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General formula for calculating productivity loss. TPC = Total productivity costs (in US$ 2005), NTD = Neglected Tropical Disease, c = Country, y = Year, PS1 = Number of prevalent cases aged 15+ years with sequela 1, PS2 = Number of prevalent cases aged 15+ years with sequela 2, PLs1 = % productivity loss related to sequela 1 of NTD, PLs2 = % productivity loss related to sequela 2 of NTD, I = GDP per capita in the lowest quintile, D = Annual discount rate, t = Time (years beyond 2010). https://doi.org/10.1371/journal.pntd.0006250.g001
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Background
The control or elimination of neglected tropical diseases (NTDs) has targets defined by the WHO for 2020, reinforced by the 2012 London Declaration. We estimated the economic impact to individuals of meeting these targets for human African trypanosomiasis, leprosy, visceral leishmaniasis and Chagas disease, NTDs controlled or eliminated...
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Neglected Tropical Diseases (NTD) represent a serious threat to humans, especially for those living in poor or developing countries. Almost one-sixth of the world population is at risk of suffering from these diseases and many thousands die because of NTDs, to which we should add the sanitary, labor and social issues that hinder the economic develo...
Citations
... Addressing the global problem posed by these Neglected Tropical Diseases (NTD) is a costly, long-term investment, as making a novel drug into the market is a billionaire enterprise [8]. Nevertheless, the socio-economic benefits of improving the CD and HAT scenarios are certain [9]. ...
Chagas disease and Human African Trypanosomiasis, caused by Trypanosoma cruzi and T. brucei, respectively, pose relevant health challenges throughout the world, placing 65 to 70 million people at risk each. Given the limited efficacy and severe side effects associated with current chemotherapy, new drugs are urgently needed for both diseases. Here, we report the screening of the Pathogen Box collection against cruzain and TbrCatL, validated targets for Chagas disease and Human African Trypanosomiasis, respectively. Enzymatic assays were applied to screen 400 compounds, validate hits, determine IC50 values and, when possible, mechanisms of inhibition. In this case, 12 initial hits were obtained and ten were prioritized for follow-up. IC50 values were obtained for six of them (hit rate = 1.5%) and ranged from 0.46 ± 0.03 to 27 ± 3 µM. MMV688246 was found to be a mixed inhibitor of cruzain (Ki = 57 ± 6 µM) while MMV688179 was found to be a competitive inhibitor of cruzain with a nanomolar potency (Ki = 165 ± 63 nM). A putative binding mode for MMV688179 was obtained by docking. The six hits discovered against cruzain and TbrCatL are of great interest for further optimization by the medicinal chemistry community.
... Os países em desenvolvimento precisam lidar com o impacto econômico que afeta a vida das pessoas de diferentes maneiras. A falta de investimento em educação, saneamento e saúde confirma o aumento das doenças (LENK et al., 2018). O Brasil apresentou melhora nas questões socioeconômicas, mas persistem problemas em relação à pobreza, igualdade de gênero e igualdade de acesso à saúde. ...
... Up to 75% of households affected by visceral leishmaniasis in Bangladesh, India, Nepal, and Sudan experience catastrophic costs while seeking diagnosis and treatment, even when tests and medicines are nominally free of charge [33,34,35,36]. Estimates suggest that achieving the WHO roadmap 2020 targets for leprosy and visceral leishmaniasis alone would increase productivity in EMR by nearly $5 billion dollars and avoid out-of-pocket expenses that push individuals further into poverty [37]. ...
Introduction
The 2012–2020 WHO NTD roadmap set targets for control, elimination, and eradication of neglected tropical diseases (NTDs). It recommends 5 strategies, out of which preventive chemotherapy (PC) and intensified disease management were key to achieve targets. WHO estimated that globally, between 2012 and 2019, the number of persons affected by NTDs decreased from nearly 2.1 to 1.7 billion people. We analysed the situation of NTDs in the WHO Eastern Mediterranean Region (EMR) in 2020 to assess the progress with the 2012–2020 roadmap and to identify gaps.
Methods
We reviewed data repositories of national data sources for 2012 to 2019 including the Global Indicator Data Platform for Sustainable Development Goals, the Global Health Observatory data repository, the WHO PC databank, and the EMR data repository. We allocated countries a Red-Amber-Green (RAG) rating based on standardized criteria, on progress and current situation of each of 11 priority NTDs.
Results
All 22 countries in EMR were affected by 1 or more autochthonous or imported NTDs. In 2019, WHO estimated that in EMR, 78 million people required interventions for NTDs, a 38% decline compared with 2012. Twelve of 22 countries needed priority public health action (i.e., red) for 1 or more NTD. Of these, Sudan needed priority public health action for 6 NTDs and Yemen for 5. Eleven countries also needed priority public health action for cutaneous leishmaniasis, and 5 countries for rabies and trachoma. Visceral leishmaniasis is on the increase in Afghanistan, Libya, Syria, and Yemen.
