354 results on '"Mabey, David C W"'
Search Results
2. Oral doxycycline for the prevention of postoperative trachomatous trichiasis in Ethiopia: a randomised, double-blind, placebo-controlled trial
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Habtamu, Esmael, Wondie, Tariku, Aweke, Sintayehu, Tadesse, Zerihun, Zerihun, Mulat, Gashaw, Bizuayehu, Roberts, Chrissy H, Kello, Amir Bedri, Mabey, David C W, Rajak, Saul N, Callahan, E Kelly, Macleod, David, Weiss, Helen A, and Burton, Matthew J
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- 2018
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3. Comparative efficacy of low-dose versus standard-dose azithromycin for patients with yaws: a randomised non-inferiority trial in Ghana and Papua New Guinea
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Marks, Michael, Mitjà, Oriol, Bottomley, Christian, Kwakye, Cynthia, Hounei, Wendy, Bauri, Mathias, Adwere, Paul, Abdulai, Abdul A, Dua, Fredrick, Boateng, Laud, Wangi, James, Ohene, Sayy-Ann, Wangnapi, Regina, Simpson, Shirley V, Miag, Helen, Addo, Kennedy K, Basing, Laud A, Danavall, Damien, Chi, Kai H, Pillay, Allan, Ballard, Ronald, Solomon, Anthony W, Chen, Cheng Y, Bieb, Sivuak V, Adu-Sarkodie, Yaw, Mabey, David CW, Asiedu, Kingsley, Agana, Nsire, Ampadu, Edwin, Amponsah-Achiano, Kwame, Bediako, Asare, Biredu, Michael, Faried, Kyei, Iddrisu, Ahmed, Kotey, Nana K, Yeboah, George NY, El-Duah, Philip, Phillips, Richard, Binka, Fred, Nyonator, Frank, Zunuo, Anthony, Ackumey, Mercy A, Amanor, Ivy, Bnosu, Christian, Frischmann, Sieghard, Lammie, Patrick, Martin, Diana, Ye, Tun, Christophel, Eva, Tiendrebeogo, Alexandre, Vestergard, Lasse, Bassat, Quique, Abdad, Yazid, Dima, Henson, Kotty, Bethuel, Mamore, Kaiok, Manup, Walerius, Olowau, Benson, Agyei, Enoch O, Agyemang, David, Ako, Ebenezer P, Antwi, Prince, Darko, Jane, Darko, Ophelia O, Darko, Phylis, Duodu, Bertha, Jabasi, Daniel, Karim, Fuseini L, Koomson, Obed K, Labri, Bernard A, Nartey, John, Tamatey, Randsford, Yirenkyi, Benjamin, Arhin, Mercy, Biney, Frank, Danso, Juliana O, Dei, Martin A, Djan, Moses, Sasu, Samuel, Solomon, Brefo A, Torvinya, Victor, Amankwaah, Hagar, Baffoe, James, Keteku, Lydia, Kondobala, Kofi, Lomotey, Rita D, Nartey, Augustina A, Oppong, Paul, Quainoo, Millicent A, Abotsi, Theophilus, Agebshie, Dzighordi, Ameamu, Amos, Angwaawie, Paul, Ayibor, Rose, Mwingmendeli, Margaret, Nakodia, John, Nambagyira, Amatus, Nanga, Dominic, Tetteh, Nichola, Wanaom, Augustine, Houinei, Wendy, Ohene, Sally-Ann, Bieb, Sibauk V, and Mabey, David C W
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- 2018
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4. Diagnostics for Yaws Eradication : Insights From Direct Next-Generation Sequencing of Cutaneous Strains of Treponema pallidum
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Marks, Michael, Fookes, Maria, Wagner, Josef, Butcher, Robert, Ghinai, Rosanna, Sokana, Oliver, Sarkodie, Yaw-Adu, Lukehart, Sheila A., Solomon, Anthony W., Mabey, David C. W., and Thomson, Nicholas
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- 2018
5. Facial cleanliness indicators by time of day: results of a cross-sectional trachoma prevalence survey in Senegal
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Harding-Esch, Emma M., Holland, Martin J., Schémann, Jean-François, Sissoko, Mactar, Sarr, Boubacar, Butcher, Robert M. R., Molina-Gonzalez, Sandra, Andreasen, Aura A., Mabey, David C. W., and Bailey, Robin L.
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- 2020
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6. Posterior lamellar versus bilamellar tarsal rotation surgery for trachomatous trichiasis in Ethiopia: a randomised controlled trial
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Habtamu, Esmael, Wondie, Tariku, Aweke, Sintayehu, Tadesse, Zerihun, Zerihun, Mulat, Zewudie, Zebideru, Kello, Amir Bedri, Roberts, Chrissy H, Emerson, Paul M, Bailey, Robin L, Mabey, David C W, Rajak, Saul N, Callahan, Kelly, Weiss, Helen A, and Burton, Matthew J
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- 2016
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7. Impact of a single round of mass drug administration with azithromycin on active trachoma and ocular Chlamydia trachomatis prevalence and circulating strains in The Gambia and Senegal
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Harding-Esch, Emma M., Holland, Martin J., Schémann, Jean-François, Sillah, Ansumana, Sarr, Boubacar, Christerson, Linus, Pickering, Harry, Molina-Gonzalez, Sandra, Sarr, Isatou, Andreasen, Aura A., Jeffries, David, Grundy, Chris, Mabey, David C. W., Herrmann, Bjorn, and Bailey, Robin L.
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- 2019
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8. Challenges and key research questions for yaws eradication
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Marks, Michael, Mitjà, Oriol, Vestergaard, Lasse S, Pillay, Allan, Knauf, Sascha, Chen, Cheng-Yen, Bassat, Quique, Martin, Diana L, Fegan, David, Taleo, Fasihah, Kool, Jacob, Lukehart, Sheila, Emerson, Paul M, Solomon, Anthony W, Ye, Tun, Ballard, Ronald C, Mabey, David C W, and Asiedu, Kingsley B
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- 2015
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9. Perceptions and acceptability of co-administered albendazole, ivermectin and azithromycin mass drug administration, among the health workforce and recipient communities in Ethiopia.
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McPherson, Scott, Geleta, Dereje, Tafese, Getinet, Tafese, Temesgen, Behaksira, Sinkinesh, Solomon, Hiwot, Oljira, Birhanu, Miecha, Hirpa, Gemechu, Lalisa, Debebe, Kaleab, Kebede, Biruck, Gebre, Teshome, Kebede, Fikreab, Seife, Fikre, Tadesse, Fentahun, Mammo, Belete, Aseffa, Abraham, Solomon, Anthony W., Mabey, David C. W., and Marks, Michael
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MEDICAL personnel ,DRUG administration ,COMMUNITY health workers ,NEGLECTED diseases ,IVERMECTIN ,DRUG formularies - Abstract
Several neglected tropical diseases (NTDs) employ mass drug administration (MDA) as part of their control or elimination strategies. This has historically required multiple distinct campaigns, each targeting one or more NTDs, representing a strain on both the recipient communities and the local health workforce implementing the distribution. We explored perceptions and attitudes surrounding combined MDA among these two groups of stakeholders. Our qualitative study was nested within a cluster randomized non-inferiority safety trial of combined ivermectin, albendazole and azithromycin MDA. Using semi-structured question guides, we conducted 16 key informant interviews with selected individuals involved in implementing MDA within the participating district. To better understand the perceptions of recipient communities, we also conducted four focus group discussions with key community groups. Individuals were selected from both the trial arm (integrated MDA) and the control arm (standard MDA) to provide a means of comparison and discussion. All interviews and focus group discussions were led by fluent Afaan oromo speakers. Interviewers transcribed and later translated all discussions into English. The study team synthesized and analyzed the results via a coding framework and software. Most respondents appreciated the time and effort saved via the co-administered MDA strategy but there were some misgivings amongst community beneficiaries surrounding pill burden. Both the implementing health work force members and beneficiaries reported refusals stemming from lack of understanding around the need for the new drug regimen as well as some mistrust of government officials among the youth. The house-to-house distribution method, adopted as a COVID-19 prevention strategy, was by far preferred by all beneficiaries over central-point MDA, and may have led to greater acceptability of co-administration. Our data demonstrate that a co-administration strategy for NTDs is acceptable to both communities and health staff. Author summary: The strategy for several neglected tropical diseases is treatment of the whole community, referred to as mass drug administration. Normally these are delivered as separate rounds of treatment for each disease. This creates a burden for both the health workforce and the communities. As part of a larger study conducted in Ethiopia we used interviews and focus groups to explore perceptions and attitudes towards combined mass drug administration among both communities and health workers. Both community members and health workers appreciated the time and effort saved via combined treatment although some community members were worried about the number of pills that had to be taken. Both health workers and community members said some people declined to take part due to a lack of understanding around the need for a combined drug regimen. Delivery of the drugs house-to-house, which had been adopted as a COVID-19 prevention strategy, was preferred over delivering the treatment at a central point in the community. Overall, our study showed that combined treatment of multiple neglected tropical diseases was acceptable to both communities and health workers. [ABSTRACT FROM AUTHOR]
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- 2023
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10. Differential frequency of NKG2C/KLRC2 deletion in distinct African populations and susceptibility to Trachoma: a new method for imputation of KLRC2 genotypes from SNP genotyping data
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Goncalves, Adriana, Makalo, Pateh, Joof, Hassan, Burr, Sarah, Ramadhani, Athumani, Massae, Patrick, Malisa, Aiweda, Mtuy, Tara, Derrick, Tamsyn, Last, Anna R., Nabicassa, Meno, Cassama, Eunice, Houghton, Joanna, Palmer, Christine D., Pickering, Harry, Burton, Matthew J., Mabey, David C. W., Bailey, Robin L., Goodier, Martin R., Holland, Martin J., and Roberts, Chrissy h.
