Emory Global Health Institute

BackgroundPneumococcal conjugate vaccines have reduced the incidence of invasive pneumococcal disease, caused by vaccine serotypes, but non-vaccine-serotypes remain a concern. We used whole genome sequencing to study pneumococcal serotype, antibiotic resistance and invasiveness, in the context of genetic background.MethodsOur dataset of 13,454 genomes, combined with four published genomic datasets, represented Africa (40%), Asia (25%), Europe (19%), North America (12%), and South America (5%). These 20,027 pneumococcal genomes were clustered into lineages using PopPUNK, and named Global Pneumococcal Sequence Clusters (GPSCs). From our dataset, we additionally derived serotype and sequence type, and predicted antibiotic sensitivity. We then measured invasiveness using odds ratios that relating prevalence in invasive pneumococcal disease to carriage.FindingsThe combined collections (n = 20,027) were clustered into 621 GPSCs. Thirty-five GPSCs observed in our dataset were represented by >100 isolates, and subsequently classed as dominant-GPSCs. In 22/35 (63%) of dominant-GPSCs both non-vaccine serotypes and vaccine serotypes were observed in the years up until, and including, the first year of pneumococcal conjugate vaccine introduction.Penicillin and multidrug resistance were higher (p < .05) in a subset dominant-GPSCs (14/35, 9/35 respectively), and resistance to an increasing number of antibiotic classes was associated with increased recombination (R2 = 0.27 p < .0001). In 28/35 dominant-GPSCs, the country of isolation was a significant predictor (p < .05) of its antibiogram (mean misclassification error 0.28, SD ± 0.13).We detected increased invasiveness of six genetic backgrounds, when compared to other genetic backgrounds expressing the same serotype. Up to 1.6-fold changes in invasiveness odds ratio were observed.InterpretationWe define GPSCs that can be assigned to any pneumococcal genomic dataset, to aid international comparisons. Existing non-vaccine-serotypes in most GPSCs preclude the removal of these lineages by pneumococcal conjugate vaccines; leaving potential for serotype replacement. A subset of GPSCs have increased resistance, and/or serotype-independent invasiveness.

BACKGROUND: The burden of typhoid in sub-Saharan African (SSA) countries has been difficult to estimate, in part, due to suboptimal laboratory diagnostics. However, surveillance blood cultures at two sites in Nigeria have identified typhoid associated with Salmonella enterica serovar Typhi (S. Typhi) as an important cause of bacteremia in children. METHODS: A total of 128 S. Typhi isolates from these studies in Nigeria were whole-genome sequenced, and the resulting data was used to place these Nigerian isolates into a worldwide context based on their phylogeny and carriage of molecular determinants of antibiotic resistance. RESULTS: Several distinct S. Typhi genotypes were identified in Nigeria that were related to other clusters of S. Typhi isolates from north, west and central regions of Africa. The rapidly expanding S. Typhi clade 4.3.1 (H58) previously associated with multiple antimicrobial resistances in Asia and in east, central and southern Africa, was not detected in this study. However, antimicrobial resistance was common amongst the Nigerian isolates and was associated with several plasmids, including the IncHI1 plasmid commonly associated with S. Typhi. CONCLUSIONS: These data indicate that typhoid in Nigeria was established through multiple independent introductions into the country, with evidence of regional spread. MDR typhoid appears to be evolving independently of the haplotype H58 found in other typhoid endemic countries. This study highlights an urgent need for routine surveillance to monitor the epidemiology of typhoid and evolution of antimicrobial resistance within the bacterial population as a means to facilitate public health interventions to reduce the substantial morbidity and mortality of typhoid.

