Investigation of Clostridium sordellii Blood Infection Associated With Medicinal

Abortions Christine Humphrey

York College of Pennsylvania, Department of Biological Sciences

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.

Project Summary

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.

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.

Review of Literature Research Design

Literature CitedBitti, 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.

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.

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.

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. Opportunities for Future

Research-Future research could include an investigation of the combination of the medicines and the immune system’s reaction.

-Possible replacements for mifepristone and misoprostolwithin 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.

-More research into the use of antitoxin in treatment of patients who do develop the blood infection.

10 Mice-Oral Placebo

-Intraperitoneal

injection of .5M

phosphate buffer

40 BALB/c mice at the same gestation period

Group 3: Misoprostol

and C. sordellii Filtrate

Group 2: C. sordellii

Filtrate Treatment

Group 1: Misoprostol Treatment

Group 4:Placebo

Treatment

10 Mice-1ug/kg of

misoprostol-Intraperitoneal injection of .5M

phosphate buffer

10 Mice-1ug/kg of

misoprostol-

Intraperitoneal injection of

1:50 dilution of filtrate

and .5M phosphate

buffer

10 Mice -Oral Placebo

-Intraperitoneal

injection of 1:50 dilution of

filtrate and .5M

phosphate buffer

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)

Statistical analysis for significance of data through ANOVA procedure

-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).

-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).

Expected Results

Expected Results

Figure 1: Table shows the amount of IgApresent 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.

Figure 3: A survival curve shows the percentage of the population that is alive in the hours since the administration of the treatment.

Flowchart taken from Meich 2005.

http://www.farrin.com/drugs-and-products/drug-recalls.phphttp://www.health-insurance.org/rare-deadly-diseases