The Case for Reactive Mass Oral Cholera Vaccinations

Cholera outbreaks have had catastrophic impact on societies for centuries. Despite more than half a century of advocacy for safe water, sanitation and hygiene, approximately 100,000 cholera cases and 5,000 deaths were reported in Zimbabwe between August 2008 and by July 2009. Safe and effective oral cholera vaccines have been licensed and used by affluent tourists for more than a decade to prevent cholera. We asked whether oral cholera vaccines could be used to protect high risk populations at a time of cholera. We calculated how many cholera cases could have been prevented if mass cholera vaccinations would have been implemented in reaction to past cholera outbreaks. We estimate that determined, well organized mass vaccination campaigns could have prevented 34,900 (40%) cholera cases and 1,695 deaths (40%) in Zimbabwe. In the sites with endemic cholera, Kolkata and Zanzibar, a significant number of cases could have been prevented but the impact would have been less dramatic. The barriers which currently prevent the implementation of mass vaccinations, including but not only the cost to purchase the vaccine, seem insurmountable. A concerted effort of donors and key decision makers will be needed to offer better protection to populations at risk

Post-orogenic shoshonitic magmas of the Yzerfontein pluton, South Africa: the 'smoking gun' of mantle melting and crustal growth during Cape granite genesis?

The post-orogenic Yzerfontein pluton, in the Saldania Belt of South Africa was constructed through numerous injections of shoshonitic magmas. Most magma compositions are adequately modelled as products of fractionation, but the monzogranites and syenogranites may have a separate origin. A separate high-Mg mafic series has a less radiogenic mantle source. Fine-grained magmatic enclaves in the intermediate shoshonitic rocks are autoliths. The pluton was emplaced between 533 ± 3 and 537 ± 3 Ma (LASF-ICP-MS U–Pb zircon), essentially synchronously with many granitic magmas of the Cape Granite Suite (CGS). Yzerfontein may represent a high-level expression of the mantle heat source that initiated partial melting of the local crust and produced the CGS granitic magmas, late in the Saldanian Orogeny. However, magma mixing is not evident at emplacement level and there are no magmatic kinships with the I-type granitic rocks of the CGS. The mantle wedge is inferred to have been enriched during subduction along the active continental margin. In the late- to post-orogenic phase, the enriched mantle partially melted to produce heterogeneous magma batches, exemplified by those that formed the Yzerfontein pluton, which was further hybridized through minor assimilation of crustal materials. Like Yzerfontein, the small volumes of mafic rocks associated with many batholiths, worldwide, are probably also lowvolume, high-level expressions of crustal growth through the emplacement of major amounts of mafic magma into the deep crust.IS

The public health significance of latrines discharging to groundwater used for drinking.

Faecal contamination of groundwater from pit latrines is widely perceived as a major threat to the safety of drinking water for several billion people in rural and peri-urban areas worldwide. On the floodplains of the Ganges-Brahmaputra-Meghna delta in Bangladesh, we constructed latrines and monitored piezometer nests monthly for two years. We detected faecal coliforms (FC) in 3.3-23.3% of samples at four sites. We differentiate a near-field, characterised by high concentrations and frequent, persistent and contiguous contamination in all directions, and a far-field characterised by rare, impersistent, discontinuous low-level detections in variable directions. Far-field FC concentrations at four sites exceeded 0 and 10 cfu/100 ml in 2.4-9.6% and 0.2-2.3% of sampling events respectively. The lesser contamination of in-situ groundwater compared to water at the point-of-collection from domestic wells, which itself is less contaminated than at the point-of-consumption, demonstrates the importance of recontamination in the well-pump system. We present a conceptual model comprising four sub-pathways: the latrine-aquifer interface (near-field); groundwater flowing from latrine to well (far-field); the well-pump system; and post-collection handling and storage. Applying a hypothetical dose-response model suggests that 1-2% of the diarrhoeal disease burden from drinking water is derived from the aquifer, 29% from the well-pump system, and 70% from post-collection handling. The important implications are (i) that leakage from pit latrines is a minor contributor to faecal contamination of drinking water in alluvial-deltaic terrains; (ii) fears of increased groundwater pollution should not constrain expanding latrine coverage, and (iii) that more attention should be given to reducing contamination around the well-head

Effect of a multicomponent intervention on antihypertensive medication intensification in rural South Asia: post-hoc analysis of a cluster RCT

