Assessing the contributions of an urban population health initiative to shift political priority towards cardiovascular health: three case studies from Brazil, Mongolia and Senegal.

BACKGROUND: The urban population health initiative was designed as a multidisciplinary, multisector programme to address cardiovascular (CV) disease, specifically hypertension and its underlying causes in the cities of Ulaanbaatar, Mongolia; Dakar, Senegal; and São Paulo, Brazil. This article aims to provide an overview of the history and dynamics of CV disease policy making in the three countries, to present the policy reform contributions of the initiative and its role in the policy agenda-setting framework/process in each country and to identify the enablers and challenges to the initiative for doing so. METHODS: A qualitative case study was conducted for each setting from November 2020 to January 2021, comprised of a document review, semi-structured in-depth interviews and unstructured interviews with stakeholders involved in the initiative. The literature review included documents from the initiative and the peer-reviewed and grey literature with a total of 188 documents screened. Interviews were conducted with 21 stakeholders. Data collection and thematic analysis was guided by (i) the Kingdon multiple streams conceptual framework with the main themes being CV disease problems, policy, politics and the role of policy entrepreneurs; and (ii) the study question inquiring on the role of the urban population health initiative at the CV disease policy level and enabling and challenging factors to advancing CV disease policy. Data were thematically analysed using the Framework Method. RESULTS: Each setting was characterized by a high hypertension and CV disease burden combined with an aware and proactive political environment. Policy outcomes attributed to the initiative were updating the guidelines and/or algorithms of care for hypertension and including revised physical and nutritional education in school curricula, in each city. Overall, the urban health initiative's effects in the policy arena, were most prominent in Mongolia and Senegal, where the team effectively acted as policy entrepreneur, promoting the solutions/policies in alignment with the most pressing local problems and in strong involvement with the political actors. The initiative was also involved in improving access to CV disease drugs at primary health levels. Its success was influenced by the local governance structures, the proximity of the initiative to the policy makers and the local needs. In Brazil, needs were expressed predominantly in the clinical practice. CONCLUSIONS: This multi-country experience shows that, although the policy and political environment plays its role in shaping initiatives, often the local priority needs are the driving force behind wider change.

Situational analysis of hypertension management at primary health care level in São Paulo, Brazil: population, healthcare professional and health system perspectives.

BACKGROUND: Government-led, population-wide initiatives are crucial for advancing the management of hypertension - a leading cause of cardiovascular disease (CVD) morbidity and mortality. An urban population health initiative was conducted against this backdrop, focussing on hypertension in the primary health system in São Paulo, Brazil. Within the frame of the initiative and under the supervision and leadership of the municipal health authorities, a situational analysis was conducted on the needs in hypertension management, marking the first phase of a Design Thinking process. This article describes the situational analysis process and presents the identified elements to be strengthened considering hypertension diagnosis, treatment and control. METHODS: First, a mixed-methods approach was used, starting with a literature review of municipal hypertension data followed by meetings (N = 20) with the local public health administration to assess health system level components. To investigate activities on hypertension diagnosis, treatment and control, nine primary healthcare units were selected from two districts of São Paulo city- Itaquera and Penha- which received an online form addressed to managers, participated in conversation circles of staff and patients, and underwent shadowing of community health agents. RESULTS: Data gave rise to two main outputs: (i) a patient care journey map; and (ii) a matrix summarizing the identified needs at patient, healthcare professional and health system level for diagnosis, treatment and control of hypertension. Patient awareness and knowledge of hypertension was found to be insufficient and its management needs to be improved. For health professionals, disease awareness, technical training, more time dedicated to patients, and simplified guidelines and clinical decision-making tools for hypertension management were identified as principal needs. The situational analysis found that the healthcare systems efficiency might be improved by establishing defined treatment and care delivery goals with a focus on outcomes and implemented through action plans. CONCLUSIONS: This situational analysis identified several needs related to hypertension control in São Paulo that are in line with global challenges to improve the control of CVD risk factors. Findings were also confirmed locally in an expansion phase of this situational analysis to additional primary care facilities. As a consequence, solutions were designed, promptly taken up and implemented by the municipal health secretariat.

