Begoña Monge-Maillo

Imported infectious diseases in mobile populations, Spain.

Health screening of immigrant populations is needed to ensure early diagnosis and treatment.

Therapeutic options for visceral leishmaniasis.

Visceral leishmaniasis (VL), also known as Kala-Azar, is a disseminated protozoal infection caused principally by Leishmania donovani and Leishmania infantum (known as Leishmania chagasi in South America). The therapeutic options for VL are diverse and depend on different factors, such as the geographical area of the infection, development of resistance to habitual treatments, HIV co-infection, malnourishment and other concomitant infections. This article provides an exhaustive review of the literature regarding studies published on the treatment of VL, and gives therapeutic recommendations stratified according to their level of evidence, the species of Leishmania implicated and the geographical location of the infection.

Neglected tropical diseases outside the tropics.

Background The neglected tropical diseases (NTDs) cause significant morbidity and mortality worldwide. Due to the growth in international travel and immigration, NTDs may be diagnosed in countries of the western world, but there has been no specific focus in the literature on imported NTDs. Methods Retrospective study of a cohort of immigrants and travelers diagnosed with one of the 13 core NTDs at a Tropical Medicine Referral Unit in Spain during the period April 1989-December 2007. Area of origin or travel was recorded and analyzed. Results There were 6168 patients (2634 immigrants, 3277 travelers and 257 VFR travelers) in the cohort. NTDs occurred more frequently in immigrants, followed by VFR travelers and then by other travelers (p<0.001 for trend). The main NTDs diagnosed in immigrants were onchocerciasis (n = 240, 9.1%) acquired mainly in sub-Saharan Africa, Chagas disease (n = 95, 3.6%) in immigrants from South America, and ascariasis (n = 86, 3.3%) found mainly in immigrants from sub-Saharan Africa. Most frequent NTDs in travelers were: schistosomiasis (n = 43, 1.3%), onchocerciasis (n = 17, 0.5%) and ascariasis (n = 16, 0.5%), and all were mainly acquired in sub-Saharan Africa. The main NTDs diagnosed in VFR travelers were onchocerciasis (n = 14, 5.4%), and schistosomiasis (n = 2, 0.8%). Conclusions The concept of imported NTDs is emerging as these infections acquire a more public profile. Specific issues such as the possibility of non-vectorial transmission outside endemic areas and how some eradication programmes in endemic countries may have an impact even in non-tropical western countries are addressed. Recognising NTDs even outside tropical settings would allow specific prevention and control measures to be implemented and may create unique opportunities for research in future.

Old and new challenges in Chagas disease

Chagas disease, caused by the parasite Trypanosoma cruzi, is a neglected disease, which can lead to cardiomyopathy, arrhythmias, megaviscera, and more rarely, polyneuropathy in up to 30-40% of patients around 20 to 30 years after acute infection. Although it is endemic in the Americas, global population movements mean that it can be located wherever migrants from endemic areas settle. The disease was first described 100 years ago and still challenges clinicians worldwide, since diagnostic, therapeutic, and prognostic methods remain insufficient. Furthermore, factors such as HIV co-infection, immunosuppressive drugs, transplantation, and neoplastic disease can alter the natural course of the infection. We present the case of a Bolivian woman with chronic T cruzi infection diagnosed at our clinic in Madrid, Spain, who subsequently developed non-Hodgkin lymphoma. Our report illustrates the challenges of an increasingly common infection seen in non-endemic countries, and highlights both daily management dilemmas and associated difficulties that arise.

Visceral leishmaniasis and HIV coinfection in the Mediterranean region.

Visceral leishmaniasis is hypoendemic in Mediterranean countries, where it is caused by the flagellate protozoan Leishmania infantum. VL cases in this area account for 5%–6% of the global burden. Cases of Leishmania/HIV coinfection have been reported in the Mediterranean region, mainly in France, Italy, Portugal, and Spain. Since highly active antiretroviral therapy was introduced in 1997, a marked decrease in the number of coinfected cases in this region has been reported. The development of new diagnostic methods to accurately identify level of parasitemia and the risk of relapse is one of the main challenges in improving the treatment of coinfected patients. Clinical trials in the Mediterranean region are needed to determine the most adequate therapeutic options for Leishmania/HIV patients as well as the indications and regimes for secondary prophylaxis. This article reviews the epidemiological, diagnostic, clinical, and therapeutic aspects of Leishmania/HIV coinfection in the Mediterranean region.

Screening of Imported Infectious Diseases Among Asymptomatic Sub-Saharan African and Latin American Immigrants: A Public Health Challenge

Migrants from developing countries are usually young and healthy but several studies report they may harbor asymptomatic infections for prolonged periods. Prevalence of infections were determined for asymptomatic immigrants from Latin America and sub-Saharan Africa who ettended to a European Tropical Medicine Referral Center from 2000 to 2009. A systematic screening protocol for selected infections was used. Data from 317 sub-Saharan Africans and 383 Latin Americans were analyzed. Patients were mostly young (mean age 29 years); there were significantly more males among sub-Saharan Africans (83% versus 31.6%) and pre-consultation period was longer for Latin Americans (5 versus 42 months). Diagnoses of human immunodeficiency virus (HIV), chronic hepatitis B and C virus infection, and latent tuberculosis were significantly more frequent in sub-Saharan Africans (2.3% versus 0.3%; 14% versus 1.6%; 1.3 versus 0%; 71% versus 32.1%). There were no significant differences in prevalence for syphilis and intestinal parasites. Malaria and schistosomiasis prevalence in sub-Saharan Africans was 4.6% and 5.9%, respectively, and prevalence of Chagas disease in Latin Americans was 48.5%. Identifying and treating asymptomatic imported infectious diseases may have an impact both for the individual concerned and for public health. Based on these results, a systematic screening protocol for asymptomatic immigrants is proposed.

