Imported Mansonella perstans infection in Spain.

BACKGROUND: Mansonella perstans infection can be considered one of the most neglected tropical infectious diseases. Very few studies have reported on the clinical picture caused by infection with this nematode. Therefore, our study was aimed to describe the clinical patterns and treatment of imported M. perstans infection by migrants from Africa. METHODS: The present study evaluated a large cohort of migrants who have been diagnosed, examined and treated for imported M. perstans infection at a Spanish reference center (Hospital Carlos III Tropical Medicine Unit, Madrid, Spain) over a 19-year period. Most patients voluntarily attend the emergency unit or are referred from primary care or general hospitals in Madrid. Chi-square test was used to compare the association between categorical variables. The continuous variables were compared by Student's t-test or the Mann-Whitney test. The corresponding regression models were used for multivariate analysis. RESULTS: Five hundred three cases of migrants from tropical and subtropical areas with M. perstans infection were identified. Two hundred sixty-four patients were female (52.5%). The mean age (± SD) was 44.6 ± 18.2 years (range: 16-93 years). The mean time (± SD) between the arrival in Spain and the first consultation was 8.6 ± 18.0 months. The major origin of the patients was Equatorial Guinea (97.6%). Regarding the clinical picture, 257 patients were asymptomatic (54.7%) and 228 were symptomatic (45.3%); 190 patients had pruritus (37.8%), 50 (9.9%) had arthralgia, 18 patients had Calabar-like swelling (3.6%), and 15 (3%) had abdominal pain. Four hundred forty-two (87.9%) migrants had hyper-IgE, and 340 (67.6%) had eosinophilia. One hundred ninety-five patients had coinfections with other filarial nematodes (38.8%), and 308 migrants had only M. perstans infection (61.2%). Four hundred thirty-seven cases (86.9%) had been treated with anti-filarial drugs; 292 cases were treated with one anti-filarial drug, and 145 cases were treated with combined anti-filarial therapy. Additionally, 20 (4%) cases received steroids and 38 (7.6%) cases received antihistamines. CONCLUSIONS: A long series of M. perstans infections is presented in sub-Saharan immigrants whose data indicate that it should be included in the differential diagnosis in patients with pruritus or analytical alterations such as eosinophilia or hyper-IgE presentation, and they also have a high number of coinfections with other microorganisms whose treatment needs to be protocolized.

Loiasis in sub-Saharan migrants living in Spain with emphasis of cases from Equatorial Guinea.

BACKGROUND: Loiasis is an uncommon and poorly understood parasitic disease outside endemic areas of Africa. The aim of this study was to describe the clinical and biological patterns and treatment of imported loiasis by sub-Saharan migrants diagnosed in Madrid, Spain. METHODS: A retrospective study was conducted with sub-Saharan immigrants seen at the Tropical Medicine Unit of the Carlos III Hospital in Madrid, Spain, a reference center, over 19 years. Categorical variables were expressed as frequency counts and percentages. Continuous variables were expressed as the mean and standard deviation (SD) or median and interquartile range (IQR: Q3-Q1). Chi-square tests were used to assess the association between categorical variables. The measured outcomes were expressed as the odds ratio (OR) with a 95% confidential interval. Continuous variables were compared by Student's t-tests or Mann-Whitney U tests. Binary logistic regression models were used. P <  0.05 was considered a statistically significant difference. RESULTS: One hundred thirty-one migrants from tropical and subtropical areas with loiasis were identified. Forty-nine patients were male (37.4%). The migrants' mean age (±SD) was 42.3 ± 17.3 years, and 124 (94.7%) were from Equatorial Guinea. The median time (IQR) between arrival in Spain and the first consultation was 2 (1-7) months. One hundred fifteen migrants had eosinophilia, and one hundred thirteen had hyper-IgE syndrome. Fifty-seven patients had pruritus (43.5%), and thirty patients had Calabar swelling (22.9%). Seventy-three patients had coinfections with other filarial nematodes (54.2%), and 58 migrants had only Loa loa infections (45.8%). One hundred two patients (77.9%) were treated; 45.1% (46/102) patients were treated with one drug, and 54.9% (56/102) patients were treated with combined therapy. Adverse reactions were described in 14 (10.7%) migrants. CONCLUSIONS: Our patients presented early clinical manifestations and few atypical features. Thus, physicians should systematically consider loiasis in migrants with a typical presentation. However, considering that 72.5% of the patients had only positive microfilaremia without any symptoms, we suggest searching for microfilaremia in every migrant from endemic countries for loiasis presenting with eosinophilia.

