Original algorithms for the detection of cardiovascular involvement of neglected tropical diseases.

INTRODUCTION: Neglected tropical diseases (NTDs) introduce considerable morbidity and mortality on a global scale, directly impacting over 1 billion individuals as well as their families and communities. Afflicted individuals may have limited access to resources and care in these regions, contributing to a high proportion of chronic, progressive, and systemic disease. The cardiovascular system is at particular risk of demise for several NTDs, yet remains largely unstudied due in part to the lack of robust data collection mechanisms in the most impacted regions. AREAS COVERED: The present review is a part of the Neglected Tropical Diseases and other Infectious Diseases affecting the Heart (NET-Heart) Project, aiming at summarizing the current knowledge on cardiovascular implications of NTDs and providing diagnostic as well as management recommendations which can be tailored to low-resource settings. The diagnostic and management algorithms of 13 unique NTDs are presented and summarized. EXPERT OPINION: Recognizing cardiac manifestations of NTDs can significantly alter disease trajectory and all physicians benefit from improved knowledge about NTDs. Great potential exists to advance patient care by improving data collection, communication, and international collaboration.

Neglected tropical disease (NTD) diagnostics: current development and operations to advance control.

Neglected tropical diseases (NTDs) have become important public health threats that require multi-faceted control interventions. As late treatment and management of NTDs contribute significantly to the associated burdens, early diagnosis becomes an important component for surveillance and planning effective interventions. This review identifies common NTDs and highlights the progress in the development of diagnostics for these NTDs. Leveraging existing technologies to improve NTD diagnosis and improving current operational approaches for deployment of developed diagnostics are crucial to achieving the 2030 NTD elimination target. Point-of-care NTD (POC-NTD) diagnostic tools are recommended preferred diagnostic options in resource-constrained areas for mapping risk zones and monitoring treatment efficacy. However, few are currently available commercially. Technical training of remote health care workers on the use of POC-NTD diagnostics, and training of health workers on the psychosocial consequences of these diagnostics are critical in harnessing POC-NTD diagnostic potential. While the COVID-19 pandemic has challenged the possibility of achieving NTD elimination in 2030 due to the disruption of healthcare services and dwindling financial support for NTDs, the possible contribution of NTDs in exacerbating COVID-19 pandemic should motivate NTD health system strengthening.

Screening for Neglected Tropical Diseases and other infections in African refugees and asylum seekers in Rome and Lazio region, Italy.

BACKGROUND: Few reliable data are available on Neglected Tropical Diseases (NTDs) and other infections among African refugees and asylum seekers in Italy. We aimed to estimate the prevalence of NTDs and other infections in a large cohort of African refugees and asylum seekers living in reception centers in Lazio, Italy. MATERIAL AND METHODS: This is an observational, prospective prevalence study on infectious diseases in a large population of African refugees and asylum seekers (936 overall) consecutively enrolled for screening purpose at the Infectious and Tropical diseases outpatient clinic of the National Institute of Migrant and Poverty (INMP), Rome from August 2019 to December 2020. RESULTS: We found a prevalence of 8.8 % and 31 % for Strongyloides and schistosoma infection, respectively, while the prevalence of human immunodeficiency virus (HIV) infection was 0.7 %, HCV antibodies 2.5%, hepatitis B virus surface antigen 10.8 % and syphilis serological tests 2.9 %. CONCLUSION: Strongyloidiasis and schistosomiasis are highly prevalent among African refugees and asylum seekers in Italy, in contrast to communicable diseases (with the exception of hepatitis B). Raising awareness of NTDs among health professionals and implementing guidelines seems to be of paramount importance to prevent these diseases and their sufferers from becoming even more "neglected".

Subcutaneous mycoses: Endemic but neglected among the Neglected Tropical Diseases in Ethiopia.