Climate change threatens to reverse the gains in global child health and the reductions in global child mortality made over the past 25 years. There is broad recognition that greenhouse gases emitted by human activities are causing climate change.1,2 The problem of climate change transcends geopolitical boundaries and will have extensive impacts on child health and security (Fig 1).3 With implications for all of humanity, climate change will disproportionately affect children and the poor, magnifying existing disparities in social determinates of health.4,5Changes in temperature and weather patterns are already occurring. Global surface temperatures were the highest ever recorded in 2016, and 9 of the past 10 years were the warmest on record.6 Dramatic changes to the climate are expected to occur within the life span of current pediatric patients. The 2013 Intergovernmental Panel on Climate Change assessed that global temperatures will likely rise 2°C and may increase 4.8°C by 2100 if current trends in emissions continue (Fig 2).2,7 In the same scenario, the average global sea level rise will accelerate, and seas will likely rise 45 to 82 cm by 2100, relative to 1986–2005 levels.2 Economic damage in the United States is predicted to be 1.2% of gross domestic product for every 1°C increase in temperature.8 Natural disasters will increase in frequency and intensity.2 These climate-related threats are widely considered the most significant global health challenge of our lifetime.9Globally, children are estimated to bear 88% of the burden of disease due to climate change, with the poorest disproportionately affected.10,11 All children depend on the resources of caregivers and communities to buffer against environmental threats, including climate-related health threats. Children in communities with limited resources to adapt to climate change face an even higher risk of adverse environmental exposure. When exposure results in illness, disability, or death, the loss of potential healthy life is greater for the youngest, resulting in a greater burden of disease measured by disability-adjusted-life-years for children.10 Using projections of the distribution of mortality from climate-related health threats, researchers anticipate a disproportionate impact on the world’s poorest citizens (Fig 3).11The evident geographic disparity in climate vulnerability likely overlays a similar age-based disparity: deaths in young children account for a disproportionate share of total deaths due to climate-sensitive health threats. In 2015, deaths in children <5 years old accounted for 38%, 65%, and 48% of global deaths due to diarrhea, malaria, and nutritional deficiencies, respectively.12 The projected increase in these diseases due to climate change corresponds to a considerable burden of preventable child deaths, particularly in low-income countries.The attributable risk from specific exposures (like extreme heat and ozone) stems not only from the degree of increase but also from the ubiquity of the exposure.13 Researchers estimate that 74% of the world’s population (up from 30% today) will be exposed to at least 20 days of lethal heat per year by 2100 if current emission trends continue.14 Children are particularly vulnerable to extreme heat: they have a high surface area to mass ratio and must divert more cardiac output to their skin to dissipate heat.15 Although variability exists in the literature on heat stress in children, Basagaña et al16 found that infant mortality increased 25% on extremely hot days, with the first 7 days of life representing a period of critical vulnerability. High ambient temperature coupled with emissions have well-documented negative effects on pulmonary health in children.13,17 Air pollution decreases total lung volume and has negative impacts on lung function that may be lifelong.18,19 Increases in ambient temperature and ozone levels directly correlate with pediatric emergency department visits for asthma exacerbation.20,21 The research on climate and respiratory illness exemplifies the many-faceted implications of climate change on child health. Even in this well-studied realm, there is a dearth of data on children in resource-limited settings, and those children are the least able to modify their exposure risk.These children are also most vulnerable to scarcity of basic natural resources (potable water and food) aggravated by droughts and flooding. Almost 160 million children live in high or extremely high drought zones and over 500 million inhabit areas with extremely high flood occurrence.22 Increased amplitudes of drought and flood events are projected to stress agricultural systems, exacerbate food and water insecurity, and increase childhood undernutrition.23,24 The World Health Organization projects that there will be 77 000 to 131 000 additional deaths in children under 5 from climate-related undernutrition in 2030.25 Contributing to 45% of total deaths in children <5 years old, undernutrition compromises the immune system and blunts long-term developmental potential.26,27 Scarcity of rainfall has been linked to environmental conflict.28,29 Conflict and migration, in turn, further stress the environment, agricultural system, and local populations in a vicious cycle that erodes basic social determinants of health.Natural disasters also lead to displacement of families and children. Extreme weather events are increasing in frequency and intensity, undermining the stability of home and community for growing numbers of children, with risks to their security and physical and mental health.3,30 The Internal Displacement Monitoring Center estimates that more than 26 million people per year have left their homes because of natural disasters since 2008, a likelihood of displacement twice that of 1970.31 Over half of internationally displaced refugees were children.32 Displaced children face substantial health risks, including malnutrition, infection, traumatic stress, and physical or sexual abuse.33 Disasters also disrupt the medical supply chain, compromising vaccination programs and the availability of medications. In 2017, Hurricane Maria disrupted the production of drugs and intravenous fluid manufactured in Puerto Rico, resulting in global shortages.34 The results of natural disasters are felt globally.The potential for the rapid spread of infectious diseases in a world connected by global travel and commerce further illustrates the compass of climate change. Among its ecological impacts are anticipated increases in many infectious illnesses, alterations in vector-borne diseases, and more rapid disease emergence.35 Increased temperatures are associated with an increased incidence of bacterial causes of diarrhea.36 The World Health Organization estimates an additional 48 000 deaths per year from diarrheal diseases in children <15 years old by 2030.37 The re-emergence of Chikungunya (with its expansion into the western hemisphere) has been linked to changing climates in Southeast Asia.38 Likewise, warmer climates are thought to have contributed to the Zika virus pandemic, with studies detailing the effect of warmer temperatures on the range, life cycle, and feeding patterns of Aedes aegypti mosquitos.35These are select examples of research (and knowledge gaps) on the health impacts of climate change in children. Pediatricians are positioned to reframe this urgent debate from one of political interests to one of monumental global health importance. We must advocate for child-specific research on climate change and health as well as incorporation of child-specific needs in disaster preparedness plans and climate adaptation policies.39 We must be prepared to respond to surges of child injury and illness in the aftermath of a disaster when health infrastructure itself is likely to be compromised. We can lead in adopting climate-friendly practices in our own personal and professional realms, taking stock of our energy, transportation, and food sources and choices.40 Collective acts to prepare for and (most urgently) to limit the magnitude of climate change will help protect children around the globe from preventable illness and death. In the interim, our collective inaction may be to the detriment of those we dedicate our careers to protecting.We recognize the contributions of Michael Forrestor to the research of this article.

