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Projections show that the number of people above 60 years old will triple by 2050 in Mexico. Nevertheless, ageing is characterised by great variability in the health status. In this study, we aimed to identify trajectories of health and their associations with lifestyle factors in a national representative cohort study of older Mexicans. We used secondary data of 14,143 adults from the Mexican Health and Aging Study (MHAS). A metric of health, based on the conceptual framework of functional ability, was mapped onto four waves (2001, 2003, 2012, 2015) and created by applying Bayesian multilevel Item Response Theory (IRT). Conditional Growth Mixture Modelling (GMM) was used to identify latent classes of individuals with similar trajectories and examine the impact of physical activity, smoking and alcohol on those. Conditional on sociodemographic and lifestyle behaviour four latent classes were suggested: high-stable, moderate-stable, low-stable and decliners. Participants who did not engage in physical activity, were current or previous smokers and did not consume alcohol at baseline were more likely to be in the trajectory with the highest deterioration (i.e. decliners). This study confirms ageing heterogeneity and the positive influence of a healthy lifestyle. These results provide the ground for new policies.

Various global health initiatives are currently advocating the elimination of schistosomiasis within the next decade. Schistosomiasis is a highly debilitating tropical infectious disease with severe burden of morbidity and thus operational research accurately evaluating diagnostics that quantify the epidemic status for guiding effective strategies is essential. Latent class models (LCMs) have been generally considered in epidemiology and in particular in recent schistosomiasis diagnostic studies as a flexible tool for evaluating diagnostics because assessing the true infection status (via a gold standard) is not possible. However, within the biostatistics literature, classical LCM have already been criticised for real-life problems under violation of the conditional independence (CI) assumption and when applied to a small number of diagnostics (i.e. most often 3-5 diagnostic tests). Solutions of relaxing the CI assumption and accounting for zero-inflation, as well as collecting partial gold standard information, have been proposed, offering the potential for more robust model estimates. In the current article, we examined such approaches in the context of schistosomiasis via analysis of two real datasets and extensive simulation studies. Our main conclusions highlighted poor model fit in low prevalence settings and the necessity of collecting partial gold standard information in such settings in order to improve the accuracy and reduce bias of sensitivity and specificity estimates., Author summary Accurate schistosomiasis diagnosis is essential to assess the impact of large scale and repeated mass drug administration to control or even eliminate this disease. However, in schistosomiasis diagnostic studies, several inherent study design issues pose a real challenge for the currently available statistical tools used for diagnostic modelling and associated data analysis and conclusions. More specifically, those study design issues are: 1) the inclusion of small number of diagnostic tests (i.e. most often five), 2) non formal consensus about a schistosomiasis gold standard, 3) the contemporary use of relatively small sample sizes in relevant studies due to lack of research funding, 4) the differing levels of prevalence of the studied disease even within the same area of one endemic country and 5) other real world factors such as: the lack of appropriate equipment, the variability of certain methods due to biological phenomena and training of technicians across the endemic countries because of scarce financial resources contributing to the existing lack of a schistosomiasis gold standard. The current study aims to caution practitioners from blindly applying statistical models with small number of diagnostic tests and sample sizes, proposing design guidelines of future schistosomiasis diagnostic accuracy studies with recommendations for further research. While our study is centred around the diagnosis of schistosomiasis, we feel that the recommendations can be adapted to other major tropical infectious diseases as well.

Background Children are particularly susceptible to tuberculosis. However, most children exposed to Mycobacterium tuberculosis are able to control the pathogen without evidence of infection. Correlates of human protective immunity against tuberculosis infection are lacking, and their identification would aid vaccine design. Methods We recruited pairs of asymptomatic children with discordant tuberculin skin test status but the same sleeping proximity to the same adult with sputum smear-positive tuberculosis in a matched case-control study in The Gambia. Participants were classified as either Highly TB-Exposed Uninfected or Highly TB-Exposed Infected children. Serial luminescence measurements using an in vitro functional auto-luminescent Bacillus Calmette–Guerin (BCG) whole blood assay quantified the dynamics of host control of mycobacterial growth. Assay supernatants were analysed with a multiplex cytokine assay to measure associated inflammatory responses. Findings 29 pairs of matched Highly TB-Exposed Uninfected and Highly TB-Exposed Infected children aged 5 to 15 years old were enroled. Samples from Highly TB-Exposed Uninfected children had higher levels of mycobacterial luminescence at 96 hours than Highly TB-Exposed Infected children. Highly TB-Exposed Uninfected children also produced less BCG-specific interferon-γ than Highly TB-Exposed Infected children at 24 hours and at 96 hours. Interpretation Highly TB-Exposed Uninfected children showed less control of mycobacterial growth compared to Highly TB-Exposed Infected children in a functional assay, whilst cytokine responses mirrored infection status. Funding Clinical Research Training Fellowship funded under UK Medical Research Council/Department for International Development Concordat agreement and part of EDCTP2 programme supported by European Union (MR/K023446/1). Also MRC Program Grants (MR/K007602/1, MR/K011944/1, MC_UP_A900/1122).

