Prediction of visceral leishmaniasis incidence using the Seasonal Autoregressive Integrated Moving Average model (SARIMA) in the state of Maranhão, Brazil / Previsão da incidência da leishmaniose visceral usando o modelo de média móvel integrado autorregressivo sazonal (SARIMA) no Maranhão, Brasil

Abstract Visceral leishmaniasis (VL) is an infectious disease predominant in countries located in the tropics. The prediction of occurrence of infectious diseases through epidemiologic modeling has revealed to be an important tool in the understanding of its occurrence dynamic. The objective of this study was to develop a forecasting model for the incidence of VL in Maranhão using the Seasonal Autoregressive Integrated Moving Average model (SARIMA). We collected monthly data regarding VL cases from the National Disease Notification System (SINAN) corresponding to the period between 2001 and 2018. The Box-Jenkins method was applied in order to adjust a SARIMA prediction model for VL general incidence and by sex (male or female) for the period between January 2019 and December 2013. For 216 months of this time series, 10,431 cases of VL were notified in Maranhão, with an average of 579 cases per year. With regard to age range, there was a higher incidence among the pediatric public (0 to 14 years of age). There was a predominance in male cases, 6437 (61.71%). The Box-Pierce test figures for overall, male and female genders supported by the results of the Ljung-Box test suggest that the autocorrelations of residual values act as white noise. Regarding monthly occurrences in general and by gender, the SARIMA models (2,0,0) (2,0,0), (0,1,1) (0,1,1) and (0,1,1) (2, 0, 0) were the ones that mostly adjusted to the data respectively. The model SARIMA has proven to be an adequate tool for predicting and analyzing the trends in VL incidence in Maranhão. The time variation determination and its prediction are decisive in providing guidance in health measure intervention.

Resumo A leishmaniose visceral (LV) é uma doença de natureza infecciosa, predominante em países de zonas tropicais. A predição de ocorrência de doenças infecciosas através da modelagem epidemiológica tem se revelado uma importante ferramenta no entendimento de sua dinâmica de ocorrência. O objetivo deste estudo foi desenvolver um modelo de previsão da incidência da LV no Maranhão usando o modelo de Média Móvel Integrada Autocorrelacionada Sazonal (SARIMA). Foram coletados os dados mensais de casos de LV através do Sistema de Informação de Agravos de Notificação (SINAN) correspondentes ao período de 2001 a 2018. O método de Box-Jenkins foi aplicado para ajustar um modelo de predição SARIMA para incidência geral e por sexo (masculino e feminino) de LV para o período de janeiro de 2019 a dezembro de 2023. Durante o período de 216 meses dessa série temporal, foram registrados 10.431 casos de LV no Maranhão, com uma média de 579 casos por ano. Em relação à faixa etária, houve maior registro no público pediátrico (0 a 14 anos). Houve predominância do sexo masculino, com 6437 casos (61,71%). Os valores do teste de Box-Pierce para incidência geral, sexo masculino e feminino reforçados pelos resultados do teste Ljung-Box sugerem que as autocorrelações de resíduos apresentam um comportamento de ruído branco. Para incidência mensal geral e por sexo masculino e feminino, os modelos SARIMA (2,0,0) (2,0,0), (0,1,1) (0,1,1) e (0,1,1) (2, 0, 0) foram os que mais se ajustaram aos dados, respectivamente. O modelo SARIMA se mostrou uma ferramenta adequada de previsão e análise da tendência de incidência da LV no Maranhão. A determinação da variação temporal e sua predição são determinantes no norteamento de medidas de intervenção em saúde.

Spatio-temporal analysis of the visceral leishmaniasis in the state of Alagoas, Brazil / Análise espacial-temporal da leishmaniose visceral no estado de Alagoas

Visceral leishmaniosis is a neglected tropical disease. We evaluated the spatial distribution of cases of visceral leishmaniosis in the state of Alagoas, Brazil. All cases of VL, registered by the health department, were analyzed and georeferenced. Results: Between 2008 and 2017, 97.1% of the municipalities presented sporadic classification of transmission. With temporal evolution, the incidence of cases of visceral leishmaniosis was concentrated in most municipalities in the microregion of Santana do Ipanema-AL. Space-time analysis, if considered, may promote the improvement of surveillance and control actions of visceral leishmaniosis.

A leishmaniose visceral é uma doença tropical negligenciada. Foram avaliadas a distribuição espacial dos casos de leishmaniose visceral no estado de Alagoas. Todos os casos de LV, registrados pela secretaria de saúde, foram analisados e georreferenciados. Entre 2008 e 2017, 97,1% dos municípios apresentaram classificação esporádica de transmissão. Com a evolução temporal, a incidência de casos de leishmaniose visceral se concentrou na maioria dos municípios da microrregião de Santana do Ipanema-AL. A análise espaço-tempo, se considerada, pode promover o aprimoramento das ações de vigilância e controle da leishmaniose visceral.

