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.

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.

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.

Coverage and timing of antenatal care among poor women in 6 Mesoamerican countries.

BACKGROUND: Poor women in the developing world have a heightened need for antenatal care (ANC) but are often the least likely to attend it. This study examines factors associated with the number and timing of ANC visits for poor women in Guatemala, Honduras, Mexico, Nicaragua, Panama, and El Salvador. METHODS: We surveyed 8366 women regarding the ANC they attended for their most recent birth in the past two years. We conducted logistic regressions to examine demographic, household, and health characteristics associated with attending at least one skilled ANC visit, four skilled visits, and a skilled visit in the first trimester. RESULTS: Across countries, 78 % of women attended at least one skilled ANC visit, 62 % attended at least four skilled visits, and 56 % attended a skilled visit in the first trimester. The proportion of women attending four skilled visits was highest in Nicaragua (81 %) and lowest in Guatemala (18 %) and Panama (38 %). In multiple countries, women who were unmarried, less-educated, adolescent, indigenous, had not wanted to conceive, and lacked media exposure were less likely to meet international ANC guidelines. In countries with health insurance programs, coverage was associated with attending skilled ANC, but not the timeliness. CONCLUSIONS: Despite significant policy reforms and initiatives targeting the poor, many women living in the poorest regions of Mesoamérica are not meeting ANC guidelines. Both supply and demand interventions are needed to prioritize vulnerable groups, reduce unplanned pregnancies, and reach populations not exposed to common forms of media. Top performing municipalities can inform effective practices across the region.

Institutional Delivery and Satisfaction among Indigenous and Poor Women in Guatemala, Mexico, and Panama.

Indigenous women in Mesoamerica experience disproportionately high maternal mortality rates and are less likely to have institutional deliveries. Identifying correlates of institutional delivery, and satisfaction with institutional deliveries, may help improve facility utilization and health outcomes in this population. We used baseline surveys from the Salud Mesoamérica Initiative to analyze data from 10,895 indigenous and non-indigenous women in Guatemala and Mexico (Chiapas State) and indigenous women in Panama. We created multivariable Poisson regression models for indigenous (Guatemala, Mexico, Panama) and non-indigenous (Guatemala, Mexico) women to identify correlates of institutional delivery and satisfaction. Compared to their non-indigenous peers, indigenous women were substantially less likely to have an institutional delivery (15.2% vs. 41.5% in Guatemala (P<0.001), 29.1% vs. 73.9% in Mexico (P<0.001), and 70.3% among indigenous Panamanian women). Indigenous women who had at least one antenatal care visit were more than 90% more likely to have an institutional delivery (adjusted risk ratio (aRR) = 1.94, 95% confidence interval (CI): 1.44-2.61), compared to those who had no visits. Indigenous women who were advised to give birth in a health facility (aRR = 1.46, 95% CI: 1.18-1.81), primiparous (aRR = 1.44, 95% CI: 1.24-1.68), informed that she should have a Caesarean section (aRR = 1.41, 95% CI: 1.21-1.63), and had a secondary or higher level of education (aRR = 1.36, 95% CI: 1.04-1.79) also had substantially higher likelihoods of institutional delivery. Satisfaction among indigenous women was associated with being able to be accompanied by a community health worker (aRR = 1.15, 95% CI: 1.05-1.26) and facility staff speaking an indigenous language (aRR = 1.10, 95% CI: 1.02-1.19). Additional effort should be exerted to increase utilization of birthing facilities by indigenous and poor women in the region. Improving access to antenatal care and opportunities for higher-level education may increase institutional delivery rates, and providing culturally adapted services may improve satisfaction.

Diarrhea Prevalence, Care, and Risk Factors Among Poor Children Under 5 Years of Age in Mesoamerica.

