Sclerosing cholangitis presents with right upper quadrant pain, vomiting and raised alkaline phosphatase levels. 4.4.3.3 Diagnosis. The diagnosis of cryptosporidiosis is made by a stool flotation method with subsequent Ziehl–Neelsen, auramine phenol or acid-fast trichrome staining to differentiate oocysts from yeasts [71]. Oocysts may be detected more easily by direct

immunofluorescence or enzyme-linked immunosorbent assay [72], which have a similar sensitivity to PCR techniques [73]. In individuals with profuse diarrhoea, cryptosporidiosis may be detected in a single stool sample, but multiple samples may be required in those with less severe infection HSP inhibitor review as oocyst excretion may be intermittent. Small bowel and rectal histology may be useful although the latter has a low sensitivity for diagnosis. In individuals with abdominal pain, endoscopic retrograde cholangio-pancreatography (ERCP) may reveal ampullary stenosis and sclerosing cholangitis with associated thickening of the gall bladder wall. 4.4.3.4 Treatment. There is no Ruxolitinib supplier specific treatment targeting cryptosporidium directly. Early HAART is imperative and is associated with complete resolution of infection following restoration of immune function [74,75]. In individuals with profuse diarrhoea, therapeutic drug monitoring may be required to confirm adequate absorption of antiretroviral

agents. Paromomycin is active in animal models [76], although a recent meta-analysis has shown no evidence for clinical effectiveness [77]. A study combining paromomycin with azithromycin reported substantial reduction in stool frequency and volume, together with diminished oocyst shedding [78].

Paromomycin was given orally as 500 mg four times daily or 1 g twice daily for up to 12 weeks. The dose of azithryomycin was 500 mg daily. However the small numbers in this study and the limited experience of this combination preclude its choice as a front line therapy. Nitazoxanide has been approved for use in immunocompetent individuals but has not been shown to be superior to placebo in the severely immunocompromised [79]. If used, nitazoxanide is given at a dose of 500 mg twice daily for 3 days, but may be required for up to 12 weeks. Trials have also investigated a larger dose of 1 g bd po [80]. When an anti-cryptosporidial agent is chosen nitazoxanide check details is the preferred agent but its efficacy is limited in more immunocompromised patients. Supportive therapy with iv fluid replacement/antimotility agents is essential. First-line treatment for cryptosporidiosis is with effective antiretroviral therapy (category recommendation III). 4.4.3.5 Impact of HAART. The use of optimized HAART should be continued to prevent relapse 4.4.3.6 Prevention. Standard drinking water chlorination techniques are not sufficient to eradicate the parasite. Specific filtration employing an ‘absolute’ 1-micron filter is required [81].