (rf=0,66; p<0,001). Conclusión: el diagnóstico etiológico de las meningitis se alcanzó en mayor proporción durante la utilización del protocolo.


Objective: to describe a simplified protocol to diagnose suspected cases of meningitis. Methods: this is an experience report on the approach to diagnosing meningitis at the Tropical Diseases Reference Service in the state of Piauí, Brazil, between 2007 and 2016; information was extracted from the Notifiable Diseases Information System (SINAN) and the laboratory record book; the chi-square test was used to compare epidemiological surveillance indicators based on final meningitis case classification; the Phi coefficient was used to verify the correlation between presumed diagnosis and laboratory-confirmed diagnosis. Results: considering the 4,096 cases of meningitis investigated, there was a reduction in the generic classification of meningitis cases from 72% to 47% (p<0.001); indicated laboratory investigation profile showed agreement with final meningitis case diagnosis. (rf=0.66; p<0.001). Conclusion: a greater proportion of specific etiologic diagnosis of meningitis was achieved while the protocol was in use.


Assuntos
Humanos , Masculino , Feminino , Líquido Cefalorraquidiano , Monitoramento Epidemiológico , Meningite/diagnóstico , Epidemiologia Descritiva
13.
Rev Soc Bras Med Trop ; 50(4): 483-488, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28954069

RESUMO

INTRODUCTION: The control of reservoirs for Leishmania infantum -induced zoonotic visceral leishmaniasis requires the identification of dogs posing a population risk. Here, we assessed the performance of several assays to identify Lutzomyia longipalpis infectious dogs. METHODS: We evaluated 99 dogs that were positive for visceral leishmaniasis based on parasite identification. Serological analyses were performed using an enzyme-linked immunosorbent assay, immunofluorescence antibody tests in 1:40 and 1:80 dilutions, rapid dual path platform tests, immunochromatographic assay with a recombinant rK39 antigen, fast agglutination screening tests, and direct agglutination tests. We also performed PCR to analyze peripheral blood and xenodiagnosis. RESULTS: Forty-six dogs infected at least one L. longipalpis specimen. Although the serological test sensitivities were above 85% for detecting L. longipalpis infectious dogs, none showed a satisfactory performance, as both specificity (0.06 to 13%) and the area under the receiver operating characteristic curve (45 to 53%) were low. The PCR results were also weak, with a sensitivity of 30%, specificity of 72%, and an area under the receiver operating characteristic curve of 51%. The infected L. longipalpis proportion was higher among asymptomatic dogs than symptomatic dogs. Among the symptomatic dogs, those with ulceration-free skin diseases were more infectious, with an odds ratio of 9.3 (confidence interval of 1.10 - 428.5). The larger the number of insects fed, the greater the detected infectiousness. CONCLUSIONS: Our study supports the imperative to develop novel technologies for identifying the infectious dogs that transmit L. infantum for the benefit of public health.


Assuntos
Anticorpos Antiprotozoários/sangue , Doenças do Cão/diagnóstico , Leishmania infantum , Leishmaniose Visceral/veterinária , Mosquitos Vetores/parasitologia , Psychodidae/parasitologia , Testes Sorológicos/veterinária , Animais , Doenças do Cão/parasitologia , Doenças do Cão/transmissão , Cães , Feminino , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/transmissão , Masculino , Sensibilidade e Especificidade , Testes Sorológicos/métodos
14.
Rev. Soc. Bras. Med. Trop ; 50(4): 483-488, July-Aug. 2017. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-896987

RESUMO

Abstract INTRODUCTION The control of reservoirs for Leishmania infantum -induced zoonotic visceral leishmaniasis requires the identification of dogs posing a population risk. Here, we assessed the performance of several assays to identify Lutzomyia longipalpis infectious dogs. METHODS We evaluated 99 dogs that were positive for visceral leishmaniasis based on parasite identification. Serological analyses were performed using an enzyme-linked immunosorbent assay, immunofluorescence antibody tests in 1:40 and 1:80 dilutions, rapid dual path platform tests, immunochromatographic assay with a recombinant rK39 antigen, fast agglutination screening tests, and direct agglutination tests. We also performed PCR to analyze peripheral blood and xenodiagnosis. RESULTS Forty-six dogs infected at least one L. longipalpis specimen. Although the serological test sensitivities were above 85% for detecting L. longipalpis infectious dogs, none showed a satisfactory performance, as both specificity (0.06 to 13%) and the area under the receiver operating characteristic curve (45 to 53%) were low. The PCR results were also weak, with a sensitivity of 30%, specificity of 72%, and an area under the receiver operating characteristic curve of 51%. The infected L. longipalpis proportion was higher among asymptomatic dogs than symptomatic dogs. Among the symptomatic dogs, those with ulceration-free skin diseases were more infectious, with an odds ratio of 9.3 (confidence interval of 1.10 - 428.5). The larger the number of insects fed, the greater the detected infectiousness. CONCLUSIONS Our study supports the imperative to develop novel technologies for identifying the infectious dogs that transmit L. infantum for the benefit of public health.

