Search

Your search keyword '"Musicha, P"' showing total 43 results
Start Over Author "Musicha, P"
43 results on '"Musicha, P"'

3. Genomic insights into the 2022–2023Vibrio cholerae outbreak in Malawi

Author

Chaguza, Chrispin, Chibwe, Innocent, Chaima, David, Musicha, Patrick, Ndeketa, Latif, Kasambara, Watipaso, Mhango, Chimwemwe, Mseka, Upendo L., Bitilinyu-Bangoh, Joseph, Mvula, Bernard, Kipandula, Wakisa, Bonongwe, Patrick, Munthali, Richard J., Ngwira, Selemani, Mwendera, Chikondi A., Kalizang’oma, Akuzike, Jambo, Kondwani C., Kambalame, Dzinkambani, Kamng’ona, Arox W., Steele, A. Duncan, Chauma-Mwale, Annie, Hungerford, Daniel, Kagoli, Matthew, Nyaga, Martin M., Dube, Queen, French, Neil, Msefula, Chisomo L., Cunliffe, Nigel A., and Jere, Khuzwayo C.

Published
2024
Full Text
View/download PDF

4. Longitudinal analysis within one hospital in sub-Saharan Africa over 20 years reveals repeated replacements of dominant clones of Klebsiella pneumoniae and stresses the importance to include temporal patterns for vaccine design considerations

Author

Heinz, Eva, Pearse, Oliver, Zuza, Allan, Bilima, Sithembile, Msefula, Chisomo, Musicha, Patrick, Siyabu, Patriciah, Tewesa, Edith, Graf, Fabrice E., Lester, Rebecca, Lissauer, Samantha, Cornick, Jennifer, Lewis, Joseph M., Kawaza, Kondwani, Thomson, Nicholas R., and Feasey, Nicholas A.

Published
2024
Full Text
View/download PDF

10. Polygenic basis and biomedical consequences of telomere length variation

Author

Codd, Veryan, Wang, Qingning, Allara, Elias, Musicha, Crispin, Kaptoge, Stephen, Stoma, Svetlana, Jiang, Tao, Hamby, Stephen E., Braund, Peter S., Bountziouka, Vasiliki, Budgeon, Charley A., Denniff, Matthew, Swinfield, Chloe, Papakonstantinou, Manolo, Sheth, Shilpi, Nanus, Dominika E., Warner, Sophie C., Wang, Minxian, Khera, Amit V., Eales, James, Ouwehand, Willem H., Thompson, John R., Di Angelantonio, Emanuele, Wood, Angela M., Butterworth, Adam S., Danesh, John N., Nelson, Christopher P., and Samani, Nilesh J.

Published
2021
Full Text
View/download PDF

11. Epidemiological and genomic landscape of antimicrobial resistance in Malawi

Author

Musicha, P., Everett, D. B., Msefula, C. L., and Feasey, N. A.

Subjects
615.7
Abstract

Antimicrobial resistance (AMR) is a global public health problem, which presents a huge threat to the treatment of all forms of bacterial infections. A wide range of bacterial pathogens across the globe are increasingly developing resistance to multiple classes of antimicrobial agents rendering the agents concerned ineffective for the treatment of infections. Bloodstream infection (BSI) and other bacterial infections in sub-Saharan Africa (SSA) and Malawi in particular, are a common cause of morbidity and mortality. Few facilities in SSA however, are able to conduct long-term surveillance and as such the full burden of drug resistant infection (DRI) remain largely unknown across the region. In this thesis, blood cultures routinely taken from adult and paediatric medical patients admitted to Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi between 1998 and 2016 were analysed to describe trends in BSI and AMR. The analysis revealed a significant decline of BSI in all major pathogens except S. Typhi. However, the majority of isolates were resistant to the Malawian first-line antimicrobial agents (ampicillin, cotrimoxazole and chloramphenicol). Resistance to all the first line antimicrobial agents was more common in Gram-negative pathogens than Gram-positive pathogens. Non-Salmonellae Enterobacteriaceae that produced extended spectrum beta-lactamase (ESBL) and were fluoroquinolone-resistant were detected, and the proportions of these isolates rose significantly during the surveillance. In contrast, a majority of common Gram-positive pathogens remain susceptible to either penicillin or chloramphenicol. Methicillin resistant S. aureus was first reported in 1998 but became regularly detected in the later years of the surveillance. The analysis of blood culture isolates identified E. coli as one of the common causes of BSI in Blantyre, and the proportion of these isolates that were ESBL producers increased over time. Globally, efforts to treat E. coli infections are increasingly being compromised by the rapid, global spread of ESBL-producing E. coli. In this thesis, a whole genome sequencing (WGS) study was carried out to investigate the genetic population structure and molecular determinants of AMR in E. coli isolates from Malawi. Whole genomes of clinical E. coli isolates from patients admitted to QECH were sequenced and analysed using phylogenetic methods and comparative genomics. It was revealed that the E. coli population in Malawi is highly diverse with isolates belonging to five phylogroups, corresponding to five isolate sequence clusters (SCs) that contained over forty sequence types (STs). A unique sub-lineage of ST131 was identified that was distinct from previously defined sub-lineages of this globally disseminated ST. The most common ESBL gene was blaCT X-M-15. Unlike in other settings where presence of the blaCT X-M-15 gene was strongly linked to ST131, here the gene was not lineage-specific suggesting a distinct genomic landscape of ESBL-producing E. coli in Malawi. This thesis also identified Klebsiella spp. isolates as a common cause of BSI in Blantyre, and an increasing proportion of ESBL-producing and fluoroquinolone resistant isolates were identified. The molecular mechanisms and clones of K. pneumoniae associated with ESBL production and fluoroquinolone resistance were yet to be explored in Malawi. Here, a number of K. pneumoniae isolates were selected for WGS, and placed in a global context by comparison with previously sequenced K. pneumoniae isolates from multiple locations outside SSA, in order to identify the molecular determinants of AMR and determine their relationship with K. pneumoniae population structure. Genomic analysis revealed three main lineages of K. pneumoniae, which corresponded to the previously defined KpI, KpII and KpIII lineages. All three lineages exhibited high genetic diversity. Further phylogenetic analysis revealed a sub-lineage of KpI to be a major cause of CA infections in Malawi. The sub-lineage included the clonally related ST14 and ST15 of K. pneumoniae which cause hospital acquired infection in multiple settings across the globe, A large pool of AMR genes, was identified in the genomes of the Malawian isolates, including multiple ESBL and qnr genes. Plasmid-encoded CTX-M-15 was the most common type of ESBL that was identified. In common with E. coli from Malawi, AMR was not restricted to a particular clade of K. pneumoniae. These findings suggest that dissemination of AMR in the K. pneumoniae population in Malawi was either due to a combination of horizontal gene transfer and clonal expansion, or horizontal gene transfer alone. In conclusion, the thesis has shown that ESBL production and fluoroquinolone resistance is rapidly spreading in Malawi across multiple E. coli and K. pneumoniae lineages that are causing increasing levels of infection. As cephalosporins and fluoroquinolones remain the last resort antimicrobial agents in this setting, urgent action is needed to curb the spread of Gram-negative AMR pathogens.

