Mass azithromycin distribution is a core component of trachoma control programmes and could reduce mortality in children younger than 5 years in some settings. In this systematic review we synthesise ...evidence on the emergence of antimicrobial resistance after mass azithromycin distribution. We searched electronic databases for publications up to June 14, 2018. We included studies of any type (excluding modelling studies, surveillance reports, and review articles) on community-wide distribution of oral azithromycin for the prevention and treatment of trachoma that assessed macrolide resistance, without restrictions to the type of organism. We extracted prevalence of resistance from published reports and requested unpublished data from authors of included studies. Of 213 identified studies, 19 met inclusion criteria (12 assessed Streptococcus pneumoniae) and were used for qualitative synthesis. Macrolide resistance after azithromycin distribution was reported in three of the five organisms studied. The lack of resistance in Chlamydia trachomatis suggests that azithromycin might remain effective for trachoma programmes, but evidence is scarce. As mass azithromycin distribution for trachoma continues and is considered for other indications, ongoing monitoring of antimicrobial resistance will be required.
BackgroundTo facilitate mass distribution of azithromycin, trachoma control programmes use height instead of weight to determine dose for children 6 months to 15 years old. WHO has recommended ...azithromycin distribution to children 1–11 months old to reduce mortality in high mortality settings under carefully monitored conditions. Weight was used to determine dose in children 1–5 months old in studies of azithromycin distribution for child survival, but a simplified approach using age or height for all aged 1–11 months old could increase programme efficiency in real-world settings.MethodsThis secondary analysis used data from two cluster randomised trials of azithromycin distribution for child mortality in Niger and Burkina Faso. An exhaustive search algorithm was developed to determine the optimal dose for different age groups, using tolerance limits of 10–20 mg/kg for children 1–2 months old and 15–30 mg/kg for children 3–11 months old. Height-based dosing was evaluated against the existing trachoma dosing pole and with a similar exhaustive search.ResultsThe optimal two-tiered age-based approach suggested a dose of 80 mg (2 mL) for children 1–2 months old and 160 mg (4 mL) for children 3–11 months old. Under this schedule, 89%–93% of children would have received doses within tolerance limits in both study populations. Accuracy was 93%–94% with a three-tiered approach, which resulted in doses of 80 mg (2 mL), 120 mg (3 mL) and 160 mg (4 mL) for children 1–2, 3–4 and 5–11 months old, respectively. For children 1–5 months old, the existing height pole would result in 70% of doses within tolerance limits. The optimisation identified height-based dosing options with 95% accuracy, although this would require changes to the existing dosing pole as well as additional training to measure infants lying flat.ConclusionsOverall, an age-based approach with two age tiers resulted in high accuracy while considering both concerns about overdosing in this young population and simplicity of field operations.
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.
Importance Because transmission of ocular strains ofChlamydia trachomatisis greatest among preschool-aged children, limiting azithromycin distributions to this age group may conserve resources and ...result in less antimicrobial resistance, which is a potential advantage in areas with hypoendemic trachoma and limited resources. Objective To determine the efficacy of mass azithromycin distributions to preschool-aged children as a strategy for trachoma elimination in areas with hypoendemic disease. Design, Setting, and Participants In this cluster randomized clinical trial performed from November 23, 2014, until July 31, 2017, thirty rural communities in Niger were randomized at a 1:1 ratio to biannual mass distributions of either azithromycin or placebo to children aged 1 to 59 months. Participants and study personnel were masked to treatment allocation. Data analyses for trachoma outcomes were performed from October 19, 2021, through June 10, 2022. Interventions Every 6 months, a single dose of either oral azithromycin (20 mg/kg using height-based approximation for children who could stand or weight calculation for small children) or oral placebo was provided to all children aged 1 to 59 months. Main Outcomes and Measures Trachoma was a prespecified outcome of the trial, assessed as the community-level prevalence of trachomatous inflammation–follicular and trachomatous inflammation–intense through masked grading of conjunctival photographs from a random sample of 40 children per community each year during the 2-year study period. A secondary outcome was the seroprevalence of antibodies toC trachomatisantigens. Results At baseline, 4726 children in 30 communities were included; 1695 children were enrolled in 15 azithromycin communities and 3031 children were enrolled in 15 placebo communities (mean SD proportions of boys, 51.8% 4.7% vs 52.0% 4.2%; mean SD age, 30.8 2.8 vs 30.6 2.6 months). The mean coverage of study drug for the 4 treatments was 79% (95% CI, 75%-83%) in the azithromycin group and 82% (95% CI, 79%-85%) in the placebo group. The mean prevalence of trachomatous inflammation–follicular at baseline was 1.9% (95% CI, 0.5%-3.5%) in the azithromycin group and 0.9% (95% CI, 0-1.9%) in the placebo group. At 24 months, trachomatous inflammation–follicular prevalence was 0.2% (95% CI, 0-0.5%) in the azithromycin group and 0.8% (95% CI, 0.2%-1.6%) in the placebo group (incidence rate ratio adjusted for baseline: 0.18 95% CI, 0.01-1.20; permutationP = .07). Conclusions and Relevance The findings of this trial do not show that biannual mass azithromycin distributions to preschool-aged children were more effective than placebo, although the underlying prevalence of trachoma was low. The sustained absence of trachoma even in the placebo group suggests that trachoma may have been eliminated as a public health problem in this part of Niger. Trial Registration ClinicalTrials.gov Identifier:NCT02048007
Mass azithromycin distributions may decrease childhood mortality, although the causal pathway is unclear. The potential for antibiotics to function as growth promoters may explain some of the ...mortality benefit.
