NOVEL DELIVERY APPROACHES OF CO-TRIMOXAZOLE FOR RECREATING ITS POTENTIAL USE-A REVIEW

Co-trimoxazole appropriates to category of broad-spectrum antimicrobial. They are active upon administration in vitro against an extensive collection of microorganisms. Their application in medical field has roughly spanned over decade now. There are numerous approaches that were progressed for improving their effectiveness towards their antimicrobial potency. However, routine use of this could accelerate the chance of bacterial resistance, and portrait it ineffective when required to treat infection. Consequently, newer investigations are necessary to keep the drug effective by minimise the development of resistance and maximise its safe use. Safe use is meant by safe delivery of drug in low dose, low frequency at the targeted molecule by effective ways. This can be achieved by using nanocarrier systems as they possess smart characteristics of effective drug delivery. These nanocarrier systems are including nanoparticle, liposomes, nanogels etc. Present review article deals with the historical perspectives with regards to co-trimoxazole, their mechanism of act/resistance and spectrum of activity in first section. In second portion different novel carriers, importance and application of nanogels, rational for co-trimoxazole nanogels are discussed. In conclusion, different literatures have proved the efficacy of nanogels in delivery of antimicrobial drug similar to co-trimoxazole. In the present time very less data is available for delivery of this drug with novel carriers. Therefore, this review aims to encourage researchers for creating some new findings in this perspective

Elimination or resurgence : modelling lymphatic filariasis after reaching the 1% microfilaremia prevalence threshold

The low prevalence levels associated with lymphatic filariasis elimination pose a challenge for effective disease surveillance. As more countries achieve the World Health Organization criteria for halting mass treatment and move on to surveillance, there is increasing reliance on the utility of transmission assessment surveys (TAS) to measure success. However, the long-term disease outcomes after passing TAS are largely untested. Using 3 well-established mathematical models, we show that low-level prevalence can be maintained for a long period after halting mass treatment and that true elimination (0% prevalence) is usually slow to achieve. The risk of resurgence after achieving current targets is low and is hard to predict using just current prevalence. Although resurgence is often quick (<5 years), it can still occur outside of the currently recommended postintervention surveillance period of 4–6 years. Our results highlight the need for ongoing and enhanced postintervention monitoring, beyond the scope of TAS, to ensure sustained success

Comparing antigenaemia- and microfilaraemia as criteria for stopping decisions in lymphatic filariasis elimination programmes in Africa

BACKGROUND: Mass drug administration (MDA) is the main strategy towards lymphatic filariasis (LF) elimination. Progress is monitored by assessing microfilaraemia (Mf) or circulating filarial antigenaemia (CFA) prevalence, the latter being more practical for field surveys. The current criterion for stopping MDA requires \u3c2% CFA prevalence in 6- to 7-year olds, but this criterion is not evidence-based. We used mathematical modelling to investigate the validity of different thresholds regarding testing method and age group for African MDA programmes using ivermectin plus albendazole. METHODOLGY/PRINCIPAL FINDINGS: We verified that our model captures observed patterns in Mf and CFA prevalence during annual MDA, assuming that CFA tests are positive if at least one adult worm is present. We then assessed how well elimination can be predicted from CFA prevalence in 6-7-year-old children or from Mf or CFA prevalence in the 5+ or 15+ population, and determined safe (\u3e95% positive predictive value) thresholds for stopping MDA. The model captured trends in Mf and CFA prevalences reasonably well. Elimination cannot be predicted with sufficient certainty from CFA prevalence in 6-7-year olds. Resurgence may still occur if all children are antigen-negative, irrespective of the number tested. Mf-based criteria also show unfavourable results (PPV \u3c95% or unpractically low threshold). CFA prevalences in the 5+ or 15+ population are the best predictors, and post-MDA threshold values for stopping MDA can be as high as 10% for 15+. These thresholds are robust for various alternative assumptions regarding baseline endemicity, biological parameters and sampling strategies. CONCLUSIONS/SIGNIFICANCE: For African areas with moderate to high pre-treatment Mf prevalence that have had 6 or more rounds of annual ivermectin/albendazole MDA with adequate coverage, we recommend to adopt a CFA threshold prevalence of 10% in adults (15+) for stopping MDA. This could be combined with Mf testing of CFA positives to ensure absence of a significant Mf reservoir for transmission

An Ensemble Framework for Projecting the Impact of Lymphatic Filariasis Interventions Across Sub-Saharan Africa at a Fine Spatial Scale

