Application of molecular tools in the control of blinding trachoma.

The use of anti-chlamydial antibiotics for trachoma control is based on the assumption that most people with clinically active disease have conjunctival infection with Chlamydia trachomatis. In high prevalence areas, this is generally true. As prevalence decreases, however, the positive predictive value of clinical signs for C. trachomatis infection also decrease. In this paper, the case for using laboratory assays to guide trachoma control strategies is presented, molecular methods for diagnosis (such as a ligase chain reaction and a polymerase chain reaction [PCR]) are compared with earlier techniques, and recent findings of ongoing studies using a quantitative PCR are reviewed. In addition, the contribution of genotyping to our understanding of the epidemiology and biology of C. trachomatis is considered

Antibiotics for trachoma.

BACKGROUND: Trachoma is the world's leading infectious cause of blindness. In 1997 the World Health Organization (WHO) launched an Alliance for the Global Elimination of Trachoma by the year 2020, based on the 'SAFE' strategy (surgery, antibiotics, facial cleanliness and environmental improvement). OBJECTIVES: To assess the evidence supporting the antibiotic arm of the SAFE strategy by assessing the effects of antibiotics on both active trachoma (primary objective) and on Chlamydia trachomatis (C. trachomatis) infection of the conjunctiva (secondary objective). SEARCH STRATEGY: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2010, Issue 11), MEDLINE (January 1950 to December 2010), EMBASE (January 1980 to December 2010), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (December 2010) and ClinicalTrials.gov (www.clinicaltrials.gov) (December 2010). We used the Science Citation Index to look for articles that cited the included studies. We searched the reference lists of identified articles and we contacted authors and experts for details of further relevant studies. There were no language or date restrictions in the search for trials. The electronic databases were last searched on 12 December 2010. SELECTION CRITERIA: We included randomised trials that satisfied either of two criteria: (a) trials in which topical or oral administration of an antibiotic was compared to placebo or no treatment in people or communities with trachoma, (b) trials in which a topical antibiotic was compared with an oral antibiotic in people or communities with trachoma. A subdivision of particular interest was trials in which topical tetracycline or chlortetracycline and oral azithromycin were compared with each other, or in which one of these treatments was compared with placebo or no treatment, as these are the two WHO recommended antibiotics. We considered individually randomised and cluster-randomised trials separately. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted investigators for missing data. Where appropriate, the effect estimates from the individual studies (risk ratios) were pooled using a random-effects model. MAIN RESULTS: A total of 14 trials randomised individuals with trachoma to oral antibiotic, topical antibiotic, both, or control (no treatment or placebo) and were eligible for inclusion in this review (n = 3587). Overall, the quality of the evidence provided from these trials was low. Nine of the trials compared antibiotic treatment to control. Most of the studies found a beneficial effect of treatment on active trachoma and ocular chlamydial infection at three and 12 months follow up. There was considerable clinical and statistical heterogeneity between trials, which meant that it was difficult to reliably estimate the size of the treatment effect. It is likely to be in the region of a 20% relative risk reduction. Seven of the 14 trials compared the effectiveness of oral and topical antibiotics. There was no consistent evidence as to whether oral or topical antibiotics were more effective, although one trial suggested that a single dose of oral azithromycin was significantly more effective than unsupervised use of topical tetracyclineA further eight trials assessed the effectiveness of community-based treatment. In five trials antibiotic treatment was compared to no (or delayed) treatment (57 communities), and in three trials oral antibiotic was compared to topical treatment (12 communities). The quality of the evidence provided by these trials was variable but at least one trial was considered to provide high quality evidence. There was evidence that community-based antibiotic treatment reduced the prevalence of active trachoma and ocular infection 12 months after single-dose treatment. There was some evidence that oral azithromycin was more effective than topical tetracycline as a community treatment. Data on adverse effects were not consistently reported however there were no reported serious adverse events associated with treatment with oral azithromycin or topical tetracycline; in one sample survey of 671 people treated with azithromycin between 10% and 15% experienced gastrointestinal adverse effects (nausea or vomiting, or both). AUTHORS' CONCLUSIONS: Antibiotic treatment reduces the risk of active trachoma and ocular chlamydial infection in people infected with C. trachomatis, but we do not know for certain the size of the treatment effect in individuals. Mass antibiotic treatment with single-dose oral azithromycin reduces the prevalence of active trachoma and ocular infection in communities

Endemic treponemal diseases.

