Control Of Visceral Leishmaniasis Research Articles

The one health approach: combating the persistent Visceral Leishmaniasis (Kala-azar) outbreaks in Isiolo County, Kenya

Background: Visceral leishmaniasis has remained a public health problem in Kenya despite Ministry of Health’s numerous efforts. This is associated with absence of a multidisciplinary response to outbreaks. We intended to analyze community’s prioritization of causes of Visceral leishmaniasis as well as community awareness on the disease prevention and control. Methods: This was a descriptive cross-sectional study design conducted between September 2023 to December 2023. 433 households’ heads, 23 community leaders and health workers were study informants. Results: Study findings showed clear proximity of human settlements and socioeconomic activities to the vector sandfly breeding sites. Environmental factors augmented by effects of climate change including flooding and high temperatures have sustained transmission including emergence of the disease in new foci. Low socio-economic status, environmental factors and climate change effects showed highly significant correlations with the disease and interplay with one another. Study results show lack of strategies and policies that promote effective prevention and control of Kala-azar. Stakeholders’ analysis revealed limited community awareness regarding roles played by different individuals in Kala-azar prevention, control, and elimination. Conclusions: There is a major gap in cooperation of partners in human, animal, and environmental health for achievements in public health strategies, therefore One Health approach should be adopted for integrated prevention, control, and elimination. The approach will sustainably improve and promote health while addressing the entire spectrum of disease control, including detection, preparedness, response, and management in addition to disease prevention averting this terrible disease from resurfacing in the future.

Visceral Leishmaniasis (Kala-azar) in Merti Sub-County, Isiolo County: A Case of Socio-Cultural Challenges

Introduction: Visceral Leishmaniasis (VL) also known as Kala-azar is a fatal neglected tropical disease (NTD) with a 95% fatality rate among untreated cases. Although there is little information available about the disease's prevalence in Isiolo County, it is extremely endemic in a number of villages in Merti Sub-County. Case Presentation: In this case presentation, a family of three children resulted to traditional therapy when the children contracted Kala-azar. All the three children exhibited signs of fever, loss of appetite, swollen abdomen, vomiting, and general weakness. Discussion: Low levels of Visceral Leishmaniasis knowledge, ignorance characterized by cultural beliefs, and the use of local therapies are among socio-cultural challenges impeding implementation of effective Kala-azar control strategies in Isiolo County. Conclusion: This case highlights the importance of focused community awareness for prompt and efficient diagnosis and treatment to lower Kala-azar prevalence, monitoring the burden and spread of the disease as well as lowering transmission.

Challenges for maintaining post elimination phase of visceral leishmaniasis control programme in India: A field-based study.

India is going through the maintenance phase of VL elimination programme which may be threatened by the persistence of hidden parasite pools among asymptomatic leishmanial infection (ALI) and PKDL. The present work was designed to determine the burden of VL, PKDL, and ALI and to assess the role of treatment of ALI in maintaining post-elimination phase. The study was undertaken in Malda district, West Bengal, India during October 2016 to September 2021. Study areas were divided into 'Study' and 'Control' arms. VL and PKDL cases of both the arms were diagnosed by three active mass surveys with an interval of one year and treated as per National guideline. ALI of 'Study' arm was treated like VL. ALI of 'Control' arm was followed up to determine their fate. Fed sand-fly pools were analysed for parasitic DNA. No significant difference was noted between the incidence of VL and PKDL in both the arms. Incidence of ALI declined sharply in 'Study' arm but an increasing trend was observed in 'Control' arm. Significantly higher rate of sero-conversion was noted in 'Control' arm and was found to be associated with untreated ALI burden. Parasitic DNA was detected in 22.8% ALI cases and 2.2% sand-fly pools. Persistence of a significant number of PKDL and ALI and ongoing transmission, as evidenced by new infection and detection of leishmanial DNA in vector sand-flies, may threaten the maintenance of post-elimination phase. Emphasis should be given for elimination of pathogen to prevent resurgence of VL epidemics.

