ORCID Profile
0000-0002-8375-5542
Current Organisations
Universidade Federal do Rio Grande do Sul
,
University of Warwick
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Epigenetics (incl. Genome Methylation and Epigenomics) | Nanotechnology | Analytical Biochemistry | Nanobiotechnology |
Expanding Knowledge in the Biological Sciences | Expanding Knowledge in Technology
Publisher: Public Library of Science (PLoS)
Date: 11-07-2022
DOI: 10.1371/JOURNAL.PNTD.0010599
Abstract: Gambiense human African trypanosomiasis (gHAT) has been targeted for elimination of transmission (EoT) to humans by 2030. Whilst this ambitious goal is rapidly approaching, there remain fundamental questions about the presence of non-human animal transmission cycles and their potential role in slowing progress towards, or even preventing, EoT. In this study we focus on the country with the most gHAT disease burden, the Democratic Republic of Congo (DRC), and use mathematical modelling to assess whether animals may contribute to transmission in specific regions, and if so, how their presence could impact the likelihood and timing of EoT. By fitting two model variants—one with, and one without animal transmission—to the human case data from 2000–2016 we estimate model parameters for 158 endemic health zones of the DRC. We evaluate the statistical support for each model variant in each health zone and infer the contribution of animals to overall transmission and how this could impact predicted time to EoT. We conclude that there are 24/158 health zones where there is substantial to decisive statistical support for some animal transmission. However—even in these regions—we estimate that animals would be extremely unlikely to maintain transmission on their own. Animal transmission could h er progress towards EoT in some settings, with projections under continuing interventions indicating that the number of health zones expected to achieve EoT by 2030 reduces from 68/158 to 61/158 if animal transmission is included in the model. With supplementary vector control (at a modest 60% tsetse reduction) added to medical screening and treatment interventions, the predicted number of health zones meeting the goal increases to 147/158 for the model including animal transmission. This is due to the impact of vector reduction on transmission to and from all hosts.
Publisher: Cold Spring Harbor Laboratory
Date: 23-06-2020
DOI: 10.1101/2020.06.23.20138065
Abstract: Gambiense human African trypanosomiasis (gHAT) is a virulent disease declining in burden but still endemic in West and Central Africa. Although it is targeted for elimination of transmission by 2030, there remain numerous questions about the drivers of infection and how these vary geographically. In this study we focus on the Democratic Republic of Congo (DRC), which accounted for 84% of the global case burden in 2016, to explore changes in transmission across the country and elucidate factors which may have contributed to the persistence of disease or success of interventions in different regions. We present a Bayesian fitting methodology, applied to 168 endemic health zones (∼ 100,000 population size), which allows for calibration of mechanistic gHAT model to case data (from the World Health Organization HAT Atlas) in an adaptive and automated framework. It was found that the model needed to capture improvements in passive detection to match observed trends in the data within former Bandundu and Bas Congo provinces indicating these regions have substantially reduced time to detection. Health zones in these provinces generally had longer burn-in periods during fitting due to additional model parameters. Posterior probability distributions were found for a range of fitted parameters in each health zone these included the basic reproduction number estimates for pre-1998 ( R 0 ) which was inferred to be between 1 and 1.19, in line with previous gHAT estimates, with higher median values typically in health zones with more case reporting in the 2000s. Previously, it was not clear whether a fall in active case finding in the period contributed to the declining case numbers. The modelling here accounts for variable screening and suggests that underlying transmission has also reduced greatly – on average 96% in former Equateur, 93% in former Bas Congo and 89% in former Bandundu – Equateur and Bandundu having had the highest case burdens in 2000. This analysis also sets out a framework to enable future predictions for the country. Gambiense human African trypanosomiasis (gHAT sleeping sickness) is a deadly disease targeted for elimination by 2030, however there are still several unknowns about what factors influence continued transmission and how this changes with geographic location. In this study we focus on the Democratic Republic of Congo (DRC), which reported 84% of the global cases in 2016 to try and explain why some regions of the country have had more success than others in bringing down case burden. To achieve this we used a state-of-the-art statistical framework to match a mathematical gHAT model to reported case data for 168 regions with some case reporting during 2000–2016. The analysis indicates that two former provinces, Bandundu and Bas Congo had substantial improvements to case detection in fixed health facilities in the time period. Overall, all provinces were estimated to have reductions in (unobservable) transmission including ∼ 96% in former Equateur. This is reassuring as case finding effort has decreased in that region. The model fitting presented here will allow predictions of gHAT under future strategies to be performed in the future.
