The Diagnostic Accuracy of Serologic and Molecular Methods for Detecting Visceral Leishmaniasis in HIV Infected Patients: Meta-Analysis

Human visceral leishmaniasis (VL), a potentially fatal disease, has emerged as an important opportunistic condition in HIV infected patients. In immunocompromised patients, serological investigation is considered not an accurate diagnostic method for VL diagnosis and molecular techniques seem especially promising. Demonstration of Leishmania parasites in bone marrow aspirate or in other biologic specimen, either by visualization or culture, remains the most reliable diagnostic technique in the setting of HIV co-infection. However, these tests are difficult to perform in rural areas and some of them are invasive and carry a risk of complication. This work is a systematic review to evaluate the accuracy of serologic and molecular tests for VL diagnosis in HIV-infected patients. Two reviewers searched the literature, evaluating quality of studies and comparing performance of diagnostic tests. Thirty three studies were included. Most studies were carried out in Europe. Serological tests varied in performance, but with overall limited sensitivity. Based on the evidence, serological tests should not be used to rule out a diagnosis of VL among HIV-patients, but a positive test at even low titers has diagnostic value when combined with the clinical case definition. Tests based on DNA detection are highly sensitive and may contribute to a diagnostic workup

Development and Validation of a PCR-ELISA for the Diagnosis of Symptomatic and Asymptomatic Infection by Leishmania (Leishmania) infantum

A kDNA PCR enzyme-linked immunosorbent assay (kDNA PCR-ELISA) for the diagnosis of human visceral leishmaniasis (HVL) was developed. The detection limit of the reaction, precision measurements, and cut-off of the kDNA PCR-ELISA were defined in a proof-of-concept phase. A reference strain of Leishmania (Leishmania) infantum and a bank of 14 peripheral blood samples from immunocompetent patients with VL were characterized using techniques considered gold standards, and 11 blood samples obtained from healthy individuals of an endemic area were also assessed. Phase II evaluation determined the performance of the assay in peripheral blood samples from 105 patients with VL (adults and children), 25 patients with Leishmania/HIV coinfection, 40 healthy individuals, and 33 asymptomatic individuals living in endemic areas. The kDNA PCR-ELISA exhibited satisfactory precision, with a detection limit of 0.07 fg of DNA from L. (L.) infantum and 1 parasite/mL blood. The overall sensitivity of the assay for all groups studied was 100% (95% confidence interval [CI]: 97.1–100%), and the specificity was 95% (95% CI: 83.5–98.6%). The kDNA PCR-ELISA was shown to be a useful tool for VL symptomatic and asymptomatic individuals diagnosis and its use in endemic countries may help monitor control interventions

Harmonized clinical trial methodologies for localized cutaneous leishmaniasis and potential for extensive network with capacities for clinical evaluation

International audienceINTRODUCTION: Progress with the treatment of cutaneous leishmaniasis (CL) has been hampered by inconsistent methodologies used to assess treatment effects. A sizable number of trials conducted over the years has generated only weak evidence backing current treatment recommendations, as shown by systematic reviews on old-world and new-world CL (OWCL and NWCL).MATERIALS AND METHODS: Using a previously published guidance paper on CL treatment trial methodology as the reference, consensus was sought on key parameters including core eligibility and outcome measures, among OWCL (7 countries, 10 trial sites) and NWCL (7 countries, 11 trial sites) during two separate meetings.RESULTS: Findings and level of consensus within and between OWCL and NWCL sites are presented and discussed. In addition, CL trial site characteristics and capacities are summarized.CONCLUSIONS: The consensus reached allows standardization of future clinical research across OWCL and NWCL sites. We encourage CL researchers to adopt and adapt as required the proposed parameters and outcomes in their future trials and provide feedback on their experience. The expertise afforded between the two sets of clinical sites provides the basis for a powerful consortium with potential for extensive, standardized assessment of interventions for CL and faster approval of candidate treatments

