The Next WHO Director-General’s Highest Priority: a Global Treaty on the Human Right to Health

Amidst the many challenges facing the next WHO Director-General, the new WHO head should find WHO’s foremost priority in its most important constitutional pillar: the right to health. The centerpiece of this endeavor should be leadership on the Framework Convention on Global Health (FCGH), the proposed global treaty based in the right to health and aimed at national and global health equity. The treaty would reform global governance for health to enhance accountability, transparency, and civil society participation and protect the right to health in trade, investment, climate change, and other international regimes, while catalyzing governments to institutionalize the right to health at community through to national levels. It would usher in a new era of global health with justice – vast improvements in health outcomes, equitably distributed. With the Framework Convention on Tobacco Control having served as a proof of concept, the FCGH would be an innovative treaty finding solutions to overcome global health failings in accountability, equality, financing, and inter-sectoral coherence. It would include a global health accountability framework, encompassing, civil society engagement, independent monitoring, and plans for redress, while catalyzing national health accountability strategies, accountability mechanisms, disaggregated data, and community participation. National health equity strategies, pro-poor pathways to universal health coverage, and robust non-discrimination provisions could elevate the voices, priorities, and ultimately power of marginalized populations. The FCGH would include a national and global health financing framework, while reaching beyond the health sector with right to health assessments, public health participation in developing international agreements, and responsibility for all sectors for improving health outcomes. The FCGH would reinvigorate WHO’s global health leadership, breathing new life into its founding principles. It could become the platform for reforming WHO as a rights-based 21st century institution, with badly-needed reforms, such as community participation, new priorities favouring social determinants of health, and a culture of transparency and accountability. The next Director-General should launch a historic effort to align national and global governance for with human rights through the FCGH, bringing the world closer to global health with justice

The WHO’s 75th anniversary: WHO at a pivotal moment in history

The World Health Organisation (WHO) was inaugurated in 1948 to bring the world together to ensure the highest attainable standard of health for all. Establishing health governance under the United Nations (UN), WHO was seen as the preeminent leader in public health, promoting a healthier world following the destruction of World War II and ensuring global solidarity to prevent disease and promote health. Its constitutional function would be ‘to act as the directing and coordinating authority on international health work’. Yet today, as the world commemorates WHO’s 75th anniversary, it faces a historic global health crisis, with governments presenting challenges to its institutional legitimacy and authority amid the ongoing COVID-19 pandemic. WHO governance in the coming years will define the future of the Organisation and, crucially, the health and well-being of billions of people across the globe. At this pivotal moment, WHO must learn critical lessons from its past and make fundamental reforms to become the Organisation it was meant to be. We propose reforms in WHO financing, governance, norms, human rights and equity that will lay a foundation for the next generation of global governance for health

RXRs control serous macrophage neonatal expansion and identity and contribute to ovarian cancer progression

Tissue-resident macrophages (TRMs) populate all tissues and play key roles in homeostasis, immunity and repair. TRMs express a molecular program that is mostly shaped by tissue cues. However, TRM identity and the mechanisms that maintain TRMs in tissues remain poorly understood. We recently found that serous-cavity TRMs (LPMs) are highly enriched in RXR transcripts and RXR-response elements. Here, we show that RXRs control mouse serous-macrophage identity by regulating chromatin accessibility and the transcriptional regulation of canonical macrophage genes. RXR deficiency impairs neonatal expansion of the LPM pool and reduces the survival of adult LPMs through excess lipid accumulation. We also find that peritoneal LPMs infiltrate early ovarian tumours and that RXR deletion diminishes LPM accumulation in tumours and strongly reduces ovarian tumour progression in mice. Our study reveals that RXR signalling controls the maintenance of the serous macrophage pool and that targeting peritoneal LPMs may improve ovarian cancer outcomes.This work was supported by a HFSP fellowship to M.C-A. (LT000110/2015-L/1), grants from the Spanish Ministerio de Ciencia e Innovación (MCI) (SAF2015-64287R, SAF2017-90604-REDT-NurCaMein, RTI2018-095928-B100), La Marató de TV3 Foundation (201605-32) and Comunidad de Madrid (MOIR-B2017/BMD-3684) to M.R, and the Formación de Profesorado Universitario (FPU17/01731) programme (MCI) to J.P. The CNIC is supported by the MCI and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Institutional and behaviour-change interventions to support COVID-19 public health measures: a review by the Lancet Commission Task Force on public health measures to suppress the pandemic

The Lancet COVID-19 Commission Task Force for Public Health Measures to Suppress the Pandemic was launched to identify critical points for consideration by governments on public health interventions to control coronavirus disease 2019 (COVID-19). Drawing on our review of published studies of data analytics and modelling, evidence synthesis and contextualisation, and behavioural science evidence and theory on public health interventions from a range of sources, we outline evidence for a range of institutional measures and behaviour-change measures. We cite examples of measures adopted by a range of countries, but especially jurisdictions that have, thus far, achieved low numbers of COVID-19 deaths and limited community transmission of severe acute respiratory syndrome coronavirus 2. Finally, we highlight gaps in knowledge where research should be undertaken. As countries consider long-term measures, there is an opportunity to learn, improve the response and prepare for future pandemics.publishedVersio

