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1.
Lancet ; 379(9811): 143-51, 2012 Jan 14.
Article in English | MEDLINE | ID: mdl-22192488

ABSTRACT

BACKGROUND: In trachoma control programmes, azithromycin is distributed to treat the strains of chlamydia that cause ocular disease. We aimed to compare the effect of annual versus twice-yearly distribution of azithromycin on infection with these strains. METHODS: We did a cluster-randomised trial in 24 subdistricts in northern Ethiopia, which we randomly assigned to receive annual or twice-yearly treatment for all residents of all ages. Random assignment was done with the RANDOM and SORT functions of Microsoft Excel. All individuals were offered their assigned treatment of a single, directly observed, oral dose of azithromycin. A 6 week course of topical 1% tetracycline ointment, applied twice daily to both eyes but not directly observed, was offered as an alternative to azithromycin in patients younger than 12 months, and in patients with self-reported pregnancy, with allergy, or who refused azithromycin. Our primary, prespecified outcome was the prevalence of ocular chlamydial infection in a random sample of children aged 0-9 years at baseline and every 6 months for a total of 42 months within sentinel villages. Our analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00322972. FINDINGS: Antibiotic coverage of children aged 1-9 years was greater than 80% (range 80·9 to 93·0) at all study visits. In the groups treated annually, the prevalence of infection in children aged 0-9 years was reduced from a mean 41·9% (95% CI 31·5 to 52·2) at baseline to 1·9% (0·3 to 3·5) at 42 months. In the groups treated twice yearly, the prevalence of infection was reduced from a mean 38·3% (29·0 to 47·6) at baseline to 3·2 % (0·0 to 6·5) at 42 months. The prevalence of ocular chlamydial infection in children aged 0-9 years in groups treated annually was not different from that of the groups treated twice yearly at 18, 30, and 42 months (pooled regression p>0·99, 95 % CI -0·06 to 0·06). The mean elimination time in the twice-yearly treatment group was 7·5 months earlier (2·3 to 17·3) than that of the annual group (p=0·10, Cox proportional hazards model). INTERPRETATION: After 42 months of treatment, the prevalence of ocular infection with chlamydia was similar in the groups treated annually and twice yearly. However, elimination of infection might have been more rapid in the groups of villages that received treatment twice yearly. FUNDING: National Institutes of Health (NEI U10 EY016214).


Subject(s)
Anti-Bacterial Agents/administration & dosage , Azithromycin/administration & dosage , Trachoma/drug therapy , Child , Child, Preschool , Directly Observed Therapy , Endemic Diseases , Ethiopia/epidemiology , Female , Humans , Hypersensitivity/complications , Infant , Infant, Newborn , Intention to Treat Analysis , Ointments , Pregnancy , Pregnancy Complications/drug therapy , Tetracycline/administration & dosage
2.
PLoS Negl Trop Dis ; 5(12): e1441, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22180804

