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1.
Malar J ; 19(1): 385, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33129327

RESUMO

Malaria risk and endemicity is often associated with the nature of human habitation and living environment. The disappearance of malaria from regions where it had been endemic for centuries, such as coastal areas of southern England, has been attributed, at least in part, to improvement in the quality of housing. Moreover, indigenous malaria transmission ceased throughout England without the necessity to eliminate the vector mosquitoes. The principles of malaria transmission, as formulated following the thinking of the pioneers of malaria epidemiology, Ronald Ross and George Macdonald, show how this may happen. Malaria ceases to be sustainable where its reproduction number, R0, the number of new cases generated on average for each existing case of malaria, falls below 1. In the terms of a Ross/Macdonald analysis the reduced contact between humans and blood-feeding mosquitoes that is achieved through housing that is secure against mosquito entry can have a powerful effect in reducing malaria R0. The island of Sri Lanka, where malaria had been endemic probably for centuries previously, has reported no indigenous cases of malaria since 2012. The disappearance of malaria from Sri Lanka followed an effective attack upon malaria transmission by the Sri Lanka Anti Malaria Campaign. The targeted and enhanced efforts of this campaign launched in 1999, drove the malaria R0 below 1 for most of the period up to 2012, leading to a nearly continuous decline in malaria cases until their extinction. The decades leading up to the launch of these efforts were ones of general improvement of living environment and notably in the quality of housing stock. Studies in the late 1980s had shown that quality of housing in a highly malarious district of Sri Lanka was a strong determinant of malaria risk. Through its effects on malaria R0, improved housing is likely to have facilitated the malaria control and cessation of indigenous malaria transmission in Sri Lanka and that it will help reduce the risk of the re-introduction of malaria to the island.

2.
Case Rep Dermatol Med ; 2020: 8899586, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32904486

RESUMO

This article describes an atypical case of post-kala-azar dermal leishmaniasis associated with complications due to delayed diagnosis and poor case management. The grave consequences of the prolonged disease process that continued for over 2 decades with eventual healing included facial disfigurement, visual impairment, and mental distress both to the patient and the family. The persistent infection within the skin over a lengthy period with likely increased risk of infection spread in the community highlights its potential negative impact on the ongoing leishmaniasis elimination program in the Indian subcontinent. Bhutan is a member of the leishmaniasis elimination network in Asia, and the government continues to invest in maintenance of the national healthcare system. The case study reveals the gaps in the healthcare system with hardships faced by a patient to access quality healthcare and poor patient outcome used as proxy indicators. It also points to the need to enhance access to healthcare to ensure early diagnosis and effective treatment for leishmaniasis patients including those who live in remote areas, in order to achieve the planned disease elimination targets. It also points towards the key challenges faced by a resource poor nation such as Bhutan in achieving universal health coverage and reaching the set goals for disease elimination. The findings underscore the need for a careful review of the national health care system and to address the deficiencies.

3.
Malar J ; 19(1): 342, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958025

RESUMO

BACKGROUND: Sri Lanka was certified as a malaria-free nation in 2016; however, imported malaria cases continue to be reported. Evidence-based information on the genetic structure/diversity of the parasite populations is useful to understand the population history, assess the trends in transmission patterns, as well as to predict threatening phenotypes that may be introduced and spread in parasite populations disrupting elimination programmes. This study used a previously developed Plasmodium vivax single nucleotide polymorphism (SNP) barcode to evaluate the population dynamics of P. vivax parasite isolates from Sri Lanka and to assess the ability of the SNP barcode for tracking the parasites to its origin. METHODS: A total of 51 P. vivax samples collected during 2005-2011, mainly from three provinces of the country, were genotyped for 40 previously identified P. vivax SNPs using a high-resolution melting (HRM), single-nucleotide barcode method. Minor allele frequencies, linkage disequilibrium, pair-wise FST values, and complexity of infection (COI) were evaluated to determine the genetic diversity. Structure analysis was carried out using STRUCTURE software (Version 2.3.4) and SNP barcode was used to identify the genetic diversity of the local parasite populations collected from different years. Principal component analysis (PCA) was used to determine the clustering according to global geographic regions. RESULTS: The proportion of multi-clone infections was significantly higher in isolates collected during an infection outbreak in year 2007. The minor allele frequencies of the SNPs changed dramatically from year to year. Significant linkage was observed in sample sub-sets from years 2005 and 2007. The majority of the isolates from 2007 consisted of at least two genetically distinct parasite strains. The overall percentage of multi-clone infections for the entire parasite sample was 39.21%. Analysis using STRUCTURE software (Version 2.3.4) revealed the high genetic diversity of the sample sub-set from year 2007. In-silico analysis of these data with those available from other global geographical regions using PCA showed distinct clustering of parasite isolates according to geography, demonstrating the usefulness of the barcode in determining an isolate to be indigenous. CONCLUSIONS: Plasmodium vivax parasite isolates collected during a disease outbreak in year 2007 were more genetically diverse compared to those collected from other years. In-silico analysis using the 40 SNP barcode is a useful tool to track the origin of an isolate of uncertain origin, especially to differentiate indigenous from imported cases. However, an extended barcode with more SNPs may be needed to distinguish highly clonal populations within the country.

