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147 results on '"Molloy, Síle F."'

1. Reduction in mortality from HIV-related CNS infections in routine care in Africa (DREAMM): a before-and-after, implementation study

Author

Mfinanga, Sayoki, Kanyama, Cecilia, Kouanfack, Charles, Nyirenda, Saulos, Kivuyo, Sokoine Lesikari, Boyer-Chammard, Timothée, Phiri, Sam, Ngoma, Jonathon, Shimwela, Meshack, Nkungu, Daniel, Fomete, Lauriane Nomene, Simbauranga, Rehema, Chawinga, Chimwemwe, Ngakam, Nicaine, Heller, Tom, Lontsi, Sandrine Sa’a, Aghakishiyeva, Elnara, Jalava, Katri, Fuller, Sebastian, Reid, Anne-Marie, Rajasingham, Radha, Lawrence, David S, Hosseinipour, Mina C, Beaumont, Emma, Bradley, John, Jaffar, Shabbar, Lortholary, Olivier, Harrison, Thomas, Molloy, Síle F, Sturny-Leclère, Aude, and Loyse, Angela

Published
2023
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2. Cost-effectiveness of single, high-dose, liposomal amphotericin regimen for HIV-associated cryptococcal meningitis in five countries in sub-Saharan Africa: an economic analysis of the AMBITION-cm trial

Author

Goodall, Jack, Lechiile, Kwana, Mawoko, Norah, Mbangiwa, Tshepiso, Milburn, James, Mmipi, Refilwe, Ponatshego, Ponego, Rulaganyang, Ikanyang, Seatla, Kaelo, Siamisang, Keatlaretse, Tlhako, Nametso, Tsholo, Katlego, April, Samantha, Bekiswa, Abulele, Boloko, Linda, Bookholane, Hloni, Crede, Thomas, Davids, Lee-Ann, Goliath, Rene, Hlungulu, Siphokazi, Hoffman, Regina, Kyepa, Henriette, Masina, Noma, Maughan, Deborah, Mnguni, Trevor, Moosa, Sumaiyya, Morar, Tania, Mpalali, Mkanyiseli, Naude, Jonathan, Oliphant, Ida, Singh, Achita, Sayed, Sumaya, Sebesho, Leago, Shey, Muki, Swanepoel, Loraine, Chasweka, Madalitso, Chimang'anga, Wezi, Chimphambano, Tipatseni, Gondwe, Ebbie, Mzinganjira, Henry, Kadzilimbile, Aubrey, Kateta, Steven, Kossam, Evelyn, Kukacha, Christopher, Lipenga, Bright, Ndaferankhande, John, Ndalama, Maureen, Shah, Reya, Singini, Andreas, Stott, Katherine, Zambasa, Agness, Banda, Towera, Chikaonda, Tarsizio, Chitulo, Gladys, Chiwoko, Lorren, Chome, Nelecy, Gwin, Mary, Kachitosi, Timothy, Kamanga, Beauty, Kazembe, Mussah, Kumwenda, Emily, Kumwenda, Masida, Maya, Chimwemwe, Mhango, Wilberforce, Mphande, Chimwemwe, Msumba, Lusungu, Munthali, Tapiwa, Ngoma, Doris, Nicholas, Simon, Simwinga, Lusayo, Stambuli, Anthony, Tegha, Gerald, Zambezi, Janet, Ahimbisibwe, Cynthia, Akampurira, Andrew, Alice, Anamudde, Cresswell, Fiona, Gakuru, Jane, Kagimu, Enock, Kasibante, John, Kiiza, Daniel, Kisembo, John, Kwizera, Richard, Kugonza, Florence, Laker, Eva, Luggya, Tonny, Lule, Andrew, Musubire, Abdu, Muyise, Rhona, Namujju, Carol Olivie, Ndyetukira, Jane Francis, Nsangi, Laura, Okirworth, Michael, Rhein, Joshua, Rutakingirwa, Morris K, Sadiq, Alisat, Ssebambulidde, Kenneth, Tadeo, Kiiza, Tukundane, Asmus, Atwine, Leo, Buzaare, Peter, Collins, Muganzi, Emily, Ninsima, Inyakuwa, Christine, Kariisa, Samson, Mwesigye, James, Nuwamanya, Simpson, Rodgers, Ankunda, Rukundo, Joan, Rwomushana, Irene, Ssemusu, Mike, Stead, Gavin, Boyd, Kathyrn, Gondo, Secrecy, Kufa, Prosper, Makaha, Edward, Moyo, Colombus, Mtisi, Takudzwa, Mudzinga, Shepherd, Mutata, Constantine, Mwarumba, Taddy, Zinyandu, Tawanda, Alanio, Alexandre, Dromer, Francoise, Lortholary, Olivier, Sturny-Leclere, Aude, Griffin, Philippa, Hafeez, Sophia, Loyse, Angela, van Widenfelt, Erik, Lawrence, David S, Muthoga, Charles, Meya, David B, Tugume, Lillian, Williams, Darlisha, Rajasingham, Radha, Boulware, David R, Mwandumba, Henry C, Moyo, Melanie, Dziwani, Eltas N, Maheswaran, Hendramoorthy, Kanyama, Cecilia, Hosseinipour, Mina C, Chawinga, Chimwemwe, Meintjes, Graeme, Schutz, Charlotte, Comins, Kyla, Bango, Funeka, Muzoora, Conrad, Jjunju, Samuel, Nuwagira, Edwin, Mosepele, Mosepele, Leeme, Tshepo, Ndhlovu, Chiratidzo E, Hlupeni, Admire, Shamu, Shepherd, Boyer-Chammard, Timothée, Molloy, Síle F, Youssouf, Nabila, Chen, Tao, Shiri, Tinevimbo, Jaffar, Shabbar, Harrison, Thomas S, Jarvis, Joseph N, and Niessen, Louis W

Published
2022
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5. Leave no one behind: response to new evidence and guidelines for the management of cryptococcal meningitis in low-income and middle-income countries

Author

Loyse, Angela, Burry, Jessica, Cohn, Jennifer, Ford, Nathan, Chiller, Tom, Ribeiro, Isabela, Koulla-Shiro, Sinata, Mghamba, Janneth, Ramadhani, Angela, Nyirenda, Rose, Aliyu, Sani H, Wilson, Douglas, Le, Thuy, Oladele, Rita, Lesikari, Sokoine, Muzoora, Conrad, Kalata, Newton, Temfack, Elvis, Mapoure, Yacouba, Sini, Victor, Chanda, Duncan, Shimwela, Meshack, Lakhi, Shabir, Ngoma, Jonathon, Gondwe-Chunda, Lilian, Perfect, Chase, Shroufi, Amir, Andrieux-Meyer, Isabelle, Chan, Adrienne, Schutz, Charlotte, Hosseinipour, Mina, Van der Horst, Charles, Klausner, Jeffrey D, Boulware, David R, Heyderman, Robert, Lalloo, David, Day, Jeremy, Jarvis, Joseph N, Rodrigues, Marcio, Jaffar, Shabbar, Denning, David, Migone, Chantal, Doherty, Megan, Lortholary, Olivier, Dromer, Françoise, Stack, Muirgen, Molloy, Síle F, Bicanic, Tihana, van Oosterhout, Joep, Mwaba, Peter, Kanyama, Cecilia, Kouanfack, Charles, Mfinanga, Sayoki, Govender, Nelesh, and Harrison, Thomas S

