ADVERSE EFFECTS OF GENITO-URINARY INFECTIONS

THE ADVERSE EFFECTS OF GENITO-URINARY INFECTIONS (BOOKLET)
With a special emphasis on Chlamydia Trachomatis
A review from the Literature by Tuula E. Tuormaa for FORESIGHT,
the Association for the Promotion of Preconceptual Care.
First published in: Journal of Nutritional Medicine (1994)4, 351-361

Introduction
The attitude to sex in Western societies has changed remarkably since the early 1960's, when premarital sexual experiences became gradually acceptable. Now thirty years later, an active and satisfying sex life, whether within marriage or outside it, is considered almost an essential human right. Unfortunately, a direct consequence of this sexual freedom has been an alarming spread of sexually transmitted diseases, both gonococcal and non-gonococcal, the latter group consisting of all sexually transmitted infections from which gonococci cannot be cultured or identified in smears (1).

The true epidemiology of sexually transmitted diseases in the U.K. is difficult to establish and under-reporting is widespread, as most available figures in the U.K. exclude patients who are treated by their own general practitioner as well as patients in the armed forces (2).

Chlamydia Trachomatis

The classical venereal diseases, such as syphilis and gonorrhoea, are still reasonably readily recognised, diagnosed and treated. However, recent epidemiologic research has revealed that the other group of sexually-transmitted infectious agents, i.e. non-gonococcal, are now much more common, as well as much more wide spread, than the classical venereal diseases. According to a recent survey by the Royal College of Physicians' Committee on Genito-Urinary Medicine, probably now the most common sexually-transmitted disease in the Western world is caused by a bacterium Chlamydia trachomatis (3). 1979 UK annual figures estimated the incidence of sexually transmitted infections as being about half a million new cases, of which 40-50% were thought to be chlamydial in origin (4). More recent surveys suggest that of approximately 100,000 reported cases of non-gonococcal urethritis (NGU) in the UK each year, about 35-60% are caused by Chlamydia trachomatis (5,6).

The actual epidemiology of chlamydial infection carriers is impossible to determine because as many as 70% of females infected may be essentially without symptoms, although mild symptoms such as slight vaginal discharge and occasional mild abdominal pain may be present (7,8). Furthermore it has been estimated that up to 50% of males infected with Chlamydia trachomatis could be asymptomatic (9). This extremely high percentage of both male and female symptomless carriers obviously increases the potential transmission and makes Chlamydia trachomatis currently the most insidious of all sexually-transmitted infections. Even though the true epidemiology of chlamydial infections is not known, several current research studies have shown that the incidence of Chlamydia trachomatis infections seems to range from 8% to 40%, depending on the population studied, with a typical median of 15% (4,5,10-12); it is particularly on the increase among adolescents (13,14). In fact, it has been found that the statistical risk markers for chlamydial infections have been remarkably uniform; young age often combined with unmarried status. Other risk factors have been found to be: anatomic (ectopy), microbiological (concurrent gonorrhoea), hormonal (oral contraceptive use) and behavioural (number of sex partners). Lower socio-economic status also seems to predict higher rates (12). In the United States a recent survey put the number of individuals infected by Chlamydia trachomatis as more than 4 million, of which approximately 2,600,000 were females, 1,800,000 males, including 250,000 infants (15).

Chlamydial infection in females
Chlamydial infection produces far less severe symptoms than gonorrhoea, and because of these deceptively mild symptoms the infection goes undetected for a very long time with a minimum of patients awareness until secondary or tertiary problems arise. In females, Chlamydia trachomatis infects first the cervix causing cervicitis (16-20), spreading canalicularly to the endometrium thus leading to endometritis (21). The really serious damage occurs when it is left untreated and the infection is allowed to ascend to the fallopian tubes where it manifests itself as an acute salpingitis (22-33) and/or pelvic inflammatory disease (34-40).

Chlamydial infection and infertility
Tubal damage caused by acute salpingitis and/or pelvic inflammatory disease is the most common cause of female infertility (41). Because of its 'smouldering' nature, Chlamydia trachomatis has been found to play a key role in both of these conditions (12). Recent research suggests that up to 66% of cases of acute salpingitis and over 30% of pelvic inflammatory infections may be chlamydial in origin (26). In addition, a large number of investigations from several countries, despite variations of design, have uniformly found clear serological evidence of a link between chlamydia infection and tubal infertility (42-67). Besides causing infertility, Chlamydia trachomatis has also been found to be directly responsible for ectopic pregnancy, (68-74) prematurity, perinatal mortality and spontaneous abortions (75,76).

Chlamydial infections in neonates and infants
Several published studies have established that the prevalence of chlamydial infections found in pregnant women ranges from 2% to 25% depending on the population screened (76-83). Furthermore, it has been shown that least 50-70% of infants born to mothers with Chlamydia infection will develop chlamydial infection at some site during delivery (81-88).