Prediction of visceral leishmaniasis incidence using the Seasonal Autoregressive Integrated Moving Average model (SARIMA) in the state of Maranhão, Brazil

Abstract Visceral leishmaniasis (VL) is an infectious disease predominant in countries located in the tropics. The prediction of occurrence of infectious diseases through epidemiologic modeling has revealed to be an important tool in the understanding of its occurrence dynamic. The objective of this study was to develop a forecasting model for the incidence of VL in Maranhão using the Seasonal Autoregressive Integrated Moving Average model (SARIMA). We collected monthly data regarding VL cases from the National Disease Notification System (SINAN) corresponding to the period between 2001 and 2018. The Box-Jenkins method was applied in order to adjust a SARIMA prediction model for VL general incidence and by sex (male or female) for the period between January 2019 and December 2013. For 216 months of this time series, 10,431 cases of VL were notified in Maranhão, with an average of 579 cases per year. With regard to age range, there was a higher incidence among the pediatric public (0 to 14 years of age). There was a predominance in male cases, 6437 (61.71%). The Box-Pierce test figures for overall, male and female genders supported by the results of the Ljung-Box test suggest that the autocorrelations of residual values act as white noise. Regarding monthly occurrences in general and by gender, the SARIMA models (2,0,0) (2,0,0), (0,1,1) (0,1,1) and (0,1,1) (2, 0, 0) were the ones that mostly adjusted to the data respectively. The model SARIMA has proven to be an adequate tool for predicting and analyzing the trends in VL incidence in Maranhão. The time variation determination and its prediction are decisive in providing guidance in health measure intervention.

Resumo A leishmaniose visceral (LV) é uma doença de natureza infecciosa, predominante em países de zonas tropicais. A predição de ocorrência de doenças infecciosas através da modelagem epidemiológica tem se revelado uma importante ferramenta no entendimento de sua dinâmica de ocorrência. O objetivo deste estudo foi desenvolver um modelo de previsão da incidência da LV no Maranhão usando o modelo de Média Móvel Integrada Autocorrelacionada Sazonal (SARIMA). Foram coletados os dados mensais de casos de LV através do Sistema de Informação de Agravos de Notificação (SINAN) correspondentes ao período de 2001 a 2018. O método de Box-Jenkins foi aplicado para ajustar um modelo de predição SARIMA para incidência geral e por sexo (masculino e feminino) de LV para o período de janeiro de 2019 a dezembro de 2023. Durante o período de 216 meses dessa série temporal, foram registrados 10.431 casos de LV no Maranhão, com uma média de 579 casos por ano. Em relação à faixa etária, houve maior registro no público pediátrico (0 a 14 anos). Houve predominância do sexo masculino, com 6437 casos (61,71%). Os valores do teste de Box-Pierce para incidência geral, sexo masculino e feminino reforçados pelos resultados do teste Ljung-Box sugerem que as autocorrelações de resíduos apresentam um comportamento de ruído branco. Para incidência mensal geral e por sexo masculino e feminino, os modelos SARIMA (2,0,0) (2,0,0), (0,1,1) (0,1,1) e (0,1,1) (2, 0, 0) foram os que mais se ajustaram aos dados, respectivamente. O modelo SARIMA se mostrou uma ferramenta adequada de previsão e análise da tendência de incidência da LV no Maranhão. A determinação da variação temporal e sua predição são determinantes no norteamento de medidas de intervenção em saúde.

Spatio-temporal analysis of the visceral leishmaniasis in the state of Alagoas, Brazil

Abstract Visceral leishmaniosis is a neglected tropical disease. We evaluated the spatial distribution of cases of visceral leishmaniosis in the state of Alagoas, Brazil. All cases of VL, registered by the health department, were analyzed and georeferenced. Results: Between 2008 and 2017, 97.1% of the municipalities presented sporadic classification of transmission. With temporal evolution, the incidence of cases of visceral leishmaniosis was concentrated in most municipalities in the microregion of Santana do Ipanema-AL. Space-time analysis, if considered, may promote the improvement of surveillance and control actions of visceral leishmaniosis.

Resumo A leishmaniose visceral é uma doença tropical negligenciada. Foram avaliadas a distribuição espacial dos casos de leishmaniose visceral no estado de Alagoas. Todos os casos de LV, registrados pela secretaria de saúde, foram analisados e georreferenciados. Entre 2008 e 2017, 97,1% dos municípios apresentaram classificação esporádica de transmissão. Com a evolução temporal, a incidência de casos de leishmaniose visceral se concentrou na maioria dos municípios da microrregião de Santana do Ipanema-AL. A análise espaço-tempo, se considerada, pode promover o aprimoramento das ações de vigilância e controle da leishmaniose visceral.

Leishmaniose Visceral Humana: monitoramento epidemiológico e indicadores de vida nos municípios da Bahia, Brasil / Human Visceral Leishmaniasis: epidemiological monitoring and life indicators in the municipalities of Bahia, Brazil

O comportamento dos indicadores de vida dos casos notificados de Leishmaniose Visceral (LV) na Bahia e fatores sociodemográficos foram analisados. Trata-se de um estudo analítico e retrospectivo (2010 a 2020) que utilizou dados secundários do SINAN/DATASUS. Foram analisados dados de notificações, incidência, transmissão, estratificação de risco e indicadores de vida. No período foram registrados 3.573 casos de LV, maior incidência de 3,52 casos/100 mil habitantes e transmissão esporádica na maioria dos municípios. A Taxa de Incremento Anual (TIA) no Núcleo Regional de Saúde Sul e Leste apresentou valores significativos para a incidência e, para a letalidade, na Oeste, Leste e Centro-Norte. O Disability Adjusted Life Years (DALY) demonstrou que a população baiana infectada perdeu 10 anos de vida. A análise de aspectos individuais dos municípios permitiu identificar a necessidade de implementação de políticas públicas efetivas nessa esfera administrativa.

