282 results on '"Gray, DJ"'
Search Results
2. The COVID-19 vaccination campaign in Bhutan: strategy and enablers
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Tsheten, T, Tenzin, P, Clements, ACA, Gray, DJ, Ugyel, L, Wangdi, K, Tsheten, T, Tenzin, P, Clements, ACA, Gray, DJ, Ugyel, L, and Wangdi, K
- Abstract
Bhutan has reported a total of 2596 COVID-19 cases and three deaths as of September 15, 2021. With support from India, the United States, Denmark, the People’s Republic of China, Croatia and other countries, Bhutan was able to conduct two rounds of nationwide vaccination campaign. While many countries struggle to overcome vaccine refusal or hesitancy due to complacency, a lack of trust, inconvenience and fear, escalated in some countries by anti-vaccine groups, Bhutan managed to inoculate more than 95% of its eligible populations in two rounds of vaccination campaign. Enabling factors of this successful vaccination campaign were strong national leadership, a well-coordinated national preparedness plan, and high acceptability of vaccine due to effective mass communication and social engagement led by religious figures, volunteers and local leaders. In this short report, we described the national strategic plan and enabling factors that led to the success of this historical vaccination campaign.
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- 2022
3. HTLV-I and Strongyloides in Australia: The worm lurking beneath.
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Rollinson, D, Stothard, JR, Gordon, CA, Shield, JM, Bradbury, RS, Muhi, S, Page, W, Judd, JA, Lee, R, Biggs, B-A, Ross, K, Kurscheid, J, Gray, DJ, McManus, DP, Rollinson, D, Stothard, JR, Gordon, CA, Shield, JM, Bradbury, RS, Muhi, S, Page, W, Judd, JA, Lee, R, Biggs, B-A, Ross, K, Kurscheid, J, Gray, DJ, and McManus, DP
- Abstract
Strongyloidiasis and HTLV-I (human T-lymphotropic virus-1) are important infections that are endemic in many countries around the world with an estimated 370 million infected with Strongyloides stercoralis alone, and 5-10 million with HTVL-I. Co-infections with these pathogens are associated with significant morbidity and can be fatal. HTLV-I infects T-cells thus causing dysregulation of the immune system which has been linked to dissemination and hyperinfection of S. stercoralis leading to bacterial sepsis which can result in death. Both of these pathogens are endemic in Australia primarily in remote communities in Queensland, the Northern Territory, and Western Australia. Other cases in Australia have occurred in immigrants and refugees, returned travellers, and Australian Defence Force personnel. HTLV-I infection is lifelong with no known cure. Strongyloidiasis is a long-term chronic disease that can remain latent for decades, as shown by infections diagnosed in prisoners of war from World War II and the Vietnam War testing positive decades after they returned from these conflicts. This review aims to shed light on concomitant infections of HTLV-I with S. stercoralis primarily in Australia but in the global context as well.
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- 2021
4. Development of a risk score for prediction of poor treatment outcomes among patients with multidrug-resistant tuberculosis
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Ehtesham, HS, Alene, KA, Viney, K, Gray, DJ, McBryde, ES, Xu, Z, Clements, ACA, Ehtesham, HS, Alene, KA, Viney, K, Gray, DJ, McBryde, ES, Xu, Z, and Clements, ACA
- Abstract
BACKGROUND: Treatment outcomes among patients treated for multidrug-resistant tuberculosis (MDR-TB) are often sub-optimal. Therefore, the early prediction of poor treatment outcomes may be useful in patient care, especially for clinicians when they have the ability to make treatment decisions or offer counselling or additional support to patients. The aim of this study was to develop a simple clinical risk score to predict poor treatment outcomes in patients with MDR-TB, using routinely collected data from two large countries in geographically distinct regions. METHODS: We used MDR-TB data collected from Hunan Chest Hospital, China and Gondar University Hospital, Ethiopia. The data were divided into derivation (n = 343; 60%) and validation groups (n = 227; 40%). A poor treatment outcome was defined as treatment failure, lost to follow up or death. A risk score for poor treatment outcomes was derived using a Cox proportional hazard model in the derivation group. The model was then validated in the validation group. RESULTS: The overall rate of poor treatment outcome was 39.5% (n = 225); 37.9% (n = 86) in the derivation group and 40.5% (n = 139) in the validation group. Three variables were identified as predictors of poor treatment outcomes, and each was assigned a number of points proportional to its regression coefficient. These predictors and their points were: 1) history of taking second-line TB treatment (2 points), 2) resistance to any fluoroquinolones (3 points), and 3) smear did not convert from positive to negative at two months (4 points). We summed these points to calculate the risk score for each patient; three risk groups were defined: low risk (0 to 2 points), medium risk (3 to 5 points), and high risk (6 to 9 points). In the derivation group, poor treatment outcomes were reported for these three groups as 14%, 27%, and 71%, respectively. The area under the receiver operating characteristic curve for the point system in the derivation group was 0.69 (95
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- 2020
5. Epidemiology of soil-transmitted helminth infections in Semarang, Central Java, Indonesia
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Chai, J-Y, Kurscheid, J, Laksono, B, Park, MJ, Clements, ACA, Sadler, R, McCarthy, JS, Nery, SV, Soares-Magalhaes, R, Halton, K, Hadisaputro, S, Richardson, A, Indjein, L, Wangdi, K, Stewart, DE, Gray, DJ, Chai, J-Y, Kurscheid, J, Laksono, B, Park, MJ, Clements, ACA, Sadler, R, McCarthy, JS, Nery, SV, Soares-Magalhaes, R, Halton, K, Hadisaputro, S, Richardson, A, Indjein, L, Wangdi, K, Stewart, DE, and Gray, DJ
- Abstract
Soil-transmitted helminth (STH) infections are endemic in Indonesia. However, prevalence data for many parts of the country are incomplete. The aim of this study was to determine human STH prevalence and knowledge and practices relating to STH risk behaviour, to provide a current view of the status of STH infection in rural communities in Central Java. A cross-sectional survey of 16 villages was conducted in Semarang, Central Java in 2015. Demographic and household data together with information about knowledge and practices relating to STH and hygiene were elicited through face-to-face interviews. Stool samples were collected and examined using the flotation method. Children (aged 2–12 years) also had their haemoglobin (Hb) levels, height and weight data collected, and BMI estimated. Data were analysed using univariate logistic regression analysis. A total of 6,466 individuals with a mean age of 33.5 years (range: 2–93) from 2,195 households were interviewed. The overall prevalence of STH was 33.8% with Ascaris lumbricoides (roundworm) the predominant nematode identified (prevalence = 26.0%). Hookworm and Trichuris trichiura (whipworm) were found in 7.9% and 1.8% of participants, respectively. Females were at increased odds of infection with A. lumbricoides (adjusted OR 1.14, 95% CI [1.02–1.29], p = 0.02). Adults in age groups 51–60 and over 60 years had the highest odds of being infected with hookworm (adjusted OR 3.01, 95% CI [1.84–4.91], p<0.001 and adjusted OR 3.79, 95% CI [2.30–6.26], p<0.001, respectively) compared to 6–12 year olds. Farmers also had higher odds of being infected with hookworm (adjusted OR 2.36, 95% CI [1.17–4.76], p = 0.02) compared to other occupation categories. Poverty (OR 2.14, 95% CI [1.77–2.58], p<0.001), overcrowding (OR 1.35, 95% CI [1.27–1.44], p<0.001), goat ownership (OR 1.61, 95% CI [1.10–2.41], p = 0.02) and the presence of dry floor space in the home (OR 0.73, 95% CI [0.58–0.91], p = 0.01) were all household factors significant
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- 2020
6. Giardia duodenalis infection in the context of a community-based deworming and water, sanitation and hygiene trial in Timor-Leste
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Aw, JYH, Clarke, NE, McCarthy, JS, Traub, RJ, Amaral, S, Huque, MH, Andrews, RM, Gray, DJ, Clements, ACA, Vaz Nery, S, Aw, JYH, Clarke, NE, McCarthy, JS, Traub, RJ, Amaral, S, Huque, MH, Andrews, RM, Gray, DJ, Clements, ACA, and Vaz Nery, S
- Abstract
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. Methods: The WASH for WORMS cluster randomised controlled trial was conducted in remote communities in Manufahi municipality, Timor-Leste, between 2012 and 2016. All study communities received four rounds of deworming with albendazole at six-monthly intervals. Half were randomised to additionally receive a community-level WASH intervention following study baseline. We measured G. duodenalis infection in study participants every six months for two years, immediately prior to deworming, as a pre-specified secondary outcome of the trial. WASH access and behaviours were measured using questionnaires. Results: There was no significant change in G. duodenalis prevalence in either study arm between baseline and the final study follow-up. We found no additional benefit of the community-level WASH intervention on G. duodenalis infection (relative risk: 1.05, 95% CI: 0.72-1.54). Risk factors for G. duodenalis infection included living in a household with a child under five years of age (adjusted odds ratio, aOR: 1.35, 95% CI: 1.04-1.75), living in a household with more than six people (aOR: 1.32, 95% CI: 1.02-1.72), and sampling during the rainy season (aOR: 1.23, 95% CI: 1.04-1.45). Individuals infected with the hookworm Necator americanus were less likely to have G. duodenalis infection (aOR: 0.71, 95% CI: 0.57-0.88). Conclusions: Prevalence of G. duodenalis was not aff
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- 2019
7. A cluster-randomised controlled trial comparing school and community-based deworming for soil transmitted helminth control in school-age children: the CoDe-STH trial protocol
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Clarke, NE, Dinh, N-N, Traub, RJ, Clements, ACA, Halton, K, Anderson, RM, Gray, DJ, Coffeng, LE, Kaldor, JM, Nery, SV, Clarke, NE, Dinh, N-N, Traub, RJ, Clements, ACA, Halton, K, Anderson, RM, Gray, DJ, Coffeng, LE, Kaldor, JM, and Nery, SV
- Abstract
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
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- 2019
8. Mapping tuberculosis treatment outcomes in Ethiopia
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Alene, KA, Viney, K, Gray, DJ, McBryde, ES, Wagnew, M, Clements, ACA, Alene, KA, Viney, K, Gray, DJ, McBryde, ES, Wagnew, M, and Clements, ACA
- Abstract
BACKGROUND: Tuberculosis (TB) is the leading cause of death from an infectious disease in Ethiopia, killing more than 30 thousand people every year. This study aimed to determine whether the rates of poor TB treatment outcome varied geographically across Ethiopia at district and zone levels and whether such variability was associated with socioeconomic, behavioural, health care access, or climatic conditions. METHODS: A geospatial analysis was conducted using national TB data reported to the health management information system (HMIS), for the period 2015-2017. The prevalence of poor TB treatment outcomes was calculated by dividing the sum of treatment failure, death and loss to follow-up by the total number of TB patients. Binomial logistic regression models were computed and a spatial analysis was performed using a Bayesian framework. Estimates of parameters were generated using Markov chain Monte Carlo (MCMC) simulation. Geographic clustering was assessed using the Getis-Ord Gi* statistic, and global and local Moran's I statistics. RESULTS: A total of 223,244 TB patients were reported from 722 districts in Ethiopia during the study period. Of these, 63,556 (28.5%) were cured, 139,633 (62.4%) completed treatment, 6716 (3.0%) died, 1459 (0.7%) had treatment failure, and 12,200 (5.5%) were lost to follow-up. The overall prevalence of a poor TB treatment outcome was 9.0% (range, 1-58%). Hot-spots and clustering of poor TB treatment outcomes were detected in districts near the international borders in Afar, Gambelia, and Somali regions and cold spots were detected in Oromia and Amhara regions. Spatial clustering of poor TB treatment outcomes was positively associated with the proportion of the population with low wealth index (OR: 1.01; 95%CI: 1.0, 1.01), the proportion of the population with poor knowledge about TB (OR: 1.02; 95%CI: 1.01, 1.03), and higher annual mean temperature per degree Celsius (OR: 1.15; 95% CI: 1.08, 1.21). CONCLUSIONS: This study showed signif
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- 2019
9. Risk factors for multidrug-resistant tuberculosis in northwest Ethiopia: A case-control study
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Alene, KA, Viney, K, McBryde, ES, Gray, DJ, Melku, M, Clements, ACA, Alene, KA, Viney, K, McBryde, ES, Gray, DJ, Melku, M, and Clements, ACA
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Ethiopia is one of 30-high burden multidrug-resistant tuberculosis (MDR-TB) countries globally. The aim of this study was to describe the characteristics of patients with MDR-TB and to investigate risk factors for MDR-TB relative to having drug-susceptible tuberculosis (TB), in northwest Ethiopia. A hospital-based, unmatched case-control study was conducted. Cases were all MDR-TB patients (i.e., resistant to at least rifampicin and isoniazid) who were confirmed by culture and drug-susceptibility testing whilst enrolled on treatment at Gondar University Hospital. Controls were all drug-susceptible tuberculosis (DS-TB) patients who were confirmed by Gene Xpert MTB/RIF at Gondar University Hospital. Univariable and multivariable logistic regression models were used for comparisons, and odds ratios with 95% confidence intervals (CI) were computed to measure the strength of association between the dependent and independent variables. A total of 452 patients (242 MDR-TB and 210 DS-TB) were included in this study. The mean age of the study participants was 33 years (SD ± 14 years). Approximately one-fifth (78, 17%) of all study participants were human immunodeficiency virus (HIV) positive; 21% (51) of cases and 13% (27) of controls. Risk factors associated with MDR-TB were a history of previous TB treatment (Adjusted Odds Ratio (AOR): 83.8; 95% CI: 40.7, 172.5), low educational status (AOR: 5.32; 95% CI: 1.43, 19.81); and ages less than 20 years (AOR: 9.01; 95% CI: 2.30, 35.25) and 21-30 years (AOR: 2.61; 95% CI: 1.02, 6.64). HIV infection was also significantly associated with MDR-TB among new TB patients (AOR: 5.55; 95% CI: 1.17, 26.20). This study shows that clinical and demographic features can be used to indicate higher risks of drug resistance in this setting.
