Reach and effectiveness of a HEARTS hypertension pilot project in Guatemala.

The World Health Organization Global Hearts initiative (HEARTS) and technical package aim to improve the primary health care management of hypertension and other risk factors for cardiovascular disease at the population level. This study describes the first HEARTS implementation pilot project in Guatemala's Ministry of Health (MOH) primary health care system. This pilot began in April 2022 in six primary health care facilities in three rural indigenous municipalities. The project consisted of HEARTS-aligned strategies adapted to enhance program sustainability in Guatemala. Outcomes were defined using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. The primary reach outcome was treatment count, defined as the absolute number of patients per month receiving medication treatment for hypertension. The primary effectiveness outcomes were mean systolic blood pressure (BP), mean diastolic BP, and proportion of patients with BP control (<130/80 mmHg). In the first month of the post-implementation period, there was a statistically significant increase of 25 patients treated per month above the baseline of 20 to 25 patients (P = .002), followed by a significant increase of 2.4 additional patients treated each month (P = .005) thereafter. The mean change in systolic BP was -4.4 (95% CI, -8.2 to -0.5; P = 0.028) mmHg, and the mean change in diastolic BP was -0.9 (95% CI, -2.8 to 1.1; P = .376) mmHg. The proportion of the cohort with BP control increased from 33.4% at baseline to 47.1% at 6 months (adjusted change, 13.7%; 95% CI, 2.2% to 25.2%; P = .027). These findings support the feasibility of implementing the HEARTS model for BP control throughout the MOH primary health care system, which is where most Guatemalans with hypertension seek care.

El paquete técnico de la Iniciativa Global Hearts ("HEARTS") de la Organización Mundial de la Salud tiene como objetivo mejorar el control de la hipertensión y de otros factores de riesgo de enfermedades cardiovasculares a nivel poblacional en el ámbito de la atención primaria de salud de salud. Este estudio describe el primer proyecto piloto de implementación de HEARTS en el sistema de atención primaria de salud del Ministerio de Salud de Guatemala. El proyecto, que comenzó en abril del 2022 en seis centros de atención primaria de salud pertenecientes a tres municipios rurales indígenas, consistió en estrategias alineadas con HEARTS y adaptadas para mejorar la sostenibilidad del programa en Guatemala. Los criterios de valoración de los resultados se definieron mediante el marco estandarizado de evaluación de cobertura, efectividad, adopción, implementación y mantenimiento (RE-AIM, por su sigla en inglés). El criterio principal de la cobertura fue la cantidad de tratamientos, definida como el número absoluto de pacientes por mes que recibían tratamiento farmacológico para la hipertensión. Los criterios principales de la efectividad fueron la media de presión arterial (PA) sistólica, la media de PA diastólica y la proporción de pacientes con un control de la PA (<130/80 mmHg). En el primer mes del período posterior a la implementación, se registró un aumento estadísticamente significativo de 25 pacientes tratados al mes por encima del valor inicial de 20 a 25 pacientes (n = 25; p = 0,002), seguido de un aumento significativo de 2,4 pacientes adicionales tratados al mes (p = 0,005) posteriormente. El cambio en la media de la PA sistólica fue de -4,4 (IC del 95%: -8,2 a -0,5); p = 0,028) mmHg, en tanto que el cambio en la media de la PA diastólica fue de -0,9 (IC del 95%, -2,8 a 1,1); p = 0,376) mmHg. La proporción de la cohorte con control de la PA aumentó del 33,4% al inicio al 47,1% a los seis meses (cambio ajustado, 13,7%; IC del 95%, 2,2% a 25,2%; p = 0,027). Estos resultados respaldan la viabilidad de la implementación del modelo HEARTS para el control de la PA en la totalidad del sistema de atención primaria de salud del Ministerio de Salud de Guatemala, al que acude en busca de atención la mayoría de las personas con hipertensión.

