La leishmaniasis es una parasitosis producida por diferentes especies de protozoos del género Leishmania. Se la considera endémica en varios países del. Leishmaniasis is a disease caused by parasites of the Leishmania type. It is spread by the bite of certain types of sandflies. The disease can present in three. Study of cutaneous leishmaniasis in the State of Campeche (Yucatan Peninsula), Mexico, over a period of two years. Estudio de la leishmaniasis cutánea en el.
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This review focuses on recent developments in the diagnosis, treatment, management, and strategies cytanea the prevention and control of cutaneous leishmaniasis CL caused by both Old and New World Leishmania species.
CL is caused by the vector-borne protozoan parasite Leishmania and is transmitted via infected female sandflies. The disease is endemic in more than 98 countries and an estimated million people are at risk.
Cutaneous Leishmaniasis: Recent Developments in Diagnosis and Management
The overall prevalence is 12 million cases and the annual incidence is 2—2. The World Health Organization considers CL a severely neglected disease and a category 1 emerging and uncontrolled disease. The management of CL differs from region to region and is primarily based on local experience-based evidence.
Most CL patients can be treated with topical treatments, but some Leishmania species can cause mucocutaneous involvement requiring a systemic therapeutic approach. Moreover, Leishmania species can vary in their sensitivity to available therapeutic options. This makes species determination critical for the choice of treatment and the clinical outcome of CL.
Identification of the infecting parasite used to be laborious, but now the Leishmania species can be identified relatively easy with new Cutamea techniques that enable a more rational therapy choice. Current treatment guidelines for CL are based on poorly designed and reported trials. There is a lack of evidence for potentially beneficial treatments, a desperate need for large keishmaniasis studies, and standardization of future trials. Moreover, intensified research programs to improve vector control, diagnostics, and the therapeutic arsenal to contain further incidence and morbidity are needed.
Leishmaniasis is caused by vector-borne protozoan parasites of the genus Leishmania and transmitted via infected female sandflies Phlebotomus and Lutzomyia. In most countries, the incidence numbers are probably underestimated because cases are not recognized and reporting is not mandatory [ 1 ].
Depending on the infecting species, an infection with Leishmania parasites can give rise to three clinical manifestations. The first is leishmanjasis cutaneous leishmaniasis CL with single to multiple skin ulcers, satellite lesions, or nodular lymphangitis. The second is CL with mucosal involvement MCL and the third is systemic visceral leishmaniasis VL with involvement of internal organs, such as the liver, spleen, and bone marrow, which is lethal if not appropriately treated [ 2 ].
According to the Eurocentric world view, Leishmania parasites are divided into Old World species: Whereas most Old World species cause self-limiting ulcers in most cases, New World species cause a syndrome called American tegumentary leishmaniasis comprising CL plus a variety of other manifestations, such as MCL and the much rarer diffuse and disseminated cutaneous leishmaniasis DCL [ 4 ].
Apart from the variety of species-driven clinical manifestations, Leishmania species vary in sensitivity to available therapies [ 5 ]. This makes species determination critical for the clinical outcome of leishmaniasis.
Leishmaniasis cutánea | Actas Dermo-Sifiliográficas (English Edition)
In contrast to many other infectious diseases, identification of the infecting Leishmania parasite used to be laborious. Leishmania parasites can now be identified relatively easy with new DNA techniques. Two recent Cochrane reviews on the current treatment for Old and New World Leishmaniasus conclude that most clinical treatment trials have been designed and reported poorly, resulting in a lack of evidence for potentially beneficial treatments [ elishmaniasis7 ].
This can in part be attributed to the lack of financial incentive for pharmaceutical companies to invest in the development of drugs for a disease that is believed to primarily affect people that lack financial resources. Moreover, drug trials for CL are challenging because the disease mainly occurs in remote areas; as a result, proper follow-up is problematic and many studies have been affected by a considerable number of loss to follow-up events. There is a desperate need for large well-conducted studies that evaluate long-term effects leishmanjasis current therapies, and it is suggested that an international platform should be created to improve the quality and standardization of future trials to inform clinical practice.
As a category 1 emerging and uncontrolled disease, leishmaniasis is considered a severely neglected disease and intensified research programs to improve vector cutanew, diagnostics, and the therapeutic arsenal to contain further incidence and morbidity are oeishmaniasis. In this review, we focus on recent developments in the diagnosis, treatment, prevention, and strategies for the management ldishmaniasis control of CL caused by both Old and New World species.
