Dataset Information

Antigen Detection in Urine for Noninvasive Diagnosis and Treatment Monitoring of Visceral Leishmaniasis in Human Immunodeficiency Virus Coinfected Patients: An Exploratory Analysis from Ethiopia.

ABSTRACT: Diagnosis of visceral leishmaniasis (VL) and assessment of treatment response in human immunodeficiency virus (HIV)-coinfected patients still relies on invasive tissue aspiration. This hampers scale-up and decentralization of care in resource-limited settings. Noninvasive diagnostics are urgently needed. KATEX is a frequently used latex agglutination test for Leishmania antigen in urine that has never been evaluated in HIV-coinfected individuals from Leishmania donovani-endemic areas. This was an exploratory sub-study embedded within the screening phase of a trial in highly endemic northwestern Ethiopia. All patients were HIV-positive and aspirate-confirmed VL cases. We assessed diagnostic accuracy of KATEX for VL diagnosis and as test of cure at end of treatment, using tissue aspirate parasite load as reference methods. We also described the evolution of weekly antigen levels during treatment. Most of the 87 included patients were male (84, 97%), young (median age 31 years), and had poor immune status (median cluster of differentiation type 4 count 56 cells/?L). KATEX had moderate sensitivity (84%) for VL diagnosis. KATEX had moderate sensitivity (82%) and a moderate negative predictive value (87%) but only low specificity (49%) and a low positive predictive value (40%) for the assessment of treatment outcomes. Weekly antigen levels showed characteristic patterns during treatment of patients with different initial parasite loads and treatment outcomes. Antigen detection in urine using KATEX can contribute to improved VL diagnosis in HIV-coinfected patients but has limited use for monitoring of treatment response. Better noninvasive diagnostics are needed to reduce reliance on invasive methods and thus to expand and improve clinical care for VL in resource-limited settings.

SUBMITTER: Vogt F

PROVIDER: S-EPMC6159592 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Antigen Detection in Urine for Noninvasive Diagnosis and Treatment Monitoring of Visceral Leishmaniasis in Human Immunodeficiency Virus Coinfected Patients: An Exploratory Analysis from Ethiopia.

Vogt Florian F Mengesha Bewketu B Asmamaw Helen H Mekonnen Tigist T Fikre Helina H Takele Yegnasew Y Adem Emebet E Mohammed Rezika R Ritmeijer Koert K Adriaensen Wim W Melsew Yayehirad Y van Griensven Johan J Diro Ermias E

The American journal of tropical medicine and hygiene 20181001 4

Diagnosis of visceral leishmaniasis (VL) and assessment of treatment response in human immunodeficiency virus (HIV)-coinfected patients still relies on invasive tissue aspiration. This hampers scale-up and decentralization of care in resource-limited settings. Noninvasive diagnostics are urgently needed. KATEX is a frequently used latex agglutination test for <i>Leishmania</i> antigen in urine that has never been evaluated in HIV-coinfected individuals from <i>Leishmania donovani</i>-endemic are ...[more]

