Overview of Chlamydia – a Large Public Health Issue

Chlamydia is a common sexually transmitted disease caused by the gram-negative bacterium chlamydia trachomatis via sexual contact and is treated with antibiotics. Having numerous sexual partners and past history of chlamydial infection as well as inconsistent usage of condom increases the risk of being diagnosed with Chlamydia. Chlamydia infection begins when the elementary body comes in contact with the apical epithelial surface of a target cell. This triggers a series of early events which assist in Chlamydia programming and primes the host cell for productive infection. (Beatty, Morrison and Byrne, 1994) Studies show there is a higher rate of chlamydia infection in young women than men, especially between 15 to 24 years of age. In addition, risk is markedly increased in men and women with chlamydia trachomatis infection within the last 12 months and there is a major concern that about 65 – 70% of infected women and 50% of infected men are asymptomatic

Symptoms of Chlamydia

Symptoms of Chlamydia infection are dependent on infection site. Infection of the lower genital tract and urethra may cause abnormal vaginal discharge and dysuria whereas infection of the upper genital tract may cause abdominal or pelvic discomfort. If left untreated, Chlamydia may causes late complications including pelvic inflammatory disease, ectopic pregnancy, subfertility and infertility in women. In males, chlamydia infection causes acute epididymitis, nongonococcal urethritis and may also be associated with male infertility. (Peipert, 2003) Not only that, chlamydia also facilitates HIV transmission. (Ozolins, 2011) Despite having affordable and effective treatments, it is still a tough challenge to control Chlamydia as most people are asymptomatic and the infections can persist for several months. Therefore, it is difficult to determine the prevalence of Chlamydia because even if someone has the infection, he or she would not know until they get it checked. Not forgetting that it is also difficult to control the spread of Chlamydia infection as it can be passed on if your partner do not use contraception.

Life cycle of Chlamydia

Chlamydia alternates between two forms – the infectious, non-replicating and extracellular elementary body which displays zero activity, as well as the non-infectious, replicating and intracellular reticulate body. Infection beings when the small elementary body comes in contact with the epithelial cell surface. (AbdelRahman and Belland, 2005) After Chlamydia reaches the endoplasmic reticulum, the elementary body begins to transform into the larger metabolically active reticulate body. Thereafter, the elementary body’s DNA is relaxed, signals for DNA, RNA and protein synthesis are activated and reticulate body’s cell division ensues. (Belland et al., 2003) This intracellular Chlamydial miro-colony, together with nutrition depletion and ATP scavenging from the infected host, gives a signal for the transformation of the non-infectious reticulate body to be back into the infectious elementary body, which are then exocytosed from the host cell to infect neighbouring epithelial cells so as to perpetuate the process of infection.

The EB enters the host cell via endocytosis and upon gaining entry, it converts into the metabolically activate RB, which replicates within a vaculolar compartment known as the inclusion. Towards the end of the development cycle, the RBs differentiates back into EBs, stimulating lysis of the host cell and the release of infectious EBs into the extracellular space. These EBs then moves on to infect new host cells.

Before gaining entry into host cells, the antigen presenting cells engulf the EBS. Antibodies also bind to the EBs, neutralizing their ability to enter epithelial cells. Cytokines can also directly inhibit both the replication and development of Chlamydia trachomatis within cells. (Roan and Starnbach, 2007)

Host cells which has the replication of Chlamydia trachomatis going on will be lysed by CD8+ T cells.

Over the years, Chlamydia infection has been a large public health issue as it increases genital chlamydia infection such as pelvic inflammatory disease and a decrease in rates of reproduction, if it is being left untreated. On top of that, it also imposes a substantial cost burden on health care systems due to the complications they cause. Subfertility treatment is costly as in-vitro fertilization is expensive.

