Undifferentiated Illness Research Articles

Clinical approach to donor-derived infection in solid organ transplant recipients.

Donor-derived infection is an uncommon but potentially devastating complication of solid organ transplantation (SOT). Accurate and timely identification of unexpected infectious disease transmission events has implications not only for the recipient(s) experiencing infection, but also other recipients of organs or tissues from the same donor who may require additional testing or risk mitigation, as well as the broader organ transplant regulatory framework. This narrative review synthesizes data from published reports of symptomatic unexpected donor-derived infections in SOT recipients to provide clinicians with a systematic approach to the evaluation of undifferentiated illnesses that may be of donor origin. Key reasons to consider donor-derived infection include certain microbiologically proven infections in the recipient, especially early after transplant, characteristics of the donor or their management that suggest potential exposure to or infection with specific pathogens prior to organ procurement, and select clinical syndromes that occur in the post-transplant period. Syndromes for which expedited consideration and evaluation of donor-derived infection may be warranted include central nervous system infection, graft or perigraft complications developing in the absence of typical risk factors, and unexplained critical illness/sepsis syndrome in the early post-transplant period. When embarking on an investigation of a suspected donor-derived infection, clinicians should apply knowledge of the entire continuum of the organ procurement and transplant process to ensure unbiased and comprehensive data collection that will facilitate appropriate adjudication of these uncommon but high-consequence events.

Early Physician Gestalt Versus Usual Screening Tools for the Prediction of Sepsis in Critically Ill Emergency Patients

ObjectiveCompare physician gestalt to existing screening tools for the identification of sepsis in the initial minutes of presentation when time sensitive treatments must be initiated. MethodsThis prospective observational study conducted with consecutive encounter sampling took place in the emergency department of an academic, urban, safety net hospital between September 2020 and May 2022. The study population included critically ill emergency department patients excluding traumas, transfers, and self-evident diagnoses. Emergency physician gestalt was measured using a visual analog scale (VAS) from 0-100 at 15 and 60 minutes after patient arrival. The primary outcome was an explicit sepsis hospital discharge diagnosis. Clinical data were recorded up to 3 hours to compare Systemic Inflammatory Response Syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), quick SOFA (qSOFA), Modified Early Warning Score (MEWS) and a logistic regression machine learning model utilizing Least Absolute Shrinkage and Selection Operator (LASSO) for variable selection. The screening tools were compared utilizing ROC analysis and calculation of AUC. Results2,484 patient-physician encounters involving 59 attending physicians were analyzed. 275 patients (11%) received an explicit sepsis discharge diagnosis. When limited to available data at 15 minutes, initial VAS (AUC 0.90; 95% CI 0.88-0.92) outperformed all tools including LASSO (0.84, 95% CI 0.82-0.87), qSOFA (0.67; 95% CI 0.64-0.71), SIRS (0.67; 95% 0.64-0.70), SOFA (0.67; 95% CI 0.63-0.70) and MEWS (0.66; 95% CI 0.64-0.69). Expanding to data available at 60 minutes did not meaningfully change results. ConclusionsAmong adults presenting to an emergency department with an undifferentiated critical illness, physician gestalt in the first 15 minutes of the encounter outperformed other screening methods in identifying sepsis.

Review on Scrub Typhus: An Important Etiology of Acute Undifferentiated Fever Illness.

One of India's predominant public health issues is acute undifferentiated fever illness (AUFI), a typical response to an infectious agent. Diagnosisbecomes challenging when the disease has been reported with fever as the primary symptom. Among thecases presenting at a tertiary care hospitalin central India, 88% had an acute undifferentiated fever, the most common being dengue infection. In India, rural communities are at more risk from AUFI than cities. Most of those in danger are those who reside in remote areas, and one of the most significant risksis for those who reside close toforests. AUFI is a complex condition for physicians to deal with and is one of the most frequent clinical conditions for which empirical treatment is required. Nowadays, AUFI can be managed by a syndromic approach with the judicial use of antibiotics. Symptoms of AUFI, along with myalgia, headache, and anorexia, can be caused by various illnesses. Patients are recommended to undertake a battery of investigations, which may delay the therapy and increase expenses because many diseases may present with the same symptoms. In the developed world, viral illness is the primary cause of AUFI. However, in developing countries like India, it can also be brought on by potentially curable but life-threatening conditions such as malaria, leptospirosis, hantavirus infection, and Japanese encephalitis. Lack of knowledge of the locally prevalent illnesses, which might be the causeof AUFI, and lack of preliminary screening and diagnostics at the point of care to identify the etiologies make it difficult to control these generally curable causes of the burden of AUFI, especially in tropical and subtropical countries. A deeper understanding of AUFI is required to develop better diagnostics and cures for various etiologies, especially scrub typhus.

