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1. Genome-wide profiling of humoral immunity and pathogen genes under selection identifies immune evasion tactics of Chlamydia trachomatis during ocular infection.

Author

Pickering, Harry, Teng, Andy, Faal, Nkoyo, Joof, Hassan, Makalo, Pateh, Cassama, Eunice, Nabicassa, Meno, Last, Anna R, Burr, Sarah E, Rowland-Jones, Sarah L, Thomson, Nicholas R, Roberts, Chrissy H, Mabey, David CW, Bailey, Robin L, Hayward, Richard D, de la Maza, Luis M, and Holland, Martin J

Subjects
Humans, Chlamydia trachomatis, Trachoma, Antigens, Bacterial, Child, Child, Preschool, Gambia, Guinea-Bissau, Female, Male, Host-Pathogen Interactions, Selection, Genetic, Immunity, Humoral, Immune Evasion, Vaccine Related, Genetics, Infectious Diseases, Clinical Research, Immunization, Prevention, Biotechnology, Human Genome, Sexually Transmitted Infections, Pediatric, 2.1 Biological and endogenous factors, Infection, Inflammatory and Immune System, Antigens, Bacterial, Preschool, Selection, Genetic, Immunity, Humoral, Biochemistry and Cell Biology, Other Physical Sciences
Abstract

The frequency and duration of Chlamydia trachomatis (Ct) ocular infections decrease with age, suggesting development of partial immunity. However, there is a lack of clear correlates of immunity to Ct infection in humans. We screened sera from a cohort of Gambian children followed for six-months against a Ct-proteome microarray. At genome sequence level, we detected signatures of selection from a population of ocular Ct isolates from Guinea-Bissau. Together these approaches allowed us to highlight the focus of humoral responses and hypothesise new modes of pathogen immune evasion. Children who were susceptible to frequent and/or prolonged Ct infection had a less focussed antibody response, including preferential recognition of forty-two antigens. There was evidence of positive and purifying selection across the genome, but little balancing selection. In contrast, most antigens that were associated with susceptibility were under neutral selection. These data suggest an evasion strategy in which Ct presents a large panel of irrelevant antigens to the immune system to block or misdirect protective responses. Development of a focused immune response, possibly induced through vaccination, may be an effective strategy to promote protection to Ct infection.

Published
2017

2. The global burden of trichiasis in 2016.

Author

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

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

BackgroundTrichiasis is present when one or more eyelashes touches the eye. Uncorrected, it can cause blindness. Accurate estimates of numbers affected, and their geographical distribution, help guide resource allocation.MethodsWe obtained district-level trichiasis prevalence estimates in adults for 44 endemic and previously-endemic countries. We used (1) the most recent data for a district, if more than one estimate was available; (2) age- and sex-standardized corrections of historic estimates, where raw data were available; (3) historic estimates adjusted using a mean adjustment factor for districts where raw data were unavailable; and (4) expert assessment of available data for districts for which no prevalence estimates were available.FindingsInternally age- and sex-standardized data represented 1,355 districts and contributed 662 thousand cases (95% confidence interval [CI] 324 thousand-1.1 million) to the global total. Age- and sex-standardized district-level prevalence estimates differed from raw estimates by a mean factor of 0.45 (range 0.03-2.28). Previously non- stratified estimates for 398 districts, adjusted by ×0.45, contributed a further 411 thousand cases (95% CI 283-557 thousand). Eight countries retained previous estimates, contributing 848 thousand cases (95% CI 225 thousand-1.7 million). New expert assessments in 14 countries contributed 862 thousand cases (95% CI 228 thousand-1.7 million). The global trichiasis burden in 2016 was 2.8 million cases (95% CI 1.1-5.2 million).InterpretationThe 2016 estimate is lower than previous estimates, probably due to more and better data; scale-up of trichiasis management services; and reductions in incidence due to lower active trachoma prevalence.

Published
2019
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3. 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

Author

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.

Published
2016
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4. 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

Author

Last, Anna R, Burr, Sarah E, Harding-Esch, Emma, Cassama, Eunice, Nabicassa, Meno, Roberts, Chrissy H, Mabey, David CW, Holland, Martin J, and Bailey, Robin L

Subjects
Trachoma, Community mass treatment, Chlamydia trachomatis, lcsh:RC109-216, Spatial clustering, Bacterial load, Disease severity, lcsh:Infectious and parasitic diseases
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 (TF1–9) 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 trachoma-endemic 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.

Published
2017
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5. PS-003: EVIDENCE-INFORMED POLICY MAKING: CHALLENGES AND OPPORTUNITIES

