PubMed Health⌕ Search

Biomedical subjects

Thomas M Lietman

Publications and source records attributed to Thomas M Lietman.

16 recordsLinked to original sources

Comparison of an rRNA-based and DNA-based nucleic acid amplification test for the detection of Chlamydia trachomatis in trachoma.

BACKGROUND/AIM: The World Health Organisation (WHO) hopes to achieve global elimination of trachoma, still the leading cause of preventable blindness worldwide, in part through mass antibiotic treatment. DNA-based nucleic acid amplification tests (NAATs) are currently used to evaluate the success of treatment programmes by measuring the prevalence of C trachomatis infection. Some believe that newer ribosomal RNA (rRNA)-based tests may be much more sensitive since bacterial rRNA is present in amounts up to 10 000 times that of genomic DNA. Others believe that rRNA-based tests are instead less sensitive but more specific, due to the presence of dead or subviable organisms that the test may not detect. This study compares an rRNA-based test to a DNA-based test for the detection of ocular C trachomatis infection in children living in trachoma-endemic villages. METHODS: An rRNA-based amplification test and DNA-based polymerase chain reaction (PCR) were performed on swab specimens taken from the right upper tarsal conjunctiva of 56 children aged 0-10 years living in two villages in Amhara, Ethiopia. RESULTS: The rRNA-based test detected ocular C trachomatis infection in 35 (63%) subjects compared with 22 (39%) detected by PCR (McNemar's test, p = 0.0002). The rRNA-based test gave positive results for all subjects that were positive by PCR, and also detected infection in 13 (23%) additional subjects. CONCLUSION: The rRNA-based test appears to have significantly greater sensitivity than PCR for the detection of ocular chlamydial infection in children in trachoma-endemic villages. Using the rRNA-based test, we may be able to detect infection that was previously missed with PCR. Past studies using DNA-based tests to assess prevalence of infectious trachoma following antibiotic treatment may have underestimated the true prevalence of infection.

Child↗

Effect of a single mass antibiotic distribution on the prevalence of infectious trachoma.

CONTEXT: The World Health Organization recommends mass antibiotic distributions in its strategy to eliminate blinding trachoma as a public health concern. Some hypothesize that a single distribution is sufficient to control the ocular strains of chlamydia that cause trachoma. Others believe infection will inevitably return and periodic treatments or other measures are essential. OBJECTIVE: To determine whether ocular chlamydial infection returns to the community up to 24 months after a single mass antibiotic distribution in a hyperendemic region of Ethiopia. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal cohort study conducted March 2003 to March 2005 in the Gurage Zone of Ethiopia. Eight randomly selected villages were assessed for ocular chlamydial infection. Fifteen untreated villages were randomly chosen at 12 months to allow assessment of a secular trend. INTERVENTION: A single dose of oral azithromycin was offered to all residents of the 8 selected villages who were aged 1 year or older. MAIN OUTCOME MEASURE: Prevalence of ocular chlamydial infection in all children aged 1 to 5 years from each intervention village prior to treatment and 2, 6, 12, 18, and 24 months after mass antibiotic treatment, and also in untreated villages enrolled at 12 months. RESULTS: Five hundred fifteen children were examined for ocular chlamydial infection at baseline. For the follow-up examinations, the mean participation rate was 83%. The mean prevalence of infection in children aged 1 to 5 years decreased from 43.5% (95% confidence interval [CI], 35.0%-52.0%) to 5.1% (95% CI, 1.1%-9.2%) after treatment. On average, infection returned gradually over 24 months to 11.3% (95% CI, 4.5%-18.1%; P = .001). In 7 of 8 villages, infection was higher at 24 months than at 2 months. In the remaining village, no infection could be identified at any point after treatment. Villages enrolled at 12 months had significantly fewer infections than those enrolled 12 months earlier, suggesting a secular trend (P<.001). CONCLUSIONS: Ocular chlamydial infection was not eliminated in children aged 1 to 5 years after a single mass azithromycin distribution; it slowly returned over 24 months, although not to baseline levels. Repeated treatments or other effective measures will be necessary for elimination.

