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Background: Spatial modelling of STH and schistosomiasis epidemiology is now commonplace. Spatial epidemiological studies help inform decisions regarding the number of people at risk as well as the geographic areas that need to be targeted with mass drug administration; however, limited attention has been given to propagated uncertainties, their interpretation, and consequences for the mapped values. Using currently published literature on the spatial epidemiology of helminth infections we identified: (1) the main uncertainty sources, their definition and quantification and (2) how uncertainty is informative for STH programme managers and scientists working in this domain. Methodology/Principal Findings: We performed a systematic literature search using the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) protocol. We searched Web of Knowledge and PubMed using a combination of uncertainty, geographic and disease terms. A total of 73 papers fulfilled the inclusion criteria for the systematic review. Only 9% of the studies did not address any element of uncertainty, while 91% of studies quantified uncertainty in the predicted morbidity indicators and 23% of studies mapped it. In addition, 57% of the studies quantified uncertainty in the regression coefficients but only 7% incorporated it in the regression response variable (morbidity indicator). Fifty percent of the studies discussed uncertainty in the covariates but did not quantify it. Uncertainty was mostly defined as precision, and quantified using credible intervals by means of Bayesian approaches. Conclusion/Significance: None of the studies considered adequately all sources of uncertainties. We highlighted the need for uncertainty in the morbidity indicator and predictor variable to be incorporated into the modelling framework. Study design and spatial support require further attention and uncertainty associated with Earth observation data should be quantified. Finally, more attention should be given to mapping and interpreting uncertainty, since they are relevant to inform decisions regarding the number of people at risk as well as the geographic areas that need to be targeted with mass drug administration. [ABSTRACT FROM AUTHOR]

Background: Scientific literature on cystic echinococcosis (CE) reporting data on risk factors is limited and to the best of our knowledge, no global evaluation of human CE risk factors has to date been performed. This systematic review (SR) summarizes available data on statistically relevant potential risk factors (PRFs) associated with human CE. Methodology/Principal Findings: Database searches identified 1,367 papers, of which thirty-seven were eligible for inclusion. Of these, eight and twenty-nine were case-control and cross-sectional studies, respectively. Among the eligible papers, twenty-one were included in the meta-analyses. Pooled odds ratio (OR) were used as a measure of effect and separately analysed for the two study designs. PRFs derived from case-control studies that were significantly associated with higher odds of outcome were “dog free to roam” (OR 5.23; 95% CI 2.45–11.14), “feeding dogs with viscera” (OR 4.69; 95% CI 3.02–7.29), “slaughter at home” (OR 4.67; 95% CI 2.02–10.78) or at “slaughterhouses” (OR 2.7; 95% CI 1.15–6.3), “dog ownership” (OR 3.54; 95% CI 1.27–9.85), “living in rural areas” (OR 1.83; 95% CI 1.16–2.9) and “low income” (OR 1.68; 95% CI 1.02–2.76). Statistically significant PRFs from cross-sectional studies with higher odds of outcome were “age >16 years” (OR 6.08; 95% CI 4.05–9.13), “living in rural areas” (OR 2.26; 95% CI 1.41–3.61), “being female” (OR 1.38; 95% CI 1.06–1.8) and “dog ownership” (OR 1.37; 95% CI 1.01–1.86). Conclusions/Significance: Living in endemic rural areas, in which free roaming dogs have access to offal and being a dog-owner, seem to be among the most significant PRFs for acquiring this parasitic infection. Results of data analysed here may contribute to our understanding of the PRFs for CE and may potentially be useful in planning community interventions aimed at controlling CE in endemic areas. [ABSTRACT FROM AUTHOR]