Published
2017
Full Text
View/download PDF

14. Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050

Author

Naghavi, M, Vollset, SE, Ikuta, KS, Swetschinski, LR, Gray, AP, Wool, EE, Robles Aguilar, G, Mestrovic, T, Smith, G, Han, C, Hsu, RL, Azzam, AY, Babaei, M, Babin, F-X, Badar, M, Baig, AA, Bajcetic, M, Baker, S, Bardhan, M, Barqawi, HJ, Basharat, Z, Chalek, J, Basiru, A, Bastard, M, Basu, S, Bayleyegn, NS, Belete, MA, Bello, OO, Beloukas, A, Berkley, JA, Bhagavathula, AS, Bhaskar, S, Araki, DT, Bhuyan, SS, Bielicki, JA, Briko, NI, Brown, CS, Browne, AJ, Buonsenso, D, Bustanji, Y, Carvalheiro, CG, Castañeda-Orjuela, CA, Cenderadewi, M, Chung, E, Chadwick, J, Chakraborty, S, Chandika, RM, Chandy, S, Chansamouth, V, Chattu, VK, Chaudhary, AA, Ching, PR, Chopra, H, Chowdhury, FR, Raggi, C, Chu, D-T, Chutiyami, M, Cruz-Martins, N, da Silva, AG, Dadras, O, Dai, X, Darcho, SD, Das, S, De la Hoz, FP, Dekker, DM, Gershberg Hayoon, A, Dhama, K, Diaz, D, Dickson, BFR, Djorie, SG, Dodangeh, M, Dohare, S, Dokova, KG, Doshi, OP, Dowou, RK, Dsouza, HL, Davis Weaver, N, Dunachie, SJ, Dziedzic, AM, Eckmanns, T, Ed-Dra, A, Eftekharimehrabad, A, Ekundayo, TC, El Sayed, I, Elhadi, M, El-Huneidi, W, Elias, C, Lindstedt, PA, Ellis, SJ, Elsheikh, R, Elsohaby, I, Eltaha, C, Eshrati, B, Eslami, M, Eyre, DW, Fadaka, AO, Fagbamigbe, AF, Fahim, A, Smith, AE, Fakhri-Demeshghieh, A, Fasina, FO, Fasina, MM, Fatehizadeh, A, Feasey, NA, Feizkhah, A, Fekadu, G, Fischer, F, Fitriana, I, Forrest, KM, Altay, U, Fortuna Rodrigues, C, Fuller, JE, Gadanya, MA, Gajdács, M, Gandhi, AP, Garcia-Gallo, EE, Garrett, DO, Gautam, RK, Gebregergis, MW, Gebrehiwot, M, Bhattacharjee, NV, Gebremeskel, TG, Geffers, C, Georgalis, L, Ghazy, RM, Golechha, M, Golinelli, D, Gordon, M, Gulati, S, Gupta, RD, Gupta, S, Giannakis, K, Gupta, VK, Habteyohannes, AD, Haller, S, Harapan, H, Harrison, ML, Hasaballah, AI, Hasan, I, Hasan, RS, Hasani, H, Haselbeck, AH, Fell, F, Hasnain, MS, Hassan, II, Hassan, S, Hassan Zadeh Tabatabaei, MS, Hayat, K, He, J, Hegazi, OE, Heidari, M, Hezam, K, Holla, R, McManigal, B, Holm, M, Hopkins, H, Hossain, MM, Hosseinzadeh, M, Hostiuc, S, Hussein, NR, Huy, LD, Ibáñez-Prada, ED, Ikiroma, A, Ilic, IM, Ekapirat, N, Islam, SMS, Ismail, F, Ismail, NE, Iwu, CD, Iwu-Jaja, CJ, Jafarzadeh, A, Jaiteh, F, Jalilzadeh Yengejeh, R, Jamora, RDG, Javidnia, J, Mendes, JA, Jawaid, T, Jenney, AWJ, Jeon, HJ, Jokar, M, Jomehzadeh, N, Joo, T, Joseph, N, Kamal, Z, Kanmodi, KK, Kantar, RS, Runghien, T, Kapisi, JA, Karaye, IM, Khader, YS, Khajuria, H, Khalid, N, Khamesipour, F, Khan, A, Khan, MJ, Khan, MT, Khanal, V, Srimokla, O, Khidri, FF, Khubchandani, J, Khusuwan, S, Kim, MS, Kisa, A, Korshunov, VA, Krapp, F, Krumkamp, R, Kuddus, M, Kulimbet, M, Abdelkader, A, Kumar, D, Kumaran, EAP, Kuttikkattu, A, Kyu, HH, Landires, I, Lawal, BK, Le, TTT, Lederer, IM, Lee, M, Lee, SW, Abd-Elsalam, S, Lepape, A, Lerango, TL, Ligade, VS, Lim, C, Lim, SS, Limenh, LW, Liu, C, Liu, X, Loftus, MJ, Aboagye, RG, M Amin, HI, Maass, KL, Maharaj, SB, Mahmoud, MA, Maikanti-Charalampous, P, Makram, OM, Malhotra, K, Malik, AA, Mandilara, GD, Marks, F, Abolhassani, H, Martinez-Guerra, BA, Martorell, M, Masoumi-Asl, H, Mathioudakis, AG, May, J, McHugh, TA, Meiring, J, Meles, HN, Melese, A, Melese, EB, Abualruz, H, Minervini, G, Mohamed, NS, Mohammed, S, Mohan, S, Mokdad, AH, Monasta, L, Moodi Ghalibaf, A, Moore, CE, Moradi, Y, Mossialos, E, Abubakar, U, Mougin, V, Mukoro, GD, Mulita, F, Muller-Pebody, B, Murillo-Zamora, E, Musa, S, Musicha, P, Musila, LA, Muthupandian, S, Nagarajan, AJ, Abukhadijah, HJ, Naghavi, P, Nainu, F, Nair, TS, Najmuldeen, HHR, Natto, ZS, Nauman, J, Nayak, BP, Nchanji, GT, Ndishimye, P, Negoi, I, Aburuz, S, Negoi, RI, Nejadghaderi, SA, Nguyen, QP, Noman, EA, Nwakanma, DC, O'Brien, S, Ochoa, TJ, Odetokun, IA, Ogundijo, OA, Ojo-Akosile, TR, Abu-Zaid, A, Okeke, SR, Okonji, OC, Olagunju, AT, Olivas-Martinez, A, Olorukooba, AA, Olwoch, P, Onyedibe, KI, Ortiz-Brizuela, E, Osuolale, O, Ounchanum, P, Achalapong, S, Oyeyemi, OT, P A, MP, Paredes, JL, Parikh, RR, Patel, J, Patil, S, Pawar, S, Peleg, AY, Peprah, P, Perdigão, J, Addo, IY, Perrone, C, Petcu, I-R, Phommasone, K, Piracha, ZZ, Poddighe, D, Pollard, AJ, Poluru, R, Ponce-De-Leon, A, Puvvula, J, Qamar, FN, Adekanmbi, V, Qasim, NH, Rafai, CD, Raghav, P, Rahbarnia, L, Rahim, F, Rahimi-Movaghar, V, Rahman, M, Rahman, MA, Ramadan, H, Ramasamy, SK, Adeyeoluwa, TE, Ramesh, PS, Ramteke, PW, Rana, RK, Rani, U, Rashidi, M-M, Rathish, D, Rattanavong, S, Rawaf, S, Redwan, EMM, Reyes, LF, Adnani, QES, Roberts, T, Robotham, JV, Rosenthal, VD, Ross, AG, Roy, N, Rudd, KE, Sabet, CJ, Saddik, BA, Saeb, MR, Saeed, U, Adzigbli, LA, Saeedi Moghaddam, S, Saengchan, W, Safaei, M, Saghazadeh, A, Saheb Sharif-Askari, N, Sahebkar, A, Sahoo, SS, Sahu, M, Saki, M, Salam, N, Afzal, MS, Saleem, Z, Saleh, MA, Samodra, YL, Samy, AM, Saravanan, A, Satpathy, M, Schumacher, AE, Sedighi, M, Seekaew, S, Shafie, M, Afzal, S, Shah, PA, Shahid, S, Shahwan, MJ, Shakoor, S, Shalev, N, Shamim, MA, Shamshirgaran, MA, Shamsi, A, Sharifan, A, Shastry, RP, Agodi, A, Shetty, M, Shittu, A, Shrestha, S, Siddig, EE, Sideroglou, T, Sifuentes-Osornio, J, Silva, LMLR, Simões, EAF, Simpson, AJH, Singh, A, Ahlstrom, AJ, Singh, S, Sinto, R, Soliman, SSM, Soraneh, S, Stoesser, N, Stoeva, TZ, Swain, CK, Szarpak, L, T Y, SS, Tabatabai, S, Ahmad, A, Tabche, C, Taha, ZM-A, Tan, K-K, Tasak, N, Tat, NY, Thaiprakong, A, Thangaraju, P, Tigoi, CC, Tiwari, K, Tovani-Palone, MR, Ahmad, S, Tran, TH, Tumurkhuu, M, Turner, P, Udoakang, AJ, Udoh, A, Ullah, N, Ullah, S, Vaithinathan, AG, Valenti, M, Vos, T, Ahmad, T, Vu, HTL, Waheed, Y, Walker, AS, Walson, JL, Wangrangsimakul, T, Weerakoon, KG, Wertheim, HFL, Williams, PCM, Wolde, AA, Wozniak, TM, Ahmadi, A, Wu, F, Wu, Z, Yadav, MKK, Yaghoubi, S, Yahaya, ZS, Yarahmadi, A, Yezli, S, Yismaw, YE, Yon, DK, Yuan, C-W, Ahmed, A, Yusuf, H, Zakham, F, Zamagni, G, Zhang, H, Zhang, Z-J, Zielińska, M, Zumla, A, Zyoud, SHH, Zyoud, SH, Hay, SI, Ahmed, H, Stergachis, A, Sartorius, B, Cooper, BS, Dolecek, C, Murray, CJL, Ahmed, I, Ahmed, M, Ahmed, S, Ahmed, SA, Akkaif, MA, Al Awaidy, S, Al Thaher, Y, Alalalmeh, SO, AlBataineh, MT, Aldhaleei, WA, Al-Gheethi, AAS, Alhaji, NB, Ali, A, Ali, L, Ali, SS, Ali, W, Allel, K, Al-Marwani, S, Alrawashdeh, A, Altaf, A, Al-Tammemi, AB, Al-Tawfiq, JA, Alzoubi, KH, Al-Zyoud, WA, Amos, B, Amuasi, JH, Ancuceanu, R, Andrews, JR, Anil, A, Anuoluwa, IA, Anvari, S, Anyasodor, AE, Apostol, GLC, Arabloo, J, Arafat, M, Aravkin, AY, Areda, D, Aremu, A, Artamonov, AA, Ashley, EA, Asika, MO, Athari, SS, Atout, MMW, Awoke, T, Azadnajafabad, S, Azam, JM, Aziz, S, Naghavi, M, Vollset, SE, Ikuta, KS, Swetschinski, LR, Gray, AP, Wool, EE, Robles Aguilar, G, Mestrovic, T, Smith, G, Han, C, Hsu, RL, Azzam, AY, Babaei, M, Babin, F-X, Badar, M, Baig, AA, Bajcetic, M, Baker, S, Bardhan, M, Barqawi, HJ, Basharat, Z, Chalek, J, Basiru, A, Bastard, M, Basu, S, Bayleyegn, NS, Belete, MA, Bello, OO, Beloukas, A, Berkley, JA, Bhagavathula, AS, Bhaskar, S, Araki, DT, Bhuyan, SS, Bielicki, JA, Briko, NI, Brown, CS, Browne, AJ, Buonsenso, D, Bustanji, Y, Carvalheiro, CG, Castañeda-Orjuela, CA, Cenderadewi, M, Chung, E, Chadwick, J, Chakraborty, S, Chandika, RM, Chandy, S, Chansamouth, V, Chattu, VK, Chaudhary, AA, Ching, PR, Chopra, H, Chowdhury, FR, Raggi, C, Chu, D-T, Chutiyami, M, Cruz-Martins, N, da Silva, AG, Dadras, O, Dai, X, Darcho, SD, Das, S, De la Hoz, FP, Dekker, DM, Gershberg Hayoon, A, Dhama, K, Diaz, D, Dickson, BFR, Djorie, SG, Dodangeh, M, Dohare, S, Dokova, KG, Doshi, OP, Dowou, RK, Dsouza, HL, Davis Weaver, N, Dunachie, SJ, Dziedzic, AM, Eckmanns, T, Ed-Dra, A, Eftekharimehrabad, A, Ekundayo, TC, El Sayed, I, Elhadi, M, El-Huneidi, W, Elias, C, Lindstedt, PA, Ellis, SJ, Elsheikh, R, Elsohaby, I, Eltaha, C, Eshrati, B, Eslami, M, Eyre, DW, Fadaka, AO, Fagbamigbe, AF, Fahim, A, Smith, AE, Fakhri-Demeshghieh, A, Fasina, FO, Fasina, MM, Fatehizadeh, A, Feasey, NA, Feizkhah, A, Fekadu, G, Fischer, F, Fitriana, I, Forrest, KM, Altay, U, Fortuna Rodrigues, C, Fuller, JE, Gadanya, MA, Gajdács, M, Gandhi, AP, Garcia-Gallo, EE, Garrett, DO, Gautam, RK, Gebregergis, MW, Gebrehiwot, M, Bhattacharjee, NV, Gebremeskel, TG, Geffers, C, Georgalis, L, Ghazy, RM, Golechha, M, Golinelli, D, Gordon, M, Gulati, S, Gupta, RD, Gupta, S, Giannakis, K, Gupta, VK, Habteyohannes, AD, Haller, S, Harapan, H, Harrison, ML, Hasaballah, AI, Hasan, I, Hasan, RS, Hasani, H, Haselbeck, AH, Fell, F, Hasnain, MS, Hassan, II, Hassan, S, Hassan Zadeh Tabatabaei, MS, Hayat, K, He, J, Hegazi, OE, Heidari, M, Hezam, K, Holla, R, McManigal, B, Holm, M, Hopkins, H, Hossain, MM, Hosseinzadeh, M, Hostiuc, S, Hussein, NR, Huy, LD, Ibáñez-Prada, ED, Ikiroma, A, Ilic, IM, Ekapirat, N, Islam, SMS, Ismail, F, Ismail, NE, Iwu, CD, Iwu-Jaja, CJ, Jafarzadeh, A, Jaiteh, F, Jalilzadeh Yengejeh, R, Jamora, RDG, Javidnia, J, Mendes, JA, Jawaid, T, Jenney, AWJ, Jeon, HJ, Jokar, M, Jomehzadeh, N, Joo, T, Joseph, N, Kamal, Z, Kanmodi, KK, Kantar, RS, Runghien, T, Kapisi, JA, Karaye, IM, Khader, YS, Khajuria, H, Khalid, N, Khamesipour, F, Khan, A, Khan, MJ, Khan, MT, Khanal, V, Srimokla, O, Khidri, FF, Khubchandani, J, Khusuwan, S, Kim, MS, Kisa, A, Korshunov, VA, Krapp, F, Krumkamp, R, Kuddus, M, Kulimbet, M, Abdelkader, A, Kumar, D, Kumaran, EAP, Kuttikkattu, A, Kyu, HH, Landires, I, Lawal, BK, Le, TTT, Lederer, IM, Lee, M, Lee, SW, Abd-Elsalam, S, Lepape, A, Lerango, TL, Ligade, VS, Lim, C, Lim, SS, Limenh, LW, Liu, C, Liu, X, Loftus, MJ, Aboagye, RG, M Amin, HI, Maass, KL, Maharaj, SB, Mahmoud, MA, Maikanti-Charalampous, P, Makram, OM, Malhotra, K, Malik, AA, Mandilara, GD, Marks, F, Abolhassani, H, Martinez-Guerra, BA, Martorell, M, Masoumi-Asl, H, Mathioudakis, AG, May, J, McHugh, TA, Meiring, J, Meles, HN, Melese, A, Melese, EB, Abualruz, H, Minervini, G, Mohamed, NS, Mohammed, S, Mohan, S, Mokdad, AH, Monasta, L, Moodi Ghalibaf, A, Moore, CE, Moradi, Y, Mossialos, E, Abubakar, U, Mougin, V, Mukoro, GD, Mulita, F, Muller-Pebody, B, Murillo-Zamora, E, Musa, S, Musicha, P, Musila, LA, Muthupandian, S, Nagarajan, AJ, Abukhadijah, HJ, Naghavi, P, Nainu, F, Nair, TS, Najmuldeen, HHR, Natto, ZS, Nauman, J, Nayak, BP, Nchanji, GT, Ndishimye, P, Negoi, I, Aburuz, S, Negoi, RI, Nejadghaderi, SA, Nguyen, QP, Noman, EA, Nwakanma, DC, O'Brien, S, Ochoa, TJ, Odetokun, IA, Ogundijo, OA, Ojo-Akosile, TR, Abu-Zaid, A, Okeke, SR, Okonji, OC, Olagunju, AT, Olivas-Martinez, A, Olorukooba, AA, Olwoch, P, Onyedibe, KI, Ortiz-Brizuela, E, Osuolale, O, Ounchanum, P, Achalapong, S, Oyeyemi, OT, P A, MP, Paredes, JL, Parikh, RR, Patel, J, Patil, S, Pawar, S, Peleg, AY, Peprah, P, Perdigão, J, Addo, IY, Perrone, C, Petcu, I-R, Phommasone, K, Piracha, ZZ, Poddighe, D, Pollard, AJ, Poluru, R, Ponce-De-Leon, A, Puvvula, J, Qamar, FN, Adekanmbi, V, Qasim, NH, Rafai, CD, Raghav, P, Rahbarnia, L, Rahim, F, Rahimi-Movaghar, V, Rahman, M, Rahman, MA, Ramadan, H, Ramasamy, SK, Adeyeoluwa, TE, Ramesh, PS, Ramteke, PW, Rana, RK, Rani, U, Rashidi, M-M, Rathish, D, Rattanavong, S, Rawaf, S, Redwan, EMM, Reyes, LF, Adnani, QES, Roberts, T, Robotham, JV, Rosenthal, VD, Ross, AG, Roy, N, Rudd, KE, Sabet, CJ, Saddik, BA, Saeb, MR, Saeed, U, Adzigbli, LA, Saeedi Moghaddam, S, Saengchan, W, Safaei, M, Saghazadeh, A, Saheb Sharif-Askari, N, Sahebkar, A, Sahoo, SS, Sahu, M, Saki, M, Salam, N, Afzal, MS, Saleem, Z, Saleh, MA, Samodra, YL, Samy, AM, Saravanan, A, Satpathy, M, Schumacher, AE, Sedighi, M, Seekaew, S, Shafie, M, Afzal, S, Shah, PA, Shahid, S, Shahwan, MJ, Shakoor, S, Shalev, N, Shamim, MA, Shamshirgaran, MA, Shamsi, A, Sharifan, A, Shastry, RP, Agodi, A, Shetty, M, Shittu, A, Shrestha, S, Siddig, EE, Sideroglou, T, Sifuentes-Osornio, J, Silva, LMLR, Simões, EAF, Simpson, AJH, Singh, A, Ahlstrom, AJ, Singh, S, Sinto, R, Soliman, SSM, Soraneh, S, Stoesser, N, Stoeva, TZ, Swain, CK, Szarpak, L, T Y, SS, Tabatabai, S, Ahmad, A, Tabche, C, Taha, ZM-A, Tan, K-K, Tasak, N, Tat, NY, Thaiprakong, A, Thangaraju, P, Tigoi, CC, Tiwari, K, Tovani-Palone, MR, Ahmad, S, Tran, TH, Tumurkhuu, M, Turner, P, Udoakang, AJ, Udoh, A, Ullah, N, Ullah, S, Vaithinathan, AG, Valenti, M, Vos, T, Ahmad, T, Vu, HTL, Waheed, Y, Walker, AS, Walson, JL, Wangrangsimakul, T, Weerakoon, KG, Wertheim, HFL, Williams, PCM, Wolde, AA, Wozniak, TM, Ahmadi, A, Wu, F, Wu, Z, Yadav, MKK, Yaghoubi, S, Yahaya, ZS, Yarahmadi, A, Yezli, S, Yismaw, YE, Yon, DK, Yuan, C-W, Ahmed, A, Yusuf, H, Zakham, F, Zamagni, G, Zhang, H, Zhang, Z-J, Zielińska, M, Zumla, A, Zyoud, SHH, Zyoud, SH, Hay, SI, Ahmed, H, Stergachis, A, Sartorius, B, Cooper, BS, Dolecek, C, Murray, CJL, Ahmed, I, Ahmed, M, Ahmed, S, Ahmed, SA, Akkaif, MA, Al Awaidy, S, Al Thaher, Y, Alalalmeh, SO, AlBataineh, MT, Aldhaleei, WA, Al-Gheethi, AAS, Alhaji, NB, Ali, A, Ali, L, Ali, SS, Ali, W, Allel, K, Al-Marwani, S, Alrawashdeh, A, Altaf, A, Al-Tammemi, AB, Al-Tawfiq, JA, Alzoubi, KH, Al-Zyoud, WA, Amos, B, Amuasi, JH, Ancuceanu, R, Andrews, JR, Anil, A, Anuoluwa, IA, Anvari, S, Anyasodor, AE, Apostol, GLC, Arabloo, J, Arafat, M, Aravkin, AY, Areda, D, Aremu, A, Artamonov, AA, Ashley, EA, Asika, MO, Athari, SS, Atout, MMW, Awoke, T, Azadnajafabad, S, Azam, JM, and Aziz, S

