Distribution Of Azithromycin Research Articles

Azithromycin Reduces Childhood Deaths in Africa.

According to this study: Mass distribution of oral azithromycin to children in sub-Saharan Africa significantly lowered childhood mortality, as compared with placebo.It is possible that the development of antibiotic resistance could erase the difference, although that effect was not seen in this trial.

Does gonorrhoea screening intensity play a role in the early selection of antimicrobial resistance in men who have sex with men (MSM)? A comparative study of Belgium and the United Kingdom

Background: It is unclear why antimicrobial resistance in Neisseria gonorrhoeae in the United Kingdom (UK) and the United States has tended to first appear in men who have sex with men (MSM). We hypothesize that increased exposure to antimicrobials from intensive STI screening programmes plays a role. Methods: We assess if there is a difference in the distribution of azithromycin, cefixime and ceftriaxone minimum inhibitory concentrations (MICs) between MSM and women in the United Kingdom (UK) where 70% of MSM report STI screening in the past year vs. Belgium where 9% report STI screening in the past year. Our hypothesis is that MICs of the MSM should be higher than those of the women in the UK but not Belgium. Data for the MICs were taken from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in the UK in 2010/2011 and 2014 and a similar national surveillance programme in Belgium in 2013/2014 (the first most complete available data). We used the Mann–Whitney test to compare the MIC distributions between MSM and women within each country Results: In the UK the MICs for all three antimicrobials were significantly higher in MSM than women at both time points (P all <0.0005). In Belgium only the MIC distribution for azithromycin was higher in MSM (P<0.0005). Conclusion: The findings for cefixime and ceftriaxone, but not azithromycin are compatible with our hypothesis that screening-intensity could contribute to the emergence of AMR. Numerous other interpretations of our results are discussed.

Does gonorrhoea screening intensity play a role in the early selection of antimicrobial resistance in men who have sex with men (MSM)? A comparative study of Belgium and the United Kingdom

Background: It is unclear why antimicrobial resistance in Neisseria gonorrhoeae in the United Kingdom (UK) and the United States has tended to first appear in men who have sex with men (MSM). We hypothesize that increased exposure to antimicrobials from intensive STI screening programmes plays a role. Methods: We assess if there is a difference in the distribution of azithromycin, cefixime and ceftriaxone minimum inhibitory concentrations (MICs) between MSM and women in the United Kingdom (UK) where 70% of MSM report STI screening in the past year vs. Belgium where 9% report STI screening in the past year. Our hypothesis is that MICs of the MSM should be higher than those of the women in the UK but not Belgium. Data for the MICs were taken from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in the UK in 2010/2011 and 2014 and a similar national surveillance programme in Belgium in 2013/2014 (the first most complete available data). We used the Mann-Whitneytest to compare the MIC distributions between MSM and women within each country Results: In the UK the MICs for all three antimicrobials were significantly higher in MSM than women at both time points (P all <0.0005). In Belgium only the MIC distribution for azithromycin was higher in MSM (P<0.0005). Conclusion: The findings for cefixime and ceftriaxone, but not azithromycin are compatible with our hypothesis that screening-intensity could contribute to the emergence of AMR. Numerous other interpretations of our results are discussed.

Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa

BackgroundWe hypothesized that mass distribution of a broad-spectrum antibiotic agent to preschool children would reduce mortality in areas of sub-Saharan Africa that are currently far from meeting the Sustainable Development Goals of the United Nations.MethodsIn this cluster-randomized trial, we assigned communities in Malawi, Niger, and Tanzania to four twice-yearly mass distributions of either oral azithromycin (approximately 20 mg per kilogram of body weight) or placebo. Children 1 to 59 months of age were identified in twice-yearly censuses and were offered participation in the trial. Vital status was determined at subsequent censuses. The primary outcome was aggregate all-cause mortality; country-specific rates were assessed in prespecified subgroup analyses.ResultsA total of 1533 communities underwent randomization, 190,238 children were identified in the census at baseline, and 323,302 person-years were monitored. The mean (±SD) azithromycin and placebo coverage over the four twice-yearly distributions was 90.4±10.4%. The overall annual mortality rate was 14.6 deaths per 1000 person-years in communities that received azithromycin (9.1 in Malawi, 22.5 in Niger, and 5.4 in Tanzania) and 16.5 deaths per 1000 person-years in communities that received placebo (9.6 in Malawi, 27.5 in Niger, and 5.5 in Tanzania). Mortality was 13.5% lower overall (95% confidence interval [CI], 6.7 to 19.8) in communities that received azithromycin than in communities that received placebo (P<0.001); the rate was 5.7% lower in Malawi (95% CI, −9.7 to 18.9), 18.1% lower in Niger (95% CI, 10.0 to 25.5), and 3.4% lower in Tanzania (95% CI, −21.2 to 23.0). Children in the age group of 1 to 5 months had the greatest effect from azithromycin (24.9% lower mortality than that with placebo; 95% CI, 10.6 to 37.0). Serious adverse events occurring within a week after administration of the trial drug or placebo were uncommon, and the rate did not differ significantly between the groups. Evaluation of selection for antibiotic resistance is ongoing.ConclusionsAmong postneonatal, preschool children in sub-Saharan Africa, childhood mortality was lower in communities randomly assigned to mass distribution of azithromycin than in those assigned to placebo, with the largest effect seen in Niger. Any implementation of a policy of mass distribution would need to strongly consider the potential effect of such a strategy on antibiotic resistance. (Funded by the Bill and Melinda Gates Foundation; MORDOR ClinicalTrials.gov number, NCT02047981.)

The Epidemiology of Trachoma in Mozambique: Results of 96 Population-Based Prevalence Surveys

ABSTRACTPurpose: Surveys are needed to guide trachoma control efforts in Mozambique, with WHO guidelines for intervention based on the prevalence of trachomatous inflammation–follicular (TF) in children aged 1–9 years and the prevalence of trichiasis in adults aged 15 years and above. We conducted surveys to complete the map of trachoma prevalence in Mozambique.Methods: Between July 2012 and May 2015, we carried out cross-sectional surveys in 96 evaluation units (EUs) covering 137 districts.Results: A total of 269,217 individuals were enumerated and 249,318 people were examined using the WHO simplified trachoma grading system. Overall, 102,641 children aged 1–9 years, and 122,689 individuals aged 15 years and above were examined. The prevalence of TF in children aged 1–9 years was ≥10% in 12 EUs, composed of 20 districts, covering an estimated total population of 2,455,852. These districts require mass distribution of azithromycin for at least 3 years before re-survey. The TF prevalence in children was 5.0–9.9% in 17 EUs (28 districts, total population 3,753,039). 22 EUs (34 districts) had trichiasis prevalences ≥0.2% in adults 15 years and above, and will require public health action to provide surgical services addressing the backlog of trichiasis. Younger age, more children resident in the household, and living in a household that had an unimproved latrine or no latrine facility, were independently associated with an increased odds of TF in children aged 1–9 years.Conclusions: Trachoma represents a significant public health problem in many areas of Mozambique.

Exploratory ocular surface distribution studies of Azithromycin formulations based on semifluorinated alkanes

PurposeAzithromycin is an antimicrobial agent with broad spectrum activity and anti‐inflammatory properties. The aim of this study was to investigate the ocular distribution of azithromycin after a single topical instillation of a new semifluorinated alkane (SFA) based formulation in rabbits.MethodsRabbits were treated with either a single administration of 1.5% or 3% SFA‐azithromycin suspensions. Due to the low surface and interface tension of the SFA, and its excellent spreading properties, droplet size is smaller compared to other ophthalmic formulations which lead to a low instillation volume of ~11 μL. Tears (T), aqueous humor (AH), cornea (C), bulbar conjunctiva (BCJ), and eyelids (EL) from individual eyes were collected up to 144 h post dosing and drug concentrations were measured using a validated LC‐MS/MS method.ResultsFollowing a single topical instillation of SFA‐azithromycin in rabbit eyes, both formulations were macroscopically well tolerated. The highest exposure was found in the general order of EL &gt; T &gt; C &gt; BCJ &gt; AH. The obtained values were compared with data from a similar experiment of a marketed 1.5% azithromycin formulation in medium‐chain triglycerides1, with a single instillation of 25 μL. The comparison showed that azithromycin exposure after administration of 1.5% SFA‐azithromycin formulation was similar to the marketed formulation despite the lower absolute dose.Amar et al, Current Eye Research, 33: 149‐158, 2008ConclusionsThe preservative‐free, multi‐dose SFA‐azithromycin formulation was well tolerated. Both concentrations resulted in adequate and long‐lasting azithromycin levels in T and EL, C and BCJ. Based on these results this azithromycin formulation may lead to a new therapeutic well‐tolerated option in treating ocular surface bacterial infections.

