National, regional, and global estimates of anaemia by severity in women and children for 2000-19: a pooled analysis of population-representative data

BACKGROUND: Anaemia causes health and economic harms. The prevalence of anaemia in women aged 15-49 years, by pregnancy status, is indicator 2.2.3 of the UN Sustainable Development Goals, and the aim of halving the anaemia prevalence in women of reproductive age by 2030 is an extension of the 2025 global nutrition targets endorsed by the World Health Assembly (WHA). We aimed to estimate the prevalence of anaemia by severity for children aged 6-59 months, non-pregnant women aged 15-49 years, and pregnant women aged 15-49 years in 197 countries and territories and globally for the period 2000-19. METHODS: For this pooled analysis of population-representative data, we collated 489 data sources on haemoglobin distribution in children and women from 133 countries, including 4·5 million haemoglobin measurements. Our data sources comprised health examination, nutrition, and household surveys, accessed as anonymised individual records or as summary statistics such as mean haemoglobin and anaemia prevalence. We used a Bayesian hierarchical mixture model to estimate haemoglobin distributions in each population and country-year. This model allowed for coherent estimation of mean haemoglobin and prevalence of anaemia by severity. FINDINGS: Globally, in 2019, 40% (95% uncertainty interval [UI] 36-44) of children aged 6-59 months were anaemic, compared to 48% (45-51) in 2000. Globally, the prevalence of anaemia in non-pregnant women aged 15-49 years changed little between 2000 and 2019, from 31% (95% UI 28-34) to 30% (27-33), while in pregnant women aged 15-49 years it decreased from 41% (39-43) to 36% (34-39). In 2019, the prevalence of anaemia in children aged 6-59 months exceeded 70% in 11 countries and exceeded 50% in all women aged 15-49 years in ten countries. Globally in all populations and in most countries and regions, the prevalence of mild anaemia changed little, while moderate and severe anaemia declined in most populations and geographical locations, indicating a shift towards mild anaemia. INTERPRETATION: Globally, regionally, and in nearly all countries, progress on anaemia in women aged 15-49 years is insufficient to meet the WHA global nutrition target to halve anaemia prevalence by 2030, and the prevalence of anaemia in children also remains high. A better understanding of the context-specific causes of anaemia and quality implementation of effective multisectoral actions to address these causes are needed. FUNDING: USAID, US Centers for Disease Control and Prevention, and Bill & Melinda Gates Foundation

The effectiveness and complexity of interventions targeting sedentary behaviour across the lifespan: a systematic review and meta-analysis

Background: Evidence suggests that sedentary behaviour (SB) is associated with poor health outcomes. SB at any age may have significant consequences for health and well-being and interventions targeting SB are accumulating. Therefore, the need to review the effects of multicomponent, complex interventions that incorporate effective strategies to reduce SB are essential. Methods: A systematic review and meta-analysis were conducted investigating the impact of interventions targeting SB across the lifespan. Six databases were searched and two review authors independently screened studies for eligibility, completed data extraction and assessed the risk of bias and complexity of each of the included studies. Results: A total of 77 adult studies (n=62, RCTs) and 84 studies (n=62, RCTs) in children were included. The findings demonstrated that interventions in adults when compared to active controls resulted in non-significant reductions in SB, although when compared to inactive controls significant reductions were found in both the short (MD -56.86; 95%CI -74.10, -39.63; n=4632; I2 83%) and medium-to-long term (MD -20.14; 95%CI -34.13, -6.16; n=4537; I2 65%). The findings demonstrated that interventions in children when compared to active controls may lead to relevant reductions in daily sedentary time in the short-term (MD -59.90; 95%CI -102.16, -17.65; n=267; I2 86%), while interventions in children when compared to inactive controls may lead to relevant reductions in the short-term (MD -25.86; 95%CI -40.77, -10.96; n=9480; I2 98%) and medium-to-long term (MD -14.02; 95%CI -19.49, -8.55; n=41,138; I2 98%). The assessment of complexity suggested that interventions may need to be suitably complex to address the challenges of a complex behaviour such as SB, but demonstrated that a higher complexity score is not necessarily associated with better outcomes in terms of sustained long-term changes. Conclusions: Interventions targeting reductions in SB have been shown to be successful, especially environmental interventions in both children and adults. More needs to be known about how best to optimise intervention effects. Future intervention studies should apply more rigorous methods to improve research quality, considering larger sample sizes, randomised controlled designs and valid and reliable measures of SB