Misdiagnosis of Babesiosis as Malaria, Equatorial Guinea, 2014.

We report a case of babesiosis, caused by Babesia microti, in a missionary who worked in Equatorial Guinea but also visited rural Spain. The initial diagnosis, based on clinical features and microscopy, was malaria. The patient's recovery was delayed until she received appropriate treatment for babesiosis.

Dermatological manifestations in onchocerciasis: A retrospective study of 400 imported cases.

INTRODUCTION: Onchocerciasis is caused by Onchocerca volvulus and mainly leads to pruritus and skin and visual disorders, including blindness. Seventeen million people are infected in 38 countries; 31 of these are in sub-Saharan Africa, six in Latin America and one on the Arabian Peninsula. More than 99% of cases occur in sub-Saharan Africa where 120 million people are at risk of infection. Eye disorders have been well-documented; however, skin disorders have not been described accurately. The objective of our study was to describe the epidemiology, main skin manifestations and treatment of imported onchocerciasis. MATERIAL AND METHODS: A retrospective study was thus conducted by analysing the main demographic, clinical and treatment data regarding a cohort of 400 patients attending a reference clinical unit over a 17-year period. RESULTS: Most patients were female (55%) with mean age 37.5±16.7 years. All the migrants came from sub-Saharan countries. The most frequently occurring dermatological symptom was pruritus. Ivermectin had been used as first-line therapy and adverse reactions had been described in 11 patients (3.2%). CONCLUSIONS: The results indicate the fact that there should be a clinical suspicion of onchocerciasis regarding immigrants from endemic areas having skin lesions compatible with the disease's profile or asymptomatic patients having eosinophilia or unexplained high IgE. Moreover, skin snips from the buttocks region were very fruitful and treatment with ivermectin was seen to be safe. This is the largest case series regarding imported onchocerciasis described up to the present time.

Schistosomiasis in European Travelers and Migrants: Analysis of 14 Years TropNet Surveillance Data.

Schistosomiasis remains one of the most prevalent parasitic diseases worldwide and the infection is frequently found in travelers and migrants. The European Network for Tropical Medicine and Travel Health conducted a sentinel surveillance study on imported schistosomiasis between 1997 and 2010. This report summarizes epidemiological and clinical data from 1,465 cases of imported schistosomiasis. Direct pathogen detection and serology were the main diagnostic tools applied. Of these, 486 (33%) cases were identified among European travelers, 231 (16%) among long-term expatriates, and 748 (51%) among non-European immigrants. Overall, only 18.6% of travelers had received pretravel advice; 95% of infections were acquired in the African region. On species level, Schistosoma mansoni was identified in 570 (39%) and Schistosoma haematobium in 318 (22%) cases; 57.5% of patients were symptomatic. Acute symptoms were reported in 27% of patients leading to earlier presentation within 3 months. Praziquantel was used in all patients to treat schistosomiasis. Many infections were detected in asymptomatic patients. In 47.4% of asymptomatic patients infection was detected by microscopy and in 39% by serology or antigen testing. Schistosomiasis remains a frequent infection in travelers and migrants to Europe. Travelers should be made aware of the risk of schistosomiasis infection when traveling to sub-Saharan Africa. Posttravel consultations particularly for returning expatriates are useful given the high potential for detecting asymptomatic infections.

Imported Dengue Infection in a Spanish Hospital with a High Proportion of Travelers from Africa: A 9-Year Retrospective Study.

