We aimed to systematically review evidence pertaining to the safety and efficacy of nitazoxanide in treating infectious diarrhea. On September 21, 2017, we identified relevant studies using 12 databases. The estimates of the included studies were pooled as a risk ratio (RR). We conducted a network and pairwise random-effects meta-analysis for both direct and indirect comparisons of different organisms that are known to cause diarrhea. The primary and secondary analysis outcomes were clinical response until cessation of illness, parasitological response and adverse events. We included 18 studies in our analysis. In cryptosporidiosis, the overall estimate favored nitazoxanide in its clinical response in comparison with placebo RR 1.46 [95% CI 1.22-1.74; P-value <0.0001]. Network meta-analysis among patients with Giardia intestinalis showed an increase in the probability of diarrheal cessation and parasitological responses in comparison with placebo, RR 1.69 [95% CI 1.08-2.64, P-score 0.27] and RR 2.91 [95% CI 1.72-4.91, P-score 0.55] respectively. In Clostridium difficile infection, the network meta-analysis revealed a non-significantly superior clinical response effect of nitazoxanide to metronidazole 31 days after treatment RR 1.21 [95% CI 0.87-1.69, P-score 0.26]. In Entamoeba histolytica, the overall estimate significantly favored nitazoxanide in parasitological response with placebo RR 1.80 [95% CI 1.35-2.40, P-value < 0.001]. We highlighted the effectiveness of nitazoxanide in the cessation of diarrhea caused by Cryptosporidium, Giardia intestinalis and Entamoeba histolytica infection. We also found significant superiority of NTZ to metronidazole in improving the clinical response to G. intestinalis, thus it may be a suitable candidate for treating infection-induced diarrhea. To prove the superiority of NTZ during a C. difficile infection may warrant a larger-scale clinical trial since its superiority was deemed insignificant. We recommend nitazoxanide as an appropriate option for treating infectious diarrhea.
Computational approaches to predict structure/function and other biological characteristics of proteins are becoming more common in comparison to the traditional methods in drug discovery. Cryptosporidiosis is a major zoonotic diarrheal disease particularly in children, which is caused primarily by Cryptosporidium hominis and Cryptosporidium parvum. Currently, there are no vaccines for cryptosporidiosis and recommended drugs are ineffective. With the availability of complete genome sequence of C. hominis, new targets have been recognized for the development of effective and better drugs and/or vaccines. We identified a unique hypothetical protein (TU502HP) in the C. hominis genome from the CryptoDB database. A three-dimensional model of the protein was generated using the Iterative Threading ASSEmbly Refinement server through an iterative threading method. Functional annotation and phylogenetic study of TU502HP protein revealed similarity with human transportin 3. The model is further subjected to a virtual screening study form the ZINC database compound library using the Dock Blaster server. A docking study through AutoDock software reported N-(3-chlorobenzyl)ethane-1,2-diamine as the best inhibitor in terms of docking score and binding energy. The reliability of the binding mode of the inhibitor is confirmed by a complex molecular dynamics simulation study using GROMACS software for 10 ns in the water environment. Furthermore, antigenic determinants of the protein were determined with the help of DNASTAR software. Our findings report a great potential in order to provide insights in the development of new drug(s) or vaccine(s) for treatment and prophylaxis of cryptosporidiosis among humans and animals.