Published
2019
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6. Genetic diversity and microevolution in clinical Cryptococcus isolates from Cameroon

Author

Sephton-Clark, Poppy, primary, Temfack, Elvis, additional, Tenor, Jennifer L, additional, Toffaletti, Dena L, additional, Loyse, Angela, additional, Molloy, Síle F, additional, Perfect, John R, additional, Bicanic, Tihana, additional, Harrison, Thomas S, additional, Lortholary, Olivier, additional, Kouanfack, Charles, additional, and Cuomo, Christina A, additional

Published
2023
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8. COVID-19-associated pulmonary aspergillosis in mechanically ventilated patients: a prospective, multicentre UK study

Author

Hurt, William, primary, Youngs, Jonathan, additional, Ball, Jonathan, additional, Edgeworth, Jonathan, additional, Hopkins, Philip, additional, Jenkins, David R, additional, Leaver, Susannah, additional, Mazzella, Andrea, additional, Molloy, Síle F, additional, Schelenz, Silke, additional, Wise, Matt P, additional, White, P Lewis, additional, Yusuff, Hakeem, additional, Wyncoll, Duncan, additional, and Bicanic, Tihana, additional

Published
2023
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10. A pragmatic approach to managing antiretroviral therapy-experienced patients diagnosed with HIV-associated cryptococcal meningitis: impact of antiretroviral therapy adherence and duration

Author

Alufandika, Melanie, Lawrence, David S., Boyer-Chammard, Timothée, Kanyama, Cecilia, Ndhlovu, Chiratidzo E., Mosepele, Mosepele, Tugume, Lillian, Meya, David, Boulware, David R., Rhein, Joshua, Muzoora, Conrad, Youssouf, Nabila, Molloy, Síle F., Schutz, Charlotte, Lortholary, Olivier, Meintjes, Graeme, Mwandumba, Henry C., Harrison, Thomas S., and Jarvis, Joseph N.

Published
2020
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11. Correction to: AMBIsome Therapy Induction OptimisatioN (AMBITION): High Dose AmBisome for Cryptococcal Meningitis Induction Therapy in sub-Saharan Africa: Study Protocol for a Phase 3 Randomised Controlled Non-Inferiority Trial

Author

Lawrence, David S., Youssouf, Nabila, Molloy, Síle F., Alanio, Alexandre, Alufandika, Melanie, Boulware, David R., Boyer-Chammard, Timothée, Chen, Tao, Dromer, Francoise, Hlupeni, Admire, Hope, William, Hosseinipour, Mina C., Kanyama, Cecilia, Lortholary, Oliver, Loyse, Angela, Meya, David B., Mosepele, Mosepele, Muzoora, Conrad, Mwandumba, Henry C., Ndhlovu, Chiratidzo E., Niessen, Louis, Schutz, Charlotte, Stott, Katharine E., Wang, Duolao, Lalloo, David G., Meintjes, Graeme, Jaffar, Shabbar, Harrison, Thomas S., and Jarvis, Joseph N.

Published
2019
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12. Genomic Variation across a Clinical Cryptococcus Population Linked to Disease Outcome

Author

Sephton-Clark, Poppy, primary, Tenor, Jennifer L., additional, Toffaletti, Dena L., additional, Meyers, Nancy, additional, Giamberardino, Charles, additional, Molloy, Síle F., additional, Palmucci, Julia R., additional, Chan, Adrienne, additional, Chikaonda, Tarsizio, additional, Heyderman, Robert, additional, Hosseinipour, Mina, additional, Kalata, Newton, additional, Kanyama, Cecilia, additional, Kukacha, Christopher, additional, Lupiya, Duncan, additional, Mwandumba, Henry C., additional, Harrison, Thomas, additional, Bicanic, Tihana, additional, Perfect, John R., additional, and Cuomo, Christina A., additional

Published
2022
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13. Cost-effectiveness of single, high-dose, liposomal amphotericin regimen for HIV-associated cryptococcal meningitis in five countries in sub-Saharan Africa: an economic analysis of the AMBITION-cm trial

Author

Lawrence, David S, primary, Muthoga, Charles, additional, Meya, David B, additional, Tugume, Lillian, additional, Williams, Darlisha, additional, Rajasingham, Radha, additional, Boulware, David R, additional, Mwandumba, Henry C, additional, Moyo, Melanie, additional, Dziwani, Eltas N, additional, Maheswaran, Hendramoorthy, additional, Kanyama, Cecilia, additional, Hosseinipour, Mina C, additional, Chawinga, Chimwemwe, additional, Meintjes, Graeme, additional, Schutz, Charlotte, additional, Comins, Kyla, additional, Bango, Funeka, additional, Muzoora, Conrad, additional, Jjunju, Samuel, additional, Nuwagira, Edwin, additional, Mosepele, Mosepele, additional, Leeme, Tshepo, additional, Ndhlovu, Chiratidzo E, additional, Hlupeni, Admire, additional, Shamu, Shepherd, additional, Boyer-Chammard, Timothée, additional, Molloy, Síle F, additional, Youssouf, Nabila, additional, Chen, Tao, additional, Shiri, Tinevimbo, additional, Jaffar, Shabbar, additional, Harrison, Thomas S, additional, Jarvis, Joseph N, additional, Niessen, Louis W, additional, Goodall, Jack, additional, Lechiile, Kwana, additional, Mawoko, Norah, additional, Mbangiwa, Tshepiso, additional, Milburn, James, additional, Mmipi, Refilwe, additional, Ponatshego, Ponego, additional, Rulaganyang, Ikanyang, additional, Seatla, Kaelo, additional, Siamisang, Keatlaretse, additional, Tlhako, Nametso, additional, Tsholo, Katlego, additional, April, Samantha, additional, Bekiswa, Abulele, additional, Boloko, Linda, additional, Bookholane, Hloni, additional, Crede, Thomas, additional, Davids, Lee-Ann, additional, Goliath, Rene, additional, Hlungulu, Siphokazi, additional, Hoffman, Regina, additional, Kyepa, Henriette, additional, Masina, Noma, additional, Maughan, Deborah, additional, Mnguni, Trevor, additional, Moosa, Sumaiyya, additional, Morar, Tania, additional, Mpalali, Mkanyiseli, additional, Naude, Jonathan, additional, Oliphant, Ida, additional, Singh, Achita, additional, Sayed, Sumaya, additional, Sebesho, Leago, additional, Shey, Muki, additional, Swanepoel, Loraine, additional, Chasweka, Madalitso, additional, Chimang'anga, Wezi, additional, Chimphambano, Tipatseni, additional, Gondwe, Ebbie, additional, Mzinganjira, Henry, additional, Kadzilimbile, Aubrey, additional, Kateta, Steven, additional, Kossam, Evelyn, additional, Kukacha, Christopher, additional, Lipenga, Bright, additional, Ndaferankhande, John, additional, Ndalama, Maureen, additional, Shah, Reya, additional, Singini, Andreas, additional, Stott, Katherine, additional, Zambasa, Agness, additional, Banda, Towera, additional, Chikaonda, Tarsizio, additional, Chitulo, Gladys, additional, Chiwoko, Lorren, additional, Chome, Nelecy, additional, Gwin, Mary, additional, Kachitosi, Timothy, additional, Kamanga, Beauty, additional, Kazembe, Mussah, additional, Kumwenda, Emily, additional, Kumwenda, Masida, additional, Maya, Chimwemwe, additional, Mhango, Wilberforce, additional, Mphande, Chimwemwe, additional, Msumba, Lusungu, additional, Munthali, Tapiwa, additional, Ngoma, Doris, additional, Nicholas, Simon, additional, Simwinga, Lusayo, additional, Stambuli, Anthony, additional, Tegha, Gerald, additional, Zambezi, Janet, additional, Ahimbisibwe, Cynthia, additional, Akampurira, Andrew, additional, Alice, Anamudde, additional, Cresswell, Fiona, additional, Gakuru, Jane, additional, Kagimu, Enock, additional, Kasibante, John, additional, Kiiza, Daniel, additional, Kisembo, John, additional, Kwizera, Richard, additional, Kugonza, Florence, additional, Laker, Eva, additional, Luggya, Tonny, additional, Lule, Andrew, additional, Musubire, Abdu, additional, Muyise, Rhona, additional, Namujju, Carol Olivie, additional, Ndyetukira, Jane Francis, additional, Nsangi, Laura, additional, Okirworth, Michael, additional, Rhein, Joshua, additional, Rutakingirwa, Morris K, additional, Sadiq, Alisat, additional, Ssebambulidde, Kenneth, additional, Tadeo, Kiiza, additional, Tukundane, Asmus, additional, Atwine, Leo, additional, Buzaare, Peter, additional, Collins, Muganzi, additional, Emily, Ninsima, additional, Inyakuwa, Christine, additional, Kariisa, Samson, additional, Mwesigye, James, additional, Nuwamanya, Simpson, additional, Rodgers, Ankunda, additional, Rukundo, Joan, additional, Rwomushana, Irene, additional, Ssemusu, Mike, additional, Stead, Gavin, additional, Boyd, Kathyrn, additional, Gondo, Secrecy, additional, Kufa, Prosper, additional, Makaha, Edward, additional, Moyo, Colombus, additional, Mtisi, Takudzwa, additional, Mudzinga, Shepherd, additional, Mutata, Constantine, additional, Mwarumba, Taddy, additional, Zinyandu, Tawanda, additional, Alanio, Alexandre, additional, Dromer, Francoise, additional, Lortholary, Olivier, additional, Sturny-Leclere, Aude, additional, Griffin, Philippa, additional, Hafeez, Sophia, additional, Loyse, Angela, additional, and van Widenfelt, Erik, additional