Background: Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as a public health problem by 2030. Although mass treatments have led to huge reductions in LF prevalence, some countries or regions may find it difficult to achieve elimination by 2030 owing to various factors, including local differences in transmission. Subnational projections of intervention impact are a useful tool in understanding these dynamics, but correctly characterizing their uncertainty is challenging. Methods: We developed a computationally feasible framework for providing subnational projections for LF across 44 sub-Saharan African countries using ensemble models, guided by historical control data, to allow assessment of the role of subnational heterogeneities in global goal achievement. Projected scenarios include ongoing annual treatment from 2018 to 2030, enhanced coverage, and biannual treatment. Results: Our projections suggest that progress is likely to continue well. However, highly endemic locations currently deploying strategies with the lower World Health Organization recommended coverage (65%) and frequency (annual) are expected to have slow decreases in prevalence. Increasing intervention frequency or coverage can accelerate progress by up to 5 or 6 years, respectively. Conclusions: While projections based on baseline data have limitations, our methodological advancements provide assessments of potential bottlenecks for the global goals for LF arising from subnational heterogeneities. In particular, areas with high baseline prevalence may face challenges in achieving the 2030 goals, extending the "tail"of interventions. Enhancing intervention frequency and/or coverage will accelerate progress. Our approach facilitates preimplementation assessments of the impact of local interventions and is applicable to other regions and neglected tropical diseases.</p

Quantifying the value of surveillance data for improving model predictions of lymphatic filariasis elimination

BACKGROUND: Mathematical models are increasingly being used to evaluate strategies aiming to achieve the control or elimination of parasitic diseases. Recently, owing to growing realization that process-oriented models are useful for ecological forecasts only if the biological processes are well defined, attention has focused on data assimilation as a means to improve the predictive performance of these models.METHODOLOGY AND PRINCIPAL FINDINGS: We report on the development of an analytical framework to quantify the relative values of various longitudinal infection surveillance data collected in field sites undergoing mass drug administrations (MDAs) for calibrating three lymphatic filariasis (LF) models (EPIFIL, LYMFASIM, and TRANSFIL), and for improving their predictions of the required durations of drug interventions to achieve parasite elimination in endemic populations. The relative information contribution of site-specific data collected at the time points proposed by the WHO monitoring framework was evaluated using model-data updating procedures, and via calculations of the Shannon information index and weighted variances from the probability distributions of the estimated timelines to parasite extinction made by each model. Results show that data-informed models provided more precise forecasts of elimination timelines in each site compared to model-only simulations. Data streams that included year 5 post-MDA microfilariae (mf) survey data, however, reduced each model's uncertainty most compared to data streams containing only baseline and/or post-MDA 3 or longer-term mf survey data irrespective of MDA coverage, suggesting that data up to this monitoring point may be optimal for informing the present LF models. We show that the improvements observed in the predictive performance of the best data-informed models may be a function of temporal changes in inter-parameter interactions. Such best data-informed models may also produce more accurate predictions of the duratio

Delays in lymphatic filariasis elimination programmes due to COVID-19, and possible mitigation strategies

Background In view of the current global coronavirus disease 2019 pandemic, mass drug administration interventions for neglected tropical diseases, including lymphatic filariasis (LF), have been halted. We used mathematical modelling to estimate the impact of delaying or cancelling treatment rounds and explore possible mitigation strategies. Methods We used three established LF transmission models to simulate infection trends in settings with annual treatment rounds and programme delays in 2020 of 6, 12, 18 or 24 months. We then evaluated the impact of various mitigation strategies upon resuming activities. Results The delay in achieving the elimination goals is on average similar to the number of years the treatment rounds are missed. Enhanced interventions implemented for as little as 1 y can allow catch-up on the progress lost and, if maintained throughout the programme, can lead to acceleration of up to 3 y. Conclusions In general, a short delay in the programme does not cause a major delay in achieving the goals. Impact is strongest in high-endemicity areas. Mitigation strategies such as biannual treatment or increased coverage are key to minimizing the impact of the disruption once the programme resumes and lead to potential acceleration should these enhanced strategies be maintained

An Ensemble Framework for Projecting the Impact of Lymphatic Filariasis Interventions Across Sub-Saharan Africa at a Fine Spatial Scale

BackgroundLymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as a public health problem by 2030. Although mass treatments have led to huge reductions in LF prevalence, some countries or regions may find it difficult to achieve elimination by 2030 owing to various factors, including local differences in transmission. Subnational projections of intervention impact are a useful tool in understanding these dynamics, but correctly characterizing their uncertainty is challenging.MethodsWe developed a computationally feasible framework for providing subnational projections for LF across 44 sub-Saharan African countries using ensemble models, guided by historical control data, to allow assessment of the role of subnational heterogeneities in global goal achievement. Projected scenarios include ongoing annual treatment from 2018 to 2030, enhanced coverage, and biannual treatment.ResultsOur projections suggest that progress is likely to continue well. However, highly endemic locations currently deploying strategies with the lower World Health Organization recommended coverage (65%) and frequency (annual) are expected to have slow decreases in prevalence. Increasing intervention frequency or coverage can accelerate progress by up to 5 or 6 years, respectively.ConclusionsWhile projections based on baseline data have limitations, our methodological advancements provide assessments of potential bottlenecks for the global goals for LF arising from subnational heterogeneities. In particular, areas with high baseline prevalence may face challenges in achieving the 2030 goals, extending the "tail" of interventions. Enhancing intervention frequency and/or coverage will accelerate progress. Our approach facilitates preimplementation assessments of the impact of local interventions and is applicable to other regions and neglected tropical diseases

An Ensemble Framework for Projecting the Impact of Lymphatic Filariasis Interventions Across Sub-Saharan Africa at a Fine Spatial Scale.

Background Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as a public health problem by 2030. Although mass treatments have led to huge reductions in LF prevalence, some countries or regions may find it difficult to achieve elimination by 2030 owing to various factors, including local differences in transmission. Subnational projections of intervention impact are a useful tool in understanding these dynamics, but correctly characterizing their uncertainty is challenging. Methods We developed a computationally feasible framework for providing subnational projections for LF across 44 sub-Saharan African countries using ensemble models, guided by historical control data, to allow assessment of the role of subnational heterogeneities in global goal achievement. Projected scenarios include ongoing annual treatment from 2018 to 2030, enhanced coverage, and biannual treatment. Results Our projections suggest that progress is likely to continue well. However, highly endemic locations currently deploying strategies with the lower World Health Organization recommended coverage (65%) and frequency (annual) are expected to have slow decreases in prevalence. Increasing intervention frequency or coverage can accelerate progress by up to 5 or 6 years, respectively. Conclusions While projections based on baseline data have limitations, our methodological advancements provide assessments of potential bottlenecks for the global goals for LF arising from subnational heterogeneities. In particular, areas with high baseline prevalence may face challenges in achieving the 2030 goals, extending the "tail" of interventions. Enhancing intervention frequency and/or coverage will accelerate progress. Our approach facilitates preimplementation assessments of the impact of local interventions and is applicable to other regions and neglected tropical diseases

Mathematical Analysis of a Single-Species Population Model in a Polluted Environment with Discrete Time Delays

We have discussed the dynamical behaviour of a single-species population model in a polluted environment which describes the effect of toxicants on ecological system. Boundedness, positivity, and stability analysis of the model at various equilibrium points is discussed thoroughly. We have also studied the effect of single discrete delay as well as double discrete delays on the population model. Existence conditions of the Hopf bifurcation for single time delay are investigated. The length of delay preserving the stability is also estimated. The direction and the stability criteria of the bifurcating periodic solutions are determined by using the normal form theory and the center manifold theorem. The stability of the model with double time delays is investigated by using the Nyquist criteria. By choosing one of the delays as a bifurcation parameter, the model is found to undergo a Hopf bifurcation. Some numerical simulations for justifying the theoretical results are also illustrated by using MATLAB, which shows the reliability of our model from the practical point of view

Epidemic progression and vaccination in a heterogeneous population. Application to the Covid-19 epidemic

International audienceThe paper is devoted to a compartmental epidemiological model of infection progression in a heterogeneous population which consists of two groups with high disease transmission (HT) and low disease transmission (LT) potentials. Final size and duration of epidemic, the total and current maximal number of infected individuals are estimated depending on the structure of the population. It is shown that with the same basic reproduction number R 0 in the beginning of epidemic, its further progression depends on the ratio between the two groups. Therefore, fitting the data in the beginning of epidemic and the determination of R 0 are not sufficient to predict its long time behaviour. Available data on the Covid-19 epidemic allows the estimation of the proportion of the HT and LT groups. Estimated structure of the population is used for the investigation of the influence of vaccination on further epidemic development. The result of vaccination strongly depends on the proportion of vaccinated individuals between the two groups. Vaccination of the HT group acts to stop the epidemic and essentially decreases the total number of infected individuals at the end of epidemic and the current maximal number of infected individuals while vaccination of the LT group only acts to protect vaccinated individuals from further infection