Correction: Two-test algorithms for infectious disease diagnosis: Implications for COVID-19.

[This corrects the article DOI: 10.1371/journal.pgph.0000293.].

SARS-CoV-2 diagnostic testing rates determine the sensitivity of genomic surveillance programs.

The first step in SARS-CoV-2 genomic surveillance is testing to identify people who are infected. However, global testing rates are falling as we emerge from the acute health emergency and remain low in many low- and middle-income countries (mean = 27 tests per 100,000 people per day). We simulated COVID-19 epidemics in a prototypical low- and middle-income country to investigate how testing rates, sampling strategies and sequencing proportions jointly impact surveillance outcomes, and showed that low testing rates and spatiotemporal biases delay time to detection of new variants by weeks to months and can lead to unreliable estimates of variant prevalence, even when the proportion of samples sequenced is increased. Accordingly, investments in wider access to diagnostics to support testing rates of approximately 100 tests per 100,000 people per day could enable more timely detection of new variants and reliable estimates of variant prevalence. The performance of global SARS-CoV-2 genomic surveillance programs is fundamentally limited by access to diagnostic testing.

Strategies for Using Antigen Rapid Diagnostic Tests to Reduce Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 in Low- and Middle-Income Countries: A Mathematical Modelling Study Applied to Zambia.

BACKGROUND: Increasing the availability of antigen rapid diagnostic tests (Ag-RDTs) in low- and middle-income countries (LMICs) is key to alleviating global SARS-CoV-2 testing inequity (median testing rate in December 2021-March 2022 when the Omicron variant was spreading in multiple countries: high-income countries = 600 tests/100 000 people/day; LMICs = 14 tests/100 000 people/day). However, target testing levels and effectiveness of asymptomatic community screening to impact SARS-CoV-2 transmission in LMICs are unclear. METHODS: We used Propelling Action for Testing and Treating (PATAT), an LMIC-focused agent-based model to simulate coronavirus disease 2019 (COVID-19) epidemics, varying the amount of Ag-RDTs available for symptomatic testing at healthcare facilities and asymptomatic community testing in different social settings. We assumed that testing was a function of access to healthcare facilities and availability of Ag-RDTs. We explicitly modelled symptomatic testing demand from individuals without SARS-CoV-2 and measured impact based on the number of infections averted due to test-and-isolate. RESULTS: Testing symptomatic individuals yields greater benefits than any asymptomatic community testing strategy until most symptomatic individuals who sought testing have been tested. Meeting symptomatic testing demand likely requires at least 200-400 tests/100 000 people/day, on average, as symptomatic testing demand is highly influenced by individuals without SARS-CoV-2. After symptomatic testing demand is satisfied, excess tests to proactively screen for asymptomatic infections among household members yield the largest additional infections averted. CONCLUSIONS: Testing strategies aimed at reducing transmission should prioritize symptomatic testing and incentivizing test-positive individuals to adhere to isolation to maximize effectiveness.

SARS-CoV-2 diagnostic testing rates determine the sensitivity of genomic surveillance programs.

The first step in SARS-CoV-2 genomic surveillance is testing to identify infected people. However, global testing rates are falling as we emerge from the acute health emergency and remain low in many low- and middle-income countries (LMICs) (mean = 27 tests/100,000 people/day). We simulated COVID-19 epidemics in a prototypical LMIC to investigate how testing rates, sampling strategies, and sequencing proportions jointly impact surveillance outcomes and showed that low testing rates and spatiotemporal biases delay time-to-detection of new variants by weeks-to-months and can lead to unreliable estimates of variant prevalence even when the proportion of samples sequenced is increased. Accordingly, investments in wider access to diagnostics to support testing rates of ~100 tests/100,000 people/day could enable more timely detection of new variants and reliable estimates of variant prevalence. The performance of global SARS-CoV-2 genomic surveillance programs is fundamentally limited by access to diagnostic testing.

Optimal use of COVID-19 Ag-RDT screening at border crossings to prevent community transmission: A modeling analysis.

Countries around the world have implemented restrictions on mobility, especially cross-border travel to reduce or prevent SARS-CoV-2 community transmission. Rapid antigen testing (Ag-RDT), with on-site administration and rapid turnaround time may provide a valuable screening measure to ease cross-border travel while minimizing risk of local transmission. To maximize impact, we developed an optimal Ag-RDT screening algorithm for cross-border entry. Using a previously developed mathematical model, we determined the daily number of imported COVID-19 cases that would generate no more than a relative 1% increase in cases over one month for different effective reproductive numbers (Rt) and COVID-19 prevalence within the recipient country. We then developed an algorithm-for differing levels of Rt, arrivals per day, mode of travel, and SARS-CoV-2 prevalence amongst travelers-to determine the minimum proportion of people that would need Ag-RDT testing at border crossings to ensure no greater than the relative 1% community spread increase. When daily international arrivals and/or COVID-19 prevalence amongst arrivals increases, the proportion of arrivals required to test using Ag-RDT increases. At very high numbers of international arrivals/COVID-19 prevalence, Ag-RDT testing is not sufficient to prevent increased community spread, especially when recipient country prevalence and Rt are low. In these cases, Ag-RDT screening would need to be supplemented with other measures to prevent an increase in community transmission. An efficient Ag-RDT algorithm for SARS-CoV-2 testing depends strongly on the epidemic status within the recipient country, volume of travel, proportion of land and air arrivals, test sensitivity, and COVID-19 prevalence among travelers.

Two-test algorithms for infectious disease diagnosis: Implications for COVID-19.