O pacote de medidas técnicas da iniciativa Global Hearts ("HEARTS") da Organização Mundial da Saúde tem como objetivo melhorar o controle da hipertensão arterial e de outros fatores de risco para doenças cardiovasculares na atenção primária à saúde em nível populacional. Este estudo descreve o primeiro projeto-piloto de implementação da iniciativa HEARTS no sistema de atenção primária à saúde do Ministério da Saúde da Guatemala. O projeto-piloto começou em abril de 2022 em seis estabelecimentos de atenção primária à saúde em três municípios indígenas rurais. O projeto consistiu em estratégias alinhadas à iniciativa HEARTS e adaptadas para melhorar a sustentabilidade do programa na Guatemala. Os desfechos foram definidos usando a estrutura de avaliação RE-AIM (sigla em inglês para alcance, efetividade, adoção, implementação e manutenção). O desfecho primário de alcance foi a quantidade de tratamentos, definida como o número absoluto de pacientes por mês que receberam tratamento medicamentoso para hipertensão. Os desfechos primários de efetividade foram pressão arterial (PA) sistólica média, PA diastólica média e proporção de pacientes com controle da PA (<130/80 mmHg). No primeiro mês do período pós-implementação, houve um aumento estatisticamente significante de 25 pacientes tratados por mês acima da linha de base de 20 a 25 pacientes (n = 25; P = 0,002), seguido de um aumento significante de 2,4 pacientes adicionais tratados a cada mês (P = 0,005) depois disso. A mudança média na PA sistólica foi de −4,4 (intervalo de confiança [IC] de 95%: −8,2 a −0,5; P = 0,028) mmHg, e a mudança média na PA diastólica foi de −0,9 (IC de 95%: −2,8 a 1,1; P = 0,376) mmHg. A proporção da coorte com controle da PA aumentou de 33,4% na linha de base para 47,1% após 6 meses (mudança ajustada, 13,7%; IC de 95%: 2,2% a 25,2%; P = 0,027). Esses achados apoiam a viabilidade da implementação do modelo HEARTS para o controle da PA em todo o sistema de atenção primária à saúde do Ministério da Saúde da Guatemala, no qual a maioria dos indivíduos com hipertensão arterial procura atendimento.

IL-10 Impairs Local Immune Response in Lung Granulomas and Lymph Nodes during Early Mycobacterium tuberculosis Infection.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, continues to be a major global health problem. Lung granulomas are organized structures of host immune cells that function to contain the bacteria. Cytokine expression is a critical component of the protective immune response, but inappropriate cytokine expression can exacerbate TB. Although the importance of proinflammatory cytokines in controlling M. tuberculosis infection has been established, the effects of anti-inflammatory cytokines, such as IL-10, in TB are less well understood. To investigate the role of IL-10, we used an Ab to neutralize IL-10 in cynomolgus macaques during M. tuberculosis infection. Anti-IL-10-treated nonhuman primates had similar overall disease outcomes compared with untreated control nonhuman primates, but there were immunological changes in granulomas and lymph nodes from anti-IL-10-treated animals. There was less thoracic inflammation and increased cytokine production in lung granulomas and lymph nodes from IL-10-neutralized animals at 3-4 wk postinfection compared with control animals. At 8 wk postinfection, lung granulomas from IL-10-neutralized animals had reduced cytokine production but increased fibrosis relative to control animals. Although these immunological changes did not affect the overall disease burden during the first 8 wk of infection, we paired computational modeling to explore late infection dynamics. Our findings support that early changes occurring in the absence of IL-10 may lead to better bacterial control later during infection. These unique datasets provide insight into the contribution of IL-10 to the immunological balance necessary for granulomas to control bacterial burden and disease pathology in M. tuberculosis infection.

A comparative study of human-and rhesus-specific antithymocyte globulins in Rhesus macaques.

Rabbit antithymocyte globulin (RATG) preparations are widely used in transplantation. They are developed in vivo against thymocytes and contain polyclonal antibodies specific for myriad cellular targets. The rhesus monkey is commonly used as a preclinical transplant model, but the fidelity of commercially available human-specific RATGs to anticipate the effects of RATGs in rhesus has not been established. We therefore developed two rhesus-specific ATGs (rhATG) and compared them to human-specific RATG (huATG, Thymoglobulin® ) in rhesus monkeys, assessing the magnitude and phenotype of depletion peripherally and in lymph nodes. Four primates were assigned to each group and received 20 mg/kg of drug. Depletion, repopulation, and changes in lymphocyte subsets were evaluated in peripheral blood and lymph nodes by flow cytometry over four months. We observed similar qualitative changes in lymphocyte subsets, but a generally more profound depletion with huATG compared to either rhATG. Peripheral homeostatic proliferation rather than thymic output was the major mechanism for repopulation with all RATGs. Repopulation was slower but qualitatively similar when examining RATGs in additional animals receiving concomitant chronic immunosuppression. Depletional induction is similar to human- and rhesus-specific RATGs in rhesus macaques. Both rhesus- and human-specific agents appear appropriate for preclinical modeling of clinical RATG use.

Anti-CD40 antibody 2C10 binds to a conformational epitope at the CD40-CD154 interface that is conserved among primate species.