Cabozantinib in progressive medullary thyroid cancer

Purpose Cabozantinib, a tyrosine kinase inhibitor (TKI) of hepatocyte growth factor receptor (MET), vascular endothelial growth factor receptor 2, and rearranged during transfection (RET), demonstrated clinical activity in patients with medullary thyroid cancer (MTC) in phase I. Patients and Methods We conducted a double-blind, phase III trial comparing cabozantinib with placebo in 330 patients with documented radiographic progression of metastatic MTC. Patients were randomly assigned (2:1) to cabozantinib (140 mg per day) or placebo. The primary end point was progression-free survival (PFS). Additional outcome measures included tumor response rate, overall survival, and safety. Results The estimated median PFS was 11.2 months for cabozantinib versus 4.0 months for placebo (hazard ratio, 0.28; 95% CI, 0.19 to 0.40; P < .001). Prolonged PFS with cabozantinib was observed across all subgroups including by age, prior TKI treatment, and RET mutation status (hereditary or sporadic). Response rate was 28% for cabozantinib and 0% for placebo; responses were seen regardless of RET mutation status. Kaplan-Meier estimates of patients alive and progression-free at 1 year are 47.3% for cabozantinib and 7.2% for placebo. Common cabozantinib-associated adverse events included diarrhea, palmar-plantar erythrodysesthesia, decreased weight and appetite, nausea, and fatigue and resulted in dose reductions in 79% and holds in 65% of patients. Adverse events led to treatment discontinuation in 16% of cabozantinib-treated patients and in 8% of placebo-treated patients. Conclusion Cabozantinib (140 mg per day) achieved a statistically significant improvement of PFS in patients with progressive metastatic MTC and represents an important new treatment option for patients with this rare disease. This dose of cabozantinib was associated with significant but manageable toxicity

Morphological characteristics of motor neurons do not determine their relative susceptibility to degeneration in a mouse model of severe spinal muscular atrophy

Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality, resulting primarily from the degeneration and loss of lower motor neurons. Studies using mouse models of SMA have revealed widespread heterogeneity in the susceptibility of individual motor neurons to neurodegeneration, but the underlying reasons remain unclear. Data from related motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), suggest that morphological properties of motor neurons may regulate susceptibility: in ALS larger motor units innervating fast-twitch muscles degenerate first. We therefore set out to determine whether intrinsic morphological characteristics of motor neurons influenced their relative vulnerability to SMA. Motor neuron vulnerability was mapped across 10 muscle groups in SMA mice. Neither the position of the muscle in the body, nor the fibre type of the muscle innervated, influenced susceptibility. Morphological properties of vulnerable and disease-resistant motor neurons were then determined from single motor units reconstructed in Thy.1-YFP-H mice. None of the parameters we investigated in healthy young adult mice - including motor unit size, motor unit arbor length, branching patterns, motor endplate size, developmental pruning and numbers of terminal Schwann cells at neuromuscular junctions - correlated with vulnerability. We conclude that morphological characteristics of motor neurons are not a major determinant of disease-susceptibility in SMA, in stark contrast to related forms of motor neuron disease such as ALS. This suggests that subtle molecular differences between motor neurons, or extrinsic factors arising from other cell types, are more likely to determine relative susceptibility in SMA

Intra- and inter-individual genetic differences in gene expression

Genetic variation is known to influence the amount of mRNA produced by a gene. Given that the molecular machines control mRNA levels of multiple genes, we expect genetic variation in the components of these machines would influence multiple genes in a similar fashion. In this study we show that this assumption is correct by using correlation of mRNA levels measured independently in the brain, kidney or liver of multiple, genetically typed, mice strains to detect shared genetic influences. These correlating groups of genes (CGG) have collective properties that account for 40-90% of the variability of their constituent genes and in some cases, but not all, contain genes encoding functionally related proteins. Critically, we show that the genetic influences are essentially tissue specific and consequently the same genetic variations in the one animal may up-regulate a CGG in one tissue but down-regulate the same CGG in a second tissue. We further show similarly paradoxical behaviour of CGGs within the same tissues of different individuals. The implication of this study is that this class of genetic variation can result in complex inter- and intra-individual and tissue differences and that this will create substantial challenges to the investigation of phenotypic outcomes, particularly in humans where multiple tissues are not readily available.&#xd;&#xa;&#xd;&#xa

