Search tips
Search criteria

Results 1-25 (884833)

Clipboard (0)

Related Articles

1.  An Innovative Smartphone-Based Otorhinoendoscope and Its Application in Mobile Health and Teleotolaryngology 
The traditional otorhinoendoscope is widely used in the diagnosis of a variety of ear and nose diseases, but only one doctor can use it at a time. It is also very difficult to share observations from one doctor with another doctor. With advances in electronic health technology, the extended potential application of smartphones to support medical practice or mobile health has grown steadily.
The first phase of the study discussed how smartphones may be used for otorhinoscopic imaging and image management via an innovative adaptor. The second phase of the study was to evaluate the diagnostic capability of the smartphone-based otorhinoendoscope, as compared to the traditional otorhinoendoscope, and its application in mobile health and teleotolaryngology.
We designed a unique adaptor to connect the otorhinoendoscope and smartphone in order to perform smartphone-based otorhinoendoscopy. The main aim was to transform the smartphone into an otorhinoendoscope. We devised a method that would allow us to use the smartphone’s camera to capture otorhinoscopic images. Using a freely available Web-based real-time communication application platform and the 3G (or WIFI) network, the smartphone-based otorhinoendoscope could synchronize the smartphone-based otorhinoscopic image with smartphones, tablet PCs, computer notebooks, or personal computers.
We investigated the feasibility of telemedicine using a smartphone, tablet PC, and computer notebook. Six types of clinical otorhinoscopic images were acquired via the smartphone-based otorhinoendoscope from six patients, which were examined in this study. Three teleconsultants (doctors A, B, and C) reviewed the six types of clinical otorhinoscopic images and made a telediagnosis. When compared to the face-to-face diagnosis, which was made in-person via a traditional otorhinoendoscope, the three teleconsultants obtained scores of a correct primary telediagnosis 83% (5/6), 100% (6/6), and 100% (6/6) of the time, respectively. When the clinical data were provided, the three teleconsultants obtained a correct secondary telediagnosis score of 100% (6/6), 100% (6/6), and 100% (6/6) of the time, respectively.
The use of previously available technologies in the absence of any additional expensive devices could significantly increase the quality of diagnostics while lowering extraneous costs. Furthermore, this could also increase the connectivity between most isolated family doctors and remote referral centers.
PMCID: PMC3961810  PMID: 24590187
otorhinoendoscope; smartphone; mobile health; teleotolaryngology; telediagnosis
2.  Correlation of Clinical Trachoma and Infection in Aboriginal Communities 
Trachoma is the leading infectious cause of blindness due to conjunctival infection with Chlamydia trachomatis. The presence of active trachoma and evidence of infection are poorly correlated and a strong immunologically-mediated inflammatory response means that clinical signs last much longer than infection. This population-based study in five Aboriginal communities endemic for trachoma in northern Australia compared a fine grading of clinical trachoma with diagnostic positivity and organism load.
A consensus fine grading of trachoma, based on clinical assessment and photograding, was compared to PCR, a lipopolysacharide (LPS)-based point-of-care (POC) and a 16S RNA-based nucleic acid amplification test (NAAT). Organism load was measured in PCR positive samples.
A total of 1282 residents, or 85.2% of the study population, was examined. Taking the findings of both eyes, the prevalence of trachomatous inflammation-follicular (TF) in children aged 1–9 years was 25.1% (96/383) of whom 13 (13.7%) were PCR positive on the left eye. When clinical data were limited to the left eye as this was tested for PCR, the prevalence of TF decreased to 21.4% (82/383). The 301 TF negative children, 13 (4.3%) were PCR positive. The fine grading of active trachoma strongly correlated with organism load and disease severity (rs = 0.498, P = 0.0004). Overall, 53% of clinical activity (TF1 or TF2) and 59% of PCR positivity was found in those with disease scores less than the WHO simplified grade of TF.
Detailed studies of the pathogenesis, distribution and natural history of trachoma should use finer grading schemes for the more precise identification of clinical status. In low prevalence areas, the LPS-based POC test lacks the sensitivity to detect active ocular infection and nucleic acid amplification tests such as PCR or the 16S-RNA based NAAT performed better. Trachoma in the Aboriginal communities requires specific control measures.
Author Summary
Repeated episodes of C. trachomatis infection lead to active trachoma clinically characterised by an often intense inflammatory response to chlamydial antigens with later scarring and distortion of the eyelid leading to blindness. However, the clinical signs of trachoma do not correlate well with laboratory tests to detect the presence of Chlamydia. The WHO simplified clinical grading scheme currently used for assessment of trachoma has a poor correlation with C. trachomatis genomic test findings, even though the detection of bacterial genome is strongly correlated with the prevalence and severity of active trachoma. A detailed assessment of the clinical signs using a finer grading system was studied in a population-based survey in five Australian Aboriginal communities. Much clinical activity and infection was found in those with clinical signs below the threshold used in the current WHO grading scheme. Future studies of the distribution of infection and pathogenesis should use finer grading methods than the current WHO scheme. The prevalence of trachoma in these communities confirms that trachoma remains of public health importance and sustained interventions to control trachoma are warranted.
PMCID: PMC3057949  PMID: 21423648
3.  Conjunctival FOXP3 Expression in Trachoma: Do Regulatory T Cells Have a Role in Human Ocular Chlamydia trachomatis Infection? 
PLoS Medicine  2006;3(8):e266.
Trachoma, caused by ocular infection with Chlamydia trachomatis, remains the leading infectious cause of blindness and in 2002 was responsible for 3.6% of total global blindness. Although transmission can be successfully interrupted using antibiotics and improvements in public and personal hygiene, the long-term success of the control programmes advocated by the World Health Organization are still uncertain. For the complete control and prevention of trachoma, a vaccine would be highly desirable. Currently there are no licensed vaccines for trachoma, and no human vaccine trials have been conducted since the 1960s. A barrier to new attempts to design and introduce a vaccine is the identification of immunologic correlates of protective immunity or immunopathology. We studied important correlates of the immune response in a trachoma-endemic population in order to improve our knowledge of this disease. This is essential for the successful development of a vaccine against both ocular and genital C. trachomatis infection.
Methods and Findings
We used quantitative real-time PCR for C. trachomatis 16S rRNA to identify conjunctival infection. The expression of IFN-γ, IDO, IL-10, and FOXP3 mRNA transcripts was measured. We evaluated the role of immune effector and regulatory responses in the control of chlamydial infection and in the resolution of clinical signs of trachoma in endemic communities in Gambia. All host transcripts examined were detectable even in normal conjunctiva. The levels of these transcripts were increased, compared to normal uninfected conjunctiva, when infection was detected, with or without clinical disease signs. Interestingly, when clinical disease signs were present in the absence of infection, the expression of a regulatory T cell transcription factor, FOXP3, remained elevated.
There is evidence of an increase in the magnitude of the local anti-chlamydial cytokine immune responses with age. This increase is coupled to a decline in the prevalence of infection and active trachoma, suggesting that effective adaptive immunity is acquired over a number of years. The anti-chlamydial and inflammatory immune response at the conjunctival surface, which may control chlamydial replication, is closely matched by counter inflammatory or regulatory IL-10 expression. Differences in the level of FOXP3 expression in the conjunctiva may indicate a role for regulatory T cells in the resolution of the conjunctival immune response, which is important in protection from immunopathology. However, the expression of cytokines that control chlamydial replication and those that regulate the conjunctival immune response is not simply juxtaposed; the interaction between the infection and the clinical disease process is therefore more complex.
The immune response in a trachoma-endemic population showed an increase in local anti-chlamydial cytokine responses with age, associated with a decline in the prevalence of infection and active trachoma.