The antagonistic anti-CD40 antibody, 2C10, and its recombinant primate derivative, 2C10R4, are potent immunosuppressive antibodies whose utility in allo- and xenotransplantation have been demonstrated in nonhuman primate studies. In this study, we defined the 2C10 binding epitope and found only slight differences in affinity of 2C10 for CD40 derived from four primate species. Staining of truncation mutants mapped the 2C10 binding epitope to the N-terminal portion of CD40. Alanine scanning mutagenesis of the first 60 residues in the CD40 ectodomain highlighted key amino acids important for binding of 2C10 and for binding of the noncross-blocking anti-CD40 antibodies 3A8 and 5D12. All four 2C10-binding residues defined by mutagenesis clustered near the membrane-distal tip of CD40 and partially overlap the CD154 binding surface. In contrast, the overlapping 3A8 and 5D12 epitopes map to an opposing surface away from the CD154 binding domain. This biochemical characterization of 2C10 confirms the validity of nonhuman primate studies in the translation of this therapeutic antibody and provides insight its mechanism of action.

Social exclusion and universal health coverage: health care rights and citizen-led accountability in Guatemala and Peru.

BACKGROUND: While equity is a central concern in promoting Universal Health Coverage (UHC), the impact of social exclusion on equity in UHC remains underexplored. This paper examines challenges faced by socially excluded populations, with an emphasis on Indigenous peoples, to receive UHC in Latin America. We argue that social exclusion can have negative effects on health systems and can undermine progress towards UHC. We examine two case studies, one in Guatemala and one in Peru, involving citizen-led accountability initiatives that aim to identify and address problems with health care services for socially excluded groups. The case studies reveal how social exclusion can affect equity in UHC. METHODS: In-depth analysis was conducted of all peer reviewed articles published between 2015 and 2019 on the two cases (11 in total), and two non-peer reviewed reports published over the same period. In addition, two of the three authors contributed their first-hand knowledge gathered through practitioner involvement with the citizen-led initiatives examined in the two cases. The analysis sought to identify and compare challenges faced by socially excluded Indigenous populations to receive UHC in the two cases. RESULTS: Citizen-led accountability initiatives in Guatemala and Peru reveal very similar patterns of serious deficiencies that undermine efforts towards the realization of Universal Health Coverage in both countries. In each case, the socially excluded populations are served by a dysfunctional publicly provided health system marked by gaps and often invisible barriers. The cases suggest that, while funding and social rights to coverage have expanded, marginalized populations in Guatemala and Peru still do not receive either the health care services or the protection against financial hardship promised by health systems in each country. In both cases, the dysfunctional character of the system remains in place, undermining progress towards UHC. CONCLUSIONS: We conclude that efforts to promote UHC cannot stop at increasing health systems financing. In addition, these efforts need to contend with the deeper challenges of democratizing state institutions, including health systems, involved in marginalizing and excluding certain population groups. This includes stronger accountability systems within public institutions. More inclusive accountability mechanisms are an important step in promoting equitable progress towards UHC.

Building collective power in citizen-led initiatives for health accountability in Guatemala: the role of networks.

BACKGROUND: Citizen-led accountability initiatives are a critical strategy for redressing the causes of health inequalities and promoting better health system governance. A growing body of evidence points to the need for putting power relations at the forefront of understanding and operationalizing citizen-led accountability, rather than technical tools and best practices. In this study, we apply a network lens to the question of how initiatives build collective power to redress health system failures affecting marginalized communities in three municipalities in Guatemala. METHODS: Network mapping and interpretive discussions were used to examine relational qualities of citizen-led initiatives' networks and explore the resources they offer for mobilizing action and influencing health accountability. Participants in the municipal-level initiatives responded to a social network analysis questionnaire focused on their ties of communication and collaboration with other initiative participants and their interactions with authorities regarding health system problems. Discussions with participants about the maps generated enriched our view of what the ties represented and their history of collective action and also provided space for planning action to strengthen their networks. RESULTS: Our findings indicate that network qualities like cohesiveness and centralization reflected the initiative participants' agency in adapting to their sociopolitical context, and participants' social positions were a key resource in providing connection to a broad base of support for mobilizing collective action to document health service deficiencies and advocate for solutions. Their legitimacy as "representatives of the people" enabled them to engage with authorities from a bolstered position of power, and their iterative interactions with authorities further contributed to develop their advocacy capabilities and resulted in accountability gains. CONCLUSIONS: Our study provided evidence to counter the tendency to underestimate the assets and capabilities that marginalized citizens have for building power, and affirmed the idea that best-fit, with-the-grain approaches are well-suited for highly unequal settings characterized by weak governance. Efforts to support and understand change processes in citizen-led initiatives should include focus on adaptive network building to enable contextually-embedded approaches that leverage the collective power of the users of health services and grassroots leaders on the frontlines of accountability.

Engaging with complexity to improve the health of indigenous people: a call for the use of systems thinking to tackle health inequity.