The behavior of life indicators of notified cases of Visceral Leishmaniasis (VL) in Bahia and sociodemographic factors were analyzed. The study analyzes the behavior of life indicators of notified cases of Visceral Leishmaniasis (VL) in Bahia and its correlation with sociodemographic factors. This is an analytical and retrospective study (2010 - 2020) that used the SINAN/DATASUS secondary database between. Were analyzed data on notifications, incidence, transmission, risk stratification and life indicators. During the period there were 3,573 cases of VL, highest incidence of 3.52 cases/100,000 inhabitants and sporadic transmission in most municipalities. The Annual Increment Rate (AIR) in the South and East health macro-regions showed significant values for incidence and lethality in the West, East and Center-North regions. Disability Adjusted Life Years (DALY) showed that the infected Bahian population lost 10 years of life. The analysis of individual aspects of the municipalities made it possible to identify the need to implement effective public policies at this administrative level.

Temporal trend in the incidence of human visceral leishmaniasis in Brazil / Tendência temporal da incidência de leishmaniose visceral humana no Brasil

Abstract It is an ecological study that analyzed the time trend of visceral leishmaniasis incidence rates in Brazil using segmented time regression by joinpoints. There was a decreasing incidence rate of this disease in the country with an average annual percent change (AAPC) of -5 (CI95%: -9.1; -0.6) and a reduction of 1.69 cases/100 thousand inhabitants in 2007, and 0.91/100 thousand inhabitants in 2020. The Central-West region showed the highest reduction percent (AAPC: -9.1; CI95%: -13.8; -4.3), followed by the Southeast region (AAPC: -8.7; -14.6; -2.5). The North and South regions showed the largest number of joinpoints in the time series. The highest incidences were recorded in the male population, however, stable (AAPC: 2.14; CI95%: -8.3; 0). In the age group analysis, the trend was decreasing for the groups from 0 to 4 years old (AAPC: -7.7; CI95%: -12.6; -2.4), 5 to 9 years old (AAPC: -7.3; CI95%: -13.6; -0,4) and 10 to 14 years old (AAPC: -5.5; CI95%: -10.3; -0.3). It was found that although Visceral Leishmaniasis is an endemic disease in Brazil, there was a decrease in its incidence rate from 2007 to 2020.

Resumo Trata-se de um estudo ecológico que analisou a tendência temporal das taxas de incidência de leishmaniose visceral no Brasil mediante regressão temporal segmentada por pontos de inflexão. Observou-se tendência de decréscimo na taxa de incidência dessa patologia no país, com variação variação percentual média anual (average annual percent change - AAPC) de -5 (IC95%: -9,1; -0,6) e redução de 1,69 casos/100 mil habitantes em 2007, para 0,91/100 mil habitantes em 2020. A região Centro-Oeste apresentou a maior redução do AAPC (AAPC: -9,1; IC95%: -13,8; -4,3), seguida da região Sudeste (AAPC: -8,7; -14,6; -2,5). As regiões Norte e Sul apresentaram o maior número de pontos de inflexão (joinpoint) na série temporal. As maiores incidências foram registradas na população masculina, porém com tendência estacionária (AAPC: 2,14; IC95%: -8,3; 0). Na análise por faixa etária, a tendência foi decrescente nos grupos de 0 a 4 anos (AAPC: -7,7; IC95%: -12,6; -2,4), 5 a 9 anos (AAPC: -7,3; IC95%: -13,6; -0,4) e de 10 a 14 anos (AAPC: -5,5; IC95%: -10,3; -0,3). Verificou-se que, apesar de a leishmaniose visceral se tratar de uma doença endêmica no Brasil, houve declínio na sua taxa de incidência no período de 2007 a 2020.

Perfil epidemiológico das notificações de leishmaniose no estado de Pernambuco no Brasil de 2015-2019 / Epidemiological profile of leishmaniasis notifications in the Pernambuco state in Brazil from 2015-2019

Aqui, fornecemos uma análise epidemiológica da leishmaniose em Pernambuco, Brasil, de 2015 a 2019. Nossos resultados revelaram 1.705 casos de leishmaniose tegumentar americana-LTA e 859 casos de leishmaniose visceral-LV. LV e LTA afetam crianças de 1 a 4 anos (23% e 3,2% dos casos, respectivamente) e adultos de 20 a 39 anos (26% e 28%, respectivamente), principalmente mulheres. O maior percentual (54,6%) de casos de LV foi encontrado na área urbana, enquanto LTA ocorreu principalmente na área rural (63,2%). Indivíduos com maior escolaridade foram menos acometidos pela leishmaniose e dados de prognóstico revelaram boas chances de cura clínica, mas óbitos ainda são registrados. Esses dados mostram que ações preventivas de saúde devem ser desenvolvidas para impedir a disseminação da leishmaniose, reduzir seu impacto na saúde pública e restaurar a qualidade de vida da população. Este estudo pode ser útil na elaboração de estratégias para minimizar os impactos da leishmaniose.