Published
2024

15. Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050

Author

Naghavi, Mohsen, Vollset, Stein Emil, Ikuta, Kevin S, Swetschinski, Lucien R, Gray, Authia P, Wool, Eve E, Robles Aguilar, Gisela, Mestrovic, Tomislav, Smith, Georgia, Han, Chieh, Hsu, Rebecca L, Chalek, Julian, Araki, Daniel T, Chung, Erin, Raggi, Catalina, Gershberg Hayoon, Anna, Davis Weaver, Nicole, Lindstedt, Paulina A, Smith, Amanda E, Altay, Umut, Bhattacharjee, Natalia V, Giannakis, Konstantinos, Fell, Frederick, McManigal, Barney, Ekapirat, Nattwut, Mendes, Jessica Andretta, Runghien, Tilleye, Srimokla, Oraya, Abdelkader, Atef, Abd-Elsalam, Sherief, Aboagye, Richard Gyan, Abolhassani, Hassan, Abualruz, Hasan, Abubakar, Usman, Abukhadijah, Hana J, Aburuz, Salahdein, Abu-Zaid, Ahmed, Achalapong, Sureerak, Addo, Isaac Yeboah, Adekanmbi, Victor, Adeyeoluwa, Temitayo Esther, Adnani, Qorinah Estiningtyas Sakilah, Adzigbli, Leticia Akua, Afzal, Muhammad Sohail, Afzal, Saira, Agodi, Antonella, Ahlstrom, Austin J, Ahmad, Aqeel, Ahmad, Sajjad, Ahmad, Tauseef, Ahmadi, Ali, Ahmed, Ayman, Ahmed, Haroon, Ahmed, Ibrar, Ahmed, Mohammed, Ahmed, Saeed, Ahmed, Syed Anees, Akkaif, Mohammed Ahmed, Al Awaidy, Salah, Al Thaher, Yazan, Alalalmeh, Samer O, AlBataineh, Mohammad T, Aldhaleei, Wafa A, Al-Gheethi, Adel Ali Saeed, Alhaji, Nma Bida, Ali, Abid, Ali, Liaqat, Ali, Syed Shujait, Ali, Waad, Allel, Kasim, Al-Marwani, Sabah, Alrawashdeh, Ahmad, Altaf, Awais, Al-Tammemi, Alaa B., Al-Tawfiq, Jaffar A, Alzoubi, Karem H, Al-Zyoud, Walid Adnan, Amos, Ben, Amuasi, John H, Ancuceanu, Robert, Andrews, Jason R, Anil, Abhishek, Anuoluwa, Iyadunni Adesola, Anvari, Saeid, Anyasodor, Anayochukwu Edward, Apostol, Geminn Louis Carace, Arabloo, Jalal, Arafat, Mosab, Aravkin, Aleksandr Y, Areda, Demelash, Aremu, Abdulfatai, Artamonov, Anton A, Ashley, Elizabeth A, Asika, Marvellous O, Athari, Seyyed Shamsadin, Atout, Maha Moh'd Wahbi, Awoke, Tewachew, Azadnajafabad, Sina, Azam, James Mba, Aziz, Shahkaar, Azzam, Ahmed Y., Babaei, Mahsa, Babin, Francois-Xavier, Badar, Muhammad, Baig, Atif Amin, Bajcetic, Milica, Baker, Stephen, Bardhan, Mainak, Barqawi, Hiba Jawdat, Basharat, Zarrin, Basiru, Afisu, Bastard, Mathieu, Basu, Saurav, Bayleyegn, Nebiyou Simegnew, Belete, Melaku Ashagrie, Bello, Olorunjuwon Omolaja, Beloukas, Apostolos, Berkley, James A, Bhagavathula, Akshaya Srikanth, Bhaskar, Sonu, Bhuyan, Soumitra S, Bielicki, Julia A, Briko, Nikolay Ivanovich, Brown, Colin Stewart, Browne, Annie J, Buonsenso, Danilo, Bustanji, Yasser, Carvalheiro, Cristina G, Castañeda-Orjuela, Carlos A, Cenderadewi, Muthia, Chadwick, Joshua, Chakraborty, Sandip, Chandika, Rama Mohan, Chandy, Sara, Chansamouth, Vilada, Chattu, Vijay Kumar, Chaudhary, Anis Ahmad, Ching, Patrick R, Chopra, Hitesh, Chowdhury, Fazle Rabbi, Chu, Dinh-Toi, Chutiyami, Muhammad, Cruz-Martins, Natalia, da Silva, Alanna Gomes, Dadras, Omid, Dai, Xiaochen, Darcho, Samuel D, Das, Saswati, De la Hoz, Fernando Pio, Dekker, Denise Myriam, Dhama, Kuldeep, Diaz, Daniel, Dickson, Benjamin Felix Rothschild, Djorie, Serge Ghislain, Dodangeh, Milad, Dohare, Sushil, Dokova, Klara Georgieva, Doshi, Ojas Prakashbhai, Dowou, Robert Kokou, Dsouza, Haneil Larson, Dunachie, Susanna J, Dziedzic, Arkadiusz Marian, Eckmanns, Tim, Ed-Dra, Abdelaziz, Eftekharimehrabad, Aziz, Ekundayo, Temitope Cyrus, El Sayed, Iman, Elhadi, Muhammed, El-Huneidi, Waseem, Elias, Christelle, Ellis, Sally J, Elsheikh, Randa, Elsohaby, Ibrahim, Eltaha, Chadi, Eshrati, Babak, Eslami, Majid, Eyre, David William, Fadaka, Adewale Oluwaseun, Fagbamigbe, Adeniyi Francis, Fahim, Ayesha, Fakhri-Demeshghieh, Aliasghar, Fasina, Folorunso Oludayo, Fasina, Modupe Margaret, Fatehizadeh, Ali, Feasey, Nicholas A, Feizkhah, Alireza, Fekadu, Ginenus, Fischer, Florian, Fitriana, Ida, Forrest, Karen M, Fortuna Rodrigues, Celia, Fuller, John E, Gadanya, Muktar A, Gajdács, Márió, Gandhi, Aravind P, Garcia-Gallo, Esteban E, Garrett, Denise O, Gautam, Rupesh K, Gebregergis, Miglas Welay, Gebrehiwot, Mesfin, Gebremeskel, Teferi Gebru, Geffers, Christine, Georgalis, Leonidas, Ghazy, Ramy Mohamed, Golechha, Mahaveer, Golinelli, Davide, Gordon, Melita, Gulati, Snigdha, Gupta, Rajat Das, Gupta, Sapna, Gupta, Vijai Kumar, Habteyohannes, Awoke Derbie, Haller, Sebastian, Harapan, Harapan, Harrison, Michelle L, Hasaballah, Ahmed I, Hasan, Ikramul, Hasan, Rumina Syeda, Hasani, Hamidreza, Haselbeck, Andrea Haekyung, Hasnain, Md Saquib, Hassan, Ikrama Ibrahim, Hassan, Shoaib, Hassan Zadeh Tabatabaei, Mahgol Sadat, Hayat, Khezar, He, Jiawei, Hegazi, Omar E, Heidari, Mohammad, Hezam, Kamal, Holla, Ramesh, Holm, Marianne, Hopkins, Heidi, Hossain, Md Mahbub, Hosseinzadeh, Mehdi, Hostiuc, Sorin, Hussein, Nawfal R, Huy, Le Duc, Ibáñez-Prada, Elsa D, Ikiroma, Adalia, Ilic, Irena M, Islam, Sheikh Mohammed Shariful, Ismail, Faisal, Ismail, Nahlah Elkudssiah, Iwu, Chidozie Declan, Iwu-Jaja, Chinwe Juliana, Jafarzadeh, Abdollah, Jaiteh, Fatoumatta, Jalilzadeh Yengejeh, Reza, Jamora, Roland Dominic G, Javidnia, Javad, Jawaid, Talha, Jenney, Adam W J, Jeon, Hyon Jin, Jokar, Mohammad, Jomehzadeh, Nabi, Joo, Tamas, Joseph, Nitin, Kamal, Zul, Kanmodi, Kehinde Kazeem, Kantar, Rami S, Kapisi, James Apollo, Karaye, Ibraheem M, Khader, Yousef Saleh, Khajuria, Himanshu, Khalid, Nauman, Khamesipour, Faham, Khan, Ajmal, Khan, Mohammad Jobair, Khan, Muhammad Tariq, Khanal, Vishnu, Khidri, Feriha Fatima, Khubchandani, Jagdish, Khusuwan, Suwimon, Kim, Min Seo, Kisa, Adnan, Korshunov, Vladimir Andreevich, Krapp, Fiorella, Krumkamp, Ralf, Kuddus, Mohammed, Kulimbet, Mukhtar, Kumar, Dewesh, Kumaran, Emmanuelle A P, Kuttikkattu, Ambily, Kyu, Hmwe Hmwe, Landires, Iván, Lawal, Basira Kankia, Le, Thao Thi Thu, Lederer, Ingeborg Maria, Lee, Munjae, Lee, Seung Won, Lepape, Alain, Lerango, Temesgen Leka, Ligade, Virendra S, Lim, Cherry, Lim, Stephen S, Limenh, Liknaw Workie, Liu, Chaojie, Liu, Xiaofeng, Liu, Xuefeng, Loftus, Michael J, M Amin, Hawraz Ibrahim, Maass, Kelsey Lynn, Maharaj, Sandeep B, Mahmoud, Mansour Adam, Maikanti-Charalampous, Panagiota, Makram, Omar M, Malhotra, Kashish, Malik, Ahmad Azam, Mandilara, Georgia D, Marks, Florian, Martinez-Guerra, Bernardo Alfonso, Martorell, Miquel, Masoumi-Asl, Hossein, Mathioudakis, Alexander G, May, Juergen, McHugh, Theresa A, Meiring, James, Meles, Hadush Negash, Melese, Addisu, Melese, Endalkachew Belayneh, Minervini, Giuseppe, Mohamed, Nouh Saad, Mohammed, Shafiu, Mohan, Syam, Mokdad, Ali H, Monasta, Lorenzo, Moodi Ghalibaf, AmirAli, Moore, Catrin E, Moradi, Yousef, Mossialos, Elias, Mougin, Vincent, Mukoro, George Duke, Mulita, Francesk, Muller-Pebody, Berit, Murillo-Zamora, Efren, Musa, Sani, Musicha, Patrick, Musila, Lillian A, Muthupandian, Saravanan, Nagarajan, Ahamarshan Jayaraman, Naghavi, Pirouz, Nainu, Firzan, Nair, Tapas Sadasivan, Najmuldeen, Hastyar Hama Rashid, Natto, Zuhair S, Nauman, Javaid, Nayak, Biswa Prakash, Nchanji, G Takop, Ndishimye, Pacifique, Negoi, Ionut, Negoi, Ruxandra Irina, Nejadghaderi, Seyed Aria, Nguyen, QuynhAnh P, Noman, Efaq Ali, Nwakanma, Davis C, O'Brien, Seamus, Ochoa, Theresa J, Odetokun, Ismail A, Ogundijo, Oluwaseun Adeolu, Ojo-Akosile, Tolulope R, Okeke, Sylvester Reuben, Okonji, Osaretin Christabel, Olagunju, Andrew T, Olivas-Martinez, Antonio, Olorukooba, Abdulhakeem Abayomi, Olwoch, Peter, Onyedibe, Kenneth Ikenna, Ortiz-Brizuela, Edgar, Osuolale, Olayinka, Ounchanum, Pradthana, Oyeyemi, Oyetunde T, P A, Mahesh Padukudru, Paredes, Jose L, Parikh, Romil R, Patel, Jay, Patil, Shankargouda, Pawar, Shrikant, Peleg, Anton Y, Peprah, Prince, Perdigão, João, Perrone, Carlo, Petcu, Ionela-Roxana, Phommasone, Koukeo, Piracha, Zahra Zahid, Poddighe, Dimitri, Pollard, Andrew J, Poluru, Ramesh, Ponce-De-Leon, Alfredo, Puvvula, Jagadeesh, Qamar, Farah Naz, Qasim, Nameer Hashim, Rafai, Clotaire Donatien, Raghav, Pankaja, Rahbarnia, Leila, Rahim, Fakher, Rahimi-Movaghar, Vafa, Rahman, Mosiur, Rahman, Muhammad Aziz, Ramadan, Hazem, Ramasamy, Shakthi Kumaran, Ramesh, Pushkal Sinduvadi, Ramteke, Pramod W, Rana, Rishabh Kumar, Rani, Usha, Rashidi, Mohammad-Mahdi, Rathish, Devarajan, Rattanavong, Sayaphet, Rawaf, Salman, Redwan, Elrashdy Moustafa Mohamed, Reyes, Luis Felipe, Roberts, Tamalee, Robotham, Julie V, Rosenthal, Victor Daniel, Ross, Allen Guy, Roy, Nitai, Rudd, Kristina E, Sabet, Cameron John, Saddik, Basema Ahmad, Saeb, Mohammad Reza, Saeed, Umar, Saeedi Moghaddam, Sahar, Saengchan, Weeravoot, Safaei, Mohsen, Saghazadeh, Amene, Saheb Sharif-Askari, Narjes, Sahebkar, Amirhossein, Sahoo, Soumya Swaroop, Sahu, Maitreyi, Saki, Morteza, Salam, Nasir, Saleem, Zikria, Saleh, Mohamed A, Samodra, Yoseph Leonardo, Samy, Abdallah M, Saravanan, Aswini, Satpathy, Maheswar, Schumacher, Austin E, Sedighi, Mansour, Seekaew, Samroeng, Shafie, Mahan, Shah, Pritik A, Shahid, Samiah, Shahwan, Moyad Jamal, Shakoor, Sadia, Shalev, Noga, Shamim, Muhammad Aaqib, Shamshirgaran, Mohammad Ali, Shamsi, Anas, Sharifan, Amin, Shastry, Rajesh P, Shetty, Mahabalesh, Shittu, Aminu, Shrestha, Sunil, Siddig, Emmanuel Edwar, Sideroglou, Theologia, Sifuentes-Osornio, Jose, Silva, Luís Manuel Lopes Rodrigues, Simões, Eric A F, Simpson, Andrew J H, Singh, Amit, Singh, Surjit, Sinto, Robert, Soliman, Sameh S M, Soraneh, Soroush, Stoesser, Nicole, Stoeva, Temenuga Zhekova, Swain, Chandan Kumar, Szarpak, Lukasz, T Y, Sree Sudha, Tabatabai, Shima, Tabche, Celine, Taha, Zanan Mohammed-Ameen, Tan, Ker-Kan, Tasak, Nidanuch, Tat, Nathan Y, Thaiprakong, Areerat, Thangaraju, Pugazhenthan, Tigoi, Caroline Chepngeno, Tiwari, Krishna, Tovani-Palone, Marcos Roberto, Tran, Thang Huu, Tumurkhuu, Munkhtuya, Turner, Paul, Udoakang, Aniefiok John, Udoh, Arit, Ullah, Noor, Ullah, Saeed, Vaithinathan, Asokan Govindaraj, Valenti, Mario, Vos, Theo, Vu, Huong T L, Waheed, Yasir, Walker, Ann Sarah, Walson, Judd L, Wangrangsimakul, Tri, Weerakoon, Kosala Gayan, Wertheim, Heiman F L, Williams, Phoebe C M, Wolde, Asrat Arja, Wozniak, Teresa M, Wu, Felicia, Wu, Zenghong, Yadav, Mukesh Kumar Kumar, Yaghoubi, Sajad, Yahaya, Zwanden Sule, Yarahmadi, Amir, Yezli, Saber, Yismaw, Yazachew Engida, Yon, Dong Keon, Yuan, Chun-Wei, Yusuf, Hadiza, Zakham, Fathiah, Zamagni, Giulia, Zhang, Haijun, Zhang, Zhi-Jiang, Zielińska, Magdalena, Zumla, Alimuddin, Zyoud, Sa'ed H. H, Zyoud, Samer H, Hay, Simon I, Stergachis, Andy, Sartorius, Benn, Cooper, Ben S, Dolecek, Christiane, and Murray, Christopher J L

