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Corneal ulcers are a common cause of blindness in low-income and middle-income countries, usually resulting from traumatic corneal abrasions during agricultural work. Antimicrobial prophylaxis of corneal abrasions can help prevent corneal ulcers, but delays in the initiation of therapy are frequent. We aimed to assess whether a community-based programme for corneal ulcer prevention would reduce the incidence of corneal ulceration.A cluster-randomised trial was performed in village development committees (VDCs) in Nepal. VDCs in the catchment area of Bharatpur Eye Hospital, Nepal with less than 15 000 people were eligible for inclusion. We randomly assigned (1:1) VDCs to either an intervention group or a control group. In the intervention VDCs, existing female community health volunteers (FCHVs) were trained to diagnose corneal abrasions and provide a 3-day course of ophthalmic antimicrobials to their patients. In the control VDCs, FCHVs did not provide this intervention. Participants were not masked given the nature of the intervention. Both groups were followed up for 3 years for photographic evidence of corneal ulceration. The primary outcome was the incidence of corneal ulceration, determined by masked assessment of corneal photographs. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01969786.We assessed 112 VDCs, of which 24 were enrolled. The study was performed between Feb 4, 2014, and Oct 20, 2017. 12 VDCs were randomly assigned to the intervention group and 12 to the control group. 252 539 individuals were included in the study (130 579 in the intervention group and 121 960 in the control group). FCHVs diagnosed and provided antimicrobials for 4777 corneal abrasions. The census identified 289 corneal ulcers among 246 893 person-years in the intervention group (incidence 1·21 cases [95% CI 0·85-1·74] per 1000 person-years) and 262 corneal ulcers among 239 170 person-years in the control group (incidence 1·18 cases [0·82-1·70] per 1000 person-years; incidence rate ratio 1·03 [95% CI 0·63-1·67]; p=0·93). Medication allergy was self-reported in 0·2% of participants.We did not detect a reduction in the incidence of corneal ulceration during the first 3 years of a community-based corneal ulcer prevention programme. Further study might be warranted in more rural areas where basic eye care facilities are not available.National Eye Institute.

Objective To determine the relationship between visual impairment and other disabilities in a developing country. Methods In this cross-sectional ancillary study, all individuals 50 years and older in 18 communities in the Chitwan region of Nepal were administered visual acuity screening and the Washington Group Short Set (WGSS) of questions on disability. The WGSS elicits a 4-level response for six disability domains: vision, hearing, walking/climbing, memory/concentration, washing/dressing, and communication. The association between visual impairment and disability was assessed with age- and sex-adjusted logistic regression models. Results Overall, 4719 of 4726 individuals successfully completed visual acuity and disability screening. Median age of participants was 61 years (interquartile range: 55-69 years), and 2449 (51.9%) were female. Participants with vision worse than 6/60 in the better-seeing eye were significantly more likely to be classified as having a disability in vision (OR 18.4, 95% CI 9.9-33.5), walking (OR 5.3, 95% CI 2.9-9.1), washing (OR 9.4, 95% CI 4.0-21.1), and communication (OR 5.0, 95% CI 1.7-13.0), but not in hearing (OR 0.6, 95% CI 0.006-2.2) or memory (OR 2.2, 95% CI 0.7-5.1). Conclusions Visually impaired participants were more likely to self-report disabilities, though causality could not be ascertained. Public health programs designed to reduce visual impairment could use the WGSS to determine unintended benefits of their interventions.

Previous studies have used subjective assessments to implicate darker skin color as a risk factor for glaucoma. This study used objective measurements to determine whether skin melanin is a risk fa...