Published
2022
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15. Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa

Author

Molloy, Síle F., Kanyama, Cecilia, Heyderman, Robert S., Loyse, Angela, Kouanfack, Charles, Chanda, Duncan, Mfinanga, Sayoki, Temfack, Elvis, Lakhi, Shabir, Lesikari, Sokoine, Chan, Adrienne K., Stone, Neil, Kalata, Newton, Karunaharan, Natasha, Gaskell, Kate, Peirse, Mary, Ellis, Jayne, Chawinga, Chimwemwe, Lontsi, Sandrine, Ndong, Jean-Gilbert, Bright, Philip, Lupiya, Duncan, Chen, Tao, Bradley, John, Adams, Jack, van der Horst, Charles, van Oosterhout, Joep J., Sini, Victor, Mapoure, Yacouba N., Mwaba, Peter, Bicanic, Tihana, Lalloo, David G., Wang, Duolao, Hosseinipour, Mina C., Lortholary, Olivier, Jaffar, Shabbar, and Harrison, Thomas S.

Published
2018
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16. AMBIsome Therapy Induction OptimisatioN (AMBITION): High Dose AmBisome for Cryptococcal Meningitis Induction Therapy in sub-Saharan Africa: Study Protocol for a Phase 3 Randomised Controlled Non-Inferiority Trial

Author

Lawrence, David S., Youssouf, Nabila, Molloy, Síle F., Alanio, Alexandre, Alufandika, Melanie, Boulware, David R., Boyer-Chammard, Timothée, Chen, Tao, Dromer, Francoise, Hlupeni, Admire, Hope, William, Hosseinipour, Mina C., Kanyama, Cecilia, Lortholary, Oliver, Loyse, Angela, Meya, David B., Mosepele, Mosepele, Muzoora, Conrad, Mwandumba, Henry C., Ndhlovu, Chiratidzo E., Niessen, Louis, Schutz, Charlotte, Stott, Katharine E., Wang, Duolao, Lalloo, David G., Meintjes, Graeme, Jaffar, Shabbar, Harrison, Thomas S., and Jarvis, Joseph N.

Published
2018
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19. Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis

Author

Jarvis, Joseph N, Lawrence, David S, Meya, David B, Kagimu, Enock, Kasibante, John, Mpoza, Edward, Rutakingirwa, Morris K, Ssebambulidde, Kenneth, Tugume, Lillian, Rhein, Joshua, Boulware, David R, Mwandumba, Henry C, Moyo, Melanie, Mzinganjira, Henry, Kanyama, Cecilia, Hosseinipour, Mina C, Chawinga, Chimwemwe, Meintjes, Graeme, Schutz, Charlotte, Comins, Kyla, Singh, Achita, Muzoora, Conrad, Jjunju, Samuel, Nuwagira, Edwin, Mosepele, Mosepele, Leeme, Tshepo, Siamisang, Keatlaretse, Ndhlovu, Chiratidzo E, Hlupeni, Admire, Mutata, Constantine, van Widenfelt, Erik, Chen, Tao, Wang, Duolao, Hope, William, Boyer-Chammard, Timothée, Loyse, Angela, Molloy, Síle F, Youssouf, Nabila, Lortholary, Olivier, Lalloo, David G, Jaffar, Shabbar, Harrison, Thomas S, Ambition Study Group, London School of Hygiene and Tropical Medicine (LSHTM), Bostwana Harvard AIDS Institute Partneship Gaborone, National Center for Atmospheric Research [Boulder] (NCAR), University of North Carolina Project-Malawi (UNC Project), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), University of Cape Town, Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris]-Université Paris Cité (UPC), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Supported by a grant (TRIA2015-1092) through the European and Developing Countries Clinical Trials Partnership, with assistance from the Swedish International Development Cooperation Agency, as well as by funding from the U.K. Department of Health and Social Care, the U.K. Foreign Commonwealth and Development Office, the U.K. Medical Research Council, and Wellcome Trust, through the Joint Global Health Trials scheme (MR/P006922/1). Funding was also provided by the National Institute for Health Research (NIHR) through a Global Health Research Professorship (RP-2017-08-ST2-012, to Dr. Jarvis) with aid from the U.K. government to support global health research. Dr. Meintjes was supported by grants (098316, 214321/Z/18/Z, and 203135/Z/16/Z) from the Wellcome Trust and a grant (64787) from the South African Research Chairs Initiative of the Department of Science and Technology and the National Research Foundation of South Africa. Diagnostic testing in Uganda was supported by a grant (R01NS086312) from the National Institute of Neurological Disorders and Stroke. Dr. Rhein was supported by a grant (K01 TW010268) from the Fogarty International Center. Liposomal amphotericin B (AmBisome) was donated by Gilead Sciences., We thank the trial participants and their families and caregivers, as well as all the clinical, laboratory, and administrative staff at all the sites who were not directly involved in the trial, Andrew Nunn, Sayoki Mfinanga, Robert Peck, and William Powderly for serving on the data and safety monitoring committee, and John Perfect, Andrew Kambugu, Saidi Kapigi, and Douglas Wilson for serving on the trial steering committee. We dedicate the trial to the memory of Siphokazi Hlungulu, who worked as a research nurse and study coordinator for the Cape Town Ambition site for the duration of the trial and died before seeing the results published., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)

