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Background Neglected tropical diseases are responsible for considerable morbidity and mortality in low-income populations. International efforts have reduced their global burden, but transmission is persistent and case-finding-based interventions rarely target asymptomatic individuals. Methods We develop a generic mathematical modeling framework for analyzing the dynamics of visceral leishmaniasis in the Indian sub-continent (VL), gambiense sleeping sickness (gHAT), and Chagas disease and use it to assess the possible contribution of asymptomatics who later develop disease (pre-symptomatics) and those who do not (non-symptomatics) to the maintenance of infection. Plausible interventions, including active screening, vector control, and reduced time to detection, are simulated for the three diseases. Results We found that the high asymptomatic contribution to transmission for Chagas and gHAT and the apparently high basic reproductive number of VL may undermine long-term control. However, the ability to treat some asymptomatics for Chagas and gHAT should make them more controllable, albeit over relatively long time periods due to the slow dynamics of these diseases. For VL, the toxicity of available therapeutics means the asymptomatic population cannot currently be treated, but combining treatment of symptomatics and vector control could yield a quick reduction in transmission. Conclusions Despite the uncertainty in natural history, it appears there is already a relatively good toolbox of interventions to eliminate gHAT, and it is likely that Chagas will need improvements to diagnostics and their use to better target pre-symptomatics. The situation for VL is less clear, and model predictions could be improved by additional empirical data. However, interventions may have to improve to successfully eliminate this disease. [ABSTRACT FROM AUTHOR]

Background: In the Americas, the Pan American Health Organization (PAHO) has promoted initiatives that aim at the elimination of mother-to-child transmitted diseases for over two decades. Although Guatemala has assumed the commitment to improve access and coverage of reproductive and perinatal services, the goals have not yet been reached. Often, the implementation of these efforts is hampered by complexities rooted in social, cultural, and environmental intersections. The objective of this work is to share our experience applying gender intersectionality as a methodological and analytical tool in a participatory research project that aims to improve access to maternal and child health screening services. The study shows the novel strategy that incorporates intersectionality contributing to evidence on how it can be applied to strengthen public health efforts around the implementation of the EMTCT Plus (Elimination of mother-to-child transmission of HIV, Syphilis, Hepatitis B, and Chagas disease) framework, in the mostly rural municipality of Comapa, in Guatemala. Methods: We applied a participatory methodology, integrating theoretical and methodological frameworks to have an intersectional understanding of health services delivered by both, midwives, and the public health institution, for the prevention, diagnosis, treatment, and follow-up of HIV, Syphilis, Hepatitis B, and Chagas. The data was collected by conducting interviews, focus groups, workshops, and reviewing laboratory databases, guided by five strategies from a cultural appropriateness framework. Results: The intersectional analysis shed light on the synergies and gaps of the current efforts and protocols implemented by both the midwives and the Ministry of Health. The services offered for the four diseases were often delivered independently from each other, and a comprehensive educational and communication material strategy was absent. However, our findings will be used to inform consistent, locally relevant, and culturally appropriate educational content for the local population, also following the national policy guidelines. Conclusions: Using intersectionality as a method and as an analytical tool allowed us to understand the (1) interrelation of diverse social, cultural, and environmental determinants which influence the delivery of health services, as well as (2) the dynamics between the traditional and institutional health systems. (3) Community engagement and the participation of different stakeholders in a consultative process have been fundamental for the conceptual and methodological tenets of this research. (4) Finally, giving a more prominent role to midwives can strengthen sustainability and cultural appropriateness, which is complementary to the delivery of institutional health services. [ABSTRACT FROM AUTHOR]

Trypanosomiasis is an important but neglected tropical diseases which continues to cause morbidity and mortality on a large scale in sub-Saharan Africa. In the present study, the aqueous leaf extract, flavonoid fraction, and subfractions of the flavonoid from A. senegalensis leaves were evaluated for their antitrypanosomal activities, effects on some hematological parameters, and some liver-based enzymes in mice infected with Trypanosoma brucei brucei. Mice treated with aqueous extract at a concentration range of 100–400 mg kg bw exhibited parasite inhibition range between 66.08 and 73.09% while mice treated with the flavonoid fraction (50-200 mg/kg bw) exhibited higher parasite inhibition (83.37-86.38%). Mice treated with subfractions of the flavonoids showed a significant decrease in parasite count (p < 0.05), with subfraction 3 completely clearing parasites in the circulation after twenty-one days of treatment. Biochemical analysis revealed that the subfraction 3 restored the alterations in the serum aspartate transaminase (AST), alanine transaminase (ALT), and total protein concentrations that were observed in the infected nontreated mice. The subfraction 3 was subsequently characterized by HPLC analysis which revealed the presence of rutin (RT: 22.26, 65.34 ppm) as the most abundant bioactive compound that could be attributed to the bioactivity of the subfraction 3. Other polyphenolic compounds identified included gallic acid (RT: 4.39, 0.578 ppm), quercetin (RT: 37.27, 0.729 ppm), kaempferol (RT: 38.33, 1.52 ppm), and luteolin (RT; 39.173, 32.77 ppm). Taken together, subfraction 3 of the flavonoid fraction from of A. senegalensis demonstrated potent antitrypanosomal activities and therefore represents a reserve of bioactive metabolite worthy of further exploration for the treatment of trypanosomiasis. [ABSTRACT FROM AUTHOR]

Trypanosomosis is responsible for the death of 3 million heads of cattle yearly, with 50 million animals at risk in sub-Saharan Africa. The problem of trypanosomosis is still far from being solved due to the fact that trypanosomes affect multiple hosts, widespread trypanocidal drug resistance and antigenic variation displayed by trypanosomes. Trypanocidal drugs: Isometamidium chloride (ISM) and Diminazene aceturate (DA) are the most widely used drugs for control animal trypanosomosis in Ethiopia. However, there is growing concern that their future effectiveness may be severely reduced by widespread drug resistance. Because it is very unlikely that new trypanosomal drugs will be released on to the market in the future, it is essential to maintain the efficacy of the currently available drugs. So proper detection methods of drug resistance by test in ruminants, in mice, in vitro, molecular tests and xenodiagnoses and followed by the right techniques on the delay of the development of drug resistance like reduction in the number of treatments, avoidance of under dosage, change of drugs, use of national drug police and if once resistance present allowing integrated control measures such as reducing vector numbers to reduce the number of drug treatments was great importance. [ABSTRACT FROM AUTHOR]

The article offers news briefs related to public health around the world as of August 2024. Topics mentioned include the increase in physical inactivity among adults by 31 percent, the release of a health alert by World Health Organization (WHO) regarding falsified semaglutide used for regulating the levels of blood sugar, and the death rate pear year due to alcohol consumption.