15.
Rev Inst Med Trop Sao Paulo ; 59: e39, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28591267

RESUMO

Dogs are considered the main reservoir of Leishmania infantum. This protozoan causes visceral leishmaniasis (VL), an uncontrolled urban zoonosis in Brazil. Serological tests and polymerase chain reaction (PCR) on peripheral blood were performed to identify infected dogs in scenarios of higher and lower prevalence of the disease (Teresina and Vitória). One-hundred infected and 57 non-infected animals from Teresina and 100 non-infected animals from Vitória were studied. Animal selection was not dependent on previous serology. The sensitivity (Teresina) and specificity (Teresina and Vitória) were as follows: indirect antibody fluorescence (IFAT) cut-off of 1:40 (IFAT 1:40): 96%, 18%, and 76%; IFAT 1:80: 90%, 33%, and 93%; direct agglutination test (DAT): 96%, 33%, and 98%; fast agglutination screening test (FAST): 93%, 68%, and 100%; immunochromatographic assay with a recombinant rK39 antigen (rK39): 88%, 74%, and 98%; enzyme linked immunosorbent assay (ELISA): 91%, 79%, and 98%; rapid dual-path platform test (TR DPP®): 98%, 60%, and 98%; and blood PCR: 29%, 93%, and 97%, respectively. In the high transmission area, none of the tests adequately discriminated L. infantum-infected from non-infected dogs. However, in the high transmission city, the area under the receiver operating characteristic (ROC) curve of FAST, DAT, ICrK39, ELISA and TR DPP® was high.


Assuntos
Anticorpos Antiprotozoários/sangue , Doenças do Cão/diagnóstico , Técnicas Imunológicas/métodos , Leishmania infantum/imunologia , Leishmaniose Visceral/veterinária , Animais , Brasil/epidemiologia , Doenças do Cão/epidemiologia , Doenças do Cão/parasitologia , Cães , Feminino , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/epidemiologia , Masculino , Programas de Rastreamento , Prevalência , Sensibilidade e Especificidade
16.
PLoS Negl Trop Dis ; 11(6): e0005706, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28662034

RESUMO

BACKGROUND: There is insufficient evidence to support visceral leishmaniasis (VL) treatment recommendations in Brazil and an urgent need to improve current treatments. Drug combinations may be an option. METHODS: A multicenter, randomized, open label, controlled trial was conducted in five sites in Brazil to evaluate efficacy and safety of (i) amphotericin B deoxycholate (AmphoB) (1 mg/kg/day for 14 days), (ii) liposomal amphotericin B (LAMB) (3 mg/kg/day for 7 days) and (iii) a combination of LAMB (10 mg/kg single dose) plus meglumine antimoniate (MA) (20 mg Sb+5/kg/day for 10 days), compared to (iv) standard treatment with MA (20 mg Sb+5/kg/day for 20 days). Patients, aged 6 months to 50 years, with confirmed VL and without HIV infection were enrolled in the study. Primary efficacy endpoint was clinical cure at 6 months. A planned efficacy and safety interim analysis led to trial interruption. RESULTS: 378 patients were randomized to the four treatment arms: MA (n = 112), AmphoB (n = 45), LAMB (n = 109), or LAMB plus MA (n = 112). A high toxicity of AmphoB prompted an unplanned interim safety analysis and this treatment arm was dropped. Per intention-to-treat protocol final analyses of the remaining 332 patients show cure rates at 6 months of 77.5% for MA, 87.2% for LAMB, and 83.9% for LAMB plus MA, without statistically significant differences between the experimental arms and comparator (LAMB: 9.7%; CI95% -0.28 to 19.68, p = 0.06; LAMB plus MA: 6.4%; CI95% -3.93 to 16.73; p = 0.222). LAMB monotherapy was safer than MA regarding frequency of treatment-related adverse events (AE) (p = 0.045), proportion of patients presenting at least one severe AE (p = 0.029), and the proportion of AEs resulting in definitive treatment discontinuation (p = 0.003). CONCLUSIONS: Due to lower toxicity and acceptable efficacy, LAMB would be a more suitable first line treatment for VL than standard treatment. ClinicalTrials.gov identification number: NCT01310738. TRIAL REGISTRATION: ClinicalTrials.gov NCT01310738.


