Screening of imported malaria infection in asymptomatic migrants from Sub-Saharan Africa: A retrospective analysis of a 2010-2019 cohort.

BACKGROUND: Up to 40% of cases of imported malaria in Europe are diagnosed in recently arrived migrants, who generally exhibit asymptomatic or mild symptoms and show low parasitaemia (submicroscopic). The study describes the prevalence of malaria infection among asymptomatic Sub-Saharan African migrants (ASSAM) and compares asymptomatic malaria-infected (AMI) vs non-malaria infected patients. METHODS: An observational, comparative, retrospective study was carried out in ASSAM who underwent a medical examination, between 2010 and 2019 at the National Reference Unit for Tropical Diseases (NRU-Trop) in Madrid, Spain. Medical examination and systematic screening protocol for infectious diseases, including screening for malaria infection by Polymerase Chain Reaction (PCR) was performed. RESULTS: During the study period, 632 out of 1061 ASSAM were screened for malaria, median age: 24 years (IQR:1-5); median time from arrival to diagnosis: 2 months (IQR:1-5). P. falciparum was the most frequent species: 61 patients (67.8%). Compared to non-malaria infected, AMI subjects had: higher rate of co-infection with S. stercoralis (41.1%VS 22.9%;p < 0.001) and filariae (8.9% VS 2.4%;p = 0.006), lower erythrocyte corpuscular volume (83.6 VS 84.4;p = 0.008) and lower levels of cholesterol (151.0 VS 167.3;p < 0.001). CONCLUSIONS: We observed a high prevalence of AMI among ASSAM. This highlights the need to consider routing screening of migrants from endemic areas and to study if such screening could avoid the potential morbidities associated with chronic infection, reduce morbi-mortality of acute malaria and the risk of transmission in host communities.

Critical analysis of Chagas disease treatment in different countries.

As a result of globalization and constant migratory flows, Chagas disease is now present in almost all continents. The management and treatment of the disease is often influenced by the economic and social context of the societies that host patients. In this manuscript, we aim to provide a comparative review of approaches to patients with Chagas disease in the Americas and Europe.

Critical analysis of Chagas disease treatment in different countries

As a result of globalization and constant migratory flows, Chagas disease is now present in almost all continents. The management and treatment of the disease is often influenced by the economic and social context of the societies that host patients. In this manuscript, we aim to provide a comparative review of approaches to patients with Chagas disease in the Americas and Europe.

Seroprevalence of vaccine-preventable and non-vaccine-preventable infections in migrants in Spain.

BACKGROUND: Updated seroprevalence studies of infections in migrants may aid the design of tailored vaccination and prevention programmes. The objective of this study was to describe the seroprevalence rates for potentially transmissible viral infections in migrants attended at a referral centre in a major European city. METHODS: Descriptive analysis of seroprevalence of vaccine-preventable and non-vaccine-preventable infections in migrants attended at a centre in Madrid, Spain (2018-19). Recorded variables included age, gender, country of birth/continent of origin, time from arrival to Spain until first clinic visit, rubella, measles, mumps, varicella (VZV), hepatitis B virus (HBV), hepatitis A virus (HAV), hepatitis C virus (HCV) and HIV serology. RESULTS: In total, 468 patients were included, 135 females (28.8%) and 333 males (71.2%), mean age 30.4 years. The majority of patients were from Africa (52.5%, of which 88.2% from sub-Saharan Africa), followed by Latin America (38.5%) and other areas (9%). Seroprevalence for tested migrants for rubella, measles and mumps was < 95% in the group overall (91% rubella, 88% measles, 83% mumps) and lower rates were observed in migrants >20 years (compared with those ≤ 20 years). Over 10% of females were potentially susceptible (negative/indeterminate serology) to rubella (11.4%), measles (12.7%) or mumps (10.3%). Lowest rates of rubella seropositivity were in Latin American migrants (over 12% potentially susceptible); measles and mumps seropositivity was lowest in migrants from areas other than Africa/Latin America (74% and 68%, respectively). Seroprevalence rates were 91% for VZV, 90% overall for HAV, ~6% for HBV chronic infection (~50% of migrants tested susceptible), 2% for HCV and 6% for HIV. CONCLUSIONS: Differences in seroprevalence for vaccine-preventable and transmissible infections according to gender, age range and area of origin were observed. Tailored screening, vaccination and prevention strategies in potentially vulnerable migrant groups should be designed.

COVID-19 and geographical area of origin.

