Discrepant serological findings in SARS-CoV-2 PCR-negative hospitalized patients with fever and acute respiratory symptoms during the pandemic.

Coronavirus Disease 2019 (COVID-19) serology has an evolving role in the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, its use in hospitalized patients with acute respiratory symptoms remains unclear. Hospitalized patients with acute respiratory illness admitted to an isolation ward were recruited. All patients had negative nasopharyngeal swab polymerase chain reaction (PCR) for SARS-CoV-2. Serological studies using four separate assays (cPass: surrogate neutralizing enzyme-linked immunosorbent assay [ELISA]; Elecsys: N-antigen based chemiluminescent assay; SFB: S protein flow-based; epitope peptide-based ELISA) were performed on stored plasma collected from patients during the initial hospital stay, and a convalescent visit 4-12 weeks later. Of the 51 patients studied (aged 54, interquartile range 21-84; 62.7% male), no patients tested positive on the Elecsys or cPass assays. Out of 51 patients, 5 had antibodies detected on B-cell Epitope Assay and 3/51 had antibodies detected on SFB assay. These 8 patients with positive serological test to COVID-19 were more likely to have a high-risk occupation (p = 0.039), bacterial infection (p = 0.028), and neutrophilia (p = 0.013) during their initial hospital admission. Discrepant COVID-19 serological findings were observed among those with recent hospital admissions and bacterial infections. The positive serological findings within our cohort raise important questions about the interpretation of sero-epidemiology during the current pandemic.

Influenza A(H3N2) Outbreak on a University Campus - Michigan, October-November 2021.

On November 10, 2021, the Michigan Department of Health and Human Services (MDHHS) was notified of a rapid increase in influenza A(H3N2) cases by the University Health Service (UHS) at the University of Michigan in Ann Arbor. Because this outbreak represented some of the first substantial influenza activity during the COVID-19 pandemic, CDC, in collaboration with the university, MDHHS, and local partners conducted an investigation to characterize and help control the outbreak. Beginning August 1, 2021, persons with COVID-19-like* or influenza-like illness evaluated at UHS received testing for SARS-CoV-2, influenza, and respiratory syncytial viruses by rapid multiplex molecular assay.† During October 6-November 19, a total of 745 laboratory-confirmed influenza cases were identified.§ Demographic information, genetic characterization of viruses, and influenza vaccination history data were reviewed. This activity was conducted consistent with applicable federal law and CDC policy.¶.

Low uptake of isoniazid window prophylaxis in patients exposed to a health-care worker with pulmonary tuberculosis in a paediatric ward.

AIM: A nurse on a paediatric multidisciplinary ward was diagnosed with smear-positive pulmonary tuberculosis. Children <2 years old, immunocompromised, or >40 h of contact (n = 173) were contact-traced. METHODS: Children received clinical review, chest X-ray, tuberculin skin test (TST; <5 years old) and/or an interferon-gamma release assay (Quantiferon TB-Gold, ≥5 years old). Infants <6 months old or children <5 years old screened <2 months from exposure were recommended isoniazid window prophylaxis (WP) until a repeat TST at 6 months old or 8-10 weeks after the last exposure to the index case, respectively. Empiric treatment for latent tuberculosis infection (LTBI) was individually considered for immunocompromised patients. RESULTS: Of 173 children (135 immunocompetent, 38 immunocompromised), two were uncontactable, seven refused screening and two immunocompromised children excluded. Eight of 126 immunocompetent children were diagnosed with LTBI (initial TST positive n = 7, TST conversion n = 1); seven started isoniazid. Thirty-two of 36 immunocompetent children were recommended WP; 15 accepted (one non-compliant after 1 month). Six of seven immunocompromised children accepted empiric LTBI treatment due to severe immunosuppression/initial indeterminate Quantiferon TB-Gold result. Of 15 immunocompromised children offered WP, only five accepted. CONCLUSIONS: There was high acceptance of screening but low uptake of isoniazid WP in high-risk children exposed to pulmonary tuberculosis. Perception of exposure risk and chemoprophylaxis should be explored further.

SARS-CoV-2 in migrant worker dormitories: Geospatial epidemiology supporting outbreak management.

