Adjuvant-dependent effects on the safety and efficacy of inactivated SARS-CoV-2 vaccines during heterologous infection by a SARS-related coronavirus.

Inactivated whole virus SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide (Alum) are among the most widely used COVID-19 vaccines globally and have been critical to the COVID-19 pandemic response. Although these vaccines are protective against homologous virus infection in healthy recipients, the emergence of novel SARS-CoV-2 variants and the presence of large zoonotic reservoirs provide significant opportunities for vaccine breakthrough, which raises the risk of adverse outcomes including vaccine-associated enhanced respiratory disease (VAERD). To evaluate this possibility, we tested the performance of an inactivated SARS-CoV-2 vaccine (iCoV2) in combination with Alum against either homologous or heterologous coronavirus challenge in a mouse model of coronavirus-induced pulmonary disease. Consistent with human results, iCoV2 + Alum protected against homologous challenge. However, challenge with a heterologous SARS-related coronavirus, Rs-SHC014-CoV (SHC014), up to at least 10 months post-vaccination, resulted in VAERD in iCoV2 + Alum-vaccinated animals, characterized by pulmonary eosinophilic infiltrates, enhanced pulmonary pathology, delayed viral clearance, and decreased pulmonary function. In contrast, vaccination with iCoV2 in combination with an alternative adjuvant (RIBI) did not induce VAERD and promoted enhanced SHC014 clearance. Further characterization of iCoV2 + Alum-induced immunity suggested that CD4+ T cells were a major driver of VAERD, and these responses were partially reversed by re-boosting with recombinant Spike protein + RIBI adjuvant. These results highlight potential risks associated with vaccine breakthrough in recipients of Alum-adjuvanted inactivated vaccines and provide important insights into factors affecting both the safety and efficacy of coronavirus vaccines in the face of heterologous virus infections.

Targeting spike glycans to inhibit SARS-CoV2 viral entry.

SARS-CoV-2 spike harbors glycans which function as ligands for lectins. Therefore, it should be possible to exploit lectins to target SARS-CoV-2 and inhibit cellular entry by binding glycans on the spike protein. Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. Here, we show that BOA binds to the spike protein and is a potent inhibitor of SARS-CoV-2 viral entry at nanomolar concentrations. Using a variety of biophysical approaches, we demonstrate that the interaction is avidity driven and that BOA cross-links the spike protein into soluble aggregates. Furthermore, using virus neutralization assays, we demonstrate that BOA effectively inhibits all tested variants of concern as well as SARS-CoV 2003, establishing that multivalent glycan-targeting molecules have the potential to act as pan-coronavirus inhibitors.

Overestimation of school-based deworming coverage resulting from school-based reporting.

BACKGROUND: Soil Transmitted Helminths (STH) infect over 1.5 billion people globally and are associated with anemia and stunting, resulting in an annual toll of 1.9 million Disability-Adjusted Life Years (DALYs). School-based deworming (SBD), via mass drug administration (MDA) campaigns with albendazole or mebendazole, has been recommended by the World Health Organization to reduce levels of morbidity due to STH in endemic areas. DeWorm3 is a cluster-randomized trial, conducted in three study sites in Benin, India, and Malawi, designed to assess the feasibility of interrupting STH transmission with community-wide MDA as a potential strategy to replace SBD. This analysis examines data from the DeWorm3 trial to quantify discrepancies between school-level reporting of SBD and gold standard individual-level survey reporting of SBD. METHODOLOGY/PRINCIPAL FINDINGS: Population-weighted averages of school-level SBD calculated at the cluster level were compared to aggregated individual-level SBD estimates to produce a Mean Squared Error (MSE) estimate for each study site. In order to estimate individual-level SBD coverage, these MSE values were applied to SBD estimates from the control arm of the DeWorm3 trial, where only school-level reporting of SBD coverage had been collected. In each study site, SBD coverage in the school-level datasets was substantially higher than that obtained from individual-level datasets, indicating possible overestimation of school-level SBD coverage. When applying observed MSE to project expected coverages in the control arm, SBD coverage dropped from 89.1% to 70.5% (p-value < 0.001) in Benin, from 97.7% to 84.5% (p-value < 0.001) in India, and from 41.5% to 37.5% (p-value < 0.001) in Malawi. CONCLUSIONS/SIGNIFICANCE: These estimates indicate that school-level SBD reporting is likely to significantly overestimate program coverage. These findings suggest that current SBD coverage estimates derived from school-based program data may substantially overestimate true pediatric deworming coverage within targeted communities. TRIAL REGISTRATION: NCT03014167.

