25 results on '"Ramatou Maliki"'
Search Results
2. Monitoring transmission intensity of trachoma with serology
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Christine Tedijanto, Anthony W. Solomon, Diana L. Martin, Scott D. Nash, Jeremy D. Keenan, Thomas M. Lietman, Patrick J. Lammie, Kristen Aiemjoy, Abdou Amza, Solomon Aragie, Ahmed M. Arzika, E. Kelly Callahan, Sydney Carolan, Adisu Abebe Dawed, E. Brook Goodhew, Sarah Gwyn, Jaouad Hammou, Boubacar Kadri, Khumbo Kalua, Ramatou Maliki, Beido Nassirou, Fikre Seife, Zerihun Tadesse, Sheila K. West, Dionna M. Wittberg, Taye Zeru Tadege, and Benjamin F. Arnold
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Science - Abstract
Abstract Trachoma, caused by ocular Chlamydia trachomatis infection, is targeted for global elimination as a public health problem by 2030. To provide evidence for use of antibodies to monitor C. trachomatis transmission, we collated IgG responses to Pgp3 antigen, PCR positivity, and clinical observations from 19,811 children aged 1–9 years in 14 populations. We demonstrate that age-seroprevalence curves consistently shift along a gradient of transmission intensity: rising steeply in populations with high levels of infection and active trachoma and becoming flat in populations near elimination. Seroprevalence (range: 0–54%) and seroconversion rates (range: 0–15 per 100 person-years) correlate with PCR prevalence (r: 0.87, 95% CI: 0.57, 0.97). A seroprevalence threshold of 13.5% (seroconversion rate 2.75 per 100 person-years) identifies clusters with any PCR-identified infection at high sensitivity ( >90%) and moderate specificity (69–75%). Antibody responses in young children provide a robust, generalizable approach to monitor population progress toward and beyond trachoma elimination.
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- 2023
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3. Effect of biannual azithromycin distribution on antibody responses to malaria, bacterial, and protozoan pathogens in Niger
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Ahmed M. Arzika, Ramatou Maliki, E. Brook Goodhew, Eric Rogier, Jeffrey W. Priest, Elodie Lebas, Kieran S. O’Brien, Victoria Le, Catherine E. Oldenburg, Thuy Doan, Travis C. Porco, Jeremy D. Keenan, Thomas M. Lietman, Diana L. Martin, Benjamin F. Arnold, and MORDOR-Niger Study Group
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Science - Abstract
In a randomized placebo-controlled trial in rural Niger, biannual azithromycin distribution to children 1-59 months reduced all-cause mortality. Based on serology, Arzika et al. here report a reduction of Campylobacter infection, supporting one mechanism for the intervention’s impact on mortality.
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- 2022
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4. Comparison of door-to-door and fixed-point delivery of azithromycin distribution for child survival in Niger: A cluster-randomized trial.
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Ahmed M Arzika, Ramatou Maliki, Abdou Amza, Alio Karamba, Nasser Gallo, Bawa Aichatou, Ismael Issa Sara, Diallo Beidi, Laminou Maliki Haroun, Farissatou Oumarou, Elodie Lebas, Brittany Peterson, Emily Colby, William Nguyen, Zijun Liu, Meagan C Fitzpatrick, Benjamin F Arnold, Thomas M Lietman, Kieran S O'Brien, and AVENIR Study Group
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Public aspects of medicine ,RA1-1270 - Abstract
Recent evidence indicates mass azithromycin distribution reduces under-5 mortality. This intervention is being considered for child survival programs in high mortality sub-Saharan African settings. The delivery approach used in prior studies required a full-time census and distribution team, which is not feasible for most programs. To determine the optimal programmatic approach to delivery, this study aimed to compare treatment coverage, costs, and acceptability of different delivery approaches with existing community health workers (CHWs). This cluster-randomized trial included rural and peri-urban communities in Dosso, Niger (clinicaltrials.gov, NCT04774991). A random sample of 80 eligible communities was randomized 1:1 to biannual door-to-door or fixed-point delivery of oral azithromycin to children 1-59 months old over 1 year. Data analysts alone were masked given the nature of the intervention. The primary outcome was community-level treatment coverage defined as the number of children treated recorded by CHWs divided by the number of eligible children determined using a post-distribution census. Costs were monitored through routine administrative data collection and micro-costing. The census included survey questions on intervention acceptability among caregivers, community leaders, and CHWs. After randomization, 1 community was excluded due to inaccuracies in available administrative data, resulting in 39 communities receiving door-to-door delivery. At the second distribution, community-level mean treatment coverage was 105% (SD 44%) in the door-to-door arm and 92% (SD 20%) in the fixed-point arm (Mean difference 13%, 95% CI -2% to 28%, P-value = 0.08). The total cost per dose delivered was $1.91 in the door-to-door arm and $2.51 in the fixed-point arm. Indicators of acceptability were similar across stakeholder groups in both arms, with most respondents in each group indicating a preference for door-to-door. Overall, door-to-door delivery is the preferred approach to azithromycin distribution in this setting and might reach more children at a lower cost per dose delivered than fixed-point. Trial Registration: clinicaltrials.gov NCT04774991.
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- 2023
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5. Simplified dosing of oral azithromycin for children 1–11 months old in child survival programmes: age-based and height-based dosing protocols
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Catherine E Oldenburg, Thomas M Lietman, Ali Sie, Kieran S O'Brien, Elodie Lebas, Mamadou Bountogo, Jessica Brogdon, Valentin Boudo, Amza Abdou, Paul Emerson, Huiyu Hu, Ahmed Mamane Arzika, Ramatou Maliki, Alio Karamba Mankara, Mamadou Outtara, Fanny Yago-Wienne, Issouf Bamba, Charles Knirsch, PJ Hooper, and Fanice Nyatigo
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Medicine (General) ,R5-920 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Background To 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.Methods This 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.Results The 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.Conclusions Overall, 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.
