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1. Rare-Event Sampling of Epigenetic Landscapes and Phenotype Transitions

Author

Tse, Margaret J., Chu, Brian K., and Read, Elizabeth L.

Subjects
Quantitative Biology - Molecular Networks
Abstract

Stochastic simulation has been a powerful tool for studying the dynamics of gene regulatory networks, particularly in terms of understanding how cell-phenotype stability and fate-transitions are impacted by noisy gene expression. However, gene networks often have dynamics characterized by multiple attractors. Stochastic simulation is often inefficient for such systems, because most of the simulation time is spent waiting for rare, barrier-crossing events to occur. We present a rare-event simulation-based method for computing epigenetic landscapes and phenotype-transitions in metastable gene networks. Our computational pipeline was inspired by studies of metastability and barrier-crossing in protein folding, and provides an automated means of computing and visualizing essential stationary and dynamic information that is generally inaccessible to conventional simulation. Applied to a network model of pluripotency in Embryonic Stem Cells, our simulations revealed rare phenotypes and approximately Markovian transitions among phenotype-states, occurring with a broad range of timescales. The relative probabilities of phenotypes and the transition paths linking pluripotency and differentiation are sensitive to global kinetic parameters governing transcription factor-DNA binding kinetics. Our approach significantly expands the capability of stochastic simulation to investigate gene regulatory network dynamics, which may help guide rational cell reprogramming strategies. Our approach is also generalizable to other types of molecular networks and stochastic dynamics frameworks.

Published
2017
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2. Prevalence of trachoma in the area councils of the Federal Capital Territory, Nigeria: results of six population-based surveys

Author

Muhammad, Nasiru, Mpyet, Caleb, Adamu, Mohammed Dantani, William, Adamani, Umar, Murtala Muhammad, Muazu, Habila, Onyebuchi, Uwazoeke, Isiyaku, Sunday, Flueckiger, Rebecca M, Chu, Brian K, Willis, Rebecca, Pavluck, Alex, Dalhatu, Abbas, Ogoshi, Chris, Olobio, Nicholas, Gordon, Bruce A, Solomon, Anthony W, and Project, for the Global Trachoma Mapping

Subjects
Biomedical and Clinical Sciences, Public Health, Health Sciences, Infectious Diseases, Good Health and Well Being, Adolescent, Adult, Aged, Child, Child, Preschool, Cluster Analysis, Cross-Sectional Studies, Female, Humans, Hygiene, Infant, Male, Middle Aged, Nigeria, Prevalence, Sanitation, Trachoma, Water Supply, Young Adult, trichiasis, water and sanitation, GET2020, SDGs, Global Trachoma Mapping Project, Clinical Sciences, Opthalmology and Optometry, Public Health and Health Services, Epidemiology, Ophthalmology and optometry, Public health
Abstract

PurposeThe World Health Organization's (WHO's) global trachoma elimination programme recommends mapping of trachoma at district level for planning of elimination activities in affected populations. This study aimed to provide data on trachoma prevalence for the Area Councils of Nigeria's Federal Capital Territory (FCT).MethodsUsing the Global Trachoma Mapping Project (GTMP) protocols, in March and April 2014, we conducted a population-based cross-sectional survey in each of the six Area Councils of FCT. Signs were defined based on the WHO simplified grading scheme.Results98% to 100% of the targeted households were enrolled in each Area Council. The number of children aged 1-9 years examined per Area Council ranged from 867 to 1248. The number of persons aged ≥15 years examined ranged from 1302 to 1836. The age-adjusted prevalence of trachomatous inflammation-follicular in 1-9-year-olds was

Published
2018

3. Prevalence of trachoma in 13 Local Government Areas of Taraba State, Nigeria

Author

Umar, Murtala M, Mpyet, Caleb, Muhammad, Nasiru, Adamu, Mohammed D, Muazu, Habila, Onyebuchi, Uwazoeke, William, Adamani, Isiyaku, Sunday, Flueckiger, Rebecca M, Chu, Brian K, Willis, Rebecca, Pavluck, Alexandre L, Olobio, Nicholas, Apake, Ebenezer, Olamiju, Francisca, Solomon, Anthony W, and Project, for the Global Trachoma Mapping

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Good Health and Well Being, Adolescent, Adult, Aged, Child, Child, Preschool, Cluster Analysis, Cross-Sectional Studies, Female, Humans, Infant, Male, Middle Aged, Nigeria, Prevalence, Sanitation, Trachoma, Water Supply, Young Adult, trichiasis, SAFE strategy, Global Trachoma Mapping Project, Opthalmology and Optometry, Public Health and Health Services, Epidemiology, Ophthalmology and optometry, Public health
Abstract

PurposeThe purpose of these surveys was to determine the prevalence of trachomatous inflammation-follicular (TF) in children aged 1-9 years and trichiasis prevalence in persons aged ≥15 years, in 13 Local Government Areas (LGAs) of Taraba State, Nigeria.MethodsThe surveys followed Global Trachoma Mapping Project (GTMP) protocols. Twenty-five households were selected from each of 25 clusters in each LGA, using two-stage cluster sampling providing probability of selection proportional to cluster size. Survey teams examined all the residents of selected households aged ≥1 year for the clinical signs TF, trachomatous inflammation-intense (TI) and trichiasis.ResultsThe prevalence of TF in children aged 1-9 years in the 13 LGAs ranged from 0.0-5.0%; Ussa LGA had the highest prevalence of 5% (95%CI: 3.4-7.2). Trichiasis prevalence ranged from 0.0-0.8%; seven LGAs had trichiasis prevalences above the threshold for elimination. The backlog of trichiasis in the 13 LGAs (estimated combined population 1,959,375) was 3,185 people. There is need to perform surgery for at least 1,835 people to attain a trichiasis prevalence in each LGA of 80% of households with access to improved latrines.ConclusionOne of 13 LGAs requires antibiotic mass drug administration for active trachoma. Community-based trichiasis surgery needs to be provided in seven LGAs. There is a need to increase household-level access to improved washing water and latrines across the State.

Published
2018

4. Prevalence of trachoma in the Afar Region of Ethiopia: results of seven population-based surveys from the Global Trachoma Mapping Project

Author

Negash, Kassahun, Macleod, Colin, Adamu, Yilikal, Ahmed, Mohammed, Ibrahim, Mohamed, Ali, Mussa, Haileselassie, Tesfaye, Willis, Rebecca, Chu, Brian K, Dejene, Michael, Asrat, Atsbeha, Flueckiger, Rebecca M, Pavluck, Alexandre L, Solomon, Anthony W, and Project, for the Global Trachoma Mapping

Subjects
Biomedical and Clinical Sciences, Public Health, Health Sciences, Good Health and Well Being, Adolescent, Adult, Age Distribution, Aged, Child, Child, Preschool, Cross-Sectional Studies, Ethiopia, Female, Humans, Infant, Male, Middle Aged, Prevalence, Trachoma, Young Adult, trichiasis, trachomatous inflammation-follicular, prevalence, Afar, Global Trachoma Mapping, Global Trachoma Mapping Project, Clinical Sciences, Opthalmology and Optometry, Public Health and Health Services, Epidemiology, Ophthalmology and optometry, Public health
Abstract

PurposeTrachoma is to be eliminated as a public health problem by 2020. To help the process of planning interventions where needed, and to provide a baseline for later comparison, we set out to complete the map of trachoma in Afar, Ethiopia, by estimating trachoma prevalence in evaluation units (EUs) of grouped districts ("woredas").MethodsWe conducted seven community-based surveys from August to October 2013, using standardised Global Trachoma Mapping Project (GTMP) survey methodologies.ResultsWe enumerated 5065 households and 18,177 individuals in seven EUs covering 19 of Afar's 29 woredas; the other ten were not accessible. 16,905 individuals (93.0%) were examined, of whom 9410 (55.7%) were female. One EU incorporating four woredas (Telalak, Dalefage, Dewe, Hadele Ele) was shown to require full implementation of the SAFE strategy for three years before impact survey, with a trachomatous inflammation-follicular (TF) prevalence in 1-9-year-olds of 17.1% (95%CI 9.4-25.5), and a trichiasis prevalence in adults aged ≥15 years of 1.2% (95%CI 0.6-2.0). Five EUs, covering 13 woredas (Berahle, Aba'ala, Dupti, Kurri, Elidihare, Ayesayeta, Afamboo, Bure Mudaitu, Gewane, Amibara, Dulecho, Dalolo, and Konebo), had TF prevalences in children of 5-9.9% and need one round of azithromycin mass treatment and implementation of the F and E components of SAFE before re-survey; three of these EUs had trichiasis prevalences in adults ≥0.2%. The final EU (Mile, Ada'ar) had a sub-threshold TF prevalence and a trichiasis prevalence in adults just >0.2%.ConclusionTrachoma is a public health problem in Afar, and implementation of the SAFE strategy is required.

