Cryptosporidiosis after treatment with fingolimod: a case report and pharmacovigilance review.

BACKGROUND: Cryptosporidium sp. are common intracellular parasites responsible of severe diarrhea in T-cell-immunocompromised patients. We report the first case of a woman who contracted cryptosporidiosis after treatment with fingolimod, a drug labeled for multiple sclerosis and responsible for marked lymphopenia. CASE PRESENTATION: A 60-year-old woman was admitted for abdominal pain diarrhea and fever. The patient suffered from multiple sclerosis and had been treated with fingolimod from august 2017 to september 2018 time of occurrence of the first digestive symptoms. Stool culture was negative but parasitological examination was positive for Cryptosporidium sp. Blood biological examination profound lymphopenia of 240/mm3 [17 CD4/mm3 (7%) and 32 CD8/mm3 (14%)]. Fingolimod was stopped, and the patient was put on nitazoxanide 500 mg bid for 7 days. The diarrhea resolved and no relapse was observed. Six other cases were found in the Pharmacovigilance database. CONCLUSION: Physicians should be aware of this association and screen for Cryptosporidium in cases of diarrhea in patients treated with fingolimod. Patients should be aware of this risk and advise to take appropriate measures to avoid such contamination.

Ruling out nosocomial transmission of Cryptosporidium in a renal transplantation unit: case report.

BACKGROUND: Cryptosporidium spp. is a ubiquitous parasite affecting humans as well as domestic and wild vertebrates, causing diarrhea in both immunocompetent and immunocompromised hosts worldwide. Its transmission occurs primarily by the fecal-oral route. In humans, C. parvum and C. hominis are the most prevalent species, whereas immunocompetent and immunocompromised individuals can also be infected by other zoonotic species. Renal transplant patients are prone to develop cryptosporidiosis, which can induce severe and life-threatening diarrhea. CASE PRESENTATION: We report here a series of nearly concomitant cases of acute symptomatic cryptosporidiosis in three renal transplant patients attending the Strasbourg University Hospital Nephrology Unit. The clinical presentation was persistent diarrhea and acute renal failure. The diagnosis was confirmed by microscopic stool examination using a modified Ziehl-Neelsen staining method and species identification by molecular tools. All patients were treated with nitazoxanide and recovered from diarrhea after 14 days of therapy. CONCLUSION: Genotypic species identification was not consistent with an epidemic context, thus underlining the need for genotyping to monitor at risk patients.

[Evaluation of in vitro efficacy of combined riboflavin and ultraviolet-A (365 nm) for Acanthamoeba]. / Efficacité anti-amibienne in vitro de l'association riboflavine/UV-A.

INTRODUCTION: Acanthamoeba keratitis is a rare but serious disease and is particularly difficult to treat when the diagnosis is delayed, partly because of the limitations of current therapies. The purpose of our study is to evaluate the anti-amoebic effectiveness of riboflavin and UV-A on Acanthamoeba castellani. MATERIALS AND METHODS: We tested the effect of 0.02% chlorhexidine alone (C), the combination of riboflavin 1% and UV-A (UV-A+R), and the combination of the two treatments (R+C+UV-A) on cultures of vegetative and cystic forms of A. castellani. We conducted a parasite count under optical microscopy for each treated area at day 1, 4 and 8. RESULTS: There was a decrease in the number of cysts for all three treatments (C, UV-A+R, R+C+UV-A). This reduction was greater for the plates treated with R+UV-A (P <0.01 at D8) and those treated with C+R+UV-A (P<0.001 at D8) compared to those exposed to chlorhexidine alone (C). There was no decrease in the number of amoebic trophozoites for the three treatments (C, UV-A+R, R+C+UV-A), but encystment was observed. DISCUSSION: Given the in vitro efficacy of riboflavin combined with UV-A against cystic forms of A. castellani and excellent in vivo tolerance of the procedure, the treatment of acanthamoeba keratitis might be improved by this new therapeutic approach.

[Human subcutaneous dirofilariosis due to Dirofilaria repens. A case diagnosed in Strasbourg, France]. / Dirofilariose sous-cutanée humaine due à dirofilaria repens. A propos d'un cas diagnostiqué à Strasbourg, France.

We report a case of human dirofilariosis in a 35 year-old man living in Alsace (North-East France), who presented a subcutaneous nodule of the left cheek, strongly simulating an epidermic cyst. Surgical excision and histopathological examination unexpectedly established the diagnosis by the presence of nematode worm sections identified as Dirofilaria (Nochtiella) repens. This patient living in a rural area of Strasbourg spent one week in Toulon, Southern France. This new observation of cutaneous dirofilariosis constitutes the third Alsatian case described in literature, and emphasizes the presence of this parasitic disease in Southern France.

Cellular and molecular physiopathology of congenital toxoplasmosis: the dual role of IFN-gamma.

Toxoplasma gondii is one of the few pathogens that can cross the placenta. Frequency and severity of transmission vary with gestational age. While the control of acquired toxoplasmosis is already well explored, the control of materno-foetal transmission of the parasite remains almost unknown. This is partly due to the lack of an animal model to study this process. This review summarises the studies which have been undertaken and shows that the mouse is a valuable model despite obvious differences to the human case. The paramount role of the cellular immune response has been shown by several experiments. However, IFN-gamma has a dual role in this process. While its beneficial effects in the control of toxoplasmosis are well known, it also seems to have transmission-enhancing effects and can also directly harm the developing foetus. The ultimate goal of these studies is to develop a vaccine which protects both mother and foetus. Therefore, it is useful to study the mechanisms of natural resistance against transmission during a secondary infection. In this setting, the process is more complicated, involving both cellular and also humoral components of the immune system. In summary, even if the whole process is far from being elucidated, important insights have been gained so far which will help us to undertake rational vaccine research.

Role of gamma interferon and T cells in congenital Toxoplasma transmission.

In the BALB/c mouse model, primary infection with Toxoplasma gondii during the second third of gestation leads to a high percentage of infected foetuses. However, immunity induced by infection contracted before pregnancy prevents parasites from crossing the placenta and completely protects the foetuses, as well as the pregnant women. In order to clarify the roles of CD4+, CD8+ T lymphocytes and IFN-gamma in this protection, pregnant BALB/c mice were treated with depleting monoclonal antibodies against CD4, CD8, IFN-gamma, or control antibody. Only the foetuses of the groups treated with anti-CD8 and anti-IFN-gamma antibodies developed congenital toxoplasmosis. The maternal production of IFN-gamma was depressed in the mice depleted of CD4 and CD8 cells (P < 0.001). Determination of the blood parasite load demonstrated that materno-foetal transmission of T. gondii correlates with maternal parasitaemia. Together, these results show that CD8+ T lymphocytes and IFN-gamma play an important role in protection against congenital toxoplasmosis during reinfection.

Prospective assessment of a new polymerase chain reaction target (STEVOR) for imported Plasmodium falciparum malaria.

The diagnostic value of a polymerase chain reaction (PCR)-based method for amplifying a new target of repeated genes (STEVOR) in Plasmodium falciparum was prospectively assessed on samples from 210 febrile patients returning from areas endemic for malaria. This method is capable of detecting 0.01 parasites in one microliter of blood. Plasmodium falciparum STEVOR PCR confirmed the results of the thin- and thick-film direct examination method but identified Plasmodium falciparum in four patients in whom direct examination was inconclusive at the species level. Moreover, PCR was positive in two patients with a negative direct examination. Thus, Plasmodium falciparum STEVOR PCR had 100% sensitivity and specificity and could be used in selected parasitology laboratories when expert advice is required.