Background: Human alveolar echinococcosis (AE) is a severe zoonotic disease caused by the metacestode stage of Echinococcus multilocularis. AE is commonly associated with a long incubation period that may last for more than ten years. The objective of this systematic literature review was to identify and summarize the current knowledge on statistically relevant potential risk factors (PRFs) associated with AE in humans. Methodology/Principal findings: Six bibliographic databases were searched, generating a total of 1,009 publications. Following the removal of duplicate records and the exclusion of papers that failed to meet the criteria of a previously agreed a priori protocol, 23 publications were retained; however, 6 of these did not contain data in a format that allowed their inclusion in the meta-analysis. The remaining 17 publications (6 case-control and 11 cross-sectional studies) were meta-analysed to investigate associations between AE and PRFs. Pooled odds ratio (OR) were used as a measure of effect and separately analysed for case-control and cross-sectional studies. In the case-control studies, the following PRFs for human AE showed higher odds of outcome: “dog ownership”, “cat ownership”, “have a kitchen garden”, “occupation: farmer”, “haymaking in meadows not adjacent to water”, “went to forests for vocational reasons”, “chewed grass” and “hunting / handling foxes”. In the cross-sectional studies, the following PRFs showed higher odds of outcome: “dog ownership”, “play with dogs”, “gender: female”, “age over 20 years”, “ethnic group: Tibetan”, “low income”, “source of drinking water other than well or tap”, “occupation: herding” and “low education”. Our meta-analysis confirmed that the chance of AE transmission through ingestion of food and water contaminated with E. multilocularis eggs exists, but showed also that food- and water-borne PRFs do not significantly increase the risk of infection. Conclusions/significance: This systematic review analysed international peer-reviewed articles that have over the years contributed to our current understanding of the epidemiology of human AE. The identification of potential risk factors may help researchers and decision makers improve surveillance and/or preventive measures that aim at decreasing human infection with E. multilocularis. More primary studies are needed to confirm potential risk factors and their role in the epidemiology of human AE. [ABSTRACT FROM AUTHOR]

Background: Taenia solium, a pork-borne parasitic zoonosis, is the cause of taeniasis and cysticercosis in humans. In Vietnam, poor sanitation, the practice of outdoor defecation and consumption of raw/undercooked pork have been associated with infection/exposure to T. solium in both humans and pigs. The broad-scale geographic distribution of the prevalence of T. solium varies throughout the country with infection restricted to isolated foci in the north and a more sporadic geographic distribution in the Central Highlands and the south. While cross-sectional studies have allowed the broad-scale geographic distribution of T. solium to be described, details of the geographic distribution of T. solium at finer spatial scales have not been described in detail. This study provides a descriptive spatial analysis of T. solium exposure in humans and pigs and T. solium taeniasis in humans within individual households in village communities of Dak Lak in the Central Highlands of Vietnam. Methodology/Principal findings: We used Ripley’s K-function to describe spatial dependence in T. solium exposure positive and negative human and pig households and T. solium taeniasis exposure positive and negative households in villages within the districts of Buon Don, Krong Nang and M’Drak of Dak Lak province in the Central Highlands of Vietnam. The prevalence of exposure to T. solium in pigs in Dak Lak province was 9 (95% CI 5 to 17) cases per 1000 pigs at risk. The prevalence of exposure to the parasite in humans was somewhat higher at 5 (95% CI 3 to 8) cases per 100 individuals at risk. Spatial aggregations of T. solium exposure-positive pig and human households occurred in some, but not all of the villages in the three study districts. Human exposure-positive households were found to be aggregated within a distance of 200 to 300 m in villages in Krong Nang district compared with distances of up to 1200 m in villages in M’Drak district. Although this study demonstrated the aggregation of households in which either T. solium exposure- or taeniasis-positive individuals were present, we were unable to identify an association between the two due to the very low number of T. solium taeniasis-positive households. Conclusions: Spatial aggregations of T. solium exposure-positive pig and human households occurred in some, but not all of the villages in the three study districts. We were unable to definitively identify reasons for these findings but speculate that they were due to a combination of demographic, anthropological and micro-environmental factors. To more definitively identify characteristics that increase cysticercosis risk we propose that cross-sectional studies similar in design to that described in this paper should be applied in other provinces of Vietnam. [ABSTRACT FROM AUTHOR]