Published
2018

5. Trachoma in Viet Nam: results of 11 surveillance surveys conducted with the Global Trachoma Mapping Project

Author

Hiep, Nguyen Xuan, Ngondi, Jeremiah M, Anh, Vu Tuan, Dat, Tran Minh, Van An, Tran, Dung, Nguyen Chi, Thang, Nguyen Duy, Chu, Brian K, Willis, Rebecca, Bakhtiari, Ana, Pavluck, Alexandre L, Johnson, James, Sidwell, Joshua, Brady, Molly, Henry, Rob, Mosher, Aryc, Porco, Travis C, Lietman, Thomas M, Rotondo, Lisa A, Lewallen, Susan, Courtright, Paul, Solomon, Anthony W, and Project, for the Global Trachoma Mapping

Subjects
Biomedical and Clinical Sciences, Public Health, Health Sciences, Pediatric Research Initiative, Pediatric, Good Health and Well Being, Aged, Child, Child, Preschool, Cluster Analysis, Cross-Sectional Studies, Female, Humans, Infant, Male, Middle Aged, Prevalence, Trachoma, Trichiasis, Vietnam, Global Trachoma Mapping Project, SAFE strategy, surveillance survey, trichiasis, Viet Nam, Clinical Sciences, Opthalmology and Optometry, Public Health and Health Services, Epidemiology, Ophthalmology and optometry, Public health
Abstract

PurposeFollowing interventions against trachoma in Viet Nam, impact surveys conducted in 2003-2011 suggested that trachoma was no longer a public health problem. In 2014, we undertook surveillance surveys to estimate prevalence of trachomatous inflammation-follicular (TF) and trichiasis.MethodsA population-based prevalence survey was undertaken in 11 evaluation units (EUs) encompassing 24 districts, using Global Trachoma Mapping Project methods. A two-stage cluster sampling design was used in each EU, whereby 20 clusters and 60 children per cluster were sampled. Consenting eligible participants (children aged 1-9 years and adults aged ≥50 years) were examined for trachoma.ResultsA total of 9391 households were surveyed, and 20,185 participants (98.8% of those enumerated) were examined for trachoma. EU-level TF prevalence in 1-9-year-olds ranged from 0% to 1.6%. In one cluster (in Hà Giang Province), the percentage of children with TF was 10.3%. The overall pattern of cluster-level percentages of children with TF, however, was consistent with an exponential distribution, which would be consistent with trachoma disappearing. Among people aged ≥50 years, prevalence of trichiasis by EU ranged from 0% to 0.75%; these estimates are equivalent to 0-0.13% in all ages. The prevalence of trichiasis unknown to the health system among people aged ≥50 years, by EU, ranged from 0% to 0.17%, which is equivalent to 0-0.03% in all ages.ConclusionFindings suggest that trachoma is no longer a public health problem in any of the 11 EUs surveyed. However, given the high proportion of children with TF in one cluster in Hà Giang Province, further investigations will be undertaken.

Published
2018

6. Markov State Models of gene regulatory networks

Author

Chu, Brian K, Tse, Margaret J, Sato, Royce R, and Read, Elizabeth L

Subjects
Biochemistry and Cell Biology, Biological Sciences, Genetics, Bioengineering, Gene Regulatory Networks, Kinetics, Markov Chains, Models, Genetic, Multistable systems, Stochastic processes, Gene regulatory networks, Markov State Models, Cluster analysis, Computer Software, Other Medical and Health Sciences, Bioinformatics, Bioinformatics and computational biology, Medical biochemistry and metabolomics
Abstract

BackgroundGene regulatory networks with dynamics characterized by multiple stable states underlie cell fate-decisions. Quantitative models that can link molecular-level knowledge of gene regulation to a global understanding of network dynamics have the potential to guide cell-reprogramming strategies. Networks are often modeled by the stochastic Chemical Master Equation, but methods for systematic identification of key properties of the global dynamics are currently lacking.ResultsThe method identifies the number, phenotypes, and lifetimes of long-lived states for a set of common gene regulatory network models. Application of transition path theory to the constructed Markov State Model decomposes global dynamics into a set of dominant transition paths and associated relative probabilities for stochastic state-switching.ConclusionsIn this proof-of-concept study, we found that the Markov State Model provides a general framework for analyzing and visualizing stochastic multistability and state-transitions in gene networks. Our results suggest that this framework-adopted from the field of atomistic Molecular Dynamics-can be a useful tool for quantitative Systems Biology at the network scale.

Published
2017

7. Markov State Models of Gene Regulatory Networks

Author

Chu, Brian K., Tse, Margaret J., Sato, Royce R., and Read, Elizabeth L.

Subjects
Quantitative Biology - Molecular Networks
Abstract

Gene regulatory networks with dynamics characterized by multiple stable states underlie cell fate-decisions. Quantitative models that can link molecular-level knowledge of gene regulation to a global understanding of network dynamics have the potential to guide cell-reprogramming strategies. Networks are often modeled by the stochastic Chemical Master Equation, but methods for systematic identification of key properties of the global dynamics are currently lacking. We present a method for analyzing global dynamics of gene networks using the Markov State Model (MSM) framework, which utilizes a separation-of-timescales based clustering method to obtain a coarse-grained state transition graph that approximates global gene network dynamics. The method identifies the number, phenotypes, and lifetimes of long-lived network states. Application of transition path theory to the constructed MSM decomposes global dynamics into a set of dominant transition paths and associated relative probabilities for stochastic state-switching. In this proof-of-concept study, we found that the MSM provides a general framework for analyzing and visualizing stochastic multistability and state-transitions in gene networks. Our results suggest that the MSM framework, adopted from the field of atomistic Molecular Dynamics, can be a useful tool for quantitative Systems Biology at the network scale.

Published
2016

8. DNA-Binding Kinetics Determines the Mechanism of Noise-Induced Switching in Gene Networks

Author

Tse, Margaret J, Chu, Brian K, Roy, Mahua, and Read, Elizabeth L

Subjects
Genetics, Biotechnology, Underpinning research, 1.1 Normal biological development and functioning, Algorithms, Computer Simulation, DNA, Gene Expression Regulation, Kinetics, Models, Biological, Physical Sciences, Chemical Sciences, Biological Sciences, Biophysics
Abstract

Gene regulatory networks are multistable dynamical systems in which attractor states represent cell phenotypes. Spontaneous, noise-induced transitions between these states are thought to underlie critical cellular processes, including cell developmental fate decisions, phenotypic plasticity in fluctuating environments, and carcinogenesis. As such, there is increasing interest in the development of theoretical and computational approaches that can shed light on the dynamics of these stochastic state transitions in multistable gene networks. We applied a numerical rare-event sampling algorithm to study transition paths of spontaneous noise-induced switching for a ubiquitous gene regulatory network motif, the bistable toggle switch, in which two mutually repressive genes compete for dominant expression. We find that the method can efficiently uncover detailed switching mechanisms that involve fluctuations both in occupancies of DNA regulatory sites and copy numbers of protein products. In addition, we show that the rate parameters governing binding and unbinding of regulatory proteins to DNA strongly influence the switching mechanism. In a regime of slow DNA-binding/unbinding kinetics, spontaneous switching occurs relatively frequently and is driven primarily by fluctuations in DNA-site occupancies. In contrast, in a regime of fast DNA-binding/unbinding kinetics, switching occurs rarely and is driven by fluctuations in levels of expressed protein. Our results demonstrate how spontaneous cell phenotype transitions involve collective behavior of both regulatory proteins and DNA. Computational approaches capable of simulating dynamics over many system variables are thus well suited to exploring dynamic mechanisms in gene networks.