Achieving high coverage of larval-stage mosquito surveillance: challenges for a community-based mosquito control programme in urban Dar es Salaam, Tanzania

BACKGROUND\ud \ud Preventing malaria by controlling mosquitoes in their larval stages requires regular sensitive monitoring of vector populations and intervention coverage. The study assessed the effectiveness of operational, community-based larval habitat surveillance systems within the Urban Malaria Control Programme (UMCP) in urban Dar es Salaam, Tanzania.\ud \ud METHODS\ud \ud Cross-sectional surveys were carried out to assess the ability of community-owned resource persons (CORPs) to detect mosquito breeding sites and larvae in areas with and without larviciding. Potential environmental and programmatic determinants of habitat detection coverage and detection sensitivity of mosquito larvae were recorded during guided walks with 64 different CORPs to assess the accuracy of data each had collected the previous day.\ud \ud RESULTS\ud \ud CORPs reported the presence of 66.2% of all aquatic habitats (1,963/2,965), but only detected Anopheles larvae in 12.6% (29/230) of habitats that contained them. Detection sensitivity was particularly low for late-stage Anopheles (2.7%, 3/111), the most direct programmatic indicator of malaria vector productivity. Whether a CORP found a wet habitat or not was associated with his/her unfamiliarity with the area (Odds Ratio (OR) [95% confidence interval (CI)] = 0.16 [0.130, 0.203], P < 0.001), the habitat type (P < 0.001) or a fence around the compound (OR [95%CI] = 0.50 [0.386, 0.646], P < 0.001). The majority of mosquito larvae (Anophelines 57.8% (133/230) and Culicines 55.9% (461/825) were not reported because their habitats were not found. The only factor affecting detection of Anopheline larvae in habitats that were reported by CORPs was larviciding, which reduced sensitivity (OR [95%CI] = 0.37 [0.142, 0.965], P = 0.042).\ud \ud CONCLUSIONS\ud \ud Accessibility of habitats in urban settings presents a major challenge because the majority of compounds are fenced for security reasons. Furthermore, CORPs under-reported larvae especially where larvicides were applied. This UMCP system for larval surveillance in cities must be urgently revised to improve access to enclosed compounds and the sensitivity with which habitats are searched for larvae

Recent acquisition of Helicobacter pylori by Baka Pygmies

Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and most divergent population, hpAfrica2, evolved within San hunter-gatherers, who represent one of the deepest branches of the human population tree. Anticipating the presence of ancient H. pylori lineages within all hunter-gatherer populations, we investigated the prevalence and population structure of H. pylori within Baka Pygmies in Cameroon. Gastric biopsies were obtained by esophagogastroduodenoscopy from 77 Baka from two geographically separated populations, and from 101 non-Baka individuals from neighboring agriculturalist populations, and subsequently cultured for H. pylori. Unexpectedly, Baka Pygmies showed a significantly lower H. pylori infection rate (20.8%) than non-Baka (80.2%). We generated multilocus haplotypes for each H. pylori isolate by DNA sequencing, but were not able to identify Baka-specific lineages, and most isolates in our sample were assigned to hpNEAfrica or hpAfrica1. The population hpNEAfrica, a marker for the expansion of the Nilo-Saharan language family, was divided into East African and Central West African subpopulations. Similarly, a new hpAfrica1 subpopulation, identified mainly among Cameroonians, supports eastern and western expansions of Bantu languages. An age-structured transmission model shows that the low H. pylori prevalence among Baka Pygmies is achievable within the timeframe of a few hundred years and suggests that demographic factors such as small population size and unusually low life expectancy can lead to the eradication of H. pylori from individual human populations. The Baka were thus either H. pylori-free or lost their ancient lineages during past demographic fluctuations. Using coalescent simulations and phylogenetic inference, we show that Baka almost certainly acquired their extant H. pylori through secondary contact with their agriculturalist neighbors

Examining the human infectious reservoir for Plasmodium falciparum malaria in areas of differing transmission intensity.

