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Technical document
Global report on infection prevention and control 2024
DOI: 9789240103986
Authors: world health Organization 2024
Abstract
Health care-associated infections (HAIs) affect patients and health systems every day, causing immense suffering, driving higher health-care costs and hampering efforts to achieve high-quality care for all. HAIs are often difficult to treat, are the major driver of antimicrobial resistance (AMR) and cause premature deaths and disability. The COVID-19 pandemic, as well as outbreaks of Ebola, Marburg and mpox are the most dramatic demonstrations of how pathogens can spread rapidly and be amplified in health care settings. But HAIs are a daily threat in every hospital and clinic, not only during epidemics and pandemics. Lack of water, sanitation and hygiene (WASH) in health care settings not only affects the application of infection prevention and control (IPC) best practices but also equity and dignity among both those providing and receiving care. However, there is strong evidence that a large proportion of these infections could be prevented with IPC measures and basic WASH services, with a high return on investment. This second global report on IPC provides updated evidence on the harm caused to patients and health workers by HAIs and AMR, and presents an updated global analysis of the implementation of IPC programmes at the national and health care facility levels across all WHO regions.
Systematic review/Scoping review with large effect size
Mortality in chronic pulmonary aspergillosis: a systematic review and individual patient data meta-analysis
Authors: Abhinav Sengupta et al.,
Abstract
Background: Despite antifungal treatment, chronic pulmonary aspergillosis (CPA) is associated with substantial morbidity and mortality. We conducted a systematic review and meta-analysis to evaluate rates of mortality and its predictors in CPA.
Methods: A systematic literature search was conducted across MEDLINE (PubMed), Scopus, Embase, and Web of Science to identify studies in English, reporting mortality in CPA, from database inception to Aug 15, 2023. We included clinical studies, observational studies, controlled trials, and abstracts. Case reports, animal studies, letters, news, and literature reviews were excluded. Authors of studies published since 2016 were also contacted to obtain anonymised individual patient data (IPD); for other studies, summary estimates were extracted. Subgroup analysis was done for differences in overall 1-year and 5-year mortality, data source, study design, risk of bias, country, Human Development Index, age groups, and the underlying lung disease. We used random-effects meta-analyses to estimate pooled mortality rates. Subgroup analyses and meta-regression were done to explore sources of heterogeneity. One-stage meta-analysis with a stratified Cox proportional hazards model was used to estimate the univariable and hazards for mortality, adjusting for age, sex, type of CPA, treatment, and underlying pulmonary comorbidities. This study was registered with PROSPERO (CRD42023453447).
Findings: We included 79 studies involving 8778 patients in the overall pooled analysis and 15 studies involving 1859 patients in the IPD meta-analysis. Pooled mortality (from 70 studies) was estimated at 27% overall (95% CI 22–32; I2 =95·4%), 15% at 1 year (11–19; I2 =91·6%), and 32% at 5 years (25–39; I2 =94·3%). Overall mortality in patients with CPA with pulmonary tuberculosis as the predominant predisposing condition was 25% (16–35; I2 =87·5%; 20 studies) and with chronic obstructive pulmonary disease was 35% (22–49; I2 =89·7%; 14 studies). Mortality in cohorts of patients who underwent surgical resection was low at 3% (2–4). In the multivariable analysis, among predisposing respiratory conditions, pulmonary tuberculosis history had the lowest mortality hazard (relative to an absence of the disease at baseline), whereas worse outcomes were seen with underlying malignancy; subacute invasive pulmonary aspergillosis and chronic cavitary pulmonary aspergillosis subtypes of CPA were also significantly associated with increased mortality relative to simple aspergilloma on multivariable analysis. Mortality hazard increased by 25% with each decade of age (adjusted hazard ratio 1·25 [95% CI 1·14–1·36], p<0·0001).
Interpretation: CPA is associated with substantial mortality. Advancing age, CPA subtype, and underlying comorbidities are important predictors of mortality. Future studies should focus on identifying appropriate treatment strategies tailored to different risk groups.
