Case Report: Intravenous Pentamidine Rescue Treatment for Active Chronic Visceral Leishmaniasis in an HIV-1 Infected Patient.

The management of visceral leishmaniasis (VL) in HIV-infected patients is complex because of high mortality rates, toxic drug-related side effects, and a high risk of treatment failure and relapse. We report a case of active chronic VL in an HIV-1-infected woman presenting multiple secondary VL episodes over 7 years leading to massive splenomegaly and blood transfusion-dependent anemia despite several treatment courses and secondary prophylaxis. The patient was finally successfully treated with rescue treatment based on intravenous pentamidine. Twenty months after discontinuation of pentamidine the patient presented complete clinical and parasitological response. In patients with active chronic VL, treatment with intravenous pentamidine can be effective and should be considered as rescue treatment.

Refractory mucocutaneous leishmaniasis resolved with combination treatment based on intravenous pentamidine, oral azole, aerosolized liposomal amphotericin B, and intralesional meglumine antimoniate.

INTRODUCTION: Mucocutaneous leishmaniasis (MCL) is a complication of tegumentary leishmaniasis, causing potentially life-threatening lesions in the ear, nose, and throat (ENT) region, and most commonly due to Leishmania (Viannia) braziliensis. We report a case of relapsing MCL in an Italian traveler returning from Argentina. CASE DESCRIPTION: A 65-year-old Italian male patient with chronic kidney disease, arterial hypertension, prostatic hypertrophy, and type-2 diabetes mellitus was referred for severe relapsing MCL acquired in Argentina. ENT examination showed severe diffuse pharyngolaryngeal edema and erythema, partially obstructing the airways. A nasopharyngeal biopsy revealed a lymphoplasmacytic inflammation and presence of Leishmania amastigotes, subsequently identified as L. (V.) braziliensis by hsp70 PCR-RFLP analysis and sequencing. Despite receiving four courses of liposomal amphotericine B (L-AmB) and two courses of miltefosine over a 2-year period, the patient presented recurrence of symptoms a few months after the end of each course. After the patient was referred to us, a combined treatment was started with intravenous pentamidine 4 mg/kg on alternate days for 10 doses, followed by one dose per week for an additional seven doses, intralesional meglumine antimoniate on the nasal lesion once per week for six doses, oral azoles for three months, and aerosolized L-AmB on alternate days for three months. The treatment led to regression of mucosal lesions and respiratory symptoms. Renal function temporarily worsened, and the addition of insulin was required to maintain glycemic compensation after pentamidine discontinuation. CONCLUSIONS: This case highlights the difficulties in managing a life-threatening refractory case of MCL in an Italian traveler with multiple comorbidities. Even though parenteral antimonial derivatives are traditionally considered the treatment of choice for MCL, they are relatively contraindicated in cases of chronic kidney disease.The required dose adjustment in cases of impaired renal function is unknown, therefore the use of alternative drugs is recommended. This case was resolved with combination treatment, including aerosolized L-AmB, which had never been used before for MCL.

Clofazimine: an old drug for never-ending diseases.

Clofazimine (CFZ), an old hydrophobic riminophenazine, has a wide range of antimycobacterial activity ranging from leprosy to nontuberculous mycobacterial diseases. CFZ has several advantages such as a favorable pharmacokinetic profile, dose-dependent side effects as well as low price. In this narrative review, we have assessed the clinical development of CFZ, starting from the potential in vitro mechanism of actions, to the spectrum of side effects and potential drug-drug interactions, highlighting its current place in therapy and future possible use in leprosy, nontuberculous mycobacterial diseases and drug-resistant tuberculosis.

Delay in schistosomiasis diagnosis and treatment: a multicenter cohort study in Italy.

