CETH Projects and Publications

Snakebite is arguably the most neglected of neglected tropical diseases. It is a disease of poverty with numbers of fatalities comparable to that of AIDS in some developing countries. Predominantly killing young and otherwise healthy individuals, neurotoxins paralyze their victims, resulting in death by respiratory failure. Most of these victims would likely survive with early access to emergency care. There is currently little funding to devise new approaches to address this problem, but Drs. Lewin and Samuel are now grantees of the Wellcome Trust and have made inroads to solving a part of this ancient scourge and persistent modern tragedy.

In collaboration with UCSF, we recently made the first successful attempt to create a human model for neurotoxic paralysis specifically designed to test whether anticholinesterases can reverse paralysis caused by a drug that mimics neurotoxic snakebite paralysis. Our findings suggested a novel strategy for field treatment that could substantially decrease the worldwide burden of neurotoxic envenomation. Subsequently, Dr. Lewin discovered that varespladib, a small molecule inhibitor of the lethal sPLA2, could block the most commonly lethal component of snake venom from the majority of the world’s most venomous snakes. Clinical trials of that drug are slated to start in late 2021 in the US and India.

Snakebite

Chowdhury A, Zdenek CN, Lewin MR, Carter R, Jagar t, Ostanek E, Harjen H, Aldridge M, Soria R, Haw G, Fry BG.
Venom-Induced Blood Disturbances by Palearctic Viperid Snakes, and Their Relative Neutralization by Antivenoms and Enzyme-Inhibitors.
Front. Immunol. 2021 Jun; 12:688802. doi: 10.3389/fimmu.2021.688802

Salvador GHM, Borges RJ, Lomonte B, Lewin MR, Fontes MRM.
The synthetic varespladib molecule is a multi-functional inhibitor for PLA2 and PLA2-like ophidic toxins.
Biochim Biophys Acta. 2021 Jul;1865(7):129913. doi: 10.1016/j.bbagen.2021.129913. Epub 2021 Apr 16. PMID: 33865953.

Fontana Oliveira IC, Gutiérrez JM, Lewin MR, Oshima-Franco Y.
Varespladib (LY315920) inhibits neuromuscular blockade induced by Oxyuranus scutellatus venom in a nerve-muscle preparation.
Toxicon. 2020 Nov;187:101-104. doi: 10.1016/j.toxicon.2020.08.023. PMID: 32889027.

Gutiérrez JM, Lewin MR, Williams DJ, Lomonte B. Varespladib (LY315920) and Methyl Varespladib (LY333013) Abrogate or Delay Lethality Induced by Presynaptically Acting Neurotoxic Snake Venoms. Toxins (Basel). 2020 Feb 20;12(2):131. doi: 10.3390/toxins12020131. PMID: 32093386; PMCID: PMC7076770.

Salvador GHM, Gomes AAS, Bryan-Quirós W, Fernández J, Lewin MR, Gutiérrez JM, Lomonte B, Fontes MRM.
Structural basis for phospholipase A2-like toxin inhibition by the synthetic compound Varespladib (LY315920).
Sci Rep. 2019 Nov 20;9(1):17203. doi: 10.1038/s41598-019-53755-5. PMID: 31748642; PMCID: PMC6868273.

Bryan-Quirós W, Fernández J, Gutiérrez JM, Lewin MR, Lomonte B.
Neutralizing properties of LY315920 toward snake venom group I and II myotoxic phospholipases A2.
Toxicon. 2019 Jan;157:1-7. doi: 10.1016/j.toxicon.2018.11.292. Epub 2018 Nov 14. PMID: 30447275.

Lewin MR, Gilliam LL, Gilliam J, Samuel SP, Bulfone TC, Bickler PE, Gutiérrez JM.
Delayed LY333013 (Oral) and LY315920 (Intravenous) Reverse Severe Neurotoxicity and Rescue Juvenile Pigs from Lethal Doses of Micrurus fulvius (Eastern Coral Snake) Venom.
Toxins (Basel). 2018 Nov 17;10(11):479. doi: 10.3390/toxins10110479. PMID: 30453607; PMCID: PMC6265968.