A study on acute undifferentiated febrile illness in children (Age 2 Months to 18 Years)

: Acute Undifferentiated Febrile Illness (AUFI) is a common cause of patients seeking healthcare in India. Appropriate diagnosis is essential for proper management of children, since failure to identify the nature of the causative pathogen results in increased morbidity and mortality due to diseases either being untreated or treated with inappropriate antimicrobials, Also there is waste of medicines and increased resistance to antimicrobials, which has a major public health threat worldwide.: To study clinical profile of children admitted with AUFI and to find out common causes of AUFI in Children (2 months to 18 years of age) and their seasonal trends. : A prospective study was carried out over 200 children of age 2 months to 18 months admitted in Balchikitsalaya MBGH Hospital with Acute Undifferentiated Febrile Illness of less than 7 days duration over a period of 12 months from November 2021 to October 2022. : Majority of the patients were in the age group of 10-15 years (32.5%). Out of 200 AUFI patients, majority had undifferentiated illness (53%) followed by Malaria (16.5%), UTI (12.5%), Dengue(11%), Scrub Typhus(5%) and Enteric Fever(2.5%). Higher incidence of AUFI was seen from August to November. : More than 50% cases of Acute Febrile Illness were due to Undifferentiated Illnesses, hence it can be concluded that provided the cause of undifferentiated illness is found, the irrational use of antibiotics and antimalarial should be prevented.

The seasonality of infections in tropical Far North Queensland, Australia: A 21-year retrospective evaluation of the seasonal patterns of six endemic pathogens.

An understanding of the seasonality of infections informs public health strategies and assists clinicians in their management of patients with undifferentiated illness. The seasonality of infections is driven by a variety of environmental and human factors; however, the role of individual climatic factors has garnered much attention. This study utilises Poisson regression models to assess the seasonality of six important infections in tropical Australia and their association with climatic factors and severe weather events over a 21-year period. Melioidosis and leptospirosis showed marked wet season predominance, while more cases of rickettsial disease and cryptococcosis were seen in cooler, drier months. Staphylococcus aureus infections were not seasonal, while influenza demonstrated inter-seasonality. The climate did not significantly change during the 21 years of the study period, but the incidence of melioidosis and rickettsial disease increased considerably, highlighting the primacy of other factors-including societal inequality, and the impact of urban expansion-in the incidence of these infections. While anthropogenic climate change poses a threat to the region-and may influence the burden of these infections in the future-this study highlights the fact that, even for seasonal diseases, other factors presently have a greater effect on disease incidence. Public health strategies must also target these broader drivers of infection if they are to be effective.

Etiology and clinical spectrum of acute undifferentiated fever illness in patients in a tertiary care hospital Sheri Kashmir institute of medical science Soura, Jammu and Kashmir

Background: Current study aimed at s to delineate the etiology and clinical parameters associated with AUFI presenting to emergency department in a tertiary care hospital.Methods: This was a prospective hospital based study carried out at emergency medicine, SKIMS hospital, Soura Kashmir, India July 2017 to august 2018. Patients with acute undifferentiated fever were enrolled. Descriptive statistics were calculated in terms of mean±SD for continuous variables like age of the patients and duration of fever, Frequency and percentage were used to analyse categorical variables such as causes of fever and gender, while as descriptive analysis was calculated in terms of mean±SD for continuous variables like age of the patients and duration of fever.Results: Total numbers of patients included were 174, among these 112 (64.3%) were males and 62 (35.6%) were females. Most patients were diagnosed enteric fever (N=59, 33.9%) followed by UTI (N=25, 14.3%) dengue (N=12, 6.8%) and malaria (N=8, 4.5%) while rest of cases were associated with other viral illnesses (N=70, 40.5%) based on clinical basis and inconclusive laboratory results.Conclusions: Enteric fever was found to be the most common cause of acute undifferentiated fever followed by dengue and other viral illnesses, although causes and clinic spectrum of AUFI is varied.