Publisher: Cold Spring Harbor Laboratory
Date: 04-07-2020
DOI: 10.1101/2020.07.03.20145847
Abstract: Gambiense human African trypanosomiasis (sleeping sickness, gHAT) is a disease targeted for elimination of transmission (EOT) by 2030. Despite the number of new cases reported annually being at a historical minimum, the likelihood of achieving EOT is unknown. We utilised modelling to study the impact of four strategies comprised of currently-available intervention methods including active and passive screening and vector control (VC) on transmission across 168 health zones in the Democratic Republic of the Congo. By estimating the median year of EOT and the probability of EOT by 2030 under each strategy, the model predicts only 81 health zones are on track to achieve the EOT target using medical-only strategies and this number drops to 52 when uncertainty is considered ( 90% probability). Although all health zones are predicted to meet EOT by 2030 under strategies with VC, blanket coverage is impractical so this analysis provides a priority list of health zones for consideration for supplementary VC implementation in conjunction with medical interventions.
Publisher: Cold Spring Harbor Laboratory
Date: 16-12-2021
DOI: 10.1101/2021.12.15.21267833
Abstract: Gambiense human African trypanosomiasis (gHAT) has been targeted for elimination of transmission (EoT) to humans by 2030. Whilst this ambitious goal is rapidly approaching, there remain fundamental questions about the presence of non-human animal transmission cycles and their potential role in slowing progress towards, or even preventing, EoT. In this study we focus on the country with the most gHAT disease burden, the Democratic Republic of Congo (DRC), and use mathematical modelling to assess whether animals may contribute to transmission in specific regions, and if so, how their presence could impact the likelihood and timing of EoT. By fitting two model variants – one with, and one without animal transmission – to the human case data from 2000–2016 we estimate model parameters for 158 endemic health zones of DRC. We evaluate the statistical support for each model variant in each health zone and infer the contribution of animals to overall transmission and how this could impact predicted time to EoT. We conclude that there are 24/158 health zones where there is moderate or high statistical support for some animal transmission. However, – even in these regions – we estimate that animals would be extremely unlikely to maintain transmission on their own. Animal transmission could h er progress towards EoT in some settings, with projections under continuing interventions indicating that the number of health zones expected to achieve EoT by 2030 reduces from 68 to 61 if animals are included in the model. With supplementary vector control (at a modest 60% tsetse reduction) added to medical screening and treatment interventions, the predicted number of health zones meeting the goal increases to 147/158 for the model including animals. This is due to the impact of vector reduction on transmission to and from all hosts. Elimination of African sleeping sickness by 2030 is an ambitious goal, not least because of the unclear role that animals might play in transmission. We use mathematical models, fitted to case data from DRC to assess and quantify the contribution of animals to the human case burden. We found that 24/158 geographic regions included in this study had statistical evidence of animal transmission, although it appears extremely unlikely that animals could maintain transmission on their own. Animals could, however, delay elimination using our model without animal transmission we predicted that 68 regions are expected to achieve elimination by 2030, whereas this reduces to 61 with animals. If vector control to reduce fly populations (which transmit the disease to and from hosts) are controlled in addition to medical interventions, then 147 regions are predicted to reach elimination by 2030 even with animal transmission.
