Evaluation of the accuracy of a multi-infection screening test based on a multiplex immunoassay targeting imported diseases common in migrant populations.

BACKGROUND: We aimed to evaluate the performance of a novel multiplex serological assay, able to simultaneously detect IgG of six infections, as a screening tool for imported diseases in migrants. METHODS: Six panels of 40 (n = 240) anonymized serum samples with confirmed infections were used as positive controls to assess the multiplex assay's sensitivity. One panel of 40 sera from non-infected subjects was used to estimate the seropositivity cutoffs, and 32 non-infected sera were used as negative controls to estimate each serology's sensitivity and specificity. The multi-infection screening test was validated in a prospective cohort of 48 migrants from endemic areas. The sensitivity of the Luminex assay was calculated as the proportion of positive results over all positive samples identified by reference tests. The specificity was calculated using 32 negative samples. Uncertainty was quantified with 95 % confidence intervals using receiver operating characteristic analyses. RESULTS: The sensitivity/specificity were 100 %/100 % for HIV (gp41 antigen), 97.5 %/100 % for Hepatitis B virus (HBV-core antigen), 100 %/100 % for Hepatitis C virus (HCV-core antigen), 92.5 %/90.6 % for strongyloidiasis [31-kDa recombinant antigen (NIE)], 97.5 %/100 % for schistosomiasis (combined serpin Schistosoma mansoni and S.haematobium antigens) and 95 %/90.6 % for Chagas disease [combined Trypanosoma cruzi kinetoplastid membrane protein-11 (KMP11) and paraflagellar rod proteins 2 (PFR2) antigens]. In the migrant cohort, antibody response to the combination of the T.cruzi antigens correctly identified 100 % individuals, whereas HBV-core antigen correctly identified 91.7 % and Strongyloides-NIE antigen 86.4 %. CONCLUSIONS: We developed a new, robust and accurate 8-plex Luminex assay that could facilitate the implementation of screening programmes targeting migrant populations.

Screening and routine diagnosis of mental disorders among migrants in primary care: A cross-sectional study.

Background: Migrants in host countries are at risk for the development of mental health conditions. The two aims of the study were to describe routine diagnoses of mental disorders among migrant patients at primary healthcare level and the associated risk factors, and to test the utility of an innovative migrant mental health assessment by evaluating whether the health professionals followed the recommendations proposed by the clinical decision support system (CDSS) tool. Methods: A cross-sectional study was carried out in eight primary care centres (PCCs) in four non-randomly selected health regions of Catalonia, Spain from March to December 2018. Routine health data and mental health diagnoses based on the International Classification of Diseases (10th edition), including mental, behavioural and neuro developmental disorders (F01-F99), symptoms and signs involving emotional state (R45), and sleep disorders (G47), were extracted from the electronic health records. The proportion of mental health conditions was estimated and logistic regression models were used to assess any possible association with mental health disorders. The utility of the mental health assessment was assessed with the proportion of questionnaires performed by health professionals for migrants fulfilling the mental health screening criterion (country of origin with an active conflict in 2017) and the diagnoses given to the screened patients. Results: Of 14,130 migrants that visited any of the PCCs during the study period, 7,358 (52.1 %) were women with a median age of 38.0 years-old. There were 520/14,130 (3.7 %) migrant patients diagnosed with a mental disorder, being more frequent among women (342/7,358; 4.7 %, p-value < 0.001), migrants from Latin-America (177/3,483; 5.1 %, p < 0.001) and those who recently arrived in Spain (170/3,672; 4.6 %, p < 0.001). A lower proportion of mental disorders were reported in migrants coming from conflicted countries in 2017 (116/3,669, 3.2 %, p = 0.053).Out of the 547 mental health diagnoses reported in 520 patients, 69/14,130 (0.5 %) were mood disorders, 346/14,130 (2.5 %) anxiety disorders and 127/14,130 (0.9 %) sleeping disorders. Mood disorders were more common in migrants from Eastern Europe (25/2,971; 0.8 %, p < 0.001) and anxiety disorders in migrants from Latin-America (126/3,483; 3.6 %, p < 0.001), while both type of disorders were more often reported in women (p < 0.001).In the adjusted model, women (aOR: 1.5, [95 % CI 1.2-1.8, p < 0.001]), migrants with more than one visit to the health center during the study period (aOR: 4.4, [95 %CI 2.8-6.8, p < 0.001]) and who presented an infectious disease (aOR: 2.1, [95 %CI 1.5-3.1, p < 0.001]) had higher odds of having a mental disorder.Lastly, out of the 1,840 migrants coming from a conflicted country in 2017 who were attended in centres where the CDSS tool was implemented, 29 (1.6 %) had a mental health assessment performed and the tool correctly identified one individual. Conclusions: Mental health is a condition that may be overlooked in migrants at primary healthcare. Interventions at this level of care must be reinforced and adapted to the needs and circumstances of migrants to ensure equity in health services.

Clinical evaluation of BioFire® multiplex-PCR panel for acute undifferentiated febrile illnesses in travellers: a prospective multicentre study.

