The population-based prevalence of trachomatous scarring in a trachoma hyperendemic setting: results from 152 impact surveys in Amhara, Ethiopia.

BACKGROUND: Trachomatous scarring (TS) results from repeated infection with the bacterium Chlamydia trachomatis. Pronounced scarring is an underlying cause of trachomatous trichiasis (TT) that can lead to blindness. Since the condition is irreversible, TS in adults has been considered a marker of past exposure to trachoma infection. The aim of this report was to estimate the population-based prevalence of TS within Amhara, Ethiopia, a region with a historically high burden of trachoma. METHODS: District-level multi-stage cluster surveys were conducted in all districts between 2010 and 2015 to monitor the impact of approximately 5 years of trachoma interventions. Approximately 40 households were sampled per cluster and all participants ages ≥ 1 year were graded for the 5 World Health Organization simplified signs. Before each survey round, trachoma graders participated in a 7-day training and reliability exam that included cases of TS. TS prevalence estimates were weighted to account for sampling design and adjusted for age and sex using post-stratification weighting. RESULTS: Across the 152 districts in Amhara, 208,510 individuals ages 1 year and older were examined for the signs of trachoma. Region-wide, the prevalence of TS was 8.2 %, (95 % Confidence Interval [CI]: 7.7-8.6 %), and the prevalence among individuals ages 15 years and older (n = 110,137) was 12.6 % (95 % CI: 12.0-13.3 %). District-level TS prevalence among individuals ages 15 years and older ranged from 0.9 to 36.9 % and was moderately correlated with district prevalence of TT (r = 0.31; P < 0.001). The prevalence of TS increased with age, reaching 22.4 % among those ages 56 to 60 years and 24.2 % among those ages 61 to 65 years. Among children ages 1 to 15 years TS prevalence was 2.2 % (95 % CI: 1.8-2.8 %), increased with age (P < 0.001), and 5 % of individuals with TS also had trachomatous inflammation-intense (TI). CONCLUSIONS: These results suggest that Amhara has had a long history of trachoma exposure and that a large population remains at risk for developing TT. It is promising, however, that children, many born after interventions began, have low levels of TS compared to other known trachoma-hyperendemic areas.

Milestones in the fight to eliminate trachoma.

PURPOSE: Trachoma, a chronic conjunctivitis that can result in vision loss from trichiasis, is targeted for global elimination by 2020. Several milestones in the long process towards elimination are noteworthy for the impact they have had on changing or accelerating progress. The purpose of this review is to describe the milestones and the impact they have had both for trachoma elimination and beyond. FINDINGS: Eight milestones are presented. They are discovery of the causative agent; development of a clinical grading scheme; establishment of the World Health Organization Alliance for the Global Elimination of Trachoma by 2020; setting targets that define elimination; building an evidence base for trichiasis surgery; azithromycin donation programme; use of the SAFE strategy (Surgery, Antibiotics, Facial cleanliness, and Environmental improvement); and The Global Trachoma Mapping Project. SUMMARY: These milestones have significantly pushed the progress towards elimination. Despite challenges to achieving the goal of elimination by 2020, there is continued commitment into the future to ensure that this preventable cause of blindness is no longer a threat.

Short-term increase in prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus following mass drug administration with azithromycin for trachoma control.