Publisher: American Chemical Society (ACS)
Date: 06-07-2015
Publisher: Public Library of Science (PLoS)
Date: 29-01-2021
DOI: 10.1371/JOURNAL.PCBI.1008532
Abstract: Gambiense human African trypanosomiasis (gHAT) is a virulent disease declining in burden but still endemic in West and Central Africa. Although it is targeted for elimination of transmission by 2030, there remain numerous questions about the drivers of infection and how these vary geographically. In this study we focus on the Democratic Republic of Congo (DRC), which accounted for 84% of the global case burden in 2016, to explore changes in transmission across the country and elucidate factors which may have contributed to the persistence of disease or success of interventions in different regions. We present a Bayesian fitting methodology, applied to 168 endemic health zones (∼100,000 population size), which allows for calibration of a mechanistic gHAT model to case data (from the World Health Organization HAT Atlas) in an adaptive and automated framework. It was found that the model needed to capture improvements in passive detection to match observed trends in the data within former Bandundu and Bas Congo provinces indicating these regions have substantially reduced time to detection. Health zones in these provinces generally had longer burn-in periods during fitting due to additional model parameters. Posterior probability distributions were found for a range of fitted parameters in each health zone these included the basic reproduction number estimates for pre-1998 ( R 0 ) which was inferred to be between 1 and 1.14, in line with previous gHAT estimates, with higher median values typically in health zones with more case reporting in the 2000s. Previously, it was not clear whether a fall in active case finding in the period contributed to the declining case numbers. The modelling here accounts for variable screening and suggests that underlying transmission has also reduced greatly—on average 96% in former Equateur, 93% in former Bas Congo and 89% in former Bandundu—Equateur and Bandundu having had the highest case burdens in 2000. This analysis also sets out a framework to enable future predictions for the country.
Publisher: Springer Science and Business Media LLC
Date: 18-03-2022
DOI: 10.1038/S41467-022-29192-W
Abstract: Gambiense human African trypanosomiasis (sleeping sickness, gHAT) is a disease targeted for elimination of transmission by 2030. While annual new cases are at a historical minimum, the likelihood of achieving the target is unknown. We utilised modelling to study the impacts of four strategies using currently available interventions, including active and passive screening and vector control, on disease burden and transmission across 168 endemic health zones in the Democratic Republic of the Congo. Median projected years of elimination of transmission show only 98 health zones are on track despite significant reduction in disease burden under medical-only strategies (64 health zones if 90% certainty required). Blanket coverage with vector control is impractical, but is predicted to reach the target in all heath zones. Utilising projected disease burden under the uniform medical-only strategy, we provide a priority list of health zones for consideration for supplementary vector control alongside medical interventions.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D0AY01645D
Abstract: Bayesian modelling capturing uncertainty and correlations in circular dichroism (CD) spectra suggests it is not possible to identify more than 3 distinct secondary structure classes from CD spectra above 175 nm.
Publisher: Elsevier BV
Date: 09-2011
DOI: 10.1016/J.SSTE.2011.07.005
Abstract: At the interface of molecular biology and epidemiology, the emerging discipline of molecular epidemiology offers unique opportunities to advance the study of diseases through the investigation of infectious agents at the molecular level. Molecular tools can increase our understanding of the factors that shape the spatial and temporal distribution of pathogens and disease. Both spatial and molecular aspects have always been important to the field of infectious disease epidemiology, but recently news tools have been developed which increase our ability to consider both elements within a common framework. This enables the epidemiologist to make inferences about disease patterns in space and time. This paper introduces some basic concepts of molecular epidemiology in a veterinary context and illustrates the application of molecular tools at a range of spatio-temporal scales. Case studies - a multi-state outbreak of Serratia mastitis, a national control program for c ylobacteriosis, and evolution of foot-and-mouth-disease viruses - are used to demonstrate the importance of considering molecular aspects in modern epidemiological studies. The discipline of molecular epidemiology is in its infancy and our contribution aims to promote awareness, understanding and uptake of molecular epidemiology in veterinary science.
