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Research conducted in a number of African villages where trachoma is endemic has shown that a significant number of people without the disease are nonetheless infected with Chlamydia trachomatis – the causative agent of trachoma. The existence of such an infectious reservoir suggests that control strategies should incorporate the treatment of individuals living in close vicinity to clinical cases. In certain parts of the developing world, over 90% of the population can become infected with Chlamydia trachomatis, which, if left untreated, can cause chronic follicular conjunctivitis and ultimately, blinding corneal opacification. Without effective control programmes, the incidence of trachoma-related blindness could double by the year 2020. Chlamydia trachomatis is a relatively small bacterium, approximately 0.3 microns in diameter. It is incapable of growing outside of a living cell. The name of the organism derives from the Greek word "chlamys" for "cloak draped around the shoulder." The image of the cloak derives from the intracellular pathology of the organisms: the bacteria are "draped' around the infected cell's nucleus. Infection with Chlamydia trachomatis begins with attachment of the bacterium to cell surface receptors in the eye, throat, or genitalia and the infection thrives in areas of the body relatively inaccessible to immune protective agents such as phagocytes, T-cells, and B-cells. Treatment of infected individuals is generally achieved with a variety of antibiotics; azithromycin is the favoured drug due to its single-dose therapy, which, of course, can dramatically improve patient compliance. Azithromycin, given orally, is generally well tolerated and has proven highly effective in treating chlamydial infections. With the support of the International Trachoma Initiative and major donations of azithromycin through the Azithromycin Donation Programme, millions of persons infected with trachoma should already receive sight-saving therapy. Current treatment strategies for control of the disease use clinical signs to direct treatment to individuals and communities; however, the recent study by Matthew Burton and colleagues of the London School of Hygiene and Tropical Medicine, suggests that such an approach may fail to target a significant proportion of individuals infected with the trachoma pathogen. Dr. Burton's study set out to determine the extent to which clinically normal but infected individuals represent a source of Chlamydia trachomatis infection. Such information would provide valuable data to design more effective treatment strategies. Dr. Burton's research used the genetic technique of polymerase chain reaction (PCR) to quantify the infection load from conjunctival swab samples. Each of the samples was collected in a rural population in a trachoma endemic area of Gambia , in West Africa . PCR is a technique used to amplify specific sequences of DNA; researchers can also use PCR as a diagnostic tool to detect stretches of DNA specific to a given pathogenic organism. PCR has served as a major research tool in wide use since the mid-1980s; it earned its' inventor, Kary Mullis, the 1993 Nobel Prize in Chemistry. Quantitative real time PCR was used to estimate the number of copies of the Chlamydia trachomatis omp 1 gene in infected samples. The researchers then cross-referenced this information with clinical signs of trachoma. The researchers then estimated the infectious load of Chlamydia trachomatis using the PCR technique to amplify the chlamydial omp 1 gene from DNA retrieved from conjunctival swab samples. The load of infection was quantified as the number of copies of omp 1 per swab. The results ranged from less than 34 copies of omp 1 per swab to more than 390 copies of omp 1 per swab. Most infected individuals had relatively low copy numbers of the chlamydial omp 1 gene; however, researchers noticed a significant increase in infection load in patients with severe clinical signs of the disease. Of the 1,319 people examined, 7.2% were infected with Chlamydia trachomatis; however, only 24% of those infected individuals had clinically active signs of trachoma. In other words, most infected individuals did not have signs of active disease. Samples with high copy numbers of the omp 1 gene were consistent with more clinically severe disease. The data collected was also used to assess if access to a latrine or sharing sleeping quarters with a clinically active case of trachoma had any effect on the overall picture. A latrine in the family compound of the villages assessed appeared to have a protective effect while sharing a bedroom appeared to be an important risk factor for the transmission of trachoma. The most significant findings of the study demonstrated that if treatment was provided only to those individuals with active clinical signs of the disease then approximately only one quarter of infected individuals would have received antibiotics. However, an alternative model calculated that if antibiotics were provided to all those who shared a bedroom with individuals with active signs of clinical disease then approximately half of all infected cases would receive antibiotic treatment. From their findings, the authors of the study concluded that a treatment programme "that targets treatment only to individuals with signs of active trachoma would miss most of the cases of infection in this community." The researchers also noted that "a strategy that involves treating a whole unit of people containing one or more cases of clinically active disease would be more likely to succeed in delivering treatment to infected individuals. Mass antibiotic treatment of an entire village where the prevalence of active disease was 15% or more in children would deliver treatment to 90% of infected cases and would be a relatively efficient use of resources". Dr. Burton's group added that in "areas of low endemicity, such as the Gambia , antibiotic distribution strategies should include the treatment of clinically normal people who live alongside individuals with clinically active trachoma to maximise the delivery of treatment to those infected with Chlamydia trachomatis." Despite the promise of antibiotics like azithromycin in treating trachoma, the researchers cautioned that "uncertainty remains over the most effective way to use antibiotics to help eliminate trachoma as a blinding disease." Undoubtedly the data collected throughout the duration of the research conducted in the Gambia will provide a most useful platform from which maximal benefit may be achieved through strategic application of antibiotic treatments against Chlamydia trachomatis. More detail on the research findings of the Gambian study may be found in Investigative Ophthalmology & Visual Science, Vol. 44, No. 10, pp 4215-4222. Glossary: Infectious reservoir: a person, plant, animal or substance in which an infectious agent can normally live and reproduce and become transmitted to susceptible hosts. Polymerase chain reaction (PCR): method for amplifying DNA segments using alternate cycles of heating and cooling that generates multiple copies of the original target DNA. PCR is used as a research tool, a medical diagnostic tool and as a forensic tool in criminal cases. Quantitative real time PCR: a method of the polymerase chain reaction technique which allows one to calculate the concentration of original DNA in a target sample and representing a more quantitative read out. Infectious load: a quantitative measurement of the numbers of infectious agent present in a given clinical sample. Omp 1 gene: outer membrane protein gene 1 which codes for approximately 60% of the bacterium's outer membrane proteins. The gene exists as a single copy on the chlamydial chromosome. For more about what's new in trachoma research and what's being done around the world to fight the disease, see www.trachoma.org
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