Editors' Summary
Trachoma is the leading infectious cause of blindness worldwide. Six million people—most of whom live in crowded, unhygienic conditions with limited water supplies—are blind because of repeated eye infections with Chlamydia trachomatis. This bacterium passes easily from person to person on hands or clothing and is also spread by flies. Successive infections starting in childhood cause progressive scarring of the inside of the eyelid. Eventually, the eyelashes turn inwards and rub painfully over the front of the eye (the cornea). This causes corneal scarring, loss of corneal transparency, and, finally, irreversible loss of sight, usually in adulthood. C. trachomatis infections can be prevented by improving personal hygiene and by reducing fly breeding sites, and they can be treated with antibiotics. In addition, early scarring of the eyelid and turned-in eyelashes can be treated surgically.
Why Was This Study Done?
Through the above interventions, the World Health Organization hopes to eliminate trachoma by 2020, but a vaccine might also be necessary. To develop a vaccine, the human immune response to C. trachomatis needs to be better understood. As with other diseases, the immune response to C. trachomatis includes a pro-inflammatory side, which activates immune cells to attack the bacteria, and a regulatory side, which keeps the pro-inflammatory responses in check. The balance between these two sides is not perfect, however. Although the immune response deals with C. trachomatis infections efficiently, it also causes some of the tissue damage that leads to scarring and loss of sight. In this study, the researchers have investigated the human immune response to C. trachomatis to provide immunological information that might help vaccine development.
What Did the Researchers Do and Find?
The researchers examined school children living in Gambia, where trachoma is very common, for clinical signs of active trachoma (for example, red or swollen eyelids). To find out which children were infected with C. trachomatis, the researchers collected a few cells from the surface of their eyes and looked for a ribonucleic acid (RNA) molecule that is only made by C. trachomatis. The researchers also looked in these samples for human messenger RNA (mRNA) molecules that are made during pro-inflammatory and regulatory immune responses.
The children formed four groups based on infection with C. trachomatis and clinical signs. Some children—particularly the older ones—were uninfected and had no clinical signs. Others were infected but showed no clinical signs—these children were incubating the bacteria. Some were infected and had clinical disease; these children had the highest bacterial loads. Finally, children recovering from an infection carried no bacteria but still had some clinical signs.
The researchers detected different types of immune response in each of these groups. Children incubating the bacteria had a strong pro-inflammatory response—their immune systems were trying to fight off infection. The pro-inflammatory response was even stronger in the infected children with clinical signs, but now the regulatory response had also increased, presumably to limit inflammation. In children in the recovery phase, only regulatory immune cells, which were making an mRNA from a gene called FOXP3, remained active.
What Do These Findings Mean?
The relative rarity of infections and active disease in older children together with indications of a more active immune response to infection indicates that protective immunity to C. trachomatis is acquired through repeated exposure to it. This bodes well for the development of a vaccine, which would speed up the acquisition of this natural immunity. Furthermore, the new information about immune responses at different stages of infection with C. trachomatis should help in vaccine design. The findings need to be confirmed by tracking immune responses in individual children during episodes of infection, but could then be used to help design vaccines that produce good protective immunity against C. trachomatis without causing too much collateral tissue damage. The current results suggest, for example, that regulatory immune cells are important in limiting the inflammatory response, so vaccine developers may need to ensure that their vaccines stimulate the production of this sort of cell as well as of the pro-inflammatory cells needed to clear the infection.
Additional Information.
Please access these Web sites via the online version of this summary at
• NHS Direct Online patient information on trachoma
• World Health Organization information on trachoma and its elimination
• US Centers for Disease Control and Prevention general information on trachoma
• MedlinePlus encyclopedia entry on trachoma
PMCID: PMC1526769  PMID: 16881731
4.  The detection of Chlamydia trachomatis by direct immunofluorescence in conjunctival smears from patients with trachoma and patients with ophthalmia neonatorum using a conjugated monoclonal antibody. 
The Journal of Hygiene  1986;96(1):83-87.
Duplicate specimens were taken with cotton-wool swabs from the upper tarsal conjunctiva of 63 patients living in Gambian villages in which trachoma is endemic and from 34 infants with ophthalmia neonatorum (ON) attending an outpatient clinic in The Gambia. The detection of Chlamydia trachomatis by direct immunofluorescence (IF) using a conjugated monoclonal antibody to its principal outer membrane protein was compared with isolation in cycloheximide-treated McCoy cells. For trachoma, the sensitivity and specificity of the immunofluorescent technique were 62% and 100% respectively if ten elementary bodies (EBs) was taken as the minimum requirement for positivity by IF. If all cases with one or more EB were considered positive, the sensitivity was 81% and the specificity 85%. For ON the sensitivity and specificity were 100% and 95% respectively, regardless of which criterion was used. In view of its simplicity and easy applicability to field conditions it seems likely that direct IF using monoclonal antibodies may be a useful technique for the detection of C. trachomatis in the conjunctival epithelium of patients with trachoma.
PMCID: PMC2129581  PMID: 3512704
5.  Multiple Chlamydiaceae Species in Trachoma: Implications for Disease Pathogenesis and Control 
PLoS Medicine  2008;5(1):e14.
Chlamydia trachomatis is a unique obligate intracellular bacterium that remains the leading cause of sexually transmitted bacterial diseases and preventable blindness worldwide. Chronic ocular infections are referred to as trachoma, and predominate in developing countries. Since 2001, the World Health Organization has promoted control strategies including antibiotics, improved hygiene, and environmental measures with limited success. Consequently, a vaccine is urgently needed. Integral to vaccine design is an understanding of the interactions of the pathogen and host immune response. Various animal models of trachoma show that urogenital C. trachomatis strains and other species of the family Chlamydiaceae produce severe conjunctival inflammation and scarring similar to that of the ocular C. trachomatis strains. However, we do not know the extent of organisms that may be involved in human trachoma. Furthermore, C. trachomatis heat shock protein 60 (Hsp60) has been implicated in inflammation and conjunctival scarring but the role of other Chlamydiaceae Hsp60 in disease pathogenesis has not been examined. In this study, we set out to identify whether other Chlamydiaceae species are present in trachoma, and determine their association with severity of clinical disease and with mucosal and systemic immune responses to Chlamydiaceae species-specific Hsp60 to further investigate the immunopathogenesis of this blinding disease.
Methods and Findings
We randomly selected nine of 49 households in a trachoma-endemic region of Nepal. Trachoma was graded, and real-time, quantitative (k)PCR was used to detect genomic DNA and cDNA (from RNA) for Chlamydiaceae ompA and 16S rRNA genes, respectively, from conjunctival swabs. IgG antibody responses to recombinant (r) Chlamydiaceae species-specific Hsp60 were determined for tears and sera. Surprisingly, all three species—C. trachomatis, Chlamydophila psittaci, and Chlamydophila pneumoniae—were detected in eight (89%) study households; one household had no members infected with C. pneumoniae. Of 80 (63%; n = 127) infected individuals, 28 (35%) had infection with C. psittaci, or C. pneumoniae, or both; single and dual infections with C. psittaci and C. pneumoniae were significantly associated with severe conjunctival inflammation (OR 4.25 [95% confidence interval (CI), 2.9–11.3], p = 0.009] as were single infections with C. trachomatis (OR 5.7 [95% CI, 3.8–10.1], p = 0.002). Of the 80 infected individuals, 75 (93.8%) were also positive for 16S rRNA by kPCR for the same organism identified by ompA. Individuals with tear IgG immunoreactivity to Chlamydiaceae rHsp60 were eight times more likely than individuals without tear immunoreactivity to be infected (95% CI 6.4–15.1; p = 0.003), 6.2 times more likely to have severe inflammation (95% CI 4.4–12.6; p = 0.001), and 5.7 times more likely to have scarring (95% CI 3.9–11.1; p = 0.019) while individuals with serum IgG immunoreactivity were 4.1 times more likely to be infected (95% CI 3.1–10.1; p = 0.014).
