Dear Cheaptrinkets,
There has been quite a lot of research into the negative effects of
the anthrax vaccine, especially in the time since 9/11 when the
military was required to receive it. I did a search for literature
for you and have a list of article citations below that I think will
be of interest to you.
Since you requested all articles available, I have a rather longer
list of citations than I normally give (there are 41 in total). Many
of these are clinical trials or other research - some are editorials
and other non-research based discussions (reviews, tutorials,
lectures). Because of copyright law I am not allowed to give you the
full articles, but you should be able to find most if not all of these
journals in your local university or medical center library. And if
all else fails, the National Library of Medicine has a program called
Loansome Doc that you can use to order articles for $8 apiece
(http://www.nlm.nih.gov/loansomedoc/loansome_home.html). The articles
are arranged in alphabetical order by journal to make it easier to
track them down in the library.
I found these articles in the PubMed MEDLINE database, the primary
literature database for medicine (www.pubmed.gov). I did a search for
"anthrax vaccines/adverse effects"[MeSH]. This search looks in the
subject headings of every article (14 million in total) for articles
about the negative effects of the vaccine. The search found about 53
articles, of which about 10 were either news reports or comments on
other articles. I felt you'd not be interested in those. If you'd
like to see those citations just let me know and I'll add them in.
More information about anthrax and the vaccine is available from
various government and NGO websites. I've found a good index of them
in the MEDLINEplus consumer health website at
http://www.nlm.nih.gov/medlineplus/anthrax.html. MedlinePlus is
organized by the National Library of Medicine, as is PubMed.
Please let me know if/how I can tweak this answer to get you the best
one for your needs.
- Librariankt
1: American journal of health-system pharmacy : AJHP. 2002 Apr 15;59(8):704.
IOM deems anthrax vaccine safe, effective.
[No authors listed]
2: American journal of public health. 2002 May;92(5):715-21.
Comment in:
Am J Public Health. 2002 May;92(5):705-6.
Am J Public Health. 2002 Nov;92(11):1707-8; author reply 1708-9.
The Anthrax Vaccine Program: an analysis of the CDC's recommendations for vaccine
use.
Nass M.
Parkview Hospital, Brunswick, ME, USA.
The anthrax vaccine was never proved to be safe and effective. It is one cause
of Gulf War illnesses, and recent vaccinees report symptoms resembling Gulf War
illnesses. The vaccine's production has been substandard. Without adequate
evaluation, the Food and Drug Administration recently approved (retrospectively)
significant changes made to the vaccine's composition since 1990. The vaccine's
mandatory use for inhalation anthrax is "off-label." A skewed review of the
vaccine literature by the Centers for Disease Control and Prevention (CDC) led
to remunerative collaborative research with the army, involving civilian
volunteers. Despite acknowledging possible fetal harm, the CDC offered the
vaccine to children and pregnant women. New trends could weaken prelicensure
efficacy and safety review of medical products intended for biodefense and avoid
manufacturer liability for their use.
3: Chest. 2002 Aug;122(2):741-5.
Comment in:
Chest. 2003 May;123(5):1769; author reply 1769-70.
Hypersensitivity pneumonitis following anthrax vaccination.
Timmer SJ, Amundson DE, Malone JD.
Pulmonary Division, Department of Internal Medicine, Naval Hospital Pensacola,
Pensacola, FL, USA.
A case of hypersensitivity pneumonitis (HP) following anthrax vaccination is
described. The patient is a 39-year-old, previously healthy man on active duty
in the US Marine Corps, in whom a urticaral skin rash and progressive dyspnea on
exertion developed following subcutaneous anthrax vaccination. A diagnosis of
bronchiolitis obliterans with organizing pneumonia was made from transbronchial
lung biopsy samples after evaluation excluded multiple infectious and collagen
vascular etiologies. This appears to be the first recorded case of HP following
an anthrax vaccination; however, a case report of pulmonary and cutaneous
vasculitis following hepatitis B vaccination has been reported in the literature
and is reviewed.
4: Clinical and experimental rheumatology. 2002 Mar-Apr;20(2):217-20.
Anthrax vaccination and joint related adverse reactions in light of biological
warfare scenarios.
Geier DA, Geier MR.
MedCon, Inc, Silver Spring, Maryland, USA.
OBJECTIVES: The purpose of this analysis was to evaluate anthrax vaccine (AVA)
and joint related adverse reactions based upon analysis of the VAERS database in
light of the current possibility of the use of anthrax as a biological warfare
agent. METHODS: A certified copy of the VAERS database was obtainedfrom the CDC.
In this study, we conducted a retrospective analysis using Microsoft Access for
all joint attributed adverse reactions reported following anthrax vaccination.
The employment of chi-square analysis determined if the elevated incidence rates
of associated adverse reactions in anthrax vaccine recipients were statistically
significant. RESULTS: Our analysis shows a very large and statistically
significant increase in joint symptoms following vaccination with AVA when
compared to our control population consisting of adverse joint reactions
reported following vaccination with hepatitis A vaccine and Td vaccine.