BACKGROUND: Migrant worker dormitories-residential complexes where 10-24 workers share living spaces-account for the majority of cases of SARS-CoV-2 infection in Singapore. To prevent overspill of transmission to the wider population, starting in early April 2020, residents were confined to their dormitories while measures were put in place to arrest the spread of infection. This descriptive study presents epidemiological data for a population of more than 60 000 migrant workers living in two barracks-style and four apartment-style dormitories located in western Singapore from April 3 to June 10, 2020. METHODS: Our report draws from data obtained over the first 50 days of outbreak management in order to describe SARS-CoV-2 transmission in high-density housing environments. Cumulative counts of SARS-CoV-2 cases and numbers of housing units affected were analyzed to report the harmonic means of harmonic means of doubling times and their 95% confidence intervals (CI). RESULTS: Multiple transmission peaks were identified involving at least 5467 cases of SARS-CoV-2 infection across six dormitories. Our geospatial heat maps gave an early indication of outbreak severity in affected buildings. We found that the number of cases of SARS-CoV-2 infection doubled every 1.56 days (95% CI 1.29-1.96) in barracks-style buildings. The corresponding doubling time for apartment-style buildings was 2.65 days (95% CI 2.01-3.87). CONCLUSIONS: Geospatial epidemiology was useful in shaping outbreak management strategies in dormitories. Our results indicate that building design plays an integral role in transmission and should be considered in the prevention of future outbreaks.

Establishing a New Normal for Hospital Care: A Whole of Hospital Approach to Coronavirus Disease 2019 (COVID-19).

Singapore's hospitals had prepared to receive patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), planning various scenarios and levels of surge with a policy of isolating all confirmed cases as inpatients. The National University Hospital adopted a whole of hospital approach to coronavirus disease 2019 (COVID-19) with 3 primary goals: zero hospital-acquired COVID-19, all patients receive timely necessary care, and maintenance of staff morale. These goals to date have been met. A large influx of COVID-19 cases required significant transformation of clinical and operational processes. Isolation room numbers almost tripled and dedicated COVID-19 cohort wards were established, elective care was postponed, and intensive care units were augmented with equipment and manpower. In the wake of the surge, establishing a new normal for hospital care requires maintaining vigilance to detect endemic COVID-19, establishing contingency plans to ramp up in case of another surge, while returning to business as usual.

Scenarios to Manage the Demand for N95 Respirators for Healthcare Workers During the COVID-19 Pandemic.

BACKGROUND: By estimating N95 respirator demand based on simulated epidemics, we aim to assist planning efforts requiring estimations of respirator demand for the healthcare system to continue operating safely in the coming months. METHODS: We assess respiratory needs over the course of mild, moderate and severe epidemic scenarios within Singapore as a case study using a transmission dynamic model. The number of respirators required within the respiratory isolation wards and intensive care units was estimated over the course of the epidemic. We also considered single-use, extended-use and prolonged-use strategies for N95 respirators for use by healthcare workers treating suspected but negative (misclassified) or confirmed COVID-19 patients. RESULTS: Depending on the confirmed to misclassified case ratio, from 1:0 to 1:10, a range of 117.1 million to 1.1 billion masks are required for single-use. This decreases to 71.6-784.4 million for extended-use and 12.8-148.2 million for prolonged-use, representing a 31.8-38.9% and 86.5-89.1% reduction, respectively. CONCLUSION: An extended-use policy should be considered when short-term supply chains are strained but planning measures are in place to ensure long-term availability. With severe shortage expectations from a severe epidemic, as some European countries have experienced, prolonged use is necessary to prolong supply.

Responding to the COVID-19 pandemic: The role of occupational health services in a tertiary hospital in Singapore.

With coronavirus disease 2019 declared a Public Health Emergency of International Concern on 30 January 2020, occupational health services in a tertiary hospital in Singapore stepped up via a three-pronged approach, namely, protection of individual staff, protection of staff workforce, and prevention of nosocomial spread so as to support business continuity plans. Despite the multiple new challenges brought by the COVID-19 pandemic, the hospital's occupational health services were able to adapt and keep all employees and patients safe with strong support from senior management and close collaboration with various departments.