Purpose: To estimate the prevalence and causes of blindness (BL), severe visual impairment (SVI), moderate visual impairment (ModVI) and mild visual impairment (MildVI) in children in Narayani Zone, Nepal. Methods: In 2017, 100 population clusters within the Narayani Zone of Nepal were selected using RAAB software. Children (aged 0-15 years) suspected of having visual problems were identified using Key Informants (KIs) and school teachers and were referred for ophthalmologic examination. Eye care staff actively sought children who failed to present for examination. Causes of BL/SVI/ModVI/MildVI were categorized using standard World Health Organization definitions. Results: Of 76,588 children selected, 72,900 (95%) were screened. Of 2,158 children referred for examination, 1,322 were referred by teachers and 836 by KIs. A total of 1,617 (75%) children received a detailed examination, of whom 128 children [65 girls (51%)] mean age of 9.4 (± 4.1 years) were confirmed to have BL 7 (5.5%), SVI 16 (12.5%), ModVI 19 (15%) or MildVI 86 (67%). The combined prevalence of BL/SVI/ModVI/MildVI was 175/100,000 (95% CI 172-178/100,000); BL/SVI/ModVI was 55/100,000 (95% CI 53-57/100,000) and the combined BL/SVI estimate was 30/100,000 (95% CI 29-31/100,000). The leading causes of BL/SVI/MVI were refractive error 23 (55%) and whole globe disorders 5 (12%). Total avoidable causes were 31 (74%). Conclusion: The prevalence of BL/SVI/ModVI among children in Narayani Zone was moderate and included a high proportion of avoidable and treatable cases. Pediatric ophthalmic services need improvement, mainly refractive error correction in rural areas of Nepal.

Background/aimsWe aimed to examine risk factors for corneal ulcer in a rural and peri-urban setting in Nepal.MethodsThis population-based matched case–control study was nested in a cluster randomised trial in 24 village development committees in Nepal. Incidence density sampling was used to match incident corneal opacity cases to controls, matching on time of opacity, age, sex and location. Cases and controls were invited to participate in a survey of risk factors for corneal ulcer. Risk factors were evaluated using conditional logistic regression to account for matching.ResultsOf the 540 participants with incident opacities identified in the trial, 433 were willing to participate in this substudy and matched to a control. Compared with controls, cases had lower odds of having any education vs no education (adjusted OR, aOR 0.60, 95% CI 0.39 to 0.94), working in non-manual labour occupations vs manual labour occupations (aOR 0.64, 95% CI 0.42 to 0.95) and preferring medical shops for ocular trauma versus eye care system centres (aOR 0.58, 95% CI 0.37 to 0.92). Cases had higher odds of protective goggle use versus no protection (aOR 3.8, 95% CI 1.3 to 11.0) and having an ocular injury vs none (aOR 7.7, 95% CI 4.3 to 13.6) compared with controls.ConclusionWe found ocular injury, manual labour and lower education to be strongly associated with the development of corneal ulcer. Given the persistent burden of corneal blindness in this area, prevention efforts could target efforts to increase access to care in areas where these factors are common.

IntroductionThe majority of blindness worldwide could be prevented or reversed with early diagnosis and treatment, yet identifying at-risk and prevalent cases of eye disease and linking them with care remain important obstacles to addressing this burden. Leading causes of blindness like glaucoma, diabetic retinopathy and age-related macular degeneration have detectable early asymptomatic phases and can cause irreversible vision loss. Mass screening for such diseases could reduce visual impairment at the population level.Methods and analysisThis protocol describes a parallel-group cluster-randomised trial designed to determine whether community-based screening for glaucoma, diabetic retinopathy and age-related macular degeneration reduces population-level visual impairment in Nepal. A door-to-door population census is conducted in all study communities. All adults aged ≥60 years have visual acuity tested at the census visit, and those meeting referral criteria are referred to a local eye care facility for further diagnosis and management. Communities are subsequently randomised to a community-based screening programme or to no additional intervention. The intervention consists of a single round of screening including intraocular pressure and optical coherence tomography assessment of all adults ≥60 years old with enhanced linkage to care for participants meeting referral criteria. Four years after implementation of the intervention, masked outcome assessors conduct a repeat census to collect data on the primary outcome, visual acuity. Individuals with incident visual impairment receive a comprehensive ophthalmological examination to determine the cause of visual impairment. Outcomes are compared by treatment arm according to the originally assigned intervention.Ethics and disseminationThe trial has received ethical approval from the University of California San Francisco Institutional Review Board, Nepal Netra Jyoti Sangh and the Nepal Health Research Council. Results of this trial will be disseminated through publication in peer-reviewed journals and presentation at local and international meetings.Trial registration numberNCT03752840