BACKGROUND: Subcutaneous (deep) mycoses are a chronic infectious disease of the skin and underlying structures endemic in tropical countries. The disease has serious medical and socioeconomic consequences for patients, communities and health services in endemic areas. The inclusion of mycetoma and other subcutaneous mycoses in the list of Neglected Tropical Diseases by WHO highlights the need to assess the burden of these diseases and establish control programs where necessary. In Ethiopia no strategies can be devised because of a lack of epidemiologic information. To address this evidence gap, we performed a national rapid assessment of the geographic distribution of subcutaneous mycoses. METHODOLOGY: We conducted a rapid retrospective assessment using hospital records to identify all suspected and confirmed cases of subcutaneous mycoses in 13 referral hospitals across the country between 2015 and 2022. In each hospital the logbooks were reviewed for diagnoses of subcutaneous mycosess, as diagnosed per routine practice. Descriptive analysis was done. RESULT: From 13 hospitals we extracted 143 cases of subcutaneous mycoses, registered from July 2018 to September 2022. 118 (82.5%) patients were diagnosed as mycetoma, 21 (14.7%) as chromoblastomycosis and the remaining 4 (2.8%) as sporotrichosis. The mean age of patients was 35.8 years (SD = 14.5). 101 (70.6%) patients were male and 96 (67.1%) patients were farmers. 64 (44.8%) cases were from the Tigray regional state. 56 (65.9%) patients had information on diagnostic microscopic evaluation: for mycetoma histopathologic evaluation and fine needle aspiration cytology had a higher positivity rate while for chromoblastomycosis potassium hydroxide (KOH) staining had a better yield. The main clinical presentations were nodules, sinuses and infiltrative plaques on the skin. Radiologic findings of bone involvement was present in some. CONCLUSIONS: Mycetoma and other subcutaneous mycoses are endemic in Ethiopia, with cases reported from almost all regions with the highest cases numbers reported from the northern part of the country. A routine program and systems should be developed to identify and document the burden of subcutaneous fungal infections in the country. Diagnosis and treatment guidelines should be developed.

Deep learning for AI-based diagnosis of skin-related neglected tropical diseases: A pilot study.

BACKGROUND: Deep learning, which is a part of a broader concept of artificial intelligence (AI) and/or machine learning has achieved remarkable success in vision tasks. While there is growing interest in the use of this technology in diagnostic support for skin-related neglected tropical diseases (skin NTDs), there have been limited studies in this area and fewer focused on dark skin. In this study, we aimed to develop deep learning based AI models with clinical images we collected for five skin NTDs, namely, Buruli ulcer, leprosy, mycetoma, scabies, and yaws, to understand how diagnostic accuracy can or cannot be improved using different models and training patterns. METHODOLOGY: This study used photographs collected prospectively in Côte d'Ivoire and Ghana through our ongoing studies with use of digital health tools for clinical data documentation and for teledermatology. Our dataset included a total of 1,709 images from 506 patients. Two convolutional neural networks, ResNet-50 and VGG-16 models were adopted to examine the performance of different deep learning architectures and validate their feasibility in diagnosis of the targeted skin NTDs. PRINCIPAL FINDINGS: The two models were able to correctly predict over 70% of the diagnoses, and there was a consistent performance improvement with more training samples. The ResNet-50 model performed better than the VGG-16 model. A model trained with PCR confirmed cases of Buruli ulcer yielded 1-3% increase in prediction accuracy across all diseases, except, for mycetoma, over a model which training sets included unconfirmed cases. CONCLUSIONS: Our approach was to have the deep learning model distinguish between multiple pathologies simultaneously-which is close to real-world practice. The more images used for training, the more accurate the diagnosis became. The percentages of correct diagnosis increased with PCR-positive cases of Buruli ulcer. This demonstrated that it may be better to input images from the more accurately diagnosed cases in the training models also for achieving better accuracy in the generated AI models. However, the increase was marginal which may be an indication that the accuracy of clinical diagnosis alone is reliable to an extent for Buruli ulcer. Diagnostic tests also have their flaws, and they are not always reliable. One hope for AI is that it will objectively resolve this gap between diagnostic tests and clinical diagnoses with the addition of another tool. While there are still challenges to be overcome, there is a potential for AI to address the unmet needs where access to medical care is limited, like for those affected by skin NTDs.

Burden of neglected tropical diseases and access to medicine and diagnostics in Ethiopia: a scoping review.