A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines.

Continuous evolution of SARS-CoV-2 alters the antigenicity of the immunodominant spike (S) receptor-binding domain and N-terminal domain, undermining the efficacy of vaccines and monoclonal antibody therapies. To overcome this challenge, we set out to develop a vaccine focusing antibody responses on the highly conserved but metastable S2 subunit, which folds as a spring-loaded fusion machinery. Here, we describe a protein design strategy enabling prefusion-stabilization of the SARS-CoV-2 S2 subunit and high yield recombinant expression of trimers with native structure and antigenicity. We demonstrate that our design strategy is broadly generalizable to all sarbecoviruses, as exemplified with the SARS-CoV-1 (clade 1a) and PRD-0038 (clade 3) S2 fusion machineries. Immunization of mice with a prefusion-stabilized SARS-CoV-2 S2 trimer vaccine elicits broadly reactive sarbecovirus antibody responses and neutralizing antibody titers of comparable magnitude against Wuhan-Hu-1 and the immune evasive XBB.1.5 variant. Vaccinated mice were protected from weight loss and disease upon challenge with SARS-CoV-2 XBB.1.5, providing proof-of-principle for fusion machinery sarbecovirus vaccines motivating future development.

Impact of the Salud Mesoamerica Initiative on delivery care choices in Guatemala, Honduras, and Nicaragua.

BACKGROUND: The Salud Mesoamérica Initiative (SMI) is a public-private collaboration aimed to improve maternal and child health conditions in the poorest populations of Mesoamerica through a results-based aid mechanism. We assess the impact of SMI on the staffing and availability of equipment and supplies for delivery care, the proportion of institutional deliveries, and the proportion of women who choose a facility other than the one closest to their locality of residence for delivery. METHODS: We used a quasi-experimental design, including baseline and follow-up measurements between 2013 and 2018 in intervention and comparison areas of Guatemala, Nicaragua, and Honduras. We collected information on 8754 births linked to the health facility closest to the mother's locality of residence and the facility where the delivery took place (if attended in a health facility). We fit difference-in-difference models, adjusting for women's characteristics (age, parity, education), household characteristics, exposure to health promotion interventions, health facility level, and country. RESULTS: Equipment, inputs, and staffing of facilities improved after the Initiative in both intervention and comparison areas. After adjustment for covariates, institutional delivery increased between baseline and follow-up by 3.1 percentage points (ß = 0.031, 95% CI -0.03, 0.09) more in intervention areas than in comparison areas. The proportion of women in intervention areas who chose a facility other than their closest one to attend the delivery decreased between baseline and follow-up by 13 percentage points (ß = - 0.130, 95% CI -0.23, - 0.03) more than in the comparison group. CONCLUSIONS: Results indicate that women in intervention areas of SMI are more likely to go to their closest facility to attend delivery after the Initiative has improved facilities' capacity, suggesting that results-based aid initiatives targeting poor populations, like SMI, can increase the use of facilities closest to the place of residence for delivery care services. This should be considered in the design of interventions after the COVID-19 pandemic may have changed health and social conditions.

Protective Efficacy of Rhesus Adenovirus COVID-19 Vaccines against Mouse-Adapted SARS-CoV-2.