Medical shops in Nepal are a main point of treatment for many diseases including ophthalmic conditions. We sought to evaluate pharmaceutical shop worker knowledge of corneal ulcers and abrasions. A pharmaceutical shop worker from each of 117 different pharmacies surrounding Bharatpur, Nepal, was presented four different eye photographs (i.e., corneal ulcer, corneal abrasion, conjunctivitis, and a normal eye) and asked about diagnosis and management. Of 117 participants, 86 (74%) identified conjunctivitis correctly but few were able to identify corneal abrasion (50/117; 43%) or corneal infection (47/117; 40%). When presented with an illustrated diagram of potential medications to dispense, 15 (13%) participants chose a topical medication containing a corticosteroid for the corneal abrasion and 25 (21%) did so for the corneal ulcer. The appropriate use of corticosteroids for external eye infections is an important topic for additional training, given the potential for these medications to worsen corneal abrasions and ulcers.

BackgroundThe 1981 Nepal Blindness Survey first identified the Narayani Zone as one of the regions with the highest prevalence of blindness in the country. Subseuqently, a 2006 survey of the Rautahat District of the Narayani Zone found it to have the country’s highest blindness prevalence. This study examines the impact on blind avoidable and treatable eye conditions in this region after significant increase in eye care services in the past decade.MethodsThe rapid assessment of avoidable blindness (RAAB) methodology was used with mobile data collection using the mRAAB smartphone app. Data analysis was done using the standard RAAB software. Based on the 2011 census, 100 clusters of 50 participants aged 50 years or older were randomly sampled proportional to population size.ResultsOf the 5000 participants surveyed, 4771 (95.4%) were examined. The age-adjusted and sex-adjusted prevalence of bilateral blindness, severe visual impairment (SVI) and moderate visual impairment (MVI) were 1.2% (95% CI 0.9% to 1.5%), 2.5% (95% CI 2.0% to -3.0%) and 13.2% (95% CI 11.8% to 14.5%), respectively. Cataract remains the primary cause of blindness and SVI despite cataract surgery coverage (CSC) of 91.5% for VAConclusionThe prevalence of blindness in people over the age of 50 years has decreased from 6.9% in 2006 to 1.2%, a level in keeping with the national average; however, significant gender inequity persists. CSC has improved but continues to favour men.

IntroductionCorneal opacity is a leading cause of blindness worldwide. In resource-limited settings, untreated traumatic corneal abrasions may result in infection and ultimately, opacity. Although antimicrobial treatment of corneal ulcers may successfully cure infections, the scarring that accompanies the resolution of infection can still result in visual impairment. Prevention may be the optimal approach for reducing corneal blindness. Studies have employed community health workers to provide prompt administration of antimicrobials after corneal abrasions to prevent infections, but these studies were not designed to determine the effectiveness of such a programme.Methods and analysisThe Village-Integrated Eye Worker trial (VIEW) is a cluster-randomised trial designed to assess the effectiveness of a community health worker intervention to prevent corneal ulcers. Twenty-four Village Development Committees (VDCs) in Nepal were randomised to receive a corneal ulcer prevention programme or to no intervention. Female Community Health Volunteers (FCHVs) in intervention VDCs are trained to diagnose corneal abrasions, provide antimicrobials and to refer participants when needed. An annual census is conducted over 3 years in all study VDCs to assess the incidence of corneal ulceration via corneal photography (primary outcome). Masked outcome assessors grade corneal photographs to determine the presence or absence of incident corneal opacities. The primary analysis is negative binomial regression to compare the incidence of corneal ulceration by study arm.Ethics and disseminationThe University of California San Francisco Committee on Human Research, Nepal Netra Jyoti Sangh and the Nepal Health Research Council have given ethical approval for the trial. The results of this trial will be presented at local and international meetings and submitted to peer-reviewed journals for publication.Trial registration numberNCT01969786; Pre-results.

