BackgroundBlinding trachoma, caused by the bacteria Chlamydia trachomatis, is a neglected tropical disease targeted for elimination by 2020. A major component of the elimination strategy is mass drug administration (MDA) with azithromycin. Currently, program decisions are made based on clinical signs of ocular infection, but we have been investigating the use of antibody responses for post-MDA surveillance. In a previous study, IgG responses were detected in children lacking clinical evidence of trachoma, suggesting that IgG responses represented historical infection. To explore the utility of serology for program evaluation, we compared IgG and IgA responses to trachoma antigens and examined changes in IgG and IgA post-drug treatment.MethodsDried blood spots and ocular swabs were collected with parental consent from 264 1–6 year olds in a single village of Kongwa District, central Tanzania. Each child also received an ocular exam for detection of clinical signs of trachoma. MDA was given, and six months later an additional blood spot was taken from these same children. Ocular swabs were analyzed for C. trachomatis DNA and antibody responses for IgA and total IgG were measured in dried bloods spots.ResultsBaseline antibody responses showed an increase in antibody levels with age. By age 6, the percentage positive for IgG (96.0%) was much higher than for IgA (74.2%). Antibody responses to trachoma antigens declined significantly six months after drug treatment for most age groups. The percentage decrease in IgA response was much greater than for IgG. However, no instances of seroreversion were observed.ConclusionsData presented here suggest that focusing on concordant antibody responses in children will provide the best serological surveillance strategy for evaluation of trachoma control programs.
BackgroundTrachoma 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.MethodologyWe 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 findingsThe 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.ConclusionsThe 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 infection with Chlamydia trachomatis can lead to trachoma, a leading infectious cause of blindness. Trachoma is targeted for elimination by 2020. Clinical grading for ocular disease is currently used for evaluating trachoma elimination programs, but serological surveillance can be a sensitive measure of disease transmission and provide a more objective testing strategy than clinical grading. We calculated the basic reproduction number from serological data in settings with high, medium, and low disease transmission based on clinical disease. The data showed a striking relationship between age seroprevalence and clinical data, demonstrating the proof-of-principle that age seroprevalence predicts transmission rates and therefore could be used as an indicator of decreased transmission of ocular trachoma.
Background Individuals who are sexually active may want to make a decision as to whether they are at risk for having a sexually transmitted infection (STI) such as Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis. Our goal was to develop and evaluate a simple self-taken sexual risk quiz for participants, ordering an online STI self-collection test kit to determine whether the score predicted infection status. Methods As part of the IWantTheKit programme for home sample self-collection for STIs, 2010–2013, the programme asked male and female users to voluntarily take a risk quiz. The six-question quiz was about risk behaviour and included an age question. Data analyses were stratified by gender as determined a priori. Scores 0–10 were stratified into risk groups for each gender based on similar risk score-specific STI prevalence. Retrospective analyses were performed to assess whether risk group predicted aggregate STI positivity. Urogenital/rectal mailed samples were tested by nucleic acid amplification tests. Results More females (N=836) than males (N=558) provided voluntary risk scores. The percentage of eligible participants who submitted scores was 43.9% for both females and males. There was a higher STI infection rate in females (14.0%) than in males (7.0%) for having any STI (p<0.001). Multivariate logistic analysis for females, which controlled for age and race, demonstrated that a higher risk score group independently predicted risk for having an STI (OR of 2.2 for risk scores 5–7 and 4.2 OR for scores of 8–10). For males, the multivariate model, which controlled for race, indicated that no risk score group was associated having an STI. Conclusions Results of a participant’s own sexual risk quiz score independently predicted STI positivity for women, but not for men. Further study of this simple risk quiz is required.
BackgroundThe World Health Organization (WHO) now requires a second surveillance survey for trachoma after an impact assessment has found follicular trachoma (TF) <5% to determine if re-emergence has occurred. Using new WHO guidelines, we undertook surveillance surveys, and determined the prevalence of infection and antibody positivity, in two districts in Nepal.Methods20 clusters were randomly selected within each district, 15 were randomly selected for antibody testing. In each cluster, we randomly selected 50 children ages 1–9 years and 100 adults ≥15 years. TF and trachomatous trichiasis (TT) were evaluated. Conjunctival swabs to test for chlamydial infection using GenXpert platform were obtained, and dried blood spots were collected to test for antibodies to Chlamydia Trachomatis pgp3 using the Luminex platform.Findings3 cases of TF were found in the two districts, and one case of infection. Pgp3 antibody positivity was 2·4% (95% confidence interval: 1·4%, 3·7%), and did not increase with age (P = 0.24). No clustering of antibody positivity within communities was found. TT prevalence was <1/1,000 population.InterpretationThe surveillance surveys, as proposed by WHO, showed no evidence for re-emergence of trachoma in two districts of Nepal. The low level and no significant increase by age in seroprevalence of antibodies to C trachomatis pgp3 antigen deserve further investigation as a marker of interruption of transmission.