The global COVID-19 pandemic has sparked intense interest in the rapid development of vaccines as well as animal models to evaluate vaccine candidates and to define immune correlates of protection. We recently reported a mouse-adapted SARS-CoV-2 virus strain (MA10) with the potential to infect wild-type laboratory mice, driving high levels of viral replication in respiratory tract tissues as well as severe clinical and respiratory symptoms, aspects of COVID-19 disease in humans that are important to capture in model systems. We evaluated the immunogenicity and protective efficacy of novel rhesus adenovirus serotype 52 (RhAd52) vaccines against MA10 challenge in mice. Baseline seroprevalence is lower for rhesus adenovirus vectors than for human or chimpanzee adenovirus vectors, making these vectors attractive candidates for vaccine development. We observed that RhAd52 vaccines elicited robust binding and neutralizing antibody titers, which inversely correlated with viral replication after challenge. These data support the development of RhAd52 vaccines and the use of the MA10 challenge virus to screen novel vaccine candidates and to study the immunologic mechanisms that underscore protection from SARS-CoV-2 challenge in wild-type mice. IMPORTANCE We have developed a series of SARS-CoV-2 vaccines using rhesus adenovirus serotype 52 (RhAd52) vectors, which exhibit a lower seroprevalence than human and chimpanzee vectors, supporting their development as novel vaccine vectors or as an alternative adenovirus (Ad) vector for boosting. We sought to test these vaccines using a recently reported mouse-adapted SARS-CoV-2 (MA10) virus to (i) evaluate the protective efficacy of RhAd52 vaccines and (ii) further characterize this mouse-adapted challenge model and probe immune correlates of protection. We demonstrate that RhAd52 vaccines elicit robust SARS-CoV-2-specific antibody responses and protect against clinical disease and viral replication in the lungs. Further, binding and neutralizing antibody titers correlated with protective efficacy. These data validate the MA10 mouse model as a useful tool to screen and study novel vaccine candidates, as well as the development of RhAd52 vaccines for COVID-19.

Protective efficacy of rhesus adenovirus COVID-19 vaccines against mouse-adapted SARS-CoV-2.

The global COVID-19 pandemic has sparked intense interest in the rapid development of vaccines as well as animal models to evaluate vaccine candidates and to define immune correlates of protection. We recently reported a mouse-adapted SARS-CoV-2 virus strain (MA10) with the potential to infect wild-type laboratory mice, driving high levels of viral replication in respiratory tract tissues as well as severe clinical and respiratory symptoms, aspects of COVID-19 disease in humans that are important to capture in model systems. We evaluated the immunogenicity and protective efficacy of novel rhesus adenovirus serotype 52 (RhAd52) vaccines against MA10 challenge in mice. Baseline seroprevalence is lower for rhesus adenovirus vectors than for human or chimpanzee adenovirus vectors, making these vectors attractive candidates for vaccine development. We observed that RhAd52 vaccines elicited robust binding and neutralizing antibody titers, which inversely correlated with viral replication after challenge. These data support the development of RhAd52 vaccines and the use of the MA10 challenge virus to screen novel vaccine candidates and to study the immunologic mechanisms that underscore protection from SARS-CoV-2 challenge in wild-type mice. IMPORTANCE: We have developed a series of SARS-CoV-2 vaccines using rhesus adenovirus serotype 52 (RhAd52) vectors, which exhibits a lower seroprevalence than human and chimpanzee vectors, supporting their development as novel vaccine vectors or as an alternative Ad vector for boosting. We sought to test these vaccines using a recently reported mouse-adapted SARS-CoV-2 (MA10) virus to i) evaluate the protective efficacy of RhAd52 vaccines and ii) further characterize this mouse-adapted challenge model and probe immune correlates of protection. We demonstrate RhAd52 vaccines elicit robust SARS-CoV-2-specific antibody responses and protect against clinical disease and viral replication in the lungs. Further, binding and neutralizing antibody titers correlated with protective efficacy. These data validate the MA10 mouse model as a useful tool to screen and study novel vaccine candidates, as well as the development of RhAd52 vaccines for COVID-19.

A broadly neutralizing antibody protects against SARS-CoV, pre-emergent bat CoVs, and SARS-CoV-2 variants in mice.