Species composition and insecticide resistance in malaria vectors in Ellibou, southern Côte d'Ivoire and first finding of Anopheles arabiensis in Côte d'Ivoire.

BACKGROUND: Knowing the species composition and insecticide resistance status of the target vector population is important to guide malaria vector control. The aim of this study was to characterize the malaria vector population in terms of species composition, insecticide susceptibility status and potential underlying resistance mechanisms in Ellibou, southern Côte d'Ivoire. METHODS: A 1-year longitudinal entomological survey was conducted using light traps and pyrethroid spray catches to sample adult mosquitoes in combination with larval sampling. The susceptibility status of Anopheles gambiae sensu lato (s.l.) to bendiocarb, deltamethrin, DDT and malathion was assessed using the World Health Organization insecticide susceptibility test. Additionally, An. gambiae specimens were screened for knockdown (kdr) and acetylcholineesterase (ace1) target site resistance alleles, and the expression levels of eight metabolic resistance genes, including seven cytochrome P450 monooxygenases (P450s) and one glutathione S-transferase (GST), measured with reverse transcription quantitative real-time polymerase chain reaction (qPCR). RESULTS: Overall, 2383 adult mosquitoes from 12 different taxa were collected with Culex quinquefasciatus and An. gambiae being the predominant taxa. Molecular identification of An. gambiae s.l. revealed the presence of Anopheles arabiensis, Anopheles coluzzii, An. gambiae sensu stricto (s.s.) and Anopheles coluzzii/An. gambiae s.s. hybrids. Anopheles gambiae mosquitoes were resistant to all insecticides except malathion. PCR diagnostics revealed the presence of ace1-G280S and the kdr L995F, L995S and N1570Y target-site mutations. Additionally, several genes were upregulated, including five P450s (i.e., CYP6P3, CYP6M2, CYP9K1, CYP6Z1, CYP6P1) and GSTE2. CONCLUSION: This is the first documented presence of An. arabiensis in Côte d'Ivoire. Its detection - together with a recent finding further north of the country - confirms its existence in the country, which is an early warning sign, as An. arabiensis shows a different biology than the currently documented malaria vectors. Because the local An. gambiae population was still susceptible to malathion, upregulation of P450s, conferring insecticide resistance to pyrethroids, together with the presence of ace1, suggest negative cross-resistance. Therefore, organophosphates could be an alternative insecticide class for indoor residual spraying in the Ellibou area, while additional tools against the outdoor biting An. arabiensis will have to be considered.

Implementing a multisector public-private partnership to improve urban hypertension management in low-and middle- income countries.

BACKGROUND: Cardiovascular disease presents an increasing health burden to low- and middle-income countries. Although ample therapeutic options and care improvement frameworks exist to address its prime risk factor, hypertension, blood pressure control rates remain poor. We describe the results of an effectiveness study of a multisector urban population health initiative that targets hypertension in a real-world implementation setting in cities across three continents. The initiative followed the "CARDIO4Cities" approach (quality of Care, early Access, policy Reform, Data and digital technology, Intersectoral collaboration, and local Ownership). METHOD: The approach was applied in Ulaanbaatar in Mongolia, Dakar in Senegal, and São Paulo in Brazil. In each city, a portfolio of evidence-based practices was implemented, tailored to local priorities and available data. Outcomes were measured by extracting hypertension diagnosis, treatment and control rates from primary health records. Data from 18,997 patients with hypertension in primary health facilities were analyzed. RESULTS: Over one to two years of implementation, blood pressure control rates among enrolled patients receiving medication tripled in São Paulo (from 12·3% to 31·2%) and Dakar (from 6·7% to 19·4%) and increased six-fold in Ulaanbaatar (from 3·1% to 19·7%). CONCLUSIONS: This study provides first evidence that a multisectoral population health approach to implement known best-practices, supported by data and digital technologies, and relying on local buy-in and ownership, can improve hypertension control in high-burden urban primary care settings in low-and middle-income countries.

