Biostatistical Analysis of the Schistosomiasis Control Initiative Programme on Schistosoma Prevalence, Intensity and Associated Morbidity

Background: Schistosomiasis remains one of the most prevalent parasitic diseases in developing countries. Goal and objectives: The potential relationship between Schistosoma mansoni and anaemia, was examined using Schistosomiasis Control Initiative (SCI) data on Ugandan children and a randomized clinical trial implemented by colleagues from the London School of Hygiene and Tropical Medicine (LSHTM) in Western Kenya. The impact of large-scale administration of chemotherapy on Schistosoma haematobium infection and associated morbidity was also evaluated using SCI data on Burkinabe children. Evaluation and validation of field applicable tools, such as ultrasound, for the cost-effective diagnosis of schistosomiasis morbidity using SCI baseline data from Malian children was another aim of this thesis. Furthermore, in combination with the ultrasound scans, microscopic examination of urine for detection of S. haematobium eggs, dipsticks for detection of haematuria, tests for circulating antigens and serology tests were examined for the cost-effective assessment of S. haematobium prevalence in an adult’s dataset from Ghana. Methods: Biostatistical analysis of afore mentioned data was applied. Principal findings: Results from SCI and LSHTM studies suggest that anaemia is associated with schistosomiasis in African children, and that such anaemia shows a significant improvement following chemotherapy. Results from the SCI study in Burkina Faso suggested that even a single round of mass chemotherapy can have a substantial impact on S. haematobium infection and its associated morbidity in children. Microscopy and haematuria dipsticks were suggested as sensitive and specific indicators of prevalence of S. haematobium infection in Ghanaian adults. Furthermore, ultrasound global scores were demonstrated to be valuable markers in children for morbidity caused by S. haematobium infection, but ultrasonographic examination is not a reasonable substitute for microscopy or dipsticks for determining the prevalence of this infection. Significance: Finally, the key findings from all the studies presented, emphasizing how these relate to one another, are discussed

Pathways from maternal depression to young adult offspring depression: an exploratory longitudinal mediation analysis.

Maternal depression in the peri-natal period is associated with increased risk for young adult depression in offspring. This study explored mediation of these links via trajectories of child conduct and emotional problems (Strengths and Difficulties Questionnaire) from ages 4-16 years old in data from the Avon Longitudinal Study of Parents and Children cohort (n = 13373). Through gender-specific structural equation models, a composite measure of exposure to early maternal depression (Edinburgh Postnatal Depression Scale), predicted young adult depression at age 18 (Revised Clinical Interview Schedule - distal outcome). Mediational effects were then estimated by testing which parts of joint piecewise latent trajectory models for child/adolescent conduct and emotional problems were associated with both exposure and distal outcome. For girls, only conduct problems in early childhood were consistently indicated to mediate effects of early maternal depression on risk of young adulthood depression. Some evidence for a pathway via changing levels of childhood and adolescent emotional difficulties was also suggested. For boys, by contrast, the differing models gave less consistent findings providing some evidence for a small time-specific indirect effect via early childhood conduct problems. In addition to its practice implications the current methodological application offers considerable potential in exploratory longitudinal developmental mediation studies. © 2016 The Authors International Journal of Methods in Psychiatric Research Published by John Wiley & Sons Ltd

Opportunities and challenges for modelling epidemiological and evolutionary dynamics in a multihost, multiparasite system: Zoonotic hybrid schistosomiasis in West Africa

Multihost multiparasite systems are evolutionarily and ecologically dynamic, which presents substantial trans‐disciplinary challenges for elucidating their epidemiology and designing appropriate control. Evidence for hybridizations and introgressions between parasite species is gathering, in part in line with improvements in molecular diagnostics and genome sequencing. One major system where this is becoming apparent is within the Genus Schistosoma, where schistosomiasis represents a disease of considerable medical and veterinary importance, the greatest burden of which occurs in sub‐Saharan Africa. Interspecific hybridizations and introgressions bring an increased level of complexity over and above that already inherent within multihost, multiparasite systems, also representing an additional source of genetic variation that can drive evolution. This has the potential for profound implications for the control of parasitic diseases, including, but not exclusive to, widening host range, increased transmission potential and altered responses to drug therapy. Here, we present the challenging case example of haematobium group Schistosoma spp. hybrids in West Africa, a system involving multiple interacting parasites and multiple definitive hosts, in a region where zoonotic reservoirs of schistosomiasis were not previously considered to be of importance. We consider how existing mathematical model frameworks for schistosome transmission could be expanded and adapted to zoonotic hybrid systems, exploring how such model frameworks can utilize molecular and epidemiological data, as well as the complexities and challenges this presents. We also highlight the opportunities and value such mathematical models could bring to this and a range of similar multihost, multi and cross‐hybridizing parasites systems in our changing world

Physical activity and healthy ageing: A systematic review and meta-analysis of longitudinal cohort studies.