4.
Parasit Vectors ; 13(1): 246, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404115

RESUMO

BACKGROUND: Leishmania donovani-induced and sand fly-transmitted leishmaniasis is a growing health problem in Sri Lanka. Limited knowledge on biological and behavioral characteristics of probable vector Phlebotomus argentipes hinders disease control. Here, insecticide susceptibility patterns of P. argentipes were investigated with exploration of probable underlying resistance mechanisms. METHODS: Adult sand flies were collected using standard cattle baited net traps and CDC light traps from selected sites in four districts. Adult F1 progeny of P. argentipes were exposed to different concentrations of DDT, malathion, deltamethrin and propoxur using WHO susceptibility bioassay kits. Post-1-h knockdown and post-24-h mortality were recorded and analyzed. Metabolic enzyme activity and the sensitivity of the acetylcholinesterase target-site were determined by biochemical assays using wild-caught flies. Extracted fly DNA samples were tested for the presence of knockdown-resistance (kdr) type mutations. RESULTS: The LC100 values for DDT, malathion, propoxur and deltamethrin were 0.8-1.5%, 0.9-2.0%, 0.017-0.03% and 0.007% respectively. Insecticide-susceptibility levels were higher than the discriminating dosages established for Aedes mosquitoes, except for malathion. The lowest susceptibility levels (except for deltamethrin) were detected in the Mamadala population, whereas the highest levels were detected in the Mirigama population. The percentage of knocked-down sand flies was < 75% at any tested concentration, including those, which exhibited 100% mortality after 24 h. Elevated activity levels of glutathione S-transferase (3%, 7%, 12.5% and 14%) and esterase (2%, 5%, 5.5% and 6.5%) were detected in flies that originated from Mirigama, Pannala, Thalawa and Mamadala respectively, while monooxygenase quantities remained below the cut-off level. Ten to 34.5% of flies were heterozygous for acetylcholinesterases target-site insensitivity, associated with organophosphate and carbamate resistance. Pyrethroid-resistance-associated L1014F kdr-type mutation in the voltage gated sodium channel gene was detected in 30/53 flies. CONCLUSIONS: Populations of P. argentipes in Sri Lanka are largely susceptible to common insecticides, except for malathion (used extensively in the past for malaria control). Their insecticide susceptibility appears negatively associated with past malaria endemicity of the study sites, with signs of early insecticide tolerance. Presence of insecticide target site insensitivity in a notable proportion of flies and enhanced insecticide metabolizing enzyme activities imply potential future challenges for leishmaniasis control, with a call for urgent proactive measures for its containment.

5.
Int J Anal Chem ; 2020: 6129132, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32231701

RESUMO

Protein quantification is often an essential step in any research field that involves proteins. Although the standard Lowry assay and its modifications are most abundantly used in protein quantification, the existing methods are rigid or often demonstrate nonlinearity between protein concentration and color intensity. A method for fast and accurate qualitative and/or quantitative determination of total soluble/insoluble proteins or micro-well plate immobilized proteins isolated from Leishmania parasites in microvolumes was described in the current study. Improvements in cost-effective techniques are necessary to increase the research outputs in resource-limited settings. This method is a modification to the established Lowry assay for protein quantification. Concentrations of unknown samples were calculated using a standard curve prepared using a standard series of bovine serum albumin (BSA). The optimized reagents were 2 N NaOH (sodium hydroxide), 2% Na2CO3 (sodium carbonate), 1% CuSO4 (copper sulfate), 2% KNaC4H4O6 (potassium sodium tartrate), and 2 N Folin and Ciocalteu's phenol. This modified protein assay was sensitive for quantifying Leishmania proteins in a total crude extract or in a soluble fraction within the approximate range of 10-500 µg/ml (1-50 µg/assay) and showed a linearity between color intensity and concentration of the protein. This is an easier, fast, and accurate method for quantifying proteins with microvolumes in a cost-effective manner for routine use in research laboratories in resource-limited settings.