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- 2022
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6. Age-based targeting of biannual azithromycin distribution for child survival in Niger: an adaptive cluster-randomized trial protocol (AVENIR)
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Kieran S. O’Brien, Ahmed M. Arzika, Abdou Amza, Ramatou Maliki, Sani Ousmane, Boubacar Kadri, Beido Nassirou, Alio Karamba Mankara, Abdoul Naser Harouna, Emily Colby, Elodie Lebas, Zijun Liu, Victoria Le, William Nguyen, Jeremy D. Keenan, Catherine E. Oldenburg, Travis C. Porco, Thuy Doan, Benjamin F. Arnold, Thomas M. Lietman, and the AVENIR Study Group
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Azithromycin ,Mortality ,Cluster-randomized trial ,Adaptive trial ,Mass drug administration ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Biannual distribution of azithromycin to children 1–59 months old reduced mortality by 14% in a cluster-randomized trial. The World Health Organization has proposed targeting this intervention to the subgroup of children 1–11 months old to reduce selection for antimicrobial resistance. Here, we describe a trial designed to determine the impact of age-based targeting of biannual azithromycin on mortality and antimicrobial resistance. Methods AVENIR is a cluster-randomized, placebo-controlled, double-masked, response-adaptive large simple trial in Niger. During the 2.5-year study period, 3350 communities are targeted for enrollment. In the first year, communities in the Dosso region will be randomized 1:1:1 to 1) azithromycin 1–11: biannual azithromycin to children 1–11 months old with placebo to children 12–59 months old, 2) azithromycin 1–59: biannual azithromycin to children 1–59 months old, or 3) placebo: biannual placebo to children 1–59 months old. Regions enrolled after the first year will be randomized with an updated allocation based on the probability of mortality in children 1–59 months in each arm during the preceding study period. A biannual door-to-door census will be conducted to enumerate the population, distribute azithromycin and placebo, and monitor vital status. Primary mortality outcomes are defined as all-cause mortality rate (deaths per 1000 person-years) after 2.5 years from the first enrollment in 1) children 1–59 months old comparing the azithromycin 1–59 and placebo arms, 2) children 1–11 months old comparing the azithromycin 1–11 and placebo arm, and 3) children 12–59 months in the azithromycin 1–11 and azithromycin 1–59 arms. In the Dosso region, 50 communities from each arm will be followed to monitor antimicrobial resistance. Primary resistance outcomes will be assessed after 2 years of distributions and include 1) prevalence of genetic determinants of macrolide resistance in nasopharyngeal samples from children 1–59 months old, and 2) load of genetic determinants of macrolide resistance in rectal samples from children 1–59 months old. Discussion As high-mortality settings consider this intervention, the results of this trial will provide evidence to support programmatic and policy decision-making on age-based strategies for azithromycin distribution to promote child survival. Trial registration This trial was registered on January 13, 2020 (clinicaltrials.gov: NCT04224987 ).
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- 2021
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7. Cause-specific mortality of children younger than 5 years in communities receiving biannual mass azithromycin treatment in Niger: verbal autopsy results from a cluster-randomised controlled trial
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Jeremy D Keenan, ProfMD, Ahmed M Arzika, MPH, Ramatou Maliki, MPH, Sanoussi Elh Adamou, MD, Fatima Ibrahim, RN, Mariama Kiemago, RN, Nana Fatima Galo, RN, Elodie Lebas, RN, Catherine Cook, MPH, Benjamin Vanderschelden, BSc, Robin L Bailey, ProfBM, Sheila K West, ProfPhD, Travis C Porco, ProfPhD, Thomas M Lietman, ProfMD, Paul M Emerson, Jerusha Weaver, Sheila K West, Robin L Bailey, John Hart, Amza Abdou, Boubacar Kadri, Nassirou Beido, E Kelly Callahan, Aisha E Stewart, Ahmed M Arzika, Sanoussi Elh Adamou, Nana Fatima Galo, Fatima Ibrahim, Salissou Kane, Mariama Kiemago, Ramatou Maliki, Catherine Cook, Sun Y Cotter, Thuy Doan, Dionna M Fry, Jeremy D Keenan, Elodie Lebas, Thomas M Lietman, Ying Lin, Kieran S O'Brien, Catherine E Oldenburg, Travis C Porco, Kathryn J Ray, Philip J Rosenthal, George W Rutherford, Benjamin Vanderschelden, Nicole E Varnado, Lina Zhong, and Zhaoxia Zhou
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Public aspects of medicine ,RA1-1270 - Abstract
Summary: Background: The Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) trial found that biannual mass distribution of azithromycin to children younger than 5 years in Niger reduced the primary outcome of all-cause mortality by 18%. We aimed to determine the causes of mortality among deceased children using verbal autopsy. Methods: In this 2-year cluster-randomised controlled trial, 594 community clusters in Niger were randomly allocated (1:1 ratio) to receive biannual mass distributions of either oral azithromycin (approximately 20 mg per kg of bodyweight) or placebo targeted to children aged 1–59 months. Participants, study investigators, and field workers were masked to treatment allocation. Between Nov 23, 2014, and July 31, 2017, 3615 child deaths were recorded by use of biannual house-to-house censuses, and verbal autopsies were done between May 26, 2015, and May 17, 2018, to identify cause of death. Cause-specific mortality, as assessed by verbal autopsy, was a prespecified secondary outcome. This trial is completed and is registered with ClinicalTrials.gov, NCT02047981. Findings: Between Nov 23, 2014, and July 31, 2017, 303 communities (n=40 375 children at baseline) in Niger received mass azithromycin and 291 communities (n=35 747 children at baseline) received placebo. Treatment coverage was 90·3% (SD 10·6) in the azithromycin group and 90·4% (10·1) in the placebo group. No communities were lost to follow-up. In total, 1727 child deaths in the azithromycin group and 1888 child deaths in the placebo group were reported from the population censuses. Of these, the cause of death for 1566 (90·7%) children in the azithromycin group and 1735 (91·9%) children in the placebo group were ascertained by verbal autopsy interviews. In the azithromycin group, 437 (27·9%) deaths were due to malaria, 252 (16·1%) deaths were due to pneumonia, and 234 (14·9%) deaths were due to diarrhoea. In the placebo group, 493 (28·4%) deaths were due to malaria, 275 (15·9%) deaths were due to pneumonia, and 251 (14·5%) deaths were due to diarrhoea. Relative to communities that received placebo, child mortality in communities that received azithromycin was lower for malaria (incidence rate ratio 0·78, 95% CI 0·66–0·92; p=0·0029), dysentery (0·65, 0·44–0·94; p=0·025), meningitis (0·67, 0·46–0·97; p=0·036), and pneumonia (0·83, 0·68–1·00; p=0·051). The distribution of causes of death did not differ significantly between the two study groups (p=0·98). Interpretation: Mass azithromycin distribution resulted in approximately a third fewer deaths in children aged 1–59 months due to meningitis and dysentery, and a fifth fewer deaths due to malaria and pneumonia. The lack of difference in the distribution of causes of death between the azithromycin and placebo groups could be attributable to the broad spectrum of azithromycin activity and the study setting, in which most childhood deaths were due to infections. Funding: Bill & Melinda Gates Foundation.