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- 2019
10. Predicted short and long-term impact of deworming and water, hygiene, and sanitation on transmission of soil-transmitted helminths
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Coffeng, Luc, Nery, SV, Gray, DJ, Bakker, Roel, de Vlas, Sake, Clements, ACA, and Public Health
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- 2018
11. (S)WASH-D for Worms: A pilot study investigating the differential impact of school-versus community-based integrated control programs for soil-transmitted helminths
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Mackenzie, CD, Clarke, NE, Clements, ACA, Amaral, S, Richardson, A, McCarthy, JS, McGown, J, Bryan, S, Gray, DJ, Nery, SV, Mackenzie, CD, Clarke, NE, Clements, ACA, Amaral, S, Richardson, A, McCarthy, JS, McGown, J, Bryan, S, Gray, DJ, and Nery, SV
- Abstract
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 prog
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- 2018
12. Use of quantitative PCR to assess the efficacy of albendazole against Necator americanus and Ascaris spp. in Manufahi District, Timor-Leste
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Nery, SV, Qi, J, Llewellyn, S, Clarke, NE, Traub, R, Gray, DJ, Vallely, AJ, Williams, GM, Andrews, RM, McCarthy, JS, Clements, ACA, Nery, SV, Qi, J, Llewellyn, S, Clarke, NE, Traub, R, Gray, DJ, Vallely, AJ, Williams, GM, Andrews, RM, McCarthy, JS, and Clements, ACA
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BACKGROUND: 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. RESULTS: A total of 314 participants from 8 communities in Timor-Leste provided stool samples before and 10-14 days after the administration of a single 400 mg dose of albendazole. Helminth infection status and infection intensity (measured in Ct-values and relative fluorescence units) were determined using qPCR. Efficacy was determined by examining the cure rates and infection intensity reduction rates. Albendazole was found to be highly efficacious against Ascaris spp., with a cure rate of 91.4% (95% CI: 85.9-95.2%) and infection intensity reduction rate of 95.6% (95% CI: 88.3-100%). The drug was less efficacious against N. americanus with a cure rate of 58.3% (95% CI: 51.4-64.9%) and infection intensity reduction rate of 88.9% (95% CI: 84.0-97.0%). CONCLUSIONS: The observed cure rates and infection intensity reduction rates obtained for Ascaris spp. and to a lower extent N. americanus, demonstrate the continued efficacy of albendazole against these species and its utility as a mass chemotherapy agent in Timor-Leste. Furthermore, this study demonstrates the usefulness of qPCR as a method to measure the efficacy of anthelminthic drugs. Additional research is necessary to translate Ct-values into eggs per gram in a systematic w
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- 2018
13. Comparison of the validity of smear and culture conversion as a prognostic marker of treatment outcome in patients with multidrug-resistant tuberculosis
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Hasnain, SE, Alene, KA, Viney, K, Yi, H, McBryde, ES, Yang, K, Bai, L, Gray, DJ, Xu, Z, Clements, ACA, Hasnain, SE, Alene, KA, Viney, K, Yi, H, McBryde, ES, Yang, K, Bai, L, Gray, DJ, Xu, Z, and Clements, ACA
- Abstract
BACKGROUND: The World Health Organization (WHO) has conditionally recommended the use of sputum smear microscopy and culture examination for the monitoring of multidrug-resistant tuberculosis (MDR-TB) treatment. We aimed to assess and compare the validity of smear and culture conversion at different time points during treatment for MDR-TB, as a prognostic marker for end-of-treatment outcomes. METHODS: We undertook a retrospective observational cohort study using data obtained from Hunan Chest Hospital, China and Gondar University Hospital, Ethiopia. The sensitivity and specificity of culture and sputum smear conversion for predicting treatment outcomes were analysed using a random-effects generalized linear mixed model. RESULTS: A total of 429 bacteriologically confirmed MDR-TB patients with a culture and smear positive result were included. Overall, 345 (80%) patients had a successful treatment outcome, and 84 (20%) patients had poor treatment outcomes. The sensitivity of smear and culture conversion to predict a successful treatment outcome were: 77.9% and 68.9% at 2 months after starting treatment (difference between tests, p = 0.007); 95.9% and 92.7% at 4 months (p = 0.06); 97.4% and 96.2% at 6 months (p = 0.386); and 99.4% and 98.9% at 12 months (p = 0.412), respectively. The specificity of smear and culture non-conversion to predict a poor treatment outcome were: 41.6% and 60.7% at 2 months (p = 0.012); 23.8% and 48.8% at 4 months (p<0.001); and 20.2% and 42.8% at 6 months (p<0.001); and 15.4% and 32.1% (p<0.001) at 12 months, respectively. The sensitivity of culture and smear conversion increased as the month of conversion increased but at the cost of decreased specificity. The optimum time points after conversion to provide the best prognostic marker of a successful treatment outcome were between two and four months after treatment commencement for smear, and between four and six months for culture. The common optimum time point for smear and culture convers
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- 2018
14. Investigations into the association between soil-transmitted helminth infections, haemoglobin and child development indices in Manufahi District, Timor-Leste
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Campbell, SJ, Nery, SV, D'Este, CA, Gray, DJ, McCarthy, JS, Traub, RJ, Andrews, RM, Llewellyn, S, Vallely, AJ, Williams, GM, Clements, ACA, Campbell, SJ, Nery, SV, D'Este, CA, Gray, DJ, McCarthy, JS, Traub, RJ, Andrews, RM, Llewellyn, S, Vallely, AJ, Williams, GM, and Clements, ACA
- Abstract
© 2017 The Author(s). Background: Timor-Leste has a high prevalence of soil-transmitted helminth (STH) infections. High proportions of the population have been reported as being anaemic, and extremely high proportions of children as stunted or wasted. There have been no published analyses of the contributions of STH to these morbidity outcomes in Timor-Leste. Methods: Using baseline cross-sectional data from 24 communities (18 communities enrolled in a cluster randomised controlled trial, and identically-collected data from six additional communities), analyses of the association between STH infections and community haemoglobin and child development indices were undertaken. Stool samples were assessed for STH using qPCR and participant haemoglobin, heights and weights were measured. Questionnaires were administered to collect demographic and socioeconomic data. Intensity of infection was categorised using correlational analysis between qPCR quantification cycle values and eggs per gram of faeces equivalents, with algorithms generated from seeding experiments. Mixed-effects logistic and multinomial regression were used to assess the association between STH infection intensity classes and anaemia, and child stunting, wasting and underweight. Results: Very high stunting (60%), underweight (60%), and wasting (20%) in children, but low anaemia prevalence (15%), were found in the study communities. STH were not significantly associated with morbidity outcomes. Male children and those in the poorest socioeconomic quintile were significantly more likely to be moderately and severely stunted. Male children were significantly more likely than female children to be severely underweight. Increasing age was also a risk factor for being underweight. Few risk factors emerged for wasting in these analyses. Conclusions: According to World Health Organization international reference standards, levels of child morbidity in this population constitute a public health emergency, although
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- 2017
15. Water, Sanitation and Hygiene (WASH) and environmental risk factors for soil-transmitted helminth intensity of infection in Timor-Leste, using real time PCR
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Campbell, SJ, Nery, SV, Wardell, R, D Este, CA, Gray, DJ, McCarthy, JS, Traub, RJ, Andrews, RM, Llewellyn, S, Vallely, AJ, Williams, GM, Clements, ACA, Campbell, SJ, Nery, SV, Wardell, R, D Este, CA, Gray, DJ, McCarthy, JS, Traub, RJ, Andrews, RM, Llewellyn, S, Vallely, AJ, Williams, GM, and Clements, ACA
- Abstract
© 2017 Campbell et al. Background: No investigations have been undertaken of risk factors for intensity of soil-transmitted helminth (STH) infection in Timor-Leste. This study provides the first analysis of risk factors for intensity of STH infection, as determined by quantitative PCR (qPCR), examining a broad range of water, sanitation and hygiene (WASH) and environmental factors, among communities in Manufahi District, Timor-Leste. Methods: A baseline cross-sectional survey of 18 communities was undertaken as part of a cluster randomised controlled trial, with additional identically-collected data from six other communities. qPCR was used to assess STH infection from stool samples, and questionnaires administered to collect WASH, demographic, and socioeconomic data. Environmental information was obtained from open-access sources and linked to infection outcomes. Mixed-effects multinomial logistic regression was undertaken to assess risk factors for intensity of Necator americanus and Ascaris infection. Results: 2152 participants provided stool and questionnaire information for this analysis. In adjusted models incorporating WASH, demographic and environmental variables, environmental variables were generally associated with infection intensity for both N. americanus and Ascaris spp. Precipitation (in centimetres) was associated with increased risk of moderate-intensity (adjusted relative risk [ARR] 6.1; 95% confidence interval [CI] 1.9–19.3) and heavy-intensity (ARR 6.6; 95% CI 3.1–14.1) N. americanus infection, as was sandy-loam soil around households (moderate-intensity ARR 2.1; 95% CI 1.0–4.3; heavy-intensity ARR 2.7; 95% CI 1.6–4.5; compared to no infection). For Ascaris, alkaline soil around the household was associated with reduced risk of moderate-intensity infection (ARR 0.21; 95% CI 0.09–0.51), and heavy-intensity infection (ARR 0.04; 95% CI 0.01–0.25). Few WASH risk factors were significant. Conclusion: In this high-prevalence setting, strong risk associ
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- 2017
16. An environmental assessment and risk map of Ascaris lumbricoides and Necator americanus distributions in Manufahi District, Timor-Leste
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de Silva, N, Wardell, R, Clements, ACA, Lal, A, Summers, D, Llewellyn, S, Campbell, SJ, McCarthy, J, Gray, DJ, Nery, SV, de Silva, N, Wardell, R, Clements, ACA, Lal, A, Summers, D, Llewellyn, S, Campbell, SJ, McCarthy, J, Gray, DJ, and Nery, SV
- Abstract
BACKGROUND: In Timor-Leste there have been intermittent and ineffective soil-transmitted helminth (STH) deworming programs since 2004. In a resource-constrained setting, having information on the geographic distribution of STH can aid in prioritising high risk communities for intervention. This study aimed to quantify the environmental risk factors for STH infection and to produce a risk map of STH in Manufahi district, Timor-Leste. METHODOLOGY/PRINCIPAL FINDINGS: Georeferenced cross-sectional data and stool samples were obtained from 2,194 participants in 606 households in 24 villages in the Manufahi District as part of cross sectional surveys done in the context of the "WASH for Worms" randomised controlled trial. Infection status was determined for Ascaris lumbricoides and Necator americanus using real-time quantitative polymerase chain reaction. Baseline infection data were linked to environmental data obtained for each household. Univariable and multivariable multilevel mixed-effects logistic regression analysis with random effects at the village and household level were conducted, with all models adjusted for age and sex. For A. lumbricoides, being a school-aged child increased the odds of infection, whilst higher temperatures in the coolest quarter of the year, alkaline soils, clay loam/loam soils and woody savannas around households were associated with decreased infection odds. For N. americanus, greater precipitation in the driest month, higher average enhanced vegetation index, age and sandy loam soils increased infection odds, whereas being female and living at higher elevations decreased the odds of infection. Predictive risk maps generated for Manufahi based upon these final models highlight the high predicted risk of N. americanus infection across the district and the more focal nature of A. lumbricoides infection. The predicted risk of any STH infection is high across the entire district. CONCLUSIONS/SIGNIFICANCE: The widespread predicted risk of any