BACKGROUND: Mass drug administration (MDA) with azithromycin is a corner-stone of trachoma control however it may drive the emergence of antimicrobial resistance. In a cluster-randomized trial (Clinical trial gov NCT00792922), we compared the reduction in the prevalence of active trachoma in communities that received three annual rounds of MDA to that in communities that received a single treatment round. We used the framework of this trial to carry out an opportunistic study to investigate if the increased rounds of treatment resulted in increased prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus. Three cross-sectional surveys were conducted in two villages receiving three annual rounds of MDA (3 × treatment arm). Surveys were conducted immediately before the third round of MDA (CSS-1) and at one (CSS-2) and six (CSS-3) months after MDA. The final survey also included six villages that had received only one round of MDA 30 months previously (1 × treatment arm). RESULTS: In the 3 × treatment arm, a short-term increase in prevalence of S. aureus carriage was seen following MDA from 24.6% at CSS-1 to 38.6% at CSS-2 (p < 0.001). Prevalence fell to 8.8% at CSS-3 (p < 0.001). A transient increase was also seen in prevalence of carriage of azithromycin resistant (AzmR) strains from 8.9% at CSS-1 to 34.1% (p < 0.001) in CSS-2 and down to 7.3% (p = 0.417) in CSS-3. A similar trend was observed for prevalence of carriage of macrolide-inducible-clindamycin resistant (iMLSB) strains. In CSS-3, prevalence of carriage of resistant strains was higher in the 3 × treatment arm than in the 1 × treatment (AzmR 7.3% vs. 1.6%, p = 0.010; iMLSB 5.8% vs. 0.8%, p < 0.001). Macrolide resistance was attributed to the presence of msr and erm genes. CONCLUSIONS: Three annual rounds of MDA with azithromycin were associated with a short-term increase in both the prevalence of nasopharyngeal carriage of S. aureus and prevalence of carriage of AzmR and iMLSB S. aureus. TRIAL REGISTRATION: This study was ancillary to the Partnership for the Rapid Elimination of Trachoma, ClinicalTrials.gov NCT00792922 , registration date November 17, 2008.

Evaluation of planned bicanalicular nasolacrimal tube retention in treating punctal stenosis or occlusion secondary to trachoma.

This article evaluates retaining bicanalicular silicone nasolacrimal tube in patients susceptible to restenosis after punctoplasty. Sixty-nine eyes (38 patients) suffering from epiphora due to stenosis or occlusion of both punctae were included in this prospective study. All had 3 snip punctoplasty and bicanalicular silicone nasolacrimal duct insertion. Cases associated with proximal canalicular stenosis or obstructions were excluded. Tolerance to tube presence until the time of loss or removal was evaluated using a score (0 to 2). Average age was 49.71 ± 11.09 years. Tachomatous lesions were detected in all cases of punctal stenosis (48 eyes/69.57%) and membranous occlusion (21 eyes/30.43%). Common canalicular obstruction was additionally found in 12 eyes (17.39%). Absolute improvement was detected in 85% of cases and mean time for tube retention was (29.6 ± 10.2 months) with no difference in presence of common canalicular obstruction (P value: 0.138). Isolated punctal affection favoured tube retention that was well tolerated throughout the follow-up period (P value <0.001). Silicone bicanalicular nasolacrimal tube is an available option for treating acquired punctal stenosis. It is tolerated especially in cases suffering from isolated punctal stenosis. Tube retention could be of value in patients who are at risk of re-occlusion following tube removal.

[Comparison of visual impairment caused by trachoma in China between 1978 and 2006].

OBJECTIVE: To understand the distribution of visual impairment caused by trachoma in China and provide evidences for evaluation of eliminating blinding trachoma in China in the mission of Vision 2020. METHODS: Sampling study. The results from the first year 1987 and second (year 2006) national sampling surveys of disabled persons were analyzed. Chi-square test was performed using SAS 9.30 to analyze the rates of visual impairment caused by trachoma in different groups. Unifactor and multifactor analyses were applied to analyze the relevance between visual impairment caused by trachoma and risk factors, including gender and age. RESULTS: The rate of visual impairment caused by trachoma was 102.01 persons/100 000 in 1987 and 17.62 persons/100 000 in 2006. The percentage of trachoma in all kinds of visual impairment was 14.25% in 1987 and 1.87% in 2006, and the difference was significant (F = 1 382.6, P < 0.01). Spatial aggregation was obvious in visual impairment caused by trachoma. H-aggregation areas included Hubei, Sichuan, Anhui, Shannxi, Guizhou, Hunan provinces and Chongqing Municipality. Survival time without trachoma between 1987 and 2006 was significantly different (F = 2 745.9, P < 0.01). The rate and risk of visual impairment caused by trachoma increased with age. Except the group of > 85 years, the rate of visual impairment caused by trachoma in all age groups in 1987 was significantly higher than that in 2006. The risk of visual impairment caused by trachoma in 1987 was 5.8 times that in 2006. If the other risk factors were not involved, the risk in 1987 was 8.75 times that in 2006. The risk in females was twice that in males. CONCLUSION: Both, the rate and risk of visual impairment caused by trachoma were significantly reduced in China. Impressive progresses were achieved in trachoma prevention and control.