Here, we provide an epidemiological analysis of leishmaniasis in Pernambuco, Brazil, from 2015 to 2019. Our results revealed 1,705 of American cutaneous leishmaniasis-ACL and 859 cases of visceral leishmaniasis-VL. VL and ACL affect children aged 1­4 years (23% and 3.2% of all cases, respectively) and adults aged 20­39 years (26% and 28%, respectively), mainly women. The highest percentage (54.6%) of VL cases was found in urban areas, while ACL occurred mainly in rural areas (63.2%). Individuals with a higher level of education were less affected by leishmaniasis and data on prognosis revealed good chances of clinical cure, but deaths are still recorded. These data show that preventive health actions must be developed to hinder leishmaniasis spread, reduce its impact on public health, and restore the population's life quality. This study can be useful in further elaboration of strategies to minimize leishmaniasis impacts.

Seleção de antígenos de Leishmania infantum por imunoproteômica para emprego no diagnóstico da leishmaniose visceral humana / Selection of Leishmania infantum antigens by immunoproteomics for use in the diagnosis of human visceral leishmaniasis

O controle da leishmaniose visceral (LV) requer um diagnóstico e tratamento adequados, uma vez que o diagnóstico preciso é fundamental para um regime medicamentoso eficaz para os pacientes. Nesse contexto, as ferramentas biotecnológicas devem ser aprimoradas para o manejo clínico e a avaliação epidemiológica da doença. No entanto, existem limitações relacionadas com a sensibilidade e/ou especificidade dos antígenos usados atualmente, mostrando a necessidade de identificação de novas moléculas para serem testadas em um diagnóstico sorológico mais sensível e específico. Neste sentido, no presente estudo, uma abordagem imunoproteômica foi usada para identificar proteínas antigênicas das formas promastigotas e amastigotas da espécie Leishmania infantum, causadora de LV em nosso país, por meio de seu reconhecimento por anticorpos em soros de pacientes com a doença. Amostras de indivíduos saudáveis residentes em região endêmica da doença e de pacientes com Doença de Chagas foram utilizadas com a função de se obter proteínas mais específicas ao parasito Leishmania para serem avaliadas no diagnóstico da LV. Como resultados obtidos, um total de 29 e 21 proteínas foram identificadas nos extratos de formas promastigotas e amastigotas dos parasitos, respectivamente. Para a validação da capacidade diagnóstica, duas proteínas, endonuclease III e GTP-binding protein, foram selecionadas, clonadas, expressas e purificadas para serem testadas em experimentos de ELISA. Os resultados dos testes mostraram valores de sensibilidade e especificidade superiores a 99,0% para a identificação da LV. Os antígenos ainda exibiram um diferencial ao apresentarem baixa reatividade sorológica em pacientes curados e tratados, sugerindo a possibilidade de que as mesmas possam ser aplicadas como marcadores prognósticos da doença. Em conclusão, o estudo imunoproteômico se mostrou eficaz na seleção de proteínas antigênicas de L. infantum e duas delas, endonuclease III e GTP-binding protein, foram bem avaliadas para o diagnóstico da LV frente a um painel sorológico, além de demonstrarem um potencial para monitoramento de pacientes com LV após o tratamento.

The control of visceral leishmaniasis (VL) requires an adequate diagnosis and treatment, since an accurate diagnosis is essential for an effective medication regimen for patients. In this context, biotechnological tools must be improved for the clinical management and epidemiological assessment of the disease. However, there are limitations related to the sensitivity and / or specificity of the antigens currently used, showing the necessity to identify new molecules to be tested in a more sensitive and specific serological diagnosis. In this sense, in the present study, an immunoproteomics approach was used to identify antigenic proteins of the Leishmania infantum promastigote and amastigote forms, which causes VL in our country, through its recognition by antibodies in sera of patients with the disease. Samples from healthy individuals living in an endemic region of the disease and from patients with Chagas disease were used to obtain more specific proteins for the Leishmania parasite, aiming their future application in the VL diagnosis. As results obtained, a total of 29 and 21 proteins were identified in the extracts of parasitic promastigotes and amastigotes, respectively. For validation of the diagnostic capacity, two proteins, endonuclease III and GTP-binding protein, were selected, cloned, expressed and purified to be tested in ELISA experiments. The test results showed sensitivity and specificity values greater than 99.0% for the identification of VL. The antigens also exhibited a differential when presenting low serological reactivity in cured and treated patients, suggesting the possibility that they can be applied as prognostic markers of the disease. In conclusion, the immunoproteomic study proved to be effective in the selection of L. infantum antigenic proteins and two of them, endonuclease III and GTP-binding protein, were well evaluated for the diagnosis of VL against a serological panel, in addition, demonstrating a potential for monitoring patients with VL after treatment.

Genetic variability of Leishmania (Leishmania) infantum causing human visceral leishmaniasis in the Southeastern Brazil

ABSTRACT Leishmania infantum is a protozoan that causes visceral leishmaniasis (VL) in the Americas and some regions of Europe. The disease is mainly characterized by hepatosplenomegaly and fever, and can be fatal. Factors related to the host and parasite can contribute to the transmission of Leishmania and the clinical outcome. The intraspecific genetic variability of L. infantum strains may be one of these factors. In this study, we evaluated the genetic variability of L. infantum obtained from bone marrow smear slides from patients in the Sao Paulo State, Brazil. For this, the minicircle of the kDNA hypervariable region was used as target by Sanger sequencing. By analyzing the similarity of the nucleotides and the maximum likelihood tree (Fasttree), we observed a high similarity (98%) among samples. Moreover, we identified four different profiles of L. infantum. In conclusion, L. infantum strains from Sao Paulo State, Brazil, showed low diversity measured by minicircle of the kDNA hypervariable region.