Author

Makanga, Michael, Beattie, Pauline, Breugelmans, Gabrielle, Nyirenda, Thomas, Bockarie, Moses, Tanner, Marcel, Volmink, Jimmy, Hankins, Catherine, Walzl, Gerhard, Chegou, Novel, Malherbe, Stephanus, Hatherill, Mark, Scriba, Thomas J., Zak, Daniel E., Barry, Clifton E., Kaufmann, Stefan H.E., Noor, Abdisalan, Strub-Wourgaft, Nathalie, Phillips, Patrick, Munguambe, Khátia, Ravinetto, Raffaella, Tinto, Halidou, Diro, Ermias, Mahendrahata, Yodi, Okebe, Joseph, Rijal, Suman, Garcia, Coralith, Sundar, Shyam, Ndayisaba, Gilles, Sopheak, Thai, Ngoduc, Thang, Loen, Harry Van, Jacobs, Jan, D'Alessandro, Umberto, Boelaert, Marleen, Buvé, Anne, Kamalo, Patrick, Manda-Taylor, Lucinda, Rennie, Stuart, Mokgatla, Boitumelo, Bahati, Prince, Ijsselmuiden, Carel, Afolabi, Muhammed, Mcgrath, Nuala, Kampmann, Beate, Imoukhuede, Egeruan, Alexander, Neal, Larson, Heidi, Chandramohan, Daniel, Bojang, Kalifa, Kasaro, Margaret Phiri, Muluka, Brenda, Kaunda, Kaunda, Morse, Jill, Westfall, Andrew, Kapata, Nathan, Kruuner, Annika, Henostroza, German, Reid, Stewart, Alabi, Abraham, Foguim, Francis, Sankarganesh, Jeyaraj, Bruske, Ellen, Mfoumbi, Arnault, Mevyann, Chester, Adegnika, Ayola, Lell, Bertrand, Kranzer, Katharina, Kremsner, Peter, Grobusch, Martin, Sabiiti, Wilber, Ntinginya, Nyanda, Kuchaka, Davis, Azam, Khalide, Kampira, Elizabeth, Mtafya, Bariki, Bowness, Ruth, Bhatt, Nilesh, Davies, Gerry, Kibiki, Gibson, Gillespie, Stephen, Lejon, Veerle, Ilboudo, Hamidou, Mumba, Dieudonné, Camara, Mamady, Kaba, Dramane, Lumbala, Crispin, Fèvre, Eric, Jamonneau, Vincent, Bucheton, Bruno, Büscher, Philippe, Chisenga, Caroline, Sinkala, Edford, Chilengi, Roma, Chitundu, Hellen, Zyambo, Zude, Wandeler, Gilles, Vinikoor, Michael, Emilie, Dama, Camara, Oumou, Mathurin, Koffi, Guiguigbaza-Kossigan, Dayo, Philippe, Büscher, Regassa, Fikru, Hassane, Sakande, Bienvenu, Somda Martin, Fabrice, Courtin, Ouédraogo, Elie, Kouakou, Lingue, Owusu, Michael, Mensah, Eric, Enimil, Anthony, Mutocheluh, Mohamed, Ndongo, Francis Ateba, Tejiokem, Mathurin Cyrille, Texier, Gaetan, Penda, Calixte, Ndiang, Suzie, Ndongo, Jean-Audrey, Guemkam, Georgette, Sofeu, Casimir Ledoux, Afumbom, Kfutwa, Faye, Albert, Msellati, Philippe, Warszawski, Josiane, Vos, Alinda, Devillé, Walter, Barth, Roos, Klipstein-Grobusch, Kerstin, Tempelman, Hugo, Venter, François, Coutinho, Roel, Grobbee, Diederick, Ssemwanga, Deogratius, Lyagoba, Frederick, Magambo, Brian, Kapaata, Anne, Kirangwa, Joseph, Nannyonjo, Maria, Nassolo, Faridah, Nsubuga, Rebecca, Yebra, Gonzalo, Brown, Andrew, Kaleebu, Pontiano, Nylén, Hanna, Habtewold, Abiy, Makonnen, Eyasu, Yimer, Getnet, Burhenne, Jürgen, Diczfalusy, Ulf, Aklillu, Eleni, Steele, Duncan, Walker, Richard, Simuyandi, Michelo, Beres, Laura, Bosomprah, Samuel, Ansumana, Rashid, Taitt, C., Lamin, J.M., Jacobsen, K.H., Mulvaney, S.P., Leski, T., Bangura, U., Stenger, D., Vries, Sophie De, Zinsou, Frejus Jeannot, Honkpehedji, J, Dejon, Jean Claude, Loembe, Marguerite Massinga, Bache, Bache, Pakker, Nadine, Leeuwen, Remko Van, Hounkpatin, Aurore Bouyoukou, Yazdanbakhsh, Maria, Bethony, Jeffrey, Hotez, Peter, Diemert, David, Bache, Bache Emmanuel, Fernandes, José F., Mba, Régis M Obiang, Kabwende, Anita L., Grobusch, Martin P., Krishna, Sanjeev, Kremsner, Peter G., Todagbe, Agnandji Selidji, Nambozi, Michael, Kabuya, Jean-Bertin, Hachizovu, Sebastian, Mwakazanga, David, Kasongo, Webster, Buyze, Jozefien, Mulenga, Modest, Geertruyden, Jean-Pierre, Gitaka, Jesse, Chan, Chim, Kongere, James, Kagaya, Wataru, Kaneko, Akira, Kabore, Naomie, Barry, Nouhoun, Kabre, Zachari, Werme, Karidia, Fofana, Aminata, Compaore, Daniel, Nikiema, Frederic, Some, Fabrice, Djimde, Abdoulaye, Zongo, Issaka, Ouedraogo, Bosco, Kone, Aminatou, Sagara, Issaka, Björkman, Anders, Gil, Jose Pedro, Nchinda, Godwin, Bopda, Alain, Nji, Nadesh, Ambada, Georgia, Ngu, Loveline, Tchadji, Jules, Sake, Carol, Magagoum, Suzanne, Njambe, Ghislain D., Lisom, Abel, Park, Chae Gyu, Tait, Dereck, Sibusiso, Hlatjwako, Manda, Olga, Croucher, Kristin, Westhuizen, Anja Van Der, Mshanga, Isaac, Levin, Jonathan, Nanvubya, Annet, Kibengo, Freddie, Jaoko, Walter, Pala, Pietro, Perreau, Matthieu, Namuniina, Annemarie, Kitandwe, Paul, Tapia, Gonzalo, Serwanga, Jennifer, Yates, Nicole, Fast, Pat, Mayer, Bryan, Montefiori, David, Tomaras, Georgia, Robb, Merlin, Lee, Carter, Wagner, Ralf, Sanders, Edward, Kilembe, William, Kiwanuka, Noah, Gilmour, Jill, Kuipers, Hester, Vooij, Dani, Chinyenze, Kundai, Priddy, Frances, Ding, Song, Hanke, Tom, Pantaleo, Giuseppe, Ngasala, Billy, Jovel, Irina, Malmberg, Maja, Mmbando, Bruno, Premji, Zul, Mårtensson, Andreas, Mwaiswelo, Richard, Agbor, Lenshina, Apinjoh, Tobias, Mwanza, Sydney, Chileshe, Justin, Joshi, Sudhaunshu, Malunga, Phidelis, Manyando, Christine, Laufer, Miriam, Dara, Antoine, Niangaly, Amadou, Sinha, Indranil, Brodin, David, Fofana, Bakary, Dama, Souleymane, Dembele, Demba, Sidibe, Bakary, Diallo, Nouhoum, Thera, Mahamadou, Wright, Karin, Gil, Jose, Doumbo, Ogobara, Baraka, Vito, Nabasumba, Carolyn, Francis, Filbert, Lutumba, Pascal, Mavoko, Hypolite, Alifrangis, Michael, Geertruyden, Jean-Pierre Van, Sissoko, Sekou, Sangaré, Cheick, Toure, Sekou, Sanogo, Kassim, Diakite, Hamadoun, Toure, Siaka, Doumbia, Diagassan, Haidara, Kadiatou, Julé, Amélie, Ashurst, Hazel, Merson, Laura, Olliaro, Piero, Marsh, Vicki, Lang, Trudie, Guérin, Philippe, Awuondo, Kennedy, Njenga, Daniel, Nyakarungu, Elizabeth, Titus, Pauline, Sutamihardja, Awalludin, Lowe, Brett, Ogutu, Bernhards, Billingsley, Peter, Soulama, Issiaka, Kaboré, Moïse, Coulibaly, Aboubacar, Ouattara, Maurice, Sanon, Souleymane, Diarra, Amidou, Bougouma, Edith, Ouedraogo, Alphonse, Sombie, Benjamin, Ouedraogo, Amidou, Kargougou, Désiré, Ouattara, Daouda, Issa, Nebie, Tiono, Alfred, Sirima, Sodiomon, Chaponda, Mike, Dabira, Edgard, Dao, François, Dara, Nianwalou, Sidibe, Bouran, Coulibaly, Moctar, Tolo, Allaye, Maiga, Hamma, Ouologuem, Nouhoum, Niangaly, Hamidou, Botchway, Felix, Wilson, Nana, Dickinson-Copeland, Carmen M, Adjei, Andrew A., Wilson, Michael, Stiles, Jonathan K., Hamid, Muzamil