Objective To describe the rates and risk factors for stillbirth and pre-discharge neonatal mortality (PDNM), and impact on quality of life (QoL) among women with postpartum hemorrhage (PPH). Methods A secondary analysis was conducted of the WOMAN trial, which evaluated the use of tranexamic acid for PPH and collected infant outcome data to assess drug safety. The analysis was restricted to singletons (n=18 942). Overall and country-level rates of stillbirth and PDNM were calculated. Multilevel logistic regression models examined the association of stillbirth and PDNM with selected risks, and the association of mother's QoL at discharge after stillbirth or PDNM. Results For women with PPH, the rate of stillbirths was 104.42 per 1000 births (n=1978) and the rate of PDNM was 15.56 per 1000 live births (n=264). Cesarean delivery, increasing blood loss, maternal complications, and maternal death were strongly associated with these adverse outcomes. Women with stillbirth and PDNM were significantly more likely to report poorer QoL. Conclusion Women with PPH experience an extremely high rate of stillbirth and slightly elevated PDNM, which is associated with markers of the severity of their condition and impacts on their QoL.

Background: Children are particularly susceptible to tuberculosis. However, most children exposed to Mycobacterium tuberculosis are able to control the pathogen without evidence of infection. Correlates of human protective immunity against tuberculosis infection are lacking, and their identification would aid vaccine design. Methods: We recruited pairs of asymptomatic children with discordant tuberculin skin test status but the same sleeping proximity to the same adult with sputum smear-positive tuberculosis in a matched case-control study in The Gambia. Participants were classified as either Highly Exposed Uninfected [HEU] or Highly Exposed Infected [HEI] children. Serial luminescence measurements using an in vitro functional auto-luminescent Bacillus Calmette–Guerin (BCG) whole blood assay quantified the dynamics of host control of mycobacterial growth. Assay supernatants were analysed with a multiplex cytokine assay to measure associated inflammatory responses. Findings: 29 pairs of matched HEI and HEU children aged 5 to 15 years old were enrolled. Samples from HEU children had higher levels of mycobacterial luminescence at 96H than HEI children. HEU children also produced less BCG-specific interferon-γ than HEI children at 24 hours and at 96 hours. Interpretation: HEI children showed superior control of mycobacterial growth compared to HEU children in a functional assay whilst cytokine responses mirrored infection status. Funding: Clinical Research Training Fellowship jointly funded by UK Medical Research Council (MRC) and UK Department for International Development (DFID) under MRC/DFID Concordat agreement and part of the EDCTP2 programme supported by the European Union (MR/K023446/1). Also enabled by MRC Program Grants (MR/K007602/1, MR/K011944/1, MC_UP_A900/1122). Declaration of Interests: BK holds a patent for a paediatric TB diagnostic biosignature. The authors do not have any other commercial or other association that might pose a conflict of interest. The data presented here form part of RB’s PhD thesis “Protection from Mycobacterium tuberculosis infection: Learning from exposed but uninfected children” awarded March 2018 by Imperial College London. Ethics Approval Statement: The study was approved by The Gambia Government/MRC Joint Ethics Committee (SCC1405 and SCC1273) and the Imperial College Healthcare Tissue Bank (R13071).

Sepsis and meningitis due to invasive group B Streptococcus (iGBS) disease during early infancy is a leading cause of child mortality. Recent systematic estimates of the worldwide burden of GBS suggested that there are 319,000 cases of infant iGBS disease each year, and an estimated 147,000 stillbirths and young-infant deaths, with the highest burden occurring in Sub-Saharan Africa. The following priority data gaps were highlighted: (1) long-term outcome data after infant iGBS, including mild disability, to calculate quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs) and (2) economic burden for iGBS survivors and their families. Geographic data gaps were also noted with few studies from low- and middle- income countries (LMIC), where the GBS burden is estimated to be the highest. In this paper we present the protocol for a multi-country matched cohort study designed to estimate the risk of long-term neurodevelopmental impairment (NDI), socioemotional behaviors, and economic outcomes for children who survive invasive GBS disease in Argentina, India, Kenya, Mozambique, and South Africa. Children will be identified from health demographic surveillance systems, hospital records, and among participants of previous epidemiological studies. The children will be aged between 18 months to 17 years. A tablet-based custom-designed application will be used to capture data from direct assessment of the child and interviews with the main caregiver. In addition, a parallel sub-study will prospectively measure the acute costs of hospitalization due to neonatal sepsis or meningitis, irrespective of underlying etiology. In summary, these data are necessary to characterize the consequences of iGBS disease and enable the advancement of effective strategies for survivors to reach their developmental and economic potential. In particular, our study will inform the development of a full public health value proposition on maternal GBS immunization that is being coordinated by the World Health Organization.