Diagnostic assays for various infectious diseases, including COVID-19, have been challenged for their utility as standalone point-of-care diagnostic tests due to suboptimal accuracy, complexity, high cost or long turnaround times for results. It is therefore critical to optimise their use to meet the needs of users. We used a simulation approach to estimate diagnostic outcomes, number of tests required and average turnaround time of using two-test algorithms compared with singular testing; the two tests were reverse transcription polymerase chain reaction (RT-PCR) and an antigen-based rapid diagnostic test (Ag-RDT). A web-based application of the model was developed to visualise and compare diagnostic outcomes for different disease prevalence and test performance characteristics (sensitivity and specificity). We tested the model using hypothetical prevalence data for COVID-19, representing low- and high-prevalence contexts and performance characteristics of RT-PCR and Ag-RDTs. The two-test algorithm when RT-PCR was applied to samples negative by Ag-RDT predicted gains in sensitivity of 27% and 7%, respectively, compared with Ag-RDT and RT-PCR alone. Similarly, when RT-PCR was applied to samples positive by Ag-RDT, specificity gains of 2.9% and 1.9%, respectively, were predicted. The algorithm using Ag-RDT followed by RT-PCR as a confirmatory test for positive patients limited the requirement of RT-PCR testing resources to 16,400 and 3,034 tests when testing a population of 100,000 with an infection prevalence of 20% and 0.05%, respectively. A two-test algorithm comprising a rapid screening test followed by confirmatory laboratory testing can reduce false positive rate, produce rapid results and conserve laboratory resources, but can lead to large number of missed cases in high prevalence setting. The web application of the model can identify the best testing strategies, tailored to specific use cases and we also present some examples how it was used as part of the Access to Covid-19 Tools (ACT) Accelerator Diagnostics Pillar.

Sonographic Evaluation and Monitoring of Pneumoperitoneum After Air Enema Reduction for Intussusception.

Abdominal radiography and computed tomography scans are standard tests to diagnose pneumoperitoneum. With the growing availability of point-of-care ultrasound, pneumoperitoneum may be diagnosed in settings without easy access to radiography or computed tomography, such as in overcrowded emergency departments or resource-poor environments. The use of point-of-care ultrasound to diagnose or monitor pneumoperitoneum has been described in adult but not pediatric patients. We present a case of point-of-care ultrasound detection of pneumoperitoneum and monitoring for tension pneumoperitoneum, after failed air enema reduction for intussusception in an infant.

Burden of disease, health indicators and challenges for epidemiology in North America.

BACKGROUND: Commissioned by the International Epidemiological Association, this article is part of a series on burden of disease, health indicators and the challenges faced by epidemiologists in bringing their discoveries to provide equitable benefit to the populations in their regions and globally. This report covers the health status and epidemiological capacity in the North American region (USA and Canada). METHODS: We assessed data from country-specific sources to identify health priorities and areas of greatest need for modifiable risk factors. We examined inequalities in health as a function of social deprivation. We also reviewed information on epidemiological capacity building and scientific contributions by epidemiologists in the region. FINDINGS: The USA and Canada enjoy technologically advanced healthcare systems that, in principle, prioritize preventive services. Both countries experience a life expectancy at birth that is higher than the global mean. Health indicator measures are consistently worse in the USA than in Canada for many outcomes, although typically by only marginal amounts. Socio-economic and racial/ethnic disparities in indicators exist for many diseases and risk factors in the USA. To a lesser extent, these social inequalities also exist in Canada, particularly among the Aboriginal populations. Epidemiology is a well-established discipline in the region, with many degree-granting schools, societies and job opportunities in the public and private sectors. North American epidemiologists have made important contributions in disease control and prevention and provide nearly a third of the global scientific output via published papers. CONCLUSIONS: Critical challenges for North American epidemiologists include social determinants of disease distribution and the underlying inequalities in access to and benefit from preventive services and healthcare, particularly in the USA. The gains in life expectancy also underscore the need for research on health promotion and prevention of disease and disability in older adults. The diversity in epidemiological subspecialties poses new challenges in training and accreditation and has occurred in parallel with a decrease in research funding.

Stent-assisted coiling of wide-necked aneurysms in the setting of acute subarachnoid hemorrhage: experience in 65 patients.

BACKGROUND: Stent-assisted coiling in the setting of subarachnoid hemorrhage remains controversial. Currently, there is a paucity of data regarding the utility of this procedure and the risks of hemorrhagic and ischemic complications. OBJECTIVE: To assess the utility of stent-assisted coil embolization and pretreatment with antiplatelet agents in the management of ruptured wide-necked aneurysms. METHODS: A retrospective study of 65 patients with ruptured wide-necked aneurysms treated with stent-assisted coiling. Patients with hydrocephalus or a Hunt and Hess grade ≥ III received a ventriculostomy before endovascular intervention. Patients were treated intraoperatively with 600 mg of clopidogrel and maintained on daily doses of 75 mg of clopidogrel and 81 mg of aspirin. The Glasgow outcome scale (GOS) score was recorded at the time of discharge. We identified major bleeding complications secondary to antiplatelet therapy and cases of in-stent thrombosis that required periprocedural thrombolysis. RESULTS: Of the aneurysms, 66.2% arose within the anterior circulation; 69.2% of patients presented with hydrocephalus or a Hunt and Hess grade ≥ III and required a ventriculostomy. A good outcome (GOS of 4 or 5) was achieved in 63.1% of patients, and the overall mortality rate was 16.9%. There were 10 (15.38%) major complications associated with bleeding secondary to antiplatelet therapy (5 patients, 7.7%) or intraoperative in-stent thrombosis (5 patients, 7.7%). Three (4.6%) patients had a fatal hemorrhage. CONCLUSION: Our findings suggest that stent-assisted coiling and routine treatment with antiplatelet agents is a viable option in the management of ruptured wide-necked aneurysms.