The target end date for the global elimination of trachoma as a public health problem is 2020. As countries begin the process for submitting their dossier for the validation of elimination of trachoma as a public health problem, strategies for post-validation surveillance must be considered. Seroprevalence of antibodies against antigens from the causative bacteria Chlamydia trachomatis (Ct) in young children has been shown to reflect trachomatous inflammation-follicular (TF) rates in both endemic and previously endemic settings. However, none of these studies has directly compared age seroprevalence in the same communities before and after mass drug administration (MDA) for trachoma. Here we report a marked shift in age seroprevalence curves in four villages in Kapilvastu District, Nepal, before and after MDA. Clinical examinations were performed and blood was taken before (N = 659) and 5 years after (N = 646) MDA. Rates of TF decreased from 17.6% in ≤ 9-year-olds before MDA (N = 52) to 0% in ≤ 9-year-olds (N = 73) after MDA. Positive antibody responses to Ct in the entire population decreased from 82.1% pre-MDA to 35.8% post-MDA, whereas those among ≤ 9-year-olds decreased from 59.6% to 4.1%. These data show that the postintervention decrease in TF was reflected in a drop in anti-Ct antibody responses, suggesting that antibody responses could be useful indicators for post-validation surveillance.

The target end date for the global elimination of trachoma as a public health problem is 2020. As countries begin the process for submitting their dossier for the validation of elimination of trachoma as a public health problem, strategies for post-validation surveillance must be considered. Seroprevalence of antibodies against antigens from the causative bacteria Chlamydia trachomatis (Ct) in young children has been shown to reflect trachomatous inflammation–follicular (TF) rates in both endemic and previously endemic settings. However, none of these studies has directly compared age seroprevalence in the same communities before and after mass drug administration (MDA) for trachoma. Here we report a marked shift in age seroprevalence curves in four villages in Kapilvastu District, Nepal, before and after MDA. Clinical examinations were performed and blood was taken before (N = 659) and 5 years after (N = 646) MDA. Rates of TF decreased from 17.6% in ≤ 9-year-olds before MDA (N = 52) to 0% in ≤ 9-year-olds (N = 73) after MDA. Positive antibody responses to Ct in the entire population decreased from 82.1% pre-MDA to 35.8% post-MDA, whereas those among ≤ 9-year-olds decreased from 59.6% to 4.1%. These data show that the postintervention decrease in TF was reflected in a drop in anti-Ct antibody responses, suggesting that antibody responses could be useful indicators for post-validation surveillance.

To evaluate visual acuity outcome from cataract surgery based on a population-based survey among people aged 50 years and older in Lumbini Zone and Chitwan District of Nepal.A randomly selected, population-based cross sectional epidemiological study of blindness, visual impairment and cataract surgical outcome was conducted. All subjects underwent a comprehensive ocular examination by an ophthalmic assistant, while people with visual impairment (visual acuity less than 6/18) after refraction and all cataract surgical cases underwent dilated fundus examination by an ophthalmologist.5,916 people were enumerated and 5,141 (86.9%) examined. Among the 359 people who had cataract surgery, 485 eyes were included in the study. First eye surgery was before 2000 in 84 (23%), between 2000 and 2003 in 130 (36%), and after 2003 in 145 (41%). A presenting visual acuity ≥ 6/18 was achieved in 298 (61.4%) eyes (10 [17.8%] and 288 [67.1%] of aphakic and pseudophakic eyes, respectively) and best corrected vision ≥ 6/18 in 411 (84.7%) in all eyes. A presenting visual acuity less than 6/60 was found in 27 (6.3%) pseudophakic eyes. There was no significant difference in visual outcome based on age, sex, literacy, or institution. Uncorrected refractive error was the main cause (72.9%) of visual impairment in pseudophakic eyes.Visual acuity outcome after cataract surgery requires further improvement to meet World Health Organization standards, particularly improvement in preoperative biometry and refractive services. The same quality cataract surgery was provided in and equitably distributed throughout Lumbini Zone and Chitwan District independent of age, sex, literacy or location.

