International Laboratory Comparison of Influenza Microneutralization Assays for A(H1N1) pdm09, A(H3N2), and A(H5N1) Influenza Viruses by CONSISE

The microneutralization assay is commonly used to detect antibodies to influenza virus, and multiple protocols are used worldwide. These protocols differ in the incubation time of the assay as well as in the order of specific steps, and even within protocols there are often further adjustments in individual laboratories. The impact these protocol variations have on influenza serology data is unclear. Thus, a laboratory comparison of the 2-day enzyme-linked immunosorbent assay (ELISA) and 3-day hemagglutination (HA) microneutralization (MN) protocols, using A(H1N1)pdm09, A(H3N2), and A(H5N1) viruses, was performed by the CONSISE Laboratory Working Group. Individual laboratories performed both assay protocols, on multiple occasions, using different serum panels. Thirteen laboratories from around the world participated. Within each laboratory, serum sample titers for the different assay protocols were compared between assays to determine the sensitivity of each assay and were compared between replicates to assess the reproducibility of each protocol for each laboratory. There was good correlation of the results obtained using the two assay protocols in most laboratories, indicating that these assays may be interchangeable for detecting antibodies to the influenza A viruses included in this study. Importantly, participating laboratories have aligned their methodologies to the CONSISE consensus 2-day ELISA and 3-day HA MN assay protocols to enable better correlation of these assays in the future

Hazard Analysis of Critical Control Points Assessment as a Tool to Respond to Emerging Infectious Disease Outbreaks

Highly pathogenic avian influenza virus (HPAI) strain H5N1 has had direct and indirect economic impacts arising from direct mortality and control programmes in over 50 countries reporting poultry outbreaks. HPAI H5N1 is now reported as the most widespread and expensive zoonotic disease recorded and continues to pose a global health threat. The aim of this research was to assess the potential of utilising Hazard Analysis of Critical Control Points (HACCP) assessments in providing a framework for a rapid response to emerging infectious disease outbreaks. This novel approach applies a scientific process, widely used in food production systems, to assess risks related to a specific emerging health threat within a known zoonotic disease hotspot. We conducted a HACCP assessment for HPAI viruses within Vietnam’s domestic poultry trade and relate our findings to the existing literature. Our HACCP assessment identified poultry flock isolation, transportation, slaughter, preparation and consumption as critical control points for Vietnam’s domestic poultry trade. Introduction of the preventative measures highlighted through this HACCP evaluation would reduce the risks posed by HPAI viruses and pressure on the national economy. We conclude that this HACCP assessment provides compelling evidence for the future potential that HACCP analyses could play in initiating a rapid response to emerging infectious diseases

Studies Needed to Address Public Health Challenges of the 2009 H1N1 Influenza Pandemic: Insights from Modeling

In light of the 2009 influenza pandemic and potential future pandemics, Maria Van Kerkhove and colleagues anticipate six public health challenges and the data needed to support sound public health decision making.The authors acknowledge support from the Bill & Melinda Gates Foundation (MDVK, CF, NMF); Royal Society (CF); Medical Research Council (MDVK, CF, PJW, NMF); EU FP7 programme (NMF); UK Health Protection Agency (PJW); US National Institutes of Health Models of Infectious Disease Agent Study program through cooperative agreement 1U54GM088588 (ML); NIH Director's Pioneer Award, DP1-OD000490-01 (DS); EU FP7 grant EMPERIE 223498 (DS); the Wellcome Trust (DS); 3R01TW008246-01S1 from Fogerty International Center and RAPIDD program from Fogerty International Center with the Science & Technology Directorate, Department of Homeland Security (SR); and the Institut de Veille Sanitaire Sanitaire funded by the French Ministry of Health (J-CD). The funders played no role in the decision to submit the article or in its preparation

Evaluation of Exposure to Arsenic in Residential Soil

In response to concerns regarding arsenic in soil from a pesticide manufacturing plant, we conducted a biomonitoring study on children younger than 7 years of age, the age category of children most exposed to soil. Urine samples from 77 children (47% participation rate) were analyzed for total arsenic and arsenic species related to ingestion of inorganic arsenic. Older individuals also provided urine (n = 362) and toenail (n = 67) samples. Speciated urinary arsenic levels were similar between children (geometric mean, geometric SD, and range: 4.0, 2.2, and 0.89–17.7 μg/L, respectively) and older participants (3.8, 1.9, 0.91–19.9 μg/L) and consistent with unexposed populations. Toenail samples were < 1 mg/kg. Correlations between speciated urinary arsenic and arsenic in soil (r = 0.137, p = 0.39; n = 41) or house dust (r = 0.049, p = 0.73; n = 52) were not significant for children. Similarly, questionnaire responses indicating soil exposure were not associated with increased urinary arsenic levels. Relatively low soil arsenic exposure likely precluded quantification of arsenic exposure above background

How to think about informal proofs

This document is the Accepted Manuscript version of the following article: Brendan Larvor, ‘How to think about informal proofs’, Synthese, Vol. 187(2): 715-730, first published online 9 September 2011. The final publication is available at Springer via doi:10.1007/s11229-011-0007-5It is argued in this study that (i) progress in the philosophy of mathematical practice requires a general positive account of informal proof; (ii) the best candidate is to think of informal proofs as arguments that depend on their matter as well as their logical form; (iii) articulating the dependency of informal inferences on their content requires a redefinition of logic as the general study of inferential actions; (iv) it is a decisive advantage of this conception of logic that it accommodates the many mathematical proofs that include actions on objects other than propositions; (v) this conception of logic permits the articulation of project-sized tasks for the philosophy of mathematical practice, thereby supplying a partial characterisation of normal research in the fieldPeer reviewedFinal Accepted Versio

