333 research outputs found
Correction: Overcoming barriers to NHS adoption of innovative IPC products: A qualitative study of SMEs in the Liverpool city region (PLoS One (2025) 20:9 (e0331688) DOI: 10.1371/journal.pone.0331688)
No full textThere are errors in the Author Contributions. The correct contributions are: Conceptualization: Rocío Villacorta Linaza, Janet Hemingway, Adam P. Roberts, Nicholas Feasey. Data curation: Rocío Villacorta Linaza. Formal analysis: Rocío Villacorta Linaza, Adam P. Roberts. Investigation: Rocío Villacorta Linaza, Daire Cantillon. Methodology: Rocío Villacorta Linaza, Daire Cantillon. Project administration: Rocío Villacorta Linaza, Daire Cantillon Writing – original draft: Rocío Villacorta Linaza. Writing – review & editing: Janet Hemingway, Adam P. Roberts, Becky Jones-Philips, Miriam Taegtmeyer, Richard L. Wright, Daire Cantillon, Maria Moore, Russell Dacombe, Ezekiel Boro, Aaron Argomandkhah, Carolina Velasco, Nicholas Feasey.</p
Evaluation of Xpert MTB/RIF for detection of tuberculosis from blood samples of HIV-infected adults confirms Mycobacterium tuberculosis bacteremia as an indicator of poor prognosis.
No full textTuberculosis (TB) remains a leading cause of death among HIV-infected adults, in part because of delayed diagnosis and therefore delayed initiation of treatment. Recently, the Gene-Xpert platform, a rapid, PCR-based diagnostic platform, has been validated for the diagnosis of TB with sputum. We have evaluated the Xpert MTB/RIF assay for the diagnosis of Mycobacterium tuberculosis bacteremia and investigated its impact on clinical outcomes. Consecutive HIV-infected adults with fever and cough presenting to Queen Elizabeth Central Hospital, Blantyre, Malawi, were recruited and followed up for 2 months. At presentation, three sputum samples were examined by smear, culture, and Xpert MTB/RIF assay for the presence of M. tuberculosis and blood was drawn for PCR with Xpert, for mycobacterial culture (Myco/F Lytic), and for aerobic culture. One hundred four patients were recruited, and 44 (43%) were sputum culture positive for M. tuberculosis. Ten were Xpert blood positive, for a sensitivity of 21% and a specificity of 100%. The 2-week mortality rate was significantly higher among patients who were Xpert blood positive than among those who were negative (40% versus 3%; multivariate odds ratio [OR] for death if positive, 44; 95% confidence interval [CI], 3 to 662). This effect persisted on assessment of the mortality rate at 2 months (40% versus 11%; OR, 5.6; 95% CI, 1.3 to 24.6). When screening uncomplicated patients presenting with a productive cough for pulmonary TB, Xpert blood offers no diagnostic advantage over sputum testing. Despite this, Xpert blood positivity is highly predictive of early death and this test rapidly identifies a group of patients in urgent need of initiation of treatment
An assessment of infection prevention and control implementation in Malawian hospitals using the WHO Infection Prevention and Control Assessment Framework (IPCAF) tool
No full textFunding: Dorica Ng'ambi, Thomasena O'Byrne, and Nicholas Feasey were supported by NIHR Global Professorship (NIHR301627).Background: Infection prevention and control (IPC) is important for the reduction of healthcare-associated infections (HAI). The World Health Organization (WHO) developed the IPC Assessment Framework (IPCAF) tool to assess the level of IPC implementation and to identify areas for improvement in healthcare facilities. Methods: A cross -sectional survey was conducted using the WHO IPCAF tool from May to June 2023. The aim was to provide a baseline assessment of the IPC programme and activities within health care facilities in Malawi. Forty healthcare facilities were invited to participate. IPC teams were requested to complete the IPCAF and return the scores. The IPCAF tool scores were assessed as recommended in the WHO IPCAF tool. Results: The response rate was 82.5%. The median IPCAF score was 445 out of 800 corresponding to an intermediate IPC implementation level. The results revealed that 66.7% facilities were at intermediate level, 26.4% at basic level, and 6.9% at advanced level. Most facilities (76%) had an IPC program in place with clear objectives and an IPC focal person. Few had a dedicated budget for IPC. The IPCAF domain “monitoring/audit of IPC practices and feedback” had the lowest median score of 15/100, and in 90% of facilities, no monitoring, audit, and feedback was done. HAI surveillance median score was 40/100, workload, staffing and bed occupancy median score was 45/100. Conclusions: Whilst there has been some degree of implementation of WHO IPC guidelines in Malawi's healthcare system, there is significant room for improvement. The IPCAF tool revealed that monitoring/audit and feedback, HAI surveillance and workload, staffing and bed occupancy need to be strengthened. The IPCAF scoring system may need reconsidering given the centrality of these domains to IPC.Peer reviewe
An investigation into clinical, epidemiological and genomic changes in epidemic Salmonella blood stream infection in Malawi
No full textBloodstream infection (BSI) caused by nontyphoidal serotypes of Salmonella is one of the most important causes of morbidity and mortality in sub-Saharan Africa (SSA). Invasive nontyphoidal Salmonella disease (iNTS) is especially associated with HIV in adults and HIV, malaria and malnutrition in children in this setting. HIV-infected subjects are at particular risk of recurrent disease, both from recrudescence from a sanctuary site and re-infection. Whole- genome sequencing has revealed a novel sequence type (ST) of S. Typhimurium, ST313, is particularly associated with iNTS in SSA and that ST313 display the genomic signature of differential host adaptation. Little is known about African strains of S. Enteritidis.
