Authors:
, , , , , , , , , , , , , , , , , and
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
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-
1.
UNICEF , 2019. The State of the World’s Children 2019. Children, Food, and Nutrition: Growing Well in a Changing World. New York, NY: UNICEF.
-
2.
Black RE et al.2013. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet 382: 427–451.
-
3.
Alcoba G, Kerac M, Breysse S, Salpeteur C, Galetto-Lacour A, Briend A, Gervaix A , 2013. Do children with uncomplicated severe acute malnutrition need antibiotics? A systematic review and meta-analysis. PLOS ONE 8: e53184.
-
4.
Bourke CD, Berkley JA, Prendergast AJ , 2016. Immune dysfunction as a cause and consequence of malnutrition. Trends Immunol 37: 386–398.
-
5.
Page AL et al.2013. Infections in children admitted with complicated severe acute malnutrition in Niger. PLOS ONE 8: e68699.
-
6.
Jones KD, Berkley JA , 2014. Severe acute malnutrition and infection. Paediatr Int Child Health 34 (Suppl 1): S1–S29.
-
7.
World Health Organization , 2013. Guideline: Updates on the Management of Severe Acute Malnutrition in Infants and Children. Geneva, Switzerland: WHO.
-
8.
Trehan I, Goldbach HS, LaGrone LN, Meuli GJ, Wang RJ, Maleta KM, Manary MJ , 2013. Antibiotics as part of the management of severe acute malnutrition. N Engl J Med 368: 425–435.
-
9.
Isanaka S et al.2016. Routine amoxicillin for uncomplicated severe acute malnutrition in children. N Engl J Med 374: 444–453.
-
10.
Trehan I, Schechtman KB, Manary MJ , 2016. Amoxicillin for severe acute malnutrition in children. N Engl J Med 375: 191.
-
11.
Million M, Lagier JC, Raoult D , 2017. Meta-analysis on efficacy of amoxicillin in uncomplicated severe acute malnutrition. Microb Pathog 106: 76–77.
-
12.
Das JK, Salam RA, Saeed M, Kazmi FA, Bhutta ZA , 2020. Effectiveness of interventions for managing acute malnutrition in children under five years of age in low-income and middle-income countries: a systematic review and meta-analysis. Nutrients 12: 116.
-
13.
Keenan JD et al.2018. Azithromycin to reduce childhood mortality in sub-Saharan Africa. N Engl J Med 378: 1583–1592.
-
14.
O’Brien KS et al.2020. Biannual azithromycin distribution and child mortality among malnourished children: a subgroup analysis of the MORDOR cluster-randomized trial in Niger. PLoS Med 17: e1003285.
-
15.
Langtry HD, Balfour JA , 1998. Azithromycin—a review of its use in paediatric. Drugs 56: 273–297.
-
16.
Coles CL, Levens J, Seidman JC, Mkocha H, Munoz B, West S , 2012. Mass distribution of azithromycin for trachoma control is associated with short-term reduction in risk of acute lower respiratory infection in young children. Pediatr Infect Dis J 31: 341–346.
-
17.
Coles CL, Seidman JC, Levens J, Mkocha H, Munoz B, West S , 2011. Association of mass treatment with azithromycin in trachoma-endemic communities with short-term reduced risk of diarrhea in young children. Am J Trop Med Hyg 85: 691–696.
-
18.
Phiri MD et al., 2021. The duration of protection from azithromycin against malaria, acute respiratory, gastro-intestinal and skin infections when given alongside seasonal malaria chemoprevention: secondary analyses of data from a clinical trial in Houndé, Burkina Faso and Bougouni, Mali. Clin Infect Dis 73: e2379–e2386.
-
19.
Blumer JL , 2005. Evolution of a new drug formulation: the rationale for high-dose, short-course therapy with azithromycin. Int J Antimicrob Agents 26 (Suppl 3): S143–S147.
-
20.
Rogawski ET et al.2017. Use of antibiotics in children younger than two years in eight countries: a prospective cohort study. Bull World Health Organ 95: 49–61.
-
21.
Sie A et al.2018. Effect of antibiotics on short-term growth among children in Burkina Faso: a randomized trial. Am J Trop Med Hyg 99: 789–796.