OBJECTIVES: To describe and compare the main clinical characteristics and outcome measures in hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) according to geographical area of origin. METHODS: A retrospective analysis of patients hospitalized with confirmed COVID-19 at a referral centre in Madrid, Spain, during March-May 2020 was performed. Recorded variables (age, gender, intensive care unit (ICU) admission, outcome), and geographical area of origin were compared for Europeans and non-Europeans (Latin Americans, Asians and Africans). RESULTS: In total, 2345 patients with confirmed COVID-19 hospitalized during the study period were included in the study. Of these, 1956 (83.4%) were European and 389 (16.6%) were non-European (of whom over 90%, 354/389, were Latin American). Non-Europeans were significantly younger than Europeans (mean 54 (SD 13.5) versus 70.4 (SD 15.1) years, p < 0.001); the majority were male (1420/2345, 60.6%), with no significant differences in gender between Europeans and non-Europeans (1197/1956 (61.2%) male in the European group versus 223/389 (57.3%) male in the non-European group, p 0.15). In-hospital mortality overall was higher in Europeans (443/1956, 22.7%) than in non-Europeans (40/389, 10.3%) (p < 0.001), but there were no significant differences when adjusted for age/gender (OR 1.27, 95% CI 0.86-1.88). Non-Europeans were more frequently admitted to ICU (71/389, 18.3%) compared with Europeans (187/1956, 9.6%) (p < 0.001) and a difference in ICU admission rate was also found when adjusted for age/gender (OR 1.43, 95% CI 1.03-1.98). CONCLUSIONS: No significant differences in mortality were observed between Europeans and non-Europeans (mainly Latin Americans), but an increase in ICU admission rate was found in non-Europeans.

Imported Arbovirus Infections in Spain, 2009-2018.

To determine the epidemiologic and clinical characteristics of patients in Spain with imported arbovirus infections, we analyzed 22,655 records from a collaborative network for January 2009-December 2018. Among 861 arbovirus infections, 845 were monoinfections (456 [53%] dengue, 280 [32.5%] chikungunya, 109 [12.7%] Zika) and 16 (1.8%) were co-infections. Most patients were travelers (56.3%) or immigrants returning to Spain after visiting friends or relatives (31.3%). Median patient age was 37 years; most (62.3%) were women and some (28.6%) had received pretravel advice. Only 12 patients were immunosuppressed. Six cases (all dengue monoinfections, none in immunosuppressed patients) were severe. Since 2014, nondengue arbovirus infections increased; until 2016, chikungunya and Zika were most common. Imported arbovirus infections (mostly dengue) were frequently diagnosed, although increased chikungunya and Zika virus infections coincided with their introduction and spread in the Americas. A large proportion of cases occurred in women of childbearing age, some despite receipt of pretravel advice.

Update on the major imported protozoan infections in travelers and migrants.

Globalization has contributed to the emergence of specific parasitic diseases in novel geographical areas, and in these regions, these infections in travelers and immigrants may cause a considerable burden of disease. Timely diagnosis and treatment of protozoan infections to decrease mortality and prevent associated complications are essential. In this respect, the increased availability of specific DNA-detection procedures has improved the diagnosis of many imported parasitic infections. Travelers and immigrants with associated comorbidities or immunosuppression may pose a special challenge regarding management. An updated review of the main protozoan infections in mobile populations (malaria, Chagas disease, leishmaniasis, enteric protozoan infections) is provided, focusing on the changing epidemiology of these diseases, recent developments in diagnosis and management and the possibility of local transmission of imported infections.

Imported strongyloidiasis: Data from 1245 cases registered in the +REDIVI Spanish Collaborative Network (2009-2017).

BACKGROUND: Imported strongyloidiasis is increasingly being diagnosed in non-endemic areas. The aim of this study was to describe the epidemiological, clinical and microbiological characteristics of patients with imported strongyloidiasis in Spain. METHODOLOGY: This is an observational retrospective study that included all patients diagnosed of strongyloidiasis registered in the +REDIVI Collaborative Network from 2009 to 2017. Demographic, epidemiological and clinical information was collected from the +REDIVI database, and extra information regarding microbiological techniques, treatment and follow-up was requested to participant centers. FINDINGS: Overall, 1245 cases were included. Most of them were immigrants (66.9%), and South America was the most frequent area of origin. Detection of larvae in stool samples was observed in 21.9% of the patients, and serological tests allowed making the diagnosis in the rest of the cases. Eosinophilia was present in 82.2% of cases. Treatment with ivermectin (compared with albendazole) was the most strongly associated factor to achieve the cure (OR 2.34). CONCLUSIONS: Given the long latency of the infection and the risk of developing a severe presentation, screening of S. stercoralis infection should be mandatory in patients coming from or had traveling to endemic areas, especially in those with immunosuppressant conditions.