SARS-CoV in 2003, SARS-CoV-2 in 2019, and SARS-CoV-2 variants of concern (VOC) can cause deadly infections, underlining the importance of developing broadly effective countermeasures against Group 2B Sarbecoviruses, which could be key in the rapid prevention and mitigation of future zoonotic events. Here, we demonstrate the neutralization of SARS-CoV, bat CoVs WIV-1 and RsSHC014, and SARS-CoV-2 variants D614G, B.1.1.7, B.1.429, B1.351 by a receptor-binding domain (RBD)-specific antibody DH1047. Prophylactic and therapeutic treatment with DH1047 demonstrated protection against SARS-CoV, WIV-1, RsSHC014, and SARS-CoV-2 B1.351infection in mice. Binding and structural analysis showed high affinity binding of DH1047 to an epitope that is highly conserved among Sarbecoviruses. We conclude that DH1047 is a broadly neutralizing and protective antibody that can prevent infection and mitigate outbreaks caused by SARS-like strains and SARS-CoV-2 variants. Our results argue that the RBD conserved epitope bound by DH1047 is a rational target for pan Group 2B coronavirus vaccines.

Prevention and therapy of SARS-CoV-2 and the B.1.351 variant in mice.

Improving the standard of clinical care for individuals infected with SARS-CoV-2 variants is a global health priority. Small molecule antivirals like remdesivir (RDV) and biologics such as human monoclonal antibodies (mAb) have demonstrated therapeutic efficacy against SARS-CoV-2, the causative agent of COVID-19. However, it is not known if combination RDV/mAb will improve outcomes over single agent therapies or whether antibody therapies will remain efficacious against variants. In kinetic studies in a mouse-adapted model of ancestral SARS-CoV-2 pathogenesis, we show that a combination of two mAbs in clinical trials, C144 and C135, have potent antiviral effects against even when initiated 48 hours after infection. The same antibody combination was also effective in prevention and therapy against the B.1.351 variant of concern (VOC). Combining RDV and antibodies provided a modest improvement in outcomes compared to single agents. These data support the continued use of RDV to treat SARS-CoV-2 infections and support the continued clinical development of the C144 and C135 antibody combination to treat patients infected with SARS-CoV-2 variants.

A Newcastle disease virus (NDV) expressing membrane-anchored spike as a cost-effective inactivated SARS-CoV-2 vaccine.

A successful SARS-CoV-2 vaccine must be not only safe and protective but must also meet the demand on a global scale at low cost. Using the current influenza virus vaccine production capacity to manufacture an egg-based inactivated Newcastle disease virus (NDV)/SARS-CoV-2 vaccine would meet that challenge. Here, we report pre-clinical evaluations of an inactivated NDV chimera stably expressing the membrane-anchored form of the spike (NDV-S) as a potent COVID-19 vaccine in mice and hamsters. The inactivated NDV-S vaccine was immunogenic, inducing strong binding and/or neutralizing antibodies in both animal models. More importantly, the inactivated NDV-S vaccine protected animals from SARS-CoV-2 infections or significantly attenuated SARS-CoV-2 induced disease. In the presence of an adjuvant, antigen-sparing could be achieved, which would further reduce the cost while maintaining the protective efficacy of the vaccine.

Access and use of oxytocin for postpartum haemorrhage prevention: a pre-post study targeting the poorest in six Mesoamerican countries.