BACKGROUND: Iron deficiency (ID) is a major public health burden in African children and accurate prevalence estimates are important for effective nutritional interventions. However, ID may be incorrectly estimated in Africa because most measures of iron status are altered by inflammation and infections such as malaria. Through the current study, we have assessed different approaches to the prediction of iron status and estimated the burden of ID in African children. METHODS: We assayed iron and inflammatory biomarkers in 4853 children aged 0-8 years from Kenya, Uganda, Burkina Faso, South Africa, and The Gambia. We described iron status and its relationship with age, sex, inflammation, and malaria parasitemia. We defined ID using the WHO guideline (ferritin < 12 μg/L or < 30 μg/L in the presence of inflammation in children < 5 years old or < 15 μg/L in children ≥ 5 years old). We compared this with a recently proposed gold standard, which uses regression-correction for ferritin levels based on the relationship between ferritin levels, inflammatory markers, and malaria. We further investigated the utility of other iron biomarkers in predicting ID using the inflammation and malaria regression-corrected estimate as a gold standard. RESULTS: The prevalence of ID was highest at 1 year of age and in male infants. Inflammation and malaria parasitemia were associated with all iron biomarkers, although transferrin saturation was least affected. Overall prevalence of WHO-defined ID was 34% compared to 52% using the inflammation and malaria regression-corrected estimate. This unidentified burden of ID increased with age and was highest in countries with high prevalence of inflammation and malaria, where up to a quarter of iron-deficient children were misclassified as iron replete. Transferrin saturation < 11% most closely predicted the prevalence of ID according to the regression-correction gold standard. CONCLUSIONS: The prevalence of ID is underestimated in African children when defined using the WHO guidelines, especially in malaria-endemic populations, and the use of transferrin saturation may provide a more accurate approach. Further research is needed to identify the most accurate measures for determining the prevalence of ID in sub-Saharan Africa.

To avoid public criticism and forestall government intervention, the food and beverage industry hopes that self-regulation is sufficient1 and also seeks to establish public-private partnerships. This reaction is common in industries under threat and can take helpful or harmful forms.

Knowledge of pneumococcal lineages, their geographic distribution and antibiotic resistance patterns, can give insights into global pneumococcal disease. We provide interactive bioinformatic outputs to explore such topics, aiming to increase dissemination of genomic insights to the wider community, without the need for specialist training. We prepared 12 country-specific phylogenetic snapshots, and international phylogenetic snapshots of 73 common Global Pneumococcal Sequence Clusters (GPSCs) previously defined using PopPUNK, and present them in Microreact. Gene presence and absence defined using Roary, and recombination profiles derived from Gubbins are presented in Phandango for each GPSC. Temporal phylogenetic signal was assessed for each GPSC using BactDating. We provide examples of how such resources can be used. In our example use of a country-specific phylogenetic snapshot we determined that serotype 14 was observed in nine unrelated genetic backgrounds in South Africa. The international phylogenetic snapshot of GPSC9, in which most serotype 14 isolates from South Africa were observed, highlights that there were three independent sub-clusters represented by South African serotype 14 isolates. We estimated from the GPSC9-dated tree that the sub-clusters were each established in South Africa during the 1980s. We show how recombination plots allowed the identification of a 20 kb recombination spanning the capsular polysaccharide locus within GPSC97. This was consistent with a switch from serotype 6A to 19A estimated to have occured in the 1990s from the GPSC97-dated tree. Plots of gene presence/absence of resistance genes ( tet , erm , cat ) across the GPSC23 phylogeny were consistent with acquisition of a composite transposon. We estimated from the GPSC23-dated tree that the acquisition occurred between 1953 and 1975. Finally, we demonstrate the assignment of GPSC31 to 17 externally generated pneumococcal serotype 1 assemblies from Utah via Pathogenwatch. Most of the Utah isolates clustered within GPSC31 in a USA-specific clade with the most recent common ancestor estimated between 1958 and 1981. The resources we have provided can be used to explore to data, test hypothesis and generate new hypotheses. The accessible assignment of GPSCs allows others to contextualize their own collections beyond the data presented here.