The endemic treponemal diseases, consisting of yaws, bejel (endemic syphilis) and pinta, are non-venereal infections closely related to syphilis, and are recognized by WHO as neglected tropical diseases (NTDs). Despite previous worldwide eradication efforts the prevalence of yaws has rebounded in recent years and the disease is now a major public health problem in 14 countries. Adequate data on the epidemiology of bejel and pinta is lacking. Each disease is restricted to a specific ecological niche but all predominantly affect poor, rural communities. As with venereal syphilis, the clinical manifestations of the endemic treponemal diseases are variable and can be broken down in to early stage and late stage disease. Current diagnostic techniques are unable to distinguish the different causative species but newer molecular techniques are now making this possible. Penicillin has long been considered the mainstay of treatment for the endemic treponemal diseases but the recent discovery that azithromycin is effective in the treatment of yaws has renewed interest in these most neglected of the NTDs, and raised hopes that global eradication may finally be possible

Multilevel Analysis of Trachomatous Trichiasis and Corneal Opacity in Nigeria : The Role of Environmental and Climatic Risk Factors on the Distribution of Disease.

Funding: Jennifer L Smith was supported by the International Trachoma Initiative through a grant from the Bill and Melinda Gates Foundation. Anthony Solomon is a Wellcome Trust Intermediate Clinical Fellow (098521). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Perspectives of National Coordinators and Partners on the Work of the Global Trachoma Mapping Project.

PURPOSE: Neglected tropical diseases (NTDs) affect people living in the poorest regions of the world and their debilitating effects perpetuate the poverty cycle. Understanding the distribution of NTDs is crucial for effective intervention delivery. In 2012, the Global Trachoma Mapping Project (GTMP) was initiated to map >1800 suspected trachoma endemic districts by March 2015. This research was carried out to better understand the implementation experience and identify lessons which might inform the GTMP and similar initiatives. METHODS: Using grounded theory methodology, semi-structured interviews were conducted with key informants from six countries with 63% of the global mapping backlog (Ethiopia, Malawi, Mozambique, Nigeria, Solomon Islands, and Yemen). Interviews were transcribed, coded, and findings separated into categories. RESULTS: Three themes were identified during the research; planning and operations, technical implementation, and governance. The project was felt to be most successful in countries where the Ministry of Health was actively engaged in setting standards, ensuring capacity building for government staff, and guiding the training, data collection, analysis, and interpretation of data. Standardized tools, training platforms, and the use of electronic data capture increased confidence in the reliability of the survey data, informed quality improvement efforts within survey implementation, and the immediate release of results empowered end-user decision-makers. Regional collaboration between endemic countries bolstered program manager competence and confidence, while reinforcing partnerships essential to the success of the GTMP. CONCLUSIONS: We depict how innovative characteristics of the GTMP, and lessons learned from its implementation, can strengthen similar initiatives to map disease prevalence and risk factors

Yaws.

Yaws is a non-venereal endemic treponemal infection caused by Treponema pallidum sub-species pertenue, a spirochaete bacterium closely related to Treponema pallidum ssp. pallidum, the agent of venereal syphilis. Yaws is a chronic, relapsing disease predominantly affecting children living in certain tropical regions. It spreads by skin-to-skin contact and, like syphilis, occurs in distinct clinical stages. It causes lesions of the skin, mucous membranes and bones which, without treatment, can become chronic and destructive. Treponema pallidum ssp. pertenue, like its sexually-transmitted counterpart, is exquisitely sensitive to penicillin. Infection with yaws or syphilis results in reactive treponemal serology and there is no widely available test to distinguish between these infections. Thus, migration of people from yaws-endemic areas to developed countries may present clinicians with diagnostic dilemmas. We review the epidemiology, clinical presentation and treatment of yaws

Yaws.