Subjects
wl_200, qv_350, General Medicine, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, wc_245
Abstract

BackgroundCryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)-related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known.MethodsIn this phase 3 randomized, controlled, noninferiority trial conducted in five African countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization-recommended treatment, which includes amphotericin B deoxycholate (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin.ResultsA total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 participants (24.8%; 95% confidence interval [CI], 20.7 to 29.3) in the liposomal amphotericin B group and 117 (28.7%; 95% CI, 24.4 to 33.4) in the control group (difference, -3.9 percentage points); the upper boundary of the one-sided 95% confidence interval was 1.2 percentage points (within the noninferiority margin; P10 colony-forming units (CFU) per milliliter per day in the liposomal amphotericin B group and -0.42 log10 CFU per milliliter per day in the control group. Fewer participants had grade 3 or 4 adverse events in the liposomal amphotericin B group than in the control group (50.0% vs. 62.3%).ConclusionsSingle-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-associated cryptococcal meningitis and was associated with fewer adverse events. (Funded by the European and Developing Countries Clinical Trials Partnership and others; Ambition ISRCTN number, ISRCTN72509687.).

Published
2022
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22. Short term mortality outcomes of HIV-associated Cryptococcal meningitis in antiretroviral therapy naïve and experienced patients in sub-Saharan Africa

Author

Kalata, Newton, Ellis, Jayne, Kanyama, Cecilia, Kuoanfank, Charles, Temfack, Elvis, Mfinanga, Sayoki, Lesikari, Sokoine, Chanda, Duncan, Lakhi, Shabir, Nyazika, Tinashe, Chan, Adrienne K, van Oosterhout, Joep J, Chen, Tao, Hosseinipour, Mina C, Lortholary, Olivier, Wang, Duolao, Jaffar, Shabbar, Loyse, Angela, Heyderman, Robert S, Harrison, Thomas S, and Molloy, Síle F

Subjects
qv_268.5, wl_200, wa_395, wc_503
Abstract

Background\ud An increasing proportion of patients with HIV-associated cryptococcal meningitis have received antiretroviral therapy (ART) prior to presentation. There is some evidence suggesting an increased two-week mortality in those receiving ART for less than 14 days compared with those on ART for more than 14 days. However, presentation and outcomes for cryptococcal meningitis patients who have recently initiated ART, and those with virologic failure and/or non-adherence are not well described.\ud \ud Methods\ud 678 adults with first episode of cryptococcal meningitis recruited into a randomized, non-inferiority, multicentre phase 3 trial in 4 sub-Saharan countries were analysed to compare clinical presentation and 2-and 10-week mortality outcomes between ART-naive and experienced patients, and between patients receiving ART for varying durations prior to presentation.\ud \ud Results\ud Over half (56% (381/678)) the study participants diagnosed with a first episode of cryptococcal meningitis were ART-experienced. All-cause mortality was similar at 2-weeks (17% vs 20%; HR 0.85, 95%CI 0.6-1.2, p=0.35), and 10 weeks (38% vs 36%; HR 1.03, 95%CI 0.8-1.32, p=0.82) for ART-experienced vs ART-naïve patients, respectively. Among ART-experienced patients, using different cut-off points for ART duration, there were no significant differences in 2- and 10-week mortality based on duration of ART.\ud \ud Conclusion\ud In this study, there were no significant differences in mortality at 2-and 10-weeks between ART- naive and experienced patients, and between ART-experienced patients according to duration on ART.

Published
2021

23. Cryptococcal Antigenemia in Advanced Human Immunodeficiency Virus Disease: Pathophysiology, Epidemiology, and Clinical Implications.

Author

Wake, Rachel M, Molloy, Síle F, Jarvis, Joseph N, Harrison, Thomas S, and Govender, Nelesh P

Subjects
*HIV infection epidemiology, *HIV infection complications, *ANTIBIOTICS, *CEREBROSPINAL fluid examination, *VIRAL antigens, *CRYPTOCOCCUS, *MEDICAL screening, *RISK assessment, *CRYPTOCOCCUS neoformans, *CD4 lymphocyte count, *MENINGITIS, *DIAGNOSTIC services, *DISEASE risk factors
Abstract

Cryptococcal antigen (CrAg) is detectable in blood prior to the onset of symptomatic cryptococcal meningitis (CM), a leading cause of death among people with advanced human immunodeficiency virus (HIV) disease globally. Highly sensitive assays can detect CrAg in blood, and screening people with HIV with low CD4 counts, followed by preemptive antifungal treatment, is recommended and widely implemented as part of a global strategy to prevent CM and end cryptococcal-related deaths. Cryptococcal antigenemia encompasses a spectrum of conditions from preclinical asymptomatic infection (cerebrospinal fluid [CSF] CrAg-negative) through subclinical (CSF CrAg-positive without overt meningism) to clinical symptomatic cryptococcal disease, usually manifesting as CM. In this review, we summarize current understanding of the pathophysiology, risk factors for, and clinical implications of cryptococcal antigenemia within this spectrum. We also provide an update on global prevalence, recommended screening and treatment strategies, and future considerations for improving outcomes among patients with cryptococcal antigenemia. [ABSTRACT FROM AUTHOR]

Published
2023
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25. Genomic variation across a clinical Cryptococcus population linked to disease outcome

Author

Sephton-Clark, Poppy, primary, Tenor, Jennifer L., additional, Toffaletti, Dena L., additional, Meyers, Nancy, additional, Giamberardino, Charles, additional, Molloy, Síle F., additional, Palmucci, Julia R., additional, Chan, Adrienne, additional, Chikaonda, Tarsizio, additional, Heyderman, Robert, additional, Hosseinipour, Mina, additional, Kalata, Newton, additional, Kanyama, Cecilia, additional, Kukacha, Christopher, additional, Lupiya, Duncan, additional, Mwandumba, Henry C., additional, Harrison, Thomas, additional, Bicanic, Tihana, additional, Perfect, John R., additional, and Cuomo, Christina A., additional

Published
2021
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26. Healthcare Costs and Life-years Gained From Treatments Within the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) Trial on Cryptococcal Meningitis: A Comparison of Antifungal Induction Strategies in Sub-Saharan Africa

Author

Chen, Tao, Mwenge, Lawrence, Lakhi, Shabir, Chanda, Duncan, Mwaba, Peter, Molloy, Síle F, Gheorghe, Adrian, Griffiths, Ulla K, Heyderman, Robert S, Kanyama, Cecilia, Kouanfack, Charles, Mfinanga, Sayoki, Chan, Adrienne K, Temfack, Elvis, Kivuyo, Sokoine, Hosseinipour, Mina C, Lortholary, Olivier, Loyse, Angela, Jaffar, Shabbar, Harrison, Thomas S, and Niessen, Louis W

Subjects
sub-Saharan Africa, Antifungal Agents, urogenital system, animal diseases, flucytosine, technology, industry, and agriculture, Health Care Costs, Meningitis, Cryptococcal, bacterial infections and mycoses, cryptococcal meningitis, antifungal induction treatments, parasitic diseases, Humans, Articles and Commentaries, cost-effectiveness, Africa South of the Sahara
Abstract

