ORCID Profile
0000-0001-6741-3908
Current Organisation
The Kirby Institute
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Publisher: Elsevier BV
Date: 08-2018
Publisher: Public Library of Science (PLoS)
Date: 07-03-2022
DOI: 10.1371/JOURNAL.PNTD.0010238
Abstract: 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 either reduce the use of antimonials with the associated toxicities, or to increase efficacy. Here, we report the results of a recently completed trial assessing the efficacy and safety of a combination of thermotherapy (TT) plus a short course of miltefosine (MLT) for the treatment of uncomplicated CL in Colombia and Peru. A multicenter, randomized, evaluator-blinded, phase II, controled clinical trial was conducted. Adult volunteers with a parasitologically confirmed diagnosis of uncomplicated CL were randomly allocated to receive either a single session of TT or a combination of TT plus a short course of MLT (3 weeks). Therapeutic response outcomes and safety were assessed. 130 subjects were included in the study, of whom 64 were randomly assigned to the TT arm and 66 to the TT + MLT arm. Cure at 3 months’ follow-up was achieved in 57.8% (n = 37) and 80.3% (n = 53) in the TT and TT + MLT groups, respectively, in the intention to treat analysis. The TT + MLT regimen was better that TT alone (p = 0.0055). The presence of vesicles at the site of heat application was the most common adverse event reported associated with the use of TT while vomiting (31.8%) and elevation of liver enzymes (28.8%) were the most frequent adverse events reported associated with the use of MLT. The combination of TT plus a short course of MLT was shown to be significantly better than TT alone for the treatment of uncomplicated CL in the New World. Registered in clinicaltrials.gov NCT02687971 .
Publisher: Public Library of Science (PLoS)
Date: 02-05-2013
Publisher: MDPI AG
Date: 21-06-2023
DOI: 10.3390/V15071408
Abstract: All four serotypes of the dengue virus (DENV1–4) cause a phenotypically similar illness, but serial infections from different serotypes increase the risk of severe disease. Thus, genomic surveillance of circulating viruses is important to detect serotype switches that precede community outbreaks of disproportionate magnitude. A phylogenetic analysis was conducted on near full length DENV genomes sequenced from serum collected from a prospective cohort study from the Colombo district, Sri Lanka during a 28-month period using Oxford nanopore technology, and the consensus sequences were analyzed using maximum likelihood and Bayesian evolutionary analysis. From 523 patients, 328 DENV sequences were successfully generated (DENV1: 43, DENV2: 219, DENV3:66). Most circulating sequences originated from a common ancestor that was estimated to have existed from around 2010 for DENV2 and around 2015/2016 for DENV1 and DENV3. Four distinct outbreaks coinciding with monsoon rain seasons were identified during the observation period mostly driven by DENV2 cosmopolitan genotype, except for a large outbreak in 2019 contributed by DENV3 genotype I. This serotype switch did not result in a more clinically severe illness. Phylogeographic analyses showed that all outbreaks started within Colombo city and then spread to the rest of the district. In 2019, DENV3 genotype I, previously, rarely reported in Sri Lanka, is likely to have contributed to a disease outbreak. However, this did not result in more severe disease in those infected, probably due to pre-existing DENV3 immunity in the community. Targeted vector control within Colombo city before anticipated seasonal outbreaks may help to limit the geographic spread of outbreaks.
Publisher: Elsevier BV
Date: 03-2010
Publisher: Springer International Publishing
Date: 13-10-2017
Publisher: American Chemical Society (ACS)
Date: 31-03-2022
Publisher: American Society for Microbiology
Date: 02-2012
DOI: 10.1128/JCM.05061-11
Abstract: We present an algorithm based on three PCR assays for Leishmania ( Viannia ) species identification and assessed its performance using 70 specimens from Peruvian patients. The succession of the assayed targets can be ordered according to species prevalence. Sequential progression through the algorithm reduced the number of s les here studied by approximately 30% after each step.
