Byron Arana

Drugs for Neglected Diseases Initiative | DNDi · NTD

Cutaneous leishmaniasis (CL), caused by protozoan parasites of the Leishmania genus, is prevalent in tropical and subtropical regions, with important morbidity, particularly in low- to middle-income countries. Current systemic treatments, including pentavalent antimonials and miltefosine, are associated with significant toxicity, reduced efficacy,...

Background Cutaneous leishmaniasis (CL) is a parasitic vector borne disease endemic in 90 countries, including Guatemala. Despite the endemicity of the disease in the country, the most important factors that contribute to its transmission remain unknown. To address these knowledge gaps, we characterized the sand fly populations and Leishmania paras...

Background Target Product Profiles (TPPs) are instrumental to help optimise the design and development of therapeutics, vaccines, and diagnostics – these products, in order to achieve the intended impact, should be aligned with users’ preferences and needs. However, patients are rarely involved as key stakeholders in building a TPP. Methodology Th...

Cutaneous leishmaniasis (CL) is a parasitic vector-borne disease affecting mostly low- and middle-income coun- tries. CL is endemic in Guatemala, where an increase in the number of cases and incidence and a changing dis- ease distribution in the past decade have been reported. Important research was conducted in Guatemala in the 1980s and 1990s to...

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 ye...

Background Systemic pentavalent antimonials, mainly meglumine antimoniate, continue to be the first-choice drugs for treatment of cutaneous leishmaniasis (CL) despite their toxicity, difficulty of administration and high cost. In the search for therapeutic alternatives, combining two treatment interventions has emerged as a potential alternative to...

Cutaneous leishmaniasis (CL) affects the lives of 0.7–1 million people every year causing lesions that take months to heal. These lesions can result in disfiguring scars with psychological, social and economic consequences. Antimonials are the first line of therapy for CL, however the treatment is lengthy and linked to significant toxicities; furth...

Background Cutaneous leishmaniasis (CL) is a disease that often affects exposed skin areas and may heal leaving lifelong scars. Patients’ expectations from treatment are rarely considered in drug development for CL. An initiative aiming to address shortcomings in clinical trial design and conduct for CL treatments involving the researchers’ communi...

Although there have been significant advances in the treatment of visceral leishmaniasis (VL) and several novel compounds are currently in pre-clinical and clinical development for this manifestation of leishmaniasis, there have been limited advances in drug research and development (R & D) for cutaneous leishmaniasis (CL). Here we review the need...

Objectives Localized cutaneous leishmaniasis and its evolving forms diffuse cutaneous leishmaniasis, mucosal leishmaniasis and cutaneous leishmaniasis recidivans, together with the visceral leishmaniasis sequelae post-kala azar dermal leishmaniasis account for about one million dermal leishmaniases cases per year worldwide. Although not lethal, the...

Research in visceral leishmaniasis in the last decade has been focused on how better to use the existing medicines as monotherapy or in combination. Systematic research by geographical regions has shown that a universal treatment is far from today's reality. Substantial progress has been made in the elimination of kala-azar in South Asia, with a cl...

Background Pentavalent antimonials (Sb5) are the first-line drugs for treating cutaneous leishmaniasis in Colombia; however, given problems with toxicity, compliance, availability, and cost, it is imperative to look for better therapeutic options. Intravenous amphotericin B (AmB) has been used extensively to treat visceral leishmaniasis; however, e...

Consolidated Standards of Reporting Trials (CONSORT) checklist. (PDF)

Introduction Lack of investments in drug development, lack of standardisation of clinical trials and the complexity of disease presentations contribute to the current lack of effective, safe and adapted treatments for cutaneous leishmaniasis (CL). One aspect concerns outcomes affecting patients’ quality of life (QoL): these are hardly assessed in t...

Introduction Progress with the treatment of cutaneous leishmaniasis (CL) has been hampered by inconsistent methodologies used to assess treatment effects. A sizable number of trials conducted over the years has generated only weak evidence backing current treatment recommendations, as shown by systematic reviews on old-world and new-world CL (OWCL...

