Global & Disaster Medicine

Archive for the ‘Botulism’ Category

CDC recommendations to healthcare providers treating patients in Puerto Rico and USVI, as well as those treating patients in the continental US who recently traveled in hurricane-affected areas during the period of September 2017 – March 2018.

CDC

Advice for Providers Treating Patients in or Recently Returned from Hurricane-Affected Areas, Including Puerto Rico and US Virgin Islands

Distributed via the CDC Health Alert Network
October 24, 2017, 1330 ET (1:30 PM ET)
CDCHAN-00408

Summary
The Centers for Disease Control and Prevention (CDC) is working with federal, state, territorial, and local agencies and global health partners in response to recent hurricanes. CDC is aware of media reports and anecdotal accounts of various infectious diseases in hurricane-affected areas, including Puerto Rico and the US Virgin Islands (USVI). Because of compromised drinking water and decreased access to safe water, food, and shelter, the conditions for outbreaks of infectious diseases exist.

The purpose of this HAN advisory is to remind clinicians assessing patients currently in or recently returned from hurricane-affected areas to be vigilant in looking for certain infectious diseases, including leptospirosis, dengue, hepatitis A, typhoid fever, vibriosis, and influenza. Additionally, this Advisory provides guidance to state and territorial health departments on enhanced disease reporting.

 

Background
Hurricanes Irma and Maria made landfall in Puerto Rico and USVI in September 2017, causing widespread flooding and devastation. Natural hazards associated with the storms continue to affect many areas. Infectious disease outbreaks of diarrheal and respiratory illnesses can occur when access to safe water and sewage systems are disrupted and personal hygiene is difficult to maintain. Additionally, vector borne diseases can occur due to increased mosquito breeding in standing water; both Puerto Rico and USVI are at risk for outbreaks of dengue, Zika, and chikungunya.

Health care providers and public health practitioners should be aware that post-hurricane environmental conditions may pose an increased risk for the spread of infectious diseases among patients in or recently returned from hurricane-affected areas; including leptospirosis, dengue, hepatitis A, typhoid fever, vibriosis, and influenza. The period of heightened risk may last through March 2018, based on current predictions of full restoration of power and safe water systems in Puerto Rico and USVI.

In addition, providers in health care facilities that have experienced water damage or contaminated water systems should be aware of the potential for increased risk of infections in those facilities due to invasive fungi, nontuberculous Mycobacterium species, Legionella species, and other Gram-negative bacteria associated with water (e.g., Pseudomonas), especially among critically ill or immunocompromised patients.

Cholera has not occurred in Puerto Rico or USVI in many decades and is not expected to occur post-hurricane.

 

Recommendations

These recommendations apply to healthcare providers treating patients in Puerto Rico and USVI, as well as those treating patients in the continental US who recently traveled in hurricane-affected areas (e.g., within the past 4 weeks), during the period of September 2017 – March 2018.

  • Health care providers and public health practitioners in hurricane-affected areas should look for community and healthcare-associated infectious diseases.
  • Health care providers in the continental US are encouraged to ask patients about recent travel (e.g., within the past 4 weeks) to hurricane-affected areas.
  • All healthcare providers should consider less common infectious disease etiologies in patients presenting with evidence of acute respiratory illness, gastroenteritis, renal or hepatic failure, wound infection, or other febrile illness. Some particularly important infectious diseases to consider include leptospirosis, dengue, hepatitis A, typhoid fever, vibriosis, and influenza.
  • In the context of limited laboratory resources in hurricane-affected areas, health care providers should contact their territorial or state health department if they need assistance with ordering specific diagnostic tests.
  • For certain conditions, such as leptospirosis, empiric therapy should be considered pending results of diagnostic tests— treatment for leptospirosis is most effective when initiated early in the disease process. Providers can contact their territorial or state health department or CDC for consultation.
  • Local health care providers are strongly encouraged to report patients for whom there is a high level of suspicion for leptospirosis, dengue, hepatitis A, typhoid, and vibriosis to their local health authorities, while awaiting laboratory confirmation.
  • Confirmed cases of leptospirosis, dengue, hepatitis A, typhoid fever, and vibriosis should be immediately reported to the territorial or state health department to facilitate public health investigation and, as appropriate, mitigate the risk of local transmission. While some of these conditions are not listed as reportable conditions in all states, they are conditions of public health importance and should be reported.

 

For More Information


California: An outbreak of botulism linked to the consumption of ready-to-eat nacho cheese

 

California Department of Public Health

MEMORANDUM DATE: September 6, 2017
TO: Directors of Environmental Health
FROM: California Department of Public Health (CDPH), Food and Drug Branch (FDB)
SUBJECT: Nacho cheese warming units at retail locations

 

The CDPH Food and Drug Branch (FDB) and Sacramento County Environmental Management Department (SCEMD) recently investigated an outbreak of botulism linked to the consumption of ready to eat nacho cheese purchased at Valley Oak Food and Fuel in Walnut Grove, California. The nacho cheese was applied to chips by customers from a counter-top, self-service warming and dispensing unit supplied by the cheese manufacturer. These types of warming and dispensing units are typically designed to maintain the cheese at approximately 140 deg. F.