Anti-Bacterial Agents↗

Atopic disease and herpes simplex eye disease: a population-based case-control study.

PURPOSE: To determine whether atopy is associated with herpes simplex virus (HSV) ocular disease. DESIGN: Retrospective, population-based, case-control study. METHODS SETTING: Large, regional health maintenance organization (Northern California Kaiser Permanente). STUDY POPULATION: 1,042,351 people over a one-year period. OBSERVATION PROCEDURES: Electronic database search for HSV ocular disease and subsequent chart review determined study eligibility. Two age-matched control groups (one population-based and one clinic-based) were randomly chosen. Medical record review determined the presence of atopy. Severe atopic disease was defined by diagnostic code or illness requiring an emergency room visit, hospitalization, or treatment with a systemic corticosteroid. MAIN OUTCOME MEASURES: Presence of HSV eye disease, presence of atopy, and characterization of atopy severity. RESULTS: HSV eye disease was found in 172 patients. HSV cases had a greater prevalence of atopy (34%, 58/172) than the clinic-based (25%, 43/172) or the population-based controls (21%, 36/172, odds ratio (OR) 1.5, 95% confidence interval (CI) 0.9 to 2.6 and OR 1.9, 95%, CI 1.1 to 3.3, respectively). The association of HSV ocular disease with severe atopy was even greater, with a history of severe atopic disease in 13% (22/172) of patients with HSV ocular disease as compared with 6% (11/172) of patients in the clinic control group and 3% (5/172) of patients in the population control group (OR 2.0, 95% CI 0.7 to 5.9 and OR 4.8, 95% CI 1.6 to 19.2, respectively). CONCLUSIONS: Patients with HSV ocular disease are more likely to have a history of atopic disease, especially severe atopic disease, than age-matched controls.

Case-Control Studies↗

Antioxidants in prevention of cataracts in South India: methodology and baseline data*.

PURPOSE: To describe the methodology and baseline data for the Antioxidants in Prevention of Cataracts (APC) study in South India. METHODS: The APC study is a prospective, 5-year, randomized, triple-masked, placebo-controlled, field-based clinical trial to examine the effect of antioxidants (combination tablet of vitamins A, C, and E) on progression of cataract. The primary outcome variable is cataract progression (nuclear opalescence), evaluated with the slit-lamp biomicroscope by the Lens Opacification Classification System III method. Secondary outcome variables are progression in cortical and posterior subcapsular opacity and nuclear color, change in best corrected visual acuity, myopic shift, and treatment failure (progression to cataract surgery or best corrected vision worse than 20/400 in an eye). Inclusion criteria are age between 35 and 50 years and best-corrected visual acuity of 20/40 or better. Exclusion criteria are a diagnosis of diabetes mellitus or nonfasting blood glucose level>7.8 mmol/L, history or presence of various ocular conditions or treatment forms, or current use of vitamin supplements. Baseline ophthalmic, demographic, and potential cataract risk factor data (such as smoking, sunlight, or alcohol exposure) were compared between groups on an intent-to-treat basis. RESULTS: Of 954 people screened, 798 were enrolled, a sample size which exceeded the required estimate. More than 80% of subjects had 20/20 or better vision in at least one eye, and baseline prevalence of significant cataract according to the LOCS III grading scale was high. The two treatment groups were comparable for all baseline measures except alcohol intake. CONCLUSION: The sample size and group baseline characteristics will provide sufficient power to detect a change in cataract progression within 5 years.

Adult↗

Genetically diverse group A streptococci from children in far-western Nepal share high genetic relatedness with isolates from other countries.