To determine the prevalence of blindness, visual impairment and the cataract surgical coverage for people aged 50 years and older in the Lumbini Zone and the Chitwan District (Narayani Zone) of Nepal.A population-based cross-sectional study in 2006 selected subjects aged 50 years and older through a random multistage cluster sampling and door-to-door enumeration. Ophthalmic examination included visual-acuity assessment and refraction, and anterior and posterior segment examination of the eyes carried out by a trained ophthalmologist and two ophthalmic assistants at centralised locations.The survey examined 5138 of 5196 persons enumerated (response rate of 86.8%). The mean age of the subjects was 61 (SD 9.2) years, and 2701 (52.6%) subjects were women. The age-sex-adjusted prevalence of blindness (best presenting vision6/60) and visual impairment (better-eye presenting visual acuity of6/18 toor = 6/60) were 4.6% (95% CI 3.4 to 5.8) and 18.9% (95% CI 16.4 to 21.4), respectively. Blindness was significantly lower in the hill (3.3%) compared with the plain (5.8%) regions (OR 0.6; 95% CI 0.4 to 0.9). The primary causes for blind eyes were cataract (n = 228, 48.1%), refractive error (n = 149, 31.4%), retinal disorders (n = 19, 4.0%) and corneal opacity (n = 18, 3.8%). The overall cataract surgical coverage was 66.6%. Cataract surgical coverage was not significantly associated with age, sex, literacy or District.Although the prevalence of blindness and visual impairment is lower than 10 years ago, particularly among women, correctable blindness due to cataract and refractive error (79.5% of blind people) remains a significant population health problem in Lumbini Zone and Chitwan District.

Background: Recently, a significant association between Chlamydia trachomatis infection and postoperative trachomatous trichiasis (TT) recurrence was shown. The current study evaluated whether azithromycin treatment at the time of surgery could reduce recurrence. Methods: As part of Nepal’s national trachoma control programme, patients received azithromycin (53 patients) or placebo (56 patients) at surgery. Conjunctivae were graded for trachoma and swabbed to detect chlamydiae preoperatively and postoperatively up to 12 months. Logistic regression was performed for associations of treatment option with recurrence, infection, and active trachoma (by eye and by patient). Results: TT recurrence was 28.9% at 12 months. Recurrence was significantly lower for those with major TT at baseline in the azithromycin group at 12 months (p = 0.03); incident recurrence was also significantly lower at 6 months (OR, 0.056; 95% CI, 0 to 0.423; p = 0.004). There was a trend for increased recurrence among those with minor TT at baseline and for reduction of active trachoma and infection in the azithromycin group but not the placebo group. Conclusion: These data suggest that azithromycin treatment at the time of surgery may be warranted for patients with major TT. However, treatment should be investigated further for minor TT, for efficacy at subsequent time intervals and in other trachoma endemic settings.