Background Mortality from cryptoccocal meningitis remains high. The ACTA trial demonstrated that, compared with 2 weeks of amphotericin B (AmB) plus flucystosine (5FC), 1 week of AmB and 5FC was associated with lower mortality and 2 weeks of oral flucanozole (FLU) plus 5FC was non-inferior. Here, we assess the cost-effectiveness of these different treatment courses. Methods Participants were randomized in a ratio of 2:1:1:1:1 to 2 weeks of oral 5FC and FLU, 1 week of AmB and FLU, 1 week of AmB and 5FC, 2 weeks of AmB and FLU, or 2 weeks of AmB and 5FC in Malawi, Zambia, Cameroon, and Tanzania. Data on individual resource use and health outcomes were collected. Cost-effectiveness was measured as incremental costs per life-year saved, and non-parametric bootstrapping was done. Results Total costs per patient were US $1442 for 2 weeks of oral FLU and 5FC, $1763 for 1 week of AmB and FLU, $1861 for 1 week of AmB and 5FC, $2125 for 2 weeks of AmB and FLU, and $2285 for 2 weeks of AmB and 5FC. Compared to 2 weeks of AmB and 5FC, 1 week of AmB and 5FC was less costly and more effective and 2 weeks of oral FLU and 5FC was less costly and as effective. The incremental cost-effectiveness ratio for 1 week of AmB and 5FC versus oral FLU and 5FC was US $208 (95% confidence interval $91–1210) per life-year saved. Clinical Trials Registration ISRCTN45035509. Conclusions Both 1 week of AmB and 5FC and 2 weeks of Oral FLU and 5FC are cost-effective treatments., Compared to 2 weeks of amphotericin B (AmB) and flucystosine (5FC), both 1 week of AmB/5FC and 2 weeks of oral fluconazole (FLU) and 5FC save costs; 1 week of AmB/5FC reduces mortality rates more and is somewhat more costly.

Published
2019

27. Fungal Burden and Raised Intracranial Pressure Are Independently Associated With Visual Loss in Human Immunodeficiency Virus-Associated Cryptococcal Meningitis

Author

Molloy, Síle F, primary, Ross, Brad, additional, Kanyama, Cecilia, additional, Mfinanga, Sayoki, additional, Lesikari, Sokoine, additional, Heyderman, Robert S, additional, Kalata, Newton, additional, Ellis, Jayne, additional, Kouanfack, Charles, additional, Chanda, Duncan, additional, Temfack, Elvis, additional, Lakhi, Shabir, additional, Moodley, Anand, additional, Chan, Adrienne K, additional, van Oosterhout, Joep J, additional, Mapoure, Yacouba, additional, Mwaba, Peter, additional, Lalloo, David G, additional, Wang, Duolao, additional, Lortholary, Olivier, additional, Jaffar, Shabbar, additional, Hosseinipour, Mina C, additional, Loyse, Angela, additional, Harrison, Thomas S, additional, and Bicanic, Tihana, additional

Published
2021
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28. Co-prevalent infections in adults with HIV-associated cryptococcal meningitis are associated with an increased risk of death: a nested analysis of the Advancing Cryptococcal meningitis Treatment for Africa (ACTA) cohort

Author

Ellis, Jayne, primary, Kalata, Newton, additional, Dziwani, Eltas, additional, Matope, Agnes, additional, Wang, Duolao, additional, Molloy, Síle F., additional, Harrison, Thomas S., additional, Lalloo, David G., additional, Sloan, Derek, additional, and Heyderman, Robert S., additional

Published
2021
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29. Diagnostic Accuracy of the Biosynex CryptoPS Cryptococcal Antigen Semiquantitative Lateral Flow Assay in Patients with Advanced HIV Disease

Author

Tenforde, Mark W., primary, Boyer-Chammard, Timothée, additional, Muthoga, Charles, additional, Tawe, Leabaneng, additional, Milton, Thandi, additional, Rulaganyang, Ikanyeng, additional, Lechiile, Kwana, additional, Rukasha, Ivy, additional, Leeme, Tshepo B., additional, Govender, Nelesh P., additional, Ngidi, Julia, additional, Mine, Madisa, additional, Molloy, Síle F., additional, Harrison, Thomas S., additional, Lortholary, Olivier, additional, and Jarvis, Joseph N., additional

Published
2020
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30. Evaluation of a Novel Semiquantitative Cryptococcal Antigen Lateral Flow Assay in Patients with Advanced HIV Disease

Author

Jarvis, Joseph N., primary, Tenforde, Mark W., additional, Lechiile, Kwana, additional, Milton, Thandi, additional, Boose, Amber, additional, Leeme, Tshepo B., additional, Tawe, Leabaneng, additional, Muthoga, Charles, additional, Rukasha, Ivy, additional, Mulenga, Fredah, additional, Rulaganyang, Ikanyeng, additional, Molefi, Mooketsi, additional, Molloy, Síle F., additional, Ngidi, Julia, additional, Harrison, Thomas S., additional, Govender, Nelesh P., additional, and Mine, Madisa, additional

Published
2020
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31. Dynamic ploidy changes drive fluconazole resistance in human cryptococcal meningitis

Author

Stone, Neil R.H., Rhodes, Johanna, Fisher, Matthew C., Mfinanga, Sayoki, Kivuyo, Sokoine, Rugemalila, Joan, Segal, Ella Shtifman, Needleman, Leor, Molloy, Síle F., Kwon-Chung, June, Harrison, Thomas S., Hope, William, Berman, Judith, and Bicanic, Tihana

Subjects
Male, HIGH-DOSE FLUCONAZOLE, PHARMACOKINETICS, MONOTHERAPY, Immunology, Meningitis, Cryptococcal, Research & Experimental Medicine, DISEASE, AIDS/HIV, Fungal infections, Drug Resistance, Fungal, wl_200, hemic and lymphatic diseases, Humans, Fluconazole, POPULATION, 11 Medical and Health Sciences, Infectious disease, Ploidies, Science & Technology, NEOFORMANS, Cryptococcus gattii, qv_252, FLUCYTOSINE, qw_51, Medicine, Research & Experimental, VORICONAZOLE, Cryptococcus neoformans, Female, TRIAL, Drug therapy, Clinical Medicine, qu_470, Life Sciences & Biomedicine, HETERORESISTANCE
Abstract

BACKGROUND\ud Cryptococcal meningitis (CM) causes an estimated 180,000 deaths annually, predominantly in sub-Saharan Africa, where most patients receive fluconazole (FLC) monotherapy. While relapse after FLC monotherapy with resistant strains is frequently observed, the mechanisms and impact of emergence of FLC resistance in human CM are poorly understood. Heteroresistance (HetR) - a resistant subpopulation within a susceptible strain - is a recently described phenomenon in Cryptococcus neoformans (Cn) and Cryptococcus gattii (Cg), the significance of which has not previously been studied in humans.\ud \ud METHODS\ud A cohort of 20 patients with HIV-associated CM in Tanzania was prospectively observed during therapy with either FLC monotherapy or in combination with flucytosine (5FC). Total and resistant subpopulations of Cryptococcus spp. were quantified directly from patient cerebrospinal fluid (CSF). Stored isolates underwent whole genome sequencing and phenotypic characterization.\ud \ud RESULTS\ud Heteroresistance was detectable in Cryptococcus spp. in the CSF of all patients at baseline (i.e., prior to initiation of therapy). During FLC monotherapy, the proportion of resistant colonies in the CSF increased during the first 2 weeks of treatment. In contrast, no resistant subpopulation was detectable in CSF by day 14 in those receiving a combination of FLC and 5FC. Genomic analysis revealed high rates of aneuploidy in heteroresistant colonies as well as in relapse isolates, with chromosome 1 (Chr1) disomy predominating. This is apparently due to the presence on Chr1 of ERG11, which is the FLC drug target, and AFR1, which encodes a drug efflux pump. In vitro efflux levels positively correlated with the level of heteroresistance.\ud \ud CONCLUSION\ud Our findings demonstrate for what we believe is the first time the presence and emergence of aneuploidy-driven FLC heteroresistance in human CM, association of efflux levels with heteroresistance, and the successful suppression of heteroresistance with 5FC/FLC combination therapy.\ud \ud FUNDING\ud This work was supported by the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377/Z/11/Z and the Daniel Turnberg Travel Fellowship.

