Chlamydial serovars, tissue tropism and clinical diseases. Acute and chronic pathologies occur in men, women and newborns following CT infections. Serovars A to C have tropism for ocular epithelium, causing from acute conjunctivitis to infectious blindness or trachoma. Serovars D to K infect epithelial cells of the genitourinary system, generating a broad range of acute and chronic pathologies that damage reproductive tissue and may infect newborns during labor. Serovars L1–3 cause lymphogranuloma venereum. Several autoimmune diseases are associated to diverse CT strains.
Chlamydia trachomatis (CT) is the most common agent of bacterial sexually transmitted infections, both in developed and developing countries. It clearly constitutes a major burden on public health. Screening programs and current research are mainly focused on decreasing the high incidence of chlamydial infections as well as their associated morbidity.
- Chlamydia trachomatis
- intracellular pathogens
- bacterial sexually transmitted infections
- tubal obstruction
- female infertility
In this chapter, we briefly present the current knowledge about the cell biology of the bacteria, reviewing the mechanisms of establishment of CT intracellular niche, the inducers of persistent infections, and the pathogen factors that may be involved in the damage of female reproductive tract. Then, we analyze the host factors that may contribute to the development of infertility, mainly immune response and genetic predisposition, hormonal status, and sexual behavior. Undiagnosed and untreated infections, repeat and persistent infections, and coinfections are likely responsible for the detrimental sequelae on woman fertility of CT pathogenesis.
This chapter specially focuses on the consequences of chronic diseases after CT infections, mainly pelvic inflammatory disease, tubal infertility, and adverse pregnancy outcome, which are of therapeutic interest in the reproduction field.
2. The bacteria: Intracellular life cycle,
Chlamydia trachomatisserovars and virulence factors
2.1. Chlamydial developmental cycle and intracellular niche
CT is a highly evolved pathogen that has a reduced genome, first sequenced by Stephens and collaborators in 1998. Its chromosome consists of approximately one million base pairs and encodes for up to 600 proteins . Analysis of chlamydial genes reveals that this bacterium heavily depends on host cell for nutrition and replication, indicating a complex evolution for adaptation to an obligate intracellular lifestyle.
CT has tropism for genital mucosal epithelium, which promotes its own uptake into non-phagocytic cells. Chlamydial infection and propagation rely upon a unique biphasic life cycle that begins by contact of infectious, environmentally resistant, elementary bodies (EBs) with the apical surface of the epithelial cell. Several mechanisms are involved in the invasion of host cell, likely parasite-specified phagocytosis and receptor-mediated endocytosis . Multiple receptors have been proposed to mediate the interaction between the EB and the host cell, among them, the mannose receptor, the mannose 6-phosphate receptor, and the estrogen receptor . Other host molecules such as heparan sulfate proteoglycans [6,7], and protein disulfide isomerase also participate in EB binding to the eukaryotic cells . Concomitantly, multiple bacterial adhesins and ligands such as glycosaminoglycan , the major outer membrane protein (MOMP) , OmcB , and PmpD  facilitate EB attachment to host cells. Translocated actin-recruiting phosphoprotein (TARP) is a bacterial protein that nucleates actin and promotes host cell cytoskeleton remodeling to force bacterium uptake [13–15].
The infectious EBs enter the host cell in membrane-bound vesicles that travel toward the perinucleus and fuse to form a single vacuole termed the inclusion. Once inside this modified phagosome, EBs differentiate into metabolically active but non-infectious reticulate bodies (RBs) that are the replicative bacterial forms. RBs asynchronously multiply by binary fission within the confines of the growing inclusion. After numerous rounds of replication, RBs re-differentiate back into infectious EBs to be ready for spreading to adjacent cells [16,17]. The ability of CT to cycle between resting and replicating organisms accounts for a drawback in the eradication of this intracellular pathogen. Finally, the infectious bacteria are released by two independent mechanisms, the host cell lysis, or the extrusion of the inclusion . A scheme of chlamydial developmental life cycle is shown in Figure 1.
In response to stress, CT enters into a low replicative viable state that is termed “persistent or aberrant bacterial form”, which is able to resume normal replication as soon as conditions are again favorable. Among the inducers of the persistent bacterial state stand the sphingolipid deprivation and tryptophan lack, the presence of interferon gamma (IFN-γ), or certain antibiotics such as penicillin. The evasion strategy has been linked to the capacity of these bacteria to cause latent and chronic infections. Thus, the onset of the infection is generally not detected and re-infection may occur, especially when infected couples are involved. Furthermore, the fact that CT clearance is rarely followed up, combined with the ability of this pathogen to persist, contributes to the occurrence of long-term infections .
