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Objective: To estimate injury mortality rates in a rural population in KwaZulu-Natal, South Africa and to identify socio-demographic risk factors associated with adult injury-related deaths.Methods: The study used population-based mortality data collected by a demographic surveillance system on all resident and non-resident members of 11,000 households. Deaths and person-years of observation (pyo) were aggregated for individuals between 01 January 2000 and 31 December 2007. Cause of death was determined by verbal autopsy, coded using ICD-10 and further categorised using global burden of disease categories. Socio-demographic risk factors associated with injuries were examined using regression analyses.Results: We analysed data on 133,483 individuals with 717,584.6 person-years of observation (pyo) and 11,467 deaths. Of deaths, 8.9% were because of injury-related causes; 11% occurred in children <15 years old. Homicide, road traffic injuries and suicide were the major causes. The estimated crude injury mortality rate was 142.4 (134.0, 151.4)/100,000 pyo; 116.9 (108.1, 126.5)/100,000 pyo among residents and 216.8 (196.5, 239.2)/100,000 pyo among non-residents. In multivariable analyses, the differences between residents and non-residents remained but were no longer significant for women. In men and women, full-time employment was significantly associated with lower mortality [adjusted rate ratios 0.6 (0.4, 0.9); 0.4 (0.2, 0.9)]; in men, higher asset ownership was independently associated with increased mortality [adjusted rate ratio 1.5 (1.1, 1.9)].Conclusions: Reducing the high levels of injury-related mortality in South Africa requires intersectoral primary prevention efforts that redress the root causes of violent and accidental deaths: social inequality, poverty and alcohol abuse. [ABSTRACT FROM AUTHOR]

D-mannose is widely used as non-antibiotic treatment for bacterial urinary tract infections. This application is based on a well-studied mechanism of binding to the type 1 bacterial pili and, therefore, blocking bacteria adhesion to the uroepithelial cells. To implement D-mannose into carrier systems, the mechanism of action of the sugar in the bladder environment is also relevant and requires investigation. Herein, two different MANNosylation strategies using mesoporous silica nanoparticles (MSNs) are described. The impact of different chemical linkers on bacterial adhesion and bladder cell response is studied via confocal microscopy imaging of the MSN interactions with the respective organisms. Cytotoxicity is assessed and the expression of Toll-like receptor 4 (TLR4) and caveolin-1 (CAV-1), in the presence or absence of simulated infection with bacterial lipopolysaccharide (LPS), is evaluated using the human urinary bladder cancer cell line T24. Further, localisation of the transcription factor NF-κB due to the MANNosylated materials is examined over time. The results show that MANNosylation modifies bacterial adhesion to the nanomaterials and significantly affects TLR4, caveolin-1, and NF-κB in bladder cells. These elements are essential components of the inflammatory cascade/pathogens response during urinary tract infections. These findings demonstrate that MANNosylation is a versatile tool to design hybrid nanocarriers for targeted biomedical applications., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Background: Women live on average five years longer than men, and the sex difference in longevity is typically lower in populations with high mortality. South Africa-a high mortality population with a large sex disparity-is an exception, but the causes of death that contribute to this difference are not well understood., Methods: Using data from a demographic surveillance system in rural KwaZulu-Natal (2000-2014), we estimate differences between male and female adult life expectancy by HIV status. The contribution of causes of death to these life expectancy differences are computed with demographic decomposition techniques. Cause of death information comes from verbal autopsy interviews that are interpreted with the InSilicoVA tool., Results: Adult women lived an average of 10.4 years (95% confidence Interval 9.0-11.6) longer than men. Sex differences in adult life expectancy were even larger when disaggregated by HIV status: 13.1 (95% confidence interval 10.7-15.3) and 11.2 (95% confidence interval 7.5-14.8) years among known HIV negatives and positives, respectively. Elevated male mortality from pulmonary tuberculosis (TB) and external injuries were responsible for 43% and 31% of the sex difference in life expectancy among the HIV negative population, and 81% and 16% of the difference among people living with HIV., Conclusions: The sex differences in adult life expectancy in rural KwaZulu-Natal are exceptionally large, atypical for an African population, and largely driven by high male mortality from pulmonary TB and injuries. This is the case for both HIV positive and HIV negative men and women, signalling a need to improve the engagement of men with health services, irrespective of their HIV status.