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- 2016
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11. Impact of Acyclovir on Genital and Plasma HIV-1 RNA, Genital Herpes Simplex Virus Type 2 DNA, and Ulcer Healing among HIV-1–Infected African Women with Herpes Ulcers: A Randomized Placebo-Controlled Trial
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Mayaud, Philippe, LeGoff, Jérôme, Weiss, Helen A., Grésenguet, Gérard, Nzambi, Khonde, Bouhlal, Hicham, Frost, Eric, Pépin, Jacques, Malkin, Jean-Elie, Hayes, Richard J., Mabey, David C. W., and Bélec, Laurent
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- 2009
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12. Pathogenic Diversity among Chlamydia trachomatis Ocular Strains in Nonhuman Primates Is Affected by Subtle Genomic Variations
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Kari, Laszlo, Whitmire, William M., Carlson, John H., Crane, Deborah D., Reveneau, Nathalie, Nelson, David E., Mabey, David C. W., Bailey, Robin L., Holland, Martin J., McClarty, Grant, and Caldwell, Harlan D.
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- 2008
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13. Pharmacokinetics, feasibility and safety of co-administering azithromycin, albendazole, and ivermectin during mass drug administration: A review.
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McPherson, Scott, Solomon, Anthony W., Seife, Fikre, Solomon, Hiwot, Gebre, Teshome, Mabey, David C. W., and Marks, Michael
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IVERMECTIN ,ALBENDAZOLE ,DRUG administration ,AZITHROMYCIN ,PHARMACOKINETICS - Abstract
Introduction: Traditionally, health ministries implement mass drug administration programmes for each neglected tropical disease (NTD) as separate and distinct campaigns. Many NTDs have overlapping endemicity suggesting co-administration might improve programme reach and efficiency, helping accelerate progress towards 2030 targets. Safety data are required to support a recommendation to undertake co-administration. Methodology: We aimed to compile and summarize existing data on co-administration of ivermectin, albendazole and azithromycin, including both data on pharmacokinetic interactions and data from previous experimental and observational studies conducted in NTD-endemic populations. We searched PubMed, Google Scholar, research and conference abstracts, gray literature, and national policy documents. We limited the publication language to English and used a search period from January 1
st , 1995 through October 1st , 2022. Search terms were: azithromycin and ivermectin and albendazole, mass drug administration co-administration trials, integrated mass drug administration, mass drug administration safety, pharmacokinetic dynamics, and azithromycin and ivermectin and albendazole. We excluded papers if they did not include data on co-administration of azithromycin and both albendazole and ivermectin, or azithromycin with either albendazole or ivermectin alone. Results: We identified a total of 58 potentially relevant studies. Of these we identified 7 studies relevant to the research question and which met our inclusion criteria. Three papers analyzed pharmacokinetic and pharmacodynamic interactions. No study found evidence of clinically significant drug-drug interactions likely to impact safety or efficacy. Two papers and a conference presentation reported data on the safety of combinations of at least two of the drugs. A field study in Mali suggested the rates of adverse events were similar with combined or separate administration, but was underpowered. A further field study in Papua New Guinea used all three drugs as part of a four-drug regimen also including diethylcarbamazine; in this setting, co-administration appeared safe but there were issues with the consistency in how adverse events were recorded. Conclusion: There are relatively limited data on the safety profile of co-administering ivermectin, albendazole and azithromycin as an integrated regimen for NTDs. Despite the limited amount of data, available evidence suggests that such a strategy is safe with an absence of clinically important drug-drug interactions, no serious adverse events reported and little evidence for an increase in mild adverse events. Integrated MDA may be a viable strategy for national NTD programmes. Author summary: Treatment of the whole community (mass drug administration, MDA) has been a major intervention strategy against many neglected tropical diseases (NTDs) over the last decade. Normally health ministries deliver individual MDA rounds targeting specific NTDs. This multiplies the training, transport and time burden for local health service personnel in districts in which several NTDs are present, imposing considerable financial and human resource costs to health ministries and their partners, and causing requiring repeated disruption to the daily life of communities receiving MDA. Delivering MDA for several NTDs at one time could improve the efficiency of NTD programmes. We reviewed existing data on the safety and feasibility of combining MDA of albendazole, ivermectin and azithromycin into a single co-delivered MDA. Several studies had evaluated if taking these drugs at the same time changed drug levels in recipients' blood; these studies concluded that there was not an important difference in blood drug levels comparing instances when the medicines were taken separately to instances when they were taken at the same time. Two non-randomised studies assessed side effects experienced by people taking combinations of the three drugs and suggested doing so was safe. One small study in Mali had assessed combining all three drugs and also suggested this was safe but was too small to give a definitive answer. Two studies in Papua New Guinea assessed all three drugs being taken together in combination with a fourth drug, diethylcarbamazine. These studies also suggest co-administration was safe overall. Most of the identified studies had some methodological shortcomings, such as small sample sizes or issues with the way adverse events were recorded. Overall, the data suggest co-administration of azithromycin, ivermectin and albendazole is viable, but larger safety studies are needed. [ABSTRACT FROM AUTHOR]- Published
- 2023
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14. A systems serology approach to the investigation of infection-induced antibody responses and protection in trachoma.
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Barton, Amber, Rosenkrands, Ida, Pickering, Harry, Faal, Nkoyo, Harte, Anna, Joof, Hassan, Makalo, Pateh, Ragonnet, Manon, Olsen, Anja Weinreich, Bailey, Robin L., Mabey, David C. W., Follmann, Frank, Dietrich, Jes, and Holland, Martin J.
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ANTIBODY formation ,SEROLOGY ,TRACHOMA ,NEGLECTED diseases ,MEMBRANE proteins - Abstract
Background: Ocular infections with Chlamydia trachomatis serovars A-C cause the neglected tropical disease trachoma. As infection does not confer complete immunity, repeated infections are common, leading to long-term sequelae such as scarring and blindness. Here, we apply a systems serology approach to investigate whether systemic antibody features are associated with susceptibility to infection. Methods: Sera from children in five trachoma endemic villages in the Gambia were assayed for 23 antibody features: IgG responses towards two C. trachomatis antigens and three serovars [elementary bodies and major outer membrane protein (MOMP), serovars A-C], IgG responses towards five MOMP peptides (serovars A-C), neutralization, and antibody-dependent phagocytosis. Participants were considered resistant if they subsequently developed infection only when over 70% of other children in the same compound were infected. Results: The antibody features assayed were not associated with resistance to infection (false discovery rate < 0.05). Anti-MOMP SvA IgG and neutralization titer were higher in susceptible individuals (p < 0.05 before multiple testing adjustment). Classification using partial least squares performed only slightly better than chance in distinguishing between susceptible and resistant participants based on systemic antibody profile (specificity 71%, sensitivity 36%). Conclusions: Systemic infection-induced IgG and functional antibody responses do not appear to be protective against subsequent infection. Ocular responses, IgA, avidity, or cell-mediated responses may play a greater role in protective immunity than systemic IgG. [ABSTRACT FROM AUTHOR]
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- 2023
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15. Polymorphisms in Candidate Genes and Risk of Scarring Trachoma in a Chlamydia trachomatis-Endemic Population
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Mozzato-Chamay, Nadia, Mahdi, Olaimatu S. M., Jallow, Ousman, Mabey, David C. W., Bailey, Robin L., and Conway, David J.
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- 2000
16. Interactions between Herpes Simplex Virus Type 2 and Human Immunodeficiency Virus Type 1 Infection in African Women: Opportunities for Intervention
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Mbopi-Kéou, François-Xavier, Grésenguet, Gérard, Mayaud, Philippe, Weiss, Helen A., Gopal, Robin, Matta, Mathieu, Paul, Jean-Louis, Brown, David W. G., Hayes, Richard J., Mabey, David C. W., and Bélec, Laurent
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- 2000
17. Antibody Response to the 60-kDa Chlamydial Heat-Shock Protein Is Associated with Scarring Trachoma
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Peeling, Rosanna W., Bailey, Robin L., Conway, David J., Holland, Martin J., Campbell, Alison E., Jallow, Ousman, Whittle, Hilton C., and Mabey, David C. W.
