scholarly journals Development of emodepside as a possible adulticidal treatment for human onchocerciasis—The fruit of a successful industrial–academic collaboration

2021 ◽  
Vol 17 (7) ◽  
pp. e1009682
Author(s):  
Jürgen Krücken ◽  
Lindy Holden-Dye ◽  
Jennifer Keiser ◽  
Roger K. Prichard ◽  
Simon Townson ◽  
...  
Keyword(s):  
Drug Development ◽  
Broad Spectrum ◽  
Neglected Tropical Diseases ◽  
Current Knowledge ◽  
Animal Health ◽  
World Health ◽  
Parasitic Nematodes ◽  
Term Therapy ◽  
Neglected Diseases ◽  
Phase I Clinical Trials

Current mass drug administration (MDA) programs for the treatment of human river blindness (onchocerciasis) caused by the filarial worm Onchocerca volvulus rely on ivermectin, an anthelmintic originally developed for animal health. These treatments are primarily directed against migrating microfilariae and also suppress fecundity for several months, but fail to eliminate adult O. volvulus. Therefore, elimination programs need time frames of decades, well exceeding the life span of adult worms. The situation is worsened by decreased ivermectin efficacy after long-term therapy. To improve treatment options against onchocerciasis, a drug development candidate should ideally kill or irreversibly sterilize adult worms. Emodepside is a broad-spectrum anthelmintic used for the treatment of parasitic nematodes in cats and dogs (Profender and Procox). Our current knowledge of the pharmacology of emodepside is the result of more than 2 decades of intensive collaborative research between academia and the pharmaceutical industry. Emodepside has a novel mode of action with a broad spectrum of activity, including against extraintestinal nematode stages such as migrating larvae or macrofilariae. Therefore, emodepside is considered to be among the most promising candidates for evaluation as an adulticide treatment against onchocerciasis. Consequently, in 2014, Bayer and the Drugs for Neglected Diseases initiative (DNDi) started a collaboration to develop emodepside for the treatment of patients suffering from the disease. Macrofilaricidal activity has been demonstrated in various models, including Onchocerca ochengi in cattle, the parasite most closely related to O. volvulus. Emodepside has now successfully passed Phase I clinical trials, and a Phase II study is planned. This Bayer–DNDi partnership is an outstanding example of “One World Health,” in which experience gained in veterinary science and drug development is translated to human health and leads to improved tools to combat neglected tropical diseases (NTDs) and shorten development pathways and timelines in an otherwise neglected area.

scholarly journals Novel transdisciplinary methodology for cross-sectional analysis of snakebite epidemiology at national scale

2021 ◽  
Vol 15 (2) ◽  
pp. e0009023
Author(s):  
Gabriel Alcoba ◽  
Carlos Ochoa ◽  
Sara Babo Martins ◽  
Rafael Ruiz de Castañeda ◽  
Isabelle Bolon ◽  
...  
Keyword(s):  
Large Scale ◽  
Survey Methodology ◽  
Neglected Tropical Diseases ◽  
Animal Health ◽  
Epidemiological Data ◽  
World Health ◽  
Primary Data ◽  
Cross Sectional ◽  
High Resolution Satellite Images ◽  
The Impact