Responding to COVID-19: how an academic infectious diseases division mobilized in Singapore.

BACKGROUND: On January 30, COVID-19 was declared a Public Health Emergency of International Concern-a week after Singapore's first imported case and 5 days before local transmission. The National University Hospital (NUH) is Singapore's third largest hospital with 1200 beds, heavy clinical workloads, and major roles in research and teaching. MAIN BODY: With memories of SARS still vivid, there was an urgent requirement for the NUH Division of Infectious Diseases to adapt-undergoing major reorganization to face rapidly changing priorities while ensuring usual essential services and standards. Leveraging on individual strengths, our division mobilized to meet the demands of COVID-19 while engaging in high-level coordination, strategy, and advocacy. We present our experience of the 60 days since the nation's first case. During this time, our hospital has managed 3030 suspect cases, including 1300 inpatients, 37 confirmed cases, and overseen 4384 samples tested for COVID-19. CONCLUSION: Complex hospital adaptations were supported by an unprecedented number of workflows and coordination channels essential to safe and effective operations. The actions we describe, aligned with international recommendations and emerging evidence-based best practices, may serve as a framework for other divisions and institutions facing the spread of COVID-19 globally.

A Prediction Tool for the Presence of Ceftriaxone-Resistant Uropathogens upon Hospital Admission.

Antimicrobial resistance among uropathogens is a particularly pressing problem in the Asia-Pacific region. The objectives of this study were to determine the incidence and susceptibility of uropathogens upon hospital admission and to develop a risk-scoring model to predict the presence of ceftriaxone-resistance uropathogens (CrP). This was a retrospective observational cohort study of patients with a positive urine culture within 48 h of presentation at National University Hospital, Singapore between June 2015 and August 2015. Escherichia coli was the most common uropathogen isolated (51.7%), followed by Klebsiella pneumonia (15.1%) and Pseudomonas aeruginosa (8.2%). Overall, 372 out of 869 isolates (42.8%) were resistant to ceftriaxone. Hospitalization for ≥2 days within past 30 days, antibiotic use within the past 3 months and male gender were associated with the presence of CrP. A risk score based on these parameters successfully predicted CrP with an area under the curve of 0.68. The risk score will help clinicians to accurately predict antibiotic resistance at the individual patient level and allow physicians to safely prescribe empiric ceftriaxone in patients at low risk of CrP, thus reducing the antibiotic selection pressure that is driving carbapenem resistance in hospitals throughout Asia.

Selective reporting of fluoroquinolone susceptibility as a stewardship measure is of marginal benefit.

A retrospective time series analysis was conducted to compare inpatient fluoroquinolone use when susceptibilities were masked and after susceptibilities were unmasked. Although inappropriate culture-directed prescriptions increased, overall fluoroquinolone usage decreased. Culture-directed therapy was a small part of fluoroquinolone usage; hence, efforts should target empiric use to reduce overall consumption.

A screening strategy for latent tuberculosis in healthcare workers: Cost-effectiveness and budget impact of universal versus targeted screening.

OBJECTIVE: To evaluate the clinical, cost-efficiency, and budgetary implications of universal versus targeted latent tuberculosis infection (LTBI) screening strategies among healthcare workers (HCWs) in an intermediate tuberculosis (TB)-burden country. DESIGN: Pragmatic cost-effectiveness and budget impact analysis using decision-analytic modeling. SETTING: A tertiary-care hospital in Singapore. METHODS: We compared 7 potentially implementable LTBI screening programs including universal and targeted strategies with different screening frequencies. Feasible targeting methods included stratification by country of origin (a proxy for risk of prior TB exposure) and by high-risk occupation. The clinical and financial consequences of each strategy were estimated relative to "no screening" (current practice) and compared to locally appropriate cost-effectiveness thresholds. All analyses were conducted from the hospital's perspective over a 3-year time horizon, based on the typical hospital planning period. Parameter uncertainties were accounted for using sensitivity analyses. RESULTS: In our model, relative to current practice, screening new international hires and triennial screening of existing high-risk workers is most cost-effective (US$58 per quality adjusted life year [QALY]) and decreases active TB cases from 19 to 14. Screening all new hires combined with triennial universal screening, with or without annual high-risk screening or annual universal screening, reduced active TB to a range of 19 to 6 cases, but these strategies are less cost-effective and require substantially higher expenditures. CONCLUSIONS: Targeted LTBI screening for HCWs can be highly cost-effective for hospitals in settings similar to Singapore. More inclusive screening strategies (including regular universal screening) can yield better outcomes but are less efficient and may even be unaffordable.