The Malawi Liverpool Wellcome Trust Clinical Research Programme (MLW) has conducted BSI surveillance in adult and paediatric medical patients in Blantyre, Malawi since 1998, enabling long term trends in iNTS to be described. Paediatric iNTS disease has been placed in the context of malaria, malnutrition and seasonality using structural equation modelling. An observational cohort was recruited to describe changes in adult BSI cases following the roll-out of ART in Blantyre. A longitudinal cohort study with enhanced microbiological surveillance was undertaken to investigate the site of persistence of NTS in HIV infected adults and the effect of recurrence upon the emergence of antimicrobial resistance. Lastly whole-genome sequencing was undertaken to compare invasive, African strains of S. Enteritidis with a reference isolate and to construct a global phylogeny of this serotype.
There have been three epidemics of invasive Salmonella disease in Blantyre, all of which were preceded by the emergence of a multidrug resistant (MDR) strain. These were caused initially by S. Enteritidis which was then followed by S. Typhimurium, but most recently an epidemic of MDR S. Typhi has started. NTS has declined from epidemic levels, but remains an important cause of BSI in Blantyre and has been demonstrated to acquire cephalosporin
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and fluoroquinolone resistance just once through an IncHI2 plasmid. The decline in paediatric malaria is complex and multi-factorial. It cannot be attributed solely to malaria control interventions as has been the case in other settings. All causes of BSI are falling in adults and this is likely to be attributable in part to the hugely successful HIV treatment programme in Blantyre. The rapid initiation of ART appears to rapidly confer protection against recurrence of iNTS and even though more adult patients are surviving into convalescence, in this cohort, no further emergence of extended resistance was seen. Just as there is a distinct African clade of S. Typhimurium, a distinct clade of S. Enteritidis has emerged in SSA, which also possess the genomic signature of differential host adaptation, a novel prophage repertoire and a novel, MDR plasmid.
In Blantyre, iNTS disease has declined from its epidemic peaks, but remains an important cause of BSI. The epidemiology of iNTS is more complex in Blantyre than other settings, but it seems likely that improved in-patient care and measures to control the HIV-pandemic impact on survival and recurrence. Two clades of NTS have emerged from host promiscuous serotypes, both of which have genomic degradation in genes governing potential host range and there is a critical need to understand the environmental niches and transmission pathways of these differentially adapted, invasive clades
Statistical and machine learning methods to estimate the impact of antimicrobial resistance on patient outcomes
No full textAntimicrobial resistance (AMR) presents a complex, universal threat to healthcare whose estimated impact varies widely by population, microbiology, and analytical methodology. Beset by both inter-study heterogeneity and inconsistent availability of relevant evidence, it is challenging for policy-makers and clinicians to make concerted decisions that balance regional, national and international interests. Accordingly, the World Health Organization’s and the UK’s AMR action plans prioritise the use of electronic health record (EHR) data to measure treatment efficacy in light of local patterns of pathogens and AMR. Whilst EHR data are becoming increasingly available, only a few studies have leveraged them to explore clinical and policy-related repercussions of current definitions of AMR for specific pathogens, and of dysregulated systemic infections like sepsis.
In this thesis, I first analysed patient-level clinical, antibiotic and outcome data to investigate the impact of shifting in-vitro definitions of AMR, focusing on bloodstream infections caused by the most implicated pathogens in high-income countries, Escherichia coli (E. coli) and Enterobacterales. I then examined how unsupervised machine learning approaches for clustering can identify phenotypes of these patients with distinct responses to infection and treatment. Broadening the patient population to those with sepsis, I assessed the validity of phenotypes discovered with different variables in dissimilar healthcare ecosystems. In these analyses, a recurring theme was that whilst studies of the baseline condition and treatment of patients can provide useful insights, they do not account for changes in treatment after baseline. However, naïvely estimating the impact of post-baseline changes to treatment is often done, assuming the absence of time-dependent confounding, including the influence of past treatment history and time-varying covariates on subsequent treatment decisions, and ultimately on the outcome of interest. To address this, I employed marginal structural models to study the impact of differential delays to active antibiotic treatment in E. coli and Enterobacterales bloodstream infections.
