Tuberculosis in immigrants in Finland, 1995-2013.

Increasing immigration from high tuberculosis (TB) incidence countries is a challenge for surveillance and control in Finland. Here, we describe the epidemiology of TB in immigrants by using national surveillance data. During 1995-2013, 7030 (84·7%) native and 1199 (14·4%) immigrant cases were identified. The proportion of immigrant cases increased from 5·8% in 1995 to 32·1% in 2013, consistent with increasing immigrant population (2·1-5·6%) and decreasing incidence of TB in the native population (from 12·1 to 3·5/100 000). TB cases in immigrants were significantly younger, more often female, and had extrapulmonary TB more often than native cases (P < 0·01 for all comparisons); multidrug resistance was also more common in immigrants than natives (P < 0·01). Immigrant cases were born in 82 different countries; most commonly in Somalia and the former Soviet Union/Russia. During 2008-2013, 433 Mycobacterium tuberculosis isolates from immigrants were submitted for spoligotyping; 10 different clades were identified. Clades were similar to those found in the case's country of birth. Screening immigrants from high-incidence countries and raising awareness of common characteristics and symptoms of TB is important to ensure early diagnosis and to prevent transmission.

Evaluation of two commercially available rapid diagnostic tests for Lyme borreliosis.

The diagnosis of Lyme disease is very complicated and a single diagnostic method cannot exclude infection. We assessed the performance of two commercially available Borrelia burgdorferi rapid diagnostic tests (RDT) in comparison to multiple laboratory-based diagnostic assays using specimens with a gradually increasing probability of Borrelia infection. Based on 200 specimens, the analytical sensitivities for IgG and IgM were 18 and 23% for the Lyme RDT and 24 and 32% for the Borreliose Complete RDT. The sensitivity for detecting diagnosed Lyme borreliosis cases was low (26% Lyme RDT and 32% with the Borreliose Complete RDT respectively), whereas the specificity was good (85% Lyme RDT and 88% Borreliose Complete). Based on this evaluation, the performance of RDTs in detecting Lyme borreliosis appeared to be below that of laboratory-based diagnostics.

Epidemiology and emm types of invasive group A streptococcal infections in Finland, 2008-2013.

Invasive Streptococcus pyogenes (group A streptococcus, GAS) infections are a major global cause of morbidity and mortality. We analysed the surveillance data on invasive GAS and the microbiological characteristics of corresponding isolates to assess the incidence and emm type distribution of invasive GAS infections in Finland. Cases defined as patients with isolations of blood and cerebrospinal fluid S. pyogenes are mandatorily notified to the National Infectious Disease Registry and sent to the national reference laboratory for emm typing. Antimicrobial data were collected through the network including all clinical microbiology laboratories. Pulsed-field gel electrophoresis (PFGE) analysis was performed to assess clonality. In total, 1165 cases of invasive GAS were reported in Finland during 2008-2013; the median age was 52 years (range, 0-100) and 54% were male. The overall day 7 case fatality rate was 5.1% (59 cases). The average annual incidence was 3.6 cases per 100,000 population. A total of 1122 invasive GAS isolates (96%) were analysed by emm typing; 72 different emm types were identified, of which emm28 (297 isolates, 26%), emm89 (193 isolates, 12%) and emm1 (132 isolates, 12%) were the most common types. During 2008-2013, an increase of erythromycin resistance (1.9% to 8.7%) and clindamycin (0.9% to 9.2%) was observed. This resistance increase was in parallel with the introduction of a novel clone emm33 into Finland. The overall incidence of invasive GAS infections remained stable over the study period in Finland. We identified clonal spread of macrolide-resistant invasive emm33 GAS type, highlighting the importance of molecular surveillance.

Validation of the clinical performance and reproducibility of the NeuMoDx HPV assay self-sample workflow.

