Author:
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Liu L et al. Child Health Epidemiology Reference Group of WHO and UNICEF, 2012. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet 379: 2151–2161.
-
2.
GBD 2016 Diarrhoeal Disease Collaborators, 2018. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of diarrhoea in 195 countries: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Infect Dis 18: 1211–1228
-
3.
Richard SA et al. Childhood Malnutrition and Infection Network, 2014. Catch-up growth occurs after diarrhea in early childhood. J Nutr 144: 965–971.
-
4.
McCormick BJJ, Lang DR, 2016. Diarrheal disease and enteric infections in LMIC communities: how big is the problem? Trop Dis Travel Med Vaccines 2: 11.
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5.
Bhutta ZA, Nizami SQ, Isani Z, 1999. Zinc supplementation in malnourished children with persistent diarrhea in Pakistan. Pediatrics 103: e42.
-
6.
World Health Organization, 2005. The Treatment of Diarrhoea: A Manual for Physicians and Other Senior Health Workers. Geneva, Switzerland: WHO.
-
7.
Dangour AD, Watson L, Cumming O, Boisson S, Che Y, Velleman Y, Cavill S, Allen E, Uauy R, 2013. Interventions to improve water quality and supply, sanitation and hygiene practices, and their effects on the nutritional status of children. Cochrane Database Syst Rev 8: CD009382.
-
8.
Larsen DA, Grisham T, Slawsky E, Narine L, 2017. An individual-level meta-analysis assessing the impact of community-level sanitation access on child stunting, anemia, and diarrhea: evidence from DHS and MICS surveys. PLoS Negl Trop Dis 11: e0005591.
-
9.
Null C et al. 2018. Effects of water quality, sanitation, handwashing, and nutritional interventions on diarrhoea and child growth in rural Kenya: a cluster-randomised controlled trial. Lancet Glob Health 6: e316–e329.
-
10.
Luby SP et al. 2018. Effects of water quality, sanitation, handwashing, and nutritional interventions on diarrhoea and child growth in rural Bangladesh: a cluster randomised controlled trial. Lancet Glob Health 6: e302–e315.
-
11.
Stewart CP et al. 2018. Effects of water quality, sanitation, handwashing, and nutritional interventions on child development in rural Kenya (WASH benefits Kenya): a cluster-randomised controlled trial. Lancet Child Adolesc Health 2: 269–280.
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12.
Kotloff KL et al. 2013. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 382: 209–222.
-
13.
Platts-Mills JA et al. MAL-ED Network Investigators, 2015. Pathogen-specific burdens of community diarrhoea in developing countries: a multisite birth cohort study (MAL-ED). Lancet Glob Health 3: e564–575.
-
14.
Liu J et al. 2016. Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study. Lancet 388: 1291–1301.
-
15.
Pan American Health Organization, 2017. Health in the Americas: Children’s Health. Available at: https://www.paho.org/salud-en-las-americas-2017/?tag=infant-mortality. Accessed August 24, 2018.
-
16.
World Health Organization, 2018. Child Growth Standards: WHO Anthro (Version 3.2.2, January 2011) and Macros. Available at: https://www.who.int/childgrowth/software/en/. Accessed June 15, 2018.
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17.
Gaensbauer JT, Melgar MA, Calvimontes DM, Lamb MM, Asturias EJ, Contreras-Roldan IL, Dominguez SR, Robinson CC, Berman S, 2017. Efficacy of a bovine colostrum and egg-based intervention in acute childhood diarrhoea in Guatemala: a randomised, double-blind, placebo-controlled trial. BMJ Glob Health 2: e000452.
-
18.
Bruzzi P, Green SB, Byar DP, Brinton LA, Schairer C, 1985. Estimating the population attributable risk for multiple risk factors using case-control data. Am J Epidemiol 122: 904–914.
-
19.
Kamidani S, Melgar M, Robinson C, Asturias E, Berman S, Gaensbauer J, 2018. No detection of Entamoeba histolytica by multiplex polymerase chain reaction in children with acute non-bloody diarrhea in Guatemala. Pediatr Infect Dis J 37: e107–e108.
-
20.
Pelkonen T, Dos Santos MD, Roine I, Dos Anjos E, Freitas C, Peltola H, Laakso S, Kirveskari J, 2018. Potential diarrheal pathogens common also in healthy children in Angola. Pediatr Infect Dis J 37: 424–428.
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21.