Systematic review/Scoping review with large effect size
Prevalence and risk factors for bacteremia in community-acquired pneumonia: a systematic review and meta-analysis
Authors: Shanshan Wu et al.,
Abstract
Highlights
* The incidence of bacteremia in CAP patients was 5.1% (95%CI: 3.6-6.8%)
* The most common pathogen in BC of CAP patients is Streptococcus pneumoniae
* There are various risk factors for bacteremia in CAP patients
Background: Bacteremia represents a significant complication in patients with community-acquired pneumonia (CAP). Nonetheless, there is currently a dearth of systematic research that determines the precise prevalence and risk factors of bacteremia in CAP patients.
Methods: PubMed, Cochrane Library, Embase, and Web of Science databases were searched for published studies on the prevalence or risk factors for CAP with bacteremia up to April 21, 2024. The NOS scale was utilized to appraise the study quality, and the META process was carried out in R language.
Results: 58,342 CAP patients were enrolled in 22 studies. Of these patients, 29,610 underwent blood culture tests, and 2332 patients had positive blood culture results. Meta-analysis pooled results showed that the incidence of bacteremia was 5.1% (95%CI: 3.6-6.8%) in CAP patients. The prevalence of co-bacteremia was 3.1% (95% CI: 1.5-5.1%) in minors and 6.9% (95% CI: 5.2%-8.8%) in adults. The most common pathogens of CAP were Streptococcus pneumoniae, Staphylococcus aureus. In addition, a summary of the original studies found that the risk factors for bacteremia in CAP patients were diverse and varied.
Conclusions: The incidence of bacteremia in CAP patients warrants significant attention. There is a pressing need to establish more specific bacterial screening protocols.
Systematic review/Scoping review with large effect size
Histoplasmosis in cancer patients: A global scoping review (2001–2024)
Authors: Asukwo E. Onukak et al.,
Abstract
Although classified as an AIDS-defining illness, several reports show histoplasmosis also affects patients living with cancers including haematological malignancies and solid tumours. However, reviews describing cases of histoplasmosis in malignancies are lacking in the literature. We identified a total of thirty-four cases with twenty (58.8 %) cases reported from the USA, four from Brazil (11.8 %), three from India (8.8 %), and one each from Singapore (2.9 %), France (2.9 %), Netherlands (2.9 %), Colombia (2.9 %), Canada (2.9 %), Morocco (2.9 %), and Malaysia (2.9 %). 82.4 % (n = 28) of the cases were adults. Presenting symptoms were majorly fever (61.7 %), lymphadenopathy (50.0 %) and weight loss (29.4 %). Essential haematologic findings were pancytopaenia (n = 7, 20.6 %), neutropenia (n = 2, 5.9 %) and anaemia (n = 5, 14.7 %). The associated cancers were predominantly haematological and comprised 73.5 % (n = 25) of all cases. The diagnosis of histoplasmosis was via histopathology (n = 23, 67.6%), culture (n = 13, 38.2%), Histoplasma antigen assay (n = 13, 38.2%), anti-Histoplasma antibody assay (n = 5, 14.7%), PCR and sequencing (n = 2, 5.9%), peripheral blood film/direct microscopy (n = 4, 11.8%) and cytology (n = 1, 2.9%). Of the thirty-four cases, twenty-four (70.6%) had favourable outcomes, eight (23.5%) died, one (2.9%) was lost to follow-up and in one (2.9%) case, the outcome was not stated. Histoplasmosis is not an uncommon opportunistic disease complicating malignancies but is paradoxically underdiagnosed in Africa given the huge burden of cancers in that region. Besides following chemotherapy and the use of steroids, tumour necrosis factor-α antagonists therapy, hematopoietic stem cell transplantation and environmental exposure were factors associated with Histoplasma infection in patients with malignancies. A resolution to promptly screen suspected or confirmed cases of malignancies for histoplasmosis will improve diagnosis and clinical outcomes.
Other
Antiretroviral Drugs for Treatment and Prevention of HIV in Adults: 2024 Recommendations of the International Antiviral Society–USA Panel
Authors: Rajesh T. Gandhi et al.,
Abstract
Importance: New data and new antiretroviral drugs and formulations continue to become available for the prevention and management of HIV infection.
Objective: To provide updated recommendations for HIV treatment and clinical management and HIV prevention.
