Research Articles (Medical Microbiology)

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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; 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
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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.
Antimicrobial resistance pattern of Acinetobacter baumannii clinical isolate in Ethiopia. A systematic review and meta-analysis
(BioMed Central, 2025-04) Asmare, Zelalem; Tamrat, Ephrem; Erkihun, Mulat; Endalamaw, Kirubel; Alelign, Dagninet; Getie, Molla; Sisay, Assefa; Gashaw, Yalewayker; Reta, Melese Abate
BACKGROUND : Antimicrobial resistance (AMR) is a growing global health threat. Acinetobacter baumannii (A. baumannii) emerged as one of the most concerning critical priority pathogens due to its ability to develop resistance to multiple antimicrobial agents. In Ethiopia, the public health impact of AMR is increasingly significant, with A. baumannii responsible for a variety of infections. Although A. baumannii causes a range of infections in Ethiopian patients, the drug resistance status of the clinical isolates has not been thoroughly assessed. Therefore, this systematic review and meta-analysis aimed to determine the country-wide AMR of A. baumannii. METHODS : This systematic review and meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We conducted a search of articles on PubMed, Web of Science, Science Direct, Scopes electronic databases, Google Scholar search engine, and institutional repositories/libraries for studies published between 2015 and 2024. Eligible studies on A. baumannii-related infections and AMR in Ethiopia were assessed for quality using the Joanna Briggs Institute (JBI) criteria. Data on study characteristics were extracted, and statistical analyses, including heterogeneity (Invers of variance), publication bias (Eggers test), and subgroup analyses, were performed using STATA 17.0. A random effect model was used to compute the pooled prevalence of AMR. RESULTS : This systematic review and meta-analysis of 26 Ethiopian studies (26,539 participants) found an A. baumannii prevalence of 3.99% (95% CI: 3.01–4.98%) and 9.13% of all bacterial infections (95% CI: 6.73–11.54%). The most common infections were surgical site infections, urinary tract infections, pneumonia, and sepsis. Pooled resistance to antibiotics varied, with amikacin showing the lowest resistance (20.27%) (95% CI: 11.51–29.03) and cefotaxime the highest (83.18) (95% CI: 71.87–94.48). A pooled multi-drug resistant (MDR) A. baumannii was found in 88.22% (95% CI: 82.28–94.15) of isolates, with regional and infection-type variations, particularly in higher prevalence in Oromia and Amhara regions and sepsis cases. CONCLUSION : This systematic review underscores the alarming rise of antimicrobial resistance in A. baumannii, particularly against carbapenems. The findings highlight a high prevalence of MDR A. baumannii and widespread extended-spectrum beta-lactamase production, with notable regional variations in resistance patterns. These high resistance rates reinforce A. baumannii as a critical global health threat, necessitating urgent interventions such as enhanced antimicrobial stewardship programs, improved infection control measures, and the development of alternative treatment strategies. Healthcare professionals, policymakers, and researchers must collaborate to mitigate the clinical and public health impact of this pathogen. PROTOCOL REGISTRATION : This systematic review and meta-analysis was registered on PROSPERO (Registration ID: CRD42024623927).
Does a waiting room increase same-day treatment for sexually transmitted infections among pregnant women? A quality improvement study at South African primary healthcare facilities
(BioMed Central, 2025-04) Gigi, Ranjana M.S.; Mdingi, Mandisa M.; Butikofer, Lukas; Babalola, Chibuzor M.; Klausner, Jeffrey D.; Medina-Marino, Andrew; Muzny, Christina A.; Taylor, Christopher M.; Van de Wijgert, Janneke H.H.M.; Peters, Remco P.H.; Low, Nicola
BACKGROUND : Same-day testing and treatment of curable sexually transmitted infections (STI) is a strategy to reduce infection duration and onward transmission. South African primary healthcare facilities often lack sufficient waiting spaces. This study aimed to assess the proportion of, and factors influencing, pregnant women waiting for on-site STI test results before and after the installation of clinic-based waiting rooms. METHODS : We conducted an observational quality improvement study at 5 public primary healthcare facilities in South Africa from March 2021 to May 2023. The intervention was the installation of a waiting room in two clinics. Three clinics were used as comparators: two already had a waiting room in an existing building and one had access to a shared waiting area. The outcome was the percentage of women who waited for their STI test results. We conducted univariable and multivariable analyses and report marginal risk differences (with 95% confidence intervals, CI) of the proportions of women who waited for results. A subset of women answered structured questions about factors influencing their decision to wait for results. RESULTS : We analysed data from 624 women across the 5 facilities. Overall, 36% (95% CI 31 to 40) waited for their test results (range 7 to 89%). In the two intervention clinics, 17% (95% CI 11 to 24) waited for results before the introduction of a waiting room and 10% (95% CI 5 to 18) after (crude absolute difference − 7% (95% CI -16 to + 3), adjusted difference, -6% (95% CI -17 to + 5)). The percentages of pregnant women waiting for STI test results were higher throughout the study period in 2 clinics which always had a dedicated waiting room than in 2 clinics where a waiting room was installed, or in 1 clinic, which only had access to a shared waiting area. Most women reported before testing that they did not intend to wait and none of the suggested factors would change their decision. CONCLUSIONS : Introduction of a waiting room did not increase the proportion of women who waited for their results in this observational study. Future studies should investigate infrastructure, individual and test-based factors that affect same-day STI testing and treatment.