Neonatal invasive disease caused by Group B Streptococcus (GBS) is responsible for much acute mortality and long-term morbidity. To guide development of better prevention strategies, including maternal vaccines that protect neonates against GBS, it is necessary to estimate the burden of this condition globally and in different regions. Here, we present a Bayesian model that estimates country-specific invasive GBS (iGBS) disease incidence in children aged 0 to 6 days. The model combines different types of epidemiological data, each of which has its own limitations: GBS colonization prevalence in pregnant women, risk of iGBS disease in children born to GBS-colonized mothers and direct estimates of iGBS disease incidence where available. In our analysis, we present country-specific maternal GBS colonization prevalence after adjustment for GBS detection assay used in epidemiological studies. We then integrate these results with other epidemiological data and estimate country-level incidence of iGBS disease including in countries with no studies that directly estimate incidence. We are able to simultaneously estimate two key epidemiological quantities: the country-specific incidence of early-onset iGBS disease, and the risk of iGBS disease in babies born to GBS-colonized women. Overall, we believe our method will contribute to a more comprehensive quantification of the global burden of this disease, inform cost-effectiveness assessments of potential maternal GBS vaccines and identify key areas where data are necessary., Author summary Invasive disease caused by Group B Streptococcus (GBS) in young infants continues to be a major public health problem in both developed and developing countries. However, data on the incidence of this infection during the first week of life are only available for a small number of countries, which has complicated the quantification of the burden of this disease globally. In this paper, we develop a Bayesian framework to estimate the incidence of invasive GBS infection that combines data from multiple types of epidemiological studies, with adjustment for relevant factors such as diagnostic methods used in the studies. We present estimates from a series of models, and our results highlight the potential weaknesses of different types of studies and the importance to consider the entire evidence when estimating global burden of invasive neonatal infections. We believe this model is a step toward better quantification of the number of cases in different regions.

The number of people above 60 years old will double by 2050. There is a considerate variability in the health status of older people. The identification of the different trajectories that people follow as they grow older constitutes one of the aims of the ATHLOS project. In the current study, we created a metric of health in the four available waves (2001, 2003, 2012, 2015) of the Mexican Health and Aging Study (MHAS) by employing Bayesian multilevel Item Response Theory. Growth mixture modelling indicated that older Mexicans (n=14,143) age by following four distinct pathways (i.e. high-stable, moderate-stable, low-stable, decliners). Adherence to healthy lifestyle behaviours (i.e. physical activity, non-smoking, limited alcohol consumption) was associated with better health trajectories. Preliminary analyses in the ATHLOS harmonised dataset also suggest that older people age by following four distinct pathways. The impact of lifestyle behaviours within the harmonised dataset will be investigated and also presented.

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.

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., This work is also supported by the ATHLOS (Ageing Trajectories of Health: Longitudinal Opportunities and Synergies) project, funded by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement number 635316. A. M. P. was supported by the MRC MR/K021907/1

For epidemiological work with soil transmitted helminths the recommended diagnostic approaches are to examine fecal samples for microscopic evidence of the parasite. In addition to several logistical and processing issues, traditional diagnostic approaches have been shown to lack the sensitivity required to reliably identify patients harboring low-level infections such as those associated with effective mass drug intervention programs. In this context, there is a need to rethink the approaches used for helminth diagnostics. Serological methods are now in use, however these tests are indirect and depend on individual immune responses, exposure patterns and the nature of the antigen. However, it has been demonstrated that cell-free DNA from pathogens and cancers can be readily detected in patient’s urine which can be collected in the field, filtered in situ and processed later for analysis. In the work presented here, we employ three diagnostic procedures—stool examination, serology (NIE-ELISA) and PCR-based amplification of parasite transrenal DNA from urine–to determine their relative utility in the diagnosis of S. stercoralis infections from 359 field samples from an endemic area of Argentina. Bayesian Latent Class analysis was used to assess the relative performance of the three diagnostic procedures. The results underscore the low sensitivity of stool examination and support the idea that the use of serology combined with parasite transrenal DNA detection may be a useful strategy for sensitive and specific detection of low-level strongyloidiasis. Fil: Krolewiecki, Alejandro Javier. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Koukounari, Artemis. Liverpool School of Tropical Medicine; Reino Unido Fil: Romano, Miryam de Los Angeles. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. University Johns Hopkins; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Caro, Reynaldo N.. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina Fil: Scott, Alan L. University Johns Hopkins; Estados Unidos Fil: Fleitas, Pedro Emanuel. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Cimino, Rubén Oscar. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Shiff, Clive J.. University Johns Hopkins; Estados Unidos