Background: Individual helminth infections are ubiquitous in the tropics; geographical overlaps in endemicity and epidemiological reports suggest areas endemic for multiple helminthiases are also burdened with high prevalences of intestinal protozoan infections, malaria, tuberculosis (TB), and human immunodeficiency virus (HIV). Despite this, pathogens tend to be studied in isolation, and there remains a need for a better understanding of the community ecology and health consequences of helminth polyparasitism to inform the design of effective parasite control programs. Methodology: We performed meta-analyses to (i) evaluate the commonality of polyparasitism for helminth-helminth, helminth-intestinal protozoa, helminth-malaria, helminth-TB, and helminth-HIV co-infections, (ii) assess the potential for interspecies interactions among helminth-helminth and helminth-intestinal protozoan infections, and (iii) determine the presence and magnitude of association between specific parasite pairs. Additionally, we conducted a review of reported health consequences of multiply-infected individuals compared to singly- or not multiply-infected individuals. Principal findings: We found that helminth-helminth and helminth-intestinal protozoan multiple infections were significantly more common than single infections, while individuals with malaria, TB, and HIV were more likely to be singly-infected with these infections than co-infected with at least one helminth. Most observed species density distributions significantly differed from the expected distributions, suggesting the potential presence of interspecies interactions. All significant associations between parasite pairs were positive in direction, irrespective of the combination of pathogens. Polyparasitized individuals largely exhibited lower hemoglobin levels and higher anemia prevalence, while the differences in growth-related variables were mostly statistically insignificant. Conclusions: Our findings confirm that helminth polyparasitism and co-infection with major diseases is common in the tropics. A multitude of factors acting at various hierarchical levels, such as interspecies interactions at the within-host infra-parasite community level and environmental variables at the higher host community level, could explain the observed positive associations between pathogens; there remains a need to develop new frameworks which can consider these multilevel factors to better understand the processes structuring parasite communities to accomplish their control. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis japonica is a zoonotic parasitic disease. After nearly 70 years of control efforts in China, Schistosomiasis transmission has been reduced to a much lower level. The absence or near absence of infections in humans or livestock, based on traditional fecal and serological tests, has made the targets and priorities of future control efforts difficult to determine. However, detection of schistosome cercariae in waters using sentinel mice could be an alternative way of identifying remaining foci of infection, or even serve as a tool for evaluation of control efficacy. This method has been employed in China over last forty years. We therefore performed a meta-analysis of the relevant research to investigate if infections in sentinel mice mirror the ongoing trend of schistosomiasis transmission in China. Methods: We conducted a meta-analysis of studies reporting infection rates of S. japonicum in sentinel mice in China before Sep 1, 2018 in accordance with the PRISMA guidelines. We retrieved all relative studies based on five databases (CNKI, WanFang, VIP, PubMed and Web of Science) and the reference lists of resulting articles. For each individual study, the infection rate in sentinel mice is presented together with its 95% confidence interval (CI). Point estimates of the overall infection rates and their 95% CIs were calculated. Subgroup analyses were performed according to study periods, seasons or regions. Results: We identified 90 articles, including 290 studies covering eight endemic provinces. The overall rate in sentinel mice was 12.31% (95% CI: 10.14–14.65%) from 1980 to 2018. The value of 3.66% (95% CI: 2.62–4.85%) estimated in 2004 to 2018 was significantly lower than in 1980 to 2003 (22.96%, 95% CI: 19.25–26.89%). The estimate was significantly higher in the middle and lower reaches than in the upper reaches of the Yangtze River. The highest estimates were obtained in Hunan (30.11%, 95% CI: 25.64–34.77%) followed by Anhui (26.34%, 95% CI: 12.88–42.44%) and then Jiangxi (13.73%, 95% CI: 6.71–22.56%). Unlike the other provinces in the middle and lower reaches, no significant reduction was seen in Hubei after 2003. Even in Hubei two studies carried out after 2014 reported infections in sentinel mice, although no infected snails were reported across the province. Infections were most found in April (17.40%, 95% CI: 1.13–45.49%), July (24.98%, 95% CI: 15.64–35.62%) and October (17.08%, 95% CI 5.94–32.05%). High degrees of heterogeneity were observed. Conclusion: This meta-analysis provides a comprehensive analysis of schistosome infection in sentinel mice across China. The estimates largely mirror the ongoing trends of transmission in terms of periods and regions. Infections were most likely to occur in April, July and October. In areas where no infected snails were reported infections in sentinel mice were still observed. Due to the presence of snails and infected wildlife, detection of schistosomes in waters using such a highly sensitive method as the deployment of sentinel mice, remains of importance in schistosomiasis monitoring. We would suggest the current criteria for transmission interruption or elimination of schistosomiasis in China be adjusted by integrating the results of sentinel mice based surveys. [ABSTRACT FROM AUTHOR]

