The Use of Quinacrine in Nitroimidazole-resistant Giardia Duodenalis: An Old Drug for an Emerging Problem.

Background: There is little evidence regarding the management of refractory giardiasis after treatment with nitroimidazoles. This study estimates the proportion of persistent giardiasis in 3 hospitals in Barcelona, describes associated risk factors and genotype, and evaluates the efficacy rate of quinacrine in those with persistent giardiasis. Methods: A clinical, prospective, observational study was conducted in patients with giardiasis treated with nitroimidazoles. Those with persistent giardiasis were provided quinacrine. Molecular characterization of Giardia isolates was performed by polymerase chain reaction amplification of a fragment of tpi and bg genes. Results: Seventy-seven patients were recruited and treated with nitroimidazoles, and in 14 of 71 (20%) of patients followed up, Giardia persisted. Refractory giardiasis was associated with malaise (P = .007) and anorexia (P = .02), with previous giardiasis (P = .03), and with previous antibiotic (P = .02) or antiparasitic(P = .04) use. Quinacrine had an effectiveness rate of 100% in refractory giardiasis (n = 13; 95% confidence interval = 75-100). Molecular characterization showed that 17 (25%) Giardia isolates belonged to assemblage A, and 31 (43%) belonged to assemblage B. In refractory giardiasis, assemblage A and B were found responsible in 4 and 6 cases, respectively. Conclusions: Almost 20% of patients presented persistent giardiasis, belonging to both assemblages A and B, after nitroimidazole. Short course of quinacrine was effective in treating refractory cases. Further controlled studies should evaluate its efficacy and safety.

Controlling congenital and paediatric chagas disease through a community health approach with active surveillance and promotion of paediatric awareness.

BACKGROUND: Chagas disease (CD) is endemic in countries of continental Latin America. Congenital transmission is a major concern worldwide. In 2010, the Public Health Agency of Catalonia (ASPCAT) launched a screening protocol for Trypanosoma cruzi infection in pregnant women and their newborns. In 2012, ASPCAT detected appropriate follow-up of pregnant women but incomplete information about their offspring. METHODS: The PROSICS community health team carried out active surveillance and community health action in target populations. These activities included active case searches, group awareness workshops and visualization campaigns as well as investigation of all lost children born from pregnant women with CD and their families. RESULTS: Overall, 42/179 (23.5%) cases were included in the study: 35/42 (83.3%) children were born in Hospitalet de Llobregat (Catalonia, Spain); 4/42 (16.7%) were born in Latin America; two were miscarried and one was stillborn. The mean age of pregnant women was 31.3 years (SD 5.52; range: 21-44): 90.5% were Bolivian, of whom 74% were diagnosed with CD during pregnancy. Of the 35 newborns, 31 were recovered by community health action; 12/31 were correctly controlled at Hospitalet de Llobregat and 19/31 were controlled at a primary health centre. Of these 19 (73.7%) cases, 14 were not tested for CD by family paediatricians and were recovered by the PROSICS community health team. Finally, two (6.9%) of the 29 newborns tested with serology were positive. CONCLUSIONS: It is essential to implement active surveillance, education and information activities at paediatric primary care and community levels to avoid the loss of CD-infected mothers and their newborns. Training sessions addressed to paediatricians and other involved health professionals would consolidate surveillance and care reference circuits, improving the control of congenital CD.

Randomized trial of posaconazole and benznidazole for chronic Chagas' disease.