As of May 31, 2017, a total of 10 case-patients were laboratory-confirmed with C. botulinum toxin type A. All patients were hospitalized; nine were in an intensive care unit, seven required ventilator support, and one died. Leftover nacho cheese sauce collected from the gas station yielded C. botulinum toxin type A bacteria and toxin. Due to the extensive distribution of the same lot code of nacho cheese throughout the United States without additional botulism cases, internal testing conducted by the Wisconsin manufacturer of the nacho cheese, and only a single bag of cheese linked to human illness, FDB and SCEMD suspect the nacho cheese was likely contaminated at the retail location. A few items in particular were noted during the investigation that was concerning:

 The 5 pound bag of nacho cheese collected at the retail location on May 5, 2017 was being used past the “Best By” date.

 Records were not being maintained by the gas station employees indicating when the bag of nacho cheese was originally added to the warming unit.

 The plastic tool designed to open the bags of cheese (provided with the nacho cheese warming and dispensing unit) was not being used by employees.

FDB is aware that these types of nacho cheese warming and dispensing units are in use at many retail locations throughout California. These units generally provide safe, ready-to-eat foods without significant input from employees at each location. FDB would like to provide the following guidance regarding the use of nacho cheese warming and dispensing units in retail locations.

1. Management and employees should follow the instructions for each type of machine and product they use. Instructions for use may be included on the packaging of the

 

bagged nacho cheese or included on the interior panels of the warming and dispensing unit. These directions may include pre-heating and the length of time a product can remain at elevated holding temperatures. In some cases the product may only be held above 135 deg. F. for 4-6 days.

2. Management should ensure that records are maintained indicating when bagged cheese was last changed. This may be accomplished by writing the date the product was added to the warmer on the bag itself.

3. Management should ensure that the warming and dispensing units are not turned off at night or plugged into a timer. These types of machines need to remain “on” at all times. This will ensure that appropriate temperatures are maintained in this ready-to-eat food.

4. Management and employees should ensure that any supplied tools for opening the bags of cheese are used per the product directions. These devices need to be washed, rinsed, and sanitized between uses. In some cases these opening tools are only supplied with warming and dispensing unit.

5. Management and employees should verify on a regular basis that the internal temperature of the hot held cheese product is being held at the proper temperature. The internal temperature can be measured by placing the cheese product in a cup with a thermometer to verify the product is maintaining the minimum hot holding temperature of 135 deg. F as required under the California Retail Food Code Section113996 or hot holding temperature as recommended by the manufacturer.

CDPH hopes this information can be shared widely to ensure retail food facilities have current information and are taking appropriate measures to keep our food supply safe. Thank you for your consideration and ongoing collaboration with our Department

 


Botulism in Italy, 1986 to 2015

Eurosurveillance

Eurosurveillance, Volume 22, Issue 24, 15 June 2017

Surveillance and outbreak report                                                                                                                                                                               Anniballi, Auricchio, Fiore, Lonati, Locatelli, Lista, Fillo, Mandarino, and De Medici:                                                                                 Botulism in Italy, 1986 to 2015

“…..From 1986 to 2015, 466 confirmed cases of botulism were recorded in Italy (of 1,257 suspected cases). Of these, 421 were food-borne (the most frequently seen form of botulism due to the consumption of improperly home-canned foods), 36 were infant botulism, which accounts for ca 50% of all these types of cases registered in Europe, six were wound-related and three were due to adult intestinal colonisation. ……”
Clinical signs and symptoms reported by patients with food-borne botulism, Italy, 1986–2015 (n=421)
Clinical sign/symptom Number of cases % of cases
Headache 28 6.6
Double vision 298 70.6
Drooping upper eyelid 43 10.2
Dilation of the pupil 88 20.9
Difficulty in swallowing 304 72.0
Dry mouth 278 65.9
Facial palsy 28 6.6
Respiratory failure 75 17.8
Constipation 209 49.5
Nausea 145 34.4
Vomiting 157 37.2
Abdominal pain 6 1.4
Diarrhoea 40 9.5
Urinary retention 20 4.7
Coma 9 2.1
Death 17 4.0
* Usually, patients presented mild symptomatology, with a clinical picture including diplopia (double vision), dysphagia (difficulty in swallowing), and dry mouth in ca 50% of the cases.
* Respiratory failure was reported in 17.8% (75/421) of patients.
* 16 deaths were recorded, giving a case-fatality rate of 3.8% (16/421), with four of the deaths occurring in elderly patients aged over 80 years who lived alone.

CDC: Summary of Botulism Cases Reported in 2015

CDC

Summary of Botulism Cases Reported in 2015

A total of 199 confirmed and 14 probable cases of botulism were reported to CDC in 2015.

Among confirmed cases, infant botulism accounted for 141 (71%) cases, foodborne botulism for 39 (20%) cases, wound botulism for 15 (8%) cases, and botulism of unknown or other transmission category for 4 (2%) cases (Table 1).

Among probable cases, foodborne botulism accounted for 6 (43%) cases and wound botulism for 8 (57%) cases.

The 141 cases of infant botulism were reported from 33 states and the District of Columbia. The median age of patients was 2.7 months with a range of 0 – 10 months; 70 (50%) were girls. Toxin type A accounted for 60 (43%), toxin type B accounted for 79 (56%), and toxin type Bf accounted for 2 (1%). No deaths were reported.

The 39 cases of confirmed foodborne botulism were reported from 7 states (Figure 1). The median age of patients was 59 years with a range of 9 – 92 years; 25 (64%) were women.

There were 5 outbreaks (events with two or more cases) accounting for 37 confirmed cases. One outbreak was associated with home-canned potatoes in a potato salad served at a church potluck (27 cases),† one was associated with fermented seal flipper (4 cases), and one was associated with beets roasted in aluminum foil and kept at room temperature for several days then made into a soup (2 cases). In addition, there were two outbreaks of two cases each living in the same household or facility in which the foodborne source was unknown (Table 2a).

