Research Articles (Medical Microbiology)

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The emerging concern of IMP variants being resistant to the only IMP-type metallo-β-lactamase inhibitor, xeruborbactam
(American Society for Microbiology, 2025-07) Le Terrier, Christophe; Drusin, Salvador I.; Nordmann, Patrice; Pitout, Johann D.D.; Peirano, Gisele; Vila, Alejandro J.; Moreno, Diego M.; Poirel, Laurent
Metallo-β-lactamases (MBLs) of IMP type are not inhibited by currently commercialized β-lactamase inhibitors, including taniborbactam (TAN), which inhibits only NDM- and VIM-type enzymes. However, the development of xeruborbactam (XER), which additionally inhibits IMP enzymes, may provide effective drug combinations such as meropenem-XER (MEM-XER) against most MBL producers. Thirty-two IMP-producing clinical gram-negative isolates were tested for MEM-XER. Susceptibility testing of β-lactams with TAN or XER at 4 or 8 µg/mL was performed. Noticeably, MEM-XER remained ineffective against all IMP-producing Pseudomonas aeruginosa isolates. By contrast, supplementation with XER significantly lowered MEM MICs for several IMP-producing Enterobacterales isolates, except for isolates and recombinant E. coli strains producing IMP-6, IMP-10, IMP-14, and IMP-26. Interestingly, IMP-59 producers showed susceptibility to both TAN- and XER-based combinations, although IMP enzymes are not supposed to be inhibited by TAN. Determinations of 50% inhibitory concentration (IC50) values of XER showed values being >15-fold higher for IMP-6, IMP-10, IMP-14, and IMP-26 compared with IMP-1. Interestingly, the IC50 value of TAN for IMP-59 was found in the same range as that for NDM-1 (7 µM). Finally, structural analyses and molecular modeling simulations indicated that the Ser262Gly mutation in IMP-6 may alter the electronic properties of the active site, whereas the Phe residue in IMP-10 may exert a steric effect counteracting XER binding. Resistance to XER in IMP-6, IMP-10, IMP-14, and IMP-26 variants, conferring resistance to MEM-XER, might be considered a serious concern since MEM-XER will be supposed to be a salvage therapy for MBL-, and especially IMP-producing Enterobacterales infections.
Static vs. cidal : it's not complex; it's simply incorrect
(American Society for Microbiology, 2025-08) Spellberg, Brad; Wald-Dickler, Noah; Holtom, Paul; Meyer-Sautter, Pascal; Camp, Austin; Diaz, Alejandro Diaz; Buhamad, Ranya; Vazquez, Ali Sebastian Meza; Aguirre-Garcia, Gloria Mayela; Stanton, Matthew; Butler-Wu, Susan M.; Chiu, Isabelle; Ergenc, Zeynep; Bhoojhawon, Guru; Murri, Rita; Maraolo, Alberto Enrico; Cabanilla, Gabriela; Riccardi, Niccolo; Tshisevhe, Vhudzani; Behenna, Curtis; Williams, Karen S.; Kufel, Wesley D.; Wojciaczyk, Natalia; Pimentel, Bernardo Vidal; Muyidi, Ahmed; Costa, Rodrigo P.L.; Motta, Fabrizio; Bortolussi-Courval, Emilie; Lee, Todd C.; Mcdonald, Emily; Ghanem, Bassam; Nelson, Zachary
No abstract available.
Global, regional, and national age-specific progress towards the 2020 milestones of the WHO End TB Strategy : a systematic analysis for the Global Burden of Disease Study 2021
(Elsevier, 2024-07) Ledesma, Jorge R.; Ma, Jianing; Zhang, Meixin; Basting, Ann V.L.; Chu, Huong Thi; Vongpradith, Avina; Novotney, Amanda; LeGrand, Kate E.; Xu, Yvonne Yiru; Dai, Xiaochen; Nicholson, Sneha Ingle; Stafford, Lauryn K.; Carter, Austin; Ross, Jennifer M; Abbastabar, Hedayat; Richard Gyan , Meriem; Abdulah, Deldar Morad; Aboagye, Richard Gyan; Abolhassani, Hassan; Abrha, Woldu Aberhe; Abubaker Ali, Hiwa; Abu-Gharbieh, Eman; Aburuz, Salahdein; Addo, Isaac Yeboah; Adepoju, Abiola Victor; Adhikari, Kishor; Adnani, Qorinah Estiningtyas Sakilah; Adra, Saryia; Afework, Abel; Aghamiri, Shahin; Agyemang-Duah, Williams; Ahinkorah, Bright Opoku; Ahmad, Danish; Ahmad, Sajjad; Ahmadzade, Amir Mahmoud; Ahmed, Haroon; Ahmed, Mohammed; Ahmed, Ayman; Akinosoglou, Karolina; AL-Ahdal, Tareq Mohammed Ali; Alam, Nazmul; Albashtawy, Mohammed; AlBataineh, Mohammad T.; Al-Gheethi, Adel Ali Saeed; Ali, Abid; Ali, Endale Alemayehu; Ali, Liaqat; Ali, Zahid; Ali, Syed Shujait Shujait; Allel, Kasim; Altaf, Awais; Al-Tawfiq, Jaffar A.; Alvis-Guzman, Nelson; Alvis-Zakzuk, Nelson J.; Amani, Reza; Amusa, Ganiyu Adeniyi; Amzat , Jimoh; Andrews, Jason R.; Anil, Abhishek; Anwer, Razique; Aravkin, Aleksandr Y; Areda, Damelash; Artamonov, Anton A.; Aruleba, Raphael Taiwo; Asemahagn, Mulusew A.; Atre, Sachin R.; Aujayeb, Avinash; Azadi, Davood; Azadnajafabad, Sina; Azzam, Ahmed Y.; Badar, Muhammad; Badiye, Ashish D.; Bagherieh, Sara; Bahadorikhalili, Saeed; Baig, Atif Amin; Banach, Maciej; Banik, Biswajit; Bardhan, Mainak; Barqawi, Hiba Jawdat; Basharat, Zarrin; Baskaran, Pritish; Basu, Saurav; Beiranvand, Maryam; Belete, Melaku Ashagrie; Belew, Makda Abate; Belgaumi, Uzma Iqbal; Beloukas, Apostolos; Bettencourt, Paulo J G; Bhagavathula,, Akshaya Srikanth; Bhardwaj, Nikha; Bhardwaj, Pankaj; Bhargava, Ashish; Bhat, Vivek; Bhatti, Jasvinder Singh; Bhatti, Gurjit Kaur; Bikbov, Boris; Bitra, Veera R.; Bjegovic-Mikanovic, Vesna; Buonsenso, Danilo; Burkart, Katrin; Bustanji, Yasser; Butt, Zahid A.; Camargos, Paulo; Cao, Yu; Carr, Sinclair; Carvalho, Felix; Cegolon, Luca; Cenderadewi, Muthia; Cevik, Muge; Chahine, Yaacoub; Chattu, Vijay Kumar; Ching, Patrick R.; Chopra, Hitesh; Chung, Eunice; Claassens, Mareli M.; Coberly, Kaleb; Cruz-Martins, Natália; Dabo, Bashir; Dadana, Sriharsha; Dadras, Omid; Darban, Isaac; Darega Gela, Jiregna; Darwesh, Aso Mohammad; Dashti, Mahmood; Demessa, Berecha Hundessa; Demisse, Biniyam; Demissie, Solomon; Derese, Awoke Masrie Asrat; Deribe, Kebede; Desai, Hardik