Publisher: Springer Science and Business Media LLC
Date: 02-03-2014
DOI: 10.1007/S11064-014-1261-Y
Abstract: Benzo[a]pyrene (BaP) is an environmental contaminant produced during incomplete combustion of organic material that is well known as a mutagenic and carcinogenic toxin. There are few studies addressing the molecular and cellular basis of behavioural alterations related to BaP exposure. The aim of this study was to evaluate the effect of subchronic oral administration of BaP on behavioral and neurochemical parameters. Wistar male rats received BaP (2 mg/kg) or corn oil (control), once a day for 28 days (n = 12/group). Spontaneous locomotor activity and short- and long-term memories were evaluated. Glial fibrillary acid protein and S100B content in the hippoc us, serum and CSF were measured using ELISA and total and phosphorylated forms of mitogen activated protein kinases (MAPKs) named extracellular signal-regulated kinases 1 and 2, p38(MAPK) and c-Jun amino-terminal kinases 1 and 2, in the hippoc us, were evaluated by western blotting. BaP induced a significant increase on locomotor activity and a decrease in short-term memory. S100B content was increased significantly in cerebrospinal fluid. BaP induced a decrease on ERK2 phosphorylation in the hippoc us. Thus, BaP subchronic treatment induces an astroglial response and impairs both motor and cognitive behavior, with parallel inhibition of ERK2, a signaling enzyme involved in the hippoc al neuroplasticity. All these effects suggest that BaP neurotoxicity is a concern for environmental pollution.
Publisher: Research Square Platform LLC
Date: 17-03-2023
DOI: 10.21203/RS.3.RS-2696883/V1
Abstract: HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15-24 years, but as new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance and longitudinal deep- sequence viral phylogenetics to assess how HIV incidence and the population groups driving transmission have evolved over a 15-year period from 2003 to 2018 in Uganda. HIV viral suppression increased more rapidly in women than men, resulting in 1.5-2 fold higher suppression rates in women with HIV by 2018 across age groups. Incidence declined more slowly in women than men, increasing pre-existing gender imbalance in HIV burden. Age-specific transmission flows shifted the share of transmission to girls and women aged 15-24 years from older men declined by approximately one third, whereas the contribution of transmission to women aged 25-34 years from men aged 0-6 years older doubled from 2003 to 2018. We estimated closing the gender gap in viral sup- pression could have reduced HIV incidence in women by half in 2018 and ended gender disparities in incidence. This study suggests that male-targeted HIV pro- grams to increase HIV suppression are critical to reduce incidence in women, close gender gaps in infection burden and improve men’s health in Africa.
Publisher: The Royal Society
Date: 18-01-2023
Abstract: Helminth transmission and morbidity are dependent on the number of mature parasites within a host however, observing adult worms is impossible for many natural infections. An outstanding challenge is therefore relating routine diagnostics, such as faecal egg counts, to the underlying worm burden. This relationship is complicated by density-dependent fecundity (egg output per worm reduces due to crowding at high burdens) and the skewed distribution of parasites (majority of helminths aggregated in a small fraction of hosts). We address these questions for the carcinogenic liver fluke Opisthorchis viverrini , which infects approximately 10 million people across Southeast Asia, by analysing five epidemiological surveys ( n = 641) where adult flukes were recovered. Using a mechanistic model, we show that parasite fecundity varies between populations, with surveys from Thailand and Laos demonstrating distinct patterns of egg output and density-dependence. As the probability of observing faecal eggs increases with the number of mature parasites within a host, we quantify diagnostic sensitivity as a function of the worm burden and find that greater than 50% of cases are misdiagnosed as false negative in communities close to elimination. Finally, we demonstrate that the relationship between observed prevalence from routine diagnostics and true prevalence is nonlinear and strongly influenced by parasite aggregation.
Publisher: Elsevier BV
Date: 03-2020
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 05-2023
End Date: 05-2026
Amount: $390,000.00
Funder: Australian Research Council
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