Lewin MR, Gutiérrez JM, Samuel SP, Herrera M, Bryan-Quirós W, Lomonte B, Bickler PE, Bulfone TC, Williams DJ.
Delayed Oral LY333013 Rescues Mice from Highly Neurotoxic, Lethal Doses of Papuan Taipan (Oxyuranus scutellatus) Venom.
Toxins (Basel). 2018 Sep 20;10(10):380. doi: 10.3390/toxins10100380. PMID: 30241297; PMCID: PMC6215158.

Bulfone TC, Samuel SP, Bickler PE, Lewin MR.
Developing Small Molecule Therapeutics for the Initial and Adjunctive Treatment of Snakebite.
J Trop Med. 2018 Jul 30;2018:4320175. doi: 10.1155/2018/4320175. PMID: 30154870; PMCID: PMC6091453.

Herzel BJ, Samuel SP, Bulfone TC, Raj CS, Lewin M, Kahn JG.
Snakebite: An Exploratory Cost-Effectiveness Analysis of Adjunct Treatment Strategies.
Am J Trop Med Hyg. 2018 Aug;99(2):404-412. doi: 10.4269/ajtmh.17-0922. Epub 2018 May 31. PMID: 29869597; PMCID: PMC6090346.

Sasidaran MN, Samuel SP, ChinnaRaju S, Antonysamy M, Bulfone TC, Lewin MR.
Parotid swelling after Russell's viper envenomation: an unusual and poor prognostic sign.
Clin Case Rep. 2017 Dec 21;6(2):262-266. doi: 10.1002/ccr3.1105. PMID: 29445459; PMCID: PMC5799621.

Lewin M, Samuel S, Merkel J, Bickler P.
Varespladib (LY315920) Appears to Be a Potent, Broad-Spectrum, Inhibitor of Snake Venom Phospholipase A2 and a Possible Pre-Referral Treatment for Envenomation.
Toxins (Basel). 2016 Aug 25;8(9):248. doi: 10.3390/toxins8090248. PMID: 27571102; PMCID: PMC5037474.

Lewin MR, Samuel SP, Wexler DS, Bickler P, Vaiyapuri S, Mensh BD.
Early Treatment with Intranasal Neostigmine Reduces Mortality in a Mouse Model of Naja naja (Indian Cobra) Envenomation.
J Trop Med. 2014;2014:131835. doi: 10.1155/2014/131835. Epub 2014 May 14. PMID: 24955095; PMCID: PMC4052076.

Lewin MR, Bickler PE, Heier T, Feiner J, Montauk L, Mensh B.
Reversal of Experimental Paralysis in Human by Intranasal Neostigmine Aerosol Suggests a Novel Approach to the Early Treatment of Neurotoxic Envenomation.
Clin. Case Rep. 2013 Oct;1(1):7-15. doi: 10.1002/ccr3.3. Epub 2013 Jul 24. PMID: 25356201; PMCID: PMC4184533.

​Climate and catastrophic illness

Li Y, Du T, Lewin MR, Wang H, Ji X, Zhang Y, Xu T, Xu L.
The Seasonality of Acute Coronary Syndrome and its Relations with Climatic Parameters.
Am J Emerg Med. 2010 Apr; doi.org/10.1016/j.ajem.2010.02.027

Li Y, Du T, Lewin MR, Wang H, Ji X, Zhang Y, Xu T, Xu L.
Circadian, Day-of-Week, and Age Patterns of the Occurrence of Acute Coronary Syndrome in Beijing’s Emergency Medical Services System.
Am J Emerg Med. 2010 Jul;28(6):663-7. doi: 10.1016/j.ajem.2009.02.033

Du T, Lewin MR, Wang H, Ji X, Bohn HH, Xu T, Xu L, Zhang Y, Li Y.
Circadian and Seasonal Rhythms of Acute Upper Gastrointestinal Bleeding in Beijing.
Emerg Med J. 2010 Jul;27(7):504-7. doi: 10.1136/emj.2009.075820.