Latin American and the Caribbean countries exhibit high life expectancy and projections show that they will experience the fastest growth of older people in the following years. As people live longer, it is important to maximise the opportunity to age healthily. We aimed to examine the associations of lifestyle behaviours with healthy ageing in Cuba, Dominican Republic, Peru, Mexico and Puerto Rico, part of the 10/66 study. Residents 65 years old and over (n = 10,900) were interviewed between 2003 and 2010. In the baseline survey, we measured four healthy behaviours: Physical activity, non-smoking, moderate drinking and fruits or vegetables consumption. Healthy ageing was conceptualised within the functional ability framework over a median of 4 years follow-up. Logistic models were calculated per country and then pooled together with fixed-effects meta-analysis. People engaging in physical activity and consuming fruits or vegetables had increased odds of healthy ageing in the follow-up (OR: 2.59, 95% CI: 2.20&ndash, 3.03, OR: 1.24, 95% CI: 1.06&ndash, 1.44, respectively). Compared with participants engaging in none or one healthy behaviour, the ORs of participants engaging in two, three or four healthy behaviours increased in a linear way (OR: 1.60, 95% CI: 1.40&ndash, 1.84, OR: 2.29, 95% CI: 1.94&ndash, 2.69, OR: 2.46, 95% CI: 1.54&ndash, 3.92, respectively). Our findings highlight the importance of awareness of a healthy lifestyle behaviour among older people.

(1) Background: Current international policy for schistosomiasis and soil-transmitted helminthiasis (STH) control emphasises mass administration of deworming drugs in school-based programmes. However, this approach is insufficient to control the transmission of these diseases, and their burden in non-school cohorts is recognised, albeit under-researched. This research will investigate the feasibility and acceptability of expanding access to praziquantel (PZQ) against schistosomiasis, and albendazole (ALB) against STH, to communities in selected transmission settings in Ghana. (2) Methods: A three-site longitudinal study will be implemented to investigate the effectiveness of expanding treatment strategies for PZQ and ALB to community members. In the context of community mass drug administration (to preschool children, school non-attending children, and adults, including pregnant women), the intervention will be assessed in a random sample of community members, at baseline with follow-up at 6, 12, and 18 months. In each community, 658 participants will be enrolled, and 314 followed up at each time point. The primary outcome measure is the prevalence of infection of Schistosoma haematobium and/or S. mansoni at study endpoint, as assessed by longitudinal surveys. Secondary outcomes are to quantify the infection of schistosomiasis and STH infections in non-treated cohorts, reductions in prevalence of STH, and intensity of schistosomiasis and STH, and treatment coverage. Nested within this study will be qualitative, cost-benefit, and cost-effectiveness evaluations that will explore accessibility, feasibility, and economic impact of expanded treatment from different complementary perspectives. (3) Discussion: Using a multidisciplinary approach, this study will generate evidence for improved availability, acceptability, affordability, and accessibility to deworming drugs against schistosomiasis and STH to individuals and communities in Ghana. This is likely to have considerable research, programmatic, and political value to contribute evidence for national programme policy development within Ghana, and, more broadly, World Health Organization policy development.

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.

Two schistosome species--Schistosoma haematobium and S. mansoni--with two very different pathological profiles (urogenital versus intestinal), are responsible for the majority of human schistosomiasis infections across sub-Saharan Africa. The aim of this study was to determine whether coinfections have an impact on species-specific morbidity measures when compared to single species infections. Children from two neighbouring schools in Taveta, Kenya were grouped by infection status, i.e. uninfected, single species infections or coinfected. Clinical examination of the liver and spleen by palpation was performed and urinary albumin levels were recorded at baseline and at 12 months after praziquantel administration. Additional ultrasonographic profiles of the children's liver, spleen and bladder were incorporated at follow-up. It was found that S. haematobium-associated urogenital morbidity was lower in the coinfected group relative to single S. haematobium infections, even when infection intensities were taken into account. We also observed an association between S. haematobium infection and liver (intestinal-associated) morbidity regardless of coinfections. The findings reported here suggest that further research should be performed on the impact of S. haematobium infections on liver morbidity as well as to determine the impact of mixed schistosome species infections on human morbidity outcomes across different endemic settings.