CONCLUSION: We believe that civilian doctors need to become familiar with the
adverse reactions that can be expected to follow the use of AVA. Both civilian
and military doctors need to be vigilant in reporting all such reactions to
VAERS, so that more information can be gathered about AVA. We also believe that
an anthrax vaccine with an improved safety profile is needed if it is to be used
in populations, either military or civilian, that are not under imminent threat
of attack by biological warfare agents. It should also be kept in mind that the
widespread use of anthrax vaccination may cause potential producers of
biological weapons and terrorists to seek to produce anthrax strains that are
not neutralized by the current vaccine.
5: Clinical infectious diseases. 2003 Oct 1;37(7):905-11. Epub 2003 Sep 12.
Serious adverse events among participants in the Centers for Disease Control and
Prevention's Anthrax Vaccine and Antimicrobial Availability Program for persons
at risk for bioterrorism-related inhalational anthrax.
Tierney BC, Martin SW, Franzke LH, Marano N, Reissman DB, Louchart RD, Goff JA,
Rosenstein NE, Sever JL, McNeil MM; Centers for Disease Control and Prevention's
Anthrax Vaccine and Antimicrobial Availability Program.
Epidemiology Program Office, National Center for Infectious Diseases, Centers
for Disease Control and Prevention, Atlanta, Georgia 30333, USA. bgt2@cdc.gov
On 20 December 2001, the Centers for Disease Control and Prevention (CDC)
initiated the Anthrax Vaccine and Antibiotic Availability Program (hereafter,
the "Program") under an investigational new drug application with the US Food
and Drug Administration. This Program provided options for additional preventive
treatment for persons at risk for inhalation anthrax as a result of recent
bioterrorism attacks who had concluded or were concluding a 60-day course of
antimicrobial prophylaxis. Participants were offered an additional 40 days of
antibiotic therapy (with ciprofloxacin, doxycycline, or amoxicillin) or
antibiotic therapy plus 3 doses of anthrax vaccine. By 11 February 2002, a total
of 5420 persons had received standardized education about the Program and 1727
persons (32%) had enrolled. Twelve participants have been identified as having
serious adverse events (SAEs). One SAE, which occurred in a participant with
ciprofloxacin-induced allergic interstitial nephritis, was considered to be
probably associated with treatment received in the Program. No SAEs were
associated with anthrax vaccine. CDC will continue to monitor Program
participants during the next 2 years.
6: Digestive diseases and sciences. 2002 Dec;47(12):2664-8.
Inflammatory causes of gastroparesis: report of five cases.
Pande H, Lacy BE, Crowell MD.
Marvin M. Schuster Center for Digestive and Motility Disorders, The Johns
Hopkins University School of Medicine, Baltimore, Maryland 21224, USA.
7: Duke Law Journal. 2001 Apr;50(6):1835-63.
Friendly fire: the mandatory military anthrax vaccination program.
Katz RD.
8: Emerging infectious diseases. 2002 Jan;8(1):94-6.
Absence of mycoplasma contamination in the anthrax vaccine.
Hart MK, Del Giudice RA, Korch GW Jr.
US Army Research Institute of Infectious Diseases, Fort Detrick, 1425 Porter
Street, Frederick, MD 21702, USA.
9: Experimental and molecular pathology. 2002 Aug;73(1):19-27.
Antibodies to squalene in recipients of anthrax vaccine.
Asa PB, Wilson RB, Garry RF.
Department of Microbiology, Tulane University Medical School, New Orleans,
Louisiana 70112, USA.
We previously reported that antibodies to squalene, an experimental vaccine
adjuvant, are present in persons with symptoms consistent with Gulf War Syndrome
(GWS) (P. B. Asa et al., Exp. Mol. Pathol 68, 196-197, 2000). The United States
Department of Defense initiated the Anthrax Vaccine Immunization Program (AVIP)
in 1997 to immunize 2.4 million military personnel. Because adverse reactions in
vaccinated personnel were similar to symptoms of GWS, we tested AVIP
participants for anti-squalene antibodies (ASA). In a pilot study, 6 of 6
vaccine recipients with GWS-like symptoms were positive for ASA. In a larger
blinded study, only 32% (8/25) of AVIP personnel compared to 15.7% (3/19) of
controls were positive (P > 0.05). Further analysis revealed that ASA were
associated with specific lots of vaccine. The incidence of ASA in personnel in
the blinded study receiving these lots was 47% (8/17) compared to an incidence
of 0% (0/8; P < 0.025) of the AVIP participants receiving other lots of vaccine.
Analysis of additional personnel revealed that in all but one case (19/20; 95%),
ASA were restricted to personnel immunized with lots of vaccine known to contain
squalene. Except for one symptomatic individual, positive clinical findings in
17 ASA-negative personnel were restricted to 4 individuals receiving vaccine
from lots containing squalene. ASA were not present prior to vaccination in
preimmunization sera available from 4 AVIP personnel. Three of these individuals
became ASA positive after vaccination. These results suggest that the production
of ASA in GWS patients is linked to the presence of squalene in certain lots of
anthrax vaccine.
10: Hospital peer review. 2002 Mar;27(3):suppl 1-4.
Bioterrorism watch. Anthrax aftermath: adverse drug reactions, vaccine
controversy undercut CDC extended treatment offer.
Evans G.
11: Journal of the American Academy of Dermatology. 2004 Jan;50(1):136-9.