Osseous cystic echinococcosis: A case series study at a referral unit in Spain.

BACKGROUND: Cystic echinococcosis (CE) is present in all continents, except for the Antarctica. Characteristically, CE lesions are found in the liver and the lungs, but virtually any part of the body may be affected (the spleen, kidneys, heart, central nervous system, bones, among others). It is estimated that the incidence of bone involvement in CE is 0.5% to 4%. METHODOLOGY: A retrospective study was performed of patients with osseous CE treated at the National Reference Unit of Tropical Diseases of the Ramon y Cajal Hospital, Madrid, Spain, between 1989 and December 2017. Epidemiological, clinical, diagnostic and therapeutic data of patients with long-term follow-up were collected. MAIN FINDINGS: During the study period, of the 104 patients with CE, 27 exhibited bone involvement (26%). The bones most frequently affected were the spine, followed by the ribs, pelvis, femur, tibia and the scapula. The most common symptom was pain followed by medullar syndrome and pathologic fracture. In total, 81.5% of patients underwent surgery for osseous CE at least once. As many as 96% received albendazol either in (mostly long-term) monotherapy or in combination with praziquantel. CONCLUSIONS: The diagnosis and management of osseous CE is challenging. In many cases osseous CE should be considered a chronic disease and should be managed on a case-by-case basis. Lifelong follow-up should be performed for potential recurrence and sequels.

Analysis of the costs and cost-effectiveness of the guidelines recommended by the 2018 GESIDA/Spanish National AIDS Plan for initial antiretroviral therapy in HIV-infected adults.

BACKGROUND: The GESIDA/National AIDS Plan expert panel recommended preferred regimens (PR), alternative regimens (AR) and other regimens (OR) for antiretroviral treatment (ART) as initial therapy in HIV-infected patients for 2018. The objective of this study was to evaluate the costs and the efficiency of initiating treatment with PR and AR. METHODS: Economic assessment of costs and efficiency (cost-effectiveness) based on decision tree analyses. Effectiveness was defined as the probability of reporting a viral load <50copies/mL at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen, and drug-resistance studies) over the first 48 weeks. The payer perspective (National Health System) was applied considering only differential direct costs: ART (official prices), management of adverse effects, studies of resistance, and HLA B*5701 testing. The setting was Spain and the costs correspond to those of 2018. A deterministic sensitivity analysis was conducted, building three scenarios for each regimen: base case, most favourable and least favourable. RESULTS: In the base-case scenario, the cost of initiating treatment ranges from 6788 euros for TAF/FTC/RPV (AR) to 10,649 euros for TAF/FTC+RAL (PR). The effectiveness varies from 0.82 for TAF/FTC+DRV/r (AR) to 0.91 for TAF/FTC+DTG (PR). The efficiency, in terms of cost-effectiveness, ranges from 7814 to 12,412 euros per responder at 48 weeks, for ABC/3TC/DTG (PR) and TAF/FTC+RAL (PR), respectively. CONCLUSION: Considering ART official prices, the most efficient regimen was ABC/3TC/DTG (PR), followed by TAF/FTC/RPV (AR) and TAF/FTC/EVG/COBI (AR).

Buruli ulcers in a Spanish aid worker after a stay in Peru.

Buruli ulcer (BU) is a chronic and destructive infection of the skin and soft tissues caused by Mycobacterium ulcerans. Recently, population flows have triggered the appearance of several sporadic cases of BU in non-endemic countries. This represents a significant diagnostic challenge for clinicians and microbiologists. We describe the first case of BU imported to Spain. The patient was a Spanish woman who had stayed 5 months in the jungle of Peru.

Neurocognitive safety after 96 weeks on dual therapy with atazanavir/ritonavir plus lamivudine: results of the neurocognitive substudy of the SALT randomized clinical trial.