6.
Parasitol Int ; 75: 102047, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31887394

RESUMO

Leishmania donovani, a protozoan parasite of family Trypanosomatidae, causes fatal visceral leishmaniasis (VL) in the Indian subcontinent and Africa and cutaneous leishmaniasis (CL) in Sri Lanka. Another member of Trypanosomatidae, Leptomonas seymouri, resembling Leishmania was discovered recently to co-exist with L. donovani in the clinical samples from India and Sri Lanka and therefore, interfere with its investigations. We earlier described a method for selective elimination of such co-existing L. seymouri from clinical samples of VL exploiting the differential growth of the parasites at 37 °C in vitro. Here, we explored ways for a rapid discriminatory diagnosis using high resolution melting (HRM) curves to detect co-occurring L. seymouri with L. donovani in clinical samples. Initial attempt with kDNA-minicircle (mitochondrial DNA) based HRM did not display different Tm values between L. donovani and L. seymouri. Surprisingly, all of their minicircle sequences co-existed in similar clades in the dendrogram analysis, although the kDNA sequences are known for its species and strain specific variations among the Trypanosomatids. However, an HRM analysis that targets the HSP70 gene successfully recognized the presence of L. seymouri in the clinical isolates. This discovery will facilitate rapid diagnosis of L. seymouri and further investigations in to this elusive organism, including the clinico-pathological implications of its co-existence with L. donovani in patients.


Assuntos
Coinfecção/diagnóstico , Infecções por Euglenozoa/diagnóstico , Leishmania donovani/isolamento & purificação , Leishmaniose Visceral/diagnóstico , Trypanosomatina/isolamento & purificação , DNA de Cinetoplasto/análise
7.
Emerg Infect Dis ; 26(1): 1-10, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31855147

RESUMO

Leishmaniasis, a neglected tropical disease, is on the decline in South Asia. However, cases of cutaneous leishmaniasis have risen in Sri Lanka since 2001, and the lack of in-depth research on its epidemiologic characteristics hampers control efforts. We analyzed data collected from patients with cutaneous leishmaniasis in Sri Lanka during 2001-2018 to study temporal and geographic trends and identify and monitor disease hotspots. We noted a progression in case rates, including a sharp rise in 2018, showing temporal expansion of disease-prevalent areas and 2 persistent hotspots. The northern hotspot shifted and shrank over time, but the southern hotspot progressively expanded and remained spatially static. In addition, we noted regional incidence differences for age and sex. We provide evidence of temporally progressive and spatially expanding incidence of leishmaniasis in Sri Lanka with distinct geographic patterns and disease hotspots, signaling an urgent need for effective disease control interventions.

8.
J Trop Med ; 2019: 6475939, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428163

RESUMO

Cutaneous leishmaniasis caused by a genetic variant of L. donovani is being reported from Sri Lanka since year 2001. Patients presented from different geographical locations (600 patients from North or South and a minority of cases from other foci, 2001-2013) were studied. Analysis revealed two different sociodemographic and clinical profiles of leishmaniasis in Northern and Southern Sri Lanka. Also, the same different profiles were present in these foci since the onset of the recent outbreak and had independently propagated within each focus over the time. A profile of 14 parameters identified in the Northern focus was further examined with regard to other locations. Northwestern (10/14) and Central parts (9/14) of the island were more similar to Northern focus (14/14). Infection would have originated in one focus and spread to other 2 in Northern Sri Lanka. Southern focus was different from and appeared older than all others (2/14). Western focus that accommodates a large transient population had a mixed picture of North and South features (4/14). Lesions in North showed a slow progression and a nonulcerative nature (128/185, 69.2%), while those in South showed a rapid progression and less nonulcerative lesions (193/415, 46.5%). Clinical analysis favoured a parasite aetiology (considerable strain differences) rather than a host aetiology (age, gender, or genetics). Both foci demonstrated a biannual seasonal variation since the onset of the epidemic. Two peaks were observed during the early and latter parts of the year. Furthermore, long-term existence and recent spatiotemporal expansion and detection of leishmaniasis in this country rather than a recent introduction and establishment were indicated by these findings. Vigorous antimalarial activities that existed in Sri Lanka until few decades ago, lack of professional awareness, and more recent military activities that brought human population in close contact with a sylvatic cycle would have played a role in silent propagation of Leishmania parasites and subsequent increment in human cases, respectively, in this country.