Published
2015

11. Prevalence of Trachoma in Kano State, Nigeria: Results of 44 Local Government Area-Level Surveys

Author

Mpyeta, Caleb, Muhammad, Nasiru, Adamu, Mohammed Dantani, Muazu, Habila, Umar, Murtala Muhammad, Goyol, Musa, Yahaya, Hadi Bala, Onyebuchi, Uwazoeke, Ogoshi, Chris, Hussaini, Tijjani, Isiyaku, Sunday, William, Adamani, Flueckiger, Rebecca M., Chu, Brian K., Willis, Rebecca, Pavluck, Alexandre L., Olobio, Nicholas, Phelan, Sophie, Macleod, Colin, and Solomon, Anthony W.

Subjects
Male, Veterinary medicine, Epidemiology, Cross-sectional study, Global Trachoma Mapping Project, Blindness, Adult women, 0302 clinical medicine, Hygiene, Risk Factors, Medicine, Cluster Analysis, Young adult, Child, media_common, Aged, 80 and over, education.field_of_study, Middle Aged, 3. Good health, Trachoma, Child, Preschool, Female, Adult, Trichiasis, Adolescent, media_common.quotation_subject, 030231 tropical medicine, Population, prevalence, Nigeria, Article, 03 medical and health sciences, Young Adult, Age Distribution, Humans, Sex Distribution, education, Local government area, Aged, Local Government, business.industry, Infant, medicine.disease, Ophthalmology, Cross-Sectional Studies, Kano State, 030221 ophthalmology & optometry, business, Demography
Abstract

Purpose We sought to determine the prevalence of trachoma in 44 Local Government Areas (LGAs) of Kano State, Nigeria. Methods A population-based prevalence survey was conducted in each Kano LGA. We used a two-stage systematic and quasi-random sampling strategy to select 25 households from each of 25 clusters in each LGA. All consenting household residents aged 1 year and above were examined for trachomatous inflammation–follicular (TF), trachomatous inflammation–intense (TI) and trichiasis. Results State-wide crude prevalence of TF in persons aged 1–9 years was 3.4% (95% CI 3.3–3.5%), and of trichiasis in those aged ≥15 years was 2.3% (95% CI 2.1–2.4%). LGA-level age- and sex-adjusted trichiasis prevalence in those aged ≥15 years ranged from 0.1% to 2.9%. All but 4 (9%) of 44 LGAs had trichiasis prevalences in adults above the elimination threshold of 0.2%. State-wide prevalence of trichiasis in adult women was significantly higher than in adult men (2.6% vs 1.8%; OR = 1.5, 95% CI 1.3–1.7; p = 0.001). Four of 44 LGAs had TF prevalences in 1–9 year-olds between 10 and 15%, while another six LGAs had TF prevalences between 5 and 9.9%. In 37 LGAs, >80% of households had access to water within 30 minutes round-trip, but household latrine access was >80% in only 19 LGAs. Conclusion Trichiasis is a public health problem in most LGAs in Kano. Surgeons need to be trained and deployed to provide community-based trichiasis surgery, with emphasis on delivery of such services to women. Antibiotics, facial cleanliness and environmental improvement are needed in 10 LGAs.

Published
2017

12. The global burden of trichiasis in 2016

Author

Flueckiger, Rebecca M., primary, Courtright, Paul, additional, Abdala, Mariamo, additional, Abdou, Amza, additional, Abdulnafea, Zaid, additional, Al-Khatib, Tawfik K., additional, Amer, Khaled, additional, Amiel, Olga Nelson, additional, Awoussi, Sossinou, additional, Bakhtiari, Ana, additional, Batcho, Wilfried, additional, Bella, Assumpta Lucienne, additional, Bennawi, Kamal Hashim, additional, Brooker, Simon J., additional, Chu, Brian K., additional, Dejene, Michael, additional, Dezoumbe, Djore, additional, Elshafie, Balgesa Elkheir, additional, Elvis, Aba Ange, additional, Fabrice, Djouma Nembot, additional, Omar, Fatma Juma, additional, François, Missamou, additional, François, Drabo, additional, Garap, Jambi, additional, Gichangi, Michael, additional, Goepogui, André, additional, Hammou, Jaouad, additional, Kadri, Boubacar, additional, Kabona, George, additional, Kabore, Martin, additional, Kalua, Khumbo, additional, Kamugisha, Mathias, additional, Kebede, Biruck, additional, Keita, Kaba, additional, Khan, Asad Aslam, additional, Kiflu, Genet, additional, Yibi, Makoy, additional, Mackline, Garae, additional, Macleod, Colin, additional, Manangazira, Portia, additional, Masika, Michael P., additional, Massangaie, Marilia, additional, Mduluza, Takafira, additional, Meno, Nabicassa, additional, Midzi, Nicholas, additional, Minnih, Abdallahi Ould, additional, Mishra, Sailesh, additional, Mpyet, Caleb, additional, Muraguri, Nicholas, additional, Mwingira, Upendo, additional, Nassirou, Beido, additional, Ndjemba, Jean, additional, Nieba, Cece, additional, Ngondi, Jeremiah, additional, Olobio, Nicholas, additional, Pavluck, Alex, additional, Phiri, Isaac, additional, Pullan, Rachel, additional, Qureshi, Babar, additional, Sarr, Boubacar, additional, Seiha, Do, additional, Chávez, Gloria Marina Serrano, additional, Sharma, Shekhar, additional, Sisaleumsak, Siphetthavong, additional, Southisombath, Khamphoua, additional, Stevens, Gretchen, additional, Woldendrias, Andeberhan Tesfazion, additional, Traoré, Lamine, additional, Turyaguma, Patrick, additional, Willis, Rebecca, additional, Yaya, Georges, additional, Yeo, Souleymane, additional, Zambroni, Francisco, additional, Zhao, Jialiang, additional, and Solomon, Anthony W., additional

Published
2019
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14. Prevalence of Trachoma in Kano State, Nigeria: Results of 44 Local Government Area-Level Surveys

Author

Mpyet, Caleb, Muhammad, Nasiru, Adamu, Mohammed Dantani, Muazu, Habila, Umar, Murtala Muhammad, Goyol, Musa, Yahaya, Hadi Bala, Onyebuchi, Uwazoeke, Ogoshi, Chris, Hussaini, Tijjani, Isiyaku, Sunday, William, Adamani, Flueckiger, Rebecca M, Chu, Brian K, Willis, Rebecca, Pavluck, Alexandre L, Olobio, Nicholas, Phelan, Sophie, Macleod, Colin, Solomon, Anthony W, and Global Trachoma Mapping Project

Abstract

PURPOSE: We sought to determine the prevalence of trachoma in 44 Local Government Areas (LGAs) of Kano State, Nigeria. METHODS: A population-based prevalence survey was conducted in each Kano LGA. We used a two-stage systematic and quasi-random sampling strategy to select 25 households from each of 25 clusters in each LGA. All consenting household residents aged 1 year and above were examined for trachomatous inflammation-follicular (TF), trachomatous inflammation-intense (TI) and trichiasis. RESULTS: State-wide crude prevalence of TF in persons aged 1-9 years was 3.4% (95% CI 3.3-3.5%), and of trichiasis in those aged ≥15 years was 2.3% (95% CI 2.1-2.4%). LGA-level age- and sex-adjusted trichiasis prevalence in those aged ≥15 years ranged from 0.1% to 2.9%. All but 4 (9%) of 44 LGAs had trichiasis prevalences in adults above the elimination threshold of 0.2%. State-wide prevalence of trichiasis in adult women was significantly higher than in adult men (2.6% vs 1.8%; OR = 1.5, 95% CI 1.3-1.7; p = 0.001). Four of 44 LGAs had TF prevalences in 1-9-year-olds between 10 and 15%, while another six LGAs had TF prevalences between 5 and 9.9%. In 37 LGAs, >80% of households had access to water within 30 minutes round-trip, but household latrine access was >80% in only 19 LGAs. CONCLUSION: Trichiasis is a public health problem in most LGAs in Kano. Surgeons need to be trained and deployed to provide community-based trichiasis surgery, with emphasis on delivery of such services to women. Antibiotics, facial cleanliness and environmental improvement are needed in 10 LGAs.