Abstract

Antimicrobial resistance (AMR) poses an important global health challenge in the 21st century. A previous study has quantified the global and regional burden of AMR for 2019, followed with additional publications that provided more detailed estimates for several WHO regions by country. To date, there have been no studies that produce comprehensive estimates of AMR burden across locations that encompass historical trends and future forecasts.

Published
2024
Full Text
View/download PDF

17. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis

Author

Murray, CJL, Ikuta, KS, Sharara, F, Swetschinski, L, Aguilar, GR, Gray, A, Han, C, Bisignano, C, Rao, P, Wool, E, Johnson, SC, Browne, AJ, Chipeta, MG, Fell, F, Hackett, S, Haines-Woodhouse, G, Hamadani, BHK, Kumaran, EAP, McManigal, B, Agarwal, R, Akech, S, Albertson, S, Amuasi, J, Andrews, J, Aravkin, A, Ashley, E, Bailey, F, Baker, S, Basnyat, B, Bekker, A, Bender, R, Bethou, A, Bielicki, J, Boonkasidecha, S, Bukosia, J, Carvalheiro, C, Castaneda-Orjuela, C, Chansamouth, V, Chaurasia, S, Chiurchiu, S, Chowdhury, F, Cook, AJ, Cooper, B, Cressey, TR, Criollo-Mora, E, Cunningham, M, Darboe, S, Day, NPJ, De Luca, M, Dokova, K, Dramowski, A, Dunachie, SJ, Eckmanns, T, Eibach, D, Emami, A, Feasey, N, Fisher-Pearson, N, Forrest, K, Garrett, D, Gastmeier, P, Giref, AZ, Greer, RC, Gupta, V, Haller, S, Haselbeck, A, Hay, S, Holm, M, Hopkins, S, Iregbu, KC, Jacobs, J, Jarovsky, D, Javanmardi, F, Khorana, M, Kissoon, N, Kobeissi, E, Kostyanev, T, Krapp, F, Krumkamp, R, Kumar, A, Kyu, HH, Lim, C, Limmathurotsakul, D, Loftus, MJ, Lunn, M, Ma, J, Mturi, N, Munera-Huertas, T, Musicha, P, Mussi-Pinhata, MM, Nakamura, T, Nanavati, R, Nangia, S, Newton, P, Ngoun, C, Novotney, A, Nwakanma, D, Obiero, CW, Olivas-Martinez, A, Olliaro, P, Ooko, E, Ortiz-Brizuela, E, Peleg, AY, Perrone, C, Plakkal, N, Ponce-de-Leon, A, Raad, M, Ramdin, T, Riddell, A, Roberts, T, VictoriaRobotham, J, Roca, A, Rudd, KE, Russell, N, Schnall, J, Scott, JAG, Shivamallappa, M, Sifuentes-Osornio, J, Steenkeste, N, Stewardson, AJ, Stoeva, T, Tasak, N, Thaiprakong, A, Thwaites, G, Turner, C, Turner, P, van Doorn, HR, Velaphi, S, Vongpradith, A, Huong, V, Walsh, T, Waner, S, Wangrangsimakul, T, Wozniak, T, Zheng, P, Sartorius, B, Lopez, AD, Stergachis, A, Moore, C, Dolecek, C, Naghavi, M, Murray, CJL, Ikuta, KS, Sharara, F, Swetschinski, L, Aguilar, GR, Gray, A, Han, C, Bisignano, C, Rao, P, Wool, E, Johnson, SC, Browne, AJ, Chipeta, MG, Fell, F, Hackett, S, Haines-Woodhouse, G, Hamadani, BHK, Kumaran, EAP, McManigal, B, Agarwal, R, Akech, S, Albertson, S, Amuasi, J, Andrews, J, Aravkin, A, Ashley, E, Bailey, F, Baker, S, Basnyat, B, Bekker, A, Bender, R, Bethou, A, Bielicki, J, Boonkasidecha, S, Bukosia, J, Carvalheiro, C, Castaneda-Orjuela, C, Chansamouth, V, Chaurasia, S, Chiurchiu, S, Chowdhury, F, Cook, AJ, Cooper, B, Cressey, TR, Criollo-Mora, E, Cunningham, M, Darboe, S, Day, NPJ, De Luca, M, Dokova, K, Dramowski, A, Dunachie, SJ, Eckmanns, T, Eibach, D, Emami, A, Feasey, N, Fisher-Pearson, N, Forrest, K, Garrett, D, Gastmeier, P, Giref, AZ, Greer, RC, Gupta, V, Haller, S, Haselbeck, A, Hay, S, Holm, M, Hopkins, S, Iregbu, KC, Jacobs, J, Jarovsky, D, Javanmardi, F, Khorana, M, Kissoon, N, Kobeissi, E, Kostyanev, T, Krapp, F, Krumkamp, R, Kumar, A, Kyu, HH, Lim, C, Limmathurotsakul, D, Loftus, MJ, Lunn, M, Ma, J, Mturi, N, Munera-Huertas, T, Musicha, P, Mussi-Pinhata, MM, Nakamura, T, Nanavati, R, Nangia, S, Newton, P, Ngoun, C, Novotney, A, Nwakanma, D, Obiero, CW, Olivas-Martinez, A, Olliaro, P, Ooko, E, Ortiz-Brizuela, E, Peleg, AY, Perrone, C, Plakkal, N, Ponce-de-Leon, A, Raad, M, Ramdin, T, Riddell, A, Roberts, T, VictoriaRobotham, J, Roca, A, Rudd, KE, Russell, N, Schnall, J, Scott, JAG, Shivamallappa, M, Sifuentes-Osornio, J, Steenkeste, N, Stewardson, AJ, Stoeva, T, Tasak, N, Thaiprakong, A, Thwaites, G, Turner, C, Turner, P, van Doorn, HR, Velaphi, S, Vongpradith, A, Huong, V, Walsh, T, Waner, S, Wangrangsimakul, T, Wozniak, T, Zheng, P, Sartorius, B, Lopez, AD, Stergachis, A, Moore, C, Dolecek, C, and Naghavi, M

Abstract

BACKGROUND: Antimicrobial resistance (AMR) poses a major threat to human health around the world. Previous publications have estimated the effect of AMR on incidence, deaths, hospital length of stay, and health-care costs for specific pathogen-drug combinations in select locations. To our knowledge, this study presents the most comprehensive estimates of AMR burden to date. METHODS: We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 23 pathogens and 88 pathogen-drug combinations in 204 countries and territories in 2019. We obtained data from systematic literature reviews, hospital systems, surveillance systems, and other sources, covering 471 million individual records or isolates and 7585 study-location-years. We used predictive statistical modelling to produce estimates of AMR burden for all locations, including for locations with no data. Our approach can be divided into five broad components: number of deaths where infection played a role, proportion of infectious deaths attributable to a given infectious syndrome, proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antibiotic of interest, and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden based on two counterfactuals: deaths attributable to AMR (based on an alternative scenario in which all drug-resistant infections were replaced by drug-susceptible infections), and deaths associated with AMR (based on an alternative scenario in which all drug-resistant infections were replaced by no infection). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. We present final estimates aggregated to the global and regional level. FINDINGS: On the bas

Published
2022

18. Hackathons as a means of accelerating scientific discoveries and knowledge transfer

Author

Ghouila, A, Siwo, G, Entfellner, J, Panji, S, Button-Simons, K, Davis, S, Fadlelmola, F, Ferdig, M, Mulder, N, Bensellak, T, Ghansah, A, Ghedira, K, Gritzman, A, Isewon, I, Kishk, A, Moussa, A, Loucoubar, C, Musicha, P, Pore, M, Sengeh, D, Mapiye, D, Rallabandi, P, and Varughese, M

Subjects
Resource, 0301 basic medicine, Biomedical Research, 020205 medical informatics, Plasmodium falciparum, 02 engineering and technology, Biology, South Africa, 03 medical and health sciences, Technology Transfer, 0202 electrical engineering, electronic engineering, information engineering, Genetics, Humans, Interdisciplinary communication, Cooperative Behavior, Malaria, Falciparum, Genetics (clinical), business.industry, Data science, Human knowledge, 030104 developmental biology, Workflow, Technology transfer, Interdisciplinary Communication, Cooperative behavior, business, Knowledge transfer, Malaria falciparum, Information Systems, Agile software development
Abstract

Scientific research plays a key role in the advancement of human knowledge and pursuit of solutions to important societal challenges. Typically, research occurs within specific institutions where data are generated and subsequently analyzed. Although collaborative science bringing together multiple institutions is now common, in such collaborations the analytical processing of the data is often performed by individual researchers within the team, with only limited internal oversight and critical analysis of the workflow prior to publication. Here, we show how hackathons can be a means of enhancing collaborative science by enabling peer review before results of analyses are published by cross-validating the design of studies or underlying data sets and by driving reproducibility of scientific analyses. Traditionally, in data analysis processes, data generators and bioinformaticians are divided and do not collaborate on analyzing the data. Hackathons are a good strategy to build bridges over the traditional divide and are potentially a great agile extension to the more structured collaborations between multiple investigators and institutions.

Published
2018
Full Text
View/download PDF

19. Association of shorter leucocyte telomere length with risk of frailty

Author

Bountziouka, Vasiliki, Nelson, Christopher P., Codd, Veryan, Wang, Qingning, Musicha, Crispin, Allara, Elias, Kaptoge, Stephen, Di Angelantonio, Emanuele, Butterworth, Adam S., Thompson, John R., Curtis, Elizabeth M., Wood, Angela M., Danesh, John N., Harvey, Nicholas C., Cooper, Cyrus, and Samani, Nilesh J.

Abstract

Frailty is a multidimensional syndrome of decline that affects multiple systems and predisposes to adverse health outcomes. Although chronological age is the major risk factor, inter‐individual variation in risk is not fully understood. Leucocyte telomere length (LTL), a proposed marker of biological age, has been associated with risk of many diseases. We sought to determine whether LTL is associated with risk of frailty. We utilized cross‐sectional data from 441 781 UK Biobank participants (aged 40–69 years), with complete data on frailty indicators and LTL. Frailty was defined as the presence of at least three of five indicators: weaker grip strength, slower walking pace, weight loss in the past year, lower physical activity, and exhaustion in the past 2 weeks. LTL was measured using a validated qPCR method and reported as a ratio of the telomere repeat number (T) to a single‐copy gene (S) (T/S ratio). Association of LTL with frailty was evaluated using adjusted (chronological age, sex, deprivation, smoking, alcohol intake, body mass index, and multimorbidity) multinomial and ordinal regression models, and results are presented as relative risk (RRR) or odds ratios (OR), respectively, alongside the 95% confidence interval (CI). Mendelian randomization (MR), using 131 genetic variants associated with LTL, was used to assess if the association of LTL with frailty was causal. Frail participants (4.6%) were older (median age difference (95% CI): 3 (2.5; 3.5) years, P= 2.73 × 10−33), more likely to be female (61%, P= 1.97 × 10−129), and had shorter LTL (−0.13SD vs. 0.03SD, P= 5.43 × 10−111) than non‐frail. In adjusted analyses, both age and LTL were associated with frailty (RRR = 1.03 (95% CI: 1.02; 1.04) per year of older chronological age, P= 3.99 × 10−12; 1.10 (1.08; 1.11) per SD shorter LTL, P= 1.46 × 10−30). Within each age group (40–49, 50–59, 60–69 years), the prevalence of frailty was about 33% higher in participants with shorter (−2SD) versus longer telomeres (+2SD). MR analysis showed an association of LTL with frailty that was directionally consistent with the observational association, but not statistically significant (MR‐Median: OR (95% CI): 1.08 (0.98; 1.19) per SD shorter LTL, P= 0.13). Inter‐individual variation in LTL is associated with the risk of frailty independently of chronological age and other risk factors. Our findings provide evidence for an additional biological determinant of frailty.

