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Background: Soil-transmitted helminth (STH) infection is driven by a complex interaction of demographic, socioeconomic and behavioural factors, including those related to water, sanitation and hygiene (WASH). Epidemiological studies that measure both infection and potential risk factors associated with infection help to understand the drivers of transmission in a population and therefore can provide information to optimise STH control programmes. Methods: During October and November 2019, we conducted a cross-sectional survey of the prevalence and intensity of STH infection and associated risk factors among 7710 primary-school-age children from 64 primary schools across 13 districts in Dak Lak province, Vietnam. Quantitative PCR (qPCR) was used to detect and quantify STH infections. Results: The predominant STH species was the hookworm Necator americanus (overall cluster-adjusted prevalence of 13.7%), and its prevalence was heterogeneously distributed across surveyed schools (0% to 56.3%). All other STH species had a prevalence of less than 1%. Using mixed-effects logistic regression, we found that the adjusted odds ratio (aOR) was significantly higher for both infection and moderate-to-heavy-intensity infection with N. americanus among children from multiple ethnic minority groups, compared to children from the majority group (Kinh). Adjusted odds of infection with N. americanus were also higher in children who reported practising open defecation at school (aOR 1.42, 95% CI 1.05, 1.93, P = 0.02) and in those who had an unimproved household water supply (aOR 1.28, 95% CI 1.04, 1.57, P = 0.02). Conversely, children with a flushing household toilet had a reduced risk of infection (aOR 0.58, 95% CI 0.47, 0.70, P < 0.01), as did those whose primary female carer attended secondary (aOR 0.65, 95% CI 0.51, 0.84, P < 0.01) or tertiary education (aOR 0.39, 95% CI 0.24, 0.63, P < 0.01). Conclusions: This study is the largest reported prevalence survey of STH infec

Background: Soil-transmitted helminth (STH) infection control programs typically consist of school-based preventive chemotherapy (PC) targeted to school-aged children. STH reservoirs in untreated community members contribute to ongoing transmission in children. The CoDe-STH (Community Deworming against STH) trial, conducted in Dak Lak province, Vietnam, between October 2019 and November 2020, aimed to determine whether community-wide mass drug administration (MDA) is more effective than school-based targeted PC in reducing STH prevalence and intensity in children. Methods: In this two-arm cluster randomised controlled trial, 64 primary schools were randomly assigned 1:1 to receive either school-based targeted PC (“school arm”) or community-wide MDA (“community arm”). A single dose of albendazole 400 mg was used for deworming. The primary outcome was hookworm prevalence in schoolchildren, measured using quantitative real-time PCR. We also measured infection intensity for Necator americanus only, using qPCR cycle threshold (Ct) values converted into eggs per gram of faeces (EPG). Analysis was by intention to treat. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619000309189). Findings: The analysis included 4955 children in the school arm and 5093 children in the community arm. N. americanus was the dominant STH species. The relative reduction in hookworm prevalence was not significantly different between the school arm (30.1%, 95% confidence interval [CI] 20.5–36.9) and the community arm (34.6%, 95% CI 19.9–49.4). Due to lower baseline prevalence than expected, the study was underpowered to detect a difference in prevalence reduction between the study arms. The community arm showed significantly greater relative reduction in N. americanus infection intensity (56.0%, 95% CI 39.9–72.1) compared to the school arm (3.4%, 95% CI −24.7 to 31.4). The community arm also show

BACKGROUND: Reliable and detailed data on the prevalence of tuberculosis (TB) with sub-national estimates are scarce in Ethiopia. We address this knowledge gap by spatially predicting the national, sub-national and local prevalence of TB, and identifying drivers of TB prevalence across the country. METHODS: TB prevalence data were obtained from the Ethiopia national TB prevalence survey and from a comprehensive review of published reports. Geospatial covariates were obtained from publicly available sources. A random effects meta-analysis was used to estimate a pooled prevalence of TB at the national level, and model-based geostatistics were used to estimate the spatial variation of TB prevalence at sub-national and local levels. Within the MBG Plugin Framework, a logistic regression model was fitted to TB prevalence data using both fixed covariate effects and spatial random effects to identify drivers of TB and to predict the prevalence of TB. RESULTS: The overall pooled prevalence of TB in Ethiopia was 0.19% [95% confidence intervals (CI): 0.12%-0.28%]. There was a high degree of heterogeneity in the prevalence of TB (I2 96.4%, P <0.001), which varied by geographical locations, data collection periods and diagnostic methods. The highest prevalence of TB was observed in Dire Dawa (0.96%), Gambela (0.88%), Somali (0.42%), Addis Ababa (0.28%) and Afar (0.24%) regions. Nationally, there was a decline in TB prevalence from 0.18% in 2001 to 0.04% in 2009. However, prevalence increased back to 0.29% in 2014. Substantial spatial variation of TB prevalence was observed at a regional level, with a higher prevalence observed in the border regions, and at a local level within regions. The spatial distribution of TB prevalence was positively associated with population density. CONCLUSION: The results of this study showed that TB prevalence varied substantially at sub-national and local levels in Ethiopia. Spatial patterns were associated with population density. These results s

The study aimed to explore sociocultural factors influencing the risk of malaria and practices and beliefs towards malaria prevention, transmission and treatment in a remote village in Khatyad Rural Municipality (KRM) of Nepal. A sequential exploratory mixed methods approach was used. Qualitative data were collected through 25 one-on-one, in-depth interviews followed by a face-to-face household survey (n = 218) among people from a village in KRM believed to have a high risk of malaria. Traditional practices such as Chhaupadi requiring the seclusion of women during menstruation and post-partum, transhumance, and reliance on traditional healers for the management of malaria were common practices in the village. The household survey found 98.1% of women faced menstrual exile either inside the house or in a separate hut, with 64.2% not having access to Long-lasting Insecticidal Nets (LLINs). Hardships and economic constraints compelled villagers to migrate seasonally for work to malaria-endemic areas in India, thereby exposing themselves to the risk of malaria. Persistent traditional beliefs and seasonal migration could threaten the elimination goals set by the national malaria program.

engue is an arthropod-borne disease caused by one or more of the four dengue viruses (DENV1–4), which belong to the genus Flavivirus and family Flaviviridae.

Member countries of the Asia Pacific Malaria Elimination Network are pursuing the regional goal of malaria elimination by 2030. The countries are in different phases of malaria elimination, but most have demonstrated success in shrinking the malaria map in the region. However, continued transmission in hard-to-reach populations, including border and forest malaria, remains an important challenge. In this article, we review strategies for improving intervention coverage in hard-to-reach populations. Currently available preventive measures, including long-lasting insecticidal nets and long-lasting insecticidal hammocks, and prompt diagnosis and treatment need to be expanded to hard-to-reach populations. This can be done through mobile malaria clinics, village volunteer malaria workers and screening posts. Malaria surveillance in the hard-to-reach areas can be enhanced through tools such as spatial decision support systems. Policy changes by the malaria programs will be required for implementing the strategies outlined in this article. However, strategies or tools may be suitable for some population groups but difficult to implement in other groups.

