Chlamydiae are Gram-negative bacteria which comprises of 11 species that are pathogenic to humans and animals. The two major species responsible for infecting humans and inflicting a wide range of diseases are Chlamydia trachomatis and Chlamydia Pneumoniae. Chlamydia Trichomoniasis (Chlamydia) is the most commonly diagnosed bacterial sexually transmissible infection around the world and in Australia. This bacterium is transmitted through direct contact with infected tissues – including vaginal, anal or oral sex – and can also be passed from an infected mother to the newborn during childbirth. Despite being classified as a bacterium, Chlamydia’s unique infectious cycle and two developmental forms distinguish itself among other bacterial species. These unique features are epitomised by their infectious form called the elementary body (EB) and the reticulate body (RB). The elementary body is metabolically inactive and is taken up by the host cells, allowing the EB to differentiate into the metabolically active RB. Because Chlamydia is unable to produce its own energy source, RB heavily relies on consuming the host’s amino acids to replicate and form new EB, which enables itself to infect addition cells. C. trachomatis targets epithelial cells of the endocervix and upper genital tract in women, and the conjunctiva, urethra and rectum in both men and women. Chlamydial infections often produce few or no symptoms and many are left untreated. However, without proper treatment Chlamydia can potentially lead to severe health outcomes encompassing the reproductive systems – such pelvic inflammation disease, ectopic pregnancy and tubal factor infertility – as well as neonatal sequalae. Therefore, the severity of contracting Chlamydia coupled with its asymptomatic nature presents a significant global health challenge.
Globally, efforts to control the spread of Chlamydia and associated health effects have stemmed from promoting condom use, regular screening and providing access to diagnostic testing for those with symptoms or high-risk profiles. Despite these attempts to mitigate the prevalence of Chlamydia, notification rates have been steadily rising over the past decades, with the highest rates among the younger demographic who are aged between 15-29. In Australia, the highest notification rate is observed in Northern Territory, which records highest rates among Indigenous Australians. The rate in Aboriginal and Torres Strait Islander was 2.8 times that in the non-Indigenous population. There were 131 million incidents globally in 2012 among people aged 15- 49 years – 4.2% among women and 2.7% among men. Chlamydia is asymptomatic in up to 90% of infections and this is further exacerbated by the low screening rates in observed in Australian communities that precipitates into in re-infections. Additionally, Chlamydia is costing healthcare systems billions of dollars to treat not only the acute infections, but also the complications caused by its asymptomatic nature. The cost of treating the complications of undiagnosed Chlamydial infections, including PID and tubal infertility, are high both in psychosocial and in financial terms. Another major public health concern surrounding Chlamydia is its ability to facilitate the transmission of HIV infection in both male and females.
Previous studies indicated that Chlamydia can clear spontaneously in the absence of medication or any treatment due to the adaptive and innate immune response. However, since the 1996, the primary medication provided to individuals diagnosed with Chlamydia is antichlamydial antibiotics, particularly azithromycin (AZI). Prior research has established that AZI inhibits the growth of Chlamydia elemental bodies through impeding chlamydial life cycle at the RB-to-EB transition. AZI produces its antibacterial activity by inhibiting chlamydia’s protein synthesises with the stopping of the translocation/transpeptidation steps via binding to the 50S ribosomal subunit, resulting in the control of various bacterial infections. Azithromycin is prescribed to diagnosed patients by doctors and are commonly consumed orally once day for seven to fourteen days. Consequently, reports have highlighted that individuals undertaking Azithromycin as treatment for Chlamydia has a 96.6% cure rate. Clinical research findings surrounding AZI’s adverse outcomes exhibited consistent moderate gastrointestinal outcomes, including nausea, diarrhea, or flatulence. Although AZI exhibits effective and significant results in treating Chlamydia, doxycycline is another antibiotic that is also frequently prescribed to treat patients with Chlamydial infections. Similar to AZI, doxycycline inhibits bacterial growth of Chlamydia by binding onto the 30S subunit of the tRNA subunit of ribosomes, blocking tRNA activities. Therapy for Chlamydia using Doxycycline at 100mg is absorbed orally twice a day for seven days. Though Doxycycline is well tolerated, it is well known that an adverse of consuming this medication is the permanent discoloration and enamel hypoplasia of teeth. Other research has exhibited oesophageal erosion and photosensitivity were the main adverse events. Despite the adverse outcomes, Doxycycline is considered as one more effective therapeutic method to treat Chlamydia due to its near 100% success rate. For many years Azithromycin and Doxycycline have been the standard treatments for Chlamydia, however, recent reports have conveyed concerns regarding declines in cure rates for both these drugs due to antimicrobial resistance. Although other antibiotics including quinolones and amoxicillin have shown potential to in treating Chlamydia, there are concerns about their adherence due to the required multiday courses required during treatment. Alongside the antibiotic resistance, the asymptomatic nature of Chlamydial infection has attributed to the desire of discovering a new treatment, especially delivering an effective vaccine antigen to induce safe and effective immune effectors to confer long-term protective immunity. Despite all efforts in developing a vaccine has been unsuccessful, the current era of biodegradable polymeric nanoparticles and the adjuvanted derivatives may facilitate formulating a human vaccine in the foreseeable future. The potential of this vaccine in the future will enable lower rates of reinfection, while mitigating the asymptotic nature that exacerbates chlamydial infections, and promotes a reliable and cost-effective strategy. While studies surrounding vaccines for Chlamydia are continuously emerging, more details and research encapsulating immunostimulation by adjuvanted nanoparticles are required to empower developing this vaccine.
Chlamydia trachomatis is the most common sexually transmissible infection in the world and in Australia for the past decades. It is transmitted through a range of sexual activities, childbirth and direct contact with infected tissues. Most of individuals contracting this infection often exhibits no onset symptoms and can potentially lead to other diseases or other health problems is determinantal towards the quality of their lives. The current treatments via AZI and doxycycline have been effective in curing individuals with Chlamydia, however, it does not overcome the asymptomatic nature of this infection. Therefore, searching for other alternatives surrounding vaccines have been the pinnacle focus in overcoming the challenges.
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