Visceral Leishmaniasis Revealing Undiagnosed Inborn Errors of Immunity

ABSTRACT Visceral Leishmaniasis (VL) is a potentially fatal disease and may be associated with primary or acquired immunodeficiencies. There are few reports, in the literature, of inborn errors of immunity. Here, we report two cases of VL as a marker of inborn errors of immunity, namely, GATA2 and RAB27A deficiency. Our data suggest that VL patients should be screened for primary immunodeficiency, particularly in cases of VL relapse.

Leishmaniasis visceral. Presentación de un caso y revisión de la entidade

La leishmania la describieron Leishman y Donovan en 1903, al aislar el parásito del bazo de las personas afectadas. La leishmaniasis es una enfermedad tropical y subtropical, causada por un protozoo intracelular del género Leishmania y transmitida a los humanos por la picadura de vectores Lutzomyias infectadas. Tiene como reservorios a los perros, roedores, lobos, zorros y el humano como huésped incidental. Clínicamente la leishmaniasis puede clasificarse en tres formas principales: leishmaniasis cutánea (LC), localizada (LCL) o difusa (LCD), leishmaniasis destructiva mucocutánea (LMC) y leishmaniasis visceral (LV o Kala-Azar). La enfermedad se manifiesta clínicamente con la invasión del parásito y daño en funcionamiento de órganos vitales como son la médula ósea, el hígado y el bazo. Se presenta el caso de un paciente masculino adolescente de 11 anos de edad de zona rural que presenta un cuadro clínico de aumento de volumen de abdomen superior, palidez marcada, decaimento, con hepato y esplenomegalia atendido en Bahía, Brasil en 2018 con diagnóstico de leishmaniasis. Se describe la clínica, médios diagnósticos y tratamiento.

Leishmania was described by Leishman and Donovan in 1903, when the parasite was isolated from the spleen of affected people. Leishmaniasis is a tropical and subtropical disease, caused by an intracellular protozoan of the genus Leishmania and transmitted to humans by the bite of infected Lutzomyia vectors. It has as reservoirs dogs, rodents, wolves, foxes and humans as incidental hosts. Clinically, leishmaniasis can be classified into three main forms: cutaneous (LC), localized (LCL) or diffuse (LCD) leishmaniasis, mucocutaneous destructive leishmaniasis (CML), and visceral leishmaniasis (VL or Kala-Azar). The disease manifests clinically with the invasion of the parasite and damage to the functioning of vital organs such as the bone marrow, liver and spleen.We present the case of an 11-year-old adolescent male patient from rural areas who presented a clinical picture of increased volume of the upper abdomen, marked pallor, decay, with hepato and splenomegaly treated in Bahia, Brazil in 2018 with a diagnosis of leishmaniasis. The clinic, diagnostic methods and treatment are described.

A leishmania foi descrita por Leishman e Donovan em 1903, quando o parasita foi isolado do baço das pessoas afetadas. A leishmaniose é uma doença tropical e subtropical, causada por um protozoário intracelular do gênero Leishmania e transmitida aos seres humanos pela picada de vetores de Lutzomyia infectados. Tem como reservatórios cães, roedores, lobos, raposas e humanos como hospedeiros incidentais. Clinicamente, a leishmaniose pode ser classificada em três formas principais: leishmaniose cutânea (LCL), localizada (LCL) ou difusa (LCD), leishmaniose mucocutânea destrutiva (LMC) e leishmaniose visceral (LV ou Kala-Azar). A doença se manifesta clinicamente com a invasão do parasita e danos ao funcionamento de órgãos vitais, como a medula óssea, fígado e baço.Apresentamos o caso de um adolescente de 11 anos, do sexo masculino, de áreas rurais, que apresentou quadro clínico de aumento do volume do abdome superior, palidez acentuada, cárie, com hepato e esplenomegalia tratado na Bahia, Brasil, em 2018, com diagnóstico de leishmaniose. A clínica, os métodos de diagnóstico e o tratamento são descritos.

What else in times of COVID-19? The role of minimally invasive autopsy for the differential diagnosis of acute respiratory failure in a case of kala-azar

ABSTRACT Visceral leishmaniasis (VL) is a chronic vector-borne zoonotic disease caused by trypanosomatids, considered endemic in 98 countries, mainly associated with poverty. About 50,000-90,000 cases of VL occur annually worldwide, and Brazil has the second largest number of cases in the world. The clinical picture of VL is fever, hepatosplenomegaly, and pancytopenia, progressing to death in 90% of cases due to secondary infections and multi-organ failure, if left untreated. We describe the case of a 25-year-old female who lived in the metropolitan area of Sao Paulo, who had recently taken touristic trips to several rural areas in Southeastern Brazil and was diagnosed post-mortem. During the hospitalization in a hospital reference for the treatment of COVID-19, the patient developed acute respiratory failure, with chest radiographic changes, and died due to refractory shock. The ultrasound-guided minimally invasive autopsy diagnosed VL (macrophages containing amastigote forms of Leishmania in the spleen, liver and bone marrow), as well as pneumonia and bloodstream infection by gram-negative bacilli.