Published
2022
Full Text
View/download PDF

20. Emerging resistance to empiric antimicrobial regimens for pediatric bloodstream infections in Malawi (1998-2017)

Author

Iroh Tam, P, Musicha, P, Kawaza, K, Cornick, J, Denis, B, Freyne, B, Everett, D, Dube, Q, French, N, Feasey, N, and Heyderman, R

Subjects
Cross Infection, Malawi, Incidence, Gram negative, Infant, Bacteremia, Anti-Bacterial Agents, Hospitalization, neonatal, sepsis, pediatric, Blood Culture, Child, Preschool, Drug Resistance, Multiple, Bacterial, Prevalence, Humans, antimicrobial resistance, Gram-Negative Bacterial Infections, Articles and Commentaries, Gram-Positive Bacterial Infections
Abstract

Background The adequacy of the World Health Organization’s Integrated Management of Childhood Illness (IMCI) antimicrobial guidelines for the treatment of suspected severe bacterial infections is dependent on a low prevalence of antimicrobial resistance (AMR). We describe trends in etiologies and susceptibility patterns of bloodstream infections (BSI) in hospitalized children in Malawi. Methods We determined the change in the population-based incidence of BSI in children admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi (1998–2017). AMR profiles were assessed by the disc diffusion method, and trends over time were evaluated. Results A total 89643 pediatric blood cultures were performed, and 10621 pathogens were included in the analysis. Estimated minimum incidence rates of BSI for those ≤5 years of age fell from a peak of 11.4 per 1000 persons in 2002 to 3.4 per 1000 persons in 2017. Over 2 decades, the resistance of Gram-negative pathogens to all empiric, first-line antimicrobials (ampicillin/penicillin, gentamicin, ceftriaxone) among children ≤5 years increased from 3.4% to 30.2% (P < .001). Among those ≤60 days, AMR to all first-line antimicrobials increased from 7.0% to 67.7% (P < .001). Among children ≤5 years, Klebsiella spp. resistance to all first-line antimicrobial regimens increased from 5.9% to 93.7% (P < .001). Conclusions The incidence of BSI among hospitalized children has decreased substantially over the last 20 years, although gains have been offset by increases in Gram-negative pathogens’ resistance to all empiric first-line antimicrobials. There is an urgent need to address the broader challenge of adapting IMCI guidelines to the local setting in the face of rapidly-expanding AMR in childhood BSI., Incidences of bloodstream infections in Malawian children declined significantly over 2 decades, but resistance of Gram-negative pathogens to empiric, first-line antimicrobials increased from 3.4% to 30.2% for children ≤5 years and 7.0% to 67.7% for young infants ≤60 days.

Published
2019
Full Text
View/download PDF

21. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis

Author

Murray, Christopher J L, Ikuta, Kevin Shunji, Sharara, Fablina, Swetschinski, Lucien, Robles Aguilar, Gisela, Gray, Authia, Han, Chieh, Bisignano, Catherine, Rao, Puja, Wool, Eve, Johnson, Sarah C, Browne, Annie J, Chipeta, Michael Give, Fell, Frederick, Hackett, Sean, Haines-Woodhouse, Georgina, Kashef Hamadani, Bahar H, Kumaran, Emmanuelle A P, McManigal, Barney, Achalapong, Sureeruk, Agarwal, Ramesh, Akech, Samuel, Albertson, Samuel, Amuasi, John, Andrews, Jason, Aravkin, Aleskandr, Ashley, Elizabeth, Babin, François-Xavier, Bailey, Freddie, Baker, Stephen, Basnyat, Buddha, Bekker, Adrie, Bender, Rose, Berkley, James A, Bethou, Adhisivam, Bielicki, Julia, Boonkasidecha, Suppawat, Bukosia, James, Carvalheiro, Cristina, Castañeda-Orjuela, Carlos, Chansamouth, Vilada, Chaurasia, Suman, Chiurchiù, Sara, Chowdhury, Fazle, Clotaire Donatien, Rafai, Cook, Aislinn J, Cooper, Ben, Cressey, Tim R, Criollo-Mora, Elia, Cunningham, Matthew, Darboe, Saffiatou, Day, Nicholas P J, De Luca, Maia, Dokova, Klara, Dramowski, Angela, Dunachie, Susanna J, Duong Bich, Thuy, Eckmanns, Tim, Eibach, Daniel, Emami, Amir, Feasey, Nicholas, Fisher-Pearson, Natasha, Forrest, Karen, Garcia, Coralith, Garrett, Denise, Gastmeier, Petra, Giref, Ababi Zergaw, Greer, Rachel Claire, Gupta, Vikas, Haller, Sebastian, Haselbeck, Andrea, Hay, Simon I, Holm, Marianne, Hopkins, Susan, Hsia, Yingfen, Iregbu, Kenneth C, Jacobs, Jan, Jarovsky, Daniel, Javanmardi, Fatemeh, Jenney, Adam W J, Khorana, Meera, Khusuwan, Suwimon, Kissoon, Niranjan, Kobeissi, Elsa, Kostyanev, Tomislav, Krapp, Fiorella, Krumkamp, Ralf, Kumar, Ajay, Kyu, Hmwe Hmwe, Lim, Cherry, Lim, Kruy, Limmathurotsakul, Direk, Loftus, Michael James, Lunn, Miles, Ma, Jianing, Manoharan, Anand, Marks, Florian, May, Jürgen, Mayxay, Mayfong, Mturi, Neema, Munera-Huertas, Tatiana, Musicha, Patrick, Musila, Lilian A, Mussi-Pinhata, Marisa Marcia, Naidu, Ravi Narayan, Nakamura, Tomoka, Nanavati, Ruchi, Nangia, Sushma, Newton, Paul, Ngoun, Chanpheaktra, Novotney, Amanda, Nwakanma, Davis, Obiero, Christina W, Ochoa, Theresa J, Olivas-Martinez, Antonio, Olliaro, Piero, Ooko, Ednah, Ortiz-Brizuela, Edgar, Ounchanum, Pradthana, Pak, Gideok D, Paredes, Jose Luis, Peleg, Anton Yariv, Perrone, Carlo, Phe, Thong, Phommasone, Koukeo, Plakkal, Nishad, Ponce-de-Leon, Alfredo, Raad, Mathieu, Ramdin, Tanusha, Rattanavong, Sayaphet, Riddell, Amy, Roberts, Tamalee, Robotham, Julie Victoria, Roca, Anna, Rosenthal, Victor Daniel, Rudd, Kristina E, Russell, Neal, Sader, Helio S, Saengchan, Weerawut, Schnall, Jesse, Scott, John Anthony Gerard, Seekaew, Samroeng, Sharland, Mike, Shivamallappa, Madhusudhan, Sifuentes-Osornio, Jose, Simpson, Andrew J, Steenkeste, Nicolas, Stewardson, Andrew James, Stoeva, Temenuga, Tasak, Nidanuch, Thaiprakong, Areerat, Thwaites, Guy, Tigoi, Caroline, Turner, Claudia, Turner, Paul, van Doorn, H Rogier, Velaphi, Sithembiso, Vongpradith, Avina, Vongsouvath, Manivanh, Vu, Huong, Walsh, Timothy, Walson, Judd L, Waner, Seymour, Wangrangsimakul, Tri, Wannapinij, Prapass, Wozniak, Teresa, Young Sharma, Tracey E M W, Yu, Kalvin C, Zheng, Peng, Sartorius, Benn, Lopez, Alan D, Stergachis, Andy, Moore, Catrin, Dolecek, Christiane, and Naghavi, Mohsen

Abstract

Antimicrobial resistance (AMR) poses a major threat to human health around the world. Previous publications have estimated the effect of AMR on incidence, deaths, hospital length of stay, and health-care costs for specific pathogen–drug combinations in select locations. To our knowledge, this study presents the most comprehensive estimates of AMR burden to date.

Published
2022
Full Text
View/download PDF

22. A novel air-dried multiplex high-resolution melt assay for the detection of extended-spectrum β-lactamase and carbapenemase genes

Author

Cubas-Atienzar, Ana I., Williams, Christopher T., Karkey, Abhilasha, Dongol, Sabina, Sulochana, Manandhar, Rajendra, Shrestha, Hobbs, Glyn, Evans, Katie, Musicha, Patrick, Feasey, Nicholas, Cuevas, Luis E., Adams, Emily R., and Edwards, Thomas

Abstract

•Development and evaluation of a novel air-dried HRM assay to detect eight major ESBL and carbapenemase genes.•Sensitivity and specificity of the air-dried HRM assay versus the reference molecular tests was 94.7–98.3% and 98.5–99.2%.•Assay had overall agreement of 91.1% in predicting phenotypic resistance to cefotaxime and meropenem in Enterobacteriaceae.•Cross-platform validation showed almost perfect reproducibility in five different qPCR platforms.•No loss of sensitivity was observed after 8 months of storage at room, refrigerator and oven temperatures.

Published
2021
Full Text
View/download PDF

23. Population genetic structure, antibiotic resistance, capsule switching and evolution of invasive pneumococci before conjugate vaccination in Malawi

Author

Chaguza, C, Cornick, J, Andam, C, Gladstone, R, Alaerts, M, Musicha, P, Peno, C, Bar-Zeev, N, Kamng'ona, A, Kiran, A, Msefula, C, McGee, L, Breiman, R, Kadioglu, A, French, N, Heyderman, R, Hanage, W, Bentley, S, and Everett, D

Subjects
Research Support, Non-U.S. Gov't, Journal Article, Human medicine
Abstract

Introduction: Pneumococcal infections cause a high death toll in Sub Saharan Africa (SSA) but the recently rolled out pneumococcal conjugate vaccines (PCV) will reduce the disease burden. To better understand the population impact of these vaccines, comprehensive analysis of large collections of pneumococcal isolates sampled prior to vaccination is required. Here we present a population genomic study of the invasive pneumococcal isolates sampled before the implementation of PCV13 in Malawi. Materials and methods: We retrospectively sampled and whole genome sequenced 585 invasive isolates from 2004 to 2010. We determine the pneumococcal population genetic structure and assessed serotype prevalence, antibiotic resistance rates, and the occurrence of serotype switching. Results: Population structure analysis revealed 22 genetically distinct sequence clusters (SCs), which consisted of closely related isolates. Serotype 1 (ST217), a vaccine-associated serotype in Glade SC2, showed highest prevalence (19.3%), and was associated with the highest MDR rate (81.9%) followed by serotype 12F, a non-vaccine-serotype in Glade SC10 with an MDR rate of 57.9%. Prevalence of serotypes was stable prior to vaccination although there was an increase in the PMEN19 clone, serotype 5 ST289, in Glade SC1 in 2010 suggesting a potential undetected local outbreak. Coalescent analysis revealed recent emergence of the SCs and there was evidence of natural capsule switching in the absence of vaccine induced selection pressure. Furthermore, majority of the highly prevalent capsule-switched isolates were associated with acquisition of vaccine-targeted capsules. Conclusions: This study provides descriptions of capsule-switched serotypes and serotypes with potential to cause serotype replacement post-vaccination such as 12F. Continued surveillance is critical to monitor these serotypes and antibiotic resistance in order to design better infection prevention and control measures such as inclusion of emerging replacement serotypes in future conjugate vaccines. (C) 2017 The Authors. Published by Elsevier Ltd.

Published
2017
Full Text
View/download PDF

24. Genomic landscape of extended-spectrum β-lactamase resistance in $\textit{Escherichia coli}$ from an urban African setting

Author

Musicha, P, Feasey, NA, Cain, AK, Kallonen, T, Chaguza, C, Peno, C, Khonga, M, Thompson, S, Gray, KJ, Mather, AE, Heyderman, RS, Everett, DB, Thomson, NR, Msefula, CL, and Apollo - University of Cambridge Repository

Subjects
Adult, Male, Malawi, Adolescent, Urban Population, Genetic Variation, Genomics, Microbial Sensitivity Tests, beta-Lactam Resistance, beta-Lactamases, Young Adult, Chloramphenicol, Genes, Bacterial, Child, Preschool, Drug Resistance, Multiple, Bacterial, Escherichia coli, Humans, Female, Child, Escherichia coli Infections, Phylogeny, Multilocus Sequence Typing
Abstract

$\textbf{Objectives}$: Efforts to treat $\textit{Escherichia coli}$ infections are increasingly being compromised by the rapid, global spread of antimicrobial resistance (AMR). Whilst AMR in E. coli has been extensively investigated in resource-rich settings, in sub-Saharan Africa molecular patterns of AMR are not well described. In this study, we have begun to explore the population structure and molecular determinants of AMR amongst $\textit{E. coli}$ isolates from Malawi. $\textbf{Methods}$: Ninety-four $\textit{E. coli}$ isolates from patients admitted to Queen's Hospital, Malawi, were whole-genome sequenced. The isolates were selected on the basis of diversity of phenotypic resistance profiles and clinical source of isolation (blood, CSF and rectal swab). Sequence data were analysed using comparative genomics and phylogenetics. $\textbf{Results}$: Our results revealed the presence of five clades, which were strongly associated with $\textit{E. coli}$ phylogroups A, B1, B2, D and F. We identified 43 multilocus STs, of which ST131 (14.9%) and ST12 (9.6%) were the most common. We identified 25 AMR genes. The most common ESBL gene was bla CTX-M-15 and it was present in all five phylogroups and 11 STs, and most commonly detected in ST391 (4/4 isolates), ST648 (3/3 isolates) and ST131 [3/14 (21.4%) isolates]. $\textbf{Conclusions}$: This study has revealed a high diversity of lineages associated with AMR, including ESBL and fluoroquinolone resistance, in Malawi. The data highlight the value of longitudinal bacteraemia surveillance coupled with detailed molecular epidemiology in all settings, including low-income settings, in describing the global epidemiology of ESBL resistance.

Published
2017

25. Prevalence of obesity, hypertension, and diabetes, and cascade of care in sub-Saharan Africa: a cross-sectional, population-based study in rural and urban Malawi

Author

Price, Alison J, Crampin, Amelia C, Amberbir, Alemayehu, Kayuni-Chihana, Ndoliwe, Musicha, Crispin, Tafatatha, Terence, Branson, Keith, Lawlor, Debbie A, Mwaiyeghele, Elenaus, Nkhwazi, Lawrence, Smeeth, Liam, Pearce, Neil, Munthali, Elizabeth, Mwagomba, Beatrice M, Mwansambo, Charles, Glynn, Judith R, Jaffar, Shabbar, and Nyirenda, Moffat

Abstract

Sub-Saharan Africa is in rapid demographic transition, and non-communicable diseases are increasingly important causes of morbidity and mortality. We investigated the burden of diabetes, overweight and obesity, hypertension, and multimorbidity, their treatment, and their associations with lifestyle and other factors in Malawi, a very poor country with a predominantly rural—but rapidly growing urban—population, to identify high-risk populations and inform appropriate interventions.