Background Worldwide, it is estimated that snakes bite 4.5–5.4 million people annually, 2.7 million of which are envenomed, and 81,000–138,000 die. The World Health Organization reported these estimates and recognized the scarcity of large-scale, community-based, epidemiological data. In this context, we developed the “Snake-Byte” project that aims at (i) quantifying and mapping the impact of snakebite on human and animal health, and on livelihoods, (ii) developing predictive models for medical, ecological and economic indicators, and (iii) analyzing geographic accessibility to healthcare. This paper exclusively describes the methodology we developed to collect large-scale primary data on snakebite in humans and animals in two hyper-endemic countries, Cameroon and Nepal. Methodology/Principal findings We compared available methods on snakebite epidemiology and on multi-cluster survey development. Then, in line with those findings, we developed an original study methodology based on a multi-cluster random survey, enhanced by geospatial, One Health, and health economics components. Using a minimum hypothesized snakebite national incidence of 100/100,000/year and optimizing design effect, confidence level, and non-response margin, we calculated a sample of 61,000 people per country. This represented 11,700 households in Cameroon and 13,800 in Nepal. The random selection with probability proportional to size generated 250 clusters from all Cameroonian regions and all Nepalese Terai districts. Our household selection methodology combined spatial randomization and selection via high-resolution satellite images. After ethical approval in Switerland (CCER), Nepal (BPKIHS), and Cameroon (CNERSH), and informed written consent, our e-questionnaires included geolocated baseline demographic and socio-economic characteristics, snakebite clinical features and outcomes, healthcare expenditure, animal ownership, animal outcomes, snake identification, and service accessibility. Conclusions/Significance This novel transdisciplinary survey methodology was subsequently used to collect countrywide snakebite envenoming data in Nepal and Cameroon. District-level incidence data should help health authorities to channel antivenom and healthcare allocation. This methodology, or parts thereof, could be easily adapted to other countries and to other Neglected Tropical Diseases.

scholarly journals New global targets for NTDs in the WHO roadmap 2021–2030

2021 ◽  
Vol 15 (5) ◽  
pp. e0009373
Author(s):  
Adriano Casulli
Keyword(s):  
Prevention And Control ◽  
Neglected Tropical Diseases ◽  
World Health ◽  
Neglected Diseases ◽  
Tropical Diseases ◽  
Future Prospects ◽  
The World ◽  
Health Organization ◽  
And Control ◽  
Second World

The second World Neglected Tropical Diseases (NTDs) Day was celebrated on 30 January 2021. To mark the occasion, the World Health Organization (WHO) launched its roadmap for NTDs for the period 2021 to 2030, which is aimed at increasing prevention and control of these too-long neglected diseases. Described here is a global overview on past achievements, current challenges, and future prospects for the WHO NTDs roadmap 2021–2030.

scholarly journals One Health for neglected tropical diseases

2020 ◽  
Author(s):  
Gabrielle Laing ◽  
Marco Antonio Natal Vigilato ◽  
Sarah Cleaveland ◽  
S M Thumbi ◽  
Lucille Blumberg ◽  
...  
Keyword(s):  
One Health ◽  
Neglected Tropical Diseases ◽  
Animal Health ◽  
World Health ◽  
Shared Environment ◽  
Tropical Diseases ◽  
Road Map ◽  
The One ◽  
Health Organization ◽  
And Control

Abstract The forthcoming World Health Organization road map for neglected tropical diseases (NTDs) 2021–2030 recognises the complexity surrounding control and elimination of these 20 diseases of poverty. It emphasises the need for a paradigm shift from disease-specific interventions to holistic cross-cutting approaches coordinating with adjacent disciplines. The One Health approach exemplifies this shift, extending beyond a conventional model of zoonotic disease control to consider the interactions of human and animal health systems within their shared environment and the wider social and economic context. This approach can also promote sustainability and resilience within these systems. To achieve the global ambition on NTD elimination and control, political will, along with contextualised innovative scientific strategies, is required.

A Scoping Review of the Effectiveness of Control Interventions of Human and Canine Rabies in an Effort to Rationalise the One Health Approach

2020 ◽  
Vol 1 (1) ◽  
pp. 16-34
Author(s):  
Nur Asheila Abdul Taib ◽  
Razitasham Safii
Keyword(s):  
World Health Organization ◽  
Scoping Review ◽  
One Health ◽  
Neglected Tropical Diseases ◽  
Animal Health ◽  
World Health ◽  
Human Rabies ◽  
Canine Rabies ◽  
The One ◽  
Health Organization

