Neonatal azithromycin administration to prevent infant mortality: study protocol for a randomised controlled trial.

IntroductionBiannual mass azithromycin distribution to children aged 1-59 months has been shown to reduce all-cause mortality. Children under 28 days of age were not treated in studies evaluating mass azithromycin distribution for child mortality due to concerns related to infantile hypertrophic pyloric stenosis (IHPS). Here, we report the design of a randomised controlled trial to evaluate the efficacy and safety of administration of a single dose of oral azithromycin during the neonatal period.Methods and analysisThe Nouveaux-nés et Azithromycine: une Innovation dans le Traitement des Enfants (NAITRE) study is a double-masked randomised placebo-controlled trial designed to evaluate the efficacy of a single dose of azithromycin (20 mg/kg) for the prevention of child mortality. Newborns (n=21 712) aged 8-27 days weighing at least 2500 g are 1:1 randomised to a single, directly observed, oral dose of azithromycin or matching placebo. Participants are followed weekly for 3 weeks after treatment to screen for adverse events, including IHPS. The primary outcome is all-cause mortality at the 6-month study visit.Ethics and disseminationThis study was approved by the Institutional Review Boards at the University of California, San Francisco in San Francisco, USA (Protocol #18-25027) and the Comité National d'Ethique pour la Recherche in Ouagadougou, Burkina Faso (Protocol #2018-10-123). The findings of this trial will be presented at local, regional and international meetings and published in open access peer-reviewed journals.Trial registration numberNCT03682653; Pre-results

Anthropometric indices of Gambian children after one or three annual rounds of mass drug administration with azithromycin for trachoma control.

BACKGROUND: Mass drug administration (MDA) with azithromycin, carried out for the control of blinding trachoma, has been linked to reduced mortality in children. While the mechanism behind this reduction is unclear, it may be due, in part, to improved nutritional status via a potential reduction in the community burden of infectious disease. To determine whether MDA with azithromycin improves anthropometric indices at the community level, we measured the heights and weights of children aged 1 to 4 years in communities where one (single MDA arm) or three annual rounds (annual MDA arm) of azithromycin had been distributed. METHODS: Data collection took place three years after treatment in the single MDA arm and one year after the final round of treatment in the annual MDA arm. Mean height-for-age, weight-for-age and weight-for-height z scores were compared between treatment arms. RESULTS: No significant differences in mean height-for-age, weight-for-age or weight-for-height z scores were found between the annual MDA and single MDA arms, nor was there a significant reduction in prevalence of stunting, wasting or underweight between arms. CONCLUSIONS: Our data do not provide evidence that community MDA with azithromycin improved anthropometric outcomes of children in The Gambia. This may suggest reductions in mortality associated with azithromycin MDA are due to a mechanism other than improved nutritional status

Pertussis post-exposure prophylaxis among household contacts: a cost-utility analysis.

BACKGROUND: Recent pertussis outbreaks have prompted re-examination of post-exposure prophylaxis (PEP) strategies, when immunization is not immediately protective. Chemoprophylaxis is recommended to household contacts; however there are concerns of clinical failure and significant adverse events, especially with erythromycin among infants who have the highest disease burden. Newer macrolides offer fewer side effects at higher drug costs. We sought to determine the cost-effectiveness of PEP strategies from the health care payer perspective. METHODS: A Markov model was constructed to examine 4 mutually exclusive strategies: erythromycin, azithromycin, clarithromycin, or no intervention, stratified by age group of contacts ("infant", "child", and "adult"). Transition probabilities, costs and quality-adjusted life years (QALYs) were derived from the literature. Chronic neurologic sequelae were modeled over a lifetime, with costs and QALYs discounted at 5%. Associated health outcomes and costs were compared, and incremental cost-effectiveness ratios (ICER) were calculated in 2012 Canadian dollars. Deterministic and probabilistic sensitivity analyses were performed to evaluate the degree of uncertainty in the results. FINDINGS: Azithromycin offered the highest QALYs in all scenarios. While this was the dominant strategy among infants, it produced an ICER of $16,963 per QALY among children and$2,415 per QALY among adults. Total QALYs with azithromycin were 19.7 for a 5-kg infant, 19.4 for a 10-year-old child, and 18.8 for a 30-year-old adult. The costs of azithromycin PEP among infants, children and adults were $1,976,$132 and $90, respectively. While results were sensitive to changes in PEP effectiveness (11$379 to $59,644), the choice of strategy remained unchanged. INTERPRETATION: Pertussis PEP is a cost-effective strategy compared with no intervention and plays an important role in contact management, potentially in outbreak situations. From a healthcare payer perspective, azithromycin is the optimal strategy among all contact groups

Impact of antiretroviral therapy on adult HIV prevalence in a low-income rural setting in Uganda: a longitudinal population-based study.

