MASSACHUSETTS DEPARTMENT OF PUBLIC HEALTH GUIDE TO SURVEILLANCE, REPORTING, AND CONTROL
Botulism

Section 1 
ABOUT THE DISEASE

A. Etiologic Agent

Botulism is caused by exposure to a neurotoxin produced by Clostridium botulinum, and is also produced by some strains of Clostridium butyricum, Clostridium baratii, and Clostridium argentinense.  C. botulinum is an anaerobic (grows in the absence of oxygen), spore-forming bacterium. The toxin is produced as the bacteria are multiplying; the bacteria multiply under anaerobic and neutral or mildly acidic (generally pH>4) conditions. There are seven types of botulinum toxins (A–G), but human botulism is primarily caused by types A, B, and E.  

B. Clinical Description

Botulism is a neuroparalytic illness characterized by symmetric, descending flaccid paralysis of motor and autonomic nerves, beginning with the cranial nerves. C. botulinum toxin is one of the most potent, lethal substances known. The Centers for Disease Control and Prevention (CDC) classifies botulism into five categories: foodborne botulism, wound botulism, infant botulism, adult intestinal toxemia, and iatrogenic botulism. There is a different site of toxin production for each of the forms, but they all share the flaccid paralysis that results from exposure to botulinum toxin.

Foodborne Botulism
 
Foodborne botulism is a severe poisoning caused by the ingestion of pre-formed C. botulinum toxin. The clinical syndrome is dominated by neurologic signs and symptoms, including blurred or double vision, dysphagia (difficulty swallowing), dry mouth, and muscle weakness. Symmetric, descending flaccid paralysis is classic for botulism.  Generally, paralysis first affects the cranial nerves, followed by the upper extremities, the respiratory muscles, and finally, the lower extremities. Patients usually require ventilator support, which is commonly needed for 2–8 weeks. The clinical symptoms are similar no matter which toxin type is responsible for the illness, but type A has been associated with a higher case-fatality rate than types B or E. In general, the case-fatality rate for foodborne botulism is 5–10%. Recovery may take months. 

Wound Botulism

Wound botulism usually presents with the same clinical picture as foodborne botulism. In wound botulism, the organism multiplies in the wound and produces the toxin, which is then absorbed into the bloodstream.

Infant Botulism

In infant botulism, the C. botulinum spores are ingested, and the toxin is formed in the intestines. Older children and adults have mature digestive systems that can move the spores through the digestive track thus preventing the spores from germinating and producing the toxin.  Cases can occur in breastfed infants during the time that the infants are first introduced to non-human milk substances. The earliest clinical sign in infants is constipation, which is followed by poor feeding, decreased sucking, lethargy, listlessness, ptosis (drooping eyelids), difficulty swallowing, a weak cry, and lack of muscle tone, giving rise to the term “floppy baby syndrome.” In some cases, respiratory insufficiency and respiratory arrest may occur. Infant botulism presents with a wide range of severity, from mild illness to sudden death. Some studies suggest that infant botulism may be responsible for up to 5% of cases of Sudden Infant Death Syndrome (SIDS). 

Adult Intestinal Toxemia

Adult intestinal toxemia is a very rare disease and occurs similarly to infant botulism, when the spores are ingested and the toxin is formed in the intestines. Although adult intestinal toxemia is not well understood, it typically occurs in adults who have altered intestinal flora due to antimicrobial use or because of gastrointestinal tract abnormalities.

Iatrogenic Botulism

Iatrogenic botulism can occur if too much toxin is injected. Toxin can be injected for cosmetic reasons as well as medical reasons. Laboratory confirmed cases have occurred after injection of high doses of unapproved botulinum toxin product. 
 
C. Vectors and Reservoirs

C. botulinum spores are ubiquitous in soil worldwide. The spores are frequently recovered from agricultural products, including honey and vegetables, and are also found in dust, soil, lake and marine sediments, and intestinal tracts of animals including fish. 

D. Modes of Transmission

Foodborne botulism is acquired by ingesting pre-formed toxin. This usually occurs as a result of ingesting food that has been inadequately processed and then inadequately prepared before being eaten. The most frequent source is homemade foods that have been improperly canned, preserved, or fermented. Outbreaks have also been attributed to baked potatoes in foil, minced garlic in oil, Alaskan salmon products, and sautéed onions held under a layer of butter. Tomato and similar food products, once thought to be a low-risk food due to a low pH, can no longer be dismissed as a potential vehicle because microenvironments in the food product can allow growth of C. botulinum. The toxin is heat labile and can be destroyed by boiling. 