Antibiotic Resistance in Young Children in Kilosa District, Tanzania 4 Years after Mass Distribution of Azithromycin for Trachoma Control.

Mass administration of azithromycin (MDA) is integral to trachoma control. Recent studies suggest that MDA may increase drug-resistant pathogens, yet findings from prior studies suggest little long-term impact on resistance. This disparity may be linked to differences in pre-MDA community-level resistance patterns. We describe carriage prevalence and antibiotic resistance patterns for Streptococcus pneumoniae (Spn) (nasopharyngeal swab collection), Staphylococcus aureus (SA) (nasopharyngeal swabs), and Escherichia coli (EC) (rectal swabs) in 1,047 children ages 1-59 months in a district with MDA cessation 4 years ago. Antibiotic susceptibility was evaluated by disk diffusion and Etest. The carriage rates for Spn, SA, and EC were 43.5% (455/1,047), 13.2% (138/1,047), and 61.7% (646/1,047), respectively. Resistance to AZM was observed in 14.3%, 29.0%, and 16.6% of the Spn, SA, and EC isolates, respectively. Spn resistance was variable (0-67%) by hamlet. Future analyses will assess the influence of pre-MDA antibiotic resistance patterns on those observed following MDA.

Mapping Trachoma in the Solomon Islands: Results of Three Baseline Population-Based Prevalence Surveys Conducted with the Global Trachoma Mapping Project

ABSTRACTPurpose: We sought to complete the baseline trachoma map of the Solomon Islands by establishing prevalences of active trachoma and trichiasis in the provinces of Choiseul, Western, Rennell-Bellona, and Temotu.Methods: Using the standardized methodology developed for the Global Trachoma Mapping Project, we conducted cross-sectional community-based surveys from September to November 2013. Choiseul and Western provinces were each mapped as separate evaluation units (EUs); Rennell-Bellona and Temotu were combined to form a third EU.Results: A total of 9819 individuals were sampled for inclusion, with 9224 (93.3%) consenting to examination, of whom 4587 (46.3%) were female. Survey teams visited 82 villages, and surveyed 2448 households. Two EUs had prevalences of trachomatous inflammation – follicular (TF) in 1–9-year-olds over the 10% threshold at which WHO recommends mass distribution of azithromycin for at least 3 years (Western 20.4%, 95% confidence interval, CI 15.6–26.3%; Rennell-Bellona/Temotu 22.0%, 95% CI 18.5–26.0%). Choiseul had a TF prevalence of 6.1% (95% CI 4.1–8.6%), and met the criterion for a single round of mass antibiotic distribution before re-survey. The adjusted prevalences of trichiasis in those aged 15+ years were 0.0% (95% CI 0.0–0.2%) in Choiseul, 0.16% (95% CI 0.0–0.5%) in Western, and 0.10% (95% CI 0–0.3%) in Rennell-Bellona/Temotu provinces. All three EUs require implementation of the facial cleanliness and environmental improvement components of the trachoma elimination strategy.Conclusion: Active trachoma is prevalent in the Solomon Islands. However, there is little evidence of the blinding complications of trachoma being a public health problem there. Further research into the explanation for this phenomenon is warranted.

Higher organism load associated with failure of azithromycin to treat rectal chlamydia.

