Lessons learned from 2001-2021 - from the bioterrorism to the pandemic era.

INTRODUCTION AND OBJECTIVE: The aim of the study was to analyze available literature on the development of biological warfare and combating the SARS CoV-2 pandemic. Against the background of contemporary threats from biological factors, the strengths and weaknesses of response in the event of a bioterrorist attack during the ongoing COVID-19 pandemic have been identified. The scope and importance of international cooperation in the fight against the pandemic is assessed. REVIEW METHODS: The more important literature on bioterrorism, biological weapons and the COVID-19 pandemic, both from earlier work and recent publications, was analyzed, emphasizing new threats and adequate defence against them. BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: The bio-warfare threat and the current COVID 19 pandemic that has hit mankind on a global scale has clearly shown how dangerous biological agents are and what effects they can cause, negatively affecting every sphere of human activity with catastrophic consequences. Data on examples of bioterrorist attacks carried out and research on the development of biological weapons and methods of combating pandemic COVID-19, were reviewed. New threats related to technological development,including those resulting from genetic manipulation, biosynthesis, and modern means of delivery, are pointed out. Attention has been paid to the implications of controlling the proliferation of biological weapons and the issues of international cooperation in the fight against bioterrorism and the COVD-19 pandemic. SUMMARY: The lesson learned clearly demonstrates the weakness of states in responding to such threats. The risks of uncontrolled scientific advances are still underestimated. Appropriate international control measures must be taken urgently to prepare for new pandemics, bioterrorist attacks, and the possibility of using modern biological weapons.

80 Years of the Medicine and Tropical Hygiene Center in Gdynia (1937-2017): The Pioneer Pre-War Years 1937-1939.

The present Interdepartmental Institute of Maritime and Tropical Medicine in Gdynia of the Medical University of Gdansk was formally established in 1939 by the Order of June 5, 1939, of the Minister of Social Welfare, Marian Zyndram-Koscialkowski. However, the Branch of the National Institute of Hygiene in Gdynia was founded 2 years earlier, in 1937 (the first head was Dr. Med. Jerzy Jakóbkiewicz [1892-1953]), and its fruitful activity was ennobled 2 years later by increasing its rank and adding the name "Marine and Tropical Hygiene Institute". These facts are very little known, and therefore worth presenting in the jubilee years of the 80th anniversary of the institution.

Solec Spa - worldwide unique properties of Polish health resort in the service of rural medicine.

Solec Spa is health resort in south-eastern Poland. Its unique balneorehabilitation significance worldwide is determined by chloride-iodine-sodium water with a high content of hydrogen sulphide. This water, classified as highly mineralized sodium-chloride (seltzer) sulphide, bromide, iodide, boron water, contains naturally approximately 0.9 g/l divalent sulphur compounds, which is the highest concentration noted among the mineral waters of the world. The effectiveness of the Solec waters is proven in: inflammatory and autoimmunological locomotor system diseases, degenerative joint disorders (osteoarthritis), post-traumatic and post-operative orthopedic diseases, skin diseases and allergic disorders. One of the main indications for balneotherapy in Solec Spa and Busko Spa is chronic brucellosis.

Evolution of sanitary-epidemiological services in Poland in the years 1944-2014.

This paper presents the history of sanitary-epidemiological services in the context of the health, economic and socio-political situation in Poland in the years 1944-2014, with a critical analysis of legal restraints, efficiency and achievements. Polish Sanitary Services, established in 1919, as a state service, have preserved for more than 95 years (also during World War II and the occupation) the continuity of its structures and essential objectives to enable their implementation in the field of public health protection. The unique effectiveness of actions was recorded in the years 1954-1998 and 2002-2009 in the time of central (vertical) subordination of sanitary-epidemiological services. The pre-accession preparation to the European Union (EU) strongly accelerated the development of sanitary-epidemiological services in Poland. Polish accession to the European Union has promoted the implementation of the WHO document "Health for All in the 21st Century" and the reduction of "health inequalities".

The Lethal Spanish Influenza Pandemic in Poland.