Shen H et al. 2016. The 12 gastrointestinal pathogens spectrum of acute infectious diarrhea in a Sentinel Hospital, Shenzhen, China. Front Microbiol 7: 1926.
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22.
Adam MA, Wang J, Enan KA, Shen H, Wang H, El Hussein AR, Musa AB, Khidir IM, Ma X, 2018. Molecular survey of viral and bacterial causes of childhood diarrhea in Khartoum state, Sudan. Front Microbiol 9: 112.
-
23.
Moore SR, Lima NL, Soares AM, Oriá RB, Pinkerton RC, Barrett LJ, Guerrant RL, Lima AA, 2010. Prolonged episodes of acute diarrhea reduce growth and increase risk of persistent diarrhea in children. Gastroenterology 139: 1156–1164.
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24.
Schnee AE, Petri WA Jr., 2017. Campylobacter jejuni and associated immune mechanisms: short-term effects and long-term implications for infants in low-income countries. Curr Opin Infect Dis 30: 322–328.
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26.
Platts-Mills JA, Operario DJ, Houpt ER, 2012. Molecular diagnosis of diarrhea: current status and future potential. Curr Infect Dis Rep 14: 41–46.
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27.
Eibach D, Krumkamp R, Hahn A, Sarpong N, Adu-Sarkodie Y, Leva A, Käsmaier J, Panning M, May J, Tannich E, 2016. Application of a multiplex PCR assay for the detection of gastrointestinal pathogens in a rural African setting. BMC Infect Dis 16: 150.
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28.
de Boer RF, Ott A, Kesztyus B, Kooistra-Smid AM, 2010. Improved detection of five major gastrointestinal pathogens by use of a molecular screening approach. J Clin Microbiol 48: 4140–4146.
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29.
Platts-Mills JA et al. 2018. Use of quantitative molecular diagnostic methods to assess the aetiology, burden, and clinical characteristics of diarrhoea in children in low-resource settings: a reanalysis of the MAL-ED cohort study. Lancet Glob Health 6: e1309–e1318
-
30.
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31.
Watanabe K, Petri WA Jr., 2016. Environmental enteropathy: elusive but significant subclinical abnormalities in developing countries. EBioMedicine 10:25–32.
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World Health Organization, 2013. Essential Nutrition Actions: Improving Maternal, Newborn, Infant and Young Child Health and Nutrition. Geneva, Switzerland: WHO.
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33.
Riddle MS, Chen WH, Kirkwood CD, MacLennan CA, 2018. Update on vaccines for enteric pathogens. Clin Microbiol Infect 24: 1039–1045.
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34.
Holmgren J, Parashar UD, Plotkin S, Louis J, Ng SP, Desauziers E, Picot V, Saadatian-Elahi M, 2017. Correlates of protection for enteric vaccines. Vaccine 35: 3355–3363.
-
35.
Gaensbauer J, Melgar M, Lamb MM, Calvimontes DM, Asturias EJ, Contreras-Roldan I, Dominguez S, Robinson CC, Berman S, 2017. Efficacy of a novel nutritional product in acute childhood diarrhea in Guatemala: secondary and exploratory analyses of a randomized, double-blind, placebo-controlled trial. Open Forum Infect Dis 4: S117.
-
36.