The phosphorylation landscape of infection-related development by the rice blast fungus

Many of the world’s most devastating crop diseases are caused by fungal pathogens that elaborate specialized infection structures to invade plant tissue. Here, we present a quantitative mass-spectrometry-based phosphoproteomic analysis of infection-related development by the rice blast fungus Magnaporthe oryzae, which threatens global food security. We mapped 8,005 phosphosites on 2,062 fungal proteins following germination on a hydrophobic surface, revealing major re-wiring of phosphorylation-based signaling cascades during appressorium development. Comparing phosphosite conservation across 41 fungal species reveals phosphorylation signatures specifically associated with biotrophic and hemibiotrophic fungal infection. We then used parallel reaction monitoring (PRM) to identify phosphoproteins regulated by the fungal Pmk1 MAPK that controls plant infection by M. oryzae. We define 32 substrates of Pmk1 and show that Pmk1-dependent phosphorylation of regulator Vts1 is required for rice blast disease. Defining the phosphorylation landscape of infection therefore identifies potential therapeutic interventions for the control of plant diseases

Prioritization of invasive alien species with the potential to threaten agriculture and biodiversity in Kenya through horizon scanning

Invasive alien species (IAS) rank among the most significant drivers of species extinction and ecosystem degradation resulting in significant impacts on socio-economic development. The recent exponential spread of IAS in most of Africa is attributed to poor border biosecurity due to porous borders that have failed to prevent initial introductions. In addition, countries lack adequate information about potential invasions and have limited capacity to reduce the risk of invasions. Horizon scanning is an approach that prioritises the risks of potential IAS through rapid assessments. A group of 28 subject matter experts used an adapted methodology to assess 1700 potential IAS on a 5-point scale for the likelihood of entry and establishment, potential socio-economic impact, and impact on biodiversity. The individual scores were combined to rank the species according to their overall potential risk for the country. Confidence in individual and overall scores was recorded on a 3-point scale. This resulted in a priority list of 120 potential IAS (70 arthropods, 9 nematodes, 15 bacteria, 19 fungi/chromist, 1 viroid, and 6 viruses). Options for risk mitigation such as full pest risk analysis and detection surveys were suggested for prioritised species while species for which no immediate action was suggested, were added to the plant health risk register and a recommendation was made to regularly monitor the change in risk. By prioritising risks, horizon scanning guides resource allocation to interventions that are most likely to reduce risk and is very useful to National Plant Protection Organisations and other relevant stakeholders

Alma-Ata 30 years on: revolutionary, relevant, and time to revitalise.

In this paper, we revisit the revolutionary principles-equity, social justice, and health for all; community participation; health promotion; appropriate use of resources; and intersectoral action-raised by the 1978 Alma-Ata Declaration, a historic event for health and primary health care. Old health challenges remain and new priorities have emerged (eg, HIV/AIDS, chronic diseases, and mental health), ensuring that the tenets of Alma-Ata remain relevant. We examine 30 years of changes in global policy to identify the lessons learned that are of relevance today, particularly for accelerated scale-up of primary health-care services necessary to achieve the Millennium Development Goals, the modern iteration of the "health for all" goals. Health has moved from under-investment, to single disease focus, and now to increased funding and multiple new initiatives. For primary health care, the debate of the past two decades focused on selective (or vertical) versus comprehensive (horizontal) delivery, but is now shifting towards combining the strengths of both approaches in health systems. Debates of community versus facility-based health care are starting to shift towards building integrated health systems. Achievement of high and equitable coverage of integrated primary health-care services requires consistent political and financial commitment, incremental implementation based on local epidemiology, use of data to direct priorities and assess progress, especially at district level, and effective linkages with communities and non-health sectors. Community participation and intersectoral engagement seem to be the weakest strands in primary health care. Burgeoning task lists for primary health-care workers require long-term human resource planning and better training and supportive supervision. Essential drugs policies have made an important contribution to primary health care, but other appropriate technology lags behind. Revitalisng Alma-Ata and learning from three decades of experience is crucial to reach the ambitious goal of health for all in all countries, both rich and poor

Community health workers at the dawn of a new era: 11. CHWs leading the way to "Health for All"

