Diagnosis of Infectious Diseases

Accurate diagnostic tests are fundamental in the quality of care and to establish the best outcome for patients and the wider population. Despite continued advances in diagnostic technologies, many patients are still undiagnosed or mis-diagnosed which can lead to ineffective management, treatments, and poor outcomes. There is a continual need to improve the complete patient and sample pathway, including pre-analytical decision making, analytical technologies, and post-analytical interpretation and decision making. Novel tests that can identify a specific pathogen or at a minimum, distinguish between different types of bacterial, viral, parasitic or fungal infections, and ideally provide information on ways to effectively treat are becoming increasingly prevalent. This continual improvement leads to improvements in clinical outcomes for patients, effective treatment stewardship, detection and tracking of disease outbreaks, and investigation of unknown pathogens. Moreover, the improvement of regulatory systems and quality practices ensures the sustainability in the progression of improvement practices.
The Microbiology Society’s Journal of Medical Microbiology has collaborated with the Association for Laboratory Medicine to create this special collection on Diagnosis of Infectious Diseases. In this collection, we provide insightful and impactful articles highlighting a wide range of areas contributing to the continual development of better diagnostic pathways in infection, from novel technical advances and quality systems to the importance of effective infrastructure and leadership.
This collection aims to showcase the breadth, complexity, and importance of diagnostics in infectious diseases and public health, including to a non-specialist audience.
Editors: Rob Shorten and Mathew Diggle
Status: Closed for submissions
Photo credit: iStock/ Md Saiful Islam Khan
Collection Contents
9 results
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Overview of US public health laboratory leadership development programmes and implementation opportunities
More LessIntroduction. The public health laboratory system in the United States (USA) is extensive and focuses on the health of the nation’s population by providing testing for the identification and spread mitigation of public health concerns. Testing for communicable diseases, antimicrobial resistance, per- and polyfluoroalkyl substances, and much more is performed on human, animal and environmental specimens by federal, state and local level public health laboratories.
Gap Statement. Unique challenges exist for public health laboratory professionals, and individuals in this field are commonly appointed to leadership positions without any formal leadership or management training.
Aim. The authors aim to identify potential challenges for public health laboratory leaders and suggest how leaders may successfully navigate them. Additionally, this article aims to expand awareness of federally funded public health laboratory leadership programmes in the United States and when they may be applicable for prospective or current leaders.
Methodology. The authors reviewed publications and presentations to determine successful and unsuccessful leadership attributes in a public health laboratory context. They assessed federally funded leadership programmes in the USA via publications and publicly available information and interviewed select individuals who participated in or assisted in the development of these programmes.
Results. Six common challenges for public health laboratory leaders were identified and potential solutions are suggested. The Centers for Disease Control and Prevention (CDC) and the Association of Public Health Laboratories (APHL) provide four unique laboratory leadership training programmes for laboratorians interested in or currently employed within public health laboratories.
Conclusion. While the content of the federally funded programmes is different, they all aim to provide current and future public health laboratory leaders with the skills that they need to effectively guide and support laboratory staff through the critical and intense situations that public health laboratories commonly face.
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Parasitology of the twenty-first century: are we moving in the right direction?
More LessFor thousands of years, parasitic infections have represented a constant challenge to human health. Despite constant progress in science and medicine, the challenge has remained mostly unchanged over the years, partly due to the vast complexity of the host–parasite–environment relationships. Over the last century, our approaches to these challenges have evolved through considerable advances in science and technology, offering new and better solutions. Unfortunately, in the twenty-first century, this diagnostic evolution was suddenly confronted with a dramatic change of biological relationships, never witnessed in history before the uncontrolled expansion of the human population, globalization and hyperconnectivity technology have exerted a massive socioeconomic impact on individuals, communities and the environment, sending a ripple effect throughout the world of parasites. Urbanization, pollution and the unsustainable exploitation of natural resources have caused shifts in biomass and the fragmentation of habitats, leading to the movement of parasites into new hosts and territories. At the same time, changes in human population structure and distributions due to armed conflict and poverty created massive migration of entire nations and communities, resulting in the redistribution of parasitic diseases. To make the situation worse, the population of many receiving countries of North America and Europe is ageing, leading to a critical shortage of a specialized workforce essential to deal with the new diagnostic challenges. Unfortunately, this vicious circle is not yet apparent to all. The highly specialized field of parasitology is at a particular risk for such major crises in the near future. Heightened awareness of such risks is an essential step to start discussions and planning to mitigate these very real health threats.