The Spanish influenza pandemic in the years 1918-1920 was the largest and most tragic pandemic of infectious disease in human history. Deciphering the structure of the virus (including the determination of complete genome sequence) of this pandemic and the phylogenetic analysis and explanation of its virulence became possible thanks to molecular genetic analysis of the virus isolated from the fixed and frozen lung tissue of influenza victims who died in 1918 and were buried frozen in Alaska and Spitsbergen. Epidemiological data from the course of this pandemic in Poland have not been previously published. For analysis, we used source materials such as clinical studies and case reports of doctors fighting against the pandemic and registries of influenza cases in units of the Polish Army and military hospitals. Clinically, the pandemic of 1918 was characterized by the same symptoms and course as influenza in other years. Pathologically, the disease was similar to the other pandemic, in that the destruction was mostly limited to the respiratory tract. The "Spanish" influenza pandemic of 1918-1920 took place in Poland in 3 epidemic waves. The peaks of morbidity and mortality occurred in the capital, Warsaw, in December 1918 and in December 1919 to January 1920. It is estimated that throughout the pandemic period of 1918-1920 in Poland, 200 000 to 300 000 people died.

[Pappataci (sandfly fever) - a little known brought in Poland viral disease]. / Goraczka pappataci (sandfly fever) ­ malo znana w Polsce choroba wirusowa przywlekana do kraju.

Pappataci (sandfly fever) is a viral (RNA Phlebovirus) vector-borne zoonosis transmitted to men by small Phlebotomus mosquitous. This disease fulfill the international criteria of "emerging disease". Despite of that, pappataci fever is a little known disease brought into Poland. Distribution of disease includes: Mediterranean region, Central Asia and Indian Peninsula. On the basis of pertinent literature and own personal experience, the authors described etiopathogenesis, epidemiology and clinical picture of sandfly fever.

Epidemiological analysis of diseases of children and adolescents requiring neurological and mobility rehabilitation in the Swietokrzyskie Rehabilitation Center in Czarniecka Góra, Poland.

INTRODUCTION AND OBJECTIVE: Epidemiological analysis of the dynamics of admissions and patient characteristics is presented concerning 5,955 children and adolescents (3-18 years of age) hospitalized in 2007-2013 with neurological and mobility diseases in Swietokrzyskie Rehabilitation Centre (SRC) in southern Poland. MATERIALS AND METHOD: Within the period of 7 years, 18,647 patients were admitted to the SRC, of whom 9,546 were admitted to the daily ward and 9,109 to the stationary wards. 5,955 were children and adolescents aged 3-18, 1,499 were children aged 3-13 and almost three times more were patients aged 14-18. The correlation between the number of admissions in each year and the number of those hospitalized depending on the age and diagnosis was examined. RESULTS: In the discussed period, in both age ranges, the group of deforming dorsopathies dominated, while cerebral palsy was the second most common cause of hospitalization, and the and post-traumatic disorder the smallest number. In the diagnoses of cerebral palsy and post-traumatic disease, boys constituted most of the hospitalized. In contrast, girls dominated in the group of deforming dorsopathies. DISCUSSION: Analysis of the material of 5,955 patients revealed a number of quantitative data which assisted in the analysis of the epidemiological situation of this group of diseases - necessary for the planning of highly specialized treatment and rehabilitation. The greatest needs in terms of admissions to the SRC concerned the group of adolescents aged 14-18. The results of combined rehabilitation indicated the full use of places in the Swietokrzyskie Rehabilitation Center and also indicated the need for similar provincial and even regional centres.

Bacillus anthracis infections--new possibilities of treatment.