Protease inhibitors as a potential agent against visceral Leishmaniasis: A review to inspire future study

Abstract Leishmaniasis is transmitted by sandfly which carries the intracellular protozoa in their midgut. Among visceral, cutaneous and mucocutaneous leishmaniasis, visceral type that is caused by Leishmania donovani is the most lethal one. Findings of leishmanial structure and species took place in 19th century and was initiated by Donovan. Leishmaniasis is still a major concern of health issues in many endemic countries in Asia, Africa, the Americas, and the Mediterranean region. Worldwide1.5-2 million new cases of cutaneous leishmaniasis and 500,000 cases of visceral leishmaniasis are reported each year. Leishmaniasis is endemic in nearly 90 countries worldwide and close to 12 million new cases of leishmaniasis are reported worldwide annually. Studies on antileishmanial drug development is of major concern as leishmaniasis are the second largest parasitic killer in the world and the available drugs are either toxic or costly. The major surface GP63 protease, also known as Zinc- metalloproteases present on the surface of leishmanial promastigotes, can be targeted for drug development. Protease inhibitors targeting such surface proteases show promising results. Different protease inhibitors have been isolated from marine actinobacteria against many infectious diseases. Metabolites produced by these actinobacteria may have greater importance for the discovery and development of new antileishmanial drugs. Hence, this review discusses the background, current situation, treatment, and protease inhibitors from marine actinobacteria for drug development against GP63 molecules.

Blood parasite load by qPCR as therapeutic monitoring in visceral leishmaniasis patients in Brazil: a case series study

ABSTRACT Background: This study aimed to describe the kinetics of Leishmania parasite load determined using kinetoplast DNA (kDNA)-based quantitative polymerase chain reaction (qPCR) in visceral leishmaniasis (VL) patients. Methods: Parasite load in blood was assessed by qPCR at five time points, up to 12 months post-diagnosis. Sixteen patients were followed up. Results: A significant reduction in the parasite load was observed after treatment (P < 0.0001). One patient had an increased parasite load 3 months post-treatment and relapsed clinically at month six. Conclusions: We have described the use of kDNA-based qPCR in the post-treatment follow-up of VL cases.

Análise temporal das notificações de leishmaniose visceral humana (LVH) da Microrregião de Pirapora-MG / Temporal analysis of notifications of human visceral leishmaniasis from the microregion of Pirapora ­ MG

Analisa o perfil epidemiológico da Leishmaniose Visceral Humana (LVH) nos municípios da microrregião de Pirapora. Métodos: Foram descritos e analisados, os dados epidemiológicos dos casos de LVH notificado na microrregião de Pirapora, no período de 2016 a 2020, avaliando tempo (número anual de casos por ano), (município) e dados das pessoas acometidas, tais como (sexo, idade, oportunidade de diagnóstico e de notificação do caso suspeito e caso final, estimativa de incidência e óbitos). Resultados: Foram notificados e confirmados 33 casos de LVH, distribuídos em seis municípios. Destes, 27 (81,82%) eram homens e 6 (18,18%) mulheres, a faixa etária mais prevalente foi de pessoas entre 40 - 59 anos, sendo os homens os mais acometidos. O maior número de registros positivos foi no ano de 2017 com uma incidência de 8 (15,15%) pessoas, caracterizando a região como área moderada de transmissão atingindo durante o período 2,7 casos/ano. Ocorreu 1 (3,03%) óbito durante todo o período, no ano de 2017 Conclusões: A microrregião de Pirapora caracteriza-se como área moderada para transmissão para Leishmaniose Visceral Humana. Medidas de prevenção e controle como o uso de inseticidas em massa, eliminação dos focos de reprodução do mosquito, uso de repelentes, telas nas janelas e programas de educação continuada nessas regiões devem ser incentivadas para evitar que novos indivíduos se infectem

To analyze the epidemiological profile of Human Visceral Leishmaniasis (LVH) in the municipalities of the micro-region of Pirapora. Methods: The epidemiological data of the cases of LVH notified in the micro-region of Pirapora, in the period from 2016 to 2020, were described and analyzed, evaluating time (annual number of cases per year), (municipality) and data of the affected people, such as (gender, age, timeliness of diagnosis and notification of the suspected and final case, estimated incidence and deaths). Results: 33 (100%) cases of LVH were notified and confirmed, distributed in six municipalities. Of these, 27 (81.82%) were men and 6 (18.185%) were women, the most prevalent age group was people between 40 - 59 years old, with men being the most affected. The highest number of positive records was in 2017 with an incidence of 8 (15.15%) people, characterizing the region as a moderate transmission area reaching 2.7 cases/year during the period. There was 1 (3.03%) death during the entire period, in 2017. Conclusions: The Pirapora microregion is characterized as a moderate area for transmission of Human Visceral Leishmaniasis. Prevention and control measures such as the mass use of insecticides, elimination of mosquito breeding sites, use of repellents, window screens and continuing education programs in these regions should be encouraged to prevent new individuals from becoming infected

The first imported case of visceral leishmaniasis in Shenzhen City / 中国血吸虫病防治杂志

A patient with fever, chills, and pancytopenia as major clinical manifestations was presented. To investigate the cause, the patient’s peripheral blood was collected for pathogen screening using metagenomic next - generation sequencing (mNGS). The DNA sequence of Leishmania donovani was detected, and Leishmania amastigotes were found in bone marrow smears using microscopy. The case was therefore definitively diagnosed as visceral leishmaniasis, and was cured and discharged from hospital following treatment with liposomal amphotericin B for 14 days. This is the first imported case of visceral leishmaniasis since the founding of Shenzhen City in 1979.