Study of aetiology and clinical spectrum of patients with acute undifferentiated fever, in a tertiary care setting: a descriptive cross-sectional study

Background: Acute undifferentiated fever illness (AUFI) is a common cause of morbidity and mortality in developing countries, owing to its non-specific features. The aim of the study was to delineate the causes and clinical parameters associated with AUFI.Methods: A cross-sectional study was done among 156 patients of AUFI, admitted in the Department of Medicine, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India, from November 2018 to October 2019.Results: The mean age of the study participants was 37.37±14.2 years. The study participants admitted for acute undifferentiated febrile illness had fever with mean duration of 8.38±3.7 days before hospitalization. The most common aetiology of AUFI was found to be enteric fever (44%), followed by scrub typhus (35%). The majority of the cases presented from the month of September to December.Conclusions: The aetiology and clinical spectrum of AUFI is wide and variable. To outline a proper algorithm to contain it, meticulous analysis of the hospital data at each level is necessary.

Is the NICE traffic light system fit-for-purpose for children presenting with undifferentiated acute illness in primary care?

BackgroundThe National Institute of Clinical Excellence (NICE) traffic light system uses children’s symptoms and signs to categorise acute infections into red, amber and green. To our knowledge, no study has...

Clinical Features of Acute Chikungunya Virus Infection in Children and Adults during an Outbreak in the Maldives.

ABSTRACT.The chikungunya virus is an arthritogenic arbovirus that has re-emerged in many tropical and subtropical regions, causing explosive outbreaks. This re-emergence is due to a genomic polymorphism that has increased the vector susceptibility of the virus. The majority of those infected with chikungunya virus exhibit symptoms of fever, rash, and debilitating polyarthralgia or arthritis. Symptoms can persist for weeks, and patients can relapse months later. Fatalities are rare, but individuals of extreme age can develop severe infection. Here, we describe the 2019 outbreak, the second-largest since the virus re-emerged in the Maldives after the 2004 Indian Ocean epidemic, in which a total of 1,470 cases were reported to the Health Ministry. Sixty-seven patients presenting at the main referral tertiary care hospital in the Maldives capital with acute undifferentiated illness were recruited following a negative dengue serology. A novel point-of-care antigen kit was used to screen suspected cases, 50 of which were subsequently confirmed using real-time reverse transcription–polymerase chain reaction. We describe the genotype and polymorphism of Maldives chikungunya virus using phylogenetic analysis. All isolates were consistent with the East Central South African genotype of the Indian Ocean lineage, with a specific E1-K211E mutation. In addition, we explored the clinical and laboratory manifestations of acute chikungunya in children and adults, of which severe infection was found in some children, whereas arthritis primarily occurred in adults. Arthritides in adults occurred irrespective of underlying comorbidities and were associated with the degree of viremia.

Perceptions and beliefs about the regulation of advanced nurse practitioners.

The role of the advanced nurse practitioner (ANP) is not regulated in the UK, which has led to wide variation in the skills, competencies and academic qualifications of nurses using this title. Urgent treatment centres (UTCs) require a broad and experienced knowledge base to meet the demand of patients presenting with undifferentiated illnesses and injuries, which can be stressful and challenging. To examine the perceptions and beliefs about ANP regulation, and to explore and discuss any ideas about proposed regulation. The author used interpretative phenomenological analysis to uncover valuable insights into the experiences of two ANPs working in an UTC, and their beliefs around regulation of the ANP role. Both ANPs had different backgrounds and qualifications yet still had similar perceptions and beliefs regarding the regulation of ANPs. Five main themes were developed from the interview transcripts. This study identified the need to consider the importance of ANPs' identity and the complex regulatory process required to standardise the role.

Factors Associated with Physician Tolerance of Uncertainty: an Observational Study.

