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bioRxiv2018

MicroCOSM: a model of social and structural drivers of HIV and interventions to reduce HIV incidence in high-risk populations in South Africa

Executive summaryO_ST_ABSBackground and objectivesC_ST_ABSSouth Africa has one of the highest HIV incidence rates in the world. Although much research has focused on developing biomedical strategies to reduce HIV incidence, there has been less investment in prevention strategies that address the social drivers of HIV spread. Understanding the social determinants of HIV is closely related to understanding high-risk populations ( key populations), since many of the factors that place these key populations at high HIV risk are social and behavioural rather than biological.\n\nMathematical models have an important role to play in evaluating the potential impact of new HIV prevention and treatment strategies. However, most of the mathematical modelling studies that have been published to date have evaluated biomedical HIV prevention strategies, and relatively few models have been developed to understand the role of social determinants or interventions that address these social drivers. In addition, many of the mathematical models that have been developed are relatively simple deterministic models, which are not well suited to simulating the complex causal pathways that link many of the social drivers to HIV incidence. The frequency-dependent assumption implicit in most deterministic models also leads to under-estimation of the contribution of high-risk groups to the incidence of HIV.\n\nAgent-based models (ABMs) overcome many of the limitations of deterministic models, although at the expense of greater computational burden. This study presents an ABM of HIV in South Africa, developed to characterize the key social drivers of HIV in South Africa and the groups that are at the highest risk of HIV. The objective of this report is to provide a technical description of the model and to explain how the model has been calibrated to South African data sources; future publications will assess the drivers of HIV transmission in South Africa in more detail.\n\nMethodsThe model is an extension of a previously-published ABM of HIV and other sexually transmitted infections (STIs) in South Africa. This model simulates a representative sample of the South African population, starting from 1985, with an initial sample size of 20 000. The population changes in size as a result of births and deaths. Each individual is assigned a date of birth, sex and race (demographic characteristics). This in turn affects the assignment of socio-economic variables. Each individual is assigned a level of educational attainment, which is dynamically updated as youth progress through school and tertiary education, with rates of progression and drop-out depending on the individuals demographic characteristics. Each individual is also assigned to an urban or rural location, with rates of movement between urban and rural areas depending on demographic characteristics and educational attainment.\n\nThe model assigns to each individual a number of healthcare access variables that determine their HIV and pregnancy risk. These include their condom preference (a measure of the extent to which they wish to use condoms and are able to access condoms), use of hormonal contraception and sterilization, use of pre-exposure prophylaxis (PrEP), male circumcision, HIV testing history and uptake of antiretroviral treatment (ART). Access to these healthcare services changes over time, and is also assumed to depend on demographic and socioeconomic variables, as well as on the individuals health status.\n\nSexual behaviour is simulated by assigning to each individual an indicator of their propensity for concurrent partnerships ( high risk individuals are defined as individuals who have a propensity for concurrent partnerships or commercial sex). Each individual is also assigned a sexual preference, which can change over their life course. Three types of relationship are modelled: sex worker-client contacts, short-term (non-marital) relationships and long-term (marital or cohabiting) relationships. Individuals are assumed to enter into short-term relationships at rates that depend on their risk group and demographic characteristics. Each time a new short-term partner is acquired, the individual is linked to another individual in the population, with the probability of linkage depending on the individuals sexual preference and preference for individuals of the relevant age, risk group, race, location and educational attainment. Individuals marry their short-term partners at rates that depend on their demographic characteristics. Frequencies of sex are assumed to depend on demographic characteristics and relationship type, and migrant couples are assumed to have reduced coital frequency. Probabilities of condom use also depend on demographic characteristics and relationship type, and are assumed to be strongly associated with levels of educational attainment.\n\nWomens risk of falling pregnant is assumed to depend on their sexual behaviour, natural fertility level, contraceptive usage and breastfeeding status. Adoption and discontinuation of hormonal contraception is assumed to depend on demographic characteristics, sexual behaviour and past pregnancy and contraceptive experience. Girls who fall pregnant while in school are assumed to be less likely to complete their schooling than those who do not fall pregnant.\n\nProbabilities of HIV transmission per act of sex are assumed to depend on several biological factors, including the viral load of the HIV-positive partner, whether the HIV-positive partner is on ART, the presence of other STIs, the type of contraceptive used, the age and sex of the susceptible partner, male circumcision, the type of relationship, and the use of new HIV prevention methods such as PrEP. If an individual acquires HIV, they are assigned a CD4 count and viral load, both of which change dynamically over the course of HIV infection. The HIV mortality risk is determined by the individuals CD4 count. HIV-positive individuals are diagnosed at rates that depend on their demographic characteristics and CD4 count, and if they disclose their HIV status to their sexual partners after diagnosis, this is assumed to lead to increased rates of condom use. Assumptions about HIV transmission probabilities have been set in such a way that the model matches the observed trends in HIV prevalence, by age and sex, in national South African antenatal and household surveys.\n\nThe model also simulates male incarceration. Rates of incarceration are assumed to depend on mens demographic characteristics and educational attainment, and are also assumed to be higher in men who have previously been incarcerated.\n\nResults and conclusionsThe model matches reasonably closely the observed levels of HIV prevalence in South Africa by age and sex, as well as the observed changes in HIV prevalence over time. The model also matches observed patterns of HIV prevalence by educational attainment, by urban-rural location and by history of recent migration. Estimates of HIV prevalence in key populations (sex workers, MSM and prisoners) are roughly consistent with surveys. The model has also been calibrated to match total numbers of HIV tests and male circumcision operations performed in South Africa. The model estimates of levels of HIV diagnosis and ART coverage are consistent with the Thembisa model, an HIV model that has been calibrated to South African HIV testing and ART data.\n\nAlthough many of the phenomena simulated in the MicroCOSM model have been simulated in previously-published HIV models, MicroCOSM is the first model that systematically describes all of these phenomena in a fully integrated model. This makes it possible to use the model to describe complex interactions between socio-economic and behavioural factors, and their influence on disease and health-seeking behaviour. It also provides a framework for understanding socio-economic and racial inequality in health outcomes in South Africa, and for assessing the potential impact of strategies to reduce these inequalities.