Toxin type A accounted for 34 (87%), and toxin type E accounted for 5 (13%). One death was reported. The 6 cases of probable foodborne botulism (clinically compatible illness, not laboratory-confirmed, with an epidemiologic link to a suspect food) were reported from 3 states. The median age of patients was 53 years with a range of 23 – 73 years; 3 (50%) were women. No deaths were reported. Seal oil was the suspected food source for 2 of the 6 probable cases (Table 2b). There were 15 cases of confirmed wound botulism reported from 5 states. The median age of patients was 49 years with a range of 12 – 61 years; 2 (13%) were women. Toxin type A accounted for 14 (93%), and toxin type B accounted for 1 (7%). Fourteen (93%) were people who inject drugs (PWID). One death was reported.

The 8 cases of probable wound botulism (clinically compatible case who has no suspected exposure to contaminated food and who has a history in the 2 weeks before illness began of either a fresh wound or injection drug use) were reported from 3 states. The median age of patients was 59 years with a range of 28 – 78 years; 1 (12%) was a woman. All 8 were PWID. No deaths were reported. The 4 confirmed botulism cases of unknown etiology were reported from 3 states. The median age of patients was 47 years with a range of 27 – 71 years; 1 (25%) was a woman. Toxin type A accounted for all 4. No definitive route of transmission was identified for these cases.

Two cases were suspected to be adult intestinal colonization, a rare form of botulism thought to have a similar mechanism as infant botulism. The other two cases did not consume a suspect food, have any wounds, or have any known risk factors for adult intestinal colonization. How these persons were exposed to botulinum toxin is unknown. One patient developed botulism in 2015 and died in 2016 during a prolonged hospitalization.


The Ukraine’s Ministry of Health has said “as of July 18, 2017, 81 cases of botulism were reported in Ukraine, 90 people fell ill, nine of them fatally”.

Daily Express

“…..It is so far unclear how the Ukrainians contracted botulism ….”

 


Ukrainians receive first antitoxin against botulism since 2014

ReliefWeb

“….Over the last months, Ukraine faced an outbreak of botulism – 76 cases recorded since the beginning of the year, 8 of them fatal. Ministry of Health of Ukraine faced a serious challenge fighting the current outbreak, as there are no botulism antitoxins registered in Ukraine since 2014. Moreover, there was no budget funding allocated for procurement of this kind.

International organizations were asked to help resolve the issue. United Nations Development Program reacted and expressed readiness to provide humanitarian response.

The antitoxin, which is produced only by a few manufacturers around the world, was sourced by UNDP within the shortest possible period. High-quality medicine manufactured in Canada arrived to airport in Kyiv today, from where it is being transferred to the specialized warehouse of the Ministry of Health.

Current shipment will allow to form the essential stock, which will be used to immediately cover new cases that might occur. Serums will be urgently provided in case of need…..”


In 2014, 123 cases of botulism were reported by 16 EU/EEA countries, including 91 cases reported as confirmed.

ECDC

Botulism -Europe_ Annual epidemiological report-2016:  Document

Key facts

  • In 2014, 123 cases of botulism were reported by 16 EU/EEA countries, including 91 cases reported as confirmed. Thirteen countries notified zero cases.
  • The notification rate was 0.02 cases per 100 000 population.
  • Romania notified the highest number of cases (N=31) and presented the highest rate (0.15 cases per 100 000 population
  • Methods

Click here for a detailed description of the methods used to produce this annual report

  • In 2014, 29 countries reported data, including 13 countries that reported zero cases.
  • Nine countries reported in accordance with the 2012 EU case definition, 13 countries used the 2008 EU case definition, and the remaining seven countries used other case definitions.
  • Botulism is a mandatorily notifiable disease in all reporting countries.

Epidemiology

In 2014, 123 cases were reported, including 91 confirmed cases, by a total of 16 EU/EEA countries. Thirteen countries had no cases. Italy and Liechtenstein had not reported data for 2014 at the time of the data extraction. The EU/EEA notification rate was 0.02 cases per 100 000 population (Table 1).

Romania (31 confirmed cases), Poland (17) and Hungary (12) were the countries accounting for most of the confirmed cases. Twelve countries reported between one and six confirmed cases each.

Romania (0.15 cases per 100 000), Hungary (0.12 cases per 100 000) and Lithuania (0.10 cases per 100 000) reported the highest rates in 2014 (Table 1).

Threats description for 2014

An outbreak of botulism among injecting drug users in Norway and Scotland started in December 2014. By February 2015, 23 cases of botulism had been reported [1]. The source of the infection was assumed to be contaminated heroin.

Discussion

Figure 3 shows an ascending trend in the rate of botulism notifications in the EU/EEA after July 2012. This observation is based on a small number of cases and does not necessarily represent a real increase in incidence.

The randomly occurring peaks may be explained by small-scale outbreaks due to locally produced food. Botulism cases are often detected as sporadic cases which may belong to household clusters. Case reports and retrospective analyses of cases are useful and complement the mandatory surveillance systems [2,3].

Public health conclusions

While the case definition for surveillance at the EU level focuses on C. botulinum as the etiological agent, sporadic clusters and cases due to type F toxin produced by C. baratii have been reported in recent years [4,5]. These botulism cases due to F toxin type are a cause of concern because the antitoxin is not readily available in Europe, and the commonly used antitoxins may not effectively neutralise toxin F. Preparedness plans may need to consider the timely access to antitoxins in order to cover a broad range of different toxin types, including toxin F [4,5]. In addition, subtyping of botulism neurotoxins is important to monitor the evolution of strains and its implications for public health as exemplified by the recent characterisation of a novel botulism neurotoxin subtype (BoNT/A8) in Germany [6].