Construction of an evaluation index system for the capability of comprehensive control of mountain - type zoonotic visceral leishmaniasis based on the One Health concept

To construct an evaluation index system for the capability of comprehensive control of mountain-type zoonotic visceral leishmaniasis based on the One Health concept, so as to provide insights into the control and elimination of mountain-type zoonotic visceral leishmaniasis using the One Health approach. A preliminary evaluation index system was constructed based on literature review, panel discussions and field surveys. Thirty-three experts were selected from 7 provincial disease control and prevention centers in Beijing Municipality, Hebei Province, Shanxi Province, Henan Province, Sichuan Province, Shaanxi Province and Gansu Province where mountain-type zoonotic visceral leishmaniasis was endemic, and two rounds of expert consultations were conducted to screen the indicators. The positive coefficient, degree of concentration, degree of coordination, and authority of the experts were calculated, and the normalized weights of each index were calculated with the analytic hierarchy process. The response rates of questionnaires during two rounds of expert consultation were both 100.00% (33/33), and the authority coefficients of the experts were 0.86 and 0.88, respectively. The coefficients of coordination among experts on the rationality, importance, and operability of the indicators were 0.392, 0.437, 0.258, and 0.364, 0.335, 0.263, respectively (all P values < 0.05). Following screening, the final evaluation index system included 3 primary indicators, 17 secondary indicators, and 50 tertiary indicators. The normalized weights of primary indicators "external environment", "internal support" and "comprehensive control" were 16.98%, 38.73% and 44.29%, respectively. Among the secondary indicators of the primary indicator "external environment", the highest weight was seen for natural environment (66.67%), and among the secondary indicators of the primary indicator "internal support", the lowest weight was seen for the scientific research for visceral leishmaniasis control (8.26%), while other indicators had weights of 12.42% to 13.38%. Among the secondary indicators of the primary indicator "comprehensive control", the weight was 16.67% for each indicator. An evaluation index system has been constructed for the capability of comprehensive control of mountain-type zoonotic visceral leishmaniasis based on the One Health concept. In addition to assessment of the effect of conventional mountain-type zoonotic visceral leishmaniasis control measures, this index system integrates the importance of top-level design, organizational management, and implementation of control measures, and includes indicators related to multi-sectoral cooperation.

Toxicity of Trixis vauthieri DC essential oil on Lutzomyia longipalpis (Diptera, Psychodidae, Phlebotominae), a proven vector of visceral leishmaniasis in Brazil

Background &amp; objectives: In Brazil, one of the visceral leishmaniasis control measures in urban environments is the elimination of Lutzomyia longipalpis, which occurs through the application of pyrethroid insecticides with residual action in homes and outbuildings. Due to the loss of sensitivity of this vector to these insecticides, the search for more efficient insecticide compounds against L. longipalpis has been intensified. The objective of this work was to evaluate the toxicity of Trixis vauthieri essential oil on adult sandflies of the species L. longipalpis, and identify the phytochemical composition of these essential oils. Methods: Essential oils from leaves collected from T. vauthieri at different times were obtained at concentrations of 5, 10 and 20 mg/mL. Twenty sandflies were exposed to the essential oils and the mortality was evaluated after 1, 2, 4, 16, 24, 48 and 72 h. The chemical constituents of the essential oil were also identified. Results: The essential oils of T. vauthieri at a concentration of 20 mg/mL were the most toxic to sandflies, reaching a mortality rate of 98.33% and 95%, respectively, after 72 h of exposure. The analysis of chemical constituents revealed the presence of triterpenes and/or steroids, tannins, flavonoids, alkaloids, saponins and coumarins. Interpretation &amp; conclusion: The results obtained suggest that T. vauthieri essential oil is fairly promising as an insecticidal potential against L. longipalpis. A more detailed analysis of the oil’s phytochemical composition is necessary to identify active and pure compounds that can be used in vector control of visceral leishmaniasis.

Epidemiology of visceral leishmaniasis in municipalities of Mato Grosso and the performance of surveillance activities: an updated investigation.