9.
Sci Rep ; 9(1): 9932, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31289323

RESUMO

Visceral leishmaniasis (VL) is one of the leading infectious diseases affecting developing countries. Colloidal gold-based diagnostic tests are rapid tools to detect blood/serum antibodies for VL diagnosis. Lack of uniformity in the performance of these tests in different endemic regions is a hurdle in early disease diagnosis. This study is designed to validate a serum-based dipstick test in eight centres of six countries, India, Nepal, Sri Lanka, Brazil, Ethiopia and Spain with archived and fresh sera from 1003 subjects. The dipstick detects antibodies against Leishmania donovani membrane antigens (LAg). The overall sensitivity and specificity of the test with 95% confidence intervals were found to be 97.10% and 93.44%, respectively. The test showed good sensitivity and specificity in the Indian subcontinent (>95%). In Brazil, Ethiopia, and Spain the sensitivity and specificity of the dipstick test (83.78-100% and 79.06-100%) were better as compared to the earlier reports of the performance of rK39 rapid test in these regions. Interestingly, less cross-reactivity was found with the cutaneous form of the disease in Spain, Brazil, and Sri Lanka demonstrating 91.58% specificity. This dipstick test can therefore be a useful tool for diagnosing VL from other symptomatically similar diseases and against cutaneous form of leishmaniasis.


Assuntos
Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Leishmania donovani/imunologia , Leishmaniose Visceral/sangue , Leishmaniose Visceral/diagnóstico , Proteínas de Protozoários/imunologia , Testes Sorológicos/métodos , Brasil/epidemiologia , Estudos de Casos e Controles , Etiópia/epidemiologia , Humanos , Índia/epidemiologia , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/parasitologia , Nepal/epidemiologia , Espanha/epidemiologia , Sri Lanka/epidemiologia
10.
J Trop Med ; 2019: 4538597, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31263501

RESUMO

Sri Lanka is a recent focus having Leishmania donovani induced cutaneous leishmaniasis (CL) as the main clinical entity. A separate clinical entity within profile of CL was described in this study. Laboratory confirmed cases of CL (n= 950, 2002-2014) were analysed. Most lesions showed known classical developmental stages of CL (CCL) observed in other CL endemic settings while few cases (13%, 122/950) showed atypical skin manifestations (ACL). Clinical, geographical, and treatment response patterns of ACL were different from those of CCL. ACL was mainly found among males (68.0%), in 21-40 year age group (51.6%), and reported delayed treatment seeking (23.5% vs 16.3% in CCL), more nonclassical onset (lesions other than acne form <1cm sized papules), (12.1 vs 2.7%, P<0.05.), more head and neck lesions (41.5%. vs 27.2%), more large lesions (>4cm), (18.6 vs 9.9%), and poor laboratory positivity rates (65.6% vs 88.2%) when compared to CCL. When compared to lesions reporting a typical onset, lesions reporting nonclassical onset were more likely to develop ACL later on (50.1% vs 10.7%). As compared to lesions on limbs, those on head and neck and trunk were more likely to be ACL (7.0%, 16.3%, and 22.8%, respectively, P<0.05). ACL features were not age or gender dependent. Highest proportion within ACL category (32.8%) and small proportion of CCL (10.1%) originated from less leishmaniasis prevalent areas (other regions) (P<0.05). North reported more ACL than South (15.9% vs 7.4%). A total of 95 CL cases with a significant travel history were further analyzed. Residents of other regions when acquired infection from North or South developed more ACL than residents in North or South (60.9% vs 15.9% and 42.9% vs 7.4% respectively). Patients in other regions when travelled to North developed more ACL than when they travelled to South (60.9%, 42.9%). ACL and CCL required an average of 18 doses over 16.7 months and 10 doses over 12 weeks, respectively, to achieve a complete clinical cure. Underlying host immunological factors, parasite strain variations and regional variations of both could be underlying etiologies. Established independent transmission within less leishmaniasis prevalent regions combined with an unusual clinical picture leading to poor clinical suspicion and low laboratory confirmation rate will pose potential difficulties in early case detection in these highly populated and commercialized areas. This in turn will further facilitate silent and high disease transmission.

11.
Biomed Res Int ; 2019: 4093603, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31111052

RESUMO

Sri Lanka reports a large epidemic of cutaneous leishmaniasis (CL) caused by an atypical L. donovani while regional leishmaniasis elimination drive aims at achieving its targets in 2020. Visceralization, mucotrophism, and CL associated poor treatment response were recently reported. Long-term clinico-epidemiological trends (2001-2013) in this focus were examined for the first time. Both constant and changing features were observed. Sociodemographic patient characteristics that differ significantly from those of country profile, microchanges within CL profile, spatial expansion, constant biannual seasonal variation, and nondependency of clinical profile on age or gender were evident. Classical CL remains the main clinical entity without clinical evidence for subsequent visceralization indicating presence of parasite strain variation. These observations make a scientific platform for disease control preferably timed based on seasonal variation and highlights the importance of periodic and continued surveillance of clinic-epidemiological and other characteristics.