Background: Infectious diseases such as tuberculosis (TB), malaria and soil-transmitted helminthiasis continue to impose a significant global health burden and socio-economic impact. Globally, minority indigenous people are disproportionately affected by poverty and are shown to experience a disparate burden of disease and poorer health outcomes than the comparative majority population. Despite these inequalities, countries rarely systematically compile epidemiological data disaggregated by ethnicity to enable the extent of the differential to be quantified. Methods: The systematic review will be reported in accordance with The Preferred Reporting Items for Systematic Review and Meta- Analyses (PRISMA) guidelines. Systematic searches will be conducted in EMBASE, Medline, Scopus and Web of Science for studies reporting data which enable the prevalence of TB, malaria, and/or soil-transmitted helminth (STH) infections amongst minority indigenous populations within the Southeast Asia Region (SEAR) and Western Pacific Region (WPR) to be calculated. Where studies provide data on disease prevalence for both minority indigenous and other populations within the same study, a comparative analysis will be undertaken. In addition to a narrative synthesis, where sufficient data are available, a random-effects meta-analysis will be conducted to obtain a pooled estimate value for each disease/infection by country and mortality stratum. Heterogeneity between studies will be examined using the Cochran’s Q test and quantitatively measured by the index of heterogeneity squared (I2) statistics. The methodological quality of the included studies will be assessed using a modified Newcastle-Ottawa Scale. Discussion: This systematic review aims to analyse the available data on the prevalence of TB, malaria and STH infections within minority indigenous populations of the SEAR and WPR. Registration: Open Science Framework registration: osf.io/m6sqc

Tuberculosis (TB) is the leading cause of death from a bacterial pathogen worldwide. China has the third highest TB burden in the world, with a high reported burden in Hunan Province (amongst others). This study aimed to investigate the spatial distribution of TB and identify socioeconomic, demographic, and environmental drivers in Hunan Province, China. Numbers of reported cases of TB were obtained from the Tuberculosis Control Institute of Hunan Province, China. A wide range of covariates were collected from different sources, including from the Worldclim database, and the Hunan Bureau of Statistics. These variables were summarized at the county level and linked with TB notification data. Spatial clustering of TB was explored using Moran’s I statistic and the Getis–Ord statistic. Poisson regression models were developed with a conditional autoregressive (CAR) prior structure, and with posterior parameters estimated using a Bayesian approach with Markov chain Monte Carlo (MCMC) simulation. A total of 323,340 TB cases were reported to the Hunan TB Control Institute from 2013 to 2018. The mean age of patients was 51.7 years (SD + 17.6 years). The majority of the patients were male (72.6%, n = 234,682) and had pulmonary TB (97.5%, n = 315,350). Of 319,825 TB patients with registered treatment outcomes, 306,107 (95.7%) patients had a successful treatment outcome. The annual incidence of TB decreased over time from 85.5 per 100,000 population in 2013 to 76.9 per 100,000 population in 2018. TB case numbers have shown seasonal variation, with the highest number of cases reported during the end of spring and the beginning of summer. Spatial clustering of TB incidence was observed at the county level, with hotspot areas detected in the west part of Hunan Province. The spatial clustering of TB incidence was significantly associated with low sunshine exposure (RR: 0.86; 95% CrI: 0.74, 0.96) and a low prevalence of contraceptive use (RR: 0.88; 95% CrI: 0.79, 0.98). Substantial

Community engagement (CE) is important for malaria prevention, control and ultimately elimination. As the decline of malaria has plateaued over the last 5 years, strengthening CE approaches will be necessary to enhance health promotion practice and policy to drive malaria transmission down further. Countries have adopted a wide range of public health intervention approaches for malaria prevention and control that best suit their context. This review will examine the existing evidence on the various CE approaches adopted by malaria programmes across the world and their outcomes. Methodology and analysis The review methodology will follow the updated Joanna Briggs Institute guide for scoping review, 2017, which is based on the framework developed by Arksey and O'Malley and further developed by Levac Colquhoun and O'Brien. Proquest, Web of Knowledge and Medline will be searched for publications from January 2000 to 31 March 2021 while Google search engine will be used to find any grey literature. The eligibility criteria will be as follows: review will include primary studies written in the English language using appropriate study designs and methods, including quantitative, qualitative and mixed methods designs; and case, programme or project reports. Information on CE approaches designed specifically for malaria prevention, control, elimination and their outcomes will be explored. Subheadings and free text terms for € community engagement' and € malaria' will be used for the search. The article screening and data extraction will be examined by two reviewers after the initial search, and any disputes will be resolved by a third reviewer through discussion. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews guide will be used to present the review methods and the results from the search. The scoping review results will identify and map the available evidences, sources of information and research gaps in the area of CE a

District Health Information Systems 2 (DHIS2) is used for supporting health information management in 67 countries, including Solomon Islands. However, there have been few published evaluations of the performance of DHIS2-enhanced disease reporting systems, in particular for monitoring infectious diseases such as malaria. The aim of this study was to evaluate DHIS2 supported malaria reporting in Solomon Islands and to develop recommendations for improving the system.

BACKGROUND: The emergence and re-emergence of scrub typhus has been reported in the past decade in many global regions. In this study, we aim to identify potential scrub typhus infection risk zones with high spatial resolution in Qingdao city, in which scrub typhus is endemic, to guide local prevention and control strategies. METHODOLOGY/PRINCIPAL FINDINGS: Scrub typhus cases in Qingdao city during 2006-2018 were retrieved from the Chinese National Infectious Diseases Reporting System. We divided Qingdao city into 1,101 gridded squares and classified them into two categories: areas with and without recorded scrub typhus cases. A boosted regression tree model was used to explore environmental and socioeconomic covariates associated with scrub typhus occurrence and predict the risk of scrub typhus infection across the whole area of Qingdao city. A total of 989 scrub typhus cases were reported in Qingdao from 2006-2018, with most cases located in rural and suburban areas. The predicted risk map generated by the boosted regression tree models indicated that the highest infection risk areas were mainly concentrated in the mid-east and northeast regions of Qingdao, with gross domestic product (20.9%±1.8% standard error) and annual cumulative precipitation (20.3%±1.1%) contributing the most to the variation in the models. By using a threshold environmental suitability value of 0.26, we identified 757 squares (68.7% of the total) with a favourable environment for scrub typhus infection; 66.2% (501/757) of the squares had not yet recorded cases. It is estimated that 6.32 million people (72.5% of the total population) reside in areas with a high risk of scrub typhus infection. CONCLUSIONS/SIGNIFICANCE: Many locations in Qingdao city with no recorded scrub typhus cases were identified as being at risk for scrub typhus occurrence. In these at-risk areas, awareness and capacity for case diagnosis and treatment should be enhanced in the local medical service institutes.

Scrub typhus is a life-threatening vector-borne disease. During the past decade, the number of areas affected by this disease has expanded in many countries. In this study, we aim to identify the spatiotemporal and demographic characteristics of scrub typhus in Southwest China, an emerging endemic region for scrub typhus. Population-based surveillance data capturing scrub typhus cases in two provinces of Southwest China during 2006–2017 were retrieved. Descriptive temporal and spatial analyses were conducted and stratified by age group. The space-time scan statistic was used to identify spatiotemporal clusters of scrub typhus occurrence at the county level. During the study period, 30,001 scrub typhus cases were recorded in Southwest China, with a total of 61.0% (191/313) of counties being affected; most cases (94.3%) occurred in rural areas. The annual incidence rate increased substantially from 0.25/100,000 in 2006 to 5.38/100,000 in 2017 (>21-fold change). The 0- to 4-year-old and 45- to 64-year-old subgroups had the highest cumulative incidence rates (57.46 and 32.98/100,000, respectively). Furthermore, since 2006, the 0- to 4-year-old (slope = 0.83, p <.01) and 45–64-year-old (slope = 0.69, p <.01) age groups have had the highest increases in incidence of all age groups. The most likely spatial cluster of overall cases (relative risk = 4.13, p <.01) occurred in the southern region of Southwest China and included 41 high-risk counties. In conclusion, scrub typhus appears to be widely distributed and rapidly increasing in Southwest China. Young children and middle-aged adults were the most severely affected groups, and the disease appeared to predominantly cluster in the southern part of Southwest China. Further in-depth surveys to determine the epidemiological characteristics and driving factors of this emerging disease and to facilitate effective control programmes among high-risk groups in the affected areas should be promoted.