The 400 million indigenous people worldwide represent a wealth of linguistic and cultural diversity, as well as traditional knowledge and sustainable practices that are invaluable resources for human development. However, indigenous people remain on the margins of society in high, middle and low-income countries, and they bear a disproportionate burden of poverty, disease, and mortality compared to the general population. These inequalities have persisted, and in some countries have even worsened, despite the overall improvements in health indicators in relation to the 15-year push to meet the Millennium Development Goals. As we enter the Sustainable Development Goals (SDGs) era, there is growing consensus that efforts to achieve Universal Health Coverage (UHC) and promote sustainable development should be guided by the moral imperative to improve equity. To achieve this, we need to move beyond the reductionist tendency to frame indigenous health as a problem of poor health indicators to be solved through targeted service delivery tactics and move towards holistic, integrated approaches that address the causes of inequalities both inside and outside the health sector. To meet the challenge of engaging with the conditions underlying inequalities and promoting transformational change, equity-oriented research and practice in the field of indigenous health requires: engaging power, context-adapted strategies to improve service delivery, and mobilizing networks of collective action. The application of systems thinking approaches offers a pathway for the evolution of equity-oriented research and practice in collaborative, politically informed and mutually enhancing efforts to understand and transform the systems that generate and reproduce inequities in indigenous health. These approaches hold the potential to strengthen practice through the development of more nuanced, context-sensitive strategies for redressing power imbalances, reshaping the service delivery environment and fostering the dynamics of collective action for political reform.

Abuse and discrimination towards indigenous people in public health care facilities: experiences from rural Guatemala.

BACKGROUND: Health inequalities disproportionally affect indigenous people in Guatemala. Previous studies have noted that the disadvantageous situation of indigenous people is the result of complex and structural elements such as social exclusion, racism and discrimination. These elements need to be addressed in order to tackle the social determinants of health. This research was part of a larger participatory collaboration between Centro de Estudios para la Equidad y Gobernanza en los Servicios de Salud (CEGSS) and community based organizations aiming to implement social accountability in rural indigenous municipalities of Guatemala. Discrimination while seeking health care services in public facilities was ranked among the top three problems by communities and that should be addressed in the social accountability intervention. This study aimed to understand and categorize the episodes of discrimination as reported by indigenous communities. METHODS: A participatory approach was used, involving CEGSS's researchers and field staff and community leaders. One focus group in one rural village of 13 different municipalities was implemented. Focus groups were aimed at identifying instances of mistreatment in health care services and documenting the account of those who were affected or who witnessed them. All of the 132 obtained episodes were transcribed and scrutinized using a thematic analysis. RESULTS: Episodes described by participants ranged from indifference to violence (psychological, symbolic, and physical), including coercion, mockery, deception and racism. Different expressions of discrimination and mistreatment associated to poverty, language barriers, gender, ethnicity and social class were narrated by participants. CONCLUSIONS: Addressing mistreatment in public health settings will involve tackling the prevalent forms of discrimination, including racism. This will likely require profound, complex and sustained interventions at the programmatic and policy levels beyond the strict realm of public health services. Future studies should assess the magnitude of the occurrence of episodes of maltreatment and racism within indigenous areas and also explore the providers' perceptions about the problem.

Posting and transfer: key to fostering trust in government health services.

Appropriate deployment or posting and transfer (P&T) of health workers - placing the right people in the right positions at the right time - lies at the heart of fostering communities' faith in government health services and cementing the role of the health system as a core social institution. The authors of this paper have been involved in an ongoing transnational dialogue about P&T practices and determinants. This dialogue seeks to call attention to the importance of P&T as a health system function; to urge donors and policy-makers working in health systems, HRH and public administration governance to consider how to address issues around P&T; and to suggest avenues and approaches to research. P&T is a vexed and unresolved issue in many low- and middle-income countries that requires, above all, political commitment to improving public sector services and to new thinking and research. It holds promise as a focal point for inter-disciplinary collaboration in research and implementation that can inform other areas in HRH and health systems strengthening. Innovative social science and management theorizing, and iterative, locally driven interventions that focus on establishing transparent professional norms and building the credibility of government administration, including the health services, are likely the way forward.

Making the post-MDG global health goals relevant for highly inequitable societies: findings from a consultation with marginalized populations in Guatemala.