Dineshbhai; Devanbu, Vinoth Gnana Chellaiyan; Dhali, Arkadeep; Dhama, Kuldeep; Dhingra, Sameer; Do, Thao Huynh Phuong; Dongarwar, Deepa; Dsouza, Haneil Larson; Dube, John; Dziedzic, Arkadiusz Marian; Ed-Dra, Abdelaziz; Efendi, Ferry; Effendi, Diyan Ermawan; Eftekharimehrabad, Aziz; Ekadinata, Nopryan; Ekundayo, Temitope Cyrus; Elhadi, Muhammed; Elilo, Legesse Tesfaye; Emeto, Theophilus I.; Engelbert Bain, Luchuo; Fagbamigbe, Adeniyi Francis; Fahim, Ayesha; Feizkhah, Alireza; Fetensa, Getahun; Fischer, Florian; Gaipov, Abduzhappar; Gandhi, , , Aravind P.; Gautam, Rupesh K.; Gebregergis, Miglas W.; Gebrehiwot, Mesfin; Gebrekidan, Kahsu Gebrekirstos; Ghaffari, Kazem; Ghassemi, Fariba; Ghazy, Ramy Mohamed; Goodridge, Amador; Goyal, Anmol; Guan, Shi-Yang; Gudeta, Mesay Dechasa; Guled, Rashid Abdi; Gultom, Novianti Br; Gupta, Veer Bala; Gupta, Vivek Kumar; Gupta, Sapna; Hagins, Hailey; Hailu, Semira Goitom; Hailu, Wase Benti; Hamidi, Samer; Hanif, Asif; Harapan, Harapan; Hasan, Rumina Syeda; Hassan, Shoaib; Haubold, Johannes; Hezam, Kamal; Hong, Sung Hwi; Horita, Nobuyuki; Hossain, Md Belal; Hosseinzadeh, Mehdi; Hostiuc, Mihaela; Hostiuc, Sorin; Huynh , Hong-Han; Ibitoye, Segun Emmanuel; Ikuta, Kevin S.; Ilic, Irena M.; Ilic, Milena D; Islam, Md Rabiul; Ismail, Nahlah Elkudssiah; Ismail, Faisal; Jafarzadeh, Abdollah; Jakovljevic, Mihajlo; Jalili, Mahsa; Janodia, Manthan Dilikumar; Jomehzadeh, Nabi; Jonas, Jost B.; Joseph, Nitin; Joshua, Charity Ehimwenma; Kabir, Zubair; Kamble, Bhushan Dattatray; Kanchan, Tanuj; Kandel, Himal; Kanmodi, Kehinde Kazeem; Kantar, Rami S.; Karaye, Ibraheem M.; Karimi Behnagh, Arman; Kassa, Gebrehiwot G.; Kaur, Rimple Jeet; Kaur, Navjot; Khajuria, Himanshu; Khamesipour , Faham; Khan, Yusra H.; Khan, M. Nuruzzaman; Khan Suheb, Mahammed Ziauddin; Khatab, Khaled; Khatami, Fatemeh; Kim, Min Seo; Kosen, Soewarta; Koul, Parvaiz A.; Koulmane Laxminarayana, Sindhura Lakshmi; Krishan, Kewal; Kucuk Bicer, Burcu; Kuddus, Md Abdul; Kulimbet, Mukhtar; Kumar, Nithin; Kumar Lal, Dharmesh; Landires, Iván; Latief, Kamaluddin; Le, Trang Diep Thanh; Le, Thao Thi Thu; Ledda , Caterina; Lee, Munjae; Lee, Seung Won; Lerango, Temesgen L.; Lim, Stephen S.; Liu, Chaojie; Liu, Xuefeng; Lopukhov, Platon D.; Luo, Hong; Lv, Hengliang; Mahajan, Preetam Bhalchandra; Mahboobipour, Ali; Majeed, Azeem; Malakan Rad, Elaheh; Malhotra, Kashish; Malik, Muhammad Sajeel Ahmed; Malinga, Lesibana Anthony; Mallhi, Tauqeer Hussain; Manilal, Aseer; Martinez-Guerra , Bernardo Alfonso; Martins-Melo, Francisco Rogerlândio; Marzo, Roy Rillera; Masoumi-Asl, Hossein; Mathur, Vasundhara; Maude, Richard James; Mehrotra, Ravi; Memish, Ziad A.; Mendoza, Walter; Menezes, Ritesh G.; Merza, Muayad Aghali; Mestrovic, Tomislav; Mhlanga, Laurette; Misra, Sanjeev; Misra, Arup Kumar; Mithra, Prasanna; Moazen, Babak; Mohammed, Hussen; Mokdad, Ali H.; Monasta, Lorenzo; Moore, Catrin E.; Mousavi, Parsa; Mulita, Francesk; Musaigwa, Fungai; Muthusamy, Raman; Naghavi, Ahamarshan Jayaraman; Naik, Pirouz; Naik, Ganesh R.; Naik, Gurudatta; Nair, Sanjeev; Nair, Tapas Sadasivan; Natto, Zuhair S.; Nayak, Biswa Prakash; Negash, Hadush; Nguyen, Dang H.; Nguyen, Van Thanh; Niazi, Robina Khan; Nnaji, Chukwudi A.; Nnyanzi, Lawrence Achilles; Noman, Efaq Ali; Nomura, Shuhei; Oancea, Bogdan; Obamiro, Kehinde O.; Odetokun, Ismail A.; Odo Odo, Daniel Bogale; Odukoya, Oluwakemi Ololade; Oh, In-Hwan; Okereke, Chukwuma O.; Okonji, Osaretin Christabel; Oren, Eyal; Ortiz-Brizuela, Edgar; Osuagwu, Uchechukwu Levi; Ouyahia, Amel; P A, Mahesh Padukudru; Parija, Pragyan Paramita; Parikh, Romil R.; Park, Seoyeon; Parthasarathi, Ashwaghosha; Patil, Shankargouda; Pawar, Shrikant; Peng, Minjin; Pepito, Veincent Christian Filipino; Peprah, Prince; Perdigão, João; Perico, Norberto; Pham, Hoang Tran; Postma, Maarten J.; Prabhu, Attur Ravindra Attur; Prasad, Manya; Prashant, Akila; Prates, Elton Junio Sady; Rahim, Fakher; Rahman, Mosiur; Rahman, Muhammad Aziz; Rahmati, Masoud; Rajaa, Sathish; Ramasamy, Shakthi Kumaran; Rao, Indu Ramachandra; Rao, Sowmya J.; Rapaka, Deepthi; Rashid, Ahmed Mustafa; Ratan, Zubair Ahmed; Ravikumar, Nakul; Rawaf, Salman; Reddy, Murali Mohan Rama Krishna; Redwan, Elrashdy Moustafa Mohamed; Remuzzi, Giuseppe; Reyes, Luis Felipe; Rezaei, Nazila; Rezaeian, Mohsen; Rezahosseini, Omid; Rodrigues, Mónica; Roy, Priyanka; Ruela , Guilherme de Andrade; Sabour, Siamak; Saddik, Basema; Saeed, Umar; Safi, Sher Zaman; Saheb Sharif-Askari , Narjes; Saheb Sharif-Askari , Fatemeh; Sahebkar, Amirhossein; Sahiledengle, Biniyam; Sahoo, Soumya Swaroop; Salam, Nasir; Salami, Afeez Abolarinwa; Saleem, Samreen; Saleh, Mohamed A.; Samadi Kafil, Hossein; Samadzadeh, Sara; Samodra, Yoseph Leonardo; Sanjeev, Rama Krishna; Saravanan, Aswini; Sawyer, Susan M.; Selvaraj, Siddharthan; Senapati, Sabyasachi; Senthilkumaran, Subramanian; Shah, Pritik A.; Shahid, Samiah; Shaikh, Masood Ali; Sham, Sunder; Shamshirgaran, Mohammad Ali; Shanawaz, Mohd; Sharath, Medha; Sherchan, Samendra P.; Shetty, Ranjitha S.; Shirzad-Aski, Hesamaddin; Shittu, Aminu; Siddig, Emmanuel Edwar; Silva, João Pedro; Singh, Surjit; Singh, Paramdeep; Singh, Harpreet; Singh, Jasvinder A.; Siraj, Md Shahjahan; Siswanto, Siswanto; Solanki, Ranjan; Solomon, Yonatan; Joan B.; Sreeramareddy, Chandrashekhar T.; Srivastava, Vijay Kumar; Steiropoulos, Paschalis; Swain, Chandan Kumar; Tabuchi, Takahiro; Tampa, Mircea; Jacques J.L. Lukenze, Tamuzi; Tat, Nathan Y.; Tavakoli Oliaee, Razieh; Teklay, Gebrehiwot; Tesfaye, Edosa Geta; Tessema, Belay; Thangaraju, Pugazhenthan; Thapar, Rekha; Thum, Chern Choong Chern; Ticoalu, Jansje Henny Vera; Tleyjeh, Imad M.; Tobe-Gai, Ruoyan; Toma, Temesgen Mohammed; Tram, Khai Hoan; Udoakang, Aniefiok John; Umar, , , , , , , , Tungki Pratama; Umeokonkwo, Chukwuma David; Vahabi, Seyed Mohammad; Vaithinathan, Asokan Govindaraj; Van Boven, Job F.M.; Varthya, Shoban Babu; Wang, Ziyue; Warsame, Muktar S.A.; Westerman, Ronny; Wonde, Tewodros Eshete; Yaghoubi, Sajad; Yi, Siyan; Yiğit, Vahit; Yon, Dong Keon; Yonemoto, Naohiro; Yu, Chuanhua; Zakham, Fathiah; Zangiabadian, Moein; Zeukeng, Francis; Zhang , Haijun; Zhao, Yang; Zheng, Peng; Zielińska, Magdalena; Salomon, Joshua A.; Reiner Jr, Robert C.; Naghavi, Mohsen; Vos, Theo; Hay, Simon I.; Murray, Christopher J.L.; Kyu, Hmwe Hmwe; Soriano, Joan B.; Atre; Aujayeb; Azadi; Azadnajafabad; Sina
