Chlamydial Cervicitis and HIV in Pregnancy Case File
Eugene C. Toy, MD, Patti Jayne Ross, MD, Benton Baker III, MD, John C. Jennings, MD
CASE 20
An 18-year-old G1P0 woman at 22 weeks’ gestation has a positive Chlamydia deoxyribonucleic acid (DNA) assay of the endocervix. She denies vaginal discharge, lower abdominal pain, or fever. On examination, her blood pressure is 110/70 mm Hg, heart rate is 70 beats per minute (bpm), and she is afebrile. Her heart and lung examinations are normal. Her abdomen is nontender and gravid. The fundal height is 20 cm and fetal heart tones are in the 140 bpm range. The gonococcal culture is negative and the Pap smear result is normal. Her human immunodeficiency virus (HIV) test by enzyme-linked immunosorbent assay (ELISA) is also positive.
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ANSWER TO CASE 20:
Chlamydial Cervicitis and HIV in Pregnancy
Summary: An 18-year-old G1P0 woman at 22 weeks’ gestation has a positive Chlamydia DNA assay of the endocervix, and a positive HIV ELISA test. She denies lower abdominal pain and is afebrile. Her abdomen is nontender and gravid. The gonococcal culture is negative.
- Next step in therapy: Oral erythromycin, azithromycin, or amoxicillin.
- Next diagnostic step for HIV: Either Western blot confirmation, or polymerase chain reaction (PCR) confirmation.
- Optimal treatment of HIV infection in pregnancy: Assessment of stage of HIV infection, initiation of highly active antiretroviral therapy (HAART), offer elective cesarean delivery, oral zidovudine to the neonate.
ANALYSIS
Objectives
- Understand that Chlamydia trachomatis is a common cause of cervicitis, and options of treatment in pregnancy.
- Know that chlamydial infections may lead to neonatal pneumonia or conjunctivitis if untreated.
- Understand the approach to screening for and treating HIV infection in pregnancy.
- Be aware of the relationship of HIV viral load on vertical transmission.
- Understand the approach to hepatitis B and C perinatal infection.
Considerations
This 18-year-old nulliparous woman at 22 weeks’ gestation has a positive DNA test for Chlamydia. These types of tests are often utilized because of their high sensitivity and specificity, yet lower cost as compared with chlamydial cultures. This patient has a chlamydial infection, which is more common than gonorrheal involvement; accordingly, her gonorrheal culture was negative. Chlamydial endocervical infection has not been proven to cause adverse problems with pregnancy, such as preterm labor or preterm premature rupture of membranes. It has been implicated in neonatal conjunctivitis and pneumonia. Interestingly, the erythromycin eye ointment given at birth does not prevent chlamydial conjunctivitis, although it does protect against gonococcal eye infection. Babies with documented chlamydial ophthalmic infections are given oral erythromycin for 14 days. Because it is mainly neonatal disease, that is the issue, an important time to screen for the organism would be the third trimester, close to the time of delivery. Treatment for the pregnant patient includes erythromycin or amoxicillin for 7 days or azithromycin as a one-time dose.
APPROACH TO:
Cervicitis and HIV in Pregnancy
DEFINITIONS
CHLAMYDIAL NEONATE INFECTION: Conjunctivitis or pneumonia acquired by inoculation during the birth process.
TETRACYCLINE EFFECT: Tetracycline compounds, such as doxycycline, taken by pregnant women can lead to yellow staining of the fetal teeth.
CLINICAL APPROACH
Chlamydia and Gonorrhea
Chlamydia trachomatis is an obligate intracellular organism with several serotypes. It is one of the most common sexually transmitted organisms in the United States, causing urethritis, mucopurulent cervicitis, and late postpartum endometritis. The majority of women, however, are asymptomatic. Vertical transmission may occur during the labor and delivery process, leading to neonatal conjunctivitis or pneumonia. It is unclear whether chlamydial infection of the cervix is associated with preterm labor or preterm rupture of membranes; thus, the main concern is for the neonate. Eye prophylaxis is effective for preventing gonococcal conjunctivitis but not chlamydial involvement. Chlamydial conjunctivitis is now the most common cause of conjunctivitis in the first month of life. Late postpartum endometritis, occurring 2 to 3 weeks after delivery, is associated with chlamydial disease.
Some risk factors for chlamydial infections include unmarried status, age under 25 years, multiple sexual partners, and late or no prenatal care. The discharge is often difficult to detect because of the increased cervical mucus in pregnancy. Direct fluorescent antibody tests and DNA detection tests using PCR are highly sensitive and specific, and less costly than culture. Treatment includes oral erythromycin, amoxicillin, or azithromycin. Tetracycline and doxycycline are contraindicated in pregnancy because of the possibility of staining of the neonatal teeth. Because reinfection is common, repeat testing is recommended in the third trimester.