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- 1998
18. HLA Class I and II Polymorphisms and Trachomatous Scarring in a Chlamydia trachomatis-Endemic Population
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Conway, David J., Holland, Martin J., Campbell, Alison E., Bailey, Robin L., Krausa, Peter, Peeling, Rosanna W., Whittle, Hilton C., and Mabey, David C. W.
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- 1996
19. Effect of azithromycin mass drug administration for trachoma on spleen rates in Gambian children
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Hart, John D., Edwards, Tansy, Burr, Sarah E., Harding-Esch, Emma M., Takaoka, Kensuke, Holland, Martin J., Sillah, Ansumana, Mabey, David C. W., and Bailey, Robin L.
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- 2014
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20. In vivo confocal microscopy and histopathology of the conjunctiva in trachomatous scarring and normal tissue: a systematic comparison
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Hu, Victor H, Holland, Martin J, Cree, Ian A, Pullin, James, Weiss, Helen A, Massae, Patrick, Makupa, William, Mabey, David C W, Bailey, Robin L, Burton, Matthew J, and Luthert, Phil
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- 2013
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21. Using a Nonparametric Multilevel Latent Markov Model to Evaluate Diagnostics for Trachoma
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Koukounari, Artemis, Moustaki, Irini, Grassly, Nicholas C., Blake, Isobel M., Basáñez, María-Gloria, Gambhir, Manoj, Mabey, David C. W., Bailey, Robin L., Burton, Matthew J., Solomon, Anthony W., and Donnelly, Christl A.
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- 2013
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22. Epidemiology and control of trachoma: systematic review
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Hu, Victor H., Harding-Esch, Emma M., Burton, Matthew J., Bailey, Robin L., Kadimpeul, Julbert, and Mabey, David C. W.
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- 2010
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23. Absence of Mycoplasma genitalium in eye samples from a trachoma-endemic area of Tanzania
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Pepin, Jacques, Deslandes, Sylvie, Frost, Eric, Andreassen, Aura Aguirre, Solomon, Anthony W, Bailey, Robin, and Mabey, David C W
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- 2008
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24. Progression of scarring trachoma in Tanzanian children: A four-year cohort study
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Ramadhani, Athumani M., Derrick, Tamsyn, Macleod, David, Massae, Patrick, Mafuru, Elias, Malisa, Aiweda, Mbuya, Kelvin, Roberts, Chrissy h., Makupa, William, Mtuy, Tara, Bailey, Robin L., Mabey, David C. W., Holland, Martin J., and Burton, Matthew J.
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Bacterial Diseases ,Male ,Eye Diseases ,RC955-962 ,Chlamydia trachomatis ,Pathology and Laboratory Medicine ,Tanzania ,Chlamydia Infection ,Cohort Studies ,Families ,Risk Factors ,Arctic medicine. Tropical medicine ,Medicine and Health Sciences ,Odds Ratio ,Longitudinal Studies ,Chlamydia ,Child ,Immune Response ,Children ,Incidence ,Bacterial Pathogens ,Infectious Diseases ,Medical Microbiology ,Research Design ,Disease Progression ,Female ,Public aspects of medicine ,RA1-1270 ,Pathogens ,Conjunctiva ,Research Article ,Neglected Tropical Diseases ,Inflammatory Diseases ,Immunology ,Sexually Transmitted Diseases ,Research and Analysis Methods ,Microbiology ,Cicatrix ,Signs and Symptoms ,Diagnostic Medicine ,Humans ,Microbial Pathogens ,Trachoma ,Inflammation ,Bacteria ,Organisms ,Biology and Life Sciences ,Tropical Diseases ,Ophthalmology ,Age Groups ,People and Places ,Population Groupings - Abstract
Background Trachoma is a progressive blinding disease initiated by infection of the conjunctiva with Chlamydia trachomatis. Repeated infections are thought to cause chronic inflammation, which drives scarring, leading to in-turning of the eyelids. The relationship between C. trachomatis, clinical inflammation and scarring development in children is not fully understood due to a paucity of longitudinal studies with infection data at frequent follow-up. Methods and findings This longitudinal cohort study took place in northern Tanzania. Children aged 6–10 years at baseline were eligible for inclusion. Participants were visited every three months for four years. Clinical signs and conjunctival swabs for C. trachomatis detection by qPCR were collected at each time-point. Conjunctival photographs from baseline and final time-points were graded and compared side-by-side to determine scarring incidence and progression. Of the 666 children enrolled in the study, outcome data were obtained for 448. Scarring progression was detected in 103/448 (23%) children; 48 (11%) of which had incident scarring and 55 (12%) had progression of existing scarring. Scarring was strongly associated with increasing episodes of trachomatous papillary inflammation (TP). Weaker associations were found between episodes of C. trachomatis infection and follicular trachoma (TF) with scarring progression in unadjusted models, which were absent in multivariable analysis after adjusting for inflammation (multivariable results: C. trachomatis p = 0.44, TF p = 0.25, TP p =, Author summary Trachoma is the leading cause of preventable blindness worldwide and is targeted for elimination as a public health problem by 2020. The natural history of trachoma is not completely understood however. We conducted a four-year longitudinal study in a trachoma-endemic area of northern Tanzania with detailed follow up every three months. In the four-year study period, nearly one quarter of children developed progression of conjunctival scarring, despite three rounds of annual mass drug administration (MDA) for trachoma control. Disease progression was strongly associated with increasing proportion of episodes with conjunctival papillary inflammation (TP), and only weakly associated with Chlamydia trachomatis infection and trachomatous inflammation–follicular (TF). Analysis revealed that associations between infection and TF with scarring progression were mediated through TP, and that other factors causing individual differences in TP were also contributing to scarring progression. These data have significant implications for trachoma control. We hypothesise that in individuals who have previously experienced ocular C. trachomatis infection, TP is the primary driver of scarring progression. The addition of TP to trachoma surveillance programs would provide an indicator for active disease progression in the community and a more accurate guide to the need for future trichiasis interventions.
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- 2019
25. Ocular immune responses, Chlamydia trachomatis infection and clinical signs of trachoma before and after azithromycin mass drug administration in a treatment naïve trachoma-endemic Tanzanian community
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Ramadhani, Athumani M., Derrick, Tamsyn, Macleod, David, Massae, Patrick, Malisa, Aiweda, Mbuya, Kelvin, Mtuy, Tara, Makupa, William, Roberts, Chrissy H., Bailey, Robin L., Mabey, David C. W., Holland, Martin J., and Burton, Matthew J.