Clinical infections in infants directly associated with Chlamydia trachomatis
Inclusion conjunctivitis: This is acquired by the newborn during delivery by a direct eye contact with infected maternal cervical discharge (82, 83, 89-93). It has been estimated that up to 35-50% thus exposed will develop chlamydial ocular infection (82,83,86). Although inclusion conjunctivitis is generally regarded as a relatively benign disease there is now accumulating evidence that in some cases it may progress to neovascularization (pannus) and conjunctival scarring, signs usually associated with a classic trachoma (94-96).

Pneumonitis: The first case of pneumonitis associated with Chlamydia trachomatis was described in 1975 by Schachter et al. (97). Subsequently, several researchers have found direct evidence of a link between maternal chlamydial infection and consequent infant pneumonitis, characterised by a dry, hacking cough, chronic pulmonary infiltrates and an afebrile course (83,98-105). It has also been suggested that infant chlamydial pneumonitis may result later on in chronic respiratory sequelae (106).

Otitis media: In infants Chlamydia trachomatis has also been isolated in the middle ear (107) and subsequently found to be a direct cause of acute otitis media (86,88,108,109).

Gastro-enteritis: Rectal infections with Chlamydia trachomatis in exposed infants have been found to be relatively common (87). Therefore Chlamydia trachomatis has been suggested as the potential cause for gastro-enteritis (110).

Unspecified viral disease: Infants born to chlamydia culture-positive mothers have also been found to at be at a significantly greater risk of suffering from unspecified viral diseases than infants born to women with negative cultures (88).

Apart from inclusion conjunctivitis, pneumonitis, otitis media, gastro-enteritis and unspecified viral diseases, conditions such as rhinitis, naso-pharyngitis, proctitis, vulvitis and failure to thrive have been found to occur more often in infants born through a Chlamydia-infected birth canal than in infants born to uninfected mothers (83,88,111).

Chlamydial infection in Males
Several research studies have shown that Chlamydia infection is directly responsible for both epididymitis and non-gonococcal urethritis (112-124). In fact, it has been estimated that between 30-50% of these above mentioned conditions are thus caused (83,120).

Seventy-one infertile men were studied at the Institute of Biomedical Sciences, University of Tampere, Finland, for the presence of leucocytosis, and for the levels of acid phosphatase activity and Chlamydia trachomatis the immunoglobulin A of (IgA) class, using a novel method of solid-phase radioimmunoassay. The findings were compared with those of 56 fertile men. Chlamydial IgA antibodies were found in the semen of 51.1% of infertile men compared to 23.2% of fertile men. It was concluded that Chlamydia trachomatis, besides being a common cause for prostitis, can also affect fertility (125).

Other Bacterial Infections

Besides Chlamydia trachomatis and Neisseria gonorrhoea there are other bacterial agents which have been found to be involved in both maternal and neo-natal infections. Group-B streptococci are considered to be the most prevalent and have been isolated from 5-25% of asymptomatic females. The presence of group-B streptococci has been associated with endometritis, amnionitis, neonatal sepsis and premature rupture of the membranes, and premature birth (126).

Viruses

The two most common viruses involved in maternal and neonatal infections are currently considered to be Cytomegalovirus and Herpesvirus hominis. Cytomegalovirus as a primary infection during pregnancy can cross the placenta and infect the foetus, frequently resulting in brain damage. Its more severe form may produce blindness, deafness, acute microcephaly, mental retardation, cerebral palsy and death. Currently, prenatal infections affect thousands of infants and 1-2% of them will have severe disease in early life and ensuing handicap. In the UK, it has been estimated that annually about 2800 infants are infected by the Cytomegalovirus and at least 500 infants suffer severe brain damage (4). Herpes virus hominis. If the mother has a primary attack at the time of delivery, this can result in the newborn suffering severe damage to the central nervous system, eyes, skin or liver (4).

Mycoplasmas

Studies of pregnant women have found that the frequency of cervical colonization with genital mycoplasmas ranges from 6% to 53% for Mycoplasma hominis, and from 35% to 93% for Ureaplasma urealyticum (127-131). A considerably higher incidence of spontaneous abortions, prematurity and neonatal morbidity and mortality has been reported among mothers with positive Mycoplasma cultures compared to mothers with negative cultures (132-134). Mycoplasmas have also been found to be a cause for infertility (135-136). There are other infectious agents which are frequently sexually-transmitted and which have been found to cause serious complications such as infertility, sterility and perinatal damage.

A recent survey (137) of 109 patients attending a London infertility clinic found that 69% of patients suffered from genito-urinary infections. The following infections were found in at least one patient:

Chlamydia
Heamolytic Streptococcus
Enterococcus
Heamolytic Influenza
Klebsiella B Streptococcus
Ureaplasma
Mycoplasma
Anaerobic bacteria
Candida Gardinerella
Streptococcus Millerii.
Eshericum Coli
Staphylococcus Aureas

Toxoplasmosis and Rubella can also contribute to neonatal morbidity and mortality. Although these conditions are comparatively rare, they can result in blindness, deafness, epilepsy and retardation of the offspring.