epidemiology↗

bioRxiv2018

Inter-annual variation in seasonal dengue epidemics driven bymultiple interacting factors in Guangzhou, China

Vector-borne diseases display wide inter-annual variation in seasonal epidemic size due to their complex dependence on temporally variable environmental conditions and other factors. In 2014, Guangzhou, China experienced its worst dengue epidemic on record, with incidence exceeding the historical average by two orders of magnitude. To disentangle contributions from multiple factors to inter-annual variation in epidemic size, we fitted a semi-mechanistic model to time series data from 2005-2015 and performed a series of factorial simulation experiments in which seasonal epidemics were simulated under all combinations of year-specific patterns of four time-varying factors: imported cases, mosquito density, temperature, and residual variation in local conditions not explicitly represented in the model. Our results indicate that while epidemics in most years were limited by unfavorable conditions with respect to one or more factors, the epidemic in 2014 was made possible by the combination of favorable conditions for all factors considered in our analysis.

epidemiology↗

bioRxiv2018

The impact of a governmental cash transfer programme on tuberculosis cure rate in Brazil: A quasi-experimental approach

BackgroundSocial vulnerability is strongly associated with tuberculosis (TB) indicators like cure rate. By addressing key social determinants, social protection policies such as Brazils Bolsa Familia Programme (BFP), a governmental conditional cash transfer, may play a role in TB control. Evidence is consolidating around a positive effect of social protection on TB outcomes, however methodological limitations prevent strong conclusions. This paper uses a quasi-experimental approach to more rigorously evaluate the effect of BFP on TB cure rate.\n\nMethods & FindingsThe data source was Brazils TB notification system (SINAN), linked to the national registry of those in poverty (CadUnico) and the BFP payroll. Propensity scores (PSs) were estimated from a complete-case logistic regression using covariates from this linked dataset, informed by a directed acyclic graph. Control patients were matched to exposed patients on the PS and the average effect of treatment on the treated (ATT) was estimated as the difference in TB cure rate between matched groups (n = 2167). The ATT was estimated as 10{middle dot}58 (95% CIs: 4{middle dot}39, 16{middle dot}77). This suggests that 10{middle dot}58% of the TB patients receiving BFP who were cured would not have been cured had they not received BFP. The direction of this effect was robust to sensitivity analyses performed and the PS matching broadly improved balance, although missing data limited the sample size.\n\nConclusionsThis work is the first quasi-experimental evaluation of social protection in wide-scale practice on TB outcomes. It demonstrates a positive effect of conditional cash transfers on TB cure rate consistent with existing work, suggesting changes to policy and future research on increasing access to social protection for TB patients who remain uncovered by the programme.

epidemiology↗

bioRxiv2018

Short-term effectiveness of HIV care coordination among persons with recent HIV diagnosis or history of poor HIV outcomes