Visceral leishmaniasis (VL) is considered a globally neglected disease. To address the problem of VL endemic to Brazil, the Visceral Leishmaniasis Control Program (VLCP) was created, which recommends the development of health surveillance actions such as the identification of human and canine cases, vector control and prevention of disease. We aimed to investigate the epidemiological situation of VL in municipalities of the State of Mato Grosso (MT) and assess the execution of VLCP activities. Data on human cases were obtained from the Information System for Notifiable Diseases (SINAN), and data from entomological and canine inquiry were provided by the State's Health Department. Analyzes from the period 2019 - 2021 recorded 30 cases of human VL, distributed among 16 municipalities. Vectors were identified in 50% of the municipalities where entomological investigations were carried out, and the predominant specie was Lutzomyia longipalpis. A total of 15,585 dogs were subjected to serological examination, of which 18.91% tested seropositive for Leishmania infantum. However, it must be emphasized that only three municipalities conducted consecutive inquiries involving canine VL. Although VL is distributed widely throughout the State, only a few municipalities have undertaken the actions of the VLCP, thus highlighting the neglected status of the disease.

A molecular signature for IL-10-producing Th1 cells in protozoan parasitic diseases.

Control of visceral leishmaniasis (VL) depends on proinflammatory Th1 cells that activate infected tissue macrophages to kill resident intracellular parasites. However, proinflammatory cytokines produced by Th1 cells can damage tissues and require tight regulation. Th1 cell IL-10 production is an important cell-autologous mechanism to prevent such damage. However, IL-10-producing Th1 (type 1 regulatory; Tr1) cells can also delay control of parasites and the generation of immunity following drug treatment or vaccination. To identify molecules to target in order to alter the balance between Th1 and Tr1 cells for improved antiparasitic immunity, we compared the molecular and phenotypic profiles of Th1 and Tr1 cells in experimental VL caused by Leishmania donovani infection of C57BL/6J mice. We also identified a shared Tr1 cell protozoan signature by comparing the transcriptional profiles of Tr1 cells from mice with experimental VL and malaria. We identified LAG3 as an important coinhibitory receptor in patients with VL and experimental VL, and we reveal tissue-specific heterogeneity of coinhibitory receptor expression by Tr1 cells. We also discovered a role for the transcription factor Pbx1 in suppressing CD4+ T cell cytokine production. This work provides insights into the development and function of CD4+ T cells during protozoan parasitic infections and identifies key immunoregulatory molecules.

Articulate Chemotherapeutic Strategies for the Development of Effective Drugs against a Fatal Disease, Visceral Leishmaniasis.

Visceral Leishmaniasis (VL) control relies mainly on chemotherapy in the absence of no effective vaccines. However, available anti-VL drugs are limited in number, having toxicity issues, adverse reactions, low efficacy, and resistance observed against antileishmanial. A significant decrease in efficacy (~tenfold increase in dosage and duration) was reported against the usual treatment with Pentavalent antimonials (the most recommended antileishmanial drug discovered 90 years ago). Amphotericin B is the second line of treatment but limits wider use due to its high cost. Pentamidine is another anti-VL drug, but its therapeutic efficacy has decreased significantly in different areas. These conventional therapeutics for VL have become almost outdated due to a significant increase in therapeutic failure in terms of percentage. Due to this, the search for an effective future anti-VL drug spans several decades, and now it is in high demand in the current situation. Some conventional therapeutics are modified, but they are also not satisfactory. Therefore, this article aimed to discuss conventional and modified therapeutics while emphasizing innovative chemotherapeutic measures against VL that could speed up the slow pace of antileishmanial drugs and overcome the drug resistance problem in the future.