Incentives are a useful tool in encouraging healthy behavior as part of public health initiatives. However, there remains concern about motivation crowd out—a decline in levels of motivation to undertake a behavior to below baseline levels after incentives have been removed—and few public health studies have assessed for motivation crowd out. Here, we assess the feasibility of identifying motivation crowd out following a lottery to promote participation in a Chagas disease vector control campaign. We look for evidence of crowd out in subsequent participation in the same behavior, a related behavior, and an unrelated behavior. We identified potential motivation crowd out for the same behavior, but not for related behavior or unrelated behaviors after lottery incentives are removed. Despite some limitations, we conclude that motivation crowd out is feasible to assess in large-scale trials of incentives. [ABSTRACT FROM AUTHOR]

Human African trypanosomiasis (HAT) is considered a highly promising candidate for elimination within the next decade. This paper argues that the experiential knowledge of frontline health workers will be critical to achieve this goal. Interviews are used to explore the ways in which HAT workers understand, maintain, and adjust their skills amidst global and national challenges. We contrast two cases: South Sudan where HAT expertise is scattered and has been repeatedly rebuilt, and the Democratic Republic of Congo (DRC) where specialised mobile detection teams have pro-actively tested people at risk for almost a century. We describe HAT careers where skills are built through participation in HAT technology trials and screening programmes; in the DRC expertise is also supported through formal rotations in screening teams and HAT referral centres for new health workers. As cases fade, de-skilling is a real threat as awareness of populations and authorities diminishes and previously vertical programmes evolve, re-configuring professional development and career paths and associated opportunities for HAT practice. To avoid repeating the mistakes of the 1960s, when elimination also seemed close at hand, we need to recognise that the 'last mile' of elimination hinges on protecting the fragile expertise of frontline health workers. [ABSTRACT FROM AUTHOR]

Although Chagas disease only infects children in the American hemisphere, and though children do not suffer the morbidity and mortality of the disease, it is a disease of children. The acute form of the infection, though self-limited, is a harbinger of the most common cause of heart failure in the world. The treatment has moderate benefit and thus, identifying the infection in children and preventing the disease has a profound impact on the goal of reducing some of the millions of deaths from heart failure [ABSTRACT FROM AUTHOR]

Background: Gambiense human African trypanosomiasis ([gHAT] sleeping sickness) is a vector-borne disease that is typically fatal without treatment. Intensified, mainly medical-based, interventions in endemic areas have reduced the occurrence of gHAT to historically low levels. However, persistent regions, primarily in the Democratic Republic of Congo (DRC), remain a challenge to achieving the World Health Organization's goal of global elimination of transmission (EOT).Methods: We used stochastic models of gHAT transmission fitted to DRC case data and explored patterns of regional reporting and extinction. The time to EOT at a health zone scale (~100 000 people) and how an absence of reported cases informs about EOT was quantified.Results: Regional epidemiology and level of active screening (AS) both influenced the predicted time to EOT. Different AS cessation criteria had similar expected infection dynamics, and recrudescence of infection was unlikely. However, whether EOT has been achieved when AS ends is critically dependent on the stopping criteria. Two or three consecutive years of no detected cases provided greater confidence of EOT compared with a single year (~66%-75% and ~82%-84% probability of EOT, respectively, compared with 31%-51%).Conclusions: Multiple years of AS without case detections is a valuable measure to assess the likelihood that the EOT target has been met locally. [ABSTRACT FROM AUTHOR]

An introduction to articles published within the issue is presented on topics including inter-imperial collaboration in agriculture in early 20th-century Hawaii, perspective of geology and state power, and effort to combat trypanosomiasis or sleeping sickness in German and British colonies.

As sleeping sickness appeared in epidemics across Africa c. 1900, it stimulated a race among colonial medical personnel and Europe-based scientists to discover its causative pathogen, its mode of transmission, and, ideally, a cure. Scientists circulated between hubs of research in Europe and key field sites in Africa, monitoring each other's progress and often maintaining long-term relationships colored by collaboration and competition. The Lake Victoria littoral was an epicenter of both significant mortality and important research before WWI. This article explores the intellectual implications of colonial connectivity at local scale, focusing on changing ideas about sleeping sickness, the communication of research strategies and methods, and the circumstances of life and research in this imperial hinterland and colonial borderland in eastern Africa. Exploring research dynamics around Lake Victoria illuminates the inadequacies of colonial scientific and medical capabilities and both the generative and limiting aspects that the contingencies of colonial research created. [ABSTRACT FROM AUTHOR]

Background. The World Health Organization's 2020 goals for Chagas disease are (1) interrupting vector-borne intradomiciliary transmission and (2) having all infected people under care in endemic countries. Insecticide spraying has proved efficacious for reaching the first goal, but active transmission remains in several regions. For the second, treatment has mostly been restricted to recently infected patients, who comprise only a small proportion of all infected individuals. Methods. We extended our previous dynamic transmission model to simulate a domestic Chagas disease transmission cycle and examined the effects of both vector control and etiological treatment on achieving the operational criterion proposed by the Pan American Health Organization for intradomiciliary, vectorial transmission interruption (ie, <2% seroprevalence in children <5 years of age). Results. Depending on endemicity, an antivectorial intervention that decreases vector density by 90% annually would achieve the transmission interruption criterion in 2-3 years (low endemicity) to >30 years (high endemicity). When this strategy is combined with annual etiological treatment in 10% of the infected human population, the seroprevalence criterion would be achieved, respectively, in 1 and 11 years. Conclusions. Combining highly effective vector control with etiological (trypanocidal) treatment in humans would substantially reduce time to transmission interruption as well as infection incidence and prevalence. However, the success of vector control may depend on prevailing vector species. It will be crucial to improve the coverage of screening programs, the performance of diagnostic tests, the proportion of people treated, and the efficacy of trypanocidal drugs. While screening and access can be incremented as part of strengthening the health systems response, improving diagnostics performance and drug efficacy will require further research. [ABSTRACT FROM AUTHOR]

Background. Control of gambiense sleeping sickness relies predominantly on passive and active screening of people, followed by treatment. Methods. Mathematical modeling explores the potential of 3 complementary interventions in high- and low-transmission settings. Results. Intervention strategies that included vector control are predicted to halt transmission most quickly. Targeted active screening, with better and more focused coverage, and enhanced passive surveillance, with improved access to diagnosis and treatment, are both estimated to avert many new infections but, when used alone, are unlikely to halt transmission before 2030 in highrisk settings. Conclusions. There was general model consensus in the ranking of the 3 complementary interventions studied, although with discrepancies between the quantitative predictions due to differing epidemiological assumptions within the models. While these predictions provide generic insights into improving control, the most effective strategy in any situation depends on the specific epidemiology in the region and the associated costs. [ABSTRACT FROM AUTHOR]

Background: Trypanosoma cruzi (T. cruzi) infects millions of Latin Americans each year and can induce chagasic megacolon. Little is known about how serotonin (5-HT) modulates this condition. Aim We investigated whether 5-HT synthesis alters T. cruzi infection in the colon.Materials and Methods: Forty-eight paraffin-embedded samples from normal colon and chagasic megacolon were histopathologically analyzed (173/2009). Tryptophan hydroxylase 1 (Tph1) knockout (KO) mice and c-KitW-sh mice underwent T. cruzi infection together with their wild-type counterparts. Also, mice underwent different drug treatments (16.1.1064.60.3).Results: In both humans and experimental mouse models, the serotonergic system was activated by T. cruzi infection (p < 0.05). While treating Tph1KO mice with 5-HT did not significantly increase parasitemia in the colon (p > 0.05), rescuing its synthesis promoted trypanosomiasis (p < 0.01). T. cruzi-related 5-HT release (p < 0.05) seemed not only to increase inflammatory signaling, but also to enlarge the pericryptal macrophage and mast cell populations (p < 0.01). Knocking out mast cells reduced trypanosomiasis (p < 0.01), although it did not further alter the neuroendocrine cell number and Tph1 expression (p > 0.05). Further experimentation revealed that pharmacologically inhibiting mast cell activity reduced colonic infection (p < 0.01). A similar finding was achieved when 5-HT synthesis was blocked in c-KitW-sh mice (p > 0.05). However, inhibiting mast cell activity in Tph1KO mice increased colonic trypanosomiasis (p < 0.01).Conclusion: We show that mast cells may modulate the T. cruzi-related increase of 5-HT synthesis in the intestinal colon. [ABSTRACT FROM AUTHOR]