References

  1. European Centre for Disease Prevention and Control. Wound botulism in people who inject heroin, Norway and the United Kingdom – 14 February 2015. Stockholm: ECDC; 2015. Available from: http://www.emcdda.europa.eu/system/files/publications/856/09-02-2015-RRA-Botulism-Norway%2C%20United%20Kingdom.pdf .
  2. Ambrožová H, Džupová O, Smíšková D, Roháčová H. Familial occurrence of botulism – A case report. Klinicka Mikrobiologie a Infekcni Lekarstvi. 2014;20(2):40-2.
  3. Lonati D, Flore L, Vecchio S, Giampreti A, Petrolini VM, Anniballi F, et al. Clinical management of foodborne botulism poisoning in emergency setting: An Italian case series. Clinical Toxicology. 2015;53(4):338.
  4. Castor C, Mazuet C, Saint-Leger M, Vygen S, Coutureau J, Durand M, et al. Cluster of two cases of botulism due to Clostridium baratii type F in France, November 2014. Euro Surveill. 2015;20(6):pii=21031.
  5. European Centre for Disease Prevention and Control. Scientific advice on type F botulism. Stockholm: ECDC; 2015. Available from: http://ecdc.europa.eu/en/publications/Publications/botulism-scientific-advice-type-F-botulism.pdf.
  6. Kull S, Schulz KM, Weisemann J, Kirchner S, Schreiber T, Bollenbach A, et al. Isolation and functional characterization of the novel Clostridium botulinum neurotoxin A8 subtype. PLoS One. 2015;10(2):e0116381.

 


The number of botulism cases reported in Ukraine during the past three months has risen to 62

Outbreak News

  • 9 have died.
  • Dried fish, both home prepared and commercially prepared has been linked to most of the botulism cases
  • Officials say some cases have been linked to home prepared stew.
  • There is a lack of  anti-botulinum serum in Ukraine

 


CDC’s Emergency Drugs for US Clinicians and Hospitals

CDC

Our Formulary

The following information is provided as an informational resource for guidance only. It is not intended as a substitute for professional judgment. These highlights and any hyperlinks may not include all the information needed to use each respective drug or biologic safely and effectively. See full prescribing information (package insert) or IND protocol for each respective drug or biologic, which accompany the product when it is delivered to the treating physician and/or pharmacist.

The Drug Service formulary is subject to change based on current public health needs, updates to treatment guidelines, and/or drug availability. For historical reference, we have included products no longer supplied by the Drug Service.

Product & Supplier Indication & Eligibility How Supplied
Anthrax Vaccine Absorbed

(Also known as “AVA”; BioThrax®, Emergent BioSolutions)

For the active immunization for the prevention of disease caused by Bacillus anthracis, in persons 18 through 65 years of age at high risk for exposure

Because the risk for anthrax infection in the general population is low, routine immunization is not recommended

The safety and efficacy of BioThrax® in a post-exposure setting have not been established.

Suspension for injection in 5 mL multidose vials, each containing 10 doses
Artesunate, intravenous

(Supplied to CDC by the Walter Reed Army Institute of Research)

For the treatment of severe malaria in patients who require parenteral (IV) therapy

Patient must meet the eligibility criteria in the IND protocol

110 mg; sterile dry-filled powder with phosphate buffer diluent for reconstitution
Benznidazole

(Benznidazol, Manufactured by LAFEPE)

For the treatment of American trypanosomiasis (Chagas disease)

Patient must meet the eligibility criteria in the IND protocol

100 mg double-scored tablet

12.5 mg dispersible tablet for pediatric use

Botulism Antitoxin Heptavalent (Equine), Types A-G

(Also known as “HBAT”; Manufactured by Cangene Corp. – BAT™)

For the treatment of symptomatic botulism following documented or suspected exposure to botulinum neurotoxin 20 mL or 50 mL single-use glass vial

May be received frozen or thawed

Diethylcarbamazine

(Also known as “DEC”; Supplied to CDC by the World Health Organization; Manufactured by E.I.P.I.C.O.)

For the treatment of certain filarial diseases, including lymphatic filariasis caused by infection with Wuchereria bancrofti, Brugia malayi, or Brugia timori; tropical pulmonary eosinophilia; and loiasis

For prophylactic use in persons determined to be at increased risk for Loa loa infection

Patient must meet the eligibility criteria in the IND protocol

100 mg tablet
Diphtheria Antitoxin (Equine)

(Also known as “DAT”; Manufactured by Instituto Butantan)

For prevention or treatment of actual or suspected cases of diphtheria

Patient must meet the eligibility criteria in the IND protocol

1 mL single-use ampule containing 10,000 units
Eflornithine

(Also known as “DFMO”; Supplied to CDC by the World Health Organization; Manufactured by Sanofi Aventis – Ornidyl®)

For the treatment of second-stage African trypanosomiasis (sleeping sickness) caused by Trypanosoma brucei gambiense, with involvement of the central nervous system 20 g/100 mL hypertonic solution for IV infusion

Must be diluted with Sterile Water for Injection before use

Melarsoprol

(Supplied to CDC by the World Health Organization; Manufactured by Sanofi Aventis – Arsobal®)

