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Mass azithromycin distribution reduces all-cause childhood mortality in some high-mortality settings in sub-Saharan Africa. Although the greatest benefits have been shown in children 1 to 5 months old living in areas with high mortality rates, no evidence of a benefit was found of neonatal azithromycin in a low-mortality setting on mortality at 6 months. We conducted a 1:1 randomized, placebo-controlled trial evaluating the effect of a single oral 20-mg/kg dose of azithromycin or matching placebo administered during the neonatal period on all-cause and cause-specific infant mortality at 12 months of age in five regions of Burkina Faso. Neonates were eligible if they were between the ages of 8 and 27 days and weighed at least 2,500 g at enrollment. Cause of death was determined via the WHO 2016 verbal autopsy tool. We compared all-cause and cause-specific mortality using binomial regression. Of 21,832 infants enrolled in the study, 116 died by 12 months of age. There was no significant difference in all-cause mortality between the azithromycin and placebo groups (azithromycin: 52 deaths, 0.5%; placebo, 64 deaths, 0.7%; hazard ratio, 0.81; 95% CI, 0.56–1.17; P = 0.30). There was no evidence of a difference in the distribution of causes of death (P = 0.40) and no significant difference in any specific cause of death between groups. Mortality rates were low at 12 months of age, and there was no evidence of an effect of neonatal azithromycin on all-cause or cause-specific mortality.

Observational studies have linked early-life antibiotic exposure to increased risk of obesity in children in high income settings. We evaluated whether neonatal antibiotic exposure led to changes in infant growth at 6 months of age in Burkina Faso. Neonates aged 8 to 27 days of age who weighed at least 2,500 g at the time of enrollment were randomized in a 1:1 fashion to a single oral 20-mg/kg dose of azithromycin or equivalent volume of placebo from April 2019 through December 2020. Weight, length, and mid-upper-arm circumference (MUAC) were measured at baseline and 6 months of age. Growth outcomes, including weight gain in grams per day, length change in millimeters per day, and changes in weight-for-age Z-score (WAZ), weight-for-length Z-score (WLZ), length-for-age Z-score (LAZ), and MUAC were compared among neonates randomized to azithromycin compared with placebo. Among 21,832 neonates enrolled in the trial, median age at enrollment was 11 days, and 50% were female. We found no evidence of a difference in weight gain (mean difference −0.009 g/day, 95% confidence interval [CI]: −0.16 to 0.14, P = 0.90), length change (mean difference 0.003 mm/day, 95% CI: −0.002 to 0.007, P = 0.23), or WAZ (mean difference −0.005 SD, 95% CI: −0.03 to 0.02, P = 0.72), WLZ (mean difference −0.01 SD, 95% CI: −0.05 to 0.02, P = 0.39), LAZ (mean difference 0.01, 95% CI: −0.02 to 0.04, P = 0.47), or MUAC (mean difference 0.01 cm, 95% CI: −0.02 to 0.04, P = 0.49). These results do not suggest that azithromycin has growth-promoting properties in infants when administered during the neonatal period. Trial registration: ClinicalTrials.gov NCT03682653.

We evaluated antibiotic resistance selection in Streptococcus pneumoniae isolates from children participating in an individually randomized trial of single-dose azithromycin versus placebo. After 14 days, the prevalence of resistance to erythromycin, oxacillin, and clindamycin was elevated in the azithromycin versus placebo group. There was no difference at 6 months.

While effective for slowing the transmission of SARS-CoV-2, public health measures, such as physical distancing and stay-at-home orders, have significantly shifted the way people interact and maintain social connections. To better understand how people sought social and psychological support amid the pandemic, we conducted a longitudinal qualitative evaluation of participants enrolled in a COVID-19 treatment trial (N = 30). All participants from the parent trial who consented to being contacted for future research studies were recruited electronically via email, and first-round virtual interviews were conducted between December 2020 and March 2021. Participants who participated in first-round interviews were contacted again, and follow-up interviews were conducted in January–February 2022. The results reported significant shifts in how participants connected to social support, including changes from physical to virtual modalities, and using different social networks for distinct purposes (i.e., Reddit/Facebook for information, WhatsApp for community connection). While having COVID-19, profound loneliness during isolation was described; yet, to mitigate effects, virtual support (i.e., emotional, knowledge-seeking) as well as in-person material support (e.g., groceries, snow-shoveling), were key. Public health efforts are needed to develop interventions that will improve the narratives about mental health challenges related to COVID-19 isolation, and to provide opportunities to share challenges in a supportive manner among social networks. Supporting social cohesion, despite the everchanging nature of COVID-19, will necessitate innovative multimodal strategies that learn from lived experiences across various stages of the pandemic.

Biannual mass azithromycin administration reduces all-cause childhood mortality in some sub-Saharan African settings, with the largest effects in children aged 1-5 months. Azithromycin has not been distributed to children1 month due to risk of infantile hypertrophic pyloric stenosis (IHPS).This 1:1 placebo-controlled trial, randomized neonates aged 8-27 days to a single oral dose of azithromycin (20 mg/kg) or equivalent volume of placebo in 5 regions of Burkina Faso during 2019 and 2020. The primary outcome was all-cause mortality at 6 months of age. Infants were evaluated at 21 days after treatment and at 3 and 6 months of age for vital status; family and provider surveillance for IHPS continued throughout.Of 21,832 enrolled neonates, 10,898 were allocated to azithromycin and 10,934 to placebo. At 6 months of age, 92 infants had died, 42 (0.44%) in the azithromycin group and 50 (0.52%) in the placebo group (hazard ratio 0.85, 95% confidence interval 0.56 to 1.28,Overall mortality was lower than anticipated when the trial was designed, thus limiting its power. The available data do not support the routine use of azithromycin for prevention of mortality in neonates in sub-Saharan African settings similar to the one in which this trial was conducted.ClinicalTrials.gov NCT03682653.

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.

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 analysisTheNouveaux-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.

The persistence of latently HIV-infected cellular reservoirs represents the major obstacle to virus eradication in patients under antiretroviral therapy (ART). Cure strategies to eliminate these reservoirs are thus needed to reactivate proviral gene expression in latently infected cells. In this study, we tested optimal concentrations of PKC agonist candidates (PEP005/Ingenol-3-angelate, prostratin, bryostatin-1, and JQ1) to reactivate HIV latency in vitro, and examined their effects on cell survival, activation and epigenetic histone methylation after treatment alone or in combination in cell line and isolated CD4 T cells from SIV-infected macaques. The results showed that PKC agonists increased cell activation with different degrees of latency reactivation, concomitant with reduced levels of histone methylation. With increasing concentrations, prostratin and byrostain-1 treatment rapidly reduced cell survival and cell activation. The PKC agonist combinations, or in combination with JQ1, led to modest levels of synergistic reactivation of HIV. Remarkably, PEP005 treatment alone caused marked reactivation of HIV latency, similar to PMA stimulation. These findings suggested that PEP005 alone, as indicated its lower cytotoxicity and lower effective dose inducing maximal reactivation, might be a candidate for effectively reactivating HIV latency as part of a therapeutic strategy for HIV infection.