@article {151, title = {High-throughput sequencing of pooled samples to determine community-level microbiome diversity.}, journal = {Ann Epidemiol}, volume = {39}, year = {2019}, month = {2019 11}, pages = {63-68}, abstract = {

PURPOSE: Community-level interventions in cluster randomized controlled trials may alter the gut microbiome of individuals. The current method of estimating community diversities uses microbiome data obtained from multiple individual{\textquoteright}s specimens. Here we propose randomly pooling a number of microbiome samples from the same community into one sample before sequencing to estimate community-level microbiome diversity.

METHODS: We design and analyze an experiment to compare community microbiome diversity (gamma-diversity) estimates derived from 16S rRNA gene sequencing of 1) individually sequenced specimens vs. 2) pooled specimens collected from a community. Pool sizes of 10, 20, and 40 are considered. We then compare the gamma-estimates using Pearson{\textquoteright}s correlation as well as using Bland and Altman agreement analysis for three established diversity indices including richness, Simpson{\textquoteright}s and Shannon{\textquoteright}s.

RESULTS: The gamma-diversity estimates are highly correlated, with most being statistically significant. All correlations between all three diversity estimates are significant in the 10-pooled data. Pools comprising 40 specimens are closest to the line of agreement, but all pooled samples and individual samples fall within the 95\% limits of agreement.

CONCLUSIONS: Pooling microbiome samples before DNA amplification and metagenomics sequencing to estimate community-level diversity is a viable measure to consider in population-level association research studies.

}, keywords = {Administration, Oral, Anti-Bacterial Agents, Azithromycin, Bacteria, Biodiversity, Child, Preschool, Female, Gastrointestinal Microbiome, Gastrointestinal Tract, High-Throughput Nucleotide Sequencing, Humans, Infant, Infant, Newborn, Male, Metagenomics, Microbiota, Niger, Placebos, RNA, Ribosomal, 16S, Sequence Analysis, DNA}, issn = {1873-2585}, doi = {10.1016/j.annepidem.2019.09.002}, author = {Ray, Kathryn J and Cotter, Sun Y and Arzika, Ahmed M and Kim, Jessica and Boubacar, Nameywa and Zhou, Zhaoxia and Zhong, Lina and Porco, Travis C and Keenan, Jeremy D and Lietman, Thomas M and Doan, Thuy} } @article {121, title = {Longer-Term Assessment of Azithromycin for Reducing Childhood Mortality in Africa.}, journal = {N Engl J Med}, volume = {380}, year = {2019}, month = {2019 Jun 06}, pages = {2207-2214}, abstract = {

BACKGROUND: The MORDOR I trial (Macrolides Oraux pour R{\'e}duire les D{\'e}c{\`e}s avec un Oeil sur la R{\'e}sistance) showed that in Niger, mass administration of azithromycin twice a year for 2 years resulted in 18\% lower postneonatal childhood mortality than administration of placebo. Whether this benefit could increase with each administration or wane owing to antibiotic resistance was unknown.

METHODS: In the Niger component of the MORDOR I trial, we randomly assigned 594 communities to four twice-yearly distributions of either azithromycin or placebo to children 1 to 59 months of age. In MORDOR II, all these communities received two additional open-label azithromycin distributions. All-cause mortality was assessed twice yearly by census workers who were unaware of participants{\textquoteright} original assignments.

RESULTS: In the MORDOR II trial, the mean ({\textpm}SD) azithromycin coverage was 91.3{\textpm}7.2\% in the communities that received twice-yearly azithromycin for the first time (i.e., had received placebo for 2 years in MORDOR I) and 92.0{\textpm}6.6\% in communities that received azithromycin for the third year (i.e., had received azithromycin for 2 years in MORDOR I). In MORDOR II, mortality was 24.0 per 1000 person-years (95\% confidence interval [CI], 22.1 to 26.3) in communities that had originally received placebo in the first year and 23.3 per 1000 person-years (95\% CI, 21.4 to 25.5) in those that had originally received azithromycin in the first year, with no significant difference between groups (P = 0.55). In communities that had originally received placebo, mortality decreased by 13.3\% (95\% CI, 5.8 to 20.2) when the communities received azithromycin (P = 0.007). In communities that had originally received azithromycin and continued receiving it for an additional year, the difference in mortality between the third year and the first 2 years was not significant (-3.6\%; 95\% CI, -12.3 to 4.5; P = 0.50).

CONCLUSIONS: We found no evidence that the effect of mass administration of azithromycin on childhood mortality in Niger waned in the third year of treatment. Childhood mortality decreased when communities that had originally received placebo received azithromycin. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT02047981.).

}, keywords = {Anti-Bacterial Agents, Azithromycin, Child Mortality, Child, Preschool, Drug Administration Schedule, Female, Humans, Infant, Infant Mortality, Male, Mass Drug Administration, Niger}, issn = {1533-4406}, doi = {10.1056/NEJMoa1817213}, author = {Keenan, Jeremy D and Arzika, Ahmed M and Maliki, Ramatou and Boubacar, Nameywa and Elh Adamou, Sanoussi and Moussa Ali, Maria and Cook, Catherine and Lebas, Elodie and Lin, Ying and Ray, Kathryn J and O{\textquoteright}Brien, Kieran S and Doan, Thuy and Oldenburg, Catherine E and Callahan, E Kelly and Emerson, Paul M and Porco, Travis C and Lietman, Thomas M} }