BACKGROUND: Identifying the causes of Acute Undifferentiated Febrile Illness (AUFI) is key to improve the management of returning travellers with fever. We evaluated a BioFire®FilmArray® prototype panel of multiplex nucleic acid amplification tests (NAAT) targeting different relevant pathogens in travellers returning with fever. METHODS: Prospective, multicentre study to evaluate a prototype panel in whole blood samples of adult international travellers presenting with AUFI in three European travel Clinics/Hospitals (November 2017-November 2019). We evaluated 15 target analytes: Plasmodium spp., Plasmodium falciparum, Plasmodium knowlesi, Plasmodium malariae, Plasmodium ovale, Plasmodium vivax, chikungunya virus, dengue virus, Zika virus, Anaplasma phagocytophilum, Borrelia spp., Leptospira spp., Orientia tsutsugamushi, Rickettsia spp. and Salmonella spp. Results were compared with composite reference standards (CRSs) for each target infection, including direct methods [smear microscopy, rapid diagnostic test (RDT), reference NAAT and blood cultures] and indirect methods (paired serology). FINDINGS: Among 455 travellers with AUFI, 229 target infections were diagnosed; the prototype panel detected 143 (overall sensitivity and specificity of 62.5 and 99.8%, respectively). The panel identified all Plasmodium infections (n = 82). Sensitivity for dengue (n = 71) was 92.9, 80.8 and 68.5% compared with RDT, NAAT and CRS, respectively. Compared with direct methods and CRS, respectively, the prototype panel detected 4/4 and 4/6 chikungunya, 2/2 and 4/29 Leptospira spp., 1/1 and 1/6 O. tsutsugamushi and 2/2 and 2/55 Rickettsia spp., but 0/2 and 0/10 Zika, 0/1 and 0/11 A. phagocytophylum and 0/3 Borrelia spp. diagnosed by serology and only 1/7 Salmonella spp. diagnosed by blood cultures. 77/86 (89.5%) infections not detected by the panel were diagnosed by serology. INTERPRETATION: The prototype panel allowed rapid and reliable diagnosis for malaria, dengue and chikungunya. Further improvements are needed to improve its sensitivity for Zika and important travel-related bacterial infections.

Usefulness and practicality of a multidisease screening programme targeting migrant patients in primary care in Spain: a qualitative study of general practitioners.

OBJECTIVES: Some migrant groups are disproportionately affected by key infectious diseases in European countries. These pose a challenge for healthcare systems providing care to these groups. We aimed to explore the views of general practitioners (GPs) on the acceptability, adaptability and feasibility of a multidisease screening programme based on an innovative clinical decision-support system for migrants (the ISMiHealth tool), by examining the current gaps in healthcare provision and areas of good practice and the usefulness and limitations of training in the health needs of migrants. METHODS: We undertook a qualitative descriptive study and carried out a series of focus groups (FGs) taking a pragmatic utilitarian approach. Participants were GPs from the four primary healthcare (PHC) centres in Catalonia, Spain, that piloted an intervention of the ISMiHealth tool. GPs were recruited using purposive and convenience sampling. FG discussions were transcribed and analysed using thematic content analysis. RESULTS: A total of 29 GPs participated in four FGs. Key themes identified were: (1) GPs found the ISMiHealth tool to be very useful for helping to identify specific health problems in migrants, although there are several additional barriers to screening as part of PHC, (2) the importance of considering cultural perspectives when caring for migrants, and of the impact of migration on mental health, (3) the important role of PHC in healthcare provision for migrants and (4) key proposals to improve screening of migrant populations. GPs also highlighted the urgent need, to shift to a more holistic and adequately resourced approach to healthcare in PHC. CONCLUSIONS: GPs supported a multidisease screening programme for migrant populations using the ISMiHealth tool, which aided clinical decision-making. However, intercultural participatory approaches will need to be adopted to address linguistic and cultural barriers to healthcare access that exist in migrant communities.

Improving the detection of infectious diseases in at-risk migrants with an innovative integrated multi-infection screening digital decision support tool (IS-MiHealth) in primary care: a pilot cluster-randomized-controlled trial.