Epidemiological data on dengue in Africa are still scarce. We investigated imported dengue infection among travelers with a high proportion of subjects from Africa over a 9-year period. From January 2005 to December 2013, blood samples from travelers with clinical suspicion of dengue were analyzed. Dengue was diagnosed using serological, antigen detection, and molecular methods. Subjects were classified according to birthplace (Europeans versus non-Europeans) and last country visited. Overall, 10,307 serum samples corresponding to 8,295 patients were studied; 62% were European travelers, most of them from Spain, and 35.9% were non-Europeans, the majority of whom were born in Africa (mainly Equatorial Guinea) and Latin America (mainly Bolivia, Ecuador, and Colombia). A total of 492 cases of dengue were identified, the highest number of cases corresponding to subjects who had traveled from Africa (N = 189), followed by Latin America (N = 174) and Asia (N = 113). The rate of cases for Africa (4.5%) was inferior to Asia (9%) and Latin America (6.1%). Three peaks of dengue were found (2007, 2010, and 2013) which correlated with African cases. A total of 2,157 of past dengue infections were diagnosed. Non-Europeans who had traveled from Africa had the highest rate of past infection (67.8%), compared with non-Europeans traveling from Latin America (38.7%) or Asia (35%). Dengue infection in certain regions of Africa is underreported and the burden of the disease may have a magnitude similar to endemic countries in Latin America. It is necessary to consider dengue in the differential diagnosis of other febrile diseases in Africa.

Chikungunya virus infections among travellers returning to Spain, 2008 to 2014.

Since the first documented autochthonous transmission of chikungunya virus in the Caribbean island of Saint Martin in 2013, the infection has been reported within the Caribbean region as well as North, Central and South America. The risk of autochthonous transmission of chikungunya virus becoming established in Spain may be elevated due to the large numbers of travellers returning to Spain from countries affected by the 2013 epidemic in the Caribbean and South America, as well as the existence of the Aedes albopictus vector in certain parts of Spain. We retrospectively analysed the laboratory diagnostic database of the National Centre for Microbiology, Institute of Health Carlos III (CNM-ISCIII) from 2008 to 2014. During the study period, 264 confirmed cases, of 1,371 suspected cases, were diagnosed at the CNM-ISCIII. In 2014 alone, there were 234 confirmed cases. The highest number of confirmed cases were reported from the Dominican Republic (n = 136), Venezuela (n = 30) and Haiti (n = 11). Six cases were viraemic in areas of Spain where the vector is present. This report highlights the need for integrated active case and vector surveillance in Spain and other parts of Europe where chikungunya virus may be introduced by returning travellers.

First Report of Babesia microti-Caused Babesiosis in Spain.

Babesiosis is an emerging zoonosis now found in several areas of the world. Using PCR and indirect immunofluorescence assay, we have diagnosed the first case of human babesiosis caused by Babesia microti in Spain. Diagnosis was delayed because of the nonspecific clinical symptoms that occurred in an immunocompetent patient.

Performance of a new gelled nested PCR test for the diagnosis of imported malaria: comparison with microscopy, rapid diagnostic test, and real-time PCR.

Microscopy and rapid diagnostic tests (RDTs) are the techniques commonly used for malaria diagnosis but they are usually insensitive at very low levels of parasitemia. Nested PCR is commonly used as a reference technique in the diagnosis of malaria due to its high sensitivity and specificity. However, it is a cumbersome assay only available in reference centers. We evaluated a new nested PCR-based assay, BIOMALAR kit (Biotools B&M Labs, Madrid, Spain) which employs ready-to-use gelled reagents and allows the identification of the main four species of Plasmodium. Blood samples were obtained from patients with clinical suspicion of malaria. A total of 94 subjects were studied. Fifty-two (55.3%) of them were malaria-infected subjects corresponding to 48 cases of Plasmodium falciparum, 1 Plasmodium malariae, 2 Plasmodium vivax, and 1 Plasmodium ovale. The performance of the BIOMALAR test was compared with microscopy, rapid diagnostic test (RDT) (BinaxNOW® Malaria) and real-time quantitative PCR (qPCR). The BIOMALAR test showed a sensitivity of 98.1% (95% confidence interval [CI], 89.7-100), superior to microscopy (82.7% [95% CI, 69.7-91.8]) and RDT (94.2% [95% CI, 84.1-98.8]) and similar to qPCR (100% [95% CI, 93.2-100]). In terms of specificity, the BIOMALAR assay showed the same value as microscopy and qPCR (100% [95% CI, 93.2-100]). Nine subjects were submicroscopic carriers of malaria. The BIOMALAR test identified almost all of them (8/9) in comparison with RDT (6/9) and microscopy (0/9). In conclusion, the BIOMALAR is a PCR-based assay easy to use with an excellent performance and especially useful for diagnosis submicroscopic malaria.