The New York City HIV Care Coordination Program (CCP) combines multiple evidence-based strategies to support persons living with HIV (PLWH) at risk for, or with a recent history of, poor HIV outcomes. We assessed the comparative effectiveness of the CCP by merging programmatic data on CCP clients with population-based surveillance data on all New York City PLWH. A non-CCP comparison group of similar PLWH who met CCP eligibility criteria was identified using surveillance data. The CCP and non-CCP groups were matched on propensity for CCP enrollment within four baseline treatment status groups (newly diagnosed or previously diagnosed and either consistently unsuppressed, inconsistently suppressed or consistently suppressed). We compared CCP to non-CCP proportions with viral load suppression at 12-month follow-up. Among the 13,624 persons included, 15{middle dot}3% were newly diagnosed; among the 84{middle dot}7% previously diagnosed, 14{middle dot}2% were consistently suppressed, 28{middle dot}9% were inconsistently suppressed, and 41 {middle dot}6% were consistently unsuppressed in the year prior to baseline. At 12-month follow-up, 59{middle dot}9% of CCP and 53{middle dot}9% of non-CCP participants had viral load suppression (Relative Risk=1.11, 95%CI:1.08-1.14). Among those newly diagnosed and those consistently unsuppressed at baseline, the relative risk of viral load suppression in the CCP versus non-CCP participants was 1.15 (95%CI:1.09-1.23) and 1.32 (95%CI:1.23-1.42), respectively. CCP exposure shows benefits over no CCP exposure for persons newly diagnosed or consistently unsuppressed, but not for persons suppressed in the year prior to baseline. We recommend more targeted case finding for CCP enrollment and increased attention to viral load suppression maintenance.

epidemiology↗

bioRxiv2018

Basidiobolus haptosporus-like fungus as a causal agent of gastrointestinal basidiobolomycosis and its link to the common house gecko (Hemidactylus frenatus) as a potential risk factor

Basidiobolus spp. are a significant causal agent of infections in man and animals including gastrointestinal basidiobolomycosis (GIB). Little information is available on how these infections are acquired or transmitted, apart from the postulation that environmental sources are implicated. This study aimed to identify Basidiobolus spp. from GIB patients and from the house gecko as a possible source of infection in Aseer, Saudi Arabia. Basidiobolus spp. were isolated from patient specimens (colonic mass biopsy) and from house gecko (gut contents) from Muhayil Aseer areas, in southern Saudi Arabia, using Sabouraud dextrose agar (SDA) which was incubated aerobically for up to three weeks at 30{degrees}C. Isolated fungi were initially identified using classical mycological tools and confirmed by sequence analysis of the large subunit ribosomal RNA gene. Cultured specimens from humans and geckos revealed phenotypically similar zygomycete-like fungi which conform to those of Basidiobolus species. The strains formed a monophyletic clade in the 28S ribosomal RNA gene phylogenetic tree. They shared 99.97% similarity with B. haptosporus and 99.97% with B. haptosporus var. minor but have a relatively remote similarity to B. ranarum (99.925%). One isolates from a gecko (L3) fall within the sub-clade encompassing B. haptosporus strain NRRL28635. The study strongly suggests a new and a serious causal agent of GIB related to Basidiobolus haptosporus. The isolation of identical Basidiobolus haptosporus-like strains from humans and lizards from one area is an important step towards identifying risk factors for GIB. Research is underway to screen more environmental niches and fully describe the Basidiobolus strains.

