SYSTEMATIC REVIEW OF LEISHMANIASIS IN PAKISTAN: EVALUATING SPATIAL DISTRIBUTION AND RISK FACTORS.

Both cutaneous (zoonotic cutaneous leishmaniasis [ZCL] and anthroponotic cutaneous leishmaniasis [ACL]) and visceral leishmaniasis (VL) are prevalent in Pakistan, although the cutaneous form is comparatively more widespread. The present study aimed to spatially map different forms of leishmaniasis in Pakistan. In addition, the risk for acquiring leishmaniasis was assessed in different locations of the country. Previously published literature on leishmaniasis distribution and associated risk factors in Pakistan was obtained from PubMed/NCBI and GoogleScholar using specific keywords. Further, 50 articles that focused on geographical distribution and risk factors of the disease in Pakistan were obtained and systematically reviewed. Data regarding location (used in ArcGIS for spatial analysis), number of cases, and risk factors were identified. The present study revealed a high burden of cutaneous leishmaniasis in the northern and western foci of Pakistan. Leishmania major, chiefly a causative agent of ZCL, was observed to be prevalent in the arid and semi-arid climatic zones of the country with elevations between 45 and 2,837 m (maximum number at low elevation). Leishmania tropica cases, associated with ACL, were recorded at elevations ranging from 551 to 2,837 m (majority cases at high elevation). Visceral leishmaniasis (VL) (reportedly caused by Leishmania infantum) was sporadically distributed in the northern areas at elevations 1,432-2,873 m. For VL, particularly, mountainous communities, farming communities, and the presence of dogs were the most commonly reported risk factors. On the other hand, poor preventive measures, migration, presence of domesticated animals, presence of cattle dung, living in mud houses, and outdoor sleeping habits were the principal risk factors associated with cutaneous leishmaniasis (CL). This investigation can guide the health experts and medical entomologists toward targeted and cost-effective surveillance and control of leishmaniasis in Pakistan.

Estimating human leishmaniasis burden in Spain using the capture-recapture method, 2016-2017.

Leishmaniasis is endemic and a mandatory reporting disease in Spain since 1982. However, between 1996 and 2014, surveillance on public health was decentralized and only some autonomous regions monitored the disease. The aim of this study is to estimate the incidence of leishmaniasis and to evaluate the extent of underreporting in Spain. A capture-recapture (CRC) study was conducted to calculate the incidence of human leishmaniasis using reports from the National Surveillance Network (RENAVE) and the Hospital Discharge Records of the National Health System (CMBD) for 2016 and 2017. During the study period, 802 cases were reported to RENAVE and there were 1,149 incident hospitalizations related to leishmaniasis. The estimated incidence rates through the CRC study were 0.79 per 100,000 inhabitants for visceral leishmaniasis (VL), 0.88 (cutaneous leishmaniasis (CL)) and 0.12 (mucocutaneous leishmaniasis (MCL)) in 2016 and 0.86 (VL), 1.04 (CL) and 0.12 (MCL) in 2017. An underreporting of 14.7-20.2% for VL and 50.4-55.1% for CL was found. The CRC method has helped us to assess the sensitivity and representativeness of leishmaniasis surveillance in Spain, being a useful tool to assess whether the generalization of leishmaniasis surveillance throughout the Spanish territory achieves a reduction in underreporting.

Real-Time Fluorimetry Loop-Mediated Isothermal Amplification for Diagnosis of Leishmaniasis and as a Tool for Assessment of Cure for Post-Kala-Azar Dermal Leishmaniasis.

