Simo Nikkari

Centre for Biothreat Preparedness, Finland

Yersinia pseudotuberculosis is a Gram-negative intestinal pathogen of humans and has been responsible for several nationwide gastrointestinal outbreaks. Large-scale population genomic studies have been performed on the other human pathogenic species of the genus Yersinia, Yersinia pestis and Yersinia enterocolitica allowing a high-resolution unders...

This study investigated the presence of norovirus and adenovirus, especially enteric adenovirus, on the environmental surfaces (n = 481) and military conscripts’ hands (n = 109) in two Finnish garrisons (A and B) in 2013 and 2014. A questionnaire study was conducted to reveal possible correlations between viral findings on the conscripts’ hands and...

Voles (Arvicolinae, Rodentia) are known carriers of zoonotic bacteria such as Bartonella spp. and Francisella tularensis. However, apart from F. tularensis, the bacterial microbiome of voles has not previously been determined in Finland and rarely elsewhere. Therefore, we studied liver samples from 61 voles using 16S ribosomal RNA gene PCR analysis...

Bacillus spp. include human pathogens such as Bacillus anthracis, the causative agent of anthrax and a biothreat agent. Bacillus spp. form spores that are physically highly resistant and may remain active over sample handling. We tested four commercial DNA extraction kits (QIAamp DNA Mini Kit, RTP Pathogen Kit, ZR Fungal/ Bacterial DNA MiniPrep, an...

Technical Appendix.Diagnostic findings of patient, laboratory findings of sampling from rodents and environment, and images of progressive disease in eye of patient with ocular cowpox, Finland.

Although adenoviruses were identified as important respiratory pathogens many years ago, little information is available concerning the prevalence of different adenovirus serotypes, which are circulating and causing epidemics in Finnish military training centers. Over a period of five years from 2008 to 2012, 3577 respiratory specimens were collect...

Finland repeatedly reports some of the highest incidences of tularaemia worldwide. To determine genetic diversity of the aetiologic agent of tularaemia, Francisella tularensis, a total of 76 samples from humans (n = 15) and animals (n = 61) were analysed. We used CanSNPs and canINDEL hydrolysis or TaqMan MGB probes for the analyses, either directly...

The spread of infectious diseases is a global challenge. Timely identification of agents that cause outbreaks of infectious disease is vital in outbreak management by e.g. physical isolation of victims, and enables appropriate medical intervention with antibiotics and vaccines. Many of the emerging and re‐emerging infectious diseases as well as cla...

The CRISPR/Cas system is used by bacteria and archaea against invading conjugative plasmids or bacteriophages. Central to this immunity system are genomic CRISPR loci that contain fragments of invading DNA. These are maintained as spacers in the CRISPR loci between direct repeats and the spacer composition in any bacterium reflects its evolutionary...

Objectives/HypothesisTo provide information on the course of acute rhinosinusitis (ARS) with sequential nasal and paranasal microbiological data and their correlation with clinical outcomes. Study DesignWe conducted a prospective cohort study among 50 Finnish military recruits with clinically diagnosed ARS in spring 2012. Methods We collected sympt...

Tularemia outbreaks in humans have been linked to fluctuations in rodent population density, but the mode of bacterial maintenance in nature is unclear. Here we report on an experiment to investigate the pathogenesis of Francisella tularensis infection in wild rodents, and thereby assess their potential to spread the bacterium. We infected 20 field...

[Introduction: Centre for Military Medicine and University of Helsinki study together prevalence of enteric viruses, especially noroviruses, on surfaces and conscripts´ hands at both garrisons and field conditions. A questionnaire-based survey inquiring gastroenteritis symptoms is combined to the study. The project is related to field hygiene, envi...

Abstract Francisella tularensis is a highly virulent intracellular bacterium causing the zoonotic disease tularemia. It recurrently causes human and animal outbreaks in northern Europe, including Finland. Although F. tularensis infects several mammal species, only rodents and lagomorphs seem to have importance in its ecology. Peak densities of rode...

SUMMARY Few population-based data are available on factors associated with pneumonic and ulceroglandular type B tularaemia. We conducted a case-control study during a large epidemic in 2000. Laboratory-confirmed case patients were identified through active surveillance and matched control subjects (age, sex, residency) from the national population...

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Infectious agents have been suggested to be involved in atherosclerosis. By using a novel subtraction broad-range PCR approach, we defined bacterial DNA signatures in surgically removed sterile carotid artery endarterectomy plaques of patients with carotid atherosclerosis. Eighty partial bacterial 16S rDNA nucleotide sequences from eight patients w...

This article is an overview about medical logistics R&D in the Finnish Defence Forces. Article is written in Finnish.

