Chapter 17 – Genital Chlamydia trachomatis and Bacterial Vaginosis




Abstract




Chlamydia trachomatis genitourinary infection is a sexually transmitted infection affecting the uterus, the salpinges, the cervix, the urethra and the epididymis.


The infection is the most commonly reported bacterial sexually transmitted disease (STD) in the United States and a leading cause of infertility in women.


It can cause several sequelae, including chronic pelvic pain, pelvic inflammatory disease (PID) and tubal factor infertility.


Chlamydia trachomatis is commonly diagnosed in pregnancy. It has been linked to several pregnancy complications (premature rupture of membranes (PROM), preterm labour and birth, low birthweight, intrauterine growth retardation and postpartum endometritis).


In infected pregnant women, infants are at risk for acquiring C. trachomatis pneumonitis, conjunctivitis and nasopharyngeal infection.





Chapter 17 Genital Chlamydia trachomatis and Bacterial Vaginosis


Adel Elkady , Prabha Sinha and Soad Ali Zaki Hassan



Introduction


Chlamydia trachomatis genitourinary infection is a sexually transmitted infection affecting the uterus, the salpinges, the cervix, the urethra and the epididymis.


The infection is the most commonly reported bacterial sexually transmitted disease (STD) in the United States and a leading cause of infertility in women.


It can cause several sequelae, including chronic pelvic pain, pelvic inflammatory disease (PID) and tubal factor infertility.


Chlamydia trachomatis is commonly diagnosed in pregnancy. It has been linked to several pregnancy complications (premature rupture of membranes (PROM), preterm labour and birth, low birthweight, intrauterine growth retardation and postpartum endometritis).


In infected pregnant women, infants are at risk for acquiring C. trachomatis pneumonitis, conjunctivitis and nasopharyngeal infection.



Bacteriological Background


Genera Chlamydia bacteria (Chlamydia trachomatis, Chlamydophila pneumoniae and Chlamydophila psittaci) are microscopic unicellular prokaryotic organisms characterised by the lack of a membrane-bound nucleus and membrane-bound organelles.1


Chlamydiae are small, aerobic, gram-negative obligate intracellular micro-organisms that need oxygen to grow.2 Chlamydia depend on the host cell for intermediates, including adenosine triphosphate (ATP).


C. trachomatis has 18 serologically variant strains (serovars based on monoclonal antibody-based typing assays).


These serovars are associated with different medical disorders.




  • Serovars A, B, Ba and C cause a serious eye disease (trachoma) characterised by chronic conjunctivitis which if untreated may lead to blindness.



  • Serovars D–K cause genital infections; in women they are a common cause of cervicitis, urethritis, endometritis, salpingitis and perihepatitis.2



  • Serovars L1–L3 cause genital ulcers (Lymphogranuloma venereum (LGV)).3



Incidence and Prevalence of Chlamydia Infection during Pregnancy


Worldwide prevalence studies of C. trachomatis in pregnant women suggest similar if not higher rates than in non-pregnant women. In Africa, prevalence in pregnant women is up to 31.1 per cent,3 and in Asian countries the reported prevalence rates varied between 4.9–14 per cent and 41–44 per cent.4


Certain groups of women are at increased risk: those receiving care at public health clinics, young women and those with multiple sexual partners.


In a study in the USA, of a prospective cohort of 125 pregnant adolescents (12–18 years), 19 per cent were diagnosed at booking for prenatal care. Nine per cent had a recurrent infection, and 4 per cent were diagnosed with new C. trachomatis only on repeat testing. This study also shows that the infection may arise de novo during pregnancy.5 [EL 2]



Risk Factors for Chlamydia Infection during Pregnancy



Age <25 Years


The young sexually active population is consistently associated with increased risk of chlamydial infection.6


Twenty-nine of 34 studies of females and five of seven studies of males have shown a significant relationship between age and chlamydial infection in a multivariate analysis.7 [EL 1]


The increased prevalence in adolescents may also often be attributed to differences in sexual behaviours, multiple premarital relations, multiple sexual partners and unsafe sex practices.8



Marital Status


Chlamydia infection rates tend to be highest in women who are single and have had multiple sexual partners.9



Race, Ethnicity and Social Status


In the United States, data show higher rates of reported STDs among some racial or ethnic minority groups when compared with the white population.



Sexual Partners




  • Two-thirds of partners of people testing positive for chlamydia will also test positive.



  • Two or more sexual partners in the preceding year increases the risk.



  • The length of time between partnerships (‘gap’) is an important determinant of the overall transmission of STD.



  • A rapid recent change in sexual partners (a positive gap) who may have had an undiagnosed or untreated chlamydia infection also plays a role in increasing the risk of infection.10



Infection with Another Sexually Transmitted Infection (STI)


Other risk factors include having an STI in the past or currently.



Maternal Implications




  • As many as 85–90 per cent of infected men and women are asymptomatic.