Comparison of trichiasis recurrence after primary bilamellar tarsal rotation or anterior lamellar repositioning surgery performed for trachoma.

BACKGROUND: To compare the trichiasis recurrence rate following bilamellar tarsal rotation or anterior lamellar repositioning, performed as primary surgery for trachomatous trichiasis. DESIGN: Retrospective consecutive case series. PARTICIPANTS: All cases of trachomatous trichiasis undergoing primary surgical correction at Alice Springs Hospital, Alice Springs, Northern Territory, Australia, between 1 June 2001 and 11 June 2011 were included. METHODS: Retrospective chart review. Key baseline, operative and outcome details were collected from the notes. MAIN OUTCOME MEASURE: Recurrent trichiasis was defined as one or more lashes touching the cornea, resulting in recurrent symptoms of trichiasis and warranting further surgery in the opinion of the treating ophthalmologist. RESULTS: Sixty-seven BTR and eighteen ALR procedures were performed, with BTR being performed from 2001 to 2008, and ALR from 2008 to 2011. The mean follow-up times were significantly different for the BTR group (1654 days) and for the ALR group (673 days)(P < 0.001). Kaplan-Meier survival analysis did not reveal any significant differences in recurrence rate between the two procedures overall (P = 0.935). Analysis of the 2008 calendar year (the only year where both procedures were performed and therefore had equal follow-up times) suggested that ALR might have a lower recurrence rate (1/10 ALR recurrences vs. 4/6 BTR recurrences, P = 0.181). CONCLUSIONS: The results do not demonstrate a difference in the recurrence rate between the two techniques. Inconsistent follow times however leave uncertainty in this result, and a larger prospective randomised study is warranted to address this question.

The prevention and management of postoperative trachomatous trichiasis: A systematic review.

Among ocular infections, trachoma is the main cause of blindness. Repeated conjunctival Chlamydia trachomatis infections lead to trichiasis, corneal opacification, and visual impairment. Surgery is often needed to relieve discomfort and preserve vision; however, a high postoperative trachomatous trichiasis (PTT) rate has been observed in various settings. We wanted to know why, whether PTT rates could be reduced, and how to manage the PTT that occurs. We performed a search of the literature. Of 217 papers screened, 59 studies were identified for inclusion as potentially relevant, the majority having been excluded for not directly concerning PTT in humans. Preventing PTT is a major challenge. Only one published trial, the STAR trial in Ethiopia, has reported a cumulative PTT rate <10% one year after surgery. The literature on the management of PTT is sparse. Though no PTT management guidelines are available, high-quality surgery with a low rate of unfavorable outcomes for PTT patients is likely to require enhanced training of a smaller group of highly-skilled surgeons. Based on the surgical complexity and the authors' own experience, the pathway for patients suffering from PTT should be studied further for improvement.

Gender differences in trachomatous scarring prevalence in a formerly trachoma hyperendemic district in Tanzania.

BACKGROUND: Trachoma is a chronic conjunctivitis caused by the bacterium Chlamydia trachomatis. Repeated infections lead to trachomatous conjunctival scarring which can progress to potentially blinding trachomatous trichiasis (TT). In trachoma hyperendemic conditions, women compared to men have an increased risk of scarring and TT, which can progress to blinding corneal opacification. This study determined if there were gender differences in scarring prevalence and severity when trachoma prevalence approaches elimination, in a formerly trachoma hyperendemic region. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional prevalence study was conducted amongst adults age 15 years and older in Kongwa district, Tanzania in 2019. 3168 persons over age 15 years agreed to be examined and had at least one eye with a gradable image. Ocular photographs were graded for scarring according to a published four-step severity scale. Overall, about half of all study participants had scarring. However, more females (52.3%) had any scarring compared to males (47.2%), OR = 1.22 (95% CI = 1.05-1.43). For every year increase in age, there was a 6.5% increase in the odds of having more severe scarring (95% CI: 5.8%, 7.2%). Women were more likely than men to have severe scarring, OR 2.36 (95% CI: 1.84-3.02). Residence in a community with TF≥10% was associated with a 1.6-fold increased odds of any scarring. CONCLUSIONS/SIGNIFICANCE: Overall scarring prevalence and more severe scarring prevalence was higher in females compared to males, even adjusting for age and community TF prevalence. The data suggest that processes occur that lead to women preferentially progressing towards more severe scarring compared to men.

