Machine Learning Approaches for Temporal and Spatio-Temporal Covid-19 Forecasting: A Brief Review and a Contribution

In December 2019 an outbreak of a new disease happened, in Wuhan city, China, in which the symptoms were very similar to pneumonia. The disease was attributed to SARS-CoV-2 as the infectious agent and it was called the new coronavirus or Covid-19. In March 2020, the World Health Organization declared a worldwide pandemic of the new coronavirus. We have already counted more than 110 million cases and almost 2.5 million deaths worldwide. In order to assist in decision-making to contain the disease, several scientists around the world have engaged in various efforts, and they have proposed a lot of systems and solutions for tracking, monitoring, and predicting confirmed cases and deaths from Covid-19. Mathematical models help to analyze and understand the evolution of the disease, but understanding the disease was not enough, it was necessary to understand the problem in a quantitative way to lead the decision-making during the pandemic. Several initiatives have made use of Artificial Intelligence, and models were designed using machine learning algorithms with features for temporal and spatio-temporal investigation and prediction of cases of Covid-19. Among the algorithms used are Support Vector Machine (SVM), Random Forest, Multilayer Perceptron (MLP), Graph Neural Networks (GNNs), Ecological Niche Models (ENMs), Long-Short Term Memory Networks (LSTM), linear regression, and others. And these had good results, and to analyze them, the Root Mean Squared Error (RMSE), Log Root Mean Squared Error (RMSLE), correlation coefficient, and others were used as metrics. Covid-19 presents a huge problem to public health worldwide, so it is of utmost importance to investigate it, and with these two approaches it is possible to track not only how the disease evolves but also to know which areas are at risk. And these solutions can help in supporting decision-making by health managers to make the best decisions for the disease that is in the outbreak. This chapter aims to present a literature review and a brief contribution to the use of machine learning methods for temporal and spatio-temporal prediction of Covid-19, using Brazil and its federative units as a case study. From canonical methods to deep networks and hybrid committee-based, approaches will be investigated. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Rabies in a postpandemic world: resilient reservoirs, redoubtable riposte, recurrent roadblocks, and resolute recidivism.

Rabies is an ancient disease. Two centuries since Pasteur, fundamental progress occurred in virology, vaccinology, and diagnostics-and an understanding of pathobiology and epizootiology of rabies in testament to One Health-before common terminological coinage. Prevention, control, selective elimination, and even the unthinkable-occasional treatment-of this zoonosis dawned by the twenty-first century. However, in contrast to smallpox and rinderpest, eradication is a wishful misnomer applied to rabies, particularly post-COVID-19 pandemic. Reasons are minion. Polyhostality encompasses bats and mesocarnivores, but other mammals represent a diverse spectrum of potential hosts. While rabies virus is the classical member of the genus, other species of lyssaviruses also cause the disease. Some reservoirs remain cryptic. Although global, this viral encephalitis is untreatable and often ignored. As with other neglected diseases, laboratory-based surveillance falls short of the notifiable ideal, especially in lower- and middle-income countries. Calculation of actual burden defaults to a flux within broad health economic models. Competing priorities, lack of defined, long-term international donors, and shrinking local champions challenge human prophylaxis and mass dog vaccination toward targets of 2030 for even canine rabies impacts. For prevention, all licensed vaccines are delivered to the individual, whether parenteral or oral-essentially 'one and done'. Exploiting mammalian social behaviors, future 'spreadable vaccines' might increase the proportion of immunized hosts per unit effort. However, the release of replication-competent, genetically modified organisms selectively engineered to spread intentionally throughout a population raises significant biological, ethical, and regulatory issues in need of broader, transdisciplinary discourse. How this rather curious idea will evolve toward actual unconventional prevention, control, or elimination in the near term remains debatable. In the interim, more precise terminology and realistic expectations serve as the norm for diverse, collective constituents to maintain progress in the field.

Recognising the potential of neglected tropical disease programmes as a platform for pandemic preparedness: the Ascend experience.

Living in an increasingly interconnected world, epidemics and pandemics are increasingly likely to be a vista for the future. This, coupled with the likely devastating effects of climate change, means that humanitarian crises are likely to increase. Now, more than ever before, is the time to scale up investment in prevention and preparedness strategies, and to review our current approaches to delivering health services, including those that address neglected tropical diseases. The Ascend West and Central Africa programme has illustrated the importance of innovation, multisector partnerships, resilience and the opportunity for change.