In previous studies the aerial parts of Achillea fragrantissima were found to have substantial antileishmanial and antitrypanosomal activity. A bioassay-guided fractionation of a dichloromethane extract yielded the isolation of the essential anti-trypanosomal compounds of the plant. Seven sesquiterpene lactones (including Achillolide-A), two flavonoids, chrysosplenol-D and chrysosplenetine, and four alkamides (including pellitorine) were identified. This is the first report for the isolation of the sesquiterpene lactones 3 and 4 , chrysosplenetine and the group of alkamides from this plant. Bioevaluation against Trypanosoma brucei brucei TC221 (T.b brucei) using the Alamar-Blue assay revealed the novel alkamide 13 to have an IC 50 value of 40.37 μM. A compound library, derived from the alkamide pellitorine ( 10 ), was synthesized and bioevaluated in order to find even more active substances. The most active compounds 26 and 27 showed activities in submicromolar concentrations and selectivity indices of 20.1 and 45.6, respectively, towards macrophage cell line J774.1 . Toxicity of 26 and 27 was assessed using the greater wax moth Galleria mellonella larvae as an in vivo model. No significant toxicity was observed for the concentration range of 1.25–20 mM. [ABSTRACT FROM AUTHOR]

Baccharis retusa, a medicinal Brazilian plant from Asteraceae, has been used in Brazilian folk medicine to treatment of several illnesses, including parasitic diseases. Bioactivity-guided fractionation of the n-hexane extract from the aerial parts of B. retusa resulted in the isolation and characterization of three active related diterpenes: ent -15β-senecioyl-oxy-kaur-16-en-19-oic acid ( 1 ), ent -kaur-16-en-19-oic ( 2 ) and ent -16-oxo-17-nor-kauran-19-oic ( 3 ) acids. The structures of isolated compounds were defined by spectroscopic analysis, including NMR and HRESIMS. Antitrypanosomal activity of 1–3 was performed against cell-derived trypomastigotes using the colorimetric resazurin assay. The obtained results demonstrated that isolated compounds displayed a reduced toxicity against NCTC cells and were effective against the trypomastigote forms of T. cruzi with IC 50 values of 3.8 μM ( 1 ), 75.3 μM ( 2 ) and 44.2 μM ( 3 ). Additionally, compound 3 displayed activity against amastigote forms of T. cruzi with IC 50 of 83.2 μM. Compound 1 displayed the highest selectivity index (SI) when considered the trypomastigote forms, and its effect in the plasma membrane of parasite was evaluated using the fluorescent probe SYTOX Green. A considerable permeabilization (57%) in the membrane of the parasite was observed when compared to the untreated trypomastigotes. These data demonstrate, for the first time, the antitrypanosomal activity and mechanism of action of 1 and related compounds 2 and 3 , obtained from aerial parts of B. retusa . [ABSTRACT FROM AUTHOR]

The establishment of the Pan-African Tsetse and Trypanosomosis Eradication Campaign (PATTEC) falling under the African Union Commission, and the initiation of national PATTEC projects in affected African countries stimulated a revival of national and sub-regional efforts and helped to generate donor support for creating sustainable agricultural and livestock development zones that are free of tsetse and trypanosomosis (T&T). Such projects are long-term, complex undertakings, requiring careful planning and consideration of relevant technical and non-technical interdependencies. There is international consensus that T&T interventions should: (a) adopt a phased and conditional approach in their planning, implementation, and monitoring; (b) adhere to the integrated pest management area-wide (AW-IPM) concept, ensuring that the most appropriate combination or sequence of intervention measures is selected; and (c) follow the AW-IPM concept of targeting entire isolated or well-confined insect pest populations. The phases of this process include: (a) policy and strategy development, assurance of long-term commitment, and establishment of effective management structures; (b) baseline data collection; (c) general technical feasibility assessment; (d) consideration of various relevant factors and trends; (e) detailed assessment of the technical feasibility of combinations of intervention tactics that may or may not include a sterile insect technique component; (f) capacity development and pre-operational work; (g) operational implementation of an AW-IPM campaign to create T&T-free zones; and (h) adherence to agreed procedures for the ‘Declaration of Assumption of Freedom from T&T’, and, eventually, the ‘Declaration of Elimination’. This paper provides guidance on the steps to be followed to assess the feasibility of creating T&T-free zones. [ABSTRACT FROM PUBLISHER]

Tithonia diversifolia (Asteraceae), is used as traditional medicine in tropical countries for the treatment of various diseases, including malaria. Although numerous studies have assessed the antimalarial properties, nothing is known about the effect of T. diversifolia extracts on trypanosomiasis. In this study extracts of T. diversifolia aerial parts were evaluated for their bioactivity against Trypanosoma brucei. The activity was studied against bloodstream forms of T. brucei (TC221), as well as against mammalian cells (BALB/3T3 mouse fibroblasts), as a counter-screen for toxicity. Both methanolic and aqueous extracts showed significant effects with IC 50 values of 1.1 and 2.2 μg/mL against T. brucei (TC221) and 5.2 and 3.7 μg/mL against BALB/3T3 cells, respectively. A bioassay-guided fractionation on the methanolic extract yielded in identification of active fractions (F8 and F9) with IC 50 values of 0.41 and 0.43 μg/mL, respectively, against T. brucei (TC221) and 1.4 and 1.5 μg/mL, respectively, against BALB/3T3 cells,. The phytochemical composition of the extracts and the purified fractions were investigated using HPLC-ESI-MS/MS and 1D and 2D NMR spectra showing the presence of sesquiterpene lactones that in turn were subjected to the isolation procedure. Tagitinin A and C were rather active but the latter presented a very strong inhibition on T. brucei (TC221) with an IC 50 value of 0.0042 μg/mL. This activity was 4.5 times better than that of the reference drug suramin. The results of this study shed light on the antitrypanosomal effects of T. diversifolia extracts and highlighted tagitinin C as one of the possible responsible for this effect. Further structure activity relationships studies on tagitinins are needed to consider this sesquiterpenes as lead compounds for the development of new antitrypanosomal drugs. [ABSTRACT FROM AUTHOR]

Current low participation rates in vector control programmes in Arequipa, Peru complicate the control of Chagas disease. Using focus groups (n = 17 participants) and semi-structured interviews (n = 71) conducted in March and May 2013, respectively, we examined barriers to and motivators of household participation in an indoor residual spray (IRS) campaign that had taken place one year prior in Arequipa. The most common reported barriers to participation were inconvenient spray times due to work obligations, not considering the campaign to be necessary, concerns about secondary health impacts (e.g. allergic reactions to insecticides), and difficulties preparing the home for spraying (e.g. moving heavy furniture). There was also a low perception of risk for contracting Chagas disease that might affect participation. The main motivator to participate was to ensure personal health and well-being. Future IRS campaigns should incorporate more flexible hours, including weekends; provide appropriate educational messages to counter concerns about secondary health effects; incorporate peer educators to increase perceived risk to Chagas in community; obtain support from community members and leaders to build community trust and support for the campaign; and assist individuals in preparing their homes. Enhancing community trust in both the need for the campaign and its operations is key. [ABSTRACT FROM PUBLISHER]