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Chronic Strongyloides stercoralis infection in Fijian migrants to the UK
More LessWilliam D. Nevin, Jake Melhuish, Jayne Jones, Lucas Cunningham, James Dodd, Romeo Toriro, Matthew Routledge, Luke Swithenbank, Thomas D. Troth, Stephen D. Woolley, Angela Fountain, Claire Hennessy, Simon A. Foster, Charlotte Hughes, Mark R. Riley, Simran Rai, Russell Stothard, Edward D. Nicol, Mark Dermont, Duncan Wilson, David Woods, Lucy Lamb, Matthew K. O'Shea, Nicholas J. Beeching and Thomas FletcherIntroduction. Strongyloides stercoralis, the human threadworm, is a parasitic nematode with global distribution, estimated to infect over 600 million people. Chronic infection is often asymptomatic, but hyperinfection and dissemination syndromes can occur in the immunosuppressed with high case fatality rates. Whilst strongyloidiasis is endemic in Fiji, its prevalence in Fijian migrant groups in the UK is unknown.
Gap Statement. No previous studies have been conducted on the prevalence of Strongyloides and other gastrointestinal parasites (GIPs) in Fijian migrants to the UK.
Aim. We conducted a cross-sectional study of the prevalence of GIPs in a Fijian migrant population.
Methodology. Participants completed a questionnaire on residence, travel and clinical symptoms and were asked to provide a serum sample for S. stercoralis IgG ELISA, venous blood samples for eosinophil count and a faecal sample for charcoal culture, multiplex real-time PCR (rtPCR) and microscopy after formalin-ethyl acetate concentration. Sequencing was performed on pooled Strongyloides larvae for nuclear 18S rRNA hyper-variable regions (HVRs) I and IV.
Results. A total of 250 participants (94% male) with median (range) age 37 (20–51) years entered the study, 15 (1–24) years since leaving Fiji. S. stercoralis IgG ELISA was positive in 87/248 (35.1 %) and 14/74 (18.9 %) had a GIP detected in faeces. This included 7/74 (9.5 %) with Strongyloides and 5/74 (6.8 %) with hookworms. Dermatological symptoms were more common in those with Strongyloides, and eosinophilia (>0.5×109 cells per litre) was present in 55.6% of those with positive S. stercoralis IgG. rtPCR was the most sensitive faecal diagnostic test for Strongyloides and hookworms in faeces. Sequences of nuclear 18S rRNA for HVRs I and IV confirmed the presence of S. stercoralis.
Conclusion. This first cross-sectional study in Fijian migrants found a high rate of chronic infection with GIPs, particularly S. stercoralis. Faecal microscopy was insensitive compared to charcoal culture, rtPCR or serology, demonstrating the importance of specialist parasitological tests when investigating people with a suspected chronic infection. Our study highlights an overlooked burden of strongyloidiasis in the UK and has implications for screening and treatment programmes in Fiji and for migrants from Fiji.
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Identification methods as a factor affecting the performance of clinical microbiology laboratories participating in an external quality assessment program: a cross-sectional, retrospective analysis
More LessIntroduction. Laboratory participation in external quality assessment (EQA) programmes including proficiency testing (PT) is a requirement of clinical laboratory conformance to ISO 15189:2022 Medical laboratories – Requirements for quality and competence. PT is one EQA method whereby laboratories are sent blinded samples for characterization by routine laboratory diagnostic methods. Importantly, PT enables a laboratory’s performance to be evaluated in comparison to the standard reference methods and to the performance of other peer laboratories using similar diagnostic methods.
Gap statement. The desired outcome of participating in PT is to help laboratories identify possible sources of error in each step of the total testing process and particularly in their test methods during the analytical phase.
