Dataset Information

Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical model-based map and population estimates.

ABSTRACT: Reliable estimates of populations affected by diseases are necessary to guide efficient allocation of public health resources. Sickle haemoglobin (HbS) is the most common and clinically significant haemoglobin structural variant, but no contemporary estimates exist of the global populations affected. Moreover, the precision of available national estimates of heterozygous (AS) and homozygous (SS) neonates is unknown. We aimed to provide evidence-based estimates at various scales, with uncertainty measures.Using a database of sickle haemoglobin surveys, we created a contemporary global map of HbS allele frequency distribution within a Bayesian geostatistical model. The pairing of this map with demographic data enabled calculation of global, regional, and national estimates of the annual number of AS and SS neonates. Subnational estimates were also calculated in data-rich areas.Our map shows subnational spatial heterogeneities and high allele frequencies across most of sub-Saharan Africa, the Middle East, and India, as well as gene flow following migrations to western Europe and the eastern coast of the Americas. Accounting for local heterogeneities and demographic factors, we estimated that the global number of neonates affected by HbS in 2010 included 5,476,000 (IQR 5,291,000-5,679,000) AS neonates and 312,000 (294,000-330,000) SS neonates. These global estimates are higher than previous conservative estimates. Important differences predicted at the national level are discussed.HbS will have an increasing effect on public health systems. Our estimates can help countries and the international community gauge the need for appropriate diagnoses and genetic counselling to reduce the number of neonates affected. Similar mapping and modelling methods could be used for other inherited disorders.The Wellcome Trust.

SUBMITTER: Piel FB

PROVIDER: S-EPMC3547249 | biostudies-other | 2013 Jan

REPOSITORIES: biostudies-other

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Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical model-based map and population estimates.

Piel Frédéric B FB Patil Anand P AP Howes Rosalind E RE Nyangiri Oscar A OA Gething Peter W PW Dewi Mewahyu M Temperley William H WH Williams Thomas N TN Weatherall David J DJ Hay Simon I SI

Lancet (London, England) 20121025 9861

<h4>Background</h4>Reliable estimates of populations affected by diseases are necessary to guide efficient allocation of public health resources. Sickle haemoglobin (HbS) is the most common and clinically significant haemoglobin structural variant, but no contemporary estimates exist of the global populations affected. Moreover, the precision of available national estimates of heterozygous (AS) and homozygous (SS) neonates is unknown. We aimed to provide evidence-based estimates at various scale ...[more]

PMID: 23103089

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Project description:BackgroundChanges in the geographical distribution of genetic disorders are often thought to happen slowly, especially when compared with infectious diseases. Whereas mutations, genetic drift, and natural selection take place over many generations, epidemics can spread through large populations within a few days or weeks. Nevertheless, population movements can interfere with these processes, and few studies have been done of their eff ect on genetic disorders. We aimed to investigate the eff ect of global migration on the distribution of the sickle-cell gene-the most common and clinically significant haemoglobin structural variant.MethodsFor each country, we extracted data from the World Bank’s Global Bilateral Migration Database about international human migrations between 1960 and 2000. We combined this information with evidence-based estimates of national HbS allele frequencies, generated within a Bayesian geostatistical framework, to analyse temporal changes in the net numbers of migrants, and classified countries with an index summarising these temporal trends.FindingsThe number of international migrants increased from 92.6 million in 1960, to 165.2 million in 2000. The estimated global number of migrants with HbS increased from about 1.6 million in 1960, to 3.6 million in 2000. This increase was largely due to an increase in the number of migrants from countries with HbS allele frequencies higher than 10%, from 3.1 million in 1960, to 14.2 million in 2000. Additionally, the mean number of countries of origin for each destination country increased from 70 (SE 46) in 1960, to 98 (48) in 2000, showing an increasing diversity in the network of international migrations between countries. Our index of change map shows a patchy distribution of the magnitude of temporal changes, with the highest positive and negative values scattered across all continents.InterpretationGlobal human population movements have had a substantial eff ect on the distribution of the HbS gene. Population movements can create a long-term burden on health-care systems. Our findings, which emphasise countries in which migration fluxes are changing the most, should increase awareness about the global burden of haemoglobinopathies and encourage policy makers to implement specific public health interventions, such as screening programmes and genetic counselling.FundingWellcome Trust, European Research Council, Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases-National Institutes of Health, the Research and Policy for Infectious Disease Dynamics program, Fogarty International Center.

Project description:IntroductionThe pharmacokinetics of vancomycin are highly variable among neonates, which makes dosing challenging in this population. However, adequate drug exposure is critical, especially when treating methicillin-resistant Staphylococcus aureus (MRSA) infections. Utilization of population pharmacokinetic models and Bayesian methods offers the potential for developing individualized therapeutic approaches. To meet this need, a neonatal vancomycin population pharmacokinetic model was recently published. The current study sought to externally evaluate the predictive performance and generalizability of this model.MethodsA retrospective chart review of neonates who received vancomycin and had ≥1 peak and ≥1 trough concentrations at five Intermountain Healthcare neonatal intensive care units from 2006 to 2013 was performed and served as the external validation cohort. The published population pharmacokinetic model was implemented in NONMEM 7.2 with the structural and variance parameter values set equal to the estimates reported previously. The model was then used to predict the first peak and trough concentration for each neonate in the validation cohort and the model prediction error and absolute prediction error were calculated. Normalized prediction distribution errors (NPDE) were also evaluated.ResultsA total of 243 neonates were studied with a median postmenstrual age of 33 (range: 23-54) weeks and a median weight of 1.6 (range: 0.4-6.8) kg. The model predicted the observed vancomycin concentrations with reasonable precision. For all vancomycin concentrations, the median prediction error was -0.8 (95% CI: -1.4 to -0.4) mg/L and the median absolute prediction error was 3.0 (95% CI: 2.7-3.5) mg/L. No trends in NPDE across weight, postmenstrual age, serum creatinine, or time after dose were observed.ConclusionAn evaluation of a recently published neonatal vancomycin population pharmacokinetic model in a large external dataset supported the predictive performance and generalizability of the model. This model may be useful in evaluating neonatal vancomycin dosing regimens and estimating the extent of drug exposure.

Dataset Information

Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical model-based map and population estimates.

Publications

Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical model-based map and population estimates.

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