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- 2020
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8. Biannual azithromycin distribution and child mortality among malnourished children: A subgroup analysis of the MORDOR cluster-randomized trial in Niger.
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Kieran S O'Brien, Ahmed M Arzika, Ramatou Maliki, Farouk Manzo, Alio K Mamkara, Elodie Lebas, Catherine Cook, Robin L Bailey, Sheila K West, Catherine E Oldenburg, Travis C Porco, Benjamin Arnold, Jeremy D Keenan, Thomas M Lietman, and MORDOR Study Group
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Medicine - Abstract
BackgroundBiannual azithromycin distribution has been shown to reduce child mortality as well as increase antimicrobial resistance. Targeting distributions to vulnerable subgroups such as malnourished children is one approach to reaching those at the highest risk of mortality while limiting selection for resistance. The objective of this analysis was to assess whether the effect of azithromycin on mortality differs by nutritional status.Methods and findingsA large simple trial randomized communities in Niger to receive biannual distributions of azithromycin or placebo to children 1-59 months old over a 2-year timeframe. In exploratory subgroup analyses, the effect of azithromycin distribution on child mortality was assessed for underweight subgroups using weight-for-age Z-score (WAZ) thresholds of -2 and -3. Modification of the effect of azithromycin on mortality by underweight status was examined on the additive and multiplicative scale. Between December 2014 and August 2017, 27,222 children 1-11 months of age from 593 communities had weight measured at their first study visit. Overall, the average age among included children was 4.7 months (interquartile range [IQR] 3-6), 49.5% were female, 23% had a WAZ < -2, and 10% had a WAZ < -3. This analysis included 523 deaths in communities assigned to azithromycin and 661 deaths in communities assigned to placebo. The mortality rate was lower in communities assigned to azithromycin than placebo overall, with larger reductions among children with lower WAZ: -12.6 deaths per 1,000 person-years (95% CI -18.5 to -6.9, P < 0.001) overall, -17.0 (95% CI -28.0 to -7.0, P = 0.001) among children with WAZ < -2, and -25.6 (95% CI -42.6 to -9.6, P = 0.003) among children with WAZ < -3. No statistically significant evidence of effect modification was demonstrated by WAZ subgroup on either the additive or multiplicative scale (WAZ < -2, additive: 95% CI -6.4 to 16.8, P = 0.34; WAZ < -2, multiplicative: 95% CI 0.8 to 1.4, P = 0.50, WAZ < -3, additive: 95% CI -2.2 to 31.1, P = 0.14; WAZ < -3, multiplicative: 95% CI 0.9 to 1.7, P = 0.26). The estimated number of deaths averted with azithromycin was 388 (95% CI 214 to 574) overall, 116 (95% CI 48 to 192) among children with WAZ < -2, and 76 (95% CI 27 to 127) among children with WAZ < -3. Limitations include the availability of a single weight measurement on only the youngest children and the lack of power to detect small effect sizes with this rare outcome. Despite the trial's large size, formal tests for effect modification did not reach statistical significance at the 95% confidence level.ConclusionsAlthough mortality rates were higher in the underweight subgroups, this study was unable to demonstrate that nutritional status modified the effect of biannual azithromycin distribution on mortality. Even if the effect were greater among underweight children, a nontargeted intervention would result in the greatest absolute number of deaths averted.Trial registrationThe MORDOR trial is registered at clinicaltrials.gov NCT02047981.
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- 2020
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9. Biannual mass azithromycin distributions and malaria parasitemia in pre-school children in Niger: A cluster-randomized, placebo-controlled trial.
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Ahmed M Arzika, Ramatou Maliki, Nameywa Boubacar, Salissou Kane, Sun Y Cotter, Elodie Lebas, Catherine Cook, Robin L Bailey, Sheila K West, Philip J Rosenthal, Travis C Porco, Thomas M Lietman, Jeremy D Keenan, and MORDOR Study Group
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Medicine - Abstract
BackgroundMass azithromycin distributions have been shown to reduce mortality in preschool children, although the factors mediating this mortality reduction are not clear. This study was performed to determine whether mass distribution of azithromycin, which has modest antimalarial activity, reduces the community burden of malaria.Methods and findingsIn a cluster-randomized trial conducted from 23 November 2014 until 31 July 2017, 30 rural communities in Niger were randomized to 2 years of biannual mass distributions of either azithromycin (20 mg/kg oral suspension) or placebo to children aged 1 to 59 months. Participants, field staff, and investigators were masked to treatment allocation. The primary malaria outcome was the community prevalence of parasitemia on thick blood smear, assessed in a random sample of children from each community at study visits 12 and 24 months after randomization. Analyses were performed in an intention-to-treat fashion. At the baseline visit, a total of 1,695 children were enumerated in the 15 azithromycin communities, and 3,029 children were enumerated in the 15 placebo communities. No communities were lost to follow-up. The mean prevalence of malaria parasitemia at baseline was 8.9% (95% CI 5.1%-15.7%; 52 of 552 children across all communities) in the azithromycin-treated group and 6.7% (95% CI 4.0%-12.6%; 36 of 542 children across all communities) in the placebo-treated group. In the prespecified primary analysis, parasitemia was lower in the azithromycin-treated group at month 12 (mean prevalence 8.8%, 95% CI 5.1%-14.3%; 51 of 551 children across all communities) and month 24 (mean 3.5%, 95% CI 1.9%-5.5%; 21 of 567 children across all communities) than it was in the placebo-treated group at month 12 (mean 15.3%, 95% CI 10.8%-20.6%; 81 of 548 children across all communities) and month 24 (mean 4.8%, 95% CI 3.3%-6.4%; 28 of 592 children across all communities) (P = 0.02). Communities treated with azithromycin had approximately half the odds of parasitemia compared to those treated with placebo (odds ratio [OR] 0.54, 95% CI 0.30 to 0.97). Parasite density was lower in the azithromycin group than the placebo group at 12 and 24 months (square root-transformed outcome; density estimates were 7,540 parasites/μl lower [95% CI -350 to -12,550 parasites/μl; P = 0.02] at a mean parasite density of 17,000, as was observed in the placebo arm). No significant difference in hemoglobin was observed between the 2 treatment groups at 12 and 24 months (mean 0.34 g/dL higher in the azithromycin arm, 95% CI -0.06 to 0.75 g/dL; P = 0.10). No serious adverse events were reported in either group, and among children aged 1 to 5 months, the most commonly reported nonserious adverse events (i.e., diarrhea, vomiting, and rash) were less common in the azithromycin-treated communities. Limitations of the trial include the timing of the treatments and monitoring visits, both of which took place before the peak malaria season, as well as the uncertain generalizability to areas with different malaria transmission dynamics.ConclusionsMass azithromycin distributions were associated with a reduced prevalence of malaria parasitemia in this trial, suggesting one possible mechanism for the mortality benefit observed with this intervention.Trial registrationThe trial was registered on ClinicalTrials.gov (NCT02048007).