Aim. This cross-sectional study investigated the impact of using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) compared to conventional phenotypic biochemical testing on laboratory performance in a clinical bacteriology PT scheme.
Methodology. During a 6-year period from 2017-2022, the Canadian Microbiology Proficiency Testing implemented 112 PT challenges comprising 22 different sample types and included 61 different bacterial species. This was translated into 5883 graded test events for analysis. Multiple logistic regression techniques were employed to explore the association between the test method employed and laboratory performance. The sample type and aerobic classification of challenge organisms were included as confounding variables.
Results. Laboratories using MALDI-TOF MS performed significantly better in characterizing microorganisms than laboratories using phenotypic biochemical testing alone [odds ratio OR = 5.68, confidence interval (CI): 3.92, 8.22] regardless of the sample type and aerobic classification. Notably, our analysis identified a significant association between anaerobic organisms and laboratory performance (OR: 0.24, CI: 0.17–0.35), suggesting that culturing and identifying fastidious organisms remains a significant obstacle for many clinical microbiology laboratories.
Conclusions. Although no method is infallible and its performance will depend on the validation and quality assurance procedures, this finding may help the management in the decision for implementing MALDI-TOF MS in the microbiology laboratory. This study highlights the important role PT providers play in the objective assessment of laboratory performance and how it can provide evidence for quality improvement.
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Combining Gram stain and 16S qPCR improved diagnostic accuracy for suspected pneumonia and could become a new metric in the rapid diagnosis of lower respiratory tract infections
More LessYunas Panikkaveettil Hamza, Mohamed Ali Ben Hadj Kacem, Naema Hassan Al Molawi, Hadi Mohamad Yassine, Hebah Atef Mohammad AlKhatib, Fatiha Benslimane, Hanan Ibrahim Kh. B. Al-Remaihi, Reham Awni El Kahlout, Basema Ibrahim Ahmed El Kahlout, Hajar Al Khalili, Makiyeh Ahmed Al Khalili, Sanjay H. Doiphode, Emad Bashier Ibrahim Elmagboul, Javed Akhter, Einas A/Aziz Eid Al Kuwari and Peter V. CoyleIntroduction. The frequency of multidrug-resistant organisms (MDROs) in hospitals and the risk of delaying effective treatment result in the culture of respiratory secretions for nearly all patients with suspected pneumonia. Culture delays contribute to over prescribing and use of broader spectrum antibiotics.
Gap statement. The need for improved rapid diagnostics for early assessment of suspected hospital pneumonia.
Aim. To validate a new metric, enhanced Gram stain (EGS), to provide a rapid diagnostic test of high diagnostic accuracy that could be assessed in clinical trials of the use of antibiotics in suspected pneumonia.
Methodology. Ninety-two residual lower respiratory samples previously tested by culture and Gram stain were re-tested by 16S ribosomal DNA real-time polymerase chain reaction (16S qPCR) and reported as a combined metric with Gram stain termed EGS. The EGS was assessed for diagnostic accuracy, standard performance measurements and correlation against culture. For samples with discordance between culture and EGS, 16S ribosomal DNA whole operon sequencing (16S rDNA WOS) was used for test resolution. An amended EGS (A-EGS was reassessed against culture.
Results. Gram stain, 16S qPCR, EGS and A-EGS had respective diagnostic accuracies of 77.01 %, 82.76 %, 84.04 % and 94.19 %. The same platforms had respective correlation with culture of r = 0.67, r = 0.71, r = 0.81 and r = 0.89. EGS had the highest negative predictive value (NPV) of 93.18 % (81.99 %–97.62 %). Adding an 16S qPCR result is achievable in most routine laboratories and, combined with Gram stain, could improve early decision-making in patients with suspected hospital pneumonia.
Conclusion. EGS could improve early decision-making in patients with suspected hospital pneumonia and could be assessed in clinical trials. The 16S rDNA WOS results in the A-EGS also supported the use of pathogen genomic sequencing in early decision making of suspected pneumonia.
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Building an antimicrobial stewardship model for a public-sector hospital: a pre-implementation study
More LessIntroduction. Antimicrobial resistance (AMR) is recognized as an important global health risk, associated with increased mortality, morbidity and healthcare costs. Antimicrobial stewardship (AMS) involves a coherent set of processes that promote the rational use of antimicrobials.