Undoubtedly, an essential issue to chlamydial growth and development is the establishment of its intracellular niche. Early chlamydial gene expression is required to inclusion generation, to avoid immune system surveillance, and to hijack host cell functions . These bacteria actively modify the inclusion membrane by exclusion or recruitment of selected host proteins, mainly Rab proteins, the master controllers of intracellular traffic [16,21]. Increasing evidence points out that the invading bacteria subvert trafficking not only to circumvent the lysosomal degradative route but also to facilitate the delivery of host nutrients to the growing inclusion [17,22]. As soon as the chlamydial inclusion is formed, it dissociates from the classical phagocytic pathway and barely interacts with endocytic vesicles . Instead, chlamydial inclusion intersects Golgi-derived vesicles [24–27], multivesicular bodies , and lipid droplets [29,30]. By this strategy, these bacteria take over the infected cell for sphingomyelin, cholesterol, and neutral lipid acquisition like pirates [31–34]. In addition, CTs possess other mechanisms, such as transporter molecules, finely adapted to acquire amino acids, nucleotides, and energy from the host cell [22,35–38]. At present, the strategies developed by CTs to re-route intracellular trafficking and to co-opt host cell functions for their benefit are being actively studied.
2.2. Bacterial genotypes and virulence factors
Different strains of CT have been described based on genome sequencing and the antigenic properties of the major outer membrane protein (MOMP) . There are more than 20 distinct serovars (serologically variant strains) of CT currently identified, on the basis of monoclonal antibody-based typing assays [40–42]. In general, CTs have been grouped into three main pathobiotypes: ocular infections (serovars A to C), sexually transmitted diseases (D to K), and lymphogranuloma venereum (L1 to L3). Serovars A, B, and C have tropism for the ocular epithelium, causing from acute conjunctivitis to trachoma, a serious eye disease endemic in Africa and Asia that is characterized by chronic conjunctivitis and can lead to infectious blindness. Serovars D through K have emerged as the major causing agents of sexually transmitted diseases. They preferentially infect squamocolumnar epithelial cells of female reproductive system and the male genitourinary tract. E and D serovars are isolated from genital tract infections with the most frequency worldwide. Occasionally, they cause conjunctivitis or pneumonia in newborns infected during labor. Serovars L1 to L3 are responsible for a systemic illness, the lymphogranuloma venereum that is associated with genital ulcer disease in tropical countries [43,44] (Table 1).
On the other hand, CT gene polymorphisms determine distinct antigenic challenge to the immune system . Certain bacterial polymorphisms may induce an altered immune response . In consequence, they are able to cause immunological disorders, especially in susceptible individuals. Chlamydial infections often precede the initiation of autoimmune diseases, and frequently, these bacteria are found within autoimmune lesions. Bacterial proteins similar to host self-proteins might be the underlying cause of diverse autoimmune diseases [51,52]. This molecular mimicry may elicit an immune response to both self and microbial proteins. Chlamydial heat shock protein 60, DNA primase, and OmcB proteins represent the strongest cases for molecular mimicry . The most frequent autoimmune diseases connected to chlamydial infections are intestinal inflammatory pathologies and rheumatic or connective-tissue diseases [54,55]. Further research is required to unravel the molecular machinery involved in the complex pathogen-host cell interaction.