BACKGROUND: Human papillomavirus (HPV) testing on self-samples is a valid tool for cervical cancer screening. HPV self-sample workflows need to be clinically validated to ensure safe use in screening. OBJECTIVE: This study evaluated the fully automated NeuMoDx HPV Assay self-sample workflow that is compiled of the NeuMoDx HPV assay and the NeuMoDx 96/288 Molecular Systems, for clinical performance and reproducibility on Evalyn Brush-collected self-samples. METHODS: The clinical performance of the NeuMoDx HPV Assay self-sample workflow for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3+ was evaluated on 987 self-samples obtained from women attending national organized HPV-based cervical cancer screening by a noninferiority analysis relative to reference workflows using either HPV-Risk Assay or high-risk HPV GP5+/6+-PCR. Intra- and inter-laboratory reproducibility of the NeuMoDx HPV Assay self-sample workflow using both NeuMoDx 96 and 288 Molecular Systems was assessed on 520 self-samples in three laboratories. RESULTS: The clinical sensitivity and specificity of the NeuMoDx HPV Assay self-sample workflow for the detection of CIN2+ and CIN3+ were found to be non-inferior to the reference workflows using either HPV-Risk Assay or high-risk HPV GP5+/6+-PCR, with all p-values <0.034. The NeuMoDx HPV Assay self-sample workflow exhibited an intra-laboratory reproducibility of 94.4 % (95 %CI:92.5-96.1 %) with kappa value 0.86 (95 %CI:0.81-0.91). Inter-laboratory agreement was high (all ≥93.4 % and all kappa values ≥0.83). CONCLUSIONS: The NeuMoDx HPV Assay self-sample workflow demonstrated high clinical accuracy for CIN2+/3+ and high reproducibility. The NeuMoDx HPV Assay self-sample workflow can be considered suitable for cervical cancer screening purposes.

SARS-CoV-2 transmission among health care workers, an outbreak investigation using whole-genome sequencing.

BACKGROUND: We report an outbreak investigation to map intra-hospital transmission among health care workers (HCW) using epidemiological and whole-genome sequencing data. METHODS: Fourteen clinical wards (COVID-19 and non-COVID-19) with high infection rates of SARS-CoV-2 among HCW were selected and demographical, epidemiological and sequencing data were collected of all HCW testing positive by RT-PCR. Clustered cases were identified based on first disease onsets and differences in single nucleotide polymorphisms (SNP's) and were analysed for additional characteristics. RESULTS: Data was collected for 123 HCW. Out of 123 HCW, 65 (53%) worked at eight non-COVID-19 wards, 56 (46%) at four COVID-19 wards, one (<1%) worked on several wards and for one (<1%) it was unknown. One major cluster (n = 34) and three minor clusters (n = 2,3,4; total n = 9) comprising of 43 HCW (35%) were found after comparing our study population (n = 123) with the circulating regional sequences (n = 819). In clustered cases work was most often the suspected source of infection and continuing work while having symptoms occurred in all clusters, ranging from 1-6 days. CONCLUSION: Our findings strongly indicate transmission of SARS-CoV-2 among HCW. Whole-genome sequencing is useful for identification of clusters and can give direction to targeted infection prevention measures.

Evaluation of whole genome sequencing and software tools for drug susceptibility testing of Mycobacterium tuberculosis.