PMID: 30084342

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Project description:Background: Biomarkers predicting the risk of VL treatment failure and relapse in VL/HIV coinfected patients are needed. Nested within a two-site clinical trial in Ethiopia (2011-2015), we conducted an exploratory study to assess whether (1) levels of Leishmania antigenuria measured at VL diagnosis were associated with initial treatment failure and (2) levels of Leishmania antigenuria at the end of treatment (parasitologically-confirmed cure) were associated with subsequent relapse. Methods:Leishmania antigenuria at VL diagnosis and cure was determined using KAtex urine antigen test and graded as negative (0), weak/moderate (grade 1+/2+) or strongly-positive (3+). Logistic regression and Kaplan-Meier methods were used to assess the association between antigenuria and (1) initial treatment failure, and (2) relapse over the 12 months after cure, respectively. Results: The analysis to predict initial treatment failure included sixty-three coinfected adults [median age: 30 years interquartile range (IQR) 27-35], median CD4 count: 56 cells/?L (IQR 38-113). KAtex results at VL diagnosis were negative in 11 (17%), weak/moderate in 17 (27%) and strongly-positive in 35 (36%). Twenty (32%) patients had parasitologically-confirmed treatment failure, with a risk of failure of 9% (1/11) with KAtex-negative results, 0% (0/17) for KAtex 1+/2+ and 54% (19/35) for KAtex 3+ results. Compared to KAtex-negative patients, KAtex 3+ patients were at increased risk of treatment failure [odds ratio 11.9 (95% CI 1.4-103.0); P: 0.025]. Forty-four patients were included in the analysis to predict relapse [median age: 31 years (IQR 28-35), median CD4 count: 116 cells/?L (IQR 95-181)]. When achieving VL cure, KAtex results were negative in 19 (43%), weak/moderate (1+/2+) in 10 (23%), and strongly positive (3+) in 15 patients (34%). Over the subsequent 12 months, eight out of 44 patients (18%) relapsed. The predicted 1-year relapse risk was 6% for KAtex-negative results, 14% for KAtex 1+/2+ and 42% for KAtex 3+ results [hazard ratio of 2.2 (95% CI 0.1-34.9) for KAtex 1+/2+ and 9.8 (95% CI 1.8-82.1) for KAtex 3+, compared to KAtex negative patients; P: 0.03]. Conclusion: A simple field-deployable Leishmania urine antigen test can be used for risk stratification of initial treatment failure and VL relapse in HIV-patients. A dipstick-format would facilitate field implementation.

Project description:BackgroundVisceral Leishmaniasis (VL), a severe parasitic disease, could be fatal if diagnosis and treatment is delayed. Post kala-azar dermal leishmaniasis (PKDL), a skin related outcome, is a potential reservoir for the spread of VL. Diagnostic tests available for VL such as tissue aspiration are invasive and painful although they are capable of evaluating the treatment response. Serological tests although less invasive than tissue aspiration are incompetent to assess cure. Parasitological examination of slit-skin smear along with the clinical symptoms is routinely used for diagnosis of PKDL. Therefore, a noninvasive test with acceptable sensitivity and competency, additionally, to decide cure would be an asset in disease management and control.Methodology/principal findingsWe describe here, the development of antibody-capture ELISA and field adaptable dipstick test as noninvasive diagnostic tools for VL and PKDL and as a test of cure in VL treatment. Sensitivity and specificity of urine-ELISA were 97.94% (95/97) and 100% (75/75) respectively, for VL. Importantly, dipstick test demonstrated 100% sensitivity (97/97) and specificity (75/75) in VL diagnosis. Degree of agreement of the two methods with tissue aspiration was 98.83% (κ = 0.97) and 100% (κ = 1), for ELISA and dipstick test, respectively. Both the tests had 100% positivity for PKDL (14/14) cases. ELISA and dipstick test illustrated treatment efficacy in about 90% (16/18) VL cases when eventually turned negative after six months of treatment.Conclusions/significanceELISA and dipstick test found immensely effective for diagnosis of VL and PKDL through urine samples thus, may substitute the existing invasive diagnostics. Utility of these tests as indirect methods of monitoring parasite clearance can define infected versus cured. Urine-based dipstick test is simple, sensitive and above all noninvasive method that may help not only in active VL case detection but also to ascertain treatment response. It can therefore, be deployed widely for interventions in disease management of VL particularly in poor resource outskirts.

Dataset Information

Antigen Detection in Urine for Noninvasive Diagnosis and Treatment Monitoring of Visceral Leishmaniasis in Human Immunodeficiency Virus Coinfected Patients: An Exploratory Analysis from Ethiopia.

Publications

Antigen Detection in Urine for Noninvasive Diagnosis and Treatment Monitoring of Visceral Leishmaniasis in Human Immunodeficiency Virus Coinfected Patients: An Exploratory Analysis from Ethiopia.

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