ABSTRACT

BACKGROUND: An important component of the World Health Organization's comprehensive trachoma elimination strategy is the provision of repeated annual mass azithromycin distributions, which are directed at reducing the burden of ocular chlamydia. Knowledge of characteristics associated with infection after mass antibiotic treatments could allow trachoma programs to focus resources to those most likely to be infected with ocular chlamydia. METHODOLOGY/PRINCIPAL FINDINGS: We monitored 12 communities in rural Ethiopia that had received 3 annual mass azithromycin treatments as part of a cluster-randomized trial for trachoma. One year after the third treatment, a random sample of children from each village received conjunctival examination for follicular trachomatous inflammation (TF) and intense trachomatous inflammation (TI), conjunctival swabbing for chlamydial RNA and DNA, and a household survey. The primary outcome for this study was RNA evidence of ocular chlamydia, which we detected in 41 of 573 swabbed children (7.2%, 95%CI 2.7-17.8). In multivariate mixed effects logistic regression models, ocular chlamydial RNA was significantly associated with ocular discharge (OR 2.82, 95%CI 1.07-7.42), missing the most recent mass azithromycin treatment (OR 2.49, 95%CI 1.02-6.05), having a sibling with ocular chlamydia (OR 4.44, 95%CI 1.60-12.29), and above-median community population (OR 7.81, 95%CI 1.56-39.09). Ocular chlamydial infection was also independently associated with TF (OR 3.42, 95%CI 1.56-7.49) and TI (OR 5.39, 95%CI 2.43-11.98). CONCLUSIONS/SIGNIFICANCE: In areas with highly prevalent trachoma treated with multiple rounds of mass azithromycin, trachoma programs could consider continuing mass azithromycin treatments in households that have missed prior mass antibiotic treatments, in households with clinically active trachoma, and in larger communities.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Azithromycin/administration & dosage , Trachoma/drug therapy , Trachoma/epidemiology , Child , Child, Preschool , Chlamydia trachomatis/genetics , Chlamydia trachomatis/isolation & purification , Cross-Sectional Studies , DNA, Bacterial/analysis , Ethiopia/epidemiology , Family Characteristics , Female , Humans , Logistic Models , Male , Odds Ratio , RNA, Bacterial/analysis , Risk Factors , Socioeconomic Factors , Travel
3.
Am J Trop Med Hyg ; 85(3): 518-23, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21896815

ABSTRACT

Trachoma control strategies, including latrine construction and antibiotic distribution, are directed at reducing ocular chlamydia, but may have additional benefits. In a cluster-randomized clinical trial, 24 subkebeles (administrative geographic units) in Ethiopia were offered a single mass azithromycin treatment, and half were randomized to receive an intensive latrine promotion. At a follow-up census 26 months after the baseline treatment, 320 persons had died. The mortality rate of children 1-5 years of age was 3.87 (95% confidence interval [CI] = 2.19-6.82) per 1,000 person-years in the latrine promotion arm, and 2.72 (95% CI = 1.37-5.42) per 1,000 person-years in the control arm. In a multi-level mixed effects logistic regression model controlling for age, there was no difference in mortality in persons randomized into the latrine or control arms (odds ratio = 1.18, 95% CI = 0.89-1.58). Latrine promotion provided no additional effect on mortality in the context of an azithromycin distribution program (clinicaltrials.gov, #NCT00322972).


Subject(s)
Toilet Facilities , Trachoma/mortality , Trachoma/prevention & control , Adolescent , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacology , Azithromycin/administration & dosage , Azithromycin/pharmacology , Child , Child, Preschool , Cluster Analysis , Ethiopia/epidemiology , Female , Humans , Infant , Male , Odds Ratio , Trachoma/epidemiology , Young Adult
4.
Am J Trop Med Hyg ; 85(2): 291-4, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21813850

ABSTRACT

During a cluster-randomized clinical trial for trachoma in Ethiopia, two rounds of adverse event surveillance were performed in a random sample of communities after community-wide mass azithromycin treatment. The prevalence of any reported adverse event ranged from 4.9% to 7.0% in children 1-9 years of age and from 17.0% to 18.7% in persons ≥ 10 years of age. Adverse events appeared to cluster by household and perhaps by village. Mass azithromycin distributions were well tolerated in this setting.


Subject(s)
Azithromycin/adverse effects , Azithromycin/therapeutic use , Gastrointestinal Diseases/chemically induced , Trachoma/prevention & control , Antibiotic Prophylaxis , Azithromycin/administration & dosage , Child , Child, Preschool , Cluster Analysis , Ethiopia/epidemiology , Female , Humans , Infant , Male
5.
Int Health ; 3(2): 75-84, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21785663

