Dynamics Of Visceral Leishmaniasis Research Articles

Modeling and analysis of visceral leishmaniasis dynamics using fractional‐order operators: A comparative study

An in‐depth understanding of the mechanism concerning the parasitic disease called visceral leishmaniasis (VL) remains challenging. Thus, we modeled the dynamics of this illness using two fractional‐order operators, including Caputo–Fabrizio and Atangana–Baleanu. In the proposed dynamical model, the endemic and disease‐free equilibrium points were considered the symmetrical components. The fractional Euler method was applied to simulate the developed model, thus determining the equilibrium points' stability. The numerical simulation results were compared with the measured data to validate the model. The results obtained from the optimum fractional operator disclosed the minimum absolute and relative errors. The primary outcome of our study is the successful application of fractional‐order operators, specifically the Atangana–Baleanu operators with = 0.98, in modeling the dynamics of VL. Notably, the numerical simulation results, validated against real data from Sudan, demonstrated that the Atangana–Baleanu operators with = 0.98 yielded the best performance, with minimum absolute and relative errors. This underscores the precision of our fractional calculus‐based dynamical model in predicting VL dynamics compared to the classical framework, particularly for fractional‐order values of = 0.99 and = 0.98.

Modeling visceral leishmaniasis and tuberculosis co-infection dynamics

The co-infection of visceral leishmaniasis (VL) and tuberculosis (TB) patients pose a major public health challenge. In this study, we develop a mathematical model to study the transmission dynamics of VL and TB co-infection by first analyzing the VL and TB sub-models separately. The dynamics of these sub-models and the full co-infection model are determined based on the reproduction number. When the associated reproduction number (R1) for the TB-only model and (R2) for the VL-only are less than unity, the model exhibits backward bifurcation. If max{R1,R2}=R1, then the TB-VL co-infection model exhibits backward bifurcation for values of R1. Furthermore, if max{R1,R2}=R2, and by choosing the transmission probability, βL as the bifurcation parameter, then the phenomenon of backward bifurcation occurs for values of R2. Consequently, the full model, whose associated reproduction number is R0, also exhibits backward bifurcation when R0=1. The equilibrium points and their stability for the models are determined and analyzed based on the magnitude of the respective reproduction numbers. Finally, some numerical simulations are presented to show the reliability of our theoretical results.

Spatial and spatiotemporal dynamics of visceral leishmaniasis in an endemic North-eastern region of Brazil.

Visceral Leishmaniasis (VL) is a neglected disease with increasing incidence in Brazil, particularly in the North-eastern. The aim of this study was to analyze the spatial and spatiotemporal dynamics of VL in an endemic region of North-eastern Brazil, between 2009 and 2017. Using spatial analysis techniques, an ecological and time series study was made regarding VL cases in Sergipe filed as notifiable disease events. With data from the Brazilian Institute of Geography and Statistics (Instituto Brasileiro de Geografia e Estatística, IBGE), a digital population and cartographic baseline was established. Segmented linear regression was used to examine the temporal trends. The statistical analysis methods of Global and Local Moran' I, local Bayesian empirical methodology and spatial-temporal scanning were used to produce thematic maps. High instances were found among adults, males, urban residents, non-Whites and persons with low levels of education. A decrease in the recovery rate and an increase in the proportion of urban cases and lethality was found. A heterogeneous VL distribution with spatiotemporal agglomeration on the seaside of the state was seen in Sergipe. To better manage the disease, new research is encouraged together with development of public health strategies. Further, improving health care networks, especially primary care, is suggested as this approach has a key role in health promotion, prevention and monitoring of the most prevalent diseases.

Complexity and critical thresholds in the dynamics of visceral leishmaniasis.

We study a general multi-host model of visceral leishmaniasis including both humans and animals, and where host and vector characteristics are captured via host competence along with vector biting preference. Additionally, the model accounts for spatial heterogeneity in human population and heterogeneity in biting behaviour of sandflies. We then use parameters for visceral leishmaniasis in the Indian subcontinent as an example and demonstrate that the model exhibits backward bifurcation, i.e. it has a human infection and a sandfly population threshold, characterized by a bi-stable region. These thresholds shift as a function of host competence, host population size, vector feeding preference, spatial heterogeneity, biting heterogeneity and control efforts. In particular, if control is applied through human treatment a new and lower human infection threshold is created, making elimination difficult to achieve, before eventually the human infection threshold no longer exists, making it impossible to control the disease by only reducing the infection levels below a certain threshold. A better strategy would be to reduce the human infection below a certain threshold potentially by early diagnosis, control animal population levels and keep the vector population under check. Spatial heterogeneity in human populations lowers the overall thresholds as a result of weak migration between patches.

