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.

Estudo epidemiológico descritivo dos casos notificados de Leishmaniose visceral no estado de Goiás no período de 2011 a 2020 / Descriptive epidemiological study of notified cases of visceral Leishmaniasis in the state of Goiás in the period from 2011 to 2020 / Estudio epidemiológico descriptivo de los casos notificados de Leishmaniasis visceral en el estado de Goiás en el período de 2011 a 2020

A leishmaniose visceral, conhecida também como calazar, trata-se da forma mais grave das leishmanioses por ser uma enfermidade sistêmica e com um grande espectro clínico e um caráter irregular. Desse modo, objetivou-se avaliar a situação epidemiológica da leishmaniose visceral no Estado de Goiás, bem como o caráter dessa doença e o perfil mais atingido. Para isso, foi realizada uma pesquisa retrospectiva compreendendo o período de 2012 a 2021, com os casos notificados de leishmaniose visceral no Estado de Goiás. A busca pelos dados ocorreu por meio dos SINAN/DATASUS do Ministério da Saúde. Os dados encontrados foram tabulados e analisados por meio do programa Excel da Microsoft®. No período avaliado, foram notificados 388 casos de LV em Goiás, distribuídos em 47 municípios goianos. 66,23% das ocorrências pertenciam ao sexo masculino; 25,51% eram adultos com idade entre 20- 39 anos; 74,48% eram moradores da zona urbana; além disso, 9,27% do total de casos notificados em Goiás evoluíram para óbito. Há ainda uma a taxa de coinfecção LV/HIV de 12,11% do total de casos notificados. Constatou-se, portanto, que algumas localidades possuem registros consequentes de LV, levando a existência de áreas endêmicas no estado. Existe um perfil de acometimento em Goiás, no período de análise, direcionado para o sexo masculino, de cor parda, jovens adultos, com baixa escolaridade, vivendo nas cidades e grandes centros urbanos. Destaca-se o elevado quantitativo de dados identificados como ignorado/branco, que podem interferir significativmente em análises epidemiológicas.

Visceral leishmaniasis, also known as kala-azar, is the most serious form of leishmaniasis because it is a systemic disease with a wide clinical spectrum and an irregular character. Thus, the objective was to evaluate the epidemiological situation of visceral leishmaniasis in the State of Goiás, as well as the character of this disease and the most affected profile. For this, a retrospective survey was carried out covering the period from 2012 to 2021, with reported cases of visceral leishmaniasis in the State of Goiás. The search for data took place through the SINAN/DATASUS of the Ministry of Health. The data found were tabulated and analyzed using the Microsoft® Excel program. In the period evaluated, 388 cases of VL were reported in Goiás, distributed in 47 munic- ipalities in Goiás. 66.23% of the occurrences were male; 25.51% were adults aged be- tween 20-39 years; 74.48% were residents of the urban area; in addition, 9.27% of the total cases reported in Goiás evolved to death. There is also a LV/HIV co-infection rate of 12.11% of the total reported cases. It was found, therefore, that some localities have consequent records of VL, leading to the existence of endemic areas in the state. There is a profile of involvement directed towards males, of mixed race, young adults, with low education, living in cities and large urban centers. The high quantity of data identified as ignored/white stands out, which can significantly interfere in epidemiological analyses. KEYWORDS: Epidemiology; Leishmania; Notification.