We provide substantial evidence for the involvement of C. psittaci and C. pneumoniae, in addition to C. trachomatis, in trachoma. The distribution of Chlamydiaceae species by household and age suggests that these infections are widespread and not just sporadic occurrences. Infection with multiple species may explain the failure to detect chlamydiae among active trachoma cases, when only C. trachomatis is assayed for, and the failure of clinically active cases to resolve their disease following what would be considered effective C. trachomatis treatment. The evidence for viable (RNA-positive) organisms of all three species in single and coinfections, the significant association of these infections with severe inflammation, and the significant association of tear and serum IgG responses to Chlamydiaceae Hsp60 with inflammation and scarring, support the role of all three species in disease pathogenesis. Thus, while our findings should be confirmed in other trachoma-endemic countries, our data suggest that a reevaluation of treatment regimens and vaccine design may be required. Understanding the full impact of Chlamydiaceae species on the epidemiology, immunopathology, and disease outcome of trachoma presents a new challenge for Chlamydiaceae research.
In a study of trachoma cases within households in Nepal, Deborah Dean and colleagues find involvement of the Chlamydia species C. psittaci and C. pneumoniae in addition to C. trachomatis.
Editors' Summary
Six million people—most of whom live in crowded, unhygienic conditions in developing countries—are blind because of an infectious disease called trachoma. It is generally accepted that trachoma is caused by Chlamydia trachomatis, bacteria that pass easily between people on hands and clothing. Infection usually occurs first during childhood, but people do not become blind until adulthood. Successive infections cause progressive scarring of the inside of the eyelid. Eventually, the eyelashes turn inward and rub painfully over the front of the eye (the cornea). This causes corneal scarring, loss of corneal transparency and, finally, irreversible blindness. C. trachomatis infections can be prevented by improving personal hygiene (in particular, facial cleanliness in children) and by reducing fly breeding sites, and they can be treated with antibiotics. However, C. trachomatis and other organisms appear to be developing drug resistance to antibiotics commonly used to treat these infections. In addition, early scarring and in-turned eyelashes can be treated surgically, although recurrence of the in-turned eyelashes frequently occurs months to years after surgery.
Why Was This Study Done?
The World Health Organization has been promoting these “SAFE” interventions (surgery, antibiotics, facial cleanliness, and environmental improvement) since 2001 with the aim of eliminating trachoma by 2020. However, these control measures have had limited success so far and it looks like a vaccine may also be needed. To develop an effective vaccine, scientists need to know whether all cases of human trachoma are caused by so-called ocular strains of C. trachomatis. Might C. trachomatis strains that are usually associated with sexually transmitted disease (urogenital strains) or different species in the family Chlamydiaceae also cause human trachoma as work in animals has suggested? In this study, the researchers have investigated which Chlamydiaceae species are associated with trachoma in a region of Nepal where the disease is endemic (always present).
What Did the Researchers Do and Find?
The researchers examined all the members for trachoma in nine randomly selected households in a Nepali village. They then used sensitive molecular biology methods to identify the species in the family Chlamydiaceae and strains present in the eyes of the infected individuals. One third of them were infected with only C. trachomatis (mainly ocular strains but also some urogenital strains), one in five were infected with only Chlamydophila psittaci, and one in ten with only Chlamydophila pneumoniae. The other infected individuals had mixed infections. Infection with C. psittaci and/or C. pneumoniae was strongly associated with severe eye inflammation as was infection with C. trachomatis alone. The researchers also asked whether there were any antibodies (proteins made by the immune system that recognize infectious organisms) in the tears or blood of the infected individuals that recognized the Hsp60 protein of each Chlamydiaceae species; an immune response to C. trachomatis Hsp60 is thought to be involved in the inflammation and scarring seen in trachoma. Individuals with antibodies in their tears to Chlamydiaceae Hsp60, the researchers report, were eight times as likely to be actively infected with these bacteria and six times as likely to have severe eye inflammation as individuals without the antibodies.
What Do These Findings Mean?
These findings provide evidence for the widespread involvement of C. psittaci, C. pneumoniae, and urogenital strains of C. trachomatis as well as ocular strains of C. trachomatis in trachoma and might explain why some people with active trachoma do not have C. trachomatis in their eye secretions and why antibiotics that kill C. trachomatis effectively do not cure all cases of trachoma. However, because live bacteria were not isolated from patients and shown to cause disease in a model system, these findings do not prove that Chlamydiaceae other than C. trachomatis cause trachoma. Some or all of the bacterial strains and species detected in this study may be innocent bystanders although the strong association between their presence and severe inflammation and the association between antibody responses to Chlamydiaceae Hsp60 and inflammation argues against this possibility. If the involvement of multiple Chlamydiaceae strains and species is confirmed and extended in other trachoma-endemic regions, then future antimicrobial therapies and vaccines will need to deal with all these bacteria and not just C. trachomatis.
Additional Information.
Please access these Web sites via the online version of this summary at
The MedlinePlus encyclopedia contains a page on trachoma (in English and Spanish)
The World Health Organization provides information on trachoma (mainly in English but some information is available in French, Russian, and Spanish)
The US Centers for Disease Control and Prevention provides a technical fact sheet on trachoma
The charity Sightsavers International also provides information on trachoma and global efforts to eliminate the disease
The Carter Center provides an overview of trachoma control and a description of its trachoma control program
PMCID: PMC2174965  PMID: 18177205
6.  Molecular epidemiology of trachoma in a Gambian village. 
The application of a diagnostic and genotyping technique based on the polymerase chain reaction (PCR) to the study of trachoma epidemiology in the Gambian village of Jali is reported. PCR based on the major outer membrane protein (MOMP) gene of Chlamydia trachomatis appears to be more sensitive than either isolation or antigen detection by enzyme immunoassay; it had a specificity of 95% and sensitivity of 51% against clinical signs. PCR genotyping identified genotypes A and B of Chlamydia trachomatis circulating in Jali. Sequencing revealed a Pst1 restriction endonuclease site in the amplified MOMP gene of some B strains but not others; Pst1 digestion of the PCR product proved an easy method of distinguishing these strains. The distribution of serotypes and B strain variants shows a significant degree of household clustering (p < 0.001). PCR based genotyping combined with strain typing provides a new and powerful epidemiological tool for the study of transmission events in trachoma.
PMCID: PMC504962  PMID: 7848974
7.  Active Trachoma and Ocular Chlamydia trachomatis Infection in Two Gambian Regions: On Course for Elimination by 2020? 
Trachoma has been endemic in The Gambia for decades. National trachoma control activities have been in place since the mid-1980's, but with no mass antibiotic treatment campaign. We aimed to assess the prevalence of active trachoma and of actual ocular Chlamydia trachomatis infection as measured by polymerase chain reaction (PCR) in the two Gambian regions that had had the highest prevalence of trachoma in the last national survey in 1996 prior to planned national mass antibiotic treatment distribution in 2006.
Methodology/Principal Findings
Two stage random sampling survey in 61 randomly selected Enumeration Areas (EAs) in North Bank Region (NBR) and Lower River Region (LRR). Fifty randomly selected children aged under 10 years were examined per EA for clinical signs of trachoma. In LRR, swabs were taken to test for ocular C. trachomatis infection. Unadjusted prevalences of active trachoma were calculated, as would be done in a trachoma control programme. The prevalence of trachomatous inflammation, follicular (TF) in the 2777 children aged 1–9 years was 12.3% (95% CI 8.8%–17.0%) in LRR and 10.0% (95% CI 7.7%–13.0%) in NBR, with significant variation within divisions (p<0.01), and a design effect of 3.474. Infection with C. trachomatis was found in only 0.3% (3/940) of children in LRR.
This study shows a large discrepancy between the prevalence of trachoma clinical signs and ocular C. trachomatis infection in two Gambian regions. Assessment of trachoma based on clinical signs alone may lead to unnecessary treatment, since the prevalence of active trachoma remains high but C. trachomatis infection has all but disappeared. Assuming that repeated infection is required for progression to blinding sequelae, blinding trachoma is on course for elimination by 2020 in The Gambia.