Published
2017

15. Integrated Mapping of Yaws and Trachoma in the Five Northern-Most Provinces of Vanuatu

Author

Taleo, Fasihah, Macleod, Colin K, Marks, Michael, Sokana, Oliver, Last, Anna, Willis, Rebecca, Garae, Mackline, Bong, Annie, Chu, Brian K, Courtright, Paul, Kool, Jacob, Taleo, George, Rory, Jean Jacque, and Solomon, Anthony W

Subjects
Bacterial Diseases, Male, Eye Diseases, Pathology and Laboratory Medicine, Treponematoses, Geographical Locations, Vanuatu, Risk Factors, Surveys and Questionnaires, Medicine and Health Sciences, Public and Occupational Health, Sanitation, Chlamydia, Child, Immune Response, Aged, 80 and over, Family Characteristics, Middle Aged, Bacterial Pathogens, Anti-Bacterial Agents, Infectious Diseases, Chlamydia Trachomatis, Medical Microbiology, Child, Preschool, Female, Pathogens, Environmental Health, Research Article, Neglected Tropical Diseases, Adult, Adolescent, Oceania, Immunology, Microbiology, Young Adult, Signs and Symptoms, Diagnostic Medicine, Humans, Microbial Pathogens, Aged, Trachoma, Inflammation, Bacteria, Organisms, Biology and Life Sciences, Infant, Tropical Diseases, Health Care, Ophthalmology, Cross-Sectional Studies, Logistic Models, Yaws, People and Places, Multivariate Analysis, Lesions
Abstract

Yaws and trachoma are targeted for eradication and elimination as public health problems. In trachoma-endemic populations mass administration of azithromycin can simultaneously treat yaws. We conducted a population-based prevalence survey in the five northernmost provinces of Vanuatu, where trachoma and yaws are suspected to be co-endemic. Clinical signs of trachoma were evaluated using the WHO simplified grading system, and skin examination with a serological rapid diagnostic test used to identify yaws. We enrolled 1004 households in 59 villages over 16 islands, and examined 3650 individuals of all ages for trachoma. The overall adjusted prevalence of trachomatous inflammation-follicular (TF) in 1–9 year-olds was 12.0% (95% Confidence Interval: 8.1–16.7%), and the overall adjusted prevalence of TT in those aged 15 years and greater was 0.04% (95% CI 0–0.14%). In multivariate analysis, the odds of children having TF was 2.6 (95% CI = 1.5–4.4) times higher in households with unimproved latrines, and independently associated with the number of children in the household (OR 1.3, 95% CI = 1.0–1.6 for each additional child). We examined the skin of 821 children aged 5–14 years. Two children had yaws, giving an estimated prevalence of active yaws in those aged 5–14 years of 0.2% (95% CI = 0.03–0.9%). Mass treatment with azithromycin is recommended in these provinces. Given the apparent low burden of yaws, integration of yaws and trachoma control programmes is likely to be useful and cost-effective to national programmes., Author Summary Yaws and trachoma are infectious diseases targeted by the World Health Organization (WHO) for eradication and elimination as a public health problem, respectively. Both diseases are found in the rural, isolated and underserved communities of the world’s poorest countries. The WHO strategy for trachoma elimination includes Mass Drug Administration (MDA) of the antibiotic azithromycin, with population-based prevalence surveys required to determine where interventions are needed. As yaws can also be treated with azithromycin, in co-endemic areas, azithromycin MDA will likely treat both infections. We conducted an integrated trachoma and yaws prevalence survey in establish the prevalence of both diseases in the 5 northern-most provinces of Vanuatu. The estimated prevalence of trachomatous inflammation—follicular (TF, a sign of C. trachomatis infection) in children aged 1–9 years was 12.0%, and the estimated prevalence of trachomatous trichiasis (TT, advanced, potentially blinding disease) in adults aged 15 years and above was 0.04%. Two children had yaws, giving an estimated prevalence of active yaws in those aged 5–14 years of 0.2%. Mass treatment with azithromycin is recommended in these provinces. Given the apparent low burden of yaws, integration of yaws and trachoma control programmes is likely to be useful and cost-effective to national programmes.

Published
2017

16. The Health and Economic Burdens of Lymphatic Filariasis Prior to Mass Drug Administration Programs.

Author

Mathew, Christopher G, Bettis, Alison A, Chu, Brian K, English, Mike, Ottesen, Eric A, Bradley, Mark H, and Turner, Hugo C

Subjects
PREVENTION of infectious disease transmission, DISEASES, ECONOMIC aspects of diseases, DRUG administration, ELEPHANTIASIS, LABOR productivity, LIFE expectancy, MEDICAL care costs, PEOPLE with disabilities, PUBLIC health
Abstract

Background The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000 with the goal of eliminating lymphatic filariasis (LF) as a public health problem by 2020. Despite considerable progress, the current prevalence is around 60% of the 2000 figure, with the deadline looming a year away. Consequently, there is a continued need for investment in both the mass drug administration (MDA) and morbidity management programs, and this paper aims to demonstrate that need by estimating the health and economic burdens of LF prior to MDA programs starting in GPELF areas. Methods A previously developed model was used to estimate the numbers of individuals infected and individuals with symptomatic disease, along with the attributable number of disability-adjusted life years (DALYs). The economic burden was calculated by quantifying the costs incurred by the health-care system in managing clinical cases, the patients' out-of-pocket costs, and their productivity costs. Results Prior to the MDA program, approximately 129 million people were infected with LF, of which 43 million had clinical disease, corresponding to a DALY burden of 5.25 million. The average annual economic burden per chronic case was US $115, the majority of which resulted from productivity costs. The total economic burden of LF was estimated at US $5.8 billion annually. Conclusions These results demonstrate the magnitude of the LF burden and highlight the continued need to support the GPELF. Patients with clinical disease bore the majority of the economic burden, but will not benefit much from the current MDA program, which is aimed at reducing transmission. This assessment further highlights the need to scale up morbidity management programs. [ABSTRACT FROM AUTHOR]

Published
2020
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18. The global burden of trichiasis in 2016

