Intrahost Monkeypox Virus Genome Variation in Patient with Early Infection, Finland, 2022.

Monkeypox virus was imported into Finland during late May-early June 2022. Intrahost viral genome variation in a sample from 1 patient comprised a major variant with 3 lineage B.1.3-specific mutations and a minor variant with ancestral B.1 nucleotides. Results suggest either ongoing APOBEC3 enzyme-mediated evolution or co-infection.

Introduction and Rapid Spread of SARS-CoV-2 Omicron Variant and Dynamics of BA.1 and BA.1.1 Sublineages, Finland, December 2021.

Multiple introductions of SARS-COV-2 Omicron variant BA.1 and BA.1.1. lineages to Finland were detected in early December 2021. Within 3 weeks, Omicron overtook Delta as the most common variant in the capital region. Sequence analysis demonstrated the emergence and spread through community transmission of a large cluster of BA.1.1 virus.

Sindbis virus outbreak and evidence for geographical expansion in Finland, 2021.

Sindbis virus (SINV) caused a large outbreak in Finland in 2021 with 566 laboratory-confirmed human cases and a notable geographical expansion. Compared with the last large outbreak in 2002, incidence was higher in several hospital districts but lower in traditionally endemic locations in eastern parts of the country. A high incidence is also expected in 2022. Awareness of SINV should be raised in Finland to increase recognition of the disease and prevent transmission through the promotion of control measures.

A Combination of N and S Antigens With IgA and IgG Measurement Strengthens the Accuracy of SARS-CoV-2 Serodiagnostics.

BACKGROUND: Primary diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is based on detection of virus RNA in nasopharyngeal swab samples. In addition, analysis of humoral immunity against SARS-CoV-2 has an important role in viral diagnostics and seroprevalence estimates. METHODS: We developed and optimized an enzyme immunoassays (EIA) using SARS-CoV-2 nucleoprotein (N), S1 and receptor binding domain (RBD) of the viral spike protein, and N proteins from SARS, Middle East respiratory syndrome (MERS), and 4 low-pathogenic human CoVs. Neutralizing antibody activity was compared with SARS-CoV-2 IgG, IgA, and IgM EIA results. RESULTS: The sensitivity of EIA for detecting immune response in COVID-19 patients (n = 101) was 77% in the acute phase and 100% in the convalescent phase of SARS-CoV-2 infection when N and RBD were used as antigens in IgG and IgA specific EIAs. SARS-CoV-2 infection significantly increased humoral immune responses against the 229E and NL63 N proteins. S1 and RBD-based EIA results had a strong correlation with microneutralization test results. CONCLUSIONS: The data indicate a combination of SARS-CoV-2 S1 or RBD and N proteins and analysis of IgG and IgA immunoglobulin classes in sera provide an excellent basis for specific and sensitive serological diagnostics of COVID-19.

Incidence Trends for SARS-CoV-2 Alpha and Beta Variants, Finland, Spring 2021.

Severe acute respiratory syndrome coronavirus 2 Alpha and Beta variants became dominant in Finland in spring 2021 but had diminished by summer. We used phylogenetic clustering to identify sources of spreading. We found that outbreaks were mostly seeded by a few introductions, highlighting the importance of surveillance and prevention policies.

Evaluation of commercial and automated SARS-CoV-2 IgG and IgA ELISAs using coronavirus disease (COVID-19) patient samples.

Antibody-screening methods to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) need to be validated. We evaluated SARS-CoV-2 IgG and IgA ELISAs in conjunction with the EUROLabworkstation (Euroimmun, Lübeck, Germany). Overall specificities were 91.9% and 73.0% for IgG and IgA ELISAs, respectively. Of 39 coronavirus disease patients, 13 were IgG and IgA positive and 11 IgA alone at sampling. IgGs and IgAs were respectively detected at a median of 12 and 11 days after symptom onset.