Distinguishing Zika and Dengue Viruses through Simple Clinical Assessment, Singapore.

Dengue virus and Zika virus coexist in tropical regions in Asia where healthcare resources are limited; differentiating the 2 viruses is challenging. We showed in a case-control discovery cohort, and replicated in a validation cohort, that the diagnostic indices of conjunctivitis, platelet count, and monocyte count reliably distinguished between these viruses.

Diagnosis and treatment of Clostridium difficile in adults: a systematic review.

IMPORTANCE: Since 2000, the incidence and severity of Clostridium difficile infection (CDI) have increased. OBJECTIVE: To review current evidence regarding best practices for the diagnosis and treatment of CDI in adults (age ≥ 18 years). EVIDENCE REVIEW: Ovid MEDLINE and Cochrane databases were searched using keywords relevant to the diagnosis and treatment of CDI in adults. Articles published between January 1978 and October 31, 2014, were selected for inclusion based on targeted keyword searches, manual review of bibliographies, and whether the article was a guideline, systematic review, or meta-analysis published within the past 10 years. Of 4682 articles initially identified, 196 were selected for full review. Of these, the most pertinent 116 articles were included. Clinical trials, large observational studies, and more recently published articles were prioritized in the selection process. FINDINGS: Laboratory testing cannot distinguish between asymptomatic colonization and symptomatic infection with C difficile. Diagnostic approaches are complex due to the availability of multiple testing strategies. Multistep algorithms using polymerase chain reaction (PCR) for the toxin gene(s) or single-step PCR on liquid stool samples have the best test performance characteristics (for multistep: sensitivity was 0.68-1.00 and specificity was 0.92-1.00; and for single step: sensitivity was 0.86-0.92 and specificity was 0.94-0.97). Vancomycin and metronidazole are first-line therapies for most patients, although treatment failures have been associated with metronidazole in severe or complicated cases of CDI. Recent data demonstrate clinical success rates of 66.3% for metronidazole vs 78.5% for vancomycin for severe CDI. Newer therapies show promising results, including fidaxomicin (similar clinical cure rates to vancomycin, with lower recurrence rates for fidaxomicin, 15.4% vs vancomycin, 25.3%; P = .005) and fecal microbiota transplantation (response rates of 83%-94% for recurrent CDI). CONCLUSIONS AND RELEVANCE: Diagnostic testing for CDI should be performed only in symptomatic patients. Treatment strategies should be based on disease severity, history of prior CDI, and the individual patient's risk of recurrence. Vancomycin is the treatment of choice for severe or complicated CDI, with or without adjunctive therapies. Metronidazole is appropriate for mild disease. Fidaxomicin is a therapeutic option for patients with recurrent CDI or a high risk of recurrence. Fecal microbiota transplantation is associated with symptom resolution of recurrent CDI but its role in primary and severe CDI is not established.

Infectious complications of dialysis access devices.

Infectious complications remain a major source of morbidity and mortality for patients with end-stage renal disease on dialysis. The majority of these complications are related to dialysis access devices, and as such represent a potentially modifiable risk factor. This article reviews the important infectious complications associated with dialysis access, including both hemodialysis and peritoneal dialysis. The discussion highlights the epidemiology, management, and prevention of dialysis access infections.

Seasonal influenza A (H1N1) infection in early pregnancy and second trimester fetal demise.

A second trimester fetal demise followed influenza-like illness in early pregnancy. Influenza A virus (H1N1) was identified in maternal and fetal tissue, confirming transplacental passage. These findings suggested a causal relationship between early exposure and fetal demise. Management of future influenza outbreaks should include evaluation of products of conception associated with fetal loss.