BACKGROUND: Current therapeutic options for Chagas' disease are limited to benznidazole and nifurtimox, which have been associated with low cure rates in the chronic stage of the disease and which have considerable toxicity. Posaconazole has shown trypanocidal activity in murine models. METHODS: We performed a prospective, randomized clinical trial to assess the efficacy and safety of posaconazole as compared with the efficacy and safety of benznidazole in adults with chronic Trypanosoma cruzi infection. We randomly assigned patients to receive posaconazole at a dose of 400 mg twice daily (high-dose posaconazole), posaconazole at a dose of 100 mg twice daily (low-dose posaconazole), or benznidazole at a dose of 150 mg twice daily; all the study drugs were administered for 60 days. We assessed antiparasitic activity by testing for the presence of T. cruzi DNA, using real-time polymerase-chain-reaction (rt-PCR) assays, during the treatment period and 10 months after the end of treatment. Posaconazole absorption was assessed on day 14. RESULTS: The intention-to-treat population included 78 patients. During the treatment period, all the patients tested negative for T. cruzi DNA on rt-PCR assay beyond day 14, except for 2 patients in the low-dose posaconazole group who tested positive on day 60. During the follow-up period, in the intention-to-treat analysis, 92% of the patients receiving low-dose posaconazole and 81% receiving high-dose posaconazole, as compared with 38% receiving benznidazole, tested positive for T. cruzi DNA on rt-PCR assay (P<0.01 for the comparison of the benznidazole group with either posaconazole group); in the per-protocol analysis, 90% of the patients receiving low-dose posaconazole and 80% of those receiving high-dose posaconazole, as compared with 6% receiving benznidazole, tested positive on rt-PCR assay (P<0.001 for the comparison of the benznidazole group with either posaconazole group). In the benznidazole group, treatment was discontinued in 5 patients because of severe cutaneous reactions; in the posaconazole groups, 4 patients had aminotransferase levels that were more than 3 times the upper limit of the normal range, but there were no discontinuations of treatment. CONCLUSIONS: Posaconazole showed antitrypanosomal activity in patients with chronic Chagas' disease. However, significantly more patients in the posaconazole groups than in the benznidazole group had treatment failure during follow-up. (Funded by the Ministry of Health, Spain; CHAGASAZOL ClinicalTrials.gov number, NCT01162967.).

Epidemiology of imported malaria among children and young adults in Barcelona (1990-2008).

BACKGROUND: Increasing international travel and migration is producing changes in trends in infectious diseases, especially in children from many European cities. The objective of this study was to describe the epidemiology and determine the trends of imported malaria in patients under 20 years old in the city of Barcelona, Spain, during an 18-year period. METHODS: The study included malaria cases that were laboratory confirmed and reported to the malaria register at the Public Health Agency of Barcelona from 1990 to 2008, residing in Barcelona and less than 20 years old. Patients were classified as natives (born in Spain) or immigrants. Differences in the distribution of demographic, clinical characteristics, and incidence per 100,000 person-year evolution were analysed. Natives and immigrants were compared by logistic regression by calculating the odds ratio (OR) with a 95% confidence interval (CI) and Chi-square for a linear trend (p<0.05). RESULTS: Of the total 174 cases, 143 (82.1%) were immigrants, 100 (57.5%) were female, 121 (69.5%) Plasmodium falciparum, and 108 (62.1%) were visiting friends and relatives (VFR) as the reason for travel. Among the immigrants, 99 (67.8%) were from Equatorial Guinea. Immigrant cases more frequently travelled to Africa than natives (p=0.02). The factors associated with imported malaria among immigrant residents was travelling for VFR (OR: 6.2 CI 1.9-20.2) and age 15-19 (OR: 3.7 CI 1-13.3). The incidence increased from 1990 to 1999 (p<0.001) and decreased from 2000 to 2008 (p=0.01), although the global linear trend was not statistically significant (p=0.41). The fatality rate was 0.5%. CONCLUSIONS: The majority of cases of malaria in population less than 20 years in Barcelona were immigrants, travelling to Africa for VFR and Plasmodium falciparum was most frequently detected. The trend analysis of the entire study period did not show a statistically significant decline. It is recommended to be aware of malaria, especially among children of immigrants who travel to their parent's home country for VFR. Better access to pre travel advice should be provided.

Imported malaria among African immigrants: is there still a relationship between developed countries and their ex-colonies?