La leishmaniasis visceral, también conocida como kala-azar, es la forma más grave de leishmaniasis por tratarse de una enfermedad sistémica de amplio espectro clínico y carácter irregular. Así, el objetivo fue evaluar la situación epidemiológica de la leishmaniasis visceral en el Estado de Goiás, así como el carácter de esta enfermedad y el perfil más afectado. Para ello, se realizó una encuesta retrospectiva que abarcó el período de 2012 a 2021, con los casos notificados de leishmaniasis visceral en el Estado de Goiás. La búsqueda de datos se realizó a través del SINAN/DATASUS del Ministerio de Salud. Los datos encontrados fueron tabulados y analizados utilizando el programa Microsoft® Excel. En el período evaluado, fueron notificados 388 casos de LV en Goiás, distribuidos en 47 municipios de Goiás. 66,23% de las ocurrencias fueron del sexo masculino; 25,51% eran adultos con edad entre 20-39 años; 74,48% eran residentes del área urbana; además, 9,27% del total de casos notificados en Goiás evolucionaron a muerte. Existe también una tasa de coinfección LV/VIH de 12,11% del total de casos notificados. Se constató, por lo tanto, que algunas localidades tienen registros consecuentes de LV, llevando a la existencia de áreas endémicas en el estado. Existe un perfil de envolvimiento dirigido a hombres, mestizos, adultos jóvenes, con baja escolaridad, residentes en ciudades y grandes centros urbanos. Se destaca la elevada cantidad de datos identificados como ignorados/blancos, lo que puede interferir significativamente en los análisis epidemiológicos.

Panorama clínico, epidemiológico e espacial da ocorrência de Leishmaniose visceral no estado do Pará, Amazônia brasileira / Clinical, epidemiological and spatial overview of visceral Leishmaniasis in the state of Pará, brazilian amazonia / Panorama clínico, epidemiológico y espacial de la Leishmaniasis visceral en el estado de Pará, amazonia brasileña

Objetivo: Essa pesquisa teve como objetivo determinar o perfil clínico, epidemiológico e espacial daLeishmaniose Visceral, bem como, sua associação com o desmatamento nos municípios pertencentesao 12º centro regional de saúde no Sudeste do Estado do Pará, Brasil de 2016 a 2020. Método: Trata-se de um estudo analítico ecológico, realizado com dados provenientes de 15 municípios do 12º Centro Regional de Saúde, obtidos por meio do banco de dados do Data-SUS-TABNET, através do SINAN. Resultados: Para o período do estudo foram notificados 415 casos de LV nos municípios analisados, o que correspondeu a uma média anual de 83 casos. O ano com maior número de notifi- cações foi 2017, apresentando 34,7%, sendo o município de Redenção com o maior número de casos.Conclusões: Portanto, há necessidade de ampliação das medidas de controle e vigilância da LV, comfoco na notificação de casos, a fim de realizar a obtenção do panorama fidedigno da LV e elaborar estratégias mais assertivas para seu controle e mitigação.

Objective: This research aimed to determine the clinical, epidemiological and spatial profile of Vis- ceral Leishmaniasis, as well as its association with deforestation in the municipalities belonging to the 12th regional health center in the Southeast of Pará State, Brazil from 2016 to 2020. Method: Thisis an ecological analytical study, conducted with data from 15 municipalities of the 12th Regional Health Center, obtained through the Data-SUS-TABNET database, through SINAN. Results: For thestudy period, 415 cases of VL were reported in the analyzed municipalities, corresponding to an an-nual average of 83 cases. The year with the highest number of notifications was 2017, present- ing 34.7%, being the municipality of Redenção with the highest number of cases. Conclu- sion: Therefore,there is a need to expand VL control and surveillance measures, focusing on the notification of casesin order to obtain a reliable picture of VL and develop more assertive strategies for its control and mitigation.

Objetivo: Esta investigación tuvo como objetivo determinar el perfil clínico, epidemiológico y espacial de la Leishmaniasis Visceral, así como su asociación con la deforestación en municipios pertenecientes al 12º Centro Regional de Salud del Sudeste del Estado de Pará, Brasil, de 2016 a 2020. Método: Trata-se de um estudo analítico ecológico, realizado com dados provenientes de 15 municípios do 12º Centro Regional de Saúde, obtidos por meio do banco de dados do Data-SUS-TABNET, através do SINAN. Resultados: Durante el período de estudio, fueron notificados 415 casos de LV en los municipios analizados, correspondiendo a una media anual de 83 casos. El año con mayor número de notificaciones fue 2017, 34,7%, y el municipio de Redenção presentó el mayor número de casos. Conclusiones: Por lo tanto, es necesario ampliar las medidas de control y vigilancia de la LV, centrándose en la notificación de casos con el fin de obtener una imagen fiable de la LV y desarrollar estrategias más asertivas para su control y mitigación.