Mycoplasma pneumoniae outbreak, Southeastern Finland, 2017-2018: molecular epidemiology and laboratory diagnostic lessons.

This study characterizes a large Mycoplasma pneumoniae outbreak observed in Kymenlaakso in Southeastern Finland during August 2017-January 2018. The first part of the investigation included 327 patients, who sought healthcare consultation at local GPs or hospitals due to clinical symptoms, and were tested for M. pneumoniae antibodies (Patient cohort). The second part of the investigation, conducted approximately 4 weeks after the peak of the outbreak, consisted of school screening of pupils (N = 239) in three different school buildings by PCR on respiratory specimens and questionnaires (Screening cohort). PCR positive respiratory specimens were subsequently utilized for molecular typing. The outbreak peaked in late October 2017. Of the Patient cohort, 9/106 (8.5%) respiratory specimens were PCR positive. In contrast, 3/182 (1.6%) of the Screening cohort were PCR positive. Asymptomatic carriage was observed. Multiple-locus variable-number tandem-repeat analysis (MLVA) identified two distinct MLVA types. All typed M. pneumoniae strains belonged to P1 type 1. No mutations leading to macrolide resistance were observed. In total, 61/327 (19%) of the Patient cohort had a serological indication of recent infection. The IgM test reactivity at the time of a negative PCR test result varied from a completely non-reactive value up to very strong reactivity, highlighting the difficulty in a single specimen serodiagnosis.

Sindbis virus as a human pathogen-epidemiology, clinical picture and pathogenesis.

Sindbis virus (SINV; family Togaviridae, genus Alphavirus) is an enveloped RNA virus widely distributed in Eurasia, Africa, Oceania and Australia. SINV is transmitted among its natural bird hosts via mosquitoes. Human disease caused by SINV infection has been reported mainly in South Africa and in Northern Europe. Vector mosquito abundance affects the annual incidence of SINV infections with occasional outbreaks of up to 1500 patients. Symptoms include fever, malaise, rash and musculoskeletal pain. In a significant portion of patients the debilitating musculoskeletal symptoms persist for years. Chronic disease after SINV infection shares many features with autoimmune diseases. Currently there is no specific treatment available. Recently SINV infections have been detected outside the previously known distribution range. In this article we will summarize the current knowledge on epidemiology, clinical disease and pathogenesis of SINV infection in man. Copyright © 2016 John Wiley & Sons, Ltd.

Surveillance of endemic foci of tick-borne encephalitis in Finland 1995-2013: evidence of emergence of new foci.

The geographical risk areas for tick-borne encephalitis (TBE) in Finland remained the same until the beginning of the 21st century, but a considerable geographical expansion has been observed in the past 10 years. In order to support public health measures, the present study describes the number of laboratory-confirmed TBE cases and laboratory tests conducted and the associated trends by hospital district, with a particular emphasis on the suspected geographical risk areas. An additional investigation was conducted on 1,957 clinical serum samples throughout the country taken from patients with neurological symptoms to screen for undiagnosed TBE cases. This study identified new TBE foci in Finland, reflecting the spread of the disease into new areas. Even in the most endemic municipalities, transmission of TBE to humans occurred in very specific and often small foci. The number of antibody tests for TBE virus more than doubled (an increase by 105%) between 2007 and 2013. Analysis of the number of tests also revealed areas in which the awareness of clinicians may be suboptimal at present. However, it appears that underdiagnosis of neuroinvasive TBE is not common.

Prolonged myalgia in Sindbis virus infection: case description and in vitro infection of myotubes and myoblasts.