Anemia remains an important global health problem. Inexpensive, accurate, and noninvasive solutions are needed to monitor and evaluate anemia in resource-limited settings. We evaluated the performance of multiple point-of-care hemoglobin devices, including a novel noninvasive smartphone application tested on Apple® and Android® cell phones, Masimo Pronto®, and HemoCue® Hb-301 and Hb-801, against a gold-standard hematology analyzer (reference hemoglobin) using venous blood. We examined correlations between hemoglobin devices and reference hemoglobin, device accuracy (average bias, Bland-Altman plots, clinical performance) and classification bias (sensitivity, specificity) among 299 refugees (10mo-65y) in Atlanta, GA. Semi-structured interviews (n = 19) with participants and staff assessed usability and acceptability. Mean reference hemoglobin was 13.7 g/dL (SD:1.8) with 12.5% anemia. Noninvasive hemoglobin devices were not well correlated with reference hemoglobin (Apple® R2 = 0.08, Android® R2 = 0.11, Masimo Pronto® R2 = 0.29), but stronger correlations were reported with HemoCue® Hb-301 (R2 = 0.87) and Hb-801 (R2 = 0.88). Bias (SD) varied across each device: Apple®: -1.6 g/dL (2.0), Android®: -0.7 g/dL (2.0), Masimo Pronto®: -0.4 g/dL (1.6), HemoCue® Hb-301: +0.4 g/dL (0.7) and HemoCue® Hb-801: +0.2 g/dL (0.6). Clinically acceptable performance (within ± 1 g/dL of reference hemoglobin) was higher for the invasive devices (HemoCue® Hb-301: 90.3%; HemoCue® Hb-801: 93.4%) compared to noninvasive devices (Apple®: 31.5%; Android®: 34.6%; Masimo Pronto®: 49.5%). Sensitivity and specificity were 63.9% and 48.2% for Apple®, 36.1% and 67.6% for Android®, 45.7% and 85.3% for Masimo Pronto®, 54.3% and 97.6% for HemoCue® Hb-301, and 66.7% and 97.6% for HemoCue® Hb-801. Noninvasive devices were considered easy to use and were the preferred method by participants. Among the only studies to compare multiple point-of-care approaches to hemoglobin testing, the diagnostic ability of HemoCue® was comparable to reference hemoglobin, while noninvasive devices had high user acceptability but considerable biases. Improvements in noninvasive device performance and further testing in anemic populations are recommended before broader use.

BACKGROUND: Rising prevalence of overweight/obesity (OWOB) alongside persistent micronutrient deficiencies suggests many women face concomitant OWOB and undernutrition. OBJECTIVES: We aimed to 1) describe the prevalence of the double burden of malnutrition (DBM) among nonpregnant women of reproductive age, defined as intraindividual OWOB and either ≥1 micronutrient deficiency [micronutrient deficiency index (MDI) > 0; DBM-MDI] or anemia (DBM-anemia); 2) test whether the components of the DBM were independent; and 3) identify factors associated with DBM-MDI and DBM-anemia. METHODS: With data from 17 national surveys spanning low- and middle-income countries (LMICs) and high-income countries from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia project (n = 419 to n = 9029), we tested independence of over- and undernutrition using the Rao-Scott chi-square test and examined predictors of the DBM and its components using logistic regression for each survey. RESULTS: Median DBM-MDI was 21.9% (range: 1.6%-39.2%); median DBM-anemia was 8.6% (range: 1.0%-18.6%). OWOB and micronutrient deficiencies or anemia were independent in most surveys. Where associations existed, OWOB was negatively associated with micronutrient deficiencies and anemia in LMICs. In 1 high-income country, OWOB women were more likely to experience micronutrient deficiencies and anemia. Age was consistently positively associated with OWOB and the DBM, whereas the associations with other sociodemographic characteristics varied. Higher socioeconomic status tended to be positively associated with OWOB and the DBM in LMICs, whereas in higher-income countries the association was reversed. CONCLUSIONS: The independence of OWOB and micronutrient deficiencies or anemia within individuals suggests that these forms of over- and undernutrition may have unique etiologies. Decision-makers should still consider the prevalence, consequences, and etiology of the individual components of the DBM as programs move towards double-duty interventions aimed at addressing OWOB and undernutrition simultaneously.

