Cryptosporidial diarrhoea in two HIV-infected patients: potential efficacy of rifampicin for successful treatment

Abstract

Cryptosporidium parvum is a protozoa responsible for severe chronic diarrhoea in HIV-infected patients, especially when the CD4 cell count is below 200 cells/μl [1]. The lack of effective treatment and the propensity of the parasite to survive in and be transmitted through source waters make it an important public health threat, particularly in HIV-infected patients and in developing countries where C. parvum is associated with 24% of diarrhoea in such patients [2]. To date, immune reconstitution is the best available treatment for cryptosporidiosis. Paramomycin and azithromycin are poorly effective. Nitazoxanide has showed some efficacy but diarrhoea often relapses and it is not easily available. Rifamycins could be a possible alternative. Rifabutin, in association with azithromycin, has been shown to prevent cryptosporidiosis in advanced HIV infection [3], and rifaximin, a non-absorbable rifamycin drug, has eradicated C. parvum in five patients with CD4 cell counts below 200 cells/μl, with no relapse after 1–7 months of follow-up [4]. Here we describe two HIV-infected patients, in whom cryptosporidiosis was cured by rifampicin. Case 1 A 51-year-old man from Cameroon was admitted for loose diarrhoea (five to 10 episodes per day) and weight loss. Physical examination revealed oral candidiasis and inguinal lymph nodes. A diagnosis of HIV infection was confirmed by serology. The initial CD4 cell count was 13 cells/μl and the HIV viral load was 507 000 copies/ml. Stool tests and culture identified C. parvum oocysts. Meanwhile, histological examination of the inguinal lymph node showed acid fast bacilli favouring the diagnosis of tuberculosis. Treatment with isoniazid, rifampicin (10 mg/kg a day), ethambutol and pyrazinamid was initiated. Acute hepatitis occurred on day 6 and was attributed to pyrazinamide, which was changed for moxifloxacin. No other specific drug against Cryptosporidium spp. was added. Two weeks after the treatment was started the diarrhoea had stopped. The parasitological follow-up showed a progressive decrease in the number of cryptosporidial oocysts. On day 2, optical microscopy and polymerase chain reaction were positive and optical microscopy was coded +++; on day 20, optical microscopy and polymerase chain reaction were still positive but optical microscopy was coded +; at day 60, both tests were negative. HAART was instituted 4 months after the beginning of antituberculosis therapy. After 10 months of follow-up, although antituberculous therapy had been interrupted and the CD4 cell count remained below 100 cells/μl despite HAART, the patient did not relapse. Case 2 A 61-year-old man from Algeria was admitted for watery diarrhoea (> 15 episodes per day) responsible for severe dehydration. He has been HIV infected for 3 years and was receiving HAART (lamivudine, didanosine, fosamprenavir, ritonavir) and atovaquone since diagnosis, but compliance was poor. His CD4 cell count was 28 cells/μl and the HIV viral load was 25 100 copies/ml. Stool tests and culture identified C. parvum oocysts coded +++ on optical microscopy. After 2 weeks of nitazoxanide, the diarrhoea persisted and stools were still +++ positive for Cryptosporidium oocysts. Given its spectacular efficacy in the previous patient, rifampicin (20 mg/kg a day) was thus added via intravenous infusion to by-pass malabsorption related to diarrhoea. The outcome was complicated by severe sepsis presumed to be caused by methicillin-resistant Staphylococcus aureus, initially treated with vancomycin. After blood cultures identified Escherichia coli, vancomycin was switched for cefotaxim and amikacin, whereas rifampicin was maintained. After 13 days of rifampicin and 28 days of nitazoxanide, the diarrhoea had stopped and stool tests were negative for Cryptosporidium and remained so until the patient died of Serratia marcescens endocarditis 1.5 months later. These two cases suggest that rifampicin may be effective in the treatment of cryptosporidial diarrhoea in HIV-infected patients. Although there is no report of such an efficacy, this is not surprising given the presumed efficacy on cryptosporidiosis of rifabutin in association with azithromycin [3] and rifaximin [4], two drugs also belonging to the family of rifamycins. This has multiple consequences: the administration of rifamycins should systematically be evaluated as a counfounding factor in any trial evaluating the efficiency of any drug in the therapy of cryptosporidiosis, and the use of rifamycins should be discussed in cases of resistant cryptosporidiosis. Finally, a clinical trial evaluating the efficacy of rifamycin drugs in the treatment of cryptosporidiosis is warranted. Nevertheless, the choice of a drug belonging to the rifamycin family remains a cause of concern and rifampicin may not be the preferred drug in this setting. Rifampicin is an enzymatic inducer with multiple drug interactions, and is also an antibacterial agent that carries the risk of the emergence of resistance in the case of ongoing tuberculosis or staphylococcal infection. Therefore, it would probably be better to use a non-absorbable rifamycin drug such as rifaximin, but this drug is not available everywhere. The first two authors equally contributed to this work.