INTRODUCTION: Yaws, caused by Treponema pallidum ssp. pertenue, is endemic in parts of West Africa, Southeast Asia and the Pacific. The WHO has launched a campaign based on mass treatment with azithromycin, to eradicate yaws by 2020. SOURCES OF DATA: We reviewed published data, surveillance data and data presented at yaws eradication meetings. AREAS OF AGREEMENT: Azithromycin is now the preferred agent for treating yaws. Point-of-care tests have demonstrated their value in yaws. AREAS OF CONTROVERSY: There is limited data from 76 countries, which previously reported yaws. Different doses of azithromycin are used in community mass treatment for yaws and trachoma. GROWING POINTS: Yaws eradication appears an achievable goal. The programme will require considerable support from partners across health and development sectors. AREAS TIMELY FOR DEVELOPING RESEARCH: Studies to complete baseline mapping, integrate diagnostic tests into surveillance and assess the impact of community mass treatment with azithromycin are ongoing

Yaws

Introduction Yaws, caused by Treponema pallidum ssp. pertenue, is endemic in parts of West Africa, Southeast Asia and the Pacific. The WHO has launched a campaign based on mass treatment with azithromycin, to eradicate yaws by 2020. Sources of data We reviewed published data, surveillance data and data presented at yaws eradication meetings. Areas of agreement Azithromycin is now the preferred agent for treating yaws. Point-of-care tests have demonstrated their value in yaws. Areas of controversy There is limited data from 76 countries, which previously reported yaws. Different doses of azithromycin are used in community mass treatment for yaws and trachoma. Growing points Yaws eradication appears an achievable goal. The programme will require considerable support from partners across health and development sectors. Areas timely for developing research Studies to complete baseline mapping, integrate diagnostic tests into surveillance and assess the impact of community mass treatment with azithromycin are ongoin

Comparing the performance of cluster random sampling and integrated threshold mapping for targeting trachoma control, using computer simulation.

BACKGROUND: Implementation of trachoma control strategies requires reliable district-level estimates of trachomatous inflammation-follicular (TF), generally collected using the recommended gold-standard cluster randomized surveys (CRS). Integrated Threshold Mapping (ITM) has been proposed as an integrated and cost-effective means of rapidly surveying trachoma in order to classify districts according to treatment thresholds. ITM differs from CRS in a number of important ways, including the use of a school-based sampling platform for children aged 1-9 and a different age distribution of participants. This study uses computerised sampling simulations to compare the performance of these survey designs and evaluate the impact of varying key parameters. METHODOLOGY/PRINCIPAL FINDINGS: Realistic pseudo gold standard data for 100 districts were generated that maintained the relative risk of disease between important sub-groups and incorporated empirical estimates of disease clustering at the household, village and district level. To simulate the different sampling approaches, 20 clusters were selected from each district, with individuals sampled according to the protocol for ITM and CRS. Results showed that ITM generally under-estimated the true prevalence of TF over a range of epidemiological settings and introduced more district misclassification according to treatment thresholds than did CRS. However, the extent of underestimation and resulting misclassification was found to be dependent on three main factors: (i) the district prevalence of TF; (ii) the relative risk of TF between enrolled and non-enrolled children within clusters; and (iii) the enrollment rate in schools. CONCLUSIONS/SIGNIFICANCE: Although in some contexts the two methodologies may be equivalent, ITM can introduce a bias-dependent shift as prevalence of TF increases, resulting in a greater risk of misclassification around treatment thresholds. In addition to strengthening the evidence base around choice of trachoma survey methodologies, this study illustrates the use of a simulated approach in addressing operational research questions for trachoma but also other NTDs