BACKGROUND: More than 1.7 billion people are affected by neglected tropical diseases (NTDs) worldwide. Forty percent of the NTD-affected people live in Africa with the poorest, most vulnerable, and hard to reach geographical areas. The NTDs cause significant social and economic burden and deepen marginalization and stigmatization. The World Health Organization's current roadmap for NTD aims to prevent, control, eliminate, or eradicate 20 tropical diseases. Ethiopia experiences a high burden of these diseases, but current access to diagnostics, medicine, and/or care has been little explored to inform the country's NTD strategic plan. The overall purpose of the scoping review was to map and characterize the burden of NTDs and challenges in access to diagnostics, medicine, and/or care in Ethiopia. METHODS: A systematic search of evidence was conducted in PubMed, Cochrane Library, and Google Scholar from January 2000 until May 2022, without restrictions of language or study design. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review was followed for screening of studies. Key findings were extracted and narrated qualitatively. RESULTS: The search resulted in 4532 articles, of which 105 met the inclusion criteria and were included in the scoping review under three themes: burden of NTDs, access to diagnostics, medicine and/or care, and key barriers. Although gains have been made in the prevention and control of NTDs in Ethiopia, the burden remains high, and progress in access to diagnostics, medicine/drugs, and/or care is very slow. Poverty, poor quality of life, and underfunding of NTD programs decelerate the process of NTD elimination program in the country. CONCLUSIONS: The scoping review identified a considerable number of studies on the burden of NTDs in Ethiopia and strategies for diagnosis, treatment, and/or care; however, there is a paucity of evidence on the suitability and potential benefits of novel diagnostic technologies and medicines in the country. A regular review and analysis of such country-level evidence is important to inform the country NTDs roadmap and local implementation strategies.

The development, implementation, and evaluation of an optimal model for the case detection, referral, and case management of Neglected Tropical Diseases.

BACKGROUND: People affected by Neglected Tropical Diseases (NTDs), specifically leprosy, Buruli ulcer (BU), yaws, and lymphatic filariasis, experience significant delays in accessing health services, often leading to catastrophic physical, psychosocial, and economic consequences. Global health actors have recognized that Sustainable Development Goal 3:3 is only achievable through an integrated inter and intra-sectoral response. This study evaluated existing case detection and referral approaches in Liberia, utilizing the findings to develop and test an Optimal Model for integrated community-based case detection, referral, and confirmation. We evaluate the efficacy of implementing the Optimal Model in improving the early diagnosis of NTDs, thus minimizing access delays and reducing disease burden. METHODS: We used a participatory action research approach to develop, implement, and evaluate an Optimal Model for the case detection, referral, and management of case management NTDs in Liberia. We utilized qualitative and quantitative methods throughout the cycle and implemented the model for 12 months. RESULTS: During the implementation of our optimal model, the annual number of cases detected increased compared to the previous year. Cases were detected at an earlier stage of disease progression, however; gendered dynamics in communities shape the case identification process for some individuals. Qualitative data showed increased knowledge of the transmission, signs, symptoms, and management options among community health workers (CHW). CONCLUSION: The results provide evidence of the benefits of an integrated approach and the programmatic challenges to improve access to health services for persons affected by NTDs. The effectiveness of an integrated approach depends on a high level of collaboration, joint planning, and implementation embedded within existing health systems infrastructure.

Importance of consultations using mobile teams in the screening and treatment of neglected tropical skin diseases in Benin.

CONTEXT: Since 2013, the World Health Organization has recommended integrated control strategies for neglected tropical diseases (NTDs) with skin manifestations. We evaluated the implementation of an integrated approach to the early detection and rapid treatment of skin NTDs based on mobile clinics in the Ouémé and Plateau areas of Benin. METHODS: This descriptive cross-sectional study was performed in Ouémé and Plateau in Benin from 2018 to 2020. Consultations using mobile teams were performed at various sites selected by reasoned choice based on the epidemiological data of the National Program for the Control of Leprosy and Buruli Ulcer. All individuals presenting with a dermatological lesion who voluntarily approached the multidisciplinary management team on the day of consultation were included. The information collected was kept strictly anonymous and was entered into an Excel 2013 spreadsheet and analyzed with Stata 11 software. RESULTS: In total, 5,267 patients with various skin conditions consulted the medical team. The median age of these patients was 14 years (IQR: 7-34 years). We saw 646 (12.3%) patients presenting NTDs with skin manifestations, principally scabies, in 88.4% (571/646), followed by 37 cases of Buruli ulcer (5.8%), 22 cases of leprosy (3.4%), 15 cases of lymphatic filariasis (2.3%) and one case of mycetoma (0.2%). We detected no cases of yaws. CONCLUSION: This sustainable approach could help to decrease the burden of skin NTDs in resource-limited countries.

Low-Cost Microfluidic Systems for Detection of Neglected Tropical Diseases.