Assuntos
Anfotericina B/uso terapêutico , Antiprotozoários/uso terapêutico , Leishmaniose Visceral/tratamento farmacológico , Meglumina/uso terapêutico , Compostos Organometálicos/uso terapêutico , Adolescente , Adulto , Anfotericina B/efeitos adversos , Antiprotozoários/efeitos adversos , Brasil , Criança , Pré-Escolar , Quimioterapia Combinada/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Lactente , Masculino , Meglumina/efeitos adversos , Antimoniato de Meglumina , Pessoa de Meia-Idade , Compostos Organometálicos/efeitos adversos , Resultado do Tratamento , Adulto Jovem
19.
Rev. Inst. Med. Trop. Säo Paulo ; 59: e39, 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-842782

RESUMO

ABSTRACT Dogs are considered the main reservoir of Leishmania infantum. This protozoan causes visceral leishmaniasis (VL), an uncontrolled urban zoonosis in Brazil. Serological tests and polymerase chain reaction (PCR) on peripheral blood were performed to identify infected dogs in scenarios of higher and lower prevalence of the disease (Teresina and Vitória). One-hundred infected and 57 non-infected animals from Teresina and 100 non-infected animals from Vitória were studied. Animal selection was not dependent on previous serology. The sensitivity (Teresina) and specificity (Teresina and Vitória) were as follows: indirect antibody fluorescence (IFAT) cut-off of 1:40 (IFAT 1:40): 96%, 18%, and 76%; IFAT 1:80: 90%, 33%, and 93%; direct agglutination test (DAT): 96%, 33%, and 98%; fast agglutination screening test (FAST): 93%, 68%, and 100%; immunochromatographic assay with a recombinant rK39 antigen (rK39): 88%, 74%, and 98%; enzyme linked immunosorbent assay (ELISA): 91%, 79%, and 98%; rapid dual-path platform test (TR DPP®): 98%, 60%, and 98%; and blood PCR: 29%, 93%, and 97%, respectively. In the high transmission area, none of the tests adequately discriminated L. infantum-infected from non-infected dogs. However, in the high transmission city, the area under the receiver operating characteristic (ROC) curve of FAST, DAT, ICrK39, ELISA and TR DPP® was high.


Assuntos
Animais , Masculino , Feminino , Cães , Anticorpos Antiprotozoários/sangue , Doenças do Cão/diagnóstico , Técnicas Imunológicas/métodos , Leishmania infantum/imunologia , Leishmaniose Visceral/veterinária , Brasil/epidemiologia , Doenças do Cão/epidemiologia , Doenças do Cão/parasitologia , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/epidemiologia , Programas de Rastreamento , Prevalência , Sensibilidade e Especificidade
20.
Rev Soc Bras Med Trop ; 49(6): 728-740, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28001220

RESUMO

INTRODUCTION: Early identification of patients at higher risk of progressing to severe disease and death is crucial for implementing therapeutic and preventive measures; this could reduce the morbidity and mortality from kala-azar. We describe a score set composed of four scales in addition to software for quick assessment of the probability of death from kala-azar at the point of care. METHODS:: Data from 883 patients diagnosed between September 2005 and August 2008 were used to derive the score set, and data from 1,031 patients diagnosed between September 2008 and November 2013 were used to validate the models. Stepwise logistic regression analyses were used to derive the optimal multivariate prediction models. Model performance was assessed by its discriminatory accuracy. A computational specialist system (Kala-Cal(r)) was developed to speed up the calculation of the probability of death based on clinical scores. RESULTS:: The clinical prediction score showed high discrimination (area under the curve [AUC] 0.90) for distinguishing death from survival for children ≤2 years old. Performance improved after adding laboratory variables (AUC 0.93). The clinical score showed equivalent discrimination (AUC 0.89) for older children and adults, which also improved after including laboratory data (AUC 0.92). The score set also showed a high, although lower, discrimination when applied to the validation cohort. CONCLUSIONS:: This score set and Kala-Cal(r) software may help identify individuals with the greatest probability of death. The associated software may speed up the calculation of the probability of death based on clinical scores and assist physicians in decision-making.


Assuntos
Leishmaniose Visceral/mortalidade , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Software , Adulto Jovem
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