HIV Diagnostics and Vaccines: It Takes Two to Tango.

Current serological tests for HIV screening and confirmation of infection present challenges to the adoption of HIV vaccines. The detection of vaccine-induced HIV-1 antibodies in the absence of HIV-1 infection, referred to as vaccine-induced seropositivity/seroreactivity, confounds the interpretation of test results, causing misclassification of HIV-1 status with potential affiliated stigmatization. For HIV vaccines to be widely adopted with high community confidence and uptake, tests that are agnostic to vaccination status (i.e., only positive for true HIV-1 infection) of tested individuals are needed. Successful development and deployment of such tests will require HIV vaccine developers to work in concert with diagnostic developers. Such tests will need to match today's high-performance standards (accuracy, cost-effectiveness, simplicity) for use in both vaccinated and unvaccinated populations, especially in low- and middle-income countries with high HIV burden. Herein, we discuss the challenges and strategies for developing modified serological HIV tests for concurrent deployment with HIV vaccines.

Cross-country analysis of contextual factors and implementation strategies in under-5 mortality reduction in six low- and middle-income countries 2000-2015.

BACKGROUND: The Exemplars in Under-5 Mortality (U5M) was a multiple cases study of how six low- and middle-income countries (LMICs), Bangladesh, Ethiopia, Nepal, Peru, Rwanda, and Senegal, implemented health system-delivered evidence-based interventions (EBIs) to reduce U5M between 2000 and 2015 more effectively than others in their regions or with similar economic growth. Using implementation research, we conducted a cross-country analysis to compare decision-making pathways for how these countries chose, implemented, and adapted strategies for health system-delivered EBIs that mitigated or leveraged contextual factors to improve implementation outcomes in reducing amenable U5M. METHODS: The cross-country analysis was based on the hybrid mixed methods implementation research framework used to inform the country case studies. The framework included a common pathway of Exploration, Preparation, Implementation, Adaptation, and Sustainment (EPIAS). From the existing case studies, we extracted contextual factors which were barriers, facilitators, or determinants of strategic decisions; strategies to implement EBIs; and implementation outcomes including acceptability and coverage. We identified common factors and strategies shared by countries, and individual approaches used by countries reflecting differences in contextual factors and goals. RESULTS: We found the six countries implemented many of the same EBIs, often using similar strategies with adaptations to local context and disease burden. Common implementation strategies included use of data by decision-makers to identify problems and prioritize EBIs, determine implementation strategies and their adaptation, and measure outcomes; leveraging existing primary healthcare systems; and community and stakeholder engagement. We also found common facilitators included culture of donor and partner coordination and culture and capacity of data use, while common barriers included geography and culture and beliefs. We found evidence for achieving implementation outcomes in many countries and EBIs including acceptability, coverage, equity, and sustainability. DISCUSSION: We found all six countries used a common pathway to implementation with a number of strategies common across EBIs and countries which contributed to progress, either despite contextual barriers or by leveraging facilitators. The transferable knowledge from this cross-country study can be used by other countries to more effectively implement EBIs known to reduce amenable U5M and contribute to strengthening health system delivery now and in the future.

Inequity in the face of success: understanding geographic and wealth-based equity in success of facility-based delivery for under-5 mortality reduction in six countries.

BACKGROUND: Between 2000-2015, many low- and middle-income countries (LMICs) implemented evidence-based interventions (EBIs) known to reduce under-5 mortality (U5M). Even among LMICs successful in reducing U5M, this drop was unequal subnationally, with varying success in EBI implementation. Building on mixed methods multi-case studies of six LMICs (Bangladesh, Ethiopia, Nepal, Peru, Rwanda, and Senegal) leading in U5M reduction, we describe geographic and wealth-based equity in facility-based delivery (FBD), a critical EBI to reduce neonatal mortality which requires a trusted and functional health system, and compare the implementation strategies and contextual factors which influenced success or challenges within and across the countries. METHODS: To obtain equity gaps in FBD coverage and changes in absolute geographic and wealth-based equity between 2000-2015, we calculated the difference between the highest and lowest FBD coverage across subnational regions and in the FBD coverage between the richest and poorest wealth quintiles. We extracted and compared contextual factors and implementation strategies associated with reduced or remaining inequities from the country case studies. RESULTS: The absolute geographic and wealth-based equity gaps decreased in three countries, with greatest drops in Rwanda - decreasing from 50 to 5% across subnational regions and from 43 to 13% across wealth quintiles. The largest increases were seen in Bangladesh - from 10 to 32% across geography - and in Ethiopia - from 22 to 58% across wealth quintiles. Facilitators to reducing equity gaps across the six countries included leadership commitment and culture of data use; in some countries, community or maternal and child health insurance was also an important factor (Rwanda and Peru). Barriers across all the countries included geography, while country-specific barriers included low female empowerment subnationally (Bangladesh) and cultural beliefs (Ethiopia). Successful strategies included building on community health worker (CHW) programs, with country-specific adaptation of pre-existing CHW programs (Rwanda, Ethiopia, and Senegal) and cultural adaptation of delivery protocols (Peru). Reducing delivery costs was successful in Senegal, and partially successful in Nepal and Ethiopia. CONCLUSION: Variable success in reducing inequity in FBD coverage among countries successful in reducing U5M underscores the importance of measuring not just coverage but also equity. Learning from FBD interventions shows the need to prioritize equity in access and uptake of EBIs for the poor and in remote areas by adapting the strategies to local context.