Risk of trachoma in a SAFE intervention area.

To determine prevalence and risk factors of trachoma in communities receiving intervention with the SAFE strategy (surgery, antibiotic, face washing, environmental hygiene), a cross-sectional trachoma survey was undertaken in 2006 in the Enemor district of southern Ethiopia where the SAFE program has been implemented for over five years. A sample of 374 household heads and 2,080 individuals were interviewed and examined for trachoma using an established trachoma grading system of the World Health Organization. The most prominent risk factors were identified with logistic regression analysis. Among individuals >14 years of age, the prevalence of trichiasis was 9.04 % [confidence interval (CI) 7.4-10.6]. People >40 years of age [odds ratio (OR) 1.7; CI 1.2-2.7), women (OR 2.2; CI 1.1-4.3), and illiterates (OR 3; CI 1.4-6.8) had increased risk of trichiasis. Coverage of surgical and antibiotic services was 46 and 85.5 %, respectively. Prevalence of active follicular trachoma (TF) in children aged 1-9 years was 33.1 % (CI 29.4-37.1). Unclean faces (OR 5.9; CI 4.3-8.3) and not being in school (OR 2.1; CI 1.3-3.3) were significantly associated with TF. Clean faces were observed in 56.1 % of children and improved with age and schooling (P < 0.001, Chi-squared test). Household latrine use (74.4 %) was associated with knowledge about SAFE and economic level (P ≤ 0.004, Chi-squared tests). Elderly illiterate women remain at risk of becoming blind from trachoma even in intervention areas. Trachoma particularly affects children without clean faces or opportunity for schooling. Provision of SAFE services with high coverage should be sustained in trachoma-hyperendemic areas.

Improving data use in trachomatous trichiasis programmes: operationalisation of the TT Tracker.

Trachoma is a disease of the eye and the leading infectious cause of blindness worldwide. Years of repeated infections can cause in-turning of the lashes so that they rub against the eyeball, causing pain, discomfort and, if left untreated, blindness. This is known as trachomatous trichiasis (TT) and can be remedied by surgery. To improve oversight and reporting of TT outreach, Sightsavers developed a mobile phone application called the TT Tracker so that TT surgeons, assistants and supervisors can collect and analyse information about surgical outcomes and performance and determine when and where follow-up appointments are required. The TT Tracker is being used by seven national programmes. Examples of use and programme improvements from Nigeria, Benin and Senegal are discussed here.

Trachoma, the world's leading infectious cause of blindness: The remaining gap in care and access to basic handwashing facilities.

PURPOSE: Trachoma, the world's leading infectious cause of blindness, has been targeted by the WHO for elimination through the SAFE strategy: surgery, antibiotics, facial cleanliness, and environmental improvement. Although significant progress has been made, there remains a gap in care. This project studied the association of geographical distribution of the remaining need for trachoma intervention and its association with access to basic handwashing facilities at home, as an indicator of water/sanitation infrastructure. We hypothesized that poor water sanitation would correspond to areas where trachoma intervention is still required. DESIGN: Retrospective analysis using the WHO Global Health Observatory. Spatial, correlation, and simple and multivariable regression analyses were used. METHODS: Using data from the WHO Global Health Observatory, a total of 194 countries were analyzed. Two choropleth maps were created, with inset maps focused on the South Pacific region, where the top 5 countries with the greatest population proportion requiring trachoma intervention are located. RESULTS: Correlations and the simple regression model of total population with access to handwashing facilities as the only risk factor were insignificant. However, the multivariable regression models with access to handwashing facilities (total, urban, and rural) and population density as risk factors for trachoma intervention were significant. CONCLUSION: Poor water/sanitation infrastructure correlates with trachoma burden. Therefore, water/sanitation infrastructure improvement is a worthwhile target in the efforts toward trachoma elimination, but further research on the association between these important public health indicators is warranted.

Innate immune responses and modified extracellular matrix regulation characterize bacterial infection and cellular/connective tissue changes in scarring trachoma.