The following publication languages were included: English, French, Spanish, and Portuguese. The search was narrowed down by using the following items: The diagnosis of CL is based on clinical features supported by epidemiologic data and laboratory testing. The selection of the diagnostic test employed often depends on the available infrastructure and resources of the diagnostic facility and not on diagnostic accuracy.
Here, we selected only general employed diagnostic methodologies leishamniasis discussion. Parasitologic diagnosis is still considered the gold standard in leishmaniasis diagnosis because of its high specificity. This is typically undertaken by histopathologic examination of fixed tissue or parasite in vitro culture from material from suspected lesions.
Microscopical diagnosis of CL is performed by the direct identification of amastigotes in Giemsa-stained lesion smears of biopsies, scrapings, or impression smears. The material from the ulcer margin usually has the highest yield. A comparative study between widely used scraping smears and fine needle aspiration cytology found a leishhmaniasis difference between the two methods in favor of fine leishmajiasis aspiration in the detection of amastigotes and microgranuloma, slide background, and patient comfort [ 10 ].
A simplified collection method is the press-imprint-smear PIS.
PIS is considered a rapid and relatively sensitive method for the diagnosis of CL [ 11 ]. Parasite culture in tubes containing Novy-MacNeal-Nicolle medium from suspected lesions is difficult, requires significant technical expertise, is prone to contamination, and is time consuming [ 12 ]. The sensitivity of culture tends to be low and highly variable [ 13 ].
Recently developed mini- and micro-culture technologies have the advantage of being less costly because of the smaller volume of culture medium required, easier to use, and more sensitive, even when the parasite burden is low [ 12 ]. A disadvantage of micro-culture is that this technology does not allow for further species determination. In a recent study, the performance of micro-culture was assessed on subjects who fulfilled the criteria for CL.
Sensitivity and specificity for micro-culture were Additional advantages of this method are simplicity and the fact that diagnostic samples are retrieved by a needle-free method.
Current serologic tests for CL are mainly based on formats such as indirect fluorescent antibody, enzyme-linked immunosorbent assay ELISAwestern blot, lateral flow assay, and direct agglutination test.
However, these formats are not widely employed for the diagnosis of CL, because of the poor humoral response provoked by the infection and the consequential low sensitivity [ 915 ].
Furthermore, most currently available serologic tests are preliminary based on either a total parasite lysate or whole promastigote yielding in aspecific reactions. Recent developments suggest that incorporation of specific purified antigen preparations or recombinant Leishmania antigens for serologic diagnosis would increase the operational characteristics of these tests. This is following the success of the rK39 antigen for the sero-diagnosis of VL [ 16 ].
In addition, the cufanea had higher sensitivity than microscopy analysis. The test is currently being evaluated http: Patients with negative LST and diagnostic confirmation by other tests are more prone to relapse or treatment failure [ 1819 ]. The main disadvantages of the LST or MST are that it requires culture facilities to produce the MST antigen, that different antigen preparations impact test sensitivity, and that the test does not distinguish between past and present lsishmaniasis [ 20 ].
Many molecular diagnostic tests have been developed for the diagnosis of CL, as these are assumed to have better sensitivity and specificity than traditional diagnostic methods and allow the use of less invasive sampling for diagnosis [ 2324 ].
In particular PCR, either as a single test or in a cutnea format or as a quantitative assay, has been widely exploited. Numerous tests targeting many different gene sequences have been developed over the last decades, with the ribosomal DNA internal transcribed spacer 1 sequence [ 25 — 27 ], or sequences within the kinetoplast DNA of Leishmania genus as the main targets [ 2829 ].
Next to this, several other PCR-like assays, such as a high-tech fluorescence resonance energy transfer based on a real-time assay [ 2330 ], or assays based on HSP70 or tryparedoxin peroxidase gene targets [ 3132 ] amongst many cutanex, are under evaluation.
As there are no defined general accepted protocols and almost each laboratory applies its own in-house method, a head-to-head comparison of the different PCR methods needs leishmanniasis be undertaken. In particular, studies addressing inter-laboratory comparisons are scarce and the initiative by Cruz and co-workers [ 24 ] who proposed a protocol for inter-laboratory comparisons of conventional and real-time PCR methods should be taken on.