To investigate whether biannual mass azithromycin distributions are associated with increased childhood growth.
This cluster-randomized trial was performed from December 2014 until March 2020 among 30 rural communities in Boboye and Loga departments in Niger, Africa, with populations from 200 to 2000 individuals. Communities were randomized in a 1:1 ratio to biannual mass distributions of azithromycin or placebo for children ages 1 to 59 months. Participants, field-workers, and study personnel were masked to treatment allocation. Height and weight changes from baseline to follow-up at 4 years were compared between groups. Data were analyzed from June through November 2021.
Participants received azithromycin at 20 mg/kg using height-based approximation or by weight for children unable to stand every 6 months at the participants' households. Placebo contained the vehicle of the azithromycin suspension.
Longitudinal anthropometric assessments were performed on a random sample of children before the first treatment and then annually for 5 years. Height and weight were the prespecified primary outcomes.
Among 3936 children enrolled from 30 communities, baseline characteristics were similar between 1299 children in the azithromycin group and 2637 children in the placebo group (mean 48.2% 95% CI, 45.5% to 50.8% girls vs 48.0% 95% CI, 45.7% to 50.3% girls; mean age, 30.8 months 95% CI, 29.5 to 32.0 months vs 30.6 months 95% CI, 29.2 to 31.6 months). Baseline anthropometric assessments were performed among 2230 children, including 985 children in the azithromycin group and 1245 children in the placebo group, of whom follow-up measurements were available for 789 children (80.1%) and 1063 children (85.4%), respectively. At the prespecified 4-year follow-up visit, children in the azithromycin group gained a mean 6.7 cm (95% CI, 6.5 to 6.8 cm) in height and 1.7 kg (95% CI, 1.7 to 1.8 kg) in weight per year and children in the placebo group gained a mean 6.6 cm (95% CI, 6.4 to 6.7 cm) in height and 1.7 kg (95% CI, 1.7 to 1.8 kg) in weight per year. Height at 4 years was not statistically significantly different between groups when adjusted for baseline height (0.08 cm 95% CI, -0.12 to 0.28 cm greater in the azithromycin group; P = .45), and neither was weight when adjusted for height and baseline weight (0.02 kg 95% CI, -0.10 to 0.06 kg less in the azithromycin group; P = .64). However, among children in the shortest quartile of baseline height, azithromycin was associated with a 0.4 cm (95% CI, 0.1 to 0.7 cm) increase in height compared with placebo.
This study did not find evidence of an association between mass azithromycin distributions and childhood growth, although subgroup analysis suggested some benefit for the shortest children. These findings suggest that the mortality benefit of mass azithromycin distributions is unlikely to be due solely to growth promotion.
ClinicalTrials.gov Identifier: NCT02048007.
Triploid Suminoe oysters,
Crassostrea ariakensis, are currently being considered for culture on the mid Atlantic coast of the USA. Despite studies comparing the performance of
C. ariakensis with the ...native oyster,
Crassostrea virginica, at the grow-out stage, growth and mortality of
C. ariakensis and
C. virginica have not been compared during nursery rearing in upwellers. If, as in grow-out bags, triploid
C. ariakensis in upwellers grow at significantly faster rates than diploid
C. virginica, they may suffer food limitation in intensive nursery systems at flows and densities where diploid
C. virginica do not. If a consequence of the rapid growth of
C. ariakensis is a thinner shell with greater susceptibility to boring worms, it may require potentially stressful treatment against
Polydora spp. These hypotheses were tested in an orthogonal experiment, done in fall 2003, in which triploid
C. ariakensis and diploid
C. virginica were grown in upwellers with high (11.34×10
−3 m
3 s
−1) or low flow (3.56×10
−3 m
3 s
−1), that were treated or untreated against
Polydora spp. (by hypersaline dip and drying) and stocked at high or low densities. In the first 2 weeks of the experiment, during which both species grew rapidly, growth of
C. ariakensis was up to seven times greater than
C. virginica. This difference was reduced in subsequent weeks, when water temperature began to decrease and rates of growth of each species slowed. Contrary to expectation, neither species displayed sizeable reductions in growth at high as compared to low density. Mortality of
C. ariakensis was, however, 1–2% greater at high than low density.
C. virginica appeared more susceptible to decreased growth at low flow, although the effect of flow in this experiment was small. Both species suffered greatest mortality when previously treated against
Polydora spp. The treatment was, however, effective in reducing infestation, to which
C. virginica, contrary to expectation, appeared most susceptible. Thus, it appears that similar conditions are suitable for the culture of triploid
C. ariakensis in upwellers as for diploid
C. virginica.
Spontaneous hemothorax is an uncommon condition usually associated with trauma, iatrogenic interventions, or rupture of pleural adhesions, and pneumothorax. We report the unique case of spontaneous ...hemothorax in a 35-year-old woman resulting from uterine hemorrhage in whom fenestrations in the diaphragm allowed blood to pass from the abdomen to the chest.
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