OBJECTIVES: Culture-based assays are currently the reference standard for drug susceptibility testing for Mycobacterium tuberculosis. They provide good sensitivity and specificity but are time consuming. The objective of this study was to evaluate whether whole genome sequencing (WGS), combined with software tools for data analysis, can replace routine culture-based assays for drug susceptibility testing of M. tuberculosis. METHODS: M. tuberculosis cultures sent to the Finnish mycobacterial reference laboratory in 2014 (n = 211) were phenotypically tested by Mycobacteria Growth Indicator Tube (MGIT) for first-line drug susceptibilities. WGS was performed for all isolates using the Illumina MiSeq system, and data were analysed using five software tools (PhyResSE, Mykrobe Predictor, TB Profiler, TGS-TB and KvarQ). Diagnostic time and reagent costs were estimated for both methods. RESULTS: The sensitivity of the five software tools to predict any resistance among strains was almost identical, ranging from 74% to 80%, and specificity was more than 95% for all software tools except for TGS-TB. The sensitivity and specificity to predict resistance to individual drugs varied considerably among the software tools. Reagent costs for MGIT and WGS were €26 and €143 per isolate respectively. Turnaround time for MGIT was 19 days (range 10-50 days) for first-line drugs, and turnaround time for WGS was estimated to be 5 days (range 3-7 days). CONCLUSIONS: WGS could be used as a prescreening assay for drug susceptibility testing with confirmation of resistant strains by MGIT. The functionality and ease of use of the software tools need to be improved.

Whole genome analysis of Mycobacterium tuberculosis isolates from recurrent episodes of tuberculosis, Finland, 1995-2013.

Recurrent tuberculosis (TB) is caused by an endogenous re-activation of the same strain of Mycobacterium tuberculosis (relapse) or exogenous infection with a new strain (re-infection). Recurrence of TB in Finland was analysed in a population-based, 19-year study, and genotyping was used to define relapse and re-infection. The M. tuberculosis isolates from patients with suspected relapse were further analysed by whole genome sequencing (WGS) to determine the number and type of mutations occurring in the bacterial genome between the first and second disease episodes. In addition, publicly available tools (PhyResSE and SpolPred) were used to predict drug resistance and spoligotype profile from the WGS data. Of the 8299 notified TB cases, 48 (0.6%) patients had episodes classified as recurrent. Forty-two patients had more than one culture-confirmed TB episode, and isolates from two episodes in 21 patients were available for genotyping. In 18 patients, the M. tuberculosis isolates obtained from the first and second TB episodes had identical spoligotypes. The WGS analysis of the 36 M. tuberculosis isolates from the 18 suspected relapse patients (average time between isolates 2.8 years) revealed 0 to 38 single nucleotide polymorphisms (median 1, mean 3.78) between the first and second isolate. There seemed to be no direct relation between the number of years between the two isolates, or treatment outcome, and the number of single nucleotide polymorphisms. The results suggest that the mutation rate may depend on multiple host-, strain- and treatment-related factors.

Genotypic characterization and historical perspective of Mycobacterium tuberculosis among older and younger Finns, 2008-2011.

The Mycobacterium tuberculosis genotypes obtained from elderly Finns were assessed and compared with those obtained from younger Finns to comprehend the epidemiology of tuberculosis (TB) in Finland. From 2008 to 2011, a total of 1021 M. tuberculosis isolates were characterized by spoligotyping and 15-locus mycobacterial interspersed repetitive units-variable number tandem repeat typing. In total, 733 Finnish-born cases were included in the study, of which 466 (64%) were born before 1945 (older Finns). Of these, 63 (14%) shared an M. tuberculosis genotype with foreign-born or younger Finnish cases (born after 1945), and 59 (13%) shared a genotype with older Finnish cases. Eighty-five per cent had a unique genotypic profile while 70% belonged to T or Haarlem families, suggesting that ongoing transmission is infrequent among young and elderly Finns. Simultaneous reactivation of TB among older Finns was the most likely cause for clustering. As most isolates belonged to Haarlem or T, Finland was most likely affected by a similar TB epidemic at the beginning of the twentieth century as that seen in Sweden and Norway. Younger Finns were significantly more likely to be clustered (56% versus 27%, p<0.001), have pulmonary TB (87% versus 71%, p<0.001) and to be sputum smear positive (57% versus 48%, p<0.05) indicating that the risk of TB transmission from younger Finns is likely to be larger than from older Finns. The M. tuberculosis isolates from elderly Finns were associated with dominant lineages of the early twentieth century and differed from the heterogeneous lineages found among younger TB patients. Additionally, younger TB patients were more likely to transmit TB than elderly Finns.