BACKGROUND: Barriers to access to care, different diagnostic strategies and low awareness remain challenging issues in the fight against schistosomiasis.Our study aims to examine management of schistosomiasis in migrants attending large tertiary hospitals in Italy, in order to call for a comprehensive approach. METHODS: A retrospective review of schistosomiasis cases was carried out between January 1, 2016, and December 31, 2017, in five large Infectious Disease Centers in Italy. We included all patients diagnosed with schistosomiasis. We differentiated among (i) asymptomatic patients diagnosed by serology either as healthy 'migrant evaluation' or as 'late evaluation' in patients followed because of a different infection and (ii) patients tested because of a suggestive clinical presentation. Patients characteristics and clinical data were recorded. RESULTS: One hundred forty-nine patients were included, 137 (91.9%) were male, the median age was 26 years and 70% of them came from Sub-Saharan Africa.Thirty-eight asymptomatic patients (25.5%) were diagnosed by serology [15, (10.1%) among 'migrant evaluation' and 23 (15.4%) among 'late evaluation' group], and 111 (74.5%) presented with signs/symptoms.The median diagnostic delay from arrival in Italy was 31 months: 110 for asymptomatic group and 16 months for symptomatic patients. Among the 111 symptomatic patients, 41 individuals were already followed in our clinics, and they never underwent screening before appearance of evident disease. Among patients with positive serology who were tested by microscopy, 32/86 (37.2%) had confirmed diagnosis. Forty-five (37.8%) patients presented radiologic abnormalities. Praziquantel was the treatment of choice (70.1% for 3 days and 29.9% in a single-day dose), and 77 (51.7%) were lost to follow-up. CONCLUSIONS: In our centers, a high proportion of patients were tested late after arrival, and most of them presented with clinical apparent disease. Well-defined strategies and implementation of recent guidelines are needed to improve early diagnosis and to overcome heterogeneity of practice.

Schistosomiasis, strongyloidiasis and Chagas disease: the leading imported neglected tropical diseases in Italy.

BACKGROUND: In recent years, an increasing number of individuals affected by neglected tropical diseases (NTDs) have been observed in Italy, due to migration, international travels and climate changes. Reliable data on the current NTD epidemiology in Italy and the health system preparedness on this issue are not available. METHODS: We report the results of a survey on selected NTDs (schistosomiasis, strongyloidiasis, echinococcosis, Chagas disease, leishmaniasis, cysticercosis, filariasis and scabies) in nine Italian sentinel centres, in order to investigate their occurrence throughout the country and identify which ones are a priority for public health interventions, development of protocols for case management, and training activities. To explore the preparedness of the centres, we investigate the availability of specific diagnostic tools and drugs, needed for the management of the most common NTDs. We also reviewed and summarized the available national policies, recommendations and guidelines on NTDs in Italy. RESULTS: Overall, 4123 NTDs cases were diagnosed in nine Italian centres within a 7-year period (2011-2017). Schistosomiasis and strongyloidiasis were the most common NTDs, accounting for about one-third each of all the diagnosed cases, followed by Chagas disease. The number of cases showed a significant trend to increase over time, mainly due to foreign-born subjects. Serology for Schistosoma spp. and Strongyloides stercoralis was available in seven and five centres, respectively. Agar plate stool culture for S. stercoralis was available in three sites. Ivermectin and praziquantel were always available in six centres. Six national policies, recommendations and guidelines documents were available, but for the most part, they are not fully implemented yet. CONCLUSIONS: This survey showed how some NTDs, such as schistosomiasis and strongyloidiasis, are becoming more common in Italy, due to multiple components. A list of seven key actions was proposed, in order to improve diagnosis, management and control of NTDs in Italy.

The use of circulating cathodic antigen rapid test and serology for diagnosis of active Schistosoma mansoni infection in migrants in Italy, a non-endemic country: a cross sectional study.

Diagnosis of schistosomiasis in migrants coming from endemic areas can be difficult, especially in asymptomatic subjects. Light-intensity disease, in fact, may be missed due to the low sensitivity of the stool microscopy and serologic testing cannot distinguish between a resolved infection and an active infection in patients who have been infected and treated in the past, because specific antibodies can persist despite cure. We describe a cross-sectional study conducted on 82 migrants tested for Schistosoma mansoni on single blood (anti-schistosome antibodies, total IgE) and urine [point-of-care (POC) circulating-cathodic-antigen (CCA) test] samples. A positive POC-CCA test (active infection) resulted in two untreated patients with a positive serology while all patients (n = 66) with a past infection showed a negative POC-CCA test. POC-CCA urine test in combination with serology may be helpful in rapidly differentiate active from past S. mansoni infection in migrants coming from endemic areas.