OBJECTIVES: Haemorrhage remains the leading cause of maternal mortality in Central America. The Salud Mesoamérica Initiative aims to reduce such mortality via performance indicators. Our objective was to assess the availability and administration of oxytocin, before and after applying Salud Mesoamérica Initiative interventions in the poorest health facilities across Central America. DESIGN: Pre-post study. SETTING: 166 basic-level and comprehensive-level health facilities in Belize, Guatemala, Honduras, Mexico, Nicaragua and Panama. PARTICIPANTS: A random sample of medical records for uncomplicated full-term deliveries (n=2470) per International Classification of Diseases coding at baseline (July 2011 to August 2013) and at first-phase follow-up (January 2014 to October 2014). INTERVENTIONS: A year of intervention implementation prior to first-phase follow-up data collection focused on improving access to oxytocin by strengthening supply chains, procurement, storage practices and pharmacy inventory monitoring, using a results-based financing model. PRIMARY AND SECONDARY OUTCOME MEASURES: Oxytocin availability (primary outcome) and administration (secondary outcome) for postpartum haemorrhage prevention. RESULTS: Availability of oxytocin increased from 82.9% to 97.6%. Oxytocin administration increased from 83.6% to 88.4%. Significant improvements were seen for availability of oxytocin (adjusted OR (aOR)=8.41, 95% CI 1.50 to 47.30). Administration of oxytocin was found to be significantly higher in Honduras (aOR=2.96; 95% CI 1.00 to 8.76) in reference to Guatemala at follow-up. CONCLUSION: After interventions to increase health facility supplies, the study showed a significant improvement in availability but not administration of oxytocin in poor communities within Mesoamerica. Efforts are needed to improve the use of oxytocin.

Antenatal care as a means to increase participation in the continuum of maternal and child healthcare: an analysis of the poorest regions of four Mesoamérican countries.

BACKGROUND: Antenatal care (ANC) is a means to identify high-risk pregnancies and educate women so that they might experience a healthier delivery and outcome. There is a lack of evidence about whether receipt of ANC is an effective strategy for keeping women in the system so they partake in other maternal and child interventions, particularly for poor women. The present analysis examines whether ANC uptake is associated with other maternal and child health behaviors in poor mothers in Guatemala, Honduras, Nicaragua, and Mexico (Chiapas). METHODS: We conducted a cross-sectional survey of women regarding their uptake of ANC for their most recent delivery in the last two years and their uptake of selected services and healthy behaviors along a continuity of maternal and child healthcare. We conducted logistic regressions on a sample of 4844 births, controlling for demographic, household, and maternal characteristics to understand the relationship between uptake of ANC and later participation in the continuum of care. RESULTS: Uptake of four ANC visits varied by country from 17.0% uptake in Guatemala to 81.4% in Nicaragua. In all countries but Nicaragua, ANC was significantly associated with in-facility delivery (IFD) (Guatemala odds ratio [OR] = 5.28 [95% confidence interval [CI] 3.62-7.69]; Mexico OR = 5.00 [95% CI: 3.41-7.32]; Honduras OR = 2.60 [95% CI: 1.42-4.78]) and postnatal care (Guatemala OR = 4.82 [95% CI: 3.21-7.23]; Mexico OR = 4.02 [95% CI: 2.77-5.82]; Honduras OR = 2.14 [95% CI: 1.26-3.64]), but did not appear to have any positive relationship with exclusive breastfeeding habits or family planning methods, which may be more strongly determined by cultural influences. CONCLUSIONS: Our results demonstrate that uptake of the WHO-recommended four ANC visits has limited effectiveness on uptake of services in some poor populations in Mesoamérica. Our study highlights the need for continued and varied efforts in these populations to increase both the uptake and the effectiveness of ANC in encouraging positive and lasting effects on women's uptake of health care services.

Methods to measure quality of care and quality indicators through health facility surveys in low- and middle-income countries.