Vega E, Barclay L, Gregoricus N, Shirley SH, Lee D, Vinjé J, 2014. Genotypic and epidemiologic trends of norovirus outbreaks in the United States, 2009 to 2013. J Clin Microbiol 52: 147–155.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 118 | 118 | 7 |
| Full Text Views | 1083 | 269 | 1 |
| PDF Downloads | 544 | 145 | 0 |
Identification of Enteropathogens by Multiplex PCR among Rural and Urban Guatemalan Children with Acute Diarrhea
James T. Gaensbauer
James T. Gaensbauer
Center for Global Health and Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado;
Department of Pediatrics, Denver Health Hospital Authority, Denver, Colorado;
Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado;
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Department of Pediatrics, Denver Health Hospital Authority, Denver, Colorado;
Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado;
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Molly Lamb
Molly Lamb
Center for Global Health and Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado;
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Diva M. Calvimontes
Diva M. Calvimontes
Hospital Roosevelt, Guatemala City, Guatemala;
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Edwin J. Asturias
Edwin J. Asturias
Center for Global Health and Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado;
Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado;
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Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado;
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Satoshi Kamidani
Satoshi Kamidani
Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado;
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Ingrid L. Contreras-Roldan
Ingrid L. Contreras-Roldan
Centro de Estudios en Salud, Universidad de Valle de Guatemala, Guatemala, Guatemala;
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Samuel R. Dominguez
Samuel R. Dominguez
Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado;
Department of Pathology and Laboratory Medicine, Children’s Hospital Colorado, Aurora, Colorado
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Department of Pathology and Laboratory Medicine, Children’s Hospital Colorado, Aurora, Colorado
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Christine C. Robinson
Christine C. Robinson
Department of Pathology and Laboratory Medicine, Children’s Hospital Colorado, Aurora, Colorado
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Alma Zacarias
Alma Zacarias
Center for Global Health and Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado;
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Stephen Berman
Stephen Berman
Center for Global Health and Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado;
Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado;
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Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado;
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Mario A. Melgar
Mario A. Melgar
Hospital Roosevelt, Guatemala City, Guatemala;
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Multiplex polymerase chain reaction (PCR) platforms have enhanced understanding of intestinal pathogens in low- and middle-income countries (LMICs). However, few such studies have been performed in Latin America, where poverty, poor sanitation, and undernutrition persist. Multiplex PCR (BioFire, Salt Lake City, UT) was used to identify viral, bacterial, and parasitic pathogens in stool collected on day 1 and 31 from children aged 6 to 35 months with acute, non-bloody diarrhea in two locations (rural and urban) in Guatemala. We analyzed correlation between pathogens and clinical, demographic, and socioeconomic variables; described patterns of pathogen acquisition, persistence, and clearance over the 30-day period; and calculated population attributable fractions (PAFs) for diarrheal causation for individual pathogens. We analyzed 316 subjects (144 urban; 172 rural) enrolled between March 2015 and January 2016. Rural subjects had significantly more malnutrition, animal exposure, and unimproved water/sanitation infrastructure. The majority of subjects had multiple pathogens/sample (4.8 rural and 2.7 urban). Few meaningful correlates were identified between individual pathogens and clinical, demographic, or environmental variables. Escherichia coli pathotypes, Shigella, Campylobacter, and Giardia had high rates of persistence between initial and 30-day follow-up. Statistically significant adjusted PAFs were identified for Campylobacter (14.9%, 95% CI: 3.2–23.1), norovirus (10.2%, 95% CI: 0.4–17.1), sapovirus (7.6%, 95% CI: 2.3–10.9), and adenovirus 40/41 (5.6%, 95% CI: 0.3–8.7). These observations further characterize the diversity and complexity of enteric pathogens in children in LMICs. Patterns of chronic symptomatic and asymptomatic infection among Latin American children are similar to those observed in other LMIC regions. Findings have direct implications for practitioners treating individuals with acute infectious diarrhea and should inform regional public health strategies.
- Supplemental Materials (PDF 218 KB)
Author Notes
Disclosure: E. J. A. reports grants from Pantheryx, G. S. K., and Pfizer outside the submitted work. S. B., I. L. C. R., J. T. G., M. L., and C. C. R., report grants from Pan Theryx, during the conduct of the study. M. A. M. reports personal fees from Fundacion para la salud integral de los guatemaltecos during the conduct of the study. S. R. D. reports grants from Biofire during the conduct of the study.
Financial support: Funding for the clinical trial from which data were obtained was provided by Pan Theryx, Inc., Boulder, CO. No funding was received for this analysis.
Authors’ addresses: James T. Gaensbauera, Center for Global Health and Department of Epidemiology, Colorado School of Public Health, Aurora, CO, Department of Pediatrics, Denver Health Hospital Authority, Denver, CO, and Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, E-mail: james.gaensbauer@dhha.org. Molly Lamb and Alma Zacarias, Center for Global Health and Department of Epidemiology, Colorado School of Public Health, Aurora, CO, E-mails: molly.lamb@cuanschutz.edu and almaloarca@yahoo.es. Diva M. Calvimontes and Mario A. Melgar, Hospital Roosevelt, Guatemala City, Guatemala, E-mails: mirellacalvimontes@yahoo.com and mariomelgart@gmail.com. Edwin J. Asturias and Stephen Berman, Center for Global Health and Department of Epidemiology, Colorado School of Public Health, Aurora, CO, and Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, E-mails: edwin.asturias@childrenscolorado.org and stephen.berman@childrenscolorado.org. Satoshi Kamidani, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, E-mail: satoshi.kamidani@emory.edu. Ingrid L. Contreras-Roldan, Centro de Estudios en Salud, Universidad de Valle de Guatemala, Guatemala, Guatemala, E-mail: icontreras@ces.uvg.edu.gt. Samuel R. Dominguez, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, and Department of Pathology and Laboratory Medicine, Children’s Hospital Colorado, Aurora, CO, E-mail: samuel.dominguez@childrenscolorado.org. Christine C. Robinson, Department of Pathology and Laboratory Medicine, Children’s Hospital Colorado, Aurora, CO, E-mail: christine.robinson@childrenscolorado.org.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Liu L et al. Child Health Epidemiology Reference Group of WHO and UNICEF, 2012. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet 379: 2151–2161.