Background: Self-interviews, where the respondent rather than the interviewer enters answers to questions, have been proposed as a way to reduce social desirability bias associated with interviewer-led interviews. Computer-assisted self-interviews (CASI) are commonly proposed since the computer programme can guide respondents; however they require both language and computer literacy. We evaluated the feasibility and acceptability of using electronic methods to administer quantitative sexual behaviour questionnaires in the Somkhele demographic surveillance area (DSA) in rural KwaZulu-Natal, South Africa., Methods: We conducted a four-arm randomized trial of paper-and-pen-interview, computer-assisted personal-interview (CAPI), CASI and audio-CASI with an age-sex-urbanicity stratified sample of 504 adults resident in the DSA in 2015. We compared respondents' answers to their responses to the same questions in previous surveillance rounds. We also conducted 48 cognitive interviews, dual-coding responses using the Framework approach., Results: Three hundred forty (67%) individuals were interviewed and covariates and participation rates were balanced across arms. CASI and audio-CASI were significantly slower than interviewer-led interviews. Item non-response rates were higher in self-interview arms. In single-paper meta-analysis, self-interviewed individuals reported more socially undesirable sexual behaviours. Cognitive interviews found high acceptance of both self-interviews and the use of electronic methods, with some concerns that self-interview methods required more participant effort and literacy., Conclusions: Electronic data collection methods, including self-interview methods, proved feasible and acceptable for completing quantitative sexual behaviour questionnaires in a poor, rural South African setting. However, each method had both benefits and costs, and the choice of method should be based on context-specific criteria.

Background: Antiretroviral therapy (ART) substantially decreases morbidity and mortality in people living with HIV. In this study, we describe population-level trends in the adult life expectancy and trends in the residual burden of HIV mortality after the roll-out of a public sector ART programme in KwaZulu-Natal, South Africa, one of the populations with the most severe HIV epidemics in the world., Methods: Data come from the Africa Centre Demographic Information System (ACDIS), an observational community cohort study in the uMkhanyakude district in northern KwaZulu-Natal, South Africa. We used non-parametric survival analysis methods to estimate gains in the population-wide life expectancy at age 15 years since the introduction of ART, and the shortfall of the population-wide adult life expectancy compared with that of the HIV-negative population (ie, the life expectancy deficit). Life expectancy gains and deficits were further disaggregated by age and cause of death with demographic decomposition methods., Findings: Covering the calendar years 2001 through to 2014, we obtained information on 93 903 adults who jointly contribute 535 42 8 person-years of observation to the analyses and 9992 deaths. Since the roll-out of ART in 2004, adult life expectancy increased by 15·2 years for men (95% CI 12·4-17·8) and 17·2 years for women (14·5-20·2). Reductions in pulmonary tuberculosis and HIV-related mortality account for 79·7% of the total life expectancy gains in men (8·4 adult life-years), and 90·7% in women (12·8 adult life-years). For men, 9·5% is the result of a decline in external injuries. By 2014, the life expectancy deficit had decreased to 1·2 years for men (-2·9 to 5·8) and to 5·3 years for women (2·6-7·8). In 2011-14, pulmonary tuberculosis and HIV were responsible for 84·9% of the life expectancy deficit in men and 80·8% in women., Interpretation: The burden of HIV on adult mortality in this population is rapidly shrinking, but remains large for women, despite their better engagement with HIV-care services. Gains in adult life-years lived as well as the present life expectancy deficit are almost exclusively due to differences in mortality attributed to HIV and pulmonary tuberculosis., Funding: Wellcome Trust, the Bill & Melinda Gates Foundation, and the National Institutes of Health., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: In the current information age, the use of data has become essential for decision making in public health at the local, national, and global level. Despite a global commitment to the use and sharing of public health data, this can be challenging in reality. No systematic framework or global operational guidelines have been created for data sharing in public health. Barriers at different levels have limited data sharing but have only been anecdotally discussed or in the context of specific case studies. Incomplete systematic evidence on the scope and variety of these barriers has limited opportunities to maximize the value and use of public health data for science and policy., Methods: We conducted a systematic literature review of potential barriers to public health data sharing. Documents that described barriers to sharing of routinely collected public health data were eligible for inclusion and reviewed independently by a team of experts. We grouped identified barriers in a taxonomy for a focused international dialogue on solutions., Results: Twenty potential barriers were identified and classified in six categories: technical, motivational, economic, political, legal and ethical. The first three categories are deeply rooted in well-known challenges of health information systems for which structural solutions have yet to be found; the last three have solutions that lie in an international dialogue aimed at generating consensus on policies and instruments for data sharing., Conclusions: The simultaneous effect of multiple interacting barriers ranging from technical to intangible issues has greatly complicated advances in public health data sharing. A systematic framework of barriers to data sharing in public health will be essential to accelerate the use of valuable information for the global good.