Gonococcal infection may complicate pregnancy, especially in teens or those with a history of sexually transmitted disease. Gonococcal cervicitis is associated with abortion, preterm labor, preterm premature rupture of membranes, chorioamnionitis, neonatal sepsis, and postpartum infection. Disseminated gonococcal disease is more common in the pregnant women (especially the second or third trimester), presenting as pustular skin lesions, arthralgias, and septic arthritis. Untreated gonococcal ophthalmia can progress to corneal scarring and blindness. Chlamydia commonly is present in a patient who is infected with gonorrhea. Thus, the usual treatment for gonococcal cervicitis is ceftriaxone intramuscularly and an additional antibiotic for C. trachomatis, such as erythromycin.
HIV Infection
Efforts in public health in the United States have reduced the vertical transmission from 27% to less than 2%.The basic components include widespread HIV testing, counseling, antiretroviral therapy, viral load assessment, cesarean delivery when appropriate, and counseling to avoid breast feeding.
Heterosexual spread of HIV is the most common mode of transmission accounting for 72% of HIV transmission among women in the United States. Women of color account for 80% of HIV infections in women. HIV infection leads to progressive debilitation of the immune system, rendering infected individuals susceptible to opportunistic infections and neoplasias that rarely afflict patients with intact immune systems. Furthermore, the unborn fetus may become infected either by transplacental passage or during the delivery process. The neonate may also acquire HIV from infected breast milk. Because measures in pregnancy, during delivery, and postpartum can dramatically decrease the risk of vertical transmission to the fetus, HIV serostatus should be obtained on every pregnant woman as early as possible in pregnancy and repeated at the time of labor or delivery.
Up to 20% of HIV-infected pregnant women do not have prenatal care, and may present to labor and delivery units without treatment. Recently, the CDC has recommended that labor and delivery units consider using rapid HIV testing (results ready within 45 minutes) for those women with unknown HIV status, so that HIV infection can be identified and measures may be taken to reduce the risk of vertical transmission.
Initially, patients may either be asymptomatic or have symptoms that mimic a mononucleosis-like illness. Antibodies to the HIV virus are usually detectable 1 month after infection and are almost always detectable within 3 months. Antibody testing begins with a screening test, either an ELISA or a rapid test. A positive screening test is followed with a confirmatory test, either a Western blot or an immunofluorescence assay. A person is only considered positive for HIV after a confirmatory test has been performed. The standard antibody tests may take 3 to 5 days, while the rapid tests return results in minutes to hours. Fourth-generation assays for the simultaneous detection of HIV-1 p24 antigen and anti-IgG and IgM antibodies for HIV-1/ HIV-2. Because p24 antigen can be detected 2 to 4 weeks after HIV exposure, the window period for accurately diagnosing HIV status is significantly reduced. A reactive HIV-1/2 antigen/ antibody combination immunoassay requires further testing to differentiate HIV-1 versus HIV-2 antibodies; an HIV-1 negative or indeterminate antibody test should be followed up by an HIV-1 nucleic acid test (for antigen).
Studies have been unable to determine, with certainty, the effect of pregnancy on HIV disease progression. There continues to be correlation between maternal disease stage at the time of diagnosis with the viral load and transmission rates. When loads are reduced to undetectable levels, transmission to the fetus becomes uncommon. Viral load and CD4 T-cell testing are ways to monitor a woman’s health status. In pregnancy, the viral load should be evaluated monthly until it is no longer detectable. The goal in pregnancy is to maintain a viral load under 1000 ribonucleic acid (RNA) copies per milliliter. In women with viral loads exceeding 1000 RNA copies/mL, scheduled cesarean (prior to labor or ROM) has been shown to significantly reduce the risk of vertical infection.
Combination retroviral therapy decreases the risk of perinatal transmission to <2%, and the best route of delivery is not clear. There is some evidence that cesarean delivery can further decrease vertical transmission, but cesarean delivery increases maternal risks of infection and hemorrhage. Thus, HIV-positive women with viral load counts below 1000 copies/mL should be carefully counseled. Those HIV-infected women who choose to deliver vaginally should receive intravenous zidovudine (ZDV) during labor. Breast feeding should be discouraged. The neonate should also receive oral ZDV syrup.