OBJECTIVE: Present methods to measure standardized, replicable and comparable metrics to measure quality of medical care in low- and middle-income countries. DESIGN: We constructed quality indicators for maternal, neonatal and child care. To minimize reviewer judgment, we transformed criteria from check-lists into data points and decisions into conditional algorithms. Distinct criteria were established for each facility level and type of care. Indicators were linked to discharge diagnoses. We designed electronic abstraction tools using computer-assisted personal interviewing software. SETTING: We present results for data collected in the poorest areas of Belize, Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua, Panama and the state of Chiapas in Mexico (January-October 2014). RESULTS: We collected data from 12 662 medical records. Indicators show variations of quality of care between and within countries. Routine interventions, such as quality antenatal care (ANC), immediate neonatal care and postpartum contraception, had low levels of compliance. Records that complied with quality ANC ranged from 68.8% [confidence interval (CI):64.5-72.9] in Costa Rica to 5.7% [CI:4.0-8.0] in Guatemala. Less than 25% of obstetric and neonatal complications were managed according to standards in all countries. CONCLUSIONS: Our study underscores that, with adequate resources and technical expertise, collecting data for quality indicators at scale in low- and middle-income countries is possible. Our indicators offer a comparable, replicable and standardized framework to identify variations on quality of care. The indicators and methods described are highly transferable and could be used to measure quality of care in other countries.

Results-based aid with lasting effects: sustainability in the Salud Mesoamérica Initiative.

BACKGROUND: The Salud Mesoamérica Initiative is a public-private partnership aimed at reducing maternal and child morbidity and mortality for the poorest populations in Central America and the southernmost state of Mexico. Currently at the midpoint of implementation and with external funding expected to phase out by 2020, SMI's sustainability warrants evaluation. In this study, we examine if the major SMI components fit into the Dynamic Sustainability Framework to predict whether SMI benefits could be sustainable beyond the external funding and to identify threats to sustainability. METHODS: Through the 2016 Salud Mesoamérica Initiative Process Evaluation, we applied qualitative methods including document review, key informant interviews, focus group discussions, and a social network analysis to address our objective. RESULTS: SMI's design continuously evolves and aligns with national needs and objectives. Partnerships, the regional approach, and the results-based aid model create a culture that prioritizes health care. SMI's sector-wide approach and knowledge-sharing framework strengthen health systems. Evidence-based practice promotes policy dialogue and scale-up of interventions. CONCLUSION: Most SMI elements fit within the Dynamic Sustainability Framework, suggesting a likelihood of sustainability after external funding ceases, and subsequent application of lessons learned by the global community. This includes a flexible design, partnerships and a culture of prioritizing healthcare, health systems strengthening mechanisms, policy changes, and scale-ups of interventions. However, threats to sustainability, including possible transient culture of prioritizing health care, dissipation of reputational risk and financial partnerships, and personnel turnover, need to be addressed.

Appropriate and timely antibiotic administration for neonatal sepsis in Mesoamérica.

Neonatal sepsis is a leading cause of mortality among children under-5 in Latin America. The Salud Mesoamérica Initiative (SMI), a multicountry results-based aid programme, was designed to improve maternal, newborn and child health in impoverished communities in Mesoamérica. This study examines the delivery of timely and appropriate antibiotics for neonatal sepsis among facilities participating in the SMI project. A multifaceted health facility survey was implemented at SMI inception and approximately 18 months later as a follow-up. A random sample of medical records from neonates diagnosed with sepsis was reviewed, and data regarding antibiotic administration were extracted. In this paper, we present the percentage of patients who received timely (within 2 hours) and appropriate antibiotics. Multilevel logistic regression was used to assess for potential facility-level determinants of timely and appropriate antibiotic treatment. Among 821 neonates diagnosed with sepsis in 63 facilities, 61.8% received an appropriate antibiotic regimen, most commonly ampicillin plus an aminoglycoside. Within 2 hours of presentation, 32.3% received any antibiotic and only 26.6% received an appropriate regimen within that time. Antibiotic availability improved over the course of the SMI project, increasing from 27.5% at baseline to 64.0% at follow-up, and it was highly correlated with timely and appropriate antibiotic administration (adjusted OR=5.36, 95% CI 2.85 to 10.08). However, we also found a decline in the percentage of neonates documented to have received appropriate antibiotics (74.4% vs 51.1%). Our study demonstrated early success of the SMI project through improvements in the availability of appropriate antibiotic regimens for neonatal sepsis. At the same time, overall rates of timely and appropriate antibiotic administration remain low, and the next phase of the initiative will need to address other barriers to the provision of life-saving antibiotic treatment for neonatal sepsis.