Author Summary
Trachoma is the leading infectious cause of blindness worldwide, and is mainly found in tropical and poor countries. It is caused by infection of the eyes with the bacterium Chlamydia trachomatis. However, sometimes the clinical signs of disease can be present without infection being detected. Control efforts involve surgery, antibiotic treatment, face washing, and environmental improvement for better hygiene. Surveys of trachoma help countries to know whether and where they should implement control interventions. The Gambia is found in West Africa and has suffered from trachoma for decades. We conducted a survey of two Gambian regions to look at how much trachoma disease and C. trachomatis infection there is in the eyes. We found that although there was enough disease (≥10%) to warrant antibiotic treatment for everyone in the regions, there was nearly no infection (0.3%). This means that using clinical signs alone to make treatment decisions in low prevalence settings like The Gambia can lead to the waste of scarce resources. Our results also suggest that since less than 1% of children are infected with C. trachomatis, The Gambia is on course to achieve the World Health Organization's aim of eliminating blinding trachoma by the year 2020.
PMCID: PMC2791206  PMID: 20027217
8.  Profound and Sustained Reduction in Chlamydia trachomatis in The Gambia: A Five-Year Longitudinal Study of Trachoma Endemic Communities 
The elimination of blinding trachoma focuses on controlling Chlamydia trachomatis infection through mass antibiotic treatment and measures to limit transmission. As the prevalence of disease declines, uncertainty increases over the most effective strategy for treatment. There are little long-term data on the effect of treatment on infection, especially in low prevalence settings, on which to base guidelines.
Methodology/Principal Findings
The population of a cluster of 14 Gambian villages with endemic trachoma was examined on seven occasions over five years (baseline, 2, 6, 12, 17, 30 and 60 months). Mass antibiotic treatment was given at baseline only. All families had accessible clean water all year round. New latrines were installed in each household after 17 months. Conjunctival swab samples were collected and tested for C. trachomatis by PCR. Before treatment the village-level prevalence of follicular trachoma in 1 to 9 year olds (TF%1–9) was 15.4% and C. trachomatis was 9.7%. Antibiotic treatment coverage was 83% of the population. In 12 villages all baseline infection cleared and few sporadic cases were detected during the following five years. In the other two villages treatment was followed by increased infection at two months, which was associated with extensive contact with other untreated communities. The prevalence of infection subsequently dropped to 0% in these 2 villages and 0.6% for the whole population by the end of the study in the absence of any further antibiotic treatment. However, several villages had a TF%1–9 of >10%, the threshold for initiating or continuing mass antibiotic treatment, in the absence of any detectable C. trachomatis.
A single round of mass antibiotic treatment may be sufficient in low prevalence settings to control C. trachomatis infection when combined with environmental conditions, which suppress transmission, such as a good water supply and sanitation.
Author Summary
Trachoma is the most common infectious cause of blindness worldwide. Mass antibiotic treatment with azithromycin is used to control ocular Chlamydia trachomatis infection. There is uncertainty over how frequently and for how long treatment is needed, particularly in low prevalence settings. This study examines the effect of a single round of treatment on clinical disease and infection in a cluster of trachoma endemic Gambian villages over a five-year period. These villages had good water supplies and sanitation improved part way through the study. We found treatment was followed by a marked decline in infection prevalence (by PCR) to less than 1%. The decline in prevalence of active disease in children was less marked. Several villages had a prevalence of active trachoma in 1 to 9 year old children of greater than 10% during the follow-up period, mostly in the absence of detectable infection. The implication of this study is that a single, high coverage mass treatment may be sufficient to control C. trachomatis infection in a low prevalence setting, particularly when combined with environmental measures to limit transmission. However, relying on clinical signs to guide treatment decisions is likely to lead to significant amounts of over treatment where current guidelines are implemented.
PMCID: PMC2950148  PMID: 20957147
9.  Integrated monitoring and evaluation and environmental risk factors for urogenital schistosomiasis and active trachoma in Burkina Faso before preventative chemotherapy using sentinel sites 
BMC Infectious Diseases  2011;11:191.
Over 1 billion of the world's poorest inhabitants are afflicted by neglected tropical diseases (NTDs). Integrated control programmes aimed at tackling these debilitating NTDs have been recently initiated, mainly using preventative chemotherapy. Monitoring and evaluation (M&E) of these integrated programs presents particular challenges over and above those required for single disease vertical programmes. We used baseline data from the National NTD Control Programme in Burkina Faso in order to assess the feasibility of an integrated survey design, as well as to elucidate the contribution of environmental variables to the risk of either Schistosoma haematobium, trachoma, or both among school-aged children.
S. haematobium infection was diagnosed by detecting eggs in urine. A trachoma case was defined by the presence of Trachomatous inflammation-Follicular (TF) and/or Trachomatous inflammation-Intense (TI) in either eye. Baseline data collected from 3,324 children aged 7-11 years in 21 sentinel sites across 11 regions of Burkina Faso were analyzed using simple and multivariable hierarchical binomial logistic regression models fitted by Markov Chain Monte Carlo estimation methods. Probabilities of the risk of belonging to each infection/disease category were estimated as a function of age, gender (individual level), and environmental variables (at sentinel site level, interpolated from national meteorological stations).
Overall prevalence at the sentinel sites was 11.79% (95% CI: 10.70-12.89) for S. haematobium; 13.30% (12.14-14.45) for trachoma and 0.84% (0.53-1.15) for co-infections. The only significant predictor of S. haematobium infection was altitude. There were significant negative associations between the prevalence of active trachoma signs and minimum temperature, and air pressure. Conditional upon these predictors, these data are consistent with the two pathogens being independent.
Urogenital schistosomiasis and trachoma constitute public health problems in Burkina Faso. Sentinel site (at school level) surveys for these two NTDs can be implemented simultaneously. However, to support MDA treatment decisions in Burkina Faso, the protocol used in this study would only be applicable to hypoendemic trachoma areas. More research is needed to confirm if these findings can be generalized to West Africa and beyond.
PMCID: PMC3161883  PMID: 21749703
10.  Association between Ocular Bacterial Carriage and Follicular Trachoma Following Mass Azithromycin Distribution in The Gambia 
Trachoma, caused by ocular Chlamydia trachomatis infection, is the leading infectious cause of blindess, but its prevalence is now falling in many countries. As the prevalence falls, an increasing proportion of individuals with clinical signs of follicular trachoma (TF) is not infected with C. trachomatis. A recent study in Tanzania suggested that other bacteria may play a role in the persistence of these clinical signs.
Methodology/Principal Findings
We examined associations between clinical signs of TF and ocular colonization with four pathogens commonly found in the nasopharnyx, three years after the initiation of mass azithromycin distribution. Children aged 0 to 5 years were randomly selected from 16 Gambian communitites. Both eyes of each child were examined and graded for trachoma according to the World Health Organization (WHO) simplified system. Two swabs were taken from the right eye: one swab was processed for polymerase chain reaction (PCR) using the Amplicor test for detection of C. trachomatis DNA and the second swab was processed by routine bacteriology to assay for the presence of viable Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis. Prevalence of TF was 6.2% (96/1538) while prevalence of ocular C. trachomatis infection was 1.0% (16/1538). After adjustment, increased odds of TF were observed in the presence of C. trachomatis (OR = 10.4, 95%CI 1.32–81.2, p = 0.03), S. pneumoniae (OR = 2.14, 95%CI 1.03–4.44, p = 0.04) and H. influenzae (OR = 4.72, 95% CI 1.53–14.5, p = 0.01).
Clinical signs of TF can persist in communities even when ocular C. trachomatis infection has been controlled through mass azithromycin distribution. In these settings, TF may be associated with ocular colonization with bacteria commonly carried in the nasopharnyx. This may affect the interpretation of impact surveys and the determinations of thresholds for discontinuing mass drug administration.