The scale-up of antiretroviral therapy (ART) is expected to raise adult life expectancy in populations with high HIV prevalence. Using data from a population cohort of over 101,000 individuals in rural KwaZulu-Natal, South Africa, we measured changes in adult life expectancy for 2000-2011. In 2003, the year before ART became available in the public-sector health system, adult life expectancy was 49.2 years; by 2011, adult life expectancy had increased to 60.5 years--an 11.3-year gain. Based on standard monetary valuation of life, the survival benefits of ART far outweigh the costs of providing treatment in this community. These gains in adult life expectancy signify the social value of ART and have implications for the investment decisions of individuals, governments, and donors.

Background: Verbal autopsy (VA) is the only available approach for determining the cause of many deaths, where routine certification is not in place. Therefore, it is important to use standards and methods for VA that maximise efficiency, consistency and comparability. The World Health Organization (WHO) has led the development of the 2012 WHO VA instrument as a new standard, intended both as a research tool and for routine registration of deaths., Objective: A new public-domain probabilistic model for interpreting VA data, InterVA-4, is described, which builds on previous versions and is aligned with the 2012 WHO VA instrument., Design: The new model has been designed to use the VA input indicators defined in the 2012 WHO VA instrument and to deliver causes of death compatible with the International Classification of Diseases version 10 (ICD-10) categorised into 62 groups as defined in the 2012 WHO VA instrument. In addition, known shortcomings of previous InterVA models have been addressed in this revision, as well as integrating other work on maternal and perinatal deaths., Results: The InterVA-4 model is presented here to facilitate its widespread use and to enable further field evaluation to take place. Results from a demonstration dataset from Agincourt, South Africa, show continuity of interpretation between InterVA-3 and InterVA-4, as well as differences reflecting specific issues addressed in the design and development of InterVA-4., Conclusions: InterVA-4 is made freely available as a new standard model for interpreting VA data into causes of death. It can be used for determining cause of death both in research settings and for routine registration. Further validation opportunities will be explored. These developments in cause of death registration are likely to substantially increase the global coverage of cause-specific mortality data.