Throughout history, pandemics of viral infections such as HIV, Ebola and Influenza have disrupted health care systems, including the prevention and control of endemic diseases. Such disruption has resulted in an increased burden of endemic diseases in post-pandemic periods. The current coronavirus disease 2019 (COVID-19) pandemic could cause severe dysfunction in the prevention and control of tuberculosis (TB), the infectious disease that causes more deaths than any other, particularly in low- and middle-income countries where the burden of TB is high. The economic and health crisis created by the COVID-19 pandemic as well as the public health measures currently taken to stop the spread of the virus may have an impact on household TB transmission, treatment and diagnostic services, and TB prevention and control programs. Here, we provide an overview of the potential impact of COVID-19 on TB programs and disease burden, as well as possible strategies that could help to mitigate the impact.

Introduction Tuberculosis (TB), a major public health concern in Ethiopia, is distributed heterogeneously across the country. Mapping TB prevalence at national and subnational levels can provide information for designing and implementing control strategies. Data for spatial analysis can be obtained through systematic review of the literature, and spatial prediction can be done by meta-analysis of published data (geospatial meta-analysis). Geospatial meta-analysis can increase the power of spatial analytic models by making use of all available data. It can also provide a means for spatial prediction where new survey data in a given area are sparse or not available. In this report, we present a protocol for a geospatial meta-analysis to investigate the spatial patterns of TB prevalence in Ethiopia. Methods and analysis To conduct this study, a national TB prevalence survey, supplemented with data from a systematic review of published reports, will be used as the source of TB prevalence data. Systematic searching will be conducted in PubMed, Scopus and Web of Science for studies published up to 15 April 2020 to identify all potential publications reporting TB prevalence in Ethiopia. Data for covariates for multivariable analysis will be obtained from different, readily available sources. Extracted TB survey and covariate data will be georeferenced to specific locations or the centroids of small administrative areas. A binomial logistic regression model will be fitted to TB prevalence data using both fixed covariate effects and random geostatistical effects based on the approach of model-based geostatistics. Markov Chain Monte Carlo simulation will be conducted to obtained posterior parameter estimations, including spatially predicted prevalence. Ethics and dissemination Ethical approval will not be required for this study as it will be based on deidentified, aggregate published data. The final report of this review will be disseminated through publication in a peer-rev

The transmission soil transmitted helminths (STH) occurs via ingestion of or contact with infective stages present in soil contaminated with human faeces. It follows therefore that efforts to reduce faecal contamination of the environment should help to reduce risk of parasite exposure and improvements in water, sanitation and hygiene (WASH) are seen as essential for the long-term, sustainable control of STH. However, the link between WASH and STH is not always supported by the available evidence from randomised controlled trials, which report mixed effects of WASH intervention on infection risk. This review critically summarises the available trial evidence and offers an interpretation of the observed heterogeneity in findings. The review also discusses the implications of findings for control programmes and highlights three main issues which merit further consideration: intervention design, exposure assessment, and intervention fidelity assessment.

Background: Influenza and pneumococcal vaccine uptake in the older population aged 65 years or over of Hong Kong dramatically increased since the 2003 SARS outbreak. This study is aimed to evaluate the impact of increased coverage of influenza and pneumococcal vaccines by comparing the change of disease burden in the older population of Hong Kong, with the burden in the older population of Brisbane with relatively high vaccine coverage in the past fifteen years. Methods: Time series segmented regression models were applied to weekly numbers of cause-specific mortality or hospitalization of Hong Kong and Brisbane. Annual excess rates of mortality or hospitalization associated with influenza in the older population were estimated for the pre-SARS (reference period), post-SARS and post-pandemic period, respectively. The rate ratios (RRs) between these periods were also calculated to assess the relative change of disease burden. Results: Compared to the pre-SARS period, excess rates of mortality associated with influenza during the post-SARS period in Hong Kong decreased for cardiorespiratory diseases (RR = 0.90, 95% CI 0.80, 1.01), stroke (RR = 0.74, 95% CI 0.50, 1.09), and ischemic heart diseases (RR = 0.45, 95% CI 0.34, 0.58). The corresponding RRs in Brisbane were 0.79 (95% CI 0.54, 1.15), 0.33 (0.13, 0.80), and 1.09 (0.62, 1.90), respectively. Only the mortality of ischemic heart diseases showed a greater reduction in Hong Kong than in Brisbane. During the post-pandemic period, excess rates of all-cause mortality increased in Hong Kong, but to a lesser extent than in Brisbane (RR = 1.41 vs 2.39). Conclusion: A relative decrease (or less of an increase) of influenza disease burden was observed in the older population of Hong Kong after increased coverage of influenza and pneumococcal vaccines in this population, as compared to those of Brisbane where vaccination rates remained stable. The lack of sig

Objectives. This research study aims to conduct a systematic review and critical appraisal of the quality of the existing peer-reviewed journal literature looking into the economic evaluation of control strategies used in parasitic diseases (i.e., STH and schistosomiasis). Methods. Database searches were conducted in Embase, Science Direct, Medline, CINAHL, Econ Lit, and Academic Search Elite, by using search keywords or phrases. Using the predefined inclusion and exclusion criteria, a review of published online articles between January 1990 and December 2012 was conducted. Aside from the set of good practice guidelines in conducting economic evaluations, assessment of the quality of economic evaluations was also carried out following the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Results. Given the inclusion and exclusion criteria set by this review, we systematically reviewed thirteen shortlisted samples of economic analysis studies. The current systematic review shows a wide variety of methodological approaches across studies, including differences in the type of economic evaluation, perspective, time horizon, approach, and adjustments for timing and certainty used. Conclusions. In general, the economic evaluation studies that have been examined in this review have complied with the set of criteria of good practice in conducting an economic evaluation and that it can be considered helpful in making decisions and in understanding the economics of controlling these parasitic diseases.

Health security is here defined as the avoidance and containment of infectious disease threats with the potential to cause social and economic harms on a national, regional or global scale (1). It is a regional and global public good that provides benefit to all members of society and is central to the achievement of many of the Sustainable Development Goals (SDGs). Health security goes beyond the domain of human public health: animal health is integral to health security, given that the majority of emerging diseases in humans are of animal origin (i.e. zoonoses), and transboundary animal diseases pose a threat to food security.

Background: Current guidelines and targets for soil-transmitted helminth (STH) control focus on school-based deworming for school-age children, given the high risk of associated morbidity in this age group. However, expanding deworming to all age groups may achieve improved STH control among both the community in general and school-age children, by reducing their risk of reinfection. This trial aims to compare school-based targeted deworming with community-wide mass deworming in terms of impact on STH infections among school-age children. Methods: The CoDe-STH (Community Deworming against STH) trial is a cluster-randomised controlled trial (RCT) in 64 primary schools in Dak Lak province, Vietnam. The control arm will receive one round of school-based targeted deworming with albendazole, while in the intervention arm, community-wide mass deworming with albendazole will be implemented alongside school-based deworming. Prevalence of STH infections will be measured in school-age children at baseline and 12 months following deworming. The primary outcome is hookworm prevalence in school-age children at 12 months, by quantitative PCR. Analysis will be intention-to-treat, with outcomes compared between study arms using generalised linear and non-linear mixed models. Additionally, cost-effectiveness of mass and targeted deworming will be calculated and compared, and focus group discussions and interviews will be used to assess acceptability and feasibility of deworming approaches. Individual based stochastic models will be used to predict the impact of mass and targeted deworming strategies beyond the RCT timeframe to assess the likelihood of parasite population 'bounce-back' if deworming is ceased due to low STH prevalence. Discussion: The first large-scale trial comparing mass and targeted deworming for STH control in South East Asia will provide key information for policy makers regarding the optimal design of STH control programs. Trial registration: ACTRN12619000309189

Background: Giardiasis is a common diarrhoeal disease caused by the protozoan Giardia duodenalis. It is prevalent in low-income countries in the context of inadequate access to water, sanitation and hygiene (WASH), and is frequently co-endemic with neglected tropical diseases such as soil-transmitted helminth (STH) infections. Large-scale periodic deworming programmes are often implemented in these settings; however, there is limited evidence for the impact of regular anthelminthic treatment on G. duodenalis infection. Additionally, few studies have examined the impact of WASH interventions on G. duodenalis.

