“…Five studies have a low risk of bias for domain flow and timing, with three having a high and one having an unclear risk of bias regarding this domain. Because there was no gold standard [ 45 ] or highly sensitive (100%) and specific test to correctly classify CL, all studies were judged unclear for the reference standard domain. Fig.…”
Background
Sensitive, robust, and fast point-of-care tests are needed for cutaneous leishmaniasis (CL) diagnosis. The recently developed CL Detect rapid test (InBios) for detecting Leishmania peroxidoxin antigen has been evaluated in several studies. However, diagnostic performances were controversial. Therefore, this systematic review and meta-analysis aimed to determine the pooled sensitivity and specificity of CL Detect for CL diagnosis.
Methods
PubMed, Scopus, EMBASE, ScienceDirect, and Google Scholar were sources of articles. We included studies reporting the diagnostic accuracy of CL Detect and CL-suspected patients in the English language. The methodological qualities of the included studies were appraised using the quality assessment of diagnostic accuracy studies-2 (QUADAS‐2). Meta-analysis was conducted using Stata 14.2 and R software.
Results
A total of 9 articles were included. The study sample size ranged from 11 to 274. The sensitivities of the individual studies ranged from 23 to 100%, and the specificities ranged from 78 to 100%. Pooled sensitivity and specificity were 68% (95% CI, 41–86%) and 94% (95% CI, 87–97%), respectively. AUC displayed 0.899. Pooled sensitivity was lower (47%, 95% CI, 34–61%) when PCR was used as a reference than microscopy (83%, 95% CI, 39–97%). Pooled sensitivity was lower (48%, 95% CI, 30–67%) for all lesion durations compared to ≤ 4 months (89%, 95% CI, 43–99%).
Conclusions
CL Detect has poor sensitivity and does not meet the minimal sensitivity of 95% of target product profiles designed for CL point-of-care tests. Currently, the CL Detect test looks unsuitable for CL diagnosis, despite its high specificity. Findings are limited by the low number of studies available. Further large-scale studies are recommended.
Systematic review registration
PROSPERO CRD42022323497.
“…Five studies have a low risk of bias for domain flow and timing, with three having a high and one having an unclear risk of bias regarding this domain. Because there was no gold standard [ 45 ] or highly sensitive (100%) and specific test to correctly classify CL, all studies were judged unclear for the reference standard domain. Fig.…”
Background
Sensitive, robust, and fast point-of-care tests are needed for cutaneous leishmaniasis (CL) diagnosis. The recently developed CL Detect rapid test (InBios) for detecting Leishmania peroxidoxin antigen has been evaluated in several studies. However, diagnostic performances were controversial. Therefore, this systematic review and meta-analysis aimed to determine the pooled sensitivity and specificity of CL Detect for CL diagnosis.
Methods
PubMed, Scopus, EMBASE, ScienceDirect, and Google Scholar were sources of articles. We included studies reporting the diagnostic accuracy of CL Detect and CL-suspected patients in the English language. The methodological qualities of the included studies were appraised using the quality assessment of diagnostic accuracy studies-2 (QUADAS‐2). Meta-analysis was conducted using Stata 14.2 and R software.
Results
A total of 9 articles were included. The study sample size ranged from 11 to 274. The sensitivities of the individual studies ranged from 23 to 100%, and the specificities ranged from 78 to 100%. Pooled sensitivity and specificity were 68% (95% CI, 41–86%) and 94% (95% CI, 87–97%), respectively. AUC displayed 0.899. Pooled sensitivity was lower (47%, 95% CI, 34–61%) when PCR was used as a reference than microscopy (83%, 95% CI, 39–97%). Pooled sensitivity was lower (48%, 95% CI, 30–67%) for all lesion durations compared to ≤ 4 months (89%, 95% CI, 43–99%).
Conclusions
CL Detect has poor sensitivity and does not meet the minimal sensitivity of 95% of target product profiles designed for CL point-of-care tests. Currently, the CL Detect test looks unsuitable for CL diagnosis, despite its high specificity. Findings are limited by the low number of studies available. Further large-scale studies are recommended.
Systematic review registration
PROSPERO CRD42022323497.