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- 2019
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10. Safety of azithromycin in infants under six months of age in Niger: A community randomized trial.
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Catherine E Oldenburg, Ahmed M Arzika, Ramatou Maliki, Mohamed Salissou Kane, Elodie Lebas, Kathryn J Ray, Catherine Cook, Sun Y Cotter, Zhaoxia Zhou, Sheila K West, Robin Bailey, Travis C Porco, Jeremy D Keenan, Thomas M Lietman, and MORDOR Study Group
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
BACKGROUND:Mass azithromycin distribution reduces under-5 child mortality. Trachoma control programs currently treat infants aged 6 months and older. Here, we report findings from an infant adverse event survey in 1-5 month olds who received azithromycin as part of a large community-randomized trial in Niger. METHODS AND PRINCIPAL FINDINGS:Active surveillance of infants aged 1-5 months at the time of treatment was conducted in 30 randomly selected communities from within a large cluster randomized trial of biannual mass azithromycin distribution compared to placebo to assess the potential impact on child mortality. We compared the distribution of adverse events reported after treatment among azithromycin-treated versus placebo-treated infants. From January 2015 to February 2018, the caregivers of 1,712 infants were surveyed. Approximately one-third of caregivers reported at least one adverse event (azithromycin: 29.6%, placebo: 34.3%, risk ratio [RR] 0.86, 95% confidence interval [CI] 0.68 to 1.10, P = 0.23). The most commonly reported adverse events included diarrhea (azithromycin: 19.3%, placebo: 28.1%, RR 0.68, 95% CI 0.49 to 0.96, P = 0.03), vomiting (azithromycin: 15.9%, placebo: 21.0%, RR 0.76, 95% CI 0.56 to 1.02, P = 0.07), and skin rash (azithromycin: 12.3%, placebo: 13.6%, RR 0.90, 95% CI 0.59 to 1.37, P = 0.63). No cases of infantile hypertrophic pyloric stenosis were reported. CONCLUSIONS:Azithromycin given to infants aged 1-5 months appeared to be safe. Inclusion of younger infants in larger azithromycin-based child mortality or trachoma control programs could be considered if deemed effective. TRIAL REGISTRATION:ClinicalTrials.gov NCT02048007.
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- 2018
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11. Impact of Biannual Mass Azithromycin Treatment on Enteropathogen Carriage in Children <5 Years Old in Niger
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James A, Platts-Mills, Elias G, Ayoub, Jixian, Zhang, Elizabeth T Rogawski, McQuade, Ahmed M, Arzika, Ramatou, Maliki, Amza, Abdou, Jeremy D, Keenan, Thomas M, Lietman, Jie, Liu, and Eric R, Houpt
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Microbiology (medical) ,Infectious Diseases ,Child, Preschool ,education ,Prevalence ,Humans ,Infant ,Mass Drug Administration ,Niger ,Azithromycin ,Child ,Anti-Bacterial Agents - Abstract
We analyzed samples obtained at baseline and 24 months in a mass azithromycin administration trial in Niger using quantitative polymerase chain reaction. In villages randomized to azithromycin, Shigella was the only pathogen reduced at 24 months (prevalence ratio, 0.36 [95% confidence interval: .17–.79]; difference in log quantity, −.42 [−.75 to −.10]).
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- 2022
12. Effect of Biannual Mass Azithromycin Distributions to Preschool-Aged Children on Trachoma Prevalence in Niger: A Cluster Randomized Clinical Trial
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Ahmed M, Arzika, Dallas, Mindo-Panusis, Amza, Abdou, Boubacar, Kadri, Beido, Nassirou, Ramatou, Maliki, Amer F, Alsoudi, Tianyi, Zhang, Sun Y, Cotter, Elodie, Lebas, Kieran S, O'Brien, E Kelly, Callahan, Robin L, Bailey, Sheila K, West, E Brook, Goodhew, Diana L, Martin, Benjamin F, Arnold, Travis C, Porco, Thomas M, Lietman, Jeremy D, Keenan, and Zhaoxia, Zhou
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Adult ,Inflammation ,Male ,Trachoma ,Infant, Newborn ,Chlamydia trachomatis ,Azithromycin ,Infant, Newborn, Diseases ,Anti-Bacterial Agents ,Gonorrhea ,Seroepidemiologic Studies ,Child, Preschool ,Prevalence ,Humans ,Niger ,Child - Abstract
Because transmission of ocular strains of Chlamydia trachomatis is 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.To determine the efficacy of mass azithromycin distributions to preschool-aged children as a strategy for trachoma elimination in areas with hypoendemic disease.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.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.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 to C trachomatis antigens.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]; permutation P = .07).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.ClinicalTrials.gov Identifier: NCT02048007.