Repeat rectal chlamydia infection is common in men who have sex with men (MSM) following treatment with 1 g azithromycin. This study describes the association between organism load and repeat rectal chlamydia infection, genovar distribution, and efficacy of azithromycin in asymptomatic MSM. Stored rectal chlamydia-positive samples from MSM were analysed for organism load and genotyped to assist differentiation between reinfection and treatment failure. Included men had follow-up tests within 100 days of index infection. Lymphogranuloma venereum and proctitis diagnosed symptomatically were excluded. Factors associated with repeat infection, treatment failure and reinfection were investigated. In total, 227 MSM were included - 64 with repeat infections [28·2%, 95% confidence interval (CI) 22·4-34·5]. Repeat positivity was associated with increased pre-treatment organism load [odds ratio (OR) 1·7, 95% CI 1·4-2·2]. Of 64 repeat infections, 29 (12·8%, 95% CI 8·7-17·8) were treatment failures and 35 (15·4%, 95% CI 11·0-20·8) were reinfections, 11 (17·2%, 95% CI 8·9-28·7) of which were definite reinfections. Treatment failure and reinfection were both associated with increased load (OR 2·0, 95% CI 1·4-2·7 and 1·6, 95% CI 1·2-2·2, respectively). The most prevalent genovars were G, D and J. Treatment efficacy for 1 g azithromycin was 83·6% (95% CI 77·2-88·8). Repeat positivity was associated with high pre-treatment organism load. Randomized controlled trials are urgently needed to evaluate azithromycin's efficacy and whether extended doses can overcome rectal infections with high organism load.

High azithromycin concentration in lungs by way of bovine serum albumin microspheres as targeted drug delivery: lung targeting efficiency in albino mice.

BackgroundFollowing administration, the antibiotic travels freely through the body and also accumulates in other parts apart from the infection site. High dosage and repeated ingestion of antibiotics in the treatment of pneumonia leads to undesirable effects and inappropriate disposition of the drug. By way of targeted lung delivery, this study was intended to eliminate inappropriate azithromycin disposition and to achieve higher azithromycin concentration to treat deeper airway infections.MethodsThe Azithromycin Albumin Microspheres (AAM) was prepared by emulsion polymerization technique. The optimized AAM was subjected to in vitro release study, release kinetics, XRD and stability studies. Further, in vivo pharmacokinetics and tissue distribution of azithromycin released from AAM and azithromycin solution in albino mice was investigated to prove suitability of moving forward the next steps in the clinic.ResultsThe mean particle size of the optimized AAM was 10.02 μm, an optimal size to get deposited in the lungs by mechanical entrapment. The maximum encapsulation efficiency of 82.3 % was observed in this study. The release kinetic was significant and best fitted for Korsmeyer-Peppas model (R2 = 0.9962, n = 0.41). The XRD and stability study showed favorable results. Azithromycin concentration in mice lungs (40.62 μg g−1, 30 min) of AAM was appreciably higher than other tissues and plasma. In comparison with control, azithromycin concentration in lungs was 30.15 μg g−1 after 30 min. The azithromycin AUC (929.94 μg h mL−1) and intake rate (re) (8.88) for lung were higher and statistically significant in AAM group. Compared with spleen and liver, the targeting efficacy (te) in mice lung increased by a factor of 40.15 and ~14.10 respectively. Subsequently by a factor of 8.94, the ratio of peak concentration (Ce) in lung was higher in AAM treated mice. The AAM lung tissue histopathology did not show any degenerative changes.ConclusionsHigh azithromycin concentration in albino mice lung was adequately achieved by targeted drug delivery.

A cross-sectional study of 'yaws' in districts of Ghana which have previously undertaken azithromycin mass drug administration for trachoma control.