Imported strongyloidiasis in Spain.

OBJECTIVES: The objective of this study was to assess the epidemiological, laboratory, and clinical features of imported strongyloidiasis in a tropical medicine referral unit in Madrid, Spain. METHODS: This was a retrospective study based on a review of medical records. A patient was diagnosed with strongyloidiasis when the infection could be detected by conventional stool analysis and/or serology against Strongyloides stercoralis, regardless of the presence of symptoms. RESULTS: One hundred and seventy-eight cases of strongyloidiasis were included in the study. Stool tests were performed in all patients, and serology in 160 patients (89.9%). The diagnosis of strongyloidiasis was based on serology only in four patients; 21 patients only had positive stool tests. A third of the total strongyloidiasis cases in this study were travel-related, mainly associated with short trips (<2 months). Only 47.8% of total cases were symptomatic. We found no differences in clinical presentation between immigrants and travelers with strongyloidiasis. CONCLUSIONS: Not only should strongyloidiasis be suspected in symptomatic travelers and immigrants, but it should also be ruled out when elevated IgE levels or eosinophilia are present. Strongyloidiasis can be asymptomatic in HIV patients, but it should be diagnosed and treated before a possible hyperinfection develops.

Hepatitis B, C, and D and HIV infections among immigrants from Equatorial Guinea living in Spain.

A total of 1,220 subjects from Equatorial Guinea living in Spain (median age = 41 years; 453 male and 767 female) was examined for antibodies to human immunodeficiency virus (HIV) and Hepatitis B (HBV), C (HCV), and D (HDV) viruses. Extracted RNA and DNA from the positive samples were used to quantify viral load. The prevalence of HIV antibodies, HCV RNA, and HBV surface antigen (HBsAg) was 10.8% (N = 132), 11.6% (N = 141), and 7.9% (N = 96), respectively. The most prevalent HIV variant was CRF02_AG (38.5%; N = 40). HCV genotype 4 (60%; N = 36) and HBV genotype A3 (32%; N = 8) were the hepatitis variants most frequently found. Superinfection with HDV was seen in 20.9% (N = 24) of HBsAg carriers. A control group of 276 immigrants from other sub-Saharan countries showed similar rates of HIV and HBsAg, although no HCV cases were found. Immigrants constitute a major source of HIV and hepatitis viruses in Spain; therefore, it is important that control measures are intensified.

Imported submicroscopic malaria in Madrid.