Summary

The radical changes in the attitude to sex and sexual behaviour have coincided with a dramatic rise in sexually transmitted infections. Whilst classical venereal diseases such as syphilis and gonorrhoea are in decline due to early detection and treatment, their place has now been taken by other groups of infectious agents, the most prevalent of which is Chlamydia trachomatis. In recent years, Chlamydia trachomatis has become increasingly recognised as a common human pathogen in many disciplines of medicine. In females it has been found to manifest as cervicitis, endometritis, acute salpingitis and pelvic inflammatory disease. It has also been found directly responsible for ectopic pregnancies, prematurity, perinatal mortality and spontaneous abortions. In addition Chlamydia trachomatis infection is directly implicated as one of the most common causes of infertility. In infants, chlamydial infection is associated with a myriad of clinical conditions including conjunctivitis, pneumonitis, otitis media, gastro enteritis, unspecified viral disease, rhinitis, naso-pharyngitis, proctitis, vulvitis and failure to thrive. In males, chlamydial infection is currently recognised as the leading cause of both epididymitis and urethritis, as well as contributing to male infertility or sub-fertility. Besides bacterial agents such as Chlamydia trachomatis, the spread of other infections (which are also frequently sexually- transmitted) caused by viruses and mycoplasmas, has grown during these last thirty years to near-epidemic proportions. Maternal mycoplasma infections have been associated with a high incidence of spontaneous abortions and prematurity, as well as neonatal morbidity and mortality. The presence of Cytomegalovirus in a mother is directly linked with severe mental handicap in the offspring.

Conclusion

As seen from the above, sexually transmitted infections are today a major and ever-expanding public health problem. They represent a vast social and economic drain in the form of hospital and drug treatments for acute salpingitis and pelvic inflammatory disease, consultations and laboratory tests for infertility investigations, infertility treatments, hospital admissions for infected infants, caring for the handicapped, etc. In short, the financial burden on society for treating these infected individuals is simply enormous. The vast amount of human suffering these infections entail is impossible to quantify. With the high prevalence of infections, the following measures should be taken in order to prevent the extremely serious consequences caused by genito-urinary infections:-

1. Because the majority of current genito-urinary infections seem to be asymptomatic, it is advisable that routine tests for these should be carried out alongside cervical smears. Routine testing should also be made available for males. In addition, contact tracing should be carried out whenever possible, to prevent further infections.

2. Serological tests for detecting genito-urinary infections should form a routine part of infertility investigations, as well as screening following miscarriage and! or premature birth (138,143). Greater access to chlamydial diagnosis would also be helpful in managing women with pelvic inflammatory disease who present to gynaecology departments (138,139), and in general for women who attend family planning clinics (140) and inner city general practices (141-143). Furthermore, pre-conceptual screening for all types of sexually transmitted infections should be advised and available on request.

3. Recent research has shown a significantly greater isolation rate of Chlamydia trachomatis infections in oral contraceptive users unrelated to promiscuity (144,145). It has been speculated that oral contraceptive users seem to suffer from a considerably higher prevalence of cervical ectopy than non-users (146), and it may be the ectopy which is associated with an increased Chlamydia risk because more columnar cells are exposed to the pathogen (19,147,148). These findings suggest that women using oral contraceptives should be screened for possible chlamydial infections more actively than non-users.

4. In recent years, it has become increasingly evident that asymptomatic carriage of Chlamydia trachomatis is associated with an extremely high risk of contracting post-abortal pelvic infections. Therefore, screening and treatment of positive cases prior to termination should be obligatory thus preventing severe post-abortal septic complications (149-154).

5. Tetracyclines are the drugs of choice in the treatment of chlamydial infection. In cases where tetracylines should not be prescribed, e.g. for pregnant and lactating women and for infants, erythromycin may be used as a satisfactory alternative. However, it should be noted that antibiotics not only destroy harmful bacteria but also useful bowel flora, which in turn may lead to monilial infections such as candida vaginitis (155-158). Some research has shown that the use of probiotics containing Lactobacillus acidophilus and/or bifidobacteria cultures can decrease the occurrence of monilial infections caused by antibiotic treatment (155-158). Furthermore, as all pharmacological agents, including antibiotics, are known to impair nutritional status, it would also always be advisable to include a balanced formula of vitamin/mineral supplementation with the antibiotic treatment (159). In addition, as all chronic bacterial and viral infections are known to decrease zinc concentration, a possible zinc deficiency should be investigated, and, where appropriate, zinc supplementation should be prescribed (160), particularly as lowered zinc status further decreases immunocompetence (161).

Such cost-effective preventive measures as mentioned above should now be regarded as an utmost necessity rather than a luxury.

Acknowledgements:
This study was supported by a grant from 'Foresight' The Association for the Promotion of Pre-conceptual Care.

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