Distributional cost-effectiveness analysis in low- and middle-income countries: illustrative example of rotavirus vaccination in Ethiopia

Reducing health inequality is a major policy concern for low- and middle-income countries (LMICs) on the path to universal health coverage. However, health inequality impacts are rarely quantified in cost-effectiveness analyses of health programmes. Distributional cost-effectiveness analysis (DCEA) is a method developed to analyse the expected social distributions of costs and health benefits, and the potential trade-offs that may exist between maximising total health and reducing health inequality. This is the first paper to show how DCEA can be applied in LMICs. Using the introduction of rotavirus vaccination in Ethiopia as an illustrative example, we analyse a hypothetical re-designed vaccination programme, which invests additional resources into vaccine delivery in rural areas, and compare this with the standard programme currently implemented in Ethiopia. We show that the re-designed programme has an incremental cost-effectiveness ratio of US$69 per health-adjusted life year (HALY) compared with the standard programme. This is potentially cost-ineffective when compared with current estimates of health opportunity cost in Ethiopia. However, rural populations are typically less wealthy than urban populations and experience poorer lifetime health. Prioritising such populations can thus be seen as being equitable. We analyse the trade-off between cost-effectiveness and equity using the Atkinson inequality aversion parameter, ε , representing the decision maker’s strength of concern for reducing health inequality. We find that the more equitable programme would be considered worthwhile by a decision maker whose inequality concern is greater than ε = 5.66, which at current levels of health inequality in Ethiopia implies that health gains are weighted at least 3.86 times more highly in the poorest compared with the richest wealth quintile group. We explore the sensitivity of this conclusion to a range of assumptions and cost-per-HALY threshold values, to illustrate how DCEA can inform the thinking of decision makers and stakeholders about health equity trade-offs

A Combined Pulmonary Function and Emphysema Score Prognostic Index for Staging in Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) is characterized by high morbidity and mortality. Lung computed tomography parameters, individually or as part of a composite index, may provide more prognostic information than pulmonary function tests alone.To investigate the prognostic value of emphysema score and pulmonary artery measurements compared with lung function parameters in COPD and construct a prognostic index using a contingent staging approach.Predictors of mortality were assessed in COPD outpatients whose lung computed tomography, spirometry, lung volumes and gas transfer data were collected prospectively in a clinical database. Univariate and multivariate Cox proportional hazard analysis models with bootstrap techniques were used.169 patients were included (59.8% male, 61.1 years old; Forced Expiratory Volume in 1 second % predicted: 40.5±19.2). 20.1% died; mean survival was 115.4 months. Age (HR = 1.098, 95% Cl = 1.04-1.252) and emphysema score (HR = 1.034, 95% CI = 1.007-1.07) were the only independent predictors of mortality. Pulmonary artery dimensions were not associated with survival. An emphysema score of 55% was chosen as the optimal threshold and 30% and 65% as suboptimals. Where emphysema score was between 30% and 65% (intermediate risk) the optimal lung volume threshold, a functional residual capacity of 210% predicted, was applied. This contingent staging approach separated patients with an intermediate risk based on emphysema score alone into high risk (Functional Residual Capacity ≥210% predicted) or low risk (Functional Residual Capacity <210% predicted). This approach was more discriminatory for survival (HR = 3.123; 95% CI = 1.094-10.412) than either individual component alone.Although to an extent limited by the small sample size, this preliminary study indicates that the composite Emphysema score-Functional Residual Capacity index might provide a better separation of high and low risk patients with COPD, than other individual predictors alone

Cheating on the Edge

We present the results of an individual agent-based model of antibiotic resistance in bacteria. Our model examines antibiotic resistance when two strategies exist: “producers”–who secrete a substance that breaks down antibiotics–and nonproducers (“cheats”) who do not secrete, or carry the machinery associated with secretion. The model allows for populations of up to 10,000, in which bacteria are affected by their nearest neighbors, and we assume cheaters die when there are no producers in their neighborhood. Each of 10,000 slots on our grid (a torus) could be occupied by a producer or a nonproducer, or could (temporarily) be unoccupied. The most surprising and dramatic result we uncovered is that when producers and nonproducers coexist at equilibrium, nonproducers are almost always found on the edges of clusters of producers

Genomic plasticity of the MHC class I A region in rhesus macaques: extensive haplotype diversity at the population level as revealed by microsatellites

The Mamu-A genes of the rhesus macaque show different degrees of polymorphism, transcription level variation, and differential haplotype distribution. Per haplotype, usually one “major” transcribed gene is present, A1 (A7), in various combinations with “minor” genes, A2 to A6. In silico analysis of the physical map of a heterozygous animal revealed the presence of similar Mamu-A regions consisting of four duplication units, but with dissimilar positions of the A1 genes on both haplotypes, and in combination with different minor genes. Two microsatellites, D6S2854 and D6S2859, have been selected as potential tools to characterize this complex region. Subsequent analysis of a large breeding colony resulted in the description of highly discriminative patterns, displaying copy number variation in concert with microsatellite repeat length differences. Sequencing and segregation analyses revealed that these patterns are unique for each Mamu-A haplotype. In animals of Indian, Burmese, and Chinese origin, 19, 15, or 9 haplotypes, respectively, could be defined, illustrating the occurrence of differential block duplications and subsequent rearrangements by recombination. The haplotypes can be assigned to 12 unique combinations of genes (region configurations). Although most configurations harbor two transcribed A genes, one or three genes per haplotype are also present. Additionally, haplotypes lacking an A1 gene or with an A1 duplication appear to exist. The presence of different transcribed A genes/alleles in monkeys from various origins may have an impact on differential disease susceptibilities. The high-throughput microsatellite technique will be a valuable tool in animal selection for diverse biomedical research projects

Possible evidence for a variant of myasthenia gravis based on HLA and acetylcholine receptor antibody in Chinese patients

A comprehensive study of 194 Chinese patients with myasthenia gravis in Hong Kong has shown distinct differences from the patterns of disease seen in Caucasians. Restricted ocular myasthenia is the predominant disease type in patients presenting in the first two decades of life and is associated with absence or low titres of acetylcholine receptor antibody. Predisposition to this type of disease is strongly associated with HLA-DRw9. Generalized myasthenia gravis occurs predominantly in patients presenting after the age of 20 years and is accompanied by high titres of acetylcholine receptor antibody but is less strongly associated with HLA-DRw9. It is suggested that myasthenia gravis occurring within the first two decades of life and characterized by affected ocular muscles and absence or low titre of acetylcholine receptor antibody is a genetically determined variant of the disease which occurs commonly in Orientals.link_to_subscribed_fulltex