Krolewiecki AJ

Date: 
05/10/2017
Investigation Line: 

Abstract

Leishmania (Viannia) braziliensis is the species most frequently implicated with cutaneous and mucosal leishmaniasis in the Americas; its diagnosis is based on the identification of amastigotes in lesions, which is limited by low parasite burden. Leishmanin Skin Test (LST) is a support tool for diagnosis, based on delayed type hypersensitivity responses to Leishmania antigens injected intradermally, used in endemic areas as a complement to diagnosis. A retrospective analysis of individuals evaluated for their first episode of tegumentary leishmaniasis at a reference center in Argentina during the period 2006–2015 was performed, with the goal of assessing its usefulness as a support tool in the diagnosis of leishmaniasis. Demographic, clinical and diagnostic work-up were analyzed in individuals with clinically compatible lesions, lesion`s smear and LST. A total of 733 cases that met the case definition were included in the analysis; 678 (93%) localized cutaneous cases, 50 (7%) with mucosal involvement and 5 (<1%) disseminated. Diagnostic confirmation was reached in 474 (65%) cases through positive smears from skin or mucosal lesions, with only 6 cases among this group having negative LST. Among smear negative cases, 190 were negative also by LST, but in 69 instances LST was positive. Across age groups, similar ratios of sensitivity between smear and LST were calculated. Lesions older than 21 days-old were found to correlate with positive results both for smear and LST significantly more than younger lesions. These findings support the clinical use of LST as a diagnostic complement for American Cutaneous Leishmaniasis across all age groups even in endemic areas. In this analysis, the correlation with smear was high. Standardization of this technique and further research into its most adequate preparation and utilization protocols across different sites will help in the management of suspicious clinical cases.

Date: 
10/02/2015
Investigation Line: 

Abstract

BACKGROUND:

Traditional faecal-based methods have poor sensitivity for the detection of S. stercoralis, therefore are inadequate for post-treatment evaluation of infected patients who should be carefully monitored to exclude the persistence of the infection. In a previous study, we demonstrated high accuracy of five serology tests for the screening and diagnosis of strongyloidiasis. Aim of this study is to evaluate the performance of the same five tests for the follow up of patients infected with S. stercoralis.

METHODS:

Retrospective study on anonymized, cryo-preserved samples available at the Centre for Tropical Diseases (Negrar, Verona, Italy). Samples were collected before and from 3 to 12 months after treatment. The samples were tested with two commercially-available ELISA tests (IVD, Bordier), two techniques based on a recombinant antigen (NIE-ELISA and NIE-LIPS) and one in-house IFAT. The results of each test were evaluated both in relation to the results of fecal examination and to those of a composite reference standard (classifying as positive a sample with positive stools and/or at least three positive serology tests). The associations between the independent variables age and time and the dependent variable value of serological test (for all five tests), were analyzed by linear mixed-effects regression model.

RESULTS:

A high proportion of samples demonstrated for each test a seroreversion or a relevant decline (optical density/relative light units halved or decrease of at least two titers for IFAT) at follow up, results confirmed by the linear mixed effects model that showed a trend to seroreversion over time for all tests. In particular, IVD-ELISA (almost 90% samples demonstrated relevant decline) and IFAT (almost 87%) had the best performance. Considering only samples with a complete negativization, NIE-ELISA showed the best performance (72.5% seroreversion).

CONCLUSIONS:

Serology is useful for the follow up of patients infected with S. stercoralis and determining test of cure.

Date: 
09/08/2014
Investigation Line: 

Abstract

BACKGROUND:

Robust reference values for fecal egg count reduction (FECR) rates of the most widely used anthelmintic drugs in preventive chemotherapy (PC) programs for controlling soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, and hookworm) are still lacking. However, they are urgently needed to ensure detection of reduced efficacies that are predicted to occur due to growing drug pressure. Here, using a standardized methodology, we assessed the FECR rate of a single oral dose of mebendazole (MEB; 500 mg) against STHs in six trials in school children in different locations around the world. Our results are compared with those previously obtained for similarly conducted trials of a single oral dose of albendazole (ALB; 400 mg).

