Walker CL, Aryee MJ, Boschi-Pinto C, Black RE, 2012. Estimating diarrhea mortality among young children in low and middle income countries. PLoS One 7: e29151.
Bern C, Martines J, de Zoysa I, Glass RI, 1992. The magnitude of the global problem of diarrhoeal disease: a ten-year update. Bull World Health Organ 70: 705–714.
Albert MJ, Faruque AS, Faruque SM, Sack RB, Mahalanabis D, 1999. Case-control study of enteropathogens associated with childhood diarrhea in Dhaka, Bangladesh. J Clin Microbiol 37: 3458–3464.
Levine MM, Robins-Browne RM, 2012. Factors that explain excretion of enteric pathogens by persons without diarrhea. Clin Infect Dis 55: S303–S311.
Panchalingam S, Antonio M, Hossain A, Mandomando I, Ochieng B, Oundo J, Ramamurthy T, Tamboura B, Zaidi AKM, Petri W, Houpt E, Murray P, Prado V, Vidal R, Steele D, Strockbine N, Sansonetti P, Glass RI, Robins-Browne RM, Tauschek M, Svennerholm A-M, Kotloff K, Levine MM, Nataro JP, 2012. Diagnostic microbiologic methods in the GEMS-1 case/control study. Clin Infect Dis 55: S294–S302.
Amar CF, East CL, Gray J, Iturriza-Gomara M, Maclure EA, McLauchlin J, 2007. Detection by PCR of eight groups of enteric pathogens in 4,627 faecal samples: re-examination of the English case-control Infectious Intestinal Disease Study (1993–1996). Eur J Clin Microbiol Infect Dis 26: 311–323.
Liu J, Gratz J, Amour C, Kibiki G, Becker S, Janaki L, Verweij JJ, Taniuchi M, Sobuz SU, Haque R, Haverstick DM, Houpt ER, 2013. A laboratory-developed TaqMan Array Card for simultaneous detection of 19 enteropathogens. J Clin Microbiol 51: 472–480.
Kang G, Iturriza-Gomara M, Wheeler JG, Crystal P, Monica B, Ramani S, Primrose B, Moses PD, Gallimore CI, Brown DW, Gray J, 2004. Quantitation of group A rotavirus by real-time reverse-transcription-polymerase chain reaction: correlation with clinical severity in children in South India. J Med Virol 73: 118–122.
Barletta F, Ochoa TJ, Mercado E, Ruiz J, Ecker L, Lopez G, Mispireta M, Gil AI, Lanata CF, Cleary TG, 2011. Quantitative real-time polymerase chain reaction for enteropathogenic Escherichia coli: a tool for investigation of asymptomatic versus symptomatic infections. Clin Infect Dis 53: 1223–1229.
Lindsay B, Ochieng JB, Ikumapayi UN, Toure A, Ahmed D, Li S, Panchalingam S, Levine MM, Kotloff K, Rasko DA, Morris CR, Juma J, Fields BS, Dione M, Malle D, Becker SM, Houpt ER, Nataro JP, Sommerfelt H, Pop M, Oundo J, Antonio M, Hossain A, Tamboura B, Stine OC, 2013. Quantitative PCR for detection of Shigella improves ascertainment of Shigella burden in children with moderate-to-severe diarrhea in low-income countries. J Clin Microbiol 51: 1740–1746.
Phillips G, Lopman B, Tam C, Iturriza-Gomara M, Brown D, Gray J, 2009. Diagnosing norovirus-associated infectious intestinal disease using viral load. BMC Infect Dis 9: 63.
Group WHOMGRS, 2006. WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr Suppl 450: 76–85.
Haque R, Roy S, Siddique A, Mondal U, Rahman SM, Mondal D, Houpt E, Petri WA Jr, 2007. Multiplex real-time PCR assay for detection of Entamoeba histolytica, Giardia intestinalis, and Cryptosporidium spp. Am J Trop Med Hyg 76: 713–717.
Taniuchi M, Verweij JJ, Noor Z, Sobuz SU, Lieshout L, Petri WA Jr, Haque R, Houpt ER, 2011. High throughput multiplex PCR and probe-based detection with Luminex beads for seven intestinal parasites. Am J Trop Med Hyg 84: 332–337.
Liu J, Kibiki G, Maro V, Maro A, Kumburu H, Swai N, Taniuchi M, Gratz J, Toney D, Kang G, Houpt E, 2011. Multiplex reverse transcription PCR Luminex assay for detection and quantitation of viral agents of gastroenteritis. J Clin Virol 50: 308–313.
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.