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- 2022
13. Macrolide and Nonmacrolide Resistance with Mass Azithromycin Distribution
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Catherine Cook, Elodie Lebas, Ramatou Maliki, Armin Hinterwirth, Kieran S O'Brien, Amza Abdou, Lina Zhong, Ahmed M. Arzika, Catherine E. Oldenburg, Thuy Doan, Marc Lipsitch, Lee Worden, Travis C. Porco, Cindi Chen, Eric D. Chow, Jeremy D. Keenan, and Thomas M. Lietman
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Male ,Veterinary medicine ,Clinical Trials and Supportive Activities ,Drug Resistance ,Azithromycin ,030204 cardiovascular system & hematology ,Medical and Health Sciences ,03 medical and health sciences ,0302 clinical medicine ,Clinical Research ,General & Internal Medicine ,parasitic diseases ,Humans ,Medicine ,Distribution (pharmacology) ,Niger ,030212 general & internal medicine ,Child ,Preschool ,Pediatric ,Mass distribution ,business.industry ,Bacterial ,Infant ,Evaluation of treatments and therapeutic interventions ,DNA ,General Medicine ,Anti-Bacterial Agents ,Gastrointestinal Microbiome ,Infectious Diseases ,Good Health and Well Being ,6.1 Pharmaceuticals ,Child Mortality ,Metagenome ,Mass Drug Administration ,HIV/AIDS ,Female ,Macrolides ,Antimicrobial Resistance ,Infection ,business ,Sequence Analysis ,medicine.drug - Abstract
BackgroundMass distribution of azithromycin to preschool children twice yearly for 2 years has been shown to reduce childhood mortality in sub-Saharan Africa but at the cost of amplifying macrolide resistance. The effects on the gut resistome, a reservoir of antimicrobial resistance genes in the body, of twice-yearly administration of azithromycin for a longer period are unclear.MethodsWe investigated the gut resistome of children after they received twice-yearly distributions of azithromycin for 4 years. In the Niger site of the MORDOR trial, we enrolled 30 villages in a concurrent trial in which they were randomly assigned to receive mass distribution of either azithromycin or placebo, offered to all children 1 to 59 months of age every 6 months for 4 years. Rectal swabs were collected at baseline, 36 months, and 48 months for analysis of the participants' gut resistome. The primary outcome was the ratio of macrolide-resistance determinants in the azithromycin group to those in the placebo group at 48 months.ResultsOver the entire 48-month period, the mean (±SD) coverage was 86.6±12% in the villages that received placebo and 83.2±16.4% in the villages that received azithromycin. A total of 3232 samples were collected during the entire trial period; of the samples obtained at the 48-month monitoring visit, 546 samples from 15 villages that received placebo and 504 from 14 villages that received azithromycin were analyzed. Determinants of macrolide resistance were higher in the azithromycin group than in the placebo group: 7.4 times as high (95% confidence interval [CI], 4.0 to 16.7) at 36 months and 7.5 times as high (95% CI, 3.8 to 23.1) at 48 months. Continued mass azithromycin distributions also selected for determinants of nonmacrolide resistance, including resistance to beta-lactam antibiotics, an antibiotic class prescribed frequently in this region of Africa.ConclusionsAmong villages assigned to receive mass distributions of azithromycin or placebo twice yearly for 4 years, antibiotic resistance was more common in the villages that received azithromycin than in those that received placebo. This trial showed that mass azithromycin distributions may propagate antibiotic resistance. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02047981.).
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- 2020
14. Post-antibiotic Ocular Surface Microbiome in Children: A Cluster-Randomized Trial
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Nisha R. Acharya, Thomas M. Lietman, Ahmed M. Arzika, Zhaoxia Zhou, Thuy Doan, Jeremy D. Keenan, Ramatou Maliki, Lee Worden, Cindi Chen, Travis C. Porco, Lina Zhong, and Armin Hinterwirth
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medicine.medical_specialty ,business.industry ,Extramural ,medicine.drug_class ,Microbiota ,Antibiotics ,MEDLINE ,Article ,Anti-Bacterial Agents ,Cornea ,Ophthalmology ,Internal medicine ,Humans ,Medicine ,Microbiome ,Cluster randomised controlled trial ,Child ,business ,Ocular surface ,Randomized Controlled Trials as Topic - Published
- 2020
15. Gut Resistome of Preschool Children After Prolonged Mass Azithromycin Distribution: A Cluster-randomized Trial
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Jeremy D. Keenan, Kevin Ruder, Kieran S O'Brien, Ahmed M. Arzika, Lee Worden, Travis C. Porco, Lina Zhong, Victoria Le, Cindi Chen, Catherine E. Oldenburg, Catherine Cook, Abdoul Naser Harouna, Alio Karamba Mankara, Thuy Doan, Elodie Lebas, Armin Hinterwirth, Ramatou Maliki, Benjamin F. Arnold, Zhaoxia Zhou, Thomas M. Lietman, and Amza Abdou
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0301 basic medicine ,Microbiology (medical) ,antibiotic resistance ,preschool children ,Clinical Trials and Supportive Activities ,Azithromycin ,Microbiology ,Medical and Health Sciences ,mass drug distribution ,03 medical and health sciences ,0302 clinical medicine ,Clinical Research ,Drug Resistance, Bacterial ,medicine ,Humans ,030212 general & internal medicine ,Niger ,Preschool child ,azithromycin ,Pediatric ,business.industry ,Biological Sciences ,Resistance monitoring ,Resistome ,Anti-Bacterial Agents ,gut resistome ,030104 developmental biology ,Infectious Diseases ,AcademicSubjects/MED00290 ,Macrolide resistance ,Child, Preschool ,Mass Drug Administration ,Brief Reports ,Macrolides ,Antimicrobial Resistance ,business ,Humanities ,medicine.drug - Abstract
Author(s): Arzika, Ahmed M; Maliki, Ramatou; Abdou, Amza; Mankara, Alio K; Harouna, Abdoul N; Cook, Catherine; Hinterwirth, Armin; Worden, Lee; Zhong, Lina; Chen, Cindi; Ruder, Kevin; Zhou, Zhaoxia; Lebas, Elodie; O'Brien, Kieran S; Oldenburg, Catherine E; Le, Victoria; Arnold, Benjamin F; Porco, Travis C; Keenan, Jeremy D; Lietman, Thomas M; Doan, Thuy | Abstract: We evaluated the gut resistome of children from communities treated with 10 twice-yearly azithromycin distributions. Although the macrolide resistance remained higher in the azithromycin arm, the selection of non-macrolide resistance observed at earlier time points did not persist. Longitudinal resistance monitoring should be a critical component of mass distribution programs.Clinical trials registrationNCT02047981.
- Published
- 2021
16. Simplified dosing of oral azithromycin for children 1–11 months old in child survival programmes: age-based and height-based dosing protocols
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Huiyu Hu, Ahmed Mamane Arzika, Ali Sie, Amza Abdou, Ramatou Maliki, Alio Karamba Mankara, Mamadou Outtara, Mamadou Bountogo, Valentin Boudo, Fanny Yago-Wienne, Issouf Bamba, Charles Knirsch, Paul Emerson, PJ Hooper, Elodie Lebas, Jessica Brogdon, Fanice Nyatigo, Catherine E Oldenburg, Thomas M Lietman, and Kieran S O'Brien
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Pediatric ,Trachoma ,Health Policy ,public health ,Clinical Trials and Supportive Activities ,Public Health, Environmental and Occupational Health ,Infant ,Azithromycin ,Body Height ,Anti-Bacterial Agents ,Good Health and Well Being ,Clinical Research ,Child Mortality ,child health ,Humans ,Child - Abstract
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.