Publisher: Public Library of Science (PLoS)
Date: 21-11-2012
Publisher: Elsevier BV
Date: 03-2010
Publisher: Springer Science and Business Media LLC
Date: 23-10-2020
DOI: 10.1038/S41598-020-75374-1
Abstract: Current methods for dengue virus (DENV) genome lification, lify parts of the genome in at least 5 overlapping segments and then combine the output to characterize a full genome. This process is laborious, costly and requires at least 10 primers per serotype, thus increasing the likelihood of PCR bias. We introduce an assay to lify near full-length dengue virus genomes as intact molecules, sequence these licons with third generation “nanopore” technology without fragmenting and use the sequence data to differentiate within-host viral variants with a bioinformatics tool (Nano-Q). The new assay successfully generated near full-length licons from DENV serotypes 1, 2 and 3 s les which were sequenced with nanopore technology. Consensus DENV sequences generated by nanopore sequencing had over 99.5% pairwise sequence similarity to Illumina generated counterparts provided the coverage was 100 with both platforms. Maximum likelihood phylogenetic trees generated from nanopore consensus sequences were able to reproduce the exact trees made from Illumina sequencing with a conservative 99% bootstrapping threshold (after 1000 replicates and 10% burn-in). Pairwise genetic distances of within host variants identified from the Nano-Q tool were less than that of between host variants, thus enabling the phylogenetic segregation of variants from the same host.
Publisher: Elsevier BV
Date: 02-2019
Publisher: Elsevier BV
Date: 03-2021
Publisher: Elsevier BV
Date: 04-2014
Publisher: Elsevier BV
Date: 08-2018
Publisher: Elsevier
Date: 2013
Publisher: Elsevier BV
Date: 04-2014
Publisher: Wiley
Date: 04-2020
DOI: 10.1111/JDV.16111
Publisher: American Society of Tropical Medicine and Hygiene
Date: 05-04-2011
Publisher: Wiley
Date: 31-10-2018
DOI: 10.1111/CUP.13369
Publisher: Elsevier BV
Date: 04-2014
Publisher: Informa UK Limited
Date: 26-11-2018
Publisher: Elsevier BV
Date: 2023
Publisher: Elsevier BV
Date: 08-2018
Publisher: American Society of Tropical Medicine and Hygiene
Date: 05-02-2020
Publisher: Public Library of Science (PLoS)
Date: 27-10-2011
Publisher: American Chemical Society (ACS)
Date: 03-07-2014
DOI: 10.1021/NL501884G
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 11-2017
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.DIAGMICROBIO.2012.06.010
Abstract: The heat-shock protein 70 gene (hsp70) has been exploited for Leishmania species identification in the Old and New World, using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism analysis. Three new Leishmania-specific hsp70 PCRs were recently described, and we applied 2 of these on 89 clinical s les from a total of 73 Peruvian patients with either cutaneous or mucocutaneous leishmaniasis. The new PCRs on average showed a 2- to 3-fold improved sensitivity in the tested s le types (lesion biopsies, aspirates, and scrapings), for both genus detection and species typing, and were most successful in biopsies. Leishmania braziliensis, L. peruviana, and L. guyanensis were encountered. About one third of the L. braziliensis parasites contained 2 hsp70 alleles. This study is a paradigm for the implementation of a globally applicable upgraded tool for the identification of Leishmania directly on human specimens from cutaneous and mucocutaneous lesions in the New World.
Publisher: American Society of Tropical Medicine and Hygiene
Date: 06-01-2016
Publisher: SPIE
Date: 28-01-2015
DOI: 10.1117/12.2070999
Publisher: Springer Science and Business Media LLC
Date: 08-08-2021
Publisher: Oxford University Press (OUP)
Date: 2010
DOI: 10.1086/648730
Abstract: Traditional detection of Leishmania from ulcers involves collection of invasive specimens that cause discomfort, require technical expertise, and carry risks of invasive procedures. We compared traditional diagnostic methods with a molecular noninvasive filter paper-based method for the diagnosis of cutaneous leishmaniasis. Consecutive patients presenting to the Leishmania Clinic at Hospital Nacional Cayetano Heredia were enrolled. Polymerase chain reaction (PCR) was performed on lesion scrapings, aspirates, and filter paper impressions. The reference standard was any 2 of 5 tests positive: smear, aspirate culture, invasive-specimen PCR (scrapings and aspirates), filter paper PCR, and leishmanin skin test. Outcome measures were sensitivity and specificity. Leishmania speciation was performed by PCR-restriction fragment length polymorphism (RFLP) of positive specimens. Forty-five patients with 66 lesions were enrolled. Of 52 lesions diagnosed as cutaneous leishmaniasis, 50 were positive by PCR of invasive specimens versus 48 by PCR of filter papers (P=.930). Sensitivity and specificity of PCR on invasively obtained specimens were 94.2% (95% confidence interval [CI], 87.9%-100%) and 92.9% (95% CI, 79.4%-100%). Sensitivity and specificity of filter paper PCR were 92.3% (95% CI, 85.1%-99.5%) and 100%. Culture, smear, and leishmanin skin test all had inferior sensitivities, compared with PCR of invasive or noninvasive specimens (P<.001). Of 50 specimens positive by PCR, 19 had sufficient DNA for PCR-RFLP analysis. Filter paper PCR constitutes a sensitive and specific alternative to traditional diagnostic assays. This novel, rapid, well-tolerated method has the potential for widespread use in the field and in pediatric populations where traditional specimen collection is most difficult to perform, and can potentially be used for rapid species identification.