INTRODUCTION AND OBJECTIVE: Bacillus anthracis is one of biological agents which may be used in bioterrorism attacks. The aim of this study a review of the new treatment possibilities of anthrax, with particular emphasis on the treatment of pulmonary anthrax. Abbreviated description of the state of knowledge. Pulmonary anthrax, as the most dangerous clinical form of the disease, is also extremely difficult to treat. Recently, considerable progress in finding new drugs and suitable therapy for anthrax has been achieved, for example, new antibiotics worth to mentioning, levofloxacin, daptomycin, gatifloxacin and dalbavancin. However, alternative therapeutic options should also be considered, among them the antimicrobial peptides, characterized by lack of inducible mechanisms of pathogen resistance. Very promising research considers bacteriophages lytic enzymes against selected bacteria species, including antibiotic-resistant strains. RESULTS: Interesting results were obtained using monoclonal antibodies: raxibacumab, cAb29 or cocktails of antibodies. The application of CpG oligodeoxynucleotides to boost the immune response elicited by Anthrax Vaccine Adsorbed and CMG2 protein complexes, also produced satisfying therapy results. Furthermore, the IFN-α and IFN-ß, PA-dominant negative mutant, human inter-alpha inhibitor proteins and LF inhibitors in combination with ciprofloxacin, also showed very promising results. CONCLUSIONS: Recently, progress has been achieved in inhalation anthrax treatment. The most promising new possibilities include: new antibiotics, peptides and bacteriophages enzymes, monoclonal antibodies, antigen PA mutants, and inter alpha inhibitors applications. In the case of the possibility of bioterrorist attacks, the examination of inhalation anthrax treatment should be intensively continued.

Prevalence of Coxiella burnetii Infection in Humans Occupationally Exposed to Animals in Poland.

Coxiella burnetii is the etiological agent of Q fever, and outbreaks of Q fever have been reported in different parts of Europe both in animals and humans. Human infections are mostly associated with infections in ruminants, e.g., sheep, goats, and cows. Various professional groups are occupationally exposed to infection with C. burnetii. The aim of this study was investigate the prevalence of C. burnetii in farm workers. Serum samples were collected from 151 persons from six different regions of Poland. The serum samples were tested using three serological methods--complement fixation test (CFT), enzyme-linked immunosorbent assay (ELISA), and indirect fluorescent antibody (IFA). A total of 71 samples of blood were also tested by real-time PCR. The results showed that antibodies against C. burnetii were present in the tested sera. Average percentages of seropositive samples in IFA, ELISA, and CFT were 31.12%, 39.07%, and 15.23%, respectively. Positive results were noted in each testing center. Of the three test types, IFA results were considered the most sensitive. Real-time PCR confirmed the presence of DNA specific for C. burnetii in 10 patients. The farming workforce constitutes an occupational risk group with an increased risk for C. burnetii infection, presumably because of their contact with infected livestock.

Prevalence of Coxiella burnetii in environmental samples collected from cattle farms in Eastern and Central Poland (2011-2012).

Coxiella burnetii is the etiologic agent of Q fever. It may occur as two different morphological forms, a large cell variant (LCV) and a small cell variant (SCV). The SCV is characterized by unique resistance to physical and chemical factors and may survive in the environment for many months. The objective of this study was to examine environmental samples for the presence of C. burnetii using real-time PCR in areas where Q fever was previously reported and in randomly selected animal farms where Q fever was not reported. The samples were collected in the following provinces in Poland: Lublin, Subcarpathian and Masovian. Monitoring was performed with real-time PCR and serological methods. Of the 727 environmental samples, 33 (4.54%) contained the multi-copy insertion sequence IS1111, which is specific for C. burnetii. Subsequently, the presence of C. burnetii antibodies was determined using serological tests in selected herds in which positive genetic results were obtained. Serological analyses of 169 serum samples using CFT and ELISA were performed on Polish black-and-white Holstein-Friesian cows and one cow imported from Denmark. Using the CFT method, 11 samples were positive for phase I antibodies and six were positive for phase II antibodies. Moreover, in two cases, the presence of antibodies specific for both phase I and phase II antigens of C. burnetii was detected. However, of the 169 examined serum samples, 20 were positive by ELISA test, of which six were also positive by CFT. Additionally, multi spacer typing (MST) of isolated C. burnetii strains was performed. The MST results identified two new genotypes in Poland, ST3 and ST6. The results indicate that continued research regarding spread of this pathogen within a country is necessary.