Temporal trend in the incidence of human visceral leishmaniasis in Brazil.

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.

Comparison of collection methods for Phlebotomus argentipes sand flies to use in a molecular xenomonitoring system for the surveillance of visceral leishmaniasis.

BACKGROUND: The kala-azar elimination programme has resulted in a significant reduction in visceral leishmaniasis (VL) cases across the Indian Subcontinent. To detect any resurgence of transmission, a sensitive cost-effective surveillance system is required. Molecular xenomonitoring (MX), detection of pathogen DNA/RNA in vectors, provides a proxy of human infection in the lymphatic filariasis elimination programme. To determine whether MX can be used for VL surveillance in a low transmission setting, large numbers of the sand fly vector Phlebotomus argentipes are required. This study will determine the best method for capturing P. argentipes females for MX. METHODOLOGY/PRINCIPAL FINDINGS: The field study was performed in two programmatic and two non-programmatic villages in Bihar, India. A total of 48 households (12/village) were recruited. Centers for Disease Control and Prevention light traps (CDC-LTs) were compared with Improved Prokopack (PKP) and mechanical vacuum aspirators (MVA) using standardised methods. Four 12x12 Latin squares, 576 collections, were attempted (12/house, 144/village,192/method). Molecular analyses of collections were conducted to confirm identification of P. argentipes and to detect human and Leishmania DNA. Operational factors, such as time burden, acceptance to householders and RNA preservation, were also considered. A total of 562 collections (97.7%) were completed with 6,809 sand flies captured. Females comprised 49.0% of captures, of which 1,934 (57.9%) were identified as P. argentipes. CDC-LTs collected 4.04 times more P. argentipes females than MVA and 3.62 times more than PKP (p<0.0001 for each). Of 21,735 mosquitoes in the same collections, no significant differences between collection methods were observed. CDC-LTs took less time to install and collect than to perform aspirations and their greater yield compensated for increased sorting time. No significant differences in Leishmania RNA detection and quantitation between methods were observed in experimentally infected sand flies maintained in conditions simulating field conditions. CDC-LTs were favoured by householders. CONCLUSIONS/SIGNIFICANCE: CDC-LTs are the most useful collection tool of those tested for MX surveillance since they collected higher numbers of P. argentipes females without compromising mosquito captures or the preservation of RNA. However, capture rates are still low.

Post kala-azar dermal leishmaniasis in the Indian sub-continent: challenges and strategies for elimination.

Visceral leishmaniasis (VL) is a severe and often fatal form of leishmaniasis caused by Leishmania donovani in the Indian sub-continent. Post Kala-azar Dermal Leishmaniasis (PKDL) is a late cutaneous manifestation of VL, typically occurring after apparent cure of VL, but sometimes even without a prior history of VL in India. PKDL serves as a significant yet neglected reservoir of infection and plays a crucial role in the transmission of the disease, posing a serious threat to the VL elimination program in the Indian sub-continent. Therefore, the eradication of PKDL should be a priority within the current VL elimination program aimed at achieving a goal of less than 1 case per 10,000 in the population at the district or sub-district levels of VL endemic areas. To accomplish this, a comprehensive understanding of the pathogenesis of PKDL is essential, as well as developing strategies for disease management. This review provides an overview of the current status of diagnosis and treatment options for PKDL, highlighting our current knowledge of the immune responses underlying disease development and progression. Additionally, the review discusses the impact of PKDL on elimination programs and propose strategies to overcome this challenge and achieve the goal of elimination. By addressing the diagnostic and therapeutic gaps, optimizing surveillance and control measures, and implementing effective intervention strategies, it is possible to mitigate the burden of PKDL and facilitate the successful elimination of VL in the Indian sub-continent.

