**6. The future of chlamydia**

The past had unfolded to become the present and the present will continue to unfold into the future. Hence looking at the evolution of different aspects related to chlamydia from past to present, let us see what we might see at the forefront in future.

With rapid discoveries of new chlamydial species, there is definitely increasing risk of zoonoses in humans. *Chlamydia psittaci*—the causative microorganism of ornithosis, is the most well-known zoonotic pathogen. Chlamydiae are quite prevalent microorganisms in the animal kingdom. Constant human exposure via research keeps us always on the verge of contracting zoonoses.

Despite more than 20 years of screening programme and chlamydia testing in many countries and regions, chlamydia control strategies still rely on assumptions rather than robust evidence. The trend is shifting from the approach of diagnose and treat to more focused management of patients and their partners [57]. The focus is on management of disease rather than management of infection. A wide array of approaches are being proposed and tested for chlamydia control.

On one hand there's this notion developing regarding early antibiotic intervention programme and pre exposure prophylaxis in at risk population. A randomized study under "Ipergay trial" done in the MSM group used doxycycline prophylaxis that consisted of two doses of the drug administered after the sexual encounter within a period of 72 h. It reported that Doxycycline Post Exposure Prophylaxis decreases the incidence of a first symptomatic bacterial STI in at risk MSM [58]. Yet on other hand early antibiotic intervention strategy may have undesirable impact of reducing the herd immunity as it eliminates "bottlenecks to *Chlamydia* transmission" among humans [59].

Macrolides, quinolones and tetracyclines are the usual antimicrobials used to treat acute Chlamydial infections. However, Chlamydiae can develop "persistent forms (atypical reticular bodies)" that remain uninfluenced by usual available therapies [60]. This is not genetic resistance, but actually is phenotypic resistance. Persistent infections can turn to have clinically chronic courses.

So many questions and doubts revolve around antibiotics. One answer is leading us to the next new question. Hence there was a need to look at other options to battle with chlamydia. The focus is around a vaccine, alternative therapies for chlamydia and educating humans for being responsible for their sexual behavior. A vaccine for chlamydia carries the hope of an ideal protective strategy. Why is there an evolving urgent need of vaccine against chlamydial infection? An infection that has accessible antibiotic treatment but behaves exactly like its name—a cloaked organism. A magical cloak that allows it to spread rapidly, create new variants, have high rates of re-infection, be asymptomatic so often yet lead to drastic sequelae that has potential to change the nature's human anatomy and physiology by rendering it infertile or play a probable role in carcinogenesis! Accessible treatment, screening programmes and awareness programmes leading with—"Chlamydia is not a flower" have not been enough! The quest for an effective vaccine has utilized multiple chlamydial species and their different antigens. The trajectory of different antigens has included whole cell and subunit vaccines—utilizing Major Outer Membrane Proteins, Polymorphic Membrane Proteins, Plasmid antigens etc. MOMP has shown promising results. The challenge in the vaccine development has been it's mucosal protective immunity and robust immune response. After more than 70 years of several vaccine trials, first in human vaccine trial via both intramuscular and intranasal routes, has reported good immunogenicity with good tolerability. "Antigen CTH522 with either CAF01 liposomes or aluminium hydroxide (AH)" as adjuvants were studied, where liposomal adjuvant formulation had a better profile [61]. A variety of alternative therapies are also being utilized to derive whatever benefit they might provide. Non antibiotic approaches include synthetic drugs like "Broad-Spectrum Antiviral Compound ST-669", a "small-molecule inhibitor of type III secretion INP0400", "Lipopolysaccharide-Binding Alkylpolyamine DS-96"; polyphenols like "Baicalin, luteolin and catechins". Peptides like "Transferrin", "WLBU2 Peptide", "Cecrotin peptides", "Cathelicidin peptides", "Spider venom peptides" etc. have also shown slow therapeutic effect. The hurdle with these alternative therapies is that they are needed in high concentrations where they have unpredictable efficacy [62]. Vitamin E supplementation has shown increased humoral response towards chlamydia [63]. Interferon and interferon inducers have shown reduced growth of chlamydiae in vitro, when subjected to it six or eighteen hours prior to infection, and when treated early (within four hours) after infection reduced yield was detected in the cell cultures [64].

Recently the interest has spiked in anti-infective drugs that disarm the organism and help the host immunity in clearing infection. This surpasses the hurdle of antimicrobial resistance. For example—small-molecule LpxC inhibitors blocks the synthesis of lipopolysaccharide in Chlamydia due to which it replicates within vacuoles

*Chlamydia: The Secret Enemy from the Past to Present, and Future DOI: http://dx.doi.org/10.5772/intechopen.110902*

intracellularly, but cannot transition into the invasive form—"the elementary body". Yet there is time for further development of such drugs and whether they can be commercially viable therapeutics [59].

Single measures or a few combined measures are not what will help control Chlamydia. Impeccable efforts to develop a plan with designed steps, is the need for any major success. An "Integrated Care Model with Implementation Roadmap to Improve *C. trachomatis* Management and Control" has been developed in India [65]. It focuses on 4 key areas- Awareness, timely and effective management, aggressive follow up, and prevention. In developing countries the barriers to Chlamydia control narrow down to two main categories—Logistics & Resources and Culture & Education.

It is seen that younger age has higher association with *C. trachomatis* infection prevalence, due to more risky sexual behavior. Hence the role of timely sex education in pre-adolescence or adolescence with sufficient information about such STIs and the protection measures could lead to a more responsible and informed young adult population. This could culminate into a healthier thriving young population over the years [66]**.**