Background: Concerns have been voiced over the capacity of deintensification strategies to preserve neurocognitive function and prevent neurocognitive impairment. Methods: We present the 96 week results of a neurocognitive substudy nested within the SALT clinical trial: a randomized, open-label, non-inferiority trial that compares whether atazanavir/ritonavir + lamivudine is non-inferior to atazanavir/ritonavir + two NRTIs in HIV-suppressed patients on stable triple therapy. A global deficit score (GDS) for five neurocognitive tasks was used to assess neurocognitive function. Changes in neurocognitive function (GDS value) were determined at weeks 48 and 96. The effect of atazanavir/ritonavir + lamivudine, adjusted for significant confounders, on the change in neurocognitive function was determined using analysis of covariance (ANCOVA) at week 96. Results: The per-protocol analysis included 92 participants (47 atazanavir/ritonavir + lamivudine and 45 atazanavir/ritonavir + two NRTIs). All baseline characteristics were comparable in both groups. At weeks 48 and 96, changes in GDS [week 48, atazanavir/ritonavir + lamivudine -0.3 (95% CI -0.5 to -0.1) versus atazanavir/ritonavir + two NRTIs -0.2 (95% CI -0.4 to 0.0), P = 0.39; week 96, atazanavir/ritonavir + lamivudine -0.3 (95% CI -0.5 to -0.1) versus atazanavir/ritonavir + two NRTIs -0.2 (95% CI -0.4 to -0.1); P = 0.471] were similar. This absence of differences was also observed in all cognitive tasks. Atazanavir/ritonavir + lamivudine did not impact the change in neurocognitive function at week 96; the adjusted effect of atazanavir/ritonavir + lamivudine on GDS change, considering atazanavir/ritonavir + two NRTIs as a reference, was 0.01 (95% CI -0.18 to 0.21) (P = 0.90). Conclusions: Neurocognitive function remained stable after 96 weeks, both in the atazanavir/ritonavir + lamivudine and in the atazanavir/ritonavir + two NRTIs arms, provided HIV remained suppressed.

Costs and cost-efficacy analysis of the 2017 GESIDA/Spanish National AIDS Plan recommended guidelines for initial antiretroviral therapy in HIV-infected adults.

INTRODUCTION: GESIDA and the Spanish National AIDS Plan panel of experts have recommended preferred (PR), alternative (AR) and other regimens (OR) for antiretroviral therapy (ART) as initial therapy in HIV-infected patients for 2017. The objective of this study was to evaluate the costs and the efficiency of initiating treatment with PR and AR. METHODS: Economic assessment of costs and efficiency (cost-efficacy) based on decision tree analyses. Efficacy was defined as the probability of reporting a viral load <50copies/mL at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen and drug resistance studies) during the first 48 weeks. The payer perspective (National Health System) was applied considering only differential direct costs: ART (official prices), management of adverse effects, resistance studies and HLA B*5701 screening. The setting was Spain and the costs correspond to those of 2017. A deterministic sensitivity analysis was conducted, building three scenarios for each regimen: base case, most favourable and least favourable. RESULTS: In the base case scenario, the cost of initiating treatment ranged from 6882 euro for TFV/FTC/RPV (AR) to 10,904 euros for TFV/FTC+RAL (PR). The efficacy varied from 0.82 for TFV/FTC+DRV/p (AR) to 0.92 for TAF/FTC/EVG/COBI (PR). The efficiency, in terms of cost-efficacy, ranged from 7923 to 12,765 euros per responder at 48 weeks, for ABC/3TC/DTG (PR) and TFV/FTC+RAL (PR), respectively. CONCLUSION: Considering ART official prices, the most efficient regimen was ABC/3TC/DTG (PR), followed by TFV/FTC/RPV (AR) and TAF/FTC/EVG/COBI (PR).

Imported malaria in Spain (2009-2016): results from the +REDIVI Collaborative Network.