The genetic diversity of group A streptococci (GAS) throughout much of the world has not been adequately explored. To assess genetic variation among GAS in western Nepal, 120 noninvasive GAS, collected from eight different villages, were genetically characterized using emm typing, sof sequencing, and multilocus sequence typing (MLST). A high level of genetic diversity was observed among these isolates, with 51 genotypes based upon 51 multilocus sequence types (STs), 45 emm sequence types, and 28 sof sequence types. On the basis of shared ST-emm and sof-emm associations, 40 of the 51 genotypes were identical or highly related to genotypes characterized from locations outside of Nepal, even though most of the emm sequence and clonal types are rare among GAS within the United States. When analyzing all known STs highly related to Nepal STs, only one example of similar STs shared between a sof PCR-positive strain and a sof PCR-negative strain was observed. Since previous data indicate free exchange of MLST loci between sof-positive and sof-negative strains, there is possibly selection against the expansion of subclones resulting from horizontal transfers of sof or emm genes between sof-positive and sof-negative strains. All 45 emm types encountered in Nepal have also been documented from other countries. These data, together with data encompassing the past decade of emm type surveillance, support the possibility that most existing GAS emm types have been discovered. Similarly, since most (40/51) strain types were highly related to strains found elsewhere, it is likely that a major fraction of the existing GAS clonal complexes have been discovered.

Antigens, Bacterial↗

Seasonal effects in the elimination of trachoma.

The World Health Organization currently recommends annual mass antibiotic treatment to eliminate the ocular chlamydia that cause blinding trachoma. Active trachoma is believed to be seasonal in many areas of the world, and the optimal season in which to treat has not as yet been established. Here we use mathematical models of disease transmission to demonstrate that ideally, treatment should be administered before the low season to have the greatest chance of locally eliminating infection.

Humans↗

Mass antibiotic treatment and community protection in trachoma control programs.

Azithromycin is highly effective against trachoma, but the practical difficulties of community-wide distribution often leave many individuals untreated. We demonstrate, after mass azithromycin treatment of a population in Ethiopia, an indirect protective effect that occurred among untreated children who resided in villages in which most individuals had been treated. Similarities with the indirect protection within a treated community (i.e., "herd protection") that has been observed in vaccination programs are discussed.

Anti-Bacterial Agents↗

Feasibility of eliminating ocular Chlamydia trachomatis with repeat mass antibiotic treatments.

CONTEXT: Mass antibiotic administrations for ocular chlamydial infection play a key role in the World Health Organization's trachoma control program. Mathematical models suggest that it is possible to eliminate trachoma locally with repeat mass treatment, depending on the coverage level of the population, frequency of mass treatments, and rate that infection returns into a community after each mass treatment. Precise estimates of this latter parameter have never been reported. OBJECTIVE: To determine the rate at which chlamydial infection returns to a population after mass treatment and to estimate the treatment frequency required for elimination of ocular chlamydia from a community. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal cohort study of 24 randomly selected villages from the Gurage Zone in Ethiopia conducted February 2003 to October 2003. A total of 1332 children aged 1 to 5 years were monitored for prevalence of ocular chlamydial infection pretreatment and 2 and 6 months posttreatment. INTERVENTIONS: All individuals older than 1 year were eligible for single-dose oral azithromycin treatment. Pregnant women were offered tetracycline eye ointment. MAIN OUTCOME MEASURES: Prevalence of ocular chlamydial infection, measured by polymerase chain reaction, in children aged 1 to 5 years, in each of 24 villages at each time point was used to estimate the rate of return of infection and the treatment frequency necessary for elimination. RESULTS: The prevalence of infection was 56.3% pretreatment (95% confidence interval [CI], 47.5%-65.1%), 6.7% 2 months posttreatment (95% CI, 4.2%-9.2%), and 11.0% 6 months posttreatment (95% CI, 7.3%-14.7%). Infection returned after treatment at an exponential rate of 12.3% per month (95% CI, 4.6%-19.9% per month). The minimum treatment frequency necessary for elimination was calculated to be once every 11.6 months (95% CI, 7.2-30.9 months), given a coverage level of 80%. Thus, biannual treatment, already being performed in some areas, was estimated to be more than frequent enough to eventually eliminate infection. CONCLUSION: The rate at which ocular chlamydial infection returns to a community after mass treatment suggests that elimination of infection in a hyperendemic area is feasible with biannual mass antibiotic administrations and attainable coverage levels.

Anti-Bacterial Agents↗

Trachoma decline and widespread use of antimicrobial drugs.