Oral pemphigus vulgaris after anthrax vaccine administration: association or
coincidence?
Muellenhoff M, Cukrowski T, Morgan M, Dorton D.
Department of Dermatology, Odessa, FL, USA.
Pemphigus vulgaris is an autoimmune blistering disorder of the skin and mucous
membranes. Numerous medications, ultraviolet light, and radiation have all been
implicated in the etiology of the disease. We present a patient with pemphigus
vulgaris whose disease developed after administration of anthrax vaccine. The
histologic and immunofluorescence findings were characteristic of pemphigus
vulgaris. Adverse systemic events associated with the anthrax vaccine consist
primarily of flu-like symptoms. Previous cases of pemphigus vulgaris associated
with anthrax vaccine administration have not been reported. Considering the
recent deliberate outbreaks of anthrax and continued threats of bioterrorism,
the potential exists for widespread administration of the anthrax vaccine.
Accordingly, continued observation and documentation of true adverse events is
needed.
12: Journal of the Association for Academic Minority Physicians. 2002
Jan;13(1):19-22.
Vaccines for adults in an age of terrorism.
Simberkoff MS.
Infectious Diseases Section and Executive Office, VA New York Harbor Healthcare
System, Department of Medicine, NYU School of Medicine, USA.
Vaccines are an effective, safe, and relatively inexpensive means of preventing
infection; thus, they are important tools for fighting biological terrorism. Two
diseases, anthrax and smallpox, for which vaccines are not available to the
general public are discussed. Three other vaccines--tetanus toxoid, influenza
vaccine, and hepatitis B vaccine--generally recommended for adults, may be in
short supply as a result of recent acts of terrorism.
13: Journal of emergency medicine. 2003 Oct;25(3):271-6.
Lymphocytic vasculitis associated with the anthrax vaccine: case report and
review of anthrax vaccination.
Muniz AE.
Department of Emergency Medicine and Pediatrics, Medical College of Virginia,
401 N. 12th Street, Richmond, VA 23298-0401, USA.
Anthrax is caused by the spore-forming bacteria Bacillus anthracis. It occurs
naturally, but recently has been manufactured as a biological warfare agent.
This makes prophylaxis for anthrax an urgent concern and efforts are ongoing for
the production of an efficient and safe vaccine. Side effects to the current
anthrax vaccine are usually minor and mainly consist of local skin reactions.
Occasionally an unusual complication may occur; a case of a patient with
lymphocytic vasculitis temporally associated with the anthrax vaccine is
reported.
14: Journal of family practice. 2003 Jan;52(1 Suppl):S56-61.
Vaccines and bioterrorism: smallpox and anthrax.
Kimmel SR, Mahoney MC, Zimmerman RK.
Department of Family Medicine, Medical College of Ohio, Toledo, OH 43614, USA.
skimmel@mco.edu
Because of the success of vaccination and the ring strategy in eradicating
smallpox from the world, smallpox vaccine has not been recommended for the
United States civilian populations for decades. Given the low but possible
threat of bioterrorism, smallpox vaccination is now recommended for those teams
investigating potential smallpox cases and for selected personnel of acute-care
hospitals who would be needed to care for victims in the event of a terrorist
attack. Treatment and post-exposure prophylaxis for anthrax are ciprofloxacin or
doxycycline. Anthrax vaccine alone is not effective for post-exposure prevention
of anthrax; vaccination is accompanied by 60 days of antibiotic therapy. In
addition to military use, anthrax vaccine is recommended for pre-exposure use in
those persons whose work involves repeated exposure to Bacillus anthracis
spores.
15: Journal of occupational and environmental medicine. 2003 Mar;45(3):222-33.
Analysis of adverse events after anthrax immunization in US Army medical
personnel.
Wasserman GM, Grabenstein JD, Pittman PR, Rubertone MV, Gibbs PP, Wang LZ,
Golder LG.
Preventive Medicine Department, Tripler Army Medical Center, Honolulu, Hawaii,
USA. glenn.wasserman@amedd.army.mil
A broad range of health effects in a cohort of 601 health care personnel,
immunized with anthrax vaccine adsorbed (AVA) as a military occupational health
requirement, were assessed to evaluate adverse events both qualitatively and
quantitatively. Active surveillance showed that localized reactions were common
and occurred more often in women than men. Five patients were reported to the
Vaccine Adverse Event Reporting System, but only one event could be definitively
attributed to immunization, a large localized reaction. Two separate cohort
studies, one using nested data from a standardized health risk appraisal
instrument and the other comparing rates of outpatient visits and
hospitalizations, did not reveal significant differences between AVA-immunized
and unimmunized individuals. Our findings suggest that AVA is relatively
reactogenic but do not indicate serious adverse health effects due to
immunization.
16: Journal of the Royal Army Medical Corps. 2000 Oct;146(3):191-5.
Adverse reactions to anthrax immunisation in a military field hospital.
Hayes SC, World MJ.