BACKGROUND: Imported malaria is a frequent diagnosis in travellers and migrants. The objective of this study was to describe the epidemiological and clinical characteristics of patients diagnosed with imported malaria within a Spanish collaborative network registering imported diseases (+REDIVI). In addition, the possible association between malaria and type of case, gender, age or area of exposure was explored. METHODS: Cases of imported malaria were identified among all cases registered in the +REDIVI database during the period October 2009-October 2016. Demographic, epidemiological and clinical characteristics were analysed. RESULTS: In total, 11,816 cases of imported infectious diseases were registered in +REDIVI's database between October 2009 and October 2016. Immigrants seen for the first time after migration accounted for 60.2% of cases, 21.0% of patients were travellers, and 18.8% were travellers/immigrants visiting friends and relatives (VFRs). There were 850 cases of malaria (850/11,816, 7.2%). Malaria was significantly more frequent in men than in women (56.8% vs 43.2%) and in VFR-immigrants (52.6%) as compared to travellers (21.3%), immigrants (20.7%) and VFR-travellers (5.4%) (p < 0.001). Although this data was not available for most patients with malaria, only a minority (29/217, 13.4%) mentioned correct anti-malarial prophylaxis. Sub-Saharan Africa was found to be the most common region of acquisition of malaria. Most common reason for consultation after travel was a febrile syndrome although an important proportion of immigrants were asymptomatic and presented only for health screening (27.3%). Around 5% of travellers presented with severe malaria. The most prevalent species of Plasmodium diagnosed was Plasmodium falciparum (81.5%). Malaria due to Plasmodium ovale/Plasmodium vivax was frequent among travellers (17%) and nearly 5% of all malaria cases in immigrants were caused by Plasmodium malariae. CONCLUSIONS: Malaria was among the five most frequent diagnoses registered in +REDIVI's database. Some significant differences were found in the distribution of malaria according to gender, type of case, species. Among all malaria cases, the most frequent diagnosis was P. falciparum infection in VFR-immigrant men.

Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. Cruzi Carriers: The STOP-CHAGAS Trial.

BACKGROUND: Benznidazole is recommended for treatment of Chagas infection. Effects of combination therapy with benznidazole and posaconazole have not been tested in Trypanosoma cruzi carriers. OBJECTIVES: The purpose of this study was to determine whether posaconazole alone or combined with benznidazole were superior to benznidazole monotherapy in eliminating T. cruzi parasites measured by real time polymerase chain reaction (RT-PCR) in asymptomatic Chagas carriers. METHODS: A prospective, multicenter randomized placebo-controlled study was conducted in 120 subjects from Latin America and Spain who were randomized to 4 groups: posaconazole 400 mg twice a day (b.i.d.); benznidazole 200 mg + placebo b.i.d.; benznidazole 200 mg b.i.d. + posaconazole 400 mg b.i.d.; or placebo 10 mg b.i.d. T. cruzi deoxyribonucleic acid was detected by RT-PCR at 30, 60, 90, 120, 150, 180, and 360 days. The primary efficacy outcome is the proportion of subjects with persistent negative RT-PCR by day 180; the secondary outcome was negative RT-PCR at 360 days. RESULTS: Only 13.3% of those receiving posaconazole and 10% receiving placebo achieved the primary outcome, compared with 80% receiving benznidazole + posaconazole and 86.7% receiving benznidazole monotherapy (p < 0.0001 vs. posaconazole/placebo). Posaconazole monotherapy or posaconazole combined with benznidazole achieved high RT-PCR conversion rates during treatment (30 days; 93.3% and 88.9% and 60 days; 90%, and 92.3%) that were similar to benznidazole (89.7% and 89.3%); all were superior to placebo or posaconazole (10% and 16.7%, p < 0.0001). This was not observed at 360 days; benznidazole + posaconazole and benznidazole monotherapy (both 96%) versus placebo (17%) and posaconazole (16%, p < 0.0001). Serious adverse events were rare (6 patients) and were observed in the benznidazole-treated patients. Permanent discontinuation was reported in 19 patients (31.7%) receiving either benznidazole monotherapy or combined with posaconazole. CONCLUSIONS: Posaconazole demonstrated trypanostatic activity during treatment, but it is ineffective long-term in asymptomatic T. cruzi carriers. Benznidazole monotherapy is superior to posaconazole, with high RT-PCR conversion rates sustained at 1 year. Side effects lead to therapy discontinuation in 32%. No advantages were observed with combined therapy versus benznidazole monotherapy. (A Study of the Use of Oral Posaconazole [POS] in the Treatment of Asymptomatic Chronic Chagas Disease [P05267] [STOP CHAGAS]: NCT01377480).

HIV, HPV, and microbiota: partners in crime?

Altered interplay between gut mucosa and dysbiotic bacteria during HIV infection seems to fuel chronic immune dysfunction and might explain the excess rates of human papillomavirus (HPV)-associated anal cancer in HIV-infected individuals. Here, we show in HIV-infected MSM undergoing screening for HPV-related cancer that specific fecal and mucosal bacteria are able to predict the existence of precancerous anal lesions. If confirmed, these bacterial biomarkers could be exploited either as diagnostic tools or therapeutic targets.