BACKGROUND: Sindbis virus (SINV) is a mosquito-borne alphavirus found in Eurasia, Africa, and Oceania. Clinical SINV infection is characterized by febrile rash and arthritis and sometimes prolonged arthralgia and myalgia. The pathophysiological mechanisms of musculoskeletal and rheumatic disease caused by SINV are inadequately understood. METHODS: We studied the muscle pathology of SINV infection ex vivo by examining a unique muscle biopsy obtained from a patient with chronic myalgia and arthralgia 6 months after acute SINV infection and assessed potential genetic predisposing factors by determining the human leukocyte antigen (HLA) and complement factor C4 genes and proteins. In addition, we performed in vitro SINV infections of primary human myoblasts and myotubes. RESULTS: In the muscle biopsy we found evidence of muscle regeneration due to previous necrotic lesions likely caused by earlier SINV infection. We showed that human myoblasts and myotubes were susceptible in vitro for SINV infection as the cells became immunoreactive for viral antigens and cytopathic effect was observed. The patient was homozygous for HLA-B*35 alleles and heterozygous for HLA-DRB1*01 and HLA-DRB1*03 alleles and had total deficiency of C4B protein. CONCLUSIONS: This study provides new insights concerning pathological processes leading to chronic symptoms in SINV infection and demonstrates for the first time the susceptibility of human myogenic cells to SINV infection.

Clinical Sindbis alphavirus infection is associated with HLA-DRB1*01 allele and production of autoantibodies.

BACKGROUND: Sindbis virus (SINV) is a mosquito-borne alphavirus found in Eurasia, Africa, and Oceania. Clinical SINV infection, characterized by arthropathic disease that may persist for years, is primarily reported in Northern Europe where the disease has considerable public health importance in endemic areas. The aim of this study was to investigate the role of genetic factors in the susceptibility and outcome of SINV infection and to elucidate the association between SINV infection and autoimmunity. METHODS: The study included 49 patients with serologically confirmed symptomatic SINV infection who were followed for 3 years after acute infection. Human leukocyte antigen (HLA) genes known to be associated with rheumatic and infectious diseases and complement C4 genes were determined in 35 patients. Furthermore, a set of autoantibodies was measured at the acute phase and 3 years after infection in 44 patients. RESULTS: The frequency of DRB1*01 was significantly higher among patients with SINV infection than in the reference population (odds ratio, 3.3; 95% confidence interval, 1.7-6.5; P = .003). The DRB1*01 allele was particularly frequent in patients who at 3 years postinfection experienced joint manifestations. The frequency of rheumatoid factor at 3 years postinfection was 29.5% and had increased significantly (P = .02) during the 3-year period. In addition, antinuclear and antimitochondrial antibodies were present in serum 3 years postinfection with frequencies of 15.9% and 6.8%, respectively. CONCLUSIONS: Our data show that symptomatic SINV infection is associated with the HLA system and that autoantibody titers are elevated in patients 3 years postinfection. These findings indicate that SINV-induced arthritis shares features with autoimmune diseases.

Robust reconstruction and analysis of outbreak data: influenza A(H1N1)v transmission in a school-based population.

The rapid spread of the new influenza virus A(H1N1)v in young age groups in 2009 has been partly attributed to a high transmission intensity in schools. However, detailed characterization of the spread of influenza in school populations has been difficult to obtain, simply because it is very hard to identify who infected whom in a large outbreak. Data collected in large outbreak investigations typically miss many transmission events, and some reported transmission events will be incorrect. Here the authors present robust likelihood-based methods that can be used to analyze outbreak data while explicitly accounting for both missing data and erroneous data. They apply this method to a school-based outbreak of pandemic influenza A(H1N1)v that occurred in London, United Kingdom, in April 2009. The authors show that the generation interval in this school-based population was 2.20 days and that the reproduction number declined coincident with school closure, from 1.33 secondary cases per primary case to 0.43 secondary cases per primary case. These results provide quantitative evidence for the change in influenza transmission that is to be expected from school closure.

Complete coding sequence and molecular epidemiological analysis of Sindbis virus isolates from mosquitoes and humans, Finland.

