Miriam Navarro

Imported infectious diseases in mobile populations, Spain.

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

The BENEFIT Trial: Where Do We Go from Here?

In the next five years, we can now project that 200,000 people living with Chagas disease will die from heart disease and related complications. We urgently need to redouble our efforts to identify and treat young people who are still in the early stages of their illness, but ultimately we need to find better treatments and new cures. According to recent estimates, there are 5.7–9.4 million people living with Chagas disease (American trypanosomiasis caused by Trypanosoma cruzi), a neglected tropical disease and leading cause of heart disease and cardiomyopathy, especially in Latin America and the United States [1,2]. Today, less than 1% of people infected with T. cruzi have access to diagnosis and treatment [3], a consequence of the fact that Chagas disease mostly affects those living in extreme poverty and in marginal surroundings. This finding is especially sad given new information by the World Health Organization (WHO) stating that more than one-half of Chagas disease sufferers live in Latin America’s three wealthiest countries—Argentina, Brazil, and Mexico [1]. Moreover, there are hundreds of thousands of infected people living in the US, with emerging evidence for significant T. cruzi transmission in Texas [4,5]. In this sense, Chagas disease represents one of the Western Hemisphere’s greatest health disparities. Moreover, in recent years we also have seen the globalization of Chagas disease to Spain and elsewhere in Europe and worldwide [6]. For years, the community of scientists, physicians, and other health care providers and Chagas disease patients has been awaiting the results of the Benznidazole Evaluation for Interrupting Trypanosomiasis (BENEFIT) trial, which was designed to evaluate the safety and efficacy of benznidazole in patients with Chagasic cardiomyopathy [7]. Approximately 20%–30% of T. cruzi-infected individuals progress to Chagasic cardiomyopathy, a debilitating heart condition associated with conduction disturbances, heart failure, and sudden death. While it is established that benznidazole is effective in curing Chagas disease patients during their early acute phase [8–11], very few individuals are diagnosed at this stage of the disease. The BENEFIT trial aimed to determine if the 1.17 million people now living with Chagasic cardiomyopathy (WHO estimate [1]) might also experience improved clinical outcomes or even cures with benzimidazole treatment. Unfortunately, the answer appears to be “no.” Compared to a placebo control, benznidazole did not result in a statistically significant improvement in cardiac clinical outcomes. Although the study was not sufficiently powered to show incremental benefits in cardiac outcome (on the order of 5%–15%), it is clear that our current strategies for antiparasitic chemotherapy need to be revisited for patients with evidence of Chagasic heart disease. But there is additional bad news—the BENEFIT trial found that in both treated and placebo arms (comprising almost three thousand patients), 17%–18% died over a five-year time frame, most from cardiac complications [7]. If we extrapolate from the WHO estimate, this means that roughly 200,000 people will die from Chagasic cardiomyopathy over the next five years. To put this number in perspective, it is almost identical to the number of women living in the US who will die from breast cancer over the same period [12]. Whereas breast cancer is now linked with a highly successfully and accomplished advocacy and awareness campaign that promotes early detection and treatment, as well as research and development (R&D) into an exciting portfolio of new and innovative therapies, we are now facing almost the opposite situation with Chagas disease and cardiomyopathy. Today, there are few advocates for the millions of Chagas disease sufferers mostly living in poor and marginalized conditions. As a result, the vast majority have no access to diagnosis and treatment, and far too little is invested into R&D for new drugs, vaccines, and other tools (including tests for cure). From our perspective, the BENEFIT trial is a wake-up call to aggressively pursue a global initiative of diagnosis, treatment, and research, emphasizing the following specific points:

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.

Clostridium difficile–Associated Diarrhea after Antibiotic Treatment for Traveler's Diarrhea

Diarrhea commonly affects international travelers. Episodes are usually short-lasting, but in some patients, symptoms may persist. Clostridium difficile infection should be excluded in travelers with prolonged disease. We report what is, to our knowledge, the first reported study of patients with C. difficile-associated diarrhea after receipt of antibiotic treatment for travelers diarrhea.

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.

Visceral larva migrans in immigrants from latin america.