Yaws, caused by Treponema pallidum ssp. pertenue, is reportedly endemic in Ghana. Mass distribution of azithromycin is now the cornerstone of the WHO yaws eradication campaign. Mass distribution of azithromycin at a lower target dose was previously undertaken in two regions of Ghana for the control of trachoma. Ongoing reporting of yaws raises the possibility that resistance may have emerged in T. pallidum pertenue, or that alternative infections may be responsible for some of the reported cases. We conducted a cross-sectional survey in thirty communities in two districts of Ghana where MDA for trachoma had previously been conducted. Children aged 5–17 years with ulcerative lesions compatible with yaws were enrolled. Samples for treponemal serology and lesion PCR were collected from all children. 90 children with 98 lesions were enrolled. Syphilis serology was negative in all of them. PCR for T. pallidum ssp pertenue was negative in all children, but Haemophilus ducreyi DNA was detected in 9 lesions. In these communities, previously treated for trachoma, we found no evidence of ongoing transmission of yaws. H. ducreyi was associated with a proportion of skin lesions, but the majority of lesions remain unexplained. Integration of diagnostic testing into both pre and post-MDA surveillance systems is required to better inform yaws control programmes.

Antibiotic Resistance in Streptococcus pneumoniae after Azithromycin Distribution for Trachoma.

Trachoma is caused by Chlamydia trachomatis and is a leading cause of blindness worldwide. Mass distribution of azithromycin (AZM) is part of the strategy for the global elimination of blinding trachoma by 2020. Although resistance to AZM in C. trachomatis has not been reported, there have been concerns about resistance in other organisms when AZM is administered in community settings. We identified studies that measured pneumococcal prevalence and resistance to AZM following mass AZM provision reported up to 2013 in Medline and Web of Science databases. Potential sources of bias were assessed using the Cochrane Risk of Bias Tool. A total of 45 records were screened, of which 8 met the inclusion criteria. We identified two distinct trends of resistance prevalence, which are dependent on frequency of AZM provision and baseline prevalence of resistance. We also demonstrated strong correlation between the prevalence of resistance at baseline and at 2-3 months (r = 0.759). Although resistance to AZM in C. trachomatis has not been reported, resistance to this commonly used macrolide antibiotic in other diseases could compromise treatment. This should be considered when planning long-term trachoma control strategies.

Development of a population pharmacokinetic model characterizing the tissue distribution of azithromycin in healthy subjects.

Recent clinical trials indicate that the use of azithromycin is associated with the emergence of macrolide resistance. The objective of our study was to simultaneously characterize free target site concentrations and correlate them with the MIC90s of clinically relevant pathogens. Azithromycin (500 mg once daily [QD]) was administered orally to 6 healthy male volunteers for 3 days. The free concentrations in the interstitial space fluid (ISF) of muscle and subcutaneous fat tissue as well as the total concentrations in plasma and polymorphonuclear leukocytes (PMLs) were determined on days 1, 3, 5, and 10. All concentrations were modeled simultaneously in NONMEM 7.2 using a tissue distribution model that accounts for nonlinear protein binding and ionization state at physiological pH. The model performance and parameter estimates were evaluated via goodness-of-fit plots and nonparametric bootstrap analysis. The model we developed described the concentrations at all sampling sites reasonably well and showed that the overall pharmacokinetics of azithromycin is driven by the release of the drug from acidic cell/tissue compartments. The model-predicted unionized azithromycin (AZM) concentrations in the cytosol of PMLs (6.0 ± 1.2 ng/ml) were comparable to the measured ISF concentrations in the muscle (8.7 ± 2.9 ng/ml) and subcutis (4.1 ± 2.4 ng/ml) on day 10, whereas the total PML concentrations were >1,000-fold higher (14,217 ± 2,810 ng/ml). The total plasma and free ISF concentrations were insufficient to exceed the MIC90s of the skin pathogens at all times. Our results indicate that the slow release of azithromycin from low pH tissue/cell compartments is responsible for the long terminal half-life of the drug and thus the extended period of time during which free concentrations reside at subinhibitory concentrations.