In disease control or elimination programs, diagnostics are essential for assessing the impact of interventions, refining treatment strategies, and minimizing the waste of scarce resources. Although high-performance tests are desirable, increased accuracy is frequently accompanied by a requirement for more elaborate infrastructure, which is often not feasible in the developing world. These challenges are pertinent to mapping, impact monitoring, and surveillance in trachoma elimination programs. To help inform rational design of diagnostics for trachoma elimination, we outline a nonparametric multilevel latent Markov modeling approach and apply it to 2 longitudinal cohort studies of trachoma-endemic communities in Tanzania (2000-2002) and The Gambia (2001-2002) to provide simultaneous inferences about the true population prevalence of Chlamydia trachomatis infection and disease and the sensitivity, specificity, and predictive values of 3 diagnostic tests for C. trachomatis infection. Estimates were obtained by using data collected before and after mass azithromycin administration. Such estimates are particularly important for trachoma because of the absence of a true "gold standard" diagnostic test for C. trachomatis. Estimated transition probabilities provide useful insights into key epidemiologic questions about the persistence of disease and the clearance of infection as well as the required frequency of surveillance in the post-elimination setting.

International audience; BACKGROUND: The global impact of the 2009 influenza A(H1N1) pandemic (H1N1pdm) is not well understood. OBJECTIVES: We estimate overall and age-specific prevalence of cross-reactive antibodies to H1N1pdm virus and rates of H1N1pdm infection during the first year of the pandemic using data from published and unpublished H1N1pdm seroepidemiological studies.METHODS: Primary aggregate H1N1pdm serologic data from each study were stratified in standardized age groups and evaluated based on when sera were collected in relation to national or subnational peak H1N1pdm activity. Seropositivity was assessed using well-described and standardized hemagglutination inhibition (HI titers ≥ 32 or ≥ 40) and microneutralization (MN ≥ 40) laboratory assays. The prevalence of cross-reactive antibodies to the H1N1pdm virus was estimated for studies using sera collected prior to the start of the pandemic (between 2004 and April 2009); H1N1pdm cumulative incidence was estimated for studies in which collected both pre- and post-pandemic sera; and H1N1pdm seropositivity was calculated from studies with post-pandemic sera only (collected between December 2009-June 2010).RESULTS: Data from 27 published/unpublished studies from 19 countries/administrative regions - Australia, Canada, China, Finland, France, Germany, Hong Kong SAR, India, Iran, Italy, Japan, Netherlands, New Zealand, Norway, Reunion Island, Singapore, United Kingdom, United States, and Vietnam - were eligible for inclusion. The overall age-standardized pre-pandemic prevalence of cross-reactive antibodies was 5% (95%CI 3-7%) and varied significantly by age with the highest rates among persons ≥ 65 years old (14% 95%CI 8-24%). Overall age-standardized H1N1pdm cumulative incidence was 24% (95%CI 20-27%) and varied significantly by age with the highest in children 5-19 (47% 95%CI 39-55%) and 0-4 years old (36% 95%CI 30-43%).CONCLUSIONS: Our results offer unique insight into the global impact of the H1N1 pandemic and highlight the need for standardization of seroepidemiological studies and for their inclusion in pre-pandemic preparedness plans. Our results taken together with recent global pandemic respiratory-associated mortality estimates suggest that the case fatality ratio of the pandemic virus was approximately 0.02%.

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

SUMMARYSchistosomiasis remains one of the most prevalent parasitic diseases in developing countries. After malaria, schistosomiasis is the most important tropical disease in terms of human morbidity with significant economic and public health consequences. Although schistosomiasis has recently attracted increased focus and funding for control, it has been estimated that less than 20% of the funding needed to control the disease in Africa is currently available. In this article the following issues are discussed: the rationale, development and objectives of the Schistosomiasis Control Initiative (SCI)-supported programmes; the management approaches followed to achieve implementation by each country; mapping, monitoring and evaluation activities with quantifiable impact of control programmes; monitoring for any potential drug resistance; and finally exit strategies within each country. The results have demonstrated that morbidity due to schistosomiasis has been reduced by the control programmes. While challenges remain, the case for the control of schistosomiasis has been strengthened by research by SCI teams and the principle that a national programme using ‘preventive chemotherapy’ can be successfully implemented in sub-Saharan Africa, whenever the resources are available. SCI and partners are now actively striving to raise further funds to expand the coverage of integrated control of neglected tropical diseases (NTDs) in sub-Saharan Africa.