Publisher: American Society of Tropical Medicine and Hygiene
Date: 03-04-2013
Publisher: Oxford University Press (OUP)
Date: 18-08-2017
Abstract: Species of the Leishmania Viannia (L. V.) subgenus harbor the double-stranded Leishmania RNA virus 1 (LRV-1), previously identified in isolates from Brazil and Peru. Higher levels of LRV-1 in metastasizing strains of L. V. guyanensis have been documented in both human and murine models, and correlated to disease severity. Expression of proinflammatory biomarkers, including interleukin (IL) 1β, tumor necrosis factor alpha (TNF-α), CXCL10, CCL5, IL-6, and superoxide dismutase, in human macrophages infected with 3 ATCC and 5 clinical isolates of L. V. braziliensis, L. V. guyanensis, and L. V. panamensis for 24 and 48 hours were measured by commercial enzyme immunoassay. Analyses were performed at 24 and 48 hours, stratified by LRV-1 status and species. LRV-1-positive L. V. braziliensis demonstrated significantly lower expression levels of TNF-α (P = .01), IL-1β (P = .0015), IL-6 (P = .001), and CXCL10 (P = .0004) compared with LRV-1-negative L. V. braziliensis. No differences were observed in strains of L. V. panamensis by LRV-1 status. Compared to LRV-1-negative L. V. braziliensis, LRV-1-positive strains of L. V. braziliensis produced a predominant Th2-biased immune response, correlated in humans to poorer immunologic control of infection and more severe disease, including mucosal leishmaniasis. Effects of LRV-1 on the pathogenesis of American tegumentary leishmaniasis may be species specific.
Publisher: Universidad Peruana Cayetano Heredia
Date: 06-07-2023
Abstract: Objetivos: Comparar la eficacia y toxicidad del antimoniato de meglumina (AM) y estibogluconato sódico (EGS) en el tratamiento de leishmaniasis cutánea (LC) en un hospital general. Material y métodos: Serie de casos comparativa de 193 pacientes con LC tratados en tres ensayos clínicos con AM (n=69) y EGS (n=124) durante 2001-2010. La administración de ambas drogas fue vía endovenosa lenta de 20 mg Sb5+/kg/día por 20 días consecutivos siguiendo las normativas de la OPS y OMS. La información clínica, toxicidad y eficacia fue obtenida de las historias clínicas almacenadas en el centro de investigación según la normativa local e internacional. Resultados: Las características demográficas fueron similares entre grupos, pero el tamaño y número de lesiones fueron mayores en el grupo AM. La eficacia del tratamiento con AM fue 76,0% versus 68,4% con EGS (p=0,340) y 55,1% versus 50,8% (p=0,570) en el análisis por protocolo y de intención de tratar, respectivamente. No se observaron efectos adversos inmediatos. Los síntomas más frecuentemente reportados fueron disgeusia (37,0%), mareos (32,0%), cefalea (36,0%), artralgias (31,0%) y linfangitis (21,0%). Los tres primeros síntomas, así como elevación de transaminasas, leucopenia, trombocitopenia y QTc prolongado fueron frecuentes en el grupo EGS, pero clínica y estadísticamente no significativos. El tratamiento fue suspendido definitivamente por toxicidad severa únicamente con EGS por emesis refractaria (2 participantes) y QTc prolongado con extrasístoles (1 participante). Conclusiones: La eficacia del tratamiento con AM y EGS fue comparable. La administración endovenosa de ambos no produjo efectosadversos inmediatos, aunque sí alteraciones clínicas y laboratoriales usuales.
