Economic impact of HIV and antiretroviral therapy on education supply in high prevalence regions.

BACKGROUND: We set out to estimate, for the three geographical regions with the highest HIV prevalence, (sub-Saharan Africa [SSA], the Caribbean and the Greater Mekong sub-region of East Asia), the human resource and economic impact of HIV on the supply of education from 2008 to 2015, the target date for the achievement of Education For All (EFA), contrasting the continuation of access to care, support and Antiretroviral therapy (ART) to the scenario of universal access. METHODOLOGY/PRINCIPAL FINDINGS: A costed mathematical model of the impact of HIV and ART on teacher recruitment, mortality and absenteeism (Ed-SIDA) was run using best available data for 58 countries, and results aggregated by region. It was estimated that (1) The impact of HIV on teacher supply is sufficient to derail efforts to achieve EFA in several countries and universal access can mitigate this. (2) In SSA, the 2008 costs to education of HIV were about half of those estimated in 2002. Providing universal access for teachers in SSA is cost-effective on education returns alone and provides a return of $3.99 on the dollar. (3) The impacts on education in the hyperendemic countries in Southern Africa will continue to increase to 2015 from its 2008 level, already the highest in the world. (4) If treatment roll-out is successful, numbers of HIV positive teachers are set to increase in all the regions studied. CONCLUSIONS/SIGNIFICANCE: The return on investing in care and support is also greater in those areas with highest impact. SSA requires increased investment in teacher support, testing and particularly ART if it is to achieve EFA. The situation for teachers in the Caribbean and East Asia is similar but on a smaller scale proportionate to the lower levels of infection and greater existing access to care and support

Establishing Global School Feeding Program Targets: How Many Poor Children Globally Should Be Prioritized, and What Would Be the Cost of Implementation?

The creation of Human Capital is dependent upon good health and education throughout the first 8,000 days of life, but there is currently under-investment in health and nutrition after the first 1,000 days. Working with governments and partners, the UN World Food Program is leading a global scale up of investment in school health, and has undertaken a strategic analysis to explore the scale and cost of meeting the needs of the most disadvantaged school age children and adolescents in low and middle-income countries globally. Of the 663 million school children enrolled in school, 328 million live where the current coverage of school meals is inadequate (20% anemia and stunting), and of these an estimated 73 million children in 60 countries are also living in extreme poverty (<USD 1.97 per day). 62.7 million of these children are in Africa, and more than 66% live in low income countries, with a substantial minority in pockets of poverty in middle-income countries. The estimated overall financial requirement for school feeding is USD 4.7 billion, increasing to USD 5.8 billion annually if other essential school health interventions are included in the package. The DCP3 (Vol 8) school feeding edition and the global coverage numbers were launched in Tunis, 2018 by the WFP Executive Director, David Beasley. These estimates continue to inform the development of WFP's global strategy for school feeding

Long-Term Impact of Malaria Chemoprophylaxis on Cognitive Abilities and Educational Attainment: Follow-Up of a Controlled Trial

OBJECTIVES: We investigated the long-term impact of early childhood malaria prophylaxis on cognitive and educational outcomes. DESIGN: This was a household-based cluster-controlled intervention trial. SETTING: The study was conducted in 15 villages situated between 32 km to the east and 22 km to the west of the town of Farafenni, the Gambia, on the north bank of the River Gambia. PARTICIPANTS: A total of 1,190 children aged 3–59 mo took part in the trial. We traced 579 trial participants (291 in the prophylaxis group and 288 in the placebo group) in 2001, when their median age was 17 y 1 mo (range 14 y 9 mo to 19 y 6 mo). INTERVENTIONS: Participants received malaria chemoprophylaxis (dapsone/pyrimethamine) or placebo for between one and three malaria transmission seasons from 1985 to 1987 during the controlled trial. At the end of the trial, prophylaxis was provided for all children under 5 y of age living in the study villages. OUTCOME MEASURES: The outcome measures were cognitive abilities, school enrolment, and educational attainment (highest grade reached at school). RESULTS: There was no significant overall intervention effect on cognitive abilities, but there was a significant interaction between intervention group and the duration of post-trial prophylaxis (p = 0.034), with cognitive ability somewhat higher in the intervention group among children who received no post-trial prophylaxis (treatment effect = 0.2 standard deviations [SD], 95% confidence interval [CI] −0.03 to 0.5) and among children who received less than 1 y of post-trial prophylaxis (treatment effect = 0.4 SD, 95% CI 0.1 to 0.8). The intervention group had higher educational attainment by 0.52 grades (95% CI = −0.041 to 1.089; p = 0.069). School enrolment was similar in the two groups. CONCLUSIONS: The results are suggestive of a long-term effect of malaria prophylaxis on cognitive function and educational attainment, but confirmatory studies are needed

