Part I: Maternal Medical Complications Cardiology 1. Hypertensive disorders
A. Marie O’Neill 37. Group B Streptococcus
KEY POINTS
l Pregnant women colonized with Trichomonas vaginalis in the second trimester have ahigher risk of delivering an infant with low birth weight or delivering before term, but unfortunately metronidazole treatment has beenassociated with an increased risk of preterm birth.
l T. vaginalisinfection is a risk factor for sexual transmis- sion of HIV-1, with a twofold increase reported.
l Condoms,when used correctly and consistently, provide a high degree ofprotection from many STIs, includingT.
vaginalis.
l There is no evidence that identifying asymptomatic T.
vaginalis is beneficial in reducing the associated risk of preterm delivery or delivery of a low-birth-weight infant.
Therefore, there is insufficient evidence to recommend screening of asymptomatic pregnant women, and some evidence thattreatment of these patients may in fact be harmful.
l Metronidazole as a single 2-g oral dose, or 500 mg twice a day for seven days,at any gestational ageis the treat- ment of choice forsymptomaticT. vaginalisinfection.
l Concurrent treatment of sexual partnersis recommended to prevent reinfection.
EPIDEMIOLOGY/INCIDENCE
Worldwide, it is estimated that 180 million new cases of trichomoniasis occur annually (1). Developing countries account for a disproportionate number of cases. Trichomonia- sis affects 2 to 3 million women and approximately 80,000 pregnant women in the United States annually. The frequency of infection in European women is similar. The WHO esti- mates 30 million new infections annually in Africa (2). In contrast to bacterial STIs such as Neisseria gonorrhoeae and Chlamydia trachomatis, T. vaginalis infection rates are as high or higher in middle-aged women when compared to adoles- cents. Incidence is highest among women with multiple sexual partners, and in populations with high rates of other sexually transmitted infections.
SYMPTOMS/SIGNS
The clinical manifestations of trichomoniasis are unchanged in pregnant women. Infection isasymptomatic in up to 50% of women. The most common symptoms include vulvovaginal pruritis (23–82%), vaginal discharge (50–75%), dysuria (30–50%), and dyspareunia (10–50%). The most common signs are copious vaginal discharge (50–75%) (yellow/green in 5–20%, frothy in 10–50%), inflammation of vaginal mucosa (40–75%), and vulvar erythema (10–20%).
PATHOPHYSIOLOGY/ETIOLOGY
Trichomoniasis is caused by the protozoanT. vaginalis, which had been previously thought to be a harmless commensal.T.
vaginalis can infect the vagina and the Skene’s glands of the urethra. The incubation period forT. vaginalisis 4 to 7 days on average, but ranges from 2 to 28 days.
TRANSMISSION
T. vaginalis is easily transmitted duringvaginal intercourse.
The organism will survive for several hours in moist environ- ment outside the host and is rarely transmitted nonvenerally.
The transmission rate from male to female during vaginal intercourse has been reported to be 66% to 100% (3). Vertical transmission to a female infant occurs in 2% to 17% if vaginal infection is present at the time of delivery (4).
COMPLICATIONS/RISKS
Pregnant women colonized with T. vaginalis in the second trimester had a 30%higher risk of delivering an infant with low birth weightordelivering before term, and a 40% higher risk of giving birth to an infant who was both pretermandof low birth weight (5). In pregnant women with T. vaginalis, unfortunatelymetronidazole treatment (two 2-g doses given 48 hours apart at 16–23 weeks) has beenassociated with an 80% increase of preterm birthcompared to no treatment, with the majority of the increase in preterm delivery attributed to spontaneous preterm labor (6–8). The proposed mechanism for treatment with metronidazole causing preterm labor is that lysis of dying trichomonads elicits an inflammatory response that triggers labor (6–8) (see also chap. 16,Obstetric Evidence Based Guidelines).
T. vaginalisinfection is arisk factor for sexual transmis- sion of HIV-1in women. Studies from Africa have suggested that T. vaginalis infection approximately doubles the rate of HIV transmission (9). The proposed mechanism for this increased risk is twofold: local infiltration of large number of leukocytes including CD4+ lymphocytes—the primary target of HIV infection—and disruption in the integrity of the vaginal mucosa allowing access to viral particles. HIV-positive women who become infected with T. vaginalis have been shown to shed more HIV virus in their vaginal secretions, and therefore pose a higher risk for transmission.