Trachoma is the most common infectious cause of blindness and a major public health problem in many developing countries. It is caused by recurrent ocular infection with Chlamydia trachomatis in childhood, with conjunctival scarring seen later in life. The pathogenesis of trachomatous scarring, however, is poorly understood, and this study was carried out to investigate the immunofibrogenic correlates of trachomatous conjunctival scarring. A case-control study of 363 cases with conjunctival scarring and 363 control participants was conducted. Investigations included in vivo confocal microscopy (IVCM) assessment, quantitative real-time PCR gene expression, C. trachomatis detection, and nonchlamydial bacterial culture. Trachomatous scarring was found to be strongly associated with a proinflammatory, innate immune response with increased expression of psoriasin, interleukin-1ß, tumor necrosis factor alpha, defensin-ß4A, chemokine ligand 5, and serum amyloid A1. There was also differential expression of various modifiers of the extracellular matrix, including metalloproteinases 7, 9, 10, and 12, tissue inhibitor of matrix metalloproteinase 1, and secreted protein acidic cystein-rich-like 1. The expression of many of these genes was also significantly associated with the presence of nonchlamydial bacterial infection. These infections had a marked effect on conjunctival immune processes, including an increased inflammatory infiltrate and edema seen with IVCM. This study supports the possibility that the immunofibrogenic response in scarring trachoma is partly stimulated by nonchlamydial bacterial infection, which is characterized by the expression of innate factors.

Long-term results of tarsal margin rotation and extended posterior lamellae advancement for end stage trachoma.

PURPOSE: To report the long-term results of tarsal margin rotation with extended posterior lamellae advancement in the management of cicatricial entropion, trichiasis, and accompanying misdirected metaplastic lashes of the upper eyelid due to trachoma. METHODS: Tarsal margin rotation and extended advancement of posterior lamellae were performed in 27 eyelids of 15 consecutive patients for correction of cicatricial entropion, metaplastic lashes, and trichiasis. RESULTS: In all eyes, functional success, which was defined as normal mucocutaneous junction position and repositioning the lashes away from the ocular surface, were achieved. No recurrence was detected over a mean follow-up of 40.04 ± 16.61 (range, 18-72) months. Pyogenic granuloma, which was treated with complete excision, developed at the cut end of the tarsal conjunctiva in 3 cases. Cosmetic results were satisfactory in terms of both patients and examiner. CONCLUSION: Tarsal margin rotation with extended posterior lamellae advancement appears to be effective with no recurrence in managing cicatricial entropion and accompanying multiple eyelash problems of the upper eyelid due to trachoma.

Anterior lamellar marginal z-plasty with transverse tarsotomy for management of trichiasis with cicatricial entropion--a new surgical approach.

BACKGROUND: Trichiasis is the main risk factor for corneal opacification. The primary treatment of trichiasis is surgical. Successful surgery is likely to halt the progression of corneal opacity. The aim of the study is to report the efficacy of the anterior lamellar marginal z-plasty combined with transverse tarsotomy in the management of severe trichiasis andcicatricial entropion of upper eyelid. METHODS: A prospective study was carried out from January 2009 to June 2012, on 54 eyelids (44 patients) who underwent anterior lamellar marginal z-plasty with transverse tarsotomy for correction of trichiasis and cicatricial entropion involving upper eyelid with a minimum of 6 months' follow-up. Results were classified according to the presence and location of residual trichiasis and symptoms were assessed according to a three-level subjective scale (better, worse or no change). Failure was defined as recurrent trichiasis with one or more lashes touching any part of cornea in primary position. Secondary outcomes were visual acuity and corneal opacification. RESULTS: At the end of six month period, none of patients had any trichiatic eye lash touching the cornea in primary position (100% success). Forty-eight (88.9%) of the operated eyelids were free of trichiasis, while residual trichiasis was noticed only in 6 (11.1%) operated lids. At the end of six months, there was a significant reduction of lash burden from median of 12 trichiatic lashes from the base line to the median of 2. All the patients reported significant reduction in symptoms of irritation. Significant improvement in visual acuity (p < 0.000) and reduction in the density of corneal opacity (p < 0.000) was notified from the base line. CONCLUSION: Anterior lamellar marginal z-plasty combined with transverse tarsotomy seems to have promising surgical outcome for the correction oftrichiasis and cicatricial entropion secondary to cicatricial trachoma.