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- 2017
17. Water, Sanitation and Hygiene (WASH) and environmental risk factors for soil-transmitted helminth intensity of infection in Timor-Leste, using real time PCR
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Bethony, JM, Campbell, SJ, Nery, SV, Wardell, R, D'Este, CA, Gray, DJ, McCarthy, JS, Traub, RJ, Andrews, RM, Llewellyn, S, Vallely, AJ, Williams, GM, Clements, ACA, Bethony, JM, Campbell, SJ, Nery, SV, Wardell, R, D'Este, CA, Gray, DJ, McCarthy, JS, Traub, RJ, Andrews, RM, Llewellyn, S, Vallely, AJ, Williams, GM, and Clements, ACA
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BACKGROUND: No investigations have been undertaken of risk factors for intensity of soil-transmitted helminth (STH) infection in Timor-Leste. This study provides the first analysis of risk factors for intensity of STH infection, as determined by quantitative PCR (qPCR), examining a broad range of water, sanitation and hygiene (WASH) and environmental factors, among communities in Manufahi District, Timor-Leste. METHODS: A baseline cross-sectional survey of 18 communities was undertaken as part of a cluster randomised controlled trial, with additional identically-collected data from six other communities. qPCR was used to assess STH infection from stool samples, and questionnaires administered to collect WASH, demographic, and socioeconomic data. Environmental information was obtained from open-access sources and linked to infection outcomes. Mixed-effects multinomial logistic regression was undertaken to assess risk factors for intensity of Necator americanus and Ascaris infection. RESULTS: 2152 participants provided stool and questionnaire information for this analysis. In adjusted models incorporating WASH, demographic and environmental variables, environmental variables were generally associated with infection intensity for both N. americanus and Ascaris spp. Precipitation (in centimetres) was associated with increased risk of moderate-intensity (adjusted relative risk [ARR] 6.1; 95% confidence interval [CI] 1.9-19.3) and heavy-intensity (ARR 6.6; 95% CI 3.1-14.1) N. americanus infection, as was sandy-loam soil around households (moderate-intensity ARR 2.1; 95% CI 1.0-4.3; heavy-intensity ARR 2.7; 95% CI 1.6-4.5; compared to no infection). For Ascaris, alkaline soil around the household was associated with reduced risk of moderate-intensity infection (ARR 0.21; 95% CI 0.09-0.51), and heavy-intensity infection (ARR 0.04; 95% CI 0.01-0.25). Few WASH risk factors were significant. CONCLUSION: In this high-prevalence setting, strong risk associations with environment
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- 2017
18. Treatment outcomes of patients with multidrug-resistant and extensively drug resistant tuberculosis in Hunan Province, China
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Alene, KA, Yi, H, Viney, K, McBryde, ES, Yang, K, Bai, L, Gray, DJ, Clements, ACA, Xu, Z, Alene, KA, Yi, H, Viney, K, McBryde, ES, Yang, K, Bai, L, Gray, DJ, Clements, ACA, and Xu, Z
- Abstract
BACKGROUND: The worldwide emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) has posed additional challenges for global tuberculosis (TB) control efforts, as limited treatment options are available and treatment outcomes are often sub-optimal. This study determined treatment outcomes among a cohort of MDR-TB and XDR-TB patients in Hunan Province, China, and identified factors associated with poor treatment outcomes. METHODS: We conducted a retrospective study using data obtained from medical records of TB patients in Hunan Chest Hospital, and from the internet-based TB management information system managed by the Tuberculosis Control Institute of Hunan Province, for the period 2011 to 2014. Treatment outcomes were assessed for patients diagnosed with MDR-TB (TB resistant to at least isoniazid and rifampicin) and XDR-TB (MDR-TB plus resistance to any fluoroquinolone and at least 1 second-line injectable drug). Cumulative incidence functions were used to estimate time to events (i.e. poor treatment outcomes, loss to follow-up, and unfavourable treatment outcomes); and a competing-risks survival regression model was used to identify predictors of treatment outcomes. RESULT: Of 481 bacteriologically-confirmed patients, with a mean age of 40 years (standard deviation SD ± 13 years), 10 (2%) had XDR-TB and the remainder (471; 98%) had MDR-TB. For the entire cohort, treatment success was 57% (n = 275); 58% (n = 272) for MDR-TB and 30% (n = 3) for XDR-TB. Overall, 27% were lost to follow-up (n = 130), 27% (n = 126) for MDR-TB and 40% (n = 4) for XDR-TB; and 16% had a poor treatment outcome (n = 76), 15% for MDR-TB and 30% (n = 3) for XDR-TB. Of the 10 XDR-TB patients, 3 (30%) completed treatment, 3 (30%) died and 4 (40%) were lost to follow-up. Of the 471 MDR-TB patients, 258 (57%) were cured, 16 (3%) completed treatment, 13 (3%) died, 60 (13%) experienced treatment failure, and 126 (27%) were lost to follow-up. Resis
- Published
- 2017
19. Water, sanitation and hygiene related risk factors for soil-transmitted helminth and Giardia duodenalis infections in rural communities in Timor-Leste
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Campbell, SJ, Nery, SV, D'Este, CA, Gray, DJ, McCarthy, JS, Traub, RJ, Andrews, RM, Llewellyn, S, Vallely, AJ, Williams, GM, Amaral, S, Clements, ACA, Campbell, SJ, Nery, SV, D'Este, CA, Gray, DJ, McCarthy, JS, Traub, RJ, Andrews, RM, Llewellyn, S, Vallely, AJ, Williams, GM, Amaral, S, and Clements, ACA
- Abstract
There is little evidence on prevalence or risk factors for soil transmitted helminth infections in Timor-Leste. This study describes the epidemiology, water, sanitation and hygiene, and socioeconomic risk factors of STH and intestinal protozoa amongst communities in Manufahi District, Timor-Leste. As part of a cluster randomised controlled trial, a baseline cross-sectional survey was conducted across 18 villages, with data from six additional villages. Stool samples were assessed for soil transmitted helminth and protozoal infections using quantitative PCR (qPCR) and questionnaires administered to collect water, sanitation and hygiene and socioeconomic data. Risk factors for infection were assessed using multivariable mixed-effects logistic regression, stratified by age group (preschool, school-aged and adult). Overall, soil transmitted helminth prevalence was 69% (95% Confidence Interval 67–71%), with Necator americanus being most common (60%; 95% Confidence Interval 58–62%) followed by Ascaris spp. (24%; 95% Confidence Interval 23–26%). Ascaris-N. americanus co-infection was common (17%; 95% Confidence Interval 15%-18%). Giardia duodenalis was the main protozoan identified (13%; 95% Confidence Interval 11–14%). Baseline water, sanitation and hygiene infrastructure and behaviours were poor. Although risk factors varied by age of participants and parasite species, risk factors for N. americanus infection included, generally, age in years, male sex, and socioeconomic quintile. Risk factors for Ascaris included age in years for children, and piped water to the yard for adults. In this first known assessment of community-based prevalence and associated risk factors in Timor-Leste, soil transmitted helminth infections were highly prevalent, indicating a need for soil transmitted helminth control. Few associations with water, sanitation and hygiene were evident, despite water, sanitation and hygiene being generally poor. In our water, sanitation and hygiene we will inves
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- 2016
20. Application of a Multiplex Quantitative PCR to Assess Prevalence and Intensity Of Intestinal Parasite Infections in a Controlled Clinical Trial
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Bethony, JM, Llewellyn, S, Inpankaew, T, Nery, SV, Gray, DJ, Verweij, JJ, Clements, ACA, Gomes, SJ, Traub, R, McCarthy, JS, Bethony, JM, Llewellyn, S, Inpankaew, T, Nery, SV, Gray, DJ, Verweij, JJ, Clements, ACA, Gomes, SJ, Traub, R, and McCarthy, JS
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BACKGROUND: Accurate quantitative assessment of infection with soil transmitted helminths and protozoa is key to the interpretation of epidemiologic studies of these parasites, as well as for monitoring large scale treatment efficacy and effectiveness studies. As morbidity and transmission of helminth infections are directly related to both the prevalence and intensity of infection, there is particular need for improved techniques for assessment of infection intensity for both purposes. The current study aimed to evaluate two multiplex PCR assays to determine prevalence and intensity of intestinal parasite infections, and compare them to standard microscopy. METHODOLOGY/PRINCIPAL FINDINGS: Faecal samples were collected from a total of 680 people, originating from rural communities in Timor-Leste (467 samples) and Cambodia (213 samples). DNA was extracted from stool samples and subject to two multiplex real-time PCR reactions the first targeting: Necator americanus, Ancylostoma spp., Ascaris spp., and Trichuris trichiura; and the second Entamoeba histolytica, Cryptosporidium spp., Giardia. duodenalis, and Strongyloides stercoralis. Samples were also subject to sodium nitrate flotation for identification and quantification of STH eggs, and zinc sulphate centrifugal flotation for detection of protozoan parasites. Higher parasite prevalence was detected by multiplex PCR (hookworms 2.9 times higher, Ascaris 1.2, Giardia 1.6, along with superior polyparasitism detection with this effect magnified as the number of parasites present increased (one: 40.2% vs. 38.1%, two: 30.9% vs. 12.9%, three: 7.6% vs. 0.4%, four: 0.4% vs. 0%). Although, all STH positive samples were low intensity infections by microscopy as defined by WHO guidelines the DNA-load detected by multiplex PCR suggested higher intensity infections. CONCLUSIONS/SIGNIFICANCE: Multiplex PCR, in addition to superior sensitivity, enabled more accurate determination of infection intensity for Ascaris, hookworms and Gi
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- 2016
21. Complexities and Perplexities: A Critical Appraisal of the Evidence for Soil-Transmitted Helminth Infection-Related Morbidity
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Knopp, S, Campbell, SJ, Nery, SV, Doi, SA, Gray, DJ, Magalhaes, RJS, McCarthy, JS, Traub, RJ, Andrews, RM, Clements, ACA, Knopp, S, Campbell, SJ, Nery, SV, Doi, SA, Gray, DJ, Magalhaes, RJS, McCarthy, JS, Traub, RJ, Andrews, RM, and Clements, ACA
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BACKGROUND: Soil-transmitted helminths (STH) have acute and chronic manifestations, and can result in lifetime morbidity. Disease burden is difficult to quantify, yet quantitative evidence is required to justify large-scale deworming programmes. A recent Cochrane systematic review, which influences Global Burden of Disease (GBD) estimates for STH, has again called into question the evidence for deworming benefit on morbidity due to STH. In this narrative review, we investigate in detail what the shortfalls in evidence are. METHODOLOGY/PRINCIPAL FINDINGS: We systematically reviewed recent literature that used direct measures to investigate morbidity from STH and we critically appraised systematic reviews, particularly the most recent Cochrane systematic review investigating deworming impact on morbidity. We included six systematic reviews and meta-analyses, 36 literature reviews, 44 experimental or observational studies, and five case series. We highlight where evidence is insufficient and where research needs to be directed to strengthen morbidity evidence, ideally to prove benefits of deworming. CONCLUSIONS/SIGNIFICANCE: Overall, the Cochrane systematic review and recent studies indicate major shortfalls in evidence for direct morbidity. However, it is questionable whether the systematic review methodology should be applied to STH due to heterogeneity of the prevalence of different species in each setting. Urgent investment in studies powered to detect direct morbidity effects due to STH is required.
