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  1. Kwasek K, Thorne-Lyman AL, Phillips M
    Crit Rev Food Sci Nutr, 2020;60(22):3822-3835.
    PMID: 31983214 DOI: 10.1080/10408398.2019.1708698
    Achieving Sustainable Development Goal 2 of zero hunger and malnutrition by 2030 will require dietary shifts that include increasing the consumption of nutrient dense foods by populations in low- and middle-income countries. Animal source foods are known to be rich in a number of highly bioavailable nutrients that otherwise are not often consumed in the staple-food based diets of poorer populations throughout the world. Fish is the dominant animal source food in many low- and middle-income countries in the global south and is available from both fisheries and aquaculture. Consumers often perceive that wild caught fish have higher nutritional value than fish produced through aquaculture, and this may be true for some nutrients, for example omega-3 fatty acid content. However, there is potential to modify the nutritional value of farmed fish through feeds and through production systems, illustrated by the common practice of supplementing omega-3 fatty acids in fish diets to optimize their fatty acid profile. This manuscript reviews the evidence related to fish feeds and the nutritional composition of fish with respect to a number of nutrients of interest to human health, including iron, zinc, vitamins A and D, selenium, calcium, and omega-3 fatty acids, with low- and middle-income country populations in mind. In general, we find that the research on fortification of fish diet particularly with vitamins and minerals has not been directed toward human health but rather toward improvement of fish growth and health performance. We were unable to identify any studies directly exploring the impact of fish feed modification on the health of human consumers of fish, but as nutrition and health rises in the development agenda and consumer attention, the topic requires more urgent attention in future feed formulations.
  2. Chandyo RK, Henjum S, Ulak M, Thorne-Lyman AL, Ulvik RJ, Shrestha PS, et al.
    Eur J Clin Nutr, 2016 Apr;70(4):456-62.
    PMID: 26626049 DOI: 10.1038/ejcn.2015.199
    INTRODUCTION: Iron deficiency anemia is a widespread public health problem, particularly in low- and middle-income countries. Maternal iron status around and during pregnancy may influence infant iron status. We examined multiple biomarkers to determine the prevalence of iron deficiency and anemia among breastfed infants and explored its relationship with maternal and infant characteristics in Bhaktapur, Nepal.
    SUBJECTS/METHODS: In a cross-sectional survey, we randomly selected 500 mother-infant pairs from Bhaktapur municipality. Blood was analyzed for hemoglobin, ferritin, total iron-binding capacity, transferrin receptors and C-reactive protein.
    RESULTS: The altitude-adjusted prevalence of anemia was 49% among infants 2-6-month-old (hemaglobin (Hb) <10.8 g/dl) and 72% among infants 7-12-month-old (Hb <11.3 g/dl). Iron deficiency anemia, defined as anemia and serum ferritin <20 or <12 μg/l, affected 9 and 26% of infants of these same age groups. Twenty percent of mothers had anemia (Hb <12.3 g/dl), but only one-fifth was explained by depletion of iron stores. Significant predictors of infant iron status and anemia were infant age, sex and duration of exclusive breastfeeding and maternal ferritin concentrations.
    CONCLUSIONS: Our findings suggest that iron supplementation in pregnancy is likely to have resulted in a low prevalence of postpartum anemia. The higher prevalence of anemia and iron deficiency among breastfed infants compared with their mothers suggests calls for intervention targeting newborns and infants.
  3. Thorne-Lyman AL, Valpiani N, Akter R, Baten MA, Genschick S, Karim M, et al.
    Food Nutr Bull, 2017 Sep;38(3):354-368.
    PMID: 28618837 DOI: 10.1177/0379572117709417
    BACKGROUND: Fish is a widely available animal-source food in Bangladesh and a rich source of nutrients, yet little is known about practices related to incorporating fish into the diets of infants and young children.

    OBJECTIVE: Use dietary diversity data to explore consumption patterns of fish and high-quality food items within the household and examine factors associated with delayed introduction of fish to infants and young children.

    METHODS: Cross-sectional survey of 496 households with children <36 months participating in the Aquaculture for Income and Nutrition project in Bangladesh. Data collected included household characteristics, women's dietary diversity score, and minimum dietary diversity score along with data on Infant and Young Child Feeding practices.

    RESULTS: Most children (63.4%) met the threshold for minimum dietary diversity. Despite having received extensive nutrition education related to including fish in complementary foods, only half of the caretakers introduced fish at 6 months and the mean age of introduction of small fish was 8.7 months. Meat and fish were not common in infant diets but increased with child age. Concerns about bones were a major barrier to incorporating fish into infant diets.