To determine whether increased migration is associated with an increase in incidence of toxocariasis (visceral larva migrans), we analyzed clinical data obtained from immigrants from Latin America. Although infection with Toxocara sp. roundworm larvae is distributed worldwide, seroprevalence is highest in tropical and subtropical areas.

Clinicoepidemiological characteristics of HIV-infected immigrants attended at a tropical medicine referral unit.

BACKGROUND Migration is a growing phenomenon with a well-known impact in infectious diseases epidemiology. Currently, immigrants represent almost 10% of the Spanish population. The majority come from countries where the prevalence of chronic viral illnesses is higher than in Spain. METHODS To describe clinicoepidemiological features of human immunodeficiency virus (HIV)-infected immigrants attending our Unit and to compare differential characteristics depending on geographical origin, information from all new immigrants from January 1997 to December 2006 was collected. STUDY DESIGN noninterventional retrospective chart review. RESULTS We screened 1,609 patients of whom 77 (4.8%) were HIV antibody (Ab) positive. Of these, 80% were sub-Saharan Africans (SSAFR) and 20% were South-Central Americans (SCA). HIV prevalence was higher in SSAFR (5.6% vs 3.2%; p= 0.04). Overall, of those who were HIV Ab positive, 70% were male (median age 30 years), 59% heterosexuals, 9% hepatitis C virus coinfected, 8.6% hepatitis B virus coinfected, and 34% showed a positive tuberculin skin test. Median CD4 cell count was 263 cells/microL, median HIV-ribonucleic acid viral load 4.6 Log/mL, and 48% had a late diagnosis [acquired immunodeficiency syndrome (AIDS)-defining illness or <200 CD4 microL at the time of diagnosis]. Only 68% of patients for whom antiretroviral therapy was indicated actually started therapy and 22% were lost to follow-up just after diagnosis. SCA had lower CD4 cell counts (26 vs 168 cells/microL; p= 0.016), higher viral loads (5.3 vs 4.8 Log; p= 0.001), and were more likely to have an AIDS-defining illness (53% vs 21%; p= 0.04) compared to SSAFR. Tuberculin skin test reactivity was more common among SSAFR versus SCA [adjusted by CD4 count, odds ratio (OR) 6.3 and 95% confidence interval (CI): 0.65-60.5]. The main risk factor for late diagnosis was geographical origin: OR 4.6 (95% CI: 1.11-19.3) (SCA vs SSAFR; adjusted by the interval between the date of arrival in Spain and the date of HIV diagnosis). CONCLUSIONS Almost half the HIV-infected immigrants were diagnosed in late stages. Patients were frequently lost to follow-up, and a significant minority did not start highly active antiretroviral therapy when indicated. SCA seem to have more severe immunosuppression at the time of diagnosis than SSAFR. Early voluntary routine HIV screening should be promoted.

Reluctance to Do Blood Testing Limits HIV Diagnosis and Appropriate Health Care of Sub-Saharan African Migrants Living in Spain

This study investigates the reasons why sub-Saharan African migrants (SSAM) living in Spain may be unwilling to have their blood tested. A qualitative study was developed for 3 years (2006–2009) with the participation of 1338 SSAM. Cultural differences along with lack of information about Spanish health care system and health-related rights produced a feeling of mistrust towards medical staff. Reluctance to do blood testing may prevent SSAM from having a prompt HIV diagnosis and an appropriate health care. Linguistically and culturally adapted information is essential to overcome these barriers and achieve an equal access to health care services and HIV testing.

Short Course Combination Therapy for Giardiasis after Nitroimidazole Failure

Recommended first line treatments for giardiasis include the nitroimidazoles and, recently, nitazoxanide. For refractory cases, a combination of two or more drugs may be a viable approach. A review of 10 patients with giardiasis refractory to nitroimidazoles with response to a short course (< 2 weeks), combined treatment is presented.

Benznidazole shortage makes chagas disease a neglected tropical disease in developed countries: data from Spain.

Chagas disease is a neglected tropical disease endemic in Latin America. The first-line treatment option is benznidazole, but stocks are expected to run out in the coming months. Spain would need around 5 million benznidazole tablets. This drug shortage could make Chagas disease a neglected tropical disease also in developed countries.