epidemiology↗

bioRxiv2018

Positively interacting strains that circulate in a network structured population induce cycling epidemics of Mycoplasma Pneumoniae

In many countries Mycoplasma pneumoniae (MP) epidemics last approximately one to two years and occur every three to seven years. Poor understanding of the drivers of recurrent MP epidemics limits the predictability of and dynamic responses to the outbreak. Taking into account network structured contacts among people and co-circulating strains of MP, we propose a multi-strain SIRS network model of epidemics of MP where different strains interact during re-infection and within secondary infection. Simulations show that although strain interactions and network-mediated spatial correlations are two separate mechanisms for MP epidemics cycling, each requires very restricted model parameter values such as strong strain interactions and strong network contacts, respectively. When both mechanisms work collectively, MP recurrent epidemics become feasible within the plausible ranges of model parameters. This indicates that positively interacting strains that co-circulate within network contacts induce periodicity and dominant strain shift in observed MP incidence.

epidemiology↗

bioRxiv2018

Exploring how generation intervals link strength and speed of epidemics

Infectious-disease outbreaks are often characterized by the reproductive number and exponential rate of growth r. provides information about out-break control and predicted final size. Directly estimating is difficult, while r can often be estimated from incidence data. These quantities are linked by the generation interval - the time between when an individual is infected by an infector, and when that infector was infected. It is often infeasible to ob-tain the exact shape of a generation-interval distribution, and to understand how this shape affects estimates of . We show that estimating generation interval mean and variance provides insight into the relationship between and r. We use examples based on Ebola, rabies and measles to explore approximations based on gamma-distributed generation intervals, and find that use of these simple approximations are often sufficient to capture the r- relationship and provide robust estimates of .

epidemiology↗

bioRxiv2018

A direct comparison of four high risk human papilloma virus tests versus the cobas test for detecting cervical intraepithelial neoplasia and cervical cancer

This study is to evaluate performances and genotyping capabilities of four human papilloma virus (HR-HPV) tests based on real-time polymerase chain reaction (PCR) technology platforms compared with the cobas test. Discordant results were further analyzed using INNO-LiPA HPV genotyping test, the gold standard laboratory test to determine presence and type of HPV infection. Over 200 samples from Hospital patients were collected and analyzed using five HR-HPV tests. Women with positive test results were referred directly to colposcopy. If a positive result was returned, biopsies were administered for pathological classification. Clinical performances and genotyping capabilities between the four HR-HPV and cobas tests were compared and contrasted. High levels of agreement were observed, though all HR-HPV tests presented discrepancies compared with the cobas test. Cervical intraepithelial neoplasia Grade 2 or higher lesions (CIN2+) was set as the threshold, and all five tests performed with equally high sensitivity. Lower levels of specificity were observed across all five tests. Results suggest the four HR-HPV tests analyzed are as effective as the cobas test in genotyping capacities and diagnosing CIN. Therefore, these test kits should be used for HPV screening, especially in developing nations because they are cost effective and reliable. Minor discrepancies between tests are generally unavoidable though this may add complexity to the clinical decision-making process. As such, we recommend that efforts be made to standardize HPV genotyping tests as well as to optimize clinical sensitivity and specificity. Focusing on these issues will drive the development of HPV detection techniques, therefore save lives.

epidemiology↗

bioRxiv2018

Heuristic optimisation of the management strategy of a plant epidemic using sequential sensitivity analyses