BACKGROUND : Global evaluations of the progress towards the WHO End TB Strategy 2020 interim milestones on mortality (35% reduction) and incidence (20% reduction) have not been age specific. We aimed to assess global, regional, and national-level burdens of and trends in tuberculosis and its risk factors across five separate age groups, from 1990 to 2021, and to report on age-specific progress between 2015 and 2020. METHODS : We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021) analytical framework to compute age-specific tuberculosis mortality and incidence estimates for 204 countries and territories (1990-2021 inclusive). We quantified tuberculosis mortality among individuals without HIV co-infection using 22 603 site-years of vital registration data, 1718 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, 680 site-years of mortality surveillance data, and 9 site-years of minimally invasive tissue sample (MITS) diagnoses data as inputs into the Cause of Death Ensemble modelling platform. Age-specific HIV and tuberculosis deaths were established with a population attributable fraction approach. We analysed all available population-based data sources, including prevalence surveys, annual case notifications, tuberculin surveys, and tuberculosis mortality, in DisMod-MR 2.1 to produce internally consistent age-specific estimates of tuberculosis incidence, prevalence, and mortality. We also estimated age-specific tuberculosis mortality without HIV co-infection that is attributable to the independent and combined effects of three risk factors (smoking, alcohol use, and diabetes). As a secondary analysis, we examined the potential impact of the COVID-19 pandemic on tuberculosis mortality without HIV co-infection by comparing expected tuberculosis deaths, modelled with trends in tuberculosis deaths from 2015 to 2019 in vital registration data, with observed tuberculosis deaths in 2020 and 2021 for countries with available cause-specific mortality data. FINDINGDS : We estimated 9·40 million (95% uncertainty interval [UI] 8·36 to 10·5) tuberculosis incident cases and 1·35 million (1·23 to 1·52) deaths due to tuberculosis in 2021. At the global level, the all-age tuberculosis incidence rate declined by 6·26% (5·27 to 7·25) between 2015 and 2020 (the WHO End TB strategy evaluation period). 15 of 204 countries achieved a 20% decrease in all-age tuberculosis incidence between 2015 and 2020, eight of which were in western sub-Saharan Africa. When stratified by age, global tuberculosis incidence rates decreased by 16·5% (14·8 to 18·4) in children younger than 5 years, 16·2% (14·2 to 17·9) in those aged 5-14 years, 6·29% (5·05 to 7·70) in those aged 15-49 years, 5·72% (4·02 to 7·39) in those aged 50-69 years, and 8·48% (6·74 to 10·4) in those aged 70 years and older, from 2015 to 2020. Global tuberculosis deaths decreased by 11·9% (5·77 to 17·0) from 2015 to 2020. 17 countries attained a 35% reduction in deaths due to tuberculosis between 2015 and 2020, most of which were in eastern Europe (six countries) and central Europe (four countries). There was variable progress by age: a 35·3% (26·7 to 41·7) decrease in tuberculosis deaths in children younger than 5 years, a 29·5% (25·5 to 34·1) decrease in those aged 5-14 years, a 15·2% (10·0 to 20·2) decrease in those aged 15-49 years, a 7·97% (0·472 to 14·1) decrease in those aged 50-69 years, and a 3·29% (-5·56 to 9·07) decrease in those aged 70 years and older. Removing the combined effects of the three attributable risk factors would have reduced the number of all-age tuberculosis deaths from 1·39 million (1·28 to 1·54) to 1·00 million (0·703 to 1·23) in 2020, representing a 36·5% (21·5 to 54·8) reduction in tuberculosis deaths compared to those observed in 2015. 41 countries were included in our analysis of the impact of the COVID-19 pandemic on tuberculosis deaths without HIV co-infection in 2020, and 20 countries were included in the analysis for 2021. In 2020, 50 900 (95% CI 49 700 to 52 400) deaths were expected across all ages, compared to an observed 45 500 deaths, corresponding to 5340 (4070 to 6920) fewer deaths; in 2021, 39 600 (38 300 to 41 100) deaths were expected across all ages compared to an observed 39 000 deaths, corresponding to 657 (-713 to 2180) fewer deaths. INTERPRETATION : Despite accelerated progress in reducing the global burden of tuberculosis in the past decade, the world did not attain the first interim milestones of the WHO End TB Strategy in 2020. The pace of decline has been unequal with respect to age, with older adults (ie, those aged >50 years) having the slowest progress. As countries refine their national tuberculosis programmes and recalibrate for achieving the 2035 targets, they could consider learning from the strategies of countries that achieved the 2020 milestones, as well as consider targeted interventions to improve outcomes in older age groups.