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Bacterial Diseases ,Male ,Eye Diseases ,RC955-962 ,Gene Expression ,Chlamydia trachomatis ,Azithromycin ,Pathology and Laboratory Medicine ,Blindness ,Tanzania ,Chlamydia Infection ,Cohort Studies ,Families ,Arctic medicine. Tropical medicine ,Medicine and Health Sciences ,Prevalence ,Chlamydia ,Child ,Immune Response ,Children ,Bacterial Pathogens ,Anti-Bacterial Agents ,Infectious Diseases ,Medical Microbiology ,Mass Drug Administration ,Female ,Public aspects of medicine ,RA1-1270 ,Pathogens ,Anatomy ,Conjunctiva ,Research Article ,Neglected Tropical Diseases ,Inflammatory Diseases ,Immunology ,Sexually Transmitted Diseases ,Microbiology ,Cicatrix ,Signs and Symptoms ,Diagnostic Medicine ,Ocular System ,Genetics ,Humans ,Microbial Pathogens ,Trachoma ,Inflammation ,Bacteria ,Organisms ,Biology and Life Sciences ,Chlamydia Infections ,Tropical Diseases ,Ophthalmology ,Logistic Models ,Age Groups ,People and Places ,Linear Models ,Eyes ,Population Groupings ,Head - Abstract
Background Trachoma, caused by Chlamydia trachomatis, remains the leading infectious cause of blindness worldwide. Persistence and progression of the resulting clinical disease appears to be an immunologically mediated process. Azithromycin, which is distributed at the community level for trachoma control, has immunomodulatory properties. We investigated the impact of one round of oral azithromycin on conjunctival immune responses, C. trachomatis infection and clinical signs three- and six- months post treatment relative to three pre-treatment time-points. Methodology A cohort of children aged 6 to 10 years were recruited from a trachoma endemic region of northern Tanzania and were visited five times in a 12-month period. They were examined for clinical signs of trachoma and conjunctival swabs were collected for laboratory analysis. C. trachomatis infection was detected and the expression of 46 host genes was quantified using quantitative PCR. All community members were offered azithromycin treatment immediately after the six-month timepoint according to international guidelines. Findings The prevalence of C. trachomatis infection and inflammatory disease signs were significantly reduced three- and six- months post-mass drug administration (MDA). C. trachomatis infection was strongly associated with clinical signs at all five time-points. A profound anti-inflammatory effect on conjunctival gene expression was observed 3 months post-MDA, however, gene expression had largely returned to pre-treatment levels of variation by 6 months. This effect was less marked, but still observed, after adjusting for C. trachomatis infection and when the analysis was restricted to individuals who were free from both infection and clinical disease at all five time-points. Interestingly, a modest effect was also observed in individuals who did not receive treatment. Conclusion Conjunctival inflammation is the major clinical risk factor for progressive scarring trachoma, therefore, the reduction in inflammation associated with azithromycin treatment may be beneficial in limiting the development of potentially blinding disease sequelae. Future work should seek to determine whether this effect is mediated directly through inhibition of pro-inflammatory intracellular signalling molecules, through reductions in concurrent, sub-clinical infections, and/or through reduction of infection exposure., Author summary Trachoma, caused by conjunctival infection with Chlamydia trachomatis, remains the leading infectious cause of blindness. Repeated infection during childhood can trigger prolonged inflammation, which is the main risk factor for conjunctival scarring. Azithromycin is distributed globally for trachoma control, however it is also widely reported to have immunomodulatory properties. This report investigated the impact of one round of oral azithromycin for trachoma control on conjunctival immune responses, clinical signs and C. trachomatis infection in Tanzanian children. A large anti-inflammatory effect of azithromycin on conjunctival gene expression was observed 3 months post-treatment, however, gene expression patterns had mostly resumed to pre-treatment levels by 6 months. The effect was evident after adjusting for C. trachomatis infection and when analysis was restricted to uninfected individuals, however it was also observed to a lesser extent in individuals that did not receive treatment. These findings suggest that azithromycin may have a direct immunomodulatory effect on conjunctival gene expression but that it may also reduce inflammation by reducing exposure to C. trachomatis and other infections. This anti-inflammatory effect could have therapeutic potential in limiting the development of disease sequelae, that goes beyond its effect on the clearance of ocular C. trachomatis infection.
- Published
- 2019
26. Prevalence of HIV and Chlamydia trachomatis infection in 15–19-year olds in rural Tanzania
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Obasi, Angela I., Balira, Rebecca, Todd, Jim, Ross, David A., Changalucha, John, Mosha, Frank, Grosskurth, Heiner, Peeling, Rosanna, Mabey, David C. W., and Hayes, Richard J.
- Published
- 2001
27. POLYMORPHISMS IN CANDIDATE GENES INVOLVED IN THE DEVELOPMENT OF SCARRING TRACHOMA
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Chamay, Nadia Mozzato, Mahdi, Olaimatu S. M., Mabey, David C. W., Bailey, Robin L., and Conway, David J.
- Published
- 1999
28. Targeted treatment of yaws with contact tracing : how much do we miss?\ud \ud
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Dyson, Louise, Marks, Michael, Crook, Oliver M., Sokana, Oliver, Solomon, Anthony W., Bishop, Alex, Mabey, David C. W., and Hollingsworth, T. Déirdre
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RC - Abstract
Yaws is a disabling bacterial infection found primarily in warm and humid tropical areas. The World Health Organization strategy mandates an initial round of total community treatment (TCT) with single-dose azithromycin followed either by further TCT or active case-finding and treatment of cases and their contacts (the Morges strategy). We sought to investigate the effectiveness of the Morges strategy. We employed a stochastic household model to study the transmission of infection using data collected from a pre-TCT survey conducted in the Solomon Islands. We used this model to assess the proportion of asymptomatic infections that occurred in households without active cases. This analysis indicated that targeted treatment of cases and their household contacts would miss a large fraction of asymptomatic infections (65%–100%). This fraction was actually higher at lower prevalences. Even assuming that all active cases and their households were successfully treated, our analysis demonstrated that at all prevalences present in the data set, up to 90% of (active and asymptomatic) infections would not be treated under household-based contact tracing. Mapping was undertaken as part of the study “Epidemiology of Yaws in the Solomon Islands and the Impact of a Trachoma Control Programme,” in September–October 2013.
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- 2018
29. Emergency Department Presentation and Misdiagnosis of Imported Falciparum Malaria
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Kyriacou, Demetrios N, Spira, Alan M, Talan, David A, and Mabey, David C W
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- 1996
30. Diagnostics for Yaws Eradication: Insights From Direct Next-Generation Sequencing of Cutaneous Strains of Treponema pallidum
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Marks, Michael, Fookes, Maria, Wagner, Josef, Butcher, Robert, Ghinai, Rosanna, Sokana, Oliver, Sarkodie, Yaw-Adu, Lukehart, Sheila A, Solomon, Anthony W, Mabey, David C W, and Thomson, Nicholas
- Subjects
Male ,genetic structures ,Whole Genome Sequencing ,yaws ,High-Throughput Nucleotide Sequencing ,Sequence Analysis, DNA ,Real-Time Polymerase Chain Reaction ,Ghana ,body regions ,Molecular Diagnostic Techniques ,whole-genome sequencing ,Skin Ulcer ,Humans ,next-generation sequencing ,Female ,Treponema pallidum ,Melanesia ,Disease Eradication ,skin and connective tissue diseases ,Child ,Articles and Commentaries ,Genome, Bacterial - Abstract
Yaws is an important cause of skin disease in tropical countries. Using next-generation sequencing, we tested yaws-like ulcers, which were negative using standard molecular diagnostics. We found primer binding site mutations explaining the negative results of the standard assay., Background Yaws-like chronic ulcers can be caused by Treponema pallidum subspecies pertenue, Haemophilus ducreyi, or other, still-undefined bacteria. To permit accurate evaluation of yaws elimination efforts, programmatic use of molecular diagnostics is required. The accuracy and sensitivity of current tools remain unclear because our understanding of T. pallidum diversity is limited by the low number of sequenced genomes. Methods We tested samples from patients with suspected yaws collected in the Solomon Islands and Ghana. All samples were from patients whose lesions had previously tested negative using the Centers for Disease Control and Prevention (CDC) diagnostic assay in widespread use. However, some of these patients had positive serological assays for yaws on blood. We used direct whole-genome sequencing to identify T. pallidum subsp pertenue strains missed by the current assay. Results From 45 Solomon Islands and 27 Ghanaian samples, 11 were positive for T. pallidum DNA using the species-wide quantitative polymerase chain reaction (PCR) assay, from which we obtained 6 previously undetected T. pallidum subsp pertenue whole-genome sequences. These show that Solomon Islands sequences represent distinct T. pallidum subsp pertenue clades. These isolates were invisible to the CDC diagnostic PCR assay, due to sequence variation in the primer binding site. Conclusions Our data double the number of published T. pallidum subsp pertenue genomes. We show that Solomon Islands strains are undetectable by the PCR used in many studies and by health ministries. This assay is therefore not adequate for the eradication program. Next-generation genome sequence data are essential for these efforts.
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- 2017
31. Neurosyphilis in Africa: A systematic review
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Marks, Michael, Jarvis, Joseph N., Howlett, William, and Mabey, David C. W.