Gap statement. An AMS programme should be adapted and developed according to the available resources of a facility. This requires an analysis of the core AMS elements that are already in place and the resources available.
Aim. This study aimed to assess the readiness of a tertiary healthcare facility and staff towards implementing an antimicrobial stewardship programme (ASP).
Methodology. This study focused on two aspects during an AMS pre-implementation phase. A situational or strengths, weaknesses, opportunities, and threats analysis was conducted based on (1) a questionnaire on attitudes and perceptions of pharmacists, clinicians and nurses towards AMR and AMS and (2) a situational analysis on the readiness of the facility.
Results. The questionnaire, which was available for completion between September 2021 and December 2021, was sent to a total of 3100 healthcare professionals (HCPs). Thirty-two (1.0 %) HCPs comprising 2 pharmacists, 16 clinicians and 14 nurses completed the questionnaire. Of the total participants, 31 (96.9 %) viewed AMR as a problem in South African hospitals and 29 (90.6 %) perceived AMR as a problem at their facility. The majority (n = 29, 90.6 %) of the participants were familiar with the term AMS, and 26 (81.3 %) participants agreed to willingly participate in any initiatives involving antimicrobial use at the facility. The situational analysis depicted existing strengths in terms of AMS structures such as the formation of an AMS committee and information and technology systems at the HCP’s disposal. Weaknesses included the limited number of AMS activities being carried out and poor participation from HCPs within the AMS team.
Conclusion. A pre-implementation phase in the building of an ASP can greatly assist in finding gaps for improvement, which can then be addressed in the implementation phase. Furthermore, the pre-implementation phase provides a baseline to measure improvements once the implementation phase has been instituted.
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Diagnostic stewardship in infectious diseases: a scoping review
More LessIntroduction. The term ‘diagnostic stewardship’ is relatively new, with a recent surge in its use within the literature. Despite its increasing popularity, a precise definition remains elusive. Various attempts have been made to define it, with some viewing it as an integral part of antimicrobial stewardship. The World Health Organization offers a broad definition, emphasizing the importance of timely, accurate diagnostics. However, inconsistencies in the use of this term still persist, necessitating further clarification.
Gap Statement. There are currently inconsistencies in the definition of diagnostic stewardship used within the academic literature.
Aim. This scoping review aims to categorize the use of diagnostic stewardship approaches and define this approach by identifying common characteristics and factors of its use within the literature.
Methodology. This scoping review undertook a multi-database search from date of inception until October 2022. Any observational or experimental study where the authors define the intervention to be diagnostic stewardship from any clinical area was included. Screening of all papers was undertaken by a single reviewer with 10% verification by a second reviewer. Data extraction was undertaken by a single reviewer using a pre-piloted form. Given the wide variation in study design and intervention outcomes, a narrative synthesis approach was applied. Studies were clustered around common diagnostic stewardship interventions where appropriate.
Results. After duplicate removal, a total of 1310 citations were identified, of which, after full-paper screening, 105 studies were included in this scoping review. The classification of an intervention as taking a diagnostic stewardship approach is a relatively recent development, with the first publication in this field dating back to 2017. The majority of research in this area has been conducted within the USA, with very few studies undertaken outside this region. Visual inspection of the citation map reveals that the current evidence base is interconnected, with frequent references to each other’s work. The interventions commonly adopt a restrictive approach, utilizing hard and soft stops within the pre-analytical phase to restrict access to testing. Upon closer examination of the outcomes, it becomes evident that there is a predominant focus on reducing the number of tests rather than enhancing the current test protocol. This is further reflected in the limited number of studies that report on test performance (including protocol improvements, specificity and sensitivity).
Conclusion. Diagnostic stewardship seems to have deviated from its intended course, morphing into a rather rudimentary instrument wielded not to enhance but to constrict the scope of testing. Despite the World Health Organization’s advocacy for an ideology that promotes a more comprehensive approach to quality improvement, it may be more appropriate to consider alternative regional narratives when categorizing these types of quality improvement interventions.
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