  • C. trachomatis has been implicated with maternal infections in the post-abortal, post-caesarean section, puerperal sepsis and PID.



  • These complications are particularly relevant to elective termination surgery. In a study in Denmark, in women undergoing elective termination of pregnancy, 15 out of 23 chlamydia-infected women (65.20 per cent) developed acute PID.11 [EL 2]



  • A recent meta-analysis of 22 studies concluded that women infected with C. trachomatis have a higher risk of cervical cancer. Six studies suggested that co-infection of human papillomavirus (HPV) and C. trachomatis was related to a higher risk of uterine cervix cancer (OR = 4.03), thus stressing the need for screening and treatment of women with chlamydia infection, particularly those with HPV infection. [EL 1]12



Signs and Symptoms


Symptomatic women may describe vaginal discharge and dysuria (always consider chlamydia as a cause of sterile pyuria, which is the presence of 6–10 or more neutrophils per high-power field of unspun, voided mid-stream urine).


They may describe vague lower abdominal pain or fever. Dyspareunia, intermenstrual or post-coital bleeding has also been reported.


Physical examination may reveal:




  1. 1. A friable, inflamed cervix, sometimes with a follicular or ‘cobblestone’ appearance, with contact bleeding and/or mucopurulent endocervical discharge.



  2. 2. Abdominal pain.



  3. 3. Pelvic adnexal tenderness or cervical excitation may be elicited on bimanual palpation. Sometimes, chlamydial infection in women is suggested by inflammatory changes in their cervical cytology report and this may require follow-up.13


Non-genital chlamydia may present with a reactive arthritis, Reiter’s syndrome (urethritis, arthritis and conjunctivitis). In perihepatitis (Fitz-Hugh Curtis syndrome), upper abdominal pain is a presenting feature.


Symptoms in a male partner of any pregnant woman are an indication for STI screening of the couple.


Male partners may complain of urethritis with dysuria and urethral discharge or epididymo-orchitis presenting as unilateral testicular pain and/or swelling. Fever may also be a presenting feature in men.



Fetal Implications


The pathogenesis of C. trachomatis is still not well understood. Adverse pregnancy outcomes may be due to stimulating a fetal immunogenic response with cytokine release or causing an excessive maternal immunogenic response due to the homology of the human and chlamydial 60 kDa heat shock proteins (CHSP-60).14



1 Ectopic Pregnancy (EP)


Chlamydia infection can cause tubal damage (salpingitis, peritubal adhesions and intramural fibrosis) which predisposes to ectopic pregnancy and has been suggested by several studies.15 [EL 3]



2 Miscarriage


One study performed in Switzerland found that women with positive chlamydial serology had a 2.3 odds ratio for miscarriage compared to the control group. [EL 2]



3 Stillbirth


Data are scarce, but a few studies have shown a relation between stillbirth and chlamydia infections.


The odds ratio in one Australian study was estimated at 1.40.


C. trachomatis immunoglobulin (IgG) antibodies are frequently detected in sera from mothers with stillbirth.



4 Preterm Birth and/or Premature Rupture of Membranes




  • Preterm birth before 37 completed weeks is an important element of neonatal mortality and morbidity, with long-term adverse consequences for health. It occurs in 9.6 per cent of all births worldwide. Late sequelae of preterm births include cerebral palsy, sensory deficits, learning disabilities and respiratory illnesses, psychological and economic costs.



  • A US population-based cohort study raised the possibility that C. trachomatis is an important factor associated with PROM and preterm delivery, in women with C. trachomatis infection compared with those without infection.16 [EL 2]



  • A more recent Dutch study found that C. trachomatis detected by nucleic acid amplification tests (NAATs) was significantly associated with prematurity before 35 weeks of pregnancy, with a higher risk if infection occurs before 32 weeks.



5 Low Birthweight and Small for Gestational Age


Low birthweight is defined as weight below 2500 g; small for gestational age (SGA) is defined as birthweight less than 2 standard deviation scores (SDSs) below the mean for gestation.


A population-based, non-interventional, prospective cohort study showed that neonates born to chlamydia-positive women had, on average, a lower birthweight (<2500 g), especially when prematurely born. However, the difference did not reach statistical significance.



Neonatal Chlamydia




  1. 1. Neonatal chlamydial infection is a significant cause of neonatal morbidity.



  2. 2. Following passage through an infected birth canal, neonates have a significant risk of acquiring C. trachomatis ophthalmia neonatorum (ON) and conjunctivitis (18–50 per cent), pneumonitis (3–18 per cent) and nasopharyngeal infection (15–20 per cent).17



  3. 3. Neonatal infection occurs because of vertical transmission from an infected mother at the time of delivery.



  4. 4. The mother-to-child vertical transmission rate is higher after vaginal birth and can be as high as 50–60 per cent.



