What is Trachoma?

Trachoma is a bacterial infection of the eye transmitted by close person-to-person contact. With frequent and repeated infections, trachoma infection can lead to permanent visual impairment.

Global Burden

Trachoma

Trachoma has been eliminated from most of the developed world, but is still endemic in areas with poor sanitation, scarce water supply, and where people live in crowded conditions. It is especially prevalent in remote, rural areas of Africa, Asia, South America, and among aboriginal groups in Australia. Approximately 84 million people are currently infected with trachoma, of whom about 10% have some visual impairment.1 It is the most common infectious cause of blindness worldwide.2

Causative Agent

infected cellsTrachoma is caused by infection of the ocular surface with the bacterium Chlamydia trachomatis. The infection is spread by mucus membrane contact with an infected person (or their secretions) and by mechanical transmission by flies. As such, it often affects members of the same family who live together in close quarters, and disproportionately affects women and children.1

Pathogenesis

A single infection with C. trachomatis causes inflammation that resolves, whereas repeated infection can result in permanent damage to the cornea and even blindness. The World Health Organization (WHO) divides the development of trachoma into stages.

  1. Trachomatous inflammation - follicular
  2. Trachomatous inflammation - intense
  3. Trachomatous scarring
  4. Trachomatous trichiasis (eyelashes rubbing and damaging the cornea)
  5. Corneal Opacity2

The first two stages are ‘active stages,’ wherein the bacterial infection triggers a release of cytokines into the conjunctiva (the clear membrane that lines the eye and eyelid) causing swelling of the eyelid tissue. The later stages are the result of chronic inflammation and can lead to entropion (the formation of scar tissue that causes the eyelid to turn inward) with the lashes scratching and irreversibly damaging the corneal surface.3 Children more often display the active stages of infection, whereas older people – who have suffered repeated reinfection – exhibit marked scarring of the conjunctiva and visual impairment.

The absence of active bacterial infection in the later stages of the disease has implications for the management of trachoma; although antibiotics can kill the C. trachomatis bacteria, antibiotic treatment does not cure the irreversible eye damage caused by years of repeated infections.

Current Control Strategy

In 1998, the WHO formed the GET2020 alliance, a coalition of NGOs, industry and academic experts, and field doctors, with the goal of global trachoma elimination by 2020. The control strategy for trachoma prevention adopted by the group is the SAFE strategy1:

  • Surgery
  • Antibiotics to treat the reservoir of infection
  • Face washing
  • Environmental Change

Surgery to correct trichiasis (lashes turned inward and scratching the cornea) has proven to be successful in clinical trials, but there are issues of access and feasibility in the low-resource settings where trachoma is endemic. Temporary non-surgical methods of preventing eye damage – such as sticky tape to hold open the eyelid, or epilation to remove inward-growing eyelashes – are also often employed. Antibiotics are used in mass drug administration to reduce the disease prevalence, and in individual cases to end the infection. Face washing and environmental change go hand-in-hand, and are both potentially effective at reducing the probability of transmission of the bacteria. Unfortunately, these solutions also require the most significant expansion of infrastructure, which may not be possible in the types of places where trachoma is endemic.4

Existing Products

Drugs

While there are no drugs specifically targeted to C. trachomatis infection, azithromycin and tetracycline are the antibiotics of choice. Oral formulations of the drugs are often given in mass drug administrations, while topical ointments or eye drops are used to treat existing infections.5

Vaccines

There are currently no vaccines in use to prevent trachoma

Diagnostics

Diagnosis in the field is generally made based on clinical presentation in endemic areas, and treatment is therefore usually presumptive. A definitive diagnosis of active infection is made in the laboratory using enzyme immunoassays, serology, or identification of the C. trachomatisbacteria in microscopic evaluation of conjunctival tissue.6

A dipstick immunoassay rapid diagnostic test (RDT) developed by Cambridge researchers has been shown to be more effective for diagnosis of trachoma than the WHO grading system.7 Clinical diagnosis of late-stage visual impairment caused by trachoma using the WHO system allows health care workers to arrange for surgery or another physical interventions to prevent further corneal damage. However, diagnosis of active C. trachomatis infection allows health care workers to prescribe antibiotics, clearing the bacterial infection and potentially preventing eye damage at an earlier stage. Rolling out the C. trachomatis RDT in endemic areas therefore has the potential to improve the early detection of infections and improve the correct use of antibiotics to prevent permanent eye damage.7

References

  1. WHO trachoma fact sheet.
  2. Thylefors B et al (1987) “A Simple System for the Assessment of Trachoma and its Complications.” Bulletin of the World Health Organization 65(4).
  3. Burton M et al. (2009) “The Global Burden of Trachoma: A Review.” PLoS Neglected Tropical Diseases 3(10): e460. 
  4. Sumamo E et al. (2007) “The Cochrane Library and trachoma: an overview of reviews.” Evidence-Based Child Health: A Cochrane Review Journal 2(3): 943-964.
  5. Schachter J et al. (1999) “Azithromycin in control of trachoma.” The Lancet 354(9179): 630-635.
  6. Solomon AW et al (2004) “Diagnosis and Assessment of Trachoma.” Clinical Microbiology Reviews 17(4): 982-1011.
  7. Michel CEC et al (2006). “Field Evaluation of a rapid point-of-care assay for targeting antibiotic treatment for trachoma control: a comparative study.” The Lancet 367: 1585-1590. 