|D–K||Newborn||Ophthalmia neonatorum||Neonatal pneumonia|
Pelvic inflammatory disease
Premature rupture of membranes
|L1–3||Both sexes||Lymphogranuloma venereum|
|Different serovars and bacterial polymorphism||Both sexes||Autoimmune diseases|
Inflammatory bowel disease
Several putative virulence factors have been postulated, including the polymorphic outer membrane autotransporter family of proteins (pmp), type III secretion system (TTSS) effectors, a large cytotoxin, and stress response proteins may contribute to increase the CT-associated pathogenicity. Pmp proteins are strongly immunogenic and trigger pro-inflammatory cytokine responses . Chlamydial TTSS effectors mediate the interaction with the host as they are injected to the cytoplasm and alter host cell functioning [57–59]. Important TTSS effectors are the inclusion (Inc) proteins that are bacterial proteins present at the inclusion membrane. For instance, IncA promotes the fusion of individual CT-containing vesicles to form a single inclusion [60,61]. Natural IncA bacterial mutants are associated with reduced virulence . Another TTSS effector is TARP, mentioned in the previous section, as a bacterial protein that favors CT internalization via an actin recruiting mechanism [34,63]. Additionally, a chlamydial cytotoxin glycosylates the eukaryotic protein Rac1, and thereby induces actin reorganization and promotes the invasion of host cell [64,65]. Chlamydial glycolipid exoantigens  and the lipopolysaccharide  may constitute additional virulence factors. Other proteins encoded by the cryptic plasmid or related to the ability of the bacteria to survive under stressful metabolic conditions such as iron or tryptophan deprivation are thought to increase virulence and pathogenicity [68,69]. Chlamydial stress proteins, GroEL and GroES, may activate toll-like receptors and trigger a potent inflammatory response, injuring host reproductive tissues [70–73].
In addition to CT serovars and virulence molecules, other bacterial factors may be involved in the pathogenicity and chlamydial infection outcome, such as the pathogen load, route of infection, bacterial ability to enter persistent state, ascension capacity and strength to colonize genital upper tract, resistance to antibiotic treatment, and so on. Further studies are needed to determine the contribution of each bacterial factor to the development of severe damage on the female reproductive system.
3. The host: Immunological and genetic factors, age and hormonal status, and sexual behavior
3.1. Immunological and genetic factors
An important issue that contributes to CT pathogenesis is its remarkable ability to avoid the host immune system. Several strategies are displayed by these bacteria to prevent immune degradation, such as its intracellular lifestyle, its ability to escape from phagolysosomal pathway, its resistance to interferon gamma (IFN-γ), among others lesser known bacterial molecules. Actually, host immune response has opposite results on chlamydial infection outcome. A low immune response generates a suitable environment for pathogen colonization, while a strong immune response could lead to excessive inflammation and tissue damage. Pathogens own characteristics in conjunction with host genetic susceptibility are important in determining the severity of the illness.
At the site of invasion, an intense inflammation occurs, attracting different types of cells, such as macrophages, neutrophils, T and B lymphocytes, natural killers, and dendritic cells. Locally, there is an increased production of reactive oxygen species (ROS) that produces oxidative DNA damage, lipid peroxidation, energy depletion, modulation of gene expression, and proteins synthesis. Oxidative stress provokes pathologic changes that harm reproductive tissues. In addition, a broad collection of pro- and anti-inflammatory cytokines are released including IFN-γ, tumor necrosis factor (TNF-α), interleukin (IL) IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-22, vascular endothelial growth factor (VEGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and lactoferrin. These mediators trigger cellular inflammatory responses that mediate direct damage to the tissues [74,75]. Most of them are involved in the pathophysiology of tubal infertility, birth defects, and miscarriage .
In addition to the inflammatory response, CT infection evokes vigorous local and systemic humoral and cell-mediated immune responses. Several CT-specific antibodies, IgG isotype rather than secretory IgA, are found in circulation and in the cervicovaginal fluid of the female genital tract. These antibodies can neutralize chlamydial antigens; nevertheless, they do not assure resolution of the infection. Antibodies toward the bacterial MOMP protein are prevalent in primary chlamydial infections, whereas antibodies against CT-hsp10 and hsp60 are present in recurrent or persistent infections and correlate with severe sequelae such as tubal infertility, ectopic pregnancy, and PID [77–79]. Regarding the cell-mediated immune response, the T-helper lymphocytes type 1 (Th1) secrete IFN-γ, IL-2, and IL-12 and play a role in the resolution of infection [80,81]. On the other hand, the T-helper lymphocytes type 2 (Th2), which support the humoral immune response, produces IL-4, IL-5, IL-6, and IL-10 and participates in the developing tubal scarring . The inflammatory response occurs, at the same extent, in both initial and repeat infections, whereas T-cell responses are predominant in the latter ones [80,83].
Actually, host immune response is considered as one of the most important determinants in chlamydial infection outcome. A delicate balance between pro- and anti-inflammatory cytokines is needed to clear infection, avoiding tissue injuring. At this point, host genetic predisposition is a major player of pathology and CT-related infertility development .