Perfil epidemiológico da coinfecção por HIV e leishmaniose visceral no estado de Alagoas, 2009 – 2019

Objetivo: Qualificar o perfil epidemiológico da coinfecção por HIV e leishmaniose visceral no estado de Alagoas nos últimos 10 anos. Metodologia: Trata-se de um estudo descritivo, retrospectivo e quantitativo dos casos confirmados de leishmaniose visceral por coinfecção por HIV no estado de Alagoas no período de 2009 a 2019. Os dados utilizados são secundários do Sistema de Informação e Agravos de Notificação (SINAN) encontrados através do Departamento de Informática do Sistema Único de Saúde (DATASUS). Resultados: Nos últimos 10 anos foram notificados 503 casos de Leishmaniose Visceral (LV) no estado de Alagoas, sendo 27 (5,37%) são coinfectados por HIV. Ao analisar o perfil de casos confirmados de Leishmaniose por coinfecção HIV, constatou-se que 77,8% são do sexo masculino, a faixa etária de 20 a 39 anos prevaleceu com 63% dos casos notificados. Conclusão: Os resultados encontrados no presente estudo mostram que em Alagoas houve prevalência da Leishmaniose por coinfecção HIV em homens na idade reprodutiva e de baixa escolaridade. Nesse sentido, compreender a dinâmica epidemiológica da LV, HIV/AIDS e da coinfecção LV/HIV-AIDS se torna prioritário a inclusão de ofertas de educação em saúde devido à falta de informação como os fatores de riscos relacionados às patologias de forma a evitar a coinfecção de HIV-LV no estado de Alagoas. Portanto a formulação de medidas eficazes para o controle dessas patologias que são tão relevantes para o serviço público de saúde e epidemiológico.

Insights from mathematical modelling and quantitative analysis on the proposed WHO 2030 targets for visceral leishmaniasis on the Indian subcontinent.

Visceral leishmaniasis (VL) is a neglected tropical disease (NTD) caused by Leishmania protozoa that are transmitted by female sand flies. On the Indian subcontinent (ISC), VL is targeted by the World Health Organization (WHO) for elimination as a public health problem by 2020, which is defined as <1 VL case (new and relapse) per 10,000 population at district level in Nepal and sub-district level in Bangladesh and India. WHO is currently in the process of formulating 2030 targets, asking whether to maintain the 2020 target or to modify it, while adding a target of zero mortality among detected cases. The NTD Modelling Consortium has developed various mathematical VL transmission models to gain insight into the transmission dynamics of VL, identify the main knowledge gaps, and predict the feasibility of achieving and sustaining the targets by simulating the impact of varying intervention strategies. According to the models, the current target is feasible at the appropriate district/sub-district level in settings with medium VL endemicities (up to 5 reported VL cases per 10,000 population per year) prior to the start of the interventions. However, in settings with higher pre-control endemicities, additional efforts may be required. We also highlight the risk that those with post-kala-azar dermal leishmaniasis (PKDL) may pose to reaching and sustaining the VL targets, and therefore advocate adding control of PKDL cases to the new 2030 targets. Spatial analyses revealed that local hotspots with high VL incidence remain. We warn that the current target provides a perverse incentive to not detect/report cases as the target is approached, posing a risk for truly achieving elimination as a public health problem although this is taken into consideration by the WHO procedures for validation. Ongoing modelling work focuses on the risk of recrudescence when interventions are relaxed after the elimination target has been achieved.

Risk mapping of visceral leishmaniasis in Brazil

Brazil experiences a large number of visceral leishmaniasis (VL) cases. Our objective was to examine both spatial patterns of dispersion and space-time trends for this disease. We used all autochthonous confirmed cases of VL in Brazil from 2001 to 2017. Throughout Brazil, 53,715 human cases of VL were recorded. The Northeast, Southeast, and Midwest regions of Brazil were the most affected areas and presented a higher risk of transmission. Regarding spatiotemporal variation, significant differences were observed each year, with a peak in 2005. The dynamics of VL showed a clear non-random pattern of spread in Brazil.

Visceral Leishmaniasis in Hospitalized HIV-Infected Patients in Pernambuco, Brazil.