Author

Flueckiger, Rebecca M, primary, Courtright, Paul, additional, Abdala, Mariamo, additional, Abdou, Amza, additional, Abdulnafea, Zaid, additional, Al-Khatib, Tawfik K, additional, Amer, Khaled, additional, Amiel, Olga Nelson, additional, Awoussi, Sossinou, additional, Bakhtiari, Ana, additional, Batcho, Wilfried, additional, Bella, Assumpta Lucienne, additional, Bennawi, Kamal Hashim, additional, Brooker, Simon J, additional, Chu, Brian K, additional, Dejene, Michael, additional, Dezoumbe, Djore, additional, Elshafie, Balgesa Elkheir, additional, Elvis, Aba Ange, additional, Fabrice, Djouma Nembot, additional, Omar, Fatma Juma, additional, François, Missamou, additional, François, Drabo, additional, Garap, Jambi, additional, Gichangi, Michael, additional, Goepogui, André, additional, Hammou, Jaouad, additional, Kadri, Boubacar, additional, Kabona, George, additional, Kabore, Martin, additional, Kalua, Khumbo, additional, Kamugisha, Mathias, additional, Kebede, Biruck, additional, Keita, Kaba, additional, Khan, Asad Aslam, additional, Kiflu, Genet, additional, Mackline, Garae, additional, Macleod, Colin, additional, Manangazira, Portia, additional, Masika, Michael P, additional, Massangaie, Marilia, additional, Mduluza, Taka Fira, additional, Meno, Nabicassa, additional, Midzi, Nicholas, additional, Minnih, Abdallahi Ould, additional, Mishra, Sailesh, additional, Mpyet, Caleb, additional, Muraguri, Nicholas, additional, Mwingira, Upendo, additional, Nassirou, Beido, additional, Ndjemba, Jean, additional, Nieba, Cece, additional, Ngondi, Jeremiah, additional, Olobio, Nicholas, additional, Pavluck, Alex, additional, Phiri, Isaac, additional, Pullan, Rachel, additional, Qureshi, Babar, additional, Sarr, Boubacar, additional, Seiha, Do, additional, Serrano Chávez, Gloria Marina, additional, Sharma, Shekhar, additional, Sisaleumsak, Siphetthavong, additional, Southisombath, Khamphoua, additional, Stevens, Gretchen, additional, Woldendrias, Andeberhan Tesfazion, additional, Traoré, Lamine, additional, Turyaguma, Patrick, additional, Willis, Rebecca, additional, Yaya, Georges, additional, Yeo, Souleymane, additional, Zambroni, Francisco, additional, Zhao, Jialiang, additional, and Solomon, Anthony W, additional

Published
2018
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19. Application of a household-based molecular xenomonitoring strategy to evaluate the lymphatic filariasis elimination program in Tamil Nadu, India

Author

Subramanian, Swaminathan, primary, Jambulingam, Purushothaman, additional, Chu, Brian K., additional, Sadanandane, Candasamy, additional, Vasuki, Venkatesan, additional, Srividya, Adinarayanan, additional, Mohideen AbdulKader, Mohamed S., additional, Krishnamoorthy, Kaliannagounder, additional, Raju, Harikishan K., additional, Laney, Sandra J., additional, Williams, Steven A., additional, and Henderson, Ralph H., additional

Published
2017
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20. Partnering for impact: Integrated transmission assessment surveys for lymphatic filariasis, soil transmitted helminths and malaria in Haiti

Author

Knipes, Alaine Kathryn, primary, Lemoine, Jean Frantz, additional, Monestime, Franck, additional, Fayette, Carl R., additional, Direny, Abdel N., additional, Desir, Luccene, additional, Beau de Rochars, Valery E., additional, Streit, Thomas G., additional, Renneker, Kristen, additional, Chu, Brian K., additional, Chang, Michelle A., additional, Mace, Kimberly E., additional, Won, Kimberly Y., additional, and Lammie, Patrick J., additional

Published
2017
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23. Mapping Trachoma in Kaduna State, Nigeria: Results of 23 Local Government Area-Level, Population-Based Prevalence Surveys

Author

Muhammad, Nasiru, primary, Mpyet, Caleb, additional, Adamu, Mohammed Dantani, additional, William, Adamani, additional, Umar, Murtala Muhammad, additional, Goyol, Musa, additional, Muazu, Habila, additional, Onyebuchi, Uwaezuoke, additional, Isiyaku, Sunday, additional, Flueckiger, Rebecca M., additional, Chu, Brian K., additional, Willis, Rebecca, additional, Pavluck, Alexandre L., additional, Alhassan, Abdullahi, additional, Olobio, Nicholas, additional, Gordon, Bruce A., additional, and Solomon, Anthony W., additional

Published
2016
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24. Prevalence of Trachoma in Benishangul Gumuz Region, Ethiopia: Results of Seven Population-Based Surveys from the Global Trachoma Mapping Project

Author

Adamu, Yilikal, primary, Macleod, Colin, additional, Adamu, Liknaw, additional, Fikru, Wirtu, additional, Kidu, Beyene, additional, Abashawl, Aida, additional, Dejene, Michael, additional, Chu, Brian K., additional, Flueckiger, Rebecca M., additional, Willis, Rebecca, additional, Pavluck, Alexandre L., additional, and Solomon, Anthony W., additional

Published
2016
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25. The Prevalence of Trachoma in Tigray Region, Northern Ethiopia: Results of 11 Population-Based Prevalence Surveys Completed as Part of the Global Trachoma Mapping Project

Author

Sherief, Sadik Taju, primary, Macleod, Colin, additional, Gigar, Goitum, additional, Godefay, Hagos, additional, Abraha, Atakelit, additional, Dejene, Michael, additional, Kello, Amir B., additional, Belete, Aberash, additional, Assefa, Yitbarek, additional, Willis, Rebecca, additional, Chu, Brian K., additional, and Solomon, Anthony W., additional

Published
2016
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26. Prevalence of and Risk Factors for Trachoma in Southern Nations, Nationalities, and Peoples’ Region, Ethiopia: Results of 40 Population-Based Prevalence Surveys Carried Out with the Global Trachoma Mapping Project

Author

Adera, Tesfaye Haileselassie, primary, Macleod, Colin, additional, Endriyas, Misganu, additional, Dejene, Michael, additional, Willis, Rebecca, additional, Chu, Brian K., additional, Letamo, Yohannes, additional, Misganaw, Tebeje, additional, Mesele, Tamiru, additional, Mekonnen, Emebet, additional, Sisay, Alemayehu, additional, Mulugeta, Yeneneh, additional, Alemayehu, Wondu, additional, Kalua, Khumbo, additional, Destu, Tezera Kifle, additional, Adamu, Yilikal, additional, Smith, Jennifer L., additional, Beyene, Abu, additional, Tadesse, Addisu, additional, and Solomon, Anthony W., additional

Published
2016
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27. Prevalence of Trachoma in Bauchi State, Nigeria: Results of 20 Local Government Area-Level Surveys

Author

Mpyet, Caleb, primary, Muhammad, Nasiru, additional, Adamu, Mohammed Dantani, additional, Muazu, Habila, additional, Umar, Murtala Muhammad, additional, Abdull, Mohammed, additional, Alada, Joel, additional, Goyol, Musa, additional, Onyebuchi, Uwaezuoke, additional, Olamiju, Francisca, additional, Isiyaku, Sunday, additional, William, Adamani, additional, Nwobi, Benjamin C., additional, Willis, Rebecca, additional, Flueckiger, Rebecca Mann, additional, Pavluck, Alex, additional, Chu, Brian K., additional, Olobio, Nicholas, additional, and Solomon, Anthony W., additional

Published
2016
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28. Prevalence of Trachoma in Katsina State, Nigeria: Results of 34 District-Level Surveys

Author

Mpyet, Caleb, primary, Muhammad, Nasiru, additional, Adamu, Mohammed Dantani, additional, Muazu, Habila, additional, Umar, Murtala Mohammad, additional, Goyol, Musa, additional, Onyebuchi, Uwazoeke, additional, Chima, Ima, additional, Idris, Haliru, additional, William, Adamani, additional, Isiyaku, Sunday, additional, Nwobi, Benjamin, additional, Flueckiger, Rebecca Mann, additional, Willis, Rebecca, additional, Pavluck, Alexandre, additional, Chu, Brian K., additional, Olobio, Nicholas, additional, and Solomon, Anthony W., additional

Published
2016
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29. Trachoma Mapping in Gombe State, Nigeria: Results of 11 Local Government Area Surveys

Author

Mpyet, Caleb, primary, Muhammad, Nasiru, additional, Adamu, Mohammed Dantani, additional, Muazu, Habila, additional, Umar, Murtala Muhammad, additional, Alada, Joel, additional, Onyebuchi, Uwazoeke, additional, Olamiju, Fracisca, additional, Isiyaku, Sunday, additional, William, Adamani, additional, Willis, Rebecca, additional, Flueckiger, Rebecca Mann, additional, Pavluck, Alexandre, additional, Chu, Brian K., additional, Mohammed, Danjuma, additional, Olobio, Nicholas, additional, and Solomon, Anthony W., additional

Published
2016
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32. Quality Assurance and Quality Control in the Global Trachoma Mapping Project.