  According to the World Health Organization (WHO), rabies is one of the 18 neglected tropical diseases, together with dengue, leprosy, and trachoma, among others. Despite being a vaccine-preventable disease, the latest estimate of annual human rabies mortality from a 2015 study is as high as 59,000 throughout 150 countries. In human rabies, more than 95% of the cases are due to dog bites, making the elimination of canine rabies a global priority by fighting the disease at its animal source. World Health Organization (WHO), World Organization for Animal Health (OIE), Food and Agriculture Organization (FAO) of the United Nations, and the Global Alliance for Rabies Control (GARC) have warranted the One Health framework with the objective of complete eradication of dog-related human rabies by the year 2030. In an effort to rationalise the One Health approach, this scoping review found 17 studies on assessing the effectiveness of control interventions of human and canine rabies. Different strategies were implemented based on the endemicity of rabies in a particular country. Overall, the combined strategies using the One Health approach, which allows effective participation and communication between different agencies, have shown promising results in reducing rabies cases. These strategies will hopefully realise the goal in the Global Strategic Plan to achieve zero canine-mediated human rabies death by the year 2030.

scholarly journals Supporting drug development for neglected tropical diseases using mathematical modelling

2021 ◽  
Author(s):  
Martin Walker ◽  
Jonathan I D Hamley ◽  
Philip Milton ◽  
Frédéric Monnot ◽  
Sally Kinrade ◽  
...  
Keyword(s):  
Drug Development ◽  
Mathematical Modelling ◽  
Neglected Tropical Diseases ◽  
Public Health Problem ◽  
World Health ◽  
Tropical Diseases ◽  
Resource Saving ◽  
Preventive Chemotherapy ◽  
Health Organization ◽  
Chemotherapy Strategy

Abstract Drug-based interventions are at the heart of global efforts to reach elimination as a public health problem (trachoma, soil-transmitted helminthiases, schistosomiasis, lymphatic filariasis) or elimination of transmission (onchocerciasis) for five of the most prevalent neglected tropical diseases tackled via the World Health Organization preventive chemotherapy strategy. While for some of these diseases there is optimism that currently available drugs will be sufficient to achieve the proposed elimination goals, for others—particularly onchocerciasis—there is a growing consensus that novel therapeutic options will be needed. Since in this area no high return of investment is possible, minimizing wasted money and resources is essential. Here, we use illustrative results to show how mathematical modelling can guide the drug development pathway, yielding resource-saving and efficiency payoffs, from the refinement of target product profiles and intended context of use, to the design of clinical trials.

scholarly journals Evolution of Rabies in South America and Inter-Species Dynamics (2009–2018)

2021 ◽  
Vol 6 (2) ◽  
pp. 98
Author(s):  
Mauro Meske ◽  
Angela Fanelli ◽  
Felipe Rocha ◽  
Lina Awada ◽  
Paula Caceres Soto ◽  
...  
Keyword(s):  
Spatial Distribution ◽  
South America ◽  
Neglected Tropical Diseases ◽  
Animal Health ◽  
World Health ◽  
Epidemiological Surveillance ◽  
Health Concern ◽  
Antigenic Variant ◽  
The North ◽  
The World

Rabies is listed as one of the World Health Organisation’s (WHO) Neglected Tropical Diseases Worldwide, with a significant impact in South America. This paper explores the dynamics of rabies cases in humans, pets (dogs and cats), livestock and wildlife (bats in particular) in South America during the period 2009–2018. The data used in this study were derived from the two main databases for rabies in South America: the OIE-WAHIS from the World Organisation for Animal Health (OIE) and PANAFTOSA’s Regional Information System for the Epidemiological Surveillance of Rabies (SIRVERA). Being a neglected disease with possible underreporting in some areas, the reported rabies cases may not always represent the real disease burden. The analysis focuses on the evolution of the number of cases in time and their spatial distribution, as well as on the main source of infections in humans, determined by laboratory assays of the antigenic variant or through epidemiological investigations. Additionally, Generalised Linear Mixed Models (GLMM) were used to evaluate the risk factors associated with the occurrence of human cases. Our results show that the highest impact of the disease in terms of number of cases was reported on livestock, while the overall number of cases (in animals and humans) progressively decreased along the study period. The spatial distribution of rabies in livestock showed two main clusters in the north-western (mainly Colombia) and in the south-eastern part of the affected area (Brazil), and a third smaller cluster in Peru. A cluster in dogs was observed in Bolivia. Out of the 192 human cases reported during the study period, 70% of them were transmitted by bats. The number of human cases reported during the study period were significantly associated with the number of rabies cases reported in livestock, pets and wildlife. Despite the overall decreasing case report rate, the disease still represents a major animal and public health concern in South America, and new strategies for compiling systematic information, networking and education are needed, as well as the education and training of veterinary staff.