Published
2019

32. Plasma cytokines, chemokines and cellular immune responses in pre-school Nigerian children infected with Plasmodium falciparum

Author

Noone Cariosa, Parkinson Michael, Dowling David J, Aldridge Allison, Kirwan Patrick, Molloy Síle F, Asaolu Samuel O, Holland Celia, and O’Neill Sandra M

Subjects
Cytokines, Chemokines, Cellular responses, Plasmodium falciparum, Children, Nigeria, Ascaris lumbricoides, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Malaria is a major cause of morbidity and mortality worldwide with over one million deaths annually, particularly in children under five years. This study was the first to examine plasma cytokines, chemokines and cellular immune responses in pre-school Nigerian children infected with Plasmodium falciparum from four semi-urban villages near Ile-Ife, Osun State, Nigeria. Methods Blood was obtained from 231 children (aged 39–73 months) who were classified according to mean P. falciparum density per μl of blood (uninfected (n = 89), low density (10,000, n = 22)). IL-12p70, IL-10, Nitric oxide, IFN-γ, TNF, IL-17, IL-4 and TGF-β, C-C chemokine RANTES, MMP-8 and TIMP-1 were measured in plasma. Peripheral blood mononuclear cells were obtained and examined markers of innate immune cells (CD14, CD36, CD56, CD54, CD11c AND HLA-DR). T-cell sub-populations (CD4, CD3 and γδTCR) were intracellularly stained for IL-10, IFN-γ and TNF following polyclonal stimulation or stimulated with malaria parasites. Ascaris lumbricoides was endemic in these villages and all data were analysed taking into account the potential impact of bystander helminth infection. All data were analysed using SPSS 15 for windows and in all tests, p Results The level of P. falciparum parasitaemia was positively associated with plasma IL-10 and negatively associated with IL-12p70. The percentage of monocytes was significantly decreased in malaria-infected individuals while malaria parasitaemia was positively associated with increasing percentages of CD54+, CD11c+ and CD56+ cell populations. No association was observed in cytokine expression in mitogen-activated T-cell populations between groups and no malaria specific immune responses were detected. Although A. lumbricoides is endemic in these villages, an analysis of the data showed no impact of this helminth infection on P. falciparum parasitaemia or on immune responses associated with P. falciparum infection. Conclusions These findings indicate that Nigerian children infected with P. falciparum exhibit immune responses associated with active malaria infection and these responses were positively associated with increased P. falciparum parasitaemia.

Published
2013
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33. Ascaris co-infection does not alter malaria-induced anaemia in a cohort of Nigerian preschool children

Author

Abanyie Francisca A, McCracken Courtney, Kirwan Patrick, Molloy Síle F, Asaolu Samuel O, Holland Celia V, Gutman Julie, and Lamb Tracey J

Subjects
Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Co-infection with malaria and intestinal parasites such as Ascaris lumbricoides is common. Malaria parasites induce a pro-inflammatory immune response that contributes to the pathogenic sequelae, such as malarial anaemia, that occur in malaria infection. Ascaris is known to create an anti-inflammatory immune environment which could, in theory, counteract the anti-malarial inflammatory immune response, minimizing the severity of malarial anaemia. This study examined whether Ascaris co-infection can minimize the severity of malarial anaemia. Methods Data from a randomized controlled trial on the effect of antihelminthic treatment in Nigerian preschool-aged (6–59 months) children conducted in 2006–2007 were analysed to examine the effect of malaria and Ascaris co-infection on anaemia severity. Children were enrolled and tested for malaria, helminths and anaemia at baseline, four, and eight months. Six hundred and ninety subjects were analysed in this study. Generalized linear mixed models were used to assess the relationship between infection status and Ascaris and Plasmodium parasite intensity on severity of anaemia, defined as a haemoglobin less than 11 g/dL. Results Malaria prevalence ranged from 35-78% over the course of this study. Of the malaria-infected children, 55% were co-infected with Ascaris at baseline, 60% were co-infected four months later and 48% were co-infected eight months later, underlining the persistent prevalence of malaria-nematode co-infections in this population. Over the course of the study the percentage of anaemic subjects in the population ranged between 84% at baseline and 77% at the eight-month time point. The odds of being anaemic were four to five times higher in children infected with malaria compared to those without malaria. Ascaris infection alone did not increase the odds of being anaemic, indicating that malaria was the main cause of anaemia in this population. There was no significant difference in the severity of anaemia between children singly infected with malaria and co-infected with malaria and Ascaris. Conclusion In this cohort of Nigerian preschool children, malaria infection was the major contributor to anaemia status. Ascaris co-infection neither exacerbated nor ameliorated the severity of malarial anaemia.

Published
2013
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34. Accepted: Clinical Infectious Diseases. Health care costs and life years gained from treatments within the ACTA trial on cryptococcal meningitis: a comparison of antifungal induction strategies in SSA

Author

Chen, Tao, Mwenge, Lawrence, Lakhi, Shabir, Chanda, Duncan, Mwaba, Peter, Molloy, Síle F, Gheorghe, Adrian, Griffiths, Ulla K, Heyderman, Robert S, Kanyama, Cecilia, Kouanfack, Charles, Sayoki Mfinanga, Chan, Adrienne K, Temfack, Elvis, Sokoine Kivuyo, Hosseinipour, Mina C, Lortholary, Olivier, Loyse, Angela, Shabbar Jaffar, Harrison, Thomas S, and Niessen, Louis

Published
2018
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35. One-year Mortality Outcomes From the Advancing Cryptococcal Meningitis Treatment for Africa Trial of Cryptococcal Meningitis Treatment in Malawi

Author

Kanyama, Cecilia, primary, Molloy, Síle F, primary, Chan, Adrienne K, primary, Lupiya, Duncan, primary, Chawinga, Chimwemwe, primary, Adams, Jack, primary, Bright, Philip, primary, Lalloo, David G, primary, Heyderman, Robert S, primary, Lortholary, Olivier, primary, Jaffar, Shabbar, primary, Loyse, Angela, primary, van Oosterhout, Joep J, primary, Hosseinipour, Mina C, primary, and Harrison, Thomas S, primary

Published
2019
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36. Addition of Flucytosine to Fluconazole for the Treatment of Cryptococcal Meningitis in Africa: A Multicountry Cost-effectiveness Analysis