Antiviral Therapy
Treatment regimens include polytherapy (usually consisting of nucleoside reverse transcriptase inhibitor [NRTI] such as zidovudine, and a protease inhibitor [PI] or less commonly non-nucleoside reverse transcriptase inhibitor [NNRTI]) to decrease resistance. NRTIs cross the placenta and are classes B and C. Patients should have regular monitoring of liver function tests and blood counts to detect toxicity. The use of protease inhibitors may slightly increase the risk of prematurity, and there may be a slight association of HAART and preeclampsia. Nevertheless, the benefits generally far outweigh the risks. Antiviral therapy shows no increase in congenital anomalies with the exception of efavirenz, an NNRTI, which is associated with neural tube defects.
Hepatitis Testing
Hepatitis B surface antigen testing is recommended for all pregnant patients. Those with co-infection should be treated with antiviral agent such as tenofovir and lamivudine. Infants should receive hepatitis B immunoglobulin (Ig) at birth and start the vaccination within 12 hours of birth. Up to 50% of HIV-infected individuals are coinfection with hepatitis C (HCV); confirmation is by hepatitis C antibody by ELISA. Deciding whether to treat hepatitis C with interferon and/ or ribavirin in pregnancy is complicated; ribavirin is associated with fetal anomalies when given around the time of conception of both men and women (category X). Coinfection with HIV increases the risk of neonatal infection with hepatitis C, and multidrug antiviral therapy may reduce this risk. Women who are not HIV infected with either hepatitis B or hepatitis C may breast feed. Cesarean has not been shown to affect transmission.
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CASE CORRELATION
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COMPREHENSION QUESTIONS
20.1 Which of the following is a characteristic of chlamydial infection?
A. It has a characteristic appearance on Gram stain.B. It has a propensity for transitional and columnar epithelia.C. It causes neonatal pneumonia, usually with a high fever and sepsis.D. It is one of the leading causes of deafness worldwide.
20.2 Which of the following statements is True regarding C. trachomatis infections?
A. The organism has a fairly rapid replication cycle, about 6 hours.B. It is an obligate intracellular organism.C. Erythromycin eyedrops are an effective means of preventing chlamydial conjunctivitis.D. It is associated with acute early endometritis.E. it is a cause of infectious arthritis.
20.3 A 28-year-old parous woman at 16 weeks’ gestation is noted to have a positive Chlamydia assay of the endocervix. She is asymptomatic. Which of the following is an acceptable treatment?
A. Intramuscular azithromycinB. Intramuscular ceftriaxoneC. Oral amoxicillinD. Oral ciprofloxacinE. Oral doxycycline
20.4 An 18-year-old G1P0 woman at 38 weeks’ gestation comes into the obstetrical unit in active labor. She denies leakage of fluid. She states that she is HIV infected, but had not received any medications or prenatal care. She is 5-cm dilated. Which of the following is the most appropriate step?
A. Immediate cesarean deliveryB. Intravenous acyclovir and allow laborC. Intravenous zidovudine and allow laborD. Rupture of membranes, placement of fetal scalp electrode, and uterine contraction monitor
20.5 A 27-year-old woman has been diagnosed with an HIV infection based on a positive ELISA and confirmed by the Western blot analysis. Which of the following is the most likely method that the patient became infected?
A. Exposure to infected blood via splash contaminationB. Heterosexual intercourseC. Homosexual intercourseD. Intravenous drug useE. Renal dialysis center
20.6 A 34-year-old G1P0 woman at 16 weeks’ gestation comes in for her first prenatal visit. Her hepatitis B surface antigen is positive. Which of the following is the best next step?
A. Advise to terminate pregnancyB. Start multidrug antiviral therapyC. Administer hepatitis B immune globulinD. Ultrasound of the liverE. Liver function tests and further hepatitis serology
20.7 A 32-year-old G2P1 woman who is at 8 weeks’ pregnant states that she has hepatitis C. Her HIV test is negative. She asks what can be done to reduce the risk of hepatitis C to her unborn baby. You recommend:
A. Avoid breast feedingB. Initiate ribavirin antiviral therapyC. Avoid invasive proceduresD. Recommend cesarean delivery
ANSWERS
20.1 B. Chlamydia is not typically seen on Gram stain because it is an intracellular organism. It does have a propensity for columnar and transitional epithelia, and it is a leading cause of preventable blindness worldwide. It can cause neonatal pneumonia or conjunctivitis. However, the presentation of the pneumonia is not typically associated with high fever or sepsis.