Conclusion
Since the first roadmap of NTDs in 2012, the EMR has made a substantial progress. Nevertheless, many challenges remain in the prevention and control of NTDs. EMR needs a regional approach to control NTDs in countries most affected and a coordinated strategy to stop the continuing increase of cutaneous leishmaniasis and a possible resurgence of visceral leishmaniasis.
... Around 70% of pharmaceutical development is devoted to these disorders. The other is a group of tropical diseases that are often overlooked, called Neglected Tropical Diseases (NTD) (Lenk et al. 2018). There are 17 NTDs, and they affect groups that have minimal visibility and political power. ...
Essential oils are chemical substances composed mainly of terpenes and terpenoids. These compounds are widely investigated due to their lipophilic characteristics and biological and pharmacological properties. Therefore, the objective of this review was to investigate the potential of essential oils against species of the genus Leishmania, parasites causing the infectious disease leishmaniasis. Using the descriptors “Essential oil AND Leishmania” information available in the Scopus© database was collected. 114 articles met the inclusion criteria and were selected for analysis in this study. Among the tests performed, most were of the in vitro type (97.4%) and L. amazonensis (47.4%) and L. infantum (28.9%) were the species most used in these studies. Among the studies that investigated the mechanism of action, the essential oil of the species Tetradenia riparia showed the best result of IC50 (0.03μg/mL) against L. amazonensis isolates. Several works attribute the anti-Leishmania activities of essential oils with different bioactivities, such as: morphological and immunological alterations, antioxidant capacity and enzymatic action. Finally, it is concluded that essential oils have great potential for the development of new drugs against leishmaniasis, however further research is needed through in vivo tests to elucidate the mechanisms of action of such compounds.KeywordsLeishamaniasisTerpenesTerpernoidsMedicinal plantAnthropozoonosisMonoterpenesSesquiterpenes
Lutzomyia
Phlebotomus
Mechanisms of action
... Around 70% of pharmaceutical development is devoted to these disorders. The other is a group of tropical diseases that are often overlooked, called Neglected Tropical Diseases (NTD) (Lenk et al. 2018). There are 17 NTDs, and they affect groups that have minimal visibility and political power. ...
Fungi are organisms that feed from organic matter and act as parasites in living organisms. They are found in different environments and their growth in food products has become a global concern, as well as the resistance to commercial fungicides, due to the economic damage generated by food deterioration and the harmful effects on human health. Thus, the search for new natural fungicides has increased, such as essential oils from plants that have been promising in combating fungi, improving the quantity and quality of foods with low toxicity. This chapter aimed to carry out a bibliographical review on promising essential oils in combating fungal species of the genera Aspergillus, Penicillium, Fusarium, Alternaria, Candida and Cladosporium, the main food spoilage, and their constituents.KeywordsFungiFoodDeteriorationEssential oil
Aspergillus
Penicillium
Fusarium
Alternaria
Candida
Cladosporium
... Around 70% of pharmaceutical development is devoted to these disorders. The other is a group of tropical diseases that are often overlooked, called Neglected Tropical Diseases (NTD) (Lenk et al. 2018). There are 17 NTDs, and they affect groups that have minimal visibility and political power. ...
Awareness about pollution worldwide through the excessive use of chemicals that affect every part of our environment makes the urgent need to use natural alternatives eco-friendly materials to reduce the losses come from synthetic chemicals. In recent decades, a great leap has been made to control weed by synthetic herbicides which are considered the most effective weed control method in comparison with the other methods. Although synthetic herbicides are considered less toxic between other pesticides such as insecticides and fungicides, the usual use, even if it is used at the recommended rates harmed the environment and human health. Previous works indicated that Essential oils have been demonstrated to have good phytotoxic activity on various plant species by suppressing germination and reducing growth parameters. Phytotoxic activity of essential oils can act directly as bioherbicide by effects on one or more than one of the biological processes inside plants which cause the death of plant completely or partially. This chapter highlights the desirable phytotoxic activity of essential oils and their possible uses as natural weed killers.KeywordsAllelopathyEssential oilsPhytotoxic activitySynthetic herbicidesNatural weed killer
... Leishmania donovani (Ld) is the causative agent of visceral leishmaniasis that affects a large portion of the human population in the Indian subcontinent and also in sub-Saharan Africa (Lenk et al, 2018). The apicomplexan parasite has a dual-stage life cycle and lives in the gut of the sandfly vector as promastigotes. ...