ABSTRACT

The World Health Organization (WHO) recommends environmental improvements such as latrine construction in the integrated trachoma control strategy, SAFE. We report a cluster-randomized trial assessing the effect of intensive latrine promotion on emergence of infection with ocular Chlamydia trachomatis after mass treatment with antibiotics.Twenty-four communities in Goncha Seso Enesie woreda, Amhara Regional State, Ethiopia, were enumerated, and a random selection of 60 children aged 0- 9 years in each was monitored for clinical signs of trachoma and ocular chlamydial infection at baseline, 12 and 24 months. All community members were offered treatment with a single dose of oral azithromycin or topical tetracycline. After treatment, 12 subkebeles were randomized to receive intensive latrine promotion. Mean cluster ocular infection in the latrine and the non-latrine arms were reduced from 45.5% (95% CI 34.1-56.8%) and 43.0% (95% CI 31.1-54.8%) respectively at baseline to 14.6% (95% CI 7.4-21.8%) and 14.8% (95% CI 8.9-20.8%) respectively at 24 months (P=0.93). Clinical signs fell from 72.0% (95% CI 58.2-85.5%) and 61.3% (95% CI 44.0-78.5%) at baseline to 45.8% (36.0-55.6%) and 48.5% (34.0-62.9%) respectively at 24 months (P=0.69). At 24 months, estimated household latrine coverage and use were 80.8% and 61.7% respectively where there had been intensive latrine promotion and 30.0% and 25.0% respectively in the single treatment only arm. We were unable to detect a difference in the prevalence of ocular chlamydial infection in children due to latrine construction.

7.
Clin Infect Dis ; 52(7): 883-8, 2011 Apr 01.
Article in English | MEDLINE | ID: mdl-21427395

ABSTRACT

BACKGROUND: Mass azithromycin distributions are used to clear ocular strains of chlamydia that cause trachoma, but treatments may also affect respiratory infections, diarrhea, and malaria. Here, we monitor a large cohort in which almost 90% of individuals received azithromycin. We assess whether receiving treatment is associated with reduced all-cause and infectious childhood mortality. METHODS: As part of a clinical trial for trachoma, a census was conducted in 24 communities in rural Ethiopia. All individuals ≥1 year of age were eligible for single-dose oral azithromycin, although antibiotic coverage was not universal. A follow-up census was performed 26 months after treatment to estimate all-cause mortality among children 1-5 years of age, and verbal autopsies were performed to identify infectious mortality. RESULTS: The cohort included 35,052 individuals ≥1 year of age and 5507 children 1-5 years of age, of whom 4914 received a dose of azithromycin. All-cause mortality was significantly lower among those 1-5-year-old children who received azithromycin (odds ratio [OR]=0.35 [95% confidence interval {CI}, 0.17-0.74]), as was infectious mortality (OR=0.20 [95% CI, 0.07-0.58]). When individuals were compared only with members of the same household, azithromycin treatment was still associated with reduced all-cause mortality in children 1-5 years of age (OR=0.40 [95% CI, 0.16-0.96]), although this relationship was not statistically significant for infectious mortality (OR=0.35 [95% CI, 0.10-1.28]). CONCLUSIONS: This study demonstrated an association between mass oral azithromycin treatment and reduced all-cause and infectious childhood mortality. This relationship could not be attributed to bias at the level of the household. Mass azithromycin distributions may have benefits unrelated to trachoma.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Azithromycin/administration & dosage , Child Mortality/trends , Infant Mortality/trends , Trachoma/drug therapy , Child , Child, Preschool , Cohort Studies , Ethiopia , Female , Follow-Up Studies , Humans , Infant , Male , Rural Population
8.
Clin Infect Dis ; 51(5): 571-4, 2010 Sep 01.
Article in English | MEDLINE | ID: mdl-20649409

ABSTRACT

After 6 biannual mass distributions of oral azithromycin for trachoma in Ethiopian communities, 76.8% (95% confidence interval [CI], 66.3%-85.1%) of nasopharyngeal Streptococcus pneumoniae isolates from children aged 1-5 years were resistant to macrolides. Twelve and 24 months after the last azithromycin treatment, resistance decreased to 30.6% (95% CI, 18.8%-40.4%; P <.001 ) and 20.8% (95% CI, 12.7%-30.7%; P < .001), respectively. Macrolide resistance decreases after antibiotic pressure is removed.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Pneumococcal Infections/microbiology , Streptococcus pneumoniae/drug effects , Trachoma/prevention & control , Child, Preschool , Ethiopia/epidemiology , Female , Humans , Infant , Male , Pneumococcal Infections/drug therapy , Pneumococcal Infections/epidemiology , Trachoma/epidemiology , Trachoma/microbiology
9.
Am J Trop Med Hyg ; 82(3): 482-7, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20207878