Deconstructing design thinking as a tool for the implementation of a population health initiative.

BACKGROUND: The translation of evidence-based practices and rapid uptake of innovations into global health practice is challenging. Design thinking is a consultative process involving multiple stakeholders and has been identified as a promising solution to create and apply implementation strategies in complex environments like health systems. METHODS: We conducted a process evaluation of a real-world example, namely an initiative to innovate hypertension screening, diagnosis and care in São Paulo, Brazil. The parameters of the evaluation were informed by a specification rubric and categorization system, recommended for the investigation of implementation strategies, and the double-diamond conceptual framework to describe and examine the strategic architecture and nature of the design thinking approach, with particular emphasis on identifying potential areas of "value-add" particular to the approach. The retrospective evaluation was performed by an independent partner who had not been involved in the setting up and implementation of the design thinking process. RESULTS: The evaluation unveiled a dense catalogue of strategically driven, mostly theoretically based, activities involving all identified health system stakeholders including patients. Narrative reconstruction illuminated the systematic and coherent nature of this approach, with different resulting actions progressively accounting for all relevant layers of the health system to engineer a broad selection of specific implementation solutions. The relevance of the identified features and the mechanics used to promote more successful implementation practices was manifested in several distinct ways: design thinking offered a clear direction on which innovations really mattered and when, as well as several new dimensions for consideration in the development of an innovation mindset amongst stakeholders. It thereby promoted relationship quality in terms of familiarity and trust, and commitment to evidence-based enquiry and action. Design thinking was also able to navigate the territory between the need for intervention "fidelity" versus "adaptation" and provide the operational know-how to face familiar implementation hurdles. Lastly, it brought a new kind of skill set to the public health stakeholders that incorporated diplomacy, multidisciplinary approaches and management sciences-skills that are considered necessary but not yet widely taught as part of public health training. CONCLUSIONS: Design thinking is a sound and viable tool to use as part of an implementation strategy for engaging with health system stakeholders and successfully translating evidence-based practices and new innovations into routine practice, thereby addressing an important knowledge-practice gap and, more broadly, contributing to the strategic repertoire available to implementation science.

Fostering cardiovascular health at work - case study from Senegal.

BACKGROUND: Of the 15 million annual premature deaths from non-communicable diseases (NCDs), 85% occur in low- and middle-income countries (LMICs). Affecting individuals in the prime of their lives, NCDs impose severe economic damage to economies and businesses, owing to the high mortality and morbidity within the workforce. The Novartis Foundation urban health initiative, Better Hearts Better Cities, was designed to improve cardiovascular health in Dakar, Senegal through a combination of interventions including a workplace health program. In this study, we describe the labor policy environment in Senegal and the outcomes of a Novartis Foundation-supported multisector workplace health coalition bringing together volunteering private companies. METHODS: A mixed method design was applied between April 2018 and February 2020 to evaluate the workplace health program as a case study. Qualitative methods included a desk review of documents relevant to the Senegalese employment context and work environment and in-depth interviews with eight key informants including human resource representatives and physicians working in the participating companies. Quantitative methods involved an analysis of workplace health program indicators, including data on diagnosis, treatment and control of hypertension in employees, provided by the coalition companies, and a cost estimate of NCD-related ill-health as compared to the investment needed for hypertension screening and awareness raising events. RESULTS: Senegal has a legal and regulatory system that ensures employee protection, supports social security benefits, and promotes health and hygiene in companies. The Dakar Workplace Health Coalition comprised 18 companies, with a range of staff between 300 and 4'220, covering 36'268 employees in total. Interviews suggested that the main enablers for workplace program success were strong leadership support within the company and a central coordination mechanism for the program. The main barrier to monitor progress and outcomes was the reluctance of companies to share data. Four companies provided aggregated anonymized cohort data, documenting a total of 21'392 hypertension screenings and an increasing trend in blood pressure control (from 34% in Q4 2018 to 39% in Q2 2019) in employees who received antihypertensive treatment. CONCLUSION: Evidence on workplace health and wellness programs in Africa is scarce. This study highlights how private sector companies can play a significant role in improving cardiovascular population health in LMICs.