BACKGROUND: Submicroscopic malaria (SMM) can be defined as low-density infections of Plasmodium that are unlikely to be detected by conventional microscopy. Such submicroscopic infections only occasionally cause acute disease, but they are capable of infecting mosquitoes and contributing to transmission. This entity is frequent in endemic countries; however, little is known about imported SMM.The goals of this study were two-fold: a) to know the frequency of imported SMM, and b) to describe epidemiological, laboratorial and clinical features of imported SMM. METHODS: A retrospective study based on review of medical records was performed. The study population consisted of patients older than 15 years attended at the Tropical Medicine Unit of Hospital Carlos III, between January 1, 2002 and December 31, 2007. Routinely detection techniques for Plasmodium included Field staining and microscopic examination through thick and thin blood smear. A semi-nested multiplex malaria PCR was used to diagnose or to confirm cases with low parasitaemia. RESULTS: SMM was diagnosed in 104 cases, representing 35.5% of all malaria cases. Mean age (IC95%) was 40.38 years (37.41-43.34), and sex distribution was similar. Most cases were in immigrants, but some cases were found in travellers. Equatorial Guinea was the main country where infection was acquired (81.7%). Symptoms were present only in 28.8% of all SMM cases, mainly asthenia (73.3% of symptomatic patients), fever (60%) and arthromialgias (53.3%). The associated laboratory abnormalities were anaemia (27.9%), leukopaenia (15.4%) and thrombopaenia (15.4%). Co-morbidity was described in 75 cases (72.1%). CONCLUSIONS: Results from this study suggest that imported SMM should be considered in some patients attended at Tropical Medicine Units. Although it is usually asymptomatic, it may be responsible of fever, or laboratory abnormalities in patients coming from endemic areas. The possibility of transmission in SMM has been previously described in endemic zones, and presence of vector in Europe has also been reported. Implementation of molecular tests in all asymptomatic individuals coming from endemic area is not economically feasible. So re-emergence of malaria (Plasmodium vivax) in Europe may be speculated.

Guidelines on the treatment of chronic coinfection by Trypanosoma cruzi and HIV outside endemic areas.

As a result of population migration, Chagas disease is no longer limited to the North and South American continents. In HIV-infected patients, chronic infection by Trypanosoma cruzi behaves as an opportunistic infection in severely immunosuppressed patients and is responsible for high morbidity and mortality. Unlike other opportunistic infections, information on the natural history, diagnosis, treatment, and prevention of Chagas disease is scarce. Spain has the highest number of cases of Chagas disease outside the North and South American continents, and coinfection with HIV is increasingly prevalent. In this article, the Spanish Society for Tropical Medicine and International Health (Sociedad Española de Medicina Tropical y Salud Internacional) reviews the current situation of coinfection with HIV and T. cruzi infection and provides guidelines on the diagnosis, treatment, and prevention in areas where Chagas disease is not endemic. It also identifies areas of uncertainty where additional research is necessary.

Recommendations for management of Chagas disease in organ and hematopoietic tissue transplantation programs in nonendemic areas.

The substantial immigration into Spain from endemic areas of Chagas disease such as Latin America has increased the number of potential donors of organs and tissues. In addition, an increasing number of patients with advanced Chagas heart disease may eventually be eligible to receive a heart transplant, a universally accepted therapeutic strategy for the advanced stages of this disease. Therefore, it is necessary to establish protocols for disease management. This document is intended to establish the guidelines to be followed when a potential donor or a tissue or organ recipient is potentially affected by Chagas disease and summarizes the action criteria against the possibility of Chagas disease transmission through the donation of organs, tissues, or hematopoietic stem cells and aims to help professionals working in this field. A single registry of transplants in Trypanosoma cruzi infected donors and/or recipients will provide and disseminate experience in this area, which has shown a low recorded incidence to date.

Molecular surveillance of circulating dengue genotypes through European travelers.

BACKGROUND: Dengue viruses (DENV) are the most widespread arthropod-borne viruses, which have shown an unexpected geographic expansion, as well as an increase in number and severity of outbreaks in the last decades. Although the emergence of dengue is considered to be due to a number of complex factors, epidemiological studies have shown that some strains of dengue might be associated with increased severity and higher transmission rates than others. In this context, surveillance and identification of the appearance or introduction of more virulent strains, along with fluctuation of DENV among endemic areas are now considered essential public health activities. METHODS: Samples from travelers returning from the tropics with acute dengue infections were analyzed to obtain up-dated information on circulating dengue strains. A short nucleotide fragment located in the carboxyl terminus of the dengue E gene was used for the characterization of DENV strains and the identification of their sero- and genotype. RESULTS: One hundred eighty-six new dengue strains have been classified into 12 distinct genotype groups within the four dengue serotypes. The identification of the emergence of different sero- and genotypes, the appearance of new clades correlating with outbreaks, and the identification of a dengue-4 genotype not previously reported have been achieved. Interestingly, African strains characterized in this study have provided valuable data on dengue circulation on the continent. CONCLUSIONS: This work demonstrates the convenience of routine application of molecular epidemiology analyses in dengue diagnosis laboratories. The use of molecular epidemiology tools on the analysis of imported dengue infections strengthens data acquisition on dengue strain movements correlating with epidemiological changes. The importance of surveillance of imported diseases contributing data for the epidemiological knowledge of infectious diseases in endemic areas has been once more demonstrated.