Besides that, Chlamydia is also difficult to cure due to the immune-evasion mechanisms that it possesses. With the presence of major outer-membrane and polymorphic membrane proteins, Chlamydia trachomatis has the ability to avoid being detected by antibodies, which lead to its enhanced survival outside of the host cells. Next, mitochondrial release of cytochrome C inhibition is another factor which contributes to Chlamydia trachomatis’s enhanced survival outside of host cells as it leads to inhibition of infected host cells. On top of all these, Chlamydia trachomatis also has the ability to thrive as alternative intracellular forms. The gene expression that encodes tryptophan synthase and a tryptophan repressor by genital strains of Chlamydia trachomatis supresses the growth inhibitory effect of Interferon- γ.

The production of interferon-γ by T cells brings about the expression of enzyme indolemaine-2,3-dioxygenase, which in turn lead to tryptophan degradation. (Beatty et al., 1994) Hence, insufficient tryptophan leads to Chlamydia trachomatis death through tryptophan starvation. Upon removal of Interferon-γ and replenishment of tryptophan, persistent forms of Chlamydia trachomatis starts to differentiate rapidly into infectious elementary bodies (EBs). Some strains of Chlamydia trachomatis carries a functional tryptophan synthase which has the ability to synthesize tryptophan, thereby allowing them to escape from the growth-inhibitory mechanism.

Chlamydia transmission can be reduced with the use of antibiotics. Without antibiotics, this bacteria can normally last for several months. Antibiotics azithromycin and doxycucline are widely used to treat Chlamydia infection, where the former is to be taken orally in a single dose, whereas the latter to be taken orally two times a day for a week. Azithromycin is said to be more effective than doxycucline as it’s a single dose therefore compliance is enhanced. However, Chlamydia trachomatis is starting to be resistant to antibiotics, with some clinical isolates having both single and multiple drug resistance when cultured in vitro.

Next, screening is also widely used to prevent prevalence of Chlamydia infection. It identifies seemingly healthy people who might be at risk of Chlamydia infection, whom will then be offered some information pertaining to the infection itself, further tests as well as appropriate treatment to reduce complications from arising. Screening aims to control and reduce chlamydia’s transmission and frequency respectively. At the same time, it lowers the risk of complication, especially reproductive tract complications in women. However, as certain affected people are symptomatic, screening of adolescents who are very often engaged in sexual activities is the only way to detect most chlamydia infections.

While screening programmes is widely used, it has not been very effective after all because repeated screening further lowers Chlamydia trachomatis’s baseline frequency, which in turn leads to inaccurate statistical evaluation. Other than that, screening for Chlamydia infection in asymptomatic patients with a long history of not being able to conceive children isn’t recommended as the sequelae are already apparent and a high percentage of subfertile males have been infected with Chlamydia trachomatis.

Future alternatives in alleviating Chlamydia trachomatis infection

Given that multi-subunit vaccines is more efficacious than vaccines based on single antigens, Chlamydia trachomatis vaccines candidates are likely to include various antigens in the future. It is important to focus on the identification of additional Chlamydia trachomatis antigens that induces protective T-cell responses and also on the mechanisms that promotes protective immunity in the female genital tract, and that is inclusive of the role of dendritic cells in antigen uptake and presentation as well as the role of pro-inflammatory cytokines in the influence of T-helper cells response biasness. Nucleic acid amplification tests (NATT) must also be considered in one of the tests of choice for diagnosting Chlamydia trachomatis infection as it provides diagnostic tests for Chlamydia trachomatis that are more sensitive than antigen or culture tests. Nucleotide sequences will be targeted by polymerase chain reaction and ligase chain reaction in the chlamydia cryptic plasmid. The plasmid measures approximately 10 copies per elementary body, hence being advantageous over a chromosomal DNA target in terms of sensitivity. Both PCR and LCR provide sensitivities over 90% and NAAT only have a few false-positive result-specificities reaching 100%.

All in all, despite having the current control mechanisms being utilized to fight Chlamydia infection, it is still not sufficient to greatly alleviate it. As our immune response to Chlamydia infection involves both innate and adaptive immunity, more research needs to be done in order to develop a vaccine as well as antibiotics which will be strong enough and also more effective in alleviating Chlamydia infection. Most importantly, it will be best for people who are affected with Chlamydia trachomatis to avoid engaging in any sexual activities for a week after taking the antibiotics.

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