BACKGROUND: Older people constitute a significant proportion of the total population and their number is projected to increase by more than half by 2030. This increasing probability of late survival comes with considerable individual, economic and social impact. Physical activity (PA) can influence the ageing process but the specific relationship with healthy ageing (HA) is unclear. METHODS: We conducted a systematic review and meta-analysis of longitudinal studies examining the associations of PA with HA. Studies were identified from a systematic search across major electronic databases from inception as January 2017. Random-effect meta-analysis was performed to calculate a pooled effect size (ES) and 95% CIs. Studies were assessed for methodological quality. RESULTS: Overall, 23 studies were identified including 174,114 participants (30% men) with age ranges from 20 to 87 years old. There was considerable heterogeneity in the definition and measurement of HA and PA. Most of the identified studies reported a significant positive association of PA with HA, six reported a non-significant. Meta-analysis revealed that PA is positively associated with HA (ES: 1.39, 95% CI=1.23-1.57, n=17) even if adjusted for publication bias (ES: 1.27, 95% CI=1.11-1.45, n=20). CONCLUSIONS: There is consistent evidence from longitudinal observational studies that PA is positively associated with HA, regardless of definition and measurement. Future research should focus on the implementation of a single metric of HA, on the use of objective measures for PA assessment and on a full-range of confounding adjustment. In addition, our research indicated the limited research on ageing in low-and-middle income countries

Associations of smoking and alcohol consumption with healthy ageing: a systematic review and meta-analysis of longitudinal studies.

OBJECTIVES: The number of older people is growing across the world; however, quantitative synthesis of studies examining the impact of lifestyle factors on the ageing process is rare. We conducted a systematic review and meta-analysis of longitudinal studies to synthesise the associations of smoking and alcohol consumption with healthy ageing (HA). METHODS: Major electronic databases were searched from inception to March 2017 (prospectively registered systematic reviews registration number CRD42016038130). Studies were assessed for methodological quality. Random-effect meta-analysis was performed to calculate pooled ORs and 95% CI. RESULTS: In total, we identified 28 studies (n=184 543); 27 studies reported results on smoking, 22 on alcohol consumption. 23 studies reported a significant positive association of never or former smoking with HA and 4 non-significant. 12 studies reported a significant positive association of alcohol consumption with HA, 9 no association and 1 negative. Meta-analysis revealed increased pooled OR of HA for never smokers compared with current smokers (2.36, 95% CI 2.03 to 2.75), never smokers compared with former smokers (1.32, 95% CI 1.23 to 1.41), former or never smokers compared with current smokers (1.72, 95% CI 1.20 to 2.47), never smokers compared with past or current smokers (1.29, 95% CI 1.16 to 1.43); drinkers compared with non-drinkers (1.28, 95% CI 1.08 to 1.52), light drinkers compared with non-drinkers (1.12, 95% CI 1.03 to 1.22), moderate drinkers compared with non-drinkers (1.35, 95% CI 0.93 to 1.97) and high drinkers compared with non-drinkers (1.25, 95% CI 1.09 to 1.44). There was considerable heterogeneity in the definition and measurement of HA and alcohol consumption. CONCLUSIONS: There is consistent evidence from longitudinal studies that smoking is negatively associated with HA. The associations of alcohol consumption with HA are equivocal. Future research should focus on the implementation of a single metric of HA, on the use of consistent drinking assessment among studies and on a full-range of confounding adjustment. Our research also highlighted the limited research on ageing in low-and-middle-income countries

A strengthening evidence-base for mass deworming, but questions remain.

Soil-transmitted helminths, a group of three intestinal parasitic worms, are estimated to affect about a billion people worldwide, predominantly in low-income settings. The world's largest deworming programme is the lymphatic filariasis elimination programme, which combines community-wide treatment with drugs that target soil-transmitted helminths. As these programmes are scaled back because of successful control of lymphatic filariasis, the question of whether and how to continue or expand deworming for soil-transmitted helminths, usually delivered through school-based deworming programmes, remains to be answered

Healthy ageing and the prediction of mortality and incidence dependence in low- and middle- income countries: a 10/66 population-based cohort study.