Enterobacterales use capsules, transporters, mobile genetic elements, and other evolutionary adaptations to survive antibiotics exposure in the absence of resistance genes
(Taylor and Francis, 2025-12) Mmatli, Masego; Mbelle, Nontombi Marylucy; Fourie, Bernard P.; Osei Sekyere, John; j.oseisekyere@up.ac.za
Carbapenems and colistin are last-resort antibiotics used to manage difficult-to-treat infections caused by Gram-negative bacteria. However, resistance to these two antibiotics is rising globally, and there is limited knowledge on how pathogens evolve resistance when known resistance genes are absent. METHODS : Whole-genome sequencing, transcriptomic profiling, and epigenomic analyses were performed. Phenotypic assays were used to evaluate the effects of various inhibitors on antibiotic susceptibility, while bioinformatic pipelines were used to characterize resistance determinants, virulence factors, and mobile genetic elements (MGEs). RESULTS : Phylogenetic analysis revealed widespread carriage of diverse resistance genes, particularly on plasmids of K. pneumoniae, while Enterobacter species possessed fewer known ARGs. Despite lacking known carbapenemase and mcr genes, several isolates demonstrated colistin or carbapenem resistance mediated by upregulation of efflux pumps, overproduction of capsular polysaccharides, mutations in outer membrane proteins, and potential lipopolysaccharide-modifying enzymes. Transcriptomic analysis revealed significant differential gene expression upon antibiotic exposure. Notably, genes encoding ABC transporter proteins were significantly downregulated (p-value <0.0001, fold change > 10), while genes encoding transposases were significantly upregulated (p-value <0.0001, fold change > 11). These changes underscore the critical role of transporters and MGEs in antibiotic resistance adaptation. CONCLUSIONS : In the absence of canonical carbapenemase and mcr genes, K. pneumoniae and Enterobacter species can deploy a spectrum of adaptive mechanisms, including efflux pumps, mobile elements, and altered outer membrane/capsule structures, to overcome colistin and carbapenem treatments. These findings support the need for ongoing surveillance of novel or underrecognized resistance mechanisms to preserve the efficacy of last-line antibiotics.
Recommendations for the optimal introduction of novel antibiotics to treat uncomplicated gonorrhoea in the face of increasing antimicrobial resistance : a case study with zoliflodacin
(BioMed Central, 2024-09-03) Pascual, Fernando; Au, Carmen; Chikwari, Chido Dziva; Daram, Pierre; Deal, Carolyn; Miranda, Angelica Espinosa; Grad, Yonatan H.; Hook, Edward WIII; Kittiyaowamarn, Rossaphorn; Luckey, Alison; Low, Nicola; Maseko, Venessa; Peters, Remco P.H.; Roberts, Teri; Unemo, Magnus; Srinivasan, Subasree
New, first-in-class oral antibiotics like zoliflodacin, developed in a public–private partnership, require an optimal introduction strategy while ensuring antibiotic stewardship. Zoliflodacin, given as a single dose for uncomplicated urogenital gonorrhoea, recently demonstrated non-inferiority to ceftriaxone plus azithromycin and safety in a phase 3 randomised controlled trial. Following regulatory approval, zoliflodacin could improve sexually transmitted infection (STI) management and help address the threat of untreatable gonorrhoea, as levels of resistance to current first-line treatments increase. The Global Antibiotic Research & Development Partnership (GARDP) convened an expert meeting during the 2023 STI and HIV World Congress to discuss key questions about the introduction of zoliflodacin in low- and middle-income countries (LMICs). The questions included: which patients to treat in which situations, the timing of introduction, and what additional evidence is needed to change policy for the use of new antibiotics for gonorrhoea. Recommendations from the expert group included: the generation of evidence for the role of a drug like zoliflodacin in clinical treatment failures; the need for additional antimicrobial resistance surveillance; investigation of the role of novel diagnostic approaches, such as point-of-care tests, to improve stewardship; study of preferences and values among the population in need; and modelling of the emergence of N. gonorrhoeae resistance and transmission in different scenarios. Forthcoming World Health Organization (WHO) global guidelines could outline recommendations for a new oral antibiotic like zoliflodacin based on existing evidence, and rational approaches for certain populations or use cases, while the evidence base is further strengthened.
Tobacco smoking clusters in households affected by tuberculosis in an individual participant data meta-analysis of national tuberculosis prevalence surveys : time for household-wide interventions?
(Public Library of Science, 2024-02-29) Hamada, Yohhei; Quartagno, Matteo; Law, Irwin; Malik, Farihah; Bonsu, Frank Adae; Adetifa, Ifedayo M. O.; Adusi-Poku, Yaw; D’Alessandro, Umberto; Bashorun, Adedapo Olufemi; Begum, Vikarunnessa; Lolong, Dina Bisara; Boldoo, Tsolmon; Dlamini, Themba; Donkor, Simon; Dwihardiani, Bintari; Egwaga, Saidi; Farid, Muhammad N.; Garfin, Anna Marie Celina G.; Donna Mae G., Gaviola; Husain, Mohammad Mushtuq; Ismail, Farzana; Kaggwa, Mugagga; Kamara, Deus V.; Kasozi, Samuel; Kaswaswa, Kruger; Kirenga, Bruce; Klinkenberg, Eveline; Kondo, Zuweina; Lawanson, Adebola; Macheque, David; Manhica, Ivan; Maama-Maime, Llang Bridget; Mfinanga, Sayoki; Moyo, Sizulu; Mpunga, James; Mthiyane, Thuli; Mustikawati, Dyah Erti; Mvusi, Lindiwe; Nguyen, Hoa Binh; Nguyen, Hai Viet; Pangaribuan, Lamria; Patrobas, Philip; Rahman, Mahmudur; Rahman, Mahbubur; Rahman, Mohammed Sayeedur; Sayeedur , Mohammed; Raleting, Thato; Riono, Pandu; Ruswa, Nunurai; Rutebemberwa, Elizeus; Rwabinumi, Mugabe Frank; Senkoro, Mbazi; Sharif, Ahmad Raihan; Sikhondze, Welile; Sismanidis, Charalambos; Sovd, Tugsdelger; Stavia, Turyahabwe; Sultana, Sabera; Suriani, Oster; Thomas, Albertina Martha; Tobing, Kristina; Van der Walt, Martie; Walusimbi, Simon; Zaman, Mohammad Mostafa; Floyd, Katherine; Copas, Andrew; Abubakar, Ibrahim; Rangaka, Molebogeng X.
