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Infectious Diseases Case Study 2018

Alicia Lim Sue Ling - 18224533

Chlamydia is a bacterial sexually transmitted infection (STI), caused by a microorganism

called Chlamydia trachoma. Chlamydia trachoma is an intracellular bacterium that has a cell

wall, reproduce asexually and is sensitive to antibiotics (Loucks, 1987).The pathogenic

bacterium has 18 serotypes; types A, B, Ba and C instigate eyes infections, types D to K

cause genital infections and neonatal infections. (Paavonen & Eggert-Kruse, 1999).

Chlamydia spp. are parasites that rely on host cells for energy, which differentiate them to

other bacteria (Malhotra et al, 2013).

Figure 1. The life cycle of Chlamydia trachomatis. ​During an infection, the infectious but
metabolically inactive elementary body (EB) is taken up by mucosal epithelial cells, surrounded by an
endosomal membrane to form an inclusion. Within inclusion, the inactive EB differentiates into a
metabolically active reticulate body (RB), which divides by binary fission. Within 40-48 hours, the RBs
undergoes secondary replication which transform back into infectious EBs ; subsequently released
from the inclusion by exocytosis to further infect neighbouring cells ( Brunham & Rey-Ladino).
Both animal and human forms of Chlamydia share a development cycle which alternates

between two morphological forms ; extracellular infectious elementary body (EB) and

intracellular non-infectious reticulate body (RB) (Bastidas, Elwell, Engel & Valdivia, 2013).

The differentiation of EB into metabolically active RB takes place in a membrane bounded

compartment known as the inclusion in the presence of an infection (AbdelRahman &

Belland, 2005). Nonetheless, the non-infectious RB form of C.trachomatis undergoes

replication by binary fission; consequently re-differentiate into EBs and are delivered out of

the host to further infect neighbouring cells (AbdelRahman & Belland, 2005).

Chlamydial infections present a significant problem in public health due to negative effects in

reproduction and high healthcare expenditures. Chlamydia trachomatis infection is a major

cause of mucopurulent cervicitis (MPC) which leads to several complications including pelvic

inflammatory diseases (PID), tubal infertility and poor reproductive outcomes. (Paavonen

and Eggert-Kruse, 1999). In addition, untreated chlamydia infections cause a risk of HIV

transmission (Malhotra et al, 2013). Multiple objective criteria such as oedema and induced

mucosal bleeding are conducted to diagnose MPC. However, there is a lack of evidence and

significant clinical symptoms of MPC as most cases of chlamydial cervicitis are

asymptomatic (Paavonen & Eggert-Kruse, 1999). PID refers to the infection of Fallopian

tubes, the uterus and adjacent pelvic structures. These infections are not associated with

pregnancy or invasive surgical procedures but rather with C.trachomatis (McCormack,1994).

When minimal symptoms do arise, patients with silent PID usually do not seek medical care

immediately. Due to this delay, there is an increased risk of long term Fallopian tube damage

(Hillis et al,1993). Studies reported that after each occurring PID episode, the risk for tubal

infertility and ectopic pregnancy tends to double, resulting in high tubal factor infertility

among all infertility (Westrom,1980, 1994). On the other hand, there are limited data and
studies concerning the impact of chlamydia trachomatis infection on male fertility; yet this

asymptomatic infection is one of the most prevalent sexually- transmitted bacterial infection

that cause inflammation of both urinary tract and accessory gland, followed by several

sequelae including infections in the canalicular system of the genital tract and loss of

function in specialised epithelial cells involved in spermatogenesis (Paavonen &

Eggert-Kruse, 1999). Besides, due to the asymptomatic nature of this infection, it become a

public concern as the risk of sexual transmission to female partners could to PID, ectopic

pregnancy and infertility (Paavonen & Eggert-Kruse, 1999). Apart from poor reproductive

outcomes, this infection is no doubt an expensive health problem due to the high costs

associated with not only treating the infection itself but also the complications of

undiagnosed chlamydia trachomatis infection (Beagley and Timms,2000). For instance, the

solutions for treating post PID and infertility include both tubal surgery and in vitro fertilization

are extremely costly resulting in high financial problems (Land, Van Bergen,Morre and

Postma ,2009). Consequently, the long terms impact of C.trachomatis infection become a

health and financial burden to the public.

Potential control mechanisms were discovered and developed to alleviate the spread of the

sexually transmitted C.trachomatis. Based on the development of cell cycle in C.trachomatis,

evidence showed that this strong immunogen stimulates both humoral and cell-mediated

immune response by associating pro-inflammatory chemokines and cytokines; including

IFN-γ, IL-2, and IL-12, in resolving a chlamydial infection (Malhotra et al, 2013 ; Paavonen &

Eggert-Kruse, 1999). The outcome of C.trachomatis infection heavily relies on the interaction

and balance of cytokines secreted by activated lymphocytes causing activation of

neutrophils, monocytes and T-lymphocytes (Paavonen & Eggert-Kruse, 1999). Activated

neutrophils migrate to the site of infection to destroy chlamydial EBs by reducing the initial

amplification of C.trachomatis; then inhibiting of spread within the female genital tract

(Malhotra et al, 2013). Secretion of interferon gamma (IFN-γ) by the accumulation of T

helper cells (Th1) has a direct physiological effect on Chlamydia, disrupting its growth

through a tryptophan-degrading enzyme; resulting in a reduction of tryptophan pool size and

insufficient nutrients for the bacteria (Matthews, George, Flegg, Stenzel & Timms, 2001). In

addition, the proinflammatory activity promotes other production of cytokines and

chemokines that are able to block intracellular replication of the C.trachomatis and enhances

cell death by apoptosis (Guerra et al, 1999).

Figure 2. Innate and adaptive immune responses to Chlamydial infection.​ When an

epithelial cell is infected, elementary bodies (EB) are released and triggered by the innate immune

system. Macrophages and dendritic cell migrate to the site of infection and initiates the release of

pro-inflammatory cytokines (IFN-γ and IL-10) (Malhotra et al, 2013 ; Paavonen & Eggert-Kruse, 1999).

These chemokines activates natural killer (NK) cells and stimulates the maturation of T cells into

either CD8+ or CD4+ T cells; leading to formation of T helper cells (Th1 and Th2). Accumulation of

Th1 also stimulates the secretion of more interferon gamma (IFN-γ). Th1 cell interact with B cells via

the T cell receptor (TCR) to produce antibodies against the chlamydial infection (Redgrove &

Mclaughlin, 2014).
However, the model of pathogenesis by which C. trachomatis progresses from acute to

chronic infection, and finally serious disease is yet to be fully determined (Debattista, 2003).

Therefore, alternative controls to prevent the spread of C.trachomatis including regular

screenings for early detection and treatment of undiagnosed lower genital tract infection as

most infected individuals are tend to be asymptomatic (Regan, Wilson & Hocking, 2008).

The development of vaccines for both men and women could be a future approach in

treating Chlamydia whilst reducing the public health burden (Regan, Wilson & Hocking,

2008). Hence, with more advanced and improved technologies in cell culturing and animal

models, allows further understanding of the pathogenic processes (Rank, 2012). This is a

future prospect that increases the hope for the development of vaccine against sexually

transmitted diseases.


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