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- 2016
22. Water, Sanitation, and Hygiene (WASH): A Critical Component for Sustainable Soil-Transmitted Helminth and Schistosomiasis Control
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Zhou, X-N, Campbell, SJ, Savage, GB, Gray, DJ, Atkinson, J-AM, Magalhaes, RJS, Nery, SV, McCarthy, JS, Velleman, Y, Wicken, JH, Traub, RJ, Williams, GM, Andrews, RM, Clements, ACA, Zhou, X-N, Campbell, SJ, Savage, GB, Gray, DJ, Atkinson, J-AM, Magalhaes, RJS, Nery, SV, McCarthy, JS, Velleman, Y, Wicken, JH, Traub, RJ, Williams, GM, Andrews, RM, and Clements, ACA
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- 2014
23. Elemental analysis of Scottish populations of the ectoparasitic copepod Lepeophtheirus salmonis
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Shinn, Ap, James Bron, Gray, Dj, Sommerville, C., and Naturalis journals & series
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sea lice ,Copepoda ,Crustacea ,elemental analysis - Abstract
Conventional nebulisation ICPMS (Inductively Coupled Plasma Mass Spectrometry), was used to determine the concentration of a broad range of elements in the salmon louse Lepeophtheirus salmonis. Lice samples were collected from Atlantic salmon in seven localities (4 fish farms and 3 wild salmon fisheries) on two separate sampling occasions and prepared for analysis. Sixty six elements were measured, 35 of these were found to be variable and were subjected to univariate and multivariate statistical analysis. The results of the single element comparisons showed that not all individual sites could be discriminated from each other. Sea lice collected from cultured salmonids could be discriminated from those on wild salmonids at the same site using the elements magnesium (
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- 2000
24. The evolution of the DLK1-DIO3 imprinted domain in mammals
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Ponting, CP, Edwards, CA, Mungall, AJ, Matthews, L, Ryder, E, Gray, DJ, Pask, AJ, Shaw, G, Graves, JAM, Rogers, J, Dunham, I, Renfree, MB, Ferguson-Smith, AC, Ponting, CP, Edwards, CA, Mungall, AJ, Matthews, L, Ryder, E, Gray, DJ, Pask, AJ, Shaw, G, Graves, JAM, Rogers, J, Dunham, I, Renfree, MB, and Ferguson-Smith, AC
- Abstract
A comprehensive, domain-wide comparative analysis of genomic imprinting between mammals that imprint and those that do not can provide valuable information about how and why imprinting evolved. The imprinting status, DNA methylation, and genomic landscape of the Dlk1-Dio3 cluster were determined in eutherian, metatherian, and prototherian mammals including tammar wallaby and platypus. Imprinting across the whole domain evolved after the divergence of eutherian from marsupial mammals and in eutherians is under strong purifying selection. The marsupial locus at 1.6 megabases, is double that of eutherians due to the accumulation of LINE repeats. Comparative sequence analysis of the domain in seven vertebrates determined evolutionary conserved regions common to particular sub-groups and to all vertebrates. The emergence of Dlk1-Dio3 imprinting in eutherians has occurred on the maternally inherited chromosome and is associated with region-specific resistance to expansion by repetitive elements and the local introduction of noncoding transcripts including microRNAs and C/D small nucleolar RNAs. A recent mammal-specific retrotransposition event led to the formation of a completely new gene only in the eutherian domain, which may have driven imprinting at the cluster.
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- 2008
25. Assessment of platelet inhibition secondary to clopidogrel and aspirin therapy in preoperative acute surgical patients measured by Thrombelastography Platelet Mapping.
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Collyer TC, Gray DJ, Sandhu R, Berridge J, Lyons G, Collyer, T C, Gray, D J, Sandhu, R, Berridge, J, and Lyons, G
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Background: Increasing numbers of patients prescribed clopidogrel and aspirin are presenting for non-elective surgery. No consensus on the timing of surgery exists after withdrawal of antiplatelet and tests of platelet function are not routinely available. The Thrombelastography Platelet Mapping (TEG-PM) assay is designed to assess platelet inhibition secondary to antiplatelet therapy. We assessed its ability to detect platelet inhibition in preoperative acute surgical patients.Methods: We conducted a prospective observational study in three groups of preoperative patients: those taking clopidogrel or aspirin up to admission, and a control group. TEG-PM was performed on the day of admission and alternate days until surgery.Results: Mean (SD) platelet thromboxane A(2) receptor inhibition in the control group was 17.5% (23.8) (n=20), 52.6% (32.3) (n=18) in the aspirin group, and 31.9% (27.6) (n=21) in the clopidogrel group (P<0.01). Mean (SD) platelet adenosine diphosphate (ADP) receptor inhibition in the control group was 47.8% (18.9) (n=20), 52.6% (19.7) (n=18) in the aspirin group, and 71.5% (18.4) (n=21) in the clopidogrel group (P<0.01). Among the clopidogrel group awaiting surgery, mean platelet ADP channel inhibition decreased on day 3 to 67.1% (24.7) (n=11), 48.8% (24.4) (n=4) on day 5, and 36.1% (15.9) (n=2) on day 7 (P=0.57).Conclusions: TEG-PM can identify statistically significant platelet inhibition after antiplatelet therapy; however, the overlap in platelet receptor inhibition between the three groups is likely to limit the clinical usefulness of this test. [ABSTRACT FROM AUTHOR]- Published
- 2009
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26. Qualifications and quality of care
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Pereira Gray, Dj, primary
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- 1991
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27. Why are we waiting?
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Gray Dj
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Appointments and Schedules ,Text mining ,Information retrieval ,Time Factors ,business.industry ,Computer science ,MEDLINE ,General Medicine ,business - Published
- 1973
28. A randomized, double-blind, placebo-controlled trial of safety and efficacy of combined praziquantel and artemether treatment for acute schistosomiasis japonica in China.
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Hou X, McManus DP, Gray DJ, Balen J, Luo X, He Y, Ellis M, Williams GM, and Li Y
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Objective To evaluate the safety and efficacy of combining artemether (AM) and praziquantel (PZQ) in different regimens for treating acute schistosomiasis japonica. Methods We undertook a randomized, double-blind, placebo-controlled trial within four specialized schistosomiasis hospitals in the Dongting Lake region, Hunan province, China, between May 2003 and December 2005. Study participants were randomized into one of four treatment regimes: group A received 60 mg/kg PZQ + 6 mg/kg AM; group B received 60 mg/kg PZQ + AM placebo; group C received 120 mg/kg PZQ + 6 mg/kg AM; and group D received 120 mg/kg PZQ + AM placebo. All participants were followed up over a 45-day period. The primary endpoint of the trial was human infection status (determined by positive stool examination). Secondary endpoints involved clinical observations and blood biochemistry, including monitoring haemoglobin and alanine aminotransferase levels over time. Findings Treatment efficacies of the four different treatment regimens were 98.0%, 96.4%, 97.7% and 95.7% for group A, B, C, and D respectively (P > 0.05). The group B had a greater treatment efficacy (96.4%) than the group D (95.7%) (P > 0.05). Group A treatment was better for clearance of fever (P < 0.05) and resulted in a shorter hospitalization time (P < 0.05). Conclusion This is the first report of a randomized, double-blind, placebo-controlled trial for evaluating combined chemotherapy with AM and two different dosages (60 mg/kg and 120 mg/kg) of PZQ in the treatment of acute schistosomiasis japonica in China. The combination of AM and PZQ chemotherapy did not improve treatment efficacy compared with PZQ alone. PZQ given as a dosage of 60 mg/kg (1 day, 3 × 20 mg/kg doses at 4DS5 hour intervals) may be as effective as a dosage of 120 mg/kg (6 days, 20 mg/kg for each day split into 3 doses at 4DS5 hour intervals). Copyright © 2008 World Health Organization [ABSTRACT FROM AUTHOR]
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- 2008
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29. A study protocol for a multi-country cluster randomized controlled trial of the impact of a multi-component One Health strategy to eliminate Opisthorchis viverrini and soil transmitted helminths in the Lower Mekong Basin.