scholarly journals Onchocerciasis drug development: from preclinical models to humans

2021 ◽  
Author(s):  
Adela Ngwewondo ◽  
Ivan Scandale ◽  
Sabine Specht
Keyword(s):  
Drug Development ◽  
Neglected Tropical Diseases ◽  
Clinical Stage ◽  
Safety Margin ◽  
New Drugs ◽  
World Health ◽  
Program Goal ◽  
Medical Needs ◽  
Disease Elimination ◽  
Development Pipeline

Abstract Twenty diseases are recognized as neglected tropical diseases (NTDs) by World Health Assembly resolutions, including human filarial diseases. The end of NTDs is embedded within the Sustainable Development Goals for 2030, under target 3.3. Onchocerciasis afflicts approximately 20.9 million people worldwide with > 90% of those infected residing in Africa. Control programs have made tremendous efforts in the management of onchocerciasis by mass drug administration and aerial larviciding; however, disease elimination is not yet achieved. In the new WHO roadmap, it is recognized that new drugs or drug regimens that kill or permanently sterilize adult filarial worms would significantly improve elimination timelines and accelerate the achievement of the program goal of disease elimination. Drug development is, however, handicapped by high attrition rates, and many promising molecules fail in preclinical development or in subsequent toxicological, safety and efficacy testing; thus, research and development (R&D) costs are, in aggregate, very high. Drug discovery and development for NTDs is largely driven by unmet medical needs put forward by the global health community; the area is underfunded and since no high return on investment is possible, there is no dedicated drug development pipeline for human filariasis. Repurposing existing drugs is one approach to filling the drug development pipeline for human filariasis. The high cost and slow pace of discovery and development of new drugs has led to the repurposing of “old” drugs, as this is more cost-effective and allows development timelines to be shortened. However, even if a drug is marketed for a human or veterinary indication, the safety margin and dosing regimen will need to be re-evaluated to determine the risk in humans. Drug repurposing is a promising approach to enlarging the pool of active molecules in the drug development pipeline. Another consideration when providing new treatment options is the use of combinations, which is not addressed in this review. We here summarize recent advances in the late preclinical or early clinical stage in the search for a potent macrofilaricide, including drugs against the nematode and against its endosymbiont, Wolbachia pipientis.

scholarly journals Anthelmintic drug discovery: target identification, screening methods and the role of open science

2020 ◽  
Vol 16 ◽  
pp. 1203-1224 ◽  
Author(s):  
Frederick A Partridge ◽  
Ruth Forman ◽  
Carole J R Bataille ◽  
Graham M Wynne ◽  
Marina Nick ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Neglected Tropical Diseases ◽  
Open Science ◽  
New Drugs ◽  
World Health ◽  
Neglected Diseases ◽  
Screening Methods ◽  
Screening Programs ◽  
Anthelmintic Drug ◽  
Compound Screening