Hooton TM, Bradley SF, Cardenas DD, Colgan R, Geerlings SE, Rice JC, Saint S, Schaeffer AJ, Tambayh PA, Tenke P, Nicolle LE, 2010. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis 50: 625–663.
Fujisawa T, Suda T, Matsuda H, Inui N, Nakamura Y, Sato J, Toyoshima M, Nakano Y, Yasuda K, Gemma H, Hayakawa H, Chida K, 2009. Real-time PCR is more specific than conventional PCR for induced sputum diagnosis of Pneumocystis pneumonia in immunocompromised patients without HIV infection. Respirology 14: 203–209.
Robins-Browne RM, Levine MM, 2012. Laboratory diagnostic challenges in case/control studies of diarrhea in developing countries. Clin Infect Dis 55: S312–S316.
Chappell CL, Okhuysen PC, Sterling CR, DuPont HL, 1996. Cryptosporidium parvum: intensity of infection and oocyst excretion patterns in healthy volunteers. J Infect Dis 173: 232–236.
Atmar R, Opekun A, Gilger M, Estes M, Crawford S, Neill F, 2008. Norwalk virus shedding after experimental human infection. Emerg Infect Dis 14: 1553–1557.
Ng CT, Gilchrist CA, Lane A, Roy S, Haque R, Houpt ER, 2005. Multiplex real-time PCR assay using Scorpion probes and DNA capture for genotype-specific detection of Giardia lamblia on fecal samples. J Clin Microbiol 43: 1256–1260.
Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, Wu Y, Sow SO, Sur D, Breiman RF, Faruque AS, Zaidi AK, Saha D, Alonso PL, Tamboura B, Sanogo D, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Ochieng JB, Omore R, Oundo JO, Hossain A, Das SK, Ahmed S, Qureshi S, Quadri F, Adegbola RA, Antonio M, Hossain MJ, Akinsola A, Mandomando I, Nhampossa T, Acacio S, Biswas K, O'Reilly CE, Mintz ED, Berkeley LY, Muhsen K, Sommerfelt H, Robins-Browne RM, Levine MM, 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.
Moyo SJ, Gro N, Kirsti V, Matee MI, Kitundu J, Maselle SY, Langeland N, Myrmel H, 2007. Prevalence of enteropathogenic viruses and molecular characterization of group A rotavirus among children with diarrhea in Dar es Salaam Tanzania. BMC Public Health 7: 359.
Naficy AB, Rao MR, Holmes JL, Abu-Elyazeed R, Savarino SJ, Wierzba TF, Frenck RW, Monroe SS, Glass RI, Clemens JD, 2000. Astrovirus diarrhea in Egyptian children. J Infect Dis 182: 685–690.
Black RE, Brown KH, Becker S, 1984. Effects of diarrhea associated with specific enteropathogens on the growth of children in rural Bangladesh. Pediatrics 73: 799–805.
Mondal D, Minak J, Alam M, Liu Y, Dai J, Korpe P, Liu L, Haque R, Petri WA Jr, 2012. Contribution of enteric infection, altered intestinal barrier function, and maternal malnutrition to infant malnutrition in Bangladesh. Clin Infect Dis 54: 185–192.
Lee G, Pan W, Penataro Yori P, Paredes Olortegui M, Tilley D, Gregory M, Oberhelman R, Burga R, Chavez CB, Kosek M, 2013. Symptomatic and asymptomatic Campylobacter infections associated with reduced growth in Peruvian children. PLoS Negl Trop Dis 7: e2036.
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Etiologic studies of diarrhea are limited by uneven diagnostic methods and frequent asymptomatic detection of enteropathogens. Polymerase chain reaction-based stool pathogen quantification may help distinguish clinically significant infections. We performed a nested case-control study of diarrhea in infants from a community-based birth cohort in Tanzania. We tested 71 diarrheal samples and pre-diarrheal matched controls with a laboratory-developed TaqMan Array Card for 19 enteropathogens. With qualitative detection, no pathogens were significantly associated with diarrhea. When pathogen quantity was considered, rotavirus (odds ratio [OR] = 2.70 per log10 increase, P < 0.001), astrovirus (OR = 1.49, P = 0.01), and Shigella/enteroinvasive Escherichia coli (OR = 1.47, P = 0.04) were associated with diarrhea. Enterotoxigenic E. coli (0.15 SD decline in length-for-age z score after 3 months per log10 increase, P < 0.001) and Campylobacter jejuni/C. coli (0.11 SD decline, P = 0.003) in pre-diarrheal stools were associated with poor linear growth. Quantitative analysis can help refine the association between enteropathogens and disease in endemic settings.
Financial support: This work was supported by National Institute of Allergy and Infectious Diseases, National Institutes of Health Grant U01 AI075396 and Bill & Melinda Gates Foundation Global Health Grant OPP1019093 (to E.R.H.).