Identification of production challenges and benefits using value chain mapping of egg food systems in Nairobi, Kenya

Commercial layer and indigenous chicken farming in Nairobi and associated activities in the egg value chains are a source of livelihood for urban families. A value chain mapping framework was used to describe types of inputs and outputs from chicken farms, challenges faced by producers and their disease control strategies. Commercial layer farms were defined as farms keeping exotic breeds of chicken, whereas indigenous chicken farms kept different cross breeds of indigenous chicken. Four focus group discussions were held with producers of these chickens in peri-urban area: Dagoretti, and one informal settlement: Kibera. Qualitative data were collected on interactions between farmers, sources of farm inputs and buyers of poultry products, simple ranking of production challenges, farmers' perception on diseases affecting chicken and strategies for management of sick chicken and waste products. Value chain profiles were drawn showing sources of inputs and channels for distribution of chicken products. Production challenges and chicken disease management strategies were presented as qualitative summaries. Commercial layer farms in Dagoretti kept an average of 250 chickens (range 50–500); while flock sizes in Kibera were 12 chickens (range 5–20). Farms keeping indigenous chicken had an average of 23 chickens (range 8–40) in Dagoretti, and 10 chickens (range 5–16) in Kibera. Commercial layer farms in Dagoretti obtained chicks from distributors of commercial hatcheries, but farms in Kibera obtained chicks from hawkers who in turn sourced them from distributors of commercial hatcheries. Indigenous chicken farms from Dagoretti relied on natural hatching of fertilised eggs, but indigenous chicken farms in Kibera obtained chicks from their social connection with communities living in rural areas. Outlets for eggs from commercial layer farms included local shops, brokers, restaurants and hawkers, while eggs from indigenous chicken farms were sold to neighbours and restaurants. Sieved chicken manure from Dagoretti area was fed to dairy cattle; whereas non-sieved manure was used as fertilizer on crops. Production challenges included poor feed quality, lack of space for expansion, insecurity, occurrence of diseases and lack of sources of information on chicken management. In Kibera, sick and dead chickens were slaughtered and consumed by households; this practice was not reported in Dagoretti. The chicken layer systems contribute to food security of urban households, yet they have vulnerabilities and deficiencies with regard to disease management and food safety that need to be addressed with support on research and extension

Marburg hemorrhagic fever in Durba and Watsa, Democratic Republic of the Congo: clinical documentation, features of illness, and treatment

The objective of the present study was to describe day of onset and duration of symptoms of Marburg hemorrhagic fever (MHF), to summarize the treatments applied, and to assess the quality of clinical documentation. Surveillance and clinical records of 77 patients with MHF cases were reviewed. Initial symptoms included fever, headache, general pain, nausea, vomiting, and anorexia (median day of onset, day 1-2), followed by hemorrhagic manifestations (day 5-8+), and terminal symptoms included confusion, agitation, coma, anuria, and shock. Treatment in isolation wards was acceptable, but the quality of clinical documentation was unsatisfactory. Improved clinical documentation is necessary for a basic evaluation of supportive treatment

Estimating potential incidence of MERS-CoV associated with Hajj pilgrims to Saudi Arabia, 2014

Between March and June 2014 the Kingdom of Saudi Arabia (KSA) had a large outbreak of MERS-CoV, renewing fears of a major outbreak during the Hajj this October. Using KSA Ministry of Health data, the MERS-CoV Scenario and Modeling Working Group forecast incidence under three scenarios. In the expected incidence scenario, we estimate 6.2 (95% Prediction Interval [PI]: 1-17) pilgrims will develop MERS-CoV symptoms during the Hajj, and 4.0 (95% PI: 0-12) foreign pilgrims will be infected but return home before developing symptoms. In the most pessimistic scenario, 47.6 (95% PI: 32-66) cases will develop symptoms during the Hajj, and 29.0 (95% PI: 17-43) will be infected but return home asymptomatic. Large numbers of MERS-CoV cases are unlikely to occur during the 2014 Hajj even under pessimistic assumptions, but careful monitoring is still needed to detect possible mass infection events and minimize introductions into other countries

A simple approach to measure transmissibility and forecast incidence

Outbreaks of novel pathogens such as SARS, pandemic influenza and Ebola require substantial investments in reactive interventions, with consequent implementation plans sometimes revised on a weekly basis. Therefore, short-term forecasts of incidence are often of high priority. In light of the recent Ebola epidemic in West Africa, a forecasting exercise was convened by a network of infectious disease modellers. The challenge was to forecast unseen “future” simulated data for four different scenarios at five different time points. In a similar method to that used during the recent Ebola epidemic, we estimated current levels of transmissibility, over variable time-windows chosen in an ad hoc way. Current estimated transmissibility was then used to forecast near-future incidence. We performed well within the challenge and often produced accurate forecasts. A retrospective analysis showed that our subjective method for deciding on the window of time with which to estimate transmissibility often resulted in the optimal choice. However, when near-future trends deviated substantially from exponential patterns, the accuracy of our forecasts was reduced. This exercise highlights the urgent need for infectious disease modellers to develop more robust descriptions of processes – other than the widespread depletion of susceptible individuals – that produce non-exponential patterns of incidence