33 Field Hospital Fort Blockhouse, Gosport, Hants, PO12 2AB.
OBJECTIVE: To determine the outcome of anthrax immunisation. METHODS: Adverse
reactions (occurrence, nature, severity and incapacity) and immune responses to
a voluntary programme of anthrax immunisation at 0, 3, 6, and 24 weeks were
monitored by questionnaire and voluntary blood sampling in 129 members,
including 24 immunised 7 years previously (immunes), of a military field
hospital alerted for possible deployment. RESULTS: Follow-up was complete in
85%. Ninety-eight (76%) received the first anthrax immunisation. Uptake was
greater (p = 0.015) in immunes. Initial prevalence of adverse reaction was 63%.
Subsequent uptake and adverse reaction dwindled significantly (p < 0.001). Only
28 (22%) were immunised at 24 weeks. Proportions reporting adverse reactions
following the initial immunisation were greater in immunes (p = 0.046) and
officers (p = 0.02). There was no significant (p = 0.36) correlation between
uptake of immunisation and prevalence of adverse reaction. Antecedent adverse
reaction did not reduce the proportion of participants accepting immunisation
subsequently. The nature of adverse reactions (47% local, 24% systemic and 27%
both) and severity were the same throughout. Forty-five percent of adverse
reactions caused incapacity. Seventy-four percent of these had pain in the
injected arm (+/- systemic symptoms) which prevented lifting or driving for 48
hours in 63%. Immune responses were greater in immunes. CONCLUSIONS: It was
concluded that anthrax immunisation results in a higher than expected prevalence
of adverse reaction with initial incapacity of military significance affecting
18%. Greater immune responses may increase adverse reaction but this does not
affect acceptance of anthrax immunisation. Poor completion rates necessitate
development of a new anthrax immunisation strategy.
17: Journal of toxicology. Clinical toxicology. 2001;39(1):85-100.
Use of anthrax vaccine in the United States: recommendations of the Advisory
Committee on Immunization Practices.
[No authors listed]
These recommendations concern the use of aluminum hydroxide adsorbed cell-free
anthrax vaccine (Anthrax Vaccine Adsorbed [AVA], BioPort Corporation, Lansing,
MI) in the United States for protection against disease caused by Bacillus
anthracis. In addition, information is included regarding the use of
chemoprophylaxis against B. anthracis.
18: Journal of toxicology. Clinical toxicology. 2001;39(1):81-4.
Delayed life-threatening reaction to anthrax vaccine.
Swanson-Biearman B, Krenzelok EP.
Pittsburgh Poison Center, Children's Hospital of Pittsburgh, Pennsylvania 15213,
USA.
BACKGROUND: Anthrax is an acute infectious disease caused by the spore-forming
bacterium Bacillus anthracis. Due to the current world threat of unpredictable
biological terrorism, the Department of Defense has mandated the systematic
vaccination of all US military personnel against this warfare agent. Many may
experience al mild flu-like illness and soreness at the injection site, but
systemic reactions are rare. CASE REPORT: We report a delayed and potentially
serious life-threatening adverse reaction to anthrax vaccine. A previously
healthy 34-year-old male was transported to the emergency department with
dyspnea, diaphoresis, pallor, and urticarial wheals on his face, arms, and torso
after the administration of the third dose of anthrax vaccine. All symptoms
resolved after pharmacological intervention and the patient was discharged.
Pharmaco-epidemiological data indicate that 30% of anthrax vaccine recipients
experience mild local reactions. With large numbers of military personnel being
vaccinated, emergency physicians may encounter more vaccine-related adverse
reactions.
19: JAMA : the journal of the American Medical Association. 2002 Mar
27;287(12):1556-60.
Relationship between prepregnancy anthrax vaccination and pregnancy and birth
outcomes among US Army women.
Wiesen AR, Littell CT.
Department of Preventive Medicine, Madigan Army Medical Center, Tacoma, WA
98431, USA. andrew.wiesen@amedd.army.mil
CONTEXT: Substantial concern surrounds the potential health effects of the
anthrax vaccine, particularly the potential adverse effects on reproductive
processes. OBJECTIVE: To determine whether receipt of anthrax vaccination by
reproductive-aged women has an effect on pregnancy rates. DESIGN, SETTING, AND
PATIENTS: Cohort study, based on information from a computer database, of women
aged 17 to 44 years who were stationed at Fort Stewart, Ga, or Hunter Army
Airfield, Ga, from January 1999 through March 2000. MAIN OUTCOME MEASURES:
Pregnancy and birth rates and adverse birth outcomes. RESULTS: Of a total of
4092 women, 3136 received at least 1 dose of the anthrax vaccine. There was a
total of 513 pregnancies, with 385 following at least 1 dose of anthrax vaccine.
The pregnancy rate ratio (before and after adjustment for marital status, race,
and age) comparing vaccinated with unvaccinated women was 0.94 (95% confidence
interval [CI], 0.8-1.2; P =.60). There were 353 live births and 25 pregnancies
lost to follow-up. The birth odds ratio after anthrax vaccination (before and
after adjustment for marital status and age) was 0.9 (95% CI, 0.5-1.4; P =.55).
After adjusting for age, the odds ratio for adverse birth outcome after
receiving at least 1 dose of anthrax vaccination was 0.9 (95% CI, 0.4-2.4; P
=.88). However, this study did not have sufficient power to detect adverse birth
outcomes. CONCLUSION: Anthrax vaccination had no effect on pregnancy and birth
rates or adverse birth outcomes.