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Drugs

Although drug resistance to common antibiotics is a concern, numerous antibiotics are available to treat C. trachomatis infection. Vaccine development is the primary focus of new trachoma products

Vaccines

Analysis

Because the bacterium C. trachomatis also causes sexually-transmitted chlamydia infections, which are common in both the developed and developing worlds, there is potential to develop a vaccine that prevents both diseases. Although the two diseases are caused by different bacterial serotypes, there is potential to co-develop a vaccine using common protein antigens.

The immunogenic major outer membrane protein (MOMP) is common to all chlamydia strains and therefore represents a promising vaccine antigen. Studies using this protein have seen a reduction in bacterial shedding and an induction of both cellular and humoral immune response against C. muridarum, the mouse strain of chlamydia2. However, despite evoking an antibody response, recombinant vaccine candidates using this protein have not been successful at providing total protection against infection. Early research into a MOMP-based DNA vaccine has yielded mixed results, but a DNA prime and immune-stimulating boost combination is the most promising vaccine candidate thus far.3

Diagnostics

Analysis

Early detection of the disease is crucial to prevent the damaging long-term effects of repeated trachoma exposure. An RDT that enables targeted detection of new cases and rapid antibiotic treatment could vastly improve disease outcomes in endemic areas. A rapid diagnostic ‘dipstick’ test is currently in the process of being distributed and applied for this use.1 Early discovery around a new test in development includes use of stabilized biomaterials and flourophore with high sensitivity for detection.

References

  1. Michel CEC et al (2006). “Field Evaluation of a rapid point-of-care assay for targeting antibiotic treatment for trachoma control: a comparative study.” The Lancet 367(9522): 1585-1590.
  2. Carmichael JR et al (2011). “Induction of protection against vaginal shedding and infertility by a recombinant Chlamydia vaccine.” Vaccine 29(32): 5276-5283.
  3. Schautteet K et al (2011). “Chlamydia trachomatis vaccine research through the years.” Infectious Diseases in Obstetrics and Gynecology.

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The following series of tables describe the availability of tools for research, discovery, and development of novel drugs, vaccines, and diagnostics for trachoma. The tools listed in the following tables are not intended to be an all-inclusive list but rather capture the most common tools used for drug, vaccine, and diagnostic development. The tools for trachoma are not well developed. However, trachoma benefits from tools developed to study the related sexually transmitted form of the disease.

Drugs Development Tools

Basic Research: Target IdentificationTarget ValidationScreening: Hit/Lead Identification OptimizationPre-clinical ValidationClinical Validation

Genome: C. trachomatis GenBank library available

Key databases: GenBank

In vitro culture: Yes

Gene knock-outs: No 

Conditional gene knock-outs: No 

Transposon mutagenesis: No 

RNAi: No

Other antisense technology: No 

Viability assays: Yes  

Transcription microarrays: Yes

Proteomics: Yes

Crystal structures: Yes

Whole-cell screening assays: Yes

Enzymatic screening assays: Yes

Animal models: Yes

Monkeys and mice are most common

Monitoring treatment efficacy: Yes 

Availability of endpoints: Resolution of disease signs is considered a ‘clinical cure’ of C. trachomatisinfection, but there is no endpoint for Trachoma.

Availability of surrogate endpoints: No 

Access to clinical trial patients/sites: Yes

Vaccines Development Tools

Basic Research: Antigen IdentificationImmune Response CharacterizationClinical Validation

See drug development tools above

Predictive animal models: Murine models are most commonly used in sexually transmitted C. trachomatisstudies and in genetic studies. Primates are a more relevant human analogue for clinical symptoms in Trachoma studies. 

Detection of endogenous antigen specific response in clinical samples: Yes, antibodies to C. trachomatis Major Outer Membrane Protein (MOMP).

Natural immunity well characterized: No

Surrogate markers of protection: No 

Challenge studies possible: No

Diagnostics Development Tools

Basic Research: Biomarker IdentificationBiomarker ValidationClinical Validation

See drug development tools above

Biomarkers known: Yes 

Access to clinical samples: Yes 

Possible sample types: Eye fluids, blood

Access to clinical trial patients/sites: es 

Treatment available if diagnosed: Yes (treatment of infection, not of eye damage)

References

Get Involved

To learn how you can get involved in neglected disease drug, vaccine or diagnostic research and development, or to provide updates, changes, or corrections to the Global Health Primer website, please view our FAQs.