BACKGROUND: Globally, injury deaths largely occur in low- and middle-income countries. No estimates of injury associated mortality exist in Rwanda. This study aimed to describe the patterns of injury-related deaths in Kigali, Rwanda using existing data sources. METHODS: We created a database of all deaths reported by the main institutions providing emergency care in Kigali—four major hospitals, two divisions of the Rwanda National Police, and the National Emergency Medical Service--during 12 months (Jan–Dec 2012) and analyzed it for demographics, diagnoses, mechanism and type of injury, causes of death, and all-cause and cause-specific mortality rates. RESULTS: There were 2682 deaths, 57% in men, 67% in adults >18 year, and 16% in children <5 year. All-cause mortality rate was 236/100,000; 35% (927) were due to probable surgical causes. Injury-related deaths occurred in 22% (593/2682). The most common injury mechanism was road traffic crash (cause-specific mortality rate of 20/100,000). Nearly half of all injury deaths occurred in the prehospital setting (47%, n = 276) and 49% of injury deaths at the university hospital occurred within 24 h of arrival. Being injured increased the odds of dying in the prehospital setting by 2.7 times (p < 0.0001). CONCLUSIONS: Injuries account for 22% of deaths in Kigali with road traffic crashes being the most common cause.Injury deaths occurred largely in the prehospital setting and within the first 24 h of hospital arrival suggesting the need for investment in emergency infrastructure. Accurate documentation of the cause of death would help policy makers make data-driven resource allocation decisions.

Little is known about the specific causes of neonatal and under-five childhood death in high-mortality geographic regions due to a lack of primary data and dependence on inaccurate tools, such as verbal autopsy. To meet the ambitious new Sustainable Development Goal 3.2 to eliminate preventable child mortality in every country, better approaches are needed to precisely determine specific causes of death so that prevention and treatment interventions can be strengthened and focused. Minimally invasive tissue sampling (MITS) is a technique that uses needle-based postmortem sampling, followed by advanced histopathology and microbiology to definitely determine cause of death. The Bill & Melinda Gates Foundation is supporting a new surveillance system called the Child Health and Mortality Prevention Surveillance network, which will determine cause of death using MITS in combination with other information, and yield cause-specific population-based mortality rates, eventually in up to 12-15 sites in sub-Saharan Africa and south Asia. However, the Gates Foundation funding alone is not enough. We call on governments, other funders, and international stakeholders to expand the use of pathology-based cause of death determination to provide the information needed to end preventable childhood mortality.

Abstract In sub-Saharan Africa, inherited causes of anemia are common, but data are limited regarding the geographical prevalence and coinheritance of these conditions and their overall contributions to childhood anemia. To address these questions in Malawi, we performed a secondary analysis of the 2015-2016 Malawi Micronutrient Survey, a nationally and regionally representative survey that estimated the prevalence of micronutrient deficiencies and evaluated both inherited and noninherited determinants of anemia. Children age 6 to 59 months were sampled from 105 clusters within the 2015-2016 Malawi Demographic Health Survey. Hemoglobin, ferritin, retinol binding protein, malaria, and inflammatory biomarkers were measured from venous blood. Molecular studies were performed using dried blood spots to determine the presence of sickle cell disease or trait, α-thalassemia trait, and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Of 1279 eligible children, 1071 were included in the final analysis. Anemia, iron deficiency, and malaria were common, affecting 30.9%, 21.5%, and 27.8% of the participating children, respectively. α-Thalassemia trait was common (&amp;gt;40% of children demonstrating deletion of 1 [33.1%] or 2 [10.0%] α-globin genes) and associated with higher prevalence of anemia (P &amp;lt; .001). Approximately 20% of males had G6PD deficiency, which was associated with a 1.0 g/dL protection in hemoglobin decline during malaria infection (P = .02). These data document that inherited blood disorders are common and likely play an important role in the prevalence of anemia and malaria in Malawian children.