Background: The advent of the HIV pandemic and the more recent prevention and therapeutic interventions have resulted in extensive and rapid changes in cause-specific mortality rates in sub-Saharan Africa, and there is demand for timely and accurate cause-specific mortality data to steer public health responses and to evaluate the outcome of interventions. The objective of this study is to describe cause-specific mortality trends based on verbal autopsies conducted on all deaths in a rural population in KwaZulu-Natal, South Africa, over a 10-year period (2000-2009)., Methods: The study used population-based mortality data collected by a demographic surveillance system on all resident and nonresident members of 12,000 households. Cause of death was determined by verbal autopsy based on the standard INDEPTH/WHO verbal autopsy questionnaire. Cause of death was assigned by physician review and the Bayesian-based InterVA program., Results: There were 11,281 deaths over 784,274 person-years of observation of 125,658 individuals between Jan. 1, 2000 and Dec. 31, 2009. The cause-specific mortality fractions (CSMF) for the population as a whole were: HIV-related (including tuberculosis), 50%; other communicable diseases, 6%; noncommunicable lifestyle-related conditions, 15%; other noncommunicable diseases, 2%; maternal, perinatal, nutritional, and congenital causes, 1%; injury, 8%; indeterminate causes, 18%. Over the course of the 10 years of observation, the CSMF of HIV-related causes declined from a high of 56% in 2002 to a low of 39% in 2009 with the largest decline starting in 2004 following the introduction of an antiretroviral treatment program into the population. The all-cause age-standardized mortality rate (SMR) declined over the same period from a high of 174 (95% confidence interval [CI]: 165, 183) deaths per 10,000 person-years observed (PYO) in 2003 to a low of 116 (95% CI: 109, 123) in 2009. The decline in the SMR is predominantly due to a decline in the HIV-related SMR, which declined in the same period from 96 (95% CI: 89, 102) to 45 (95% CI: 40, 49) deaths per 10,000 PYO.There was substantial agreement (79% kappa = 0.68 (95% CI: 0.67, 0.69)) between physician coding and InterVA coding at the burden of disease group level., Conclusions: Verbal autopsy based methods enabled the timely measurement of changing trends in cause-specific mortality to provide policymakers with the much-needed information to allocate resources to appropriate health interventions.

Global gene expression analysis allows for the identification of transcripts that are differentially regulated during a disease state. Many groups, including our own, have identified hundreds of genes differentially regulated in response to prion infection. Eleven transcripts, upregulated in the brains of prion-infected animals, which were classified in the literature as stimulated by the cytokine interferon-gamma (IFN-γ), were identified. This is intriguing, as IFN-γ has recently been detected in the brains of prion-infected animals. Quantitation of several genes, categorized as IFN-γ inducible, by quantitative real-time polymerase chain reaction (qRT-PCR) confirms that these transcripts are upregulated. Future approaches for delineating the role of IFN-γ-induced transcripts and their function in prion infection are described.

Background: In developing countries, Health and Demographic Surveillance Systems (HDSSs) provide a framework for tracking demographic and health dynamics over time in a defined geographical area. Many HDSSs co-exist with facility-based data sources in the form of Health Management Information Systems (HMIS). Integrating both data sources through reliable record linkage could provide both numerator and denominator populations to estimate disease prevalence and incidence rates in the population and enable determination of accurate health service coverage., Objective: To measure the acceptability and performance of fingerprint biometrics to identify individuals in demographic surveillance populations and those attending health care facilities serving the surveillance populations., Methodology: Two HDSS sites used fingerprint biometrics for patient and/or surveillance population participant identification. The proportion of individuals for whom a fingerprint could be successfully enrolled were characterised in terms of age and sex., Results: Adult (18-65 years) fingerprint enrolment rates varied between 94.1% (95% CI 93.6-94.5) for facility-based fingerprint data collection at the Africa Centre site to 96.7% (95% CI 95.9-97.6) for population-based fingerprint data collection at the Agincourt site. Fingerprint enrolment rates in children under 1 year old (Africa Centre site) were only 55.1% (95% CI 52.7-57.4). By age 5, child fingerprint enrolment rates were comparable to those of adults., Conclusion: This work demonstrates the feasibility of fingerprint-based individual identification for population-based research in developing countries. Record linkage between demographic surveillance population databases and health care facility data based on biometric identification systems would allow for a more comprehensive evaluation of population health, including the ability to study health service utilisation from a population perspective, rather than the more restrictive health service perspective.