Despite the dwindling number of visceral leishmaniasis (VL) cases in India, there is an urgent need for early and unequivocal diagnostics for controlling and preventing the reemergence of VL. Post-kala-azar dermal leishmaniasis (PKDL), a dermal sequela of VL, serves as a reservoir of the parasite. Diagnosis of PKDL, especially the macular variant, is challenging and poses impediment toward attainment of VL elimination. In this study, a real-time fluorimetry loop-mediated isothermal amplification (RealAmp) assay has been established for the detection of different clinical manifestations of leishmaniasis. The study included 150 leishmaniasis patients (25 VL, 25 cutaneous leishmaniasis [CL], and 100-PKDL) along with 120 controls. The assay demonstrated sensitivity of 100% (95% CI: 86.68-100) for diagnosis of VL and PKDL (95% CI: 79.61-100) and 96% (95% CI: 86.68-100) for CL with 100% specificity. Moreover, considering the cardinal role of PKDL, diagnosis using minimally invasive slit aspirate was explored, which demonstrated remarkable sensitivity of 96% (95% CI: 87.64-98.47). As a test of cure for PKDL, RealAmp successfully detected parasite in two of posttreatment cases who later reported relapse on follow-up. Also, direct sample lysis using slit aspirate was attempted in a small group that yielded sensitivity of 89% (95% CI: 67.20-96.90). RealAmp depicted excellent diagnostic accuracy in the diagnosis of leishmaniasis in concordance with the established SYBR Green I-based (Molecular Probes, Eugene, OR) visual loop-mediated isothermal amplification (LAMP) and the reference comparator real-time PCR. The study endorsed the employment of LAMP either as visual-LAMP or RealAmp for an accurate and expeditious diagnosis of PKDL and as a tool for assessment of cure.

Comparison of acute phase proteins in different clinical classification systems for canine leishmaniosis.

The main objective of the present study was to evaluate the acute phase protein (APP) concentrations that dogs naturally infected with Leishmania infantum show in different clinical stages of disease staged according to the Leishvet and CLWG classifications. In addition, these classifications are compared with the groups based on APP recommendations published recently. Medical records of 458 dogs with leishmaniosis whose samples were submitted to our laboratory for clinical pathology evaluation were reviewed and 77 cases met the inclusion criteria. All dogs were classified according to the CLWG system and the majority of the dogs (33.8%) were classified in stage D. Although some dogs (41.6%) could not be classified by the Leishvet system since it includes only dogs with clinical disease, most of the classified dogs (27.3%) were at Leishvet stage II. According to the APP classification, the majority of dogs (32.5%) were classified in stage 3a. Dogs in the more advanced stages of Leishvet and CWLG classifications had significant increases in serum ferritin and C-reactive protein (CRP) and decrease in Paraoxonase 1 (PON1). These findings indicate that APPs show more significant changes in the more advanced stages of Leishvet and CWLG classifications corresponding with more severe cases of canine leishmaniosis.

Spatial analysis of leishmaniasis in Brazil: a systematized review.

The aim of this study was to perform a systematic review of scientific papers that used spatial analysis tools in cases of leishmaniasis, in Brazil. The search for articles was carried out in PubMed, SciELO, Scopus and Web of Science databases. The keywords used in the identification of the articles were Thematic map AND Leishmaniasis, Spatial analysis AND Leishmaniasis, and Geoprocessing AND Leishmaniasis, in English language. A total of 360 articles were found, and 11 of them were analyzed after screening by title and abstract as well as reading of the full articles. The States studied were Sao Paulo, Acre, Maranhao, Piaui, Minas Gerais, Parana and Tocantins. Cutaneous leishmaniasis occurred predominantly in rural areas, with clusters in forest reserve regions or modified forest areas. Conversely, visceral leishmaniasis mainly occurred in peripheral and central urban areas associated with poorer environments and urban infrastructure, including worse sanitation. We conclude that the spatial distribution of leishmaniasis is closely related to the living environment of the risk population. The analyzed articles associated geospatial data with some risk factors for the disease, pointing out the locations where most cases occur, creating a relevant source to define control strategies.

Leishmania infections: Molecular targets and diagnosis.