Common in four continents, visceral leishmaniasis (VL) is an important but neglected disease. Human immunodeficiency virus (HIV) infection increases the risk of developing VL in people from leishmaniasis-endemic areas, with worse prognosis when there is coinfection. We conducted a cross-sectional study to determine the prevalence of HIV/VL coinfection in patients admitted in three referral hospitals for HIV/acquired immunodeficiency syndrome (AIDS) in Pernambuco, Brazil, and to compare epidemiological, clinical, and laboratory characteristics among HIV/VL coinfected and HIV mono-infected individuals. The sample consisted of HIV patients aged 18 years or more, in a period of data collection of 6 months. We performed four Leishmania tests-polymerase chain reaction (PCR), direct agglutination test, rK39, and latex agglutination test-and individuals with at least one positive test were considered coinfected. The HIV/VL coinfection prevalence we found was 16.9%. We observed large variation in prevalence according to the Leishmania test used, with low coincidence of positive tests. The most frequent symptoms found were weight loss (75.6%), fever (67.6%), and cough (55.3%). When we compared HIV/VL coinfected and HIV mono-infected groups we did not observe statistically significant differences. Low educational level (P = 0.004) and pallor (P = 0.009) were more frequent in the coinfected group. Serum albumin level was higher in coinfected individuals (P = 0.009). It is important to follow-up these individuals to understand the dynamics of VL in people living with HIV. New tests are necessary, ideally differentiating active from latent infection. Testing for VL in people with HIV is important and should be considered as part of the initial investigation in these individuals.

Comments on “A Mathematical Study to Control Visceral Leishmaniasis: An Application to South Sudan”

Deterministic (ordinary differential equation) models for the transmission dynamics of vector-borne diseases that incorporate disease-induced death in the host(s) population(s) are generally known to exhibit the phenomenon of backward bifurcation (where a stable disease-free equilibrium of the model coexists with a stable endemic equilibrium when the associated reproduction number of the model is less than unity). Further, it is well known that, in these models, the phenomenon of backward bifurcation does not occur when the disease-induced death rate is negligible (e.g., if the disease-induced death rate is set to zero). In a recent paper on the transmission dynamics of visceral leishmaniasis (a disease vectored by sandflies), titled "A Mathematical Study to Control Visceral Leishmaniasis: An Application to South Sudan," published in Bulletin of Mathematical Biology, Vol. 79, Pages 1110-1134, 2017, Ghosh etal. (2017) stated that their deterministic model undergoes a backward bifurcation even when the disease-induced mortality in the host population is set to zero. This result is contrary to the well-established theory on the dynamics of vector-borne diseases. In this short note, we illustrate some of the key errors in the Ghosh etal. (2017) study.

Serological investigation of visceral Leishmania infection in human and its associated risk factors in Welkait District, Western Tigray, Ethiopia

Visceral leishmaniasis (VL) is major neglected public health problem in terms of geographical spread and incidence in Ethiopia. Magnitude, public health impact and dynamics of VL were not well studied in Welkait District, Western Tigray, though the area is known for VL. Hence, this study aimed to determine sero-prevalence of human VL and associated risk factors in Welkait as new foci. A cross sectional study design was employed in this study. Two stage stratified random sampling method was used to select study participants. Hence, a total of 329 human study participants were included for serological survey using ITleish and leishmanin skin tests. Semi structured questionnaire was also used to identify VL associated risk factors. Univariate and multivariate logistic regression statistical methods were used to determine the degree of association. The overall sero-prevalence of human VL in the study area was found to be 8.81%. Statistical significant difference in the prevalence of the disease was found among Sub-districts, sex, re-settlement, sleeping outdoor and dog ownership (P<0.05). Participants who resettled from their original place were found 2 times (AOR=2.143; 95% CI=1.02, 14.20) more vulnerable to VL infection. Those who had an experience of sleeping outdoor were found almost 4 times (AOR=4.29; 95% CI=1.58, 11.69) more likely to be at risk of acquiring VL infection than those sleep indoor. Furthermore, individuals who owned dogs were 3 times more prone to the VL infection than their counterparts (AOR=3.37; 95% CI=1.29, 8.76). Alarming sero-positivity of human VL was recorded from new foci. Hence, it is recommended to improve the VL health services in the study area. The investigation also invites further study on VL dynamics in the study area.

The Severity of Visceral Leishmaniasis Correlates with Elevated Levels of Serum IL-6, IL-27 and sCD14.

