Every day, individuals worldwide are acutely and chronically poisoned with organophosphate (OP) pesticides. As a group, organophosphates (OP) represent the largest volume of pesticides used worldwide (e.g., chlorpyrifos, malathion, diazinon, etc.).  According to the EPA, 20 million pounds of organophosphate pesticides were used in the US in 2012.  Several hundred OP pesticides exist and as of 2015, the EPA listed 36 OPs registered for use in the US.  The World Health Organization estimates approximately 3,000,000 acute OP pesticide poisonings per year worldwide with 300,000 deaths.  But the WHO also states that there is no good tracking system in place and that many go unreported.  With ~1.8 billion agricultural workers worldwide, most of whom use pesticides, the actual number may be considerably higher.  On the average, seven pesticide applications on crops are performed per year.  With the OP pesticide class representing about one third of all insecticides in use, a good percentage of the 1.8 billion agricultural workers worldwide are chronically being exposed to these pesticides. 

OPs are also incorporated into flame retardants and plasticizers (PFRs) which are a group of chemicals widely added to consumer products and growing in use. Recently in the news, Aerotoxic Syndrome in airline pilots and crews is caused by OPs used in aviation lubricants.  For proper treatment, accurate diagnosis is imperative. Unfortunately a number of clinical situations can mimic symptoms of OP poisoning (e.g., nicotine, mushroom poisoning, botulism, etc.). 

Exposure to organophosphate pesticides has been associated with increased incidence of dementia and Alzheimer’s disease. (Paul 2018, Jokanovic 2018, Lin 2015, Hayden 2010, etc.).  In the US there are currently 5.7 million cases of Alzheimer’s disease.  This number is projected to grow to 7.1 million cases by 2025 and to 13.8 million by 2050.  The current annual cost burden on the US healthcare system to care for Alzheimer’s patients is $277 billion.  Projections state this cost burden to grow to $1.1 trillion annually by 2050.  A rapid, easy to use diagnostic point of care test that can reliably detect acute and chronic OP pesticide exposure would allow affected individuals to be quickly identified and removed from the toxic environment and properly treated.

The use of nerve agents as a lethal weapon by radical political groups and unstable governments is a clear and present danger. Starting in the 1980’s, the Iraqi military used tabun against Iran.  In the 1990’s Terrorist group Aum Shinrikyo released sarin in the Matsumoto and Tokyo subways (1990s). (Nozaki H 1995) (Macilwain 1993) (Brown MA 1998) On August 21, 2013 the Syrian Arab Republic utilized sarin in the Ghouta area of Damascus in Syria in 2013 resulting in ~3,600 exposures, 1429 deaths. (Sellstrom A 2013) (The White House 2013)  Since that date, 85 confirmed chemical attacks using chlorine, mustard gas, or nerve agents have occurred; sarin having been confirmed at least 7 times (4 attacks with sarin by Syrian gov’t in 2013*, and attacks on Syria’s Talmenes April 2014*, Sarmin March 2015*, and Ltamenah March 2017* [*UN confirmed] (Kimball D 2018).  At least 50 of the 85 attacks have been confirmed to be carried out by the Syrian government (Watch 2018). Further, evidence strongly suggests that on April 4, 2017, a Syrian government warplane attacked with a nerve agent a town in the northwestern governorate of Idlib, Khan Sheikhoun, killing at least 90 people, 30 of them children (Kimball D 2018). On April 7, 2018, a major chemical weapons attack using sarin occurred in Douma, a suburb outside of Damascus, Syria, killing at least several dozen civilians (Kimball D 2018). On February 13, 2017 North Korea’s Kim Jong-nam was assassinated with highly toxic VX when two women attacked him with the lethal chemical weapon at Kuala Lumpur International Airport in Malaysia (Paddock RC 2017). Further, According to OPCW, Sergei Skripal, a former Russian military officer and double agent for the UK’s intelligence services, and his daughter Yulia Skripal were poisoned in Salisbury, England, with a Novichok nerve agent. (Salisbury attack: Chemical weapons watchdog confirms UK findings on nerve agent 2018) A police officer was also taken into intensive care after being contaminated when he went to Sergei Skripal’s house.  June 30, 2018 Two British nationals in Amesbury, seven miles from Salisbury, were exposed to Novichok, killing one. (Amesbury Novichok poisoning: Couple exposed to nerve agent 2018).

There are more than 8.5 million U.S. and EU military personnel. Military and civilian support personnel are supplied with Mark I Kits (auto-injectors) containing atropine and 2PAM to be used in case of a nerve-gas attack. For civilian response, nerve agent antidotes are carried by EMS first responders and are strategically pre-deployed across the country in large ChemPack containers.  Although these existing antidotes are helpful, substantial improvement is needed to increase survival outcomes and reduce neurological damage from nerve agent exposure.

Homeland Security Scenario #7 anticipates that a nerve agent attack event would produce 6,000 casualties with tens of thousands of individuals requiring monitoring and decontamination.