Author Summary
Trachoma, the world's leading infectious cause of blindness, is caused by ocular infection with the bacterium Chlamydia trachomatis. In low-prevalence settings and following mass treatment campaigns, clinically active follicular trachoma (TF) can be found in the absence of C. trachomatis infection. We carried out this study to investigate associations between ocular carriage of non-chlamydial pathogens and a clinical diagnosis of TF following a mass treatment campaign in The Gambia. We found that children who carried Streptococcus pneumoniae or Haemophilus influenza in their eyes were more likely to have been diagnosed with TF than children who did not carry these pathogens. In The Gambia, non-chlamydial pathogens may be inducing or exacerbating TF in the absence of C. trachomatis infection.
PMCID: PMC3723595  PMID: 23936573
11.  The Frequency of Chlamydia trachomatis Major Outer Membrane Protein-Specific CD8+ T Lymphocytes in Active Trachoma Is Associated with Current Ocular Infection  
Infection and Immunity  2006;74(3):1565-1572.
Chlamydia-specific cytotoxic T lymphocytes are able to control model infections but may be implicated in disease pathogenesis. HLA-A2 peptide tetramers to Chlamydia trachomatis major outer membrane protein 258-266 (MOMP258-266) and MOMP260-268 were used to characterize HLA class I-restricted CD8+ T cells in Gambian children aged 4 to 15 years with clinical signs of active trachoma and/or infection with C. trachomatis. The frequencies of circulating HLA-A2 tetramer binding cells (TBC) were determined in whole blood samples by flow cytometric analysis. Initial screening of subjects with an anti-HLA-A2 antibody confirmed the presence of either HLA-A2 or HLA-A28. These were subsequently further divided by molecular subtyping. The C. trachomatis-specific HLA-A2 peptide tetramers were able to bind T cells with receptors from subjects which were restricted by either the HLA-A2 or the HLA-A28 restriction element. In this population, the median value of C. trachomatis-specific CD8+ T cells was 0.02%, with frequencies of up to 3.71% of CD8+ T cells reactive with a single tetramer in a minority of subjects. TBC were detected more often in subjects who were infected at the ocular surface, and their presence was associated with infection episodes of longer duration. Detection of C. trachomatis-specific TBC was not associated with the presence of disease or with the estimated load of ocular C. trachomatis infection at the time of sample collection. High frequencies of C. trachomatis-specific cells did not predict subsequent appearance or resolution of the clinical disease signs of active trachoma.
PMCID: PMC1418621  PMID: 16495527
12.  Prevalence of and Risk Factors for Trachoma in Kano State, Nigeria 
PLoS ONE  2012;7(7):e40421.
In northern Nigeria, trachoma is an important public health problem, but there are currently few population-based data on prevalence of disease and no formal trachoma control programs.
Methodology / Principal Findings
In Kano state, Nigeria, we conducted a population-based cross-sectional survey using multistage cluster random sampling, combining examination for clinical signs of trachoma and application of questionnaires assessing potential household-level risk factors. A total of 4491 people were examined in 40 clusters, of whom 1572 were aged 1–9 years, and 2407 (53.6%) were female. In 1–9 year-olds, the prevalence of trachomatous inflammation–follicular (TF) was 17.5% (95% CI: 15.7–19.5%). In a multivariate model, independent risk factors for active trachoma were the presence of flies on the face (OR 1.98, 95% CI 1.30–3.02); a dirty face (OR 2.45, 95% CI 1.85–3.25) and presence of animal dung within the compound of residence (OR 3.46, 95% CI 1.62–7.41). The prevalence of trachomatous trichiasis in persons aged ≥15years was 10.9% (95% CI: 9.7–12.2%). Trichiasis was significantly more common in adult females than in adult males.
There is an urgent need for a trachoma control program in Kano state, with emphasis given to provision of good quality trichiasis surgery. Particular effort will need to be made to identify women with trichiasis and engage them with appropriate services while also taking steps to secure azithromycin for mass treatment and ensuring personal and environmental hygiene.
PMCID: PMC3391244  PMID: 22792311
13.  Mass Treatment with Azithromycin for Trachoma: When Is One Round Enough? Results from the PRET Trial in The Gambia 
The World Health Organization has recommended three rounds of mass drug administration (MDA) with antibiotics in districts where the prevalence of follicular trachoma (TF) is ≥10% in children aged 1–9 years, with treatment coverage of at least 80%. For districts at 5–10% TF prevalence it was recommended that TF be assessed in 1–9 year olds in each community within the district, with three rounds of MDA provided to any community where TF≥10%. Worldwide, over 40 million people live in districts whose TF prevalence is estimated to be between 5 and 10%. The best way to treat these districts, and the optimum role of testing for infection in deciding whether to initiate or discontinue MDA, are unknown.
In a community randomized trial with a factorial design, we randomly assigned 48 communities in four Gambian districts, in which the prevalence of trachoma was known or suspected to be above 10%, to receive annual mass treatment with expected coverage of 80–89% (“Standard”), or to receive an additional visit in an attempt to achieve coverage of 90% or more (“Enhanced”). The same 48 communities were randomised to receive mass treatment annually for three years (“3×”), or to have treatment discontinued if Chlamydia trachomatis (Ct) infection was not detected in a sample of children in the community after mass treatment (stopping rule(“SR”)). Primary outcomes were the prevalence of TF and of Ct infection in 0–5 year olds at 36 months.
The baseline prevalence of TF and of Ct infection in the target communities was 6.5% and 0.8% respectively. At 36 months the prevalence of TF was 2.8%, and that of Ct infection was 0.5%. No differences were found between the arms in TF or Ct infection prevalence either at baseline (Standard-3×: TF 5.6%, Ct 0.7%; Standard-SR: TF 6.1%, Ct 0.2%; Enhanced-3×: TF 7.4%, Ct 0.9%; and Enhanced-SR: TF 6.2%, Ct 1.2%); or at 36 months (Standard-3×: TF 2.3%, Ct 1.0%; Standard-SR TF 2.5%, Ct 0.2%; Enhanced-3× TF 3.0%, Ct 0.2%; and Enhanced-SR TF 3.2%, Ct 0.7% ). The implementation of the stopping rule led to treatment stopping after one round of MDA in all communities in both SR arms. Mean treatment coverage of children aged 0–9 in communities randomised to standard treatment was 87.7% at baseline and 84.8% and 88.8% at one and two years, respectively. Mean coverage of children in communities randomized to enhanced treatment was 90.0% at baseline and 94.2% and 93.8% at one and two years, respectively. There was no evidence of any difference in TF or Ct prevalence at 36 months resulting from enhanced coverage or from one round of MDA compared to three.
The Gambia is close to the elimination target for active trachoma. In districts prioritised for three MDA rounds, one round of MDA reduced active trachoma to low levels and Ct infection was not detectable in any community. There was no additional benefit to giving two further rounds of MDA. Programmes could save scarce resources by determining when to initiate or to discontinue MDA based on testing for Ct infection, and one round of MDA may be all that is necessary in some settings to reduce TF below the elimination threshold.
Author Summary
Trachoma, which results from infection with a bacterium Chlamydia trachomatis(Ct), is a leading cause of preventable blindness in the world. One of the currently used control methods is mass drug administration (MDA) with azithromycin, which is initiated according to rates of follicular trachoma(TF) in children. This study was a clinical trial done to determine whether testing communities for Ct infection will prevent unnecessary rounds of MDA. This was done by allowing communities to stop treatment if their infection had been reduced below a threshold. The study compared the effects of one round of mass treatment to three and found that there was no difference in either follicular trachoma or infection rates after three years. One round of treatment reduced TF to a low level. Tests for infection could be used to decide when to start or discontinue MDA and to prevent unnecessary treatment rounds in settings like The Gambia.
PMCID: PMC3681669  PMID: 23785525
14.  What Is Causing Active Trachoma? The Role of Nonchlamydial Bacterial Pathogens in a Low Prevalence Setting 
Active trachoma in a low prevalence setting was associated with nonchlamydial bacterial infection but not Chlamydia trachomatis. This may partly explain the persistence of clinical signs in formally endemic communities.
