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Modelling the Impact of Vector Control on Lymphatic Filariasis Programs: Current Approaches and Limitations.

ABSTRACT: Vector control is widely considered an important tool for lymphatic filariasis (LF) elimination but is not usually included in program budgets and has often been secondary to other policy questions in modelling studies. Evidence from the field demonstrates that vector control can have a large impact on program outcomes and even halt transmission entirely, but implementation is expensive. Models of LF have the potential to inform where and when resources should be focused, but often simplify vector dynamics and focus on capturing human prevalence trends, making them comparatively ill-designed for direct analysis of vector control measures. We review the recent modelling literature and present additional results using a well-established model, highlighting areas of agreement between model predictions and field evidence, and discussing the possible determinants of existing disagreements. We conclude that there are likely to be long-term benefits of vector control, both on accelerating programs and preventing resurgence.

SUBMITTER: Davis EL

PROVIDER: S-EPMC8201547 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Modelling the Impact of Vector Control on Lymphatic Filariasis Programs: Current Approaches and Limitations.

Davis E L EL Prada J J Reimer L J LJ Hollingsworth T D TD

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20210601 Suppl 3

Vector control is widely considered an important tool for lymphatic filariasis (LF) elimination but is not usually included in program budgets and has often been secondary to other policy questions in modelling studies. Evidence from the field demonstrates that vector control can have a large impact on program outcomes and even halt transmission entirely, but implementation is expensive. Models of LF have the potential to inform where and when resources should be focused, but often simplify vect ...[more]

PMID: 33905475

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Project description:BackgroundThe current global efforts to control the morbidity and mortality caused by infectious diseases affecting developing countries--such as HIV/AIDS, polio, tuberculosis, malaria and the Neglected Tropical Diseases (NTDs)-have led to an increasing focus on the biological controllability or eradicability of disease transmission by management action. Here, we use an age-structured dynamical model of lymphatic filariasis transmission to show how a quantitative understanding of the dynamic processes underlying infection persistence and extinction is key to evaluating the eradicability of this macroparasitic disease.Methodology/principal findingsWe investigated the persistence and extinction dynamics of lymphatic filariasis by undertaking a numerical equilibrium analysis of a deterministic model of parasite transmission, based on varying values of the initial L3 larval density in the system. The results highlighted the likely occurrence of complex dynamics in parasite transmission with three major outcomes for the eradicability of filariasis. First, both vector biting and worm breakpoint thresholds are shown to be complex dynamic entities with values dependent on the nature and magnitude of vector-and host specific density-dependent processes and the degree of host infection aggregation prevailing in endemic communities. Second, these thresholds as well as the potential size of the attractor domains and hence system resilience are strongly dependent on peculiarities of infection dynamics in different vector species. Finally, the existence of multiple stable states indicates the presence of hysteresis nonlinearity in the filariasis system dynamics in which infection thresholds for infection invasion are lower but occur at higher biting rates than do the corresponding thresholds for parasite elimination.Conclusions/significanceThe variable dynamic nature of thresholds and parasite system resilience reflecting both initial conditions and vector species-infection specificities, and the existence of hysteresis loop phenomenon, suggests that eradication of filariasis may require taking a more flexible and locally relevant approach to designing elimination programmes compared to the current command and control approach advocated by the global programme.

Project description:Photodynamic therapy (PDT) mostly relies on the generation of singlet oxygen, via the excitation of a photosensitizer, so that target tumor cells can be destroyed. PDT can be applied in the settings of several malignant diseases. In fact, the earliest preclinical applications date back to 1900's. Dougherty reported the treatment of skin tumors by PDT in 1978. Several further studies around 1980 demonstrated the effectiveness of PDT. Thus, the technique has attracted the attention of numerous researchers since then. Hematoporphyrin derivative received the FDA approval as a clinical application of PDT in 1995. We have indeed witnessed a considerable progress in the field over the last century. Given the fact that PDT has a favorable adverse event profile and can enhance anti-tumor immune responses as well as demonstrating minimally invasive characteristics, it is disappointing that PDT is not broadly utilized in the clinical setting for the treatment of malignant and/or non-malignant diseases. Several issues still hinder the development of PDT, such as those related with light, tissue oxygenation and inherent properties of the photosensitizers. Various photosensitizers have been designed/synthesized in order to overcome the limitations. In this Review, we provide a general overview of the mechanisms of action in terms of PDT in cancer, including the effects on immune system and vasculature as well as mechanisms related with tumor cell destruction. We will also briefly mention the application of PDT for non-malignant diseases. The current limitations of PDT utilization in cancer will be reviewed, since identifying problems associated with design/synthesis of photosensitizers as well as application of light and tissue oxygenation might pave the way for more effective PDT approaches. Furthermore, novel promising approaches to improve outcome in PDT such as selectivity, bioengineering, subcellular/organelle targeting, etc. will also be discussed in detail, since the potential of pioneering and exceptional approaches that aim to overcome the limitations and reveal the full potential of PDT in terms of clinical translation are undoubtedly exciting. A better understanding of novel concepts in the field (e.g. enhanced, two-stage, fractional PDT) will most likely prove to be very useful for pursuing and improving effective PDT strategies.

Dataset Information

Modelling the Impact of Vector Control on Lymphatic Filariasis Programs: Current Approaches and Limitations.

Publications

Modelling the Impact of Vector Control on Lymphatic Filariasis Programs: Current Approaches and Limitations.

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