The consequences of compromising the EU's free movement of persons principle on Swiss research: how to survive constrained access to regional funding.

Between 2014 and 2016, Switzerland's access to some of the EU funding was limited after a referendum against mass immigration was accepted and the country refused to sign the free movement accord to the EU's newest member, Croatia. It is well documented that Switzerland has suffered from a drop in participation, funding and a decrease in consortium lead positions. However, there is no account of the consequences on institutional level. We therefore aimed at describing the immediate- and longer-term impact of the partial association status to the Swiss Tropical and Public Health Institute (Swiss TPH) and to identify key strategies for minimizing institutional damage during a limited access period to a key regional funding source. A quantitative analysis of the institute's grants database, from 2007 to 2019, did not show any clear trends related to the partial association status of Switzerland for funding and projects awarded. The qualitative outcomes changed along the timeline assessed; whereas in 2014 a range of negative effects were stated by Swiss TPH researchers, a survey conducted in 2019 with Swiss TPH applicants and project partners to Horizon 2020, revealed that most project leaders felt that the partial association did neither affect their external partners' willingness to collaborate nor Swiss TPH's role in the proposal or consortium. On the other hand, the institutional strategic goal of taking on consortia leads was delayed by several years as a direct consequence of the partial association. Also, the exclusion from European research networks and the lack of consultation of expertise by the European partner institutions was widely seen as damaging. A policy of favouring long-term partnerships over ad-hoc collaborations, along with constant and trustful communication, as immediate mitigation measure, helped averting some of the reputational and access damage. Moreover, the Swiss TPH business model based on a three-way strategy of research, education and services has proven highly viable allowing to build a large pool of potential funding sources internationally, resulting in relative resilience in terms of income lost.

Incorporating operational research in programmes funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria in four sub-Saharan African countries.

BACKGROUND: The current study builds upon a previous situation analysis of the extent to which grants from the Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund) are being utilized to support operational research and implementation research (OR/IR) activities in recipient countries. The objective of this follow-up study was to identify approaches and pathways to implement an OR component into grants to the Global Fund, in four sub-Saharan African countries. Special focus was given to the Structured Operational Research and Training IniTiative (SORT IT). METHODS: The conceptual framework was based on an analysis to identify elements supporting and blocking the integration of OR, called force field analysis, and a behavioural change assessment covering aspects such as opportunity, motivation, capability and triggers to do the integration. Data were collected through online surveys and stakeholder interviews both via telephone/online conference tools and in person in four countries with a high burden of malaria and tuberculosis. These countries were Ghana, Sierra Leone, the United Republic of Tanzania and Zimbabwe. The stakeholders included programme managers, implementation partners, representatives from international organisations, academic and governmental research institutions and other individuals involved in the countries' needs assessment and National Strategic Plan development. RESULTS: We identified opportunities to integrate OR into the countries' programmes during the funding process, the country's needs assessment being the most important one, including the need of OR-related capacity. Both the force field analysis and the behavioural change assessment showed that the necessary elements to integrate OR were present in the countries. Motivation, capability and efficiency were found to be a managerial value omnipresent across stakeholders. However, those elements were influenced by the tendency to favour tangible assets over any abstract ones, such as increasing organisational capacity in OR. CONCLUSIONS: In each of the countries assessed, there is potential to integrating OR into the programmes supported by the Global Fund. However, given the relative lack of OR-related capacity and skills encountered, a capacity strengthening tool, such as SORT IT, would be of benefit helping to identify and carry forward OR activities sustainably.

