What are the classical leishmaniasis treatment?
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Classical treatments for leishmaniasis, a neglected tropical disease caused by protozoan parasites of the genus *Leishmania*, have primarily relied on a limited range of drugs, which, despite their efficacy, present significant challenges including toxicity, resistance, and the need for parenteral administration. Pentavalent antimony compounds, such as meglumine antimoniate and sodium stibogluconate, have been the cornerstone of leishmaniasis treatment for decades. These drugs are used across the different clinical presentations of the disease, including cutaneous, mucocutaneous, and the more severe visceral leishmaniasis. However, the treatment with these antimonials is often long-term and associated with adverse events, drug resistance, and toxicity, which complicates the management of the disease. In response to these challenges, alternative drugs and treatment regimens have been explored. Miltefosine, an oral agent, emerged as a significant advancement in the treatment of leishmaniasis, showing potent leishmanicidal activity and offering a safer and more convenient treatment option compared to traditional therapies. It has been effective in treating all major clinical presentations of leishmaniasis, with high cure rates and a manageable side effect profile. Additionally, amphotericin B, pentamidine, and paromomycin are considered second-choice drugs due to their efficacy in cases where resistance to antimonials is observed. The lipid formulations of amphotericin B, in particular, have been developed to reduce toxicity. Despite these advancements, the quest for new therapeutic options continues, driven by the limitations of current treatments, including their side effects, the emergence of drug resistance, and the need for less toxic and more accessible therapies. This has led to research into novel compounds, drug combinations, and alternative routes of administration, such as topical treatments and intralesional injections, to improve efficacy, reduce side effects, and enhance patient compliance.
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| Papers (7) | Insight |
|---|---|
4 Citations | Classical treatment for cutaneous leishmaniasis includes intramuscular meglumine antimoniate. Alternative regimens like intralesional injections show less toxicity and can be effective, especially in cases with comorbidities. |
75 Citations | Classical treatment for leishmaniasis includes pentavalent antimony, which has reduced efficacy, administration challenges, and increased adverse events. Miltefosine is a new, effective, and safe oral treatment option. |
| Classical leishmaniasis treatments include various drugs with differences in cost, toxicity, and treatment duration. Newer options like immunotherapy and immunochemotherapy are also being explored for improved outcomes. | |
| Classical leishmaniasis treatments include systemic drugs with high toxicity. The paper discusses the shift towards effective topical formulations for cutaneous/mucocutaneous leishmaniasis treatment, offering advantages like improved compliance and reduced costs. | |
21 Citations | Classical treatments for leishmaniasis include outdated drugs with serious side effects and potential resistance issues, highlighting the need for new therapeutic options from natural sources. |
11 Citations | Classical leishmaniasis treatments include drugs with severe side effects. Traditional communities use local plants as alternative medicines, with leaves being the most commonly used part. |
| Classical leishmaniasis treatments include antimonials, which are first-choice drugs but limited by toxicity and resistance. Alternative options like amphotericin B, pentamidine, and miltefosine are used as second-choice drugs. |
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Amphotericine b treatment leishmaniasis new world5 answersAmphotericin B is an effective treatment for leishmaniasis, with varying doses showing different outcomes. Research suggests that doses between 7.5 mg/kg to 10 mg/kg are effective in reducing lesion size and parasite load without significant toxicity in BALB/c mice infected with L. amazonensis. However, higher doses, such as 12.5 mg/kg, while more effective, can lead to unacceptable toxicity. In cases of treatment failure with standard doses, increasing the dose of liposomal-amphotericin B has shown success in treating cutaneous leishmaniasis. Additionally, a microneedle-based delivery approach for amphotericin B has shown promise in treating small nodules caused by L. mexicana, although further optimization is needed for disseminated L. major infections.
What are the typical methods to control leishmania transmittion?4 answersControlling the transmission of Leishmania, a protozoan parasite causing leishmaniasis, involves a multifaceted approach targeting both the vector (sand flies) and the reservoir hosts (mainly dogs in the case of Leishmania infantum). One primary method is the use of topical insecticides (collars, spot-on treatments, and sprays) on dogs, which has demonstrated efficacy in reducing the incidence and prevalence of L. infantum by decreasing the odds of seroconversion in humans and dogs in endemic areas. Additionally, vaccination of dogs against Leishmania has proven to be an effective control tool, although the challenge of distinguishing vaccinated from naturally infected individuals remains.