The synthesis of four cymantrene-5-fluorouracil derivatives (1-4) and two cymantrene-adenine derivatives (5 and 6) is reported. All of the compounds were characterized by spectroscopic methods and the crystal structure of two derivatives (1 and 6), together with the previously described cymantrene-adenine compound C was determined by X-ray crystallography. While the compounds 1 and 6 crystallized in the triclinic P-1 space group, compound C crystallized in the monoclinic P21/m space group. The newly synthesized compounds 1-6 were tested together with the two previously described cymantrene derivatives B and C for their in vitro antiproliferative activity against seven cancer cell lines (MCF-7, MCF-7/DX, MDA-MB-231, SKOV-3, A549, HepG2m and U-87-MG), five bacterial strains Staphylococcus aureus (methicillin-sensitive, methicillin-resistant and vancomycin-intermediate strains), Staphylococcus epidermidis, and Escherichia coli, including clinical isolates of S. aureus and S. epidermidis, as well as against the protozoan parasite Trypanosoma brucei. The most cytotoxic compounds were derivatives 2 and C for A549 and SKOV-3 cancer cell lines, respectively, with 50% growth inhibition (IC50) values of about 7 μM. The anticancer activity of the cymantrene compounds was determined to be due to their ability to induce oxidative stress and to trigger apoptosis and autophagy in cancer cells. Three derivatives (1, 4 and 5) displayed promising antitrypanosomal activity, with GI50 values in the low micromolar range (3-4 μM). The introduction of the 5-fluorouracil moiety in 1 enhanced the trypanocidal activity when compared to the activity previously reported for the corresponding uracil derivative. The antibacterial activity of cymantrene compounds 1 and C was within the range of 8-64 μg/mL and seemed to be the result of induced cell shrinking. [ABSTRACT FROM AUTHOR]

Quinone-based compounds have been exploited to treat infectious diseases and cancer, with such chemicals often functioning as inhibitors of key metabolic pathways or as prodrugs. Here, we screened an aziridinyl 1,4-benzoquinone (ABQ) library against the causative agents of trypanosomiasis, and cutaneous leishmaniasis, identifying several potent structures that exhibited EC50 values of <100 nM. However, these compounds also displayed significant toxicity towards mammalian cells indicating that they are not suitable therapies for systemic infections. Using anti- T. brucei ABQs as chemical probes, we demonstrated that these exhibit different trypanocidal modes of action. Many functioned as type I nitroreductase (TbNTR) or cytochrome P450 reductase (TbCPR) dependent prodrugs that, following activation, generate metabolites which promote DNA damage, specifically interstrand crosslinks (ICLs). Trypanosomes lacking TbSNM1, a nuclease that specifically repairs ICLs, are hypersensitive to most ABQ prodrugs, a phenotype exacerbated in cells also engineered to express elevated levels of TbNTR or TbCPR. In contrast, ABQs that contain substituent groups on the biologically active aziridine do not function as TbNTR or TbCPR-activated prodrugs and do not promote DNA damage. By unravelling how ABQs mediate their activities, features that facilitate the desired anti-parasitic growth inhibitory effects could be incorporated into new, safer compounds targeting these neglected tropical diseases. [ABSTRACT FROM AUTHOR]

Background: The parasitic Chagas disease is caused by the protozoan Trypanosoma cruzi, which is mainly transmitted by insect vectors. Other infection routes, both in endemic and in nonendemic areas, include organ and marrow transplantation, congenital transmission, and blood transfusion. Asymptomatic chronic chagasic individuals may have a low and transient parasitemia in peripheral blood and, consequently, they can unknowingly transmit the disease via blood transfusion. Riboflavin and ultraviolet (UV) light pathogen reduction is a method to reduce pathogen transfusion transmission risk based on damage to the pathogen nucleic acids.Study Design and Methods: In this study, we tested the effectiveness of this technology for the elimination of T. cruzi parasites in artificially contaminated whole blood units (WBUs) and thus for decreasing the risk of T. cruzi transfusion transmission. The contaminated WBUs were leukoreduced by filtration and treated with riboflavin and UV light. The level of pathogen reduction was quantified by a real-time polymerase chain reaction (qPCR) and a real-time reverse transcription-polymerase chain reaction (RT-qPCR) as a viability assay.Results: The RNA (cDNA) quantification of the parasites showed a more than 99% reduction of viable T. cruzi parasites after leukoreduction and a complete reduction (100%) after the riboflavin and UV light treatment.Conclusion: Riboflavin and UV light treatment and leukoreduction used in conjunction appears to eliminate significant amounts of viable T. cruzi in whole blood. Both strategies could complement other blood bank measures already implemented to prevent the transmission of T. cruzi via blood transfusion. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO) has targeted the elimination of Human African trypanosomiasis (HAT) ‘as a public health problem’ by 2020. The selected indicators of elimination should be monitored every two years, and we provide here a comprehensive update to 2014. The monitoring system is underpinned by the Atlas of HAT. Results: With 3,797 reported cases in 2014, the corresponding milestone (5,000 cases) was surpassed, and the 2020 global target of ‘fewer than 2,000 reported cases per year’ seems within reach. The areas where HAT is still a public health problem (i.e. > 1 HAT reported case per 10,000 people per year) have halved in less than a decade, and in 2014 they corresponded to 350 thousand km2. The number and potential coverage of fixed health facilities offering diagnosis and treatment for HAT has expanded, and approximately 1,000 are now operating in 23 endemic countries. The observed trends are supported by sustained surveillance and improved reporting. Discussion: HAT elimination appears to be on track. For gambiense HAT, still accounting for the vast majority of reported cases, progress continues unabated in a context of sustained intensity of screening activities. For rhodesiense HAT, a slow-down was observed in the last few years. Looking beyond the 2020 target, innovative tools and approaches will be increasingly needed. Coordination, through the WHO network for HAT elimination, will remain crucial to overcome the foreseeable and unforeseeable challenges that an elimination process will inevitably pose. [ABSTRACT FROM AUTHOR]

Background: We evaluated the effectiveness of treating women of childbearing age with benznidazole to prevent congenital Chagas disease (CCD), as well as the usefulness of polymerase chain reaction (PCR) as a tool to predict the risk of transmission.Methods: Prospective study involving 144 T. cruzi seropositive pregnant women. The parasitological status was studied by PCR in 159 pregnancies, 38 of which involved a cohort of previously treated mothers. One hundred sixty children were examined by PCR and serologically studied at 0-6, 9 and 12 months and annually after treatment.Results: PCR was seen to be useful for predicting the risk of congenital transmission: 18.8% of mothers with a positive PCR result transmitted the infection (16 infected children out of 85 pregnancies). No infected infants were detected among 74 pregnancies when PCR was negative. Of the treated mothers, 92.1% had negative PCR results, compared with 32.2% of untreated mothers. No infected infants were detected from previously treated mothers, compared with 13.2% among untreated mothers (P = .019; χ2). All infants treated before the first year of life were cured.Conclusions: Treating infected women of childbearing age prevents congenital Chagas disease. Polymerase chain reaction screening of T. cruzi-infected pregnant women is a useful tool for predicting the risk of congenital transmission. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Leaves from the plant species studied herein are traditionally used in northern Nigeria against various protozoan infections. However, none of these herbal preparations have been standardized, nor have their toxicity to mammalian cells been investigated. In search of improved and non-toxic active antiprotozoal principles that are not cross-resistant with current anti-parasitics, we here report the results of the in vitro screening of extracts from seven selected medicinal plant species ( Centrosema pubescens , Moringa oleifera , Tridax procumbens , Polyalthia longifolia , Newbouldia laevis, Eucalyptus maculate , Jathropha tanjorensis ), used traditionally to treat kinetoplastid infections in Nigeria, and the isolation of their bioactive principles. Aim of the study To investigate the efficacies of medicinal plant extracts, and of compounds isolated therefrom, against kinetoplastid parasites, assess cross-resistance to existing chemotherapy, and assay their toxicity against mammalian cells in vitro. Material and methods Plants were extracted with hexane, ethyl acetate and methanol. Active principles were isolated by bioassay-led fractionation, testing for trypanocidal activity, and identified using NMR and mass spectrometry. EC 50 values for their activity against wild-type and multi-drug resistant Trypanosoma brucei were obtained using the viability indicator dye resazurin. Results Seven medicinal plants were evaluated for activity against selected kinetoplastid parasites. The result shows that crude extracts and isolated active compounds from Polyalthia longifolia and Eucalyptus maculata , in particular, display promising activity against drug-sensitive and multi-drug resistant Trypanosoma brucei . The EC 50 value of a clerodane (16α-hydroxy-cleroda-3,13(14)-Z-dien-15,16-olide) isolated from Polyalthia longifolia was as low as 0.38 µg/mL, while a triterpenoid (3β,13β-dihydroxy-urs-11-en-28-oic acid) isolated from Eucalyptus maculata displayed an EC 50 of 1.58 µg/mL. None of the isolated compounds displayed toxicity towards Human Embryonic Kidney cells at concentrations up to 400 µg/mL. In addition, the isolated compounds were active against Leishmania mexicana , as well as against T. congolense . Conclusion We have isolated a clerodane compound from Polyalthia longifolia that shows low toxicity, no cross-resistance with current treatments, and promising activity against both human-infective and veterinary Trypanosoma species. [ABSTRACT FROM AUTHOR]

