Lymphatic filariasis and onchocerciasis are neglected tropical diseases (NTDs) targeted for elimination by mass (antifilarial) drug administration. These drugs are predominantly active against the ...microfilarial progeny of adult worms. New drugs or combinations are needed to improve patient therapy and to enhance the effectiveness of interventions in persistent hotspots of transmission. Several therapies and regimens are currently in (pre-)clinical testing. Clinical trial simulators (CTSs) project patient outcomes to inform the design of clinical trials but have not been widely applied to NTDs, where their resource-saving payoffs could be highly beneficial. We demonstrate the utility of CTSs using our individual-based onchocerciasis transmission model (EPIONCHO-IBM) that projects trial outcomes of a hypothetical macrofilaricidal drug. We identify key design decisions that influence the power of clinical trials, including participant eligibility criteria and post-treatment follow-up times for measuring infection indicators. We discuss how CTSs help to inform target product profiles.
Objectives
Neurocysticercosis (NCC) and human immunodeficiency virus (HIV) have a high disease burden and are prevalent in overlapping low‐ and middle‐income areas. Yet, treatment guidance for people ...living with HIV/AIDS (PLWH/A) co‐infected with NCC is currently lacking. This study aims to scope the available literature on HIV/AIDS and NCC co‐infection, focusing on epidemiology, clinical characteristics, diagnostics and treatment outcomes.
Methods
The scoping literature review methodological framework, and the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines were followed. A total of 16,969 records identified through database searching, and 45 additional records from other sources were reduced to 52 included studies after a standardised selection process.
Results
Two experimental studies, ten observational studies, 23 case series/case reports and 17 reviews or letters were identified. Observational studies demonstrated similar NCC seroprevalence in PLWH/A and their HIV‐negative counterparts. Of 29 PLWH/A and NCC co‐infection, 17 (59%) suffered from epileptic seizures, 15 (52%) from headaches and 15 (52%) had focal neurological deficits. Eighteen (62%) had viable vesicular cysts, and six (21%) had calcified cysts. Fifteen (52%) were treated with albendazole, of which 11 (73%) responded well to treatment. Five individuals potentially demonstrated an immune‐reconstitution inflammatory syndrome after commencing antiretroviral therapy, although this was in the absence of immunological and neuroimaging confirmation.
Conclusions
There is a paucity of evidence to guide treatment of PLWH/A and NCC co‐infection. There is a pressing need for high‐quality studies in this patient group to appropriately inform diagnostic and management guidelines for HIV‐positive patients with NCC.
Variation in the strength of selection pressures acting upon different subpopulations may cause density-dependent regulatory processes to act differentially on particular genotypes and may influence ...the rate of selection of adaptive traits. Using host-helminth parasite systems as examples, we investigate the impact of different positive and negative density dependence on the potential spread of anthelmintic resistance. Following chemotherapy, the negative density-dependent processes restricting parasite population growth will be relaxed, increasing the genetic contribution of resistant parasites to the next generation. Simple deterministic models of directly transmitted nematodes that merge population dynamics and genetics show that the frequency of drug-resistant alleles may increase faster in species whose population size is down-regulated by density-dependent parasite fecundity than in species with density-dependent establishment or parasite mortality. A genetically structured population dynamics model of an indirectly transmitted nematode is used to highlight how population regulation will influence the resistance allele frequency in different parasite lifestages. Results indicate that surveys aimed at monitoring the evolution of drug resistance should consider carefully which life stage to sample, and the time following treatment samples should be collected. Anthelmintic resistance offers a good opportunity to apply fundamental evolutionary and ecological principles to the management of a potentially crucial public health problem.
Twenty neglected tropical diseases (NTDs) are currently prioritised by the World Health Organization for eradication, elimination as a public health problem, elimination of transmission or control by ...2030. This issue celebrates progress made since the 2012 London Declaration on NTDs and discusses challenges currently faced to achieve these goals. It comprises 14 contributions spanning NTDs tackled by intensified disease management to those addressed by preventive chemotherapy. Although COVID-19 negatively affected NTD programmes, it also served to spur new multisectoral approaches to strengthen school-based health systems. The issue highlights the needs to improve impact survey design, evaluate new diagnostics, understand the consequences of heterogeneous prevalence and human movement, the potential impact of alternative treatment strategies and the importance of zoonotic transmission. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.
...intervention programmes targeting elimination of onchocerciasis as a public health problem do not take into account OAE. ...OAE may increase onchocerciasis-related mortality among children and ...adolescents. ...NS incidence in Uganda has been brought down to zero 4. The household clustering of PWE has led communities and local healthcare workers to wrongly believe that epilepsy is contagious and transmissible by direct contact, hence increasing stigma. ...educating communities and health professionals about OAE will reduce stigma and motivate people to take ivermectin 23.
Density dependence in helminth establishment and heterogeneity in exposure to infection are known to drive resilience to interventions based on mass drug administration (MDA). However, the ...interaction between these processes is poorly understood. We developed a novel individual-based model for onchocerciasis transmission, EPIONCHO-IBM, which accounts for both processes. We fit the model to pre-intervention epidemiological data and explore parasite dynamics during MDA with ivermectin.