Canine Leishmania spp. infection in two distinct foci of visceral and cutaneous leishmaniasis in Tunisia.

Visceral leishmaniasis (VL) and zoonotic cutaneous leishmaniasis (ZCL) caused by Leishmania (L.) infantum and L. major, respectively, are endemic in Tunisia. The aim of the study was to assess canine Leishmania spp. infection prevalence as well as to identify the Leishmania species involved in two well-documented and geographically distinct VL and ZCL foci. One hundred seventy-six dogs were randomly recruited in the VL focus of Sbikha-Zaghouan (n = 100) and the ZCL focus of Echrarda-Nasrallah (n = 76). Physical examination and blood collection were systemically performed. Needle aspiration was done in case of lymph node (LN) enlargement. All sera were tested by ELISA. kDNA RT-PCR was performed on DNA extracts from (i) buffy coats of seropositive dogs and (ii) LN aspirates. Leishmania species identification was done by ITS1 PCR-sequencing. Thirty-three dogs (18.8%) were infected by Leishmania; 30 having anti-Leishmania antibodies and 3 were seronegative dogs with Leishmania DNA in LN aspirates. Prevalence of infection was significantly higher in VL foci than in ZCL foci (27% versus 7.9%, p = 0.002). Leishmania species was identified in 11 dogs and corresponded to L. infantum. Combination of serology and qPCR on LN aspirates seems to be the best option for canine leishmaniasis diagnosis. Infection is more frequent in VL foci and L. infantum is the only identified species.

Survey of phlebotomine sand fly fauna in a public Zoo in Brazil: Species diversity, seasonality, and host variety.

Leishmaniasis is a dynamic disease in which transmission conditions change due to environmental and human behavioral factors. Epidemiological analyses have shown modifications in the spread profile and growing urbanization of the disease, justifying the expansion of endemic areas and increasing number of cases in dogs and humans. In the city of Belo Horizonte, located in the southeastern state of Minas Gerais (Brazil), visceral leishmaniasis (VL) is endemic, with a typical urban transmission pattern, but with different regional prevalence. This study was conducted at the Zoo of the Foundation of Municipal Parks and Zoobotany of Belo Horizonte (FPMZB-BH), located in the Pampulha region, which is among the areas most severely affected by VL. This study aimed to determine the taxonomic diversity of native phlebotomine sand flies (Diptera: Psychodidae), identify climatic variables that potentially affect the phenology of these insects, and determine the blood meal sources for female phlebotomine sand flies. To achieve this, 10 mammal enclosures in the zoo were selected using the presence of possible leishmaniasis reservoirs as a selection criterion, and sampled using light traps between August 2019 and August 2021. A total of 6034 phlebotomine sand flies were collected, indicating nine species, with Lutzomyia longipalpis being the very abundant species (65.35% of the total). Of the 108 engorged phlebotomine collected females, seven samples (6.5%) were positive for blood meals from humans, marsupials, canids, and birds. Relative humidity and rainfall increased the phenology of phlebotomine sand flies, with population increases in the hottest and wettest months. The data obtained will provide guidelines for competent health agencies to implement vector control measures to reduce the risk of leishmaniasis transmission in the FPMZB-BH.

Diagnosis of visceral leishmaniasis in Ceará state, Brazil: A flow analysis of cases between 2007 and 2021.