Publisher: IEEE
Date: 08-2012
Publisher: American Society for Microbiology
Date: 03-2011
DOI: 10.1128/JCM.02457-10
Abstract: We compared traditional cutaneous leishmaniasis diagnostic methods to filter paper lesion impression (FPLI) PCR for secondarily infected ulcers and nonulcerative lesions. The sensitivity and specificity of FPLI PCR for secondarily infected lesions ( n = 8) were 100%. In primarily nonulcerative lesions ( n = 15), the sensitivity of FPLI PCR was inferior to that of pooled-invasive-specimen PCR (72.7% versus 100%) ( P = 0.10). FPLI PCR is sensitive, specific, and unlike invasive procedures, can be used in secondarily infected ulcers. Invasive specimen collection is superior in nonulcerative lesions.
Publisher: American Society of Tropical Medicine and Hygiene
Date: 05-08-2010
Publisher: Public Library of Science (PLoS)
Date: 23-07-2015
Publisher: Elsevier BV
Date: 08-2018
Publisher: Public Library of Science (PLoS)
Date: 28-01-2022
DOI: 10.1371/JOURNAL.PNTD.0010162
Abstract: American Tegumentary Leishmaniasis (ATL) is an endemic and neglected disease of South America. Here, mucosal leishmaniasis (ML) disproportionately affects up to 20% of subjects with current or previous localised cutaneous leishmaniasis (LCL). Preclinical and clinical reports have implicated the Leishmania RNA virus-1 (LRV1) as a possible determinant of progression to ML and other severe manifestations such as extensive cutaneous and mucosal disease and treatment failure and relapse. However, these associations were not consistently found in other observational studies and are exclusively based on cross-sectional designs. In the present study, 56 subjects with confirmed ATL were assessed and followed out for 24-months post-treatment. Lesion biopsy specimens were processed for molecular detection and quantification of Leishmania parasites, species identification, and LRV1 detection. Among in iduals presenting LRV1 positive lesions, 40% harboured metastatic phenotypes comparatively 58.1% of patients with LRV1 negative lesions harboured metastatic phenotypes ( p = 0.299). We found treatment failure ( p = 0.575) and frequency of severe metastatic phenotypes ( p = 0.667) to be similarly independent of the LRV1. Parasite loads did not differ according to the LRV1 status (p = 0.330), nor did Leishmanin skin induration size (p = 0.907) or histopathologic patterns ( p = 0.780). This study did not find clinical, parasitological, or immunological evidence supporting the hypothesis that LRV1 is a significant determinant of the pathobiology of ATL.
Publisher: Springer Science and Business Media LLC
Date: 11-04-2019
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.FORSCIINT.2016.03.042
Abstract: Various age estimation techniques have been utilised in Australia to evaluate the age of in iduals who do not have documentation to determine legal majority/culpability. These age estimation techniques rely on the assessment of skeletal development as visualised in radiographs, CT scans, MRI or ultrasound modalities, and subsequent comparison to reference standards. These standards are not always population specific and are thus known to be less accurate when applied outside of the original reference s le, leading to potential ethical implications. Therefore, the present study aims to: (i) explore the variation in developmental trajectories between the established Tanner-Whitehouse (TW) age estimation standards and a Western Australian population and (ii) develop specific hand-wrist age estimation standards for the latter population. The present study examines digital anterior-posterior hand-wrist radiographs of 360 in iduals 0 to 24.9 years of age, equally represented by sex. Each radiograph was assessed using the RUS, Carpal and 20-bone methods of Tanner et al. The standard error of the estimate (SEE) was calculated for each method (range: ♀ SEE ±0.4-11.5 years ♂ SEE ±0.9-10.1 years). The most accurate method was TW3 RUS for females and the TW2 Carpal system for males. The 50th centile skeletal maturity scores for each year age group were plotted against average chronological age to produce polynomial regression standards with a demonstrated accuracy of (♀ SEE ±0.09-3.46 years ♂ SEE ±0.02-3.42 years) for females and males, respectively. The standards presented here can be used in future forensic investigations that require age estimation of hand-wrist bones in a Western Australian population, however, they are not appropriate for establishing age of majority (18 years), as skeletal maturity was attained on average earlier than 15 years of age in both sexes for all three systems examined.
Publisher: Elsevier BV
Date: 08-2018
Publisher: American Society of Tropical Medicine and Hygiene
Date: 07-03-2018
Start Date: 2016
End Date: 2018
Funder: Consejo Nacional de Ciencia y Tecnología
View Funded ActivityStart Date: 2012
End Date: 2017
Funder: Fogarty International Center
View Funded ActivityStart Date: 2016
End Date: 2018
Funder: University of Alabama
View Funded Activity