For the treatment of second-stage African trypanosomiasis (sleeping sickness), with involvement of the central nervous system

Patient must meet the eligibility criteria in the IND protocol

5 mL glass ampule containing 180 mg/5 mL (36 mg/mL)
Nifurtimox

(Supplied to CDC by the World Health Organization; Manufactured by Bayer – Lampit®)

For the treatment of American trypanosomiasis (Chagas disease)

Patient must meet the eligibility criteria in the IND protocol

120 mg double-scored tablet
Sodium Stibogluconate

(Manufactured by GlaxoSmithKline, UK – Pentostam®)

For the treatment of leishmaniasis

Patient must meet the eligibility criteria in the IND protocol

Solution for injection in 100 mL multidose bottle

100 mg pentavalent antimony (Sb) per mL

Suramin

(Supplied to CDC by the World Health Organization; Manufactured by Bayer – Germanin)

For the treatment of first-stage African trypanosomiasis (sleeping sickness) caused by Trypanosoma brucei rhodesiense, without involvement of the central nervous system

Patient must meet the eligibility criteria in the IND protocol

1 gram of suramin for injection in a 10 mL vial (100 mg/mL solution of suramin sodium)

Must be reconstituted with 10 mL Sterile Water for Injection before use

Vaccinia Vaccine

(Also known as the “Smallpox Vaccine”; Manufactured by Sanofi Aventis – ACAM2000®)

For active immunization against smallpox disease for persons determined to be at high risk for smallpox infection Lyophilized powder reconstituted with diluent (provided)

Contains 100 doses per vial

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Anthrax Vaccine Adsorbed

Anthrax Vaccine Adsorbed (AVA) is indicated for the active immunization for the prevention of disease caused by Bacillus anthracis, in persons 18 through 65 years of age at high risk for exposure. The safety and efficacy of AVA in a post-exposure setting have not been established.

CDC provides anthrax vaccine for laboratory workers conducting research under federally funded projects who require preexposure vaccination based on their occupational risk.

Preexposure vaccination is recommended for laboratorians at risk for repeated exposure to fully virulent B. anthracis spores, such as those who 1) work with high concentrations of spores with potential for aerosol production; 2) handle environmental samples that might contain powders and are associated with anthrax investigations; 3) routinely work with pure cultures of B. anthracis; 4) frequently work in spore-contaminated areas after a bioterrorism attack; or 5) work in other settings where repeated exposures to B. anthracis aerosols may occur. Read more[PDF – 36 pages](https://www.cdc.gov/mmwr/pdf/rr/rr5906.pdf).

More Information for Clinicians

CDC’s Anthrax Vaccination Website

Educational Toolkit for Clinicians (from Department of Defense Anthrax Immunization Program)

Vaccine Information Statement (VIS) for Anthrax Vaccine[PDF – 2 pages](https://www.cdc.gov/vaccines/hcp/vis/vis-statements/anthrax.pdf)

Full Prescribing Information for BioThrax®

How to Request

Anthrax vaccine must be administered by or under the supervision of the physician who registers with CDC.

Contact the CDC Drug Service for more information.

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Artesunate, Intravenous

Artesunate is in the class of medications known as artemesinins, which are derivatives from the “qinghaosu” or sweet wormwood plant (Artemisia annua). Artesunate is not currently licensed by FDA but is made available in the United States under a CDC-sponsored IND protocol for treatment of documented cases of severe malaria(https://www.cdc.gov/malaria/about/index.html) that require parenteral therapy. Read more(https://www.cdc.gov/malaria/diagnosis_treatment/artesunate.html).

More Information for Clinicians

Diagnostic assistance for malaria is available through DPDx.

How to Request

Clinicians who wish to obtain artesunate for severe malaria should contact the CDC Malaria Hotline at 770-488-7788 (M-F, 8am-4:30pm, Eastern time) or, after hours, the CDC Emergency Operations Center (EOC) at 770-488-7100, and request to speak with a CDC Malaria Branch clinician. A Malaria Branch clinician will provide clinical consultation by telephone and, if indicated, authorize the emergency release of artesunate from one of the CDC Quarantine Stations located in major airports around the nation, ensuring delivery to any location in the United States within hours.

Requests for unapproved uses cannot be granted.

For non-emergency questions related to artesunate IV, contact the CDC Drug Service.

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Benznidazole

Benznidazole is a 2-nitroimidazole trypanocidal agent that was introduced in 1971 for the treatment of Trypanosoma cruzi infection—i.e., Chagas disease, also known as American trypanosomiasis(https://www.cdc.gov/parasites/chagas/). Benznidazole is one of two drugs available from CDC for the treatment of Chagas disease (the other is nifurtimox). In the United States, the need to have drugs available for treating Chagas disease has been increasing, largely because of implementation of T. cruzi blood-donor screening in 2007, which has identified chronically infected persons (mainly Latin American immigrants) who might benefit from treatment and has heightened awareness of Chagas disease.

More Information for Clinicians

Evaluation and Treatment of Chagas Disease in the United States: A Systematic Review (JAMA 2007: 298:2171-81)

Screening and Treatment of Chagas Disease in Organ Transplant Recipients in the United States: Recommendations from the Chagas in Transplant Working Group (American Journal of Transplantation, 2011: 672–680)

Diagnostic assistance for American trypanosomiasis is available through DPDx.

How to Request

Contact the CDC Drug Service for more information.

Questions regarding treatment of Chagas disease should be directed to CDC Parasitic Diseases Inquiries (404-718-4745; email chagas@cdc.gov) M-F 7:30am-4pm EST.