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Bacterial Diseases ,lcsh:Arctic medicine. Tropical medicine ,lcsh:RC955-962 ,Physiology ,Urology ,Inflammatory Diseases ,Cerebrovascular Diseases ,Sexually Transmitted Diseases ,HIV Infections ,Nervous System ,Vascular Medicine ,Treponematoses ,Geographical Locations ,Infectious Diseases of the Nervous System ,Diagnostic Medicine ,Neurosyphilis ,Medicine and Health Sciences ,Humans ,Meningitis ,Syphilis ,Cerebrospinal Fluid ,Genitourinary Infections ,Coinfection ,lcsh:Public aspects of medicine ,Biology and Life Sciences ,lcsh:RA1-1270 ,HIV diagnosis and management ,Tropical Diseases ,Body Fluids ,Stroke ,Infectious Diseases ,Neurology ,People and Places ,Africa ,HIV clinical manifestations ,Anatomy ,Research Article ,Neglected Tropical Diseases - Abstract
Introduction Neurological involvement is one of the most important clinical manifestations of syphilis and neurological disease occurs in both early and late syphilis. The impact of HIV co-infection on clinical neurosyphilis remains unclear. The highest prevalence of both syphilis and HIV is in Africa. Therefore it might be expected that neurosyphilis would be an important and not uncommon manifestation of syphilis in Africa and frequently occur in association with HIV co-infection; yet few data are available on neurosyphilis in Africa. The aim of this study is to review data on neurosyphilis in Africa since the onset of the HIV epidemic. Methods We searched the literature for references on neurosyphilis in Africa for studies published between the 1st of January 1990 and 15th February 2017. We included case reports, case series, and retrospective and prospective cohort and case-control studies. We did not limit inclusion based on the diagnostic criteria used for neurosyphilis. For retrospective and prospective cohorts, we calculated the proportion of study participants who were diagnosed with neurosyphilis according to the individual study criteria. Depending on the study, we assessed the proportion of patients with syphilis found to have neurosyphilis, and the proportion of patients with neurological syndromes who had neurosyphilis. Due to heterogeneity of data no formal pooling of the data or meta-analysis was undertaken. Results Amongst patients presenting with a neurological syndrome, three studies of patients with meningitis were identified; neurosyphilis was consistently reported to cause approximately 3% of all cases. Three studies on stroke reported mixed findings but were limited due to the small number of patients undergoing CSF examination, whilst neurosyphilis continued to be reported as a common cause of dementia in studies from North Africa. Ten studies reported on cases of neurosyphilis amongst patients known to have syphilis. Studies from both North and Southern Africa continue to report cases of late stage syphilis, including tabes dorsalis and neurosyphilis, in association with ocular disease. Discussion This is the first systematic review of the literature on neurosyphilis in Africa since the beginning of the HIV epidemic. Neurosyphilis continues to be reported as a manifestation of both early and late syphilis, but the methodological quality of the majority of the included studies was poor. Future well-designed prospective studies are needed to better delineate the incidence and clinical spectrum of neurosyphilis in Africa and to better define interactions with HIV in this setting., Author summary Involvement of the central nervous system is an important manifestation of syphilis which may be more common in patients co-infected with HIV. As most cases of syphilis and HIV are seen in Africa it might be anticipated that neurosyphilis was common there. We reviewed all published material on neurosyphilis in Africa since 1990. There were few well designed studies of neurosyphilis. A small number of studies suggested that syphilis remains a cause of meningitis in Africa. Our data suggest that neuosyphilis remains an important disease in Africa but better prospective studies are needed to understand its epidemiology.
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- 2017
32. Modeling Treatment Strategies to Inform Yaws Eradication.
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Holmes, Alex, Tildesley, Michael J., Solomon, Anthony W., Mabey, David C. W., Sokana, Oliver, Marks, Michael, and Dyson, Louise
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Yaws is a neglected tropical disease targeted for eradication by 2030. To achieve eradication, finding and treating asymptomatic infections as well as clinical cases is crucial. The proposed plan, the Morges strategy, involves rounds of total community treatment (i.e., treating the whole population) and total targeted treatment (TTT) (i.e., treating clinical cases and contacts). However, modeling and empirical work suggests asymptomatic infections often are not found in the same households as clinical cases, reducing the utility of household-based contact tracing for a TTT strategy. We use a model fitted to data from the Solomon Islands to predict the likelihood of elimination of transmission under different intervention schemes and levels of systematic nontreatment resulting from the intervention. Our results indicate that implementing additional treatment rounds through total community treatment is more effective than conducting additional rounds of treatment of at-risk persons through TTT. [ABSTRACT FROM AUTHOR]
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- 2020
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33. Extent and Kinetics of Genetic Change in the omp1 Gene of Chlamydia trachomatis in Two Villages with Endemic Trachoma
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Hayes, Lyn J., Pecharatana, Suphat, Bailey, Robin L., Hampton, Timothy J., Pickett, Mark A., Mabey, David C. W., Watt, Peter J., and Ward, Michael E.
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- 1995
34. Genotyping of Chlamydia trachomatis from a Trachoma-Endemic Village in the Gambia by a Nested Polymerase Chain Reaction: Identification of Strain Variants
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Hayes, Lyn J., Bailey, Robin L., Mabey, David C. W., Clarke, Ian N., Pickett, Mark A., Watt, Peter J., and Ward, Michael E.
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- 1992
35. Conjunctival Scarring in Trachoma Is Associated with Depressed Cell-Mediated Immune Responses to Chlamydial Antigens
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Holland, Martin J., Bailey, Robin L., Hayes, Lyn J., Whittle, Hilton C., and Mabey, David C. W.
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- 1993
36. Short-term increase in prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus following mass drug administration with azithromycin for trachoma control
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Bojang, Ebrima, Jafali, James, Perreten, Vincent, Hart, John, Harding-Esch, Emma M., Sillah, Ansumana, Mabey, David C. W., Holland, Martin J., Bailey, Robin L., Roca, Anna, and Burr, Sarah E.
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Microbiology (medical) ,Trachoma ,630 Agriculture ,lcsh:QR1-502 ,610 Medicine & health ,Azithromycin ,500 Science ,lcsh:Microbiology ,Mass drug administration ,Staphylococcus aureus carriage ,otorhinolaryngologic diseases ,iMLSB ,570 Life sciences ,biology ,Macrolide resistance - Abstract
BACKGROUND Mass drug administration (MDA) with azithromycin is a corner-stone of trachoma control however it may drive the emergence of antimicrobial resistance. In a cluster-randomized trial (Clinical trial gov NCT00792922), we compared the reduction in the prevalence of active trachoma in communities that received three annual rounds of MDA to that in communities that received a single treatment round. We used the framework of this trial to carry out an opportunistic study to investigate if the increased rounds of treatment resulted in increased prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus. Three cross-sectional surveys were conducted in two villages receiving three annual rounds of MDA (3 × treatment arm). Surveys were conducted immediately before the third round of MDA (CSS-1) and at one (CSS-2) and six (CSS-3) months after MDA. The final survey also included six villages that had received only one round of MDA 30 months previously (1 × treatment arm). RESULTS In the 3 × treatment arm, a short-term increase in prevalence of S. aureus carriage was seen following MDA from 24.6% at CSS-1 to 38.6% at CSS-2 (p
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- 2017
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37. Impact of mass drug administration of azithromycin for trachoma elimination on prevalence and azithromycin resistance of genital infection.
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Harrison, Mark Andrew, Harding-Esch, Emma Michele, Marks, Michael, Pond, Marcus James, Butcher, Robert, Solomon, Anthony W., Liqing Zhou, NgeeKeong Tan, Nori, Achyuta V., Kako, Henry, Sokana, Oliver, Mabey, David C. W., Sadiq, Syed Tariq, Zhou, Liqing, and Tan, NgeeKeong
- Abstract
Background: Mass drug administration (MDA) of 20 mg/kg (maximum 1 g in adults) azithromycin for ocular Chlamydia trachomatis (CT) infection is a key component of the WHO trachoma elimination strategy. However, this dose may be suboptimal in Mycoplasma genitalium infection and may encourage emergence of antimicrobial resistance (AMR) to azithromycin.Objectives: To determine the effect of MDA for trachoma elimination on M. genitalium prevalence, strain type and azithromycin resistance.Methods: A secondary analysis of CT-negative vulvovaginal swabs from three outpatient antenatal clinics (Honiara, Solomon Islands) from patients recruited either pre-MDA, or 10 months post-MDA in two cross-sectional surveys was carried out. Swabs were tested for M. genitalium infection using Fast Track Diagnostics Urethritis Plus nucleic acid amplification assay. M. genitalium-positive samples were subsequently tested for azithromycin resistance by sequencing domain V of the 23S rRNA DNA region of M. genitalium and underwent phylogenetic analysis by dual locus sequence typing.Results: M. genitalium prevalence was 11.9% (28/236) in women pre-MDA and 10.9% (28/256) 10 months post-MDA (p=0.7467). Self-reported receipt of azithromycin as part of MDA was 49.2% in women recruited post-MDA and 17.9% (5/28) in those who tested M. genitalium positive. Of samples sequenced (21/28 pre-MDA, 22/28 post-MDA), all showed a macrolide susceptible genotype. Strain typing showed that sequence types diverged into two lineages, with a suggestion of strain replacement post-MDA.Conclusion: A single round of azithromycin MDA in an island population with high baseline M. genitalium prevalence did not appear to impact on either prevalence or azithromycin resistance, in contrast to reported decreased genital CT prevalence in the same population. This may be due to limitations such as sample size, including CT-negative samples only, and low MDA coverage. Further investigation of the impact of multiple rounds of MDA on M. genitalium azithromycin AMR in antibiotic experienced and naïve populations is warranted. [ABSTRACT FROM AUTHOR]- Published
- 2019
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38. Impact of Community Treatment With Ivermectin for the Control of Scabies on the Prevalence of Antibodies to Strongyloides stercoralis in Children.
