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Background: Trachoma causes blindness due to repeated conjunctival infection by Chlamydia trachomatis (Ct). Transmission intensity is estimated, for programmatic decision-making, by prevalence of the clinical sign trachomatous inflammation-follicular (TF) in children aged 1-9 years. Research into complementary indicators to field-graded TF includes work on conjunctival photography, tests for ocular Ct infection, and serology. The perceived acceptability and feasibility of these indicators among a variety of stakeholders is unknown., Methodology: Focus group discussions (FGDs) with community members and in-depth interviews (IDIs) with public health practitioners in Tanzania were conducted. FGDs explored themes including participants' experience with, and thoughts about, different diagnostic approaches. The framework method for content analysis was used. IDIs yielded lists of perceived strengths of, and barriers to, implementation for programmatic use of each indicator. These were used to form an online quantitative survey on complementary indicators distributed to global stakeholders via meetings, mailing lists, and social media posts., Results: Sixteen FGDs and 11 IDIs were conducted in October-November 2022. In general, all proposed sample methods were deemed acceptable by community members. Common themes included not wanting undue discomfort and a preference for tests perceived as accurate. Health workers noted the importance of community education for some sample types. The online survey was conducted in April-May 2023 with 98 starting the questionnaire and 81 completing it. Regarding barriers to implementing diagnostics, the highest agreement items related to feasibility, rather than acceptability. No evidence of significant differences was found in responses pertaining to community acceptability based on participant characteristics., Conclusions: All of the indicators included were generally deemed acceptable by all stakeholders in Tanzania, although community education around the benefits and risks of different sample types, as well as addressing issues around feasibility, will be key to successful, sustainable integration of these indicators into trachoma programs., Competing Interests: All authors have declared that no competing interests exist., (Copyright: © 2024 Renneker et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The clinical signs of active trachoma are often present in the absence of ocular Chlamydia trachomatis infection, particularly following mass drug administration. Treatment decisions following impact surveys and in post-control surveillance for communities are currently based on the prevalence of clinical signs, which may result in further unnecessary distribution of mass antibiotic treatment and the increased spread of macrolide resistance alleles in 'off-target' bacterial species. We therefore developed a simple, fast, low cost diagnostic assay (DjinniChip) for diagnosis of ocular C. trachomatis for use by trachoma control programmes., Methods: The study was conducted in the UK, Germany and Tanzania. For clinical testing in Tanzania, specimens from a sample of 350 children between the ages of 7 to 15 years, which were part of a longitudinal cohort that began in February 2012 were selected. Two ocular swabs were taken from the right eye. The second swab was collected dry, kept cool in the field and archived at - 80 °C before sample lysis for DjinniChip detection and parallel nucleic acid purification and detection/quantification by qPCR assay., Results: DjinniChip was able to reliably detect > 10 copies of C. trachomatis per test and correctly identified 7/10 Quality Control for Molecular Diagnostics C. trachomatis panel samples, failing to detect 3 positive samples with genome equivalent amounts ≤ 10 copies. DjinniChip performed well across a range of typical trachoma field conditions and when used by lay personnel using a series of mock samples. In the laboratory in Tanzania, using clinical samples the sensitivity and specificity of DjinniChip for C. trachomatis was 66% (95% CI 51-78) and 94.8 (95% CI 91-97%) with an overall accuracy of 90.1 (95% CI 86.4-93)., Conclusions: DjinniChip performance is extremely promising, particularly its ability to detect low concentrations of C. trachomatis and its usability in field conditions. The DjinniChip requires further development to reduce inhibition and advance toward a closed system. DjinniChip results did not vary between local laboratory results and typical trachoma field settings, illustrating its potential for use in low-resource areas to prevent unnecessary rounds of MDA and to monitor for C. trachomatis recrudescence.

Background: Trachoma is the leading infectious cause of blindness. Repeated or persistent ocular infection with Chlamydia trachomatis in childhood leads to conjunctival scarring, usually in adulthood but often earlier in areas with greater disease burden. There are limited longitudinal data examining change in scarring in children, especially where trachoma rates are low., Methodology/principal Findings: A cohort of children, ages 1-9 years, were randomly selected at baseline from 38 communities in Kongwa, Tanzania and followed for 2 years. Rates of trachomatous inflammation-follicular (TF) were <5% over the survey period. At baseline, 1,496 children were recruited and 1,266 (85%) were followed-up. Photographs were obtained at baseline and follow-up and graded for the presence and severity of scarring using a four-point scale ranging between S1-S4. In children without scarring at baseline, 1.6% (20/1,246) were found to have incident scarring, and incident scarring was more common among girls compared to boys. Among children with scarring at baseline, 21% (4/19) demonstrated progression., Conclusions/significance: In this formerly hyper-endemic district, the incidence of new scarring in children ages 1-9 years is low, although 21% of those who had scarring at baseline progressed in severity over the 2-year follow-up period. These data provide support for the thesis that while incident scarring more closely reflects ongoing exposure, progression may involve factors independent of ongoing transmission of trachoma., Competing Interests: The authors have declared that no competing interests exist.

Background: Trachoma, a conjunctivitis caused by repeated infections with Chlamydia trachomatis, remains a significant cause of blindness worldwide. While mass treatments with azithromycin decreases disease and infection, re-emergence occurs, indicating that elimination may require other sustainable interventions. Environmental changes largely focus on facial hygiene and latrines, but further work to identify other possible transmission targets are needed. We sought to determine, in a cross-sectional survey of households of children with active trachoma, if we could detect the presence of Chlamydia trachomatis on household objects and on family members based on sleeping and caretaking patterns., Methods: In five villages in Kongwa, Tanzania, children

Background: Trachoma is a progressive blinding disease initiated by infection of the conjunctiva with Chlamydia trachomatis. Repeated infections are thought to cause chronic inflammation, which drives scarring, leading to in-turning of the eyelids. The relationship between C. trachomatis, clinical inflammation and scarring development in children is not fully understood due to a paucity of longitudinal studies with infection data at frequent follow-up., Methods and Findings: This longitudinal cohort study took place in northern Tanzania. Children aged 6-10 years at baseline were eligible for inclusion. Participants were visited every three months for four years. Clinical signs and conjunctival swabs for C. trachomatis detection by qPCR were collected at each time-point. Conjunctival photographs from baseline and final time-points were graded and compared side-by-side to determine scarring incidence and progression. Of the 666 children enrolled in the study, outcome data were obtained for 448. Scarring progression was detected in 103/448 (23%) children; 48 (11%) of which had incident scarring and 55 (12%) had progression of existing scarring. Scarring was strongly associated with increasing episodes of trachomatous papillary inflammation (TP). Weaker associations were found between episodes of C. trachomatis infection and follicular trachoma (TF) with scarring progression in unadjusted models, which were absent in multivariable analysis after adjusting for inflammation (multivariable results: C. trachomatis p = 0.44, TF p = 0.25, TP p = <0.0001, age p = 0.13, female sex p = 0.05). Individuals having TP at 30% or more of the time-points they were seen had an odds ratio of 7.5 (95%CI = 2.7-20.8) for scarring progression relative to individuals without any TP detected during the study period., Conclusions: These data suggest that the effect of infection on scarring progression is mediated through papillary inflammation, and that other factors contributing to the development of inflammation, in addition to C. trachomatis infection, may be important in driving conjunctival scarring progression in children. The addition of TP as a measure in trachoma control programs would provide an indication of the future risk of developing scarring sequelae., Competing Interests: The authors have declared that no competing interests exist.