For emergencies (for example, acute Chagas disease with severe manifestations, Chagas disease in a newborn, or Chagas disease in an immunocompromised person) outside of regular business hours, call the CDC Emergency Operations Center (770-488-7100) and ask for the person on call for Parasitic Diseases.

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Botulism Antitoxin Heptavalent (Equine), Types A-G

Botulism Antitoxin Heptavalent (HBAT) contains equine-derived antibody to the seven known botulinum toxin types (A-G). HBAT is composed of <2% intact immunoglobulin G (IgG) and ≥90% Fab and F(ab’)2 immunoglobulin fragments. These fragments are created by the enzymatic cleavage and removal of Fc immunoglobulin components in a process sometimes referred to as despeciation. HBAT is supplied on an emergency basis for the treatment of persons thought to be suffering from botulism and works by neutralizing unbound toxin molecules. In 2010, HBAT became the only botulism antitoxin available in the United States for naturally occurring non-infant botulism.

It is available only from CDC because of its limited use and its relatively short expiration date. The antitoxin is stored at CDC Quarantine Stations located in major airports around the nation, ensuring delivery to any location in the United States within hours.

BabyBIG® (botulism immune globulin) remains available for infant botulism through the California Infant Botulism Treatment and Prevention Program.

More Information for Clinicians

Clinical Guidance

How to Request

Clinicians who suspect a diagnosis of botulism in a patient should immediately call their state health department’s 24-hour telephone number(https://www.cdc.gov/mmwr/international/relres.html) to maintain effective botulism surveillance and to facilitate rapid detection of outbreaks. The state health department will contact CDC to arrange for a clinical consultation by telephone and, if indicated, release of botulism antitoxin. State health departments requesting botulism antitoxin should contact the CDC Emergency Operations Center (EOC) at 770-488-7100. Read more(https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5232a8.htm).

For non-emergency questions concerning botulism antitoxin, contact the CDC Drug Service.

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Diethylcarbamazine (DEC)

DEC is an antihelminthic agent used for treatment of lymphatic filariasis (caused by infection with Wuchereria bancrofti, Brugia malayi, or Brugia timori), tropical pulmonary eosinophilia, and loiasis(https://www.cdc.gov/parasites/loiasis/); DEC also has prophylactic benefit for Loa loa infection. DEC has been used worldwide for more than 50 years. In the past, Wyeth-Ayerst Laboratories made DEC available as a licensed drug; in the late 1990s, because of unavailability of a bulk chemical supplier, Wyeth-Ayerst discontinued distribution of DEC in the United States.

More Information for Clinicians

Diagnostic assistance for filarial diseases is available through DPDx.

How to Request

Contact the CDC Drug Service for more information.

Questions regarding treatment of filarial diseases should be directed to CDC Parasitic Diseases Inquiries (404-718-4745; email parasites@cdc.gov) M-F 7:30am-4pm EST.

After-hours emergencies: 1-770-488-7100

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Diphtheria Antitoxin (Equine)

Diphtheria antitoxin (DAT) is used to prevent or treat diphtheria by neutralizing the toxins produced by Corynebacterium diphtheriae. DAT is a sterile, aqueous solution of the refined and concentrated proteins, chiefly globulins, containing antibodies obtained from the serum of horses that have been immunized against diphtheria toxin. DAT is available under an IND protocol sponsored by CDC and is released only for actual or suspected cases of diphtheria(https://www.cdc.gov/diphtheria/about/index.html). The antitoxin is stored at CDC Quarantine Stations located in major airports around the nation, ensuring delivery to any location in the United States within hours.

More Information for Clinicians

CDC’s Vaccine-Related Topics: Diphtheria Antitoxin(https://www.cdc.gov/diphtheria/dat.html)

How to Request

Clinicians who suspect a diagnosis of respiratory diphtheria can obtain DAT by contacting the Emergency Operations Center at 770-488-7100. They will be connected with the diphtheria duty officer, who will provide clinical consultation and, if indicated, initiate the release of diphtheria antitoxin.

For non-emergency questions concerning diphtheria antitoxin, contact the CDC Drug Service.

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Eflornithine

Eflornithine is an antitrypanosomal agent that inhibits the enzyme ornithine decarboxylase. Antitrypanosomal treatment is indicated for all persons diagnosed with African trypanosomiasis (sleeping sickness)(https://www.cdc.gov/parasites/sleepingsickness/); the choice of therapy depends on the infecting subspecies of the parasite and on the stage of the infection. Eflornithine is considered the drug of choice for the treatment of second-stage Trypanosoma brucei gambiense (West African) infection, with involvement of the central nervous system. It is not effective against T. b. rhodesiense (East African) infection (see melarsoprol). Although the manufacturer, Aventis, maintains its US licensure, eflornithine is not commercially available in the United States.

More Information for Clinicians

Human African trypanosomiasis, WHO

Diagnostic assistance for African trypanosomiasis is available through DPDx.

How to Request

Contact the CDC Drug Service for more information.

Questions regarding treatment of African trypanosomiasis should be directed to CDC Parasitic Diseases Inquiries (404-718-4745; email parasites@cdc.gov) M-F 7:30am-4pm EST.

For emergencies outside of regular business hours, call the CDC Emergency Operations Center (770-488-7100) and ask for the person on call for Parasitic Diseases.