  5. 5. Vertical transmission can occur with caesarean section if there has been prolonged rupture of membranes, and rarely with intact membranes, indicating either a transmembrane or a transplacental transmission.



Diagnosis of Neonatal Chlamydia Infection




  1. 1. Clinical suspicion.



  2. 2. NAAT should be effective in the diagnosis of neonatal infections.



  3. 3. In conjunctivitis, specimens should be obtained from the everted eyelid using a dacron-tipped swab or the swab specified by the manufacturer’s test kit.



Treatment of Neonatal Chlamydia Infection


Oral erythromycin for two weeks is the recommended treatment of neonatal chlamydia or pneumonia, and additional topical therapy is unnecessary. A repeat oral course of antibiotics may be required in approximately 20–30 per cent of infants.18



Pathophysiology of Female Genital Chlamydia trachomatis Infection


In the female, C. trachomatis infection affects the cervix, urethra, salpinges and the uterus. Epithelial cells, through a release of cytokines and interferons, initially respond to infection by a neutrophilic infiltration, followed by lymphocytes, macrophages, plasma cells and eosinophilic invasion.19


Chlamydial organisms infection causes a humoral cell response, with the production of circulatory immunoglobulin M (IgM), immunoglobulin A (IgA) and IgG antibodies.19



Infectivity of Chlamydia trachomatis




  • The bacterium is usually spread to sexual partners through all forms of sexual activity via unprotected vaginal, oral or anal sexual intercourse



  • The incubation period is usually 7–21 days



  • An infected male has a 25 per cent chance per sexual encounter of transmitting the infection



  • Approximately 50 per cent of infected males and 80 per cent of infected females are asymptomatic20



  • In women with PID, 5–10 per cent develop perihepatitis (i.e. Fitz-Hugh–Curtis syndrome)



  • Fitz-Hugh–Curtis syndrome is characterised by acute right upper abdominal pain; clinical diagnosis is apparent if it is associated with other chlamydia signs or symptoms


If untreated, chlamydial infection may persist for years.



Diagnosis




  1. 1. Nucleic acid amplification test




    • NAAT is a molecular technique to detect the genetic material (nucleic acid) of a particular pathogen (virus or bacterium) in a blood, other body-fluid or tissue specimen. It yields rapid results and accurate diagnosis.



    • NAATs can be performed on different body fluids (endocervical, urethral, vaginal, pharyngeal, rectal or first-void urine (FVU) samples).



    • The accuracy of NAATs on urine samples is nearly identical to that of samples obtained directly from the cervix or urethra. [EL 1]



    • Vaginal, introital or vulvar swabs from women are excellent specimens and can be self-obtained for the detection of C. trachomatis by NAAT tests. For self-taking of vaginal swabs, the swab is inserted about 5 cm into the vagina and rotated gently for 10–30 seconds.



    • For FVU testing, the first 10–30 mL of urine is collected for testing. Specimens should ideally be obtained between two and six hours after the last micturition. It is not necessary, and may not be advantageous, to obtain the first urine specimen passed in the morning.



    • The Centers for Disease Control (CDC) currently recommend using NAAT as the standard laboratory test, as it allows prompt treatment and therefore reduction of disease transmission. [EL 1]




  2. 2. Serum specimens are not recommended for the diagnosis of acute chlamydia infections as the immune responses that can be detected are usually short-lived or are present due to past infections. The only two exceptions where serology may be helpful are chlamydial neonatal pneumonia (high IgM) or chlamydial tubal factor infertility (high IgG). A clotted specimen should be submitted.21


    Fresh samples are preferred, but frozen material (−70°C) is acceptable.



  3. 3. Cytological testing is relatively insensitive when diagnosing adult conjunctival and genital tract infections.



  4. 4. Isolation in cell culture and microbiological examination




    • Most, if not all, chlamydiae appear to be able to grow in cell culture. This is the only method to confirm the presence of viable bacteria because other diagnostic methods (antigen/antibody testing or the NAAT) can show positive results in the absence of viable infectious particles.



    • Either immunofluorescence or a fluorescent microscope is required.



    • It can take a few days for the bacteria to multiply to sufficient numbers to be identified by culture.



    • Vaginal swabs are the preferred specimen for screening women for genital chlamydia infection.



    • Rectal and oropharyngeal specimens are preferred for those at risk of extragenital tract infections.




Differential Diagnosis


Differential diagnosis of Chlamydia trachomatis infection includes a long list of diseases, which may produce similar symptoms:




  • Gonorrhoea (although co-infection is relatively common)



  • Herpes simplex



  • Trichomonas vaginalis infection



  • Urinary tract infection



  • Bacterial vaginosis



  • Candidiasis



  • Urethral/vaginal foreign body



  • A periurethral abscess may also cause similar symptoms

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Sep 30, 2020 | Posted by in GYNECOLOGY | Comments Off on Chapter 17 – Genital Chlamydia trachomatis and Bacterial Vaginosis

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