-
2.
GBD 2016 Diarrhoeal Disease Collaborators, 2018. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of diarrhoea in 195 countries: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Infect Dis 18: 1211–1228
-
3.
Richard SA et al. Childhood Malnutrition and Infection Network, 2014. Catch-up growth occurs after diarrhea in early childhood. J Nutr 144: 965–971.
-
4.
McCormick BJJ, Lang DR, 2016. Diarrheal disease and enteric infections in LMIC communities: how big is the problem? Trop Dis Travel Med Vaccines 2: 11.
-
5.
Bhutta ZA, Nizami SQ, Isani Z, 1999. Zinc supplementation in malnourished children with persistent diarrhea in Pakistan. Pediatrics 103: e42.
-
6.
World Health Organization, 2005. The Treatment of Diarrhoea: A Manual for Physicians and Other Senior Health Workers. Geneva, Switzerland: WHO.
-
7.
Dangour AD, Watson L, Cumming O, Boisson S, Che Y, Velleman Y, Cavill S, Allen E, Uauy R, 2013. Interventions to improve water quality and supply, sanitation and hygiene practices, and their effects on the nutritional status of children. Cochrane Database Syst Rev 8: CD009382.
-
8.
Larsen DA, Grisham T, Slawsky E, Narine L, 2017. An individual-level meta-analysis assessing the impact of community-level sanitation access on child stunting, anemia, and diarrhea: evidence from DHS and MICS surveys. PLoS Negl Trop Dis 11: e0005591.
-
9.
Null C et al. 2018. Effects of water quality, sanitation, handwashing, and nutritional interventions on diarrhoea and child growth in rural Kenya: a cluster-randomised controlled trial. Lancet Glob Health 6: e316–e329.
-
10.
Luby SP et al. 2018. Effects of water quality, sanitation, handwashing, and nutritional interventions on diarrhoea and child growth in rural Bangladesh: a cluster randomised controlled trial. Lancet Glob Health 6: e302–e315.
-
11.
Stewart CP et al. 2018. Effects of water quality, sanitation, handwashing, and nutritional interventions on child development in rural Kenya (WASH benefits Kenya): a cluster-randomised controlled trial. Lancet Child Adolesc Health 2: 269–280.
-
12.
Kotloff KL et al. 2013. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 382: 209–222.
-
13.
Platts-Mills JA et al. MAL-ED Network Investigators, 2015. Pathogen-specific burdens of community diarrhoea in developing countries: a multisite birth cohort study (MAL-ED). Lancet Glob Health 3: e564–575.
-
14.
Liu J et al. 2016. Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study. Lancet 388: 1291–1301.
-
15.
Pan American Health Organization, 2017. Health in the Americas: Children’s Health. Available at: https://www.paho.org/salud-en-las-americas-2017/?tag=infant-mortality. Accessed August 24, 2018.
-
16.
World Health Organization, 2018. Child Growth Standards: WHO Anthro (Version 3.2.2, January 2011) and Macros. Available at: https://www.who.int/childgrowth/software/en/. Accessed June 15, 2018.
-
17.
Gaensbauer JT, Melgar MA, Calvimontes DM, Lamb MM, Asturias EJ, Contreras-Roldan IL, Dominguez SR, Robinson CC, Berman S, 2017. Efficacy of a bovine colostrum and egg-based intervention in acute childhood diarrhoea in Guatemala: a randomised, double-blind, placebo-controlled trial. BMJ Glob Health 2: e000452.
-
18.
Bruzzi P, Green SB, Byar DP, Brinton LA, Schairer C, 1985. Estimating the population attributable risk for multiple risk factors using case-control data. Am J Epidemiol 122: 904–914.
-
19.
Kamidani S, Melgar M, Robinson C, Asturias E, Berman S, Gaensbauer J, 2018. No detection of Entamoeba histolytica by multiplex polymerase chain reaction in children with acute non-bloody diarrhea in Guatemala. Pediatr Infect Dis J 37: e107–e108.