O_LIOptimisation of management strategies of epidemics is often limited by constraints on experiments at large spatiotemporal scales. A promising approach consists in modelling the biological epidemic process and human interventions, which both impact disease spread. However, few methods enable the simultaneous optimisation of the numerous parameters of sophisticated control strategies. To do so, we propose a heuristic approach based on sequential use of sensitivity analysis. This work is motivated by sharka (caused by Plum pox virus), a vector-borne disease of prunus trees (especially apricot, peach and plum), and its management in orchards, mainly based on surveillance and tree removal.\nC_LIO_LIOur approach is based on three sensitivity analyses which respectively aim to: i) identify the key parameters of a spatiotemporal model simulating disease spread and control; ii) approach optimal values for the key parameters; iii) refine the optimisation.\nC_LIO_LIWe highlight the importance of carefully designing the removal procedure, and propose improved strategies with regard to an economic criterion accounting for both the cost of the different control measures and the benefit generated by productive trees.\nC_LIO_LIWe expect that our general approach will help policymakers to design sustainable and cost-effective strategies for the management of infectious diseases.\nC_LI

epidemiology↗

bioRxiv2018

Spatial gene-by-environment mapping for schizophrenia reveals locale of upbringing effects beyond urban-rural differences

Identification of mechanisms underlying the incidence of psychiatric disorders has been hampered by the difficulty in discovering highly-predictive environmental risk factors. For example, prior efforts have failed to establish environmental effects predicting geospatial clustering of schizophrenia incidence beyond urban-rural differences. Here, we employ a novel statistical framework for decomposing the geospatial risk for schizophrenia based on locale of upbringing (place of residence, ages 0-7 years) and its synergistic effects with genetic liabilities (polygenic risk for schizophrenia). We use this statistical framework to analyze unprecedented geolocation and genotyping data in a case-cohort study of n=24,028 subjects, drawn from the 1.47 million Danish persons born between 1981 and 2005. Using this framework we estimate the effects of upbringing locale (E) and gene-by-locale interactions (GxE). After controlling for potential confounding variables, upbringing at high-risk locales increases the risk for schizophrenia on average by 122%, while GxE modulates genetic risk for schizophrenia on average by 78%. Within the boundaries of Copenhagen (the largest and most densely populated city of Denmark) specific locales vary substantially in their E and GxE effects, with hazard ratios ranging from 0.26 to 9.26 for E and from 0.20 to 5.95 for GxE. This study provides insight into the degree of geospatial clustering of schizophrenia risk, and our novel analytic procedure provides a framework for decomposing variation in geospatial risk into G, E, and GxE components.

epidemiology↗

bioRxiv2018

Iodine status of children and Knowledge, Attitude, Practice of Iodised salt use in a remote community in Kerema district, Gulf province, Papua New Guinea

Iodine deficiency is the single most common cause of preventable mental impairment in communities with suboptimal iodine intake. Objective of the present study was to assess in more detail the iodine status and knowledge, attitudes and practice (KAP) relating to use of iodised salt in a remote community in Kotidanga area, Kerema district, Gulf province, Papua New Guinea. This prospective school and community based cross-sectional study was carried out in 2017. Simple random sampling was used to select schools. Multistage sampling was used to randomly select 291 children aged 6 to 12 years. Salt samples were collected for analysis from childrens households as well as a single urine sample of selected children. Salt iodine content and Urinary iodine concentration (UIC) were analysed. A semi-structured FAO questionnaire was used to assess KAP of three different community groups. Only 64% of households had salt on the day of data collection. Mean iodine content in household salt samples was 29.0 {+/-} 19.1 ppm. Iodine content was below 30.0 ppm in 54.8% and below 15.0 ppm in 31.2% of salt samples. Mean per capita discretionary intake of household salt was 2.9 {+/-} 1.8 g/day. Median UIC was 25.5 g/L and Interquartile Range was 15.0 to 47.5 g/L; 75.9% (221/291) of the children had UIC below 50.0 g/L, indicating moderate status iodine nutrition. Median UIC was 34.3g/L for children in households with salt, compared to 15.5 g/L for children in households without salt, indicating severe iodine deficiency in the latter group. The three community groups had limited knowledge about importance of using iodised salt and consequences of iodine deficiency on health outcomes. This remote community has limited access to adequately iodised household salt due to high cost, inappropriate packaging, storage and food preparation, resulting in iodine deficiency. Strategies to increase iodine intake are needed.