Hantavirus RNA was not detected in Dermacentor reticulatus ticks.

A total of 190 Dermacentor reticulatus ticks (80 males, 110 females) collected on the territory of Ostrów Lubelski, Suchawa, Zalutyn and Kazimierz Dolny (Lublin Province, eastern Poland) were examined by reverse transcription PCR and nested PCR methods for the presence of hantavirus RNA. None of the examined Dermacentor reticulatus specimens showed the presence of the hantavirus-specific RNA in spite of using two pairs of primers and the clearly positive results obtained with the positive control. Thus, the hypothesis about the possible participation of ticks in the transmission of hantaviruses was not confirmed.

Q fever--selected issues.

Q fever is an infectious disease of humans and animals caused by Gram-negative coccobacillus Coxiella burnetii, belonging to the Legionellales order, Coxiellaceae family. The presented study compares selected features of the bacteria genome, including chromosome and plasmids QpH1, QpRS, QpDG and QpDV. The pathomechanism of infection--starting from internalization of the bacteria to its release from infected cell are thoroughly described. The drugs of choice for the treatment of acute Q fever are tetracyclines, macrolides and quinolones. Some other antimicrobials are also active against C. burnetii, namely, telitromycines and tigecyclines (glicylcycline). Q-VAX vaccine induces strong and long-term immunity in humans. Coxevac vaccine for goat and sheep can reduce the number of infections and abortions, as well as decrease the environmental transmission of the pathogen. Using the microarrays technique, about 50 proteins has been identified which could be used in the future for the production of vaccine against Q fever. The routine method of C. burnetii culture is proliferation within cell lines; however, an artificial culture medium has recently been developed. The growth of bacteria in a reduced oxygen (2.5%) atmosphere was obtained after just 6 days. In serology, using the IF method as positive titers, the IgM antibody level >1:64 and IgG antibody level >1:256 (against II phase antigens) has been considered. In molecular diagnostics of C. burnetii infection, the most frequently used method is PCR and its modifications; namely, nested PCR and real time PCR which detect target sequences, such as htpAB and IS1111, chromosome genes (com1), genes specific for different types of plasmids and transposase genes. Although Q fever was diagnosed in Poland in 1956, the data about the occurrence of the disease are incomplete. Comprehensive studies on the current status of Q fever in Poland, with special focus on pathogen reservoirs and vectors, the sources of infection and molecular characteristics of bacteria should be conducted.

A small-scale survey of hantavirus in mammals from eastern Poland.

Samples of 30 dead small mammals each were collected on area 'A' located in eastern Poland which is exposed to flooding by the Vistula river, and on the area 'B', also located in eastern Poland but not exposed to flooding. Kidneys and livers of the mammals were examined by the PCR and nested PCR methods for the presence of hantavirus RNA. Out of 7 species of small mammals examined, the presence of hantaviruses was detected in 4 of them. Hantavirus prevalence was low in Apodemus agrarius (2.6%), the most numerous mammal species, whereas in the remaining 3 positive species (Microtus agrestis, Myodes glareolus, Sorex araneus) this was 12.5-100%. The presence of hantaviruses was detected only in the animals found on area 'A' exposed to flooding, and their prevalence was statistically greater compared to area 'B' not exposed to flooding (16.7% vs. 0%, p=0.0345). The overall positivity of the examined small mammals population from the areas 'A' and 'B' was 8.3%. The sequence analysis of the samples positive for hantavirus proved that the amplified products showed 77-86% homology with the L segment sequence of hantavirus Fusong-Mf-731 isolated from Microtus fortis in China. The presented study is the first to demonstrate the occurrence of hantavirus infection in small mammals from eastern Poland, and the first to demonstrate the significant relationship between flooding and the prevalence of hantaviruses in small mammals.

Research on substances with activity against orthopoxviruses.

