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BACKGROUND: Visceral leishmaniasis (VL), or kala-azar, is a common comorbidity in patients with AIDS in endemic areas. Many patients continue to experiences relapses of VL despite virological control, but with immunological failure. These patients remain chronically symptomatic with hypersplenism, for example with anemia, leukopenia, and thrombocytopenia, and are at risk of severe co-infection due to low CD4+ count. Therefore, in this study, splenectomized patients with VL and HIV infection were investigated to understand why the CD4+ count fails to recover in these patients, evaluating the importance of spleen mass for hypersplenism and immunological failure. METHODS: From a retrospective open cohort of 13 patients who had previously undergone splenectomy as salvage therapy for relapsing VL, 11 patients with HIV infection were investigated. This study compared the patients' complete blood cell count (CBC) and CD4+ and CD8+ cell counts before and after splenectomy with respect to spleen weight. RESULTS: CBC was substantially improved after splenectomy, indicating hypersplenism. However, to the best of our knowledge, this is the first study to show that spleen mass is strongly and negatively correlated with CD4+ cell count (ρ = -0.71, P = 0.015). CONCLUSIONS: This finding was unexpected, as the spleen is the most extensive lymphoid tissue and T-lymphocyte source. After reviewing the literature and reasoning, we hypothesized that the immunological failure was secondary to CD4+ loss initially by apoptosis in the spleen induced by productive HIV infection and, subsequently, by pyroptosis sustained by parasitic infection in spleen macrophages.

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Kala-azar, also known as visceral leishmaniasis (VL), is a disease caused by Leishmania infantum and L. donovani. Patients experience symptoms such as fever, weight loss, paleness, and enlarged liver and spleen. The disease also affects immunosuppressed individuals and has an overall mortality rate of up to 10%. This overview explores the literature on the pathogenesis of preclinical and clinical stages, including studies in vitro and in animal models, as well as complications and death. Asymptomatic infection can result in long-lasting immunity. VL develops in a minority of infected individuals when parasites overcome host defenses and multiply in tissues such as the spleen, liver, and bone marrow. Hepatosplenomegaly occurs due to hyperplasia, resulting from parasite proliferation. A systemic inflammation mediated by cytokines develops, triggering acute phase reactants from the liver. These cytokines can reach the brain, causing fever, cachexia and vomiting. Similar to sepsis, disseminated intravascular coagulation (DIC) occurs due to tissue factor overexpression. Anemia, hypergammaglobulinemia, and edema result from the acute phase response. A regulatory response and lymphocyte depletion increase the risk of bacterial superinfections, which, combined with DIC, are thought to cause death. Our understanding of VL's pathogenesis is limited, and further research is needed to elucidate the preclinical events and clinical manifestations in humans.

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This systematic review gathered information on the spatial distribution in southern Brazil of the sandfly Migonemyia migonei, a possible vector of Leishmania species that cause visceral leishmaniasis (VL). Articles were searched from the PubMed, Scielo, Web of Science, and Scopus databases using the keywords: "Migonemyia migonei AND Paraná", "Migonemyia migonei AND Santa Catarina", "Migonemyia migonei AND Rio Grande do Sul", "phlebotomine AND Parana", " flebotomíneo AND Paraná" and "sandfly AND Paraná", "phlebotomine AND Santa Catarina;", " flebotomíneo AND Santa Catarina" and "sandfly AND Santa Catarina", "phlebotomine AND Rio Grande do Sul;", " flebotomíneo AND Rio Grande do Sul", and "sandfly AND Rio Grande do Sul". The initial search identified 322 articles that met the selection criteria. Empty files or duplicated were then excluded. The titles were screened, and the full texts were obtained. This review included 36 articles, covering 72 of the 399 (18.04%) municipalities in Paraná state, one of the 295 (0.33%) in Santa Catarina, and two of the 497 (0.40%) in Rio Grande do Sul. Mg. migonei was found in 54 municipalities of Paraná state, in one municipality of Santa Catarina, and in one of Rio Grande do Sul. Based on the wide distribution of Mg. migonei in the municipalities of Paraná, greater monitoring is required regarding cases of VL in humans and animals in this region, in addition to epidemiological investigations of these cases of suspected autochthony, as well as increased prevention and control efforts. More studies on VL are required in Santa Catarina and Rio Grande do Sul.