20: JAMA : the journal of the American Medical Association. 2002 Mar
6;287(9):1107.
From the Centers for Disease Control. Status of US Department of Defense
preliminary evaluation of the association of anthrax vaccination and congenital
anomalies.
[No authors listed]
21: The lancet oncology. 2002 Jun;3(6):331.
Vaccines against dangerous infections and cancer.
Nersesyan AK.
Laboratory of Carcinogenesis, Cancer Research Centre, Yerevan State University,
1 Alex Manoukian Street, Yerevan 25, Armenia.
22: Military medicine. 2002 Mar;167(3):205-10.
Ambulatory medical visits among anthrax-vaccinated and unvaccinated personnel
after return from southwest Asia.
Rehme PA, Williams R, Grabenstein J.
Air National Guard, Office of the Air Surgeon, 3500 Fetchet Avenue, Andrews Air
Force Base, MD 20762, USA.
The Department of Defense launched a mandatory anthrax immunization program for
military personnel in December 1997. This program has been criticized for many
reasons, including concern over side effects. This study was designed to give a
quick answer to the question of whether vaccinated persons who deployed to
southwest Asia were more likely to seek medical care upon their return than
their unvaccinated counterparts. The results demonstrated that there was no
greater risk for vaccinated persons to have a diagnosis recorded in the
Ambulatory Data System (0.96 RR) than unvaccinated persons. In addition, there
was no significant increased risk for a recorded diagnosis in any 1 of the 17
International Classification of Diseases, Ninth Revision, categories or for 16
specific adverse health conditions.
23: Military medicine. 2002 Jan;167(1):74-5.
Delayed-type hypersensitivity reaction to anthrax vaccine.
Greidanus TG, Honl BA.
Evans Army Community Hospital, Fort Carson, CO, USA.
The Anthrax Vaccine Immunization Program is a Department of Defense initiative
to protect military personnel against the threat of anthrax. Surveillance for
adverse events associated with anthrax vaccination has shown that mild local
reactions are not uncommon while systemic reactions are extremely rare. We
present a case of 26-year-old male with delayed-type hypersensitivity after two
doses of anthrax vaccine.
24: Military medicine. 2001 Dec;166(12 Suppl):36-40.
The psychosocial aspect of the Anthrax vaccine: "the Dover experience".
Holmstedt-Mark BJ, Smolinsky FT, Bradshaw D.
436th ADOS, 300 Tuskeegee Blvd/SGPF, Dover Air Force Base, DE 19902, USA.
barbara.holmstedt-mark@dover.af.mil
25: MMWR. Recommendations and reports. 2000 Dec 15;49(RR-15):1-20.
Use of anthrax vaccine in the United States.
Advisory Committee on Immunization Practices.
These recommendations concern the use of aluminum hydroxide adsorbed cell-free
anthrax vaccine (Anthrax Vaccine Adsorbed [AVA], BioPort Corporation, Lansing,
MI) in the United States for protection against disease caused by Bacillus
anthracis. In addition, information is included regarding the use of
chemoprophylaxis against B. anthracis.
26: Nursing times. 2001 Nov 1-7;97(44):10-1.
Anthrax. When immunity may not be safe.
Munro R.
robert.munro@emap.com
27: Ophthalmology. 2002 Jan;109(1):99-104.
Optic neuritis after anthrax vaccination.
Kerrison JB, Lounsbury D, Thirkill CE, Lane RG, Schatz MP, Engler RM.
Department of Ophthalmology, Wilford Hall Medical Center, 2200 Bergquist Drive,
Lackland AFB, Texas 78236, USA.
OBJECTIVE: To report the occurrence of optic neuritis after anthrax vaccination
in two patients. DESIGN: Observational case reports, review of literature.
METHODS: Description of clinical history, examination, neuroimaging, and further
studies in two patients experiencing optic neuritis in temporal association with
anthrax vaccination. MAIN OUTCOME MEASURES: Visual acuity, visual fields.
RESULTS: Two patients, 39 and 23 years of age, were seen with acute optic
neuritis 1 month and 2 weeks, respectively, after anthrax booster vaccination
and successfully treated with intravenous methylprednisolone. The first patient
had a typical presentation and course of unilateral retrobulbar optic neuritis
with excellent visual recovery. The second patient had a bilateral anterior
optic neuritis and has required chronic immunosuppression to maintain his
vision. Retinal and optic nerve autoantibodies were present in the second
patient. No cross-reactive epitopes between anthrax vaccine and retina/optic
nerve were identified. CONCLUSION: Optic neuritis is a potential adverse
reaction of anthrax vaccination.
28: Pharmacoepidemiology and drug safety. 2002 Apr-May;11(3):189-202.
Safety of anthrax vaccine: a review by the Anthrax Vaccine Expert Committee
(AVEC) of adverse events reported to the Vaccine Adverse Event Reporting System
(VAERS).
Sever JL, Brenner AI, Gale AD, Lyle JM, Moulton LH, West DJ; Anthrax Vaccine
Export Committee.