Although smallpox was eradicated over 30 years ago, the disease remains a major threat. High mortality, high infectivity and low resistance of the contemporary population make the smallpox virus very attractive to terrorists. The possible presence of illegal stocks of the virus or risk of deliberate genetic modifications cause serious concerns among experts. Hence, it is reasonable to seek effective drugs that could be used in case of smallpox outbreak. This paper reviews studies on compounds with proven in vitro or in vivo antipoxviruses potential, which show various mechanisms of action. Nucleoside analogues, such as cidofovir, can inhibit virus replication. Cidofovir derivatives are developed to improve the bioavailability of the drug. Among the nucleoside analogues under current investigation are: ANO (adenozine N1-oxide) and its derivatives, N-methanocarbothymidine [(N)-MCT], or derivatitives of aciklovir, peninclovir and brivudin. Recently, ST-246 - which effectively inhibits infection by limiting release of progeny virions - has become an object of attention. It has been also been demonstrated that compounds such as: nigericin, aptamers and peptides may have antiviral potential. An interesting strategy to fight infections was presented in experiments aimed at defining the role of individual genes (E3L, K3L or C6L) in the pathogenesis, and looking for their potential blockers. Additionally, among substances considered to be effective in the treatment of smallpox cases, there are factors that can block viral inhibitors of the human complement system, epidermal growth factor inhibitors or immunomodulators. Further studies on compounds with activity against poxviruses are necessary in order to broaden the pool of available means that could be used in the case of a new outbreak of smallpox.

Human alveolar echinococcosis in Poland: 1990-2011.

BACKGROUND: Alveolar echinococcosis (AE) caused by Echinococcus multilocularis infections is a dangerous old disease in the Northern Hemisphere. The aim of the paper was to collect and analyze data on human AE in Poland in the last two decades. METHODOLOGY/PRINCIPAL FINDINGS: The sources of data were both the cases officially registered and detected by an active field and laboratory surveillance. The cases were verified by clinical, epidemiological, and laboratory criteria. Altogether 121 human cases of AE were detected. Among these 83 (68,6%) cases were classified as confirmed, 16 as probable and 22 as possible. During the two decades a continuous increase in detection rate was noticed. The cases were 6-82 years old at the time of diagnosis (mean - 47.7 years). Sex ratio M/F was 0.86/1.0. The AE was fatal in 23 (19%) patients (mean age at death - 54.1 years). Family agglomeration of AE was found in 4 foci, involving 9 patients. Seventy six of the cases were diagnosed in an advanced stage of disease. In all cases the liver was the primary location of AE. In 30 (24.8%) patients a spread to other organs was observed. Ninety four of the patients were treated with albendazole. In 73 (60%) patients a surgical operation was performed, including 15 liver transplantations. CONCLUSIONS/SIGNIFICANCE: The studies confirmed that AE is an emerging disease in Poland, which is the fourth country in Europe with over 120 cases detected. The results also indicate the need of a wider national programme for implementation of screening in the highest AE risk areas (north-eastern Poland) with an effort to increase the public awareness of the possibility of contracting E. multilocularis, and above all, training of the primary care physicians in the recognition of the risk of AE to allow for an early detection of this dangerous disease.

Research on prevention and treatment of hemorrhagic fevers.

Viral hemorrhagic fevers are severe zoonotic diseases caused by RNA-viruses classified into 4 families: Arenaviridae, Bunyaviridae, Filoviridae, and Flaviviridae. They are present on all continents except Antarctica, their person-to-person spread is easy, and there is a high risk of them being used as weapon by bioterrorists. So far, efforts to develop effective drugs against these viruses have failed, and typical therapy usually relies on symptomatic treatment. Search for substances that could effectively inhibit this type of infections is now a priority. The presented paper gives an overview of different approaches used in combating the viral hemorrhagic fevers. Researchers look for safe antiviral agents with appropriate properties among natural sources, such as various types of herbs plants, algae, or essential oils obtained from trees, as well as investigate the use of various synthetic substances. The aim is to broaden the pool of available antiviral drugs that could replace hitherto applied medicines such as ribavirin, which is not always sufficiently effective and may have side-effects. The scientists focus not only on combating the diseases, but also on their prevention. For this purpose, recombinant vaccines or various types of immunomodulators may serve as a useful tools. Results of the latest studies are promising and encourage further work which may eventually lead to the solution of the urgent problem of hemorrhagic fevers.