Methods: A panel of volunteer expert physician scientists were appointed to provide updated consensus recommendations for 2024. Relevant evidence in the literature since the last report was identified from PubMed and Embase searches (which initially yielded 3998 unique citations, of which 249 were considered relevant); from ongoing monitoring of the literature by the panel members; from data submitted by product manufacturers; and from studies presented at peer-reviewed scientific conferences between June 2022 and October 2024.
Findings: Antiretroviral therapy continues to be recommended for all individuals with HIV. For most people with HIV, initial regimens composed of an integrase strand transfer inhibitor (InSTI), specifically bictegravir or dolutegravir, with 2 (and in some cases 1) nucleoside or nucleotide reverse transcriptase inhibitors are recommended. Recommendations are made for those with particular clinical circumstances, such as pregnancy and active opportunistic diseases, as well as for those unable to take InSTIs. Regimens may need to be changed for virologic failure, adverse effects, convenience, or cost, among other reasons. Long-acting injectable therapy is available for those who prefer not to take daily oral medications and for people struggling with adherence to daily therapy. Recommendations are provided for laboratory monitoring, management of substance use disorders and weight changes, as well as use of statins for cardiovascular disease prevention. For HIV prevention, oral (daily or intermittent) and injectable long-acting medications are effective options for people at increased likelihood of HIV exposure. Further, new tools for maintaining health and well-being among people with HIV, such as doxycycline postexposure prophylaxis to avert sexually transmitted infection, and strategies to treat substance use disorders, are recommended. Disparities in HIV acquisition and care access are discussed and solutions proposed.
Conclusions: New approaches for treating and preventing HIV offer additional tools to help end the HIV epidemic, but achieving this goal depends on addressing disparities and inequities in access to care.
Other specific ISP article suggested by Editorial Board
Implementing a healthcare-associated bloodstream infection surveillance network in India: a mixed-methods study on the best practices, challenges and opportunities, 2022
Authors: Srividya K. Vedachalam et al.,
Abstract
Background: Healthcare-associated bloodstream infections (BSI) threaten patient safety and are the third most common healthcare-associated infection (HAI) in low- and middle-income countries. An intensive-care-unit (ICU) based HAI surveillance network recording BSIs was started in India in 2017. We evaluated this surveillance network’s ability to detect BSI to identify best practices, challenges, and opportunities in its implementation.
Methods: We conducted a mixed-methods descriptive study from January to May 2022 using the CDC guidelines for evaluation. We focused on hospitals reporting BSI surveillance data to the HAI network from May 2017 to December 2021, and collected data through interviews, surveys, record reviews, and site visits. We integrated quantitative and qualitative results and present mixed methods interpretation.
Results: The HAI surveillance network included 39 hospitals across 22 states of India. We conducted 13 interviews, four site visits, and one focus-group discussion and collected 50 survey responses. Respondents included network coordinators, surveillance staff, data entry operators, and ICU physicians. Among surveyed staff, 83% rated the case definitions simple to use. Case definitions were correctly applied in 280/284 (98%) case reports. Among 21 site records reviewed, 24% reported using paper-based forms for laboratory reporting. Interviewees reported challenges, including funding, limited human resources, lack of digitalization, variable blood culture practices, and inconsistent information sharing.
Conclusion: Implementing a standardized HAI surveillance network reporting BSIs in India has been successful, and the case definitions developed were simple. Allocating personnel, digitalizing medical records, improving culturing practices, establishing feedback mechanisms, and funding commitment are crucial for its sustainability.
Other specific DSP article suggested by Editorial Board
Positive impact of a diagnostic stewardship intervention on syndromic panel ordering practices and inappropriate C. difficile treatment
DOI: 10.1017/ice.2024.180
Authors: Dan Ilges et al.,
Abstract
Objective: Multiplex polymerase chain reaction (PCR) panels for stool testing may be used to diagnose Clostridioides difficile, which can circumvent more appropriate targeted C. difficile testing, resulting in treatment of incidentally detected colonization. We sought to reduce C. difficile diagnosis via a gastrointestinal pathogen panel (GIPP).
Design: Quasi-experimental, pre/post, retrospective cohort study from January 1, 2022, to January 31, 2024.
Setting: Mayo Clinic Arizona—a single academic medical center and associated clinics.
Patients: Adult patients receiving C. difficile testing and/or treatment.