Tuberculosis (TB) and non-communicable diseases (NCD) share predisposing risk factors. TB-associated NCD might cluster within households affected with TB requiring shared prevention and care strategies. We conducted an individual participant data meta-analysis of national TB prevalence surveys to determine whether NCD cluster in members of households with TB. We identified eligible surveys that reported at least one NCD or NCD risk factor through the archive maintained by the World Health Organization and searching in Medline and Embase from 1 January 2000 to 10 August 2021, which was updated on 23 March 2023. We compared the prevalence of NCD and their risk factors between people who do not have TB living in households with at least one person with TB (members of households with TB), and members of households without TB. We included 16 surveys (n = 740,815) from Asia and Africa. In a multivariable model adjusted for age and gender, the odds of smoking was higher among members of households with TB (adjusted odds ratio (aOR) 1.23; 95% CI: 1.11–1.38), compared with members of households without TB. The analysis did not find a significant difference in the prevalence of alcohol drinking, diabetes, hypertension, or BMI between members of households with and without TB. Studies evaluating household-wide interventions for smoking to reduce its dual impact on TB and NCD may be warranted. Systematically screening for NCD using objective diagnostic methods is needed to understand the actual burden of NCD and inform comprehensive interventions.
Genomic relatedness of colonizing and invasive disease Klebsiella pneumoniae isolates in South African infants
(Nature Research, 2025-03) Olwagen, Courtney P.; Izu, Alane; Khan, Shama; Van der Merwe, Lara; Dean, Nicholas J.; Mabena, Fikile C.; Jones, Stephanie; Kwatra, Gaurav; Andrew, Lubomira; Rajyaguru, Urvi; Donald, Robert G.K.; Simon, Raphael; Said, Mohamed; Nakwa, Firdose L.; Wadula, Jeannette; Strehlau, Renate; Van Niekerk, Anika M.; Naidoo, Niree; Ramsamy, Yogandree; Velaphi, Sithembiso C.; Dangor, Ziyaad; Madhi, Shabir A.
Klebsiella pneumoniae (KPn) colonizes multiple anatomical sites and is a leading cause of invasive disease and death in African children; however, there is no comparative genomic analysis between colonizing and invasive strains. This study investigated the genomic relatedness of KPn colonizing and invasive isolates in South African infants; and evaluated the relative invasiveness of KPn isolates based on sequence types (ST), capsular (KL), and lipopolysaccharide (O) loci by calculating case-carrier ratios (CCRs). There was less genomic diversity amongst invasive (22 ST, 17 K-loci) than colonizing isolates (31 ST, 29 K-loci), with invasive isolates being 8.59-fold and 3.49-fold more likely to harbour genes encoding for multi-drug resistance and yersiniabactin production compared with colonizing isolates. The CCRs for KL102 and O1/O2v2 were > 1, and < 1 for KL8, ST1414, and O1O2v1. Identifying high-risk strains, including KL102 and O1O2v2, that may have a higher potential to cause invasive disease, could enhance risk assessment and management strategies in vulnerable populations.
Post-conflict nutritional status of school-age children in North Wollo zone, Northeast Ethiopia : a multi-center cross-sectional study
(BioMed Central, 2025-08) Dejazmach, Zelalem; Ayal, Birtukan Gizachew; Kassahun, Woldeteklehaymanot; Kumie, Getinet; Kassa, Muluemebet; Yayeh, Berihun Mulu; Ahmed, Seada Seid; Gela, Abebe Worku; Debash, Habtu; Ayalew, Selamawit; Ameshe, Asmamaw; Alamrew, Abebaw; Asfaw, Mulu Shiferaw; Feleke, Sefineh Fenta; Reta, Melese Abate
BACKGROUND : Conflict invariably disrupts food production in affected areas, exacerbates food insecurity, and results in population displacement. In 2021, the invasion of the Amhara region by the Tigrayan armed group led to widespread impoverishment of much of Amhara population. The conflict particularly exacerbated malnutrition rates in the North Wollo Zone. Despite this, studies focusing on undernutrition in conflict-affected areas within the Zone have not yet been documented. Therefore, this study assessed post-conflict nutritional status of school-age children in Northeast Ethiopia. METHODS : Cross-sectional study was conducted from April to May 2022 within the community, involving 584 school-age children. Socio-demographic data was collected through a structured questionnaire, and anthropometric measurements were transformed into indices using the World Health Organization’s Anthro-software. Descriptive and analytical statistical analyses were conducted with a 95% confidence interval. A p-value of less than 0.05 was regarded as statistically significant in the multivariate regression models. RESULTS : Among the 584 participants, 45.7% (95% CI: 42.0–50.0) were found to be stunted, while 33.0% (95% CI: 29.3–37.0) were classified as thin. Stunting was significantly associated with being: age 10–14 years (AOR = 6.16, 95% CI: 3.89–9.78); male (AOR = 1.52, 95% CI: 1.03–2.22); having an employed father (AOR = 3.40, 95% CI: 1.46–7.92); having farmer father (AOR = 4.70, 95% CI: 2.61–8.47). The odds of thinness were significantly higher among children who were male (AOR = 1.93, 95% CI: 1.23–3.03); lived in rural areas (AOR = 2.84, 95% CI: 1.55–5.20); had a mother who was a housewife (AOR = 4.38, 95% CI: 2.09–9.18) or a merchant (AOR = 4.84, 95% CI: 1.72–13.61); had a merchant father (AOR = 14.06, 95% CI: 6.97–28.35) or employed (AOR = 11.41, 95% CI: 4.33–30.07); and lived in a food-insecure household (AOR = 6.17, 95% CI: 3.84–9.90). CONCLUSIONS : Undernutrition is significant public health concern among school-age children in the conflict-affected study area. Stunting and thinness were significantly linked to factors such as the child’s sex, age, parents’ occupational status. These findings underscore the pressing need to implement health and nutrition programs aimed at enhancing the nutritional status of school-age children in the conflict-affected region.
The global prevalence of biofilm-forming Enterococcus faecalis in clinical isolates : a systematic review and meta-analysis
(BioMed Central, 2025-08) Tamrat, Ephrem; Asmare, Zelalem; Geteneh, Alene; Sisay, Assefa; Getachew, Ermias; Kassanew, Brhanu; Dessale, Mesfin; Gashaw, Yalewayker; Jemal, Abdu; Gashaw, Muluken; Bazezew, Alembante; Gedfie, Solomon; Kassahun, Woldeteklehaymanot; Abebe, Wagaw; Dejazmach, Zelalem; Misganaw, Tadesse; Ashagre, Agenagnew; Nigatie, Marye; Damtie, Abebe Adisu; Alemu, Bewuketu Belete; Tefera, Zewdu; Mezgebu, Bahriew; Kumie, Getinet; Kiros, Mulugeta;; Reta, Melese Abate
BACKGROUND : Enterococcus faecalis (E. faecalis) is a major cause of healthcare-associated infections (HAIs). It exhibits a strong biofilm-forming ability, which contributes to treatment resistance and persistence. Despite its clinical relevance, the global prevalence of biofilm-forming E. faecalis remains poorly defined. This study aimed to estimate the pooled prevalence of biofilm-forming E. faecalis in clinical isolates worldwide. METHODS : Following PRISMA 2020 guidelines, we systematically searched PubMed, Scopus, ScienceDirect, Google Scholar, and institutional repositories for studies published between 2015 and 2024. A total of 56 studies involving 3,739 clinical isolates met the inclusion criteria. We used a random-effects model to estimate pooled prevalence and conducted subgroup analyses based on WHO region, continent, publication year, specimen type, and biofilm detection method. Meta-regression and sensitivity analyses assessed heterogeneity and robustness. Publication bias was evaluated using Egger’s test and corrected with trim-and-fill analysis. RESULTS : The global pooled prevalence of biofilm-forming E. faecalis was 68.68% (95% CI: 61.33–76.02%), with significant heterogeneity (I² = 99.30%). By WHO region, prevalence ranged from 57.93% (95% CI: 41.01–71.85%) in South-East Asia to 73.66% (95% CI: 63.40–83.92%) in the Eastern Mediterranean. By continent, South America (all from Brazil) showed the highest prevalence at 89.79% (95% CI: 73.02–106.56%). Studies from 2021 to 2024 reported higher prevalence (76.18%, 95% CI: 66.25–86.11%) than those from 2015 to 2020. Among specimens, urine showed the highest prevalence (80.47%, 95% CI: 61.17–99.77%). Among biofilm-positive isolates, 47.92% (95% CI: 39.34–56.51%) were strong producers. Meta-regression identified WHO region (p = 0.005) and specimen type (p = 0.043) as significant sources of heterogeneity. Egger’s test indicated publication bias (p = 0.0066), but trim-and-fill analysis yielded a consistent adjusted prevalence of 68.08%. CONCLUSION : Biofilm formation is highly prevalent in E. faecalis clinical isolates globally, with substantial regional and specimen-based variation. These findings highlight the urgent need for standardized biofilm detection protocols, improved infection prevention and control, tailored antibiotic stewardship, and the development of anti-biofilm therapies to mitigate biofilm-associated resistance and enhance patient outcomes.