In low prevalence settings, clinically active follicular trachoma (TF) is often found in the absence of detectable Chlamydia trachomatis. The reasons for this persistent follicular phenotype are not well understood; one possible explanation is that other bacterial species are provoking the inflammatory response. This study investigated the relationship between TF, C. trachomatis, and nonchlamydial bacterial infection.
A cross-sectional survey was conducted in a trachoma endemic village in Tanzania. All available children were examined for trachoma and swabs were collected for microbiologic culture (blood and chocolate agar) and C. trachomatis PCR (Amplicor).
Four hundred seventy-three children under 10 years of age were recruited for this study. The prevalences of TF and C. trachomatis were 13.7% and 5.3%, respectively, and were not associated. Bacteria were cultured from 305 (64.5%) swab samples; 162 (34.3%) grew a pathogen (with or without a commensal organism) and 143 (30.2%) grew commensal bacteria only. The most common pathogens were Streptococcus pneumoniae and Haemophilus influenzae (type B and non–type B). The presence of bacterial pathogens was associated with TF (odds ratio, 4.68; 95% confidence interval, 2.31–9.50; P < 0.001).
In regions with low levels of endemic trachoma, it is possible that much of the TF that is observed is attributable to nonchlamydial bacterial pathogens. It is plausible that individuals who have previously developed a follicular conjunctivitis in response to C. trachomatis may more readily reform conjunctival follicles when challenged with certain other bacterial species.
PMCID: PMC3176035  PMID: 21693601
15.  Clinical and Microbiological Assessment of Trachoma in the Kolofata Health District, Far North Region, Cameroon 
Tropical Medicine and Health  2012;40(1):7-14.
Background and aims: Trachoma is a sight-threatening process triggered by the infection of the conjunctiva with Chlamydiae. Blindness associated with trachoma was reported in Sahelian areas of Cameroon. However, data on the prevalence of this neglected infection in the Far North Region are not available. The aim of this study was a) to assess clinical trachoma and b) to detect Chlamydia in the conjunctiva of trachomatous populations living in the Far North Regions of Cameroon.
Methods: A total of 2,423 randomly selected children (1–10 years) and 1,590 women over 14 from randomly selected villages from the Kolofata Health District (115,000 inhabitants) were included in a cross-sectional study in February 2009. Trained staff examined and obtained conjunctival swabs from trachomatous subjects. DNA was extracted and amplified to detect Chlamydia DNA by real-time PCR. The quality of sampling was assessed by quantifying the number of epithelial cells.
Results: Children (2,397 or 98.9% of the predicted number) and women (1,543; 97.0%) were examined. The prevalence of follicular trachoma (TF) in children was 21% (95% CI 17.8–24.5) and of intense inflammatory trachoma (TI) 5.2% (95% CI 3.6–7.3). Among the women, trichiasis (TT) was observed in 3.4% (95% CI 2.4–4.7), corneal opacities (CO) in 1.4% (95% CI 0.8–2.3) and trachoma-related blindness in 0.9% (95% CI 0.4–1.8). Conditions related to income, illiteracy, latrines, water supply and animals wandering close to dwellings were similar in all the villages. PCR was positive in 35% of children with active trachoma and in 6% of adult females presenting TT and/or related corneal opacities.
Conclusion: The prevalence of trachoma and the severe trachoma sequelae found during this survey underline the urgent need to implement efficient blindness prevention interventions to improve the visual future of the people in the Sahelian region.
PMCID: PMC3426829  PMID: 22949801
trachoma; survey; trichiasis; blindness; Cameroon; Sahel; Kolofata; Chlamydia
16.  Conjunctival Transcriptome in Scarring Trachoma▿ †  
Infection and Immunity  2010;79(1):499-511.
Trachoma is a poorly understood immunofibrogenic disease process, initiated by Chlamydia trachomatis. Differences in conjunctival gene expression profiles between Ethiopians with trachomatous trichiasis (with [TTI] or without [TT] inflammation) and controls (C) were investigated to identify relevant host responses. Tarsal conjunctival swab samples were collected for RNA isolation and C. trachomatis PCR. Transcriptome-wide microarray experiments were conducted on 42 samples (TTI, n = 13; TT, n = 15; C, n =14). Specific results were confirmed by using multiplex quantitative reverse transcription-PCR for 16 mRNA targets in an independent collection of case-control samples: 386 case-control pairs (TTI, n = 244; TT, n = 142; C, n = 386). The gene expression profiles of cases were consistent with squamous metaplasia (keratins, SPRR), proinflammatory cytokine production (IL1β, CXCL5, and S100A7), and tissue remodeling (MMP7, MMP9, MMP12, and HAS3). There was no difference in the level of IFNγ between cases and controls. However, cases had increased INDO, NOS2A, and IL13RA2 and reduced IL13. C. trachomatis was detected in 1/772. Cases show evidence of ongoing inflammation and tissue remodeling, which were more marked where clinical inflammation was also present. Significantly, these processes appear to be active in the absence of current C. trachomatis infection. There was limited evidence of a TH1 response (INDO and NOS2A) and no association between a TH2 response and cases. The epithelium appears to be actively involved in late cicatricial stages of trachoma through the production of proinflammatory factors (IL1β, CXCL5, and S100A7). Longitudinal studies are needed to investigate which etiological factors and pathways are associated with progressive scarring and whether simply controlling chlamydial infection will halt progression in people with established cicatricial disease.
PMCID: PMC3019920  PMID: 20937763
17.  Behavioral activation-based guided self-help treatment administered through a smartphone application: study protocol for a randomized controlled trial 
Trials  2012;13:62.
The need for cost-effective interventions for people suffering from major depressive disorders is essential. Behavioral activation is an intervention that can largely benefit from the use of new mobile technologies (for example smartphones). Therefore, developing smartphone-based behavioral activation interventions might be a way to develop cost-effective treatments for people suffering from major depressive disorders. The aim of this study will be to test the effects of a smartphone-delivered behavioral activation treatment.
The study will be a randomized controlled trial with a sample size of 120 participants, with 60 patients in each group. The treatment group includes an 8-week smartphone-based behavioral activation intervention, with minimal therapist contact. The smartphone-based intervention consists of a web-based psychoeducation, and a smartphone application. There is also a back-end system where the therapist can see reports from the patients or activities being reported. In the attention control group, we will include brief online education and then recommend use of a smartphone application that is not directly aimed at depression (for example, ‘Effective meditation’). The duration of the control condition will also be 8 weeks. For ethical reasons we will give the participants in the control group access to the behavioral activation treatment following the 8-week treatment period.
We believe that this trial has at least three important implications. First, we believe that smartphones can be integrated even further into society and therefore may serve an important role in health care. Second, while behavioral activation is a psychological treatment approach for which there is empirical support, the use of a smartphone application could serve as the therapist’s prolonged arm into the daily life of the patient. Third, as we have been doing trials on guided Internet treatment for more than 10 years it is now time to move to the next generation of information technology - smartphones - which are not only relevant for Swedish conditions but also for developing countries in the world which are increasingly empowered by mobile phones with Internet connection.
Trial registration NCT01463020
PMCID: PMC3404948  PMID: 22607302
Depression; Behavioral activation; Smartphone application; Cost-effectiveness; Randomized; Controlled trial
18.  The Effect of Multiple Rounds of Mass Drug Administration on the Association between Ocular Chlamydia trachomatis Infection and Follicular Trachoma in Preschool-Aged Children 
To examine the relationship between ocular Chlamydia trachomatis infection and follicular trachoma (TF) in children prior to and following multiple rounds of annual mass drug administration (MDA) with azithromycin.
Methodology/principal findings
Thirty-two communities with endemic trachoma in Kongwa District, Tanzania, were offered annual MDA as part of a district-wide trachoma control program. Presence of ocular C. trachomatis infection and TF were assessed in 3,200 randomly sampled children aged five years and younger, who were examined prior to each MDA. Infection was detected using the Amplicor CT/NG assay and TF was identified by clinical examination using the World Health Organization (WHO) simplified grading system. The association between chlamydial infection and TF in children was evaluated at baseline prior to any treatment, and 12 months after each of three annual rounds of mass treatment. Factors associated with infection were examined using generalized estimating equation models.