Atypical Corneal Phenotype in Patients With Trachoma and Secondary Amyloidosis.

PURPOSE: To report clinical presentation, in vivo confocal microscopic features, and corneal phenotype in patients with trachomatous keratopathy (TK) and secondary amyloidosis. METHODS: Histopathological records of all patients undergoing keratoplasty at the Dr. Rajendra Prasad Centre for Ophthalmic Sciences over a 3-year period were scanned retrospectively for a diagnosis of TK and amyloidosis. Demographic profile and details of preoperative comprehensive ophthalmic assessment were extracted. The histopathology was freshly reviewed. RESULTS: Fifteen patients (29 eyes) with TK and atypical corneal involvement due to amyloid deposition were identified. Herbert's pits and upper palpebral conjunctival scarring were present in all cases. Central or total diffuse corneal scarring was present involving the anterior stroma in 5 (31%) and the full thickness of the cornea in 11 (69%) of the eyes. Eight (73%) of 11 patients with deep stromal amyloid deposits revealed bilateral, discrete, blue-white opacities at the level of deep stroma and Descemet membrane (DM). Endothelial cells were atrophic and flattened with gutta formation. Confoscans revealed hyperreflective, needle-shaped crystalline deposits of extracellular amyloid at various depths of the corneal stroma up to DM. All host corneal buttons demonstrated Congo red-positive amyloid deposits on histopathological examination. CONCLUSIONS: We describe a distinct form of TK unlike the usual presentation of dense, leucomatous, vascularized corneal scarring in trachoma. We believe that amyloid deposits in DM and the corneal endothelium have not previously been reported in patients with trachoma.

Trachoma.

Trachoma is a neglected tropical disease caused by infection with conjunctival strains of Chlamydia trachomatis. It can result in blindness. Pathophysiologically, trachoma is a disease complex composed of two linked chronic processes: a recurrent, generally subclinical infectious-inflammatory disease that mostly affects children, and a non-communicable, cicatricial and, owing to trichiasis, eventually blinding disease that supervenes in some individuals later in life. At least 150 infection episodes over an individual's lifetime are needed to precipitate trichiasis; thus, opportunity exists for a just global health system to intervene to prevent trachomatous blindness. Trachoma is found at highest prevalence in the poorest communities of low-income countries, particularly in sub-Saharan Africa; in June 2021, 1.8 million people worldwide were going blind from the disease. Blindness attributable to trachoma can appear in communities many years after conjunctival C. trachomatis transmission has waned or ceased; therefore, the two linked disease processes require distinct clinical and public health responses. Surgery is offered to individuals with trichiasis and antibiotic mass drug administration and interventions to stimulate facial cleanliness and environmental improvement are designed to reduce infection prevalence and transmission. Together, these interventions comprise the SAFE strategy, which is achieving considerable success. Although much work remains, a continuing public health problem from trachoma in the year 2030 will be difficult for the world to excuse.

Conjunctival transcriptome in scarring trachoma.

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 (IL1ß, 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 T(H)1 response (INDO and NOS2A) and no association between a T(H)2 response and cases. The epithelium appears to be actively involved in late cicatricial stages of trachoma through the production of proinflammatory factors (IL1ß, 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.

Remaining questions about clinical variola major.

After the recent summary of World Health Organization-authorized research on smallpox, several clinical issues remain. This policy review addresses whether early hemorrhagic smallpox is disseminated intravascular coagulation and speculates about the cause of the high mortality rate among pregnant women and whether ocular smallpox is partly the result of trachoma or vitamin A deficiency. The joint destruction common in children with smallpox might be prevented by antiviral drugs, but intraarticular infusion of antiviral drugs is unprecedented. Development of highly effective antiviral drugs against smallpox raises the issue of whether postexposure vaccination can be performed without interference by an antiviral drug. Clinicians should consider whether patients with smallpox should be admitted to general hospitals. Although an adequate supply of second-generation smallpox vaccine exists in the United States, its use is unclear. Finally, political and ethical forces suggest that destruction of the remaining stocks of live smallpox virus is now appropriate.