ABSTRACT

It is unclear how the prevalence of clinically active trachoma correlates with the prevalence of ocular chlamydial infection at the community level. In 24 villages from a cluster-randomized clinical trial of mass azithromycin distributions in Ethiopia, the correlation between the prevalence of clinical activity (on examination) and chlamydial infection (by polymerase chain reaction) was moderately strong before mass antibiotic treatments (Pearson's correlation coefficient r = 0.75, 95% confidence interval [CI] = 0.52-0.87), but decreased at each time point during four biannual treatments (at 24 months, r = 0.15, 95% CI = -0.14-0.41). One year after the final treatment, the correlation coefficient had increased, but not to the pre-treatment level (r = 0.55, 95% CI = 0.30-0.73). In a region with hyperendemic trachoma, conjunctival examination was a useful indicator of the prevalence of chlamydial infection before treatments, less useful during mass treatments, but regained utility by one year after treatments had stopped.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Polymerase Chain Reaction , Trachoma/drug therapy , Trachoma/prevention & control , Adolescent , Adult , Child , Child, Preschool , Ethiopia/epidemiology , Female , Humans , Infant , Male , Prevalence , Trachoma/epidemiology , Young Adult
10.
Ophthalmic Epidemiol ; 17(2): 113-7, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20302432

ABSTRACT

PURPOSE: Trachoma is the leading infectious cause of blindness. The World Health Organization has set a goal of reducing the trachoma disease burden to a level where it is no longer a public health concern by the year 2020. Some investigators feel that local elimination of ocular chlamydia infection is possible, but little has been done to study the likelihood of reintroduction of infection from neighboring areas. Mass administration of azithromycin has been shown to dramatically reduce the prevalence of infection in many villages in central Ethiopia. However, after treatment is discontinued, infection returns. Reintroduction of infection could occur from the few remaining infected cases in a treated community or from outside the community. People traveling between villages might be responsible thus complicating the elimination of trachoma. METHODS: We conducted a survey to assess the travel pattern of the Gurage zone residents in Ethiopia. Seven hundred and seventeen households with at least one child aged 1-5 years in 48 villages were surveyed to collect the details of travel in 1 month prior to the survey. RESULTS: Seventy-eight percent of the surveyed households had at least one traveler, with the majority being women. Pre-school children, the main reservoir of clinically active infection, rarely traveled. Most travel was to the market or to school, and most for less than 1 day. CONCLUSIONS: Travel routinely takes place in these villages. Trachoma control programs in this area might consider treating areas with the same markets and schools in the same period to increase the efficacy of mass treatment.


Subject(s)
Chlamydia trachomatis/physiology , Trachoma/prevention & control , Trachoma/transmission , Travel/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Child , Child, Preschool , Ethiopia/epidemiology , Female , Humans , Infant , Male , Middle Aged , Rural Population/statistics & numerical data , Surveys and Questionnaires , Trachoma/drug therapy , Young Adult
11.
JAMA ; 302(9): 962-8, 2009 Sep 02.
Article in English | MEDLINE | ID: mdl-19724043