Role of neglected parasitic diseases in the era of COVID-19 pandemics

There are some doubts about the exact relationship between neglected infectious diseases (NIDs) and COVID-19 disease, which remains to be clearly defined. The present review summarized the effect of parasitic infections as the risk factors or protective agents in the COVID-19 pandemic. Parasites could proficiently modulate immune responses. Thus, parasitic infections could have a different impact on the incidence and clinical severity of COVID-19 in different regions of the world. Also, restoring programs to prevent, treat, and control NIDs, in particular helminths, could help in reducing the incidence and mortality of COVID-19 in endemic areas and help to increase vaccination effectiveness. Changes in the gut microbiome associated with helminth infection may have systemic immunomodulatory effects toward suppressing host immune responses, reducing vaccine efficacy and increasing the severity of other infectious diseases. The cytokine storm observed in severe cases of COVID-19 is characterized by a predominance of proinflammatory cytokines, such as IL-6. However, it is possible that helminth infection could change the outcome of infection by modifying the Th2 response to limit the inflammatory component;this would be particularly apparent in areas endemic for helminthic infections, which suggests a possible protective effect against COVID-19. Because parasitic infections affect more than 2 billion people throughout the world, their impact on COVID-19- associated effects on public health could be considerable. Further studies with larger sample sizes would be needed to explore the possible role of neglected parasitic infections in the COVID-19 pandemic.

Elimination of human onchocerciasis: progress report, 2021

This progress report provides an update on the progress made towards eliminating nnchocerciasis (river blindness) by the World Health Organization (WHO) as part of its road map on neglected tropical diseases for 2021-2030. The report highlights that the goal is to eliminate the need for mass drug administration of ivermectin in at least one focus in 34 countries by 2030, in more than 50% of the population in at least 16 countries and in the entire endemic population in at least 12 countries. However, challenges remain in achieving these goals, including incomplete mapping of all transmission zones, co-endemicity of onchocerciasis and loiasis, a potential decrease in sensitivity to ivermectin, uncoordinated cross-border work, suboptimal programme implementation and inadequate technical and financial resources. COVID-19 has also delayed national programmes, with millions of doses of preventive chemotherapy that should have been distributed expiring. The report also provides regional highlights, including that in 2021, 23 countries reported having treated a total of 142.3 million people for onchocerciasis, representing 58.1% of global coverage, and that the African region faces the greatest challenge with 99% of the global burden of the disease in this region.

Characterization of tungiasis infection and morbidity using thermography in Kenya revealed higher disease burden during COVID-19 school closures.

BACKGROUND: Tungiasis is a neglected tropical skin disease caused by the sand flea Tunga penetrans. Female fleas penetrate the skin, particularly at the feet, and cause severe inflammation. This study aimed to characterize disease burden in two highly affected regions in Kenya, to test the use of thermography to detect tungiasis-associated inflammation and to create a new two-level classification of disease severity suitable for mapping, targeting, and monitoring interventions. METHODS: From February 2020 to April 2021, 3532 pupils age 8-14 years were quasi-randomly selected in 35 public primary schools and examined for tungiasis and associated symptoms. Of the infected pupils, 266 were quasi-randomly selected and their households visited, where an additional 1138 family members were examined. Inflammation was assessed using infra-red thermography. A Clinical score was created combining the number of locations on the feet with acute and chronic symptoms and infra-red hotspots. RESULTS: The overall prevalence of tungiasis among all the school pupils who were randomly selected during survey rounds 1 and 3 was 9.3% [95% confidence interval (CI): 8.4-10.3]. Based on mixed effects logistic models, the odds of infection with tungiasis among school pupils was three times higher in Kwale (coastal Kenya) than in Siaya [western Kenya; adjusted odds ratio (aOR) = 0.36, 95% CI: 0.18-0.74]; three times higher in males than in females (aOR = 3.0, 95% CI: 2.32-3.91) and three times lower among pupils sleeping in a house with a concrete floor (aOR = 0.32, 95% CI: 0.24-0.44). The odds of finding an infected person among the household population during surveys before the COVID-19 pandemic was a third (aOR = 0.32, 95% CI: 0.19-0.53) of that when schools were closed due to COVID-19 restrictions and approximately half (aOR = 0.44, 95% CI: 0.29-0.68) in surveys done after school re-opening (round 3). Infection intensity was positively correlated with inflammation as measured by thermography (Spearman's rho = 0.68, P < 0.001) and with the clinical score (rho = 0.86, P < 0.001). Based on the two-level classification, severe cases were associated with a threefold higher level of pain (OR = 2.99, 95% CI: 2.02-4.43) and itching (OR = 3.31, 95% CI: 2.24-4.89) than mild cases. CONCLUSIONS: Thermography was a valuable addition for assessing morbidity and the proposed two-level classification of disease severity clearly separated patients with mild and severe impacts. The burden of tungiasis was considerably higher in households surveyed during COVID-19 restrictions suggesting underlying risks are found in the home environment more than in school.