For human health, leishmaniasis is among the most important protozoan diseases, superseded only by malaria. Globally, 10 to 12 million people are infected with 1.5 million new cases every year. The development of cheaper new drugs is urgently needed for this neglected disease that is developing resistance to current treatments. Chemotherapy remains...

For human health, leishmaniasis is among the most important protozoan diseases, superseded only by malaria. Globally, 10 to 12 million people are infected with 1.5 million new cases every year. The development of cheaper new drugs is urgently needed for this neglected disease that is developing resistance to current treatments. Chemotherapy remains...

Background The South-East Asia Region Kala-azar Elimination Programme (KAEP) is expected to enter the consolidation phase in 2017, which focuses on case detection, vector control, and identifying potential sources of infection. Post-kala-azar dermal leishmaniasis (PKDL) is thought to play a role in the recurrence of visceral leishmaniasis (VL)/kala...

Background The decade following the Regional Strategic Framework for Visceral Leishmaniasis (VL) elimination in 2005 has shown compelling progress in the reduction of VL burden in the Indian subcontinent. The Special Programme for Research and Training in Tropical Diseases (TDR), hosted by the World Health Organization (WHO) and other stakeholders,...

WHO TDR–funded and/or WHO TDR–supported drug development research towards elimination of visceral leishmaniasis in the Indian subcontinent. Abbreviations: TDR, Special Programme for Research and Training in Tropical Diseases; WHO, World Health Organization. (DOCX)

Background: As Bangladesh, India and Nepal progress towards visceral leishmaniasis (VL) elimination, it is important to understand the role of asymptomatic Leishmania infection (ALI), VL treatment relapse and post kala-azar dermal leishmaniasis (PKDL) in transmission. Methodology/ principal finding: We reviewed evidence systematically on ALI, re...

Supplementary information containing unpublished information (Tables A, B, C, J and K), PRISMA statement (Table D), Strategies and keywords used for literature search (Table E), Potential risk of bias in studies (Tables F to I), and Modelling transmission of Leishmania donovani infection in the Indian subcontinent (Table L). (DOCX)

Cutaneous Leishmaniasis (CL) is a tropical parasitic disease in humans, transmitted by sandflies. CL causes lesions on exposed parts of the body, potentially leaving life-long scars. The disease manifestations vary significantly, depending on parasite species. An estimated 0.7 - 1.3 million new cases occur worldwide annually. Recommendations on th...

Cutaneous leishmaniasis (CL) is endemic in the northern region of Guatemala reporting a prevalence of less than 1%. The National Ministry of Health (NMH) recognizes the challenges in underreporting and limitations in the care of patients, and has taken steps to improve surveillance by moving from a passive to active monitoring system in the last fi...

Now is a good time to reconsider research priorities as 2015 approaches, the target date originally set for elimination of visceral leishmaniasis. Visceral leishmaniasis is one of the most deadly parasitic diseases and disproportionately affects the poorest and most vulnerable populations. An estimated 200 000–400 000 people contract visceral leish...

Objectives: We identified barriers to care seeking for pneumonia and diarrhea among rural Guatemalan children. Methods: A population-based survey was conducted twice from 2008 to 2009 among 1605 households with children younger than 5 years. A 14-day calendar recorded episodes of carer-reported pneumonia (n = 364) and diarrhea (n = 481), and for...

For the treatment of visceral leishmaniasis in Bangladesh, single dose liposomal amphotericin B (ambisome) is supposed to be the safest and most effective treatment. Specific needs for application and storage raise questions about feasibility of its implementation and acceptance by patients and health staff. Methods. The study was carried out in th...

Background: To rapidly reduce the burden of visceral leishmaniasis for national elimination programmes, an acceptable, safe, and effective treatment is needed that can be delivered at primary health-care centres. We aimed to assess the tolerability, safety, and cure rate of single-dose liposomal amphotericin B (AmBisome, Gilead, USA) for visceral l...