Anaemia is a public health problem in Ghana. We sought to identify factors associated with haemoglobin concentration (Hb) and anaemia among school-attending adolescents. We analysed data from 2948 adolescent girls and 609 boys (10-19 years) selected from 115 schools from regions of Ghana as a secondary analysis of baseline surveys conducted at two time-points. We measured Hb, malaria from capillary blood, anthropometry and used a modified food frequency questionnaire to assess diet. Multivariable linear and Poisson regression models were used to identify predictors of Hb and anaemia. The prevalence of anaemia, malaria and geophagy were 24, 25, and 24 %, respectively, among girls and 13, 27 and 6 %, respectively, among boys. Girls engaging in geophagy had a 53 % higher adjusted prevalence of anaemia and 0⋅39 g/dl lower Hb. There were similar results among those who tested positive for malaria (+52 % anaemia; -0⋅42 g/dl Hb). Among girls, lower anaemia prevalence and higher Hb were associated with consumption of foods rich in haeme iron (-22 %; +0⋅18 g/dl), consumption of iron-fortified cereal/beverages consumed with citrus (-50 %; +0⋅37 g/dl) and being overweight (-22 %; +0⋅22 g/dl). Age was positively associated with anaemia among girls, but negatively associated among boys. Boys who tested positive for malaria had 0⋅31 g/dl lower Hb. Boys who were overweight or had obesity and consumed flour products were also more likely to be anaemic (119 and 56 %, respectively). Factors associated with Hb and anaemia may inform anaemia reduction interventions among school-going adolescents and suggest the need to tailor them uniquely for boys and girls.

Invasive disease caused by Streptococcus pneumoniae (IPD) is one of the leading causes of morbidity and mortality in young children worldwide. In Argentina, PCV13 was introduced into the childhood immunization programme nationwide in 2012 and PCV7 was available from 2000, but only in the private market. Since 1993 the National IPD Surveillance Programme, consisting of 150 hospitals, has conducted nationwide pneumococcal surveillance in Argentina in children under 6 years of age, as part of the SIREVA II-OPS network. A total of 1713 pneumococcal isolates characterized by serotype (Quellung) and antimicrobial resistance (agar dilution) to ten antibiotics, belonging to three study periods: pre-PCV7 era 1998–1999 (pre-PCV), before the introduction of PCV13 2010–2011 (PCV7) and after the introduction of PCV13 2012–2013 (PCV13), were available for inclusion. Fifty-four serotypes were identified in the entire collection and serotypes 14, 5 and 1 represented 50 % of the isolates. Resistance to penicillin was 34.9 %, cefotaxime 10.6 %, meropenem 4.9 %, cotrimoxazole 45 %, erythromycin 21.5 %, tetracycline 15.4 % and chloramphenicol 0.4 %. All the isolates were susceptible to levofloxacin, rifampin and vancomycin. Of 1713 isolates, 1061 (61.9 %) were non-susceptible to at least one antibiotic and 235(13.7 %) were multidrug resistant. A subset of 413 isolates was randomly selected and whole-genome sequenced as part of Global Pneumococcal Sequencing Project (GPS). The genome data was used to investigate the population structure of S. pneumoniae defining pneumococcal lineages using Global Pneumococcal Sequence Clusters (GPSCs), sequence types (STs) and clonal complexes (CCs), prevalent serotypes and their associated pneumococcal lineages and genomic inference of antimicrobial resistance. The collection showed a great diversity of strains. Among the 413 isolates, 73 known and 36 new STs were identified belonging to 38 CCs and 25 singletons, grouped into 52 GPSCs. Important changes were observed among vaccine types when pre-PCV and PCV13 periods were compared; a significant decrease in serotypes 14, 6B and 19F and a significant increase in 7F and 3. Among non-PCV13 types, serogroup 24 increased from 0 % in pre-PCV to 3.2 % in the PCV13 period. Our analysis showed that 66.1 % (273/413) of the isolates were predicted to be non-susceptible to at least one antibiotic and 11.9 % (49/413) were multidrug resistant. We found an agreement of 100 % when comparing the serotype determined by Quellung and WGS-based serotyping and 98.4 % of agreement in antimicrobial resistance. Continued surveillance of the pneumococcal population is needed to reveal the dynamics of pneumococcal isolates in Argentina in post-PCV13. This article contains data hosted by Microreact.