OBJECTIVE: To estimate the contribution to HIV prevalence of lives saved due to the introduction of antiretroviral therapy (ART) in rural Uganda in 2004. DESIGN: Open population-based cohort study. METHODS: An open general population cohort with annual demographic and HIV serostatus data is used to estimate annual HIV prevalence, HIV incidence, and mortality from 2000 to 2010. We calculated standardized mortality rates among HIV-positive adults and the expected number of deaths in the cohort if ART had not been available during 2004-2010, based on the average mortality rate in the 4 years (2000-2003) before ART introduction. RESULTS: During 2004-2010, the estimated prevalence increased by 29% from 6.9% to 8.9%. HIV incidence was 5.6 cases per 1000 person-years in 2004, falling to 3.9 cases per 1000 person-years in 2006, and slightly rising to 5.1 in 2010. There was an increase of 182 in the number of HIV-positive participants during that period, cumulatively 228 lives were saved due to ART. Expected lives saved due to ART accounted for an increasing proportion of the estimated HIV prevalence from 4.0% in 2004 to 29.4% in 2010. CONCLUSIONS: Expected lives saved due to ART largely accounted for the increased estimated HIV prevalence from 2004 to 2010. Because HIV prevalence survey results are important for planning, programming, and policy, their interpretation requires consideration of the increasing impact of ART in decreasing mortality

Influence of chronic azithromycin treatment on the composition of the oropharyngeal microbial community in patients with severe asthma

Background: This study of the oropharyngeal microbiome complements the previously published AZIthromycin in Severe ASThma (AZISAST) clinical trial, where the use of azithromycin was assessed in subjects with exacerbationprone severe asthma. Here, we determined the composition of the oropharyngeal microbial community by means of deep sequencing of the amplified 16S rRNA gene in oropharyngeal swabs from patients with exacerbationprone severe asthma, at baseline and during and after 6 months treatment with azithromycin or placebo. Results: A total of 1429 OTUs were observed, of which only 59 were represented by more than 0.02% of the reads. Firmicutes, Bacteroidetes, Fusobacteria, Proteobacteria and Actinobacteria were the most abundant phyla and Streptococcus and Prevotella were the most abundant genera in all the samples. Thirteen species only accounted for two thirds of the reads and two species only, i.e. Prevotella melaninogenica and Streptococcus mitis/pneumoniae, accounted for one fourth of the reads. We found that the overall composition of the oropharyngeal microbiome in patients with severe asthma is comparable to that of the healthy population, confirming the results of previous studies. Long term treatment (6 months) with azithromycin increased the species Streptococcus salivarius approximately 5-fold and decreased the species Leptotrichia wadei approximately 5-fold. This was confirmed by Boruta feature selection, which also indicated a significant decrease of L. buccalis/L. hofstadtii and of Fusobacterium nucleatum. Four of the 8 treated patients regained their initial microbial composition within one month after cessation of treatment. Conclusions: Despite large diversity of the oropharyngeal microbiome, only a few species predominate. We confirm the absence of significant differences between the oropharyngeal microbiomes of people with and without severe asthma. Possibly, long term azithromycin treatment may have long term effects on the composition of the oropharygeal microbiome in half of the patients

Travelers’ diarrhea and other gastrointestinal symptoms among Boston-area international travelers

INTRODUCTION: Travelers' diarrhea (TD) and non-TD gastrointestinal (GI) symptoms are common among international travelers. In a study of short-term travelers from Switzerland to developing countries, the most common symptom experienced was severe diarrhea (8.5%) followed by vomiting or abdominal cramps (4%).1 GI illnesses were the most frequently reported diagnoses (34%) among ill-returned travelers to GeoSentinel clinics.2 Of those returning to U.S. GeoSentinel clinics, acute diarrhea (30%) was the most common diagnosis.3 In one cohort of U.S. travelers, 46% reported diarrhea.4 GI illnesses can last from 2 days to weeks or longer,5 disrupting plans during travel or after returning home. Eighty percent of those who experienced diarrhea during travel treated themselves with medication and 6% sought medical care. METHODS: The Boston Area Travel Medicine Network (BATMN) is a research collaboration of travel clinics in the greater Boston area representing urban-, suburban-, academic-, and university-affiliated facilities. A convenience sample of travelers ≥ 18 years of age attending three BATMN clinics between 2009 and 2011 for pre-travel consultations completed pre-travel surveys, at least one survey weekly during travel, and a post-travel survey 2–4 weeks after return. Travelers were asked to complete a survey at the end of each week of their trip. Institutional review board approvals were obtained at all sites and the Centers for Disease Control and Prevention, and participants provided written informed consent. Information collected included demographic and trip characteristics, vaccines and medications recommended/prescribed before travel, medications taken during travel, dietary practices during travel (consumption of tap water, ice in drinks, unpasteurized dairy products, and salads), symptoms experienced, and impact of illness during and after travel. Vaccinations, prescriptions, and travel health advice given during the pre-travel consultation were recorded by a clinician, and the remainder of the surveys were completed by the traveler. Data were entered into a password-protected database (CS Pro, U.S. Census Bureau, Washington, DC). RESULTS: We enrolled 987 travelers; 628 (64%) completed all three parts (pre-, during, and post-travel) and were included in the study. Comparison of the 628 to the 359 who did not complete all three parts (noncompleters) revealed no differences, except that completion rates were higher for white travelers than all other racial/ethnic groups (P < 0.001) and for older travelers (median age 47 years versus 32 years in noncompleters, P < 0.001).11 Of those 628 travelers, 208 (33%) experienced TD, 45 (7%) experienced non-TD GI symptoms, 147 (23%) experienced non-GI symptoms, and 228 (36%) did not experience any symptoms during or after travel. Of the 208 with TD, 140 (67%) reported diarrhea as their only symptom, whereas 33 (16%) also experienced nausea/vomiting, 23 (11%) abdominal pain, and 27 (13%) fever (Table 1). Of the 45 who reported non-TD GI symptoms, 21 (47%) experienced nausea/vomiting, 19 (42%) experienced constipation, and 10 (22%) experienced abdominal pain during or after travel (Table 2). Almost all travelers (99%) received advice about food and water precautions and diarrhea management during pre-travel consultation