Author

Solomon, Anthony W., Willis, Rebecca, Pavluck, Alexandre L., Alemayehu, Wondu, Bakhtiari, Ana, Bovill, Sarah, Chu, Brian K., Courtright, Paul, Dejene, Michael, Downs, Philip, Flueckiger, Rebecca M., Haddad, Danny, Hooper, P. J., Kalua, Khumbo, Kebede, Biruck, Kello, Amir Bedri, Macleod, Colin K., McCullagh, Siobhain, Millar, Tom, and Mpyet, Caleb

Published
2018
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33. Trachoma in Viet Nam: results of 11 surveillance surveys conducted with the Global Trachoma Mapping Project.

Author

for the Global Trachoma Mapping Project, Hiep, Nguyen Xuan, Anh, Vu Tuan, Dat, Tran Minh, An, Tran Van, Dung, Nguyen Chi, Thang, Nguyen Duy, Lewallen, Susan, Courtright, Paul, Solomon, Anthony W., Ngondi, Jeremiah M., Chu, Brian K., Willis, Rebecca, Bakhtiari, Ana, Pavluck, Alexandre L., Johnson, James, Sidwell, Joshua, Brady, Molly, Rotondo, Lisa A., and Henry, Rob

Subjects
TRACHOMA, HEALTH surveys, INFLAMMATION, SAMPLING methods
Abstract

Purpose: Following interventions against trachoma in Viet Nam, impact surveys conducted in 2003-2011 suggested that trachoma was no longer a public health problem. In 2014, we undertook surveillance surveys to estimate prevalence of trachomatous inflammation—follicular (TF) and trichiasis. Methods: A population-based prevalence survey was undertaken in 11 evaluation units (EUs) encompassing 24 districts, using Global Trachoma Mapping Project methods. A two-stage cluster sampling design was used in each EU, whereby 20 clusters and 60 children per cluster were sampled. Consenting eligible participants (children aged 1-9 years and adults aged ≥50 years) were examined for trachoma. Results: A total of 9391 households were surveyed, and 20,185 participants (98.8% of those enumerated) were examined for trachoma. EU-level TF prevalence in 1-9-year-olds ranged from 0% to 1.6%. In one cluster (in Hà Giang Province), the percentage of children with TF was 10.3%. The overall pattern of cluster-level percentages of children with TF, however, was consistent with an exponential distribution, which would be consistent with trachoma disappearing. Among people aged ≥50 years, prevalence of trichiasis by EU ranged from 0% to 0.75%; these estimates are equivalent to 0-0.13% in all ages. The prevalence of trichiasis unknown to the health system among people aged ≥50 years, by EU, ranged from 0% to 0.17%, which is equivalent to 0-0.03% in all ages. Conclusion: Findings suggest that trachoma is no longer a public health problem in any of the 11 EUs surveyed. However, given the high proportion of children with TF in one cluster in Hà Giang Province, further investigations will be undertaken. [ABSTRACT FROM AUTHOR]

Published
2018
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34. Prevalance of trachoma in 13 Local Government Areas of Taraba State, Nigeria.

Author

for the Global Trachoma Mapping Project, Umar, Murtala M., Olamiju, Francisca, Solomon, Anthony W., Mpyet, Caleb, William, Adamani, Isiyaku, Sunday, Muhammad, Nasiru, Adamu, Mohammed D., Muazu, Habila, Onyebuchi, Uwazoeke, Olobio, Nicholas, Flueckiger, Rebecca M., Chu, Brian K., Willis, Rebecca, Pavluck, Alexandre L., and Apake, Ebenezer

Subjects
TRACHOMA, LOCAL government, PUBLIC health, INFLAMMATION
Abstract

Background: The purpose of these surveys was to determine the prevalence of trachomatous inflammation—follicular (TF) in children aged 1-9 years and trichiasis prevalence in persons aged ≥15 years, in 13 Local Government Areas (LGAs) of Taraba State, Nigeria. Method: The surveys followed Global Trachoma Mapping Project (GTMP) protocols. Twenty-five households were selected from each of 25 clusters in each LGA, using two-stage cluster sampling providing probability of selection proportional to cluster size. Survey teams examined all the residents of selected households aged ≥1 year for the clinical signs TF, trachomatous inflammation—intense (TI) and trichiasis. Results: The prevalence of TF in children aged 1-9 years in the 13 LGAs ranged from 0.0-5.0%; Ussa LGA had the highest prevalence of 5% (95%CI: 3.4-7.2). Trichiasis prevalence ranged from 0.0-0.8%; seven LGAs had trichiasis prevalences above the threshold for elimination. The backlog of trichiasis in the 13 LGAs (estimated combined population 1,959,375) was 3,185 people. There is need to perform surgery for at least 1,835 people to attain a trichiasis prevalence in each LGA of <0.2% in persons aged ≥15 years. In six of the 13 LGAs, 80% of households could access washing water within 1 km of the household, but only one LGA had >80% of households with access to improved latrines. Conclusion: One of 13 LGAs requires antibiotic mass drug administration for active trachoma. Community-based trichiasis surgery needs to be provided in seven LGAs. There is a need to increase household-level access to improved washing water and latrines across the State. [ABSTRACT FROM AUTHOR]

Published
2018
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35. Prevalence of trachoma in the Afar Region of Ethiopia: results of seven population-based surveys from the Global Trachoma Mapping Project.

Author

for the Global Trachoma Mapping Project, Negash, Kassahun, Asrat, Atsbeha, Solomon, Anthony W., Macleod, Colin, Adamu, Yilikal, Ali, Mussa, Ahmed, Mohammed, Ibrahim, Mohamed, Haileselassie, Tesfaye, Willis, Rebecca, Chu, Brian K., Flueckiger, Rebecca M., Pavluck, Alexandre L., and Dejene, Michael

Subjects
TRACHOMA, INFLAMMATION, DEMOGRAPHIC surveys, BLINDNESS
Abstract

Purpose: Trachoma is to be eliminated as a public health problem by 2020. To help the process of planning interventions where needed, and to provide a baseline for later comparison, we set out to complete the map of trachoma in Afar, Ethiopia, by estimating trachoma prevalence in evaluation units (EUs) of grouped districts ("woredas"). Methods: We conducted seven community-based surveys from August to October 2013, using standardised Global Trachoma Mapping Project (GTMP) survey methodologies. Results: We enumerated 5065 households and 18,177 individuals in seven EUs covering 19 of Afar's 29 woredas; the other ten were not accessible. 16,905 individuals (93.0%) were examined, of whom 9410 (55.7%) were female. One EU incorporating four woredas (Telalak, Dalefage, Dewe, Hadele Ele) was shown to require full implementation of the SAFE strategy for three years before impact survey, with a trachomatous inflammation-follicular (TF) prevalence in 1-9-year-olds of 17.1% (95%CI 9.4-25.5), and a trichiasis prevalence in adults aged ≥15 years of 1.2% (95%CI 0.6-2.0). Five EUs, covering 13 woredas (Berahle, Aba'ala, Dupti, Kurri, Elidihare, Ayesayeta, Afamboo, Bure Mudaitu, Gewane, Amibara, Dulecho, Dalolo, and Konebo), had TF prevalences in children of 5-9.9% and need one round of azithromycin mass treatment and implementation of the F and E components of SAFE before re-survey; three of these EUs had trichiasis prevalences in adults ≥0.2%. The final EU (Mile, Ada'ar) had a sub-threshold TF prevalence and a trichiasis prevalence in adults just >0.2%. Conclusion: Trachoma is a public health problem in Afar, and implementation of the SAFE strategy is required. [ABSTRACT FROM AUTHOR]

Published
2018
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36. Prevalence of trachoma in the area councils of the Federal Capital Territory, Nigeria: results of six population-based surveys.