Trachoma is disappearing in many parts of the world, even in the absence of specific control programs. Following mass antimicrobial drug treatments for trachoma in western Nepal, the prevalence of trachoma declined far more rapidly than could be attributed to the control program alone. Pharmacy surveys in the same region found that children received more antichlamydial drugs from sources outside the trachoma program than they did from the program itself. We demonstrate that high background antimicrobial drug use may be responsible for much of the observed decline in trachoma and discuss its potential role in eliminating this infectious disease.

Anti-Bacterial Agents↗

Does the diagnosis of trachoma adequately identify ocular chlamydial infection in trachoma-endemic areas?

We evaluated the validity of clinically determined active trachoma as a surrogate for chlamydial eye infection in 1059 children from the Egyptian arm of the Azithromycin in the Control of Trachoma study. Participants were determined to be "clinically active" if they had >or=5 follicles or intense inflammatory infiltration on the tarsal conjunctiva. Conjunctival swabs were tested using ligase chain reaction (LCR) to detect chlamydial DNA. Of clinically active children aged 1-10 years, 31% did not have infection, as determined by LCR. Conversely, 31% of infected children were not clinically active; 78% of clinically active children aged 1-5 years were infected, versus 17% of those aged 11-15 years. The proportion of clinically active children who were infected decreased from 67% before treatment to 10% 14 months after mass azithromycin treatment. Clinically active trachoma is not always a reliable marker of infection, particularly in teenagers and after treatment.

Adolescent↗

Pattern of antibiotic use in a trachoma-endemic region of Nepal: implications for mass azithromycin distribution.

PURPOSE: To investigate antibiotic utilization in a rural district of western Nepal that is currently receiving azithromycin as part of a trachoma program and is being monitored by the Centers for Disease Control and Prevention (CDC) for drug resistance. METHODS: Antibiotic purchase receipts were collected for 3 months from all medicine halls, pharmacies, and government sub-health posts in a sub-district of Western Nepal. Supplementary surveys of antibiotic sales were performed in different seasons. RESULTS: Macrolides account for 3.9% of total antibiotic use, far less than quinolones, penicillins, tetracyclines, and sulfonamides. CONCLUSIONS: If trachoma programs in Western Nepal generate transient macrolide resistance in pneumococcus and other bacteria, the epidemiological impact may not be great, as macrolides are not commonly used in the area.

Anti-Bacterial Agents↗

Efficacy of transport media use versus direct inoculation of blood agar plates in the microbiologic evaluation of experimental Streptococcus pneumoniae keratitis.

PURPOSE: To compare the microbiologic yield of cultures obtained by direct inoculation of blood agar plates (BAP) from corneal ulcer swabbings versus indirect inoculation via transport media in a rabbit model of Streptococcus pneumoniae bacterial keratitis. METHODS: The corneas of 12 rabbits were inoculated with S. pneumoniae. Keratitis was confirmed 18 hours later. Sampling was performed at four 2.5-hour intervals. At each interval, corneal swabs were directly applied to BAP and placed into transport medium: thioglycollate and Amies medium without charcoal. Swabbings were then subcultured onto BAP at two time points: 2 and 24 hours after collection in transport medium. Plates were evaluated 48 hours later. Organism recovery rates were measured in terms of the number of positive culture plates observed and the bacterial colony counts on each plate. RESULTS: The rate of positive cultures overall was 69%. The recovery rates were similar for direct inoculation, inoculation via Amies held for 2 hours, and inoculation via Amies held for 24 hours. Direct inoculation yielded fewer colonies than indirect inoculation via Amies held for 24 hours (p = 0.008). Direct inoculation yielded a higher rate of positive cultures than did thioglycollate held for 2 hours (p = 0.004) or 24 hours (p < 0.001). The rate of nonpneumococcal contaminants ranged from 6% of BAP subcultured from thioglycollate held for 24 hours to 28% of directly inoculated BAP. CONCLUSIONS: Amies medium without charcoal may be used as a transport medium for up to 24 hours in the recovery of S. pneumoniae from corneal ulcers in this rabbit model. Thioglycollate appears to be less effective as a transport medium. Results of this study may justify studies of other transport media and/or other corneal pathogens. Altogether, such studies may provide justification for human clinical trials.

Agar↗