Sputum and tongue swab molecular testing for the in-home diagnosis of tuberculosis in unselected household contacts : a cost and cost-effectiveness analysis
(Oxford University Press, 2025-07) Bezuidenhout, Charl; Long, Lawrence; Nichols, Brooke; Meyer-Rath, Gesine; Fox, Matthew P.; Theron, Grant; Fourie, Bernard P.; Olifant, Sharon; Penn-Nicholson, Adam; Ruhwald, Morten; Medina-Marino, Andrew
BACKGROUND : Delayed and missed diagnoses are a persistent barrier to tuberculosis (TB) control, driven by difficulties collecting sputum and an unmet need for decentralized testing. Household contact investigation with point-of-care (POC) testing of noninvasive specimens may offer a cost-effective solution to strengthen active case finding. METHODS : In-home molecular POC testing was conducted using sputum and tongue specimens collected from household contacts of people with confirmed TB residing in South Africa. A health economic assessment was executed to estimate and compare the cost and cost-effectiveness of different in-home POC testing strategies against centralized sputum testing (standard of care) from a provider's perspective. The primary cost-effectiveness outcome was measured as the incremental cost per additional household contact with TB detected and linked to treatment. Decision analytic modeling was used to estimate and compare incremental cost-effectiveness ratios across strategies. RESULTS : The total implementation cost of delivering the standard of care to 300 households over a 2-year period was $85 188. Strategies that integrated in-home POC testing ranged from $88 672 to $97 271. The cost per test for in-home POC sputum testing was the highest at $20.08. Two strategies, POC sputum testing and POC combined sputum and individual tongue swab testing, were the most cost-effective with incremental cost-effectiveness ratios of $641 and $775, respectively, both below a $2760 willingness-to-pay threshold. CONCLUSIONS : In-home POC molecular TB testing strategies that use combination testing of tongue swabs and sputum specimens can meaningfully improve the number of people tested, diagnosed, and notified during household contact investigation while being cost-effective.
In-home TB testing using geneXpert edge is acceptable, feasible, and improves the proportion of symptomatic household contacts tested for TB : a proof-of-concept study
(Oxford University Press, 2024-06) Medina-Marino, Andrew; Bezuidenhout, Dana; Bezuidenhout, Charl; Facente, Shelley N.; Fourie, Bernard P.; Shin, Sanghyuk S.; Penn-Nicholson, Adam; Theron, Grant
BACKGROUND : Household contact investigations are effective for finding tuberculosis (TB) cases but are hindered by low referral uptake for clinic-based evaluation and testing. We assessed the acceptability and feasibility of in-home testing of household contacts (HHC) using the GeneXpert Edge platform. METHODS : We conducted a 2-arm, randomized study in Eastern Cape, South Africa. HHCs were verbally assessed using the World Health Organization-recommended 4-symptom screen. Households with ≥1 eligible symptomatic contact were randomized. Intervention households received in-home GeneXpert MTB/RIF molecular testing. GeneXpert-positive HHCs were referred for clinic-based treatment. Standard-of-care households were referred for clinic-based sputum collection and testing. We defined acceptability as agreeing to in-home testing and feasibility as generation of valid Xpert MTB/RIF results. The proportion and timeliness of test results received was compared between groups. RESULTS : Eighty-four households were randomized (n = 42 per arm). Of 100 eligible HHCs identified, 98/100 (98%) provided consent. Of 51 HHCs allocated to the intervention arm, all accepted in-home testing; of those, 24/51 (47%) were sputum productive and 23/24 (96%) received their test results. Of 47 HCCs allocated to standard-of-care, 7 (15%) presented for clinic-based TB evaluation, 6/47 (13%) were tested, and 4/6 (67%) returned for their results. The median (interquartile range) number of days from screening to receiving test results was 0 (0) and 16.5 (11-15) in the intervention and standard-of-care arms, respectively. CONCLUSIONS : In-home testing for TB was acceptable, feasible, and increased HHCs with a molecular test result. In-home testing mitigates a major limitation of household contact investigations (dependency on clinic-based referral), revealing new strategies for enhancing early case detection.
A prolonged outbreak of enteric fever associated with illegal miners in the City of Matlosana, South Africa, November 2020–September 2022
(Oxford University Press, 2024-02-28) Sekwadi, Phuti; Smith, Anthony Marius; Maruma, Wellington; Mongologa, Gift; Tsele, Grace; Ngomane, Mimmy; Tau, Nomsa; Williams, Shannon; Disenyeng, Bolele; Sebiloane, Mahlaku; Johnston, Leigh; Erasmus, Linda Kathleen; Thomas, Juno
BACKGROUND : In South Africa, the annual incidence of enteric fever averaged 0.1 per 100 000 persons between 2003 and 2018. During 2021 an increase in the number of enteric fever cases was observed. An outbreak investigation was conducted to determine the magnitude and source of the outbreak. METHODS : We performed a cross-sectional descriptive study. Data were collected through telephonic or face-to-face interviews with cases or proxies via a standardized case investigation form. Whole genome sequencing was performed on all Salmonella Typhi isolates. Drinking water samples were collected, tested, and analyzed. Descriptive analysis was performed with Microsoft Excel. RESULTS : Between January 2020 and September 2022, a cluster of 53 genetically highly related Salmonella Typhi isolates was identified from 5 provinces in South Africa. Isolates associated with the cluster showed ≤5 allelic differences, as determined following core genome multilocus sequence typing analysis. Most cases (60%, 32/53) were in the North West province. Males represented 68% (36/53). Of these, 72% (26/36) were aged 15 to 49 years, with a median age of 31 years. Where occupation was known within this age group, 78% (14/18) were illegal gold miners. Illegal miners reported illness onset while working underground. Five municipal tap water samples were tested and showed no evidence of fecal contamination. CONCLUSIONS : This outbreak predominantly affected illegal gold miners, likely due to the consumption of contaminated groundwater while working in a gold mine shaft. In addition, this investigation highlights the value of whole genome sequencing to detect clusters and support epidemiologic investigation of enteric fever outbreaks.
