Effect of scheduled antimicrobial and nicotinamide treatment on linear growth in children in rural Tanzania: A factorial randomized, double-blind, placebo-controlled trial.

<h4>Background</h4>Stunting among children in low-resource settings is associated with enteric pathogen carriage and micronutrient deficiencies. Our goal was to test whether administration of scheduled antimicrobials and daily nicotinamide improved linear growth in a region with a high p...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Mark D DeBoer, James A Platts-Mills, Sarah E Elwood, Rebecca J Scharf, Joann M McDermid, Anne W Wanjuhi, Samwel Jatosh, Siphael Katengu, Tarina C Parpia, Elizabeth T Rogawski McQuade, Jean Gratz, Erling Svensen, Jonathan R Swann, Jeffrey R Donowitz, Paschal Mdoe, Sokoine Kivuyo, Eric R Houpt, Estomih Mduma
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/2adec5a5ca7141e4a2d641862c020630
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2adec5a5ca7141e4a2d641862c020630
record_format	dspace
spelling	oai:doaj.org-article:2adec5a5ca7141e4a2d641862c0206302021-12-02T19:55:45ZEffect of scheduled antimicrobial and nicotinamide treatment on linear growth in children in rural Tanzania: A factorial randomized, double-blind, placebo-controlled trial.1549-12771549-167610.1371/journal.pmed.1003617https://doaj.org/article/2adec5a5ca7141e4a2d641862c0206302021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pmed.1003617https://doaj.org/toc/1549-1277https://doaj.org/toc/1549-1676<h4>Background</h4>Stunting among children in low-resource settings is associated with enteric pathogen carriage and micronutrient deficiencies. Our goal was to test whether administration of scheduled antimicrobials and daily nicotinamide improved linear growth in a region with a high prevalence of stunting and enteric pathogen carriage.<h4>Methods and findings</h4>We performed a randomized, 2 × 2 factorial, double-blind, placebo-controlled trial in the area around Haydom, Tanzania. Mother-child dyads were enrolled by age 14 days and followed with monthly home visits and every 3-month anthropometry assessments through 18 months. Those randomized to the antimicrobial arm received 2 medications (versus corresponding placebos): azithromycin (single dose of 20 mg/kg) at months 6, 9, 12, and 15 and nitazoxanide (3-day course of 100 mg twice daily) at months 12 and 15. Those randomized to nicotinamide arm received daily nicotinamide to the mother (250 mg pills months 0 to 6) and to the child (100 mg sachets months 6 to 18). Primary outcome was length-for-age z-score (LAZ) at 18 months in the modified intention-to-treat group. Between September 5, 2017 and August 31, 2018, 1,188 children were randomized, of whom 1,084 (n = 277 placebo/placebo, 273 antimicrobial/placebo, 274 placebo/nicotinamide, and 260 antimicrobial/nicotinamide) were included in the modified intention-to-treat analysis. The study was suspended for a 3-month period by the Tanzanian National Institute for Medical Research (NIMR) because of concerns related to the timing of laboratory testing and the total number of serious adverse events (SAEs); this resulted in some participants receiving their final study assessment late. There was a high prevalence of stunting overall (533/1,084, 49.2%). Mean 18-month LAZ did not differ between groups for either intervention (mean LAZ with 95% confidence interval [CI]: antimicrobial: -2.05 CI -2.13, -1.96, placebo: -2.05 CI -2.14, -1.97; mean difference: 0.01 CI -0.13, 0.11, p = 0.91; nicotinamide: -2.06 CI -2.13, -1.95, placebo: -2.04 CI -2.14, -1.98, mean difference 0.03 CI -0.15, 0.09, p = 0.66). There was no difference in LAZ for either intervention after adjusting for possible confounders (baseline LAZ, age in days at 18-month measurement, ward, hospital birth, birth month, years of maternal education, socioeconomic status (SES) quartile category, sex, whether the mother was a member of the Datoga tribe, and mother's height). Adverse events (AEs) and SAEs were overall similar between treatment groups for both the nicotinamide and antimicrobial interventions. Key limitations include the absence of laboratory measures of pathogen carriage and nicotinamide metabolism to provide context for the negative findings.<h4>Conclusions</h4>In this study, we observed that neither scheduled administration of azithromycin and nitazoxanide nor daily provision of nicotinamide was associated with improved growth in this resource-poor setting with a high force of enteric infections. Further research remains critical to identify interventions toward improved early childhood growth in challenging conditions.<h4>Trial registration</h4>ClinicalTrials.gov NCT03268902.Mark D DeBoerJames A Platts-MillsSarah E ElwoodRebecca J ScharfJoann M McDermidAnne W WanjuhiSamwel JatoshSiphael KatenguTarina C ParpiaElizabeth T Rogawski McQuadeJean GratzErling SvensenJonathan R SwannJeffrey R DonowitzPaschal MdoeSokoine KivuyoEric R HouptEstomih MdumaPublic Library of Science (PLoS)articleMedicineRENPLoS Medicine, Vol 18, Iss 9, p e1003617 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Mark D DeBoer James A Platts-Mills Sarah E Elwood Rebecca J Scharf Joann M McDermid Anne W Wanjuhi Samwel Jatosh Siphael Katengu Tarina C Parpia Elizabeth T Rogawski McQuade Jean Gratz Erling Svensen Jonathan R Swann Jeffrey R Donowitz Paschal Mdoe Sokoine Kivuyo Eric R Houpt Estomih Mduma Effect of scheduled antimicrobial and nicotinamide treatment on linear growth in children in rural Tanzania: A factorial randomized, double-blind, placebo-controlled trial.