In spite of numerous reports of avian Trypanosoma spp. in birds throughout the world, patterns of the distribution and prevalence of these blood parasites remains insufficiently understood. It is clear that spatial heterogeneity influences parameters of parasite distributions in natural populations, but data regarding avian trypanosomes are scarce. Using microscopy and molecular diagnostic methods, we analysed the variation of prevalence of avian Trypanosoma parasites in two widespread African bird species, the yellow-whiskered greenbul Andropadus latirostris and the olive sunbird Cyanomitra olivacea . In all, 353 birds were captured in pristine forests and agroforest sites in Cameroon and Ghana. Overall, the prevalence of avian trypanosomes was 51.3%. Five morphospecies were reported ( Trypanosoma everetti , T. anguiformis , T. avium , T. naviformis , T. ontarioensis ). Trypanosoma everetti predominated, representing 98% of all Trypanosoma spp. reports, and it was present in both avian hosts. The prevalence of T. everetti was significantly less in the yellow-whiskered greenbul (19%) than olive sunbird (83%), and the same pattern of prevalence was reported in these avian hosts at different study sites. We found no interaction between sites and the prevalence of T. everetti . For both avian hosts, the prevalence did not differ significantly between pristine forests and agroforests. This indicates the same pattern of transmission at sites with different levels of deforestation and suggests that spatial heterogeneity related to deforestation does not affect the prevalence of avian Trypanosoma infections. It is likely that host-related factors, but not environmental conditions favour or reduce these parasite infections in forests of sub-Saharan Africa. Microscopic and PCR-based diagnostics showed the same sensitivity in diagnostics of T. everetti . We discuss the implications of these findings for the epidemiology of avian trypanosomiasis in natural populations. [ABSTRACT FROM AUTHOR]

Efforts to control neglected tropical diseases have increasingly focused on questions of implementation. But how should we conceptualize the implementation process? Drawing on ethnographic fieldwork between 2010 and 2012, in this article I explore efforts by a small-scale public–private partnership to use private veterinarians to sustainably control zoonotic sleeping sickness in Uganda. With a fundamental tension between business incentives and vector control, I show how divergences in knowledge, power, values, and social norms shaped project implementation and community responses. Reflecting more widely on the relationships between project plans and local realities, I argue that these encounters reveal the heuristic value in approaching global health interventions as evolving ‘social experiments.’ This metaphor reveals the uncertainty inherent to dominant narratives and models, the role of available expertise in defining the limits of action, and the need for continuous adaption to synchronize with emergent social and institutional topographies. [ABSTRACT FROM PUBLISHER]

Chagas disease, leishmaniasis, onchocerciasis and lymphatic filariasis are all vectorborne neglected tropical diseases (NTDs) that are responsible for significant disease burden in impoverished children and adults worldwide. As vectorborne parasitic diseases, they can all be targeted for elimination through vector control strategies. Examples of successful vector control programmes for these diseases over the past two decades have included the Southern Cone Initiative against Chagas disease, the Kala-azar Control Scheme against leishmaniasis, the Onchocerciasis Control Programme and the lymphatic filariasis control programme in The Gambia. A common vector control component in all of these programmes is the use of adulticides including dichlorodiphenyltrichloroethane and newer synthetic pyrethroid insecticides against the insect vectors of disease. Household spraying has been used against Chagas disease and leishmaniasis, and insecticide-treated bed nets have helped prevent leishmaniasis and lymphatic filariasis. Recent trends in vector control focus on collaborations between programmes and sectors to achieve integrated vector management that addresses the holistic vector control needs of a community rather than approaching it on a disease-by-disease basis, with the goals of increased efficacy, sustainability and cost-effectiveness. As evidence of vector resistance to currently used insecticide regimens emerges, research to develop new and improved insecticides and novel control strategies will be critical in reducing disease burden. In the quest to eliminate these vectorborne NTDs, efforts need to be made to continue existing control programmes, further implement integrated vector control strategies and stimulate research into new insecticides and control methods. [ABSTRACT FROM AUTHOR]

Background: Human African Trypanosomiasis (HAT) is a protozoan parasitic disease caused by Trypanosoma brucei. The disease is endemic in regions of sub-Saharan Africa, covering 36 countries and more than 60 million people at the risk. Only few drugs are available for the treatment of HAT. Current drugs suffer from severe toxicities and require intramuscular or intravenous administrations. The situation is further aggravated due to the emergence of drug resistance. There is an urgent need of new drugs that are effective orally against both stages of HAT. Natural products offer an unmatched source for bioactive molecules with new chemotypes. Methods: The extracts prepared from 522 plants collected from various parts of the North America were screened in vitro against blood stage trypamastigote forms of T. brucei. Active extracts were further screened at concentrations ranging from 10 to 0.4 µg/mL Active extracts were also investigated for toxicity in Differentiated THP1 cells at 10 µg/mL concentration. The results were computed for dose-response analysis and determination of IC50/IC90 values. Results: A significant number (150) of extracts showed >90 % inhibition of growth of trypomastigote blood forms of I brucei in primary screening at 20 µg/mL concentration. The active extracts were further investigated for dose-response inhibition of T. brucei growth. The antitrypansomal activity of 125 plant extracts was confirmed with IC50 < 10 µg/mL None of these active extracts showed toxicity against differentiated THP1 cells. Eight plants extracts namely, Alnus rubra, Hoita macrostachya, Sabal minor, Syzygium aqueum, Hamamelis virginiana, Coccoloba pubescens, Rhus integrifolia and Nuphar luteum were identified as highly potent antitrypanosomal extracts with IC50 values <1 µg/mL Conclusions: Limited phytochemical and pharmacological reports are available for the lead plant extracts with potent antitrypanosomal activity. Follow up evaluation of these plant extracts is likely to yield new antitrypanosomal drug-leads or alternate medicines for treatment of HAT. [ABSTRACT FROM AUTHOR]

The article discusses the strategy to control sleeping sickness or Human African Trypanosomiasis (HAT), which in Africa is caused by T. b. gambiense. Topics include role of vector control, and medical interventions, which is used for humanitarian purposes, role of institutions like COCTU (Coordinating Office for the Control of Trypanosomiasis in Uganda), vector control programs from nongovernmental organizations (NGOs), and controlling Tsetse flies.