Neglected tropical diseases (NTDs) affect tropical and subtropical countries and are caused by viruses, bacteria, protozoa, and helminths. These kinds of diseases spread quickly due to the tropical climate and limited access to clean water, sanitation, and health care, which make exposed people more vulnerable. NTDs are reported to be difficult and inefficient to diagnose. As mentioned, most NTDs occur in countries that are socially vulnerable, and the lack of resources and access to modern laboratories and equipment intensify the difficulty of diagnosis and treatment, leading to an increase in the mortality rate. Portable and low-cost microfluidic systems have been widely applied for clinical diagnosis, offering a promising alternative that can meet the needs for fast, affordable, and reliable diagnostic tests in developing countries. This review provides a critical overview of microfluidic devices that have been reported in the literature for the detection of the most common NTDs over the past 5 years.

A mixed methods evaluation of an integrated training package for skin neglected tropical diseases in Kaduna and Ogun, Nigeria.

BACKGROUND: The overall burden of neglected tropical diseases (NTDs) affecting the skin is undetermined. Skin conditions are among the top 10 causes of disability worldwide. Affected persons seek treatment at advanced stages of the disease, resulting in morbidity and disability. We developed and evaluated an integrated training intervention for early case detection, referral and management of skin NTDs in two states in Nigeria. METHODS: This was a mixed-methods study using participatory approaches to develop specific skin algorithms and training packages for community and primary level health workers. This supported the identification, referral and clinical diagnosis of suspected cases. We used Kirkpatrick's model to evaluate the training package. RESULTS: Participants' knowledge improved after the 2-months intervention. Across both states, knowledge retention appeared more robust for cadres at all levels: state, local government area and primary healthcare. All (100%) participants mentioned that the training assisted them in detecting, referring and managing skin NTDs. Training was understood by participants and training materials were easy to understand. Materials were also effective in educating community members about the symptoms of NTDs and supported referral to facilities for appropriate management. CONCLUSIONS: Community implementers can be trained and supervised to detect people affected by skin NTDs and support appropriate management within the existing patient care pathway.

Molecular Detection of Neglected Tropical Diseases: The Case for Automated Near-Point-of-Care Diagnosis of Leishmaniasis.

Neglected tropical diseases affect those in poorer nations disproportionately across the globe. One example of these, leishmaniasis, is a debilitating and potentially fatal parasitic infection. Molecular detection of this disease can provide accurate and fast diagnosis, and with near point-of-care technologies, detection can be provided in many health-care settings. Traditionally, the perceived limitations to such detection methods have hindered their provision to resource-limited nations, but new technologies and techniques are helping to overcome these perceptions. The current pandemic offers an opportunity to maintain and develop further advances, ensuring molecular diagnostics are accessible to all.

A combined effort of 11 laboratories in the WHO African region to improve quality of Buruli ulcer PCR diagnosis: The "BU-LABNET".

Buruli ulcer is one of the 20 neglected tropical diseases in the world. This necrotizing hypodermitis is a chronic debilitating disease caused by an environmental Mycobacterium ulcerans. At least 33 countries with tropical, subtropical and temperate climates have reported Buruli ulcer in African countries, South America and Western Pacific regions. Majority of cases are spread across West and Central Africa. The mode of transmission is unclear, hindering the implementation of adequate prevention for the population. Currently, early diagnosis and treatment are crucial to minimizing morbidity, costs and preventing long-term disability. Biological confirmation of clinical diagnosis of Buruli ulcer is essential before starting chemotherapy. Indeed, differential diagnosis are numerous and Buruli ulcer has varying clinical presentations. Up to now, the gold standard biological confirmation is the quantitative PCR, targeting the insertion sequence IS2404 of M. ulcerans performed on cutaneous samples. Due to the low PCR confirmation rate in endemic African countries (under 30% in 2018) for numerous identified reasons within this article, 11 laboratories decided to combine their efforts to create the network "BU-LABNET" in 2019. The first step of the network was to harmonize the procedures and ship specific reagents to each laboratory. With this system in place, implementation of these procedures for testing and follow-up was easy and the laboratories were able to carry out their first quality control with a very high success rate. It is now time to integrate other neglected tropical diseases to this platform, such as yaws or leprosy.

Diagnostics to support mycetoma management-Development of two target product profiles.