description	<h4>Background</h4>Stunting among children in low-resource settings is associated with enteric pathogen carriage and micronutrient deficiencies. Our goal was to test whether administration of scheduled antimicrobials and daily nicotinamide improved linear growth in a region with a high prevalence of stunting and enteric pathogen carriage.<h4>Methods and findings</h4>We performed a randomized, 2 × 2 factorial, double-blind, placebo-controlled trial in the area around Haydom, Tanzania. Mother-child dyads were enrolled by age 14 days and followed with monthly home visits and every 3-month anthropometry assessments through 18 months. Those randomized to the antimicrobial arm received 2 medications (versus corresponding placebos): azithromycin (single dose of 20 mg/kg) at months 6, 9, 12, and 15 and nitazoxanide (3-day course of 100 mg twice daily) at months 12 and 15. Those randomized to nicotinamide arm received daily nicotinamide to the mother (250 mg pills months 0 to 6) and to the child (100 mg sachets months 6 to 18). Primary outcome was length-for-age z-score (LAZ) at 18 months in the modified intention-to-treat group. Between September 5, 2017 and August 31, 2018, 1,188 children were randomized, of whom 1,084 (n = 277 placebo/placebo, 273 antimicrobial/placebo, 274 placebo/nicotinamide, and 260 antimicrobial/nicotinamide) were included in the modified intention-to-treat analysis. The study was suspended for a 3-month period by the Tanzanian National Institute for Medical Research (NIMR) because of concerns related to the timing of laboratory testing and the total number of serious adverse events (SAEs); this resulted in some participants receiving their final study assessment late. There was a high prevalence of stunting overall (533/1,084, 49.2%). Mean 18-month LAZ did not differ between groups for either intervention (mean LAZ with 95% confidence interval [CI]: antimicrobial: -2.05 CI -2.13, -1.96, placebo: -2.05 CI -2.14, -1.97; mean difference: 0.01 CI -0.13, 0.11, p = 0.91; nicotinamide: -2.06 CI -2.13, -1.95, placebo: -2.04 CI -2.14, -1.98, mean difference 0.03 CI -0.15, 0.09, p = 0.66). There was no difference in LAZ for either intervention after adjusting for possible confounders (baseline LAZ, age in days at 18-month measurement, ward, hospital birth, birth month, years of maternal education, socioeconomic status (SES) quartile category, sex, whether the mother was a member of the Datoga tribe, and mother's height). Adverse events (AEs) and SAEs were overall similar between treatment groups for both the nicotinamide and antimicrobial interventions. Key limitations include the absence of laboratory measures of pathogen carriage and nicotinamide metabolism to provide context for the negative findings.<h4>Conclusions</h4>In this study, we observed that neither scheduled administration of azithromycin and nitazoxanide nor daily provision of nicotinamide was associated with improved growth in this resource-poor setting with a high force of enteric infections. Further research remains critical to identify interventions toward improved early childhood growth in challenging conditions.<h4>Trial registration</h4>ClinicalTrials.gov NCT03268902.
format	article
author	Mark D DeBoer James A Platts-Mills Sarah E Elwood Rebecca J Scharf Joann M McDermid Anne W Wanjuhi Samwel Jatosh Siphael Katengu Tarina C Parpia Elizabeth T Rogawski McQuade Jean Gratz Erling Svensen Jonathan R Swann Jeffrey R Donowitz Paschal Mdoe Sokoine Kivuyo Eric R Houpt Estomih Mduma
author_facet	Mark D DeBoer James A Platts-Mills Sarah E Elwood Rebecca J Scharf Joann M McDermid Anne W Wanjuhi Samwel Jatosh Siphael Katengu Tarina C Parpia Elizabeth T Rogawski McQuade Jean Gratz Erling Svensen Jonathan R Swann Jeffrey R Donowitz Paschal Mdoe Sokoine Kivuyo Eric R Houpt Estomih Mduma
author_sort	Mark D DeBoer
title	Effect of scheduled antimicrobial and nicotinamide treatment on linear growth in children in rural Tanzania: A factorial randomized, double-blind, placebo-controlled trial.