Seroprevalence of leptospirosis in rural populations inhabiting areas exposed and not exposed to floods in eastern Poland.

Blood serum samples collected from randomly selected groups of 100 persons inhabiting rural community 'A' located in eastern Poland and exposed to floods by the Vistula river, and 98 persons inhabiting rural community 'B', also located in eastern Poland, but in the area not exposed to floods were examined by the microscopic agglutination test (MAT) for the presence of antibodies against 18 Leptospira serovars. Positive results showed 3% of serum samples collected from community 'A', while the seroprevalence in community 'B' was 9.2%, being insignificantly higher than in community 'A'. For both examined communities (n=198), a significant positive correlation was found between the prevalence and titer of seropositive response and age of examined people (r=0.145, p=0.042). No significant differences were found between the prevalence of positive reactions in males and females (p>0.05). The reactions with 10 serovars of Leptospira (Australis, Autumnalis, Hebdomadis, Hardjo, Sejroe, Zanoni, Bataviae, Bratislava, Canicola and Grippotyphosa), belonging to 3 species (L. interrogans, L. borgpetersenii, L. kirschneri), were found in the examined communities. From both communities, of 12 persons demonstrating positive results in MAT, 9 showed reaction with one serovar, 2 with two serovars and 1 with three serovars. The highest titers found during the examination did not exceeded 800. In conclusion, our results suggest that there is only a slight, if any, hazard of an leptospirosis epidemic after the flood that afflicted eastern Poland in the year 2010 and the general epidemiological situation of leptospirosis in eastern Poland. Although there does not seem to be any cause for concern, further research is needed.

[Reform of epidemiology undergraduate education programme for Polish medical students--the changes threatening essentials of education in medical reasoning]. / Reforma nauczania epidemiologii studentów medycyny w Polsce--zmiana zagrazajaca nauczaniu podstaw rozumowania lekarskiego.

A concise account has been given of the changes included in the contents, shape and volume of the teaching program of epidemiology included in the current abridged set of proposals of the graduate teaching of the subject. The present slashed set of teaching items gives no real possibility of covering even the shortest agenda or either methodological or natural history oriented parts of epidemiological essentials. Given that epidemiological methodology is increasingly the part and parcel of the modern medical thinking in general, the shape of the reform is the dangerous step back against prevailing scientific currents threatening the very status of the national scientific institutions. The article is expected to find approval among university teachers of epidemiology facing the hard times of being obliged to teach or otherwise difficult and demanding subject.

Hantavirus RNA not detected in Ixodes ricinus ticks.

A total of 174 unfed Ixodes ricinus ticks (104 nymphs, 36 males, and 34 females) collected in the Roztocze National Park in eastern Poland were examined by the PCR and nested PCR methods for the presence of hantavirus RNA. None of the examined Ixodes ricinus specimens showed the presence of the hantavirus-specific RNA, in spite of using 2 genetic markers and the clearly positive results obtained with the positive control. Thus, a hypothesis about the possible participation of ticks in the transmission of hantaviruses, has so far not been confirmed.

[Management in Chikungunya virus infection--a new threat for Europe]. / Postepowanie w przypadku podejrzenia zakazenia wirusem Chikungunya--nowego zagrozenia dla Europy.

The authors present etiology, epidemiology and clinical aspects of one of the tropical diseases--Chikungunya fever (CHIK), which has spread across Europe as emerging infectious disease, transmitted to humans by Aedes mosquitoes. The aim of this study is to present the real threat of CHIK to Europe and especially to Poland. The article also describes actions taken by sanitary authorities in the European Union countries. It focused on the initiatives taken by the State Sanitary Inspection in order to prevent of CHIK and its vector. The article is based on the experience gained by a team from the Chief Sanitary Inspectorate. In conclusion the article describes information related to the occurrence of Chikungunya fever in Europe. Finally, it underlines the necessity of preventive measures too.