Progress in the diagnosis of leishmaniases depends on the development of effective methods and the discovery of suitable biomarkers. We propose firstly an update classification of Leishmania species and their synonymies. We demonstrate a global map highlighting the geography of known endemic Leishmania species pathogenic to humans. We summarize a complete list of techniques currently in use and discuss their advantages and limitations. The available data highlights the benefits of molecular markers in terms of their sensitivity and specificity to quantify variation from the subgeneric level to species complexes, (sub) species within complexes, and individual populations and infection foci. Each DNA-based detection method is supplied with a comprehensive description of markers and primers and proposal for a classification based on the role of each target and primer in the detection, identification and quantification of leishmaniasis infection. We outline a genome-wide map of genes informative for diagnosis that have been used for Leishmania genotyping. Furthermore, we propose a classification method based on the suitability of well-studied molecular markers for typing the 21 known Leishmania species pathogenic to humans. This can be applied to newly discovered species and to hybrid strains originating from inter-species crosses. Developing more effective and sensitive diagnostic methods and biomarkers is vital for enhancing Leishmania infection control programs.

Diagnosis & management of leishmania/HIV co-infection.

Leishmaniasis, a globally prevalent parasitic disease occurs in three forms viz., visceral, cutaneous and mucocutaneous, transmitted by the bite of infected female Phlebotomus sandflies. Visceral leishmaniasis (VL) has 100 per cent fatality rate, if left untreated. India has the largest burden of this disease. HIV infection is also increasing worldwide and several reports indicate rising trend of VL/ HIV co-infection, modifying the traditional anthroponotic pattern of VL transmission. Both VL and HIV tend to lower the cell mediated immunity (CMI) resulting in poor drug response and opportunistic infections involving gastrointestinal, cutaneous, respiratory tract and central nervous system (CNS) may occur. Diagnosis of such co-infected cases is quite difficult. However, newer tests like nested PCR, rk39 immunochromatographic test etc., can be of help. Response to different antileishmanial drugs like sodium antimony gluconate (SAG), amphotericin B is far from satisfactory. However, a new oral drug miltefosine has been found to be promising. Highly active antiretroviral therapy (HAART) need to be given for management of HIV infection along with treatment of other opportunistic infections.

Leishmaniasis: early diagnosis is key.

A patient presents with nasal congestion, a history of nosebleed, and painful lesions on his body and in his mouth. What questions should you ask to ensure that you make an accurate diagnosis?

A histological classification of mucocutaneous leishmaniasis in Brazil and its clinical evaluation.

Biopsies of skin and mucosal lesions were made on 60 well documented Brazilian patients with untreated cutaneous or mucocutaneous leishmaniasis, whose response to treatment was subsequently evaluated in 38 cases. The biopsies were examined with a view to classification after correlation with clinical and immunological findings. Although there was no simple or unified spectrum, five histological groups were defined and found to have some clinico-prognostic significance. In two groups the cases were all cutaneous with a relatively good prognosis. In another two groups they were evolving as mucocutaneous with a poor prognosis. The fifth group showed mixed characteristics with a tendency to relapse. There was no strong correlation with serum antibodies or Montenegro skin test, which were usually positive, or with parasite load, which was always low. The tissue response was distinguished from that in oriental sore by the degree of connective tissue involvement in all groups. It was the primary response in two groups, and subsidiary to a mono-nuclear response in the others. It suggested damage due to extra-cellular parasites or immune complexes. It did not correlate with the distinction between cutaneous and mucocutaneous disease. The single, most favourable, prognostic feature in either the cellular or connective tissue component was necrosis with a reactive response.

[Leishmaniasis and human immunodeficiency virus: an emerging co-infection?]. / Leishmaniose et virus de l'immunodéficience humaine: une co-infection en émergence?