Visceral leishmaniasis in Xinjiang Uygur Autonomous Region during the COVID-19 pandemic: a case report / 中国血吸虫病防治杂志

Objective To perform an epidemiological investigation on a case of visceral leishmaniasis reported from Shule County, Kashi Prefecture, Xinjiang Uygur Autonomous Region in 2021, so as to provide insights into differential diagnosis of visceral leishmaniasis during the COVID-19 pandemic. Methods The epidemiological history of this case was collected, and the case was diagnosed for Leishmania infection with the immunochromatographic (rK39) strip test, bone marrow smear microscopy and PCR assay. Results The patient had typical clinical symptoms of leishmaniasis, including irregular fever, hepatosplenomeg- aly, low serum albumin and elevated globulin. Bone marrow smear microscopy identified L. donovani amastigotes, and both rK39 strip test and PCR assay were positive, while the case was tested negative for SARS-CoV-2. COVID-19 was therefore excluded and visceral leishmaniasis was diagnosed. Standard full-dose treatment with sodium stibogluconate was given, and no Leishmania was found on blood smears during the reexamination. No recurrence was found during the followup after discharge for hospital. Conclusions During the COVID-19 pandemic, it is recommended to increase the perception of differential diagnosis of visceral leishmaniasis among first-contact doctors, and reinforce the capability of differential diagnosis and health education of visceral leishmaniasis among medical and healthcare institutions at all levels, to prevent missed diagnosis and misdiagnosis of visceral leishmaniasis.

Serology for visceral leishmaniasis: How trusty is the accuracy reported by the manufacturers?

ABSTRACT Timely and accurate diagnosis is one of the strategies for managing visceral leishmaniasis (VL). Given the specificities of this infection, which affects different vulnerable populations, the local assessment of the accuracy of the available diagnostic test is a requirement for the good use of resources. In Brazil, performance data are required for test registration with the National Regulatory Agency (ANVISA), but there are no minimum requirements established for performance evaluation. Here, we compared the accuracy reported in the manufacturer's instructions of commercially available VL-diagnostic tests in Brazil, and the accuracies reported in the scientific literature which were obtained after test commercialization. The tests were identified via the electronic database of ANVISA, and their accuracy was obtained from the manufacturer's instructions. A literature search for test accuracy was performed using two databases. A total of 28 VL diagnostic tests were identified through the ANVISA database. However, only 13 presented performance data in the manufacturer's instructions, with five immunoenzymatic tests, three indirect immunofluorescence tests, one chemiluminescence test, and four rapid tests. For most tests, the manufacturers did not provide the relevant information, such as sample size, reference standards, and study site. The literature review identified accuracy data for only 61.5% of diagnostic tests registered in Brazil. These observations confirmed that there are significant flaws in the process of registering health technologies and highlighted one of the reasons for the insufficient control of policies, namely, the use of potentially inaccurate and inappropriate diagnostic tools for a given scenario.

Mapeando a leishmaniose visceral e tegumentar americana em Birigui-Sp: uma análise epidemiológica retrospectiva e geoespacial / Mapping american visceral and tegumentary leishmaniasis in Birigui-Sp: a retrospective and geospatial epidemiological analysis / Mapeo de la leishmaniasis visceral y tegumentaria americana en Birigui-Sp: un análisis epidemiológico retrospectivo y geoespacial

A leishmaniose é uma doença tropical infecciosa negligenciada com dois espectros clínicos, a Leishmaniose Visceral (LV) e a Leishmaniose Tegumentar Americana (LTA). O objetivo foi determinar a evolução epidemiológica e a distribuição espacial de LV e LTA em Birigui/SP, entre 2010 a 2020. Foi realizado um estudo retrospectivo e observacional, de LV e LTA registrados pelo Serviço de Vigilância Epidemiológica e os endereços foram utilizados para a análise espacial e distribuição dos casos dentro do município. Identificaram-se 233 casos de LV, com maior número em 2012 (15,45%) e 14 óbitos por LV (letalidade de 6,0%), com predomínio de indivíduos do sexo masculino (60,1%), brancos (71,7%), com idades entre 40 e 59 anos (28,8%), ensino médio completo (8,58%) e alta taxa de cura (65,7%) após tratamento. Verificou- se 25 casos de LTA sendo 2015 o ano com maior número de casos (22,2%) e com predomínio em homens (63%), maiores de 60 anos (44,4%), brancos (92,6%) e com ensino fundamental incompleto (18,5%). A manifestação clínica mais observada foi a forma cutânea (59,3%) com mais de 77% de cura após tratamento. Padrões significativos de agregação espacial foram detectados e áreas de cluster acumulam-se na região oriente do município de Birigui, com maior frequência em bairros mais periféricos. Conclui-se que, apesar de ser observada uma leve diminuição nos casos de LV e LTA, reforça-se a necessidade do monitoramento frequente, principalmente nas regiões com maior número de casos.