INTRODUCTION: The United Nations presented a set of Millennium Development Goals that aimed to improve social and economic development and eradicate poverty by 2015. Most low and middle-income countries will not meet these goals and today there is a need to set new development agenda, especially when it comes to health. The paper presents the findings from a community consultation process carried out within the Goals and Governance for Global Health (GO4Health) research consortium in Guatemala, which aims to identify community needs and expectations around public policies and health services. METHODS: Through a participative and open consultation process with experts, civil society organizations and members of the research team, the municipalities of Tectitan and Santa Maria Nebaj were selected. A community consultation process was undertaken with community members and community leaders. Group discussions and in-depth interviews were conducted and later analyzed using thematic analysis, a qualitative method that can be used to analyze data in a way that allows for the identification of recurrent patterns that can be grouped into categories and themes, was used. FINDINGS: Following the Go4Health framework's domains for understanding health-related needs, the five themes identified were health, social determinants of health, essential health needs and their provision, roles and responsibilities of relevant stakeholders and community participation in decision-making. Participants reported high levels of discrimination related to ethnicity, to being poor and to living in rural areas. Ethnicity played a major role in how community members feel they are cared for in the health system. CONCLUSION: Achieving health goals in a context of deep-rooted inequality and marginalization requires going beyond the simple expansion of health services and working with developing trusting relationships between health service providers and community members. Involving community members in decision-making processes that shape policies will contribute to a larger process of community empowerment and democratization. Still, findings from the region show that tackling these issues may prove complicated and require going beyond the health system, as this lack of trust and discrimination has permeated to all public policies that deal with indigenous and rural populations.

'History obligates us to do it': political capabilities of Indigenous grassroots leaders of health accountability initiatives in rural Guatemala.

Growing interest in how marginalised citizens can leverage countervailing power to make health systems more inclusive and equitable points to the need for politicised frameworks for examining bottom-up accountability initiatives. This study explores how political capabilities are manifested in the actions and strategies of Indigenous grassroots leaders of health accountability initiatives in rural Guatemala. Qualitative data were gathered through group discussions and interviews with initiative leaders (called defenders of the right to health) and initiative collaborators in three municipalities. Analysis was oriented by three dimensions of political capabilities proposed for evaluating the longer-term value of participatory development initiatives: political learning, reshaping networks and patterns of representation. Our findings indicated that the defenders' political learning began with actionable knowledge about defending the right to health and citizen participation. The defenders used their understanding of local norms to build trust with remote Indigenous communities and influence them to participate in monitoring to attempt to hold the state accountable for the discriminatory and deficient healthcare they received. Network reshaping was focused on broadening their base of support. Their leadership strategies enabled them to work with other grassroots leaders and access resources that would expand their reach in collective action and lend them more influence representing their problems beyond the local level. Patterns of representing their interests with a range of local and regional authorities indicated they had gained confidence and credibility through their evolving capability to navigate the political landscape and seek the right authority based on the situation. Our results affirm the critical importance of sustained, long-term processes of engagement with marginalised communities and representatives of the state to enable grassroots leaders of accountability initiatives to develop the capabilities needed to mobilise collective action, shift the terms of interaction with the state and build more equitable health systems.

Challenges with pediatric surgical financing and universal health coverage in Guatemala: A qualitative analysis.

The financing of surgical care for children in low- and middle-income countries (LMICs) remains challenging and may restrict adherence to universal health coverage (UHC) frameworks. Our aims were to describe Guatemala's national pediatric surgical financing structure, to identify financing challenges, and to develop recommendations to improve the financing of surgical care for children. We conducted a qualitative study of the financing of surgical care for children in Guatemala's public health system with key informant interviews (n = 20) with experts in the medical, financial, and political health sectors. We used this data to generate recommendations to improve surgical care financing for children. We identified several systemic challenges to the financing of surgical care for children, including passive purchasing structures, complex political contexts, health system fragmentation, widespread use of informal fees for surgical services, and lack of earmarked funding for surgical care. Patient and provider challenges include lack of provider input in non-personnel funding decisions, and patients functioning as both financing agents and beneficiaries in the same financing stream. Key recommendations include reducing health finance system fragmentation through resource pooling, increasing earmarked funding for surgical care with quantifiable outcome measures, engagement with clinical providers in non-personnel budgetary decision-making, and use of innovative financing instruments such as resource pooling. Surgical financing for children in Guatemala requires substantial remodeling to increase access to timely, affordable, and safe surgical care and improve alignment with Guatemala's UHC scheme.

Rapamycin limits CD4+ T cell proliferation in simian immunodeficiency virus-infected rhesus macaques on antiretroviral therapy.

Proliferation of latently infected CD4+ T cells with replication-competent proviruses is an important mechanism contributing to HIV persistence during antiretroviral therapy (ART). One approach to targeting this latent cell expansion is to inhibit mTOR, a regulatory kinase involved with cell growth, metabolism, and proliferation. Here, we determined the effects of chronic mTOR inhibition with rapamycin with or without T cell activation in SIV-infected rhesus macaques (RMs) on ART. Rapamycin perturbed the expression of multiple genes and signaling pathways important for cellular proliferation and substantially decreased the frequency of proliferating CD4+ memory T cells (TM cells) in blood and tissues. However, levels of cell-associated SIV DNA and SIV RNA were not markedly different between rapamycin-treated RMs and controls during ART. T cell activation with an anti-CD3LALA antibody induced increases in SIV RNA in plasma of RMs on rapamycin, consistent with SIV production. However, upon ART cessation, both rapamycin and CD3LALA-treated and control-treated RMs rebounded in less than 12 days, with no difference in the time to viral rebound or post-ART viral load set points. These results indicate that, while rapamycin can decrease the proliferation of CD4+ TM cells, chronic mTOR inhibition alone or in combination with T cell activation was not sufficient to disrupt the stability of the SIV reservoir.