ABSTRACT

CONTEXT: Mass oral azithromycin distribution to affected communities is a cornerstone of the World Health Organization's trachoma elimination program. Antibiotics are provided to target the ocular strains of chlamydia that cause trachoma, but may also be efficacious against respiratory disease, diarrhea, and malaria--frequent causes of childhood mortality in trachoma-endemic areas. OBJECTIVE: To compare mortality rates of participants aged 1 to 9 years in treated communities with those in untreated communities. DESIGN, SETTING, AND PARTICIPANTS: We conducted a cluster-randomized clinical trial of mass azithromycin administration for trachoma control. Forty-eight communities (known as subkebeles) were randomized into 1 of 3 treatment schedules (annual treatment of all residents [15,902 participants], biannual treatment of all residents [17,288 participants], or quarterly treatment of children only [14,716 participants]) or into 1 group for which treatment was delayed by 1 year (control, 18,498 participants). Twelve subkebeles were randomized to each of the 4 schedules with all children in each of the 3 communities being eligible for treatment. The trial was conducted in a field setting in rural Ethiopia, May 2006 to May 2007. INTERVENTIONS: A single dose of oral azithromycin (adults, 1 g; children, 20 mg/kg) was administered for treatment of ocular Chlamydia trachomatis infection. Antibiotic coverage levels for children aged 1 to 9 years exceeded 80% at all visits. MAIN OUTCOME MEASURE: The main outcome measure was the community-specific mortality risk for children aged 1 to 9 years over the course of 1 year. Mortality was measured by enumerative census at baseline and again after 1 year. Comparison of the risk of mortality was a prespecified outcome for the clinical trial. RESULTS: The odds ratio for childhood mortality in the intervention communities was 0.51 (95% confidence interval, 0.29-0.90; P = .02; clustered logistic regression) compared with the control group. In the treated communities, the estimated overall mortality rate during this period for children aged 1 to 9 years in the untreated group was 8.3 per 1000 person-years (95% confidence interval, 5.3-13.1), while among the treated communities, the estimated overall mortality rate was 4.1 per 1000 person-years (95% confidence interval, 3.0-5.7) for children aged 1 to 9 years. CONCLUSION: In a trachoma-endemic area, mass distribution of oral azithromycin was associated with reduced mortality in children. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00322972.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Azithromycin/therapeutic use , Trachoma/prevention & control , Anti-Bacterial Agents/administration & dosage , Azithromycin/administration & dosage , Child , Child Mortality , Child, Preschool , Ethiopia/epidemiology , Humans , Infant , Infant Mortality , Rural Population , Trachoma/drug therapy , Trachoma/mortality , Treatment Outcome
12.
Ophthalmology ; 116(11): 2047-50, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19744717

ABSTRACT

OBJECTIVE: To determine whether infectious trachoma can be completely eliminated from severely affected villages. DESIGN: Cross-sectional survey of 2 villages previously enrolled and monitored over 42 months as part of a larger, group-randomized clinical trial. PARTICIPANTS: A total of 758 individuals residing in 2 villages with high baseline trachoma prevalence, of a total population of 768 (98.7%). METHODS: All members of the 2 villages were offered 6 biannual mass treatments with oral azithromycin. At 42 months, each current village member was examined. The right upper tarsal conjunctiva was everted and swabbed. Samples were processed for evidence of Chlamydia trachomatis RNA. MAIN OUTCOME MEASURES: Clinical activity by World Health Organization simplified grading scale for trachoma and laboratory evidence of chlamydial RNA. RESULTS: Average antibiotic coverage over the study period was 90% and 94% in the 2 villages. Clinical trachoma activity in children aged 1 to 5 years decreased from 78% and 83% in the 2 villages before treatment to 17% and 24% at 42 months. Polymerase chain reaction (PCR) evidence of infection in the same age group decreased from 48% to 0% in both villages at 42 months. When all age groups were examined, there were zero cases with evidence of chlamydial RNA among 758 total villagers tested. CONCLUSIONS: Biannual mass distribution of azithromycin can locally eliminate ocular chlamydial infection from severely affected communities.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Azithromycin/administration & dosage , Trachoma/drug therapy , Administration, Oral , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Chlamydia trachomatis/genetics , Chlamydia trachomatis/isolation & purification , Conjunctiva/microbiology , Cross-Sectional Studies , Ethiopia/epidemiology , Female , Humans , Infant , Infant, Newborn , Male , Mass Screening , Middle Aged , Polymerase Chain Reaction , Prevalence , RNA, Bacterial/analysis , Rural Population , Trachoma/epidemiology , Trachoma/microbiology , Young Adult
13.
PLoS Negl Trop Dis ; 3(8): e507, 2009 Aug 25.
Article in English | MEDLINE | ID: mdl-19707573