Wound botulism occurs when wounds are contaminated with dirt or gravel containing botulism spores. Persons who inject drugs are at a greater risk for getting wound botulism.

Infant botulism and adult intestinal toxemia occur as a result of ingesting the spore form of the bacteria, which then goes on to germinate and produce toxins in the intestines. This can happen through ingestion of food, soil, or dust contaminated with botulinum spores. Honey often contains C. botulinum spores and infant botulism has classically been associated with ingestion of honey. However, this has become quite rare and most cases are thought to be associated with ingestion of dust or soil containing C. botulinum spores. Some cases of intestinal botulism have occurred in infants living in areas of construction and earth disruption. Infant botulism is the most common form of botulism in the U.S.

Iatrogenic botulism occurs if too much botulinum toxin is injected during a cosmetic or other medical procedure.

E. Incubation Period

The incubation period is variable, but neurologic symptoms of foodborne botulism usually appear within 12–72 hours (ranging from 2 hours to 8 days) after eating contaminated food. For wound botulism, the incubation period is generally longer ranging from 4-14 days. The incubation period for infant botulism is estimated to be 3 to 30 days. The incubation period for adult intestinal toxemia is unknown since it is usually not known when the spores were ingested. The incubation period for iatrogenic botulism is unclear.

F. Period of Communicability or Infectious Period

No instances of person-to-person spread have ever been documented for botulism. 

G. Epidemiology

Botulism occurs worldwide as sporadic cases and as family and general outbreaks. During the period of 2011-2015, there were 125 annual average cases of infant botulism. During 2011-2014 there were 15 annual average cases of foodborne botulism and 13 annual average cases of wound botulism. According to the CDC’s National Botulism Surveillance Summary, a total of 205 confirmed botulism cases were reported in 2016— 149 (73%) infant, 29 (14%) foodborne, 24 (12%) wound, and 3 (1%) of unknown etiology.  

H. Bioterrorist Potential

C. botulinum toxins are listed by the CDC as Category A bioterrorist agents. If acquired and properly disseminated, botulinum toxin could cause a serious public health challenge in terms of ability to limit the number of casualties and to control repercussions of such an attack. 

Section 2
REPORTING CRITERIA AND LABORATORY TESTING

A. What to Report to the Massachusetts Department of Public Health (MDPH)

Report any suspicion of botulism that is called to your attention. This could take the form of a health care provider or laboratory inquiring about botulism or botulism testing. Also report any suspected exposure to C. botulinum that could represent bioterrorism. Currently the Massachusetts State Public Health Laboratory (MA SPHL) does not offer testing for botulism. All specimens are currently being sent to the Wadsworth Center, New York Department of Health through the MA SPHL. 

Note: See Section 3C for information on how to report a case.

B. Laboratory Testing Services Available

The MA SPHL will facilitate sending specimens for testing to the Wadsworth Center.  The Wadsworth Center offers culture, PCR, mouse bioassay, as well as testing of food specimens. Testing for the presence of both C. botulinum and botulinum toxin will occur only if epidemiologically and clinically indicated. Prior approval for testing must be obtained from the MDPH Division of Epidemiology & Immunization at (617) 983-6800. For more information on testing and specimen submission, call the MA SPHL Enteric Laboratory at (617) 983-6609.

Section 3
REPORTING RESPONSIBILITIES AND CASE INVESTIGATION

A. Purpose of Surveillance and Reporting

•	To assist in the diagnosis and treatment of potential cases.
•	To identify sources of public health concern (e.g., a commercially-distributed food product), and to stop transmission from such a source.
•	To classify reported cases properly as foodborne, wound, infant, adult intestinal toxemia, and iatrogenic botulism.
•	To identify cases and clusters of human illness that may be associated with a bioterrorist event.

B. Laboratory and Health Care Provider Reporting Requirements

Botulism is reportable to local boards of health (LBOH). The MDPH requests that health care providers immediately report to the LBOH in the community where the case is diagnosed, all confirmed or suspect cases of botulism, as defined by the reporting criteria in Section 2A.

Due to the rarity and potential severity of botulism, the MDPH requests that information about any suspect or known case of botulism, or any suspected exposure that may be bioterrorist in nature, be immediately reported to the LBOH in the community where the case is suspected or diagnosed.  If this is not possible, call the MDPH Division of Epidemiology and Immunization at (617) 983-6800 (any time of day or night). Since botulism testing is only available at the Wadsworth Center, the MDPH must be informed to approve appropriate testing.