Helminths, including cestodes, nematodes and trematodes, are a huge global health burden, infecting hundreds of millions of people. In many cases, existing drugs such as benzimidazoles, diethylcarbamazine, ivermectin and praziquantel are insufficiently efficacious, contraindicated in some populations, or at risk of the development of resistance, thereby impeding progress towards World Health Organization goals to control or eliminate these neglected tropical diseases. However, there has been limited recent progress in developing new drugs for these diseases due to lack of commercial attractiveness, leading to the introduction of novel, more efficient models for drug innovation that attempt to reduce the cost of research and development. Open science aims to achieve this by encouraging collaboration and the sharing of data and resources between organisations. In this review we discuss how open science has been applied to anthelmintic drug discovery. Open resources, including genomic information from many parasites, are enabling the identification of targets for new antiparasitic agents. Phenotypic screening remains important, and there has been much progress in open-source systems for compound screening with parasites, including motility assays but also high content assays with more detailed investigation of helminth physiology. Distributed open science compound screening programs, such as the Medicines for Malaria Venture Pathogen Box, have been successful at facilitating screening in diverse assays against many different parasite pathogens and models. Of the compounds identified so far in these screens, tolfenpyrad, a repurposed insecticide, shows significant promise and there has been much progress in creating more potent and selective derivatives. This work exemplifies how open science approaches can catalyse drug discovery against neglected diseases.

scholarly journals ADVERSE DRUG REACTIONS: AN OVERVIEW OF THE OLD AND CONTINUOUS CHALLENGE TO DRUG THERAPY AND DEVELOPMENT

2012 ◽  
Vol 1 ◽  
Author(s):  
Abdelbaset A Elzagallaai
Keyword(s):  
Drug Therapy ◽  
Drug Development ◽  
Adverse Drug Reactions ◽  
Hospital Admissions ◽  
Current Knowledge ◽  
The United States ◽  
World Health ◽  
Drug Reactions ◽  
Major Health Problem ◽  
Health Organization

Adverse drug reactions (ADRs) represent a major health problem worldwide and constitute a big challengeto drug therapy and the drug development process. ADRs are responsible for 3% of total hospital admissions and occur in 10 to 20% of hospitalized patients. It has been estimated that ADRs account for at least 100,000 deaths annually in the United States alone ranking them as the fifth leading cause of death. According to the World Health Organization definition an ADR is a noxious and unintended response to a drug that occurs at a dose normally used in man for prophylaxis, diagnosis or therapy. This commonly used definition, however, excludes other drug therapy consequences such as drug abuse, accidental and inadvertent drug overdose and therapeutic failure. ADRs are classified into two main groups: Type A, which are predictable from the drugs’ normal pharmacological actions and are dose dependent and Type B, which are unpredictable, unrelated to the drugs’ pharmacology and do not have clear dose dependency. This is an overview of the currently used definitions and classifications of ADRs in clinical pharmacology and toxicology. Specific relevant examples are cited and some important points are discussed in the light of current knowledge. A special emphasis is made on the importance of ADRs in clinical drug therapy and drug development, which are the areas where ADRs play the most significant role.

scholarly journals Human african trypanosomiasis: current standing and challenges

2020 ◽  
Vol 49 (3) ◽  
Author(s):  
Isabel Theresa Holanda-Freitas ◽  
Marli Do Carmo Cupertino ◽  
Elizária C. dos Santos ◽  
Lisa Oliveira ◽  
Mauro Geller ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Human African Trypanosomiasis ◽  
Vaccine Development ◽  
Neglected Tropical Diseases ◽  
Tsetse Fly ◽  
World Health ◽  
Clinical Aspects ◽  
Neglected Diseases ◽  
African Trypanosomiasis ◽  
African Countries

Human African trypanosomiasis (HAT) caused by the protozoan Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, and transmitted by the tsetse fly (genus Glossina), affects 36 Sub-Saharan African countries with considerable public health impact.  Despite approximately 15,000 infected individuals and 70 million at risk, in recent years the World Health Organization has mentioned removal of HAT from the list of Neglected Tropical Diseases by 2020, due to the decrease in cases over the last two decades. When untreated, the disease presents high lethality rates and the available treatments are complicated to administer, highly toxic, and do not guarantee cure, especially in the advanced stages of the disease. Further, there is no prospect for vaccine development in the near future. The present review compiles information on the history of the clinical aspects of HAT, as well as its epidemiology, diagnosis, therapy, and prophylaxis, as well as updating information on the current panorama and perspectives regarding the disease.KEY WORDS: African Trypanosomiasis; neglected diseases; Trypanosoma brucei.

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