SUMMARYA primary objective of schistosomiasis control programmes is to achieve, and hence also demonstrate, a quantifiable reduction in schistosome-associated morbidity as a consequence of chemotherapeutic intervention. Inherent within such an objective, it is necessary to define and validate direct and indirect indicators of schistosome-related morbidity. However, to define and thereby document such morbidity, and its reduction following treatment, may not be straightforward, particularly for intestinal schistosomiasis-induced morbidity, which is often not apparent in all but the most severe or chronic cases. Within all ‘Schistosomiasis Control Initiative’ activities, across selected sub-Saharan African countries since 2002, a range of standard and novel potential morbidity markers have been monitored and evaluated. Parasitological intensity measures, combined with haemoglobin/anaemia counts and ultrasonography, proved valuable schistosomiasis-related morbidity indicators, being both logistically practical and informative. Additional measures tested, such as albumin excretion profiles, were promising, and are subject to ongoing research, whilst some measures, such as distended stomach/umbilical circumference, anthropometrics and health questionnaires proved less reliable. These results serve to both illustrate the success of current control activities in reducing schistosome-induced morbidity, and to highlight key tools and techniques for continued application within ongoing and future mass drug administration programmes.

Substantial uncertainties surround the sensitivities and specificities of diagnostic techniques for urinary schistosomiasis. We used latent class (LC) modeling to address this problem. In this study, 220 adults in three villages northwest of Accra, Ghana were examined using five Schistosoma haematobium diagnostic measures: microscopic examination of urine for detection of S. haematobium eggs, dipsticks for detection of hematuria, tests for circulating antigens, antibody tests, and ultrasound scans of the urinary system. Testing of the LC model indicated non-invariance of the performance of the diagnostic tests across different age groups, and measurement invariance held for males and females and for the three villages. We therefore recommend the use of LC models for comparison between and the identification of the most accurate schistosomiasis diagnostic tests. Furthermore, microscopy and hematuria dipsticks were indicated through these models as the most appropriate techniques for detection of S. haematobium infection.

The potential relationship between Schistosoma mansoni and anemia was examined using data obtained by the Schistosomiasis Control Initiative (SCI) before (baseline) and 1 year after (follow-up) a chemotherapeutic treatment program in Uganda. Changes in hemoglobin (Hb) levels in 2,788 children in relation to their schistosomiasis and/or hookworm infection intensity category and baseline anemia status were analyzed. At baseline, significant predictors of childhood anemia were intensities of S. mansoni and hookworm infection. At follow-up, moderate or heavy hookworm as well as heavy S. mansoni infections were important. Children heavily infected with S. mansoni or hookworm had significantly lower Hb counts at baseline compared with those not infected. Among anemic children at the baseline survey, a significant increase in Hb counts of 0.834 g/dL after treatment was found. Our results suggest that anemia is associated with schistosomiasis and hookworm in Ugandan children and that such anemia shows a significant improvement after chemotherapy.

Regular treatment with praziquantel (PZQ) is the strategy for human schistosomiasis control aiming to prevent morbidity in later life. With the recent resolution on schistosomiasis elimination by the 65th World Health Assembly, appropriate diagnostic tools to inform interventions are keys to their success. We present a discrete Markov chains modelling framework that deals with the longitudinal study design and the measurement error in the diagnostic methods under study. A longitudinal detailed dataset from Uganda, in which one or two doses of PZQ treatment were provided, was analyzed through Latent Markov Models (LMMs). The aim was to evaluate the diagnostic accuracy of Circulating Cathodic Antigen (CCA) and of double Kato-Katz (KK) faecal slides over three consecutive days for Schistosoma mansoni infection simultaneously by age group at baseline and at two follow-up times post treatment. Diagnostic test sensitivities and specificities and the true underlying infection prevalence over time as well as the probabilities of transitions between infected and uninfected states are provided. The estimated transition probability matrices provide parsimonious yet important insights into the re-infection and cure rates in the two age groups. We show that the CCA diagnostic performance remained constant after PZQ treatment and that this test was overall more sensitive but less specific than single-day double KK for the diagnosis of S. mansoni infection. The probability of clearing infection from baseline to 9 weeks was higher among those who received two PZQ doses compared to one PZQ dose for both age groups, with much higher re-infection rates among children compared to adolescents and adults. We recommend LMMs as a useful methodology for monitoring and evaluation and treatment decision research as well as CCA for mapping surveys of S. mansoni infection, although additional diagnostic tools should be incorporated in schistosomiasis elimination programs., Author Summary Schistosomiasis remains one of the most prevalent parasitic diseases in developing countries, with Schistosoma mansoni being the most widespread of the human-infecting schistosomes. For the routine surveillance of human S. mansoni infection more “field-applicable,” sensitive, and cost-effective diagnostics that replicate faecal samples over several consecutive days [the Kato-Katz (KK) method], are needed. We propose a statistical modelling framework in order to evaluate the diagnostic performance of the urine strip test for Circulating Cathodic Antigen (CCA) and single-day double KK measurements over three consecutive days for the diagnosis of S. mansoni infection in two different age groups from Uganda pre- and post- praziquantel (PZQ) treatment. We demonstrate that CCA is an appropriate tool for mapping surveys of S. mansoni infection. Our findings should allow for evaluation of the risk of potential misinterpretation with regards to diagnosis of S. mansoni infection through CCA or KK in this endemic setting pre- and post- PZQ treatment as the numbers and infection intensities are brought down, bridging existing important gaps in schistosomiasis diagnostics research. More generally, the proposed statistical analysis can reveal important biological insights from other diseases without gold standard diagnostic tools whenever longitudinal data are available.