BackgroundVisceral leishmaniasis (VL) is a severe disease caused by infection with protozoa of the genus Leishmania. Classic VL is characterized by a systemic infection of phagocytic cells and an intense activation of the inflammatory response. It is unclear why 90% of infected individuals do not develop the disease while a minority develop the classical form. Furthermore, among those that develop disease, a small group progresses to more severe form that is unresponsive to treatment. The presence of inflammatory mediators in serum could theoretically help to control the infection. However, there is also a release of anti-inflammatory mediators that could interfere with the control of parasite multiplication. In this study, we took advantage of the spectrum of outcomes to test the hypothesis that the immune profile of individuals infected with Leishmania (L.) infantum is associated with the development and severity of disease.Methodology/Principal FindingsSera from patients with confirmed diagnosis of VL were evaluated for the presence of numerous molecules, and levels compared with healthy control and asymptomatic infected individuals.Conclusions/Principal FindingsAlthough differences were not observed in LPS levels, higher levels of sCD14 were detected in VL patients. Our data suggest that L. infantum may activate the inflammatory response via CD14, stimulating a generalized inflammatory response with production of several cytokines and soluble molecules, including IFN-γ, IL-27, IL-10, IL-6 and sCD14. These molecules were strongly associated with hepatosplenomegaly, neutropenia and thrombocytopenia. We also observed that IL-6 levels greater than 200 pg/ml were strongly associated with death. Together our data reinforce the close relationship of IFN-γ, IL-10, IL-6, TNF-α and IL-27 in the immune dynamics of VL and suggest the direct participation of sCD14 in the activation of the immune response against L. infantum.

Understanding the transmission dynamics of Leishmania donovani to provide robust evidence for interventions to eliminate visceral leishmaniasis in Bihar, India.

Visceral Leishmaniasis (VL) is a neglected vector-borne disease. In India, it is transmitted to humans by Leishmania donovani-infected Phlebotomus argentipes sand flies. In 2005, VL was targeted for elimination by the governments of India, Nepal and Bangladesh by 2015. The elimination strategy consists of rapid case detection, treatment of VL cases and vector control using indoor residual spraying (IRS). However, to achieve sustained elimination of VL, an appropriate post elimination surveillance programme should be designed, and crucial knowledge gaps in vector bionomics, human infection and transmission need to be addressed. This review examines the outstanding knowledge gaps, specifically in the context of Bihar State, India.The knowledge gaps in vector bionomics that will be of immediate benefit to current control operations include better estimates of human biting rates and natural infection rates of P. argentipes, with L. donovani, and how these vary spatially, temporally and in response to IRS. The relative importance of indoor and outdoor transmission, and how P. argentipes disperse, are also unknown. With respect to human transmission it is important to use a range of diagnostic tools to distinguish individuals in endemic communities into those who: 1) are to going to progress to clinical VL, 2) are immune/refractory to infection and 3) have had past exposure to sand flies.It is crucial to keep in mind that close to elimination, and post-elimination, VL cases will become infrequent, so it is vital to define what the surveillance programme should target and how it should be designed to prevent resurgence. Therefore, a better understanding of the transmission dynamics of VL, in particular of how rates of infection in humans and sand flies vary as functions of each other, is required to guide VL elimination efforts and ensure sustained elimination in the Indian subcontinent. By collecting contemporary entomological and human data in the same geographical locations, more precise epidemiological models can be produced. The suite of data collected can also be used to inform the national programme if supplementary vector control tools, in addition to IRS, are required to address the issues of people sleeping outside.

KUPFFER CELLS: TARGETING FOR THE EFFECTIVE MANAGEMENT OF VISCERAL LEISHMANIASIS

Visceral leishmaniasis is a protozoan disease which infects the macrophages of body and Kupffer cells (KCs) in the liver resident macrophages, which constitute 80% of tissue macrophages of the body. KCs are the first cellular protective line in liver sinusoid, which come into contact with gut-derived pathogenic microbes, microbial debris and senescent erythrocytes and impede the exogenous materials by producing cytokines and directly phagocytosing and degrading them. Visceral leishmaniasis (VL) is a vector-borne disease and it is widely accredited that the frequency as well as transmission dynamics of VL is closely interrelated to socioeconomic, climatic, and environmental factors. Macrophages act so as to secrete IL-1, TNF and IL-6 at the time of injury and infection, and process and present antigen to help T cells. Mononuclear phagocytic system consists of monocytes circulating in the blood and macrophages in tissue. Macrophages are dispersed throughout the body and take up residence in some tissues. Human leishmanial infections may manifest in any of the four most common forms. Depending on the causative species, it can manifest as cutaneous leishmaniasis mucocutaneous leishmaniasis, visceral leishmaniasis or diffused cutaneous leishmaniasis. The cutaneous form of the disease accounts for more than 50% of new cases of leishmaniasis. The current method of VL diagnosis involves evaluating clinical symptoms that include fever for more than 2 week, the presence of splenomegaly and a positive serological rK39 immunochromatographic rapid diagnostic test (RDT). The rK39 RDT is used to detect the presence of antibodies against the Leishmania antigen K39 that contains a repetitive 39 amino acid sequence from the kinesin protein.