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Mationg ML, Clements ACA, Williams GM, Kelly M, Stewart DE, Gordon CA, Wangdi K, Tangkawattana S, Suwannatrai AT, Savathdy V, Khieu V, Wannachart S, O'Connor SY, Forsyth S, Gannon S, Odermatt P, McManus DP, Sayasone S, Khieu V, Sripa B, and Gray DJ
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- Adolescent, Adult, Animals, Child, Female, Humans, Male, Middle Aged, Young Adult, Cambodia epidemiology, Health Promotion methods, Laos, Mass Drug Administration methods, Multicenter Studies as Topic, One Health, Randomized Controlled Trials as Topic, Thailand epidemiology, Treatment Outcome, Albendazole therapeutic use, Anthelmintics therapeutic use, Helminthiasis prevention & control, Helminthiasis transmission, Helminthiasis epidemiology, Helminthiasis drug therapy, Helminthiasis parasitology, Opisthorchiasis prevention & control, Opisthorchiasis parasitology, Opisthorchiasis epidemiology, Opisthorchis, Praziquantel therapeutic use, Soil parasitology
- Abstract
Background: Opisthorchis viverrini (OV) and soil-transmitted helminths (STH) are two of the most common helminths contributing to the Neglected Tropical Disease (NTDs) burden in the Lower Mekong Basin. Although mass drug administration is the cornerstone of control programs to reduce morbidity caused by these infections, this approach has limitations in preventing re-infections. Elimination requires additional measures such as reservoir host treatment, improved hygiene and health education to reinforce MDA's impact. This study aims to examine the impact of a scalable multi-component One Health Helminth Elimination program in the Lower Mekong Basin (HELM) that combines human praziquantel (PZQ) and albendazole (ALB) treatment with a program that includes the "Magic Glasses" and the "Lawa Model" interventions with health promotion at their core., Methods: This study will employ a cluster randomized controlled trial (cRCT) in 18 rural communities (with sub-district or villages as cluster units) across Cambodia, Laos and Thailand. The control arm will receive one round of PZQ/ALB treatment, while in the intervention arm, multi-component HELM program will be implemented, which includes PZQ/ALB treatment together with the Magic Glasses and Lawa Model interventions. OV and STH infections levels will be evaluated in individuals aged 5-75 years at baseline and will be repeated at follow-up (12 months after the HELM intervention), using modified formalin ethyl-acetate concentration technique and quantitative PCR. The primary outcome of the study will be cumulative incidence of human OV and STH infections. Outcomes between the study arms will be compared using generalized linear mixed models, accounting for clustering., Discussion: Evidence from this trial will quantify the impact of a multi-component One Health control strategy in interrupting Ov and STH infections in the Lower Mekong Basin., Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12622000353796. Prospectively registered 28 February 2022., Competing Interests: Declarations. Ethics approval and consent to participate: This study was submitted to and received ethical approval from the Australian National University Human Research Ethics Committee (Protocol number 2022/507), Cambodia Ministry of Health National Ethics Committee for Health Research (NECHR) (209NECHR), the Lao PDR Ministry NECHR (07NCEHR) and Khon Kaen University Ethics Committee for Human Research (Reference No. HE651147). This study is prospectively registered with the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12622000353796. Participation in the survey will be voluntary. Informed consent will be obtained from all participants ≥ 18 years old. Inclusion of participants < 18 years old required consent from a parent or guardian and assent from individuals 5 to 17 years old. The study objectives, intervention components, voluntary participation and the right to withdraw at any time will be verbally elaborated and outlined in the information sheet. Two copies will be signed by the study participants: an original copy and a duplicate. Researchers will keep the original copies of the consents signed by the study participants and leave the duplicate copies with them for their own records. This trial will also involve collection of stool specimens for storage. If the study participants will not allow the storage and use of remaining stool samples for future research, the remaining samples will be disposed immediately after the completion of all the procedures of this study. This study also obtained ethical approval from the Australian National University Animal Ethics Committee (Protocol Number A2022/27) and Institutional Animal Care and Use Committee of Khon Kaen University (Reference No. 660201.2.11/245 (39)). Consent for publication: Not applicable—there are no personal information or identifying images of study participants are presented here or will be presented in reports of the trial results. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)
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- 2024
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30. Examining the Acceptability of Helminth Education Packages "Magic Glasses Lower Mekong" and "Magic Glasses Opisthorchiasis" and Their Impact on Knowledge, Attitudes, and Practices Among Schoolchildren in the Lower Mekong Basin: Protocol for a Cluster Randomized Controlled Trial.
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O'Connor SY, Mationg ML, Kelly MJ, Williams GM, Clements AC, Sripa B, Sayasone S, Khieu V, Wangdi K, Stewart DE, Tangkawattana S, Suwannatrai AT, Savathdy V, Khieu V, Odermatt P, Gordon CA, Wannachart S, McManus DP, and Gray DJ
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- Humans, Child, Cambodia epidemiology, Laos epidemiology, Thailand epidemiology, Female, Male, Adolescent, Students psychology, Helminthiasis prevention & control, Helminthiasis epidemiology, Animals, Cartoons as Topic, Health Knowledge, Attitudes, Practice, Opisthorchiasis prevention & control, Opisthorchiasis epidemiology, Opisthorchiasis psychology, Health Education methods
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Background: Helminths are a major global health issue, impacting health, educational, and socioeconomic outcomes. Infections, often starting in childhood, are linked to anemia, malnutrition, cognitive deficit, and in chronic cases of Opisthorchis viverrini (OV), cholangiocarcinoma. The main control strategy for helminth infection is mass drug administration; however, this does not prevent reinfection. As such, prevention strategies are needed. The "Magic Glasses" is a school-based cartoon health education package that has demonstrated success in improving knowledge, attitudes, and practices (KAP) surrounding soil-transmitted helminths (STH) in China and the Philippines. This study is designed to assess the acceptability and impact of the 2 new versions of the Magic Glasses targeting STH and OV designed for the Lower Mekong audience in Cambodia, Lao People's Democratic Republic (PDR), and Thailand., Objective: The objective of this study is to evaluate the acceptability of the "Magic Glasses Lower Mekong" and "Magic Glasses Opisthorchiasis" education packages among schoolchildren in the Lower Mekong Basin, and the impact of these education packages on students' KAP surrounding STH and OV, respectively., Methods: Schoolchildren will be recruited into a cluster randomized controlled trial with intervention and control arms in rural schools in Cambodia, Lao PDR, and Thailand. Schoolchildren's initial acceptability of the intervention will be evaluated using an adapted questionnaire. Sustained acceptability will be assessed at 9-month follow-up through focus group discussions with students and interviews with teachers. Impact will be evaluated by KAP questionnaires on STH and OV. KAP questionnaires will be administered to children at baseline and at follow-up. Indirect impact on parents' KAP of OV and STH will be assessed through focus group discussions at follow-up., Results: The trial is in progress in Lao PDR and Thailand and is expected to commence in Cambodia in January 2024. The results of the study are expected to be available 18 months from the start of recruitment. We hypothesize that participants enrolled in the intervention arm of the study will have higher KAP scores for STH and OV, compared with the participants in the control arm at follow-up. We expect that students will have initial and sustained acceptability of these intervention packages., Conclusions: This trial will examine the acceptability of the "Magic Glasses Opisthorchiasis" and "Magic Glasses Lower Mekong" interventions and provide evidence on the effectiveness of the "Magic Glasses" on KAP related to OV and STH among schoolchildren in the Lower Mekong Basin. Study results will provide insight on acceptability and impact indicators and inform a scaling up protocol for the "Magic Glasses" education packages in Cambodia, Lao PDR, and Thailand., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12623000271606; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385315&isReview=true., International Registered Report Identifier (irrid): DERR1-10.2196/55290., (©Suji Y O'Connor, Mary Lorraine Mationg, Matthew J Kelly, Gail M Williams, Archie CA Clements, Banchob Sripa, Somphou Sayasone, Virak Khieu, Kinley Wangdi, Donald E Stewart, Sirikachorn Tangkawattana, Apiporn T Suwannatrai, Vanthanom Savathdy, Visal Khieu, Peter Odermatt, Catherine A Gordon, Sangduan Wannachart, Donald P McManus, Darren J Gray. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 16.09.2024.)
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- 2024
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31. Prevalence and determinants of hypertension in South-Asian Urban Communities: findings from Demographic and Health Surveys (DHS) data of South Asian countries.
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Talukder A, Sara SS, Khan ZI, Yadav UN, Mistry SK, Biswas T, Alam A, Ali MW, Jannat Z, Haseen F, Uddin MJ, Gray DJ, Ahmed T, Kelly M, Islam SMS, and Sarma H
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- Female, Humans, Prevalence, Obesity epidemiology, Risk Factors, India epidemiology, Health Surveys, Socioeconomic Factors, Caffeine, Hypertension diagnosis, Hypertension epidemiology
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Hypertension increases risk of stroke and other cardiovascular diseases, however, its prevalence and determinants in South Asian urban communities using country representative community-based datasets is lacking. This study evaluated prevalence of hypertension and it's determinants among urban residents of three South Asian countries. Urban population data from demographic and health surveys in Bangladesh, India, and Nepal were extracted. Hypertension prevalence was defined as systolic/diastolic blood pressure ≥ 140/ 90 mmHg. Age, education, wealth, physical activity, alcohol, BMI were considered as risk factors associated with the increased risk of hypertension. We performed binary logistic regression and calculated adjusted Odds Ratios (AOR) with 95% confidence interval (CI) to assess factors related to hypertension. Hypertension prevalence was 37.4% in India, 25.1% in Bangladesh and 18.4% in Nepal. Prevalence increased with age in all settings. Females had reduced odds of hypertension in Bangladesh (AOR 0.75; CI: 0.69, 0.81) and Nepal (AOR 0.62; CI: 0.54, 0.71), but higher risk in India (AOR 2.54; CI: 2.45, 2.63). Low education, caffeine consumption, obesity was associated with higher prevalence of hypertension in all three countries. Smokers had increased odds of hypertension in India (AOR 1.11; CI: 1.06, 1.15) and Nepal (AOR 1.23; 1.02, 1.47). Overall, hypertension prevalence is high in all three countries. Modifiable socioeconomic and lifestyle factors (education, wealth index, smoking status, caffeine consumption and BMI) associated with hypertension. Comprehensive hypertension pacific and sensitive interventions (including behavioral modification treatments and timely screening and access to health care) are urgently needed to prevent and control hypertension among urban populations in South Asia., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2024
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32. Serological Comparison of Native Antigen ELISAs with Rapid ICT Test Kits for the Diagnosis of Human Alveolar and Cystic Echinococcosis in China.