-
22.
Bell BG, Schellevis F, Stobberingh E, Goossens H, Pringle M , 2014. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance. BMC Infect Dis 14: 13.
-
23.
2014. Protocole Nationale: Prise en charge integrée de la malnutrition aiguë (PCIMA). Ouagadougou, Burkina Faso: Ministere de la Santé Burkina Faso.
-
24.
O’Brien KS, Sié A, Dah C, Ourohire M, Arzika AM, Boudo V, Lebas E, Godwin WW, Arnold BF, Oldenburg CE , 2021. Azithromycin for uncomplicated severe acute malnutrition: study protocol for a pilot randomized controlled trial. Pilot Feasibility Stud 7: 97.
-
25.
Sie A et al.2022. Azithromycin versus amoxicillin and malarial parasitemia among children with uncomplicated severe acute malnutrition: a randomized controlled trial. Am J Trop Med Hyg 106: 351–355.
-
26.
WHO Multicentre Growth Reference Study Group , 2006. WHO Child Growth Standards: Length/Height-for-Age, Weight-for-Age, Weight-for-Length, Weight-for-Height and Body Mass Index for-Age: Methods and Development. Geneva, Switzerland: World Health Organization, 312.
-
27.
Zou G , 2004. A modified poisson regression approach to prospective studies with binary data. Am J Epidemiol 159: 702–706.
-
28.
Stobaugh HC, Mayberry A, McGrath M, Bahwere P, Zagre NM, Manary MJ, Black R, Lelijveld N , 2019. Relapse after severe acute malnutrition: a systematic literature review and secondary data analysis. Matern Child Nutr 15: e12702.
-
29.
2011. The Sphere Handbook: Humanitarian Charter and Minimum Standards in Humanitarian Response. Geneva, Switzerland: The Sphere Project.
-
30.
Desyibelew HD, Bayih MT, Baraki AG, Dadi AF , 2020. The recovery rate from severe acute malnutrition among under-five years of children remains low in sub-Saharan Africa. A systematic review and meta-analysis of observational studies. PLOS ONE 15: e0229698.
-
31.
Belesova K, Gasparrini A, Sié A, Sauerborn R, Wilkinson P , 2017. Household cereal crop harvest and children’s nutritional status in rural Burkina Faso. Environ Health 16: 65.
-
32.
Belesova K, Gasparrini A, Sié A, Sauerborn R, Wilkinson P , 2017. Annual crop-yield variation, child survival, and nutrition among subsistence farmers in Burkina Faso. Am J Epidemiol 187: 242–250.
-
33.
Taylor HR, Burton MJ, Haddad D, West S, Wright H , 2014. Trachoma. Lancet 384: 2142–2152.
-
34.
Oldenburg CE et al.2018. Safety of azithromycin in infants under six months of age in Niger: a community randomized trial. PLoS Negl Trop Dis 12: e0006950.
-
35.
Doan T et al.2019. Gut microbiome alteration in MORDOR I: a community-randomized trial of mass azithromycin distribution. Nat Med 25: 1370–1376.
-
36.
Jimenez SG, Heine RG, Ward PB, Robins-Browne RM , 1999. Campylobacter upsaliensis gastroenteritis in childhood. Pediatr Infect Dis J 18: 988–992.
-
37.
Bourke B, Chan VL, Sherman P , 1998. Campylobacter upsaliensis: waiting in the wings. Clin Microbiol Rev 11: 440–449.
-
38.