    CONCLUSION: Given its nutrient profile and widespread availability in certain contexts, fish could be an underutilized opportunity to improve nutrition and health outcomes of infants and young children. Further research, including utilizing food processing technologies, is needed to develop appropriate responses to overcome these barriers.

  4. Haugen J, Ulak M, Chandyo RK, Henjum S, Thorne-Lyman AL, Ueland PM, et al.
    Nutrients, 2016 Dec 21;8(12).
    PMID: 28009810 DOI: 10.3390/nu8120825
    BACKGROUND: Describing vitamin D status and its predictors in various populations is important in order to target public health measures.

    OBJECTIVES: To describe the status and predictors of vitamin D status in healthy Nepalese mothers and infants.

    METHODS: 500 randomly selected Nepalese mother and infant pairs were included in a cross-sectional study. Plasma 25(OH)D concentrations were measured by LC-MS/MS and multiple linear regression analyses were used to identify predictors of vitamin D status.

    RESULTS: Among the infants, the prevalence of vitamin D insufficiency (25(OH)D <50 nmol/L) and deficiency (<30 nmol/L) were 3.6% and 0.6%, respectively, in contrast to 59.8% and 14.0% among their mothers. Infant 25(OH)D concentrations were negatively associated with infant age and positively associated with maternal vitamin D status and body mass index (BMI), explaining 22% of the variability in 25(OH)D concentration. Global solar radiation, maternal age and BMI predicted maternal 25(OH)D concentration, explaining 9.7% of its variability.

    CONCLUSION: Age and maternal vitamin D status are the main predictors of vitamin D status in infants in Bhaktapur, Nepal, who have adequate vitamin D status despite poor vitamin D status in their mothers.

  5. Strand TA, Ulak M, Kvestad I, Henjum S, Ulvik A, Shrestha M, et al.
    Pediatr Res, 2018 11;84(5):611-618.
    PMID: 29967525 DOI: 10.1038/s41390-018-0072-2
    BACKGROUND: Many children worldwide have poor vitamin B12 status. The objective of this study was to estimate association between maternal and infant vitamin B12 status and long-term growth.

    METHODS: We randomly selected 500 Nepali mother-infant pairs and measured maternal intake and infant and maternal vitamin B12 status using plasma cobalamin, total plasma homocysteine, and methylmalonic acid concentrations. We revisited available children when they were 5 years old and measured growth. The associations between intake and maternal and infant markers of vitamin B12 and growth were estimated in multiple linear regression models adjusting for relevant confounders (n = 331).

    RESULTS: Maternal vitamin B12 intake and status and vitamin B12 status in infancy predicted linear growth at 5 years of age, but not during infancy. Each microgram increase in the vitamin B12 intake of the mother during infancy was associated with an increase in height of 0.4 (0.2, 0.6) height-for-age z-scores and 1.7 (0.7, 2.7) cm around the child's fifth birthday.

    CONCLUSION: Vitamin B12 status and intake in early life is an important determinant for linear growth at school age. Our findings should be verified in randomized, placebo controlled trials before translated into public health recommendations.