Abdel, Awad-Elgeid, Mona, Nasr, Awad, Netongo, Palmer, Kamdem, Séverin, Velavan, Thirumalaisamy, Lasry, Estrella, Diarra, Modibo, Bamadio, Amadou, Traore, Aliou, Coumare, Samba, Soma, Bahonan, Dicko, Yeyia, Sangare, Boubou, Tembely, Aly, Traore, Djibril, Haidara, Aboubecrin, Dicko, Alassane, Diawara, Elisabeth, Beavogui, Abdoul, Camara, Daouda, Sylla, Malick, Yattara, Mohamed, Sow, Amadou, Camara, Gnèpou Camara, Diallo, Saliou, Mombo-Ngoma, Ghyslain, Remppis, Jonathan, Sievers, Moritz, Manego, Rella Zoleko, Endamne, Lilian, Hutchinson, David, Held, Jana, Supan, Christian, Salazar, Carmen L. Ospina, Bonkian, Léa Nadège, Nahum, Alain, Sié, Ali, Abdulla, Salim, Cantalloube, Cathy, Djeriou, Elhadj, Bouyou-Akotet, Marielle, Mordmüller, Benjamin, Siribie, Mohamadou, Sirima, Sodiomon B., Ouattara, San Maurice, Coulibaly, Sam, Kabore, Jean Moïse, Amidou, Diarra, Tekete, Mamadou, Burhenne, Juergen, Traore, Oumar, Haefeli, Walter, Borrmann, Steffen, Kaboré, Naomie, Kabré, Zachari, Nikèma, Fréderic, Compaoré, Daniel, Somé, Fabrice, Djimdé, Abdoulaye, Ouédraogo, Jean, Chalwe, Victor, Miller, John, Diakité, Hamadoun, Greco, Beatrice, Spangenberg, Thomas, Kourany-Lefoll, Elly, Oeuvray, Claude, Mulry, Jim, Tyagarajan, Kamala, Magsaam, Bettina, Barnes, Karen, Hodel, Eva Maria, Humphreys, Georgina, Pace, Cheryl, Banda, C.G, Denti, Paulo, Allen, Elizabeth, Lalloo, David, Mwapasa, Victor, Terlouw, Anja, Mwesigwa, Julia, Achan, Jane, Jawara, Musa, Ditanna, Gian, Worwui, Archibald, Affara, Muna, Koukouikila-Koussounda, Félix, Kombo, Michael, Vouvoungui, Christevy, Ntoumi, Francine, Etoka-Beka, Mandingha Kosso, Deibert, Julia, Poulain, Pierre, Kobawila, Simon, Gueye, Nerly Gampio, Koukouikila-Koussounda, Felix, Seda, Brian, Kwambai, Titus, Jangu, Phelix, Samuels, Aaron, ter Kuile, Feike, Kariuki, Simon, Barry, Aissata, Bousema, Teun, Okech, Brenda, Egwang, Thomas, Corran, Patrick, Riley, Eleanor, Ezennia, Ifeoma, Ekwunife, Obinna, Muleba, Mbanga, Stevenson, Jennifer, Mbata, Keith, Coetzee, Maureen, Norris, Douglas, Moneke-Anyanwoke, Ngozi, Momodou, Jasseh, Clarke, Ed, Scott, Susana, Tijani, Adelani, Djimde, Moussa, Vaillant, Michel, Samouda, Hanen, Mensah, Victorine, Roetynck, Sophie, Kanteh, Ebrima, Bowyer, Georgina, Ndaw, Amy, Oko, Francis, Bliss, Carly, Jagne, Ya Jankey, Cortese, Riccardo, Nicosia, Alfredo, Roberts, Rachel, D'Alessio, Flavia, Leroy, Odile, Faye, Babacar, Cisse, Badara, Gerry, Stephen, Viebig, Nicola, Lawrie, Alison, Ewer, Katie, Hill, Adrian, Nebie, Issa, Tiono, Alfred B, Sanou, Guillaume, Konate, Amadou T, Yaro, Baptiste J, Sodiomon, Sirima, Honkpehedji, Yabo, Agobe, Jean Claude Dejon, Zinsou, Frejus, Mengue, Juliana, Richie, Thomas, Hoffman, Stephen, Nouatin, Odilon, Ngoa, Ulysse Ateba, Edoa, Jean R, Homoet, Andreas, Engelhon, Julie Englhon, Massinga-Louembe, Marguerite, Esen, Meral, Theisen, Michael, Sim, Kim Lee, Luty, Adrian Jf, Moutairou, Kabirou, Dinko, Bismarck, King, Elizabeth, Targett, Geoffrey, Sutherland, Colin, Likhovole, Clement, Ouma, Collins, Vulule, John, Musau, Susan, Khayumbi, Jeremiah, Okumu, Albert, Murithi, Wilfred, Otu, Jacob, Gehre, Florian, Zingue, Dezemon, Kudzawu, Samuel, Forson, Audrey, Mane, Morto, Rabna, Paulo, Diarra, Bassirou, Kayede, Salako, Adebiyi, Emmanuel, Kehinde, Aderemi, Onyejepu, Nneka, Onubogu, Catherine, Idigbe, Emmanuel, Ba, Awa, Diallo, Aissatou, Mboup, Souleymane, Disse, Kodjo, Kadanga, Gerard, Dagnra, Yaotse, Baldeh, Ignatius, Corrah, Tumani, Jong, Bouke De, Antonio, Martin, Musanabaganwa, Clarisse, Musabyimana, Jean Pierre, Karita, Etienne, Diop, Blondin, Nambajimana, Abidan, Dushimiyimana, Valentine, Karame, Prosper, Russell, Jim, Ndoli, Jules, Hategekimana, Theobald, Sendegeya, Augustin, Condo, Jeannine, Binagwaho, Agnes, Okonko, Iheanyi, Okerentugba, Phillip, Opaleye, Oluyinka, Awujo, Ezinwanne, Frank-Peterside, Nnenna, Moyo, Sikhulile, Kotokwe, Kenanao, Mohammed, Terence, Boleo, Coretah, Mupfumi, Lucy, Chishala, Samuel, Gaseitsiwe, Simani, Tsalaile, Lesedi, Bussmann, Herman, Makhema, Joseph, Baum, Marianna, Marlink, Richard, Engelbretch, Susan, Essex, Max, Novitsky, Vladimir, Saka, Emmanuel, Kalipalire, Zex, Bhairavabhotla, Ravikiran, Midiani, Dalitso, Sherman, Judith, Mgode, Georgies, Cox, Christophe, Bwana, Dickens, Mtui, Leah, Magesa, Daniel, Kahwa, Amos, Mfinanga, Godfrey, Mulder, Christiaan, Borain, Nick, Petersen, Lizette, Plessis, Julianne Du, Theron, Grant, Holm-Hansen, Carol, Tekwu, Emmanuel Mouafo, Sidze, Larissa Kamgue, Assam, Jean Paul Assam, Eyangoh, Sarah, Niemann, Stefan, Beng, Veronique Penlap, Frank, Matthias, Atiadeve, Samuel, Hilmann, Doris, Awoniyi, Dolapo, Baumann, Ralf, Kriel, Belinda, Jacobs, Ruschca, Kidd, Martin, Loxton, Andre, Kaempfer, Susanne, Singh, Mahavir, Mwanza, Winnie, Milimo, Deborah, Moyo, Maureen, Kasese, Nkatya, Cheeba-Lengwe, Maina, Munkondya, Stembiso, Ayles, Helen, Haas, Petra De, Muyoyeta, Monde, Namuganga, Anna Ritah, Kizza, Harriet Mayanja, Mendy, Alieu, Tientcheu, Leopold, Ayorinde, Abigail, Coker, Edward, Egere, Uzochukwu, Coussens, Anna, Naude, Celeste, Chaplin, George, Noursadeghi, Mahdad, Martineau, Adrian, Jablonski, Nina, Wilkinson, Robert, Ouedraogo, Henri Gautier, Matteelli, Alberto, Regazzi, Mario, Tarnagda, Grissoum, Villani, Paola, Sulis, Giorgia, Diagbouga, Serge, Roggi, Alberto, Giorgetti, Francesco, Kouanda, Seni, Bidias, Amel, Ndjonka, Dieudonné, Olemba, Clémence, Souleymanou, Arabo, Mukonzo, Jackson, Kuteesa, Ronald, Ogwal-Okeng, Jasper, Gustafsson, Lars L., Owen, Joel, Bassi, Peter, Gashau, Wadzani, Olaf, Klungel, Dodoo, Alexander, Okonkwo, Prosper, Kanki, Phyllis, Maruapula, Dorcas, Seraise, Boitumelo, Einkauf, Kevin, Reilly, Amanda, Rowley, Christopher, Musonda, Rosemary, Framhein, Anna, Mpagama, Stella, Semvua, Hadija, Maboko, Leonard, Hoelscher, Michael, Heinrich, Norbert, Mulenga, Lloyd, Kaayunga, Callistus, Davies, Mary-Ann, Egger, Matthias, Musukuma, Kalo, Dambe, Rosalia, Usadi, Benjamin, Ngari, Moses, Thitiri, Johnstone, Mwalekwa, Laura, Fegan, Greg, Berkley, James, Nsagha, Dickson, Munamunungu, Virginia, Bolton, Carolyn, Siyunda, Alice, Shilimi, Jacinta, Bucciardini, Raffaella, Fragola, Vincenzo, Abegaz, Teshome, Lucattini, Stefano, Halifom, Atakilt, Tadesse, Eskedar, Berhe, Micheal, Pugliese, Katherina, Castro, Paola