10 August 2019
Field Notes III
Welcome back to Field Notes! This week we’re leaning in on the infectious disease front, covering drug resistance, vector control, and CRISPR diagnostics. Hope you enjoy!
Are the Mosquitoes In Charge?
According to Timothy C. Winegard’s new book “The Mosquito: A Human History of Our Deadliest Predator”, pretty much. Winegard describes how Mosquitoes and, their deadly pathogenic passengers, have played a role in determining virtually every major geopolitical event of the past millennium (the Romans seem to have gotten some of the best and worst of it). And who doesn’t love the occasional riff on Guns, Germs, and Steel-style theories of everything? While a recent review of the book in the New Yorker thinks Winegard gives a bit too much credit to our winged oppressors, it’s worth reading and contains a few mind-blowing morsels, including:
In total, Winegard estimates that mosquitoes have killed more people than any other single cause — fifty-two billion of us, nearly half of all humans who have ever lived. He calls them “our apex predator,” “the destroyer of worlds,” and “the ultimate agent of historical change.”
“Show me the incentives and I will show you the outcome” — Charlie Munger / the Antibiotic Market
There’s perhaps no better example of a market failure than the lack of incentives for development of novel antibiotics. And now, despite the emerging threat of superbugs, market forces have driven biotech innovators to abandon the search for new drugs to treat these deadly infections. In overly simplistic terms, successful development of a novel antibiotic does not carry the same financial reward for companies and investors as many other classes of drugs, thus making it difficult to justify the cost of developing these life-saving therapies. So, while we still have a long way to go in terms of realigning incentives to drive innovation in this area, the U.S. Government took as step in the right direction last week by introducing new guidance around how these drugs are paid for by Medicare. The new rule will essentially give hospitals greater financial flexibility to prescribe and use novel antibiotics developed to treat drug-resistant infections. There’s so much to talk about here that we’ll just point you to this helpful summary and invite you to reach out to us directly if you have questions!
Let Me CRISPR That For You
The hype around CRISPR as an approach to genome editing has been well covered (and rightfully so — it’s cool!) and the first CRISPR-based therapies are starting to make their way into the clinic. But less attention has been paid to CRISPR-based diagnostics, which companies like Mammoth Biosciences (out of Berkley) and Sherlock Biosciences (out of the Broad Institute) are developing for diseases ranging from cancers to mosquito-borne pathogens like Zike and Dengue. The approach is highly intuitive: use the honing function of RNA-guided CRISPR systems (used to target nucleic acid sequences for erasure or replacement in CRISPER-based therapies) to identify nucleic acid sequences from target pathogens. Pair this honing ability with the release of “reporter molecules” that can be detected with existing tools and you have a low-cost, highly sensitive diagnostic approach. I recommend this helpful overview of CRISPR diagnostics in Nature that discusses some of the technical approaches and business model dynamics of the space.
Alarming Surge in Drug-Resistant HIV Uncovered
We talk a lot about antibacterial resistance, but emerging resistance to commonly used antivirals, or drugs used to control disease in people living with deadly viruses such as HIV, has now also reached a tipping point. Surveys by the WHO recently found that 12 countries in Africa, Asia and the Americas have now surpassed acceptable levels of drug resistance against two drugs that constitute the backbone of HIV treatment: efavirenz and nevirapine. More than 10% of adults with the virus have now developed resistance to these drugs, and the WHO now recommends that countries use dolutegravir, which is not only more tolerable, but is also thought o carry a lower risk of emerging resistance. Notably, major stakeholders within the global health community collaborated in 2017 to lower the price of dolutegravir and increase access to patients in low- and middle-income countries.
The Antimalarials Are Not Alright
The battle against mosquito-borne pathogens is becoming a race to combat resistance for tried and true therapies like artemisinin class drugs, which have been used for decades (and possibly centuries) to treat the disease. This alarming article from CIDRAP details how widespread drug-resistant mosquitoes have become in parts of Asia:
One of the studies found that the KEL1/PLA1 strain of Plasmodium falciparum, the parasite that causes malaria, now accounts for more than 80% of the malaria parasites in northeastern Thailand and Vietnam, and has acquired new genetic mutations that have enhanced its fitness and ability to resist treatment.
A small trial called Tracking Resistance to Artemisinin Collaboration (TRACII) found that the impact of these mutations is leading to alarming levels of resistance:
Among the 140 patients treated with dihydroartemisinin-piperaquine from September 2015 through January 2018, the overall efficacy at day 42 was 50%, with treatment failure rates of 87.3% in northeastern Thailand, 61.8% in western Cambodia, 52.9% in southwestern Vietnam, and 26.6% in northeastern Cambodia.
These troubling data underscore the importance of investing in improved diagnostics and drugs, and ultimately vaccines, for one of the leading killers globally.
That’s it for this week!
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