Departments of Pediatrics, Obstetrics and Gynecology, Microbiology and
Immunology, Children's National Medical Center, George Washington University,
School of Medicine, 111 Michigan Avenue, N.W., Washington, DC 20010-2970, USA.
jsever@cnmc.org
PURPOSE: To assess the safety of a licensed anthrax vaccine given to nearly
400,000 US military personnel, reports of adverse events (AEs) submitted to the
Vaccine Adverse Event Reporting System (VAERS) were reviewed and evaluated
medically. METHODS: The Anthrax Vaccine Expert Committee (AVEC), a civilian
panel of private-sector physicians and other scientists, reviewed 602 VAERS
reports using a Delphic approach (structured expert consensus) to assess the
causal relationship between vaccination and the reported AEs and sought to
identify unexpected patterns in the occurrence of medically important events.
Reports were entered into a database and used to profile AEs with respect to
person, type/location, relative frequency, severity/impact, concomitant illness
or receipt of other drugs or vaccines, and vaccine lot. RESULTS: Nearly half the
reports noted a local injection-site AE, with more than one-third of these
involving a moderate to large degree of inflammation. Six events qualified as
serious AEs (SAEs), and all were judged to be certain consequences of
vaccination. Three-quarters of the reports cited a systemic AE (most common:
flu-like symptoms, malaise, rash, arthralgia, headache), but only six individual
medically important events were judged possibly or probably due to vaccine
(aggravation of spondyloarthropathy (2), anaphylactoid reaction, arthritis (2),
bronchiolitis obliterans organizing pneumonia). CONCLUSIONS: Since some cases of
local inflammation involved distal paresthesia, AVEC recommends giving
subcutaneous injections of AVA over the inferior deltoid instead of the triceps
to avoid compression injury to the ulnar nerve. At this time, ongoing evaluation
of VAERS reports does not suggest a high frequency or unusual pattern of serious
or other medically important AEs.
29: Pharmacoepidemiology and drug safety. 2002 Apr-May;11(3):185-7;
discussion 203-4.
Comment in:
Pharmacoepidemiol Drug Saf. 2002 Oct-Nov;11(7):615-6.
Anthrax vaccine and causality assessment from individual case reports.
Halsey NA.
30: Psychological reports. 2002 Aug;91(1):187-91.
Comments on the Institute of Medicine's 2002 report on the safety of anthrax
vaccine.
Schumm WR, Webb FJ, Jurich AP, Bollman SR.
School of Family Studies and Human Services, Kansas State University, Manhattan
66506-1403, USA. Schumm@Humec.ksu.edu
In April 2002, the prestigious Institute of Medicine of the National Academy of
Sciences issued a final report on the safety and effectiveness of the anthrax
vaccine currently in use by the United States military. It concluded that the
present vaccine was completely safe and effective, but ignored evidence of
several recent research studies from three different nations that have
implicated vaccines, often including anthrax vaccine, in the epidemiology of
Gulf War illnesses. Omissions and limitations of that report are discussed.
31: Public health reports. 2002 Nov-Dec;117(6):513-20.
Anthrax: the precautionary principle goes postal.
Ozonoff D.
Department of Environmental Health, Boston University School of Public Health,
MA 02118, USA. dozonoff@bu.edu
32: Science. 2002 Jul 12;297(5579):201-2.
Microbiology. A binding contract for anthrax.
Bull JJ, Parrish CR.
Section of Integrative Biology and Institute for Cellular and Molecular Biology,
University of Texas, Austin, TX 78712, USA. bull@bull.biosci.utexas.edu
33: Vaccine. 2003 Oct 1;21(27-30):4399-409.
Using a structured medical note for determining the safety profile of anthrax
vaccine for US soldiers in Korea.
Hoffman K, Costello C, Menich M, Grabenstein JD, Engler RJ.
Military and Veterans Health Coordinating Board, 20420-0002, Washington, DC
20420-0002, USA. khoffman100@comcast.net
Selected military personnel are immunized with an FDA-licensed anthrax vaccine
unless there are clinical contraindications. The objective of this analysis is
to capture the experience of soldiers receiving anthrax vaccine to assist in
better patient-provider communication and clarify the safety profile of the
vaccine in this population as a quality-assurance initiative. Between August
1998 and July 1999, 2824 soldiers immunized against anthrax at one military
clinic completed a structured medical note that was reviewed by a clinician.
Female gender, prior vaccine-associated adverse events, and medication use were
significantly related to higher reports of adverse events. All reported
immediate consequences resolved.
34: Vaccine. 2003 Apr 2;21(15):1620-8.
Comprehensive systematic surveillance for adverse effects of anthrax vaccine
adsorbed, US Armed Forces, 1998-2000.
Lange JL, Lesikar SE, Rubertone MV, Brundage JF.
Army Medical Surveillance Activity, US Army Center for Health Promotion and
Preventive Medicine, Building T-20, Room 213 (Attn: MCHB-TS-EDM), 6900 Georgia
Avenue, NW, Washington, DC 20307-5001, USA.
Routine vaccinations of US military personnel with Anthrax Vaccine Adsorbed
began in 1998. To systematically identify clinical diagnoses reported more
frequently after vaccination than before, all military personnel were
retrospectively assigned to pre- or post-vaccination cohorts. Cohort assignments
were based on vaccination statuses each day of the 3-year surveillance period.