Epidemiologic studies of T. vaginalis infection in the neonate have reported vertical transmission rates ranging from 0.1% to 4.8% (4), causing vaginal, urinary, and respira- tory infection in these neonates.
MANAGEMENT Prevention
Condoms, when used correctly and consistently, provide a high degree of protection from many STIs(10).
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Most cases of reinfection result from sexual contact with an untreated partner. Adequate treatment of sexual partners has been shown to decrease reinfection (11).
Screening
There is no evidence that identifying asymptomatic T. vaginalis is beneficial in reducing the associated risk of preterm delivery or delivery of a low-birth-weight infant.
Diagnosis
Wet mount preparation of vaginal secretions suspended in normal saline with microscopic observation of motile tricho- monads is the mostcommonly utilizedmethod of diagnosing trichomoniasis in women; however, the sensitivity of this method islow.
Isolation ofT. vaginalisbyculture is the gold standard, but the greater cost and longer time to diagnosis make this an underutilized diagnostic option. Commonly used culture media include (12,13):
To increase the detection rate in a high-risk population without substantially increasing cost, culture could be performed on those symptomatic patients with a negative wet mount.
Although nucleic acid–based tests are available, they are not yet widely used. Conventional Pap smear is not considered accurate for the identification of T. vaginalis. Confirmatory testing is necessary for those cases reported by Pap: sensitivity
= 60% to 70%, specificity = 88%. Liquid-based Pap smear is accurate for the identification of T. vaginalis and warrants treatment without further testing; however, the sensitivity is low (61.4%) (14). Clinicians who perform STD screening tests should be aware of the prevalence of STDs in the population being screened and have a conceptual understanding of pos- itive predictive value and the impact screening low-risk indi- viduals has with a test that has limited specificity (Table 36.1) (15–17).
PCR and nucleic acid amplification tests that can be performed as rapid point of care testing are commercially available outside of the United States. To date, none of these assays are FDA approved.
Treatment
The nitroimidazoles are the only class of drugs useful for the oral or parenteral treatment of trichomoniasis. In randomized clinical trials, oral nitroimidazoles have resulted in parasito- logic cure rates of 90% to 95%. Metronidazole and tinidazole are most commonly used.Metronidazole can be given as a single 2-g oral dose, or 500 mg twice a day for seven days, and can be given to symptomatic womenat any gestational age(7).
Multiple studies and meta-analyses have not demonstrated a definitive association between metronidazole use during preg- nancy and teratogenic or mutagenic effects in infants (18,19).
Tinidazole is given as a single 2-g oral dose. Its use is contra- indicated in the first trimester of pregnancy. Metronidazole resistance is increasingly common. The CDC estimated that5%
of clinical isolates of T. vaginalis exhibit some degree of metronidazole resistance. An escalated dosing regimen of metronidazole 2 g daily for three to five days has been suc- cessful in some cases of resistant infection, but in generalnot more than a single 2-g dose should be given to prevent possible increase in preterm birth(7). Tinidazole is effective in treating up to 60% of metronidazole-resistant T. vaginalis infections.Concurrent treatment of sexual partnersis recom- mended to prevent reinfection.
REFERENCES
1. World Health Organization. World Health Report 1998. Geneva, Switzerland: WHO, 1998. [Epidemiologic data]
2. Gerbase AC, Mertens TE. Sexually transmitted diseases in Africa:
time for action. Afr Health 1998; 20(3):10–12. [Review]
3. Krieger JN. Trichomoniasis in men: old issues and new data. Sex Transm Dis 1995; 22(2):83–96. [II-3]
4. Danesh IS, Stephen JM, Gorbach J. NeonatalTrichomonas vaginalis infection. J Emerg Med 1995; 13(1):51–54. [II-3]
5. Cotch MF, Pastorek JG II, Nugent RP, et al.Trichomonas vaginalis associated with low birth weight and preterm delivery. The Vaginal Infections and Prematurity Study Group. Sex Transm Dis 1997; 24(6):353–360. [II-2]
6. Klebanoff MA, Carey JC, Hauth JC, et al. Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection. N Engl J Med 2001; 345(7):487–493. [RCT;n= 617. 2 g metronidazole q48h2 doses]
7. Gulmezoglu AM. Interventions for trichomoniasis in pregnancy.
Cochrane Database of Syst Rev 1, 2011. [Meta-analysis; two RCTs;
n= 842]
8. Ross SM, Van Middelkoop A. Trichomonas infection in preg- nancy: does it affect outcome? S Afr Med J 1983; 63:566–567.