Author

Shiri, Tinevimbo, primary, Loyse, Angela, additional, Mwenge, Lawrence, additional, Chen, Tao, additional, Lakhi, Shabir, additional, Chanda, Duncan, additional, Mwaba, Peter, additional, Molloy, Síle F, additional, Heyderman, Robert S, additional, Kanyama, Cecilia, additional, Hosseinipour, Mina C, additional, Kouanfack, Charles, additional, Temfack, Elvis, additional, Mfinanga, Sayoki, additional, Kivuyo, Sokoine, additional, Chan, Adrienne K, additional, Jarvis, Joseph N, additional, Lortholary, Olivier, additional, Jaffar, Shabbar, additional, Niessen, Louis W, additional, and Harrison, Thomas S, additional

Published
2019
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37. Patterns of soil-transmitted helminth infection and impact of four-monthly albendazole treatments in preschool children from semi-urban communities in Nigeria: a double-blind placebo-controlled randomised trial

Author

Jackson Andrew L, Abiona Titilayo C, Molloy Síle F, Asaolu Samuel O, Kirwan Patrick, and Holland Celia V

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Children aged between one and five years are particularly vulnerable to disease caused by soil-transmitted helminths (STH). Periodic deworming has been shown to improve growth, micronutrient status (iron and vitamin A), and motor and language development in preschool children and justifies the inclusion of this age group in deworming programmes. Our objectives were to describe the prevalence and intensity of STH infection and to investigate the effectiveness of repeated four-monthly albendazole treatments on STH infection in children aged one to four years. Methods The study was carried out in four semi-urban villages situated near Ile-Ife, Osun State, Nigeria. The study was a double-blind placebo-controlled randomised trial. Children aged one to four years were randomly assigned to receive either albendazole or placebo every four months for 12 months with a follow-up at 14 months. Results The results presented here revealed that 50% of the preschool children in these semi-urban communities were infected by one or more helminths, the most prevalent STH being Ascaris lumbricoides (47.6%). Our study demonstrated that repeated four-monthly anthelminthic treatments with albendazole were successful in reducing prevalence and intensity of A. lumbricoides infections. At the end of the follow-up period, 12% and 43% of the children were infected with A. lumbricoides and mean epg was 117 (S.E. 50) and 1740 (S.E. 291) in the treatment and placebo groups respectively compared to 45% and 45% of the children being infected with Ascaris and mean epg being 1095 (S.E. 237) and 1126 (S.E. 182) in the treatment and placebo group respectively at baseline. Conclusion Results from this study show that the moderate prevalence and low intensity of STH infection in these preschool children necessitates systematic treatment of the children in child health programmes. Trial Registration Current controlled trials ISRCTN44215995.

Published
2009
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38. One-year Mortality Outcomes From the Advancing Cryptococcal Meningitis Treatment for Africa Trial of Cryptococcal Meningitis Treatment in Malawi.

Author

Kanyama, Cecilia, Molloy, Síle F, Chan, Adrienne K, Lupiya, Duncan, Chawinga, Chimwemwe, Adams, Jack, Bright, Philip, Lalloo, David G, Heyderman, Robert S, Lortholary, Olivier, Jaffar, Shabbar, Loyse, Angela, Oosterhout, Joep J van, Hosseinipour, Mina C, and Harrison, Thomas S

Subjects
*AMPHOTERICIN B, *COMBINATION drug therapy, *CONFIDENCE intervals, *CRYPTOCOCCUS neoformans, *HETEROCYCLIC compounds, *LONGITUDINAL method, *MENINGITIS, *RISK assessment, *RANDOMIZED controlled trials, *TREATMENT effectiveness, *DESCRIPTIVE statistics
Abstract

In Malawi, 236 participants from the Advancing Cryptococcal Meningitis Treatment for Africa trial were followed for 12 months. The trial outcomes reported at 10 weeks were sustained to 1 year. One-week amphotericin B plus flucytosine was associated with the lowest 1 year mortality (27.5% [95% confidence interval, 16.3 to 44.1]). [ABSTRACT FROM AUTHOR]

Published
2020
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39. Addition of Flucytosine to Fluconazole for the Treatment of Cryptococcal Meningitis in Africa: A Multicountry Cost-effectiveness Analysis.

Author

Shiri, Tinevimbo, Loyse, Angela, Mwenge, Lawrence, Chen, Tao, Lakhi, Shabir, Chanda, Duncan, Mwaba, Peter, Molloy, Síle F, Heyderman, Robert S, Kanyama, Cecilia, Hosseinipour, Mina C, Kouanfack, Charles, Temfack, Elvis, Mfinanga, Sayoki, Kivuyo, Sokoine, Chan, Adrienne K, Jarvis, Joseph N, Lortholary, Olivier, Jaffar, Shabbar, and Niessen, Louis W

Subjects
ANTIFUNGAL agents, COMBINATION drug therapy, CONFIDENCE intervals, COST control, COST effectiveness, CRYPTOCOCCUS neoformans, MEDICAL care costs, MENINGITIS, DESCRIPTIVE statistics, FLUCONAZOLE
Abstract

Background Mortality from cryptococcal meningitis remains very high in Africa. In the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) trial, 2 weeks of fluconazole (FLU) plus flucytosine (5FC) was as effective and less costly than 2 weeks of amphotericin-based regimens. However, many African settings treat with FLU monotherapy, and the cost-effectiveness of adding 5FC to FLU is uncertain. Methods The effectiveness and costs of FLU+5FC were taken from ACTA, which included a costing analysis at the Zambian site. The effectiveness of FLU was derived from cohorts of consecutively enrolled patients, managed in respects other than drug therapy, as were participants in ACTA. FLU costs were derived from costs of FLU+5FC in ACTA, by subtracting 5FC drug and monitoring costs. The cost-effectiveness of FLU+5FC vs FLU alone was measured as the incremental cost-effectiveness ratio (ICER). A probabilistic sensitivity analysis assessed uncertainties and a bivariate deterministic sensitivity analysis examined the impact of varying mortality and 5FC drug costs on the ICER. Results The mean costs per patient were US $847 (95% confidence interval [CI] $776–927) for FLU+5FC, and US $628 (95% CI $557–709) for FLU. The 10-week mortality rate was 35.1% (95% CI 28.9–41.7%) with FLU+5FC and 53.8% (95% CI 43.1–64.1%) with FLU. At the current 5FC price of US $1.30 per 500 mg tablet, the ICER of 5FC+FLU versus FLU alone was US $65 (95% CI $28–208) per life-year saved. Reducing the 5FC cost to between US $0.80 and US $0.40 per 500 mg resulted in an ICER between US $44 and US $28 per life-year saved. Conclusions The addition of 5FC to FLU is cost-effective for cryptococcal meningitis treatment in Africa and, if made available widely, could substantially reduce mortality rates among human immunodeficiency virus–infected persons in Africa. [ABSTRACT FROM AUTHOR]

Published
2020
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40. Short-course High-dose Liposomal Amphotericin B for Human Immunodeficiency Virus–associated Cryptococcal Meningitis: A Phase 2 Randomized Controlled Trial

Author

Jarvis, Joseph N, primary, Leeme, Tshepo B, additional, Molefi, Mooketsi, additional, Chofle, Awilly A, additional, Bidwell, Gabriella, additional, Tsholo, Katlego, additional, Tlhako, Nametso, additional, Mawoko, Norah, additional, Patel, Raju K K, additional, Tenforde, Mark W, additional, Muthoga, Charles, additional, Bisson, Gregory P, additional, Kidola, Jeremiah, additional, Changalucha, John, additional, Lawrence, David, additional, Jaffar, Shabbar, additional, Hope, William, additional, Molloy, Síle F, additional, and Harrison, Thomas S, additional

Published
2018
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41. Cryptococcal Antigen Screening in Asymptomatic HIV-Infected Antiretroviral Naïve Patients in Cameroon and Evaluation of the New Semi-Quantitative Biosynex CryptoPS Test

Author

Temfack, Elvis, primary, Kouanfack, Charles, additional, Mossiang, Leonella, additional, Loyse, Angela, additional, Fonkoua, Marie C., additional, Molloy, Síle F., additional, Koulla-Shiro, Sinata, additional, Delaporte, Eric, additional, Dromer, Françoise, additional, Harrison, Thomas, additional, and Lortholary, Olivier, additional

Published
2018
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43. Cryptococcal meningitis: A neglected NTD?