Clinical-epidemiological aspects and prognostic factors associated with death from visceral leishmaniasis between the years 2010 to 2019 in the Central-West region of Brazil

In Brazil, the fatality rate for visceral leishmaniasis is high, and it is important to investigate its associated factors. The aim of this study was to analyze the clinical-epidemiological profile and prognostic factors associated with death from visceral leishmaniasis (VL) in the Central-West region of Brazil, between 2010 and 2019. A study of series of VL cases was carried out using data obtained from the Sistema Nacional de Agravos de Notificação (SINAN). Multivariate logistic regression was performed to identify variables associated with deaths. Male (64.96%); age group ≤5 years (28.51%); mixed race/color (59.20%); and level of education incomplete primary education (45.16%) were the most affected. The most frequent symptoms were fever (87.65%), weakness (77.56%), enlarged spleen (70.22%) and liver (67.33%), weight loss (67.22%) and pallor (63.41%). Co-infection with HIV was observed in 15.84% of patients. The parasitological diagnosis was positive in 74.17% and the Indirect Immunofluorescence (IIF) in 82.80%. The drug most used for treatment was pentavalent antimony (41.96%). Regarding the evolution of VL, cure was recorded for 82.90% of patients and death from VL in 8.30%. Factors associated with death from VL were: age group ≥20 and < 60 (OR 2.95; 95% CI 1.98–4.38) and ≥ 60 (OR 5.84; 95% CI 3.63–9.38), edema (OR 2.27; 95% CI 1.64–3.13), pallor (OR 1.53; 95% CI 1.06–2.20), infectious condition (OR 1.56; 95% CI 1.12–2.15) and hemorrhagic phenomena (OR 2.87; 95% CI 2.02–4.08). New studies are needed in order to better manage VL control, monitoring, prevention and primary care strategies.

RES-Seq-a barcoded library of drug-resistant Leishmania donovani allowing rapid assessment of cross-resistance and relative fitness.

Visceral leishmaniasis (VL) is a parasitic disease endemic across multiple regions of the world and is fatal if untreated. New therapeutic options with diverse mechanisms of actions (MoAs) are required to consolidate progress toward control of this disease and combat drug resistance. Here, we describe the development of a scalable resistance library screen (RES-Seq) as a tool to facilitate the identification and prioritization of anti-leishmanial compounds acting via novel MoA. We have amassed a large collection of Leishmania donovani cell lines resistant to frontline drugs and compounds in the VL pipeline, with resistance-conferring mutations fully characterized. New phenotypic hits screened against this highly curated panel of resistant lines can determine cross-resistance and potentially shared MoA. The ability to efficiently identify compounds acting via previously established MoA is vital to maintain diversity within drug development portfolios. To expedite screening, short identifier DNA barcodes were introduced into resistant clones enabling pooling and simultaneous screening of multiple cell lines. Illumina sequencing of barcodes enables the growth kinetics and relative fitness of multiple cell lines under compound selection to be tracked. Optimal conditions allowing discrimination of resistant and sensitive clones were established (3× and 10× EC50 for 3 days) and applied to screening of a complex library with VL preclinical and clinical drug candidates. RES-Seq is set to play an important role in ensuring that anti-leishmanial compounds exploiting diverse mechanisms of action are developed, ultimately providing options for future drug combination strategies.IMPORTANCEVisceral leishmaniasis (VL) remains the third largest parasitic killer worldwide, responsible for 20,000-30,000 deaths each year. Control and ultimate elimination of VL will require a range of therapeutic options with diverse mechanisms of action to combat drug resistance. One approach to ensure that compounds in development exploit diverse mechanisms of action is to screen them against highly curated cell lines resistant to drugs already in the VL pipeline. The identification of cross-resistant cell lines indicates that test compounds are likely acting via previously established mechanisms. Current cross-resistance screens are limited by the requirement to profile individual resistant cell lines one at a time. Here, we introduce unique DNA barcodes into multiple resistant cell lines to facilitate parallel profiling. Utilizing the power of Illumina sequencing, growth kinetics and relative fitness under compound selection can be monitored revolutionizing our ability to identify and prioritize compounds acting via novel mechanisms.