Lessons from Peru to reduce under-5 mortality: understanding program implementation and context.

BACKGROUND: Health policymakers aiming to reduce under-5 mortality (U5M) often lack data regarding how successful interventions in other countries were implemented. The Exemplars in U5M Study identified countries that achieved significant reductions in amenable U5M. This case study in Peru used implementation research to explore the contextual factors and strategies that contributed to the successful implementation of key evidence-based interventions (EBIs). METHODS: This research utilized a hybrid implementation research framework and a mixed-methods approach to understand the factors associated with EBI implementation and the successful reduction of U5M between 2000-2015. A desk review of existing literature on EBIs and U5M in Peru was completed, and in-depth interviews were performed with key Peruvian informants to understand the implementation strategies employed and the contextual factors that facilitated or were barriers to success. For the purposes of this analysis, three EBIs were selected and evaluated: antenatal care visits (ANC), facility-based deliveries, and infant vaccination. RESULTS: Between 2000-2015, the percent of mothers attending at least four antenatal care visits rose from 69% to 96.9%, and the percent of facility-based deliveries increased from 56 to 91%. Three doses of the tetanus/diphtheria/pertussis vaccine, widely acknowledged as a key global health indicator, reached 90% by 2015. Key informants noted that economic growth, financial reforms, strong national commitment to reduce poverty in Peru, and national prioritization of maternal and child health, were important contextual factors that contributed to the successful reduction of U5M. They noted key strategies that helped achieve success during the implementation of EBIs, including utilization of data for decision-making, adaptation driven by cultural sensitivity to address gaps in coverage, and a focus on equity and anti-poverty initiatives with the participation of government, civil society, and political parties to assure continuity of policies. CONCLUSION: Several EBIs contributed to the successful reduction of U5M in Peru between 2000-2015. Strategies such as the focus on equity throughout the study period contributed to an increase in coverage of EBIs like ANC visits, facility-based deliveries and infant vaccination which worked to reduce U5M. Understanding how Peru successfully implemented programs that reduced preventable infant and child deaths could be useful to replicating this substantial public health success in other low- and middle-income countries.

Inequalities in health system coverage and quality: a cross-sectional survey of four Latin American countries.

The premise of health as a human right in Latin America has been challenged by health system fragmentation, quality gaps, a growing burden of chronic disease, sociopolitical upheaval, and the COVID-19 pandemic. We characterised inequities in health system quality in Colombia, Mexico, Peru, and Uruguay. We did a cross-sectional telephone survey with up to 1250 adults in each country. We created binary outcomes in coverage, user experience, system competence, and confidence in the system and calculated the slope index of inequality by income and education. Although access to care was high, only a third of respondents reported having a high-quality source of care and 25% of those with mental health needs had those needs met. Two-thirds of adults were able to access relevant preventive care and 42% of older adults were screened for cardiovascular disease. Telehealth access, communication and autonomy in most recent visit, reasonable waiting times, and receiving preventive health checks showed inequalities favouring people with a high income. In Uruguay, inequality between government and social security services explained a substantial proportion of disparities in preventive health access. In other study countries, inequalities were also substantial within government and social security subsectors. Essential health system functions are unequal in these four Latin American countries.

Population confidence in the health system in 15 countries: results from the first round of the People's Voice Survey.

