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Published Date: 2018-02-20 21:27:21
Subject: PRO/AH/EDR> Salmonellosis, st I 4,[5],12:b:- - USA: kratom
Archive Number: 20180220.5640222
A ProMED-mail post
ProMED-mail is a program of the
International Society for Infectious Diseases

Date: Tue 20 Feb 2018, 10:30 AM ET
Source: CDC [edited]

Multistate Outbreak of _Salmonella_ I 4,[5],12:b:- Infections Linked to Kratom
CDC, public health and regulatory officials in several states, and the FDA are investigating a multistate outbreak of _Salmonella [enterica_ serotype] I 4,[5],12:b:- infections.

Public health investigators are using the PulseNet system to identify illnesses that may be part of this outbreak. PulseNet is the national subtyping network of public health and food regulatory agency laboratories coordinated by CDC. DNA fingerprinting is performed on _Salmonella_ bacteria isolated from ill people by using techniques called pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS). CDC PulseNet manages a national database of these DNA fingerprints to identify possible outbreaks. WGS gives a more detailed DNA fingerprint than PFGE.

As of [16 Feb 2018], 28 people infected with the outbreak strain of _S._ I 4,[5],12:b:- have been reported from 20 states. A list of the states and the number of cases in each can be found on the Case Count Map page. WGS performed on isolates from ill people were closely related genetically. This means that people in this outbreak are more likely to share a common source of infection.

States / Case Count
Alabama / 1
Arizona / 1
California / 3
Colorado / 1
Florida / 1
Kansas / 1
Kentucky / 1
Louisiana / 1
Massachusetts / 1
Michigan / 1
North Carolina / 2
North Dakota / 1
New York / 1
Ohio / 2
Oklahoma / 2
Oregon / 2
Pennsylvania / 2
South Carolina / 1
Tennessee / 1
Utah / 2
Total / 28

Illnesses started on dates ranging from [13 Oct 2017] to [30 Jan 2018]. Ill people range in age from 6 to 67 years, with a median age of 41. 16 people are male. A total of 11 hospitalizations have been reported. No deaths have been reported.

WGS analysis did not identify any predicted antimicrobial resistance in isolates from 5 ill people. Testing of outbreak isolates using standard antimicrobial susceptibility testing methods is currently underway in CDC's National Antimicrobial Resistance Monitoring System (NARMS) laboratory.

Investigation of the Outbreak
Epidemiologic evidence indicates that kratom is a likely source of this multistate outbreak. Kratom is a plant consumed for its stimulant effects and as an opioid substitute. Kratom is also known as Thang, Kakuam, Thom, Ketom, and Biak.

In interviews, ill people answered questions about the foods they ate and other exposures in the months before they became ill. As many as 8 (73 percent) of 11 people interviewed reported consuming kratom in pills, powder, or tea. No common brands or suppliers of kratom have been identified at this time.

At this time, CDC recommends that people not consume kratom in any form. The investigation indicates that kratom products could be contaminated with _Salmonella_ and could make people sick. CDC's recommendation may change as more information becomes available. This investigation is ongoing and we will provide updates as needed.

Communicated by:

[The following about kratom is from Drugs.com (https://www.drugs.com/illicit/kratom.html)

[Author: L. Anderson, PharmD]

Common or Street Names: Thang, Krypton, Kakuam, Thom, Ketum, Biak-Biak (common name in Thailand)

"What is Kratom?
Kratom (_Mitragyna speciosa_) is a tropical evergreen tree from Southeast Asia and is native to Thailand, Malaysia, Indonesia and Papua New Guinea. Kratom, the original name used in Thailand, is a member of the Rubiaceae family. Other members of the Rubiaceae family include coffee and gardenia. The leaves of kratom are consumed either by chewing, or by drying and smoking, putting into capsules, tablets or extract, or by boiling into a tea. The effects are unique in that stimulation occurs at low doses and opioid-like depressant and euphoric effects occur at higher doses. Common uses include treatment of pain, to help prevent withdrawal from opiates (such as prescription narcotics or heroin), and for mild stimulation. Traditionally, kratom leaves have been used by Thai and Malaysian natives and workers for centuries. The stimulant effect was used by workers in Southeast Asia to increase energy, stamina, and limit fatigue. However, some Southeast Asian countries now outlaw its use.