Assuntos
Leishmania donovani/patogenicidade , Leishmaniose Cutânea/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Medula Óssea , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Leishmaniose Cutânea/parasitologia , Masculino , Pessoa de Meia-Idade , Estações do Ano , Pele , Sri Lanka/epidemiologia , Adulto Jovem
12.
Malar J ; 17(1): 473, 2018 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-30558622

RESUMO

BACKGROUND: Antibodies against the merozoite surface protein 1-19 (MSP1-19) and the apical membrane antigen 1 (AMA1) of the malaria parasite (Plasmodium vivax) are proven to be important in protection against clinical disease. Differences in the production/maintenance of antibodies may be due to many factors including host genetics. This paper discusses the association of 4 anti-malarial antibodies with selected host genetic markers. METHODS: Blood was collected from individuals (n = 242) with a history of malaria within past 15 years for DNA and serum. ELISA was carried out for serum to determine the concentration of anti-malarial antibodies MSP1-19 and AMA1 for both vivax and falciparum malaria. 170 SNPs related to malaria were genotyped. Associations between seropositivity, antibody levels and genetic, non-genetic factors were determined. RESULTS: Age ranged 13-74 years (mean age = 40.21 years). Majority were females. Over 90% individuals possessed either one or more type(s) of anti-malarial antibodies. Five SNPs were significantly associated with seropositivity. One SNP was associated with MSP1-19_Pv(rs739718); 4 SNPs with MSP1-19_Pf (rs6874639, rs2706379, rs2706381 and rs2075820) and1 with AMA1_Pv (rs2075820). Eleven and 7 genotypes (out of 15) were significantly associated with either presence or absence of antibodies. Three SNPs were found to be significantly associated with the antibody levels viz. rs17411697 with MSP1-19_Pv, rs2227491 with AMA1_Pv and rs229587 with AMA1_Pf. Linkage of the markers in the two groups was similar, but lower LOD scores were observed in seropositives compared to seronegatives. DISCUSSION AND CONCLUSIONS: The study suggests that several SNPs in the human genome that exist in Sri Lankan populations are significantly associated with anti-malarial antibodies, either with generation and/or maintenance of antibodies for longer periods, which can be due to either individual polymorphisms or most probably a combined effect of the markers.


Assuntos
Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/imunologia , Imunidade Humoral , Malária Falciparum/imunologia , Malária Vivax/imunologia , Proteínas de Membrana/imunologia , Proteína 1 de Superfície de Merozoito/imunologia , Polimorfismo Genético , Proteínas de Protozoários/imunologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Plasmodium falciparum/fisiologia , Plasmodium vivax/fisiologia , Sri Lanka , Adulto Jovem
13.
BMC Genomics ; 19(1): 843, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30486770

RESUMO

BACKGROUND: Leishmaniasis is a neglected tropical disease with diverse clinical phenotypes, determined by parasite, host and vector interactions. Despite the advances in molecular biology and the availability of more Leishmania genome references in recent years, the association between parasite species and distinct clinical phenotypes remains poorly understood. We present a genomic comparison of an atypical variant of Leishmania donovani from a South Asian focus, where it mostly causes cutaneous form of leishmaniasis. RESULTS: Clinical isolates from six cutaneous leishmaniasis patients (CL-SL); 2 of whom were poor responders to antimony (CL-PR), and two visceral leishmaniasis patients (VL-SL) were sequenced on an Illumina MiSeq platform. Chromosome aneuploidy was observed in both groups but was more frequent in CL-SL. 248 genes differed by 2 fold or more in copy number among the two groups. Genes involved in amino acid use (LdBPK_271940) and energy metabolism (LdBPK_271950), predominated the VL-SL group with the same distribution pattern reflected in gene tandem arrays. Genes encoding amastins were present in higher copy numbers in VL-SL and CL-PR as well as being among predicted pseudogenes in CL-SL. Both chromosome and SNP profiles showed CL-SL and VL-SL to form two distinct groups. While expected heterozygosity was much higher in VL-SL, SNP allele frequency patterns did not suggest potential recent recombination breakpoints. The SNP/indel profile obtained using the more recently generated PacBio sequence did not vary markedly from that based on the standard LdBPK282A1 reference. Several genes previously associated with resistance to antimonials were observed in higher copy numbers in the analysis of CL-PR. H-locus amplification was seen in one cutaneous isolate which however did not belong to the CL-PR group. CONCLUSIONS: The data presented suggests that intra species variations at chromosome and gene level are more likely to influence differences in tropism as well as response to treatment, and contributes to greater understanding of parasite molecular mechanisms underpinning these differences. These findings should be substantiated with a larger sample number and expression/functional studies.