Objective: To gain further insight on the association between human toxocariasis and epilepsy in light of the new evidence in the last years. Methods: A systematic review was conducted without date and language restriction in the following electronic databases: MEDLINE (PubMed), Ingenta Connect, Science Direct (Elsevier), RefDoc, Scopus, HighWire, Scielo and the database of the Institute of Neuroepidemiology and Tropical Neurology of the Limoges University (IENT). Two investigators independently conducted the search up to November 2017. A pooled odds ratio (OR) was estimated using a random effects model. Meta-regression was conducted to investigate potential sources of heterogeneity. Results: Database search produced 204 publications. Eleven case-control studies were included that were carried out in 13 countries worldwide. A total number of 4740 subjects were considered (2159 people with epilepsy and 2581 people without epilepsy). The overall pooled OR was 1.69 (95% CI 1.42–2.01) for the association between epilepsy and Toxocara spp. seropositivity. A positive association was constantly reported in the restricted analysis (WB as confirmatory or diagnostic test, younger population, and population–based studies). Meta-regression showed no statistically significant association between covariates and outcome. Conclusion: The updated meta-analysis provides epidemiological evidence of a positive association between Toxocara seropositivity and epilepsy. New surveys supported the association, mainly population-based studies. On this basis, health strategies to reduce the impact of Toxocara spp are strongly advised. Further research should be performed to understand the physiopathological mechanisms of toxocara-associated epileptogenesis. [ABSTRACT FROM AUTHOR]

Human excreta is a low cost source of nutrients vital to plant growth, but also a source of pathogens transmissible to people and animals. We investigated the cost-savings and infection risk of soil transmitted helminths (STHs) in four scenarios where farmers used either inorganic fertilizer or fresh/composted human excreta supplemented by inorganic fertilizer to meet the nutrient requirements of rice paddies in the Red River Delta, Vietnam. Our study included two main components: 1) a risk estimate of STH infection for farmers who handle fresh excreta, determined by systematic review and meta-analysis; and 2) a cost estimate of fertilizing rice paddies, determined by nutrient assessment of excreta, a retailer survey of inorganic fertilizer costs, and a literature review to identify region-specific inputs. Our findings suggest that farmers who reuse fresh excreta are 1.24 (95% CI: 1.13–1.37, p-value<0.001) times more likely to be infected with any STH than those who do not handle excreta or who compost appropriately, and that risk varies by STH type (Ascaris lumbricoides RR = 1.17, 95% CI = 0.87–1.58, p-value = 0.29; Hookworm RR = 1.02, 95% CI = 0.50–2.06, p-value = 0.96; Trichuris trichiura RR = 1.38, 95% CI = 0.79–2.42, p-value = 0.26). Average cost-savings were highest for farmers using fresh excreta (847,000 VND) followed by those who composted for 6 months as recommended by the WHO (312,000 VND) and those who composted for a shorter time (5 months) with lime supplementation (37,000 VND/yr); however, this study did not assess healthcare costs of treating acute or chronic STH infections in the target group. Our study provides evidence that farmers in the Red River Delta are able to use a renewable and locally available resource to their economic advantage, while minimizing the risk of STH infection. [ABSTRACT FROM AUTHOR]

Lymphatic Filariasis and Onchocerciasis (river blindness) constitute pressing public health issues in tropical regions. Global elimination programs, involving mass drug administration (MDA), have been launched by the World Health Organisation. Although the drugs used are generally well tolerated, individuals who are highly co-infected with Loa loa are at risk of experiencing serious adverse events. Highly infected individuals are more likely to be found in communities with high prevalence. An understanding of the relationship between individual infection and population-level prevalence can therefore inform decisions on whether MDA can be safely administered in an endemic community. Based on Loa loa infection intensity data from individuals in Cameroon, the Republic of the Congo and the Democratic Republic of the Congo we develop a statistical model for the distribution of infection levels in communities. We then use this model to make predictive inferences regarding the proportion of individuals whose parasite count exceeds policy-relevant levels. In particular we show how to exploit the positive correlation between community-level prevalence and intensity of infection in order to predict the proportion of highly infected individuals in a community given only prevalence data from the community in question. The resulting prediction intervals are not substantially wider, and in some cases narrower, than the corresponding binomial confidence intervals obtained from data that include measurements of individual infection levels. Therefore the model developed here facilitates the estimation of the proportion of individuals highly infected with Loa loa using only estimated community level prevalence. It can be used to assess the risk of rolling out MDA in a specific community, or to guide policy decisions. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis control mainly relies on preventive chemotherapy with praziquantel (PZQ) distributed through mass drug administration. With a target of 260 million treatments yearly, reliably assessing and monitoring efficacy is all-important. Recommendations for treatment and control of schistosomiasis are supported by systematic reviews and meta-analyses of aggregated data, which however also point to limitations due to heterogeneity in trial design, analyses and reporting. Some such limitations could be corrected through access to individual participant-level data (IPD), which facilitates standardised analyses. Methodology: A systematic literature review was conducted to identify antischistosomal drug efficacy studies performed since 2000; including electronic searches of the Cochrane Infectious Diseases Group specialised register and the Cochrane Library, PubMed, CENTRAL and Embase; complemented with a manual search for articles listed in past reviews. Antischistosomal treatment studies with assessment of outcome within 60 days post-treatment were eligible. Meta-data, i.e. study-level characteristics (Schistosoma species, number of patients, drug administered, country, etc.) and efficacy parameters were extracted from published documents to evaluate the scope of an individual-level data sharing platform. Principal findings: Out of 914 documents screened, 90 studies from 26 countries were included, enrolling 20,517 participants infected with Schistosoma spp. and treated with different PZQ regimens or other drugs. Methodologies varied in terms of diagnostic approaches (number of samples and test repeats), time of outcome assessment, and outcome measure (cure rate or egg reduction rate, as an arithmetic or geometric mean), making direct comparison of published data difficult. Conclusions: This review describes the landscape of schistosomiasis clinical research. The volume of data and the methodological and reporting heterogeneity identified all indicate that there is scope for an individual participant-level database, to allow for standardised analyses. [ABSTRACT FROM AUTHOR]