Host genetic polymorphisms may encode aberrant or dysfunctional toll-like receptors (TLR) and nucleotide-binding oligomerization domain proteins (NOD) that do not appropriately recognize CT. These individuals have an impaired bacterial clearance and a high risk to develop an aberrant immune response, favoring CT persistence [85–88]. Identifying host genetic factors and bacterial virulence factors involved in immunoevasion and immunopathology remains a major priority in research for preventing chlamydial infection and its sequelae. Furthermore, the understanding of local innate and adaptive immune responses and their actors along the genital tract will be crucial for designing new therapeutic approaches and for developing a protective vaccine.
3.2. Age and hormonal status
CT preferentially targets young women at reproductive age. It has been reported that the highest incidence occurs in women between 16 to 24 years . Therefore, the impact on female reproductive health is very important. Notwithstanding younger women are at higher risk of contracting a chlamydial infection, the rates of developing PID increase with age, being more frequent in the 30 to 40 decade . After menopause, the frequency of chlamydial infections decreases substantially .
Accordingly, estrogen and progesterone are important for the establishment of chlamydial infection. Furthermore, estrogen receptors have been involved in the internalization of CT [92,93]. Sex hormones affect the clinical outcome of chlamydial infections; thus, follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), progesterone (P4), and prolactin (PRL) are involved not only in the establishment of chlamydial infection but also in the development of sequelae on reproductive tissue [94,95]. Additionally, oral contraceptive use was found to be a risk factor for CT infection. Several studies have attempted to elucidate the relation between the hormonal status at the time of infection and its contribution to tubal occlusion in genital chlamydial infection. Unfortunately, the role of sex steroids in infection outcome is far from being fully understood. Sex hormones have been shown to modulate immune responses and to have antioxidant effects in the female genital tract [96–98]. However, the mechanisms by which sex hormones may benefit or impair the colonization of genital tissues by pathogenic microorganisms should be further investigated.
3.3. Sexual behavior and other host factors
Sexual initiation at young age and a higher number of sexual partners are associated with increased risk of CT infection . In a similar manner, having sex without protection favors CT contagion. This sexual behavior is also associated with higher incidence of sexually transmitted pathogens such as
In general, multiple sexual partners and unsafe intercourse increase the risk of CT recurrent infections and coinfection with other sexually transmitted pathogens. Thereby, the high chance to suffer repeat and chronic infections that target women reproductive tissue raises the infertility-associated pathologies.
4. Pathogen-host interplay: Establishment of latent, repeat, and persistent infections and coinfections
CT survival and replication heavily hinge on host cells. In fact, CT has evolved in relationship with human cells. However, little is known about the molecular basis of CT interaction with host epithelia and immune system. An increasing number of bacterial and host factors interplay for the establishment of chlamydial infection and determine the pathologic profile and clinical disease outcome. A simple scheme is shown in Figure 2 summarizing the main CT and host factors that jointly with environmental factors and the failure in diagnosis and treatment, lead to unsolved, latent, and long-term chlamydial infections.
Microbiome (microbial flora present at the genital tract) and the presence of other sexually transmitted pathogens may be important for the colonization of reproductive tissue and the establishment of chlamydial infection. The presence of lactobacilli in the vagina confers protection against the acquisition of chlamydial infection . In contrast, indole-generating bacteria present in the microbiome or bacterial vaginosis allow CT to synthesize tryptophan, and consequently, to avoid the anti-chlamydial activity of IFN-γ [45,65]. Coinfections are more frequent in vaginosis and women with high-risk sexual behavior . Clearly, coinfections exacerbate host immune response and inflammation; therefore, they favor scarring and sequelae on female reproductive system and increase the likelihood of tubal infertility.
The worst scenarios involve silent and latent infections that underline chronic persistent chlamydial infection and frequent re-infections . Chlamydial infections may persist in the female upper genital tract for months in the absence of treatment. They are often asymptomatic or alternate quiescent stages with periods of clinical manifestations . Actually, chronic chlamydial infections may be because of the reactivation of asymptomatic latently infected deep-seated cells. The presence of aberrant bacterial forms responsible for chlamydial persistence constitutes a long-time challenge to the immune system. Host immunopathological response can damage the fallopian tube and generate female infertility [65,92].