Sindbis virus (SINV) is an arthropod-borne alphavirus, which causes rash-arthritis, particularly in Finland. SINV is transmitted by mosquitoes in Finland but thus far no virus has been isolated from mosquitoes. In this study, we report the isolation of the first SINV strain from mosquitoes in Finland and its full-length protein-coding sequence. We furthermore describe the full-length coding sequence of six SINV strains previously isolated from humans in Finland and from a mosquito in Russia. The strain isolated from mosquitoes (Ilomantsi-2005M) was very closely related to all the other Northern European SINV strains. We found 9 aa positions, of which five in the nsP3 protein C terminus, to be distinctive signatures for the Northern European strains that may be associated with vector or host species adaptation. Phylogenetic analyses further indicate that SINV has a local circulation in endemic regions in Northern Europe and no novel strains are frequently being introduced.

Epidemic sindbis virus infection in Finland: a population-based case-control study of risk factors.

BACKGROUND: Sindbis virus (SINV) is an arthropod-borne alphavirus that causes rash and arthritis. In Finland, epidemics occur cyclically, but factors associated with clinical SINV infection are largely unknown. We conducted a population-based case-control study during the epidemic year 2002. METHODS: SINV cases were serologically confirmed and reported to the National Infectious Disease Registry. Five control subjects, matched for age, sex, and residence, were selected from the National Population Information System. Data were collected using a self-administered mail survey. Conditional logistic regression models were used to identify independent risk factors; missing data were addressed using Bayesian full-likelihood modeling. RESULTS: A total of 337 case patients (58% female; age range, 1-94 y) and 934 control subjects were enrolled. Reported exposure to mosquito bites (matched odds ratio [mOR], 16.7; 95% confidence interval [CI], 9.1-33.4) and spending time in woods or marshland (mOR, 1.8; 95% CI, 1.3-2.5) were independently associated with SINV infection in the multivariable model. The population-attributable risk for mosquito bites was 87.2%. There were dose-response relations for increased number of insect bites (mOR, 23.8-72.5) and increased time spent in woods or marshland (mOR, 1.3-2.2). CONCLUSIONS: Educating the public in endemic areas to avoid mosquito exposure and use protective measures remain important prevention measures for SINV infection.

Comparative evaluation of four commercial analyzers for the serological screening of hepatitis A, B, C and HIV.

BACKGROUND: Independent evaluations that deploy clinical patient samples are important in assessing the performance of commercial tests used for serological screening of viral hepatitis and HIV in clinical laboratories. OBJECTIVES: We compared the analytical performance of Abbott Architect i2000SR, Abbott Alinity i, DiaSorin Liaison XL, and Siemens Atellica for the following analytes: anti-HAV IgG/anti-HAV total, anti-HAV IgM, HBsAg, anti-HBc IgM, Anti-HBc, HBeAg, anti-HBe, anti-HBs, anti-HCV, and HIV Ag/Ab. In addition, anti-HBc IgM, HBeAg, and anti-HBe were evaluated for Abbott Architect, Abbott Alinity and DiaSorin Liaison. STUDY DESIGN: Pseudonymized clinical serum specimens (N = 98-200 for each analyte) were selected for the analysis according to their reactivity on the Abbott Architect. The results were compared against Abbott Architect and against consensus. RESULTS: A generally high agreement was observed between the tests. Abbott Alinity had the lowest anti-HAV IgG/total specificity (75.9% against Abbott Architect and 83.0% against consensus). The comparatively low sensitivity of Siemens Atellica (78.2%), Abbott Alinity (87.5%) and DiaSorin Liaison (89.3%) for anti-HAV IgM against Abbott Architect may reflect a higher false-positive rate of Abbott Architect. Particular variation was observed in the sensitivity values of anti-HBc, HBsAg and HIV Ag/Ab between the test methods. DiaSorin Liaison anti-HBs gave consistently higher values as compared to the other tests. CONCLUSIONS: The serodiagnostic methods for HIV and viral hepatitis of Abbott Architect, Abbott Alinity, DiaSorin Liaison, and Siemens Atellica performed well in comparison with each other. The observed differences between the tests will provide useful information for clinical laboratories in planning their workflows for screening and confirmation.