Authors' addresses: James A. Platts-Mills, Jean Gratz, Jie Liu, and Eric R. Houpt, Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, VA, E-mails: jp5t@virginia.edu, jean.gratz@gmail.com, jl5yj@virginia.edu, and erh6k@virginia.edu. Esto Mduma, Erling Svensen, and Caroline Amour, Haydom Lutheran Hospital, Haydom, Tanzania, E-mails: estomih.mduma@haydom.co.tz, erling.svensen@cih.uib.no, and lyneamour@gmail.com. Athanasia Maro, Queen Saidi, Ndealilia Swai, Happiness Kumburu, and Gibson Kibiki, Kilimanjaro Clinical Research Institute, Moshi, Tanzania, E-mails: athanasia.maro@gmail.com, queensaidi@gmail.com, lilia2005tz@yahoo.co.uk, hk9s@virginia.edu, and g.kibiki@kcri.ac.tz. Benjamin J. J. McCormick, Fogarty International Center, National Institutes of Health, Bethesda, MD, E-mail: ben.mccormick@gmail.com.
Walker CL, Aryee MJ, Boschi-Pinto C, Black RE, 2012. Estimating diarrhea mortality among young children in low and middle income countries. PLoS One 7: e29151.
Bern C, Martines J, de Zoysa I, Glass RI, 1992. The magnitude of the global problem of diarrhoeal disease: a ten-year update. Bull World Health Organ 70: 705–714.
Albert MJ, Faruque AS, Faruque SM, Sack RB, Mahalanabis D, 1999. Case-control study of enteropathogens associated with childhood diarrhea in Dhaka, Bangladesh. J Clin Microbiol 37: 3458–3464.
Levine MM, Robins-Browne RM, 2012. Factors that explain excretion of enteric pathogens by persons without diarrhea. Clin Infect Dis 55: S303–S311.
Panchalingam S, Antonio M, Hossain A, Mandomando I, Ochieng B, Oundo J, Ramamurthy T, Tamboura B, Zaidi AKM, Petri W, Houpt E, Murray P, Prado V, Vidal R, Steele D, Strockbine N, Sansonetti P, Glass RI, Robins-Browne RM, Tauschek M, Svennerholm A-M, Kotloff K, Levine MM, Nataro JP, 2012. Diagnostic microbiologic methods in the GEMS-1 case/control study. Clin Infect Dis 55: S294–S302.
Amar CF, East CL, Gray J, Iturriza-Gomara M, Maclure EA, McLauchlin J, 2007. Detection by PCR of eight groups of enteric pathogens in 4,627 faecal samples: re-examination of the English case-control Infectious Intestinal Disease Study (1993–1996). Eur J Clin Microbiol Infect Dis 26: 311–323.
Liu J, Gratz J, Amour C, Kibiki G, Becker S, Janaki L, Verweij JJ, Taniuchi M, Sobuz SU, Haque R, Haverstick DM, Houpt ER, 2013. A laboratory-developed TaqMan Array Card for simultaneous detection of 19 enteropathogens. J Clin Microbiol 51: 472–480.
Kang G, Iturriza-Gomara M, Wheeler JG, Crystal P, Monica B, Ramani S, Primrose B, Moses PD, Gallimore CI, Brown DW, Gray J, 2004. Quantitation of group A rotavirus by real-time reverse-transcription-polymerase chain reaction: correlation with clinical severity in children in South India. J Med Virol 73: 118–122.
Barletta F, Ochoa TJ, Mercado E, Ruiz J, Ecker L, Lopez G, Mispireta M, Gil AI, Lanata CF, Cleary TG, 2011. Quantitative real-time polymerase chain reaction for enteropathogenic Escherichia coli: a tool for investigation of asymptomatic versus symptomatic infections. Clin Infect Dis 53: 1223–1229.
Lindsay B, Ochieng JB, Ikumapayi UN, Toure A, Ahmed D, Li S, Panchalingam S, Levine MM, Kotloff K, Rasko DA, Morris CR, Juma J, Fields BS, Dione M, Malle D, Becker SM, Houpt ER, Nataro JP, Sommerfelt H, Pop M, Oundo J, Antonio M, Hossain A, Tamboura B, Stine OC, 2013. Quantitative PCR for detection of Shigella improves ascertainment of Shigella burden in children with moderate-to-severe diarrhea in low-income countries. J Clin Microbiol 51: 1740–1746.
Phillips G, Lopman B, Tam C, Iturriza-Gomara M, Brown D, Gray J, 2009. Diagnosing norovirus-associated infectious intestinal disease using viral load. BMC Infect Dis 9: 63.