De, Terlizzi, Roberta, Fucili, Luca, Gregorio, Massimiliano Di, Mirra, Marco, Zegeye, Teame, Binelli, Andrea, Vella, Stefano, Abraham, Loko, Godefay, Hagos, Rakotoarivelo, Rivo, Raberahona, Mihaja, Randriamampionona, Njary, Andriamihaja, Rabezanahary, Rasamoelina, Tahinamandranto, Cornet, Muriel, Randria, Mamy Jean De Dieu, Benet, Thomas, Vanhems, Philippe, Andrianarivelo, Mala Rakoto, Chirwa, Uchizi, Michelo, Charles, Hamoonga, Raymond, Wandiga, Steve, Oduor, Patience, Agaya, Janet, Sharma, Aditya, Cavanaugh, Sean, Cain, Kevin, Mukisa, John, Mupere, Ezekiel, Worodria, William, Ngom, Justice Trésor, Koro, Francioli, Godwe, Celestin, Adande, Clemence, Ateugieu, Romaric, Onana, Tatiana, Ngono, Annie, Kamdem, Yannick, Ngo-Niobe, Sara, Etoa, François-Xavier, Kanengoni, Muchineripi, Ruzario, Sithembile, Ndebele, Paul, Shana, Melody, Tarumbiswa, Fadzai, Musesengwa, Rosemary, Gutsire, Rutendo, Fisher, Kevin, Thyagarajan, Bargavi, Akanbi, Olusola, Binuyo, Michael, Ssengooba, Willy, Respeito, Durval, Mambuque, Edson, Blanco, Silvia, Mandomando, Inacio, Cobelens, Frank, Garcia-Basteiro, Alberto, Tamene, Ayele, Topp, Stephanie, Mwamba, Chanda, Padian, Nancy, Sikazwe, Izukanji, Geng, Elvin, Holmes, Charles, Sikombe, Kombatende, Hantuba, Cardinal, Czaicki, Nancy, Simbeza, Sandra, Somwe, Paul, Umulisa, Michele, Ilo, Jennifer, Kestelyn, Evelyne, Uwineza, Mireille, Agaba, Stephen, Delvaux, Therese, Wijgert, Janneke, Gethi, Dickson, Odeny, Lazarus, Tamandjou, Cynthia, Kaindjee-Tjituka, Francina, Brandt, Laura, Cotton, Mark, Nel, Etienne, Preiser, Wolfgang, Andersson, Monique, Adepoju, Abiola, Magana, Musa, Etsetowaghan, Andrew, Chilikwazi, Mutinta, Sutcliffe, Catherine, Thuma, Philip, Sinywimaanzi, Kathy, Matakala, Hellen, Munachoonga, Passwell, Moss, William, Masenza, Issa Sabi, Geisenberger, Otto, Agrea, Peter, Rwegoshora, France, Mahiga, Hellen, Olomi, Willyhelmina, Kroidl, Arne, Kayode, Gbenga, Amoakoh-Coleman, Mary, Ansah, Evelyn, Uthman, Olalekan, Fokam, Joseph, Santoro, Maria-Mercedes, Musolo, Chrissie, Chimbiri, Isabel, Chikwenga, Gloria, Deula, Ruth, Massari, Riccardo, Lungu, Agness, Perno, Carlo-Federico, Ndzengue, Georgia, Loveline, Ngu, Lissom, Abel, Flaurent, Tchouangueu, Sosso, Samuel, Essomba, Claudine, Kpeli, Grace, Otchere, Isaac, Lamelas, Araceli, Buultjens, Andrew, Bulach, Dieter, Baines, Sarah, Seemann, Torsten, Giulieri, Stefano, Nakobu, Zuliehatu, Aboagye, Samuel, Owusu-Mireku, Evelyn, Danso, Emelia, Hauser, Julia, Hinic, Vladimira, Pluschke, Gerd, Stinear, Timothy, Yeboah-Manu, Dorothy, Elshayeb, Ayman, Siddig, Marmar El, Ahmed, Abdel Azim, Hussien, Adil El, Kabwe, Mwila, Tembo, John, Chilukutu, Lophina, Chilufya, Moses, Ngulube, Francis, Lukwesa, Chileshe, Enne, Virve, Wexner, Hannah, Mwananyanda, Lawrence, Hamer, Davidson, Sinyangwe, Sylvester, Ahmed, Yusuf, Klein, Nigel, Maeurer, Markus, Zumla, Ali, Bates, Matthew, Beyala, Landry, Etienne, Guenou, Anthony, Njimbia, Benjamin, Azike, Ateudjieu, Jerome, Chibwe, Bertha, Ojok, David, Tarr, Christine Attia, Perez, Guillermo Martinez, Omeonga, Senga, Kibungu, Fanta, Meyer, Ana, Lansana, Peter, Mayor, Alfredo, Onyango, Peter, Loggerenberg, François Van, Furtado, Tamzin, Boggs, Liam, Segrt, Alexis, Dochez, Carine, Burnett, Rosemary, Mphahlele, M. Jeffrey, Miiro, George, Mbidde, Edward, Peshu, Norbert, Kivaya, Esther, Ngowi, Bernard, Kavishe, Reginald, Maowia, Mukhtar, Sandstrom, Eric, Ayuo, Elizabeth, Mmbaga, Blandina, Leisegang, Cordelia, Thorpe, Marie, Batchilly, Elizabeth, N'Guessan, Jean-Pierre, Kanteh, Dembo, Søfteland, Solrun, Sebitloane, Motshedisi, Vwalika, Bellington, Taylor, Myra, Galappaththi-Arachchige, Hashini, Holmen, Sigve, Gundersen, Svein Gunnar, Ndhlovu, Patricia, Kjetland, Eyrun Floerecke, Kombe, Francis, Toohey, Jacintha, Pienaar, Elizabeth, Kredo, Tamara, Cham, Pa Modou, Abubakar, Ismaela, Dondeh, Bai Lamin, Vischer, Nerina, Pfeiffer, Constanze, Burri, Christian, Musukwa, Kalo, Zürcher, Samuel, Mwandu, Temwani, Bauer, Sophie, Adriko, Moses, Mwaura, Peter, Omolloh, Kevin, Jones, Clarer, Malecela, Mwelecele, Hamidu, Buhari Adamu, Jenner, Tettevi Edward, Asiedu, Larbi John, Osei-Atweneboana, Mike, Afeke, Innocent, Addo, Phyllis, Newman, Mercy, Durnez, Lies, Eddyani, Miriam, Ammisah, Nana, Abas, Mona, Quartey, Maxwell, Ablordey, Anthony, Akinwale, Olaoluwa, Adeneye, Adeniyi, Ezeugwu, Sylvanus, Olukosi, Yetunde, Adewale, Babatunde, Sulyman, Medinat, Mafe, Margaret, Okwuzu, Jane, Gyang, Pam, Nwafor, Timothy, Henry, Uzoma, Musa, Bilkisu, Ujah, Innocent, Agobé, Jean Claude Dejon, Grau-Pujol, Berta, Sacoor, Charfudin, Nhabomba, Augusto, Casellas, Aina, Quintó, Llorenç, Subirà, Carme, Giné, Ricard, Valentín, Antònia, Muñoz, Jose, Nikiema, Marguerite, Ky-Ba, Absatou, Comapore, Kiswendsida Abdou Muller, Traore, Alfred, Sangare, Lassana, Oluremi, Adeolu, Michel, Mandro, Camara, Yaya, Sanneh, Bakary, Cuamba, Inocencia, Gutiérrez, Jose, Lázaro, Carlota, Mejia, Rojelio, Adedeji, Abimbola, Folorunsho, Sola, Demehin, Pelumi, Akinsanya, Bamidele, Cowley, Giovanna, Silva, Eunice Teixeira Da, Nabicassa, Meno, Barros, Pedrozinho Duarte Pereira De, Blif, Milena Mbote, Bailey, Robin, Last, Anna, Mahendradhata, Yodi, Gotuzzo, Eduardo, Nys, Kateljine De, Casteels, Minnes, Nona, Sylvie Kwedi, Lumeka, Kabwende, Todagbe, Agnandji, Djima, Mariam Mama, Ukpong, Morenike, Sagay, Atiene, Khamofu, Hadiza, Torpey, Kwasi, Afiadigwe, Evaristus, Anenih, James, Ezechi, Oliver, Nweneka, Chidi, Idoko, John, Muhumuza, Simon, Katahoire, Anne, Nuwaha, Fred, Olsen, Annette, Okeyo, Seth, Omollo, Raymond, Kimutai, Robert, Ochieng, Michael, Egondi, Thaddaeus, Moonga, Clement, Chileshe, Chisele, Magwende, George, Anumudu, Chiaka, Onile, Olugbenga, Oladele, Victoria, Adebayo, Adewale, Awobode, Henrietta, Oyeyemi, Oyetunde, Odaibo, Alexander, Kabuye, Emily, Lutalo, Tom, Njua-Yafi, Clarisse, Nkuo-Akenji, Theresa, Anchang-Kimbi, Judith, Mugri, Regina, Chi, Hanesh, Tata, Rolland, Njumkeng, Charles, Dodoo, Daniel, Achidi, Eric, Fernandes, José, Bache, Emmanuel B., Matakala, Kalumbu, Searle, Kelly, Greenman, Michelle, and Rainwater-Lovett, Kaitlin