Buruli ulcer in southern Côte D'ivoire: dynamic schemes of perception and interpretation of modes of transmission.

Buruli ulcer (BU) belongs to the group of neglected tropical diseases and constitutes a public health problem in many rural communities in Côte d'Ivoire. The transmission patterns of this skin infection are poorly defined, hence the current study aimed to contribute to the understanding, perceptions and interpretations of its mode of transmission using a socio-environmental approach. Social and environmental risk factors that may expose people to infection, and the dynamics of local transfer of knowledge and practices related to BU, were assessed in two endemic locations in southern Côte d'Ivoire, i.e. Taabo and Daloa. Data were generated by the administration of a household questionnaire (N=500) between February and June 2012 to assess how the population perceived transmission of BU, focus group discussions with local communities (N=8) to analyse ideologies regarding transmission patterns and semi-structured interviews with patients or their parents, former BU patients and traditional healers (N=30). The interviewees' empirical knowledge of the disease was found to be close to its biomedical description. Their aetiological perception of the disease was linked to natural (e.g. dirty water, insects) and supernatural (e.g. witchcraft, fate) causes. Some informants attributed the spread of the disease to recently immigrated neighbouring communities whose arrival coincided with an increase in reported BU cases. However, the general consensus seemed to be that the main mode of transmission was contact with infested soil or ulcerated wounds. The participants were aware that BU was a socio-environmental problem in these endemic areas, offering a good starting point for educational campaigns for at-risk communities. Buruli ulcer control programmes should therefore include educational campaigns and Water, Sanitation and Hygiene (WASH) interventions for those at risk in affected communities.

Effects of Vancomycin and Ciprofloxacin on the NMRI Mouse Metabolism.

The reduction in gut microbiota diversity is associated with a range of human diseases. Overuse of antibiotics has been associated with a diminished gut-microbial diversity in humans and may promote microbiota-associated negative effects to physical health, such as the metabolic syndrome-cluster of diseases and mental illnesses. There is a pressing need to deepen the understanding of the effects of antibiotics at the biochemical level. The current study investigated metabolic effects of two widely prescribed antibiotics-vancomycin and ciprofloxacin-on biofluids and brain tissue samples of NMRI female mice using a 1H nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling approach. While both antibiotics significantly affected the host metabolic signatures of urine and feces, only ciprofloxacin induced metabolic changes in plasma. Metabolic perturbations were pronounced 1 day post-treatment, reverting back to baseline at day 20 post-treatment. Both antibiotics induced changes in the choline metabolism, host-microbial cometabolites, short chain fatty acid production, and protein/purine degradation. The metabolic profiles of brain tissue aqueous extracts did not show any antibiotics-related changes by day 20 post-treatment. The data suggest that the metabolic disruptions in biofluids caused by antibiotics are reversed by day 20 post-treatment when compared to the pre-treatment profiles.

Association of riverine prawns and intermediate host snails and correlation with human schistosomiasis in two river systems in south-eastern Côte d'Ivoire.

The current emphasis of schistosomiasis control is placed on preventive chemotherapy using praziquantel. However, reinfection may occur rapidly in the absence of complementary interventions. Recent studies from Senegal suggest that predatory prawns might feed on intermediate host snails and thus impact on schistosomiasis transmission. We designed a study with four repeated cross-sectional surveys pertaining to prawns and snails, coupled with a single cross-sectional parasitological survey among humans. We assessed for potential associations between the presence/density of prawns and snails and correlation with Schistosoma infection in a composite sample of school-aged children and adults. The study was carried out between October 2015 and December 2016 in 24 villages located near the Agnéby and Mé coastal river systems in south-eastern Côte d'Ivoire. At each site, snails and prawns were collected, and in each village, 150 individuals were subjected to stool and urine examination for the diagnosis of Schistosoma mansoni and S. haematobium. We found peaks of relative abundance of intermediate host snails in the villages of the Agnéby River system, while predatory prawns were predominantly recorded in the Mé River system. A negative association was observed between intermediate host snail densities and riverine prawns; however, no pattern was found between this trend in the predator-prey relationship and the prevalence of human schistosomiasis.