JX; Chen, JH; Churcher, TS; Drakeley, CJ; Edwards, T; Fenwick, A; French, M; Gabrielli, AF; Grassly, NC; Harding-Esch, EM; Holland, MJ; Koukounari, A; Lammie, PJ; Leslie, J; Mabey, DC; Rhajaoui, M; Secor, WE; Stothard, JR; Wei, H; Willingham, AL; Zhou, XN; Peeling, RW (2012) A diagnostics platform for the integrated mapping, monitoring, and surveillance of neglected tropical diseases: rationale and target product profiles. PLoS neglected tropical diseases, 6 (7). e1746. ISSN 1935-2727

Background Diagnosis of urogenital schistosomiasis in chronically infected adults is challenging but important, especially because long term infection of the bladder and urinary tract can have dire consequences. We evaluated three tests for viable infection: detection of parasite specific DNA Dra1 fragments, haematuria and presence of parasite eggs for sensitivity (Se) and specificity (Sp). Methods Over 400 urine specimens collected from adult volunteers in an endemic area in Western Nigeria were assessed for haematuria then filtered in the field, the filter papers dried and later examined for eggs and DNA. The results were stratified according to sex and age and subjected to Latent Class analysis. Conclusions Presence of Dra1 in males (Se = 100%; Sp = 100%) exceeded haematuria (Se = 87.6%: Sp = 34.7%) and detection of eggs (Se = 70.1%; Sp = 100%). In females presence of Dra1 was Se = 100%: Sp = 100%, exceeding haematuria (Se = 86.7%: Sp = 77.0%) and eggs (Se = 70.1%; Sp = 100%). Dra1 became undetectable 2 weeks after praziquantel treatment. We conclude detection of Dra1 fragment is a definitive test for the presence of Schistosoma haematobium infection., Author Summary The definitive test for schistosomiasis has been to detect parasite eggs in excreta. This is effective in children but as people age, it is difficult to find the eggs in spite of suspicion of infection. It also implies that adults have thrown off the infection, and therefore the infection is mainly one of children. However this is not the case as adults with chronic infections can develop severe bladder infection that can progress to bladder cancer. In clinical situations a sensitive test for urogenital schistosomiasis is important. We have recently shown that it is possible to detect schistosome species-specific DNA in urine, even in the absence of eggs in excreta. Here we use latent class analysis to compare sensitivity and specificity of three test procedures, haematuria, eggs in urine and specific DNA in urine in the absence of a gold standard. We show that the latter test is extremely promising for the diagnosis of urogenital schistosomiasis and should also be useful in field studies as it will be able to reveal infections in people frequently presumed to be uninfected. This new test indicated the presence of schistosomes in 10.7% of adults who did not pass eggs in urine specimens.

Background Over 1 billion of the world's poorest inhabitants are afflicted by neglected tropical diseases (NTDs). Integrated control programmes aimed at tackling these debilitating NTDs have been recently initiated, mainly using preventative chemotherapy. Monitoring and evaluation (M&E) of these integrated programs presents particular challenges over and above those required for single disease vertical programmes. We used baseline data from the National NTD Control Programme in Burkina Faso in order to assess the feasibility of an integrated survey design, as well as to elucidate the contribution of environmental variables to the risk of either Schistosoma haematobium, trachoma, or both among school-aged children. Methods S. haematobium infection was diagnosed by detecting eggs in urine. A trachoma case was defined by the presence of Trachomatous inflammation-Follicular (TF) and/or Trachomatous inflammation-Intense (TI) in either eye. Baseline data collected from 3,324 children aged 7-11 years in 21 sentinel sites across 11 regions of Burkina Faso were analyzed using simple and multivariable hierarchical binomial logistic regression models fitted by Markov Chain Monte Carlo estimation methods. Probabilities of the risk of belonging to each infection/disease category were estimated as a function of age, gender (individual level), and environmental variables (at sentinel site level, interpolated from national meteorological stations). Results Overall prevalence at the sentinel sites was 11.79% (95% CI: 10.70-12.89) for S. haematobium; 13.30% (12.14-14.45) for trachoma and 0.84% (0.53-1.15) for co-infections. The only significant predictor of S. haematobium infection was altitude. There were significant negative associations between the prevalence of active trachoma signs and minimum temperature, and air pressure. Conditional upon these predictors, these data are consistent with the two pathogens being independent. Conclusions Urogenital schistosomiasis and trachoma constitute public health problems in Burkina Faso. Sentinel site (at school level) surveys for these two NTDs can be implemented simultaneously. However, to support MDA treatment decisions in Burkina Faso, the protocol used in this study would only be applicable to hypoendemic trachoma areas. More research is needed to confirm if these findings can be generalized to West Africa and beyond.