Epidemics of both forms of human African trypanosomiasis (HAT) are confined to spatially stable foci in Sub-Saharan Africa while tsetse distribution is widespread. Infection rates of Trypanosoma brucei gambiense in tsetse are extremely low and cannot account for the catastrophic epidemics of Gambian HAT (gHAT) seen over the past century. Here we examine the origins of gHAT epidemics and evidence implicating human genetics in HAT epidemiology. We discuss the role of stress causing breakdown of heritable tolerance in silent disease carriers generating gHAT outbreaks and see how peculiarities in the epidemiologies of gHAT and Rhodesian HAT (rHAT) impact on strategies for disease control. [ABSTRACT FROM AUTHOR]

Neglected tropical diseases are a group of protozoan, parasitic, bacterial, and viral diseases endemic in 149 countries causing substantial illness globally. Extreme poverty and warm tropical climates are the 2 most potent forces promoting the spread of neglected tropical diseases. These forces are prevalent in Central and South America, as well as the U.S. Gulf Coast. Advanced cases often require specialized medical imaging for diagnosis, disease staging, and follow-up. This article offers a review of epidemiology, pathophysiology, clinical manifestations, diagnosis (with special attention to medical imaging), and treatment of neglected tropical diseases specific to the Americas. [ABSTRACT FROM AUTHOR]

Background: In Europe, Spain has the highest number of people with Chagas disease (CD). Bolivian migrants account for 81% of the reported cases. One of the priorities in controlling the disease is prevention of mother-to-child transmission. Despite under-diagnosis in Spain being estimated at 90%, there are currently few studies that explore the social and cultural dimensions of this disease. Objective: The aim of this study was to explore the knowledge and experiences of Bolivian women with CD, in order to generate a useful understanding for the design and implementation of public health initiatives. Design: Qualitative study based on semi-structured interviews, triangular groups, and field notes. Participants: Fourteen Bolivian women with CD living in Madrid. Results: The participants were aware that the disease was transmitted through the vector, that it could be asymptomatic, and that it could also be associated with sudden death by heart failure. They opined that the treatment as such could not cure the disease but only slow it down. There was a sense of indifference along with a lack of understanding of the risk of contracting the disease. Participants who presented with symptoms, or those with relatives suffering from the disease, were concerned about fatalities, cardiac problems, and possible vertical transmission. There was also a fear of being rejected by others. The disease was described as something that affected a large number of people but only showed up in a few cases and that too after many years. There was a widespread assumption that it was better not to know because doing so, allows the disease to take hold. Conclusions: Disease risk perception was very low in Bolivian women living in Madrid. This factor, together with the fear of being screened, may be contributing to the current rate of under-diagnosis. [ABSTRACT FROM AUTHOR]

Objective. Chagas disease, a disease caused by Trypanosoma cruzi, disproportionately affects poor people throughout Latin America. In Mexico, assessments of officially reported burden have not been previously reported. To evaluate discontinuity between surveillance data and data from other sources, we used data from the Mexican Ministry of Health to describe the distribution of reported Chagas disease over time in Mexico and compare it with estimates from the literature. Methods. We summarized age and sex differences for Chagas cases and mortality for 1995-2013 and 1982-2010, respectively. We examined the spatial distribution of Chagas disease over time with respect to disease burden. We further compared officially reported figures with estimates from the literature. Results. Among 6,494 officially reported cases, rates of Chagas disease were highest in adults aged 25-44 years (47.3%). Mortality was highest in adults aged ≥45 years (423/495, 85.5%). The data indicated increasing temporal trends for incidence and mortality. The greatest burden occurred in southern states, with increasing spatial distribution over time. Fewer than 900 cases and 40 deaths were officially reported annually, in contrast to estimates from the literature of approximately 69,000 new cases and 25,000 deaths annually. Conclusion. While increasing trends in officially reported data have been observed, large discrepancies in case estimates compromise our understanding of Chagas disease epidemiology. Reported cases based on current practices are not enough to correctly assess the Chagas disease burden and spatial distribution in Mexico. Understanding the true epidemiology of this disease will lead to more focused and successful control and prevention strategies to decrease disease burden. [ABSTRACT FROM AUTHOR]

Introduction: Human African Trypanosomiasis (HAT) is a vector borne parasitic disease transmitted to humans by infected tse-tse flies cause morbidity including delayed child mental development. Reports of nuisance and bites from tse-tse flies by residents of Kachia grazing led to the study to determine the knowledge, practices and prevalence of HAT among residents of the grazing reserve. Methods: We conducted active case search in a cross-sectional study using multi-stage sampling with probability proportionate to size. We administered structured questionnaire on Knowledge, practices relating to HAT prevention and screened for HAT using card agglutination test for Trypanosomiasis (CATT). Knowledge of HAT was scored 0-5 and categorized good (3-5) and poor (0-2) based on score, predisposition to risk of HAT as exposure to =two risk factors and, a case of HAT as any respondent that tested positive on CATT. We analysed data using Epi-info and MS-excel. Results: Of the 300 respondents, mean age 39(±17years) interviewed, 56.3% were males, 12.0% had good knowledge of HAT and 76.3% were exposed to HAT risk factors. Prevention practices included clearing of overgrown bushes around houses (99%), use of insecticidal treated nets (75.7%) and protective clothing (41.0%). Males {Odds Ratio [OR] 5.0; 95% Confidence Interval (CI) 1.8 - 13.6}, age above 40 years {OR 5.0; 95% CI 1.1 - 24.4} and family history of HAT {OR 8.7; 95% CI 2.4 - 32.1} were significantly associated with HAT knowledge. None tested positive on CATT. Conclusion: Despite poor knowledge of HAT, residents practiced HAT preventive measures and zero HAT prevalence was recorded. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The genus Anthocleista of the Gentianaceae family contains 14 species of trees and shrub-like plants distributed in tropical Africa, in Madagascar and on the Comoros. Traditionally, they are commonly used in the treatment of diabetes, hypertension, malaria, typhoid fever, obesity, diarrhea, dysentery, hyperprolactinemia, abdominal pain, ulcer, jaundice, asthma, hemorrhoids, hernia, cancer, wounds, chest pains, inflammations, rheumatism, STDs, infertility and skin diseases. They serve as an anthelmintic, laxative, diuretic and contraceptive. This review aims to provide for the first time a repository of ethnopharmacological information while critically evaluating the relation between the traditional medicinal uses, chemical constituents and pharmacological activities of the Anthocleista species so as to unveil opportunities for future research. Materials and methods A search for relevant information on Anthocleista species was performed on scientific databases (Pubmed, Google Scholar, SciFinder, Web of Science, Scopus, PubChem and other web sources such as The Plant List, Kew Botanical Garden and PROTA) and books, PhD and MSc dissertations for un-published resources. Results Out of the 14 species of Anthocleista , 6 have been reported in literature to be widely used in traditional medicine for the treatment of various ailments. The six species include: A. djalonensis , A. vogelii , A. nobilis , A. grandiflora , A. schweinfurthii , and A. liebrechtsiana . The chemical compounds isolated from Anthocleista species fall into the class of phytochemicals such as secoiridoids, nor-secoiridoids, xanthones, phytosterols, triterpenes, alkaloids, and others of which majority of the compounds were isolated from A. djalonensis and A. vogelii . The in vitro and in vivo pharmacological studies on the crude extracts, fractions and few isolated compounds of Anthocleista species showed antidiabetic, antiplasmodial, antimicrobial, hypotensive, spasmogenic, anti-obesity, antiulcerogenic, analgesic, anti-inflammatory, antioxidant, antitrypanosomal, anthelmintic, fertility, diuretic and laxative activities which supports most of their uses in traditional medicine. However, the bulk of the studies where centered on the antidiabetic, antiplasmodial and antimicrobial activities of Anthocleista species, although the evidence of its antiplasmodial effect was not convincing enough due to the discrepancies between the in vitro and in vivo results. Conclusion A. djalonensis and A. vogelii are potential antidiabetic and antibacterial agents. The antibacterial potency relates to infections or diseases caused by E. coli , S. typhi and S. aureus such as urinary tract infections, typhoid, diarrhea, skin diseases, and food poisoning. Pharmacological research on this genus is quite elementary and limited, thus, more advanced research is necessary to isolate and determine the activities of bioactive compounds in vitro and in vivo , establish their mechanisms of action and commence the process of clinical research. [ABSTRACT FROM AUTHOR]

The article focuses on the post-2015 development agenda, and South-South and triangular cooperation. Topics discussed include the South-South and triangular cooperation as a partnership model for the post-2015 development agenda; the role of developed countries and or multilateral organisations to provide financial support to South-South cooperation; and what role regional fora and financing mechanisms potentially play in implementing the SDGs.