METHODOLOGY:

The efficacy of MEB, as assessed by FECR, was determined in six trials involving 5,830 school children in Brazil, Cambodia, Cameroon, Ethiopia, United Republic of Tanzania, and Vietnam. The efficacy of MEB was compared to that of ALB as previously assessed in 8,841 school children in India and all the above-mentioned study sites, using identical methodologies.

PRINCIPAL FINDINGS:

The estimated FECR rate [95% confidence interval] of MEB was highest for A. lumbricoides (97.6% [95.8; 99.5]), followed by hookworm (79.6% [71.0; 88.3]). For T. trichiura, the estimated FECR rate was 63.1% [51.6; 74.6]. Compared to MEB, ALB was significantly more efficacious against hookworm (96.2% [91.1; 100], p<0.001) and only marginally, although significantly, better against A. lumbricoides infections (99.9% [99.0; 100], p = 0.012), but equally efficacious for T. trichiura infections (64.5% [44.4; 84.7], p = 0.906).

CONCLUSIONS/SIGNIFICANCE:

A minimum FECR rate of 95% for A. lumbricoides, 70% for hookworm, and 50% for T. trichiura is expected in MEB-dependent PC programs. Lower FECR results may indicate the development of potential drug resistance.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01087099 NCT01379326.

Date: 
01/01/2014
Investigation Line: 

Abstract

A systematic review of surveys performed between 1980 and 2011 (published in MEDLINE/Pubmed and/or LILACS indexed journals, available in the baseline data from a Mass Deworming National Program (MDNP, 2005) was used to identify the prevalence, distribution and detection of risk areas for soil transmitted helminth infections (STH) in Argentina. We found 310 publications in the database using the pre-defined key-words (medical subject headings) for research purposes. Only 24 articles with 26 surveillance sites in 8 provinces and a total of 5495 surveyed individuals fulfilled the inclusion criteria. Frequency rates for STH had a wide range: Ascaris lumbricoides: 0-67%, hookworms: 0-90%, Trichuris trichiura: 0-24.6 and Strongyloides stercoralis: 0-83%. The estimated combined incidence varied from 0.8% to 88.6%. Baseline surveys from the MDNP reporting on 1943 children from 12 provinces confirmed the heterogeneity, with combined STH frequency rates ranging from 0 to 42.7%. Surveys included in this review showed that the distribution of STH in Argentina is not homogeneous, with areas of high incidence (> 20%) in the northeastern and northwestern provinces where mass deworming activities would be highly beneficial. In several surveys, the high overall incidence was mostly due to hookworms and S. stercoralis, a situation to be considered when selecting diagnostic and therapeutic control strategies. The scarcity or absence of data from various provinces and the availability of less than 8000 surveyed individuals should be considered.

Date: 
09/01/2014
Investigation Line: 

Abstract

BACKGROUND:

The diagnosis of Strongyloides stercoralis (S. stercoralis) infection is hampered by the suboptimal sensitivity of fecal-based tests. Serological methods are believed to be more sensitive, although assessing their accuracy is difficult because of the lack of sensitivity of a fecal-based reference ("gold") standard.

METHODS:

The sensitivity and specificity of 5 serologic tests for S. stercoralis (in-house IFAT, NIE-ELISA and NIE-LIPS and the commercially available Bordier-ELISA and IVD-ELISA) were assessed on 399 cryopreserved serum samples. Accuracy was measured using fecal results as the primary reference standard, but also using a composite reference standard (based on a combination of tests).

RESULTS:

According to the latter standard, the most sensitive test was IFAT, with 94.6% sensitivity (91.2-96.9), followed by IVD-ELISA (92.3%, 87.7-96.9). The most specific test was NIE-LIPS, with specificity 99.6% (98.9-100), followed by IVD-ELISA (97.4%, 95.5-99.3). NIE-LIPS did not cross-react with any of the specimens from subjects with other parasitic infections. NIE-LIPS and the two commercial ELISAs approach 100% specificity at a cut off level that maintains ≥70% sensitivity.

CONCLUSIONS:

NIE-LIPS is the most accurate serologic test for the diagnosis of S. stercoralis infection. IFAT and each of the ELISA tests are sufficiently accurate, above a given cut off, for diagnosis, prevalence studies and inclusion in clinical trials.

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