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- 2022
17. Optimizing the Number of Child Deaths Averted with Mass Azithromycin Distribution
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Kieran S O'Brien, Jeremy D. Keenan, Catherine E. Oldenburg, Thomas M. Lietman, Ahmed M. Arzika, Ying Lin, and Ramatou Maliki
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Pediatrics ,medicine.medical_specialty ,medicine.drug_class ,030231 tropical medicine ,Antibiotics ,Azithromycin ,03 medical and health sciences ,0302 clinical medicine ,Virology ,medicine ,Risk of mortality ,Distribution (pharmacology) ,Humans ,Africa South of the Sahara ,Absolute number ,business.industry ,Infant ,Limiting ,Articles ,Anti-Bacterial Agents ,Infectious Diseases ,Child, Preschool ,Child Mortality ,Mass Drug Administration ,Parasitology ,Macrolides ,business ,medicine.drug - Abstract
Biannual mass azithromycin distribution to children younger than 5 years has been shown to reduce all-cause mortality in sub-Saharan Africa. Antibiotic-sparing approaches to azithromycin distribution, such as targeting to younger children who are at higher risk of mortality, are being considered by policymakers. We evaluated the absolute number of deaths averted in the Macrolides Oraux pour Réduire le Décès avec un Oeil sur la Résistance study in three age-groups: 1–5 months, 1–11 months, and 1–59 months. The number of deaths averted decreased from 729 (95% CI 492 to 966) in children aged 1–59 months to 297 (95% CI 168 to 427) and 126 (95% CI 43 to 209) in the 1- to 11-month and 1- to 5-month groups, respectively. Limiting antibiotic treatment to a subgroup of higher risk children may result in fewer deaths averted compared with treating all preschool children.
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- 2020
18. Gut microbiome alteration in MORDOR I: a community-randomized trial of mass azithromycin distribution
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Elodie Lebas, Susie Cummings, Eric D. Chow, Thomas M. Lietman, Travis C. Porco, Salissou Kane, Armin Hinterwirth, Irving Nachamkin, Catherine Cook, Lina Zhong, Ahmed M. Arzika, Jeremy D. Keenan, Amza Abdou, Lee Worden, S Sakar, Ramatou Maliki, Cindi Chen, and Thuy Doan
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Male ,0301 basic medicine ,medicine.drug_class ,Antibiotics ,Nigeria ,Drug resistance ,Azithromycin ,Gut flora ,General Biochemistry, Genetics and Molecular Biology ,Bacterial genetics ,Microbiology ,03 medical and health sciences ,0302 clinical medicine ,Antibiotic resistance ,Campylobacter Infections ,Drug Resistance, Bacterial ,medicine ,Humans ,Child ,biology ,Sequence Analysis, RNA ,Campylobacter ,Gene Expression Regulation, Bacterial ,General Medicine ,biology.organism_classification ,Gastrointestinal Microbiome ,Resistome ,030104 developmental biology ,Metagenomics ,Child, Preschool ,030220 oncology & carcinogenesis ,Child Mortality ,Macrolides ,medicine.drug - Abstract
The MORDOR I trial1, conducted in Niger, Malawi and Tanzania, demonstrated that mass azithromycin distribution to preschool children reduced childhood mortality1. However, the large but simple trial design precluded determination of the mechanisms involved. Here we examined the gut microbiome of preschool children from 30 Nigerien communities randomized to either biannual azithromycin or placebo. Gut microbiome γ-diversity was not significantly altered (P = 0.08), but the relative abundances of two Campylobacter species, along with another 33 gut bacteria, were significantly reduced in children treated with azithromycin at the 24-month follow-up. Metagenomic analysis revealed functional differences in gut bacteria between treatment groups. Resistome analysis showed an increase in macrolide resistance gene expression in gut microbiota in communities treated with azithromycin (P = 0.004). These results suggest that prolonged mass azithromycin distribution to reduce childhood mortality reduces certain gut bacteria, including known pathogens, while selecting for antibiotic resistance. Mass antibiotic administration to preschool children in Nigerien communities alters the relative abundances of 35 bacterial species in the gut microbiome, including enteric pathogens, but also increases expression of macrolide resistance genes.
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- 2019
19. Effect of biannual azithromycin distribution on antibody responses to malaria, bacterial, and protozoan pathogens in Niger
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Ahmed M, Arzika, Ramatou, Maliki, E Brook, Goodhew, Eric, Rogier, Jeffrey W, Priest, Elodie, Lebas, Kieran S, O'Brien, Victoria, Le, Catherine E, Oldenburg, Thuy, Doan, Travis C, Porco, Jeremy D, Keenan, Thomas M, Lietman, Diana L, Martin, and Benjamin F, Arnold
- Subjects
Giardiasis ,Rural Population ,Cryptosporidiosis ,Infant ,Azithromycin ,Anti-Bacterial Agents ,Malaria ,Child, Preschool ,Immunoglobulin G ,Campylobacter Infections ,Child Mortality ,Drug Resistance, Bacterial ,Salmonella Infections ,Humans ,Mass Drug Administration ,Niger ,Child ,Escherichia coli Infections ,Follow-Up Studies - Abstract
The MORDOR trial in Niger, Malawi, and Tanzania found that biannual mass distribution of azithromycin to children younger than 5 years led to a 13.5% reduction in all-cause mortality (NCT02048007). To help elucidate the mechanism for mortality reduction, we report IgG responses to 11 malaria, bacterial, and protozoan pathogens using a multiplex bead assay in pre-specified substudy of 30 communities in the rural Niger placebo-controlled trial over a three-year period (n = 5642 blood specimens, n = 3814 children ages 1-59 months). Mass azithromycin reduces Campylobacter spp. force of infection by 29% (hazard ratio = 0.71, 95% CI: 0.56, 0.89; P = 0.004) but serological measures show no significant differences between groups for other pathogens against a backdrop of high transmission. Results align with a recent microbiome study in the communities. Given significant sequelae of Campylobacter infection among preschool aged children, our results support an important mechanism through which biannual mass distribution of azithromycin likely reduces mortality in Niger.