  6. Ulak M, Chandyo RK, Thorne-Lyman AL, Henjum S, Ueland PM, Midttun Ø, et al.
    Nutrients, 2016 Mar 08;8(3):149.
    PMID: 27005657 DOI: 10.3390/nu8030149
    Vitamin deficiencies are known to be common among infants residing in low- and middle-income countries but relatively few studies have assessed several biochemical parameters simultaneously. The objective of the study was to describe the status of vitamins (A, D, E, B₆, B12 and folate) in breastfed infants. We measured the plasma concentrations of trans retinol, 25 hydroxy vitamin D, α-tocopherol, pyridoxal 5'-phosphate, cobalamin, folate, methylmalonic acid, homocysteine, hemoglobin and C-reactive protein from 467 randomly selected infants. One in five (22%) was deficient in at least one vitamin. Mean (SD) plasma folate concentration was 73 (35) nmol/L, and no infant in the sample was folate deficient. Vitamin B₆ deficiency and vitamin B12 deficiency was found in 22% and 17% of the infants, respectively. Elevated plasma methylmalonic acid or total homocysteine concentration was found in 82% and 62% of infants, respectively. Fifteen percent of infants were vitamin A deficient and 65% were marginally deficient in vitamin A. Fewer than 5% of infants had low plasma vitamin D concentration or vitamin E concentration (α-tocopherol <9.3 µmol/L). Our results illustrate the importance of continued supplementation campaigns and support the expansion of food fortification and dietary diversification programs that target children and women in Nepal.
  7. Hicks CC, Cohen PJ, Graham NAJ, Nash KL, Allison EH, D'Lima C, et al.
    Nature, 2019 10;574(7776):95-98.
    PMID: 31554969 DOI: 10.1038/s41586-019-1592-6
    Micronutrient deficiencies account for an estimated one million premature deaths annually, and for some nations can reduce gross domestic product1,2 by up to 11%, highlighting the need for food policies that focus on improving nutrition rather than simply increasing the volume of food produced3. People gain nutrients from a varied diet, although fish-which are a rich source of bioavailable micronutrients that are essential to human health4-are often overlooked. A lack of understanding of the nutrient composition of most fish5 and how nutrient yields vary among fisheries has hindered the policy shifts that are needed to effectively harness the potential of fisheries for food and nutrition security6. Here, using the concentration of 7 nutrients in more than 350 species of marine fish, we estimate how environmental and ecological traits predict nutrient content of marine finfish species. We use this predictive model to quantify the global spatial patterns of the concentrations of nutrients in marine fisheries and compare nutrient yields to the prevalence of micronutrient deficiencies in human populations. We find that species from tropical thermal regimes contain higher concentrations of calcium, iron and zinc; smaller species contain higher concentrations of calcium, iron and omega-3 fatty acids; and species from cold thermal regimes or those with a pelagic feeding pathway contain higher concentrations of omega-3 fatty acids. There is no relationship between nutrient concentrations and total fishery yield, highlighting that the nutrient quality of a fishery is determined by the species composition. For a number of countries in which nutrient intakes are inadequate, nutrients available in marine finfish catches exceed the dietary requirements for populations that live within 100 km of the coast, and a fraction of current landings could be particularly impactful for children under 5 years of age. Our analyses suggest that fish-based food strategies have the potential to substantially contribute to global food and nutrition security.
  8. Kvestad I, Hysing M, Shrestha M, Ulak M, Thorne-Lyman AL, Henjum S, et al.
    Am J Clin Nutr, 2017 05;105(5):1122-1131.
    PMID: 28330909 DOI: 10.3945/ajcn.116.144931
    Background: Poor vitamin B-12 (cobalamin) status is widespread in South Asia. Insufficient vitamin B-12 status has been linked to poor neurodevelopment in young children.Objective: We measured the associations between vitamin B-12 status in infancy (2-12 mo) and the development and cognitive functioning in Nepalese children 5 y later.Design: Vitamin B-12 status was assessed in infancy with the use of plasma cobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA). At 5 y of age, we measured development with the use of the Ages and Stages Questionnaire, 3rd edition (ASQ-3), and cognitive functioning by using the Developmental Neuropsychological Assessment, 2nd edition (NEPSY II), in 320 children. In regression models, we estimated the associations between vitamin B-12 status, including a combined indicator of vitamin B-12 status (3cB12) and scores on the ASQ-3 and NEPSY II subtests.Results: All markers of vitamin B-12 status with the exception of plasma cobalamin were significantly associated with the total ASQ-3 scores in the multiple regression models. A 1-unit increase in the 3cB12 score was associated with an increase in the total ASQ-3 score of 4.88 (95% CI: 2.09, 7.68; P = 0.001). Increases in both plasma tHcy and MMA (indicating poorer status) were associated with a decrease in scores on the NEPSY II affect recognition and geometric puzzle subtests. Each unit increment in 3cB12 scores was associated with increases of 0.82 (95% CI: 0.49, 1.14; P < 0.0005), 0.59 (95% CI: 0.10, 1.09; P = 0.020), and 0.24 (95% CI: 0.02, 0.47; P = 0.035) in the affect recognition, geometric puzzle, and block construction scores, respectively.Conclusions: Vitamin B-12 status in infancy is associated with development and performance on social perception tasks and visuospatial abilities at 5 y of age. The long-term effects of poor vitamin B-12 status in infancy need further investigation in randomized controlled trials.
  9. Nash KL, MacNeil MA, Blanchard JL, Cohen PJ, Farmery AK, Graham NAJ, et al.
    Proc Natl Acad Sci U S A, 2022 May 31;119(22):e2120817119.
    PMID: 35605118 DOI: 10.1073/pnas.2120817119
    Fish are an important source of bioavailable micronutrients and essential fatty acids, and capture fisheries have potential to substantially reduce dietary deficiencies. Vigorous debate has focused on trade and fishing in foreign waters as drivers of inequitable distribution of volume and value of fish, but their impact on nutrient supplies from fish is unknown. We analyze global catch, trade, and nutrient composition data for marine fisheries to quantify distribution patterns among countries with differing prevalence of inadequate nutrient intake. We find foreign fishing relocates 1.5 times more nutrients than international trade in fish. Analysis of nutrient flows among countries of different levels of nutrient intake shows fishing in foreign waters predominantly (but not exclusively) benefits nutrient-secure nations, an outcome amplified by trade. Next, we developed a nutritional vulnerability framework that shows those small island developing states and/or African nations currently benefiting from trade and foreign fishing, and countries with low adaptive capacity, are most vulnerable to future changes in nutrient supplies. Climate change exacerbates vulnerabilities for many nations. Harnessing the potential of global fisheries to address dietary deficiencies will require greater attention to nutrition objectives in fisheries’ licensing deals and trade negotiations.
  10. Love DC, Allison EH, Asche F, Belton B, Cottrell RS, Froehlich HE, et al.
    Glob Food Sec, 2021 Mar;28:100494.
    PMID: 34513582 DOI: 10.1016/j.gfs.2021.100494
    The COVID-19 pandemic and subsequent lockdowns are creating health and economic crises that threaten food and nutrition security. The seafood sector provides important sources of nutrition and employment, especially in low-income countries, and is highly globalized allowing shocks to propagate. We studied COVID-19-related disruptions, impacts, and responses to the seafood sector from January through May 2020, using a food system resilience 'action cycle' framework as a guide. We find that some supply chains, market segments, companies, small-scale actors and civil society have shown initial signs of greater resilience than others. COVID-19 has also highlighted the vulnerability of certain groups working in- or dependent on the seafood sector. We discuss early coping and adaptive responses combined with lessons from past shocks that could be considered when building resilience in the sector. We end with strategic research needs to support learning from COVID-19 impacts and responses.
  11. Global Burden of Disease Pediatrics Collaboration, Kyu HH, Pinho C, Wagner JA, Brown JC, Bertozzi-Villa A, et al.
    JAMA Pediatr, 2016 Mar;170(3):267-87.
    PMID: 26810619 DOI: 10.1001/jamapediatrics.2015.4276
    IMPORTANCE: The literature focuses on mortality among children younger than 5 years. Comparable information on nonfatal health outcomes among these children and the fatal and nonfatal burden of diseases and injuries among older children and adolescents is scarce.