Rapid assessment of the performance of malaria control strategies implemented by countries in the Amazon subregion using adequacy criteria: case study.

BACKGROUND: The objective of this study was to implement a rapid assessment of the performance of four malaria control strategies (indoor spraying, insecticide-treated bed nets, timely diagnosis, and artemisinin-based combination therapy) using adequacy criteria. The assessment was carried out in five countries of the Amazon subregion (Bolivia, Colombia, Ecuador, Guyana, and Peru). METHODS: A list of criteria in three areas was created for each of the four strategies: preliminary research that supports the design and adaptation of the control strategies, coverage of the control strategies and quality of the implementation of the strategies. The criteria were selected by the research team and based on the technical guidelines established by the World Health Organization. Each criterion included in the four lists was graded relative to whether evidence exists that the criterion is satisfied (value 1), not satisfied (value 0) or partially satisfied (value 0.5). The values obtained were added and reported according to a scale of three implementation categories: adequate, intermediate and deficient. RESULTS: Implementation of residual indoor spraying and timely diagnosis was adequate in one country and intermediate or deficient in the rest. Insecticide-treated bed nets ranged between deficient and intermediate in all the countries, while implementation of artemisinin-based combination therapy (ACT) was adequate in three countries and intermediate in the other two countries evaluated. CONCLUSIONS: Although ACT is the strategy with the better implementation in all countries, major gaps exist in implementation of the other three malaria control strategies in terms of technical criteria, coverage and quality desired. The countries must implement action plans to close the gaps in the various criteria and thereby improve the performance of the interventions. The assessment tools developed, based on adequacy criteria, are considered useful for a rapid assessment by malaria control authorities in the different countries.

Measuring the Impact of Targeting FcRn-Mediated IgG Recycling on Donor-Specific Alloantibodies in a Sensitized NHP Model.

Background: In transplantation, plasmapheresis and IVIg provide the mainstay of treatment directed at reducing or removing circulating donor-specific antibody (DSA), yet both have limitations. We sought to test the efficacy of targeting the IgG recycling mechanism of the neonatal Fc receptor (FcRn) using anti-FcRn mAb therapy in a sensitized non-human primate (NHP) model, as a pharmacological means of lowering DSA. Methods: Six (6) rhesus macaque monkeys, previously sensitized by skin transplantation, received a single dose of 30mg/kg anti-RhFcRn IV, and effects on total IgG, as well as DSA IgG, were measured, in addition to IgM and protective immunity. Subsequently, 60mg/kg IV was given in the setting of kidney transplantation from skin graft donors. Kidney transplant recipients received RhATG, and tacrolimus, MMF, and steroid for maintenance immunosuppression. Results: Circulating total IgG was reduced from a baseline 100% on D0 to 32.0% (mean, SD ± 10.6) on d4 post infusion (p<0.05), while using a DSA assay. T-cell flow cross match (TFXM) was reduced to 40.6±12.5% of baseline, and B-cell FXCM to 52.2±19.3%. Circulating total IgM and DSA IgM were unaffected by treatment. Pathogen-specific antibodies (anti-gB and anti-tetanus toxin IgG) were significantly reduced for 14d post infusion. Post-transplant, circulating IgG responded to anti-FcRn mAb treatment, but DSA increased rapidly. Conclusion: Targeting the FcRn-mediated recycling of IgG is an effective means of lowering circulating donor-specific IgG in the sensitized recipient, although in the setting of organ transplantation mechanisms of rapid antibody rise post-transplant remains unaffected.

Non-neutralizing Antibodies May Contribute to Suppression of SIVmac239 Viremia in Indian Rhesus Macaques.

The antiviral properties of broadly neutralizing antibodies against HIV are well-documented but no vaccine is currently able to elicit protective titers of these responses in primates. While current vaccine modalities can readily induce non-neutralizing antibodies against simian immunodeficiency virus (SIV) and HIV, the ability of these responses to restrict lentivirus transmission and replication remains controversial. Here, we investigated the antiviral properties of non-neutralizing antibodies in a group of Indian rhesus macaques (RMs) that were vaccinated with vif, rev, tat, nef, and env, as part of a previous study conducted by our group. These animals manifested rapid and durable control of viral replication to below detection limits shortly after SIVmac239 infection. Although these animals had no serological neutralizing activity against SIVmac239 prior to infection, their pre-challenge titers of Env-binding antibodies correlated with control of viral replication. To assess the contribution of anti-Env humoral immune responses to virologic control in two of these animals, we transiently depleted their circulating antibodies via extracorporeal plasma immunoadsorption and inhibition of IgG recycling through antibody-mediated blockade of the neonatal Fc receptor. These procedures reduced Ig serum concentrations by up to 80% and temporarily induced SIVmac239 replication in these animals. Next, we transferred purified total Ig from the rapid controllers into six vaccinated RMs one day before intrarectal challenge with SIVmac239. Although recipients of the hyperimmune anti-SIV Ig fraction were not protected from infection, their peak and chronic phase viral loads were significantly lower than those in concurrent unvaccinated control animals. Together, our results suggest that non-neutralizing Abs may play a role in the suppression of SIVmac239 viremia.