Twice-yearly Lenacapavir or daily F/TAF for HIV prevention in cisgender women
(Massachusetts Medical Society, 2024-10) Bekker, Linda-Gail; Das, Moupali; Karim, Quarraisha Abdool; Ahmed, Khatija; Batting, Joanne; Brumskine, William; Gill, Katherine; Harkoo, Ishana; Jaggernath, Manjeetha; Kigozi, Godfrey; Kiwanuka, Noah; Kotze, Philip; Lebina, Limakatso; Louw, Cheryl; Malahleha, Moelo; Manentsa, Mmatsie; Mansoor, Leila E.; Moodley, Dhayendre; Naicker, Vimla; Naidoo, Logashvari; Naidoo, Megeshinee; Nair, Gonasagrie; Ndlovu, Nkosiphile; Palanee-Phillips, Thesla; Panchia, Ravindre; Pillay, Saresha; Potloane, Disebo; Selepe, Pearl; Singh, Nishanta; Singh, Yashna; Spooner, Elizabeth; Ward, Amy M.; Zwane, Zwelethu; Ebrahimi, Ramin; Zhao, Yang; Kintu, Alexander; Deaton, Chris; Carter, Christoph C.; Baeten, Jared M.; Kiweewa, Flavia Matovu
BACKGROUND : There are gaps in uptake of, adherence to, and persistence in the use of preexposure prophylaxis for human immunodeficiency virus (HIV) prevention among cisgender women. METHODS : We conducted a phase 3, double-blind, randomized, controlled trial involving adolescent girls and young women in South Africa and Uganda. Participants were assigned in a 2:2:1 ratio to receive subcutaneous lenacapavir every 26 weeks, daily oral emtricitabine–tenofovir alafenamide (F/TAF), or daily oral emtricitabine–tenofovir disoproxil fumarate (F/TDF; active control); all participants also received the alternate subcutaneous or oral placebo. We assessed the efficacy of lenacapavir and F/TAF by comparing the incidence of HIV infection with the estimated background incidence in the screened population and evaluated relative efficacy as compared with F/TDF. RESULTS : Among 5338 participants who were initially HIV-negative, 55 incident HIV infections were observed: 0 infections among 2134 participants in the lenacapavir group (0 per 100 person-years; 95% confidence interval [CI], 0.00 to 0.19), 39 infections among 2136 participants in the F/TAF group (2.02 per 100 person-years; 95% CI, 1.44 to 2.76), and 16 infections among 1068 participants in the F/TDF group (1.69 per 100 person-years; 95% CI, 0.96 to 2.74). Background HIV incidence in the screened population (8094 participants) was 2.41 per 100 person-years (95% CI, 1.82 to 3.19). HIV incidence with lenacapavir was significantly lower than background HIV incidence (incidence rate ratio, 0.00; 95% CI, 0.00 to 0.04; P<0.001) and than HIV incidence with F/TDF (incidence rate ratio, 0.00; 95% CI, 0.00 to 0.10; P<0.001). HIV incidence with F/TAF did not differ significantly from background HIV incidence (incidence rate ratio, 0.84; 95% CI, 0.55 to 1.28; P=0.21), and no evidence of a meaningful difference in HIV incidence was observed between F/TAF and F/TDF (incidence rate ratio, 1.20; 95% CI, 0.67 to 2.14). Adherence to F/TAF and F/TDF was low. No safety concerns were found. Injection-site reactions were more common in the lenacapavir group (68.8%) than in the placebo injection group (F/TAF and F/TDF combined) (34.9%); 4 participants in the lenacapavir group (0.2%) discontinued the trial regimen owing to injection-site reactions. CONCLUSIONS : No participants receiving twice-yearly lenacapavir acquired HIV infection. HIV incidence with lenacapavir was significantly lower than background HIV incidence and HIV incidence with F/TDF.

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