In the USA, this herbal product has been used as an alternative agent for muscle pain relief, diarrhea, and as a treatment for opiate addiction and withdrawal. However, its safety and effectiveness for these conditions has not been clinically determined, and the FDA has raised serious concerns about toxicity and possible death with use of kratom. As published on 6 Feb 2018, the FDA notes it has no scientific data that would support the use of kratom for medical purposes. In addition, the FDA states that kratom should not be used as an alternative to prescription opioids, even if using it for opioid withdrawal symptoms. As noted by the FDA, effective, FDA-approved prescription medications, including buprenorphine, methadone, and naltrexone, are available from a health care provider, to be used in conjunction with counseling, for opioid withdrawal. Also, they state there are also safer, non-opioid options for the treatment of pain.

DEA Scheduling of Kratom
Kratom was on the DEA's list of drugs and chemicals of concern for several years. On 31 Aug 2016, the DEA published a notice that it was planning to place kratom in Schedule I, the most restrictive classification of the Controlled Substances Act. Its 2 primary active ingredients, mitragynine and 7-hydroxymitragynine (7-HMG), would be temporarily placed onto Schedule I on 30 Sep 2016, according to a filing by the DEA. The DEA reasoning was "to avoid an imminent hazard to public safety. The DEA did not solicit public comments on this federal rule, as is normally done.

However, the scheduling of kratom did not occur on 30 Sep 2016. Dozens of members of Congress, as well as researchers and kratom advocates have expressed an outcry over the scheduling of kratom and the lack of public commenting. The DEA withheld scheduling at that time and opened the docket for public comments. Over 23 000 public comments were collected before the closing date of 1 Dec 2016, according to the American Kratom Association. The American Kratom Association is a lobbying and advocacy group in support of kratom use. The American Kratom Association reports that there are a "number of misconceptions, misunderstandings and lies floating around about Kratom."

As reported by the Washington Post in December 2016, Jack Henningfield, an addiction specialist from Johns Hopkins University and Vice President, Research, Health Policy, and Abuse Liability at Pinney Associates, was contracted by the American Kratom Association to research the kratom's effects. In Henningfield's 127 page report he suggested that kratom should be regulated as a natural supplement, such as St. Johns Wort or Valerian, under the FDA's Food, Drug and Cosmetic Act. The American Kratom Association then submitted this report to the DEA during the public comment period.

Next steps include review by the DEA of the public comments in the kratom docket, review of recommendations from the FDA on scheduling, and determination of additional analysis. Possible outcomes could include emergency scheduling and immediate placement of kratom into the most restrictive Schedule I; routine DEA scheduling in schedule 2 through 5 with more public commenting; or no scheduling at all. The timing for the determination of any of these events is unknown.

State laws have banned kratom use in several states including, Indiana, Tennessee, Wisconsin, Vermont, Arkansas, Alabama and the District of Columbia. These states classify kratom as a schedule I substance. Kratom is also noted as being banned in Sarasota County, Florida, San Diego County, California, and Denver, Colorado. The FDA's analysis from February 2018 included 44 reported deaths associated with the use of kratom. According to Governing.com, legislation was considered last year [2017] in at least 6 other states -- Florida, Kentucky, New Hampshire, New Jersey, New York and North Carolina.

What is the Pharmacology of Kratom?
As reported in February 2018, the FDA has confirmed from analysis that kratom has opioid properties. More than 20 alkaloids in kratom have been identified in the laboratory, including those responsible for the majority of the pain-relieving action, the indole alkaloid mitragynine, structurally related to yohimbine. Mitragynine is classified as a kappa-opioid receptor agonist and is roughly 13 times more potent than morphine. Mitragynine is thought to be responsible for the opioid-like effects.

