Approach

Disease is self-limiting in immunocompetent patients. No treatment is normally required, other than measures to prevent dehydration, such as oral rehydration solution. Treatment modalities are limited. Nitazoxanide is the only drug approved by the US Food and Drug Administration (FDA) to specifically treat cryptosporidiosis and can be prescribed for use in immunocompetent patients aged ≥1 year.[69]​ However, specific treatment is not normally required because the disease is self-limiting in this patient group. In immunocompromised patients with severe or refractory disease, the benefit of nitazoxanide is unproven although the drug may be prescribed.[85]

Asymptomatic carriage occurs in both immunocompetent and immunocompromised patients; however, treatment is not required in these patients.

Immunocompetent patients

Disease is self-limiting in immunocompetent patients. Symptoms usually resolve in 7 to 14 days, although they may last for 3 to 4 weeks (in patients who seek medical attention the mean is 13 days, median 11 days).[38] Improvement is followed by brief recurrence of symptoms in about one third of cases.[38][73] No treatment is normally required, other than measures to prevent dehydration, such as oral rehydration solution.

If treatment is required, such as when symptoms persist, nitazoxanide can be prescribed for immunocompetent patients aged ≥1 year and is well tolerated.[69]​ Even with treatment, however, it takes up to 5 days for diarrhoea to resolve in 80% of cases.[86] Where there is little improvement, patients have been treated with multiple 3-day courses of nitazoxanide, and 7-day courses have also been used.[87][88][89]

There are no definitive criteria for when treatment should be instituted, and treatment is not mandatory even if diarrhoea lasts for >7 days; however, some physicians may choose to treat the infection as soon as it is diagnosed.

Immunocompromised patients

Disease may be prolonged and refractory to treatment in immunocompromised patients. Antimicrobial therapy may ameliorate symptoms but is seldom curative, with relapse often occurring when treatment is discontinued. Other concurrent opportunistic infections should be ruled out. In general, the principle for treatment in immunocompromised patients is to address the underlying immune deficiency, which in turn will result in improvement of cryptosporidiosis.

In patients with HIV infection, antiretroviral therapy is the treatment of choice.[90][91]​​ As well as improving the level of CD4 cells and restoring a degree of immunity, protease inhibitors reduce host-cell invasion by Cryptosporidium sporozoites and parasite development in vitro.[92] In other types of immune deficiency, improving immunity by treating the primary disorder where possible can also lead to improvement.[93] Patients at high risk for severe cryptosporidiosis include those with leukemia and lymphoma (particularly children), or those with primary T-cell immune deficiency. In severe cases of cryptosporidiosis, supportive treatment may be required; this may include intravenous rehydration, and correction of electrolytes if much fluid loss has occurred.

Nitazoxanide is not approved to treat immunocompromised patients, as it has not been shown to be superior to placebo in these patients. In the face of disease in an immunocompromised patient, which may be fatal if refractory and/or severe, clinicians may nonetheless elect to use nitazoxanide. In patients with HIV infection, nitazoxanide (14-day course) may be used in conjunction with antiretroviral therapy.​[90]​[91]​​[94]

Other agents

Other agents have been used for the treatment of cryptosporidiosis, but the evidence for their efficacy is weak, and they are not licensed for this indication.[85]​[90]​​

Paromomycin

  • The aminoglycoside paromomycin is poorly absorbed from the GI tract and has been used as an oral agent for cryptosporidiosis, showing some benefit in patients with HIV/AIDS.[95][96][97]

Azithromycin

  • There are anecdotal reports of responses to azithromycin,​​​ but others have found no benefit.[98]​[99]​[100]​[101]

  • The use of azithromycin in combination with paromomycin has been documented to be successful in case reports and in an uncontrolled series of patients with AIDS.[102][103]​ Therefore, some clinicians experienced in the management of immunocompromised patients with severe or life-threatening cryptosporidiosis advocate the combination of nitazoxanide, paromomycin, and azithromycin.

Decreasing immunosuppression in people receiving immunosuppressive drugs and use of nitazoxanide (alone or in combination with other agents) may provide improvement or resolution of symptoms.[104]​

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