Testing Beats Lockdown, Hands Down
Volume 8, Issue 2 | June 14, 2023
In This Issue
Where we are in sepsis diagnosis
WHO boosts global pathogen surveillance coordination
Can diagnostics break the panic <—> neglect cycle?
New and Noteworthy
Where we are in sepsis diagnosis (Hint: It’s still not that great)
You’re pretty sure your patient’s blood is infected with bacteria. But you don’t know what the pathogen is, and you need to get the patient started on treatment ASAP. You want a test that will give you answers within an hour. That’s the challenge of septicemia, which was covered in a recent review in the Journal of Clinical Microbiology - and it’s an essentially impossible task today.
Sepsis is the poster child of complex, highly lethal bacterial infections. There are at least 1.7 million cases in the US per year, and 16% die even with current best treatment. Diagnosis is a bear: 40% of suspected sepsis cases are not an infection at all; blood cultures take two to three days; and even then 30 - 50% are false positives and 40-60% false negatives. As a result, physicians throw every treatment at the patient early, but this is costly and not without risk: Vancomycin (the antibiotic of last resort) damages the kidneys of 25% of patients.
Outside of blood culture, only one FDA-approved blood test for sepsis exists - all other tests have either been withdrawn or were never approved due to lack of predictive value. The test, known colloquially as T2B, detects six bacteria - but those only account for 50% of sepsis cases.
Commentary: Is nucleic-acid testing the future here? Almost certainly - PCR for known pathogens, NGS otherwise. But even these tests must overcome major challenges: In blood, cell-free DNA (cfDNA) from pathogens accounts for only 0.1 - 5.0% of the cfDNA in circulation, and most of that is fragmentary (i.e., neither capable of starting an infection nor evidence of a current infection); and some of the worst cases of sepsis have the lowest detectable pathogen levels.
International coordination for global pathogen surveillance post-COVID
In a previous issue we covered the challenges at GISAID - a genome repository originally created for influenza, which became a global go-to COVID resource. In an effort to maintain global pathogen surveillance, the WHO has announced a new platform called the International Pathogen Surveillance Network (IPSN). It’s not a sequence depository like GISAID, but instead is focused on best-practice sharing and coordination across nations. It joins other continuing genomic surveillance and data-analysis efforts, including the COVID-19 data portal (the front door of the European COVID-19 Data Platform), the BeYond COVID project, and the CRG Viral Beacon.
It’s official: Testing beats lockdown in every way
A recent Nature Scientific Report uses real-life COVID parameters to evaluate the financial and mortality consequences of a test-and-isolate strategy versus an optimized but indiscriminate community-lockdown strategy. The do-nothing scenario would have resulted in 2.95 million US deaths, versus the actual 1.1 million, so clearly what the nation did was better than doing nothing. But the important take-away is that test-and-isolate alone is 1) far better than lockdown alone and 2) just as good as doing both - and avoids all the economic, social, and cultural meltdown that lockdown creates.
Of course, at the beginning of the pandemic we did not have adequate tests, so community lockdown was an essential first step. However, the faster effective tests are available, the better the outcomes are.
Commentary: This is “only” a model, but it is clear that rapid development and deployment of effective tests must be the number-one priority in any infectious pandemic - which means that funding to maintain quick-start ability has to be the cornerstone of public health preparedness. This is very doable - PCR tests can be widely available in days after a pathogen has been sequenced. Tailored antigen tests can follow within weeks. It is both straightforward and cheap to be ready for the inevitable next pandemic.
Food for Thought
Can we abandon panic and neglect for preparedness - in diagnostics, at least?
Dr. Katelyn Jetelina’s (Your Local Epidemiologist) blog post today highlighted the Sisyphean nature of US public health; its title, Panic and neglect; panic and neglect, is a succinct overview of the state of affairs. She and other folks involved in pandemic response had hoped the COVID experience would change things - that we would learn the value of preparation and readiness.
Leaders from the Johns Hopkins Center for Health Security and the American of Clinical Lab Association (ACLA) are clearly on Dr. Jetelina’s team. At the end of 2022, they posted a proposal for a National Diagnostics Action Plan for the United States, recommending 10 priorities for pandemic preparation. It pointed out how fragmented and underfunded public health is in the US – five federal agencies (CDC, NIH, FDA, FEMA, ASPR) interacting with a heterogeneous mix of state, tribal, and local authorities, all with divergent and overlapping requirements and responsibilities. The recommendations included:
Setting up a national coordinating body for pre-crisis management;
Creating public/private contracts to fund both excess inventories and surge capacity (targeting a 30-day ramp up).
Commentary: The proposal’s fact-filled 11 pages show that the challenges are intimidating, and current resolve is inadequate to address them. We get it - there is not enough money in the federal or any state government to create brand-new infrastructure to address future threats. But let’s hope that governments and large employers are reading these and other recommendations. At the very least, we should be able to implement the steps that are relatively low-cost. Hopefully COVID showed us that just reacting to the pathogen is expensive in both lives and money.
Quick Hits
Correction: The links for this article are updated and now working correctly: The FDA has authorized the first blood test to predict the risk of severe pre-eclampsia. The life-threatening hypertensive disorder is one of the most common complications of pregnancy and the postpartum period, and disproportionately affects Black women.
A meta-analysis of 27 studies from 13 countries found that dogs can detect COVID with 81 - 97% sensitivity and 83 - 100% specificity. Woof!
Scientists have identified 49 genes that are associated with the development of severe disease due to COVID infection. The study, published in Nature, also identified drugs that could be of therapeutic benefit for patients with these genes.
The Marburg virus outbreaks in both Tanzania and Equatorial Guinea have ended, according to the WHO - Tanzania’s on June 2 and Equatorial Guinea’s on June 8. The outbreaks were the first of their kind in both nations.