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Yang SK, Zhang W, Zhu N, McManus DP, Gray DJ, Clements ACA, Cadavid Restrepo AM, Williams GM, Zhang T, Ma GR, Yang YH, and Yang YR
- Abstract
Background: The aim of this study was to compare the diagnostic performance of native antigen ELISAs and ADAMU-AE/CE commercial ICT test kits in subjects either exposed to Echinococcus infection or with clinically diagnosed alveolar (AE) or cystic (CE) echinococcosis., Methods: A total of 370 subjects with a previous clinical confirmation of CE or AE from northwestern China were recruited. Serum samples were also obtained from 3923 children/teenagers during a community survey. All sera were tested using native antigen ELISAs. The ADAMU-AE/CE test kits were subsequently used for the serology of the 370 clinically confirmed individuals and of 251 children/teenagers that were ELISA antibody-positive for both Echinococcus species but ultrasound-negative during baseline survey. An analysis of the association between the serological tests and ultrasound classification was carried out amongst 89 AE and 164 CE cases. A Kappa consistency analysis was undertaken to compare the diagnostic performance of the native antigen ELISAs and the ADAMU kits and the ultrasound imaging results. The χ² test was also used for a comparison of the different seropositivity rates between the groups., Findings: There was poor consistency (Kappa = 0.26 and 0.28 for AE and CE respectively) between the native antigen ELISAs and the ADAMU kits for the diagnosis of AE and CE among the cases and the surveyed children/teenagers, but a relatively good consistency (Kappa = 0.63) between the ADAMU-AE kit and ultrasound observations for the AE cases. Additionally, of the 251 teenagers co-positive for both AE and CE antibodies by the native antigen ELISAs, only one was found positive by the ADAMU-AE kit, verified as a new AE case on subsequent ultrasound follow-up. The remainder (N = 250) were negative by serology using the ADAMU-AE/CE kits and by ultrasound examination. The two native antigen ELISAs did not discriminate well between cases of clinically diagnosed AE and CE. In contrast, ADAMU-AE and ADAMU-CE commercial ICT test kits readily differentiated cases of AE from CE with specificities of 99% for AE and 100% for CE., Conclusions: The ADAMU-AE/CE kits proved reliable, accurate, and amenable diagnostic tools in the clinical setting for confirmation of suspected AE/CE cases. The native antigen ELISAs tests can provide useful information on the level of human exposure to Echinococcus infection.
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- 2024
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33. Transmission-Blocking Vaccines against Schistosomiasis Japonica.
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Zumuk CP, Jones MK, Navarro S, Gray DJ, and You H
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- Animals, Female, Cattle, Humans, Vaccination, China epidemiology, Buffaloes, Schistosomiasis japonica prevention & control, Schistosomiasis japonica veterinary, Schistosoma japonicum, Vaccines, Schistosomiasis
- Abstract
Control of schistosomiasis japonica, endemic in Asia, including the Philippines, China, and Indonesia, is extremely challenging. Schistosoma japonicum is a highly pathogenic helminth parasite, with disease arising predominantly from an immune reaction to entrapped parasite eggs in tissues. Females of this species can generate 1000-2200 eggs per day, which is about 3- to 15-fold greater than the egg output of other schistosome species. Bovines (water buffalo and cattle) are the predominant definitive hosts and are estimated to generate up to 90% of parasite eggs released into the environment in rural endemic areas where these hosts and humans are present. Here, we highlight the necessity of developing veterinary transmission-blocking vaccines for bovines to better control the disease and review potential vaccine candidates. We also point out that the approach to producing efficacious transmission-blocking animal-based vaccines before moving on to human vaccines is crucial. This will result in effective and feasible public health outcomes in agreement with the One Health concept to achieve optimum health for people, animals, and the environment. Indeed, incorporating a veterinary-based transmission vaccine, coupled with interventions such as human mass drug administration, improved sanitation and hygiene, health education, and snail control, would be invaluable to eliminating zoonotic schistosomiasis.
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- 2024
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34. Strongyloidiasis.
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Gordon CA, Utzinger J, Muhi S, Becker SL, Keiser J, Khieu V, and Gray DJ
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- Animals, Female, Humans, Ivermectin therapeutic use, Immunocompromised Host, Feces parasitology, Strongyloidiasis diagnosis, Strongyloidiasis epidemiology, Strongyloidiasis drug therapy, Strongyloides stercoralis
- Abstract
Strongyloidiasis is a neglected tropical disease caused primarily by the roundworm Strongyloides stercoralis. Strongyloidiasis is most prevalent in Southeast Asia and the Western Pacific. Although cases have been documented worldwide, global prevalence is largely unknown due to limited surveillance. Infection of the definitive human host occurs via direct skin penetration of the infective filariform larvae. Parasitic females reside in the small intestine and reproduce via parthenogenesis, where eggs hatch inside the host before rhabditiform larvae are excreted in faeces to begin the single generation free-living life cycle. Rhabditiform larvae can also develop directly into infectious filariform larvae in the gut and cause autoinfection. Although many are asymptomatic, infected individuals may report a range of non-specific gastrointestinal, respiratory or skin symptoms. Autoinfection may cause hyperinfection and disseminated strongyloidiasis in immunocompromised individuals, which is often fatal. Diagnosis requires direct examination of larvae in clinical specimens, positive serology or nucleic acid detection. However, there is a lack of standardization of techniques for all diagnostic types. Ivermectin is the treatment of choice. Control and elimination of strongyloidiasis will require a multifaceted, integrated approach, including highly sensitive and standardized diagnostics, active surveillance, health information, education and communication strategies, improved water, sanitation and hygiene, access to efficacious treatment, vaccine development and better integration and acknowledgement in current helminth control programmes., (© 2024. Springer Nature Limited.)
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- 2024
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35. A review of health education activities targeting schoolchildren for the control of soil-transmitted helminthiasis in Southeast Asia, with emphasis upon the Magic Glasses approach.
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Mationg MLS, Williams GM, Tallo VL, Olveda RM, McManus DP, Stewart DE, and Gray DJ
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- Child, Humans, Public Health, China, Asia, Southeastern epidemiology, Health Education, Helminthiasis drug therapy, Helminthiasis epidemiology, Helminthiasis prevention & control
- Abstract
Soil-transmitted helminths continue to be a serious problem causing disease and morbidity globally. Children, mostly school-aged, are more at risk of these infections. The main strategy for control remains to be the mass drug administration (MDA) of antihelminthic drugs. With the limitation of MDA to prevent re-infection, the need for additional approaches such as hygiene education and improvements in water, sanitation and hygiene (WASH) infrastructure are required. Although the importance of health education as a crucial component of an integrated approaches to STH control is highlighted, this component has often been disregarded because the other more complex solutions have been the focus of most studies and programmes. We performed literature searches from four bibliographic databases - Scopus, PubMed, Web of Science and Cochrane Library - to determine availability of studies on the impact of health education interventions targeting STH infections on schoolchildren in Southeast Asia. Our review found only three studies that evaluated health education interventions targeting children. The current lack of evidence in this area suggests the need for more studies assessing the impact of health education intervention for STH control. A successful health education programme for STH called "The Magic Glasses" has been developed targeting schoolchildren in China and the Philippines. This public health intervention displayed significant impact in terms of improving knowledge, attitude and practices, reducing prevalence of STH infections in schoolchildren and encouraging compliance to MDA. This article details the successes and benefits of the Magic Glasses programme as a promising control tool for STH in the Southeast Asian region., (Copyright © 2024. Published by Elsevier Ltd.)
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- 2024
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36. Risk mapping and socio-ecological drivers of soil-transmitted helminth infections in the Philippines: a spatial modelling study.
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Tsheten T, Alene KA, Restrepo AC, Kelly M, Lau C, Clements ACA, Gray DJ, Daga C, Mapalo VJ, Espino FE, and Wangdi K
- Abstract
Background: The Philippines reports a high prevalence of soil-transmitted helminth (STH) infections despite the implementation of nationwide mass drug administration since 2006. The spatial variation of STH infections in the Philippines was last described using the 2005-2007 national STH and schistosomiasis survey. This study aimed to identify sociodemographic and environmental factors that drive STH transmission and predict high-risk areas in the Philippines., Methods: Epidemiological data on STH for students aged 5-16 years were obtained from the 2015 Philippines National Prevalence survey, while environmental data were extracted from satellite images and publicly available sources. Model-based geostatistics, implemented in a Bayesian framework, was used to identify sociodemographic and environmental correlates and predict high-risk areas for STH across the Philippines. The best-fitting model with the lowest deviance information criterion (DIC) was used to interpret the findings of the model and predict STH infection risk for the entire country. Risk maps were developed for each STH infection using the posterior means derived from the model., Findings: The prevalence of Ascaris lumbricoides (20.0%) and Trichuris trichiura (29.3%) was higher in the Visayas Island than in the Luzon and Mindanao Islands. Hookworm prevalence was highest in Mindanao Island (1.3%). Risk of A. lumbricoides was positively associated with males (odds ratio [OR]: 1.197; 97.5% Credible Interval [CrI]: 1.114, 1.286) and temperature (OR: 1.148; 97.5% CrI: 1.033, 1.291), while normalized difference vegetation index (OR: 0.354; 97.5% CrI: 0.138, 0.930) and soil pH (OR: 0.606; 97.5% CrI: 0.338, 0.949) were negatively associated with the transmission. T. trichiura risk was positively associated with males (OR: 1.261; 97.5% CrI: 1.173, 1.341), temperature (OR: 1.153; 97.5% CrI: 1.001, 1.301), and rainfall (OR: 1.004; 97.5% CrI: 1.011, 1.069). Hookworm risk was positively associated with males (OR: 2.142; 97.5% CrI: 1.537, 2.998), while children aged ≤12 years (OR: 0.435; 97.5% CrI: 0.252, 0.753) had a negative association with risk compared to those over 12 years. Focal areas of high risk were identified for A. lumbricoides and T. trichiura in the Visayas Island, and hookworm in the Mindanao Island., Interpretation: The spatial distribution of all three STH infections has considerably decreased since a previous national risk-mapping exercise. The high-risk areas identified in the study can be used to strategically target deworming and health education activities to further reduce the burden of STH and support progress toward elimination., Funding: The Australian Centre for the Control and Elimination of Neglected Tropical Diseases and the Australian National Health and Medical Research Council., Competing Interests: Authors have nothing to declare., (© 2023 The Authors.)
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- 2023
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37. Community-wide versus school-based targeted deworming for soil-transmitted helminth control in school-aged children in Vietnam: the CoDe-STH cluster-randomised controlled trial.
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Dyer CEF, Ng-Nguyen D, Clarke NE, Hii SF, Nguyen HQ, Nguyen VT, Nguyen TV, Nguyen TV, Ngo TT, Herath HMPD, Wand H, Coffeng LE, Marshall JC, Gray DJ, Anderson RM, Clements ACA, Kaldor JM, Traub RJ, and Vaz Nery S
- Abstract
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 showed greater relative reduction in prevalence of moderate-to-heavy intensity (≥2000 EPG) N. americanus infections (81.1%; 95% CI 69.7-92.6) compared to the school arm (39.0%, 95% CI 13.7-64.2)., Interpretation: Although no impact was seen on overall prevalence, community-wide MDA was more effective in lowering N. americanus infection intensity in schoolchildren compared to school-based targeted PC, measured 12 months after one round of albendazole deworming with high coverage., Funding: National Health and Medical Research Council, Australia (APP1139561)., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)
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- 2023
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38. Photoactivatable Agonist-Antagonist Pair as a Tool for Precise Spatiotemporal Control of Serotonin Receptor 2C Signaling.
