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Gambiense human African trypanosomiasis is a deadly disease that has been declining in incidence since the start of the Century, primarily due to increased screening, diagnosis and treatment of infected people. The main treatment regimen currently in use requires a lumbar puncture as part of the diagnostic process to determine disease stage and hos...
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... adapted the stochastic formulation of the population-based gHAT transmission and control model described in [16], which builds on previous work [13,17]. A schematic of the model is shown in Fig 1, and a description of the corresponding state variables is given in Table 1. The model is based on a system of ordinary differential equations that include tsetse flies, humans in multiple disease stages, and two risk settings. ...Citations
... 86 , 87 The development of fexinidazole as an oral treatment for both the stages of HAT is an important development 88 ; effective treatment compliance might be the key. 89 The number of HAT cases is generally low and the burden appears to be mostly in the coastal region. Targeted active surveillance will lead to early identification of patients in stage 1, as passively diagnosed patients are more likely to present with later stages of the disease. ...
Neglected tropical diseases (NTDs) predominantly affect vulnerable and marginalized populations in tropical and subtropical areas and globally affect more than one billion people. In Guinea, the burden of NTDs is estimated to be >7.5 disability-adjusted life years per million inhabitants. Currently the Guinea NTDs master plan (2017-2020) has identified eight diseases as public health problems: onchocerciasis, lymphatic filariasis, trachoma, schistosomiasis and soil-transmitted helminthiasis, leprosy, human African trypanosomiasis and Buruli ulcer. In this review we discuss the past and the current case burden of the priority NTDs in Guinea, highlight the major milestones and discuss current and future areas of focus for achieving the 2030 target outlined by the World Health Organization.
... Nord and Sud coordinations. In each health zone, the baseline strategy is either MeanAS or MeanAS+VC depending on its VC status (summarised in Table 1 the potential pros and cons from a transmission perspective of fexinidazole [39]. They found that reductions in compliance in treatment could lead to lower effectiveness, but there were also the possibility for improved access to treatment and subsequently reduced transmission. ...
Gambiense human African trypanosomiasis (gHAT) is a deadly vector-borne, neglected tropical disease found in West and Central Africa targeted for elimination of transmission (EoT) by 2030. The recent pandemic has illustrated how it can be important to quantify the impact that unplanned disruption to programme activities may have in achieving EoT. We used a previously developed model of gHAT fitted to data from the Democratic Republic of the Congo, the country with the highest global case burden, to explore how interruptions to intervention activities, due to e.g. COVID-19, Ebola or political instability, could impact progress towards EoT and gHAT burden. We simulated transmission and reporting dynamics in 38 regions within Kwilu, Mai Ndombe and Kwango provinces under six interruption scenarios lasting for nine or twenty-one months. Included in the interruption scenarios are the cessation of active screening in all scenarios and a reduction in passive detection rates and a delay or suspension of vector control deployments in some scenarios. Our results indicate that, even under the most extreme 21-month interruption scenario, EoT is not predicted to be delayed by more than one additional year compared to the length of the interruption. If existing vector control deployments continue, we predict no delay in achieving EoT even when both active and passive screening activities are interrupted. If passive screening remains as functional as in 2019, we expect a marginal negative impact on transmission, however this depends on the strength of passive screening in each health zone. We predict a pronounced increase in additional gHAT disease burden (morbidity and mortality) in many health zones if both active and passive screening were interrupted compared to the interruption of active screening alone. The ability to continue existing vector control during medical activity interruption is also predicted to avert a moderate proportion of disease burden.
... Another modelling study has explored the potential pros 423 and cons from a transmission perspective of fexinidazole. They found that reductions in 424 compliance in treatment could lead to lower effectiveness but there were also the 425 possibility for improved access to treatment and subsequently reduced transmission [34]. 426 Should the oral, single-dose drug, acoziborole, become available following completion of 427 clinical trials [35] and have a suitable safety profile, it may be possible for the gHAT 428 programme to add a "screen and treat" algorithm in the coming years. ...
Gambiense human African trypanosomiasis (gHAT) is a deadly vector-borne, neglected tropical disease found in West and Central Africa targeted for elimination of transmission (EoT) by 2030. The recent pandemic has illustrated how it can be important to quantify the impact that unplanned disruption to programme activities may have in achieving elimination of transmission. We used a previously developed model of gHAT fitted to data from the Democratic Republic of Congo, a country with the highest global case burden, to explore how interruptions to intervention activities, due to e.g. COVID-19, Ebola or political instability, could impact progress towards EoT and gHAT burden. We simulated transmission and reporting dynamics in 38 health zones under six interruption scenarios lasting for nine or twenty-one months. Included in the interruption scenarios are the cessation of active screening in all scenarios and a reduction in passive detection rates and a delay or suspension of vector control deployments in some scenarios. Our results indicate that, even under the most extreme 21-month interruption scenario, EoT is not predicted to be delayed by more than one additional year compared to the length of the interruption. If existing vector control deployments continue, we predict no delay in achieving EoT even when both active and passive screening activities are interrupted. If passive screening remains fully functional, we expect a marginal negative impact on transmission, however this depends on the strength of passive screening in each health zone. We predict a pronounced increase in additional gHAT disease burden (morbidity and mortality) in many health zones if both active and passive screening were interrupted compared to the interruption of active screening alone. The ability to continue existing vector control during medical activity interruption is also predicted to avert a moderate proportion of disease burden.
Author Summary
Whilst the COVID-19 pandemic has produced wide-spread disruption for many disease programmes there are also a range of other factors that continue to risk programme interruptions including other disease outbreaks (e.g. Ebola, cholera, yellow fever, and measles) and the potential for political instability. In this study we examine the impact of interruptions by external factors to the gambiense human African trypanosomiasis (gHAT, sleeping sickness) elimination programme of the Democratic Republic of the Congo, a country which has the highest global case burden. We use our previously fitted gHAT model to simulate how transmission dynamics might be impacted by disruption to medical interventions and (where relevant) vector control activities in 38 health zones of the former Bandundu province. For each of the six interruption scenarios we use the model to forecast case numbers and disease burden as well as estimating the expected years and probabilities of elimination of transmission. This analysis provides invaluable insight into the impact that interruptions of any persuasion could have on burden, case reporting and time to achieve elimination of transmission of gHAT in the Democratic Republic of the Congo.
The drug discovery process aims to identify new chemical entities (NCEs) that are therapeutically beneficial for the management and/or cure of diseases. Such novel compounds have been identified using various strategies that include phenotypic drug discovery (PDD), target-based drug discovery (TDD) and serendipitous drug discovery (SDD). PDD is an empirical approach and has been a more successful strategy for discovering small molecule, first-in-class drugs. Phenotypic screening involves testing a molecule in cells, isolated tissues, or animals to evaluate the desired effect without exactly knowing the mechanism of action. TDD approach, on the other hand, has yielded more best in class drugs. It is a complex process that initiates the identification and validation of novel targets. To accelerate target analysis, high throughput screening (HTS) has played a pivotal role by cost-effectively screening large-scale compound libraries. The target identification is followed by synthesis, characterization, and screening of NCEs in assays relevant to the disease target to find therapeutic efficacy. Advanced techniques in molecular biology and genomics have made TDD a preferred approach to drug discovery in the pharmaceutical industry. SDD has also played an important role in the drug discovery process, particularly in the discovery of psychotropic drugs that have led to the management of several psychiatric disorders. This chapter highlights successful drug discoveries achieved so far by applying the three approaches mentioned above, citing a few examples of successful drugs for each strategy.