BACKGROUND: Inadequate treatment of hypertension is a widespread problem, especially in South Asian countries where cardiovascular disease mortality rates are high. We aimed to explore the effect of a multicomponent intervention (MCI) on antihypertensive medication intensification among rural South Asians with hypertension. METHODS: A post-hoc analysis of a two-year cluster-randomized controlled trial including 2645 hypertensives aged≥ 40 years from 30 rural communities, 10 each, in Bangladesh, Pakistan, and Sri Lanka. Independent assessors collected information on participants' self-reports and physical inspection of medications. The main outcomes were the changes from baseline to 24 months in the following: 1) the therapeutic intensity score (TIS) for all (and class specific) antihypertensive medications; 2) the number of antihypertensive medications in all trial participants. RESULTS: At 24 months, the mean increase in the TIS score of all antihypertensive medications was 0.11 in the MCI group and 0.03 in the control group, with a between-group difference in the increase of 0.08 (95% CI (0.03, 0.12); P=0.002). In MCI compared to controls, a greater increase in the TIS of renin angiotensin-aldosterone system blockers (0.05; 95% CI (0.02, 0.07); P<0.001) and calcium channel blockers (0.03; 95% CI (0.00, 0.05);p=0.031) , and in the number of antihypertensive medications (0.11, 95% CI (0.02, 0.19);P=0.016) was observed. CONCLUSIONS: In rural communities in Bangladesh, Pakistan, and Sri Lanka, MCI led to a greater increase in antihypertensive medication intensification compared to the usual care among adults with hypertension. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02657746

Evaluation and use of surveillance system data toward the identification of high-risk areas for potential cholera vaccination: a case study from Niger.

In 2008, Africa accounted for 94% of the cholera cases reported worldwide. Although the World Health Organization currently recommends the oral cholera vaccine in endemic areas for high-risk populations, its use in Sub-Saharan Africa has been limited. Here, we provide the principal results of an evaluation of the cholera surveillance system in the region of Maradi in Niger and an analysis of its data towards identifying high-risk areas for cholera

Organizational aspects and implementation of data systems in large-scale epidemiological studies in less developed countries

BACKGROUND: In the conduct of epidemiological studies in less developed countries, while great emphasis is placed on study design, data collection, and analysis, often little attention is paid to data management. As a consequence, investigators working in these countries frequently face challenges in cleaning, analyzing and interpreting data. In most research settings, the data management team is formed with temporary and unskilled persons. A proper working environment and training or guidance in constructing a reliable database is rarely available. There is little information available that describes data management problems and solutions to those problems. Usually a line or two can be obtained in the methods section of research papers stating that the data are doubly-entered and that outliers and inconsistencies were removed from the data. Such information provides little assurance that the data are reliable. There are several issues in data management that if not properly practiced may create an unreliable database, and outcomes of this database will be spurious. RESULTS: We have outlined the data management practices for epidemiological studies that we have modeled for our research sites in seven Asian countries and one African country. CONCLUSION: Information from this model data management structure may help others construct reliable databases for large-scale epidemiological studies in less developed countries

A Bayesian approach for estimating typhoid fever incidence from large-scale facility-based passive surveillance data

Decisions about typhoid fever prevention and control are based on estimates of typhoid incidence and their uncertainty. Lack of specific clinical diagnostic criteria, poorly sensitive diagnostic tests, and scarcity of accurate and complete datasets contribute to difficulties in calculating age-specific population-level typhoid incidence. Using data from the Strategic Typhoid Alliance across Africa and Asia program, we integrated demographic censuses, healthcare utilization surveys, facility-based surveillance, and serological surveillance from Malawi, Nepal, and Bangladesh to account for under-detection of cases. We developed a Bayesian approach that adjusts the count of reported blood-culture-positive cases for blood culture detection, blood culture collection, and healthcare seeking—and how these factors vary by age—while combining information from prior published studies. We validated the model using simulated data. The ratio of observed to adjusted incidence rates was 7.7 (95% credible interval [CrI]: 6.0-12.4) in Malawi, 14.4 (95% CrI: 9.3-24.9) in Nepal, and 7.0 (95% CrI: 5.6-9.2) in Bangladesh. The probability of blood culture collection led to the largest adjustment in Malawi, while the probability of seeking healthcare contributed the most in Nepal and Bangladesh; adjustment factors varied by age. Adjusted incidence rates were within or below the seroincidence rate limits of typhoid infection. Estimates of blood-culture-confirmed typhoid fever without these adjustments results in considerable underestimation of the true incidence of typhoid fever. Our approach allows each phase of the reporting process to be synthesized to estimate the adjusted incidence of typhoid fever while correctly characterizing uncertainty, which can inform decision-making for typhoid prevention and control