Business model innovation based on disruptive technologies : a critical success factors categorization
(IADIS, 2024) Edwards, Mikhail David; Smuts, Hanlie
Business model innovation (BMI) holds significant importance in today's digital landscape, empowering enterprises to leverage disruptive technology for value creation and competitive advantage. However, the rapid evolution of these technologies presents various challenges, including uncertain market conditions, potential financial risks during the initial phases, employee resistance, and the risk of distraction from core responsibilities. This research aimed to identify the characteristics essential for the successful implementation of BMI through effective utilization of disruptive technologies. This was accomplished through a thorough review of existing literature, organizing critical success factors into the business model canvas framework, and applying a framework for identifying and classifying digital technologies based on demand. The findings underscored the importance of trust, efficiency, and adaptability across various BMI components. Technologies like Artificial Intelligence enhance objective alignment and personalized client experiences, while blockchain technology fosters trust and transparency. Cloud computing, on the other hand, enhances resource accessibility and flexibility. To achieve optimal BMI in today's digital landscape, it is important for organisations to proactively integrate these technologies into their operations, while fostering adaptability and engaging stakeholders.
Immunogenicity and safety following a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine with Matrix-MTM adjuvant (NVX-CoV2373) versus a primary series in people living with and without HIV-1 infection in South Africa : a randomized crossover phase 2a/2b trial
(Taylor and Francis, 2024-12) Shinde, Vivek; Koen, Anthonet Lombard; Hoosain, Zaheer; Archary, Moherndran; Bhorat, Qasim; Fairlie, Lee; Lalloo, Umesh; Masilela, Mduduzi S.L.; Moodley, Dhayendre; Hanley, Sherika; Fouche, Leon Frederik; Louw, Cheryl; Tameris, Michele; Singh, Nishanta; Goga, Ameena Ebrahim; Dheda, Keertan; Grobbelaar, Coert; Joseph, Natasha; Lombaard , Johan J.; Mngqibisa, Rosie; Bhorat, As’ad Ebrahim; Benade, Gabriella; Lalloo, Natasha; Pitsi, Anna; Vollgraaff, Pieter-Louis; Luabeya, Angelique; Esmail, Aliasgar; Petrick, Friedrich G.; Jose, Aylin Oommen; Foulkes, Sharne; Ahmed, Khatija; Thombrayil, Asha; Kalonji, Dishiki; Cloney-Clark, Shane; Zhu, Mingzhu; Bennett, Chijioke; Albert, Gary; Marcheschi, Alex; Plested, Joyce S.; Neal, Susan; Chau, Gordon; Cho, Iksung; Fries, Louis; Glenna, Greg M.; Madhi, Shabir A.
COVID-19 remains a global public health issue and an improved understanding of vaccine performance in immunocompromised individuals, including people living with HIV (PLWH), is needed. Initial data from the present study's pre-crossover/booster phase were previously reported. This phase 2a/b clinical trial in South Africa (2019nCoV-501/NCT04533399) revisits 1:1 randomly assigned HIV-negative adults (18-84 years) and medically stable PLWH (18-64 years) who previously received two NVX-CoV2373 doses (5 μg recombinant Spike protein with 50 μg Matrix-M™ adjuvant) or placebo. During the 6-month blinded crossover/booster phase, NVX-CoV2373 recipients could receive a single NVX-CoV2373 booster dose and placebo recipients a 2-dose NVX-CoV2373 primary series. NVX-CoV2373 safety and immunogenicity were assessed according to prior SARS-CoV-2 infection and HIV status. Post-crossover, 1900/3793 NVX-CoV2373 recipients were assigned another dose, and 1893/3793 placebo recipients were assigned NVX-CoV2373 primary series. Approximately 56% of the participants were SARS-CoV-2-seropositive ("seropositive") at crossover (6% PLWH). In seropositive participants (HIV-negative and PLWH), booster-dose anti-spike IgG, MN50 and hACE2 inhibition responses increased to similar levels, exceeding those in seronegative participants. In primary-series and booster cohorts, seronegative PLWH showed higher neutralizing responses (4.9- to 5.5-fold, respectively) versus peak pre-crossover primary-series responses. The safety profile was similar among the pre-crossover/booster phase groups; solicited and unsolicited adverse events were infrequent in all groups. A single NVX-CoV2373 booster dose substantially increased antibodies. All baseline seropositive participants showed higher immune responses than seronegative participants. These findings support use of NVX-CoV2373, including in immunocompromised individuals.
Molecular epidemiology of carbapenemase‑producing Klebsiella pneumoniae in Gauteng South Africa
(Nature Research, 2024-11-09) Salvador-Oke, Kafilat Taiwo; Pitout, Johann D.D.; Peirano, Gisele; Strydom, Kathy‑Anne; Kingsburgh, Chanel; Ehlers, Marthie Magdaleen; Ismail, Arshad; Takawira, Faustinos T.; Kock, Marleen M.; marleen.kock@up.ac.za
Klebsiella pneumoniae multidrug-resistant (MDR) high-risk clones drive the spread of antimicrobial resistance (AMR) associated infections, resulting in limited therapeutic options. This study described the genomic characteristics of K. pneumoniae MDR high-risk clones in Gauteng, South Africa. Representative carbapenem-resistant [K. pneumoniae carbapenemase (KPC)-2, New-Delhi metallo-beta (β)-lactamase (NDM)-1, oxacillinase (OXA)-181, OXA-232, OXA-48, Verona integron-encoded metallo-β-lactamase (VIM)-1] K. pneumoniae isolates (n = 22) obtained from inpatient and outpatient’s urine (n = 9) and inpatients rectal carriage (n = 13) were selected for short-read whole genome sequencing. Klebsiella pneumoniae population include sequence type (ST)-307 (n = 3), ST2497 (n = 5) and ST17 (n = 4). The ST17 strains were exclusively obtained from rectal screening. Ten isolates co-harboured carbapenemase genes including β-lactamase gene encoding KPC-2 + OXA-181, NDM-1 + OXA-48 and NDM-1 + OXA-181. One ST307 isolate (UP-KT-73CKP) co-harboured three carbapenemase genes (blaNDM-1 + blaOXA-48 + blaOXA-181), while all the ST2497 strains co-harboured (blaNDM-1 + blaOXA-232). Phenotypically, hypermucoviscosity was observed in a single ST307 isolate. The ST307 isolate UP-KT-151UKP harboured colibactin genotoxins. The following mobile genetic elements were detected: plasmids [incompatibility group (Inc)-FIB(K), IncX3], and bacteriophages [e.g. Klebsi_ST16_OXA48phi5.4_NC_049450, Klebsi_3LV2017_NC_047817(36)]. The study highlights the importance of local genomic surveillance systems to characterise K. pneumoniae MDR high-risk clones. This data will aid in designing infection and prevention measures for limiting the spread of carbapenemase-producing K. pneumoniae in Gauteng, South Africa.
Missed rifampicin and isoniazid resistance by commercial molecular assays
(South African Medical Association, 2024-07) Richards, L.; Ismail, Farzana; Nel, J.; Omar, Shaheed Vally
Drug-resistant tuberculosis (TB) has poor outcomes unless resistance is detected early, ideally by commercially available molecular tests. We present a case of occult multidrug-resistant TB where both rifampicin and isoniazid resistance were missed by molecular testing and were only identified by phenotypic testing.