Esta revisão sistemática reuniu informações sobre a distribuição espacial no sul do Brasil do flebotomíneo Migonemyia migonei, um possível vetor de espécies de Leishmania causadoras da leishmaniose visceral (LV). Os artigos foram pesquisados nas bases de dados PubMed, Scielo, Web of Science e Scopus usando as palavras-chave: "Migonemyia migonei AND Paraná", "Migonemyia migonei AND Santa Catarina", "Migonemyia migonei AND Rio Grande do Sul", "phlebotomine AND Parana" , "flebotomíneo AND Paraná" e "flebotomíneo AND Paraná", "flebotomíneo AND Santa Catarina;", "flebotomíneo AND Santa Catarina" e "flebotomíneo AND Santa Catarina", "flebotomíneo AND Rio Grande do Sul;", "flebotomíneo AND Rio Grande do Sul" e "sandfly AND Rio Grande do Sul". A busca inicial identificou 322 artigos que atenderam aos critérios de seleção. Em seguida, arquivos vazios ou duplicados foram excluídos. Os títulos foram triados e os textos completos foram obtidos. Esta revisão incluiu 36 artigos, abrangendo 72 dos 399 (18,04%) municípios do Paraná, um dos 295 (0,33%) de Santa Catarina, dois dos 497 (0,40%) do Rio Grande do Sul. Mg. migonei foi encontrado em 54 municípios do Paraná estado, em um município de Santa Catarina e em um do Rio Gr ande do Sul. Com base na ampla distribuição de Mg. migonei nos municípios paranaenses, é necessária maior atenção quanto aos casos de LV em humanos e animais, além de investigações epidemiológicas desses casos de suspeita de autoctonia, bem como maiores esforços de prevenção e controle. Mais estudos são necessários em Santa Catarina e Rio Grande do Sul.

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BACKGROUND: We analysed the spatial and spatiotemporal patterns of visceral leishmaniasis (VL) mortality at the municipality level in an endemic state in the southern Amazon region of Brazil. Individual-level factors associated with death due to VL were also investigated. METHODS: All VL cases and deaths reported between 2007 and 2018 were included. The global and local bivariate Moran's index assessed the space-time autocorrelation of smoothed triennial VL mortality. Kulldorff's scan statistics investigated spatial and spatiotemporal clusters. A multivariable logistic regression explored sociodemographic, diagnostic and clinical variables associated with death due to VL. RESULTS: We observed an overall VL mortality and lethality of 0.14 cases/100 000 inhabitants and 11.2%, respectively. A total of 14% of the municipalities registered at least one VL-related death. In the southeastern mesoregion of the state, we detected high-risk spatial (relative risk [RR] 14.14; p<0.001) and spatiotemporal (RR 15.91; p<0.001) clusters for VL mortality. Bivariate Moran's analysis suggested a high space-time autocorrelation of VL mortality. Death by VL was associated with age ≥48 y (odds ratio [OR] 7.2 [95% confidence interval {CI} 3.4 to 15.3]), displacement for notification (OR 3.3 [95% CI 1.5 to 7.2]) and occurrence of oedema (OR 2.8 [95% CI 1.3 to 6.1]) and bleeding (OR 5.8 [95% CI 2.6 to 12.8]). CONCLUSIONS: VL mortality has a heterogeneous spatiotemporal distribution. The death-related factors suggest late diagnosis as an underlying cause of mortality.

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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.

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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.

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BACKGROUND: Visceral leishmaniasis is a neglected tropical disease of great importance to public health due to its wide distribution and close relationship with social and economic conditions. This study aimed to analyse the spatiotemporal dynamics of human visceral leishmaniasis (HVL) in an endemic state in the Northeast Region of Brazil and its spatial correlation with the Social Vulnerability Index (SVI) and the Municipal Human Development Index (MHDI). METHODS: The study included all confirmed cases of HVL in Bahia from 2010 to 2017. A joinpoint regression model was used for trend analysis. Incidence rates were smoothed by a local empirical Bayesian model. Global and local Moran indices and space-time scan statistics were used for identification of spatial clusters. Bivariate and multivariate analyses were carried out to investigate the relationship between HVL incidence and the SVI and MHDI. RESULTS: Cases of HVL demonstrated stationary behaviour during the period analysed. A significant association was observed between the HVL incidence rate and social vulnerability, with high-risk clusters concentrated in the central region of the state. CONCLUSIONS: HVL has a strong correlation with social vulnerability in the state of Bahia. This study may provide assistance in planning actions and organizing health services to combat HVL.