Subjects
Abstracts of Poster Presentations, Abstracts of Oral Presentations, Author Index, Abstracts of Presentations in Plenary Sessions, Article, Abstracts of the Eighth Edctp Forum, 6–9 November 2016
Published
2017

6. The global burden of trichiasis in 2016

Author

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

Subjects
Geography, Trachoma, Blindness, Incidence (epidemiology), medicine, Age and sex, Raw data, medicine.disease, Trichiasis, Confidence interval, Demography, District level
Abstract

BackgroundTrichiasis is present when one or more eyelashes touches the eye. Uncorrected, it can cause blindness. Accurate estimates of numbers affected, and their geographical distribution, help guide resource allocation.MethodsWe obtained district-level trichiasis prevalence estimates for 44 endemic and previously-endemic countries. We used (1) the most recent data for a district, if more than one estimate was available; (2) age- and sex-standardized corrections of historic estimates, where raw data were available; (3) historic estimates adjusted using a mean adjustment factor for districts where raw data were unavailable; and (4) expert assessment of available data for districts for which no prevalence estimates were available.FindingsInternally age- and sex-standardized data represented 1,355 districts and contributed 662 thousand cases (95% confidence interval [CI] 324 thousand-1.1 million) to the global total. age- and sex-standardized district-level prevalence estimates differed from raw estimates by a mean factor of 0.45 (range 0.03-2.28). Previously non-standardized estimates for 398 districts, adjusted by ×0.45, contributed a further 411 thousand cases (95% CI 283-557 thousand). Eight countries retained previous estimates, contributing 848 thousand cases (95% CI 225 thousand-1.7 million). New expert assessments in 14 countries contributed 862 thousand cases (95% CI 228 thousand-1.7 million). The global trichiasis burden in 2016 was 2.8 million cases (95% CI 1.1-5.2 million).InterpretationThe 2016 estimate is lower than previous estimates, probably due to more and better data; scale-up of trichiasis management services; and reductions in incidence due to lower active trachoma prevalence.Author SummaryAs an individual with trichiasis blinks, the eyelashes abrade the cornea, which can lead to corneal opacity and blindness. Through high quality surgery, which involves correcting the position of the in-turned eyelid, it is possible to reduce the number of people with trichiasis. An accurate estimate of the number of persons with trichiasis and their geographical distribution are needed in order to effectively align resources for surgery and other necessary services. We obtained district-level trichiasis prevalence estimates for 44 endemic and previously-endemic countries. We used the most recently available data and expert assessments to estimate the global burden of trichiasis. We estimated that in 2016 the global burden was 2.8 million cases (95% CI 1.1-5.2 million).The 2016 estimate is lower than previous estimates, probably due to more and better data; scale-up of trichiasis management services; and reductions in incidence due to lower active trachoma prevalence.

