Cryptosporidium parvum is a protozoan parasite can affect humans, worldwide, causing asymptomatic infections or diarrheal disease, which may be life-threatening in immunocompromised and neonatal individuals. Mefloquine is one of the most promising anti-parasitic drugs. The present report aimed to study the in-vivo efficacy of Mefloquine when applied inimmunocompetent and immunocompromised cryptosporidiosis-infected mice groups, each of the them was subclassified into the following groups :non-infected non-treated group (normal control), infected non-treated group (infected control), nitazoxanide treated group and Mefloquine treated group. One week post infection, treated groups received either Nitazoxanide (100mg\Kg daily for 5 days) or single dose of Mefloquine (400mg/ Kg). Two weeks post treatment, all mice were scarified. Stool samples and intestinal histopathological specimens were examined. For both drugs, immunocompetent groups showed better parasitological clearance than immunocomporomized one. Cryptosporidium oocyst reduction rates with Nitazoxanide (NTZ) and Mefloquine were 53.3%, and 61.6% respectively in the immunocompetent groups. The corresponding rates in immunocompromised groups were 49.93% and 60.03%.for NTZ and Mefloquine respectively. A single dose of Mefloquine treatment (400mg/kg) resulted in higher oocyst reduction rates than the approved anti-cryptosporidiosis drug (Nitazoxanide with five days application regimen). The histopathological study supported the parasitological findings as mefloquine treated mice tissue showed mild to moderate inflammatory changes while that of other groups ranged from moderate to severe alterations in the mice tissue. These results showed that Mefloquine which is FDA approved, already marketed and commercially available on a global scale has an excellent anti parasitic activity against C. parvum infection with single dose application; which saves time, cost and efforts to
search for additional or alternative drugs for treating cryptosporidiosis. More large scale studies are needed to illustrate its dose response relationship using multiple doses regimens, performance and limitations on immunocompromized population, synergistic effect with already approved drugs , mechanism of action on Cryptosporidium parasite and its possible role in chemoprophylaxis specially for high risk individuals.