Assessing the role of active case detection on visceral leishmaniasis control: A case study

In this paper, we formulate and analyze a compartmental model of visceral leishmaniasis (VL). We validate our model by calibrating it to the yearly VL incidence data for India and Bangladesh. The proposed model’s basic reproduction number ([Formula: see text]) has been derived and estimated. We have proved the existence of backward bifurcation in our system. The phenomenon of backward bifurcation has public health implications because the classical requirement of [Formula: see text], while necessary, is no longer sufficient for effective disease control (or elimination). In such a (backward bifurcation) situation, the initial sizes of the model’s subpopulations (state variables) would determine the effectiveness of disease control or elimination. As a result, it is the first attempt to represent and study VL disease dynamics using active case detection (ACD) as a control strategy, although a few experimental studies have been conducted to evaluate ACD in disease transmission. We use sensitivity analysis to investigate the effects of the model’s controllable parameters for the basic reproduction number. We found that [Formula: see text] (monitoring rate to infected individuals) have negative impacts on [Formula: see text]. The numerical result suggests that the ACD strategy can be useful for the VL elimination program. Due to a small increment in the monitoring rate, the dynamic behavior of infected individuals dramatically decreased. Successful employment of ACD strategy may reduce more than 60–80% symptomatic and post kala-azar dermal leishmaniasis (PKDL) individuals. We found that healthcare organizations should prioritize ACD in symptomatic and PKDL individuals over asymptomatic individuals. We also observed that the use of only culling effect to the reservoirs is not beneficial to society in the control of VL, but spraying of insecticides and the use of treated bednets can be effective control strategies to curtail the outbreak of the disease.

Assessment of treatment outcomes of visceral leishmaniasis (VL) treated cases and impact of COVID-19 on VL management and control services in Bangladesh

BackgroundCOVID-19 has largely impacted the management of Visceral leishmaniasis (VL), like several other Neglected Tropical Diseases. The impact was particularly evident in Lower and Middle-Income countries where the already inadequate healthcare resources were diverted to managing the COVID-19 pandemic. Bangladesh achieved the elimination target for VL in 2016. To sustain this success, early diagnosis and treatment, effective vector control, and periodic surveillance are paramount. However, the specific control measures for VL in Bangladesh that were hampered during COVID-19 and their extent are unknown. MethodsThis study aimed at identifying the gaps and challenges in the follow-up of treated VL patients by interviewing both the treated VL cases and their health service providers. We followed VL cases treated between 2019 and 2020 in five VL endemic subdistricts (upazilas) both retrospectively and prospectively to monitor clinical improvement, relapse, or other consequences. Moreover, interviews were conducted with the health service providers to assess the impact of COVID-19 on VL case detection, treatment, reporting, vector control operations, and logistic supply chain management. ResultsThere was no added delay for VL diagnosis; however, VL treatment initiation and reporting time increased almost two-fold due to COVID-19. Indoor Residual Spraying activity was significantly hampered due to a shortage of insecticides. Out of 44 enrolled and treated VL patients, two relapsed (4.5 %), two developed Para Kala-Azar Dermal Leishmaniasis (4.5 %), and three (6.8 %) Post Kala-Azar Dermal Leishmaniasis (PKDL). The health service providers highlighted patients` unwillingness to visit the hospital, financial constraints, and distance from the hospitals as the main reasons for missed follow-up visits (20.5 %). Building good communication in the community, awareness schemes, and incentive-based approaches were suggested as possible solutions to mitigate these problems. ConclusionLong-term follow-up is required for the early detection and management of VL relapse and PKDL cases. Effective vector control measures, capacity development, and identification of new VL hotspots are pivotal in the VL endemic regions to sustain the elimination goal.

The Program for the Control of Visceral Leishmaniasis in Brazil: The Effect of the Systematic Euthanasia of Seropositive Dogs as a Single Control Action in Porteirinha, a Brazilian City with an Intense Transmission of Visceral Leishmaniasis.