Methods: Preferred C. difficile testing consisted of glutamate dehydrogenase and toxin antigen immunoassay, followed by toxin gene testing for discrepant results. The GIPP contained 22 targets during the baseline period with C. difficile removed during the postintervention period. Surveys were provided to provider and nursing groups, separately, to identify C. difficile ordering practices and knowledge gaps.
Results: At baseline, from January 1, 2022, to January 31, 2023, 2,772 GIPPs were completed for 2,307 unique patients (∼7 per day), primarily for outpatients (1,805 of 2,772, 65%). The most common positive target was C. difficile (517 of 1,018, 51%), which resulted in treatment for C. difficile infection in 94.9% (337 of 355) of cases. Following GIPP C. difficile target removal, GIPP orders decreased from 3.23 to 2.7 per 1,000 patient visits (P < .001). Prescribing of C. difficile treatments decreased in the postintervention period in inpatient and outpatient settings. There were no cases of delayed C. difficile diagnosis during the postintervention period.
Conclusions: Removing C. difficile from the GIPP resulted in effective diagnostic and antimicrobial stewardship without resulting in delayed diagnoses.
Other specific DSP article suggested by Editorial Board
Say it ain’t Steno: a microbiology nudge comment leads to less treatment of Stenotrophomonas maltophilia respiratory colonization
DOI: 10.1017/ice.2024.195
Authors: Stormmy R. Boettcher et al.,
Abstract
Objective: To describe the effect of a Stenotrophomonas maltophilia (SM) respiratory culture nudge on antibiotic use in colonized patients.
Design: IRB-approved quasi-experiment.
Setting: Five acute-care hospitals in Michigan.
Patients: Adult patients with SM respiratory culture between 01/01/2022 and 01/27/2023 (pre-nudge) and 03/27/2023–12/31/2023 (post-nudge). Patients with active community/hospital/ventilator-acquired pneumonia or who received SM-targeted antibiotics at the time of culture were excluded.
Methods: A nudge comment was implemented 02/2023 stating: “S. maltophilia is a frequent colonizer of the respiratory tract. Clinical correlation for infection is required. Colonizers do not require antibiotic treatment.” The primary outcome was no treatment with SM-therapy; secondary outcomes were treatment with SM-therapy ≥72 hrs, length of stay, and in-hospital, all-cause mortality. Safety outcomes included antibiotic-associated adverse drug events (ADEs).
Results: 94 patients were included: 53 (56.4%) pre- and 41 (43.6%) post-nudge. Most patients were men (53, 56.4%), had underlying lung disease (61, 64.8%), and required invasive ventilatory support (70, 74.5%). Eleven (11.7%) patients resided in a long-term care facility. No treatment with SM therapy was observed in 13 (23.1%) pre- versus 32 (78.0%) post-nudge patients (P <0.001). There were no differences in secondary outcomes. Antibiotic-associated ADEs were common (33/41, 76%) in patients who received ≥72hrs of SM-therapy: fluid overload (18, 44%), hyponatremia (17, 42%), elevated SCr (12, 29%), hyperkalemia (5, 12%). After adjustment for confounders, post-nudge was associated with 11-fold increased odds of no treatment with SM-therapy (adjOR, 11.72; 95%CI, 4.18–32.83).
Conclusions: A targeted SM nudge was associated with a significant reduction in treatment of colonization, with similar patient outcomes. SM-treated patients frequently developed antibiotic-associated ADEs.
Multi-centric observational study with large effect
Rotavirus vaccine effectiveness stratified by national-level characteristics: an introduction to the 24-country MNSSTER-V Project, 2007-2023
Authors: Eleanor Burnett et al.,
Abstract
Background: Rotavirus vaccines are moderately protective against illness in high mortality settings compared with low mortality settings. Vaccine effectiveness (VE) evaluations may clarify our understanding of these disparities, but estimates among key subpopulations and against rare outcomes are not available in many analyses due to sample size. We combined 25 datasets from test-negative design case-control evaluations in 24 countries that enrolled children with medically-attended diarrhea, laboratory-confirmed rotavirus stool testing, and documented vaccination status. We calculated rotavirus VE stratified by country-level characteristics.