Financing care for Severe Stigmatizing Skin Diseases (SSSDs) in Liberia: challenges and opportunities.

INTRODUCTION: Neglected tropical diseases (NTDs) are an important global health challenge, however, little is known about how to effectively finance NTD related services. Integrated management in particular, is put forward as an efficient and effective treatment modality. This is a background study to a broader health economic evaluation, seeking to document the costs of integrated case management of NTDs versus standard care in Liberia. In the current study, we document barriers and facilitators to NTD care from a health financing perspective. METHODS: We carried out key informant interviews with 86 health professionals and 16 national health system policymakers. 46 participants were active in counties implementing integrated case management and 40 participants were active in counties implementing standard care. We also interviewed 16 patients and community members. All interviews were transcribed and analysed using the thematic framework approach. FINDINGS: We found that decentralization for NTD financing is not yet achieved - financing and reporting for NTDs is still centralized and largely donor-driven as a vertical programme; government involvement in NTD financing is still minimal, focused mainly on staffing, but non-governmental organisations (NGOs) or international agencies are supporting supply and procurement of medications. Donor support and involvement in NTDs are largely coordinated around the integrated case management. Quantification for goods and budget estimations are specific challenges, given the high donor dependence, particularly for NTD related costs and the government's limited financial role at present. These challenges contribute to stockouts of medications and supplies at clinic level, while delays in payments of salaries from the government compromise staff attendance and retention. For patients, the main challenges are high transportation costs, with inflated charges due to fear and stigma amongst motorbike taxi riders, and out-of-pocket payments for medication during stockouts and food/toiletries (for in-patients). CONCLUSION: Our findings contribute to the limited work on financing of SSSD services in West African settings and provide insight on challenges and opportunities for financing and large costs in accessing care by households, which is also being exacerbated by stigma.

Small molecules containing chalcogen elements (S, Se, Te) as new warhead to fight neglected tropical diseases.

Neglected tropical diseases (NTDs) encompass a group of infectious diseases with a protozoan etiology, high incidence, and prevalence in developing countries. As a result, economic factors constitute one of the main obstacles to their management. Endemic countries have high levels of poverty, deprivation and marginalization which affect patients and limit their access to proper medical care. As a matter of fact, statistics remain uncollected in some affected areas due to non-reporting cases. World Health Organization and other organizations proposed a plan for the eradication and control of the vector, although many of these plans were halted by the COVID-19 pandemic. Despite of the available drugs to treat these pathologies, it exists a lack of effectiveness against several parasite strains. Treatment protocols for diseases such as American trypanosomiasis (Chagas disease), leishmaniasis, and human African trypanosomiasis (HAT) have not achieved the desired results. Unfortunately, these drugs present limitations such as side effects, toxicity, teratogenicity, renal, and hepatic impairment, as well as high costs that have hindered the control and eradication of these diseases. This review focuses on the analysis of a collection of scientific shreds of evidence with the aim of identifying novel chalcogen-derived molecules with biological activity against Chagas disease, leishmaniasis and HAT. Compounds illustrated in each figure share the distinction of containing at least one chalcogen element. Sulfur (S), selenium (Se), and tellurium (Te) have been grouped and analyzed in accordance with their design strategy, chemical synthesis process and biological activity. After an exhaustive revision of the related literature on S, Se, and Te compounds, 183 compounds presenting excellent biological performance were gathered against the different causative agents of CD, leishmaniasis and HAT.