At baseline, the overall prevalence of chlamydial infection and TF was 22% and 31%, respectively. Among children with clinical signs of TF, the proportion of those with infection was 49% prior to treatment and declined to 30% after three MDAs. The odds of infection positivity among children with clinical signs of TF decreased by 26% (OR 0.74, 95% CI 0.65 to 0.84, p = <0.01) with each MDA, after adjusting for age. For children aged under one year, who did not receive treatment, the relationship was unchanged.
The association between ocular C. trachomatis infection and TF weakened in children with each MDA, as both infection and clinical disease prevalence declined. However, there was still a significant proportion of TF cases with infection after three rounds of MDA. New strategies are needed to assess this residual infection for optimal treatment distribution.
Author Summary
Trachoma, which is caused by infection by the bacterium Chlamydia trachomatis, is the leading preventable cause of blindness worldwide. Annual mass drug administration with azithromycin is recommended for trachoma control; however, monitoring the impact of azithromycin, which targets C. trachomatis, relies on the clinical assessment of follicular trachoma. If the relationship between chlamydial infection and the presence or absence of follicular trachoma were to remain unchanged with each round of treatment, we would be able to predict the level of residual infection, and the need for additional treatment, from the prevalence of follicular trachoma. In this study, we examined the association between infection and presence or absence of follicular trachoma in children prior to and following multiple rounds of treatment. Findings suggest that with increasing rounds of treatment, the prevalence of infection declines in children both with and without signs of follicular trachoma. Newer strategies, including tests that can rapidly detect infection under field conditions, may be needed to assess residual infection in treated communities.
PMCID: PMC3983082  PMID: 24722392
19.  CT694 and pgp3 as Serological Tools for Monitoring Trachoma Programs 
Defining endpoints for trachoma programs can be a challenge as clinical signs of infection may persist in the absence of detectable bacteria. Antibody-based tests may provide an alternative testing strategy for surveillance during terminal phases of the program. Antibody-based assays, in particular ELISAs, have been shown to be useful to document C. trachomatis genital infections, but have not been explored extensively for ocular C. trachomatis infections.
Methodology/Principal Findings
An antibody-based multiplex assay was used to test two C. trachomatis antigens, pgp3 and CT694, for detection of trachoma antibodies in bloodspots from Tanzanian children (n = 160) collected after multiple rounds of mass azithromycin treatment. Using samples from C. trachomatis-positive (by PCR) children from Tanzania (n = 11) and control sera from a non-endemic group of U.S. children (n = 122), IgG responses to both pgp3 and CT694 were determined to be 91% sensitive and 98% specific. Antibody responses of Tanzanian children were analyzed with regard to clinical trachoma, PCR positivity, and age. In general, children with more intense ocular pathology (TF/TI = 2 or most severe) had a higher median antibody response to pgp3 (p = 0.0041) and CT694 (p = 0.0282) than those with normal exams (TF/TI = 0). However, 44% of children with no ocular pathology tested positive for antibody, suggesting prior infection. The median titer of antibody responses for children less than three years of age was significantly lower than those of older children. (p<0.0001 for both antigens).
The antibody-based multiplex assay is a sensitive and specific additional tool for evaluating trachoma transmission. The assay can also be expanded to include antigens representing different diseases, allowing for a robust assay for monitoring across NTD programs.
Author Summary
Trachoma is an ocular disease caused by repeated infections with the bacteria Chlamydia trachomatis that is observed mostly in children and women. Scarring after repeated infections causes eyelashes to turn under the lid, possibly leading to corneal opacity and blindness. Efforts have increased by multiple organizations to meet the World Health Organization's goal of eliminating trachoma by 2020. As mass drug administration is carried out, it can be difficult to assess whether transmission has lessened enough to stop treatment without resurgence of disease. In this low prevalence setting, sensitive and specific surveillance tools are important. Currently, clinical diagnosis is carried out by examination of the inside of the eyelid for follicles and inflammation, and infection is best assessed using PCR analysis with commercial kits. These test results do not always align, indicating a need for additional tools for surveillance. Using the multiplex assay platform, we compared antibody responses to two chlamydial antigens with eye exams and PCR results of 160 Tanzanian children participating in a mass treatment program. Antibody responses were shown to be a good indicator of infection and disease status and antibody tests may be useful as surveillance tools.
PMCID: PMC3486877  PMID: 23133684
20.  Longitudinal analysis of antibody responses to trachoma antigens before and after mass drug administration 
BMC Infectious Diseases  2014;14:216.
Blinding trachoma, caused by the bacteria Chlamydia trachomatis, is a neglected tropical disease targeted for elimination by 2020. A major component of the elimination strategy is mass drug administration (MDA) with azithromycin. Currently, program decisions are made based on clinical signs of ocular infection, but we have been investigating the use of antibody responses for post-MDA surveillance. In a previous study, IgG responses were detected in children lacking clinical evidence of trachoma, suggesting that IgG responses represented historical infection. To explore the utility of serology for program evaluation, we compared IgG and IgA responses to trachoma antigens and examined changes in IgG and IgA post-drug treatment.
Dried blood spots and ocular swabs were collected with parental consent from 264 1–6 year olds in a single village of Kongwa District, central Tanzania. Each child also received an ocular exam for detection of clinical signs of trachoma. MDA was given, and six months later an additional blood spot was taken from these same children. Ocular swabs were analyzed for C. trachomatis DNA and antibody responses for IgA and total IgG were measured in dried bloods spots.
Baseline antibody responses showed an increase in antibody levels with age. By age 6, the percentage positive for IgG (96.0%) was much higher than for IgA (74.2%). Antibody responses to trachoma antigens declined significantly six months after drug treatment for most age groups. The percentage decrease in IgA response was much greater than for IgG. However, no instances of seroreversion were observed.
Data presented here suggest that focusing on concordant antibody responses in children will provide the best serological surveillance strategy for evaluation of trachoma control programs.
PMCID: PMC4016634  PMID: 24755001
21.  Trachoma Prevalence and Associated Risk Factors in The Gambia and Tanzania: Baseline Results of a Cluster Randomised Controlled Trial 
Blinding trachoma, caused by ocular infection with Chlamydia trachomatis, is targeted for global elimination by 2020. Knowledge of risk factors can help target control interventions.
Methodology/Principal Findings
As part of a cluster randomised controlled trial, we assessed the baseline prevalence of, and risk factors for, active trachoma and ocular C. trachomatis infection in randomly selected children aged 0–5 years from 48 Gambian and 36 Tanzanian communities. Both children's eyes were examined according to the World Health Organization (WHO) simplified grading system, and an ocular swab was taken from each child's right eye and processed by Amplicor polymerase chain reaction to test for the presence of C. trachomatis DNA. Prevalence of active trachoma was 6.7% (335/5033) in The Gambia and 32.3% (1008/3122) in Tanzania. The countries' corresponding Amplicor positive prevalences were 0.8% and 21.9%. After adjustment, risk factors for follicular trachoma (TF) in both countries were ocular or nasal discharge, a low level of household head education, and being aged ≥1 year. Additional risk factors in Tanzania were flies on the child's face, being Amplicor positive, and crowding (the number of children per household). The risk factors for being Amplicor positive in Tanzania were similar to those for TF, with the exclusion of flies and crowding. In The Gambia, only ocular discharge was associated with being Amplicor positive.
These results indicate that although the prevalence of active trachoma and Amplicor positives were very different between the two countries, the risk factors for active trachoma were similar but those for being Amplicor positive were different. The lack of an association between being Amplicor positive and TF in The Gambia highlights the poor correlation between the presence of trachoma clinical signs and evidence of C. trachomatis infection in this setting. Only ocular discharge was associated with evidence of C. trachomatis DNA in The Gambia, suggesting that at this low endemicity, this may be the most important risk factor.