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Marks, Michael, Gwyn, Sarah, Toloka, Hilary, Kositz, Christian, Asugeni, James, Asugeni, Rowena, Diau, Jason, Kaldor, John M, Romani, Lucia, Redman-MacLaren, Michelle, MacLaren, David, Solomon, Anthony W, Mabey, David C W, Steer, Andrew C, and Martin, Diana
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DRUG administration ,HELMINTHIASIS ,IMMUNOASSAY ,MACROLIDE antibiotics ,PUBLIC health ,RESEARCH ,SCABIES ,TROPICAL medicine ,SEROPREVALENCE ,CHILDREN - Abstract
The prevalence of antibodies to Strongyloides stercoralis was measured in 0–12-year-olds using a bead-based immunoassay before and after ivermectin mass drug administration (MDA) for scabies in the Solomon Islands. Seroprevalence was 9.3% before and 5.1% after MDA (P = .019), demonstrating collateral benefits of ivermectin MDA in this setting. [ABSTRACT FROM AUTHOR]
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- 2020
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39. Correction: Post-Operative Recurrent Trachomatous Trichiasis Is Associated with Increased Conjunctival Expression of S100A7 (Psoriasin)
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Burton, Matthew J., Rajak, Saul N., Ramadhani, Athumani, Weiss, Helen A., Habtamu, Esmael, Abera, Bayeh, Emerson, Paul M., Khaw, Peng T., Mabey, David C. W., Holland, Martin J., and Bailey, Robin L.
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Infectious Diseases ,Arctic medicine. Tropical medicine ,RC955-962 ,Public Health, Environmental and Occupational Health ,Correction ,Public aspects of medicine ,RA1-1270 - Published
- 2013
40. Point-of-care tests for syphilis and yaws in a low-income setting – A qualitative study of healthcare worker and patient experiences.
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Marks, Michael, Esau, Tommy, Asugeni, Rowena, Harrington, Relmah, Diau, Jason, Toloka, Hilary, Asugeni, James, Ansbro, Eimhin, Solomon, Anthony W., Maclaren, David, Redman-Maclaren, Michelle, and Mabey, David C. W.
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SYPHILIS treatment ,YAWS ,MEDICAL care costs ,POINT-of-care testing ,OUTPATIENT medical care ,INFECTIOUS disease transmission - Abstract
Introduction: The human treponematoses comprise venereal syphilis and the three non-venereal or endemic treponematoses yaws, bejel, and pinta. Serological assays remain the most common diagnostic method for all treponemal infections. Point-of-care tests (POCTs) for syphilis and yaws allow testing without further development of infrastructure in populations where routine laboratory facilities are not available. Alongside the test’s performance characteristics assessed through diagnostic evaluation, it is important to consider broader issues when rolling out a POCT. Experience with malaria POCT roll-out in sub-Saharan Africa has demonstrated that both healthcare worker and patient beliefs may play a major role in shaping the real-world use of POCTs. We conducted a qualitative study evaluating healthcare worker and patient perceptions of using a syphilis/yaws POCT in clinics in the East Malaita region of Malaita province in the Solomon Islands. Prior to the study serology was only routinely available at the local district hospital. Methods: The POCT was deployed in the outpatient and ante-natal departments of a district hospital and four rural health clinics served by the hospital. Each site was provided with training and an SOP on the performance, interpretation and recording of results. Treatment for those testing positive was provided, in line with Solomon Islands Ministry of Health and Medical Services’ guidelines for syphilis and yaws respectively. Alongside the implementation of the POCT we facilitated semi-structured interviews with both nurses and patients to explore individuals’ experiences and beliefs in relation to use of the POCT. Results and discussion: Four main themes emerged in the interviews: 1) training and ease of performing the test; 2) time taken and ability to fit the test into a clinical workflow; 3) perceived reliability and trustworthiness of the test; and 4) level of the health care system the test was most usefully deployed. Many healthcare workers related their experience with the POCT to their experience using similar tests for malaria. Although the test was considered to take a relatively long time to perform the benefits of improved access to testing were considered positive by most healthcare workers. Qualitative data is needed to help inform better training packages to support the implementation of POCT in low-resource settings. [ABSTRACT FROM AUTHOR]
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- 2018
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41. Targeted Treatment of Yaws With Household Contact Tracing: How Much Do We Miss?
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Dyson, Louise, Marks, Michael, Crook, Oliver M., Sokana, Oliver, Solomon, Anthony W., Bishop, Alex, Mabey, David C. W., and Hollingsworth, T. Déirdre
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MATHEMATICAL models ,SURVEYS ,THEORY ,AZITHROMYCIN ,YAWS ,DISEASE prevalence ,CONTACT tracing ,INFECTIOUS disease transmission ,THERAPEUTICS - Abstract
Yaws is a disabling bacterial infection found primarily in warm and humid tropical areas. TheWorld Health Organization strategy mandates an initial round of total community treatment (TCT) with single-dose azithromycin followed either by further TCT or active case-finding and treatment of cases and their contacts (the Morges strategy). We sought to investigate the effectiveness of the Morges strategy. We employed a stochastic household model to study the transmission of infection using data collected from a pre-TCT survey conducted in the Solomon Islands. We used thismodel to assess the proportion of asymptomatic infections that occurred in households without active cases. This analysis indicated that targeted treatment of cases and their household contacts wouldmiss a large fraction of asymptomatic infections (65%-100%). This fraction was actually higher at lower prevalences. Even assuming that all active cases and their households were successfully treated, our analysis demonstrated that at all prevalences present in the data set, up to 90% of (active and asymptomatic) infections would not be treated under household-based contact tracing. Mapping was undertaken as part of the study "Epidemiology of Yaws in the Solomon Islands and the Impact of a Trachoma Control Programme," in September-October 2013. contact tracing; household modeling; mass drug administration; modeling; Treponema pallidum pertenue; total community treatment; total targeted treatment; yaws [ABSTRACT FROM AUTHOR]
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- 2018
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42. Direct Whole-Genome Sequencing of Cutaneous Strains of Haemophilus ducreyi.
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Marks, Michael, Fookes, Maria, Wagner, Josef, Ghinai, Rosanna, Sokana, Oliver, Sarkodie, Yaw-Adu, Solomon, Anthony W., Mabey, David C. W., and Thomson, Nicholas R.
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NUCLEOTIDE sequencing ,HAEMOPHILUS diseases ,HAEMOPHILUS ducreyi ,SKIN diseases ,CHANCROID - Abstract
Haemophilus ducreyi, which causes chancroid, has emerged as a cause of pediatric skin disease. Isolation of H. ducreyi in low-income settings is challenging, limiting phylogenetic investigation. Next-generation sequencing demonstrates that cutaneous strains arise from class I and II H. ducreyi clades and that class II may represent a distinct subspecies. [ABSTRACT FROM AUTHOR]
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- 2018
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43. The impact of a single round of community mass treatment with azithromycin on disease severity and ocular Chlamydia trachomatis load in treatment-naïve trachoma-endemic island communities in West Africa.
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Last, Anna R., Burr, Sarah E., Harding-Esch, Emma, Cassama, Eunice, Nabicassa, Meno, Roberts, Chrissy H., Mabey, David C. W., Holland, Martin J., and Bailey, Robin L.
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CHLAMYDIA trachomatis ,SEXUALLY transmitted diseases ,HELMINTHIASIS ,FILARIASIS ,HIV infections ,EPIDEMIOLOGY - Abstract
Background: Trachoma, a neglected tropical disease, is caused by ocular infection with Chlamydia trachomatis (Ct). The World Health Organization (WHO) recommends three annual rounds of community mass drug treatment with azithromycin (MDA) if the prevalence of follicular trachoma in 1-9 year olds (Tf
1-9 ) exceeds 10% at district level to achieve an elimination target of district-level Tf1-9 below 5% after. To evaluate this strategy in treatment-naïve trachomaendemic island communities in Guinea Bissau, we conducted a cross-sectional population-based trachoma survey on four islands. The upper tarsal conjunctivae of each participant were clinically assessed for trachoma and conjunctival swabs were obtained (n = 1507). We used a droplet digital PCR assay to detect Ct infection and estimate bacterial load. We visited the same households during a second cross-sectional survey and repeated the ocular examination and obtained conjunctival swabs from these households one year after MDA (n = 1029). Results: Pre-MDA Tf1-9 was 22.0% (136/618). Overall Ct infection prevalence (CtI) was 18.6% (25.4% in 1-9 year olds). Post-MDA (estimated coverage 70%), Tf1-9 and CtI were significantly reduced (7.4% (29/394, P < 0.001) and 3.3% (34/1029, P < 0.001) (6.6% in 1-9 year olds, P < 0.001), respectively. Median ocular Ct load was reduced from 2038 to 384 copies/swab (P < 0.001). Following MDA cases of Ct infection were highly clustered (Moran's I 0.27, P < 0. 001), with fewer clusters of Ct infection overall, fewer clusters of cases with high load infections and less severe disease. Conclusions: Despite a significant reduction in the number of clusters of Ct infection, mean Ct load, disease severity and presence of clusters of cases of high load Ct infection suggesting the beginning of trachoma control in isolated island communities, following a single round of MDA we demonstrate that transmission is still ongoing. These detailed data are useful in understanding the epidemiology of ocular Ct infection in the context of MDA and the tools employed may have utility in determining trachoma elimination and surveillance activities in similar settings. [ABSTRACT FROM AUTHOR]- Published
- 2017
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44. Immunofibrogenic Gene Expression Patterns in Tanzanian Children with Ocular Chlamydia trachomatis Infection, Active Trachoma and Scarring: Baseline Results of a 4-Year Longitudinal Study.