Porteirinha is endemic for visceral leishmaniasis (VL), with intense disease transmission of the disease. We evaluated the impact of canine euthanasia as a single control measure on the incidence of VL in humans and canines. A prospective observational cohort study was carried out over four years (1998-2002) in 8 of the 12 neighborhoods of the city. The dynamics of canine visceral leishmaniasis (CVL) transmission were evaluated for 2 years, before beginning the screening-culling intervention. The comparative morbidity index (CMI) was used to stratify areas with the greatest risk of CVL, and the spatial distribution of human and canine VL cases was compared using univariate and bivariate K-functions. Human cases conglomerated in three neighborhoods. Spatial clusters were detected for CVL in 1998, 2000, and 2001, but not in 1999, when greater spatial dispersion occurred. The screening and culling intervention reduced the number of human VL cases and decreased the incidence of CVL, mainly in neighborhoods with a high CMI. The systematic euthanasia of seropositive dogs was shown to be an effective control action of the Program for Control of Visceral Leishmaniasis (PCLV) in Brazil. The fundamental role of domestic dogs in the epidemiological chain of VL was reaffirmed.

Sero-prevalence of visceral leishmaniasis and its associated factors among asymptomatic individuals visiting Denan health center, southeastern Ethiopia

BackgroundIn the Somali region of Ethiopia, visceral leishmaniasis (VL) is a public health concern. However, VL epidemiology and sand fly vectors have not been well studied in various areas of the regional state, including Denan district. Therefore, this study was conducted to determine the sero-prevalence, associated factors, and distribution of sand fly vectors of VL in Denan district, south-eastern Ethiopia.MethodsA facility-based cross-sectional study was conducted from April to September 2021 among VL patients with classic signs and symptoms visiting Denan Health Center in south-eastern Ethiopia. Using a convenience sampling method, 187 blood samples were collected from individuals who visited Denan Health Center during the study period. Blood samples were subjected to Direct Agglutination Test for the detection of antibodies to VL. A pre-tested structured questionnaire was also used to gather information on risk factors and other characteristics of knowledge and attitude assessment. Sand flies were also collected from indoor, peri-domestic, mixed forest, and termite mounds using light and sticky traps to determine the fauna and abundance.ResultsThe overall sero-prevalence rate was 9.63% (18/187). The sero-prevalence was significantly associated with outdoor sleeping (OR = 2.82), the presence of damp floors (OR = 7.76), and sleeping outdoor near animals (OR = 3.22). Around 53.48% of the study participants had previously heard about VL. Study participants practiced different VL control methods, including bed nets (42%), insecticide spraying (32%), smoking plant parts (14%), and environmental cleaning (8%). In total, 823 sand fly specimens, comprising 12 species in two genera (Phlebotomus and Sergentomyia), were trapped and identified. The most abundant species was Sergentomyia clydei (50.18%), followed by Phlebotomus orientalis (11.42%). Also, a higher proportion of P. orientalis was found in termite mounds (65.43%), followed by mixed forest (37.8%) and peri-domestic (20.83%) habitats.ConclusionThe study demonstrated a 9.63% sero-positivity of VL and a remarkable gap in knowledge, attitude, and practices towards VL. P. orientalis was also detected, which could be a probable vector in this area. Thus, public education should be prioritized to improve the community’s awareness of VL and its public health impact. In addition, detailed epidemiological and entomological studies are recommended.

Reemergence of Visceral Leishmaniasis in Henan Province, China.

