Dataset Information

Systematic review on antigens for serodiagnosis of visceral leishmaniasis, with a focus on East Africa.

ABSTRACT:

Background

Accurate and accessible diagnosis is key for the control of visceral leishmaniasis (VL). Yet, current diagnostic tests for VL have severe limitations: they are invasive or not suitable as point of care (POC) test or their performance is suboptimal in East Africa. We analysed the antigens in the VL serodiagnostics development pipeline to identify shortcomings and to propose strategies in the development of an alternative POC test for VL in East Africa.

Objectives

The objective of this study was to identify and to analyse all antigens for VL serodiagnosis that have been published before 2018 in order to identify candidates and gaps in the pipeline for a new POC test in East Africa.

Methods

A systematic literature search was performed on PubMed for original research articles on Leishmania-specific antigens for antibody detection of VL in humans. From each article, the following information was extracted: the antigen name, test format and characteristics, its reported sensitivity and specificity and study cohort specifications.

Results

One hundred and seven articles containing information about 96 tests based on 89 different antigens were included in this study. Eighty six of these tests, comprising 80 antigens, were evaluated in phase I and II studies only. Only 20 antigens, all of which are native, contain a carbohydrate and/or lipid moiety. Twenty-four antigens, of which 7 are non-native, are composed of antigen mixtures. Nineteen tests, comprising 18 antigens, have been evaluated on East African specimens, of which only 2 (rK28 based immunochromatographic test and intact promastigote based indirect fluorescent antibody technique) consistently showed sensitivities above 94 and specificities above 97% in a phase III study and one in a phase II study (dot blot with SLA). Only rK28 is a non-native mixture of antigens which we consider suitable for further evaluation and implementation.

Conclusions

The development pipeline for an alternative serodiagnostic test for VL is almost empty. Most antigens are not sufficiently evaluated. Non-protein antigens and antigen mixtures are being neglected. We propose to expand the evaluation of existing antigen candidates and to investigate the diagnostic potential of defined non-native carbohydrate and lipid antigens for VL serodiagnosis in East Africa.

SUBMITTER: Kuhne V

PROVIDER: S-EPMC6711545 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Systematic review on antigens for serodiagnosis of visceral leishmaniasis, with a focus on East Africa.

Kühne Vera V Rezaei Zahra Z Pitzinger Paul P Büscher Philippe P

PLoS neglected tropical diseases 20190815 8

<h4>Background</h4>Accurate and accessible diagnosis is key for the control of visceral leishmaniasis (VL). Yet, current diagnostic tests for VL have severe limitations: they are invasive or not suitable as point of care (POC) test or their performance is suboptimal in East Africa. We analysed the antigens in the VL serodiagnostics development pipeline to identify shortcomings and to propose strategies in the development of an alternative POC test for VL in East Africa.<h4>Objectives</h4>The obj ...[more]

PMID: 31415564

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Project description:BACKGROUND:Visceral leishmaniasis (VL) is a vector-borne disease that is deadly if left untreated. Understanding which factors have prognostic value may help to focus clinical management and reduce case fatality. However, information about prognostic factors is scattered and conflicting. We conducted a systematic review and meta-analysis to identify prognostic factors for mortality among VL patients in East Africa. METHODOLOGY/PRINCIPAL FINDINGS:The review protocol was registered in PROSPERO (CRD42016043112). We included studies published in English after 1970 describing VL patients treated in East African health facilities. To be included, studies had to report on associations between clinical or laboratory factors and mortality during admission or during VL treatment, with a minimal study size of ten patients. Conference abstracts and evaluations of genetic or immunological prognostic factors were excluded. We searched for studies in MEDLINE and four other databases in December 2018. To assess the risk of bias in observational studies and clinical trials, we used the Quality in Prognostic Studies (QUIPS) tool. We included 48 studies in the systematic review, describing 150,072 VL patients of whom 7,847 (5.2%) died. Twelve prognostic factors were evaluated in five or more studies and these results were submitted to meta-analysis producing one pooled crude odds ratio (OR) per prognostic factor. The following factors were strongly (OR>3) and significantly (P-value<0.05) associated with mortality: jaundice (OR = 8.27), HIV (OR = 4.60), tuberculosis (OR = 4.06), age >45 years (OR = 3.69), oedema (OR = 3.52), bleeding (OR = 3.37), and haemoglobin ?6.5 g/dl (OR = 3.26). Factors significantly and moderately (OR between one and three) associated with death were severe malnutrition, long duration of illness, young age (<5 years), and large spleen size. CONCLUSIONS/SIGNIFICANCE:These prognostic factors can be identified by health professionals in resource-constrained settings. They should be considered as "core" prognostic factors in future studies that aim at improving the prognosis of VL patients.