Background: Trachoma, caused by Chlamydia trachomatis, remains the leading infectious cause of blindness worldwide. Persistence and progression of the resulting clinical disease appears to be an immunologically mediated process. Azithromycin, which is distributed at the community level for trachoma control, has immunomodulatory properties. We investigated the impact of one round of oral azithromycin on conjunctival immune responses, C. trachomatis infection and clinical signs three- and six- months post treatment relative to three pre-treatment time-points., Methodology: A cohort of children aged 6 to 10 years were recruited from a trachoma endemic region of northern Tanzania and were visited five times in a 12-month period. They were examined for clinical signs of trachoma and conjunctival swabs were collected for laboratory analysis. C. trachomatis infection was detected and the expression of 46 host genes was quantified using quantitative PCR. All community members were offered azithromycin treatment immediately after the six-month timepoint according to international guidelines., Findings: The prevalence of C. trachomatis infection and inflammatory disease signs were significantly reduced three- and six- months post-mass drug administration (MDA). C. trachomatis infection was strongly associated with clinical signs at all five time-points. A profound anti-inflammatory effect on conjunctival gene expression was observed 3 months post-MDA, however, gene expression had largely returned to pre-treatment levels of variation by 6 months. This effect was less marked, but still observed, after adjusting for C. trachomatis infection and when the analysis was restricted to individuals who were free from both infection and clinical disease at all five time-points. Interestingly, a modest effect was also observed in individuals who did not receive treatment., Conclusion: Conjunctival inflammation is the major clinical risk factor for progressive scarring trachoma, therefore, the reduction in inflammation associated with azithromycin treatment may be beneficial in limiting the development of potentially blinding disease sequelae. Future work should seek to determine whether this effect is mediated directly through inhibition of pro-inflammatory intracellular signalling molecules, through reductions in concurrent, sub-clinical infections, and/or through reduction of infection exposure., Competing Interests: The authors have declared that no competing interests exist.

Background: Trachoma, the leading infectious cause of blindness worldwide, is caused by conjunctival Chlamydia trachomatis infection. Trachoma is diagnosed clinically by observation of conjunctival inflammation and/or scarring; however, there is evidence that monitoring C. trachomatis infection may be required for elimination programmes. There are many commercial and 'in-house' nucleic acid amplification tests for the detection of C. trachomatis DNA, but the majority have not been validated for use with ocular swabs. This study evaluated a commercial assay, the Fast-Track Vaginal swab kit, using conjunctival samples from trachoma-endemic areas. An objective, biostatistical-based method for binary classification of continuous PCR data was developed, to limit potential user-bias in diagnostic settings., Methods: The Fast-Track Vaginal swab assay was run on 210 ocular swab samples from Guinea-Bissau and Tanzania. Fit of individual amplification curves to exponential or sigmoid models, derivative and second derivative of the curves and final fluorescence value were examined for utility in thresholding for determining positivity. The results from the Fast-Track Vaginal swab assay were evaluated against a commercial test (Amplicor CT/NG) and a non-commercial test (in-house droplet digital PCR), both of whose performance has previously been evaluated., Results: Significant evidence of exponential amplification (R 2  > 0.99) and final fluorescence > 0.15 were combined for thresholding. This objective approach identified a population of positive samples, however there were a subset of samples that amplified towards the end of the cycling protocol (at or later than 35 cycles), which were less clearly defined. The Fast-Track Vaginal swab assay showed good sensitivity against the commercial (95.71) and non-commercial (97.18) tests. Specificity was lower against both (90.00 and 96.55, respectively)., Conclusions: This study defined a simple, automated protocol for binary classification of continuous, real-time qPCR data, for use in an end-point diagnostic test. This method identified a population of positive samples, however, as with manual thresholding, a subset of samples that amplified towards the end of the cycling program were less easily classified. When used with ocular swabs, the Fast-Track Vaginal swab assay had good sensitivity for C. trachomatis detection, but lower specificity than the commercial and non-commercial assays it was evaluated against, possibly leading to false positives.

Background: Trachoma is targeted for elimination by 2020. World Health Organization advises districts to undertake surveillance when follicular trachoma (TF) <5% in children 1-9 years and mass antibiotic administration has ceased. There is a question if other tools could be used for surveillance as well. We report data from a test for antibodies to C. trachomatis antigen pgp3 as a possible tool., Methodology: We randomly sampled 30 hamlets in Kilosa district, Tanzania, and randomly selected 50 children ages 1-9 per hamlet. The tarsal conjunctivae were graded for trachoma (TF), tested for C. trachomatis infection (Aptima Combo2 assay: Hologic, San Diego, CA), and a dried blood spot processed for antibodies to C. trachomatis pgp3 using a multiplex bead assay on a Luminex 100 platform., Principal Findings: The prevalence of trachoma (TF) was 0.4%, well below the <5% indicator for re-starting a program. Infection was also low, 1.1%. Of the 30 hamlets, 22 had neither infection nor TF. Antibody positivity overall was low, 7.5% and increased with age from 5.2% in 1-3 year olds, to 9.3% in 7-9 year olds (p = 0.015). In 16 of the 30 hamlets, no children ages 1-3 years had antibodies to pgp3., Conclusions: The antibody status of the 1-3 year olds indicates low cumulative exposure to infection during the surveillance period. Four years post MDA, there is no evidence for re-emergence of follicular trachoma.

Ocular swabs from Tanzania were tested for Chlamydia trachomatis (CT), and self-collected vaginal swabs collected through a home collection program, iwantthekit.org, were tested for Neisseria gonorrhoeae and CT to evaluate Cepheid GeneXpert for the use of pooling multiple specimens before testing. GeneXpert shows to be a promising test for pooling., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Trachoma, caused by repeated infections with ocular Chlamydia trachomatis, is targeted for elimination using multiple annual rounds of mass drug administration (MDA) in endemic communities. Infection rates do not decline as expected in some communities, leading to concerns about azithromycin resistance., Methods: After 3 yearly MDAs in 32 communities in Tanzania, 107 children were identified 1 year later with infection. All were provided MDA again, and 90 were seen again at 2 months, of whom 30 had infection. Chlamydia trachomatis isolates were obtained before and after MDA in 15 paired samples and were tested for antimicrobial susceptibility. The infectious load of C. trachomatis before MDA was determined in 30 children who had infection at both times and 60 whose infection cleared., Results: The median load was 8.6 genome copies per polymerase chain reaction in the consistently infected, and 8.4 in those whose infection cleared (P = .86). For the consistently infected, the average minimum inhibitory concentration was 0.26 µg/mL for azithromycin before and 0.20 µg/mL after MDA. All isolates had minimum inhibitory concentration ≤0.50 µg/mL., Conclusions: There is no evidence that continued infection after MDA was due either to resistance to azithromycin or to a heavier load of organism before treatment. Other potential causes of persistent infection need to be evaluated.