Reinfections, persistent infections, and treatment failure account for repeat infections that represent a substantial proportion of the chlamydial infections detected annually . Repeat infection is not the sole determinant of severe genital tract pathology and sequelae. However, repeat infection increases the risk of developing tubal obstruction and female infertility .
Increasing evidence indicates that long-term persistence of viable aberrant chlamydial organisms within host cells is associated with inflammatory and autoimmune diseases in extragenital tissues.
In definitive, the pathogen-host interplay and the concurrency of exogenous factors appear to be related to CT-induced immunopathology. In spite of the substantial worldwide impact of chlamydial disease, the bacterial and host factors that result in infertility are still not clear. Current efforts are focused on discovering what CT is doing to the host cells to prevent sequelae and undesired consequences of infection.
5. Mechanisms of pathogenicity and clinical course
CT infects both sexes; however, chlamydial infections constitute primarily a female health issue since the consequences are more damaging to the reproductive tissue in women than in men. In males, CT can infect urethra, epididymis, prostate, seminal vesicles, and testis. Usually, chlamydial infections are symptomatic, less frequent, and more easily eradicated in men than in women. Nevertheless, chlamydial infection in the male genitourinary tract might induce severe damage to seminiferous tubules, spermatogenesis, and sperm cells morphology that can result in impaired male fertility .
Here, we focus on chlamydial infections occurring in women. In first world countries, 3 to 5% of women younger than 30 years old will be infected by CT at any point in time [90,108]. And, in over 70% of the cases, CT infection of the female genitourinary tract is asymptomatic, spoiling the prevalence or incidence rates. Consequently, it is difficult to assess the incidence of sequelae, mainly PID, tubal obstruction, and female infertility, attributable to genital CT infection.
In women, CT is the major cause of mucopurulent cervicitis (MPC) and PID. Other manifestations of chlamydial infections are vaginitis, urethritis, salpingitis, endometritis, tubo-ovarian abscess, pelvic peritonitis, periappendicitis, and perihepatitis. The symptoms more frequently reported consist of abdominal pain, dysuria, vaginal itching, and abnormal vaginal discharge. However, the most important feature of chlamydial infection in the female genital tract is the occurrence of asymptomatic infection that remains subclinical for long periods in a high rate [109,110]. Asymptomatic ascending bacteria from the cervix may produce two groups of pathologies: (i) PID-associated complications such as chronic pelvic pain, tubal obstruction, and female infertility [111,112] and (ii) adverse pregnancy outcomes such as ectopic pregnancy, miscarriage, premature rupture of membranes, chrioamnionitis, preterm birth, stillbirths, and puerperal and neonatal infections [113–115].
General consensus in the medical community agrees that chlamydial PID is the most common preventable cause of tubal infertility and adverse pregnancy outcome . However, the lack of systematic detection of the bacteria weakens these estimations, usually performed by analysis of a reduced number of cases. Approximately 20% of women with chlamydial lower genital tract infection will develop PID, 4% chronic pelvic pain, 3% tubal infertility, and 2% adverse pregnancy outcome . In developing countries, the incidence and prevalence of CT infections and their harmful consequences on female reproductive tissue are not accurately known since CT infection is not routinely screened.
There is conclusive evidence that women who have suffered PID have higher risk to develop tubal infertility. A study demonstrated that 16.5% of women with abnormal laparoscopic findings likely resulting of acute PID failed to conceive, in comparison to 2.7% in control women; 10.8% developed tubal infertility, and 9.1% went through ectopic pregnancy. Therefore, PID increases the probability of permanent damage on female reproductive system. CT is the most common causing agent of PID; however, a drawback of this analysis is the lack of the identification of the infectious agent underlying the PID. Several randomized controlled trials to assess the value of CT screening found it helpful to reduce the incidence of PID among infected women [116–118]. The chance to develop tubal infertility after a single episode of PID is around 10% . Furthermore, each episode of PID doubled the risk of tubal damage  independent of whether the infection was asymptomatic or not.
One of the most serious sequelae of PID and persistent chlamydial infections is the fibrosis and scarring obstruction of the fallopian tubes that leads to tubal infertility. However, the risk of tubal infertility due to CT infections is lower than PID incidence . The proportion of tubal infertility among all causes of infertility varies from 40% in first-world countries to 85% in developing countries . Undiagnosed and untreated chlamydial infections usually evolve to long-term persistent infections, in which chlamydial antigens chronically stimulate the host immune system. Abnormal humoral and cell-mediated immune responses and severe inflammation have been implicated in the development of immunopathological damage of fallopian tubes. Thus, the interaction between CT and the host becomes relevant for the illness outcome. However, the exact pathologic mechanism of CT-induced tubal damage and tubal infertility has not been elucidated yet.
