Our goal is to present recent progress in understanding the biological mechanisms underlying anemia from a public health perspective. We describe important advances in understanding common causes of anemia and their interactions, including iron deficiency (ID), lack of other micronutrients, infection, inflammation, and genetic conditions. ID develops if the iron circulating in the blood cannot provide the amounts required for red blood cell production and tissue needs. ID anemia develops as iron-limited red blood cell production fails to maintain the hemoglobin concentration above the threshold used to define anemia. Globally, absolute ID (absent or reduced body iron stores that do not meet the need for iron of an individual but may respond to iron supplementation) contributes to only a limited proportion of anemia. Functional ID (adequate or increased iron stores that cannot meet the need for iron because of the effects of infection or inflammation and does not respond to iron supplementation) is frequently responsible for anemia in low- and middle-income countries. Absolute and functional ID may coexist. We highlight continued improvement in understanding the roles of infections and inflammation in causing a large proportion of anemia. Deficiencies of nutrients other than iron are less common but important in some settings. The importance of genetic conditions as causes of anemia depends upon the specific inherited red blood cell abnormalities and their prevalence in the settings examined. From a public health perspective, each setting has a distinctive composition of components underlying the common causes of anemia. We emphasize the coincidence between regions with a high prevalence of anemia attributed to ID (both absolute and functional), those with endemic infections, and those with widespread genetic conditions affecting red blood cells, especially in sub-Saharan Africa and regions in Asia and Oceania.

Many countries lack reliable data on anaemia prevalence, especially for populations beyond young children and women of reproductive age. Few national surveys measure both anaemia and its underlying causes. We call for the creation of a standardised global data repository and the development of a harmonised micronutrient survey platform to collect comprehensive, periodic data. We also recommend better integration of data across sources, including household surveys and other health data sources, and inclusion of haemoglobin assessment in existing survey platforms that already collect venous blood. Continued financial support and coordination of demographic and health surveys are crucial, especially in light of potential reductions in U.S. funding for global data initiatives. The causes of anaemia are multifactorial including iron deficiency, other micronutrient deficiencies, infections, inflammation, blood loss, and inherited blood disorders. We identify critical knowledge gaps in the complex interactions between these risk factors across life stages in different populations. We recommend targeted research to elucidate underlying mechanisms, improved tools for assessing anaemia determinants, advanced nutritional interventions, and integration of infection control with nutrition programs. Specific areas highlighted for further research include optimising iron dosing and formulations, effective combinations of micronutrients, improving fortification and biofortification strategies, and evaluating non-nutritional interventions such as delayed cord clamping and infection control, and management of heavy menstrual bleeding and post-partum haemorrhage. We also emphasise the need to address environmental factors contributing to anaemia, such as air pollution and climate change. Effective implementation of anaemia control programs requires tailored, multi-sectorial strategies and ongoing monitoring. Our key recommendations for effective implementation of anaemia reduction programmes are: (1) developing clear governance structures at global, national and sub-national levels to ensure proper oversight and accountability; (2) broadening national nutrition plans to incorporate cross-sector coordination and efficient management of anaemia-related strategies, and (3) placing social equity and fundamental human rights at the centre of anaemia-focused policies and interventions. This Commission critically evaluates the process by which the 2030 anaemia targets were set and proposes a more evidence-based, context-specific approach. Key limitations of the current 50% anaemia reduction target are: (1) not clearly accounting for country-specific contexts; (2) focussing on overall prevalence of anaemia rather than anaemia disease burden; and (3) a reduction target for magnitude that was unachievable using available interventions even if maximally deployed. We proposed a novel target-setting framework based on health economic modelling. This approach incorporates national anaemia prevalence, current intervention coverage and effectiveness, potential scale-up costs, and a range of potential country-specific cost-effectiveness thresholds. This approach aims to balance ambition with achievability while maintaining a unified global vision. Preliminary application of this method suggests a global summary target of 12–22% reduction in anaemia prevalence, significantly lower than the current 50% target, with marked variation in country-specific targets. We advocate for a participatory, iterative target-setting process aligning with local priorities and resources. Reducing the burden of anaemia requires a comprehensive, multi-sectorial approach that considers its complex aetiology and varied impacts across populations. By adopting the recommendations outlined in this Commission—including improved data systems, more targeted research, integrated programme implementation, and evidence-based target-setting—the global health community can renew momentum toward meaningful anaemia reduction. Achieving progress will require sustained political commitment, increased investment, and coordinated action from governments, international agencies, civil society, and researchers. As the global health agenda evolves beyond the 2030 Sustainable Development Goals, the insights and strategies presented in this Commission offer a roadmap for a more effective, equitable, and sustainable approach to tackling anaemia worldwide.