ABSTRACT

BACKGROUND: As part of the SAFE strategy, mass antibiotic treatments are useful in controlling the ocular strains of chlamydia that cause trachoma. The World Health Organization recommends treating at least 80% of individuals per community. However, the role of antibiotic coverage for trachoma control has been poorly characterized. METHODOLOGY/PRINCIPAL FINDINGS: In a collection of cluster-randomized clinical trials, mass oral azithromycin was administered to 40 villages in Ethiopia. The village prevalence of ocular chlamydia was determined before treatment, and at two and six months post-treatment. The mean prevalence of ocular chlamydia was 48.9% (95% CI 42.8 to 55.0%) before mass treatments, decreased to 5.4% (95% CI 3.9 to 7.0%) at two months after treatments (p<0.0001), and returned to 7.9% (95% CI 5.4 to 10.4%) by six months after treatment (p = 0.03). Antibiotic coverage ranged from 73.9% to 100%, with a mean of 90.6%. In multivariate regression models, chlamydial prevalence two months after treatment was associated with baseline infection (p<0.0001) and antibiotic coverage (p = 0.007). However, by six months after treatment, chlamydial prevalence was associated only with baseline infection (p<0.0001), but not coverage (p = 0.31). CONCLUSIONS/SIGNIFICANCE: In post-hoc analyses of a large clinical trial, the amount of endemic chlamydial infection was a strong predictor of chlamydial infection after mass antibiotic treatments. Antibiotic coverage was an important short-term predictor of chlamydial infection, but no longer predicted infection by six months after mass antibiotic treatments. A wider range of antibiotic coverage than found in this study might allow an assessment of a more subtle association.

14.
Emerg Infect Dis ; 15(7): 1088-90, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19624926

ABSTRACT

We investigated antimicrobial drug resistance in ocular Chlamydia trachomatis 18 months after 4 biannual communitywide distributions of antimicrobial drugs in a region of Ethiopia where ocular strains of C. trachomatis are highly endemic. We found no significant differences in susceptibilities to azithromycin and doxycycline in 6 posttreatment and 4 pretreatment samples.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Chlamydia trachomatis/drug effects , Drug Resistance, Microbial/genetics , Eye Diseases/microbiology , Administration, Topical , Adult , Child , Child, Preschool , Chlamydia trachomatis/genetics , Cycloheximide/pharmacology , Ethiopia/epidemiology , Eye Diseases/drug therapy , Eye Diseases/epidemiology , Female , Genetic Predisposition to Disease , Humans , Infant , Male , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Prevalence
15.
Lancet ; 373(9669): 1111-8, 2009 Mar 28.
Article in English | MEDLINE | ID: mdl-19329003