Travelers visiting friends and relatives (VFR) and imported infectious disease: Travelers, immigrants or both? A comparative analysis

INTRODUCTION Immigrants are increasingly traveling back to their countries of origin to visit friends and relatives (VFRs). They account for an important proportion of all international travelers and have a high risk for certain travel-related infectious diseases. METHODS We describe the spectrum of infectious diseases diagnosed in a cohort of 351 VFRs and compare them with two previously published cohorts: of immigrants and travelers attended at our centre. RESULTS The most frequent diagnoses observed among VFRs were typical travel-associated infections such as malaria (75 [21.4%]), travelers diarrhea 17 [4.8%]), intestinal parasites (16 [4.6%]) and dengue (11 [3.1%]). Asymptomatic chronic infectious diseases, such as latent tuberculosis (56 [16%]), chronic viral hepatitis (18 [5.1%]) and filariasis (18 [5.1%]), probably acquired before migration, were also observed. CONCLUSIONS VFRs should thus be approached from two perspectives as concerns imported infectious diseases: as travelers and as immigrants. Etiological studies focusing on the presenting complaint as well as systematic screening for other latent infectious diseases should be performed.

Miltefosine for Visceral and Cutaneous Leishmaniasis: Drug Characteristics and Evidence-Based Treatment Recommendations

Miltefosine is the only recognized oral agent with potential to treat leishmaniasis. Miltefosine had demonstrated very good cure rates for visceral leishmaniasis (VL) in India, Nepal, and Bangladesh, but high rates of clinical failures have been recently reported. Moderate efficacy has been observed for VL in East Africa, whereas data from Mediterranean countries and Latin America are scarce. Results have not been very promising for patients coinfected with VL and human immunodeficiency virus. However, miltefosines long half-life and its oral administration could make it a good option for maintenance prophylaxis. Good evidence of efficacy has been documented in Old World cutaneous leishmaniasis (CL), and different cure rates among New World CL have been obtained depending on the geographical areas and species involved. Appropriate regimens for New World mucocutaneous leishmaniasis need to be established, although longer treatment duration seems to confer better results. Strategies to prevent the development and spread of miltefosine resistance are urgently needed.

Clinical and Epidemiological Characteristics of Imported Infectious Diseases in Spanish Travelers

INTRODUCTION Spain could be a potential area in Europe for the development and spread of emerging diseases from the tropics due to its geoclimatic characteristics, but there is little information on infectious diseases imported by travelers. The aim of this article was to analyze clinical-epidemiological characteristics of infectious diseases imported by Spanish travelers from the tropics. METHODS A retrospective descriptive study of 2,982 travelers seeking medical advice who return ill from the tropics was conducted. Demographic data, details of travel (destination, type, and duration), preventive measures, clinical syndromes, and diagnoses were analyzed. RESULTS Nearly half (46.5%) the travelers had traveled to sub-Saharan Africa; 46.5% reported a stay exceeding 1 month (and almost a quarter more than 6 months). Following pre-travel advice, 69.1% received at least one vaccine and 35.5% took malarial chemoprophylaxis with variations according to geographical area of travel. In all, 58.8% of this took chemoprophylaxis correctly. Most common syndromes were fever 1,028 (34.5%), diarrhea 872 (29.3%), and cutaneous syndrome 684 (22.9%). Most frequent diagnoses were travelers diarrhea (17.2%), malaria (17%), and intestinal parasites (10.4%). The three main syndromes in travelers to the Caribbean-Central America, Indian subcontinent-Southeast Asia, and other areas were diarrhea, fever, and cutaneous syndrome (p < 0.05); in sub-Saharan Africa were fever, cutaneous syndrome, and diarrhea (p < 0.05); and in South America were cutaneous syndrome, diarrhea, and fever (p < 0.05). Travelers to sub-Saharan Africa showed a higher frequency of malaria, rickettsiosis, filariasis, and schistosomiasis (p < 0.05); those to South America showed cutaneous larva migrants, other ectoparasitosis, and cutaneous/mucocutaneous leishmaniasis; and those to the Indian subcontinent-Southeast Asia showed intestinal parasitosis, arboviriasis, and enteric fever (p < 0.05). CONCLUSIONS Increased international travel is a key factor for the development and spread of emerging pathogens. Information on these diseases is essential to establish early warning mechanisms and action plans. Spain represents a unique setting for this.

Evaluation of Nitazoxanide for the Treatment of Disseminated Cystic Echinococcosis: Report of Five Cases and Literature Review

We aimed to evaluate the effectiveness of nitazoxanide in disseminated cystic echinococcosis (DCE) that failed to respond to surgical and antiparasitic therapy. We report on seven patients (five of them with bony involvement): two cases from the literature and five patients who were included in a compassionate trial of nitazoxanide therapy in our hospital. Median follow-up time until nitazoxanide therapy was 12 years and all patients had received prior medical treatment and extensive surgery. Nitazoxanide (500 mg/12 h) in combination with albendazole, with/without praziquantel, was administered for 3-24 months. Three patients improved: one with muscle involvement (clinico-radiological response), one with lung involvement (radiological response), and another with soft tissue and bony involvement (clinico-radiological response of soft tissue cysts). There was one discontinuation after 15 days of starting therapy. Nitazoxanide combination therapy could have a role in the treatment of DCE when there is no bony involvement. Long-term safety profile seems to be favorable.