Leishmania donovani , the causative agent of visceral leishmaniasis, infects and resides within tissue macrophage cells. It is not clear how the parasite infected cells crosstalk with the noninfected cells to regulate the infection process. During infection, Leishmania adopts a dual strategy for its survival by regulating the intercellular transport of host miRNAs to restrict inflammation. The parasite, by preventing mitochondrial function of host cells, restricts the entry of liver cell derived miR-122–containing extracellular vesicles in infected macrophages to curtail the inflammatory response associated with miR-122 entry. On contrary, the parasite up-regulates the export of miR-146a from the infected macrophages. The miR-146a, associated with the extracellular vesicles released by infected cells, restricts miR-122 production in hepatocytes while polarizing neighbouring naïve macrophages to the M2 state by affecting the cytokine expression. On entering the recipient macrophages, miR-146a dominates the miRNA antagonist RNA-binding protein HuR to inhibit the expression of proinflammatory cytokine mRNAs having HuR-interacting AU-rich elements whereas up-regulates anti-inflammatory IL-10 by exporting the miR-21 to polarize the recipient cells to M2 stage.
... Although control measures and treatments have improved, it remains a priority to produce vaccines against these diseases of poverty. This would be the easiest way to stop their spread and reduce their socioeconomic impact [94]. Vaccination is also the most egalitarian way of protecting the population and solves the problem of people who remain asymptomatic and could act as a reservoir from which new outbreaks could stem [95]. ...
The control of diseases caused by protozoan parasites is one of the United Nations' Sustainable Development Goals. In recent years much research effort has gone into developing a new generation of live attenuated vaccines (LAVs) against malaria, Chagas disease and leishmaniasis. However, there is a bottleneck related to their biosafety, production, and distribution that slows downs further development. The success of irradiated or genetically attenuated sporozoites against malaria, added to the first LAV against leishmaniasis to be evaluated in clinical trials, is indicative that the drawbacks of LAVs are gradually being overcome. However, whether persistence of LAVs is a prerequisite for sustained long-term immunity remains to be clarified, and the procedures necessary for clinical evaluation of vaccine candidates need to be standardized.
... Chagas disease, also known as American trypanosomiasis, is caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), and is one of the 13 most neglected tropical diseases [1][2][3]. The parasite can be transmitted from mother to child, causing congenital CD with potential long-term consequences. ...
Congenital Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is responsible for 22.5% of new cases each year. However, placental transmission occurs in only 5% of infected mothers and it has been proposed that the epithelial turnover of the trophoblast can be considered a local placental defense against the parasite. Thus, Trypanosoma cruzi induces cellular proliferation, differentiation, and apoptotic cell death in the trophoblast, which are regulated, among other mechanisms, by small non-coding RNAs such as microRNAs. On the other hand, ex vivo infection of human placental explants induces a specific microRNA profile that includes microRNAs related to trophoblast differentiation such as miR-512-3p miR-515-5p, codified at the chromosome 19 microRNA cluster. Here we determined the expression validated target genes of miR-512-3p and miR-515-5p, specifically human glial cells missing 1 transcription factor and cellular FLICE-like inhibitory protein, as well as the expression of the main trophoblast differentiation marker human chorionic gonadotrophin during ex vivo infection of human placental explants, and examined how the inhibition or overexpression of both microRNAs affects parasite infection. We conclude that Trypanosoma cruzi-induced trophoblast epithelial turnover, particularly trophoblast differentiation, is at least partially mediated by placenta-specific miR-512-3p and miR-515-5p and that both miRNAs mediate placental susceptibility to ex vivo infection of human placental explants. Knowledge about the role of parasite-modulated microRNAs in the placenta might enable their use as biomarkers, as prognostic and therapeutic tools for congenital Chagas disease in the future.
... The malarial parasite, Plasmodium spp., is a prime example of a protozoan receiving continued funding and scientific interest. However, other protozoan diseases such as Chagas disease and African trypanosomiasis have largely been neglected despite their severe disease profiles [13]. ...
Protozoan parasites are responsible for severe disease and suffering in humans worldwide. Apart from disease transmission via insect vectors and contaminated soil, food, or water, transmission may occur congenitally or by way of blood transfusion and organ transplantation. Several recent outbreaks associated with fresh produce and potable water emphasize the need for vigilance and monitoring of protozoan parasites that cause severe disease in humans globally. Apart from the tropical parasite Plasmodium spp., other protozoa causing debilitating and fatal diseases such as Trypanosoma spp. and Naegleria fowleri need to be studied in more detail. Climate change and socioeconomic issues such as migration continue to be major drivers for the spread of these neglected tropical diseases beyond endemic zones. Due to the complex life cycles of protozoa involving multiple hosts, vectors, and stringent growth conditions, studying these parasites has been challenging. While in vivo models may provide insights into host-parasite interaction, the ethical aspects of laboratory animal use and the challenge of ready availability of parasite life stages underline the need for in vitro models as valid alternatives for culturing and maintaining protozoan parasites. To our knowledge, this review is the first of its kind to highlight available in vitro models for protozoa causing highly infectious diseases. In recent years, several research efforts using new technologies such as 3D organoid and spheroid systems for protozoan parasites have been introduced that provide valuable tools to advance complex culturing models and offer new opportunities toward the advancement of parasite in vitro studies. In vitro models aid scientists and healthcare providers in gaining insights into parasite infection biology, ultimately enabling the use of novel strategies for preventing and treating these diseases.