epidemiology↗

bioRxiv2018

Facility ownership and mortality among older adults residing in care homes

Background and ObjectivesNursing or care home characteristics may have a long-term impact on the residents mortality risks that has not been studied previously. The studys main objective was to assess the association between facility ownership and long-term, all-cause mortality. Research Design and Methods. We conducted a mortality follow-up study on a cohort of 611 nursing-home residents in the city Madrid, Spain, from their 1998-1999 baseline interviews up to September 2013. Residents lived in three types of facilities: public, subsidized and private, which were also sub-classified according to size (number of beds). Residents information was collected by interviewing the residents themselves, their caregivers and facility physicians. We used time-to-event multivariable models and inverse probability weighting to estimate standardized mortality risk differences.\n\nResultsAfter a 3728 person-year follow-up (median/maximum of 4.8/15.2 years), 519 participants had died. In fully-adjusted models, the standardized mortality risk difference at 5 years of follow-up between large-sized public facilities and medium-sized private facilities was 18.9% (95% confidence interval [CI]: -33.4 to -4.5%), with a median survival (95% CI) of 3.6 (0.5 to 6.8) additional years. The fully-standardized 5-year mortality difference (95% CIs) comparing for-profit private facilities with not-for-profit public institutions was -15.1% (-31.1% to 0.9%), and the fully-standardized median survival difference (95% CIs) was 3.0 (-1.7 to 7.7) years.\n\nDiscussion and ImplicationsThese results are highly compatible with an effect on the long-term mortality risk for residents due to factors associated with the ownership of their facilities.

epidemiology↗

bioRxiv2018

Telomeres as integrative markers of exposure to stress and adversity: A systematic review and meta-analysis

Telomeres have been proposed as a biomarker that integrates the impacts of different kinds of stress and adversity into a common currency. There has as yet been no overall comparison of how different classes of exposure associate with telomeres. We present a meta-analysis of the literature relating telomere measures to stresses and adversities in humans. The analysed dataset contained 543 associations from 138 studies involving 402,116 people. Overall, there was a weak association between telomere variables and exposures (greater adversity, shorter telomeres: r = -0.15, 95% CI - 0.18 to -0.11). This was not driven by any one type of exposure, since significant associations were found separately for physical diseases, environmental hazards, nutrition, psychiatric illness, smoking, physical activity, psychosocial and socioeconomic exposures. Methodological features of the studies did not explain any substantial proportion of the heterogeneity in association strength. There was, however, evidence consistent with publication bias, with unexpectedly strong negative associations reported by studies with small samples. Restricting analysis to sample sizes greater than 100 attenuated the overall association substantially (r = -0.09, 95% CI -0.13 to -0.05). Most studies were underpowered to detect the typical association magnitude. The literature is dominated by cross-sectional and correlational studies which makes causal interpretation problematic.

epidemiology↗

bioRxiv2018

Examining food intake and eating out of home patterns among university students

Eating out of home (OH) is increasingly popular in Balkan countries, among them Albania. To date there is only anecdotal evidence regarding nutritional quality of food consumed OH and the contribution to diet. This study assessed intake of foods and drinks consumed OH and at home (AH), as well as their nutritional contribution to the daily diet of university students in Tirana, Albania. Using a single day Automated Multiple Pass Method (AMPM) 24-hour dietary recall, we examined food intake among 289 students aged 18-24 years old, from three major universities in Albania. Contribution of eating OH to total energy intake per day, as well as to daily consumption of macronutrients by eating OH intensity tertiles were assessed. Foods and drinks consumed OH contributed 46.9% [95%CI:41.4-52.8] of total daily energy intake, representing, on average, 1169.1kcal [95%CI:1088.3-1249.9]. Sweets, soft drinks and meat products were more frequently consumed OH, while fruits and vegetables consumption was extremely low. The average quantity of sugars and dietary fats per day was higher AH, 76.9g [95%CI:70.3-83.5] and 173.7g [95%CI:163.2-184.2] respectively, compared to OH, 33.7g [95%CI:30.4-37.0] and 142.0g [95%CI:131.5-152.5] respectively. Dietary composition of AH intake was richer in sugars, total fats and proteins, while OH intake was richer in saturated fats. The overall diet appeared unhealthy, when nutrients were assessed as energy percentage against WHO proposed nutrient standards for sugar and saturated fats. Eating OH, even though was associated with lower fruits and vegetables intake, was not clearly associated with poor diet quality, as AH foods were also characterized by increased saturated fats and sugars intake as energy percentage. This study provides data on the first assessment of current dietary patterns of the studied population and can be used as baseline for designing and conducting future studies and interventions targeting malnutrition in all its forms.