Care practices and risk factors for diarrhea among impoverished communities across Mesoamerica are unknown. Using Salud Mesoamérica Initiative baseline data, collected 2011-2013, we assessed the prevalence of diarrhea, adherence to evidence-based treatment guidelines, and potential diarrhea correlates in poor and indigenous communities across Mesoamerica. This study surveyed 14,500 children under 5 years of age in poor areas of El Salvador, Guatemala, Mexico (Chiapas State), Nicaragua, and Panama. We compared diarrhea prevalence and treatment modalities using χ(2) tests and used multivariable Poisson regression models to calculate adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) for potential correlates of diarrhea. The 2-week point prevalence of diarrhea was 13% overall, with significant differences between countries (P < 0.05). Approximately one-third of diarrheal children were given oral rehydration solution and less than 3% were given zinc. Approximately 18% were given much less to drink than usual or nothing to drink at all. Antimotility medication was given to 17% of diarrheal children, while antibiotics were inappropriately given to 36%. In a multivariable regression model, compared with children 0-5 months, those 6-23 months had a 49% increased risk for diarrhea (aRR = 1.49, 95% CI = 1.15, 1.95). Our results call for programs to examine and remedy low adherence to evidence-based treatment guidelines.

Health and wealth in Mesoamerica: findings from Salud Mesomérica 2015.

BACKGROUND: Individual income and poverty are associated with poor health outcomes. The poor face unique challenges related to access, education, financial capacity, environmental effects, and other factors that threaten their health outcomes. METHODS: We examined the variation in the health outcomes and health behaviors among the poorest quintile in eight countries of Mesoamerica using data from the Salud Mesomérica 2015 baseline household surveys. We used multivariable logistic regression to measure the association between delivering a child in a health facility and select household and maternal characteristics, including education and measures of wealth. RESULTS: Health indicators varied greatly between geographic segments. Controlling for other demographic characteristics, women with at least secondary education were more likely to have an in-facility delivery compared to women who had not attended school (OR: 3.20, 95 % confidence interval [CI]: 2.56-3.99, respectively). Similarly, women from households with the highest expenditure were more likely to deliver in a health facility compared to those from the lowest expenditure households (OR 3.06, 95 % CI: 2.43-3.85). Household assets did not impact these associations. Moreover, we found that commonly-used definitions of poverty do not align with the disparities in health outcomes observed in these communities. CONCLUSIONS: Although poverty measured by expenditure or wealth is associated with health disparities or health outcomes, a composite indicator of health poverty based on coverage is more likely to focus attention on health problems and solutions. Our findings call for the public health community to define poverty by health coverage measures rather than income or wealth. Such a health-poverty metric is more likely to generate attention and mobilize targeted action by the health communities than our current definition of poverty.

Salud Mesoamérica 2015 Initiative: design, implementation, and baseline findings.

BACKGROUND: Health has improved markedly in Mesoamerica, the region consisting of southern Mexico and Central America, over the past decade. Despite this progress, there remain substantial inequalities in health outcomes, access, and quality of medical care between and within countries. Poor, indigenous, and rural populations have considerably worse health indicators than national or regional averages. In an effort to address these health inequalities, the Salud Mesoamérica 2015 Initiative (SM2015), a results-based financing initiative, was established. METHODS: For each of the eight participating countries, health targets were set to measure the progress of improvements in maternal and child health produced by the Initiative. To establish a baseline, we conducted censuses of 90,000 households, completed 20,225 household interviews, and surveyed 479 health facilities in the poorest areas of Mesoamerica. Pairing health facility and household surveys allows us to link barriers to care and health outcomes with health system infrastructure components and quality of health services. RESULTS: Indicators varied significantly within and between countries. Anemia was most prevalent in Panama and least prevalent in Honduras. Anemia varied by age, with the highest levels observed among children aged 0 to 11 months in all settings. Belize had the highest proportion of institutional deliveries (99%), while Guatemala had the lowest (24%). The proportion of women with four antenatal care visits with a skilled attendant was highest in El Salvador (90%) and the lowest in Guatemala (20%). Availability of contraceptives also varied. The availability of condoms ranged from 83% in Nicaragua to 97% in Honduras. Oral contraceptive pills and injectable contraceptives were available in just 75% of facilities in Panama. IUDs were observed in only 21.5% of facilities surveyed in El Salvador. CONCLUSIONS: These data provide a baseline of much-needed information for evidence-based action on health throughout Mesoamerica. Our baseline estimates reflect large disparities in health indicators within and between countries and will facilitate the evaluation of interventions and investments deployed in the region over the next three to five years. SM2015's innovative monitoring and evaluation framework will allow health officials with limited resources to identify and target areas of greatest need.