Published
2018
Full Text
View/download PDF

27. H3ABioNet, a sustainable pan-African bioinformatics network for human heredity and health in Africa

Author

Mulder, Nicola J., Adebiyi, Ezekiel, Alami, Raouf, Benkahla, Alia, Brandful, James, Doumbia, Seydou, Everett, Dean, Fadlelmola, Faisal M., Gaboun, Fatima, Gaseitsiwe, Simani, Ghazal, Hassan, Hazelhurst, Scott, Hide, Winston, Ibrahimi, Azeddine, Jaufeerally Fakim, Yasmina, Jongeneel, C. Victor, Joubert, Fourie, Kassim, Samar, Kayondo, Jonathan, Kumuthini, Judit, Lyantagaye, Sylvester, Makani, Julie, Mansour Alzohairy, Ahmed, Masiga, Daniel, Moussa, Ahmed, Nash, Oyekanmi, Ouwe Missi Oukem-Boyer, Odile, Owusu-Dabo, Ellis, Panji, Sumir, Patterton, Hugh, Radouani, Fouzia, Sadki, Khalid, Seghrouchni, Fouad, Tastan Bishop, Ozlem, Tiffin, Nicki, Ulenga, Nzovu, Adebiyi, Marion, Ahmed, Azza E., Ahmed, Rehab I., Alearts, Maaike, Alibi, Mohamed, Aron, Shaun, Baichoo, Shakuntala, Bendou, Hocine, Botha, Gerrit, Brown, David, Chimusa, Emile, Christoffels, Alan, Cornick, Jennifer, Entfellner, Jean-Baka Domelevo, Fields, Chris, Fischer, Anne, Gamieldien, Junaid, Ghedira, Kais, Ghouila, Amel, Sui, Shannan Ho, Isewon, Itunuoluwa, Isokpehi, Raphael, Dashti, Mahjoubeh Jalali Sefid, Kamng'ona, Arox, Khetani, Radhika S., Kiran, Anmol, Kulohoma, Benard, Kumwenda, Benjamin, Lapine, Dan, Mainzer, Liudmila Sergeevna, Maslamoney, Suresh, Mbiyavanga, Mamana, Meintjes, Ayton, Mlyango, Flora Elias, Mmbando, Bruno, Mohammed, Somia A., Mpangase, Phelelani, Msefula, Chisomo, Mtatiro, Siana Nkya, Mugutso, Dunfunk, Mungloo-Dilmohammud, Zahra, Musicha, Patrick, Nembaware, Victoria, Osamor, Victor Chukwudi, Oyelade, Jelili, Rendon, Gloria, Salazar, Gustavo A., Salifu, Samson Pandam, Sangeda, Raphael, Souiai, Oussema, Van Heusden, Peter, and Wele, Mamadou

Abstract

The application of genomics technologies to medicine and biomedical research is increasing in popularity, made possible by new high-throughput genotyping and sequencing technologies and improved data analysis capabilities. Some of the greatest genetic diversity among humans, animals, plants, and microbiota occurs in Africa, yet genomic research outputs from the continent are limited. The Human Heredity and Health in Africa (H3Africa) initiative was established to drive the development of genomic research for human health in Africa, and through recognition of the critical role of bioinformatics in this process, spurred the establishment of H3ABioNet, a pan-African bioinformatics network for H3Africa. The limitations in bioinformatics capacity on the continent have been a major contributory factor to the lack of notable outputs in high-throughput biology research. Although pockets of high-quality bioinformatics teams have existed previously, the majority of research institutions lack experienced faculty who can train and supervise bioinformatics students. H3ABioNet aims to address this dire need, specifically in the area of human genetics and genomics, but knock-on effects are ensuring this extends to other areas of bioinformatics. Here, we describe the emergence of genomics research and the development of bioinformatics in Africa through H3ABioNet.

Published
2016
Full Text
View/download PDF

28. Epidemiological and genomic landscape of antimicrobial resistance in Malawi

Author

Musicha, P, Everett, DB, Msefula, CL, and Feasey, NA

Abstract

Antimicrobial resistance (AMR) is a global public health problem, which presents a huge threat to the treatment of all forms of bacterial infections. A wide range of bacterial pathogens across the globe are increasingly developing resistance to multiple classes of antimicrobial agents rendering the agents concerned ineffective for the treatment of infections. Bloodstream infection (BSI) and other bacterial infections in sub-Saharan Africa (SSA) and Malawi in particular, are a common cause of morbidity and mortality. Few facilities in SSA however, are able to conduct long-term surveillance and as such the full burden of drug resistant infection (DRI) remain largely unknown across the region. In this thesis, blood cultures routinely taken from adult and paediatric medical patients admitted to Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi between 1998 and 2016 were analysed to describe trends in BSI and AMR. The analysis revealed a significant decline of BSI in all major pathogens except S. Typhi. However, the majority of isolates were resistant to the Malawian first-line antimicrobial agents (ampicillin, cotrimoxazole and chloramphenicol). Resistance to all the first line antimicrobial agents was more common in Gram-negative pathogens than Gram-positive pathogens. Non-Salmonellae Enterobacteriaceae that produced extended spectrum beta-lactamase (ESBL) and were fluoroquinolone-resistant were detected, and the proportions of these isolates rose significantly during the surveillance. In contrast, a majority of common Gram-positive pathogens remain susceptible to either penicillin or chloramphenicol. Methicillin resistant S. aureus was first reported in 1998 but became regularly detected in the later years of the surveillance. The analysis of blood culture isolates identified E. coli as one of the common causes of BSI in Blantyre, and the proportion of these isolates that were ESBL producers increased over time. Globally, efforts to treat E. coli infections are increasingly being compromised by the rapid, global spread of ESBL-producing E. coli. In this thesis, a whole genome sequencing (WGS) study was carried out to investigate the genetic population structure and molecular determinants of AMR in E. coli isolates from Malawi. Whole genomes of clinical E. coli isolates from patients admitted to QECH were sequenced and analysed using phylogenetic methods and comparative genomics. It was revealed that the E. coli population in Malawi is highly diverse with isolates belonging to five phylogroups, corresponding to five isolate sequence clusters (SCs) that contained over forty sequence types (STs). A unique sub-lineage of ST131 was identified that was distinct from previously defined sub-lineages of this globally disseminated ST. The most common ESBL gene was blaCT X-M-15. Unlike in other settings where presence of the blaCT X-M-15 gene was strongly linked to ST131, here the gene was not lineage-specific suggesting a distinct genomic landscape of ESBL-producing E. coli in Malawi. This thesis also identified Klebsiella spp. isolates as a common cause of BSI in Blantyre, and an increasing proportion of ESBL-producing and fluoroquinolone resistant isolates were identified. The molecular mechanisms and clones of K. pneumoniae associated with ESBL production and fluoroquinolone resistance were yet to be explored in Malawi. Here, a number of K. pneumoniae isolates were selected for WGS, and placed in a global context by comparison with previously sequenced K. pneumoniae isolates from multiple locations outside SSA, in order to identify the molecular determinants of AMR and determine their relationship with K. pneumoniae population structure. Genomic analysis revealed three main lineages of K. pneumoniae, which corresponded to the previously defined KpI, KpII and KpIII lineages. All three lineages exhibited high genetic diversity. Further phylogenetic analysis revealed a sub-lineage of KpI to be a major cause of CA infections in Malawi. The sub-lineage included the clonally related ST14 and ST15 of K. pneumoniae which cause hospital acquired infection in multiple settings across the globe, A large pool of AMR genes, was identified in the genomes of the Malawian isolates, including multiple ESBL and qnr genes. Plasmid-encoded CTX-M-15 was the most common type of ESBL that was identified. In common with E. coli from Malawi, AMR was not restricted to a particular clade of K. pneumoniae. These findings suggest that dissemination of AMR in the K. pneumoniae population in Malawi was either due to a combination of horizontal gene transfer and clonal expansion, or horizontal gene transfer alone. In conclusion, the thesis has shown that ESBL production and fluoroquinolone resistance is rapidly spreading in Malawi across multiple E. coli and K. pneumoniae lineages that are causing increasing levels of infection. As cephalosporins and fluoroquinolones remain the last resort antimicrobial agents in this setting, urgent action is needed to curb the spread of Gram-negative AMR pathogens.

29. H3ABioNet, a sustainable pan-African bioinformatics network for human heredity and health in Africa

Author

Samson Pandam Salifu, Radhika Khetani, Jelili Oyelade, Anmol Kiran, Cornelis Victor Jongeneel, Raphael Zozimus Sangeda, Kais Ghedira, Faisal M. Fadlelmola, Ayton Pierre Meintjes, Jen Cornick, Daniel Masiga, Khalid SADKI, Shakuntala Baichoo, Samar Kamal Kassim, Scott Hazelhurst, Azeddine Ibrahimi, Ozlem Tastan Bishop, Judit Kumuthini, Arox Wadson Kamng'ona, Rehab Ahmed, Nicola J Mulder, Dean Everett, Ahmed Moussa, Julie Makani, Chimusa Emile Rugamika, Jean-Baka Domelevo Entfellner, Phelelani Mpangase, Marion Adebiyi, Mohamed Alibi, Peter Van Heusden, Winston Hide, Victor Osamor, Hugh-George Patterton, Christopher Fields, Benjamin Kumwenda, Itunuoluwa Isewon, Souiai Oussama, Niklas Blomberg, Bruno Mmbando, Benard Kulohoma, Nicki Tiffin, Zahra Mungloo-Dilmohamud, Shaun Aron, Patrick Musicha, Stochastic Studies and Statistics, University of Cape Town, Department of Computer and Information Sciences, Covenant University, Centre National de Transfusion Sanguine, Rabat, Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP), Noguchi Memorial Institute for Medical Research [Accra, Ghana] (NMIMR), University of Ghana, University of Sciences, Techniques and Technology of Bamako, University of Liverpool, University of Khartoum, Institut National de Recherche Agronomique, Rabat, Botswana Harvard AIDS Institute Partnership, Université Mohammed Premier [Oujda], University of the Witwatersrand [Johannesburg] (WITS), University of Sheffield, Sheffield Institute for Translational Neuroscience, Department of Biotechnology Laboratory (Med-Biotech), Mohammed V University in Rabat, University of Mauritius, University of Illinois at Urbana-Champaign [Urbana], University of Illinois System, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt, Uganda Virus Research Institute, Entebbe, Uganda, Centre for Proteomic and Genomic Research, Cape Town, South Africa, University of Dar es Salaam, Dar es Salaam, Tanzania, Muhimbili University of Health and Allied Sciences, Zagazig University, International Centre of Insect Physiology and Ecology, Nairobi, Kenya, Institut de Chimie de Strasbourg, Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), National Biotechnology Development Agency, Abuja, Nigeria, Centre de Recherche Médicale et Sanitaire (Niamey, Niger) (CERMES), Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Department of Biomedical Sciences, University of Cape Town, Faculty of Health Sciences, University of the Free State [South Africa], Institut Pasteur du Maroc, Faculty of Sciences of Rabat, University Mohammed V of Rabat, Rabat, Morocco, Institut National d'Hygiène, Rabat, Morocco, Rhodes University, Grahamstown, University of the Western Cape, Cape Town, Management and Development for Health, Dar es Salaam, Tanzania, and Musicha, P

Subjects
Resource, 0301 basic medicine, Genetics, Medical, Genomic research, [SDV]Life Sciences [q-bio], Black People, Genomics, Health Promotion, Biology, MESH: Africa, SUSCEPTIBILITY, ANCESTRY, Bioinformatics, TUBERCULOSIS, DISEASE, 03 medical and health sciences, Human health, Computer Systems, Genetics, Humans, MESH: Genetics, Medical, MESH: Genetic Variation, GENOME-WIDE ASSOCIATION, Human heredity, Genetics (clinical), 2. Zero hunger, MESH: Humans, Pan african, MESH: Genomics, 1. No poverty, MESH: Computer Systems, Computational Biology, Genetic Variation, Popularity, Human genetics, 3. Good health, 030104 developmental biology, Health promotion, Africa, MESH: Health Promotion, MESH: African Continental Ancestry Group, MESH: Computational Biology
Abstract

International audience; The application of genomics technologies to medicine and biomedical research is increasing in popularity, made possible by new high-throughput genotyping and sequencing technologies and improved data analysis capabilities. Some of the greatest genetic diversity among humans, animals, plants, and microbiota occurs in Africa, yet genomic research outputs from the continent are limited. The Human Heredity and Health in Africa (H3Africa) initiative was established to drive the development of genomic research for human health in Africa, and through recognition of the critical role of bioinformatics in this process, spurred the establishment of H3ABioNet, a pan-African bioinformatics network for H3Africa. The limitations in bioinformatics capacity on the continent have been a major contributory factor to the lack of notable outputs in high-throughput biology research. Although pockets of high-quality bioinformatics teams have existed previously, the majority of research institutions lack experienced faculty who can train and supervise bioinformatics students. H3ABioNet aims to address this dire need, specifically in the area of human genetics and genomics, but knock-on effects are ensuring this extends to other areas of bioinformatics. Here, we describe the emergence of genomics research and the development of bioinformatics in Africa through H3ABioNet.

Published
2016
Full Text
View/download PDF

30. Salmonella carriage by geckos detected within households in Malawi.

Author

Wilson CN, Musicha P, Beale MA, Diness Y, Kanjerwa O, Salifu C, Katuah Z, Duncan P, Nyangu J, Mungu A, Deleza M, Banda L, Makhaza L, Elviss N, Jewell CP, Pinchbeck G, Thomson NR, Feasey NA, and Fèvre EM

Abstract

Salmonella was isolated from 23/79 (29.1%) pooled gecko stool samples from households in southern Malawi. Whole genome sequencing of 47 individual isolates within this collection revealed 27 Salmonella serovars spanning two subspecies. Our results demonstrate that geckos play an important role in the carriage of Salmonella within households., Competing Interests: None., (© 2024 Published by Elsevier B.V.)