Kratom, due to its opioid-like action, has been used for treatment of pain and opioid withdrawal. Animal studies suggest that the primary mitragynine pharmacologic action occurs at the mu and delta-opioid receptors, as well as serotonergic and noradrenergic pathways in the spinal cord. Stimulation at post-synaptic alpha-2 adrenergic receptors, and receptor blocking at 5-hydroxytryptamine 2A may also occur. The 7-hydroxymitragynine may have a higher affinity for the opioid receptors. Partial agonist activity may be involved. Additional animals' studies show that these opioid-receptor effects are reversible with the opioid antagonist naloxone.

Time to peak concentration in animal studies is reported to be 1.26 hours, and elimination half-life is 3.85 hours. Effects are dose-dependent and occur rapidly, reportedly beginning within 10 minutes after consumption and lasting from 1 to 5 hours.

Kratom Effects and Actions
Most of the psychoactive effects of kratom have evolved from anecdotal and case reports. Kratom has an unusual action of producing both stimulant effects at lower doses and more CNS depressant side effects at higher doses. Stimulant effects manifest as increased alertness, boosted physical energy, talkativeness, and a more social behavior. At higher doses, the opioid and CNS depressant effects predominate, but effects can be variable and unpredictable. Consumers who use kratom anecdotally report lessened anxiety and stress, lessened fatigue, pain relief, sharpened focus, relief of withdrawal symptoms,

Beside pain, other anecdotal uses include as an anti-inflammatory, antipyretic (to lower fever), antitussive (cough suppressant), antihypertensive (to lower blood pressure), as a local anesthetic, to lower blood sugar, and as an antidiarrheal. It has also been promoted to enhance sexual function. None of the uses have been studied clinically or are proven to be safe or effective. In addition, it has been reported that opioid-addicted individuals use kratom to help avoid narcotic-like withdrawal side effects when other opioids are not available. Kratom withdrawal side effects may include irritability, anxiety, craving, yawning, runny nose, stomach cramps, sweating and diarrhea; all similar to opioid withdrawal.

Deaths reported by the FDA have involved one person who had no historical or toxicologic evidence of opioid use, except for kratom. In addition, reports suggest kratom may be used in combination with other drugs that have action in the brain, including illicit drugs, prescription opioids, benzodiazepines and over-the-counter medications, like the anti-diarrheal medicine, loperamide (Imodium AD). Mixing kratom, other opioids, and other types of medication can be dangerous. Kratom has been shown to have opioid receptor activity, and mixing prescription opioids, or even over-the-counter medications such as loperamide, with kratom may lead to serious side effects.

Extent of Kratom Use
On the Internet, kratom is marketed in a variety of forms: raw leaf, powder, gum, dried in capsules, pressed into tablets, and as a concentrated extract. In the US and Europe, it appears its use is expanding, and recent reports note increasing use by the college-aged population.

The DEA states that drug abuse surveys have not monitored kratom use or abuse in the US, so it's true demographic extent of use, abuse, addiction, or toxicity is not known. However, as reported by the DEA in 2016, there were 660 calls to U.S. poison centers related to kratom exposure from 2010 to 2015.

Kratom Side Effects and Health Hazards
Expected opioid-like side effects that may occur with kratom include:
- Sedation
- Nausea
- Sweating
- Dry mouth
- Increased urination
- Loss of appetite
- Itching
- Constipation
- Dizziness
- Confusion

Case reports describe the following adverse effects from kratom: addiction, withdrawal, hypothyroidism, and liver injury, aching of muscles and bones and jerky limb movements.

Kratom addiction and chronic use has led to cases of psychosis with hallucinations, delusion, and confusion. High-dose use may lead to fast heart rate (tachycardia) and low blood pressure (hypotension). Tremor, anorexia and weight loss are other possible side effects with long-term use.

Seizures have been reported when kratom was combined with modafinil in at least one case report. The DEA has also reported seizure adverse events with recreations kratom use.

A case series from Kronstad, et al. described a fatal drug interaction with kratom. A substance, dubbed "Krypton" - a mixture of mitragynine and a metabolite of tramadol - was found post-mortem in 9 people in Sweden over a one year period. Tramadol, an opioid-like prescription pain drug, was most likely added to kratom to boost its narcotic-like effect.

In November 2017 and February 2018, the FDA issued a public health advisory about deadly risks associated with kratom. There have been 44 reports of Kratom-related deaths, sometimes used in combination with other illicit drugs, prescription drugs, or over-the-counter agents such as loperamide (Imodium).