OBJECTIVE: Mycetoma is a neglected tropical disease caused by more than 70 different microorganisms and identified by the WHO as one of the high-priority diseases for developing diagnostic tests. To ensure the production of diagnostic assays for use by clinical staff in endemic regions, target product profiles (TPPs) were designed. METHODS: We describe the development of two TPPs: one for a diagnostic test able to identify the causative agent of mycetoma and another that would determine when treatment could be stopped. The TPPs were developed by considering product use, design, performance, product configuration and costs. RESULTS: Version 1.0 TPPs for two uses were posted by WHO for a 1-month online public consultation on 25 October 2021, and the final TPP was posted online on 5 May 2022. CONCLUSION: A major difficulty encountered in developing both TPPs was the large number of agents able to cause mycetoma and the lack of specific biomarkers for most of them.

Revisiting scrub typhus: A neglected tropical disease.

Scrub typhus is an under diagnosed re-emerging vector borne disease caused by an intracellular gram negative bacteria, Orientia. The disease is commonly prevalent in rural and hilly areas of Tsutsugumashi triangle. The diagnosis of the disease is very challenging due to similarity of its early symptoms with other febrile illnesses, like dengue and COVID 19, as well as non-availability of rapid, reliable and cost-effective methods. Moreover, the diverse clinical presentation in severe cases make it significant health problem. The occupational and behavioral risks responsible for the transmission lead to urgent need of vaccine development against the disease. The complete knowledge about its pathogenesis and the interaction with host's immune cells may help the scientists in developing the appropriate diagnostic methods as well as the vaccines.

Diagnostics to support the eradication of yaws-Development of two target product profiles.

BACKGROUND: Yaws is targeted for eradication by 2030, using a strategy based on mass drug administration (MDA) with azithromycin. New diagnostics are needed to aid eradication. Serology is currently the mainstay for yaws diagnosis; however, inaccuracies associated with current serological tests makes it difficult to fully assess the need for and impact of eradication campaigns using these tools. Under the recommendation of the WHO Diagnostic Technical Advisory Group (DTAG) for Neglected Tropical Diseases(NTDs), a working group was assembled and tasked with agreeing on priority use cases for developing target product profiles (TPPs) for new diagnostics tools. METHODOLOGY AND PRINCIPAL FINDINGS: The working group convened three times and established two use cases: identifying a single case of yaws and detecting azithromycin resistance. One subgroup assessed the current diagnostic landscape for yaws and a second subgroup determined the test requirements for both use cases. Draft TPPs were sent out for input from stakeholders and experts. Both TPPs considered the following parameters: product use, design, performance, configuration, cost, access and equity. To identify a single case of yaws, the test should be able to detect an analyte which confirms an active infection with at least 95% sensitivity and 99.9% specificity. The high specificity was deemed important to avoid a high false positive rate which could result in unnecessary continuation or initiation of MDA campaigns. If used in settings where the number of suspected cases is low, further testing could be considered to compensate for imperfect sensitivity and to improve specificity. The test to detect azithromycin resistance should be able to detect known genetic resistance mutations with a minimum sensitivity and specificity of 95%, with the caveat that all patients with suspected treatment failure should be treated as having resistant yaws and offered alternative treatment. CONCLUSIONS: The TPPs developed will provide test developers with guidance to ensure that novel diagnostic tests meet identified public health needs.

Quantifying Population Burden and Effectiveness of Decentralized Surveillance Strategies for Skin-Presenting Neglected Tropical Diseases, Liberia.

We evaluated programmatic approaches for skin neglected tropical disease (NTD) surveillance and completed a robust estimation of the burden of skin NTDs endemic to West Africa (Buruli ulcer, leprosy, lymphatic filariasis morbidity, and yaws). In Maryland, Liberia, exhaustive case finding by community health workers of 56,285 persons across 92 clusters identified 3,241 suspected cases. A total of 236 skin NTDs (34.0 [95% CI 29.1-38.9]/10,000 persons) were confirmed by midlevel healthcare workers trained using a tailored program. Cases showed a focal and spatially heterogeneous distribution. This community health worker‒led approach showed a higher skin NTD burden than prevailing surveillance mechanisms, but also showed high (95.1%) and equitable population coverage. Specialized training and task-shifting of diagnoses to midlevel health workers led to reliable identification of skin NTDs, but reliability of individual diagnoses varied. This multifaceted evaluation of skin NTD surveillance strategies quantifies benefits and limitations of key approaches promoted by the 2030 NTD roadmap of the World Health Organization.