BACKGROUND: In the absence of a consensus on definition and measurement of healthy ageing, we created a healthy ageing index tallying with the functional ability framework provided by the World Health Organization. To create this index, we employed items of functional ability and intrinsic capacity. The current study aims to establish the predictive validity and discrimination properties of this healthy ageing index in settings in Latin American, part of the 10/66 cohort. METHODS: Population-based cohort studies including 12,865 people ≥65 years old in catchment areas of Cuba, Dominican Republic, Venezuela, Mexico and Peru. We employed latent variable modelling to estimate the healthy ageing scores of each participant. We grouped participants according to the quintiles of the healthy ageing score distribution. Cox's proportional hazard models for mortality and sub-hazard (competing risks) models for incident dependence (i.e. needing care) were calculated per area after a median of 3.9 years and 3.7 years, respectively. Results were pooled together via fixed-effects meta-analysis. Our findings were compared with those obtained from self-rated health. RESULTS: Participants with lowest levels, compared to participants with highest level of healthy ageing, had increased risk of mortality and incident dependence, even after adjusting for sociodemographic and health conditions (HR: 3.25, 95%CI: 2.63-4.02; sub-HR: 5.21, 95%CI: 4.02-6.75). Healthy ageing scores compared to self-rated health had higher population attributable fractions (PAFs) for mortality (43.6% vs 19.3%) and incident dependence (58.6% vs 17.0%), and better discriminative power (Harrell's c-statistic: mortality 0.74 vs 0.72; incident dependence 0.76 vs 0.70). CONCLUSION: These results provide evidence that our healthy ageing index could be a valuable tool for prevention strategies as it demonstrated predictive and discriminative properties. Further research in other cultural settings will assist moving from a theoretical conceptualisation of healthy ageing to a more practical one

Development of a healthy ageing index in Latin American countries - a 10/66 dementia research group population-based study.

BACKGROUND: Our population is ageing and in 2050 more than one out of five people will be 60 years or older; 80% of whom will be living in a low-and-middle income country. Living longer does not entail living healthier; however, there is not a widely accepted measure of healthy ageing hampering policy and research. The World Health Organization defines healthy ageing as the process of developing and maintaining functional ability that will enable well-being in older age. We aimed to create a healthy ageing index (HAI) in a subset of six low-and-middle income countries, part of the 10/66 study, by using items of functional ability and intrinsic capacity. METHODS: The study sample included residents 65-years old and over (n = 12,865) from catchment area sites in Cuba, Dominican Republic, Peru, Venezuela, Mexico and Puerto Rico. Items were collected by interviewing participants or key informants between 2003 and 2010. Two-stage factor analysis was employed and we compared one-factor, second-order and bifactor models. The psychometric properties of the index, including reliability, replicability, unidimensionality and concurrent convergent validity as well as measurement invariance per ethnic group and gender were further examined in the best fit model. RESULTS: The bifactor model displayed superior model fit statistics supporting that a general factor underlies the various items but other subdomain factors are also needed. The HAI indicated excellent reliability (ω = 0.96, ωΗ = 0.84), replicability (H = 0.96), some support for unidimensionality (Explained Common Variance = 0.65) and some concurrent convergent validity with self-rated health. Scalar measurement invariance per ethnic group and gender was supported. CONCLUSIONS: A HAI with excellent psychometric properties was created by using items of functional ability and intrinsic capacity in a subset of six low-and-middle income countries. Further research is needed to explore sub-population differences and to validate this index to other cultural settings

Healthy ageing and the prediction of mortality and incidence dependence in low- and middle- income countries: a 10/66 population-based cohort study

Background: In the absence of a consensus on definition and measurement of healthy ageing, we created a healthy ageing index tallying with the functional ability framework provided by the World Health Organization. To create this index, we employed items of functional ability and intrinsic capacity. The current study aims to establish the predictive validity and discrimination properties of this healthy ageing index in settings in Latin American, part of the 10/66 cohort. Methods: Population-based cohort studies including 12,865 people ≥65 years old in catchment areas of Cuba, Dominican Republic, Venezuela, Mexico and Peru. We employed latent variable modelling to estimate the healthy ageing scores of each participant. We grouped participants according to the quintiles of the healthy ageing score distribution. Cox's proportional hazard models for mortality and sub-hazard (competing risks) models for incident dependence (i.e. needing care) were calculated per area after a median of 3.9 years and 3.7 years, respectively. Results were pooled together via fixed-effects meta-analysis. Our findings were compared with those obtained from self-rated health. Results: Participants with lowest levels, compared to participants with highest level of healthy ageing, had increased risk of mortality and incident dependence, even after adjusting for sociodemographic and health conditions (HR: 3.25, 95%CI: 2.63-4.02; sub-HR: 5.21, 95%CI: 4.02-6.75). Healthy ageing scores compared to self-rated health had higher population attributable fractions (PAFs) for mortality (43.6% vs 19.3%) and incident dependence (58.6% vs 17.0%), and better discriminative power (Harrell's c-statistic: mortality 0.74 vs 0.72; incident dependence 0.76 vs 0.70). Conclusion: These results provide evidence that our healthy ageing index could be a valuable tool for prevention strategies as it demonstrated predictive and discriminative properties. Further research in other cultural settings will assist moving from a theoretical conceptualisation of healthy ageing to a more practical one