Overall, the thesis highlights the challenges of estimating the impact of AMR using routinely-collected EHR data. Further work through inter-institutional and international collaboration will accelerate our ability to study, validate, and sensibly act upon AMR in the coordinated, empirically-justified manner that it demands
Conservation of <i>csgD</i> promoter and <i>bcsG</i> single nucleotide polymorphisms in invasive <i>S</i>. Enteritidis and <i>S</i>. Typhimurium lineages.
No full textMaximum likelihood phylogenic trees were constructed from bacterial genome sequences: (A) S. Enteritidis isolates from Feasey et al. [10], and (B) S. Typhimurium isolates from Okoro et al [48], keeping the same general tree shape for comparison purposes. (A) S. Enteritidis isolates were divided into the Central/East African clade (167 isolates) and global epidemic clade (250 isolates), with the distinct region of isolation shown along with presence or absence of the ‘T’ SNP. (B) S. Typhimurium isolates were divided into gastroenteritis-associated and invasive lineages (I and II), with the presence or absence of csgD promoter and bcsG polymorphisms shown.</p
Emerg Infect Dis
No full textNontyphoidal Salmonella is a major cause of bloodstream infections worldwide, and HIV-infected persons and malaria-infected children are at increased risk for the disease. We conducted a systematic literature review to obtain age group-specific, population-based invasive nontyphoidal Salmonella (iNTS) incidence data. Data were categorized by HIV and malaria prevalence and then extrapolated by using 2010 population data. The case-fatality ratio (CFR) was determined by expert opinion consensus. We estimated that 3.4 (range 2.1-6.5) million cases of iNTS disease occur annually (overall incidence 49 cases [range 30-94] per 100,000 population). Africa, where infants, young children, and young adults are most affected, has the highest incidence (227 cases [range 152-341] per 100,000 population) and number of cases (1.9 [range 1.3-2.9] million cases). An iNTS CFR of 20% yielded 681,316 (range 415,164-1,301,520) deaths annually. iNTS disease is a major cause of illness and death globally, particularly in Africa. Improved understanding of the epidemiology of iNTS is needed.BB/J010367/1/Biotechnology and Biological Sciences Research Council/United KingdomBB/L017679/Biotechnology and Biological Sciences Research Council/United KingdomBB/L018845/Biotechnology and Biological Sciences Research Council/United KingdomBB/L018926/Biotechnology and Biological Sciences Research Council/United KingdomR01TW009237/TW/FIC NIH HHS/United State
A prospective study of mortality from cryptococcal meningitis following treatment induction with 1200 mg oral fluconazole in Blantyre, Malawi.
No full textOBJECTIVE: We have previously reported high ten-week mortality from cryptococcal meningitis in Malawian adults following treatment-induction with 800 mg oral fluconazole (57% [33/58]). National guidelines in Malawi and other African countries now advocate an increased induction dose of 1200 mg. We assessed whether this has improved outcomes.
DESIGN: This was a prospective observational study of HIV-infected adults with cryptococcal meningitis confirmed by diagnostic lumbar puncture. Treatment was with fluconazole 1200 mg/day for two weeks then 400mg/day for 8 weeks. Mortality within the first 10 weeks was the study end-point, and current results were compared with data from our prior patient cohort who started on fluconazole 800 mg/day.
RESULTS: 47 participants received fluconazole monotherapy. Despite a treatment-induction dose of 1200 mg, ten-week mortality remained 55% (26/47). This was no better than our previous study (Hazard Ratio [HR] of death on 1200 mg vs. 800 mg fluconazole: 1.29 (95% CI: 0.77-2.16, p = 0.332)). There was some evidence for improved survival in patients who had repeat lumbar punctures during early therapy to lower intracranial pressure (HR: 0.27 [95% CI: 0.07-1.03, p = 0.055]).
CONCLUSION: There remains an urgent need to identify more effective, affordable and deliverable regimens for cryptococcal meningitis
rPinecone: Define sub-lineages of a clonal expansion via a phylogenetic tree.
No full textThe ability to distinguish different circulating pathogen clones from each other is a fundamental requirement to understand the epidemiology of infectious diseases. Phylogenetic analysis of genomic data can provide a powerful platform to identify lineages within bacterial populations, and thus inform outbreak investigation and transmission dynamics. However, resolving differences between pathogens associated with low-variant (LV) populations carrying low median pairwise single nucleotide variant (SNV) distances remains a major challenge. Here we present rPinecone, an R package designed to define sub-lineages within closely related LV populations. rPinecone uses a root-to-tip directional approach to define sub-lineages within a phylogenetic tree according to SNV distance from the ancestral node. The utility of this software was demonstrated using both simulated outbreaks and real genomic data of two LV populations: a hospital outbreak of methicillin-resistant Staphylococcus aureus and endemic Salmonella Typhi from rural Cambodia. rPinecone identified the transmission branches of the hospital outbreak and geographically confined lineages in Cambodia. Sub-lineages identified by rPinecone in both analyses were phylogenetically robust. It is anticipated that rPinecone can be used to discriminate between lineages of bacteria from LV populations where other methods fail, enabling a deeper understanding of infectious disease epidemiology for public health purposes
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