Travelers with cutaneous leishmaniasis cured without systemic therapy.

BACKGROUND: Cutaneous leishmaniasis (CL) is a disfiguring but not life-threatening disease. Because antileishmanial drugs are potentially toxic, the World Health Organization (WHO) recommends simple wound care or local therapy as first-line treatment, followed or replaced by systemic therapy if local therapy fails or cannot be performed. METHODS: To determine the feasibility and impact of the recommended approach, we analyzed the results of a centralized referral treatment program in 135 patients with parasitologically proven CL. RESULTS: Infections involved 10 Leishmania species and were contracted in 29 different countries. Eighty-four of 135 patients (62%) were initially treated without systemic therapy. Of 109 patients with evaluable charts, 23 of 25 (92%) treated with simple wound care and 37 of 47 (79%) treated with local antileishmanial therapy were cured by days 42-60. In 37 patients with large or complex lesions, or preexisting morbidities, or who had not been cured with local therapy, the cure rate with systemic antileishmanial agents was 60%. Systemic adverse events were observed in 15 patients, all receiving systemic therapy. CONCLUSIONS: In this population of CL patients displaying variable degrees of complexity and severity, almost two-thirds of patients could be initially managed without systemic therapy. Of these, 60 were cured before day 60. The WHO-recommended stepwise approach favoring initial local therapy therefore resulted in at least 44% of all patients being cured without exposure to the risk of systemic adverse events. Efforts are needed to further simplify local therapy of CL and to improve the management of patients with complex lesions and/or preexisting comorbidities.

A global analysis of mucormycosis in France: the RetroZygo Study (2005-2007).

BACKGROUND: Mucormycosis is a deadly invasive fungal infection whose characteristics are only partially understood. METHODS: Data on mucormycosis obtained in France between 2005 and 2007 from 2 notification systems were merged. The 2008 European Organisation for Research and Treatment of Cancer/Mycoses Study Group definition criteria were applied and risk factors for death were analyzed by hazard ratios (HRs) calculated from the Cox proportional hazards regression model. RESULTS: A total of 101 cases (60 proven, 41 probable), mostly in men (58%) >50 years (mean age, 50.7 ± 19.9) were recorded. Hematological malignancies represented 50% (median time for occurrence, 8.8 months after disease onset), diabetes 23%, and trauma 18% of cases. Sites of infection were lungs (28%; 79% in hematology patients), rhinocerebral (25%; 64% in diabetic patients), skin (20%), and disseminated (18%). Median time between first symptoms and diagnosis was 2 weeks. The main fungal species were Rhizopus oryzae (32%) and Lichtheimia species (29%). In cases where the causative species was identified, R. oryzae was present in 85% of rhinocerebral forms compared with only 17% of nonrhinocerebral forms (P < .001). Treatment consisted of surgery in 59% and antifungals in 87% of cases (liposomal amphotericin B in 61%). Ninety-day survival was 56%; it was reduced in cases of dissemination compared with rhinocerebral (HR, 5.38 [2.0-14.1]; P < .001), pulmonary (HR, 2.2 [1.0-4.7]; P = .04), or skin localization (HR, 5.73 [1.9-17.5]; P = .002); survival was reduced in cases of hematological malignancies compared with diabetes mellitus (HR, 2.3 [1.0-5.2]; P < .05) or trauma (HR, 6.9 [1.6-28.6], P = .008) and if ≥2 underlying conditions (HR, 5.9 [1.8-19.0]; P = .004). Mucormycosis localization remained the only independent factor associated with survival. CONCLUSIONS: This 3-year study performed in one country shows the diverse clinical presentation of mucormycosis with a high prevalence of primary skin infection following trauma and a prognosis significantly influenced by localization.

Estimating the burden of mucormycosis infections in France (2005-2007) through a capture-recapture method on laboratory and administrative data.

BACKGROUND: Mucormycoses are rare but severe fungal infections whose incidence is increasing, particularly in immunosuppressed and diabetic patients. Following a retrospective study on the characteristics and outcomes of cases who were identified through two sources of information, we carried out a capture-recapture method to estimate the actual burden of the disease in France, 2005-2007. METHODS: An administrative dataset from the national hospital discharge system and a laboratory dataset from the National Reference Centre for Mycoses and Antifungals were combined to identify patients from 2005 to 2007. We applied capture-recapture equations to estimate the number of cases missed by both sources and to assess the advantages of each dataset, especially in terms of sensitivity. RESULTS: There were 94 mucormycosis cases included in the study: 30 and 31 in each respective source and 33 common to both. Capture-recapture showed that 28 cases were missed (expected total: 122 cases, CI95: 102-142). Each dataset had a sensitivity value below 53%. The merged set yielded a 77% sensitivity (66%-92%). CONCLUSION: This study highlights the importance of combining available sources when analysing rare infectious diseases. The proportion of 23% missed cases might seem acceptable given the scarcity of the disease, for which further knowledge is needed. However this proportion could decrease in the future, through the sensitization of clinicians, pathologists and mycologists together with the improving quality of discharge datasets.

[Cutaneous leishmaniasis in France: towards the end of injectable therapy?]. / La leishmaniose cutanée en France: vers la fin des traitements injectables?

Today no drug likely to be efficient on the majority of human-infecting species, well tolerated, and easy to administer is available for the treatment of human cutaneous leishmaniasis. But recent progress has been made. Efficient against visceral leishmaniasis, orally administered miltefosine may supplant pentavalent antimonials for the treatment of cutaneous leishmaniasis acquired in the New World. Right now, the reference treatment is still parenteral pentavalent antimonials 20 mg Sbv/kg/d for a duration that may probably be reduced from 20 to 10 days. The benefit/risk ratio of pentamidine still compares well with that of pentavalent antimonials for the treatment of lesions due to species belonging to the L. panamensis/L. guyanensis/L. shawi group. Pentamidine, which is easier to handle than antimonials, remains the reference treatment for cases from areas where these species predominate. Oral fluconazole is an improvement, readily available for cases from L. major foci. If its efficacy is confirmed in other foci and against other species, mechanisms will have to be implemented to make this therapeutic improvement affordable to poor patients in endemic countries. The development of an efficient and well tolerated topical treatment is still warranted. A new formulation of aminosidine is currently under evaluation. One can hope that the treatment of cutaneous leishmaniasis will soon become simpler, both for patients and doctors. For the benefits of this simplification to be rapidly affordable to all patients, the pharmaceutical and clinical research outlay must be maintained.

Local control of rhino-orbito-cerebral mucormycosis dramatically impacts survival.

Surgery and antifungals are the reference standard for rhino-orbito-cerebral mucormycosis (ROCM) treatment. The impact of local control on survival of 22 consecutive ROCM adults was studied on day 90: none vs. 75% died, respectively, with or without local control (p <0.0001). Hence, repeated surgical procedures are recommended to achieve local control of ROCM.