Increased carriage of macrolide-resistant fecalE. colifollowing mass distribution of azithromycin for trachoma control

Mass drug treatment with azithromycin (MDA) is part of the WHO-endorsed 'SAFE' strategy for trachoma control in endemic communities. MDA has been associated with reduced trachoma prevalence and short-term reductions in other bacterial infections, but can also lead to increased circulation of macrolide-resistant bacteria. We prospectively monitored macrolide resistance in fecal E. coli collected from young children participating in the PRET+ Study in rural Tanzania. MDA was administered in four villages with >10% trachoma prevalence. Four nearby communities with lower trachoma prevalence served as controls. Rectal swabs were collected during cross-sectional surveys performed at baseline, 1, 3 and 6 months after MDA. Fecal E. coli isolates were screened for macrolide susceptibility using disc diffusion and minimum inhibitory concentration methods. Cross-sectional and longitudinal differences in resistance prevalence by MDA exposure were compared using t-tests and logistic regression. There was no difference in the proportion of individuals carrying azithromycin-resistant E. coli at baseline (0.21 vs. 0.16, P > 0.05). Azithromycin resistance carriage prevalence remained stable over follow-up in non-MDA villages but increased sharply in MDA villages (0.61 at 1 month, 0.42 at 3 months and 0.31 at 6 months). MDA exposure was highly associated with azithromycin resistance carriage at 1 month post-MDA (OR 15.27, P < 0.001) and subsequent surveys. Younger age and recent diarrhoea were also associated with increased odds of resistance (P < 0.01). MDA resulted in significantly increased prevalence of macrolide resistance in E. coli. Although MDA is effective for trachoma elimination, it has costs; it is essential to monitor antimicrobial resistance following MDA.

Impact of mass azithromycin distribution on malaria parasitemia during the low-transmission season in Niger: a cluster-randomized trial.

We assessed the effect of mass azithromycin treatment on malaria parasitemia in a trachoma trial in Niger. Twenty-four study communities received treatment during the wet, high-transmission season. Twelve of the 24 communities were randomized to receive an additional treatment during the dry, low-transmission season. Outcome measurements were conducted at the community-level in children < 1-72 months of age in May-June 2011. Parasitemia was higher in the 12 once-treated communities (29.8%, 95% confidence interval [CI] = 21.5-40.0%) than in the 12 twice-treated communities (19.5%, 95% CI = 13.0-26.5%, P = 0.03). Parasite density was higher in once-treated communities (354 parasites/μL, 95% CI = 117-528 parasites/μL) than in twice-treated communities (74 parasites/μL, 95% CI = 41-202 parasites/μL, P = 0.03). Mass distribution of azithromycin reduced malaria parasitemia 4-5 months after the intervention. The results suggest that drugs with antimalaria activity can have long-lasting impacts on malaria during periods of low transmission.

Azithromycin, fluoroquinolone and chloramphenicol resistance of non-chlamydia conjunctival bacteria in rural community of Ethiopia

Aim:To determine profiles of non-chlamydia conjunctival bacteria and their antimicrobial susceptibility from adults who underwent trachomatous trichiasis surgery in rural areas of Ethiopia.Materials and Methods:A cross-sectional study was conducted in rural districts in West Gojjam administrative zone. Conjunctival swabs were collected during surgery and transported using Stuart transport broth (Oxoid, UK). Antibiotic susceptibility of conjunctival isolates was determined using the Kirby-Bauer disc-diffusion method.Results:Non-chlamydia pathogenic bacteria were recovered from conjunctiva of 438 (31%) participants before treatment. The isolated conjunctival bacteria were Staphylococcus aureus, coagulase-negative Staphylococci, Streptococcus group (A, C, F and G), Enterococci, Streptococcus pneumoniae, Moraxella spp., Escherichia coli, Citrobacter spp., Proteus spp., Klebsiella spp., Pseudomonas spp. and Enterobacter spp. Overall, resistance rates of 57.8% to azithromycin and 68.5% to chloramphenicol were found. However, 86-94.4% sensitivity was demonstrated to ciprofloxacin and norfloxacin. Moderate sensitivity rates (61.8-78.4%) were observed to ceftriaxone, tetracycline and cotrimoxazole.Conclusion:Fluoroquinolones that have activity against the majority of bacterial isolates were potent at in vitro. However, unacceptably high levels of resistance to azithromycin and chloramphenicol in rural community indicated a need for further study and antimicrobial resistance surveillance.