Methods: Children 3-59 months old with birthdates and surveillance hospital arrival dates were included; other variables were standardized as available. Children were considered vaccinated if they received ≥1 dose of rotavirus vaccine >14 days before arrival. We summarized child- and country- level characteristics, including national <5-year-old child mortality rate (U5M). Following the manufacturer recommended dose schedule, complete- and partial-series adjusted VE were estimated using logistic regression models.
Results: We included 6,626 rotavirus positive children (cases) and 19,459 rotavirus negative children (controls). Adjusted complete series VE was significantly higher among children from countries in the low and medium U5M strata (74% (95%CI: 64-81)) compared to all groups within the high U5M strata (range: 52% (95%CI: 42- 60) to 46% (95%CI: 31-57)). Partial series were lower than complete series estimates.
Conclusions: These findings are consistent with the published literature, though they suggest heterogeneity in vaccine performance within broad child mortality levels. Our findings also highlight the importance of complete-series vaccination.
Cochrane Database of Systematic Reviews
Interventions to prevent surgical site infection in adults undergoing cardiac surgery
Authors: Cardiothoracic Interdisciplinary Research Network
Abstract
Background: Surgical site infection (SSI) is a common type of hospital‐acquired infection and affects up to a third of patients following surgical procedures. It is associated with significant mortality and morbidity. In the United Kingdom alone, it is estimated to add another £30 million to the cost of adult cardiac surgery. Although generic guidance for SSI prevention exists, this is not specific to adult cardiac surgery. Furthermore, many of the risk factors for SSI are prevalent within the cardiac surgery population. Despite this, there is currently no standard of care for SSI prevention in adults undergoing cardiac surgery throughout the preoperative, intraoperative and postoperative periods of care, with variations in practice existing throughout from risk stratification, decontamination strategies and surveillance.
Objectives: Primary objective: to assess the clinical effectiveness of pre‐, intra‐, and postoperative interventions in the prevention of cardiac SSI. Secondary objectives: (i) to evaluate the effects of SSI prevention interventions on morbidity, mortality, and resource use; (ii) to evaluate the effects of SSI prevention care bundles on morbidity, mortality, and resource use. Search
Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE (Ovid, from inception) and Embase (Ovid, from inception) on 31 May 2021. ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) were also searched for ongoing or unpublished trials on 21 May 2021. No language restrictions were imposed.
Selection criteria: We included RCTs evaluating interventions to reduce SSI in adults (≥ 18 years of age) who have undergone any cardiac surgery. Data collection and analysis: We followed the methods as per our published Cochrane protocol. Our primary outcome was surgical site infection. Our secondary outcomes were all‐cause mortality, reoperation for SSI, hospital length of stay, hospital readmissions for SSI, healthcare costs and cost‐effectiveness, quality of life (QoL), and adverse effects. We used the GRADE approach to assess the certainty of evidence.
Main results: A total of 118 studies involving 51,854 participants were included. Twenty‐two interventions to reduce SSI in adults undergoing cardiac surgery were identified. The risk of bias was judged to be high in the majority of studies. There was heterogeneity in the study populations and interventions; consequently, meta‐analysis was not appropriate for many of the comparisons and these are presented as narrative summaries. We focused our reporting of findings on four comparisons deemed to be of great clinical relevance by all review authors.
Decolonisation versus no decolonisation: Pooled data from three studies (n = 1564) using preoperative topical oral/nasal decontamination in all patients demonstrated an uncertain direction of treatment effect in relation to total SSI (RR 0.98, 95% CI 0.70 to 1.36; I2 = 0%; very low‐certainty evidence). A single study reported that decolonisation likely results in little to no difference in superficial SSI (RR 1.35, 95% CI 0.84 to 2.15; moderate‐certainty evidence) and a reduction in deep SSI (RR 0.36, 95% CI 0.17 to 0.77; high‐certainty evidence).
The evidence on all‐cause mortality from three studies (n = 1564) is very uncertain (RR 0.66, 95% CI 0.24 to 1.84; I2 = 49%; very low‐certainty evidence).
A single study (n = 954) demonstrated that decolonisation may result in little to no difference in hospital readmission for SSI (RR 0.80, 95% CI 0.44 to 1.45; low‐certainty evidence).
A single study (n = 954) reported one case of temporary discolouration of teeth in the decolonisation arm (low‐certainty‐evidence.