Background Self-obtained penile-meatal swabs and urine specimens have been used for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) for outreach screening in men. Objective To compare the sensitivity of self-collected male penile-meatal swabs and urine for the detection of CT, NG and TV. Methods Matching penile-meatal swabs and urines were collected at home after recruitment to the study; via the internet programme, http://www.iwantthekit.org. The instructions directed the participant to place the tip of a Copan flocked swab at the meatal opening of the urethra to collect the penile-meatal sample. Two ml of urine was collected after the swab onto a Copan sponge-on-a-shaft collection device. Both swab and urine were placed into individual Aptima transport media tubes and mailed to the laboratory for testing. All specimens were tested for CT and NG using the GenProbe Aptima Combo2 Assay and for TV using GenProbe Aptima Analyte Specific Reagents with TV oligonucleotides. Results Of 634 men, 86 (13.6%) were positive for CT, 9 (1.4%) were positive for NG and 56 (9.3%) positive for TV. For CT, swab sensitivity was 81/86 (94.2%), and urine sensitivity was 66/86 (76.7%). For NG, swab sensitivity was 9/9 (100%) and urine sensitivity was 8/9 (88.9%). For TV, swab sensitivity was 45/56 (80.4%) and urine sensitivity was 22/56 (39.3%). Conclusions Self-obtained penile-meatal swabs provided for the detection of more CT, NG and TV, than urine specimens.
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. The leading infectious cause of preventable blindness worldwide is trachoma, which occurs in resource-limited countries, including sub-Saharan Africa, and is caused by repetitive and untreated ocular Chlamydia trachomatis infections (1, 2, 3). The current reservoir of active disease and infection is in children; in villages where such infections are hyperendemic, C. trachomatis infections have been found in children who have been treated at least once though mass drug administration (MDA) (1, 4). PCR is considered to be the current gold standard test, although there is no defined gold standard test for ocular C. trachomatis infections (5, 6). The Roche Amplicor CT PCR assay (Roche Diagnostics, Indianapolis, IN) has been used in major trials to monitor infection following MDA (7). Testing for C. trachomatis infection is often difficult in regions associated with trachoma; the laboratory infrastructure is often deficient or nonexistent, and there is often a lack of trained personnel, equipment, funding, and cleanliness of testing areas. The Cepheid GeneXpert CT/NG Research Use Only (RUO) assay (GeneXpert) (Cepheid Inc., Sunnyvale, CA) is a rapid test designed to produce results relatively quickly, with little hands-on time required, and could be useful in areas where trachoma occurs. We evaluated the Abbott m2000 RealTime CT (m2000) assay (Abbott Molecular Diagnostics, Des Plaines, IL) for detection of C. trachomatis in ocular specimens from Tanzania as a means to reduce turnaround time for results and increase sample throughput. A first-generation GeneXpert CT/NG assay (GeneXpert) was subsequently evaluated as a potential method for testing ocular specimens in the field to expedite provision of immediate treatment of C. trachomatis ocular infections, pending demonstration of its performance in a laboratory setting.Duplicate ocular swab specimens (n ϭ 304) from the same eye were collected from children in Tanzania for the detection of C. trachomatis infection; collection was performed as previously described (8). Samples were shipped frozen in a dry state to the Johns Hopkins University (JHU) Research Laboratory in Baltimore, MD, and stored at Ϫ80°C until testing. Swabs were rehydrated with 1 ml of sterile molecular analysis-grade diethylpyrocarbonate (DEPC) water (Quality Biological, Inc., Gaithersburg, MD). One set of the duplicate specimens was tested by Amplicor (Roche Diagnostics) and GeneXpert (Cepheid) and, for discordance testing, by the GenProbe-Aptima CT (ACT) assay (Gen-Probe Hologi...
A serologic test for antibodies to chlamydial antigen pgp3 may be a useful tool for trachoma surveillance. However, little is known about the stability of antibody status over time, or factors associated with seroreversion/conversion. A cohort of 2,111 children ages 1–9 years in Tanzania were followed for one year in the absence of mass azithromycin. At baseline and follow-up, they were evaluated for trachoma, chlamydial infection, and antibodies to chlamydial antigen pgp3. At baseline, 31% of children were seropositive for pgp3 antibodies and 6.4% seroreverted to negative over one year. Of those seronegative, 9.8% seroconverted over the year. The seroreverters had lower baseline mean fluorescence intensity (MFI-BG) values compared to the seropositives who remained positive (Odds Ratio = 0.04 for every unit increase in log10MFI-BG, 95% CI = 0.02–0.09), and were more likely to live in communities with trachoma <5% (p < 0.008). While seroconversion was expected, seroreversion was unexpected. The low seroprevalence rate reported from low endemic areas may be due to seroreversion as well as lack of exposure.
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