Du T, Zhang Y, Wu JS, Wang H, Ji X, Xu T, Li Y, Xu L, Lewin MR.
Domicile-Related Carbon Monoxide Poisoning In Cold Months and its Relation With Climatic Factors.
AM J Emerg Med. 2010 Oct; 28(8):928-32. doi: 10.1016/j.ajem.2009.06.019

Expedition medicine and global health

Tonna JE, Balanoff AM, Lewin MR, Saandari N, Wintermark M.
Potentially Low Cost Solution to Extend Use of Early Generation Computed Tomography
Western Journal of Emergency Medicine 2010 Dec; http://www.escholarship.org/uc/item/41j3j93x

Tonna JE, Lewin MR*, Mensh B.
A Case and review of Noma
PLOS 2010 Dec; doi.org/10.1371/journal.pntd.0000869

Tonna JE, Lewin MR*, Hahn I, Platts-Mills TF, Norell MA.
A Prospective, Multi-Year Analysis of Illness and Injury During Summer Travel to Arid Environments.
Wilderness & Environmental Medicine. 2009 Jun; doi.org/10.1580/08-WEME-OR-193R3.1

Wang H, Xu T, Lewin MR.
Future Possibilities for the Treatment of Septic Shock with Herbal Components.
Am J Emerg Med. 2009 Jan; doi.org/10.1016/j.ajem.2008.08.003

Platts-Mills TF,Stendell E, Lewin MR*, Moya MN, Stroh G, Shalit M.
An experimental study of warming intravenous fluid in a cold environment
Wilderness Environ Med 2007 Sept;doi.org/10.1580/06-WEME-OR-051R1.1

Platts-Mills TF, Lewin MR*, Wells J, Bickler P.
Improvised cricothyrotomy provides reliable airway access in an unembalmed human cadaver model
Wilderness Environ Med 2006;doi.org/10.1580/PR20-05.1

Lewin MR*, Knott P, Lo M.
Seal finger
Lancet 2004, doi.org/10.1016/S0140-6736(04)16768-8

Lewin MR*, Musher DM.
Spotted-fever-group rickettsioses in north Asia
Lancet 2004 Mar;doi.org/10.1016/S0140-6736(04)15853-4

Lewin MR*, Kuhn B.
The Gobi Desert medical kit
The Lancet. 2003 Dec; doi.org/10.1016/S0140-6736(03)15053-2

Lewin MR*, Bouyer DH, Walker DH, Musher, DM.
Rickettsia sibirica infection in members of scientific expeditions to northern Asia
Lancet 2003, doi.org/10.1016/S0140-6736(03)14515-1

Lewin MR*, Weinert MF.
An eighty-four-year-old man with fever and painless jaundice: a case report and brief review of Clonorchis sinensis infection
J Travel Med 1999, doi.org/10.1111/j.1708-8305.1999.tb00860.x

Lewin MR*, Green LK, Musher DM.
A solitary pulmonary nodule in a long-term smoker
Hosp Pract 1997, doi: 10.1080/21548331.1997.11443494

Book Chapters

Lewin MR*, Samuel SP.
Abdominal Aortic Aneurysm.
In Clinical Practice of Emergency Medicine, 7^th ed.; Wolfson, A., Lippincott Williams & Wilkins: 2020; Vol. 1, pp 330-333. (see also 2005 4^th edition and 6^th edition 2014)

Lipnick M, Lewin MR*.
Wilderness preparation, equipment and supplies
In Wilderness Medicine, 7^th ed.; Auerbach P. Elsevier: New York, 2017 (see also 2007 5^th ed and 2011 6^th ed)

Tonna EJ, Bohn HH, Lewin MR*.
Methylene Blue Joint Infection
Chapter 78 in Emergency Medicine Procedures, 2^nd ed. Mc Graw Hill Education, 2013

Blau A, Ward D, Lewin MR*.
Fever in the Returning Traveler
Chapter 52 in Emergency Management of Infectious Diseases, 1^st ed. Cambridge Press; 2008

Mallon W, Lewin MR*.
Ectoparasites
Chapter 54 in Emergency Management of Infectious Diseases, 1^st ed. Cambridge Press; 2008