Purpose: We detected spatial clustering of households with Chlamydia trachomatis infection (CI) and active trachoma (AT) in villages undergoing mass treatment with azithromycin (MDA) over time., Methods: We obtained global positioning system (GPS) coordinates for all households in four villages in Kongwa District, Tanzania. Every 6 months for a period of 42 months, our team examined all children under 10 for AT, and tested for CI with ocular swabbing and Amplicor. Villages underwent four rounds of annual MDA. We classified households as having ≥1 child with CI (or AT) or having 0 children with CI (or AT). We calculated the difference in the K function between households with and without CI or AT to detect clustering at each time point., Results: Between 918 and 991 households were included over the 42 months of this analysis. At baseline, 306 households (32.59%) had ≥1 child with CI, which declined to 73 households (7.50%) at 42 months. We observed borderline clustering of households with CI at 12 months after one round of MDA and statistically significant clustering with growing cluster sizes between 18 and 24 months after two rounds of MDA. Clusters diminished in size at 30 months after 3 rounds of MDA. Active trachoma did not cluster at any time point., Conclusions: This study demonstrates that CI clusters after multiple rounds of MDA. Clusters of infection may increase in size if the annual antibiotic pressure is removed. The absence of growth after the three rounds suggests the start of control of transmission., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Purpose: 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., Conclusions/significance: 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.

Objective: The goal of this study was to determine the prevalence of vaginitis and its association with high-risk human papillomavirus (HR HPV) in women undergoing cervical cancer screening in rural Tanzania., Methods: For the purpose of cervical cancer screening, cytology and HR HPV polymerase chain reaction data were collected from 324 women aged between 30 and 60 years. Microscopy and gram stains were used to detect yeast and bacterial vaginosis. Cervical nucleic acid amplification test specimens were collected for the detection of Trichomonas vaginalis (TV), Chlamydia trachomatis, and Neisseria gonorrhoeae., Results: The majority of women were married (320 of 324) and reported having a single sexual partner (270 of 324); the median age of participants was 41 years. HR HPV was detected in 42 participants. Forty-seven percent of women had vaginitis. Bacterial vaginosis was the most common infection (32.4%), followed by TV (10.4%), and yeast (6.8%). In multivariable logistic regression analysis, TV was associated with an increased risk of HR HPV (odds ratio, 4.2 [95% CI, 1.7-10.3]). Patients with TV were 6.5 times more likely to have HPV type 16 than patients negative for TV (50% vs 13.3%) (odds ratio, 6.5 [95% CI, 1.1-37])., Conclusions: Among rural Tanzanian women who presented for cervical cancer screening, Trichomonas vaginitis was significantly associated with HR HPV infection (specifically type 16)., (© 2014 Published by Elsevier HS Journals, Inc.)

Purpose: To determine the sensitivity, specificity, and field utility of the Cepheid GeneXpert Chlamydia trachomatis (CT) Assay (GeneXpert) for ocular chlamydia infection compared to Roche Amplicor CT assay (Amplicor)., Methods: In a trachoma-endemic community in Kongwa Tanzania, 144 children ages 0 to 9 were surveyed to assess clinical trachoma and had two ocular swabs taken. One swab was processed at Johns Hopkins University, Baltimore MD, using Amplicor, (Roche Molecular Diagnostics) and the other swab was processed at a field station in Kongwa using the GeneXpert Chlamydia trachomatis/Neisseria gonorrhoeae assay (Cepheid). The sensitivity and specificity of GeneXpert was compared to the Amplicor assay., Results: Of the 144 swabs taken the prevalence of follicular trachoma by clinical exam was 43.7%, and by evidence of infection according to Amplicor was 28.5%. A total of 17 specimens (11.8%) could not be processed by GeneXpert in the field due to lack of sample volume, other specimen issues or electricity failure. The sensitivity of GeneXpert when compared to Amplicor was 100% and the specificity was 95%. The GeneXpert test identified more positives in individuals with clinical trachoma than Amplicor, 55% versus 52%., Conclusion: The GeneXpert test for C. trachomatis performed with high sensitivity and specificity and demonstrated excellent promise as a field test for trachoma control.

The GeneXpert CT/NG assay (GeneXpert) and the Abbott m2000 RealTime CT (m2000) assay were compared to Amplicor for detecting ocular Chlamydia trachomatis. Discordant specimens were tested by the Aptima CT assay. The m2000 assay sensitivity was 100% (95% confidence interval [CI], 90% to 100%), and specificity was 98.46% (95% CI, 95.2% to 99.2%); GeneXpert sensitivity was 100% (95% CI, 90% to 100%), and specificity was 100% (95% CI, 98.1% to 100%). The m2000 and GeneXpert assays appear to perform as well as the Amplicor assay.

In disease control or elimination programs, diagnostics are essential for assessing the impact of interventions, refining treatment strategies, and minimizing the waste of scarce resources. Although high-performance tests are desirable, increased accuracy is frequently accompanied by a requirement for more elaborate infrastructure, which is often not feasible in the developing world. These challenges are pertinent to mapping, impact monitoring, and surveillance in trachoma elimination programs. To help inform rational design of diagnostics for trachoma elimination, we outline a nonparametric multilevel latent Markov modeling approach and apply it to 2 longitudinal cohort studies of trachoma-endemic communities in Tanzania (2000-2002) and The Gambia (2001-2002) to provide simultaneous inferences about the true population prevalence of Chlamydia trachomatis infection and disease and the sensitivity, specificity, and predictive values of 3 diagnostic tests for C. trachomatis infection. Estimates were obtained by using data collected before and after mass azithromycin administration. Such estimates are particularly important for trachoma because of the absence of a true "gold standard" diagnostic test for C. trachomatis. Estimated transition probabilities provide useful insights into key epidemiologic questions about the persistence of disease and the clearance of infection as well as the required frequency of surveillance in the post-elimination setting.

Importance: The World Health Organization recommends at least 3 annual mass drug administrations (MDAs) of azithromycin in places where the prevalence of follicular trachoma (FT) is greater than 10%. However, stopping MDA prior to 3 rounds, if monitoring indicates an absence of infection with Chlamydia trachomatis even if FT persists, may be more cost-effective., Objective: To determine the prevalence of infection in communities randomized to 3 rounds of annual MDAs with azithromycin compared with communities randomized to a stopping rule, where MDA could cease if the infection rate was low. DESIGN A 1:1 community randomized trial comparing usual care with a cessation rule. The Partnership for the Rapid Elimination of Trachoma-Ziada Trial was conducted from February 1, 2010, through September 1, 2011., Setting: Sixteen communities in Tanzania with trachoma prevalence rates between 10% and 20%., Participants: A total of 100 children aged 5 years or younger randomly drawn from each community. Children had to reside in an eligible community, have no ocular condition that prevented trachoma grading or ocular specimen collection, and have a guardian who could provide consent for participation., Interventions: Cessation of MDA with azithromycin if the community had no infection in their sample at 6 months or 18 months., Main Outcome Measure: The prevalence of C trachomatis at 18 months., Results: None of the intervention communities met criteria to stop MDA based on the 6-month or 18-month survey; all, as well as the usual care communities, were scheduled for a third MDA round. There was no difference in infection (2.9% vs 4.7%; P = .25) between the usual care and cessation rule communities at 18 months., Conclusions and Relevance: In this setting, communities with low (10%-20%) initial prevalence of active trachoma did not have MDA stopped before 3 annual rounds on the basis of monitoring for infection. Infection with C trachomatis in communities with average trachoma rates at 12% to 13% cannot be eliminated before 3 rounds of MDA with azithromycin., Trial Registration: clinicaltrials.gov Identifier: NCT00792922.