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Visceral leishmaniasis (VL) is a neglected tropical disease which contributes to the mortality and morbidity significantly in India and Brazil. This study was planned to compare the trends of incidence, prevalence, death and disability-adjusted life years (DALY) of VL burden in India and Brazil from 1990 to 2019 using Global burden of disease study (GBD) data. The metrics are presented as age-standardized rates per 100,000 inhabitants with their respective uncertainty intervals (95% UI) and relative percentages of change. The decline in the Incidence rate is more in case of India (16.82 cases per 100,000 in 1990 to 0.60 cases in 2019) as compared to Brazil (3.12 cases per 100,000 in 1990 to 2.65 cases in 2019). The annualized rate of change in number of prevalent cases for India is - 0.95 (95% UI - 0.98 to - 0.91) whereas for Brazil it is - 0.06 (95% UI - 0.41 to 0.52). The annualized rate of change in number of DALY for India is - 0.94 (95% UI - 0.96 to - 0.92) whereas for Brazil it is - 0.09 (95% UI - 0.25 to 0.28). The annualized rate of change in number of deaths for India is - 0.93 (95% UI - 0.95 to - 0.92) whereas for Brazil it is increasing i.e. 0.04 (95% UI - 0.12 to 0.51). India achieves significant reduction in the age standardized incidence, prevalence, mortality and DALY of VL as compared to Brazil during the period of 1990 to 2019. A multi-centric study is required to assess bottleneck in the existing strategies of VLSCP in Brazil.

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INTRODUCTION: Visceral leishmaniasis (VL) is a systemic and neglected parasitic disease. Its main symptoms are fever, splenomegaly with or without hepatomegaly, and anemia, however, most individuals remain asymptomatic. Due to the lack of a gold standard and the limitations of current diagnostic techniques, where parasitology is ethically unfeasible for individuals without symptoms and serological tests do not differentiate between past and present disease, molecular methodologies are the most suitable. AREAS COVERED: We performed a systematic review analyzing the molecular techniques based on PCR used, so far, to detect asymptomatic cases of VL in humans. Structured searches were carried out on PubMed, LILACS, Scopus, and Web of Science databases without time and language restrictions. Two reviewers evaluated the studies, performed data extraction, and quality assessment by assigning scores. EXPERT OPINION: qPCR using RNA targets can be used in the diagnosis of asymptomatic cases of human VL, due to its characteristics. We recommend further studies to analyze the methodology, mainly observing the use of different rRNA targets. Therefore, we hope that this technique contributed to the construction of public policies that address the diagnosis and handling of asymptomatic patients.

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Abstract INTRODUCTION: Malnutrition and kala-azar (or visceral leishmaniasis) are significant public health problems in different parts of the world. Immunity and susceptibility to infectious and parasitic diseases are directly linked to the host's nutritional state, but little is known about the interaction between nutrition and kala-azar. This study aimed to evaluate nutritional status with kala-azar and correlate these findings with the clinical and laboratory manifestations of the disease, and zinc and retinol levels. METHODS: This was a cross-sectional study of 139 patients with kala-azar. Nutritional status classification was performed according to international recommendations. Parametric or nonparametric tests were applied whenever indicated in a two-sided test with a 5% significance level. RESULTS: Weight loss and malnutrition were more frequent in adults. Body mass index-for-age, fat area of the arm, and upper arm muscle area were significantly associated with probability of death. The presence of human immunodeficiency virus, hepatomegaly, and splenomegaly was correlated with nutritional assessment. Blood leukocyte and lymphocyte, serum creatine, and vitamin A levels were significantly higher in adult men. Vitamin A levels were highly associated with the level of hemoglobin and C-reactive protein (CRP) in multivariate analysis. All patients had reduced plasma zinc levels, but this finding had no association with the outcome variables. CONCLUSIONS: Malnutrition was correlated with severe disease and was more prevalent in older people with kala-azar. Vitamin A deficiency was associated with hemoglobin and CRP. Zinc levels were reduced in patients with kala-azar.

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