A detailed understanding of the human infectious reservoir is essential for improving malaria transmission-reducing interventions. Here we report a multi-regional assessment of population-wide malaria transmission potential based on 1209 mosquito feeding assays in endemic areas of Burkina Faso and Kenya. Across both sites, we identified 39 infectious individuals. In high endemicity settings, infectious individuals were identifiable by research-grade microscopy (92.6%; 25/27), whilst one of three infectious individuals in the lowest endemicity setting was detected by molecular techniques alone. The percentages of infected mosquitoes in the different surveys ranged from 0.05 (4/7716) to 1.6% (121/7749), and correlate positively with transmission intensity. We also estimated exposure to malaria vectors through genetic matching of blood from 1094 wild-caught bloodfed mosquitoes with that of humans resident in the same houses. Although adults transmitted fewer parasites to mosquitoes than children, they received more mosquito bites, thus balancing their contribution to the infectious reservoir

Mapping of Mycobacterium tuberculosis Complex Genetic Diversity Profiles in Tanzania and Other African Countries

The aim of this study was to assess and characterize Mycobacterium tuberculosis complex (MTBC) genotypic diversity in Tanzania, as well as in neighbouring East and other several African countries. We used spoligotyping to identify a total of 293 M. tuberculosis clinical isolates (one isolate per patient) collected in the Bunda, Dar es Salaam, Ngorongoro and Serengeti areas in Tanzania. The results were compared with results in the SITVIT2 international database of the Pasteur Institute of Guadeloupe. Genotyping and phylogeographical analyses highlighted the predominance of the CAS, T, EAI, and LAM MTBC lineages in Tanzania. The three most frequent Spoligotype International Types (SITs) were: SIT21/CAS1-Kili (n = 76; 25.94%), SIT59/LAM11-ZWE (n = 22; 7.51%), and SIT126/EAI5 tentatively reclassified as EAI3-TZA (n = 18; 6.14%). Furthermore, three SITs were newly created in this study (SIT4056/EAI5 n = 2, SIT4057/T1 n = 1, and SIT4058/EAI5 n = 1). We noted that the East-African-Indian (EAI) lineage was more predominant in Bunda, the Manu lineage was more common among strains isolated in Ngorongoro, and the Central-Asian (CAS) lineage was more predominant in Dar es Salaam (p-value<0.0001). No statistically significant differences were noted when comparing HIV status of patients vs. major lineages (p-value = 0.103). However, when grouping lineages as Principal Genetic Groups (PGG), we noticed that PGG2/3 group (Haarlem, LAM, S, T, and X) was more associated with HIV-positive patients as compared to PGG1 group (Beijing, CAS, EAI, and Manu) (p-value = 0.03). This study provided mapping of MTBC genetic diversity in Tanzania (containing information on isolates from different cities) and neighbouring East African and other several African countries highlighting differences as regards to MTBC genotypic distribution between Tanzania and other African countries. This work also allowed underlining of spoligotyping patterns tentatively grouped within the newly designated EAI3-TZA lineage (remarkable by absence of spacers 2 and 3, and represented by SIT126) which seems to be specific to Tanzania. However, further genotyping information would be needed to confirm this specificity

Older Adults’ Experiences of a Physical Activity and Sedentary Behaviour Intervention: A Nested Qualitative Study in the SITLESS Multi-Country Randomised Clinical Trial

Background: The SITLESS programme comprises exercise referral schemes and self-management strategies and has been evaluated in a trial in Denmark, Spain, Germany and Northern Ireland. The aim of this qualitative study was to understand the implementation and contextual aspects of the intervention in relation to the mechanisms of impact and to explore the perceived effects. Methods: Qualitative methodologies were nested in the SITLESS trial including 71 individual interviews and 12 focus groups targeting intervention and control group participants from postintervention to 18-month follow-up in all intervention sites based on a semi-structured topic guide. Results: Overarching themes were identified under the framework categories of context, implementation, mechanisms of impact and perceived effects. The findings highlight the perceived barriers and facilitators to older adults’ engagement in exercise referral schemes. Social interaction and enjoyment through the group-based programmes are key components to promote adherence and encourage the maintenance of targeted behaviours through peer support and connectedness. Exit strategies and signposting to relevant classes and facilities enabled the maintenance of positive lifestyle behaviours. Conclusions: When designing and implementing interventions, key components enhancing social interaction, enjoyment and continuity should be in place in order to successfully promote sustained behaviour change