Project description:ObjectiveThe main objective of this study was to identify, describe, classify and analyze the scientific health economic evidence of VL-related technologies.MethodsA web search of combinations of free text and Mesh terms related to the economic evaluation of visceral leishmaniasis was conducted on scientific publication databases (Web of Science, Scopus, Medline via the Pubmed and Lilacs). A manual search of references lists of articles previously identified by the authors was also included. Articles written in English, Portuguese, Spanish or French were considered suitable for inclusion. Articles that matched the inclusion criteria were screened by at least two researchers, who extracted information regarding the epidemiologic scenario and methodological issues on a standardized form.ResultsThe initial search retrieved 107 articles, whose abstracts were inspected according to the inclusion criteria leading to a first selection of 49 (46%) articles. After the elimination of duplicates, the list was reduced to 21 (20%) articles. After careful reading and application of exclusion criteria, 14 papers were eligible according to the description, classification and analysis process proposed by the study. When classified by type of economic evaluation, articles were 7 (50%) cost-effectiveness, 5 (36%) cost-minimization, 1(7%) cost-benefit, and 1(7%) budget impact. When classified by methodology, studies were mainly nested to clinical-trials ("piggy back") 8(57%). Discount rates for outcomes and costs were present in 3 (43%) of the cost-effectiveness studies, and according to WHO's recommendations, the discount rate of 3% was used in all studies.ConclusionsThis article showed that health economic evaluations on visceral leishmaniasis used a wide range of technologies and methods. Nevertheless it is important to point out the geographic concentration of studies, which makes their transferability uncertain to different epidemiological scenarios, especially those concerning visceral leishmaniasis caused by Leishmania infantum.

Project description:BackgroundAntimicrobial resistance is currently a recognized global health problem stemming from poor antibiotic stewardship by health workers and inappropriate antimicrobial use by patients. Data showing the extent of poor antimicrobial stewardship in low- and middle-income countries are scanty though high incidences of antimicrobial resistance are increasingly reported in many settings across the globe. The objective of the present study was, therefore, to evaluate prescriptions for antimicrobials in East Africa.MethodsA comprehensive literature search strategy that includes text words and medical subject headings was developed and applied to predefined electronic databases. Two authors independently screened the titles and abstracts of the outputs of the literature search. Full texts were then independently reviewed by the first and the second authors. Eligible studies were formally assessed for quality and risk of bias using a scoring tool. Extracted data from included studies were combined in a meta-analysis where appropriate and presented using forest plots and tables or in a narrative text. Where data were available, subgroup analyses were performed.ResultsA total of 4284 articles were retrieved, but only 26 articles were included in the review. The majority of the included studies (30.8%) were retrieved from Ethiopia, followed by Sudan, Kenya, and Tanzania each contributing 19.2% of the included studies. The overall proportion of encounters with antimicrobials reported by the included studies was 57% CI [42-73%]. Ethiopia had an overall patient encounter with antimicrobials of 63% [50-76%] followed by Sudan with an overall encounter with antimicrobials of 62% CI [34-85%]. Included studies from Kenya reported an overall encounter with antimicrobials of 54% CI [15-90%], whereas included studies from Tanzania reported an overall patient encounter with antimicrobials of 40% CI [21-60%].ConclusionPrescription patterns demonstrated in this review significantly deviate from WHO recommendations suggesting inappropriate antimicrobial use in the East African countries. Further studies have to be pursued to generate more information on antimicrobial use in this region.

Dataset Information

Systematic review on antigens for serodiagnosis of visceral leishmaniasis, with a focus on East Africa.

Background

Objectives

Methods

Results

Conclusions

Publications

Systematic review on antigens for serodiagnosis of visceral leishmaniasis, with a focus on East Africa.

Similar Datasets

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