The impact of prior information on estimates of disease transmissibility using Bayesian tools

The basic reproductive number (R₀) and the distribution of the serial interval (SI) are often used to quantify transmission during an infectious disease outbreak. In this paper, we present estimates of R₀ and SI from the 2003 SARS outbreak in Hong Kong and Singapore, and the 2009 pandemic influenza A(H1N1) outbreak in South Africa using methods that expand upon an existing Bayesian framework. This expanded framework allows for the incorporation of additional information, such as contact tracing or household data, through prior distributions. The results for the R₀ and the SI from the influenza outbreak in South Africa were similar regardless of the prior information (R0 = 1.36-1.46, μ = 2.0-2.7, μ = mean of the SI). The estimates of R₀ and μ for the SARS outbreak ranged from 2.0-4.4 and 7.4-11.3, respectively, and were shown to vary depending on the use of contact tracing data. The impact of the contact tracing data was likely due to the small number of SARS cases relative to the size of the contact tracing sample

Quantifying Temporal Variability in Stream Habitat Data: Implications for Restoration and Monitoring

Quantifying natural and anthropogenic-induced levels of temporal variability is essential for robust trend analyses and for evaluating the effectiveness of restoration activities or changed management actions. Here, we used data collected as part of the Pacfish/Infish Biological Effectiveness Monitoring Project to evaluate the extent of temporal variability in instream habitat collected at the reach scale. We integrated habitat data collected yearly (2001-2009) at 50 sites experiencing a range of management activities into our analyses to better understand the consistency of temporal variability in watersheds with inherently different landscape characteristics and disturbance regimes. We initially decomposed variance estimates to remove site-to-site variability, sampling error, and year effects and use the remaining variance as a measure of site-specific temporal variability. We then relate this temporal variability to landscape, management, and climate attributes at multiple scales to better understand which characteristics result in more or less variability in habitat attributes at specific sites. Our results suggest temporal variability differs significantly across individual sites and attributes within sites, indicating our ability to detect significant changes as a result of management changes and/or restoration efforts are context dependent. The spatial scale of landscape attributes, e.g., stream buffer vs. catchment, related to temporal variability also varied across individual attributes. Our efforts highlight the importance of considering site specific measures of temporal variability as they relate to specific restoration and management goals

Outbreak of Rift Valley fever affecting veterinarians and farmers in South Africa, 2008

Background. During 2008, Rift Valley fever (RVF) virus re-emerged in South Africa as focal outbreaks in several provinces. Aims. To investigate an outbreak affecting cattle farmers and farm workers, and the staff and students of a veterinary school, assess the prevalence of infection during the outbreak, document the clinical presentation of cases, and identify potential risk factors. Methods. We conducted a cross-sectional serological survey of exposed veterinarians and farmers, who were examined to determine the presence of current or recent illness. Blood specimens were collected for virus isolation, nucleic acid detection and serology. A subset was interviewed using a standardised questionnaire to obtain data on recent exposures and risk factors for infection. Results. Of 53 participants potentially exposed to infected domestic ruminants, 15% had evidence of recent infection and 4% evidence of past exposure to the RVF virus. The prevalence of acute infection was 21% in veterinarians compared with 9% in farmers and farm workers. After a mean incubation period of 4.3 days, the most frequent symptoms experienced included myalgia (100%), headache (88%) and malaise (75%). No asymptomatic cases were identified. Transmission by direct contact with infected animals was the major risk factor in these professional groups. Performing animal autopsies was significantly associated with acute infection (risk ratio 16.3, 95% confidence interval 2.3 - 114.2). Conclusions. Increased risks associated with veterinary practices highlight a need for the use of personal protective equipment, and identify veterinarians as a primary target group for future vaccination. Results. Of 53 participants potentially exposed to infected domestic ruminants, 15% had evidence of recent infection whilst 4% of past exposure to the RVF virus. The prevalence of acute infection was higher in veterinarians (21%) in comparison to farmers and farm workers (9%). After a mean incubation period of 4.3 days, the most frequent symptoms experienced included myalgia (100%), headache (88%) and malaise (75%). No asymptomatic cases were identified. Transmission by direct contact with infected animals was identified as the major risk factor in these professional groups. Performing animal autopsies was significantly associated with acute infection (risk ratio 16.3, 95% CI 2.3-114.2). Conclusions. Increased risks associated with veterinary practices highlight a need for the use of personal protective equipment, and identify veterinarians as a primary target group for future vaccination