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- 2021
20. Effect of biannual azithromycin distribution on antibody responses to malaria, bacterial, and protozoan pathogens among children: A cluster-randomized, placebo-controlled trial in Niger
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Ramatou Maliki, Elodie Lebas, Victoria Le, Jeffrey W. Priest, Diana L. Martin, Thomas M. Lietman, Eric Rogier, Kieran S. O’Brien, Travis C. Porco, Catherine E. Oldenburg, Thuy Doan, Ahmed M. Arzika, Jeremy D. Keenan, Benjamin F. Arnold, and E. Brook Goodhew
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medicine.medical_specialty ,business.industry ,Campylobacter ,Placebo-controlled study ,Azithromycin ,medicine.disease_cause ,medicine.disease ,Placebo ,Internal medicine ,medicine ,Population study ,Seroprevalence ,Seroconversion ,business ,Malaria ,medicine.drug - Abstract
BackgroundThe Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) trial in Niger, Malawi, and Tanzania found that biannual mass distribution of azithromycin to children younger than 5 years led to a 13.5% reduction in all-cause mortality. Additional endpoints in the trial have attempted to elucidate the mechanisms for mortality reduction. In this pre-specified secondary analysis, we assessed the effect of azithromycin compared with placebo on IgG- based measures of infectious disease exposure with a multiplex bead assay that included antigens to malaria parasites (Plasmodium falciparum, P. vivax, P. malariae, P. ovale), bacterial pathogens (Campylobacter spp., enterotoxigenic Escherichia coli, Vibrio cholerae, Salmonella enterica, Streptococcus pyogenes) and protozoans (Cryptosporidium parvum, Giardia duodenales).Methods and FindingsThirty communities in rural Niger were randomized 1:1 to biannual distributions of azithromycin or placebo among children ages 1-59 months. The analysis included 5,642 blood specimens collected from 3,814 children ages 1-59 months, measured at 6, 12, 24, and 36 months of follow-up in a repeated cross-sectional design. Campylobacter spp. seroprevalence averaged over all study visits was lower in azithromycin communities compared to placebo (91% vs 94%, difference = –3%, 95% CI: –5%, –1%; P=0.03), which corresponded to a 29% lower seroconversion rate (1.30 versus 1.84 seroconversions per year, hazard ratio = 0.71, 95% CI: 0.56, 0.89; P=0.004). Antibody-based measures of infection with P. falciparum and group A streptococcus were consistently lower in azithromycin communities, but were not statistically different from placebo, and there were no other differences across pathogens. Strengths of the study included masking of participants, investigators, and analysts, high treatment coverage, large sample size, and objective outcomes. Principal limitations included the timing of blood collection with respect to treatment (approximately 6 months later, which could have missed transient effects in the weeks immediately following treatment), and the durability of IgG response following clearance of infection. Both limitations would lead the trial to under-estimate effects on antibody-based measures of infection.ConclusionsThe reduction in Campylobacter spp. despite these limitations suggests an effect on carriage, findings which align with an independent metagenomic analysis of rectal swabs collected in the same villages and with previously reported reductions in dysentery-associated mortality. Given significant sequelae of Campylobacter infection among preschool aged children, our results support at least one possible mechanism through which biannual mass distribution of azithromycin likely reduced mortality in this study population.
- Published
- 2021
21. Azithromycin distribution and childhood mortality in compliance-related subgroups in Niger: complier average causal effect and spillovers in a cluster-randomized, placebo-controlled trial
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Jeremy D. Keenan, Catherine E. Oldenburg, Stefano M. Bertozzi, Farouk Manzo, Thomas M. Lietman, Benjamin F. Arnold, Ahmed M. Arzika, Ramatou Maliki, Abdou Amza, Elodie Lebas, Kieran S O'Brien, Travis C. Porco, Catherine Cook, and Alio Karamba Mankara
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medicine.medical_specialty ,Epidemiology ,Placebo-controlled study ,Azithromycin ,Rate ratio ,Placebo ,law.invention ,Randomized controlled trial ,law ,Internal medicine ,Infant Mortality ,medicine ,Humans ,Cluster randomised controlled trial ,Niger ,Child ,business.industry ,Mortality rate ,Infant ,General Medicine ,Confidence interval ,Anti-Bacterial Agents ,Child, Preschool ,Child Mortality ,Mass Drug Administration ,business ,medicine.drug - Abstract
Background Biannual azithromycin distribution to children 1–59 months old reduced all-cause mortality by 18% [incidence rate ratio (IRR) 0.82, 95% confidence interval (CI): 0.74, 0.90] in an intention-to-treat analysis of a randomized controlled trial in Niger. Estimation of the effect in compliance-related subgroups can support decision making around implementation of this intervention in programmatic settings. Methods The cluster-randomized, placebo-controlled design of the original trial enabled unbiased estimation of the effect of azithromycin on mortality rates in two subgroups: (i) treated children (complier average causal effect analysis); and (ii) untreated children (spillover effect analysis), using negative binomial regression. Results In Niger, 594 eligible communities were randomized to biannual azithromycin or placebo distribution and were followed from December 2014 to August 2017, with a mean treatment coverage of 90% [standard deviation (SD) 10%] in both arms. Subgroup analyses included 2581 deaths among treated children and 245 deaths among untreated children. Among treated children, the incidence rate ratio comparing mortality in azithromycin communities to placebo communities was 0.80 (95% CI: 0.72, 0.88), with mortality rates (deaths per 1000 person-years at risk) of 16.6 in azithromycin communities and 20.9 in placebo communities. Among untreated children, the incidence rate ratio was 0.91 (95% CI: 0.69, 1.21), with rates of 33.6 in azithromycin communities and 34.4 in placebo communities. Conclusions As expected, this analysis suggested similar efficacy among treated children compared with the intention-to-treat analysis. Though the results were consistent with a small spillover benefit to untreated children, this trial was underpowered to detect spillovers.
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- 2021
22. Additional file 1 of Age-based targeting of biannual azithromycin distribution for child survival in Niger: an adaptive cluster-randomized trial protocol (AVENIR)
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O’Brien, Kieran S., Arzika, Ahmed M., Amza, Abdou, Ramatou Maliki, Sani Ousmane, Boubacar Kadri, Beido Nassirou, Alio Karamba Mankara, Harouna, Abdoul Naser, Colby, Emily, Lebas, Elodie, Zijun Liu, Le, Victoria, Nguyen, William, Keenan, Jeremy D., Oldenburg, Catherine E., Porco, Travis C., Doan, Thuy, Arnold, Benjamin F., and Lietman, Thomas M.
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Data_FILES - Abstract
Additional file 1.
