Diagnosing point-of-care diagnostics for neglected tropical diseases

Inadequate and nonintegrated diagnostics are the Achilles’ heel of global efforts to monitor, control, and eradicate neglected tropical diseases (NTDs). While treatment is often available, NTDs are endemic among marginalized populations, due to the unavailability or inadequacy of diagnostic tests that cause empirical misdiagnoses. The need of the hour is early diagnosis at the point-of-care (PoC) of NTD patients. Here, we review the status quo of PoC diagnostic tests and practices for all of the 24 NTDs identified in the World Health Organization’s (WHO) 2021–2030 roadmap, based on their different diagnostic requirements. We discuss the capabilities and shortcomings of current diagnostic tests, identify diagnostic needs, and formulate prerequisites of relevant PoC tests. Next to technical requirements, we stress the importance of availability and awareness programs for establishing PoC tests that fit endemic resource-limited settings. Better understanding of NTD diagnostics will pave the path for setting realistic goals for healthcare in areas with minimal resources, thereby alleviating the global healthcare burden.     

Canadian contributions to research on neglected tropical diseases

BackgroundThe World Health Organization’s (WHO) Neglected Tropical Disease (NTD) Road Map for 2021–2030 was recently endorsed by all member states at the World Health Assembly in November 2020. Although only 3 of the 20 NTDs are endemic in Canada (i.e., echinococcosis, rabies, and scabies), the Canadian research community has contributed to advancing the knowledge base of all 20 NTDs. Previous research comprehensively detailed Canadian research on 11 NTDs between 1950 and 2010 using a network analysis approach. The specific objective of the present analysis was to update the publication record over the last decade (2010–2019) to include all 20 NTDs.Materials and methodsA bibliometric analysis was conducted in Scopus and Web of Science databases (for English or French articles published between January 1, 2010 and December 31, 2019) using appropriate search terms for each of the 20 NTDs and where at least 1 of the authors had a Canadian institution address. A 21st search was added to include publications including multiple NTDs or a discussion of NTDs in general. Following assessment of inclusion and exclusion criteria, 2 reviewers independently screened all abstracts, with discordant observations rereviewed to arrive at an agreement. Duplicates were removed.ResultsA total of 1,790 publications were retrieved (1,738 with a disease–specific NTD focus and 52 with a general NTD focus, resulting in 1,659 unique publications), giving an average of over 160 articles per year. Over 80% were classified as full–length research articles. The top 3 journals in terms of frequency were PLOS Neglected Tropical Diseases, PLOS ONE, and the American Journal of Tropical Medicine and Hygiene. Authors’ institutions were from all Canadian provinces. While all 20 NTDs were addressed in these publications, the 5 most commonly studied were leishmaniasis, dengue fever and chikungunya, Chagas disease, soil–transmitted helminthiases, and rabies.ConclusionsCanadian researchers across the country have contributed to the evidence base of all 20 NTDs, publishing an average of over 160 publications per year between 2010 and 2019. As WHO NTD Road Map 2021–2030 rolls out globally, the Canadian research community, in collaboration with its partners and in solidarity with people living in vulnerable circumstances in endemic regions worldwide, is well positioned to meet future research challenges so that the goal of eliminating the disease burden attributable to NTDs can be achieved.     

Community-driven interventions can revolutionise control of neglected tropical diseases

Whether global health interventions target diseases (vertical), systems (horizontal) or both (diagonal), they must address the challenge of delivering services in very remote areas of poor countries with inadequate infrastructure. The primacy of this challenge has been underscored by persistent service-delivery difficulties despite several large financial commitments - the latest, US $363 million in the January 2012 London Declaration. Community-driven approaches, pioneered in river blindness control, show that engaging communities can maximise access and performance. This experience should inform a paradigm shift in disease control whereby communities are empowered to extend health service access themselves.     

The field-testing of a novel integrated mapping protocol for neglected tropical diseases

Background

Vertical control and elimination programs focused on specific neglected tropical diseases (NTDs) can achieve notable success by reducing the prevalence and intensity of infection. However, many NTD-endemic countries have not been able to launch or scale-up programs because they lack the necessary baseline data for planning and advocacy. Each NTD program has its own mapping guidelines to collect missing data. Where geographic overlap among NTDs exists, an integrated mapping approach could result in significant resource savings. We developed and field-tested an innovative integrated NTD mapping protocol (Integrated Threshold Mapping (ITM) Methodology) for lymphatic filariasis (LF), trachoma, schistosomiasis and soil-transmitted helminths (STH).