20.2 B. Chlamydia is an obligate intracellular organism associated with late postpartum endometritis and has a long replication cycle. Erythromycin eyedrops are an effective means of preventing gonococcal eye infection but chlamydial infection must be treated systemically with erythromycin. Gonococcal cervicitis is more likely to disseminate during pregnancy, and a patient may present with septic arthritis, arthralgias, and pustular skin lesions.
20.3 C. Oral amoxicillin is well tolerated and effective treatment of chlamydial cervicitis in pregnancy. Oral azithromycin can be tolerated as well. Erythromycin estolate can lead to liver dysfunction in pregnancy; thus, the estolate salt is contraindicated in pregnant women. Intramuscular ceftriaxone is used to treat gonococcal cervicitis. Doxycycline, or tetracycline, is contraindicated in pregnancy because of the possibility of staining neonatal teeth. Ciprofloxacin is also contraindicated in pregnancy because it may lead to neonatal musculoskeletal problems.
20.4 C. Because labor has already begun, elective cesarean delivery will not affect vertical transmission. In other words, the cesarean would need to be performed prior to rupture of membranes or labor to effectively decrease vertical transmission. Intravenous ZDV and minimizing trauma to the baby, such as avoiding fetal scalp electrode, intrauterine pressure catheters, forceps, and vacuum delivery, is advisable. Acyclovir is used to prevent viral shedding in patients infected with HSV. The neonate generally also receives oral ZDV syrup.
20.5 B. The most common method of HIV transmission to women in the United States is currently heterosexual intercourse.
20.6 E. When a patient has a positive hepatitis B surface antigen result, it means the individual has replicating virus; the next step is to determine the stage: acute, chronic, or chronic carrier. Liver function tests and IgM hepatitis B core Ab, and hepatitis B e antigen and antibody can help to make this determination.
20.7 C. Vertical transmission increases with high viral load, prolonged rupture of membranes, and invasive procedures. Cesarean does not affect the risk of neonatal infection. Fetal scalp electrodes should be avoided if possible. Breast feeding does not seem to increase the risk of transmission unless there is cracked or bleeding nipples. Antiviral therapy is usually not used in pregnancy due to the side effects; ribavirin in particular is category X and usually avoided in pregnancy.
CLINICAL PEARLS
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» The best treatments for chlamydial cervicitis in pregnancy are erythromycin, azithromycin, and amoxicillin. » Chlamydia can cause conjunctivitis or pneumonia in the neonate. » Ophthalmic antibiotics administered to the neonate help to prevent gonococcal disease but not chlamydial conjunctivitis. » The most common mode of HIV transmission in women is through heterosexual contact. » Women account for the majority of cases of HIV transmission in the United States. » With widespread prenatal testing for HIV, use of HAART, cesarean delivery when viral load is high, zidovudine to the neonate, and avoiding breast feeding, vertical transmission is now below 2% in the United States. » When born to a mother with hepatitis B surface antigen positive, hepatitis B immunoglobulin and vaccine should be given to a neonate within several hours of birth. » The vertical transmission of hepatitis C vertical depends on viral load especially in the third trimester, coinfection with HIV, prolonged rupture of membranes, and invasive procedure. » Cesarean delivery does not affect the perinatal transmission of hepatitis C. |
REFERENCES
American College of Obstetricians and Gynecologists. Gynecologic care of women with HIV. The ACOG Practice Bulletin 117. Washington, DC; 2010. (Reaffirmed 2015.)
American College of Obstetricians and Gynecologists. Routine human immunodeficiency virus screening. ACOG Committee Opinion 411. Washington, DC; 2008.
American College of Obstetricians and Gynecologists. Scheduled cesarean delivery and the prevention of vertical transmission of HIV infection. ACOG Committee Opinion 234. Washington, DC; 2000. (Reaffirmed 2010.)
Castro LC, Ognyemi D. Common medical and surgical conditions complicating pregnancy. In: H acker NF, Gambone JC, Hobel CJ, eds. Essentials of Obstetrics and Gynecology. 5th ed. Philadelphia, PA: Saunders; 2009:191-218.
Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Gilstrap LC III, Wenstrom KD. Sexually transmitted diseases. In: Williams Obstetrics. 24th ed. New York, NY: McGraw-Hill; 2014:1235-1258.
Gibbs RS, Sweet RI, Duff PW. Maternal and fetal infectious disorders. In: Creasy RK, Resnik R, Iams JD, eds. Maternal–Fetal Medicine. 6th ed. Philadelphia, PA: Saunders; 2009:362-384.
Minkoff HL. Human immunodeficiency virus. In: Creasy RK, Resnik R, Iams JD, eds. Maternal–Fetal Medicine. 6th ed. Philadelphia, PA: Saunders; 2009:803-813.
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