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Ramadhani, Athumani M., Derrick, Tamsyn, Macleod, David, Massae, Patrick, Mtuy, Tara, Jeffries, David, Roberts, Chrissy H., Bailey, Robin L., Mabey, David C. W., Holland, Martin J., and Burton, Matthew J.
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CHLAMYDIA trachomatis ,GENE expression ,CHILDREN'S health ,BLINDNESS ,PUBLIC health ,THERAPEUTICS - Abstract
Trachoma, caused by Chlamydia trachomatis, is the world's leading infectious cause of blindness and remains a significant public health problem. Much of trachomatous disease pathology is thought to be caused indirectly by host cellular and immune responses, however the immune response during active trachoma and how this initiates progressive scarring is not clearly understood. Defining protective vs. pathogenic immune response to C. trachomatis is important for vaccine design and evaluation. This study reports the baseline results of a longitudinal cohort of Tanzanian children, who were monitored for 4 years in order to determine the immunofibrogenic and infectious correlates of progressive scarring trachoma. In this cohort baseline, 506 children aged 6-10 years were assessed for clinical signs, infection status and the expression of 91 genes of interest prior to mass azithromycin administration for trachoma control. C. trachomatis was detected using droplet digital PCR and gene expression was measured using quantitative real-time PCR. The prevalence of follicles, papillary inflammation and scarring were 33.6, 31.6, and 28.5%, respectively. C. trachomatis was detected in 78/506 (15.4%) individuals, 62/78 of whom also had follicles. C. trachomatis infection was associated with a strong upregulation of IFNG and IL22, the enrichment of Th1 and NK cell pathways and Th17 cell-associated cytokines. In individuals with inflammation in the absence of infection the IFNG/IL22 and NK cell response was reduced, however, pro-inflammatory, growth and matrix factors remained upregulated and mucins were downregulated. Our data suggest that, strong IFNG/IL22 responses, probably related to Th1 and NK cell involvement, is important for clearance of C. trachomatis and that the residual pro-inflammatory and pro-fibrotic phenotype that persists after infection might contribute to pathological scarring. Interestingly, females appear more susceptible to developing papillary inflammation and scarring thanmales, even at this young age, despite comparable levels of C. trachomatis infection. Females also had increased expression of a number of IFNg pathway related genes relative to males, suggesting that overexpression of this pathway in response to infection might contribute to more severe scarring. Longitudinal investigation of these factors will reveal their relative contributions to protection from C. trachomatis infection and development of scarring complications. [ABSTRACT FROM AUTHOR]
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- 2017
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45. Knowledge, attitudes and practices towards yaws and yaws-like skin disease in Ghana.
- Author
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Marks, Michael, Kwakye-Maclean, Cynthia, Doherty, Rachel, Adwere, Paul, Aziz Abdulai, Abdul, Duah, Fredrick, Ohene, Sally-Ann, Mitja, Oriol, Oguti, Blanche, Solomon, Anthony W., Mabey, David C. W., Adu-Sarkodie, Yaw, Asiedu, Kingsley, and Ackumey, Mercy M.
- Subjects
SKIN diseases ,THEMATIC analysis ,YAWS ,PUBLIC health - Abstract
Introduction: Yaws is endemic in Ghana. The World Health Organization (WHO) has launched a new global eradication campaign based on total community mass treatment with azithromycin. Achieving high coverage of mass treatment will be fundamental to the success of this new strategy; coverage is dependent, in part, on appropriate community mobilisation. An understanding of community knowledge, attitudes and practices related to yaws in Ghana and other endemic countries will be vital in designing effective community engagement strategies. Methods: A verbally administered questionnaire was administered to residents in 3 districts in the Eastern region of Ghana where a randomised trial on the treatment of yaws was being conducted. The questionnaire combined both quantitative and qualitative questions covering perceptions of the cause and mechanisms of transmission of yaws-like lesions, the providers from which individuals would seek healthcare for yaws-like lesions, and what factors were important in reaching decisions on where to seek care. Chi-square tests and logistic regression were used to assess relationships between reported knowledge, attitudes and practices, and demographic variables. Thematic analysis of qualitative data was used to identify common themes. Results: A total of 1,162 individuals participated. The majority of individuals (n = 895, 77%) reported that “germs” were the cause of yaws lesions. Overall 13% (n = 161) of respondents believed that the disease was caused by supernatural forces. Participants frequently mentioned lack of personal hygiene, irregular and inefficient bathing, and washing with dirty water as fundamental to both the cause and the prevention of yaws. A majority of individuals reported that they would want to take an antibiotic to prevent the development of yaws if they were asymptomatic (n = 689, 61.2%), but a substantial minority reported they would not want to do so. A majority of individuals (n = 839, 72.7%) reported that if they had a yaws-like skin lesion they would seek care from a doctor or nurse. Both direct and indirect costs of treatment were reported as key factors affecting where participants reported they would seek care. Discussion: This is the first study that has explored community knowledge, attitudes and practices in relation to yaws in any endemic population. The belief that ‘germs’ are in some way related to disease through a variety of transmission routes including both contact and dirty water are similar to those reported for other skin diseases in Ghana. The prominent role of private healthcare providers is an important finding of this study and suggests engagement with this sector will be important in yaws eradication efforts. Strategies to address the substantial minority of individuals who reported they would not take treatment for yaws if they were currently asymptomatic will be needed to ensure the success of yaws eradication efforts. The data collected will be of value to the Ghana Health Service and also to WHO and other partners, who are currently developing community mobilisation tools to support yaws eradication efforts worldwide. [ABSTRACT FROM AUTHOR]
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- 2017
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46. Eyelash Epilation in the Absence of Trichiasis: Results of a Population-Based Prevalence Survey in the Western Division of Fiji.
- Author
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Macleod, Colin, Yalen, Chelsea, Butcher, Robert, Mudaliar, Umesh, Natutusau, Kinisimere, Rainima-Qaniuci, Mere, Haffenden, Chris, Watson, Conall, Cocks, Naomi, Cikamatana, Luisa, Roberts, Chrissy H., Marks, Michael, Rafai, Eric, Mabey, David C. W., Kama, Mike, and Solomon, Anthony W.
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HAIR removal ,EYELASHES ,DISEASE prevalence ,OPHTHALMOLOGY - Abstract
Background: The WHO definition of trachomatous trichiasis (TT) is “at least one eyelash touching the globe, or evidence of recent epilation of in-turned eyelashes”, reflecting the fact that epilation is used as a self-management tool for TT. In Fiji’s Western Division, a high TT prevalence (8.7% in those aged ≥15 years) was reported in a 2012 survey, yet a 2013 survey found no TT and Fijian ophthalmologists rarely see TT cases. Local anecdote suggests that eyelash epilation is a common behaviour, even in the absence of trichiasis. Epilators may have been identified as TT cases in previous surveys. Methods: We used a preliminary focus group to design an interview questionnaire, and subsequently conducted a population-based prevalence survey to estimate the prevalence of epilation in the absence of trichiasis, and factors associated with this behaviour, in the Western Division of Fiji. Results: We sampled 695 individuals aged ≥15 years from a total of 457 households in 23 villages. 125 participants (18%) reported epilating their eyelashes at least once within the past year. Photographs were obtained of the eyes of 121/125 (97%) individuals who epilated, and subsequent analysis by an experienced trachoma grader found no cases of trachomatous conjunctival scarring or trichiasis. The age- and sex- adjusted prevalence of epilation in those aged ≥15 years was 8.6% (95% CI 5.7–11.3%). iTaukei ethnicity, female gender, and a higher frequency of drinking kava root were independently associated with epilation. Conclusion: Epilation occurs in this population in the absence of trichiasis, with sufficient frequency to have markedly inflated previous estimates of local TT prevalence. Individuals with epilated eyelashes should be confirmed as having epilated in-turned eyelashes in an eye with scarring of the conjunctiva before being counted as cases of TT. [ABSTRACT FROM AUTHOR]
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- 2017
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47. Defining Seropositivity Thresholds for Use in Trachoma Elimination Studies.
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Migchelsen, Stephanie J., Martin, Diana L., Southisombath, Khamphoua, Turyaguma, Patrick, Heggen, Anne, Rubangakene, Peter Paul, Joof, Hassan, Makalo, Pateh, Cooley, Gretchen, Gwyn, Sarah, Solomon, Anthony W., Holland, Martin J., Courtright, Paul, Willis, Rebecca, Alexander, Neal D. E., Mabey, David C. W., and Roberts, Chrissy h.
