Publications by authors named "Nancy Saravia"

Unlabelled: Macrophages are the principal host cells of . in human infection and play a critical role in controlling infection and enabling parasite survival and persistence. Nevertheless, understanding of drug resistance in leishmaniasis has primarily focused on the parasite.

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  • - Neutrophils play a crucial role in fighting infections, but their function in drug-resistant infections, like leishmaniasis, is not well understood.
  • - Research shows that drug-resistant parasites change the expression of certain neutrophil genes, increasing detoxification processes and reducing cytokine production, particularly impacting a chemokine called CCL3.
  • - Reduced CCL3 levels hinder neutrophils’ ability to recruit other immune cells, which was confirmed in mouse models, highlighting how drug-resistant parasites can alter immune responses in infected skin.
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  • *2! It finds that parasite survival rates in various cell models can predict treatment success, with Sb-resistant strains being associated with higher odds of treatment failure and larger lesion sizes in mouse models.
  • *3! Host risk factors also complicate the interpretation of treatment outcomes, indicating that both parasite characteristics and patient conditions play critical roles in the effectiveness of leishmaniasis treatment.
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Research capacity is a critical component of pandemic preparedness, as highlighted by the challenges faced during the Ebola outbreak in West Africa. Recent global initiatives, such as the Research & Development Task Force of the Global Health Security Agenda and the World Health Assembly's resolution on strengthening clinical trials, emphasize the need for robust research capabilities. This Perspective discusses the experiences of leaders in infectious disease research and capacity building in low- and middle-income countries, focusing on Colombia, Jamaica, and Pakistan.

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  • Cutaneous leishmaniasis (CL) is a persistent global health issue with lengthy treatment and follow-up periods, leading to significant patient loss to follow-up and uncertainty about treatment effectiveness.
  • A study in rural Colombia tested a mobile health (mHealth) intervention to track treatment adherence, side effects, and patient outcomes, finding that it significantly improved follow-up rates from 4.2% to 82.5% compared to standard care.
  • Although patients and health workers found the app user-friendly and valuable for improving healthcare access, challenges like low connectivity impacted data transmission in real-time.
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Background: In Latin America, cutaneous leishmaniasis primarily affects dispersed rural communities, that have limited access to the public health system and medical attention. Mobile health (mHealth) strategies have shown potential to improve clinical management and epidemiological surveillance of neglected tropical diseases, particularly those of the skin.

Methods: The Guaral +ST app for Android was designed to monitor cutaneous leishmaniasis treatment and assess therapeutic response.

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Background: Treatment guidance for children and older adult patients affected by cutaneous leishmaniasis (CL) is unclear due to limited representation of these groups in clinical trials.

Methods: We conducted a collaborative retrospective study to describe the effectiveness and safety of antileishmanial treatments in children ≤ 10 and adults ≥ 60 years of age, treated between 2014 and 2018 in ten CL referral centers in Latin America.

Results: 2,037 clinical records were assessed for eligibility.

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  • A total of 73 patients were randomly assigned to receive either MA with PTX or MA with a placebo, and various metrics were evaluated, including therapeutic failure rates and inflammatory gene expression.
  • Results indicated no significant improvement in treatment efficacy with PTX, showing failure rates of 35% for PTX compared to 25% for placebo, and no change in inflammatory mediator expression linked to the treatment groups.
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  • Antimonial drugs and miltefosine often fail to effectively treat cutaneous leishmaniasis, prompting research into alternative oral combination therapies to boost treatment efficacy and prevent drug resistance.
  • In a study, posaconazole and itraconazole showed high potency against various Leishmania (Viannia) panamensis strains, while fluconazole and voriconazole were less effective.
  • The combination of miltefosine and posaconazole demonstrated significant synergy, leading to a greater reduction in infection when tested against clinical strains, indicating its potential as a new treatment strategy.
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  • Recent research shows that the body's natural immune response may play a role in how well antimicrobial drugs work, particularly against leishmaniasis.
  • The study focused on how clinical strains of parasites resistant to a common antileishmanial drug, pentavalent antimony (SbV), affect neutrophil activation by comparing sensitive and resistant strains.
  • The findings indicate that neutrophils infected with drug-resistant strains produce less reactive oxygen species and have a different expression profile for specific activation markers compared to those infected with drug-sensitive strains.
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The immune mechanisms that contribute to the efficacy of treatment of cutaneous leishmaniasis (CL) are not fully understood. The aim of this study was to define immune correlates of the outcome of treatment of CL caused by () species during standard of care treatment with pentavalent antimonials. We conducted a comparative expression profiling of immune response genes in peripheral blood mononuclear cells (PBMCs) and lesion biopsy specimens obtained from CL patients before and at the end of treatment (EoT) with meglumine antimoniate.