Published
2018
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7. Plasmid Copy Number and Disease Severity in Naturally Occurring Ocular Chlamydia trachomatis Infection

Author

Last, Anna R, Roberts, Chrissy H, Cassama, Eunice, Nabicassa, Meno, Molina-Gonzalez, Sandra, Burr, Sarah E, Mabey, David CW, Bailey, Robin L, and Holland, Martin J

Subjects
Adult, Aged, 80 and over, Male, Trachoma, Adolescent, Virulence, Chlamydiology and Rickettsiology, Gene Dosage, Infant, Chlamydia trachomatis, Middle Aged, Severity of Illness Index, Bacterial Load, Young Adult, Child, Preschool, Humans, Female, Child, Aged, Plasmids
Abstract

The Chlamydia trachomatis plasmid is a virulence factor. Plasmid copy number, C. trachomatis load and disease severity were assessed in a treatment-naive population where trachoma is hyperendemic. By using droplet digital PCR, plasmid copy number was found to be stable (median, 5.34 [range, 1 to 18]) and there were no associations with C. trachomatis load or disease severity.

Published
2014

8. Can corneal pannus with trachomatous inflammation--follicular be used in combination as an improved specific clinical sign for current ocular Chlamydia trachomatis infection?

Author

Derrick, Tamsyn, Holland, Martin J, Cassama, Eunice, Markham-David, Rod, Nabicassa, Meno, Marks, Michael, Bailey, Robin L, and Last, Anna R

Subjects
sense organs, eye diseases
Abstract

BACKGROUND: Trachoma is a blinding disease caused by conjunctival infection with Chlamydia trachomatis (Ct). Mass drug administration (MDA) for trachoma control is administered based on the population prevalence of the clinical sign of trachomatis inflammation - follicular (TF). However, the prevalence of TF is often much higher than the prevalence of Ct infection. The addition of a clinical sign specific for current ocular Ct infection to TF could save resources by preventing unnecessary additional rounds of MDA. METHODS: Study participants were aged between 1-9 years and resided on 7 islands of the Bijagos Archipelago, Guinea Bissau. Clinical grades for trachoma and corneal pannus and ocular swab samples were taken from 80 children with TF and from 81 matched controls without clinical evidence of trachoma. Ct infection testing was performed using droplet digital PCR. RESULTS: New pannus was significantly associated with Ct infection after adjustment for TF (P = 0.009, OR = 3.65 (1.4-9.8)). Amongst individuals with TF, individuals with new pannus had significantly more Ct infection than individuals with none or old pannus (75.0% vs 45.5%, Chi(2) P = 0.01). TF and new pannus together provide a highly specific (91.7%), but a poorly sensitive (51.9%) clinical diagnostic test for Ct infection. CONCLUSIONS: As we move towards trachoma elimination it may be desirable to use a combined clinical sign (new pannus in addition to TF) that is highly specific for current ocular Ct infection. This would allow national health systems to obtain a more accurate estimate of Ct population prevalence to inform further need for MDA without the expense of Ct molecular diagnostics, which are currently unaffordable in programmatic contexts.

Published
2016

9. Additional file 7: of Inverse relationship between microRNA-155 and -184 expression with increasing conjunctival inflammation during ocular Chlamydia trachomatis infection

Author

Tamsyn Derrick, Last, Anna, Burr, Sarah, Roberts, Chrissy, Nabicassa, Meno, Cassama, Eunice, Bailey, Robin, Mabey, David, Burton, Matthew, and Holland, Martin

Abstract

Multivariable regression model of the contribution of miR expression to clinical papillary hypertrophy score. Collapsed papillary hypertrophy score (P0, P1 or P2/3, as defined by the WHO 1981 FPC scoring system) was used as an ordinal outcome variable to define trachomatous inflammation in 163 clinical samples. Age, gender, Ct load and inverted ∆CT values (40-∆CT) of miR are included as independent variables. Model AIC (Akaike information criterion) is 227.3725. aOR = Odds ratio, bCI = confidence intervals, cCt load is defined as log-(e) omcB copies/swab. (PDF 59 kb)

Published
2016
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11. Health Beliefs and Perceptions of Trachoma in Communities on the Bijagos Archipelago of Guinea Bissau

Author

Thompson, Katie, Hutchins, Harry, Baio, Aramata, Cassama, Eunice, Nabicassa, Meno, Bailey, Robin, and Last, Anna R.

Subjects
Adult, Male, Rural Population, Trachoma, Health Knowledge, Attitudes, Practice, Trichiasis, interviews, Adolescent, Health Behavior, Original Articles, Middle Aged, Health Services Accessibility, hygiene, Young Adult, health beliefs, qualitative, Humans, Bijagos, Guinea-Bissau, Female, Attitude to Health
Abstract

Purpose: The World Health Organization aims to eliminate blinding trachoma by 2020 using the SAFE strategy: Surgery for trichiasis, Antibiotics, Facial cleanliness and Environmental improvement. Trachoma is hyperendemic on the remote Bijagos Archipelago of Guinea-Bissau, West Africa. Sociocultural factors remain unexplored here, despite their potential impact on disease control, particularly through the “F” and “E” aspects. By examining these, we aim to illuminate this population's unreported health beliefs, hygiene behaviors and disease perceptions. This understanding will help to optimize future public health interventions, and guide the distribution of limited healthcare resources. Methods: Two unmatched interview series were conducted 1 year apart on Bubaque Island in the Bijagos Archipelago; one in rural villages using purposive snowball sampling, the other in a semi-urban settlement, using random-cluster sampling. Interviews were conducted and recorded in Kriolu, the local dialect, by a supervised local field assistant before translation into English for conventional content analysis. Results: Trachoma was unheard of in either series, despite ongoing local trachoma research. A heterogeneous range of disease etiology and preventative measures were suggested, but the importance of hygiene was more widely reported by semi-urban interviewees. Although western medicine was well regarded, traditional practices continued, particularly in the rural populations. Conclusions: Differences in knowledge, beliefs and behaviors were apparent between the two series. Despite widespread rudimentary knowledge of disease prevention, targeted education might benefit both communities, particularly basic hygiene education for rural communities. Healthcare access should also be improved for rural populations. The impact of these measures could be assessed by future fieldwork.

Published
2015

13. Inverse relationship between microRNA-155 and -184 expression with increasing conjunctival inflammation during ocular Chlamydia trachomatis infection

Author

Derrick, Tamsyn, primary, Last, Anna R., additional, Burr, Sarah E., additional, Roberts, Chrissy h., additional, Nabicassa, Meno, additional, Cassama, Eunice, additional, Bailey, Robin L., additional, Mabey, David C. W., additional, Burton, Matthew J., additional, and Holland, Martin J., additional

Published
2015
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15. Development and Evaluation of a Next-Generation Digital PCR Diagnostic Assay for Ocular Chlamydia trachomatis Infections

Author

Roberts, Chrissy h., primary, Last, Anna, additional, Molina-Gonzalez, Sandra, additional, Cassama, Eunice, additional, Butcher, Robert, additional, Nabicassa, Meno, additional, McCarthy, Elizabeth, additional, Burr, Sarah E., additional, Mabey, David C., additional, Bailey, Robin L., additional, and Holland, Martin J., additional

Published
2013
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16. 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.