ABSTRACT

BACKGROUND: Trachoma-control programmes distribute oral azithromycin to treat the ocular strains of chlamydia that cause the disease and to control infection. Theoretically, elimination of infection is feasible if untreated individuals receive an indirect protective effect from living in repeatedly treated communities, which is similar to herd protection in vaccine programmes. We assessed indirect protection against trachoma with mass azithromycin distributions. METHODS: In a cluster randomised trial, 24 subkebeles (government-defined units) in Amhara, Ethiopia, were randomised, with use of a simple random sample, to distribution four times per year of single-dose oral azithromycin to children aged 1-10 years (12 subkebeles, 4764 children), or to delayed treatment until after the study (control; 12 subkebeles, 6014 children). We compared the prevalence of ocular chlamydial infection in untreated individuals 11 years and older between baseline and 12 months in the treated subkebeles, and at 12 months between the treated and control subkebeles. Health-care and laboratory personnel were blinded to study group. Analysis was intention to treat. The study is registered with clinicaltrials.gov, number NCT00322972. FINDINGS: At 12 months, 637 children aged 1-10 years and 561 adults and children aged 11 years and older were analysed in the children-treated group, and 618 and 550, respectively, in the control group. The mean prevalence of infection in children decreased from 48.4% (95% CI 42.9-53.9) to 3.6% (0.8-6.4) after four mass treatments. At 12 months, the mean prevalence of infection in the untreated age group (>/=11 years) was 47% (95% CI 33-57) less than baseline (p=0.002), and 35% (95% CI 1-57) less than that in untreated communities (p=0.04). INTERPRETATION: Frequent treatment of children, who are a core group for transmission of trachoma, could eventually eliminate infection from the entire community. Herd protection is offered by repeated mass antibiotic treatments, providing a strategy for elimination of a bacterial disease when an effective vaccine is unavailable. FUNDING: National Institutes of Health.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Azithromycin/administration & dosage , Trachoma/prevention & control , Child , Child, Preschool , Female , Humans , Male , Trachoma/drug therapy
16.
PLoS Negl Trop Dis ; 3(2): e376, 2009.
Article in English | MEDLINE | ID: mdl-19190781

ABSTRACT

BACKGROUND: Antibiotics are a major tool in the WHO's trachoma control program. Even a single mass distribution reduces the prevalence of the ocular chlamydia that causes trachoma. Unfortunately, infection returns after a single treatment, at least in severely affected areas. Here, we test whether additional scheduled treatments further reduce infection, and whether infection returns after distributions are discontinued. METHODS: Sixteen communities in Ethiopia were randomly selected. Ocular chlamydial infection in 1- to 5-year-old children was monitored over four biannual azithromycin distributions and for 24 months after the last treatment. FINDINGS: The average prevalence of infection in 1- to 5-year-old children was reduced from 63.5% pre-treatment to 11.5% six months after the first distribution (P<0.0001). It further decreased to 2.6% six months after the fourth and final treatment (P = 0.0004). In the next 18 months, infection returned to 25.2%, a significant increase from six months after the last treatment (P = 0.008), but still far lower than baseline (P<0.0001). Although the prevalence of infection in any particular village fluctuated, the mean prevalence of the 16 villages steadily decreased with each treatment and steadily returned after treatments were discontinued. CONCLUSION: In some of the most severely affected communities ever studied, we demonstrate that repeated mass oral azithromycin distributions progressively reduce ocular chlamydial infection in a community, as long as these distributions are given frequently enough and at a high enough coverage. However, infection returns into the communities after the last treatment. Sustainable changes or complete local elimination of infection will be necessary. TRIAL REGISTRATION: ClinicalTrials.gov NCT00221364.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Trachoma/drug therapy , Anti-Bacterial Agents/administration & dosage , Azithromycin/administration & dosage , Child, Preschool , Drug Administration Schedule , Ethiopia/epidemiology , Female , Humans , Infant , Male , Pregnancy , Treatment Outcome
17.
Invest Ophthalmol Vis Sci ; 50(1): 90-4, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18689701

ABSTRACT

PURPOSE: Trachoma remains the leading infectious cause of blindness worldwide. The World Health Organization (WHO) recommends mass antibiotic distributions in its strategy to eliminate blinding trachoma. To determine the most effective antibiotic treatment strategy, it is essential to have a diagnostic test that can correctly measure the true status of ocular Chlamydia trachomatis infection in individuals, particularly after treatment. A newer ribosomal ribonucleic acid (rRNA)-based amplification test was compared with the current DNA-based polymerase chain reaction (PCR) for the detection of C. trachomatis. METHODS: An rRNA-based assay and PCR were performed on swab specimens taken from the right upper tarsal conjunctiva of 240 children aged 1 to 5 years living among 16 endemic villages in the Gurage Zone, Ethiopia. RESULTS: The rRNA-based test detected ocular C. trachomatis infection in 142 (59%) subjects compared with 67 (28%) detected by PCR (McNemar's test, P < 0.0001). The rRNA-based test gave positive results for all subjects who were positive by PCR and detected infection in 75 (31%) additional subjects. CONCLUSIONS: The rRNA-based test appears to have significantly greater sensitivity than PCR for the detection of ocular C. trachomatis infection in children in trachoma-endemic villages. The increased sensitivity of the rRNA-based test may be due to its ability to detect low levels of C. trachomatis infection in individuals, which can occur especially after antibiotic treatment. Data from past studies in which PCR was used to assess the prevalence of infectious trachoma after community-wide antibiotic treatments could have underestimated the true prevalence of infection.