PCR requires adequate infrastructure and technically skilled operators, making tests cutanfa on this platform less suitable for resource-restricted laboratories in disease-endemic countries. In an attempt to partly circumvent these requirements, isothermal diagnostic platforms have been developed in recent years.
Nucleic acid sequence-based amplification, an isothermal reaction targeting parasite RNA, has been developed for leishmaniasis [ 33 ]. Oligo-chromatography for post-amplification analysis further circumvents the use of complex equipment while preserving appropriate diagnostic performance characteristics [ 213435 ]. Importantly, the specificity of the reaction is high because it uses six primers and the end product can be visualized directly using simple detection methods [ 36 ].
Amplification was visualized by the pre-amplification addition of fluorescent detection reagent and a simple ultraviolet lamp.
Different research groups further developed this technology for various applications [ 37 — 39 ]. The application of LAMP on boiled swab samples is an interesting advance to develop a simple and rapid point-of-care diagnostic method for CL [ 4041 ]. This approach has the potential advantages of using LAMP as a molecular diagnostic test in endemic regions where medical resources are limited.
Non-invasive sampling for Leishmania detection is essential for quick and affordable diagnosis. However, a significant variation in clinical accuracy of molecular diagnostic methods for CL is commonly observed, depending on the sample source, the method of DNA recovery, and the molecular test, and only a few attempts have been made to compare these variables [ 42 ]. Adams and co-workers evaluated two swab and aspirate samples from lesions of patients with suspected CL alongside standard diagnosis by microscopic detection of leishmaniqsis or culture of parasites from lesion material.
This method is minimally invasive for patients, easy to handle for medical personnel, and can easily be transported for analysis [ 4344 ]. Recently, other body samples, such as conjunctival swabs, are being considered as a source for CL tests but will require further research [ 4546 ]. Under a light microscope, all Leishmania species are morphologically undistinguishable from each other, yet species or strain identification is very relevant for patient management see next paragraph [ 547 ].
For several decades, isoenzyme analysis of Leishmania has been used for strain typing and this has allowed the construction of phylogenetic classifications [ 48 ], and even the differentiation between antroponotic and zoonotic variants within a single species [ 49 ]. This leishmsniasis is based on variation in the electrophoretic mobility of enzymes isolated from Leishmania parasites. Strains are consigned to various zymodemes. This highly specialized method is performed in a few reference laboratories only, because leishmqniasis is costly, time consuming, and requires large quantities of cultured promastigotes [ 50 ].
Therefore, alternative typing methods are being developed, in particular, based on genetic characteristics of the parasite. PCR-based methods in combination with restriction fragment length polymorphism analysis or sequencing enable correct species discrimination.
Over the last decade, several gene targets have been identified for this purpose. A widely employed target is the mini-exon gene, which is involved in the trans-splicing process of cuhanea messenger RNA, and is present as — tandem repeated copies per nuclear genome.
Each repeat consists of three major parts that make the mini-exon an excellent genotyping marker [ 51 ].
Leishmaniasis cutánea y mucosa
Marfurt and coworkers [ 5152 ] have developed a widely used typing technology comprising a PCR assay amplifying all the mini-exon sequences in a single reaction using universal primers, allowing preliminary discrimination between the major complexes i.
This methodology is now widely employed as a high-resolution, sensitive, and specific tool that can identify all clinically relevant Leishmania species [ 553 — 55 ]. Alternative candidate genes for typing are HSP70, hexokinase, and phosphoglucomutase genes for several Old World species [ 50 ] and HSP70 gene regions for New World species [ 5657 ].
HSPbased species identification tools cutahea potentially globally applicable in different clinical and sampling contexts, and they could become the reference method for identification of Leishmania species in clinical specimens [ 58 ].
In many low-resource settings, CL is diagnosed without laboratory confirmation tests, and a probable CL case has to be identified based solely on the patient history and physical examination.
Risk leishmaniaeis for CL to be addressed during history taking are: Physical signs lejshmaniasis for CL are crustaceous ulcerative lesions on unexposed areas such as the extremities and leisgmaniasis, the presence of satellite lesions Fig.
In the case of MCL, the involvement of mucosal tissue in the ear, nose, and throat tract should be excluded. Gold mining in West Suriname.
A gold digger garimpeiros at work in cuanea highly leishmaniasis-endemic area, Benzdorp, district Sipaliwini, in Suriname.