Progress in eliminating onchocerciasis in the WHO region of the Americas: disruption of ivermectin mass drug administration in the Yanomami focus area due to the COVID-19 pandemic

This article describes how the COVID-19 pandemic significantly reduced provision of treatment in the Yanomami focus area (YFA) in 2020, especially in the Bolivarian Republic of Venezuela. The distribution of ivermectin for mass treatment (MDA) to prevent onchocerciasis was affected worldwide by the COVID-19 pandemic in 2020, as were MDA programs for other neglected tropical diseases (NTDs). On 1 April 2020, WHO recommended that mass treatment campaigns, active case-finding, and population-based surveys for NTDs be postponed until further notice to reduce the risk of COVID-19 transmission associated with large-scale community health interventions. The Carter Center, which provides major funding to MDA in the Bolivarian Republic of Venezuela, temporarily halted its activities in 2020 due to an administrative problem and, once the COVID-19 pandemic had taken hold, in order to adhere to WHO recommendations, its own policies, and the policies of other donor organizations. Ivermectin treatment continued to be offered in Brazil, supported by the government, with essential health services such as vaccination and malaria control. On 27 July 2021, WHO released new interim guidance for NTD programs. This included a risk-benefit analysis to figure out if activities could be resumed safely and detailed standards for reducing risk with all known precautions (such as wearing masks, socialdistance, hand sanitizing and/or handwashing, limiting live meetings and group size). The program in the Bolivarian Republic of Venezuela followed these instructions and made a plan to get back to work safely, which was what WHO wanted.

Challenges of addressing neglected tropical diseases amidst the COVID-19 pandemic in Africa: A case of Chagas Disease.

Chagas Disease (CD) is an infectious, neglected tropical disease (NTD) that has affected over 1.7 billion people worldwide. Unfortunately, most countries usually put little effort into mitigating the spread of NTDs, having weak public health approaches, diagnostic delays, and ineffective clinical management guidelines and resources. However, the ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by the coronavirus SARS-CoV-2, exacerbates the impact of NTDs. In this review, we examine the subsequent changes that have been imposed on CD prevention and treatment. Articles from Google Scholar and PubMed were extracted which satisfied our inclusion criteria. From our data, we gather that COVID-19 has - from preventive measures to treating patients - greatly affected every stage in the fight against CD. For instance, co-infection of CD and COVID-19 puts patients at higher risk for cardiomyopathy (i.e., atrial fibrillation, chronic heart failure), yet no clinical guidelines were established for co-infected patients. To mitigate the spread of CD during the COVID-19 pandemic, further investigations on the impacts of co-infections and vaccines that can be developed to treat such conditions are warranted.

SMART-LAMP: A Smartphone-Operated Handheld Device for Real-Time Colorimetric Point-of-Care Diagnosis of Infectious Diseases via Loop-Mediated Isothermal Amplification.

Nucleic acid amplification diagnostics offer outstanding features of sensitivity and specificity. However, they still lack speed and robustness, require extensive infrastructure, and are neither affordable nor user-friendly. Thus, they have not been extensively applied in point-of-care diagnostics, particularly in low-resource settings. In this work, we have combined the loop-mediated isothermal amplification (LAMP) technology with a handheld portable device (SMART-LAMP) developed to perform real-time isothermal nucleic acid amplification reactions, based on simple colorimetric measurements, all of which are Bluetooth-controlled by a dedicated smartphone app. We have validated its diagnostic utility regarding different infectious diseases, including Schistosomiasis, Strongyloidiasis, and COVID-19, and analyzed clinical samples from suspected COVID-19 patients. Finally, we have proved that the combination of long-term stabilized LAMP master mixes, stored and transported at room temperature with our developed SMART-LAMP device, provides an improvement towards true point-of-care diagnosis of infectious diseases in settings with limited infrastructure. Our proposal could be easily adapted to the diagnosis of other infectious diseases.

Rabies in the Tropics.