OBJECTIVES: To analyse the flow of cases of visceral leishmaniasis (VL) in the state of Ceará, Brazil, between 2007 and 2021. METHODS: An ecological study was conducted using a spatial approach of newly confirmed cases of VL recorded in the Notifiable Diseases Information System. We identified individuals whose municipality of diagnosis differed from that of their residence. Flow maps, constructed using Tabwin 32 and ArcMap 9.2, allowed for the identification of the volume of traffic between the municipality of residence and that of initial care. RESULTS: There were 6775 confirmed VL cases. As a flow indicator, 178 counties had at least one resident diagnosed in another municipality in Ceará, with 2491 VL cases and an average trip of 79 km. The largest hub for receiving cases for diagnosis was the capital Fortaleza (1478 patients from 129 other municipalities), followed by Sobral, located in the northwestern region of Ceará (599 from 55 municipalities), and Barbalha, in the southern region (171 from 29 municipalities). In this southern region, 25 municipalities moved 55 people for treatment to Juazeiro do Norte and 11 municipalities moved 39 patients to Crato. A total of 255 patients with VL from 11 municipalities in other Brazilian states, mainly from the Northeast and North, were observed and notified in health services in Ceará. CONCLUSIONS: The major centres of VL diagnosis outside residence were in the cities of Fortaleza, Sobral, Barbalha, Juazeiro do Norte and Crato. There was also an outflow of cases from other municipalities located in the northeastern and northern regions of Brazil. The flows were more intense during the first triennium of the analysis and milder from 2019 to 2021. Understanding the diagnostic flow of VL helps in decision making and the development of public policies to improve the lives of the population.

Immunogenic mapping of rDyn-1 and rKDDR-plus proteins and selection of oligopeptides by immunoblotting for the diagnosis of Leishmania infantum-infected dogs.

Endemic in Brazil, visceral leishmaniasis (VL) is a zoonotic infection that is among the most important parasitic diseases transmitted by vectors. Dogs are the main reservoirs of canine leishmaniasis (CanL) and their identification is used in some countries as part of disease prevention and control measures in the canine and human population. In this context, serological tests are necessary, composed of antigens capable of correctly identifying infected dogs, minimizing the number of false-negative cases. This study aimed to identify more immunoreactive peptides derived from two previously described whole proteins (rDyn-1 and rKDDR-plus) and compare their performance to the control antigens rK39 and the crude extract for the detection of dogs infected with L. infantum, especially the asymptomatic ones. The three selected peptides and a mixture of them, along with the rDyn-1, rKDDR-plus, rK39, and crude extract antigens were evaluated using indirect ELISA with sera samples from 186 dogs with CanL, being asymptomatic (n = 50), symptomatic (n = 50), co-infected (n = 19), infected with Babesia sp. (n = 7), Ehrlichia sp. (n = 6), T. cruzi (n = 20) and uninfected (n = 34). The results showed that the rDyn-1 protein and the peptide mixture had the highest sensitivity (100% and 98.32%, respectively) and specificity (97.01 and 98.51, respectively). A high degree of kappa agreement was found for rDyn-1 protein (0.977), mixed peptides (0.965), rKDDR-plus protein (0.953), K-plus peptide 1 (0.930) and Dyn-1 peptide (0.893). The mixture of peptides showed the highest likelihood (65.87). The ELISA using the mixture of peptides and the rDyn-1 protein showed high performance for CanL serodiagnosis. More mix combinations of the peptides and additional extended field tests with a larger sample size are recommended.

Same parasite, different outcomes: unraveling the epidemiology of Leishmania infantum infection in Brazil and Spain.

Human leishmaniosis caused by Leishmania infantum is an important health problem worldwide. One of the main aspects arousing interest is the epidemiological scenario surrounding Le. infantum infection in the New World (NW) and Old World (OW). This parasite was introduced to the Americas during European colonization leading to different epidemiology outcomes, even more enigmatic in the face of global changes. Thus, this review aims to highlight the differences and similarities between Le. infantum epidemiology between Brazil (NW) and Spain (OW), as both countries are leading the total number of leishmaniosis cases in their respective continents. Grounded on a systemic view, this article also draws attention to possible common innovative strategies to rethink ways of controlling infections caused by Le. infantum.

Impact of COVID-19 lockdown during 2020 on the occurrence of vector-borne diseases in India.