Author

Goncalves, Adriana, Makalo, Pateh, Joof, Hassan, Burr, Sarah, Ramadhani, Athumani, Massae, Patrick, Malisa, Aiweda, Mtuy, Tara, Derrick, Tamsyn, Last, Anna, Nabicassa, Meno, Cassama, Eunice, Houghton, Joanna, Palmer, Christine, Pickering, Harry, Burton, Matthew, Mabey, David, Bailey, Robin, Goodier, Martin, and Holland, Martin

Subjects
GENOTYPES, SINGLE nucleotide polymorphisms, CHLAMYDIA trachomatis, CONJUNCTIVA diseases, SCARS
Abstract

NKG2C is an activating receptor that is preferentially expressed on natural killer (NK) cells. The gene encoding NKG2C (killer cell lectin-like receptor C2, KLRC2) is present at different copy numbers in the genomes of different individuals. Deletion at the NKG2C locus was investigated in a case-control study of 1522 individuals indigenous to East- and West-Africa and the association with the ocular Chlamydia trachomatis infection and its sequelae was explored. The frequency of homozygous KLRC2 deletion was 13.7 % in Gambians and 4.7 % in Tanzanians. A significantly higher frequency of the deletion allele was found in West-Africans from the Gambia and Guinea-Bissau (36.2 % p = 2.105 × 10, 26.8 % p = 0.050; respectively) in comparison to East-African Tanzanians where the frequency of the deletion is comparable to other human populations (20.9 %). We found no evidence for an association between the numbers of KLRC2 gene copies and the clinical manifestations of trachoma (follicular trachoma or conjunctival scarring). A new method for imputation of KLRC2 genotypes from single nucleotide polymorphism (SNP) data in 2621 individuals from the Gambia further confirmed these results. Our data suggest that NKG2C does not play a major role in trachomatous disease. We found that the deletion allele is present at different frequencies in different populations but the reason behind these differences is currently not understood. The new method offers the potential to use SNP arrays from genome wide association studies to study the frequency of KLRC2 deletion in other populations and its association with other diseases. [ABSTRACT FROM AUTHOR]

Published
2016
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17. Inverse relationship between microRNA-155 and -184 expression with increasing conjunctival inflammation during ocular Chlamydia trachomatis infection.

Author

Derrick, Tamsyn, Last, Anna R., Burr, Sarah E., Roberts, Chrissy h., Nabicassa, Meno, Cassama, Eunice, Bailey, Robin L., Mabey, David C. W., Burton, Matthew J., and Holland, Martin J.

Subjects
MICRORNA, RNA, CONJUNCTIVA, ADNEXA oculi, CHLAMYDIA trachomatis
Abstract

Background: Trachoma, a preventable blinding eye disease, is initiated by ocular infection with Chlamydia trachomatis (Ct). We previously showed that microRNAs (miR) -147b and miR-1285 were up-regulated in inflammatory trachomatous scarring. During the initial stage of disease, follicular trachoma with current Ct infection, the differential expression of miR has not yet been investigated.Methods: Conjunctival samples were collected from 163 children aged 1-9 years old living in a trachoma-endemic region of Guinea Bissau, West Africa. Small RNA sequencing (RNAseq) was carried out on samples from five children with follicular trachoma and current Ct infection and five children with healthy conjunctivae and no Ct infection. Small RNAseq was also carried out on human epithelial cell lines infected with ocular Ct strains A2497 and isogenic plasmid-free A2497 in vitro. Results were validated by quantitative PCR (qPCR) in 163 clinical samples.Results: Differential expression of RNAseq data identified 12 miR with changes in relative expression during follicular trachoma, of which 9 were confirmed as differentially expressed by qPCR (miR-155, miR-150, miR-142, miR-181b, miR-181a, miR-342, miR-132, miR-4728 and miR-184). MiR-155 and miR-184 expression had a direct relationship with the degree of clinical inflammation. MiR-155 was up-regulated (OR = 2.533 ((95 % CI = 1.291-4.971); P = 0.0069) and miR-184 was down-regulated (OR = 0.416 ((95 % CI = 0.300-0.578); P = 1.61*10(-7)) as the severity of clinical inflammation increased. Differential miR expression was not detected in HEp-2 or HCjE epithelial cells 48 h post infection with Ct in vitro. HCjE cells, a conjunctival epithelial cell line, had a markedly different miR background expression compared to HEp-2 cells.Conclusions: In follicular trachoma, expression of miR-155 and miR-184 is correlated with the severity of inflammation. This likely reflects host regulation of the immune response and a prolonged period of wound healing following the clearance of Ct. Prolonged healing may be associated with subsequent development of scarring trachoma. [ABSTRACT FROM AUTHOR]

Published
2016
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18. Risk Factors for Active Trachoma and Ocular Chlamydia trachomatis Infection in Treatment-Naïve Trachoma-Hyperendemic Communities of the Bijagós Archipelago, Guinea Bissau.

Author

Last, Anna R., Burr, Sarah E., Weiss, Helen A., Harding-Esch, Emma M., Cassama, Eunice, Nabicassa, Meno, Mabey, David C., Holland, Martin J., and Bailey, Robin L.

Subjects
TRACHOMA treatment, CHLAMYDIA infections, CHLAMYDIA trachomatis, DISEASE risk factors
Abstract

Background: Trachoma, caused by ocular infection with Chlamydia trachomatis, is hyperendemic on the Bijagós Archipelago of Guinea Bissau. An understanding of the risk factors associated with active trachoma and infection on these remote and isolated islands, which are atypical of trachoma-endemic environments described elsewhere, is crucial to the implementation of trachoma elimination strategies. Methodology/Principal Findings: A cross-sectional population-based trachoma prevalence survey was conducted on four islands. We conducted a questionnaire-based risk factor survey, examined participants for trachoma using the World Health Organization (WHO) simplified grading system and collected conjunctival swab samples for 1507 participants from 293 randomly selected households. DNA extracted from conjunctival swabs was tested using the Roche Amplicor CT/NG PCR assay. The prevalence of active (follicular and/or inflammatory) trachoma was 11% (167/1508) overall and 22% (136/618) in 1–9 year olds. The prevalence of C. trachomatis infection was 18% overall and 25% in 1–9 year olds. There were strong independent associations of active trachoma with ocular and nasal discharge, C. trachomatis infection, young age, male gender and type of household water source. C. trachomatis infection was independently associated with young age, ocular discharge, type of household water source and the presence of flies around a latrine. Conclusions/Significance: In this remote island environment, household-level risk factors relating to fly populations, hygiene behaviours and water usage are likely to be important in the transmission of ocular C. trachomatis infection and the prevalence of active trachoma. This may be important in the implementation of environmental measures in trachoma control. [ABSTRACT FROM AUTHOR]