Purpose of Review: Rabies is an ancient yet still neglected tropical disease (NTD). This review focuses upon highlights of recent research and peer-reviewed communications on the underestimated tropical burden of disease and its management due to the complicated dynamics of virulent viral species, diverse mammalian reservoirs, and tens of millions of exposed humans and animals - and how laboratory-based surveillance at each level informs upon pathogen spread and risks of transmission, for targeted prevention and control. Recent Findings: While both human and rabies animal cases in enzootic areas over the past 5 years were reported to PAHO/WHO and OIE by member countries, still there is a huge gap between these "official" data and the need for enhanced surveillance efforts to meet global program goals. Summary: A review of the complex aspects of rabies perpetuation in human, domestic animal, and wildlife communities, coupled with a high fatality rate despite the existence of efficacious biologics (but no therapeutics), warrants the need for a One Health approach toward detection via improved laboratory-based surveillance, with focal management at the viral source. More effective methods to prevent the spread of rabies from enzootic to free zones are needed.

United Against Rabies Forum: The One Health Concept at Work.

Human deaths from rabies are preventable and can be eliminated by applying a systematic One Health approach. However, this ancient disease still threatens the lives of millions of people in up to 150 countries and kills an estimated 59, 000 people every year. Rabies today is largely a disease of poverty, almost always linked to dog bites, with most deaths occurring in neglected communities in Africa and Asia. The disease places an immense economic burden on its victims, a cost that far outweighs the investment needed to control it. A global framework for rabies elimination in humans is set out in Zero by 30: The Global Strategic Plan to end human deaths from dog-mediated rabies by 2030. Despite the existence of proven control strategies and agreement on the path to eliminating human rabies deaths, mortality numbers from rabies remain high, and COVID-19 has set back efforts even further. But COVID-19 has also highlighted the value of a One Health approach to zoonotic disease and pandemic prevention. Rabies control programs offer a practical route to building One Health capacities that can also address other zoonotic threats, including those with pandemic potential. The United Against Rabies Forum aims to accelerate progress on rabies elimination while applying a One Health approach. The Forum promotes cross-sector collaboration among stakeholders and supports countries in their rabies elimination efforts. Increased political engagement and resource mobilization, both internationally and nationally, will be needed to achieve global rabies goals and can also make One Health implementation a reality.

Neglected Tropical Diseases (NTDs) and COVID-19 Pandemic in Africa: Special Focus on Control Strategies.

Neglected Tropical Diseases (NTDs) are a group of twenty (20) chronic, communicable, infectious diseases endemic to the tropics and sub-tropics climate countries, which are intimately associated with poverty, poor sanitation, limited clean water, and healthcare delivery; and dwellers live in proximity to pathogens and diseases vectors. The pathogens are protozoans, bacteria, helminths, fungi, and viruses. NTDs currently affect about one billion people globally, out of which 500 million are Africans living in rural settlements with low political voice and support. In recent years, NTDs have received little research recognition, development, and funding because more research efforts by global health stakeholders are focused on recognized diseases like cancers, hepatitis, tuberculosis, Acquired Immune-Deficiency Syndrome (AIDS), and malaria that affects most developed countries. The emergence of the viral novel COVID-19 will exacerbate the burden of NTDs on disadvantaged communities as global health efforts are again focused on COVID-19 clearance in terms of research and development to find a drug/vaccine amidst other investigations on recognized infections. This development can result in high death tolls due to NTDs if control measures are not prioritized now. This perspective addresses the need for NTDs control amidst COVID-19 clearance efforts to mitigate another viral health crisis in Africa.