High-quality, comprehensive pediatric cataract surgery programs have recently developed in low-income countries, but postoperative care has lagged. This study evaluated the post-cataract surgery follow-up program implemented in March 2011 at the Lumbini Eye Institute in Bhairahawa, Nepal, which included a full-time pediatric counselor and program director, a specific database, a tracking system, and cell phone reminders.Baseline data for all cataract surgical patients16 years of age were obtained retrospectively from hospital administrative records for 2009, the year prior to program introduction, and prospectively for all cases between March 1, 2011, and February 28, 2012. The statistical significance of the difference in the proportion of children attending follow-up in 2009 versus 2011-12 was calculated, and the overall program costs for 2011-12 was determined based on hospital records.In 2011-12, 334 children (248 males [74%]) underwent cataract surgery, including 89 Nepali (27%) and 245 Indian (73%) children. The proportion of boys was significantly higher in 2011-12 compared to 2009, but there were no differences in terms of age or distance to hospital. In 2009, 87%, 60%, and 37% attended their first, second, and third follow-up visits, respectively. Follow-up rates improved significantly to 96%, 81%, and 57%, respectively, after the implementation of the postoperative follow-up program. The 2011-12 program is estimated to have cost US$17,444.The new post-cataract surgery program resulted in improved follow-up at relatively little additional cost.

Background Bharatpur Eye Hospital in Chitwan District, a primarily agrarian setting in south-central Nepal, reduced the number of diagnostic screening and treatment (DST) camps by one half (151 to 75) in an attempt to increase both the efficiency of its outreach program and the number of people that go directly to the hospital for service. The Hospital evaluated the two program models in terms of program costs, cataract surgical utilization, hospital direct payment and patient equity. Methods The study is a prospective, before and after, study of the impact of an alternate outreach model on cataract service utilization patterns and cost per outreach camp and cost per cataract surgery at Bharatpur Eye Hospital, comparing the service years July 2006 to June 2007, with July 2007 to June 2008. Study findings were based on routinely gathered hospital and outreach administrative data. Results The total cost of the DST camps decreased by approximately US$2000. The cost per camp increased from US$52 to $78 and the cost per cataract surgery decreased from US$ 3.80 to $3.20. The number of patients who went directly to the hospital, and paid for cataract surgery, increased from 432 (17%) to 623 (25%). The total number of cataract surgical procedures at Bharatpur Eye Hospital remained very similar between the two service years (2501 and 2449, respectively). The presenting visual acuity and sex of the two cataract surgical populations were very similar (favouring women, 53 and 55% in the two years, respectively). A shift toward younger men and women occurred with a 245 (64%) increase in people age 50-59 years, and shift away from people age 70 years and older with a 236 (22%) reduction. The age and sex distribution of the direct paying patients were very similar in the two years. Conclusion The new, more concentrated, more rural DST model of service delivery reduced overall outreach program costs, cost per cataract surgery transported, while increasing direct payments to the hospital, with a significant decrease in the number of people age 70 and older in the first year.

Background Trachoma is the leading preventable cause of global blindness. A balanced Th1/Th2/Th3 immune response is critical for resolving Chlamydia trachomatis infection, the primary cause of trachoma. Despite control programs that include mass antibiotic treatment, reinfection and recurrence of trachoma are common after treatment cessation. Furthermore, a subset of infected individuals develop inflammation and are at greater risk for developing the severe sequela of trachoma known as trachomatous trichiasis (TT). While there are a number of environmental and behavioral risk factors for trachoma, genetic factors that influence inflammation and TT risk remain ill defined. Methodology/Findings We identified single nucleotide polymorphisms (SNP) in 36 candidate inflammatory genes and interactions among these SNPs that likely play a role in the overall risk for TT. We conducted a case control study of 538 individuals of Tharu ethnicity residing in an endemic region of Nepal. Trachoma was graded according to World Health Organization guidelines. A linear array was used to genotype 51 biallelic SNPs in the 36 genes. Analyses were performed using logic regression modeling, which controls for multiple comparisons. We present, to our knowledge, the first significant association of TNFA (-308GA), LTA (252A), VCAM1 (-1594TC), and IL9 (T113M) polymorphisms, synergistic SNPs and risk of TT. TT risk decreased 5 times [odds ratio = 0.2 (95% confidence interval 0.11.–0.33), p = 0.001] with the combination of TNFA (-308A), LTA (252A), VCAM1 (-1594C), SCYA 11 (23T) minor allele, and the combination of TNFA (-308A), IL9 (113M), IL1B (5′UTR-T), and VCAM1 (-1594C). However, TT risk increased 13.5 times [odds ratio = 13.5 (95% confidence interval 3.3–22), p = 0.001] with the combination of TNFA (-308G), VDR (intron G), IL4R (50V), and ICAM1 (56M) minor allele. Conclusions Evaluating genetic risk factors for trachoma will advance our understanding of disease pathogenesis, and should be considered in the context of designing global control programs.