Vector control strategies also include residual spraying of dwellings and animal shelters, the use of insecticide-treated nets, and the application of repellents or insecticides to skin or fabrics. However, the effectiveness of residual spraying may be limited in rural areas due to logistical challenges and the presence of large, untargeted reservoir populations of sand flies. Impregnated bed nets may offer a viable solution in areas where transmission occurs mainly indoors.
Emerging strategies involve innovative approaches such as paratransgenic manipulation of sand flies using commensal bacteria to render them refractory to Leishmania infection, and genetic modification of sand flies to inhibit pathogen transmission. Additionally, systemic control methods that target the vector-host interaction point by treating reservoir hosts with insecticide-treated food have shown promise in reducing the prevalence of infected sand fly females.
Nanotechnology is being explored for its potential to improve drug delivery for leishmaniasis treatment, with lipid-, polymer-, and metal-based nanocarriers showing promise in enhancing drug bioavailability and reducing toxicity. This approach, alongside the development of new drugs and delivery devices, is crucial given the limitations of current treatments, including drug resistance and clinical failure.
In summary, controlling Leishmania transmission requires a combination of direct interventions targeting the reservoir hosts, vector control measures, and the development of novel treatment and prevention strategies.
What are the disadvantages of present leishmaniasis treatment?4 answersThe current treatment landscape for leishmaniasis is fraught with several significant disadvantages that compromise its effectiveness and accessibility. Firstly, the limited arsenal of drugs available, including pentavalent antimonials, amphotericin B and its formulations, miltefosine, paromomycin sulphate, and pentamidine isethionate, are associated with high toxicity, which poses a substantial risk to patients' health. This toxicity, alongside the difficult administration routes and low efficacy of these drugs, underscores the urgent need for novel antileishmanial compounds. Furthermore, the existing treatments often require prolonged parenteral administration, which complicates patient adherence and increases the likelihood of developing drug-resistant strains.
The emergence of drug-resistant parasites, particularly to antimony compounds, amphotericin B, and miltefosine, has been documented and presents a significant challenge to controlling the disease. This resistance is exacerbated by the genetic variability and genome plasticity of the parasites, making the search for new drugs even more challenging. Additionally, the current chemotherapeutic treatments are outdated, associated with cytotoxicity and resistance, and their efficacy is hindered by the lack of understanding of leishmanial pathogenesis and the absence of a prophylactic vaccine.
The high cost and severe side effects of the few available drugs further limit their use, especially in neglected populations that are most affected by leishmaniasis. Rates of treatment failure are high, and the therapeutic failure of leishmaniasis is a serious concern, often linked to drug resistance in some areas. Given these drawbacks, there is a clear and pressing need for the development of new therapeutic approaches that are efficacious, less toxic, cost-effective, and easy to administer to effectively combat leishmaniasis.
What are the most common vectors for the transmission of Leishmania parasites?4 answersThe most common vectors for the transmission of Leishmania parasites, which cause a spectrum of diseases collectively known as leishmaniasis, are phlebotomine sand flies. Specifically, the genomes of two significant sand fly species, Phlebotomus papatasi and Lutzomyia longipalpis, have been sequenced to understand their roles in transmitting Leishmania parasites, including those causing cutaneous and visceral leishmaniasis. These vectors are of global significance, transmitting more than 40 pathogenic Leishmania species across 98 countries.
Machine learning models have identified that synanthropic sandflies living in areas with greater canopy height, less human modification, and within an optimal range of rainfall are more likely to be Leishmania vectors, suggesting environmental factors play a role in vector distribution. Additionally, the biology, distribution, and life cycle of sand flies, including their blood-feeding process and interactions with Leishmania parasites, are crucial for understanding their vectorial capacity.
Recent studies have also explored the potential of other arthropods in transmitting Leishmania parasites. For instance, biting midges of the genus Culicoides have been shown to transmit Leishmania parasites of the subgenus Mundinia, suggesting they could be potential vectors for these specific Leishmania species. However, sandflies remain the principal vector for the transmission of Leishmania infantum, which causes leishmaniosis in European cats and dogs and has zoonotic potential.
Experimental studies have demonstrated the vector competence of Lutzomyia longipalpis for Leishmania species other than L. infantum, indicating the adaptability and broad vectorial capacity of this sand fly species. Furthermore, the detection of Leishmania DNA in various sand fly species in Brazil underscores the complexity of vector-parasite interactions and suggests multiple vectors may be involved in the transmission cycle within specific regions.
Lastly, while vertical transmission of leishmaniasis has been documented, particularly in the absence of vector transmission, sand flies remain the primary mode of transmission for Leishmania parasites. Understanding the development and life cycle of Leishmania within sand flies is crucial for controlling the spread of leishmaniasis.