In addition, acute and chronic maternal chlamydial infections constitute a significant risk factor for adverse pregnancy outcomes and newborns contagion. Untreated and persistent infections are strongly associated with ectopic pregnancy, which is the tubal development of the embryo and constitute the main cause of maternal mortality in the first trimester of pregnancy in developing countries. In addition, miscarriage, chrioamnionitis, low birth weight, stillbirth, premature rupture of membranes, and preterm birth are frequent pathological consequences of chlamydial infections [51,113,114]. Several mechanisms may contribute to the development of these pathologies, including direct fetal infection, placental damage, and severe puerperal maternal illness [120–124]. Nevertheless, the exact nature of chlamydial infection pathogenesis during pregnancy remains unexplained.
CT infections can also be vertically transmitted to newborns during labor, resulting in chlamydial conjunctivitis and/or pneumonia, which may possibly involve similar pathogenesis mechanisms to those occurring in the female genital tract.
Controversial reports point out CT as a risk factor for cervical carcinoma, independent of human papillomavirus . It has been shown that CT interferes with multiple proapoptotic pathways to guarantee survival within host cells [125,126]. In addition, CT activates prosurvival signaling pathways for bacterial nutrient acquisition, expression of antiapoptotic factors, and synthesis of proinflammatory cytokines [127,128]. On the other hand, CT interferes with chromosome segregation and cytokinesis. In consequence, multinucleated cells and cells with aberrant number of chromosomes are often observed in cell cultures infected with CT . Taken together, these findings suggest that persistent chlamydial infections might play a role in the development of cervical neoplasia. Further research is needed to shed light to this issue.
The high prevalence and incidence estimates worldwide, in conjunction to the diversity of clinical entities and long-term consequences of chlamydial infections, propel further research of the bacterial and host factors involved in the pathogenesis and damage to the reproductive system.
6. Important challenges: Prevention, diagnosis, and treatment of chlamydial infections
The widespread incidence and prevalence of sexually transmitted infections, especially among young population, made them a priority public-health concern worldwide. Screening, control programmes, and education in sexual behavioral aspects and contraception are fundamental for the prevention of chlamydial infections and their long-term sequelae, mainly PID and tubal infertility.
Routine screening allows the identification of asymptomatic carriers of CT and contributes to the early detection of chlamydial infections. Appropriated diagnostic services are required to obtain reliable results. The most confident tests for the detection of CT involve nucleid acid amplification techniques that are not available in all laboratories, especially in third-world countries. Nucleic acid amplification tests are more sensitive than culture or antigen tests. Improvement in molecular diagnostics will lead to improvement in treatment and prevention of damage to reproductive tissues. It has been shown that screening is cost-effective even in low prevalence populations, due to the high costs of treatment of complications resulting from undiagnosed and untreated chlamydial infections . The implement of additional targeted screening of women at risk will contribute to reduce the CT-associated infertility.
Additionally, clinicians should be aware about the latest therapeutic management of chlamydial cervicitis and PID. Different antibiotics such as azithromycin, doxycycline, ofloxacin, erythromycin, and amoxicillin may be useful for treating genital chlamydial infections . The antibiotic selection depends on the characteristics of the drug itself like pharmacokinetics, half-life, and bioavailability, concentration in mucous membranes and genital tissues, development of gastrointestinal tract side effects, safe use in pregnancy, as well as, the characteristics of the host and the clinical course of chlamydial infection. The effectiveness of therapy relies on timely treating sex partners and to abstain from sexual intercourse until completing the whole antibiotic scheme.
Unceasing efforts are conducted for the development of a chlamydial vaccine. Nevertheless, until now, no effective chlamydial vaccines are available. The knowledge of bacterial factors involved in pathogenicity will help in addressing optimal vaccine design that prevents not only chlamydial infection but also progression to infertility.
The authors acknowledge CONICET (PIP), Foncyt (PICT 2116) and UNCuyo grants to M.T.D. for their support in research. They apologize to those investigators whose work could not be cited because of space constraints.
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