Background Soil-transmitted helminth (STH) infections remain highly endemic across the Philippines, and are believed to be important contributors to delayed cognitive development of school-aged children. Identification of communities where children are at risk of functional illiteracy is important for the attainment of Sustainable Development Goals target for literacy. We aimed to quantify the associations between the spatial variation of STH infections and functional literacy indicators adjusting for other important contributors, and identify priority areas in the Philippines in need of interventions. Methodology/Principal findings We used data from 11,313 school-aged children on functional literacy indicators collected in 2008. Nested fixed-effects multinomial regression models were built to determine associations between STH endemicity and geographical distribution of functional literacy, adjusting for demographics, household level variables, and the prevalence of malaria. Bayesian multinomial geostatistical models were built to geographically predict the prevalence of each level of functional literacy. The number of school-aged children belonging to each of the functional literacy indicator classes was forecast for 2017. We estimated 4.20% of functional illiteracy burden among school-aged children in Mindanao might be averted by preventing T. trichiura infections. Areas predicted with the highest prevalence of functional illiteracy were observed in localised areas of the eastern region of the Visayas, and the south-eastern portion of Mindanao. Conclusions/Significance The study demonstrates significant geographical variation in burden of functional illiteracy in school-aged children associated with STH infections suggesting that targeted helminth control could potentially promote the development of cognitive function of school-aged children in the Philippines. The benefits of a spatially targeted strategy should be tested by future studies.

Background: Acute undifferentiated febrile illness (AUFI) is caused by a multitude of diverse pathogens, with significant morbidity and mortality in the developing world. The objective of this review was to characterise the diversity and relative importance of common infectious aetiologies of AUFI in South and Southeast Asia. Methods: We conducted a comprehensive literature review to identify common aetiologies of AUFI in Asian countries. Four medical and life sciences databases including PubMed, Medline, Embase and Cochrane Central, and Google Scholar were searched for articles published from January 1998 to March 2019. Results: Forty-three studies met the inclusion criteria. Among AUFI cases, viral aetiologies at 18.5% (14888) were more common than bacterial aetiologies (12.9% [10384]). From 80,554 cases, dengue fever was the most common aetiology (11.8%, 9511), followed by leptospirosis (4.4%, 3549), typhoid (4.0%, 3258), scrub typhus (4.0%, 3243) and influenza other than H1N1 (3.1%, 2514). In both adults and children: dengue fever was the leading cause of AUFI with 16.6% (1928) and 18.7% (1281) of the total cases. In admitted patients, dengue fever was the main cause of AUFI at 16.4% (2377), however leptospirosis at 13.9% (2090) was the main cause of AUFI for outpatients. In South Asia, dengue fever was the main cause of AUFI, causing 12.0% (6821) of cases, whereas in Southeast Asia, leptospirosis was the main diagnosis, causing 12.1% (2861) of cases. Conclusions: In this study the most common causes of AUFI were viral, followed by bacterial and protozoal (malaria) infections. Dengue was the commonest virus that caused AUFI while leptospirosis and typhoid were important bacterial infectious causes. Therefore, it is imperative to maintain a sound epidemiological knowledge of AUFI so that evidence-based diagnostic criteria and treatment guidelines can be developed.

Objectives: To describe and quantify spatiotemporal trends of dengue fever at district level in Sumatra and Kalimantan, Indonesia in relation to forest cover and climatic factors.

Water, sanitation and hygiene interventions have been advocated as important complements to deworming programs to improve soil-transmitted helminth control. Evidence for the impact of water, sanitation and hygiene on soil-transmitted helminth infections is mixed, and based mainly on cross-sectional studies. In this study, we assessed associations between individual- and household-level water, sanitation and hygiene variables and soil-transmitted helminth infections, using data collected during the 2 year follow-up study period of the WASH for WORMS randomised controlled trial in Timor-Leste. Data were collected across four surveys, conducted at 6 monthly intervals in 23 communities. We analysed water, sanitation and hygiene and sociodemographic variables as risk factors for infection with Necator americanus, Ascaris spp., and undifferentiated soil-transmitted helminth infection, using generalised linear mixed models to account for clustering at community, household and participant levels. Water, sanitation and hygiene risk factors were examined both concurrently and with a 6 month lag period that coincided with the most recent deworming. The analysis included 2333 participants. Factors associated with N. americanus infection included age group, male sex (adjusted odds ratio (aOR) 3.1, 95% confidence interval (CI) 2.4–4.2), working as a farmer (aOR 1.7, 95% CI 1.2–2.4), and completing secondary school or higher (aOR 0.29, 95% CI 0.16–0.53). Risk factors for Ascaris spp. infection included age group, living in a dwelling with more than six people (aOR 1.6, 95% CI 1.1–2.3), having a tube well or borehole as the household water source (aOR 3.7, 95% CI 1.3–10.8), and using a latrine shared between households 6 months previously (aOR 2.3, 95% CI 1.2–4.3). Handwashing before eating was protective against infection with any soil-transmitted helminth (aOR 0.79, 95% CI 0.65–0.95). In the context of regular deworming, few water, sanitation and hygiene-related factors were asso

Water, sanitation, and hygiene (WASH) interventions have been proposed as an important complement to deworming programs for sustainable control of soil-transmitted helminth (STH) infections. We aimed to determine whether a community-based WASH program had additional benefits in reducing STH infections compared with community deworming alone. We conducted the WASH for WORMS cluster-randomized controlled trial in 18 rural communities in Timor-Leste. Intervention communities received a WASH intervention that provided access to an improved water source, promoted improved household sanitation, and encouraged handwashing with soap. All eligible community members in intervention and control arms received albendazole every 6 months for 2 years. The primary outcomes were infection with each STH, measured using multiplex real-time quantitative polymerase chain reaction. We compared outcomes between study arms using generalized linear mixed models, accounting for clustering at community, household, and individual levels. At study completion, the integrated WASH and deworming intervention did not have an effect on infection with Ascaris spp. (relative risk [RR] 2.87, 95% confidence interval [CI]: 0.66–12.48, P = 0.159) or Necator americanus (RR 0.99, 95% CI: 0.52–1.89, P = 0.987), compared with deworming alone. At the last follow-up, open defecation was practiced by 66.1% (95% CI: 54.2–80.2) of respondents in the control arm versus 40.2% (95% CI: 25.3–52.6) of respondents in the intervention arm (P = 0.005). We found no evidence that the WASH intervention resulted in additional reductions in STH infections beyond that achieved with deworming alone over the 2-year trial period. The role of WASH on STH infections over a longer period of time and in the absence of deworming remains to be determined.