Background In the developing world co-infections and polyparasitism within humans appear to be the rule rather than the exception, be it any combination of inter-specific and/or inter- and intra-Genera mixed infections. Mixed infections might generate synergistic or antagonistic interactions and thereby clinically affect individuals and/or impact parasite epidemiology. Methods The current study uniquely assesses both Schistosoma mansoni- and Schistosoma haematobium-related morbidity of the liver and the bladder as assessed by ultrasound as well as spleen and liver morbidity through clinical exams. The impact of praziquantel (PZQ) treatment on such potential inter-specific schistosome interactions and resulting morbidity using uniquely detailed longitudinal data (pre- and one year post-PZQ treatment) arising from the National Schistosomiasis Control Program in three areas of Mali: Ségou, Koulikoro and Bamako, is also evaluated. At baseline, data were collected from up to 2196 children (aged 7-14 years), 844 of which were infected with S. haematobium only, 124 with S. mansoni only and 477 with both. Follow-up data were collected from up to 1265 children. Results Results suggested lower liver morbidity in mixed compared to single S. mansoni infections and higher bladder morbidity in mixed compared to single S. haematobium infections. Single S. haematobium or S. mansoni infections were also associated with liver and spleen morbidity whilst only single S. haematobium infections were associated with bladder morbidity in these children (light S. haematobium infection OR: 4.3, p < 0.001 and heavy S. haematobium infection OR: 19, p < 0.001). PZQ treatment contributed to the regression of some of the forms of such morbidities. Conclusions Whilst the precise biological mechanisms for these observations remain to be ascertained, the results illustrate the importance of considering mixed species infections in any analyses of parasite-induced morbidity, including that for the proposed Disability Adjusted Life Years (DALYs) revised estimates of schistosomiasis morbidity.

SUMMARYSince 2004 the West African countries of Burkina Faso, Mali and Niger have implemented national schistosomiasis and soil-transmitted helminthiasis control programmes with financial and technical support from the Schistosomiasis Control Initiative (SCI). In the first three years of the control programmes, nearly 13·5 million doses of praziquantel and albendazole have been administered against schistosomiasis and soil-transmitted helminthiasis with coverage rates varying between 67·0% and 93·9%. These treatments have resulted in a reduction of the prevalence and intensity of Schistosoma infection in the sentinel cohorts that were set up to monitor and evaluate the national control programmes. The challenges currently faced by these national control programmes are the ability to maintain the reduction in morbidity achieved thus far due to the mass treatment campaigns and ensuring sustainability. For reinforcement of surveillance, the establishment of a geographical information system is suggested in order to contribute towards enhanced sustainability of these programmes. Our new working hypothesis is that targeted control accompanied by periodic mass treatment campaigns (every two to three years) can contribute to maintaining the low levels of morbidity achieved thus far. The implementation of integrated neglected tropical disease control programmes in these countries will provide means to ensure the financial sustainability of control activities for the years to come.

AIM: To study impact of once weekly iron supplementation on praziquantel cure rate, Schistosoma haematobium reinfection, and haematological parameters in pupils aged between 9 and 15 years of age in Nchelenge district, Zambia. METHODS: Pupils in the intervention group received once weekly dose of ferrous sulphate at 200 mg while those in the control received once weekly vitamin C at 100 mg for up to 9 months. Both study groups received a single dose of praziquantel at baseline. RESULTS: S haematobium reinfection intensity was significantly lower in boys in the intervention group than in boys in the control group at 6 months (P < 0.001) and 9 months (P < 0.001) of supplementation. Significantly lower S haematobium reinfection intensity was found in girls in the intervention group than in girls in the control group only at 6 months of supplementation (P = 0.018). Boys in the intervention group were 42% (Adjusted Risk Ratio = 0.58, 95% confidence interval 0.39, 0.86) less likely to be reinfected with S haematobium than in the control group at 6 months follow up. CONCLUSION: Once weekly iron supplementation can decrease S haematobium reinfection after 6 months and should be incorporated into school based schistosomiasis control programs in highly endemic areas.