Sire JM, Garin B, Chartier L, Fall NK, Tall A, Seck A, Weill FX, Breurec S, Vray M , 2013. Community-acquired infectious diarrhoea in children under 5 years of age in Dakar, Senegal. Paediatr Int Child Health 33: 139–144.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 12487 | 2754 | 428 |
| Full Text Views | 195 | 19 | 2 |
| PDF Downloads | 162 | 21 | 2 |
Comparing Azithromycin to Amoxicillin in the Management of Uncomplicated Severe Acute Malnutrition in Burkina Faso: A Pilot Randomized Trial
Kieran S. O’Brien
Kieran S. O’Brien
Francis I Proctor Foundation, University of California, San Francisco, California;
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Ali Sié
Ali Sié
Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso;
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Clarisse Dah
Clarisse Dah
Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso;
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Millogo Ourohiré
Millogo Ourohiré
Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso;
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Moussa Ouedraogo
Moussa Ouedraogo
Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso;
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Valentin Boudo
Valentin Boudo
Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso;
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Ahmed Arzika
Ahmed Arzika
Centre de Recherche et Interventions en Santé Publique, Niamey, Niger;
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Elodie Lebas
Elodie Lebas
Francis I Proctor Foundation, University of California, San Francisco, California;
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Fanice Nyatigo
Fanice Nyatigo
Francis I Proctor Foundation, University of California, San Francisco, California;
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William Godwin
William Godwin
Francis I Proctor Foundation, University of California, San Francisco, California;
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J. Daniel Kelly
J. Daniel Kelly
Francis I Proctor Foundation, University of California, San Francisco, California;
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Benjamin F. Arnold
Benjamin F. Arnold
Francis I Proctor Foundation, University of California, San Francisco, California;
Department of Ophthalmology, University of California, San Francisco, California;
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Department of Ophthalmology, University of California, San Francisco, California;
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Catherine E. Oldenburg
Catherine E. Oldenburg
Francis I Proctor Foundation, University of California, San Francisco, California;
Department of Ophthalmology, University of California, San Francisco, California;
Department of Epidemiology & Biostatistics, University of California, San Francisco, California
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Department of Ophthalmology, University of California, San Francisco, California;
Department of Epidemiology & Biostatistics, University of California, San Francisco, California
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ABSTRACT.
Azithromycin is a promising alternative to amoxicillin in the management of uncomplicated severe acute malnutrition (SAM) as it can be administered as a single dose and has efficacy against several pathogens causing infectious disease and mortality in children under 5. In this pilot trial, we aimed to establish the feasibility of a larger randomized controlled trial and provide preliminary evidence comparing the effect of azithromycin to amoxicillin on weight gain in children with uncomplicated SAM. We enrolled children 6–59 months old with uncomplicated SAM at six healthcare centers in Burkina Faso. Participants were randomized to a single dose of azithromycin or a 7-day course of amoxicillin and followed weekly until nutritional recovery and again at 8 weeks. Apart from antibiotics, participants received standard of care, which includes ready-to-use therapeutic food. Primary feasibility outcomes included enrollment potential, refusals, and loss to follow-up. The primary clinical outcome was weight gain (g/kg/day) over 8 weeks. Outcome assessors were masked. Between June and October 2020, 312 children were screened, 301 were enrolled with zero refusals, and 282 (93.6%) completed the 8-week visit. Average weight gain was 2.5 g/kg/day (standard deviation [SD] 2.0) in the azithromycin group and 2.6 (SD 1.7) in the amoxicillin group (mean difference −0.1, 95% CI −0.5 to 0.3, P = 0.63). Fewer adverse events were reported in the azithromycin group (risk ratio 0.50, 95% CI 0.31–0.82, P = 0.006). With strong enrollment and follow-up, a fully powered trial in this setting is feasible.
Author Notes
Financial support: This work was supported by the National Institutes of Health—National Institute of Child Health and Development (R21HD100932) and a UCSF REAC award. The funders reviewed the study design and had no role in the conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or in the decision to submit the manuscript for publication.
Authors’ addresses: Kieran S. O’Brien, Elodie Lebas, Fanice Nyatigo, William Godwin, and J. Daniel Kelly, Francis I Proctor Foundation, University of California, San Francisco, CA, E-mails: kieran.obrien@ucsf.edu, elodie.lebas@ucsf.edu, fanice.nyatigo@ucsf.edu, wgodwinner@gmail.com, and dan.kelly@ucsf.edu. Ali Sié, Clarisse Dah, Ourohiré Millogo, Moussa Ouedraogo, and Valentin Boudo, Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso, E-mails: sieali@yahoo.fr, n.clarissedah@yahoo.fr, ourohire2001@yahoo.fr, moussaoued0202@gmail.com, and valentinboudo@gmail.com. Ahmed Arzika, Centre de Recherche et Interventions en Santé Publique, Niamey, Niger, E-mail: ahmedarzika@gmail.com. Benjamin F. Arnold, Francis I Proctor Foundation, University of California, San Francisco, CA, and Department of Ophthalmology, University of California, San Francisco, CA, E-mail: ben.arnold@ucsf.edu. Catherine E. Oldenburg, Francis I Proctor Foundation, University of California, San Francisco, CA, Department of Ophthalmology, University of California, San Francisco, CA, and Department of Epidemiology & Biostatistics, University of California, San Francisco, CA, E-mail: catherine.oldenburg@ucsf.edu.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
UNICEF , 2019. The State of the World’s Children 2019. Children, Food, and Nutrition: Growing Well in a Changing World. New York, NY: UNICEF.