BackgroundPhysicians need to learn and work amidst a plethora of uncertainties, which may drive burnout. Understanding differences in tolerance of uncertainty is an important research area.ObjectiveTo examine factors associated with tolerance of uncertainty, including well-being metrics such as burnout.DesignOnline confidential survey.SettingThe Massachusetts General Physicians Organization (MGPO).ParticipantsAll 2172 clinically active faculty in the MGPO.Main MeasuresWe examined associations for tolerance of uncertainty with demographic information, personal and professional characteristics, and physician well-being metrics.Key ResultsTwo thousand twenty (93%) physicians responded. Multivariable analyses identified significant associations of lower tolerance of uncertainty with female gender (OR, 1.23; 95% CI, 1.03–1.48); primary care practice (OR, 1.56; 95% CI, 1.22–2.00); years since training (OR, 0.99; 95% CI, 0.98–0.995); and lacking a trusted advisor (OR, 1.25; 95% CI, 1.03–1.53). Adjusting for demographic and professional characteristics, physicians with low tolerance of uncertainty had higher likelihood of being burned-out (OR, 3.06; 95% CI, 2.41–3.88), were less likely to be satisfied with career (OR, 0.37; 95% CI, 0.26–0.52), and less likely to be engaged at work (RR, 0.87; 95% CI, 0.84–0.90).ConclusionAt a time when concern about physician well-being is high, with much speculation about causes of burnout, we found a strong relationship between tolerance of uncertainty and physician well-being, across specialties. Particular attention likely needs to be paid to those with less experience, those in specialties with high rates of undifferentiated illness and uncertainty, such as primary care, and ensuring all physicians have access to a trusted advisor. These results generate the potential hypothesis that efforts focused in understanding and embracing uncertainty could be potentially effective for reducing burnout. This concept should be tested in prospective trials.

Coronavirus disease 2019 and dengue: two case reports

BackgroundThe pandemic of this century has overwhelmed the healthcare systems of affected countries, and all resources have been diverted to coronavirus disease 2019. At the onset, coronavirus disease 2019 can present as any other acute febrile undifferentiated illness. In tropical regions, clinicians are increasingly challenged to differentiate these febrile illnesses without the use of diagnostics. With this pandemic, many of these tropical diseases are neglected and go underreported. Dengue is holoendemic in the Maldives, and dengue viruses circulate throughout the year. Reports about coinfections with dengue virus and severe acute respiratory syndrome coronavirus 2 are scarce, and the outcome and the dynamics of the disease may be altered in the presence of coinfection. We have described the clinical manifestation and serial laboratory profile, and highlighted the atypical findings uncommon in dengue infection.Case presentationCase 1 was a 39-year old Asian male, presented on day 6 of dengue infection with warning signs. Reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 that was done as per hospital protocol was found to be positive. Case 2 was a 38-year old Asian male, was admitted on day 5 of illness with symptoms of acute respiratory infection with positive reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2. Evaluation of progressive leukopenia and thrombocytopenia showed positive dengue serology.ConclusionClinicians must be conscientious when working on the differential diagnosis of possible tropical diseases in cases of coronavirus disease 2019, specifically, when patients develop hemoconcentration, thrombocytopenia, and transaminitis with elevated expression of aspartate higher than alanine transaminase, which is frequently observed in dengue infection. Caution must be taken during the administration of intravenous fluids when treating patients with coronavirus disease 2019 and dengue coinfection, as coronavirus disease 2019 patients are more prone to develop pulmonary edema. Timely diagnosis and appropriate management are essential to avoid the devastating complications of severe forms of dengue infection. It is important to repeat and reconfirm the dengue serology in coronavirus disease 2019 patients to avoid false positivity. Diligence and care must be taken not to neglect other endemic tropical diseases in the region during the present pandemic.