Visceral leishmaniasis (VL) was widely prevalent in Henan Province in the 1950s. Through active efforts by the government, there were no local cases reported from 1984 to 2015. In 2016, local VL cases reoccurred, and there was an increasing trend of VL cases in Henan Province. To provide a scientific control of VL, an investigation was conducted in Henan Province from 2016 to 2021. The data from VL cases were obtained from the Disease Surveillance Reporting System of the Chinese Center for Disease Control and Prevention. The rK39 immunochromatographic test (ICT) and PCR assay were performed among high-risk residents and all dogs in the patients' village. ITS1 was amplified, sequenced, and subjected to phylogenetic analyses. A total of 47 VL cases were reported in Henan Province during 2016-2021. Of the cases, 35 were local, and they were distributed in Zhengzhou, Luoyang, and Anyang. The annual average incidence was 0.008/100,000, showing an upward trend year by year (χ2 = 3.987, p = 0.046). Their ages ranged from 7 months to 71 years, with 44.68% (21/47) in the age group of 0-3 years and 46.81% (22/47) in the age group ≥15 years. The cases occurred throughout the year. The high-risk populations were infants and young children (age ≤3), accounting for 51.06% (24/47), followed by farmers at 36.17% (17/47). The ratio of males to females was 2.13:1. The positive rates of rK39 ICT and PCR were 0.35% (4/1130) and 0.21% (1/468) in the residents. The positive rates of rK39 ICT and PCR were 18.79% (440/2342) and 14.92% (139/929) in the dogs. The ITS1 amplification products in the patients and positive dogs were sequenced. The homology between the target sequence and Leishmania infantum was more than 98%. The phylogenetic analysis indicated that the patients and the positive dogs were infected by the same type of Leishmania, which was consistent with the strains in the hilly endemic areas in China. This paper showed that patients and domestic dogs were infected by the same type of L. infantum and that the positive rate in dogs was relatively high in Henan Province. Because the measures of patient treatment and culling of infected dogs were not effective in reducing VL incidence in Henan Province, it is urgent to develop new approaches for the control of VL, such as wearing insecticide-impregnated collars on dogs, treating the positive dogs, spraying insecticide for sandflies control, and improving residents' self-protection awareness to prevent the further spread of VL in Henan Province.

Immunotherapy and immunochemotherapy in combating visceral leishmaniasis.

Visceral leishmaniasis (VL), a vector-borne disease, is caused by an obligate intramacrophage, kinetoplastid protozoan parasite of the genus Leishmania. Globally, VL is construed of diversity and complexity concerned with high fatality in tropics, subtropics, and Mediterranean regions with ~50,000-90,000 new cases annually. Factors such as the unavailability of licensed vaccine(s), insubstantial measures to control vectors, and unrestrained surge of drug-resistant parasites and HIV-VL co-infections lead to difficulty in VL treatment and control. Furthermore, VL treatment, which encompasses several problems including limited efficacy, emanation of drug-resistant parasites, exorbitant therapy, and exigency of hospitalization until the completion of treatment, further exacerbates disease severity. Therefore, there is an urgent need for the development of safe and efficacious therapies to control and eliminate this devastating disease. In such a scenario, biotherapy/immunotherapy against VL can become an alternative strategy with limited side effects and no or nominal chance of drug resistance. An extensive understanding of pathogenesis and immunological events that ensue during VL infection is vital for the development of immunotherapeutic strategies against VL. Immunotherapy alone or in combination with standard anti-leishmanial chemotherapeutic agents (immunochemotherapy) has shown better therapeutic outcomes in preclinical studies. This review extensively addresses VL treatment with an emphasis on immunotherapy or immunochemotherapeutic strategies to improve therapeutic outcomes as an alternative to conventional chemotherapy.

Spatio-temporal relative risks and priority areas for visceral leishmaniasis control in Brazil, between 2001 and 2020

Visceral leishmaniasis (VL) is a pressing public health problem in Brazil. The proper implementation of disease control programs in priority areas is a challenge for healthcare managers. The present study aimed to analyze the spatio-temporal distribution and identify high risk areas of VL occurrence in the Brazilian territory. We analyzed data regarding new cases with confirmed diagnosis of VL in Brazilian municipalities, from 2001 to 2020, extracted from the Brazilian Information System for Notifiable Diseases. The Local Index of Spatial Autocorrelation (LISA) was used to identify contiguous areas with high incidence rates in different periods of the temporal series. Clusters of high spatio-temporal relative risks were identified using the scan statistics. The accumulated incidence rate in the analyzed period was 33.53 cases per 100,000 inhabitants. The number of municipalities that reported cases showed an upward trend from 2001 onward, although there was a decrease in 2019 and 2020. According to LISA, the number of municipalities considered a priority increased in Brazil and in most states. Priority municipalities were predominantly concentrated in the states of Tocantins, Maranhão, Piauí, and Mato Grosso do Sul, in addition to more specific areas of Pará, Ceará, Piauí, Alagoas, Pernambuco, Bahia, São Paulo, Minas Gerais, and Roraima. The spatio-temporal clusters of high-risk areas varied throughout the time series and were relatively higher in the North and Northeast regions. Recent high-risk areas were found in Roraima and municipalities in northeastern states. VL expanded territorially in Brazil in the 21st century. However, there is still a considerable spatial concentration of cases. The areas identified in the present study should be prioritized for disease control actions.