Population confidence is essential to a well functioning health system. Using data from the People's Voice Survey-a novel population survey conducted in 15 low-income, middle-income, and high-income countries-we report health system confidence among the general population and analyse its associated factors. Across the 15 countries, fewer than half of respondents were health secure and reported being somewhat or very confident that they could get and afford good-quality care if very sick. Only a quarter of respondents endorsed their current health system, deeming it to work well with no need for major reform. The lowest support was in Peru, the UK, and Greece-countries experiencing substantial health system challenges. Wealthy, more educated, young, and female respondents were less likely to endorse the health system in many countries, portending future challenges for maintaining social solidarity for publicly financed health systems. In pooled analyses, the perceived quality of the public health system and government responsiveness to public input were strongly associated with all confidence measures. These results provide a post-COVID-19 pandemic baseline of public confidence in the health system. The survey should be repeated regularly to inform policy and improve health system accountability.

Programme science: a route to effective coverage and population-level impact for HIV and sexually transmitted infection prevention.

Improvements in context-specific programming are essential to address HIV and other sexually transmitted and blood-borne infection epidemics globally. A programme science approach emphasises the need for context-specific evidence and knowledge, generated on an ongoing basis, to inform timely and appropriate programmatic decisions. We aim to accelerate and improve the use of embedded research, inquiry, and learning to optimise population-level impact of public health programmes and to introduce an effective programme coverage framework as one tool to facilitate this goal. The framework was developed in partnership with public health experts in HIV and sexually transmitted and blood-borne infections through several workshops and meetings. The framework is a practice-based tool that centres on the use of data from iterative cycles of programme-embedded research and learning, as well as routine programme monitoring, to refine the strategy and implementation of a programme. This programme science approach aims to reduce programme coverage gaps, to optimise impact at the population level, and to achieve effective coverage. This framework should facilitate the generation of programme-embedded research and learning agendas to inform resource allocation, optimise population-level impact, and achieve equitable and effective programme coverage.

Rethinking how development assistance for health can catalyse progress on primary health care.

Global campaigns to control HIV, tuberculosis, malaria, and vaccine-preventable illnesses showed that large-scale impact can be achieved by using additional international financing to support selected, evidence-based, high-impact investment areas and to catalyse domestic resource mobilisation. Building on this paradigm, we make the case for targeting additional international funding for selected high-impact investments in primary health care. We have identified and costed a set of concrete, evidence-based investments that donors could support, which would be expected to have major impacts at an affordable cost. These investments are in: (1) individuals and communities empowered to engage in health decision making, (2) a new model of people-centred primary care, and (3) next generation community health workers. These three areas would be supported by strengthening two cross-cutting elements of national systems. The first is the digital tools and data that support facility, district, and national managers to improve processes, quality of care, and accountability across primary health care. The second is the educational, training, and supervisory systems needed to improve the quality of care. We estimate that with an additional international investment of between US$1·87 billion in a low-investment scenario and $3·85 billion in a high-investment scenario annually over the next 3 years, the international community could support the scale-up of this evidence-based package of investments in the 59 low-income and middle-income countries that are eligible for external financing from the World Bank Group's International Development Association.

Latin America and the Caribbean Code Against Cancer 1st Edition: 17 cancer prevention recommendations to the public and to policy-makers (World Code Against Cancer Framework).

Preventable risk factors are responsible of at least 40% of cases and almost 45% of all cancer deaths worldwide. Cancer is already the leading cause of death in almost half of the Latin American and the Caribbean countries constituting a public health problem. Cost-effective measures to reduce exposures through primary prevention and screening of certain types of cancers are critical in the fight against cancer but need to be tailored to the local needs and scenarios. The Latin America and the Caribbean (LAC) Code Against Cancer, 1st edition, consists of 17 evidence-based recommendations for the general public, based on the most recent solid evidence on lifestyle, environmental, occupational, and infectious risk factors, and medical interventions. Each recommendation is accompanied by recommendations for policymakers to guide governments establishing the infrastructure needed to enable the public adopting the recommendations. The LAC Code Against Cancer has been developed in a collaborative effort by a large number of experts from the region, under the umbrella strategy and authoritative methodology of the World Code Against Cancer Framework. The Code is a structured instrument ideal for cancer prevention and control that aims to raise awareness and educate the public, while building capacity and competencies to policymakers, health professionals, stakeholders, to contribute to reduce the burden of cancer in LAC.

Non-pharmaceutical interventions to combat COVID-19 in the Americas described through daily sub-national data.