Effectiveness and economic analysis of the whole cell/recombinant B subunit (WC/rbs) inactivated oral cholera vaccine in the prevention of traveller's diarrhoea

<p>Abstract</p> <p>Background</p> <p>Nowadays there is a debate about the indication of the oral whole-cell/recombinant B-subunit cholera vaccine (WC/rBS) in traveller's diarrhoea. However, a cost-benefit analysis based on real data has not been published.</p> <p>Methods</p> <p>A cost-effectiveness and cost-benefit study of the oral cholera vaccine (WC/rBS), Dukoral^®for the prevention of traveller's diarrhoea (TD) was performed in subjects travelling to cholera risk areas. The effectiveness of WC/rBS vaccine in the prevention of TD was analyzed in 362 travellers attending two International Vaccination Centres in Spain between May and September 2005.</p> <p>Results</p> <p>The overall vaccine efficacy against TD was 42,6%. Direct healthcare-related costs as well as indirect costs (lost vacation days) subsequent to the disease were considered. Preventive vaccination against TD resulted in a mean saving of 79.26 € per traveller.</p> <p>Conclusion</p> <p>According to the cost-benefit analysis performed, the recommendation for WC/rBS vaccination in subjects travelling to zones at risk of TD is beneficial for the traveller, regardless of trip duration and visited continent.</p

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network

Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Methods and Findings: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. Conclusion: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects

The H-band Emitting Region of the Luminous Blue Variable P Cygni: Spectrophotometry and Interferometry of the Wind

This is the final version of the article. Available from American Astronomical Society / IOP Publishing via the DOI in this record.We present the first high angular resolution observations in the near-infrared H band (1.6 μm) of the luminous blue variable star P Cygni. We obtained six-telescope interferometric observations with the CHARA Array and the MIRC beam combiner. These show that the spatial flux distribution is larger than expected for the stellar photosphere. A two-component model for the star (uniform disk) plus a halo (two-dimensional Gaussian) yields an excellent fit of the observations, and we suggest that the halo corresponds to flux emitted from the base of the stellar wind. This wind component contributes about 45% of the H-band flux and has an angular FWHM = 0.96 mas, compared to the predicted stellar diameter of 0.41 mas. We show several images reconstructed from the interferometric visibilities and closure phases, and they indicate a generally spherical geometry for the wind. We also obtained near-infrared spectrophotometry of P Cygni from which we derive the flux excess compared to a purely photospheric spectral energy distribution. The H-band flux excess matches that from the wind flux fraction derived from the two-component fits to the interferometry. We find evidence of significant near-infrared flux variability over the period from 2006 to 2010 that appears similar to the variations in the Hα emission flux from the wind.We acknowledge with thanks the variable star observations from the AAVSO International Database contributed by observers worldwide and used in this research. Support for Ritter Astrophysical Research Center during the time of the observations was provided by the National Science Foundation Program for Research and Education with Small Telescopes (NSF-PREST) under grant AST-0440784 (N.D.M.). This work was also supported by the National Science Foundation under grants AST-0606861 and AST-1009080 (D.R.G.). N.D.R. gratefully acknowledges his current CRAQ postdoctoral fellowship. We are grateful for the insightful comments of A. F. J. Moffat that improved portions of the paper, discussions with Paco Najarro and Luc Dessart about spectroscopic modeling of P Cygni, and support of the MIRC 6 telescope beam combiner by Ettore Pedretti. Institutional support has been provided by the GSU College of Arts and Sciences and by the Research Program Enhancement fund of the Board of Regents of the University System of Georgia, administered through the GSU Office of the Vice President for Research. Operational funding for the CHARA Array is provided by the GSU College of Arts and Sciences, by the National Science Foundation through grants AST-0606958 and AST-0908253, by the W. M. Keck Foundation, and by the NASA Exoplanet Science Institute. We thank the Mount Wilson Institute for providing infrastructure support at Mount Wilson Observatory. The CHARA Array, operated by Georgia State University, was built with funding provided by the National Science Foundation, Georgia State University, the W. M. Keck Foundation, and the David and Lucile Packard Foundation. This research was conducted in part using the Mimir instrument, jointly developed at Boston University and Lowell Observatory and supported by NASA, NSF, and the W. M. Keck Foundation. J.D.M. acknowledges University of Michigan and NSF AST-0707927 for support of MIRC construction and observations. D.P.C. acknowledges support under NSF AST-0907790 to Boston University. We gratefully acknowledge all of this support. This research has made use of the SIMBAD database operated at CDS, Strasbourg, France