Collateral benefits arising from mass administration of azithromycin in the control of active trachoma in resource limited settings

IntroductionThe benefits of the use of antibiotics in the mass treatment for active trachoma and other diseases have been documented, but the secondary effects arising from such a programme have not been fully elucidated. The purpose of this study was to investigate the potential secondary benefits arising from the use of azithromycin in mass treatment of active trachoma in an economically challenged Kenyan nomadic community.MethodsHealth information reports for January 2005 to December 2010 were reviewed to determine the annual trends of infectious diseases in the two districts, Narok and Transmara. The year 2007 was considered as the baseline for mass drug administration (MDA). Odds ratios (OR) were used to describe the association.ResultsThe mass distribution coverage in Narok was 83% in 2008, 74% in 2009 and 63% in 2010. The odds for malaria (OR = 1.13; 95% CI 1.12-1.14), diarrhoeal diseases (OR = 1.04; 95% CI 1.01-1.06), urinary tract infections (UTIs) (OR = 1.21; 95% CI 1.17-1.26), intestinal worms (OR, 4.98; 95% CI 4.68-5.3), and respiratory diseases other than pneumonia (OR, 1.15; 95% CI 1.13-1.16) were higher after three rounds of mass treatment, indicating a better outcome. Before the intervention, there was a reducing trend in the odds for respiratory diseases. In Transmara (control), there was an increase in odds for malaria, respiratory infections, UTIs and intestinal worms. The odds for diarrhoeal diseases, skin diseases and pneumonia decreased throughout the study period.ConclusionMass distribution of azithromycin may have contributed to the decrease in the prevalence of the respiratory infections in Narok District.

Has the NTD community neglected evidence-based policy? PLOS NTDs 2013 expert commentary of the viewpoint by Nagpal S, Sinclair D, Garner P.

In July 2013, PLOS Neglected Tropical Diseases will publish the viewpoint of members of the Cochrane Infectious Diseases Group [1] on the scientific evidence supporting the public-health benefits of preventive chemotherapy [2] in the case of programmes against neglected tropical diseases (NTDs), specifically those for the control and elimination of lymphatic filariasis, onchocerciasis, schistosomiasis, and soil-transmitted helminthiases. This viewpoint presents the group's interpretation of its findings on health interventions using Cochrane systematic reviews of preventive chemotherapy interventions published in recent years, which do not confirm the benefits of the intervention at the community level [3], [4]. However, these reviews were conducted by analyzing data exclusively from randomized controlled trials (RCTs). WHO considers RCTs study designs that have been developed to compare drug efficacy over short-term periods and that are not appropriate for evaluating interventions such as preventive chemotherapy, which should be applied to a population for at least five consecutive years [5]. The main reason for this is that it is almost impossible to organize proper RCTs for preventive chemotherapy interventions because of ethical reasons (it is not ethically acceptable to exclude infected populations from treatment for five years). In addition, the results of RCTs are analyzed on the assumption that because preventive chemotherapy is applied at population level, its benefits should be observed in the entire population; by doing so, the key point is missed: that this strategy is used not because it will benefit the uninfected, but because it is more cost-effective to treat everyone than to select those who are infected [6]. In our view, the limitations of RCTs (and reviews based exclusively on their analysis to conclude on public-health interventions) are proven by the fact that they consistently confirmed the efficacy of preventive chemotherapy medicines (albendazole, mebendazole, praziquantel, ivermectin, and DEC) against the parasites targeted (because RCTs are designed to evaluate such results) but failed to demonstrate their impact on communities (because RCTs are not designed to measure such impacts). We consider the best way to evaluate the benefits of preventive chemotherapy interventions to be through monitoring the impact of a disease control or elimination programme for several years. Whenever long-term interventions are evaluated, the impact of preventive chemotherapy on morbidity is evident. For example, Ramzy et al. [7] showed that five annual rounds of mass drug administration eliminated lymphatic filariasis in endemic communities in Egypt; Traore et al. [8] proved that elimination of onchocerciasis with ivermectin is technically feasible in hyperendemic foci from Mali and Senegal; Sinoun et al. [9] demonstrated the complete elimination of the morbidity caused by schistosomiasis in Cambodia after an eight-year intervention; and Casey et al. [10] showed successful control of soil-transmitted helminthiases and improved haemoglobin levels after 56 months of activities in Viet Nam. Unfortunately, none of these articles merited attention by the authors of this viewpoint, probably because they are not RCTs. We therefore consider the conclusion of the authors of this viewpoint the consequence of a selection bias. Some studies demonstrated that preventive chemotherapy is beneficial not only for the populations targeted but also for future generations: for example, Ottesen et al. [11] calculated that, between 2000 and 2007, mass drug administration prevented lymphatic filariasis in 6.6 million newborns, thus averting in their lifetimes nearly 1.4 million cases of hydrocele, 800,000 cases of lymphoedema, and 4.4 million cases of subclinical disease. In addition, evidence demonstrates that preventive chemotherapy is beneficial for diseases that are not included in WHO's list of neglected tropical diseases, such as scabies, which benefit from the large-scale application of ivermectin [12], and to mortality in general, which was significantly reduced in Ethiopia by the large-scale distribution of azithromycin [13]. Finally, it seems to us ethically unacceptable that infected human populations are not administered medication that is freely available while livestock and companion animals are regularly dewormed every year.