Published
2024
Full Text
View/download PDF

31. Drivers of Resistance in Uganda and Malawi (DRUM): a protocol for the evaluation of One-Health drivers of Extended Spectrum Beta Lactamase (ESBL) resistance in Low-Middle Income Countries (LMICs).

Author

Cocker D, Sammarro M, Chidziwisano K, Elviss N, Jacob ST, Kajumbula H, Mugisha L, Musoke D, Musicha P, Roberts AP, Rowlingson B, Singer AC, Byrne RL, Edwards T, Lester R, Wilson CN, Hollihead B, Thomson NR, Jewell CP, Morse T, and Feasey NA

Abstract

In sub-Saharan Africa (sSA), there is high morbidity and mortality from severe bacterial infection and this is compounded by antimicrobial resistance, in particular, resistance to 3rd-generation cephalosporins. This resistance is typically mediated by extended-spectrum beta lactamases (ESBLs). To interrupt ESBL transmission it will be important to investigate how human behaviour, water, sanitation, and hygiene (WASH) practices, environmental contamination, and antibiotic usage in both urban and rural settings interact to contribute to transmission of ESBL E. coli and ESBL K. pneumoniae between humans, animals, and the environment. Here we present the protocol for the Drivers of Resistance in Uganda and Malawi (DRUM) Consortium, in which we will collect demographic, geospatial, clinical, animal husbandry and WASH data from a total of 400 households in Uganda and Malawi. Longitudinal human, animal and environmental sampling at each household will be used to isolate ESBL E. coli and ESBL K. pneumoniae. This will be complimented by a Risks, Attitudes, Norms, Abilities and Self-Regulation (RANAS) survey and structured observations to understand the contextual and psychosocial drivers of regional WASH practices. Bacterial isolates and plate sweeps will be further characterised using a mixture of short-,long-read and metagenomic whole-genome sequencing. These datasets will be integrated into agent-based models to describe the transmission of EBSL resistance in Uganda and Malawi and allow us to inform the design of interventions for interrupting transmission of ESBL-bacteria., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Cocker D et al.)

Published
2023
Full Text
View/download PDF

32. Evidence of widespread endemic populations of highly multidrug resistant Klebsiella pneumoniae in hospital settings in Hanoi, Vietnam: a prospective cohort study.

Author

Pham MH, Hoi LT, Beale MA, Khokhar FA, Hoa NT, Musicha P, Blackwell GA, Long HB, Huong DT, Binh NG, Co DX, Giang T, Bui C, Tran HN, Bryan J, Herrick A, Feltwell T, Nadjm B, Parkhill J, van Doorn HR, Trung NV, Van Kinh N, Török ME, and Thomson NR

Subjects
Humans, Vietnam epidemiology, Prospective Studies, Phylogeny, Tertiary Care Centers, Klebsiella pneumoniae genetics
Abstract

Background: Patients with prolonged hospitalisation have a significant risk of carriage of and subsequent infection with extended spectrum β-lactamase (ESBL)-producing and carbapenemase-producing Klebsiella pneumoniae. However, the distinctive roles of the community and hospital environments in the transmission of ESBL-producing or carbapenemase-producing K pneumoniae remain elusive. We aimed to investigate the prevalence and transmission of K pneumoniae within and between the two tertiary hospitals in Hanoi, Viet Nam, using whole-genome sequencing., Methods: We did a prospective cohort study of 69 patients in intensive care units (ICUs) from two hospitals in Hanoi, Viet Nam. Patients were included if they were aged 18 years or older, admitted for longer than the mean length of stay in their ICU, and cultured K pneumoniae from their clinical samples. Longitudinally collected samples from patients (collected weekly) and the ICU environment (collected monthly) were cultured on selective media, and whole-genome sequences from K pneumoniae colonies analysed. We did phylogenetic analyses and correlated phenotypic antimicrobial susceptibility testing with genotypic features of K pneumoniae isolates. We constructed transmission networks of patient samples, relating ICU admission times and locations with genetic similarity of infecting K pneumoniae., Findings: Between June 1, 2017, and Jan 31, 2018, 69 patients were in the ICUs and eligible for inclusion, and a total of 357 K pneumoniae isolates were cultured and successfully sequenced. 228 (64%) of K pneumoniae isolates carried between two and four different ESBL-encoding and carbapenemase-encoding genes, with 164 (46%) isolates carrying genes encoding both, with high minimum inhibitory concentrations. We found a novel co-occurrence of bla KPC-2 and bla NDM-1 in 46·6% of samples from the globally successful ST15 lineage. Despite being physically and clinically separated, the two hospitals shared closely related strains carrying the same array of antimicrobial resistance genes., Interpretation: These results highlight the high prevalence of ESBL-positive carbapenem-resistant K pneumoniae in ICUs in Viet Nam. Through studying K pneumoniae ST15 in detail, we showed how important resistance genes are contained within these strains that are carried broadly by patients entering the two hospitals directly or through referral., Funding: Medical Research Council Newton Fund, Ministry of Science and Technology, Wellcome Trust, Academy of Medical Sciences, Health Foundation, and National Institute for Health and Care Research Cambridge Biomedical Research Centre., Competing Interests: Declaration of interests JP is a paid consultant for Next Gen Diagnostics. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Published
2023
Full Text
View/download PDF

33. Effect of resistance to third-generation cephalosporins on morbidity and mortality from bloodstream infections in Blantyre, Malawi: a prospective cohort study.

Author

Lester R, Musicha P, Kawaza K, Langton J, Mango J, Mangochi H, Bakali W, Pearse O, Mallewa J, Denis B, Bilima S, Gordon SB, Lalloo DG, Jewell CP, and Feasey NA

Subjects
Humans, Escherichia coli, Prospective Studies, Malawi epidemiology, Anti-Bacterial Agents pharmacology, Cephalosporins pharmacology, Morbidity, Bacteremia drug therapy, Sepsis drug therapy
Abstract

Background: The burden of antimicrobial resistance is a major threat to global health; however, prospective clinical outcome data from Africa are scarce. In Malawi, third-generation cephalosporins are the antibiotics of choice in patients admitted to hospital despite a rapid proliferation of resistance to these drugs. We aimed to quantify the effect of resistance to third-generation cephalosporins on mortality and length of hospital stay among patients with bloodstream infections., Methods: We did a prospective cohort study of patients admitted to Queen Elizabeth Central Hospital in Blantyre, Malawi. Patients of all ages who had positive blood cultures for Enterobacterales were included, with the exception of those from the genus Salmonella, and were followed up for 180 days. We characterised blood culture isolates using whole-genome sequencing and used Cox regression models to estimate the effect of resistance to third-generation cephalosporins on length of hospital stay, in-hospital mortality, and survival., Findings: Between Jan 31, 2018, and Jan 13, 2020, we recruited 326 patients, from whom 220 (68%) of 326 isolates were resistant to third-generation cephalosporins. The case fatality proportion was 45% (99 of 220) in patients with bloodstream infections that were resistant to third-generation cephalosporins, and 34% (36 of 106) in patients with bloodstream infections that were sensitive to third-generation cephalosporins. Resistance to third-generation cephalosporins was associated with an increased probability of in-hospital mortality (hazard ratio [HR] 1·44, 95% CI 1·02-2·04), longer hospital stays (1·5 days, 1·0-2·0) and decreased probability of discharge alive (HR 0·31, 0·22-0·45). Whole-genome sequencing showed a high diversity of sequence types of both Escherichia coli and Klebsiella pneumoniae. Although isolates associated with death were distributed across clades, we identified three E coli clades (ST410, ST617, and ST648) that were isolated from 14 patients who all died., Interpretation: Resistance to third-generation cephalosporins is associated with increased mortality and longer hospital stays in patients with bloodstream infections in Malawi. These data show the urgent need for allocation of resources towards antimicrobial resistance mitigation strategies in Africa., Funding: Wellcome Trust and Wellcome Asia and Africa Programme., Competing Interests: Declaration of interests NAF received a Wellcome Asia and Africa Programme Grant to the Malawi Liverpool Wellcome Research Programme and a Medical Research Council programme grant. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Published
2022
Full Text
View/download PDF

34. Genomic investigation of a suspected Klebsiella pneumoniae outbreak in a neonatal care unit in sub-Saharan Africa.

Author

Cornick J, Musicha P, Peno C, Seager E, Iroh Tam PY, Bilima S, Bennett A, Kennedy N, Feasey N, Heinz E, and Cain AK

Subjects
Child, Disease Outbreaks, Genomics, Humans, Infant, Newborn, Malawi, Klebsiella Infections epidemiology, Klebsiella pneumoniae genetics
Abstract

A special-care neonatal unit from a large public hospital in Malawi was noted as having more frequent, difficult-to-treat infections, and a suspected outbreak of multi-drug-resistant Klebsiella pneumoniae was investigated using genomic characterisation. All K. pneumoniae bloodstream infections (BSIs) from patients in the neonatal ward ( n =62), and a subset of K. pneumoniae BSI isolates ( n =38) from other paediatric wards in the hospital, collected over a 4 year period were studied. After whole genome sequencing, the strain sequence types (STs), plasmid types, virulence and resistance genes were identified. One ST340 clone, part of clonal complex 258 (CC258) and an ST that drives hospital outbreaks worldwide, harbouring numerous resistance genes and plasmids, was implicated as the likely cause of the outbreak. This study contributes molecular information necessary for tracking and characterizing this important hospital pathogen in sub-Saharan Africa.

Published
2021
Full Text
View/download PDF

35. Duration of Carbapenemase-Producing Enterobacteriaceae Carriage in Hospital Patients.

Author

Mo Y, Hernandez-Koutoucheva A, Musicha P, Bertrand D, Lye D, Ng OT, Fenlon SN, Chen SL, Ling ML, Tang WY, Barkham T, Nagarajan N, Cooper BS, and Marimuthu K

Subjects
Bacterial Proteins genetics, Hospitals, Humans, beta-Lactamases genetics, Carbapenem-Resistant Enterobacteriaceae, Enterobacteriaceae Infections epidemiology
Abstract

To determine the duration of carbapenemase-producing Enterobacteriaceae (CPE) carriage, we studied 21 CPE carriers for »1 year. Mean carriage duration was 86 days; probability of decolonization in 1 year was 98.5%, suggesting that CPE-carriers' status can be reviewed yearly. Prolonged carriage was associated with use of antimicrobial drugs.

Published
2020
Full Text
View/download PDF

36. Early Signals of Vaccine-driven Perturbation Seen in Pneumococcal Carriage Population Genomic Data.

Author

Chaguza C, Heinsbroek E, Gladstone RA, Tafatatha T, Alaerts M, Peno C, Cornick JE, Musicha P, Bar-Zeev N, Kamng'ona A, Kadioglu A, McGee L, Hanage WP, Breiman RF, Heyderman RS, French N, Everett DB, and Bentley SD

Subjects
Carrier State epidemiology, Child, Humans, Infant, Malawi epidemiology, Nasopharynx, Pneumococcal Vaccines, Serogroup, Streptococcus pneumoniae genetics, Vaccines, Conjugate, Metagenomics, Pneumococcal Infections epidemiology, Pneumococcal Infections prevention & control
Abstract

Background: Pneumococcal conjugate vaccines (PCVs) have reduced pneumococcal diseases globally. Pneumococcal genomic surveys elucidate PCV effects on population structure but are rarely conducted in low-income settings despite the high disease burden., Methods: We undertook whole-genome sequencing (WGS) of 660 pneumococcal isolates collected through surveys from healthy carriers 2 years from 13-valent PCV (PCV13) introduction and 1 year after rollout in northern Malawi. We investigated changes in population structure, within-lineage serotype dynamics, serotype diversity, and frequency of antibiotic resistance (ABR) and accessory genes., Results: In children <5 years of age, frequency and diversity of vaccine serotypes (VTs) decreased significantly post-PCV, but no significant changes occurred in persons ≥5 years of age. Clearance of VT serotypes was consistent across different genetic backgrounds (lineages). There was an increase of nonvaccine serotypes (NVTs)-namely 7C, 15B/C, and 23A-in children <5 years of age, but 28F increased in both age groups. While carriage rates have been recently shown to remain stable post-PCV due to replacement serotypes, there was no change in diversity of NVTs. Additionally, frequency of intermediate-penicillin-resistant lineages decreased post-PCV. Although frequency of ABR genes remained stable, other accessory genes, especially those associated with mobile genetic element and bacteriocins, showed changes in frequency post-PCV., Conclusions: We demonstrate evidence of significant population restructuring post-PCV driven by decreasing frequency of vaccine serotypes and increasing frequency of few NVTs mainly in children under 5. Continued surveillance with WGS remains crucial to fully understand dynamics of the residual VTs and replacement NVT serotypes post-PCV., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Published
2020
Full Text
View/download PDF

37. Prevalence and outcome of bloodstream infections due to third-generation cephalosporin-resistant Enterobacteriaceae in sub-Saharan Africa: a systematic review.