title_short	Effect of scheduled antimicrobial and nicotinamide treatment on linear growth in children in rural Tanzania: A factorial randomized, double-blind, placebo-controlled trial.
title_full	Effect of scheduled antimicrobial and nicotinamide treatment on linear growth in children in rural Tanzania: A factorial randomized, double-blind, placebo-controlled trial.
title_fullStr	Effect of scheduled antimicrobial and nicotinamide treatment on linear growth in children in rural Tanzania: A factorial randomized, double-blind, placebo-controlled trial.
title_full_unstemmed	Effect of scheduled antimicrobial and nicotinamide treatment on linear growth in children in rural Tanzania: A factorial randomized, double-blind, placebo-controlled trial.
title_sort	effect of scheduled antimicrobial and nicotinamide treatment on linear growth in children in rural tanzania: a factorial randomized, double-blind, placebo-controlled trial.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/2adec5a5ca7141e4a2d641862c020630
work_keys_str_mv	AT markddeboer effectofscheduledantimicrobialandnicotinamidetreatmentonlineargrowthinchildreninruraltanzaniaafactorialrandomizeddoubleblindplacebocontrolledtrial AT jamesaplattsmills effectofscheduledantimicrobialandnicotinamidetreatmentonlineargrowthinchildreninruraltanzaniaafactorialrandomizeddoubleblindplacebocontrolledtrial AT saraheelwood effectofscheduledantimicrobialandnicotinamidetreatmentonlineargrowthinchildreninruraltanzaniaafactorialrandomizeddoubleblindplacebocontrolledtrial AT rebeccajscharf effectofscheduledantimicrobialandnicotinamidetreatmentonlineargrowthinchildreninruraltanzaniaafactorialrandomizeddoubleblindplacebocontrolledtrial AT joannmmcdermid effectofscheduledantimicrobialandnicotinamidetreatmentonlineargrowthinchildreninruraltanzaniaafactorialrandomizeddoubleblindplacebocontrolledtrial AT annewwanjuhi effectofscheduledantimicrobialandnicotinamidetreatmentonlineargrowthinchildreninruraltanzaniaafactorialrandomizeddoubleblindplacebocontrolledtrial AT samweljatosh effectofscheduledantimicrobialandnicotinamidetreatmentonlineargrowthinchildreninruraltanzaniaafactorialrandomizeddoubleblindplacebocontrolledtrial AT siphaelkatengu effectofscheduledantimicrobialandnicotinamidetreatmentonlineargrowthinchildreninruraltanzaniaafactorialrandomizeddoubleblindplacebocontrolledtrial AT tarinacparpia effectofscheduledantimicrobialandnicotinamidetreatmentonlineargrowthinchildreninruraltanzaniaafactorialrandomizeddoubleblindplacebocontrolledtrial AT elizabethtrogawskimcquade effectofscheduledantimicrobialandnicotinamidetreatmentonlineargrowthinchildreninruraltanzaniaafactorialrandomizeddoubleblindplacebocontrolledtrial AT jeangratz effectofscheduledantimicrobialandnicotinamidetreatmentonlineargrowthinchildreninruraltanzaniaafactorialrandomizeddoubleblindplacebocontrolledtrial AT erlingsvensen effectofscheduledantimicrobialandnicotinamidetreatmentonlineargrowthinchildreninruraltanzaniaafactorialrandomizeddoubleblindplacebocontrolledtrial AT jonathanrswann effectofscheduledantimicrobialandnicotinamidetreatmentonlineargrowthinchildreninruraltanzaniaafactorialrandomizeddoubleblindplacebocontrolledtrial AT jeffreyrdonowitz effectofscheduledantimicrobialandnicotinamidetreatmentonlineargrowthinchildreninruraltanzaniaafactorialrandomizeddoubleblindplacebocontrolledtrial AT paschalmdoe effectofscheduledantimicrobialandnicotinamidetreatmentonlineargrowthinchildreninruraltanzaniaafactorialrandomizeddoubleblindplacebocontrolledtrial AT sokoinekivuyo effectofscheduledantimicrobialandnicotinamidetreatmentonlineargrowthinchildreninruraltanzaniaafactorialrandomizeddoubleblindplacebocontrolledtrial AT ericrhoupt effectofscheduledantimicrobialandnicotinamidetreatmentonlineargrowthinchildreninruraltanzaniaafactorialrandomizeddoubleblindplacebocontrolledtrial AT estomihmduma effectofscheduledantimicrobialandnicotinamidetreatmentonlineargrowthinchildreninruraltanzaniaafactorialrandomizeddoubleblindplacebocontrolledtrial
_version_	1718375829934702592

Effect of scheduled antimicrobial and nicotinamide treatment on linear growth in children in rural Tanzania: A factorial randomized, double-blind, placebo-controlled trial.

Ejemplares similares