BACKGROUND & OBJECTIVES: India imposed one of the world's largest nationwide lockdown in the aftermath of COVID-19 pandemic in March 2020 which was partly extended up to December. Some of the impacts of the COVID-19 lockdown on the economy, research, travel, education, and sports were readily apparent; the same was less obvious in the occurrence of vector-borne diseases (VBDs). The objective of this study was to statistically determine the impact of the COVID-19 lockdown on the occurrence of VBDs in India. METHODS: The reported incidence of VBDs such as malaria, dengue, Chikungunya, Japanese encephalitis, and kala-azar in India during the years 2015-2019 was analyzed by fitting Poisson and negative binomial (NB) models for each VBDs separately. The number of cases reported was compared with the number of cases predicted for each year from 2015 to 2020 for all the VBDs under study to infer whether or not the lockdown had any impact on their prevalence in India. RESULTS: The percentage of the actual case was lower by 46, 75, 49, 72, and 38 respectively for malaria, dengue, Chikungunya, Japanese encephalitis, and kala-azar when comparing the lockdown period and the year before lockdown (2020 vs. 2019). The number of cases predicted for the year 2020 based on the trend of the five preceding years (2015-2019) also showed a great variation between actual and predicted cases. The differences in cases were considered as the cases missed in 2020 were largely due to the lockdown. INTERPRETATION & CONCLUSION: The analysis showed that the lockdown had a considerable impact on the occurrence of VBDs.

Fever of unknown origin and splenomegaly: a case report of visceral leishmaniasis diagnosed by metagenomic next-generation sequencing.

Visceral leishmaniasis (VL) is a parasitic disease caused by Leishmania spp., which is transmitted by sandflies. As China is not the main epidemic area and VL has complex and atypical clinical manifestations, it is easily misdiagnosed or even missed in clinical practice. Without prompt and efficient treatment, the mortality rate of VL is extremely high; therefore early diagnosis of VL is crucial. Herein we describe a case of fever and splenomegaly of unknown origin, which was finally diagnosed as VL by metagenomic next-generation sequencing.

The estimated distribution of autochthonous leishmaniasis by Leishmania infantum in Europe in 2005-2020.

BACKGROUND: This study describes the spatial and temporal distribution between 2005 and 2020 of human and animal leishmaniasis by Leishmania infantum in European countries reporting autochthonous cases, and highlights potential activities to improve disease control. METHODOLOGY/PRINCIPAL FINDINGS: It was based on a review of the scientific literature and data reported by the World Health Organization (WHO), the World Organization for Animal Health (WOAH) and the Ministries of Health, including hospital discharges in some countries. Autochthonous infections were reported in the scientific literature from 22 countries, including 13 and 21 countries reporting human and animal infections, respectively. In contrast, only 17 countries reported autochthonous human leishmaniasis cases to the WHO and 8 countries animal infections to the WOAH. The number of WOAH reported cases were 4,203, comprising 4,183 canine cases and 20 cases in wildlife. Of 8,367 WHO reported human cases, 69% were visceral leishmaniasis cases-of which 94% were autochthonous-and 31% cutaneous leishmaniasis cases-of which 53% were imported and mostly in France. The resulting cumulative incidence per 100,000 population of visceral leishmaniasis between 2005-2020, was highest in Albania (2.15 cases), followed by Montenegro, Malta, Greece, Spain and North Macedonia (0.53-0.42), Italy (0.16), Portugal (0.09) and lower in other endemic countries (0.07-0.002). However, according to hospital discharges, the estimated human leishmaniasis incidence was 0.70 in Italy and visceral leishmaniasis incidences were 0.67 in Spain and 0.41 in Portugal. CONCLUSIONS/SIGNIFICANCE: Overall, there was no evidence of widespread increased incidence of autochthonous human leishmaniasis by L. infantum in European countries. Visceral leishmaniasis incidence followed a decreasing trend in Albania, Italy and Portugal, and peaked in Greece in 2013, 2014 and 2017, and in Spain in 2006-2007 and 2011-2013. Animal and human cutaneous leishmaniasis remain highly underreported. In humans, hospital discharge databases provide the most accurate information on visceral leishmaniasis and may be a valuable indirect source of information to identify hotspots of animal leishmaniasis. Integrated leishmaniasis surveillance and reporting following the One Health approach, needs to be enhanced in order to improve disease control.