Research productivity and main publishing institutions in Côte d'Ivoire, 2000-2016.

BACKGROUND: The research productivity of countries commonly grouped within sub-Saharan Africa is as diverse as their cultural, economic, linguistic, political, and social profiles. While South Africa has been the science hub on the subcontinent for decades, publishing original research articles in the thousands, Mauritania struggles to have a single publication in international indexed journals in any given year. Detailed country-specific accounts on the co-evolution of research productivity and demographic and economic indicators from sub-Saharan Africa are lacking and render an accurate evaluation and cross-country comparison of internal research progress challenging. METHODS: We assessed the research productivity of Côte d'Ivoire, a francophone West African country that has gone through considerable socio-political unrest, for the period 2000-2016, and determined the main publishing institutions. We considered original research articles extracted from PubMed and Web of Science Core Collection, emphasizing life sciences and biomedical sciences. RESULTS: We found the quantity of publications doubling from 4.1 to 8.5 per million population and the 'total product' - a measure for quantity and quality of published articles - rising from 0.8 to 22.1 per million population between 2000 and 2016. Since 2010 there was a marked increase in the proportion of English publications and a concomitant drop in the proportion of articles with Ivorian first and last authors. The percentage of foreign author contribution increased from 38.7% in 2000 to 71.6% in 2016, suggesting an 'internationalization' of the country's research production and output. Mixed authorship compared with 'Ivorian only' showed higher representation in journals with an official impact factor by Web of Science with proportions of 73% versus 28% for 2008 and 91% versus 45% for 2016. Two universities and university hospitals and three autonomous research institutions were consistently among the top 10 institutions publishing peer-reviewed material in three selected years (2000, 2008, and 2016). The main features of the most successful publishing institutions were research staff size, diversification of research portfolio and funding, multiple research bases across the country, and established and productive partnerships with foreign institutions. CONCLUSION: Since the turn of the millennium, research productivity in Côte d'Ivoire has steadily grown at an above regional and global rate despite recurring economic pressures and sociopolitical unrest. We have observed benefits of internationalization throughout this current analysis reaching from improved publishing standards to increasing resilience of research institutions in times of crisis.

Metabolic, immune, and gut microbial signals mount a systems response to Leishmania major infection.

Parasitic infections such as leishmaniasis induce a cascade of host physiological responses, including metabolic and immunological changes. Infection with Leishmania major parasites causes cutaneous leishmaniasis in humans, a neglected tropical disease that is difficult to manage. To understand the determinants of pathology, we studied L. major infection in two mouse models: the self-healing C57BL/6 strain and the nonhealing BALB/c strain. Metabolic profiling of urine, plasma, and feces via proton NMR spectroscopy was performed to discover parasite-specific imprints on global host metabolism. Plasma cytokine status and fecal microbiome were also characterized as additional metrics of the host response to infection. Results demonstrated differences in glucose and lipid metabolism, distinctive immunological phenotypes, and shifts in microbial composition between the two models. We present a novel approach to integrate such metrics using correlation network analyses, whereby self-healing mice demonstrated an orchestrated interaction between the biological measures shortly after infection. In contrast, the response observed in nonhealing mice was delayed and fragmented. Our study suggests that trans-system communication across host metabolism, the innate immune system, and gut microbiome is key for a successful host response to L. major and provides a new concept, potentially translatable to other diseases.

Changes in metabolic phenotypes of Plasmodium falciparum in vitro cultures during gametocyte development.