This dataset covers national and subnational non-pharmaceutical interventions (NPI) to combat the COVID-19 pandemic in the Americas. Prior to the development of a vaccine, NPI were governments' primary tools to mitigate the spread of COVID-19. Variation in subnational responses to COVID-19 is high and is salient for health outcomes. This dataset captures governments' dynamic, varied NPI to combat COVID-19 for 80% of Latin America's population from each country's first case through December 2021. These daily data encompass all national and subnational units in Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Mexico, and Peru. The dataset includes individual and aggregate indices of nine NPI: school closures, work suspensions, public event cancellations, public transport suspensions, information campaigns, local travel restrictions, international travel controls, stay-at-home orders, and restrictions on the size of gatherings. We also collected data on mask mandates as a separate indicator. Local country-teams drew from multiple data sources, resulting in high-quality, reliable data. The dataset thus allows for consistent, meaningful comparisons of NPI within and across countries during the pandemic.

Mapping SARS-CoV-2 antigenic relationships and serological responses.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, multiple variants escaping preexisting immunity emerged, causing reinfections of previously exposed individuals. Here, we used antigenic cartography to analyze patterns of cross-reactivity among 21 variants and 15 groups of human sera obtained after primary infection with 10 different variants or after messenger RNA (mRNA)-1273 or mRNA-1273.351 vaccination. We found antigenic differences among pre-Omicron variants caused by substitutions at spike-protein positions 417, 452, 484, and 501. Quantifying changes in response breadth over time and with additional vaccine doses, our results show the largest increase between 4 weeks and >3 months after a second dose. We found changes in immunodominance of different spike regions, depending on the variant an individual was first exposed to, with implications for variant risk assessment and vaccine-strain selection.

Measuring people's views on health system performance: Design and development of the People's Voice Survey.

Todd Lewis and co-authors discuss development and use of the People's Voice Survey for health system assessment.

Diarrheal disease and associations with water access and sanitation in Indigenous Shawi children along the Armanayacu River basin in Peru.

INTRODUCTION: Diarrheal disease, particularly in children under 5 years old, remains a global health challenge due to its high prevalence and chronic health consequences. Public health interventions that reduce diarrheal disease risk include improving access to water, sanitation, and hygiene. Although Peru achieved the 2015 Millennium Development Goal (MDG) indicators for water access, less progress was achieved on sanitation. Furthermore, many Indigenous Peoples were overlooked in the MDG indicators, resulting in a prioritization of Indigenous Peoples in the 2030 Sustainable Development Goals (SDGs). This study aimed to estimate the prevalence of childhood diarrhea, characterize access to water and sanitation, and determine the association of childhood diarrhea with water access and sanitation indicators in 10 Shawi Indigenous communities along the Armanayacu River in the Peruvian Amazon. METHODS: A cross-sectional survey (n=82) that captured data on diarrheal disease, sociodemographic variables, and water and sanitation exposures was conducted in 10 Shawi communities. Nutritional status of children under 5 was also assessed via physical examination. Descriptive and comparative statistics were conducted. RESULTS: A small proportion (n=7; 8.54%) of participating children reported an episode of diarrhea in the previous month. Almost half (46.30%) of participating children had stunting, wasting, or both. Although not statistically significant, children living in households that used latrines were 4.29 times (95% confidence interval (CI) 1.01-18.19) more likely to report an episode of diarrhea than children living in households that practiced open defecation. Although not statistically significant, children living in households that used water treatment methods were 4.25 times (95%CI 0.54-33.71) more likely to report an episode of diarrhea than children living in households that did not. CONCLUSION: The prevalence of childhood diarrhea was lower for Shawi than for other Amazon areas. The higher prevalence of childhood diarrhea in households that used latrines and water treatments warrants further investigation into local risk and protective factors. These Shawi communities scored low for the WHO/UNICEF Joint Monitoring Programme indicators for water and sanitation, indicating that they should be prioritized in future water, sanitation, and hygiene initiatives. Research will be required to understand and incorporate local Indigenous values and cultural practices into water, sanitation, and hygiene initiatives to maximize intervention uptake and effectiveness.

Assessment of regional body composition, physical function and sarcopenia among peruvian women aging with HIV: A cross-sectional study.