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Kim ST, Doukmak EJ, Shanguhyia M, Gray DJ, and Steinhardt RC
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- Serotonin Receptor Agonists, Serotonin 5-HT2 Receptor Agonists pharmacology, Serotonin metabolism, Receptor, Serotonin, 5-HT2C
- Abstract
Orthogonal recreation of the signaling profile of a chemical synapse is a current challenge in neuroscience. This is due in part to the kinetics of synaptic signaling, where neurotransmitters are rapidly released and quickly cleared by active reuptake machinery. One strategy to produce a rapid rise in an orthogonally controlled signal is via photocaged compounds. In this work, photocaged compounds are employed to recreate both the rapid rise and equally rapid fall in activation at a chemical synapse. Specifically, a complementary pair of photocages based on BODIPY were conjugated to a 5-HT
2C subtype-selective agonist, WAY-161503, and antagonist, N -desmethylclozapine, to generate "caged" versions of these drugs. These conjugates release the bioactive drug upon illumination with green light (agonist) or red light (antagonist). We report on the synthesis, characterization, and bioactivity testing of the conjugates against the 5-HT2C receptor. We then characterize the kinetics of photolysis quantitatively using HPLC and qualitatively in cell culture conditions stimulating live cells. The compounds are shown to be stable in the dark for 48 h at room temperature, yet photolyze rapidly when irradiated with visible light. In live cells expressing the 5-HT2C receptor, precise spatiotemporal control of the degree and length of calcium signaling is demonstrated. By loading both compounds in tandem and leveraging spectral multiplexing as a noninvasive method to control local small-molecule drug availability, we can reproducibly initiate and suppress intracellular calcium flux on a timescale not possible by traditional methods of drug dosing. These tools enable a greater spatiotemporal control of 5-HT2C modulation and will allow for more detailed studies of the receptors' signaling, interactions with other proteins, and native physiology.- Published
- 2023
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39. Epidemiology of soil-transmitted helminths using quantitative PCR and risk factors for hookworm and Necator americanus infection in school children in Dak Lak province, Vietnam.
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Hughes A, Ng-Nguyen D, Clarke NE, Dyer CEF, Hii SF, Clements ACA, Anderson RM, Gray DJ, Coffeng LE, Kaldor JM, Traub RJ, and Vaz Nery S
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- Animals, Humans, Child, Female, Necator americanus genetics, Ancylostomatoidea genetics, Soil parasitology, Cross-Sectional Studies, Vietnam epidemiology, Ethnicity, Minority Groups, Polymerase Chain Reaction, Schools, Risk Factors, Prevalence, Water parasitology, Feces parasitology, Helminths, Helminthiasis, Hookworm Infections epidemiology
- Abstract
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 infections conducted using qPCR as a diagnostic technique. The findings of higher adjusted odds of infection amongst ethnic minority children highlight that STH control programmes may not be reaching certain population groups and that additional culturally appropriate approaches may be required. Additionally, the associations between specific WASH factors and infection indicate potential programmatic targets to complement preventive chemotherapy programmes., (© 2023. The Author(s).)
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- 2023
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40. Impact of COVID-19 on mental health in Bhutan: a way forward for action.
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Tsheten T, Chateau D, Dorji N, Pokhrel HP, Clements ACA, Gray DJ, and Wangdi K
- Abstract
The coronavirus disease 2019 (COVID-19) pandemic continues to impact mental health and wellbeing globally. There is a lack of scientific documentation highlighting the mental health impact of COVID-19 in Bhutan. We present the mental health burdens and control measures taken, and suggest ways to further strengthen mental health services in Bhutan. During the pandemic, a rise in depression and anxiety had been reported in Bhutan. Depression rose from an average prevalence of 9 per 10,000 between 2011 and 2019 to 16 per 10,000 in 2020 and 32 per 10,000 in 2021. Similarly, anxiety rose from an average prevalence of 18 per 10,000, to 29 per 10,000 in 2020, and 55 per 10,000 in 2021. Psychological impacts related to isolation due to lockdowns, economic losses, and poor coping abilities were associated with negative outcomes. Stigma and discrimination towards mental health disorders discouraged mentally distressed people from seeking care. In response to increased demand, Bhutan's government initiated a range of interventions including home delivery of medicines and tele-counselling to people in need of urgent mental health care. Mental health care in Bhutan can be further improved through investment in services and human resources, and decentralization of services to the community., Competing Interests: We declare no competing interests., (© 2023 The Author(s).)
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- 2023
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41. First bovine vaccine to prevent human schistosomiasis - a cluster randomised Phase 3 clinical trial.
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Ross AG, Harn DA, Chy D, Inobaya M, Guevarra JR, Shollenberger L, Li Y, McManus DP, Gray DJ, and Williams GM
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- Animals, Humans, Cattle, Australia, China, Snails parasitology, Schistosomiasis japonica epidemiology, Schistosomiasis japonica prevention & control, Schistosomiasis japonica veterinary, Schistosomiasis epidemiology, Schistosomiasis prevention & control, Schistosoma japonicum, Vaccines
- Abstract
Objective: Schistosomiasis is a neglected tropical parasitic disease caused by blood flukes of the genus Schistosoma. Schistosoma japonicum is zoonotic in China, the Philippines, and Indonesia, with bovines acting as major reservoirs of human infection. The primary objective of the trial was to examine the impact of a combination of human mass chemotherapy, snail control through mollusciciding, and SjCTPI bovine vaccination on the rate of human infection., Methods: A 5-year phase IIIa cluster randomized control trial was conducted among 18 schistosomiasis-endemic villages comprising 18,221 residents in Northern Samar, The Philippines., Results: Overall, bovine vaccination resulted in a statistically significant decrease in human infection (relative risk [RR] = 0.75; 95% confidence interval [CI] = 0.69 to 0.82) across all trial follow-ups. The best outcome of the trial was when bovine vaccination was combined with snail mollusciciding. This combination resulted in a 31% reduction (RR = 0.69; 95% CI = 0.61 to 0.78) in human infection., Conclusion: This is the first trial to demonstrate the effectiveness of a bovine vaccine for schistosomiasis in reducing human schistosome infection. The trial is registered with Australian New Zealand Clinical Trials Registry (ACTRN12619001048178)., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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42. Model validation for a knowledge and practices survey towards prevention of soil-transmitted helminth infections in rural villages in Indonesia.
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Lee P, Kurscheid JM, Laksono B, Park MJ, Clements ACA, Lowe C, Stewart DE, and Gray DJ
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- Child, Adult, Humans, Animals, Soil, Indonesia epidemiology, Cross-Sectional Studies, Surveys and Questionnaires, Prevalence, Feces, Helminthiasis epidemiology, Helminthiasis prevention & control, Helminths
- Abstract
The rate of soil-transmitted helminth (STH) infection is estimated to be around 20% in Indonesia. Health promotion and health education are cost-effective strategies to supplement STH prevention and control programs. Existing studies suggest that quantitative tools for knowledge, attitudes and practices (KAP) are important to monitor effective community-based STH interventions. However, evidence is limited regarding the applicability of such tools. This study aims to identify the socio-demographic predictors for STH-related knowledge and practices and validate the quantitative tools in population use. A cross-sectional study design was conducted among residents of 16 villages in Central Java, Indonesia. Adult and child respondents were interviewed to assess general knowledge and practices in relation to STH. Two mixed effects models identified the significant factors in predicting knowledge and practice scores. The model predicted knowledge and practice scores were compared with the observed scores to validate the quantitative measurements developed in this study. Participants' socio-demographic variables were significant in predicting an individual's STH-related knowledge level and their hand washing and hygiene practices, taking into account household-level variability. Model validation results confirmed that the quantitative measurement tools were suitable for assessing STH associated knowledge and behaviour. The questionnaire developed in this study can be used to support school- and community-based health education interventions to maximize the effect of STH prevention and control programs., (© 2023. The Author(s).)
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- 2023
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43. Developing Photoaffinity Probes for Dopamine Receptor D 2 to Determine Targets of Parkinson's Disease Drugs.
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Kim ST, Doukmak EJ, Flax RG, Gray DJ, Zirimu VN, de Jong E, and Steinhardt RC
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- Animals, Rats, Nitric Oxide Synthase Type I metabolism, Ligands, Proteomics, Endocannabinoids, Receptors, Dopamine D1, Carrier Proteins, Receptors, GABA metabolism, Dopamine Agonists pharmacology, Receptors, Dopamine D2 metabolism, Parkinson Disease drug therapy
- Abstract
Dopaminergic pathways control highly consequential aspects of physiology and behavior. One of the most therapeutically important and best-studied receptors in these pathways is dopamine receptor D
2 (DRD2). Unfortunately, DRD2 is challenging to study with traditional molecular biological techniques, and most drugs designed to target DRD2 are ligands for many other receptors. Here, we developed probes able to both covalently bind to DRD2 using photoaffinity labeling and provide a chemical handle for detection or affinity purification. These probes behaved like good DRD2 agonists in traditional biochemical assays and were able to perform in chemical-biological assays of cell and receptor labeling. Rat whole brain labeling and affinity enrichment using the probes permitted proteomic analysis of the probes' interacting proteins. Bioinformatic study of the hits revealed that the probes bound noncanonically targeted proteins in Parkinson's disease network as well as the retrograde endocannabinoid signaling, neuronal nitric oxide synthase, muscarinic acetylcholine receptor M1, GABA receptor, and dopamine receptor D1 (DRD1) signaling networks. Follow-up analysis may yield insights into how this pathway relates specifically to Parkinson's disease symptoms or provide new targets for treatments. This work reinforces the notion that the combination of chemical biology and omics-based approaches provides a broad picture of a molecule's "interactome" and may also give insight into the pleiotropy of effects observed for a drug or perhaps indicate new applications.- Published
- 2022
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44. Spatial Analysis of Schistosomiasis in Hunan and Jiangxi Provinces in the People's Republic of China.
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Alene KA, Gordon CA, Clements ACA, Williams GM, Gray DJ, Zhou XN, Li Y, Utzinger J, Kurscheid J, Forsyth S, Zhou J, Li Z, Li G, Lin D, Lou Z, Li S, Ge J, Xu J, Yu X, Hu F, Xie S, and McManus DP
- Abstract
Understanding the spatial distribution of schistosome infection is critical for tailoring preventive measures to control and eliminate schistosomiasis. This study used spatial analysis to determine risk factors that may impact Schistosoma japonicum infection and predict risk in Hunan and Jiangxi Provinces in the People's Republic of China. The study employed survey data collected in Hunan and Jiangxi in 2016. Independent variable data were obtained from publicly available sources. Bayesian-based geostatistics was used to build models with covariate fixed effects and spatial random effects to identify factors associated with the spatial distribution of infection. Prevalence of schistosomiasis was higher in Hunan (12.8%) than Jiangxi (2.6%). Spatial distribution of schistosomiasis varied at pixel level (0.1 × 0.1 km), and was significantly associated with distance to nearest waterbody (km, β = -1.158; 95% credible interval [CrI]: -2.104, -0.116) in Hunan and temperature (°C, β = -4.359; 95% CrI: -9.641, -0.055) in Jiangxi. The spatial distribution of schistosomiasis in Hunan and Jiangxi varied substantially and was significantly associated with distance to nearest waterbody. Prevalence of schistosomiasis decreased with increasing distance to nearest waterbody in Hunan, indicating that schistosomiasis control should target individuals in close proximity to open water sources as they are at highest risk of infection.
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- 2022
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45. Cost analysis for "The Magic Glasses Philippines" health education package to prevent intestinal worm infections among Filipino schoolchildren.