BACKGROUND: Gametocytes are the Plasmodium life stage that is solely responsible for malaria transmission. Despite their important role in perpetuating malaria, gametocyte differentiation and development is poorly understood. METHODS: To shed light on the biochemical changes that occur during asexual and gametocyte development, metabolic characterization of media from in vitro intra-erythrocytic Plasmodium falciparum cultures was performed throughout gametocyte development by applying 1H nuclear magnetic spectroscopy, and using sham erythrocyte cultures as controls. Spectral differences between parasite and sham cultures were assessed via principal component analyses and partial-least squares analyses, and univariate statistical methods. RESULTS: Clear parasite-associated changes in metabolism were observed throughout the culture period, revealing differences between asexual parasites and gametocyte stages. With culture progression and development of gametocytes, parasitic release of the glycolytic end products lactate, pyruvate, alanine, and glycerol, were found to be dramatically reduced whilst acetate release was greatly increased. Also, uptake of lipid moieties CH(2), CH(3), and CH = CH-CH(2)-CH(2) increased throughout gametocyte development, peaking with maturity. CONCLUSIONS: This study uniquely presents an initial characterization of the metabolic exchange between parasite and culture medium during in vitro P. falciparum gametocyte culture. Results suggest that energy metabolism and lipid utilization between the asexual stages and gametocytes is different. This study provides new insights for gametocyte-specific nutritional requirements to aid future optimization and standardization of in vitro gametocyte cultivation, and highlights areas of novel gametocyte cell biology that deserve to be studied in greater detail and may yield new targets for transmission-blocking drugs.

An Intersectoral Approach to Hypertension Care: Solutions for Improving Blood Pressure Control in São Paulo, Brazil.

BACKGROUND: Hypertension is the leading risk factor for cardiovascular diseases (CVDs) and a major public health issue worldwide. In Brazil, it affects approximately 52.5% of the adult population. We describe the solutions package and the impact of a population health initiative in São Paulo city, following the CARDIO4Cities approach for the management of cardiovascular risk. METHODS: Using a design thinking approach, interventions were developed with a coalition of local and international stakeholders to address needs of patients, healthcare professionals, and the health system. The resulting solution package was checked to comply with guidelines for non-communicable disease and hypertension management. Clinical impact was measured by extracting the hypertension cascade of care-monitored, diagnosis, treatment, and control-from medical records. RESULTS: Under the leadership of the municipal health authorities, nine solutions were piloted and scaled across the city. Solutions conform with local and international best-practices. Between October 2017 and December 2021, 11,406 patient records were analyzed. Results showed a 40% increase in monitored patients (patients with at least one blood pressure, BP, measurement); reduced proportions of patients diagnosed among those with available BP measurements (72%-53%) and treated among diagnosed (93%-85%); and an improvement in controlled patients among those receiving treatment (16%-27%). CONCLUSIONS: The solution package described in this study was correlated with increased BP control. The implementation methodology and results add to the body of real-world evidence supporting population health implementation science in Brazil and beyond.

Metabolic characterization of Leishmania major infection in activated and nonactivated macrophages.

Infection with Leishmania spp. can lead to a range of symptoms in the affected individual, depending on underlying immune-metabolic processes. The macrophage activation state hereby plays a key role. Whereas the l-arginine pathway has been described in detail as the main biochemical process responsible for either nitric oxide mediated parasite killing (classical activation) or amplification of parasite replication (alternative activation), we were interested in a wider characterization of metabolic events in vitro. We therefore assessed cell growth medium, parasite extract, and intra- and extracellular metabolome of activated and nonactivated macrophages, in presence and absence of Leishmania major. A metabolic profiling approach was applied combining 1H NMR spectroscopy with multi- and univariate data treatment. Metabolic changes were observed along both conditional axes, that is, infection state and macrophage activation, whereby significantly higher levels of potential parasite end products were found in parasite exposed samples including succinate, acetate, and alanine, compared to uninfected macrophages. The different macrophage activation states were mainly discriminated by varying glucose consumption. The presented profiling approach allowed us to obtain a metabolic snapshot of the individual biological compartments in the assessed macrophage culture experiments and represents a valuable read out system for further multiple compartment in vitro studies.

Systematic evaluation of extraction methods for multiplatform-based metabotyping: application to the Fasciola hepatica metabolome.