Author

Molloy, Síle F., primary, Chiller, Tom, additional, Greene, Gregory S., additional, Burry, Jessica, additional, Govender, Nelesh P., additional, Kanyama, Cecilia, additional, Mfinanga, Sayoki, additional, Lesikari, Sokoine, additional, Mapoure, Yacouba N., additional, Kouanfack, Charles, additional, Sini, Victor, additional, Temfack, Elvis, additional, Boulware, David R., additional, Dromer, Francoise, additional, Denning, David W., additional, Day, Jeremy, additional, Stone, Neil R. H., additional, Bicanic, Tihana, additional, Jarvis, Joseph N., additional, Lortholary, Olivier, additional, Harrison, Thomas S., additional, Jaffar, Shabbar, additional, and Loyse, Angela, additional

Published
2017
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44. Short-course High-dose Liposomal Amphotericin B for Human Immunodeficiency Virus–associated Cryptococcal Meningitis: A Phase 2 Randomized Controlled Trial.

Author

Jarvis, Joseph N, Leeme, Tshepo B, Molefi, Mooketsi, Chofle, Awilly A, Bidwell, Gabriella, Tsholo, Katlego, Tlhako, Nametso, Mawoko, Norah, Patel, Raju K K, Tenforde, Mark W, Muthoga, Charles, Bisson, Gregory P, Kidola, Jeremiah, Changalucha, John, Lawrence, David, Jaffar, Shabbar, Hope, William, Molloy, Síle F, and Harrison, Thomas S

Subjects
MENINGITIS diagnosis, CRYPTOCOCCUS neoformans, AMPHOTERICIN B, CONFIDENCE intervals, HIV infections, RANDOMIZED controlled trials, FLUCONAZOLE, PHARMACODYNAMICS, DIAGNOSIS
Abstract

Background We performed a phase 2 noninferiority trial examining the early fungicidal activity (EFA) of 3 short-course, high-dose liposomal amphotericin B (L-AmB) regimens for cryptococcal meningitis (CM) in Tanzania and Botswana. Methods Human immunodeficiency virus (HIV)-infected adults with CM were randomized to (i) L-AmB 10 mg/kg on day 1 (single dose); (ii) L-AmB 10 mg/kg on day 1 and 5 mg/kg on day 3 (2 doses); (iii) L-AmB 10 mg/kg on day 1 and 5 mg/kg on days 3 and 7 (3 doses); or (iv) L-AmB 3 mg/kg/day for 14 days (control). All patients also received oral fluconazole 1200 mg/day for 14 days. Primary endpoint was mean rate of clearance of cerebrospinal fluid cryptococcal infection (EFA). Noninferiority was defined as an upper limit of the 2-sided 95% confidence interval (CI) of difference in EFA between intervention and control <0.2 log10 colony-forming units (CFU)/mL/day. Results Eighty participants were enrolled. EFA for daily L-AmB was –0.41 log10 CFU/mL/day (standard deviation, 0.11; n = 17). Difference in mean EFA from control was –0.11 (95% CI, –.29 to.07) log10 CFU/mL/day faster with single dose (n = 16); –0.05 (95% CI, –.20 to.10) log10 CFU/mL/day faster with 2 doses (n = 18); and –0.13 (95% CI, –.35 to.09) log10 CFU/mL/day faster with 3 doses (n = 18). EFA in all short-course arms was noninferior to control. Ten-week mortality was 29% (n = 23) with no statistical difference between arms. All arms were well tolerated. Conclusions Single-dose 10 mg/kg L-AmB was well tolerated and led to noninferior EFA compared to 14 days of 3 mg/kg/day L-AmB in HIV-associated CM. Induction based on a single 10 mg/kg L-AmB dose is being taken forward to a phase 3 clinical endpoint trial. Clinical Trials Registration ISRCTN 10248064. [ABSTRACT FROM AUTHOR]

Published
2019
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47. AMBITION-cm: intermittent high dose AmBisome on a high dose fluconazole backbone for cryptococcal meningitis induction therapy in sub-Saharan Africa: study protocol for a randomized controlled trial

Author

Molefi, Mooketsi, primary, Chofle, Awilly A., additional, Molloy, Síle F., additional, Kalluvya, Samuel, additional, Changalucha, John M., additional, Cainelli, Francesca, additional, Leeme, Tshepo, additional, Lekwape, Nametso, additional, Goldberg, Drew W., additional, Haverkamp, Miriam, additional, Bisson, Gregory P., additional, Perfect, John R., additional, Letang, Emili, additional, Fenner, Lukas, additional, Meintjes, Graeme, additional, Burton, Rosie, additional, Makadzange, Tariro, additional, Ndhlovu, Chiratidzo E., additional, Hope, William, additional, Harrison, Thomas S., additional, and Jarvis, Joseph N., additional

Published
2015
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48. Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy

Author

Williamson, Peter R., Jarvis, Joseph N., Panackal, Anil A., Fisher, Matthew C., Molloy, Síle F., Loyse, Angela, and Harrison, Thomas S.

Abstract

HIV-associated cryptococcal meningitis is by far the most common cause of adult meningitis in many areas of the world that have high HIV seroprevalence. In most areas in Sub-Saharan Africa, the incidence of cryptococcal meningitis is not decreasing despite availability of antiretroviral therapy, because of issues of adherence and retention in HIV care. In addition, cryptococcal meningitis in HIV-seronegative individuals is a substantial problem: the risk of cryptococcal infection is increased in transplant recipients and other individuals with defects in cell-mediated immunity, and cryptococcosis is also reported in the apparently immunocompetent. Despite therapy, mortality rates in these groups are high. Over the past 5 years, advances have been made in rapid point-of-care diagnosis and early detection of cryptococcal antigen in the blood. These advances have enabled development of screening and pre-emptive treatment strategies aimed at preventing the development of clinical infection in patients with late-stage HIV infection. Progress in optimizing antifungal combinations has been aided by evaluation of the clearance rate of infection by using serial quantitative cultures of cerebrospinal fluid (CSF). Measurement and management of raised CSF pressure, a common complication, is a vital component of care. In addition, we now better understand protective immune responses in HIV-associated cases, immunogenetic predisposition to infection, and the role of immune-mediated pathology in patients with non-HIV associated infection and in the context of HIV-associated immune reconstitution reactions.

Published
2017
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