Mass Distribution of Azithromycin for Trachoma Control Is Associated With Increased Risk of Azithromycin-Resistant Streptococcus pneumoniae Carriage in Young Children 6 Months After Treatment

Emerging evidence suggests that the mass distribution of azithromycin for trachoma control (MDA) may increase circulation of macrolide resistance in bacteria associated with severe pediatric infections in treated communities. We examined the effect of MDA on nasopharyngeal carriage of antibiotic-resistant Streptococcus pneumoniae among 1015 young children living in rural Tanzania. MDA with a single dose of oral azithromycin was provided in 4 of 8 communities where trachoma prevalence was ≥10%. Isolates were tested for susceptibility to azithromycin (AZM) and commonly used antibiotics by disk diffusion and Etest. We calculated the proportion of antibiotic-resistant S. pneumoniae carriage at baseline and again 1, 3, and 6 months after treatment, and at comparable intervals in the untreated villages. The proportion of AZM-resistant isolates was similar between groups at baseline (MDA: 35.8% vs non-MDA: 35.4%), however, this proportion was greater in the MDA group in all subsequent surveys. At 6 months, the percentage of AZM-resistant isolates was significantly higher in the MDA group (81.9% vs 46.9%, P < .001). The odds of AZM-resistant carriage was 5-fold greater in the MDA group (odds ratio, 4.95 [95% confidence interval, 3.23-7.61]). The proportion of isolates clinically resistant to AZM (minimum inhibitory concentration ≥16 µg/mL) was also significantly greater in the MDA group at 6 months (35.3% vs 12.4%, P < .006). Mass distribution of a single dose of oral azithromycin for trachoma was associated with increased circulation of macrolide-resistant S. pneumoniae carriage among young children in the 6 months following treatment. It is crucial that changes in antibiotic resistance patterns and their clinical significance in the treatment of severe pediatric infections be assessed in future MDA trials.

Will the SAFE strategy be sufficient to eliminate trachoma by 2020? Puzzlements and possible solutions.

Since the inception of (the Global Elimination of Blinding Trachoma) GET 2020 in 1997 and the implementation of the SAFE strategy a year later, much progress has been made toward lowering the prevalence of trachoma worldwide with elimination of the disease in some countries. However, high recurrence of trichiasis after surgery, difficulty in controlling the reemergence of infection after mass distribution of azithromycin in some communities, the incomplete understanding of environment in relation to the disease, and the difficulty in establishing the prevalence of the disease in low endemic areas are some of the issues still facing completion of the GET 2020 goals. In this narrative review, literature was searched from 1998 to January 2013 in PubMed for original studies and reviews. Reasons for these ongoing problems are discussed, and several suggestions are made as avenues for exploration in relation to improving the SAFE strategy with emphasis on improving surgical quality and management of the mass treatment with antibiotics. In addition, more research needs to be done to better understand the approach to improve sanitation, hygiene, and environment. The main conclusion of this review is that scale-up is needed for all SAFE components, and more research should be generated from communities outside of Africa and Asia.