Serum levels of inflammatory cytokines in Rift Valley fever patients are indicative of severe disease

BACKGROUND : Rift Valley fever (RVF) is a mosquito-borne viral zoonosis affecting domestic and wild ruminants, camels and humans. Outbreaks of RVF are characterized by a sudden onset of abortions and high mortality amongst domestic ruminants. Humans develop disease ranging from a mild flu-like illness to more severe complications including hemorrhagic syndrome, ocular and neurological lesions and death. During the RVF outbreak in South Africa in 2010/11, a total of 278 human cases were laboratory confirmed, including 25 deaths. The role of the host inflammatory response to RVF pathogenesis is not completely understood. METHODS : Virus load in serum from human fatal and non-fatal cases was determined by standard tissue culture infective dose 50 (TCID50) titration on Vero cells. Patient serum concentration of chemokines and cytokines involved in inflammatory responses (IL-8, RANTES, CXCL9, MCP-1, IP-10, IL-1β, IL-6, IL-10, TNF and IL-12p70) was determined using cytometric bead assays and flow cytometry. RESULTS : Fatal cases had a 1-log10 higher TCID50/ml serum concentration of RVF virus (RVFV) than survivors (p < 0.05). There were no significant sequence differences between isolates recovered from fatal and non-fatal cases. Chemokines and pro- and anti-inflammatory cytokines were detected at significantly increased (IL-8, CXCL9, MCP-1, IP-10, IL-10) or decreased (RANTES) levels when comparing fatal cases to infected survivors and uninfected controls, or when comparing combined infected patients to uninfected controls. CONCLUSIONS : The results suggest that regulation of the host inflammatory responses plays an important role in the outcome of RVFV infection in humans. Dysregulation of the inflammatory response contributes to a fatal outcome. The cytokines and chemokines identified in this study that correlate with fatal outcomes warrant further investigation as markers for disease severity.The Poliomyelitis Research Foundation (PRF), grant number 12/10. PJvV is further supported by a grant from the Incentive Funding for Rated Researchers program of the National Research Foundation (NRF), South Africa. This work is based on the research supported in part by the National Research Foundation of South Africa (Grant specific unique reference number UID 85544).http://www.virologyj.comam201

Typhoid Fever and Invasive Nontyphoid Salmonellosis, Malawi and South Africa

To determine the prevalence of invasive nontyphoid salmonellosis and typhoid fever in Malawi and South Africa, we compared case frequency and patient age distribution. Invasive nontyphoid salmonellosis showed a clear bimodal age distribution; the infection developed in women at a younger age than in men. Case frequency for typhoid fever was lower than for salmonellosis

School closures during the 2009 influenza pandemic: national and local experiences

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Measles outbreak in South Africa: epidemiology of laboratory-confirmed measles cases and assessment of intervention, 2009-2011