Leishmaniasis is a neglected tropical infectious disease with two clinical spectrums, Visceral Leishmaniasis (VL) and American Cutaneous Leishmaniasis (ACL). The objective was to determine the epidemiological evolution and spatial distribution of VL and ATL in Birigui/SP, between 2010 and 2020. spatial analysis and distribution of cases within the municipality. A total of 233 cases of VL were identified, with the highest number in 2012 (15.45%) and 14 deaths from VL (6.0% mortality), with a predominance of males (60.1%), whites (71.7%), aged between 40 and 59 years (28.8%), complete high school (8.58%) and high cure rate (65.7%) after treatment. There were 25 cases of ACL, with 2015 being the year with the highest number of cases (22.2%) and with a predominance of men (63%), over 60 years old (44.4%), white (92.6%) and with incomplete primary education (18.5%). The most observed clinical manifestation was the cutaneous form (59.3%) with more than 77% of cure after treatment. Significant patterns of spatial aggregation were detected, and cluster areas accumulated in the eastern region of the municipality of Birigui, with greater frequency in more peripheral neighborhoods. It is concluded that, despite a slight decrease in cases of VL and ATL, the need for frequent monitoring is reinforced, especially in regions with a higher number of cases.

La leishmaniasis es una enfermedad infecciosa tropical desatendida con dos espectros clínicos, la leishmaniasis visceral (LV) y la leishmaniasis cutánea americana (LCA). El objetivo fue determinar la evolución epidemiológica y distribución espacial de la LV y LCA en Birigui/SP, entre 2010 y 2020. análisis espacial y distribución de los casos dentro del municipio. Fueron identificados 233 casos de LV, con el mayor número en 2012 (15,45%) y 14 muertes por LV (6,0% de mortalidad), con predominio del sexo masculino (60,1%), raza blanca (71,7%), edad entre 40 y 59 años (28,8%), enseñanza media completa (8,58%) y alta tasa de cura (65,7%) después del tratamiento. Hubo 25 casos de LCA, siendo 2015 el año con mayor número de casos (22,2%) y con predominio de hombres (63%), mayores de 60 años (44,4%), blancos (92,6%) y con estudios primarios incompletos (18,5%). La manifestación clínica más observada fue la forma cutánea (59,3%) con más del 77% de curación tras el tratamiento. Se detectaron patrones significativos de agregación espacial, acumulándose áreas de conglomerados en la región este del municipio de Birigui, con mayor frecuencia en barrios más periféricos. Se concluye que, a pesar de una leve disminución de los casos de LV y ATL, se refuerza la necesidad de monitoreo frecuente, especialmente en las regiones con mayor número de casos.

Leishmaniose visceral: aspectos epidemiológicos, espaciais e temporais no município de Sobral, nordeste do Brasil, 2007-2019 / Visceral leishmaniasis: epidemiological, spatial and temporality aspects in the municipality of Sobral, northeast Brazil, 2007-2019

Objetivos: descrever os aspectos epidemiológicos, espaciais e temporais da leishmaniose visceral humana, no município de Sobral, no período de 2007 a 2019. Métodos: foi realizado um estudo epidemiológico descritivo e ecológico de análise espacial e temporal, com uso dos programas Quantum-Gis e Joinpoint. Resultados: foram confirmados 316 casos novos, predominantemente, no sexo masculino, nas faixas etárias de 1 a 4 anos (26,3%) e de 20 a 39 anos (24,0%), na zona urbana. Febre (95,9%), fraqueza (85,1%), emagrecimento (80,1%), palidez (73,7%), esplenomegalia (75,6%) e hepatomegalia (69,3%) foram os sinais clínicos mais frequentes. A doença se concentrou em quatro bairros: Terrenos Novos, Centro, Expectativa e Sinhá Saboia, expressando áreas mais densas (quentes). A incidência e a letalidade foram crescentes no início do período e decrescentes no final, com uma inversão destes indicadores no ano de 2014. Conclusão: em Sobral, a leishmaniose visceral humana é um agravo considerado relevante para o serviço de vigilância em saúde com necessidade de intensificação das ações de controle entomológico, zoonótico e de manejo ambiental, principalmente nas áreas mais densas.

Objectives: the objective was to describe the epidemiological, spatial, and temporal aspects of human visceral leishmaniasis, in the municipality of Sobral, from 2007 to 2019. Methods: A descriptive, spatial and temporal ecological study was carried out using Quantum-Gis and Joinpoint programs. Results: 316 new cases were confirmed, predominantly in males, in the age groups of 1 to 4 years (26.3%) and 20 to 39 years (24.0%), mainly in the urban area. Fever (95.9%), weakness (85.1%), weight loss (80.1%), pallor (73.7%), splenomegaly (75.6%), and hepatomegaly (69.3%) were the most frequent clinical signs. The disease was concentrated in four neighborhoods (Terrenos Novos, Centro, Expectativa, and Sinhá Saboia), hot spots. The incidence and case-fatality increased at the beginning of the period but decreased at the end, with an inversion in these in the year 2014. Conclusion: In Sobral, human visceral leishmaniasis is a disease considered relevant to the health surveillance service, with the need to intensify entomological, zoonotic, and environmental management actions, especially in denser areas.