Reoperation for SSI was not reported.
Tight glucose control versus standard glucose control
Pooled data from seven studies (n = 880) showed that tight glucose control may reduce total SSI, but the evidence is very uncertain (RR 0.41, 95% CI 0.19 to 0.85; I2 = 29%; numbers need to treat to benefit (NNTB) = 13; very‐low certainty evidence).
Pooled data from seven studies (n = 3334) showed tight glucose control may reduce all‐cause mortality, but the evidence is very uncertain (RR 0.61, 95% CI 0.41 to 0.91; I2 = 0%; very low‐certainty evidence).
Based on four studies (n = 2793), there may be little to no difference in episodes of hypoglycaemia between tight control vs. standard control, but the evidence is very uncertain (RR 2.12, 95% CI 0.51 to 8.76; I2 = 72%; very low‐certainty evidence).
No studies reported superficial/deep SSI, reoperation for SSI, or hospital readmission for SSI.
Negative pressure wound therapy (NPWT) versus standard dressings
NPWT was assessed in two studies (n = 144) and it may reduce total SSI, but the evidence is very uncertain (RR 0.17, 95% CI 0.03 to 0.97; I2 = 0%; NNTB = 10; very low‐certainty evidence).
A single study (n = 80) reported reoperation for SSI. The relative effect could not be estimated. The certainty of evidence was judged to be very low.
No studies reported superficial/deep SSI, all‐cause mortality, hospital readmission for SSI, or adverse effects.
Topical antimicrobials versus no topical antimicrobials
Five studies (n = 5382) evaluated topical gentamicin sponge, which may reduce total SSI (RR 0.62, 95% CI 0.46 to 0.84; I2 = 48%; NNTB = 32), superficial SSI (RR 0.60, 95% CI 0.37 to 0.98; I2 = 69%), and deep SSI (RR 0.67, 95% CI 0.47 to 0.96; I2 = 5%; low‐certainty evidence.
Four studies (n = 4662) demonstrated that topical gentamicin sponge may result in little to no difference in all‐cause mortality, but the evidence is very uncertain (RR 0.96, 95% CI 0.65 to 1.42; I2 = 0%; very low‐certainty evidence).
Reoperation for SSI, hospital readmission for SSI, and adverse effects were not reported in any included studies.
Authors’ conclusions: This review provides the broadest and most recent review of the current evidence base for interventions to reduce SSI in adults undergoing cardiac surgery. Twenty‐one interventions were identified across the perioperative period. Evidence is of low to very low certainty primarily due to significant heterogeneity in how interventions were implemented and the definitions of SSI used. Knowledge gaps have been identified across a number of practices that should represent key areas for future research. Efforts to standardise SSI outcome reporting are warranted.
Cochrane Database of Systematic Reviews
Serum and urine nucleic acid screening tests for BK polyomavirus‐associated nephropathy in kidney and kidney‐pancreas transplant recipients
Authors: Thida Maung Myint et al.,
Abstract
Background: BK polyomavirus‐associated nephropathy (BKPyVAN) occurs when BK polyomavirus (BKPyV) affects a transplanted kidney, leading to an initial injury characterised by cytopathic damage, inflammation, and fibrosis. BKPyVAN may cause permanent loss of graft function and premature graft loss. Early detection gives clinicians an opportunity to intervene by timely reduction in immunosuppression to reduce adverse graft outcomes. Quantitative nucleic acid testing (QNAT) for detection of BKPyV DNA in blood and urine is increasingly used as a screening test as diagnosis of BKPyVAN by kidney biopsy is invasive and associated with procedural risks. In this review, we assessed the sensitivity and specificity of QNAT tests in patients with BKPyVAN.
Objectives: We assessed the diagnostic test accuracy of blood/plasma/serum BKPyV QNAT and urine BKPyV QNAT for the diagnosis of BKPyVAN after transplantation. We also investigated the following sources of heterogeneity: types and quality of studies, era of publication, various thresholds of BKPyV‐DNAemia/BKPyV viruria and variability between assays as secondary objectives.