Consumption of healthcare services and antibiotics in patients with presumed disseminated Lyme borreliosis before and after evaluation of an infectious disease specialist.

Our objective was to study the consumption of healthcare services and antibiotics in patients with suspicion of disseminated Lyme borreliosis (LB) before and after consultation of an infectious disease specialist. We evaluated retrospectively all presumed disseminated LB patients (n = 256) with a referral to the Department of Infectious Diseases (DID) in Helsinki University Hospital in 2013. Medical records from all healthcare providers in the area were reviewed and the number of physician contacts because of symptoms leading to LB suspicion and antimicrobial purchases were calculated 1 year before and after consultation or treatment at the DID. Patients were divided into three groups according to certainty of LB: unlikely, possible or probable/definite LB. The number of healthcare contacts 1 year before referral was higher among 121 patients with unlikely LB (6; interquartile range [IQR] 3-10), than 65 possible (4; IQR 2.5-7; p = 0.018) or 66 probable/definite LB patients (4; IQR 2.8-7; p = 0.010). The median number of contacts to healthcare during one year after consultation or treatment was 3 (IQR 0.5-7), 1 (IQR 0-3) and 0.5 (IQR 0-2.3), respectively, with a statistically significant difference between the groups (p<0.001). Antibiotics were purchased by 151 (60%) patients one year before referral and by 127 (50%) patients year after consultation or treatment at DID without statistically significant difference between groups with different LB certainty. These antibiotic purchases do not include the treatments prescribed by infectious disease specialists. In the case of 27 patients, an antimicrobial treatment was recommended in the consultation reply. In conclusion, patients with unlikely LB used more healthcare services than patients with possible or probable/definite LB. Antimicrobial consumption was similar between groups of different LB certainty.

The phylodynamics of SARS-CoV-2 during 2020 in Finland.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of infections and fatalities globally since its emergence in late 2019. The virus was first detected in Finland in January 2020, after which it rapidly spread among the populace in spring. However, compared to other European nations, Finland has had a low incidence of SARS-CoV-2. To gain insight into the origins and turnover of SARS-CoV-2 lineages circulating in Finland in 2020, we investigated the phylogeographic and -dynamic history of the virus. Methods: The origins of SARS-CoV-2 introductions were inferred via Travel-aware Bayesian time-measured phylogeographic analyses. Sequences for the analyses included virus genomes belonging to the B.1 lineage and with the D614G mutation from countries of likely origin, which were determined utilizing Google mobility data. We collected all available sequences from spring and fall peaks to study lineage dynamics. Results: We observed rapid turnover among Finnish lineages during this period. Clade 20C became the most prevalent among sequenced cases and was replaced by other strains in fall 2020. Bayesian phylogeographic reconstructions suggested 42 independent introductions into Finland during spring 2020, mainly from Italy, Austria, and Spain. Conclusions: A single introduction from Spain might have seeded one-third of cases in Finland during spring in 2020. The investigations of the original introductions of SARS-CoV-2 to Finland during the early stages of the pandemic and of the subsequent lineage dynamics could be utilized to assess the role of transboundary movements and the effects of early intervention and public health measures.

[Chikungunya, a new global epidemic?]. / Chikungunya, uusi maailmanlaajuinen epidemia?

Chikungunya virus, originating from Africa, hit the headlines in 2004 upon causing a large-scale epidemic. Typical symptoms of chikungunya virus infection include severe joint aches, high fever and skin rash. Increased incidence of neurologic symptoms was noted in connection with the epidemic of the recent years, and deaths were also reported. A single point mutation in the viral genome enabled an effective multiplication of the virus in a species of mosquito (Aedes albopictus) that was new to the virus. During the last decades, this species of mosquito has spread into Southern Europe, and the spreading is likely to continue.