Purpose: To determine whether 2-day dosing of azithromycin may improve the efficacy of azithromycin dosing in children with severe trachoma., Methods: Fifty children with severe trachoma (defined as either trachoma intense or follicular trachoma with ten or more follicles) were enrolled from five villages in Kongwa, Tanzania. Enrollment occurred within 1 month and within the same district as the historical control population of 99 children with severe trachoma, all of whom received 1-day dosing. Baseline data on age, sex, and trachoma status were obtained, and swabs for determination of Chlamydia trachomatis were taken. All 50 children received 20 mg/kg azithromycin daily for 2 days, which was directly observed. Children were followed up at 6 weeks for trachoma and infection. The laboratory was masked to treatment assignment., Results: Baseline characteristics were similar between the treatment group and the control group. A total of 1/46 (2.2%) of children in the treatment group were polymerase chain reaction (PCR)-positive at 6 weeks, a 96.3% reduction from baseline, compared to 13/96 (13.5%) in the historical control group, an 89.4% reduction. This difference was statistically significant. However when modeled using logistic regression and accounting for age, gender, weight, and baseline percent PCR positivity, the difference was not significant. Prevalence of clinical trachoma did not differ between the groups at 6 weeks., Conclusion: For children with severe trachoma, a randomized controlled trial of 2-day versus 1-day treatment may be warranted.

Purpose: 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., Methods: 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)., Results: 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)., Conclusions: 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.

Background: The World Health Organization recommends mass treatment as part of a trachoma control strategy. However, scant empirical data from hyperendemic communities exist on the number of rounds of treatment needed to reach a goal of <5% prevalence in children. We determined the prevalence of trachoma and infection with Chlamydia trachomatis in communities after 3-7 years of annual mass treatment in Tanzania., Methods: Seventy-one communities with trachoma and annual azithromycin coverage data were enrolled. A cross-sectional survey of ≥100 randomly selected children aged <5 years in each community was performed. Children were examined for clinical trachoma, and swab samples were taken for determination of ocular C. trachomatis infection., Results: After 3 years of mass treatment, the prevalence of trachoma decreased in a linear fashion with number of years of mass treatment, whereas decreased prevalences of C. trachomatis infection were related to the extent of the previous year's azithromycin coverage. Our model suggests that, for communities with baseline trachoma prevalence of 50% and annual treatment coverage of 75%, >7 years of annual mass treatment will be needed to reach a prevalence of trachoma of <5%., Conclusions: Country programs in trachoma-endemic regions must realistically expect that several years of annual mass treatment may be necessary to eliminate trachoma.

Background: Trachoma is the leading infectious cause of blindness in the world, and for endemic communities, mass treatment with azithromycin reduces the pool of infection. High coverage is essential, especially in children as they are the infectious reservoir. However, infection remains post-mass treatment. We sought to determine risk factors for infection in children post-mass treatment., Methodology: All children under 9 years in 4 villages in Tanzania were followed from baseline pre-mass treatment to six months post treatment. 1,991 children under nine years were enrolled in the longitudinal study and data on individual and household characteristics was collected at baseline. Clinical trachoma was determined by an ocular exam and infection detected by PCR of an eyelid swab. Azithromycin was offered and infection was reassessed at 6 months. A multilevel logistic regression model was used, accounting for household clustering of children for analysis., Principal Findings: Baseline infection was 23.7% and at 6 months was 10.4%, despite 95% coverage. Infection at baseline was positively associated with infection at 6 months (OR = 3.31, 95%CI 2.40-4.56) and treatment had a protective effect (OR = 0.45, 95%CI 0.25-0.80). The age group 2-4 years had an increased risk of infection at 6 months. The household characteristics predictive of infection at 6 months were increasing number of children infected in the household at baseline and increasing number of untreated children in the household., Conclusions: While one round of mass treatment with high coverage did decrease infection by over 50%, it appears that it is not sufficient to eliminate infection. Findings that young children (ages 2-4 years) and households with increasing numbers of infected and untreated children have a positive association with infection at 6 months suggest that such households could be targeted for more intensive follow up.

Background: 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., Conclusions/significance: 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: ClinicalTrials.gov NCT00792922.

Background: Mass drug administration (MDA) is part of the current trachoma control strategy, but it can be costly and results in many uninfected individuals receiving treatment. Here we explore whether alternative, targeted approaches are effective antibiotic-sparing strategies., Methodology/principal Findings: We analysed data on the prevalence of ocular infection with Chlamydia trachomatis and of active trachoma disease among 4,436 individuals from two communities in The Gambia (West Africa) and two communities in Tanzania (East Africa). An age- and household-structured mathematical model of transmission was fitted to these data using maximum likelihood. The presence of active inflammatory disease as a marker of infection in a household was, in general, significantly more sensitive (between 79% [95%CI: 60%-92%] and 86% [71%-95%] across the four communities) than as a marker of infection in an individual (24% [16%-33%]-66% [56%-76%]). Model simulations, under the best fit models for each community, showed that targeting treatment to households has the potential to be as effective as and significantly more cost-effective than mass treatment when antibiotics are not donated. The cost (2007US$) per incident infection averted ranged from 1.5 to 3.1 for MDA, from 1.0 to 1.7 for household-targeted treatment assuming equivalent coverage, and from 0.4 to 1.7 if household visits increased treatment coverage to 100% in selected households. Assuming antibiotics were donated, MDA was predicted to be more cost-effective unless opportunity costs incurred by individuals collecting antibiotics were included or household visits improved treatment uptake. Limiting MDA to children was not as effective in reducing infection as the other aforementioned distribution strategies., Conclusions/significance: Our model suggests that targeting antibiotics to households with active trachoma has the potential to be a cost-effective trachoma control measure, but further work is required to assess if costs can be reduced and to what extent the approach can increase the treatment coverage of infected individuals compared to MDA in different settings.

Objectives: To determine prevalence of, and risk factors for, bacterial vaginosis (BV) among herpes simplex virus (HSV) 2 seropositive Tanzanian women at enrollment into a randomised, placebo-controlled trial of HSV suppressive treatment., Methods: 1305 HSV-2 seropositive women aged 16-35 years working in bars, guesthouses and similar facilities were interviewed, examined and tested for HIV, syphilis, Neisseria gonorrhoeae, Chlamydia trachomatis, BV, candidiasis and trichomoniasis. Factors associated with BV were analysed using logistic regression to estimate odds ratios and 95% confidence intervals., Results: BV prevalence was 62.9%; prevalence of Nugent score 9-10 was 16.1%. Independent risk factors for BV were work facility type, fewer dependents, increasing alcohol consumption, sex in the last week (adjusted OR 2.03; 95% CI 1.57 to 2.62), using cloths or cotton wool for menstrual hygiene, HIV (adjusted OR 1.41; 95% CI 1.09 to 1.83) and Trichomonas vaginalis infection. There was no association between BV and the frequency or method of vaginal cleansing. However, BV was less prevalent among women who reported inserting substances to dry the vagina for sex (adjusted OR 0.44; 95% CI 0.25 to 0.75)., Conclusion: BV was extremely prevalent among our study population of HSV-2 positive female facility workers in North-western Tanzania. Although recent sex was associated with increased BV prevalence, vaginal drying was associated with lower BV prevalence. Further studies of the effects of specific practices on vaginal flora are warranted.