Combining data from multiple analytical platforms is essential for comprehensive study of the molecular phenotype (metabotype) of a given biological sample. The metabolite profiles generated are intrinsically dependent on the analytical platforms, each requiring optimization of instrumental parameters, separation conditions, and sample extraction to deliver maximal biological information. An in-depth evaluation of extraction protocols for characterizing the metabolome of the hepatobiliary fluke Fasciola hepatica , using ultra performance liquid chromatography and capillary electrophoresis coupled with mass spectroscopy is presented. The spectrometric methods were characterized by performance, and metrics of merit were established, including precision, mass accuracy, selectivity, sensitivity, and platform stability. Although a core group of molecules was common to all methods, each platform contributed a unique set, whereby 142 metabolites out of 14,724 features were identified. A mixture design revealed that the chloroform:methanol:water proportion of 15:59:26 was globally the best composition for metabolite extraction across UPLC-MS and CE-MS platforms accommodating different columns and ionization modes. Despite the general assumption of the necessity of platform-adapted protocols for achieving effective metabotype characterization, we show that an appropriately designed single extraction procedure is able to fit the requirements of all technologies. This may constitute a paradigm shift in developing efficient protocols for high-throughput metabolite profiling with more-general analytical applicability.

Systems parasitology: effects of Fasciola hepatica on the neurochemical profile in the rat brain.

We characterize the integrated response of a rat host to the liver fluke Fasciola hepatica using a combination of (1)H nuclear magnetic resonance spectroscopic profiles (liver, kidney, intestine, brain, spleen, plasma, urine, feces) and multiplex cytokine markers of systemic inflammation. Multivariate mathematical models were built to describe the main features of the infection at the systems level. In addition to the expected modulation of hepatic choline and energy metabolism, we found significant perturbations of the nucleotide balance in the brain, together with increased plasma IL-13, suggesting a shift toward modulation of immune reactions to minimize inflammatory damage, which may favor the co-existence of the parasite in the host. Subsequent analysis of brain extracts from other trematode infection models (i.e. Schistosoma mansoni, and Echinostoma caproni) did not elicit a change in neural nucleotide levels, indicating that the neural effects of F. hepatica infection are specific. We propose that the topographically extended response to invasion of the host as characterized by the modulated global metabolic phenotype is stratified across several bio-organizational levels and reflects the direct manipulation of host-nucleotide balance.

Global metabolic responses of mice to Trypanosoma brucei brucei infection.

Human African trypanosomiasis (HAT) is transmitted by tsetse flies and, if untreated, is fatal. Treatment depends on infection stage, and early diagnosis is crucial for effective disease management. The systemic host biochemical changes induced by HAT that enable biomarker discovery or relate to therapeutic outcome are largely unknown. We have characterized the multivariate temporal responses of mice to Trypanosoma brucei brucei infection, using (1)H nuclear magnetic resonance (NMR) spectroscopic metabolic phenotyping of urine and plasma. Marked alterations in plasma metabolic profiles were detected already 1 day postinfection. Elevated plasma concentrations of lactate, branched chain amino acids, and acetylglycoprotein fragments were noted. T. brucei brucei-infected mice also had an imbalance of plasma alanine and valine, consistent with differential gluconeogenesis (parasite)-ketogenesis (host) pathway counterflux, involving stimulated host glycolysis, ketogenesis, and enhanced lipid oxidation in the host. Histopathologic evidence of T. brucei brucei-induced extramedullary hepatic hemopoiesis, renal interstitial nephritis, and a provoked inflammatory response was also noted. Metabolic disturbance of gut microbiotal activity was associated with infection, as indicated by changes in the urinary concentrations of the microbial co-metabolites, including hippurate. Concluding, parasite infection results in multiple systemic biochemical effects in the host and disturbance of the symbiotic gut microbial metabolic interactions. Investigation of these transgenomic metabolic alterations may underpin the development of new diagnostic criteria and metrics of therapeutic efficacy.