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TRACHOMA ,CHLAMYDIA trachomatis ,SEROPREVALENCE ,DRIED blood spot testing ,RECEIVER operating characteristic curves - Abstract
Background: Efforts are underway to eliminate trachoma as a public health problem by 2020. Programmatic guidelines are based on clinical signs that correlate poorly with Chlamydia trachomatis (Ct) infection in post-treatment and low-endemicity settings. Age-specific seroprevalence of anti Ct Pgp3 antibodies has been proposed as an alternative indicator of the need for intervention. To standardise the use of these tools, it is necessary to develop an analytical approach that performs reproducibly both within and between studies. Methodology: Dried blood spots were collected in 2014 from children aged 1–9 years in Laos (n = 952) and Uganda (n = 2700) and from people aged 1–90 years in The Gambia (n = 1868). Anti-Pgp3 antibodies were detected by ELISA. A number of visual and statistical analytical approaches for defining serological status were compared. Principal Findings: Seroprevalence was estimated at 11.3% (Laos), 13.4% (Uganda) and 29.3% (The Gambia) by visual inspection of the inflection point. The expectation-maximisation algorithm estimated seroprevalence at 10.4% (Laos), 24.3% (Uganda) and 29.3% (The Gambia). Finite mixture model estimates were 15.6% (Laos), 17.1% (Uganda) and 26.2% (The Gambia). Receiver operating characteristic (ROC) curve analysis using a threshold calibrated against external reference specimens estimated the seroprevalence at 6.7% (Laos), 6.8% (Uganda) and 20.9% (The Gambia) when the threshold was set to optimise Youden’s J index. The ROC curve analysis was found to estimate seroprevalence at lower levels than estimates based on thresholds established using internal reference data. Thresholds defined using internal reference threshold methods did not vary substantially between population samples. Conclusions: Internally calibrated approaches to threshold specification are reproducible and consistent and thus have advantages over methods that require external calibrators. We propose that future serological analyses in trachoma use a finite mixture model or expectation-maximisation algorithm as a means of setting the threshold for ELISA data. This will facilitate standardisation and harmonisation between studies and eliminate the need to establish and maintain a global calibration standard. [ABSTRACT FROM AUTHOR]
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- 2017
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48. Mathematical Modeling of Programmatic Requirements for Yaws Eradication.
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Marks, Michael, Mitjà, Oriol, Fitzpatrick, Christopher, Asiedu, Kingsley, Solomon, Anthony W., Mabey, David C. W., and Funk, Sebastian
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YAWS ,TREPONEMATOSES ,ROTATIONAL geometry ,TROPICAL medicine ,SPIROCHAETOSIS ,ANTIBIOTICS ,AZITHROMYCIN ,BACTERIA ,CLIMATOLOGY ,COMPARATIVE studies ,COMPUTER simulation ,RESEARCH methodology ,MEDICAL cooperation ,PROBABILITY theory ,RESEARCH ,RESEARCH funding ,DISEASE relapse ,EVALUATION research ,SYMPTOMS ,STATISTICAL models ,DISEASE eradication ,PREVENTION ,INFECTIOUS disease transmission ,THERAPEUTICS - Abstract
Yaws is targeted for eradication by 2020. The mainstay of the eradication strategy is mass treatment followed by case finding. Modeling has been used to inform programmatic requirements for other neglected tropical diseases and could provide insights into yaws eradication. We developed a model of yaws transmission varying the coverage and number of rounds of treatment. The estimated number of cases arising from an index case (basic reproduction number [R0]) ranged from 1.08 to 3.32. To have 80% probability of achieving eradication, 8 rounds of treatment with 80% coverage were required at low estimates of R0 (1.45). This requirement increased to 95% at high estimates of R0 (2.47). Extending the treatment interval to 12 months increased requirements at all estimates of R0. At high estimates of R0 with 12 monthly rounds of treatment, no combination of variables achieved eradication. Models should be used to guide the scale-up of yaws eradication. [ABSTRACT FROM AUTHOR]
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- 2017
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49. Low Prevalence of Conjunctival Infection with Chlamydia trachomatis in a Treatment-Naïve Trachoma-Endemic Region of the Solomon Islands.
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Butcher, Robert M. R., Sokana, Oliver, Jack, Kelvin, Macleod, Colin K., Marks, Michael E., Kalae, Eric, Sui, Leslie, Russell, Charles, Tutill, Helena J., Williams, Rachel J., Breuer, Judith, Willis, Rebecca, Le Mesurier, Richard T., Mabey, David C. W., Solomon, Anthony W., and Roberts, Chrissy h.
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CONJUNCTIVITIS ,CONJUNCTIVA diseases ,DISEASE prevalence ,CHLAMYDIA trachomatis ,CHLAMYDIA infections ,POLYMERASE chain reaction - Abstract
Background: Trachoma is endemic in several Pacific Island states. Recent surveys across the Solomon Islands indicated that whilst trachomatous inflammation—follicular (TF) was present at levels warranting intervention, the prevalence of trachomatous trichiasis (TT) was low. We set out to determine the relationship between chlamydial infection and trachoma in this population. Methods: We conducted a population-based trachoma prevalence survey of 3674 individuals from two Solomon Islands provinces. Participants were examined for clinical signs of trachoma. Conjunctival swabs were collected from all children aged 1–9 years. We tested swabs for Chlamydia trachomatis (Ct) DNA using droplet digital PCR. Chlamydial DNA from positive swabs was enriched and sequenced for use in phylogenetic analysis. Results: We observed a moderate prevalence of TF in children aged 1–9 years (n = 296/1135, 26.1%) but low prevalence of trachomatous inflammation—intense (TI) (n = 2/1135, 0.2%) and current Ct infection (n = 13/1002, 1.3%) in children aged 1–9 years, and TT in those aged 15+ years (n = 2/2061, 0.1%). Ten of 13 (76.9%) cases of infection were in persons with TF or TI (p = 0.0005). Sequence analysis of the Ct-positive samples yielded 5/13 (38%) complete (>95% coverage of reference) genome sequences, and 8/13 complete plasmid sequences. Complete sequences all aligned most closely to ocular serovar reference strains. Discussion: The low prevalence of TT, TI and Ct infection that we observed are incongruent with the high proportion of children exhibiting signs of TF. TF is present at levels that apparently warrant intervention, but the scarcity of other signs of trachoma indicates the phenotype is mild and may not pose a significant public health threat. Our data suggest that, whilst conjunctival Ct infection appears to be present in the region, it is present at levels that are unlikely to be the dominant driving force for TF in the population. This could be one reason for the low prevalence of TT observed during the study. [ABSTRACT FROM AUTHOR]
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- 2016
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50. Metaanalysis of the Performance of a Combined Treponemal and Nontreponemal Rapid Diagnostic Test for Syphilis and Yaws.
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Marks, Michael, Yin, Yue-Ping, Chen, Xiang-Sheng, Castro, Arnold, Causer, Louise, Guy, Rebecca, Wangnapi, Regina, Mitjà, Oriol, Aziz, Abdul, Castro, Rita, Pereira, Filomena da Luz Martins, Taleo, Fasihah, Guinard, Jérôme, Bélec, Laurent, Tun, Ye, Bottomley, Christian, Ballard, Ronald C., and Mabey, David C. W.
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TREPONEMATOSES ,YAWS ,DIAGNOSIS ,DIAGNOSIS of syphilis ,MEDICAL screening - Abstract
Background. The human treponematoses are important causes of disease. Mother-to-child transmission of syphilis remains a major cause of stillbirth and neonatal death. There are also almost 100 000 cases of endemic treponemal disease reported annually, predominantly yaws. Rapid diagnostic tests (RDTs) would improve access to screening for these diseases. Most RDTs cannot distinguish current and previous infection. The Dual Path Platform (DPP) Syphilis Screen & Confirm test includes both a treponemal (T1) and nontreponemal (T2) component and may improve the accuracy of diagnosis. Methods. We conducted a metaanalysis of published and unpublished evaluations of the DPP-RDT for the diagnosis of syphilis and yaws. We calculated the sensitivity, specificity, and overall agreement of the test compared with reference laboratory tests. Results. Nine evaluations, including 7267 tests, were included. Sensitivity was higher in patients with higher titer rapid plasma reagin (≥1:16) for both the T1 (98.2% vs 90.1%, P< .0001) and the T2 component (98.2% vs 80.6%, P< .0001). Overall agreement between the DPP test and reference serology was 85.2% (84.4%-86.1%). Agreement was highest for high-titer active infection and lowest for past infection. Conclusions. The RDT has good sensitivity and specificity of the treponemal and nontreponemal components both in cases of suspected syphilis and yaws, although the sensitivity is decreased at lower antibody titers. [ABSTRACT FROM AUTHOR]
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- 2016
- Full Text
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