BACKGROUND: Since 1995, measles vaccination at nine and 18 months has been routine in South Africa; however, coverage seldom reached .95%. We describe the epidemiology of laboratory-confirmed measles case-patients and assess the impact of the nationwide mass vaccination campaign during the 2009 to 2011 measles outbreak in South Africa. METHODS: Serum specimens collected from patients with suspected-measles were tested for measles-specific IgM antibodies using an enzyme-linked immunosorbent assay and genotypes of a subset were determined. To estimate the impact of the nationwide mass vaccination campaign, we compared incidence in the seven months pre- (1 September 2009–11 April 2010) and seven months post-vaccination campaign (24 May 2010–31 December 2010) periods in seven provinces of South Africa. RESULTS: A total of 18,431 laboratory-confirmed measles case-patients were reported from all nine provinces of South Africa (cumulative incidence 37 per 100,000 population). The highest cumulative incidence per 100,000 population was in children aged ,1 year (603), distributed as follows: ,6 months (302/100,000), 6 to 8 months (1083/100,000) and 9 to 11 months (724/100,000). Forty eight percent of case-patients were $5 years (cumulative incidence 54/100,000). Cumulative incidence decreased with increasing age to 2/100,000 in persons$40 years. A single strain of measles virus (genotype B3) circulated throughout the outbreak. Prior to the vaccination campaign, cumulative incidence in the targeted vs. non-targeted age group was 5.9-fold higher, decreasing to 1.7 fold following the campaign (P,0.001) and an estimated 1,380 laboratoryconfirmed measles case-patients were prevented. CONCLUSION: We observed a reduction in measles incidence following the nationwide mass vaccination campaign even though it was conducted approximately one year after the outbreak started. A booster dose at school entry may be of value given the high incidence in persons .5 years.Our acknowledgements go to the Department of Health South Africa, National, provincial and districts, the South African Field Epidemiology and Laboratory Training Programme (SAFELTP), for ongoing support in surveillance and outbreak activities; Division of Epidemiology (Tsakani Nkuna, Kelebogile Lebogang Motsepe) and Virology (Londiwe Mahlaba, Mduduzi Buthelezi, Nomfundo Radebe, Muzi Hlanzi, Wayne Howard) at the NICD-NHLS for data management and laboratory testing support respectively and Private Laboratories for their support and referring specimens to the NICD.www.plosone.orgam201

An Ancient Duplication of Exon 5 in the Snap25 Gene Is Required for Complex Neuronal Development/Function

Alternative splicing is an evolutionary innovation to create functionally diverse proteins from a limited number of genes. SNAP-25 plays a central role in neuroexocytosis by bridging synaptic vesicles to the plasma membrane during regulated exocytosis. The SNAP-25 polypeptide is encoded by a single copy gene, but in higher vertebrates a duplication of exon 5 has resulted in two mutually exclusive splice variants, SNAP-25a and SNAP-25b. To address a potential physiological difference between the two SNAP-25 proteins, we generated gene targeted SNAP-25b deficient mouse mutants by replacing the SNAP-25b specific exon with a second SNAP-25a equivalent. Elimination of SNAP-25b expression resulted in developmental defects, spontaneous seizures, and impaired short-term synaptic plasticity. In adult mutants, morphological changes in hippocampus and drastically altered neuropeptide expression were accompanied by severe impairment of spatial learning. We conclude that the ancient exon duplication in the Snap25 gene provides additional SNAP-25-function required for complex neuronal processes in higher eukaryotes

Identifying educator behaviours for high quality verbal feedback in health professions education: literature review and expert refinement

Background Health professions education is characterised by work-based learning and relies on effective verbal feedback. However the literature reports problems in feedback practice, including lack of both learner engagement and explicit strategies for improving performance. It is not clear what constitutes high quality, learner-centred feedback or how educators can promote it. We hoped to enhance feedback in clinical practice by distinguishing the elements of an educator’s role in feedback considered to influence learner outcomes, then develop descriptions of observable educator behaviours that exemplify them. Methods An extensive literature review was conducted to identify i) information substantiating specific components of an educator’s role in feedback asserted to have an important influence on learner outcomes and ii) verbal feedback instruments in health professions education, that may describe important educator activities in effective feedback. This information was used to construct a list of elements thought to be important in effective feedback. Based on these elements, descriptions of observable educator behaviours that represent effective feedback were developed and refined during three rounds of a Delphi process and a face-to-face meeting with experts across the health professions and education. Results The review identified more than 170 relevant articles (involving health professions, education, psychology and business literature) and ten verbal feedback instruments in health professions education (plus modified versions). Eighteen distinct elements of an educator’s role in effective feedback were delineated. Twenty five descriptions of educator behaviours that align with the elements were ratified by the expert panel. Conclusions This research clarifies the distinct elements of an educator’s role in feedback considered to enhance learner outcomes. The corresponding set of observable educator behaviours aim to describe how an educator could engage, motivate and enable a learner to improve. This creates the foundation for developing a method to systematically evaluate the impact of verbal feedback on learner performance