Author

Lester R, Musicha P, van Ginneken N, Dramowski A, Hamer DH, Garner P, and Feasey NA

Subjects
Africa South of the Sahara epidemiology, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Cephalosporins pharmacology, Cephalosporins therapeutic use, Escherichia coli, Humans, Prevalence, Enterobacteriaceae Infections drug therapy, Enterobacteriaceae Infections epidemiology, Sepsis drug therapy
Abstract

Background: The prevalence of bacterial bloodstream infections (BSIs) in sub-Saharan Africa (sSA) is high and antimicrobial resistance is likely to increase mortality from these infections. Third-generation cephalosporin-resistant (3GC-R) Enterobacteriaceae are of particular concern, given the widespread reliance on ceftriaxone for management of sepsis in Africa., Objectives: Reviewing studies from sSA, we aimed to describe the prevalence of 3GC resistance in Escherichia coli, Klebsiella and Salmonella BSIs and the in-hospital mortality from 3GC-R BSIs., Methods: We systematically reviewed studies reporting 3GC susceptibility testing of E. coli, Klebsiella and Salmonella BSI. We searched PubMed and Scopus from January 1990 to September 2019 for primary data reporting 3GC susceptibility testing of Enterobacteriaceae associated with BSI in sSA and studies reporting mortality from 3GC-R BSI. 3GC-R was defined as phenotypic resistance to ceftriaxone, cefotaxime or ceftazidime. Outcomes were reported as median prevalence of 3GC resistance for each pathogen., Results: We identified 40 articles, including 7 reporting mortality. Median prevalence of 3GC resistance in E. coli was 18.4% (IQR 10.5 to 35.2) from 20 studies and in Klebsiella spp. was 54.4% (IQR 24.3 to 81.2) from 28 studies. Amongst non-typhoidal salmonellae, 3GC resistance was 1.9% (IQR 0 to 6.1) from 12 studies. A pooled mortality estimate was prohibited by heterogeneity., Conclusions: Levels of 3GC resistance amongst bloodstream Enterobacteriaceae in sSA are high, yet the mortality burden is unknown. The lack of clinical outcome data from drug-resistant infections in Africa represents a major knowledge gap and future work must link laboratory surveillance to clinical data., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Published
2020
Full Text
View/download PDF

38. Parallel evolution leading to impaired biofilm formation in invasive Salmonella strains.

Author

MacKenzie KD, Wang Y, Musicha P, Hansen EG, Palmer MB, Herman DJ, Feasey NA, and White AP

Subjects
Africa epidemiology, Biofilms growth & development, Child, Gastroenteritis epidemiology, Gastroenteritis microbiology, Humans, Phylogeny, Polymorphism, Single Nucleotide genetics, Salmonella Infections microbiology, Salmonella Infections transmission, Salmonella typhimurium pathogenicity, Trans-Activators genetics, Biological Evolution, Gastroenteritis genetics, Salmonella Infections genetics, Salmonella typhimurium genetics
Abstract

Pathogenic Salmonella strains that cause gastroenteritis are able to colonize and replicate within the intestines of multiple host species. In general, these strains have retained an ability to form the rdar morphotype, a resistant biofilm physiology hypothesized to be important for Salmonella transmission. In contrast, Salmonella strains that are host-adapted or even host-restricted like Salmonella enterica serovar Typhi, tend to cause systemic infections and have lost the ability to form the rdar morphotype. Here, we investigated the rdar morphotype and CsgD-regulated biofilm formation in two non-typhoidal Salmonella (NTS) strains that caused invasive disease in Malawian children, S. Typhimurium D23580 and S. Enteritidis D7795, and compared them to a panel of NTS strains associated with gastroenteritis, as well as S. Typhi strains. Sequence comparisons combined with luciferase reporter technology identified key SNPs in the promoter region of csgD that either shut off biofilm formation completely (D7795) or reduced transcription of this key biofilm regulator (D23580). Phylogenetic analysis showed that these SNPs are conserved throughout the African clades of invasive isolates, dating as far back as 80 years ago. S. Typhi isolates were negative for the rdar morphotype due to truncation of eight amino acids from the C-terminus of CsgD. We present new evidence in support of parallel evolution between lineages of nontyphoidal Salmonella associated with invasive disease in Africa and the archetypal host-restricted invasive serovar; S. Typhi. We hypothesize that the African invasive isolates are becoming human-adapted and 'niche specialized' with less reliance on environmental survival, as compared to gastroenteritis-causing isolates., Competing Interests: The authors have declared that no competing interests exist.

Published
2019
Full Text
View/download PDF

39. ChloS-HRM, a novel assay to identify chloramphenicol-susceptible Escherichia coli and Klebsiella pneumoniae in Malawi.

Author

Williams CT, Musicha P, Feasey NA, Adams ER, and Edwards T

Subjects
Escherichia coli classification, Escherichia coli genetics, Genes, Bacterial, Humans, Klebsiella pneumoniae classification, Klebsiella pneumoniae genetics, Malawi epidemiology, Public Health Surveillance, Sensitivity and Specificity, Chloramphenicol pharmacology, Escherichia coli drug effects, Escherichia coli Infections epidemiology, Escherichia coli Infections microbiology, Klebsiella Infections epidemiology, Klebsiella Infections microbiology, Klebsiella pneumoniae drug effects, Microbial Sensitivity Tests methods
Abstract

Objectives: Chloramphenicol is a broad-spectrum antimicrobial widely available in sub-Saharan Africa. With susceptibility re-emerging among Enterobacteriaceae in Blantyre, Malawi, we designed and evaluated a new high-resolution melt (HRM) RT-PCR assay, ChloS-HRM, to identify chloramphenicol-susceptible infections in a hospital setting., Methods: Seventy-two previously whole-genome sequenced isolates of Escherichia coli and Klebsiella pneumoniae from the Queen Elizabeth Central Hospital, Malawi, were subjected to determination of chloramphenicol MICs. Primers were designed to detect 18 chloramphenicol resistance genes that produce seven distinct peaks correlating with different gene groups (catA1, catA2, catA3, catB2, catB group 3, cmlA and floR) following HRM analysis. ChloS-HRM results were compared with MIC and WGS results., Results: ChloS-HRM correctly identified 15 of 17 phenotypically susceptible isolates and 54 of 55 resistant isolates, giving an accuracy of 88% in identifying susceptibility and 98% in identifying resistance. WGS identified 16 of 17 susceptible and 54 of 55 resistant isolates, giving an accuracy of 94% in identifying susceptibility and 98% in identifying resistance. The single false-susceptible result had no detectable gene by ChloS-HRM or WGS. Compared with WGS, ChloS-HRM had 100% sensitivity and specificity for catA (catA1-3), cmlA and floR, and 96% specificity for catB; sensitivity could not be estimated due to the lack of catB in the clinical sample collection. The overall agreement between MIC and HRM was 96% and between MIC and WGS it was 97%., Conclusions: ChloS-HRM could support antimicrobial stewardship in enabling de-escalation from third-generation cephalosporins by identifying chloramphenicol-susceptible infections. This would be valuable in areas with chloramphenicol-susceptible MDR and XDR Enterobacteriaceae., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Published
2019
Full Text
View/download PDF

40. Genomic analysis of Klebsiella pneumoniae isolates from Malawi reveals acquisition of multiple ESBL determinants across diverse lineages.

Author

Musicha P, Msefula CL, Mather AE, Chaguza C, Cain AK, Peno C, Kallonen T, Khonga M, Denis B, Gray KJ, Heyderman RS, Thomson NR, Everett DB, and Feasey NA

Subjects
Anti-Bacterial Agents pharmacology, Computational Biology methods, Drug Resistance, Multiple, Bacterial, Genetic Variation, Humans, Klebsiella pneumoniae isolation & purification, Malawi, Microbial Sensitivity Tests, Phylogeny, Genome, Bacterial, Genomics methods, Klebsiella Infections microbiology, Klebsiella pneumoniae classification, Klebsiella pneumoniae genetics, beta-Lactamases genetics
Abstract

Objectives: ESBL-producing Klebsiella pneumoniae (KPN) pose a major threat to human health globally. We carried out a WGS study to understand the genetic background of ESBL-producing KPN in Malawi and place them in the context of other global isolates., Methods: We sequenced genomes of 72 invasive and carriage KPN isolates collected from patients admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi. We performed phylogenetic and population structure analyses on these and previously published genomes from Kenya (n = 66) and from outside sub-Saharan Africa (n = 67). We screened for presence of antimicrobial resistance (AMR) genetic determinants and carried out association analyses by genomic sequence cluster, AMR phenotype and time., Results: Malawian isolates fit within the global population structure of KPN, clustering into the major lineages of KpI, KpII and KpIII. KpI isolates from Malawi were more related to those from Kenya, with both collections exhibiting more clonality than isolates from the rest of the world. We identified multiple ESBL genes, including blaCTX-M-15, several blaSHV, blaTEM-63 and blaOXA-10, and other AMR genes, across diverse lineages of the KPN isolates from Malawi. No carbapenem resistance genes were detected; however, we detected IncFII and IncFIB plasmids that were similar to the carbapenem resistance-associated plasmid pNDM-mar., Conclusions: There are multiple ESBL genes across diverse KPN lineages in Malawi and plasmids in circulation that are capable of carrying carbapenem resistance. Unless appropriate interventions are rapidly put in place, these may lead to a high burden of locally untreatable infection in vulnerable populations., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Published
2019
Full Text
View/download PDF

41. HIV-associated disruption of lung cytokine networks is incompletely restored in asymptomatic HIV-infected Malawian adults on antiretroviral therapy.

Author

Jambo KC, Tembo DL, Kamng'ona AW, Musicha P, Banda DH, Kankwatira AM, Malamba RD, Allain TJ, Heyderman RS, Russell DG, and Mwandumba HC

Abstract

Disruption of lung cytokine networks during chronic HIV infection is incompletely restored in individuals on antiretroviral therapy., Competing Interests: Conflict of interest: None declared.

Published
2017
Full Text
View/download PDF

42. Trends in antimicrobial resistance in bloodstream infection isolates at a large urban hospital in Malawi (1998-2016): a surveillance study.

Author

Musicha P, Cornick JE, Bar-Zeev N, French N, Masesa C, Denis B, Kennedy N, Mallewa J, Gordon MA, Msefula CL, Heyderman RS, Everett DB, and Feasey NA

Subjects
Adult, Child, Drug Resistance, Bacterial, Humans, Incidence, Malawi epidemiology, Population Surveillance, Retrospective Studies, Sepsis epidemiology, Time Factors, Anti-Bacterial Agents pharmacology, Bacteria drug effects, Hospitals, Sepsis microbiology
Abstract

Background: Bacterial bloodstream infection is a common cause of morbidity and mortality in sub-Saharan Africa, yet few facilities are able to maintain long-term surveillance. The Malawi-Liverpool-Wellcome Trust Clinical Research Programme has done sentinel surveillance of bacteraemia since 1998. We report long-term trends in bloodstream infection and antimicrobial resistance from this surveillance., Methods: In this surveillance study, we analysed blood cultures that were routinely taken from adult and paediatric patients with fever or suspicion of sepsis admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi from 1998 to 2016. The hospital served an urban population of 920 000 in 2016, with 1000 beds, although occupancy often exceeds capacity. The hospital admits about 10 000 adults and 30 000 children each year. Antimicrobial susceptibility tests were done by the disc diffusion method according to British Society of Antimicrobial Chemotherapy guidelines. We used the Cochran-Armitage test for trend to examine trends in rates of antimicrobial resistance, and negative binomial regression to examine trends in icidence of bloodstream infection over time., Findings: Between Jan 1, 1998, and Dec 31, 2016, we isolated 29 183 pathogens from 194 539 blood cultures. Pathogen detection decreased significantly from 327·1/100 000 in 1998 to 120·2/100 000 in 2016 (p<0·0001). 13 366 (51·1%) of 26 174 bacterial isolates were resistant to the Malawian first-line antibiotics amoxicillin or penicillin, chloramphenicol, and co-trimoxazole; 68·3% of Gram-negative and 6·6% of Gram-positive pathogens. The proportions of non-Salmonella Enterobacteriaceae with extended spectrum beta-lactamase (ESBL) or fluoroquinolone resistance rose significantly after 2003 to 61·9% in 2016 (p<0·0001). Between 2003 and 2016, ESBL resistance rose from 0·7% to 30·3% in Escherichia coli, from 11·8% to 90·5% in Klebsiella spp and from 30·4% to 71·9% in other Enterobacteriaceae. Similarly, resistance to ciprofloxacin rose from 2·5% to 31·1% in E coli, from 1·7% to 70·2% in Klebsiella spp and from 5·9% to 68·8% in other Enterobacteriaceae. By contrast, more than 92·0% of common Gram-positive pathogens remain susceptible to either penicillin or chloramphenicol. Meticillin-resistant Staphylococcus aureus (MRSA) was first reported in 1998 at 7·7% and represented 18·4% of S aureus isolates in 2016., Interpretation: The rapid expansion of ESBL and fluoroquinolone resistance among common Gram-negative pathogens, and the emergence of MRSA, highlight the growing challenge of bloodstream infections that are effectively impossible to treat in this resource-limited setting., Funding: Wellcome Trust, H3ABionet, Southern Africa Consortium for Research Excellence (SACORE)., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Published
2017
Full Text
View/download PDF

43. Genomic landscape of extended-spectrum β-lactamase resistance in Escherichia coli from an urban African setting.

Author

Musicha P, Feasey NA, Cain AK, Kallonen T, Chaguza C, Peno C, Khonga M, Thompson S, Gray KJ, Mather AE, Heyderman RS, Everett DB, Thomson NR, and Msefula CL

Subjects
Adolescent, Adult, Child, Child, Preschool, Chloramphenicol pharmacology, Escherichia coli isolation & purification, Escherichia coli Infections epidemiology, Female, Genes, Bacterial, Genetic Variation, Genomics, Humans, Malawi epidemiology, Male, Microbial Sensitivity Tests, Multilocus Sequence Typing, Phylogeny, Urban Population statistics & numerical data, Young Adult, Drug Resistance, Multiple, Bacterial genetics, Escherichia coli drug effects, Escherichia coli genetics, Escherichia coli Infections microbiology, beta-Lactam Resistance genetics, beta-Lactamases genetics
Abstract

Objectives: Efforts to treat Escherichia coli infections are increasingly being compromised by the rapid, global spread of antimicrobial resistance (AMR). Whilst AMR in E. coli has been extensively investigated in resource-rich settings, in sub-Saharan Africa molecular patterns of AMR are not well described. In this study, we have begun to explore the population structure and molecular determinants of AMR amongst E. coli isolates from Malawi., Methods: Ninety-four E. coli isolates from patients admitted to Queen's Hospital, Malawi, were whole-genome sequenced. The isolates were selected on the basis of diversity of phenotypic resistance profiles and clinical source of isolation (blood, CSF and rectal swab). Sequence data were analysed using comparative genomics and phylogenetics., Results: Our results revealed the presence of five clades, which were strongly associated with E. coli phylogroups A, B1, B2, D and F. We identified 43 multilocus STs, of which ST131 (14.9%) and ST12 (9.6%) were the most common. We identified 25 AMR genes. The most common ESBL gene was bla CTX-M-15 and it was present in all five phylogroups and 11 STs, and most commonly detected in ST391 (4/4 isolates), ST648 (3/3 isolates) and ST131 [3/14 (21.4%) isolates]., Conclusions: This study has revealed a high diversity of lineages associated with AMR, including ESBL and fluoroquinolone resistance, in Malawi. The data highlight the value of longitudinal bacteraemia surveillance coupled with detailed molecular epidemiology in all settings, including low-income settings, in describing the global epidemiology of ESBL resistance., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results