Efficacy of pentavalent antimoniate intralesional infiltration therapy for cutaneous leishmaniasis: A systematic review - Fig 3

<p>Initial response (A), initial cure (B) and definite cure (C) rates with Sb^v intralesional therapy in Old World leishmaniasis studies.</p

Efficacy of azole therapy for tegumentary leishmaniasis: A systematic review and meta-analysis

<div><p>Background</p><p>Several controlled and uncontrolled studies addressing azole antifungal drugs for cutaneous and mucosal leishmaniasis have been published with inconclusive results. We conducted a systematic literature review of studies evaluating the efficacy and toxicity associated with azole therapy for tegumentary leishmaniasis.</p><p>Methodology</p><p>PRISMA guidelines for systematic reviews and the Cochrane manual were followed, and the review methodology was registered (PROSPERO; CRD42016048668). Sources included the EMBASE, Web of Science, MEDLINE, LILACS, and IBECS databases along with a manual search of references from evaluated studies. Additional resources such as <i>Google Scholar</i> and clinicaltrials.gov were also searched. We included all studies reporting cure rate after cutaneous or mucosal leishmaniasis treatment with systemic azole drugs, regardless of their design. R software was used to estimate global rates of success and adverse events with each drug. The main outcome of interest was clinical cure, defined as complete re-epithelialization of all lesions.</p><p>Results</p><p>A total of 37 studies involving 1259 patients that reported outcomes after fluconazole (9), ketoconazole (14) and itraconazole (15) treatments were included. Only 14 (38%) were randomized controlled trials (RCT). The pooled azole final efficacy rate was 64% (CI95%: 57–70%) for all studies and 60% (CI95%: 50–70%) (p = 0.41) if only RCTs studies were considered. Twenty-four studies were conducted in the Old World and 13 studies in the Americas. The final efficacy rate according to New and Old World were 62% (CI95%: 43–77%) and 66% (CI95%: 58–73%), respectively. The final efficacy rate of azoles according to species were 89% (CI95%: 50–98%) for <i>L</i>. <i>mexicana</i>; 88% for <i>L</i>. <i>infantum</i> (CI95%: 27–99%); 80% for <i>L</i>. <i>donovani;</i> 53% (CI95%: 29–76%) for <i>L</i>. <i>major</i>; 49% for <i>L</i>. <i>braziliensis</i> (CI95%: 21–78%); and 15% (CI95%: 1–84%) for <i>L</i>. <i>tropica</i>. The cure rates were similar among the fluconazole, ketoconazole and itraconazole group arms (p = 0.89), specifically 61% (CI95%: 48–72%), 64% (CI95%: 44–80%) 65% (CI95%: 56–72%), respectively. Adverse events during fluconazole, itraconazole and ketoconazole therapy were reported in 7% (CI95%: 3–14%), 12% (CI95% 8–19%) and 13% (CI95%: 6–29%) of treated patients, respectively, without difference among them (p = 0.35). This systematic review included studies with small samples and both non-comparative and non-randomized studies and the main limitation was the low quality of the available studies.</p><p>Conclusions</p><p>Available evidence suggests that fluconazole, ketoconazole and itraconazole have similar and modest efficacy rates for tegumentary leishmaniasis treatment. There is insufficient evidence to support the exclusive use of azole therapy as a single agent for leishmaniasis treatment.</p></div

Characteristic of the population enrolled in azole arm in the Old World leishmaniasis studies.

<p>Characteristic of the population enrolled in azole arm in the Old World leishmaniasis studies.</p

Outcomes in Old World leishmaniasis studies.

<p>Outcomes in Old World leishmaniasis studies.</p

Outcome in Old World leishmaniasis studies.

<p>Outcome in Old World leishmaniasis studies.</p

Main methodological characteristics of the Old World leishmaniasis studies.

<p>Main methodological characteristics of the Old World leishmaniasis studies.</p