BACKGROUND: There are major shortfalls in the identification and screening of at-risk migrant groups. This study aims to evaluate the effectiveness of a new digital tool (IS-MiHealth) integrated into the electronic patient record system of primary care centres in detecting prevalent migrant infections. IS-MiHealth provides targeted recommendations to health professionals for screening multiple infections, including human immunodeficiency virus (HIV), hepatitis B and C, active tuberculosis (TB), Chagas disease, strongyloidiasis and schistosomiasis, based on patient characteristics (including variables of country of origin, age and sex). METHODS: A pragmatic pilot cluster-randomized-controlled trial was deployed from March to December 2018. Eight primary care centres in Catalonia, Spain, were randomly allocated 1:1 to use of the digital tool for screening, or to routine care. The primary outcome was the monthly diagnostic yield of all aggregated infections. Intervention and control sites were compared before and after implementation with respect to their monthly diagnostic yield using regression models. This study is registered on international standard randomised controlled trial number (ISRCTN) (ISRCTN14795012). RESULTS: A total of 15 780 migrants registered across the eight centres had at least one visit during the intervention period (March-December 2018), of which 14 598 (92.51%) fulfilled the criteria to be screened for at least one infection. There were 210 (2.57%) individuals from the intervention group with new diagnoses compared with 113 (1.49%) from the control group [odds ratio: 2.08, 95% confidence interval (CI) 1.63-2.64, P < 0.001]. The intervention centres raised their overall monthly diagnosis rate to 5.80 (95% CI 1.23-10.38, P = 0.013) extra diagnoses compared with the control centres. This monthly increase in diagnosis in intervention centres was also observed if we consider all cases together of HIV, hepatitis B and C, and active TB cases [2.72 (95% CI 0.43-5.00); P = 0.02] and was observed as well for the parasitic infections' group (Chagas disease, strongyloidiasis and schistosomiasis) 2.58 (95% CI 1.60-3.57; P < 0.001). CONCLUSIONS: The IS-MiHealth increased screening rate and diagnostic yield for key infections in migrants in a population-based primary care setting. Further testing and development of this new tool is warranted in larger trials and in other countries.

Seven-month kinetics of SARS-CoV-2 antibodies and role of pre-existing antibodies to human coronaviruses.

Unraveling the long-term kinetics of antibodies to SARS-CoV-2 and the individual characteristics influencing it, including the impact of pre-existing antibodies to human coronaviruses causing common cold (HCoVs), is essential to understand protective immunity to COVID-19 and devise effective surveillance strategies. IgM, IgA and IgG levels against six SARS-CoV-2 antigens and the nucleocapsid antigen of the four HCoV (229E, NL63, OC43 and HKU1) were quantified by Luminex, and antibody neutralization capacity was assessed by flow cytometry, in a cohort of health care workers followed up to 7 months (N = 578). Seroprevalence increases over time from 13.5% (month 0) and 15.6% (month 1) to 16.4% (month 6). Levels of antibodies, including those with neutralizing capacity, are stable over time, except IgG to nucleocapsid antigen and IgM levels that wane. After the peak response, anti-spike antibody levels increase from ~150 days post-symptom onset in all individuals (73% for IgG), in the absence of any evidence of re-exposure. IgG and IgA to HCoV are significantly higher in asymptomatic than symptomatic seropositive individuals. Thus, pre-existing cross-reactive HCoVs antibodies could have a protective effect against SARS-CoV-2 infection and COVID-19 disease.

SARS-CoV-2 Seroprevalence and Antibody Kinetics Among Health Care Workers in a Spanish Hospital After 3 Months of Follow-up.

BACKGROUND: At the COVID-19 spring 2020 pandemic peak in Spain, prevalence of SARS-CoV-2 infection in a cohort of 578 randomly selected health care workers (HCWs) from Hospital Clínic de Barcelona was 11.2%. METHODS: A follow-up survey 1 month later (April-May 2020) measured infection by rRT-PCR and IgM, IgA, and IgG to the receptor-binding domain of the spike protein by Luminex. Antibody kinetics, including IgG subclasses, was assessed until month 3. RESULTS: At month 1, the prevalence of infection measured by rRT-PCR and serology was 14.9% (84/565) and seroprevalence 14.5% (82/565). We found 25 (5%) new infections in 501 participants without previous evidence of infection. IgM, IgG, and IgA levels declined in 3 months (antibody decay rates 0.15 [95% CI, .11-.19], 0.66 [95% CI, .54-.82], and 0.12 [95% CI, .09-.16], respectively), and 68.33% of HCWs had seroreverted for IgM, 3.08% for IgG, and 24.29% for IgA. The most frequent subclass responses were IgG1 (highest levels) and IgG2, followed by IgG3, and only IgA1 but no IgA2 was detected. CONCLUSIONS: Continuous and improved surveillance of SARS-CoV-2 infections in HCWs remains critical, particularly in high-risk groups. The observed fast decay of IgA and IgM levels has implications for seroprevalence studies using these isotypes.

Seroprevalence of antibodies against SARS-CoV-2 among health care workers in a large Spanish reference hospital.

Health care workers (HCW) are a high-risk population to acquire SARS-CoV-2 infection from patients or other fellow HCW. This study aims at estimating the seroprevalence against SARS-CoV-2 in a random sample of HCW from a large hospital in Spain. Of the 578 participants recruited from 28 March to 9 April 2020, 54 (9.3%, 95% CI: 7.1-12.0) were seropositive for IgM and/or IgG and/or IgA against SARS-CoV-2. The cumulative prevalence of SARS-CoV-2 infection (presence of antibodies or past or current positive rRT-PCR) was 11.2% (65/578, 95% CI: 8.8-14.1). Among those with evidence of past or current infection, 40.0% (26/65) had not been previously diagnosed with COVID-19. Here we report a relatively low seroprevalence of antibodies among HCW at the peak of the COVID-19 epidemic in Spain. A large proportion of HCW with past or present infection had not been previously diagnosed with COVID-19, which calls for active periodic rRT-PCR testing in hospital settings.