Author

for the Global Trachoma Mapping Project, Muhammad, Nasiru, Adamu, Mohammed Dantani, Ogoshi, Chris, Gordon, Bruce A., Solomon, Anthony W., William, Adamani, Isiyaku, Sunday, Mpyet, Caleb, Umar, Murtala Muhammad, Muazu, Habila, Onyebuchi, Uwazoeke, Olobio, Nicholas, Flueckiger, Rebecca M., Chu, Brian K., Willis, Rebecca, Pavluck, Alex, and Dalhatu, Abbas

Subjects
TRACHOMA, WATER quality, SANITATION, DEMOGRAPHIC surveys
Abstract

Background: The World Health Organization's (WHO's) global trachoma elimination programme recommends mapping of trachoma at district level for planning of elimination activities in affected populations. This study aimed to provide data on trachoma prevalence for the Area Councils of Nigeria's Federal Capital Territory (FCT). Methodology: Using the Global Trachoma Mapping Project (GTMP) protocols, in March and April 2014, we conducted a population-based cross-sectional survey in each of the six Area Councils of FCT. Signs were defined based on the WHO simplified grading scheme. Results: 98% to 100% of the targeted households were enrolled in each Area Council. The number of children aged 1-9 years examined per Area Council ranged from 867 to 1248. The number of persons aged ≥15 years examined ranged from 1302 to 1836. The age-adjusted prevalence of trachomatous inflammation—follicular in 1-9-year-olds was <5% in each Area Council. The age- and gender-adjusted prevalence of trichiasis in those aged ≥15 years ranged from 0.0% to 0.3%; two Area Councils (Gwagwalada and Kwali) had prevalences above the 0.2% elimination threshold. The proportion of households with access to improved latrines and water sources ranged from 17 to 90% and 39 to 85% respectively. Conclusions: Gwagwalada and Kwali Area Councils need to perform more trichiasis surgeries to attain the trichiasis elimination prevalence target of 0.2% in persons aged ≥15 years. No Area Council requires mass antibiotic administration for the purposes of trachoma's elimination as a public health problem. All Area Councils need to accelerate provision of access to improved water sources and latrine facilities, to achieve universal coverage. [ABSTRACT FROM AUTHOR]

Published
2018
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37. The Global Trachoma Mapping Project: Methodology of a 34-Country Population-Based Study

Author

Solomon, Anthony W., primary, Pavluck, Alexandre L., additional, Courtright, Paul, additional, Aboe, Agatha, additional, Adamu, Liknaw, additional, Alemayehu, Wondu, additional, Alemu, Menbere, additional, Alexander, Neal D. E., additional, Kello, Amir Bedri, additional, Bero, Berhanu, additional, Brooker, Simon J., additional, Chu, Brian K., additional, Dejene, Michael, additional, Emerson, Paul M., additional, Flueckiger, Rebecca M., additional, Gadisa, Solomon, additional, Gass, Katherine, additional, Gebre, Teshome, additional, Habtamu, Zelalem, additional, Harvey, Erik, additional, Haslam, Dominic, additional, King, Jonathan D., additional, Mesurier, Richard Le, additional, Lewallen, Susan, additional, Lietman, Thomas M., additional, MacArthur, Chad, additional, Mariotti, Silvio P., additional, Massey, Anna, additional, Mathieu, Els, additional, Mekasha, Addis, additional, Millar, Tom, additional, Mpyet, Caleb, additional, Muñoz, Beatriz E., additional, Ngondi, Jeremiah, additional, Ogden, Stephanie, additional, Pearce, Joseph, additional, Sarah, Virginia, additional, Sisay, Alemayehu, additional, Smith, Jennifer L., additional, Taylor, Hugh R., additional, Thomson, Jo, additional, West, Sheila K., additional, Willis, Rebecca, additional, Bush, Simon, additional, Haddad, Danny, additional, and Foster, Allen, additional

Published
2015
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38. Application of a household-based molecular xenomonitoring strategy to evaluate the lymphatic filariasis elimination program in Tamil Nadu, India.

Author

Swaminathan, Subramanian, Purushothaman, Jambulingam, Chu, Brian K., Candasamy, Sadanandane, Venkatesan, Vasuki, Adinarayanan, Srividya, Mohamed Sathak M., AbdulKhader, Kaliannagounder, Krishnamoorthy, Raju, Harikishan K., Laney, Sandra J., Williams, Steven A., and Henderson, Ralph H.

Subjects
FILARIASIS, CULEX, COMMUNICABLE diseases, SURVEILLANCE detection, MOSQUITOES
Abstract

Background: The monitoring and evaluation of lymphatic filariasis (LF) has largely relied on the detection of antigenemia and antibodies in human populations. Molecular xenomonitoring (MX), the detection of parasite DNA/RNA in mosquitoes, may be an effective complementary method, particularly for detecting signals in low-level prevalence areas where Culex is the primary mosquito vector. This paper investigated the application of a household-based sampling method for MX in Tamil Nadu, India. Methods: MX surveys were conducted in 2010 in two evaluation units (EUs): 1) a hotspot area, defined as sites with community microfilaria prevalence ≥1%, and 2) a larger area that also encompassed the hotspots. Households were systematically selected using a sampling interval proportional to the number of households in the EU. Mosquito pools were collected and analyzed by real-time polymerase chain reaction (qPCR). Two independent samples were taken in each EU to assess reproducibility of results. Follow-up surveys were conducted in 2012. Results: In 2010, the proportion of positive pools in the hotspot EU was 49.3% compared to 23.4% in the overall EU. In 2012, pool positivity was significantly reduced to 24.3% and 6.5%, respectively (p<0.0001). Pool positivity based on independent samples taken from each EU in 2010 and 2012 were not significantly different except for the hotspot EU in 2012 (p = 0.009). The estimated prevalence of infection in mosquitoes, measured by PoolScreen, declined from 2.2–2.7% in 2010 to 0.6–1.2% in 2012 in the hotspot area and from 0.9–1.1% to 0.2–0.3% in the larger area. Conclusions: The household-based sampling strategy for MX led to mostly reproducible results and supported the observed LF infection trends found in humans. MX has the potential to be a cost-effective, non-invasive monitoring and evaluation tool with sensitive detection of infection signals in low prevalence settings. Further investigation and application of this sampling strategy for MX are recommended to support its adoption as a standardized method for global LF elimination programs. [ABSTRACT FROM AUTHOR]

Published
2017
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39. Prevalence of Trachoma in Niger State, North Central Nigeria: Results of 25 Population-Based Prevalence Surveys Carried Out with the Global Trachoma Mapping Project.

Author

Adamu, Mohammed Dantani, Mpyet, Caleb, Muhammad, Nasiru, Umar, Murtala Muhammad, Muazu, Habila, Olamiju, Francisca, Isiyaku, Sunday, Onyebuchi, Uwazoeke, Bosso, Usman Abubakar, William, Adamani, Nwobi, Benjamin C., Willis, Rebecca, Flueckiger, Rebecca Mann, Pavluck, Alexandre, Chu, Brian K., Olobio, Nicholas, and Solomon, Anthony W.