The current evidence-base for recommendations on the treatment of cutaneous leishmaniasis (CL) is generally weak. Systematic reviews have pointed to a general lack of standardization of methods for the conduct and analysis of clinical trials of CL, compounded with poor overall quality of several trials. For CL, there is a specific need for methodol...

Background Active case detection (ACD) significantly contributes to early detection and treatment of visceral leishmaniasis (VL) and post kala-azar dermal leishmaniasis (PKDL) cases and is cost effective. This paper evaluates the performance and feasibility of adapting ACD strategies into national programs for VL elimination in Bangladesh, India an...

Objective: Standard treatment of Indian post-kala-azar dermal leishmaniasis (PKDL) is unsatisfactory because to achieve therapeutic effectiveness, heroic courses of parenteral and toxic agents have to be administered. Our objective was to evaluate oral miltefosine for its potential to provide effective as well as tolerable treatment for this disea...

Background In view of the epidemiological expansion of dengue worldwide and the availability of new tools and strategies particularly for controlling the primary dengue vector Aedes aegypti, an intervention study was set up to test the efficacy, cost and feasibility of a combined approach of insecticide treated materials (ITMs) alone and in combina...

Objectives: To investigate the changes of bacteriological index and leprosy reactions among Multi-bacillary (MB) patients treated with uniform multi-drug therapy (UMDT). Methods: Newly diagnosed leprosy patients were recruited after taking informed consent in three districts in Guizhou Province and one district in Yunnan Province China during No...

. National VL Elimination Programs in India, Nepal and Bangladesh face challenges as home-based Miltefosine treatment is introduced. Objectives . To study constraints of VL management in endemic districts within context of national elimination programs before and after intervention. Methods . Ninety-two and 41 newly diagnosed VL patients were inter...

Pneumonia causes more child deaths than does any other disease. Observational studies have indicated that smoke from household solid fuel is a significant risk factor that affects about half the world's children. We investigated whether an intervention to lower indoor wood smoke emissions would reduce pneumonia in children. We undertook a parallel...

Miltefosine (target dose of 2.5 mg/kg/day for 28 days) is the recommended treatment for visceral leishmaniasis (kala-azar) in Bangladesh on the basis of data from India. We evaluated miltefosine in a phase IV trial of 977 patients in Bangladesh. At the six-month final follow up, 701 were cured. 24 showed initial treatment failure, and 95 showed tre...

A large body of evidence suggests that fine particulate matter (PM) air pollution is a cause of cardiovascular disease, but little is known in particular about the cardiovascular effects of indoor air pollution from household use of solid fuels in developing countries. RESPIRE (Randomized Exposure Study of Pollution Indoors and Respiratory Effects)...

The world's burden of infectious diseases can be substantially reduced by more-effective use of existing interventions. Advances in case detection, diagnosis, and treatment strategies have made it possible to consider the elimination of visceral leishmaniasis in the Indian subcontinent. The priority must now be to effectively implement existing int...

The combination of one intravenous administration of 5mg/kg Ambisome and oral administration of miltefosine, 2.5mg/kg/day for 14 days, was evaluated in 135 Indian patients with kala-azar. The Intent-to-Treat cure rate at 6 months was 124 of the 135 enrolled patients (91.9%: 95% CI = 86-96%), and the per protocol cure rate was 124 of 127 evaluable p...

Pharmacovigilance is concerned with the assessment of benefit and harm. Disease burden, status of healthcare delivery through government centres and practitioners, existing pharmacovigilance programmes, relevant pre-marketing studies and the likely effectiveness and risks of drugs must be considered for planning pharmacovigilance activity. The risk...

Background: The promotion of point-of-use water treatment and handwashing with soap has led to large reductions in child diarrhea in randomized efficacy trials. We know little about the sustainability of behavior change and health benefits after the conclusion of intervention activities. Methods: We present an extension of previously published de...

