This review is an update of an earlier narrative review published in 2015 on developments in the clinical management of cutaneous leishmaniasis (CL) including diagnosis, treatment, prevention and control measurements. CL is a vector-borne infection caused by the protozoan parasite Leishmania . The vector is the female sandfly. Globally, CL affects 12 million cases and annually 2 million new cases occur. CL is endemic in almost 100 countries and the total risk population is approximately 350 million people. WHO lists CL an emerging and uncontrolled disease and a neglected tropical disease. Local experience-based evidence remains the mainstay for the management of CL. Whereas intralesional therapeutic options are the first treatment option for most CL patients, those with mucocutaneous and disseminated involvement require a systemic therapeutic approach. Moreover, different Leishmania species can vary in their treatment outcomes. Therefore, species determination is critical for optimal CL clinical management. New DNA techniques allow for relatively easy Leishmania species determination, yet they are not easily implemented in resource-limited settings. There is a desperate need for novel, less toxic, and less painful treatment options, especially for children with CL. Yet, the large and well conducted studies required to provide the necessary evidence are lacking. To further control and potentially eliminate CL, we urgently need to improve vector control, and diagnostics, and we require efficient and safe vaccines. Alas, since CL primarily affects poor people, biotechnical companies dedicate little investment into the research programs that could lead to diagnostic, pharmaceutical, and vaccine innovations.
Background In order to expedite the development of new oral treatment regimens for visceral leishmaniasis (VL), there is a need for early markers to evaluate treatment response and predict long-term outcomes. Methods Data from three clinical trials were combined in this study, where Eastern African VL patients received various antileishmanial therapies. Leishmania kinetoplast DNA was quantified in whole blood with real-time quantitative PCR (qPCR) before, during and up to six months after treatment. The predictive performance of pharmacodynamic parameters for clinical relapse was evaluated using receiver-operating characteristic curves. Clinical trial simulations were performed to determine the power associated with the use of blood parasite load as a surrogate endpoint to predict clinical outcome at six months. Results The absolute parasite density on day 56 after start of treatment was found to be a highly sensitive predictor of relapse within six months of follow-up at a cut-off of 20 parasites/mL (AUC 0.92, specificity 0.91, sensitivity 0.89). Blood parasite loads correlated well with tissue parasite loads (ρ= 0.80) and with microscopy gradings of bone marrow and spleen aspirate smears. Clinical trial simulations indicated a >80% power to detect a difference in cure rate between treatment regimens if this difference was high (>50%) and when minimally 30 patients were included per regimen. Conclusion Blood Leishmania parasite load determined by qPCR is a promising early biomarker to predict relapse in VL patients. Once optimized, it might be useful in dose finding studies of new chemical entities.
Background Visceral Leishmaniasis (VL) is a severely neglected disease affecting millions of people with high mortality if left untreated. In Ethiopia, the primary laboratory diagnosis of VL is by using an antigen from a 39-amino acid sequence repeat of a kinesin-related (rK39) of leishmania donovani complex (L. donovani), rapid diagnostic tests (RDT). Different rk39 RDT brands are available with very variable performance and studies from Ethiopia showed a very wide range of sensitivity and specificity. Therefore, a systematic review and meta-analysis were conducted to determine the pooled sensitivity and specificity of rk39 RDT in Ethiopia. Method PUBMED, EMBASE, and other sources were searched using predefined search terms to retrieve all relevant articles from 2007 to 2020. Heterogeneity was assessed by visually inspecting summary receiver operating curves (SROC), Spearman correlation coefficient (rs), Cochran Q test statistics, inconsistency square (I2) and subgroup analysis. The presence and statistical significance of publication bias were assessed by Egger's test at p < 0.05, and all the measurements showed the presence of considerable heterogeneity. Quality assessment of diagnostic accuracy studies (QUADAS-2) checklists was used to check the qualities of the study. Results A total of 664 articles were retrieved, and of this 12 articles were included in the meta-analysis. Overall pooled sensitivity and specificity of the rk39 RDT to diagnose VL in Ethiopia were 88.0% (95% CI 86.0% to 89.0%) and 84.0% (95% CI 82.0% to 86.0%), respectively. The sensitivity and specificity of the rk39 RDT commercial test kits were DiaMed: 86.9% (95% CI 84.3% to 89.1%) and 82.2% (95% CI 79.3% to 85.0%), and InBios: 80.0% (95% CI 77.0% to 82.8%) and 97.4% (95% CI 95.0% to 98.8%), respectively. Conclusion Referring to our result, rk39 RDT considered an essential rapid diagnostic test for VL diagnosis. Besides to the diagnostic accuracy, the features such as easy to perform, quick (10–20 min), cheap, equipment-free, electric and cold chain free, and result reproducibility, rk39 RDT is advisable to remains in practice as a diagnostic test at least in the remote VL endemic localities till a better test will come.
The parasitic disease leishmaniasis is caused by protozoa of the genus Leishmania which are transmitted by sand fly vectors of the genus Phlebotomus in the Old World and Lutzomyia in the New World. Transmission can either be anthroponotic (human to human) or zoonotic through mammalian reservoirs such as dogs and rodents. Leishmaniasis has three principal clinical manifestations, namely cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), and visceral leishmaniasis (VL). The cutaneous form characteristically causes skin ulcers, the mucocutaneous form manifests as lesions of skin, mouth, and nose, and the (potentially lethal) visceral form affects the internal organs such as spleen and liver and also invades the bone marrow. Leishmaniasis is endemic in about ninety-eight countries and the diverse types of the disease occur in different regions of the world. CL is most common in Afghanistan, Algeria, Pakistan, Iran, Brazil, and Colombia; MCL is mainly restricted to countries of the Amazon Basin; and VL is most frequently seen in the Indian sub-continent, the Horn of Africa (Sudan and Ethiopia), and Brazil. The current global prevalence is estimated at about 12 million, and each year, the disease in one of its forms makes about 2 million new victims and claims up to 50,000 fatalities. This paper presents epidemiological, biological, and clinical aspects of leishmaniasis throughout the world; then focuses on the disease in the Republic of Suriname (South America); addresses in more detail the species of Leishmania parasites in that country; and concludes with potential future directions to improve our understanding of leishmaniasis in Suriname.
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