Effect of Nitazoxanide and Probiotic Treatment on Bangladeshi Children with Cryptosporidiosis

Zannatun Noor Infectious Diseases Division, International Centre for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh;

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Biplob Hossain Infectious Diseases Division, International Centre for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh;

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Nishad Tasnim Mithila Nutrition Research Division, International Centre for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh;

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Amena Khatun Infectious Diseases Division, International Centre for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh;

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Sultan Mahmud Infectious Diseases Division, International Centre for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh;

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Aleya Ferdous Infectious Diseases Division, International Centre for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh;

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Bipasha Akhter North South University Genome Research Institute, Dhaka, Bangladesh;

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Masud Alam Department of Molecular Genetics and Microbiology, Vaccine Testing Center, University of Vermont, Burlington, Vermont;

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Carol A. Gilchrist Department of Medicine, University of Virginia, Charlottesville, Virginia

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Rashidul Haque Infectious Diseases Division, International Centre for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh;

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William A. Petri Department of Medicine, University of Virginia, Charlottesville, Virginia

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Cryptosporidium spp. is a cause of diarrhea morbidity and mortality in children under 5 years of age. In addition, asymptomatic infections can have a negative impact on growth and development. In low- and middle-income countries where a greater number of infants may be malnourished, the results of treating cryptosporidiosis with the only Food and Drug Administration-approved drug nitazoxanide (NTZ) have been inconsistent. Malnutrition is both a risk factor for cryptosporidiosis and a consequence of infection with this parasite. Treatment with the probiotic Lactobacillus reuteri DSM 17938 has been shown to assist in nutritional recovery and the restoration of gut health. In this pilot randomized clinical trial, we examined whether combined probiotic and NTZ treatment could result in the reduction in parasitemia and infection-associated growth stunting in undernourished children. Cryptosporidium spp.-positive Bangladeshi children with a weight-for-length Z score between −1 and −3 were randomly assigned to one of three groups. Group 1 (n = 26) received NTZ and Lactobacillus, group 2 (n = 28) received NTZ along with a placebo, and the third control group (n = 10) received standard care. There was no difference in the duration of infection or improvement in child anthropometric measurements in any treatment group compared with control. Therefore, this pilot study does not provide support for treatment with NTZ, Lactobacillus, or the two in combination as an effective means of reducing the duration of Cryptosporidium spp. infection or improving growth in growth-stunted children.

Author Notes

Financial support: This work was supported by an Early Career Award from the Thrasher Research Fund (Grant no. 15173) and the National Institute of Allergy and Infectious Diseases (Grant no. AI043596). The funders had no role in study design, data collection and analysis, or the decision to submit for publication.

Disclosures: We declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. W. A. Petri is a consultant for TechLab, a company that makes diagnostic tests for cryptosporidiosis. The study was approved (PR-19079) by the Ethical and Research Review Committees of the International Centre for Diarrheal Disease Research, Bangladesh. Informed written consent was obtained from the parents or guardians for the participation of their child in the study.

Authors’ contributions: Z. Noor, R. Haque, and W. A. Petri conceived the study. Drafting of the manuscript was performed by Z. Noor and B. Hossain. Clinical fieldwork and data collection were performed by B. Akhter and M. Alam, with supervision from Z. Noor and R. Haque. N. T. Mithila, A. Khatun, and S. Mahmud performed the laboratory experiments. A. Ferdous maintained the study database. Z. Noor, B. Hossain, and A. Ferdous preformed the data analyses. C. A. Gilchrist and R. Haque reviewed the first draft manuscript, suggested additional analysis, and provided additional comments. W. A. Petri reviewed the final draft of the manuscript and provided critical comments. All authors edited and approved the final manuscript. Z. Noor finalized the manuscript, which was subsequently approved by all authors.

Current contact information: Zannatun Noor, Biplob Hossain, Amena Khatun, Sultan Mahmud, Aleya Ferdous, and Rashidul Haque, Infectious Diseases Division, International Centre for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh, E-mails: zannatun@icddrb.org, bhossain@icddrb.org, amena.khatun@icddrb.org, smahmud@icddrb.org, aferdous@icddrb.org, and rhaque@icddrb.org. Nishad Tasnim Mithila, Nutrition Research Division, International Centre for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh, E-mail: nishad.mithila@icddrb.org. Bipasha Akhter, North South University Genome Research Institute, Dhaka, Bangladesh, E-mail: dr.bipasha.akhter@gmail.com. Masud Alam, Department of Molecular Genetics and Microbiology, Vaccine Testing Center, University of Vermont, Burlington, VT, E-mail: mohammad-masud.alam@med.uvm.edu. Carol A. Gilchrist and William A. Petri, Department of Medicine, University of Virginia, Charlottesville, VA, E-mails: cg2p@virginia.edu and wap3g@virginia.edu.

Address correspondence to Zannatun Noor, Enteric and Respiratory Infection, Emerging Infections and Parasitology Laboratory, IDD, International Centre for Diarrheal Disease Research, Bangladesh, 68, Shahid Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212, Bangladesh. E-mail: zannatun@icddrb.org
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