Transcript C. sordellii - York College of Pennsylvania

Investigation of Clostridium sordellii Blood
Infection Associated With Medicinal Abortions
Christine Humphrey
York College of Pennsylvania, Department of Biological Sciences
http://www.health-insurance.org/rare-deadly-diseases
Project Summary
http://www.farrin.com/drugs-and-products/drug-recalls.php
Review of Literature
40 BALB/c mice at the same
gestation period
The drugs used in a medicinal
abortion have a modulatory effect on
the immune system. There is also a
blood infection with Clostridium
sordellii associated with the procedure.
While rare, the infection is very
dangerous because the side effects of
the procedure mask the symptoms of
the infection, and delay diagnosis.
These rare cases all ended tragically.
This project will investigate the
effect of misoprostol on the immune
system, the reaction of the infection
while in the presence of misoprostol,
and the average time of death of an
infected subject. An animal model will
be used because of the complexity of
the immune system.
Introduction
Within the population, 10% of
women naturally have C. sordellii as a
part of their natural vaginal flora (Meich
2005). This is an anaerobic, gram
positive bacteria who’s infections are
associated with gas gangrene, and
Toxic Shock Syndrome, and unaffected
by some of the most powerful
antibiotics in use (McGregor 1989).
Several cases in the US and
Canada have shown previously healthy
women undergoing medicinal abortions
and ending up in the hospital with a
fatal C. sordellii sepsis (McGregor
1989).
Medicinal abortions are a two part
procedure that can be done in the
privacy of one’s home. Mifeprex, is
composed of Mifepristone (RU486) and
Misoprostol (Prostaglandin E). RU486
blocks the cytokine synthesis pathway
and
the body
becomes
more
susceptible to infection (Miech 2005).
This raises the question of the
effects of the second portion of the
medicine. Prostaglandin E is used for
induction of uterine contraction in
natural childbirths (El-Rafaey 1995).
There is very little knowledge of the
hormone’s effect on infections, or the
immune system.
Expected Results
Research Design
Group 1:
Misoprostol
Treatment
Group 2:
C. sordellii
Filtrate
Treatment
Group 3:
Misoprostol and
C. sordellii
Filtrate
10 Mice
10 Mice
10 Mice
-1ug/kg of
-Oral Placebo
-1ug/kg of
misoprostol
-Intraperitoneal
misoprostol
-Intraperitoneal
injection of 1:50
-Intraperitoneal
injection of 1:50
dilution of filtrate
injection of .5M
dilution of filtrate
and .5M
phosphate buffer
and .5M
phosphate buffer
phosphate buffer
Group 4:
Placebo
Treatment
10 Mice
-Oral Placebo
-Intraperitoneal
injection of .5M
phosphate
buffer
Figure 3: A survival curve shows the percentage of the
population that is alive in the hours since the administration
of the treatment.
Significance of the Research
-This research examines a life threatening
infection, therefore research on the topic is vital.
The infection associated with the medicine has
already claimed too many lives.
-The research will increase awareness, and allow
for more discussion of the infection, which will
expedite the diagnosis.
Flowchart taken from Meich 2005.
-C. sordellii is a gram positive, anaerobic, rod with two
known associated toxins. Hemorrhagic toxin, that
leads to excessive bleeding, and lethal toxin, which
leads to death (Bitti 1996).
-C. sordellii infection presents with acidosis,
hypothermia, flu like symptoms, including cramping
(Bitti 1996 and McGregor 1989).
Opportunities for Future Research
Aim 1:
IgA Serum
analysis through
ELISA
(Figure 1)
Aim 2:
Bacterial load
testing with CFU
analysis
(Figure 2)
Aim 3:
Time of death
recording
(Figure 3)
-Symptoms of the procedure include heavy bleeding,
abdominal pain, flu like symptoms, cramping, and
fever (Danco Laboratories 2005).
-Testing with mice has been practiced before in this
type of research with this bacteria as well. The
bacteria can also be filtered into an injectable form.
This is commonly used intraperitoneally (Bitti 1996).
-The research also provided a dosage scale for the
proposed animal model of 1ug/km(RxList).
-Possible replacements for mifepristone and misoprostol
within Mifeprex, to minimize the effects on the immune
system, while maintaining the same effects as a
medicinal abortion.
-Discovery of a way to increase immune response, as a
possible pretreatment for those seeking the procedure.
Statistical analysis for significance of data through
ANOVA procedure
Expected Results
-More research into the use of antitoxin in treatment of
patients who do develop the blood infection.
Literature Cited
Bitti, A., Mastrantonio, P., Spigaglia, P., Urru, G., Spano, A., Moretti, G., Cherchi, G. 1997. A fatal
postpartum Clostridium Sordellii associated toxic shock syndrome. Journal of Clinical Pathology
50(3):259-260.
Danco Laboratories. 2005. Medication guide for mifeprex.
Hypothesis
Misoprostol has an inhibitory effect on the immune
system, and that will lead to increased bacterial
load, and more rapid death.
Aim 1: To determine the effect of misoprostol on
the immune system by examining IgA reduction.
Aim 2: To determine if the bacterial load of an
infection is effected by the presence of misoprostol.
Aim 3: To determine if the drug leads to more
rapid death.
-Future research could include an investigation of the
combination of the medicines and the immune system’s
reaction.
El-Refaey, H., Rajasekar, D., Abdalla, M., Calder, L., Templeton, A., 1995. Induction of abortion with
mifepristone and oral or vaginal misoprostol. New England Journal of Medicine 332(15):983-987.
McGregor, J., Soper, D., Lovell, G., Todd, J., 1989. Maternal deaths associated with Clostridium
soredellii infection. American Journal of Obstetrics and Gynecology 161(4):987-995.
Miech, R. 2005. Pathophysiology of mifepristone induced septic shock due to Clostridium sordellii.
The Annals of Pharmacotherapy. 39.
RxList. Drug Description of Mifeprex. http://www.rxlist.com/mifeprex-ru486-drug.htm. Accessed
online
on
8
October
2008.
Figure 1: Table shows the amount of IgA
present in the blood of the mice.
Figure 2: Shows the amount of colony
forming units of C. sordellii that are able
to be isolated from the mouse’s blood.
Acknowledgements
I would like to thank Dr. K for all his help and Planned Parenthood for all their input.
Also thank you to my parents for listening to me talk about Senior Thesis for the past 4
years.