Trachoma, a blinding eye disease caused by repeated and prolonged infection with Chlamydia trachomatis, is a significant public health problem for sub-Saharan Africa. Tanzania has had a National Trachoma Task Force since 1999, working on trachoma control in endemic districts. The objective of this study was twofold: first, to determine the current status of infection and clinical trachoma in these districts in Tanzania, and second, to determine if a combination of clinical signs could be used as a surrogate for infection. We conducted a survey for trachoma and infection with C. trachomatis in 75 villages in eight districts of Kongwa, Kilosa, Mpwapwa, Bahi, Kondoa, Manyoni, Monduli and Iramba in Tanzania, which have previously been shown to be endemic. In each village, a random sample of households, and of children within households, was taken for examination. Trachoma was graded using the World Health Organization system, which we expanded, and a swab taken to determine presence of infection. The rates of trachoma ranged from 0% in Iramba District to 15.17% in Monduli District, with large variation in villages within districts. Infection rates were generally lower than trachoma rates, as expected, and most districts had villages with no infection. A combination of clinical signs of trachoma in children, when absent, showed very high specificity for identifying villages with no infection. We conclude that these signs might be useful for monitoring absence of infection in villages, and that districts with trachoma prevalence between 10% and 15% should have village level rapid surveys to avoid unnecessary mass treatment.

Background: Trachoma, the worldwide leading infectious cause of blindness, is due to repeated conjunctival infection with Chlamydia trachomatis. The effects of control interventions on population levels of infection and active disease can be promptly measured, but the effects on severe ocular sequelae require long-term monitoring. We present an age-structured mathematical model of trachoma transmission and disease to predict the impact of interventions on the prevalence of blinding trachoma., Methodology/principal Findings: The model is based on the concept of multiple reinfections leading to progressive conjunctival scarring, trichiasis, corneal opacity and blindness. It also includes aspects of trachoma natural history, such as an increasing rate of recovery from infection and a decreasing chlamydial load with subsequent infections that depend upon a (presumed) acquired immunity that clears infection with age more rapidly. Parameters were estimated using maximum likelihood by fitting the model to pre-control infection prevalence data from hypo-, meso- and hyperendemic communities from The Gambia and Tanzania. The model reproduces key features of trachoma epidemiology: 1) the age-profile of infection prevalence, which increases to a peak at very young ages and declines at older ages; 2) a shift in this prevalence peak, toward younger ages in higher force of infection environments; 3) a raised overall profile of infection prevalence with higher force of infection; and 4) a rising profile, with age, of the prevalence of the ensuing severe sequelae (trachomatous scarring, trichiasis), as well as estimates of the number of infections that need to occur before these sequelae appear., Conclusions/significance: We present a framework that is sufficiently comprehensive to examine the outcomes of the A (antibiotic) component of the SAFE strategy on disease. The suitability of the model for representing population-level patterns of infection and disease sequelae is discussed in view of the individual processes leading to these patterns.

Background: Children with a heavy load of C. trachomatis infection may continue to be infected following a single dose of 20 mg/kg of azithromycin. We compared the C. trachomatis infection rates at six weeks post-treatment of children randomized to 30 mg/kg single dose of azithromycin versus 20 mg/kg single dose of azithromycin., Methods: Ninety-nine children with severe trachoma (defined as either trachoma intense or follicular trachoma with ten or more follicles) were enrolled and randomly assigned. Baseline data on age, sex, and trachoma status was obtained, and swabs for determination of C. trachomatis were taken. Dosing was weight-based and observed. Children were followed up at six weeks for trachoma and infection. The laboratory was masked to treatment assignment., Results: Both groups experienced reductions in infection and in severe trachoma. Twelve percent of the 20 mg/kg group were PCR positive at 6 weeks, compared with 69% at baseline, an 82% reduction (p-value < .001). In the 30 mg/kg group, 15% were infected, compared with 62% at baseline, a 76% reduction (p < .001). The rate of infection comparing treatment groups was not significantly different at 6 weeks (p = 0.71). Analyses on children who were infected at baseline showed those remaining positive at six weeks were 18%, and 14% in the standard and high dose groups, respectively., Conclusion: Increasing the single dose of azithromycin to 30 mg/kg in children with severe trachoma did not result in significantly less infection at six weeks post-treatment compared to 20 mg/kg.

Objective: Clinically, constant severe trachoma predicts an increased risk of scarring in children. There are no data on the risk of scarring associated with constant infection with Chlamydia trachomatis, regardless of clinical manifestation. We propose to determine the 5-year incidence of scarring in children with a history of constant severe trachoma, constant infection, or both compared with children who had a history of neither., Design: A 5-year, longitudinal observational study., Participants: Children aged less than 10 years with data on trachoma and infection for 3 of the 5 visits in the first 18 months, and follow-up 5-year data on scarring., Methods: Data were collected on clinical trachoma, and ocular swabs were taken to determine the presence of C. trachomatis in children in a hyperendemic village in Tanzania. Images were graded for scarring. Data were collected at baseline; 2, 6, 12, and 18 months; and 5 years from baseline. Severe trachoma was defined as the presence of 10 or more follicles, or trachoma intense. A child had constant infection (severe trachoma) if infection (severe trachoma) was present on at least 3 visits before the 5-year survey., Main Outcome Measures: Five-year risk of scarring., Results: Of the 189 children, 22 (11.6%) had constant severe trachoma, but not constant infection. Nine children (4.8%) had constant infection but not constant severe trachoma. Both constant severe trachoma and constant infection were present in 16 children (8.5%). The 5-year incidence of scarring was similar in all 3 groups; children with constant severe trachoma only, with constant infection only, and with both were most likely to develop scars (35.0%, 44.4%, 31.2%, respectively) compared with those with sporadic trachoma or infection (15.2%) or neither (6.8%) (P = 0.0002)., Conclusions: Children with constant infection are also likely to have constant severe trachoma, and their 5-year risk of scarring is high compared with children with sporadic severe trachoma or infection. These data further support the presence of a subgroup of children who cannot clear infection with C. trachomatis, who may manifest a severe immunologic response to infection, and who are at increased risk of scarring sequelae., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Purpose: The World Health Organization recommends mass treatment of trachoma-hyperendemic communities, but there are scant empiric data on the number of rounds of treatment that are necessary for sustainable reductions. The rates of active trachoma and infection with C. trachomatis were determined in a community 3.5 years after two rounds of mass treatment with azithromycin., Methods: Maindi village in Tanzania received a first round of mass treatment with azithromycin after a baseline survey for trachoma and infection. All residents aged 6 months and older were offered single-dose treatment with azithromycin (excluding pregnant women with no clinical trachoma, who were offered topical tetracycline). The residents were followed over an 18-month period, and, according to similar treatment criteria, were offered retreatment at 18 months. Five years after baseline (3.5 years after the second round of mass treatment), a new census and survey of current residents for trachoma and infection was conducted. Children are the sentinel markers of infection and trachoma in communities, so data are presented specifically for ages 0 to 7 years (preschool age) and 8 to 16 years., Results: Treatment coverage was above 80% for all ages in the first round, and highest (90%) in preschool-aged children. Second-round coverage was lower, <70%, and 70% in preschool-aged children. At 5 years, trachoma rates were still lower than baseline, ranging from 45% in those aged 0 to 3 years to 8% in those aged 11 to 15 years (compared with 81% and 39% at baseline, respectively). Infection rates at baseline ranged from 71% to 57%, but were 27% to 17% at 5 years after two rounds of mass treatment. At 5 years, there were no differences in trachoma or infection rates, when comparing new residents who came after the second mass treatment with those who had been resident in the village during both rounds (P > 0.05). Infection rates were lower in those who had been treated twice or at 18 months than in those treated only at baseline or never treated., Conclusions: Although mass treatment appears to be associated with lower disease and infection rates in the long term, trachoma and C. trachomatis infection were not eliminated in this trachoma hyperendemic village 3.5 years after two rounds of mass treatment. Continued implementation of the SAFE strategy in this environment is needed.