epidemiology↗

bioRxiv2018

Barriers and incentives for conducting research amongst the Ophthalmologists in Sub- Sahara Africa

BackgroundResearch is a critical component amongst the strategies to improve health outcomes of any country. The role of research assumes greater importance in Africa as it carries a larger share of global burden of diseases, blindness and low vision. \"Vision 2020- the Right to Sight\" is a WHO-IAPB collaborated initiative aiming to eliminate preventable blindness by the year 2020. High quality research in eye care is imperative for the initiative to succeed, however, there is a dearth of research in eye care in sub Saharan Africa in general and specifically in the Eastern, Central and Southern African (ECSA) region. Identifying the barriers that hamper research in this region is an important step towards elimination of preventable blindness.\n\nMethodsA structured questionnaire using the SurveyMonkey program was sent to ophthalmologists in the ECSA region and South Africa through their respective regional professional bodies. Data was analyzed using the SPSS program version.\n\nResultsLack of funding, inadequate time and poor research knowledge were the main research barriers while ability to improve eye health care through research was the main incentive for conducting research.\n\nConclusionThe barriers mainly center on financial, human and administrative infrastructure and resources. In spite of the barriers, ophthalmologists in the study region are enthusiastic in research aiming to increase evidence based knowledge to improve eye health care in line with the goals of \"Vision 2020- the Right to Sight\" initiative.

epidemiology↗

bioRxiv2018

Epigenetic selection and the DNA methylation signatures of adverse prenatal environments

Maternal adversity is associated with long-term physiological changes in offspring. These are believed to be mediated through epigenetic mechanisms, including DNA methylation (DNAm). Changes in DNAm are often interpreted as damage or as part of plastic responses of the embryo. We propose that selection on stochastic DNAm differences generated during epigenetic reprogramming after fertilization contributes to the effects of maternal adversity on DNAm. Using a mathematical model of epigenetic reprogramming in the early embryo we predict that this \"epigenetic selection\" will generate a characteristic reduction in variance of DNAm at selected loci in populations exposed to maternal adversity. We tested this prediction using DNAm data from a human cohort prenatally exposed to the Dutch Famine and confirmed the reduction in DNAm variance, suggesting that epigenetic selection may have occurred. Epigenetic selection should be considered as a possible mechanism linking adversity in pregnancy to offspring health and may have implications for the likely effectiveness of intervention strategies.

epidemiology↗

bioRxiv2018

Coronary artery disease risk and lipidomic profiles are similar in familial and population-ascertained hyperlipidemias