Detection of hepatitis B virus genotype A3 and primary drug resistance mutations in African immigrants with chronic hepatitis B in Spain.

BACKGROUND: Universal vaccination and antiviral therapy have reduced chronic hepatitis B virus (HBV) in natives in the Western world. However, immigration from high HBV endemic areas continues to maintain a relatively stable prevalence of chronic hepatitis B in most developed countries. METHODS: All foreigners attending a referral infectious diseases department in Madrid, Spain, from January 2007 to December 2008, were evaluated for serum HBV surface antigen (HBsAg). Positive cases underwent further virological characterization. RESULTS: A total of 1718 foreigners were examined, of whom 1322 (77%) were sub-Saharan Africans. Serum HBsAg was positive in 121 (7%), HIV in 135 (7.9%) and hepatitis C virus antibodies in 212 (12.3%). HBV subgenotype A3, which so far had only been reported in people originating from Cameroon, was found in nearly half (14/29) of the tested specimens with detectable serum HBV-DNA. Interestingly, the lamivudine resistance mutation rtM204V was found in two Africans (6.9%), one infected with HBV-A3 and the other with HBV-E. Lack of prior exposure to antiviral therapy in these two patients was confirmed retrospectively. CONCLUSIONS: Circulation of uncommon HBV variants, including strains with primary drug resistance, may follow large immigrant flows from HBV endemic regions to Western countries. Close surveillance of this population is warranted, as early diagnosis and early antiviral therapy may reduce transmission and prevent clinical complications.

Changing rate of non-B subtypes and coinfection with hepatitis B/C viruses in newly diagnosed HIV type 1 individuals in Spain.

Immigration from developing regions to Western countries has resulted in an increased rate of non-B subtypes in the HIV population. However, it is unclear whether these HIV variants remain confined to foreigners or are already spreading among natives. Since many immigrants come from regions in which hepatitis B virus (HBV) and hepatitis C virus (HCV) are endemic, HIV-hepatitis coinfection might be more frequent in newly diagnosed HIV persons. Herein, we report changes in the prevalence and distribution of HIV-1 subtypes in Madrid, Spain over the past 10 years as well as the rate of chronic HBV and HCV coinfection in 1854 newly diagnosed HIV-1 individuals. Overall 18.2% carried HIV-1 non-B subtypes, although the prevalence increased over time reaching a peak of 19.4% in the last period (2007-2010). The most common non-B variants were CRF02_AG (37%), G (12%), A (9.9%), and C (7.8%). In native Spaniards the rate of non-B subtypes increased from 1.5% in 2000-2002 to 7.2% in 2003-2006 and to 11.4% in 2007-2010 (p = 0.04). Chronic hepatitis B and C were found, respectively, in 4.2% and 8.3% of the study population. While the prevalence of chronic hepatitis B has remained fairly stable over time across distinct populations, the rate of chronic HCV infection has experienced a significant decline, mainly in native Spaniards as a result of a reduction in intravenous drug use. In summary, the prevalence of HIV-1 non-B subtypes is rising in newly diagnosed HIV-1 individuals in Spain, including the native population. In contrast, the rate of HBV coinfection remains unchanged and the rate of HCV coinfection has declined.

First diagnosis of an imported human myiasis caused by Hypoderma sinense (Diptera: Oestridae), detected in a European traveler returning from India.

This paper reports a case of myiasis caused by Hypoderma sinense in a European man returning from a journey through northern India. The patient showed eosinophilia, systemic signs of inflammation, and painful swellings in several parts of the body. The diagnosis was confirmed by specific serology and parasite molecular identification.