Group WHOMGRS, 2006. WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr Suppl 450: 76–85.
Haque R, Roy S, Siddique A, Mondal U, Rahman SM, Mondal D, Houpt E, Petri WA Jr, 2007. Multiplex real-time PCR assay for detection of Entamoeba histolytica, Giardia intestinalis, and Cryptosporidium spp. Am J Trop Med Hyg 76: 713–717.
Taniuchi M, Verweij JJ, Noor Z, Sobuz SU, Lieshout L, Petri WA Jr, Haque R, Houpt ER, 2011. High throughput multiplex PCR and probe-based detection with Luminex beads for seven intestinal parasites. Am J Trop Med Hyg 84: 332–337.
Liu J, Kibiki G, Maro V, Maro A, Kumburu H, Swai N, Taniuchi M, Gratz J, Toney D, Kang G, Houpt E, 2011. Multiplex reverse transcription PCR Luminex assay for detection and quantitation of viral agents of gastroenteritis. J Clin Virol 50: 308–313.
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.
Hooton TM, Bradley SF, Cardenas DD, Colgan R, Geerlings SE, Rice JC, Saint S, Schaeffer AJ, Tambayh PA, Tenke P, Nicolle LE, 2010. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis 50: 625–663.
Fujisawa T, Suda T, Matsuda H, Inui N, Nakamura Y, Sato J, Toyoshima M, Nakano Y, Yasuda K, Gemma H, Hayakawa H, Chida K, 2009. Real-time PCR is more specific than conventional PCR for induced sputum diagnosis of Pneumocystis pneumonia in immunocompromised patients without HIV infection. Respirology 14: 203–209.
Robins-Browne RM, Levine MM, 2012. Laboratory diagnostic challenges in case/control studies of diarrhea in developing countries. Clin Infect Dis 55: S312–S316.
Chappell CL, Okhuysen PC, Sterling CR, DuPont HL, 1996. Cryptosporidium parvum: intensity of infection and oocyst excretion patterns in healthy volunteers. J Infect Dis 173: 232–236.
Atmar R, Opekun A, Gilger M, Estes M, Crawford S, Neill F, 2008. Norwalk virus shedding after experimental human infection. Emerg Infect Dis 14: 1553–1557.
Ng CT, Gilchrist CA, Lane A, Roy S, Haque R, Houpt ER, 2005. Multiplex real-time PCR assay using Scorpion probes and DNA capture for genotype-specific detection of Giardia lamblia on fecal samples. J Clin Microbiol 43: 1256–1260.
Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, Wu Y, Sow SO, Sur D, Breiman RF, Faruque AS, Zaidi AK, Saha D, Alonso PL, Tamboura B, Sanogo D, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Ochieng JB, Omore R, Oundo JO, Hossain A, Das SK, Ahmed S, Qureshi S, Quadri F, Adegbola RA, Antonio M, Hossain MJ, Akinsola A, Mandomando I, Nhampossa T, Acacio S, Biswas K, O'Reilly CE, Mintz ED, Berkeley LY, Muhsen K, Sommerfelt H, Robins-Browne RM, Levine MM, 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.
Moyo SJ, Gro N, Kirsti V, Matee MI, Kitundu J, Maselle SY, Langeland N, Myrmel H, 2007. Prevalence of enteropathogenic viruses and molecular characterization of group A rotavirus among children with diarrhea in Dar es Salaam Tanzania. BMC Public Health 7: 359.
Naficy AB, Rao MR, Holmes JL, Abu-Elyazeed R, Savarino SJ, Wierzba TF, Frenck RW, Monroe SS, Glass RI, Clemens JD, 2000. Astrovirus diarrhea in Egyptian children. J Infect Dis 182: 685–690.
Black RE, Brown KH, Becker S, 1984. Effects of diarrhea associated with specific enteropathogens on the growth of children in rural Bangladesh. Pediatrics 73: 799–805.
Mondal D, Minak J, Alam M, Liu Y, Dai J, Korpe P, Liu L, Haque R, Petri WA Jr, 2012. Contribution of enteric infection, altered intestinal barrier function, and maternal malnutrition to infant malnutrition in Bangladesh. Clin Infect Dis 54: 185–192.
Lee G, Pan W, Penataro Yori P, Paredes Olortegui M, Tilley D, Gregory M, Oberhelman R, Burga R, Chavez CB, Kosek M, 2013. Symptomatic and asymptomatic Campylobacter infections associated with reduced growth in Peruvian children. PLoS Negl Trop Dis 7: e2036.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 1130 | 893 | 28 |
Full Text Views | 621 | 25 | 0 |
PDF Downloads | 186 | 22 | 0 |