Published
2014
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19. Additional file 5: of Inverse relationship between microRNA-155 and -184 expression with increasing conjunctival inflammation during ocular Chlamydia trachomatis infection

Author

Tamsyn Derrick, Last, Anna, Burr, Sarah, Roberts, Chrissy, Nabicassa, Meno, Cassama, Eunice, Bailey, Robin, Mabey, David, Burton, Matthew, and Holland, Martin

Subjects
sense organs, eye diseases, 3. Good health
Abstract

Relative abundance of miR in the conjunctiva of cases of follicular trachoma (TF) and controls (N). MiR with a mean read count in TF cases or controlsâ

20. Additional file 8: of Inverse relationship between microRNA-155 and -184 expression with increasing conjunctival inflammation during ocular Chlamydia trachomatis infection

Author

Tamsyn Derrick, Last, Anna, Burr, Sarah, Roberts, Chrissy, Nabicassa, Meno, Cassama, Eunice, Bailey, Robin, Mabey, David, Burton, Matthew, and Holland, Martin

Subjects
body regions, endocrine system, nervous system, fungi, eye diseases, 3. Good health
Abstract

Focused list of published roles for miR that are differentially expressed in follicular trachoma that relate to inflammation or fibrosis. (PDF 59Â kb)

21. Additional file 5: of Inverse relationship between microRNA-155 and -184 expression with increasing conjunctival inflammation during ocular Chlamydia trachomatis infection

Author

Tamsyn Derrick, Last, Anna, Burr, Sarah, Roberts, Chrissy, Nabicassa, Meno, Cassama, Eunice, Bailey, Robin, Mabey, David, Burton, Matthew, and Holland, Martin

Subjects
sense organs, eye diseases, 3. Good health
Abstract

Relative abundance of miR in the conjunctiva of cases of follicular trachoma (TF) and controls (N). MiR with a mean read count in TF cases or controlsâ

22. Additional file 1: of Inverse relationship between microRNA-155 and -184 expression with increasing conjunctival inflammation during ocular Chlamydia trachomatis infection

Author

Tamsyn Derrick, Last, Anna, Burr, Sarah, Roberts, Chrissy, Nabicassa, Meno, Cassama, Eunice, Bailey, Robin, Mabey, David, Burton, Matthew, and Holland, Martin

Subjects
3. Good health
Abstract

Chlamydial infection of HEp-2 and HCjE cell lines with three ocular Ct strains. HEp-2 cell monolayers infected with Ct strains A2497 (A), A2497P- (B) and A/HAR-13 (C), and HCjE cell monolayers infected with Ct strains A2497 (D), A2497P- (E) and A/HAR-13 (F) at 48 hpi. Cell nuclei are stained with DAPI (blue) and Ct inclusions are stained with anti-C. trachomatis MOMP antibody (FITC (green)). Cells were infected with an MOI of 1 and viewed at 40X magnification. Representative photographs were taken from one of three replicates for each condition. (PDF 770Â kb)

23. Inverse relationship between microRNA-155 and -184 expression with increasing conjunctival inflammation during ocular Chlamydia trachomatis infection

Author

Derrick, Tamsyn, Last, Anna R, Burr, Sarah E, Roberts, Chrissy H, Nabicassa, Meno, Cassama, Eunice, Bailey, Robin L, Mabey, David CW, Burton, Matthew J, and Holland, Martin J

Subjects
Infectious Diseases
Abstract

BACKGROUND: Trachoma, a preventable blinding eye disease, is initiated by ocular infection with Chlamydia trachomatis (Ct). We previously showed that microRNAs (miR) -147b and miR-1285 were up-regulated in inflammatory trachomatous scarring. During the initial stage of disease, follicular trachoma with current Ct infection, the differential expression of miR has not yet been investigated. METHODS: Conjunctival samples were collected from 163 children aged 1-9 years old living in a trachoma-endemic region of Guinea Bissau, West Africa. Small RNA sequencing (RNAseq) was carried out on samples from five children with follicular trachoma and current Ct infection and five children with healthy conjunctivae and no Ct infection. Small RNAseq was also carried out on human epithelial cell lines infected with ocular Ct strains A2497 and isogenic plasmid-free A2497 in vitro. Results were validated by quantitative PCR (qPCR) in 163 clinical samples. RESULTS: Differential expression of RNAseq data identified 12 miR with changes in relative expression during follicular trachoma, of which 9 were confirmed as differentially expressed by qPCR (miR-155, miR-150, miR-142, miR-181b, miR-181a, miR-342, miR-132, miR-4728 and miR-184). MiR-155 and miR-184 expression had a direct relationship with the degree of clinical inflammation. MiR-155 was up-regulated (OR = 2.533 ((95 % CI = 1.291-4.971); P = 0.0069) and miR-184 was down-regulated (OR = 0.416 ((95 % CI = 0.300-0.578); P = 1.61*10(-7)) as the severity of clinical inflammation increased. Differential miR expression was not detected in HEp-2 or HCjE epithelial cells 48 h post infection with Ct in vitro. HCjE cells, a conjunctival epithelial cell line, had a markedly different miR background expression compared to HEp-2 cells. CONCLUSIONS: In follicular trachoma, expression of miR-155 and miR-184 is correlated with the severity of inflammation. This likely reflects host regulation of the immune response and a prolonged period of wound healing following the clearance of Ct. Prolonged healing may be associated with subsequent development of scarring trachoma.

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24. Additional file 8: of Inverse relationship between microRNA-155 and -184 expression with increasing conjunctival inflammation during ocular Chlamydia trachomatis infection

Author

Tamsyn Derrick, Last, Anna, Burr, Sarah, Roberts, Chrissy, Nabicassa, Meno, Cassama, Eunice, Bailey, Robin, Mabey, David, Burton, Matthew, and Holland, Martin

Subjects
body regions, endocrine system, nervous system, fungi, eye diseases, 3. Good health
Abstract

Focused list of published roles for miR that are differentially expressed in follicular trachoma that relate to inflammation or fibrosis. (PDF 59Â kb)

25. Additional file 1: of Inverse relationship between microRNA-155 and -184 expression with increasing conjunctival inflammation during ocular Chlamydia trachomatis infection

Author

Tamsyn Derrick, Last, Anna, Burr, Sarah, Roberts, Chrissy, Nabicassa, Meno, Cassama, Eunice, Bailey, Robin, Mabey, David, Burton, Matthew, and Holland, Martin

Subjects
3. Good health
Abstract

Chlamydial infection of HEp-2 and HCjE cell lines with three ocular Ct strains. HEp-2 cell monolayers infected with Ct strains A2497 (A), A2497P- (B) and A/HAR-13 (C), and HCjE cell monolayers infected with Ct strains A2497 (D), A2497P- (E) and A/HAR-13 (F) at 48 hpi. Cell nuclei are stained with DAPI (blue) and Ct inclusions are stained with anti-C. trachomatis MOMP antibody (FITC (green)). Cells were infected with an MOI of 1 and viewed at 40X magnification. Representative photographs were taken from one of three replicates for each condition. (PDF 770Â kb)

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