Supply-side interventions to improve health: Findings from the Salud Mesoamérica Initiative.

BACKGROUND: Results-based aid (RBA) is increasingly used to incentivize action in health. In Mesoamerica, the region consisting of southern Mexico and Central America, the RBA project known as the Salud Mesoamérica Initiative (SMI) was designed to target disparities in maternal and child health, focusing on the poorest 20% of the population across the region. METHODS AND FINDINGS: Data were first collected in 365 intervention health facilities to establish a baseline of indicators. For the first follow-up measure, 18 to 24 months later, 368 facilities were evaluated in these same areas. At both stages, we measured a near-identical set of supply-side performance indicators in line with country-specific priorities in maternal and child health. All countries showed progress in performance indicators, although with different levels. El Salvador, Honduras, Nicaragua, and Panama reached their 18-month targets, while the State of Chiapas in Mexico, Guatemala, and Belize did not. A second follow-up measurement in Chiapas and Guatemala showed continued progress, as they achieved previously missed targets nine to 12 months later, after implementing a performance improvement plan. CONCLUSIONS: Our findings show an initial success in the supply-side indicators of SMI. Our data suggest that the RBA approach can be a motivator to improve availability of drugs and services in poor areas. Moreover, our innovative monitoring and evaluation framework will allow health officials with limited resources to identify and target areas of greatest need.

Health system strategies to increase HIV screening among pregnant women in Mesoamerica.

BACKGROUND: To propose health system strategies to meeting the World Health Organization (WHO) recommendations on HIV screening through antenatal care (ANC) services, we assessed predictors of HIV screening, and simulated the impact of changes in these predictors on the probability of HIV screening in Guatemala, Honduras, Mexico (State of Chiapas), Nicaragua, Panama, and El Salvador. METHODS: We interviewed a representative sample of women of reproductive age from the poorest Mesoamerican areas on ANC services, including HIV screening. We used a multivariate logistic regression model to examine correlates of HIV screening. First differences in expected probabilities of HIV screening were simulated for health system correlates that were associated with HIV screening. RESULTS: Overall, 40.7% of women were screened for HIV during their last pregnancy through ANC. This rate was highest in El Salvador and lowest in Guatemala. The probability of HIV screening increased with education, household expenditure, the number of ANC visits, and the type of health care attendant of ANC visits. If all women were to be attended by a nurse, or a physician, and were to receive at least four ANC visits, the probability of HIV screening would increase by 12.5% to reach 45.8%. CONCLUSIONS: To meet WHO's recommendations for HIV screening, special attention should be given to the poorest and least educated women to ensure health equity and progress toward an HIV-free generation. In parallel, health systems should be strengthened in terms of testing and human resources to ensure that every pregnant woman gets screened for HIV. A 12.5% increase in HIV screening would require a minimum of four ANC visits and an appropriate professional attendance of these visits.

Perceptions of and barriers to family planning services in the poorest regions of Chiapas, Mexico: a qualitative study of men, women, and adolescents.

BACKGROUND: In the poorest regions of Chiapas, Mexico, 50.2% of women in need of contraceptives do not use any modern method. A qualitative study was needed to design effective and culturally appropriate interventions. METHODS: We used purposive maximum-variation sampling to select eight municipalities with a high proportion of residents in the poorest wealth quintile, including urban, rural, indigenous, and non-indigenous communities. We conducted 44 focus group discussions with 292 women, adolescent women, and men using semi-structured topic guides. We analyzed the data through recursive abstraction. RESULTS: There were intergenerational and cultural gaps in the acceptability of family planning, and in some communities family planning use was greatly limited by gender roles and religious objections to contraception. Men strongly influenced family planning choices in many households, but were largely unreached by outreach and education programs due to their work hours. Respondents were aware of many modern methods but often lacked deeper knowledge and held misconceptions about long-term fertility risks posed by some hormonal methods. Acute physical side effects also dissuaded use. The implant was a new and highly acceptable method due to ease of use, low upkeep, and minimal side effects; however, it was perceived as subject to stock-outs. Adolescent women reported being refused services at health facilities and requested more reproductive health information from their parents and schools. Mass and social media are growing sources of reproductive health information. CONCLUSIONS: Our study identifies a number of barriers to family planning that have yet to be adequately addressed by existing programs in Chiapas' poorest regions, and calls for reinvigorated efforts to provide effective, acceptable, and culturally appropriate interventions for these communities.