Background: There are no data on the cumulative effect of fly control and antibiotic distribution on trachoma in hyperendemic communities. We sought to determine whether insecticide spray intervention after mass antibiotic treatment could reduce trachoma and ocular infection with Chlamydia trachomatis in hyperendemic neighbourhoods in Tanzania., Methods: We did a single-blind, randomised clinical trial in 16 neighbourhoods (balozi) in Kongwa, Tanzania. All children aged 1-7 years were enrolled, with 119 children in the eight balozi of the intervention group and 183 in the eight control balozi. Children were examined at baseline, 6 months, and 1 year for clinical trachoma and ocular C trachomatis infection. One dose of azithromycin was offered to all residents of both intervention and control balozi after the baseline survey. Households (and surrounding areas) in the intervention group were then sprayed with insecticide throughout the ensuing year and monitored for reductions in fly counts. This study is registered at ClinicalTrials.gov, number NCT00347763., Findings: The intervention balozi had significantly lower fly counts than controls at all monitored weeks (p<0.05), apart from weeks 7-9. The trachoma rate did not differ significantly in the intervention and control balozi at 6 months post-treatment (20%vs 33%, p=0.07), nor did it at 1 year (43%vs 44%, p=0.90). Infection with C trachomatis did not differ between groups at 6 months post-treatment (9%vs 7%, p=0.45)., Interpretation: Intensive insecticide spraying reduced flies in the environment, but our results suggest that fly reduction after mass antibiotic treatment has no added benefit on reduction of trachoma.

Purpose: To observe the spatial distribution of households with high loads of ocular chlamydia infection in children, before and after mass treatment with azithromycin to determine whether there exists spatial clustering of households with high loads of infection and the spatial scale of the clustering., Methods: All residents of a village in Tanzania were invited to participate in the study. A global positioning system unit recorded the location of each house. Mass treatment with azithromycin was offered, with participation above 80%. Active trachoma and swab samples of the conjunctiva were assessed at baseline and at 2, 6, 12, and 18 months after treatment. A k-function analysis was performed to detect clustering of households with high loads of ocular chlamydia in children younger than 8 years., Results: A total of 1055 villagers were examined during the study; of these, 374 (35.4%) were children younger than 8 years. The total number of households was 215, with 182 (84.6%) households having at least one child. K-function analysis showed clustering of households with high loads of ocular chlamydia at distances up to 2 kilometers (km) at baseline; at 6 months, slight clustering existed within 0.5 km. At 12 and 18 months, high load households clustered at distances up to 1.3 km., Conclusions: This analysis suggests that infection spreads between households with children or that nearby households share the same risk factors for infection. Mass treatment has value in lowering infection prevalence within the community, and clustering of households with infection takes up to 1 year to reemerge at the same level as baseline. Re-treatment at yearly intervals may interrupt spread of infection.

Objective: To evaluate the pattern of recurrence of trachomatous trichiasis (TT) after bilamellar tarsal rotation surgery for trachoma., Design: Observational cohort., Participants: Three hundred eighty-four participants having at least 1 eye that had undergone a single TT surgery a minimum of 18 months before June 2001. The 630 study eyes were divided equally between left (311) and right (319) eyes., Methods: Patients living in Central Tanzania were identified from surgical lists. Participants were screened for recurrence of TT, including evidence of epilation, after surgery., Main Outcome Measures: Detailed information on the location of recurrence was collected, including number of lashes touching the globe and location of trichiatic lashes (nasal, central, or temporal)., Results: One hundred seventy-six eyes had evidence of TT recurrence (28%), including 23 eyes having recently undergone epilation. In eyes without epilation, left eyes had a higher rate of recurrence than right eyes (32% vs. 25%; P = 0.05). Among eyes with recurrence originating from 1 location, recurrence was highest centrally (40%). Right eyes had nasal recurrence more often than temporal recurrence (33% vs. 20%). Left eyes had temporal recurrence more often than nasal recurrence (41% vs. 24%)., Conclusions: Recurrence of TT after surgery is more common in the left eye and on the left side of the eyelid. The surgical procedure is more difficult to perform on the right side of the eyelid by a right-handed surgeon. This difficulty may lead to an unintentional change in surgical technique on the right, which may result in lower recurrence on that side.

Quantitative PCR (Q-PCR) technology has recently been applied to the measurement of ocular loads of Chlamydia trachomatis. We present an index called the community ocular C. trachomatis load (COCTL) which is similar to the community microfilarial load (CMFL) of onchocerciasis. Our index has the advantage of being scale-independent so that, for example, percentage changes are the same whether calculated per eye swab or per Q-PCR capillary. The COCTL for a population or subgroup is formed by adding the arbitrary concentration of 1 organism per ml to each individual Q-PCR quantification, calculating the geometric mean, and finally subtracting 1 per ml again. The use of the COCTL is illustrated in a study of trachoma in northern Tanzania. The COCTL is higher in people with clinical trachoma than those without (5.8 organisms per swab vs. 0.1), and in children aged six months to ten years than in the overall population (1.1 vs. 0.4). The COCTL index is potentially useful for sentinel sites, operational research and calibration of clinical measures of trachoma.