For each cohort, rates of hospitalizations and ambulatory visits for 843
specific diagnoses were calculated using data in a public health surveillance
system. Compared to the pre-vaccination cohort, the post-vaccination cohort had
statistically higher rates of hospitalizations for 17 diagnoses, of ambulatory
visits for 34 diagnoses, and in both clinical settings for one diagnosis
(malaria). After accounting for systematic differences in coding/reporting and
residual confounding, the number and nature of clinical diagnoses more frequent
after anthrax vaccination than before were consistent with expectations due to
random variation. This surveillance suggests that Anthrax Vaccine Adsorbed has
few, if any, clinically significant adverse effects.
35: Vaccine. 2003 Mar 28;21(13-14):1348-54.
Adverse medical events in British service personnel following anthrax
vaccination.
Enstone JE, Wale MC, Nguyen-Van-Tam JS, Pearson JC.
Division of Public Health Sciences, University of Nottingham Medical School,
Queen's Medical Centre, UK.
The safety of the UK anthrax vaccine in British service personnel was evaluated
by a retrospective cohort study of randomly selected personnel from five Royal
Air Force bases by investigating adverse medical events and consultation rates
for a period before and after vaccination. Vaccination acceptance rate varied
from 27 to 89% (P=0.0001). In the vaccinated cohort 11.1% (n=368) reported
side-effects. The number of consultations in the year prior to vaccination
(P=0.04) and RAF base (P=0.0085) were associated with side-effects. Only the RAF
base remained a statistically significant factor (P=0.007) after adjusting for
other factors. The anthrax vaccine resulted in mild side-effects in 11%, and no
serious side-effects were observed. Acceptors of vaccine did not have
significantly more medical consultations following vaccination than their
unvaccinated counterparts.
36: Vaccine. 2002 May 31;20 Suppl 3:S48-50.
Aluminum-containing vaccine associated adverse events: role of route of
administration and gender.
Pittman PR.
phillip.pittman@det.amedd.army.mil
Anthrax vaccine, adsorbed (AVA) is a vaccine containing aluminum hydroxide that
is administered as six subcutaneous (s.q.) doses over 18 months. It is the only
aluminum hydroxide licensed for s.q. administration. To optimize the vaccination
schedule and route of administration, a prospective pilot study comparing the
use of fewer doses administered intramuscularly (i.m.) as well as s.q. with the
licensed schedule and route was performed. Data from that study on injection
site reactions were extracted for this report. Erythema and induration occurred
more commonly when the vaccine was administered s.q. compared to i.m. (P <
0.0001, P = 0.002, respectively). S.q. nodules were found only among the s.q.
group (P < 0.0001). Erythema, induration and s.q. nodules were more common in
women compared with men (P < 0.001) after the first s.q. dose of AVA dose.
Reaction rates decreased when the interval between the first two doses of AVA
was increased from 2 to 4 weeks.
37: Vaccine. 2002 May 22;20(17-18):2369-74.
Monitoring anthrax vaccine safety in US military service members on active duty:
surveillance of 1998 hospitalizations in temporal association with anthrax
immunization.
Sato PA, Reed RJ, Smith TC, Wang L.
Department of Defense Center for Deployment Health Research, Naval Health
Research Center, San Diego, CA 92186-5122, USA.
We compared 1998 hospitalizations in active-duty US military personnel for
possible temporal association with anthrax immunization. Immunization,
demographic, and hospitalization data were analyzed using Cox proportional
hazards modeling for hospitalization within 42 days of vaccination. Discharge
diagnoses were aggregated into 14 International Classification of Disease, Ninth
Revision, Clinical Modification (ICD-9-CM) categories. Approximately 11% of
subjects received one or more doses of vaccine during 1998; those immunized were
more likely to be younger and male. Lower hospitalization rates were observed
across doses and diagnostic categories among the immunized. Adjusted risk ratios
for hospitalization by diagnostic category suggest that immunized service
members were at equal or lesser risk for hospitalization than the non-immunized.
38: Vaccine. 2002 May 15;20(16):2107-15.
Antibody response to a delayed booster dose of anthrax vaccine and botulinum
toxoid.
Pittman PR, Hack D, Mangiafico J, Gibbs P, McKee KT Jr, Friedlander AM, Sjogren
MH.
United States Army Medical Research Institute of Infectious Diseases, Fort
Detrick, MD, USA. philip.pitmann@det.amedd.army.mil
We evaluated the prevalence and concentration of serum antibodies 18-24 months
after primary inoculation with anthrax and botulinum vaccines, and assessed the
reactogenicity and immunogenicity of a significantly delayed booster dose of
these vaccines. Five hundred and eight male active-duty military personnel
received one, two or three inoculations with anthrax vaccine and/or botulinum
toxoid in 1990/1991 in preparation for Operations Desert Shield/Desert Storm.