“…Additionally, the combination of epitopes derived from several distinct viral proteins with low reactivity among flaviviruses is clearly advantageous when compared to the use of full-length proteins. The successful use of multi-epitope chimeric proteins has been increasingly documented in the literature, and includes chimeric proteins for the diagnosis of Trypanosoma cruzi [ 47 ], Burkholderia pseudomallei [ 48 ], Human T-cell lymphotropic virus [ 49 , 50 ], Brucella [ 51 ], Leishmania braziliensis [ 52 ], among others. These publications also demonstrate the reliability and feasibility of a multi-epitope recombinant approach for diagnosis.…”
Zika virus (ZIKV), an arbovirus from the Flaviviridae family, is the causative agent of Zika fever, a mild and frequent oligosymptomatic disease in humans. Nonetheless, on rare occasions, ZIKV infection can be associated with Guillain-Barré Syndrome (GBS), and severe congenital complications, such as microcephaly. The oligosymptomatic disease, however, presents symptoms that are quite similar to those observed in infections caused by other frequent co-circulating arboviruses, including dengue virus (DENV). Moreover, the antigenic similarity between ZIKV and DENV, and even with other members of the Flaviviridae family, complicates serological testing due to the high cross-reactivity of antibodies. Here, we designed, produced in a prokaryotic expression system, and purified three multiepitope proteins (ZIKV-1, ZIKV-2, and ZIKV-3) for differential diagnosis of Zika. The proteins were evaluated as antigens in ELISA tests for the detection of anti-ZIKV IgG using ZIKV- and DENV-positive human sera. The recombinant proteins were able to bind and detect anti-ZIKV antibodies without cross-reactivity with DENV-positive sera and showed no reactivity with Chikungunya virus (CHIKV)- positive sera. ZIKV-1, ZIKV-2, and ZIKV-3 proteins presented 81.6%, 95%, and 66% sensitivity and 97%, 96%, and 84% specificity, respectively. Our results demonstrate the potential of the designed and expressed antigens in the development of specific diagnostic tests for the detection of IgG antibodies against ZIKV, especially in regions with the circulation of multiple arboviruses.
“…The plasmid p ET-28a( +)-MEP/TL was inserted into the electrocompetent Escherichia coli BL21 Arctic Express (DE3) cells (Agilent Technologies, USA), as previously described (Menezes-Souza et al 2015 ). Protein expression was induced by the addition of IPTG, and purification was performed using a chromatography column HisTrap HP affinity connected to an ÄKTAprime chromatography system (Cytiva, USA), as previously described (Garcia et al 2021 ). To remove endotoxin contamination, r MEP/TL was passed through a polymyxin-agarose column (Sigma-Aldrich, St. Louis, MO, USA) to remove any residual endotoxin content (< 10 ng of LPS per 1 mg of recombinant protein, measured by the quantitative Chromogenic Limulus Amebocyte Assay QCL-1000 (BioWhittaker, MD, USA) (Lage et al 2019 ; Ribeiro et al 2019 , 2020 ).…”
Tegumentary leishmaniasis (TL) is a disease of high severity and incidence in Brazil, and
Leishmania braziliensis
is its main etiological agent. The inefficiency of control measures, such as high toxicity and costs of current treatments and the lack of effective immunoprophylactic strategies, makes the development of vaccines indispensable and imminent. In this light, the present work developed a gene encoding multiple T-cell (CD4
+
/CD8
+
) epitope, derived from conserved proteins found in
Leishmania
species and associated with TL, to generate a chimeric protein (
r
MEP/TL) and compose a vaccine formulation. For this, six T-cell epitopes were selected by immunoinformatics approaches from proteins present in the amastigote stage and associated with host-parasite interactions. The following formulations were then tested in an
L. braziliensis
murine infection model:
r
MEP/TL in saline or associated with MPLA-PHAD
®
. Our data revealed that, after immunization (three doses; 14-day intervals) and subsequent challenging,
r
MEP/TL and
r
MEP/TL + MPLA-vaccinated mice showed an increased production of key immunological biomarkers of protection, such as IgG
2a
, IgG
2a
/IgG
1
, NO, CD4
+
, and CD8
+
T-cells with IFN-γ and TNF-α production, associated with a reduction in CD4
+
IL-10
+
and CD8
+
IL-10
+
T-cells. Vaccines also induced the development of central (CD44
high
CD62L
high
) and effector (CD44
high
CD62L
low
) memory of CD4
+
and CD8
+
T-cells. These findings, associated with the observation of lower rates of parasite burdens in the vaccinated groups, when compared to the control groups, suggest that immunization with
r
MEP/TL and, preferably, associated with an adjuvant, may be considered an effective tool to prevent TL.
Key points
•
Rational design approaches for vaccine development.
•
Central and effector memory of CD4+ and CD8+ T-cells.
•
Vaccine comprised of rMEP/TL plus MPLA as an effective tool to prevent TL.
Supplementary Information
The online version contains supplementary material available at 10.1007/s00253-022-12033-7.
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