Purpose: The World Health Organization recommends trichiasis surgery to prevent blindness caused by trachoma; however, recurrence is common. Risk factors for recurrence have not been widely studied, particularly in trachoma hyperendemic areas., Methods: Three hundred ninety-four persons with trichiasis in Tanzania were examined. Participants had undergone surgery >18 months before the study. Trichiasis recurrence and active trachoma at study visit were assessed. Ocular swabs were collected and tested for Chlamydia trachomatis. Household members were examined for active trachoma., Results: Of the surgical eyes, 28% had recurrence; 40% of patients had recurrence in one or both eyes. Rates did not vary by time since surgery. Eye-level recurrence rates varied significantly across districts, ranging from 16% to 38%. Current chlamydial infection among surgical cases was low (6%) and was not associated with recurrence. Recurrence was associated with tarsal conjunctival inflammation (OR: 2.4; 95% confidence interval [CI]: 1.6-3.8) and residence in the Kongwa district (OR: 2.3; 95% CI: 1.2-4.6)., Conclusions: Recurrence after trichiasis surgery is high, suggesting that vigilant follow-up in surgical cases is needed to reduce blindness. Recurrence is associated with evidence of inflammation in the tarsal conjunctiva, although it is not clear whether the inflammation contributes to recurrence, or is a result of the recurrence. Longitudinal studies of trichiasis patients after surgery are needed.

Purpose: Trachoma remains a leading cause of blindness. Determining the most effective antibiotic treatment strategy is essential for the success of country-based trachoma control programs., Methods: Baseline and 2-month follow-up examinations were performed in a trachoma-hyperendemic village. All residents were offered azithromycin for trachoma after baseline was determined. Infection with Chlamydia trachomatis and chlamydial load were determined by PCR. Clinical trachoma status was evaluated. A high chlamydial load was defined as a higher than median chlamydial load among those with infection. Risk factors were examined in multiple logistic regression models. Associations are presented as odds ratios and 95% confidence intervals., Results: At baseline, 57% of participants were infected with C. trachomatis. Although clinical trachoma correlated with infection, 23% of participants with high chlamydial loads showed no clinical signs. Adults represented only 10% of the population with high loads. Treatment significantly decreased the proportion positive in the community and the load in the community. However, 27% of individuals with high loads at baseline who received treatment also were infected at 2 months. Of those, 93% with high loads at 2 months were aged < or =10 years., Conclusions: Although most of the chlamydial load in this community resided in children, 10% of the high load resided in adults, most of whom did not have follicular trachoma and in whom the infection would be missed under treatment strategies that focus on clinical disease or children. These data support a mass treatment strategy for hyperendemic communities, at least as a first approach. In addition, treatment of children age < or =2 years should be reexamined, as >30% with high loads at baseline remained infected at 2 months, despite monitored treatment according to weight.

Background: Trachoma, caused by repeated ocular infection with Chlamydia trachomatis, is an important cause of blindness. Current recommended dosing intervals for mass azithromycin treatment for trachoma are based on a mathematical model., Methods: We collected conjunctival swabs for quantitative polymerase-chain-reaction assay of C. trachomatis before and 2, 6, 12, 18, and 24 months after mass treatment with azithromycin in a Tanzanian community in which trachoma was endemic. For ethical reasons, at 6, 12, and 18 months, we gave tetracycline eye ointment to residents who had clinically active trachoma., Results: At baseline, 956 of 978 residents (97.8 percent) received either one oral dose of azithromycin or (if azithromycin was contraindicated) a course of tetracycline eye ointment. The prevalence of infection fell from 9.5 percent before mass treatment to 2.1 percent at 2 months and 0.1 percent at 24 months. The quantitative burden of ocular C. trachomatis infection in the community was 13.9 percent of the pretreatment level at 2 months and 0.8 percent at 24 months. At each time point after baseline, over 90 percent of the total community burden of C. trachomatis infection was found among subjects who had been positive the previous time they were tested., Conclusions: The prevalence and intensity of infection fell dramatically and remained low for two years after treatment. One round of very-high-coverage mass treatment with azithromycin, perhaps aided by subsequent periodic use of tetracycline eye ointment for persons with active disease, can interrupt the transmission of ocular C. trachomatis infection., (Copyright 2004 Massachusetts Medical Society.)

Background: Antibiotics are an important part of WHO's strategy to eliminate trachoma as a blinding disease by 2020. At present, who needs to be treated is unclear. We aimed to establish the burden of ocular Chlamydia trachomatis in three trachoma-endemic communities in Tanzania and The Gambia with real-time quantitative PCR., Methods: Conjunctival swabs were obtained at examination from 3146 individuals. Swabs were first tested by the qualitative Amplicor PCR, which is known to be highly sensitive. In positive samples, the number of copies of omp1 (a single-copy C trachomatis gene) was measured by quantitative PCR., Findings: Children had the highest ocular loads of C trachomatis, although the amount of pooling in young age groups was less striking at the site with the lowest trachoma frequency. Individuals with intense inflammatory trachoma had higher loads than did those with other conjunctival signs. At the site with the highest prevalence of trachoma, 48 of 93 (52%) individuals with conjunctival scarring but no sign of active disease were positive for ocular chlamydiae., Interpretation: Children younger than 10 years old, and those with intense inflammatory trachoma, probably represent the major source of ocular C trachomatis infection in endemic communities. Success of antibiotic distribution programmes could depend on these groups receiving effective treatment.

Risk factors for the incidence of scarring are needed to inform trachoma control programs in countries hyperendemic for this blinding disease. A cohort of pre-school children with constant, severe trachoma, and an age, sex, and neighborhood matched cohort of children without constant severe trachoma were followed for seven years to determine the incidence of scarring. The incidence of scarring in the children with constant severe trachoma was 29.2% versus 9.6% in the comparison group. In a model adjusting for multiple factors, significant predictors of scarring were increasing age, female, and constant severe trachoma (OR = 4.85, 95% CL = 2.05, 11.40). Infection with C. trachomatis at follow up was also associated with scarring in both groups of children. It is likely that these children have a different host response to infection, and represent a subgroup at high risk for the blinding complications of trachoma. Reducing exposure to infection in the community through antibiotics and changes in hygiene practices is still the most promising control strategy.

A six-year prospective study of Chlamydia trachomatis infection and ocular disease in Tanzanian village children was conducted to identify the determinants of trachoma endemicity using sequencing of ompA. Overall, 749 conjunctival samples were obtained, with 176 children sampled in both 1989 and 1995. 31.1% (233/749) were positive by PCR-enzyme immunoassay, and 76% (176/233) of the positives were sequenced in variable domains (VD) 1 to 4 (22 children in both 1989 and 1995). Twenty-six ompA genotypes of serovar A, and 19 of B/Ba were identified, and only 20% of genotypes identified in 1995 matched those found in 1989. In particular, B/Ba genotypes exhibited a 15-base region in VD 2 with increased nucleotide substitution, and these types were associated with age and water availability. Homotypic infection and infection with multiple genotypes and high chlamydial load did predict subsequent severe trachoma (odds ratio (OR) = 10.14, 95% confidence interval (CI): 1.71, 60.23; OR = 6.40, 95% CI: 0.75, 54.41; OR = 6.74, 95% CI: 0.82, 55.38, respectively). And, multitypic infection was clustered with residence of village and associated with familial cattle ownership. In conclusion, high ompA polymorphism and the inability of some hosts to clear infection with the same ompA genotype suggest two distinct but converging mechanisms of endemic severe trachoma.