BACKGROUND: The objective of this study was to compare cases of imported malaria originating from the Spanish ex-colony of Equatorial Guinea (EG) with those originating from the rest of Africa (RA). METHODS: All the African cases detected in Barcelona between 1989 and 2007 were investigated in a retrospective analysis. Clinical-epidemiological variables such as sex, age, visiting friends and relatives (VFR), species, hospital admission and chemo-prophylaxis were compared. Data were analysed by logistic regression, calculating the Odds Ratio (OR) and 95% Confidence Intervals (95% CI). RESULTS: Of the 489 African patients, 279 (57,1%) had been born in EG and 210 (42,9%) in the rest of Africa. The cumulative incidence of imported malaria among those from EG was 179.6 per thousand inhabitants, while in those from the RA it was 33.7 per thousand (p < 0.001). Compliance with chemoprophylaxis (CP) was very low, but there were no differences between the two groups. Comparing those from EG to those from RA, the former were characterized by having more patients in the visiting friends and relatives (VFR) category, and more individuals younger than 15 years or older than 37 years, and more women. They also visited a traveller's health centre more often, had fewer hospital admissions and were less likely to reside in the inner city. CONCLUSION: Cases of imported malaria originating in Africa, are more likely to come from the Spanish ex-colony of EG, and VFR are more likely to be affected. It is recommended that developed countries promote prevention programmes, such as CP advice directed at African immigrants, and develop programmes of cooperation against malaria in their ex-colonies.

Imported malaria in a cosmopolitan European city: a mirror image of the world epidemiological situation.

BACKGROUND: International travel and migration have been related with an increase of imported malaria cases. There has been considerable immigration to Barcelona from low-income countries (LIC) in recent years. The objective is to describe the epidemiology and to determine the trends of the disease in Barcelona. METHODS: Analysis of the cases notified among city residents between 1989 and 2005. Patients were classified as: tourists, voluntary workers, resident immigrants (visiting friends and relatives, VFR) and recently arrived immigrants. An analysis was conducted using the chi2 test and comparison of means. As a measure of association we calculated the Relative Risk (RR) and Odds Ratio (OR) with a Confidence Interval of 95% (CI) and carried out a trends analysis. RESULTS: Of the total of 1,579 imported cases notified, 997 (63.1%) lived in Barcelona city, and 55.1% were male. The mean age of patients was 32.7 years. The incidence increased from 2.4 cases/100,000 in 1989 to 3.5 cases/100,000 in 2005 (RR 1.46 CI:1.36-1.55). This increase was not statistically significant (trends analysis, p = 0.36). In terms of reason for travelling, 40.7% were VFR, 33.6% tourists, 12.1% voluntary workers and 13.6% were recently arrived immigrants. The most frequent species found was Plasmodium falciparum (71.3%), mainly in visitors to Africa (OR = 2.3, CI = 1.7-3.2). The vast majority (82.2%) had had some contact with Africa (35.9% with Equatorial Guinea, a Spanish ex-colony) and 96.6% had not completed chemoprophylaxis. Six deaths were observed, all tourists who had travelled to Africa and not taken chemoprophylaxis (3.9% fatality rate). CONCLUSION: Over the period studied there is an increase in malaria incidence, however the trend is not statistically significant. Lack of chemoprophylaxis compliance and the association between Africa and P. falciparum are very clear in the imported cases. Most of the patients with malaria did not take chemoprophylaxis.

Communicable diseases in the immigrant population attended to in a tropical medicine unit: epidemiological aspects and public health issues.

For geographical and historical reasons, Spain is receiving an increasing number of immigrants. The aim of this study was to evaluate some epidemiological aspects and the main public health issues of communicable diseases in Barcelona's immigrant population. From 2001 to 2004, a population of immigrants from tropical, subtropical regions and Eastern Europe was attended to in our centre. Each patient was offered a complete screening for tropical and common diseases. The prevalence and demographical characteristics of eight diseases with a potential risk of transmission in our setting were studied: latent and active tuberculosis, syphilis, human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV), Chagas disease, Giardia intestinalis and Entamoeba histolytica/Entamoeba dispar. In all, 2464 immigrants mainly from sub-Saharan Africa were seen. Among the patients who underwent the screening, 46.5% had a positive tuberculin skin test (>or=10 mm), incidence of active tuberculosis was 324.7/100,000 immigrants in the period of the study, 6.4% had a positive syphilis serology, 7.7% had a positive HBsAg, 3.1% had a positive serology for HCV and 2.8% were HIV positive, 41 patients from Latin America with risk factors for American Trypanosomiasis were screened for Chagas disease by immunofluorescence assay and 34% had a positive result; 5.4% of stools parasitological tests were positive for G. intestinalis; 4.2% for E. histolytica/E. dispar. Communicable diseases in immigrant population could lead to emerging and re-emerging infections in the European Union with important issues for public health. European countries may have to establish guidelines for screening of infectious diseases in immigrants from low-income countries.