Modelling timelines to elimination of sleeping sickness in the Democratic Republic of Congo, accounting for possible cryptic human and animal transmission.

Background: Sleeping sickness (gambiense human African trypanosomiasis, gHAT) is a vector-borne disease targeted for global elimination of transmission (EoT) by 2030. There are, however, unknowns that have the potential to hinder the achievement and measurement of this goal. These include asymptomatic gHAT infections (inclusive of the potential to self-cure or harbour skin-only infections) and whether gHAT infection in animals can contribute to the transmission cycle in humans.

Modelling to explore the potential impact of asymptomatic human infections on transmission and dynamics of African sleeping sickness.

Gambiense human African trypanosomiasis (gHAT, sleeping sickness) is one of several neglected tropical diseases (NTDs) where there is evidence of asymptomatic human infection but there is uncertainty of the role it plays in transmission and maintenance. To explore possible consequences of asymptomatic infections, particularly in the context of elimination of transmission-a goal set to be achieved by 2030-we propose a novel dynamic transmission model to account for the asymptomatic population. This extends an established framework, basing infection progression on a number of experimental and observation gHAT studies.

Modelling to Quantify the Likelihood that Local Elimination of Transmission has Occurred Using Routine Gambiense Human African Trypanosomiasis Surveillance Data.

Background: The gambiense human African trypanosomiasis (gHAT) elimination programme in the Democratic Republic of Congo (DRC) routinely collects case data through passive surveillance and active screening, with several regions reporting no cases for several years, despite being endemic in the early 2000s.

Methods: We use mathematical models fitted to longitudinal data to estimate the probability that selected administrative regions have already achieved elimination of transmission (EOT) of gHAT. We examine the impact of active screening coverage on the certainty of model estimates for transmission and therefore the role of screening in the measurement of EOT.

Predicting the impact of COVID-19 interruptions on transmission of gambiense human African trypanosomiasis in two health zones of the Democratic Republic of Congo.

Many control programmes against neglected tropical diseases have been interrupted due to the coronavirus disease 2019 (COVID-19) pandemic, including those that rely on active case finding. In this study we focus on gambiense human African trypanosomiasis (gHAT), where active screening was suspended in the Democratic Republic of Congo (DRC) due to the pandemic. We use two independent mathematical models to predict the impact of COVID-19 interruptions on transmission and reporting and achievement of the 2030 elimination of transmission (EOT) goal for gHAT in two moderate-risk regions of the DRC.

Estimating the distribution of time to extinction of infectious diseases in mean-field approaches.

A key challenge for many infectious diseases is to predict the time to extinction under specific interventions. In general, this question requires the use of stochastic models which recognize the inherent individual-based, chance-driven nature of the dynamics; yet stochastic models are inherently computationally expensive, especially when parameter uncertainty also needs to be incorporated. Deterministic models are often used for prediction as they are more tractable; however, their inability to precisely reach zero infections makes forecasting extinction times problematic.

Predicted Impact of COVID-19 on Neglected Tropical Disease Programs and the Opportunity for Innovation.

Due to the COVID-19 pandemic, many key neglected tropical disease (NTD) activities have been postponed. This hindrance comes at a time when the NTDs are progressing towards their ambitious goals for 2030. Mathematical modelling on several NTDs, namely gambiense sleeping sickness, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiases (STH), trachoma, and visceral leishmaniasis, shows that the impact of this disruption will vary across the diseases.

Screening Strategies for a Sustainable Endpoint for Gambiense Sleeping Sickness.

Background: Gambiense human African trypanosomiasis ([gHAT] sleeping sickness) is a vector-borne disease that is typically fatal without treatment. Intensified, mainly medical-based, interventions in endemic areas have reduced the occurrence of gHAT to historically low levels. However, persistent regions, primarily in the Democratic Republic of Congo (DRC), remain a challenge to achieving the World Health Organization's goal of global elimination of transmission (EOT).

Patterns of Polar Domains in a Spatiotemporal Model of Interacting Polarities.

Polarity fields are known to exhibit long distance patterns, in both physical and biological systems. The mechanisms behind such patterns are poorly understood. Here, we describe the dynamics of polarity fields using an original physical model that generalizes classical spin models on a lattice by incorporating effective transport of polarity molecules between neighboring sites.

The Selector Gene apterous and Notch Are Required to Locally Increase Mechanical Cell Bond Tension at the Drosophila Dorsoventral Compartment Boundary.

The separation of cells with distinct fates and functions is important for tissue and organ formation during animal development. Regions of different fates within tissues are often separated from another along straight boundaries. These compartment boundaries play a crucial role in tissue patterning and growth by stably positioning organizers.

A local difference in Hedgehog signal transduction increases mechanical cell bond tension and biases cell intercalations along the Drosophila anteroposterior compartment boundary.

Tissue organization requires the interplay between biochemical signaling and cellular force generation. The formation of straight boundaries separating cells with different fates into compartments is important for growth and patterning during tissue development. In the developing Drosophila wing disc, maintenance of the straight anteroposterior (AP) compartment boundary involves a local increase in mechanical tension at cell bonds along the boundary.

Local increases in mechanical tension shape compartment boundaries by biasing cell intercalations.

Mechanical forces play important roles during tissue organization in developing animals. Many tissues are organized into adjacent, nonmixing groups of cells termed compartments. Boundaries between compartments display a straight morphology and are associated with signaling centers that are important for tissue growth and patterning.

Physical mechanisms shaping the Drosophila dorsoventral compartment boundary.

Background: Separating cells with distinct identities and fates by straight and sharp compartment boundaries is important for growth and pattern formation during animal development. The physical mechanisms shaping compartment boundaries, however, are not fully understood.

Results: We combine theory and quantitative experiments to investigate the roles of different mechanisms to shape compartment boundaries.

Mechanical properties of an adsorbed elastic polymer in contact with a rigid membrane.

A static and a dynamical model are introduced to study the physical properties of an elastic polymer adsorbed on a rigid membrane. We analyze the detailed microscopic model for the adhesion problem and show that in the force ensemble a critical force is expected. Forces smaller than the critical value are not able to peel off the filament, while larger forces will cause the filament to completely desorb from the membrane.