Objective: To measure the prevalence of urethritis due to Neisseria gonorrhoeae and Chlamydial infection trachomatis in rural Tanzanian men, Design: About 500 men aged 15-54 years were selected from each of 12 rural communities by random cluster sampling; interviewed concerning past or present symptoms of sexually transmitted diseases; and asked to provide a first catch urine specimen, which was tested for pyuria with a leucocyte esterase dipstick test. Subjects with symptoms or with a positive result on testing were examined, and urethral swabs were taken for detection of N gonorrhoeae by gram stain and of C trachomatis by antigen detection immunoassay., Setting: Mwanza region, north western Tanzania., Subjects: 5876 men aged 15-54 years., Main Outcome Measures: Prevalence of urethral symptoms, observed urethral discharge, pyuria, urethritis ( > 4 pus cells per high power field on urethral smear), N gonorrhoeae infection (intracellular gram negative diplococci), and C trachomatis infection (IDEIA antigen detection assay)., Results: 1618 (28%) subjects reported ever having a urethral discharge. Current discharge was reported by 149 (2.5%) and observed on examination in 207 (3.5%). Gonorrhoea was found in 128 subjects (2.2%) and chlamydial infection in 39 (0.7%). Only 24 of 158 infected subjects complained of urethral discharge at the time of interview (15%)., Conclusion: Infection with N gonorrhoeae and C trachomatis is commonly asymptomatic among men in this rural African population. This has important implications for the design of control programmes for sexually transmitted disease.

Purpose: The presence of nasal discharge on a child's face increases the risk of active trachoma, suggesting that Chlamydia trachomatis in nasal secretions may be a possible source of ocular reinfection. The prevalence of chlamydia in nasal secretions and the risk of reinfection after mass treatment was investigated in a hyperendemic area of Tanzania., Methods: In one village a total of 232 children aged 1 to 7 years were followed before and after mass treatment. Clinical trachoma, and microbiologic evidence of chlamydia, were assessed at baseline, 2 and 4 weeks into mass treatment, and 4 weeks after treatment stopped. The presence of chlamydia in ocular and nasal secretions was determined by polymerase chain reaction-enzyme immunoassay techniques., Results: Of the 232 children, 59% had clinical trachoma and 27% had nasal specimens positive for chlamydia. Children with positive ocular chlamydia specimens and/or clinical trachoma were significantly more likely to have positive nasal specimens. At the end of mass treatment, only 4% of children had positive ocular specimens. However, 1 month after treatment stopped, the incidence of new infection was 21%. The rate of new ocular infections in those who had negative ocular specimens after treatment was similar between those who had positive and those who had negative nasal specimens at baseline. Positive ocular specimens at baseline was not a predictor of risk of new infection after treatment (odds ratio = 1.18, 95% confidence interval = 0.58, 2.40), suggesting these new infections were not the result of latent or persistent organism., Conclusions: These data do not support a role for nasal secretions in causing reinfection after treatment. One mass topical treatment alone is unlikely to be effective in trachoma hyperendemic areas as shown by the rapid re-emergence of infection.

Objective: To evaluate the first void urine (FVU) specimen in screening for urethritis and its microbial aetiologies in a male African population in which urinary schistosomiasis is also prevalent., Patients and Methods: Two hundred and forty eight males aged 15-54 years provided FVU specimens: 55 patients from a clinic for sexually transmitted diseases (STD), 151 patients from a medical outpatient clinic and 42 villagers from an area of high endemicity for S haematobium. Specimens were tested for leucocyte esterase (LE) using a dipstick (Nephur-Test+Leuco, Boehringer-Mannheim France SA). Ova of S haematobium were sought in terminal urine samples from all subjects. For all STD patients, and all medical outpatients with a positive LE test, urine and urethral swabs were tested for Chlamydia trachomatis antigen, and urethral swabs were tested for Neisseria gonorrhoeae by gram stain and isolation., Results: The prevalence of LE positivity was 38/41 in STD patients with urethral signs or symptoms (93%), 5/14 among other STD patients (36%), 21/151 among medical outpatients (15%) and 13/42 among villagers (31%). As a screening test for urethral infection (detection of gonorrhoea or chlamydia and/or > or = 5 polymorphs per high power field on gram stain) the LE test had a sensitivity of 94% and a specificity of 53% among STD patients. Of 24 STD patients with gonococcal or chlamydial infection, 23 had a positive LE test (96%). Among general medical outpatients, 12 of 22 with a positive LE test had either conventionally defined urethritis or gonococcal or chlamydial infection, giving a positive predictive value of 55% for the LE test in this group. Of 18 subjects in all groups with urinary schistosomiasis nine had a positive LE test (50%), although three of these also had gonorrhoea. Chlamydial antigen was detected in the FVU specimen of all six subjects in whom it was detected in a urethral swab, and in an additional three subjects in the outpatient group., Conclusions: The FVU, which is an easily collected and non-invasive specimen, can provide valuable information on the prevalence of urethritis and on its microbial aetiology among the general male population in African countries.

A longitudinal study of trachoma was conducted among 100 members of nine families living in a hyperendemic area of Tanzania. Family members were examined for trachoma every three months for one year and conjunctival specimens were collected for antigen detection, which was performed either by direct fluorescent antibody cytologic analysis or enzyme immunoassay. The serovar specificity of tear antibodies was determined. Overall, young children tended to form a core of those with persistent, often severe, disease who consistently shed Chlamydia. These children are a potential source of infection in their family. Chlamydia could be identified early in the course of presumed recently acquired infections, but not later in resolving infections. This temporal change may account for the discrepancies between demonstrable organisms and clinical disease seen in cross-sectional studies. Several children were identified who did not develop trachoma despite having Chlamydia identified in conjunctival scrapings. Their ability to resist infection may offer clues for vaccine development. The study of serovar specificity is consistent with the intrafamily transmission of trachoma, but was confounded by the large family size and the potential for separate transmission units to occur within large extended families. These observations give further understanding of the natural history and kinetics of the transmission of trachoma that should be of use in developing and evaluating intervention studies.

Specimens for chlamydial isolation culture and direct fluorescent antibody cytology (DFA) were collected from 1671 women and children from a trachoma-endemic area in Central Tanzania. Trachoma was graded using the new World Health Organization grading scheme, and 54% of the children and 9% of the women had inflammatory trachoma (TF or TI). DFA, using the presence of five elementary bodies as the criterion for a positive test, had a sensitivity of 88.0% and a specificity of 87.5% compared to culture and a sensitivity of 54.7% and specificity of 92.8% compared to clinical diagnosis. Altogether, 52.9% of those with trachoma grade TF were positive on either or both culture and DFA versus 77.0% of those with TI. Twenty-nine isolates were serotyped; 18 were serovar A, ten were serovar B, and one was serovar Ba. Positive cultures or DFA were obtained in 6.9% of those graded clinically as not having TF or TI and in a smaller number of those without any perceptible evidence of disease. Conversely, organisms could not be demonstrated in a number of people with severe inflammation (TI) even though some became positive after multiple repeated culture. These two findings of infection without disease and disease without evidence of infection suggest the importance of the immunologic response to infection in determining the clinical status. DFA was found to be an appropriate test for future field studies of trachoma. Further studies of those with disease but without agent and of those with agent but without disease will help understand the dynamics of infection and transmission and the role of the immune response in this important blinding disease.