    OBJECTIVE: To determine levels and trends in the fatal and nonfatal burden of diseases and injuries among younger children (aged <5 years), older children (aged 5-9 years), and adolescents (aged 10-19 years) between 1990 and 2013 in 188 countries from the Global Burden of Disease (GBD) 2013 study.

    EVIDENCE REVIEW: Data from vital registration, verbal autopsy studies, maternal and child death surveillance, and other sources covering 14,244 site-years (ie, years of cause of death data by geography) from 1980 through 2013 were used to estimate cause-specific mortality. Data from 35,620 epidemiological sources were used to estimate the prevalence of the diseases and sequelae in the GBD 2013 study. Cause-specific mortality for most causes was estimated using the Cause of Death Ensemble Model strategy. For some infectious diseases (eg, HIV infection/AIDS, measles, hepatitis B) where the disease process is complex or the cause of death data were insufficient or unavailable, we used natural history models. For most nonfatal health outcomes, DisMod-MR 2.0, a Bayesian metaregression tool, was used to meta-analyze the epidemiological data to generate prevalence estimates.

    FINDINGS: Of the 7.7 (95% uncertainty interval [UI], 7.4-8.1) million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905.059 deaths; 95% UI, 810,304-998,125), diarrheal diseases among older children (38,325 deaths; 95% UI, 30,365-47,678), and road injuries among adolescents (115,186 deaths; 95% UI, 105,185-124,870). Iron deficiency anemia was the leading cause of years lived with disability among children and adolescents, affecting 619 (95% UI, 618-621) million in 2013. Large between-country variations exist in mortality from leading causes among children and adolescents. Countries with rapid declines in all-cause mortality between 1990 and 2013 also experienced large declines in most leading causes of death, whereas countries with the slowest declines had stagnant or increasing trends in the leading causes of death. In 2013, Nigeria had a 12% global share of deaths from lower respiratory tract infections and a 38% global share of deaths from malaria. India had 33% of the world's deaths from neonatal encephalopathy. Half of the world's diarrheal deaths among children and adolescents occurred in just 5 countries: India, Democratic Republic of the Congo, Pakistan, Nigeria, and Ethiopia.