Functional literacy is one of the targets of the Sustainable Development Goals (SDGs) of the United Nations. Functional literacy indicators are likely to vary between locations given the geographical variability of its major determinants. This property poses a challenge to decisions around efficient allocation of population services and resources to mitigate the impact of functional literacy in populations most in need. Using functional literacy indicators of 11,313 school-aged children collected in 2008 during the nationwide survey, the current study examined the association between functional literacy and geographical disparities in socioeconomic status (SES), water supply, sanitation and hygiene, household education stimuli, and environmental variables in all three regions of the Philippines (Luzon, the Visayas, and Mindanao). Three nested fixed-effects multinomial regression models were built to determine associations between functional literacy and a wide array of variables. Our results showed the general prevalence rate of functional illiteracy as being 4.7%, with the highest prevalence rate in the Visayas, followed by Mindanao and Luzon (7.5%, 6.9%, and 3.0%, respectively. Our results indicated that in Luzon prevalence of functional illiteracy was explained by variation in household education stimuli scores, sources of drinking water, and type of toilet facility. In Mindanao and the Visayas prevalence of functional illiteracy was primarily explained by geographical variation in SES, and natural environmental conditions. Our study highlights region-specific determinants of functional literacy and the need for geographically targeted, integrated interventions. View Full-Text

Background: Periodic mass distribution of benzimidazole anthelminthic drugs is the key strategy to control soil-transmitted helminths (STH) globally. However, benzimidazoles have low efficacy against Trichuris trichiura, and there are concerns about benzimidazole resistance potentially emerging in humans. Therefore, identifying alternative drug regimens is a pressing priority. We present a systematic review and network meta-analysis, comparing the efficacy of 21 different anthelminthic drug regimens, including standard, novel, and combination treatments. Methods: We searched PubMed, MEDLINE, Embase, Web of Science, and Cochrane databases and identified studies comparing anthelminthic treatments to each other or placebo. The outcomes calculated were relative risk (RR) of cure and difference in egg reduction rates (dERR). We used an automated generalized pair-wise modelling framework to generate mixed treatment effects against a common comparator, the current standard treatment (single-dose albendazole). This study is registered with PROSPERO (CRD42016050739). Findings: Our search identified 4876 studies, of which 114 were included in meta-analysis. Results identified several drug combinations with higher efficacy than single-dose albendazole for T. trichiura, including albendazole-ivermectin (RR of cure 3.22, 95%CI 1.84–5.63; dERR 0.97, 95%CI 0.21–1.74), albendazole-oxantel pamoate (RR 5.07, 95%CI 1.65–15.59; dERR 0.51, 95%CI 0.450–0.52), mebendazole-ivermectin (RR 3.37, 95%CI 2.20–5.16), and tribendimidine-oxantel pamoate (RR 4.06, 95%CI 1.30–12.64). Interpretation: There are several promising drug combinations that may enhance the impact of STH control programs on T. trichiura, without compromising efficacy against A. lumbricoides and hookworm. We suggest further, large-scale trials of these drug combinations and consideration of their use in STH control programs where T. trichiura is present.

Clostridium difficile infections (CDIs) affect patients in hospitals and in the community, but the relative importance of transmission in each setting is unknown. We developed a mathematical model of C. difficile transmission in a hospital and surrounding community that included infants, adults, and transmission from animal reservoirs. We assessed the role of these transmission routes in maintaining disease and evaluated the recommended classification system for hospital and community-acquired CDIs.

Background: Influenza and pneumococcal vaccine uptake in the older population aged 65 years or over of Hong Kong dramatically increased since the 2003 SARS outbreak. This study is aimed to evaluate the impact of increased coverage of influenza and pneumococcal vaccines by comparing the change of disease burden in the older population of Hong Kong, with the burden in the older population of Brisbane with relatively high vaccine coverage in the past fifteen years. Methods: Time series segmented regression models were applied to weekly numbers of cause-specific mortality or hospitalization of Hong Kong and Brisbane. Annual excess rates of mortality or hospitalization associated with influenza in the older population were estimated for the pre-SARS (reference period), post-SARS and post-pandemic period, respectively. The rate ratios (RRs) between these periods were also calculated to assess the relative change of disease burden. Results: Compared to the pre-SARS period, excess rates of mortality associated with influenza during the post-SARS period in Hong Kong decreased for cardiorespiratory diseases (RR = 0.90, 95% CI 0.80, 1.01), stroke (RR = 0.74, 95% CI 0.50, 1.09), and ischemic heart diseases (RR = 0.45, 95% CI 0.34, 0.58). The corresponding RRs in Brisbane were 0.79 (95% CI 0.54, 1.15), 0.33 (0.13, 0.80), and 1.09 (0.62, 1.90), respectively. Only the mortality of ischemic heart diseases showed a greater reduction in Hong Kong than in Brisbane. During the post-pandemic period, excess rates of all-cause mortality increased in Hong Kong, but to a lesser extent than in Brisbane (RR = 1.41 vs 2.39). Conclusion: A relative decrease (or less of an increase) of influenza disease burden was observed in the older population of Hong Kong after increased coverage of influenza and pneumococcal vaccines in this population, as compared to those of Brisbane where vaccination rates remained stable. The lack of significant findings in some disease categories highlights the challen

The transmission soil transmitted helminths (STH) occurs via ingestion of or contact with infective stages present in soil contaminated with human faeces. It follows therefore that efforts to reduce faecal contamination of the environment should help to reduce risk of parasite exposure and improvements in water, sanitation and hygiene (WASH) are seen as essential for the long-term, sustainable control of STH. However, the link between WASH and STH is not always supported by the available evidence from randomised controlled trials, which report mixed effects of WASH intervention on infection risk. This review critically summarises the available trial evidence and offers an interpretation of the observed heterogeneity in findings. The review also discusses the implications of findings for control programmes and highlights three main issues which merit further consideration: intervention design, exposure assessment, and intervention fidelity assessment.

Avian Influenza (AI) is a viral disease that affects birds and humans. Several AI lineages infect humans and there is potential for lineages to cause human pandemics. New developments in AI have occurred in recent years: several novel zoonotic strains (e.g. H7N9, H5N6, H10N8) emerged in China, and North America experienced mass outbreaks of novel lineages in commercial poultry. This presented an opportunity to study emerging strains at a time when there was greatest uncertainty about the nature of these viruses and how they would behave. This PhD aimed to use and compare novel epidemiologic, modelling, geospatial and computational methods to uncover epidemiological insights, particularly to evaluate risk and patterns of spread of novel viruses. In chapters 2 and 4, publically available information was used to describe trends and patterns of recently emerged zoonotic AIs in comparison to historical occurrences of zoonotic AI, and to quantitatively characterise the prevalence of two potentially pandemic strains (H5N1 and H7N9) in avian populations through a meta-analysis. In chapters 3, 5 and 6, spatial data was used to identify locations of highest disease incidence, predict areas at risk of disease incursions, and identify factors driving disease spread. Chapter 3 used a spatial overlaying approach to show spatial dynamics of H5 clade 2.3.4.4 viruses in North America appeared were more consistent with domestic poultry distribution compared to migratory flyways. Chapter 5 combined a machine learning algorithm with a spatial risk framework to identify specific areas at risk of H5N1 and H7N9 transmission. In Chapter 6, H5N1 and H7N9 spread was modelled using a Bayesian phylogeography approach, and factors contributing to disease spread were identified. There is a vastly growing amount of digital data sources and computational tools now available to the desktop epidemiologist. This thesis provides examples of how these can be used; the final chapter discusses their bene

Background Clostridium difficile infection is a serious hospital-acquired infection, causing negative outcomes for those who are afflicted by it. Hospital length of stay is known to be a risk factor for transmission and significant reductions in infection numbers can be realised if transmission is reduced. Methods A Markov model was constructed to compare the impact that five alternative healthcare scenarios had on total C. difficile infections, QALYs gained and total number of patients requiring treatment in ICU. A previously published stochastic transmission model for C. difficile informed scenario effectiveness, while other parameters were estimated from published literature, administrative datasets and expert opinion. Results Reducing inpatient LOS disrupts transmission of C. difficile and results in a large reduction of total infections. In turn, an increase in QALYs is expected when the number of infections is reduced. A reduction in infections reduces the number of ICU admissions, which is likely to have a large economic benefit in the Australian setting. Coupling a reduction in overall inpatient LOS with a ‘traditional’ infection control intervention, such as hand hygiene or antimicrobial stewardship, improves results further than reducing LOS on its own. Conclusion Implementing a LOS-focused intervention would be a practical challenge, especially for clinicians who already juggle high demand. However, it is not unattainable with the right local endorsement and could have significant benefits for health services.