Global Health in the Age of COVID-19: Responsive Health Systems Through a Right to Health Fund.

We propose that a Right to Health Capacity Fund (R2HCF) be created as a central institution of a reimagined global health architecture developed in the aftermath of the COVID-19 pandemic. Such a fund would help ensure the strong health systems required to prevent disease outbreaks from becoming devastating global pandemics, while ensuring genuinely universal health coverage that would encompass even the most marginalized populations. The R2HCF's mission would be to promote inclusive participation, equality, and accountability for advancing the right to health. The fund would focus its resources on civil society organizations, supporting their advocacy and strengthening mechanisms for accountability and participation. We propose an initial annual target of US$500 million for the fund, adjusted based on needs assessments. Such a financing level would be both achievable and transformative, given the limited right to health funding presently and the demonstrated potential of right to health initiatives to strengthen health systems and meet the health needs of marginalized populations-and enable these populations to be treated with dignity. We call for a civil society-led multi-stakeholder process to further conceptualize, and then launch, an R2HCF, helping create a world where, whether during a health emergency or in ordinary times, no one is left behind.

Social participation within a context of political violence: implications for the promotion and exercise of the right to health in Guatemala.

Social participation has been understood in many different ways, and there are even typologies classifying participation by the degree of a population's control in decision making. Participation can vary from a symbolic act, which does not involve decision making, to processes in which it constitutes the principal tool for redistributing power within a population. This article argues that analyzing social participation from a perspective of power relations requires knowledge of the historical, social, and economic processes that have characterized the social relations in a specific context. Applying such an analysis to Guatemala reveals asymmetrical power relations characterized by a long history of repression and political violence. The armed conflict during the second half of the 20th century had devastating consequences for a large portion of the population as well as the country's social leadership. The ongoing violence resulted in negative psychosocial effects among the population, including mistrust toward institutions and low levels of social and political participation. Although Guatemala made progress in creating spaces for social participation in public policy after signing the Peace Accords in 1996, the country still faces after-effects of the conflict. One important task for the organizations that work in the field of health and the right to health is to help regenerate the social fabric and to rebuild trust between the state and its citizens. Such regeneration involves helping the population gain the skills, knowledge, and information needed in order to participate in and affect formal political processes that are decided and promoted by various public entities, such as the legislative and executive branches, municipal governments, and political parties. This process also applies to other groups that build citizenship through participation, such as neighborhood organizations and school and health committees.

Reach and effectiveness of a HEARTS hypertension pilot project in Guatemala / Cobertura y efectividad de un proyecto piloto HEARTS para el control de la hipertensión en Guatemala / Alcance e efetividade de um projeto piloto de controle da hipertensão arterial da iniciativa HEARTS na Guatemala

[ABSTRACT]. The World Health Organization Global Hearts initiative (HEARTS) and technical package aim to improve the primary health care management of hypertension and other risk factors for cardiovascular disease at the population level. This study describes the first HEARTS implementation pilot project in Guatemala’s Ministry of Health (MOH) primary health care system. This pilot began in April 2022 in six primary health care facilities in three rural indigenous municipalities. The project consisted of HEARTS-aligned strategies adapted to enhance program sustainability in Guatemala. Outcomes were defined using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. The primary reach outcome was treatment count, defined as the absolute number of patients per month receiving medication treatment for hypertension. The primary effectiveness outcomes were mean systolic blood pressure (BP), mean diastolic BP, and proportion of patients with BP control (<130/80 mmHg). In the first month of the post-implementation period, there was a statistically significant increase of 25 patients treated per month above the baseline of 20 to 25 patients (P = .002), followed by a significant increase of 2.4 additional patients treated each month (P = .005) thereafter. The mean change in systolic BP was −4.4 (95% CI, −8.2 to −0.5; P = 0.028) mmHg, and the mean change in diastolic BP was −0.9 (95% CI, −2.8 to 1.1; P = .376) mmHg. The proportion of the cohort with BP control increased from 33.4% at baseline to 47.1% at 6 months (adjusted change, 13.7%; 95% CI, 2.2% to 25.2%; P = .027). These findings support the feasibility of implementing the HEARTS model for BP control throughout the MOH primary health care system, which is where most Guatemalans with hypertension seek care.