Density dependence and heterogeneity in exposure to blackfly (vector) bites were estimated by fitting the model to matched pre-intervention microfilarial prevalence, microfilarial intensity and vector biting rate data from savannah areas of Cameroon and Côte d'Ivoire/Burkina Faso using Latin hypercube sampling. Transmission dynamics during 25 years of annual and biannual ivermectin MDA were investigated. Density dependence in parasite establishment within humans was estimated for different levels of (fixed) exposure heterogeneity to understand how parametric uncertainty may influence treatment dynamics. Stronger overdispersion in exposure to blackfly bites results in the estimation of stronger density-dependent parasite establishment within humans, consequently increasing resilience to MDA. For all levels of exposure heterogeneity tested, the model predicts a departure from the functional forms for density dependence assumed in the deterministic version of the model.
This is the first, stochastic model of onchocerciasis, that accounts for and estimates density-dependent parasite establishment in humans alongside exposure heterogeneity. Capturing the interaction between these processes is fundamental to our understanding of resilience to MDA interventions. Given that uncertainty in these processes results in very different treatment dynamics, collecting data on exposure heterogeneity would be essential for improving model predictions during MDA. We discuss possible ways in which such data may be collected as well as the importance of better understanding the effects of immunological responses on establishing parasites prior to and during ivermectin treatment.
Age-stratified serosurvey data are often used to understand spatiotemporal trends in disease incidence and exposure through estimating the Force-of-Infection (FoI). Typically, median or mean FoI ...estimates are used as the response variable in predictive models, often overlooking the uncertainty in estimated FoI values when fitting models and evaluating their predictive ability. To assess how this uncertainty impact predictions, we compared three approaches with three levels of uncertainty integration. We propose a performance indicator to assess how predictions reflect initial uncertainty.In Colombia, 76 serosurveys (1980-2014) conducted at municipality level provided age-stratified Chagas disease prevalence data. The yearly FoI was estimated at the serosurvey level using a time-varying catalytic model. Environmental, demographic and entomological predictors were used to fit and predict the FoI at municipality level from 1980 to 2010 across Colombia.A stratified bootstrap method was used to fit the models without temporal autocorrelation at the serosurvey level. The predictive ability of each model was evaluated to select the best-fit models within urban, rural and (Amerindian) indigenous settings. Model averaging, with the 10 best-fit models identified, was used to generate predictions.Our analysis shows a risk of overconfidence in model predictions when median estimates of FoI alone are used to fit and evaluate models, failing to account for uncertainty in FoI estimates. Our proposed methodology fully propagates uncertainty in the estimated FoI onto the generated predictions, providing realistic assessments of both central tendency and current uncertainty surrounding exposure to Chagas disease.
Background Cystic echinococcosis (CE) is a zoonotic neglected tropical disease (zNTD) which imposes considerable financial burden to endemic countries. The 2021-2030 World Health Organization's ...roadmap on NTDs has proposed that intensified control be achieved in hyperendemic areas of 17 countries by 2030. Successful interventions for disease control, and the scale-up of programmes applying such interventions, rely on understanding the associated costs and relative return for investment. We conducted a scoping review of existing peer-reviewed literature on economic evaluations of CE control strategies focused on Echinococcus granulosus zoonotic hosts. Methodology/Principal findings Database searches of Scopus, PubMed, Web of Science, CABI Direct and JSTOR were conducted and comprehensively reviewed in March 2022, using predefined search criteria with no date, field or language restrictions. A total of 100 papers were initially identified and assessed for eligibility against strict inclusion and exclusion criteria, following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Bibliography review of included manuscripts was used to identify additional literature. Full review of the final manuscript selection (n = 9) was performed and cost data for control interventions were extracted. Conclusions/Significance There are very little published data pertaining to the cost and cost effectiveness of CE control interventions targeting its zoonotic hosts. Data given for costs are often incomplete, thus we were unable to perform an economic analysis and cost effectiveness study, highlighting a pressing need for this information. There is much scope for future work in this area. More detailed information and disaggregated costings need to be collected and made available. This would increase the accuracy of any cost-effective analyses to be performed and allow for a greater understanding of the opportunity cost of healthcare decisions and resource allocation by stakeholders and policy makers for effective and cost-effective CE control.
Knowledge of pattern and process in helminth population biology is mostly based on the endemic equilibrium state that characterises infections before control. Current large-scale intervention ...programmes aim at controlling/eliminating helminth infection, transmission and morbidity. As a result, age-infection profiles will be modified; immune responses will be affected; underlying parasite distributions may become more aggregated; density-dependent regulatory processes will relax; and the contribution to transmission and morbidity of different host population groups will shift. There is an urgent need to understand how the paradigm that has guided parasite population biology research is changing under chemotherapy-based control programmes for this research to continue supporting parasite control efforts effectively.
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