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Melarsoprol

Melarsoprol is an organoarsenic compound with trypanocidal effects that has been used outside the United States since 1949. Antitrypanosomal treatment is indicated for all persons diagnosed with African trypanosomiasis (sleeping sickness)(https://www.cdc.gov/parasites/sleepingsickness/); the choice of therapy depends on the infecting subspecies of the parasite and on the stage of the infection. Melarsoprol is used for the treatment of second-stage infection (involving the central nervous system). It is the only available therapy for second-stage Trypanosoma brucei rhodesiense (East African) infection, whereas eflornithine typically is used for second-stage T. b. gambiense (West African) infection.

More Information for Clinicians

Human African trypanosomiasis, WHO

Diagnostic assistance for African trypanosomiasis is available through DPDx.

How to Request

Contact the CDC Drug Service for more information.

Questions regarding treatment of African trypanosomiasis should be directed to CDC Parasitic Diseases Inquiries (404-718-4745; email parasites@cdc.gov) M-F 7:30am-4pm EST.

For emergencies outside of regular business hours, call the CDC Emergency Operations Center (770-488-7100) and ask for the person on call for Parasitic Diseases.

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Nifurtimox

Nifurtimox is a nitrofuran analog that was introduced in 1965 for the treatment of Trypanosoma cruzi infection—i.e., Chagas disease, also known as American trypanosomiasis(https://www.cdc.gov/parasites/chagas/). Nifurtimox is one of two drugs available from CDC for the treatment of Chagas disease (the other is benznidazole). In the United States, the need to have drugs available for treating Chagas disease has been increasing, largely because of implementation of T. cruzi blood-donor screening in 2007, which has identified chronically infected persons (mainly Latin American immigrants) who might benefit from treatment and has heightened awareness of Chagas disease.

More Information for Clinicians

Evaluation and Treatment of Chagas Disease in the United States: A Systematic Review (JAMA 2007: 298:2171-81)

Screening and Treatment of Chagas Disease in Organ Transplant Recipients in the United States: Recommendations from the Chagas in Transplant Working Group (American Journal of Transplantation, 2011: 672–680)

Diagnostic assistance for American trypanosomiasis is available through DPDx.

How to Request

Contact the CDC Drug Service for more information.

Questions regarding treatment of Chagas disease should be directed to CDC Parasitic Diseases Inquiries (404-718-4745; email chagas@cdc.gov) M-F 7:30am-4pm EST.

For emergencies (for example, acute Chagas disease with severe manifestations, Chagas disease in a newborn, or Chagas disease in an immunocompromised person) outside of regular business hours, call the CDC Emergency Operations Center (770-488-7100) and ask for the person on call for Parasitic Diseases.

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Sodium Stibogluconate

Sodium stibogluconate (Pentostam®) is a pentavalent antimony compound used for treatment of leishmaniasis(https://www.cdc.gov/parasites/leishmaniasis). The three main clinical syndromes in humans are visceral, cutaneous, and mucosal leishmaniasis. Pentostam is a well-established antileishmanial agent that has been used in many countries of the world for more than half a century.

More Information for Clinicians

Recommendations for Treating Leishmaniasis with Sodium Stibogluconate (Pentostam) and Review of Pertinent Clinical Studies (Am J Trop Med 1992:46(3):296-306)[PDF, 11 pages]

Diagnostic assistance for leishmaniasis is available through DPDx.

Practical Guide for Laboratory Diagnosis of Leishmaniasis[PDF, 4 pages](https://www.cdc.gov/parasites/leishmaniasis/resources/pdf/cdc_diagnosis_guide_leishmaniasis.pdf)

How to Request

Contact the CDC Drug Service for more information.

Questions regarding treatment of leishmaniasis should be directed to CDC Parasitic Diseases Inquiries (404-718-4745; email parasites@cdc.gov) M-F 7:30am-4pm EST.

After-hours emergencies: 1-770-488-7100

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Suramin

Suramin is a negatively charged, high-molecular-weight sulfated naphthylamine. It was introduced in the 1920s for the treatment of African trypanosomiasis (sleeping sickness)(https://www.cdc.gov/parasites/sleepingsickness/). Suramin generally is considered the drug of choice for first-stage Trypanosoma brucei rhodesiense (East African) infection, without involvement of the central nervous system. Pentamidine typically is used for first-stage T. b. gambiense (West African) infection.

More Information for Clinicians

Human African trypanosomiasis, WHO

Diagnostic assistance for African trypanosomiasis is available through DPDx.

How to Request

Contact the CDC Drug Service for more information.

Questions regarding treatment of African trypanosomiasis should be directed to CDC Parasitic Diseases Inquiries (404-718-4745; email parasites@cdc.gov) M-F 7:30am-4pm EST.

For emergencies outside of regular business hours, call the CDC Emergency Operations Center (770-488-7100) and ask for the person on call for Parasitic Diseases.

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Vaccinia Vaccine, “Smallpox Vaccine”

Smallpox vaccine is made of live vaccinia virus derived from plaque purification cloning of Dryvax® (calf lymph vaccine, New York City Board of Health Strain) and grown in African Green Monkey kidney (Vero) cells and tested to be free of adventitious agents. It contains approximately 2.5 – 12.5 x 105 plaque-forming units per dose.

Smallpox was declared globally eradicated in 1980. In 1982, Wyeth Laboratories, the only active manufacturer of licensed vaccinia vaccine in the United States, discontinued production; and, in 1983, distribution to the civilian population was discontinued. Since January 1982, smallpox vaccination has not been required for international travelers, and International Certificates of Vaccination no longer include smallpox vaccination. ACAM2000® is a new-generation smallpox vaccine that was licensed in 2010 for use as a medical countermeasure held by the Strategic National Stockpile.