Severe anaemia and invasive bacterial infections remain important causes of hospitalization and death among young African children. The emergence and spread of antimicrobial resistance demand better understanding of bacteraemia risk factors to inform prevention strategies. Epidemiological studies have reported an association between severe anaemia and bacteraemia. In this review, we explore evidence that severe anaemia is associated with increased risk of invasive bacterial infections in young children. We describe mechanisms of iron dysregulation in severe anaemia that might contribute to increased risk and pathogenesis of invasive bacteria, recent advances in knowledge of how iron deficiency and severe anaemia impair immune responses to bacterial infections and vaccines, and the gaps in our understanding of mechanisms underlying severe anaemia, iron deficiency, and the risk of invasive bacterial infections.

Severe anaemia and invasive bacterial infections are common causes of childhood sickness and death in sub-Saharan Africa. Accumulating evidence suggests that severely anaemic African children may have a higher risk of invasive bacterial infections. However, the mechanisms underlying this association remain poorly described. Severe anaemia is characterized by increased haemolysis, erythropoietic drive, gut permeability, and disruption of immune regulatory systems. These pathways are associated with dysregulation of iron homeostasis, including the downregulation of the hepatic hormone hepcidin. Increased haemolysis and low hepcidin levels potentially increase plasma, tissue and intracellular iron levels. Pathogenic bacteria require iron and/or haem to proliferate and have evolved numerous strategies to acquire labile and protein-bound iron/haem. In this review, we discuss how severe anaemia may mediate the risk of invasive bacterial infections through dysregulation of hepcidin and/or iron homeostasis, and potential studies that could be conducted to test this hypothesis.

Radiation‐attenuated sporozoites induce sterilizing immunity and remain the 'gold standard' for malaria vaccine development. Despite practical challenges in translating these whole sporozoite vaccines to large‐scale intervention programmes, they have provided an excellent platform to dissect the immune responses to malaria pre‐erythrocytic (PE) stages, comprising both sporozoites and exoerythrocytic forms. Investigations in rodent models have provided insights that led to the clinical translation of various vaccine candidates—including RTS,S/AS01, the most advanced candidate currently in a trial implementation programme in three African countries. With advances in immunology, transcriptomics and proteomics, and application of lessons from past failures, an effective, long‐lasting and wide‐scale malaria PE vaccine remains feasible. This review underscores the progress in PE vaccine development, focusing on our understanding of host‐parasite immunological crosstalk in the tissue environments of the skin and the liver. We highlight possible gaps in the current knowledge of PE immunity that can impact future malaria vaccine development efforts.

Background: Despite the high infectivity of SARS-CoV-2, the incidence of COVID-19 in Africa has been slower than predicted. We aimed to investigate a possible association between parasitic infections and COVID-19. Methods: An ecological study in which we analysed WHO data on COVID-19 cases in comparison to WHO data on helminths and malaria cases using correlation, regression, and Geographical Information Services analyses. Results: Of the global 3.34 million COVID-19 cases and 238,628 deaths as at May 4th 2020, Africa reported 0.029/3.3 million (0.88%) cases and 1,064/238,628 (0.45%) deaths. In 2018, Africa reported 213/229 million (93%) of all malaria cases, 204/229 million (89%) of schistosomiasis cases, and 271/1068 million (25%) of soil-transmitted helminth cases globally. In contrast, Europe reported 1.5/3.3 million (45%) of global COVID-19 cases and 142,667/238,628 (59%) deaths. Europe had 5.8/1068 million (0.55%) soil-transmitted helminths cases and no malaria/schistosomiasis cases in 2018. We found an inverse correlation between the incidence of COVID-19 and malaria (r -0.17, p =0.002) and COVID-19 and soil-transmitted helminths (r -0.25, p <0.001). Malaria-endemic countries were less likely to have COVID-19 (OR 0.51, 95% CI 0.29-0.90; p =0.02). Similarly, countries endemic for soil-transmitted helminths were less likely to have COVID-19 (OR 0.24, 95% CI 0.13-0.44; p <0.001), as were countries endemic for schistosomiasis (OR 0.22, 95% CI 0.11-0.45; p<0.001). Conclusions: One plausible hypothesis for the comparatively low COVID-19 cases/deaths in parasite-endemic areas is immunomodulation induced by parasites. Studies to elucidate the relationship between parasitic infections and susceptibility to COVID-19 at an individual level are warranted.