The Cost-Effectiveness of Intermittent Preventive Treatment for Malaria in Infants in Sub-Saharan Africa

Background

Intermittent preventive treatment in infants (IPTi) has been shown to decrease clinical malaria by approximately 30% in the first year of life and is a promising malaria control strategy for Sub-Saharan Africa which can be delivered alongside the Expanded Programme on Immunisation (EPI). To date, there have been limited data on the cost-effectiveness of this strategy using sulfadoxine pyrimethamine (SP) and no published data on cost-effectiveness using other antimalarials.

Methods

We analysed data from 5 countries in sub-Saharan Africa using a total of 5 different IPTi drug regimens; SP, mefloquine (MQ), 3 days of chlorproguanil-dapsone (CD), SP plus 3 days of artesunate (SP-AS3) and 3 days of amodiaquine-artesunate (AQ3-AS3).The cost per malaria episode averted and cost per Disability-Adjusted Life-Year (DALY) averted were modeled using both trial specific protective efficacy (PE) for all IPTi drugs and a pooled PE for IPTi with SP, malaria incidence, an estimated malaria case fatality rate of 1.57%, IPTi delivery costs and country specific provider and household malaria treatment costs.

Findings

In sites where IPTi had a significant effect on reducing malaria, the cost per episode averted for IPTi-SP was very low, USD 1.36–4.03 based on trial specific data and USD 0.68–2.27 based on the pooled analysis. For IPTi using alternative antimalarials, the lowest cost per case averted was for AQ3-AS3 in western Kenya (USD 4.62) and the highest was for MQ in Korowge, Tanzania (USD 18.56). Where efficacious, based only on intervention costs, IPTi was shown to be cost effective in all the sites and highly cost-effective in all but one of the sites, ranging from USD 2.90 (Ifakara, Tanzania with SP) to USD 39.63 (Korogwe, Tanzania with MQ) per DALY averted. In addition, IPTi reduced health system costs and showed significant savings to households from malaria cases averted. A threshold analysis showed that there is room for the IPTi-efficacy to fall and still remain highly cost effective in all sites where IPTi had a statistically significant effect on clinical malaria.

Conclusions

IPTi delivered alongside the EPI is a highly cost effective intervention against clinical malaria with a range of drugs in a range of malaria transmission settings. Where IPTi did not have a statistically significant impact on malaria, generally in low transmission sites, it was not cost effective.     

Imaging pancreatic beta-cells in the intact pancreas

We have developed a method to visualize fluorescent protein-labeled beta-cells in the intact pancreas through combined reflection and confocal imaging. This method provides a 3-D view of the beta-cells in situ. Imaging of the pancreas from mouse insulin I promoter (MIP)-green (GFP) and red fluorescent protein (RFP) transgenic mice shows that islets, beta-cell clusters, and single beta-cells are not evenly distributed but are aligned along the large blood vessels. We also observe the solitary beta-cells in both fetal and adult mice and along the pancreatic and common bile ducts. We have imaged the developing endocrine cells in the embryos using neurogenin-3 (Ngn3)-GFP mice crossed with MIP-RFP mice. The dual-color-coded pancreas from embryos (E15.5) shows a large number of green Ngn3-expressing proendocrine cells with a smaller number of red beta-cells. The imaging technique that we have developed, coupled with the transgenic mice in which beta-cells and beta-cell progenitors are labeled with different fluorescent proteins, will be useful for studying pancreatic development and function in normal and disease states.     

SNaPaer: A Practical Single Nucleotide Polymorphism Multiplex Assay for Genotyping of Pseudomonas aeruginosa

Multilocus sequence typing (MLST) represents the gold standard genotyping method in studies concerning microbial population structure, being particularly helpful in the detection of clonal relatedness. However, its applicability on large-scale genotyping is limited due to the high cost and time spent on the task. The selection of the most informative nucleotide positions simplifies genomic characterization of bacteria. A simple and informative multiplex, SNaPaer assay, was developed and genotyping of Pseudomonas aeruginosa was obtained after a single reaction of multiplex PCR amplification and mini-sequencing. This cost-effective technique allowed the analysis of a Portuguese set of isolates (n = 111) collected from three distinct hospitals and the genotyping data could be obtained in less than six hours. Point mutations were shown to be the most frequent event responsible for diversification of the Portuguese population sample. The Portuguese isolates corroborated the epidemic hypothesis for P. aeruginosa population. SNaPaer genotyping assay provided a discriminatory power of 0.9993 for P. aeruginosa, by testing in silico several hundreds of MLST profiles available online. The newly proposed assay targets less than 0.01% of the total MLST length and guarantees reproducibility, unambiguous analysis and the possibility of comparing and transferring data between different laboratories. The plasticity of the method still supports the addition of extra molecular markers targeting specific purposes/populations. SNaPaer can be of great value to clinical laboratories by facilitating routine genotyping of P. aeruginosa.     