The two new acylphloroglucinol derivatives, methylene-bis-aspidinol AB (1) and mallopposinol (2), together with the nine known compounds, aspidinol B (3), methylene-bis-aspidinol (4), (+)-α-tocopherol (5), lupeol (6), stigmasterol (7), phytol (8), bergenin (9), squalene (11) and methyl gallate (10) were isolated from the leaves of Mallotus oppositifolius . Their structures were elucidated by spectral analysis including MS, 1D and 2D-NMR spectroscopy. In vitro trypanocidal and antileishmanial activities of compounds 1–9 were evaluated. Mallopposinol (2) and aspidinol B (3) displayed weak antileishmanial activities against Leishmania donovani promastigotes, with EC 50 values of 21.3 and 38.8 μM, respectively. Only the methylene-bis-aspidinol (4) exhibited trypanocidal activity against Trypanosoma brucei brucei trypomastigotes (LC 100 = 0.8 μM) similar to the reference drug pentamidine (LC 100 = 0.4 μM). [ABSTRACT FROM AUTHOR]

Five new triterpenoid saponins, heinsiagenin A 3- O- [ α - l -rhamnopyranosyl-(1→2)- β - d -glucopyranosyl-(1→2)]- β - d -glucopyranoside ( 1 ), heinsiagenin A 3- O -[ α - l -rhamnopyranosyl-(1→2) -β- d -glucopyranosyl - (1→2)]-[ β - d -glucopyranosyl-(1→4)]- β - d -glucopyranoside ( 2 ), 2 α -hydroxyheinsiagenin A 3- O -[ α - l -rhamnopyranosyl-(1→2)- β - d -glucopyranosyl-(1→2)]- β - d -glucopyranoside ( 3 ), 2 α -hydroxyheinsiagenin A 3- O -[ β - d -glucopyranosyl-(1→2)]-[ β - d -glucopyranosyl-(1→4)]- β - d -glucopyranoside ( 4 ) and N -(2 S , 3 R , 4 R -3-methyl-4-pentanolid-2-yl)-18-hydroxylanosta-8 (9), 22 E , 24 E -trien-27-amide-3- O -[ α - l -rhamnopyranosyl-(1→2) -β- d -glucopyranosyl - (1→2)]-[ β - d -glucopyranosyl-(1→4)]- β - d -glucopyranoside ( 5 ) were isolated from the aerial parts of Mussaenda luteola Delile (Rubiaceae). Structural elucidation was based on the analysis of spectroscopic data (1D and 2D NMR) and HR-ESI-MS. Compound 1 showed potent antitrypanosomal activity with an IC 50 value of 8.80 μM. Compounds 2–4 showed highly potent antitrypanosomal activity with IC 50 values ranging between (2.57–2.84 μM) and IC 90 values ranging between (3.36–4.35 μM), which are 5 fold greater than the positive control DFMO (IC 50 and IC 90 values of 13.06 and 28.99 μM, respectively). Compounds 1 and 2 showed moderate affinity to μ-opioid receptors with K i values of 9.936 μM and 0.872 μM, respectively compared to a K i value of 1.958 nM for the positive control, naloxone HCl. [ABSTRACT FROM AUTHOR]

Over 100 years have elapsed since the discovery of Chagas disease and there is still much to learn regarding pathogenesis and treatment. Although there are antiparasitic drugs available, such as benznidazole and nifurtimox, they are not totally reliable and often toxic. A recently released negative clinical trial with benznidazole in patients with chronic Chagas cardiomyopathy further reinforces the concerns regarding its effectiveness. New drugs and new delivery systems, including those based on nanotechnology, are being sought. Although vaccine development is still in its infancy, the reality of a therapeutic vaccine remains a challenge. New ECG methods may help to recognize patients prone to developing malignant ventricular arrhythmias. The management of heart failure, stroke and arrhythmias also remains a challenge. Although animal experiments have suggested that stem cell based therapy may be therapeutic in the management of heart failure in Chagas cardiomyopathy, clinical trials have not been promising. [ABSTRACT FROM PUBLISHER]

Dressler (2001:456) characterizes medical anthropology as divided between two poles: the constructivist, which focuses on the “meaning and significance that events have for people,” and the structuralist, which emphasizes socioeconomic processes and relationships. This study synthesizes structuralist and constructivist perspectives by investigating how structural processes impact explanatory models of Chagas disease in a highly endemic area. The research took place from March–June 2013 through the Centro Medico Humberto Parra, a non-profit clinic servicing low income populations in Palacios, Bolivia and surrounding communities. Semistructured interviews (n = 68) and consensus analysis questionnaires (n = 48) were administered to people dealing with Chagas disease. In the interview narratives, respondents link Chagas disease with experiences of marginalization and rural poverty, and describe multilayered impediments to accessing treatment. They often view the disease as incurable, but this reflects inconsistent messages from the biomedical system. The consensus analysis results show strong agreement on knowledge of the vector, ethnomedical treatment, and structural factors related to Chagas disease. In interpreting Chagas disease, respondents account for the structural factors which place them at risk and impede access to care. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Isolona hexaloba (Pierre) Engl. and Diels (Annonaceae) is traditionally used in D.R. Congo against parasitic diseases including malaria. Materials and methods Two crude aqueous extracts, 3 crude methanol extracts and 3 crude 80% ethanol extracts from the leaves, root bark and stem bark together with 12 subfractions from the crude 80% ethanol extracts were evaluated in vitro for their antiprotozoal activity against Trypanosoma brucei brucei, T. cruzi, Leishmania infantum and the chloroquine and pyrimethamine resistant K1 strain of Plasmodium falciparum. Their cytotoxic effects against MRC-5 cell lines were also assessed. Results Results indicated that the most pronounced activities against T. b. brucei were recorded for the crude methanol extracts of root bark (IC50=1.97 µg/ml; SI>32.49) and leaves (IC50=2.65 µg/ml; SI>24.15). Three samples displayed good activity against T. cruzi: the 80% methanol extract of leaves (IC50=8.33 µg/ml; SI>3.92), its petroleum ether fraction (IC50=8.50 µg/ml; SI=2.52) and the crude aqueous extract of the stem bark (IC50=9.31 µg/ml; SI=3.46). The crude aqueous extract of the leaves exhibited a pronounced and selective activity against L. infantum (IC50=2.00 µg/ml; SI>32). The crude methanol extract of leaves (IC50=6.35 µg/ml; SI>10.10) and the 2 dichloromethane soluble fractions of the 80% ethanol extracts from root bark (IC50=6.96 µg/ml; SI=6.1) and stem bark (IC50=8 µg/ml; SI>8.00) showed good activity and selectivity against L. infantum . The most active samples against Plasmodium falciparum K1 were the leaves crude 80% ethanol extract (0.92 µg/ml) and its fractions: alkaline aqueous (IC50=0.27 µg/ml), 90% methanol (0.90 µg/ml) and dichloromethane (1.04 µg/ml), respectively, with promising selectivity indexes of 35