C. Local Board of Health Reporting and Follow-Up Responsibilities

Reporting Requirements

MDPH regulations (105 CMR 300.110) stipulate that botulism is reportable to the LBOH and that each LBOH must report any case of botulism or suspect case of botulism, as defined by the reporting criteria in Section 2A. However, since confirmatory testing is only available at the Wadsworth Center in New York and must be approved by the MDPH Division of Epidemiology and Immunization, it is unlikely a LBOH would be notified of a confirmed case without the prior knowledge of MDPH.  However, a LBOH could be the initial recipient of a report of a suspect case.  Cases reported directly to MDPH by providers or laboratories will populate the MAVEN “Online LBOH Notification for Immediate Disease” workflow for acknowledgement by the appropriate LBOH.  Suspect cases not already in MAVEN should be reported by phone to the MDPH Division of Epidemiology and Immunization at (617) 983-6800. Each case shall be reported immediately, but no later than 24 hours after receipt by the LBOH.  
The most up-to-date reporting requirements can be found at:
http://www.mass.gov/eohhs/gov/departments/dph/programs/id/epidemiology/rdiq/reporting-diseases-and-surveillance-information.html

Case Investigation

The most important thing a LBOH can do upon learning of a suspect case of botulism, or any suspected exposure that may be bioterrorist in nature, is to immediately call the MDPH Division of Epidemiology and Immunization, any time of day or night, at (617) 983- 6800. 
Using MAVEN
Administrative Question Package
Monitor your “Online LBOH Notification for Immediate Disease” workflow in MAVEN for any new cases of
botulism. An MDPH Epi-of-the-Day (EOD) will review all new cases and initiate immediate follow-up for botulism events. Depending on local capacity, EODs may take the lead for case investigation and will coordinate follow-up with the LBOH as needed. Once a new event appears in this workflow, open the Administrative Question Package (QP) and under the “Local Health and Investigation” section, answer the first question “Step 1 – LBOH acknowledged” by selecting “Yes.” The “LBOH acknowledged date” will auto populate to the current day. Completing this first step will move the event out of this workflow and into your “Online LBOH notified but Case Report Forms (CRF) are pending” workflow. Navigate through different question packages in MAVEN to answer relevant questions and additional information as outlined in this section below.  Note the date you started your investigation by answering “Step 2 – Investigation started” as “Yes” and then note the date where shown. Record your name, agency, and phone numbers where shown in “Step 3 - LBOH/Agency Investigator.”

Demographic Question Package
Record all demographic and employment information. 

Clinical Question Package
Complete the “Clinical Information” section, providing symptom and other relevant medical information asked of in the clinical question package. 

Vaccine and IG Information Question Package
If the case has been vaccinated for botulism or has had a recent influenza vaccination,  enter the vaccine name, dose and date of administration, and other relevant information. 

Risk/Exposure/Control & Prevention Question Package
Accurately record all risk questions- history of travel including travel dates and destinations, exposure to soil, and history of tick bites.

Completing Your Investigation 

If you were able to complete a case investigation and follow-up is complete, mark “Step 4 – Case
Report Form Completed” as “Yes” and then choose “Local Board of Health (LBOH) –Ready for MDPH review” for the “Completed by” variable.

If you and/or the EOD leading the case investigation have made several attempts to obtain case information but have been unsuccessful (e.g., the case or health care provider does not return your calls or respond to a letter, or the case refuses to divulge information or is too ill to be interviewed), please fill out the question packages with as much information as you have gathered, and then complete “Step 4 - Case Report Form Completed” as “No” and choose a primary reason why the case investigation was not completed from the choices provided in the primary reason answer variable list.

Case investigations of botulism in Massachusetts residents will be directed by the MDPH Division of Epidemiology and Immunization. If a bioterrorist event is suspected, the MDPH and other response authorities will work closely with the LBOH and will provide instructions/information on how to proceed.

Following immediate notification of the MDPH, the LBOH may be asked to assist in investigating any case(s) of botulism. Use the guidelines listed on the next page to assist in the investigation. 

All botulism cases are treated with urgency in order to work with clinicians to obtain the antitoxin or Human Botulism Immune Globulin (BabyBIG) to patients if warranted as well as identify a source of exposure.