Diel timing of planulation and larval settlement in the coral Isopora cuneata (Scleractinia: Acroporidae)

The prevailing environmental conditions when reproductive products are released in the water column can have a profound influence on the biology and ecology of marine organisms. In reef-building corals, brooding species that release azooxanthellate larvae are expected to release their larvae before sunrise, similar to species releasing zooxanthellate larvae as established in previous studies. This study investigated the diel timing of release of asymbiotic larvae by Isopora cuneata in northwestern Philippines during 2 years through ex situ observations on gravid colonies collected from the reef. Planulation mainly occurred after sunset until midnight, with grand mean hour of release at 19:35 h (95% confidence limit: 18:44–21:02 h) in April 2010 and 19:41 h (18:10–20:59 h) in March 2011. This pattern of release timing is distinct from what has been previously reported for brooding scleractinian coral species with zooxanthellate larvae (i.e., release close to sunrise). The release coincides with the low tidal stand, which may provide opportunity for the prompt settlement of newly released, buoyant larvae to shallow reef areas where adult colonies are generally distributed. The larvae were able to settle with 20 ± 25% success within a day of release, though a distinct settlement peak at 3 days post-release (70 ± 25%). This study provides new information on the early life strategies of the reef-building coral Isopora cuneata. The unique pattern of larval release time and the settlement behavior may influence the population dynamics and success of the species through space and time.     

The Long Term Impact of Cataract Surgery on Quality of Life,Activities and Poverty: Results from a Six Year Longitudinal Study in Bangladesh and the Philippines

Background

Cataract surgery has been shown to improve quality of life and household economy in the short term. However, it is unclear whether these benefits are sustained over time. This study aims to assess the six year impact of cataract surgery on health related quality of life (HRQoL), daily activities and economic poverty in Bangladesh and The Philippines.

Methods and Findings

This was a longitudinal study. At baseline people aged ≥50 years with visual impairment due to cataract (‘cases’) and age-, sex-matched controls without visual impairment were interviewed about vision specific and generic HRQoL, daily activities and economic indicators (household per capita expenditure, assets and self-rated wealth). Cases were offered free or subsidised cataract surgery. Cases and controls were re-interviewed approximately one and six years later. At baseline across the two countries there were 455 cases and 443 controls. Fifty percent of cases attended for surgery. Response rates at six years were 47% for operated cases and 53% for controls. At baseline cases had poorer health and vision related QoL, were less likely to undertake productive activities, more likely to receive assistance with activities and were poorer compared to controls (p<0.05). One year after surgery there were significant increases in HRQoL, participation and time spent in productive activities and per capita expenditure and reduction in assistance with activities so that the operated cases were similar to controls. These increases were still evident after six years with the exception that time spent on productive activities decreased among both cases and controls.

Conclusion

Cataract causing visual loss is associated with reduced HRQoL and economic poverty among older adults in low-income countries. Cataract surgery improves the HRQoL of the individual and economy of the household. The findings of this study suggest these benefits are sustained in the long term.     

How Quickly do Fragments of Coral “Self‐Attach” after Transplantation?

Transplantation of coral fragments is seen as a potential method to rapidly restore coral cover to areas of degraded reef; however, considerable research is still needed to assess the effectiveness of coral transplantation as a viable reef restoration tool. Initially, during restoration efforts, coral transplants are attached artificially. Self‐attachment (i.e., growth of coral tissue onto the substrate) provides a more secure and lasting bond, thus knowledge about self‐attachment times for corals is of importance to reef restoration. While it is known that coral fragments may generate new tissue and bond to substrata within a few weeks of transplantation, surprisingly little is known about the speed of self‐attachment for most species. Two independent experiments were carried out to examine the self‐attachment times of 12 scleractinian and one non‐scleractinian coral species to a natural calcium carbonate substrate. The first experiment examined times to self‐attachment in 11 species of differing morphologies from seven families over approximately 7 months, whereas the second experiment examined three fast‐attaching Acropora species over approximately 1 month. In the first experiment, the branching species Acropora muricata had a significantly faster self‐attachment time compared to all other species, while Echinopora lamellosa had the slowest self‐attachment time. For the second experiment, A. muricata was significantly slower to self‐attach than Acropora hyacinthus (tabular) and Acropora digitifera (corymbose‐digitate). The results suggest that a combination of factors including growth rates, growth form and life history may determine how quickly fragments of coral species self‐attach after fragmentation and transplantation.     

Antibodies Generated against Conserved Antigens Expressed by Bacteria and Allergen-Bearing Fungi Suppress Airway Disease

There has been a sharp rise in allergic asthma and asthma-related deaths in the developed world, in contrast to many childhood illnesses that have been reduced or eliminated. The hygiene hypothesis proposes that excessively sanitary conditions early in life result in autoimmune and allergic phenomena because of a failure of the immune system to receive proper microbial stimulation during development. We demonstrate that Abs generated against conserved bacterial polysaccharides are reactive with and dampen the immune response against chitin and Aspergillus fumigatus. A reduction in Ag uptake, cell influx, cell activation, and cytokine production occurred in the presence of anti-polysaccharide Abs, resulting in a striking decrease in the severity of allergic airway disease in mice. Overall, our results suggest that Ag exposure-derived from environmental sources, self-antigens, or vaccination-during the neonatal period has dramatic effects on the adult Ab response and modifies the development of allergic airway disease.