Objective: We present early life mortality rates in a largely rural population with high antenatal HIV prevalence, and investigate temporal and spatial associations with a prevention of mother-to-child transmission (PMTCT) programme, an HIV treatment programme, and maternal HIV., Design: A retrospective cohort analysis., Methods: All births from January 2000 to January 2007 to women in the Africa Centre demographic surveillance were included. Under-two child mortality rates (U2MR) computed as deaths per 1000 live-births per year; factors associated with mortality risk assessed with Weibull regression. Availability of PMTCT (single-dose nevirapine; sdNVP) and antiretroviral therapy (ART) in a programme included in multivariable analysis., Results: Eight hundred and forty-eight (6.2%) of 13 583 children under 2 years died. Deaths in under-twos declined by 49% between 2001 and 2006, from 86.3 to 44.1 deaths per thousand live-births. Mortality was independently associated with birth season (adjusted hazard ratio 1.16, 95% confidence interval 1.02-1.33), maternal education (1.21, 1.02-1.43), maternal HIV (4.34, 3.11-6.04) and ART availability (0.46, 0.33-0.65). Children born at home (unlikely to have received sdNVP) had a 35% higher risk of dying than children born in a facility where sdNVP was available (1.35, 1.04-1.74). For 2005 births the availability of PMTCT and ART in public health programmes would have explained 8 and 31% of the decline in U2MR since 2000., Conclusion: These findings confirm the importance of maternal survival, and highlight the importance of the PMTCT and especially maternal HIV treatment with direct benefits of improved survival of their young children.

Objective: To investigate trends in adult mortality in a population serviced by a public-sector antiretroviral therapy (ART) programme in rural South Africa using a demographic surveillance system., Methods: Verbal autopsies were conducted for all 7930 deaths observed between January 2000 and December 2006 in a demographic surveillance population of 74,500 in the Umkhanyakude district of northern KwaZulu-Natal province, South Africa. Age-standardized mortality rate ratios (SMRRs) were calculated for adults aged 25 to 49 years, the group most affected by HIV, for the 2 years before 2004 and the 3 subsequent years, during which ART had been available., Findings: Between 2002-2003 (the period before ART) and 2004-2006 (the period after ART), HIV-related age-standardized mortality declined significantly, from 22.52 to 17.58 per 1000 person-years in women 25-49 years of age (P < 0.001; SMRR: 0.780; 95% confidence interval, CI: 0.691-0.881), and from 26.46 to 18.68 per 1000 person-years in men 25-49 years of age (P < 0.001; SMRR: 0.706; 95% CI: 0.615-0.811). On sensitivity analysis the results were robust to the possible effect of misclassification of HIV-related deaths., Conclusion: Overall population mortality and HIV-related adult mortality declined significantly following ART roll-out in a community with a high prevalence of HIV infection. A clear public health message of the benefits of treatment, as revealed by these findings, should be part of a multi-faceted strategy to encourage people to find out their HIV serostatus and seek care.

Identification of genes expressed in response to prion infection may elucidate biomarkers for disease, identify factors involved in agent replication, mechanisms of neuropathology and therapeutic targets. Although several groups have sought to identify gene expression changes specific to prion disease, expression profiles rife with cell population changes have consistently been identified. Cuprizone, a neurotoxicant, qualitatively mimics the cell population changes observed in prion disease, resulting in both spongiform change and astrocytosis. The use of cuprizone-treated animals as an experimental control during comparative expression profiling allows for the identification of transcripts whose expression increases during prion disease and remains unchanged during cuprizone-triggered neuropathology. In this study, expression profiles from the brains of mice preclinically and clinically infected with Rocky Mountain Laboratory (RML) mouse-adapted scrapie agent and age-matched controls were profiled using Affymetrix gene arrays. In total, 164 genes were differentially regulated during prion infection. Eighty-three of these transcripts have been previously undescribed as differentially regulated during prion disease. A 0.4% cuprizone diet was utilized as a control for comparative expression profiling. Cuprizone treatment induced spongiosis and astrocyte proliferation as indicated by glial fibrillary acidic protein (Gfap) transcriptional activation and immunohistochemistry. Gene expression profiles from brain tissue obtained from cuprizone-treated mice identified 307 differentially regulated transcript changes. After comparative analysis, 17 transcripts unaffected by cuprizone treatment but increasing in expression from preclinical to clinical prion infection were identified. Here we describe the novel use of the prion disease mimetic, cuprizone, to control for cell population changes in the brain during prion infection.