-
20.
Pelkonen T, Dos Santos MD, Roine I, Dos Anjos E, Freitas C, Peltola H, Laakso S, Kirveskari J, 2018. Potential diarrheal pathogens common also in healthy children in Angola. Pediatr Infect Dis J 37: 424–428.
-
21.
Shen H et al. 2016. The 12 gastrointestinal pathogens spectrum of acute infectious diarrhea in a Sentinel Hospital, Shenzhen, China. Front Microbiol 7: 1926.
-
22.
Adam MA, Wang J, Enan KA, Shen H, Wang H, El Hussein AR, Musa AB, Khidir IM, Ma X, 2018. Molecular survey of viral and bacterial causes of childhood diarrhea in Khartoum state, Sudan. Front Microbiol 9: 112.
-
23.
Moore SR, Lima NL, Soares AM, Oriá RB, Pinkerton RC, Barrett LJ, Guerrant RL, Lima AA, 2010. Prolonged episodes of acute diarrhea reduce growth and increase risk of persistent diarrhea in children. Gastroenterology 139: 1156–1164.
-
24.
Schnee AE, Petri WA Jr., 2017. Campylobacter jejuni and associated immune mechanisms: short-term effects and long-term implications for infants in low-income countries. Curr Opin Infect Dis 30: 322–328.
-
25.
Bartelt LA, Sartor RB, 2015. Advances in understanding Giardia: determinants and mechanisms of chronic sequelae. F1000Prime Rep 7: 62.
-
26.
Platts-Mills JA, Operario DJ, Houpt ER, 2012. Molecular diagnosis of diarrhea: current status and future potential. Curr Infect Dis Rep 14: 41–46.
-
27.
Eibach D, Krumkamp R, Hahn A, Sarpong N, Adu-Sarkodie Y, Leva A, Käsmaier J, Panning M, May J, Tannich E, 2016. Application of a multiplex PCR assay for the detection of gastrointestinal pathogens in a rural African setting. BMC Infect Dis 16: 150.
-
28.
de Boer RF, Ott A, Kesztyus B, Kooistra-Smid AM, 2010. Improved detection of five major gastrointestinal pathogens by use of a molecular screening approach. J Clin Microbiol 48: 4140–4146.
-
29.
Platts-Mills JA et al. 2018. Use of quantitative molecular diagnostic methods to assess the aetiology, burden, and clinical characteristics of diarrhoea in children in low-resource settings: a reanalysis of the MAL-ED cohort study. Lancet Glob Health 6: e1309–e1318
-
30.
Liu J et al. 2014. Development and assessment of molecular diagnostic tests for 15 enteropathogens causing childhood diarrhoea: a multicenter study. Lancet Infect Dis 14: 716–724
-
31.
Watanabe K, Petri WA Jr., 2016. Environmental enteropathy: elusive but significant subclinical abnormalities in developing countries. EBioMedicine 10:25–32.
-
32.
World Health Organization, 2013. Essential Nutrition Actions: Improving Maternal, Newborn, Infant and Young Child Health and Nutrition. Geneva, Switzerland: WHO.
-
33.
Riddle MS, Chen WH, Kirkwood CD, MacLennan CA, 2018. Update on vaccines for enteric pathogens. Clin Microbiol Infect 24: 1039–1045.
-
34.
Holmgren J, Parashar UD, Plotkin S, Louis J, Ng SP, Desauziers E, Picot V, Saadatian-Elahi M, 2017. Correlates of protection for enteric vaccines. Vaccine 35: 3355–3363.
-
35.
Gaensbauer J, Melgar M, Lamb MM, Calvimontes DM, Asturias EJ, Contreras-Roldan I, Dominguez S, Robinson CC, Berman S, 2017. Efficacy of a novel nutritional product in acute childhood diarrhea in Guatemala: secondary and exploratory analyses of a randomized, double-blind, placebo-controlled trial. Open Forum Infect Dis 4: S117.
-
36.
Vega E, Barclay L, Gregoricus N, Shirley SH, Lee D, Vinjé J, 2014. Genotypic and epidemiologic trends of norovirus outbreaks in the United States, 2009 to 2013. J Clin Microbiol 52: 147–155.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 118 | 118 | 7 |
| Full Text Views | 1083 | 269 | 1 |
| PDF Downloads | 544 | 145 | 0 |