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Mationg MLS, Williams GM, Tallo VL, Olveda RM, Aung E, Alday P, Reñosa MD, Daga CM, Landicho J, Demonteverde MP, Santos ED, Bravo TA, Bourke S, Munira SL, Bieri FA, Li YS, Clements ACA, Steinmann P, Halton K, Stewart DE, McManus DP, and Gray DJ
- Abstract
Background: Soil-transmitted helminth (STH) infections are a significant public health problem affecting over 900 million people globally. Health education has been shown to complement mass drug administration (MDA) for the control of these intestinal worms. We reported recently results of a cluster randomised control trial (RCT) showing the positive impact of the "The Magic Glasses Philippines (MGP)" health education package in reducing STH infections among schoolchildren in intervention schools with ≤15% STH baseline prevalence in Laguna province, the Philippines. To inform decision making on the economic implications of the MGP, we evaluated the in-trial costs and then quantified the costs of scaling up the intervention both regionally and nationally., Methods: Costs were determined for the MGP RCT conducted in 40 schools in Laguna province. We estimated the total cost and the costs incurred per student for the actual RCT and the total costs for regional and national scale-up in all schools regardless of STH endemicity. The costs associated with the implementation of standard health education (SHE) activities and mass drug administration (MDA) were determined with a public sector perspective., Findings: The cost per participating student in the MGP RCT was Php 58.65 (USD 1.15) but if teachers instead of research staff had been involved, the estimated cost would have been considerably lower at Php 39.45 (USD 0.77). Extrapolating the costs for regional scale-up, the costs per student were estimated to be Php 15.24 (USD 0.30). As it is scaled up at the national level to include more schoolchildren, the estimated cost was increased at Php 17.46 (USD 0.34). In scenario 2 and 3, consistently, labour/salary costs associated with the delivery of the MGP contributed most to overall programme expenditure. Furthermore, the estimated average cost per student for SHE and MDA were Php 117.34 (USD 2.30) and Php 58.17 (USD 1.14), respectively. Using national scale up estimates, the cost of combining the MGP with SHE and MDA was Php 192.97 (USD 3.79)., Interpretation: These findings suggest that the integration of MGP into the school curriculum would be an affordable and scalable approach to respond to the continuous burden of STH infection among schoolchildren in the Philippines., Funding: National and Medical Research Council, Australia, and the UBS-Optimus Foundation, Switzerland., Competing Interests: All authors declare no competing interests., (© 2022 The Author(s).)
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- 2022
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46. Identifying socio-ecological drivers of common cold in Bhutan: a national surveillance data analysis.
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Tsheten T, Penjor K, Tshering C, Clements ACA, Gray DJ, and Wangdi K
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- Adult, Bayes Theorem, Bhutan epidemiology, Child, Data Analysis, Female, Humans, Incidence, Male, Spatio-Temporal Analysis, Common Cold epidemiology
- Abstract
The common cold is a leading cause of morbidity and contributes significantly to the health costs in Bhutan. The study utilized multivariate Zero-inflated Poisson regression in a Bayesian framework to identify climatic variability and spatial and temporal patterns of the common cold in Bhutan. There were 2,480,509 notifications of common cold between 2010 and 2018. Children aged < 15 years were twice (95% credible interval [CrI] 2.2, 2.5) as likely to get common cold than adults, and males were 12.4% (95 CrI 5.5%, 18.7%) less likely to get common cold than females. A 10 mm increase in rainfall lagged one month, and each 1 °C increase of maximum temperature was associated with a 5.1% (95% CrI 4.2%, 6.1%) and 2.6% (95% CrI 2.3%, 2.8%) increase in the risk of cold respectively. An increase in elevation of 100 m and 1% increase in relative humidity lagged three months were associated with a decrease in risk of common cold by 0.1% (95% CrI 0.1%, 0.2%) and 0.3% (95% CrI 0.2%, 0.3%) respectively. Seasonality and spatial heterogeneity can partly be explained by the association of common cold to climatic variables. There was statistically significant residual clustering after accounting for covariates. The finding highlights the influence of climatic variables on common cold and suggests that prioritizing control strategies for acute respiratory infection program to subdistricts and times of the year when climatic variables are associated with common cold may be an effective strategy., (© 2022. The Author(s).)
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- 2022
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47. High prevalence of soil-transmitted helminth infections in Myanmar schoolchildren.
- Author
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Aung E, Han KT, Gordon CA, Hlaing NN, Aye MM, Htun MW, Wai KT, Myat SM, Thwe TL, Tun A, Wangdi K, Li Y, Williams GM, Clements ACA, Vaz Nery S, McManus DP, and Gray DJ
- Subjects
- Animals, Child, Cross-Sectional Studies, Humans, Myanmar epidemiology, Prevalence, Ascaris lumbricoides, Soil
- Abstract
Background: Achieving the elimination of soil-transmitted helminth (STH) infections requires a sufficient understanding of the current epidemiological status of STH endemicity. We aimed to examine the status of STH in Myanmar - a country with the eighth highest STH prevalence in the world, 10 years after instigation of the national deworming programme., Methods: In August 2016 we screened for STH infections using Kato Katz (KK) microscopy and real-time PCR (qPCR) in schoolchildren from the Bago Region township of Phyu, a STH sentinel site in Myanmar. Ten schools were randomly selected, and one stool sample each from a total of 264 students was examined. Prevalence and intensity of infection were calculated for each STH., Results: High prevalence of STH was identified in the study area with 78.8% of the schoolchildren infected with at least one STH by qPCR, and 33.3% by KK. The most prevalent STH was Trichuris trichiura, diagnosed by both KK (26.1%) and qPCR (67.1%), followed by Ascaris lumbricoides (15.5% KK; 54.9% qPCR). No hookworm infections were identified by KK; however, the qPCR analysis showed a high prevalence of Ancylostoma sp. infection (29.6%) with few Necator americanus (1.1%) infections., Conclusions: Despite bi-annual deworming of schoolchildren in the fourth-grade and below, STH prevalence remains stubbornly high. These results informed the expansion of the Myanmar National STH control programme to include all school-aged children by the Ministry of Health and Sports in 2017, however further expansion to the whole community should be considered along with improving sanitation and hygiene measures. This would be augmented by rigorous monitoring and evaluation, including national prevalence surveys., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
48. Schistosomiasis in the People's Republic of China - down but not out.
- Author
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Gordon CA, Williams GM, Gray DJ, Clements ACA, Zhou XN, Li Y, Utzinger J, Kurscheid J, Forsyth S, Addis Alene K, Zhou J, Li Z, Li G, Lin D, Lou Z, Li S, Ge J, Xu J, Yu X, Hu F, Xie S, Chen J, Shi T, Li C, Zheng H, and McManus DP
- Subjects
- Animals, Cattle, China epidemiology, Humans, Longitudinal Studies, Prevalence, Real-Time Polymerase Chain Reaction, Snails, Schistosoma japonicum genetics, Schistosomiasis epidemiology, Schistosomiasis japonica epidemiology, Schistosomiasis japonica veterinary
- Abstract
Schistosomiasis has been subjected to extensive control efforts in the People's Republic of China (China) which aims to eliminate the disease by 2030. We describe baseline results of a longitudinal cohort study undertaken in the Dongting and Poyang lakes areas of central China designed to determine the prevalence of Schistosoma japonicum in humans, animals (goats and bovines) and Oncomelania snails utilizing molecular diagnostics procedures. Data from the Chinese National Schistosomiasis Control Programme (CNSCP) were compared with the molecular results obtained.Sixteen villages from Hunan and Jiangxi provinces were surveyed; animals were only found in Hunan. The prevalence of schistosomiasis in humans was 1.8% in Jiangxi and 8.0% in Hunan determined by real-time polymerase chain reaction (PCR), while 18.3% of animals were positive by digital droplet PCR. The CNSCP data indicated that all villages harboured S. japonicum-infected individuals, detected serologically by indirect haemagglutination assay (IHA), but very few, if any, of these were subsequently positive by Kato-Katz (KK).Based on the outcome of the IHA and KK results, the CNSCP incorporates targeted human praziquantel chemotherapy but this approach can miss some infections as evidenced by the results reported here. Sensitive molecular diagnostics can play a key role in the elimination of schistosomiasis in China and inform control measures allowing for a more systematic approach to treatment.
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- 2022
- Full Text
- View/download PDF
49. The COVID-19 vaccination campaign in Bhutan: strategy and enablers.
- Author
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Tsheten T, Tenzin P, Clements ACA, Gray DJ, Ugyel L, and Wangdi K
- Subjects
- Bhutan, Humans, Immunization Programs, SARS-CoV-2, Vaccination, COVID-19, COVID-19 Vaccines
- Abstract
Bhutan has reported a total of 2596 COVID-19 cases and three deaths as of September 15, 2021. With support from India, the United States, Denmark, the People's Republic of China, Croatia and other countries, Bhutan was able to conduct two rounds of nationwide vaccination campaign. While many countries struggle to overcome vaccine refusal or hesitancy due to complacency, a lack of trust, inconvenience and fear, escalated in some countries by anti-vaccine groups, Bhutan managed to inoculate more than 95% of its eligible populations in two rounds of vaccination campaign. Enabling factors of this successful vaccination campaign were strong national leadership, a well-coordinated national preparedness plan, and high acceptability of vaccine due to effective mass communication and social engagement led by religious figures, volunteers and local leaders. In this short report, we described the national strategic plan and enabling factors that led to the success of this historical vaccination campaign., (© 2022. The Author(s).)
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- 2022
- Full Text
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50. The Effects of Deworming and Multiple Micronutrients on Anaemia in Preschool Children in Bangladesh: Analysis of Five Cross-Sectional Surveys.
- Author
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Sarma H, Wangdi K, Tariqujjaman M, Das R, Rahman M, Kelly M, Ahmed T, and Gray DJ
- Subjects
- Anemia etiology, Bangladesh epidemiology, Child, Preschool, Female, Humans, Infant, Intestinal Diseases, Parasitic complications, Male, Prevalence, Recurrence, Anemia epidemiology, Anemia prevention & control, Antiparasitic Agents therapeutic use, Child Nutritional Physiological Phenomena physiology, Cross-Sectional Studies, Dietary Supplements, Eating physiology, Infant Nutritional Physiological Phenomena physiology, Intestinal Diseases, Parasitic drug therapy, Micronutrients administration & dosage
- Abstract
Anaemia is a major public health problem among children < 5 years of age in Bangladesh due to recurrent intestinal parasite infections. The aim of this study was to understand the association between combining deworming and MNP home fortification (MNP + Deworming) and the prevalence of anaemia among children < 5 years of age in Bangladesh. We used pooled data from five cross-sectional surveys and performed multivariable logistic regression and calculated crude and adjusted odds ratios (AORs) to quantify the association of anaemia with the exposure variables. A total of 9948 households were considered for this paper. In the unadjusted logistic regression, no significant association was detected between the effective MNP coverage and anaemia prevalence, but the associations were significant ( p < 0.001) between the deworming and anaemia prevalence and between the MNP + Deworming condition and anaemia prevalence. In the adjusted model, children who were exposed to both deworming and effective MNP coverage were 30% (AOR 0.70; 95% CI 0.52, 0.94; p = 0.018) less likely to be anaemic compared with children who were unexposed to combined MNP + Deworming. The combined effects of deworming and MNP supplementation on the reduction in anaemia prevalence highlighted the importance of using integrated and multidisciplinary intervention strategies.
- Published
- 2021
- Full Text
- View/download PDF
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