Subject(s)
Chlamydia trachomatis/isolation & purification , Endemic Diseases , Nucleic Acid Amplification Techniques/methods , RNA, Bacterial/analysis , Trachoma/diagnosis , Trachoma/epidemiology , Child, Preschool , Chlamydia trachomatis/genetics , Conjunctiva/microbiology , Ethiopia/epidemiology , Female , Humans , Infant , Male , Polymerase Chain Reaction , RNA, Ribosomal, 16S/genetics , Trachoma/microbiology
18.
JAMA ; 299(7): 778-84, 2008 Feb 20.
Article in English | MEDLINE | ID: mdl-18285589

ABSTRACT

CONTEXT: Treatment recommendations assume that repeated mass antibiotic distributions can control, but not eradicate or even locally eliminate, the ocular strains of chlamydia that cause trachoma. Elimination may be an important end point because of concern that infection will return to communities that have lost immunity to chlamydia after antibiotics are discontinued. OBJECTIVE: To determine whether biannual treatment can eliminate ocular chlamydial infection from preschool children and to compare results with the World Health Organization-recommended annual treatment. DESIGN, SETTING, AND PARTICIPANTS: A cluster-randomized clinical trial of biannual vs annual mass azithromycin administrations to all residents of 16 rural villages in the Gurage Zone, Ethiopia, from March 2003 to April 2005. INTERVENTIONS: At scheduled treatments, all individuals aged 1 year or older were offered a single dose of oral azithromycin either annually or biannually. MAIN OUTCOME MEASURE: Village prevalence of ocular chlamydial infection and presence of elimination at 24 months in preschool children determined by polymerase chain reaction, correcting for baseline prevalence. Antibiotic treatments were performed after sample collections. RESULTS: Overall, 14,897 of 16,403 eligible individuals (90.8%) received their scheduled treatment. In the villages in which residents were treated annually, the prevalence of infection in preschool children was reduced from a mean of 42.6% (range, 14.7%-56.4%) to 6.8% (range, 0.0%-22.0%) at 24 months. In the villages in which residents were treated biannually, infection was reduced from 31.6% pretreatment (range, 6.1%-48.6%) to 0.9% (range, 0.0%-4.8%) at 24 months. Biannual treatment was associated with a lower prevalence at 24 months (P = .03, adjusting for baseline prevalence). At 24 months, no infection could be identified in 6 of 8 of those treated biannually and in 1 of 8 of those treated annually (P = .049, adjusting for baseline prevalence). CONCLUSION: Local elimination of ocular chlamydial infection appears feasible even in the most severely affected areas, although it may require biannual mass antibiotic distributions at a high coverage level. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00221364.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Azithromycin/administration & dosage , Trachoma/drug therapy , Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Child, Preschool , Female , Humans , Infant , Male
19.
Clin Infect Dis ; 46(4): 564-6, 2008 Feb 15.
Article in English | MEDLINE | ID: mdl-18194094

ABSTRACT

The World Health Organization has distributed millions of doses of azithromycin to control the ocular chlamydial infection that causes trachoma. Theoretically, a loftier goal of elimination is feasible. Here, we demonstrate that, although local elimination of infection in the most severely affected communities is difficult, it is possible with biannual antibiotic distributions.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Infection Control/methods , Trachoma/drug therapy , Trachoma/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Ethiopia , Female , Humans , Infant , Male , Middle Aged , Rural Population , Tetracycline/therapeutic use
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