-
2.
Black RE et al.2013. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet 382: 427–451.
-
3.
Alcoba G, Kerac M, Breysse S, Salpeteur C, Galetto-Lacour A, Briend A, Gervaix A , 2013. Do children with uncomplicated severe acute malnutrition need antibiotics? A systematic review and meta-analysis. PLOS ONE 8: e53184.
-
4.
Bourke CD, Berkley JA, Prendergast AJ , 2016. Immune dysfunction as a cause and consequence of malnutrition. Trends Immunol 37: 386–398.
-
5.
Page AL et al.2013. Infections in children admitted with complicated severe acute malnutrition in Niger. PLOS ONE 8: e68699.
-
6.
Jones KD, Berkley JA , 2014. Severe acute malnutrition and infection. Paediatr Int Child Health 34 (Suppl 1): S1–S29.
-
7.
World Health Organization , 2013. Guideline: Updates on the Management of Severe Acute Malnutrition in Infants and Children. Geneva, Switzerland: WHO.
-
8.
Trehan I, Goldbach HS, LaGrone LN, Meuli GJ, Wang RJ, Maleta KM, Manary MJ , 2013. Antibiotics as part of the management of severe acute malnutrition. N Engl J Med 368: 425–435.
-
9.
Isanaka S et al.2016. Routine amoxicillin for uncomplicated severe acute malnutrition in children. N Engl J Med 374: 444–453.
-
10.
Trehan I, Schechtman KB, Manary MJ , 2016. Amoxicillin for severe acute malnutrition in children. N Engl J Med 375: 191.
-
11.
Million M, Lagier JC, Raoult D , 2017. Meta-analysis on efficacy of amoxicillin in uncomplicated severe acute malnutrition. Microb Pathog 106: 76–77.
-
12.
Das JK, Salam RA, Saeed M, Kazmi FA, Bhutta ZA , 2020. Effectiveness of interventions for managing acute malnutrition in children under five years of age in low-income and middle-income countries: a systematic review and meta-analysis. Nutrients 12: 116.
-
13.
Keenan JD et al.2018. Azithromycin to reduce childhood mortality in sub-Saharan Africa. N Engl J Med 378: 1583–1592.
-
14.
O’Brien KS et al.2020. Biannual azithromycin distribution and child mortality among malnourished children: a subgroup analysis of the MORDOR cluster-randomized trial in Niger. PLoS Med 17: e1003285.
-
15.
Langtry HD, Balfour JA , 1998. Azithromycin—a review of its use in paediatric. Drugs 56: 273–297.
-
16.
Coles CL, Levens J, Seidman JC, Mkocha H, Munoz B, West S , 2012. Mass distribution of azithromycin for trachoma control is associated with short-term reduction in risk of acute lower respiratory infection in young children. Pediatr Infect Dis J 31: 341–346.
-
17.
Coles CL, Seidman JC, Levens J, Mkocha H, Munoz B, West S , 2011. Association of mass treatment with azithromycin in trachoma-endemic communities with short-term reduced risk of diarrhea in young children. Am J Trop Med Hyg 85: 691–696.
-
18.
Phiri MD et al., 2021. The duration of protection from azithromycin against malaria, acute respiratory, gastro-intestinal and skin infections when given alongside seasonal malaria chemoprevention: secondary analyses of data from a clinical trial in Houndé, Burkina Faso and Bougouni, Mali. Clin Infect Dis 73: e2379–e2386.
-
19.
Blumer JL , 2005. Evolution of a new drug formulation: the rationale for high-dose, short-course therapy with azithromycin. Int J Antimicrob Agents 26 (Suppl 3): S143–S147.