Neglected tropical diseases: impact of COVID-19 and WHO's response - 2021 update

This article is a 2021 update on the WHO report on the impact of COVID-19 on neglected tropical diseases (NTD) and the response appropriated by the WHO. In January 2021, and after almost 2 years of wide-ranging consultations, WHO launched the new NTD roadmap for 2021-2030 that provides a framework and actions to drive progress towards a world free of NTDs, contributing during this decade to the attainment of the United Nations Sustainable Development Goals through: fundamental shifts that put countries, communities and people at the centre of the agenda;supportive cross-sectoral actions, such as health, education, nutrition, water, sanitation, and hygiene and;sustaining and accelerating progress towards the 2030 goals. Furthermore, the roadmap provides opportunities to evaluate, assess, and adjust programmatic actions, as and when needed, over the next decade by setting clear targets and milestones. Another distinct feature of this roadmap is to drive greater ownership by national and local governments, including communities. The overarching 2030 global targets are to: (1) reduce by 90% the number of people requiring interventions against NTDs;(2) have at least 100 countries having eliminated at least one NTD;(3) eradicate 2 diseases (dracunculiasis and yaws) and;(4) reduce by 75% the DALYs related to NTDs. The roadmap will enable future measuring of progress towards eradication, elimination and control of the 20 NTDs by tracking disease-specific targets. Additionally, the roadmap includes 10 cross-cutting targets relevant to progress in the areas of integration, multisectoral coordination, universal health coverage, and country ownership. Examples include a reduction by more than 75% in the number of deaths from vector-borne NTDs such as dengue and leishmaniasis;100% access to basic water supply, sanitation, and hygiene in areas endemic for NTDs;75% integrated treatment coverage index for preventive chemotherapy;90% countries including NTDs in their package of essential services, and 90% countries collecting and reporting NTD data disaggregated by gender.

Potential of Triterpenic Natural Compound Betulinic Acid for Neglected Tropical Diseases New Treatments.

Neglected tropical diseases are one of the most important public health problems in many countries around the world. Among them are leishmaniasis, Chagas disease, and malaria, which contribute to more than 250 million infections worldwide. There is no validated vaccine to prevent these infections and the treatments available are obsolete, highly toxic, and non-effective due to parasitic drug resistance. Additionally, there is a high incidence of these diseases, and they may require hospitalization, which is expensive to the public health systems. Therefore, there is an urgent need to develop new treatments to improve the management of infected people, control the spread of resistant strains, and reduce health costs. Betulinic acid (BA) is a triterpene natural product which has shown antiparasitic activity against Leishmania, Trypanosoma cruzi, and Plasmodium. Here, we review the main results regarding the in vitro and in vivo pharmacological activity of BA and its derivatives against these parasites. Some chemical modifications of BA have been shown to improve its activities against the parasites. Further improvement on studies of drug-derived, as well as structure-activity relationship, are necessary for the development of new betulinic acid-based treatments.

Community Engagement in Cutaneous Leishmaniasis Research in Brazil, Ethiopia, and Sri Lanka: A Decolonial Approach for Global Health.

Cutaneous leishmaniasis (CL) is a parasitic skin disease endemic in at least 88 countries where it presents an urgent, albeit often "neglected" public health problem. In this paper, we discuss our model of decolonial community engagement in the ECLIPSE global health research program, which aims to improve physical and mental health outcomes for people with CL. The ECLIPSE program has four interlinked phases and underpinning each of these phases is sustained and robust community engagement and involvement that guides and informs all activities in ECLIPSE. Our decolonial approach implies that the model for community engagement will be different in Brazil, Ethiopia and Sri Lanka. Indeed, we adopt a critical anthropological approach to engaging with community members and it is precisely this approach we evaluate in this paper. The data and material we draw on were collected through qualitative research methods during community engagement activities. We established 13 Community Advisory Groups (CAGs): in Brazil (n = 4), Ethiopia (n = 6), and Sri Lanka (n = 3). We identified four overarching themes during a thematic analysis of the data set: (1) Establishing community advisory groups, (2) CAG membership and community representation, (3) Culturally appropriate and context-bespoke engagement, and (4) Relationships between researchers and community members. During our first period of ECLIPSE community engagement, we have debunked myths (for instance about communities being "disempowered"), critiqued our own practices (changing approaches in bringing together CAG members) and celebrated successes (notably fruitful online engagement during a challenging COVID-19 pandemic context). Our evaluation revealed a gap between the exemplary community engagement frameworks available in the literature and the messy, everyday reality of working in communities. In the ECLIPSE program, we have translated ideal(istic) principles espoused by such community engagement guidance into the practical realities of "doing engagement" in low-resourced communities. Our community engagement was underpinned by such ideal principles, but adapted to local sociocultural contexts, working within certain funding and regulatory constraints imposed on researchers. We conclude with a set of lessons learned and recommendations for the conduct of decolonial community engagement in global health research.