The use of circulating cathodic antigen rapid test and serology for diagnosis of active Schistosoma mansoni infection in migrants in Italy, a non-endemic country: a cross sectional study

ABSTRACT Diagnosis of schistosomiasis in migrants coming from endemic areas can be difficult, especially in asymptomatic subjects. Light-intensity disease, in fact, may be missed due to the low sensitivity of the stool microscopy and serologic testing cannot distinguish between a resolved infection and an active infection in patients who have been infected and treated in the past, because specific antibodies can persist despite cure. We describe a cross-sectional study conducted on 82 migrants tested for Schistosoma mansoni on single blood (anti-schistosome antibodies, total IgE) and urine [point-of-care (POC) circulating-cathodic-antigen (CCA) test] samples. A positive POC-CCA test (active infection) resulted in two untreated patients with a positive serology while all patients (n = 66) with a past infection showed a negative POC-CCA test. POC-CCA urine test in combination with serology may be helpful in rapidly differentiate active from past S. mansoni infection in migrants coming from endemic areas.

Imported rickettsioses in Italy.

BACKGROUND: In Italy few cases of rickettsioses have been reported in travellers and autochthonous cases are attributed predominantly to Rickettsia conorii, the agent of Mediterranean spotted fever. METHOD: The purpose of this study was to investigate some epidemiological and clinical features of tick-borne spotted fever group rickettsiosis acquired abroad or in Italy. Serum specimens collected prospectively from patients with suspected rickettsioses were tested by immunofluorescence assay. A definitive diagnosis was made on the basis of positive serological test results at the WHO collaborative centre for rickettsial diseases, Marseille, France. We compared the clinical features of patients with confirmed rickettsioses and those showing typical clinical symptoms/signs without definitive diagnose. RESULTS: Eight of 26 patients suspected cases had confirmed rickettsioses. All patients were travellers returning from southern Africa (75% Rickettsia africae). Inoculation eschars were significantly more common in patients with confirmed rickettsioses (p = 0.004). CONCLUSIONS: Our study demonstrates that R. africae is the most frequent rickettsia observed in Italian travellers. Prior to receiving the laboratory results, physicians should start empirical treatment on the basis of epidemiologic data (e.g., travel history to Africa), and clinical findings compatible with rickettsioses (e.g., eschars).

Post-Kala-Azar dermal leishmaniasis in an HIV-1-infected woman: recovery after amphotericin B following failure of oral miltefosine.

We describe a case of post-kala-azar dermal leishmaniasis occurring after diagnosis of visceral leishmaniasis in an HIV-1-infected woman. The skin lesions did not recover after treatment with oral miltefosine at 100 mg/day for five cycles of 28 days but responded to treatment with liposomal amphotericin B.

Leishmania infection can hamper immune recovery in virologically suppressed HIV-infected patients.

An HIV-infected patient started combination antiretroviral therapy with 13 CD4+ cells/microL. Despite sustained virological suppression over the following four years, the anemia did not resolve, and the CD4+ cell counts always remained below 200/microL until co-infection with Leishmania was diagnosed in October 2006 when the patient started complaining of persistent mild fever and asthenia. Once treatment for leishmaniasis was started with miltefosine, CD4+ cell count rose above 400/microL. A new drop in CD4+ cell count was observed when Leishmania DNA turned out again to be positive, but treatment with liposomal amphotericin-B restored immune recovery.

Respiratory syndrome and respiratory tract infections in foreign-born and national travelers hospitalized with fever in Italy.