The 9/11 terror attacks, followed by mailing of letters containing anthrax spores, changed our comprehension on threats towards modern society. Finland is committed by international treaties to develop biosafety and biosecurity legislation, and general awareness of the legislation. However, the rapidly developing field of biosciences cannot be exte...

Botulism is caused by botulinum neurotoxin produced by the bacterium Clostridium botulinum. It is a flaccid paralysis in which consciousness and nociception are preserved. Natural botulism typically results from ingestion of inadequately heated or unheated vacuum-packed foods. In addition, botulinum toxin is one of the most feared biological weapon...

Timely identification of respiratory pathogens is essential for appropriate patient care and cohorting. In order to do rapid identification-technology near the patient we utilized the field-deployable RAZOR EX-thermocycler with a reverse transcription real-time PCR assay that detects all subtypes of influenza A virus. In addition, we developed a RT...

Article reports on a general level how the CB defence unit of the Centre for Military Medicine provides support to occupational health and safety, especially at BSL-2/3 work and in the mobile diagnostic CBRN field laboratory of the Finnish Defence Forces.

Microbes and their toxins are biological weapons that can cause disease in humans, animals or plants, and which can be used with hostile intent in warfare and terrorism. Biological agents can be used as weapons of mass destruction and therefore, immense human and social and major economical damage can be caused. Rapid development of life sciences a...

The Finnish mobile diagnostic CBRN field laboratory represents Finnish design as its best: modern and compact functionality. The laboratory has been evaluated and approved by NATO, and it is ready to be used in a variety of defense purposes, including international crisis management. The laboratory comprises four separate modules, namely the labor...

Sindbis virus (SINV) is an arthropod-borne alphavirus found widely in Eurasia, Africa and Oceania. Clinical SINV infection, characterized by rash and arthritis, is reported primarily in Northern Europe. The laboratory diagnosis of SINV infection is based currently on serology. A one-step TaqMan(®) real-time RT-PCR assay was developed for the detect...

Clin Microbiol Infect 2011; 17: 34–43 Rapid detection is essential for timely initiation of medical post-exposure prophylactic measures in the event of intentional release of biological threat agents. We compared real-time PCR assay performance between the Applied Biosystems 7300/7500 and the RAZOR instruments for specific detection of the causativ...

In September 2009, an outbreak of 2009 pandemic influenza A(H1N1) took place in a Finnish garrison. In November 2009, we performed a serological survey among 984 recruits undergoing their military service at the garrison and related the results to self-reported upper respiratory tract infection (URTI) with or without fever. Of 346 volunteers who do...

A large sample of Finnish military conscripts of the armored brigade were questioned on the extent to which they trusted the information given biopreparedness authorities (such as the police, military, health care, and public health institutions) and how confident they were in the authority's ability to protect the public during a potential infecti...

The increased traveling to dengue endemic regions and the numerous epidemics have led to a rise in imported dengue. The laboratory diagnosis of acute dengue requires several types of tests and often paired samples are needed for obtaining reliable results. Although several diagnostic methods are available, proper comparative data on their performan...

We report a multiplatform real-time polymerase chain reaction methodology based on genes encoding for the regulatory toxR activator and enterotoxin A protein to determine enterotoxigenic Vibrio cholerae types from other vibrios. This assay, which was successfully validated on a collection of 87 bacterial strains, including 63 representatives of V....

All patients treated in 1978-1982 for the first time as in-patients at our hospital for arthritis following a gastrointestinal or an urogenital infection were reviewed. Of 216 patients initially diagnosed as either enteroarthritis or uroarthritis, 74 were retrospectively disqualified, chiefly because of insufficient documentation of the preceding i...

Yersinia pestis (Y. pestis) is a zoonotic bacterium mainly circulating among rodents and their fleas. Transmission to humans can cause bubonic, pneumonic or septicemic plague with a high case-fatality rate. Therefore, rapid and reliable diagnostic tools are crucial. The objective of this study was to assess the inter-laboratory reproducibility of i...

Various studies have suggested the involvement of infectious agents in chronic inflammatory diseases, including atherosclerosis. By using a novel subtraction broad-range PCR approach, we defined bacterial DNA signatures in surgically removed sterile abdominal aorta samples of patients with aortic atherosclerosis. Partial bacterial 16S rDNA nucleoti...

Dynamics of bacteria during acute otitis media (AOM) has not been thoroughly studied because it requires repeated tympanocentesis. AOM with tympanostomy tube otorrhea provides a unique opportunity to study the appearance and disappearance of pathogens during the course of the disease without stressing the child. Middle ear fluid (MEF) samples were...

This report describes the development of in-house real-time PCR assays using minor groove binding probes for simultaneous detection of the Bacillus anthracis pag and cap genes, the Francisella tularensis 23 KDa gene, as well as the Yersinia pestis pla gene. The sensitivities of these assays were at least 1 fg, except for the assay targeting the Bac...