Assays to Detect β-Tubulin Codon 200 Polymorphism in Trichuris trichiura and Ascaris lumbricoides

The soil-transmitted helminths Ascaris lumbricoides and Trichuris trichiura are gastrointestinal nematodes causing many disabilities in tropical parts of the developing world. Control programs, such as “The Focussing Resources on Effective School Health” (FRESH) Partnership, have been implemented to remove human soil-transmitted nematodes through large-scale use of benzimidazole anthelmintic drugs for school-aged children in developing countries. The benzimidazole drugs albendazole and mebendazole are commonly used as a single annual treatment in areas where the burden is high. In veterinary nematodes, repeated use of these anthelmintics has selected for resistant populations. Resistance to benzimidazoles is commonly associated with a single amino acid substitution from phenylalanine to tyrosine in the β-tubulin gene at position 200. In this study, we have developed pyrosequencing assays for codon 200 in A. lumbricoides and T. trichiura to screen for this single nucleotide polymorphism (SNP) in β-tubulin. The 200Tyr SNP was detected at low frequency in T. trichiura from non-treated people from Kenya and at high frequency in T. trichiura from treated people from Panama. The presence of the resistance-associated SNP may play a role in the sometimes low and variable efficacy of benzimidazole anthelmintics against T. trichiura

Re-Imagining School Feeding : A High-Return Investment in Human Capital and Local Economies

Analysis shows that a quality education, combined with a guaranteed package of health and nutrition interventions at school, such as school feeding, can contribute to child and adolescent development and build human capital. School feeding programs can help get children into school and help them stay there, increasing enrollment and reducing absenteeism. Once children are in the classroom, these programs can contribute to their learning by avoiding hunger and enhancing cognitive abilities. The benefits are especially great for the poorest and most disadvantaged children. As highlighted in the World Bank’s 2018 World Development Report (World Bank 2018), countries need to prioritize learning, not just schooling. Children must be healthy, not hungry, if they are to match learning opportunities with the ability to learn. In the most vulnerable communities, nutrition-sensitive school meals can offer children a regular source of nutrients that are essential for their mental and physical development. And for the growing number of countries with a “double burden” of undernutrition and emerging obesity problems, well-designed school meals can help set children on the path toward more healthy diets. In Latin America, for example, where there is a growing burden of noncommunicable diseases (NCDs), school feeding programs are a key intervention in reducing undernutrition and promoting healthy diet choices. Mexico’s experience reducing sugary beverages in school cafeterias, for example, was found to be beneficial in advancing a healthy lifestyle. A large trial of school-based interventions in China also found that nutritional or physical activity interventions alone are not as effective as a joint program that combines nutritional and educational interventions. In poor communities, economic benefits from school feeding programs are also evident—reducing poverty by boosting income for households and communities as a whole. For families, the value of meals in school is equivalent to about 10 percent of a household’s income. For families with several children, that can mean substantial savings. As a result, school feeding programs are often part of social safety nets in poor countries, and they can be a stable way to reliably target pro-poor investments into communities, as well as a system that can be scaled up rapidly to respond to crises. There are also direct economic benefits for smallholder farmers in the community. Buying local food creates stable markets, boosting local agriculture, impacting rural transformation, and strengthening local food systems. In Brazil, for example, 30 percent of all purchases for school feeding come from smallholder agriculture (Drake and others 2016). These farmers are oftentimes parents with schoolchildren, helping them break intergenerational cycles of hunger and poverty. Notably, benefits to households and communities offer important synergies. The economic growth in poor communities helps provide stability and better-quality education and health systems that promote human capital. At the same time, children and adolescents grow up to enjoy better employment and social opportunities as their communities grow

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

HIV as Part of the Lives of Children and Youth as Life Expectancy Increases : Implications for Education

The education sector is crucial to any national response to the world epidemic of HIV and AIDS. The school age years, about 5 to 15 years, make up the cross section of any population with the lowest prevalence of HIV infection. This is the “Window of Hope", and education is the social vaccine against HIV infection. Now, with effective anti-viral treatment increasingly available, the number of infected children of school age is rising through increased survival. Schools must adapt to having more such children in class. Furthermore, there will be many infected and affected children, orphans and vulnerable children, who will not access formal education, or not fully, and the path to education must be made easier for them. We are able to predict a rise and then a fall of the school age numbers, but new preparations must be made for these young people to adapt to their adult lives, living with HIV. All such school and educational responses must take the developmental stages of children and their emotional needs into account