Methodology/Principal Findings

The protocol is designed to be resource-efficient, and its specific purpose is to determine whether a threshold to trigger public health interventions in an implementation unit has been attained. The protocol relies on World Health Organization (WHO) recommended indicators in the disease-specific age groups. For each disease, the sampling frame was the district, but for schistosomiasis, the sub-district rather than the ecological zone was used. We tested the protocol by comparing it to current WHO mapping methodologies for each of the targeted diseases in one district each in Mali and Senegal. Results were compared in terms of public health intervention, and feasibility, including cost. In this study, the ITM methodology reached the same conclusions as the WHO methodologies regarding the initiation of public health interventions for trachoma, LF and STH, but resulted in more targeted intervention recommendations for schistosomiasis. ITM was practical, feasible and demonstrated an overall cost saving compared with the standard, non-integrated, WHO methodologies.

Conclusions/Significance

This integrated mapping tool could facilitate the implementation of much-needed programs in endemic countries.     

Reconsidering the underestimated burden caused by neglected tropical diseases

It is generally acknowledged that the burden caused by neglected tropical diseases needs to be reassessed. Not only are there several important diseases unaccounted for, but new information suggests they have a more substantial impact on health than initially thought. Looking at the tropical diseases as a group makes sense: they tend to cluster in the same poor populations and, to make progress with their control, they will have to be dealt with in an integrated manner. Measuring the effect of such integrated control is likely to reveal the real impact of tropical diseases on human health and wellbeing.     

Comparing models for early warning systems of neglected tropical diseases

Background

Early warning systems (EWS) are management tools to predict the occurrence of epidemics of infectious diseases. While climate-based EWS have been developed for malaria, no standard protocol to evaluate and compare EWS has been proposed. Additionally, there are several neglected tropical diseases whose transmission is sensitive to environmental conditions, for which no EWS have been proposed, though they represent a large burden for the affected populations.

Methodology/Principal Findings

In the present paper, an overview of the available linear and non-linear tools to predict seasonal time series of diseases is presented. Also, a general methodology to compare and evaluate models for prediction is presented and illustrated using American cutaneous leishmaniasis, a neglected tropical disease, as an example. The comparison of the different models using the predictive R ² for forecasts of “out-of-fit” data (data that has not been used to fit the models) shows that for the several linear and non-linear models tested, the best results were obtained for seasonal autoregressive (SAR) models that incorporate climatic covariates. An additional bootstrapping experiment shows that the relationship of the disease time series with the climatic covariates is strong and consistent for the SAR modeling approach. While the autoregressive part of the model is not significant, the exogenous forcing due to climate is always statistically significant. Prediction accuracy can vary from 50% to over 80% for disease burden at time scales of one year or shorter.

Conclusions/Significance

This study illustrates a protocol for the development of EWS that includes three main steps: (i) the fitting of different models using several methodologies, (ii) the comparison of models based on the predictability of “out-of-fit” data, and (iii) the assessment of the robustness of the relationship between the disease and the variables in the model selected as best with an objective criterion.     

Modeling transmission dynamics and control of vector-borne neglected tropical diseases

Neglected tropical diseases affect more than one billion people worldwide. The populations most impacted by such diseases are typically the most resource-limited. Mathematical modeling of disease transmission and cost-effectiveness analyses can play a central role in maximizing the utility of limited resources for neglected tropical diseases. We review the contributions that mathematical modeling has made to optimizing intervention strategies of vector-borne neglected diseases. We propose directions forward in the modeling of these diseases, including integrating new knowledge of vector and pathogen ecology, incorporating evolutionary responses to interventions, and expanding the scope of sensitivity analysis in order to achieve robust results.     

Brazil's neglected tropical diseases: an overview and a report card

Today, the nation of Brazil leads the Western Hemisphere in terms of the number of its citizens living with neglected tropical diseases (NTDs). These diseases continue to trap Brazil's “bottom 20 million” in extreme poverty.