Onchocerciasis (river blindness), which is close to being eliminated from Guatemala through semiannual administration of ivermectin, is still transmitted in one area of the country that coincidentally receives an annual influx of migrant workers to harvest coffee. Migrant workers generally are not included in semiannual ivermectin treatments, but i...

The promotion of household water treatment and handwashing with soap has led to large reductions in child diarrhoea in randomized efficacy trials. Currently, we know little about the health effectiveness of behaviour-based water and hygiene interventions after the conclusion of intervention activities. We present an extension of previously publishe...

Exposure to household wood smoke from cooking is a risk factor for chronic obstructive lung disease among women in developing countries. The Randomized Exposure Study of Pollution Indoors and Respiratory Effects (RESPIRE) is a randomized intervention trial evaluating the respiratory health effects of reducing indoor air pollution from open cooking...

Indoor air pollution from burning of biomass fuel in open fires is a known risk factor for chronic obstructive pulmonary disease (COPD) in developing countries. To estimate the prevalence of respiratory symptoms and lung function among women in rural Guatemala and to describe the methods and practical issues associated with the assessment of respir...

Endosymbionic Wolbachia bacteria inside adult Onchocerca volvulus worms (causing river blindness) are necessary for female worm fertility. We evaluated whether rifampin and/or azithromycin used in a five-day course could kill Wolbachia. In an open-label trial in Guatemala, 73 patients with 134 palpable onchocercal nodules were randomized into four...

To eliminate transmission of Onchocerca volvulus, semiannual mass treatment with ivermectin (Mectizan; donated by Merck & Co) has been underway in Guatemala since 2000. We applied the 2001 World Health Organization (WHO) elimination criteria in the Santa Rosa focus of onchocerciasis transmission in Guatemala (10,923 persons at risk). No evidence of...

Trials of environmental risk factors and acute lower respiratory infections (ALRI) face a double challenge: implementing sufficiently sensitive and specific outcome assessments, and blinding. We evaluate methods used in the first randomized exposure study of pollution indoors and respiratory effects (RESPIRE): a controlled trial testing the impact...

OBJECTIVE: Trials of environmental risk factors and acute lower respiratory infections (ALRI) face a double challenge: implementing sufficiently sensitive and specific outcome assessments, and blinding. We evaluate methods used in the first randomized exposure study of pollution indoors and respiratory effects (RESPIRE): a controlled trial testing...

The polymerase chain reaction (PCR) assay has been reported for the diagnosis of cutaneous leishmaniasis (CL). Real-time (RT) PCR offers several advantages over traditional PCR, including faster processing time and decreased risk of contamination. Enhanced portability is another benefit that expands the applicability of the assay. A portable RT-PCR...

Indoor air pollution (IAP) from combustion of biomass fuels represents a global health problem, estimated to cause 1.6 million premature deaths annually. RESPIRE (Randomised Exposure Study of Pollution Indoors and Respiratory Effects) Guatemala is the first randomised controlled trial ever performed on health effects from solid fuel use. Its goal i...

World Health Organization certification criteria for onchocerciasis elimination use anterior segment eye lesion prevalence as an indicator of mass ivermectin treatment program success. Lesions either contain visible microfilaria (noninflammatory punctate keratitis [PK] or microfilariae in anterior chamber [MFAC]), or microfilaria obscured by inflam...

We have evaluated biopsies from patients with atypical nodular and typical ulcerated lesions of cutaneous leishmaniasis, from leishmanin reactions and skin from normal individuals from Nicaragua, Honduras and Guatemala for the presence of inorganic particles using confocal microscopy with a polarised light source and conventional histopathological...

Endosymbionic Wolbachia bacteria inside adult Onchocerca volvulus worms (causing river blindness) are necessary for female worm fertility. We evaluated whether rifampin and/or azithromycin used in a five-day course could kill Wolbachia. In an open-label trial in Guatemala, 73 patients with 134 palpable onchocercal nodules were randomized into four...