Real-time patients’ perspectives about participating in teaching consultations in primary care: A questionnaire study

Introduction Patients presenting with undifferentiated illnesses provide valuable learning opportunities for medical students. Evidence detailing the factors that affect patient participation in undergraduate medical education is limited. This study examines how patients regard their participation in teaching consultations in primary care. Methods We conducted a cross-sectional questionnaire survey in four GP practices. We tested the relationship between variables of interest and willingness to participate, using hierarchical logistic regression. Results We analysed 525 questionnaires. 88% of respondents were willing to have students take part in their consultation, and 72% were willing to see a student alone before seeing the doctor. Older patients and those with less sensitive clinical problems were more likely to participate. Willingness to participate was also associated with patients’ perceptions of certain costs and benefits of participation. Respondents had poor knowledge about medical education, and a sizeable minority perceived a lack of autonomy about the presence of students in their encounters. More than one-third of respondents expressed the presence of a clinician as a precondition for approval of students’ performing some active roles. Discussion The findings have identified potential interventions to enhance patient involvement including patient education, respecting patient autonomy, and ensuring appropriate student supervision.

Emergency and primary care collaboration during COVID-19 pandemic: A quick systematic review of reviews.

COVID-19 is one of the deadliest viral infections to have hit the planet. There is urgent need to bridge the gaps in handling this pandemic by methodically synthesising available literature through a unique holistic perspective. A systematic review of articles regarding emergency and primary care during COVID-19 pandemic was carried out. PubMed, Scopus, Science Direct, Web of Science, and Google Scholar were screened for articles and qualitative data across various studies were coded and thematically analyzed. Narrative synthesis was achieved by themes identified from findings of studies. Out of n = 953 articles retrieved, we identified and critically appraised n = 7 articles of which n = 5 were narrative reviews, one was systematic review and one was scoping review from researchers across ten countries. Nine overlapping themes were identified under three broad domains – clinical understanding of the disease, social aspects of the disease, and its contextual implications during pandemic. This narrative synthesis draws up a holistic picture of recent reviews on clinical and social understanding of COVID-19 as a disease and as a pandemic. The overlap among nine themes identified in this review could mean that primary care-level screening, triaging, referral, and emergency care of COVID-19 patients in the backdrop of current clinical understanding of the pandemic are all intertwined. Coping with COVID-19 co-habitation and managing undifferentiated illnesses require a syndromic approach and deft handling at grass root levels. Inclusive health policy empowering inherent holistic specialties like family medicine and emergency medicine could be the prudent way forward during this pandemic.

Long-term outcomes of urinary tract infection (UTI) in Childhood (LUCI): protocol for an electronic record-linked cohort study

IntroductionCurrent guidelines advise the prompt diagnosis and treatment of urinary tract infection (UTI) in children to improve both short and longer term outcomes. However, the risk of long-term complications following...

Primary care chaplaincy: an intervention for complex presentation

To determine the responsiveness of primary care chaplaincy (PCC) to the current variety of presenting symptoms seen in primary care. This was done with a focus on complex and undifferentiated illness. Current presentations to primary care are often complex, undifferentiated and display risk factors for social isolation and loneliness. These are frequently associated with loss of well-being and spiritual issues. PCC provides holistic care for such patients but its efficacy is unknown in presentations representative of such issues. There is therefore a need to assess the characteristics of those attending PCC. The effectiveness of PCC relative to the type and number of presenting symptoms should also be analysed whilst evaluating impact on GP workload. This was a retrospective observational study based on routinely collected data. In total, 164 patients attended PCC; 75 were co-prescribed antidepressants (AD) and 89 were not (No-AD). Pre- and post-PCC well-being was assessed by the Warwick-Edinburgh mental well-being score. Presenting issue(s) data were collected on a separate questionnaire. GP appointment utilisation was measured for three months pre- and post-PCC. Those displaying undifferentiated illness and risk factors for social isolation and loneliness accessed PCC. PCC (No-AD) was associated with a clinically meaningful and statistically significant improvement in well-being in all presenting issues. This effect was maintained in those with multiple presenting issues. PCC was associated with a reduction in GP appointment utilisation in those not co-prescribed AD.

A novel immune biomarker IFI27 discriminates between influenza and bacteria in patients with suspected respiratory infection.