[RESUMEN]. El paquete técnico de la Iniciativa Global Hearts ("HEARTS") de la Organización Mundial de la Salud tiene como objetivo mejorar el control de la hipertensión y de otros factores de riesgo de enfermedades cardiovasculares a nivel poblacional en el ámbito de la atención primaria de salud de salud. Este estudio describe el primer proyecto piloto de implementación de HEARTS en el sistema de atención primaria de salud del Ministerio de Salud de Guatemala. El proyecto, que comenzó en abril del 2022 en seis centros de atención primaria de salud pertenecientes a tres municipios rurales indígenas, consistió en estrategias alineadas con HEARTS y adaptadas para mejorar la sostenibilidad del programa en Guatemala. Los criterios de valoración de los resultados se definieron mediante el marco estandarizado de evaluación de cobertura, efectividad, adopción, implementación y mantenimiento (RE-AIM, por su sigla en inglés). El criterio principal de la cobertura fue la cantidad de tratamientos, definida como el número absoluto de pacientes por mes que recibían tratamiento farmacológico para la hipertensión. Los criterios principales de la efectividad fueron la media de presión arterial (PA) sistólica, la media de PA diastólica y la proporción de pacientes con un control de la PA (<130/80 mmHg). En el primer mes del período posterior a la implementación, se registró un aumento estadísticamente significativo de 25 pacientes tratados al mes por encima del valor inicial de 20 a 25 pacientes (n = 25; p = 0,002), seguido de un aumento significativo de 2,4 pacientes adicionales tratados al mes (p = 0,005) posteriormente. El cambio en la media de la PA sistólica fue de -4,4 (IC del 95%: -8,2 a -0,5); p = 0,028) mmHg, en tanto que el cambio en la media de la PA diastólica fue de -0,9 (IC del 95%, -2,8 a 1,1); p = 0,376) mmHg. La proporción de la cohorte con control de la PA aumentó del 33,4% al inicio al 47,1% a los seis meses (cambio ajustado, 13,7%; IC del 95%, 2,2% a 25,2%; p = 0,027). Estos resultados respaldan la viabilidad de la implementación del modelo HEARTS para el control de la PA en la totalidad del sistema de atención primaria de salud del Ministerio de Salud de Guatemala, al que acude en busca de atención la mayoría de las personas con hipertensión.

[RESUMO]. O pacote de medidas técnicas da iniciativa Global Hearts (“HEARTS”) da Organização Mundial da Saúde tem como objetivo melhorar o controle da hipertensão arterial e de outros fatores de risco para doenças cardiovasculares na atenção primária à saúde em nível populacional. Este estudo descreve o primeiro projeto-piloto de implementação da iniciativa HEARTS no sistema de atenção primária à saúde do Ministério da Saúde da Guatemala. O projeto-piloto começou em abril de 2022 em seis estabelecimentos de atenção primária à saúde em três municípios indígenas rurais. O projeto consistiu em estratégias alinhadas à iniciativa HEARTS e adaptadas para melhorar a sustentabilidade do programa na Guatemala. Os desfechos foram definidos usando a estrutura de avaliação RE-AIM (sigla em inglês para alcance, efetividade, adoção, implementação e manutenção). O desfecho primário de alcance foi a quantidade de tratamentos, definida como o número absoluto de pacientes por mês que receberam tratamento medicamentoso para hipertensão. Os desfechos primários de efetividade foram pressão arterial (PA) sistólica média, PA diastólica média e proporção de pacientes com controle da PA (<130/80 mmHg). No primeiro mês do período pós-implementação, houve um aumento estatisticamente significante de 25 pacientes tratados por mês acima da linha de base de 20 a 25 pacientes (n = 25; P = 0,002), seguido de um aumento significante de 2,4 pacientes adicionais tratados a cada mês (P = 0,005) depois disso. A mudança média na PA sistólica foi de −4,4 (intervalo de confiança [IC] de 95%: −8,2 a −0,5; P = 0,028) mmHg, e a mudança média na PA diastólica foi de −0,9 (IC de 95%: −2,8 a 1,1; P = 0,376) mmHg. A proporção da coorte com controle da PA aumentou de 33,4% na linha de base para 47,1% após 6 meses (mudança ajustada, 13,7%; IC de 95%: 2,2% a 25,2%; P = 0,027). Esses achados apoiam a viabilidade da implementação do modelo HEARTS para o controle da PA em todo o sistema de atenção primária à saúde do Ministério da Saúde da Guatemala, no qual a maioria dos indivíduos com hipertensão arterial procura atendimento.