Patterns and drivers of Human Visceral Leishmaniasis in Pernambuco (Brazil) from 2007 to 2018.

Visceral leishmaniasis (VL) is the second most common protozoosis that affects people around the world. The aim of this study is to understand how environmental and socioeconomic factors, as well as VL control and surveillance interventions, influence the spread and detection of VL cases in Pernambuco state (Brazil). A novel model was developed to analyze cases of VL between 2007 and 2018, enabling the quantification of the association of these variables with two processes: the probability of "invasion" (emergence of new cases) at municipalities by VL, and the probability of detecting cases not reported in municipalities that have already been invaded. Pernambuco state identified 1,410 cases of VL between 2007 and 2018, with an average of 128 cases per year and average incidence of 1.28/100 thousand people. These cases were distributed in 77.1% (142/184) of the municipalities, and 54.8% (773/1,410) of them were autochthonous. Our model reveals that the proportion of agriculture was positively associated with VL invasion probability. We also find that municipalities that are closer to notification centers and/or that have received technical training and support tend to have higher detection rates of VL cases. Taken together, these results suggest that a municipality with almost no agriculture and that received technical training, located close to a notification center, is unlikely to be invaded if no cases have ever been detected. On the other hand, a municipality that is far from the notification center, with no technical training, with a large agricultural area might have already been invaded but the surveillance system might have routinely failed to detect VL cases due to low detection probability. By disentangling the processes of invasion and detection, we were able to generate insights that are likely to be useful for the strategic allocation of VL prevention and control interventions.

Computer Vision in Automatic Visceral Leishmaniasis Diagnosis: a Survey

Visceral Leishmaniasis (VL) is a neglected disease that affects 1 billion people in tropical and subtropical countries. In Brazil, VL causes about 3,500 cases/year. Although this disease is lethal when left untreated, the number of cases is increasing. Thus, it is necessary to study current and safety technologies for VL diagnosis, treatment, and control. Specialized laboratories carry out the LV diagnosis, and this step has great automation power through automatic methods based on computer vision to aid in diagnosis. This work aims to present state-of-the-art research on computer vision techniques to detect VL in humans and provide a theoretical basis for developing computational systems to aid in diagnosing VL. This work's contributions are finding the methodologies and algorithms used in VL automatic detection and listing the gaps in developing those systems. As a result, we find out the lack of image databases and the use of deep learning techniques is still scarce. We conclude that methodologies that use the segmentation procedure perform better in terms of accuracy and that it is possible to develop a CAD system to help diagnose VL in humans.

Forty years (1980-2019) of visceral leishmaniasis in Nepal: trends and elimination challenges.

Visceral leishmaniasis (VL) is an important re-emerging neglected tropical disease associated with poverty. Despite the elimination initiative started in 2005, VL cases have been expanding into geographic areas in Nepal. The present study aims at exploring the trends of VL from 1980 to 2019. This retrospective analysis covers 40 y of VL cases reported by the Epidemiology Diseases Control Division, Nepal. Subgroup analyses for annual incidence were performed by age, sex, seasons, districts and provinces, and VL cases were visualized on in-country maps. A total of 34 564 cases and 584 deaths of VL were reported during 1980-2019. VL persistently increased until 2006 and was reported from all seven provinces of the country. The highest number of confirmed cases (n=2229) was reported in 2003 and the lowest (n=60) in 1983. VL cases expanded from 12 to 23 endemic districts. The key components of the VL elimination program are early diagnosis; enhanced surveillance; integrated vector management; social mobilization; research and treatment. Expansion of VL towards the hilly and mountain regions of Nepal has posed challenges to the elimination program. Urgent VL control measures are required to achieve the elimination goals.