Foodborne Botulism

The source of the intoxication and other potentially exposed persons must be identified. The case must be interviewed concerning possible food sources. In most cases, this information will need to be obtained from family members or from other close contacts, since the case will most likely not be in a condition to be interviewed. Use the MDPH Foodborne Illness Complaint Worksheet, found online at https://www.mass.gov/files/documents/2016/07/nf/foodborne-ill-worksheet.pdf  to facilitate recording information pertinent to foodborne transmission. Please call the MDPH Center for Environmental Health, Food Protection Program (FPP) at (617) 983-6712 for assistance in determining possible food sources. Use the following guidelines to assist in the investigation:

•	Identify all home-canned foods eaten during the week prior to symptoms. The most suspect foods are those eaten less than two days before onset and those that were not eaten by other well persons. Keep in mind that some cases may experience less severe symptoms with a later onset than the case.

•	Identify all commercially canned foods eaten during the week prior to the onset of illness. For implicated foods, determine the brand, manufacturer, package size, lot number, and place and date of purchase.

•	Identify all sausage and other preserved meats eaten during the week prior to onset of illness. Meat products that have not been adequately refrigerated are also suspect.

•	Identify all smoked or otherwise preserved fish eaten during the week before onset of symptoms.

•	Identify other potentially exposed persons. Other persons who have eaten implicated food must be reached as soon as possible and advised to seek health care immediately. Depending on the time of ingestion, other exposed persons might be candidates for treatment with purgatives, and at the very least, should be under close medical supervision.

•	Obtain the name, address, and telephone number of every person who may have eaten the suspect food item.

•	Obtain the name, address, and telephone number of every person who may have the suspect home processed food in his or her possession.

•	Remove implicated food items from the environment for testing. The FPP, at (617) 983-6712, will coordinate pick-up and testing of food samples. If a commercial product is suspected, the FPP will also coordinate follow-up with relevant outside agencies.

Wound botulism

No follow-up required.

Infant botulism

Ask the infant’s caretakers about honey consumption. Otherwise, extensive epidemiological follow-up is not usually required. Education should be provided regarding prevention.

Botulism Testing: In all suspect cases of botulism, a determination is made by the MDPH Division of Epidemiology and Immunization, the case’s health care provider, and the Foodborne and Diarrheal Branch at CDC based on available clinical and epidemiological data, about the appropriateness of botulism testing. Arrangements will then be made for the submission of appropriate specimens.

Botulism Antitoxin: Equine-derived heptavalent botulinum antitoxin therapy (BAT) is only administered to adult patients with foodborne or wound botulism. Equine-derived heptavalent botulinum antitoxin (BAT) may cause serum sickness in approximately 20% of treated persons and is not indicated in cases of infant botulism. The health care provider, in consultation with the MDPH Division of Epidemiology and Immunization and the Foodborne and Diarrheal Branch at CDC, must determine the need for antitoxin therapy. The CDC must release and approve its use. If needed, antitoxin will be immediately flown into the airport closest to the hospital where the case is being treated. The decision to administer antitoxin must be made immediately and the LBOH should be prepared to assist with logistical arrangements. Since testing for the presence of toxin or bacteria in clinical specimens can take many days, the decision to administer antitoxin cannot wait for testing to confirm the intoxication.

Human Botulism Immune Globulin (BabyBIG®):  BabyBIG® is approved (licensed) by the U.S. Food and Drug Administration (FDA) for the treatment of infant botulism types A and B.  It consists of human-derived anti-botulism toxin antibodies and is made and distributed by the California Department of Public Health under the proprietary name of BabyBIG® and available 24/7. To obtain BabyBIG® for a patient with suspect infant botulism, the physician must contact the Infant Botulism Treatment and Prevention Program (IBTPP) on-call physician at (510) 231-7600 (24/7/365).
Completing your Investigation
1.	If you were able to complete a case investigation and follow-up is complete, mark “Step 4 – Case Report Form Completed” as “Yes” and then choose Local Board of Health (LBOH) –Ready for MDPH review for the Completed by variable. 
2.	If you have made several attempts to obtain case information but have been unsuccessful (e.g., the case or health care provider does not return your calls or respond to a letter, or the case refuses to divulge information or is too ill to be interviewed), please complete “Step 4 - Case Report Form Completed” as “No” and then choose a primary reason why the case investigation was not completed from the choices provided in the primary reason answer variable list.
3.	If you are not online for MAVEN you may submit a paper case report form. After completing the form, attach laboratory report(s) and fax or mail (in an envelope marked “Confidential”) to ISIS. The confidential fax number is (617) 983-6813. Call ISIS at (617) 983-6801 to obtain a copy of the case report form and to confirm receipt of your fax.