Background: In the Sudan, Schistosoma mansoni infections are a major cause of morbidity in school-aged children and infection rates are associated with available clean water sources. During infection, immune responses pass through a Th1 followed by Th2 and Treg phases and patterns can relate to different stages of infection or immunity. Methodology: This retrospective study evaluated immunoepidemiological aspects in 234 individuals (range 4–85 years old) from Kassala and Khartoum states in 2011. Systemic immune profiles (cytokines and immunoglobulins) and epidemiological parameters were surveyed in n = 110 persons presenting patent S. mansoni infections (egg+), n = 63 individuals positive for S. mansoni via PCR in sera but egg negative (SmPCR+) and n = 61 people who were infection-free (Sm uninf). Immunoepidemiological findings were further investigated using two binary multivariable regression analysis. Principal Findings: Nearly all egg+ individuals had no access to latrines and over 90% obtained water via the canal stemming from the Atbara River. With regards to age, infection and an egg+ status was linked to young and adolescent groups. In terms of immunology, S. mansoni infection per se was strongly associated with increased SEA-specific IgG4 but not IgE levels. IL-6, IL-13 and IL-10 were significantly elevated in patently-infected individuals and positively correlated with egg load. In contrast, IL-2 and IL-1β were significantly lower in SmPCR+ individuals when compared to Sm uninf and egg+ groups which was further confirmed during multivariate regression analysis. Conclusions/Significance: Schistosomiasis remains an important public health problem in the Sudan with a high number of patent individuals. In addition, SmPCR diagnostics revealed another cohort of infected individuals with a unique immunological profile and provides an avenue for future studies on non-patent infection states. Future studies should investigate the downstream signalling pathways/mechanisms of IL-2 and IL-1β as potential diagnostic markers in order to distinguish patent from non-patent individuals. [ABSTRACT FROM AUTHOR]

Helminth infections affect more than a third of the world’s population. Despite very broad phylogenetic differences among helminth parasite species, a systemic Th2 host immune response is typically associated with long-term helminth infections, also known as the “helminth effect”. Many investigations have been carried out to study host gene expression profiles during helminth infections. The objective of this study is to determine if there is a common transcriptomic signature characteristic of the helminth effect across multiple helminth species and tissue types. To this end, we performed a comprehensive meta-analysis of publicly available gene expression datasets. After data processing and adjusting for study-specific effects, we identified ~700 differentially expressed genes that are changed consistently during helminth infections. Functional enrichment analyses indicate that upregulated genes are predominantly involved in various immune functions, including immunomodulation, immune signaling, inflammation, pathogen recognition and antigen presentation. Down-regulated genes are mainly involved in metabolic process, with only a few of them are involved in immune regulation. This common immune gene signature confirms previous observations and indicates that the helminth effect is robust across different parasite species as well as host tissue types. To the best of our knowledge, this study is the first comprehensive meta-analysis of host transcriptome profiles during helminth infections. [ABSTRACT FROM AUTHOR]