Assuntos
Genoma , Leishmania donovani/genética , Leishmania donovani/patogenicidade , Aneuploidia , Gluconato de Antimônio e Sódio/farmacologia , Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Sequência de Bases , Cromossomos/genética , Dosagem de Genes , Ontologia Genética , Heterozigoto , Homozigoto , Humanos , Mutação INDEL/genética , Leishmania donovani/efeitos dos fármacos , Leishmania donovani/isolamento & purificação , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Fases de Leitura Aberta/genética , Filogenia , Polimorfismo de Nucleotídeo Único/genética , Virulência/efeitos dos fármacos , Virulência/genética
14.
Int J Dermatol ; 57(12): 1442-1446, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30246447

RESUMO

BACKGROUND: The quality of life in many patients is affected by skin lesions. Cutaneous leishmaniasis (CL), the commonest form of leishmaniasis, is no exception. In Sri Lanka, CL is an emerging parasitological condition with over 3,000 cases within the last decade. Lesions are often seen on exposed parts of the body which may cause social stigma, and hence a study was done to assess the changes in quality of life of CL patients. METHOD: A total of 294 patients (200 civilians and 94 army personnel) answered a previously validated Sinhala self-administered Dermatology Life Quality Index (DLQI) questionnaire and an interviewer-administered questionnaire. RESULTS: From the majority of the civilian population, 47% had no effect on their quality of life due to CL lesions, 33.5% were affected in a small way, 12.5% were affected moderately, 6.5% suffered in a large way, and 0.5% (one patient) were extremely affected due a large ulcerative lesion being on the face. The effect on quality of life was negligible in the majority of army patients as well (35.1% no effect, 31.9% small effect), with a few patients affected moderately and very largely (22.3 and 10.6%, respectively). The most affected domain in patients was symptoms and feeling 1.27 ± 1.400 (mean ± SD), and the least was the relationships domain 0.27 ± 0.625. CONCLUSION: CL does not seem to affect the quality of life in the majority of Sri Lankan patients when compared to CL in other parts of the world or other skin diseases.


Assuntos
Leishmaniose Cutânea/psicologia , Militares/psicologia , Qualidade de Vida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Leishmaniose Cutânea/complicações , Masculino , Pessoa de Meia-Idade , Estigma Social , Sri Lanka , Inquéritos e Questionários , Avaliação de Sintomas , Adulto Jovem
15.
Parasitology ; 145(4): 425-429, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29642962

RESUMO

Leishmania donovani, the most virulent species of Leishmania, is found in the South Asian region that harbours the majority of visceral leishmaniasis (VL) cases in the world. The traditionally accepted relationships between the causative species of Leishmania and the resultant disease phenotype have been challenged during recent years and have underscored the importance of revisiting the previously established taxonomy with revisions to its classification. The weak voice of the afflicted with decades of neglect by scientists and policy makers have led to the miserably inadequate and slow advancements in product development in the fields of diagnostics, chemotherapeutics and vector control that continue to hinder the effective management and control of this infection. Limitations notwithstanding, the regional drive for the elimination of VL initiated over a decade ago that focused on India, Nepal and Bangladesh, the three main afflicted countries in the Indian subcontinent is therefore, commendable, with the subsequent status reviews and restructuring of strategies possibly even more so. However, the renewed efforts would need to be combined with plans to combat new challenges in the South-Asian region that includes the emergence of atypical parasite variants, in order to realistically achieve the set goal of regional elimination of VL.


Assuntos
Erradicação de Doenças/métodos , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/prevenção & controle , Leishmaniose/prevenção & controle , Doenças Negligenciadas/epidemiologia , Psychodidae/parasitologia , Animais , Bangladesh/epidemiologia , Erradicação de Doenças/legislação & jurisprudência , Erradicação de Doenças/estatística & dados numéricos , Humanos , Índia/epidemiologia , Leishmania donovani/isolamento & purificação , Leishmaniose/epidemiologia , Leishmaniose/parasitologia , Leishmaniose/transmissão , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/transmissão , Doenças Negligenciadas/prevenção & controle , Nepal/epidemiologia
16.
Am J Trop Med Hyg ; 98(3): 759-762, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29345220

RESUMO

Cutaneous leishmaniasis (CL) is diagnosed mainly by light microscopy of smears made using lesion material. Histopathology is usually done in atypical presentations or when lesion smears are negative. Tissue impression smears (TIS) made from skin biopsy specimens were compared with histopathology for the diagnosis of CL. Out of the 111 patients included, 83 (74.8%) were positive by either methods. The TIS was positive in 70.3% whereas histopathology was positive in 56.8% of patients. Tissue impression smears can be used as a supplementary diagnostic test that gives sensitive and rapid results when tissue biopsies are used as the source of lesion material for diagnosis of CL.