Naphthylisoquinolines are a group of structurally diverse secondary metabolites, consisting of naphthalene and isoquinoline moieties. Naturally occurring naphthylisoquinolines have so far been found only in the small palaeotropic families Dioncophyllaceae and Ancistrocladaceae. They have been shown to exhibit a diverse array of biological activities. Herein, we review the research on the occurrence, isolation, identification, biological activities, and biosynthesis of this class of compounds published from 1995 till now. Moreover, their chemotaxonomic relevance and molecular targets of action have been discussed. More than 125 metabolites are described and 99 references are cited. [ABSTRACT FROM AUTHOR]

The control and eventual elimination of human African trypanosomiasis (HAT) requires the expansion of current control and surveillance activities. A systematic review of the published literature on the costs of HAT prevention, treatment, and control, in addition to the economic burden, was conducted. All studies that contained primary or secondary data on costs of prevention, treatment and control were considered, resulting in the inclusion of 42 papers. The geographically focal nature of the disease and a lack of standardization in the cost data limit the usefulness of the available information for making generalizations across diverse settings. More recent information on the costs of treatment and control interventions for HAT is needed to provide accurate information for analyses and planning. The cost information contained herein can be used to inform rational decision making in control and elimination programs, and to assess potential synergies with existing vector-borne disease control programs, but programs would benefit significantly from new cost data collection. [ABSTRACT FROM AUTHOR]

Six extracts from the roots and the aerial parts of Waltheria indica L. (Malvaceae) were screened for their in vitro antitrypanosomal activity towards Trypanosoma brucei brucei STIB 427 strain, T. brucei rhodesiense STIB 900 and Trypanosoma cruzi Tulahuen C4. The dichloromethane extract from the roots showed the highest activity against T. cruzi (IC 50 = 0.74 μg/mL) as well as a good selectivity index (SI value of 35). Based on these results, this extract was fractionated and led to the isolation of three alkaloids (adouetin X ( 1 ), waltheriones A ( 2 ) and C ( 3 )) and three pentacyclic triterpene derivatives (betulinic acid ( 4 ), 3 β -acetoxy-27- trans -caffeoyloxyolean-12-en-28-oic acid methyl ester ( 5 ) and 3 β -acetoxy-27- cis -caffeoyloxyolean-12-en-28-oic acid methyl ester ( 6 )) identified by 1D and 2D NMR, UV, IR and MS analyses. Among these, waltherione C exhibited the highest and selective antitrypanosomal activity towards T. cruzi (IC 50 = 1.93 μM) with low cytotoxicity (IC 50 = 101.23 μM), resulting in a selectivity index value of 52. Waltherione C conforms to hit activity criteria with respect to T. cruzi as required by the WHO/TDR. [ABSTRACT FROM AUTHOR]

Objectives To review current and emerging tools for Gambiense HAT control and elimination, and propose strategies that integrate these tools with epidemiological evidence. Methods We reviewed the scientific literature to identify contemporary and emerging tools and strategies for controlling and eliminating Gambiense HAT. Through an iterative process involving key stakeholders, we then developed comprehensive scenarios leading to elimination, considering both established and new tools for diagnosis, case treatment and vector control. Results Core components of all scenarios include detecting and treating cases with established or emerging techniques. Relatively more intensive scenarios incorporate vector control. New tools considered include tiny targets for tsetse fly control, use of rapid diagnostic tests and oral treatment with fexinidazole or oxaboroles. Scenarios consider the time when critical new tools are expected to become ready for deployment by national control programmes. Based on a review of the latest epidemiological data, we estimate the various interventions to cover 1380 600 km2 and 56 986 000 people. Conclusions A number of new tools will fill critical gaps in the current armamentarium for diagnosing and treating Gambiense HAT. Deploying these tools in endemic areas will facilitate the comprehensive and sustainable control of the disease considerably and contribute to the ultimate goal of elimination. [ABSTRACT FROM AUTHOR]

Background: Trypanosomiasis is a neglected tropical disease with complex clinical manifestations, tedious diagnosis, and difficult treatments. The drugs available for the treatment of this endemic disease are old, expensive, and associated with other problems including safety and drug resistant parasites. Therefore, there is an urgent need for the development of new, effective, cheap, and safe drugs for its treatment. Plants are potentially rich sources of leads for new drugs against trypanosomiasis. Vitex simplicifolia (Verbenaceae) is used traditionally for the treatment of tooth ache, edema, skin diseases, gout and trypanosomiasis in Nigeria. In a preliminary study, the methanol extract of Vitex simplicifolia was shown to exhibit a pronounced trypanocidal activity against T. b. rhodesiense. The present study was undertaken to investigate the active component responsible for the acclaimed activity of the leaves of Vitex simplicifolia in the traditional treatment of trypanosomiasis in Nigeria and other African countries. Our investigations aim at assessing the plant as a new source of potential trypanocidal compounds. Methods: The crude extracts were prepared from the dried leaves using methanol, successive extraction with hexane, dichloromethane, ethylacetate and butanol was also done. The ethylacetate fraction was further fractionated and compounds isolated using preparative chromatographic technique and their structures were elucidated by NMR, mass spectrometry and comparison with literature data. Trypanocidal activities and cytotoxicity, using rat skeletal myoblast (L6) cells were investigated and their selectivity indices were determined. Results: The chromatographic separations of the methanol extracts gave rise to seven compounds. The isolated compounds 2, 3,6 and 7 exhibited promising trypanocidal activity with IC50 values ranging from 4.7-12.3 µg/ml and cytotoxicity in the range of 1.58- 46.20 µg/ml. Compound 6, however, showed the most selective trypanocidal activity with a selectivity index of 9.8. This is the first report of trypanocidal activity of flavonoids from this plant genus. Conclusions: The isolated compounds from Vitex simplicifolia exhibited noteworthy trypanocidal activities and hence may provide a source of new antitrypanosomal agents. These results also support the traditional use of Vitex simplicifolia in the treatment of trypanosomiasis. This is the first report of trypanocidal effect of flavonoids from this plant genus. [ABSTRACT FROM AUTHOR]

This paper traces the emergence and tensions of an internationally constructed and framed One World-One Health (OWOH) approach to control and attempt to eliminate African Trypanosomiasis in Uganda. In many respects Trypanosomiasis is a disease that an OWOH approach is perfectly designed to treat, requiring an integrated approach built on effective surveillance in animals and humans, quick diagnosis and targeting of the vector. The reality appears to be that the translation of global notions of OWOH down to national and district levels generates problems, primarily due to interactions between: a) international, external actors not engaging with the Ugandan state; b) actors setting up structures and activities parallel to those of the state; c) actors deciding when emergencies begin and end without consultation; d) weak Ugandan state capacity to coordinate its own integrated response to disease; e) limited collaboration between core Ugandan planning activities and a weak, increasingly devolved district health system. These interrelated dynamics result in the global, international interventionalist mode of OWOH undermining the Coordinating Office for Control of Trypanosomiasis in Uganda (COCTU), the body within the Ugandan state mandated expressly with managing a sustainable One Health response to trypanosomiasis outbreaks in Uganda. This does two things, firstly it suggests we need a more grounded, national perspective of OWOH, where states and health systems are acknowledged and engaged with by international actors and initiatives. Secondly, it suggests that more support needs to be given to core coordinating capacity in resource-poor contexts. Supporting national coordinating bodies, focused around One Health, and ensuring that external actors engage with and through those bodies can help develop a sustained, effective OWOH presence in resource-poor countries, where after all most zoonotic disease burden remains. [ABSTRACT FROM AUTHOR]