Subjects
TRACHOMA, EPIDEMIOLOGY, DISEASE prevalence, IMMUNOLOGY of inflammation
Abstract

Purpose: To determine the prevalence of trachoma in each of the 25 local government areas (LGAs) of Niger State, Nigeria. Methods: A population-based cross-sectional survey was conducted in each Niger State LGA between March and April 2014, as part of the Global Trachoma Mapping Project (GTMP). GTMP protocols were used in planning and conduct of the surveys. Using probability proportional to size, 25 clusters were selected; in each of these clusters, 25 households were enrolled for the survey. All residents aged 1 year and older were examined by GTMP-certified graders for trachomatous inflammation – follicular (TF) and trichiasis using the World Health Organization simplified grading scheme. Additionally, we collected data on household water and sanitation facilities. Results: Only one LGA (Kontagora) had TF prevalence in 1–9-year-olds above 10%; one other LGA (Rafi) had TF prevalence between 5.0 and 9.9%. Six LGAs need trichiasis surgical services provided to achieve a prevalence of <1 case of trichiasis per 1000 total population. The proportion of households with access to improved water sources ranged from 23 to 100%, while household-level access to improved latrines ranged from 8 to 100% across the LGAs. Conclusion: The prevalence of trachoma is relatively low in most of Niger State. There is a need for community-based trichiasis surgical services in a small number of LGAs. The trachoma elimination program could engage water and sanitation agencies to augment access to improved water and sanitation facilities, for human rights reasons. Kontagora and Rafi need community-based interventions to reduce the prevalence of active trachoma. [ABSTRACT FROM PUBLISHER]

Published
2016
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40. Prevalence of and Risk Factors for Trachoma in Oromia Regional State of Ethiopia: Results of 79 Population-Based Prevalence Surveys Conducted with the Global Trachoma Mapping Project.

Author

Bero, Berhanu, Macleod, Colin, Alemayehu, Wondu, Gadisa, Solomon, Abajobir, Ahmed, Adamu, Yilikal, Alemu, Menbere, Adamu, Liknaw, Dejene, Michael, Mekasha, Addis, Habtamu Jemal, Zelalem, Yadeta, Damtew, Shafi, Oumer, Kiflu, Genet, Willis, Rebecca, Flueckiger, Rebecca M., Chu, Brian K., Pavluck, Alexandre L., and Solomon, Anthony W.

Subjects
TRACHOMA, INFLAMMATION, DISEASE mapping, PUBLIC health, SANITATION
Abstract

Purpose: To complete the baseline trachoma map in Oromia, Ethiopia, by determining prevalences of trichiasis and trachomatous inflammation – follicular (TF) at evaluation unit (EU) level, covering all districts (woredas) without current prevalence data or active control programs, and to identify factors associated with disease. Methods: Using standardized methodologies and training developed for the Global Trachoma Mapping Project, we conducted cross-sectional community-based surveys from December 2012 to July 2014. Results: Teams visited 46,244 households in 2037 clusters from 252 woredas (79 EUs). A total of 127,357 individuals were examined. The overall age- and sex-adjusted prevalence of trichiasis in adults was 0.82% (95% confidence interval, CI, 0.70–0.94%), with 72 EUs covering 240 woredas having trichiasis prevalences above the elimination threshold of 0.2% in those aged ≥15 years. The overall age-adjusted TF prevalence in 1–9-year-olds was 23.4%, with 56 EUs covering 218 woredas shown to need implementation of the A, F and E components of the SAFE strategy (surgery, antibiotics, facial cleanliness and environmental improvement) for 3 years before impact surveys. Younger age, female sex, increased time to the main source of water for face-washing, household use of open defecation, low mean precipitation, low mean annual temperature, and lower altitude, were independently associated with TF in children. The 232 woredas in 64 EUs in which TF prevalence was ≥5% require implementation of the F and E components of the SAFE strategy. Conclusion: Both active trachoma and trichiasis are highly prevalent in much of Oromia, constituting a significant public health problem for the region. [ABSTRACT FROM PUBLISHER]

Published
2016
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44. Resource Planning for Neglected Tropical Disease (NTD) Control Programs: Feasibility Study of the Tool for Integrated Planning and Costing (TIPAC)

Author

Wouters, Olivier J., primary, Downs, Philip W., additional, Zoerhoff, Kathryn L., additional, Crowley, Kathryn R., additional, Frawley, Hannah, additional, Einberg, Jennifer, additional, Chu, Brian K., additional, Brady, Molly A., additional, Oscar, Roland, additional, Jeudi, Mireille, additional, Desormeaux, Anne-Marie, additional, Coly, Karleen, additional, Direny, Abdel N., additional, Thakur, Garib D., additional, Pokharel, Raj K., additional, Sharma, Shekhar, additional, Raman, Dharmpal P., additional, Sesay, Santigie, additional, Sonnie, Mustapha, additional, Kilembe, Bernard, additional, Mwingira, Upendo, additional, and Yajima, Aya, additional

Published
2014
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46. Transmission assessment surveys (TAS) to define endpoints for lymphatic filariasis mass drug administration:a multicenter evaluation

Author

Chu, Brian K., Deming, Michael, Biritwum, Nana-Kwadwo, Bougma, Windtaré R., Dorkenoo, Améyo M., El-Setouhy, Maged, Fischer, Peter U., Gass, Katherine, Peña, Manuel Gonzalez de, Simonsen, Paul Erik, Chu, Brian K., Deming, Michael, Biritwum, Nana-Kwadwo, Bougma, Windtaré R., Dorkenoo, Améyo M., El-Setouhy, Maged, Fischer, Peter U., Gass, Katherine, Peña, Manuel Gonzalez de, and Simonsen, Paul Erik

Abstract

Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached a level low enough that it cannot be sustained even in the absence of drug intervention. Guidelines advanced by WHO call for a transmission assessment survey (TAS) to determine if MDA can be stopped within an LF evaluation unit (EU) after at least five effective rounds of annual treatment. To test the value and practicality of these guidelines, a multicenter operational research trial was undertaken in 11 countries covering various geographic and epidemiological settings.

Published
2013

47. Transmission Assessment Surveys (TAS) to Define Endpoints for Lymphatic Filariasis Mass Drug Administration: A Multicenter Evaluation

Author

Chu, Brian K., primary, Deming, Michael, additional, Biritwum, Nana-Kwadwo, additional, Bougma, Windtaré R., additional, Dorkenoo, Améyo M., additional, El-Setouhy, Maged, additional, Fischer, Peter U., additional, Gass, Katherine, additional, Gonzalez de Peña, Manuel, additional, Mercado-Hernandez, Leda, additional, Kyelem, Dominique, additional, Lammie, Patrick J., additional, Flueckiger, Rebecca M., additional, Mwingira, Upendo J., additional, Noordin, Rahmah, additional, Offei Owusu, Irene, additional, Ottesen, Eric A., additional, Pavluck, Alexandre, additional, Pilotte, Nils, additional, Rao, Ramakrishna U., additional, Samarasekera, Dilhani, additional, Schmaedick, Mark A., additional, Settinayake, Sunil, additional, Simonsen, Paul E., additional, Supali, Taniawati, additional, Taleo, Fasihah, additional, Torres, Melissa, additional, Weil, Gary J., additional, and Won, Kimberly Y., additional

Published
2013
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50. A Tail of Two Peptide Amphiphiles: Effect of Conjugationwith Hydrophobic Polymer on Folding of Peptide Sequences.

Author

Chu, Brian K., Fu, Iris W., Markegard, Cade B., Choi, Seong E., and Nguyen, Hung D.

Subjects
*PEPTIDE amphiphiles, *BIOCONJUGATES, *PROTEIN folding, *AMINO acid sequence, *TISSUE engineering, *REGENERATIVE medicine, *NANOFIBERS
Abstract

Peptide amphiphiles (PA) offer thepotential of incorporating biologicalfunction into synthetic materials for tissue engineering in regenerativemedicine. These hybrid conjugates are known to undergo self-assemblystarting from single molecules to nanofibers before turning into hydrogelscaffoldssuch a process involves conformational changes insecondary structures of peptides. Therefore, insights on the abilityof peptide amphiphiles to form secondary structure as single moleculesare useful for understanding self-assembly behavior. We report herea molecular simulation study of peptide folding by two PA sequences,each contains an alkyl tail and short peptide segment. The alkyl tailis observed to play two opposing roles in modulating sequence-dependentfolding kinetics and thermodynamics. On one hand, it restricts conformationalfreedom reducing the entropic cost of folding, which is thus promoted.On the other hand, it acts as an interaction site with nonpolar peptideresidues, blocking the peptide from helix nucleation, which reducesfolding. [ABSTRACT FROM AUTHOR]

Published
2014
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