Bacteria are found in 50%-90% of cases of acute otitis media (AOM) with or without otorrhea, and viruses are found in 20%-49% of cases. However, for at least 15% of patients with AOM, the microbiological etiology is never determined. Our aim was to specify the full etiology of acute middle ear infection by using modern microbiological methods conco...

The aetiology of infective endocarditis (IE) can be determined directly from surgically removed valve tissue using broad-range bacterial rDNA polymerase chain reaction (PCR) followed by sequencing. We sought to assess the value of this methodology in a routine clinical setting. Broad-range PCR with primers targeting conserved bacterial rDNA sequenc...

We report a fatal case of severe immunodeficiency associated with infection caused by the white rot fungus, Merulius tremellosus. This is the first report of Merulius tremellosus infection in humans. To improve clinical management, awareness and diagnostics of uncommon fungal infections in immunodeficient patients are important.

We developed a diagnostic array of oligonucleotide probes targeting species-specific variable regions of the genes encoding topoisomerases GyrB and ParE of respiratory bacterial pathogens. Suitable broad-range primer sequences were designed based on alignment of gyrB/parE sequences from nine different bacterial species. These species included Coryn...

To evaluate the usefulness of the broad range bacterial rDNA polymerase chain reaction (PCR) method combined with DNA sequencing in the aetiological diagnosis of intracranial or spinal infections in neurosurgical patients. In addition to conventional methods, the broad range bacterial PCR approach was applied to examine pus or tissue specimens from...

The etiology of chronic urticaria is undefined, but the potential role of infectious agents as one triggering factor has been suggested. The appearance of chronic urticaria in a 16-year old male after a history of a recent parvovirus B19 (B19) infection led us to investigate the association between B19 and chronic urticaria. To investigate whether...

Population-based surveillance for unexplained death and critical illness possibly due to infectious causes (UNEX) was conducted in four U.S. Emerging Infections Program sites (population 7.7 million) from May 1, 1995, to December 31, 1998, to define the incidence, epidemiologic features, and etiology of this syndrome. A case was defined as death or...

Broad-range rDNA polymerase chain reaction (PCR) provides an alternative, cultivation-independent approach for identifying pathogens. In 1995, the Centers for Disease Control and Prevention initiated population-based surveillance for unexplained life-threatening infections (Unexplained Death and Critical Illness Project [UNEX]). To address the caus...

Culture-negative bacterial endocarditis may be attributed to fastidious microorganisms, prior institution of antibiotic treatment, or both. We describe a case of culture-negative endocarditis in which a modified Steiner stain revealed bacterial structures in the resected heart valve material. Prompted by this finding, broad-range polymerase chain r...

To assess the presence of circulating IgA and IgG antibodies to Chlamydia trachomatis in sera of patients with reactive arthritis (ReA) and other arthritides. A peptide based enzyme immunoassay (EIA) was used to study 132 patients divided into 5 groups: C. trachomatis triggered ReA, uroarthritis, enteroarthritis, oligoarthritis, and rheumatoid arth...

Real-time PCR methods with primers and a probe targeting conserved regions of the bacterial 16S ribosomal DNA (rDNA) revealed a larger amount of rDNA in blood specimens from healthy individuals than in matched reagent controls. However, the origins and identities of these blood-associated bacterial rDNA sequences remain obscure.

Decorin is a small extracellular chondroitin/dermatan sulfate proteoglycan that has previously been shown to be involved in the angiogenesis-like behavior of endothelial cells (ECs) in vitro. There is also evidence that decorin plays a role in angiogenesis in vivo. In this study we sought to further explore the involvement of decorin in angiogenesi...

To examine the prevalence, binding sites and functional interactions of antineutrophil cytoplasmic autoantibodies (ANCA) against the bactericidal/permeability increasing protein (BPI) in reactive arthritis (ReA). Sera were analysed for the occurrence of ANCA by indirect immunofluorescence microscopy (IIF) and ELISA. Binding sites were determined us...

A broad-range bacterial PCR targeting rRNA genes (rDNAs) was used to directly analyze 536 clinical samples obtained from 459 hospitalized patients during a 4-year study period. The molecular diagnosis based on DNA sequencing of the PCR product was compared to that obtained by bacterial culture. The bacteriological diagnosis was concordant for 447 (...

We investigated a patient with Salmonella infantis triggered reactive arthritis (ReA) for a possible occurrence of S. infantis-specific antigens and DNA in the synovial fluid (SF) cells. S. infantis-specific antigens were abundantly observed by immunofluorescence in SF cells of the patient during acute joint inflammation. Salmonella-specific DNA wa...