BACKGROUND: We measured frequency and epidemiologic, clinical, and hematochemical variables associated with respiratory tract infections (RTIs) in foreign-born and national patients hospitalized with fever with a history of international travel, and compared the final diagnosis of RTI with the presence of a respiratory syndrome (RS) at presentation. METHODS: A prospective, multicenter, observational study was conducted at tertiary care hospitals in Northern Italy from September 1998 to December 2000. RESULTS: A final diagnosis of RTI was obtained in 40 cases (7.8%), 27 (67.5%) with lower RTI and 13 (32.5%) with upper RTI. The most common RTIs were pneumonia (35%) and pulmonary tuberculosis (15%). A white blood cell count > or = 10,000 and an erythrocyte sedimentation rate > or = 20 mm/h were independently associated with a final diagnosis of RTI; onset of symptoms at > or = 16 days and > or = 75% neutrophils were independently associated with lower RTI. An RS was identified in 51 (9.9%) of 515 travelers. Sensitivity, specificity, and positive and negative predictive values of a diagnosis of RS for a final diagnosis of RTI were 67.5%, 94.9%, 52.9%, and 97.2%, respectively. CONCLUSIONS: Pneumonia and pulmonary tuberculosis were frequent among foreign-born and national travelers with fever admitted to a tertiary care hospital. Half of the pneumonia cases did not present with an RS at first clinical examination.

Mefloquine versus quinine plus sulphalene-pyrimethamine (metakelfin) for treatment of uncomplicated imported falciparum malaria acquired in Africa.

We conducted a multicenter, randomized, open-label trial to compare mefloquine with a 3-day quinine plus sulphalene-pyrimethamine (SP) regimen for the treatment of imported uncomplicated malaria acquired in Africa. The end points of the study were efficacy, tolerability, and length of hospital stay. From July 1999 to February 2003, 187 patients were enrolled in five centers in Italy, of whom 93 were randomized to receive mefloquine (the M group) and 94 were randomized to receive quinine plus SP (the QSP group). Immigrants and visiting relatives and friends represented 90% of the cases and were mainly from western African countries. A slightly increased proportion of cases in the QSP group had abnormal alanine aminotransferase levels at the baseline. The early cure rate was similar in the two groups: 98.9% (confidence interval [CI] = 97 to 100%) in the M group and 96.8% (CI = 93 to 100%) in the QSP group. The extended follow-up was completed by 135 subjects (72.2%), and no case of recrudescence was detected. There were no differences in the parasite clearance time, but patients in the M group had shorter mean fever clearance time (35.9 h versus 44.4 h for the QSP group; P = 0.05) and a shorter mean hospital stay (3.9 days versus 4.6 days for the QSP group; P = 0.007). The overall proportions of reported side effects were similar in the two groups, but patients in the M group had a significantly higher rate of central nervous system disturbances (29.0% versus 9.6% for the QSP group; P < 0.001).

Real-time PCR assay for clinical management of human immunodeficiency virus-infected patients with visceral leishmaniasis.

To evaluate the usefulness of a real-time PCR for Leishmania DNA in the diagnosis and follow-up of patients with human immunodeficiency virus type 1 (HIV-1) and Leishmania coinfection, Leishmania DNA levels were measured in whole peripheral blood from 25 HIV-infected patients with clinical features suggestive of visceral leishmaniasis. Leishmania DNA was detected in 10 of 25 patients with microscopically confirmed visceral leishmaniasis and in none of those without this disease. Following treatment with liposomal amphotericin B, a clinical response was observed in 9 of 10 patients, in association with significantly decreased parasite loads. Seven patients relapsed clinically a median of 110 days after the end of treatment, in association with substantial increases in Leishmania DNA levels. Leishmania DNA levels correlated with the clinical course of visceral leishmaniasis, and their measurement at diagnosis and during and after treatment seems to be useful in the clinical management of HIV-infected patients with this disease.

Malaria clusters among illegal Chinese immigrants to Europe through Africa.

Between November 2002 and March 2003, 17 cases of malaria (1 fatal) were observed in illegal Chinese immigrants who traveled to Italy through Africa. A further cluster of 12 was reported in August, 2002. Several immigrants traveled by air, making the risk of introducing sudden acute respiratory syndrome a possibility should such illegal immigrations continue.