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is the main causative agent of cutaneous leishmaniasis in Colombia and is usually treated with either meglumine antimoniate (MA) or miltefosine (MIL). In recent years, there has been increasing evidence of the emergence of drug-resistance against these compounds. Neutrophils are known to play an important role in immunity against .

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Mobile applications (apps) can bring health research and its potential downstream benefits closer to underserved populations. Drawing on experience developing an app for detecting and referring cases of cutaneous leishmaniasis in Colombia, called Guaral/app, we review key steps in creating such mobile health (mHealth) tools. These require consideration of the sociotechnical context using methods such as systems analysis and human-centered design (HCD), predicated on engagement and iteration with all stakeholders.

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argue that development of research capacity in Latin America and the Caribbean requires investment in both individuals and regional institutions

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  • The study developed a population pharmacokinetic (PK) model to analyze how the antileishmanial drug miltefosine behaves inside peripheral blood mononuclear cells (PBMCs) in patients with cutaneous leishmaniasis.
  • The model used data from 339 plasma and 194 PBMC miltefosine concentrations in Colombian patients, finding that an intracellular-to-plasma concentration ratio of 2.17 is key for understanding drug distribution.
  • Results indicated that both plasma and intracellular exposure levels significantly influenced the probability of curing the infection, with a suggested target level of miltefosine that could greatly increase cure rates, particularly in children when a specific dosing approach is applied.
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A novel pan- loop-mediated isothermal amplification (LAMP) assay for the diagnosis of cutaneous and visceral leishmaniasis (CL and VL) that can be used in near-patient settings was developed. Primers were designed based on the 18S ribosomal DNA (rDNA) and the conserved region of minicircle kinetoplast DNA (kDNA), selected on the basis of high copy number. LAMP assays were evaluated for CL diagnosis in a prospective cohort trial of 105 patients in southwest Colombia.

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The pathological processes resulting from parasitic infection are known to have important impacts on the mother child dyad during pregnancy. The roles of parasite transmission and the maternal immune response have been described in diseases such as malaria, toxoplasmosis, and trypanosomiasis. However, the impact of parasites of the genus Leishmania, etiological agents of the neglected tropical diseases tegumentary leishmaniasis (TL) and visceral leishmaniasis (VL), is comparatively less well known, though it is an increasingly recognized concern for infected mothers and their fetuses.

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The mechanisms of Leishmania resistance to antimonials have been primarily determined in experimentally derived Leishmania strains. However, their participation in the susceptibility phenotype in field isolates has not been conclusively established. Being an intracellular parasite, the activity of antileishmanials is dependent on internalization of drugs into host cells and effective delivery to the intracellular compartments inhabited by the parasite.

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  • The study investigates why some patients still have the Leishmania parasite after they seem to be cured of cutaneous leishmaniasis (CL) following treatment.
  • Out of 70 patients treated with either meglumine antimoniate or miltefosine, 60% showed signs of parasite persistence at the end of treatment, with 30% still showing it 13 weeks later.
  • A previous episode of CL was found to help reduce the likelihood of detectable parasite persistence, raising questions about the role of lingering infections in disease spread and reactivation.
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  • A study compared the cost-effectiveness of miltefosine, taken at home under supervision, to the injectable treatment meglumine antimoniate (MA) for children with cutaneous leishmaniasis in southwest Colombia.
  • Results showed that miltefosine had a significantly lower cost-per-cure, costing $188 compared to $531 for MA from a societal perspective, and $30 compared to $442 from a patient's view.
  • However, from the government’s perspective, miltefosine was slightly more expensive ($158) than MA ($89), indicating different cost impacts depending on whose perspective is considered.
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Infection by () , the predominant etiologic agent for cutaneous leishmaniasis in Colombia, is characterized by a chronic mixed inflammatory response. Current treatment options are plagued by toxicity, lengthy treatment regimens, and growing evidence of drug resistance. Immunotherapy, modulating the immune system to mount a protective response, may provide an alternate therapeutic approach.

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  • A clinical trial was conducted in Colombia to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of miltefosine in children and adults with cutaneous leishmaniasis, enrolling 60 patients (30 children and 30 adults) who received 2.5 mg/kg/day for 28 days.
  • Results showed that while miltefosine was effective, 52 patients were cured, but treatment failed in 5 children and 3 were lost to follow-up, with a majority of the isolated strains showing resistance.
  • Findings indicated that miltefosine concentrations were generally lower in children than adults, which could affect treatment outcomes and suggest the need for adjusted therapeutic regimens for pediatric patients.
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Cutaneous and mucosal leishmaniasis is widely distributed in Central and South America. Leishmania of the Viannia subgenus are the most frequent species infecting humans. L.

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