The authors discuss the Emory Global Health Institute, an organization that advances Emory University's global health efforts by providing guidance and financial support to Emory faculty, students, and alumni as they develop and implement global health initiatives. They discuss both the external and internal factors that led to the September 2006 establishment of the institute, as well as Emory's existing global health strengths on which it was founded. These strengths include Emory's schools of medicine, nursing, and public health, which were already deeply engaged in global health work, and Emory's long-standing partnerships with government agencies, nongovernmental organizations, and other academic institutions working on a variety of global health problems. The institute serves as an internal resource for the entire Emory University community as its members work to solve critical global health issues around the world. The authors discuss the institute's vision, mission, goals, activities, and early accomplishments. They also discuss the institute's plans for the future and the challenges they foresee. In addition, the authors emphasize that it is important for academic institutions to establish strong global partnerships. Universities are much more likely to be successful in both launching and sustaining global health programs if they work in a true partnership with people who know firsthand what their health concerns are and how to best address them in their communities. The authors conclude that global health provides an opportunity for academic institutions to put aside their competitive tendencies and work collaboratively to address global health challenges.

BACKGROUND: Anemia is a moderate public health problem among adolescent girls in Ghana. OBJECTIVES: We aimed to evaluate the barriers to and facilitators of program fidelity to a school-based anemia reduction program with weekly iron and folic acid (IFA) supplementation. METHODS: Authors analyzed directly observed weekly IFA consumption data collected longitudinally and cross-sectional data from a representative survey of 60 secondary schools and 1387 adolescent girls in the Northern and Volta regions of Ghana after 1 school year (2017-2018) of the intervention (30-36 wk). A bottleneck analysis was used to characterize the levels of IFA coverage and used adjusted generalized linear mixed-effects models to quantify the school and student drivers of IFA intake adherence. RESULTS: Of girls, 90% had ever consumed the tablet, whereas 56% had consumed ≥15 weekly tablets (mean: 16.4, range: 0-36), indicating average intake adherence was about half of the available tablets. Among ever consumers, 88% of girls liked the tablet, and 27% reported undesirable changes (primarily heavy menstrual flow). School-level factors represented 75% of the variance in IFA consumption over the school year. Total IFA tablets consumed was associated with the ability to make up missed IFA distributions (+1.4 tablets; 95% CI: +0.8, +2.0 tablets), junior compared with senior secondary school (+5.8; 95% CI: +0.1, +11.5), educators' participating in a program-related training (+7.6; 95% CI: +2.9, 12.2), and educator perceptions that implementation was difficult (-6.9; 95% CI: -12.1, -1.7) and was an excessive time burden (-4.4; 95% CI: -8.4, -0.4). CONCLUSIONS: Although the program reached Ghanaian schoolgirls, school-level factors were barriers to adherence. Modifications such as expanded training, formalized make-up IFA distributions, sensitization (awareness promotion), and additional support to senior high schools may improve adherence. Spreading the responsibility for IFA distribution to other teachers and streamlining monitoring may reduce the burden at the school level. Strengthening the health education component and improving knowledge of IFA among students may also be beneficial.

BACKGROUND: Pneumococcal disease outbreaks of vaccine preventable serotype 4 sequence type (ST)801 in shipyards have been reported in several countries. We aimed to use genomics to establish any international links between them. METHODS: Sequence data from ST801-related outbreak isolates from Norway (n = 17), Finland (n = 11) and Northern Ireland (n = 2) were combined with invasive pneumococcal disease surveillance from the respective countries, and ST801-related genomes from an international collection (n = 41 of > 40,000), totalling 106 genomes. Raw data were mapped and recombination excluded before phylogenetic dating. RESULTS: Outbreak isolates were relatively diverse, with up to 100 SNPs (single nucleotide polymorphisms) and a common ancestor estimated around the year 2000. However, 19 Norwegian and Finnish isolates were nearly indistinguishable (0-2 SNPs) with the common ancestor dated around 2017. CONCLUSION: The total diversity of ST801 within the outbreaks could not be explained by recent transmission alone, suggesting that harsh environmental and associated living conditions reported in the shipyards may facilitate invasion of colonising pneumococci. However, near identical strains in the Norwegian and Finnish outbreaks does suggest that transmission between international shipyards also contributed to those outbreaks. This indicates the need for improved preventative measures in this working population including pneumococcal vaccination.