Host response biomarkers can accurately distinguish between influenza and bacterial infection. However, published biomarkers require the measurement of many genes, thereby making it difficult to implement them in clinical practice. This study aims to identify a single-gene biomarker with a high diagnostic accuracy equivalent to multi-gene biomarkers.In this study, we combined an integrated genomic analysis of 1071 individuals with in vitro experiments using well-established infection models.We identified a single-gene biomarker, IFI27, which had a high prediction accuracy (91%) equivalent to that obtained by multi-gene biomarkers. In vitro studies showed that IFI27 was upregulated by TLR7 in plasmacytoid dendritic cells, antigen-presenting cells that responded to influenza virus rather than bacteria. In vivo studies confirmed that IFI27 was expressed in influenza patients but not in bacterial infection, as demonstrated in multiple patient cohorts (n=521). In a large prospective study (n=439) of patients presented with undifferentiated respiratory illness (aetiologies included viral, bacterial and non-infectious conditions), IFI27 displayed 88% diagnostic accuracy (AUC) and 90% specificity in discriminating between influenza and bacterial infections.IFI27 represents a significant step forward in overcoming a translational barrier in applying genomic assay in clinical setting; its implementation may improve the diagnosis and management of respiratory infection.

The Roundhouse: an alternative model for primary care.

The challenges facing health care are well known. They include an ageing population, increasing expectations, and shrinking budgets.1 GPs remain key in the provision of primary care in the current model and report that they are failing to cope with rising demand.1 Increasing concern that the 10-minute GP appointment is obsolete2 in the face of increasing comorbidity adds to these pressures. NHS England’s Five Year Forward View nevertheless emphasises that ‘The foundation of NHS care will remain list-based primary care.’ 3 It also reiterates the concept of redeploying care from secondary to primary, so-called ‘shift left’. This article presents an alternative model for delivering GP services. No single element of the model is new but the overall concept is revolutionary. The model’s integrity is key. It seeks to improve productivity through using the skills and knowledge of the GP to maximum effect while introducing a range of healthcare professionals to relieve the pressure of less complex care. The daily tasks of a modern GP would be instantly recognisable to their predecessor at the inception of the NHS in 1948. They are booked for most of the working day for face-to-face consultations with patients who ‘believe themselves to be ill’. What is different is the GP’s training and remuneration. In 1948 a GP’s training would have comprised 6 years. The modern GP has up to 11 years of training. Despite this, modern GPs continue to see ‘undifferentiated illness’. In addition, most personally type up patient notes (probably 2 hours of a GP’s day is spent typing [D Lewis, unpublished data, 2014]), and address all clinical decision making (100–200 laboratory results, 150– 200 prescribing queries, 50–100 incoming hospital letters, per GP per day.) The modern GP is relatively more highly paid than their 1948 counterpart. …

Identification of Novel Zoonotic Activity of Bartonella spp., France.

Certain Bartonella species are known to cause afebrile bacteremia in humans and other mammals, including B. quintana, the agent of trench fever, and B. henselae, the agent of cat scratch disease. Reports have indicated that animal-associated Bartonella species may cause paucisymptomatic bacteremia and endocarditis in humans. We identified potentially zoonotic strains from 6 Bartonella species in samples from patients who had chronic, subjective symptoms and who reported tick bites. Three strains were B. henselae and 3 were from other animal-associated Bartonella spp. (B. doshiae, B. schoenbuchensis, and B. tribocorum). Genomic analysis of the isolated strains revealed differences from previously sequenced Bartonella strains. Our investigation identifed 3 novel Bartonella spp. strains with human pathogenic potential and showed that Bartonella spp. may be the cause of undifferentiated chronic illness in humans who have been bitten by ticks.

Identification of Novel Zoonotic Activity of Bartonella spp., France

Abstract Certain Bartonella species are known to cause afebrile bacteremia in humans and other mammals, including B. quintana, the agent of trench fever, and B. henselae, the agent of cat scratch disease. Reports have indicated that animal-associated Bartonella species may cause paucisymptomatic bacteremia and endocarditis in humans. We identified potentially zoonotic strains from 6 Bartonella species in samples from patients who had chronic, subjective symptoms and who reported tick bites. Three strains were B. henselae and 3 were from other animal-associated Bartonella spp. (B. doshiae, B. schoenbuchensis, and B. tribocorum). Genomic analysis of the isolated strains revealed differences from previously sequenced Bartonella strains. Our investigation identifed 3 novel Bartonella spp. strains with human pathogenic potential and showed that Bartonella spp. may be the cause of undifferentiated chronic illness in humans who have been bitten by ticks.