    CONCLUSIONS AND RELEVANCE: Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies. Monitoring these trends over time is also key to understanding where interventions are having an impact. Proven interventions exist to prevent or treat the leading causes of unnecessary death and disability among children and adolescents. The findings presented here show that these are underused and give guidance to policy makers in countries where more attention is needed.

  12. Wang H, Liddell CA, Coates MM, Mooney MD, Levitz CE, Schumacher AE, et al.
    Lancet, 2014 Sep 13;384(9947):957-79.
    PMID: 24797572 DOI: 10.1016/S0140-6736(14)60497-9
    BACKGROUND: Remarkable financial and political efforts have been focused on the reduction of child mortality during the past few decades. Timely measurements of levels and trends in under-5 mortality are important to assess progress towards the Millennium Development Goal 4 (MDG 4) target of reduction of child mortality by two thirds from 1990 to 2015, and to identify models of success.

    METHODS: We generated updated estimates of child mortality in early neonatal (age 0-6 days), late neonatal (7-28 days), postneonatal (29-364 days), childhood (1-4 years), and under-5 (0-4 years) age groups for 188 countries from 1970 to 2013, with more than 29,000 survey, census, vital registration, and sample registration datapoints. We used Gaussian process regression with adjustments for bias and non-sampling error to synthesise the data for under-5 mortality for each country, and a separate model to estimate mortality for more detailed age groups. We used explanatory mixed effects regression models to assess the association between under-5 mortality and income per person, maternal education, HIV child death rates, secular shifts, and other factors. To quantify the contribution of these different factors and birth numbers to the change in numbers of deaths in under-5 age groups from 1990 to 2013, we used Shapley decomposition. We used estimated rates of change between 2000 and 2013 to construct under-5 mortality rate scenarios out to 2030.

    FINDINGS: We estimated that 6·3 million (95% UI 6·0-6·6) children under-5 died in 2013, a 64% reduction from 17·6 million (17·1-18·1) in 1970. In 2013, child mortality rates ranged from 152·5 per 1000 livebirths (130·6-177·4) in Guinea-Bissau to 2·3 (1·8-2·9) per 1000 in Singapore. The annualised rates of change from 1990 to 2013 ranged from -6·8% to 0·1%. 99 of 188 countries, including 43 of 48 countries in sub-Saharan Africa, had faster decreases in child mortality during 2000-13 than during 1990-2000. In 2013, neonatal deaths accounted for 41·6% of under-5 deaths compared with 37·4% in 1990. Compared with 1990, in 2013, rising numbers of births, especially in sub-Saharan Africa, led to 1·4 million more child deaths, and rising income per person and maternal education led to 0·9 million and 2·2 million fewer deaths, respectively. Changes in secular trends led to 4·2 million fewer deaths. Unexplained factors accounted for only -1% of the change in child deaths. In 30 developing countries, decreases since 2000 have been faster than predicted attributable to income, education, and secular shift alone.

    INTERPRETATION: Only 27 developing countries are expected to achieve MDG 4. Decreases since 2000 in under-5 mortality rates are accelerating in many developing countries, especially in sub-Saharan Africa. The Millennium Declaration and increased development assistance for health might have been a factor in faster decreases in some developing countries. Without further accelerated progress, many countries in west and central Africa will still have high levels of under-5 mortality in 2030.

    FUNDING: Bill & Melinda Gates Foundation, US Agency for International Development.

  13. Kassebaum NJ, Bertozzi-Villa A, Coggeshall MS, Shackelford KA, Steiner C, Heuton KR, et al.
    Lancet, 2014 Sep 13;384(9947):980-1004.
    PMID: 24797575 DOI: 10.1016/S0140-6736(14)60696-6
    BACKGROUND: The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery.

    METHODS: We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values.

    FINDINGS: 292,982 (95% UI 261,017-327,792) maternal deaths occurred in 2013, compared with 376,034 (343,483-407,574) in 1990. The global annual rate of change in the MMR was -0·3% (-1·1 to 0·6) from 1990 to 2003, and -2·7% (-3·9 to -1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0·4% (0·2-0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1-1262·8) in South Sudan to 2·4 (1·6-3·6) in Iceland.

    INTERPRETATION: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa.

    FUNDING: Bill & Melinda Gates Foundation.

  14. Murray CJ, Ortblad KF, Guinovart C, Lim SS, Wolock TM, Roberts DA, et al.
    Lancet, 2014 Sep 13;384(9947):1005-70.
    PMID: 25059949 DOI: 10.1016/S0140-6736(14)60844-8
    BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.

    METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets.

    FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990.

    INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action.

    FUNDING: Bill & Melinda Gates Foundation.

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