OBJECTIVE: Anonymised patient-level data from clinical research are increasingly recognised as a fundamental and valuable resource. It has value beyond the original research project and can help drive scientific research and innovations and improve patient care. To support responsible data sharing, we need to develop systems that work for all stakeholders. The members of the Independent Review Panel (IRP) for the data sharing platform Clinical Study Data Request (CSDR) describe here some summary metrics from the platform and challenge the research community on why the promised demand for data has not been observed. SUMMARY OF DATA: From 2014 to the end of January 2019, there were a total of 473 research proposals (RPs) submitted to CSDR. Of these, 364 met initial administrative and data availability checks, and the IRP approved 291. Of the 90 research teams that had completed their analyses by January 2018, 41 reported at least one resulting publication to CSDR. Less than half of the studies ever listed on CSDR have been requested. CONCLUSION: While acknowledging there are areas for improvement in speed of access and promotion of the platform, the total number of applications for access and the resulting publications have been low and challenge the sustainability of this model. What are the barriers for data contributors and secondary analysis researchers? If this model does not work for all, what needs to be changed? One thing is clear: that data access can realise new and unforeseen contributions to knowledge and improve patient health, but this will not be achieved unless we build sustainable models together that work for all.

BACKGROUND: Kenya introduced 10-valent pneumococcal conjugate vaccine (PCV10) among children <1 year in 2011 with catch-up vaccination among children 1-4 years in some areas. We assessed changes in pneumococcal carriage and antibiotic susceptibility patterns in children <5 years and adults. METHODS: During 2009-2013, we performed annual cross-sectional pneumococcal carriage surveys in 2 sites: Kibera (children <5 years) and Lwak (children <5 years, adults). Only Lwak had catch-up vaccination. Nasopharyngeal and oropharyngeal (adults only) swabs underwent culture for pneumococci; isolates were serotyped. Antibiotic susceptibility testing was performed on isolates from 2009 and 2013; penicillin nonsusceptible pneumococci (PNSP) was defined as penicillin-intermediate or -resistant. Changes in pneumococcal carriage by age (<1 year, 1-4 years, adults), site, and human immunodeficiency virus (HIV) status (adults only) were calculated using modified Poisson regression, with 2009-2010 as baseline. RESULTS: We enrolled 2962 children (2073 in Kibera, 889 in Lwak) and 2590 adults (2028 HIV+, 562 HIV-). In 2013, PCV10-type carriage was 10.3% (Lwak) to 14.6% (Kibera) in children <1 year and 13.8% (Lwak) to 18.7% (Kibera) in children 1-4 years. This represents reductions of 60% and 63% among children <1 year and 52% and 60% among children 1-4 years in Kibera and Lwak, respectively. In adults, PCV10-type carriage decreased from 12.9% to 2.8% (HIV+) and from 11.8% to 0.7% (HIV-). Approximately 80% of isolates were PNSP, both in 2009 and 2013. CONCLUSIONS: PCV10-type carriage declined in children <5 years and adults post-PCV10 introduction. However, PCV10-type and PNSP carriage persisted in children regardless of catch-up vaccination.

Science based and often relatively apolitical, they deserve 10% of donors' funds

Pneumococcal serotype 35B is an important non-conjugate vaccine (non-PCV) serotype. Its continued emergence, post-PCV7 in the USA, was associated with expansion of a pre-existing 35B clone (clonal complex [CC] 558) along with post-PCV13 emergence of a non-35B clone previously associated with PCV serotypes (CC156). This study describes lineages circulating among 35B isolates in South Africa before and after PCV introduction. We also compared 35B isolates belonging to a predominant 35B lineage in South Africa (GPSC5), with isolates belonging to the same lineage in other parts of the world. Serotype 35B isolates that caused invasive pneumococcal disease in South Africa in 2005-2014 were characterized by whole-genome sequencing (WGS). Multi-locus sequence types and global pneumococcal sequence clusters (GPSCs) were derived from WGS data of 63 35B isolates obtained in 2005-2014. A total of 262 isolates that belong to GPSC5 (115 isolates from South Africa and 147 from other countries) that were sequenced as part of the global pneumococcal sequencing (GPS) project were included for comparison. Serotype 35B isolates from South Africa were differentiated into seven GPSCs and GPSC5 was most common (49 %, 31/63). While 35B was the most common serotype among GPSC5/CC172 isolates in South Africa during the PCV13 period (66 %, 29/44), 23F was the most common serotype during both the pre-PCV (80 %, 37/46) and PCV7 period (32 %, 8/25). Serotype 35B represented 15 % (40/262) of GPSC5 isolates within the global GPS database and 75 % (31/40) were from South Africa. The predominance of the GPSC5 lineage within non-vaccine serotype 35B, is possibly unique to South Africa and warrants further molecular surveillance of pneumococci.