Management of chronic conditions and optimization of overall health has become a primary global health concern in the care of people living with HIV in the era of highly active antiretroviral therapy (ART), particularly in lower-and-middle income countries where infrastructure for chronic disease management may be fragmented. Alterations in body composition can reflect important changes in musculoskeletal health, particularly among populations at risk for developing fat and muscle redistribution syndromes, such as women with HIV on ART. Given the lack of data on this topic in Latin America and the Caribbean, we designed an exploratory study to measure these outcomes in a population of women aging with HIV in Peru. We conducted a cross-sectional study among Peruvian women with and without HIV aged ≥40 years. Dual X-ray absorptiometry was used to measure trunk and limb lean mass (LM) and fat mass (FM). Physical performance was assessed with the Short Physical Performance Battery (SPPB) and physical strength with a dynamometer. Sarcopenia was assessed based upon EWGSOP criteria. We used linear regression to model associations between body composition, sarcopenia and physical performance scores. 104 women with HIV and 212 women without HIV were enrolled (mean age 52.4±8.2 vs. 56.4±8.8 years, p≤0.001). Among women with HIV, mean years since diagnosis was 11.8±6 and all were on ART. Mean SPPB score was 9.9 vs 10.8 (p<0.001) between both groups. Sarcopenia spectrum was found in 25.9% and 23.1%, respectively. In the multivariable regression analysis, trunk FM and older age were negatively correlated with physical performance among women with HIV. Severe sarcopenia was found among a greater proportion of those with HIV (3.8% vs. 0.9%, p = 0.84), however this finding was not statistically significant. Women with HIV had significantly lower SPPB scores compared to women without HIV, and trunk FM and upper limb LM were independent predictors for the SPPB and Grip Strength tests, respectively. Larger, prospective studies are needed in Latin America & the Caribbean to identify individuals at high risk for sarcopenia and declines in physical function, and to inform prevention guidelines.

Syphilis.

Syphilis is a sexually and vertically transmitted bacterial infection caused by the bacterium Treponema pallidum. Its prevalence is high in low-income and middle-income countries, and its incidence has increased in high-income countries in the last few decades among men who have sex with men. Syphilis is a major cause of adverse pregnancy outcomes in low-income and middle-income countries. Clinical features include a primary chancre at the point of inoculation, followed weeks later by the rash of secondary syphilis, a latent period, and in some cases, involvement of the eyes, CNS, and cardiovascular systems. It is diagnosed serologically. A single intramuscular dose of long-acting benzathine penicillin is recommended for people who have had syphilis for less than 1 year and longer courses for people with late latent syphilis. Control strategies include screening and treatment of all pregnant women, and targeted interventions for groups at high risk. Vaccine development, research on antibiotic prophylaxis, and digital messaging as prevention strategies are ongoing.

Prevalence of and risk factors for vertebral fracture and low bone mineral density among Peruvian women aging with HIV.

Osteoporosis and fracture risk among women with HIV in Latin America is understudied. In a sample of Peruvian women with and without HIV, women with HIV had lower femoral neck and total hip BMD and a higher proportion of vertebral fractures. Important treatment gaps were identified across both groups. PURPOSE: Studies have shown that patients with HIV are at increased risk for bone loss and fracture due to a combination of host, viral, and antiretroviral therapy (ART)-related factors. We aimed to explore the prevalence of vertebral fracture (VF) and low bone mineral density (BMD) among women aging with HIV in Peru and identify risk factors for osteoporosis and fracture in this population. METHODS: We enrolled women living with and without HIV aged ≥40 years between 2019 and 2020. Participants completed a survey and obtained dual X-ray absorptiometry (DXA) test to assess BMD at the lumbar spine (LS), femoral neck (FN), and total hip (TH). A subset of patients also obtained lateral thoracolumbar X-rays. Presence of VF was determined using the Genant semiquantitative method. Regression analyses were used to model associations between key risk factors and BMD. RESULTS: 104 women living with HIV and 212 women living without HIV were enrolled with a mean age of 52.4±8.2 and 56.4±8.8 years (p < 0.001). Among postmenopausal women (257/316, 81.3%), 26.3% of women living with HIV and 25.9% of those without HIV had osteoporosis. Among the 88 women living with HIV and 178 women living without HIV who obtained thoracolumbar X-rays, 12.5% and 6.2%, respectively, had at least one VF. Based on DXA and the FRAX score, 22/104 women living with HIV met criteria for osteoporosis treatment according to national guidelines; however, none were on treatment. Propensity score matching revealed that women living with HIV had 0.032 g/cm2 lower FN BMD (p = 0.012) and 0.034 g/cm2 lower TH BMD (p = 0.041) compared to women without HIV. CONCLUSION: In this study, women living with HIV on long-standing ART had increased VF prevalence compared to the slightly older group of women without HIV. Age and BMI were independent predictors for BMD at the lumbar spine, hip, and femoral neck among women living with HIV, and there was a treatment gap among women who met criteria for osteoporosis treatment. Larger studies are needed in this region to identify individuals at risk for fracture and to inform prevention guidelines.