CDC recommends vaccinia vaccine for laboratory workers who directly handle a) cultures or b) animals contaminated or infected with nonhighly attenuated vaccinia virus, recombinant vaccinia viruses derived from nonhighly attenuated vaccinia strains, or other orthopoxviruses that infect humans (e.g., monkeypox, cowpox, vaccinia, and variola). Other health-care workers (e.g., physicians and nurses) whose contact with nonhighly attenuated vaccinia viruses is limited to contaminated materials (e.g., dressings) and who adhere to appropriate infection control measures are at lower risk for inadvertent infection than laboratory workers. However, because a theoretical risk for infection exists, vaccination can be offered to this group. Read more[PDF – 930KB](https://www.cdc.gov/mmwr/pdf/rr/rr5010.pdf).

More Information for Clinicians

Full Prescribing Information for ACAM2000®[PDF – 11 pages]

ACAM2000® Medication Guide[PDF – 6 pages]

MMWR Notice to Readers: Newly Licensed Smallpox Vaccine to Replace Old Smallpox Vaccine(https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5708a6.htm)

CDC’s Vaccine-Related Topics: Smallpox Vaccine

How to Request

Smallpox vaccine must be administered by or under the supervision of the physician who registers with CDC.

Ancillary supplies, such as bifurcated needles (for administration) and 1 mL tuberculin syringes with 25 gauge x 5/8″ needles (for reconstitution), are supplied with the vaccine.

Contact the CDC Drug Service for more information.

Requests for unapproved uses cannot be granted.

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Products No Longer Supplied by Drug Service*

Botulinum Toxoid

Pentavalent (ABCDE) botulinum toxoid is a combination of aluminum phosphate-adsorbed toxoid derived from formalin-inactivated types A, B, C, D, and E botulinum toxins, with formaldehyde and thimerosal used as preservatives. Botulinum toxoid was distributed by CDC under an IND protocol for at-risk persons who were actively working or expected to be working with cultures of Clostridium botulinum or the toxins; in 2011, CDC discontinued its program to supply this vaccine. Read more(https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6042a3.htm).

Botulinum Antitoxin Types AB & E

In March 2010, CDC announced the availability of a new heptavalent botulinum antitoxin (HBAT, Cangene Corporation). HBAT replaced the licensed bivalent botulinum antitoxin AB and an investigational monovalent botulinum antitoxin E (BAT-AB and BAT-E, Sanofi Pasteur), becoming the only botulinum antitoxin available in the United States for naturally occurring non-infant botulism. Read more(https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5910a4.htm).

Vaccinia Immune Globulin (VIG)

Vaccinia immune globulin (VIG) is released from the CDC Strategic National Stockpile, if indicated, for the treatment of complications associated with vaccinia vaccination. Clinicians wishing to obtain VIG should contact the Emergency Operations Center (EOC) at 770-488-7100. They will be connected with CDC medical staff who can assist them in the diagnosis and management of patients with suspected complications of vaccinia vaccination.

*this list is not all-inclusive

Use of trade names is for identification only and does not imply endorsement by the U.S. Department of Health and Human Services.


Compounds containing copper and other metal salts were tested in mice, which like humans are vulnerable to the toxin’s blockage of nerve signals to muscles. They penetrated to the site of the neurotoxin’s action, extending the lives of the mice that were given lethal doses.

San Diego Union Tribune

JACS

Metal Ions Effectively Ablate the Action of Botulinum Neurotoxin A

Paul T. Bremer, Sabine Pellett, James Patrick Carolan, William H. Tepp, Lisa M Eubanks, Karen N Allen, Eric A. Johnson,  and Kim D Janda
J. Am. Chem. Soc.,
DOI: 10.1021/jacs.7b01084
Publication Date (Web): May 5, 2017
Copyright © 2017 American Chemical Society

Abstract:  “Botulinum neurotoxin serotype A (BoNT/A) causes a debilitating and potentially fatal illness known as botulism. The toxin is also a known bioterror threat, yet no pharmacological antagonists to counteract its effects has reached clinical approval. Existing strategies to negate BoNT/A intoxication have looked to antibodies, peptides or organic small molecules as potential therapeutics. In this work, a departure from the traditional drug discovery mindset was pursued, in which the enzyme’s susceptibility to metal ions was exploited. A screen of a series of metal salts showed marked inhibitory activity of group 11 and 12 metals against the BoNT/A light chain (LC) protease. Enzyme kinetics revealed that copper (I) and (II) cations displayed noncompetitive inhibition of the LC (Ki ≈ 1 µM), while mercury (II) cations were 10-fold more potent. Crystallographic and mutagenesis studies elucidated a key binding interaction between Cys165 on BoNT/A LC and the inhibitory metals. As potential copper prodrugs, ligand-copper complexes were examined in a cell-based model and were found to prevent BoNT/A cleavage of the endogenous protein substrate, SNAP-25, even at low µM concentrations of complexes. Further investigation of the complexes suggested a bioreductive mechanism causing intracellular release of copper, which directly inhibited the BoNT/A protease. In vivo experiments demonstrated that dithiocarbamate and bis(thiosemicarbazone) copper (II) complexes could delay BoNT/A-mediated lethality in a rodent model, indicating their potential for treating the harmful effects of BoNT/A intoxication. Our studies illustrate that metals can be therapeutically viable enzyme inhibitors; moreover, enzymes that share homology with BoNT LCs may be similarly targeted with metals.”


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