PURPOSE Chlamydia trachomatis (Ct) remains the leading global cause of preventable blindness. There are limited data on humoral immune responses in trachoma. Evaluating these responses is important for understanding host-pathogen interactions and informing vaccine design. Antibodies to chlamydial heat shock protein 60 (cHSP60) have been associated with infertility and trachomatous scarring. Other proteins, including chlamydial protease-associated factor (CPAF) and a hypothetical protein unique to the family Chlamydiaceae, CT795, elicit strong immune responses in urogenital infections, but their role in trachomatous disease is unknown. METHODS This study was conducted to expand on previous cHSP60 findings and evaluate the association of CPAF and CT795 antibodies with ocular Ct infection and disease. Clinical trachoma grading was performed, and conjunctival samples were obtained from individuals with trachomatous trichiasis (TT; one or more inturned eyelashes) or inflammatory trachoma without trichiasis and control subjects without disease, all of whom resided in trachoma-endemic regions of Nepal. Ct infection was determined using commercial PCR. IgG and IgA tear antibodies against cHSP60, CT795, and CPAF fusion proteins were measured by quantitative ELISA. RESULTS Significantly higher IgG antibody levels were found against cHSP60, CPAF, and CT795 in the inflammatory cases compared with levels in the controls (P < 0.005 for all three). Ct infection was independently associated with IgG antibodies against all three immunogens in the inflammatory cases but not in the controls (P = 0.025, P = 0.03 and P = 0.017, respectively). Only IgG antibodies against CPAF were significantly elevated among the TT cases (P = 0.013). CONCLUSIONS Among individuals with trachoma, IgG antibody responses to CPAF are likely to be both a marker and risk factor for inflammatory trachoma and severe trachomatous disease.

Background 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). Conclusions 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 Background. 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 http://dx.doi.org/10.1371/journal.pmed.0050014. 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

Trachoma is the leading worldwide cause of preventable blindness. Surgery can alleviate trachomatous trichiasis (TT), the blinding sequelae of trachoma, but recurrence rates are high.To investigate risk factors for TT recurrence.We conducted a prospective case-control cohort study in Nepal that included patients with TT who were undergoing bilamellar tarsal-rotation surgery and control subjects who have scarring but no TT. Conjunctivae were graded for trachoma and swabbed to detect Chlamydia trachomatis by in-house and commercial (Roche Amplicor; Roche Diagnostics Corp, Indianapolis, Ind)-polymerase chain reaction. Univariate and multivariate analyses were performed for associations with chlamydiae and other risk factors.Postoperative TT recurrence rates were 11.1% (4 cases) at 6 months and 25.0% (11 cases) at 12 months while no controls developed TT. Significantly, 5 (45.5%) of 11 patients with TT recurrences at 12 months had chlamydial infection at baseline (odds ratio, 6.0; 95% confidence interval, 1.5-24.3; P =.01), 8 (72.7%) at 6 months (odds ratio, 28; 95% confidence interval, 4.3-181.0; P.001), and 9 (81.8%) at 12 months (odds ratio, 48; 95% confidence interval, 7.5-302.6; P =.00). No controls were infected during this time. Active trachoma and the baseline number of eyelashes touching the globe were also risk factors for TT recurrence.The outcome variable was TT recurrence at 6 and 12 months.To our knowledge, this is the first study to demonstrate that chlamydial infection at the time of surgery and at follow-up is a significant risk factor for postoperative TT recurrence.