Subjects were vaccinated with the licensed anthrax vaccine, adsorbed (AVA) and
pentavalent (ABCDE) botulinum toxoid (PBT) BB-IND 3723. Anthrax protective
antigen (PA) IgG antibody was measured in serum using an immunocapture
enzyme-linked immunosorbent assay (ELISA). A mouse neutralization test was used
to determine the titer of Clostridium botulinum type A antitoxin in serum
samples. The prevalence of anti-PA IgG was 30% in individuals 18-24 months after
priming with one, two or three doses of AVA. After boosting, 99% of volunteers
had detectable anti-PA IgG; only two individuals failed to respond. The
prevalence of antibodies against botulinum toxin type A was 28% 18-24 months
after initial priming. Following boosting, 99% of volunteers had serum titers
>0.02IU/ml, and 97% responded with titers > or =0.25IU/ml.Systemic reactions to
booster vaccinations could not be specifically ascribed to one or the other
vaccine, but were generally mild and of brief duration. Forty-five percent of
volunteers reported one or more systemic reactions over the course of 7 days.
Injection site reactions of any kind occurred in 25% of AVA recipients and in
16% of PBT recipients; persistence of local reactions beyond 7 days was
infrequent.While the kinetics and durability of immune responses must be
studied, these findings suggest that booster doses of anthrax vaccine and
botulinum toxoid sufficient to stimulate a robust anamnestic response may be
given at times distant from receipt of the primary inoculations.
39: Vaccine. 2002 Jan 31;20(9-10):1412-20.
Anthrax vaccine: immunogenicity and safety of a dose-reduction, route-change
comparison study in humans.
Pittman PR, Kim-Ahn G, Pifat DY, Coonan K, Gibbs P, Little S, Pace-Templeton JG,
Myers R, Parker GW, Friedlander AM.
Division of Medicine, United States Army Medical Research Institute of
Infectious Diseases (USAMRIID), Fort Detrick, MD 21702-5011, USA.
phillip.pittman@det.amedd.army.mil
Anthrax vaccine adsorbed (AVA), an effective countermeasure against anthrax, is
administered as six subcutaneous (SQ) doses over 18 months. To optimize the
vaccination schedule and route of administration, we performed a prospective
pilot study comparing the use of fewer AVA doses administered intramuscularly
(IM) or SQ with the current schedule and route. We enrolled 173 volunteers,
randomized to seven groups, who were given AVA once IM or SQ; two doses, 2 or 4
weeks apart, IM or SQ; or six doses at 0, 2, 4 weeks and 6, 12, and 18 months
(control group, licensed schedule and route). IM administration of AVA was
associated with fewer injection site reactions than SQ administration. Following
the first SQ dose of AVA, compared to males, females had a significantly higher
rate of injection site reactions such as erythema, induration and subcutaneous
nodules (P<0.001). Reaction rates decreased with a longer dose interval between
the first two doses. The peak anti-PA IgG antibody response of subjects given
two doses of AVA 4 weeks apart IM or SQ was comparable to that seen among
subjects who received three doses of AVA at 2-week intervals. The IM route of
administering this aluminum hydroxide adsorbed vaccine is safe and has
comparable peak anti-PA IgG antibody levels when two doses are administered 4
weeks apart compared to the licensed initial dose schedule of three doses
administered 2 weeks apart. A large pivotal study is being planned by the
Centers for Disease Control and Prevention to confirm these results.
40: Vaccine. 2001 Dec 12;20(5-6):972-8.
Anthrax vaccine: short-term safety experience in humans.
Pittman PR, Gibbs PH, Cannon TL, Friedlander AM.
Division of Medicine, US Army Medical Research Institute of Infectious Diseases,
1425 Porter Street, Fort Detrick, Frederick, MD 21702-5011, USA.
phillip.pittman@det.amedd.army.mil
Bacillus anthracis is the major terrorist and biological warfare agent of
concern to civilian and military medical planners. The licensed anthrax vaccine,
adsorbed (AVA) is believed to be an effective prophylactic medical
countermeasure against this threat. Our objective in this report was to expand
the safety database for this vaccine by assessing data on self-reported,
short-term safety of AVA during more than 25 years of use, measured by local and
systemic adverse events temporally associated with the administration of AVA. A
minority of AVA recipients reported systemic and injection site reactions.
Females reported a higher incidence of injection site and systemic adverse
events than males. Data show a difference in incidence of local reactions
between lots. A prospective, randomized, placebo-controlled study to actively
examine reactogenicity is needed to more completely define the extent and nature
of reactions associated with receipt of AVA in humans as well as to confirm the
gender lot differences in local reaction rates.
41: Vaccine. 2001 Jul 20;19(30):4214-8.
Detection of anthrax vaccine virulence factors by polymerase chain reaction.
Fasanella A, Losito S, Trotta T, Adone R, Massa S, Ciuchini F, Chiocco D.
Istituto Zooprofilattico Sperimentale della Puglia e della Basilicata, Via
Manfredonia 20, 71100, Foggia, Italy. izsfoggia@isnet.it
In Italy, an attenuated Bacillus anthracis strain, named 'Carbosap', is used for
immunization against ovine and bovine anthrax. Analysis on 'Carbosap', Sterne
vaccine strain F34 and Pasteur vaccine strain SS104, were performed using
primers specific for the sequences, encoding the toxic factors, located on
plasmids pXO1 and pXO2 and primers specific for the chromosome. The results
obtained from polymerase chain reaction (PCR) assay revealed the presence of
both plasmids pXO1 and pXO2 in 'Carbosap' strain. This study showed that the
'Carbosap' vaccine strain has a different plasmid pattern in comparison to
Pasteur vaccine strain SS104 and Sterne vaccine strain F34. |