Background: This is the concluding paper of our 11-paper supplement, "Community health workers at the dawn of a new era". Methods: We relied on our collective experience, an extensive body of literature about community health workers (CHWs), and the other papers in this supplement to identify the most pressing challenges facing CHW programmes and approaches for strengthening CHW programmes. Results: CHWs are increasingly being recognized as a critical resource for achieving national and global health goals. These goals include achieving the health-related Sustainable Development Goals of Universal Health Coverage, ending preventable child and maternal deaths, and making a major contribution to the control of HIV, tuberculosis, malaria, and noncommunicable diseases. CHWs can also play a critical role in responding to current and future pandemics. For these reasons, we argue that CHWs are now at the dawn of a new era. While CHW programmes have long been an underfunded afterthought, they are now front and centre as the emerging foundation of health systems. Despite this increased attention, CHW programmes continue to face the same pressing challenges: inadequate financing, lack of supplies and commodities, low compensation of CHWs, and inadequate supervision. We outline approaches for strengthening CHW programmes, arguing that their enormous potential will only be realized when investment and health system support matches rhetoric. Rigorous monitoring, evaluation, and implementation research are also needed to enable CHW programmes to continuously improve their quality and effectiveness. Conclusion: A marked increase in sustainable funding for CHW programmes is needed, and this will require increased domestic political support for prioritizing CHW programmes as economies grow and additional health-related funding becomes available. The paradigm shift called for here will be an important step in accelerating progress in achieving current global health goals and in reaching the goal of Health for All. Keywords: Community health worker programmes; Community health workers; Community-based primary healthcare; Ending preventable child and maternal deaths; Lay health workers; Primary healthcare; Sustainable development goals; Universal Health Coverage

Novel concepts in cervical cancer screening: a comparison of VIA, HPV DNA test and p16INK4a/Ki-67 dual stain cytology in Western Kenya

Background: Screening of unvaccinated women remains essential to mitigate the high morbidity/mortality of cervical cancer. Here, we compared visual inspection with acetic acid (VIA), recommended by WHO as the most cost-effective screening approach in LMICs, with HPV-based screening, and usage of p16INK4a/Ki-67 dual stain cytology. Methods: We prospectively enrolled women participating in a VIA-based cervical cancer screening program in two peri-urban health centers of Kenya. Consenting women had a VIA examination preceded by collection of a liquid-based cytology sample from the cervix stored in PreservCyt medium (Hologic®). Analysis of all samples included a hrHPV DNA test and evaluation of a p16INK4a /Ki-67 (CINtecPLUS®) dual stained slide that was prepared using the ThinPrep® 2000 Processor and evaluated by a pathologist trained in the methodology. Results: In 701 of a total of 800 women aged 18–64 years, all three investigations were performed and data could be analyzed. The HPV, VIA and dual stain cytology positivity were 33%, 7%, and 2% respectively. The HPV positivity rate of VIA positive cases was 32%. The five most common HPV types were HPV16, 52, 68, 58 and 35. The OR among HIV infected women of an HPV infection, VIA positivity and positive dual stain cytology were 2.6 (95%CI 1.5–4.3), 1.9 (95%CI 0.89–4.4) and 3.4 (95%CI 1.07–10.9) respectively. The sensitivity of VIA to detect a p16INK4a/Ki-67 positive transforming infection was 13% (95%CI 2–38). Conclusions: Primary HPV testing appears feasible and should be considered as a primary screening test also in LMICs. The poor sensitivity of VIA renders it unsuitable as a triage test for HPV positive women. The utility of p16INK4a/Ki-67 dual stain cytology as a triage test for HPV positive women in LMICs should be further studied

Putting health equity at heart of universal coverage: the need for national programmes of action

Submitted by Fábio Marques ([email protected]) on 2019-11-18T16:33:24Z No. of bitstreams: 1 Putting health equity_Valdilea_Veloso_INI_Lapclin-AIDS_2019.pdf: 923222 bytes, checksum: 39595a4115d3e19b8e00e1d28d9d0edf (MD5)Approved for entry into archive by Janaína Nascimento ([email protected]) on 2019-12-06T14:26:36Z (GMT) No. of bitstreams: 1 Putting health equity_Valdilea_Veloso_INI_Lapclin-AIDS_2019.pdf: 923222 bytes, checksum: 39595a4115d3e19b8e00e1d28d9d0edf (MD5)Made available in DSpace on 2019-12-06T14:26:36Z (GMT). No. of bitstreams: 1 Putting health equity_Valdilea_Veloso_INI_Lapclin-AIDS_2019.pdf: 923222 bytes, checksum: 39595a4115d3e19b8e00e1d28d9d0edf (MD5) Previous issue date: 2019O’Neill Institute for National and Global Health Law, Washington, DC, USA.O’Neill Institute for National and Global Health Law, Washington, DC, USA.O’Neill Institute for National and Global Health Law, Washington, DC, USA.National Academy of Science of Buenos Aires. Buenos Aires, Argentina.University College London. Institute of Health Equity. London, UK.Office for Equity Gender, and Cultural Diversity, Pan American Health Organization, Washington, DC, USA.University of Global Health Equity. Kigali, Rwanda.Partners In Health. Boston, MA, USA.BRAC. Dhaka, Bangladesh.University of the West Indies. Kingston, Jamaica.Fundação Oswaldo Cruz. instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Tsinghua University. Beijing, China.Champions for AIDS-Free Generation. Nairobi, Kenya