Genetic diversity and structure in Leishmania infantum populations from southeastern Europe revealed by microsatellite analysis.

BackgroundThe dynamic re-emergence of visceral leishmaniasis (VL) in south Europe and the northward shift to Leishmania-free European countries are well-documented. However, the epidemiology of VL due to Leishmania infantum in southeastern (SE) Europe and the Balkans is inadequately examined. Herein, we aim to re-evaluate and compare the population structure of L. infantum in SE and southwestern (SW) Europe.MethodsLeishmania strains collected from humans and canines in Turkey, Cyprus, Bulgaria, Greece, Albania and Croatia, were characterized by the K26-PCR assay and multilocus enzyme electrophoresis (MLEE). Genetic diversity was assessed by multilocus microsatellite typing (MLMT) and MLM Types were analyzed by model- and distance- based algorithms to infer the population structure of 128 L. infantum strains.ResultsL. infantum MON-1 was found predominant in SE Europe, whilst 16.8% of strains were MON-98. Distinct genetic populations revealed clear differentiation between SE and SW European strains. Interestingly, Cypriot canine isolates were genetically isolated and formed a monophyletic group, suggesting the constitution of a clonal MON-1 population circulating among dogs. In contrast, two highly heterogeneous populations enclosed all MON-1 and MON-98 strains from the other SE European countries. Structure sub-clustering, phylogenetic and Splitstree analysis also revealed two distinct Croatian subpopulations. A mosaic of evolutionary effects resulted in consecutive sub-structuring, which indicated substantial differentiation and gene flow among strains of both zymodemes.ConclusionsThis is the first population genetic study of L. infantum in SE Europe and the Balkans. Our findings demonstrate the differentiation between SE and SW European strains; revealing the partition of Croatian strains between these populations and the genetic isolation of Cypriot strains. This mirrors the geographic position of Croatia located in central Europe and the natural isolation of the island of Cyprus. We have analysed the largest number of MON-98 strains so far. Our results indicate extensive gene flow, recombination and no differentiation between MON-1 and MON-98 zymodemes. No correlation either to host specificity or place and year of strain isolation was identified. Our findings may be associated with intensive host migration and common eco-epidemiological characteristics in these countries and give valuable insight into the dynamics of VL.

Seasonal Variation in the Prevalence of Sand Flies Infected with Leishmania donovani

BackgroundVisceral Leishmaniasis (VL) is a life threatening neglected infectious disease in the Indian subcontinent, transmitted by the bite of female sand flies. Estimation of the infectivity in the vector population, collected in different seasons, may be useful to better understanding the transmission dynamics of VL as well as to plan vector control measures.MethodologyWe collected sand flies from highly endemic regions of Bihar state, India for one year over three seasons. The species of the sand flies were confirmed by species-specific PCR-RFLP. Leishmania donovani infection was investigated in 1397 female Phlebotomus argentipes using PCR, targeting the Leishmania specific minicircle of the kDNA region. Further, the parasitic load in the infected sand flies was measured using quantitative PCR.ConclusionThough sand flies were most abundant in the rainy season, the highest rate of infection was detected in the winter season with 2.84% sand flies infected followed by the summer and rainy seasons respectively. This study can help in vector elimination programmes and to reduce disease transmission.

Spatial distribution of canine Visceral Leishmaniasis in Ilha Solteira, São Paulo, Brazil

Visceral Leishmaniasis (VL) is caused by protozoan of genus Leishmania and transmitted by sand flies of genus Lutzomyia, which has been adapted to the peridomicile environment where dogs are their mainly food source, increasing the risk for human cases. In this study, techniques of geoprocessing and spatial statistics were utilized as a contribution to understanding the epidemiological dynamics of VL in the urban area of Ilha Solteira, SP.