Assuntos
Histocitoquímica/métodos , Leishmania donovani/ultraestrutura , Leishmaniose Cutânea/diagnóstico , Pele/patologia , Biópsia , Humanos , Leishmania donovani/patogenicidade , Leishmaniose Cutânea/parasitologia , Leishmaniose Cutânea/patologia , Microscopia , Pele/parasitologia , Sri Lanka
17.
BMC Infect Dis ; 17(1): 791, 2017 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-29273010

RESUMO

BACKGROUND: Leishmania donovani is the etiological agent of visceral leishmaniasis (VL) in the Indian subcontinent. However, it is also known to cause cutaneous leishmaniasis (CL) in Sri Lanka. Sri Lankan L. donovani differs from other L. donovani strains, both at the molecular and biochemical level. To investigate the different species or strain-specific differences of L. donovani in Sri Lanka we evaluated sequence variation of the kinetoplastid DNA (kDNA). METHODS: Parasites isolated from skin lesions of 34 CL patients and bone marrow aspirates from 4 VL patients were genotyped using the kDNA minicircle PCR analysis. A total of 301 minicircle sequences that included sequences from Sri Lanka, India, Nepal and six reference species of Leishmania were analyzed. RESULTS: Haplotype diversity of Sri Lankan isolates were high (H d = 0.757) with strong inter-geographical genetic differentiation (F ST > 0.25). In this study, L. donovani isolates clustered according to their geographic origin, while Sri Lankan isolates formed a separate cluster and were clearly distinct from other Leishmania species. Within the Sri Lankan group, there were three distinct sub-clusters formed, from CL patients who responded to standard antimony therapy, CL patients who responded poorly to antimony therapy and from VL patients. There was no specific clustering of sequences based on geographical origin within Sri Lanka. CONCLUSION: This study reveals high levels of haplotype diversity of L. donovani in Sri Lanka with a distinct genetic association with clinically relevant phenotypic characteristics. The use of genetic tools to identify clinically relevant features of Leishmania parasites has important therapeutic implications for leishmaniasis.


Assuntos
Variação Genética , Leishmania donovani/genética , Leishmaniose Cutânea/diagnóstico , Medula Óssea/parasitologia , Medula Óssea/patologia , Análise por Conglomerados , Estudos Transversais , DNA de Cinetoplasto/química , DNA de Cinetoplasto/genética , DNA de Cinetoplasto/metabolismo , Genótipo , Haplótipos , Humanos , Leishmania donovani/classificação , Leishmania donovani/isolamento & purificação , Leishmaniose Cutânea/epidemiologia , Leishmaniose Cutânea/parasitologia , Masculino , Filogenia , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Pele/parasitologia , Pele/patologia , Sri Lanka/epidemiologia
18.
Am J Trop Med Hyg ; 97(4): 1120-1126, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28820681

RESUMO

Leishmania donovani causes cutaneous leishmaniasis (CL) in Sri Lanka. Standard treatment is multiple, painful doses of intralesional sodium stibogluconate (IL-SSG). Treatment failures are increasingly reported, hence the need to investigate alternatives. Efficacy, safety, and cost-effectiveness of thermotherapy were assessed for the first time for L. donovani CL. A single blinded noninferiority randomized controlled trial was conducted on new laboratory-confirmed CL patients with single lesions (N = 213). Selected patients were randomly assigned to 1) test group (N = 98; single session of radiofrequency-induced heat therapy (RFHT) given at 50°C for 30 seconds) and 2) control group (N = 115; 1-3 mL IL-SSG given weekly, until cure/10 doses). Patients were followed-up fortnightly for 12 weeks to assess clinical cure. Cost of treatment was assessed using scenario building technique. Cure rates by 8, 10, and 12 weeks in RFHT group were 46.5%, 56.5%, and 65.9% as opposed to 28%, 40.8%, and 59.4% in IL-SSG group, with no major adverse events. Cure rate by RFHT was significantly higher at 8 weeks (P = 0.009, odds ratio [OR]: 2.236, confidence interval [CI]: 1.217-4.108) and 10 weeks (P = 0.035, OR: 1.881, CI: 1.044-3.388), but comparable thereafter. Cost of RFHT was 7 times less (USD = 1.54/patient) than IL-SSG (USD = 11.09/patient). A single application of RFHT is safe, cost-effective, and convenient, compared with multiple doses of IL-SSG in the treatment of L. donovani CL. Therefore, RFHT would be considered noninferior as per trial outcome when compared with standard IL-SSG therapy with multiple benefits for the patient and the national health care system.


