Age: 25.0
Sex: F
Vaccine: MNQ, MNQ
Symptoms: Urine analysis abnormal, Vaginal haemorrhage
Clinical narrative: Initial report received on 26 February 2008 regarding study protocol P1065 (Reference number: EAE-2008-0175). The following is verbatim from that report: "Summary: The subject is a 25 year-old Gravida 2 Para 1, 1 cesarean section, HIV infected, African American female, who enrolled in the protocol on August 17, 2007. On November 27, 2007, she experienced grade 3 miscarriage. The subject had negative pregnancy tests at study screening on August 17, 2007 and at study entry on August 24, 2007. She also admitted to using birth control as required by the study. On August 17, 2007, at screening, the subject's viral load was 1280 copies/mL. On August 24, 2007, she received the first dose of the study agent, Menactra vaccine. On September 04, 2007, she reported to the clinic where a pregnancy test performed was positive. It was then decided that the subject would not receive any further doses of the study agent but continue with her study visit. On September 17, 2007, at 6 weeks gestation, the subject went to the emergency room with complaints of vaginal bleeding and abdominal cramping. An abdominal ultrasound revealed threatened abortion. Blood work done revealed she is blood group O Rhesus positive. A urinalysis was positive for blood (2+), nitrates numerous bacteria and 3 epithelial cells. She was diagnosed with urinary tract infection and treated with Nitrofurantoin. However, she continued to have cramping and vaginal bleeding through out her pregnancy. On November 27, 2007, the subject was seen by her gynecologist for a routine visit. An abdominal ultrasound was performed which revealed a fetal demise at 12 weeks gestation. On December 02, 2007, she began bleeding vaginally. She was rushed to the hospital and a dilatation and curettage was performed. The subject was discharged the same day." "Assessment of relationship: The site Principal Investigation has assessed the event of miscarriage as probably not related to the study report, Menactra vaccine. The Medical Officer has assessed the event of miscarriage as probably not related to, but could not rule out the relationship to the study agent, Menactra. After review of the clinical details and investigator comments pertaining to this adverse event, and based upon our experience with the agent, the agency does not believe that changes to the conduct for this trial are warranted." "Previous Reports: There has been one similar safety report previously submitted under this IND: Serial #006, Submitted October 24, 2007, EAE# 2007-1346. "Patient history and clinical evaluation, Clinical evaluation: The subject is a 25-year-old, Gravida Para 1, 1 cesarean section, HIV infected, female, who enrolled in the P1065 study on August 17, 2007. On November 27, 2007, the subject experienced grade 3 miscarriage. The subject was diagnosed with HIV infection in 2003 and had been on Zidovudine/Lamivudine and Nelfinavir since July, 2005. On August 17, 2007, during screening, the subject's viral load was 1280 copies/mL and CD4 cell count was 725 cells/mm^3 (normal range 484-1159). A pregnancy test performed was negative. She was on oral contraceptive pills and agreed to avoid pregnancy as required by the study. On August 24, 2007, at study entry, following a negative pregnancy test, the subject was started on the study agent, Menactra. On August 31, 2007, seven days post-vaccine injection, a follow-up visit was conducted by the study staff telephonically. The subject reported missing her menstrual period and stated that a self administered urine pregnancy test was positive. Her last menstrual period was on August 2, 2007. On September 4, 2007, she reported to the clinic where a repeat pregnancy test was again positive. It was then decided that the subject would not receive any further doses of the study agent but continue with all study visit. On September 15, 2007, during her first prenatal visit to the gynecologist, the subject's antiretroviral therapy was changed form Zidovudine/Lamivudine and nelfinavir to Zidovudine/Lamivudine and Lopinavir/Ritonavir. On September 17, 2007, at 6 weeks gestation, the subject went to the emergency room with complaints of vaginal bleeding and abdominal pain, radiating to the back, without diarrhea or constipation. Physical examination revealed the subject's blood pressure was 114/72 mmHg, pulse was 69 beats per minute, respiration rate was 16 breaths per minute, temperature was 98 degrees Celsius and oxygen saturation was 100%. An abdominal ultrasound performed was consistent with the finding of threatened abortion. Laboratory results showed the subject's hemoglobin was 11.7g/dL, platelet was 385x10^3/uL, white blood cell count was 6.2x10^3/uL, and absolute neutrophil count was 3.3x 10^3/uL (no normal ranges provided). A urinalysis was positive for blood (2+), nitrates, numerous bacteria, red blood cells <1, white blood cells 4 and epithelial cells 3. She was diagnosed with urinary tract infections and treated with nitrofurantoin. She was also advised to start prenatal care and take prenatal vitamins. On November 27, 2007, the subject was seen by her gynecologist for a routine visit. An abdominal ultrasound was performed which showed a single intrauterine pregnancy, in vertex presentation was no fetal cardiac activity, no evidence of placenta previa and anterior location of the placenta. The length of the cervix was 2.3 centimeters. The findings were consistent with fetal demise at 12 weeks gestation. The subject was scheduled to have a dilatation and curettage on December 3, 2007. However, at 0300 hours on December 2, 2007, she began bleeding vaginally. She was rushed to the hospital and diagnosed with grade 2 hemorrhage. Dilatation and curettage was performed at 0800 hours. The subject was discharged the same day at 1500 hours. On February 7, 2008, the subject reported to the clinic for her scheduled week 24 study visit. It was during this visit that she reported the miscarriage to the study staff. Past medical history is significant for HIV infection and a cardiac murmur diagnosed in middle school which had resolved. The subject was taking concomitant medications Lamivudine/Zidovudine for two years and Lopinavir/Ritonavir for two months at the time of the event." "Assessment of relationship: The site Principal Investigator has assessed the event of miscarriage as probably not related to the study agent, Menactra. The Medical Officer has assessed the event of miscarriage as probably not related, but could not rule out the relationship to the study agent, Menactra. After review of the clinical details and investigator comments pertaining to this adverse event, and based upon our experience with the agent, the agency does not believe that changes to the conduct for this trial are warranted."