Innovative timing strategies for tuberculosis household contact investigation : cost-effectiveness analysis from a randomized trial in rural and urban South Africa (Kharituwe Study)
(Elsevier, 2025-06) Young, Neenah; Biché, Patrick; Mohlamonyane, Mbali; Morolo, Matshidiso; Maholwana, Babalwa; Ahmed, Khatija; Martinson, Neil; Hanrahan, Colleen F.; Dowdy, David W.
BACKGROUND : Household contact investigation (HCI) for tuberculosis (TB) is recommended but often limited by resource constraints, particularly for individuals unavailable during business hours. METHODS : We conducted an economic evaluation from January 1, 2022, through December 31, 2022, nested within a randomized trial in South Africa (“Kharituwe”) comparing standard HCI for TB and two novel strategies: HCI during holiday periods in a rural setting and off-peak HCI during weekends and evenings in an urban setting. Costs were derived from 2022 expenditures, and secondary TB cases were defined by positive sputum cultures. As a secondary outcome of the Kharituwe Study, we assessed the incremental cost-effectiveness ratio (ICER) of each strategy against a hypothetical no-HCI scenario from the health system perspective in 2022 US dollars. Cost-effectiveness was assessed using a country-specific willingness-to-pay threshold of US$3015 per disability-adjusted life year (DALY) averted. The trial is registered with clincaltrials.gov (NCT04520113). FINDINGS : Relative to a hypothetical no-HCI approach, standard HCI was estimated to cost US$1400 [95% uncertainty interval (UI): $1000–$2100] per DALY averted in the urban setting and US$3600 [95% UI: $2500–$5400] in the rural setting. Corresponding cost-effectiveness ratios were US$1900 [95% UI: $1300–$2800] for off-peak (urban) and US$6400 [$3900–$10,000] for holiday-based (rural) HCI. Personnel costs, travel costs (in the rural setting), and TB prevalence among contact persons were primary drivers of cost-effectiveness. INTERPRETATION : HCI for TB is likely cost-effective in urban South Africa and may be cost-effective in rural settings, which face barriers including long travel times and lower TB prevalence. Holiday-based HCI was not found to be cost-effective. Integrating HCI for TB into broader home-based interventions may improve cost-effectiveness.
Expediting pathogen genomics adoption for enhanced foodborne disease surveillance in Africa
(Elsevier, 2025-01) Kanzi, Aquillah M.; Smith, Stella I.; Msefula, Chisomo; Mwaba, John; Ajayi, Abraham; Kwenda, Geoffrey; Tanui, Collins K.; Smith, Anthony Marius; Bester, Linda A.; Derra, Firehiwot A.; Yamba, Kaunda; Banda, Daniel L.; Kalule, John B.; Kumburu, Happiness H.; Fakim, Yasmina J.; Sithole, Nyasha; Njage, Patrick M.K.; Chikuse, Francis F.; Ondoa, Pascale; Tessema, Sofonias K.; Foster-Nyarko, Ebenezer
The role of genomics in public health surveillance has been accentuated by its crucial contributions during the COVID-19 pandemic, demonstrating its potential in addressing global disease outbreaks. While Africa has made strides in expanding multi-pathogen genomic surveillance, the integration into foodborne disease (FBD) surveillance remains nascent. Here we highlight the critical components to strengthen and scale-up the integration of whole genome sequencing (WGS) in foodborne disease surveillance across the continent. We discuss priority use-cases for FBD, and strategies for the implementation. We also highlight the major challenges such as data management, policy and regulatory frameworks, stakeholder engagement, the need for multidisciplinary collaborations and the importance of robust monitoring and evaluation, aiming to bolster Africa's preparedness and response to future health threats.
Prevalence of genes encoding carbapenem-resistance in Klebsiella pneumoniae recovered from clinical samples in Africa : systematic review and meta-analysis
(BioMed Central, 2025-04) Sisay, Assefa; Kumie, Getinet; Gashaw, Yalewayker; Nigatie, Marye; Gebray, Habtamu Mesele; Reta, Melese Abate
Please read abstract in the article.
Prevalence of colistin-resistant Enterobacteriaceae isolated from clinical samples in Africa: a systematic review and meta-analysis
(BioMed Central, 2025-03) Gashaw, Yalewayker; Asmare, Zelalem; Tigabie, Mitkie; Sisay, Asefa; Getatachew, Ermias; Tadesse, Selamyhun; Bitew, Getachew; Ashagre, Agenagnew; Misganaw, Tadesse; Gashaw, Muluken; Kassahun, Woldeteklehaymanot; Dejazimach, Zelalem; Jemal, Abdu; Gedfie, Solomon; Kumie, Getinet; Nigatie, Marye; Gelaw, Baye; Abebe, Wagaw; Kidie,Atitegeb Abera; Abate, Biruk Beletew; Reta, Melese Abate; Gelaw, Baye
BACKGROUND : Antimicrobial resistance among Enterobacteriaceae poses a significant global threat, particularly in developing countries. Colistin, a critical last-resort treatment for infections caused by carbapenem-resistant and multidrug-resistant strains, is increasingly facing resistance due to inappropriate use of colistin and the spread of plasmid-mediated resistance genes. Despite the significance of this issue, comprehensive and updated data on colistin resistance in Africa is lacking. Thus, the current study was aimed to determine the pooled prevalence of colistin-resistant Enterobacteriaceae in Africa. METHODS : A systematic search was conducted across PubMed, Scopus, ScienceDirect, and Google Scholar to identify relevant studies. Forty-one studies reporting on the prevalence of colistin resistance in Enterobacteriaceae isolates from clinical specimens in Africa were included in the analysis. Stata 17 software was used to calculate the pooled prevalence of colistin resistance, employing a random-effects model to determine the event rate of resistance. Heterogeneity across studies was assessed using the I2 statistic, and publication bias was evaluated using Egger’s test. Subgroup analyses were performed to address any identified heterogeneity. RESULTS : This systematic review analyzed the colistin resistance profile of 9,636 Enterobacteriaceae isolates. The overall pooled prevalence of colistin resistance was 26.74% (95% CI: 16.68–36.80). Subgroup analysis by country revealed significant variability in resistance rates, ranging from 0.5% in Djibouti to 50.95% in South Africa. Species-specific prevalence of colistin resistance was as follows: K. pneumoniae 28.8% (95% CI: 16.64%-41.05%), E. coli 24.5% (95% CI: 11.68%-37.3%), Proteus spp. 50.0% (95% CI: 6.0%-106.03%), and Enterobacter spp. 1.22% (95% CI: -0.5%-3.03%). Analysis based on AST methods revealed significant differences in colistin resistance rates (p = 0.001). The resistance rates varied between 12.60% for the disk diffusion method and 28.0% for the broth microdilution method. Additionally, a subgroup analysis of clinical specimens showed significant variation (p < 0.001) in colistin resistance. Stool specimen isolates had the highest resistance rate at 42.0%, while blood specimen isolates had a much lower resistance rate of 3.58%. CONCLUSIONS : Colistin resistance in Enterobacteriaceae is notably high in Africa, with significant variation across countries. This underscores the urgent need for effective antimicrobial stewardship, improved surveillance, and the development of new antibiotics.

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