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- 2021
- Full Text
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23. Malaria Parasitemia and Nutritional Status during the Low Transmission Season in the Presence of Azithromycin Distribution among Preschool Children in Niger
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Ahmed M, Arzika, Ramatou, Maliki, Nameywa, Boubacar, Salissou, Kane, Catherine A, Cook, Elodie, Lebas, Ying, Lin, Kieran S, O'Brien, Ariana, Austin, Jeremy D, Keenan, Thomas M, Lietman, Catherine E, Oldenburg, and For The Mordor Study Group
- Subjects
Male ,medicine.medical_specialty ,030231 tropical medicine ,Nutritional Status ,Parasitemia ,Low transmission ,Azithromycin ,Placebo ,03 medical and health sciences ,0302 clinical medicine ,Virology ,Internal medicine ,parasitic diseases ,Medicine ,Distribution (pharmacology) ,Humans ,Niger ,business.industry ,Infant ,Nutritional status ,Articles ,medicine.disease ,Anti-Bacterial Agents ,Malaria ,Malnutrition ,Infectious Diseases ,Child, Preschool ,Mass Drug Administration ,Parasitology ,Female ,Seasons ,business ,medicine.drug - Abstract
The relationship between malaria and malnutrition is complicated, and existence of one may predispose or exacerbate the other. We evaluated the relationship between malaria parasitemia and nutritional status in children living in communities participating in a cluster-randomized trial of biannual azithromycin compared with placebo for prevention of childhood mortality. Data were collected during the low malaria transmission and low food insecurity season. Parasitemia was not associated with weight-for-height Z-score (24 months: P = 0.11 azithromycin communities, P = 0.75 placebo communities), weight-for-age Z-score (24 months: P = 0.83 azithromycin, P = 0.78 placebo), height-for-age Z-score (24 months: P = 0.30 azithromycin, P = 0.87 placebo), or mid-upper arm circumference (24 months: P = 0.12 azithromycin, P = 0.56 placebo). There was no statistically significant evidence of a difference in the relationship in communities receiving azithromycin or placebo. During the low transmission season, there was no evidence that malaria parasitemia and impaired nutritional status co-occur in children.
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- 2020
24. Macrolide Resistance in MORDOR I — A Cluster-Randomized Trial in Niger
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Travis C. Porco, Lina Zhong, Jeremy D. Keenan, Samarpita Sarkar, Thomas M. Lietman, Armin Hinterwirth, Thuy Doan, Cindi Chen, Ramatou Maliki, Susie Cummings, and Ahmed M. Arzika
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medicine.medical_specialty ,business.industry ,General Medicine ,Drug resistance ,030204 cardiovascular system & hematology ,bacterial infections and mycoses ,Antimicrobial ,Azithromycin ,03 medical and health sciences ,0302 clinical medicine ,Antibiotic resistance ,Macrolide resistance ,Internal medicine ,medicine ,030212 general & internal medicine ,Cluster randomised controlled trial ,business ,medicine.drug - Abstract
Macrolide Antimicrobial Resistance in MORDOR I In MORDOR I, azithromycin decreased mortality in children in Niger. In this report, it is shown that azithromycin also increased antimicrobial resista...
- Published
- 2019
25. Gut Microbial Diversity in Antibiotic-Naive Children After Systemic Antibiotic Exposure: A Randomized Controlled Trial
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Ramatou Maliki, Lina Zhong, Ahmed M. Arzika, Benjamin Vanderschelden, Travis C. Porco, J.S. Kim, Jeremy D. Keenan, Thuy Doan, Kathryn J. Ray, Sun Y. Cotter, Zhaoxia Zhou, and Thomas M. Lietman
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0301 basic medicine ,Male ,Antibiotics ,Administration, Oral ,gut microbiome ,Azithromycin ,Medical and Health Sciences ,antibiotics ,law.invention ,Placebos ,Randomized controlled trial ,law ,Oral administration ,RNA, Ribosomal, 16S ,Cluster Analysis ,Niger ,Child ,Phylogeny ,Pediatric ,education.field_of_study ,Biodiversity ,Biological Sciences ,Anti-Bacterial Agents ,Infectious Diseases ,5.1 Pharmaceuticals ,Child, Preschool ,6.1 Pharmaceuticals ,Administration ,Female ,Development of treatments and therapeutic interventions ,Sequence Analysis ,medicine.drug ,Microbiology (medical) ,Oral ,medicine.medical_specialty ,16S ,medicine.drug_class ,Population ,Clinical Trials and Supportive Activities ,Placebo ,DNA, Ribosomal ,Microbiology ,03 medical and health sciences ,children ,Clinical Research ,Internal medicine ,Complementary and Integrative Health ,medicine ,Major Article ,Humans ,education ,Preschool ,Feces ,Nutrition ,Ribosomal ,Bacteria ,business.industry ,Infant ,Evaluation of treatments and therapeutic interventions ,Sequence Analysis, DNA ,DNA ,Confidence interval ,Gastrointestinal Microbiome ,Gastrointestinal Tract ,030104 developmental biology ,randomized controlled trial ,RNA ,business ,human activities - Abstract
Background Antibiotic exposure can alter the gut microbiome. We evaluate the effects of azithromycin on the gut microbiome diversity of children from an antibiotic-naive community in Niger. Methods A population-based sample of 80 children aged 1-60 months in the Dosso region of Niger was randomized to receive a single dose of either oral azithromycin or placebo. Fecal samples were collected immediately before treatment and 5 days after treatment for 16S rRNA gene sequencing. The prespecified outcome was α-diversity (inverse Simpson's α-diversity index), with secondary outcomes of β and γ Simpson's and Shannon's diversities. Results At 5 days after treatment, 40 children aged 1-60 months were analyzed in the azithromycin-treated group and 40 children in the placebo-treated group. Diversity of the gut microbiome was significantly lower in the treated group (inverse Simpson's α-diversity, 5.03; 95% confidence interval [CI], 4.08-6.14) than in the placebo group (6.91; 95% CI, 5.82-8.21; P = .03). Similarly, the Shannon's α-diversity was lower in the treated group (10.60; 95% CI, 8.82-12.36) than the placebo group (15.42; 95% CI, 13.24-17.80; P = .004). Simpson's community-level (γ) diversity decreased with azithromycin exposure from 17.72 (95% CI, 13.80-20.21) to 10.10 (95% CI, 7.80-11.40; P = .00008), although β-diversity was not significantly reduced (2.56, 95% CI, 1.88-3.12; to 2.01, 95% CI, 1.46-2.51; P = .26). Conclusions Oral administration of azithromycin definitively decreases the diversity of the gut microbiome of children in an antibiotic-naive community. Clinical Trials Registration NCT02048007.
- Published
- 2017
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