Clinical, hematological, biochemical, and histopathological evaluations in domestic cats (Felis catus) infected by Leishmania infantum.

A high frequency of feline leishmaniasis has been reported in several countries. However, much information about disease progression in cats still needs to be clarified. This study aimed to verify the occurrence of clinicopathological changes in cats infected with Leishmania infantum. A total of 60 cats were divided into three groups of 20 animals each: control, suspects, and infected. All 60 cats underwent blood count and biochemical analyses. Serum samples from 20 animals with leishmaniasis were also used to diagnose feline immunodeficiency virus and feline leukemia virus. A total of five of the infected animals underwent necropsy for a histopathological study. The main clinical findings in cats with leishmaniasis were lymphadenomegaly (65%), alopecia (55%), ulcerative skin lesions and weight loss (40%), skin nodules (25%), a significant reduction in red blood cells (p=0.0005) and hematocrit (p=0.0007), hyperplasia in spleen 4/5(80%), presence of Leishmania in the spleen 2/5(40%), hepatitis 3/5(60%), liver degeneration 4/5(80%) and inflammatory nephropathy 3/5(60%). It was concluded that cats with leishmaniasis presented significant clinical, hematological, and histopathological alterations compatible with L. infantum infection. The observation of lymphadenomegaly, weight loss, skin lesions and low concentration of red blood cells, contributes significantly to the diagnosis and analysis of progression of feline leishmaniasis.

High titers of anti-Leishmania spp. antibodies in apparently healthy dogs in the North Pioneer Mesoregion of the state of Paraná, Brazil.

Leishmaniasis is an anthropozoonosis with vector transmission, and knowledge regarding the occurrence of this parasitosis in sentinels can contribute to infection and disease control measures in humans. The objectives of this study were to evaluate the occurrence of Leishmania exposure and infection in dogs from urban and rural areas in the North Pioneer Mesoregion of the state of Paraná, to evaluate possible risk factors, and to analyze the statistical agreement between the serological techniques that were used. Using a convenience sampling, serum and whole blood samples were collected to perform serological and molecular assays, respectively. The enzyme-linked immunosorbent assay (ELISA) and indirect fluorescent antibody test (IFAT) identified 29/204 (14.2%) and 20/204 (9.8%) seropositive dogs, respectively. Five dogs (2.4%) were seropositive for both serological tests, and four dogs presented high titers in the IFAT. None of the samples tested positive for Leishmania spp. DNA according to polymerase chain reaction analysis. No factors were significantly associated with infection. Leishmania parasites circulate in urban and rural dogs in the North Pioneer Mesoregion of the state of Paraná. Despite the absence of clinical cases, seropositive animals with high antibody titers should serve as a warning to the local population that should be properly informed regarding the prevention.

Performance of five serological tests in the diagnosis of visceral and cryptic leishmaniasis: a comparative study.

INTRODUCTION: Leishmaniasis is a major health problem and its diagnosis still represents a challenge. Since consistent evidence on the comparison of serological methods is lacking, our work aims to compare five serological tests for the diagnosis of visceral and asymptomatic leishmaniasis in southern France, a region where leishmaniasis is endemic. METHODOLOGY: Serum samples from 75 patients living in Nice, France were retrospectively analyzed. They included patients affected by visceral leishmaniasis (VL; n = 25), asymptomatic carriers (AC; n = 25) and negative controls (n = 25). Each sample was tested using two immunochromatographic tests (ICT; IT LEISH® and TruQuick IgG/IgM®), an indirect fluorescent antibody test (IFAT) and two Western Blotting (WB; LDBio BIORAD® and an in-house method). RESULTS: Diagnosis of VL with IFAT and TruQuick® showed the highest diagnostic performance parameters. IFAT had 100% sensitivity and specificity, while TruQuick had 96% sensitivity and 100% specificity. Finally, the two tests showed high accuracy (100% for IFAT and 98% for TruQuick) for the AC group. WB LDBio® was the only method able to detect Leishmania latent infection, with a sensitivity of 92%, and a specificity of 100%, with a Negative Predictive Value (NPV) of 93%. This performance is reflected in the high accuracy of the test. CONCLUSIONS: The data obtained with TruQuick® supports its application in the rapid diagnosis of leishmaniasis in endemic areas, a feature not shown by IFAT despite its high diagnostic performance. Regarding the diagnosis of asymptomatic leishmaniasis, the best results were obtained with WB LDBio®, confirming previous studies.