Introduction Healthcare decision-makers are increasingly expected to balance increasing demand for health services with a finite budget. The role of economic evaluation in healthcare is increasing and this research provides decision-makers with new information about the management of Clostridium difficile infection, from an economic perspective. Methods A model-based economic evaluation was undertaken to identify the most cost-effective healthcare intervention relating to the reduction of Clostridium difficile transmission. Efficacy evidence was synthesised from the literature and was used to inform the effectiveness of both bundled approaches and stand-alone interventions, where appropriate intervention combinations were coupled together. Changes in health outcomes were estimated by combining information about intervention effectiveness and its subsequent impact on quality of life. Results A bundled approach of improving hand hygiene and environmental cleaning produces the best combination of increased health benefits and cost-savings. It has the highest mean net monetary benefit when compared to all other interventions. This intervention remains the optimal decision under different clinical circumstances, such as when mortality rate and patient length of stay are increased. Bundled interventions offered the best opportunity for health improvements. Conclusion These findings provide healthcare decision-makers with novel information about the allocation of scarce resources relating to Clostridium difficile. If investments are not made in interventions that clearly yield gains in health outcomes, the allocation and use of scarce healthcare resources is inappropriate and improvements in health outcomes will be forgone.

Background Malaria causes significant morbidity and mortality worldwide. There are several preventive measures that are currently employed, including insecticide-treated nets (ITNs, including long-lasting insecticidal nets and insecticidal-treated bed nets), indoor residual spraying (IRS), prophylactic drugs (PD), and untreated nets (UN). However, it is unclear which measure is the most effective for malaria prevention. We therefore undertook a network meta-analysis to compare the efficacy of different preventive measures on incidence of malaria infection. Methods A systematic literature review was undertaken across four medical and life sciences databases (PubMed, Cochrane Central, Embase, and Web of Science) from their inception to July 2016 to compare the effectiveness of different preventive measures on malaria incidence. Data from the included studies were analysed for the effectiveness of several measures against no intervention (NI). This was carried out using an automated generalized pairwise modeling (GPM) framework for network meta-analysis to generate mixed treatment effects against a common comparator of no intervention (NI). Results There were 30 studies that met the inclusion criteria from 1998–2016. The GPM framework led to a final ranking of effectiveness of measures in the following order from best to worst: PD, ITN, IRS and UN, in comparison with NI. However, only ITN (RR: 0.49, 95% CI: 0.32–0.74) showed precision while other methods [PD (RR: 0.24, 95% CI: 0.004–15.43), IRS (RR: 0.55, 95% CI: 0.20–1.56) and UN (RR: 0.73, 95% CI: 0.28–1.90)] demonstrating considerable uncertainty associated with their point estimates. Conclusion Current evidence is strong for the protective effect of ITN interventions in malaria prevention. Even though ITNs were found to be the only preventive measure with statistical support for their effectiveness, the role of other malaria control measures may be important adjuncts in the global drive

Background: Malaria causes significant morbidity and mortality worldwide. There are several preventive measures that are currently employed, including insecticide-treated nets (ITNs, including long-lasting insecticidal nets and insecticidal-treated bed nets), indoor residual spraying (IRS), prophylactic drugs (PD), and untreated nets (UN). However, it is unclear which measure is the most effective for malaria prevention. We therefore undertook a network meta-analysis to compare the efficacy of different preventive measures on incidence of malaria infection. Methods: A systematic literature review was undertaken across four medical and life sciences databases (PubMed, Cochrane Central, Embase, and Web of Science) from their inception to July 2016 to compare the effectiveness of different preventive measures on malaria incidence. Data from the included studies were analysed for the effectiveness of several measures against no intervention (NI). This was carried out using an automated generalized pairwise modeling (GPM) framework for network meta-analysis to generate mixed treatment effects against a common comparator of no intervention (NI). Results: There were 30 studies that met the inclusion criteria from 1998–2016. The GPM framework led to a final ranking of effectiveness of measures in the following order from best to worst: PD, ITN, IRS and UN, in comparison with NI. However, only ITN (RR: 0.49, 95% CI: 0.32–0.74) showed precision while other methods [PD (RR: 0.24, 95% CI: 0.004–15.43), IRS (RR: 0.55, 95% CI: 0.20–1.56) and UN (RR: 0.73, 95% CI: 0.28–1.90)] demonstrating considerable uncertainty associated with their point estimates. Conclusion: Current evidence is strong for the protective effect of ITN interventions in malaria prevention. Even though ITNs were found to be the only preventive measure with statistical support for their effectiveness, the role of other malaria control measures may be important adjuncts in the global drive to eliminate malaria.

Background: In this study, we aimed to identify the effect of market-level risk factors on avian influenza (AI) infection in poultry and humans and generate evidence that will inform AI prevention and control programs at live bird markets (LBMs). Methods: We performed a systematic literature review in both English and Chinese search engines. We estimated the pooled odds ratios of biosecurity indicators relating to AI infections at market level using a quality effects (QE) meta-analysis model. Results: Biosecurity measures effective at reducing AI market contamination and poultry infection at LBMs include smaller market size, selling single poultry species and separating different species, performing cleaning and disinfection and market closures, ban on overnight storage, and sourcing poultry from local areas. Our meta-analysis indicates that higher risk of exposure to AI infection occurs in workers at retail LBMs, female workers, and those who contact ducks, conduct cleaning, slaughtering, defeathering, or evisceration. Conclusions: The most effective strategies to reduce AI market contamination identified in this study should target larger LBMs that are located at noncentral city areas and sell and slaughter multispecies of live poultry. Live bird market workers directly involved in cleaning and poultry processing tasks should participate in occupational health and safety programs.

Background: Tuberculosis (TB) transmission often occurs within a household or community, leading to heterogeneous spatial patterns. However, apparent spatial clustering of TB could reflect ongoing transmission or co-location of risk factors and can vary considerably depending on the type of data available, the analysis methods employed and the dynamics of the underlying population. Thus, we aimed to review methodological approaches used in the spatial analysis of TB burden. Methods: We conducted a systematic literature search of spatial studies of TB published in English using Medline, Embase, PsycInfo, Scopus and Web of Science databases with no date restriction from inception to 15 February 2017. The protocol for this systematic review was prospectively registered with PROSPERO (CRD42016036655). Results: We identified 168 eligible studies with spatial methods used to describe the spatial distribution (n = 154), spatial clusters (n = 73), predictors of spatial patterns (n = 64), the role of congregate settings (n = 3) and the household (n = 2) on TB transmission. Molecular techniques combined with geospatial methods were used by 25 studies to compare the role of transmission to reactivation as a driver of TB spatial distribution, finding that geospatial hotspots are not necessarily areas of recent transmission. Almost all studies used notification data for spatial analysis (161 of 168), although none accounted for undetected cases. The most common data visualisation technique was notification rate mapping, and the use of smoothing techniques was uncommon. Spatial clusters were identified using a range of methods, with the most commonly employed being Kulldorff's spatial scan statistic followed by local Moran's I and Getis and Ord's local Gi(d) tests. In the 11 papers that compared two such methods using a single dataset, the clustering patterns identified were often inconsistent. Classical regression models that did not account for spatial dependence were commonly

Mental health disorders, social stress, and poor health-related quality of life are commonly reported among people with tuberculosis (TB). We conducted a systematic review and meta-analysis to quantify mental health disorders, social stressors, and health-related quality of life in patients with multidrug-resistant tuberculosis (MDR-TB).