Search methods: We searched MEDLINE (OvidSP), EMBASE (OvidSP), and BIOSIS, and requested a search of the Cochrane Register of diagnostic test accuracy studies from inception to 13 June 2023. We also searched ClinicalTrials.com and the WHO International Clinical Trials Registry Platform for ongoing trials.
Selection criteria: We included cross‐sectional or cohort studies assessing the diagnostic accuracy of two index tests (blood/plasma/serum BKPyV QNAT or urine BKPyV QNAT) for the diagnosis of BKPyVAN, as verified by the reference standard (histopathology). Both retrospective and prospective cohort studies were included. We did not include case reports and case control studies.
Data collection and analysis: Two authors independently carried out data extraction from each study. We assessed the methodological quality of the included studies by using Quality Assessment of Diagnostic‐Accuracy Studies (QUADAS‐2) assessment criteria. We used the bivariate random‐effects model to obtain summary estimates of sensitivity and specificity for the QNAT test with one positivity threshold. In cases where meta‐analyses were not possible due to the small number of studies available, we detailed the descriptive evidence and used a summative approach. We explored possible sources of heterogeneity by adding covariates to meta‐regression models.
Main results: We included 31 relevant studies with a total of 6559 participants in this review. Twenty‐six studies included kidney transplant recipients, four studies included kidney and kidney‐pancreas transplant recipients, and one study included kidney, kidney‐pancreas and kidney‐liver transplant recipients. Studies were carried out in South Asia and the Asia‐Pacific region (12 studies), North America (9 studies), Europe (8 studies), and South America (2 studies).
Index test: blood/serum/plasma BKPyV QNAT
The diagnostic performance of blood BKPyV QNAT using a common viral load threshold of 10,000 copies/mL was reported in 18 studies (3434 participants). Summary estimates at 10,000 copies/mL as a cut‐off indicated that the pooled sensitivity was 0.86 (95% confidence interval (CI) 0.78 to 0.93) while the pooled specificity was 0.95 (95% CI 0.91 to 0.97). A limited number of studies were available to analyse the summary estimates for individual viral load thresholds other than 10,000 copies/mL. Indirect comparison of thresholds of the three different cut‐off values of 1000 copies/mL (9 studies), 5000 copies/mL (6 studies), and 10,000 copies/mL (18 studies), the higher cut‐off value at 10,000 copies/mL corresponded to higher specificity with lower sensitivity. The summary estimates of indirect comparison of thresholds above 10,000 copies/mL were uncertain, primarily due to a limited number of studies with wide CIs contributed to the analysis. Nonetheless, these indirect comparisons should be interpreted cautiously since differences in study design, patient populations, and methodological variations among the included studies can introduce biases. Analysis of all blood BKPyV QNAT studies, including various blood viral load thresholds (30 studies, 5658 participants, 7 thresholds), indicated that test performance remains robust, pooled sensitivity 0.90 (95% CI 0.85 to 0.94) and specificity 0.93 (95% CI 0.91 to 0.95). In the multiple cut‐off model, including the various thresholds generating a single curve, the optimal cut‐off was around 2000 copies/mL, sensitivity of 0.89 (95% CI 0.66 to 0.97) and specificity of 0.88 (95% CI 0.80 to 0.93). However, as most of the included studies were retrospective, and not all participants underwent the reference standard tests, this may result in a high risk of selection and verification bias.
Index test: urine BKPyV QNAT
There was insufficient data to thoroughly investigate both accuracy and thresholds of urine BKPyV QNAT resulting in an imprecise estimation of its accuracy based on the available evidence.
Authors’ conclusions: There is insufficient evidence to suggest the use of urine BKPyV QNAT as the primary screening tool for BKPyVAN. The summary estimates of the test sensitivity and specificity of blood/serum/plasma BKPyV QNAT test at a threshold of 10,000 copies/mL for BKPyVAN were 0.86 (95% CI 0.78 to 0.93) and 0.95 (95% CI 0.91 to 0.97), respectively. The multiple cut‐off model showed that the optimal cut‐off was around 2000 copies/mL, with test sensitivity of 0.89 (95% CI 0.66 to 0.97) and specificity of 0.88 (95% CI 0.80 to 0.93). While 10,000 copies/mL is the most commonly used cut‐off, with good test performance characteristics and supports the current recommendations, it is important to interpret the results with caution because of low‐certainty evidence.