Trial Registration NCT00792922
Author Summary
Trachoma is caused by Chlamydia trachomatis and is the leading infectious cause of blindness. The World Health Organization's (WHO) control strategy includes antibiotic treatment of all community members, facial cleanliness, and environmental improvements. By determining how prevalent trachoma is, decisions can be made whether control activities need to be put in place. Knowing what factors make people more at risk of having trachoma can help target trachoma control efforts to those most at risk. We looked at the prevalence of active trachoma and C. trachomatis infection in the eyes of children aged 0–5 years in The Gambia and Tanzania. We also measured risk factors associated with having active trachoma or infection. The prevalence of both active trachoma and infection was lower in The Gambia (6.7% and 0.8%, respectively) than in Tanzania (32.3% and 21.9%, respectively). Risk factors for active trachoma were similar in the two countries. For infection, the risk factors in Tanzania were similar to those for TF, whereas in The Gambia, only ocular discharge was associated with infection. These results show that although the prevalence of active trachoma and infection is very different between the two countries, the risk factors for active trachoma are similar but those for infection are different.
PMCID: PMC2970530  PMID: 21072224
22.  Prevalence of Active Trachoma Two Years after Control Activities 
Ghana Medical Journal  2009;43(2):54-60.
Following an epidemiological assessment to map out the endemicity of trachoma in Ghana, Trachoma control interventions were put in place in two districts in Upper West and three in Northern Regions in the year 2001. The control activities were based on the WHO recommended strategy of SAFE. After two years of intervention, a study was undertaken to determine the impact of the control activities.
A simple random selection of compounds was done. Trained and standardized ophthalmic nurses examined children aged 1 to 10 years for dirty faces and signs of active trachoma. Community members were interviewed to ascertain availability of potable water and latrines.
A total of 9,288 children aged 1–10 years were examined in 2003. Overall TF/TI prevalence for Upper West was 5.6% and for Northern Region was 3.5%. In 2000, 6,241 children aged 1–10 years were examined. The overall prevalence of TF/TI for baseline was 15.0% for Upper West and 9.1% for Northern Region. The prevalence of TF/TI showed significant reduction (p-value <0.001) in all five districts and overall in the two regions.
Trachoma control activities over a two-year period in two regions in Ghana had led to significant reduction in the prevalence of active disease. Integrated surveillance and active monitoring will help early detection of active disease.
PMCID: PMC3039232  PMID: 21326842
Active Trachoma; Prevalence; SAFE Strategy; Intervention; Impact
23.  Active Trachoma Is Associated with Increased Conjunctival Expression of IL17A and Profibrotic Cytokines▿† 
Infection and Immunity  2011;79(12):4977-4983.
The immunological basis of scarring trachoma is not well understood. It is unclear whether it is driven primarily through cell-mediated adaptive or epithelial-cell-derived innate responses. The purpose of this study was to investigate the expression of the inflammatory and fibrogenic mediators which may be involved. We conducted a cross-sectional survey of children living in an untreated trachoma-endemic community in Tanzania. The children were examined for signs of trachoma, and swabs were collected for bacteriological culture and RNA and DNA isolation. Chlamydia trachomatis was detected by the Amplicor PCR test. The expression of the following genes was measured by quantitative reverse transcription-PCR (RT-PCR): S100A7, IL1B, IL17A, IL23A, CXCL5, CCL18, TLR2, NLRP3, KLRD1, CTGF, and MMP9. Four hundred seventy children under the age of 10 years were included. Follicular trachoma (TF) was detected in 65 children (14%), C. trachomatis was detected in 25 (5%), and bacterial pathogens were cultured in 161 (34%). TF was associated with significantly increased expression of S100A7, IL17A, CCL18, CXCL5, and CTGF. Expression was increased further in the presence of papillary inflammation. Nonchlamydial bacterial infection was associated with increased expression of IL17A, CXCL5, CCL18, and KLRD1. IL17A expression was associated with increased expression of S100A7, CXCL5, CCL18, KLRD1, and CTGF. These data are consistent with a role for IL-17A in orchestrating the proinflammatory response in trachoma. Its activity may be promoted either as part of the cell-mediated response or through innate pathways. It may drive a range of proinflammatory factors leading to excessive tissue damage and repair involving fibrosis.
PMCID: PMC3232643  PMID: 21911461
24.  Comparative sensitivity of fluorescent antibody staining of conjunctival scrapings and irradiated McCoy cell culture for the diagnosis of hyperendemic trachoma. 
The sensitivity of an indirect fluorescent antibody (FA) staining technique for detecting chlamydial inclusions in scrapings from the whole conjunctiva (upper tarsus, upper fornix, and lower lid) was compared with the sensitivity of culture in irradiated McCoy cells for the diagnosis of hyperendemic trachoma. In a group of 211 patients with various grades of active trachoma from the Bandar Abbas area of Southern Iran 42 patients were positive for chlamydiae by either method. There was little difference between the rates of positivity of FA staining of the scrapings from the whole conjunctiva (28 positives) and culture in irradiated McCoy cells (32 positives). In the patients included in this study chlamydial inclusions were detected in 15 eyes by examination of FA stained scrapings taken from the upper tarsal conjunctiva, whereas inclusions were detected in 40 eyes by the additional examination of scrapings taken from the upper fornix and lower lid (P less than 0.001). The examination of FA stained scrapings taken from the whole conjunctiva and spread as a single but larger smear may provide a satisfactory alternative to cell culture methods for the diagnosis of trachoma, particularly for field studies when cell culture facilities are not available.
PMCID: PMC1043669  PMID: 6992855
25.  Trachoma 
BMJ Clinical Evidence  2007;2007:0706.
Active trachoma is caused by chronic infection of the conjunctiva by Chlamydia trachomatis, and is the world's leading infectious cause of blindness. Infection can lead to scarring of the tarsal conjunctiva, inversion of the eyelashes so that they abrade the cornea (trichiasis), and corneal opacity, leading to blindness. Trachoma is a disease of poverty, overcrowding, and poor sanitation. Active disease affects mainly children, but adults are at increased risk of scarring.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent scarring trachoma by reducing the prevalence of active trachoma? What are the effects of eye lid surgery for entropion and trichiasis? We searched: Medline, Embase, The Cochrane Library and other important databases up to January 2006 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 23 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, face washing (alone or plus topical tetracycline), fly control (through the provision of pit latrines, and using insecticide), health education, and lid surgery (bilamellar tarsal rotation, or tarsal advance and rotation).
Key Points
Active trachoma is caused by chronic infection of the conjunctiva by Chlamydia trachomatis, and is the world's leading infectious cause of blindness. Infection can lead to scarring of the tarsal conjunctiva, shortening and inversion of the upper eyelid (entropion) and scarring of the eye by eyelashes (trichiasis), leading to blindness.Trachoma is a disease of poverty, overcrowding, and poor sanitation. Active disease mainly affects children, but adults are at increased risk of scarring.
Public health interventions to improve hygiene may reduce the risks of developing trachoma, but studies have given conflicting results. Face washing plus topical antibiotics may be beneficial, but we don't know whether face washing alone is effective.Fly control using insecticide alone, insecticide plus mass antibiotics, or by providing pit latrines, may reduce the risks of trachoma, but is unlikely to be a feasible large-scale approach.
We don't know whether oral or topical antibiotics reduce the risk of active trachoma compared with placebo or with each other, as few comparable studies have been found.
Lid rotation surgery with bilamellar tarsal rotation or tarsal advance and rotation may be effective at correcting entropion and trichiasis compared with other types of surgery.
We don't know whether posterior lamellar tarsal rotation plus azithromycin is more effective than posterior lamellar tarsal rotation alone at correcting entropion and trichiasis.
PMCID: PMC2943797  PMID: 19450349

Results 1-25 (884833)