-
20.
Rogawski ET et al.2017. Use of antibiotics in children younger than two years in eight countries: a prospective cohort study. Bull World Health Organ 95: 49–61.
-
21.
Sie A et al.2018. Effect of antibiotics on short-term growth among children in Burkina Faso: a randomized trial. Am J Trop Med Hyg 99: 789–796.
-
22.
Bell BG, Schellevis F, Stobberingh E, Goossens H, Pringle M , 2014. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance. BMC Infect Dis 14: 13.
-
23.
2014. Protocole Nationale: Prise en charge integrée de la malnutrition aiguë (PCIMA). Ouagadougou, Burkina Faso: Ministere de la Santé Burkina Faso.
-
24.
O’Brien KS, Sié A, Dah C, Ourohire M, Arzika AM, Boudo V, Lebas E, Godwin WW, Arnold BF, Oldenburg CE , 2021. Azithromycin for uncomplicated severe acute malnutrition: study protocol for a pilot randomized controlled trial. Pilot Feasibility Stud 7: 97.
-
25.
Sie A et al.2022. Azithromycin versus amoxicillin and malarial parasitemia among children with uncomplicated severe acute malnutrition: a randomized controlled trial. Am J Trop Med Hyg 106: 351–355.
-
26.
WHO Multicentre Growth Reference Study Group , 2006. WHO Child Growth Standards: Length/Height-for-Age, Weight-for-Age, Weight-for-Length, Weight-for-Height and Body Mass Index for-Age: Methods and Development. Geneva, Switzerland: World Health Organization, 312.
-
27.
Zou G , 2004. A modified poisson regression approach to prospective studies with binary data. Am J Epidemiol 159: 702–706.
-
28.
Stobaugh HC, Mayberry A, McGrath M, Bahwere P, Zagre NM, Manary MJ, Black R, Lelijveld N , 2019. Relapse after severe acute malnutrition: a systematic literature review and secondary data analysis. Matern Child Nutr 15: e12702.
-
29.
2011. The Sphere Handbook: Humanitarian Charter and Minimum Standards in Humanitarian Response. Geneva, Switzerland: The Sphere Project.
-
30.
Desyibelew HD, Bayih MT, Baraki AG, Dadi AF , 2020. The recovery rate from severe acute malnutrition among under-five years of children remains low in sub-Saharan Africa. A systematic review and meta-analysis of observational studies. PLOS ONE 15: e0229698.
-
31.
Belesova K, Gasparrini A, Sié A, Sauerborn R, Wilkinson P , 2017. Household cereal crop harvest and children’s nutritional status in rural Burkina Faso. Environ Health 16: 65.
-
32.
Belesova K, Gasparrini A, Sié A, Sauerborn R, Wilkinson P , 2017. Annual crop-yield variation, child survival, and nutrition among subsistence farmers in Burkina Faso. Am J Epidemiol 187: 242–250.
-
33.
Taylor HR, Burton MJ, Haddad D, West S, Wright H , 2014. Trachoma. Lancet 384: 2142–2152.
-
34.
Oldenburg CE et al.2018. Safety of azithromycin in infants under six months of age in Niger: a community randomized trial. PLoS Negl Trop Dis 12: e0006950.
-
35.
Doan T et al.2019. Gut microbiome alteration in MORDOR I: a community-randomized trial of mass azithromycin distribution. Nat Med 25: 1370–1376.
-
36.
Jimenez SG, Heine RG, Ward PB, Robins-Browne RM , 1999. Campylobacter upsaliensis gastroenteritis in childhood. Pediatr Infect Dis J 18: 988–992.
-
37.
Bourke B, Chan VL, Sherman P , 1998. Campylobacter upsaliensis: waiting in the wings. Clin Microbiol Rev 11: 440–449.
-
38.
Sire JM, Garin B, Chartier L, Fall NK, Tall A, Seck A, Weill FX, Breurec S, Vray M , 2013. Community-acquired infectious diarrhoea in children under 5 years of age in Dakar, Senegal. Paediatr Int Child Health 33: 139–144.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 12487 | 2754 | 428 |
| Full Text Views | 195 | 19 | 2 |
| PDF Downloads | 162 | 21 | 2 |