As with many herbal alternatives, designer drugs, or illicit products sold on the Internet, the possibility exists that kratom may also be contaminated with illegal drugs, black market prescription medications, or even poisonous products. Consumers should avoid buying unknown drug products from the Internet. When combined with other drugs -- recreational, prescription, or alcohol -- the effects of kratom are unknown and may be dangerous.

Is Kratom Addictive?
Kratom is well-known to be addictive, as found with traditional use by natives over many years in Southeast Asian countries. Withdrawal effects similar to narcotic withdrawal and drug-seeking behaviors have been described in users in Southeast Asia. Many Southeast Asian countries have restricted the use of kratom due to the potential for abuse.

The fact that kratom is derived from a plant should not lead consumers to be believe it 100 percent safe and "all-natural". While certainly not all botanicals have dangerous properties, drugs with dangerous effects can come from botanicals, for example, heroin (opium poppy), cocaine (coca leaves), and nicotine (tobacco).

Will a Drug Test Identify Kratom Use?
Currently, kratom is not included in standard drug screens in the US. Kratom tests are available for screening but are not widely available.

Kratom, an herbal product that originated in Southeast Asia, is being used in the US to ease anxiety, treat chronic pain and to reverse opioid withdrawal symptoms; often purchased over the Internet. Recreational use may be on the rise, too. Use in coffee shops has been reported.

The primary psychoactive component, mitragynine, is many times more potent than morphine. DEA lists kratom as a drug and chemical of concern, and is in the process of evaluating kratom for placement into controlled substances scheduling.

Placing kratom into schedule I would place it in the same category as heroin, LSD or marijuana, and prevent access for medical research, a concern for many experts, consumers, and advocacy groups. Lack of quality scientific evidence confounds the evaluation of the safety of kratom. Concerns also exist that the general public would not be able to identify or confirm the quality or purity of kratom from any Internet source.

The FDA has warned consumers not to use any products labeled as containing kratom. As of February 2018, the FDA has reported on 44 related deaths linked with kratom use, often in use with other substances.

Health care professionals and consumers should report any adverse events related to products containing kratom to the FDA's MedWatch program."

and now salmonellosis. - Mod.LL

HealthMap/ProMED-mail map:
United States: http://healthmap.org/promed/p/106]

See Also

Salmonellosis, st Typhimurium - USA: (IA, MN) chicken salad, alert, recall 20180218.5635548
Salmonellosis, st I 4,[5,12:b:- and Newport - USA (02): frozen coconut, recall 20180217.5633342
Salmonellosis - USA (03): (IA) chicken salad, alert, recall 20180214.5628958
Salmonellosis - USA (02): (CO) restaurant, fatal 20180212.5622263
Salmonellosis, st Reading - USA: (MN) children, raw pet food, alert, recall 20180211.5620484
Salmonellosis, st Montevideo - USA: restaurant chain, sprouts 20180121.5574088
Salmonellosis, st I 4,[5,12:b:- and Newport - USA: frozen coconut, alert, recall 20180117.5565073
Salmonellosis - USA : frozen coconut, alert, recall 20180110.5550279
Salmonellosis - USA (16): (GA) turkey source 20171208.5490043
Salmonellosis, st Newport - USA: (WA, OR) precut melon 20171202.5479308
Foodborne illness - USA (08): (GA) salmonella susp 20171122.5459753
Foodborne illness - USA (07): (MD) oyster festival, RFI 20171112.5439742
Salmonellosis, st. Agbeni - USA (02): pet turtles 20171118.5452185
Salmonellosis, st Heidelberg - USA (02): MDR, cattle contact, RFI 20171117.5450807
Salmonellosis - USA (15): raw tuna, alert, recall 20171027.5408123
Foodborne illness - USA (06): (VA) food festival, Salmonella Javiana 20171025.5401877
Salmonellosis - USA (14): (LA) jambalaya, 2nd pathogen Clostridium perfringens 20171024.5401550
Salmonellosis - USA (13): (LA) jambalaya, 2nd pathogen Clostridium perfringens 20171021.5395792
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