Soil-transmitted helminths (STHs) including Ascaris lumbricoides, Necator americanus, Ancylostoma spp. and Trichuris trichiura are cause of significant global morbidity. To mitigate their disease burden, at-risk groups in endemic regions receive periodic mass drug administration using anthelmintics, most commonly albendazole and mebendazole. Assessing the efficacy of anthelmintic drugs is important for confirming that these regimens are working effectively and that drug resistance has not emerged. In this study we aimed to characterise the therapeutic efficacy of albendazole against Ascaris spp. and N. americanus in Timor-Leste, using a quantitative polymerase chain reaction (qPCR) method for parasite detection and quantification.

Environmental enteropathy (EE) is characterised by subclinical inflammation and hyperpermeability of the small intestine, hypothesised to be caused by recurrent ingestion of faecal bacteria. It has been suggested that EE may be a contributor to malnutrition and growth delays seen in children living in unsanitary conditions. We measured putative faecal EE markers myeloperoxidase (MPO) (ng/mL) and alpha-1-antitrypsin (AAT) (mg/g) in stool samples collected from 133 children aged 1–5 years in 16 communities enrolled in the WASH for WORMS randomised controlled trial in Timor-Leste. Samples were collected two years after a community-wide water, sanitation and hygiene (WASH) intervention that was integrated with regular deworming. Mixed effects multivariable linear regression models were used to examine the impact of the study intervention and of various WASH and infection-related factors on EE biomarkers. Children who lived in communities that received both the WASH intervention and deworming had similar AAT values as those who lived in communities that received only deworming (regression coefficient -0.14, p = 0.583), but they had a trend towards lower MPO values (coeff -0.51, p = 0.055). Younger children showed significantly higher MPO levels (coeff: -0.29, p = 0.002). No WASH variables or parasitic infections were associated with AAT levels. Household water being stored in covered containers was associated with lower MPO levels (coeff -1.75, p = 0.046). We found little evidence that a community-based WASH intervention had an impact on EE over a two-year period.

Background Soil-transmitted helminths (STH) infect nearly 1.5 billion individuals globally, and contribute to poor physical and cognitive development in children. STH control programs typically consist of regular delivery of anthelminthic drugs, targeting school-aged children. Expanding STH control programs community-wide may improve STH control among school-aged children, and combining deworming with improvements to water, sanitation and hygiene (WASH) may further reduce transmission. The (S)WASH-D for Worms pilot study aims to compare the differential impact of integrated WASH and deworming programs when implemented at primary schools only versus when additionally implemented community-wide. Methodology/Principal findings A two-arm, non-randomized cluster intervention study was conducted. Six communities were identified by partner WASH agencies and enrolled in the study. All communities received a school-based WASH and deworming program, while three additionally received a community-based WASH and deworming program. STH infections were measured in school-aged children at baseline and six months after deworming. Over 90% of eligible children were recruited for the study, of whom 92.3% provided stool samples at baseline and 88.9% at follow-up. The school WASH intervention improved school sanitation, while the community WASH intervention reduced open defecation from 50.4% (95% CI 41.8–59.0) to 23.5% (95% CI 16.7–32.0). There was a trend towards reduced odds of N. americanus infection among children who received the community-wide intervention (OR 0.42, 95% CI 0.07–2.36, p = 0.32). Conclusions This pilot study provides proof of principle for testing the hypothesis that community-wide STH control programs have a greater impact on STH infections among children than school-based programs, and supports the rationale for conducting a full-scale cluster randomized controlled trial. High recruitment and participation rates and successful implementation of school WASH program

Background: Viet Nam has made tremendous progress towards reducing mortality and morbidity associated with malaria in recent years. Despite the success in malaria control, there has been a recent increase in cases in some provinces. In order to understand the changing malaria dynamics in Viet Nam and measure progress towards elimination, the aim of this study was to describe and quantify spatial and temporal trends of malaria by species at district level across the country. Methods: Malaria case reports at the Viet Nam National Institute of Malariology, Parasitology, and Entomology were reviewed for the period of January 2009 to December 2015. The population of each district was obtained from the Population and Housing Census-2009. A multivariate (insecticide-treated mosquito nets [ITN], indoor residual spraying [IRS], maximum temperature), zero-inflated, Poisson regression model was developed with spatial and spatiotemporal random effects modelled using a conditional autoregressive prior structure, and with posterior parameters estimated using Bayesian Markov chain Monte Carlo simulation with Gibbs sampling. Covariates included in the models were coverage of intervention (ITN and IRS) and maximum temperature. Results: There was a total of 57,713 Plasmodium falciparum and 32,386 Plasmodium vivax cases during the study period. The ratio of P. falciparum to P. vivax decreased from 4.3 (81.0% P. falciparum; 11,121 cases) in 2009 to 0.8 (45.0% P. falciparum; 3325 cases) in 2015. Coverage of ITN was associated with decreased P. falciparum incidence, with a 1.1% (95% credible interval [CrI] 0.009%, 1.2%) decrease in incidence for 1% increase in the ITN coverage, but this was not the case for P. vivax, nor was it the case for IRS coverage. Maximum temperature was associated with increased incidence of both species, with a 4% (95% CrI 3.5%, 4.3%) and 1.6% (95% CrI 0.9%, 2.0%) increase in P. falciparum and P. vivax incidence for a temperature increase of 1 °C, respectively.

Background: Periodic mass distribution of benzimidazole anthelminthic drugs is the key strategy to control soil-transmitted helminths (STH) globally. However, benzimidazoles have low efficacy against Trichuris trichiura, and there are concerns about benzimidazole resistance potentially emerging in humans. Therefore, identifying alternative drug regimens is a pressing priority. We present a systematic review and network meta-analysis, comparing the efficacy of 21 different anthelminthic drug regimens, including standard, novel, and combination treatments. Methods: We searched PubMed, MEDLINE, Embase, Web of Science, and Cochrane databases and identified studies comparing anthelminthic treatments to each other or placebo. The outcomes calculated were relative risk (RR) of cure and difference in egg reduction rates (dERR). We used an automated generalized pair-wise modelling framework to generate mixed treatment effects against a common comparator, the current standard treatment (single-dose albendazole). This study is registered with PROSPERO (CRD42016050739). Findings: Our search identified 4876 studies, of which 114 were included in meta-analysis. Results identified several drug combinations with higher efficacy than single-dose albendazole for T. trichiura, including albendazole-ivermectin (RR of cure 3.22, 95%CI 1.84-5.63; dERR 0.97, 95%CI 0.21-1.74), albendazole-oxantel pamoate (RR 5.07, 95%CI 1.65-15.59; dERR 0.51, 95%CI 0.450-0.52), mebendazole-ivermectin (RR 3.37, 95%CI 2.20-5.16), and tribendimidine-oxantel pamoate (RR 4.06, 95%CI 1.30-12.64). Interpretation: There are several promising drug combinations that may enhance the impact of STH control programs on T. trichiura, without compromising efficacy against A. lumbricoides and hookworm. We suggest further, large-scale trials of these drug combinations and consideration of their use in STH control programs where T. trichiura is present.

Original article published in "Infectious Diseases of Poverty, 5, Article number: 65 1-10."After publication of this article [1] it was noticed that the wrong figure was used for Fig. 3. Please see the correct Fig. 3 below.