Healthy competition drives success in results-based aid: Lessons from the Salud Mesoamérica Initiative.

OBJECTIVES: The Salud Mesoamérica Initiative (SMI) is a three-operation strategy, and is a pioneer in the world of results-based aid (RBA) in terms of the success it has achieved in improving health system inputs following its initial operation. This success in meeting pre-defined targets is rare in the world of financial assistance for health. We investigated the influential aspects of SMI that could have contributed to its effectiveness in improving health systems, with the aim of providing international donors, bilateral organizations, philanthropies, and recipient countries with new perspectives that can help increase the effectiveness of future assistance for health, specifically in the arena of RBA. METHODS: Qualitative methods based on the criteria of relevance and effectiveness proposed by the Development Assistance Committee of the Organization for Economic Co-operation and Development. Our methods included document review, key informant interviews, a focus group discussion, and a partnership analysis. PARTICIPANTS: A purposive sample of 113 key informants, comprising donors, representatives from the Inter-American Development Bank, ministries of health, technical assistance organizations, evaluation organizations, and health care providers. RESULTS: During May-October 2016, we interviewed regarding the relevance and effectiveness of SMI. Themes emerged relative to the topics we investigated, and covered the design and the drivers of success of the initiative. The success is due to 1) the initiative's regional approach, which pressured recipient countries to compete toward meeting targets, 2) a robust and flexible design that incorporated the richness of input from stakeholders at all levels, 3) the design-embedded evaluation component that created a culture of accountability among recipient countries, and 4) the reflective knowledge environment that created a culture of evidence-based decision-making. CONCLUSIONS: A regional approach involving all appropriate stakeholders, and based on knowledge sharing and embedded evaluation can help ensure the effectiveness of future results-based aid programs for health in global settings.

Barriers and facilitators for institutional delivery among poor Mesoamerican women: a cross-sectional study.

Professional skilled care has shown to be one of the most promising strategies to reduce maternal mortality, and in-facility deliveries are a cost-effective way to ensure safe births. Countries in Mesoamerica have emphasized in-facility delivery care by professionally skilled attendants, but access to good-quality delivery care is still lacking for many women. We examined the characteristics of women who had a delivery in a health facility and determinants of the decision to bypass a closer facility and travel to a distant one. We used baseline information from the Salud Mesoamerica Initiative (SMI). Data were collected from a large household and facilities sample in the poorest quintile of the population in Guatemala, Honduras and Nicaragua. The analysis included 1592 deliveries. After controlling for characteristics of women and health facilities, being primiparous (RR = 1.15, 95% CI 1.10, 1.21), being literate (RR = 1.24, 95% CI 1.04, 1.48), having antenatal care (RR = 1.68, 95% CI 1.24, 2.27), being informed of the need for having a C-section (RR = 1.07, 95% CI 1.02, 1.11) and travel time to the closest facility totaling 1-2 h vs under 30 min (RR = 0.88, 95% CI 0.77, 0.99) were associated with in-health facility deliveries. In Guatemala, increased availability of medications and equipment at a distant facility was strongly associated with bypassing the closest facility in favor of a distant one for delivery (RR = 2.10, 95% CI 1.08, 4.07). Our study showed a strong correlation between well-equipped facilities and delivery attendance in poor areas of Mesoamerica. Indeed, women were more likely to travel to more distant facilities if the facilities were of higher level, which scored higher on our capacity score. Our findings call for improving the capacity of health facilities, quality of care and addressing cultural and accessibility barriers to increase institutional delivery among the poor population in Mesoamerica.