Although not considered as indicative of AIDS, leishmaniasis presents a number of epidemiologic and clinical features that promote opportunistic infection in HIV patients. Accurate assessment of the incidence of this type of co-infection is difficult due to underestimation in endemic areas such as Africa and Asia. In these areas the WHO estimates that 2 to 9 p. 100 of HIV patients will develop leishmaniasis/HIV co-infection which could become a major concern. The characteristics of this co-infection have been documented. It is observed in adults between 20 and 40 years of age with a strong male sex bias. The visceral form is most frequent. Manifestations are similar to those observed in immunocompetent subjects but with the possibility of asymptomatic and low-grade forms (10 p. 100) and unusual locations suggesting multiorgan spreading in absence of host immune response. In addition to the time-tested standard procedures for diagnosis of parasitic disease, new serologic tests and genomic amplification are now available. Pentavalent antimonials have long been considered as the treatment of choice but they are not always effective and can have untoward effects. Amphotericine B especially in the liposomal form is a good alternative. The particularly high incidence of recurrence suggests that follow-up may be indicated but the modalities of prophylaxis have yet to be defined.

[Hansenoid anergic leishmaniasis]. / Leishmaniose anérgica hansenóide.

The A. repport an anomalous form of tegumentar leishmaniasis, the to called "leishmaniasis cutis diffusa". The A. call attention to the rarity of this type in the neotropical region, where only 38 cases were registered in the medical literature. The A. call attention to the anergy and presence of nodular lesions, which are importtants elements, resembling the lepromatous' leprosy. Because of this symptoms, present in all cases, the A. propose the new denomination of Hansenoide Anergic Leishmaniasis of this type of the disease.

[Cutaneous and muucocutaneous leishmaniasis. New findings on the subject]. / Leishmaniasis cutánea y cutáneo-mucosa. Nuevos aportes sobre el tema.

The authors have carried a work in which they studied the Leishmaniasis of the skin and their cutaneo-mucosal manifestations, marking on the fact that both are caused by the same agent. They considered also that the visceral Leishmaniasis would be occasioned by the same parasite but in this latter case, it can occur only in anergic people. Finally, they made a clinical and pathologic classification of the cutaneous Leishmania and cutaneo-mucosal Leishmania in: 1. A primary period with 3 histologic manifestations very well known. 2. A period of latency which is variable in time of duration; some times is permanently with parasites in quiescent state in the cells of the reticulous endothelial system. 3. A period of reactivation with cutaneo-mucosal lesions, which shows 3 anatomic and clinic periods: erythematous edematous, granulomatous-proliferative and granulose-necrotic with very important destructions in oropharynx.

Leishmaniasis: Opciones terapéuticas en la población pediátrica / Leishmaniasis: Therapeutic options in the pediatric population

Resumen La leishmaniasis es una enfermedad parasitaria crónica endémica en muchas partes del mundo. La variabilidad de cepas, su clínica y respuesta a tratamiento ha hecho que se clasifique en dos grandes grupos: la leishmaniasis del Nuevo Mundo y la del Viejo Mundo. Según esto, varían las recomendaciones respecto a manejo y seguimiento. En esta revisión se hace énfasis a la leishmaniasis de nuestro medio, revisando opciones terapéuticas y posibilidades principalmente en la población pediátrica.

Abstract Leishmaniasis is a chronic parasitic disease endemic in many parts of the world. The variability of strains, their clinic and response to treatment has led to their classification into two major groups: New World leishmaniasis and Old World leishmaniasis. According to this, the recommendations regarding management and follow-up vary. In this review, emphasis is placed on leishmaniasis in our environment, reviewing therapeutic options and possibilities mainly in the pediatric population.

Clinical pleiomorphism in human leishmaniases, with special mention of asymptomatic infection.

This review gives an update of current knowledge on the clinical pleiomorphism of Leishmania, with a special emphasis on the case of asymptomatic carriage. The first part describes the numerous unusual expressions of the disease that occur besides the classic (visceral, cutaneous, and mucocutaneous) forms of leishmaniases. The second part deals with progress in the understanding of disease outcome in humans, and the possible future approaches to improve our knowledge in the field. The third part highlights the role of the too often neglected asymptomatic carrier compartment. This group could be key to understanding infraspecific differences in virulence and pathogenicity of the parasite, as well as identifying the genetic determinants involved in the expression of the disease.