Modified Diamond’s broth media Sensitivity 95%
InPouchTMtransport and test system Sensitivity 87%
Modified Columbia agar Sensitivity 98%
Table 36.1 Screening/Diagnostic Tests forT. vaginalis
Sensitivity (%) Specificity (%) Advantages Disadvantages
Wet mount 62–80 >99 l Rapid results
l Inexpensive
l High specificity
l Low sensitivity compared to culture
l Sensitivity and specificity are strongly dependent on the skills and experience of the microscopist and also on the quality of the sample
Culture 95 100 l High sensitivity and specificity l Organism can be rendered nonviable if incorrect media used or delay in transport
l 3–7 days to complete
l Not available in most clinical labs
PCR/NAAT 95 98 l Results available more quickly
than with culture
l Most expensive option
l Limited availability Abbreviations: PCR, polymerase chain reaction; NAAT, nucleic acid amplification test.Source: From Refs. 15–17.
TRICHOMONAS 261
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[RCT;n= 225; 2 g metronidazole1 dose to women and their partners]
9. Laga M, Manoka A, Kivuvu M, et al. Non-ulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study. AIDS 1993; 7(1):95–102.
[II-2]
10. Paz-Bailey G, Koumans EH, Sternberg M, et al. The effect of correct and consistent condom use on chlamydial and gonococcal infection among urban adolescents. Arch Pediatr Adolesc Med 2005; 159(6):536–542. [II-3]
11. Schwebke JR, Desomnd RA. A randomized controlled trial of partner notification methods for prevention of Trichomonas in women. Sex Transm Dis 2010; 37:392–396. [RCT,n= 484]
12. Borchardt KA, Zhang MZ, Shing H, et al. A comparison of the sensitivity of the InPouch TV, diamond’s and trichosel media for detection of Trichomonas vaginalis. Genitourin Med 1997; 73 (4):297–298. [II-2]
13. Stary A, Kuchinka-Koch A, Teodorowicz L. Detection ofTricho- monas vaginalison modified Columbia agar in the routine labo- ratory. J Clin Microbiol 2002; 40(9):3277–3280. [II-2]
14. Lara-Torre E, Pinkerton JS. Accuracy of detection ofTrichomonas vaginalisorganisms on a liquid-based Papanicolaou smear. Am J Obstet Gynecol 2003; 188(2):354–356. [II-2]
15. Radonjic IV, Dzamic AM, Mitrovic SM, et al. Diagnosis of Trichomonas vaginalisinfection: the sensitivities and specificities of microscopy, culture and PCR assay. Eur J Obstet Gynecol Reprod Biol 2006; 126: 116–20. [II-2]
16. Aslan DL, Gulbahce HE, Stelow EB, et al. The diagnosis of Trichomonas vaginalisin liquid-based pap tests: correlation with PCR. Diagn Cytopathol 2005; 32(6):341–344. [II-3]
17. Patel SR, Wiese W, Patel SC, et al. Systematic review of diagnostic tests for vaginal trichomoniasis. Infect Dis Obstet Gynecol 2000;
8(5–6):248–257. [Review]
18. Burtin P, Taddio A, Ariburnu O, et al. Safety of metronidazole in pregnancy: a meta-analysis. Am J Obstet Gynecol 1995; 172(2 pt 1):525–529. [Meta-analysis]
19. Sorensen HT, Larsen H, Jensen ES, et al. Safety of metronidazole during pregnancy: a cohort study of risk of congenital abnormal- ities, preterm delivery and low birth weight in 124 women. J Antimicrob Chemother 1999; 44(6):854–856. [II-2]
262 MATERNAL-FETAL EVIDENCE BASED GUIDELINES
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37
Group B Streptococcus