Social determinants of visceral leishmaniasis elimination in Eastern Africa.

Visceral leishmaniasis is a vector-borne, protozoan disease with severe public health implications. Following the successful implementation of an elimination programme in South Asia, there is now a concerted endeavour to replicate these efforts in Eastern Africa based on the five essential elimination pillars of case management, integrated vector management, effective surveillance, social mobilisation and operational research. This article highlights how key social determinants (SD) of health (poverty, sociocultural factors and gender, housing and clustering, migration and the healthcare system) operate at five different levels (socioeconomic context and position, differential exposure, differential vulnerability, differential outcomes and differential consequences). These SD should be considered within the context of increasing the success of the five-pillar elimination programme and reducing inequity in health.

Visceral Leishmaniasis Caused by Leishmania Tropica.

PURPOSE: In Turkey, the main causative agent of visceral leishmaniasis (VL) is Leishmania. infantum and the main causative agent of cutaneous leishmaniasis (CL) is Leishmania tropica. In this study, we aimed to discuss the possible mechanisms, clinical aspects, and threat of visceralizing L. tropica. METHODS: This study includes seven cases of VL caused by L. tropica.Five patients were male (71%) and four were adults (57%). RESULTS: All the VL patients complained of fever and splenomegaly. Fatigue, pancytopenia, and hepatomegaly were present in six patients each (86%), while weight loss and gastrointestinal system (GIS) symptoms were present in 5 patients (71%). CONCLUSIONS: In this study, we have evaluated seven cases of visceralized L. tropica (VLT) in the context of the changing leishmaniasis epidemiology in Turkey. We have evaluated the possible mechanisms of visceralization; inter- and intraspecies genetic exchange with all the old world leishmaniasis agents present in the region, stress induced by inappropriate use of drugs, and possible ongoing adaptation mechanisms of Leishmania spp. The threat posed by VLT is significant as L. tropica is the most widespread and most common cause of leishmaniasis in Turkey. We do not know the vectorial capacity of the sand flies for the transmission of VLT strains or if these strains are in circulation in Turkey. Future studies should be carried out to investigate these issues as the transition of L. tropica from a mild disease-causing agent to a mortal one poses a significant public health concern for Turkey and Europe.

Bayesian multivariate longitudinal model for immune responses to Leishmania: A tick-borne co-infection study.

While many Bayesian state-space models for infectious disease processes focus on population infection dynamics (eg, compartmental models), in this work we examine the evolution of infection processes and the complexities of the immune responses within the host using these techniques. We present a joint Bayesian state-space model to better understand how the immune system contributes to the control of Leishmania infantum infections over the disease course. We use longitudinal molecular diagnostic and clinical data of a cohort of dogs to describe population progression rates and present evidence for important drivers of clinical disease. Among these results, we find evidence for the importance of co-infection in disease progression. We also show that as dogs progress through the infection, parasite load is influenced by their age, ectoparasiticide treatment status, and serology. Furthermore, we present evidence that pathogen load information from an earlier point in time influences its future value and that the size of this effect varies depending on the clinical stage of the dog. In addition to characterizing the processes driving disease progression, we predict individual and aggregate patterns of Canine Leishmaniasis progression. Both our findings and the application to individual-level predictions are of direct clinical relevance, presenting possible opportunities for application in veterinary practice and motivating lines of additional investigation to better understand and predict disease progression. Finally, as an important zoonotic human pathogen, these results may support future efforts to prevent and treat human Leishmaniosis.