Chlamydial and Gonococcal Genital Infections: A Narrative Review

Abstract

Sexually transmitted infections (STIs) constitute one of the leading causes of disease burden worldwide, leading to considerable morbidity, mortality, health expenditures, and stigma. Of note are the most common bacterial STIs, chlamydial and gonococcal infections, whose etiological agents are Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), respectively. Despite being usually asymptomatic, in some cases these infections can be associated with long-term severe complications, such as pelvic inflammatory disease, chronic pelvic pain, infertility, ectopic pregnancy, and increased risk of other STIs acquisition. As the symptoms, when present, are usually similar in both infections, and in most of the cases these infections co-occur, the dual-test strategy, searching for both pathogens, should be preferred. In line with this, herein we focus on the main aspects of CT and NG infections, the clinical symptoms as well as the appropriate state-of-the-art diagnostic tests and treatment. Cost-effective strategies for controlling CT and NG infections worldwide are addressed. The treatment for both infections is based on antibiotics. However, the continuing global rise in the incidence of these infections, concomitantly with the increased risk of antibiotics resistance, leads to difficulties in their control, particularly in the case of NG infections. We also discuss the potential mechanism of tumorigenesis related to CT infections. The molecular bases of CT and NG infections are addressed, as they should provide clues for control or eradication, through the development of new drugs and/or effective vaccines against these pathogens.

Keywords: Chlamydia trachomatis; Neisseria gonorrhoeae; diagnostic; infertility; prevention; screening; sexually transmitted infections; treatment; tumorigenesis.

Figure 1

Common clinical conditions associated with chlamydial and gonococcal genital infections according to gender. PID—pelvic inflammatory disease; STI—sexually transmitted infection.

Figure 2

Chlamydia trachomatis cell cycle of infection. This pathogen alternates between two distinct forms. The infectious form, named the elementary body (EB), when in contact with a host cell, can reach the cell cytoplasm by adhesion and internalization into a vacuole. Herein, EBs are converted into the alternative non-infectious form, the reticulate body (RB). These can go through the replication process, using the host’s resources, and using the cell’s energy and nutrients; when they reach a critical volume, the RBs transform into the previous form, the EBs. Finally, there are two possible mechanisms for the extracellular EB release, (1) lysis of the host cell or (2) extrusion. This cycle occurs repeatedly in the adjacent cells [12]. Figure created using BioRender.

Figure 3

Neisseria gonorrhoeae (NG) infection. Briefly, NG infection starts with the host cell interaction, establishing contact through some host cell receptors (CD46 and CR3) and type IV pili communication. After cell adhesion, this bacterium starts its replication and invasion processes, via transcytosis. Concomitantly, NG releases some cellular fragments, such as peptidoglycans and lipo-oligosaccharides (LOS), which, in contact with some cell surface molecules, namely, asialoglycoprotein receptor (ASGP-R) and carcinoembryonic antigen-related cell adhesion molecule family (CEACAM), can activate some signaling pathways (such as NF-kB pathway), triggering processes such as pro-inflammatory cytokine and chemokine production (including IL-1, IL-6, IL-8). In addition, this pro-inflammatory gradient of molecules drives the immune cell recruitment to the local, mainly dendritic, cells, macrophages, and neutrophils. Although these immune cells’ role is to trigger pathogen destruction, mostly through phagocytosis by neutrophils, up to the infection clearance, NG can frequently survive, and the infection can persist. Figure created using BioRender.