Blood-based pneumolysin PCR was compared to blood culture and detection of pneumolysin immune complexes, as well as to detection of antibodies to pneumolysin and to C polysaccharide, in the diagnosis of pneumococcal infection in 75 febrile children. Invasive pneumococcal infection was suspected on clinical grounds in 67 of the febrile children, and...

Blood-based pneumolysin PCR was compared to blood culture and detection of pneumolysin immune complexes, as well as to detection of antibodies to pneumolysin and to C polysaccharide, in the diagnosis of pneumococcal infection in 75 febrile children. Invasive pneumococcal infection was suspected on clinical grounds in 67 of the febrile children, and...

The primary symptoms of many vasculitides resemble those of infectious diseases. Patients with Wegener's granulomatosis usually seek medical care for respiratory tract symptoms resembling those caused by infection or allergy. In addition, vasculitis is a well-documented manifestation of infection by some known microbial agents. There have been rela...

Signaling lymphocytic activation molecule (SLAM) is a novel glycoprotein expressed on activated T and B cells. Ligation of cell surface SLAM, either by anti-SLAM mAbs or the recombinant soluble form of SLAM (sSLAM), enhanced the proliferation of T and B cells in vitro. In addition, the engagement of SLAM on T cells preferentially induced IFN-gamma...

Objective To investigate whether microbial components are present in the cells of synovial fluid or peripheral blood from patients with Salmonella-triggered reactive arthritis (ReA).Methods Synovial fluid cells and/or peripheral blood cells from 23 patients with Salmonella-triggered ReA and from 19 control patients with newly diagnosed rheumatoid a...

We evaluated a commercial immunoglobulin M (IgM)-capture immunoassay for the detection of Mycoplasma pneumoniae infections in 278 pediatric patients with community-acquired, radiographically defined pneumonia. Acute- and convalescent-phase serum samples were collected from all patients and were tested for M. pneumoniae-specific IgM and IgG antibodi...

Recently, we have shown that the tumor necrosis factor-alpha (TNF-alpha)-induced morphological change of EA.hy 926 human endothelial cells is associated with a decrease in the net synthesis of two proteoglycans (PGs), biglycan and syndecan-1, both of which have been suggested to play a role in cell adhesion. Here we have examined whether this pheno...

We used broad-range bacterial PCR combined with DNA sequencing to examine prospectively cerebrospinal fluid (CSF) samples from patients with suspected meningitis. Fifty-six CSF samples from 46 patients were studied during the year 1995. Genes coding for bacterial 16S and/or 23S rRNA genes could be amplified from the CSF samples from five patients w...

The intimal hyperplasia hypothesis that equates lumen narrowing after arterial injury with intimal mass has recently been challenged. Evidence has emerged to suggest that lumen narrowing is caused in large part by changes in artery wall geometry rather than intimal mass per se. We have begun to explore this hypothesis in a unique nonhuman primate m...

The distributions of versican, biglycan, and decorin have been examined in segments of normal and atherosclerotic human coronary arteries using antibodies directed against the core proteins of these macromolecules. Versican immunostaining was prominent throughout the extracellular matrix (ECM) in regions of the vessels that contained abundant smoot...

Synovial fluid cells from 12 patients with reactive arthritis (ReA) triggered by Chlamydia trachomatis were studied for the presence of Chlamydia DNA using the ligase chain reaction (LCR) LCx (Abbott) and the polymerase chain reaction (PCR) Amplicor (Roche). In addition, peripheral blood leucocytes from 11 of these patients were analysed by LCR. As...

To determine, by studying patients with early rheumatoid arthritis (RA), whether rubella virus (rubella), mumps virus (mumps), or measles virus (measles) plays a role in the pathogenesis of RA. Polymerase chain reaction combined with reverse transcription was used to detect viral RNA in peripheral blood mononuclear cells (PBMC) or synovial fluid (S...

To study HLA class II association in reactive arthritis. 63 patients with reactive arthritis and 46 with rheumatoid arthritis were included in the study. HLA-DR alleles were determined by using a sequence specific PCR method. Oligonucleotide hybridisation was used for definition of DRB1*04 subtypes and DQB1 alleles. HLA-B27 was determined by standa...

A previously healthy 33-year-old male patient presented with fever, rash and polyarthritis. Subsequently, he developed pleuropneumonitis, pericardial effusion and hepatitis. The diagnosis of parvovirus B19 infection was based on the detection of parvovirus DNA by PCR in a skin biopsy, bone marrow cells and serum. The patient had high parvovirus IgG...

Since April 1993 in Finland and March 1994 in Switzerland, polymerase chain reaction (PCR) has been used routinely nationwide for the diagnosis of pertussis. Nasopharyngeal specimens from 3794 patients suspected of having pertussis and 1125controls were tested. Finnish and Swiss assays found 23% and 36% of clinical specimens positive, respectively....