Effect of Nitazoxanide and Probiotic Treatment on Bangladeshi Children with Cryptosporidiosis

Abstract

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.

Figure 1.

The study design flowchart shows the details of the randomized, controlled trial. NTZ = nitazoxanide.

Figure 2.

Cryptosporidium spp. infection prevalence. This was assessed using (A) QUIK CHEK, (B) ELISA, and (C) quantitative polymerase chain reaction (qPCR) techniques on days 4, 8, and 20 after enrollment. The y axes indicate the probability of remaining infected; the x axes indicate the days since the initial positive stool sample was collected. Lines represent the probability of remaining infected over time in the different groups: nitazoxanide (NTZ) plus probiotic (green lines), NTZ plus placebo (red lines), and control (black lines). The P-value for the difference between groups was determined by use of the log-rank (Mantel–Cox) test, and none of the comparisons between groups met our criteria to be considered significant (P ≤0.05). n.s. = not significant.

Figure 3.

Relative change in parasite burden in the infected children over time. Impact of the different treatment regimens on parasite burden are measured by (A) diagnostic quantitative polymerase chain reaction (qPCR; the y axis indicates quantitative cycle [Cq]) and (B) Cryptosporidium antigen (the y axis indicates relative antigen levels). In both A and B, the x axes indicate the time in days since the child was enrolled; at each time point, each symbol represents the value obtained from an individual child, and the line represents the linear relationship between the parasite burden and the time infected in each group (simple linear regression): nitazoxanide (NTZ) plus probiotic (green symbols and lines), NTZ plus placebo (red symbols and lines), and controls (black symbols and lines). There were no significant differences in either the elevation or slope between any of the groups as assessed by linear regression.