Assuntos
Hipertermia Induzida , Leishmania donovani , Leishmaniose Cutânea/terapia , Leishmaniose Visceral/terapia , Adolescente , Adulto , Gluconato de Antimônio e Sódio/administração & dosagem , Gluconato de Antimônio e Sódio/uso terapêutico , Criança , Feminino , Humanos , Leishmaniose Cutânea/parasitologia , Leishmaniose Cutânea/patologia , Leishmaniose Visceral/parasitologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
BMC Infect Dis ; 17(1): 307, 2017 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-28438137

RESUMO

BACKGROUND: Following its recent certification as malaria-free, imported infections now pose the greatest threat for maintaining this status in Sri Lanka. Imported infections may also introduce species that are uncommon or not previously endemic to these areas. We highlight in this case report the increasing importance of less common malaria species such as Plasmodium ovale in elimination settings and discuss its relevance for the risk of malaria resurgence in the country. CASE PRESENTATION: A 41-year-old patient from southern Sri Lanka was diagnosed with malaria after 8 days of fever. Microscopy of blood smears revealed parasites morphologically similar to P. vivax and the rapid diagnostic test was indicative of non-P. falciparum malaria. He was treated with chloroquine over 3 days and primaquine for 14 days. He was negative for malaria at a one-year follow-up. Molecular testing performed subsequently confirmed that infection was caused by P. ovale curtisi. The patient gave a history of P. vivax malaria treated with chloroquine and primaquine. He also provided a history of travel to malaria endemic regions, including residing in Liberia from May 2012 to November 2013, throughout which he was on weekly malaria prophylaxis with mefloquine. He had also visited India on an eight-day Buddhist pilgrimage tour in September 2014 without malaria prophylaxis. CONCLUSIONS: It is crucial that every case of malaria is investigated thoroughly and necessary measures taken to prevent re-introduction of malaria. Accurate molecular diagnostic techniques need to be established in Sri Lanka for the screening and diagnosis of all species of human malaria infections, especially those that may occur with low parasitemia and are likely to be undetected using the standard techniques currently in use. In addition, ascertaining whether an infection occurred through local transmission or by importation is critical in the implementation of an effective plan of action in the country. This new era emphasizes the global nature of regional malaria elimination. Increasing global surveillance and tool development are necessary in order to "fingerprint" parasites and identify their origin.


Assuntos
Antimaláricos/uso terapêutico , Malária Vivax/parasitologia , Malária/diagnóstico , Plasmodium ovale/isolamento & purificação , Adulto , Cloroquina/uso terapêutico , Febre , Humanos , Libéria , Malária/tratamento farmacológico , Malária/epidemiologia , Malária/parasitologia , Malária Vivax/tratamento farmacológico , Masculino , Técnicas de Diagnóstico Molecular , Parasitemia , Plasmodium ovale/genética , Primaquina/uso terapêutico , Risco , Sri Lanka/epidemiologia , Viagem
20.
PLoS One ; 12(2): e0171208, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28152025

RESUMO

Glucose-6-Phosphate Dehydrogenase (G6PD) enzyme deficiency is known to offer protection against malaria and an increased selection of mutant genes in malaria endemic regions is expected. However, anti-malarial drugs such as primaquine can cause haemolytic anaemia in persons with G6PD deficiency. We studied the extent of G6PD deficiency in selected persons attending Teaching Hospitals of Anuradhapura and Kurunegala, two previously high malaria endemic districts in Sri Lanka. A total of 2059 filter-paper blood spots collected between November 2013 and June 2014 were analysed for phenotypic G6PD deficiency using the modified WST-8/1-methoxy PMS method. Each assay was conducted with a set of controls and the colour development assessed visually as well as with a microplate reader at OD450-630nm. Overall, 142/1018 (13.95%) and 83/1041 (7.97%) were G6PD deficient in Anuradhapura and Kurunegala districts respectively. The G6PD prevalence was significantly greater in Anuradhapura when compared to Kurunegala (P<0.0001). Surprisingly, females were equally affected as males in each district: 35/313 (11.18%) males and 107/705 (15.18%) females were affected in Anuradhapura (P = 0.089); 25/313 (7.99%) males and 58/728 (7.97%) females were affected in Kurunegala (P = 0.991). Prevalence was greater among females in Anuradhapura than in Kurunegala (P<0.05), while no such difference was observed between the males (P>0.05). Severe deficiency (<10% normal) was seen among 28/1018 (2.75%) in Anuradhapura (7 males; 21 females) and 17/1041 (1.63%) in Kurunegala (7 males; 10 females). Enzyme activity between 10-30% was observed among 114/1018 (11.20%; 28 males; 86 females) in Anuradhapura while it was 66/1041 (6.34%; 18 males; 48 females) in Kurunegala. Screening and educational programmes for G6PD deficiency are warranted in these high risk areas irrespective of gender for the prevention of disease states related to this condition.


Assuntos
Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Malária/epidemiologia , Adulto , Idoso , Anemia Hemolítica/induzido quimicamente , Anemia Hemolítica/etiologia , Antimaláricos/efeitos adversos , Estudos Transversais , Feminino , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Hospitais de Ensino/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores Sexuais , Sri Lanka/epidemiologia , Adulto Jovem
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