Aims: To characterize and compare coronary artery disease (CAD) risk and detailed lipidomic profiles of individuals with familial and population-ascertained hyperlipidemias.\n\nMethods and Results: We determined incident CAD risk for 760 members of 66 hyperlipidemic families ([≥] 2 first degree relatives with the same hyperlipidemia) and 19,644 Finnish FINRISK population study participants. We also quantified 151 lipid species in plasma or serum samples from 550 members of 73 hyperlipidemic pedigrees and 897 FINRISK participants using a mass spectrometric shotgun lipidomics platform. Hyperlipidemias (LDL-C or triacylglycerides over 90th population percentile) were associated with increased CAD risk (high LDL-C: HR 1.74, 95% CI 1.48-2.04; high triacylglycerides: HR 1.38, 95% CI 1.09-1.74) and the risk estimates were very similar between the family and population samples. High LDL-C was associated with altered levels of 105 lipid species in families (p-value range 0.033-7.3*10-20 at 5% false discovery rate) and 51 species in the population samples (p-value range 0.017-6.8*10-21). Hypertriglyceridemia was associated with altered levels of 117 lipid species in families (p-value range 0.035-1.8*10-49) and 119 species in the population sample (p-value range 0.038-2.3*10-56). The lipidomics profiles of hyperlipidemias were highly similar in families and population samples.\n\nConclusion: We identified distinct lipidomic profiles associated with high LDL-C and triacylglyceride levels. CAD risk, lipidomic profiles and genetic profiles are highly similar between familial and population-ascertained hyperlipidemias, providing evidence of similar and overlapping underlying mechanisms. Our results do not support different screening and treatment for such hyperlipidemias.

epidemiology↗

bioRxiv2018

Estimates for quality of life loss due to RSV

A number of vaccines against Respiratory Syncytial Virus (RSV) infection are approaching licensure. Deciding which RSV vaccine strategy, if any, to introduce, will partly depend on cost-effectiveness analyses, which compares the relative costs and health benefits of a potential vaccination programme. Health benefits are usually measured in Quality Adjusted Life Year (QALY) loss, however, there are no QALY loss estimates for RSV that have been determined using standardised instruments. Moreover, in children under the age of five years in whom severe RSV episodes predominantly occur, there are no appropriate standardised instruments to estimate QALY loss. We estimated the QALY loss due to RSV across all ages by developing a novel regression model which predicts the QALY loss without the use of standardised instruments. To do this, we conducted a surveillance study which targeted confirmed episodes in children under the age of five years (confirmed cases) and their household members who experienced symptoms of RSV during the same time (suspected cases.) All participants were asked to complete questions regarding their health during the infection, with the suspected cases aged 5-14 and 15+ years old additionally providing Health-Related Quality of Life (HR-QoL) loss estimates through completing EQ-5D-3L-Y and EQ-5D-3L instruments respectively. The questionnaire responses from the suspected cases were used to calibrate the regression model. The calibrated regression model then used other questionnaire responses to predict the HR-QoL loss without the use of EQ-5D instruments. The age-specific QALY loss was then calculated by multiplying the HR-QoL loss on the worst day predicted from the regression model, with estimates for the duration of infection from the questionnaires and a scaling factoring for disease severity. Our regression model for predicting HR-QoL loss estimates that for the worst day of infection, suspected RSV cases in persons five years and older who do and do not seek healthcare have an HR-QoL loss of 0{middle dot}616 (95% CI 0{middle dot}155-1{middle dot}371) and 0{middle dot}405 (95% CI 0{middle dot}111-1{middle dot}137) respectively. This leads to a QALY loss per RSV episode of 1{middle dot}950 x 10-3 (95% CI 0{middle dot}185 x 10-3 -9{middle dot}578 x 10-3) and 1{middle dot}543 x 10-3 (95% CI 0{middle dot}136 x 10-3 -6{middle dot}406 x 10-3) respectively. For confirmed cases in a child under the age of five years who sought healthcare, our model predicted a HR-QoL loss on the worst day of infection of 0{middle dot}820 (95% CI 0{middle dot}222-1{middle dot}450) resulting in a QALY loss per RSV episode of 3{middle dot}823 x 10-3 (95% CI 0{middle dot}492 x 10-3 -12{middle dot}766 x 10-3). Combing these results with previous estimates of RSV burden in the UK, we estimate the annual QALY loss of healthcare seeking RSV episodes as 1,199 for individuals aged five years and over and 1,441 for individuals under five years old. The QALY loss due to an RSV episode is less than the QALY loss due to an Influenza episode. These results have important implications for potential RSV vaccination programmes, which has so far focused on preventing infections in infants--where the highest reported disease burden lies. Future potential RSV vaccination programmes should also evaluate their impact on older children and adults, where there is a substantial but unsurveilled QALY loss.

epidemiology↗