Background Soil-transmitted helminths (STH) are the most common parasitic infections in impoverished communities, particularly among children. Current STH control is through school-based mass drug administration (MDA), which in the Philippines is done twice annually. As expected, MDA has decreased the intensity and prevalence of STH over time. As a result, the common Kato Katz (KK) thick smear method of detecting STH is less effective because it lacks sensitivity in low intensity infections, making it difficult to measure the impact of deworming programs. Methodology/Principal findings A cross-sectional study was carried out over a four-week period from October 27, 2014 until November 20, 2014 in Laguna province, the Philippines. Stool samples were collected from 263 schoolchildren, to determine the prevalence of STH and compare diagnostic accuracy of multiplex quantitative polymerase chain reaction (qPCR) with the KK. A large discrepancy in the prevalence between the two techniques was noted for the detection of at least one type of STH infection (33.8% by KK vs. 78.3% by qPCR), Ascaris lumbricoides (20.5% by KK vs. 60.8% by qPCR) and Trichuris trichiura (23.6% by KK vs. 38.8% by qPCR). Considering the combined results of both methods, the prevalence of at least one type of helminth infection, A. lumbricoides, and T. trichiura were 83.3%, 67.7%, and 53.6%, respectively. Sensitivity of the qPCR for detecting at least one type of STH infection, A. lumbricoides, and T. trichiura were 94.1%, 89.9%, and 72.3% respectively; whereas KK sensitivity was 40.6%, 30.3%, and 44.0%, respectively. The qPCR method also detected infections with Ancylostoma spp. (4.6%), Necator americanus (2.3%), and Strongyloides stercoralis (0.8%) that were missed by KK. Conclusion/Significance qPCR may provide new and important diagnostic information to improve assessment of the effectiveness and impact of integrated control strategies particularly in areas where large-scale

Background Bidirectional signalling between the brain and the gastrointestinal tract is regulated at neural, hormonal, and immunological levels. Recent studies have shown that helminth infections can alter the normal gut microbiota. Studies have also shown that the gut microbiota is instrumental in the normal development, maturation and function of the brain. The pathophysiological pathways by which helminth infections contribute to altered cognitive function remain poorly understood. Discussion We put forward the hypothesis that gastrointestinal infections with parasitic worms, such as helminths, induce an imbalance of the gut-brain axis, which, in turn, can detrimentally manifest in brain development. Factors supporting this hypothesis are: 1) research focusing on intelligence and school performance in school-aged children has shown helminth infections to be associated with cognitive impairment, 2) disturbances in gut microbiota have been shown to be associated with important cognitive developmental effects, and 3) helminth infections have been shown to alter the gut microbiota structure. Evidence on the complex interactions between extrinsic (parasite) and intrinsic (host-derived) factors has been synthesised and discussed. Summary While evidence in favour of the helminth-gut microbiota-central nervous system hypothesis is circumstantial, it would be unwise to rule it out as a possible mechanism by which gastrointestinal helminth infections induce childhood cognitive morbidity. Further empirical studies are necessary to test an indirect effect of helminth infections on the modulation of mood and behaviour through its effects on the gut microbiota.

BACKGROUND Surgical interventions save lives and are important focus for health services research worldwide. Investigating variation in postoperative mortality may improve understanding of unwarranted variations and promote safety and quality in surgical care. We aimed to evaluate trends of in-hospital mortality rates among adult inpatients receiving major elective surgeries and determine the variation in mortality among New South Wales (NSW) public hospitals. MATERIALS AND METHODS In this study, we used the all-inclusive population-based NSW Admitted Patient Data from July 2001 to June 2014. We retrospectively included adult patients aged 18 + years receiving Abdominal Aortic Aneurysm (AAA) repair, Peripheral bypass, Colorectal surgeries, Joint replacement, Spinal surgeries, or Cardiac surgeries. The primary outcome was in-hospital mortality for selected surgeries. Changes in mortality rates over time and hospital standardised mortality rates were modelled using multivariate logistic regression models adjusting for case-mix factors. RESULTS Over 13-year study period, the in-hospital mortality rates declined annually by 6.4% (95% Confidence Interval (CI): 4.3, 8.4) for Colorectal surgery by 5.7% (95%CI: 2.0, 9.3) for Joint replacement and by 4.2% (95%CI: 1.9, 6.4) for Cardiac surgery. After controlling for patient-level factors, little variation was observed among hospitals for in-hospital mortality. There was a greater variability for cardiac surgery compared with the other surgical groups but no outlier hospital was consistently associated with significantly higher than expected mortality rate. CONCLUSIONS Mortality has declined for major surgeries in the past 15 years. There was some variation among hospitals regarding in-hospital mortality that was mostly explained by patients demographic and admission characteristics. Our findings are reassuring for patients and contribute to knowledge that can help further improve surgical care.

BACKGROUND Clostridium difficile infections are common among hospitalised patients, with some infections acquired in hospital and others in the community. International guidelines classify cases as hospital-acquired if symptom onset occurs >2 days after admission. This classification informs surveillance and infection control, but has not been verified by empirical or modelling studies. AIMS To assess current classification of C. difficile acquisition using a simulation model as a gold standard. METHODS We simulated C. difficile transmission in a range of hospital scenarios. We calculated the sensitivity, specificity and precision of classifications that use cut-offs ranging from 0.25 hours to 40 days. We identified the optimal cut-off that correctly estimated the proportion of cases that were hospital acquired and the balanced cut-off that had equal sensitivity and specificity. FINDINGS The recommended two-day cut-off overestimated the incidence of hospital-acquired cases in all scenarios and by >100% in the base scenario. The two-day cut-off had good sensitivity (96%) but poor specificity (48%) and precision (52%) to identify cases acquired during the current hospitalisation. A five-day cut-off was balanced and a six-day cut-off was optimal in the base scenario. The optimal and balanced cut-offs were more than two days for nearly all scenarios considered (ranges four to nine days and two to eight days). CONCLUSIONS Current guidelines for classifying C. difficile infections overestimate the proportion of cases acquired in hospital in all model scenarios. To reduce misclassification bias, an infection should be classified as being acquired prior to admission if symptoms begin within five days of admission.

Background The elimination of malaria requires high-quality surveillance data to enable rapid detection and response to individual cases. Evaluation of the performance of a national malaria surveillance system could identify shortcomings which, if addressed, will improve the surveillance program for malaria elimination. Methods Case-level data for the period 2005–2014 were extracted from the China National Notifiable Infectious Disease Reporting Information System and Malaria Enhanced Surveillance Information System. The occurrence of cases, accuracy and timeliness of case diagnosis, reporting and investigation, were assessed and compared between the malaria control stage (2005–2010) and elimination stage (2011–2014) in mainland China. Results A total of 210 730 malaria cases were reported in mainland China in 2005–2014. The average annual incidence declined dramatically from 2.5 per 100 000 people at the control stage to 0.2 per 100 000 at the elimination stage, but the proportion of migrant cases increased from 9.8 % to 41.0 %. Since the initiation of the National Malaria Elimination Programme in 2010, the overall proportion of cases diagnosed by laboratory testing consistently improved, with the highest of 99.0 % in 2014. However, this proportion was significantly lower in non-endemic provinces (79.0 %) than that in endemic provinces (91.4 %) during 2011–2014. The median interval from illness onset to diagnosis was 3 days at the elimination stage, with one day earlier than that at the control stage. Since 2011, more than 99 % cases were reported within 1 day after being diagnosed, while the proportion of cases that were reported within one day after diagnosis was lowest in Tibet (37.5 %). The predominant source of cases reporting shifted from town-level hospitals at the control stage (67.9 % cases) to city-level hospitals and public health institutes at the eliminate stage (69.4 % cases). The proportion of investigation within 3 days after case reporting has impr