The mailing address is:
MDPH, Office of Integrated Surveillance and Informatics Services (ISIS)
305 South Street, 5th Floor
Jamaica Plain, MA 02130
Fax: (617) 983-6813

Section 4
CONTROLLING FURTHER SPREAD

A. Isolation and Quarantine Requirements (105 CMR 300.200)

None

Minimum Period of Isolation of Patient 

None

Minimum Period of Quarantine of Contacts

None  

B. Protection of Contacts of a Case

None

C. Managing Special Situations

Reported Incidence Is Higher Than Usual/Outbreak Suspected

Any case of botulism must be investigated to determine the source of infection and the mode of transmission. See Section 3C for the proper response to a suspect or confirmed case of botulism. 

Note: Refer to the MDPH Foodborne Illness Investigation and Control Reference Manual for comprehensive information on investigating foodborne illness complaints and outbreaks. It is available in pdf format at https://www.mass.gov/lists/foodborne-illness-investigation-and-control-manual  For the most recent changes to the Massachusetts Food Code, contact the FPP at (617) 983-6712 or through the MDPH website at www.mass.gov/dph/fpp  

If a bioterrorist event is suspected, the MDPH and other response authorities will work closely with the LBOH and will provide instructions/information on how to proceed.

D. Preventive Measures

Environmental Measures

To avoid future exposures, recommend that individuals:

•	Be educated about the proper time, pressure, and temperature required to destroy spores, if they are interested in home-canning and other preservation techniques. More information can be obtained from the FPP.

•	Not open bulging containers and not eat or even “taste-test” foods with off odors.

•	Not feed honey to children <1 year old.

A Botulism Public Health Fact Sheet is available at https://www.mass.gov/service-details/botulism 

ADDITIONAL INFORMATION

The following is the formal CDC surveillance case definition for botulism. It is provided for your information only and should not affect the investigation or reporting of a case that fulfills the criteria in Section 2A of this chapter. (The CDC and the MDPH use the CDC case definitions to maintain uniform standards for national reporting.) For reporting to the MDPH, always use the criteria outlined in Section 2A.

Note: The most up-to-date CDC case definitions are available on the CDC website at https://wwwn.cdc.gov/nndss/conditions/

Laboratory Criteria for Diagnosis

Foodborne

Detection of botulinum toxin in serum, stool, or patient’s food, or isolation of C. botulinum from stool.

Infant

Detection of botulinum toxin in stool or serum, or isolation of C. botulinum from stool.

Wound

Detection of botulinum toxin in serum, or isolation of C. botulinum from a wound.

Other

Detection of botulinum toxin in a clinical specimen, or isolation of C. botulinum from a clinical specimen.

Confirmed Case Definition

Foodborne

A clinically compatible case that is laboratory-confirmed or that occurs among persons who ate the same food as persons who have laboratory-confirmed botulism (see Laboratory Criteria section for more information).

Infant

A clinically compatible case that is laboratory-confirmed occurring in a child aged less than 1 year.

Wound

A clinically compatible case that is laboratory-confirmed in a patient who has no suspected exposure to contaminated food and who has a history of a fresh, contaminated wound during the two weeks before onset of symptoms or a history of injection drug use within the 2 weeks before onset of symptoms.

Other

A clinically compatible case that is laboratory-confirmed in a patient aged great than or equal to 1 year who has no history of ingestion of suspect food and has no wounds.

REFERENCES

American Academy of Pediatrics. [Botulism and Infant Botulism] In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2018-2021 Report of the Committee on Infectious Diseases, 31st Edition. Itasca, IL: American Academy of Pediatrics; 2018: 283-286

“Botulism.” Centers for Disease Control and Prevention. October 25, 2017. https://www.cdc.gov/botulism/index.html 

“Clostridium botulinum: Frequently Asked Questions.” Centers for Disease Control and Prevention. October 6, 2005. www.cdc.gov/ncidod/dbmd/diseaseinfo/botulism_g.htm 

Heymann, D., ed. Control of Communicable Diseases Manual, 20th Edition. Washington, DC, American Public Health Association, 2015.

MDPH. Foodborne Illness Investigation and Control Reference Manual. Massachusetts Department of Public Health. 2017. < https://www.mass.gov/lists/foodborne-illness-investigation-and-control-manual> 

MDPH. Regulation 105 CMR 300.000: Reportable Diseases, Surveillance, and Isolation and Quarantine Requirements. MDPH, Promulgated January 27, 2017

“National Botulism Surveillance Summary 2016.” Centers for Disease Control and Prevention. December 2017. <https://www.cdc.gov/botulism/pdf/Botulism-2016-SUMMARY-508.pdf.>

Shapiro, Roger L., et al. Botulism in the United States: A Clinical and Epidemiologic Review. Ann Internal Med. August 1, 1998; 129(3): 221–228.